@article {pmid32975612,
year = {2020},
author = {Yoshida, Y and Matsumoto, I and Tanaka, T and Yamao, K and Hayashi, A and Kamei, K and Satoi, S and Takebe, A and Nakai, T and Takenaka, M and Takeyama, Y},
title = {Pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct leading to pancreatic pleural effusion: a case report.},
journal = {Surgical case reports},
volume = {6},
number = {1},
pages = {222},
doi = {10.1186/s40792-020-00987-7},
pmid = {32975612},
issn = {2198-7793},
abstract = {BACKGROUND: Pancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion.

CASE PRESENTATION: A 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854 IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15 × 15 mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor.

CONCLUSIONS: Differential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.},
}

@article {pmid31529566,
year = {2019},
author = {van Kooten, XF and Petrini, LFT and Kashyap, A and Voith von Voithenberg, L and Bercovici, M and Kaigala, GV},
title = {Spatially Resolved Genetic Analysis of Tissue Sections Enabled by Microscale Flow Confinement Retrieval and Isotachophoretic Purification.},
journal = {Angewandte Chemie (International ed. in English)},
volume = {58},
number = {43},
pages = {15259-15262},
doi = {10.1002/anie.201907150},
pmid = {31529566},
issn = {1521-3773},
support = {607322//FP7 People: Marie-Curie Actions/International ; 727761//H2020 European Research Council/International ; },
mesh = {Breast Neoplasms/*genetics/pathology ; DNA, Neoplasm/analysis/metabolism ; Female ; Formaldehyde/chemistry ; Genotype ; Humans ; MCF-7 Cells ; Microscopy, Confocal ; Paraffin Embedding ; Point Mutation ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Proto-Oncogene Proteins p21(ras)/*genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; },
abstract = {We have developed a method for spatially resolved genetic analysis of formalin-fixed paraffin-embedded (FFPE) cell block and tissue sections. This method involves local sampling using hydrodynamic flow confinement of a lysis buffer, followed by electrokinetic purification of nucleic acids from the sampled lysate. We characterized the method by locally sampling an array of points with a circa 200 μm diameter footprint, enabling the detection of single KRAS and BRAF point mutations in small populations of RKO and MCF-7 FFPE cell blocks. To illustrate the utility of this approach for genetic analysis, we demonstrate spatially resolved genotyping of FFPE sections of human breast invasive ductal carcinoma.},
}

Breast Neoplasms/*genetics/pathology
DNA, Neoplasm/analysis/metabolism
Female
Formaldehyde/chemistry
Genotype
Humans
MCF-7 Cells
Microscopy, Confocal
Paraffin Embedding
Point Mutation
Proto-Oncogene Proteins B-raf/*genetics/metabolism
Proto-Oncogene Proteins p21(ras)/*genetics/metabolism
Real-Time Polymerase Chain Reaction
Sequence Analysis, DNA

@article {pmid30842485,
year = {2019},
author = {Rossi, A and Dupaty, L and Aillot, L and Zhang, L and Gallien, C and Hallek, M and Odenthal, M and Adriouch, S and Salvetti, A and Büning, H},
title = {Vector uncoating limits adeno-associated viral vector-mediated transduction of human dendritic cells and vector immunogenicity.},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {3631},
pmid = {30842485},
issn = {2045-2322},
mesh = {Animals ; CD8-Positive T-Lymphocytes/immunology/virology ; Capsid/*immunology ; Capsid Proteins/*immunology ; Dendritic Cells/*immunology/virology ; Dependovirus/genetics/*immunology ; Genetic Vectors/*administration & dosage/*immunology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; *Transduction, Genetic ; },
abstract = {AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV's low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model. iDC internalized AAV vectors of various serotypes, but even the most efficient serotype failed to transduce iDC above background. Since AAV vectors reached the cell nucleus, we hypothesized that AAV's intracellular processing occurs suboptimal. On this basis, we screened an AAV peptide display library for capsid variants more suitable for DC transduction and identified the I/VSS family which transduced DC with efficiencies of up to 38%. This property correlated with an improved vector uncoating. To determine the consequence of this novel feature for AAV's in vivo performance, we engineered one of the lead candidates to express a cytoplasmic form of ovalbumin, a highly immunogenic model antigen, and assayed transduction efficiency as well as immunogenicity. The capsid variant clearly outperformed the parental serotype in muscle transduction and in inducing antigen-specific humoral and T cell responses as well as anti-capsid CD8+ T cells. Hence, vector uncoating represents a major barrier hampering AAV vector-mediated transduction of DC and impacts on its use as vaccine platform.},
}

Animals
CD8-Positive T-Lymphocytes/immunology/virology
Capsid/*immunology
Capsid Proteins/*immunology
Dendritic Cells/*immunology/virology
Dependovirus/genetics/*immunology
Genetic Vectors/*administration & dosage/*immunology
Humans
Male
Mice
Mice, Inbred C57BL
*Transduction, Genetic

@article {pmid32947148,
year = {2020},
author = {Zhang, J and Lu, CY and Chen, CH and Chen, HM and Wu, SY},
title = {Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis.},
journal = {Breast (Edinburgh, Scotland)},
volume = {54},
number = {},
pages = {70-78},
doi = {10.1016/j.breast.2020.08.017},
pmid = {32947148},
issn = {1532-3080},
abstract = {PURPOSE: To use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).

PATIENTS AND METHODS: We enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.

RESULTS: After multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52-0.81, P < 0.0001) and 0.58 (0.47-0.71, P < 0.0001) in postchemotherapy pathologic tumor stages T2-4 (ypT3-4) and postchemotherapy pathologic nodal stages N2-3 (ypN2-3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38-0.69, P < 0.0001), 0.60 (0.40-0.88, P = 0.0096), and 0.64 (0.48-0.86, P = 0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0-4, ypN0-3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.

CONCLUSION: For patients with breast cancer ypT3-4, ypN2-3, or pathologic stages IIIA-IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.},
}

@article {pmid31929443,
year = {2020},
author = {Eckert, L and Mattia, L and Patel, S and Okumura, R and Reynolds, P and Stuiver, I},
title = {Reducing the Risk of Indwelling Catheter-Associated Urinary Tract Infection in Female Patients by Implementing an Alternative Female External Urinary Collection Device: A Quality Improvement Project.},
journal = {Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society},
volume = {47},
number = {1},
pages = {50-53},
doi = {10.1097/WON.0000000000000601},
pmid = {31929443},
issn = {1528-3976},
mesh = {Adult ; California ; Catheter-Related Infections/prevention & control ; Catheters, Indwelling/*adverse effects/microbiology ; Female ; Humans ; Quality Improvement ; Urinary Tract Infections/*prevention & control ; Urine Specimen Collection/methods/*standards/statistics & numerical data ; },
abstract = {PURPOSE: The purpose of this quality improvement project was to reduce catheter-associated urinary tract infection (CAUTI) risk for female patients by implementing a female external urinary collection (FEUC) device with suction as an alternative to indwelling catheter (IDC).

PARTICIPANTS AND SETTING: Participants were female patients admitted to our 386-bed community hospital in Southern California and who required urinary management.

APPROACH: We implemented a comprehensive CAUTI prevention program in 2014 that was in place for 1.5 years before this project was started. The CAUTI prevention program was based on the US Center for Disease Control and Prevention's CAUTI prevention recommendations. To supplement our CAUTI prevention efforts in our female patients, we implemented the FEUC device in our intensive care, telemetry, medical-surgical, orthopedic, and acute rehabilitations inpatient care units. Indwelling catheter use and CAUTI cases were identified by our Infection Prevention department.

OUTCOMES: Prior to introduction of the FEUC device, in 2015, the baseline female IDC utilization rate was 31.7% (7181 IDC device-days/22,656 patient-days) and the female CAUTI rate was 1.11 (8 cases/7181 IDC device-days) per 1000 days. Following introduction of the device, both rates declined. In 2016, the IDC utilization rate was 29.7% (P = .000) and the CAUTI rate was 0% (P =.005). We continued to observe a reduction in 2017 IDC utilization rates of 26% (P = .000); the 2017 CAUTI rate of 0.90 was not significantly different to our prior year rate (P = .726).

IMPLICATIONS FOR PRACTICE: We found that the introduction of the FEUC device reduced the risk for CAUTI. We will continue to prioritize the use of external devices for urinary management to help reduce the risk of our patients developing CAUTI.},
}

Adult
California
Catheter-Related Infections/prevention & control
Catheters, Indwelling/*adverse effects/microbiology
Female
Humans
Quality Improvement
Urinary Tract Infections/*prevention & control
Urine Specimen Collection/methods/*standards/statistics & numerical data

@article {pmid32103749,
year = {2020},
author = {Tewari, SG and Swift, RP and Reifman, J and Prigge, ST and Wallqvist, A},
title = {Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite.},
journal = {Malaria journal},
volume = {19},
number = {1},
pages = {94},
pmid = {32103749},
issn = {1475-2875},
support = {R01 AI125534/AI/NIAID NIH HHS/United States ; R01 AI065853/NH/NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; W81XWH-15-C-0061//U.S. Army Medical Research and Development Command/ ; },
mesh = {Erythrocytes/*metabolism/parasitology ; Malaria, Falciparum/*metabolism/parasitology ; Parasitemia/*metabolism/parasitology ; Plasmodium falciparum/*growth & development ; },
abstract = {BACKGROUND: Human blood cells (erythrocytes) serve as hosts for the malaria parasite Plasmodium falciparum during its 48-h intraerythrocytic developmental cycle (IDC). Established in vitro protocols allow for the study of host-parasite interactions during this phase and, in particular, high-resolution metabolomics can provide a window into host-parasite interactions that support parasite development.

METHODS: Uninfected and parasite-infected erythrocyte cultures were maintained at 2% haematocrit for the duration of the IDC, while parasitaemia was maintained at 7% in the infected cultures. The parasite-infected cultures were synchronized to obtain stage-dependent information of parasite development during the IDC. Samples were collected in quadruplicate at six time points from the uninfected and parasite-infected cultures and global metabolomics was used to analyse cell fractions of these cultures.

RESULTS: In uninfected and parasite-infected cultures during the IDC, 501 intracellular metabolites, including 223 lipid metabolites, were successfully quantified. Of these, 19 distinct metabolites were present only in the parasite-infected culture, 10 of which increased to twofold in abundance during the IDC. This work quantified approximately five times the metabolites measured in previous studies of similar research scope, which allowed for more detailed analyses. Enrichment in lipid metabolism pathways exhibited a time-dependent association with different classes of lipids during the IDC. Specifically, enrichment occurred in sphingolipids at the earlier stages, and subsequently in lysophospholipid and phospholipid metabolites at the intermediate and end stages of the IDC, respectively. In addition, there was an accumulation of 18-, 20-, and 22-carbon polyunsaturated fatty acids, which produce eicosanoids and promote gametocytogenesis in infected erythrocyte cultures.

CONCLUSIONS: The current study revealed a number of heretofore unidentified metabolic components of the host-parasite system, which the parasite may exploit in a time-dependent manner to grow over the course of its development in the blood stage. Notably, the analyses identified components, such as precursors of immunomodulatory molecules, stage-dependent lipid dynamics, and metabolites, unique to parasite-infected cultures. These conclusions are reinforced by the metabolic alterations that were characterized during the IDC, which were in close agreement with those known from previous studies of blood-stage infection.},
}

Erythrocytes/*metabolism/parasitology
Malaria, Falciparum/*metabolism/parasitology
Parasitemia/*metabolism/parasitology
Plasmodium falciparum/*growth & development

@article {pmid32846803,
year = {2020},
author = {Li, G and Yao, J and Wu, T and Chen, Y and Wang, Z and Wang, Y and Wang, F and Zhong, R and Yang, S},
title = {Triple metachronous primary cancer of uterus, colon, and breast cancer: A case report and review of the literature.},
journal = {Medicine},
volume = {99},
number = {34},
pages = {e21764},
pmid = {32846803},
issn = {1536-5964},
mesh = {Aged ; Breast Neoplasms/*complications/pathology/therapy ; Colonic Neoplasms/*complications ; Female ; Humans ; Mammography ; Mastectomy ; Sentinel Lymph Node Biopsy ; Uterine Neoplasms/*complications ; },
abstract = {RATIONALE: Triple or more primary malignancies are rare, with only 23 previous cases including breast cancer reported in the English language studies between January 1990 and December 2019.

PATIENT CONCERNS: The patient was a 67-year-old woman with a mass in her right breast. She had a previous history of uterine and colon cancer. Both ultrasonography and mammography revealed a Breast Imaging Reporting and Data System (BI-RADS) category 3 breast lesion, in which proliferative nodules are more likely. Given her previous history of 2 malignancies, her doctors strongly recommended a biopsy.

DIAGNOSIS AND INTERVENTIONS: The biopsy pathology suggested intraductal breast cancer. Mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological diagnosis was invasive ductal carcinoma, grade II, stage I. The sample was positive for estrogen receptor and progesterone receptor and negative for cerbB-2. No radiotherapy or chemotherapy was administered except for endocrine therapy. A follow-up at 19 months showed no breast recurrence or distant metastases.

OUTCOMES: No recurrence or distant metastasis occurred within the 19-month, 11-year, and 20-year follow-ups for breast, colon, and uterine cancers, respectively.

LESSONS: To our knowledge, this is the first review of triple or more primary malignancies including breast cancer. These malignancies occur predominantly in older female patients. The most prevalent tumors of triple or more primary malignancies including breast cancer occur in the colon, uterus, and lung. A favorable prognosis is associated with early-stage malignancies.},
}

Aged
Breast Neoplasms/*complications/pathology/therapy
Colonic Neoplasms/*complications
Female
Humans
Mammography
Mastectomy
Sentinel Lymph Node Biopsy
Uterine Neoplasms/*complications

@article {pmid31927471,
year = {2020},
author = {Mema, E and Schnabel, F and Chun, J and Kaplowitz, E and Price, A and Goodgal, J and Moy, L},
title = {The relationship of breast density in mammography and magnetic resonance imaging in women with triple negative breast cancer.},
journal = {European journal of radiology},
volume = {124},
number = {},
pages = {108813},
doi = {10.1016/j.ejrad.2020.108813},
pmid = {31927471},
issn = {1872-7727},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Breast Density/*physiology ; Cohort Studies ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Mammography/*methods ; Middle Aged ; Retrospective Studies ; Risk Factors ; Triple Negative Breast Neoplasms/*diagnostic imaging ; Young Adult ; },
abstract = {PURPOSE: To evaluate the relationship between mammographic density, background parenchymal enhancement and fibroglandular tissue on MRI in women with triple negative breast cancer (TNBC) compared to women with non-triple negative breast cancer (non-TNBC).

METHODS: The institutional Breast Cancer Database was queried to identify the clinicopathologic and imaging characteristics among women who underwent mammography and breast MRI between 2010-2018. Statistical analyses included Pearson's Chi Square, Wilcoxon Rank-Sum and logistic regression.

RESULTS: Of 2995 women, 225 (7.5 %) had TNBC with a median age of 60 years (23-96) and median follow-up of 5.69 years. Compared to women with non-TNBC, TNBC was associated with African-American race 36/225 (16 %), BRCA1,2 positivity 34/225 (15.1 %), previous history of breast cancer 35/225 (15.6 %), presenting on breast exam 126/225 (56 %) or MRI 13/225 (5.8 %), palpability 133/225 (59.1 %), more invasive ductal carcinoma (IDC) 208/225 (92.4 %), higher stage (stage III) 37/225 (16.5 %), higher grade (grade 3) 186/225 (82.7 %) (all p < 0.001), lower mammographic breast density (MBD) 18/225 (8 %) (p = 0.04), lower fibroglandular tissue (FGT) 17/225 (7.6 %) (p = 0.01), and lower background parenchymal enhancement (BPE) 89/225 (39.8 %) (p = 0.02). Nine of 225 (4 %) women with TNBC experienced recurrence with no significant association with MBD, FGT, or BPE. There was no significant difference in median age of our TNBC and non-TNBC cohorts.

CONCLUSIONS: The higher proportion of women with lower MBD, FGT and BPE in women with TNBC suggests that MBD, amount of FGT and degree of BPE may be associated with breast cancer risk in women with TNBC.},
}

Adult
Aged
Aged, 80 and over
Breast/diagnostic imaging
Breast Density/*physiology
Cohort Studies
Female
Humans
Magnetic Resonance Imaging/*methods
Mammography/*methods
Middle Aged
Retrospective Studies
Risk Factors
Triple Negative Breast Neoplasms/*diagnostic imaging
Young Adult

@article {pmid31932496,
year = {2020},
author = {Jelacic, TM and Ribot, WJ and Chua, J and Boyer, AE and Woolfitt, AR and Barr, JR and Friedlander, AM},
title = {Human Innate Immune Cells Respond Differentially to Poly-γ-Glutamic Acid Polymers from Bacillus anthracis and Nonpathogenic Bacillus Species.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {204},
number = {5},
pages = {1263-1273},
doi = {10.4049/jimmunol.1901066},
pmid = {31932496},
issn = {1550-6606},
mesh = {Bacillus anthracis/*immunology ; Bacillus licheniformis/*immunology ; Bacillus subtilis/*immunology ; Cytokines/immunology ; Dendritic Cells/*immunology ; Female ; Humans ; *Immunity, Innate ; Macrophages/*immunology ; Male ; Monocytes/*immunology ; Polyglutamic Acid/*immunology ; },
abstract = {The poly-γ-glutamic acid (PGA) capsule produced by Bacillus anthracis is composed entirely of d-isomer glutamic acid, whereas nonpathogenic Bacillus species produce mixed d-, l-isomer PGAs. To determine if B. anthracis PGA confers a pathogenic advantage over other PGAs, we compared the responses of human innate immune cells to B. anthracis PGA and PGAs from nonpathogenic B. subtilis subsp. chungkookjang and B. licheniformis Monocytes and immature dendritic cells (iDCs) responded differentially to the PGAs, with B. anthracis PGA being least stimulatory and B. licheniformis PGA most stimulatory. All three elicited IL-8 and IL-6 from monocytes, but B. subtilis PGA also elicited IL-10 and TNF-α, whereas B. licheniformis PGA elicited all those plus IL-1β. Similarly, all three PGAs elicited IL-8 from iDCs, but B. subtilis PGA also elicited IL-6, and B. licheniformis PGA elicited those plus IL-12p70, IL-10, IL-1β, and TNF-α. Only B. licheniformis PGA induced dendritic cell maturation. TLR assays also yielded differential results. B. subtilis PGA and B. licheniformis PGA both elicited more TLR2 signal than B. anthracis PGA, but only responses to B. subtilis PGA were affected by a TLR6 neutralizing Ab. B. licheniformis PGA elicited more TLR4 signal than B. anthracis PGA, whereas B. subtilis PGA elicited none. B. anthracis PGA persisted longer in high m.w. form in monocyte and iDC cultures than the other PGAs. Reducing the m.w. of B. anthracis PGA reduced monocytes' cytokine responses. We conclude that B. anthracis PGA is recognized less effectively by innate immune cells than PGAs from nonpathogenic Bacillus species, resulting in failure to induce a robust host response, which may contribute to anthrax pathogenesis.},
}

Bacillus anthracis/*immunology
Bacillus licheniformis/*immunology
Bacillus subtilis/*immunology
Cytokines/immunology
Dendritic Cells/*immunology
Female
Humans
*Immunity, Innate
Macrophages/*immunology
Male
Monocytes/*immunology
Polyglutamic Acid/*immunology

@article {pmid31291711,
year = {2020},
author = {Xu, Q and Shao, Y and Zhang, J and Zhang, H and Zhao, Y and Liu, X and Guo, Z and Chong, W and Gu, F and Ma, Y},
title = {Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response.},
journal = {Cancer research and treatment : official journal of Korean Cancer Association},
volume = {52},
number = {1},
pages = {218-245},
pmid = {31291711},
issn = {2005-9256},
support = {81572851//National Scientific Foundation of China/ ; 81672636//National Scientific Foundation of China/ ; },
mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*drug therapy/*etiology/mortality ; Carrier Proteins/*genetics ; Cell Transformation, Neoplastic/*genetics ; *Disease Susceptibility ; Female ; Gene Expression ; Humans ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Proteins/*genetics ; Prognosis ; Recurrence ; Treatment Outcome ; Tumor Burden ; },
abstract = {PURPOSE: Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression.

Materials and Methods: AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3's correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3's impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected.

RESULTS: AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines.

CONCLUSION: AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.},
}

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
Biomarkers, Tumor
Breast Neoplasms/diagnosis/*drug therapy/*etiology/mortality
Carrier Proteins/*genetics
Cell Transformation, Neoplastic/*genetics
*Disease Susceptibility
Female
Gene Expression
Humans
Middle Aged
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Proteins/*genetics
Prognosis
Recurrence
Treatment Outcome
Tumor Burden

@article {pmid32876204,
year = {2020},
author = {Salim, TR and Andrade, TM and Klein, CH and Oliveira, GMM},
title = {Inequalities in Mortality Rates from Malformations of Circulatory System Between Brazilian Macroregions in Individuals Younger Than 20 Years.},
journal = {Arquivos brasileiros de cardiologia},
volume = {},
number = {},
pages = {},
doi = {10.36660/abc.20190351},
pmid = {32876204},
issn = {1678-4170},
abstract = {Background Deaths from malformations of the circulatory system (MCS) have a major impact on mortality reduction. given that most cases are avoidable with correct diagnosis and treatment. Objectives To describe the distribution of mortality from MCS by sex. age. and macroregion in Brazil. in individuals under the age of 20. between 2000 and 2015. Methods A descriptive study of mortality rates and proportional mortality (PM) from MCS. other congenital malformations (OCM). circulatory system disease (CSD). ill-defined causes (IDC). and external causes (EC) in Brazil. Results There were 1.367.355 deaths from all causes in individuals younger than 20. 55.0% under 1 year of age. A total of 144.057 deaths were caused by congenital malformations. 39% of them by MCS. In both sexes. the annual mortality from MCS was 5.3/100.000. PM from MCS was 4.2%. CSD 2.2%. IDC 6.2% and EC 24.9%. Unspecified MCS showed the highest PM rates in both sexes and age groups. especially in the north and northeast regions (60%). Deaths from malformations occurred 5.7 times more frequently during the first year of life than in other ages (MCS: 5.0; OCM: 6.4). Conclusions MCS was the leading cause of death among all malformations. being twice as important as CSD. mainly under 1 year of age. The frequency of misdiagnosis of MCS as cause of death was high in all ages and both sexes. especially in the north and northeast regions. These findings highlight the need for the development of public health strategies focused on correct diagnosis and early treatment of congenital cardiopathies. leading to a reduction in mortality. (Arq Bras Cardiol. 2020; [online].ahead print. PP.0-0).},
}

@article {pmid31765735,
year = {2020},
author = {Morimoto, M and Horikoshi, Y and Nakaso, K and Kurashiki, T and Kitagawa, Y and Hanaki, T and Sakamoto, T and Honjo, S and Umekita, Y and Fujiwara, Y and Matsura, T},
title = {Oncogenic role of TYRO3 receptor tyrosine kinase in the progression of pancreatic cancer.},
journal = {Cancer letters},
volume = {470},
number = {},
pages = {149-160},
doi = {10.1016/j.canlet.2019.11.028},
pmid = {31765735},
issn = {1872-7980},
mesh = {Aged ; Animals ; Carcinogenesis ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Female ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; MAP Kinase Signaling System ; Male ; Mice ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Pancreas/pathology ; Pancreatic Neoplasms/mortality/*pathology ; Phosphorylation ; Prognosis ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/*metabolism ; Xenograft Model Antitumor Assays ; },
abstract = {The expression and functions of TYRO3, a member of the TAM receptor tyrosine kinase family, in pancreatic cancer (PC) have not been specifically elucidated. In this study, we confirmed TYRO3 expression in five human PC cell lines (PANC-1, MIA PaCa-2, BxPC-3, AsPC-1, and PK-9) using Western blotting. TYRO3 silencing and overexpression studies have revealed that TYRO3 promotes cell proliferation and invasion in PC via phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK). Using a mouse xenograft model, we showed that tumor growth was significantly suppressed in mice subcutaneously inoculated with TYRO3-knockdown PC cells compared with mice inoculated with control PC cells. Furthermore, TYRO3 expression was examined in PC tissues obtained from 106 patients who underwent pancreatic resection for invasive ductal carcinoma through immunohistochemical staining. TYRO3-positive patients had poor prognoses for overall survival and disease-specific survival compared with TYRO3-negative patients. Multivariate analysis revealed that TYRO3 expression is an independent prognostic factor for overall survival. Our study demonstrates the critical role of TYRO3 in PC progression through Akt and ERK activation and suggests TYRO3 as a novel promising target for therapeutic strategies against PC.},
}

Aged
Animals
Carcinogenesis
Cell Line, Tumor
Cell Proliferation
Disease Progression
Female
Gene Knockdown Techniques
Humans
Kaplan-Meier Estimate
MAP Kinase Signaling System
Male
Mice
Middle Aged
Neoplasm Invasiveness/pathology
Neoplasm Staging
Pancreas/pathology
Pancreatic Neoplasms/mortality/*pathology
Phosphorylation
Prognosis
Proto-Oncogene Proteins c-akt/metabolism
RNA, Small Interfering/metabolism
Receptor Protein-Tyrosine Kinases/genetics/*metabolism
Xenograft Model Antitumor Assays

@article {pmid32856854,
year = {2020},
author = {Chowdhury, SS and Khatun, M and Khan, TH and Laila, AB},
title = {Mutation in Exon2 of BRCA1 Gene in Adult Bengali Bangladeshi Female Patients with Breast Cancer: An Experience from Two Tertiary-Care Hospitals.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {21},
number = {8},
pages = {2265-2270},
doi = {10.31557/APJCP.2020.21.8.2265},
pmid = {32856854},
issn = {2476-762X},
abstract = {BACKGROUND: The occurrence rate of BRCA1 mutations is found to be high in South Asian countries where early onset of breast cancer is common. In Bangladesh, noticeable percentage of patients experience breast cancer in their reproductive ages. The objective of this study was to identify any mutation in exon2 of the BRCA1 gene in adult Bengali Bangladeshi female patients with breast cancer.

METHODS: In this cross-sectional descriptive study, the genomic DNA was extracted from the blood of adult fifty Bengali Bangladeshi female breast cancer patients. The whole region of exon2 of the BRCA1 gene was amplified and the amplified DNA products were sequenced using Sanger sequencing. The raw chromatogram data were analyzed using Chromas software, and analyzed sequences were compared with the NCBI RefSeq database by BLAST search. The resultant amino acid change was detected by MEGA X software.

RESULTS: We found the mean age at diagnosis 44.66 years, whereas 96% of patients were married, 90% were multiparous and 86% breastfed their children. All patients had unilateral breast cancer and among them 94% had invasive ductal carcinoma. Only 24.5% of the patients had associated omorbidity. The family history of breast cancer or other BRCA-associated cancer was positive only for 4% of patients. A total of five mutations were identified all of which caused by substitutions. Among them three were nonsynonymous and two were synonymous. Only 2.5% of the patients, within the age group of 18-50 years, were found to have mutations in their blood, whereas 26.66% of the patients above 50 years found to have mutations in this study.

CONCLUSIONS: Among this small sample size, we found five mutations in exon2 of the BRCA1 gene and this indicates the necessity to find out the mutation spectra of the BRCA1 gene in the Bangladeshi population.},
}

@article {pmid32544183,
year = {2020},
author = {Moon, HR and Ospina-Muñoz, N and Noe-Kim, V and Yang, Y and Elzey, BD and Konieczny, SF and Han, B},
title = {Subtype-specific characterization of breast cancer invasion using a microfluidic tumor platform.},
journal = {PloS one},
volume = {15},
number = {6},
pages = {e0234012},
pmid = {32544183},
issn = {1932-6203},
support = {HHSN261201400021C/CA/NCI NIH HHS/United States ; UL1 TR000006/TR/NCATS NIH HHS/United States ; P30 CA023168/CA/NCI NIH HHS/United States ; },
mesh = {CD24 Antigen/metabolism ; Carcinoma, Ductal, Breast/classification/genetics/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; Humans ; Microfluidics/methods ; Neoplasm Invasiveness ; Neoplasm Staging ; Triple Negative Breast Neoplasms/classification/genetics/*pathology ; *Tumor Microenvironment ; },
abstract = {Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.},
}

CD24 Antigen/metabolism
Carcinoma, Ductal, Breast/classification/genetics/*pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Humans
Microfluidics/methods
Neoplasm Invasiveness
Neoplasm Staging
Triple Negative Breast Neoplasms/classification/genetics/*pathology
*Tumor Microenvironment

@article {pmid32488076,
year = {2020},
author = {Subudhi, AK and O'Donnell, AJ and Ramaprasad, A and Abkallo, HM and Kaushik, A and Ansari, HR and Abdel-Haleem, AM and Ben Rached, F and Kaneko, O and Culleton, R and Reece, SE and Pain, A},
title = {Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms.},
journal = {Nature communications},
volume = {11},
number = {1},
pages = {2763},
doi = {10.1038/s41467-020-16593-y},
pmid = {32488076},
issn = {2041-1723},
support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 204511/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Animals ; Caenorhabditis elegans Proteins ; Circadian Rhythm/*physiology ; Disease Models, Animal ; Erythropoiesis/*physiology ; Female ; Gene Expression ; Host-Parasite Interactions/genetics/*physiology ; Humans ; Malaria/*metabolism/parasitology ; Mice ; Mice, Knockout ; Plasmodium chabaudi/genetics/growth & development ; Plasmodium falciparum/genetics/growth & development ; Protozoan Proteins/genetics/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Rodentia ; Secologanin Tryptamine Alkaloids/*metabolism ; Transcriptome ; },
abstract = {Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.},
}

Animals
Caenorhabditis elegans Proteins
Circadian Rhythm/*physiology
Disease Models, Animal
Erythropoiesis/*physiology
Female
Gene Expression
Host-Parasite Interactions/genetics/*physiology
Humans
Malaria/*metabolism/parasitology
Mice
Mice, Knockout
Plasmodium chabaudi/genetics/growth & development
Plasmodium falciparum/genetics/growth & development
Protozoan Proteins/genetics/*metabolism
Receptors, G-Protein-Coupled/genetics/*metabolism
Rodentia
Secologanin Tryptamine Alkaloids/*metabolism
Transcriptome

@article {pmid31217350,
year = {2019},
author = {Lodd, E and Wiggenhauser, LM and Morgenstern, J and Fleming, TH and Poschet, G and Büttner, M and Tabler, CT and Wohlfart, DP and Nawroth, PP and Kroll, J},
title = {The combination of loss of glyoxalase1 and obesity results in hyperglycemia.},
journal = {JCI insight},
volume = {4},
number = {12},
pages = {},
pmid = {31217350},
issn = {2379-3708},
mesh = {Animals ; CRISPR-Cas Systems ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2/genetics ; Diet ; Disease Models, Animal ; Gene Knockout Techniques ; Genetic Predisposition to Disease ; Glucose/metabolism ; Hyperglycemia/*etiology/genetics ; Insulin Resistance ; Lactoylglutathione Lyase/genetics/*physiology ; Liver/metabolism ; Male ; Obesity/*complications ; Pyruvaldehyde/metabolism ; Retina/pathology ; Zebrafish/growth & development ; },
abstract = {The increased formation of methylglyoxal (MG) under hyperglycemia is associated with the development of microvascular complications in patients with diabetes mellitus; however, the effects of elevated MG levels in vivo are poorly understood. In zebrafish, a transient knockdown of glyoxalase 1, the main MG detoxifying system, led to the elevation of endogenous MG levels and blood vessel alterations. To evaluate effects of a permanent knockout of glyoxalase 1 in vivo, glo1-/- zebrafish mutants were generated using CRISPR/Cas9. In addition, a diet-induced-obesity zebrafish model was used to analyze glo1-/- zebrafish under high nutrient intake. Glo1-/- zebrafish survived until adulthood without growth deficit and showed increased tissue MG concentrations. Impaired glucose tolerance developed in adult glo1-/- zebrafish and was indicated by increased postprandial blood glucose levels and postprandial S6 kinase activation. Challenged by an overfeeding period, fasting blood glucose levels in glo1-/- zebrafish were increased which translated into retinal blood vessel alterations. Thus, the data have identified a defective MG detoxification as a metabolic prerequisite and glyoxalase 1 alterations as a genetic susceptibility to the development of type 2 diabetes mellitus under high nutrition intake.},
}

Animals
CRISPR-Cas Systems
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 2/genetics
Diet
Disease Models, Animal
Gene Knockout Techniques
Genetic Predisposition to Disease
Glucose/metabolism
Hyperglycemia/*etiology/genetics
Insulin Resistance
Lactoylglutathione Lyase/genetics/*physiology
Liver/metabolism
Male
Obesity/*complications
Pyruvaldehyde/metabolism
Retina/pathology
Zebrafish/growth & development

@article {pmid31894281,
year = {2020},
author = {Zhao, C and Zheng, S and Yan, Z and Deng, Z and Wang, R and Zhang, B},
title = {CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2.},
journal = {Oncology reports},
volume = {43},
number = {2},
pages = {571-580},
doi = {10.3892/or.2019.7426},
pmid = {31894281},
issn = {1791-2431},
mesh = {Adult ; Aged ; Animals ; Annexin A2/*metabolism ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Ductal, Breast/metabolism/*pathology ; Cell Line, Tumor ; Chemokines, CC/*metabolism ; Disease Progression ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/metabolism/*pathology/*secondary ; MCF-7 Cells ; Mice ; Middle Aged ; Neoplasm Transplantation ; Tumor Burden ; },
abstract = {Chemokine (C‑C motif) ligand 18 (CCL18) is derived from breast tumor‑associated macrophages (TAMs), which are primarily a macrophage subpopulation with an M2 phenotype. CCL18 binds to its receptor, PYK2 N‑terminal domain interacting receptor 1 (Nir1), and promotes tumor progression and metastasis by inducing epithelial‑mesenchymal transition (EMT) via the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer cells. Recent research shows that Annexin A2 (AnxA2) plays a significant role in the invasion, metastasis, angiogenesis, proliferation, F‑actin polymerization and multidrug resistance to chemotherapy of breast cancer. The present study aimed to elucidate the molecular mechanisms by which CCL18 promotes breast cancer progression through AnxA2 which are not fully understood. Western blot analysis showed that the expression of AnxA2 was upregulated in highly invasive breast cancer cell lines and invasive ductal carcinoma. Furthermore, through chemotaxis, scratch, Matrigel invasion, and spontaneous metastasis assays, it was demonstrated that AnxA2 enhanced the invasion of breast cancer cells and the metastasis of human breast cancer cells to lungs of SCID mice with CCL18 stimulation. Cellular F‑actin measurement assay showed that reduction of AnxA2 suppressed CCL18‑induced F‑actin polymerization though phosphorylation of integrin β1 in breast cancer cells. Immunofluorescence and western blot analysis revealed that AnxA2 promoted CCL18‑induced EMT via the PI3K/Akt/GSK3β/Snail signaling pathway, and LY294002 inhibited the phosphorylation of AnxA2 in vitro. In brief, AnxA2, as a downstream molecule of Nir 1 binding to CCL18, promotes invasion and metastasis by EMT through the PI3K/Akt/GSK3β/Snail signaling pathway in breast cancer. This study suggests that AnxA2 is a potential anti‑invasion/metastasis target for therapeutic intervention in breast cancer.},
}

Adult
Aged
Animals
Annexin A2/*metabolism
Breast Neoplasms/metabolism/*pathology
Carcinoma, Ductal, Breast/metabolism/*pathology
Cell Line, Tumor
Chemokines, CC/*metabolism
Disease Progression
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms/metabolism/*pathology/*secondary
MCF-7 Cells
Mice
Middle Aged
Neoplasm Transplantation
Tumor Burden

@article {pmid30728399,
year = {2019},
author = {Kaur, P and Porras, TB and Ring, A and Carpten, JD and Lang, JE},
title = {Comparison of TCGA and GENIE genomic datasets for the detection of clinically actionable alterations in breast cancer.},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {1482},
pmid = {30728399},
issn = {2045-2322},
support = {P30 CA014089/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/*genetics/pathology ; Computer Simulation ; DNA Copy Number Variations/genetics ; Databases, Genetic/*standards/*trends ; Exome/genetics ; Female ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Mutation/genetics ; Precision Medicine/methods ; },
abstract = {Whole exome sequencing (WES), targeted gene panel sequencing and single nucleotide polymorphism (SNP) arrays are increasingly used for the identification of actionable alterations that are critical to cancer care. Here, we compared The Cancer Genome Atlas (TCGA) and the Genomics Evidence Neoplasia Information Exchange (GENIE) breast cancer genomic datasets (array and next generation sequencing (NGS) data) in detecting genomic alterations in clinically relevant genes. We performed an in silico analysis to determine the concordance in the frequencies of actionable mutations and copy number alterations/aberrations (CNAs) in the two most common breast cancer histologies, invasive lobular and invasive ductal carcinoma. We found that targeted sequencing identified a larger number of mutational hotspots and clinically significant amplifications that would have been missed by WES and SNP arrays in many actionable genes such as PIK3CA, EGFR, AKT3, FGFR1, ERBB2, ERBB3 and ESR1. The striking differences between the number of mutational hotspots and CNAs generated from these platforms highlight a number of factors that should be considered in the interpretation of array and NGS-based genomic data for precision medicine. Targeted panel sequencing was preferable to WES to define the full spectrum of somatic mutations present in a tumor.},
}

Breast Neoplasms/*genetics/pathology
Computer Simulation
DNA Copy Number Variations/genetics
Databases, Genetic/*standards/*trends
Exome/genetics
Female
Genomics/methods
High-Throughput Nucleotide Sequencing/methods
Humans
Mutation/genetics
Precision Medicine/methods

@article {pmid31937300,
year = {2020},
author = {Westwood, ML and O'Donnell, AJ and Schneider, P and Albery, GF and Prior, KF and Reece, SE},
title = {Testing possible causes of gametocyte reduction in temporally out-of-synch malaria infections.},
journal = {Malaria journal},
volume = {19},
number = {1},
pages = {17},
pmid = {31937300},
issn = {1475-2875},
support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; UF110155//Royal Society/ ; },
mesh = {Animals ; *Circadian Rhythm/immunology ; Erythrocytes/*parasitology ; Female ; Flow Cytometry ; Gametogenesis/physiology ; Linear Models ; Malaria/blood/immunology/*parasitology ; Male ; Merozoites/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Plasmodium chabaudi/genetics/growth & development/immunology/*physiology ; Random Allocation ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Tumor Necrosis Factor-alpha/*administration & dosage/blood/immunology ; },
abstract = {BACKGROUND: The intraerythrocytic development cycle (IDC) of the rodent malaria Plasmodium chabaudi is coordinated with host circadian rhythms. When this coordination is disrupted, parasites suffer a 50% reduction in both asexual stages and sexual stage gametocytes over the acute phase of infection. Reduced gametocyte density may not simply follow from a loss of asexuals because investment into gametocytes ("conversion rate") is a plastic trait; furthermore, the densities of both asexuals and gametocytes are highly dynamic during infection. Hence, the reasons for the reduction of gametocytes in infections that are out-of-synch with host circadian rhythms remain unclear. Here, two explanations are tested: first, whether out-of-synch parasites reduce their conversion rate to prioritize asexual replication via reproductive restraint; second, whether out-of-synch gametocytes experience elevated clearance by the host's circadian immune responses.

METHODS: First, conversion rate data were analysed from a previous experiment comparing infections of P. chabaudi that were in-synch or 12 h out-of-synch with host circadian rhythms. Second, three new experiments examined whether the inflammatory cytokine TNF varies in its gametocytocidal efficacy according to host time-of-day and gametocyte age.

RESULTS: There was no evidence that parasites reduce conversion or that their gametocytes become more vulnerable to TNF when out-of-synch with host circadian rhythms.

CONCLUSIONS: The factors causing the reduction of gametocytes in out-of-synch infections remain mysterious. Candidates for future investigation include alternative rhythmic factors involved in innate immune responses and the rhythmicity in essential resources required for gametocyte development. Explaining why it matters for gametocytes to be synchronized to host circadian rhythms might suggest novel approaches to blocking transmission.},
}

Animals
*Circadian Rhythm/immunology
Erythrocytes/*parasitology
Female
Flow Cytometry
Gametogenesis/physiology
Linear Models
Malaria/blood/immunology/*parasitology
Male
Merozoites/physiology
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Plasmodium chabaudi/genetics/growth & development/immunology/*physiology
Random Allocation
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Tumor Necrosis Factor-alpha/*administration & dosage/blood/immunology

@article {pmid30985953,
year = {2019},
author = {Erro, R and Picillo, M and Amboni, M and Savastano, R and Scannapieco, S and Cuoco, S and Santangelo, G and Vitale, C and Pellecchia, MT and Barone, P},
title = {Comparing postural instability and gait disorder and akinetic-rigid subtyping of Parkinson disease and their stability over time.},
journal = {European journal of neurology},
volume = {26},
number = {9},
pages = {1212-1218},
doi = {10.1111/ene.13968},
pmid = {30985953},
issn = {1468-1331},
mesh = {Aged ; Female ; Gait Disorders, Neurologic/etiology/*physiopathology ; Humans ; Hypokinesia/etiology/*physiopathology ; Longitudinal Studies ; Male ; Middle Aged ; Parkinson Disease/classification/complications/*physiopathology ; Postural Balance/*physiology ; Tremor/etiology/*physiopathology ; },
abstract = {BACKGROUND AND PURPOSE: Parkinson disease (PD) patients are classically classified according to two alternative motor subtyping methods: (i) tremor-dominant versus postural instability and gait disorder; (ii) tremor-dominant versus akinetic-rigid. The degree of overlap between the two classification systems at diagnosis of PD and their temporal stability, as well as the correspondence between the two systems, were examined over a follow-up period of 4 years.

METHODS: Newly diagnosed, untreated PD patients were classified as tremor-dominant versus postural instability and gait disorder and tremor-dominant versus akinetic-rigid at baseline and after 2 and 4 years.

RESULTS: There was a poor overlap between the two classification systems at any time point and baseline subtype status could not predict 4-year subtype membership. In fact, about half of our cohort shifted category during the first 2 years, regardless of the classification scheme adopted. A lower rate of shift was observed from 2- to 4-year follow-up.

CONCLUSIONS: The two classical motor subtyping methods of PD poorly overlap, which implies that a patient can be categorized as tremor-dominant in one classification system but not in the other. Moreover, their temporal instability undermines their prognostic value in the early stage of PD.},
}

Aged
Female
Gait Disorders, Neurologic/etiology/*physiopathology
Humans
Hypokinesia/etiology/*physiopathology
Longitudinal Studies
Male
Middle Aged
Parkinson Disease/classification/complications/*physiopathology
Postural Balance/*physiology
Tremor/etiology/*physiopathology

@article {pmid31004170,
year = {2019},
author = {Harbertson, J and Scott, PT and Lemus, H and Michael, NL and Hale, BR},
title = {Cross-Sectional Study of Sexual Behavior, Alcohol Use, and Mental Health Conditions Associated With Sexually Transmitted Infections Among Deploying Shipboard US Military Personnel.},
journal = {Military medicine},
volume = {184},
number = {11-12},
pages = {e693-e700},
doi = {10.1093/milmed/usz070},
pmid = {31004170},
issn = {1930-613X},
mesh = {Adult ; Alcohol Drinking/adverse effects/epidemiology/*psychology ; Cross-Sectional Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Mental Disorders/*diagnosis/epidemiology/psychology ; Middle Aged ; Military Personnel/psychology/*statistics & numerical data ; Risk Factors ; Risk-Taking ; Sexual Behavior/*psychology ; Sexually Transmitted Diseases/*diagnosis/epidemiology/psychology ; Ships/statistics & numerical data ; United States/epidemiology ; },
abstract = {INTRODUCTION: Limited comprehensive data exist on risk behavior associated with sexually transmitted infections (STI) among ship-assigned US military personnel during the predeployment time period (PDT). This study examined whether sexual risk behaviors, alcohol use, involuntary drug consumption (IDC), posttraumatic stress disorder (PTSD), and depression during the 12 months prior to deployment were associated with provider-diagnosed STIs in this population.

MATERIALS AND METHODS: Using cross-sectional data collected during 2012-2014 among sexually active personnel, multivariable regression assessed factors associated with STIs among all men (n = 1,831). Stratified analyses were conducted among men who have sex with women (MSW, n = 1,530), men who have sex with men or men and women (MSM, n = 83), and excluded those not reporting sexual partner gender (n = 218).

RESULTS: Among MSW, transactional sex (AOR 3.8, 95% CI 1.5-9.4) meeting sexual partners at work (AOR 4.3, 95% CI 2.0-9.2), IDC (AOR 6.6, 95% CI 3.0-14.5), and incomplete mental health assessments (AOR 4.4, 95% CI 1.6-12.0) were significantly associated with STIs after adjustment. Among all men, those who identified as MSM (AOR 4.6, 95% CI 1.9-11.2) and drug screen positive (AOR 3.3, 95% CI 1.3-8.6) were significantly more likely to report an STI.

CONCLUSIONS: Previously unreported factors significantly associated with STIs at the PDT among MSW in the adjusted analysis were meeting sexual partners at work and IDC. IDC during the PDT warrants further exploration. These results can inform tailored STI reduction interventions among shipboard personnel and similarly aged civilians undergoing similar transition/travel experiences.},
}

Adult
Alcohol Drinking/adverse effects/epidemiology/*psychology
Cross-Sectional Studies
Female
Humans
Longitudinal Studies
Male
Mental Disorders/*diagnosis/epidemiology/psychology
Middle Aged
Military Personnel/psychology/*statistics & numerical data
Risk Factors
Risk-Taking
Sexual Behavior/*psychology
Sexually Transmitted Diseases/*diagnosis/epidemiology/psychology
Ships/statistics & numerical data
United States/epidemiology

@article {pmid31929965,
year = {2019},
author = {Lin, L and Wang, X and Tang, C and Liang, J},
title = {Clinical Characteristics and Prognosis of Gastrointestinal Metastases in Solid Tumor Patients: A Retrospective Study and Review of Literatures.},
journal = {Analytical cellular pathology (Amsterdam)},
volume = {2019},
number = {},
pages = {4508756},
pmid = {31929965},
issn = {2210-7185},
mesh = {Adenocarcinoma/mortality/pathology/*secondary ; Adult ; Aged ; Breast Neoplasms/mortality/*pathology ; Carcinoma, Ductal/mortality/pathology/*secondary ; Female ; Gastrointestinal Neoplasms/mortality/*secondary ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*pathology ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms/mortality/*pathology ; },
abstract = {Background: According to the literature and our experience, patients with gastrointestinal metastases are relatively rare. Numerous case reports and literature reviews have been reported. We present one of the larger case series of gastrointestinal metastases.

Objectives: To explore the clinical characteristics and prognosis of patients with gastrointestinal tract metastases, which are rare metastatic sites.

Methods: Patients with gastrointestinal metastases in the setting of stage IV primary carcinomas treated at Beijing Ditan Hospital and Peking University International Hospital from November 1992 to August 2017 were included in this study. The diagnosis of gastrointestinal tract metastases was based on histopathology.

Results: 30 patients (median age 56 years, 56.7% female) were included. The most common primary carcinomas associated with gastrointestinal metastases were breast (11 patients, 36.7%), stomach (9 patients, 30.0%), and lung (4 patients, 13.3%) cancer. The major pathological types were adenocarcinoma (16 patients, 53.3%) and ductal carcinoma (9 patients, 30.0%). Ten patients (33.3%) underwent local gastrointestinal treatment, and 20 patients (66.7%) underwent nonlocal treatment (involving chemotherapy alone or best supportive care). For breast cancer patients and gastric cancer patients who underwent local therapy, a significant survival advantage was observed (p = 0.001 and p = 0.012, respectively). The presence of other common metastases was identified as an independent poor prognostic factor through multivariate analysis with a HR (hazard ratio) of survival of 0.182 (95% confidence interval (CI) 0.11-0.523, p = 0.031).

Conclusion: Gastrointestinal metastases are most frequently from breast invasive ductal carcinoma. The presentation of other common metastases with gastrointestinal metastasis indicates poor prognosis, and selected patients may benefit from surgical intervention.},
}

Adenocarcinoma/mortality/pathology/*secondary
Adult
Aged
Breast Neoplasms/mortality/*pathology
Carcinoma, Ductal/mortality/pathology/*secondary
Female
Gastrointestinal Neoplasms/mortality/*secondary
Humans
Kaplan-Meier Estimate
Lung Neoplasms/mortality/*pathology
Male
Middle Aged
Prognosis
Proportional Hazards Models
Retrospective Studies
Stomach Neoplasms/mortality/*pathology

@article {pmid31467444,
year = {2020},
author = {Sarhan, MS and Mourad, EF and Nemr, RA and Abdelfadeel, MR and Daanaa, HA and Youssef, HH and Goda, HA and Hamza, MA and Fayez, M and Eichler-Löbermann, B and Ruppel, S and Hegazi, NA},
title = {An inoculum-dependent culturing strategy (IDC) for the cultivation of environmental microbiomes and the isolation of novel endophytic Actinobacteria.},
journal = {The Journal of antibiotics},
volume = {73},
number = {1},
pages = {66-71},
doi = {10.1038/s41429-019-0226-4},
pmid = {31467444},
issn = {1881-1469},
mesh = {Actinobacteria/*chemistry ; Bacteriological Techniques ; Colony Count, Microbial ; Culture Media ; Endophytes/*chemistry ; *Microbiota ; Plant Roots/microbiology ; Plant Shoots/microbiology ; Plants/microbiology ; },
abstract = {The recent introduction of plant-only-based culture media enabled cultivation of not-yet-cultured bacteria that exceed 90% of the plant microbiota communities. Here, we further prove the competence and challenge of such culture media, and further introduce "the inoculum-dependent culturing strategy, IDC". The strategy depends on direct inoculating plant serial dilutions onto plain water agar plates, allowing bacteria to grow only on the expense of natural nutrients contained in the administered inoculum. Developed colonies are successively transferred/subcultured onto plant-only-based culture media, which contains natural nutrients very much alike to those found in the prepared plant inocula. Because of its simplicity, the method is recommended as a powerful tool in screening programs that require microbial isolation from a large number of diverse plants. Here, the method comfortably and successfully recovered several isolates of endophytic Actinobacteria represented by the six genera of Curtobacterium spp., Plantibacter spp., Agreia spp., Herbiconiux spp., Rhodococcus spp., and Nocardioides spp. Furthermore, two of the isolates are most likely novel species belonging to Agreia spp. and Herbiconiux spp.},
}

Actinobacteria/*chemistry
Bacteriological Techniques
Colony Count, Microbial
Culture Media
Endophytes/*chemistry
*Microbiota
Plant Roots/microbiology
Plant Shoots/microbiology
Plants/microbiology

@article {pmid31134761,
year = {2019},
author = {Chen, S and Chen, H and Yi, Y and Jiang, X and Lei, H and Luo, X and Chen, Y and Liu, S and Yuan, D and Jia, X and Li, J},
title = {Comparative study of breast cancer with or without concomitant Paget disease: An analysis of the SEER database.},
journal = {Cancer medicine},
volume = {8},
number = {8},
pages = {4043-4054},
pmid = {31134761},
issn = {2045-7634},
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Breast Neoplasms/*epidemiology/etiology/mortality/pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Paget's Disease, Mammary/*epidemiology/etiology/mortality/pathology ; Population Surveillance ; Prognosis ; SEER Program ; },
abstract = {BACKGROUND: Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone.

METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, 2000-2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD-IDC) and 1489 women who had PD with ductal carcinoma in situ (PD-DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD.

RESULTS: PD-IDC and PD-DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P = 0.182 in PD-IDC and P = 0.371 in PD-DCIS), HER2 status (P = 0.788 in PD-IDC and P = 0.643 in PD-DCIS), and combined molecular subtype (P = 0.196 in PD-IDC and P = 0.853 in PD-DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD-IDC as well as PD-DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD-DCIS (ICD-O-3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I-III cancer) and was associated with worse survival outcomes than the other type of PD-DCIS.

CONCLUSIONS: Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD-DCIS cases were invasive breast cancer cases that required special treatment.},
}

Aged
Aged, 80 and over
Biomarkers, Tumor
Breast Neoplasms/*epidemiology/etiology/mortality/pathology
Female
Humans
Kaplan-Meier Estimate
Middle Aged
Paget's Disease, Mammary/*epidemiology/etiology/mortality/pathology
Population Surveillance
Prognosis
SEER Program

@article {pmid32209879,
year = {2020},
author = {Liu, Q and Zhang, J and Kulkarni, HR and Baum, RP},
title = {177Lu-DOTATOC Peptide Receptor Radionuclide Therapy in a Patient With Neuroendocrine Breast Carcinoma and Breast Invasive Ductal Carcinoma.},
journal = {Clinical nuclear medicine},
volume = {45},
number = {5},
pages = {e232-e235},
doi = {10.1097/RLU.0000000000003005},
pmid = {32209879},
issn = {1536-0229},
mesh = {Aged ; Bone Neoplasms/secondary ; Breast Neoplasms/pathology/*radiotherapy ; Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/pathology/*radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Neuroendocrine Tumors/diagnostic imaging/metabolism/pathology/*radiotherapy ; Octreotide/*analogs & derivatives/therapeutic use ; Positron Emission Tomography Computed Tomography ; Receptors, Somatostatin/*metabolism ; Treatment Outcome ; },
abstract = {Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)-targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on Ga-DOTATOC PET/CT, and remarkably partial remission after Lu-DOTATOC PRRT.},
}

Aged
Bone Neoplasms/secondary
Breast Neoplasms/pathology/*radiotherapy
Carcinoma, Ductal, Breast/diagnostic imaging/metabolism/pathology/*radiotherapy
Female
Humans
Lymphatic Metastasis
Neuroendocrine Tumors/diagnostic imaging/metabolism/pathology/*radiotherapy
Octreotide/*analogs & derivatives/therapeutic use
Positron Emission Tomography Computed Tomography
Receptors, Somatostatin/*metabolism
Treatment Outcome

@article {pmid32700071,
year = {2020},
author = {Richards, D and Ayala, AA and Wu, Y and Middleton, LP},
title = {Carcinoma In Situ Involving Sclerosing Adenosis on Core Biopsy: Diagnostic Pearls to Aid the Practicing Clinician and Avoid Overtreatment.},
journal = {Oncology and therapy},
volume = {8},
number = {1},
pages = {81-89},
doi = {10.1007/s40487-019-00107-y},
pmid = {32700071},
issn = {2366-1089},
abstract = {INTRODUCTION: Involvement of pre-existing benign lesions by ductal carcinoma in situ (DCIS) or lobular neoplasia (LN) can present difficult diagnostic challenges, and can easily cause misdiagnosis of invasive carcinoma and over-management of localized disease. Our objective was to gather the largest case series of DCIS and LN involving sclerosing adenosis (SA), and to report the characteristic features of these lesions, in order to provide histologic criteria for the diagnostician.

METHODS: Our database was searched for core biopsy material diagnosed as carcinoma in situ involving adenosis. Glass slides and pathology reports were reviewed. The cases were studied for salient features, and clinical follow-up was also obtained.

RESULTS: Thirty-one cases of DCIS or LN involving SA were obtained (12 cases of DCIS, 19 cases of LN including LCIS and ALH). Histomorphologic features commonly seen with DCIS or LN involving SA included lobulocentric architecture (31/31, 100%), myoepithelial cells visible by H&E at least focally (31/31, 100%), and separate areas of SA not involved by neoplasia (29/31, 93.5%). Features that were sometimes seen included hyaline basement membranes surrounding the lesion (14/31, 45.2%), DCIS/LN apart from the area of involvement by SA (16/31, 51.6%), and calcifications associated with DCIS/LN/SA (12/31, 38.7%). Features that were not commonly seen included desmoplasia (6/31, 19.4%), dense inflammation (4/31, 12.9%), and single epithelial cells enveloped by flattened myoepithelial cells (6/31, 19.4%). Of the ten cases of DCIS with known follow-up, four showed DCIS involving either SA or a complex SA on excision (4/10, 40%), four had only DCIS (4/10, 40%), one had DCIS with a small 1.8-mm focus of predominantly tubular carcinoma (1/10, 10%), and one showed invasive ductal carcinoma on excision (1/10, 10%). The latter case of invasive ductal carcinoma occurred in a patient who had a delay of 3 years from diagnosis to surgical resection. Of the eight cases of LN with surgical follow-up, seven had LCIS (7/8, 87.5%), and one showed only fibroadenoma and SA with no residual LN in the excised specimen (1/8, 12.5%). Importantly, no invasive carcinoma was identified in any of the resections for LN involving SA.

CONCLUSIONS: In our series of carcinoma in situ (CIS) involving sclerosing adenosis diagnosed on core biopsy, lobular lesions involving SA were more common than ductal lesions. Ductal and lobular carcinoma in situ involving adenosis were best diagnosed by the low-power appearance of a lobulocentric pattern of growth. The most helpful diagnostic feature was the observation of additional foci of carcinoma in situ away from the adenosis. Immunohistochemical stains for myoepithelial cells were useful in particularly difficult cases. The presence of stromal desmoplasia does not preclude the diagnosis of carcinoma in situ involving adenosis. Knowledge of these diagnostic pearls can reduce over-interpretation of CIS on core biopsy and subsequent overtreatment.},
}

@article {pmid32381867,
year = {2020},
author = {Tamaoki, M and Nio, Y and Tamaoki, M and Sakamoto, M and Uesugi, K and Sakamoto, T and Imai, S and Maruyama, R},
title = {[Radiation-Associated Angiosarcoma That Developed in the Irradiated Residual Breast after Breast-Conserving Surgery for Breast Cancer-A Case Report and Review of the Literature].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {47},
number = {1},
pages = {77-81},
pmid = {32381867},
issn = {0385-0684},
mesh = {Aged ; *Breast Neoplasms/radiotherapy ; Female ; *Hemangiosarcoma/etiology ; Humans ; Japan ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Recurrence, Local ; *Neoplasms, Radiation-Induced ; *Skin Neoplasms ; },
abstract = {We report a radiation-associated angiosarcoma(RAAS)of the breast, which is a rare but important complication after breast-conserving surgery(BCS)and radiotherapy(RT)for breast cancer. A7 2-year-old woman had undergone BCS for invasive ductal carcinoma of the right breast(pT2pN1M0, StageⅡB), followed by RT of 50 Gy; she was treated with doxifluridine and anastrozole for 5 year. She noticed a bloody cutaneous bulla in the right breast 64 months later, and the skin lesions gradually expanded. She was brought to our clinic for the treatment of massive bleeding from the skin lesions. Ulcer biopsy revealed cutaneous AS(cells were CD31[+], CD34[+], VEGF[-], and VEGF-R[+]). She underwent mastectomy and latissimus dorsal flap surgery. She died of local recurrence and liver metastasis 13 months later. RAAS is rare, but it should be considered in patients with skin lesions, such as erosion and bloody bulla, after BCS and RT for breast cancer. To our knowledge, only 12 cases of RAAS, including the present case, have been reported in Japan, and we reviewed the Japanese RAAS cases in comparison with those reported in the Western literature.},
}

Aged
*Breast Neoplasms/radiotherapy
Female
*Hemangiosarcoma/etiology
Humans
Japan
Mastectomy
Mastectomy, Segmental
Neoplasm Recurrence, Local
*Neoplasms, Radiation-Induced
*Skin Neoplasms

@article {pmid31288210,
year = {2019},
author = {Shelef, L and Klomek, AB and Fruchter, E and Kedem, R and Mann, JJ and Zalsman, G},
title = {Suicide ideation severity is associated with severe suicide attempts in a military setting.},
journal = {European psychiatry : the journal of the Association of European Psychiatrists},
volume = {61},
number = {},
pages = {49-55},
doi = {10.1016/j.eurpsy.2019.06.005},
pmid = {31288210},
issn = {1778-3585},
mesh = {Adult ; Female ; Humans ; Intention ; Male ; Middle Aged ; Military Personnel/*psychology ; Risk Factors ; Self Report ; Self-Control/*psychology ; *Severity of Illness Index ; *Suicidal Ideation ; Suicide, Attempted/psychology ; Veterans/*psychology ; Young Adult ; },
abstract = {BACKGROUND: There is an ongoing debate on the effectiveness of suicidal behavior prevention measures in the military. The association of three widely used tools with severe suicide attempts was assessed in this setting.

METHODS: Thirty-nine Israeli soldiers (59% males), mean age 19 yrs., who attempted suicide during military service were divided into two groups: severe (n = 14; 35.9%) and moderate suicide attempts, and were assessed using the Scale for Suicide Ideation (SSI), Suicide Intent Scale (SIS) and the Columbia Suicide Severity Rating Scale (C-SSRS).

RESULTS: Seven items from the SSI (p = 0.008), two items from SIS and one item from C-SSRS were associated with severe suicide attempts. Kendall's tau-b correlation with bootstrap demonstrated stability of these correlations.

CONCLUSION: Greater severity of suicidal ideation was associated with more severe suicide attempts. The combination of male gender, available firearms and current severe suicide ideation is high-risk danger sign in a military setting, even when reported intent to die is low.},
}

Adult
Female
Humans
Intention
Male
Middle Aged
Military Personnel/*psychology
Risk Factors
Self Report
Self-Control/*psychology
*Severity of Illness Index
*Suicidal Ideation
Suicide, Attempted/psychology
Veterans/*psychology
Young Adult

@article {pmid32266446,
year = {2020},
author = {Zong, L and Mo, S and Yu, S and Zhou, Y and Zhang, M and Chen, J and Xiang, Y},
title = {Expression of the immune checkpoint VISTA in breast cancer.},
journal = {Cancer immunology, immunotherapy : CII},
volume = {69},
number = {8},
pages = {1437-1446},
doi = {10.1007/s00262-020-02554-3},
pmid = {32266446},
issn = {1432-0851},
support = {81672648//National Natural Science Foundation of China/International ; 81971475//National Natural Science Foundation of China/International ; CAMS-2017-I2M-1-002//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; CAMS-2016-I2M-1-001//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/International ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; B7 Antigens/*metabolism ; B7-H1 Antigen/*metabolism ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*immunology/*metabolism/pathology ; Carcinoma, Ductal, Breast ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphocytes, Tumor-Infiltrating/*immunology ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/*metabolism ; Survival Rate ; },
abstract = {V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint that is an emerging target for cancer immunotherapy. This study aimed to investigate the expression of VISTA and its association with clinicopathologic parameters as well as with the key immune markers including programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) in invasive ductal carcinoma (IDC) of the breast [corrected]. Immunohistochemistry was used to detect VISTA, PD-1, PD-L1, and CD8 in tissue microarrays from 919 patients with IDC (N = 341 in the exploratory cohort and = 578 in the validation cohort). VISTA was expressed on the immune cells of 29.1% (267/919) of the samples and on the tumor cells of 8.2% (75/919). VISTA was more frequently expressed in samples that were estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2-positive, poorly differentiated, human epidermal growth factor receptor 2-enriched, and consisting of basal-like tumors. VISTA on immune cells correlated with PD-1, PD-L1, stromal CD8, and tumor-infiltrating lymphocyte expression and was an independent prognostic factor for improved relapse-free and disease-specific survival in patients with estrogen receptor-negative, progesterone receptor-negative, and basal-like IDC. These findings support therapeutic strategies that modulate VISTA expression, perhaps in combination with PD-1/PD-L1 blockade, in human breast cancer immunotherapy.},
}

Adult
Aged
Aged, 80 and over
B7 Antigens/*metabolism
B7-H1 Antigen/*metabolism
Biomarkers, Tumor/*metabolism
Breast Neoplasms/*immunology/*metabolism/pathology
Carcinoma, Ductal, Breast
Cohort Studies
Female
Gene Expression Regulation, Neoplastic
Humans
Lymphocytes, Tumor-Infiltrating/*immunology
Middle Aged
Prognosis
Programmed Cell Death 1 Receptor/*metabolism
Survival Rate

@article {pmid32007118,
year = {2019},
author = {Komaei, I and Guccione, F and Sarra, F and Palmeri, E and Ieni, A and Cardia, R and Currò, G and Navarra, G and Palmeri, R},
title = {Radiation-induced undifferentiated pleomorphic sarcoma of the breast: a rare but serious complication following breast-conserving therapy. A case report and literature review.},
journal = {Il Giornale di chirurgia},
volume = {40},
number = {6},
pages = {544-550},
pmid = {32007118},
issn = {1971-145X},
mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/*etiology/pathology/radiotherapy/surgery ; Carcinoma, Ductal, Breast/drug therapy/*radiotherapy/surgery ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Diagnosis, Differential ; Epirubicin/administration & dosage ; Female ; Humans ; Letrozole/administration & dosage ; Mastectomy ; *Mastectomy, Segmental ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis ; Neoplasms, Radiation-Induced/diagnosis/*etiology/pathology/therapy ; Photons ; Radiotherapy, High-Energy/*adverse effects ; Sarcoma/diagnosis/*etiology/pathology/therapy ; Ultrasonography, Mammary ; },
abstract = {BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) of the breast is an extremely rare, but aggressive subtype of sarcoma that can develop in radiotherapy (RT)-treated breast cancer patients. Due to the low incidence, there are many uncertainties regarding the adequate management of these tumors. We present a rare case of radiation-induced UPS in a 63-year-old woman who had undergone breast conserving therapy for invasive ductal carcinoma of the left breast, six years prior to presentation.

CASE PRESENTATION: A 63-year-old woman presented with a rapidly growing left breast mass. She had been diagnosed with invasive ductal carcinoma of the left breast for which she underwent a left upper outer quadrantectomy and ipsilateral axillary dissection followed by RT, six years previously. During her routine oncologic follow-up, the mammography revealed a dense, nodular opacity with microcalcifications. The breast ultrasound (US) confirmed the presence of the nodule. US-guided fine needle aspiration biopsy was performed and the diagnosis of UPS was made, the reason for which the patient underwent wide local excision of the left breast.

CONCLUSION: The diagnosis of RT-induced UPS is challenging and often missed due to the low incidence, long latency period, unspecific imaging findings, and difficulties in clinical and histological detection of these lesions. These tumors should be considered in differential diagnoses of rapidly-growing breast masses in previously RT-treated breast cancer patients, as they can mimic the local recurrence of the primary tumor. Since the prevalence of breast-conserving surgery followed by RT has been increasing, the careful monitoring of at risk patients is of utmost importance, as UPSs are highly aggressive tumors associated with very poor outcomes.},
}

Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Biomarkers, Tumor
Breast Neoplasms/*etiology/pathology/radiotherapy/surgery
Carcinoma, Ductal, Breast/drug therapy/*radiotherapy/surgery
Chemotherapy, Adjuvant
Combined Modality Therapy
Cyclophosphamide/administration & dosage
Diagnosis, Differential
Epirubicin/administration & dosage
Female
Humans
Letrozole/administration & dosage
Mastectomy
*Mastectomy, Segmental
Middle Aged
Neoplasm Recurrence, Local/diagnosis
Neoplasms, Radiation-Induced/diagnosis/*etiology/pathology/therapy
Photons
Radiotherapy, High-Energy/*adverse effects
Sarcoma/diagnosis/*etiology/pathology/therapy
Ultrasonography, Mammary

@article {pmid32665190,
year = {2020},
author = {Escott, CE and Zaenger, D and Switchencko, JM and Lin, JY and Abugideiri, M and Arciero, CA and Pfister, NT and Xu, KM and Meisel, JL and Subhedar, P and Torres, M and Curran, WJ and Patel, PR},
title = {The Influence of Histologic Grade on Outcomes of Elderly Women With Early Stage Breast Cancer Treated With Breast Conserving Surgery With or Without Radiotherapy.},
journal = {Clinical breast cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clbc.2020.05.007},
pmid = {32665190},
issn = {1938-0666},
abstract = {BACKGROUND: Two large randomized trials, CALGB 9343 and PRIME II, support omission of radiotherapy after breast conserving surgery (BCS) in elderly women with favorable-risk early stage breast cancer intending to take endocrine therapy. However, patients with grade 3 histology were underrepresented on these trials. We hypothesized that high-grade disease may be unsuitable for treatment de-escalation and report the oncologic outcomes for elderly women with favorable early stage breast cancer treated with BCS with or without radiotherapy.

MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for women between 70 and 79 years of age with invasive ductal carcinoma diagnosed between 1998 and 2007. This cohort was narrowed to women with T1mic-T1c, N0, estrogen receptor-positive, invasive ductal carcinoma treated with BCS with or without external beam radiation (EBRT). The primary endpoints were 5- and 10-year cause-specific survival (CSS). Univariate and multivariate analyses were performed. Propensity-score matching of T-stage, year of diagnosis, and age was utilized to reduce selection bias while comparing treatment arms within the grade 3 subgroup.

RESULTS: A total of 12,036 women met inclusion criteria, and the median follow-up was 9.4 years. EBRT was omitted in 22% of patients, including 21% with grade 3 disease. Patients in the EBRT cohort were slightly younger (median, 74 vs. 75 years; P < .01) and had fewer T1a tumors (11% vs. 13%; P = .02). Histologic grades 1, 2, and 3 comprised 36%, 50%, and 14% of the cohort, respectively, and there were no differences in EBRT utilization by grade. Utilization of EBRT decreased following the publication of the CALGB trial in 2004 decreasing from 82% to 85% in 1998 to 2000 to 73% to 75% in 2005 to 2007 (P < .01). Unadjusted outcomes showed that in grade 1 disease, there were no differences in CSS with or without EBRT at 5 (99%) and 10 years (95%-96%). EBRT was associated with an improvement in CSS in grade 2 histology at 5 years (97% vs. 98%) and 10 years (92% vs. 95%) (P = .004). The benefit was more pronounced in grade 3 disease with CSS increasing from 93% to 96% at 5 years and from 87% to 92% at 10 years (P = .02) with EBRT. In the grade 3 subgroup, propensity-score matching confirmed EBRT was associated with superior CSS compared with surgery alone (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P = .043).

CONCLUSION: In this database analysis, omission of radiotherapy after BCS in elderly women with favorable-risk, early stage, grade 3 breast cancer was associated with inferior CSS. Further prospective data in this patient population are needed to confirm our findings and conclusions.},
}

@article {pmid31299411,
year = {2019},
author = {Molina, J and Noguer, M and Lepe, JA and Pérez-Moreno, MA and Aguilar-Guisado, M and Lasso de la Vega, R and Peñalva, G and Crespo-Rivas, JC and Gil-Navarro, MV and Salvador, J and Cisneros, JM},
title = {Clinical impact of an educational antimicrobial stewardship program associated with infectious diseases consultation targeting patients with cancer: Results of a 9-year quasi-experimental study with an interrupted time-series analysis.},
journal = {The Journal of infection},
volume = {79},
number = {3},
pages = {206-211},
doi = {10.1016/j.jinf.2019.07.002},
pmid = {31299411},
issn = {1532-2742},
mesh = {*Anti-Bacterial Agents/therapeutic use ; *Antimicrobial Stewardship ; Communicable Diseases/drug therapy/*epidemiology/etiology ; Drug Utilization/statistics & numerical data ; Female ; Health Plan Implementation ; Humans ; Male ; Neoplasms/complications/*epidemiology ; *Referral and Consultation ; Time Factors ; },
abstract = {OBJECTIVES: Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. However, their effectiveness or safety in immunocompromised hosts needs to be proved.

METHODS: An ecologic quasi-experimental study was performed from January 2009 to June 2017 in the Oncology department of a tertiary-care hospital. A stable program of Infectious Diseases consultation (IDC) already existed at this unit, and an educational ASP was added in 2011. Its main intervention consisted of face-to-face educational interviews. Antibiotic consumption was assessed through quarterly Defined Daily Doses (DDD) per 100 occupied bed-days. Mortality was evaluated in patients with bloodstream infections through the quarterly incidence density per 1000 admissions, and the annual mortality rates at 7 and 30-days. Time-trends were analysed through segmented-regression analysis, and the impact of the ASP was assessed through before-after interrupted time-series analysis.

RESULTS: Mortality significantly decreased throughout the study period (-13.3% annual reduction for 7-day mortality rate, p < 0.01; -8.1% annual reduction for 30-day mortality, p = 0.03), parallel to a reduction in antibiotic consumption (quarterly reduction -0.4%, p = 0.01), especially for broader-spectrum antibiotics. The before-after study settled a significant inflexion point on the ASP implementation for the reduction of antibiotic consumption (change in level 0.95 DDD, p = 0.71; change in slope -1.98 DDD per quarter, p < 0.01). The decreasing trend for mortality before the ASP also continued after its implementation.

CONCLUSIONS: The combination of an ASP with IDC improved antibiotic use among patients with cancer, and was accompanied by a reduction of mortality of bacteraemic infections. Implementation of the ASP was necessary to effectively change antibiotic use.},
}

*Anti-Bacterial Agents/therapeutic use
*Antimicrobial Stewardship
Communicable Diseases/drug therapy/*epidemiology/etiology
Drug Utilization/statistics & numerical data
Female
Health Plan Implementation
Humans
Male
Neoplasms/complications/*epidemiology
*Referral and Consultation
Time Factors

@article {pmid32637252,
year = {2020},
author = {Jones, B and Thomas, G and Westreich, J and Nofech-Mozes, S and Vitkin, A and Khorasani, M},
title = {Novel quantitative signature of tumor stromal architecture: polarized light imaging differentiates between myxoid and sclerotic human breast cancer stroma.},
journal = {Biomedical optics express},
volume = {11},
number = {6},
pages = {3246-3262},
doi = {10.1364/BOE.392722},
pmid = {32637252},
issn = {2156-7085},
abstract = {As a leading cause of death in women, breast cancer is a global health concern for which personalized therapy remains largely unrealized, resulting in over- or under-treatment. Recently, tumor stroma has been shown to carry important prognostic information, both in its relative abundance and morphology, but its current assessment methods are few and suboptimal. Herein, we present a novel stromal architecture signature (SAS) methodology based on polarized light imaging that quantifies patterns of tumor connective tissue. We demonstrate its ability to differentiate between myxoid and sclerotic stroma, two pathology-derived categories associated with significantly different patient outcomes. The results demonstrate a 97% sensitivity and 88% specificity for myxoid stroma identification in a pilot study of 102 regions of interest from human invasive ductal carcinoma breast cancer surgical specimens (20 patients). Additionally, the SAS numerical score is indicative of the wide range of stromal characteristics within these binary classes and highlights ambiguous mixed-morphology regions prone to misclassification. The enabling polarized light microscopy technique is inexpensive, fast, fully automatable, applicable to fresh or embedded tissue without the need for staining and thus potentially translatable into research and/or clinical settings. The SAS metric yields quantifiable and objective stromal characterization with promise for prognosis in many types of cancers beyond breast carcinoma, enabling researchers and clinicians to further investigate the emerging and important role of stromal architectural patterns in solid tumors.},
}

@article {pmid32618211,
year = {2020},
author = {Bhattad, PB and Jain, V},
title = {Diffuse Sarcoidosis Masquerading as Widespread Malignant Disease: A Rare Case Report and Literature Review.},
journal = {Journal of investigative medicine high impact case reports},
volume = {8},
number = {},
pages = {2324709620938942},
doi = {10.1177/2324709620938942},
pmid = {32618211},
issn = {2324-7096},
abstract = {Sarcoidosis is a multisystem granulomatous disease commonly involving the lungs and mediastinal lymph nodes with the exact etiology being unclear. The simultaneous presence of malignant disease such as breast cancer and sarcoidosis has been reported. Sarcoidosis preceding a diagnosis of malignancy and that occurring years after treatment of malignant disease has been noted in the past. The presence of sarcoidosis in the setting of malignant disease carries a high risk of misdiagnosis. In this article, we report the case of a 45-year-old female with stage IA invasive ductal carcinoma of left breast that was in remission for 2 years; however, radiological imaging including magnetic resonance imaging of thoracic spine and positron emission tomography-computed tomography scanning were highly suspicious for malignant disease metastasis versus lymphoma with the widespread lymphadenopathy. Multiple tissue biopsies with histopathological evaluation allowed us to definitively exclude malignant disease metastasis and to correctly diagnose her atypical presentation of sarcoidosis.},
}

@article {pmid30372658,
year = {2019},
author = {Steger, M and Bermejo-Jambrina, M and Yordanov, T and Wagener, J and Brakhage, AA and Pittl, V and Huber, LA and Haas, H and Lass-Flörl, C and Posch, W and Wilflingseder, D},
title = {β-1,3-glucan-lacking Aspergillus fumigatus mediates an efficient antifungal immune response by activating complement and dendritic cells.},
journal = {Virulence},
volume = {10},
number = {1},
pages = {957-969},
doi = {10.1080/21505594.2018.1528843},
pmid = {30372658},
issn = {2150-5608},
mesh = {Aspergillosis/microbiology ; Aspergillus fumigatus/*chemistry/genetics/*immunology ; *Complement Activation ; Cytokines/immunology ; Dendritic Cells/*immunology ; Echinocandins/therapeutic use ; Humans ; Immunity, Innate ; Mutation ; Spores, Fungal/immunology ; THP-1 Cells ; *beta-Glucans ; },
abstract = {Complement system and dendritic cells (DCs) form - beside neutrophils and macrophages - the first line of defense to combat fungal infections. Therefore, we here studied interactions of these first immune elements with Aspergillus fumigatus lacking ß-1,3-glucans (fks1tetOnrep under repressed conditions) to mechanistically explain the mode of action of echinocandins in more detail. Echinocandins are cell wall active agents blocking β-glucan synthase, making the A. fumigatus fks1tetOn mutant a good model to study immune-modulatory actions of these drugs. We now demonstrate herein, that complement was activated to significantly higher levels by the fks1-deficient strain compared to its respective wild type. This enhanced covalent linking of complement fragments to the A. fumigatus fks1tetOnrep mutant further resulted in enhanced DC binding and internalization of the fungus. Additionally, we found that fks1tetOnrep induced a Th1-/Th17-polarizing cytokine profile program in DCs. The effect was essentially dependent on massive galactomannan shedding, since blocking of DC-SIGN significantly reduced the fks1tetOnrep-mediated induction of an inflammatory cytokine profile.Our data demonstrate that lack of ß-1,3-glucan, also found under echinocandin therapy, results in improved recognition of Aspergillus fumigatus by complement and DCs and therefore not only directly affects the fungus by its fungistatic actions, but also is likely to exert indirect antifungal mechanisms by strengthening innate host immune mechanisms.Abbreviations: C: complement; CR:complement receptor; DC: dendritic cell; iDC: immature dendritic cell; DC-SIGN: Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; ERK: extracellular signal-regulated kinases; JNK : c-Jun N-terminal kinases; MAPK: mitogen-activated protein kinase; NHS: normal human serum; PRR: pattern recognition receptor; Th :T helper; TLR :Toll-like receptor; WT: wild type.},
}

Aspergillosis/microbiology
Aspergillus fumigatus/*chemistry/genetics/*immunology
*Complement Activation
Cytokines/immunology
Dendritic Cells/*immunology
Echinocandins/therapeutic use
Humans
Immunity, Innate
Mutation
Spores, Fungal/immunology
THP-1 Cells
*beta-Glucans

@article {pmid32585364,
year = {2020},
author = {Erener, S},
title = {Diabetes, Infection Risk And Covid-19.},
journal = {Molecular metabolism},
volume = {},
number = {},
pages = {101044},
doi = {10.1016/j.molmet.2020.101044},
pmid = {32585364},
issn = {2212-8778},
abstract = {BACKGROUND: Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial and fungal infections. The Coronavirus Disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries across the world and has claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19.

SCOPE OF REVIEW: In this review, I will summarize the clinical data on the risk for infectious diseases in individuals with diabetes, highlighting the mechanisms for altered immune regulation. A special focus will be given to coronaviruses. In the light of the new clinical data obtained from COVID-19 patients, mechanisms such as cytokine storm, pulmonary and endothelial dysfunction, hypercoagulation that may render individuals with diabetes more vulnerable to COVID-19 will be discussed in the end.

MAJOR CONCLUSIONS: Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to design tailored treatments and clinical management of individuals affected by diabetes.},
}

@article {pmid32563094,
year = {2020},
author = {Yoneyama, K and Nakagawa, M and Hara, A},
title = {Local recurrence of breast cancer caused by core needle biopsy: Case report and review of the literature.},
journal = {International journal of surgery case reports},
volume = {72},
number = {},
pages = {318-321},
doi = {10.1016/j.ijscr.2020.06.013},
pmid = {32563094},
issn = {2210-2612},
abstract = {INTRODUCTION: Needle tract seeding is the implantation of tumor cells at the site of needle passage during needle biopsy. Histopathological examination of resected specimens after biopsy shows an incidence of 22%-50%. However, reports of actual local recurrence are extremely rare. Here we report such a case.

PRESENTATION OF CASE: A 67-year-old woman was diagnosed with ductal carcinoma by histopathology and underwent right mastectomy and sentinel lymph node biopsy. Histopathological examination revealed non-invasive ductal carcinoma. One year after the first operation, a mass was found at the site of the core needle biopsy (CNB) scar near the previous surgical wound on the right chest. Histological examination revealed the tumor as adenocarcinoma, and a skin lesion resection was performed. After surgery, radiation therapy and endocrine therapy were performed. She remains relapse-free as of this writing, 9 months after resection.

DISCUSSION: Reports of local recurrence due to needle tract seeding are extremely rare. We found nine cases of mastectomy and seven cases of partial resection performed for the first surgery; six patients received radiation therapy and 10 did not. Histological diagnosis at the time of the first operation was invasive carcinoma in all cases.

CONCLUSION: The risk of seeding is high with multiple punctures in CNB, in cases with a short period until surgery, and in mucinous carcinoma. Considering these factors, CNB puncture should preferably be at a site that is included in the resection area during surgery. If not resected, close follow-up is necessary considering the possibility of local recurrence.},
}

@article {pmid31672492,
year = {2020},
author = {Kim, JE and Kim, BG and Jang, Y and Kang, S and Lee, JH and Cho, NH},
title = {The stromal loss of miR-4516 promotes the FOSL1-dependent proliferation and malignancy of triple negative breast cancer.},
journal = {Cancer letters},
volume = {469},
number = {},
pages = {256-265},
doi = {10.1016/j.canlet.2019.10.039},
pmid = {31672492},
issn = {1872-7980},
mesh = {Antineoplastic Agents/pharmacology ; Cancer-Associated Fibroblasts/metabolism/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/drug effects/genetics ; Disease Progression ; Exosome Multienzyme Ribonuclease Complex/genetics ; Exosomes/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MicroRNAs/*genetics ; Proto-Oncogene Proteins c-fos/*genetics ; Stromal Cells/metabolism/pathology ; Triple Negative Breast Neoplasms/*drug therapy/genetics/pathology ; },
abstract = {Stroma-derived exosomal microRNA (exomiR) contributes to tumor progression, however, which remains poorly understood. In our study, we analyzed exomiRs from the cancer-associated fibroblast (CAF) and normal fibroblast (NF) isolated from an invasive ductal carcinoma (IDC) patient and found that the level of microRNA (miR)-4516 was approximately 5-fold lower in CAF-derived exosomes than NF-derived ones. In gene annotation analysis, miR-4516 target genes were mainly associated with the regulation of proliferation. miR-4516 overexpression or mimic treatment suppressed the proliferation of breast cancer cells, especially triple negative breast cancer (TNBC) cells. Among miR-4516 targets, FOSL1 was overexpressed in TNBC cells compared to non-TNBC cells and promoted tumor proliferation. The expression of miR-4516 and FOSL1 was reversely correlated in breast cancer patient tissues. Particularly, TNBC patients with high FOSL1 expression showed a significant poorer survival than those with low FOSL1 expression. Our results show that the loss of miR-4516 from CAF-derived exosomes is associated with FOSL1-dependent TNBC progression and suggest that miR-4516 can be used as an anti-cancer drug for TNBC.},
}

Antineoplastic Agents/pharmacology
Cancer-Associated Fibroblasts/metabolism/pathology
Cell Line, Tumor
Cell Movement/genetics
Cell Proliferation/drug effects/genetics
Disease Progression
Exosome Multienzyme Ribonuclease Complex/genetics
Exosomes/genetics/metabolism
Female
Gene Expression Regulation, Neoplastic/drug effects
Humans
MicroRNAs/*genetics
Proto-Oncogene Proteins c-fos/*genetics
Stromal Cells/metabolism/pathology
Triple Negative Breast Neoplasms/*drug therapy/genetics/pathology

@article {pmid32548206,
year = {2020},
author = {Arensman, K and Dela-Pena, J and Miller, JL and LaChance, E and Beganovic, M and Anderson, M and Rivelli, A and Wieczorkiewicz, SM},
title = {Impact of Mandatory Infectious Diseases Consultation and Real-time Antimicrobial Stewardship Pharmacist Intervention on Staphylococcus aureus Bacteremia Bundle Adherence.},
journal = {Open forum infectious diseases},
volume = {7},
number = {6},
pages = {ofaa184},
doi = {10.1093/ofid/ofaa184},
pmid = {32548206},
issn = {2328-8957},
abstract = {Background: The purpose of this study was to evaluate the impact of infectious diseases consultation (IDC) and a real-time antimicrobial stewardship (AMS) review on the management of Staphylococcus aureus bacteremia (SAB).

Methods: This retrospective study included adult inpatients with SAB from January 2016 to December 2018 at 7 hospitals. Outcomes were compared between 3 time periods: before mandatory IDC and AMS review (period 1), after mandatory IDC and before AMS review (period 2), and after mandatory IDC and AMS review (period 3). The primary outcome was bundle adherence, defined as appropriate intravenous antimicrobial therapy, appropriate duration of therapy, appropriate surveillance cultures, echocardiography, and removal of indwelling intravenous catheters, if applicable. Secondary end points included individual bundle components, source control, length of stay (LOS), 30-day bacteremia-related readmission, and in-hospital all-cause mortality.

Results: A total of 579 patients met inclusion criteria for analysis. Complete bundle adherence was 65% in period 1 (n = 241/371), 54% in period 2 (n = 47/87), and 76% in period 3 (n = 92/121). Relative to period 3, bundle adherence was significantly lower in period 1 (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.37-0.93; P = .02) and period 2 (OR, 0.37; 95% CI, 0.20-0.67; P = .0009). No difference in bundle adherence was noted between periods 1 and 2. Significant differences were seen in obtaining echocardiography (91% vs 83% vs 100%; P < .001), source control (34% vs 45% vs 45%; P = .04), and hospital LOS (10.5 vs 8.9 vs 12.0 days; P = .01). No differences were noted for readmission or mortality.

Conclusions: The addition of AMS pharmacist review to mandatory IDC was associated with significantly improved quality care bundle adherence.},
}

@article {pmid31016756,
year = {2019},
author = {Zenan, H and Zixiong, L and Zhicheng, Y and Mei, H and Xiongbin, Y and Tiantian, W and Min, D and Renbin, L and Changchang, J},
title = {Clinical prognostic evaluation of immunocytes in different molecular subtypes of breast cancer.},
journal = {Journal of cellular physiology},
volume = {234},
number = {11},
pages = {20584-20602},
doi = {10.1002/jcp.28662},
pmid = {31016756},
issn = {1097-4652},
mesh = {Aging ; Biomarkers, Tumor ; Blood Platelets/classification/physiology ; Breast Neoplasms/*classification/*genetics/pathology ; Cohort Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Leukocytes/*classification/*physiology ; Logistic Models ; Middle Aged ; Prognosis ; Receptor, ErbB-2/genetics/*metabolism ; Retrospective Studies ; Triple Negative Breast Neoplasms/*pathology ; },
abstract = {To retrospectively analyze the relationship between preoperative blood parameters and postoperative clinical outcomes in patients with different molecular subtypes of breast cancer (BC), a cohort of 601 patients with BC in the Third Affiliated Hospital, Sun Yat-sen University, was retrospectively reviewed. They were categorized into four subtypes according to the expression of ER, PR, HER-2, and KI-67%. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts, the neutrophil-to-lymphocyte ratio (NLR), the neutrophil-to-monocyte ratio (NMR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR) were recorded. Univariate and multivariate analyses were performed to identify the relationship between parameters and ratios and disease-free survival (DFS) and overall survival (OS). Luminal subtypes of BC had smaller tumor volume, better differentiation degree of invasive ductal carcinoma, less lymph node metastasis, and better clinical outcome than the HER-2 overexpression and triple-negative BC (TNBC) subtypes. In multivariate analysis, age and LMR were the independent prognostic factors of DFS in patients with luminal A (age, p = 0.005; LMR, P = 0.026); PLR in patients with luminal B (DFS; p = 0.032; OS, p= 0.012); LMR in patients with HER-2 overexpression (DFS; p = 0.008; OS, p = 0.017); and NLR for DFS (p = 0.014); and WBC for OS (p = 0.008) in patients with TNBC. LMR was the benign predictor of luminal A and HER-2 overexpression. PLR was the adverse predictor of luminal B. WBC and NLR were the adverse predictors of TNBC. Therefore, these peripheral blood parameters can play an important role in the diagnosis and treatment of patients with different molecular subtypes of BC.},
}

Aging
Biomarkers, Tumor
Blood Platelets/classification/physiology
Breast Neoplasms/*classification/*genetics/pathology
Cohort Studies
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Leukocytes/*classification/*physiology
Logistic Models
Middle Aged
Prognosis
Receptor, ErbB-2/genetics/*metabolism
Retrospective Studies
Triple Negative Breast Neoplasms/*pathology

@article {pmid30772465,
year = {2019},
author = {Ducommun, S and Deak, M and Zeigerer, A and Göransson, O and Seitz, S and Collodet, C and Madsen, AB and Jensen, TE and Viollet, B and Foretz, M and Gut, P and Sumpton, D and Sakamoto, K},
title = {Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates.},
journal = {Cellular signalling},
volume = {57},
number = {},
pages = {45-57},
doi = {10.1016/j.cellsig.2019.02.001},
pmid = {30772465},
issn = {1873-3913},
mesh = {AMP-Activated Protein Kinases/*metabolism ; Animals ; Guanine Nucleotide Exchange Factors/*metabolism ; Hepatocytes/metabolism ; Homeostasis/genetics/physiology ; Lipid Metabolism/genetics ; Liver/*metabolism ; Mass Spectrometry/methods ; Membrane Proteins/*metabolism ; Mice, Knockout ; Muscle Proteins/*metabolism ; Phosphorylation ; Substrate Specificity ; },
abstract = {AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis, acting as a sensor of energy and nutrient status. As such, AMPK is considered a promising drug target for treatment of medical conditions particularly associated with metabolic dysfunctions. To better understand the downstream effectors and physiological consequences of AMPK activation, we have employed a chemical genetic screen in mouse primary hepatocytes in an attempt to identify novel AMPK targets. Treatment of hepatocytes with a potent and specific AMPK activator 991 resulted in identification of 65 proteins phosphorylated upon AMPK activation, which are involved in a variety of cellular processes such as lipid/glycogen metabolism, vesicle trafficking, and cytoskeleton organisation. Further characterisation and validation using mass spectrometry followed by immunoblotting analysis with phosphorylation site-specific antibodies identified AMPK-dependent phosphorylation of Gapex-5 (also known as GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1)) on Ser902 in hepatocytes and starch-binding domain 1 (STBD1) on Ser175 in multiple cells/tissues. As new promising roles of AMPK as a key metabolic regulator continue to emerge, the substrates we identified could provide new mechanistic and therapeutic insights into AMPK-activating drugs in the liver.},
}

AMP-Activated Protein Kinases/*metabolism
Animals
Guanine Nucleotide Exchange Factors/*metabolism
Hepatocytes/metabolism
Homeostasis/genetics/physiology
Lipid Metabolism/genetics
Liver/*metabolism
Mass Spectrometry/methods
Membrane Proteins/*metabolism
Mice, Knockout
Muscle Proteins/*metabolism
Phosphorylation
Substrate Specificity

@article {pmid31351155,
year = {2019},
author = {Ding, Q and Chen, H and Lim, B and Damodaran, S and Chen, W and Tripathy, D and Piha-Paul, S and Luthra, R and Meric-Bernstam, F and Sahin, AA},
title = {HER2 somatic mutation analysis in breast cancer: correlation with clinicopathological features.},
journal = {Human pathology},
volume = {92},
number = {},
pages = {32-38},
doi = {10.1016/j.humpath.2019.07.006},
pmid = {31351155},
issn = {1532-8392},
mesh = {Breast/*pathology ; Breast Neoplasms/*genetics/metabolism/pathology ; Carcinoma, Ductal, Breast/*genetics/metabolism/pathology ; Carcinoma, Lobular/*genetics/metabolism/pathology ; DNA Mutational Analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Receptor, ErbB-2/*genetics/metabolism ; Retrospective Studies ; },
abstract = {HER2 mutations have been reported in approximately 2% of breast cancers. Regardless of HER2 overexpression or amplification status, breast cancer with HER2 mutations may respond to HER2-targeted therapy. As HER2 mutation is rare, the clinical and pathological features of HER2-mutated breast cancers, such as hormonal status, histological grade, and metastasis, remain poorly defined. Therefore, the identification of HER2-mutated breast cancer has clinical significance. We retrospectively screened patients with metastatic breast cancer in whom molecular profiling had been performed using next-generation sequencing from 2012 to 2015; we identified 18 patients with HER2 mutation. Mutations were found on next-generation sequencing-based panels, including Ion AmpliSeq Cancer Hotspot, Oncomine, FoundationOne, and Guardant360. HER2 mutations were identified in both the tyrosine kinase (n = 14) and extracellular (n = 4) domains. Of the 14 cases with tyrosine kinase domain mutations, 13 were estrogen receptor positive; the 4 cases with extracellular domain mutations were exclusively estrogen receptor negative. In addition, 11 of 14 patients with tyrosine kinase domain mutations had bone metastasis, whereas no patients with HER2 extracellular domain mutations had bone metastasis. Histologically, 13 patients had invasive ductal carcinoma, 1 had metaplastic carcinoma, and 4 had invasive lobular carcinoma (ILC). All 4 ILCs were high grade and pleomorphic, and not only had an HER2 mutation in the kinase domain but also had an HER2 mutation involving the L755 site. Specific mutation sites may be involved in the pathogenesis of nonclassic ILC.},
}

Breast/*pathology
Breast Neoplasms/*genetics/metabolism/pathology
Carcinoma, Ductal, Breast/*genetics/metabolism/pathology
Carcinoma, Lobular/*genetics/metabolism/pathology
DNA Mutational Analysis
Female
High-Throughput Nucleotide Sequencing
Humans
Receptor, ErbB-2/*genetics/metabolism
Retrospective Studies

@article {pmid32509097,
year = {2020},
author = {Lv, X and Ye, J and Jiang, G and Wang, Y and Lv, J and Wang, Y},
title = {Simultaneous multiple primary cancers with concomitant inflammatory myofibroblastic tumor: a case report.},
journal = {International journal of clinical and experimental pathology},
volume = {13},
number = {5},
pages = {1212-1215},
pmid = {32509097},
issn = {1936-2625},
abstract = {Multiple primary cancers are of rare occurrence. Most multiple primary cancers are metachronous multiple primary cancers, while simultaneous multiple primary cancers are rare. Inflammatory myofibroblastic tumors are rare. Inflammatory myofibroblastic tumor occurs most frequently in children and young adults. Herein, we report a rare case of simultaneous multiple primary cancers and inflammatory myofibroblastic tumor. A 44-year-old woman was admitted for a breast mass evaluation. The patient was positive for antinuclear, anti-mitochondrial, and anti-RO52 antibodies. Breast magnetic resonance imaging revealed a right breast mass. After neoadjuvant chemotherapy, modified radical mastectomy was performed. Postoperative histopathology revealed an invasive ductal carcinoma. Two months later, computed tomography revealed a nodule in the right upper lobe and ground-glass opacity in the lower lobe of the lungs. Lobectomy and lobe biopsy were performed. Postoperative histopathology revealed that the mass in the right upper lobe was an inflammatory myofibroblastic tumor and the right lower lobe lesion was an invasive adenocarcinoma. Immunohistochemistry of the inflammatory myofibroblastic tumor revealed negativity for anaplastic lymphoma kinase. At the 4-month follow-up, the patient showed good recovery. The etiology of multiple primary cancers and inflammatory myofibroblastic tumors is still unknown; in this case, we believe that autoimmune factors are the main cause of multiple primary cancers with concomitant inflammatory myofibroblastic tumor. Tissue biopsy is needed to ensure correct diagnosis of multiple primary cancers and inflammatory myofibroblastic tumor. Surgery-based comprehensive therapy is recommended. The prognosis is favorable and regular follow-up is necessary.},
}

@article {pmid32408270,
year = {2020},
author = {Pedro, J and Cunha, FM and Neto, V and Hespanhol, V and Martins, DF and Guimarães, S and Varela, A and Carvalho, D},
title = {Coexistence of DIPNECH and carotid body paraganglioma: is it just a coincidence?.},
journal = {Endocrinology, diabetes & metabolism case reports},
volume = {2020},
number = {},
pages = {},
doi = {10.1530/EDM-19-0141},
pmid = {32408270},
issn = {2052-0573},
abstract = {Summary: We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up.

Learning points: The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology. To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma. The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.},
}

@article {pmid32380439,
year = {2020},
author = {Rodriguez-Ibarria, NG and Pinar, MB and García, L and Cabezón, MA and Lloret, M and Rey-Baltar, MD and Rdguez-Melcón, JI and Lara, PC},
title = {Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer.},
journal = {Breast (Edinburgh, Scotland)},
volume = {52},
number = {},
pages = {45-49},
doi = {10.1016/j.breast.2020.04.008},
pmid = {32380439},
issn = {1532-3080},
abstract = {Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008-December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3-1.9) and 98.3% (95% CI 97.3-99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.},
}

@article {pmid32365829,
year = {2020},
author = {Cortes-Urrea, C and Bueno-Gutiérrez, F and Solarte, M and Guevara-Burbano, M and Tobar-Tosse, F and Vélez-Varela, PE and Bonilla, JC and Barreto, G and Velasco-Medina, J and Moreno, PA and Rivas, JL},
title = {Exomes of Ductal Luminal Breast Cancer Patients from Southwest Colombia: Gene Mutational Profile and Related Expression Alterations.},
journal = {Biomolecules},
volume = {10},
number = {5},
pages = {},
doi = {10.3390/biom10050698},
pmid = {32365829},
issn = {2218-273X},
support = {PI18/00591//Instituto de Salud Carlos III/ ; },
abstract = {Cancer is one of the leading causes of mortality worldwide. Breast cancer is the most frequent cancer in women, and in recent years it has become a serious public health problem in Colombia. The development of large-scale omic techniques allows simultaneous analysis of all active genes in tumor cells versus normal cells, providing new ways to discover the drivers of malignant transformations. Whole exome sequencing (WES) was obtained to provide a deep view of the mutational genomic profile in a set of cancer samples from Southwest Colombian women. WES was performed on 52 tumor samples from patients diagnosed with invasive breast cancer, which in most cases (33/52) were ductal luminal breast carcinomas (IDC-LM-BRCA). Global variant call was calculated, and six different algorithms were applied to filter out false positives and identify pathogenic variants. To compare and expand the somatic tumor variants found in the Colombian cohort, exome mutations and genome-wide expression alterations were detected in a larger set of tumor samples of the same breast cancer subtype from TCGA (that included DNA-seq and RNA-seq data). Genes with significant changes in both the mutational and expression profiles were identified, providing a set of genes and mutations associated with the etiology of ductal luminal breast cancer. This set included 19 single mutations identified as tumor driver mutations in 17 genes. Some of the genes (ATM, ERBB3, ESR1, TP53) are well-known cancer genes, while others (CBLB, PRPF8) presented driver mutations that had not been reported before. In the case of the CBLB gene, several mutations were identified in TCGA IDC-LM-BRCA samples associated with overexpression of this gene and repression of tumor suppressive activity of TGF-β pathway.},
}

@article {pmid32317515,
year = {2020},
author = {Pyla, RD and Potekar, RM and Patil, VS and Reddy, AK and Sathyashree, KV},
title = {Quantitative mast cell analysis and hormone receptor study (ER, PR and HER2/neu) in invasive carcinoma of breast.},
journal = {Indian journal of pathology & microbiology},
volume = {63},
number = {2},
pages = {200-204},
doi = {10.4103/IJPM.IJPM_155_19},
pmid = {32317515},
issn = {0974-5130},
abstract = {Context: Breast cancer constitutes nearly one third of cancers among women. Immune responses caused by neoplastic cells lead to the accumulation of inflammatory cells like mast cells (MCs), macrophages, lymphocytes, and plasma cells around the tumor tissue forming the tumor microenvironment.

Aim: The study aims at quantifying the role of MCs in different grades of invasive carcinoma of breast with respect to estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2/neu).

Materials and Methods: This study included 60 cases of invasive carcinoma of breast. Toluidine blue staining was used for quantitative MC analysis and correlated with immunohistochemistry analysis for hormonal markers' positivity-ER, PR and HER2/neu.

Results: The mean age was 52 years (range: 25-75 years). The average number of MCs in Grade I, II, and III were 24.05, 18.4, and 7.9, respectively, with a significant P value. ER, PR, and HER2/neu positivity was found in 60%, 55%, and 32% of the cases, respectively. ER positivity with mean MC count of 23.55 was found in 36 cases, and 33 cases were positive for PR with a mean MC count of 24.18 and a significant P value. HER2 positive cases were 28 with a mean MC count of 20.82.

Conclusion: The presence of MCs in breast cancer is inversely proportional to the grade of tumor, i.e., a maximum number of MCs were seen in low grade tumors. In addition, there is a positive correlation between ER and PR receptor positivity with the presence of MCs in the stroma of breast cancer.},
}

@article {pmid32272928,
year = {2020},
author = {Sutham, K and Khuwuthyakorn, P and Thinnukool, O},
title = {Thailand medical mobile application for patients triage base on criteria based dispatch protocol.},
journal = {BMC medical informatics and decision making},
volume = {20},
number = {1},
pages = {66},
pmid = {32272928},
issn = {1472-6947},
abstract = {BACKGROUND: Before patients are admitted into the emergency department, it is important to undertake a pre-hospital process, both in terms of treatment performance and a request for resources from an emergency unit. The existing system to triage patients in Thailand is not functioning to its full capacity in either the primary medical system or pre-hospital treatment with shortcomings in the areas of speed, features, and appropriate systems. There is a high possibility of issuing a false Initial Dispatch Code (IDC), which will cause the over or underutilisation of emergency resources, such as rescue teams, community hospitals and emergency medical volunteers.

METHODS: A usability system design, together with a reliability test, was applied to develop an application to optimise the pre-hospital process, specifically to sort patients, using an IDC to improve the request for emergency resources. The triage mobile application was developed on both iOS and Android operating systems to support patient triage based on Criteria Based Dispatch (CBD). The 25 main symptom categories covered by CBD were used to design and develop the application, and 12 emergency medical staff, including doctors and nurses, were asked to test the system in the aspects of triage protocol correction, triage reliability, usability and user satisfaction.

RESULTS: The results of testing the proposed triage application were compared with the time used to triage by experienced staff and it was found that, in non-trauma cases, it was faster and more effective to use the application for emergency operations and to correct the IDC code representation.

CONCLUSIONS: The triage application will be utilised to support the pre-hospital process and to classify patients' conditions before they are admitted to the Emergency Department (ED). The application is suitable for users who are not medical emergency staff. Patients with non-trauma symptoms may be a suitable group to use the application in terms of time used to identify IDC for their own symptoms. The use of the application can be beneficial for those who wish to self-identify their symptoms before requesting medical services.},
}

@article {pmid32246378,
year = {2020},
author = {Le, AN and Harton, J and Desai, H and Powers, J and Zelley, K and Bradbury, AR and Nathanson, KL and Shah, PD and Doucette, A and Freedman, GM and Gabriel, P and Domchek, SM and MacFarland, SP and Maxwell, KN},
title = {Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome.},
journal = {Breast cancer research and treatment},
volume = {181},
number = {1},
pages = {181-188},
doi = {10.1007/s10549-020-05612-7},
pmid = {32246378},
issn = {1573-7217},
support = {K08CA21531//National Cancer Institute (US)/ ; ITMAT MHB//University of Pennsylvania/ ; 1017184//Burroughs Wellcome Fund/ ; },
abstract = {PURPOSE: Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy.

METHODS: A single-institution retrospective chart review was conducted for female breast cancer patients with confirmed germline TP53 mutation. The frequency of radiation-induced malignancies in LFS patients was compared to non-LFS breast cancer cases reported in the Penn Medicine Cancer Registry via statistical analyses.

RESULTS: We identified 51 female LFS breast cancer patients with 74 primary diagnoses. Fifty-seven% had a history of breast cancer only, and 25% had breast cancer as their presenting diagnosis of LFS. LFS-associated breast cancers were predominantly invasive ductal carcinoma (48%) and HER2+ (58%). Twenty patients underwent adjuvant radiotherapy with a median follow-up of 12.5 (2-20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer, and one (6%) patient developed sarcoma in the radiation field. This risk for radiation-induced malignancy associated with LFS was higher for both sarcoma and thyroid cancer in comparison with the control cohort.

CONCLUSIONS: We found a lower risk of radiation-induced secondary malignancies in LFS breast cancer patients than previously reported in the literature (33% risk of radiation-induced sarcoma). These findings suggest that LFS may not be an absolute contraindication for radiotherapy in breast cancer. The potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies in consideration of adjuvant radiotherapy for LFS breast cancer patients.},
}

@article {pmid32236595,
year = {2020},
author = {Gao, X and Bao, H and Liu, L and Zhu, W and Zhang, L and Yue, L},
title = {Systematic analysis of lysine acetylome and succinylome reveals the correlation between modification of H2A.X complexes and DNA damage response in breast cancer.},
journal = {Oncology reports},
volume = {43},
number = {6},
pages = {1819-1830},
doi = {10.3892/or.2020.7554},
pmid = {32236595},
issn = {1791-2431},
abstract = {Abnormal protein acetylation and succinylation in lysine residues can cause the initiation and development of numerous different types of tumors. However, to the best of our knowledge, there is currently a lack of systematic investigation in breast cancer. Using proteomic techniques, the present study systematically investigated the two modifications of all proteins in invasive ductal carcinoma tissues to identify potential targets. The results revealed significantly higher modification levels for the majority of proteins in breast cancer tissue when compared with para‑carcinomous normal tissue. The bioinformatic analysis demonstrated that either highly acetylated or succinylated proteins were significantly enriched in histone H2A.X (H2A.X) complexes and nucleophosmin (NPM1) may be the key member among them. The results of further analyses revealed that H2A.X complexes were associated with DNA damage response (DDR), and the proteomic results for protein quantification provided further evidence for the abnormal DDR condition in breast cancer tissues. Later, the western blotting results validated the high acetylation and succinylation levels of the majority of proteins, including the modification of NPM1 and its correlation with cell viability. Finally, the upregulation of H2A.X in breast cancer tissues further demonstrated the association between H2A.X complex modification and DDR in breast cancer. Overall, the present study systematically investigated the protein acetylation and succinylation in breast cancer and provided evidence to support H2A.X complexes as potential targets. These results broaden the horizon for breast cancer investigation and link it with epigenetics.},
}

@article {pmid32212794,
year = {2020},
author = {Rasmy, A and Sorour, Y},
title = {Effect of Obesity on Neoadjuvant Systemic Therapy Outcomes in Patients with Early Breast Cancer: A Retrospective Institutional Study.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {21},
number = {3},
pages = {683-691},
doi = {10.31557/APJCP.2020.21.3.683},
pmid = {32212794},
issn = {2476-762X},
mesh = {Adult ; Aged ; Body Mass Index ; Breast Neoplasms/complications/*therapy ; Female ; Humans ; Middle Aged ; *Neoadjuvant Therapy ; Obesity/*complications ; Retrospective Studies ; Treatment Outcome ; },
abstract = {BACKGROUND: Obesity and overweight are usually considered as poor prognostic factors in early breast cancer. Body mass index (BMI) is a significant predictive factor for lower pathologic complete response (pCR) rates after neo-adjuvant systemic therapy (NST). The relationship between obesity and breast cancer prognosis varies according to patient and tumor characteristics such as menopausal status and tumor subtype, respectively.

PATIENTS AND METHODS: Between March 2010 and October 2013, 80 patients with early breast cancer who had received standard NST from KFSH Saudi Arabia were included in this study. For statistical analysis, the study participants were categorized into two groups based on their BMI, as normal (BMI < 25 kg/m2) and obese groups (BMI ≥ 25 kg/m2). pCR was defined as non-invasive cancer in the breast/axillary tissue.

RESULTS: The median age of our patients was 48 (range, 38-68) years. Invasive ductal carcinoma (IDC) subtype was identified in 93.8% of the cases. Additionally, 26 (32.5%) and 33 (41.25%) patients were diagnosed with stage II and stage IIIA breast cancer, respectively. Lymphovascular invasion was detected in 32.5%, whereas intermediate and high-grade malignancy were found in 61.25% and 32.5% of the patients, respectively. Forty-four patients (55%) were obese. pCR was achieved in 56 patients (70%), and the comparison between patients with and without pCR revealed that those in the former group had significantly lower tumor grades. Significantly, lower relapse and mortality rates were distinguished in patients who achieved pCR than in those who did not. Additionally, comparison between normal and obese patients revealed that a high number of patients in both groups were post-menopausal (p = 0.001). However, survival analysis indicated the absence of significant differences in disease-free survival between the two groups based on BMI (p = 0.19). Conversely, patients with normal BMI had significantly better overall survival than obese patients (p = 0.029), with a higher mortality rate noted in the obese group (16.7% vs 2.3%, p = 0.037).

CONCLUSIONS: In the present study, 58.3% of patients that failed to achieve pCR had BMI above the normal level; they moreover had higher relapse rates and lower survival compared with normal BMI patients. This finding needs to be verified through further prospective studies to determine if BMI is a risk factor for breast cancer.},
}

Adult
Aged
Body Mass Index
Breast Neoplasms/complications/*therapy
Female
Humans
Middle Aged
*Neoadjuvant Therapy
Obesity/*complications
Retrospective Studies
Treatment Outcome

@article {pmid32190711,
year = {2020},
author = {Lee, RA and Vo, DT and Zurko, JC and Griffin, RL and Rodriguez, JM and Camins, BC},
title = {Infectious Diseases Consultation Is Associated With Decreased Mortality in Enterococcal Bloodstream Infections.},
journal = {Open forum infectious diseases},
volume = {7},
number = {3},
pages = {ofaa064},
pmid = {32190711},
issn = {2328-8957},
abstract = {Background: Enterococcus species frequently cause health care-associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown.

Methods: This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients >18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture.

Results: Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P < .001), echocardiography (79% vs 45%; P < .001), surgical intervention (20% vs 7%; P = 0.01), and have appropriate antibiotic duration (90% vs 46%; P < .001). Thirty-day mortality was significantly higher in the no-IDC group (27 % vs 12 %; P < .007). In multivariate analysis, 30-day in-hospital mortality was associated with both E. faecium bacteremia (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.09-5.23) and IDC (aOR, 0.35; 95% CI, 0.16-0.76).

Conclusions: Patients who received IDC for Enterococcus bacteremia had significantly lower 30-day mortality. Further prospective studies are necessary to determine if these outcomes can be validated in other institutions for patients who receive IDC with Enterococcus bacteremia.},
}

@article {pmid32161717,
year = {2020},
author = {Guo, T and Chen, Z and Xu, J and Zhang, Y},
title = {Change of Pathological Type to Metaplastic Squamous Cell Carcinoma of the Breast During Disease Recurrence: Case Report and Literature Review.},
journal = {Frontiers in oncology},
volume = {10},
number = {},
pages = {32},
pmid = {32161717},
issn = {2234-943X},
abstract = {Background: Metaplastic squamous cell carcinoma (SCC) of the breast is a rare and heterogeneous group of primary breast malignancies. The etiology, pathogenesis, and proper treatment for this kind rare breast cancer are still unclear. Case presentation: We reported a case of a 55-year-old woman with a palpable lump in the inner quadrant of the right breast. She underwent a right breast mass resection and sentinel lymph node biopsy, which revealed that the tumor was an invasive ductal carcinoma, followed by four cycles of doxorubicin plus cyclophosphamide and four cycles of docetaxel as adjuvant chemotherapy, and then simultaneous integrated boost intensity modulated radiotherapy to the whole right breast. After 2 years' follow-up, she had biopsy-proven disease recurrence in the right breast, which revealed SCC, and a mammogram showed abnormalities in the lower inner quadrant of the right breast and left axillary lymph nodes. Then we performed bilateral breast modified radical mastectomy, which confirmed that the recurrent tumors were metaplastic SCC, followed by adjuvant chemotherapy and adjuvant radiotherapy of the left supraclavicular and apical axillary regions. There has been no recurrent or metastatic evidence in the 16 months' follow-up since the second surgery. Conclusion: This case report shows that evolution of pathology type in recurrent breast cancer after initial treatment is possible. Detailed pathologic and immunohistochemical analyses are needed for identification of this change. Surgery and adjuvant radiation and chemotherapy are appropriate treatments for recurrent primary SCC of the breast.},
}

@article {pmid32157060,
year = {2019},
author = {Egawa, C and Yanai, A and Yanagawa, T and Takatsuka, Y and Takeno, A and Masuzawa, T and Hata, T and Kagawa, Y and Ohmura, Y and Katsura, Y and Murakami, K and Sakamoto, T and Kawai, K and Takeda, Y and Murata, K},
title = {[Long-Term Survival in a Case of Breast Cancer with Brain Metastases and No Other Distant Metastases Treated by Surgical Removal and Gamma Knife Radiosurgery].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {46},
number = {13},
pages = {2063-2065},
pmid = {32157060},
issn = {0385-0684},
mesh = {Adult ; *Brain Neoplasms/radiotherapy/secondary ; *Breast Neoplasms/radiotherapy ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; *Radiosurgery ; },
abstract = {A 44-year-oldwoman was diagnosedwith right breast cancer andund erwent mastectomy andaxillary lymph node dissection in February 2006. She was pathologically diagnosed with invasive ductal carcinoma without lymph node metastasis. Immunohistochemical examination showedthat the tumor was estrogen receptor positive, progesterone receptor negative, andhada HER2 status score of 0. She received 4 cycles of AC, followedby leuprorelin andtamoxifen. Several metastases were identified in the right supraclavicular lymph nodes in August 2008 during the endocrine therapy. Then, she received S-1 as the first-line chemotherapy. Although metastases showed complete response, she developed an eye disorder caused by S-1 and thus the treatment agent was changedto leuprorelin andanastrozole. She complainedof headache andright homonymous hemianopsia in November 2013. MRI showeda 42mm diameter tumor in the left occipital lobe, suspectedto be brain metastasis from breast cancer. Craniotomy was performedto remove the brain tumor, which was pathologically diagnosedas metastasis from breast cancer. In the brain tumor, the estrogen receptor status hadchangedto negative, but the HER2 status remained unchanged, showing a score of 0. Vinorelbine was administered after the brain surgery. Unfortunately, brain metastasis was foundin the dura mater near the surgical cavity, andgamma knife radiosurgery was performedin January 2014. Thereafter, brain metastases were repeatedly found, and gamma knife radiosurgery was again performed in January 2015, September 2016, and February 2017. In addition, a large tumor appearedin the left occipital lobe andwas surgically removed in June 2016. No other distant metastases were found, andvinorelbine was continueduntil February 2018. Because the patient developed dyslexia caused by gamma knife-induced radiation necrosis, bevacizumab was administered between November 2018 and April 2019. MRI showed that the edema due to radiation necrosis reduced and dyslexia symptoms improved. As of now, she has survivedfor 5 years and 6 months after the diagnosis of brain metastases.},
}

Adult
*Brain Neoplasms/radiotherapy/secondary
*Breast Neoplasms/radiotherapy
Female
Humans
Lymphatic Metastasis
Mastectomy
*Radiosurgery

@article {pmid32156965,
year = {2019},
author = {Kinoshita, H and Teraoka, H and Mori, T and Hasegawa, T and Noda, E and Takashima, T and Hirakawa, K and Ohira, M},
title = {[A Case of Breast Cancer Liver Metastases with Jaundice Responding to Chemotherapy].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {46},
number = {13},
pages = {2461-2463},
pmid = {32156965},
issn = {0385-0684},
mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; *Breast Neoplasms/drug therapy ; *Carcinoma, Ductal, Breast/drug therapy/secondary ; Female ; Humans ; *Jaundice/etiology ; *Liver Neoplasms/drug therapy/secondary ; Middle Aged ; Paclitaxel ; },
abstract = {A 50-year-old woman was referred to our hospital due to breast cancer with multiple liver metastasis diagnosed by CT scan. Laboratory findings showed liver dysfunction(T-Bil 7.6mg/dL)with marked elevation of tumor markers(CEA 727.9 ng/mL). Breast tumor biopsy showed an invasive ductal carcinoma(scirrhous type), ER(+), PgR(-), and HER2(3+). Combination therapy with docetaxel, carboplatin and, trastuzumab was administered after the end of 1 course of weekly paclitaxel plus bevacizumab regimen. The patient maintained a good condition without liver dysfunction 8 months after the first visit. Follow-up CT scan showed partial response of breast and hepatic tumors. Our case suggests that careful chemotherapy can improve the prognosis of breast cancer with liver metastasis even if a patient is in an icteric condition.},
}

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
*Breast Neoplasms/drug therapy
*Carcinoma, Ductal, Breast/drug therapy/secondary
Female
Humans
*Jaundice/etiology
*Liver Neoplasms/drug therapy/secondary
Middle Aged
Paclitaxel

@article {pmid32156942,
year = {2019},
author = {Morisaki, T and Takashima, T and Asano, Y and Kashiwagi, S and Noda, S and Onoda, N and Ohira, M},
title = {[Two Cases of Orbital Metastasis from Breast Cancer].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {46},
number = {13},
pages = {2392-2394},
pmid = {32156942},
issn = {0385-0684},
mesh = {Adult ; *Breast Neoplasms ; Eye Neoplasms/*secondary ; Female ; Humans ; *Liver Neoplasms ; Magnetic Resonance Imaging ; },
abstract = {Orbital metastasis from breast cancer is a rare condition. Here, we describe 2 cases of orbital metastasis from breast cancer. The first patient was a 26-year-old woman diagnosed with triple-negative invasive ductal carcinoma. She underwent surgery after neoadjuvant chemotherapy. One year after surgery, she had multiple bone metastases and then multiple liver metastases developed. During chemotherapy for metastatic disease, she complained ofheadaches and visual disturbances. Findings ofa MRI scan suggested a metastatic tumor in the left orbit. A total of 30 Gy of radiation therapy was administered, but she died a month after the orbital metastasis was discovered. The second patient was a 42-year-old woman, who had advanced breast cancer with bone metastasis. Diplopia developed 8 months after initiation of chemotherapy. Meningeal dissemination was suspected because ophthalmological examination revealed swelling ofbilateral optic discs. She lost her sight within a month. She died 2 months after the diagnosis oforbital metastasis. There was no evidence ofcentral nervous system metastasis in either case. Loss ofvision severely impairs patients' quality oflif e. It is important to know that there is rarely such a rapid progression ofdisease, especially in young patients with triple-negative disease.},
}

Adult
*Breast Neoplasms
Eye Neoplasms/*secondary
Female
Humans
*Liver Neoplasms
Magnetic Resonance Imaging

@article {pmid32156914,
year = {2019},
author = {Nakama, Y and Maruyama, Y and Hisaka, T and Yasumoto, M and Okabe, Y and Naito, Y and Yamaguchi, M and Tanaka, M and Tanaka, H and Akagi, Y and Okuda, K},
title = {[A Vesected Case of Pancreatic Metastasis from Breast Cancer Which Recurred Six Years after Breast Surgery].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {46},
number = {13},
pages = {2309-2311},
pmid = {32156914},
issn = {0385-0684},
mesh = {*Adenocarcinoma/secondary/surgery ; Adult ; *Breast Neoplasms/surgery ; Female ; Humans ; Mastectomy ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/secondary ; },
abstract = {A 43-year-old woman who underwent surgical resection of invasive ductal carcinoma in the left breast at the age of 37 years old presented at our hospital for evaluation of pancreatic tumor. The original tumor was estrogen receptor(ER)progesterone receptor(PgR)and HER2 positive. At that time, she underwent radical mastectomy with no evident nodal disease. Postoperatively, the patient was placed on adjuvant tamoxifen therapy for several years. Six years following the original diagnosis of breast cancer, she was referred to the hospital for routine check-up while asymptomatic. Follow-up examination showed a solitary hypodense mass approximately 0.9 cm in size in the pancreas body on dynamic CT scan. The patient underwent a standard distal pancreatectomy with standard regional lymphadenectomy. Histopathological examination and immunohistochemical features revealed that the tumor was compatible with metastatic pancreatic adenocarcinoma from breast cancer.},
}

*Adenocarcinoma/secondary/surgery
Adult
*Breast Neoplasms/surgery
Female
Humans
Mastectomy
Neoplasm Recurrence, Local
*Pancreatic Neoplasms/secondary

@article {pmid32138738,
year = {2020},
author = {Sun, T and Yang, W and Toprani, SM and Guo, W and He, L and DeLeo, AB and Ferrone, S and Zhang, G and Wang, E and Lin, Z and Hu, P and Wang, X},
title = {Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram.},
journal = {Cell communication and signaling : CCS},
volume = {18},
number = {1},
pages = {36},
doi = {10.1186/s12964-019-0507-3},
pmid = {32138738},
issn = {1478-811X},
support = {R01CA226981-01A1//Massachusetts General Hospital/ ; W81XWH-16-1-0500//U.S. Department of Defense/ ; },
abstract = {BACKGROUND: The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response.

METHODS: High aldehyde dehydrogenase activity (ALDH)bright and CD44+/CD24-/ESA+ cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA).

RESULTS: We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors.

CONCLUSION: DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.},
}

@article {pmid32119669,
year = {2020},
author = {Rangel, GW and Clark, MA and Kanjee, U and Goldberg, JM and MacInnis, B and José Menezes, M and Ferreira, MU and Duraisingh, MT},
title = {Plasmodium vivax transcriptional profiling of low input cryopreserved isolates through the intraerythrocytic development cycle.},
journal = {PLoS neglected tropical diseases},
volume = {14},
number = {3},
pages = {e0008104},
pmid = {32119669},
issn = {1935-2735},
support = {R01 AI140751/AI/NIAID NIH HHS/United States ; U19 AI089681/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 HL139337/HL/NHLBI NIH HHS/United States ; },
mesh = {Adolescent ; Child ; Child, Preschool ; Culture Media/chemistry ; Erythrocytes/*parasitology ; Female ; *Gene Expression Profiling ; *Host-Pathogen Interactions ; Humans ; Infant ; Infant, Newborn ; Malaria, Vivax/*parasitology ; Male ; Parasitology/methods ; Plasmodium vivax/genetics/*growth & development ; Sequence Analysis, RNA ; },
abstract = {Approximately one-third of the global population is at risk of Plasmodium vivax infection, and an estimated 7.51 million cases were reported in 2017. Although, P. vivax research is currently limited by the lack of a robust continuous in vitro culture system for this parasite, recent work optimizing short-term ex vivo culture of P. vivax from cryopreserved isolates has facilitated quantitative assays on synchronous parasites. Pairing this improved culture system with low-input Smart-seq2 RNAseq library preparation, we sought to determine whether transcriptional profiling of P. vivax would provide insight into the differential survival of parasites in different culture media. To this end we probed the transcriptional signature of three different ex vivo P. vivax samples in four different culture media using only 1000 cells for each time point taken during the course of the intraerythrocytic development cycle (IDC). Using this strategy, we achieved similar quality transcriptional data to previously reported P. vivax transcriptomes. We found little effect with varying culture media on parasite transcriptional signatures, identified many novel gametocyte-specific genes from transcriptomes of FACS-isolated gametocytes, and determined invasion ligand expression in schizonts in biological isolates and across the IDC. In total, these data demonstrate the feasibility and utility of P. vivax RNAseq-based transcriptomic studies using minimal biomass input to maximize experimental capacity.},
}

Adolescent
Child
Child, Preschool
Culture Media/chemistry
Erythrocytes/*parasitology
Female
*Gene Expression Profiling
*Host-Pathogen Interactions
Humans
Infant
Infant, Newborn
Malaria, Vivax/*parasitology
Male
Parasitology/methods
Plasmodium vivax/genetics/*growth & development
Sequence Analysis, RNA

@article {pmid32086991,
year = {2020},
author = {Luo, Y and Kishi, S and Sasaki, T and Ohmori, H and Fujiwara-Tani, R and Mori, S and Goto, K and Nishiguchi, Y and Mori, T and Kawahara, I and Kondoh, M and Kuniyasu, H},
title = {Targeting claudin-4 enhances chemosensitivity in breast cancer.},
journal = {Cancer science},
volume = {111},
number = {5},
pages = {1840-1850},
pmid = {32086991},
issn = {1349-7006},
support = {17KJB320010//Natural Science Foundation of Jiangsu Education Department Project/ ; 16H05164//Ministry of Education, Culture, Sports, Science and Technology/ ; 17K19923//Ministry of Education, Culture, Sports, Science and Technology/ ; 81702723//National Natural Science Foundation of China/ ; },
mesh = {Animals ; Antibodies/pharmacology/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Breast Neoplasms/*drug therapy/metabolism/pathology ; Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Claudin-1 ; Claudin-4/chemistry/genetics/*immunology ; Drug Synergism ; Female ; Humans ; MCF-7 Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Paclitaxel/pharmacology/therapeutic use ; Tamoxifen/pharmacology/therapeutic use ; Triple Negative Breast Neoplasms/drug therapy/metabolism/pathology ; Tumor Microenvironment/drug effects ; Xenograft Model Antitumor Assays ; },
abstract = {Triple negative breast cancer (TNBC) is characterized by highly aggressive phenotype, limited treatment options and a poor prognosis. In the present study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDC (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and was correlated with histological grade. In contrast, expression of CLDN4 was correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors and increased the intratumoral pH. Moreover, concurrent treatment with 4D3, PTX and tamoxifen, or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in a bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects.},
}

Animals
Antibodies/pharmacology/*therapeutic use
Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use
Breast Neoplasms/*drug therapy/metabolism/pathology
Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology
Cell Line, Tumor
Cell Proliferation/drug effects
Claudin-1
Claudin-4/chemistry/genetics/*immunology
Drug Synergism
Female
Humans
MCF-7 Cells
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Paclitaxel/pharmacology/therapeutic use
Tamoxifen/pharmacology/therapeutic use
Triple Negative Breast Neoplasms/drug therapy/metabolism/pathology
Tumor Microenvironment/drug effects
Xenograft Model Antitumor Assays

@article {pmid32029638,
year = {2020},
author = {Aminian, A and Zajichek, A and Arterburn, DE and Wolski, KE and Brethauer, SA and Schauer, PR and Nissen, SE and Kattan, MW},
title = {Predicting 10-Year Risk of End-Organ Complications of Type 2 Diabetes With and Without Metabolic Surgery: A Machine Learning Approach.},
journal = {Diabetes care},
volume = {43},
number = {4},
pages = {852-859},
doi = {10.2337/dc19-2057},
pmid = {32029638},
issn = {1935-5548},
abstract = {OBJECTIVE: To construct and internally validate prediction models to estimate the risk of long-term end-organ complications and mortality in patients with type 2 diabetes and obesity that can be used to inform treatment decisions for patients and practitioners who are considering metabolic surgery.

RESEARCH DESIGN AND METHODS: A total of 2,287 patients with type 2 diabetes who underwent metabolic surgery between 1998 and 2017 in the Cleveland Clinic Health System were propensity-matched 1:5 to 11,435 nonsurgical patients with BMI ≥30 kg/m2 and type 2 diabetes who received usual care with follow-up through December 2018. Multivariable time-to-event regression and random forest machine learning models were built and internally validated using fivefold cross-validation to predict the 10-year risk for four outcomes of interest. The prediction models were programmed to construct user-friendly web-based and smartphone applications of Individualized Diabetes Complications (IDC) Risk Scores for clinical use.

RESULTS: The prediction tools demonstrated the following discrimination ability based on the area under the receiver operating characteristic curve (1 = perfect discrimination and 0.5 = chance) at 10 years in the surgical and nonsurgical groups, respectively: all-cause mortality (0.79 and 0.81), coronary artery events (0.66 and 0.67), heart failure (0.73 and 0.75), and nephropathy (0.73 and 0.76). When a patient's data are entered into the IDC application, it estimates the individualized 10-year morbidity and mortality risks with and without undergoing metabolic surgery.

CONCLUSIONS: The IDC Risk Scores can provide personalized evidence-based risk information for patients with type 2 diabetes and obesity about future cardiovascular outcomes and mortality with and without metabolic surgery based on their current status of obesity, diabetes, and related cardiometabolic conditions.},
}

@article {pmid31992198,
year = {2020},
author = {Assefa, T and Zhang, J and Chowda-Reddy, RV and Moran Lauter, AN and Singh, A and O'Rourke, JA and Graham, MA and Singh, AK},
title = {Deconstructing the genetic architecture of iron deficiency chlorosis in soybean using genome-wide approaches.},
journal = {BMC plant biology},
volume = {20},
number = {1},
pages = {42},
pmid = {31992198},
issn = {1471-2229},
support = {NA//Iowa Soybean Association/ ; NA//Iowa State University/ ; NA//North Central Soybean Research Program (US)/ ; NA//Agricultural Research Service/ ; NA//National Institute of Food and Agriculture/ ; },
abstract = {BACKGROUND: Iron (Fe) is an essential micronutrient for plant growth and development. Iron deficiency chlorosis (IDC), caused by calcareous soils or high soil pH, can limit iron availability, negatively affecting soybean (Glycine max) yield. This study leverages genome-wide association study (GWAS) and a genome-wide epistatic study (GWES) with previous gene expression studies to identify regions of the soybean genome important in iron deficiency tolerance.

RESULTS: A GWAS and a GWES were performed using 460 diverse soybean PI lines from 27 countries, in field and hydroponic iron stress conditions, using more than 36,000 single nucleotide polymorphism (SNP) markers. Combining this approach with available RNA-sequencing data identified significant markers, genomic regions, and novel genes associated with or responding to iron deficiency. Sixty-nine genomic regions associated with IDC tolerance were identified across 19 chromosomes via the GWAS, including the major-effect quantitative trait locus (QTL) on chromosome Gm03. Cluster analysis of significant SNPs in this region deconstructed this historically prominent QTL into four distinct linkage blocks, enabling the identification of multiple candidate genes for iron chlorosis tolerance. The complementary GWES identified SNPs in this region interacting with nine other genomic regions, providing the first evidence of epistatic interactions impacting iron deficiency tolerance.

CONCLUSIONS: This study demonstrates that integrating cutting edge genome wide association (GWA), genome wide epistasis (GWE), and gene expression studies is a powerful strategy to identify novel iron tolerance QTL and candidate loci from diverse germplasm. Crops, unlike model species, have undergone selection for thousands of years, constraining and/or enhancing stress responses. Leveraging genomics-enabled approaches to study these adaptations is essential for future crop improvement.},
}

@article {pmid31902979,
year = {2019},
author = {Sultan, G and Zubair, S and Tayubi, IA and Dahms, HU and Madar, IH},
title = {Towards the early detection of ductal carcinoma (a common type of breast cancer) using biomarkers linked to the PPAR(γ) signaling pathway.},
journal = {Bioinformation},
volume = {15},
number = {11},
pages = {799-805},
pmid = {31902979},
issn = {0973-2063},
abstract = {Breast cancer is a leading cause of morbidity and mortality among women comprising about 12% females worldwide. The underlying alteration in the gene expression, molecular mechanism and metabolic pathways responsible for incidence and progression of breast tumorigenesis are yet not completely understood. In the present study, potential biomarker genes involved in the early progression for early diagnosis of breast cancer has been detailed. Regulation and Gene profiling of Ductal Carcinoma In-situ (DCIS), Invasive Ductal Carcinoma (IDC) and healthy samples have been analyzed to follow their expression pattern employing normalization, statistical calculation, DEGs annotation and Protein-Protein Interaction (PPI) network. We have performed a comparative study on differentially expressed genes among Healthy vs DCIS, Healthy vsIDC and DCIS vs IDC. We found MCM102 and SLC12A8as consistently over-expressed and LEP, SORBS1, SFRP1, PLIN1, FABP4, RBP4, CD300LG, ID4, CRYAB, ECRG4, G0S2, FMO2, ADAMTS5, CAV1, CAV2, ABCA8, MAMDC2, IGFBP6, CLDN11, TGFBR3as under-expressed genes in all the 3 conditions categorized for pre-invasive and invasive ductal breast carcinoma. These genes were further studied for the active pathways where PPAR(γ) signaling pathway was found to be significantly involved. The gene expression profile database can be a potential tool in the early diagnosis of breast cancer.},
}

@article {pmid31876826,
year = {2020},
author = {Phan Sy, O and Rouchy, RC and De Leiris, N and Nika, E and Djaileb, L},
title = {FDG PET/CT of a Supraclavicular Silicone Granuloma at Follow-up of a Breast Carcinoma.},
journal = {Clinical nuclear medicine},
volume = {45},
number = {3},
pages = {e169-e170},
doi = {10.1097/RLU.0000000000002894},
pmid = {31876826},
issn = {1536-0229},
mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/complications/*surgery ; Female ; *Fluorodeoxyglucose F18 ; Follow-Up Studies ; Granuloma/*diagnostic imaging/*etiology/pathology ; Humans ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Silicones/*adverse effects ; },
abstract = {We report herein the case of a 33-year-old woman who was referred for FDG PET/CT staging prior to pregnancy after a 4-year lost to follow-up for a breast invasive ductal carcinoma (pT2N1 SBRII). FDG PET/CT revealed right supraclavicular lymphadenopathy potentially caused by breast carcinoma recurrence. No additional site was involved. Supraclavicular ultrasonography showed typical "snowstorm" appearance. MRI revealed signs of breast implant intracapsular rupture and signal intensity of silicone within a supraclavicular node. Fine-needle aspiration and microbiopsy of adenopathy finally confirmed silicone granuloma and ruled out breast cancer recurrence.},
}

Adult
Aged
Biopsy, Fine-Needle
Breast Neoplasms/complications/*surgery
Female
*Fluorodeoxyglucose F18
Follow-Up Studies
Granuloma/*diagnostic imaging/*etiology/pathology
Humans
Middle Aged
*Positron Emission Tomography Computed Tomography
Silicones/*adverse effects

@article {pmid31856858,
year = {2019},
author = {Wan, L and Liu, T and Hong, Z and Pan, Y and Sizemore, ST and Zhang, J and Ma, Z},
title = {NEDD4 expression is associated with breast cancer progression and is predictive of a poor prognosis.},
journal = {Breast cancer research : BCR},
volume = {21},
number = {1},
pages = {148},
pmid = {31856858},
issn = {1465-542X},
mesh = {Adult ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Cell Line, Tumor ; Disease Progression ; Female ; *Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Nedd4 Ubiquitin Protein Ligases/*genetics/metabolism ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Receptor, IGF Type 1/metabolism ; Young Adult ; },
abstract = {BACKGROUND: A role for neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) in tumorigenesis has been suggested. However, information is lacking on its role in breast tumor biology. The purpose of this study was to determine the role of NEDD4 in the promotion of the growth and progression of breast cancer (BC) and to evaluate the clinicopathologic and prognostic significance of NEDD4.

METHODS: The impact of NEDD4 expression in BC cell growth was determined by Cell Counting Kit-8 and colony formation assays. Formalin-fixed paraffin-embedded specimens were collected from 133 adjacent normal tissues (ANTs), 445 BC cases composed of pre-invasive ductal carcinoma in situ (DCIS, n = 37), invasive ductal carcinomas (IDC, n = 408, 226 without and 182 with lymph node metastasis), and 116 invaded lymph nodes. The expression of NEDD4 was analyzed by immunohistochemistry. The association between NEDD4 expression and clinicopathological characteristics was analyzed by chi-square test. Survival was evaluated using the Kaplan-Meier method, and curves were compared using a log-rank test. Univariate and multivariate analyses were performed using the Cox regression method.

RESULTS: NEDD4 promoted BC growth in vitro. In clinical retrospective studies, 16.5% of ANTs (22/133) demonstrated positive NEDD4 staining. Strikingly, the proportion of cases showing NEDD4-positive staining increased to 51.4% (19/37) in DCIS, 58.4% (132/226) in IDC without lymph node metastasis, and 73.1% (133/182) in BC with lymph node metastasis (BCLNM). In addition, NEDD4-positive staining was associated with clinical parameters, including tumor size (P = 0.030), nodal status (P = 0.001), estrogen receptor status (P = 0.035), and progesterone receptor status (P = 0.023). Moreover, subset analysis in BCLNM revealed that high NEDD4 expression correlated with an elevated risk of relapse (P = 0.0276). Further, NEDD4 expression was an independent prognostic predictor. Lastly, the rates for 10-year overall survival and disease-free survival were significantly lower in patients with positive NEDD4 staining than those in BC patients with negative NEDD4 staining BC (P = 0.0024 and P = 0.0011, respectively).

CONCLUSIONS: NEDD4 expression is elevated in BC and is associated with BC growth. NEDD4 correlated with clinicopathological parameters and predicts a poor prognosis. Thus, NEDD4 is a potential biomarker of poor prognosis and a potential therapeutic target for BC treatment.},
}

Adult
Biomarkers, Tumor
Breast Neoplasms/*genetics/*mortality/pathology
Cell Line, Tumor
Disease Progression
Female
*Gene Expression
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Middle Aged
Nedd4 Ubiquitin Protein Ligases/*genetics/metabolism
Neoplasm Grading
Neoplasm Staging
Prognosis
Proportional Hazards Models
Proto-Oncogene Proteins c-akt/metabolism
RNA Interference
Receptor, IGF Type 1/metabolism
Young Adult

@article {pmid31856344,
year = {2020},
author = {Giles, M and Graham, L and Ball, J and King, J and Watts, W and Harris, A and Oldmeadow, C and Ling, R and Paul, M and O'Brien, A and Parker, V and Wiggers, J and Foureur, M},
title = {Implementation of a multifaceted nurse-led intervention to reduce indwelling urinary catheter use in four Australian hospitals: A pre- and postintervention study.},
journal = {Journal of clinical nursing},
volume = {29},
number = {5-6},
pages = {872-886},
doi = {10.1111/jocn.15142},
pmid = {31856344},
issn = {1365-2702},
support = {//NSW Ministry of Health Translational Research Grants Scheme/ ; },
mesh = {Adult ; Catheter-Related Infections/etiology/*prevention & control ; Catheters, Indwelling/*adverse effects ; Controlled Before-After Studies ; Female ; Humans ; Male ; New South Wales ; Patient Care Bundles/*nursing ; Practice Patterns, Nurses' ; Urinary Catheters/*adverse effects ; Urinary Tract Infections/etiology/*prevention & control ; },
abstract = {AIMS AND OBJECTIVES: This study aimed to reduce indwelling urinary catheter (IDC) use and duration through implementation of a multifaceted "bundled" care intervention.

BACKGROUND: Indwelling urinary catheters present a risk for patients through the potential development of catheter-associated urinary tract infection (CAUTI), with duration of IDC a key risk factor. Catheter-associated urinary tract infection is considered preventable yet accounts for over a third of all hospital-acquired infections. The most effective CAUTI reduction strategy is to avoid IDC use where ever possible and to remove the IDC as early as appropriate.

DESIGN: A cluster-controlled pre- and poststudy at a facility level with a phased intervention implementation approach.

METHODS: A multifaceted intervention involving a "No CAUTI" catheter care bundle was implemented, in 4 acute-care hospitals, 2 in metropolitan and 2 in rural locations, in New South Wales, Australia. Indwelling urinary catheter point prevalence and duration data were collected at the bedside on 1,630 adult inpatients at preintervention and 1,677 and 1,551 at 4 and 9 months postintervention. This study is presented in line with the StaRI checklist (see Appendix S1).

RESULTS: A nonsignificant trend towards reduction in IDC prevalence was identified, from 12% preintervention to 10% of all inpatients at 4 and 9 months. Variability in preintervention IDC prevalence existed across hospitals (8%-16%). Variability in reduction was evident across hospitals at 4 months (between -2% and 4%) and 9 months (between 0%-8%). Hospitals with higher preintervention prevalence showed larger decreases, up to 50% when preintervention prevalence was 16%. Indwelling urinary catheter duration increased as more of the short-term IDC placements were avoided.

CONCLUSIONS: Implementation of a multifaceted intervention resulted in reduced IDC use in four acute-care hospitals in Australia. This result was not statistically significant but did reflect a positive trend of reduction. There was a significant reduction in short-term IDC use at 9 months postintervention.

Clinical nurse leaders can effectively implement change strategies that influence patient outcomes. Implementation of the evidence-based "No CAUTI" bundle increased awareness of appropriate indications and provided nurses with the tools to inform decision-making related to insertion and removal of IDCs in acute inpatient settings. Working in partnership with inpatients and the multidisciplinary team is essential in minimising acute-care IDC use.},
}

Adult
Catheter-Related Infections/etiology/*prevention & control
Catheters, Indwelling/*adverse effects
Controlled Before-After Studies
Female
Humans
Male
New South Wales
Patient Care Bundles/*nursing
Practice Patterns, Nurses'
Urinary Catheters/*adverse effects
Urinary Tract Infections/etiology/*prevention & control

@article {pmid31856180,
year = {2019},
author = {Walzer, KA and Fradin, H and Emerson, LY and Corcoran, DL and Chi, JT},
title = {Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging.},
journal = {PLoS genetics},
volume = {15},
number = {12},
pages = {e1008506},
pmid = {31856180},
issn = {1553-7404},
mesh = {Gene Expression Profiling ; Gene Expression Regulation, Developmental ; In Situ Hybridization, Fluorescence/*methods ; Life Cycle Stages ; Microfluidic Analytical Techniques ; Multigene Family ; Plasmodium falciparum/genetics/*growth & development ; Protozoan Proteins/*genetics ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; },
abstract = {Malaria parasites follow a complex life cycle that consists of multiple stages that span from the human host to the mosquito vector. Among the species causing malaria, Plasmodium falciparum is the most lethal, with clinical symptoms manifesting during the intraerythrocytic developmental cycle (IDC). During the IDC, P. falciparum progresses through a synchronous and continuous cascade of transcriptional programming previously established using population analyses. While individual parasites are known to exhibit transcriptional variations to evade the host immune system or commit to a sexual fate, such rare expression heterogeneity is largely undetectable on a population level. Therefore, we combined single-cell RNA-sequencing (scRNA-seq) on a microfluidic platform and fluorescence imaging to delineate the transcriptional variations among individual parasites during late asexual and sexual stages. The comparison between asexual and sexual parasites uncovered a set of previously undefined sex-specific genes. Asexual parasites were segregated into three distinct clusters based on the differential expression of genes encoding SERAs, rhoptry proteins, and EXP2 plus transporters. Multiple pseudotime analyses revealed that these stage-specific transitions are distinct. RNA fluorescent in situ hybridization of cluster-specific genes validated distinct stage-specific expression and transitions during the IDC and defined the highly variable transcriptional pattern of EXP2. Additionally, these analyses indicated huge variations in the stage-specific transcript levels among parasites. Overall, scRNA-seq and RNA-FISH of P. falciparum revealed distinct stage transitions and unexpected degrees of heterogeneity with potential impact on transcriptional regulation during the IDC and adaptive responses to the host.},
}

Gene Expression Profiling
Gene Expression Regulation, Developmental
In Situ Hybridization, Fluorescence/*methods
Life Cycle Stages
Microfluidic Analytical Techniques
Multigene Family
Plasmodium falciparum/genetics/*growth & development
Protozoan Proteins/*genetics
Sequence Analysis, RNA/*methods
Single-Cell Analysis/*methods

@article {pmid31849088,
year = {2020},
author = {Arispe Angulo, KR and Jawa, Z and Visotcky, A and Majidi, SS and Chitambar, CR and Jorns, JM},
title = {A high mitotic score in breast cancer after neoadjuvant chemotherapy is predictive of outcome and associated with a distinct morphology.},
journal = {Histopathology},
volume = {76},
number = {5},
pages = {661-670},
doi = {10.1111/his.14049},
pmid = {31849088},
issn = {1365-2559},
abstract = {AIMS: Neoadjuvant chemotherapy (NAC) is frequently used for the treatment of breast cancer. We sought to analyse the clinical, morphological and immunohistochemical features of tumours from patients who did not achieve pathological complete response following NAC.

METHODS AND RESULTS: We identified stage I-III post-NAC breast cancers from surgical resections (2000-2016) with evaluable residual invasive carcinoma [ypT1a(m) or greater and ≥15% tumour cellularity]. One hundred and forty-three tumours from 142 patients were included. On univariable analysis, a high (score 3) post-NAC mitotic score (as compared with 1 or 2) was significantly associated with invasive ductal carcinoma (IDC) subtype (P = 0.023), high grade, pushing borders with zones of necrosis, hormone receptor and triple-negative status, lack of hormonal therapy, higher cellularity (P < 0.001), and a higher percentage of tumour-infiltrating lymphocytes (P = 0.016). Multivariable analysis showed a high post-NAC mitotic score to be significantly associated with recurrence, distant metastasis, and shortened survival (hazard ratios of 5.73, 4.49, and 3.68, respectively). High post-NAC mitotic score tumours (n = 32) were IDC and had a high Ki67 proliferation index (median, 55%). Of these, 24 (75%) had pushing borders with zones of necrosis; 19 (79.2%) of these had necrosis on preoperative imaging, and 24 (75%), 15 (46.9%) and four (12.5%) lacked androgen receptor, GATA-3 and cytokeratin 18 expression, respectively.

CONCLUSIONS: High post-NAC mitotic score breast cancers cause high morbidity and mortality, frequently have pushing borders and zones of necrosis, and may show loss of common 'breast cancer markers'. Our findings support that necrosis in pretreatment studies and post-NAC mitotic score should be routinely reported, as they offer significant additional prognostic information to guide management.},
}

@article {pmid31844635,
year = {2019},
author = {Redell, M and Sierra-Hoffman, M and Assi, M and Bochan, M and Chansolme, D and Gandhi, A and Sheridan, K and Soosaipillai, I and Walsh, T and Massey, J},
title = {The CHROME Study, a Real-world Experience of Single- and Multiple-Dose Oritavancin for Treatment of Gram-Positive Infections.},
journal = {Open forum infectious diseases},
volume = {6},
number = {11},
pages = {ofz479},
pmid = {31844635},
issn = {2328-8957},
abstract = {Background: Oritavancin (ORI) is a long-acting lipoglycopeptide indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible Gram-positive (GP) pathogens.

Methods: Data collected from a retrospective observational program (2014-2017), Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME), describe the utilization, outcomes, and adverse events (AEs) associated with ORI in 440 patients treated at 26 US sites for ABSSSI and other GP infections.

Results: Clinical success in evaluable patients receiving at least 1 dose of oritavancin was 88.1% (386/438). In a subgroup of patients who received ORI for skin and soft tissue infections (n = 401) and bacteremia (n = 7), clinical success was achieved in 89.0% and 100%, respectively. A cohort of 32 patients received 2-10 ORI doses separated by no more than 14 days for complicated GP infections. Clinical success was observed in 30 of 32 patients (93.8%), including 10 of 11 (90.9%) patients with bone and joint infections and 7 of 8 (87.5%) patients with osteomyelitis. In the safety evaluable population, the overall rate of AEs was 6.6%.

Conclusions: We describe results from a real-world program that includes the largest multicenter, retrospective, observational study in patients who received at least 1 dose of ORI for the treatment of GP infections. This study confirms that ORI is an effective, well-tolerated antibiotic used in single and multiple doses for the treatment of ABSSSIs and complicated GP infections.},
}

@article {pmid31844357,
year = {2019},
author = {Amadi, OF and Okeke, IB and Ndu, IK and Ekwochi, U and Nduagubam, OC and Ezenwosu, OU and Asinobi, IN and Osuorah, CD},
title = {Cancer Mortality in the Niger Delta Region of Nigeria: A Case Study of the University of Port Harcourt Teaching Hospital.},
journal = {Nigerian medical journal : journal of the Nigeria Medical Association},
volume = {60},
number = {5},
pages = {262-267},
pmid = {31844357},
issn = {0300-1652},
abstract = {Aim: The aim of this study is to determine the pattern of cancer mortality (CM) seen in the University of Port Harcourt Teaching Hospital (UPTH) which is a cancer reference center in the Niger Delta Region.

Methodology: This is a 6-year retrospective study of cancer-related deaths in UPTH using patients' admission registers in all the wards and emergency units. Furthermore, the death certificates of cases were reviewed.

Results: Three hundred and sixteen cases of cancer-related deaths occurred, involving 174 females and 142 males, in a female-to-male sex ratio of 1.2:1. All age groups were affected, with age group 40-49 years accounting for the majority (20.6%). CM was seen in all the systems, except the central nervous system. Cancers of the gastrointestinal tract and its accessory organs (liver and gall bladder) caused most mortality (27.9%), in a female-to-male ratio of 0.8:1. The single most involved organ in CM is the female breast (20.6%), distantly followed by mortality due to prostate cancers and hematolymphoid cancers which accounted for 9.2% each. Colorectal cancers accounted for 7.3% of cancer deaths and ranked 4th. Cancers of both cervix and stomach each accounted for 5.7% of mortality. The major histologic diagnoses were carcinomas (adenocarcinoma; 36.7%, invasive ductal carcinoma; 20.3%, squamous cell carcinomas; 8.2% and hepatocellular carcinomas; 4.4%). Leukemias and lymphomas accounted for 9.2% of cases, whereas sarcomas accounted for 5.1% of cases.

Conclusion: Infection-related and noninfection-related cancers cause most mortality in UPTH. The 5th decade was the most commonly affected, while female breast was the single most involved organ. Breast, prostate and hematolymphoid malignancies are common causes of CM with death from breast occurring earliest. Majority of the deceased were educated, working-class urban dwellers. More advocacies on public acceptance of cancer screening and cancer preventive lifestyles as well as governments' improvement on workforce training and treatment infrastructure will improve the current CM profile in Port Harcourt.},
}

@article {pmid31809502,
year = {2019},
author = {Pick, FC and Fish, KE and Biggs, CA and Moses, JP and Moore, G and Boxall, JB},
title = {Application of enhanced assimilable organic carbon method across operational drinking water systems.},
journal = {PloS one},
volume = {14},
number = {12},
pages = {e0225477},
pmid = {31809502},
issn = {1932-6203},
mesh = {Carbon/*analysis/metabolism ; Drinking Water/chemistry/microbiology/*standards ; Flow Cytometry/methods ; Organic Chemicals/*analysis/metabolism ; Pseudomonas fluorescens/metabolism ; Reproducibility of Results ; Spirillum/metabolism ; Water Microbiology/*standards ; Water Purification ; Water Quality/*standards ; },
abstract = {Assimilable organic carbon (AOC) is known to correlate with microbial growth, which can consequently degrade drinking water quality. Despite this, there is no standardised AOC test that can be applied to drinking water distribution systems (DWDS). Herein we report the development of a quick, robust AOC that incorporates known strains Pseudomonas fluorescens strain P-17 and Spirillum strain NOX, a higher inoculum volume and enumeration using flow cytometry to generate a quicker (total test time reduced from 14 to 8 days), robust method. We apply the developed AOC test to twenty drinking water treatment works (WTW) to validate the method reproducibility and resolution across a wide range of AOC concentrations. Subsequently, AOC was quantified at 32 sample points, over four DWDS, for a year in order to identify sinks and sources of AOC in operative networks. Application of the developed AOC protocol provided a previously unavailable insight and novel evidence of pipes and service reservoirs exhibiting different AOC and regrowth behaviour. Observed correlations between AOC and microbial growth highlight the importance of monitoring AOC as an integral part of managing drinking water quality at the consumers tap.},
}

Carbon/*analysis/metabolism
Drinking Water/chemistry/microbiology/*standards
Flow Cytometry/methods
Organic Chemicals/*analysis/metabolism
Pseudomonas fluorescens/metabolism
Reproducibility of Results
Spirillum/metabolism
Water Microbiology/*standards
Water Purification
Water Quality/*standards

@article {pmid31791269,
year = {2019},
author = {Lee, CH and Hsieh, JC and Wu, TM and Yeh, TS and Wang, HM and Lin, YC and Chen, JS and Lee, CL and Huang, WK and Hung, TM and Yen, TT and Chan, SC and Chou, WC and Kuan, FC and Hu, CC and Chang, PH},
title = {Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.},
journal = {BMC cancer},
volume = {19},
number = {1},
pages = {1167},
pmid = {31791269},
issn = {1471-2407},
support = {CMRPG2D0171, CMRPG2D0172, CMRPG2G0681, CMRPG2G0682//Chang Gung Memorial Hospital/ ; CMRPG2D0173//Chang Gung Memorial Hospital/ ; PMRPG3G0791, CMRPG3G0771, CORPG3F0731, CMRPG3E1631-33//Chang Gung Memorial Hospital/ ; CMRPG3G1131-1133, CMRPG3H0871-73//Chang Gung Memorial Hospital/ ; MOST-108-2628-B-182A-001//Ministry of Science and Technology, Taiwan/ ; MOST-107-2314-B-182-053, MOST-104-2314-B-182-031-MY3//Ministry of Science and Technology, Taiwan/ ; },
mesh = {AC133 Antigen/immunology ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/drug therapy/*mortality/pathology ; Carcinoma, Ductal, Breast/drug therapy/*mortality/pathology ; Cell Count ; Female ; Humans ; Liquid Biopsy ; Middle Aged ; Neoplastic Cells, Circulating/immunology/*pathology ; Neoplastic Stem Cells/immunology/*pathology ; Prognosis ; Prospective Studies ; Survival Analysis ; Treatment Outcome ; },
abstract = {BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy.

METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45- cells and cCSCs as CD133+EpCAM+Hoechst+CD45- cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses.

RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS.

CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.},
}

AC133 Antigen/immunology
Adult
Aged
Aged, 80 and over
Breast Neoplasms/drug therapy/*mortality/pathology
Carcinoma, Ductal, Breast/drug therapy/*mortality/pathology
Cell Count
Female
Humans
Liquid Biopsy
Middle Aged
Neoplastic Cells, Circulating/immunology/*pathology
Neoplastic Stem Cells/immunology/*pathology
Prognosis
Prospective Studies
Survival Analysis
Treatment Outcome

@article {pmid31779581,
year = {2019},
author = {Luo, K and Wang, S and Fu, Y and Zhou, P and Huang, X and Gu, Q and Li, W and Wang, Y and Hu, F and Liu, S},
title = {Rapid genomic DNA variation in newly hybridized carp lineages derived from Cyprinus carpio (♀) × Megalobrama amblycephala (♂).},
journal = {BMC genetics},
volume = {20},
number = {1},
pages = {87},
pmid = {31779581},
issn = {1471-2156},
mesh = {Animals ; Carps/genetics/*physiology ; Evolution, Molecular ; Female ; Fish Proteins/genetics ; *Genetic Variation ; Goldfish/genetics/*physiology ; Homeodomain Proteins/*genetics ; Hybridization, Genetic ; Male ; Multigene Family ; Sequence Analysis, DNA/veterinary ; },
abstract = {BACKGROUND: Distant hybridization can generate changes in phenotypes and genotypes that lead to the formation of new hybrid lineages with genetic variation. In this study, the establishment of two bisexual fertile carp lineages, including the improved diploid common carp (IDC) lineage and the improved diploid scattered mirror carp (IDMC) lineage, from the interspecific hybridization of common carp (Cyprinus carpio, 2n = 100) (♀) × blunt snout bream (Megalobrama amblycephala, 2n = 48) (♂), provided a good platform to investigate the genetic relationship between the parents and their hybrid progenies.

RESULT: In this study, we investigated the genetic variation of 12 Hox genes in the two types of improved carp lineages derived from common carp (♀) × blunt snout bream (♂). Hox gene clusters were abundant in the first generation of IDC, but most were not stably inherited in the second generation. In contrast, we did not find obvious mutations in Hox genes in the first generation of IDMC, and almost all the Hox gene clusters were stably inherited from the first generation to the second generation of IDMC. Interestingly, we found obvious recombinant clusters of Hox genes in both improved carp lineages, and partially recombinant clusters of Hox genes were stably inherited from the first generation to the second generation in both types of improved carp lineages. On the other hand, some Hox genes were gradually becoming pseudogenes, and some genes were completely pseudogenised in IDC or IDMC.

CONCLUSIONS: Our results provided important evidence that distant hybridization produces rapid genomic DNA changes that may or may not be stably inherited, providing novel insights into the function of hybridization in the establishment of improved lineages used as new fish resources for aquaculture.},
}

Animals
Carps/genetics/*physiology
Evolution, Molecular
Female
Fish Proteins/genetics
*Genetic Variation
Goldfish/genetics/*physiology
Homeodomain Proteins/*genetics
Hybridization, Genetic
Male
Multigene Family
Sequence Analysis, DNA/veterinary

@article {pmid31744918,
year = {2019},
author = {Xie, M and Leroy, H and Mascarau, R and Woottum, M and Dupont, M and Ciccone, C and Schmitt, A and Raynaud-Messina, B and Vérollet, C and Bouchet, J and Bracq, L and Benichou, S},
title = {Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction.},
journal = {mBio},
volume = {10},
number = {6},
pages = {},
pmid = {31744918},
issn = {2150-7511},
mesh = {CD4-Positive T-Lymphocytes/metabolism/virology ; Dendritic Cells/metabolism/virology ; HIV Infections/*metabolism/*virology ; HIV-1/*physiology ; Humans ; Macrophages/metabolism/virology ; Myeloid Cells/metabolism/virology ; SAM Domain and HD Domain-Containing Protein 1/*metabolism ; *Viral Tropism ; *Virus Replication ; },
abstract = {Dendritic cells (DCs) and macrophages as well as osteoclasts (OCs) are emerging as target cells of HIV-1 involved in virus transmission, dissemination, and establishment of persistent tissue virus reservoirs. While these myeloid cells are poorly infected by cell-free viruses because of the high expression levels of cellular restriction factors such as SAMHD1, we show here that HIV-1 uses a specific and common cell-to-cell fusion mechanism for virus transfer and dissemination from infected T lymphocytes to the target cells of the myeloid lineage, including immature DCs (iDCs), OCs, and macrophages, but not monocytes and mature DCs. The establishment of contacts with infected T cells leads to heterotypic cell fusion for the fast and massive transfer of viral material into OC and iDC targets, which subsequently triggers homotypic fusion with noninfected neighboring OCs and iDCs for virus dissemination. These two cell-to-cell fusion processes are not restricted by SAMHD1 and allow very efficient spreading of virus in myeloid cells, resulting in the formation of highly virus-productive multinucleated giant cells. These results reveal the cellular mechanism for SAMHD1-independent cell-to-cell spreading of HIV-1 in myeloid cell targets through the formation of the infected multinucleated giant cells observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients.IMPORTANCE We demonstrate that HIV-1 uses a common two-step cell-to-cell fusion mechanism for massive virus transfer from infected T lymphocytes and dissemination to myeloid target cells, including dendritic cells and macrophages as well as osteoclasts. This cell-to-cell infection process bypasses the restriction imposed by the SAMHD1 host cell restriction factor for HIV-1 replication, leading to the formation of highly virus-productive multinucleated giant cells as observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients. Since myeloid cells are emerging as important target cells of HIV-1, these results contribute to a better understanding of the role of these myeloid cells in pathogenesis, including cell-associated virus sexual transmission, cell-to-cell virus spreading, and establishment of long-lived viral tissue reservoirs.},
}

CD4-Positive T-Lymphocytes/metabolism/virology
Dendritic Cells/metabolism/virology
HIV Infections/*metabolism/*virology
HIV-1/*physiology
Humans
Macrophages/metabolism/virology
Myeloid Cells/metabolism/virology
SAM Domain and HD Domain-Containing Protein 1/*metabolism
*Viral Tropism
*Virus Replication

@article {pmid31737920,
year = {2020},
author = {Taylor, AS and Morgan, TM and Wallington, DG and Chinnaiyan, AM and Spratt, DE and Mehra, R},
title = {Correlation between cribriform/intraductal prostatic adenocarcinoma and percent Gleason pattern 4 to a 22-gene genomic classifier.},
journal = {The Prostate},
volume = {80},
number = {2},
pages = {146-152},
doi = {10.1002/pros.23926},
pmid = {31737920},
issn = {1097-0045},
mesh = {Adenocarcinoma/*genetics/*pathology ; Aged ; Biomarkers, Tumor/genetics ; Carcinoma, Ductal/*genetics/*pathology ; Cell Growth Processes/genetics ; Cohort Studies ; Genetic Predisposition to Disease ; Genomics/methods ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/*pathology ; RNA, Neoplasm/*genetics ; },
abstract = {BACKGROUND: The Decipher test measures expression of 22 RNA biomarkers associated with aggressive prostate cancer used to improve risk stratification of patients to help guide management. To date, Decipher's genomic classification has not been extensively correlated with specific histologic growth patterns in prostatic adenocarcinoma. With a growing understanding of the clinical aggressiveness associated with cribriform growth pattern (CF), intraductal carcinoma (IDC), and percent Gleason pattern 4 (G4%), we sought to determine if their presence was associated with an increased genomic risk as measured by the Decipher assay.

DESIGN: Clinical use of the Decipher assay was performed on the highest Gleason score (GS) tumor nodule of prostatectomy specimens from a prospective cohort of 48 patients, with GS varying from 7 through 9 to help guide clinical risk stratification. The tumors were reviewed for CF, IDC, and G4%, which were then compared to the Decipher score (0-1) and risk stratification (high vs not high).

RESULTS: The presence of CF/IDC was significantly associated with Decipher risk score (P = .007), with a high-risk Decipher score in 22% vs 56% of patients without or with CF/IDC. On binary logistic regression analysis, G4% (odds ratio [OR] 1.04 per percent increase [95% confidence interval [CI], 1.02-1.06]; P = .0004) and CF predominant (OR, 9.60 [95%CI, 1.48-62.16]; P = .02) were significantly associated with a high-risk GC score. IDC did not reach significance (OR, 1.92 [95%CI, 0.65-5.67]; P = .24).

CONCLUSIONS: Our findings add to an expanding knowledge base that supports G4% and CF/IDC as molecularly unique and clinically relevant features in prostatic adenocarcinoma. These histologic features should be standardly reported as they are associated with more aggressive prostate cancer. Future work should determine the independent information of these histologic findings that are relative to genomic assessment on long-term outcomes.},
}

Adenocarcinoma/*genetics/*pathology
Aged
Biomarkers, Tumor/genetics
Carcinoma, Ductal/*genetics/*pathology
Cell Growth Processes/genetics
Cohort Studies
Genetic Predisposition to Disease
Genomics/methods
Humans
Male
Middle Aged
Neoplasm Grading
Prostatic Neoplasms/*genetics/*pathology
RNA, Neoplasm/*genetics

@article {pmid31711023,
year = {2019},
author = {Zhou, J and Tan, H and Bai, Y and Li, J and Lu, Q and Chen, R and Zhang, M and Feng, Q and Wang, M},
title = {Evaluating the HER-2 status of breast cancer using mammography radiomics features.},
journal = {European journal of radiology},
volume = {121},
number = {},
pages = {108718},
doi = {10.1016/j.ejrad.2019.108718},
pmid = {31711023},
issn = {1872-7727},
mesh = {Area Under Curve ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnostic imaging/*genetics ; Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics ; China ; Female ; Genes, erbB-2/*genetics ; Humans ; Mammography/*methods ; Middle Aged ; Preoperative Care ; ROC Curve ; Sensitivity and Specificity ; Support Vector Machine ; },
abstract = {PURPOSE: The aim of our study was to evaluate the HER-2 status in breast cancer patients using mammography (MG) radiomics features.

METHODS: A total of 306 Chinese female patients with invasive ductal carcinoma of no special type (IDC-NST) enrolled from January 2013 to July 2018 were divided into a training set (n = 244) and a testing set (n = 62). One hundred and eighty-six radiomics features were extracted from digital MG images based on the training set. The least absolute shrinkage and selection operator (LASSO) method was used to select the optimal predictive features for HER-2 status from the training set. Both support vector machine (SVM) and logistic regression models were employed based on the selected features. The area under the receiver operating characteristic (ROC) curves (AUCs) of the training set and testing set were used to evaluate the predictive performance of the models.

RESULTS: Compared with the SVM model, the performance of the logistic regression model using a combination of cranial caudal (CC) and mediolateral oblique (MLO) MG views was optimal. In the training set, the sensitivity, specificity, accuracy and area under the curve (AUC) values of the logistic regression model for evaluating HER-2 status based on quantitative radiomics features were 87.29%, 58.73%, 80.00% and 0.846 (95% confidence interval (CI), 0.800-0.887), respectively, and in the testing set, the values were 73.91%, 68.75%, 77.00% and 0.787 (95% CI, 0.673-0.885), respectively.

CONCLUSIONS: Radiomics features could be an efficient tool for the preoperative evaluation of HER-2 status in patients with breast cancer.},
}

Area Under Curve
Breast/diagnostic imaging
Breast Neoplasms/*diagnostic imaging/*genetics
Carcinoma, Ductal, Breast/*diagnostic imaging/*genetics
China
Female
Genes, erbB-2/*genetics
Humans
Mammography/*methods
Middle Aged
Preoperative Care
ROC Curve
Sensitivity and Specificity
Support Vector Machine

@article {pmid31706703,
year = {2019},
author = {Quagliarini, F and Mir, AA and Balazs, K and Wierer, M and Dyar, KA and Jouffe, C and Makris, K and Hawe, J and Heinig, M and Filipp, FV and Barish, GD and Uhlenhaut, NH},
title = {Cistromic Reprogramming of the Diurnal Glucocorticoid Hormone Response by High-Fat Diet.},
journal = {Molecular cell},
volume = {76},
number = {4},
pages = {531-545.e5},
doi = {10.1016/j.molcel.2019.10.007},
pmid = {31706703},
issn = {1097-4164},
support = {R00 CA154887/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Blood Glucose/metabolism ; Chromatin/*metabolism ; *Circadian Clocks/genetics ; *Circadian Rhythm/genetics ; *Diet, High-Fat ; Dietary Fats/administration & dosage/blood/*metabolism ; Disease Models, Animal ; *Energy Metabolism/genetics ; Fasting/metabolism ; Gene Expression Regulation ; Glucocorticoids/metabolism ; Gluconeogenesis ; Ligands ; Liver/*metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/blood/genetics/*metabolism ; PPAR alpha/genetics/metabolism ; Postprandial Period ; Receptors, Glucocorticoid/deficiency/genetics/*metabolism ; STAT5 Transcription Factor/genetics/metabolism ; Secretory Pathway ; Signal Transduction ; Time Factors ; Transcription, Genetic ; Triglycerides/blood ; },
abstract = {The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. We show how GR partitions metabolic processes by time-dependent target gene regulation and controls circulating glucose and triglycerides differentially during feeding and fasting. Highlighting the dominant role GR plays in synchronizing circadian amplitudes, we find that the majority of oscillating genes are bound by and depend on GR. This rhythmic pattern is altered by high-fat diet in a ligand-independent manner. We find that the remodeling of oscillatory gene expression and postprandial GR binding results from a concomitant increase of STAT5 co-occupancy in obese mice. Altogether, our findings highlight GR's fundamental role in the rhythmic orchestration of hepatic metabolism.},
}

Animals
Blood Glucose/metabolism
Chromatin/*metabolism
*Circadian Clocks/genetics
*Circadian Rhythm/genetics
*Diet, High-Fat
Dietary Fats/administration & dosage/blood/*metabolism
Disease Models, Animal
*Energy Metabolism/genetics
Fasting/metabolism
Gene Expression Regulation
Glucocorticoids/metabolism
Gluconeogenesis
Ligands
Liver/*metabolism
Male
Mice, Inbred C57BL
Mice, Knockout
Obesity/blood/genetics/*metabolism
PPAR alpha/genetics/metabolism
Postprandial Period
Receptors, Glucocorticoid/deficiency/genetics/*metabolism
STAT5 Transcription Factor/genetics/metabolism
Secretory Pathway
Signal Transduction
Time Factors
Transcription, Genetic
Triglycerides/blood

@article {pmid31666416,
year = {2019},
author = {Autenshlyus, AI and Davletova, KI and Studenikina, AA and Mikhaylova, ES and Varaksin, NA and Zhurakovsky, IP and Proskura, AV and Sidorov, SV and Lyakhovich, VV},
title = {[Cytokine production by blood immune cells, tumor and its microenvironment, characteristic of extracellular matrix in patients with invasive ductal carcinoma of no special type].},
journal = {Biomeditsinskaia khimiia},
volume = {65},
number = {5},
pages = {424-431},
doi = {10.18097/PBMC20196505424},
pmid = {31666416},
issn = {2310-6972},
mesh = {Breast Neoplasms/*immunology ; Carcinoma, Ductal/*immunology ; Cytokines/*immunology ; *Extracellular Matrix ; Female ; Humans ; Lymphatic Metastasis ; *Tumor Microenvironment ; },
abstract = {The aim of this research was to study cytokine production by blood immune cells, tumor, and its microenvironment, and characterize extracellular matrix of patients with invasive ductal carcinoma of no special type and lymphatic metastases. Spontaneous and polyclonal activators stimulated production of cytokines by blood immune cells, tumor and its microenvironment were studied in 95 patients with invasive ductal carcinoma of no special type. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF and MCP-1 was determined by the solid-phase enzyme-linked immunosorbent assay. The condition of fibrous component and presence of neutral glycoproteins and sulfated glycosaminoglycans were evaluated during the research of extracellular matrix. Regional lymphatic metastases were detected in 35 of 95 patients. It was shown that in the presence or absence of lymphatic metastases index of polyclonal activators influence on the production of cytokines by blood immune cells was different for IL-6, IL-8, and IL-1β; while in the case of cytokine production by tumor and its microenvironment the index of influence was different for IL-2 and IL-17. The presence of lymphatic metastases corresponded with the rise of cytokines spontaneous production, while the absence of lymphatic metastases corresponded with the rise of cytokines production stimulated by polyclonal activators. The value of indices of polyclonal activators influence on the production of cytokines by blood immune cells pointed to the highly stimulating effect of polyclonal activators while the value of indices of polyclonal activators influence on cytokines production by tumor and its microenvironments pointed to the low and sometimes even absent effect of polyclonal activators. Basing on these data we propose a ratio of indices of polyclonal activators influence for the better evaluation of the probability of lymphatic metastases during preoperative period. After characterizing extracellular matrix we found out a point threshold, which, in 100% of cases, predicted the presence of lymphatic metastases basing on the condition of extracellular matrix. Using the data acquired, we are proposing a risk group for metastasis among women with no lymphatic metastases in the moment of check-up.},
}

Breast Neoplasms/*immunology
Carcinoma, Ductal/*immunology
Cytokines/*immunology
*Extracellular Matrix
Female
Humans
Lymphatic Metastasis
*Tumor Microenvironment

@article {pmid31661032,
year = {2019},
author = {Klomek, AB},
title = {Prevention of postpartum suicidality in Israel.},
journal = {Israel journal of health policy research},
volume = {8},
number = {1},
pages = {77},
pmid = {31661032},
issn = {2045-4015},
mesh = {Child ; Female ; Humans ; Israel ; Postpartum Period ; Pregnancy ; Risk Factors ; *Suicide ; USSR ; },
abstract = {Postpartum suicidality in Israel had not been systematically studied until the recent important investigation by Glasser and colleagues. The authors review rates, trends, and characteristics of postpartum women who considered, attempted, or completed suicide in Israel. This commentary argues that, although postpartum suicidality is relatively rare, it is extremely tragic-not just for the women, but for the entire family and community. The main aim of this commentary is to emphasize that preventive efforts should continue and expand, especially among at-risk groups. At-risk groups include the youngest age group, postpartum Arab women, and postpartum former Soviet Union immigrants. Identification of women at risk or suffering from postpartum depression (PPD) is mandated in Israel. Efforts should include broader screening for various types of suicide ideation and behavior. Assessments should specifically include passive suicide ideation, active suicide ideation with method, intent, and plan, as well as various types of suicide attempts and preparatory behaviors. In addition, specific interventions formulated on evidence-based psychotherapies should be provided in family practice, obstetric, and pediatric settings. These settings are less stigmatized in comparison to mental health settings. Potential therapies can be (among others) Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT), which are effective in preventing perinatal depression.},
}

Child
Female
Humans
Israel
Postpartum Period
Pregnancy
Risk Factors
*Suicide
USSR

@article {pmid31660917,
year = {2019},
author = {Peng, Z and Klomek, AB and Li, L and Su, X and Sillanmäki, L and Chudal, R and Sourander, A},
title = {Associations between Chinese adolescents subjected to traditional and cyber bullying and suicidal ideation, self-harm and suicide attempts.},
journal = {BMC psychiatry},
volume = {19},
number = {1},
pages = {324},
pmid = {31660917},
issn = {1471-244X},
mesh = {Adolescent ; Adolescent Behavior ; Bullying/*statistics & numerical data ; Child ; China/epidemiology ; Crime Victims/*statistics & numerical data ; Cyberbullying/statistics & numerical data ; Female ; Humans ; Male ; Prevalence ; Risk Factors ; Self-Injurious Behavior/*epidemiology/etiology ; Students/statistics & numerical data ; *Suicidal Ideation ; Suicide, Attempted/*statistics & numerical data ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: The incidence of bullying is high among adolescents. Adolescents who were victims of bullying have a higher risk of self-harm and suicidal behavior than adolescents who were non-victims. However, research on suicide and both traditional and cyber bullying was limited in China. Therefore, this study examined the associations between Chinese adolescents who were the victims of traditional and cyber bullying and the prevalence of suicidal ideation, self-harm and suicide attempts.

METHODS: This was a population-based study of 2647 students (51.2% girls) with a mean age of 13.6 ± 1.1 years from 10 junior high schools in Shantou, China. Information on bullying victimization, suicidal ideation, self-harm and suicide attempts were collected using a self-administered questionnaire and the psychopathology of the students was assessed using the Strengths and Difficulties Questionnaire (SDQ). The associations were examined with multinomial logistic regression, adjusted for covariates.

RESULTS: Traditional bullying victimization was reported by 16.7% of the adolescents, cyber bullying victimization by 9.0% and both by 3.5%. The prevalence of suicidal ideation was 23.5%, self-harm was 6.2% and suicide attempts was 4.2%. Psychopathology symptoms were risk factors for suicide ideation only, ideation plus self-harm, self-harm only and suicide attempts. Victims of both traditional and cyber bullying had the highest risk of suicidal ideation only, ideation plus self-harm and suicide attempts, compared to those reporting one form of bullying. Victims of cyber bullying only had the second highest risk of suicidal ideation only and suicidal ideation plus self-harm compared to non-victims.

CONCLUSIONS: Adolescents who were victims of both traditional and cyber bullying had greater risks of adverse outcomes of suicidal ideation only, suicidal ideation plus self-harm and suicide attempts. The results of the current study suggest that those exposed to both forms of bullying should be routinely screened for suicidal risk. In addition, school-based anti-bully interventions should also target cyber bullying.},
}

Adolescent
Adolescent Behavior
Bullying/*statistics & numerical data
Child
China/epidemiology
Crime Victims/*statistics & numerical data
Cyberbullying/statistics & numerical data
Female
Humans
Male
Prevalence
Risk Factors
Self-Injurious Behavior/*epidemiology/etiology
Students/statistics & numerical data
*Suicidal Ideation
Suicide, Attempted/*statistics & numerical data
Surveys and Questionnaires

@article {pmid31656498,
year = {2019},
author = {Mohammedi, L and Doula, FD and Mesli, F and Senhadji, R},
title = {Cyclin D1 overexpression in Algerian breast cancer women: correlation with CCND1 amplification and clinicopathological parameters.},
journal = {African health sciences},
volume = {19},
number = {2},
pages = {2140-2146},
pmid = {31656498},
issn = {1729-0503},
mesh = {Adult ; Aged ; Algeria ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cyclin D1/*genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Prognosis ; },
abstract = {Background: Cyclin D1 which is associated with cell cycle regulation is solidly established as an oncogene with an important pathogenetic role in breast carcinomas.

Objectives: The aim of this study was to relate the Cyclin D1 protein overexpression with the amplification of its gene CCND1 in Estrogen Receptors (ER) positive breast carcinomas, in order to investigate the prognostic effect of their aberrations in relation to ER status, also to correlate the Cyclin D1 overexpression with other prognostic parameters.

Materials and methods: Chromogenic in situ hybridization (CISH) was used to identify CCND1 amplification on formalin-fixed paraffin-embedded invasive ductal carcinoma, in which immunohistochemistry (IHC) had previously been performed in order to evaluate the pathological relevance of Cyclin D1 overexpression in human breast cancer (n = 138).

Results: CCND1 amplification was identified in 17/138 (12.3%) tumors and 78/138 (56.5%) tumors have overexpressed Cyclin D1. A significant correlation was identified between CCND1 amplification and Cyclin D1 overexpression (P < 0.001) and both Cyclin D1 and CCND1 were related with ER expression.

Conclusion: Our results show a significant correlation between Cyclin D1 overexpression and CCND1 amplification. Overexpression of Cyclin D1was observed in high proportion of breast cancer which should be considered for routine diagnosis.},
}

Adult
Aged
Algeria
Breast Neoplasms/*genetics
Carcinoma, Ductal, Breast/*genetics
Cyclin D1/*genetics
Female
Gene Amplification
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Middle Aged
Prognosis

@article {pmid31617074,
year = {2020},
author = {Sethy, C and Goutam, K and Nayak, D and Pradhan, R and Molla, S and Chatterjee, S and Rout, N and Wyatt, MD and Narayan, S and Kundu, CN},
title = {Clinical significance of a pvrl 4 encoded gene Nectin-4 in metastasis and angiogenesis for tumor relapse.},
journal = {Journal of cancer research and clinical oncology},
volume = {146},
number = {1},
pages = {245-259},
pmid = {31617074},
issn = {1432-1335},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*blood supply/*genetics/metabolism ; Carcinoma, Ductal, Breast/*blood supply/*genetics/metabolism ; Cell Adhesion Molecules/biosynthesis/*genetics/metabolism ; Female ; Humans ; Middle Aged ; NF-kappa B/metabolism ; Neovascularization, Pathologic/genetics/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; },
abstract = {PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs).

METHODS: Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens.

RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors.

CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p < 0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.},
}

Adult
Aged
Aged, 80 and over
Breast Neoplasms/*blood supply/*genetics/metabolism
Carcinoma, Ductal, Breast/*blood supply/*genetics/metabolism
Cell Adhesion Molecules/biosynthesis/*genetics/metabolism
Female
Humans
Middle Aged
NF-kappa B/metabolism
Neovascularization, Pathologic/genetics/metabolism/pathology
Phosphatidylinositol 3-Kinases/metabolism
Proto-Oncogene Proteins c-akt/metabolism
Signal Transduction

@article {pmid31612916,
year = {2019},
author = {Shimmura, H and Kuramochi, H and Jibiki, N and Katagiri, S and Nishino, T and Araida, T},
title = {Dramatic response of FOLFIRINOX regimen in a collision pancreatic adenocarcinoma patient with a germline BRCA2 mutation: a case report.},
journal = {Japanese journal of clinical oncology},
volume = {49},
number = {11},
pages = {1049-1054},
doi = {10.1093/jjco/hyz141},
pmid = {31612916},
issn = {1465-3621},
mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; BRCA2 Protein/genetics ; Carcinoma, Ductal, Breast/*drug therapy/genetics ; Carcinoma, Pancreatic Ductal/*drug therapy ; Female ; Fluorouracil/therapeutic use ; Genetic Testing ; Germ Cells ; Germ-Line Mutation ; Humans ; Irinotecan/therapeutic use ; Leucovorin/therapeutic use ; Liver Neoplasms/*drug therapy/secondary ; Lymph Node Excision ; Middle Aged ; Mutation ; Oxaliplatin/therapeutic use ; Pancreatic Neoplasms/*drug therapy ; Pancreaticoduodenectomy ; },
abstract = {Germline BRCA1 and BRCA2 mutations are the most common gene mutations in familial pancreatic adenocarcinoma. Several reports have demonstrated the utility of platinum-based chemotherapy for treating cancer patients who harbour a BRCA mutation. Here we discuss a 47-year-old Japanese female with no relevant past history who presented with epigastralgia and fever in September 2016. A computed tomography scan revealed a low-density, low-enhanced tumour 15 mm in diameter in the head of the pancreas. The pathological diagnosis was a ductal pancreatic carcinoma. A 6 mm low-enhanced metastatic tumour was also detected in segment 4 of the liver. Because she had early onset of the disease and a family history-her mother died of pancreatic adenocarcinoma at age 48-we considered a diagnosis of familial pancreatic adenocarcinoma. She received modified FOLFIRINOX. Two months after starting chemotherapy, she was diagnosed with an invasive ductal carcinoma in the right breast. FOLFIRINOX was continued for 8 cycles (4 months); the primary pancreatic adenocarcinoma shrank and the liver metastatic foci disappeared, but the size of the breast tumour increased. Total right breast excision and sentinel lymph node dissection were performed. FOLFIRINOX was continued and after 12 cycles (6 months), both her pancreatic adenocarcinoma and liver metastasis were no longer visible using imaging. Pancreatoduodenectomy was performed and the primary tumour had shrunk to 2.5 mm. Genetic testing revealed a germline BRCA2 mutation. The FOLFIRINOX regimen showed dramatic effects on the collision pancreatic but not on the breast cancer.},
}

Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
BRCA2 Protein/genetics
Carcinoma, Ductal, Breast/*drug therapy/genetics
Carcinoma, Pancreatic Ductal/*drug therapy
Female
Fluorouracil/therapeutic use
Genetic Testing
Germ Cells
Germ-Line Mutation
Humans
Irinotecan/therapeutic use
Leucovorin/therapeutic use
Liver Neoplasms/*drug therapy/secondary
Lymph Node Excision
Middle Aged
Mutation
Oxaliplatin/therapeutic use
Pancreatic Neoplasms/*drug therapy
Pancreaticoduodenectomy

@article {pmid31594782,
year = {2019},
author = {Jakharia-Shah, A and Wheatley, H and Beesley, M},
title = {Reminder of an important clinical lesson: breast cancer metastasis to the parotid gland.},
journal = {BMJ case reports},
volume = {12},
number = {10},
pages = {},
doi = {10.1136/bcr-2018-226494},
pmid = {31594782},
issn = {1757-790X},
mesh = {Biopsy, Fine-Needle/methods ; Breast Neoplasms/complications/diagnostic imaging/pathology/*secondary ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Parotid Gland/*pathology/surgery ; Parotid Neoplasms/pathology/*secondary/surgery ; Positron Emission Tomography Computed Tomography/methods ; Receptor, ErbB-2/metabolism ; Treatment Outcome ; },
abstract = {A 59-year-old woman presented to an otolaryngology clinic with an 8-week history of a painless lump over her left parotid gland. Her medical history included an invasive ductal carcinoma (33 mm) and a ductal carcinoma in situ (70 mm) of the right breast, for which she had a mastectomy and various adjuvant therapies. The primary tumour presented 8 years prior to the metachronous metastasis. This patient was a non-smoker and had no significant family history. Post-superficial parotidectomy pathology revealed the parotid gland tumour to be oestrogen receptor-positive and HER2 receptor-positive, thus ruling out the initial differential diagnosis of a pleomorphic adenoma. A consequential total parotidectomy with a posterolateral neck dissection was performed with sparing of the facial nerve. The patient recovered well having only encountered a self-resolving salivary fistula. She portrayed no signs of facial nerve palsy and subsequent imaging scans showed no abnormalities.},
}

Biopsy, Fine-Needle/methods
Breast Neoplasms/complications/diagnostic imaging/pathology/*secondary
Diagnosis, Differential
Female
Humans
Middle Aged
Parotid Gland/*pathology/surgery
Parotid Neoplasms/pathology/*secondary/surgery
Positron Emission Tomography Computed Tomography/methods
Receptor, ErbB-2/metabolism
Treatment Outcome

@article {pmid31584185,
year = {2020},
author = {Xu, Q and Rangaswamy, US and Wang, W and Robbins, SH and Harper, J and Jin, H and Cheng, X},
title = {Evaluation of Newcastle disease virus mediated dendritic cell activation and cross-priming tumor-specific immune responses ex vivo.},
journal = {International journal of cancer},
volume = {146},
number = {2},
pages = {531-541},
doi = {10.1002/ijc.32694},
pmid = {31584185},
issn = {1097-0215},
mesh = {Animals ; Chlorocebus aethiops ; Coculture Techniques ; *Cross-Priming ; Dendritic Cells/*immunology/metabolism ; Female ; HeLa Cells ; Humans ; Immunotherapy/*methods ; Interferon Type I/immunology/metabolism ; Neoplasms/immunology/*therapy ; Newcastle disease virus/genetics/immunology ; Oncolytic Virotherapy/*methods ; Oncolytic Viruses/genetics/immunology ; RNA/administration & dosage/genetics ; RNA, Viral/administration & dosage/genetics ; T-Lymphocytes/immunology ; Vero Cells ; },
abstract = {We have developed an oncolytic Newcastle disease virus (NDV) that has potent in vitro and in vivo anti-tumor activities and attenuated pathogenicity in chickens. In this ex vivo study using the same recombinant NDV backbone with GFP transgene (NDV-GFP, designated as rNDV), we found that rNDV induces maturation of monocyte-derived immature dendritic cells (iDCs) by both direct and indirect mechanisms, which promote development of antigen-specific T cell responses. Addition of rNDV directly to iDCs culture induced DC maturation, as demonstrated by the increased expression of costimulatory and antigen-presenting molecules as well as the production of type I interferons (IFNs). rNDV infection of the HER-2 positive human breast cancer cell line (SKBR3) resulted in apoptotic cell death, release of proinflammatory cytokines, and danger-associated molecular pattern molecules (DAMPs) including high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70). Addition of rNDV-infected SKBR3 cells to iDC culture resulted in greatly enhanced upregulation of the maturation markers and release of type I IFNs by DCs than rNDV-infected DCs only. When co-cultured with autologous T cells, DCs pre-treated with rNDV-infected SKBR3 cells cross-primed T cells in an antigen-specific manner. Altogether, our data strongly support the potential of oncolytic NDV as efficient therapeutic agent for cancer treatment.},
}

Animals
Chlorocebus aethiops
Coculture Techniques
*Cross-Priming
Dendritic Cells/*immunology/metabolism
Female
HeLa Cells
Humans
Immunotherapy/*methods
Interferon Type I/immunology/metabolism
Neoplasms/immunology/*therapy
Newcastle disease virus/genetics/immunology
Oncolytic Virotherapy/*methods
Oncolytic Viruses/genetics/immunology
RNA/administration & dosage/genetics
RNA, Viral/administration & dosage/genetics
T-Lymphocytes/immunology
Vero Cells

@article {pmid31576258,
year = {2019},
author = {Marsili, C and Wilson, CM and Gura, N},
title = {Prospective Surveillance Screenings to Identify Physical Therapy Needs During Breast Cancer Diagnosis and Surviviorship: A Case Report.},
journal = {Cureus},
volume = {11},
number = {7},
pages = {e5265},
pmid = {31576258},
issn = {2168-8184},
abstract = {Breast cancer and its treatments can cause detrimental effects to function and quality of life (QoL). These patients do not conventionally receive physical therapy services until impairments and functional limitations have become extensive. Emerging treatment models advocate for early rehabilitation screenings and proactive interventions, which are termed prospective surveillance. The purpose of this case report was to describe two prospective surveillance screenings at initial diagnosis and survivorship and subsequent physical therapy episodes of care for a patient with breast cancer. A 39-year-old female was diagnosed with invasive ductal carcinoma of the right breast. Approximately three months after the initial diagnosis, the patient had a right nipple-sparing mastectomy and immediate reconstruction with an expander. In addition, one lymph node was removed and underwent a biopsy, which was negative for metastases. The patient was screened by a physical therapist after her initial cancer diagnosis at the breast multidisciplinary clinic. This was after her mastectomy with an expander; the therapist recommended an episode of outpatient physical therapy due to impairments in pain, fatigue, loss of range of motion, weakness, and limitations in performance of her activities of daily living. The patient was seen initially for five visits. She underwent her final reconstructive surgery one month after discharge from physical therapy. Six months after her final reconstructive surgery, she was screened by the same physical therapist in the cancer survivorship clinic. Once again, therapy was recommended due to pain as well as deficits to her range of motion, strength, and functional status. The second episode of care lasted 14 visits and the patient showed improvements in pain, range of motion, shoulder strength and gains in the patient-specific functional scale and upper extremity functional index. This case reflects the importance of prospective surveillance screenings to overall patient outcomes. This patient may not have otherwise received physical therapy and its associated benefits without the prospective screenings by the physical therapist.},
}

@article {pmid31539353,
year = {2019},
author = {Gonzalez, SM and Aguilar-Jimenez, W and Alvarez, N and Rugeles, MT},
title = {Cholecalciferol modulates the phenotype of differentiated monocyte-derived dendritic cells without altering HIV-1 transfer to CD4+ T cells.},
journal = {Hormone molecular biology and clinical investigation},
volume = {40},
number = {1},
pages = {},
doi = {10.1515/hmbci-2019-0003},
pmid = {31539353},
issn = {1868-1891},
mesh = {CD4-Positive T-Lymphocytes/*drug effects/immunology/virology ; Cells, Cultured ; Cholecalciferol/*pharmacology ; Dendritic Cells/*drug effects/immunology/virology ; HIV Infections/*immunology/prevention & control/transmission/virology ; HIV-1/*drug effects/immunology/physiology ; Humans ; Immunologic Factors/pharmacology ; Monocytes/drug effects/immunology/virology ; Virus Internalization/drug effects ; Vitamins/*pharmacology ; },
abstract = {Background Dendritic cells (DCs) play a crucial role during HIV-1 transmission due to their ability to transfer virions to susceptible CD4+ T cells, particularly in the lymph nodes during antigen presentation which favors the establishment of systemic infection. As mature dendritic cells (mDCs) exhibit a greater ability to transfer virions, compared to immature DCs (iDCs), maintenance of an iDC phenotype could decrease viral transmission. The immunomodulatory vitamin D (VitD) has been shown to reduce activation and maturation of DCs; hence, we hypothesized that it would reduce viral transference by DCs. Materials and methods We evaluated the effect of in vitro treatment with a precursor of VitD, cholecalciferol, on the activation/maturation phenotype of differentiated monocyte-derived DCs and their ability to transfer HIV-1 to autologous CD4+ T cells. Results Our findings show that although cholecalciferol decreases the activation of iDCs, it did not impact the maturation phenotype after LPS treatment nor iDCs' ability to transfer viral particles to target cells. Conclusion These findings suggest that despite cholecalciferol potentially modulates the phenotype of mucosal iDCs in vivo, such modulation might not impact the ability of these cells to transfer HIV-1 to target CD4+ T cells.},
}

CD4-Positive T-Lymphocytes/*drug effects/immunology/virology
Cells, Cultured
Cholecalciferol/*pharmacology
Dendritic Cells/*drug effects/immunology/virology
HIV Infections/*immunology/prevention & control/transmission/virology
HIV-1/*drug effects/immunology/physiology
Humans
Immunologic Factors/pharmacology
Monocytes/drug effects/immunology/virology
Virus Internalization/drug effects
Vitamins/*pharmacology

@article {pmid31512354,
year = {2020},
author = {Ali Mlees, M},
title = {Diagnosis and surgical treatment of pathologic nipple discharge using ultrasound-guided wire localization of focal ductal dilatation.},
journal = {The breast journal},
volume = {26},
number = {2},
pages = {139-143},
doi = {10.1111/tbj.13493},
pmid = {31512354},
issn = {1524-4741},
abstract = {Nipple discharge is the third breast complaint after pain and lumps. The modern high-resolution ultrasound techniques are becoming more sensitive for the visualization of intraductal changes especially focal ductal dilatation (FDD), hypothesized as a radiographic manifestation of the lesion itself and that ultrasound-guided wire localization of this finding would enable identification and excision of the causative lesion. The aim of this study was to evaluate the safety, feasibility, efficiency and outcome of ultrasound-guided wire localization of FDD as possible cause of pathological nipple discharge (PND). The present study was conducted on 56 patients with PND presented to Surgical Oncology Unit at General Surgery Department, Tanta University Hospital from January 2018 to January 2019. The patients subjected to ultrasound-guided wire localization of FDD on the day of surgery, the involved duct was cannulated with a lacrimal duct probe, the targeted tissue was excised, and the specimen was sent for histopathological examination. The patients' age ranged between 26 and 71 years with a mean age of 48 years. The bloody nipple discharge was the commonest presenting symptom in 44 out of 56 patients (78.5%). The duct dilatation on study ultrasound ranged from 2.1 to 3.7 mm with a mean of 2.6 mm. Preoperative ultrasound-guided wire localization of the site of FDD was successfully performed in all cases. Papilloma alone founded in 40 out of 56 patients (71.4%), papilloma + ductal carcinoma in situ (DCIS) in six patients (10.7%), papilloma + invasive ductal carcinoma in six patients (10.7%), DCIS in two patients (3.6%) and duct ectasia in two patients (3.6%). Ultrasound-guided wire localization of FDD is an easy and safe technique for evaluation, precise localization, and targeted excision of the underlying lesions of PND.},
}

@article {pmid31508769,
year = {2019},
author = {Couto, MSA and Firme, VAC and Guerra, MR and Bustamante-Teixeira, MT},
title = {The effect of redistribution of ill-defined causes of death on the mortality rate of breast cancer in Brazil.},
journal = {Ciencia & saude coletiva},
volume = {24},
number = {9},
pages = {3517-3528},
doi = {10.1590/1413-81232018249.31402017},
pmid = {31508769},
issn = {1678-4561},
mesh = {Brazil/epidemiology ; Breast Neoplasms/*mortality ; Cause of Death/*trends ; Cities/statistics & numerical data ; Female ; Humans ; Mortality/*trends ; },
abstract = {The relevance of breast cancer for women has driven research about mortality of this disease. However, these studies are affected by problems generated by deaths due to ill-defined causes (IDC). To highlight distortions caused by IDC in studies that evaluate mortality, we calculated the age-standardized mortality rates of breast cancer, with and without adjustment for IDC for the years 1990, 2000, and 2010. Then, panel data regression models were estimated and enabled us to identify that the adjustment for IDC: has elevated breast cancer mortality rate of Brazilian municipalities by 9% in the period considered; has drawn mortality rates of the South, Southeast, Northeast and North regions closer; has reduced the increasing trend of mortality by almost 60%, mainly in the Southeast and South regions; has increased, more sharply, the mortality in cities with less than 5 thousand inhabitants; has curbed the significance of most factors associated with breast cancer; has revealed that the effect of longevity and the public health expenditure may be overestimated. These results highlight the importance of adjustment for IDC in producing reliable mortality indicators.},
}

Brazil/epidemiology
Breast Neoplasms/*mortality
Cause of Death/*trends
Cities/statistics & numerical data
Female
Humans
Mortality/*trends

@article {pmid31488082,
year = {2019},
author = {McQuerry, JA and Jenkins, DF and Yost, SE and Zhang, Y and Schmolze, D and Johnson, WE and Yuan, Y and Bild, AH},
title = {Pathway activity profiling of growth factor receptor network and stemness pathways differentiates metaplastic breast cancer histological subtypes.},
journal = {BMC cancer},
volume = {19},
number = {1},
pages = {881},
pmid = {31488082},
issn = {1471-2407},
support = {P30 CA033572/CA/NCI NIH HHS/United States ; U54 CA209978/CA/NCI NIH HHS/United States ; U54CA209978/NH/NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Bcl-2-Like Protein 11/metabolism ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cohort Studies ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Osteonectin/genetics ; Phenotype ; Prognosis ; RNA-Seq/methods ; Receptors, Growth Factor/*metabolism ; Signal Transduction/*genetics ; Snail Family Transcription Factors/metabolism ; Transcriptome/*genetics ; Triple Negative Breast Neoplasms/*genetics/pathology ; },
abstract = {BACKGROUND: Gene expression profiling of rare cancers has proven challenging due to limited access to patient materials and requirement of intact, non-degraded RNA for next-generation sequencing. We customized a gene expression panel compatible with degraded RNA from formalin-fixed, paraffin-embedded (FFPE) patient cancer samples and investigated its utility in pathway activity profiling in patients with metaplastic breast cancer (MpBC).

METHODS: Activity of various biological pathways was profiled in samples from nineteen patients with MpBC and 8 patients with invasive ductal carcinoma with triple negative breast cancer (TNBC) phenotype using a custom gene expression-based assay of 345 genes.

RESULTS: MpBC samples of mesenchymal (chondroid and/or osteoid) histology demonstrated increased SNAI1 and BCL2L11 pathway activity compared to samples with non-mesenchymal histology. Additionally, late cornified envelope and keratinization genes were downregulated in MpBC compared to TNBC, and epithelial-to-mesenchymal transition (EMT) and collagen genes were upregulated in MpBC. Patients with high activity of an invasiveness gene expression signature, as well as high expression of the mesenchymal marker and extracellular matrix glycoprotein gene SPARC, experienced worse outcomes than those with low invasiveness activity and low SPARC expression.

CONCLUSIONS: This study demonstrates the utility of gene expression profiling of metaplastic breast cancer FFPE samples with a custom counts-based assay. Gene expression patterns identified by this assay suggest that, although often histologically triple negative, patients with MpBC have distinct pathway activation compared to patients with invasive ductal TNBC. Incorporation of targeted therapies may lead to improved outcome for MpBC patients, especially in those patients expressing increased activity of invasiveness pathways.},
}

Adult
Aged
Aged, 80 and over
Bcl-2-Like Protein 11/metabolism
Carcinoma, Ductal, Breast/*genetics/pathology
Cohort Studies
Epithelial-Mesenchymal Transition/genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Middle Aged
Osteonectin/genetics
Phenotype
Prognosis
RNA-Seq/methods
Receptors, Growth Factor/*metabolism
Signal Transduction/*genetics
Snail Family Transcription Factors/metabolism
Transcriptome/*genetics
Triple Negative Breast Neoplasms/*genetics/pathology

@article {pmid31437176,
year = {2019},
author = {Santos Junior, OR and da Costa Rocha, MO and Rodrigues de Almeida, F and Sales da Cunha, PF and Souza, SCS and Saad, GP and Santos, TADQ and Ferreira, AM and Tan, TC and Nunes, MCP},
title = {Speckle tracking echocardiographic deformation indices in Chagas and idiopathic dilated cardiomyopathy: Incremental prognostic value of longitudinal strain.},
journal = {PloS one},
volume = {14},
number = {8},
pages = {e0221028},
pmid = {31437176},
issn = {1932-6203},
mesh = {Adult ; Aged ; Cardiomyopathy, Dilated/complications/*diagnostic imaging/mortality/physiopathology ; Chagas Cardiomyopathy/complications/*diagnostic imaging/mortality/physiopathology ; Female ; Follow-Up Studies ; Heart Failure/*diagnostic imaging/etiology/mortality/physiopathology ; Heart Transplantation/statistics & numerical data ; Hospitalization/statistics & numerical data ; Humans ; Male ; Middle Aged ; Prognosis ; Stroke Volume/physiology ; Survival Analysis ; Ventricular Function, Left/physiology ; },
abstract = {BACKGROUND: Chagas cardiomyopathy (CDC) is associated with a poor prognosis compared to other cardiomyopathies. Speckle tracking echocardiography (STE), which provides direct assessment of myocardial fiber deformation, may be useful in predicting prognosis.

OBJECTIVE: This study assessed STE in CDC and compared with idiopathic cardiomyopathy (IDC), and also examined the incremental prognostic information of STE over left ventricular ejection fraction (LVEF) in these patients.

METHODS: We enrolled 112 patients, age of 56.7 ± 11.8 years, 81 with CDC and 31 with IDC. STE indices were obtained at baseline in all patients. The endpoint was a composite of death, hospitalization for heart failure, or need for heart transplantation.

RESULTS: Patients with IDC had worse LV systolic function compared to CDC, with LVEF of 34.5% vs 41.3%, p = 0.004, respectively. After adjustment for LVEF, there were no differences in STE values between CDC and IDC. During a median follow-up of 18.2 months (range, 11 to 22), 26 patients met the composite end point (24%). LV longitudinal strain was a strong predictor of adverse events, incremental to LVEF and E/e' ratio (HR 1.463, 95% CI 1.130-1.894; p = 0.004). The risk of cardiac events increased significantly in patients with GLS > - 12% (log-rank p = 0.035).

CONCLUSIONS: STE indices were abnormal in patients with dilated cardiomyopathy, without differences between CDC and IDC. LV longitudinal strain was a powerful predictor of outcome, adding prognostic information beyond that provided by LVEF and E/e' ratio.},
}

Adult
Aged
Cardiomyopathy, Dilated/complications/*diagnostic imaging/mortality/physiopathology
Chagas Cardiomyopathy/complications/*diagnostic imaging/mortality/physiopathology
Female
Follow-Up Studies
Heart Failure/*diagnostic imaging/etiology/mortality/physiopathology
Heart Transplantation/statistics & numerical data
Hospitalization/statistics & numerical data
Humans
Male
Middle Aged
Prognosis
Stroke Volume/physiology
Survival Analysis
Ventricular Function, Left/physiology

@article {pmid31427562,
year = {2019},
author = {Sun, Y and Lei, B and Huang, Q},
title = {SOX18 Affects Cell Viability, Migration, Invasiveness, and Apoptosis in Hepatocellular Carcinoma (HCC) Cells by Participating in Epithelial-to-Mesenchymal Transition (EMT) Progression and Adenosine Monophosphate Activated Protein Kinase (AMPK)/Mammalian Target of Rapamycin (mTOR).},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {25},
number = {},
pages = {6244-6254},
pmid = {31427562},
issn = {1643-3750},
mesh = {Adenylate Kinase/*metabolism ; Apoptosis/physiology ; Carcinoma, Hepatocellular/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Cell Survival/physiology ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms/genetics/*metabolism/*pathology ; Neoplasm Invasiveness ; SOXF Transcription Factors/*metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism ; },
abstract = {BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. It has been verified that the expression of SOX18 is correlated to poor clinical prognosis in patients with ovarian cancer, non-small cell lung cancer, or breast invasive ductal carcinoma. However, the expression pattern and biological function of SOX18 in HCC tissues remains unclear. In this study, we set out to investigate the associated biological function and potential molecular mechanism of the SOX18 gene in HCC cells. MATERIAL AND METHODS The mRNA and protein expression levels of experimental related genes were detected by real-time polymerase chain reaction and western blotting assay, respectively. The MTT method was used to assess cell viability, and cell apoptosis analysis was performed by means of FACScan flow cytometry. Wound-healing assay and Transwell analysis were performed to evaluate the ability of cell migration and invasiveness, respectively. RESULTS SOX18 was highly expressed in various HCC cell lines. In addition, SOX18 promoted cell viability, migration, and invasion and simultaneously induce cell apoptosis. SOX18 promoted epithelial-to-mesenchymal transition (EMT) progression, and SOX18 downregulation activated the autophagy signaling pathway AMPK/mTOR in HCC cells. CONCLUSIONS SOX18 downregulation in HCC cells suppressed cell viability and metastasis, induced cell apoptosis and hindered the occurrence and progression of tumor cells by participating in the EMT process and regulating the autophagy signaling pathway AMPK/mTOR.},
}

Adenylate Kinase/*metabolism
Apoptosis/physiology
Carcinoma, Hepatocellular/genetics/*metabolism/*pathology
Cell Line, Tumor
Cell Movement/physiology
Cell Proliferation/physiology
Cell Survival/physiology
Epithelial-Mesenchymal Transition
Humans
Liver Neoplasms/genetics/*metabolism/*pathology
Neoplasm Invasiveness
SOXF Transcription Factors/*metabolism
Signal Transduction
TOR Serine-Threonine Kinases/*metabolism

@article {pmid31391072,
year = {2019},
author = {Tan, X and Li, Z and Ren, S and Rezaei, K and Pan, Q and Goldstein, AT and Macri, CJ and Cao, D and Brem, RF and Fu, SW},
title = {Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer.},
journal = {Breast cancer research : BCR},
volume = {21},
number = {1},
pages = {89},
pmid = {31391072},
issn = {1465-542X},
mesh = {3' Untranslated Regions ; Breast Neoplasms/*genetics/*pathology/therapy ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*genetics ; DNA Damage ; Disease Progression ; Drug Resistance, Neoplasm/*genetics ; Epithelial-Mesenchymal Transition/genetics ; Female ; Forkhead Box Protein M1/genetics ; *Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Humans ; MicroRNAs/*genetics ; Models, Biological ; RNA Interference ; Radiation Tolerance/*genetics ; },
abstract = {BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment.

METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed.

RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability.

CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management.},
}

3' Untranslated Regions
Breast Neoplasms/*genetics/*pathology/therapy
Cell Line, Tumor
Cell Transformation, Neoplastic/*genetics
DNA Damage
Disease Progression
Drug Resistance, Neoplasm/*genetics
Epithelial-Mesenchymal Transition/genetics
Female
Forkhead Box Protein M1/genetics
*Gene Expression Regulation, Neoplastic
Genes, Reporter
Humans
MicroRNAs/*genetics
Models, Biological
RNA Interference
Radiation Tolerance/*genetics

@article {pmid31390230,
year = {2019},
author = {Ortega, A and Olea-Herrero, N and Arenas, MI and Vélez-Vélez, E and Moreno-Gómez-Toledano, R and Muñoz-Moreno, C and Lázaro, A and Esbrit, P and Tejedor, A and Bosch, RJ},
title = {Urinary excretion of parathyroid hormone-related protein correlates with renal function in control rats and rats with cisplatin nephrotoxicity.},
journal = {American journal of physiology. Renal physiology},
volume = {317},
number = {4},
pages = {F874-F880},
doi = {10.1152/ajprenal.00091.2019},
pmid = {31390230},
issn = {1522-1466},
mesh = {Acute Kidney Injury/*chemically induced/pathology/*urine ; Animals ; Antineoplastic Agents/*toxicity ; Biomarkers/urine ; Cisplatin/*toxicity ; Creatinine/urine ; Kidney/pathology ; Kidney Function Tests ; Male ; Parathyroid Hormone-Related Protein/*urine ; Rats ; Rats, Wistar ; },
abstract = {Parathyroid hormone-related protein (PTHrP) and its receptor are abundantly expressed throughout the renal parenchyma, where PTHrP exerts a modulatory action on renal function. PTHrP upregulation is a common event associated with the mechanism of renal injury and repair. However, no study has yet explored the putative excretion of PTHrP in urine, including its potential relationship with renal function. In the present study, we tested this hypothesis by studying the well-known rat model of acute renal injury induced by the chemotherapeutic agent cisplatin. Using Western blot analysis, we could detect a single protein band, corresponding to intact PTHrP, in the urine of both control and cisplatin-injected rats, whose levels were significantly higher in the latter group. PTHrP was detected in rat urine by dot blot, and its quantification with two specific ELISA kits showed that, compared with control rats, those treated with cisplatin displayed a significant increase in urinary PTHrP (expressed as the PTHrP-to-creatinine ratio or 24-h excretion). In addition, a positive correlation between urinary PTHrP excretion and serum creatinine was found in these animals. In conclusion, our data demonstrate that PTHrP is excreted in rat urine and that this excretion is higher with the decrease of renal function. This suggests that urinary PTHrP levels might be a renal function marker.},
}

Acute Kidney Injury/*chemically induced/pathology/*urine
Animals
Antineoplastic Agents/*toxicity
Biomarkers/urine
Cisplatin/*toxicity
Creatinine/urine
Kidney/pathology
Kidney Function Tests
Male
Parathyroid Hormone-Related Protein/*urine
Rats
Rats, Wistar

@article {pmid31357083,
year = {2019},
author = {Arabpour, M and Rasolmali, R and Talei, AR and Mehdipour, F and Ghaderi, A},
title = {Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes.},
journal = {Molecular immunology},
volume = {114},
number = {},
pages = {172-178},
doi = {10.1016/j.molimm.2019.07.019},
pmid = {31357083},
issn = {1872-9142},
mesh = {Adult ; Aged ; B-Lymphocytes/*immunology ; Breast Neoplasms/*immunology ; CD40 Ligand/immunology ; Carcinoma, Ductal/immunology ; Female ; Granzymes/*immunology ; Humans ; Interleukins/immunology ; Lymph Nodes/*immunology ; Lymphocyte Activation/*immunology ; Middle Aged ; Perforin/immunology ; },
abstract = {B lymphocytes with regulatory or effector functions synthesize granzyme B (GZMB). We investigated the frequency and phenotype of GZMB-producing B cells in breast tumor-draining lymph nodes (TDLNs). Mononuclear cells were isolated from 48 axillary lymph nodes and were stimulated with anti-BCR (B cell receptor), recombinant interleukin (IL)-21 and CD40 L alone or in combination. Flow cytometry was used to evaluate the expression of GZMB in B cells, and in 4 samples the phenotype of GZMB+ B cells was determined. B cells produced GZMB only when stimulated with a combination of IL-21 and anti-BCR for at least 16 h. Adding CD40 L to IL-21 and anti-BCR stimuli resulted in lower GZMB production in B cells. A small fraction of B cells was able to produce perforin in all stimulation conditions, and the majority of GZMB+ B cells were perforin-negative. Both naïve (CD24lowCD27-) and active/memory (CD24hiCD27+) B cells expressed GZMB. In patients with invasive ductal carcinoma, the frequency of GZMB+ B cells was significantly lower in metastatic compared to non-metastatic lymph nodes. The frequency of GZMB+ B cells did not significantly correlate with prognostic factors such as stage, tumor size or Her2 expression. In summary, a subpopulation of both naïve and memory B cells expressed GZMB in breast TDLNs. Our findings underscore the need to investigate the function of GZMB+ B cells in breast tumor immunity.},
}

Adult
Aged
B-Lymphocytes/*immunology
Breast Neoplasms/*immunology
CD40 Ligand/immunology
Carcinoma, Ductal/immunology
Female
Granzymes/*immunology
Humans
Interleukins/immunology
Lymph Nodes/*immunology
Lymphocyte Activation/*immunology
Middle Aged
Perforin/immunology