@article {pmid42719958,
year = {2026},
author = {Saito, M and Tsuzuki, H and Hosomi, A},
title = {Investigating Translocation Mechanisms of TDP-43 Into the Endoplasmic Reticulum Using Budding Yeast Models.},
journal = {Traffic (Copenhagen, Denmark)},
volume = {27},
number = {3},
pages = {e70054},
doi = {10.1111/tra.70054},
pmid = {42719958},
issn = {1600-0854},
support = {21K05502//Japan Society for the Promotion of Science/ ; 4-0012//Ohsumi Frontier Science Foundation/ ; },
mesh = {*Endoplasmic Reticulum/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Protein Transport/physiology ; Protein Sorting Signals ; Saccharomyces cerevisiae Proteins/metabolism/genetics ; *Saccharomyces cerevisiae/metabolism ; Glycosylation ; *Saccharomycetales/metabolism ; },
abstract = {Signal peptides direct secretory and membrane proteins to the endoplasmic reticulum (ER), but proteins lacking classical signal peptides can occasionally engage the ER translocation machinery. TDP-43 is a nuclear RNA-binding protein implicated in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. TDP-43 pathology has been linked to extracellular TDP-43 species, association with the ER luminal oxidoreductase PDI, and ER stress-related phenotypes, yet whether TDP-43 fragments can directly access the ER lumen remains unclear. Here, we used budding yeast to examine signal peptide-independent ER entry of TDP-43. C-terminal fragments of TDP-43 acquired N-glycans in ste24Δ cells, whereas full-length TDP-43 showed little detectable ER entry. Endo H digestion confirmed N-glycosylation of the fragments, and a protease protection assay supported ER luminal localization of TDP-43(Δ2-89). ER entry was reduced by sec61-41 and sec66Δ, indicating engagement of a Sec61/Sec66-dependent translocation pathway. Deletion analyses identified opposing sequence elements: residues 320-343 facilitated ER entry, whereas an N-terminal region upstream of the nuclear localization signal suppressed it. TDP-43(Δ2-89) also accessed the secretory pathway, and selected disease-associated variants caused Ire1-dependent growth vulnerability without increasing detectable ER translocation. These findings reveal a Ste24-suppressed route for noncanonical ER entry of TDP-43 fragments.},
}

*Endoplasmic Reticulum/metabolism
*DNA-Binding Proteins/metabolism/genetics
Protein Transport/physiology
Protein Sorting Signals
Saccharomyces cerevisiae Proteins/metabolism/genetics
*Saccharomyces cerevisiae/metabolism
Glycosylation
*Saccharomycetales/metabolism

@article {pmid42720086,
year = {2026},
author = {Benatar, M and Huey, ED and Onyike, CU and McHutchison, C and Tartaglia, MC and Barker, MS and Abrahams, S and De Vocht, J and Rhodes, E and Pijnenburg, YA and Turner, MR and van Damme, P and Lee, EB and Wuu, J and Benussi, A and Boeve, BF and McMillan, CT and Strong, MJ},
title = {Conceptualizing cognition and behaviour across amyotrophic lateral sclerosis and frontotemporal dementia.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag300},
pmid = {42720086},
issn = {1460-2156},
abstract = {Cognitive and behavioral dysfunction in frontotemporal dementia (FTD) evolves along a clinical continuum from a clinically silent stage of disease, through a prodromal period, often referred to as mild cognitive impairment (MCI) and/or mild behavioral impairment (MBI), and into a clinically manifest stage recognized by the syndromes of behavioral variant FTD and primary progressive aphasia (PPA). Similar cognitive and behavioral manifestations of varying severity are also encountered in individuals with amyotrophic lateral sclerosis (ALS). Notwithstanding this phenotypic overlap as well as a degree of shared genetic risk and underlying pathology, the approach to phenotypic characterization and description meaningfully differs between the ALS and FTD communities. The problem is particularly evident within the ALS community when describing impairment in the prodromal vs. clinically manifest disease stages. Pertinent considerations include the nature of cognitive and behavioral assessments, the nosology used to describe symptoms identified including those encompassed by the terms 'behavioral' and 'neuropsychiatric', the operationalized criteria that define prodromal syndromes and clinically manifest disease, and the extent to which these criteria rely on longitudinal (vs. cross-sectional) data. A multi-stakeholder workshop, held in London, Ontario (May 12-14, 2025), brought together neurologists, psychiatrists, neuropsychologists, neuropathologists, neuroscientists, and neurogeneticists studying ALS and FTD, to promote inter-disciplinary dialogue and to define a research agenda that might be jointly tackled to address these critical issues. A new nosology for classifying frontotemporal-related behavioral and neuropsychiatric dysfunction, which could be used to support empirical evidence collection, is proposed alongside a list of cognitive, language, behavioral and neuropsychiatric symptoms to be considered in the evaluation of individuals with ALS. Research priorities for each of the ALS and FTD communities, as well as initiatives that should be undertaken jointly, are highlighted. The long-term goal is to harmonize approaches to phenotypic characterization, the nosology used to describe symptoms, and the criteria used to define landmark stages along the clinical continua of the motor neuron and frontotemporal axes irrespective of clinical stage.},
}

@article {pmid42720300,
year = {2026},
author = {Li, S and Xia, X and Wei, Z and Wang, N and Lin, H and Niu, L},
title = {Generation of Herbicide-Resistant Alfalfa Germplasm via Prime Editing.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
pmid = {42720300},
issn = {1467-7652},
support = {32325035//National Natural Science Foundation of China/ ; },
abstract = {Alfalfa (Medicago sativa) is the most widely cultivated forage crop worldwide, owing to its high protein content, balanced amino acid profile, and abundance of vitamins and minerals. However, weed infestation severely threatens alfalfa yield and quality. The lack of herbicide‑resistant cultivars, combined with the diversity of weed species, has made herbicide tolerance a key breeding objective. To address this challenge, we developed a highly optimized prime editing system and, for the first time, achieved prime editing in alfalfa by enhancing the expression efficiency of its components. Specifically, we introduced mutations in three target genes MsALS1, MsALS2 and MsACC1 to confer herbicide resistance: mutations in MsALS1 and MsALS2 were designed to confer resistance to ALS‑inhibiting herbicides (based on evidence from their rice homologs), while those in MsACC1 were targeted to confer resistance to aryloxyphenoxypropionate (APP) herbicides. Using the Csy4 nuclease system, we performed simultaneous prime editing of all three genes, ultimately generating alfalfa lines resistant to nicosulfuron and haloxyfop‑P‑methyl. This study represents the first successful multi‑gene prime editing in alfalfa, providing a novel tool and a valuable approach for alfalfa molecular breeding.},
}

@article {pmid42713005,
year = {2026},
author = {Belaidi, AA and Furtado, DL and Alves, F and Nisbet, RM and Ayton, S and Bush, AI},
title = {Engineering mRNA-LNP Medicines for the Ageing Brain: Opportunities and Challenges for Neurodegenerative Diseases.},
journal = {Exploration (Beijing, China)},
volume = {},
number = {},
pages = {70223},
pmid = {42713005},
issn = {2766-2098},
abstract = {Messenger RNA (mRNA) therapeutics delivered by lipid nanoparticles (LNPs) have advanced from concept to clinic at unprecedented speed, yet their promise for neurodegenerative diseases remains largely untapped. Currently intractable age-related proteinopathies such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis demand new therapies that combine molecular precision with scalable manufacturing. This review surveys recent advances in engineering LNPs that traverse the blood-brain barrier (BBB), evade innate immune surveillance, and achieve cell-selective expression in the ageing brain. We highlight emerging chemistries, including BBB-shuttling ionizable lipids, peptide-functionalized shells, and liver-detargeted formulations that enable systemic or minimally invasive delivery to the central nervous system (CNS) in animal models. Although no CNS-directed mRNA-LNP has yet reached clinical trials, first-in-human studies for rare metabolic disorders demonstrate favourable safety, manufacturability, and durable protein replacement. Drawing lessons from COVID-19 mRNA vaccines and ongoing liver-targeted programmes, we outline a translational roadmap for brain applications. Major hurdles that are critically assessed include efficient endosomal escape in aged neurons, heterogeneity of the senescent BBB, chronic-dose immunogenicity, and large-scale synthesis of next-generation lipids. Finally, we propose design rules and analytical standards to address outstanding knowledge gaps in expression durability and age-related BBB alterations. Together, these insights chart a path for engineering mRNA-LNP therapeutics capable of meeting the rising burden of neurodegenerative diseases in an ageing global population.},
}

@article {pmid42713279,
year = {2026},
author = {Kassubek, J and Müller, HP},
title = {Magnetic resonance imaging applications to amyotrophic lateral sclerosis beyond the central nervous system.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1849783},
pmid = {42713279},
issn = {1664-2295},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging ; *Magnetic Resonance Imaging/methods ; },
abstract = {Traditionally, in amyotrophic lateral sclerosis (ALS) and other motor neuron disorders, the diagnostic and research focus in the domain of magnetic resonance imaging (MRI) has been targeted on the brain and spinal cord. Nevertheless, structures outside the central nervous system (CNS) are core structures of the pathological processes and are also assessible by imaging approaches. Advanced imaging of structures like bodyfat and muscles can considerably contribute to the pathophysiological understanding and disease monitoring of ALS. The multiparametric combination of MRI approaches that capture these changes could be very helpful in future studies, especially when machine learning algorithms are used. This review summarizes the current state of the art and the role of imaging beyond the CNS in ALS, examining its diagnostic and monitoring potential and how it might ultimately lead to improved management strategies for patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging
*Magnetic Resonance Imaging/methods

@article {pmid42713950,
year = {2026},
author = {Bernard, ME and Harrison, I},
title = {Dynamically biased microcanonical treatment of HCl dissociative chemisorption on Au(111) yields thermal associative desorption dynamics by detailed balance.},
journal = {The Journal of chemical physics},
volume = {165},
number = {10},
pages = {},
doi = {10.1063/5.0345352},
pmid = {42713950},
issn = {1089-7690},
abstract = {A dynamically biased microcanonical transition state theory model of HCl dissociative chemisorption on Au(111) was recently developed for Shirhatti et al.'s [J. Phys. Chem. Lett. 7, 1346 (2016)] non-equilibrium supersonic molecular beam experiments where normal translational energies varied over a 50-250 kJ/mol range. Model parameters include a relatively low threshold energy for reaction, E0 = 30.88 kJ/mol; an efficiency, εn = 0.26, for molecular normal translational energy to contribute to the active exchangeable energy capable of promoting reaction; and one surface oscillator, s = 1, involved in the local gas-surface collision complex wherein energy was taken as microcanonically exchangeable, although potentially subject to dynamical bias through efficiencies. To validate the model, detailed balance was used to predict the desorbing HCl product state distributions from thermal associative desorption of H(c) + Cl(c) on Au(111) that have been measured by Rettner and Auerbach [Science 263, 365 (1994)] while impinging a H atom beam onto a chlorinated Au(111) surface. Modeling of Rettner's [J. Chem. Phys. 101, 1529 (1994)] rovibrationally resolved HCl product state distributions allowed for the additional establishment of a rotational efficiency of εr = 0.23 that led to consistent prediction of both the thermal associative desorption and the supersonic molecular beam experimental results. The HCl(g) ⇄ H(c) + Cl(c) reactivity on Au(111) is thereby identified as a new benchmark system for gas-surface reactivity where highly detailed experimental data are available coming from both sides of the reaction barrier. The activation energy for thermal associative desorption was estimated as Ea,assoc = 5.6 ± 1.3 kJ/mol based on four independent kinds of measurement. The effect of dynamics on the thermal dissociative sticking coefficient, S(T), of interest in practical catalysis, was quantitatively assessed. As compared to a statistically behaving HCl/Au(111) system with Ea = 31 kJ/mol, dynamics reduced S(T) by a factor of 10 at 800 K, equivalent to an increase in activation energy of ΔEa = 15 kJ/mol.},
}

@article {pmid42716035,
year = {2026},
author = {Hardiman, O},
title = {HIMALAYA: learning from another negative phase 2 trial in ALS.},
journal = {The Lancet. Neurology},
volume = {25},
number = {10},
pages = {875-877},
doi = {10.1016/S1474-4422(26)00318-2},
pmid = {42716035},
issn = {1474-4465},
}

@article {pmid42716044,
year = {2026},
author = {Cudkowicz, ME and Shefner, J and van den Berg, LH and Chio, A and Fan, D and Großkreutz, J and Lunetta, C and Tsai, RM and Li, Y and Wallstroem, E and Xiong, L and Chen, Y and Atassi, N and , },
title = {Safety, tolerability, and efficacy of RIPK1 inhibitor, SAR443820, in amyotrophic lateral sclerosis (HIMALAYA): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.},
journal = {The Lancet. Neurology},
volume = {25},
number = {10},
pages = {900-910},
doi = {10.1016/S1474-4422(26)00277-2},
pmid = {42716044},
issn = {1474-4465},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; Double-Blind Method ; Middle Aged ; Male ; Female ; Aged ; Adult ; Aged, 80 and over ; Young Adult ; Treatment Outcome ; Adolescent ; },
abstract = {BACKGROUND: RIPK1, a protein regulating inflammatory signalling and cell death, is implicated in amyotrophic lateral sclerosis (ALS) pathophysiology. SAR443820 is a selective, oral, CNS-penetrant, reversible RIPK1 inhibitor. We aimed to evaluate the safety, tolerability, and efficacy of SAR443820 in participants with ALS.

METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 2 trial was conducted at 63 clinical sites in 13 countries (Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Poland, Spain, Sweden, the UK, and the USA). Adults (aged 18-80 years) with a diagnosis of possible ALS, clinically probable ALS, clinically probable laboratory-supported ALS, or clinically definite ALS, in accordance with the revised El Escorial World Federation of Neurology criteria, were randomly assigned (2:1) by use of a stratified block design (blocks of three) to receive either 20 mg SAR443820 orally twice per day or matching placebo in the 24-week double-blind period. Randomisation was done centrally using interactive response technology and stratified by geographical region of trial site, region of ALS onset, use of riluzole, use of edaravone, and use of the combination of sodium phenylbutyrate and taurursodiol. Participants, care providers, investigators, and outcomes assessors were masked to trial intervention. The primary outcome was a change in ALS Functional Rating Scale Revised (ALSFRS-R) total score from baseline to week 24 and was calculated for all participants who had an ALSFRS-R total score available at baseline and at week 24. Safety analyses included all randomly assigned participants receiving one dose or more of trial intervention. This trial is registered with ClinicalTrials.gov (NCT05237284) and was terminated early.

FINDINGS: Between April 13, 2022, and July 17, 2023, 397 participants were screened and 305 randomly assigned to SAR443820 (n=203) or placebo (n=102); six were excluded from the primary analysis due to missing baseline ALSFRS-R values. Mean age was 56·9 years (SD 11·5); 183 (60%) participants were male and 122 (40%) were female. Least squares mean change in ALSFRS-R from baseline to week 24 was -6·73 (95% CI -7·48 to -5·98) for SAR443820 group (n=169) and -6·32 (-7·36 to -5·27) for placebo group (n=87). There was no statistically significant difference between the study groups (least squares mean difference -0·41 [95% CI -1·71 to 0·88]). Participants in the SAR443820 group had higher incidence of adverse events (171 [85%] of 202 vs placebo 80 [78%] of 102) and treatment discontinuations (28 [14%] of 202 vs placebo five [5%] of 102), with elevated hepatic enzymes being the most common cause. Nine deaths occurred in the double-blind period (seven [3%] of 202 in the SAR443820 group and two [2%] of 102 in the placebo group); none was attributed to SAR443820.

INTERPRETATION: SAR443820 did not show clinical benefit and was associated with higher hepatic enzyme increase, indicating that further clinical development of SAR443820 in ALS is not warranted.

FUNDING: Sanofi.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
Double-Blind Method
Middle Aged
Male
Female
Aged
Adult
Aged, 80 and over
Young Adult
Treatment Outcome
Adolescent

@article {pmid42716045,
year = {2026},
author = {Teunissen, CE and Vermunt, L and Barthélemy, NR and Benzinger, TLS and Graff-Radford, J and Verberk, IMW and Zetterberg, H and Schindler, SE and Jack, CR},
title = {Fluid biomarkers in the evolving care landscape of Alzheimer's disease and related disorders.},
journal = {The Lancet. Neurology},
volume = {25},
number = {10},
pages = {926-938},
doi = {10.1016/S1474-4422(26)00246-2},
pmid = {42716045},
issn = {1474-4465},
mesh = {Humans ; *Biomarkers/cerebrospinal fluid/blood ; *Alzheimer Disease/cerebrospinal fluid/diagnosis/blood ; tau Proteins/cerebrospinal fluid ; Animals ; },
abstract = {Fluid biomarkers for Alzheimer's disease have advanced rapidly during the past several years driven by breakthroughs including development of ultrasensitive and multiplexing technologies and high specificity antibodies. Blood-based biomarkers, such as neurofilament light for frontotemporal dementia and amyotrophic lateral sclerosis, and phosphorylated tau 217 for the diagnosis of Alzheimer's disease, are now being implemented in clinical practice, which is particularly timely because of the increasing clinical availability of amyloid-targeting treatments in Alzheimer's disease. Multiple fluid biomarkers are needed to capture the complexity of disease mechanisms for precise diagnosis and to measure the diverse pathologies that lead to dementia, such as vascular, α-synuclein, and TDP-43 pathologies. Moreover, fluid biomarkers can aid in capturing heterogeneity in treatment course between patients, probably due to copathologies or key intermediates, including microglia and astrocyte dysregulation. Increased focus on biomarker-pathology relationships in experimental models will likely accelerate biomarker development and further the understanding of their precise substrates. Future clinical implementation of biomarkers to capture the full complexity of pathologies will likely be facilitated by the expansion of diagnostic methods, development of point of care technologies, and remote sampling approaches.},
}

Humans
*Biomarkers/cerebrospinal fluid/blood
*Alzheimer Disease/cerebrospinal fluid/diagnosis/blood
tau Proteins/cerebrospinal fluid
Animals

@article {pmid42716967,
year = {2026},
author = {Mansour, SS and Mahmoud, AM and Moustafa, AA and Nashat, NW},
title = {"Green spectrophotometric determination of rupatadine, its toxic impurity, and methyl paraben: comparative AI-assisted univariate versus multivariate chemometrics".},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42716967},
issn = {2045-2322},
mesh = {*Parabens/analysis ; *Cyproheptadine/analogs & derivatives/analysis/chemistry ; Loratadine/analogs & derivatives/analysis ; Multivariate Analysis ; *Artificial Intelligence ; *Drug Contamination ; Spectrophotometry, Ultraviolet/methods ; Spectrophotometry/methods ; },
abstract = {Sensitive and selective green UV-spectrophotometric univariate and multivariate chemometric methods were developed to resolve the overlapped spectra of rupatadine fumarate (RUP), its impurity desloratadine (DES), and methyl paraben (MP). The univariate approach employed was the dual-wavelength (DW) method. Guided by artificial intelligence (AI) in the selection of the optimal wavelength pair, the determination of RUP was performed at 230 and 284.3 nm, and for MP at 236.6 and 253.8 nm. Among the multivariate methods, ANN demonstrated superior predictive accuracy (lowest RMSEP values), followed by PLS-1 and MCR-ALS, highlighting the power of machine learning for complex mixture resolution, particularly in the presence of the preservative MP. A three-factor, five-level experimental design was adopted to construct a calibration set comprising 25 mixtures with varying component ratios, along with 6 independent validation mixtures. The developed methods were successfully applied to pharmaceutical formulation containing the studied drug and were validated in accordance with International Conference of Harmonization (ICH) guidelines. The results obtained were reliable and reproducible, confirming the suitability of these methods for routine analysis and quality control in laboratories. Moreover, the GLANCE tool (Graphical Layout for Analytical Chemistry Evaluation) offered a clear visual summary of the twelve structured method attributes.},
}

*Parabens/analysis
*Cyproheptadine/analogs & derivatives/analysis/chemistry
Loratadine/analogs & derivatives/analysis
Multivariate Analysis
*Artificial Intelligence
*Drug Contamination
Spectrophotometry, Ultraviolet/methods
Spectrophotometry/methods

@article {pmid42717683,
year = {2026},
author = {Moody, L and Christoforidou, E and Joilin, G and Dilley, A and Hafezparast, M},
title = {Dysregulated microRNA-mRNA networks in SOD1G93A mouse skeletal muscle reveal metabolic impairments in ALS.},
journal = {Disease models & mechanisms},
volume = {},
number = {},
pages = {},
doi = {10.1242/dmm.052963},
pmid = {42717683},
issn = {1754-8411},
support = {Hafezparast/Oct19/897-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; Hafezparast/Apr21/880-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; //Sussex Neuroscience PhD Programme/ ; DOD/14/30-PF12794//My Name'5 Doddie Foundation/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multi-system disease in which skeletal muscle actively contributes to pathology, yet the regulatory circuits that drive muscle dysfunction remain unclear. We examined microRNA (miRNA)-messenger RNA (mRNA) interactions in the gastrocnemius of hSOD1G93A mice across presymptomatic, early- and late-symptomatic stages, using RNA-seq, bioinformatics, and RT-qPCR. Compared with hSOD1WT and non-transgenic controls, hSOD1G93A muscle showed mutation-specific transcriptome reprogramming: 48 dysregulated miRNAs and 558 mRNAs at presymptomatic, and 64 miRNAs and 685 mRNAs at late-symptomatic stages. Functional enrichment pinpointed carbohydrate-handling pathways (glycolysis/gluconeogenesis, pentose-phosphate, fructose-mannose metabolism) as the dominant downregulated gene sets. Network analysis revealed clusters in which upregulated miRNAs converged on, and showed inverse expression patterns relative to metabolic transcripts. RT-qPCR confirmed inverse expression of 10 candidate miRNAs and 11 metabolic mRNAs, substantiating miRNA-guided repression of glycolytic enzymes and energy-sensing nodes. Collectively, we show that SOD1G93A drives an early, sustained miRNA signature that dampens glycolysis gene expression, which could promote the fast-to-slow fibre-type transition and exacerbate energy deficit in ALS muscle. Targeting these circuits offers a strategy to restore metabolic balance and slow disease progression.},
}

@article {pmid42717824,
year = {2026},
author = {Zarco-Martín, MT and Andreo-López, MC and Yagui-Beltrán, MS and Fernández-Soto, ML},
title = {Appendicular Skeletal Muscle Mass and Sarcopenia as Prognostic Markers in Amyotrophic Lateral Sclerosis.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {17},
number = {5},
pages = {e70378},
doi = {10.1002/jcsm.70378},
pmid = {42717824},
issn = {2190-6009},
support = {2024 Award for the Best Clinical Nutrition Research Project//Sociedad Española de Nutrición Clínica y Metabolismo/ ; 74-2022//Granada Biosanitary Research Institute (Ibs. Granada)/ ; },
mesh = {Humans ; *Sarcopenia/etiology/diagnosis/mortality/pathology ; *Amyotrophic Lateral Sclerosis/complications/mortality/diagnosis ; Female ; Prognosis ; *Muscle, Skeletal/pathology/physiopathology ; Male ; Aged ; Biomarkers ; Middle Aged ; Prospective Studies ; Hand Strength ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by progressive muscle wasting and functional decline. Prognostic assessment in clinical practice relies largely on functional scales and traditional anthropometric measures. The prognostic relevance of muscle mass, muscle strength and sarcopenia in ALS remains incompletely defined. This study evaluated the prognostic value of muscle mass, muscle function and sarcopenia in relation to mortality in patients with ALS.

METHODS: A prospective observational cohort study was conducted at the ALS Multidisciplinary Unit (UMELA), San Cecilio University Hospital in Granada. Sarcopenia was defined according to the European Working Group of Sarcopenia in Older People 2 (EWGSOP2) and malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Muscle status was assessed using bioelectrical impedance vector analysis (BIVA)-derived parameters, muscle ultrasound, handgrip strength (HGS) and physical performance (SPPB). Differences between survivors and nonsurvivors were analysed and logistic regression explored potential predictors of mortality. Receiver operating characteristic (ROC) curves were constructed for significant predictors. Survival was analysed using the Kaplan-Meier and Cox proportional hazards regression.

RESULTS: A total of 42 patients with ALS were included (mean age 66.1 ± 10.3 years, and 15 (36%) were female). During follow-up (mean survival 21.1 ± 10.5 months), 45% died. Survivors showed higher appendicular skeletal muscle mass index (ASMI) (6.94 ± 0.91 vs. 5.80 ± 0.98 kg/m[2], p = 0.001), body cellular mass index (BCMI) (8.92 ± 1.59 vs. 7.64 ± 1.87 kg/m[2], p = 0.034) and HGS (25.45 ± 11.11 vs. 17.67 ± 8.83 kg, p = 0.032), while BMI did not differ (p = 0.540). Sarcopenia was more prevalent in nonsurvivors (27.8% vs. 4.8%, p = 0.047). In multivariable analysis, ASMI remained associated with mortality after adjustment for age, onset type and ALSFRS-R (OR 0.33, 95% CI 0.11-0.81, p = 0.026), but this association was not statistically significant in the fully adjusted model including disease duration (p = 0.093). ASMI showed the highest discriminative ability (AUC 0.81), compared to BCMI (AUC 0.70) and HGS (AUC 0.71). ROC-derived cut-offs (ASMI 6.74 kg/m[2]; BCMI 7.2 kg/m[2]; HGS 21 kg) stratified survival. Higher ASMI (HR 7.53, p = 0.008), BCMI (HR 4.18, p = 0.005) and HGS (HR 4.02, p = 0.019) were associated with longer survival, whereas sarcopenia increased mortality risk (HR 15.53, p < 0.001).

CONCLUSIONS: Beyond BMI, skeletal muscle mass-particularly ASMI-was associated with survival in ALS. Sarcopenia identifies a subgroup of patients at particularly high risk of death. Sarcopenia assessment may improve prognostic stratification and support clinical management in ALS.},
}

Humans
*Sarcopenia/etiology/diagnosis/mortality/pathology
*Amyotrophic Lateral Sclerosis/complications/mortality/diagnosis
Female
Prognosis
*Muscle, Skeletal/pathology/physiopathology
Male
Aged
Biomarkers
Middle Aged
Prospective Studies
Hand Strength

@article {pmid42719214,
year = {2026},
author = {Mittal, D and Solanki, P and Jain, GK and Jhawat, V and Kesharwani, P and Dutt, R and Arora, S and Singh, RP},
title = {Herbal nanoparticles in the treatment of neurodegeneration: from molecular mechanisms to therapeutic translation.},
journal = {3 Biotech},
volume = {16},
number = {10},
pages = {420},
pmid = {42719214},
issn = {2190-572X},
abstract = {UNLABELLED: Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss involving multiple pathological mechanisms, including protein aggregation, oxidative stress, neuroinflammation, and mitochondrial dysfunction. Although conventional therapies provide symptomatic relief, they fail to halt disease progression and are limited by poor blood-brain barrier (BBB) penetration, off-target effects, and systemic toxicity. Likewise, several herbal bioactives, such as curcumin, resveratrol, quercetin, and epigallocatechin gallate, exhibit promising neuroprotective properties but suffer from poor aqueous solubility, low oral bioavailability, rapid metabolism, and inadequate brain delivery. Nanotechnology-based delivery systems have emerged as a promising approach to overcome these pharmacokinetic limitations by enhancing stability, controlled release, BBB transport, and brain accumulation of herbal therapeutics. This review critically summarizes recent advances in herbal nanoformulations, emphasizing disease-specific molecular targets, BBB-targeting strategies, comparative nanocarrier systems, pharmacokinetic optimization, intracellular trafficking, and translational challenges. Unlike previous reviews, it integrates recent evidence on nanotoxicology, manufacturing scalability, quality control, regulatory considerations, and emerging technologies, including biomimetic nanoparticles and extracellular vesicles. Despite encouraging preclinical outcomes, clinical evidence remains limited, and no herbal nanoformulation has yet demonstrated definitive efficacy or received regulatory approval for neurodegenerative diseases. Future clinical translation will require standardized formulations, rigorous safety evaluation, and well-designed clinical trials. Unlike previous reviews that primarily summarize individual nanocarrier systems or herbal therapeutics, the present review provides a comprehensive and critical synthesis of the current evidence by integrating disease-specific molecular mechanisms, herbal bioactives, nanocarrier design strategies, blood-brain barrier transport mechanisms, intracellular trafficking, pharmacokinetic considerations, translational barriers, regulatory challenges, clinical evidence, and emerging technologies. Furthermore, the review identifies major knowledge gaps and future research priorities to facilitate the successful clinical translation of herbal nanoformulations for neurodegenerative disorders.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05048-8.},
}

@article {pmid42719350,
year = {2026},
author = {Imashuku, S},
title = {Literature review of pediatric Erdheim-Chester disease (ECD) and mixed histiocytosis (Langerhans cell histiocytosis/ECD).},
journal = {Annals of translational medicine},
volume = {14},
number = {4},
pages = {53},
pmid = {42719350},
issn = {2305-5839},
abstract = {BACKGROUND AND OBJECTIVE: Langerhans cell histiocytosis (LCH) and Rosai-Dorfman disease (RDD) are more commonly observed in childhood; however, Erdheim-Chester disease (ECD) predominantly affects adults, making pediatric ECD extremely rare. To find out the incidence and characteristics of ECD in children, a review article was prepared.

METHODS: A literature review was conducted to estimate the incidence of pediatric ECD and characterize its clinical features, using PubMed and Crossref, during 1990 to June 2026, with searched terms "Childhood or Pediatric", "Erdheim-Chester disease", "Mixed histiocytosis".

KEY CONTENT AND FINDINGS: A total of 28 pediatric ECD cases were collected, which compared with previously reported pediatric ECD case series (Pegoraro et al., n=21; Romano et al., n=16). Based on these reports, it was estimated that more than 30 pediatric ECD cases have been described to date. Pediatric ECD appears to be characterized by relatively high rates of central nervous system involvement (53-67%) and mixed histiocytosis (20-38%). In addition, ophthalmologic involvements in the Yeager et al.'s study in 45% (adult 30%) of pediatric ECD should be recognized as an important manifestation in the eyes even in children. Regarding prognosis, most pediatric patients with ECD were reported as alive with disease (AWD) at the time of publication, suggesting a more favorable outcome than that observed in adult cases.

CONCLUSIONS: Diagnosing ECD in children remains challenging; however, this rare entity should be considered in the differential diagnosis of pediatric histiocytosis, particularly in cases with central nervous system and ophthalmologic involvement.},
}

@article {pmid42719426,
year = {2026},
author = {Zambetti, E and Belli, S and Mucci, C and Greco, A},
title = {Living with Amyotrophic Lateral Sclerosis: Exploring what matters to patients and caregivers through their experiences.},
journal = {Palliative care and social practice},
volume = {20},
number = {},
pages = {26323524261474107},
pmid = {42719426},
issn = {2632-3524},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease the causes of which are not fully understood, that leads to early death. From the diagnosis, ALS significantly impacts the quality of life (QoL) for patients and their caregivers due to its unique characteristics. Both patients and their caregivers, formal and informal, increasingly feel the need to share their experiences, communicate their needs, and talk about what living with ALS entails.

OBJECTIVES: Given the few studies available in the literature on this topic, the study's aim is to explore the significance of ALS for patients and caregivers through their testimonies and to identify the collective representations and symbolic categories that influence their lives.

DESIGN AND METHODS: A total of 118 spontaneous written texts (67 produced by women) (81.752 tokens, TTR index=0.145; H% index=54.6%) collected from the web, from 67 ALS patients, 41 informal and 10 formal caregivers, were analyzed using the Emotional Text Mining (ETM) technique, with the T-Lab Software.

RESULTS: Four communication axes were identified: management of the disease (34.25%; physical vs. emotional), care (26.58%; technological vs. relational), support (21.39%; self-directed vs. social), and effort (17.78%; personal and institutional). The five clusters positioned in this factorial space relate to disease onset (12.29%), difficulties (30.78%), medical examinations (29.39%), coping strategies (14.79%), and needs (18.75%). There are differences between genders and groups.

CONCLUSION: The interpretation of the results enables an understanding of the cultural-symbolic system of ALS patients and caregivers, as well as the impact of the disease on their QoL. Through this, personalized interventions can be designed to promote resources and psychological well-being.},
}

@article {pmid42719847,
year = {2026},
author = {Tu, D and Riseman, J and Wei, Y and Ghosh, P and Raney, SG and Luke, MC and Evans, CL},
title = {Label-free quantification of topical drug permeation in skin using sparse spectral sampling stimulated Raman scattering imaging.},
journal = {Biophotonics discovery},
volume = {3},
number = {4},
pages = {043103},
pmid = {42719847},
issn = {3005-4745},
abstract = {SIGNIFICANCE: Stimulated Raman scattering (SRS) imaging has been used in evaluating topical drug product permeation. However, it has been mainly applied to a small group of active pharmaceutical ingredients (API) that have unique molecular bands which generate a prominent SRS signal against the background signal. The requirement of such unique molecular bands has been a large hurdle to generalizing SRS imaging to study a wide range of pharmaceutical molecules.

AIM: To overcome this barrier, an imaging method based on sparse spectral sampling stimulated Raman scattering (S4RS) microscopy and multivariate analysis was developed in this study.

APPROACH: Rather than relying on a single unique and strong peak, the API was specifically resolved using combined information from multiple wavenumbers across its spectrum. The workflow of applying this method to study APIs is demonstrated using metronidazole as an example. The sparse vibrational bands were first selected using Elastic-Net. Next, the metronidazole signal was unmixed from the compound signal of the skin-drug product mixture using multivariate curve resolution-alternating least squares (MCR-ALS).

RESULTS: The developed method demonstrated good capability in identifying the metronidazole signal in standard metronidazole-containing samples, including polymer films and skin samples treated with and without the drug product. This method enabled evaluation of the cutaneous pharmacokinetics (cPK) of metronidazole in ex vivo skin samples. Bioequivalence analysis was also completed for commercial drug products and laboratory-made control formulations containing metronidazole.

CONCLUSIONS: The developed method enables the study of APIs that lack a unique prominent peak, thereby bridging SRS imaging to a broader range of drug products.},
}

@article {pmid42707488,
year = {2026},
author = {Feyissa, GD},
title = {Serial Bogota bag tightening: A pragmatic advance in open abdomen management for resource-limited settings.},
journal = {World journal of gastrointestinal pharmacology and therapeutics},
volume = {17},
number = {3},
pages = {120768},
pmid = {42707488},
issn = {2150-5349},
abstract = {Open abdomen management poses unique challenges in resource-limited settings, where costly dynamic fascial traction techniques remain inaccessible. Balhara et al's prospective randomized trial published on the World J Gastrointest Pharmacol Ther introduces serial Bogota bag tightening, a bedside, negligible-cost method using urine bags and sutures, as an effective dynamic fascial traction alternative, achieving skin-to-skin distance ≤ 5 cm in 9.94 days vs 13 days in controls (P = 0.0003) and shortening hospital stays without added morbidity. This editorial appraises the study's strengths, contextualizes it against negative pressure wound therapy/mesh systems, and advocates its scalability for low- and middle-income countries, urging multicenter validation of long-term fascial closure.},
}

@article {pmid42707600,
year = {2026},
author = {Zhang, Z and Lu, Y and Yang, J and Li, M and Yang, M and Xu, Y and Ullah, MS and Wan, Q and Bao, B and Yu, W and Liu, X},
title = {Neurotoxic mechanisms of cadmium in neurodegenerative diseases.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1899381},
pmid = {42707600},
issn = {2296-634X},
abstract = {Cadmium (Cd) is a highly toxic, bioaccumulative heavy metal increasingly implicated in the pathogenesis of neurodegenerative disorders. This review systemically characterizes the molecular mechanisms underlying Cd-induced neurotoxicity, with particular emphasis on oxidative stress-mediated pathways that initiate interconnected processes including ferroptosis, mitochondrial impairment, disruption of calcium homeostasis, and chronic neuroinflammation. Evidence indicates that Cd exerts both convergent and disease-specific effects in neurodegenerative conditions. In Alzheimer's disease (AD), Cd exposure has been associated with enhanced amyloid-β (Aβ) deposition and increased tau hyperphosphorylation. In Parkinson's disease (PD), Cd disrupts metabolic homeostasis via the gut-liver-brain axis and promotes aberrant conformational changes and aggregation of α-synuclein (α-Syn). Within the amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) spectrum, Cd contributes to TDP-43 proteinopathy and impairs nucleocytoplasmic transport mechanisms. Therapeutic strategies targeting Cd-induced neurotoxicity are also explored, including upstream approaches like metal chelation and downstream interventions aimed at restoring autophagic flux, modulating the neuroimmune microenvironment, and enhancing neuronal repair. Although emerging platforms such as brain organoids provide valuable mechanistic insights, translating findings from in vitro models to real-world chronic exposure scenarios remains a significant challenge. This review provides a comprehensive framework for the development of early-warning systems and precision-based interventions for Cd-related neurodegeneration.},
}

@article {pmid42708447,
year = {2026},
author = {Gazal, NG and Castellanos-Montiel, MJ and Bruno, G and Franco-Flores, AK and Lépine, S and Gursu, L and Haghi, G and Maussion, G and Reintsch, WE and Stefani, FD and Anastasía, A and Bisbal, M and Gorostiza, EA and Durcan, TM and Unsain, N},
title = {BetaII-spectrin gaps and patches emerge from the patterned assembly of the actin/spectrin membrane skeleton in human motor neuron axons.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {42708447},
issn = {2050-084X},
support = {ANPCyT-PICT-2021-GRF-II-00048//Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación/ ; IBRO-Collaboration Grants 2021//International Brain Research Organization/ ; },
mesh = {Humans ; *Spectrin/metabolism ; *Motor Neurons/metabolism ; *Axons/metabolism ; *Actins/metabolism ; Induced Pluripotent Stem Cells/metabolism ; *Cytoskeleton/metabolism ; },
abstract = {The actin/spectrin membrane-associated periodic skeleton (MPS) is a cytoskeletal structure that supports axonal integrity and function. Lower spinal motor neurons (MNs) are characterized by exceptionally long axons and are particularly susceptible to degeneration in a wide range of hereditary neuromuscular disorders, including amyotrophic lateral sclerosis. Using confocal and super-resolution imaging, we characterized the spatial distribution of βII-spectrin and the assembly pattern of the MPS in human MN axons derived from induced pluripotent stem cells. We discovered a striking gap-and-patch pattern in the medial axon, where sharply demarcated βII-spectrin gaps alternate with patches containing a well-organized MPS. The pattern is acutely induced by the kinase inhibitor staurosporine and pharmacological inhibition of actin polymerization prevents patch formation, indicating a requirement for actin nucleation in MPS assembly. Our data supports a model in which spectrin incorporation into nascent MPS patches depletes neighboring regions, producing long-range gaps-and-patches patterns.},
}

Humans
*Spectrin/metabolism
*Motor Neurons/metabolism
*Axons/metabolism
*Actins/metabolism
Induced Pluripotent Stem Cells/metabolism
*Cytoskeleton/metabolism

@article {pmid42709165,
year = {2026},
author = {Hamzeh, LH and Seyed, E and Elgendy, MA and Heib, D and Sadek, BI and Mohammed, COS and El Refaei, K and Soliman, YF and Eldmrdash, N and Abdelgalil, MS and Elsayed, MM},
title = {Efficacy and safety of memantine in adults with amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42709165},
issn = {1435-1463},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited disease-modifying treatment options. Memantine, an N-methyl-D-aspartate receptor antagonist, has been investigated in ALS, but its safety remains unclear. This study systematically assessed the safety of memantine in adults with ALS. A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines, searching PubMed, Cochrane Library, Scopus, and Web of Science for randomized controlled trials of memantine in adults with ALS. Outcomes included ALSFRS-R and FVC decline, adverse neurological events, total and serious adverse events, treatment discontinuation, and all-cause mortality. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Because of heterogeneous reporting and missing variance estimates, ALSFRS-R and FVC outcomes were synthesized narratively; only safety outcomes were pooled quantitatively. Three randomized controlled trials (706 participants) met the inclusion criteria. Functional and respiratory outcomes could not be pooled because of heterogeneous reporting, and no consistent benefit was observed. Memantine showed lower headache incidence than placebo (RR 0.43; 95% CI 0.19-0.96), with no significant differences in constipation, falls, dizziness, treatment discontinuation, or all-cause mortality. Memantine showed a borderline increase in serious adverse events (RR 1.52; 95% CI 1.00-2.31) and a higher risk of total adverse events (RR 1.19; 95% CI 1.09-1.30). Memantine was associated with a small but significant increase in total adverse events and a trend toward more serious adverse events, without improving functional decline, respiratory function, or survival in ALS. Current evidence does not support its use as a disease-modifying or adjunctive therapy. Trial registration: PROSPERO CRD420261277874.},
}

@article {pmid42709218,
year = {2026},
author = {Sewell-Green, AR and Capstick, R and Holdom, CJ and Matthews-Rensch, K and Cameron, J and McCombe, PA and Henderson, RD and Ngo, ST and Steyn, FJ},
title = {Early weight loss predicts poorer prognosis and highlights limitations of predictive energy equations in amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {273},
number = {10},
pages = {},
pmid = {42709218},
issn = {1432-1459},
support = {2016-32//Wesley Medical Research/ ; CRG2025_01395//FightMND/ ; Higher Degree Research Scholarship//University of Queensland/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/metabolism ; *Weight Loss/physiology ; Prognosis ; Female ; Male ; Middle Aged ; Case-Control Studies ; Prospective Studies ; Aged ; *Energy Intake/physiology ; },
abstract = {BACKGROUND: Weight loss and malnutrition are associated with poorer outcomes in people living with amyotrophic lateral sclerosis (plwALS). This study investigated the prognostic relevance of early weight loss in plwALS and assessed whether existing energy equations provide useful guidance for nutritional management.

METHODS: In this prospective case-control and within-case comparison study (March 2016October 2024), 170 plwALS and 173 non-neurodegenerative disease controls completed baseline anthropometric and metabolic assessment. Participants with ALS were classified according to weight change during the first six months following study inclusion as Weight Gain, Stable Weight, or Weight Loss. Weight-change groups were compared for subsequent changes in anthropometry, functional capacity, and survival. In a nested cohort of 82 plwALS with reported energy intake and repeat assessments, we assessed whether the relationship between reported intake and equation-derived energy requirements was concordant with subsequent weight change.

RESULTS: Early weight loss was associated with continued loss of body weight, fat mass, and fat-free mass, faster functional decline, and increased risk of earlier death relative to Weight Gain (HR=4.78 [95% CI 2.68-8.53], p<0.001). Concordance between equation-derived energy requirements, reported energy intake and observed weight trajectory was low (17.3-32.1%). The IBW30(30) equation showed the greatest concordance among participants with Weight Loss, but no equation performed consistently across weight-change groups.

CONCLUSIONS: Early weight loss identifies plwALS at increased risk of subsequent weight and body-composition loss, functional decline and earlier death. Existing energy equations proposed for use in ALS show limited concordance with observed weight trajectories, particularly when applied at a single time point. These findings support serial monitoring of nutritional risk and individualized, phenotype-informed dietetic care in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/metabolism
*Weight Loss/physiology
Prognosis
Female
Male
Middle Aged
Case-Control Studies
Prospective Studies
Aged
*Energy Intake/physiology

@article {pmid42709229,
year = {2026},
author = {Castro, J and Sá, V and Lopes, D and Alves, I and Oliveira Santos, M and de Carvalho, M},
title = {Phrenic nerve amplitude as an effort-independent prognostic biomarker of respiratory failure in amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {273},
number = {10},
pages = {},
pmid = {42709229},
issn = {1432-1459},
mesh = {Humans ; *Phrenic Nerve/physiopathology ; *Amyotrophic Lateral Sclerosis/complications/physiopathology/diagnosis ; Female ; Male ; Prognosis ; *Respiratory Insufficiency/etiology/diagnosis/physiopathology/therapy ; Nerve Conduction Studies ; Middle Aged ; Aged ; Noninvasive Ventilation ; Action Potentials/physiology ; Cohort Studies ; Biomarkers ; },
abstract = {OBJECTIVE: In amyotrophic lateral sclerosis (ALS), the effort-dependent respiratory metrics used to determine the timing of non-invasive ventilation (NIV) lose reliability as bulbar and/or cognitive impairment progresses. We tested whether the effort-independent phrenic nerve compound muscle action potential (CMAP) amplitude predicts the timing of NIV independently of forced vital capacity (FVC) and the revised ALS Functional Rating Scale (ALSFRS-R).

METHODS: Pre-registered analysis of a single-centre ALS cohort (n = 1,486) contributing 2968 serial phrenic nerve conduction studies. Amplitude was expressed as percentage of an age- and sex-predicted value (per 10% decrease), and time to NIV initiation was the primary outcome (death competing). We used cause-specific Cox models, time-dependent and bootstrap-validated discrimination, and a Bayesian joint longitudinal-survival model.

RESULTS: Lower amplitude predicted earlier NIV (adjusted hazard ratio [HR] 1.22 per 10% decrease, 95% CI 1.16-1.27; likelihood-ratio χ[2] = 77.6, p ≈ 10⁻1⁸). The association was concentrated in the first year (HR 1.31, 1.24-1.38) and attenuated thereafter. The optimism-corrected discrimination increment over the clinical model was +0.055 (0.034-0.073); below-normal amplitude approximately doubled 12-month NIV risk (62% vs 29%). In the joint model the current amplitude (HR 1.57, 1.46-1.69) and its rate of decline (HR 1.30, 1.20-1.44) were independently prognostic.

CONCLUSIONS: Phrenic nerve conduction studies, an effort-independent neurophysiological marker carried robust, near-term, incremental prognostic information for NIV beyond FVC and ALSFRS-R, establishing diaphragmatic motor amplitude as a candidate biomarker for objective respiratory prognostication in ALS. External validation and recalibration are required before clinical use.},
}

Humans
*Phrenic Nerve/physiopathology
*Amyotrophic Lateral Sclerosis/complications/physiopathology/diagnosis
Female
Male
Prognosis
*Respiratory Insufficiency/etiology/diagnosis/physiopathology/therapy
Nerve Conduction Studies
Middle Aged
Aged
Noninvasive Ventilation
Action Potentials/physiology
Cohort Studies
Biomarkers

@article {pmid42709336,
year = {2026},
author = {Colosimo, C},
title = {The Great Transatlantic Divide: The Case of Experimental Neuropharmacology.},
journal = {Clinical drug investigation},
volume = {},
number = {},
pages = {},
pmid = {42709336},
issn = {1179-1918},
abstract = {Despite substantial agreement between the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) on new drug approval in the past decades, a few new drugs for the treatment of some of the most prevalent and severe neurological disorders, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as much rarer neurogenetic disorders, were handled differently by the two regulatory agencies. The possible reasons for the differing behaviors of the FDA and EMA are several and wide-ranging, and they will be examined in this opinion-based analysis. How patients' perceptions of the complex approaches to drug approval and commercialization may create disappointment and confusion will also be reappraised.},
}

@article {pmid42709471,
year = {2026},
author = {Chin, N and Zhang, Q and Zou, J and Cheng, KC and Zheng, W and Ye, Y},
title = {Cellular modifiers of TDP-43 phase transition and cytoplasmic aggregation.},
journal = {eLife},
volume = {15},
number = {},
pages = {},
pmid = {42709471},
issn = {2050-084X},
mesh = {*DNA-Binding Proteins/metabolism/genetics/chemistry ; Humans ; *Phase Transition ; Phase Separation ; *Cytoplasm/metabolism ; Active Transport, Cell Nucleus ; *Protein Aggregates ; Cell Nucleus/metabolism ; },
abstract = {RNA-binding protein TAR DNA-binding protein 43 (TDP-43) can form liquid-like nuclear assemblies whose phase behavior is thought to influence its aggregation propensity and neurotoxic activity. The mechanisms that govern the liquid-to-solid phase transition of TDP-43 remain poorly defined. Here, we combined chemical and genome-wide genetic screens to identify cellular factors that modulate the phase behavior of an RNA-binding-defective TDP-43 mutant. Our screens uncovered multiple cellular processes, including RNA splicing, protein translation, proteostasis imbalance, and nuclear export as TDP-43 phase regulators. We also developed a semi-permeabilized cell system that partially recapitulates the TDP-43 phase transition in vitro, and showed that nuclear export inhibition reshapes the nuclear environment to favor RNA-dependent liquid-liquid phase separation (LLPS) of TDP-43, which mitigates its aggregation. Nuclear export inhibition in a brain organoid model bearing an ALS-associated mutation reduces pathogenic phospho-TDP-43 accumulation. These findings identify multiple modulators of TDP-43 phase transitions in a sensitized model system and establish a framework for further dissecting the link between nuclear transport and TDP-43 phase dynamics.},
}

*DNA-Binding Proteins/metabolism/genetics/chemistry
Humans
*Phase Transition
Phase Separation
*Cytoplasm/metabolism
Active Transport, Cell Nucleus
*Protein Aggregates
Cell Nucleus/metabolism

@article {pmid42709996,
year = {2026},
author = {Davies, BJ},
title = {The floor, not the ceiling: industry ties across the cancer ecosystem.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag208},
pmid = {42709996},
issn = {1460-2105},
abstract = {Industry financial ties to the US cancer ecosystem are everywhere. Kim et al.'s systematic review and meta-analysis finds that financial conflicts of interest exceed 50% prevalence across most oncology domains. These relationships are not always benign. A robust body of health services research, including a 2021 systematic review of 36 studies, demonstrates that 83% of analyses identify a positive association between industry payments and prescribing behavior. Even a single industry-sponsored meal costing <$20 has been linked to significantly higher odds of prescribing the promoted drug. As federal National Institute of Health (NIH) funding faces cuts, industry's role in shaping the research agenda will only expand. Current US policy responses such as the disclosure through the Sunshine Act and dollar thresholds for guideline panelists have had minimal effectiveness in curtailing the money flowing to oncologists. This editorial argues for stronger structural reforms, specifically mandatory cooling-off periods for guideline committee members modeled on existing federal ethics statutes. Disclosure alone is insufficient, and some evidence suggests it may paradoxically license conflicted behavior. Meaningful progress requires moving beyond transparency toward policies that prevent conflicts from influencing clinical decision making.},
}

@article {pmid42710492,
year = {2026},
author = {Kage, F and Lee, M and Bramhe, S and McEwen, AG and Alpy, F and Higgs, HN},
title = {Phosphorylation-dependent interaction between VAP proteins and INF2 influences ER morphology.},
journal = {Current biology : CB},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cub.2026.08.031},
pmid = {42710492},
issn = {1879-0445},
abstract = {The endoplasmic reticulum (ER) interacts with virtually all other cellular organelles, and major players mediating these interactions are the ER-bound VAMP-associated protein (VAP) proteins VAPA and VAPB. Here, we show that VAP proteins interact with the actin polymerization factor INF2 in a phosphorylation-dependent manner. Similar to many other VAP-interacting proteins (the "VAPome"), an FFAT motif in INF2's C terminus interacts with the major sperm protein (MSP) domain of VAPs. Phosphorylation of a serine within the FFAT (S1100 in mouse; S1077 in human INF2) is necessary for high-affinity interaction both in cells and with purified proteins. The position of this phosphoserine, at position -1 of the FFAT consensus, is novel to the VAPome. Biochemical assays show that the phospho-FFAT binds both VAPA and VAPB, but not the related VAP family protein MOSPD2. Increased cytoplasmic calcium stimulates both INF2 phosphorylation and the INF2/VAP interaction. Amyotrophic lateral sclerosis (ALS)-associated mutations in the MSP disrupt the INF2/VAP interaction. Both major INF2 isoforms interact with VAPs: the INF2-CAAX isoform, which is constitutively ER-bound, and the INF2-nonCAAX isoform, which is predominantly cytosolic. For INF2-nonCAAX, VAP proteins cause ER recruitment in a phosphorylation-dependent manner. Disruption of INF2/VAP binding does not affect INF2-mediated actin polymerization but has a clear effect on ER morphology, causing the tubule/sheet balance to shift toward sheets. Cross-species evaluation suggests that only INF2 from placental mammals possesses an FFAT. These results suggest that interaction between VAP proteins and the actin polymerization factor INF2 plays a role in mediating ER morphology.},
}

@article {pmid42710553,
year = {2026},
author = {Babu, D and Le, TH and Liu, H and Raji, D and Tran, NH and Lockhart, S and Tran, P and Eldalal, O and Tonoyan, L and Siraki, AG},
title = {Edaravone as an antioxidant adjuvant to attenuate clozapine toxicity in vitro.},
journal = {Toxicology letters},
volume = {},
number = {},
pages = {113188},
doi = {10.1016/j.toxlet.2026.113188},
pmid = {42710553},
issn = {1879-3169},
abstract = {Despite being the gold-standard therapy for treatment-resistant schizophrenia, clozapine use remains constrained by the risk of rare but serious adverse drug reactions, including severe neutropenia and agranulocytosis. Neutrophil myeloperoxidase (MPO)-mediated bioactivation of clozapine to reactive metabolites has long been implicated in agranulocytosis. Although clozapine is metabolized by MPO, there are numerous other compounds that can also be metabolized by this enzyme. Edaravone is a drug used to treat amyotrophic lateral sclerosis and has potent antioxidant activity; we have previously shown that edaravone is metabolized by MPO. Therefore, we hypothesized that edaravone can attenuate early toxicological events associated with clozapine through MPO modulation. Using purified human MPO, MPO-rich human promyelocytic leukemia (HL-60) cells, and isolated human neutrophils, we evaluated clozapine oxidation, competitive intracellular uptake, protein adduct formation, and cytotoxicity. UV-visible spectroscopy demonstrated concentration-dependent inhibition of MPO-catalyzed clozapine oxidation by edaravone, with 100µM edaravone producing suppression comparable to 100µM 4-aminobenzoic acid hydrazide. LC-MS analysis showed that MPO/H2O2 reduced clozapine levels to 26.7 ± 2.9% of control, whereas co-incubation with edaravone preserved clozapine to 67.9 ± 16.2%. Under the same conditions, edaravone was almost completely consumed (0.03 ± 0.02% remaining), consistent with its sacrificial antioxidant activity. In HL-60 cells, edaravone attenuated MPO activity and did not significantly alter clozapine uptake after 30minutes (97.2 ± 7.6% of clozapine alone). Immunoblotting revealed that edaravone reduced clozapine-protein adduct formation in purified MPO, HL-60 cells, and neutrophils. Clozapine (75µM) induced marked HL-60 cytotoxicity after 24hours, whereas edaravone concentration-dependently restored viability, with 200µM fully preventing toxicity. These findings provide proof-of-concept that edaravone mitigates multiple mechanistic events linked to clozapine-induced hematological toxicity and may represent a potential strategy to improve clozapine safety.},
}

@article {pmid42710846,
year = {2026},
author = {Cunha, TA and Dourado, LC and Santana, GC and Yanagiura, MT and Galvão-Lima, LJ and Vale, SHL and Brandão-Neto, J and Dourado-Junior, MET and Leite-Lais, L},
title = {Evaluation of a self-administered version of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {9},
pages = {1-7},
doi = {10.1055/s-0046-1827063},
pmid = {42710846},
issn = {1678-4227},
support = {88887.824483/2023-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; Reproducibility of Results ; Prospective Studies ; Female ; Middle Aged ; Male ; Severity of Illness Index ; Observer Variation ; Feasibility Studies ; Aged ; *Disability Evaluation ; Adult ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) is a standard tool for evaluating functional decline in patients with ALS. Despite its clinical value, administration by healthcare professionals can be time-consuming and resource intensive.

OBJECTIVE: To assess the reliability and feasibility of a self-administration version of the ALSFRS-R as an alternative for use in clinical and research settings.

METHODS: The present was an observational, analytical, prospective, single-center study involving ALS patients followed at the Neurology Outpatient Clinic of the Hospital Universitário Onofre Lopes (HUOL). Three independent assessments of the ALSFRS-R were conducted: one self-administered version and two interviewer-administered versions performed by different researchers during face-to-face consultations. Interrater reliability was assessed using intraclass correlation coefficients (ICCs), and agreement among the three versions was analyzed using Bland-Altman plots.

RESULTS: A total of 43 participants were included in the study, with a mean age of 57 ± 11.67 years. The ICCs indicated high reliability for both the total ALSFRS-R score and its functional domains. Linear regression analyses demonstrated strong agreement between the two researchers (R[2] = 0.98, p < 0.001), as well as between each researcher and the self-administered version (R[2] = 0.90 and 0.88, respectively). Bland-Altman analyses showed minimal bias and acceptable limits of agreement across all comparisons.

CONCLUSION: The self-administered version of the ALSFRS-R demonstrated high reliability and strong agreement with the researcher-administered versions, supporting its potential use for remote monitoring of ALS patients. Nonetheless, it should not replace professional assessments in clinical trial settings. Further research is warranted to validate its applicability in broader clinical contexts and diverse patient populations.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology
Reproducibility of Results
Prospective Studies
Female
Middle Aged
Male
Severity of Illness Index
Observer Variation
Feasibility Studies
Aged
*Disability Evaluation
Adult
Surveys and Questionnaires

@article {pmid42711836,
year = {2026},
author = {Nischal, SA and Kale, KM and Tourigny, K and Abuelem, M and Greene, G and Walsh, R and Molnár, Z},
title = {Neuroanatomy education through the years: Revisiting the teaching slides used by Sir Wilfrid Edward Le Gros Clark.},
journal = {Journal of anatomy},
volume = {},
number = {},
pages = {},
doi = {10.1111/joa.70235},
pmid = {42711836},
issn = {1469-7580},
support = {//Wellcome Trust History of Neuroscience Grant/ ; //Federation of European Neuroscience Societies History of Science Grants/ ; MR/W029073/1/MRC_/Medical Research Council/United Kingdom ; BB/X008711/1//BBSRC/ ; },
abstract = {Sir Wilfrid Edward Le Gros Clark (1895-1971) was a pioneering British anatomist, physician, and evolutionary biologist whose legacy spans the foundational development of twentieth century neuroanatomy, primate biology, and medical education. From his formative experiences as a young medical officer in the First World War to his later academic ascendancy at the University of Oxford, Le Gros Clark exemplified a rare fusion of clinical insight, anatomical precision, and philosophical curiosity. His tenure in Borneo, where he studied primates in their natural habitats, enriched his evolutionary perspective, while his later role in debunking the Piltdown Man fraud cemented his place as a steadfast defender of scientific integrity. At Oxford, Le Gros Clark assembled a singular collection of neuroanatomical teaching specimens, many of which remain preserved today within the Department of Physiology, Anatomy & Genetics, University of Oxford. Through detailed analysis of selected slides, including cases of tabes dorsalis, disseminated sclerosis, amyotrophic lateral sclerosis, syringomyelia, and the pineal gland's nervus conarii, we reflect on how Le Gros Clark's anatomical interpretations anticipated many of the concepts central to contemporary neuroscience, and on how his legacy has influenced generations of students and scientists. What emerges from these materials is that Le Gros Clark taught students not simply to memorize, but to observe, interpret, and understand the functional significance of anatomical structures in health and disease.},
}

@article {pmid42712067,
year = {2026},
author = {Baeza Robba, MJ and De Oliveira, G and Oropeza, T and Iriarte, E and Cianelli, R and Kim, K and De Santis, JP},
title = {"Support us, so we can rise": A qualitative exploration of Latinas' expectations of healthcare providers after intimate partner violence.},
journal = {Women's health (London, England)},
volume = {22},
number = {},
pages = {17455057261478478},
pmid = {42712067},
issn = {1745-5065},
mesh = {Humans ; Female ; *Hispanic or Latino/psychology ; *Intimate Partner Violence/psychology/ethnology ; Qualitative Research ; Adult ; *Survivors/psychology ; *Health Personnel/psychology ; *Help-Seeking Behavior ; *Patient Acceptance of Health Care/psychology ; Middle Aged ; Social Support ; Surveys and Questionnaires ; },
abstract = {BackgroundDue to multilevel factors, it is estimated that fewer than half of Latinas in the U.S who experience Intimate Partner Violence (IPV) access the resources they need. However, among those who do seek help, approximately 35% turn to a clinic or health center. This positions front-line healthcare providers (HCPs) as key actors in mitigating barriers to care. Delivering survivor-centered care, however, requires a nuanced understanding of Latina survivors' expectations of HCPs, grounded in their lived experiences and the structural contexts that shape their lives.ObjectivesThis study aimed to explore Latina survivors' expectations of healthcare providers during IPV disclosure and help-seeking.DesignA qualitative descriptive study guided by Liang et al.'s help-seeking theory.MethodsTwenty-five Latina IPV survivors living in South Florida were purposively recruited. Data collection included socio-demographic questionnaires and in-depth interviews (23 in Spanish, 2 in English/mixed). Interviews were transcribed and analyzed thematically in English by bilingual researchers. This study adheres to the SRQR Checklist.ResultsParticipants shared five key themes under the overarching concept "Support us, so we can rise", including 1) direct assessment, "If you ask us, we are going to tell"; 2) non-judgmental listening, "Create a supportive space"; 3) proactive referral and follow-up; 4) tailored support systems and social services; 5) delivery of educational interventions. Culturally responsive, empowering, and sustained provider engagement were seen as essential to fostering disclosure, resilience, and recovery.ConclusionFuture research should prioritize healthcare provider-led interventions and educational strategies that foster trust, safety, and empowerment while also facilitating a sustained help-seeking process. This includes proactive referrals and a thoughtful balance between follow-up care and respect for the survivor's autonomy. Incorporating a culturally specific perspective is critical to addressing the evolving needs of this population and advancing equity in care delivery.},
}

Humans
Female
*Hispanic or Latino/psychology
*Intimate Partner Violence/psychology/ethnology
Qualitative Research
Adult
*Survivors/psychology
*Health Personnel/psychology
*Help-Seeking Behavior
*Patient Acceptance of Health Care/psychology
Middle Aged
Social Support
Surveys and Questionnaires

@article {pmid42712181,
year = {2026},
author = {Mohajerin, B and Howard, R and Pincus, AL},
title = {A Response to Dimaggio et al.'s Commentary on Mohajerin et al. (2026).},
journal = {Clinical psychology & psychotherapy},
volume = {33},
number = {5},
pages = {e70332},
doi = {10.1002/cpp.70332},
pmid = {42712181},
issn = {1099-0879},
mesh = {Humans ; *Psychotherapy/methods ; Randomized Controlled Trials as Topic ; },
abstract = {Our randomized controlled trial comparing Unified Protocol (UP) and Schema-Focused Therapy (SFT) for grandiose and vulnerable presentations of narcissism has recently been critiqued in a commentary by Dimaggio et al. (2026). These authors raised concerns regarding the study's recruitment and subgroup classification, gender distribution, treatment response patterns, absence of dropouts, randomization, screening and recruitment procedures, trial registration, outcome assessment, supervision and treatment fidelity, treatment dose and duration, and disclosure of the NPD diagnosis. In this response, we clarify these methodological and procedural issues and provide additional information that was not fully described in the original article. We maintain that while both treatments were effective in ameliorating symptoms of narcissism, SFT was more effective in treating grandiose features, while UP was more effective in treating vulnerable features. Trial Registration: Iranian Registry of Clinical Trials identifier: IRCT20231106059970N3.},
}

Humans
*Psychotherapy/methods
Randomized Controlled Trials as Topic

@article {pmid42701950,
year = {2026},
author = {Morgillo, F and Digennaro, V and Panciera, A and Benvenuti, L and Carbone, N and Ferri, R and Zielli, SO and Faldini, C},
title = {Torsional deformities and anterior knee pain: a systematic review and clinical approach to miserable malalignment syndrome.},
journal = {Musculoskeletal surgery},
volume = {},
number = {},
pages = {},
pmid = {42701950},
issn = {2035-5114},
abstract = {Despite advancements in understanding and treating anterior knee pain linked to lower limb torsional deformities, a definitive consensus on diagnostic criteria, clinical indications, and therapeutic strategies for "miserable malalignment syndrome" remains elusive. This systematic review synthesizes current research to unify understanding of this complex condition. Findings highlight varied definitions and surgical approaches, underscoring standardization challenges. This systematic review aimed to synthesize current research to provide a more unified understanding of this complex condition. While studies report favorable anatomical correction and symptomatic relief, inconsistent clinical outcome scores and limited long-term follow-up hinder robust comparisons. Conservative measures are often ineffective due to underlying mechanical imbalance; surgical interventions, primarily derotational osteotomies of the femur and/or tibia, offer the most direct anatomical correction. However, optimal level, extent, and timing of these osteotomies-whether single or double level, staged or simultaneous-are debated. Liße et al.'s proposed diagnostic criteria offer a valuable step towards standardized identification of true miserable malalignment syndrome. Future research, particularly robust multi-center studies with standardized outcome measures, is critically needed to establish clearer, evidence-based guidelines, ultimately improving patient care and long-term outcomes for this challenging condition.},
}

@article {pmid42702895,
year = {2026},
author = {Uysal, SP and Dudley, KA and Sullivan, S and Brizzi, KT and Burke, KM and Hall, S and Pease, K and Goldstein, JN and Berry, JD and Ho, DT},
title = {Emergencies in Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70398},
pmid = {42702895},
issn = {1097-4598},
abstract = {Emergencies are frequent in people living with amyotrophic lateral sclerosis (pALS), especially as the disease progresses, and can necessitate urgent evaluation and intervention. Progressive weakness in ALS inevitably increases fall risk, making discussion of fall prevention strategies integral to caring for pALS. Thromboembolic events and respiratory failure may present insidiously in ALS, requiring a high index of clinical suspicion, and management strategies differ from those for individuals without ALS. Bulbar impairment in ALS can give rise to aspiration, laryngospasm, and malnutrition leading to emergency department (ED) visits, underscoring the need for early consideration of gastrostomy tube placement. PALS face an increased risk of serious infections, making vigilant monitoring for any acute change essential. Tracheostomy and gastrostomy, although life-sustaining measures in ALS, may require ED care when complications arise. Proactive assessment and management are critical to prevent complications related to constipation, urinary dysfunction, cognitive and behavioral issues. Although serious adverse events from ALS treatments are very rare, potential immune-mediated neurologic complications are a consideration with tofersen use. Importantly, ALS emergencies should be viewed as potential indicators of disease progression, prompting timely serious illness discussions and reassessment of goals of care. Anticipation of potential complications and emergencies, combined with an understanding of appropriate evaluation and evidence-based management, constitute critical components of caring for pALS. Early recognition and proactive management of these emergencies can improve safety, reduce avoidable hospitalizations, and support goal-concordant, patient-centered care.},
}

@article {pmid42703939,
year = {2026},
author = {Sun, J and Vocht, J and Laroy, M and Stam, D and Lien, CH and Lamaire, N and D'Hondt, A and Peeters, R and Sunaert, S and Van Damme, P and Vandenbulcke, M and Van den Stock, J},
title = {Tracking Socio-emotional Brain Changes in Premanifest C9orf72 Repeat Expansion Carriers: A Structural and Functional 2-Year Longitudinal Magnetic Resonance Imaging Study.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78355},
pmid = {42703939},
issn = {1531-8249},
support = {//Foundation Thierry Latran/ ; //Alzheimer Research Foundation/ ; //Sequoia Fund for Research on Ageing and Mental Health/ ; 12AQF24N//FWO-Vlaanderen/ ; G0C0319N//FWO-Vlaanderen/ ; G030025N//FWO-Vlaanderen/ ; G019625N//FWO-Vlaanderen/ ; //KU Leuven,/ ; C24/18/095//KU Leuven Research Council/ ; C24/18/095; IDN/21/010//KU Leuven Research Council/ ; J1990130-233837//King Baudouin Foundation/ ; },
abstract = {OBJECTIVES: The C9orf72 hexanucleotide repeat expansion (C9RE) is the most frequent genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. Although structural alterations have been reported decades before symptom onset, the longitudinal evolution of socioemotional network dysfunction in premanifest C9RE carriers remains poorly understood.

METHODS: In this multimodal 2-year longitudinal study, we examined 21 premanifest C9RE carriers and 24 controls using structural magnetic resonance imaging (MRI), resting-state, and task-based functional MRI (fMRI), and multivariate pattern analysis. Participants completed facial emotion processing tasks during fMRI scanning, alongside behavioral assessments. We assessed regional activation, network connectivity, and voxel-wise structural integrity at baseline and follow up.

RESULTS: At baseline, premanifest C9RE carriers showed reduced emotion recognition efficiency, accompanied by bilateral thalamic atrophy, decreased activation in the anterior and posterior cingulate cortex, and increased activation in the posterior cerebellum, along with altered multivoxel activity patterns in the anterior cingulate and posterior cerebellum. Resting-state fMRI revealed decreased functional connectivity involving the thalamus, anterior, and posterior cingulate cortex. Longitudinal analyses indicated declining emotion-evoked responses in the posterior cingulate cortex and cerebellum, alongside further thalamic volume loss, whereas functional connectivity showed no significant change over time. Despite these progressive neural alterations, behavioral performance remained stable.

INTERPRETATION: Socioemotional circuit dysfunction emerges early in C9RE carriers and progresses over time, preceding overt clinical symptoms. Functional imaging, especially task-based fMRI combined with multivariate pattern analysis, captures early circuit-level alterations that may serve as sensitive biomarkers for premanifest neurodegeneration. ANN NEUROL 2026.},
}

@article {pmid42704422,
year = {2026},
author = {Demir, BS and Cicek, SO and Houran, MA and Azizoglu, ZB and Asan, M and Bas, H and Cetin, BS and Gumus, H and Erdem, S and Canatan, H and Unal, E and Hsieh, EW and Kısaarslan, AP and Eken, A},
title = {Clinical and immunological characterization of a child with a homozygous TBK1 kinase-domain truncation.},
journal = {Immunologic research},
volume = {74},
number = {1},
pages = {},
pmid = {42704422},
issn = {1559-0755},
support = {TSG-2023-10935 and TYG-2023-13110//Erciyes University Research Council (BAP Grants)/ ; },
mesh = {Humans ; *Protein Serine-Threonine Kinases/genetics/metabolism ; Homozygote ; *Arthritis, Juvenile/genetics/immunology/diagnosis ; *Encephalitis/genetics/immunology ; Cytokines/metabolism ; Mutation/genetics ; Phosphorylation ; Female ; Male ; Child ; },
abstract = {TBK1 is a serine-tyrosine kinase protein that transmits signals from pattern recognition receptors to the NF-κB pathway leading to production of Type 1 Interferons. Mutations in this protein have been associated with arthritis, vasculitis, herpes simplex encephalitis and amyotrophic lateral sclerosis. In the current study, we characterized the functional consequences of a TBK1-variant bearing a truncation in exon 4 and 5 in a patient with poly arthritis resembling juvenile idiopathic arthritis and necrotizing encephalitis. The truncation was associated with reduced TBK1 protein abundance and altered phosphorylation. The variant was associated with increased basal/and or Poly-I: C induced IL-6, TNFα, IL-1β and IL-18 and type 1 Interferon ex vivo. Our findings expand the phenotypic spectrum of TBK1 loss-of-function variants and may provide insight into the management of immune dysregulation in affected patients.},
}

Humans
*Protein Serine-Threonine Kinases/genetics/metabolism
Homozygote
*Arthritis, Juvenile/genetics/immunology/diagnosis
*Encephalitis/genetics/immunology
Cytokines/metabolism
Mutation/genetics
Phosphorylation
Female
Male
Child

@article {pmid42705614,
year = {2026},
author = {Fritsch, J and Wiesner, S and Guthmann, F and Richter, MF},
title = {[Pulmonale Hämorrhagie bei Frühgeborenen <1000 g (ELBW): Risikofaktoren und präventive Maßnahmen als Reaktion auf eine gestiegene Inzidenz].},
journal = {Klinische Padiatrie},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2954-5687},
pmid = {42705614},
issn = {1439-3824},
}

@article {pmid42705992,
year = {2026},
author = {Nie, W and Jing, Z and Cheng, L and Li, LL and Bai, Y and Xu, F and Li, S and Lin, L and Dong, X and Yu, L and Cai, L and Pan, B and Han, H and Cheng, H and Wang, X},
title = {ROMO1 loss in cholinergic neurons induces mitochondrial ultrastructural damage and ALS-like neuromuscular degeneration.},
journal = {Science bulletin},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.scib.2026.08.063},
pmid = {42705992},
issn = {2095-9281},
}

@article {pmid42706741,
year = {2026},
author = {Grouls, A and Ubel, PA and Nguyen, M and Pathapati, N and Doerstling, S and Sloan, CE},
title = {Online Crowdfunding Campaigns for People Living With ALS Demonstrate Financial Burden and Unmet Needs.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70395},
pmid = {42706741},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: People living with amyotrophic lateral sclerosis (ALS; pALS) have extensive care needs, from wheelchairs to feeding tubes to caregiving support. The financial impact of these needs on pALS and their caregivers (cALS) has not been fully explored. We aimed to explore the types of expenses for which pALS and cALS crowdfund, and the financial circumstances that lead them to resort to crowdfunding.

METHODS: We randomly selected 320 ALS-related crowdfunding campaigns posted on the GoFundMe platform from 2010-2020. We conducted a summative content analysis to categorize the expenses for which campaigns requested money and descriptions of financial burden.

RESULTS: We included 266 campaigns. Most campaigns were written by people who were not the pALS or cALS, such as children or coworkers (85.3%). Most campaigns fundraised for medication and treatment costs (21.4%), equipment (25.2%), accessibility needs for home (24.0%), and transportation (19.5%), and in-home caregiving services (18%). Multiple campaigns (22.9%) requested assistance with nonmedical expenses ranging from rent and utilities to personal travel and hobby goals. Many campaign writers (47.7%) described financial burden related to the pALS' diagnosis, including medical debt (4.5%) and job loss of the pALS (30.5%) and/or cALS (6.8%).

DISCUSSION: Our analysis of ALS-related crowdfunding campaigns highlights the breadth of medical and nonmedical care needs and quality of life goals for which people request additional financial support throughout the disease course. These findings provide important insights for ALS care teams into the expenses of pALS.},
}

@article {pmid42706758,
year = {2026},
author = {Zumbo, BD},
title = {Conditional Standard Error of Measurement as an Estimand of Individual Score Precision: Remarks on Pfadt et al. from an Operator-Theoretic Perspective.},
journal = {Psychometrika},
volume = {},
number = {},
pages = {1-7},
doi = {10.1017/psy.2026.10141},
pmid = {42706758},
issn = {1860-0980},
abstract = {This commentary supports Pfadt et al.'s (2026, Psychometrika, 2026, 1-35. https://doi.org/10.1017/psy.2026.10081) recommendation that individual score interpretation should rely on conditional standard errors of measurement rather than a single unconditional standard error. I argue, however, that this recommendation requires a sharper test-theoretic formulation. Conditional precision is not merely a computational refinement of the standard error of measurement; it is a different estimand, defined by the information structure relative to which score precision is interpreted. Using an operator-theoretic formulation of classical test theory, I treat the true score as a conditional expectation, the error score as a projection residual, and the standard error of measurement as the norm of that residual. From this perspective, conditional standard errors localize residual variation with respect to observed scores, score bands, persons, trait levels, or measurement contexts. This formulation clarifies why assumptions associated with particular estimation procedures should not be attributed to classical test theory itself, and why practices such as pooling sparse score groups change the estimand. The commentary concludes that responsible individual score interpretation requires identifying the relevant conditional-precision estimand before selecting an estimator or software procedure.},
}

@article {pmid42707250,
year = {2026},
author = {Unuakhalu, R and Purcell, A and Jindal, I and Wu, Y and Arnold, M and Dominick, KC and Shillington, A},
title = {The long road to diagnosis: recessive PMPCB deficiency hidden behind a dominant familial VCP defect.},
journal = {Molecular genetics and metabolism reports},
volume = {48},
number = {},
pages = {101350},
pmid = {42707250},
issn = {2214-4269},
abstract = {Multiple mitochondrial dysfunctions syndrome 6 (MMDS6), caused by biallelic likely pathogenic variants in PMPCB, is an extremely rare autosomal recessive childhood-onset neurodegenerative disorder, with only six reported cases to date, most resulting in early mortality. Pathogenic variants in VCP cause multisystem proteinopathy 1 (MSP1), an autosomal dominant adult-onset disorder encompassing inclusion body myopathy (IBM), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), typically presenting in mid-adulthood. We describe a 23-year-old female with two likely pathogenic variants presumed to be in trans in PMPCB and a co-occurring pathogenic VCP variant. She was misdiagnosed for over 20 years with early-onset VCP-related neurodegeneration due to a maternal family history of ALS. Her disease began at birth with microcephaly and progressed throughout childhood, including developmental regression, cerebellar and cerebral atrophy, optic atrophy, seizures, spasticity, dysarthria, and loss of ambulation. Initial genetic testing identified only the familial VCP variant. Updated genomic sequencing at age 23 revealed two likely pathogenic PMPCB variants, strong supporting a diagnosis of MMDS6. Her clinical features closely align with previously reported MMDS6 cases and are inconsistent with the typical adult-onset phenotype of VCP-associated disorders. While she shares overlapping features with VCP-related disease (limb-girdle weakness, spasticity, FTD), the timing and severity of her neurodevelopmental findings support MMDS6 as the primary diagnosis. Early mitochondrial dysfunction may predispose her to an accelerated or more severe future VCP-associated phenotype. This is the first report of combined likely pathogenic and pathogenic variants in PMPCB and VCP respectively, expanding the phenotypic spectrum of both disorders. The case underscores the necessity of periodic re-evaluation with advanced genetic testing, highlights important ethical and familial implications, and informs future diagnosis and management of patients with overlapping rare genetic conditions.},
}

@article {pmid42696637,
year = {2026},
author = {Guarino, AS and Wallace, J and Rohan, AM and Kroelinger, CD},
title = {Implementation Outcomes of 36 CDC-funded Statewide Perinatal Quality Collaboratives, 2023-2024.},
journal = {Journal of public health management and practice : JPHMP},
volume = {},
number = {},
pages = {},
pmid = {42696637},
issn = {1550-5022},
abstract = {CONTEXT: Maternal and infant morbidity and mortality remain high in the United States, and improving quality of clinical care is one strategy to improve outcomes. Perinatal Quality Collaboratives (PQCs) are statewide networks of teams working to improve maternal and infant health by supporting quality improvement (QI) initiatives. PQCs execute deliberate activities to support implementation of QI; implementation outcomes can be used to measure the execution of these activities.

OBJECTIVE: To examine PQC implementation outcomes to better understand implementation achievements.

DESIGN: We adapted Proctor et al.'s implementation outcomes framework to measure implementation outcomes using standardized annual PQC performance measures.

SETTING: US, October 2023 through September 2024.

PARTICIPANTS: Thirty-six Centers for Disease Control and Prevention-supported PQCs.

INTERVENTION: Developed implementation outcome definitions relevant for the standard PQC programmatic model and mapped outcomes to performance measures, assessing the execution of PQC activities. Descriptive PQC-reported data were summarized as counts and percentages.

MAIN OUTCOME MEASURE: Implementation outcomes (adoption, appropriateness, feasibility, fidelity, penetration, and sustainability).

RESULTS: PQCs reported moderate adoption, with an average of 67% of births in a state occurring in birthing hospitals that participated in PQC QI initiatives. PQCs also reported moderate appropriateness; among birthing hospitals serving populations most likely to experience adverse health outcomes, 67% participated with their PQC. An average of 85% of participating birthing hospitals submitted data to their PQC as required for QI initiatives (feasibility), and PQCs averaged 75% or higher on all fidelity measures (trainings, webinars, learning products, and convenings). For penetration, fewer than 50% of PQCs engaged in activities with community-based organizations, although 56% engaged with community members and 83% with patients/families. Most (78%) participating hospitals made lasting system changes (sustainability).

CONCLUSIONS: Findings suggest that PQCs implement QI initiatives with high feasibility, fidelity, and sustainability, moderate adoption and appropriateness, and varied penetration. Understanding PQC implementation outcomes can highlight areas of success and identify areas for PQC improvement.},
}

@article {pmid42697152,
year = {2026},
author = {Fernández-Beltrán, LC and García-Toledo, I and Javaloyes García, K and Jiménez-Coca, I and Jiménez-Rodríguez, J and Fernández-Bernal, A and Godoy-Corchuelo, JM and Portero-Otín, M and Corrochano, S},
title = {Pharmacological modulation with the LXR agonist T0901317 attenuates motor pathology in the SOD1[G93A] mouse model of ALS.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e01062},
doi = {10.1016/j.neurot.2026.e01062},
pmid = {42697152},
issn = {1878-7479},
abstract = {Dysregulation of cholesterol metabolism and neuroinflammation are critical drivers of Amyotrophic Lateral Sclerosis (ALS) pathology. Liver X receptors (LXRs) are master regulators of cholesterol homeostasis and immune responses. Here, we evaluated the therapeutic potential of chronic pharmacological modulation using the potent synthetic agonist T0901317 (T0) in the hSOD1[G93A] mouse model. To assess both long-term functional outcomes and the underlying molecular mechanisms, T0 was administered via two distinct experimental designs. In a longitudinal cohort treated from postnatal day 60 (P60) until the humane endpoint, T0-treated SOD1G93A mice exhibited delayed body weight loss and sustained improvements in neuromuscular strength and motor coordination. Critically, this continuous treatment preserved functional motor unit connectivity, delayed overall clinical progression, and significantly extended median lifespan. While protective in both sexes, the survival benefit was slightly more pronounced in females. Molecular characterization revealed that the early systemic T0 administration successfully engaged canonical LXR targets in the spinal cord, driving a significant transcriptional upregulation of cholesterol efflux pathways and suppressing pro-inflammatory signaling cascades. This response induced a lipid partitioning, evidenced by a significant accumulation of cholesterol esters within the central nervous system, potentially mitigating lipotoxicity. Taken together, these findings demonstrate that T0901317 treatment exerts a significant beneficial effect, highlighting the pharmacological modulation of these lipid and inflammatory networks as a promising therapeutic strategy for ALS.},
}

@article {pmid42697153,
year = {2026},
author = {Lo'pez-Blanch, R and Salvador-Palmer, R and Oriol-Caballo, M and Moreno-Murciano, P and Dellinger, RW and Estrela, JM and Obrador, E},
title = {Corrigendum to 'Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice'.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e01070},
doi = {10.1016/j.neurot.2026.e01070},
pmid = {42697153},
issn = {1878-7479},
}

@article {pmid42697379,
year = {2026},
author = {Mohammad, SI and Vasudevan, A and Oriquat, G and Gajjar, TB and Hanumanthayya, M and Shukla, SK and Tailor, NK and Baig, MR and Fadaam, O and Abdul, AS},
title = {Extracellular Vesicles in Neurodegenerative Diseases: A New Frontier in Diagnosis and Therapy.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116455},
doi = {10.1016/j.bbr.2026.116455},
pmid = {42697379},
issn = {1872-7549},
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are among the progressive disorders of the nervous system that are characterized by the gradual destruction of neurons, the accumulation of misfolded proteins, and the limited effective therapeutic options. In recent years, numerous lines of evidence have emphasized the important role of extracellular vesicles (EVs) in the formation and progression of these diseases. These vesicles are membrane-bound nanoscale structures that are secreted by almost all cell types and play a role in cell-cell communication through the transfer of molecules such as proteins, lipids, and nucleic acids. In neurodegenerative disorders, EVs can facilitate the transport and dissemination of disease-related proteins, including amyloid-β, tau, α-synuclein, mutant huntingtin, SOD1, and TDP-43, thus contributing to the spread of pathological processes in different parts of the nervous system. On the other hand, the ability of these vesicles to cross the blood-brain barrier and reflect molecular changes occurring in the central nervous system makes them valuable candidates for the development of minimally invasive biomarkers. This review reviews the biogenesis, classification, isolation methods, and molecular content of EVs, and analyzes their role in the pathogenesis, diagnosis, and treatment of the most important neurodegenerative diseases. Also, the importance of EV-associated proteins, RNAs, and lipids as emerging diagnostic biomarkers, as well as the therapeutic potential of natural and engineered vesicles as drug delivery systems and regulators of neuroinflammation and neurodegenerative processes, is discussed.},
}

@article {pmid42697520,
year = {2026},
author = {Sharma, A and Jatana, N},
title = {Microbiota-derived metabolite-GPCR signalling in neurodegeneration.},
journal = {Neuroscience},
volume = {615},
number = {},
pages = {312-333},
doi = {10.1016/j.neuroscience.2026.09.001},
pmid = {42697520},
issn = {1873-7544},
abstract = {The gut microbiome acts as a primary regulator of host homeostasis, influencing the entire body through bidirectional communication along the gut-brain axis (GBA). Dysbiosis, which is defined as a state of microbial imbalance involving alterations in community composition and function, can disrupt the synthesis of important microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), bile acids and neurotransmitter precursors. This can lead to impaired essential host signalling pathways. There is growing evidence that metabolic alterations associated with dysbiosis contribute to the onset and progression of neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). In this context, G protein-coupled receptors (GPCRs) act as essential molecular transducers that link microbial metabolites to intracellular signalling networks. Aberrant GPCR activation, driven by altered metabolite profiles, modulates key downstream pathways including cAMP, MAPK, PI3K/Akt, NF-κB and Ca2 + signalling. This promotes neuroinflammation, oxidative stress, mitochondrial dysfunction and pathological protein aggregation - hallmark processes underlying neurodegeneration. By identifying convergent and disease-specific signalling pathways, the review highlights mechanistic nodes of therapeutic relevance and discusses GPCR-centric emerging and other microbiome-targeted strategies aimed at restoring metabolic and signalling homeostasis in neurodegenerative disorders.},
}

@article {pmid42697669,
year = {2026},
author = {Zhang, P and Liu, Y and Tian, X and Wang, H and Liu, R and Wang, G and Wu, Y},
title = {Overexpression of the cytochrome P450 gene CYP99A3 likely mediates mesosulfuron-methyl resistance in Lolium multiflorum from China.},
journal = {Pesticide biochemistry and physiology},
volume = {223},
number = {},
pages = {107300},
doi = {10.1016/j.pestbp.2026.107300},
pmid = {42697669},
issn = {1095-9939},
mesh = {*Lolium/genetics/drug effects/enzymology/metabolism ; *Sulfonylurea Compounds/pharmacology ; *Cytochrome P-450 Enzyme System/genetics/metabolism ; *Herbicide Resistance/genetics ; *Herbicides/pharmacology ; China ; *Plant Proteins/genetics/metabolism ; Acetolactate Synthase/genetics ; },
abstract = {Lolium multiflorum L. (Italian ryegrass) is a noxious weed causing severe yield losses in wheat production globally, and its rapid expansion across major wheat-producing regions in China poses an escalating agricultural threat. Recently, field-recommended doses of the acetolactate synthase (ALS) inhibitor mesosulfuron-methyl have failed to effectively control certain L. multiflorum populations. This study evaluated the resistance level and elucidated the underlying mechanisms in a suspected mesosulfuron-methyl-resistant L. multiflorum population (ZMHF-R) collected from China. Whole-plant bioassays demonstrated that the ZMHF-R population exhibited a high level of resistance (43.34-fold) to mesosulfuron-methyl. Replicate sequencing of the ALS gene revealed no known target-site mutations, thereby excluding target-site mutation-mediated resistance. Pretreatment with the cytochrome P450 inhibitors piperonyl butoxide (PBO) and malathion significantly synergized mesosulfuron-methyl toxicity in ZMHF-R, implicating P450 monooxygenases in the resistance phenotype. Comparative RNA-seq and RT-qPCR validation identified the constitutive overexpression of a specific P450 gene, LmCYP99A3, in the R population. Molecular docking simulations predicted favorable binding and potential metabolic activity of the LmCYP99A3 protein toward mesosulfuron-methyl. Furthermore, transgenic rice calli heterologously overexpressing LmCYP99A3 exhibited a distinct resistance phenotype against the herbicide. Taken together, this study functionally validates that LmCYP99A3 mediates mesosulfuron-methyl resistance in L. multiflorum, expanding our understanding of the metabolic basis of NTSR in this global weed species.},
}

*Lolium/genetics/drug effects/enzymology/metabolism
*Sulfonylurea Compounds/pharmacology
*Cytochrome P-450 Enzyme System/genetics/metabolism
*Herbicide Resistance/genetics
*Herbicides/pharmacology
China
*Plant Proteins/genetics/metabolism
Acetolactate Synthase/genetics

@article {pmid42698124,
year = {2026},
author = {Streicher, NS},
title = {Serum Neurofilament Light Chain and GFAP in Amyotrophic Lateral Sclerosis on a Commercial ECLIA Platform.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70397},
pmid = {42698124},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: In amyotrophic lateral sclerosis (ALS), SIMOA-based studies show that baseline serum neurofilament light chain (NfL) predicts the revised ALS Functional Rating Scale (ALSFRS-R) decline rate and survival. The Roche Elecsys electrochemiluminescence immunoassay (ECLIA) reports values approximately six-fold lower; cross-platform comparison confirms comparable performance, but serial clinical-practice data remain limited. We assessed whether ECLIA NfL correlates with the ALSFRS-R decline rate under the sampling conditions of clinical practice, and whether GFAP or S-100B adds prognostic or disease-specific information.

METHODS: We retrospectively analyzed 58 patients with medical-record-confirmed ALS at an academic center (2022-2026). Serum NfL, GFAP, and S-100B were measured on the Roche Elecsys ECLIA. The NfL-ALSFRS-R correlation was assessed within matching windows; serial NfL was examined in patients with repeat draws.

RESULTS: First-per-patient NfL median was 7.06 pg/mL (IQR 4.06-17.30). NfL correlated strongly with the ALSFRS-R decline rate (Spearman r = 0.704, n = 31; r = 0.809 within 90 days, n = 17; both p < 0.0001). Fast progressors had 3.7-fold higher mean NfL than slow progressors (17.10 vs. 4.64 pg/mL). NfL showed no correlation with King's clinical stage (r = 0.00). GFAP correlated with age but not with progression rate or disease duration; S-100B showed no association with progression.

DISCUSSION: Serum NfL on a commercial ECLIA platform retained its strong correlation with progression rate despite unstructured sampling, replicating SIMOA-based findings at platform-specific values. NfL tracked the rate of decline rather than the accumulated disease state; GFAP and S-100B added no prognostic or disease-specific information.},
}

@article {pmid42698179,
year = {2026},
author = {Dhar, A and Sharar, AD and Papisetty, S and Bydon, M and Moinuddin, FM},
title = {The Therapeutic Potential of Purmorphamine Across Disease Models.},
journal = {Journal of cellular and molecular medicine},
volume = {30},
number = {17},
pages = {e71349},
pmid = {42698179},
issn = {1582-4934},
mesh = {Humans ; Animals ; *Purines/therapeutic use/pharmacology ; Signal Transduction/drug effects ; Hedgehog Proteins/metabolism ; Disease Models, Animal ; Neuroprotective Agents/pharmacology/therapeutic use ; Morpholines ; },
abstract = {Purmorphamine (PUR) is a trisubstituted purine compound that selectively activates Smoothened receptor, thereby initiating Sonic Hedgehog (Shh) signalling-a pathway critical for embryonic patterning, neuronal specification and tissue regeneration across multiple organ systems. Dysregulation of Shh signalling has been implicated in degenerative diseases yet therapeutic interventions targeting this pathway remain limited. PUR demonstrates broad therapeutic efficacy across diverse preclinical disease models by activating both canonical GLI-mediated transcription and non-canonical Shh pathways, resulting in neuroprotection, reduced neuroinflammation, enhanced blood-brain barrier integrity and tissue regeneration. In contrast to previous assumptions that Shh pathway activation requires endogenous ligand binding, PUR bypasses this requirement through direct Smoothened engagement, offering a pharmacologically tractable approach to pathway modulation. Preclinical studies demonstrate that PUR enhances motor neuron survival in amyotrophic lateral sclerosis models, protects dopaminergic neurons in Parkinson's disease, reverses behavioural abnormalities in autism spectrum disorder, promotes neurovascular repair following stroke, restores myelin integrity in multiple sclerosis models and drives osteogenic differentiation in bone tissue engineering applications. Beyond its established Smoothened agonist activity, recent evidence identifies PUR as a positive allosteric modulator of the secretin receptor, expanding its therapeutic scope to include cardiovascular applications such as hypertension management through enhanced nitric oxide bioavailability.},
}

Humans
Animals
*Purines/therapeutic use/pharmacology
Signal Transduction/drug effects
Hedgehog Proteins/metabolism
Disease Models, Animal
Neuroprotective Agents/pharmacology/therapeutic use
Morpholines

@article {pmid42698276,
year = {2026},
author = {Strong, MJ and Donison, N and Al-Chalabi, A and Boeve, B and Finger, EC and Holstege, H and Huey, ED and Lee, EB and Marzi, SJ and McHutchison, C and McMillan, CT and Otto, M and Petrucelli, L and Prudencio, M and Simuni, T and Tartaglia, MC and Turner, MR and Van Damme, P and Wolk, DA},
title = {Progress towards a biotypic biomarker profile for amyotrophic lateral sclerosis-frontotemporal spectrum disorders.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag297},
pmid = {42698276},
issn = {1460-2156},
abstract = {Determining the optimal timing of disease-modifying therapies for neurodegenerative disorders will necessitate identification of when the underlying pathobiological process becomes active, well in advance of the point at which clinical manifestions appear. Phenoconversion, the emergence of clinically manifest syndomes, may be preceded by years to decades of silent pathobiological activity that can only be mapped by an array of biomarkers. ALS and FTD, traditionally identified as distinct clinical syndromes, are increasingly recognized to exist along a spectrum of clinical syndromes with shared genetic risk and shared underlying pathology. This clinicopathological spectrum is underpinned by cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43) as the common neuropathological hallmark. In contrast, the majority of neuropathologically-defined frontotemporal lobar degeneration (FTLD) is associated with alterations in either TDP-43 metabolism (FTLD-TDP) or of the microtubule associated protein tau (FTLD-tau), with a smaller percentage associated with either autosomal dominant genetic mutations or impairments in the ubiquitin proteasome system. As the field of neurodegenerative disorders increasingly shifts towards the frameworks of a pathobiological definition of disease, there is a growing imperative to develop biomarkers that reflect the varied pathobiologies that underly these disorders, and to determine the sensitivity of such biomarkers to detect the presence of these pathobiologies before phenoconversion. To that end, an international workshop was convened in London, Canada in 2025 to review the evidence for existing or evolving biomarkers suitable for (1) the detection of either ALS or FTD pathobiology prior to phenoconversion and/or (2) predict phenoconversion in at risk individuals. Such biomarkers might be conceptualized as "biotypic biomarkers", capturing their ability to describe an underlying pathophysiology whilst being agnostic to the emergent clinical manifestations. Whereas no single biotypic marker is yet able to predict the emergence of ALS, FTD or their intersection, a multimodal approach to developing a biotypic biomarker profile holds promise for the detection of relevant pathobiological processes. The strength of such an approach would be augmented by also addressing issues of resiliency/susceptibility both in terms of genetic risk susceptibility profiles and developing sensitive biomarkers of genomic and cellular aging. By including such nontraditional markers of disease, a more robust picture of not only the degenerative process but also of those factors that might potentially mitigate or drive a heightened probability of disease can be derived.},
}

@article {pmid42698373,
year = {2026},
author = {Pan, L and Hou, C and Seitz, C and Ingre, C and Hedman, ÅK and Laffita, J and Vu, TN and Pawitan, Y and Ullgren, A and Yazdani, S and Andersson, J and Joyce, EE and Chourpiliadis, C and Lovik, A and Chen, Y and Lewandowski, SA and Fernandez-Capetillo, O and Barz, M and Samuelsson, K and Press, R and Piehl, F and Graff, C and Mälarstig, A and Fang, F},
title = {Protein Biomarkers in Risk and Prognosis of Amyotrophic Lateral Sclerosis.},
journal = {European journal of neurology},
volume = {33},
number = {9},
pages = {e70741},
pmid = {42698373},
issn = {1468-1331},
support = {223077//Åhlen Stiftelse/ ; //Bjorklunds fund/ ; MegaALS, 802091//H2020 European Research Council/ ; //Bruno and Ilse Frick Foundation for Research on ALS/ ; FO2022-0233//Hjärnfonden/ ; 2021-01276//Karolinska Institutet/ ; //Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse/ ; F2021-0116//Neuro Sweden/ ; 2023-02428//Swedish Research Council/ ; 2021-02605//Swedish Research Council/ ; FIB-ALS//Fondation Thierry Latran/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/cerebrospinal fluid/diagnosis ; *Biomarkers/blood/cerebrospinal fluid ; Female ; Prognosis ; Male ; Middle Aged ; Aged ; },
abstract = {BACKGROUND: Plasma and cerebrospinal fluid (CSF) protein biomarkers in amyotrophic lateral sclerosis (ALS) may provide insight into disease mechanisms and yield clinically useful biomarkers.

METHODS: Overall, 363 proteins in plasma and CSF from 198 patients with ALS and 125 matched controls were profiled using Olink assays. Associations with disease status, survival, and functional decline, as well as longitudinal biomarker stability across the disease course were assessed, together with network and enrichment analyses. ALS risk-associated biomarkers were externally validated in the UK Biobank (UKB).

RESULTS: Overall, 125 proteins were significantly associated with at least one outcome (i.e., case status, risk, survival, or functional decline), and 21 were associated with three or more outcomes. NEFL was the most robust biomarker in plasma and CSF, alongside TNFRSF12A in plasma and CSF, EDA2R in plasma, and FABP4 in plasma and CSF. Most biomarkers remained stable longitudinally across the disease course. ALS risk-associated biomarkers were replicated in UKB, in which > 3000 plasma proteins were measured in 52,990 participants, including 298 with ALS. Network and enrichment analyses highlighted their roles in immune response and extracellular-matrix remodeling, and their enrichments in the brain and T-cell subsets. Construction of an ALS risk-prediction model achieved an ROC-AUC of 0.72 in the UKB validation cohort.

CONCLUSIONS: These findings suggest candidate protein biomarkers for ALS risk stratification, early detection, and clinical therapeutic monitoring.},
}

Humans
*Amyotrophic Lateral Sclerosis/blood/cerebrospinal fluid/diagnosis
*Biomarkers/blood/cerebrospinal fluid
Female
Prognosis
Male
Middle Aged
Aged

@article {pmid42699326,
year = {2026},
author = {Wang, J and Kissling, WD},
title = {LiDAR-derived dataset of extracted trees and shrubs from AHN4 airborne laser scanning in the Oostvaardersplassen wetland, the Netherlands.},
journal = {Data in brief},
volume = {68},
number = {},
pages = {113169},
pmid = {42699326},
issn = {2352-3409},
abstract = {This article describes a geospatial dataset of trees and shrubs extracted from the fourth Dutch national airborne laser scanning (ALS) survey (AHN4) covering the Oostvaardersplassen wetland in the Netherlands. The dataset was generated in the context of the MAMBO project, which focuses on automated workflows for deriving habitat condition metrics from LiDAR data for European habitat monitoring. The input data consist of nationally acquired AHN4 point clouds (2020-2022). A dedicated processing workflow was applied to classify and extract woody vegetation points in marsh and reedbed environments, where trees and shrubs co-occur with dense herbaceous vegetation. The workflow includes (i) pre-processing and segmentation of vegetation points, (ii) clustering of tree and shrub points using neighbourhood analysis and voxel-based aggregation, and (iii) delineation of individual woody elements through seed detection and connectivity analysis in three-dimensional space. Accuracy assessments were conducted using manually created ground truth datasets derived from ALS point clouds and by referencing 8 cm resolution aerial imagery for selected validation plots and patches. The dataset includes classified ALS point clouds (LAZ), extracted tree and shrub point clouds (LAZ), derived raster products (GeoTIFF), vector boundary files (ESRI Shapefile), processing scripts, and documentation. The dataset and associated processing workflow, source code, and metadata are publicly available through Zenodo, GitHub, and the LifeWatch Metadata Catalogue. The dataset can be reused for applications such as habitat structure mapping, woody vegetation monitoring in wetlands, LiDAR-based workflow benchmarking, training and validation of classification algorithms, and upscaling of tree extraction approaches to other airborne laser scanning datasets.},
}

@article {pmid42701411,
year = {2026},
author = {Gonzo, P and Dunkl, S and Gatterbauer, M and Heider, S and Girsa, M and Krammel, M and Schnaubelt, S},
title = {Structured Evaluation and Treatment of cardiac arrest via the ABCDE approach (SETA) - Rethinking high-performance CPR and cause-finding during Advanced Life Support.},
journal = {Resuscitation plus},
volume = {31},
number = {},
pages = {101458},
pmid = {42701411},
issn = {2666-5204},
abstract = {The European Resuscitation Council (ERC) Guidelines 2025 continue to summarize the causes of cardiac arrest that should be sought during advanced life support (ALS) as "4Hs and 4Ts". While well established, this list-based mnemonic does not map onto the airway-breathing-circulation-disability-exposure (ABCDE) sequence that emergency teams use for every other patient assessment, and it excludes causes that are clinically treatable but not classically "reversible" in the prehospital phase. We present SETA (Structured Evaluation and Treatment of cardiac arrest via the ABCDE approach), a concept developed within the Emergency Medical Service Vienna that restructures both cause-finding during cardiopulmonary resuscitation (CPR) and evaluation of high-performance CPR around the ABCDE sequence, embeds protocol-linked actions at each step, and is designed to run within ongoing chest compressions without interrupting them. We outline its rationale, its relationship to existing pit-crew and ABCDE-based resuscitation models, and the prospective evaluation now needed before considered for wider use.},
}

@article {pmid42701529,
year = {2026},
author = {Kadish, CB and Gage, CB and Powell, JR and Ulintz, AJ and Wang, HE and Gaw, CE and Muller, G and Panchal, AR},
title = {Practice variability of epinephrine administration in pediatric out-of-hospital cardiac arrest in the United States.},
journal = {Resuscitation plus},
volume = {31},
number = {},
pages = {101454},
pmid = {42701529},
issn = {2666-5204},
abstract = {BACKGROUND: Pediatric out-of-hospital cardiac arrests (pOHCA) are low frequency, high acuity events for Emergency Medical Services (EMS). The survival rate is low, with only 10% of children surviving, and few survivors having favorable neurologic outcomes. Optimal prehospital management of pOHCA includes rapid epinephrine administration, yet factors contributing to its administration are not well understood.

OBJECTIVE: Our study objective was to evaluate the frequency of epinephrine administration in pOHCA. Our secondary objective was to characterize the demographic and clinical characteristics associated with epinephrine administration in pediatric OHCA in the United States.

METHODS: In this retrospective, observational study, we analyzed data from the National Emergency Medical Services Information System (NEMSIS) dataset for the year 2021. We identified pediatric patients ages ≥1 day-old to <18 years-old from "9-1-1" activations that were treated by advanced life support (ALS) clinicians. OHCA events were identified by performance of cardiopulmonary resuscitation (CPR) or defibrillation. We used descriptive statistics to evaluate the frequency of epinephrine administration and assess demographic and clinical characteristics in this population. Multivariable logistic regression model was utilized to find characteristics associated with epinephrine administration.

RESULTS: In 2021, 8495 pOHCA events (median [IQR] age: 3.0 [0.3-13.0] years; 58.5% males) were managed by an ALS unit in the United States. Two out of every five (40.2%) pOHCA events did not receive epinephrine. Epinephrine use was more common in younger age groups (1 day-1 year OR, 1.25 [95% CI, 1.07-1.46]; 1-5 years OR, 1.19 [95% CI, 1.00-1.38]; 6-12 years OR, 1.59 [95% CI, 1.24-1.79]; referent: 13-17 years), urban population settings (OR, 2.06 [95% CI: 1.79-2.38]), incidents with scene time >10 min (OR, 1.41, [95% CI, 1.25-1.60]), advanced airway attempt(OR 8.33, [95% CI, 7.33-9.47]), and in those receiving defibrillation (OR 1.95, [95% CI, 1.61-2.37]). Odds of epinephrine administration were lower in public settings (OR 0.55, [95% CI, 0.47-0.65]) and in females (OR 0.83, [95% CI, 0.73-0.93]).

CONCLUSION: Epinephrine is not given in 2 of every 5 pOHCA events. Longer scene time and additional resuscitation interventions were associated with epinephrine administration. The low rate of administration has implications for further research and reforms in the prehospital care of critically ill children.},
}

@article {pmid42701881,
year = {2026},
author = {Zhu, Y and Zhang, Y and Yan, T and Li, Y and Du, H and Zhang, S and Zhang, T and Zhou, W},
title = {The Role of overdose Folic Acid in Promoting Neuroinflammation, Oxidative Stress, and Apoptosis in SOD1-G93A Mice.},
journal = {Free radical research},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/10715762.2026.2729677},
pmid = {42701881},
issn = {1029-2470},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition that involves the targeted degeneration of motor neurons. The precise pathogenetic mechanisms are still largely unclear. In this study, we utilized the SOD1-G93A mouse model of ALS to investigate the effects of folic acid (FA), an important factor involved in homocysteine metabolism. Our results indicated that a little FA prolong the lifespan of the SOD1-G93A mice and medium and high dose FA significantly shortened the lifespan of the SOD1-G93A mice. Furthermore, we observed that overdose FA significantly elevated inflammation levels in the cerebellum, as evidenced by increased concentrations of tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Cluster of Differentiation 68 (CD68), Cluster of Differentiation 86 (CD86), and Monocyte Chemoattractant Protein-1 (MCP-1), facilitating microglial activation. The low dose FA were the opposite of the overdose FA. Additionally, high dose FA increased the levels of phosphorylated p65 (p-p65)/p65, thereby promoting the NF-κB signaling pathway. Conversely, high dose FA inhibited the expression of total superoxide dismutase (T-SOD) while increasing the level of malondialdehyde (MDA) in the cerebellum; these effects were not observed in muscle tissue. Moreover, high dose FA elevated the levels of Bax2/Bcl-2. Concurrently, high dose FA induced increased apoptosis in SOD1-G93A mice, as demonstrated by TUNEL staining. Notably, the brain iron content of SOD1-G93A mice remained unchanged following FA treatment. These findings provide evidence that overdose FA supplementation may exert pro-inflammatory effects by promoting the NF-κB pathway, oxidative stress, and apoptosis in the context of ALS.},
}

@article {pmid42694267,
year = {2026},
author = {Heffernan, ÁB and Do, F and Carter, E and Al-Tameemi, F and Selvaraj, BT and Stavrou, M},
title = {Disrupted astrocyte-neuron metabolic coupling in amyotrophic lateral sclerosis.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1899307},
pmid = {42694267},
issn = {2296-634X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by progressive loss of motor neurons. In addition to neurodegeneration, ALS is increasingly recognised as a disorder associated with widespread metabolic dysfunction, including hypermetabolism, weight loss, and dyslipidaemia, all of which correlate with disease progression and survival. Astrocytes play a central role in maintaining metabolic homeostasis in the central nervous system by supporting neuronal energy demands, regulating glutamate levels, buffering oxidative stress, and maintaining lipid balance. Emerging evidence suggests that disruption of these supportive astrocytic functions may contribute directly to motor neuron vulnerability in ALS. In this mini-review, we discuss how alterations in astrocyte metabolism may impair astrocyte-neuron metabolic coupling in ALS. We summarise work from human studies and experimental models demonstrating abnormalities in astrocytic glycolysis, mitochondrial function, lactate shuttling, lipid metabolism, and glutamate homeostasis. We highlight growing evidence implicating mitochondrial dysfunction and impaired lipid handling in astrocytes as important contributors to disease progression. We explore how these changes may deprive motor neurons of metabolic and antioxidant support while also promoting excitotoxicity, oxidative stress, and lipotoxicity. We also discuss how recent advances in human induced pluripotent stem cell models, metabolomics, and single-cell transcriptomics are improving our understanding of astrocyte dysfunction in ALS. Finally, we consider current and emerging therapeutic strategies aimed at restoring astrocytic metabolic function. Together, these findings support the idea that progressive failure of astrocyte-mediated metabolic support is an important component of ALS pathogenesis and may represent a promising therapeutic target.},
}

@article {pmid42694478,
year = {2026},
author = {Cui, Q and Zheng, K and Liu, Q and Wang, L and Liu, Y and Bai, R and Zhang, W and Guo, J and Chang, X and Wang, J},
title = {From metabolism to neurodegeneration: how microglial functional reprogramming drives neurodegenerative diseases.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1921079},
pmid = {42694478},
issn = {1662-5099},
abstract = {Microglia are brain-resident myeloid cells that maintain central nervous system homeostasis and respond dynamically to neuronal injury, protein aggregation, and alterations in the local metabolic environment. Single-cell and single-nucleus studies demonstrate that microglial responses in neurodegenerative diseases are highly heterogeneous and cannot be adequately explained by the classical M1/M2 polarization model. Increasing evidence further indicates that metabolic remodeling is not merely a consequence of activation but a determinant of microglial migration, phagocytosis, inflammatory signaling, redox balance, organelle function, and interactions with surrounding neural cells. In this review, we propose a microglial immunometabolic trajectory framework in which metabolic states are viewed as branching and potentially reversible determinants of cellular function rather than fixed stages of a universal disease pathway. We summarize how glucose metabolism, mitochondrial function, lipid metabolism, amino acid metabolism, lysosomal activity, and redox regulation shape microglial plasticity. We further examine relationships among transcriptionally defined states, including disease-associated microglia, microglia associated with neurodegeneration, lipid-droplet-accumulating microglia, and other disease-enriched populations, while emphasizing that transcriptional similarity does not necessarily imply metabolic function or lineage progression. Comparative evidence from Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis indicates that common metabolic regulators, including HIF-1α, mTOR, PKM2, TREM2, APOE, and NLRP3, exert disease-specific effects with unequal mechanistic support. We further distinguish associative metabolic signatures from intervention-based causal evidence and discuss limitations of animal models, immortalized cell lines, postmortem tissue, and induced pluripotent stem cell-derived microglia. Finally, we highlight the need for cell-specific, state-resolved, and temporally precise metabolic interventions that restore defined microglial functions without compromising physiological immune surveillance.},
}

@article {pmid42694654,
year = {2026},
author = {Wu, Y and Duan, L and Zhang, L and Wang, S and Yan, H and He, M and Wang, T and Li, L and Gao, Y},
title = {TREM2 as a central hub of neuroimmune-metabolic crosstalk in central nervous system disorders: from microglial biology to therapeutic targeting.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1912989},
pmid = {42694654},
issn = {1664-3224},
mesh = {Humans ; *Microglia/metabolism/immunology ; *Receptors, Immunologic/metabolism/genetics/immunology ; *Membrane Glycoproteins/metabolism/genetics/immunology ; Animals ; *Central Nervous System Diseases/metabolism/immunology/therapy ; Signal Transduction ; *Neuroimmunomodulation ; },
abstract = {Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-enriched immunoreceptor that functions as a central regulator of microglial adaptation by integrating immune surveillance, lipid sensing, metabolic reprogramming, and phagocytic responses in the central nervous system (CNS). Through association with the adaptor protein DAP12, TREM2 activates interconnected signaling networks involving the SYK pathway, PLCγ2-mediated Ca[2+] signaling, PI3K-AKT-mTOR signaling, NF-κB activation and inflammatory regulatory pathways, thereby shaping microglial survival, migration, clearance capacity, and interactions with surrounding neural and immune cells. Increasing evidence from genetic studies, single-cell transcriptomics, spatial analyses, and human-derived microglial models indicates that TREM2 dysfunction contributes to diverse CNS disorders; however, its biological consequences are highly dependent on disease stage, pathological substrate, cellular context, and microenvironmental cues. In Alzheimer's disease, TREM2 regulates amyloid-β-associated microglial responses, lipid metabolism, and synaptic remodeling, while its effects on tau-driven neurodegeneration remain controversial. In Parkinson's disease, stroke, epilepsy, and amyotrophic lateral sclerosis, TREM2 influences α-Syn clearance, inflammatory resolution, tissue repair, and microglial state transitions, but may exert beneficial or maladaptive effects depending on temporal dynamics and disease-specific stressors. Emerging clinical evidence, including TREM2 variants, soluble TREM2 (sTREM2) biomarkers, and human multi-omics studies, highlights both the translational potential and complexity of targeting this pathway. Herein, this review summarizes the molecular mechanisms, physiological functions, and disease-specific roles of TREM2 in CNS disorders, critically discusses unresolved controversies and species-specific challenges, and evaluates emerging therapeutic strategies toward biomarker-guided and stage-specific modulation of TREM2 signaling. Understanding how to restore appropriate microglial adaptability rather than simply enhance or suppress TREM2 activity may provide a foundation for precision therapies in CNS disorders.},
}

Humans
*Microglia/metabolism/immunology
*Receptors, Immunologic/metabolism/genetics/immunology
*Membrane Glycoproteins/metabolism/genetics/immunology
Animals
*Central Nervous System Diseases/metabolism/immunology/therapy
Signal Transduction
*Neuroimmunomodulation

@article {pmid42694829,
year = {2026},
author = {Chowdhury, S and Pramanik, S and Bhattacharjee, S and Billah, M},
title = {ALSGate: An Efficient Gated Mixture-of-Experts Model for Reliable ALS Detection Using EMG Signals.},
journal = {Healthcare technology letters},
volume = {13},
number = {1},
pages = {e70097},
pmid = {42694829},
issn = {2053-3713},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons, resulting in neuromuscular weakness and paralysis. Electromyography (EMG) is of vital importance for the detection of ALS. In this paper, a refined mixture of experts is proposed that automatically discriminates ALS patients from non-ALS cases using clinical EMG signals from the N2001 EMGLAB open-access dataset. The architecture consists of a 1D convolutional neural network, a temporal convolutional network and a spectrogram-based CNN to collectively learn localised temporal, long-range temporal and spectral features from EMG activity. A gating mechanism dynamically weights expert contributions and performs significantly better than equal-weight fusion. Training with focal loss and exponential moving average stabilisation addresses class imbalance and improves convergence. The proposed approach reached an AUROC of 0.9992, an F1-score of 0.9903 and a balanced accuracy of 0.9905, demonstrating strong discriminative performance and potential for real-time clinical applications.},
}

@article {pmid42696048,
year = {2026},
author = {de Bertier, S and Amador, MD and Guissart, C and Miki, T and Boillée, S and Lobsiger, CS and Bohl, D and Fauret-Amsellem, AL and Bohic, A and , and Giguet-Valard, AG and Bellance, R and Beauvais, K and Meininger, V and Bruneteau, G and Salachas, F and Vial, C and Camu, W and Esselin, F and de la Cruz, E and Bernard, E and Seilhean, D and Millecamps, S},
title = {Familial, neuropathological and cellular analysis identify ARPP21 as a major amyotrophic lateral sclerosis associated gene in French cohorts.},
journal = {Acta neuropathologica},
volume = {152},
number = {1},
pages = {},
pmid = {42696048},
issn = {1432-0533},
support = {EQU202103012581//Fondation Recherche Médicale (FRM, France)/ ; #19466//Association Française contre les Myopathies (AFM, France)/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; France ; Female ; Male ; Middle Aged ; Cohort Studies ; Aged ; Adult ; DNA-Binding Proteins/metabolism ; *Genetic Predisposition to Disease ; Mutation/genetics ; Animals ; Brain/pathology ; },
abstract = {ARPP21 has recently emerged as a new amyotrophic lateral sclerosis (ALS) associated gene but its pathogenic role remains unclear. In this study we performed familial, clinical, neuropathological and cellular analyses to characterize the recurrent p.P529L and p.P713L variants (also known as p.P563L variant and p.P747L variant, respectively) in our French ALS cohort of 1190 ALS cases and 50 additional family members available for segregation analysis, resulting in the description of 29 ARPP21-linked patients. ARPP21 emerged as the most frequent rare ALS-associated gene in France after exclusion of the four major ALS genes, accounting for 2.7% of familial cases (fALS) and 0.1% of sporadic cases. Age-dependent penetrance reached 45% by age 50 and increased only modestly thereafter, remaining incomplete even at advanced ages. In cellular models, the p.P713L mutant showed aggregation associated with protein hyperphosphorylation and colocalization with the autophagic marker p62. Neuropathological examination of tissue from a p.P529L carrier revealed typical cytoplasmic TDP-43 pathology, together with heterogeneous ARPP21-positive deposits. As ARPP21 antibody also stained granulovacuolar degenerations, ARPP21-positive deposits may reflect neuronal stress rather than mutant ARPP21-specific pathology. Nevertheless, together with previous studies, our findings support ARPP21 as an important ALS-associated gene, and indicate that both p.P529L/p.P563L and p.P713L/p.P747L should be considered pathogenic ALS-causing variants. Incorporating ARPP21 into the routine genetic testing panels for fALS could improve diagnostic yield.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology
France
Female
Male
Middle Aged
Cohort Studies
Aged
Adult
DNA-Binding Proteins/metabolism
*Genetic Predisposition to Disease
Mutation/genetics
Animals
Brain/pathology

@article {pmid42691260,
year = {2026},
author = {Aguirre-Urreta, M and Yamini, R and Rönkkö, M},
title = {Can formative latent variables represent psychological concepts? Replication and extension of MacKenzie et al. (2005).},
journal = {The Journal of applied psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/apl0001415},
pmid = {42691260},
issn = {1939-1854},
support = {//Research Council of Finland/ ; },
abstract = {We revisit MacKenzie et al.'s (2005) influential work on bias in path estimates arising from the misspecification of formative latent variable models as reflective ones. Using simulations, we demonstrate that the bias in unstandardized path coefficients reported by MacKenzie et al. is due to scaling differences rather than model misspecification. When these differences are taken into account, the bias nearly disappears. Building on their work, we also demonstrate that the formative indicators in their model are unnecessary. This is because the formative latent variables derive their identity from the reflective indicators added for model identification. Removing one or even all formative indicators is inconsequential for estimating the paths between latent variables. Our study reveals a fundamental problem with this approach: Formative latent variables (whether first or higher order) cannot represent psychological concepts as intended because their identity derives from downstream reflective indicators rather than the formative indicators. We conclude by discussing the implications for measurement and index construction. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid42691539,
year = {2026},
author = {Hsu, EC and Carder, P and Smith, L and Zhou, ZE and Yakusheva, O and Beeber, A and Jutkowitz, E and Thomas, KS},
title = {A Profile of Assisted Living Direct Care Workforce Training Requirements Across the United States.},
journal = {Journal of the American Medical Directors Association},
volume = {27},
number = {10},
pages = {106445},
doi = {10.1016/j.jamda.2026.106445},
pmid = {42691539},
issn = {1538-9375},
abstract = {OBJECTIVES: To characterize assisted living (AL) direct care worker (DCW) training requirements across the United States and how these regulations have changed over time. Specifically, we examine state-level profiles of training regulations, including duration, frequency, content, source of materials, evaluation, and changes in regulatory coverage.

DESIGN: Cross-sectional and longitudinal descriptive study using state policy data and AL directories from 2019, 2021, and 2023.

SETTING AND PARTICIPANTS: All US states' AL training-related regulations; all ALs and AL beds governed by those regulations.

METHODS: We used a mixed-methods approach with an explanatory sequential design (QUAN → qual), first conducting health services regulatory analysis followed by qualitative content analysis.

RESULTS: In 2023, 43 states (90% of ALs, nationally) required DCW training, 29 states required annual training frequency, 28 states specified training hours (median 10 hours), 28 required dementia-specific content, and 29 required training to cover at least 5 topics when onboarding. Common training topics included resident rights, emergency response, infection control, and personal care; dementia-specific training topics included Alzheimer's disease, behavior, communication, and dignity of residents, with only 2 states requiring training that addressed DCWs' well-being. Ten states mandated use of professionally designed courses, and 5 states required DCWs to complete an exam. From 2019 to 2023, 6 states made changes to the scope of dementia-specific training.

CONCLUSIONS AND IMPLICATIONS: While most states mandate DCW training and over half require annual frequency, duration, and cover 5 topic areas, few states specify sources of training materials or require competency checks. Lack of specificity in training requirements requires AL operators to determine what constitutes adequate training for DCWs to be successful. To better prepare the AL workforce for growing resident complexity, policymakers should consider promoting specific training requirements that ensure both onboarding and continuous education for DCWs, particularly around dementia care and workforce well-being.},
}

@article {pmid42693185,
year = {2026},
author = {Dalakas, MC and Lünemann, JD},
title = {Role of complement and complement-targeted therapeutics in neurological diseases.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {42693185},
issn = {1759-4766},
abstract = {Complement comprises a group of plasma and membrane proteins that provide an effective bridging function for innate and adaptive humoral immunity. Understanding complement pathophysiology is fundamental given that inappropriate complement function in host defence can lead to infectious diseases and inefficient disposal of altered, damaged or senescent cells can lead to or enhance autoimmune neurological processes. Although the rising number of approved drugs targeting complement pathways remains primarily focused on diseases with complement-fixing pathogenic antibodies (such as myasthenia gravis and neuromyelitis optica spectrum disorder), a robust pipeline of emerging treatments holds promise for expanding complement-targeted therapies to a broader spectrum of autoimmune neurological diseases, such as multiple sclerosis and even neurodegenerative diseases such as Alzheimer disease or amyotrophic lateral sclerosis. This Review presents insights into complement biology as it relates to the development or initiation of autoimmune and possibly degenerative diseases affecting the central and peripheral nervous systems or muscle. The effects, merits, risks and challenges of marketed drugs or biologic agents in ongoing phase I-III clinical trials engineered to inhibit proximal or distal components of the complement cascade are also discussed. Anti-complement therapeutics are destined to change the treatment of autoimmune neurologic conditions in which the therapeutic landscape is now becoming crowded with biologic agents targeting other key autoimmunity factors.},
}

@article {pmid42693862,
year = {2026},
author = {Ardakani, RH and Dashtaki, M and Mohamadi-Zarch, SM and Bagheri, SM},
title = {Cortisol Dysregulation as a Major Factor in the Development of Neurodegenerative Diseases, Drug Targets and Therapeutic Prospects: A Comprehensive Review.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273466502260813092749},
pmid = {42693862},
issn = {1996-3181},
abstract = {Cortisol, regulated by the hypothalamic-pituitary-adrenal (HPA) axis, is critical for stress response, metabolism, and immune function. Its dysregulation is increasingly implicated in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). This review synthesizes evidence on cortisol's role in neurodegenerative disorders, exploring its mechanisms, clinical implications, and therapeutic potential. This study analyzed preclinical models, clinical studies, and biomarker data to elucidate cortisol's impact on neurodegeneration. Key mechanisms include glucocorticoid and mineralocorticoid receptor-mediated effects on synaptic plasticity, neuroinflammation, and oxidative stress. In AD, elevated cortisol accelerates cognitive decline, hippocampal atrophy, and amyloid-β accumulation. In PD, higher cortisol levels correlate with gait dysfunction and dopaminergic neuron loss. HD shows variable cortisol profiles, with early hypocortisolism shifting to hypercortisolism in later stages, linked to depression. In ALS, elevated cortisol hastens disease progression and neuroinflammation. In MS, HPA axis hyperactivity is associated with cognitive deficits and lesion activity, though it may support remyelination. Chronic stress exacerbates these effects across disorders, promoting neuronal vulnerability. Cortisol dysregulation is a significant contributor to neurodegenerative pathology, acting as both a biomarker and therapeutic target. Emerging interventions, including glucocorticoid receptor antagonists, cortisol synthesis inhibitors, and stress reduction strategies, show promise in mitigating neuronal damage. Personalized, stage-specific therapies and longitudinal studies are needed to optimize cortisol-targeted treatments for neurodegenerative diseases.},
}

@article {pmid42687189,
year = {2026},
author = {Keritam, O and Bormann, D and Haimberger, F and Gharib, D and Sener, M and Gruber, F and Antoniewicz, L and Fedak, I and Renner, A and Fasching, B and Ullrich, S and Paternostro, R and Dolak, W and Masel, EK and Schuhfried, O and Rath, J and Zulehner, G and Krenn, M and Zimprich, F and Cetin, H},
title = {Implementation of specialised care improves survival in patients with amyotrophic lateral sclerosis.},
journal = {Neurological research and practice},
volume = {8},
number = {1},
pages = {},
pmid = {42687189},
issn = {2524-3489},
abstract = {OBJECTIVE: Access to multidisciplinary care influences survival in patients with amyotrophic lateral sclerosis (pwALS). However, real-world data comparing structured specialised care with general neurological management remain limited. We aimed to assess the influence of implementing a specialised outpatient clinic on survival in pwALS.

METHODS: This retrospective cohort study included pwALS meeting the Gold Coast criteria who were treated at the Department of Neurology of the Medical University of Vienna between January 2009 and July 2023. Demographic and clinical parameters and survival data were obtained from the local ALS registry, the Austrian Federation of Social Insurance databases, and the national mortality database of Statistik Austria. Data were censored in December 2024. Outcomes were compared between patients managed before (general care cohort) and after the establishment of a specialised ALS outpatient clinic in 2018 (specialised care cohort).

RESULTS: A total of 242 pwALS were included (47.5% female), of whom 43.8% received general neurological care and 56.2% specialised care. Spinal onset ALS was observed in 65.1% and 70.6%, respectively. Baseline demographic and clinical characteristics were comparable between both cohorts. Median survival time was 27.0 months (95% CI 23.0-35.0) in the general care cohort and 40.0 months (95% CI 32.0-47.0) in specialised care cohort (p = 0.0173). This survival difference was driven by patients with spinal onset ALS, whereas no benefit was observed in those with bulbar onset disease.

CONCLUSIONS: Specialised care was associated with improved survival in this real-world ALS cohort, likely reflecting the cumulative effect of coordinated multidisciplinary management rather than individual interventions.},
}

@article {pmid42688548,
year = {2026},
author = {Hassell, LA and Gallati, M and Thoma, M and Asfaw, S and Hart, AC},
title = {Glutamatergic neuron degeneration in C. elegans models of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.},
journal = {microPublication biology},
volume = {2026},
number = {},
pages = {},
pmid = {42688548},
issn = {2578-9430},
support = {P40 OD010440/OD/NIH HHS/United States ; R21 NS116254/NS/NINDS NIH HHS/United States ; T32 GM149433/GM/NIGMS NIH HHS/United States ; T32 MH020068/MH/NIMH NIH HHS/United States ; },
abstract = {Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) overlap considerably in genetic origin and pathology. Multiple C. elegans models of ALS/FTD have been developed, but the integrity of glutamatergic neurons in these models has not been thoroughly evaluated. Here, we report degeneration of glutamatergic phasmid neurons in animals expressing either wild-type or disease variant V337M human tau, and mild degeneration in animals expressing disease variant M337V human TDP-43. Defects caused by ectopic expression of tau were suppressed by loss of the known modifier, spop-1 , suggesting that SPOP-1-dependent pathways are also involved in glutamatergic neuron degeneration.},
}

@article {pmid42688563,
year = {2026},
author = {Gao, X and Wang, T and Chen, S and Ma, Y and Wei, Q and Li, C and Shang, H and Chen, X},
title = {Amyotrophic lateral sclerosis -plus patient with an intermediate-length CACNA1A allele: a Case Report.},
journal = {Frontiers in genetics},
volume = {17},
number = {},
pages = {1860828},
pmid = {42688563},
issn = {1664-8021},
abstract = {Amyotrophic lateral sclerosis (ALS), the most common type of motor neuron disease, primarily manifests as progressive weakness, atrophy, fasciculations, bulbar palsy, and pyramidal tract symptoms. Accumulating evidence indicates that the pathological spectrum of ALS extends beyond the pyramidal and neuromuscular motor systems, involving additional brain regions, manifesting as ALS-plus syndrome. We present a case of an elderly woman with bulbar-onset ALS accompanied by cerebellar manifestations and an intermediate-length CACNA1A allele. Based on the Gold Coast criteria, ALS diagnosis was made. Notably, the patient exhibited cognitive impairment and a positive Romberg sign, suggesting a broader phenotypic spectrum. Genetic analysis showed a CAG repeat genotype of 10/20 in the CACNA1A gene. The patient's son carried a 14/20 genotype and displayed isolated cerebellar ataxia without motor neuron features. We reviewed the literature on spinocerebellar ataxia (SCA) co-occurring with motor neuron disease and discussed the uncertain significance of the intermediate-length CACNA1A allele in this context, weighing coincidental co-occurrence against a potential causal link. To our knowledge, this case is the first reported instance of an intermediate-length CACNA1A allele co-occurring with ALS in Chinese population, although the association between the allele and ALS remains unclear.},
}

@article {pmid42689185,
year = {2026},
author = {Sun, L and Yu, X and Yin, H and Bi, J and Lou, H and Pei, H},
title = {A recent review on ginseng's effects on neurodegenerative diseases: active ingredients, mechanisms of action, applications, and delivery strategies.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1912520},
pmid = {42689185},
issn = {2296-861X},
abstract = {BACKGROUND: Neurodegenerative diseases (NDDs) pose a major health challenge due to their high prevalence and the lack of effective treatments; ginseng, as medicine and food homology, has potential neuroprotective effects.

METHODS: This article provides a systematic review of research conducted over the past five years on the use of ginseng to treat NDDs, summarizing and analyzing the findings in four key areas: active components, mechanisms of action, clinical applications, and novel delivery strategies.

RESULTS: Ginsenosides are the core active ingredients in ginseng, while polysaccharides, essential oils, and peptides also exert synergistic effects through various pathways; their mechanisms of action include regulating Aβ/tau protein aggregation, inhibiting microglial activation, reducing glutamate excitotoxicity, and restoring mitochondrial function and antioxidant balance. In models of AD, PD, HD, and ALS, ginseng's active components have been shown to improve both behavioral and pathological indicators, while novel delivery strategies (nanoparticles, exosomes, and engineered cellular carriers) can significantly enhance blood-brain barrier permeability and brain-targeting efficiency.

CONCLUSION: Ginseng exhibits protective effects against NDDs through multiple mechanisms of action. However, current evidence is largely limited to preclinical studies, and future efforts should focus on advancing the clinical translation of safe and effective brain-targeted delivery systems.},
}

@article {pmid42690718,
year = {2026},
author = {Nam, MK and Oh, Y and Choi, Y and Lee, J and Jeong, GH and Park, S and Yoo, SA and Kim, M and Kang, S and Rhim, H},
title = {Mechanistic Characterization of NABi as a Selective Inhibitor of SOD1G93A Aggregation: Structural Basis and Therapeutic Implications for ALS.},
journal = {ACS chemical neuroscience},
volume = {17},
number = {17},
pages = {3156-3168},
doi = {10.1021/acschemneuro.5c00977},
pmid = {42690718},
issn = {1948-7193},
support = {RS-2022-NR070495//National Research Foundation of Korea/ ; RS-2026-25504267//National Research Foundation of Korea/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/genetics ; *Superoxide Dismutase-1/metabolism/genetics ; Humans ; Animals ; Mutation ; *Superoxide Dismutase/metabolism/genetics ; Protein Aggregates/drug effects ; *Protein Aggregation, Pathological/drug therapy/metabolism ; Amyloid beta-Peptides/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons, with familial ALS (fALS) frequently caused by mutations in Cu/Zn superoxide dismutase (SOD1). The G93A mutation, one of the most aggressive forms, promotes the formation of cytotoxic protein aggregates through cross-β-sheet structures, leading to neuronal dysfunction and death. In this study, we investigated the therapeutic potential of NABi (natural Aβ binder and Aβ-aggregation inhibitor), a stable small engineered protein composed of the N-terminal 90 amino acids of SOD1, originally developed to target amyloid-β aggregation in Alzheimer's disease. Given the shared β-sheet-rich aggregation mechanisms between amyloid-β and mutant SOD1 proteins, we hypothesized that NABi could serve as a dual-action therapeutic for both diseases. Through an integrated approach involving structural, biochemical, and cellular analyses, we demonstrate that NABi exhibits a 4-fold greater binding affinity for SOD1G93A compared to SOD1WT, selectively targeting the mutant protein via specific hydrophobic interactions. Structural modeling using AlphaFold2 reveals that the G93A mutation exposes hydrophobic residues that create an optimal binding interface for NABi. Functionally, NABi effectively inhibits SOD1G93A aggregation, as demonstrated by filter trap assays and immunofluorescence microscopy, while maintaining the protein in a soluble, nontoxic state. Importantly, coexpression of NABi reduces SOD1G93A-induced cytotoxicity by approximately 4-fold, significantly enhancing neuronal survival. These findings establish NABi as a promising therapeutic candidate for SOD1G93A-associated familial ALS, demonstrating its capacity to selectively target pathological protein conformations while preserving normal cellular function. Our results support the development of NABi as an innovative pan-therapeutic approach targeting shared aggregation pathways across multiple neurodegenerative diseases.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/genetics
*Superoxide Dismutase-1/metabolism/genetics
Humans
Animals
Mutation
*Superoxide Dismutase/metabolism/genetics
Protein Aggregates/drug effects
*Protein Aggregation, Pathological/drug therapy/metabolism
Amyloid beta-Peptides/metabolism

@article {pmid42681595,
year = {2026},
author = {Lehrer, S and Rheinstein, PH},
title = {Proteomic and Functional Signatures of Phenoconversion in Presymptomatic Amyotrophic Lateral Sclerosis.},
journal = {Journal of clinical neuromuscular disease},
volume = {28},
number = {1},
pages = {33-46},
doi = {10.1097/CND.0000000000000567},
pmid = {42681595},
issn = {1537-1611},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood/genetics/diagnosis ; Female ; Proteomics ; Male ; Middle Aged ; Biomarkers/blood ; C9orf72 Protein/genetics ; Aged ; Neurofilament Proteins/blood ; *Prodromal Symptoms ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) likely has a prolonged presymptomatic phase. Identifying blood biomarkers that predict phenoconversion is critical for early intervention.

METHODS: We analyzed baseline serum proteomics in 270 UK Biobank participants who later developed ALS. A prespecified 19-protein panel was evaluated in relation to time-to-diagnosis. C9orf72 risk was proxied using rs10757668 genotype.

RESULTS: Neurofilament light rose sharply in the 2-3 years preceding diagnosis (r = -0.37, P < 0.001). Muscle-stress markers, including EDA2R and MYL3, increased earlier, up to 4-6 years before onset. Higher EDA2R levels were associated with reduced grip strength at baseline. A combined 19-protein panel plus genotype predicted phenoconversion within 3 years with an area under the receiver operating characteristic curve of 0.77, outperforming neurofilament light alone.

CONCLUSIONS: ALS exhibits a measurable molecular prodrome detectable in blood years before diagnosis. Integrated proteomic and genetic profiling may support early identification and trial enrichment strategies.},
}

Humans
*Amyotrophic Lateral Sclerosis/blood/genetics/diagnosis
Female
Proteomics
Male
Middle Aged
Biomarkers/blood
C9orf72 Protein/genetics
Aged
Neurofilament Proteins/blood
*Prodromal Symptoms

@article {pmid42681642,
year = {2026},
author = {German, A and Grotemeyer, A and Koller, K and Eckstein, M and Wolff, H and Rampp, S and Süß, P and Müller, VC and Birnbacher, D and Winkler, J and Regensburger, M},
title = {Organ donation and brain preservation after assisted dying: case report and considerations for a potential pathway.},
journal = {BMC medical ethics},
volume = {27},
number = {1},
pages = {},
pmid = {42681642},
issn = {1472-6939},
mesh = {Humans ; *Tissue and Organ Procurement/ethics ; Germany ; *Suicide, Assisted/ethics ; *Organ Preservation/ethics ; *Brain ; Brain Death ; Cryopreservation ; },
abstract = {Protecting life and restoring health have been at the core of the conception of medical care since antiquity, for health professionals and the public alike. Assisted dying represents a practice that appears to challenge this traditional conception. In jurisdictions where assisted dying is condoned, the question remains as to whether the practice should be medicalized or deferred to non-medical actors. Irrespective of the divisive controversy surrounding assisted dying and its medicalization per se, the practice gives rise to high-stakes ethical, legal and organizational challenges when intersecting with organ transplantation, tissue banking, and Structural Brain Preservation or cryonics. In this narrative account, we describe the contextual framework and outline our experience and operational scope for addressing them at a university hospital in Germany. Based on this description we propose a structured pathway for increasing donation and preservation options for terminal patients while retaining ethical integrity and professional accountability.},
}

Humans
*Tissue and Organ Procurement/ethics
Germany
*Suicide, Assisted/ethics
*Organ Preservation/ethics
*Brain
Brain Death
Cryopreservation

@article {pmid42681667,
year = {2026},
author = {Sowoidnich, L and Norman, AL and Gerstner, F and Siemund, JK and Buettner, JM and Pagiazitis, JG and Dreilich, V and Pilz, K and Tian, D and Sumner, CJ and Paradis, A and Mentis, GZ and Simon, CM},
title = {A standardized framework resolves ambiguity in motor neuron loss across neurodegenerative diseases.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {},
pmid = {42681667},
issn = {2051-5960},
mesh = {Animals ; Humans ; *Motor Neurons/pathology ; *Neurodegenerative Diseases/pathology ; *Spinal Cord/pathology ; Muscular Atrophy, Spinal/pathology ; Mice ; Disease Models, Animal ; },
abstract = {Motor neuron (MN) loss is a hallmark of neurodegenerative disorders, yet its assessment remains variable, confounding mechanistic and therapeutic interpretation. To address this, we conducted a systematic review and meta-analysis of spinal muscular atrophy (SMA) mouse studies, revealing 60% variability in reported MN loss, for which spinal cord sampling emerged as a major contributor. Using a whole-segment approach with tissue clearing, MN tracing, and multimodal imaging, we confirmed segment-dependent differences in MN counts. Common MN markers (SMI-32, Nissl) lacked specificity, whereas choline acetyltransferase (ChAT) provided robust labeling in murine and human spinal cords. Deep learning-based whole-mount segmentation enabled unbiased MN quantification and validated manual counts. Integrating analysis with computational modeling established segment sampling as a key driver of variability and revealed degeneration patterns: widespread MN loss in amyotrophic lateral sclerosis (ALS), selective MN loss in severe SMA, and preservation in mild SMA models. These findings establish a framework for reproducible MN quantification.},
}

Animals
Humans
*Motor Neurons/pathology
*Neurodegenerative Diseases/pathology
*Spinal Cord/pathology
Muscular Atrophy, Spinal/pathology
Mice
Disease Models, Animal

@article {pmid42682425,
year = {2026},
author = {Niu, X and Zhang, M and Huang, H and Shao, B and Wang, X and Cai, Z},
title = {Increased serum fibroblast growth factor 2 levels, altered peripheral blood inflammatory indicators and their ratios in amyotrophic lateral sclerosis: a clinical exploratory study.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1859903},
pmid = {42682425},
issn = {1664-2295},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/blood ; Female ; *Fibroblast Growth Factor 2/blood ; Male ; Case-Control Studies ; Middle Aged ; Biomarkers/blood ; Prospective Studies ; Aged ; *Inflammation/blood ; Adult ; Disease Progression ; Neutrophils ; },
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration, leading to muscle weakness, atrophy, and ultimately respiratory failure. Previous research has highlighted the roles of neurotrophic factors and inflammatory responses in ALS pathogenesis; however, their interplay remains poorly understood. This exploratory study aims to elucidate the expression characteristics and correlations of fibroblast growth factor 2 (FGF2) and peripheral blood inflammatory indicators (PBIIs) such as derived neutrophil-to-lymphocyte ratio (dNLR) and systemic inflammatory response index (SIRI) in ALS patients.

METHODS: This was a prospective case-control study, involving ALS patients meeting Gold Coast diagnostic criteria and age- and sex-matched healthy controls (HCs). Serum FGF2 levels were measured using enzyme-linked immunosorbent assay (ELISA), and PBIIs were assessed through routine blood analysis. Statistical analysis was conducted mainly using intergroup comparison, correlation analysis, and multivariate linear regression.

RESULTS: The results showed significantly elevated levels of FGF2 and PBIIs in ALS patients compared to HCs, with strong correlations between FGF2, PBIIs, clinical staging, and disease progression rates. In multivariate linear regression analysis, PBIIs, especially SIRI, were significantly associated with disease severity and early disease progression. While serum FGF2 and FGF2 to dNLR ratio demonstrated potential as an auxiliary biomarker for later-stage disease.

DISCUSSION: These findings provide new insights into the molecular mechanisms underlying ALS and suggest practical diagnostic and prognostic tools, reinforcing the importance of targeting neurotrophic and inflammatory pathways in ALS management. This study holds significant promise for advancing both clinical practice and future research endeavors in the field.},
}

Humans
*Amyotrophic Lateral Sclerosis/blood
Female
*Fibroblast Growth Factor 2/blood
Male
Case-Control Studies
Middle Aged
Biomarkers/blood
Prospective Studies
Aged
*Inflammation/blood
Adult
Disease Progression
Neutrophils

@article {pmid42682698,
year = {2026},
author = {AlNujaidi, HY and Al-Rayes, SA and Alumran, A and Almukhadhib, OY and AlNujaidi, DY and Alhafid, IA and Alyousif, GF},
title = {Construct validation of HER-WELL: a bifactor exploratory structural equation modeling evaluation of an eight-domain wellness scale for women.},
journal = {Frontiers in global women's health},
volume = {7},
number = {},
pages = {1903478},
pmid = {42682698},
issn = {2673-5059},
abstract = {BACKGROUND: Wellness is a multidimensional latent construct whose valid assessment requires psychometrically robust, culturally adapted instruments; however, existing scales have been predominantly developed in Western contexts and remain inadequate for capturing the gendered and sociocultural dimensions of women's wellness in non-Western settings. This study aimed to develop and psychometrically validate the HER-WELL scale, a culturally adapted multidimensional measure of holistic wellness for Saudi women.

METHODS: Scale development followed Boateng et al.'s (2018) framework, and construct validity was tested in RStudio and Mplus by comparing six measurement models (final CFA, ESEM, second-order CFA, bifactor CFA, second-order ESEM, bifactor ESEM) estimated with robust WLSMV and TARGET rotation in a stratified community sample of Saudi women (N = 1,068; 531 employed, 537 non-employed), with model fit (CFI, TLI, RMSEA, SRMR) evaluated against conventional and Dynamic Fit Index cutoffs.

RESULTS: HER-WELL items showed adequate variability, with the highest endorsement for Home Environment, social, and spiritual wellness and the lowest for physical wellness. Across employed, non-employed, and full samples, bifactor ESEM consistently provided the best representation of the data, with excellent fit (CFI ≈.99, TLI ≈.98, RMSEA ≈.03, SRMR ≈.02) that exceeded both conventional and DFI-tailored cutoffs. This structure supported a strong general women's wellness factor, with Physical, Financial, Mental, and Occupational wellness retaining sufficient domain-specific variance, while Emotional, Social, Spiritual, and Home Environmental wellness were more strongly saturated by the general factor and are best interpreted as expressions of overall wellness. Internal consistency was acceptable for most domains (ω and α typically ≥.80), with Home Environmental wellness showing the weakest reliability and specific-factor indices of any domain (ω ≈.77; AVE =.070-.122), and should be interpreted only via the total score.

CONCLUSION: ER-WELL demonstrates strong psychometric properties as a culturally validated measure of holistic wellness for Saudi women. The bifactor ESEM solution supports the simultaneous use of overall wellness scores alongside domain-specific profiles for Physical, Financial, Mental, and Occupational wellness for research, surveillance, and intervention evaluation in Saudi Arabia and similar Arab and Muslim-majority contexts.},
}

@article {pmid42682963,
year = {2026},
author = {Albaji, M and Ashkboos, K and Bagherzadeh, K},
title = {Possible Paraneoplastic Amyotrophic Lateral Sclerosis Presenting as Respiratory Failure in a Breast Cancer Patient: A Case Report.},
journal = {Clinical case reports},
volume = {14},
number = {9},
pages = {e73447},
pmid = {42682963},
issn = {2050-0904},
abstract = {A 63-year-old female with metastatic breast cancer presented with acute hypercapnic respiratory failure secondary to severe diaphragmatic dysfunction and mixed upper and lower motor neuron signs. Serum onconeural and neural surface antibody panels were negative, and initial cerebrospinal fluid analysis revealed albuminocytologic dissociation. Immunotherapy with intravenous immunoglobulin (IVIG) produced no clinical improvement, necessitating invasive mechanical ventilation and gastrostomy. Applying the 2021 PNS-Care consensus criteria, the case fulfills criteria for possible paraneoplastic amyotrophic lateral sclerosis (ALS), although coincidental sporadic disease cannot be excluded. A markedly elevated erythrocyte sedimentation rate (ESR) was observed, largely attributable to skeletal metastases and localized pulmonary collapse. Clinicians must maintain a high index of suspicion for motor neuron disease in cancer patients with unexplained hypoventilation.},
}

@article {pmid42684486,
year = {2026},
author = {Bencs, V and Hortobágyi, T and Nagy, AC and Kozák, M and Méhes, G and Oláh, L and Csiba, L},
title = {Establishment of a novel human nervous system tissue bank: University of Debrecen tissue bank-introduction and retrospective data analysis.},
journal = {Cell and tissue banking},
volume = {27},
number = {4},
pages = {},
pmid = {42684486},
issn = {1573-6814},
mesh = {Humans ; Female ; *Tissue Banks ; Male ; Retrospective Studies ; Middle Aged ; Aged ; *Brain/pathology ; Adult ; Aged, 80 and over ; Autopsy ; Adolescent ; Young Adult ; Paraffin Embedding ; Child ; },
abstract = {Human brain tissues obtained from autopsies, as well as muscle and nerve samples derived from biopsies, constitute indispensable resources for translational research investigating the pathomechanisms of neuropsychiatric disorders. In this study, we introduce the Nervous System Tissue Bank of University of Debrecen, which contains formalin-preserved and formalin-fixed paraffin-embedded (FFPE) brain samples, as well as frozen nerve and muscle biopsy specimens. Database was established containing clinical and pathological parameters. For autopsy cases, the following variables were recorded: sex, age, number of hospitalization days, admission diagnosis, comorbidities, cause of death, post-mortem interval, general autopsy findings, and macro- and microscopic brain pathology diagnoses. For biopsy samples, we recorded: sex, age, biopsy site, and microscopic and molecular genetic diagnoses. Based on the recorded parameters and their temporal changes, retrospective statistical analyses were performed. Formalin-fixed brain samples and FFPE blocks were available from 2425 deceased individuals, and nerve/muscle samples from 257 patients. The brain samples originate from the period between 1990 and 2012. The most frequent admission diagnoses included ischemic stroke (n = 1070), hemorrhagic stroke (n = 462), subarachnoid hemorrhage (n = 102), epilepsy (n = 103), brain metastasis (n = 70), primary brain tumor (n = 60), parkinsonism (n = 28), dementia (n = 21), and amyotrophic lateral sclerosis (n = 21). Prevalence of hypertension (67.6%) and diabetes mellitus (20.1%) showed a significant increase over time (p < 0.001), whereas the prevalence of malignancies, dementia, parkinsonism, and psychiatric disorders remained stable. Our tissue bank represents the largest nervous system collection in Hungary, providing well-characterized brain, muscle, and nerve samples linked to nearly three decades of clinical data. Samples are made available to researchers.},
}

Humans
Female
*Tissue Banks
Male
Retrospective Studies
Middle Aged
Aged
*Brain/pathology
Adult
Aged, 80 and over
Autopsy
Adolescent
Young Adult
Paraffin Embedding
Child

@article {pmid42684942,
year = {2026},
author = {Huang, D and Zhang, Z and Gong, X},
title = {Context-dependent roles of osteopontin in aging-related neurological disorders.},
journal = {The Journal of international medical research},
volume = {54},
number = {9},
pages = {3000605261476190},
pmid = {42684942},
issn = {1473-2300},
mesh = {Humans ; *Osteopontin/metabolism ; *Aging/pathology/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Brain/pathology/metabolism ; Alzheimer Disease ; Microglia/metabolism ; },
abstract = {Osteopontin (encoded by secreted phosphoprotein 1) is a multifunctional matricellular phosphoglycoprotein that has emerged as an important mediator in the aging nervous system. During aging, osteopontin interacts with microglial priming, vascular remodeling, myelin repair, and innate immune responses and is consistently implicated in major late-life neurological disorders. However, its biological effects are highly context dependent. Depending on its cellular source, proteolytic processing, receptor interactions, anatomical distribution, and disease stage, osteopontin may either exacerbate chronic neuroinflammation and tissue injury or promote phagocytic clearance, neuronal survival, remyelination, neuroplasticity, and tissue repair. This review critically synthesizes studies indexed in PubMed and Google Scholar through 3 April 2026 on the role of osteopontin in brain aging, Alzheimer's disease and related dementias, Parkinson's disease and Lewy body disorders, cerebrovascular disease, vascular cognitive impairment, cerebral small vessel disease, and amyotrophic lateral sclerosis. In Alzheimer's disease, cerebrospinal fluid and plasma osteopontin concentrations increase from the prodromal to symptomatic stages, whereas microglial or perivascular secreted phosphoprotein 1 expression correlates with amyloid pathology, synaptic remodeling, and cognitive decline. However, under specific conditions, osteopontin also enhances macrophage-mediated amyloid-beta clearance. In stroke, elevated circulating osteopontin predicts poor clinical outcomes, whereas experimental studies demonstrate that appropriately timed exogenous osteopontin, regulatory T cell-derived osteopontin, and osteopontin-mediated autophagic and reparative pathways promote white-matter repair, peri-infarct plasticity, and blood-brain barrier integrity. Evidence from Parkinson's disease, Lewy body disease, frontotemporal dementia, and amyotrophic lateral sclerosis further supports the role of osteopontin as both a candidate biomarker and a regulator of selective neuronal vulnerability. Rather than being uniformly detrimental or protective, osteopontin should be regarded as a context-dependent regulator of age-related neuroimmune remodeling. This perspective reconciles seemingly conflicting findings and supports the development of therapeutic strategies that are tailored to disease stage, protein fragment, and cell type rather than broadly targeting osteopontin.},
}

Humans
*Osteopontin/metabolism
*Aging/pathology/metabolism
Animals
*Nervous System Diseases/metabolism/pathology
Brain/pathology/metabolism
Alzheimer Disease
Microglia/metabolism

@article {pmid42685299,
year = {2026},
author = {Benatar, M and Rothstein, JD and Snow, K and Sethi, N and Taylor, DM and Dave, KD and McDermott, CJ and Cochrane, TI},
title = {Repairing the Amyotrophic Lateral Sclerosis Trial Credibility Gap.},
journal = {Neurology},
volume = {107},
number = {7},
pages = {e218471},
doi = {10.1212/WNL.0000000000218471},
pmid = {42685299},
issn = {1526-632X},
mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Clinical Trials as Topic/standards ; *Research Design/standards ; },
abstract = {There is a long history of early- and mid-phase amyotrophic lateral sclerosis (ALS) clinical trial data being used to make claims of clinical benefit that fail to translate into successful phase 3 outcomes. It is suggested that fallacious scientific reasoning is being encouraged by perverse incentives arising from a "clinical trial industrial complex" that greatly influences trial design, data interpretation, and results communication. Recurring fallacies include false premises underlying outcome comparisons, misuse and incorrect interpretation of biomarkers, mismatches between study design and stated objectives, selective reporting of outcomes, over-reliance on post hoc analyses and open-label extension data, and overly optimistic framing of inconclusive data. We argue that these practices, reinforced by misaligned incentives across industry and academia, lead to premature claims of therapeutic promise and tangible harm to patients. To address the resulting ALS clinical trial credibility gap, we call for rigorous adherence to established standards for reporting clinical trial results, clearer distinction between hypothesis generation and hypothesis testing, more measured description of trial results, and more disciplined triage of phase 2 programs. A cultural shift toward scientific skepticism and methodological rigor is essential to accelerate the development of genuinely effective ALS therapies.},
}

*Amyotrophic Lateral Sclerosis/therapy
Humans
*Clinical Trials as Topic/standards
*Research Design/standards

@article {pmid42685382,
year = {2026},
author = {Ni, CC and Yu, CS and Wei, SY and Dai, JZ and Chang, CL and Ting, HC and Chang, CY and Chen, YC},
title = {UV-programmed gelatin methacryloyl hydrogel microenvironments reveal a bell-shaped vascularization window and enable compartmentalized neuromuscular disease modeling.},
journal = {Biomaterials},
volume = {338},
number = {Pt A},
pages = {124588},
doi = {10.1016/j.biomaterials.2026.124588},
pmid = {42685382},
issn = {1878-5905},
abstract = {Matrix mechanics and microarchitecture jointly regulate tissue morphogenesis and functional maturation; however, defining their combined effects remains challenging when microenvironmental tuning requires changes in material composition. Here, we establish a UV-programmable gelatin methacryloyl (GelMA) hydrogel system in which ultraviolet exposure coordinates changes in construct architecture, pore morphology, and apparent mechanical properties within a constant material formulation. This framework enables systematic mapping of biological responses to UV-programmed architectural-mechanical microenvironments without compositional confounders. In vivo subcutaneous implantation reveals a nonlinear, bell-shaped vascularization response to UV-programmed GelMA hydrogel properties, identifying a narrow microenvironmental window that supports blood-containing vessel formation, human-derived vascular structures, and host-perfused vascular integration. For neuromuscular modeling, a structurally stable UV-defined regime was selected to support long-term compartmentalized co-culture of human induced pluripotent stem cell-derived myoblasts and motor neuron spheroids. Within this same UV-defined compartmentalized neuromuscular microenvironment, amyotrophic lateral sclerosis (ALS)-derived constructs exhibit impaired myogenic maturation, reduced neuromuscular junction (NMJ)-like structural organization, and altered contractile responsiveness compared with gene-corrected Healthy controls. Pharmacological treatment with the FDA-approved drug Riluzole partially restores these disease-associated phenotypes. Together, these findings establish UV-programmed GelMA hydrogels as an adaptable architectural-mechanical platform for identifying vascularization-permissive microenvironments and supporting compartmentalized neuromuscular disease modeling.},
}

@article {pmid42685551,
year = {2026},
author = {Kashif, M and Keating, ME and Byrne, HJ},
title = {Approaches to data mining reaction kinetics using Raman spectroscopic analysis of Claisen-Schmidt condensation as a model.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {365},
number = {},
pages = {128685},
doi = {10.1016/j.saa.2026.128685},
pmid = {42685551},
issn = {1873-3557},
abstract = {Raman spectroscopy provides a powerful, non-destructive tool for real-time monitoring of multicomponent kinetics. However, extraction of reliable kinetic information from kinetically evolving Raman data can be challenging, due to the degree of spectral overlap of constituent signatures, rank deficiency, and rotational ambiguity. In this work, as a model reaction, solvent-free, base-catalysed Claisen-Schmidt condensation between benzaldehyde and acetone at room temperature was monitored using Raman microspectroscopy, in-situ, over a timescale of 1000 min. The resulting multicomponent dataset was analysed using problem-based nonlinear least squares (NLS) fitting of the weighted sums of the spectra of the reaction components, and multivariate curve resolution-alternating least squares (MCR-ALS) analysis. Three and four-components models were explored within the NLS framework, while a mechanistically constrained model (A + B → C, C + A → D) was implemented for MCR-ALS hard modelling. Conventional soft and hard MCR-ALS approaches failed to identify the correct reaction components and resolve chemically meaningful profiles, whereas seeded MCR-ALS, with 10,000× optimized seed weightings, successfully overcame these failings and yielded physically consistent spectra and concentration profiles. Reaction kinetics were evaluated by fitting the resolved concentration profiles to a kinetic model (A → C → D). The seeded MCR-ALS approach provided the most reliable kinetic description, while, in comparison, NLS based approaches using resolved and pure components spectra exhibited lower fitting accuracy. Quantitatively, the seeded MCR-ALS model showed superior performance, co-efficient of determination (R[2]) = 0.935, residual sum of squares (RSS) = 0.156, relative residual error (RRE) = 0.70% relative to NLS using resolved spectra (R[2] = 0.782, RSS = 0.524, RRE = 2.34%) and NLS using pure spectra (R[2] = 0.783, RSS = 0.408, RRE = 2.33%). These results demonstrate that seeded MCR-ALS, combined with constrained exponential kinetic modelling provides a robust and physically consistent framework for resolving spectroscopic data and extracting reliable mechanistic and kinetic insights. The proposed methodology is broadly applicable to complex multicomponent systems, including metabolomics, process analytics, and pharma kinetics, in which severe spectral overlap and rank deficiency limit conventional analytical approaches.},
}

@article {pmid42685707,
year = {2026},
author = {Metelmann, C and Gräsner, JT and Jacobsen, N and Neuenfeldt, FJ},
title = {[European Resuscitation Council Guidelines 2025: Basic and Advanced Life Support].},
journal = {Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS},
volume = {61},
number = {9},
pages = {531-547},
doi = {10.1055/a-2931-2870},
pmid = {42685707},
issn = {1439-1074},
mesh = {Humans ; *Cardiopulmonary Resuscitation/standards/methods ; Europe ; *Advanced Cardiac Life Support/standards ; Heart Arrest/therapy ; *Practice Guidelines as Topic ; Emergency Medical Services/standards ; },
abstract = {The 2025 European Resuscitation Council (ERC) guidelines introduce updated recommendations for adult Basic Life Support (BLS) and Advanced Life Support (ALS), with a strong focus on early recognition, high-quality cardiopulmonary resuscitation (CPR), timely defibrillation, and physiologically guided resuscitation. This article summarizes the most relevant changes and practical implications for healthcare professionals and bystander.},
}

Humans
*Cardiopulmonary Resuscitation/standards/methods
Europe
*Advanced Cardiac Life Support/standards
Heart Arrest/therapy
*Practice Guidelines as Topic
Emergency Medical Services/standards

@article {pmid42686219,
year = {2026},
author = {Liu, J and Lin, J and Liu, H and Soh, K and Ju, Q and Soh, K and Dong, X},
title = {Efficacy of Antimicrobial Lock Solutions on Central Line-Associated Bloodstream Infection and Catheter Survival in Hemodialysis Patients: A Systematic Review and Meta-Analysis.},
journal = {Seminars in dialysis},
volume = {},
number = {},
pages = {},
doi = {10.1111/sdi.70046},
pmid = {42686219},
issn = {1525-139X},
support = {202301A014//Chengde Science and Technology Program/ ; GJXH2021-126//Hebei Higher Education Association "14th Five-Year Plan" Research Project/ ; H2026406068//Hebei Natural Science Foundation/ ; 202307//Chengde Medical university Project/ ; 202404//Chengde Medical university Project/ ; },
abstract = {Hemodialysis (HD) catheters carry a high risk of life-threatening bloodstream infections and failure. Antimicrobial lock solutions (ALS) are used to reduce this risk, but their overall efficacy on key outcomes like infection rates and catheter survival requires comprehensive evaluation. This systematic review and meta-analysis assess the impact of ALS on preventing catheter-related bloodstream infections (including incidence and density) and on improving catheter survival. A systematic search was conducted across the databases of PubMed, Embase, Scopus, Cochrane Library, and Google Scholar. A meta-analysis was conducted using STATA software. A total of 1183 studies were screened based on title and abstract, and further 282 studies were evaluated in full text. Eventually, 14 studies with 15 treatment arms were included. Key outcomes including central line-associated bloodstream infection (CLABSI), exit infection, and catheter-free survival were conducted separately. ALS demonstrated statistically significant benefits on CLABSI infection and catheter-free survival compared to nonantimicrobial solutions, showing a reduction in CLABSI density with a pooled log odd ratio (logOR) of -1.29 (95% CI: -1.59 to -0.99), lower CLABSI rates (pooled logOR = -1.50, 95% CI: -1.85 to -1.15), and improved catheter-free survival with log hazard ratio (logHR) of -1.11 (95% CI: -1.41 to -0.8). Consistent treatment effects were observed across all lock types with no significant heterogeneity detected. ALS demonstrate statistically significant and clinically important efficacy in reducing CLABSI incidence and density while improving catheter survival in HD patients, establishing them as an essential preventive strategy in clinical practice.},
}

@article {pmid42678590,
year = {2026},
author = {Ahmad, R and Naeem, M and Houlden, H},
title = {Whole-exome sequencing reveals a novel frameshift and a recurrent nonsense SPG11 variant causing rare familial amyotrophic lateral sclerosis type 5 in two consanguineous Pakistani families.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42678590},
issn = {1573-4978},
mesh = {Humans ; Pakistan ; Female ; Male ; Exome Sequencing/methods ; Pedigree ; *Amyotrophic Lateral Sclerosis/genetics ; Consanguinity ; Adult ; Frameshift Mutation/genetics ; Codon, Nonsense/genetics ; *Proteins/genetics ; Homozygote ; Phenotype ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both upper and lower motor neurons, disturbing communication between the brain and muscles. So far, few reports have been published for the SPG11-associated ALS, and this is the first documented case from Pakistan. METHODS: We report a rare subtype of ALS with an autosomal recessive mode of inheritance with juvenile onset before 25 years of age in the five affected individuals from two unrelated families. Whole-exome sequencing was performed to identify disease-causing variants, and selected variants were further prioritized based on predicted pathogenicity and similarity to clinical phenotypes.

RESULTS: Two homozygous variants within the SPG11 gene were identified as pathogenic according to the ACMG and ClinGen Sequence Variant Interpretation (SVI) Working Group recommendations: a novel truncation (NM_025137.4:c.6738dup, p.Glu2247Ter) variant as validated by Sanger sequencing and a recurrent nonsense (NM_025137.4: c.782C>A, p.Ser261Ter) variant (rs765477482) previously reported in a family affected with autosomal recessive hereditary spastic paraplegia (ARHSP). In silico prediction tools further confirmed their pathogenicity.

CONCLUSION: Five patients with juvenile-onset ALS born to consanguineous parents were found to have homozygous SPG11 gene variants. Our findings describe the overlapping phenotypes ofSPG11-related autosomal recessive juvenile ALS and ARHSP, suggesting that these disorders show a clear overlapping phenotype with common genetic defects. In clinical practice, it is challenging to distinguish between these two disorders. Additional Mendelian cases should be included to clarify further and investigate whether these represent two diverse diseases caused by variants in a single gene.},
}

Humans
Pakistan
Female
Male
Exome Sequencing/methods
Pedigree
*Amyotrophic Lateral Sclerosis/genetics
Consanguinity
Adult
Frameshift Mutation/genetics
Codon, Nonsense/genetics
*Proteins/genetics
Homozygote
Phenotype

@article {pmid42679713,
year = {2026},
author = {Özbey, H and Beşiktaş, S and Bayat, M},
title = {Validation of the Turkish caring professional scale among mothers of hospitalized neonates: A psychometric study based on Swanson's theory of caring.},
journal = {Journal of pediatric nursing},
volume = {91},
number = {},
pages = {546-553},
doi = {10.1016/j.pedn.2026.08.055},
pmid = {42679713},
issn = {1532-8449},
abstract = {INTRODUCTION: The aim is to adapt the CPS into Turkish and evaluate its psychometric properties specifically among mothers of hospitalized neonates.

METHODS: This cross-sectional study included 149 mothers at a university hospital NICU. Cross-cultural adaptation followed Beaton et al.'s five-stage framework. Psychometric evaluation included internal consistency (Cronbach's α and McDonald's ω), confirmatory factor analysis (CFA) using both maximum likelihood on Pearson correlations and unweighted least squares on polychoric correlations, convergent and discriminant validity, and criterion-related validity with the Barrett-Lennard Relationship Inventory empathy subscale.

RESULTS: The Turkish CPS demonstrated excellent internal consistency (α = 0.961, ω = 0.911). The two-factor model showed excellent fit under polychoric-ULS estimation (CFI = 0.99, RMSEA = 0.001, SRMR = 0.046), and all standardized factor loadings exceeded 0.75. However, the one-factor and two-factor models showed almost identical fit, and the two subscales were highly overlapping, indicating that discriminant validity between them was not established. Significant positive correlations with empathy scores provided support for criterion validity.

CONCLUSION: The Turkish CPS demonstrates strong internal consistency and provides initial evidence for model fit in the NICU; however, discriminant validity between the two subscales was not supported, and the total score may be more appropriate than subscale-level interpretation. The findings support the cross-cultural applicability of Swanson's Theory of Caring and emphasize the necessity of using polychoric-based CFA methods for ordinal nursing data.

IMPLICATIONS TO PRACTICE: The Turkish CPS provides pediatric nurses and researchers with a brief, theory-based tool to assess maternal perceptions of professional caring in the NICU.},
}

@article {pmid42680205,
year = {2026},
author = {Hines, TJ and Funke, JR and Pratt, SL and Rice, AD and Twiss, JL and Burgess, RW},
title = {A mouse model of autosomal dominant spastic ataxia and myopathy caused by a mutation in Tuba4a.},
journal = {Human molecular genetics},
volume = {35},
number = {18},
pages = {},
doi = {10.1093/hmg/ddag084},
pmid = {42680205},
issn = {1460-2083},
support = {R01 NS068933//National Institute of Neurological Diseases and Stroke/ ; R37 NS054154//National Institute of Neurological Diseases and Stroke/ ; K99 NS130151//National Institute of Neurological Diseases and Stroke/ ; },
mesh = {Animals ; Disease Models, Animal ; Mice ; Male ; *Spinocerebellar Ataxias/genetics/pathology ; *Muscle Spasticity/genetics/pathology ; *Muscular Diseases/genetics/pathology ; *Tubulin/genetics ; Humans ; *Intellectual Disability/genetics/pathology ; *Optic Atrophy/genetics/pathology ; Mice, Inbred C57BL ; Mutation, Missense ; Polymorphism, Single Nucleotide ; Mutation ; Genes, Dominant ; Female ; Protein Serine-Threonine Kinases/genetics ; Muscle, Skeletal/pathology ; },
abstract = {Hereditary ataxias are a heterogeneous group of neurodegenerative disorders characterized by impaired balance and coordination, often due to cerebellar dysfunction. Despite advances in identifying genetic causes, animal models remain essential for dissecting underlying mechanisms and testing therapeutic strategies. Here we describe a mouse model of spastic ataxia and myopathy caused by a missense mutation in Tuba4a (n.A626C, p.Gln176Pro). In an ENU mutagenesis screen, a male C57BL/6 J mouse exhibiting muscle wasting and an intention tremor starting at approximately 4 weeks-of-age was identified. The male was bred by in vitro fertilization to BALB/cByJ oocyte donors. Genetic mapping determined dominant inheritance and localized the mutation to Chromosome 1. Genome sequencing revealed single nucleotide polymorphisms (SNPs) in serine threonine kinase 36 (Stk36Y1003N) and alpha-tubulin 4A (Tuba4aQ176P) in the mapping interval. These SNPs were CRISPR-engineered into C57BL/6 J mice, which confirmed the Tuba4aQ176P variant as the causative mutation. Mutant mice are normal at 3 weeks, except for decrement in muscle response following repetitive nerve stimulation. However, by 30 days these mice have overt ataxia, Purkinje neuron degeneration, and extensive skeletal muscle defects, which contribute to a decreased lifespan. Dominant TUBA4A mutations in humans are associated with spastic ataxia type 11 (SPAX11), congenital myopathy type 26 (CMYO26), and frontotemporal dementia/amyotrophic lateral sclerosis type 9 (FTDALS9). Our mice exhibit hallmark features of SPAX11 and CMYO26, but do not show motor neuron degeneration. This specificity makes this model a valuable tool for studying cell-type selective effects of TUBA4A mutations in neurodegeneration and myopathy.},
}

Animals
Disease Models, Animal
Mice
Male
*Spinocerebellar Ataxias/genetics/pathology
*Muscle Spasticity/genetics/pathology
*Muscular Diseases/genetics/pathology
*Tubulin/genetics
Humans
*Intellectual Disability/genetics/pathology
*Optic Atrophy/genetics/pathology
Mice, Inbred C57BL
Mutation, Missense
Polymorphism, Single Nucleotide
Mutation
Genes, Dominant
Female
Protein Serine-Threonine Kinases/genetics
Muscle, Skeletal/pathology

@article {pmid42680415,
year = {2026},
author = {Wu, H and Zhou, Q and Fan, Z and Lao, Y and Pu, J and Wang, C and Chen, J and Huang, L and Song, S and Zhong, Y and Li, M and Pan, K and Ma, J},
title = {High carbon dioxide and silicon-aluminum interactions remodel cell walls: Surface architecture and adhesion in the marine diatom Phaeodactylum tricornutum.},
journal = {Journal of environmental sciences (China)},
volume = {168},
number = {},
pages = {571-578},
doi = {10.1016/j.jes.2026.01.023},
pmid = {42680415},
issn = {1001-0742},
mesh = {*Diatoms/physiology/drug effects ; *Silicon/chemistry/metabolism ; *Carbon Dioxide/toxicity ; *Aluminum/chemistry/toxicity ; *Cell Wall ; },
abstract = {Anthropogenic carbon dioxide (CO2) elevation increases pressure on ocean ecosystems. As the key primary producers in marine ecosystems, diatoms rely heavily on silicon (Si) to form their cell walls, while aluminum (Al) can compete with or modulate Si uptake. Nevertheless, the interactions among CO2, Si, and Al in marine diatoms remain unclear. This study elucidates how CO2, Si, and Al influence the model marine diatom Phaeodactylum tricornutum through single-element (C, Si, Al) and combined treatments (+Si+CO2, +Al+CO2). Multilevel indicators from growth rate to surface nano structures and elemental composition were characterized using interdisciplinary methods-such as atomic force microscopy and X-ray photoelectron spectroscopy. Results demonstrate that elevated CO2 and exogenous Si synergistically increased the growth rate of diatoms by 53 %, but the cell size significantly decreased by 5.4 %. Critically, this co-stimulation concurrently increased surface roughness and enhanced silicate polymerization via higher silanol groups (Si-OH) ratio in cell walls, thereby accelerating the sinking velocity. Al's impact emerged only under elevated CO2, promoting organic groups synthesis such as elevated amide-N functional groups on cell surfaces. These findings demonstrate that rising CO2, interacting with Si/Al availability, alters diatom adaptability and thereby potentially impacts diatom-mediated C-Si-Al biogeochemical cycles.},
}

*Diatoms/physiology/drug effects
*Silicon/chemistry/metabolism
*Carbon Dioxide/toxicity
*Aluminum/chemistry/toxicity
*Cell Wall

@article {pmid42680774,
year = {2026},
author = {Ren, K and Cheng, M and Luo, Q and Zhang, B and Zhang, H and Li, Z and Liu, Y and Wang, Y and Kang, T and Dai, X and Chen, J and Cheng, Y and Huang, L},
title = {YTHDC1 functions as a molecular chaperone to suppress ALS-linked hnRNPA1 mutants from aggregation.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42680774},
issn = {2041-1723},
support = {32300651//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82370182//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; *Heterogeneous Nuclear Ribonucleoprotein A1/genetics/metabolism/chemistry ; Humans ; *Molecular Chaperones/metabolism/genetics ; Animals ; Mutation ; Protein Aggregates ; Protein Folding ; Protein Aggregation, Pathological/genetics/metabolism ; *Nerve Tissue Proteins/metabolism/genetics ; Neurons/metabolism ; },
abstract = {Proteostasis failure drives multiple neurodegenerative disorders (NDs), and ATP-independent chaperone pathways that support neuronal proteostasis remain poorly defined. Here, we identify the N6-methyladenosine (m[6]A)-binding protein YTHDC1 as an ATP-independent molecular chaperone, whose activity is mediated by a highly acidic polyaspartate/glutamate (polyD/E) segment. YTHDC1 prevents protein misfolding and aggregation, unfolds kinetically trapped substrates, and resolubilizes pre-formed aggregates. Deletion of the polyD/E segment abolishes these activities, whereas aromatic-cage mutants retain chaperone activity, demonstrating independence from m[6]A recognition. We identify the amyotrophic lateral sclerosis (ALS)-associated RNA-binding protein hnRNPA1 as a YTHDC1 client. YTHDC1 maintains liquid-like hnRNPA1 condensates, delays fibrillization of disease-associated mutants, and limits stress-granule sequestration, while mitigating mutant hnRNPA1-induced neurite growth defects in primary neurons. These findings define a proteostatic function of YTHDC1 and highlight its chaperone activity as a potential target for mitigating protein aggregation in ALS-related NDs.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism
*Heterogeneous Nuclear Ribonucleoprotein A1/genetics/metabolism/chemistry
Humans
*Molecular Chaperones/metabolism/genetics
Animals
Mutation
Protein Aggregates
Protein Folding
Protein Aggregation, Pathological/genetics/metabolism
*Nerve Tissue Proteins/metabolism/genetics
Neurons/metabolism

@article {pmid42680797,
year = {2026},
author = {Lawandos, L and Sodhi, CP},
title = {Early CFTR modulation and clinical outcomes in preschool cystic fibrosis.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {42680797},
issn = {1530-0447},
abstract = {This commentary discusses Presti et al.'s multicenter prospective study evaluating lumacaftor/ivacaftor therapy in preschool children with cystic fibrosis homozygous for F508del. The findings provide important real-world evidence that early CFTR modulation improves biomarkers of CFTR function, pulmonary outcomes, and early lung physiology while maintaining an acceptable safety profile. These data support the broader concept that intervention during early childhood may offer an opportunity to modify disease progression before irreversible organ damage develops.},
}

@article {pmid42680877,
year = {2026},
author = {Ren, Q},
title = {Plasma biomarkers for ALS.},
journal = {Nature neuroscience},
volume = {29},
number = {9},
pages = {2056},
doi = {10.1038/s41593-026-02440-8},
pmid = {42680877},
issn = {1546-1726},
}

@article {pmid42670631,
year = {2026},
author = {Bischoff, KE and Leavell, YL and Besbris, JM and Lero, C and Noble, K and Grouls, A and Kurent, J and Kluger, BM and Pantilat, SZ and Mehta, AK and , },
title = {Priorities for Advancing Palliative Care for Amyotrophic Lateral Sclerosis: A Consensus Report From a Palliative Care for ALS Working Group in the United States.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70381},
pmid = {42670631},
issn = {1097-4598},
abstract = {Until there is a cure for amyotrophic lateral sclerosis (ALS), it is imperative that everyone facing this devastating illness receives care to alleviate symptoms and suffering and improve quality of life. Emerging evidence has demonstrated benefits of palliative care for people with ALS, but palliative care is not yet widely available or accessed by people with ALS throughout the disease course. The Palliative Care for ALS Working Group was formed within the International Neuropalliative Care Society, consisting of interprofessional ALS and palliative care clinicians, researchers, advocates, and patients and care partner representatives who are committed to improving palliative care for people living with ALS. The group engaged in a strategic planning process to determine what is needed to advance palliative care for people with ALS over the next 3-5 years. This report outlines the core recommendations from that strategic planning process. Recommendations are divided into five sections: (1) clinician education, (2) clinical service expansion, (3) research, (4) public awareness, and (5) policy change. The aim of this report is to provide ALS and palliative care clinicians, researchers, ALS advocacy organizations, and funders with a road map of priority areas where dedicated focus could significantly advance palliative care for people facing ALS, with the goals of relieving suffering and improving quality of life. The Palliative Care for ALS Working Group is making concrete steps toward these priority areas and will continue to serve as a convening and coordinating body for this work.},
}

@article {pmid42670660,
year = {2026},
author = {Basualdo Allende, AL},
title = {Comment on: 'Living in a world that's not about us': The impact of everyday life on the health and wellbeing of autistic women and gender diverse people.},
journal = {Women's health (London, England)},
volume = {22},
number = {},
pages = {17455057261484826},
pmid = {42670660},
issn = {1745-5065},
mesh = {Humans ; Female ; *Oral Health ; *Autistic Disorder/psychology ; *Women's Health ; Gender-Nonconforming Persons ; },
abstract = {This correspondence comments on Grove et al.'s autistic-led qualitative study on the health and wellbeing of autistic women and gender-diverse people. It argues that oral health should be considered within autism-aware women's healthcare because toothbrushing, dental attendance, oral pain, sensory distress, and communication barriers may affect daily living, access to care, and overall wellbeing. The letter proposes a practical integration pathway based on simple oral-health screening, autism-aware dental referral, sensory and communication adaptations, and collaboration with primary care, mental health, and women's health services. This approach does not imply causality, but supports more holistic, person-centred care.},
}

Humans
Female
*Oral Health
*Autistic Disorder/psychology
*Women's Health
Gender-Nonconforming Persons

@article {pmid42671301,
year = {2026},
author = {Burke, S and Skedros, SA and Carroll, BT},
title = {Comment on Dowdle et al.'s "National Trends in Repair Type Selection After Mohs Micrographic Surgery: A Benchmark Analysis Using TriNetX.".},
journal = {Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]},
volume = {},
number = {},
pages = {},
doi = {10.1097/DSS.0000000000005334},
pmid = {42671301},
issn = {1524-4725},
}

@article {pmid42671791,
year = {2026},
author = {Thomasen, MS and Brams, PH and Værbak, N and Cox, CMM and Parsons, CE},
title = {Daily emotion in fathers and mothers: Little evidence for greater paternal well-being during infant care.},
journal = {Emotion (Washington, D.C.)},
volume = {},
number = {},
pages = {},
doi = {10.1037/emo0001734},
pmid = {42671791},
issn = {1931-1516},
support = {//Carlsbergfondet/ ; },
abstract = {Parents' daily experience of childcare has garnered considerable attention following Kahneman et al.'s (2004) finding that childcare ranked among the least enjoyable daily activities. Subsequent studies have generally found that fathers report more positive valence during childcare compared to mothers. Here, we used experience sampling to examine daily experiences of first-time parents in Denmark between 2022 and 2024, where parental leave policies aim to promote involvement of fathers in infant care. Parents responded to 7 days of prompts during maternity and paternity leave, assessing valence (0-100 scale), sleepiness (Karolinska Sleepiness Scale), and current activities, including direct infant care, indirect care, and play (N = 227). Data were analyzed using Bayesian multilevel beta regression models. We found no credible evidence for the previously documented father advantage in valence during childcare. Mothers showed less positive valence during caregiving activities relative to other activities; effects for fathers were uncertain, and valence patterns differed across maternity and paternity leave. Sleepiness was strongly associated with less positive valence for both parents, with mothers showing steeper declines compared to fathers. Sleepiness moderated activity-valence associations in gender-specific ways: attenuating negative associations with direct care for mothers while reducing positive associations with play for fathers. In a country where paternal caregiving is supported through paid leave policies, mothers and fathers report largely similar valence patterns during infant care. The robust association between sleepiness and less positive valence points to sleep disruption as impacting parental emotion experiences, with mothers showing more vulnerability to its negative effects. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid42672036,
year = {2026},
author = {Krumina, M and Fernandes, S and Vilne, B and Baczyk, M},
title = {Computational Insights into Neuromodulation: How Electric Fields Shape Motor Neuron Excitability.},
journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TNSRE.2026.3729166},
pmid = {42672036},
issn = {1558-0210},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease characterized by the selective loss of spinal motor neurons (MN). Trans-spinal direct current stimulation (tsDCS) has emerged as a promising noninvasive neuromodulation technique that could provide neuroprotection and slow down disease progression. However, the mechanisms by which tsDCS affects individual MNs remain poorly understood. This study uses computational modeling to explore how low-intensity extracellular electric fields (EEFs), generated by tsDCS, influence the electrophysiological behavior of MNs. Morphologically realistic, multi-compartment models of neonate mouse alpha-MNs were developed in the NEURON simulation environment. Simulations were conducted under different EEF magnitudes, polarities and orientations. At the population level, consistent directional effects on excitability-related properties were limited and depended on stimulation condition. However, analyses of response magnitude showed that EEFs could modulate several properties, including resting membrane potential and rheobase, even when the direction of change varied across neurons. This heterogeneity was associated with neuronal morphology and its alignment with the applied field, with dendritic length and asymmetry affecting sensitivity. Overall, the results suggest that low-intensity EEFs produce modest, morphology-dependent modulation of MN electrophysiological properties, and that variability in neuronal structure and orientation may help explain discrepancies across previous experimental and modeling studies.},
}

@article {pmid42673727,
year = {2026},
author = {Aladwan, S and Jasim, A and Qassem, TA and Gajjar, TB and Hanumanthayya, M and Tripathi, V and Maharana, L and Bainsal, N},
title = {Human health risk assessment of toxic and non-toxic elements in various oily, cream, and powder cosmetics in Arab countries- A systematic literature review.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {97},
number = {},
pages = {127946},
doi = {10.1016/j.jtemb.2026.127946},
pmid = {42673727},
issn = {1878-3252},
abstract = {Oily, cream, and powder cosmetics (OCPCs) are widely used worldwide, especially in Arab nations, highlighting the need for ongoing heavy metal (HM) monitoring. This systematic review examined 16 HM concentrations in 14 OCPC product categories across 11 of the 22 Arab countries, selected countries based on predefined inclusion and exclusion criteria, and evaluated their associated health risks for only 9 of the 14 OCPCs for which sufficient data were available. The analysis included 24 papers published between June 1, 2007, and January 30, 2026, selected according to prescribed inclusion and exclusion criteria. International authorities like the WHO and the EU set acceptable limits (ALs) for HM levels. According to EPA criteria, all detected HMs underwent a health risk assessment (HRA). Saudi Arabia and Jordan had the highest HM detection rates in OCPCs among the 11 Arab countries analyzed, underscoring the need for stronger regulation. Moisturizing creams, toners, cosmetic masks, and oils were mostly contaminated with non-toxic HMs, whereas facial foundation and face cream samples were contaminated with toxic HMs. Despite exceedances of WHO and EU ALs for several elements, the EPA-based dermal risk indices remained below acceptable thresholds, reflecting the distinction between concentration-based regulatory limits and exposure-based health risk assessment. Arab regulatory agencies should establish monitoring systems to limit HMs in OCPCs, in line with WHO and EU guidelines on HM ALs in cosmetics, before market access.},
}

@article {pmid42674126,
year = {2026},
author = {Raffaele, S and Bonifacino, T and Mannella, FC and Nguyen, N and Torazza, C and Marangon, D and Chinosi, EM and Schrøder, HD and Hejbøl, EK and Madsen, K and Marchetti, L and Trincavelli, ML and Milanese, M and Lecca, D and Lambertsen, KL and Bonanno, G and Abbracchio, MP and Fumagalli, M},
title = {Selective targeting of the oligodendroglial GPR17 receptor improves myelin integrity and motor function in female SOD1[G93A] mice.},
journal = {Pharmacological research},
volume = {232},
number = {},
pages = {108424},
doi = {10.1016/j.phrs.2026.108424},
pmid = {42674126},
issn = {1096-1186},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no definitive disease-modifying therapies available, underscoring the urgent need to identify novel druggable targets. The G protein-coupled receptor GPR17 is a critical regulator of oligodendrocyte maturation and has emerged as a candidate target in ALS, yet its relevance to human disease and its therapeutic potential remain unclear. Here, we demonstrate that pathological GPR17 upregulation defines a conserved, pathologically immature oligodendroglial state in human ALS that can be pharmacologically leveraged to restore myelin integrity and improve functional outcome in vivo. Publicly available transcriptomics datasets and histological analyses revealed an increased abundance of GPR17-expressing immature oligodendrocytes in post-mortem human spinal cord tissue from ALS cases. Moreover, sustained activation of GPR17 with a selective agonist induced GPR17 internalization in heterologous expression systems and promoted the differentiation of primary oligodendrocyte precursors derived from SOD1[G93A] mice. Translating these findings in vivo, chronic treatment with a brain-penetrant GPR17 agonist derived from the same pharmacological class significantly extended survival, delayed body weight loss, and improved motor performance in female SOD1[G93A] mice, whereas male mice showed no therapeutic benefit. These effects were associated with restored oligodendrocyte maturation, preserved myelin integrity, motor neuron survival, and attenuated reactive gliosis in the spinal cord of female SOD1[G93A] mice, while milder effects were observed in males. Together, these findings establish oligodendroglial GPR17 as a conserved and pharmacologically actionable target in ALS and show that sustained in vivo GPR17 agonism can reprogram altered oligodendroglial states and slow disease progression in a sex-dependent manner.},
}

@article {pmid42675240,
year = {2026},
author = {Ma, S and Luo, S and Zhong, H},
title = {Artificial Intelligence in Neuromuscular Diseases: Opportunities for a Data-Scarce Field.},
journal = {Neurology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42675240},
issn = {2193-8253},
support = {Open research fund: gect-2025-Z01//Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases/ ; },
abstract = {Neuromuscular diseases (NMDs) encompass over 800 distinct entities affecting approximately one in 1000 individuals worldwide, with progressive muscle weakness, atrophy, and motor impairment as primary clinical manifestations. The rarity of most NMDs creates fundamental challenges for artificial intelligence (AI) and machine learning (ML) applications that typically require large-scale datasets. In this narrative review we synthesize the literature published between 2018 and 2025 on AI applications across the NMD spectrum, organized by clinical application domain. We examine how AI has advanced diagnostic capabilities through genetic variant interpretation, muscle magnetic resonance imaging analysis, electromyography-based classification, and computational pathology. In disease monitoring and prognosis, wearable-derived digital biomarkers have achieved regulatory qualification (US Food and Drug Administration [FDA] and European Medicines Agency [EMA]) as clinical trial endpoints for Duchenne muscular dystrophy, while AI-driven survival models for amyotrophic lateral sclerosis (ALS) have been validated across 14 European centers. Proteomic and multi-omics analyses using ML have identified diagnostic panels for ALS. However, most reported models were developed and internally validated on single-center datasets, and few have undergone external or prospective validation or clinical implementation. Despite these achievements, research intensity varies dramatically across NMD subtypes, with ALS and Duchenne muscular dystrophy dominating while myotonic dystrophy, congenital myopathies, and metabolic myopathies remain virtually unexplored. Critical gaps persist in computational pathology, multi-center validation, and clinical translation. In this review, we discuss how federated learning, international collaborative networks (TREAT-NMD, Solve-RD, EURO-NMD), and foundation models can address these challenges, and propose directions for future AI-enhanced clinical studies in this data-scarce field.},
}

@article {pmid42676114,
year = {2026},
author = {Xu, J and Wu, X and Zhang, B and Wu, K},
title = {Ba4Al4SnS12: balancing bandgap and nonlinear optical performance in thioaluminate via multifunctional group engineering.},
journal = {Dalton transactions (Cambridge, England : 2003)},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6dt01763k},
pmid = {42676114},
issn = {1477-9234},
abstract = {The exploration of infrared nonlinear optical (IR NLO) crystals with excellent performance has attracted increasing attention in view of the inherent drawbacks (low laser damage threshold (LDT) or harmful two-photon absorption (TPA)) of commercial NLO crystals. However, the critical performances (wide bandgap (>3.0 eV) and good nonlinearity (>0.5 × AgGaS2)) show an inverse relationship in IR NLO crystals; thus, the judicious selection and combination of functional motifs are critical, as performance is fundamentally governed by structure. For that reason, we propose a multifunctional group engineering strategy incorporating [AlS4] for a wide bandgap and [SnS4] for large nonlinearity to design a new NLO chalcogenide that affords the successful synthesis of thioaluminate, Ba4Al4SnS12. Experimental study shows that Ba4Al4SnS12 achieves an optimal performance balance between a wide bandgap (3.06 eV) and a moderate second-harmonic generation (SHG) response (0.56 × AgGaS2) with requisite phase-matching behavior (Δn = 0.042), further indicating that Ba4Al4SnS12 could be regarded as a potential IR NLO candidate. Theoretical analysis demonstrates the respective contributions of distinct tetrahedral groups to the bandgap and NLO coefficient and validates the feasibility of multifunctional group engineering. Therefore, this study provides a principle for selecting excellent functional groups and research systems, illuminating a feasible pathway toward future NLO crystals with superior performance.},
}

@article {pmid42676195,
year = {2026},
author = {Arbuzova, EE and Seksyaev, NE and Karakulova, YV and Selyanina, NV and Danilova, MA},
title = {[Atypical forms of amyotrophic lateral sclerosis].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {126},
number = {8},
pages = {13-20},
doi = {10.17116/jnevro202612608113},
pmid = {42676195},
issn = {1997-7298},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/classification ; Phenotype ; Diagnosis, Differential ; Disease Progression ; Motor Neurons/pathology ; },
abstract = {This article provides a comprehensive overview of contemporary concepts regarding the classical and atypical phenotypes of amyotrophic lateral sclerosis (ALS), with a particular focus on critical diagnostic challenges. The classical variant of the disease is characterized by the progressive involvement of both upper and lower motor neurons, typically presenting with an asymmetric onset and a predictable progression. However, several atypical phenotypes are identified, including syndromes predominantly affecting the lower motor neurons, such as the «hanging hands» and «hanging legs» syndromes, isolated bulbar paralysis, ALS with respiratory onset, and forms with a predominance of upper motor neuron involvement. These atypical variants often mimic other neurological conditions-such as cervical myelopathy, multifocal motor neuropathy, and myasthenia gravis-which can result in significant delays in the accurate diagnosis of ALS. Atypical forms of ALS represent a major source of diagnostic errors in clinical practice. Enhancing healthcare professionals' understanding of the spectrum of phenotypic presentations, alongside the application of contemporary diagnostic criteria, facilitates more timely diagnoses, optimized patient care pathways, and the prompt initiation of pathogenetic therapies, ultimately improving both survival rates and quality of life for affected individuals.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology/classification
Phenotype
Diagnosis, Differential
Disease Progression
Motor Neurons/pathology

@article {pmid42677779,
year = {2026},
author = {Ali, A and Arif, M and Ashraf, U and Elahi, S and Mustafa, A and Yasir, MB and Sarfraz, W and Ansari, AU and Masood, HMY and Shabbir, MA and Abdullah, A and Sharma, MK},
title = {CSF Tau and Amyloid Biomarkers in Cognitive Impairment Across the ALS-FTD Spectrum: A Systematic Narrative Review and Evidence Map.},
journal = {Brain and behavior},
volume = {16},
number = {9},
pages = {e71740},
pmid = {42677779},
issn = {2162-3279},
mesh = {Humans ; *tau Proteins/cerebrospinal fluid ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid/complications ; Biomarkers/cerebrospinal fluid ; *Frontotemporal Dementia/cerebrospinal fluid/complications ; *Amyloid beta-Peptides/cerebrospinal fluid ; *Cognitive Dysfunction/cerebrospinal fluid/etiology ; },
abstract = {INTRODUCTION: Cognitive impairment is an important non-motor manifestation of amyotrophic lateral sclerosis (ALS), particularly across the ALS-frontotemporal dementia (ALS-FTD) spectrum. Cerebrospinal fluid (CSF) tau and amyloid biomarkers may reflect nonspecific neurodegenerative injury, concomitant Alzheimer disease (AD) pathology, or distinct cognitive phenotypes. However, available evidence remains limited, fragmented, and methodologically heterogeneous.

METHODS: This systematic narrative review and semi-quantitative evidence map was conducted according to PRISMA 2020 recommendations. PubMed, Scopus, Web of Science, and Google Scholar were searched from database inception through May 2026. Eligible observational studies reported cognition-specific associations between CSF tau, amyloid, or related neurodegenerative biomarkers and cognitive outcomes in ALS-spectrum populations. Two reviewers independently screened studies, extracted quantitative effect estimates, and assessed risk of bias using the Newcastle-Ottawa Scale. Cross-study consistency was summarized using an exploratory semi-quantitative evidence-coding framework.

RESULTS: Four observational studies comprising 638 ALS-spectrum participants fulfilled the eligibility criteria. Total tau and p-tau181 showed the most reproducible associations with cognition. Total tau correlated with ECAS total (r = -0.398, P < 0.001) and ALS-specific cognition (r = -0.403, P < 0.001), while adjusted multicenter analyses demonstrated associations between p-tau181 and ECAS total (β = -0.03, p = 0.006) and memory performance (β = -0.04, p = 0.003). Both biomarkers received ++ evidence-map coding. Amyloid findings were more heterogeneous; lower Aβ42/Aβ40 was associated with poorer memory performance (β = 0.20, p = 0.044), but continuous amyloid-cognition associations were not consistently replicated across cohorts (± evidence). Broader CSF protein-ratio findings remained exploratory. Clinical, cognitive, assay, and analytical heterogeneity precluded meta-analysis.

CONCLUSIONS: The available evidence, although limited and heterogeneous, suggests that total tau may primarily reflect broader neurodegenerative injury, whereas p-tau181 and Aβ42/Aβ40 may be more informative for selected cognitive phenotypes or possible AD co-pathology. These biomarkers should remain research tools until larger, standardized, longitudinal multicenter studies establish their pathological specificity, predictive value, and clinical utility.},
}

Humans
*tau Proteins/cerebrospinal fluid
*Amyotrophic Lateral Sclerosis/cerebrospinal fluid/complications
Biomarkers/cerebrospinal fluid
*Frontotemporal Dementia/cerebrospinal fluid/complications
*Amyloid beta-Peptides/cerebrospinal fluid
*Cognitive Dysfunction/cerebrospinal fluid/etiology

@article {pmid42677823,
year = {2026},
author = {Chandran, D and Agrawal, U and Damayanthi, D and Nair, DT and Mandagini, G and Nair, SS and Narasimhaiah, D and Fernandez, FB and Thakur, P and Raghavan, CT and Krishnan, S and Gopala, S and Urulangodi, M},
title = {Cofilin 1 Is an Extracellular Vesicle-Associated Plasma Biomarker of Parkinson's Disease in Humans.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78348},
pmid = {42677823},
issn = {1531-8249},
abstract = {OBJECTIVE: Parkinson's disease (PD) lacks reliable, minimally invasive biomarkers for diagnosis. This study aimed to identify and validate PD-specific plasma extracellular vesicle (EV)-associated proteins.

METHODS: Plasma EVs were isolated by ultracentrifugation and characterized. Proteomic profiling of total plasma EVs from PD patients and healthy controls was performed, and a candidate protein identified after analysis was validated by enzyme-linked immunosorbent assay. Diagnostic accuracy was evaluated using receiver operating characteristic and precision-recall curve analysis. Disease specificity was examined in progressive supranuclear palsy and amyotrophic lateral sclerosis. Histochemical and immunofluorescence analyses were conducted in human and mouse PD brain tissue.

RESULTS: Proteomic analysis identified distinct PD-specific EV proteins, including cofilin 1 (CFL1), which was significantly enriched in EVs isolated from PD. EV-CFL1 levels were significantly elevated in PD compared with healthy controls (p < 0.0001). Receiver operating characteristic analysis showed strong diagnostic performance for EV-CFL1 (area under the curve 0.87). Also, EV CFL1 levels could distinguish PD from progressive supranuclear palsy patients (area under the curve 0.914). CFL1 was enriched in L1 cell adhesion molecule-positive EVs, indicating a possible neuronal origin. CFL1 was detected in both human and mouse PD brain sections. Importantly, EV-CFL1 levels were independent of age, disease stage, and motor severity.

INTERPRETATION: EV-associated CFL1 represents a PD-specific, blood-based marker with strong diagnostic accuracy and can distinguish PD from atypical parkinsonism. The presence of CFL1 was confirmed in human and mouse PD brain tissue, and its accumulation in PD brain suggests a possible role in disease pathogenesis. ANN NEUROL 2026.},
}