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Temporal Adversarial Attacks on Time Series and Reinforcement Learning Systems: A Systematic Survey, Taxonomy, and Benchmarking Roadmap
Ade Kurniawan
,Merios Gusan Putra
,Dani Lukman Hakim
,Mochammad Ariyanto
Posted: 08 January 2026
Programmed Cell Death 1 Ligand 1 Is Essential for Electroacupuncture Mediated Analgesia in the Cerebellum of Fibromyalgia Mice
Hung-Yu Huang
,Younbyoung Chae
,Ming-Chia Lin
,I-Han Hsiao
,Hsin-Cheng Hsu
,Chien-Yi Ho
,Yi-Wen Lin
Posted: 08 January 2026
Toward Integrated Water Resource Strategies in Taiwan: A Cross-Disciplinary Review of Hydrological Variability, Infrastructure Design, and Cultural-Ecological Integration
Ching Ruey (Edward) Luo
Posted: 08 January 2026
User Authentication Using Inner Wrist Skin Prints: Feasibility and Performance Assessment with Off-the-Shelf Fingerprint Sensor
Szymon Cygan
,Patryk Lamprecht
,Jakub Żmigrodzki
,Jan Łusakowski-Milencki
,Nikolaos Simopulos
,Adrian Zarycki
,Piotr Muranty
Posted: 08 January 2026
A Mechanical Formulation for Resistive Network Analysis: The Spring-Conductance Matrix Method
Faiçal Barzi
,Kaoutar Fethi
Posted: 08 January 2026
Integrated Functional and Structural Analysis of Eleven CYP21A2 Variants of Uncertain Significance Resolves Their Pathogenic Role in Congenital Adrenal Hyperplasia
Yingtong Xu
,Anna Matveeva
,Flemming Steen Jørgensen
,Amit Pandey
Context: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired cortisol and aldosterone synthesis. While genotype-phenotype correlations are well-established for common CYP21A2 mutations, the clinical significance of rare missense variants remains a challenge, often leading to their classification as Variants of Uncertain Significance (VUS) and complicating genetic counseling. Objective: To determine the functional impact and pathogenicity of eleven CYP21A2 variants (p.L10del, p.R76K, p.E162G, p.S274Y, p.L308V, p.S373N, p.P387L, p.H393Q, p.R401G, p.R436C, and p.S494N) utilizing a comprehensive approach integrating population genetics, in silico structural modeling, and in vitro functional assays. Methods: Allele frequencies were analyzed using global databases (gnomAD, 1000G). Evolutionary conservation was assessed via ConSurf, and thermodynamic stability was predicted using FoldX and DUET. Structural dynamics were simulated using Molecular Dynamics (MD) (100 ns). Variants were expressed in HEK293T cells, and enzymatic activity was quantified using radiolabeled progesterone and 17-hydroxyprogesterone (17-OHP) as substrates, normalized to protein expression levels determined by Western blot. Results: Population analysis identified p.L10del and p.S494N as common polymorphisms (allele frequencies >5% in specific populations) with near-normal enzymatic activity (~99% and ~67% for 17-OHP, respectively), supporting a Benign classification. Conversely, p.L308V, p.P387L, and p.R436C were ultra-rare and exhibited severe loss of function, retaining <20% of wild-type activity for 17-OHP. Structural modeling revealed that p.L308V causes steric clashes in the conserved I-helix, while p.P387L induces core destabilization and kinetic instability. p.R436C disrupts the surface hydrogen-bond network essential for P450 Oxidoreductase interaction. These variants are reclassified as Pathogenic, likely associated with Simple Virilizing CAH. Variants p.H393Q and p.R401G showed moderate impairment (~40–45% activity), consistent with a Likely Pathogenic status and Non-Classic CAH phenotype. Conclusions: This study resolves the diagnostic status of eleven CYP21A2 variants. We provide definitive evidence that p.L308V is a severe pathogenic missense mutation distinct from frameshift alleles at the same locus, and that surface mutations like p.R436C can be as deleterious as core mutations due to the disruption of redox partner interfaces. These findings refine the genetic classification of CAH, enabling precise diagnosis and personalized management for affected families.
Context: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired cortisol and aldosterone synthesis. While genotype-phenotype correlations are well-established for common CYP21A2 mutations, the clinical significance of rare missense variants remains a challenge, often leading to their classification as Variants of Uncertain Significance (VUS) and complicating genetic counseling. Objective: To determine the functional impact and pathogenicity of eleven CYP21A2 variants (p.L10del, p.R76K, p.E162G, p.S274Y, p.L308V, p.S373N, p.P387L, p.H393Q, p.R401G, p.R436C, and p.S494N) utilizing a comprehensive approach integrating population genetics, in silico structural modeling, and in vitro functional assays. Methods: Allele frequencies were analyzed using global databases (gnomAD, 1000G). Evolutionary conservation was assessed via ConSurf, and thermodynamic stability was predicted using FoldX and DUET. Structural dynamics were simulated using Molecular Dynamics (MD) (100 ns). Variants were expressed in HEK293T cells, and enzymatic activity was quantified using radiolabeled progesterone and 17-hydroxyprogesterone (17-OHP) as substrates, normalized to protein expression levels determined by Western blot. Results: Population analysis identified p.L10del and p.S494N as common polymorphisms (allele frequencies >5% in specific populations) with near-normal enzymatic activity (~99% and ~67% for 17-OHP, respectively), supporting a Benign classification. Conversely, p.L308V, p.P387L, and p.R436C were ultra-rare and exhibited severe loss of function, retaining <20% of wild-type activity for 17-OHP. Structural modeling revealed that p.L308V causes steric clashes in the conserved I-helix, while p.P387L induces core destabilization and kinetic instability. p.R436C disrupts the surface hydrogen-bond network essential for P450 Oxidoreductase interaction. These variants are reclassified as Pathogenic, likely associated with Simple Virilizing CAH. Variants p.H393Q and p.R401G showed moderate impairment (~40–45% activity), consistent with a Likely Pathogenic status and Non-Classic CAH phenotype. Conclusions: This study resolves the diagnostic status of eleven CYP21A2 variants. We provide definitive evidence that p.L308V is a severe pathogenic missense mutation distinct from frameshift alleles at the same locus, and that surface mutations like p.R436C can be as deleterious as core mutations due to the disruption of redox partner interfaces. These findings refine the genetic classification of CAH, enabling precise diagnosis and personalized management for affected families.
Posted: 08 January 2026
Raw Milk Cheese Microbiomes: A Paradigm for Interactions of Lactic Acid Bacteria in Food Ecosystems
Christine Kate Olupot
,Olivia Sheehan
,Zoe Kampff
,Brian McDonnell
,David F. Woods
,Gabriele Andrea Lugli
,Marco Ventura
,F. Jerry Reen
,Douwe van Sinderen
,Jennifer Mahony
While industrial scale dairy fermentations often employ pasteurized milk as the substrate, many farmhouse and traditional production practices apply raw milk derived from a variety of mammals. Certain artisanal production systems rely on the autochthonous microbiota of the milk, fermentation vessels, equipment and/or environment to initiate milk coagulation. While the technological properties of lactic acid bacteria associated with dairy fermentations are well described, their interactions with other organisms during fermentation and cheese ripening are poorly investigated. This study presents an overview of the microbial ecology of raw and pasteurized milk used in the production of cheeses. Furthermore, we report on the motility phenotype, lactose utilization ability and metabolic products of isolates of Hafnia paralvei and Hafnia alvei, and determine that these strains could grow in a non-antagonistic manner on plates with strains of Lactococcus lactis and Streptococcus thermophilus. As artisanal and farmhouse production systems are often associated with protected or regionally significant products, it is essential to develop a clear understanding of the microbial communities within and the complex relationships between the community members.
While industrial scale dairy fermentations often employ pasteurized milk as the substrate, many farmhouse and traditional production practices apply raw milk derived from a variety of mammals. Certain artisanal production systems rely on the autochthonous microbiota of the milk, fermentation vessels, equipment and/or environment to initiate milk coagulation. While the technological properties of lactic acid bacteria associated with dairy fermentations are well described, their interactions with other organisms during fermentation and cheese ripening are poorly investigated. This study presents an overview of the microbial ecology of raw and pasteurized milk used in the production of cheeses. Furthermore, we report on the motility phenotype, lactose utilization ability and metabolic products of isolates of Hafnia paralvei and Hafnia alvei, and determine that these strains could grow in a non-antagonistic manner on plates with strains of Lactococcus lactis and Streptococcus thermophilus. As artisanal and farmhouse production systems are often associated with protected or regionally significant products, it is essential to develop a clear understanding of the microbial communities within and the complex relationships between the community members.
Posted: 08 January 2026
Cell‐Free Supernatant of Bacillus subtilis Suppresses the Mycelial Growth of Penicillium expansum by Destroyed the Cell Membrane Integrity and Provoke Cell Death
Huanhuan Li
,Yage Chen
,Zhipeng Xie
,Qian Su
,Bingqi Chen
,Yue Yang
,Guifang Ma
,Yizhu Yang
,Xinwen Shan
,Junjie Wang
+2 authors
Posted: 08 January 2026
Modified Lagrange-Jacobi Functions
Gaotsiwe Joel Rampho
Posted: 08 January 2026
From Linear ω-γ Correlation to Redshift-Dependent Dynamics: A Complete Phenomenological Framework and Testing Roadmap for Dark Energy
Tongfeng Zhao
Posted: 08 January 2026
Metal-Chelating Macroalgal Extract as a Marine Antioxidant for Stabilizing DHA Nanoemulsions
Sakhi Ghelichi
,Behdad Shokrollahi Yancheshmeh
,Mona Hajfathalian
,Seyed Hossein Helalat
,Arpan Shrestha
,Saroj Katwal
,Charlotte Jacobsen
Posted: 08 January 2026
Single Channel Slow Moving Target Detection Method for Terahertz Video Synthetic Aperture Radar Based on Shadows and Spots
Xiaofan Li
,Shuangxun Li
,Bin Deng
,Qiang Fu
,Hongqiang Wang
Posted: 08 January 2026
Membrane Dysfunction as a Central Mechanism in LRRK2-Associated Parkinson’s Disease: Comparative Analysis of G2019S and I1371V Variants
Khushboo Singh
,Roon Banerjee
,Chandrakanta Potdar
,Anisha Shaw
,Rakshith V
,Nitish Kamble
,Vikram Holla
,Ravi Yadav
,Pramod Kumar Pal
,Indrani Datta
Posted: 08 January 2026
Automated Videotopography for Dry Eye Diagnostics: Analytical Performance, Spatial Dynamics, and a Novel Multivariate Model
Daniela Oehring
Posted: 08 January 2026
A Paradigm Shift in Optical Precision Measurement for Space Technology: Falsification of the Equivalence Principle for Photons Resulting in the Concept of a Real Velocity Measuring Device (RVMD)
Etienne Brauns
Posted: 08 January 2026
Extracting Heart-Rate Variability Indicators from Wi-Fi CSI: A Pilot Correlation Study
Saurav Chaudhari
,Ketan Pise
,Dinesh Fukate
,Shantanu Gawande
Posted: 08 January 2026
Topographic Influence on Cold-Air Pool Formation: A Case Study of the Eiras Valley (Coimbra, Portugal)
António Rochette Cordeiro
,André Lucas
,José Miguel Lameiras
Posted: 08 January 2026
Demographic Associations with GPS-Inferred Routine Activity Spaces: Data from the Everyday Environments and Experiences (E3) Study
Nathan Ryder
,Ulf Bronas
,Jason Westra
,Jieqi Tu
,Evan De Jong
,Yosef Bodovski
,Kiarri N. Kershaw
,Nathan L. Tintle
Posted: 08 January 2026
Equity in Physical Activity Interventions to Promote Health: A Scoping Review of Trials
Lysanne Veerle Michels
,Lucy Smith
,Jacob Keast
,Hajira Dambha-Miller
Posted: 08 January 2026
Perimetry of the Central Visual Field Using a Head-Mounted Open-Source Perimeter in Patients with Inherited Retinal Diseases
Cord Huchzermeyer
,Friedrich Kruse
,Jan Kremers
Posted: 08 January 2026
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