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Whole-Genome Deep Learning Predicts Chemotherapy Response in Colorectal Cancer.

Chemotherapy response in colorectal cancer (CRC) exhibits significant heterogeneity, with current clinical predictors failing to capture complex genomic determinants of resistance. We developed a hybrid deep learning framework integrating convolutional neural networks (CNNs) and bidirectional long short-term memory (BiLSTM) networks to analyze whole-genome somatic mutations, evolutionary conservation, chromatin accessibility, and 3D genome architecture in 2,546 TCGA patients. An attention mechanism identified predictive genomic regions. The model achieved an AUC of 0.92 (95% CI: 0.89-0.94) in cross-validation and 0.88 (95% CI: 0.85-0.91) in independent validation, outperforming clinical models (&#x394;AUC = +0.18, p < 0.001). Key predictors included non-coding variants in TP53, KRAS, and PIK3CA regulatory regions. Triple-positive patients (mutations in all 3 regions) had significantly worse progression-free survival (HR = 4.7, p < 0.001). Our framework enables accurate chemotherapy response prediction and reveals novel non-coding resistance mechanisms, advancing precision oncology in CRC.

Humans

Pilot Distractions and Interruptions in Airlines: Ranking of Sources by Analytic Hierarchy Process.

ObjectiveThis work establishes a methodological framework for sources of pilot distraction and interruptions in a structured model that can be used as a tool for cockpit design/procedure assessment.BackgroundPilots must complete complex tasks, and distractions can impair performance and lead to errors that can cause aircraft accidents. Although various cockpit distractors are examined individually, there is no integrated approach.MethodDistraction and interruption sources were identified through a literature review and confirmed/extended by interviews with airline pilots. Associated weights were determined through pairwise comparisons, yielding a hierarchical model using the Analytic Hierarchy Process.Results26 sources of pilot distraction and interruptions were quantified and categorized into four categories: communication, head-down time, responding to abnormal conditions & unexpected situations, and searching for traffic.ConclusionA taxonomic structure for assessment is achieved with the top 5 sources identified as communications, technical interruptions, experience in type, environmental factors, operational irregularities, and airspace high terrain, accounting for 63.07%.ApplicationThe structured system is a flexible assessment scale that provides a taxonomic framework for airline risk management, supports future research, and cockpit design efforts.

Humans

Detoxifying biotransformation of chloramphenicol by Exiguobacterium sp. CAP4 and its bioaugmentation of chloramphenicol biodegradation in simulated wastewater.

The extensive use of chloramphenicol (CAP) in livestock leads the accumulation of CAP in livestock manures, threatening environmental and human health. Therefore, eliminating or reducing CAP concentration in manures before its re-utilization and application through microbial remediation is necessary. Exiguobacterium sp. CAP4, isolated from the plastisphere in duck manures, was capable of degrading CAP with the biodegradation efficiency of 97.8 % at initial CAP concentration of 5 mg/L within 4 days. A total of twenty-four biotransformation products were determined, including two novel transformation products, TP166 and TP203, enriched the integrity of CAP biodegradation pathways. Furthermore, the biotransformation process was proposed as a detoxifying process through biotransformation products toxicity evaluation. Notably, Exiguobacterium sp. CAP4 successfully colonized in the cow manures after inoculation, and bioaugmented the biodegradation of CAP in virgin cow manures. This study significantly extended our understanding of the CAP biotransformation fate, and provided a promising bacterial strain for bioremediation of CAP containing wastewater in situ.

Chloramphenicol

Extended Reality Interventions for Osteoarthritis of the Knee and Recovery After Total Knee Arthroplasty: Systematic Review and Meta-Analyses.

BACKGROUND: Nonpharmacologic interventions are important for treating knee pain due to osteoarthritis or after total knee arthroplasty (TKA), and extended reality (XR) technology may enhance treatments for these indications. OBJECTIVE: This systematic review aimed to evaluate XR interventions for pain due to knee osteoarthritis (KOA) or for recovery after TKA. METHODS: Databases were searched through May 2023 and updated in December 2025. Eligible trials evaluated XR interventions to treat KOA pain or after TKA. We classified interventions by depth of immersion and clinical mechanism. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria to determine the certainty of evidence for prioritized outcomes. Meta-analyses were performed when &#x2265;3 studies evaluated similar comparisons, outcomes, and time points. RESULTS: Eligible trials addressed KOA (k=12) or recovery after TKA (k=9). Sample sizes ranged from 36 to 306 participants, and most studies had a follow-up of &#x2264;3 months. Nineteen studies assessed pain-related functioning and pain intensity, and 5 assessed adverse events (AEs). For KOA, 10 studies examined interactive digital rehabilitation (IDR), and 2 examined virtual reality (VR)-digitally augmented exercise (DAE). IDR for KOA may result in better pain-related functioning (low certainty of evidence [COE]; pooled standardized mean difference [SMD] -0.59, 95% CI -1.11 to -0.06; prediction interval [PI] -1.72 to 0.55; k=5) and lower pain intensity at 6-8 weeks (low COE; pooled SMD -0.46, 95% CI -0.92 to 0.00; PI -1.39 to 0.47; k=4). VR-DAE for KOA (k=2) produced inconsistent results (very low COE). For post-TKA studies, 5 examined IDR, 2 examined VR-DAE, 1 examined VR-distraction, and 1 examined VR-psychoeducation. Post-TKA IDR may result in better pain-related functioning (low [k=4] and moderate COE [k=1]) but little to no difference in pain intensity (low-moderate COE; pooled SMD at 3-4 months -0.12, 95% CI -0.75 to 0.52; PI -1.63 to 1.27; k=3). VR-psychoeducation probably results in lower pain at 4 weeks (moderate COE; k=1), and VR-distraction may result in 6 months (low COE; k=1), whereas VR-DAE produced mixed findings (k=2; very low COE). IDR was not associated with AEs, and VR may not be associated with AEs for KOA (high and low COE), though AE reporting was uncommon (k=5) and evidence was very uncertain for post-TKA. CONCLUSIONS: IDR may augment treatment for KOA and post-TKA recovery, and VR may benefit post-TKA rehabilitation. This review is the first to stratify by level of immersion, clinical mechanism, and follow-up duration and to systematically evaluate AEs. IDR may be ready for integration into KOA care, while use after TKA needs more evidence. Randomized controlled trials with implementation outcomes could determine how XR interventions can be used for KOA, whereas trials evaluating efficacy and AEs are needed before their use for post-TKA.

Humans

Urban Design Quality and Clinical Mental Health: A Systematic Review.

ObjectivesThis systematic review synthesizes empirical evidence on core urban design dimensions that affect clinical mental health outcomes and examines how environmental exposures mediate or moderate these relationships.BackgroundUrban design has increasingly been recognized as a determinant of psychological well-being, yet a standardized framework to evaluate its mental health impact remains underdeveloped.MethodsFollowing PRISMA 2020 guidelines, we systematically reviewed 19 quantitative empirical studies published through January 2025, examining relationships between outdoor urban design features and validated clinical mental health indicators across four major databases.ResultsFindings reveal that urban design influences clinical mental health outcomes (depression, anxiety, stress, cognitive decline) through two objective spatial scales: street-level features (imageability, enclosure, human scale, complexity) and neighborhood environments (land use mix, density, green infrastructure). Environmental exposures (traffic, noise, air pollution) operate as perceptual and experiential mechanisms that mediate or moderate the mental health effects of these spatial design features.ConclusionsWe propose an integrated three-domain conceptual framework distinguishing objective spatial design scales from subjective exposure mechanisms. This framework provides evidence-based guidance for urban planners and policymakers toward creating mentally healthier urban environments.

Humans

Transcriptomic insights into the molecular mechanism of antifouling agent-induced settlement inhibition in the Pacific oyster Crassostrea gigas.

Marine biofouling remains a persistent challenge to maritime industries and marine ecosystems worldwide. In this study, we systematically evaluated the acute toxicity, settlement inhibitory efficacy, and underlying molecular mechanisms of an N-oleyl-1,3-propanediamine-based antifouling agent using pediveliger larvae of the Pacific oyster Crassostrea gigas. The 96&#xa0;h-LC50 of the agent was determined to be 0.81&#xa0;mg/L, and exposure to 1.68&#xa0;mg/L achieved complete larval settlement inhibition without inducing significant acute toxicity. Transcriptomic analysis identified 791 differentially expressed genes, dominated by downregulated genes associated with ribosomal function, translation, cell adhesion, and cytoskeletal organization. The agent exerts its inhibitory effect primarily through the global suppression of protein synthesis, disruption of cell-substrate adhesion and cytoskeletal integrity, and induction of proteotoxic stress responses. These findings reveal a multi-pathway molecular mechanism underlying antifouling agent-induced settlement inhibition in oyster larvae and provide key molecular biomarkers to support the development of eco-friendly antifouling technologies.

Animals

Furanic compounds in different coffee extraction systems: Analysis of the main influencing factors and correlation with acrylamide.

This study investigates how different coffee types representative of distinct roast profiles and brewing methods jointly affect the occurrence of furanic compounds and acrylamide in brewed coffee. Coffees were prepared using eight extraction methods (AeroPress, Clever, Chemex, French Press, Moka, Pure Brew, Turkish and V60). Five furanic compounds (furfural, furfuryl acetate, 5-methylfurfural, furfuryl alcohol and 5-hydroxymethylfurfural) were quantified in coffee powders and brews by HS-SPME-GC-MS, while acrylamide was determined by UHPLC-MS/MS. Moka and Turkish brews consistently exhibited the highest concentrations of furanic compounds, whereas paper-filtered pour-over methods (V60 and Chemex) showed the lowest levels. Pearson correlation analysis revealed coffee-dependent relationships between furanic compounds, acrylamide and extraction parameters with the strongest associations observed in dark-roasted coffee, reflecting advanced Maillard reaction chemistry. Overall, these results demonstrate that contaminant levels arise from the combined effects of intrinsic coffee chemistry and brewing mechanics and support targeted mitigation strategies: such as roast selection and brewing method optimization.

Acrylamide

Comprehensive study on pesticide residues and mycotoxins in freeze-dried strawberries and raspberries.

Freeze-dried fruit has gained popularity because it preserves the flavour and nutritional value of fresh fruit while providing extended shelf life. Despite this, there are concerns regarding its chemical safety. This study evaluated 58 freeze-dried fruit products from the Czech retail market, focusing on potential contamination. Pesticide residues and mycotoxins were determined using LC-MS/MS and GC-MS/MS. Overall, 111 pesticide residues (or their metabolites) and 3 mycotoxins were quantified. After applying processing factors, 12 pesticide residues exceeded EU maximum residue limits. Prohibited substances, including carbofuran, omethoate, and haloxyfop, were detected. Tenuazonic acid was found in 71% of samples, while alternariol and tentoxin were detected less frequently. More than half (54%) of strawberry samples contained 10 or more pesticide residues, indicating potential cumulative exposure concerns, particularly for children with lower body weight. These findings highlight the need for continued monitoring of freeze-dried fruits and further assessment of dietary exposure.

Pesticide Residues

Machine learning-ready genomic biomarkers: ATF3 polymorphisms predict postoperative analgesic demand through AI-compatible phenotyping.

PURPOSE: To determine whether ATF3 polymorphisms can serve as genetic biomarkers for machine learning-based precision analgesia by establishing a genotype-phenotype association suitable for predictive modeling of postoperative opioid requirements. METHODS: In a prospective cohort of 167 adults undergoing abdominal surgery, ATF3 SNPs rs3122721 and rs3125293 were genotyped. A structured dataset architecture was developed to represent genetic profiles as input features for supervised learning models, enabling translational analysis of genotype&#x2011;dependent opioid consumption over 72&#xa0;h. RESULTS: Patients with homozygous genotypes of the ATF3 SNPs had significantly higher opioid requirements than non&#x2011;carriers, despite reporting similar subjective pain scores. This consistent genotype&#x2011;dependent pattern provided a clinically relevant phenotype suitable for integration into predictive algorithms. CONCLUSION: ATF3 genotyping offers a promising biomarker for computationally informed precision analgesia. By linking genomic variability to clinically meaningful outcomes within a structured clinical and genomic framework, this approach supports the future development of risk-stratified clinical decision-support systems to optimize postoperative pain management.Trial registration ChiCTR1900021991, registered 30 April 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13755-026-00480-9.

ATF3

Insights into the regulation of the HOTAIR proximal promoter.

HOTAIR (HOX transcript antisense RNA) is a HOXC-cluster long intervening non-coding RNA (lincRNA) whose cancer relevance is tightly coupled to how its transcription is wired into hormone, hypoxia, inflammatory, and developmental signaling. HOTAIR is known to associate with cancer cell proliferation, motility, tumor invasion, and metastasis. The present mini-review focuses on the regulatory architecture and mechanistic complexity of HOTAIR transcriptional regulation, with emphasis on three organizing principles. First, we consider the impact of promoter choice between a canonical proximal promoter (P1), which supports the 2.2-2.4 kb transcript, and an alternative upstream promoter/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer-promoter communication between HOTAIR distal enhancer and P1/P2. Third, we summarize the recent epigenetic and epi-transcriptomic mechanisms involved in HOTAIR transcript initiation and elongation. A combination of these events determines isoform-specific transcription to govern cell-type-, context-, and cancer specific modulation of HOTAIR expression that promotes tumor formation and cancer progression. Finally, the review proposes how large-scale RNA datasets, long-read sequencing, and isoform-specific studies can refine our understanding of this versatile lincRNA's regulation.

Humans

Heat stress in cereal crops: reproductive development and grain filling.

Increasingly frequent extreme heat events threaten cereal production and food security under a changing climate. The reproductive-to-grain formation continuum of cereals is particularly vulnerable to elevated temperatures, as heat stress disrupts developmental processes from inflorescence formation and fertilization to grain filling and quality establishment. These disruptions reduce reproductive success, impair yield formation, and compromise grain quality. A comprehensive understanding of the developmental, physiological, molecular, and genetic basis of cereal heat tolerance is therefore essential for developing climate-adapted crops. This review summarizes recent advances in understanding heat stress during cereal reproduction and grain filling across major cereal crops. We first discuss how heat stress affects sequential developmental processes, including inflorescence development, gametophyte development, flowering and pollination, fertilization, and grain filling. We then integrate emerging evidence on cross-cutting mechanisms that connect stage-specific heat responses, focusing on hormonal and redox homeostasis, carbohydrate metabolism and source-sink coordination, proteostasis and endomembrane organization, and genome stability and multilayered gene regulation. Finally, we summarize the genetic basis of cereal heat tolerance by highlighting genetic determinants, favorable alleles, and their potential applications in breeding. We further discuss current bottlenecks and future opportunities for breeding heat-tolerant cereals.

Cereals

Inulin, Containing Frutco-Oligosaccharides, and Generalized Anxiety Disorder 7-Item Scale Scores in College Students.

This study was conducted to determine the effects of fructo-oligosaccharide (FOS) inulin on anxiety symptoms in college students. Forty million adults in the United States suffer from anxiety. Previous studies have viewed gut microbiota and its potential link to anxiety in both humans and mice. However, no previous studies focused on the effect of FOS inulin on college students. Fourteen subjects received 4.9 g per day of FOS inulin as the treatment (TX) or no supplement as the control (CON) for 28 days. Both the TX and CON groups were given the Generalized Anxiety Disorder 7-Item Scale (GAD-7) on days 1 and 28. Both groups were also given a 3-day food log at the beginning of the experiment and otherwise maintained their regular diet. Results showed a statistically significant decrease in median GAD-7 scores in both groups (P = .017, r = .637 and P = .042, r = .587 for the TX and CON groups, respectively). However, when comparing the GAD-7 scores between groups, no statistically significant results were found. FOS inulin supplementation did not alleviate anxiety symptoms in college students participating in this study.

Adolescent

Structural and physicochemical characterisation of branched dextrans produced by an active &#x3b1;-(1&#x2192;2) branching sucrase from Apilactobacillus kunkeei PDER37.

Recently, branching sucrases encoded in the genomes of certain Lactic Acid Bacteria (LAB) strains have become novel enzymes to obtain branched &#x3b1;-glucans. In this study an active &#x3b1;-(1&#xa0;&#x2192;&#xa0;2) branching sucrase from Apilactobacillus kunkeei PDER37 was expressed, characterised and distinct branched dextrans was obtained with reactions under different sucrose: dextran ratio. Structural characterisation by 1H and 13C NMR analysis demonstrated the branching of the dextran with (1&#xa0;&#x2192;&#xa0;2)-linked &#x3b1;-d-glucose units with no alteration in the final structure depending on sucrose: dextran ratio (D0) but this ratio was effective for the determination of the molecular weights of the branched dextrans (D1, D2 and D3). FTIR analysis further supported the dextran structures and suggested the higher accumulation of the &#x3b1;-Glc units in the branched dextrans. Thermal characterisation of the branched dextrans obtained by TGA and DSC analysis suggested the increased hygroscopicity of the branching units. Both SEM and AFM analysis demonstrated more porous chain like structures in the branched dextrans. This study provides valuable information on the role of active &#x3b1;-(1&#xa0;&#x2192;&#xa0;2) branching sucrase (BS37) for the production of branched dextrans with potential increased physicochemical status applicable for food and other industries.

Dextrans

Differences in circadian rhythm changes between myopic and non-myopic college students over 2&#x2009;years.

This study aimed to characterize and compare the differences in circadian rhythm changes during 2&#x2009;years between college students with myopia and non-myopia based on a longitudinal cohort study. Wake-up time and bedtime were obtained through a self-administered questionnaire. Chronotype was assessed using the reduced Morningness-Eveningness Questionnaire (rMEQ). Circadian rhythm timing was determined by dim-light melatonin onset (DLMO), measured through hourly saliva collection from 21:00 to 01:00. A total of 450 college students (146 [32.4%] males) with a mean age of 18.65&#x2009;&#xb1;&#x2009;1.05&#x2009;years were included, of whom 353 (78.4%) students had myopia. Compared with non-myopic individuals, myopic students slept later, woke up earlier, and exhibited lower rMEQ scores at baseline. Over the 2-year follow-up, both groups showed significantly earlier bedtimes, later wake-up times, and higher rMEQ scores. Only myopic students demonstrated a 45-minute delay in DLMO after the 2-year follow-up. After adjusting for potential confounders, linear mixed-effects models showed that myopic individuals had later bedtimes and earlier wake-up times. These findings indicate significant circadian rhythm changes in individuals with myopia, suggesting the potential of targeted sleep rhythm interventions on preventing myopia.

Myopia

Impaired adaptation to smoke-derived phenolic compounds in Listeria monocytogenes CC204 from smoked salmon and trout.

Listeria monocytogenes is a major foodborne pathogen in ready-to-eat smoked fish products. This study evaluated whether clonal complex affiliation contributes to variability in growth responses to stresses representative of smoked salmon and trout processing. Ten strains were studied, including strains from CC121, CC26 and CC204, the three major clonal complexes reported in the French smoked salmon and trout sectors, together with the EGDe reference strain. Strains were exposed to salt, cold, smoke-derived phenolic compounds and combined stress conditions. Growth responses were compared with whole-genome-based phylogeny, and the impaired phenotype observed under phenolic exposure was further investigated using viable counts, live/dead microscopy and comparative genomics. Growth profiles were partly structured by clonal complex, with strains from the same clonal complex showing similar behaviour across stress conditions. Salt and cold reduced growth globally, while smoke-derived phenolic compounds were the most discriminating conditions. CC204 strains showed markedly lower growth rates under phenolic exposure than CC121, CC26 and EGDe. This phenotype was not associated with loss of cultivability or significant loss of membrane integrity. Comparative genomics did not identify a clear gene-content determinant explaining the CC204 phenotype. These results suggest that CC204 has an impaired adaptive response to smoke-derived compounds, likely involving regulatory or physiological mechanisms.

Listeria monocytogenes

Mining Stored-Specimen Studies for Information about Cancer Natural History.

The advent of new multicancer early detection tests and publication of early diagnostic results have generated expectations of clinical benefit from multicancer screening. The clinical benefit of a cancer screening test depends critically on disease natural history, which is typically learned from prospective screening studies. Retrospective studies of stored blood specimens are important in learning about a test's preclinical diagnostic performance but have rarely been used to infer natural history. The extent to which these studies might be harnessed to also learn natural history is discussed in the context of an article in this issue that infers the combined natural history of a range of cancers targeted by a multicancer early detection test using a case-control subsample of specimens from a large cohort study. The critical question concerns the identifiability of key transition rates in multistate models of natural history alongside state-specific sensitivities. The article suggests that these parameters are estimable within a Bayesian framework that leverages prior information about test sensitivity from diagnostic studies. We offer a heuristic discussion of identifiability in this setting and encourage formal study to determine the extent to which models with varying degrees of complexity may be learned from stored-specimen studies. See related article by Dai et al., p. 1535.

Humans

Genetic diversity and recombination of&#xa0;NA-PRRSV field strains in Vietnam: Implications for vaccine efficacy.

Porcine reproductive and respiratory syndrome (PRRS) causes severe reproductive losses in pregnant sows and piglets, resulting in substantial economic impact on the swine industry worldwide. However, due to the significant genetic diversity and rapid evolutionary changes of the pathogen, continuous surveillance and detailed genetic analysis of circulating strains are essential. The current study aimed to evaluate the genetic diversity of the hypervariable (HV) region of non-structural protein 2 (nsp2) among North American PRRSV strains isolated from swine farms in Vietnam. Phylogenetic analysis and multiple sequence alignment were conducted to determine subtype classification and assess genetic variability. A total of 48 field isolates were obtained, of which 12.5% belonged to classical NA-PRRSV, 16.6% to NADC30-like and 70.9% to HP-PRRSV, primarily distributed across sublineages 1.4, 5.1, 8.7 and 8.9. Amino acid comparisons found multiple insertions, deletions and substitutions at various positions within the hypervariable region of nsp2. The study revealed substantial genetic variation in the HV region of nsp2 among NA-PRRSV field strains, largely associated with recombination and immune escape. These findings highlight epidemiological risks to vaccine efficacy and underscore the need for continuous molecular surveillance to support effective PRRSV control in Vietnam.

PRRSV

How to assess different types of abstract concepts in brain disorders: A systematic review.

The clinical evaluation of semantic knowledge has predominantly relied on tools targeting concrete concepts, whereas abstract knowledge has historically received limited attention despite its importance in everyday communication. Only a few instruments have explored the internal subdivision of abstract knowledge, likely due to the intrinsic difficulty of defining specific types of concepts or dimensions, resulting in a fragmented and heterogeneous neuropsychological assessment framework that limits our understanding of this domain. This systematic review examined the tools used to assess various types of abstract concepts in clinical populations. A literature search has been performed on the electronic databases of PubMed and Google Scholar (last update: October 2025). A total of 17 tests is reviewed, differing in the test characteristics, i.e. ranging from automatic to controlled processes and varying in ecological validity, the type of stimuli employed, and the abstract dimensions explored. Most studies have focused on neurodegenerative patients, while comparatively few have examined other clinical conditions. The risk of bias of the reviewed studies was assessed using an ad hoc developed instrument. This review highlights the need for future research to extend investigations to additional abstract domains and clinical populations, while also identifying key challenges related to stimulus selection and the determination of the most appropriate assessment framework.

Humans