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A systematic review of human avoidance learning: Cognition, computation, and methods.

Avoidance behaviour is fundamental for survival but can become maladaptive in clinical conditions. A large body of literature has accumulated on the dynamics of human avoidance learning. However, current theories and overviews do not provide an exhaustive account of this evidence. In this systematic review, we identify N = 116 studies on human avoidance learning. We analyse these studies with the goal of distilling robust empirical phenomena as a basis for theory-building, and examine their diagnostic value in differentiating between competing theories. We find that the evidence is difficult to reconcile with foundational two-factor and classical safety-signal accounts, and most strongly supports expectancy- and inference-based views, in which avoidance responses are selected with respect to represented consequences. At the same time, no current framework provides a complete account of the evidence: several findings point to an additional role for operant valuation, Pavlovian influences, and contextual or latent-state control over the expression of avoidance. Methodologically, we observe that the problem setting in the most common experimental paradigms is radically simpler than real-world avoidance and therefore unlikely to expose the limits of inferential or reflective mechanisms. Consequently, we argue that paradigms with greater computational demands and more realistic action affordances are required to identify the mechanisms underlying avoidance learning. Collectively, these insights provide a foundation for theoretical refinement, computational modelling, and methodological innovation, with implications for advancing interventions targeting maladaptive avoidance.

Humans↗

Efficacy of prescription-eligible digital health applications for depression and generalized anxiety disorder in Germany: a systematic review and meta-analysis.

In Germany, prescription-eligible digital mental health applications (DiGA) were introduced in 2020 as promising interventions to address, among others, depression and anxiety disorders, two of the most prevalent mental health conditions worldwide. Despite growing interest in DiGAs, their overall efficacy remains uncertain. This study aimed to systematically evaluate and quantify the efficacy of prescription-eligible digital interventions for depression and generalized anxiety disorder by synthesizing evidence from randomized controlled trials (19 trials; total N = 4,078; pooled mean age = 38.7 years, SD = 12.1). Here we show that prescription-eligible digital applications for depression and generalized anxiety disorder reduce symptom severity compared with control conditions. For depression, effects were observed both immediately after the intervention (number of apps = 5; k = 17; SMD = - 0.49; 95% CI - 0.65 to - 0.32) and at follow-up (number of apps = 1; k = 4; SMD = - 0.35; 95% CI - 0.46 to - 0.29), while evidence for generalized anxiety disorder was limited due to a small number of available studies (number of studies = 2). These findings support the integration of evidence-based digital tools into mental health treatment strategies in Germany. However, the available evidence is currently dominated by a small number of applications, particularly Deprexis, and should therefore not be interpreted as equally representative of all DiGAs currently listed for depression in Germany. The findings also highlight methodological limitations of current research and underscore the need for real-world evaluations, which address not only efficacy but also the effectiveness, content, quality and implementation.

Generalized Anxiety Disorder↗

Exploring the emerging concept of precision rehabilitation: a qualitative study.

PURPOSE: This descriptive qualitative study explored knowledge users' perspectives on precision rehabilitation concepts, barriers, facilitators, and future directions as part of a convergent mixed methods scoping review. MATERIALS AND METHODS: Sixteen clinicians, administrators, and researchers from three North American tertiary care rehabilitation centers were recruited using convenience and snowball sampling to participate in individual semi-structured interviews. Conventional qualitative content analysis followed a deductive thematic approach based on predetermined categories. RESULTS: Analyses revealed three main themes: (1) Although precision rehabilitation shares foundational concepts with precision medicine, there are certain elements, such as personalization, that are uniquely expressed; (2) Rehabilitation-specific facilitators to precision approaches include the use of unobtrusive technology to collect large amounts of data in real-world contexts, while barriers include rehabilitation's typically small, heterogeneous sample sizes; and (3) The future of precision rehabilitation will require collaborative data-sharing to focus on determining care trajectories that enhance functional outcomes. CONCLUSION: Findings provide the first qualitative synthesis of knowledge users perspectives to complement quantitative evidence and inform the emerging field of precision rehabilitation.

Humans↗

The role of pathology laboratories in integrating genetic testing into Australian primary care: an implementation science perspective.

As genomic testing moves into mainstream healthcare, non-genetic healthcare professionals, including general practitioners (GPs), play a critical role as gatekeepers to genetic services. Laboratories are essential in supporting this transition by providing not only high-quality genetic tests but also point-of-care tools, educational materials and clinical guidance to support their use. This study aimed to explore how these tools and supports are conceptualized, developed, implemented and evaluated and how laboratories integrate them into their relationships with GPs, an essential process for paving the way toward better use of genomics in primary care. A qualitative study design was employed using semi-structured, in-depth interviews with representatives from genetic laboratories across Australia. The Consolidated Framework for Implementation Research (CFIR) guided deductive content analysis of data. Findings spanned the four CFIR domains (Intervention Characteristics, Outer Setting, Inner Setting and Implementation Process) across 34 constructs. Participants reported that laboratories viewed point-of-care tools and resources as essential responses to persistent genomic knowledge gaps among GPs. Development of evidence-based, practice-driven and adaptable resources was supported and rewarded within laboratory organisations. A strong culture of clinical responsibility and implementation readiness, combined with robust networks and communications, enabled timely support for GPs. Gaps identified included lack of implementation planning, misalignments between laboratory-developed resources and GPs' real-world needs and inadequate mechanisms for obtaining GPs' feedback, which made evaluation problematic. By applying an implementation science framework, these findings provide insights for future efforts to build and sustain the provision of point-of-care tools and support, ultimately improving the integration of genomics in primary care.

Journal Article↗

Polygenic risk score for early identification of coronary artery disease in a real-world clinical setting within the Latvian patient population.

STUDY OBJECTIVE: Polygenic risk scores (PRS) are increasingly recognized for their potential to improve coronary artery disease (CAD) prediction beyond traditional clinical models. This study evaluated the utility of genome-wide association study (GWAS) - derived PRS and pathway-specific PRS (PS-PRS) in the Latvian population, aiming to assess their association with CAD and compare their predictive performance with conventional risk factors. DESIGN PARTICIPANTS AND MAIN OUTCOME MEASURES: The study included 90 early-onset CAD patients and 43 controls with no evidence of atherosclerotic lesions on coronary angiography, with next-generation sequencing performed. PRS was calculated using 192 single nucleotide variants identified from the CARDIoGRAMplusC4D GWAS meta-analysis. The predictive accuracy of PRS, PS-PRS, clinical risk factors, and their combinations was analyzed via ROC curves. RESULTS: The average age was 48.7&#xa0;years in CAD patients and 49.8 in controls. CAD patients showed significantly higher PRS (mean 0.31) compared to controls (mean&#xa0;-&#xa0;0.65; p&#xa0;<&#xa0;0.0001). PRS alone had moderate discriminatory power (AUC&#xa0;=&#xa0;0.773), slightly lower than LDL cholesterol (AUC&#xa0;=&#xa0;0.775) and total cholesterol (AUC&#xa0;=&#xa0;0.821). Combining clinical risk factors improved prediction (AUC&#xa0;=&#xa0;0.872), with the highest accuracy when PRS was integrated with all clinical factors (AUC&#xa0;=&#xa0;0.933). The PRS distributions were significantly elevated in early-onset CAD patients across the angiogenesis/tissue repair pathway (p&#xa0;=&#xa0;0.00038), inflammation pathway (p&#xa0;=&#xa0;0.043), vascular remodelling pathway (p&#xa0;=&#xa0;0.0116), and pathway of genes with unknown function in atherosclerosis (p&#xa0;=&#xa0;0.0035), but overall PRS demonstrated superior discrimination compared to pathway-specific PRS. CONCLUSIONS: Incorporating PRS enhances early-onset CAD risk prediction. Pathway specific PRS had lower discriminative ability than the overall PRS.

Atherosclerosis↗

Aquablation/AquaBeam Waterjet Therapy for Benign Prostatic Hyperplasia: Three-Year Functional and Ejaculatory Outcomes in a Multicenter Real-World Italian Cohort.

OBJECTIVE: To evaluate the 3-year functional outcomes of Aquablation/AquaBeam waterjet therapy for bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), with particular attention to urinary symptoms, quality of life, continence, ejaculatory function, and complications. METHODS: We performed a retrospective analysis of a prospectively maintained multicenter database including 218 consecutive men who underwent Aquablation/AquaBeam for symptomatic BPH between January 2019 and January 2022 at three referral centers. Functional outcomes assessed preoperatively and during follow-up included International Prostate Symptom Score (IPSS), IPSS quality-of-life item (IPSS-QoL), maximum urinary flow rate (Qmax), post-void residual urine (PVR), continence, and ejaculatory function. Median follow-up was 36&#x2009;months. Ejaculatory preservation was evaluated only in patients with preserved antegrade ejaculation at baseline. RESULTS: Median age was 61&#x2009;years (IQR 57-66), median prostate-specific antigen (PSA) was 2.52&#x2009;ng/mL (IQR 0.40-21.60), and median prostate volume was 55&#x2009;mL (IQR 40-73). Median operative time was 56&#x2009;min, while median catheterization time and length of hospital stay were both 48&#x2009;h. Functional improvements were evident from the 3-month follow-up and remained stable through 36&#x2009;months. At 36&#x2009;months, median IPSS improved to 5 and median Qmax to 18&#x2009;mL/s. Median PSA changed modestly from 2.52&#x2009;ng/mL at baseline to 2.75&#x2009;ng/mL at 36&#x2009;months. No cases of de novo urinary incontinence were observed throughout follow-up. Among patients with preserved antegrade ejaculation at baseline, 87% maintained antegrade ejaculation at 36&#x2009;months. Most postoperative complications were minor (Clavien-Dindo grade I-II, 20.2%). One grade III rectal injury occurred (0.5%). Median hemoglobin decreased from 15.2&#x2009;g/dL preoperatively to 14.0&#x2009;g/dL before hospital discharge, and two patients required blood transfusion. During the 36-month follow-up, no surgical retreatment was required, whereas 11 patients (5.0%) received temporary medical retreatment. CONCLUSION: In this multicenter real-world cohort, Aquablation/AquaBeam was safe and effective over 3&#x2009;years, providing durable improvement in lower urinary tract symptoms and quality of life while preserving continence and antegrade ejaculation in most patients. These findings support Aquablation/AquaBeam as a valuable minimally invasive surgical option for selected men with BPH, particularly those who prioritize preservation of ejaculatory function. Longer-term and comparative studies are warranted. TRIAL REGISTRATION: 48281.

Humans↗

Beyond data and technology: the need for new thinking to enable the era of precision prevention.

BACKGROUND: Global flagship initiatives increasingly advocate for proactive health maintenance to alleviate the growing burden on reactive, disease-focused healthcare systems. Precision prevention is conceived as the targeted modulation of causal pathways across the disease continuum, from latent risk and pre-disease states to clinical manifestation, surpassing conventional public health prevention strategies that prioritise managing population-level risk factors. Traditional discovery and implementation models, however, remain poorly aligned with the pace and breadth of scientific and technological advances. This review outlines key barriers to scaling precision prevention and argues for the integration of conceptual, methodological, and policy perspectives into a single implementation&#x2011;oriented framework. MAIN: Individualised risk stratification lies at the core of precision prevention. Genomics serves as a stable substrate for lifetime susceptibility assessment, while meaningful prediction in multifactorial chronic disease requires additional risk monitoring using dynamic intermediate molecular markers and high-resolution exposomic data. Machine learning and other artificial intelligence (AI) methods are increasingly helpful tools for integrating large, heterogeneous and temporally structured real-world data to generate personalised predictions of health trajectories. Trustworthy AI-enabled risk prediction or decision-support systems are expected to provide transparency about model logic, assumptions and performance. In discovery, existing diagnostic classifications and conventional case-control designs can obscure mechanistic heterogeneity. Shifting toward precision phenotyping and biologically grounded disease redefinition could reveal a new layer of molecular understanding. Evidence generation strategies that reflect the temporal change of disease, including high&#x2011;risk enrichment, surrogate endpoints, and adaptive, trajectory-based monitoring, are particularly important for common conditions with prolonged latency periods (e.g., cancer, cardiovascular disease). Features often dismissed as "noise", such as stochastic molecular variation and minimal exposures, may in fact encode meaningful individual-level signals and thus merit investigation. CONCLUSION: To shift healthcare from reactive treatment toward proactive health maintenance requires coordinated action from stakeholders to reshape the pillars of discovery, reform outcome assessments and modernise implementation strategies.

Humans↗

GAMMA: gap-aware motif mining under incomplete labeling with applications to MHC motifs.

MOTIVATION: Sequence motif identification is crucial for understanding molecular recognition, particularly in immune responses involving peptide binding to major histocompatibility complex (MHC) Class I molecules for antigen presentation to T cells. Traditionally, MHC Class I binding motifs are assumed to be contiguous and span nine amino acids. However, structural evidence suggests that binding may involve nonadjacent residues, challenging the assumptions of existing methods. RESULTS: In this study, we propose Gap-Aware Motif Mining Algorithm (GAMMA), a probabilistic framework designed to identify noncontiguous motifs under conditions of incomplete labeling. GAMMA employs Bayesian inference with Markov chain Monte Carlo sampling to jointly estimate motif parameters, binding locations, and the relative spacing between binding positions. Through extensive simulations and real-world applications to MHC Class I peptide datasets, GAMMA outperforms existing motif discovery tools such as GLAM2 in accurately localizing binding residues and identifying the underlying motifs. Notably, our results suggest that the true number of binding residues may be eight, fewer than the commonly assumed nine. In addition, for longer peptides, the model captures increased flexibility in the central region, consistent with structural observations that peptides may bulge in the middle. AVAILABILITY AND IMPLEMENTATION: The raw data and the source codes are available on GitHub (https://github.com/RanLIUaca/GAMMAmotif).

Amino Acid Motifs↗

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (&#x3b2;&#xa0;=&#xa0;-0.45; 95%CI[-0.70, -0.19]; FDR-p&#xa0;=&#xa0;0.003) and verbal memory (&#x3b2;&#xa0;=&#xa0;-0.45; 95%CI[-0.72, -0.18]; FDR-p&#xa0;=&#xa0;0.003). Significant time &#xd7; group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗

Diagnostic Performance of Machine Learning for Systemic Lupus Erythematosus: Systematic Review and Meta-Analysis.

BACKGROUND: Early and accurate diagnosis of systemic lupus erythematosus (SLE) and its organ involvement is essential. Previous reviews of machine learning (ML) in SLE combined heterogeneous tasks and validation strategies and may have overinterpreted model performance. OBJECTIVE: This study evaluated the diagnostic performance of ML and deep learning (DL) models for 3 clinically distinct SLE-related tasks: SLE classification or diagnosis, lupus nephritis (LN) diagnosis, and neuropsychiatric systemic lupus erythematosus (NPSLE) discrimination. We also assessed methodological quality and certainty of evidence. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and IEEE Xplore were searched from January 2014 to April 2026. Eligible peer-reviewed diagnostic accuracy studies developed or validated ML or DL models for 1 of the 3 prespecified tasks, used an accepted reference standard, and provided data for a 2&#xd7;2 contingency table. Bivariate random-effects meta-analyses with the Hartung-Knapp-Sidik-Jonkman adjustment were used to pool sensitivity and specificity. We reported 95% prediction intervals (PIs), assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies for Artificial Intelligence tool (QUADAS-AI; Viknesh Sounderajah [Imperial College London]), and evaluated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework for diagnostic test accuracy. RESULTS: Twenty-nine studies were included: 17 for SLE classification, 5 for LN diagnosis, and 7 for NPSLE discrimination. In the primary task-stratified analysis, pooled sensitivity was 0.91 (95% CI 0.86-0.94; 95% PI 0.56-0.99), and pooled specificity was 0.94 (95% CI 0.91-0.96; 95% PI 0.69-0.99), with low heterogeneity (I&#xb2;=23.9% and 22.9%, respectively). DL models showed a sensitivity of 0.93 and specificity of 0.95, compared with 0.88 and 0.94 for traditional ML models. Certainty of evidence was high for most analyses but low for LN diagnosis because of inconsistency and imprecision. All studies were retrospective, and only 9 of 29 (31%) performed independent external validation. Overall risk of bias was high or unclear in 22 of 29 (75.9%) studies. No study reported model calibration, decision-curve analysis, or net clinical benefit. CONCLUSIONS: ML models showed promising diagnostic accuracy across 3 distinct SLE-related tasks, but wide PIs, limited external validation, and pervasive risk of bias restrict conclusions about real-world generalizability. Prospective multicenter studies with standardized tasks and reference standards, independent external validation, and formal assessment of calibration and clinical utility are required before clinical implementation.

Humans↗

Artificial Intelligence Technologies in Nursing Clinical Decision-Making: An Umbrella Review.

AIM: To describe contemporary peer-reviewed literature on artificial intelligence in nurses' clinical decision-making. METHODS: An umbrella review of literature reviews. DATA SOURCES: Four major databases were searched for reviews published between 2019 and 2024. RESULTS: Sixteen literature reviews reported on 965 nursing artificial intelligence primary studies. The studies focused on technology development and emerging performance evaluations, whilst real-world testing or implementation in nursing clinical settings was rare. Rigorous comparative analyses were lacking. While artificial intelligence demonstrates promise in decision-making, challenges such as a lack of controlled studies, algorithmic bias, limited reproducibility and insufficient clinical trials hinder its practical impact. Ethical concerns, transparency and patient data privacy issues pose barriers to AI integration in nursing practice. Ethical and legal guidelines for patient privacy are needed and should be taught along with AI literacy training for nurses. CONCLUSIONS: Artificial intelligence has the potential to enhance clinical nursing decision-making, although evidence is limited by too few examples of nurse participation during development. Underutilisation in administrative nursing functions hinders implementation. Nurses should assume a central role in the design and development of AI applications to ensure that these technologies address the realities of nursing practice. With such improvements, artificial intelligence can transform nursing practice, improve nurses' clinical decision-making and ultimately enhance consumer healthcare outcomes. PATIENT OR PUBLIC INVOLVEMENT: No Patient or Public Involvement. REPORTING METHOD: While there is no reporting checklist for umbrella reviews, the PRISMA guide for systematic reviews was followed.

Artificial Intelligence↗

A commentary on measles vaccine in the context of outbreaks: Viral evolution, waning immunity and public trust.

The measles vaccine, introduced over 60&#x2009;y ago, has been proven to be both safe and effective. Despite the genetic diversity of the measles virus, eradication is considered possible with near-complete coverage of the two-dose vaccination schedule. However, real-world data show that this level of control has not yet been achieved. In addition to outbreaks among unvaccinated individuals, increasing numbers of measles cases are occurring among fully vaccinated, seropositive individuals. Both primary and secondary vaccine failures have been documented. Reduced vaccine effectiveness may occur in people with innate immune deficiencies, immunocompromised individuals (including those with HIV), and patients with chronic conditions such as diabetes. Furthermore, in regions without circulating wild-type virus, vaccine-induced antibody levels tend to decline over time and the impact of this may be more significant among infants. Emerging evidence highlights the importance of T lymphocyte - mediated immunity on effective B cell mediated immune response. Compounding the challenge, measles vaccination and infection are politicized, undermining public trust. Given the high transmissibility of measles, its potential for presymptomatic transmission, and the absence of specific early symptoms, complete eradication may not be feasible in the near term. Nevertheless, combining vaccine advocacy, transparent communication, and ongoing research will be critical to improving global vaccination strategies and public confidence.

Humans↗

Survey on the current status of novel cancer drug therapies for gynecological cancers in Japan: a nationwide survey by the Japan Society of Obstetrics and Gynecology (JSOG).

OBJECTIVE: To characterize real-world implementation of novel therapies in gynecological oncology in Japan and identify actionable gaps through a nationwide survey. METHODS: A cross-sectional questionnaire was distributed to Japan Society of Obstetrics and Gynecology-affiliated institutions. The items covered institution characteristics; use of poly (ADP-ribose) polymerase (PARP) inhibitors, immune checkpoint inhibitors (ICIs), kinase inhibitors, and antibody-based agents; local adverse event (AE) manuals; availability of expert panels and immune-related adverse event (irAE) teams; and perceptions of educational sufficiency. RESULTS: Valid responses were obtained from 245 institutions, spanning universities, cancer centers, and general hospitals. Most institutions reported the routine use of PARP inhibitors, ICIs, kinase inhibitors, and antibody drugs. However, only 40.4% of institutions had an in-hospital irAE management team, 57.1% had an AE/irAE manual, and 31.0% and 12.2% considered prior educational opportunities sufficient for physicians and nurses/other medical staff, respectively. High-volume institutions and academic centers were significantly more likely to have medical oncology support, expert-panel access, irAE teams, manuals, and higher self-rated evidence-based management capacity. The majority favored e-learning and society-led case conferences, and 76.3% supported the development of drug therapy subspecialties in gynecologic oncology. CONCLUSION: Innovative drug modalities are widely implemented across Japanese gynecological oncology services. However, critical gaps persist in multidisciplinary irAE management, standardized manuals, and practical education. Coordinated society-led programs to expand irAE teams, streamline companion diagnostics, disseminate ready-to-use algorithms, and provide credential-targeted training may enhance safety, equity, and evidence-concordant care nationwide.

Immune Checkpoint Inhibitors↗

Associations between smart infusion pump-electronic health record interoperability and healthcare outcomes: A systematic review.

OBJECTIVE: This study synthesized available evidence on the associations between smart infusion pump-electronic health record (EHR) interoperability and healthcare outcomes. METHODS: A systematic review of PubMed, CINAHL, Embase, and Scopus databases identified 901 records, which were imported into Rayyan&#xae; for duplicate removal, independent screening by three reviewers, and resolution of discrepancies. Eligible studies were peer-reviewed, data-driven, and reported associations between smart infusion pump-EHR interoperability and healthcare outcomes. Studies focused solely on technical validation or interoperability prototypes were excluded. A backward citation search identified additional studies. Two reviewers independently extracted and cross-validated study characteristics using standardized templates. Methodological quality was assessed with the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Twenty records of 14 full-text studies and 6 conference proceedings were included. Most records reported positive associations between smart infusion pump-EHR interoperability and outcomes related to safety (e.g., medication administration errors, safety-reported events, pump alerts, and compliance with interoperability and drug library), operational efficiency (e.g., programming and documentation time and technical issues), financial performance (e.g., charges captured, and cost avoided), and user experience domains. Most studies used observational designs, reflecting real-world interoperability implementations, where controlling confounding factors is challenging. Limited reporting of baseline characteristics, pump type, and sample sizes limited comparability across studies. CONCLUSIONS: Smart infusion pump-EHR interoperability was associated with improvements in patient safety, efficiency, charge capture, and user experience, with variable findings across studies. Future research should use rigorous methodologies and standardized measures, examine relationships across outcome domains, assess limitations of pump-EHR interoperability, and evaluate underexplored outcomes, including team communication, cognitive workload, and AI-enabled pumps. IMPLICATIONS FOR CLINICAL PRACTICE: Interoperability should be viewed as a component of a broader sociotechnical system, in which technology, user, workflow, clinical content, and organizational practices collectively determine overall effectiveness.

Humans↗

Personalised Nutraceutical Treatment Guided by MTHFR Genotype in Mental Health: A Retrospective Cohort Study.

BACKGROUND & AIMS: One-carbon metabolism plays a central role in neurotransmitter synthesis, methylation capacity, and neurobiological resilience. Variants in the methylenetetrahydrofolate reductase (MTHFR) gene can reduce enzymatic activity, affecting folate- and methionine-cycle functions and potentially influencing biological pathways relevant to mood and anxiety disorders. Personalised nutraceutical treatment strategies, particularly those addressing methylation capacity through targeted B-vitamin, folate, and adjunctive metabolic interventions are increasingly implemented in integrative clinical practice, yet evidence regarding their clinical outcomes remains limited. METHODS: We conducted a retrospective cohort study of 50 adults attending an integrative general practice clinic for anxiety and/or depression. All received personalised nutraceutical treatment informed by clinical assessment, laboratory testing and, for 37/50 patients, MTHFR genotyping. Psychological distress was measured using the Kessler-10 (K10) scale at baseline and approximately three months later. Secondary analyses evaluated whether outcomes differed by MTHFR genotype, whether specific supplements (e.g., L-methylfolate and SAMe) were associated with greater improvement, whether biomarker changes correlated with symptom change, and the safety/tolerability profile. RESULTS: Across the full cohort, mean K10 scores significantly decreased by four points over the treatment period, with 72% of patients showing clinical improvement. Reductions in psychological distress were seen across all MTHFR genotypes, including individuals with homozygous variant genotypes. Supplement-specific analyses showed improvement among those receiving methylfolate or SAMe, although the differences were not statistically significant. Following nutraceutical treatment, biomarker analyses demonstrated significant increases in serum vitamin B12 and modest reductions in homocysteine, but biomarker shifts did not correlate strongly with K10 change. No serious adverse events or clinically significant abnormalities in liver or renal function were identified. CONCLUSIONS: In this real-world primary care cohort, personalised nutraceutical treatment, grounded in one-carbon metabolism support and applied alongside usual care, was associated with clinically meaningful reductions in psychological distress. Outcomes were comparable across MTHFR genotypes when treatments were appropriately tailored, suggesting that genotype and biomarker-informed nutraceutical strategies may mitigate potential metabolic disadvantages. These findings support further controlled research into precision nutraceutical psychiatry for anxiety and depression. Secondary analyses of genotype subgroup, specific supplements, and biomarker-outcome associations are reported alongside Benjamini-Hochberg FDR-adjusted p-values and should be interpreted as hypothesis-generating.

Humans↗

Temporal shifts in gyrA mutation types and sublineage replacement in ST11 Salmonella enterica&#xa0;serovar Enteritidis over a decade (2014-2023): A genomic epidemiological study in Guangxi, China.

The overuse or abuse of antibiotics drives the global health threat of antimicrobial resistance. Although bans on certain veterinary antibiotics, such as colistin, have proven effective, the impact of fluoroquinolone stewardship on the evolution of the foodborne pathogen Salmonella enterica serovar Enteritidis (S. Enteritidis) remains unclear. Here, we conducted a decade-long (2014-2023) retrospective longitudinal genomic epidemiological analysis of 441&#xa0;ST11 S. Enteritidis isolates from Guangxi, China, alongside a global reference dataset of 4297 genomes. Our aim was to elucidate the effect of real-world antibiotic stewardship on the shift of gyrA point mutations and lineage distribution. Surveillance identified three global epidemic clade sublineages (GEC-L2, L3, L4), with the multidrug-resistant GEC-L4 (i.e., GC-c or MMC2), characterized by the gyrA mutation with amino acid substitution D87Y, being domestically dominant (70.07%, 309/441). Following China's 2016 ban on the veterinary use of critical fluoroquinolones, the proportion of the highly resistant GEC-L4 sublineage decreased continuously (from 86.84% in 2017 to 56.00% in 2023), while the less resistant GEC-L3 sublineage (i.e., GC-b or MMC1), mainly characterized by gyrA D87G, increased simultaneously (from 13.16% to 44.00%). This phenomenon might be attributed to the fact that the GEC-L4 sublineage exhibited a higher fitness cost compared with the GEC-L3 sublineage, as confirmed by the competition assay. A Random Forest Model validated that the gyrA mutation with amino acid substitution&#xa0;D87Y was the paramount feature for these sublineages' identification. In contrast, global data showed a continuous increase in gyrA mutations (from 8.63% in 2006 to 68.85% in 2024), primarily D87Y (from 1.44% to 31.15%) and D87N (from 4.32% to 22.95%), correlating with rising average fluoroquinolone consumption. This study provides direct genomic evidence that national-level antibiotic stewardship can drive the replacement of highly resistant sublineages with moderately resistant ones. These findings offer crucial scientific evidence for evaluating the impact of antibiotic management policies and inform strategies for the rational use of antimicrobials.

China↗

HER2DX genomic assay in HER2-positive early breast cancer treated with trastuzumab and pertuzumab: A correlative analysis from a real-world cohort.

BACKGROUND: HER2DX genomic assay is a genomic tool developed for personalizing care in early-stage HER2-positive breast cancer. This real-world analysis examines its associations with pathological complete response (pCR) and invasive disease-free survival (IDFS) following trastuzumab- and pertuzumab-based neoadjuvant therapy. MATERIALS AND METHODS: Retrospective, observational, single-center study of 156 patients with stage I-III HER2-positive breast cancer treated with dual HER2 blockade-based neoadjuvant therapy between February 2015 and May 2022&#x202f;at University Hospital A Coru&#xf1;a. HER2DX and clinicopathological variables were assessed in pretreatment tumor biopsies. Statistical analyses included Fisher's exact test, logistic regression, Cox proportional hazards models, and Kaplan-Meier estimates. RESULTS: HER2DX was performed in 111 tumors (71.2%). Overall pCR rate was 51.3%. Hormone receptor-positive disease was significantly associated with lower pCR (odds ratio [OR] 0.25, 95% CI 0.11-0.50; p&#xa0;<&#xa0;0.001), whereas HER2 immunohistochemistry 3+ showed a non-significant trend toward higher pCR (OR 2.95, 95% CI 0.96-11.08; p&#xa0;=&#xa0;0.075). Median IDFS was not reached, but hormone receptor-positive tumors showed better outcomes (hazard ratio [HR] 3.67, 95% CI 1.02-13.32; p&#xa0;=&#xa0;0.004 by log-rank). The association between HER2DX pCR score and pCR appeared heterogeneous. The continuous score was significantly associated with pCR in univariable analysis, not in multivariable model. In contrast, medium-high HER2DX pCR category showed significantly higher pCR rates than low category (OR 4.83, 95% CI 1.72-14.65; p&#xa0;=&#xa0;0.004). The continuous HER2DX risk score was independently associated with IDFS (HR 2.84, 95% CI 1.24-6.48; p&#xa0;=&#xa0;0.010). CONCLUSIONS: In this cohort, HER2DX scores were associated with pCR and IDFS, supporting previous evidence and highlighting potential role in treatment stratification.

Humans↗

A Smartphone-Based Ecological Momentary Intervention for Workplace Mental Health: Randomized Controlled Trial.

BACKGROUND: Work-related stress has been widely associated with an increased risk of various mental disorders and poor mental well-being. The fast-growing mobile health services industry has provided new opportunities for workplace mental health. OBJECTIVE: This randomized controlled trial examined the effectiveness of Neurum (Neurum Limited), a smartphone-based intervention tool featuring ecological momentary assessments and interventions that aims to reduce workplace stress in real-time and real-world settings. METHODS: A total of 201 working adults were recruited for a 4-week smartphone-based intervention that incorporated cognitive behavioral therapy, mindfulness exercises, and self-regulation exercises delivered on Neurum. A simple randomization procedure was used. Participants in the intervention group were encouraged to log mood journals, complete mental health exercises, and provide user feedback whenever applicable. The key outcome was measured by the Depression, Anxiety, and Stress Scale-21 items (DASS-21; Cronbach &#x3b1;=0.87). RESULTS: The intervention group consisted of 102 participants, while the control group consisted of 99 participants. More participants dropped out from the intervention group (n=21) than from the control group (n=2; &#x3c7;21=18.259; P<.001). The final sample consisted of 178 participants (male: 85/178, 47.8%; female: 93/178, 52.2%; mean age of 34.65, SD 7.67 y). Analyses revealed that after the 4-week intervention, the DASS-21 scores decreased in the intervention group (mean difference [MD]post-pre intervention=-14.518) but increased in the control group (MDpost-pre intervention=3.319; F1,176=59.358, P<.001; &#x3b7;2=0.252). This effect was largely led by stress reduction (F1,176=64.679, P<.001; for the intervention group, MDpost-pre intervention=-6.692, while for the control group, MDpost-pre intervention=2.000). On average, participants completed 6.27 (SD 9.4) exercises and provided 9.74 (SD 18.2) mood journal logs, with a daily engagement of 4.95 (SD 6.89) minutes. However, the associations between the changes in DASS-21 scores and the numbers of exercises or mood journal logs did not reach statistical significance. CONCLUSIONS: This study primarily established the effectiveness of Neurum in alleviating depression, anxiety, and stress symptoms in noninstitutionalized working adults, with a satisfactory user retention rate. Despite potential health-related culture differences, Neurum contributed to evidence-based digital health in nonclinical settings for timely needs and general accessibility as an alternative to traditional, face-to-face, and high-cost mental health services. Future directions involving a personalized approach in online mental health services were discussed.

Humans↗