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Utility of short-term tests for genetic toxicity.

By definition, short-term tests (STTs) for genetic toxicity detect genotoxic agents, not carcinogens specifically. However, there is sufficient evidence, based on mechanistic considerations alone, to say that genotoxic agents are potential carcinogens. STTs have high statistical power, are almost always replicated, can be performed rather easily under various sets of experimental conditions, are relatively inexpensive, and detect a variety of endpoints relevant to carcinogenesis. In addition, several STTs have shown considerable utility in evaluating the genotoxic effects of real-world, environmental complex mixtures as well as the antimutagenic effects of various pure compounds and complex mixtures. STTs are likely to continue to be refined, resulting in STTs that are increasingly more relevant to human mutation and disease. Their utility should not be judged solely against the questionable standard of a rodent carcinogenicity assay.

Animals↗

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‑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‑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↗

Discrimination of random, time-varying spectra with statistical constraints.

In the present study, a sample-discrimination procedure is used to examine how various statistical constraints on random, time-varying spectra might aid listeners in discriminating among these signals. Time-varying spectra were constructed by adding five sequences of tones, five tones in each sequence, centered at the octave frequencies from 250 to 4000 Hz. The levels, frequencies, and durations of the tones varied randomly from one presentation to the next. The signal to be detected was an increment in the level of tones comprising the sequence centered at 1000 Hz (the target sequence). Three main conditions were examined in which the parameter values of tones varied independently of one another (equal-variance condition), covaried across tone sequences (cross-channel covariance condition), or covaried among themselves for each tone (cross-parameter covariance condition). For the latter two conditions, two special cases were examined in which the target sequence varied independently of nontarget sequences or varied according to the same statistical rules. For five of six listeners, comparisons of performance to that of an ideal, within-channel observer gave clear evidence of an ability to take advantage of cross-channel statistical constraints, but only when the target sequence varied independently of its context. Results offer no evidence for listeners' ability to take advantage of cross-parameter constraints. Trial-by-trial analyses in the equal-variance condition identify factors other than the appropriate weighting of information as primarily responsible for suboptimal performance, though individual differences complicate this interpretation. A failure of simple detection-theoretic models to account for these results is discussed in terms of possible perceptual rules governing sound source identification of real-world objects.

Adult↗

Orientation dependence of human line-length judgements matches statistical structure in real-world scenes.

A set of 42 photographs of real-world scenes were filtered by convolution with a Laphacian-of-Gaussian kernel. The linear density of zero-crossings along notional lines in the filtered images was measured as a function of the orientation of those lines. The zero-crossing density was found to be greatest along near-vertical lines and least along horizontal lines. The peaks in this function were much broader than the troughs, and there was weak evidence of a small decline in density along lines at and very close to vertical. Psychophysical measurements of the apparent length of a line as a function of its orientation (by the current author and others) show very similar variation, subject to an overall scaling factor. This close correspondence is taken as strong evidence for some sort of environmental determination of the orientation dependence of human length judgements.

Humans↗

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 (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × 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 2×2 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 (I²=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 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® 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 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 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 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↗

Reporting presence or absence of named objects by a language-trained dolphin.

Referential "reporting" was defined as the transmission of information about the presence or absence of symbolically-referenced real-world objects. In Experiment 1 two bottlenosed dolphins (Tursiops truncatus), trained in earlier studies to carry out instructions conveyed by imperative sentences expressed in artificial gestural or acoustic languages, each gave spontaneous indications that an object referenced in an imperative was absent from their tank. In Experiment 2 the dolphin tutored in the gestural language was taught to make explicit reports of object absence by pressing a "No" paddle in response to imperatives referencing an absent object. Absence was reported correctly on 84% of 97 missing-object probes inserted at random intervals among 598 sentences referring to objects that were present. Reports were typically made after active search of the tank for an average of 15.0 sec. False reports, that objects present were absent, were few (7.5%). In Experiment 3, the dolphin was taught an interrogative sentence form that enabled us to ask direct questions about the presence or absence of specific objects. Responses by the dolphin on the No paddle indicated absence, while responses on a "Yes" paddle indicated presence. From one to three objects were shown the dolphin and then placed in the tank in a discrete-trial procedure. In response to the interrogative, reports or object presence or absence were better than 91% correct with a single object in the tank and either that object or some other object referenced; accuracy declined to 72-78% correct with three objects present, but was still well above chance. Several lines of evidence suggested that the dolphin was attempting to remember which objects it had been shown, rather than conducting an active environmental search as in Experiment 2. The memory strategy became less efficient as the number of objects to be remembered increased. Overall, the results evidenced the language-trained dolphin's understanding of references to present or absent objects, its ability to inventory its environment to seek information about those objects, and its ability to report its obtained knowledge to others.

Animal Communication↗

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↗

Sparseness of the neuronal representation of stimuli in the primate temporal visual cortex.

1. To analyze the selectivity and the sparseness of firing to visual stimuli of single neurons in the primate temporal cortical visual area, neuronal responses were measured to a set of 68 visual stimuli in macaques performing a visual fixation task. The population of neurons analyzed had responses that occurred primarily to faces. The stimuli included 23 faces, and 45 nonface images of real-world scenes, so that the function of this brain region could be analyzed when it was processing natural scenes. 2. The neurons were selected to meet the previously used criteria of face selectivity by responding more than twice as much to the optimal face as to the optimal nonface stimulus in the set. Application of information theoretic analyses to the responses of these neurons confirmed that their responses contained much more information about which of 20 face stimuli had been seen (on average 0.4 bits) than about which (of 20) nonface stimuli had been seen (on average 0.07 bits). 3. The sparseness of the representation of a scene or object provided by each of these neurons (which can be thought of as the proportion of stimuli to which the neuron responds, and which is fundamental to understanding the network operation of the system) can be defined as [formula: see text] where ri is the firing rate to the ith stimulus in the set of n stimuli. The sparseness has a maximal value of 1.0. It was found that the sparseness of the representation of the 68 stimuli by each neuron had an average across all neurons of 0.65. This indicates a rather distributed representation. 4. If the spontaneous firing rate was subtracted from the firing rate of the neuron to each stimulus, so that the changes of firing rate, i.e., the responses of the neurons, were used in the sparseness calculation, then the "response sparseness" had a lower value, with a mean of 0.33 for the population of neurons, or 0.60 if calculated over the set of faces. 5. Multidimensional scaling to produce a stimulus space represented by this population of neurons showed that the different faces were well separated in the space created, whereas the different nonface stimuli were grouped together in the space. 6. The information analyses and multidimensional scaling provided evidence that what was made explicit in the responses of these neurons was information about which face had been seen.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The interpretation of visual motion: evidence for surface segmentation mechanisms.

The independent motions of objects in a visual scene are commonly manifest as overlapping retinal motions. A consequence of this overlap is the creation of spurious retinal image features--such as corners and terminated contours--that bear no direct relation to the motions of the objects that give rise to them. To reconstruct object motions, these emergent features must be distinguished from the retinal motions of real object features. This process can be studied using visual stimuli known as plaid patterns, which provide a laboratory archetype for the ubiquitous real-world circumstance of two surfaces with overlapping retinal projections. By adjusting luminance relationships in a plaid pattern it is possible to influence the perceptual interpretation of image features, such that they are seen as either an emergent consequence of occlusion or as real variations in surface reflectance. In the former case, the plaid is most likely to be to perceived as two independently moving surfaces, whereas the latter generally elicits a percept of a single moving surface. This dependence of motion perception on luminance configuration can be viewed as evidence for the involvement of surface segmentation mechanisms, which distinguish between real and emergent image features by promoting a depth-ordered neural representation of surfaces. An alternative interpretation, which does not demand such depth-ordering and feature classification, asserts that the effect of luminance configuration can be accounted for by attendant variations in the distribution of moving Fourier components. To evaluate these two proposed mechanisms, we designed novel plaid stimuli in which surface segmentation cues could be varied independently of changes in the distribution of Fourier components. Perceived motion was found to be highly correlated with the presence of appropriate segmentation cues and uncorrelated with the distribution of Fourier components. These results refute the Fourier components hypothesis, and they support our proposal that surface segmentation plays a critical role in the interpretation of visual motion signals.

Contrast Sensitivity↗