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Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans

Alginate-based edible coating incorporating green tea extract for preserving postharvest quality and safety of white mushrooms (Agaricus bisporus).

This study aimed to evaluate the effects of a sodium alginate based edible coating incorporated with green tea extract (GTE) (Camellia sinensis) on the postharvest quality attributes and antimicrobial activity against Listeria monocytogenes in white mushrooms during refrigerated storage. The phenolic profile of GTE was characterized, and its minimum inhibitory concentration (MIC) against L. monocytogenes (1.6&#xa0;mg/mL) was determined. Sodium alginate coatings, with (ALG-GTE) or without GTE (ALG) at MIC (1.6&#xa0;mg/mL), were characterized (functional groups, solubility in water, moisture, thickness, water contact angle and color) for their chemical and physical properties. The effects of ALG-GTE coatings on quality parameters (firmness, weight loss, color, pH, sugars and organic acids), enzymatic activity [polyphenol oxidase (PPO), peroxidase (POD) and pectin methylesterase (PME)], antimicrobial activity against L. monocytogenes (5 log CFU/g), and surface characteristics (3D optical profilometry) were assessed in white mushrooms (Agaricus bisporus) during refrigerated storage (8&#xa0;days, 4&#xa0;&#xb1;&#xa0;1&#xa0;&#xb0;C, 90-95% RH). The ALG-GTE coatings preserved sugar composition, particularly rhamnose, reduced organic acids accumulation and delayed weight and firmness loss, reduced color changes, and decreased PME activity in coated white mushrooms. L. monocytogenes counts decreased by 1.4 log CFU/g after 1&#xa0;day, and no viable cells were detected after 2&#xa0;days (< 1.5 log CFU/g) in ALG-GTE coated white mushrooms. In addition, ALG-GTE coated white mushrooms exhibited smoother surfaces than uncoated samples. These findings highlight the potential of ALG-GTE coatings as a sustainable alternative capable of improving the microbiological safety and delaying the postharvest changes in fresh mushrooms.

Agaricus

A reanalysis of the Hitachi cohort study evaluating the effectiveness of low-dose CT screening for lung cancer.

The effectiveness of low-dose thoracic computed tomography (CT) screening for lung cancer for non-smokers or light smokers has been unclear. The results of the Hitachi cohort study performed by the conventional multivariable analysis suggested the reduction of lung cancer mortality by thoracic CT screening, but also revealed the lower all-cause mortality in the CT group, which indicated the existence of self-selection bias. Because the background of the subjects in the CT screening group and that in the X-ray screening group were very different, it is critical to adjust appropriately the confounding factors. In this brief report, we describe a re-evaluation of the results of the Hitachi Cohort Study performed by using more flexible methods, propensity score matching and inverse probability weighting.

epidemiology/public health

AI Health message intervention: The role of message customization and message source in breast cancer screening among women of color.

OBJECTIVES: To examine the effectiveness of breast cancer screening messages with varying levels of customization (generic, targeted, and tailored) and to compare AI-generated versus human-generated messages. METHODS: A between-subjects experimental design with a control condition was employed. Message content followed a standardized structure and varied by level of customization: generic, targeted (demographic-based), and tailored (perceived susceptibility- and barrier-based). Messages were developed by either the authors or GenAI (ChatGPT-4o). A total of 391 participants recruited via Prolific were randomly assigned to five groups (generic, targeted-human, targeted-AI, tailored-human, and tailored-AI). Self-efficacy, behavioral intentions, attitudes, and message believability were measured using different scales. RESULTS: Customized (tailoring and targeting) health messages performed comparably to generic messages in shaping positive health outcomes. GenAI-generated messages also produced outcomes comparable to those of human-generated messages under standardized conditions. Significant negative indirect effects through message believability for the human-tailored condition was found relative to the generic condition. CONCLUSIONS: GenAI may be a useful tool for developing and customizing scalable health messages. Its effectiveness depends not only on customization but also on maintaining message quality, including readability, clarity, coherence, naturalness, and credibility. PRACTICAL IMPLICATIONS: GenAI may support health practitioners in developing customized and scalable breast cancer messages. However, professional review remains necessary to ensure that the message is culturally appropriate, responsive to patient concerns, and suitable for use alongside patient-provider communication.

Humans

Effects of Digital Mental Health Screening Alone and With the Online MINDBODYSTRONG CBT-Based Program on Burnout, Depression, Anxiety, Healthy Behaviors, and Suicidal Ideation in at-Risk Nurses at 3- and 6-Months Post-Intervention: An&#xa0;RCT.

BACKGROUND: Burnout and mental distress among nurses are global public health epidemics that adversely affect nurse well-being and healthcare quality. Evidence-based, scalable mental health interventions are urgently needed. AIMS: To evaluate the 3- and 6-month outcomes of a randomized controlled trial (RCT) comparing a psychologically safe, digital mental health screening and referral program alone versus the same screening and referral program combined with the video-based online MINDBODYSTRONG&#xa0;(MBS) cognitive behavioral therapy (CBT)-based skills-building program among nurses at risk for mental distress. METHODS: 501 nurses were recruited from professional organizations and healthcare systems across the United States by email and randomized to either mental health screening and referral (standard care) or standard care plus the MBS cognitive behavioral skills-building intervention (the intervention). All study activities were conducted remotely. Follow-up surveys administered at 3- and 6-months assessed anxiety, depression, suicidal ideation, burnout, healthy lifestyle beliefs, and healthy lifestyle behaviors using valid and reliable scales. RESULTS: Compared with the screening and referral only group, participants in the intervention group had greater reductions in anxiety and depression and significantly greater increases in healthy lifestyle beliefs and behaviors at 3 and 6&#x2009;months post-intervention. After controlling baseline risk, the intervention group had a lower risk of suicidal ideation than the screening and referral group at 3&#x2009;months (relative risk ratio [RRR]&#x2009;=&#x2009;0.717; 95% CI: 0.320-1.606) and 6&#x2009;months (RRR&#x2009;=&#x2009;0.329; 95% CI: 0.101-1.072). The intervention group also had a significantly lower risk of burnout at 6&#x2009;months (RRR: 0.698, 95% CI: 0.528, 0.929, p&#x2009;=&#x2009;0.012). Nurses who completed more MBS sessions had less suicidal ideation at 6&#x2009;months and those who completed more MBS skills-building activities had less burnout at 3 and 6&#x2009;months. LINKING ACTION TO EVIDENCE: Integrating psychologically safe mental health screening combined with the scalable online CBT-based intervention, MBS, can produce sustained improvements in burnout, mental health symptoms, including suicidality, and healthy lifestyle beliefs and behaviors among nurses experiencing mental distress.

Humans

Compound muscle action potential amplitudes in newborn screen positive spinal muscular atrophy.

OBJECTIVE: To evaluate the utility of compound muscle action potential (CMAP) amplitudes as biomarkers of disease severity in newborn screening (NBS)-positive infants with spinal muscular atrophy (SMA). METHODS: We conducted a retrospective review of 21 infants identified through SMA NBS (11 with 2 SMN2 copies and 10 with 3 SMN2 copies). Baseline and serial right median, ulnar, and fibular motor nerve CMAP amplitudes (millivolts, mV) were obtained during the study. Functional outcomes were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND). RESULTS: At baseline, infants with 2 SMN2 copies demonstrated significantly lower median, ulnar, and fibular CMAP amplitudes compared with infants with 3 SMN2 copies (p&#xa0;<&#xa0;0.05). In contrast, baseline CHOP-INTEND scores did not differ significantly between the two groups. Prior to genetic confirmation, a right median CMAP amplitude&#xa0;&#x2265;3.2&#xa0;mV predicted&#xa0;&#x2265;3 SMN2 copies. Following treatment, right median and fibular CMAP amplitudes demonstrated significant improvement over time, including in analyses accounting for SMN2 copies number. CONCLUSION: CMAP amplitudes obtained from multiple upper- and lower-extremity motor nerves provided objective electrophysiological measures that distinguished infants with two versus three SMN2 copies, despite similar baseline CHOP-INTEND scores. Furthermore, CMAP abnormalities were detectable in some cases before confirmatory genetic testing results became available. Serial CMAP measurements demonstrated significant longitudinal changes following treatment, whereas functional assessments approached ceiling values, supporting the potential value of electrophysiological monitoring in the era of disease-modifying therapies. SIGNIFICANCE: CMAP assessment is a useful adjunct in the evaluation of infants identified through SMA NBS.

Humans

Stage shift, histological differentiation, and survival patterns of lung squamous cell carcinoma versus adenocarcinoma in low-dose CT screening.

BACKGROUND: Whether LDCT-associated stage shift translates into similar survival patterns across lung cancer histologies remains uncertain. We compared stage shift, histological differentiation, tumor characteristics, and survival between lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) in the National Lung Screening Trial. METHODS: Among participants diagnosed with LUSC or LUAD, stage distribution and histological differentiation were compared between LDCT and chest X-ray (CXR) arms. Survival among diagnosed cases was measured from randomization. Multivariable models tested screening arm-by-histology interactions. Screen-detected LDCT tumors were compared by histology. RESULTS: During 6.5 years of median follow-up, 498 LUAD and 249 LUSC cases were diagnosed in the LDCT arm, and 374 and 212, respectively, were diagnosed in the CXR arm. LDCT was associated with higher odds of stage I disease for LUAD (adjusted odds ratio [aOR], 2.48; 95% CI 1.88-3.28) and LUSC (aOR, 1.71; 95% CI 1.17-2.48), without significant interaction (P&#x202f;=&#x202f;0.116). LDCT was associated with lower hazard of lung cancer-specific death among diagnosed LUAD cases (adjusted hazard ratio [aHR], 0.54; 95% CI 0.43-0.66), but not among diagnosed LUSC cases (aHR, 1.04; 95% CI 0.78-1.39; P for interaction<0.001). LUSC had lower screening sensitivity, more frequent detection in annual screening rounds, greater prediagnostic tumor size increase, and fewer well-differentiated stage I tumors than LUAD. CONCLUSION: LDCT was associated with stage shift for both subtypes, but favorable survival patterns among diagnosed cases were mainly observed for LUAD. Lower screening sensitivity, greater prediagnostic tumor size increase, and poorer histological differentiation may help explain why stage shift did not translate into similar survival patterns for LUSC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00047385.

Humans

Predictive Validity of Violence Screening Tools in Emergency and Psychiatric Services: A Systematic Review.

Violence against healthcare staff, including a threat or an act of violence toward people during their work, poses a physical and psychological risk to workers internationally. Screening is an important strategy in preventing violence against healthcare professionals. The aim of this systematic review was to synthesize evidence on the predictive validity of risk assessment tools used to screen for violence and aggression risk toward healthcare workers in emergency and psychiatric departments (PD). Primary studies that examined the predictive validity of risk assessment tools for workplace violence were identified via a systematic search of Medline, PsycINFO, Embase, and the Cochrane databases. There were 62 eligible studies, ten of which had a lower risk of bias (RoB). Those studies with high RoB were primarily due to a failure to present calibration measures as part of the analysis. All included studies adopted a longitudinal design and were conducted in PDs. The ten highest-quality studies reported on eight different instruments, four of which showed acceptable to outstanding predictive performance. The Dynamic Appraisal of Situational Aggression and the Br&#xf8;set Violence Checklist showed the best predictive performance; they were also validated in emergency departments and are best suited for short-term risk prediction. We recommend that the selection of a risk assessment tool should consider the following: (a) the target population, (b) the violence operationalization, and (c) the purpose of the monitoring. We note that the use of a screening tool should be a part of a multicomponent strategy to ensure staff safety.

Humans

Screening for neurofibromatosis type 1-related optic pathway gliomas: a systematic review.

BACKGROUND: Neurofibromatosis-type 1 (NF1) is a genetic disorder characterized by developing optic pathway gliomas (OPGs) in 15%-20% of patients with higher estimates where consanguinity is prevalent. Clinically, NF1-OPG might be unpredictable with the risk of OPG progression and visual impairment. The optimal time for screening is controversial. We aim to identify the mean/median age at diagnosis of NF1-OPG and its clinical spectrum. METHODS: A systematic review of PubMed, Web of Science, and Embase databases was conducted for English-language publications from January 1993 to October 2025, exploring the visual screening of OPGs in NF1 patients, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews (PROSPERO ID: CRD420251036244). Inclusion criteria focused on studies reporting the age at OPG diagnosis and visual manifestations in NF1 patients. Data were extracted on demographics, age at NF1 and OPG diagnosis, tumour location (using the Dodge classification), and presenting symptoms. Sixteen studies met the inclusion criteria. RESULTS: Among 4 739 NF1 patients, 818 had OPGs, with prevalence ranging from 4.2% to 46.7%. The age at NF1 diagnosis ranged from 0 to 132 months (mean: 18-38 months), and at OPG diagnosis from 0-240 months (median: 29-58 months). Approximately 58.4% of OPGs were asymptomatic, and 25% were above the age of 5 years. Among symptomatic patients, the most frequent presentations included decreased visual acuity (62%), abnormal optic disc (45%), proptosis (20%), strabismus (12%), and visual field defects (7%). CONCLUSIONS: NF1-related OPGs typically present early within 6 years of age. Early ophthalmologic and/or radiologic screening at the time of NF1 diagnosis enhances the detection of silent OPGs.

Humans

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12&#x202f;cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B)&#x202f;&#x2248;&#x202f;9, coefficient of variance (CV)&#x202f;<&#x202f;10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus

Bioactive peptides for meat quality and preservation: Integrating peptidomics and computational screening.

Bioactive peptides generated from meat proteins, fermented meat products, and slaughter by-products have attracted increasing attention as functional molecules for improving meat quality and preservation. In meat systems, peptides can be produced through endogenous postmortem proteolysis, microbial fermentation, gastrointestinal digestion, or controlled enzymatic hydrolysis of underutilized animal by-products. These peptides are closely associated with key meat science endpoints, including postmortem tenderization, oxidative stability, color retention, flavor development, microbial inhibition, and the valorization of processing by-products. However, although high-resolution peptidomics has greatly expanded the identification of meat-derived peptide sequences, their translation into practical meat applications remains limited by matrix interactions, processing stability, sensory constraints, safety concerns, and insufficient validation in real meat systems. This review synthesizes recent advances in meat-related peptidomics and computational screening, including sequence-based prediction, machine learning, molecular docking, molecular dynamics, stability assessment, and safety-oriented filtering. Particular attention is given to how these approaches can prioritize peptides with antioxidant, antimicrobial, flavor-modulating, and preservation-related functions under meat-specific technological constraints. By integrating peptide generation pathways, mass spectrometry-based identification, in silico prioritization, and meat quality endpoints, this review proposes a stage-gated framework for translating meat-derived bioactive peptides from discovery to application. Future research should strengthen matrix-specific validation, standardized peptidomic reporting, and safety assessment to support the use of bioactive peptides in meat quality improvement, clean-label preservation, and circular utilization of meat industry by-products.

Animals

Self-Report Health Screening Tools in Female Athletes: A Systematic Review of Domain Coverage, Validation, and Use Across Participation Levels.

BACKGROUND: Female athlete health encompasses multiple interconnected domains; however, the self-report screening tools used to assess these domains have not been comprehensively synthesised. OBJECTIVE: To systematically identify self-report health screening tools used to assess female athlete health, map domain coverage, determine validation reporting, and describe application across participation levels. METHODS: This systematic review was pre-registered with PROSPERO ( CRD420251056910 ) and conducted in accordance with PRISMA guidelines. Four databases (PubMed, MEDLINE, SPORTDiscus and Web of Science) were searched from inception to January 2026 using female health and screening-related terms. Methodological quality was appraised using Joanna Briggs Institute and National Institutes of Health tools, and findings were synthesised descriptively. Eligible, peer-reviewed studies reported the use, development or validation of self-report health screening tools assessing one or more domains relevant to female health applied in female athlete populations, spanning recreational through elite participation levels. All sports and activities were included. The search was restricted to English language with no date limits. RESULTS: In total, 360 studies (1990-2026) representing 134,506 female participants spanning recreational to elite sport and 273 screening tools were included. Mental health (n&#x2009;=&#x2009;77, 34.1%), disordered eating (n&#x2009;=&#x2009;33, 14.6%) and body image (n&#x2009;=&#x2009;30, 13.3%) predominated. Domains related to female health, including menstrual health, pelvic floor health, pregnancy/postpartum and breast health were comparatively underrepresented. Most&#xa0;studies reported tools were used for risk identification (n&#x2009;=&#x2009;323,&#xa0;80.3%). Validation reporting was inconsistent, with half (n&#x2009;=&#x2009;180,&#xa0;50%) reporting use of at least one validated tool. Tool use was concentrated in professional and elite sport, with limited inclusion of recreational, masters and disability athlete cohorts. Health literacy constructs were explicitly&#xa0;assessed in 12.5% of studies&#xa0;(n&#x2009;=&#x2009;45). CONCLUSIONS: Health screening in female athlete populations remains fragmented and uneven in domain coverage, with inconsistent validation reporting. Development of integrated, multi-domain and contextually inclusive screening frameworks is warranted.

Journal Article

Performance of AI-Based Screening Tools for Obstructive Sleep Apnea Across Apnea-Hypopnea Index Thresholds: Systematic Review and Meta-Analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent but remains substantially underdiagnosed. Polysomnography (PSG) is the reference standard, but its cost and limited availability constrain large-scale case identification. AI-based screening tools may support risk stratification and referral prioritization, but their diagnostic accuracy across apnea-hypopnea index (AHI) thresholds remains uncertain. OBJECTIVE: This review aimed to systematically evaluate the diagnostic accuracy of AI-based OSA screening tools at AHI thresholds of &#x2265;5, &#x2265;15, and &#x2265;30 events/hour, with emphasis on models using non-PSG-derived inputs. METHODS: PubMed, Embase, Scopus, and Web of Science were searched for studies published from January 1, 2016, to May 3, 2026. Eligible studies included adults evaluated for suspected OSA or recruited from population-based cohorts, assessed AI-based models intended or interpretable for OSA screening, risk prediction, or screening-oriented severity classification, used PSG as the reference standard, and reported sufficient data to construct or reconstruct 2&#xd7;2 contingency tables. Diagnostic accuracy was synthesized separately by AHI threshold and input source using bivariate random-effects models, with 95% CIs and prediction intervals (PIs). Risk of bias and certainty of evidence were assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation), respectively. RESULTS: A total of 60 studies were included, of which 47 contributed data to the meta-analysis. At AHI thresholds of &#x2265;5, &#x2265;15, and &#x2265;30 events/hour, pooled sensitivities were 0.94 (95% CI 0.92-0.96; 95% PI 0.71-0.99), 0.87 (95% CI 0.84-0.89; 95% PI 0.66-0.96), and 0.83 (95% CI 0.79-0.87; 95% PI 0.61-0.94), respectively; the corresponding specificities were 0.77 (95% CI 0.69-0.84; 95% PI 0.30-0.96), 0.81 (95% CI 0.75-0.85; 95% PI 0.39-0.96), and 0.91 (95% CI 0.87-0.94; 95% PI 0.55-0.99), respectively. The corresponding areas under the summary receiver operating characteristic curves were 0.943, 0.907, and 0.920. For non-PSG-derived tools, sensitivities were 0.92, 0.85, and 0.81, and specificities were 0.70, 0.74, and 0.85 at the 3 thresholds, respectively. For PSG-derived models, sensitivities were 0.96, 0.90, and 0.85, and specificities were 0.82, 0.88, and 0.96, respectively. Exploratory subgroup analyses suggested performance variation across selected study and model characteristics, including region, algorithmic framework, data source, and validation method. CONCLUSIONS: AI-based tools showed generally favorable screening performance for OSA across clinically relevant AHI thresholds, although wide PIs suggest variable performance across future comparable populations and settings. By synthesizing diagnostic accuracy across 3 AHI thresholds and distinguishing non-PSG-derived from PSG-derived models, this review extends previous broad or modality-specific reviews and offers a clinically interpretable, pathway-specific basis for linking model performance to intended use. The findings may clarify potential roles for non-PSG-derived tools in front-end screening and referral prioritization and for PSG-derived models in reduced-channel assessment and sleep-laboratory workflow support. Given substantial heterogeneity, limited external validation, and low or very low certainty of evidence, prospective validation is needed before routine implementation.

Humans

Behaviourally informed text message reminders to increase cervical screening attendance in people with severe mental illness: the OPTIMISE pilot randomised controlled trial.

OBJECTIVES: This study assessed the feasibility of both the delivery and evaluation of 'enhanced' (behaviourally informed) text message reminders containing links to existing co-designed resources supporting decision-making for people with severe mental illness (SMI) regarding attendance of cervical screening. DESIGN: A pilot randomised controlled trial (RCT). SETTING: 13 General Practice (GP) practices in London were recruited. PARTICIPANTS: GP practices identified people with SMI aged 24-64 years who were overdue cervical screening. Target sample size was 120 participants (60 per arm) based on existing guidance for pilot trials. INTERVENTION: In March 2025, participants were randomised (1:1) to receive either the enhanced (intervention) or the standard (control) SMS reminder. PRIMARY AND SECONDARY OUTCOME MEASURES: 18 weeks later, feasibility outcomes were collected (primary outcomes) and data analysis for a definitive RCT was rehearsed (secondary outcome). RESULTS: Of the 150 participants across 13 GP practices that were randomised (n=75 per arm), 132 (88%) texts delivered (intervention n=64/75 (85%), control n=68/75 (91%)). 10 practices (76.9%) provided follow-up data for 102 participants (intervention n=50, control n=52). Five participants (intervention n=4, control n=1) attended screening within the trial period. Participant survey response rate was low (9/132 (7%), intervention n=5, control n=4). Both SMS messages were low cost, with the intervention SMS a 50% higher cost to deliver (7.5p vs 5p per SMS). Primary feasibility measures of recruitment rate of GP practices (27%), retention of GP practices (77%) and participants (100%), SMS delivery (88%) and data completeness (64%) indicated viability, although survey response rate (7%) did not. CONCLUSIONS: Achieving adequate recruitment and retention, data completeness and comparable groups is viable with some amendments, although an alternative method is required to assess fidelity. Behaviourally informed SMS reminders are feasible to deliver to people with SMI, although it is uncertain if the extra resources are accessed and used. With changes to data collection, a definitive trial could be feasible. Given the low observed cervical screening attendance, additional intervention is needed for this group. TRIAL REGISTRATION NUMBER: ISRCTN12558681.

Humans

Reliability-aware hierarchical learning for Chagas disease screening from 12-lead ECGs: tackling label uncertainty and class imbalance.

Objective.Chagas disease, a neglected tropical disease (NTD) with significant cardiovascular impact, remains underdiagnosed in resource-limited regions. Electrocardiogram (ECG) screening offers a low-cost tool for detecting cardiac involvement, yet algorithm development is challenged by label noise, data scarcity, and the latent nature of infection. This study proposes a robust ECG-based screening framework that explicitly addresses these constraints.Approach.We introduce aReliability-Aware Hierarchical Learningstrategy that calibrates supervision according to data provenance, prioritizing serology-confirmed labels over noisy self-reports. To mitigate data scarcity, we compare a specialized convolutional neural network (CNN) trained from scratch with a transfer learning approach based on a Spatio-Temporal ECG foundation Model (FM). Performance is evaluated across varying data scales, and the representation structure is analyzed to interpret model behavior.Main results.On the official hidden test set of the George B. Moody PhysioNet/Computing in Cardiology Challenge 2025, our approach achieved a Challenge Score of 0.163. We observe that while the specialized CNN performs competitively in data-rich regimes, the FM exhibits superior robustness in extreme low-resource settings. Furthermore, performance reaches a plateau imposed by underlying disease physiology. Bimodal score distributions suggest that models distinguish established cardiomyopathy from indeterminate infection, which remains electrophysiologically indistinguishable from healthy controls.Significance.These findings clarify both the potential and intrinsic limits of ECG-based AI screening for NTD-associated cardiac involvement. Reliability-aware supervision and data-efficient transfer learning provide a practical framework toward scalable and clinically meaningful ECG screening systems in resource-constrained environments.

Humans

Evaluation of three Aspergillus antibody assays for screening of chronic pulmonary aspergillosis: prospective diagnostic accuracy study.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is a frequent complication of pulmonary tuberculosis (PTB), particularly in high-burden settings where access to reliable serological diagnostics remains limited. We evaluated the diagnostic performance of two immunochromatographic technology (ICT) lateral flow assays (LFAs) and an ELISA for CPA screening among patients with active or previously treated PTB. METHODS: In this two-year prospective multicentre diagnostic evaluation, serum from adults with prior or active PTB was tested using the Era Biology Aspergillus IgG ICT LFA, LDBio Aspergillus IgG/IgM ICT LFA, and Bordier Aspergillus fumigatus IgG ELISA. CPA diagnosis was established using a consensus composite reference standard incorporating clinical, immunological, radiological, and microbiological criteria. The Bordier ELISA was used as part of the immunological component of the consensus CPA diagnosis, with a cutoff optical density of &#x2265;1.0. Diagnostic accuracy, agreement statistics, receiver operating characteristic analysis, and latent class analysis (LCA) were performed. RESULTS: Among 340 participants, 24 (7.06%) had CPA. Proportion of participants with positive antibody tests among all tested individuals were 6.76% for LDBio ICT LFA, 20.0% for Era Biology ICT LFA, and 11.47% for Bordier ELISA. Against consensus CPA diagnosis, Bordier ELISA showed 87.50% sensitivity and 94.30% specificity, LDBio ICT LFA 58.33% sensitivity and 97.15% specificity, and Era Biology LFA 66.67% sensitivity and 83.54% specificity. LCA estimated CPA prevalence at 7.72%. LCA-derived sensitivities and specificities were 86.58% and 99.92% for LDBio ICT LFA, 83.39% and 85.31% for Era Biology LFA, and 79.10% and 94.19% for Bordier ELISA. CONCLUSIONS: The Bordier ELISA showed high sensitivity and specificity, while the LDBio ICT LFA demonstrated very high specificity with strong LCA-derived performance. These findings support the use of ELISA for laboratory diagnosis and ICT as a point-of-care screening tool for CPA in resource-limited settings. Era Biology Aspergillus IgG LFA demonstrated moderate sensitivity and acceptable diagnostic performance, indicating its potential utility as a supplementary screening assay for CPA in settings where rapid, point-of-care testing is required.

Humans

A transcription factor-focused CRISPR screen identifies SKI as a BCL11A-independent repressor of &#x3b6;-globin.

The regulation of &#x3b1;-like globin genes, particularly the embryonic &#x3b6;-globin gene (HBZ), remains incompletely understood. To identify transcriptional regulators of HBZ, we establish a GFP reporter system based on the HBZ-P2A-GFP allele in erythroid cell lines and conduct a CRISPR/Cas9 screen targeting 1639 transcription factors. This screen identifies SKI as a potent HBZ repressor. Functional validation shows that SKI loss increases HBZ expression without impairing erythropoiesis, whereas SKI overexpression suppresses HBZ. Tet-on-inducible SKI overexpression and auxin-inducible SKI degradation indicate that SKI rapidly represses HBZ transcription. Transcriptome profiling further reveals that SKI deletion activates HBZ while minimally affecting other erythroid genes. Mechanistically, genome-wide occupancy analyses show that SKI binds the distal enhancers HS-10 and HS-40, with partial co-occupancy by BCL11A. Despite this overlap, dual knockout of SKI and BCL11A synergistically increases HBZ expression, as does base editing of the SKI-binding site within HS-10. We also identify a naturally occurring variant (chr16:193207G>A) within this enhancer in &#x3b1;-thalassemia patients with elevated &#x3b6;-globin levels. Together, these findings establish SKI as a direct, BCL11A-independent transcriptional repressor of &#x3b6;-globin. This work advances our understanding of globin gene regulation and suggests targeted &#x3b6;-globin reactivation as a potential therapeutic strategy for &#x3b1;-thalassemia.

Enhancer

In vivo genome-wide CRISPR screens identify FOXR1 as a suppressor of CD8+ T cell antitumor immunity.

T cell dysfunction critically limits the efficacy of T cell-based immunotherapies in solid tumors, yet the intrinsic regulators of T cell dysfunction remain incompletely understood. Through an in vivo genome-wide CRISPR screen in tumor-infiltrating CD8+ T cells, we identified Forkhead Box R1 (FOXR1) as a potent transcriptional suppressor of CD8+ T cell effector functions. Genetic ablation of FOXR1 significantly enhanced cytokine production and cytotoxic capacity in both murine and human CD8+ T cells, whereas its overexpression impaired T cell activation and effector molecule expression. Mechanistically, multiomics integration of RNA-seq, CUT&Tag-seq, and ATAC-seq revealed that FOXR1 binds directly to promoter regions of key effector genes, including IL2, GZMB, and PRF1, and represses their expression. Importantly, FOXR1 deletion in human anti-CD19 CAR T cells improved their efficacy against solid tumors, demonstrating that FOXR1 is a checkpoint of T cell effector function and targeting FOXR1 is a promising strategy to enhance CAR T cell efficacy against solid tumors.

Animals