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PubMed2022

Patient and provider perspectives on polygenic risk scores: implications for clinical reporting and utilization.

BACKGROUND: Polygenic risk scores (PRS), which offer information about genomic risk for common diseases, have been proposed for clinical implementation. The ways in which PRS information may influence a patient's health trajectory depend on how both the patient and their primary care provider (PCP) interpret and act on PRS information. We aimed to probe patient and PCP responses to PRS clinical reporting choices METHODS: Qualitative semi-structured interviews of both patients (N=25) and PCPs (N=21) exploring responses to mock PRS clinical reports of two different designs: binary and continuous representations of PRS. RESULTS: Many patients did not understand the numbers representing risk, with high numeracy patients being the exception. However, all the patients still understood a key takeaway that they should ask their PCP about actions to lower their disease risk. PCPs described a diverse range of heuristics they would use to interpret and act on PRS information. Three separate use cases for PRS emerged: to aid in gray-area clinical decision-making, to encourage patients to do what PCPs think patients should be doing anyway (such as exercising regularly), and to identify previously unrecognized high-risk patients. PCPs indicated that receiving "below average risk" information could be both beneficial and potentially harmful, depending on the use case. For "increased risk" patients, PCPs were favorable towards integrating PRS information into their practice, though some would only act in the presence of evidence-based guidelines. PCPs describe the report as more than a way to convey information, viewing it as something to structure the whole interaction with the patient. Both patients and PCPs preferred the continuous over the binary representation of PRS (23/25 and 17/21, respectively). We offer recommendations for the developers of PRS to consider for PRS clinical report design in the light of these patient and PCP viewpoints. CONCLUSIONS: PCPs saw PRS information as a natural extension of their current practice. The most pressing gap for PRS implementation is evidence for clinical utility. Careful clinical report design can help ensure that benefits are realized and harms are minimized.

Clinical Decision-Making↗

PubMed2025

Image-guided biopsy of breast lesions-when to use what biopsy technique.

In recent years, minimally invasive diagnostic options for breast lesions have expanded, but consensus on optimal biopsy techniques and imaging combinations remains lacking. This study, driven by an adapted RAND-UCLA Appropriateness Method and insights from eight experts in breast biopsy from across the world, aims to create consensus for selecting biopsy techniques. Highlighted findings suggest Vacuum-Assisted Biopsy (VAB) for lesions visible exclusively at mammography/tomosynthesis (with or without contrast enhancement) or MRI. Core-needle biopsy (CNB) takes precedence for masses over 5 mm visible under US. The selection of other biopsy techniques during US-guided procedures depends on lesion type, size, and sampling indication. VAB is preferred for smaller masses (< 5 mm), complex cystic and solid lesions with small solid parts, small intraductal masses, architectural distortions, and calcifications visible on US. In re-biopsy scenarios for inconclusive findings or high-risk lesions, the panel suggests two VAB extensions: Extended Vacuum-Assisted Biopsy (EVAB) for unambiguous lesion classification and Vacuum-Assisted Excision (VAE) for complete lesion removal. Furthermore, the panel provides detailed input on how to handle specific cases, such as re-biopsy for lobular neoplasia, flat epithelial atypia and atypical ductal hyperplasia. Surgical excision is advised for DCIS and benign or borderline phyllodes tumors found through initial CNB or VAB. In conclusion, an international expert group formulated recommendations on diagnostic breast biopsies under image guidance, aiming to ensure accurate diagnosis worldwide by providing practical advice on needle selection and biopsy approach. KEY POINTS: Evidence-based literature on the preferred biopsy technique and imaging combination for the diagnosis of breast lesions is sparse, and a general consensus is not available. The selection of biopsy technique for different image-guided procedures depends on lesion type, size, and sampling indication. This international expert panel consensus statement addresses standard approaches for varying biopsy indications.

Breast cancer↗

PubMed2026

A descriptive analysis of Streptococcus suis-associated disease in Irish pigs from 2010 to 2024: serotypes, pathology, and antimicrobial resistance.

BACKGROUND: Streptococcus suis is a major cause of respiratory and systemic diseases in post-weaned pigs, leading to significant production losses and animal welfare concerns. This study provides the first long-term national level analysis of Streptococcus suis-associated disease (SSAD) in the Republic of Ireland. We examined the pig diagnostic submissions, characterised serotype distribution, antimicrobial susceptibility, and co-infection patterns from 2010 to 2024. RESULTS: The findings confirm that serotypes 9 and 2 or 1/2 were most frequently associated with disease. We observed a significant shift in recent years where serotype 9 has surpassed serotype 2 or 1/2 in number of occurrences. S. suis was frequently co-detected with viral pathogens including porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2, and swine influenza virus (SIV), as well as bacterial pathogens such as Actinobacillus pleuropneumonia and Pasteurella multocida, typically from pneumonic lungs. While resistance to tetracycline and erythromycin was high (44.4% to 65.8%), isolates remained susceptible to first-line beta-lactam antibiotics such as penicillin (7.9% resistance), ampicillin (5.5% resistance) and amoxycillin/clavulanate (0% resistance). CONCLUSION: The observed heterogeneity between and within herds challenges successful implementation of vaccination and highlights the need for ongoing disease monitoring. These findings provide the first in-depth assessment of SSAD in Ireland's pig population which will offer valuable insights for future surveillance efforts, including genomic studies and supporting evidence-based strategies and vaccine selection for controlling S. suis in Irish pig sector.

Ireland↗

PubMed2026

What influenced the use of embedded genetic expertise by non-genetic clinicians: a qualitative study using the diffusion of innovations theory and theoretical domains framework.

BACKGROUND: While employing change agents is a widely used strategy to support implementation of evidence-based practices in healthcare, the perspectives of the target users of this intervention are under-explored. Within a genomic care setting in Australia, we examined non-genetic clinicians' views of and experience with embedded genetic counsellors employed as external change agents to support the adoption of genomics in clinical care. METHODS: We conducted qualitative interviews with 16 non-genetic healthcare professionals involved in different models of genomic care, all of which employed genetic counsellors as external change agents to provide embedded genetic expertise and support in non-genetic specialty clinics. The Diffusion of Innovations (DOI) theory and the Theoretical Domains Framework (TDF) were drawn upon to guide the study design and data analysis to explore the enablers/barriers to non-genetic clinicians' use of genetic expertise and the wider implementation context of the change agent approach. RESULTS: The TDF domain 'Belief about Consequences' was a positive influence on non-genetic specialists' view of the embedded change agents, when they believed that the change agents positively impacted patient outcomes and the clinicians' knowledge and practice of using genomics in routine care. Meanwhile, major barriers were related to 'Environmental Context & Resources,' e.g. time constraints and logistic hurdles of involving change agents. Perceived attributes related to 'complexity' and 'observability' of genetic expertise were critical factors influencing the decision to put the support to actual use, impacting the diffusion of the genomic innovation. CONCLUSIONS: Our study offers insights into behavioural influences and contextual conditions shaping clinicians' decisions to interact with genetic counsellor change agents and incorporate (or not) their expertise into their routine care. Such understandings can inform future design and implementation of interventions that use change agents to support the adoption of innovations, such as genomics, effectively and sustainably.

Journal Article↗

PubMed2026

Approaches to thyroid nodules in paediatric cancer predisposition syndromes.

OBJECTIVE: The objective of this work was to summarize current evidence and practical management considerations for thyroid nodules in children and adolescents with cancer predisposition syndromes (CPSs), focusing on follicular cell-derived nodules and non-medullary thyroid carcinoma (NMTC). METHODS: We synthesized current paediatric guideline recommendations and recent cohort, pathology, and molecular studies addressing CPS-associated nodular thyroid disease, including PTEN hamartoma tumour syndrome (PHTS), DICER1 syndrome, familial adenomatous polyposis, and related endocrine neoplasia syndromes. RESULTS: Evidence quantifying syndrome-stratified malignancy risk among paediatric CPS patients presenting with nodules remains limited and is largely derived from mixed-age or retrospectively ascertained cohorts with surveillance and verification bias. High-resolution ultrasound (US) is central to risk stratification. US-guided fine-needle aspiration (FNA) is a cornerstone of evaluation yet frequently yields indeterminate results, particularly in follicular-patterned and encapsulated lesions (e.g. PHTS and DICER1 syndrome), and sampling error is accentuated in polyclonal multinodular disease. Molecular testing may aid aetiologic clarification and, in selected settings, risk refinement. However, panels optimized for sporadic adult disease may have reduced 'rule-out' utility in CPSs. Biochemical assessment (TSH ± free thyroxine) complements imaging, while routine thyroglobulin is not recommended, and thyroid autoantibodies should be viewed as adjunctive rather than directive markers in CPSs. CONCLUSION: Management of thyroid nodules in paediatric CPSs is best approached through integrated, multidisciplinary risk assessment that combines expert ultrasound, context-aware cytology and molecular interpretation, and shared decision-making. This review proposes a CPS-adapted, multidisciplinary risk assessment framework and highlights the need for prospective multicentre registries and harmonized protocols to define syndrome-specific outcomes and evidence-based thresholds for surveillance and intervention.

Humans↗

PubMed2026

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 α=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; χ21=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; η2=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↗

PubMed2026

Effectiveness of a Web-Based Educational eHealth Platform on Women's Health Literacy About Phthalate Exposure: Randomized Controlled Trial.

BACKGROUND: Phthalates are environmental endocrine-disrupting chemicals widely used in plastics, cosmetics, food packaging, and personal care products. Women may experience frequent exposure through everyday consumer and household products. Improving phthalate-related health literacy may support informed exposure-reduction decisions; however, conventional health education provides limited opportunities for repeated, interactive, and individually tailored learning. OBJECTIVE: This randomized controlled trial evaluated the effectiveness of an eHealth educational intervention (Phthalates Free) in improving women's overall and domain-specific phthalate-related health literacy and examined the association between platform engagement and health literacy outcomes. METHODS: A double-blind randomized controlled trial was conducted in the outpatient department of a regional teaching hospital in Taipei, Taiwan. A total of 114 women were randomly assigned to an intervention group (n=58) receiving a 6-month eHealth platform-based education program and a control group (n=56) receiving conventional paper-based education. Assessments were conducted at baseline (T0), 3 months (T1), and 6 months (T2). The Phthalate Health Literacy Scale (10 items; α=.90, content validity index=0.93) measured overall and domain-specific literacy (health care, disease prevention, and health promotion). Longitudinal outcomes were analyzed using generalized estimating equations based on all available observations according to participants' original randomized assignments, with adjustment for waist circumference and pregnancy history. Analysis of covariance (ANCOVA) was used to compare 6-month outcomes after adjustment for baseline scores. Platform engagement and perceived usability were assessed using back-end analytics and the System Usability Scale (SUS). RESULTS: At 6 months, the intervention group showed a significantly greater increase in total health literacy than the control group (+9.93 points, Wald χ²1=17.74; P<.001). Domain analyses revealed significant improvements in health care (+1.52; P=.001), disease prevention (+1.32; P=.001), and health promotion (+1.12; P=.001) domains. ANCOVA confirmed the between-group difference at T2 after adjusting for baseline scores (F1,109=11.43; P=.001; adjusted mean difference=7.15, 95% CI 2.96-11.34). Engagement analysis showed that high-engagement users (n=10) scored significantly higher in overall health literacy (t55=-3.00; P=.004) and all domains than general users. The SUS results (mean 84.7, SD 5.2; n=46, 79.3%) indicated high perceived usability. CONCLUSIONS: The Phthalates Free eHealth educational intervention significantly improved women's overall and domain-specific health literacy over 6 months. Higher platform engagement was associated with better health literacy outcomes. The intervention may serve as a practical adjunct to nurse-led education in outpatient and community settings by providing accessible, continuous, and evidence-based guidance on reducing phthalate exposure.

Humans↗

PubMed2026

Double heterozygous germline pathogenic variants in patients referred to a tertiary cancer genetics clinic in Singapore.

BACKGROUND: The increasing use of multigene panel testing has led to a rise in the identification of double heterozygous (DH) pathogenic variants in cancer patients, although their frequency and clinical relevance remain poorly characterised, particularly in Asian populations. METHODS: We conducted a retrospective review of 5,178 patients referred to a tertiary cancer genetics clinic in Singapore. DH pathogenic variants were defined as the presence of two or more distinct pathogenic or likely pathogenic germline variants identified by multigene panel testing. Clinical, pathological, and family history data were reviewed and analysed using appropriate non-parametric and exact statistical methods. RESULTS: Among 2,802 index patients with available genetic test results, 593 (21.2%) carried at least one pathogenic/likely pathogenic variant. DH pathogenic variants were identified in 21 individuals (0.75%), of which 9 were patients with breast cancer, 10 with non-breast malignancies, and 2 were cancer-free. The frequency of multiple primary cancers was 26.3% in DH variant carriers, 23.3% in single variant carriers, and 16.5% in those with no pathogenic variants. The median ages of first cancer diagnosis were 47, 44, and 48 years. Several DH combinations involved moderate- or low-penetrance genes, and some clinically unsuspected variants were detected only through broad multigene testing. CONCLUSION: DH pathogenic variants represent a rare subgroup that is increasingly detected through multigene panel testing. Their phenotypic expression is variable, and the influence of additional pathogenic variants remains uncertain. Our findings emphasise the need for tailored genetic evaluation and further research to guide evidence-based management for this complex patient population.

Asia↗

PubMed2025

National strategies for screening neural tube defects in Saudi Arabia: activating prevention and early intervention.

BACKGROUND: Neural tube defects (NTDs) are serious congenital anomalies affecting the brain and spinal cord. Despite widespread folic acid supplementation and food fortification programs, regions such as Saudi Arabia have not experienced a proportional decline in NTD prevalence. This narrative review evaluates the multifactorial contributors to NTDs, focusing on the effectiveness of current prevention and screening strategies both globally and within Saudi Arabia. MATERIALS AND METHODS: A comparative methodology guided this review, drawing from studies published between 2000 and 2024 sourced from PubMed, Scopus, and the WHO library. Keywords included "neural tube defects," "folic acid supplementation," "screening programs," and "food fortification." While not a systematic review, PRISMA principles were loosely followed to ensure study relevance and rigor. RESULTS: Globally, countries like the United States, Canada, Chile, and Australia have implemented mandatory folic acid fortification and reported NTD reductions ranging from 19 to 78%. South Africa, for example, achieved a 66% decline in NTD-related deaths post-fortification. In Saudi Arabia, similar initiatives have been launched, including folic acid campaigns and food fortification. However, national-level data evaluating their impact remains sparse. Regional disparities in implementation, awareness, and access have limited the success of these measures. Although 80.1% of Saudi women reportedly understand the preventive role of folic acid, uptake and proper timing of supplementation remain inconsistent. Screening services, particularly in rural areas, are not uniformly accessible, reducing early detection rates. Unlike countries such as Australia and Chile, Saudi Arabia lacks a standardized system for tracking and evaluating NTD outcomes. CONCLUSION: This review concludes that while Saudi Arabia has adopted commendable preventive strategies, the absence of comprehensive data, policy enforcement, and public education limits their effectiveness. Strengthening national monitoring systems, ensuring equitable access to screening, and enforcing mandatory fortification policies modelled on successful international practices are critical. Adopting evidence-based policies supported by robust evaluation frameworks will be essential to reducing the burden of NTDs and improving maternal and child health outcomes in Saudi Arabia.

Humans↗

PubMed2026

Beyond the clinic: a community-embedded, multidomain framework for early detection of glaucoma.

Glaucoma remains one of the leading causes of acquired irreversible blindness worldwide, with normal-tension glaucoma representing the dominant subtype in Japan and several East Asian populations. The insidious, asymptomatic progression of this condition, combined with the demonstrated inadequacy of intraocular pressure alone as a screening criterion, creates a critical gap between disease burden and case detection. Population-based epidemiological studies consistently reveal that the majority of individuals with glaucoma are undiagnosed. Two responses have been suggested: incorporation of retinal imaging into annual health checkups, which warrants formal prospective evaluation, and characterization of individuals at higher risk - integrating genomic risk, oxidative stress biomarkers, systemic lifestyle factors, and ocular blood flow dynamics - which may help identify those in whom damage is most likely to occur. The principal contribution of this Perspective is therefore the implementation model rather than the individual screening components. We introduce the Living Lab ('neighborhood health lab'), a community co-creation platform established under the Japan Science and Technology Agency COI-NEXT 'Vision to Connect' hub at Tohoku University, as a scalable model for operationalizing this framework. Embedded within commercial retail environments, the Living Lab integrates non-invasive screening, longitudinal health data collection, and evidence-based health product development-exemplified by the Ronbun Recipe® concept-within a stakeholder-aligned ecosystem encompassing citizens, researchers, industry, and municipal authorities. Conceived as a platform for well-being rather than as a disease-specific screening service, it engages individuals who are asymptomatic, undiagnosed, and outside existing screening pathways, and who would not otherwise be assessed at all.

Humans↗

PubMed2026

Genetically Modified and Gene-Edited Organisms-Objectives, Public Perception and Applications.

Genetic modification and genome editing have become important tools in agriculture, animal production, biotechnology, and human medicine, but their safety and societal acceptance remain subjects of debate. This review examines genetically modified (GM) and gene-edited organisms, distinguishing transgenesis from precision genome editing technologies, including CRISPR/Cas9, base editing, and prime editing. Representative applications in crops, livestock, pharmaceutical production, and xenotransplantation are discussed, together with their regulatory framework and public perception. Current scientific assessments indicate that approved GM foods are not inherently more hazardous to human health than their conventional counterparts when evaluated case by case. Potential benefits include improved nutritional quality, biofortification, disease resistance, increased agricultural efficiency, production of therapeutic proteins, and applications in animal health and medicine. Possible concerns include allergenicity, toxicity, unintended genetic or phenotypic effects, altered nutritional composition, environmental consequences, animal welfare issues, and uncertainties associated with long-term or large-scale deployment. Public acceptance varies substantially according to geographical region, application, cultural and ethical considerations, regulatory environment, scientific literacy, and institutional trust. Overall, GM and gene-edited organisms should not be considered a homogeneous category. Their benefits, risks, and societal acceptability depend on the specific organism, genetic modification, intended trait, and context of use, supporting a balanced, evidence-based, and case-specific approach.

acceptance↗

PubMed2022

Comparison on Major Gene Mutations Related to Rifampicin and Isoniazid Resistance between Beijing and Non-Beijing Strains of Mycobacterium tuberculosis: A Systematic Review and Bayesian Meta-Analysis.

Objective: The Beijing strain of Mycobacterium tuberculosis (MTB) is controversially presented as the predominant genotype and is more drug resistant to rifampicin and isoniazid compared to the non-Beijing strain. We aimed to compare the major gene mutations related to rifampicin and isoniazid drug resistance between Beijing and non-Beijing genotypes, and to extract the best evidence using the evidence-based methods for improving the service of TB control programs based on genetics of MTB. Method: Literature was searched in Google Scholar, PubMed and CNKI Database. Data analysis was conducted in R software. The conventional and Bayesian random-effects models were employed for meta-analysis, combining the examinations of publication bias and sensitivity. Results: Of the 8785 strains in the pooled studies, 5225 were identified as Beijing strains and 3560 as non-Beijing strains. The maximum and minimum strain sizes were 876 and 55, respectively. The mutations prevalence of rpoB, katG, inhA and oxyR-ahpC in Beijing strains was 52.40% (2738/5225), 57.88% (2781/4805), 12.75% (454/3562) and 6.26% (108/1724), respectively, and that in non-Beijing strains was 26.12% (930/3560), 28.65% (834/2911), 10.67% (157/1472) and 7.21% (33/458), separately. The pooled posterior value of OR for the mutations of rpoB was 2.72 ((95% confidence interval (CI): 1.90, 3.94) times higher in Beijing than in non-Beijing strains. That value for katG was 3.22 (95% CI: 2.12, 4.90) times. The estimate for inhA was 1.41 (95% CI: 0.97, 2.08) times higher in the non-Beijing than in Beijing strains. That for oxyR-ahpC was 1.46 (95% CI: 0.87, 2.48) times. The principal patterns of the variants for the mutations of the four genes were rpoB S531L, katG S315T, inhA-15C > T and oxyR-ahpC intergenic region. Conclusion: The mutations in rpoB and katG genes in Beijing are significantly more common than that in non-Beijing strains of MTB. We do not have sufficient evidence to support that the prevalence of mutations of inhA and oxyR-ahpC is higher in non-Beijing than in Beijing strains, which provides a reference basis for clinical medication selection.

Isoniazid↗

PubMed2026

Gut Dysbiosis in Selected Gynecological Diseases Associated with Female Infertility: A Scoping Review.

Background/Objectives: Female infertility represents a significant public health issue. Available evidence supports the hypothesis that the gut microbiota may play an essential role in women's reproductive health and may serve as a diagnostic or prognostic biomarker in specific gynecological disorders. A substantial part of current research concerns disturbed communication between the hypothalamic-pituitary-ovarian axis and the gut microbiota, providing the basis for analyzing this phenomenon as the gut-ovary axis or the gut-vagina-ovary axis. The primary aim of this scoping review was to map the available evidence on the relationship between gut microbiota composition and female infertility, with particular emphasis on polycystic ovary syndrome (PCOS, currently polyendocrine metabolic ovarian syndrome, PMOS) endometriosis, and uterine fibroids. Methods: The review was conducted in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR). PubMed, Scopus, and Google Scholar were searched using terms related to gut microbiota, female infertility, PCOS, endometriosis, and uterine leiomyomas. Peer-reviewed publications in English published between 2015 and 2025 were considered. The included studies were descriptively synthesized to identify recurring microbiota patterns and research gaps. Results: The reviewed evidence indicates that gut dysbiosis may be associated with selected gynecological disorders affecting fertility, including PCOS, endometriosis, and uterine fibroids. The gut microbiome may have potential value as a biomarker supporting diagnosis, treatment selection, and prognosis. Conclusions: The gut microbiome represents a promising but still insufficiently validated area in the management of gynecological diseases associated with female infertility. Further high-quality clinical studies are needed to verify the effectiveness of microbiome-based therapies and to develop evidence-based guidelines for managing infertility associated with gut dysbiosis.

dysbiosis↗

PubMed2026

[State Changes and Stability Grading of Driver Genes in Non-small Cell Lung Cancer Based on Repeated NGS Testing].

BACKGROUND: Next-generation sequencing (NGS)-based driver gene testing has become a routine component of molecular subtyping and precision therapy for non-small cell lung cancer (NSCLC). Dynamic genomic monitoring facilitates early detection of resistance-related molecular alterations and informs timely therapeutic adjustments. However, standardized criteria for evaluating the stability of serial NGS testing are currently lacking, and the applicability of NGS using formalin-fixed paraffin-embedded (FFPE) specimens for dynamic monitoring remains poorly defined. This study aims to establish a stability grading system for driver gene status alterations based on repeated NGS testing, and to provide evidence-based support for clinical repeat biopsy strategies. METHODS: Data from 1232 patients with NSCLC who underwent two or more NGS tests on FFPE tissue specimens at Beijing Chest Hospital between June 2019 and April 2026 were collected retrospectively. Patients with an interval of ≥4 months between the initial and last tests were included to ensure the representativeness of temporal analysis, resulting in a main analysis cohort of 942 patients. The Kappa consistency test was used to evaluate the state stability of nine core driver genes [epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), mesenchymal‑epithelial transition factor (MET), rearranged during transfection (RET), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), erb‑b2 receptor tyrosine kinase 2 (ERBB2), and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA)] and to construct a five‑level grading system. Paired variant allele frequency (VAF) differences were compared using the Wilcoxon signed‑rank test. Independent influencing factors for mutation accumulation were identified by binary Logistic regression. RESULTS: The state stability of the nine genes was classified into five levels: EGFR showed high stability (Kappa=0.838), ROS1/ALK/KRAS good stability, BRAF/PIK3CA/RET moderate stability, and ERBB2 low stability, and MET showed high instability. MET exhibited the highest rate of state change (9.3%) with a raw observed agreement of 90.7%. Its Kappa value (0.172) was influenced by the low prevalence (3.7%) compression effect and should therefore be interpreted alongside the observed agreement (90.7%) and the prevalence-adjusted and bias-adjusted Kappa (PABAK). The VAF of PIK3CA increased significantly (P=0.005). T790M positivity increased from 5.8% to 10.8%, and 30 new C797S mutations were detected at the last test (13 with T790M, 17 without). The overall rate of new driver gene variants in the main cohort was 18.0%. Binary Logistic regression showed that a lower number of initial mutated genes was the only independent predictor of new variants [odds ratio (OR)=0.399, P<0.001], while sex and detection interval showed no independent association. CONCLUSIONS: A five level stability grading system for state changes of driver genes in NSCLC based on repeated NGS testing has been established. MET showed the most frequent state changes, which should be interpreted in conjunction with the prevalence effect. The VAF increase of PIK3CA is an observational finding, and its clinical significance requires further prospective validation. A lower initial mutation burden may reflect tumor clonal complexity and was associated with a higher likelihood of subsequent acquisition of new variants. FFPE based NGS is applicable for repeated testing at clinical treatment decision nodes.

Humans↗

PubMed2026

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↗

PubMed2026

The Effectiveness of Passive Half-Time Interventions on Simulated Second-Half Performance in Elite Youth Soccer Players.

The half-time period in soccer provides a potentially important window to implement short-duration interventions aimed at maintaining second-half performance. However, passive rest has been associated with a decline in subsequent physical and technical performance. While re-warm-up strategies are well studied, little is known about the efficacy of technology-based, passive recovery modalities, device-supported interventions that require minimal active movement or physical exertion from the athlete, during half-time intervals. This study examined whether percussive therapy, electrical muscle stimulation, and pneumatic compression can mitigate second-half performance decline in male adolescent soccer players. Forty-three academy-level players (17.5 ± 0.6 years) completed a simulated soccer protocol including the Loughborough Soccer Pass Test (LSPT), repeated 20-meter sprints, and completed Total Quality of Recovery (TQR) assessments before and after half-time. Participants were randomized into one of four intervention groups during the 15-minute half-time interval: Passive Rest (CON), Percussive Therapy (Theragun Pro; TG), EMS (PowerDot; PD), and Pneumatic Compression (RecoveryAir; COMP). Linear mixed-effects models assessed Time × Condition interactions for performance and recovery outcomes. Passive half-time rest led to significant deterioration in technical skill, sprint performance, and perceived recovery (p < .05) for the control group. TG and PD significantly improved technical performance (LSPT scores) compared to the control group (d = 0.65 and 0.72, respectively; p < .01). Furthermore, TG and COMP were effective at maintaining 20-meter sprint times (d = 0.58 and 0.49; p < .01), whereas the control group experienced significant slowing. Perceived recovery (TQR) scores significantly declined in the CON group from First Half to Second Half (16.5 ± 2.2 to 11.1 ± 2.3. However, this decline was significantly attenuated in all intervention groups: TG (17.5 ± 1.9 to 14.2 ± 1.9), PD (17.3 ± 1.9 to 15.1 ± 1.9), and COMP (17.6 ± 1.9 to 15.9 ± 2.0). Short-duration passive interventions during half-time can mitigate performance decline in adolescent soccer players. TG and EMS appear most effective for preserving technical skills, while COMP may support perceived recovery. These findings highlight practical strategies for optimizing in-game performance and inform evidence-based half-time protocols.

Humans↗

PubMed2026

Weight regain following discontinuation of glucagon-like peptide-1 receptor agonists in adults who are overweight or obese: a systematic review and meta-analysis.

OBJECTIVE: This study aims to explore the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on weight changes and the occurrence of adverse reactions in overweight or obese adults after drug withdrawal. METHODS: Computerized searches were conducted in evidence-based databases such as PubMed, Embase, Cochrane Library and Scopus. The search period was from the establishment of the database to December 2025. Collect randomised controlled trials (RCTs) and controlled trials on GLP-1RAs, including tirzepatide, semaglutide, liraglutide, and dulaglutide, for the treatment of overweight or obese adult patients. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias V2.0 tool provided by the Cochrane Collaboration, and meta-analysis was performed using the R programming language. RESULTS: A total of 699 studies were initially retrieved. Eventually, six studies involving 8,993 patients were included in the quantitative analysis, comprising 5,553 patients in the discontinuation group and 3,440 in the continued treatment group. The results of the meta-analysis showed that, compared with the continued treatment group, the weight difference in the discontinuation group was mean difference (MD) = 17.90%, 95% confidence interval (CI) [14.11-21.69], P < 0.0001. It can be seen that there was a significant rebound in weight after drug withdrawal, and there was statistical heterogeneity among the studies (P = 0.0082). Subgroup analysis further revealed that the weight rebound amplitude after discontinuation of tirzepatide was significantly higher than that of semaglutide. This result suggests that the differences in the mechanism of action of different GLP-1RAs may be the reason for the differences in weight changes after discontinuation. In addition, the percentage difference in body weight between after and before drug withdrawal was MD = 9.11%, 95% CI [7.91-10.30], P < 0.0001, further verifying the trend of weight rebound after drug withdrawal. The summary of adverse reaction reports analyzed and studied indicates that after drug withdrawal, the overall adverse reactions of patients decreased, gastrointestinal adverse reactions decreased, and the incidence of cardiovascular events was not affected by drug withdrawal. CONCLUSION: There is a significant weight rebound phenomenon after discontinuation of GLP-1RAs, and the rebound magnitudes vary among different types of drugs. At the same time, there is a risk of adverse reactions during the use of such drugs.

Humans↗

PubMed2026

What's the meta now? More updates on the problems with systematic reviews.

BACKGROUND: Systematic reviews are intended to provide trustworthy evidence synthesis, yet previous iterations of this living review have identified numerous recurring problems in their conduct and reporting. This article presents the third version and second update of the living systematic review examining issues raised across the academic literature. METHODS: Using consistent eligibility criteria and methods from earlier versions, literature searches were updated to May 2025. Eligible meta-research and editorial articles describing problems with systematic reviews were analyzed to identify emerging themes. Additionally, four basic indicators of methodological quality of the included meta-research were presented across review versions. RESULTS: The update included 209 additional articles. Critically low methodological quality and absence of protocols remained among the most frequently reported issues in systematic reviews across disciplines and journals but notably in evidence underpinning clinical practice guidelines. Spin in abstracts and conflicts of interest continued to be common. Apparent improvements in reporting quality were inconsistent, with modest gains in some full-text reporting but persistent deficiencies in abstracts. Authorship diversity of systematic reviews improved in gender representation but remained geographically concentrated in high-income countries, and primary research included in reviews similarly lacked global representativeness. The issue of misalignment between systematic review evidence bases and global burden of disease bring the total number of problems with systematic reviews to 69. Emerging use of automation and artificial intelligence was variably reported. Descriptive comparison of meta-research articles over the three versions of this living review suggests a greater proportion meeting basic quality indicators in more recent updates. CONCLUSION: Across successive updates, problems with systematic reviews remain widespread and consistent rather than isolated. Incremental reporting improvements coexist with persistent concerns about transparency, bias, and representativeness. Future efforts should prioritize evaluating interventions and aligning research incentives to support genuinely trustworthy evidence synthesis.

Humans↗