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PubMed2026

Impact of Physical Environment of Pediatric Inpatient Wards on Children: A Systematic Literature Review.

ObjectiveThe study aimed to examine empirical studies published between 2003 and 2025 to identify elements of physical environments influencing health outcomes and experiences of children and families.BackgroundIn the past 40 years, research has shown that the physical environment influences the health and well-being of patients in the healthcare environment. However, similar research in the context of "pediatric inpatient wards" remains underexplored.MethodsPubMed, Embase, Scopus, and Web of Science were used to identify relevant articles. All extracted articles underwent a three-step screening process using PRISMA. A total of 30 eligible articles were used for the analysis. The protocol is registered at PROSPERO (CRD42023408997).ResultsKey findings reveal positive and negative impacts of identified elements. Positive-effect elements include play spaces, space for parents, natural light, connections with nature, and so on, which promote comfort, healing, and emotional resilience. Conversely, negative-effect elements, such as noise, artificial lighting, uncomfortable temperature, and so on, contribute to stress and disrupted sleep. Mixed effects were observed for elements like art and television, which underscore the complexity of designing environments that address the diverse needs of different age groups and genders.ConclusionsThe review findings highlight significant knowledge gaps. The study also tries to bridge existing gaps between research and practice by systematically identifying environmental elements, offering actionable insights to architects, designers, healthcare providers, and policymakers. Future research must adopt rigorous, culturally inclusive approaches to advance the field of pediatric healthcare design and ensure equitable care across diverse sociocultural contexts.

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PubMed2026

Culture of infectious human norovirus isolated from live contaminated oysters.

Human noroviruses are a major cause of foodborne outbreaks worldwide. Filter-feeding shellfish, such as oysters, can bioaccumulate these viruses in their digestive tissue when grown in sewage-impacted coastal areas and are often implicated in norovirus foodborne outbreaks. Despite the high sensitivity of current molecular assays, these methods for norovirus detection in shellfish fail to distinguish between infectious and non-infectious particles. Assessing norovirus infectivity in shellfish remains a challenge due to the lack of suitable isolation methods that maintain capsid integrity. In this study, a protocol for isolating infectious norovirus from oyster tissues, based on chloroform-butanol elution and polyethylene glycol concentration (CB-PEG), was optimized for the recovery of human norovirus GI and GII. While CB-PEG method recovered various norovirus GI and GII genotypes, it was less efficient at the genomic level than a protocol based on proteinase K elution (adapted from ISO 15216) and showed genotype-dependent viral recovery rates. By optimizing the flocculation step, we improved the method's compatibility with human intestinal enteroid (HIE) cultures. Using this approach, we successfully quantified infectious norovirus GII.3 titers recovered from artificially-contaminated live oysters. Interestingly, infectious virus was better isolated following a freezing step of the digestive tissues, with titers ranging from 13 to 40 TCID50/mL for positive samples. In conclusion, this study established an optimized methodological approach for the relative quantification of infectious norovirus GII.3 in shellfish, paving the way for future research on viral persistence and inactivation strategies in this foodstuff.

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PubMed2026

Systematic review of machine learning approaches for predicting sickle cell crisis and mortality risk at the climate-health nexus.

BACKGROUND: Sickle cell anemia (SCA) is a severe genetic blood disorder characterized by recurrent vaso-occlusive crises and increased mortality, with the greatest burden occurring in low- and middle-income countries. Climatic and environmental conditions, including temperature variability, humidity, rainfall, air pollution, and seasonal changes, have been associated with disease exacerbation. However, the extent to which these factors have been incorporated into predictive models remains unclear. This study systematically reviews the application of machine learning (ML) models for predicting SCA crises and mortality in relation to climate and environmental factors. METHODOLOGY: The PRISMA guidelines were used, and 34 peer-reviewed studies published between 2005 and 2026 were analyzed to identify the climate variables, ML approaches employed, and predictive performance. The reviewed studies applied a range of ML techniques, including artificial neural networks, random forests, support vector machines, decision trees, logistic regression, and deep learning models. Temperature, humidity, rainfall, wind speed, air quality indicators, and seasonal patterns were the most frequently examined environmental variables. RESULTS: The findings indicate that most existing models rely predominantly on clinical and demographic data, with limited integration of climate information and inadequate representation of high-burden regions, especially Sub-Saharan Africa. Studies incorporating environmental variables reported improved predictive performance and highlighted the potential of climate-informed early warning systems for SCA management. CONCLUSION: The review recommends development of interdisciplinary, climate-aware ML frameworks, expansion of longitudinal environmental datasets, and increased research in underrepresented regions to support climate-resilient and patient-centered SCA care.

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PubMed2026

New Evidence in Heart Failure: 2026 Update.

Heart failure (HF) remains a major cause of morbidity, mortality, impaired quality of life and healthcare expenditure worldwide. The global burden of HF continues to increase due to population aging, improved survival, and the growing prevalence of cardiovascular, renal, and metabolic comorbidities. Simultaneously, the pace of scientific progress in HF has accelerated considerably. Recent advances have refined our understanding of HF epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery. The Second Universal Definition of HF has also updated the classification framework, moving beyond the traditional ejection fraction-based categories. HF is now broadly classified into two major phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Novel mechanistic insights highlight the role of inflammation, immune activation, metabolic dysfunction, mitochondrial biology, and multisystem interactions in HF progression. There has also been significant progress in the characterization and management of major comorbidities, including chronic kidney disease (CKD), diabetes, obesity, atrial fibrillation (AF), pulmonary hypertension, frailty, malnutrition, and cancer. Diagnostic innovations include novel biomarkers, multi-omics technologies, artificial intelligence-based approaches, advanced imaging techniques, congestion assessment tools, and emerging digital health solutions. Important advances have occurred in specific HF aetiologies, including cardiomyopathies, cardiac amyloidosis (CA), myocarditis, arrhythmia-induced cardiomyopathy (AiCM), and Chagas cardiomyopathy. Therapeutic developments continue to reshape HF management across the spectrum of left ventricular ejection fraction. Recent evidence has focused on optimization of guideline-directed medical therapy in HFrEF, expansion of evidence-based therapies in HFpEF, and growing roles for sodium-glucose cotransporter-2 inhibitors, finerenone, incretin-based therapies, and transcatheter valve interventions. Collectively, these advances support the transition from a predominantly phenotype-based approach towards a more personalized and biologically informed model of HF care, with the potential to further improve outcomes across the entire HF spectrum.

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PubMed2026

Aflatoxins and their biosynthetic precursors in lotus seeds: simultaneous UPLC-MS/MS determination, contamination profiling, and matrix-specific accumulation during Aspergillus flavus infection.

Aflatoxin (AF) contamination poses a severe global threat to food and medicinal material safety, yet existing research focuses on terminal AF metabolites while neglecting residual biosynthetic precursors, leading to potential underestimation of contamination risks. In this study, a UPLC-MS/MS method was established for the simultaneous quantification of six AFs and their five precursors in lotus seeds, with optimization of mass spectrum parameters, chromatographic separation conditions, and sample pretreatment. Method validation confirmed linearity (R2 > 0.99), LODs (0.03-0.36 μg/kg), and recoveries (76.53%-120.0%, RSD < 15%). Analysis of 41 natural lotus seed samples revealed a 63.4% AF contamination rate, dominated by B-group AFs, while O-methylsterigmatocystin (OMST) and versicolorin hemiacetal (VOH) were identified as the primary co-residual precursors with co-occurrence rates ≥ 50%. Notably, AFM1 was predominantly detected in natural samples with AFB1 concentrations exceeding 100 μg/kg. Artificial inoculation experiments further demonstrated that sterilization and sealing conditions modulated AF biosynthesis in lotus seeds, with non-sterilized and non-sealed groups showing delayed fungal metabolism and lower toxin accumulation. A significant linear correlation was observed between AFM1 and AFB1 levels (r = 0.94) in infected samples, demonstrating their accumulation levels are coupled with fungal overall metabolic flux. Given the high co-occurrence rate of OMST/VOH with AFB1 in natural samples, their individual and combined toxicities require in-depth investigation. This work deciphers matrix-specific AF dynamics in lotus seeds, supporting regulatory standard refinement (e.g., precursor inclusion) and targeted control (e.g., time-sensitive drying after harvest). Further studies will focus on exploring the molecular mechanisms of substrate-dependent AF synthesis.

Aflatoxins↗

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.

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PubMed2026

A narrative review of what cohorts have taught us and how they have laid the foundation for much of our understanding of type 2 diabetes.

This narrative review provides a historical perspective on how observational research on type 2 diabetes has been developed and consolidated over the last 50 years and how well-designed cohort studies will provide us with knowledge for research and practice in the future and aid guideline development. We have included data from a large number of cohorts from every continent that have been used to study the development and/or progression of type 2 diabetes, including cohorts that are general population-based, disease-based, intervention-based and registry-based. We have structured the results from the past 50 years based on the following themes: diagnosis and screening, complications, risk factors and pathophysiology. We also discuss the strengths and weaknesses of observational research when compared with other research designs. Finally, we discuss the emerging and future directions for type 2 diabetes research using cohorts, which include novel developments, such as artificial intelligence, precision health and the exposome. We conclude that cohort research has significantly advanced our understanding of type 2 diabetes and aided guideline development, and complements experimental work, such as human randomised controlled trials and animal studies. Both approaches are essential and complementary in our pursuit to provide a more comprehensive understanding of the development and progression of type 2 diabetes, and to change dogma, practice and policies for better outcomes.

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PubMed2026

Future promise, current clinical ambiguity: a systematic review of machine learning algorithm outputs predicting risk of cardiovascular disease.

OBJECTIVE: To examine whether the outputs of machine learning algorithms designed to predict risk of cardiovascular disease (CVD) address known deficiencies of the Framingham Risk Score (FRS) and improve risk estimates. METHODS: For this critical review, Medline, Embase and IEEE were searched from inception to 1 January 2025. Included were studies describing machine learning algorithms designed to specifically compare output of cardiovascular risk assessment with the FRS. Commentaries, letters, unpublished work or non-peer-reviewed papers were excluded.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two reviewers screened titles and abstracts independently, then populated a purpose-built data extraction form. A subsequent qualitative thematic analysis focused on algorithms' strengths, added value, potential harms, unintended consequences and equity implications.The main outcome assessed was whether, among healthy adults, the algorithm improved CVD risk prediction relative to the FRS. RESULTS: Of 707 studies retrieved, 29 met inclusion criteria. 23 reported improved predictive ability relative to the FRS. Most datasets and/or medical records used included sociodemographic predictors of CVD not included among FRS inputs. Some added costly diagnostic tests like CT angiography to FRS screening indicators. When they were defined, inputs and outcomes such as hypertension or myocardial infarction did not always adhere to FRS values. Statistical significance was generally taken as a proxy for clinical significance. Some algorithms overestimated the number at risk compared with the FRS without discussing whether that larger proportion might be at risk of overdiagnosis rather than CVD, while a few decreased the proportion found to be at risk. CONCLUSIONS: Use of artificial intelligence to improve accuracy of risk assessment for CVD demonstrates the technological capacity to merge known sociodemographic predictors with biologic variables and examine non-linear interactions among these. Still needed to achieve patient benefit is clinical insight, adherence to screening principles and cost-benefit assessment of inputs selected.

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PubMed2026

[Tafluprost/timolol fixed-dose combination versus tafluprost monotherapy for open-angle glaucoma and ocular hypertension: a multicenter, randomized, double-blind, parallel-group trial].

Objective: To evaluate the efficacy and safety of a preservative-free tafluprost/timolol maleate fixed-dose combination compared with preservative-free tafluprost monotherapy in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: This was a multicenter, randomized, double-blind, parallel-controlled clinical trial conducted across 25 centers, including the Eye & ENT Hospital of Fudan University, from January 2019 to November 2022. Patients diagnosed with OAG or OHT who required enhanced intraocular pressure (IOP) reduction after a 4-week washout period were enrolled. Participants were randomized 1∶1 to receive either tafluprost/timolol or tafluprost once daily for 3 months. The primary endpoint was the change from baseline in mean diurnal IOP (the average of measurements at 8:00, 10:00, and 16:00) at Month 3. Secondary endpoints included IOP changes at individual time points and the proportion of responders achieving predefined IOP reduction thresholds. Safety was assessed via the incidence of adverse events (AEs). Analysis of covariance (ANCOVA) using the Markov Chain Monte Carlo (MCMC) method was employed for the primary endpoint; superiority was established if the upper limit of the 95% confidence interval (CI) was<0 mmHg (1 mmHg=0.133 kPa). Continuous variables in secondary endpoints were compared using ANCOVA, and responder rates were analyzed using Fisher's exact test. Results: A total of 219 patients were enrolled (tafluprost/timolol group: n=110; tafluprost group: n=109). The primary efficacy analysis set included 215 patients (tafluprost/timolol: n=107; tafluprost: n=108). Baseline characteristics were well-balanced between the two groups. The majority of patients were male [127 (59.1%)] with a mean age of (44.80±15.71) years at screening. At Month 3, the mean diurnal IOP reduction from baseline was (6.56±3.44) mmHg in the tafluprost/timolol group and (5.36±2.94) mmHg in the tafluprost group. After adjusting for baseline IOP, the between-group difference was -1.312 mmHg (95%CI: -2.010 to -0.696); as the upper limit was<0 mmHg, tafluprost/timolol demonstrated superior IOP-lowering efficacy to tafluprost. Responder rates for IOP reductions of≥15%,≥25%, and≥30% were significantly higher in the tafluprost/timolol group (P=0.016, 0.028, and 0.032, respectively). The incidence of ocular AEs was 20.0% (22/110) in the tafluprost/timolol group and 26.6% (29/109) in the tafluprost group. The most common AE was conjunctival hyperemia, occurring in 2.7% (3/110) and 8.3% (9/109) of the groups, respectively. Conclusion: Compared with preservative-free tafluprost monotherapy, the tafluprost/timolol combination provides significantly greater IOP reduction in patients with OAG and OHT, while maintaining a favorable safety profile.

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PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

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PubMed2025

The wider erection angle in hypospadias: A neglected feature affecting surgical outcomes.

INTRODUCTION: Penile curvature often accompanies hypospadias, and numerous techniques have been described for its correction; however, in some cases, an abnormal erection angle may also be present, further exacerbating the perception of curvature. OBJECTIVE: This study investigates the significance of the erection angle in hypospadias cases and its correlation with the severity of the anomaly. STUDY DESIGN: A retrospective analysis of intraoperative photographs of hypospadias cases operated between 2019 and 2023 was performed. Erection angle was measured with a digital goniometer during a full artificial erection. Erection angles in proximal and distal hypospadias cases were analyzed and compared to data from Kinsey's subgroups representing healthy male erection angles. RESULTS: This study involved images of 68 patients, with 31 having proximal and 37 distal hypospadias. The median age of the whole group was 11 months (6-156, IQR 9). Median erection angle was 91 (63-119, IQR 11) for distal cases, whereas it was 96 (75-138, IQR 21) for proximal cases. The difference was statistically significant (p = 0.009). The erection angle distribution in our cohort, including both proximal and distal hypospadias cases, skewed toward wider angles, highlighting a distinct pattern compared to data constituted by Kinsey and Sparling. DISCUSSION: Our findings indicate that the erection angle in hypospadias is significantly wider in proximal cases, suggesting a correlation between erection angle and severity of the hypospadias. While we acknowledge the limitation of comparing our prepubertal cohort with Kinsey's adult data, the absence of evidence suggesting significant post-pubertal changes in erection angle justifies this approach. Additionally, the use of digital images for angle assessment is not a standardized technique in hypospadias evaluation; these images were initially captured for curvature assessment. Despite these limitations, our study provides novel insights into seldom mentioned association with hypospadias - a wide erection angle, emphasizing the need for further research on its implications for surgical planning and long-term outcomes. CONCLUSION: This study introduces a wider erection angle as an additional characteristic of hypospadias particularly pronounced in proximal cases. To our knowledge, this is the first focused investigation on addressing this aspect of the condition. It emphasizes the need for further research on adults with wide post-repair erection angles to explore its long-term impact on sexual function and aesthetics.

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PubMed2026

Suppression of HIV-1 replication in CEM-A cell cultures by trans-splicing group I introns targeting PAS/PBS sequences and conditionally expressing ΔN-Bax.

Anti-HIV group I introns containing antisense guide sequences directed against the HIV-1 primer activation signal and primer-binding site (PAS/PBS) were designed and evaluated. Because PAS/PBS sequences are present in the viral RNA species examined, these RNAs can serve as trans-splicing substrates. The introns were active against both artificial target RNAs and viral RNA generated during infection. Cleavage and degradation of targeted viral RNA may have contributed to suppression, whereas inclusion of a 3' exon encoding the proapoptotic protein ΔN-Bax was associated with increased programmed cell death and may have augmented suppression of viral replication. In cultured CEM-A cells, transgene expression of these introns markedly suppressed HIV-1 replication, with p24 levels falling below the assay detection limit in selected clones. RESULTS: RT-PCR and sequence analysis detected splice products containing the expected PAS/PBS junctions. In the dual-luciferase assay, intron expression reduced normalized Gaussia luciferase signal by approximately 70% relative to the negative control. Qualitative Annexin V imaging and caspase-3 assays were consistent with infection-dependent apoptosis after ΔN-Bax splice-product formation. Transient expression of each intron in HEK293T cells followed by infection with VSV-G-pseudotyped HIV-1NL4-3 at an MOI of 2 reduced p24 levels by approximately 50% at 4 days post-infection. Construct 128L produced the strongest RT-PCR band under the tested conditions and was selected for subsequent experiments. A canonical splice product and a low-abundance noncanonical splice product were detected; both involved the intended HIV-derived target RNA, although transcriptome-wide off-target splicing was not assessed. Heterogeneous transformed HEK293T populations showed an approximately 2-log10 reduction in p24. In selected clonal HEK293T and CEM-A lines, p24 was below the assay detection limit at the measured endpoints, including up to 90 days after infection in some CEM-A clones. CONCLUSIONS: PAS/PBS-targeting group I introns suppressed HIV-1-associated p24 production in the tested cell-culture models. Linking the introns to a ΔN-Bax 3' exon was associated with infection-dependent apoptosis and may further limit viral replication and spread. The use of highly conserved, functionally constrained target sequences may reduce the likelihood of escape, but viral evolution and transcriptome-wide off-target effects were not assessed. This conditional death-upon-infection strategy warrants further evaluation in primary-cell and in vivo models.

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