• Prevalence and determinants of drug-resistant pulmonary tuberculosis in the MENA region: a systematic review and meta-analysis.
    2 weeks ago
    Multidrug-resistant tuberculosis (MDR-TB) is a constraining challenge for tuberculosis (TB) control worldwide. The Middle East and North African (MENA) region represents a significant part of the global MDR-TB burden.

    To estimate the pooled prevalence of MDR-TB and its determinants in the MENA region.

    We searched for studies published in English and French on the subject up to 31 January 2026 on Web of Science, PubMed, Scopus and Cochrane, without time restriction. Original studies reporting data on the prevalence of MDR-TB in individuals living in the MENA region were selected. The meta-analysis was done using the random effects model considering the heterogeneity among the included studies and I 2 statistic was used to assess the heterogeneity.

    A total of 1239 articles were identified and 25 studies from 6 countries were included in this review. The prevalence of MDR-TB in the MENA region ranged from 0% (95% CI 0% to 4.1%) to 17.1% (95% CI 10.6% to 25.4%). The pooled prevalence was 3.54% (95% CI 2.18% to 5.72%) with a high heterogeneity, I2 =95.6%; 95% CI 94.4% to 96.5%. Previous exposition to TB treatment, HIV infection, smoking and the presence of comorbidities were the most reported associated factors.

    This review underscores the persistence of MDR-TB in the MENA region, suggesting insufficiency in TB control. Multisectoral interventions integrating strong prevention measures, standardised treatment protocols and measures to enhance treatment adherence should be implemented.
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  • Management of extensive surgical emphysema with subcutaneous drain and incisional negative pressure wound therapy.
    2 weeks ago
    This report details a man in his late 60s who presented with a new right-sided pneumothorax against the background of advanced COPD and a known large apical bulla. Multiple chest drains were inserted to manage the pneumothorax but the patient developed extensive surgical emphysema causing significant distress. Reported here is the management of the extensive surgical emphysema and techniques used to insert a subcutaneous drain and incisional negative pressure wound therapy, ultimately with positive results. This report will briefly explore other techniques to manage subcutaneous emphysema, with the focus then on how negative pressure wound therapy can be implemented and benefit patients who are too frail/comorbid for further invasive interventions.
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  • Machine Learning-Based Multidimensional Oximetry for Obstructive Sleep Apnea Screening: Development and External Validation.
    2 weeks ago
    Obstructive sleep apnea (OSA) affects nearly one billion people globally and poses a substantial public health threat. Effective and accessible methods for OSA risk identification are urgently needed.

    This study aims to develop and externally validate a machine learning model derived from multi-parameter pulse oximetry (SpO2) for OSA screening, and to evaluate its performance, interpretability, and robustness across sex and age subgroups.

    Of 4156 screened participants, 2195 underwent polysomnography (internal cohort) and 446 received home sleep apnea testing (external cohort). Eight SpO2-derived parameters, including oxygen desaturation index (ODI), hypoxic burden (HB), and ST90 (percentage of sleep time with SpO2 < 90%), were used to construct models. Six machine learning algorithms were trained, with F1-score as the primary metric and area under the curve as the secondary metric. Model interpretability was assessed using Shapley additive explanations and intrinsic feature importance scores.

    Nonlinear parameter-risk relationships were observed between oximetry indices and OSA probability. The 4-parameter ODI-HB-MinSpO2-ST90 model achieved optimal performance (F1-score = 0.9516, area under the curve = 0.9879), surpassing all single-parameter models. Shapley additive explanations analysis identified ODI, HB, and MinSpO2 as key predictors. The ODI-HB-MinSpO2-MeanSpO2 configuration demonstrated superior performance in female and younger subgroups, whereas the ODI-HB-MinSpO2-ST90 model remained optimal for male and older participants. Categorical boosting outperformed other algorithms across multiple metrics and remained robust in both subgroup and external validation analyses.

    The multi-parameter oximetry model based on the categorical boosting algorithm provides a simple and accurate tool for OSA screening. Sex- and age-stratified strategies can further enhance its clinical applicability.
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  • Life lost due to the COVID-19 pandemic: A model-based cohort analysis of mortality displacement in the registered population of England.
    2 weeks ago
    Uncertainty about the prior health status of those dying during the pandemic has fuelled debate about its impact. To date, attempts to quantify life years lost during the pandemic have relied on using life tables without taking into account varying levels of vulnerability among those that died.

    Using retrospective, linked data from March 2020 to September 2022 for the cohort of all individuals in England alive at outset, we quantified the risk of death, associated with a wide variety of comorbidities, using primary care and hospital data, as well as evidence of vaccination and COVID-19 infection. We then simulated the survival of every individual in the population with a positive COVID-19 test, with and without the assumption that COVID-19 affected their survival, taking account of their personal vulnerability. We used the difference between these simulated survival times to estimate mortality displacement (how long those who died would have lived, had they not tested positive). We used the displacement estimates for those aged 65 and older to revise estimates of excess deaths.

    We estimated median mortality displacement of 4.8 (IQR = 1.5 to 16) years for females and 4.4 (IQR = 1.4 to 12.6) years for males at ages 65 and over. We estimate 28% of those dying with COVID-19 aged 65 and over would have survived five years or more without the infection (66% for females aged 65-74).

    Life expectancy of those who died with COVID-19 was substantial and, based on our analysis of vulnerability, most of those who died at ages 65 and over are unlikely to have been close to death. In future pandemics, real-time modelling of displacement would be helpful in assessing the mortality impact of the pandemic.
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  • Differences in the long-term course of post-COVID-19 symptoms in adults and children across epidemic periods: A retrospective cohort study in Japan, 2020-2024.
    2 weeks ago
    The prevalence of post-COVID-19 symptoms has been reported to decline since the Omicron variant became predominant. However, differences in their long-term course across epidemic periods and between adults and children, including recent Omicron sublineages, remain insufficiently understood.

    We extended a previously reported retrospective cohort by conducting follow-up and an additional survey in Hiroshima, Japan. The study included 2,689 individuals diagnosed with COVID-19 between March 2020 and June 2024 (1,524 adults and 1,165 children). A self-administered questionnaire captured the presence and duration of 13 symptoms. Interval-censored survival analysis estimated prevalence over time, and proportional hazards models evaluated factors associated with symptom resolution.

    At six months, the estimated prevalence in adults was highest during the Delta period (47%) and lower during Omicron-2022 (23%) and Omicron-2024 (21%). In children, prevalence remained about one-quarter to one-third that of adults, with no notable differences between Omicron sublineages. At two years, persistent symptoms were reported by about 20% of adults infected before Omicron and 10% during Omicron periods, compared with 4.1% and 1.9% of children infected during the Delta and Omicron-2022 periods. Symptoms persisting beyond two years showed little further resolution, though in children they did not interfere with daily activities. In the Cox model, resolution was slower during the Delta period (HR 0.79) and faster during Omicron-2022 (HR 1.24) and Omicron-2024 (HR 1.30). Younger age, particularly ≤12 years, was strongly associated with faster recovery.

    The long-term course of post-COVID-19 symptoms differed across epidemic periods and age groups. The risk was highest during Delta and lower among children and those infected during Omicron waves, yet some individuals experienced symptoms for over two years. Long-term follow-up and social support remain crucial to mitigate the burden of post-COVID-19 condition.
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  • Effect of screen time and outdoor activities on myopia progression.
    2 weeks ago
    To assess the impact of screen time and outdoor activities on myopia progression in Lebanese children and to compare age groups.

    This prospective study enrolled 100 myopic children aged 3-17 years who presented to the pediatric ophthalmology service at the American University of Beirut Medical Center from February 2023 to January 2025. Behavioral data were obtained using a questionnaire, and clinical data were collected through retrospective chart review dating back to January 2018. Myopia was defined as a spherical equivalent (SE) ≤ -0.50 diopters (D). Annual myopia progression was compared during and after the COVID-19 lockdown and correlated with screen time and outdoor activity.

    The mean age was 13.2 ± 3.6 years, with a balanced sex distribution. Myopic progression was significantly higher during the COVID-19 lockdown, with the highest progression in 2020-2021 (0.65 ± 0.07 D/year) compared with 2022-2023 and 2023-2024 (both 0.29 ± 0.05 D/year; p < 0.001). Mean SE became more negative over time, reaching -3.43 ± 0.23 D in 2024 (overall p < 0.001). During lockdown, screen time increased significantly (p < 0.001), while outdoor activity decreased significantly (p < 0.001). Twenty-two percent had more than 8 hours of daily screen exposure. Outdoor activity varied: 38% spent 5-10 hours outdoors weekly and 20% exceeded 10 hours. Younger children preferred tablets (p < 0.001) and spent less time on screens (p < 0.001). Nevertheless, questionnaire-derived daily screen time, weekly outdoor time, and screen‑break variables were not statistically significantly associated with myopia progression during or after the lockdown periods in the overall cohort (all p > 0.05).

    Myopia progression rate was higher during the COVID-19 lockdown than in the post-lockdown period, with significantly higher progression rates in 2020-2021 compared with 2022-2023 and 2023-2024. Screen time increased and outdoor time decreased during lockdown, but were not statistically significantly associated with progression in the overall cohort. These findings add evidence from an underrepresented Middle Eastern population, supporting further longitudinal studies of modifiable environmental factors in myopia progression.
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  • Viral-bacterial codetection and clinical and laboratory characteristics in children hospitalized with lower respiratory tract infections in a private hospital in Lima, Peru: a cross-sectional study.
    2 weeks ago
    Viral-bacterial codetection is common and may increase clinical severity, but evidence in the Peruvian pediatric population is limited. The objective of the present study was to evaluate the clinical, laboratory, and seasonal characteristics associated with viral-bacterial codetection in children hospitalized for lower respiratory tract infections (LRTIs).

    Cross-sectional secondary database study from a private hospital in Lima, Peru. We included patients < 13 years hospitalized for LRTIs with RT-qPCR results for respiratory viruses and/or bacteria. Viral-bacterial codetection was compared against other detection patterns using Poisson regression for binary outcomes and linear regression for continuous outcomes, with false discovery rate (FDR) correction for multiple comparisons.

    A total of 548 patients were included (median age 2.0 years; 50.5% female). Viral-bacterial codetection was identified in 21.5% of patients (n = 118), with RSV + Haemophilus influenzae being the most frequent combination. Compared with other detection patterns, viral-bacterial codetection was significantly associated with a higher prevalence of crackles (aPR: 1.30; 95% CI: 1.08-1.57), lower oxygen saturation at admission (β: -0.57; 95% CI: -1.04 to - 0.10), higher platelet counts (β: 30,452; 95% CI: 5,113-55,792), higher hemoglobin levels (β: 0.29 g/dL; 95% CI: 0.03-0.56), and longer hospital stay (β: 0.66 days; 95% CI: 0.02-1.29). However, after FDR correction for multiple comparisons, none of these associations reached statistical significance (q-values: 0.056-0.113). No difference was detected according to seasonality.

    Viral-bacterial codetection was common and was associated with crackles, lower oxygen saturation, longer hospital stay, and higher platelet counts; however, after FDR correction, none of these associations remained statistically significant, underscoring the exploratory nature of these findings and the need for larger, confirmatory studies.
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  • The ISG Atlas: a loss-of-function analysis characterizes antiviral properties of interferon stimulated genes.
    2 weeks ago
    The innate immune system requires the activity of interferon-stimulated genes (ISGs) to mount its protective response against viruses. However, the activity of ISGs against viruses varies widely and is orchestrated by the interplay of hundreds of ISGs. Utilizing a time-resolved, arrayed loss-of-function screen, we systematically investigate 285 ISGs for their virus-modulating activity against eight viruses. The quantitated data from the screen results do not necessarily result in similar quantitative biological effects of gene function but indicates virus specificity of many ISGs and pan-proviral activity of some ISGs, such as RNA 2',3'-cyclic phosphate and 5'-OH ligase (RTCB). Co-depletions of selected candidates identify ISGs with synergistic functions, highlighting particularly strong synergies between ISGs inhibiting entry pathways and ISGs involved in IFN signaling. Among unexplored ISGs, we identify BORCS8, which has a particularly prominent role in modulating SARS-CoV-2 infection. Mechanistically, BORCS8 mediates the acidification of early endosomes during viral entry, a process known to facilitate the degradation of virus particles. Collectively, this extensive resource reveals specificities of ISGs identified in this screening system and suggests potential strategies for antiviral treatment options.
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  • Persistence of alveolar fibroblast-derived ADAMTS4+ cells in a preclinical model of delayed pulmonary fibrosis resolution.
    2 weeks ago
    Idiopathic pulmonary fibrosis is the most common and aggressive form of interstitial lung disease. Despite extensive research on the pathomechanisms of fibrogenesis, little is known about the mechanisms of fibrosis resolution. Here, lineage tracing of alveolar fibroblasts was carried out during fibrosis development and delayed resolution in aged mice. Histological analyses, single-cell transcriptomics, and ex vivo models including alveolar organoids and precision-cut lung slice cultures were employed. The data reveal that lipofibroblasts contribute to myofibroblast formation during fibrogenesis, with the reverse differentiation trajectory occurring during fibrosis resolution. Importantly, delayed resolution is associated with the persistence of ADAM metallopeptidase with thrombospondin type 1 motif 4-positive (ADAMTS4+) cells. Investigation of human lung transplant tissues, single-cell and spatial transcriptomic datasets, and functional ex vivo interventions reveal strong clinical relevance. Our study underscores the significance of the lipofibroblast-to-myofibroblast reversible switch in fibrosis development and resolution and identifies ADAM metallopeptidase with thrombospondin type 1 motif 4 as a potential therapeutic target in human lung fibrosis.
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