• Pathogen prevalence, feature composition and cross-centre generalisability of machine learning diagnostic models for multi-pathogen respiratory infection.
    1 week ago
    To evaluate the predictive information contained in the restricted surveillance feature set (demographic, temporal and specimen variables) for respiratory pathogen identification, and to examine factors associated with model performance.

    We retrospectively analysed 24,689 acute respiratory infection cases from seven sentinel hospitals in Sichuan, China; after quality control, 21,395 samples with complete 21-pathogen testing were included. Per-pathogen multi-label binary classifiers were trained using 15 features available at presentation; logistic regression, random forest, back-propagation neural network and XGBoost were compared under an identical split and threshold-selection protocol, with thresholds derived from out-of-fold probabilities. Label-definition sensitivity, leave-one-hospital-out cross-validation and prevalence-performance association were analysed.

    Random forest and XGBoost performed comparably (XGBoost the primary model), with Macro-F1 0.1553 (95% CI 0.104-0.2091), 0.2202 for common pathogens and Macro-AUC 0.7702; the four-algorithm spread was 0.0611. Log-prevalence correlated strongly with per-pathogen F1 (r = 0.851); the seven rare pathogens reached Macro-F1 0.0255. Leave-one-hospital-out validation gave Macro-F1 0.1073 ± 0.0289 (-30.9%) and Macro-AUC 0.6841 (-11.2%). Feature ablation showed temporal and non-temporal features were largely redundant (Macro-F1 0.1153 vs. 0.1147; AUC 0.6892/0.6865 vs. 0.7702). Treating untested as negative lowered Macro-AUC to 0.7653, whereas simulated false-negative label contamination had minimal effect.

    Models built on the restricted surveillance feature set showed limited diagnostic performance and were not demonstrated suitable for clinical deployment. Performance was strongly associated with pathogen prevalence and constrained by limited feature informativeness, while algorithm choice contributed little and cross-centre generalisability was limited. Priorities include multimodal feature integration, rare-pathogen accrual and prospective multicentre external validation.
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  • FreeSurfer-based amygdala subfield volumetry in long COVID and ME/CFS: clinical and immunological correlations.
    1 week ago
    Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) share debilitating symptoms and have been associated with limbic-system dysfunction. We investigated amygdala subfield volumes to identify disease-specific neuroanatomical features and their clinical and immunological correlates.

    We prospectively examined 27 patients with long COVID, 38 patients with ME/CFS, and 47 healthy controls (HCs). Amygdala subfields were segmented using high-resolution 3-T MRI and FreeSurfer software. Group comparisons were performed using analysis of covariance, and partial correlations with clinical and immunological indices, including autoantibodies, plasmablasts, regulatory T cells (Tregs), and Eomesodermin-positive helper T cells (Eomes+ Th cells), were assessed.

    Patients with long COVID had nominally larger right cortical nucleus volumes than HCs (raw p = 0.040; Bonferroni-adjusted p = 0.119), whereas patients with ME/CFS had a nominally larger left paralaminar nucleus (raw p = 0.048; Bonferroni-adjusted p = 0.145). In long COVID, G-protein-coupled receptor (GPCR) autoantibodies were nominally negatively associated with right medial nucleus volume. In ME/CFS, performance status was nominally positively associated with the right basal nucleus, right paralaminar nucleus, and right whole amygdala, and plasmablasts were nominally positively associated with the right corticoamygdaloid transition area. No group difference or partial correlation remained significant after correction for multiple testing.

    Although no finding survived correction for multiple testing, the exploratory results suggest that amygdala-related structural variation may be relevant to both long COVID and ME/CFS. The nominal, uncorrected within-group patterns centered on olfactory-related amygdala nuclei and GPCR autoantibodies in long COVID, and on amygdala structure, functional severity, and plasmablasts in ME/CFS; however, these patterns do not support a conclusion of between-group differences. These observations are hypothesis-generating and do not establish disease-specific mechanisms. Prespecified validation in larger longitudinal and independent cohorts is required.
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  • Identification of clinical phenotypes and development of a predictive model for rapid lung function decline in COPD patients.
    1 week ago
    Chronic obstructive pulmonary disease (COPD) exhibits significant clinical heterogeneity. This study integrates phenotype identification with longitudinal lung function analysis to develop a prediction tool for rapid decline in a large Chinese cohort.

    This study included 38,863 COPD patients from a national multicenter screening program. Latent class analysis identified clinical phenotypes. Among 1,215 patients with baseline and 24-month follow-up spirometry, rapid decline was defined as annual FEV1 decline ≥40 mL or FEV1% predicted decline >1.5%. LASSO regression and the Boruta algorithm selected predictive variables. Six machine learning models were constructed and evaluated for discrimination, calibration, and utility. SHAP analysis was employed for interpretation.

    Three distinct phenotypes were identified: Phenotype 1 (GOLD Stage 2, non-smoking females, 25.8%), Phenotype 2 (GOLD Stage 1, smoking males, 44.8%), and Phenotype 3 (GOLD Stage 3, severe smokers, 29.4%). Phenotype 2 exhibited the highest rapid decline rate (55.8%). The CatBoost model achieved optimal performance (AUC 0.712) using six variables: region, fuel type, income level, wheezing, hip circumference, and baseline FEV1. SHAP identified baseline FEV1 as the top predictor. At a threshold of 0.365, the model attained 95.5% sensitivity and 86.4% negative predictive value, with significant net benefit.

    Three clinical phenotypes were identified among COPD patients. Phenotype 2 exhibits the highest risk of rapid progression, representing a key target group for intervention. The predictive model, based on six simple indicators, serves as a valuable tool for screening high-risk rapid decliners.
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  • Safety of a 4-Week Pediatric Home Mechanical Ventilated Pathway-A Single Center's Retrospective Study.
    1 week ago
    Pediatric Home Mechanical Ventilator (HMV) Programs have supported children with chronic respiratory failure since the 1970s, yet optimal caregiver training duration remains unclear. This study evaluated the safety and effectiveness of a standardized 4-week HMV multidisciplinary action plan (HMV MAP) by analyzing hospital length of stay (LOS) and 30-day revisit rates.

    A retrospective cohort study was conducted at a single center, including 59 children (ages 0-21) with tracheostomy and chronic home ventilator use who completed the HMV MAP training between 2016 and 2021. Data were extracted from electronic medical records. Existing home ventilator-dependent patients re-admitted for any reason, HMV MAP patients on palliative, hospice and/or concurrent care for home, as well as patients discharged to long-term care facilities/subacute care facilities were excluded.

    Of 59 eligible patients, the most common indication for long-term mechanical ventilation was chronic respiratory failure due to respiratory insufficiency. The HMV MAP median LOS was 37 days (IQR: 12-92). There were 30 patients who had extended LOS (eLOS HMV MAP). Of these, 21 were due to non-respiratory causes, with 14 being medical-related and 7 being social-related. Among patients discharged in 4 weeks, 0% had ED visits within 48 h of discharge, 17% were readmitted within 30 days for respiratory complications and 6.9% for non-respiratory complications; compared to 6.7%, 10% and 10% respectively for eLOS 4 W HMV MAP.

    The HMV MAP appears safe and effective, with low early ED visits and readmission rates. Most discharge delays were due to non-respiratory factors, suggesting the pathway may benefit from flexibility to accommodate medical and social complexities.
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  • Postoperative Respiratory Events and Risk Factors After Hip Reconstruction in Children With Neurological Complex Chronic Conditions.
    1 week ago
    Children with neurological complex chronic conditions (NCCCs) frequently undergo hip reconstruction for hip displacement. Impaired airway clearance and respiratory muscle weakness may increase the risk of postoperative respiratory events. This study evaluated the incidence and predictors of postoperative respiratory events in this population.

    We retrospectively reviewed children with NCCCs who underwent hip reconstruction between 2015 and 2024. Baseline characteristics included age, sex, diagnosis, comorbidities, feeding method, ambulatory status, and respiratory support. Operative and anesthesia-related variables included the number of osteotomies, operative duration and scheduling, estimated blood loss, airway device, and arterial blood gas measurements. The primary outcome was postoperative desaturation (SpO2 < 95%) requiring supplemental oxygen. Secondary outcomes included pulmonary complications and intensive care unit (ICU) utilization. Predictors were initially evaluated using an expanded multivariable logistic regression model, followed by a reduced model using Firth's penalized logistic regression.

    Among 126 children (mean age, 7.7 ± 4.1 years), postoperative desaturation occurred in 30 (23.8%). Pulmonary complications included respiratory failure (n = 6), atelectasis (n = 5), pulmonary edema (n = 3), and pneumonia (n = 1). ICU care was required for 22 children (17.5%). Predictors of postoperative desaturation included congenital brain malformation (adjusted odds ratio [aOR], 21.76; 95% confidence interval [CI], 3.33-249.48), surgery performed on Friday (aOR, 3.35; 95% CI, 1.11-10.24), ≥ 3 osteotomies (aOR, 7.82; 95% CI, 1.83-36.36), and elevated intraoperative bicarbonate (HCO3 - > 26 mEq/L; aOR, 6.49; 95% CI, 2.36-19.14).

    Postoperative desaturation was common after hip reconstruction in children with NCCCs, with a subset developing pulmonary complications or requiring ICU care. Identification of perioperative risk factors may improve risk stratification and support targeted respiratory monitoring and preventive strategies in this high-risk population.

    Level III, retrospective cohort study.
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  • Streptavidin-Displaying E. coli Scaffolds Enable Target-Mediated Gold Nanoparticle Assembly for Colorimetric Biosensing.
    1 week ago
    Enhancing the visual detection sensitivity of point-of-care (POC) optical sensors without resorting to complex, multistep chemical or enzymatic signal amplification remains a major challenge in sensor nanotechnology. Here, we present a multifunctional bio-nanostructured hybrid platform that integrates engineered Escherichia coli cellular scaffolds with antibody-functionalized gold nanoparticles (AuNPs) for high-sensitivity, solution-phase colorimetric sensing. By exploiting the biotin-streptavidin interaction through the Lpp-OmpA outer-membrane display system, the engineered bacterial cells serve as high-capacity, multivalent biological interfaces with a large effective surface area and high recognition-site density. Using SARS-CoV-2 nucleocapsid protein as a model biomarker, target-mediated bridging between AuNP-antibody probes and bacterial scaffolds promotes localized AuNP assembly and enhanced plasmonic coupling, resulting in a distinct visual color change within 30 min. The optimized assay achieved a naked-eye limit of detection (LOD) of 10-12 mol, representing a 10-fold sensitivity enhancement over conventional scaffold-free AuNP assays. This study provides a proof of concept for leveraging engineered living cells as multifunctional nanostructured templates. The modular, plug-and-play architecture of the biotin-streptavidin coupling interface highlights its potential for adaptation to clinical diagnostics and environmental monitoring.
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  • [Custom-made mandibular advancement devices for OSAS and snoring].
    1 week ago
    Obstructive sleep apnea syndrome (OSAS) remains widely underdiagnosed, despite its well-established cardiovascular and cognitive consequences. Although continuous positive airway pressure (CPAP) remains the first-line treatment for severe OSAS and for moderate OSAS associated with comorbidities, adherence often remains suboptimal. Custom-made mandibular advancement devices (MAD) therefore represent an attractive therapeutic alternative for patients with symptomatic mild to moderate OSAS. Generally better tolerated than CPAP, they are associated with better adherence. This article guides clinicians through the different stages of patient management with MAD : indication, fabrication and treatment follow-up.
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  • Tailoring Na+ and Cl--Selective Colorimetric Optode Arrays for Wearable Sweat Analysis: Composition Optimization and Measurement Conditions.
    1 week ago
    Sweat testing is central to cystic fibrosis diagnosis, but conventional analysis depends on clinical instrumentation, creating a need for portable point-of-care alternatives. As Part 1 of this two-part study, we systematically optimized Na+- and Cl--selective colorimetric optodes and their measurement protocols for potential integration into a wearable device for in situ sweat analysis. Fifteen chromoionophore-based sensor compositions were screened over the physiologically relevant range of 5-100 mmol/L. Candidate optodes were selected based on stability in NaCl solutions and artificial sweat, hysteresis below 0.1 log units, and equilibration times under 15 min. Their analytical performance was evaluated by spectrophotometry and digital color analysis using smartphones and research-grade cameras, with a robustness parameter used to quantify signal reliability under different imaging conditions. A simple smartphone setup provided more robust performance than the tested laboratory imaging configurations. Incorporating light-scattering TiO2 particles into the PVC matrix produced opaque films that significantly reduced interference from colored samples without compromising sensitivity or response kinetics. Validation in artificial sweat yielded recoveries above 93% across pH 5.5-8.0. These results establish optimized sensor compositions and measurement conditions for colorimetric Na+ and Cl- determination in sweat and provide the analytical basis for wearable-device development in Part 2.
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  • Sleep disorders in patients with HIV.
    1 week ago
    The improved survival of people with HIV (PWH) comes with increasing exposure to age-related, metabolic, neuropsychiatric, and cardiovascular risk factors that predispose them to sleep disorders and associated comorbidities. This narrative review examines the current burden, spectrum and causes of sleep disorders in PWH as well as current practice recommendations for their management.

    Insomnia and sleep apnea and hypopnea syndrome (SAHS) remain the most common sleep disorders in PWH. Although there is paucity of data on the prevalence of circadian rhythm abnormalities and parasomnias, in particular rapid eye movement (REM) sleep behavior disorder (RBD) in PWH, emerging evidence suggests that these disorders abound and deserve further attention regarding their burden, impact and implication for management in PWH. While cognitive behavioral therapy for insomnia (CBT-I) remains the first line management of Insomnia, updated recommendation by AASM allows for the use of CBT-I plus medication in individuals who desire increased sleep time early on in the condition. Continuous positive airway pressure (CPAP) and auto-adjusting PAP (APAP) are preferred modalities of treatment of obstructive sleep apnea. In the same vein, PAP therapies are recommended in patients with CSA. Refractory CSA might benefit from transvenous phrenic nerve stimulation. Gabapentinoids rather than dopamine agonists are now the first line treatment for restless leg syndrome (RLS). Recent recommendation for Iron supplementation lacks HIV specific modification hence, cautious clinical monitoring for Iron overload and symptomatic control of RLS in PWH is suggested.

    Current evidence supports the use of guideline-directed interventions. The implication of iron supplementation for RLS in this population deserves future trial.
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  • Factors associated with primary rifampicin-resistant/multidrug-resistant TB: a case-control study.
    1 week ago
    <sec><title>BACKGROUND</title>Multidrug-resistant TB (MDR-TB) threatens TB control in Bhutan. According to the 2017 national Drug Resistance Surveillance report of the Royal Centre for Disease Control, 13.7% of new pulmonary TB cases had rifampicin resistance, of whom 98% were also resistant to isoniazid. We investigated the factors associated with primary rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) among new pulmonary TB patients.</sec><sec><title>METHODS</title>We conducted a nationwide case-control study including 46 laboratory-confirmed primary RR/MDR-TB cases and 138 drug-susceptible pulmonary TB controls (1:3 ratio). Multivariable logistic regression identified factors independently associated with primary RR/MDR-TB.</sec><sec><title>RESULTS</title>Factors associated with primary RR/MDR-TB were delay in diagnosis (adjusted odds ratio [AOR] 24.9, P < 0.001), poor household ventilation (AOR 3.6, P = 0.023), contact with MDR-TB patients (AOR 7.2, P < 0.001), living alone (AOR 10.8, P = 0.016), perceived health staff unfriendliness (AOR 9.6, P = 0.004), and TB medicine unavailability (AOR 16.5, P = 0.024). Increasing age was associated with lower odds of RR/MDR-TB (AOR 0.94 per year, P = 0.005).</sec><sec><title>CONCLUSION</title>Primary RR/MDR-TB in Bhutan was strongly associated with delayed diagnosis, contact with known MDR-TB patients and modifiable health-system factors. Expanding rapid molecular testing, strengthening contact investigation, and improving patient-centred care are critical to interrupt transmission and sustain TB control gains.</sec>.
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