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.

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.

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.

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.

A 47-year-old woman with Parkinson disease (PD) complicated by severe motor fluctuations had been treated with deep brain stimulation (DBS) for 11 years and intestinal carbidopa/levodopa infusion for 5 years. Three months after her most recent clinic visit, at which both the DBS and infusion pump systems were confirmed to be functioning appropriately, she presented to the emergency department with abnormal movements. On examination, she had continuous, generalized, involuntary hyperkinetic movements with an erratic, dance-like quality, consistent with levodopa-associated dyskinesia. Evaluation revealed rhabdomyolysis, subcutaneous emphysema, and pneumomediastinum. She required admission to the intensive care unit for sedation and airway protection. After a key surgical intervention, she rapidly returned to her previous neurologic status and was discharged home. This case highlights the approach to acute dyskinesia and underscores the challenges of managing severe motor fluctuations in patients with PD.

H5Nx clade 2.3.4.4b viruses are evolving rapidly, expanding host ranges and threatening animal and public health. In the US, genotype B3.13 dominates dairy outbreaks, while D1.1 is linked to fewer cases. In the UK, an asymptomatic ewe infected with genotype DI.2 raised concerns about ruminant susceptibility. We inoculated lactating and nonlactating sheep with D1.1 (H5N1) and A6 (H5N5) viruses. Intramammary inoculation in lactating sheep caused clinical mastitis, high viral loads in milk, and transmission to suckling lambs, which further spread infection to the uninoculated mammary glands. Both ewes and their lambs seroconverted. Aerosol exposure of nonlactating sheep led to transient respiratory infection, with low-level viral replication, and seroconversion. In vitro, both viruses replicated in sheep mammary epithelial cells. These findings establish sheep as a viable ruminant model for H5N1 and H5N5 infection and highlight previously unidentified transmission dynamics, including milk-mediated and lamb-to-ewe spread, relevant for surveillance and biosecurity in ruminant populations.

Pleuroparenchymal fibroelastosis (PPFE) is a progressive interstitial lung disease (ILD) with defining histology of intra-alveolar fibrosis with septal elastosis (AFE), suggesting unique cellular disease processes. Here, we present a binational single-nucleus RNA sequencing atlas of PPFE, based on explanted lungs from 40 patients. Immunofluorescence microscopy, RNA in situ hybridization, micro-computed tomography (CT), and hierarchical phase-contrast (HiP) synchrotron CT provided spatial context. We identify PPFE-associated adventitial and elastofibrotic fibroblasts as key drivers of elastotic remodeling within an inflammatory microenvironment, maintained by immune cells forming tertiary lymphoid structures. Spatial mapping reveals an intriguing zonation of AFE, maintained by intercellular circuits between PPFE-associated cell types. Comparative analysis with idiopathic pulmonary fibrosis highlights CTHRC1+ fibrotic fibroblasts and aberrant basaloid cells as conserved profibrotic cellular machinery mediating collagen deposition across ILDs. This integrative atlas defines the cellular landscape of PPFE and dissects elastotic from fibrotic remodeling, providing a molecular rationale for niche-specific therapeutic strategies.

Primary ciliary dyskinesia (PCD) is a rare multi-system cilia-related disorder, and approximately 50% of individuals with PCD exhibit left-right asymmetry disorder. The dynein axonemal heavy chain 11 gene (DNAH11) pathogenic variants are responsible for primary ciliary dyskinesia 7, with or without left-right asymmetry disorder. This study aimed to detect the pathogenic variants in three unrelated patients diagnosed with PCD or left-right asymmetry disorder based on the clinical and imaging examinations. Whole exome sequencing, Sanger sequencing, and comprehensive bioinformatics analyses were performed. Seven DNAH11 heterozygous variants, which involved evolutionarily conserved residues and were predicted to exert deleterious effects, reduce protein stability, change protein conformation, and affect non-covalent residue's interactions, were identified as potential pathogenic factors responsible for these patients, respectively. In patient 1, three variants in compound heterozygotes, c.[3541A > G];[4334G > A;12428T > C] (p.[(Ser1181Gly)];[(Arg1445Gln;Met4143Thr)]), were confirmed. In patient 2, two variants in potential compound heterozygotes, c.2912A > G(;)7980A > T (p.(Asp971Gly)(;)(Gln2660His)), were detected. In patient 3, two variants in compound heterozygotes, c.[845T > C];[11402C > G] (p.[(Met282Thr)];[(Pro3801Arg)]), were confirmed. The phenotypes observed in these patients are consistent with typical/probably atypical PCD or DNAH11-associated ciliopathy, although functional validation is needed to confirm variant pathogenicity. These findings expand the phenotypic spectrum of DNAH11 variants and may facilitate more accurate genetic diagnosis and counseling.

The severe acute respiratory syndrome coronavirus 2 spike glycoprotein enables infection through a key conformational transition that exposes its receptor binding domain (RBD). Experimental evidence indicates that spike mutations, particularly the early D614G variant, alter the rate of this conformational shift, potentially increasing viral infectivity. We conducted extensive weighted ensemble simulations of the Ancestral, Delta, and Omicron BA.1 spike strains to investigate relationships between sequence mutations and RBD opening dynamics. We observe that Ancestral, Delta, and Omicron BA.1 spike RBDs open differently. Via dynamical network analysis, we identified two allosteric communication networks connecting all S1 domains: the established N2R linker and a newly investigated antiparallel R2N linker. In Delta and Omicron BA.1 variant spikes, RBD opening is facilitated by both linkers, while the Ancestral strain relies predominantly on the N2R linker. In the Ancestral spike, the D614-K854 salt bridge impedes allosteric communication through the R2N linker, whereas the loss of this salt bridge in all subsequent variants of concerns allows for increased local flexibility, thereby accelerating RBD opening. Hydrogen-deuterium mass spectrometry experiments validate these altered dynamics in the D614 region. This study unveils a "hidden" network, connecting the N-terminal domain to the RBD via the 614-proximal region, and the D614G mutation reshapes the fitness landscape of these critical viral glycoproteins.