Loneliness affects 12% of older adults globally, with concerns exacerbated by the COVID-19 pandemic. While digital health interventions (DHIs) show promise, evidence of their effectiveness remains mixed.

A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted in the PubMed, Cochrane, Web of Science and Embase databases (2010-25). Inclusion criteria were adults aged 60 years, with loneliness as the primary or secondary outcome. Study quality was assessed using GRADE and Cochrane risk of bias tools. Subgroup analyses explored intervention type, measurement scales, national development level, pandemic timing and some secondary outcomes.

Seventeen studies (n = 2423) showed DHIs significantly reduced loneliness scores (standardized mean difference [SMD] = -0.39, 95% CI -0.77 to -0.01). Subgroup analyses revealed significant reductions for social cognitive training (SMD = -0.82, 95% CI -1.47 to -0.16). Greater effectiveness was observed in developed countries (SMD = -0.30, 95% CI: -0.51 to -0.09) and during the pandemic period (SMD = -0.54, 95% CI: -1.03 to -0.06). DHIs also improved mental health (SMD = 0.98, 95% CI: 0.12 to 1.84) and marginally reduced depressive symptoms (SMD = -0.73, 95% CI: -1.45 to 0.00).

DHIs show promise in reducing loneliness scores among older adults, particularly through cognitive-focused interventions in supportive digital environments. However, the overall effect is modest and highly heterogeneous, with benefits that appear context-dependent and short-lived. Future research should prioritise standardised measurement, diverse populations and long-term follow-up to optimise DHI design.

Intravitreal injections are an essential treatment modality for retinal vascular and macular diseases, yet nationwide evidence describing long-term trends, regional variation, drug composition, seasonality, and the impact of the COVID-19 pandemic in Japan remains limited. We conducted a nationwide retrospective observational study using aggregated National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data for fiscal years (FYs) 2017-2022 (April-March). Total intravitreal injection procedures were identified using procedure code G016, and drug-specific counts of aflibercept, ranibizumab, brolucizumab, and faricimab were extracted using drug codes. Crude utilization rates (per 100,000 population) were calculated using official population estimates. Annual trends were assessed using linear regression, regional variation was summarized descriptively and compared across predefined geographic groupings, monthly patterns were evaluated using Friedman tests, and the pandemic impact was examined by comparing FY 2019 (pre-COVID), FYs 2020-2021 (COVID period), and FY 2022 (post-COVID). National total intravitreal injection procedures (G016) increased from 600,068 in FY 2017-936,715 in FY 2022 (anti-VEGF injections: 591,469-929,704), corresponding to an average increase of approximately 65,000 injections per year. The mean crude utilization rates rose from 478.6 ± 109.2 to 775.7 ± 143.1 per 100,000 population, while relative inter-prefectural variability decreased modestly (coefficient of variation 0.228 to 0.184). Aflibercept remained the predominant anti-VEGF agent, with diversification after the introduction of brolucizumab (FY 2020) and faricimab (FY 2022). Monthly volumes showed modest seasonality, with higher counts toward the end of the fiscal year. Injection volumes showed no marked decline during the pandemic; April-May 2020 totals (119,100 injections) were only 0.9% lower than the same months in 2019 (120,202 injections). These findings indicate sustained growth in intravitreal injection activity in Japan, persistent but modestly narrowing regional variation, and maintenance of injection services during COVID-19.

Pulmonary rehabilitation (PR) for patients with chronic obstructive pulmonary disease (COPD) improves exercise tolerance and COPD assessment test score (CAT). Oxygen supplementation during PR facilitates exercise physiological benefits. This study aimed to assess the feasibility of a trial comparing two oxygen supplementation methods, with the hypothesis that both would be effective and produce distinct outcomes.

This double-blind, crossover, randomized controlled trial compared two PR programs-Program A (including PR under FiO₂ 0.3) and Program B (including PR under FiO₂ 0.5)-using high-flow nasal cannula oxygen therapy in patients with COPD and exertional dyspnea (n = 6). Data on the 6-minute walk distance (6MWD), CAT, muscle strength, body composition analysis, respiratory function, and joint range of motion were collected. Participants underwent one month of regular PR followed by two months of oxygen-supplemented PR, with data collected again after this period. Statistical significance was set at 0.05 with a power of 0.8, and the required sample size was calculated accordingly.

The required sample size could not be calculated based on the 6MWD. The improvement in CAT by Program A was greater than that by Program B. The improvements in muscle parameters by Program B were greater than those by Program A. The standardized effect size and the corresponding required sample sizes for the CAT, quadriceps muscle power, lower leg circumference, trunk muscle mass, and leg muscle mass were 0.32/81, 0.66/8, 0.17/114, 0.27/88, and 0.24/56, respectively.

Given the small number of participants, the 6MWD and CAT were not appropriate primary endpoints for comparing the effectiveness of the two oxygen supplementations during PR in patients with COPD. However, the quadriceps muscle power was identified as the most suitable primary endpoint among all the investigated parameters.

Since 2021, avian influenza A(H5N1) clade 2.3.4.4b viruses have spread widely among wild birds and domesticated poultry in the United States, with sporadic spillover into mammals. During November 2024-January 2025, 19 domestic cats in Los Angeles County, California, became ill after consumption of commercially purchased raw milk, raw meat, or raw pet food; nine cats tested positive for influenza A(H5N1) virus (clade 2.3.4.4b genotype B3.13). Overall, 139 persons were exposed to the 19 infected cats, and all were monitored for symptoms. Although 30 persons reported influenza-like illness symptoms, none received a positive influenza A(H5) reverse transcription-polymerase chain reaction (RT-PCR) test result. In April 2025, the Los Angeles County Department of Public Health and CDC invited all exposed persons to participate in an influenza A(H5N1) serosurvey to determine whether transmission of influenza A(H5N1) virus occurred, including in those without symptoms. Sera from 25 (18%) of the 139 exposed persons were tested. Among these, antibodies specific to A(H5N1) clade 2.3.4.4.b (antigenically similar to the clade 2.3.4.4.b influenza A[H5N1] virus isolated from the infected cats) were detected in serum from one veterinary professional, who was asymptomatic. This person did not use respiratory or eye protection during the exposure, did not report influenza-like illness after the exposure, and reported no other known risk factors for A(H5N1) infection. These findings represent serologic evidence of possible transmission of influenza A(H5N1) clade 2.3.4.4.b virus from a domestic cat to a human, highlighting concerns about potential cat-to-human transmission of influenza A(H5N1) virus and the importance of infection control practices in veterinary settings.

While systemic immune dysregulation is well-documented in HIV infection, its impact on blood and respiratory tract viromes remains poorly understood. This study characterizes HIV-associated alterations in viral communities and examines their clinical relevance. Using viral metagenomics, we compare 203 ART-treated HIV-positive individuals and 120 healthy controls. HIV infection significantly restructures the blood virome, shifting from bacteriophage dominance (96.2% in controls) to eukaryotic virus predominance (69.1%). Increased alpha diversity, significant β-diversity divergence, and heightened dispersion heterogeneity are observed in HIV cases. Consistent enrichment of Flaviviridae, Parvoviridae, and Anelloviridae is detected. Throat viromes maintain phage dominance (>90%) but exhibit strain-level diversification, including Microviridae proliferation. Network analysis reveals Retroviridae-Anelloviridae co-dynamics (r = +0.562) and identifies Picobirnaviridae as a key interactor. Functional analysis shows enriched viral replication and host modulation genes. Compartment-specific disruption patterns nominate Pegivirus C, parvovirus B19, and Anelloviruses as potential biomarkers. Cross-kingdom viral interactions suggest novel mechanisms influencing disease progression and support future virome-targeting adjunct therapies.

Pulmonary arterial hypertension (PAH) has a poor prognosis despite available treatments. TPN171H, structurally modified from traditional Chinese medicine (Epimedium), was reported to have a high affinity for phosphodiesterase type 5 and exhibited anti-inflammatory and vasodilatory effects in preclinical studies. This phase 2a randomized trial (NCT04483115) evaluated the hemodynamic effects and safety of TPN171H in PAH. Sixty patients with PAH were randomly assigned to receive placebo, TPN171H (2.5, 5, or 10 mg) or tadalafil (20 or 40 mg) and evaluated for hemodynamic changes for 24 h. The primary endpoint was the maximum change (%) in pulmonary vascular resistance (PVR) from baseline. The key secondary endpoint was the change (%) in PVR to systemic vascular resistance (SVR) ratio at each observation point from baseline. Compared to the placebo group, the least square mean differences in the maximum change in PVR were -16.8% (95% CI, -29.1 to -4.5, p = 0.008) in TPN171H 5 mg, -15.4% (95% CI, -28.2 to -2.7, p = 0.019) in tadalafil 20 mg, and -13.3% (95% CI, -25.6 to -0.9, p = 0.036) in the tadalafil 40 mg group. Moreover, TPN171H 5 mg, but none of the tadalafil doses, showed a significant reduction in PVR/SVR ratio at 2 h (p = 0.026), 3 h (p = 0.030), and 5 h (p = 0.046) compared to the placebo group. No serious adverse events occurred. TPN171H 5 mg demonstrated favorable acute hemodynamic effects and an acceptable short-term safety profile in this exploratory trial, supporting further evaluation in adequately powered trials.

The patient is a 66-year-old man. He came to our hospital with fever for two weeks. Based on blood sampling and abdominal computed tomography (CT) scan, a diagnosis of liver abscess was made, and antibiotic treatment was started, but symptoms did not improve, so percutaneous drainage was performed. One week later, he became dyspnea and chest CT scan revealed right pyothorax, so video-assisted thoracoscopic curettage was performed. It has been reported that liver abscesses are complicated by pyothorax in a few percent of cases. There are two hypotheses as to the mechanism. The one is the spread of inflammation from the liver abscess through the diaphragm into the pleural space, and the other is iatrogenic complication of percutaneous liver drainage.

Infective and noninfective pulmonary complications occur with biologic agents and targeted small molecule inhibitors used to treat immune-mediated inflammatory conditions. The most common lower respiratory tract infection is bacterial pneumonia. Opportunistic infections including tuberculosis can also occur at increased rates depending on the immunosuppressive agent, specific disease, and epidemiologic background of the patient. The most common noninfectious sequela is drug-induced interstitial lung disease.

Nerandomilast, a selective phosphodiesterase 4B (PDE4B) inhibitor, has been extensively investigated for the treatment of pulmonary fibrosis; however, its therapeutic potential and mechanisms of action in idiopathic inflammatory myopathies-associated interstitial lung disease (IIM-ILD) remain to be elucidated.

A myositis-associated ILD mouse model was treated with nerandomilast (BI 1015550), and lung pathology was assessed histologically. Human lung microvascular endothelial cells-5a were stimulated with neutrophil extracellular traps (NETs) to induce endothelial-mesenchymal transition (EndMT). Western blotting, immunofluorescence, qPCR and ELISA were employed to analyse pathways and cytokines.

PDE4B was upregulated in the lungs of patients with IIM-ILD and in mice. Treatment with BI 1015550 significantly reduced lung inflammation and fibrosis scores, decreased inflammatory cytokines in bronchoalveolar lavage fluid and serum, alleviated muscle inflammation and lowered kinase activity without evident hepatorenal toxicity. Immunofluorescence and immunohistochemistry revealed diminished NET markers, reduced inflammatory cell infiltration (CD3, CD11b, F4/80), suppression of EndMT, downregulation of Ras homolog family member A (RhoA) and inhibition of key fibrotic pathways: phosphorylated phosphoinositide 3-kinase (P-PI3K), phosphorylated protein kinase B (P-AKT), phosphorylated p38 mitogen-activated protein kinase (P-P38), phosphorylated extracellular signal-regulated kinase (P-ERK), phosphorylated nuclear factor kappa-B (P-NF-κB). In vitro, BI 1015550 inhibited phorbol 12-myristate 13-acetate-induced neutrophil extracellular trap formation (NETosis) and EndMT.

Nerandomilast alleviates IIM-ILD by inhibiting NET formation and suppressing EndMT in lung microvascular endothelial cells, potentially through non-Smad signalling pathway modulation and cAMP-PKA-RhoA pathway activation. These findings suggest that the specific inhibition of PDE4B is a potential therapeutic approach for IIM-ILD.

Coughing is a common clinical symptom and a protective respiratory reflex closely associated with various respiratory system diseases. The acoustic characteristics of cough sounds are influenced by underlying pathological factors, with distinct acoustic signatures corresponding to different etiologies. Through rigorous analysis of these sounds, rapid identification and preliminary diagnosis of related conditions may be achieved. This approach holds great potential for broad application in mobile health and ubiquitous health platforms.

This study aimed to explore the application of acoustic analysis of cough sounds in the diagnosis of respiratory diseases to enhance the diagnostic efficiency of health care professionals.

In this study, we conducted extensive data collection, including voluntary cough audio recordings from patients diagnosed with respiratory diseases (eg, chronic obstructive pulmonary disease, lung cancer, COVID-19, and pneumonia) and from healthy participants. A total of 2610 audio samples were collected. We incorporated a channel attention mechanism (CAM) into the final convolutional block of each residual block in the ResNet18 neural network, thereby constructing the CAM-ResNet18 neural network model. The recorded cough audio samples were converted into spectrograms to form the input dataset for model training. The CAM-ResNet18 model was trained on the training set of this dataset, with iterative parameter adjustments until convergence was achieved. Finally, spectrograms from the test set were fed into the pretrained model for accurate classification of the cough-related conditions.

Experimental results on the collected audio dataset demonstrate that the proposed CAM-ResNet18 model achieves an accuracy of 83.9% and an average F1-score of 82.52% in classifying 5 types of cough sounds. In comparison, the traditional ResNet18 model achieves an accuracy of 78.16% and an average F1-score of 78.29%, indicating a clear performance improvement with the integration of the CAM.

The experimental results validate the effectiveness of the proposed method, highlighting its significant potential for application in clinical diagnosis.