We explored whether docetaxel (DTX) induced ferroptosis in castration-resistant prostate cancer (CRPC) cells and further investigated its mechanism of action and its regulation of the tumor immune microenvironment.

First, DTX-induced characteristic changes in the morphology, metabolism and protein expression of CRPC cells as well as electron microscopy ultrastructure were used to verify the occurrence of ferroptosis. Then, through transcriptome sequencing and gene set enrichment analysis, the nuclear factor erythroid 2-related factor 2 (NRF2) gene was screened out according to the differentially expressed genes and their key signaling pathways. Silencing NRF2 (si-NRF2) to explore its regulatory mechanism on DTX-induced ferroptosis in CRPC cells. Finally, TFRC-CAR-T cells combined with DTX were constructed to explore their antitumour ability and immune regulation.

The cell viability of CRPC cells decreased with increasing DTX concentration, and this downwards trend could be partially rescued by ferroptosis inhibitor (ferrostatin-1). Intracellular lipid reactive oxygen species and malondialdehyde levels were significantly increased in DTX-induced CRPC cells, while the levels of glutathione and glutathione peroxidase activity were significantly decreased. Transmission electron microscopy reveals marked mitochondrial shrinkage, spheroidal remodeling, and membrane densification. Transcriptome sequencing and gene set enrichment analysis revealed that the NRF2 gene in the antioxidant stress pathway is primarily involved in regulating ferroptosis. Immunohistochemistry and cytological Western Blot showed DTX chemotherapy activates NRF2 while also up-regulating transferrin receptor (TFRC) in CRPC cells. si-NRF2 gene enhance the sensitivity of DTX-induced ferroptosis in CRPC cells. The killing effect of TFRC-CAR-T cells alone on CRPC cells was weak, while DTX combined with TFRC-CAR-T cells demonstrated stronger killing ability and enhanced cytokine secretion compared to DTX alone.

DTX induces ferroptosis in CRPC cells, a process negatively regulated by NRF2. DTX combined with TFRC-CAR-T cells had a stronger lethal effect to CRPC cells and increase cytokine secretion.

Public health emergency waivers enacted during the COVID-19 pandemic dramatically expanded telemedicine use. Expiration of these waivers would limit access to this convenient care option for older adults, but it is unknown how expiration would affect patients' burden of care, quantified as health care contact days (days receiving in-person care).

To measure the extent to which telemedicine days experienced by older adults enrolled in traditional Medicare may supplement in-person health care contact days and to estimate how telemedicine waiver expiration could increase the number of health care contact days.

This is a cross-sectional study of the 2022 Medicare Current Beneficiary Survey examining a nationally representative sample of community-dwelling adults aged 65 years or older enrolled in traditional Medicare. Data analysis was performed from March 2025 to March 2026.

The primary outcomes were total telemedicine days (days with any telemedicine service) and additional health care contact days if telemedicine waivers expired (telemedicine days converted to in-person contact days, assuming 100% substitution). Multivariable logistic and Poisson regressions evaluated associations between patient characteristics and the probability and rate of additional health care contact days.

Among 5151 community-dwelling older adults (weighted number, 27 321 585 individuals; mean [SD] age, 74.6 [7.0] years; 2496 female individuals [52.4%]), 1294 (weighted 22.7%) used telemedicine. Telemedicine use varied widely (median [IQR], 1 [1-3] telemedicine day; maximum, 91 days), with 10.5% of telemedicine users (135 respondents) accounting for 50% of all telemedicine days. If telemedicine waivers expired and all affected telemedicine services were substituted with in-person services, 74.1% of older adults (951 respondents) using telemedicine would experience at least 1 additional health care contact day, totaling 8 772 118 additional contact days. Having more chronic conditions (adjusted odds ratio for >10 conditions, 8.42; 95% CI, 5.44-13.00) and difficulty getting places (adjusted odds ratio, 1.29; 95% CI, 1.10-1.53) were associated with higher odds of additional contact days.

This cross-sectional study of older adults enrolled in traditional Medicare found that most older adults using telemedicine would experience additional health care contact days if telemedicine waivers expired and all affected telemedicine services were substituted with in-person services. The resulting burden would fall disproportionately on adults with multiple chronic conditions and difficulty getting places, potentially exacerbating access barriers for patients most in need of care.

There is conflicting evidence for associations between maternal SARS-CoV-2 infection and neonatal congenital anomalies. Population-based studies evaluating confirmed maternal infection during pregnancy and at specific gestational time periods are needed.

To evaluate associations between laboratory-confirmed maternal SARS-CoV-2 infection in pregnancy and neonatal congenital anomalies, overall during pregnancy and by specific trimester of exposure.

This population-based, matched cohort study of live births with maternal SARS-CoV-2 infection in pregnancy matched 1:4 to live births without maternal infection in Ontario, Canada, was conducted from December 14, 2020, to December 31, 2021. Matching was performed on maternal age, delivery date, gestational age at birth, neonatal sex, and prepregnancy diabetes. Analyses were conducted from May to August 2025.

Maternal SARS-CoV-2 infection in pregnancy confirmed by positive real-time polymerase chain reaction (RT-PCR) test. Pregnancies with no positive RT-PCR test were considered SARS-CoV-2 negative.

The primary outcome was any neonatal congenital anomaly. The secondary outcome was any neonatal cardiac anomaly. Crude incidence rates of congenital anomalies per 1000 live births by maternal SARS-CoV-2 infection status with 95% CI were determined with a Poisson distribution for the study sample overall, and by each trimester of exposure.

A total of 5049 live births with corresponding maternal SARS-CoV-2 infection in pregnancy (mean [SD] maternal age, 31.0 [4.9] years) were matched 1:4 to 20 196 live births without maternal infection (mean [SD] maternal age, 31.1 [4.7] years). Compared with patients without infection, those with infection were more likely to be immigrants and to have high levels of material deprivation and were less likely to receive COVID-19 vaccination and live in rural areas. The crude incidence rate of any congenital anomaly was 32.5 anomalies per 1000 live births (95% CI, 27.9-37.9 anomalies per 1000 live births) with maternal SARS-CoV-2 infection and 31.1 anomalies per 1000 live births (95% CI, 28.8-33.6 anomalies per 1000 live births) without maternal SARS-CoV-2 infection (unadjusted rate ratio, 1.04; 95% CI, 0.87-1.24; P = .65). Multivariable logistic regression adjusting for maternal socioeconomic variables and prepregnancy COVID-19 vaccination did not alter these findings. Infection separately by trimester was not statistically significantly associated with the outcome. There were no statistically significant associations between maternal SARS-CoV-2 infection and cardiac anomalies in pregnancy overall or by trimester.

In this Ontario population-based study of 5049 live births with maternal SARS-CoV-2 infection matched to 20 196 live births without maternal infection, there was no association between laboratory-confirmed maternal SARS-CoV-2 infection and neonatal congenital anomalies in pregnancy overall, or by trimester of infection. These findings may provide reassurance to pregnant patients and their health care professionals, although further studies evaluating first trimester infection and risks of specific anomalies are warranted.

Asthma remains a major health challenge affecting over 300 million people worldwide, with severe, steroid-resistant phenotypes affecting 5-10% of patients who fail to respond to current therapies. This review examines the emerging role of Ly6G⁺Nur77⁺ lung macrophages in allergic airway inflammation and asthma pathogenesis, and discusses their potential as novel therapeutic targets.

Advances in single-cell RNA sequencing and high-dimensional profiling have revealed an atypical lung macrophage population co-expressing the granulocyte marker Ly6G and the orphan nuclear receptor Nur77 (Nr4a1). Despite surface expression of Ly6G, these cells exhibit macrophage morphology (CD64⁺, F4/80⁺, MerTK⁺) and are distinct from neutrophils. They sense allergens via protease-activated receptor 2 (PAR2) and initiate early Type-2 immune responses by promoting dendritic cell migration through cysteinyl leukotriene production. In animal models, loss of Nur77 signaling exacerbates airway hyperresponsiveness, eosinophilic inflammation, and mucus hypersecretion, indicating a protective regulatory function. Conversely, chronic activation of these cells contributes to pathological airway remodeling via arginase-1-mediated collagen deposition and fibrosis. Human translational data link reduced Nur77 expression to asthma severity and steroid resistance. Ly6G⁺Nur77⁺ lung macrophages represent a functionally distinctmacrophage population with a dual role in asthma, acting as early sentinelsthat initiate allergen-driven Th2 responses while also exerting regulatorycontrol over inflammation resolution. Their involvement in both protectiveand pathological pathways positions them as promising targets for endotype-specific therapeutic strategies in severe and steroid-resistant asthma.

Compare pressure values obtained from APAP titration with the final pressure (PF) selected by the clinician to approximate and optimize as much as possible our OSA patients treatment management.

Retrospective descriptive study in 114 OSA treated patients. After 2-3 months with empiric CPAP pressure, they underwent 2-3 nights with 2 different APAP devices to help clinicians to decide an APAP pressure according to percentile 95 (P95) and median (Pm) values after visual analysis. We selected 60 patients (30 for each device) meeting the inclusion criteria until our 3 months follow-up consultation when, according to clinical outcomes, final pressure (PF) is established. Data analysis was blind and random, by an experienced and independent sleep physician and how and why the clinicians used the APAP was statistically evaluated, measuring parameters from each device for every patient and combination of nights and comparing them with PF, whose correlation with AHI was also analyzed.

We found only significant evidence (p < 0.05) using Pm and Resmed device and considering AHI as a compliance predictive value, but no statistical difference (p > 0.05) performing more than one APAP night.

A single night of APAP titration and use of the median pressure may suffice to determine an optimal fixed CPAP setting in our patients. We discuss limitations including small sample size, exclusion of unstable patients and absence of laboratory PSG comparison and Spanish-specific practice patterns.

Stroke-associated pneumonia (SAP), which occurs in approximately 12%, is the most frequent infectious complication after acute stroke and a major contributor to morbidity and mortality. Despite its clinical importance, high-quality evidence to guide the diagnosis, prediction, prevention and treatment of SAP remains limited, underscoring the need for structured, consensus-based recommendations in stroke care. This guideline was developed following the standard methodology of the European Stroke Organisation (ESO): an interdisciplinary working group identified 15 clinically relevant questions, conducted systematic literature reviews and meta-analyses, appraised the quality of the available evidence and formulated evidence-based recommendations. Notably, only 3 of 15 questions were supported by predominantly low-quality evidence, and most guideline statements therefore rely on expert consensus rather than evidence-based recommendations. For clinical practice, standardised diagnostic criteria are recommended, while chest CT and plasma C-reactive protein may provide additional diagnostic value. Clinical prediction scores and biomarkers demonstrate moderate to good discriminative performance, However, their routine use will depend on the availability of effective preventive measures. Prevention strategies include positioning, early mobilisation and individualised nutritional approaches. Dysphagia screening and swallowing management are established components of post-stroke care for SAP prevention and are addressed in a separate ESO guideline. Adjunctive therapies are not part of standard care but may be considered in selected patients. Preventive antibiotic therapy is not recommended due to a lack of benefit on SAP incidence or clinical outcomes, whereas empirical antibiotic treatment should be initiated promptly after diagnosis and guided by local protocols targeting aspiration-associated pathogens. In addition, this guideline provides a framework for future randomised trials aimed at improving the evidence base for SAP management.

Cystic fibrosis (CF) is a common, life-shortening genetic condition caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A class II CFTR gene variant, F508del, is the commonest CF-causing variant (found in up to 90% of people with CF (pwCF) in some populations). The F508del variant lacks meaningful CFTR function: the faulty protein is degraded before reaching the cell membrane, where it would normally transport salt across the epithelial membrane. Corrective therapy with CFTR modulators could benefit many pwCF. This review evaluates treatment with single modulators (monotherapy).

To evaluate the clinically important benefits and harms of CFTR modulator monotherapy in people of any age with cystic fibrosis with class II CFTR gene variants (most commonly F508del).

We last searched the Cochrane CF Trials Register and online trials registries on 27 June 2025. We also checked the reference lists of relevant articles for additional studies.

We included parallel-group randomised controlled trials (RCTs) comparing any single CFTR modulator to placebo or any other single CFTR modulator in pwCF of any age or disease severity with class II variants.

Our critical outcomes were survival, quality of life (total score and respiratory domain), and forced expiratory volume in one second (FEV₁ % predicted; relative and absolute change from baseline). Our important outcomes included adverse effects and time to first pulmonary exacerbation. We planned to assess outcomes in the immediate term, short term, and longer term.

We assessed risk of bias using the original Cochrane tool (RoB 1).

We analysed available data with RevMan using a fixed-effect model. We reported odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. For adverse events, we reported 99% confidence intervals (CIs); for all other outcomes, we reported 95% CIs. Where we were unable to analyse data, we reported the results narratively. We used GRADE to assess the certainty of the evidence.

We included 10 early-phase placebo-controlled RCTs (424 participants) assessing eight different drugs (4PBA, CPX, N6022, cavosonstat, lumacaftor, FDL169, GLPG2222, and riociguat) in adults; one 4PBA study additionally included adolescents (age ≥ 14 years). All participants were homozygous for F508del. The longest study lasted just 29 days, so we could only assess immediate-term outcomes. Only two studies received no funding from pharmaceutical companies. Our main results are for lumacaftor and cavosonstat, which were the only drugs selected for further investigation in subsequent studies.

Investigators reported no deaths, but also no clinically relevant improvements in quality of life. There was insufficient evidence to determine effects on any measure of lung function. No studies demonstrated differences in the risk of mild, moderate, or severe adverse effects, including pulmonary exacerbations, between CFTR modulator monotherapy and placebo. The clinical relevance of adverse effects is difficult to assess, because each occurred in only a few participants per trial. We assessed the certainty of the evidence for two comparisons (lumacaftor versus placebo and cavosonstat versus placebo), rating the certainty of the evidence to be very low.

There is a lack of evidence to support monotherapy with a CFTR modulator for pwCF who have two F508del variants (F508del/F508del).

This review was completed under a programme of work that is part of the CF Foundation grant funding for Cochrane CF.

The protocol was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/view/CRD420251090914).

In patients with chronic respiratory failure and a stable oxygen requirement ≤4 L/min, switching from liquid oxygen to oxygen concentrators represents a potential strategy to optimize home oxygen therapy, although structured real-world experiences remain limited. This study describes the experience of the COMBO Project implemented by the Turin City Local Health Authority, aimed at the planned implementation of a therapeutic switch from liquid oxygen to oxygen concentrators and the assessment of its organizational and management outcomes. A retrospective descriptive-comparative observational study was conducted by comparing two periods (May-December 2023 and May-December 2024). A total of 129 patients eligible for the therapeutic switch were analyzed; for patients who completed the transition, a descriptive counterfactual scenario was developed to estimate the expected economic impact. The switch was successfully completed by 104 patients (80.6%). During the observation period, a 69% increase in the use of oxygen concentrators and a 3.9% reduction in liquid oxygen consumption were observed. Comparison with the counterfactual scenario showed an expected cost reduction of 2.56%. The main critical issues related to the transition process involved clinical, logistical, and prescribing aspects among patients who did not complete the switch. The COMBO Project experience demonstrates the feasibility of a structured therapeutic switch model in territorial healthcare settings; the value of the intervention lies primarily in process organization and in the coordinating role of the Territorial Pharmaceutical Service, while the observed economic impact should be interpreted as an expected benefit. The model appears potentially replicable in similar healthcare contexts.

Pulmonary rehabilitation (PR) is recommended internationally for individuals with chronic obstructive pulmonary disease (COPD), but there is limited evidence and practice of PR in Sri Lanka. Key challenges for PR such as poor accessibility, uptake and completion need to be addressed when designing and delivering new PR programmes. Accordingly, this study determined the feasibility and acceptability of culturally adapted PR for adults with COPD in Sri Lanka.

A randomized controlled feasibility trial was conducted with 50 adults living with COPD in Colombo, Sri Lanka. A culturally adapted PR comprised a 6-week rolling programme with sessions conducted twice every week. Sessions involved endurance and resistance exercise training, education and cultural adaptations of nutritional support and group singing. The control group received usual care, which did not include any form of PR or exercise training. Feasibility was determined by uptake (≥60% of eligible participants consented) and completion (≥70% of recruited participants). Acceptability was explored by focus group discussions (FGDs) analysed thematically.

Seventy-nine eligible individuals (94% of screened) were referred in order to recruit 50 participants (63% uptake). The majority of participants in both intervention (72%, n=18) and control (64%, n=16) groups completed the study. Based on qualitative focus group discussions four themes emerged: (1) Increased knowledge following PR, including dispelling misbeliefs about COPD and improving medication adherence; (2) Perceived improvements in health following PR, including improved walking ability and reduced breathlessness (3) Enjoyment and benefits of cultural adaptations to PR, and (4) Challenges during PR, including adherence to exercise and travel requirements.

Culturally adapted PR was feasible and acceptable to adults with COPD in Sri Lanka. A fully powered trial is warranted for evaluating clinical and cost-effectiveness of culturally adapted PR.

The study objective was to compare right and left heart morphology and function in dogs with compensated chronic right ventricular (RV) pressure overload secondary to pulmonic stenosis (PS) and chronic precapillary pulmonary hypertension (cPCPH).

This cross-sectional observational retrospective study included 64 client-owned dogs, including healthy controls (n = 15) and groups with PS (n = 31) and cPCPH (n = 18). The RV pressure gradient (RVPG) was determined by peak pulmonic or peak tricuspid regurgitation velocity and needed to be > 55 mmHg. Echocardiographic parameters assessing RV size [indexed diameter (RVIDd/Ao), area (N-RVAd) in diastole], hypertrophy [(RVFWd/LVFWd), (RVFWd/RVIDd)], and systolic function [fractional area change (RVFAC), indexed area in systole (N-RVAs)] were documented. Interventricular septal flattening was assessed using left ventricular (LV) eccentricity index (EI).

The RVPG was lower in cPCPH compared to PS [91 mmHg (55 to 158 mmHg) vs 108 mmHg (56 to 219 mmHg); P = 0.022]. The cPCPH group displayed more dilated [RVID/Ao: 0.13 (0.09 to 0.25) vs 0.10 (0.07 to 0.19), P = 0.004; N-RVAd: 1.17 (0.65 to 1.66) vs 0.83 (0.45 to 1.45), P = 0.010] and less hypertrophied RV [RVFWd/LVFWd: 0.9 (0.44 to 1.4) vs 1.0 (0.75 to 2.0), P < 0.020; RVFWd/RVIDd: 0.30 (0.19 to 0.55) vs 0.44 (0.24 to 0.67), P < 0.001], RV with poorer systolic function [N-RVAs: 0.69 (0.27 to 1.23) vs 0.35 (0.16 to 0.92), P = 0.001; RVFAC: 0.37 (0.14 to 0.66) vs 0.57 (0.29 to 0.71), P = 0.004], and more interventricular septal flattening [EIs:1.5 (1.09 to 5.71) vs 1.22 (0.88 to 2.1), P = 0.013] compared to PS. The RVID/Ao, N-RVAd, N-RVAs, RVFAC, RVFWd/RVIDd, and EIs were influenced by RVPG and the cause of RV pressure overload (independent of RVPG). Tricuspid regurgitation was more commonly observed in dogs with cPCPH.

After adjusting for RVPG, dogs with PS had less RV dilation, better RV function, and less left heart compromise compared to dogs with cPCPH.