To systematically explore the potential causal relationships among gene expression, DNA methylation, and chronic obstructive pulmonary disease (COPD) susceptibility using a multi-omics Mendelian randomization (MR) framework, and to further investigate key regulatory genes and methylation sites potentially involved in COPD pathogenesis.

We integrated genome-wide association study (GWAS) data from 635,145 individuals, expression quantitative trait loci (eQTL) data (N=15,695) from the eQTLGen Consortium, and methylation quantitative trait loci (mQTL) data from the Genetics of DNA Methylation Consortium (GoDMC). Two-sample Mendelian randomization was performed using genome-wide significant, linkage disequilibrium (LD)-independent (P < 5×10^-⁸, r² < 0.1) instruments filtered by Steiger analysis. Sensitivity analyses included inverse-variance weighted (IVW), MR-Egger, weighted median, and leave-one-out approaches. Colocalization analysis (posterior probability H₄ ≥ 0.75) and summary data-based Mendelian randomization (SMR) with heterogeneity in dependent instruments (HEIDI) test (P > 0.05) were used to validate shared causal variants. A three-step Mendelian randomization assessed mediation through methylation, gene expression, and COPD risk.

We identified eight putative causal genes for COPD based on Mendelian randomization and colocalization analyses. SDK1 demonstrated consistent statistical significance across all subsequent steps. Increased SDK1 expression was significantly associated with a reduced risk of COPD (β = -0.124, P = 0.002). Methylation at the intronic CpG site cg07526904 within SDK1 was associated with lower SDK1 expression (β = -0.148, P = 0.002) and elevated COPD susceptibility (β = 0.036, P = 0.038). Mediation analysis indicated that SDK1 expression mediated approximately 51.9% of the total effect of cg07526904 on COPD risk (β = 0.018, P = 0.038), supporting a potential epigenetic pathway.

This analysis suggests that SDK1 methylation may affect COPD risk by regulating gene expression, highlighting a potential epigenetic mechanism. These findings offer preliminary insights into COPD pathogenesis and may help identify targets for future biomarker-based interventions.

Vaccines are a cornerstone of modern medicine, however, in some regions, low coverage is reported in patients with chronic diseases, including people with cystic fibrosis (pwCF), compared to the general population.

This retrospective multicenter study in Israel included pwCF born after January 1, 2000, and compared them to the general population. Vaccination data were collected from patient databases and the Ministry of Health reports for the general population.

Out of 269 eligible pwCF aged 6 months to 23 years, a total of 173 were included. Coverage for the initial DTaP-IPV-HiB vaccine, administered in the first year of life, was similar between pwCF and the general population (92% compared with 96%, p = 0.23). In contrast, coverage for other routine vaccines given in the first year of life was significantly lower in pwCF: HAV (76% compared with 92%), HBV (85% compared with 96%), and the first dose of MMRV (85% compared with 97%) (all p < 0.001). Booster dose coverage for DTaP-IPV-HiB and MMRV, given at age 6-7 years, was also significantly reduced in pwCF (72% compared with 95% and 68% compared with 96% respectively, p < 0.001). Pneumococcal conjugate vaccine uptake was significantly lower in pwCF (61.8% vs. 94% in the general population p < 0.001), while the 23-valent pneumococcal vaccine was slightly more prevalent among pwCF compared to those with other chronic conditions, although uptake was low in both groups (15% vs. 10%, p = 0.001). Influenza vaccination rates during 3 seasons were significantly higher in pwCF (65%-70% vs. 20-27% in the general population, p < 0.001), whereas COVID-19 vaccine uptake was lower in adolescent pwCF compared to their general population peers (38.5% vs. 57.4%, p = 0.04).

Our study highlights suboptimal vaccine coverage among pwCF, particularly after the first year of life, affecting both routine early-life vaccines and booster doses. Greater awareness and proactive measures are needed to ensure adequate vaccination.

There is a scarcity of data on the utilization of thoracotomy for lung pathology in children in low- and middle-income countries (LMICs). These countries have high burdens of infectious diseases, especially tuberculosis, hydatic disease and Human immunodeficiency virus (HIV).

This is a retrospective descriptive study reviewing the indications for thoracotomy in a single center in a LMIC country. The study included all children under the age of 13 who underwent thoracotomy for pulmonary disease or vascular conditions affecting the airways at Tygerberg Hospital between January 2018 and December 2022. The indications for thoracotomy were classified into five groups: infectious, congenital, diagnostic, traumatic or neoplastic. Data collected included age, sex, HIV status, indication for the thoracotomy, procedures performed, complications of surgery and the final diagnosis after surgery.

One hundred seventy-two children who had undergone thoracotomy were studied with 182 thoracotomies performed. Infectious diseases (54.9%) were the most common indication for thoracotomy followed by congenital (35.2%), diagnostic (4.9%), traumatic (3.3%) and neoplastic (1.6%). The most common indication for thoracotomy was airway compression due to tuberculosis (TB) lymph nodes (21.4%), followed by hydatic cysts (20.9%) and vascular malformations (11.5%).

LMICs still face a significant burden of infectious and congenital diseases requiring thoracotomy, as compared to higher-income countries where neoplastic indications are most common. During the study period, hydatid cysts have become more prevalent and is now the most common indication for thoracotomy in the study setting. Thoracotomy can be safely performed in an LMIC setting with low morbidity and mortality, also in HIV-positive children.

China has entered the peak of COVID-19 infections following the release of the Notice on Further Optimizing and Implementing Prevention and Control Measures for COVID-19 Pneumonia on December 7, 2022. Most medical staff were infected with COVID-19 and have worked and lived in a higher-intensity stressful environment for a long time. Evidence suggests that resilience levels during public health emergencies are influenced by a variety of factors. The aim of this study was to investigate the status quo and relationships between self-efficacy, perceived stress, and resilience of medical staff during public health emergencies, and to explore the mediating role of self-efficacy between perceived stress and resilience.

Convenience sampling was used to recruit medical staff from a tertiary general hospital in Yunnan Province between December 15, 2022, and January 31, 2023. A total of 564 medical staff were including the study. A General Information Questionnaire, the General Self-Efficacy Scale, the Perceived Stress Scale, and the Resilience Evaluation Scale for medical staff were used to investigate them. Descriptive statistics were conducted using SPSS, and mediation analysis was performed using Model 4 of the PROCESS macro program with Bootstrap method.

Self-efficacy and perceived stress were both positively correlated with resilience (r = 0.561,0.273, P < 0 0.001). Perceived stress had a significant effect on self-efficacy (β = 0.411, P < 0.001), while perceived stress had no significant effect on resilience (β = 0.051, P = 0.181). Self-efficacy had a significant effect on resilience (β = 0.541, P < 0.001). Self-efficacy played a complete mediating role between perceived stress and resilience, accounting for 81% of the total effect of perceived stress on resilience.

Medical staff exhibited high levels of perceived stress, while their self-efficacy and resilience were at a middle level during public health emergencies. Given the complete mediating effect of self-efficacy, it is crucial to incorporate self-efficacy into interventions designed to improve medical staff's resilience. Therefore, the implementation of interventions that can enhance self-efficacy may help to improve the resilience levels of medical staff in high-pressure environments, thus promoting their psychological adaptation.

Pneumonia remains a major cause of morbidity and mortality, particularly in low- and middle-income countries, such as Pakistan. In this study, we aimed to examine the spatial and temporal patterns of pneumonia incidence in South Punjab, Pakistan, and to analyze their association with socio-ecological factors.

We used case report data from the district health information system (DHIS) over the years 2016 to 2020 and applied global and local Moran's I to identify spatial autocorrelation. Furthermore, we employed hot and cold spot analysis to identify significant areas with high and low pneumonia incidence. We used Emerging Hot Spot Analysis (EHSA) and time series clustering to examine shifting and temporal patterns of incidence, respectively. In addition, Generalized Linear Regression (GLR) and Multiscale Geographically Weighted Regression (MGWR) models were used to analyze geographic variation in the association of socio-ecological factors and pneumonia incidence.

Our results showed no significant global clustering of pneumonia incidence. Local Moran's I identified a low-low cluster in DG Khan, while Hot Spot Analysis detected one hot spot in Rajanpur. Multan City showed higher case counts, but this reflected population concentration rather than elevated incidence rates. The temporal analysis confirmed a significant seasonal variation, as well as a decrease in certain Tehsils and an increase in others. Our MGWR model revealed that better female literacy reduced incidence rates of pneumonia, whereas poor housing quality increased incidence rates of pneumonia, particularly in the southwestern areas of South Punjab.

We conclude that socio-ecological variables significantly influenced the incidence of pneumonia in South Punjab, and this association varies substantially over time and space. Our results emphasize the need for locally specific public health interventions to minimize pneumonia incidence in vulnerable populations in Pakistan. Our spatial epidemiological approach can be adapted to other regions of Pakistan and similar socio-ecological contexts in low- and middle-income countries.

Increasing reports and case series describe cases of endogenous endophthalmitis (EE) following severe acute respiratory syndrome coronavirus 2 infection. Endogenous endophthalmitis is a severe ophthalmologic pathology caused by bacteremic or fungemic seeding of the eye, often in immunocompromised patients. Delayed treatment can lead to permanent visual impairment. We report the diagnosis and management of a case of fungal endogenous endophthalmitis with voriconazole and surgery that led to complete visual acuity recovery.

We present a case of post-coronavirus disease 2019 bilateral fungal endogenous endophthalmitis due to Candida albicans in a 64-year-old Caucasian male patient. Upon arrival, he had a visual acuity of 6/200 and slow pupillary light reflex. Ocular examination revealed conjunctival hyperemia, keratic precipitates, moderate vitritis with cotton wool spots, intraretinal hemorrhages, and foci of chorioretinitis.

Treatment for endogenous endophthalmitis is often delayed because cultures frequently yield negative results. Early diagnosis is key for better outcomes in endogenous endophthalmitis. This case highlights the need for a high index of suspicion for endogenous endophthalmitis in patients with coronavirus disease 2019 to ensure early diagnosis and timely intervention.

Surgery is an effective treatment for chylothorax, particularly in cases of high-output chylothorax. However, precisely locating the thoracic duct for ligation and observing the surgical outcomes intraoperatively remains a challenge for surgeons. In this study, we demonstrated the feasibility of using Near-infrared (NIR) fluorescence imaging for thoracic duct ligation following indocyanine green (ICG) injection. Five patients with chylothorax who underwent surgery at our center were retrospectively included in this study. Of these, two had postoperative chylothorax following esophageal cancer surgery, one had postoperative chylothorax following lung cancer surgery, and two had spontaneous chylothorax. All patients received inguinal lymph node injections of ICG and subsequently underwent thoracic duct ligation under NIR-guided video-assisted thoracoscopic surgery (VATS) after anesthesia. All patients underwent NIR-guided ICG injection followed by VATS thoracic duct ligation. Four patients were operated on via the right side and one via the left side. The mean operative time was 62 min, the mean SBR value was 4.19, the mean postoperative drainage was 229.6 ml/day, the mean duration of postoperative chest drainage was 6.2 days, and the mean hospital stay was 17.8 days. None of the patients experienced recurrence of chylothorax postoperatively or during follow-up. In conclusion, NIR combined with ICG injection is highly effective in exploring and exposing the thoracic duct, as well as in determining the surgical outcome of thoracic duct ligation in real time.

Sweden's healthcare system, known for its equity and efficiency, faced criticism in the early months of the COVID-19 pandemic due to its high mortality rate compared to other Nordic countries. This study aims to explore the Swedish public health system's response to emerging respiratory infectious diseases, particularly COVID-19, using a realist approach. It analyzes contextual factors, interventions, mechanisms, and outcomes to provide a comprehensive understanding of the response, including debates around voluntary versus mandatory measures and the protection of vulnerable groups such as older adults.

To explore how and why Sweden's socio-political and healthcare context influenced the interventions employed and their acceptability at both individual and collective levels.

A realist approach was employed, combining qualitative data from semi-structured interviews with 11 public health experts, including researchers and infectious disease specialists. Data were analyzed using both deductive and inductive approaches and interpreted through the Context-Intervention-Mechanism-Outcome (CIMO) framework.

Key contextual factors included high trust in authorities, political decentralization, and the structure of the healthcare system. Notable interventions involved targeted vaccination campaigns, recruitment of retired healthcare workers, and increased digitalization. Mechanisms driving outcomes included trust, acceptance, and stakeholder engagement, which facilitated adaptation and acceptability of interventions. Interviewees highlighted challenges related to the timing and adequacy of measures, particularly for older adults in long-term care.

While Sweden's public health response was effective in several areas, it faced challenges due to decentralization, voluntary non-pharmaceutical interventions, and workforce burnout. The realist approach highlights the importance of context-sensitive mechanisms such as trust and cooperation, and the need for stronger coordination and tailored strategies for vulnerable populations. These findings provide valuable insights for strengthening public health systems and pandemic preparedness globally.

Severe odontogenic infections (OIs), often associated with untreated dental caries, can lead to life-threatening complications. In Fiji, dental caries is highly prevalent, and during the COVID-19 pandemic, limited access to dental care may contributed to the progression of untreated lesions, potentially resulting in an increased number of severe OI cases. However, there is a lack of evidence from Fiji on this issue. Therefore, this study aimed to assess the impact of the COVID-19 pandemic on the presentation of patients with OIs.

A retrospective, multicenter hospital-based study was conducted in Fiji, involving 260 participants who presented with odontogenic infections (OIs) during two time periods: pre-COVID-19 (March 2019 to February 2020) and during COVID-19 (March 2020 to February 2021). Collected variables included patient demographics, clinical presentation, etiological factors, and admission status. Data were analyzed using SPSS, with descriptive statistics and association tests conducted at a significance level of 0.05.

No statistically significant difference in the overall number of patients presenting with OIs was observed during the COVID-19 period. A higher proportion of cases occurred in patients under 30 years of age (62.8%), among the i-Taukei ethnic group (69.2%), and those residing in urban areas (48.1%), with a nearly equal distribution between males and females. The majority of cases were managed as outpatients (60.4%). Most infections involved a single fascial space and presented with a single clinical sign or symptom (76.9%). Dental caries was identified as the most common cause of infection (90.4%). While CWM Hospital and Lautoka Hospital reported a reduction in patient numbers (9.7% and 25%, respectively), Labasa Hospital recorded a significant increase in cases (34.7%, p < 0.001).

There was no evidence of a change in the prevalence, admission rates, or severity of odontogenic infections (OIs) during the COVID-19 pandemic. However, a significant regional variation in patient distribution was observed, with Labasa Hospital experiencing a notable increase in cases, attributed to the absence of lockdown measures and COVID-related restrictions in that region.

The circulating proteome may provide insights into the pathobiology of idiopathic pulmonary fibrosis (IPF) and diagnostic or prognostic biomarkers. We applied liquid chromatography coupled to mass spectrometry to quantify the peripheral blood proteome in patients with IPF and identify proteins associated with disease severity and progression.

The IPF cohort comprised 299 patients from the IPF-PRO Registry. Controls (n = 99) without known lung disease had similar distributions of age, sex and smoking status to the IPF cohort. Proteins were measured in plasma collected at enrollment using an Evosep One coupled to an Orbitrap Exploris. Data were analyzed with Spectronaut 14 with a deep experimental spectral library and were log₂ transformed. Linear regression was used to compare protein abundances in the IPF versus control cohorts and identify proteins associated with disease severity measures at enrollment in the IPF cohort. Cox regression analyses were used to identify proteins associated with outcomes in the IPF cohort, split 75/25 into training and test sets. The false discovery rate was controlled at 5%.

Overall, 761 protein groups corresponding to 736 unique genes were detected. Of these, 168 protein groups were significantly different in abundance in the IPF versus control cohorts, of which 39 were ≥ 1.3-fold different. Among the top differentially expressed proteins were surfactant protein B (SFTPB), secretoglobin family 3A member 1, intercellular adhesion molecule 1, thrombospondin 1 and platelet factor 4. In patients with IPF, greater abundance of apolipoprotein A-1 was statistically significantly associated with higher forced vital capacity % predicted at enrollment, while greater abundance of fibulin-1 was statistically significantly associated with lower diffusing capacity of the lungs for carbon monoxide % predicted. Multivariable models selected 4 proteins (SERPINA7, SFTPB, alpha 2 HS glycoprotein, kininogen 1) and 3 clinical factors that best discriminated the risk of respiratory death or lung transplant in patients with IPF, with a C-index of 0.78 in the training set and 0.72 in the test set.

Mass spectrometry-based proteomic analysis of data from the IPF-PRO Registry confirmed proteins previously associated with the presence, severity and progression of IPF and revealed new candidate biomarkers.

ClinicalTrials.gov; No: NCT01915511; registered August 5, 2013; URL: www.

gov .