Hasil untuk "Diseases of the respiratory system"

C. Marras, J. Beck, J. Bower et al.

Estimates of the prevalence of Parkinson’s disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson’s disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537–614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood. A large study that combines data from five different projects in four different regions across North America provides an updated estimate of the prevalence of Parkinson’s disease (PD). Connie Marras at Toronto Western Hospital in Canada and colleagues found that PD prevalence among individuals over 45 years of age is higher among men than women and that it increases with age in both sexes. They estimate that the overall prevalence of PD is 572 per 100,000 and that in the US in 2010 there were 680,000 individuals with PD. As life expectancy increases this number is projected to increase to over one million by 2030. These figures, which the authors note should be considered minimum prevalence estimates, warn of the impact that PD will have on North America’s healthcare systems in the near future.

Cheng Liu, Lili He, Yuanhao Guo et al.

Abstract Background Beyond hemostasis, platelets’ immune and inflammatory role is recognized and thrombocytosis is generally regarded as a marker of the inflammatory response. However, the immune functions of platelets remain beneath the surface, and previous studies have reported conflicting findings regarding the significance of thrombocytosis in infection-related diseases. Can reactive thrombocytosis be viewed as a “higher-is-worse or higher-is-better” predictor of clinical outcome? Methods We analyzed 2754 patients discharged from the respiratory and infectious-disease wards between 1 January 2021 and 11 June 2025, and patients from the MIMIC-IV 3.1 database were used as validation cohorts, grouped by peak platelet counts (< 90, ≥ 400, 90–399 × 10⁹/L). Cox regression and multivariate logistic regression were performed to analyze the relationship between platelet count and in-hospital mortality. Multivariate linear regression was used to analyze the relationship between platelet count and length of hospital stay (LOS). Results Patients with reactive thrombocytosis had longer hospital stays (13 vs. 10 days; p < 0.001) and higher inflammatory markers than those with normal platelet counts CRP (90.2 vs. 28.6 mg/L; p < 0.001), PCT (0.195 vs. 0.092 ng/mL; p < 0.001), WBC (12.6 vs. 8.4 × 10⁹/L; p < 0.001). Despite these differences, mortality (3.4% vs. 4.4%) did not differ, nor did the rates of bloodstream, fungal, or polymicrobial infections. Clustering analyses confirmed comparable overall microbial spectra between the two groups. The impact of thrombocytosis on mortality (HR, 0.52; 95% CI, 0.27–0.99; p = 0.047) is context-dependent: it trended toward higher mortality in non-septic patients (OR, 1.42; 95% CI, 0.64–2.86, p = 0.357) but toward lower mortality in those with sepsis (OR, 0.33; 95% CI, 0.05–1.51, p = 0.18). The same opposing pattern and the interaction of sepsis and thrombocytosis re-emerged (OR, 1.70; 95% CI, 0.95–2.92, p = 0.063 vs. OR, 0.58; 95% CI, 0.34–0.96, p = 0.04) in MIMIC-IV data. Thrombocytopenia is an independent risk factor for mortality (HR, 2.08; 95% CI, 1.48–2.93; p < 0.001) and has good combined predictive ability. Conclusions Thrombocytosis trended toward higher mortality in non-septic patients yet toward lower mortality in those with sepsis.

Jason A. Galvis, Taylor B. Parker, Cesar A. Corzo et al.

Vehicle movements, including vehicle cabs and trailers, play a role in disseminating disease in swine production. However, there are many information gaps about vehicle movements patterns that increase the probability of disease transmission, which is crucial in developing better preventive strategies. In this study we described the movement pattern of vehicle cabs and trailers and identified risk factors for porcine reproductive and respiratory syndrome (PRRS) and porcine epidemic diarrhea (PED) farm's infectious status. We collected global positioning system (GPS) movement data from vehicle cabs and trailers for 18 months and basic information for 6621 farms in the U.S. For the vehicle movement data, we estimated 66 variables and evaluate their association with farms PRRS and PED status. Our univariate analysis showed that 56 variables were significant associated (p < 0.05) to PED and PRRS farm status. Within these variables, vehicle visit frequency and previous exposition to positive farms were the main risk factors for both diseases. Otherwise, increased vehicle cab and trailer loyalty for farm shipments and vehicle cleaning and disinfection events were protective factors. In the multivariate model, each additional weekly visit by a vehicle cab that had been exposed to a positive farm one day before the shipment was associated with a 234\% and 243\% increase in the odds of a farm testing PRRS- and PED-positive, respectively. Our analysis revealed that vehicle contact history play a crucial role in the transmission of PRRS and PED. These findings can provide insights to develop more target strategies aimed at reducing the transmission and outbreaks linked to vehicle movements in swine production.

P. Archambault, R. Rosychuk, M. Audet et al.

Professional Committee Of Spine And Spinal Cord In, Professional Committee Of Spine Chinese Associatio, The Second Medical-Rehabilitation Integration Work et al.

Vision Loss Expert Group of the Global Burden of Disease , the GBD 2019 Blindness and Vision Impairment Collabora

ABSTRACT Purpose To assess burden of blindness and visual impairment (VI) in Sub-Saharan Africa (SSA) as of 2020, the planned end point of the Vision 2020 program. Methods A systematic review and meta-analysis assessed burden, in the better eye, of blindness (presenting distance visual acuity, VA < 3/60), moderate and severe vision impairment (MSVI; VA < 6/18 but ≥ 3/60) and mild vision impairment (VA < 6/12 and ≥ 6/18); and also functional presbyopia (<N6 or N8 in the presence of ≥ 6/12 best-corrected distance visual acuity) in SSA. Results In 2020, an estimated 5,083,000 people (95%Uncertainty Interval, UI, 4,474,000–5,696,000) in SSA were bilaterally blind; 20442,000 more (95%UI 18,568,000–22,430,000) had MSVI. The age-standardized prevalence of blindness in SSA is the highest for any GBD super-region, nearly double the world average (0.99%, 95%UI, 0.85–1.12; vs 0.52%, 95% UI, 0.46–0.59 respectively). The Western (4.15%) and Eastern (3.79%) SSA sub-regions had the highest age-standardized prevalence of blindness for the 50+ age group amongst SSA sub-regions. Improvement in age-specific prevalence since 2000 was less than the Vision 2020 target (−25%) for all subcategories of VI; improvement in blindness was the only category close to the goal (about 80–100% of goal across SSA sub-regions). Conclusions The SSA age-specific prevalence of VI has generally improved since 2000, especially for blindness. However, the number of VI cases has increased with population growth and aging, and Vision 2020 targets were not met. Because most causes of VI require individual-level clinical care, large increases in training and eye care delivery systems development/financing are critical areas of focus.

O. A. Katsaraba, R. M. Sachuk, O. Ya. Dmytriv et al.

Laboratory studies were conducted to determine the subacute toxicity of the veterinary drug Loxidev in dogs. 1 ml of the drug contains the active substance: meloxicam – 20 mg, excipients – glycine, sodium hydroxide, meglumine, and water for injection – up to 1 ml. The drug Loxidev, based on meloxicam, is used in diseases of European fallow deer, treatment of animals for non-infectious diseases of the musculoskeletal system (acute aseptic myositis to reduce symptoms of lameness and inflammation), as well as for diseases of the respiratory system (in the case of appropriate antibiotic therapy). Red deer: treatment of animals for non-infectious diseases of the musculoskeletal system (arthritis of the metatarso-metatarsal joint to reduce symptoms of lameness and inflammation). It was established that subcutaneous administration of the drug Loxidev (solution for injection) to dogs in doses of 0.03; 0.15 and 0.3 ml/kg of body weight for 3 days in general does not affect the clinical and biochemical parameters of the blood and does not cause hepato- and nephrotoxic effects on the animal body under the conditions of a subacute toxicological experiment. The exceptions were the tendencies to reduce the concentration of total hemoglobin, hematocrit and erythrocyte count, as well as a significant decrease (P < 0.05) in the number of leukocytes by 6.6 %, respectively, relative to the control in the blood and an increase (P < 0.05) in the enzymatic activity of ALT and AST and the concentration of urea in the blood serum of dogs after three days of administration of the drug at a dose of 0.30 mg/kg of body weight by 19.4; 19.3 and 14.5 %, respectively, however, 7 days after discontinuation of the drug, these indicators did not significantly differ from the control. Further research directions will include the following: studying the long-term effects of meloxicam on the body of dogs to determine possible cumulative effects when used in long-term therapeutic courses; analysis of the molecular and cellular mechanisms underlying the identified toxic effects, for example, effects on enzyme systems, oxidative stress or immunological reactions; expanding studies with an emphasis on the specific effects of the drug on the liver, kidneys, cardiovascular system and digestive tract, which are the primary targets for NSAIDs; studying the effects of meloxicam on animal reproductive function, embryo development and potential risks to offspring.

Kai M. Beeh, Tim Harrison, Enrico Heffler et al.

Abstract Introduction Fractional exhaled nitric oxide (FeNO) is an important type 2 (T2) asthma biomarker. Home-based FeNO monitoring can provide longitudinal data better reflecting the variable nature of T2 inflammation versus single-point data. We sought to compare longitudinal mean FeNO and variability (CV) in relation to asthma control, and to compare detection rate of T2FeNO inflammation at diagnostic (≥ 40 ppb in GINA 1) and on-treatment (≥ 25 ppb in GINA 2–5) cutoffs during home versus clinic measurements. Methods This was an observational study with once-daily home-based FeNO (Vivatmo me) and symptom diary in patients with asthma of different GINA steps performed over 3 months. Clinic FeNO, forced expiratory volume in 1 s (FEV1), and 5-item asthma control questionnaire (ACQ-5) scores were also collected at two visits (enrolment/study end). Results We enrolled 85 patients (n = 23 step 1, n = 37 steps 2–3, and n = 25 steps 4–5). Mean FeNO over 3 months was highest in uncontrolled steps 4–5 (p = 0.006), and FeNO variability in steps 2–3 (p = 0.046). Subjects with optimal control (ACQ < 0.75 both visits) had comparable mean FeNO values, but fewer patients with CV above the median vs. suboptimally controlled patients (39.1% vs. 54.1%; p = 0.03). In GINA 1, FeNO CV was lower in optimally controlled patients (p = 0.10). Mean FeNO was higher on symptomatic asthma days, particularly in step 1 (p = 0.002), with similar trends during loss of asthma control phases. Home FeNO increased the detection rate of T2FeNO inflammation at a diagnostic cutoff (≥ 40 ppb, step 1) from 8.7% (clinic FeNO) to 47.8% of subjects, and of on-treatment T2FeNO inflammation in GINA steps 2–3 and 4–5 from 58.3% to 83.3%, and 64% to 96%, respectively. Conclusion Home-based FeNO provides important information about airway inflammation, distinct and complementary to symptom control. Detection of T2FeNO inflammation is facilitated at all GINA steps at diagnostic and predictive/prognostic cutoffs, with important implications for management and diagnosis. Trial Registration German Clinical Trial Register (DRKS) DRKS00029118, registered July 1, 2022.

Haokun Zhao, Yingzhe Bai, Qingyang Xu et al.

Accurate disease detection is of paramount importance for effective medical treatment and patient care. However, the process of disease detection is often associated with extensive medical testing and considerable costs, making it impractical to perform all possible medical tests on a patient to diagnose or predict hundreds or thousands of diseases. In this work, we propose Collaborative Learning for Disease Detection (CLDD), a novel graph-based deep learning model that formulates disease detection as a collaborative learning task by exploiting associations among diseases and similarities among patients adaptively. CLDD integrates patient-disease interactions and demographic features from electronic health records to detect hundreds or thousands of diseases for every patient, with little to no reliance on the corresponding medical tests. Extensive experiments on a processed version of the MIMIC-IV dataset comprising 61,191 patients and 2,000 diseases demonstrate that CLDD consistently outperforms representative baselines across multiple metrics, achieving a 6.33\% improvement in recall and 7.63\% improvement in precision. Furthermore, case studies on individual patients illustrate that CLDD can successfully recover masked diseases within its top-ranked predictions, demonstrating both interpretability and reliability in disease prediction. By reducing diagnostic costs and improving accessibility, CLDD holds promise for large-scale disease screening and social health security.

L Cif, D Demailly, JP Lin et al.

Heterozygous mutations in KMT2B are associated with an early-onset, progressive, and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal, and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5 to 37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke-Fahn-Marsden Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year, and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002, and P = 0.012).

Bosubabu Sambana, Hillary Sunday Nnadi, Mohd Anas Wajid et al.

Plant diseases pose significant challenges to farmers and the agricultural sector at large. However, early detection of plant diseases is crucial to mitigating their effects and preventing widespread damage, as outbreaks can severely impact the productivity and quality of crops. With advancements in technology, there are increasing opportunities for automating the monitoring and detection of disease outbreaks in plants. This study proposed a system designed to identify and monitor plant diseases using a transfer learning approach. Specifically, the study utilizes YOLOv7 and YOLOv8, two state-ofthe-art models in the field of object detection. By fine-tuning these models on a dataset of plant leaf images, the system is able to accurately detect the presence of Bacteria, Fungi and Viral diseases such as Powdery Mildew, Angular Leaf Spot, Early blight and Tomato mosaic virus. The model's performance was evaluated using several metrics, including mean Average Precision (mAP), F1-score, Precision, and Recall, yielding values of 91.05, 89.40, 91.22, and 87.66, respectively. The result demonstrates the superior effectiveness and efficiency of YOLOv8 compared to other object detection methods, highlighting its potential for use in modern agricultural practices. The approach provides a scalable, automated solution for early any plant disease detection, contributing to enhanced crop yield, reduced reliance on manual monitoring, and supporting sustainable agricultural practices.

Nathalia A. Loureiro, Camilo R. Neto, Jack Sutton et al.

Inter-city interactions are critical for the transmission of infectious diseases, yet their effects on the scaling of disease cases remain largely underexplored. Here, we use the commuting network as a proxy for inter-city interactions, integrating it with a general scaling framework to describe the incidence of seven infectious diseases across Brazilian cities as a function of population size and the number of commuters. Our models significantly outperform traditional urban scaling approaches, revealing that the relationship between disease cases and a combination of population and commuters varies across diseases and is influenced by both factors. Although most cities exhibit a less-than-proportional increase in disease cases with changes in population and commuters, more-than-proportional responses are also observed across all diseases. Notably, in some small and isolated cities, proportional rises in population and commuters correlate with a reduction in disease cases. These findings suggest that such towns may experience improved health outcomes and socioeconomic conditions as they grow and become more connected. However, as growth and connectivity continue, these gains diminish, eventually giving way to challenges typical of larger urban areas - such as socioeconomic inequality and overcrowding - that facilitate the spread of infectious diseases. Our study underscores the interconnected roles of population size and commuter dynamics in disease incidence while highlighting that changes in population size exert a greater influence on disease cases than variations in the number of commuters.

Mariza Fevereiro-Martins, A. C. Santos, Carlos Marques-Neves et al.

Retinal neurodevelopment, vascularization, homeostasis, and stress response are influenced by factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), and erythropoietin (EPO). As retinopathy of prematurity (ROP) is a neurovascular retinal disease, this study analyzed the contributions of NGF (rs6330), BDNF (rs7934165), TH (rs10770141), and EPO (rs507392) genetic functional polymorphisms to the modulation of hematological and biochemical parameters of the first week of life and their association with ROP development. A multicenter cohort of 396 preterm infants (gestational age < 32 weeks or birth weight < 1500 g) was genotyped using MicroChip DNA and iPlex MassARRAY® platform. Multivariate regression followed univariate assessment of ROP risk factors. NGF (GG) genotype was associated with a higher ROP risk (OR = 1.79), which increased further (OR = 2.38) when epistatic interactions with TH (allele C) and BDNF (allele G) were present. Significant circulating biomarker differences, including bilirubin, erythrocytes, monocytes, neutrophils, lymphocytes, and platelet markers, were found between ROP and non-ROP groups, with variations depending on the polymorphism. These findings suggest that NGF (rs6330) and its interactions with related genes contribute to ROP risk, providing valuable insights into the genetic and biological mechanisms underlying the disease and identifying potential predictive biomarkers.

Ibrahim Eker, Hamide Nur Çevik Özdemir, F. Yılmaz et al.

Objective Preimplantation genetic diagnosis (PGD) with human leukocyte antigen (HLA) typing represents a significant advancement in treating inherited hematological disorders, particularly thalassemia major. This technology enables the birth of healthy children who can serve as compatible stem cell donors for their affected siblings. Türkiye is a world leader in both PGD+HLA typing technology and hematopoietic stem cell transplantation (HSCT) from savior siblings born through PGD+HLA typing. This study investigated the experiences of Turkish parents who underwent successful savior sibling procedures using PGD+HLA typing and then successful HSCT from the savior sibling for the treatment of the child with thalassemia major. We aimed to understand the medical, psychological, and sociocultural dimensions of this complex process within the Turkish healthcare context. Materials and Methods A qualitative study was undertaken using a descriptive phenomenological approach. In-depth interviews were conducted with parents from 16 families who had successfully completed PGD+HLA matching and subsequent stem cell transplantation processes from the savior sibling to the child with thalassemia. Data were analyzed using Colaizzi’s seven-step method and MAXQDA 20.0 software. Results The analysis revealed six main themes: disease stage, treatment, recovery process, social/family, support systems, and recommendations. Parents reported significant emotional challenges but demonstrated unexpected resilience. Religious and cultural factors played nuanced roles, with most parents viewing the process as compatible with their beliefs. Economic burdens, prolonged hospitalizations, and geographical access to treatment centers emerged as key challenges. Extended family support and professional healthcare guidance were identified as crucial support mechanisms. Conclusion This study highlights the complex interplay between advanced medical technologies and traditional values in Turkish society. The findings emphasize the need for comprehensive and culturally sensitive support systems and long-term follow-up for families. The results suggest the value of implementing multidisciplinary care teams and developing specialized support programs for families undergoing savior sibling procedures.

Lê Thị Kim Cương, Hồ Thị Ngọc Hạnh, Cao Thị Hoài et al.

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of mortality and disability worldwide. Among elderly patients, COPD not only reduces quality of life but also places a significant burden on healthcare systems. Chronic inflammation plays a key role in the pathogenesis of COPD. In recent years, peripheral blood inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) have gained attention as useful tools for assessing inflammation and predicting disease prognosis. However, in Vietnam, especially among elderly patients- research on the role of NLR in monitoring and managing COPD remains limited. Therefore, we conducted the study titled: “Investigation of Neutrophil-to-Lymphocyte Ratio in Elderly Patients with Chronic Obstructive Pulmonary Disease at Thong Nhat Hospital”. To determine the NLR levels in elderly patients with COPD and evaluate the relationship between NLR and disease severity. Additionally, to compare NLR values across different patient subgroups based on factors such as age, gender, BMI, medication usage, comorbidities, and to investigate the correlation between NLR and the inflammatory marker               CRP. Sectional descriptive study conducted on elderly COPD patients visiting the respiratory outpatient clinic at Thong Nhat Hospital. From January 2025 to May 2025, we collected data from 221 elderly COPD patients. The mean age was 71 (65-77) years, Males accounted for a higher proportion than females. The mean NLR was 3,3 (2,2 – 6,2), CRP (mg/L)  4,3 (2,6 - 9,5), NLR showed a weak but statistically significant negative correlation with FEV1 (r = -0.147, p < 0,029) and a statistically significant positive correlation with CRP (r = 0,5012, p < 0,0001). Our study demonstrates that NLR is weakly but significantly inversely correlated with pulmonary function (FEV1), and positively correlated with CRP levels, indicating its potential role in assessing disease severity and inflammatory status.

Ye Cui, Xinqian Du, Yunqi Li et al.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by persistent inflammation and oxidative stress, which ultimately leads to progressive restriction of airflow. Extensive research findings have cogently suggested that the dysregulation of essential transition metal ions, notably iron, copper, and zinc, stands as a critical nexus in the perpetuation of inflammatory processes and oxidative damage within the lungs of COPD patients. Unraveling the intricate interplay between metal homeostasis, oxidative stress, and inflammatory signaling is of paramount importance in unraveling the intricacies of COPD pathogenesis. This comprehensive review aims to examine the current literature on the sources, regulation, and mechanisms by which metal dyshomeostasis contributes to COPD progression. We specifically focus on iron, copper, and zinc, given their well-characterized roles in orchestrating cytokine production, immune cell function, antioxidant depletion, and matrix remodeling. Despite the limited number of clinical trials investigating metal modulation in COPD, the advent of emerging methodologies tailored to monitor metal fluxes and gauge responses to chelation and supplementation hold great promise in unlocking the potential of metal-based interventions. We conclude that targeted restoration of metal homeostasis represents a promising frontier for ameliorating pathological processes driving COPD progression.

Rongjun Wan, Prakhyath Srikaram, Shaobing Xie et al.

Abstract Background Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence. Methods Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. Similar analyses were carried out in an independent cohort study Immune Mechanisms Severe Asthma (IMSA), which included bulk RNA-Seq and CyTOF data from bronchoalveolar lavage fluid (BALF) samples. Results The analysis of the scRNA-Seq data revealed that monocytes/ macrophages were the predominant cell type in the lung tissues of ACO patients, constituting more than 50% of the cells analyzed. Lung monocytes/macrophages from patients with ACO exhibited a lower prevalence of senescence as defined by lower enrichment scores of SenMayo and expression levels of cellular senescence markers. Intriguingly, analysis of the IMSA dataset showed similar results in patients with severe asthma. They also exhibited a lower prevalence of senescence, particularly in airway CD206 + macrophages, along with increased cytokine expression (e.g., IL-4, IL-13, and IL-22). Further exploration identified alveolar macrophages as a major subtype of monocytes/macrophages driving cellular senescence in ACO. Differentially expressed genes related to oxidation-reduction, cytokines, and growth factors were implicated in regulating senescence in alveolar macrophages. PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) emerged as one of the predominant regulators modulating the senescent signature of alveolar macrophages in ACO. Conclusion The findings suggest that senescence in macrophages, particularly alveolar macrophages, plays a crucial role in the pathophysiology of ACO. Furthermore, PPARγ may represent a potential therapeutic target for interventions aimed at modulating senescence-associated processes in ACO.Key words ACO, Asthma, COPD, Macrophages, Senescence, PPARγ.

, Najma Siddiqi, Josefien van Olmen et al.

Introduction The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs.Methods To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. Registration: https://www.comet-initiative.org/Studies/Details/1580.Results The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life.Conclusion Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs.PROSPERO registration number CRD42020197293.

Xuanzhong Chen, Xiaohao Mao, Qihan Guo et al.

Generalist Large Language Models (LLMs), such as GPT-4, have shown considerable promise in various domains, including medical diagnosis. Rare diseases, affecting approximately 300 million people worldwide, often have unsatisfactory clinical diagnosis rates primarily due to a lack of experienced physicians and the complexity of differentiating among many rare diseases. In this context, recent news such as "ChatGPT correctly diagnosed a 4-year-old's rare disease after 17 doctors failed" underscore LLMs' potential, yet underexplored, role in clinically diagnosing rare diseases. To bridge this research gap, we introduce RareBench, a pioneering benchmark designed to systematically evaluate the capabilities of LLMs on 4 critical dimensions within the realm of rare diseases. Meanwhile, we have compiled the largest open-source dataset on rare disease patients, establishing a benchmark for future studies in this domain. To facilitate differential diagnosis of rare diseases, we develop a dynamic few-shot prompt methodology, leveraging a comprehensive rare disease knowledge graph synthesized from multiple knowledge bases, significantly enhancing LLMs' diagnostic performance. Moreover, we present an exhaustive comparative study of GPT-4's diagnostic capabilities against those of specialist physicians. Our experimental findings underscore the promising potential of integrating LLMs into the clinical diagnostic process for rare diseases. This paves the way for exciting possibilities in future advancements in this field.

Nikita Kuzmin, Hieu-Thi Luong, Jixun Yao et al.

In this work, we describe our submissions for the Voice Privacy Challenge 2024. Rather than proposing a novel speech anonymization system, we enhance the provided baselines to meet all required conditions and improve evaluated metrics. Specifically, we implement emotion embedding and experiment with WavLM and ECAPA2 speaker embedders for the B3 baseline. Additionally, we compare different speaker and prosody anonymization techniques. Furthermore, we introduce Mean Reversion F0 for B5, which helps to enhance privacy without a loss in utility. Finally, we explore disentanglement models, namely $β$-VAE and NaturalSpeech3 FACodec.