bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of mepolizumab in a Chinese population with severe asthma: a phase III, randomised, double-blind, placebo-controlled trial
Authors: Chen Ruchong , Wei Liping , Dai Yuanrong , Wang Zaiyi , Yang Danrong , Jin Meiling , Xiong Cui , Li Ting , Hu Shuling , Song Jie , Chan Robert , Kumar Subramanya , Abdelkarim Azza , Zhong Nanshan 
Published: February 2024

BackgroundIn China, the prevalence of severe asthma with eosinophilic phenotype is rising, yet treatment options are limited. Mepolizumab is the first targeted biologic therapy for eosinophilic-driven disease in China. This study (clinicaltrials.gov identifierNCT03562195) evaluated efficacy and safety of mepolizumab in Chinese patients with severe asthma.MethodsThe phase III, multicentre, randomised, placebo-controlled, double-blind, parallel-group study enrolled patients aged ≥12 years with severe asthma, with two or more exacerbations in the previous year, and on inhaled corticosteroids plus at least one controller medication. Following a 1–4-week run-in, patients were randomised 1:1 to mepolizumab 100 mg or placebo subcutaneously every 4 weeks for 52 weeks. The primary end-point was annualised rate of clinically significant exacerbations (CSEs) through week 52. Secondary end-points were time to first CSE, frequency of CSEs requiring hospitalisation/emergency department visits or hospitalisation over 52 weeks, mean change in St George's Respiratory Questionnaire (SGRQ) total score and pre-bronchodilator forced expiratory volume in 1 s (FEV1) at week 52; safety was evaluated.ResultsThe modified intention-to-treat population included 300 patients. At week 52 with mepolizumabversusplacebo, annualised rate of CSEs was 65% lower (0.45versus1.31 events per year; rate ratio 0.35, 95% CI 0.24–0.50; p<0.001); time to first CSE longer (hazard ratio 0.38, 95% CI 0.26–0.56; p<0.001) and number of CSEs requiring hospitalisation/emergency department visit lower (rate ratio 0.30, 95% CI 0.12–0.77; p=0.012). From baseline to week 52, SGRQ score improved (p=0.001) and pre-bronchodilator FEV1increased (p=0.006). Incidence of adverse events was similar between treatment groups.ConclusionMepolizumab provided clinical benefits to patients with severe asthma in China and showed a favourable benefit–risk profile.
COPD Assessment Test and risk of readmission in patients with bronchiectasis: a prospective cohort study
Authors: Wang Juan , Chen Xiaoting , He Siqi , Li Jing , Ma Tianyuan , Liu Lu , Zhang Lei , Bu Xiaoning 
Published: February 2024

IntroductionReadmission following bronchiectasis exacerbation is a common and challenging clinical problem and few simple predictive tools exist. The COPD Assessment Test (CAT) is an easy-to-use questionnaire. This study aims to evaluate the predictive value of CAT scores in determining the risk of readmission in patients with bronchiectasis exacerbation.MethodsWe conducted a prospective cohort study in 106 bronchiectasis patients admitted with exacerbation. All patients completed the CAT at admission and at discharge. Patients were followed-up for 12 months to collect data on readmission. The area under the curve was used to measure the predictive value of CAT at admission, CAT at discharge and change in CAT for readmission due to bronchiectasis exacerbation.Results46 patients were readmitted for bronchiectasis exacerbation within 12 months. High CAT at admission was an independent risk factor for readmission within 12 months in patients with acute exacerbation of bronchiectasis (hazard ratio 3.201, 95% CI 1.065–9.624; p<0.038) after adjustment for confounding variables. The cut-off value of CAT at admission and CAT at discharge to predict 12-month readmission in patients with acute exacerbation of bronchiectasis was 23.5 (sensitivity 62.2%, specificity 83.6%) and 15.5 (sensitivity 52.2%, specificity 87.0%).ConclusionsCAT at admission is a strong predictor of readmission in patients with bronchiectasis exacerbation.
Surveillance of the respiratory syncytial virus outside infancy: impact of testing methods, a retrospective observational study
Authors: Yin Nicolas , Van den Wijngaert Sigi , Wautier Magali , Martiny Delphine , Hallin Marie , Vandenberg Olivier 
Published: February 2024

BackgroundThe European Medicines Agency has approved several vaccines to protect the elderly against respiratory syncytial virus (RSV) infections. However, differences in performance between antigen and PCR tests, especially in adults, can make monitoring RSV difficult. This study aims to assess the impact of the chosen diagnostic methods on the surveillance of RSV.MethodsRSV and influenza test results obtained from July 2022 to June 2023 in a consolidated clinical laboratory in Brussels, Belgium, were collected. These results included antigen tests, quadruplex PCR tests and viral cultures on respiratory samples. Epidemiological trends related to the age of patients and the diagnostic methods were analysed.ResultsAmong 14 761 RSV tests, the overall number of positive tests for infants until 1 year of age peaked on 5 November 2022 (67 per 7 days) whereas it peaked on 22 December 2022 for adults (33 per 7 days). Positive antigen tests peaked on 7 November 2022 (56 per 7 days) whereas positive PCRs peaked on 19 December 2022 (36 per 7 days). Nevertheless, the positivity rate of RSV PCRs had peaked 1 month previously. Infants were mainly diagnosed through antigen testing, contrary to older patients. The influenza epidemic was probably the cause of the increased use of a quadruplex PCR, leading to a delayed increase in the absolute number of PCRs positive for RSV.ConclusionThis study shows that the use of different diagnostic methods could lead to an erroneous representation of RSV epidemiology in adults due to the lack of sensitivity of antigen detection. RSV surveillance in the elderly should rely rather on molecular methods.
The role of GPR81–cAMP–PKA pathway in endurance training-induced intramuscular triglyceride accumulation and mitochondrial content changes in rats
Authors: Li Lin , Lai Xiangdeng , Ni Yihan , Chen Siyu , Qu Yaqian , Hu Zhiqiang , Sun Jingquan 
Published: February 2024

AbstractThe athlete's paradox phenomenon involves the accumulation of intramuscular triglycerides (IMTG) in both insulin-resistant and insulin-sensitive endurance athletes. Nevertheless, a complete understanding of this phenomenon is yet to be achieved. Recent research indicates that lactate, a common byproduct of physical activity, may increase the accumulation of IMTG in skeletal muscle. This is achieved through the activation of G protein-coupled receptor 81 (GPR81) leads to the suppression of the cyclic adenosine monophosphate–protein kinase A (cAMP–PKA) pathway. The mechanism accountable for the increase in mitochondrial content in skeletal muscle triggered by lactate remains incomprehensible. Based on current research, our objective is to explore the role of the GPR81-inhibited cAMP–PKA pathway in the aggregation of IMTG and the increase in mitochondrial content as a result of prolonged exercise. The GPR81–cAMP–PKA-signaling pathway regulates the buildup of IMTG caused by extended periods of endurance training (ET). This is likely due to a decrease in proteins related to fat breakdown and an increase in proteins responsible for fat production. It is possible that the GPR81–cAMP–PKA pathway does not contribute to the long-term increase in mitochondrial biogenesis and content, which is induced by chronic ET. Additional investigation is required to explore the possible hindrance of the mitochondrial biogenesis and content process during physical activity by the GPR81–cAMP–PKA signal.
Thermal gradient ring for analysis of temperature-dependent behaviors involving TRP channels in mice
Authors: Ujisawa Tomoyo , Lei Jing , Kashio Makiko , Tominaga Makoto 
Published: February 2024

AbstractThere are a lot of temperature-sensitive proteins including transient receptor potential (TRP) channels. Some TRP channels are temperature receptors having specific activation temperatures in vitro that are within the physiological temperature range. Mice deficient in specific TRP channels show abnormal thermal behaviors, but the role of TRP channels in these behaviors is not fully understood. The Thermal Gradient Ring is a new apparatus that allows mice to freely move around the ring floor and not stay in a corner. The system can analyze various factors (e.g., ‘Spent time’, ‘Travel distance’, ‘Moving speed’, ‘Acceleration’) associated with temperature-dependent behaviors of TRP-deficient mice. For example, the Ring system clearly discriminated differences in temperature-dependent phenotypes between mice with diabetic peripheral neuropathy and TRPV1−/− mice, and demonstrated the importance of TRPV3 in temperature detection in skin. Studies using the Thermal Gradient Ring system can increase understanding of the molecular basis of thermal behaviors in mice and in turn help develop strategies to affect responses to different temperature conditions in humans.
A novel isatin Schiff based cerium complex: synthesis, characterization, antimicrobial activity and molecular docking studies
Authors: Saad Heba E. , El-Reash Gaber M. Abu , gaber Mohamed , Hashem Mohamed A. , El-Reash Yasmeen G. Abou , Elamin Nuha Y. , Elamin Mohamed R. , El-Sayed Yusif S. 
Published: February 2024

AbstractIn this work, a novel isatin-Schiff base L2 had been synthesized through a simple reaction between isatin and 2-amino-5-methylthio-1,3,4-thiadiazole. The produced Schiff base L2 was then subjected to a hydrothermal reaction with cerium chloride to produce the cerium (III)-Schiff base complex C2. Several spectroscopic methods, including mass spectra, FT-IR, elemental analysis, UV–vis, 13C-NMR, 1H-NMR, Thermogravimetric Analysis, HR-TEM, and FE-SEM/EDX, were used to completely characterize the produced L2 and C2. A computer simulation was performed using the MOE software program to find out the probable biological resistance of studied compounds against the proteins in some types of bacteria or fungi. To investigate the interaction between the ligand and its complex, we conducted molecular docking simulations using the molecular operating environment (MOE). The docking simulation findings revealed that the complex displayed greater efficacy and demonstrated a stronger affinity for Avr2 effector protein from the fungal plant pathogen Fusarium oxysporum (code 5OD4) than the original ligand. The antibacterial activity of the ligand and its Ce3+ complex were applied in vitro tests against different microorganism. The study showed that the complex was found to be more effective than the ligand.
Genome-wide DNA N6-methyladenosine in Aeromonas veronii and Helicobacter pylori
Authors: Zhao Honghao , Ma Jiayue , Tang Yanqiong , Ma Xiang , Li Juanjuan , Li Hong , Liu Zhu 
Published: February 2024

Abstract
Background
DNA N6-methyladenosine (6mA), as an important epigenetic modification, widely exists in bacterial genomes and participates in the regulation of toxicity, antibiotic resistance, and antioxidant. With the continuous development of sequencing technology, more 6mA sites have been identified in bacterial genomes, but few studies have focused on the distribution characteristics of 6mA at the whole-genome level and its association with gene expression and function.

Results
This study conducted an in-depth analysis of the 6mA in the genomes of two pathogenic bacteria, Aeromonas veronii and Helicobacter pylori. The results showed that the 6mA was widely distributed in both strains. In A. veronii, 6mA sites were enriched at 3’ end of protein-coding genes, exhibiting a certain inhibitory effect on gene expression. Genes with low 6mA density were associated with cell motility. While in H. pylori, 6mA sites were enriched at 5’ end of protein-coding genes, potentially enhancing gene expression. Genes with low 6mA density were closely related to defense mechanism.

Conclusions
This study elucidated the distribution characteristics of 6mA in A. veronii and H. pylori, highlighting the effects of 6mA on gene expression and function. These findings provide valuable insights into the epigenetic regulation and functional characteristics of A. veronii and H. pylori.
Nomogram for predicting postoperative pulmonary complications in spinal tumor patients
Authors: Zou Jingcheng , Luo Ge , Zhou Liwang , Wang Xuena , Wang Tingting , Gao Qi , Lv Tao , Xu Guangxin , Yao Yuanyuan , Yan Min 
Published: February 2024

Abstract
Objectives
Although several independent risk factors for postoperative pulmonary complications (PPCs) after spinal tumor surgery have been studied, a simple and valid predictive model for PPC occurrence after spinal tumor surgery has not been developed.

Patients and methods
We collected data from patients who underwent elective spine surgery for a spinal tumor between 2013 and 2020 at a tertiary hospital in China. Data on patient characteristics, comorbidities, preoperative examinations, intraoperative variables, and clinical outcomes were collected. We used univariable and multivariable logistic regression models to assess predictors of PPCs and developed and validated a nomogram for PPCs. We evaluated the performance of the nomogram using the area under the receiver operating characteristic curve (ROC), calibration curves, the Brier Score, and the Hosmer–Lemeshow (H–L) goodness-of-fit test. For clinical use, decision curve analysis (DCA) was conducted to identify the model’s performance as a tool for supporting decision-making.

Results
Among the participants, 61 (12.4%) individuals developed PPCs. Clinically significant variables associated with PPCs after spinal tumor surgery included BMI, tumor location, blood transfusion, and the amount of blood lost. The nomogram incorporating these factors showed a concordance index (C-index) of 0.755 (95% CI: 0.688–0.822). On internal validation, bootstrapping with 1000 resamples yielded a bias-corrected area under the receiver operating characteristic curve of 0.733, indicating the satisfactory performance of the nomogram in predicting PPCs. The calibration curve demonstrated accurate predictions of observed values. The decision curve analysis (DCA) indicated a positive net benefit for the nomogram across most predicted threshold probabilities.

Conclusions
We have developed a new nomogram for predicting PPCs in patients who undergo spinal tumor surgery.
Multi-omics sequencing revealed endostar combined with cisplatin treated non small cell lung cancer via anti-angiogenesis
Authors: Wang Yufei , Ren Hong 
Published: February 2024

Abstract
Background
Endostar, an anti-angiogenic drug, has been approved for treating non-small cell lung cancer (NSCLC). At present, endostar combined with radiotherapy or chemotherapy has achieved ideal results in the treatment of some tumors, but there is a lack of application and study in NSCLC. This study investigated the therapeutic effect and potential mechanism of endostar combined with cisplatin (EC) in NSCLC.

Methods
HE staining, TUNEL staining, immunofluorescence, colony formation ability, and cell migration ability were used to evaluate the anti-tumor activity of EC. The expressions of FMOD, VEGF, FGF-2, and PDGF-B were detected by western blotting and qPCR. The target of combination therapy was analyzed by m6A sequencing and RNA sequencing. METTL3 knockdown and overexpressed A549 cells were constructed and co-cultured with HUVECs to further evaluate the effect of METLL3 on combination therapy.

Results
Combination therapy significantly reduced the colony formation and migration ability of NSCLC cells, induced cell apoptosis, and inhibited the tube formation ability of HUVECs. The results of m6A sequencing and RNA sequencing showed that the EC could down-regulate the expression level of FMOD in tumor tissues, which might be related to the reduction of its m6A methylation modification regulatory enzyme METTL3. Restricting FMOD expression could reduce the expression of FGF2, TGF-β1, VEGF and PDGF-B. Moreover, overexpression of METTLE almost abolished the anti-tumor effect of EC and promoted angiogenesis.

Conclusions
Endostar combined with cisplatin might exert anti-tumor effects by down-regulating the expression of METTL3 and FMOD.
Utilization, quality, and spending for pediatric Medicaid enrollees with primary care in health centers vs non-health centers
Authors: Volerman Anna , Carlson Bradley , Wan Wen , Murugesan Manoradhan , Asfour Nour , Bolton Joshua , Chin Marshall H. , Sripipatana Alek , Nocon Robert S. 
Published: February 2024

Abstract
Background
Limited research has explored the performance of health centers (HCs) compared to other primary care settings among children in the United States. We evaluated utilization, quality, and expenditures for pediatric Medicaid enrollees receiving care in HCs versus non-HCs.

Methods
This national cross-sectional study utilized 2012 Medicaid Analytic eXtract (MAX) claims to examine children 0–17 years with a primary care visit, stratified by whether majority (> 50%) of primary care visits were at HCs or non-HCs. Outcome measures include utilization (primary care visits, non-primary care outpatient visits, prescription claims, Emergency Department (ED) visits, hospitalizations) and quality (well-child visits, avoidable ED visits, avoidable hospitalizations). For children enrolled in fee-for-service Medicaid, we also measured expenditures. Propensity score-based overlap weighting was used to balance covariates.

Results
A total of 2,383,270 Medicaid-enrolled children received the majority of their primary care at HCs, while 18,540,743 did at non-HCs. In adjusted analyses, HC patients had 20% more primary care visits, 15% less non-primary care outpatient visits, and 21% less prescription claims than non-HC patients. ED visits were similar across the two groups, while HC patients had 7% lower chance of hospitalization than non-HC. Quality of care outcomes favored HC patients in main analyses, but results were less robust when excluding managed care beneficiaries. Total expenditures among the fee-for-service subpopulation were lower by $239 (8%) for HC patients.

Conclusions
In this study of nationwide claims data to evaluate healthcare utilization, quality, and spending among Medicaid-enrolled children who receive primary care at HCs versus non-HCs, findings suggest primary care delivery in HCs may be associated with a more cost-effective model of healthcare for children.
Examining the referral of patients with elevated blood pressure to health resources in an under-resourced community in South Africa
Authors: McNulty Lia K. , Stoutenberg Mark , Kolkenbeck-Ruh Andrea , Harrison Amy , Mmoledi Thabiso , Katiyo Daniel , Mhlaba Mimi , Kubheka Delisile , Ware Lisa J. 
Published: February 2024

Abstract
Background
Low-and-middle income countries face a disproportionate burden of non-communicable diseases (NCDs) that threaten to overwhelm under-resourced health systems. Community health workers (CHWs) can promote NCD prevention, reach patients, and connect them to local community health resources; however, little has been done to examine how referrals to these resources are utilized by community members. The purpose of this study is to examine the use of referrals to community-based health resources and investigate the factors influencing patient utilization of referrals connecting them to appropriate health resources for elevated blood pressure (BP).

Methods
CHWs conducted home visits, which included BP screening and brief counseling, with community members in Soweto, South Africa. Participants with elevated (systolic BP: 121–139/ diastolic BP: 81–89 mmHg) or high (≥ 140/90 mmHg) BP were referred to either a local, community-based physical activity (PA) program managed by a non-governmental organization or local health clinics. The number of participants that received and utilized their referrals was tracked. Follow-up interviews were conducted with individuals given a referral who: (1) went to the PA program, (2) did not go to the PA program, (3) went to a clinic, and (4) did not go to a clinic. Interviews were transcribed and analyzed to identify common themes and differences between groups regarding their decisions to utilize the referrals.

Results
CHWs visited 1056 homes, with 1001 community members consenting to the screening; 29.2% (n = 292) of adults were classified as having optimal BP (≤120/80 mmHg), 35.8% (n = 359) had elevated BP, and 35.0% (n = 350) had high BP. One hundred and seventy-three participants accepted a referral to the PA program with 46 (26.6%) enrolling. Five themes emerged from the interviews: (1) prior knowledge and thoughts on BP, (2) psychosocial factors associated with BP control, (3) perception about receiving the referral, (4) contextual factors influencing referral utilization, and (5) perceived benefits of utilizing the referral.

Conclusion
CHWs can successfully increase community members’ access to health resources by providing appropriate referrals. However, greater attention needs to address community members’ barriers and hesitancy to utilize health resources.
Association of social vulnerability index and masking adherence among children enrolled in COVID-19 community research partnership study
Authors: Dantuluri Keerti L. , Buahin Asare , Uschner Diane , DeWitt Michael E. , Rossman Whitney , Dunn Connell O. , Hetherington Timothy C. , Priem Jennifer , Castri Paola , Lagarde William H. , Gibbs Michael , Ahmed Amina ,   The COVID-19 Community Research Partnership
Published: February 2024

Abstract
Background
Individuals with high social vulnerability index (SVI) have poorer outcomes with COVID-19. Masking reduces transmission of COVID-19 among children, but how SVI plays a role in masking behavior is unknown. We aimed to measure the association of SVI with masking adherence among children during the COVID-19 pandemic.

Methods
We conducted a multi-site, prospective syndromic surveillance study among children aged 2 – 17 years in the Southeastern United States by daily electronic surveys which solicited symptoms of COVID-19-like illness, infection with or exposure to SARS-CoV-2, masking habits, and any receipt of COVID-19 vaccines. Parents/guardians submitted surveys for their children; adolescents 13 years and older could opt to submit their own surveys. Multivariable and univariate linear models were used to measure the associations of different predictors such as SVI with masking adherence.

Results
One thousand four hundred sixty-one children from 6 states and 55 counties predominately from North and South Carolina were included in the analysis. Most children in the cohort were 5 – 11 years old, non-Hispanic White, from urban counties, and with low-moderate SVI. Overall masking adherence decreased over time, and older children had higher masking adherence throughout the study period compared with younger children. Children who resided in urban counties had greater masking adherence throughout the study period than those who resided in suburban or rural counties. Masking adherence was higher among children with both low and medium SVI than those with high SVI.

Conclusions
Despite being at risk for more severe outcomes with COVID-19, children with high SVI had lower levels of masking adherence compared to those with low SVI. Our findings highlight opportunities for improved and targeted messaging in these vulnerable communities.