bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of gestational age and birthweight with blood pressure, cardiac structure, and function in 4 years old: a prospective birth cohort study
Authors: Du Bowen , Wang Hualin , Wu Yujian , Li Zhuoyan , Niu Yiwei , Wang Qianchuo , Zhang Lin , Chen Sun , Wu Yurong , Huang Jihong , Sun Kun , Wang Jian 
Published: March 2023

Abstract
Background
Current evidence relating birthweight and gestational age to cardiovascular risk is conflicting. Whether these factors have independent or interactive impacts on cardiovascular parameters during early childhood remains unclear. The goal of this study was to explore whether there were any independent and interactive effects of gestational age and birthweight on blood pressure, left ventricle (LV) structure, and function in 4 years old.

Methods
This study included 1194 children in the Shanghai Birth Cohort from 2013 to 2016. Information about the mothers and children was recorded at time of birth using a questionnaire. Follow-up measurements, including anthropometric, blood pressure, and echocardiography, were taken between 2018 and 2021, when the children were 4 years old. Multiple linear or logistic regressions and restricted cubic spline were used to explore the association of birthweight and gestational age with cardiovascular measurements.

Results
Gestational age had a significant negative correlation with both systolic blood pressure [β =  − 0.41, 95% CI: (− 0.76, − 0.07)] and mean arterial pressure [β =  − 0.36, 95%CI: (− 0.66, − 0.07)]. The risk of prehypertension decreased with increased gestational age [OR = 0.54, 95% CI: (0.32, 0.93)]. The relationship between birthweight with blood pressure was U-shape (P for non-linear < 0.001). The wall thickness, volume, mass, and cardiac output of LV increased with birthweight, though the ejection fraction [β =  − 1.02, 95% CI: (− 1.76, − 0.27)] and shorten fraction [β = 0.72, 95% CI: (− 1.31, − 0.14)] decreased with birthweight. The risk of LV hypertrophy was not associated with birthweight [OR = 1.59, 95% CI: (0.68, 3.73)].

Conclusions
In this study, we found different associations of birthweight and gestational age with cardiovascular measurements in the offspring at 4 years old. Gestational age influenced blood pressure independent of birthweight. Heart size and function at 4 years old was influenced mostly by birthweight and not by gestational age.
Safety, tolerability, pharmacokinetics, and antiviral activity of the novel core protein allosteric modulator ZM-H1505R (Canocapavir) in chronic hepatitis B patients: a randomized multiple-dose escalation trial
Authors: Jia Haiyan , Mai Jiajia , Wu Min , Chen Hong , Li Xiaojiao , Li Cuiyun , Liu Jingrui , Liu Chengjiao , Hu Yue , Zhu Xiaoxue , Jiang Xiuhong , Hua Bo , Xia Tian , Liu Gang , Deng Aiyun , Liang Bo , Guo Ruoling , Lu Hui , Wang Zhe , Chen Huanming , Zhang Zhijun , Zhang Hong , Niu Junqi , Ding Yanhua 
Published: March 2023

Abstract
Background
Hepatitis B virus (HBV) core protein-targeting antivirals (CpTAs) are promising therapeutic agents for treating chronic hepatitis B (CHB). In this study, the antiviral activity, pharmacokinetics (PK), and tolerability of ZM-H1505R (Canocapavir), a chemically unique HBV CpTA, were evaluated in patients with CHB.

Methods
This study was a double-blind, randomized, placebo-controlled phase 1b trial in Chinese CHB patients. Noncirrhotic and treatment-naive CHB patients were divided into three cohorts (10 patients per cohort) and randomized within each cohort in a ratio of 4:1 to receive a single dose of 50, 100, or 200 mg of Canocapavir or placebo once a day for 28 consecutive days.

Results
Canocapavir was well tolerated, with the majority of adverse reactions being grade I or II in severity. There were no serious adverse events, and no patients withdrew from the study. Corresponding to 50, 100, and 200 mg doses of Canocapavir, the mean plasma trough concentrations of the drug were 2.7-, 7.0-, and 14.6-fold of its protein-binding adjusted HBV DNA EC50 (135 ng/mL), respectively, with linear PK and a low-to-mild accumulation rate (1.26–1.99). After 28 days of treatment, the mean maximum HBV DNA declines from baseline were -1.54, -2.50, -2.75, and -0.47 log10 IU/mL for the 50, 100, and 200 mg of Canocapavir or placebo groups, respectively; and the mean maximum pregenomic RNA declines from baseline were -1.53, -2.35, -2.34, and -0.17 log10 copies/mL, respectively.

Conclusions
Canocapavir treatment is tolerated with efficacious antiviral activity in CHB patients, supporting its further development in treating HBV infection.

Trial registration
ClinicalTrials.gov, number NCT05470829).
Life expectancy among older adults with or without frailty in China: multistate modelling of a national longitudinal cohort study
Authors: Gao Junling , Wang Yujie , Xu Jixiang , Jiang Junjia , Yang Shitong , Xiao Qianyi 
Published: March 2023

Abstract
Background
Little is known about life expectancy (LE) with or without frailty. We aimed to estimate the total LE and duration of the state of frailty in China.

Methods
This study included older adults aged 65 years and older from the Chinese Longitudinal Healthy Longevity Study (CLHLS). Frailty status was classified into robust, pre-frailty and frailty based on a cumulative deficit model. Total and specific frailty state LEs at 65 years of age were estimated and stratified by demographic characteristics, behaviours, and psychosocial factors using continuous-time multistate modelling.

Results
The total LE of older adults aged 65 years in China was 14.74 years on average (95% CI: 14.52–14.94), of which 4.18 years (95% CI: 4.05–4.30) were robust, 7.46 years (95% CI: 7.31–7.61) pre-frail and 3.10 years (95% CI: 3.01–3.20) frail. Older adults with higher robust LE included men (4.71 years, 95% CI: 4.56–4.88), married older adults (4.41 years, 95% CI: 4.27–4.56), those engaging in physical activity (4.41 years, 95% CI: 4.23–4.59), those consuming fruits daily (4.48 years, 95% CI: 4.22–4.77) and those with high social participation (4.39 years, 95% CI: 4.26–4.53). Increased educational attainment were gradually associated with increased robust LE.

Conclusions
Frailty may lead to a reduced total LE and robust LE of older adults in China. In addition to finding inequalities in total and robust LEs by socioeconomic status, our findings also highlight that healthy behaviours and social participation may ease frailty-related reductions in total and robust LE. Our findings imply that national life-course strategies aimed at frailty screening and psychosocial and behavioural interventions could be important for health aging in China.
Identification of potential ferroptosis hub genes in acute-on-chronic liver failure based on bioinformatics analysis and experimental verification
Authors: Kuang Meixia , Cai Longhui , Zhao Jing , Huang Liqiao , Ji Yichun , Lv Bingyao , Kuang Weihong 
Published: March 2023

Abstract
Background
Ferroptosis plays an important role in the development of acute-on-chronic liver failure (ACLF). The present project aimed to identify and validate the potential ferroptosis-related genes in ACLF by bioinformatics analysis and experimental verification.

Materials and methods
The GSE139602 dataset was obtained from the Gene Expression Omnibus database and intersected with ferroptosis genes. Ferroptosis-related differentially expressed genes (DEGs) between the ACLF tissue and healthy group were analyzed using bioinformatics methods. Analysis of enrichment, protein‒protein interactions, and hub genes was conducted. Potential drugs targeting these hub genes were retrieved from the DrugBank database. Finally, we performed real-time quantitative PCR (RT-qPCR) to validate the expression of the hub genes.

Results
A total of 35 ferroptosis-related DEGs were screened, which were enriched in the biosynthesis of amino acids, peroxisomes, fluid shear stress and atherosclerosis. PPI network analysis indicated five ferroptosis-related hub genes, namely, HRAS, TXNRD1, NQO1, PSAT1, and SQSTM1. The experimental validation indicated that the expression levels of HRAS, TXNRD1, NQO1, and SQSTM1 were lower, while the expression level of PSAT1 was higher in ACLF model rats than in healthy rats.

Conclusions
Our findings reveal that PSAT1, TXNRD1, HRAS, SQSTM1 and NQO1 may affect the development of ACLF by regulating ferroptotic events. These results provide a valid reference for potential mechanisms and identification in ACLF.
A retrospective analysis of MS/MS screening for IEM in high-risk areas
Authors: He Xiao , Kuang Juan , Lai Jiahong , Huang Jingxiong , Wang Yijin , Lan Guofeng , Xie Yingjun , Shi Xuekai 
Published: March 2023

AbstractInborn errors of metabolism (IEM) can lead to severe motor and neurological developmental disorders and even disability and death in children due to untimely treatment. In this study, we used tandem mass spectrometry (MS/MS) for primary screening and recall of those with positive primary screening for rescreening. Further diagnosis was based on biochemical tests, imaging and clinical presentation as well as accurate genetic testing using multi-gene panel with high-throughput sequencing of 130 IEM-related genes. The screening population was 16,207 newborns born between July 1, 2019, and December 31, 2021. Based on the results, 8 newborns were diagnosed with IEM, constituting a detection rate of 1:2,026. Phenylketonuria was the most common form of IEM. In addition, seven genes associated with IEM were detected in these eight patients. All eight patients received standardized treatment starting in the neonatal period, and the follow-up results showed good growth and development. Therefore, our study suggests that MS/MS rescreening for IEM pathogenic variants in high-risk areas, combined with a sequencing validation strategy, can be highly effective in the early detection of affected children. This strategy, combined with early intervention, can be effective in preventing neonatal morbidity and improving population quality.
The emerging role of the piRNA/PIWI complex in respiratory tract diseases
Authors: Yao Yizhu , Li Yaozhe , Zhu Xiayan , Zhao Chengguang , Yang Lehe , Huang Xiaoying , Wang Liangxing 
Published: March 2023

AbstractPIWI-interacting RNA (piRNA) is a class of recently discovered small non-coding RNA molecules with a length of 18–33 nt that interacts with the PIWI protein to form the piRNA/PIWI complex. The PIWI family is a subfamily of Argonaute (AGO) proteins that also contain the AGO family which bind to microRNA (miRNA). Recently studies indicate that piRNAs are not specific to in the mammalian germline, they are also expressed in a tissue-specific manner in a variety of human tissues and participated in various of diseases, such as cardiovascular, neurological, and urinary tract diseases, and are especially prevalent in malignant tumors in these systems. However, the functions and abnormal expression of piRNAs in respiratory tract diseases and their underlying mechanisms remain incompletely understood. In this review, we discuss current studies summarizing the biogenetic processes, functions, and emerging roles of piRNAs in respiratory tract diseases, providing a reference value for future piRNA research.
Weight loss and outcomes in subjects with progressive pulmonary fibrosis: data from the INBUILD trial
Authors: Kreuter Michael , Bendstrup Elisabeth , Jouneau Stéphane , Maher Toby M. , Inoue Yoshikazu , Miede Corinna , Lievens Dirk , Crestani Bruno 
Published: March 2023

Abstract
Background
Lower body mass index (BMI) and weight loss have been associated with worse outcomes in some studies in patients with pulmonary fibrosis. We analyzed outcomes in subgroups by BMI at baseline and associations between weight change and outcomes in subjects with progressive pulmonary fibrosis (PPF) in the INBUILD trial.

Methods
Subjects with PPF other than idiopathic pulmonary fibrosis were randomized to receive nintedanib or placebo. In subgroups by BMI at baseline (< 25, ≥ 25 to < 30, ≥ 30 kg/m2), we analyzed the rate of decline in FVC (mL/year) over 52 weeks and time-to-event endpoints indicating disease progression over the whole trial. We used a joint modelling approach to assess associations between change in weight and the time-to-event endpoints.

Results
Among 662 subjects, 28.4%, 36.6% and 35.0% had BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively. The rate of decline in FVC over 52 weeks was numerically greater in subjects with baseline BMI < 25 than ≥ 25 to < 30 or ≥ 30 kg/m2 (nintedanib: − 123.4, − 83.3, − 46.9 mL/year, respectively; placebo: − 229.5; − 176.9; − 171.2 mL/year, respectively). No heterogeneity was detected in the effect of nintedanib on reducing the rate of FVC decline among these subgroups (interaction p = 0.83). In the placebo group, in subjects with baseline BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively, 24.5%, 21.4% and 14.0% of subjects had an acute exacerbation or died, and 60.2%, 54.5% and 50.4% of subjects had ILD progression (absolute decline in FVC % predicted ≥ 10%) or died over the whole trial. The proportions of subjects with these events were similar or lower in subjects who received nintedanib versus placebo across the subgroups. Based on a joint modelling approach, over the whole trial, a 4 kg weight decrease corresponded to a 1.38-fold (95% CI 1.13, 1.68) increase in the risk of acute exacerbation or death. No association was detected between weight loss and the risk of ILD progression or the risk of ILD progression or death.

Conclusions
In patients with PPF, lower BMI at baseline and weight loss may be associated with worse outcomes and measures to prevent weight loss may be required.
Trial registration:https://clinicaltrials.gov/ct2/show/NCT02999178.
Surface electromyography to quantify neuro-respiratory drive and neuro-mechanical coupling in mechanically ventilated children
Authors: Koopman Alette A. , van Dijk Jefta , Oppersma Eline , Blokpoel Robert G. T. , Kneyber Martin C. J. 
Published: March 2023

Abstract
Background
The patient’s neuro-respiratory drive, measured as electrical activity of the diaphragm (EAdi), quantifies the mechanical load on the respiratory muscles. It correlates with respiratory effort but requires a dedicated esophageal catheter. Transcutaneous (surface) monitoring of respiratory muscle electromyographic (sEMG) signals may be considered a suitable alternative to EAdi because of its non-invasive character, with the additional benefit that it allows for simultaneously monitoring of other respiratory muscles. We therefore sought to study the neuro-respiratory drive and timing of inspiratory muscles using sEMG in a cohort of children enrolled in a pediatric ventilation liberation trial. The neuro-mechanical coupling, relating the pressure generated by the inspiratory muscles to the sEMG signals of these muscles, was also calculated.

Methods
This is a secondary analysis of data from a randomized cross-over trial in ventilated patients aged < 5 years. sEMG recordings of the diaphragm and parasternal intercostal muscles (ICM), esophageal pressure tracings and ventilator scalars were simultaneously recorded during continuous spontaneous ventilation and pressure controlled-intermittent mandatory ventilation, and at three levels of pressure support. Neuro-respiratory drive, timing of diaphragm and ICM relative to the mechanical ventilator’s inspiration and neuro-mechanical coupling were quantified.

Results
Twenty-nine patients were included (median age: 5.9 months). In response to decreasing pressure support, both amplitude of sEMG (diaphragm: p = 0.001 and ICM: p = 0.002) and neuro-mechanical efficiency indices increased (diaphragm: p = 0.05 and ICM: p < 0.001). Poor correlations between neuro-respiratory drive and respiratory effort were found, with R2: 0.088 [0.021–0.152].

Conclusions
sEMG allows for the quantification of the electrical activity of the diaphragm and ICM in mechanically ventilated children. Both neuro-respiratory drive and neuro-mechanical efficiency increased in response to lower inspiratory assistance. There was poor correlation between neuro-respiratory drive and respiratory effort.

Trial registration

ClinicalTrials.gov ID NCT05254691. Registered 24 February 2022, registered retrospectively.
Particulate matter10-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression
Authors: Choi Yong Jun , Han Heejae , Lee Jae-Hyun , Lee Jaeuk , Kim Chi Young , Byun Min Kwang , Cho Jae Hwa , Park Hye Jung 
Published: March 2023

Abstract
Background
Particulate matter10 (PM10) can induce airway inflammation and fibrosis. Recently, chitinase-1 has been shown to play key roles in inflammation and fibrosis. We aimed to investigate the effects of chitinase-1 inhibitor in PM10-treated murine mice models.

Methods
In female BALB/c mice, PM10 was intranasally administered six times over 3 weeks, and ovalbumin (OVA) was intraperitoneally injected and then intranasally administered. Chitinase-1 inhibitor (CPX) 6 times over 3 weeks or dexamethasone 3 times in the last week were intraperitoneally administered. Two days after the last challenges, mice were euthanized. Messenger RNA sequencing using lung homogenates was conducted to evaluate signaling pathways.

Results
PM10 and/or OVA-induced airway inflammation and fibrosis murine models were established. CPX and dexamethasone ameliorated PM10 or PM10/OVA-induced airway hyper-responsiveness, airway inflammation, and fibrosis. CPX and dexamethasone also reduced levels of various inflammatory markers in lung homogenates. PM10 and OVA also induced changes in mRNA expression across an extreme range of genes. CPX and dexamethasone decreased levels of mRNA expression especially associated with inflammation and immune regulation. They also significantly regulated asthma and asthma-related pathways, including the JACK-STAT signaling pathway.

Conclusions
Chitinase-1 suppression by CPX can regulate PM10- and OVA-induced and aggravated airway inflammation and fibrosis via an asthma-related signaling pathway.
General versus central adiposity as risk factors for cardiovascular-related outcomes in a high-risk population with type 2 diabetes: a post hoc analysis of the REWIND trial
Authors: Franek Edward , Pais Prem , Basile Jan , Nicolay Claudia , Raha Sohini , Hickey Ana , Ahmad Nadia N. , Konig Manige , Kan Hong , Gerstein Hertzel C. 
Published: March 2023

AbstractBackgroundIn clinical practice, anthropometric measures other than BMI are rarely assessed yet may be more predictive of cardiovascular (CV) risk. We analyzed the placebo group of the REWIND CV Outcomes Trial to compare several anthropometric measures as baseline risk factors for cardiovascular disease (CVD)-related outcomes in participants with type 2 diabetes (T2D).MethodsData from the REWIND trial placebo group (N = 4952) were analyzed. All participants had T2D, age ≥ 50 years, had either a previous CV event or CV risk factors, and a BMI of ≥ 23 kg/m2. Cox proportional hazard models were used to investigate if BMI, waist-to-hip ratio (WHR), and waist circumference (WC) were significant risk factors for major adverse CV events (MACE)-3, CVD-related mortality, all-cause mortality, and heart failure (HF) requiring hospitalization. Models were adjusted for age, sex, and additional baseline factors selected by LASSO method. Results are presented for one standard deviation increase of the respective anthropometric factor.ResultsParticipants in the placebo group experienced 663 MACE-3 events, 346 CVD-related deaths, 592 all-cause deaths, and 226 events of HF requiring hospitalization during the median follow-up of 5.4 years. WHR and WC, but not BMI, were identified as independent risk factors of MACE-3 (hazard ratio [HR] for WHR: 1.11 [95% CI 1.03 to 1.21]; p = 0.009; HR for WC: 1.12 [95% CI 1.02 to 1.22]; p = 0.012). WC adjusted for hip circumference (HC) showed the strongest association with MACE-3 compared to WHR, WC, or BMI unadjusted for each other (HR: 1.26 [95% CI 1.09 to 1.46]; p = 0.002). Results for CVD-related mortality and all-cause mortality were similar. WC and BMI were risk factors for HF requiring hospitalization, but not WHR or WC adjusted for HC (HR for WC: 1.34 [95% CI 1.16 to 1.54]; p < 0.001; HR for BMI: 1.33 [95% CI 1.17 to 1.50]; p < 0.001). No significant interaction with sex was observed.ConclusionsIn this post hoc analysis of the REWIND placebo group, WHR, WC and/or WC adjusted for HC were risk factors for MACE-3, CVD-related mortality, and all-cause mortality; while BMI was only a risk factor for HF requiring hospitalization. These findings indicate the need for anthropometric measures that consider body fat distribution when assessing CV risk.
Adherence to antidiabetic drug therapy and reduction of fatal events in elderly frail patients
Authors: Rea Federico , Savaré Laura , Valsassina Valeria , Ciardullo Stefano , Perseghin Gianluca , Corrao Giovanni , Mancia Giuseppe 
Published: March 2023

Abstract
Background
To evaluate the protective effect of oral antidiabetic drugs in a large cohort of elderly patients with type 2 diabetes differing for age, clinical status, and life expectancy, including patients with multiple comorbidities and short survival.

Methods
A nested case–control study was carried out by including the cohort of 188,983 patients from Lombardy (Italy), aged ≥ 65 years, who received ≥ 3 consecutive prescriptions of antidiabetic agents (mostly metformin and other older conventional agents) during 2012. Cases were the 49,201 patients who died for any cause during follow-up (up to 2018). A control was randomly selected for each case. Adherence to drug therapy was measured by considering the proportion of days of the follow-up covered by the drug prescriptions. Conditional logistic regression was used to model the risk of outcome associated with adherence to antidiabetic drugs. The analysis was stratified according to four categories of the clinical status (good, intermediate, poor, and very poor) differing for life expectancy.

Results
There was a steep increase in comorbidities and a marked reduction of the 6-year survival from the very good to the very poor (or frail) clinical category. Progressive increase in adherence to treatment was associated with a progressive decrease in the risk of all-cause mortality in all clinical categories and at all ages (65–74, 75–84 and ≥ 85 years) except for the frail patient subgroup aged ≥ 85 years. The mortality reduction from lowest to highest adherence level showed a tendency to be lower in frail patients compared to the other categories. Similar although less consistent results were obtained for cardiovascular mortality.

Conclusions
In elderly diabetic patients, increased adherence to antidiabetic drugs is associated with a reduction in the risk of mortality regardless of the patients’ clinical status and age, with the exception of very old patients (age ≥ 85 years) in the very poor or frail clinical category. However, in the frail patient category the benefit of treatment appears to be less than in patients in good clinical conditions.