bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical immunogenicity and protective efficacy of a SARS-CoV-2 RBD-based vaccine produced with the thermophilic filamentous fungal expression system Thermothelomyces heterothallica C1
Authors: Gonzalez-Hernandez Mariana , Kaiser Franziska Karola , Steffen Imke , Ciurkiewicz Malgorzata , van Amerongen Geert , Tchelet Ronen , Emalfarb Mark , Saloheimo Markku , Wiebe Marilyn G. , Vitikainen Marika , Albulescu Irina C. , Bosch Berend-Jan , Baumgärtner Wolfgang , Haagmans Bart L. , Osterhaus Albert D. M. E. 
Published: June 2023

IntroductionThe emergency use of vaccines has been the most efficient way to control the coronavirus disease 19 (COVID-19) pandemic. However, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has reduced the efficacy of currently used vaccines. The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein is the main target for virus neutralizing (VN) antibodies.MethodsA SARS-CoV-2 RBD vaccine candidate was produced in the Thermothelomyces heterothallica (formerly, Myceliophthora thermophila) C1 protein expression system and coupled to a nanoparticle. Immunogenicity and efficacy of this vaccine candidate was tested using the Syrian golden hamster (Mesocricetus auratus) infection model.ResultsOne dose of 10-μg RBD vaccine based on SARS-CoV-2 Wuhan strain, coupled to a nanoparticle in combination with aluminum hydroxide as adjuvant, efficiently induced VN antibodies and reduced viral load and lung damage upon SARS-CoV-2 challenge infection. The VN antibodies neutralized SARS-CoV-2 variants of concern: D614G, Alpha, Beta, Gamma, and Delta.DiscussionOur results support the use of the Thermothelomyces heterothallica C1 protein expression system to produce recombinant vaccines against SARS-CoV-2 and other virus infections to help overcome limitations associated with the use of mammalian expression system.
Constipation in multiple system atrophy: a pilot study in Chinese patients
Authors: Chen Yalan , Huang Hongyan , Zhang Peng , Xu Yanming , Chen Yangmei 
Published: June 2023

ObjectiveThis study aimed to investigate the prevalence and clinical characteristics of subjective constipation in Chinese patients with multiple system atrophy (MSA), as well as the timing of constipation onset relative to the occurrence of motor symptoms.MethodsA total of 200 patients who were consecutively admitted to two large Chinese hospitals from February 2016 to June 2021 and subsequently diagnosed with probable MSA were enrolled in this cross-sectional study. Demographic and constipation-related clinical data were collected, and motor and non-motor symptoms were assessed using various scales and questionnaires. Subjective constipation was defined using ROME III criteria.ResultsThe frequency of constipation was 53.5, 59.7, and 39.3% in MSA, MSA with predominately parkinsonism (MSA-P), and MSA with predominately cerebellar ataxia (MSA-C), respectively. MSA-P subtype and high total UMSARS scores were associated with constipation in MSA. Similarly, the high total UMSARS scores were associated with constipation in MSA-P and MSA-C patients. Among the 107 patients with constipation, 59.8% began experiencing it before the onset of motor symptoms, and the interval between constipation and occurrence of motor symptoms was significantly longer in these patients than in those who experienced constipation after onset of motor symptoms.ConclusionConstipation is a highly prevalent non-motor symptom in MSA and more often occurs before the onset of motor symptoms. The results of this study may help guide future research into MSA pathogenesis in its earliest stages.
Reduction of the vertical vestibular-ocular reflex in military aircraft pilots exposed to tactical, high-performance flight
Authors: Bertolini Giovanni , Pagnamenta Alberto , Kunz Andres , Del Torso Aleardo , Bron Denis 
Published: June 2023

BackgroundExposure to high-performance flight stresses the vestibular system and may lead to adaptive changes in the vestibular responses of pilots. We investigated the vestibular-ocular reflex of pilots with different histories of flight exposure both with respect to hours of flight and flight conditions (tactical, high-performance vs. non-high-performance) to evaluate if and how adaptative changes are observable.MethodsWe evaluated the vestibular-ocular reflex of aircraft pilots using the video Head Impulse Test. In study 1, we assessed three groups of military pilots: Group 1 had 68 pilots with few hours of flight experience (&lt;300 h) in non-high-performance flight conditions; Group 2 had 15 pilots with many hours of flight (&gt;3,000 h) and regularly flying tactical, high-performance flight conditions; Group 3 had eight pilots with many hours of flight (&gt;3,000 h) but not exposed to tactical, high-performance flight conditions. In study 2, four trainee pilots were followed up and tested three times over a 4-year period: (1) &lt;300 h of flight on civil aircraft; (2) shortly after exposure to aerobatic training and with &lt;2,000 h of overall flight; and (3) after training on tactical, high-performance aircraft (F/A 18) and for more than 2,000 h of flight.ResultsStudy 1: Pilots of tactical, high-performance aircrafts (Group 2) had significantly lower gain values (p &lt; 0.05) as compared to Groups 1 and 3, selectively for the vertical semicircular canals. They also had a statistically (p = 0.022) higher proportion (0.53) of pathological values in at least one vertical semicircular canal as compared to the other groups. Study 2: A statistically significant (p &lt; 0.05) decrease in the rVOR gains of all vertical semicircular canals, but not of the horizontal canals, was observed. Two pilots had a pathological value in at least one vertical semicircular canal in the third test.DiscussionThe results evidence a decrease in the gain of the vestibular-ocular reflex as measured with the video head impulse test for the vertical canals. This decrease appears to be associated with the exposure to tactical, high-performance flight rather than with the overall flight experience.
Characteristic analysis and identification of novel molecular biomarkers in elderly glioblastoma patients using the 2021 WHO Classification of Central Nervous System Tumors
Authors: Wang Yaning , Li Junlin , Cao Yaning , Chen Wenlin , Xing Hao , Guo Xiaopeng , Shi Yixin , Wang Yuekun , Liang Tingyu , Ye Liguo , Liu Delin , Yang Tianrui , Wang Yu , Ma Wenbin 
Published: June 2023

IntroductionElderly glioblastoma (GBM) patients is characterized by high incidence and poor prognosis. Currently, however, there is still a lack of adequate molecular characterization of elderly GBM patients. The fifth edition of the WHO Classification of Central Nervous System Tumors (WHO5) gives a new classification approach for GBM, and the molecular characteristics of elderly GBM patients need to be investigated under this new framework.MethodsThe clinical and radiological features of patients with different classifications and different ages were compared. Potential prognostic molecular markers in elderly GBM patients under the WHO5 classification were found using Univariate Cox regression and Kaplan–Meier survival analysis.ResultsA total of 226 patients were included in the study. The prognostic differences between younger and elderly GBM patients were more pronounced under the WHO5 classification. Neurological impairment was more common in elderly patients (p = 0.001), while intracranial hypertension (p = 0.034) and epilepsy (p = 0.038) were more common in younger patients. Elderly patients were more likely to have higher Ki-67(p = 0.013), and in elderly WHO5 GBM patients, KMT5B (p = 0.082), KRAS (p = 0.1) and PPM1D (p = 0.055) were each associated with overall survival (OS). Among them, KRAS and PPM1D were found to be prognostic features unique to WHO5 elderly GBM patients.ConclusionOur study demonstrates that WHO5 classification can better distinguish the prognosis of elderly and younger GBM. Furthermore, KRAS and PPM1D may be potential prognostic predictors in WHO5 elderly GBM patients. The specific mechanism of these two genes in elderly GBM remains to be further studied.
Association of leisure sedentary behavior and physical activity with the risk of nonalcoholic fatty liver disease: a two-sample Mendelian randomization study
Authors: Zhang Xicheng , Chen Keke , Yin Shangyu , Qian Mengao , Liu Changbao 
Published: June 2023

IntroductionPrevious observational studies have demonstrated the relationship between leisure sedentary behavior, physical activity, and nonalcoholic liver disease (NAFLD). However, whether these associations are causal or confounding factors remains unclear.MethodsPooled genetic data from the UK Biobank and other large genome-wide association studies (GWAS) were used to extract instrumental variables representing sedentary television watching, computer use, driving, vigorous physical activity (VPA), and moderate-to-vigorous physical activity (MVPA). The two-sample Mendelian randomization (MR) method was used to explain the causal relationship between them and NAFLD. The inverse variance of the weighted method was used as the main analysis method, and MR-Egger, weighted median, MR-PRESSO, and other supplementary methods were also used. A sensitivity analysis was also performed. Simultaneously, the common risk factors for NAFLD were further analyzed for potential mediating associations.ResultsWe observed that sedentary television viewing (odds ratio (OR): 1.84; 95% confidence interval (CI): 1.09–3.10; p = 0.021) and genetically predicted VPA duration (OR: 0.0033; 95% CI: 0.000015–0.70; p = 0.036) were suggestively associated with the risk of NAFLD. Using a computer (OR: 1.51; 95% CI: 0.47–4.81; p = 0.484), driving (OR: 0.78; 95% CI: 0.05–11.94; p = 0.858), and MVPA time (OR: 0.168; 95% CI: 0.01–2.81; p = 0.214) were not significantly associated with NAFLD. The role of heterogeneity versus pleiotropy was limited in all the analyses.DiscussionThis study supports the association between sedentary television watching and an increased risk of NAFLD, along with vigorous physical activity as a possible protective factor for NAFLD.
Bioinformatics and pathway enrichment analysis identified hub genes and potential biomarker for gastric cancer prognosis
Authors: Darang Elham , Pezeshkian Zahra , Mirhoseini Seyed Ziaeddin , Ghovvati Shahrokh 
Published: June 2023

IntroductionGastric cancer is one of the most common cancers in the world. This study aimed to identify genes, biomarkers, and metabolic pathways affecting gastric cancer using bioinformatic analysis and meta-analysis. MethodsDatasets containing gene expression profiles of tumor lesions and adjacent non-tumor mucosa samples were downloaded. Common differentially expressed genes between data sets were selected to identify hub genes and further analysis. Gene Expression Profiling and Interactive Analyses (GEPIA) and the Kaplan-Meier method were used to further validate the expression level of genes and plot the overall survivalcurve, respectively.Results and disscussionKEGG pathway analysis showed that the most important pathway was enriched in ECM-receptor interaction. Hub genes includingCOL1A2, FN1, BGN, THBS2, COL5A2, COL6A3, SPARC and COL12A1 wereidentified. The top interactive miRNAs including miR-29a-3p, miR-101-3p,miR-183-5p, and miR-15a-5p targeted the most hub genes. The survival chart showed an increase in mortality in patients with gastric cancer, which shows the importance of the role of these genes in the development of the disease and can be considered candidate genes in the prevention and early diagnosis of gastric cancer.
Effect of neonatal breast crawl on breastfeeding: a prospective cohort study
Authors: Pang Yan , Wang Xin , Li Huimin , Tu Suhua 
Published: June 2023

AimTo analyse the effect of breast crawl on neonatal breastfeeding within 5 months of delivery.DesignProspective Cohort Study.MethodsNeonates were divided into successful and failed groups, according to whether the newborn crawled to the breast and began sucking for the first time within 1 h after delivery. The initiation of lactation and breastfeeding duration of the two groups were analysed at 24 h, 48 h, 72 h, the feeding practices were followed-up on the 7th day, 42nd day, and 5th month in order to explore the long-term benefits of breast crawl on breastfeeding.ResultsA total of 163 neonates were included. The initiation time and the duration of first feeding, the lactation initiation in the successful group was earlier, the scores of first and in-hospital breastfeeding scales were higher.Public ContributionBreast crawl is the preferred method for mothers to begin breastfeeding. The delivery room is the place where the first breast crawl occurs immediately after delivery. The midwife is the key person to protect this valuable behavior. Therefore, the midwife needs provide valuable opportunities for the breast crawl of the newborn and promote this behavior.
Short-term anti-remodeling effects of gliflozins in diabetic patients with heart failure and reduced ejection fraction: an explainable artificial intelligence approach
Authors: Mele Marco , Imbrici Paola , Mele Antonietta , Togo Maria Vittoria , Dinoi Giorgia , Correale Michele , Brunetti Natale Daniele , Nicolotti Orazio , De Luca Annamaria , Altomare Cosimo Damiano , Liantonio Antonella , Amoroso Nicola 
Published: June 2023

Introduction: Sodium-glucose cotransporter type 2 inhibitors (SGLT2i), gliflozins, play an emerging role for the treatment of heart failure with reduced left ventricular ejection fraction (HFrEF). Nevertheless, the effects of SGLT2i on ventricular remodeling and function have not been completely understood yet. Explainable artificial intelligence represents an unprecedented explorative option to clinical research in this field. Based on echocardiographic evaluations, we identified some key clinical responses to gliflozins by employing a machine learning approach.Methods: Seventy-eight consecutive diabetic outpatients followed for HFrEF were enrolled in the study. Using a random forests classification, a single subject analysis was performed to define the profile of patients treated with gliflozins. An explainability analysis using Shapley values was used to outline clinical parameters that mostly improved after gliflozin therapy and machine learning runs highlighted specific variables predictive of gliflozin response.Results: The five-fold cross-validation analyses showed that gliflozins patients can be identified with a 0.70 ± 0.03% accuracy. The most relevant parameters distinguishing gliflozins patients were Right Ventricular S'-Velocity, Left Ventricular End Systolic Diameter and E/e' ratio. In addition, low Tricuspid Annular Plane Systolic Excursion values along with high Left Ventricular End Systolic Diameter and End Diastolic Volume values were associated to lower gliflozin efficacy in terms of anti-remodeling effects.Discussion: In conclusion, a machine learning analysis on a population of diabetic patients with HFrEF showed that SGLT2i treatment improved left ventricular remodeling, left ventricular diastolic and biventricular systolic function. This cardiovascular response may be predicted by routine echocardiographic parameters, with an explainable artificial intelligence approach, suggesting a lower efficacy in case of advanced stages of cardiac remodeling.
A low-calorie diet raises β-aminoisobutyric acid in relation to glucose regulation and leptin independent of exercise in women with obesity
Authors: Faiz Habiba , Malin Steven K. 
Published: June 2023

Introduction: β-aminoisobutyric acid (BAIBA) is a suggested cytokine secreted from skeletal muscles that regulates insulin sensitivity, pancreatic function, and fat oxidation. However, no studies to date have examined if a low-calorie diet (LCD) or LCD + with interval exercise (LCD + INT) differentially raises BAIBA. The purpose was to examine if LCD or LCD + INT raises circulating BAIBA in relation to cardiometabolic health.Methods: For this, twenty-three women with obesity were randomized to either 2-weeks of LCD (n = 12, 48.4 ± 2.5 y, 37.84 ± 1.5 kg/m2; ∼1200 kcal/day) or LCD + INT (n = 11, 47.6 ± 4.3 y, 37.9 ± 2.3 kg/m2; ∼60 min/d of INT alternating 3 min of 90% and 50% HRpeak), with matched energy availability. Fasting BAIBA and adipokines along with glucose, insulin, C-peptide, and FFA after every 30 min up to 120 min were obtained during a 75 g OGTT to estimate total area under the curve (tAUC), insulin sensitivity (SIIS), pancreatic function [disposition index (DI)], and hepatic insulin clearance (HIC). Fuel use (indirect calorimetry) was tested at 0, 60, and 120 min of the OGTT along with fitness (VO2peak) and body composition (BodPod).Results: Both treatments lowered body weight (p &lt; 0.001) and leptin (p &lt; 0.001) but raised BAIBA (p = 0.007) and insulin sensitivity (p = 0.02). LCD + INT increased VO2peak (p = 0.02) and REE tAUC120min (p = 0.02) while LCD and LCD + INT decreased carbohydrate oxidation (CHOox) tAUC120min (p &lt; 0.001). Increased BAIBA associated with reduced weight (r = −0.67, p &lt; 0.001), leptin (r = −0.66, p = 0.001), CHOox tAUC120min (r = −0.44, p = 0.03) and DImuscle120min (r = −0.45, p = 0.03), but elevated HIC120min (r = 0.47, p = 0.02).Discussion: Concluding, LCD and LCD + INT increased BAIBA in relation to reduced body weight and pancreatic function in women with obesity. This suggests energy deficit is a key factor regulating circulating BAIBA.
Exploring public attention and sentiment toward carbon neutrality: evidence from Chinese social media Sina Weibo
Authors: Wang Bo , Jiang Zixiao , Cheng Dawei , Wang Ziao 
Published: June 2023

IntroductionExploring the public’s cognition toward carbon neutrality is conducive to improving the quality and effectiveness of policymaking, and promoting the realization of carbon neutrality goals. This study aims to explore the public’s attention and sentiment toward carbon neutrality from the perspective of social psychology.MethodsUsing posts on carbon neutrality from the Chinese social media platform Sina Weibo as the data source, this study uses statistical analysis, the Mann-Kendall method, keyword analysis, the BERT model, and the LDA model to explore public attention and sentiment.ResultsThe results show that: (1) men, people living east of the Hu line (economically developed regions), and the public in the energy finance market are more concerned about carbon neutrality; (2) high public attention and great dynamic changes in public attention toward carbon neutrality could be trigged by highly credible government or international governmental organizations’ information; (3) public sentiment toward carbon neutrality is mostly positive; however, specific topics affect public sentiment differently.DiscussionThe research results contribute to policymakers’ better understanding of the trend of public attention and sentiment toward carbon neutrality, and support improvements in the quality and impact of policymaking.
The effective on intradermal acupuncture based on changes in biological specificity of acupoints for major depressive disorder: study protocol of a prospective, multicenter, randomized, controlled trial
Authors: Tu Mingqi , Wu Xiaoting , Qu Siying , Jin Junyan , Chen Nisang , Xiong Sangsang , Pei Shuangyi , Li Xinwei , Shi Yan , Hu Hantong , Li Xiaoyu , Fang Jianqiao , Shao Xiaomei 
Published: June 2023

BackgroundAntidepressants still have some side effects in treating major depressive disorder (MDD), and acupuncture therapy is a complementary therapy of research interest for MDD. Acupoints are sensitive sites for disease response and stimulation points for acupuncture treatment. Prior studies suggest that the biological specificity of acupoints is altered in physiological and pathological situations. Therefore, we hypothesize that the biological specificity of acupoints is associated with the diagnosis of MDD and that stimulating acupoints with significant biological specificity can achieve a better therapeutic effect than clinical common acupoints. This study aims to investigate the efficacy and safety of intradermal acupuncture (IA) treatment for MDD based on changes in the biological specificity of acupoints.MethodsThe first part of the study will enroll 30 MDD patients and 30 healthy control (HC) participants to assess pain sensitivity and thermal specificity of MDD-related acupoints using a pressure pain threshold gauge (PTG) and infrared thermography (IRT). The potentially superior acupoints for treating MDD will be selected based on the results of PTG and IRT tests and referred to as pressure pain threshold strong response acupoints (PSA) and temperature strong response acupoints (TSA).The second part of the study will enroll 120 eligible MDD patients randomly assigned to waiting list (WL) group, clinical common acupoint (CCA) group, TSA group, and PSA group in a 1:1:1:1 ratio. The change in the Patient Health Questionnaire-9 Items (PHQ-9), the MOS item short-form health survey (SF-36), pressure pain threshold, temperature of acupoints, and adverse effects will be observed. The outcomes of PHQ-9 and SF-36 measures will be assessed before intervention, at 3 and 6 weeks after intervention, and at a 4-week follow-up. The biological specificity of acupoint measures will be assessed before intervention and at 6 weeks after intervention. All adverse effects will be assessed.DiscussionThis study will evaluate the therapeutic effect and safety of IA for MDD based on changes in the biological specificity of acupoints. It will investigate whether there is a correlation between the biological specificity of MDD-related acupoints and the diagnosis of MDD and whether stimulating strong response acupoints is superior to clinical common acupoints in the treatment of MDD. The study’s results may provide insights into the biological mechanisms of acupuncture and its potential as a complementary therapy for MDD.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT05524519.
Adverse short-term effects of ozone on cardiovascular mortalities modified by season and temperature: a time-series study
Authors: Gao Panjun , Wu Yongsheng , He Lihuan , Wang Li , Fu Yingbin , Chen Jinrong , Zhang Fengying , Krafft Thomas , Martens Pim 
Published: June 2023

IntroductionAmbient ozone pollution becomes critical in China. Conclusions on the short-term effects of ozone on cardiovascular mortality have been controversial and limited on cause-specific cardiovascular mortalities and their interactions with season and temperature. This research aimed to investigate the short-term effects of ozone and the modifications of season and temperature on cardiovascular mortality.MethodsCardiovascular death records, air pollutants, and meteorological factors in Shenzhen from 2013 to 2019 were analyzed. Daily 1-h maximum of ozone and daily maximum 8-h moving average of ozone were studied. Generalized additive models (GAMs) were applied to evaluate their associations with cardiovascular mortalities in sex and age groups. Effect modifications were assessed by stratifying season and temperature.ResultsDistributed lag impacts of ozone on total cardiovascular deaths and cumulative effects on mortality due to ischemic heart disease (IHD) were most significant. Population under 65 years old was most susceptible. Majority of significant effects were found in warm season, at high temperature, and at extreme heat. Ozone-associated risks in total deaths caused by hypertensive diseases reduced in warm season, while risks in IHD in males increased at high temperature. Extreme heat enhanced ozone effects on deaths caused by CVDs and IHD in the population under 65 years old.DiscussionThe revealed cardiovascular impacts of ozone below current national standard of air quality suggested improved standards and interventions in China. Higher temperature, particularly extreme heat, rather than warm season, could significantly enhance the adverse effects of ozone on cardiovascular mortality in population under 65 years old.