bluuebunny/crossref_metadata_2025_split huggingface dataset:
The causal relationship between sleep and risk of psychiatric disorders: A two-sample mendelian randomization study
Authors: Chen Pei , Qin Jiuhang , Wang Yueying , Yuan Jinjin , Pan Yang , Zhu Bingqian 
Published: June 2024

IntroductionSleep is associated with psychiatric disorders. However, their causality remains unknown.MethodsThe study explored the causal relationship between seven sleep parameters (sleep duration, insomnia, sleep apnea, chronotype, daytime dozing, napping during the day, and snoring) and three psychiatric disorders including major depressive disorder (MDD), schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for sleep parameters were obtained from the United Kingdom biobank, FinnGen biobank, and EBI databases. MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW(fixed effects) were used to perform the MR analysis. The heterogeneity was detected by Cochran’s Q statistic. The horizontal pleiotropy was detected by MR Egger. The sensitivity was investigated by the leave-one-out analysis.ResultsInsomnia (OR = 2.02, 95%CI = 1.34–3.03, p = 0.001, False-discovery rate (FDR) corrected p-value = 0.011) and napping during the day (OR = 1.81, 95%CI = 1.34–2.44, FDR corrected p-value&lt;0.001) were associated with an increased risk of MDD. Longer sleep duration (OR = 2.20, 95%CI = 1.24–3.90, FDR corrected p-value = 0.049) had an association with the increased risk of schizophrenia, while daytime dozing (OR = 4.44, 95%CI = 1.20–16.41, corrected p-value = 0.088)and napping during the day (OR = 2.11, 95%CI = 1.11–4.02, FDR corrected p-value = 0.088) had a suggestive association with an increased risk of schizophrenia. Longer sleep duration had a suggestive association with a decreased risk of ADHD (OR = 0.66, 95%CI = 0.42–0.93, FDR corrected p-value = 0.088).ConclusionThis study provides further evidence for a complex relationship between sleep and psychiatric disorders. Our findings highlight the potential benefits of addressing sleep problems in the prevention of psychiatric disorders.
Sulfur dioxide inhibits mast cell degranulation by sulphenylation of galectin-9 at cysteine 74
Authors: Song Jiaru , Zheng Jie , Li Zongmin , Fu Ling , Yang Jing , Li Kun , Yu Xiaoqi , Lv Boyang , Du Junbao , Huang Yaqian , Jin Hongfang 
Published: June 2024

ObjectivesMast cell (MC) degranulation is a key process in allergic reactions and inflammatory responses. Aspartate aminotransferase 1 (AAT1)-derived endogenous sulfur dioxide (SO2) is an important regulator of MC function. However, the mechanism underlying its role in MC degranulation remains unclear. This study aimed to investigate the mechanism by which endogenous SO2 controlled MC degranulation.MethodsHMC-1 and Rat basophilic leukemia cell MC line (RBL-2H3) were used in the cell experiments. SO2 content was detected by in situ fluorescent probe. MC degranulation represented by the release rate of MC β-hexosaminidase was determined using a colorimetric assay. Sulfenylation of galectin-9 (Gal-9) in MCs and purified protein was detected using a biotin switch assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the exact sulfenylation sites of Gal-9 by SO2. Animal models of passive cutaneous anaphylaxis (PCA) and hypoxia-driven pulmonary vascular remodeling were used to investigate the effect of SO2 on mast cell activation in vivo. Site-directed mutation of Gal-9 was conducted to confirm the exact site of SO2 and support the significance of SO2/Gal-9 signal axis in the regulation of MC degranulation.ResultsDegranulation was increased in AAT1-knockdowned MCs, and SO2 supplementation reversed the increase in MC degranulation. Furthermore, deficiency of endogenous SO2 contributed to IgE-mediated degranulation in vitro. Besides, SO2 inhibited IgE-mediated and hypoxia-driven MC degranulation in vivo. Mechanistically, LC-MS/MS analysis and site-directed mutation results showed that SO2 sulfenylated Gal-9 at cysteine 74. Sulfenylation of the 74th cysteine of Gal-9 protein was required in the SO2-inhibited MC degranulation under both physiological and pathophysiological conditions.ConclusionThese findings elucidated that SO2 inhibited MC degranulation via sulfenylating Gal-9 under both physiological and pathophysiological conditions, which might provide a novel treatment approach for MC activation-related diseases.
Peripheral PD-1+NK cells could predict the 28-day mortality in sepsis patients
Authors: Tang Jia , Shang Chenming , Chang Yue , Jiang Wei , Xu Jun , Zhang Leidan , Lu Lianfeng , Chen Ling , Liu Xiaosheng , Zeng Qingjia , Cao Wei , Li Taisheng 
Published: June 2024

BackgroundUnbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model.MethodsPatients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis.ResultsThe study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38+CD8+T cells, PD-1+NK cells, HLA-DR+CD8+T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1+ NK cells, while cluster 2 featured higher proportions of naïve CD4+T cells. Furthermore, the level of PD-1+NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, P&lt;0.01). Moreover, the levels of PD1+ NK cells combined with SOFA score showed good performance in predicting the 28-day mortality in sepsis (AUC=0.91,95%CI 0.82–0.99), which is superior to PD1+ NK cells only(AUC=0.69, sensitivity 0.74, specificity 0.64, cut-off value of 11.25%). In the multivariate Cox regression, high expression of PD1+ NK cells proportion was related to 28-day mortality (aHR=1.34, 95%CI 1.19 to 1.50; P&lt;0.001).ConclusionThe study provides novel insights into the association between PD1+NK cell profiles and prognosis of sepsis. Peripheral immunophenotyping could potentially stratify the septic patients and identify those with a high risk of 28-day mortality.
Changes in primary care visits for respiratory illness during the COVID-19 pandemic: a multinational study by the International Consortium of Primary Care Big Data Researchers (INTRePID)
Authors: Westfall John M. , Bonilla Angela Ortigoza , Lapadula María C. , Zingoni Paula L. , Wong William C. W. , Wensaas Knut A. , Pace Wilson D. , Silva-Valencia Javier , Scattini Luciano F. , Ng Amy P. P. , Manski-Nankervis Jo-Anne , Ling Zheng J. , Li Zhuo , Heald Adrian H. , Laughlin Adrian , Kristiansson Robert S. , Hallinan Christine M. , Goh Lay H. , Gaona Gabriela , Flottorp Signe , de Lusignan Simon , Cuba-Fuentes María S. , Baste Valborg , Tu Karen ,   on behalf of INTRePID
Published: June 2024

ObjectivesThe majority of patients with respiratory illness are seen in primary care settings. Given COVID-19 is predominantly a respiratory illness, the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID), assessed the pandemic impact on primary care visits for respiratory illnesses.DesignDefinitions for respiratory illness types were agreed on collectively. Monthly visit counts with diagnosis were shared centrally for analysis.SettingPrimary care settings in Argentina, Australia, Canada, China, Norway, Peru, Singapore, Sweden and the United States.ParticipantsOver 38 million patients seen in primary care settings in INTRePID countries before and during the pandemic, from January 1st, 2018, to December 31st, 2021.Main outcome measuresRelative change in the monthly mean number of visits before and after the onset of the pandemic for acute infectious respiratory disease visits including influenza, upper and lower respiratory tract infections and chronic respiratory disease visits including asthma, chronic obstructive pulmonary disease, respiratory allergies, and other respiratory diseases.ResultsINTRePID countries reported a marked decrease in the average monthly visits for respiratory illness. Changes in visits varied from −10.9% [95% confidence interval (CI): −33.1 to +11.3%] in Norway to −79.9% (95% CI: −86.4% to −73.4%) in China for acute infectious respiratory disease visits and − 2.1% (95% CI: −12.1 to +7.8%) in Peru to −59.9% (95% CI: −68.6% to −51.3%) in China for chronic respiratory illness visits. While seasonal variation in allergic respiratory illness continued during the pandemic, there was essentially no spike in influenza illness during the first 2 years of the pandemic.ConclusionThe COVID-19 pandemic had a major impact on primary care visits for respiratory presentations. Primary care continued to provide services for respiratory illness, although there was a decrease in infectious illness during the COVID pandemic. Understanding the role of primary care may provide valuable information for COVID-19 recovery efforts and planning for future global emergencies.
Different effects of acute and chronic oxidative stress on the intestinal flora and gut-liver axis in weaned piglets
Authors: Zhang Hongyu , Xiang Xuan , Wang Chenyu , Li Tiejun , Xiao Xuping , He Liuqin 
Published: June 2024

IntroductionOxidative stress plays a pivotal role in modulating the balance of intestinal flora and the gut-liver axis, while also serving as a key determinant of the growth potential of weaned piglets. However, few studies have subdivided and compared acute and chronic oxidative stress.MethodsIn this study, an intestinal model of acute oxidative stress in weaned piglets using paraquat (PQ) and a chronic oxidative stress model using D-galactosa in weaned piglets were conducted. And we further systematically compare their effects.ResultsBoth acute and chronic oxidative stress models impaired intestinal barrier function and liver function. Chronic stress caused by D-galactose can result in severe redox dysregulation, while acute stress caused by paraquat can lead to inflammation and liver damage. Additionally, the components involved in the CAR pathway were expressed differently. Chronic or acute oxidative stress can reduce the diversity and composition of intestinal flora. In the PQ group, the richness of Mogibacterium and Denitratisoma improved, but in the D-gal group, the richness of Catenisphaera and Syntrophococcus increased.DiscussionNot only does this research deepen our understanding of the effects of acute and chronic oxidative stress on intestinal functions, but it also characterizes characteristic changes in the gut flora, potentially identifying novel therapeutic targets and opening new avenues for future research.
Dietary supplementation with Lactium and L-theanine alleviates sleep disturbance in adults: a double-blind, randomized, placebo-controlled clinical study
Authors: Lim Su Eun , Kim Ho Seok , Lee Siwoo , Kang Eun Young , Lim Jong-Hyun , Kim Byung-Yong , Shin Seon-Mi , Baek Younghwa 
Published: June 2024

IntroductionThe use of natural products for the treatment of sleep disturbances is increasing owing to the side effects and limitations of traditional sleep therapy. Moreover, recent studies have shown a significant correlation between sleep quality and gut microbiota composition. This study aimed to assess the impact of LTC-022, a commercially available dietary supplement containing Lactium and L-theanine, on enhancing sleep quality.MethodsForty participants experiencing sleep discomfort were enrolled in a double-blind randomized controlled trial, wherein they received LTC-022 or a placebo orally for 8 weeks. The effects of treatment on sleep quality were assessed using the Pittsburgh Sleep Quality Index and Insomnia Severity Index. To comprehensively evaluate changes in sleep patterns, various parameters were evaluated, including the time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), wake after sleep onset (WASO) counts, and bedtime. These parameters were derived from daily sleep logs recorded over the 8-week study period, categorized into weekdays and weekends. Stool samples were analyzed for microbiome composition. The V4 region of bacterial 16S rRNA genes was amplified using specific primers (515F and 806R) and targeted for analysis. Microbial diversity, including operational taxonomic units, the Shannon and Chao indices, the Firmicutes/Bacteroidetes (F/B) ratio, and the variety of bacterial taxa, was assessed.ResultsNo significant differences were observed in sleep quality and insomnia scale characteristics between the two groups. In-depth analysis using sleep diaries showed that WASO counts after 8 weeks and bedtime after 4 weeks showed significant differences between the LTC-022 and control groups. In the LTC-022 group, significant differences were observed in the increase in TST, decrease in SOL, increase in SE, decrease in WASO counts, and earlier bedtime. Microbiome analysis revealed that the abundance of the genera Blautia and Ruminococcus increased in fecal samples from the LTC-022 group.ConclusionThese results suggest that continuous LTC-022 intake has a beneficial effect on maintaining sleep duration and an appropriate bedtime. Additionally, changes in the gut microbiota may be linked to changes in sleep patterns resulting from the consumption of Lactium and L-theanine.Clinical trial registrationhttps://cris.nih.go.kr/cris/search/detailSearch.do/22841, KCT0007750.
The role of a radiopaque peri-rectal hydrogel spacer in aiding accurate daily image-guidance for prostate stereotactic radiotherapy
Authors: Icht Oded , Schlosser Shir , Weinstock-Sabbah Miriam , Rephael Mor , Bragilovski Dimitri , Moore Assaf , Shochat Tzippora , Limon Dror , Fredman Elisha 
Published: June 2024

IntroductionPrecise patient positioning with image guidance (IGRT) is essential for safe prostate radiotherapy. We present the first report of utilizing a CT-visible hydrogel spacer, used to decrease rectal radiation dose, as a surrogate fiducial marker to aid in daily IGRT with cone-beam CT (CBCT) in stereotactic radiotherapy (SABR) for prostate cancer.Materials and methodsPrior to CT simulation, patients underwent placement of three intraprostatic gold fiducial markers and radiopaque hydrogel spacer per standard practice. At treatment, after initial setup, a CBCT was acquired and fused to the planning CT based on 3-dimensional matching of the spacer. A second alignment was then performed based on the fiducial markers. The six directional shifts (three linear and three rotational) were recorded, and the differences compared.Results140 individual fractions across 41 consecutive patients were evaluated. Mean/median differences between hydrogel spacer-based and fiducial-based alignment in linear (vertical, longitudinal, lateral) and rotational (rotation, pitch, roll) shifts were 0.9/0.6mm, 0.8/0.5mm, and 0.6/0.4mm, and 0.38/0, 0.62/0, and 0.35/0 degrees, respectively. No difference was observed in 9.9%, 22.9%, and 22.14% of linear shifts, and 65.7%, 65%, and 66.4% rotational shifts, respectively. Significantly smaller differences were observed in the latter 70 fractions vs. the former, and results were consistent across evaluators.ConclusionsFor precise daily IGRT with CBCT for prostate SABR, alignment using a radiopaque hydrogel spacer was highly comparable to intraprostatic fiducial markers. This represents the first report supporting an additional indication of IGRT for a CT-visible hydrogel spacer, to further enhance treatment accuracy and potentially obviate the need for the additional fiducial marker procedure.
Machine learning for screening and predicting the availability of medications for children: a cross-sectional survey study
Authors: Guo Jing-yan 
Published: June 2024

ObjectiveThe aim of the study was to explore the factors influencing the availability of medications for children, and establish a machine learning model to provide an empirical basis for the subsequent formulation and improvement of relevant policies.MethodsDesign: Cross-sectional survey. Setting: 12 provinces, China. Medical doctors from 25 public hospitals were enrolled. All data were randomly divided into a training set and a validation set at a ratio of 7:3. Three prediction models, namely random forest (RF), logistic regression (LR), and extreme gradient boosting (XGBoost), were developed and compared. The receiver operating characteristic curve (ROC) and the associated area under the curve (AUC) were used to evaluate the three models. A nomogram and clinical impact curve (CIC) for availability of medication were developed.ResultsFifteen of 29 factors in the database that were most likely to be selected were considered to establish the prediction model. The XGBoost model (AUC = 0.915) demonstrated better performance than the RF model (AUC = 0.902) and the LR model (AUC = 0.890). According to the Shapley additive explanation values, the five factors that most significantly affected the availability of medications for children in the XGboost model were as follows: the relatively small number of specialized dosage forms for children; unaffordable medications for children; public education on the accessibility and safety of medication for children; uneven distribution of medical resources, leading to insufficient access to medication for children; and years of service as a doctor. The CIC was used to assess the practical applicability of the factor prediction nomogram.ConclusionsThe XGBoost model can be used to establish a prediction model to screen the factors associated with the availability of medications for children. The most important contributing factors to the models were the following: the relatively small number of specialized dosage forms for children; unaffordable medications for children; public education on the accessibility and safety of medication for children; uneven distribution of medical resources, leading to insufficient access to medication for children; and years of service as a doctor.
Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies
Authors: Sun Aru , Yang Haoyu , Li Tao , Luo Jinli , Zhou Ling , Chen Rui , Han Lin , Lin Yiqun 
Published: June 2024

Background: Metabolic imbalance is the common basis of many diseases. As natural isoquinoline alkaloid, berberine (BBR) has shown great promise in regulating glucose and lipids metabolism and treating metabolic disorders. However, the related mechanism still lacks systematic research.Aim: To discuss the role of BBR in the whole body’s systemic metabolic regulation and further explore its therapeutic potential and targets.Method: Based on animal and cell experiments, the mechanism of BBR regulating systemic metabolic processes is reviewed. Potential metabolism-related targets were summarized using Therapeutic Target Database (TTD), DrugBank, GeneCards, and cutting-edge literature. Molecular modeling was applied to explore BBR binding to the potential targets.Results: BBR regulates the whole-body metabolic response including digestive, circulatory, immune, endocrine, and motor systems through adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), sirtuin (SIRT)1/forkhead box O (FOXO)1/sterol regulatory element-binding protein (SREBP)2, nuclear factor erythroid 2-related factor (Nrf) 2/heme oxygenase (HO)-1, and other signaling pathways. Through these reactions, BBR exerts hypoglycemic, lipid-regulating, anti-inflammatory, anti-oxidation, and immune regulation. Molecular docking results showed that BBR could regulate metabolism targeting FOXO3, Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (Gpx) 4 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Evaluating the target clinical effects, we found that BBR has the therapeutic potential of anti-aging, anti-cancer, relieving kidney disease, regulating the nervous system, and alleviating other chronic diseases.Conclusion: This review elucidates the interaction between potential targets and small molecular metabolites by exploring the mechanism of BBR regulating metabolism. That will help pharmacologists to identify new promising metabolites interacting with these targets.
Development and validation of a drug clinical trial participation feelings questionnaire for cancer patients
Authors: Guo Chaowei , Xing Shujun , Zhao Guo , Wu Dawei , Li Ning , Wang Shuhang , Yu Ling 
Published: June 2024

ObjectiveThe study was designed to develop and validate a new drug clinical trial participation feelings questionnaire (DCTPFQ) for cancer patients.MethodsData collection and analysis involved a combination of qualitative and quantitative methods. There were two phases to this study. Phase Ⅰ involved developing a questionnaire to establish a list of items to be included in the pool: A theoretical framework was constructed based on the transitions theory and the Roper–Logan–Tierney theory. After incorporating a theoretical framework, interviewing participants, and reviewing the literature, 44 items were generated. After a Delphi consultation and a pilot test, 36 items proceeded to item analysis and exploratory factor analysis (EFA), and a four-factor structure with 21 items was formed. Confirmatory factor analysis (CFA), test–retest reliability, criteria-related validity, and internal consistency tests were conducted in phase II to examine the psychometric properties.ResultsThere were 21 items on the DCTPFQ, ranging from 1 (fully disagree) through 5 (fully agree). As a result of EFA and CFA, the four factors of DCTPFQ could be verified, including cognitive engagement, subjective experience, medical resources, and relatives and friends’ support. Test–retest reliability of the DCTPFQ was 0.840, and Cronbach’s alpha was 0.934. DCTPFQ is significantly correlated with the Fear of Progression Questionnaire—short form (r = 0.731, p &lt; 0.05) and the Mishel’s Uncertainty in Illness Scale (r = 0.714, p &lt; 0.05).ConclusionThe DCTPFQ is a useful tool for measuring the drug clinical trial participation feelings among cancer patients.