bluuebunny/crossref_metadata_2025_split huggingface dataset:
The identification of new roles for nicotinamide mononucleotide after spinal cord injury in mice: an RNA-seq and global gene expression study
Authors: Zhang Chunjia , Li Yan , Bai Fan , Talifu Zuliyaer , Ke Han , Xu Xin , Li Zehui , Liu Wubo , Pan Yunzhu , Gao Feng , Yang Degang , Wang Xiaoxin , Du Huayong , Guo Shuang , Gong Han , Du Liangjie , Yu Yan , Li Jianjun 
Published: December 2023

BackgroundNicotinamide mononucleotide (NMN), an important transforming precursor of nicotinamide adenine dinucleotide (NAD+). Numerous studies have confirmed the neuroprotective effects of NMN in nervous system diseases. However, its role in spinal cord injury (SCI) and the molecular mechanisms involved have yet to be fully elucidated.MethodsWe established a moderate-to-severe model of SCI by contusion (70 kdyn) using a spinal cord impactor. The drug was administered immediately after surgery, and mice were intraperitoneally injected with either NMN (500 mg NMN/kg body weight per day) or an equivalent volume of saline for seven days. The central area of the spinal cord was harvested seven days after injury for the systematic analysis of global gene expression by RNA Sequencing (RNA-seq) and finally validated using qRT-PCR.ResultsNMN supplementation restored NAD+ levels after SCI, promoted motor function recovery, and alleviated pain. This could potentially be associated with alterations in NAD+ dependent enzyme levels. RNA sequencing (RNA-seq) revealed that NMN can inhibit inflammation and potentially regulate signaling pathways, including interleukin-17 (IL-17), tumor necrosis factor (TNF), toll-like receptor, nod-like receptor, and chemokine signaling pathways. In addition, the construction of a protein-protein interaction (PPI) network and the screening of core genes showed that interleukin 1β (IL-1β), interferon regulatory factor 7 (IRF 7), C-X-C motif chemokine ligand 10 (Cxcl10), and other inflammationrelated factors, changed significantly after NMN treatment. qRT-PCR confirmed the inhibitory effect of NMN on inflammatory factors (IL-1β, TNF-α, IL-17A, IRF7) and chemokines (chemokine ligand 3, Cxcl10) in mice following SCI.ConclusionThe reduction of NAD+ levels after SCI can be compensated by NMN supplementation, which can significantly restore motor function and relieve pain in a mouse model. RNA-seq and qRT-PCR systematically revealed that NMN affected inflammation-related signaling pathways, including the IL-17, TNF, Toll-like receptor, NOD-like receptor and chemokine signaling pathways, by down-regulating the expression of inflammatory factors and chemokines.
Causal relationship between levels of myeloperoxidase and obstructive sleep apnea: a bidirectional two-sample Mendelian randomization study
Authors: Tang Weihua , Li Fang , Huang Rui , Liu Peijun 
Published: December 2023

BackgroundSeveral observational studies have investigated the association between myeloperoxidase (MPO) and obstructive sleep apnea (OSA). However, the nature of this relationship remains uncertain due to potential selection and confounding biases. To resolve this, we conducted a bidirectional two-sample Mendelian randomization (MR) study to scrutinize the causal relationship between MPO and OSA.MethodsInstrumental variables (IVs) for OSA were sourced from the publicly available FinnGen dataset, encompassing 38,998 OSA cases and 336,659 controls. Data on MPO were sourced from a study of 21,758 individuals conducted by the European Bioinformatics Institute (EBI). The primary MR analysis utilized the inverse-variance weighted (IVW) method, with MR–Egger intercept and leave-one-out methods assessing pleiotropy and Cochran’s Q test determining heterogeneity.ResultsThe IVW analysis indicated a causal relationship between heightened MPO levels and an increased incidence of OSA. Individuals with elevated MPO levels manifested a higher propensity to develop OSA, exhibiting an odds ratio (OR) of 1.075 and a 95% confidence interval (CI) of 1.011–1.143 (p = 0.021). Conversely, the reciprocal analysis unveiled no significant association between OSA and heightened MPO levels (p = 0.643). No directional pleiotropy was identified through the MR–Egger intercept test (p &gt; 0.05).ConclusionOur study provides evidence of an association between elevated MPO levels and an increased incidence of OSA. However, OSA does not necessarily lead to elevated MPO levels. When patients present with high MPO levels, screening for OSA may be advisable, considering their clinical characteristics.
Relationship between immune nutrition index and all-cause and cause-specific mortality in U.S. adults with chronic kidney disease
Authors: Zhang Junlin , Xiao Xiang , Han Tianzhao , Liu Yuping , Shuai Ping 
Published: December 2023

ObjectiveThe available evidence regarding the association of immune nutrition status with chronic kidney disease (CKD) is limited. Thus, the present study examined whether immunonutrition indices were associated with renal function and mortality among CKD individuals.Research design and methodsThis study enrolled 6,099 U.S. adults with CKD from the NHANES 2005–2018 database. Participants were matched with National Death Index records until 31 December 2019 to determine mortality outcomes. The time-dependent receiver operating characteristic was utilized to identify the most effective index among the prognostic nutritional index (PNI), system inflammation score (SIS), Naples prognostic score (NPS), and controlling nutritional status (CONUT) for predicting mortality. Cox regression models were employed to evaluate the associations of immunonutrition indices with mortality in participants with CKD.ResultsThe PNI exhibited the strongest predictive power among the four indices evaluated and the restricted cubic spline analysis revealed a cutoff value of 51 for the PNI in predicting mortality. During a median follow-up of 72 months (39–115 months), a total of 1,762 (weighted 24.26%) CKD participants died from all causes. The Kaplan–Meier curve demonstrated a reduced risk of death for the subjects with a higher PNI compared to those in the lower group. Besides, after adjusting for multiple potential confounders, a higher PNI remained an independent predictor for lower risks of all-cause mortality (HR 0.80, 95%CI: 0.71–0.91, p &lt; 0.001) and cardiovascular disease (CVD) mortality (HR 0.69, 95%CI: 0.55–0.88, p = 0.002) in individuals with CKD.ConclusionIn CKD, a higher PNI level was significantly associated with lower mortality from all causes and CVD. Thus, the clinical utility of this immunonutrition indicator may facilitate risk stratification and prevent premature death among patients with CKD.
Ansofaxine hydrochloride inhibits tumor growth and enhances Anti-TNFR2 in murine colon cancer model
Authors: Jing Qianyu , Wan Quan , Nie Yujie , Luo Junqian , Zhang Xiangyan , Zhu Lan , Gui Huan , Li Linzhao , Wang Chenglv , Chen Shuanghui , Wang Mengjiao , Yuan Haohua , Lv Hang , Pan Runsang , Jing Qianjun , Nie Yingjie 
Published: December 2023

Introduction: As psychoneuroimmunology flourishes, there is compelling evidence that depression suppresses the anti-tumor immune response, promotes the progression of cancer, and inhibits the effectiveness of cancer immunotherapy. Recent studies have reported that antidepressants can not only alleviate the depressant condition of cancer patients, but also strengthen the anti-tumor immunity, thus suppressing tumors. Tumor necrosis factor receptor 2 (TNFR2) antagonistic antibodies (Anti-TNFR2) targeting tumor-infiltrating regulatory T cells (Tregs) has achieved great results in preclinical studies, and with a favorable toxicity profile than existing immunotherapies, and is expected to become a new generation of more effective treatment strategies. Understanding the effects of combination therapy with antidepressants and Anti-TNFR2 may help design new strategies for cancer immunotherapy.Methods: We treated CT26, HCT116, MCA38 and SW620 colon cancer cells with fluoxetine (0–50 µM), ansofaxine hydrochloride (0–50 µM) and amitifadine hydrochloride (0–150 µM) to examine their effects on cell proliferation and apoptosis. We explored the antitumor effects of ansofaxine hydrochloride in combination with or without Anti-TNFR in subcutaneously transplanted CT26 cells in tumor-bearing mouse model. Antitumor effects were evaluated by tumor volume. NK cell, M1 macrophage cell, CD4+ T cell, CD8+ T cell, exhausted CD8+ T and regulatory T cell (Tregs) subtypes were measured by flow cytometry. 5-hydroxytryptamine, dopamine and norepinephrine levels were measured by ELISA.Results: Oral antidepression, ansofaxine hydrochloride, enhanced peripheral dopamine levels, promoted CD8+T cell proliferation, promoted intratumoral infiltration of M1 and NK cells, decreased the proportion of tumor-infiltrating exhausted CD8+T cells, and strengthened anti-tumor immunity, thereby inhibiting colon cancer growth. In combination therapy, oral administration of ansofaxine hydrochloride enhanced the efficacy of Anti-TNFR2, and produced long-term tumor control in with syngeneic colorectal tumor-bearing mice, which was attributable to the reduction in tumor-infiltrating Treg quantity and the recovery of CD8+ T cells function.Discussion: In summary, our data reveal the role of ansofaxine hydrochloride in modulating the anti-tumor immunity. Our results support that exhausted CD8+T is an important potential mechanism by which ansofaxine hydrochloride activates anti-tumor immunity and enhances anti-tumor effects of anti-TNFR2.
The influence of herbal medicine on serum motilin and its effect on human and animal model: a systematic review
Authors: Cho Min-Seok , Park Jae-Woo , Kim Jinsung , Ko Seok-Jae 
Published: December 2023

Introduction: Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the migrating myoelectric complex component of GI motility. Changes in MLN availability are associated with GI diseases such as gastroesophageal reflux disease and functional dyspepsia. Furthermore, herbal medicines have been used for several years to treat various GI disorders. We systematically reviewed clinical and animal studies on how herbal medicine affects the modulation of MLN and subsequently brings the therapeutic effects mainly focused on GI function.Methods: We searched the PubMed, Embase, Cochrane, and Web of Science databases to collect all articles published until 30 July 2023, that reported the measurement of plasma MLN levels in human randomized controlled trials and in vivo herbal medicine studies. The collected characteristics of the articles included the name and ingredients of the herbal medicine, physiological and symptomatic changes after administering the herbal medicine, changes in plasma MLN levels, key findings, and mechanisms of action. The frequency patterns (FPs) of botanical drug use and their correlations were investigated using an FP growth algorithm.Results: Nine clinical studies with 1,308 participants and 20 animal studies were included in the final analyses. Herbal medicines in clinical studies have shown therapeutic effects in association with increased levels of MLN, including GI motility regulation and symptom improvement. Herbal medicines have also shown anti-stress, anti-tumor, and anti-inflammatory effects in vivo. Various biochemical markers may correlate with MLN levels. Markers may have a positive correlation with plasma MLN levels included ghrelin, acetylcholine, and secretin, whereas a negative correlation included triglycerides and prostaglandin E2. Markers, such as gastrin and somatostatin, did not show any correlation with plasma MLN levels. Based on the FP growth algorithm, Glycyrrhiza uralensis and Paeonia japonica were the most frequently used species.Conclusion: Herbal medicine may have therapeutic effects mainly on GI symptoms with involvement of MLN regulation and may be considered as an alternative option for the treatment of GI diseases. Further studies with more solid evidence are needed to confirm the efficacy and mechanisms of action of herbal medicines.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=443244, identifier CRD42023443244.
Forecasting infections with spatio-temporal graph neural networks: a case study of the Dutch SARS-CoV-2 spread
Authors: Croft V. Maxime , van Iersel Senna C. J. L. , Della Santina Cosimo 
Published: December 2023

The spread of an epidemic over a population is influenced by a multitude of factors having both spatial and temporal nature, which are hard to completely capture using first principle methods. This paper concerns regional forecasting of SARS-Cov-2 infections 1 week ahead using machine learning. We especially focus on the Dutch case study for which we develop a municipality-level COVID-19 dataset. We propose to use a novel spatiotemporal graph neural network architecture to perform the predictions. The developed model captures the spread of infectious diseases within municipalities over time using Gated Recurrent Units and the spatial interactions between municipalities using GATv2 layers. To the best of our knowledge, this model is the first to incorporate sewage data, the stringency index, and commuting information into GNN-based infection prediction. In experiments on the developed real-world dataset, we demonstrate that the model outperforms simple baselines and purely spatial or temporal models for the COVID-19 wild type, alpha, and delta variants. More specifically, we obtain an average R2 of 0.795 for forecasting infections and of 0.899 for predicting the associated trend of these variants.
Identification and analysis of BAHD superfamily related to malonyl ginsenoside biosynthesis in Panax ginseng
Authors: Wang Ping , Yan Yan , Yan Min , Piao Xiangmin , Wang Yingping , Lei Xiujuan , Yang He , Zhang Nanqi , Li Wanying , Di Peng , Yang Limin 
Published: December 2023

IntroductionThe BAHD (benzylalcohol O-acetyl transferase, anthocyanin O-hydroxycinnamoyl transferase, N-hydroxycinnamoyl anthranilate benzoyl transferase and deacetylvindoline 4-O-acetyltransferase), has various biological functions in plants, including catalyzing the biosynthesis of terpenes, phenolics and esters, participating in plant stress response, affecting cell stability, and regulating fruit quality. MethodsBioinformatics methods, real-time fluorescence quantitative PCR technology, and ultra-high-performance liquid chromatography combined with an Orbitrap mass spectrometer were used to explore the relationship between the BAHD gene family and malonyl ginsenosides in Panax ginseng. ResultsIn this study, 103 BAHD genes were identified in P. ginseng, mainly distributed in three major clades. Most PgBAHDs contain cis-acting elements associated with abiotic stress response and plant hormone response. Among the 103 genes, 68 PgBAHDs are WGD (whole-genome duplication) genes. The significance of malonylation in biosynthesis has garnered considerable attention in the study of malonyltransferases. The phylogenetic tree results showed 34 PgBAHDs were clustered with genes that have malonyl characterization. Among them, seven PgBAHDs (PgBAHD4, 45, 65, 74, 90, 97, and 99) showed correlations &gt; 0.9 with crucial enzyme genes involved in ginsenoside biosynthesis and &gt; 0.8 with malonyl ginsenosides. These seven genes were considered potential candidates involved in the biosynthesis of malonyl ginsenosides. DiscussionThese results help elucidate the structure, evolution, and functions of the P. ginseng BAHD gene family, and establish the foundation for further research on the mechanism of BAHD genes in ginsenoside biosynthesis.
Gender stereotypes and social perception of vocal confidence is mitigated by salience of socio-indexical cues to gender
Authors: Roche Jennifer M. , Asaro Katie , Morris Bradley J. , Morgan Shae D. 
Published: December 2023

IntroductionSocio-indexical cues to gender and vocal affect often interact and sometimes lead listeners to make differential judgements of affective intent based on the gender of the speaker. Previous research suggests that rising intonation is a common cue that both women and men produce to communicate lack of confidence, but listeners are more sensitive to this cue when it is produced by women. Some speech perception theories assume that listeners will track conditional statistics of speech and language cues (e.g., frequency of the socio-indexical cues to gender and affect) in their listening and communication environments during speech perception. It is currently less clear if these conditional statistics will impact listener ratings when context varies (e.g., number of talkers).MethodsTo test this, we presented listeners with vocal utterances from one female and one male-pitched voice (single talker condition) or many female/male-pitched voices (4 female voices; 4 female voices pitch-shifted to a male range) to examine how they impacted perceptions of talker confidence.ResultsResults indicated that when one voice was evaluated, listeners defaulted to the gender stereotype that the female voice using rising intonation (a cue to lack of confidence) was less confident than the male-pitched voice (using the same cue). However, in the multi-talker condition, this effect went away and listeners equally rated the confidence of the female and male-pitched voices.DiscussionFindings support dual process theories of information processing, such that listeners may rely on heuristics when speech perception is devoid of context, but when there are no differentiating qualities across talkers (regardless of gender), listeners may be ideal adapters who focus on only the relevant cues.
Buddhist culture as a safeguard for the subjective happiness of Chinese residents: mitigating anxiety regarding housing prices, unemployment, and inequality
Authors: Tan Shuying , Fang Peijie , Shi Wenxiang , Du Shukai 
Published: December 2023

IntroductionThis study examines whether Buddhist culture in China can safeguard the subjective happiness of residents by mitigating the detrimental impact of adversity. Considering Chinese traditional culture and referencing Baidu Search Index data, we focus on three sources of anxiety that are currently troubling Chinese residents: housing prices, unemployment, and inequality.MethodsWe conduct logit regressiontoinvestigate the mitigating impact of Buddhist culture on anxiety. The frequency of droughts and floods that occurred during the Ming and Qing dynasties are employed as instrumental variables for the local density of Buddhist culture to avoid endogeneity problems.ResultsEmpirical analysis based on microdata shows that Chinese Buddhist culture demonstrates the ability to alleviate the negative effects of housing price pressures, unemployment anxiety, and perceived inequality on subjective well-being. Mechanism analyses reveal that Chinese Buddhist culture plays a role in ameliorating the adverse impacts of housing and unemployment pressures on factors such as job satisfaction, physical health status, social trust, and expectations of future social standing. Moreover, it works to reduce inclinations toward social comparisons, thereby acting as a safeguard for happiness. Heterogeneity analysis shows that this insurance effect is more pronounced among vulnerable groups, including those in rural areas, middle-aged and elderly demographics, individuals with fewer social connections, lower social security coverage, and suboptimal health conditions.DiscussionThis study expands the landscape of happiness economics research and provides novel evidence about the correlation between religion and happiness. Psychotherapists may draw on certain aspects of religious philosophy in addressing mental disorders. From a governmental perspective, there is potential to effectively steer religious culture towards fostering social harmony and promoting economic development.
Community health workers’ quality of comprehensive care: a cross-sectional observational study across three districts in South Africa
Authors: Babalola Olukemi , Levin Jonathan , Goudge Jane , Griffiths Frances 
Published: December 2023

BackgroundCommunity healthcare worker (CHW) training programs are becoming increasingly comprehensive (an expanded range of diseases). However, the CHWs that the program relies on have limited training. Since CHWs’ activities occur largely during household visits, which often go unsupervised and unassessed, long-term, ongoing assessment is needed to identify gaps in CHW competency, and improve any such gaps. We observed CHWs during household visits and gave scores according to the proportion of health messages/activities provided for the health conditions encountered in households. We aimed to determine (1) messages/activities scores derived from the proportion of health messages given in the households by CHWs who provide comprehensive care in South Africa, and (2) the associated factors.MethodsIn three districts (from two provinces), we trained five fieldworkers to score the messages provided by, and activities of, 34 CHWs that we randomly selected during 376 household visits in 2018 and 2020 using a cross-sectional study designs. Multilevel models were fitted to identify factors associated with the messages/activities scores, adjusted for the clustering of observations within CHWs. The models were adjusted for fieldworkers and study facilities (n = 5, respectively) as fixed effects. CHW-related (age, education level, and phase of CHW training attended/passed) and household-related factors (household size [number of persons per household], number of conditions per household, and number of persons with a condition [hypertension, diabetes, HIV, tuberculosis TB, and cough]) were investigated.ResultsIn the final model, messages/activities scores increased with each extra 5-min increase in visit duration. Messages/activities scores were lower for households with either children/babies, hypertension, diabetes, a large household size, numerous household conditions, and members with either TB or cough. Increasing household size and number of conditions, also lower the score. The messages/activities scores were not associated with any CHW characteristics, including education and training.ConclusionThis study identifies important factors related to the messages provided by and the activities of CHWs across CHW teams. Increasing efforts are needed to ensure that CHWs who provide comprehensive care are supported given the wider range of conditions for which they provide messages/activities, especially in households with hypertension, diabetes, TB/cough, and children or babies.