bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acupuncture for hormonal readiness and gut microbiota in obese polycystic ovary syndrome: an open-label, randomized controlled trial
Authors: Wu Tianyu , Xu Guixing , Hong Xiaojuan , Fan Huaying , Zeng Jiuzhi , Liu Yu , Hu Jinqun , Liang Fanrong , Yang Jie , Chen Jiao 
Published: December 2024

ObjectiveTo explore whether acupuncture combined with clomiphene can reduce the luteinizing hormone-to follicle-stimulating hormone ratio and impact the gut microbiota in patients with obese polycystic ovary syndrome.MethodsThis open-label, randomized, parallel-group controlled trial included 86 women aged 20–40 years with obese polycystic ovary syndrome and 19 healthy controls. Participants were randomly assigned to either an acupuncture combined with clomiphene group or a clomiphene-only group, with a healthy control group for comparison. The treatment lasted three menstrual cycles, with acupuncture administered three times weekly and clomiphene given daily from day five of menstruation for five consecutive days per cycle. The primary outcome was the change in the luteinizing hormone-to-follicle-stimulating hormone (LH/FSH) ratio. Secondary outcomes included levels of other sex hormones, glucose and lipid metabolism parameters, self-rating anxiety and depression scale scores, and gut microbiota composition.ResultsIntention-to-treat analysis showed that the adjusted mean luteinizing hormone-to follicle-stimulating hormone ratio decrease was -0.8 (95% CI: -1.14 to -0.46) in the acupuncture combined with clomiphene group and -0.22 (95% CI: -0.47 to 0.01) in the clomiphene group. The adjusted between-group difference was 0.53 (95% CI: 0.24 to 0.82, p &lt; 0.001). The levels of Agathobacter faecis increased, and those of Erysipelatoclostridium spiroforme, Streptococcus lutetiensis, and Lactococcus lactis decreased after acupuncture combined with clomiphene treatment (p &lt; 0.05).ConclusionAcupuncture combined with clomiphene may be safe and effective, reduce the luteinizing hormone-to follicle-stimulating hormone ratio, and improve insulin resistance in obese polycystic ovary syndrome, and these outcomes may be related to the gut microbiota.
Evaluation of the MDM-score system for screening mitochondrial diabetes mellitus in newly diagnosed diabetes patients: a multi-center cohort study in China
Authors: Ma Fuhui , Zhao Jing , Chen Yan , Luo Yunzhi , Du Yuxuan , Li Xia , Xu Tao , Zhou Zhiguang , Zhou Kaixin , Guo Yanying 
Published: December 2024

ObjectiveTo evaluate the performance of MDM-score system in screening for mitochondrial diabetes mellitus (MDM) with m.3243A&gt;G mutation in newly diagnosed diabetes.MethodsFrom 2015 to 2017, we recruited 5130 newly diagnosed diabetes patients distributed in 46 hospitals in China. Their DNA samples were subjected to targeted sequencing of 37 genes, including the mitochondrial m.3243A&gt;G mutation. Based on this cohort, we analyzed the clinical characteristics of MDM and type 2 diabetes (T2DM), and evaluated the overall efficacy of the MDM-score through ROC curve analysis.ResultsMDM patients were diagnosed at a younger age (P =0.002) than T2DM patients. They also had a higher proportion of females, lower body mass index, lower height, lower weight, lower systolic blood pressure, and lower fasting C-peptide (P &lt; 0.05). Among 48 MDM patients, the m.3243A&gt;G heteroplasmy level was higher in MDM score ≥ 3 than in MDM score &lt; 3 (P = 0.0281). There were 23 cases with MDM-score ≥ 3 in clinical T2DM, with an AUC of 0.612 (95% CI: 0.540-0.683, P &lt;0.001) on ROC curve analysis, yielding sensitivity of 47.9%, specificity of 74.4%, positive predictive value of 1.9%, and negative predictive value of 99.3%. This suggests that almost half of MDM patients can be identified by the MDM score system.ConclusionsThe MDM-score is effective for screening MDM in newly diagnosed clinical T2DM, and some metrics may help to improve its performance in the future, thereby assisting clinicians in identifying suitable patients for genetic testing, and preventing misdiagnosis and mismanagement of MDM patients.
Environmental regulation and environmental equality: the role of green finance and the digital economy
Authors: Chen Ziyi , Zhuang Guoya , Li Feifei 
Published: December 2024

IntroductionEnvironmental issues are related to the physical health and welfare level of all human beings, and the mandatory and dominant nature of environmental regulation (ER) effectively solves the difficult problem of unequal environmental obligations and gives impetus to improving environmental equality.MethodsTherefore, based on a sample of 238 prefecture-level cities in China between 2011 and 2020, this paper empirically examines the mechanism and effect of ER intensity on environmental fairness using the Gini coefficient and the Theil index. In addition, this paper further tests the mechanisms of mediating influence and moderating effect of ER on environmental equality.ResultsThe results of the study found that (1) On the basis of mitigating endogenous problems such as adopting instrumental variable strategies, the increase in the intensity of ER has a significant contribution to the realization of environmental equality. (2) ER contributes to the realization of environmental equality through the green innovation transformation effect, which is more pronounced in innovative regions. (3) The level of development of green finance and the digital economy, as an important instrumental approach to promoting sustainable development, can strengthen the path of environmental policy to mitigate environmental inequality.DiscussionThis paper provides suggestions and insights for promoting the implementation of government environmental policies, enhancing the digital transformation of economic development, and promoting the construction of a society-wide green equality system.
A comprehensive analysis of vasculogenic mimicry related genes to predict the survival rate of HCC and its influence on the tumor microenvironment
Authors: Wang Jingyun , Gao Rong , Qi Jian , Xing Yingru , Hong Bo , Wang Hongzhi , Nie Jinfu 
Published: December 2024

ObjectivesInvestigate the predictive value of Vasculogenic mimicry (VM) related genes for the survival and prognosis of Hepatocellular carcinoma (HCC) patients and its role in the tumor microenvironment (TME).MethodsVM-related genes were obtained from previous literature, the expression profiles, single-cell data and clinical information of HCC patients were downloaded from public databases. The HCC patients were divided into different clusters by unsupervised clustering, the differences in prognosis and immune characteristics of VM-related clusters were analyzed. A prognostic model related to VM (VM Score) was constructed based on LASSO regression and univariate and multivariate Cox regression, the correlation between this model and chemotherapy drugs and immunotherapy was studied. Seurat package was used to standardize single-cell data for single-cell level analysis. The expression of risk factors in VM Score was verified by RT-qPCR.ResultsVM Score composed of SPP1, ADAMTS5 and ZBP1 was constructed and validated. VM Score was an independent prognostic factor for HCC. Through the analysis of single cell data further reveals the VM Score influence on TME. In addition, VM Score could provide ideas for the selection of immunotherapy and chemotherapy drugs. RT-qPCR showed that the expression of risk factors was different in HCC cell lines.ConclusionOur results suggest that VM Score may serve as a promising prognostic biomarker for HCC and provide new ideas for immunotherapy in HCC patients.
Comparing newly developed SNP barcode panels with microsatellites to explore population genetics of malaria parasites in the Peruvian Amazon
Authors: Cabrera-Sosa Luis , Safarpour Mahdi , Kattenberg Johanna Helena , Ramirez Roberson , Vinetz Joseph M. , Rosanas-Urgell Anna , Gamboa Dionicia , Delgado-Ratto Christopher 
Published: December 2024

IntroductionMalaria molecular surveillance (MMS) can provide insights into transmission dynamics, guiding national control programs. We previously designed AmpliSeq assays for MMS, which include different traits of interest (resistance markers and pfhrp2/3 deletions), and SNP barcodes to provide population genetics estimates of Plasmodium vivax and Plasmodium falciparum parasites in the Peruvian Amazon. The present study compares the genetic resolution of the barcodes in the AmpliSeq assays with widely used microsatellite (MS) panels to investigate population genetics of Amazonian malaria parasites.MethodsWe analyzed 51 P. vivax and 80 P. falciparum samples from three distinct areas in the Loreto region of the Peruvian Amazon: Nueva Jerusalén (NJ), Mazan (MZ), and Santa Emilia (SE). Population genetics estimates and costs were compared using the SNP barcodes (P. vivax: 40 SNPs and P. falciparum: 28 SNPs) and MS panels (P. vivax: 16 MS and P. falciparum: 7 MS).ResultsThe P. vivax genetic diversity (expected heterozygosity, He) trends were similar for both markers: HeMS = 0.68–0.78 (p &gt; 0.05) and HeSNP = 0.36–0.38 (p &gt; 0.05). P. vivax pairwise genetic differentiation (fixation index, FST) was also comparable: FST-MS = 0.04–0.14 and FST-SNP = 0.03–0.12 (pairwise p &gt; 0.05). In addition, P. falciparum genetic diversity trends (HeMS = 0–0.48, p &lt; 0.05; HeSNP = 0–0.09, p &lt; 0.05) and pairwise FST comparisons (FST-MS = 0.14–0.65, FST-SNP = 0.19–0.61, pairwise p &gt; 0.05) were concordant between both panels. For P. vivax, no geographic clustering was observed with any panel, whereas for P. falciparum, similar population structure clustering was observed with both markers, assigning most parasites from NJ to a distinct subpopulation from MZ and SE. We found significant differences in detecting polyclonal infections: for P. vivax, MS identified a higher proportion of polyclonal infections than SNP (69% vs. 33%, p = 3.3 × 10−5), while for P. falciparum, SNP and MS detected similar rates (46% vs. 31%, p = 0.21). The AmpliSeq assay had a higher estimated per-sample cost compared to MS ($183 vs. $27–49).DiscussionThe SNP barcodes in the AmpliSeq assays offered comparable results to MS for investigating population genetics in P. vivax and P. falciparum populations, despite some discrepancies in determining polyclonality. Given both panels have their respective advantages and limitations, the choice between both should be guided by research objectives, costs, and resource availability.
Magnitude of non-communicable disease screening and factors associated with awareness among reproductive age women in Gofa and Basketo zones, Southern Ethiopia: a community-based cross-sectional study
Authors: Domba Markos Manote , Argefa Terefe Gelibo , Gizaw Abraham Tamirat , Bitew Abewa Kebede 
Published: December 2024

BackgroundThe burden of non-communicable diseases (NCDs) increasing at an alarming rate in Ethiopia. NCDs affect reproductive-age women and cause significant threats to future generations. Screening is an important aspect leading to early diagnosis, treatment and preventing the risk of complications and future mortality. However, less attention has been paid in the post-pandemic era of COVID-19. Therefore, this study aims to assess awareness of NCD screening and associated factors among reproductive-age women in the Gofa and Basketo zones.MethodsA community-based cross-sectional study design was undertaken, employing a multistage cluster sampling method to select participants from the designated zones. Multivariate logistic regression was conducted using Statistical Package for the Social Sciences (SPSS) software. Associations were deemed statistically significant if the p-value was ≤0.05.ResultsThe awareness level for screening NCDs among women was found to be 54.8%. Specifically, the percentages for awareness of hypertension (HTN), diabetes, cervical cancer, and breast cancer screenings were 52.7%, 42.4%, 38.1%, and 34.8% respectively. However, the study revealed that only 43.0%, 9.4%, 16.2%, and 20.7% of the participants had undergone screening for HTN, diabetes, breast cancer, and cervical cancer respectively. High awareness of NCD screening was significantly associated with urban residence (AOR: 1.68, 95% CI: 1.63, 1.73), Gofa zone residence (AOR: 2.04, 95% CI: 1.95, 2.13), being able to read and write (AOR: 1.06, 95% CI: 1.02, 1.11), having primary (AOR: 1.13, 95% CI: 1.09, 1.16) and secondary school education (AOR: 1.11, 95% CI: 1.00, 1.14), being in the age group of 25–34 (AOR: 1.45, 95% CI: 1.41, 1.49) and ≥35 years (AOR: 1.22, 95% CI: 1.18, 1.26), being married (AOR: 1.25, 95% CI: 1.16, 1.35) and single women (AOR: 1.31, 95% CI: 1.18, 1.43), government employees (AOR: 1.65, 95% CI: 1.54, 1.77), having larger family sizes (&gt;4) (AOR: 1.11, 95% CI: 1.05, 1.12) and having a family member diagnosed with NCD (AOR: 1.16, 95% CI: 1.11, 1.22).ConclusionsNearly half of the study population had no awareness of NCD screening and the vast majority had poor screening practice. Strengthening the provision of behavioral change communication strategies through trained health professionals based on the audience's segmentation by age, educational and economic status is needed.
Effects of prolonged oxytetracycline supplementation on freshwater stinging catfish (Heteropneustes fossilis): a multi-biomarker approach
Authors: Choudhary Pushpa , Naik Saisweta P. , Sahoo Sameer Ranjan , Das Rakesh , Sahoo Satya Narayan , Panda Satyen Kumar , Abraham Thangapalam Jawahar , Patil Prasanna Kumar , Swain Priyabrat , Mishra Sudhansu Sekhar 
Published: December 2024

BackgroundAquaculture systems that sporadically depend on antibiotics can contribute to the development of adverse effects on the fish, microbial flora and the environment. This study sought to investigate the impacts of extended oxytetracycline supplementation on the freshwater stinging catfish Heteropneustes fossilis through a multi-biomarker approach.MethodsA total of 300 H. fossilis (20 ± 0.5 g) were placed in fibreglass-reinforced plastic tanks. The experimental fish were administered oxytetracycline hydrochloride (OTC) at varying doses, viz., 80 mg/kg fish biomass/day (1x), 240 mg (3x), 400 mg (5x), and 800 mg (10x) for 30 consecutive days. The study also included a control group that did not receive OTC.ResultsOTC was effective against Aeromonas hydrophila, Pseudomonas putida, and Plesiomonas shigelloides, with minimum inhibitory concentrations ranging between 0.5 and 8.0 µg/mL. The OTC supplementation retarded the growth of fish. The respiratory burst activity, myeloperoxidase, and lysozyme increased significantly in the 1x group until day 20. This group showed an increase in serum albumin, whereas other OTC groups exhibited elevated levels of liver functional enzymes, including alanine transaminase, aspartate aminotransferase, and alkaline phosphatase. In addition, OTC groups exhibited increased levels of antioxidant enzymes. The magnitude of the increase was dose- and time-dependent. The liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) study signified a dose-dependent increase in OTC residues in the muscle. After a 10-day discontinuation of OTC, the tissue level retention of residues was minimal in the muscle, specifically in the 1x group compared to other groups. Significant histological alterations were noted in the liver tissues of the 5x and 10x groups, possibly due to oxidative stress and residue accretion.ConclusionThe therapeutic dose of 80 mg/kg biomass/day was safe and tolerated well by H. fossilis, and may be used for sustainable catfish farming practices.
MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity
Authors: Grewe Ilka , Friedrich Monika , Dieck Marie-Louise , Spohn Michael , Ly My Linh , Krähling Verena , Mayer Leonie , Mellinghoff Sibylle C. , Rottstegge Monika , Kraemer Rebekka , Volz Asisa , Becker Stephan , Fathi Anahita , Dahlke Christine , Weskamm Leonie M. , Addo Marylyn M. 
Published: December 2024

IntroductionVaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity. Integrating data on both innate and adaptive immunity, systems vaccinology approaches can improve the understanding of vaccine-induced immune mechanisms.MethodsTwo vaccine candidates against SARS-CoV-2, both based on the viral vector Modified Vaccinia virus Ankara (MVA) and encoding the native (MVA-SARS-2-S) or prefusion-stabilized spike protein (MVA-SARS-2-ST), were evaluated in phase 1 clinical trials (ClinicalTrials.gov: NCT04569383, NCT04895449). Longitudinal dynamics of innate and early adaptive immune responses induced by vaccination in SARS-CoV-2-naïve individuals were analyzed based on transcriptome and flow cytometry data, in comparison to the licensed ChAd and mRNA vaccines.ResultsCompared to MVA-SARS-2-S, MVA-SARS-2-ST (encoding the prefusion-stabilized spike protein) induced a stronger transcriptional activation early after vaccination, as well as higher virus neutralizing antibodies. Positive correlations were observed between innate and adaptive immune responses induced by a second MVA-SARS-2-ST vaccination. MVA-, ChAd- and mRNA-based vaccines induced distinct immune signatures, with the overall strongest transcriptional activation as well as monocyte and circulating T follicular helper (cTFH) cell responses induced by ChAd.DiscussionOur findings suggest a potential impact of the spike protein conformation not only on adaptive but also on innate immune responses. As indicated by positive correlations between several immune parameters induced by MVA-SARS-2-ST, the distinct transcriptional activation early after vaccination may be linked to the induction of classical monocytes and activation of cTFH1 cells, which may in turn result in the superior adaptive immunogenicity of MVA-SARS-2-ST, compared to MVA-SARS-2-S. Overall, our data demonstrate that both the vaccine platform and antigen insert can affect innate immune responses and subsequent vaccine immunogenicity in humans.
Dissecting the functions and regulatory mechanisms of disulfidoptosis-related RPN1 in pan-cancer: modulation of immune microenvironment and cellular senescence
Authors: Qin Lexin , Liang Tingting , Zhang Hailong , Gong Xian , Wei Meidan , Song Xiangrong , Hu Yaoyu , Zhu Xinyu , Hu Wentao , Li Jianxiang , Wang Jin 
Published: December 2024

IntroductionCancer’s inherent heterogeneity, marked by diverse genetic and molecular alterations, presents significant challenges for developing effective treatments. One such alteration is the regulation of disulfidoptosis, a recently discovered programmed cell death pathway. RPN1, a key regulator associated with disulfidoptosis, may influence various aspects of tumor biology, including immune evasion and cellular senescence. This study aims to dissect the role of RPN1 in pan-cancer and its potential as a therapeutic target.MethodsWe employed a pan-cancer analysis to explore RPN1 expression and its association with clinical outcomes across multiple tumor types. Immune cell infiltration and expression of immune checkpoint genes were analyzed in relation to RPN1. Additionally, cellular senescence markers were assessed in RPN1 knockdown tumor cells. Gene regulatory mechanisms were studied through gene copy number variations, DNA methylation analysis, and transcriptional regulation by SP1.ResultsRPN1 is overexpressed in a wide range of tumor types and correlates with poor clinical outcomes, including overall survival, disease-specific survival, and progression-free intervals. Our analysis shows that RPN1 is involved in immune evasion, correlating with the presence of myeloid dendritic cells, macrophages, and tumor-associated fibroblasts, and influencing T-cell activity. RPN1 knockdown led to reduced tumor cell proliferation and induced cellular senescence, marked by increased senescence-associated biomarkers and β-galactosidase activity. RPN1 expression was found to be regulated by gene copy number variations, reduced DNA methylation, and transcriptional control via SP1.DiscussionThese findings highlight RPN1 as a key pan-cancer regulator, influencing immune microenvironment interactions and cellular senescence. The regulation of disulfidoptosis by RPN1 presents a promising avenue for therapeutic intervention. Targeting RPN1 could enhance immunotherapy efficacy and help mitigate tumor progression, offering a potential strategy for cancer treatment.
Decreased neuronal excitability in hypertriglyceridemia hamsters with acute seizures
Authors: Shen Qiuyue , Liu Nana , Jiang Yuwu , Liu Lili , Hou Xinlin 
Published: December 2024

IntroductionNeonatal seizures are the most common clinical manifestation of neurological dysfunction in newborns, with an incidence ranging from 1 to 5‰. However, the therapeutic efficacy of current pharmacological treatments remains suboptimal. This study aims to utilize genetically modified hamsters with hypertriglyceridaemia (HTG) to investigate the effects of elevated triglycerides on neuronal excitability and to elucidate the underlying mechanisms. The ultimate goal is to identify novel therapeutic targets for the treatment of neonatal seizures.MethodsAcute seizure models were established both in vivo and ex vivo using wild-type and Apolipoprotein C2 knockout (Apoc2−/−) hamsters. The frequency of tonic–clonic seizures was recorded. Excitatory postsynaptic potentials (EPSPs) and evoked action potentials (eAPs) of pyramidal neurons in the frontal cortex were measured. Fatty acid metabolomic analysis was conducted on microdialysate from the frontal cortex tissue post-seizure, and mRNA expression changes were also assessed.ResultsApoc2−/− hamsters exhibited a reduced frequency of tonic–clonic seizures and diminished EPSP and eAP in comparison to wild-type hamsters. Following seizure induction, free palmitic acid levels in the frontal cortex dialysate significantly decreased, while the expression of palmitoyl acyltransferase 14 (ZDHHC14) in the frontal cortex tissue was higher in Apoc2−/− hamsters than in wild-type hamsters. Additionally, the amplitude of transient outward potassium currents (IA) in cortical neurons of Apoc2−/− hamsters was observed to be elevated compared to wild-type hamsters.ConclusionHypertriglyceridemic Apoc2−/− hamsters exhibited reduced seizure frequency and decreased cortical neuron excitability. The upregulation of ZDHHC14, leading to increased IA, may be a crucial mechanism underlying the observed seizure protection.