bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiome characteristics of women with hypothyroidism during early pregnancy detected by 16S rRNA amplicon sequencing and shotgun metagenomic
Authors: Hu Lin , Xu Yajuan , Li Jingjing , Zhang Miao , Sun Zongzong , Ban Yanjie , Tian Xin , Liu Dong , Hu Lulu 
Published: August 2024

ObjectiveThis study aimed to explore the correlation between microbiota dysbiosis and hypothyroidism in early pregnancy by 16S rRNA amplicon sequencing combined with metagenomic sequencing.MethodsSixty pregnant women (30 with hypothyroidism and 30 normal controls) were recruited for 16S rRNA amplicon sequencing, and 6 patients from each group were randomly selected for metagenomic sequencing to assess the gut microbiome profile.ResultsThe 16S rRNA results showed that beta-diversity in the hypothyroidism group was decreased. The relative abundances of the Prevotella and Paraprevotella genera increased in the hypothyroidism group, and Blautia predominated in the controls. The metagenomics results revealed that Prevotella_stercorea_CAG_629, Prevotella_hominis, Prevotella_sp_AM34_19LB, etc. were enriched in the hypothyroidism group at the species level. Functional analysis revealed that the pyridoxal 5’-phosphate synthase pdxT subunit module was decreased, and the short-chain fatty acid (SCFA) transporter and phospholipase/carboxylesterase modules were strongly enriched in the hypothyroidism group. Hypothyroidism patients had increased C-reactive protein (CRP), interleukin-2 (IL-2), IL-4, IL-10, and tumor necrosis factor (TNF)-α levels. The pyridoxal 5’-phosphate synthase pdxT subunit, the SCFA transporter, and the phospholipase/carboxylesterase module were associated with different Prevotella species.ConclusionIn early pregnancy, women with hypothyroidism exhibit microbiota dysbiosis, and Prevotella may affect the metabolism of glutamate, SCFA, and phospholipases, which could be involved in the development of hypothyroidism during pregnancy.
Lower respiratory tract microbiome and lung cancer risk prediction in patients with diffuse lung parenchymal lesions
Authors: Wang Xiaochang , Xiao Tianchi , Lu Mingqing , Wu Zhaoqing , Chen Lingdan , Zhang Zili , Lu Wenju 
Published: August 2024

ObjectiveIn clinical practice, imaging manifestations of diffuse lung parenchymal lesions are common and indicative of various diseases, making differential diagnosis difficult. Some of these lesions are eventually diagnosed as lung cancer.MethodsBecause respiratory microorganisms play an important role in lung cancer development, we searched for microbial markers that could predict the risk of lung cancer by retrospectively analyzing the lower respiratory tract (LRT) microbiome of 158 patients who were hospitalized in the First Affiliated Hospital of Guangzhou Medical University (March 2021–March 2023) with diffuse lung parenchymal lesions. The final diagnosis was lung cancer in 21 cases, lung infection in 93 cases, and other conditions (other than malignancy and infections) in 44 cases. The patient’s clinical characteristics and the results of metagenomic next-generation sequencing of bronchoalveolar lavage fluid (BALF) were analyzed.ResultsBody mass index (BMI) and LRT microbial diversity (Shannon, Simpson, species richness, and Choa1 index) were significantly lower (P&lt; 0.001, respectively) and Lactobacillus acidophilus relative abundance in the LRT was significantly higher (P&lt; 0.001) in patients with lung cancer. The relative abundance of L. acidophilus in BALF combined with BMI was a good predictor of lung cancer risk (area under the curve = 0.985, accuracy = 98.46%, sensitivity = 95.24%, and specificity = 100.00%; P&lt; 0.001).ConclusionOur study showed that an imbalance in the component ratio of the microbial community, diminished microbial diversity, and the presence of specific microbial markers in the LRT predicted lung cancer risk in patients with imaging manifestations of diffuse lung parenchymal lesions.
Investigation and genetic polymorphism analysis of rodents infected with Echinococcus in Ili Prefecture, Xinjiang Uygur Autonomous Region, China
Authors: Wang Bingjie , Zhao Li , Ban Wanli , Zhang Xu , Quan Chenxi , Teliewuhan Munila , He Lixiong , Chen Zhaoyang , Zhang Zhuangzhi 
Published: August 2024

IntroductionAlveolar echinococcosis (AE) is a life-threatening disease in humans caused by the larval stage of Echinococcus multilocularis. Domestic animals, dogs, foxes, and small mammals constitute the circular chain of AE. To evaluate the infection, distribution, and genetic polymorphism of AE in the Ili Prefecture (Nilka, Xinyuan and Zhaosu), we conducted this survey.MethodsIn June and July 2018, 267 small mammals were captured using water-infusion and mousetrap methods. Combined pathogenic and molecular biological methods were used to observe the histopathology of Echinococcus carried by rodents, amplify the mitochondrial nad1 gene of the pathogen, and investigate the genotype and haplotype diversity of Echinococcus in rodents in Ili Prefecture.ResultsMorphological identification revealed that these captured small mammals belonged to three species, with Microtus gregalis being the dominant species (183/267). Pathological and molecular biological results confirmed that E. multilocularis was the pathogen of echinococcosis in small mammals, with an infection rate of 15.73% (42/267). Among the three areas sampled, the highest infection rate of rodents was 25.45% (14/55) in Nilka County. However, there was no significant difference in the infection rates between regions (χ2 = 5.119, p &gt; 0.05). Of the three captured rodent species, M. gregalis had the highest infection rate of 17.49% (32/183), but there was no significant difference in infection rates between the rodent species (χ2 = 1.364, p &gt; 0.05). Phylogenetic analyses showed that the nad1 gene sequences obtained in this study clustered in the same clade as isolates from China. These isolates contained 21 haplotypes (Hap_1-21); Hap_2 was the most common haplotype (9/42). Furthermore, haplotype diversity (0.925 ± 0.027) and nucleotide diversity (0.01139 ± 0.00119) were higher in the Ili Prefecture than in other regions, indicating that population differentiation was high. Tajima’s D and Fu’s Fs tests were negative (p &gt; 0.10), indicating that the population had expanded. The low fixation index (Fst) ranged from 0.00000 to 0.16945, indicating that the degree of genetic differentiation was different among different populations.DiscussionIn summary, Ili Prefecture is a high incidence area of AE, and Microtus spp. may play an important role in the transmission of AE in this area. The results of this study provide basic data for further study of the molecular epidemiology, genetic differences, and control of E. multilocularis in the Ili Prefecture, Xinjiang.
The optimal timing for intervention in patients with ST-segment elevation myocardial infarction and multivessel disease: a systematic review and meta-analysis
Authors: Chen Yi , Li Meng , Wu Yanqing 
Published: August 2024

PurposeThe optimal timing for nonculprit vascular reconstruction surgery in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease (MVD) is still controversial. Our aim was to explore the optimal intervention time for percutaneous coronary intervention (PCI) in STEMI patients who underwent MVD.MethodsThe PubMed/Medline, EMBASE, Cochrane Library, and ClinicalTrials.gov databases were searched from inception to January 1, 2024 for clinical studies comparing immediate multivessel PCI and staged multivessel PCI in patients with STEMI. The primary outcomes were death from any cause, cardiovascular death, noncardiac death, myocardial infarction (MI) and unplanned ischemia-driven revascularization. The secondary outcomes were ischemic stroke, stent thrombosis, renal dysfunction and major bleeding. The risk ratios (RRs) and odds ratios (ORs) were calculated with fixed-effects models and random-effects models, and 95% confidence intervals (CIs) were calculated.FindingsFive randomized trials with 2,782 patients and six prospective observational studies with 3,131 patients were selected for inclusion in this meta-analysis. The staged PCI group had significantly lower pooled RRs for myocardial infarction (0.43, 95% CI = 0.27–0.67; P = 0.0002) and unplanned ischemia-driven revascularization (0.57, 95% CI = 0.41–0.78; P = 0.0004). There were no significant differences in any cause of death, cardiovascular cause of death, or noncardiac cause of death. However, the results of prospective observational studies in the real world indicated that the staged PCI group had significantly lower pooled ORs for all-cause mortality (2.30, 95% CI = 1.22–4.34; P = 0.01), cardiovascular death (2.29, 95% CI = 1.10–4.77; P = 0.03), and noncardiovascular death (3.46, 95% CI = 1.40–8.56; P = 0.007).ImplicationsAccording to our randomized trial analysis, staged multivessel PCI significantly reduces the risk of myocardial infarction and unplanned ischemia-driven revascularization compared to immediate multivessel PCI. There was no significant difference between the two groups in terms of all-cause mortality, cardiovascular mortality, or noncardiovascular mortality risk. However, prospective non-randomized studies suggest there might be a benefit in mortality in the staged PCI group. Therefore, staged multivessel PCI may be the optimal PCI strategy for STEMI patients with MVD.
The causal relationship between antihypertensive drugs and depression: a Mendelian randomization study of drug targets
Authors: Yang Zixian , Li Jinshuai , Huang Peichu , Li Zhichang , He Jianfeng , Cai Dongchun , Lai Yuzheng 
Published: August 2024

BackgroundDepression ranks as a leading contributor to the global disease burden. The potential causal relationship between the use of antihypertensive medications and depression has garnered significant interest. Despite extensive investigation, the nature of this relationship remains a subject of ongoing debate. Therefore, this study aims to evaluate the influence of antihypertensive medications on depression by conducting a Mendelian randomization study focused on drug targets.MethodWe focused on the targets of five antihypertensive drug categories: ACE Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), Calcium Channel Blockers (CCBs), Beta-Blockers (BBs), and Thiazide Diuretics (TDs). We collected single-nucleotide polymorphisms (SNPs) associated with these drug targets from genome-wide association study (GWAS) statistics, using them as proxies for the drugs. Subsequently, we conducted a Mendelian randomization (MR) analysis targeting these drugs to explore their potential impact on depression.ResultsOur findings revealed that genetic proxies for Beta-Blockers (BBs) were associated with an elevated risk of depression (OR [95%CI] = 1.027 [1.013, 1.040], p &lt; 0.001). Similarly, genetic proxies for Calcium Channel Blockers (CCBs) were linked to an increased risk of depression (OR [95%CI] = 1.030 [1.009, 1.051], p = 0.006). No significant associations were identified between the genetic markers of other antihypertensive medications and depression risk.ConclusionThe study suggests that genetic proxies associated with Beta-Blockers (BBs) and Calcium Channel Blockers (CCBs) could potentially elevate the risk of depression among patients. These findings underscore the importance of considering genetic predispositions when prescribing these medications, offering a strategic approach to preventing depression in susceptible individuals.
Analyzing three pedigrees in X-linked Alport syndrome with the presentation of nephrotic syndrome
Authors: Zhang Jian-Hui , Liu Jie , Ruan Dan-Dan , Chen Qian , Yang Jie , Wu Min , Yu Hong-Ping , Liao Li-Sheng , Zheng Xiao-Ling , Luo Jie-Wei , Zhang Li 
Published: August 2024

BackgroundAlport syndrome (AS) is a common cause of end-stage renal disease (ESRD) with various clinical symptoms and incomplete manifestation. Patients with AS and other renal disorders are often misdiagnosed. This study reported three X-linked dominant Alport syndrome (XLAS) pedigrees with nephrotic syndrome (NS) as the predominant phenotype and analyzed COL4A5 gene alterations.MethodsThree Han Chinese XLAS pedigrees were recruited, and clinical phenotypes were obtained. The pre-certified individuals’ peripheral blood DNA was taken, and whole-genome next-generation sequencing (NGS) was performed for candidate genes and mutation screening, followed by NGS or Sanger sequencing of suspected mutant types in participating family members.ResultsBoth probands A and B were diagnosed with NS through biochemical tests, and X-linked Alport syndrome-associated renal injury was diagnosed by renal biopsy. The biopsy revealed focal foamy cells in the renal interstitium, tearing and delamination changes in the glomerular basement membrane, and negative α3 and α5 chains of type IV collagen. Proband C, who was earlier diagnosed with NS, has now advanced to ESRD, along with his mother and proband A’s mother. Genetic sequencing of all three pedigrees identified three mutations, namely, c.5020C&gt;T, c.4435_4445del, and c.1584_1587+6del in the X-linked dominant gene COL4A5 (NM_000495.5). These mutations lead to the production of shortened proteins, potentially impacting the function of COL4A5 and causing pathogenic effects.ConclusionThe novel c.4435_4445del and c.1584_1587+6del mutations not only enrich the spectrum of mutations in the COL4A5 gene but also indicate that carriers of both mutation sites and those with mutation c.5020C&gt;T may present NS as their primary clinical manifestation.
Awareness and acceptability of gut microbiome transfer
Authors: Tweedie-Cullen Ry Yves , Wilson Brooke C. , Derraik José G. B. , Albert Benjamin B. , Opai Keri , Edwards Taygen , O’Sullivan Justin M. , Cutfield Wayne S. 
Published: August 2024

IntroductionGut microbiome transfer (GMT or faecal microbiome transfer) is gaining increasing attention as a potential treatment for a range of medical conditions. However, public awareness and acceptance are not well understood.MethodsTo better understand the public perception of microbiome transfer in New Zealand, we undertook a nationwide online survey. The anonymous survey was designed and distributed between 2022-2023. Inclusion criteria included being aged 16 years or older and a resident of New Zealand. Distribution channels included social media advertising, posters in public areas, e-mail newsletters, and a survey facilitation company.ResultsA total of 2441 completed surveys were analyzed. Most respondents (71%) had tertiary education, 59% were female, with 62% identifying as NZ European, 12% as Māori, and 3% as Pacific peoples. The findings identified a high level of awareness and acceptability, with 76% of respondents having heard of GMT, and 96% indicating they would consider it if proven efficacious for a health condition they had. High levels of acceptance were observed across all ethnicities. Encapsulated oral FMT treatment was the preferred transfer method.DiscussionPrimary concerns related to GMT included the diet, health, and screening of stool donors, as well as the demonstration of safety and efficacy. These findings will help inform health professionals and researchers about the public’s needs and preferences regarding GMT.
Dietary galactose exacerbates autoimmune neuroinflammation via advanced glycation end product-mediated neurodegeneration
Authors: Haase Stefanie , Kuhbandner Kristina , Mühleck Florian , Gisevius Barbara , Freudenstein David , Hirschberg Sarah , Lee De-Hyung , Kuerten Stefanie , Gold Ralf , Haghikia Aiden , Linker Ralf A. 
Published: August 2024

BackgroundRecent studies provide increasing evidence for a relevant role of lifestyle factors including diet in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). While the intake of saturated fatty acids and elevated salt worsen the disease outcome in the experimental model of MS by enhanced inflammatory but diminished regulatory immunological processes, sugars as additional prominent components in our daily diet have only scarcely been investigated so far. Apart from glucose and fructose, galactose is a common sugar in the so-called Western diet.MethodsWe investigated the effect of a galactose-rich diet during neuroinflammation using myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE) as a model disease. We investigated peripheral immune reactions and inflammatory infiltration by ex vivo flow cytometry analysis and performed histological staining of the spinal cord to analyze effects of galactose in the central nervous system (CNS). We analyzed the formation of advanced glycation end products (AGEs) by fluorescence measurements and investigated galactose as well as galactose-induced AGEs in oligodendroglial cell cultures and induced pluripotent stem cell-derived primary neurons (iPNs).ResultsYoung mice fed a galactose-rich diet displayed exacerbated disease symptoms in the acute phase of EAE as well as impaired recovery in the chronic phase. Galactose did not affect peripheral immune reactions or inflammatory infiltration into the CNS, but resulted in increased demyelination, oligodendrocyte loss and enhanced neuro-axonal damage. Ex vivo analysis revealed an increased apoptosis of oligodendrocytes isolated from mice adapted on a galactose-rich diet. In vitro, treatment of cells with galactose neither impaired the maturation nor survival of oligodendroglial cells or iPNs. However, incubation of proteins with galactose in vitro led to the formation AGEs, that were increased in the spinal cord of EAE-diseased mice fed a galactose-rich diet. In oligodendroglial and neuronal cultures, treatment with galactose-induced AGEs promoted enhanced cell death compared to control treatment.ConclusionThese results imply that galactose-induced oligodendrocyte and myelin damage during neuroinflammation may be mediated by AGEs, thereby identifying galactose and its reactive products as potential dietary risk factors for neuroinflammatory diseases such as MS.
The relationship between metabolite mediated immune regulatory imbalance and the occurrence of malignant tumors of bone and articular cartilage: a Mendelian randomization study
Authors: Long Kehan , Gong Ao , Zheng Tengfei , Liu Shoushen , Ying Zhendong , Xiao Cong 
Published: August 2024

BackgroundThis study aims to assess the causal relationship between immune cell characteristics and malignant tumors of bone and articular cartilage, focusing on the mediating role of metabolites. Using Mendelian randomization, we evaluated these relationships based on genetic variations to identify potential biomarkers and therapeutic targets.MethodsA two-sample Mendelian randomization analysis was conducted using GWAS data for immune cell features and 1,400 metabolites to investigate direct and mediating effects. Effective instrumental variables (IVs) were selected, and statistical analyses—including inverse variance weighting (IVW), weighted median, and mode-based methods—were performed using R software. This approach enabled the assessment of direct causal relationships as well as the potential mediating role of metabolites in the association between immune cell features and malignancies.ResultsSignificant causal relationships were identified between 26 immune phenotypes and the risk of malignant tumors of bone and articular cartilage. Notably, the HLA DR+ NK cell phenotype SSC-A showed a positive correlation with the risk of these malignancies. Further analysis revealed causal relationships with 67 metabolites, 38 of which were positively correlated and 29 negatively correlated. Mediation analysis highlighted the role of immune surveillance and metabolic dysregulation in tumor development, as evidenced by the association between the immune phenotype SSC-A on HLA DR+ NK cells and the metabolite 5-hydroxyhexanoate.ConclusionThe findings suggest significant causal relationships between immune phenotypes and malignant tumors of bone and articular cartilage, with metabolites potentially mediating these relationships. These insights lay the groundwork for further research and could contribute to the development of new biomarkers and treatment strategies.
Initial clinical evidence on biperiden as antiepileptogenic after traumatic brain injury—a randomized clinical trial
Authors: Foresti Maira Licia , Garzon Eliana , de Moraes Mariana Teichner , Valeriano Rafael P. S. , Santiago João Paulo , dos Santos Gustavo Mercenas , Longo Natália Mata , Baise Carla , Andrade Joaquina C. Q. F. , Susemihl Maria Alice , Leite Claudia da Costa , Naffah Mazzacoratti Maria da Graça , Paiva Wellingson Silva , de Andrade Almir Ferreira , Teixeira Manuel Jacobsen , Mello Luiz E. 
Published: August 2024

There is currently no efficacious intervention for preventing post-traumatic epilepsy (PTE). Preclinical studies support the potential use of anticholinergics for this condition. The purpose of this study was to evaluate the effects of biperiden as an intervention for preventing PTE. A randomized, double-blinded clinical trial was conducted at HC/FMUSP between 2018–2022. Adults with acute traumatic brain injury (TBI) were randomly assigned to receive biperiden or placebo, for 10 days. The primary outcome was the incidence of PTE while the secondary outcomes included the frequency of seizures, the frequency of any adverse events and mortality after 24 months. The study was powered at a planned enrolment of 132 patients. The trial began in January 2018 and was halted by researchers on March 2020 (and terminated in December 2022) in the face of the global COVID-19 pandemic. Overall, 123 participants were randomized and 112 contributed with data for modified mITT analysis, being that 61 (49.5%) participants completed the 24-month follow-up consult. Data analysis indicated lack of evidence of biperiden for either, the incidence of post-traumatic epilepsy (2.6, 95%CI, 0.65–10.57; p = 0.170) or the mortality rate (1.57, 95%CI, 0.73–3.38; p = 0.248). The frequency of late post-traumatic seizures was higher for biperiden group (2.03, 95%CI = 0.912–3.1597; p &lt;0.001). The present study suggests that there was insufficient evidence regarding the effect of biperiden in preventing PTE after TBI, which underpins the need for larger studies.Clinical trial registration: ClinicalTrials.gov, identifier: NCT01048138.
Stepping into emotions: investigating the effect of angry and fearful faces on forward stepping and quiet stance
Authors: Lebert Angélique , Vilarroya Oscar , Stins John 
Published: August 2024

IntroductionFacial expressions conveying an emotion may affect social interactions, such as approach- or avoidance-related behaviors. A specific facial feature is the gaze direction. An emotional facial expression such as anger will elicit distinct behavioral tendencies, depending on whether the angry gaze is directed toward the onlooker, or in a different direction. We tested whether facial expressions of anger and fear, combined with direct or averted gaze, elicit approach- or avoidance tendencies, using a go/no-go variant of the whole-body stepping task.MethodHealthy adults stood on a force plate, recording the center of pressure (COP). Participants were presented with angry or fearful faces; either with direct or averted gaze. Participants had to identify the emotion, and “depending on instructions- either make a single step forward, or remain in a quiet stance. From the COP of the forward steps, we derived parameters such as reaction time and step size. From the quiet standing trials we derived parameters of postural sway, indicative of postural “freeze.” We used analysis of variance to analyze the outcomes.Results and discussionFirst, we found that steps were initiated faster with angry faces than with fearful faces, in line with existing literature. Second, we did not observe a significant effect of gaze direction. Forward steps with direct and averted gaze had similar COP characteristics. Finally, we had expected to find freeze (postural immobility) with fearful faces, but this was also not observed. We discuss various explanations for the finding, and implications for research into the motoric grounding of social interactions.