bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: Early molecular confirmation and sodium polystyrene sulfonate management of systemic pseudohypoaldosteronism type I
Authors: Alkhatib Einas H. , Bartlett Deirdre , Kanakatti Shankar Roopa , Regier Debra , Merchant Nadia 
Published: January 2024

IntroductionType 1 pseudohypoaldosteronism (PHA) consists of resistance to aldosterone. Neonatal presentation is characterized by salt wasting, hyperkalemia, and metabolic acidosis with high risk of mortality. Type 1 PHA can be autosomal dominant (renal type 1) or autosomal recessive (systemic type 1). Renal PHA type 1 can be feasibly managed with salt supplementation; however, systemic PHA type 1 tends to have more severe electrolyte imbalance and can be more refractory to treatment.Case PresentationWe present a case of a 3-year-old girl with systemic PHA type 1, diagnosed and confirmed molecularly in infancy, who has been successfully managed with sodium polystyrene sulfonate decanted into feeds along with sodium supplementation. On day 5 of life, a full-term female infant presented to the ED for 2 days of non-bloody, non-bilious emesis, along with hypothermia to 94°F. Laboratory results were notable for hyponatremia (Na) of 127, hyperkalemia (K) of 7.9, and acidosis with bicarbonate level of 11.2. Genetic testing ordered within a week of life confirmed PHA type 1 with a homozygous pathogenic frameshift variant in SCNN1A c.575delA (p.Arg192GlyfsX57). Sodium polystyrene sulfonate and feeds were decanted until the age of 16 months, and she was also continued on NaCl supplementation. She was gradually transitioned to directly administered sodium polystyrene sulfonate without any electrolyte issues. She has overall done well after gastrostomy-tube (G-tube) placement without severe hyperkalemia even with several hospitalizations for gastrointestinal or respiratory illnesses.Discussion/ConclusionA treatment approach to systemic PHA and sodium polystyrene sulfonate administration in neonates and infants is described.
Effect of development speed and quality of blastocyst on singleton birthweight in single frozen-thawed blastocyst transfer cycles
Authors: Wang Xue , Xiao YaLing , Sun ZhengYi , Tao Tao 
Published: January 2024

BackgroundAssisted reproductive technology (ART) has revolutionized infertility treatment, leading to a surge in ART-conceived children. Despite its success, ART-born offspring face higher risks of preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). The mechanisms behind these outcomes remain unclear, partly attributed to multiple embryo transfers. Recent advancements advocate single blastocyst transfers for improved outcomes. However, the influence of blastocyst quality and development speed on neonatal outcomes is underexplored.ObjectiveThis study investigated whether blastocyst development speed and quality affect singleton birthweight when the blastocyst is selected for single frozen-thawed blastocyst transfer (FBT).MethodsData from patients who performed an FBT cycle at our center from July 2011 to June 2021 were collected and analyzed. Based on the inclusion and exclusion criteria, 420 single FBT cycles were assessed. The women were divided into four groups, Group A (day 5, good-quality blastocysts), Group B (day 5, non-good-quality blastocysts), Group C (day 6, good-quality blastocysts), and Group D (day 6, non-good-quality blastocysts) according to the developmental speed and quality of the transferred blastocyst.ResultsThe birthweight was relatively the highest in Group A, which developed rapidly and transferred good quality blastocysts. However, no significant difference existed among the groups (P&gt;0.05). The prevalence of premature birth (PTB), low birth weight (LBW), very low birth weight (VLBW), or high birth weight (HBW) was similar among the four groups (P &gt; 0.05). No correlation existed between birth weight and blastocyst development speed or quality after adjusting for possible confounders (P &gt; 0.05 respectively). However, the difference in the proportion of males born among the four groups was significant, especially in Group D, which was significantly lower than that in Group A (adjusted odds ratio = 0.461, 95% confidence interval: 0.230–0.921, P &lt; 0.05).ConclusionsThis retrospective cohort study suggests that the combined effect of blastocyst development speed and quality on neonatal birthweight is insignificant. The transfer of slow-growing, non-good-quality blastocysts increases the chance of a female baby being born.
Late age at first birth is a protective factor for oesophageal cancer and gastro-oesophageal reflux: the evidence from the genetic study
Authors: Su Yani , Xu Yiwei , Hu Yunfeng , Chang Yu , Wu Fangcai , Yang Mingyi , Peng Yuhui 
Published: January 2024

ObjectiveThe primary objective of this research endeavor was to examine the underlying genetic causality between the age at first birth (AFB) and four prevalent esophageal diseases, namely oesophageal obstruction (OO), oesophageal varices (OV), gastro-oesophageal reflux (GOR), and oesophageal cancer (OC).MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to examine the causal association between AFB and four prevalent esophageal disorders. We employed eight distinct MR analysis techniques to evaluate causal relationships, encompassing random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed-effects IVW. The random-effects IVW method served as the primary approach for our analysis. Furthermore, we executed several sensitivity analyses to assess the robustness of the genetic causal inferences.ResultsThe random-effects IVW analysis revealed a significant negative genetic causal association between AFB and both GOR (P &lt; 0.001, Odds Ratio [OR] 95% Confidence Interval [CI] = 0.882 [0.828-0.940]) and OC (P &lt; 0.001, OR 95% CI = 0.998 [0.998-0.999]). Conversely, there was insufficient evidence support to substantiate a genetic causal link between AFB and OO (P = 0.399, OR 95% CI = 0.873 [0.637-1.197]) or OV (P = 0.881, OR 95% CI = 0.978 [0.727-1.314]). The results of sensitivity analyses underscore the robustness and reliability of our MR analysis.ConclusionThe findings of this investigation substantiate the notion that elevated AFB confers a protective effect against GOR and OC. In addition, no causative association was discerned between AFB and OO or OV at the genetic level.
Methylenetetrahydrofolate reductase polymorphic variants C677T and A1298C in rectal cancer in Slavic population: significance for cancer risk and response to chemoradiotherapy
Authors: Stanojevic Aleksandra , Spasic Jelena , Marinkovic Mladen , Stojanovic-Rundic Suzana , Jankovic Radmila , Djuric Ana , Zoidakis Jerome , Fijneman Remond J. A. , Castellvi-Bel Sergi , Cavic Milena 
Published: January 2024

Background: Methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) have been suggested as risk, prognostic, and predictive factors for colorectal cancer in various populations, but have not been validated so far. The aim of this study was to examine the association of MTHFR C677T (rs1801133) and A1298C (rs1801131) single nucleotide polymorphisms with the risk of rectal cancer as well as the response to neoadjuvant chemoradiotherapy (nCRT) based on 5-Fluorouracil (5-FU)/leucovorin (LV) in the locally advanced setting.Patients and methods: This case-control study included 119 healthy controls and 97 patients with locally advanced rectal cancer (LARC). For MTHFR genotyping, restriction fragment length polymorphism analysis (PCR-RFLP) was employed.Results:In silico analysis highlighted that SNPs C677T and A1298T correlate with MTHFR gene expression, and that gene expression profile correlates with cancer risk and stage. Using dominant and recessive models, it was found that the MTHFR 677CC vs. 677CT+677TT have increased risk of cancer development (odds ratio (OR): 2.27; 95% confidence interval (CI): 1.30–3.95, p = 0.002) as well as 677CC+677CT compared to 677TT (OR: 4.18, 95% CI: 1.16–14.99, p = 0.014). MTHFR 1298AA also shown increased risk for cancer development compared to 1298AC+1298CC (OR:2.0, 95% CI: 1.20–3.59, p = 0.035) Statistical analysis of combined genotypes highlighted the protective role of CT/AC combined genotype (OR: 3.15 95% CI: 1.576–6.279, p = 0.002) while the CC/AA genotype showed an increased risk for rectal cancer development (OR: 2.499, 95% CI: 1.246–5.081, p = 0.016) The carriers of the 677C/1298A haplotype had the highest risk for developing rectal cancer (OR: 1.74; 95% CI: 1.198–2.530, p = 0.002) while the 677T/1298C haplotype seems to provide a protective effect. (OR: 0.44; 95%CI 0.248–0.795, p = 0.003). No significant association with response to chemoradiotherapy was found.Conclusion: Our data point to MTHFR 667C allele and 1298A alleles as low-penetrance risk factors for rectal cancer in our population. To the best of our knowledge, this is the first study of this type performed on the Slavic population in the Western Balkan, as various population-based factors might also be significant our findings can be used for future meta-analyses and the construction of genetic cancer risk prediction panels.
Safety and efficacy of biliary stenting combined with iodine-125 seed strand followed by hepatic artery infusion chemotherapy plus lenvatinib with PD-1 inhibitor for the treatment of extrahepatic cholangiocarcinoma with malignant obstructive jaundice
Authors: Lin Long-Wang , Ke Kun , Chen Rong , Yang Wei-Zhu , Huang Ning , Wu Zheng-Zhong 
Published: January 2024

ObjectivesTo evaluate the efficacy and safety of biliary stenting implantation with iodine-125 seed strand (SI) followed by hepatic artery infusion chemotherapy (HAIC) plus lenvatinib (Len) with programmed death-1 (PD-1) inhibitor for patients diagnosed with extrahepatic cholangiocarcinoma (ECC) and malignant obstructive jaundice (MOJ).MethodsIn this single-center retrospective study, the data of ECC patients with MOJ from March 2015 to January 2023 was assessed. Using probability score matching (PSM), the selection bias of patients was reduced. Primary study outcomes included overall survival (OS) and progression-free survival (PFS). The OS and PFS were performed using the Kaplan–Meier method and evaluated with the log-rank test.ResultsA total of 104 patients were enrolled finally, including 52 patients treated with interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor (SI+HAIC+Len+P group) and 52 patients treated with interventional therapy (SI+HAIC) plus lenvatinib (SI+HAIC+Len group). 26 pairs of patients were matched after PSM analysis. After PSM analysis, the median OS and PFS in the SI+HAIC+Len+P group were significantly longer compared to those in the SI+HAIC+Len group (OS:16.6 vs. 12.3 months, P = 0.001; PFS:12.6 vs 8.5 months, P = 0.004). The DCR was significantly different between groups (P = 0.039), while ORR not (P = 0.548). The addition of PD-1 inhibitor was generally well tolerated without treatment-associated mortality.ConclusionInterventional therapy (SI+HAIC) plus Len with PD-1 inhibitor was effective for ECC patients accompanied by MOJ with a manageable safety profile.
Gut microbiota in combination with blood metabolites reveals characteristics of the disease cluster of coronary artery disease and cognitive impairment: a Mendelian randomization study
Authors: Xu Shihan , Liu Yanfei , Wang Qing , Liu Fenglan , Xian Yanfang , Xu Fengqin , Liu Yue 
Published: January 2024

BackgroundThe coexistence of coronary artery disease (CAD) and cognitive impairment has become a common clinical phenomenon. However, there is currently limited research on the etiology of this disease cluster, discovery of biomarkers, and identification of precise intervention targets.MethodsWe explored the causal connections between gut microbiota, blood metabolites, and the disease cluster of CAD combined with cognitive impairment through two-sample Mendelian randomization (TSMR). Additionally, we determine the gut microbiota and blood metabolites with the strongest causal associations using Bayesian model averaging multivariate Mendelian randomization (MR-BMA) analysis. Furthermore, we will investigate the mediating role of blood metabolites through a two-step Mendelian randomization design.ResultsWe identified gut microbiota that had significant causal associations with cognitive impairment. Additionally, we also discovered blood metabolites that exhibited significant causal associations with both CAD and cognitive impairment. According to the MR-BMA results, the free cholesterol to total lipids ratio in large very low density lipoprotein (VLDL) was identified as the key blood metabolite significantly associated with CAD. Similarly, the cholesteryl esters to total lipids ratio in small VLDL emerged as the primary blood metabolite with a significant causal association with dementia with lewy bodies (DLB). For the two-step Mendelian randomization analysis, we identified blood metabolites that could potentially mediate the association between genus Butyricicoccus and CAD in the potential causal links.ConclusionOur study utilized Mendelian randomization (MR) to identify the gut microbiota features and blood metabolites characteristics associated with the disease cluster of CAD combined with cognitive impairment. These findings will provide a meaningful reference for the identification of biomarkers for the disease cluster of CAD combined with cognitive impairment as well as the discovery of targets for intervention to address the problems in the clinic.
Tongbian decoction restores intestinal microbiota and activates 5-hydroxytryptamine signaling: implication in slow transit constipation
Authors: Li Hongjia , Lv Na , Li Dongna , Qian Yunzhi , Si Xianghuan , Hua Yuanqing , Wang Yujuan , Han Xiaojuan , Xu Tianshu 
Published: January 2024

IntroductionSlow transit constipation (STC) is a type of functional constipation. The detailed mechanism of STC, for which there is currently no effective treatment, is unknown as of yet. Tongbian decoction (TBD), a traditional Chinese medicinal formula, is commonly used to treat STC in clinical settings. However, the potential impact of TBD on the management of STC via modulation of the gut microbiota remains unclear.MethodsPseudo-germ-free rats were constructed after 6 days of treatment with bacitracin, neomycin, and streptomycin (abbreviated as ABX forthwith). Based on the successful construction of pseudo-germ-free rats, the STC model (ABX + STC) was induced using loperamide hydrochloride. After successful modeling, based on the different sources of donor rat microbiota, the ABX + STC rats were randomly divided into three groups: Control → ABX + STC, STC → ABX + STC, and STC + TBD → ABX + STC for fecal microbiota transplant (FMT). Body weight, fecal water content, and charcoal power propelling rate of the rats were recorded. Intestinal microbiota was detected by 16S rRNA sequencing, and the 5-hydroxytryptamine (5-HT) signaling pathway was examined by western blots, immunofluorescence, and immunohistochemical analysis.ResultsAfter treatment with fecal bacterial solutions derived from rats treated with Tongbian decoction (TBD), there was an increase in body weight, fecal water content, and the rate of charcoal propulsion in the rats. Additionally, activation of the 5-hydroxytryptamine (5-HT) signaling pathway was observed. The 16S rRNA sequencing results showed that the fecal bacterial solution from TBD-treated rats affected the intestinal microbiota of STC rats by increasing the proliferation of beneficial bacteria and suppressing the expansion of harmful bacteria.ConclusionOur study showed that TBD alleviated constipation in STC rats by modulating the structure of the intestinal microbiota.
Causal relationship between gut microflora and dementia: a Mendelian randomization study
Authors: Fu Jinjie , Qin Yuan , Xiao Lingyong , Dai Xiaoyu 
Published: January 2024

BackgroundNumerous pertinent investigations have demonstrated a correlation between gut microflora (GM) and the occurrence of dementia. However, a causal connection between GM and dementia and its subtypes has not yet been clarified.ObjectiveTo explore the causal association between GM and dementia, including its subtypes, a two-sample Mendelian randomization (TSMR) analysis was used.MethodsOur data comes from the Genome-Wide Association Study (GWAS). The principal approach employed for the Mendelian randomization study was the inverse-variance weighted method, supplemented by four methods: MR-Egger, weighted median, simple mode, and weighted mode. This was followed by Cochrane’s Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out as sensitivity analysis validation.ResultsTwenty-one GMs associated with any dementia, Alzheimer’s disease, vascular dementia, Lewy body dementia, Parkinson’s disease, and dementia under other disease classifications were derived from the analysis, and 21 passed sensitivity tests.ConclusionWe confirmed the causal relationship between GM and dementia and its subtypes, derived specific flora associated with increased or decreased risk of dementia, and provided new ideas for preventive, diagnostic, and therapeutic interventions for dementia mediated by gut microbiota.
Fully synthetic phosphorylated Tau181, Tau217, and Tau231 calibrators for Alzheimer’s disease diagnosis
Authors: Li Xinyu , Zeng Huimei , Durairaj Pradeepraj , Wen Weihuan , Li Tianpeng , Zhao Yanru , Liu Yang , Liu Xue , Zhan Lingpeng , Rao Lang , Yuan Wen , Guo Tengfei , Shen Weijun , Cai Hui , Chen Zhicheng 
Published: January 2024

BackgroundThe calibrator in immunoassay plays an essential role in diagnosing Alzheimer’s disease (AD). Presently, the most well-studied biomarkers for AD diagnosis are three phosphorylated Tau (p-Tau): p-Tau231, p-Tau217, and p-Tau181. Glycogen synthase-3beta (GSK3β)-phosphorated Tau-441 is the most commonly used calibrator for p-Tau immunoassays. However, the batch-to-batch inconsistency issue of the commonly used GSK3β-phosphorylated Tau-441 limits its clinical application.MethodsWe have successfully generated and characterized 61 Tau monoclonal antibodies (mAbs) with distinct epitopes by using the hybridoma technique and employed them as capture or detection antibodies for p-Tau immunoassays. Through chemical synthesis, we synthesized calibrators, which are three peptides including capture and detection antibody epitopes, for application in immunoassays that detect p-Tau231, p-Tau217, and p-Tau181. The novel calibrators were applied to Enzyme-linked immunosorbent assay (ELISA) and Single-molecule array (Simoa) platforms to validate their applicability and establish a range of p-Tau immunoassays.ResultsBy employing the hybridoma technique, 49 mAbs recognizing Tau (1–22), nine mAbs targeting p-Tau231, one mAb targeting p-Tau217, and two mAbs targeting p-Tau181 were developed. Peptides, including recognition epitopes of capture and detection antibodies, were synthesized. These peptides were used as calibrators to develop 60 immunoassays on the ELISA platform, of which six highly sensitive immunoassays were selected and applied to the ultra-sensitive Simoa platform. Remarkably, the LODs were 2.5, 2.4, 31.1, 32.9, 46.9, and 52.1 pg/ml, respectively.ConclusionThree novel p-Tau calibrators were successfully generated and validated, which solved the batch-to-batch inconsistency issue of GSK3β-phosphorylated Tau-441. The novel calibrators exhibit the potential to promote the standardization of clinical AD diagnostic calibrators. Furthermore, we established a series of highly sensitive and specific immunoassays on the Simoa platform based on novel calibrators, which moved a steady step forward in p-Tau immunoassay application for AD diagnosis.
Altered dynamic effective connectivity of the default mode network in type 2 diabetes
Authors: Xu Kun , Wang Jun , Liu Guangyao , Yan Jiahao , Chang Miao , Jiang Linzhen , Zhang Jing 
Published: January 2024

IntroductionAltered functional connectivity of resting-state functional magnetic resonance imaging (rs-fMRI) within default mode network (DMN) regions has been verified to be closely associated with cognitive decline in patients with Type 2 diabetes mellitus (T2DM), but most studies neglected the fluctuations of brain activities—the dynamic effective connectivity (DEC) within DMN of T2DM is still unknown.MethodsFor the current investigation, 40 healthy controls (HC) and 36 T2DM patients have been recruited as participants. To examine the variation of DEC between T2DM and HC, we utilized the methodologies of independent components analysis (ICA) and multivariate granger causality analysis (mGCA).ResultsWe found altered DEC within DMN only show decrease in state 1. In addition, the causal information flow of diabetic patients major affected areas which are closely associated with food craving and metabolic regulation, and T2DM patients stayed longer in low activity level and exhibited decreased transition rate between states. Moreover, these changes related negatively with the MoCA scores and positively with HbA1C level.ConclusionOur study may offer a fresh perspective on brain dynamic activities to understand the mechanisms underlying T2DM-related cognitive deficits.
Exploring the utility of a latent variable as comprehensive inflammatory prognostic index in critically ill patients with cerebral infarction
Authors: Shu Chang , Zheng Chenguang , Zhang Guobin 
Published: January 2024

ObjectiveWe introduce the comprehensive inflammatory prognostic index (CIPI), a novel prognostic tool for critically ill cerebral infarction patients, designed to meet the urgent need for timely and convenient clinical decision-making in this high-risk patient group.MethodsUsing exploratory factor analysis on selected indices—neutrophil to lymphocyte ratio (NLR), systemic inflammation response index (SIRI), and systemic immune inflammation index (SIII)—we derived CIPI, a latent variable capturing their combined predictive power. Data from 1,022 patients in the Medical Information Mart for Intensive Care (MIMIC)-IV database were used to develop CIPI-based survival models, with the robustness and area under the receiver operating characteristic curve (AUC) performance of CIPI validated against an independent dataset of 326 patients from the MIMIC-III CareVue subset. The CIPI’s predictive power for in-hospital and intensive care unit (ICU) mortality was assessed through Kaplan–Meier analysis, univariate and multivariate Cox regression models, and time-dependent AUC analysis. Linearity, subgroup sensitivity analyses and interaction effects with CIPI were also evaluated.ResultsCIPI was an independent prognostic factor, demonstrating a statistically significant association with in-hospital and ICU mortality, when assessed as a continuous and a categorical variable. It showed a linear relationship with mortality rates and demonstrated stability across most subgroups, with no significant interactions observed. Its predictive capabilities for in-hospital and ICU mortality among critically ill cerebral infarction patients matched those of established prognostic indices in the MIMIC database.ConclusionOur study indicates that CIPI is a reliable and effective prognostic tool for critically ill cerebral infarction patients in predicting in-hospital and ICU mortality. Its straightforward calculation, rooted in routine blood tests, enhances its practicality, promising significant utility in clinical settings.