bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic arterial infusion chemotherapy plus lenvatinib with or without programmed cell death protein-1 inhibitors for advanced cholangiocarcinoma
Authors: Wei Zhanqi , Wang Yajing , Wu Boyang , Liu Ying , Wang Yaqin , Ren Zhizhong , Yang Xiaowei , Chen Qian , Zhang Yuewei 
Published: August 2023

BackgroundNew treatment strategies are needed to improve outcomes for patients with advanced cholangiocarcinoma (CCA) due to the limited efficacy of current first-line chemotherapy regimens. Although the combination of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and programmed cell death protein-1 (PD-1) inhibitors has been extensively evaluated in the treatment of advanced hepatocellular carcinoma, their roles in advanced CCA remain poorly understood. The purpose of this study is to compare the efficacy and safety of HAIC plus lenvatinib with or without PD-1 inhibitors in patients with advanced CCA.MethodsBetween March 2019 to June 2022, patients diagnosed with advanced CAA who received HAIC plus lenvatinib with or without PD-1 inhibitors treatment were reviewed for eligibility. Efficacy was evaluated according to survival and tumor response, and safety was evaluated according to the incidence of adverse events (AEs).ResultsFifty-five patients with advanced CCA were included in the study, and they were divided into the HAIC+lenvatinib (LEN)+PD-1 inhibitors (PD-1i) group (n = 35) and HAIC+LEN group (n = 20). The median follow-up time was 14.0 (5–42) months. Patients in the HAIC+LEN+PD-1i group had significantly better PFS (HR = 0.390; 95% CI 0.189-0.806; p = 0.001) and OS (HR = 0.461; 95% CI 0.229-0.927; p = 0.01) than those in the HAIC+LEN group. The HAIC+LEN+PD-1i group showed a higher objective response rate and disease control rate than the HAIC+LEN group but did not find a significant difference. The incidence of grade 1-2 and grade 3-4 AEs was not significantly higher in the HAIC+LEN+PD-1i group compared to the HAIC+LEN group, whereas two patients (5.7%) in the HAIC+LEN+PD-1i group experienced grade 5 immune-mediated pneumonia.ConclusionHAIC plus lenvatinib with PD-1 inhibitors is safe and well-tolerated, and has the potential to prolong the survival of patients with advanced CCA. The addition of PD-1 inhibitors may enhance the efficacy of HAIC and lenvatinib. Therefore, the combined therapy has the potential to become a treatment option for advanced CCA.
Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection
Authors: Rosel-Pech Cecilia , Pinto-Cardoso Sandra , Chávez-Torres Monserrat , Montufar Nadia , Osuna-Padilla Iván , Ávila-Ríos Santiago , Reyes-Terán Gustavo , Aguirre-Alvarado Charmina , Matías Juan Norma Angelica , Pérez-Lorenzana Héctor , Vázquez-Rosales José Guillermo , Bekker-Méndez Vilma Carolina 
Published: August 2023

IntroductionOur understanding of HIV-associated gut microbial dysbiosis in children perinatally-infected with HIV (CLWH) lags behind that of adults living with HIV. Childhood represents a critical window for the gut microbiota. Any disturbances, including prolonged exposure to HIV, antiretroviral drugs, and antibiotics are likely to have a significant impact on long-term health, resulting in a less resilient gut microbiome. The objective of our study was to characterize the gut microbiota in CLWH, and compare it with HIV-unexposed and -uninfected children.MethodsWe enrolled 31 children aged 3 to 15 years; 15 were CLWH and 16 were HUU. We assessed dietary patterns and quality; quantified soluble and cellular markers of HIV disease progression by flow cytometry, enzyme-linked immunosorbent and multiplex-bead assays, and profiled the gut microbiota by 16S rRNA sequencing. We explored relationships between the gut microbiota, antibiotic exposure, dietary habits, soluble and cellular markers and host metadata.ResultsChildren had a Western-type diet, their median health eating index score was 67.06 (interquartile range 58.76-74.66). We found no discernable impact of HIV on the gut microbiota. Alpha diversity metrics did not differ between CLWH and HUU. Sex impacted the gut microbiota (R-squared= 0.052, PERMANOVA p=0.024). Male children had higher microbial richness compared with female children. Two taxa were found to discriminate female from male children independently from HIV status: Firmicutes for males, and Bacteroides for females. Markers of HIV disease progression were comparable between CLWH and HUU, except for the frequency of exhausted CD4+ T cells (PD-1+) which was increased in CLWH (p=0.0024 after adjusting for confounders). Both the frequency of exhausted CD4+ and activated CD4+ T cells (CD38+ HLADR+) correlated positively with the relative abundance of Proteobacteria (rho=0.568. false discovery rate (FDR)-adjusted p= 0.029, and rho=0.62, FDR-adjusted p=0.0126, respectively).ConclusionThe gut microbiota of CLWH appears similar to that of HUU, and most markers of HIV disease progression are normalized with long-term ART, suggesting a beneficial effect of the latter on the gut microbial ecology. The relationship between exhausted and activated CD4+ T cells and Proteobacteria suggests a connection between the gut microbiome, and premature aging in CLWH.
Doxycycline PEP can induce doxycycline resistance in Klebsiella pneumoniae in a Galleria mellonella model of PEP
Authors: Kenyon Chris , Gestels Zina , Vanbaelen Thibaut , Abdellati Said , Van Den Bossche Dorien , De Baetselier Irith , Xavier Basil Britto , Manoharan-Basil Sheeba Santhini 
Published: August 2023

BackgroundFour randomized controlled trials have now established that doxycycline post exposure (sex) prophylaxis (PEP) can reduce the incidence of chlamydia and syphilis in men who have sex with men. These studies have concluded that the risk of selecting for antimicrobial resistance is low. We evaluated this risk in vitro and in vivo using a Galleria mellonella infection model.MethodsWe evaluated how long it took for doxycycline resistance to emerge during passage on doxycycline containing agar plates in 4 species – Escherichia coli, Klebsiella pneumoniae, Neisseria gonorrhoeae and Neisseria subflava. We then assessed if K. pneumoniae could acquire resistance to doxycycline (and cross resistance to other antimicrobials) during intermittent exposure to doxycycline in a Galleria mellonella model of doxycycline PEP.ResultsIn our passage experiments, we found that resistance first emerged in K. pneumoniae. By day 7 the K. pneumoniae MIC had increased from 2 mg/L to a median of 96 mg/L (IQR 64–96). Under various simulations of doxycycline PEP in the G. mellonella model, the doxycycline MIC of K. pneumoniae increased from 2 mg/L to 48 mg/L (IQR 48–84). Ceftriaxone and ciprofloxacin MICs increased over ten-fold. Whole genome sequencing revealed acquired mutations in ramR which regulates the expression of the AcrAB-TolC efflux pump.ConclusionDoxycycline PEP can select for doxycycline, ceftriaxone and ciprofloxacin resistance in K. pneumoniae in a G. mellonella model. The emergent ramR mutations were similar to those seen in circulating strains of K. pneumoniae. These findings suggest that we need to assess the effect of doxycycline PEP on resistance induction on a broader range of bacterial species than has hitherto been the case.
Integrative analysis of lysine acetylation-related genes and identification of a novel prognostic model for oral squamous cell carcinoma
Authors: Deng Shi-Zhou , Wu Xuechen , Tang Jiezhang , Dai Lin , Cheng Bo 
Published: August 2023

Introduction: Oral squamous cell carcinoma (OSCC), which accounts for a high proportion of oral cancers, is characterized by high aggressiveness and rising incidence. Lysine acetylation is associated with cancer pathogenesis. Lysine acetylation-related genes (LARGs) are therapeutic targets and potential prognostic indicators in various tumors, including oral squamous cell carcinoma. However, systematic bioinformatics analysis of the Lysine acetylation-related genes in Oral squamous cell carcinoma is still unexplored.Methods: We analyzed the expression of 33 Lysine acetylation-related genes in oral squamous cell carcinoma and the effects of their somatic mutations on oral squamous cell carcinoma prognosis. Consistent clustering analysis identified two lysine acetylation patterns and the differences between the two patterns were further evaluated. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to develop a lysine acetylation-related prognostic model using TCGA oral squamous cell carcinoma datasets, which was then validated using gene expression omnibus (GEO) dataset GSE41613.Results: Patients with lower risk scores had better prognoses, in both the overall cohort and within the subgroups These patients also had “hot” immune microenvironments and were more sensitive to immunotherapy.Disscussion: Our findings offer a new model for classifying oral squamous cell carcinoma and determining its prognosis and offer novel insights into oral squamous cell carcinoma diagnosis and treatment.
Phenotypic characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease in children: a single-center, retrospective study
Authors: Hua Yi , Yan Xuke , Liu Liu , Wang Yilong , Xu Lu , Jiang Peifang , Yuan Zhefeng , Gao Feng 
Published: August 2023

ObjectiveTo analyze the clinical characteristics and follow-up data of children with different clinical phenotypes of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).MethodsThe basic demographic and clinical features, laboratory and imaging examination results, and follow-up data of 74 Chinese children with different phenotypes of MOGAD were retrospectively reviewed and analyzed.ResultsThe male-to-female ratio in this cohort was 1:1.39. The clinical phenotypes of MOGAD included acute disseminated encephalomyelitis (ADEM; n = 37), encephalitis (n = 11), optic neuritis (ON, n = 9), neuromyelitis optica spectrum disorder (NMOSD; n = 9), transverse myelitis (TM; n = 6), leukodystrophy-like manifestations (n = 1), and meningitis (n = 1). The mean age of disease onset was 86 months. The number of leukocytes in the cerebrospinal fluid of patients with ADEM was significantly higher than that in patients with ON but lower than that in patients with TM (p &lt; 0.05). The pathogen detection rate among all patients was 36.5%. Recurrence occurred in 17 patients (23%), with the highest recurrence rate in patients with NMOSD and TM. Patients with recurrence had a significantly higher median age than those without any recurrence (109.00 vs. 82.44 months, p &lt; 0.05). The male-to-female ratio in patients with recurrence was 1:4.67, which differed significantly from that at first onset (p &lt; 0.05).ConclusionThe most common clinical phenotypes of MOGAD in this cohort were ADEM and encephalitis. Recurrence of MOGAD may be related to age and sex, with a higher recurrence rate observed in females. These findings provide a basis for further exploration of the characteristics of different MOGAD phenotypes.
Risk factors and a prediction model for unruptured intracranial aneurysms in patients with ischemic stroke using carotid intima-media thickness and systemic atherosclerosis
Authors: Gao Gaiming , Kang Dezhi , Zhang Jinning , Jiang Zhixian , He Xueyang , Wu Yanyu 
Published: August 2023

BackgroundSystemic atherosclerosis and carotid intima-media thickness (IMT) have been widely used in clinical practice for ischemic stroke; however, little is known about the risk factors for unruptured intracranial aneurysms (UIAs) in patients with ischemic stroke (IS). Therefore, we performed this study to identify the risk factors and construct a prediction model for UIA in patients with IS.MethodsData were retrospectively collected from patients with IS from 2015 to 2022 at the First Hospital of Quanzhou City, Quanzhou, Fujian, China. Risk factors for UIA in patients with IS were identified using a multivariate logistic regression model, and a receiver operating characteristic (ROC) curve was applied to construct the prediction model.ResultsOut of the 122 patients with IS, 52 who presented with UIA (ISUIA) were categorized into the study group and the remaining 70 IS patients without UIA into the control group. Patients in the ISUIA group had lower carotid IMT and carotid artery plaque scores than those in the IS group (P &lt; 0.05). Multivariate analyses found that aspirin use (OR: 12.987; P = 0.031), elevated C-reactive protein (CRP) level (OR: 1.019; P = 0.004), and carotid IMT &gt; 0.09 mm (OR: 0.218; P &lt; 0.001) were significantly associated with the risk of UIA in patients with IS. However, UIA in patients with IS was unaffected by the carotid artery plaque score (P = 0.114). The constricted prediction model based on the abovementioned factors for UIA in IS patients was 0.79 (95% CI: 0.71–0.87).ConclusionThe findings revealed that the risk factors for UIA in patients with IS included aspirin use, elevated CRP level, and smaller carotid IMT, and the predictive value of the prediction model was relatively better.
Relief of post-stroke spasticity with acute vibrotactile stimulation: controlled crossover study of muscle and skin stimulus methods
Authors: Seim Caitlyn , Chen Bingxian , Han Chuzhang , Vacek David , Wu Laura Song , Lansberg Maarten , Okamura Allison 
Published: August 2023

BackgroundPrior work suggests that vibratory stimulation can reduce spasticity and hypertonia. It is unknown which of three predominant approaches (stimulation of the spastic muscle, antagonist muscle, or cutaneous regions) most reduces these symptoms.ObjectiveDetermine which vibrotactile stimulation approach is most effective at reducing spastic hypertonia among post-stroke patients.MethodsSham-controlled crossover study with random assignment of condition order in fourteen patients with post-stroke hand spasticity. All patients were studied in four conditions over four visits: three stimulation conditions and a sham control. The primary outcome measure was the Modified Ashworth Scale, and the secondary outcome measure was the Modified Tardieu Scale measured manually and using 3D motion capture. For each condition, measures of spastic hypertonia were taken at four time points: baseline, during stimulation, after stimulation was removed, and after a gripping exercise.ResultsA clinically meaningful difference in spastic hypertonia was found during and after cutaneous stimulation of the hand. Modified Ashworth and Modified Tardieu scores were reduced by a median of 1.1 (SD = 0.84, p = 0.001) and 0.75 (SD = 0.65, p = 0.003), respectively, during cutaneous stimulation, and by 1.25 (SD = 0.94, p = 0.001) and 0.71 (SD = 0.67, p = 0.003), respectively, at 15 min after cutaneous stimulation. Symptom reductions with spastic muscle stimulation and antagonist muscle stimulation were non-zero but not significant. There was no change with sham stimulation.ConclusionsCutaneous vibrotactile stimulation of the hand provides significant reductions in spastic hypertonia, compared to muscle stimulation.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT03814889.
Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial
Authors: Stockem C.F. , Mellema J.J.J. , van Rhijn B.W.G. , Boellaard T.N. , van Montfoort M.L. , Balduzzi S. , Boormans J.L. , Franckena M. , Meijer R.P. , Robbrecht D.G.J. , Suelmann B.B.M. , Schaake E.E. , van der Heijden M.S. 
Published: August 2023

IntroductionStudies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer.MethodsThe INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response.DiscussionThis is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer.Clinical Trial RegistrationThe INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).
Association of KLK4 rs2235091 polymorphism with susceptibility to dental caries: a systematic review and meta-analysis
Authors: Li Youqin , Zhang Lei , Cen Wen , Yuan Yongping 
Published: August 2023

ObjectiveTo investigate the association between Kallikrein-related peptidase-4 (KLK4) rs2235091 polymorphism and susceptibility to dental caries (DC) by a method of systematic review and meta-analysis.MethodsFour English databases were searched for studies on the correlation between KLK4 rs2235091 polymorphism and susceptibility to DC from inception to April 1, 2023. Data analysis was processed by Stata 15.0 software.ResultsFour articles were eligible, including 848 individuals with caries and 463 controls. The results of pooled analysis showed no significant differences in the five gene models (G vs. A: odds ratio (OR) = 1.14, 95% CI: 0.73–1.79, P = 0.567; GG + GA vs. AA: OR = 1.01, 95% CI: 0.77–1.32, P = 0.489; GG vs. GA + AA: OR = 0.84, 95% CI: 0.57–1.23, P = 0.368; GA vs. AA: OR = 1.06, 95% CI: 0.80–1.41, P = 0.681; GG vs. AA: OR = 1.15, 95% CI: 0.57–2.31, P = 0.690). However, subgroup analysis indicated a statistically significant difference in the dominant (GG + GA vs. AA: OR = 1.74, 95% CI: 1.02–2.96, P = 0.042) gene model in primary dentition, but no significance in allelic, recessive, homozygous and heterozygous models. Besides, in permanent dentition, no significant differences were found among the five genetic models (all P &gt; 0.05).ConclusionKLK4 rs2235091 polymorphism may be associated with susceptibility to DC of pediatric primary dentition, but not with the risk of caries of permanent dentition. Genotype GG + GA may increase susceptibility to DC of pediatric primary dentition. However, considering the limited records enrolled in this review, more trials with larger sample sizes and more rigorous designs are needed to verify the conclusions of this meta-analysis in the future.
Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY202380014.
Reading fluency as the bridge between decoding and reading comprehension in Chinese children
Authors: Hsu Lucy Shih-Ju , Chan Kevin , Ho Connie Suk-Han 
Published: August 2023

PurposeReading fluency has been considered an essential component of reading comprehension, but it is yet to be examined in a reading model in a non-alphabetic writing system. This study investigated whether reading fluency could be identified as a separate construct from decoding and examined the unique role of reading fluency in the Simple View of Reading (SVR).MethodA total of 342 Cantonese-speaking Chinese children in grades 3–5 were recruited to participate in the study. They were assessed on word reading accuracy and fluency, morphological awareness, vocabulary knowledge, and reading comprehension.ResultsThe confirmatory factor analysis results confirmed that reading fluency is a separate factor from decoding, linguistic comprehension, and reading comprehension. Furthermore, the structural equation modeling results revealed that reading fluency is a significant predictor of reading comprehension and a mediator between decoding and reading comprehension in the extended SVR model.ConclusionThe findings extended previous research in alphabetic languages and supported reading fluency as the bridge between decoding and reading comprehension. The present study highlighted the importance of reading fluency in Chinese reading acquisition in a theoretical framework.
Relationship between technology acceptance model, self-regulation strategies, and academic self-efficacy with academic performance and perceived learning among college students during remote education
Authors: Navarro Ricardo , Vega Vanessa , Bayona Hugo , Bernal Victor , Garcia Arlis 
Published: August 2023

IntroductionThe aim of this study was to examine the relationship between the technology acceptance model, self-regulation strategies, and academic self-efficacy with academic performance and perceived learning among college students during remote education.MethodsThe participants were 301 university students from Lima. Structural equation model was used to test the proposed theoretical relationships between the variables. On the one hand, the study sought to explore the relationship between academic self-efficacy and self-regulation strategies with the technology acceptance model. On the other hand, it sought to determine whether the three dimensions of the technology acceptance model are positively related to perceived learning and academic performance.ResultsThe results suggest the importance of improving psychological variables such as self-efficacy and self-regulation strategies to improve the acceptance of technology, which would also improve the academic performance and perceived learning of students in a virtual environment.DiscussionThe discussion highlights the significance of self-efficacy and metacognitive strategies in influencing technology perception and attitudes, ultimately impacting perceived learning and academic performance in virtual education.