bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orally administrated Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 can restore the vaginal health of patients recovering from bacterial vaginosis
Authors: Qi Fengyuan , Fan Shangrong , Fang Chao , Ge Lan , Lyu Jinli , Huang Zhuoqi , Zhao Shaowei , Zou Yuanqiang , Huang Liting , Liu Xinyang , Liang Yiheng , Zhang Yongke , Zhong Yiyi , Zhang Haifeng , Xiao Liang , Zhang Xiaowei 
Published: July 2023

Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and &lt; 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores &lt; 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.
NR2F6, a new immune checkpoint that acts as a potential biomarker of immunosuppression and contributes to poor clinical outcome in human glioma
Authors: Miftah Hayat , Naji Oumayma , Ssi Saadia Ait , Ghouzlani Amina , Lakhdar Abdelhakim , Badou Abdallah 
Published: July 2023

IntoroductionNuclear receptor subfamily 2 group F member 6 (NR2F6) is a promising checkpoint target for cancer immunotherapy. However, there has been no investigation of NR2F6 in glioma. Our study systematically explored the clinical characteristics and biological functions of NR2F6 in gliomas.MethodsWe extracted RNA sequencing (RNA-seq) data of 663 glioma samples from The Cancer Genome Atlas (TCGA) as the training cohort and 325 samples from the Chinese Glioma Genome Atlas (CGGA) as the validation cohort. We also confirmed the NR2F6 gene expression feature in our own cohort of 60 glioma patients. R language and GraphPad Prism softwares were mainly used for statistical analysis and graphical work.ResultsWe found that NR2F6 was significantly related to high tumor aggressiveness and poor outcomes for glioma patients. Functional enrichment analysis demonstrated that NR2F6 was associated with many biological processes that are related to glioma progression, such as angiogenesis, and with multiple immune-related functions. Moreover, NR2F6 was found to be significantly correlated with stromal and immune infiltration in gliomas. Subsequent analysis based on Gliomas single-cell sequencing datasets showed that NR2F6 was expressed in immune cells, tumor cells, and stromal cells. Mechanistically, results suggested that NR2F6 might act as a potential immunosuppression-mediated molecule in the glioma microenvironment through multiple ways, such as the recruitment of immunosuppressive cells, secretion of immunosuppressive cytokines, M2 polarization of macrophages, in addition to combining with other immune checkpoint inhibitors.ConclusionOur findings indicated that intracellular targeting of NR2F6 in both immune cells and tumor cells, as well as stromal cells, may represent a promising immunotherapeutic strategy for glioma. Stromal cells, may represent a promising immunotherapeutic strategy for glioma.
Effects of ranitidine and nizatidine on the risk of gastrointestinal cancer
Authors: Kang Hyejung , Nam Chung Mo , Choi Dong-Woo , Park Sohee 
Published: July 2023

PurposeGastrointestinal (GI) cancer occurs in digestive organs such as the stomach, colon, liver, esophagus, and pancreas. About 83,034 cases occurred in Korea alone in 2020. Dietary factors, alcohol consumption, Helicobacter pylori (H. pylori), and lifestyle factors increase the incidence of diseases such as gastritis, peptic ulcer, pancreatitis, and gastroesophageal reflux disease (GERD), which can develop into GI cancer. However, in 2019, the US Food and Drug Administration announced that the drugs ranitidine and nizatidine, which are used for digestive disorders, contain carcinogens. In this study, we investigated the effects of ranitidine and nizatidine on the development of GI cancer.Materials and methodsIn this study, using National Health Insurance Service–National Sample Cohort (NHIS-NSC) version 2.5 (updated from 2002 to 2019), subjects who developed GI cancer were enrolled in the case group, and those who were at risk of, but did not develop, cancer were enrolled in the control group. Thereafter, risk-set matching was performed (1:3 ratio) by sex and age at the time of diagnosis of cancer in the case group. Through this procedure, 22,931 cases and 68,793 controls were identified. The associations of ranitidine and/or nizatidine with GI cancer were confirmed by adjusted odds ratios (aORs) and 95% confidence intervals (CIs) calculated through conditional logistic regression analysis.ResultsThe aORs of ranitidine and/or nizatidine users were lower than those of nonusers in all average prescription days groups (&lt; 30 days/year: aOR [95% CI] = 0.79 [0.75-0.82]; 30–59 days/year: aOR [95% CI] = 0.66 [0.59-0.73]; 60–89 days/year: aOR [95% CI] = 0.69 [0.59-0.81]; ≥ 90 days/year: aOR [95% CI] = 0.69 [0.59-0.79]). Sensitivity analyses were conducted with different lag periods for the onset of GI cancer after drug administration, and these analyses yielded consistent results. Additional analyses were also performed by dividing subjects into groups based on cancer types and CCI scores, and these analyses produced the same results.ConclusionOur study, using nationwide retrospective cohort data, did not find evidence suggesting that ranitidine and nizatidine increase the risk of GI cancer. In fact, we observed that the incidence of GI cancer was lower in individuals who used the drugs compared to nonusers. These findings suggest a potential beneficial effect of these drugs on cancer risk, likely attributed to their ability to improve digestive function.
U-CHANGE Project: a multidimensional consensus on how clinicians, patients and caregivers may approach together the new urothelial cancer scenario
Authors: Bracarda Sergio , Iacovelli Roberto , Baldazzi Valentina , Zucali Paolo Andrea , Gernone Angela , Conti Giario Natale , Pappagallo Giovanni , Brunelli Matteo , Bruzzi Paolo , Fiorini Edoardo , Magenta Laura , Diomede Francesco , Mereta Federico , D’Aria Irma , Magliano Danilo , Liberatori Monica , Cantù Daniela , Croce Davide , Eandi Simone , Colombo Giorgio Lorenzo , Ferrante Fulvio , Salè Emanuela Omodeo , Marinozzi Andrea , Lenzi Daniele , Remiddi Francesca , Remiddi Stefano 
Published: July 2023

IntroductionAdvanced urothelial carcinoma remains aggressive and very hard to cure, while new treatments will pose a challenge for clinicians and healthcare funding policymakers alike. The U-CHANGE Project aimed to redesign the current model of care for advanced urothelial carcinoma patients to identify limitations (“as is” scenario) and recommend future actions (“to be” scenario).MethodsTwenty-three subject-matter experts, divided into three groups, analyzed the two scenarios as part of a multidimensional consensus process, developing statements for specific domains of the disease, and a simplified Delphi methodology was used to establish consensus among the experts.ResultsRecommended actions included increasing awareness of the disease, increased training of healthcare professionals, improvement of screening strategies and care pathways, increased support for patients and caregivers and relevant recommendations from molecular tumor boards when comprehensive genomic profiling has to be provided for appropriate patient selection to ad hoc targeted therapies.DiscussionWhile the innovative new targeted agents have the potential to significantly alter the clinical approach to this highly aggressive disease, the U-CHANGE Project experience shows that the use of these new agents will require a radical shift in the entire model of care, implementing sustainable changes which anticipate the benefits of future treatments, capable of targeting the right patient with the right agent at different stages of the disease.
Linked-read based analysis of the medulloblastoma genome
Authors: Zwaig Melissa , Johnston Michael J. , Lee John J.Y. , Farooq Hamza , Gallo Marco , Jabado Nada , Taylor Michael D. , Ragoussis Jiannis 
Published: July 2023

IntroductionMedulloblastoma is the most common type of malignant pediatric brain tumor with group 4 medulloblastomas (G4 MBs) accounting for 40% of cases. However, the molecular mechanisms that underlie this subgroup are still poorly understood. Point mutations are detected in a large number of genes at low incidence per gene while the detection of complex structural variants in recurrently affected genes typically requires the application of long-read technologies.MethodsHere, we applied linked-read sequencing, which combines the long-range genome information of long-read sequencing with the high base pair accuracy of short read sequencing and very low sample input requirements.ResultsWe demonstrate the detection of complex structural variants and point mutations in these tumors, and, for the first time, the detection of extrachromosomal DNA (ecDNA) with linked-reads. We provide further evidence for the high heterogeneity of somatic mutations in G4 MBs and add new complex events associated with it.DiscussionWe detected several enhancer-hijacking events, an ecDNA containing the MYCN gene, and rare structural rearrangements, such a chromothripsis in a G4 medulloblastoma, chromoplexy involving 8 different chromosomes, a TERT gene rearrangement, and a PRDM6 duplication.
Two pediatric patients with hemiplegic migraine presenting as acute encephalopathy: case reports and a literature review
Authors: Xiang Yu , Li Fei , Song Zhenfeng , Yi Zhi , Yang Chengqing , Xue Jiao , Zhang Ying 
Published: July 2023

IntroductionHemiplegic migraine (HM) is a rare subtype of migraine. HM in children may be atypical in the initial stage of the disease, which could easily lead to misdiagnosis.MethodsWe report two cases of atypical hemiplegic migraine that onset as an acute encephalopathy. And a comprehensive search was performed using PubMed, Web of Science, and Scopus. We selected only papers that reported complete clinical information about the patients with CACNA1A or ATP1A2 gene mutation.ResultsPatient #1 showed a de novo mutation, c.674C&gt;A (p. Pro225His), in exon 5 of the CACNA1A gene. And patient #2 showed a missense mutation (c.2143G&gt;A, p. Gly715Arg) in exon 16 of the ATP1A2. Together with our two cases, a total of 160 patients (73 CACNA1A and 87 ATP1A2) were collected and summarized finally.DiscussionAcute encephalopathy is the main manifestation of severe attacks of HM in children, which adds to the difficulty of diagnosis. Physicians should consider HM in the differential diagnosis of patients presenting with somnolence, coma, or convulsion without structural, epileptic, infectious, or inflammatory explanation. When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis and treatment. Early recognition and treatment of the disease can help improve the prognosis.
Pneumonia, lymphocytes and C-reactive protein are valuable tests for predicting surgical intervention in necrotizing enterocolitis
Authors: Yu Daiyue , Yang Huirong , Zhong Chen , Fan Kaisi , Zeng Guichang , Zhang Mengzhen , Zhao Qianyun , Yang Jiaming , Yang Liucheng , Wu Kai 
Published: July 2023

BackgroundNecrotizing enterocolitis (NEC) is one of the important causes of neonatal death, and proper timing of operation is of critical significance. This study aimed to explore the high-risk factors for NEC requiring surgical intervention and to provide a reference for its clinical diagnosis and treatment.MethodsClinical and radiological evidence of NEC neonates admitted to Zhujiang Hospital of Southern Medical University and Zhongshan Boai Hospital from January 2010 to October 2022 were retrospectively analyzed. Patients were divided into surgical group and conservative group according to whether they underwent surgery or not. Univariate analysis of the clinical data of the two groups was conducted, and multivariate logistic regression analysis was then performed for statistically significant results in the univariate analysis.Results267 infants were included in this study, of which 90 patients underwent surgical intervention for NEC and 177 conservation treatment. The univariate analysis showed that the gestational age, pneumonia, leukocytes, lymphocytes, erythrocytes, platelets, C-reactive protein, and blood glucose were statistically significant in the surgical group compared to the conservative group (All P &lt; 0.05). Furthermore, the results of multivariate logistic regression analysis showed that compared to the conservative group, patients in the surgical group had a higher proportion of pneumonia (OR = 2.098; 95% CI: 1.030-4.272; P = 0.041), lower lymphocyte values (OR = 0.749; 95% CI: 0.588-0.954; P = 0.019), and higher C-reactive protein values (OR = 1.009; 95% CI: 1.003-1.016; P = 0.004).ConclusionsPneumonia, decreased lymphocytes, and elevated C-reactive protein are potential high-risk factors for neonates with NEC requiring surgical intervention and may have potential clinical implications for predicting surgical risk.
A frequent CYP2D6 variant promotes skipping of exon 3 and reduces CYP2D6 protein expression in human liver samples
Authors: Collins Joseph M. , Lester Hannah , Shabnaz Samia , Wang Danxin 
Published: July 2023

CYP2D6 is one of the most polymorphic drug-metabolizing enzymes in the liver. While genetic CYP2D6 variants serve as clinical biomarkers to predict CYP2D6 activity, large inter-person variability in CYP2D6 expression remains unaccounted for. Previous results suggest that there is variable expression of a CYP2D6 splice isoform with an in-frame deletion of exon 3 (CYP2D6ΔE3) encoding a protein lacking numerous active site residues. Here, using fragment analysis and RT-qPCR, we revealed that rs1058164 G (MAF = 27%–43%) is associated with increased formation of CYP2D6∆E3 in human liver samples (1.4–2.5-fold) and transfected cells. Furthermore, western blots showed that rs1058164 G was associated with a 50% decrease in full-length hepatic CYP2D6 protein expression. In addition, by studying a larger liver cohort, we confirmed our previous results that rs16947 (CYP2D6*2) reduces full-length CYP2D6 mRNA by increasing the production of an unstable splice isoform lacking exon 6 (CYP2D6ΔE6) and that the impact of CYP2D6ΔE6 is offset in carriers of the downstream enhancer variant rs5758550. The three frequent SNPs (rs1058164, rs16947, and rs5758550) form various 3-SNP-haplotypes, each with distinct CYP2D6 expression characteristics. Using an expression score (ES) system, we tested the impact of the 3-SNP-haplotype on improving the standard model to predict hepatic CYP2D6 protein expression based on genotype. A model that incorporates the 3-SNP-haplotype provided the best fit for CYP2D6 expression and also accounted for more variability in CYP2D6 protein levels (59%) than a model based on the accepted standard (36%) or one that only adds rs16947 and rs5758550 (42%). Clinical studies are needed to determine whether including the 3-SNP-haplotype alongside current standard CYP2D6 models improves the predictive value of CYP2D6 panels.
The optimal oxytocin infusion rate for preventing uterine atony during cesarean delivery in elderly parturients with prior history of cesarean delivery
Authors: Wang Li Ying , Wang Jin , Dong Jin Hua , Ping Ze Peng , Chen Xin Zhong , Wei Chang Na 
Published: July 2023

Background: An estimate of 90% effective dose (ED90) of oxytocin infusion has already been proved effective in non-laboring parturients. However, the requirements of oxytocin for elderly parturients with prior history of cesarean delivery (CD) may be higher. The aim of this study was to find the optimum oxytocin infusion rate for preventing uterine atony during CD in elderly parturients with prior history of CD.Method: We performed a randomized, double-blinded study in 120 healthy elderly parturients with prior history of CD scheduled for elective CD under combined spinal–epidural (CSE) anesthesia. Participants were treated with oxytocin infusion randomly at the rates of 0, 4, 8, 12, 16, or 20 IU h−1 after the delivery of infants. Following oxytocin administration, a blinded obstetrician evaluated the uterine tone (UT), verbally describing it using numerical scales (0–10: 0, no UT; 10, optimal UT) as either adequate or inadequate at the time intervals of 3, 6, and 9 min. Maternal adverse effects, requirements for additional uterotonic agents, delivery–placenta delivery time (PD), and estimated blood loss (EBL) were recorded.Results: The 50% effective dose (ED50) and 90% effective dose (ED90) of oxytocin infusion were 14.6 IU h−1 (95% confidence interval 12.0–18.4 IU h−1) and 27.7 IU h−1 (95% confidence interval 22.5–39.4 IU h−1), respectively. As the rate of infusion was increased in parturients, the rescue oxytocin dose and delivery-PD time were decreased. Parturients who received 0 IU h−1 oxytocin at 3, 6, and 9 min obtained lower UT scores than those who received 16 and 20 IU h−1 oxytocin (p &lt; 0.05, respectively). No significant differences were observed among groups in EBL and maternal adverse effects.Conclusion: The infusion rate of oxytocin at 14.57 and 27.74 IU h−1 produces adequate UT in 50% and 90% of elderly parturients with prior history of CD, respectively. An oxytocin infusion rate of 27.7 IU h−1 is suggested to be the optimal dose for preventing uterine atony during CD in elderly parturients with prior history of cesarean delivery.Clinical Trial Registration: [https://www.chictr.org.cn/bin/project/edit?pid=62489], Identifier: [ChiCTR2000038891].
Effect of physical activity on attention in school-age children with ADHD: a systematic review and meta-analysis of randomized controlled trials
Authors: Li Dong , Li Lan , Zang Wanli , Wang Deng , Miao Chuyuan , Li Chenmu , Zhou Li , Yan Jin 
Published: July 2023

Background: Attention problems are one of the core symptoms of Attention-deficit/hyperactivity disorder (ADHD) in children. Previous studies have shown that physical activity intervention has a positive impact on executive function in children and adolescents with ADHD, but there is limited research on attention problems in school-aged children with ADHD. There are still uncertainties about the appropriate physical activity interventions to improve attention problems in this population. This study conducted a Meta-analysis of randomized controlled trials (RCTs) related to physical activity intervention for attention problems in school-aged children with ADHD, providing a certain reference for precise intervention in attention problems for this population.Methods: We systematically searched the following databases up to October 2022: PubMed, Embase, Web of Science, and Cochrane Library, to identify RCTs that investigated the effects of physical activity interventions on children with ADHD. Two investigators independently conducted literature screening, extraction, and quality assessment. We performed a meta-analysis using Stata 15.1.Results: In total, we included 10 studies in this meta-analysis. The results indicated that physical activity intervention had a moderate effect in improving attention problems in school-aged children with ADHD (SMD = −0.48, 95% CI: 0.85, −0.07, p &lt; 0.05). Furthermore, subgroup analysis showed that the effect of physical activity intervention was moderated by intervention type, frequency, and period, rather than the physical activity environment or single intervention time.Conclusion: Our study suggests that cognitively engaging exercise is more effective in improving attention problems in school-aged children with ADHD. Specifically, when cognitive-engaging exercise is used as the type of physical activity and the intervention frequency is less than 3 times per week, with an intervention period of less than weeks, it is most beneficial for improving attention problems in school-aged children with ADHD. However, we should also consider individual differences in children with respect to their ADHD symptoms and accurately evaluate each child’s specific symptoms before intervention.Systematic Review Registration: identifier (CRD42022363255).
Testing the somatic marker hypothesis in decisions-from-experience with non-stationary outcome probabilities
Authors: Wright Rebecca J. , Rakow Tim 
Published: July 2023

IntroductionThe Somatic Marker Hypothesis (SMH) posits that in experience-based choice, people develop physiological reactions that mark options as either positive or negative. These somatic markers aid decision making because they differentiate between “good” and “bad” options during pre-choice deliberation.MethodsWe examined this proposed role for somatic states in two decision-from-experience tasks (each N = 36) in which participants selected repeatedly with full feedback (i.e., for obtained and forgone outcomes) between two unlabeled options that returned wins or losses, with half receiving an additional summary of past outcomes. The probabilities of good and bad outcomes changed at an unannounced point. Participants completed a 100-trial game with a switch in the optimal option after trial 40 (Study 1) or a 200-trial game with switch points after trial 40 and trial 120 (Study 2). Skin conductance (SC) was measured continuously as an index of emotional intensity, from which we extracted measures of anticipatory SC (pre-choice) and outcome SC (post-choice).ResultsParticipants reliably selected the optimal option prior to any switches. They also altered their choices appropriately when the payoffs changed, though optimal play following payoff switches was reduced. Losses resulted in a greater outcome SC than wins, but only in Study 1, as did the finding that the outcome SC was greater when the forgone outcome was positive. Anticipatory SC did not reliably predict optimal play in either study.DiscussionThese results provide little support for the SMH. Our studies point to the importance of using diverse tasks and measures and very large sample sizes when testing the role of somatic states in decision making.