bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and Risk Factors of Postpartum Hemorrhage in China: A Multicenter Retrospective Study
Authors: Li Sijian , Gao Jinsong , Liu Juntao , Hu Jing , Chen Xiaoxu , He Jing , Tang Yabing , Liu Xinghui , Cao Yinli , Liu Xiaowei , Wang Xietong 
Published: August 2021

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide but the incidence and its risk factors in China is limited. The objective of this study is to investigate the incidence and the risk factors of PPH in Chinese women.Methods: A multi-center retrospective study of pregnant women at ≥28 weeks of gestation was conducted. Logistic regression was used to identify potential risk factors of PPH and receiver operating characteristic curve was used to evaluate the predictive performance of the identified risk factors. Subgroup analysis focusing on the number of fetus and the mode of delivery was conducted.Results: A total of 99,253 pregnant women were enrolled and 804 (0.81%) experienced PPH. The subgroup analysis revealed that the incidence of PPH was 0.75, 2.65, 1.40, and 0.31% in singletons, twin pregnancies, cesarean sections, and vaginal deliveries, respectively. Placenta previa and placenta accreta were the predominant risk factors of PPH in the overall population and all subgroups. A twin pregnancy was a risk factor for PPH regardless of the mode of delivery. Obesity, and multiparity were risk factors for PPH in both singletons and cesarean section cases, but the latter predicted a reduced probability of PPH in vaginal deliveries. Macrosomia was associated with increased risk of PPH in singletons or vaginal deliveries. In women who delivered vaginally, preeclampsia was associated with a higher risk of PPH. The areas under the curve for the overall cohort, singletons, twin pregnancies, cesarean section cases, and vaginal deliveries were 0.832 (95% confidence interval [CI] 0.813–0.851), 0.824 (95% CI 0.803–0.845), 0.686 (95% CI 0.617–0.755), 0.854 (95% CI 0.834–0.874), and 0.690 (95% CI 0.646–0.735), respectively.Conclusions: The risk factors of PPH varied slightly based on the number of fetuses and the mode of delivery, while placenta previa and placenta accreta were the two major risk factors. A combination of the identified risk factors yielded a satisfactory predictive performance in determining PPH in the overall cohort, singletons pregnancies, and women who delivered by cesarean section, whereas the performance was moderate in twin pregnancies and in women delivering vaginally.
Efficacy of a Novel Exoskeletal Robot for Locomotor Rehabilitation in Stroke Patients: A Multi-center, Non-inferiority, Randomized Controlled Trial
Authors: Li Yongqiang , Fan Tao , Qi Qi , Wang Jun , Qiu Huaide , Zhang Lingye , Wu Xixi , Ye Jing , Chen Gong , Long Jianjun , Wang Yulong , Huang Guozhi , Li Jianan 
Published: August 2021

Objective: To investigate the efficacy and safety of a novel lower-limb exoskeletal robot, BEAR-H1 (Shenzhen Milebot Robot Technology), in the locomotor function of subacute stroke patients.Methods: The present study was approved by the ethical committee of the First Affiliated Hospital of Nanjing Medical University (No. 2019-MD-43), and registration was recorded on the Chinese Clinical Trial Registry with a unique identifier: ChiCTR2100044475. A total of 130 patients within 6 months of stroke were randomly divided into two groups: the robot group and the control group. The control group received routine training for walking, while in the robot group, BEAR-H1 lower-limb exoskeletal robot was used for locomotor training. Both groups received two sessions daily, 5 days a week for 4 weeks consecutively. Each session lasted 30 min. Before treatment, after treatment for 2 weeks, and 4 weeks, the patients were assessed based on the 6-minute walking test (6MWT), functional ambulation scale (FAC), Fugl-Meyer assessment lower-limb subscale (FMA-LE), and Vicon gait analysis.Results: After a 4-week intervention, the results of 6MWT, FMA-LE, FAC, cadence, and gait cycle in the two groups significantly improved (P &lt; 0.05), but there was no significant difference between the two groups (P &gt; 0.05). The ratio of stance phase to that of swing phase, swing phase symmetry ratio (SPSR), and step length symmetry ratio (SLSR) was not significantly improved after 4 weeks of training in both the groups. Further analyses revealed that the robot group exhibited potential benefits, as the point estimates of 6MWT and Δ6MWT (post-pre) at 4 weeks were higher than those in the control group. Additionally, within-group comparison showed that patients in the robot group had a significant improvement in 6MWT earlier than their counterparts in the control group.Conclusions: The rehabilitation robot in this study could improve the locomotor function of stroke patients; however, its effect was no better than conventional locomotor training.
Sex Differences in the Blood Oxygen Level-Dependent Signal to Placebo Analgesia and Nocebo Hyperalgesia in Experimental Pain: A Functional MRI Study
Authors: Shi Yu , Zhan Hongrui , Zeng Yanyan , Huang Shimin , Cai Guiyuan , Yang Jianming , Wu Wen 
Published: August 2021

ObjectivePlacebo as well as nocebo responses are widely found in scientific research and clinical practice. Growing evidence suggests sex differences in placebo as well as nocebo responses. However, data concerning this question are still insufficient. This study examined whether the BOLD signals of two responses, as measured with functional MRI (fMRI), differ by sex under conditions of equivalent experimental pain perception.MethodThirty-one healthy volunteers (14 female) underwent two fMRI scans, once during a placebo intervention and once during a nocebo intervention, pseudorandomly ordered, in an acute lower back pain (ALBP) model. We collected visual analog scale (VAS) data after each scanning. fMRI data from different sex groups were subjected to functional connectivity (FC) analysis and behavioral correlation analysis (BCA).ResultsThe results showed statistical differences in VAS scores between male and female participants, in both placebo and nocebo responses. Both groups also showed reduced FC in the pain-associated network of the placebo response and elevated FC in the pain-related network of the nocebo response. However, in the placebo condition, male participants displayed increased FC in the ventromedial prefrontal cortex, parahippocampal gyrus (PHP), and posterior cingulate cortex (PCC), while female participants showed increased FC in the dorsolateral prefrontal cortex, hippocampal gyrus (HP), and insular cortex (IC). In the nocebo condition, male participants showed decreased FC in the PCC and HP, while female participants displayed decreased FC in the mid-cingulate cortex, thalamus (THS), and HP. The BCA results of the two groups were also different.ConclusionWe found that the endogenous opioid system and reward circuit play a key role in sex differences of placebo response and that anxiety and its secondary reactions may cause the sex differences of nocebo response.
Effects of Prior Antiplatelet Therapy on Mortality, Functional Outcome, and Hematoma Expansion in Intracerebral Hemorrhage: An Updated Systematic Review and Meta-Analysis of Cohort Studies
Authors: Wu Yujie , Zhang Donghang , Chen Hongyang , Liu Bin , Zhou Cheng 
Published: August 2021

Background and Objective: Antiplatelet therapy (APT) is widely used and believed to be associated with increased poor prognosis by promoting bleeding in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to determine whether prior APT is associated with mortality, functional outcome, and hematoma expansion in ICH patients.Methods: The PubMed, Embase, and Web of Science databases were searched for relevant published studies up to December 11, 2020. Univariate and multivariable adjusted odds ratios (ORs) were pooled using a random effects model. Cochran's chi-squared test (Cochran's Q), the I2 statistic, and meta-regression analysis were used to evaluate the heterogeneity. Meta-regression models were developed to explore sources of heterogeneity. Funnel plots were used to detect publication bias. A trim-and-fill method was performed to identify possible asymmetry and assess the robustness of the conclusions.Results: Thirty-one studies fulfilled the inclusion criteria and exhibited a moderate risk of bias. Prior APT users with intracerebral hemorrhage (ICH) had a slightly increased mortality in both univariate analyses [odds ratio (OR) 1.39, 95% CI 1.24–1.56] and multivariable adjusted analyses (OR 1.41, 95% CI 1.21–1.64). The meta-regression indicated that for each additional day of assessment time, the adjusted OR for the mortality of APT patients decreased by 0.0089 (95% CI: −0.0164 to −0.0015; P = 0.0192) compared to that of non-APT patients. However, prior APT had no effects on poor function outcome (pooled univariate OR: 0.99, 95% CI 0.59–1.66; pooled multivariable adjusted OR: 0.93, 95% CI 0.87–1.07) or hematoma growth (pooled univariate OR: 1.23, 95% CI 0.40–3.74, pooled multivariable adjusted OR: 0.94, 95% CI 0.24–3.60).Conclusions: Prior APT was not associated with hematoma expansion or functional outcomes, but there was modestly increased mortality in prior APT patients. Higher mortality of prior APT patients was related to the strong influence of prior APT use on early mortality.Systematic Review Registration:PROSPERO Identifier [CRD42020215243].
Long-Term Efficacy Outcomes of Natalizumab vs. Fingolimod in Patients With Highly Active Relapsing-Remitting Multiple Sclerosis: Real-World Data From a Multiple Sclerosis Reference Center
Authors: Boziki Marina , Bakirtzis Christos , Giantzi Virginia , Sintila Styliani-Aggeliki , Kallivoulos Stylianos , Afrantou Theodora , Nikolaidis Ioannis , Ioannidis Panagiotis , Karapanayiotides Theodoros , Koutroulou Ioanna , Parissis Dimitrios , Grigoriadis Nikolaos 
Published: August 2021

Background: Natalizumab (NTZ) and fingolimod (FTY) are second-line disease modifying treatments (DMTs) approved for Relapsing – Remitting Multiple Sclerosis (RRMS). Few studies are available on a direct comparison between NTZ and FTY, based on post-marketing experience, with conflicting results and reporting relatively short follow-up period.Aim: We hereby report real-world experience of a MS Center with respect to NTZ vs. FTY comparison in terms of efficacy and safety, referencing long-term follow-up.Methods: We used retrospective data for all patients that received 2nd-line treatment NTZ (since May 2007) or FTY (since September 2011). Primary endpoints were, among others, annual EDSS score (mean change from baseline), time to disability worsening or improvement, Annualized Relapse Rate (ARR) after 12 and 24 months and upon total treatment duration, time to first relapse and time to radiological progression.Results: A total of 138 unmatched patients, 84 treated with NTZ and 54 treated with FTY were included. Following Propensity Score (PS) matching, 31 patients in each group were retained. Mean follow-up period for NTZ- and FTY-treated patients was 4.43 ± 0.29 and 3.59 ± 0.32 years (p = 0.057), respectively. In the matched analysis, time to disability improvement and time to disability worsening was comparable between groups. A higher proportion of patients remained free of relapse under NTZ, compared to FTY (Log Rank test p = 0.021, HR: 0.25, 95% CI: 0.08–0.8), as well as free of MRI activity (Log Rank test p = 0.006, HR: 0.26, 95% CI: 0.08–0.6). Treatment discontinuation due to MRI activity was significantly higher for FTY-treated patients compared to NTZ (Log Rank test p = 0.019, HR: 0.12, 95% CI: 0.05–0.76).Conclusion: Our results indicate toward NTZ superiority with respect to relapse and MRI activity outcomes. The fact that NTZ-treated patients may achieve long-standing clinical and radiological remission points toward the need for long follow-up data.
Beneficial Effect of Immune-Enhanced Enteral Nutrition on Immune Function in Patients With Severe Neurological Diseases: A Single-Center Randomized Controlled Trial
Authors: Chao Ke , Wang Dong , Yang Hongfu , Ma Ning , Liu Qilong , Sun Xiaoge , Sun Rongqing 
Published: August 2021

Background: Undernutrition is the main reason for the use of artificial nutrition in patients with severe neurological diseases. However, the clinical and immunological outcomes of enteral nutrition supplemented with immunomodulatory nutrients in these patients remain unclear.Methods: In this single-center, randomized controlled study, 57 patients with severe neurological diseases were randomly divided into the following two groups according to the type of enteral nutrition they would receive: immune-enhancing (IE) (n = 27) and non-IE (NIE) (n = 30). The IE and NIE groups received enteral nutrition supplemented with immunomodulatory nutrients and standard enteral nutrition, respectively. We compared the nutritional status and the state of cellular immunity between the patients of the two groups. Clinical and immunological variables were evaluated following nutritional treatment.Results: Feeding intolerance was lower in the IE than that in the NIE group (P = 0.04). However, there were no significant differences between the results of the two groups in terms of length of stay in the intensive care unit or hospital, extubation time, or body mass index (P &gt; 0.05). The CD4+ T-lymphocyte count and CD4+/CD8+ ratio in the peripheral blood increased significantly in the IE group. The expression of CD28 activated cell surface markers was higher in the IE than in the NIE group. In addition, increased plasma interferon-γ levels were recorded in the IE group, whereas the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-10 decreased.Conclusions: Immune-enhanced enteral nutrition could improve the immune status and feeding tolerance in patients with severe neurological diseases.Trial Registration:www.chictr.org.cn/index.aspx, identifier: ChiCTR-IPR-17013909.
Changes in Intestinal Flora Structure and Metabolites Are Associated With Myocardial Fibrosis in Patients With Persistent Atrial Fibrillation
Authors: Liu Langsha , Su Juan , Li Rui , Luo Fanyan 
Published: August 2021

Background: The occurrence of atrial fibrillation is often accompanied by myocardial fibrosis. An increasing number of studies have shown that intestinal flora is involved in the occurrence and development of a variety of cardiovascular diseases. This study explores the relationship between changes in the structure and function of intestinal flora and the progression of myocardial fibrosis in patients with persistent atrial fibrillation.Methods: Serum and stool samples were collected from 10 healthy people and 10 patients with persistent atrial fibrillation (PeAF), and statistical analyses were performed on the subjects' clinical baseline conditions. ELISA was used to measure the levels of carboxy-terminal telopeptide of type I collagen (CTX-I), propeptide of type I procollagen (PICP), procollagen III N-terminal propeptide (PIIINP), fibroblast growth factor-23 (FGF-23), and transforming growth factor-beta 1 (TGF-β1) in serum. Through 16S rRNA sequencing technology, the structural composition of the intestinal flora was detected and analyzed. In addition, metabolomics data were analyzed to determine the differences in the metabolites produced by the intestinal flora of the subjects.Results: By comparing the baseline data of the subjects, it was found that compared with those of the control group, the levels of creatinine (CRE) and serum uric acid (SUA) in the serum of PeAF patients were significantly increased. In addition, we found that the levels of CTX-I, PICP, PIIINP, and TGF-β1 in the serum of PeAF patients were significantly higher than those of the control group subjects. Although the control and PeAF groups exhibited no significant differences in the α diversity index, there were significant differences in the β diversity indexes (Bray-Curtis, weighted UniFrac and Anosim). At the phylum, family and species levels, the community structure and composition of the intestinal flora of the control group and those of the PeAF group showed significant differences. In addition, the compositions of the intestinal metabolites in the two different groups of people were significantly different. They were correlated considerably with PIIINP and specific communities in the intestinal flora.Conclusion: Pathologically, PeAF patients may have a higher risk of myocardial fibrosis. Systematically, abnormal changes in the structure and composition of the intestinal flora in PeAF patients may lead to differences in intestinal metabolites, which are involved in the process of myocardial fibrosis through metabolite pathways.
Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Zhao Wenhua , Jiang Wei , Wang Huilin , He Jianbo , Su Cuiyun , Yu Qitao 
Published: August 2021

ObjectivesTo evaluate the impact of smoking history on the clinical benefit of immunotherapy in patients with non-small cell lung cancer (NSCLC).MethodsTwenty-three randomized clinical trials and seven real-world studies were included in this meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) and odds ratios for the overall response rate (ORR) were extracted. A fixed-effects or random-effects model was applied to obtain pooled estimates.ResultsData from 16 high-quality trials involving 10,643 NSCLC patients receiving either immunotherapy or chemotherapy/placebo enabled direct comparison of the survival impact of smoking. Anti-PD-1/PD-L1/CTLA-4 immunotherapy was found to significantly prolong OS and PFS as compared to chemotherapy/placebo in smokers (HR for OS, 0.76 [0.69–0.83], P&lt;0.00001; HR for PFS, 0.65 [0.56–0.75], P&lt;0.00001), and these trends were less or not significant in non-smokers (HR for OS, 0.91 [0.78–1.06], P=0.25; HR for PFS, 0.68 [0.45–1.03], P=0.07). Consistent results were obtained for the first-line or second/third-line use of immunotherapy and for non-squamous NSCLC patients only. Furthermore, the data from 7 trials and 7 real-world studies involving 4,777 patients receiving immunotherapy allowed direct comparison of therapeutic outcomes between smokers and non-smokers. Prolonged OS (HR 0.86 [0.75–0.99], P=0.04) and PFS (HR 0.69 [0.60–0.81], P&lt;0.0001) and a higher response rate (ORR 1.20 [0.94–1.53], P=0.15) were observed in smokers compared to non-smokers receiving immunotherapy.ConclusionsImmunotherapy was found to have a greater benefit in NSCLC patients with a smoking history than in those who had never smoked.
Second Primary Malignancies in Patients With Hepatocellular Carcinoma: A Population-Based Analysis
Authors: Kong Junjie , Yu Guangsheng , Si Wei , Li Guangbing , Chai Jiawei , Liu Yong , Liu Jun 
Published: August 2021

BackgroundSecond primary malignancy (SPM) is becoming a threat for the health of cancer survivors. However, data on the features and results of patients with hepatocellular carcinoma (HCC) with SPMs are scarce. This study aimed to explore the characteristics of HCC patients with SPMs and to screen HCC patients who are at a high risk of developing SPMs.MethodHCC patients diagnosed between 2000 and 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Eligible patients were divided into the only one primary malignancy and SPM groups. The Fine-Gray proportional subdistribution hazards model was used to explore the risk factors of developing SPMs, and a competing-risk model was established to predict the probability of developing SPMs for HCC patients after initial diagnosis. The calibration curves, concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.ResultsA total of 40,314 HCC patients were identified, 1,593 (3.95%) of whom developed SPMs 2 months after the initial diagnosis with a maximum follow-up time of approximately 18 years. The 3-, 5-, and 10-year cumulative incidence of SPMs were 2.35%, 3.12%, and 4.51%, respectively. Age at initial diagnosis, extent of disease, tumor size, and treatment were identified as the independent risk factors of developing SPMs and integrated into the competing-risk nomogram. The C-index of the nomogram was 0.677 (95% confidence interval 0.676–0.678), and the calibration curves showed an excellent agreement between the nomogram prediction and the actual observations. Furthermore, DCA indicated that the nomogram had good net benefits in clinical scenarios.ConclusionsHCC survivors remain at a high risk of developing SPMs. The development of SPMs was associated with the clinical features and treatment strategies. A competing-risk nomogram was constructed to help surgeons identify the patients who are at a high risk of developing SPMs and contribute to the further management of SPMs.
Evolution of Intestinal Microbiota of Asphyxiated Neonates Within 1 Week and Its Relationship With Neural Development at 6 Months
Authors: Zhang Xiaojiao , Liu Lili , Bai Wei , Han Ying , Hou Xinlin 
Published: August 2021

Introduction: Asphyxia is an emergent condition in neonates that may influence the function of the nervous system. Research has shown that intestinal microbiota is very important for neurodevelopment. Studies regarding the association between gut microbiota and neurodevelopment outcome in asphyxiated newborns remain scarce.Objective: To study the microbial characteristics of asphyxiated neonates within 1 week of life and to investigate their relationship with neural development at 6 months.Methods: The feces produced on days 1, 3, and 5, and the clinical data of full-term neonates with asphyxia and without asphyxia, delivered from March 2019 to October 2020 at Peking University First Hospital, were collected. We used 16S ribosomal deoxyribonucleic acid amplicon sequencing to detect the intestinal microbiota of asphyxiated neonates and neonates in the control group. We followed up asphyxiated neonates for 6 months and used the Ages and Stages Questionnaires-3 (ASQ-3) to evaluate their development.Results: A total of 45 neonates were enrolled in the study group and 32 were enrolled in the control group. On day 1, the diversity and richness of the microflora of the study group were more than those of the control group. Non-metric multidimensional scaling analysis showed significant differences in the microbiota of the two groups on days 1, 3, and 5. At the phylum level, the main microflora of the two groups were not different. At the genus level, the study group had increased relative abundance of Clostridium_sensu_stricto_1, Lachnoclostridium, Fusicatenibacter, etc. on day 1. On day 3, the relative abundance of Clostridium_sensu_stricto_1, Fusicatenibacter, etc. was still greater than that of the control group, and the relative abundance of Staphylococcus was less than that of the control group. On day 5, the relative abundance of Clostridium_sensu_stricto_1 and Lachnoclostridium was still higher than that of the control group, and the relative abundance of Dubosiella in the study group was significantly increased. At the species level, on day 3, the relative abundance of Staphylococcus caprae in the study group was less than that in the control group. Linear discriminant analysis effect size showed that the microbiota of the study group mainly consisted of Lachnospiraceae and Clostridia on day 1 and Clostridia on day 3. In the control group, Staphylococcus was the dominant bacterium on day 3. Neonates in the study group were followed up for 6 months, and the communication score of ASQ-3 was negatively correlated with the relative abundance of Lachnospiraceae and Clostridia on day 1.Conclusion: The diversity and richness of the microbiota of asphyxiated neonates on the first day of life were significantly increased and mainly consisted of pathogenic flora. Lachnospiraceae and Clostridia found in neonates with asphyxia on day 1 of life may be related to neural development at 6 months.