bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Tenofovir Alafenamide Fumarate in Early-Middle Pregnancy for Mothers With Chronic Hepatitis B
Authors: Chen Ruochan , Zou Ju , Long Liyuan , Huang Haiyue , Zhang Min , Fan Xuegong , Huang Yan 
Published: January 2022

BackgroundTenofovir alafenamide fumarate has been used in late pregnancy; however, no data exist regarding its safety and effectiveness in early and middle pregnancy for mothers with hepatitis B virus infection.AimsTo design a prospective study to investigate the efficacy and safety of TAF in pregnant women with chronic HBV infection during early-middle pregnancy.MethodsPregnant women with active chronic hepatitis B who received tenofovir alafenamide fumarate during early and middle pregnancy were enrolled and followed up until 6 months postpartum. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoints were maternal hepatitis B virus DNA reduction at delivery and mother-to-child transmission rate.ResultsAmong 98 mothers enrolled, 31 initiated tenofovir alafenamide fumarate in early pregnancy, and 57 in middle pregnancy. The mean (± standard deviation) age was 29.00 (±3.81) years. At delivery, 100% (98/98) of the mothers achieved hepatitis B virus DNA levels &lt;200,000 IU/L. Ninety-eight infants were born, and none had congenital defects or malformations. All infants received hepatitis B virus immunoprophylaxis. The mother-to-child transmission rate was 0%. Growth parameters including body weight, height, and head circumference were comparable to the national standards for physical development. No severe adverse effects were reported in either mothers or infants. No severe liver function damage occurred in any of the mothers.ConclusionsInitiating tenofovir alafenamide fumarate in early and middle pregnancy appears safe for both mothers and infants, and it is effective for controlling maternal disease as well as interrupting mother-to-child transmission.
Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents
Authors: Hassan Entesar A. , Shehadi Ihsan A. , Elmaghraby Awatef M. , Mostafa Hadir M. , Zayed Salem E. , Abdelmonsef Aboubakr H. 
Published: January 2022

In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one(1)and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione(2)was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol(3, 4), 3,4-dihydroquinoline(7, 8)and thiopyran(10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9)was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities againstCandida albicansandAspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid(9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.
Atrial Fibrillation Is Not an Independent Determinant of Mortality Among Critically Ill Acute Ischemic Stroke Patients: A Propensity Score-Matched Analysis From the MIMIC-IV Database
Authors: Wu Chen-Shu , Chen Po-Huang , Chang Shu-Hao , Lee Cho-Hao , Yang Li-Yu , Chen Yen-Chung , Jhou Hong-Jie 
Published: January 2022

Background/ObjectiveThis study was conducted to investigate the clinical characteristics and outcomes of patients with acute ischemic stroke and atrial fibrillation (AF) in intensive care units (ICUs).MethodsIn the Medical Information Mart for Intensive Care IV database, 1,662 patients with acute ischemic stroke were identified from 2008 to 2019. Of the 1,662 patients, 653 had AF. The clinical characteristics and outcomes of patients with and without AF were compared using propensity score matching (PSM). Furthermore, univariate and multivariate Cox regression analyzes were performed.ResultsOf the 1,662 patients, 39.2% had AF. The prevalence of AF in these patients increased in a stepwise manner with advanced age. Patients with AF were older and had higher Charlson Comorbidity Index, CHA2DS2-VASc Score, HAS-BLED score, and Acute Physiology Score III than those without AF. After PSM, 1,152 patients remained, comprising 576 matched pairs in both groups. In multivariate analysis, AF was not associated with higher ICU mortality [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.64–1.42] or in-hospital mortality (HR, 1.08; 95% CI, 0.79–1.47). In Kaplan–Meier analysis, no difference in ICU or in-hospital mortality was observed between patients with and without AF.ConclusionsAF could be associated with poor clinical characteristics and outcomes; however, it does not remain an independent short-term predictor of ICU and in-hospital mortality among patients with acute ischemic stroke after PSM with multivariate analysis.
Mast Syndrome Outside the Amish Community: SPG21 in Europe
Authors: Amprosi Matthias , Indelicato Elisabetta , Nachbauer Wolfgang , Hussl Anna , Stendel Claudia , Eigentler Andreas , Gallenmüller Constanze , Boesch Sylvia , Klopstock Thomas 
Published: January 2022

Background:Mast syndrome is a rare disorder belonging to the group of hereditary spastic paraplegias (HSPs). It is caused by bi-allelic mutations in the ACP33 gene, and is originally described in Old Order Amish. Outside this population, only one Japanese and one Italian family have been reported. Herein, we describe five subjects from the first three SPG21 families of German and Austrian descent.Methods:Five subjects with complicated HSP were referred to our centers. The workup consisted of neurological examination, neurophysiological and neuropsychological assessments, MRI, and genetic testing.Results:Onset varied from child- to adulthood. All patients exhibited predominant spastic para- or tetraparesis with positive pyramidal signs, pronounced cognitive impairment, ataxia, and extrapyramidal signs. Neurophysiological workup showed abnormal motor and sensory evoked potentials in all the patients. Sensorimotor axonal neuropathy was present in one patient. Imaging exhibited thin corpus callosum and global brain atrophy. Genetic testing revealed one heterozygous compound and two homozygous mutations in the ACP33 gene.Conclusion:Herein, we report the first three Austrian and two German patients with SPG21, presenting a detailed description of their clinical phenotype and disease course. Our report adds to the knowledge of this extremely rare disorder, and highlights that SPG21 must also be considered in the differential diagnosis of complicated HSP outside the Amish community.
Epilepsy With Suicide: A Bibliometrics Study and Visualization Analysis via CiteSpace
Authors: Guo Yi , Xu Zheng-Yan-Ran , Cai Meng-Ting , Gong Wen-Xin , Shen Chun-Hong 
Published: January 2022

Objective:The purpose of this study was to analyze the research status of epilepsy with suicide and to determine the hotspots and frontiers via CiteSpace.Method:We searched the Web of Science Core Collection (WoSCC) for studies related to epilepsy and suicide from inception to September 30, 2021. We used CiteSpace to generate online maps of collaboration between countries, institutions, and authors, and revealed hot spots and frontiers in epilepsy with suicide.Results:A total of 631 publications related to epilepsy with suicide were retrieved from the WoSCC. Andres M. Kanner was the most published author (25 papers). The USA and Columbia University were the leading country and institution in this field, with 275 and 25 papers, respectively. There were active cooperation between institutions, countries, and authors. Hot topics focused on depression, antiseizure medications, pediatric epilepsy, and risk factors of suicide in patients with epilepsy (PWEs).Conclusions:Based on the CiteSpace findings, this study detected active collaboration among countries, institutions and authors. The main current research trends include suicide caused by depression, suicide caused by the use of antiseizure medications, suicide in children with epilepsy, and risk factors for suicide in PWEs. Thus, more attention should be paid to the psychiatric comorbidity of PWEs (especially pediatric epilepsy), the suicidal tendency of PWEs, and the rational use of antiseizure medications in the future.
Aerobic Exercise Training-Induced Changes on DNA Methylation in Mild Cognitively Impaired Elderly African Americans: Gene, Exercise, and Memory Study - GEMS-I
Authors: Ngwa Julius S. , Nwulia Evaristus , Ntekim Oyonumo , Bedada Fikru B. , Kwabi-Addo Bernard , Nadarajah Sheeba , Johnson Steven , Southerland William M. , Kwagyan John , Obisesan Thomas O. 
Published: January 2022

BackgroundDNA methylation at CpG sites is a vital epigenetic modification of the human genome affecting gene expression, and potentially, health outcomes. However, evidence is just budding on the effects of aerobic exercise-induced adaptation on DNA methylation in older mild cognitively impaired (MCI) elderly African American (AAs). Therefore, we examined the effects of a 6-month aerobic exercise-intervention on genome-wide DNA methylation in elderly AA MCI volunteers.DesignElderly AA volunteers confirmed MCI assigned into a 6-month program of aerobic exercise (eleven participants) underwent a 40-min supervised-training 3-times/week and controls (eight participants) performed stretch training. Participants had maximal oxygen consumption (VO2max) test and Genome-wide methylation levels at CpG sites using the Infinium HumanMethylation450 BeadChip assay at baseline and after a 6-month exercise program. We computed false discovery rates (FDR) using Sidak to account for multiplicity of tests and performed quantitative real-time polymerase chain-reaction (qRT-PCR) to confirm the effects of DNA methylations on expression levels of the top 5 genes among the aerobic participants. CpG sites identified from aerobic-exercise participants were similarly analyzed by the stretch group to quantify the effects of exercise-induced methylation changes among the group of stretch participants.ResultsEleven MCI participants (aerobic: 73% females; mean age 72.3 ± 6.6 years) and eight MCI participants (stretch: 75% female; mean age 70.6 ± 6.7 years) completed the training. Aerobic exercise-training was associated with increases in VO2max and with global hypo- and hypermethylation changes. The most notable finding was CpG hypomethylation within the body of the VPS52 gene (P = 5.4 × 10–26), a Golgi-associated protein, involved in intracellular protein trafficking including amyloid precursor protein. qRT-PCR confirmed a nearly twofold increased expression of VPS52. Other top findings with FDR q-value &lt; 10–5, include hypomethylations of SCARB1 (8.8 × 10–25), ARTN (6.1 × 10–25), NR1H2 (2.1 × 10–18) and PPP2R5D (9.8 × 10–18).ConclusionWe conclude that genome-wide DNA methylation patterns is associated with exercise training-induced methylation changes. Identification of methylation changes around genes previously shown to interact with amyloid biology, intracellular protein trafficking, and lipoprotein regulations provide further support to the likely protective effect of exercise in MCI. Future studies in larger samples are needed to confirm our findings.
Different Doses of Calcium Supplementation to Prevent Gestational Hypertension and Pre-Eclampsia: A Systematic Review and Network Meta-Analysis
Authors: Chen Dexin , Wang Hong , Xin Xing , Zhang Long , Yu Aihong , Li Shuwen , He Rongxia 
Published: January 2022

ObjectiveCalcium supplementation can prevent gestational hypertension and pre-eclampsia. However, besides the non-consensus of existing studies, there is a lack of evidence regarding the optimal dosing of calcium.MethodEight electronic databases, namely, the Cochrane Library, PUBMED, Web of Science, EMBASE, WANGFANG, VIP, CBM, and CNKI, were searched. The studies were retrieved from inception to July 13, 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria. In particular, the calcium supplementation doses were divided into three groups, namely, the high-dose (≥1.5 g), medium-dose (1.0–1.49 g), and the low-dose group (&lt;1.0 g). The participants were also divided into high-risk and low-risk groups, according to the risk of developing gestational hypertension and pre-eclampsia.Results and DiscussionA total of 48 studies were incorporated into the final analyses. All doses of calcium supplementation reduced the incidence of gestational hypertension in the low-risk population (low dose - three studies; medium dose- 11 studies; high dose- 28 studies), whereas the medium-dose (three studies) reduced the incidence of gestational hypertension in high-risk groups. Moreover, a medium dose of calcium supplementation had the maximum effect in reducing gestational hypertension in low-risk and high-risk populations. The medium (three studies) and high doses (13 studies) of calcium supplementation reduced the incidence of pre-eclampsia in the low-risk groups. However, a medium-dose calcium supplementation maximally prevented pre-eclampsia in the low-risk population. The authenticity and reliability of the results were reduced due to the limitations of contemporary studies in terms of experimental design, result measurement, statistics, and evidence quality. Therefore, high-quality studies with larger sample size are required to evaluate further the effect of calcium supplementation in preventing gestational hypertension and pre-eclampsia.
Lipid Changes During Endocrine Therapy in Breast Cancer Patients: The Results of a 5-Year Real-World Retrospective Analysis
Authors: He Tao , Li Xu , Li Jiayuan , Wang Zhu , Fan Yuan , Li Xiusong , Fu Zhoukai , Wu Yunhao , Lv Qing , Luo Ting , Zhong Xiaorong , Chen Jie 
Published: January 2022

BackgroundThe aim of this study was to investigate the status of serum lipids during endocrine therapy.MethodsWe retrospectively analysed lipid profiles during the 5-year treatment of 1487 consecutive postoperative BC patients. Lipid parameters included triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C). Those biomarkers were measured at baseline and 1, 2, 3, 4 and 5 years following the initiation of endocrine therapy.ResultsFor premenopausal BC patients, LDL levels rapidly decreased at 1 year in the tamoxifen (TAM) group compared with baseline levels (p&lt;0.05), and this decline remained for the following 4 years. Additionally, LDL levels were significantly lower in the TAM group than in the nonendocrine group at all assessment time points (p&lt;0.05). Similarly, TC levels also decreased in the TAM group compared with baseline levels at all assessment time points (p&lt;0.05), and compared with the levels in the nonendocrine group, TC levels were also lower for the first 4 years. For postmenopausal BC patients, there was no significant difference in the lipid profiles (TG, TC, LDL and HDL) in the letrozole (LET), anastrozole (ANA) or exemestane (EXE) groups compared with the nonendocrine group. For patients who received TAM, compared with the nonendocrine group, TC levels decreased at 1 year, and LDL levels decreased at 1 and 2 years.ConclusionsTAM may improve LDL and TC levels in premenopausal BC patients. In postmenopausal BC patients, aromatase inhibitors (AIs) may have no adverse effects on lipid profiles, and TAM may have limited beneficial effects on serum lipids.
In Real Life, Low-Level HER2 Expression May Be Associated With Better Outcome in HER2-Negative Breast Cancer: A Study of the National Cancer Center, China
Authors: Li Yiqun , Abudureheiyimu Nilupai , Mo Hongnan , Guan Xiuwen , Lin Shaoyan , Wang Zijing , Chen Yimeng , Chen Shanshan , Li Qiao , Cai Ruigang , Wang Jiayu , Luo Yang , Fan Ying , Yuan Peng , Zhang Pin , Li Qing , Ma Fei , Xu Binghe 
Published: January 2022

BackgroundTo characterize the clinical and pathological features and survival of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer in China.MethodsThe China National Cancer Center database was used to identify 1,433 metastatic breast cancer patients with HER2-negative disease diagnosed between 2005 and 2015. Clinicopathological features, survival, and prognosis information were extracted. Overall survival (OS) was estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with OS were analyzed using Cox regression model with 95% confidence interval (95% CI).ResultsThere were 618 (43.1%) and 815 (56.9%) HER2-low and HER2-zero tumors out of 1,433 tumors, respectively. The proportion of hormone receptor (HR)-positive tumors was significantly higher in HER2-low tumors than in those with HER2-zero tumors (77.8% vs. 69.2%, p &lt; 0.001). Patients with HER2-low tumors survived significantly longer than those with HER2-zero tumors in the overall population (48.5 months vs. 43.0 months, p = 0.004) and HR-positive subgroup (54.9 months vs. 48.1 months, p = 0.011), but not in the HR-negative subgroup (29.5 months vs. 29.9 months, p = 0.718). Multivariate regression analysis revealed that HER2-low tumors were independently associated with increased OS in HER2-negative population (HR: 0.85, 95% CI: 0.73–0.98, p = 0.026).ConclusionOur findings demonstrate that HER2-low tumors could be identified as a more distinct clinical entity from HER2-zero tumors, especially for the HR-positive subgroup. A more complex molecular landscape of HER2-low breast cancer might exist, and more precise diagnostic algorithms for HER2 testing could be investigated, thus offering new therapeutic targets for breast cancer treatment.
Identification of Liver Immune Microenvironment-Related Hub Genes in Liver of Biliary Atresia
Authors: Zhang Jiaxu , Luo Yi , Feng Mingxuan , Xia Qiang 
Published: January 2022

Background: Biliary atresia (BA) is one of the most common and fatal abnormalities of newborns. Increasing evidences indicated that immunology was the critical part of the etiology. This research used a public gene expression database to explore the immune microenvironment of BA liver.Methods: The gene expression profiles GSE46960, GSE159720, and GSE15235, containing BA and normal liver gene expression data, were obtained from the Expression Omnibus Gene. We applied CIBERSORTx to quantify 22 subsets of immune cells in BA liver. The differentially expressed genes (DEGs) and immune cells were used to further explore their relationship with liver fibrosis and the inflammation status of BA.Results: The expression of immune-related genes CXCL6, CXCL8, CXCL10, CCL20, IL32, TGFB2, SPP1, and SLIT2 was significantly different between BA and normal liver, among which CXCL8 was the hub gene. Six of 22 immune cell proportions were significantly different between BA and normal liver. Specifically, M0 macrophages and resting memory CD4+ T cells were upregulated in BA liver compared with normal liver. Meanwhile, monocytes, resting natural killer (NK) cells, plasma cells, and regulatory T (Treg) cells were downregulated. A further correlation analysis revealed that SLIT2 and CXCL6 owned high positive correlation coefficients with fibrosis grade, while the proportion of resting NK cells was negatively correlated. Proportions of resting CD4+ memory T cells were strongly related to the inflammation grade of BA liver.Conclusion: Biliary atresia is a disease strongly correlated with immune response. Our results might provide a clue for further exploration of BA etiology, which may promote a potential prediction model based on immune infiltration features.
Efficacy and Safety of GHX02 in the Treatment of Acute Bronchitis and Acute Exacerbation of Chronic Bronchitis: A Phase Ⅱ, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial
Authors: Lee Su Won , Lyu Yee Ran , Kim Si Yeon , Yang Won Kyung , Kim Seung Hyung , Kim Ki Mo , Chae Sung-Wook , Kang Weechang , Jung In Chul , Park Yang Chun 
Published: January 2022

Acute bronchitis and acute exacerbations of chronic bronchitis (AECB) have cough and sputum as the main symptoms with a high prevalence and substantial economic burden. Although the demand for bronchitis treatment increases due to causes, such as air pollution, the appropriateness of antibiotic prescriptions and the effects of current symptomatic treatments for bronchitis are unclear. GHX02, which is a combined formulation containing four herbs, and has been clinically used for bronchitis in South Korea. We conducted a phase II, randomized, double-blind, and placebo-controlled, multicenter trial to evaluate its efficacy and safety. Patients with acute bronchitis or AECB were recruited and randomized to receive high-dose GHX02 (1920 mg/day), standard-dose GHX02 (960 mg/day), or placebo for 7 days. The primary outcome measure was the change in Bronchitis Severity Score (BSS) from baseline to Day 7. The secondary outcomes were the frequency of coughing fits, Questionnaire of Clinical Symptoms of Cough and Sputum (QCSCS), Leicester Cough Questionnaire (LCQ), Integrative Medicine Outcome Scale (IMOS), and Integrative Medicine Patient Satisfaction Scale (IMPSS). A total of 117 patients were randomized to parallel groups (38 in the high-dose GHX02, 41 in the standard-dose GHX02 group, and 38 in the placebo group). The mean differences in BSS from baseline to Day 7 in the treatment groups (4.2 ± 2.0 and 4.5 ± 1.8 in the high-dose GHX02 and standard-dose GHX02 groups, respectively) were higher than the placebo group (3.8 ± 2.1), p = 0.028. The mean differences in the frequency of coughing fits from baseline to Day 7 and IMPSS were better in the GHX02 treatment group than in the placebo group (standard-dose GHX02 group vs placebo group, p = 0.036). The QCSCS, LCQ, IMOS, and GHX02 of the treatment groups also showed more improvement than the placebo group, but there were no statistically significant differences between the groups. There were no severe adverse effects during the trial. This study supports that GHX02 is effective and safe for patients with bronchitis and provides the basis for progression to a phase III study.Clinical Trial Registration: [https://cris.nih.go.kr] WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003665].