bluuebunny/crossref_metadata_2025_split huggingface dataset:
Availability of Safe Second-trimester Abortion Services in Health Facilities in Accra, Ghana
Authors: Gbagbo Fred Yao , Morhe Renee Aku Sitsofe , Morhe Emmanuel Komla Senanu 
Published: February 2021

Abstract
BackgroundThis study sought to examine providers, methods employed, cost, and other determinants of availability of second-trimester abortion services in health facilities in Accra, Ghana in 2019 to inform policy and program decisions. MethodsA two-stage mixed quantitative and qualitative study designs were employed in the conduct of this study. The first stage was a short interaction of the mystery client with a clinical care provider to identify health facilities that provide second trimester induced abortion, the cost, and referral practices, where the facility did not have the service. The second stage was in-depth interviews of second-trimester abortion care providers and non-providers in various health facilities. For internal validity, it also explored the procedure cost, referral, and other practices at the health facilities included in the study, independent of what was captured in the mystery client survey.ResultsSecond-trimester abortion services in Accra, Ghana are widely unavailable even in most facilities that provided abortion services. Referral policies and practices indicated by the service providers at various facility levels were inadequate. Criminalization of the procedure, social stigma, and fear of complications are the main factors that adversely influence the availability of second-trimester abortion in health facilities in Accra. ConclusionsAlbeit increasing demand for second-trimester abortion in health facilities in Accra, services are not readily available due to the ambiguity of the law, its interpretation, and limited flow of accurate information on providers. Policies and programs that limit access to Second-trimester abortions in Ghana are amendable to ensure safe services.
Outcomes and Prognostic Factors Following High-dose Re-irradiation for Recurrent Lung Cancer
Authors: Tamari Keisuke , Doi Hiroshi , Shiomi Hiroya , Oh Ryoongjin , Ogawa Kazuhiko 
Published: February 2021

Abstract
Background: Re-irradiation is one of the treatment options for recurrence after initial radiotherapy for locally advanced lung cancer. However, the safety and efficacy of high-dose re-irradiation for recurrent lung cancer has yet to be completely understood. This study investigated the outcomes of high-dose re-irradiation for patients with recurrent lung cancer at our clinic.Methods: Data were collected from 36 patients with lung cancer (median age, 68 years) who received high-dose re-irradiation using intensity-modulated radiotherapy for locoregional recurrence after initial radiotherapy in the locally advanced stage. Histology findings showed that 11 (30.6%), 14 (38.9%), and 11 (30.6%) patients had adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, respectively. The interval from initial radiotherapy to re-irradiation was 23.4 months. Local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors, while late toxicities ≥grade3 were evaluated according to the CTCAE ver. 3.0.Results: The median follow-up was 14.6 months. The 1-year LC, PFS, and OS were 74.1%, 45.2%, and 78.7%, respectively. Multivariate analysis showed that histology was a significant prognostic factor for LC (p = 0.02), while histology (p = 0.04) and distant metastasis (p = 0.01) were significant prognostic factors for PFS. Grade 5 late toxicities occurred in 2 patients (5.6%) who exhibited esophageal perforation and bronchial perforation. No other ≥grade3 late toxicities occurred.Conclusion: High-dose re-irradiation for recurrent locally advanced lung cancer was effective and feasible. Lung adenocarcinoma might therefore be a good indication for re-irradiation.
Concurrent Mutations Associated With Trastuzumab-resistance Revealed by Single Cell Sequencing
Authors: Gao Yan , Wu Ning , Wang Shuai , Yang Xue , Wang Xin , Xu Bo 
Published: February 2021

Abstract
Purpose: HER2-positive breast cancer patients benefit from HER2 targeted therapies, among which the most commonly used is trastuzumab. However, acquired resistance typically happens within one year. The cellular heterogeneity of it is less clear. Methods: Here we generated trastuzumab-resistant cells in two HER2-positive breast cancer cell lines, SK-BR-3 and BT-474. Cells at different time points during the resistance induction were examined by exome sequencing to study changes of genomic alterations over time. Single cell targeted sequencing was also used to identify resistance associated concurrent mutations.Results: We found a rapid increase of copy number variation (CNV) regions and gradual accumulation of single nucleotide variations (SNVs). On the pathway level, nonsynonymous SNVs for SK-BR-3 cells were enriched in the MAPK signaling pathway, while for BT-474 cells were enriched in mTOR and PI3K-Akt signaling pathways. However, all of the three signaling pathways were in the downstream of the HER2 kinase. Putative trastuzumab-resistance associated SNVs included AIFM1 P548L and ERBB2 M833R in SK-BR-3 cells, and OR5M9 D230N, COL9A1 R627T, ITGA7 H911Q and ADAMTS19 V451L in BT-474 cells. Single cell targeted sequencing identified several concurrent mutations. By validation, we found that concurrent mutations (AIFM1 P548L and IL1RAPL2 S546C) led to a decrease of trastuzumab sensitivity. Conclusion: Taken together, our study revealed a common pathway level trastuzumab-resistance mechanism for HER2-positive breast cancer cells. In addition, our identification of concurrent SNVs associated with trastuzumab-resistance may be indicative of potential targets for the treatment of trastuzumab-resistant breast cancer patients.
Widening Participation in Medicine: The Impact of Medical Student-led Conferences for Year 12 Pupils
Authors: Ryan Ben , Auty Charlotte , Maden Matthew , Leggett Amy , Staley Alisha , Haque Enam 
Published: February 2021

Abstract
Background Individuals from deprived backgrounds are under-represented in the medical profession: confidence is a barrier to them successfully applying to medical school. Unfortunately, medical school widening participation (WP) initiatives to address this are limited by funding. Methods This study examined the impact of two student-led conferences that Year 12 pupils attended and presented at. It looked at the ability of the conferences to engage WP pupils, their impact on participant confidence, and the feasibility of them being replicated by other student-led groups. The first, Conference A, had more time and finances invested into it than the second, Conference B. The latter relied solely on university society funding, but utilised WP criteria for selection of participants. Participants identified their confidence in six areas on a ten-point scale, immediately before and after the intervention. Results A paired t-test showed a significant improvement (p < 0.01) in all areas of confidence for both conferences. Cohen’s d showed Conference A had larger effect sizes in five out of six areas than Conference B. Conclusion This intervention has demonstrated a significant impact on participant confidence: a key factor to improve their chance of successful admission to medical school. This impact may be enhanced by supporting participants with their presentations prior to the conference; it is feasible for this work to be replicated by other student-led groups.
A human mutation in STAT3 promotes type 1 diabetes through a defect in CD8+ T cell tolerance
Authors: Anderson Mark , Warshauer Jeremy , Belk Julia , Chan Alice , Wang Jiaxi , Gupta Alexander , Acenas Dante , Shi Quanming , Peng Yani , Phipps Jonah , Tang Qizhi , Gardner James , Satpathy Ansuman 
Published: February 2021

Abstract
Naturally occurring cases of monogenic type 1 diabetes (T1D) provide rare opportunities to establish direct mechanisms that cause this complex autoimmune disease. A recently identified de novo germline gain-of-function (GOF) mutation in the transcriptional regulator signal transducer and activator of transcription 3 (STAT3) was shown to cause neonatal T1D at birth. To investigate the role of STAT3 hyperactivity in T1D, we engineered a novel knock-in (KI) mouse incorporating this highly diabetogenic human mutation (K392R) in the STAT3 gene. These mice developed accelerated diabetes with severe insulitis and insulin autoantibodies, thereby recapitulating the human autoimmune diabetes phenotype. Paired T cell receptor (TCR) and transcriptome (RNA) sequencing in single cells revealed that STAT3-GOF drives the proliferation and clonal expansion of highly cytotoxic effector CD8+ T cells that are resistant to terminal exhaustion. Single-cell ATAC-seq showed that these effector T cells are epigenetically distinct and revealed differential chromatin architecture induced by STAT3-GOF. Analysis of islet TCR clonotypes revealed an effector CD8+ T cell reacting against the known antigen IGRP, and STAT3-GOF in an IGRP-reactive TCR transgenic model demonstrated that STAT3-GOF intrinsic to CD8+ T cells is sufficient to accelerate diabetes onset. Taken together, these findings reveal a diabetogenic CD8+ T cell response that is restrained in the presence of normal STAT3 activity and drives diabetes pathogenesis.
Comparison of different lignocellulosic biomass for Solvent production by Clostridium beijerinckii strains
Authors: Dalal Jyotsana , Joy Sam , Das Mriganko , Rawat Jaya 
Published: February 2021

Abstract
The aim of the present study was to compare the effect of lignocellulosic sugar hydrolysate, obtained after acid pretreatment of different lignocellulosic biomass on production of solvents by two different Clostridium beijerinckii strains. C. beijerinckii C-01 produced solvents via the isopropanol-butanol-ethanol (IBE) pathway and C. beijerinckii B-17 via the acetone-butanol-ethanol (ABE). The hydrolysate was obtained after acid pretreatment of rice-husk, rice-straw and sugarcane-bagasse. Solvent production was observed from all the three substrates by both the strains. However, the highest solvent production of 9.2 gL− 1 similar to medium supplemented with commercial sugars was observed in sugarcane-bagasse hydrolysate by C. beijerinckii B-17. Degradation products i.e. 5-Hydroxy-methyl-furfural, levulinic acid, furfural and formic acid were found in different concentrations during acid pretreatments. The highest amount of formic acid (3.5 gL− 1), along with significant amounts of levulinic acid and furfural, was found to be present in rice-husk hydrolysate. The study shows that rice-straw and sugarcane-bagasse obtained after acid pretreatment are better substrates in comparison to rice-husk for butanol production by Clostridium beijerinckii strains.
An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT
Authors: LI JIE , Wang Yuegang , Mai Jingting , Chen Shilan , Liu Menghui , Su Chen , Chen Xumiao , Huang Huiling , Ma Yuedong , Feng Chong , Jiang Jingzhou , Liu Jun , He Jiangui , Tang Anli , Dong Yugang , Huang Xiaobo , Chen Yangxin , Wang Lichun 
Published: February 2021

Abstract
Background:Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be in discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to get the maximum integrative effects of AV and ventricular resynchronization (opt-AV).Methods:Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was <20ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was >20ms.Results:The results showed sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/ Pend-Ap)( P＜0.05 ). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) were correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P＜0.01). The percentages of patients with more than 20ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, the opt-AV were linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV)=0.1×SAVopt-AV+0.4×SAVopt-V+70ms (R2=0.665, P<0.01) and the pacing opt-AV (opt-PAV)=0.25×PAVopt-AV+0.5×PAVopt-V+30ms (R2=0.560, P<0.01).Conclusion:The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of patients had a >20ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.
Antioxidant and beta-Galactosidase Inhibitory Studies of Methanolic Extract of Juniperus Phoenicea and Calicotome Villosa from Jordan
Authors: Al-Mustafa Ahmed , Al-Tawarah Mohammad , Al-Sheraideh Mohammed Sharif , Al-Zahrany Fatima Attia 
Published: February 2021

Abstract
Background: We investigated Juniperus Phoenicea (J. Phoenicea) and Calicotome Villosa (C. Villosa) from Jordan for phenolic contents, antioxidant, anti β-Galactosidase activities, in an attempt to rationalize its use in lactose metabolism disorders. The kinetic parameters of leave extracts, galactose, glucose, fructose and acarbose were evaluated. Also, the thermodynamic parameters of the enzyme thermal inactivation were determined. Methods: JP and cv crude methanolic extracts were evaluated for 1,1-diphenyl,2-picrylhydrazyl (DPPH) free radical scavenging activity and ferric reducing antioxidant power (FRAP). Further, β-Galactosidase inhibitory activities were performed using O-nitrophenyl-beta-D-galactopyranoside as substrate. Moreover, total phenolic contents, flavonoids and flavonols of plants extracts were determined and expressed in mg of gallic acid equivalent (mg GAE/g dry extract) or rutin equivalent per gram of dry extract (mg RE/g dry extract).Results: Phytochemical screening of the crude extract of J. Phoenicea and C. Villosa leaves contained phenols, alkaloids, flavonoids, terpenoids, anthraquinones and glycosides. J. Phoenicea exhibited high flavonoids and flavonols contents than C. Villosa but both J. Phoenicea and C. Villosa contained high phenolic and showed concentration dependent DPPH scavenging activity, with J. Phoenicea (IC50 =11.1 μg/ml), C. Villosa (IC50 =15.6 μg/ml), respectively. According to FRAP assay, the antioxidant power activity of plants extracts was concentrations dependent. The β-galactosidase % inhibition was increased as the concentration of of J. phoenicea, C. villosa and rutin increased. The mode of inhibition of β-galactosidase by J. phoenicea (IC50= 65 µg/ml) and C. villosa (IC50= 700 µg/ml) extracts was non-competitive and mixed-inhibition, respectively. Also, rutin was affected in a competitive (IC50 = 75 µg/ml) inhibition. β-galactosidase half-life was 108 min at 55°C, thermodynamic parameters revealed an activation energy of 208.88 kJ mol-1 and the inactivation kinetic follows a first-order reaction with k-values ranges between 0.0862 and 0.0023 min-1. The enzyme showing a decreasing trend of enthalpy of denaturation (∆H°) as temperature increase but value of free energy of thermal denaturation (∆G°) for β-galactosidase was decreased with increasing in temperature. The calculated entropy of inactivation (∆S°) at each temperature showed positive values, which means there are no significant processes of aggregation.Conclusions: J.phoenicea and C.villosa have inhibiting effect on β-galactosidase activity. Thermodynamic approach shows an enzyme stable and suggests that inactivation mechanism is based on molecular structural changes.
Oral Vitamin D Supplementation does not Impact Cytokine Levels in Uterine Fluid of Women Undergoing Assisted Reproduction Technology (ART)
Authors: Cermisoni Greta Chiara , Reschini Marco , Piccinni Marie-Pierre , Lombardelli Letizia , Logiodice Federica , Sarais Veronica , Giacomini Elisa , Signorelli Simona , Somigliana Edgardo , Viganò Paola 
Published: February 2021

Abstract
Background: Cytokines and chemokines, secreted in the intrauterine environment, are fundamental for the molecular crosstalk between endometrium and preimplantation embryo. Whether Vitamin D can have a beneficial effect on endometrial district and immune cells is still unclear. To fill this gap, the aim of this study was to explore if Vitamin D supplementation can act on intrauterine milieu as immuno-modulator. Methods: We present a report of a secondary outcome from the SUNDRO clinical trial, a multi-center randomized double-blinded trial aimed to explore the effects of Vitamin D replacement (a single dose of 600,000 IU of 25-hydroxy Vitamin D or placebo) in insufficient women undergoing autologous ART cycles. Inclusion criteria were female age between 18-39 years, with body mass index between 18 and 25 Kg/m2. Uterine fluid samples were collected during the secretory phase of the menstrual cycle that proceeded the oocyte retrieval. The quantitative determination of twenty-seven cytokines in endometrial secretion samples was performed by using a multiplex immunoassay.Results: Forty-nine uterine fluid samples (UF) were collected during the secretory phase of the menstrual cycle prior to oocyte retrieval. Our data revealed no differences in UF composition of Vitamin D supplemented women (n=17) compared with the placebo group (n=32), also when protein normalization was performed. In addition, no significant differences were found in mediators relative content of UFs from women who conceived (n=19) compared with the non-pregnant group (n=30). Conclusions: The explored in vivo vitamin D replacement regimen is unlikely to directly influence the cytokine and chemokine endometrial milieu. EudraCT registration number: 2015-004233-27.
Differential Circular RNA Expression Profiles in Umbilical Cord Blood Exosomes from Preeclampsia Patients
Authors: Cao Minkai , Wen Juan , Bu Chaozhi , Li Chunyan , Lin Yu , Zhang Hong , Gu Yanfang , Shi Zhonghua , Zhang Yan , Long Wei , Zhang Le 
Published: February 2021

Abstract
Exosomal circular RNAs (circRNAs) are emerging as important regulators of physiological development and disease pathogenesis. However, the roles of exosomal circRNAs from umbilical cord blood in preeclampsia (PE) occurrence remains poorly understood. In this study, we used microarray technology to establish the differential circRNA expression profiles in umbilical cord blood exosomes from PE patients compared with normal controls. According to the microarray data, we identified 143 significantly up-regulated circRNAs and 161 significantly down-regulated circRNAs in umbilical cord blood exosomes of PE patients compared with controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses demonstrated that circRNA parental genes involved in the regulation of metabolic process, trophoblast growth and invasion were significantly enriched, which are important in PE development. Moreover, pathway network was constructed to reveal the key pathways in PE, such as PI3K-Akt signaling pathway. Further circRNA/miRNA interactions analysis showed that most of the exosomal circRNAs harbored miRNA binding sites, and some miRNAs were associated with PE. Collectively, our results highlight the importance of exosomal circRNAs in the pathogenesis of PE and lay a foundation for extensive studies on the role of exosomal circRNAs in PE development.
Ultrasonographic Study of Fetal Facial Profile Markers During First Trimester
Authors: Ji Chunya , Zhao Qiaomei , Yin Linliang , Deng Xuedong , Yang Zhong , Pan Qi , Zhang Jun , Jiang Xiaoli , Liang Qing 
Published: February 2021

Abstract
Background: To establish normal reference ranges of fetal facial profile markers, and to study their correlation with crown-rump length (CRL) during first trimester (11~13+6 weeks’ gestation) in a Han Chinese population. Methods: Ultrasonographic images of measuring fetal nuchal translucency (NT) were retrospectively selected randomly in normal pregnancies where both parents were of Han Chinese ethnicity. The facial markers included inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial maxillary angle (FMA) and profile line (PL) distance. These markers were measured through ViewPoint 6 software by two experienced sonographers.Results: Three hundred and eighty fetuses were selected. The ICCs (95% CI) of intra-operator 1 reproducibility of IFA, MNM angle, FMA, PL distance were 0.944 (0.886~0.973), 0.804 (0.629~0.902), 0.834 (0.68~0.918) and 0.935 (0.868~0.969), respectively. The ICCs (95% CI) of intra-operator 2 reproducibility of IFA, MNM angle, FMA, PL distance were 0.931 (0.857~0.967), 0.809 (0.637~0.904), 0.786 (0.600~0.892) and 0.906 (0.813~0.954), respectively. The ICCs (95% CI) of inter-operator reproducibility of IFA, MNM angle, FMA, PL distance were 0.885 (0.663~0.953), 0.829 (0.672~0.915), 0.77 (0.511~0.891) and 0.844 (0.68~0.925), respectively. The average±SD of IFA, MNM angle, FMA and PL distance were 80.2°±7.25°, 4.17°±1.19°, 75.36°±5.31°, 2.78±0.54 mm, respectively. IFA and PL distance significantly decreased with CRL, while MNM angle and FMA significantly increased with CRL.Conclusion: It was feasible to measure fetal facial markers during first trimester. The normal range of each marker was obtained through large sample data, and the measurements were found to correlate with CRL.