bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway
Authors: Yang Ye , Liu Ping Yin , Bao Wei , Chen Song Jun , Wu Fang Su , Zhu Ping Ya 
Published: January 2020

Abstract
Background
Pyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis.

Methods
We performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1β ELISA were used to analysis pyroptosis between hydrogen-supplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation.

Results
We observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosis-related proteins, and increased the number of PI- and TUNEL-positive cells, as well as the release of LDH and IL-1β, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway.

Conclusions
This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.
Mortality after hospital admission for heart failure: improvement over time, equally strong in women as in men
Authors:   on behalf of the Queen of Hearts and RECONNECT investigators, Buddeke J. , Valstar G. B. , van Dis I. , Visseren F. L. J. , Rutten F. H. , den Ruijter H. M. , Vaartjes I. , Bots M. L. 
Published: January 2020

Abstract
Background
To assess the trend in age- and sex-stratified mortality after hospitalization for heart failure (HF) in the Netherlands.

Methods
Two nationwide cohorts of patients, hospitalized for new onset heart failure between 01.01.2000–31.12.2002 and between 01.01.2008–31.12.2010, were constructed by linkage of the Dutch Hospital Discharge Registry and the National Cause of Death registry. 30-day, 1-year and 5 -year overall and cause-specific mortality rates stratified by age and sex were assessed and compared over time.

Results
We identified 40,230 men and 41,582 women. In both cohorts, men were on average younger than women (74–75 and 78–79 years, respectively) and more often had comorbid conditions (37 and 30%, respectively). In the 2008–10 cohort, mortality rates for men were 13, 32 and 64% for respectively 30-day, 1-year and 5-year mortality and 14, 33 and 66% for women. Mortality rates increased considerably with age similarly in men and women (e.g. from 10.5% in women aged 25–54 to 46.1% in those aged 85 and older after 1 year). Between the two time periods, mortality rates dropped across all ages, equally strong in women as in men. The 1-year absolute risk of death declined by 4.0% (from 36.1 to 32.1%) in men and 3.2% (from 36.2 to 33.0%) in women.

Conclusions
Mortality after hospitalization for new onset HF remains high, however, both short-term and long-term survival is improving over time. This improvement was similar across all ages and equally strong in women as in men.
Refusals to perform ritual circumcision: a qualitative study of doctors’ professional and ethical reasoning
Authors: Litleskare Liv Astrid , Strander Mette Tolås , Førde Reidun , Magelssen Morten 
Published: January 2020

Abstract
Background
Ritual circumcision of infant boys is controversial in Norway, as in many other countries. The procedure became a part of Norwegian public health services in 2015. A new law opened for conscientious objection to the procedure. We have studied physicians’ refusals to perform ritual circumcision as an issue of professional ethics.

Method
Qualitative interview study with 10 urologists who refused to perform ritual circumcision from six Norwegian public hospitals. Interviews were recorded and transcribed, then analysed with systematic text condensation, a qualitative analysis framework.

Results
The physicians are unanimous in grounding their opposition to the procedure in professional standards and norms, based on fundamental tenets of professional ethics. While there is homogeneity in the group when it comes to this reasoning, there are significant variations as to how deeply the matter touches the urologists on a personal level. About half of them connect their stance to their personal integrity, and state that performing the procedure would go against their conscience and lead to pangs of conscience.

Conclusions
It is argued that professional moral norms sometimes might become more or less ‘integrated’ in the professional’s core moral values and moral identity. If this is the case, then the distinction between conscience-based and professional refusals to certain healthcare services cannot be drawn as sharply as it has been.
Improving emergency obstetric referral systems in low and middle income countries: a qualitative study in a tertiary health facility in Ghana
Authors: Daniels Anita Anima , Abuosi Aaron 
Published: January 2020

AbstractBackgroundTimely access to emergency obstetric care is crucial in preventing mortalities associated with pregnancy and childbirth. The referral of patients from lower levels of care to higher levels has been identified as an integral component of the health care delivery system in Ghana. To this effect, in 2012, the National Referral Policy and Guidelines was developed by the Ministry of Health (MOH) to help improve standard procedures and reduce delays which affect access to emergency care. Nonetheless, ensuring timely access to care during referral of obstetric emergencies has been problematic. The study aimed to identify barriers associated with the referral of emergency obstetric cases to the leading national referral centre. It specifically examines the lived experiences of patients, healthcare providers and relatives of patients on the referral system.MethodsKorle Bu Teaching Hospital, Accra was used as a case study in 2016.The qualitative method was used and in-depth interviews were conducted with 89 respondents: healthcare providers [n = 34];patients [n = 31] and relatives of patients [n = 24] using semi-structured interview guides. Purposive sampling techniques were used in selecting healthcare providers and patients and convenience sampling techniques were used in selecting relatives of patients.ResultsThe study identified a range of barriers encountered in the referral process and broadly fall under the major themes: referral transportation system, referrer-receiver communication barriers, inadequate infrastructure and supplies and insufficient health personnel. Some highlights of the problem included inadequate use of ambulance services, poor management of patients during transit, lack of professional escort, unannounced emergency referrals, lack of adequate information and feedback and limited supply of beds, drugs and blood. These findings have implications on type II and III of the three delays model.ConclusionsInitiatives to improve the transportation system for the referral of obstetric emergencies are vital in ensuring patients’ safety during transfer. Communication between referring and receiving facilities should be enhanced. A strong collaboration is needed between teaching hospitals and other stakeholders in the referral chain to foster good referral practices and healthcare delivery. Concurrently, supply side barriers at referred facilities including ensuring sufficient provision for bed, blood, drugs, and personnel must be addressed.
Clinical isolates of Tritrichomonas foetus in bulls in Wyoming, South Dakota and Montana, USA
Authors: Jin Yinzhu , Du Aifang , Yao Chaoqun 
Published: January 2020

Abstract
Background
Several Tritrichomonas species have been found in mammalian hosts. Among these trichomonads T. foetus is often found in the urogenital tract of cattle and the gastrointestinal tract of the domestic cat, resulting in sexually transmitted bovine trichomonosis and fecal-orally transmitted feline trichomonosis, respectively. The aims of the current study were to molecularly characterize clinical isolates of T. foetus in cattle populations in Wyoming, South Dakota, and Montana of the United States of America and to phylogenetically analyze Tritrichomonas species of mammalian hosts.

Results
DNA sequencing of rRNA genes showed over 99% identity of the newly described isolates to other bovine isolates. Further, T. foetus isolates of various mammalian hosts originated in different geographic regions worldwide were clustered into two well-defined clades by phylogenetic analysis of rRNA and cysteine protease 2 genes. Clade I consisted of isolates originated from cattle, pig, and human whereas clade II contained isolates of cat and dog.

Conclusion
It is concluded that all mammalian Tritrichomonas spp. apparently belong to T. foetus. Analysis of more sequences is warranted to support this conclusion.
Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs
Authors: Liao Yifang , Li Ping , Wang Yanxia , Chen Hong , Ning Shangwei , Su Dongju 
Published: January 2020

Abstract
Background
Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis.

Methods
Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma.

Results
This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide).

Conclusions
The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.
The stability of blood Eosinophils in chronic obstructive pulmonary disease
Authors: Long Gabriella H. , Southworth Thomas , Kolsum Umme , Donaldson Gavin C. , Wedzicha Jadwiga A. , Brightling Christopher E. , Singh Dave 
Published: January 2020

AbstractBlood eosinophils are a predictive biomarker of inhaled corticosteroid response in chronic obstructive pulmonary disease (COPD). We investigated blood eosinophil stability over 1 year using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 thresholds of < 100, 100- < 300 and ≥ 300 eosinophils/μL in 225 patients from the COPDMAP cohort. Blood eosinophils showed good stability (rho: 0.71, p < 0.001, ICC 0.84), and 69.3% of patients remained in the same eosinophil category at 1 year. 85.3% of patients with eosinophils < 100 cells/μL had stable counts. The majority of blood eosinophil counts remain stable over 1 year using the GOLD 2019 thresholds.
Silencing of miR-17-5p suppresses cell proliferation and promotes cell apoptosis by directly targeting PIK3R1 in laryngeal squamous cell carcinoma
Authors: Wang Jian-Xing , Jia Xin-Ju , Liu Yan , Dong Jin-Hui , Ren Xiu-Min , Xu Ou , Liu Sheng-Hui , Shan Chun-Guang 
Published: January 2020

Abstract
Background
Increasing evidence has suggested that microRNAs (miRNAs) act as key post-transcriptional regulators in tumor progression. Previous studies have confirmed that miR-17-5p functions as an oncogene in multiple cancers and contributes to tumor progression. However, the role and biological functions of miR-17-5p in the development of laryngeal squamous cell carcinoma (LSCC) still remain unknown.

Methods
qRT-PCR was used to detect miRNA and mRNA expression levels in LSCC tissues and cell lines. CCK-8 assay was used to measure cell viability and flow cytometry was performed to evaluate cell apoptosis. Western blot analysis was used to detect the protein levels of BAX, BCL-2, cleaved Caspase-3, PIK3R1 and AKT. Luciferase reporter assay was used to detect the effect of miR-17-5p on PIK3R1 expression. Xenograft animal model was used to test the effect of miR-17-5p on LSCC cell in vivo.

Results
In the present study, we found that miR-17-5p expression level was upregulated in LSCC tissues and cell lines. Depletion of miR-17-5p in LSCC cells significantly reduced cell proliferation and promoted cell apoptosis in vitro and in vivo. Mechanically, knockdown of miR-17-5p in LSCC cells inhibited BCL-2 expression while enhanced BAX and cleaved Caspase-3 protein expression. Moreover, depletion of miR-17-5p in LSCC cells suppressed AKT phosphorylation but did not influence PTEN expression. Importantly, miR-17-5p positively regulated PIK3R1 expression by directly binding to its 3′-untranslated region (UTR). Additionally, PIK3R1, which expression was downregulated in LSCC tissues and cell lines, was involved in LSCC cell survival by modulating the activation of AKT signal pathway. Dysregulation of miR-17-5p/PIK3R1 axis was participated in LSCC cell proliferation and apoptosis by inhibiting the activation of the PI3K/AKT signaling pathway.

Conclusions
In conclusion, our study indicates that the miR-17-5p/PIK3R1 axis plays an essential role in the development of LSCC and provides a potential therapeutic target for LSCC treatment.
Delayed frozen embryo transfer failed to improve live birth rate and neonatal outcomes in patients requiring whole embryo freezing
Authors: He Yuxia , Zheng Haiyan , Du Hongzi , Liu Jianqiao , Li Lei , Liu Haiying , Cao Mingzhu , Chen Shiping 
Published: January 2020

Abstract
Background
Controlled ovarian stimulation (COS) has a negative effect on the endometrial receptivity compared with natural menstrual cycle. Whether it’s necessary to postpone the first frozen embryo transfer (FET) following a freeze-all strategy in order to avoid any residual effect on endometrial receptivity consequent to COS was inconclusive.

Objective
The purpose of this retrospective study was to explore whether the delayed FET improve the live birth rate and neonatal outcomes stratified by COS protocols after a freeze-all strategy.

Methods
A total of 4404 patients who underwent the first FET cycle were enrolled in this study between April 2014 to December 2017, and were divided into immediate (within the first menstrual cycle following withdrawal bleeding) or delayed FET (waiting for at least one menstrual cycle and the transferred embryos were cryopreserved for less than 6 months). Furthermore, each group was further divided into two subgroups according to COS protocols, and the pregnancy and neonatal outcomes were analyzed between the immediate and delayed FET following the same COS protocol.

Results
When FET cycles following the same COS protocol, there was no significant difference regarding the rates of live birth, implantation, clinical pregnancy, multiple pregnancy, early miscarriage, premature birth and stillbirth between immediate and delayed FET groups. Similarly, no significant differences were found for the mean gestational age, the mean birth weight, and rates of low birth weight and very low birth weight between the immediate and delayed FET groups. The sex ratio (male/female) and the congenital anomalies rate also did not differ significantly between the two FET groups stratified by COS protocols.

Conclusion
Regardless of COS protocols, FET could be performed immediately after a freeze-all strategy for delaying FET failed to improve reproductive and neonatal outcomes.
The potential therapeutic effects of the gut microbiome manipulation by synbiotic containing-Lactobacillus plantarum on neuropsychological performance of diabetic rats
Authors: Morshedi Mohammad , Saghafi-Asl Maryam , Hosseinifard Elaheh-Sadat 
Published: January 2020

Abstract
Background
The manipulation of gut microbiota as a target has been suggested to reduce the risks for a number of diseases such as type 2 diabetes mellitus (T2DM). Conversely, T2DM is associated with complications such as gut and brain disorders. Furthermore, the impact of probiotics and prebiotics to improve T2DM complications are reported. Thus, the present study seeks to investigate the therapeutic and neuropsychological effects of L. plantarum and inulin in diabetic rats.

Methods
Throughout the investigation, L. plantarum, inulin or their combination (synbiotic) was administered to diabetic rats. in the end, fecal samples were collected to evaluate the gut microbial composition. Then behavioral tests were conducted. Subsequently, the obtainment of the prefrontal cortex (PFC) and hippocampal samples.

Results
Our data demonstrated that administration of L. plantarum and inulin could improve gut dysbiosis and oxidative stress status. In addition, it could ameliorate serotonin and BDNF/TrkB signaling pathway. Notably, a strong correlation between the gut microbiota changes and cognition responses was observed. Interestingly, synbiotics intake exploited a rather powerful effect on oxidative stress markers.

Conclusion
The findings confirm that there is a beneficial therapeutic potential of supplements, especially symbiotic. Moreover, neuropsychological improvement associated with balanced gut microbiome.
Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass
Authors: Raggi Federica , Cangelosi Davide , Becherini Pamela , Blengio Fabiola , Morini Martina , Acquaviva Massimo , Belli Maria Luisa , Panizzon Giuseppe , Cervo Giuseppe , Varesio Luigi , Eva Alessandra , Bosco Maria Carla 
Published: January 2020

Abstract
Background
Tetralogy of Fallot (ToF) and Atrial Septal Defects (ASD) are the most common types of congenital heart diseases and a major cause of childhood morbidity and mortality. Cardiopulmonary bypass (CPB) is used during corrective cardiac surgery to support circulation and heart stabilization. However, this procedure triggers systemic inflammatory and stress response and consequent increased risk of postoperative complications. The aim of this study was to define the molecular bases of ToF and ASD pathogenesis and response to CPB and identify new potential biomarkers.

Methods
Comparative transcriptome analysis of right atrium specimens collected from 10 ToF and 10 ASD patients was conducted before (Pre-CPB) and after (Post-CPB) corrective surgery. Total RNA isolated from each sample was individually hybridized on Affymetrix HG-U133 Plus Array Strips containing 38,500 unique human genes. Differences in the gene expression profiles and functional enrichment/network analyses were assessed using bioinformatic tools. qRT-PCR analysis was used to validate gene modulation.

Results
Pre-CPB samples showed significant differential expression of a total of 72 genes, 28 of which were overexpressed in ToF and 44 in ASD. According to Gene Ontology annotation, the mostly enriched biological processes were represented by matrix organization and cell adhesion in ToF and by muscle development and contractility in ASD specimens. GSEA highlighted the specific enrichment of hypoxia gene sets in ToF samples, pointing to a role for hypoxia in disease pathogenesis. The post-CPB myocardium exhibited significant alterations in the expression profile of genes related to transcription regulation, growth/apoptosis, inflammation, adhesion/matrix organization, and oxidative stress. Among them, only 70 were common to the two disease groups, whereas 110 and 24 were unique in ToF and ASD, respectively. Multiple functional interactions among differentially expressed gene products were predicted by network analysis. Interestingly, gene expression changes in ASD samples followed a consensus hypoxia profile.

Conclusion
Our results provide a comprehensive view of gene reprogramming in right atrium tissues of ToF and ASD patients before and after CPB, defining specific molecular pathways underlying disease pathophysiology and myocardium response to CPB. These findings have potential translational value because they identify new candidate prognostic markers and targets for tailored cardioprotective post-surgical therapies.