bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOXO1 mitigates the SMAD3/FOXL2C134W transcriptomic effect in a model of human adult granulosa cell tumor
Authors: Secchi Christian , Benaglio Paola , Mulas Francesca , Belli Martina , Stupack Dwayne , Shimasaki Shunichi 
Published: February 2021

Abstract
Background
Adult granulosa cell tumor (aGCT) is a rare type of stromal cell malignant cancer of the ovary characterized by elevated estrogen levels. aGCTs ubiquitously harbor a somatic mutation in FOXL2 gene, Cys134Trp (c.402C < G); however, the general molecular effect of this mutation and its putative pathogenic role in aGCT tumorigenesis is not completely understood. We previously studied the role of FOXL2C134W, its partner SMAD3 and its antagonist FOXO1 in cellular models of aGCT.

Methods
In this work, seeking more comprehensive profiling of FOXL2C134W transcriptomic effects, we performed an RNA-seq analysis comparing the effect of FOXL2WT/SMAD3 and FOXL2C134W/SMAD3 overexpression in an established human GC line (HGrC1), which is not luteinized, and bears normal alleles of FOXL2.

Results
Our data shows that FOXL2C134W/SMAD3 overexpression alters the expression of 717 genes. These genes include known and novel FOXL2 targets (TGFB2, SMARCA4, HSPG2, MKI67, NFKBIA) and are enriched for neoplastic pathways (Proteoglycans in Cancer, Chromatin remodeling, Apoptosis, Tissue Morphogenesis, Tyrosine Kinase Receptors). We additionally expressed the FOXL2 antagonistic Forkhead protein, FOXO1. Surprisingly, overexpression of FOXO1 mitigated 40% of the altered genome-wide effects specifically related to FOXL2C134W, suggesting it can be a new target for aGCT treatment.

Conclusions
Our transcriptomic data provide novel insights into potential genes (FOXO1 regulated) that could be used as biomarkers of efficacy in aGCT patients.
Assessment of midwifery care providers intrapartum care competencies, in four sub-Saharan countries: a mixed-method study protocol
Authors: Moller Ann-Beth , Welsh Joanne , Gross Mechthild M. , Petzold Max , Ayebare Elizabeth , Chipeta Effie , Hounkpatin Hashim , Kandeya Bianca , Mwilike Beatrice , Sognonvi Antoinette , Hanson Claudia 
Published: February 2021

Abstract
Background
We aim to assess competencies (knowledge, skills and attitudes) of midwifery care providers as well as their experiences and perceptions of in-service training in the four study countries; Benin, Malawi, Tanzania and Uganda as part of the Action Leveraging Evidence to Reduce perinatal mortality and morbidity in sub-Saharan Africa project (ALERT). While today more women in low- and middle-income countries give birth in health care facilities, reductions in maternal and neonatal mortality have been less than expected. This paradox may be explained by the standard and quality of intrapartum care provision which depends on several factors such as health workforce capacity and the readiness of the health system as well as access to care.

Methods
Using an explanatory sequential mixed method design we will employ three methods (i) a survey will be conducted using self-administered questionnaires assessing knowledge, (ii) skills drills assessing basic intrapartum skills and attitudes, using an observation checklist and (iii) Focus Group Discussions (FGDs) to explore midwifery care providers’ experiences and perceptions of in-service training. All midwifery care providers in the study facilities are eligible to participate in the study. For the skills drills a stratified sample of midwifery care providers will be selected in each hospital according to the number of providers and, professional titles and purposive sampling will be used for the FGDs. Descriptive summary statistics from the survey and skills drills will be presented by country. Conventional content analysis will be employed for data analysis of the FGDs.

Discussion
We envision comparative insight across hospitals and countries. The findings will be used to inform a targeted quality in-service training and quality improvement intervention related to provision of basic intrapartum care as part of the ALERT project.
Trial registration: PACTR202006793783148—June 17th, 2020.
Inhibitors of endosomal acidification suppress SARS-CoV-2 replication and relieve viral pneumonia in hACE2 transgenic mice
Authors: Shang Chao , Zhuang Xinyu , Zhang He , Li Yiquan , Zhu Yilong , Lu Jing , Ge Chenchen , Cong Jianan , Li Tingyu , Tian Mingyao , Jin Ningyi , Li Xiao 
Published: February 2021

Abstract
Background
Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and broke out as a global pandemic in late 2019. The acidic pH environment of endosomes is believed to be essential for SARS-CoV-2 to be able to enter cells and begin replication. However, the clinical use of endosomal acidification inhibitors, typically chloroquine, has been controversial with this respect.

Methods
In this study, RT-qPCR method was used to detect the SARS-CoV-2N gene to evaluate viral replication. The CCK-8 assay was also used to evaluate the cytotoxic effect of SARS-CoV-2. In situ hybridization was used to examine the distribution of the SARS-CoV-2 gene in lung tissues. Hematoxylin and eosin staining was also used to evaluate virus-associated pathological changes in lung tissues.

Results
In this study, analysis showed that endosomal acidification inhibitors, including chloroquine, bafilomycin A1 and NH4CL, significantly reduced the viral yields of SARS-CoV-2 in Vero E6, Huh-7 and 293T-ACE2 cells. Chloroquine and bafilomycin A1 also improved the viability and proliferation of Vero E6 cells after SARS-CoV-2 infection. Moreover, in the hACE2 transgenic mice model of SARS-CoV-2 infection, chloroquine and bafilomycin A1 reduced viral replication in lung tissues and alleviated viral pneumonia with reduced inflammatory exudation and infiltration in peribronchiolar and perivascular tissues, as well as improved structures of alveolar septum and pulmonary alveoli.

Conclusions
Our research investigated the antiviral effects of endosomal acidification inhibitors against SARS-CoV-2 in several infection models and provides an experimental basis for further mechanistic studies and drug development.
Health impact of acute intermittent porphyria in latent and non-recurrent attacks patients
Authors: Buendía-Martínez Juan , Barreda-Sánchez María , Rodríguez-Peña Lidya , Ballesta-Martínez María Juliana , López-González Vanesa , Sánchez-Soler María José , Serrano-Antón Ana Teresa , Pérez-Tomás María Elena , Gil-Ferrer Remedios , Avilés-Plaza Francisco , Glover-López Guillermo , Carazo-Díaz Carmen , Guillén-Navarro Encarna 
Published: February 2021

Abstract
Background
Acute intermittent porphyria (AIP) is a genetic disease characterized by acute neurovisceral attacks. Long-term clinical conditions, chronic symptoms and impaired health related quality of life (HRQoL) have been reported during non-attack periods but mainly in patients with recurrent attacks. Our aim was to investigate these aspects in sporadic AIP (SA-AIP) and latent AIP (L-AIP) patients. Fifty-five participants, 27 SA-AIP (< 4 attacks/year) and 28 L-AIP patients with a prevalent founder mutation from Spain were included. Medical records were reviewed, and individual interviews, physical examinations, biochemical analyses, and abdominal ultrasound scans were conducted. HRQoL was assessed through an EQ-5D-5L questionnaire. A comparative study was made between SA-AIP and L-AIP patients.

Results
The earliest long-term clinical condition associated with SA-AIP was chronic kidney disease. Chronic symptoms were reported in 85.2 % of SA-AIP and 46.4 % of L-AIP patients. Unspecific abdominal pain, fatigue, muscle pain and insomnia were significantly more frequent in SA-AIP than in L-AIP patients. The EQ-5D-5L index was lower in SA-AIP (0.809 vs. 0.926, p = 0.0497), and the impact of “pain”, “anxiety-depression” and “mobility” was more intense in the EQ-5D-5L domains in SA-AIP than in L-AIP subjects and the general Spanish population.

Conclusions
AIP remains a chronically symptomatic disease that adversely affects health and quality of life, even in patients with low rate of acute attacks. We suggest a regular monitoring of patients with symptomatic AIP regardless of their attack rate or the time since their last attack, with proper pain management and careful attention to kidney function.
Monitoring of up to 15 years effects of lipoprotein apheresis on lipids, biomarkers of inflammation, and soluble endoglin in familial hypercholesterolemia patients
Authors: Víšek J. , Bláha M. , Bláha V. , Lášticová M. , Lánska M. , Andrýs C. , Tebbens J. Duintjer , Igreja e Sá Ivone Cristina , Tripská K. , Vicen M. , Najmanová I. , Nachtigal P. 
Published: February 2021

AbstractBackgroundLipoprotein apheresis (LA) is considered as an add-on therapy for patients with familial hypercholesterolemia (FH). We aimed to analyze the data collected in the last 15 years from FH patients treated with LA, to elucidate the benefit of this procedure with respect to plasma lipids, biomarkers of inflammation, and endothelial dysfunction and soluble endoglin.Results14 patients (10 heterozygous FH patients (HeFH), 4 homozygous FH patients (HoFH)) were treated by long-term lipoprotein apheresis. Lipid levels were examined, and ELISA detected biomarkers of inflammation and soluble endoglin. Paired tests were used for intergroup comparisons, and a linear regression model served to estimate the influence of the number of days patients were treated with LA on the studied parameters. LA treatment was associated with a significant decrease of total cholesterol (TC), LDL-C, HDL-C, and apoB, in both HeFH and HoFH patients, after single apheresis and in a long-term period during the monitored interval of 15 years. Biomarkers of inflammation and endothelial dysfunction were reduced for soluble endoglin, hsCRP, and MCP-1, and sP-selectin after each procedure in some HeFH and HoFH patients.ConclusionsLA treatment up to 15 years, reduced cholesterol levels, levels of biomarkers related to endothelial dysfunction, and inflammation not only after each procedure but also in the long-term evaluation in FH patients. We propose that long-term LA treatment improves lipid profile and endothelial dysfunction in familial hypercholesterolemia patients, suggesting a promising improvement in cardiovascular prognosis in most FH patients.
Differences between primary peritoneal serous carcinoma and advanced serous ovarian carcinoma: a study based on the SEER database
Authors: Li Xiaoduo , Yang Qiao , Chen Mingjing , Yang Changqing , Gu Jianfen , Dong Qiang , Yang Guangrong 
Published: February 2021

Abstract
Objective
This study aimed to compare clinical features and overall survival (OS) between patients with primary peritoneal serous carcinoma (PPSC) and those with advanced serous ovarian carcinoma (ASOC) and to identify prognostic factors.

Methods
Patients diagnosed with PPSC and ASOC from 2010 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. Pearson’s chi-square test was used to compare clinical features. The primary endpoint was OS. The Kaplan–Meier method and log–rank test were used to perform the survival analysis. Propensity score matching was also conducted. Univariate, multivariate and subgroup analyses were performed using the Cox proportional hazards model.

Results
A total of 708 PPSC patients and 7610 ASOC patients were enrolled. The clinical features of PPSC patients were noticeably different from those of ASOC patients. The survival analysis showed that PPSC patients had poorer outcomes than ASOC patients. Even after the clinical features were balanced, PPSC patients still had poorer survival. Univariate and multivariate analyses indicated that older age, higher tumor grade and advanced American Joint Committee on Cancer stage were adverse prognostic factors in both groups, while surgery and chemotherapy were protective factors. A subgroup analysis demonstrated that most factors favored ASOC patients. The total distant metastasis rates of PPSC and ASOC were similar. Liver or lung metastasis was common, but bone and brain metastases were rare. A higher proportion of liver metastasis was observed in the ASOC group.

Conclusion
The clinical features and survival outcomes between PPSC patients and ASOC patients are clearly different, and PPSC is more aggressive than ASOC.
Breastfeeding and COVID-19 vaccination: position statement of the Italian scientific societies
Authors: Davanzo Riccardo , Agosti Massimo , Cetin Irene , Chiantera Antonio , Corsello Giovanni , Ramenghi Luca A. , Staiano Annamaria , Tavio Marcello , Villani Alberto , Viora Elsa , Mosca Fabio 
Published: February 2021

AbstractThe availability of a COVID-19 vaccine has raised the issue of its compatibility with breastfeeding. Consequently, the Italian Society of Neonatology (SIN), the Italian Society of Pediatrics (SIP), the Italian Society of Perinatal Medicine (SIMP), the Italian Society of Obstetrics and Gynecology (SIGO), the Italian Association of Hospital Obstetricians-Gynecologists (AOGOI) and the Italian Society of Infectious and Tropical Diseases (SIMIT) have made an ad hoc consensus statement. Currently, knowledge regarding the administration of COVID-19 vaccine to the breastfeeding mother is limited. Nevertheless, as health benefits of breastfeeding are well demonstrated and since biological plausibility suggests that the health risk for the nursed infant is unlikely, Italian scientific societies conclude that COVID-19 vaccination is compatible with breastfeeding.
New genotype invasion of dengue virus serotype 1 drove massive outbreak in Guangzhou, China
Authors: Ma Mengmeng , Wu Sean , He Zhenjian , Yuan Lihong , Bai Zhijun , Jiang Liyun , Marshall John , Lu Jiahai , Yang Zhicong , Jing Qinlong 
Published: February 2021

Abstract
Background
Dengue fever is a mosquito-borne infectious disease that has caused major health problems. Variations in dengue virus (DENV) genes are important features of epidemic outbreaks. However, the associations of DENV genes with epidemic potential have not been extensively examined. Here, we assessed new genotype invasion of DENV-1 isolated from Guangzhou in China to evaluate associations with epidemic outbreaks.

Methodology/principal findings
We used DENV-1 strains isolated from sera of dengue cases from 2002 to 2016 in Guangzhou for complete genome sequencing. A neighbor-joining phylogenetic tree was constructed to elucidate the genotype characteristics and determine if new genotype invasion was correlated with major outbreaks. In our study, a new genotype invasion event was observed during each significant outbreak period in 2002–2003, 2006–2007, and 2013–2014. Genotype II was the main epidemic genotype in 2003 and before. Invasion of genotype I in 2006 caused an unusual outbreak with 765 cases (relative risk [RR] = 16.24, 95% confidence interval [CI] 12.41–21.25). At the middle and late stages of the 2013 outbreak, genotype III was introduced to Guangzhou as a new genotype invasion responsible for 37,340 cases with RR 541.73 (95% CI 417.78–702.45), after which genotypes I and III began co-circulating. Base mutations occurred after new genotype invasion, and the gene sequence of NS3 protein had the lowest average similarity ratio (99.82%), followed by the gene sequence of E protein (99.86%), as compared to the 2013 strain.

Conclusions/significance
Genotype replacement and co-circulation of multiple DENV-1 genotypes were observed. New genotype invasion was highly correlated with local unusual outbreaks. In addition to DENV-1 genotype I in the unprecedented outbreak in 2014, new genotype invasion by DENV-1 genotype III occurred in Guangzhou.

Graphical Abstract
Standard exercise stress testing attenuates peripheral microvascular function in patients with suspected coronary microvascular dysfunction
Authors: Nardone Massimo , Miner Steven , McCarthy Mary , Edgell Heather 
Published: February 2021

Abstract
Background
The effect of exercise on the microvasculature of patients with suspected coronary microvascular dysfunction (CMD), assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT; EndoPAT), is unknown. The present study aimed to determine if standard clinical exercise stress testing (GXT) affected peripheral microvascular function, as determined by the reactive hyperemia index (RHI and LnRHI), in patients with suspected CMD.

Methods
In a cross-sectional study, patients (n = 76) were grouped based on whether the GXT was performed; 1) prior to (exercisers; n = 30), or 2) after the vascular assessment (non-exercisers; n = 46). Patients with an adenosine index of microvascular resistance > 25, adenosine coronary flow reserve (CFR) < 2.0, and/or acetylcholine CFR < 1.5 were considered to have CMD (n = 42). RHI and LnRHI quantified finger pulse amplitude hyperemia following 5 min of forearm ischemia.

Results
LnRHI was lower in patients with CMD compared to patients without CMD, while LnRHI was also lower in exercisers compared to non-exercisers (LnRHI: CMD Non-Exercisers: 0.63 ± 0.25; CMD Exercisers: 0.54 ± 0.19; No CMD Non-Exercisers: 0.85 ± 0.23; No CMD Exercisers: 0.63 ± 0.26; Condition and Exercise Main Effects: Both P < 0.01). In patients who did not exercise prior to the vascular assessment, the receiver operating characteristic curve (ROC) for LnRHI to predict CMD was 0.76 (95% CI: 0.62–0.91; P < 0.01). However, in patients who performed exercise prior to the vascular assessment, the ROC for LnRHI to predict CMD was 0.60 (95% CI: 0.40–0.81; P = 0.34).

Conclusions
CMD is associated with impaired peripheral microvascular function and preceding acute exercise is associated with further reductions of LnRHI. Further, acute exercise abolished the capacity for RH-PAT to predict the presence of CMD in patients with chest pain and non-obstructive coronary arteries. RH-PAT measurements in patients with suspected CMD should not be conducted after exercise has been performed.
Blood transcriptome analysis of patients with uncomplicated bacterial infection and sepsis
Authors: Herwanto Velma , Tang Benjamin , Wang Ya , Shojaei Maryam , Nalos Marek , Shetty Amith , Lai Kevin , McLean Anthony S. , Schughart Klaus 
Published: February 2021

AbstractObjectivesHospitalized patients who presented within the last 24 h with a bacterial infection were recruited. Participants were assigned into sepsis and uncomplicated infection groups. In addition, healthy volunteers were recruited as controls. RNA was prepared from whole blood, depleted from beta-globin mRNA and sequenced. This dataset represents a highly valuable resource to better understand the biology of sepsis and to identify biomarkers for severe sepsis in humans.Data descriptionThe data presented here consists of raw and processed transcriptome data obtained by next generation RNA sequencing from 105 peripheral blood samples from patients with uncomplicated infections, patients who developed sepsis, septic shock patients, and healthy controls. It is provided as raw sequenced reads and as normalized log2transformed relative expression levels. This data will allow performing detailed analyses of gene expression changes between uncomplicated infections and sepsis patients, such as identification of differentially expressed genes, co-regulated modules as well as pathway activation studies.
Pilot study on the effects of preservatives on corneal collagen parameters measured by small angle X-ray scattering analysis
Authors: Kelly Susyn Joan , duPlessis Lizette , Soley John , Noble Frazer , Wells Hannah Carolyn , Kelly Patrick John 
Published: February 2021

Abstract
Objective
Small angle X-ray scattering (SAXS) analysis is a sensitive way of determining the ultrastructure of collagen in tissues. Little is known about how parameters measured by SAXS are affected by preservatives commonly used to prevent autolysis. We determined the effects of formalin, glutaraldehyde, Triton X and saline on measurements of fibril diameter, fibril diameter distribution, and D-spacing of corneal collagen using SAXS analysis.

Results
Compared to sections of sheep and cats’ corneas stored frozen as controls, those preserved in 5% glutaraldehyde and 10% formalin had significantly larger mean collagen fibril diameters, increased fibril diameter distribution and decreased D-spacing. Sections of corneas preserved in Triton X had significantly increased collagen fibril diameters and decreased fibril diameter distribution. Those preserved in 0.9% saline had significantly increased mean collagen fibril diameters and decreased diameter distributions. Subjectively, the corneas preserved in 5% glutaraldehyde and 10% formalin maintained their transparency but those in Triton X and 0.9% saline became opaque. Subjective morphological assessment of transmission electron microscope images of corneas supported the SAXS data. Workers using SAXS analysis to characterize collagen should be alerted to changes that can be introduced by common preservatives in which their samples may have been stored.
A novel fiber-2-edited live attenuated vaccine candidate against the highly pathogenic serotype 4 fowl adenovirus
Authors: Xie Quan , Cao Shiya , Zhang Wei , Wang Weikang , Li Luyuan , Kan Qiuqi , Fu Hui , Geng Tuoyu , Li Tuofan , Wan Zhimin , Gao Wei , Shao Hongxia , Qin Aijian , Ye Jianqiang 
Published: February 2021

AbstractRecently, the outbreaks of hydropericardium-hepatitis syndrome (HHS) caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4) have resulted in huge economic losses to the poultry industry globally. Although several inactivated or subunit vaccines have been developed against FAdV-4, live-attenuated vaccines for FAdV-4 are rarely reported. In this study, a recombinant virus FA4-EGFP expressing EGFP-Fiber-2 fusion protein was generated by the CRISPR/Cas9 technique. Although FA4-EGFP shows slightly lower replication ability than the wild type (WT) FAdV-4, FA4-EGFP was significantly attenuated in vivo compared with the WT FAdV-4. Chickens infected with FA4-EGFP did not show any clinical signs, and all survived to 14 day post-infection (dpi), whereas those infected with FAdV-4 showed severe clinical signs with HHS and all died at 4 dpi. Besides, the inoculation of FA4-EGFP in chickens provided efficient protection against lethal challenge with FAdV-4. Compared with an inactivated vaccine, FA4-EGFP induced neutralizing antibodies with higher titers earlier. All these data not only provide a live-attenuated vaccine candidate against the highly pathogenic FAdV-4 but also give a potential insertion site for developing FAdV-4-based vaccine vectors for delivering foreign antigens.