bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovary-derived circular RNAs profile analysis during the onset of puberty in gilts
Authors: Pan Xiangchun , Gong Wentao , He Yingting , Li Nian , Zhang Hao , Zhang Zhe , Li Jiaqi , Yuan Xiaolong 
Published: June 2021

AbstractBackgroundIn mammals, the ovary is the essential system of female reproduction for the onset of puberty, and the abnormal puberty has negative outcomes on health. CircRNA is a non-coding RNA produced by non-canonical alternative splicing (AS). Several studies have reported that circRNA is involved in the gene regulation and plays an important role in some human diseases. However, the contribution of circRNA has received little known within the onset of puberty in ovary.ResultsHere, the profiles of ovarian circRNAs across pre-, in- and post-pubertal stages were established by RNA-sEq. In total, 972 circRNAs were identified, including 631 stage-specific circRNAs and 8 tissue-specific circRNAs. The biological functions of parental genes of circRNAs were enriched in steroid biosynthesis, autophagy-animal, MAPK signaling pathway, progesterone-mediated oocyte maturation and ras signaling pathway. Moreover, 5 circRNAs derived from 4 puberty-related genes (ESR1, JAK2, NF1 and ARNT) were found in this study. The A3SS events were the most alternative splicing, but IR events were likely to be arose in post-pubertal ovaries. Besides, the circRNA-miRNA-gene networks were explored for 10 differentially expressed circRNAs. Furthermore, the head-to-tail exon as well as the expressions of 10 circRNAs were validated by the divergent RT-qPCR and sanger sequencing.ConclusionsIn summary, the profiles of ovarian circRNAs were provided during pubertal transition in gilts, and these results provided useful information for the investigation on the onset of puberty at the ovarian-circRNAs-level in mammals.
Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK2140944)
Authors: Nuzzo Andrea , Van Horn Stephanie , Traini Christopher , Perry Caroline R. , Dumont Etienne F. , Scangarella-Oman Nicole E. , Gardiner David F. , Brown James R. 
Published: June 2021

Abstract
Background
With increasing concerns about the impact of frequent antibiotic usage on the human microbiome, it is important to characterize the potential for such effects in early antibiotic drug development clinical trials. In a randomised Phase 2a clinical trial study that evaluated the pharmacokinetics of repeated oral doses of gepotidacin, a first-in-chemical-class triazaacenaphthylene antibiotic with a distinct mechanism of action, in adult females with uncomplicated urinary tract infections for gepotidacin (GSK2140944) we evaluated the potential changes in microbiome composition across multiple time points and body-sites (ClinicalTrials.gov: NCT03568942).

Results
Samples of gastrointestinal tract (GIT), pharyngeal cavity and vaginal microbiota were collected with consent from 22 patients at three time points relative to the gepotidacin dosing regimen; Day 1 (pre-dose), Day 5 (end of dosing) and Follow-up (Day 28 ± 3 days). Microbiota composition was determined by DNA sequencing of 16S rRNA gene variable region 4 amplicons. By Day 5, significant changes were observed in the microbiome diversity relative to pre-dose across the tested body-sites. However, by the Follow-up visit, microbiome diversity changes were reverted to compositions comparable to Day 1. The greatest range of microbiome changes by body-site were GIT followed by the pharyngeal cavity then vagina. In Follow-up visit samples we found no statistically significant occurrences of pathogenic taxa.

Conclusion
Our findings suggest that gepotidacin alteration of the human microbiome after 5 days of dosing is temporary and rebound to pre-dosing states is evident within the first month post-treatment. We recommend that future antibiotic drug trials include similar exploratory investigations into the duration and context of microbiome modification and recovery.

Trial registration
NCT03568942. Registered 26 June 2018.
Exploration and validation of hub genes and pathways in the progression of hypoplastic left heart syndrome via weighted gene co-expression network analysis
Authors: Liu Xuelan , Shang Honglei , Li Bin , Zhao Liyun , Hua Ying , Wu Kaiyuan , Hu Manman , Fan Taibing 
Published: June 2021

AbstractBackgroundDespite significant progress in surgical treatment of hypoplastic left heart syndrome (HLHS), its mortality and morbidity are still high. Little is known about the molecular abnormalities of the syndrome. In this study, we aimed to probe into hub genes and key pathways in the progression of the syndrome.MethodsDifferentially expressed genes (DEGs) were identified in left ventricle (LV) or right ventricle (RV) tissues between HLHS and controls using the GSE77798 dataset. Then, weighted gene co-expression network analysis (WGCNA) was performed and key modules were constructed for HLHS. Based on the genes in the key modules, protein–protein interaction networks were conducted, and hub genes and key pathways were screened. Finally, the GSE23959 dataset was used to validate hub genes between HLHS and controls.ResultsWe identified 88 and 41 DEGs in LV and RV tissues between HLHS and controls, respectively. DEGs in LV tissues of HLHS were distinctly involved in heart development, apoptotic signaling pathway and ECM receptor interaction. DEGs in RV tissues of HLHS were mainly enriched in BMP signaling pathway, regulation of cell development and regulation of blood pressure. A total of 16 co-expression network were constructed. Among them, black module (r = 0.79 andpvalue = 2e−04) and pink module (r = 0.84 andpvalue = 4e−05) had the most significant correlation with HLHS, indicating that the two modules could be the most relevant for HLHS progression. We identified five hub genes in the black module (includingFbn1,Itga8,Itga11,Itgb5andThbs2), and five hub genes (includingCblb,Ccl2,Edn1,Itgb3andMap2k1) in the pink module for HLHS. Their abnormal expression was verified in the GSE23959 dataset.ConclusionsOur findings revealed hub genes and key pathways for HLHS through WGCNA, which could play key roles in the molecular mechanism of HLHS.
Characteristics of coronary artery disease in patients with subclinical hypothyroidism: evaluation using coronary artery computed tomography angiography
Authors: Zhou Xin-zhu , Shi Rui , Wang Jin , Shi Ke , Liu Xi , Li Yuan , Gao Yue , Guo Ying-kun , Yang Zhi-gang 
Published: June 2021

Abstract
Background
Subclinical hypothyroidism (SCH) has recently been acknowledged as an independent risk factor for coronary artery disease (CAD). However, the characteristics of CAD in patients with SCH are not fully understood. This study aims to evaluate the features of CAD in patients with SCH using coronary computed tomographic angiography (CCTA).

Materials and methods
From 1 April, 2018 to 30 June, 2020, 234 consecutive SCH patients with coronary plaques identified on CCTA were included retrospectively. They were further subdivided into different degree of SCH groups (mild SCH vs. moderate SCH vs. severe SCH: 143 vs 62 vs 28) and different gender groups (men with SCH vs. women with SCH:116 vs 118). The distributions and types of plaques, luminal narrowing, segment involvement scores (SIS) and segment stenosis scores (SSS) were evaluated and compared among the different groups.

Results
Patients with severe SCH had fewer calcified plaques (0.7 ± 0.9 vs. 2.0 ± 1.9, p < 0.001) and more non-calcified plaques (0.9 ± 1.0 vs. 0.3 ± 0.5, p < 0.001) than those with mild SCH. As the SCH condition worsened, the proportion of non-calcified plaques significantly increased. Whereas there were no significant discrepancies in SIS and SSS among patients with different grades of SCH (all p > 0.05). Men with SCH had higher SIS (3.9 ± 2.3 vs. 3.0 ± 2.3, p = 0.004) and SSS (7.8 ± 5.4 vs. 5.4 ± 3.0, p = 0.002) than women. Multivariate logistic and linear regression analysis demonstrated that grades of SCH (Moderate SCH, odds ratio [OR] 2.11; 95% CI 1.03–4.34, p = 0.042; severe SCH, OR: 10.00; 95% CI 3.82–26.20, p < 0.001, taken mild SCH as a reference) was independently associated with the presence of non-calcified plaques, whereas sex (B: 1.67; 95% CI 0.27–3.10, p = 0.009) was independently associated with SSS.

Conclusions
Severe SCH is associated with non-calcified plaques, and men with SCH have higher total plaque burden than women. We suggest that it is important to evaluate for coronary plaque in SCH patients, especially those with severe SCH and men with SCH.
Integrated analysis of the functions and prognostic values of RNA binding proteins in hepatocellular carcinoma
Authors: Wu Zeng-Hong , Huang Hong-Ming , Yang Dong-Liang 
Published: June 2021

Abstract
Background
Hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide, ranks as the fifth most common cancer and has been the second most frequent cause of cancer-related death. RNA binding proteins (RBPs) are proteins that interact with different classes of RNA and are commonly detected in cells.

Methods
We used RNA sequencing data from TCGA to display dysfunctional RBPs microenvironments and provide potential useful biomarkers for HCC diagnosis and prognosis.

Results
330 differently expressed RBPs (208 upregulated and 122 downregulated) were identified. KEGG were mainly enriched in RNA degradation, Influenza A, Hepatitis C, RIG-I-like receptor signaling pathway, Herpes simplex virus 1 infection and RNA transport. CBioPortal results demonstrated that these genes were altered in 50 samples out of 357 HCC patients (14%) and the amplification of BRCA1 was the largest frequent copy-number alteration.

Conclusion
Based on the online database, we identified novel RBPs markers for the prognosis of hepatocellular carcinoma.
Factors associated with eating performance in older adults with dementia in long-term care facilities: a cross-sectional study
Authors: Jung Dukyoo , De Gagne Jennie C. , Lee Hyesoon , Lee Minkyung 
Published: June 2021

Abstract
Background
The purpose of this study was to investigate factors influencing eating performance in older adults with dementia (OAWDs) in long-term care (LTC) facilities.

Methods
This cross-sectional study examined risk factors for compromised eating performance by comparing both independent and dependent older adults with dementia. The study participants were 117 OAWDs in LTC facilities in South Korea. Measurements included (a) general characteristics, (b) activities of daily living (ADL) including eating performance, (c) cognitive function, (d) physical capability, (e) grip strength, (f) Behavioral Psychological Symptoms of Dementia (BPSD), and (g) depression. Data were analyzed by the percentage, mean and standard deviation, Chi-square test, t-test, and logistic regression.

Results
The eating independent group had more comorbidities than the dependent group (t = 2.793, p < .006); had significantly higher cognition (t = 4.108, p < .001) and physical capability (t = 5.258, p < .001); and had stronger grip strength (t = 2.887, p = .005). Comorbidities and physical capability were determinants for independent eating performance (Odds Ratio [OR] = 1.969, p = .014; OR = 1.324, p < .001).

Conclusions
It is suggested that maintaining physical capability should be encouraged to support independent eating performance by OAWDs in LTC facilities. The results of this study could serve as a basis for developing function-focused care to maintain the residual eating performance of OAWDs in Korean LTC facilities. This is a subject area that has not been fully explored.
Adenosine deaminase negative pleural tuberculosis: a case report
Authors: Boggs Zachary H. , Heysell Scott , Eby Joshua , Arnold Christopher 
Published: June 2021

Abstract
Background
A pleural fluid adenosine deaminase (ADA) has been used globally to assist in the diagnosis of a tuberculous pleural effusion (TPE) with a notable negative predictive value.

Case presentation
We report a case of a patient with a negative pleural fluid ADA who was found to have culture-positive and biopsy-proven Mycobacterium tuberculosis.

Conclusions
This case shows the importance of pursuing gold standard diagnostic studies when clinical suspicion remains high despite negative preliminary testing. We further describe gaps in research to improve pleural fluid biomarkers for TPE.
Protective population behavior change in outbreaks of emerging infectious disease
Authors: Lodge Evans K. , Schatz Annakate M. , Drake John M. 
Published: June 2021

Abstract
Background
During outbreaks of emerging and re-emerging infections, the lack of effective drugs and vaccines increases reliance on non-pharmacologic public health interventions and behavior change to limit human-to-human transmission. Interventions that increase the speed with which infected individuals remove themselves from the susceptible population are paramount, particularly isolation and hospitalization. Ebola virus disease (EVD), Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS) are zoonotic viruses that have caused significant recent outbreaks with sustained human-to-human transmission.

Methods
This investigation quantified changing mean removal rates (MRR) and days from symptom onset to hospitalization (DSOH) of infected individuals from the population in seven different outbreaks of EVD, SARS, and MERS, to test for statistically significant differences in these metrics between outbreaks.

Results
We found that epidemic week and viral serial interval were correlated with the speed with which populations developed and maintained health behaviors in each outbreak.

Conclusions
These findings highlight intrinsic population-level changes in isolation rates in multiple epidemics of three zoonotic infections with established human-to-human transmission and significant morbidity and mortality. These data are particularly useful for disease modelers seeking to forecast the spread of emerging pathogens.
Effect of increased blood flow rate on renal anemia and hepcidin concentration in hemodialysis patients
Authors: Yamamoto Masateru , Matsumoto Tomio , Ohmori Hiromitsu , Takemoto Masahiko , Ikeda Masanobu , Sumimoto Ryo , Kobayashi Tsuyoshi , Kato Akihiko , Ohdan Hideki 
Published: June 2021

Abstract
Background
Increasing the blood flow rate (BFR) is a useful method for increasing Kt/V and the clearance for low molecular solutes. Hemodialysis patients are often anemic due to hypoerythropoiesis and their chronic inflammatory state. Hepcidin, a hormone that regulates iron homeostasis, is considered as an indicator of iron deficiency in patients with end-stage renal disease. This study aimed to investigate the effects of an increased BFR during hemodialysis on serum hepcidin levels and anemia.

Methods
Between April 2014 and March 2016, 22 chronic dialysis patients (11 men [50.0 %]; mean [± standard deviation] age, 72 ± 12 years) undergoing maintenance hemodialysis treatment, thrice weekly, were enrolled and followed prospectively for 24 months. In April 2014, the BFR was 200 mL/min; in April 2015 this was increased to 400 mL/min, which was within acceptable limits. The dialysate flow rate remained stable at; 500mlL/min. Blood samples were collected in March 2015 and 2016. The primary endpoint was the comparison of the amounts of erythropoiesis-stimulating agent (ESA) required.

Results
The increased BFR increased the Kt/V and contributed to significantly decreased urea nitrogen (UN) (p = 0.015) and creatinine (Cr) (p = 0.005) levels. The dialysis efficiency was improved by increasing the BFR. Ferritin (p = 0.038), hepcidin (p = 0.041) and high-sensitivity interleukin-6 (p = 0.038) levels were also significantly reduced. The ESA administered was significantly reduced (p = 0.004) and the Erythropoietin Resistant Index (ERI) significantly improved (p = 0.031). The reduction rates in UN (p < 0.001), Cr (p < 0.001), and beta-2 microglobulin (p = 0.017) levels were significantly greater post the BFR increase compared to those prior to the BFR increase. However, hepcidin was not affected by the BFR change.

Conclusions
Increasing BFR was associated with hemodialysis efficiency, and led to reduce inflammatory cytokine interleukin-6, but did not contribute to reduce C-reactive protein. This reduced hepcidin levels, ESA dosage and ERI. Hepcidin levels were significantly correlated with ferritin levels, and it remains to be seen whether reducing hepcidin leads to improve ESA and iron availability during anemia management.
Co-occurrence of thyroid and breast cancer is associated with an increased oncogenic SNP burden
Authors: Bakos Bence , Kiss András , Árvai Kristóf , Szili Balázs , Deák-Kocsis Barbara , Tobiás Bálint , Putz Zsuzsanna , Ármós Richárd , Balla Bernadett , Kósa János , Dank Magdolna , Valkusz Zsuzsanna , Takács István , Tabák Ádám , Lakatos Péter 
Published: June 2021

Abstract
Background
Epidemiological evidence suggests that synchronous or metachronous presentation of breast and thyroid cancers exceeds that predicted by chance alone. The following potential explanations have been hypothesized: common environmental or hormonal factors, oncogenic effect of the treatment for the first cancer, closer follow-up of cancer survivors, shared underlying genetic risk factors. While some cases were found to be related to monogenic disorders with autosomal inheritance, the genetic background of most cases of co-occurring breast and thyroid cancer is thought to be polygenic.

Methods
In this retrospective case-control study we compared the genetic profile of patients with a history of breast cancer (n = 15) to patients with co-occurring breast and thyroid cancer (n = 19) using next generation sequencing of 112 hereditary cancer risk genes. Identified variants were categorized based on their known association with breast cancer and oncogenesis in general.

Results
No difference between patients with breast and double cancers was observed in clinical and pathological characteristics or the number of neutral SNPs. The unweighted and weighted number of SNPs with an established or potential association with breast cancer was significantly lower in the group with breast cancer only (mean difference − 0.58, BCa 95% CI [− 1.09, − 0.06], p = 0.029, and mean difference − 0.36, BCa 95% CI [− 0.70, − 0.02], p = 0.039, respectively). The difference was also significant when we compared the number of SNPs with potential or known association with any malignancy (mean difference − 1.19, BCa 95% CI [− 2.27, − 0.11], p = 0.032 for unweighted, and mean difference − 0.73, BCa 95% CI [− 1.32, − 0.14], p = 0.017 for weighted scores).

Conclusion
Our findings are compatible with the hypothesis of genetic predisposition in the co-occurrence of breast and thyroid cancer. Further exploration of the underlying genetic mechanisms may help in the identification of patients with an elevated risk for a second cancer at the diagnosis of the first cancer.
Efficacy of adjuvant chemotherapy stratified by age and the 21-gene recurrence score in estrogen receptor-positive breast cancer
Authors: Yu Jing , Lin Caijin , Huang Jiahui , Hong Jin , Gao Weiqi , Zhu Siji , Lin Lin , Chen Xiaosong , Huang Ou , He Jianrong , Zhu Li , Chen Weiguo , Li Yafen , Wu Jiayi , Shen Kunwei 
Published: June 2021

AbstractBackgroundThe 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2-) early breast cancer patients. Age would influence the interaction between RS and chemotherapy effect. The current study aimed to determine RS thresholds which were predictive of chemotherapy benefit in young and old women, respectively.MethodsPatients diagnosed with pN0–1, ER+/HER2- breast cancer between 2009 and 2016 were retrospectively reviewed. Propensity score matching was performed according to chemotherapy usage. After stratifying patients with different cutoffs of age, the RS threshold indicating chemotherapy benefit in each age strata were determined by cox proportional hazard models.ResultsA total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS thresholds suggesting chemotherapy benefit varied with age. For patients ≤55 years, chemotherapy benefit was observed in those having RS > 25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) of 97.0 and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS: 95.3% vs. 94.6%). For patients > 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS > 36 (P = 0.014, 4-year IDFS: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS: 92.3% vs. 95.8%).ConclusionsOld patients need higher RS thresholds to demonstrate the chemotherapy benefit. Further efforts are warranted to investigate the association between age and predictive RS thresholds.
Predictive factors for survival following stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumour thrombosis and construction of a nomogram
Authors: Li Xiaojie , Ye Zhimin , Lin Sheng , Pang Haowen 
Published: June 2021

Abstract
Background
We evaluated the treatment response and predictive factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT), who underwent stereotactic body radiotherapy (SBRT). Additionally, we developed and validated a personalised prediction model for patient survival.

Methods
Clinical information was retrospectively collected for 80 patients with HCC and PVTT, who were treated with SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) between December 2015 and June 2019. A multivariate Cox proportional hazard regression model was used to identify the independent predictive factors for survival. Clinical factors were subsequently presented in a nomogram. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the accuracy of the model and the net clinical benefit.

Results
All patients completed the planned radiotherapy treatment, and the median follow-up duration was 10 months (range, 1–35.3 months). The median survival duration was 11.5 months, with 3-, 6-, and 12-month survival rates of 92.5, 74.5, and 47.5%, respectively. The multivariable Cox regression model indicated that the following were significant independent predictors of OS: clinical T stage (p = 0.001, hazard ratio [HR] = 3.085, 95% confidence interval [CI]: 1.514–6.286), cirrhosis (p = 0.014, HR = 2.988, 95% CI: 1.246–7.168), age (p = 0.005, HR = 1.043, 95% CI: 1.013–1.075), alpha-fetoprotein level (p = 0.022, HR = 1.000, 95% CI: 1.000–1.000), and haemoglobin level (p = 0.008, HR = 0.979, 95% CI: 0.963–0.994). A nomogram based on five independent risk factors and DCA demonstrated a favourable predictive accuracy of patient survival (AUC = 0.74, 95% CI: 0.63–0.85) and the clinical usefulness of the model.

Conclusions
SBRT is an effective treatment for patients with HCC with PVTT. Notably, clinical T stage, presence of cirrhosis, age, alpha-fetoprotein levels, and haemoglobin levels are independent prognostic factors for survival. The presented nomogram can be used to predict the survival of patients with HCC and PVTT, who underwent SBRT.