bluuebunny/crossref_metadata_2025_split huggingface dataset:
fcfdr: an R package to leverage continuous and binary functional genomic data in GWAS
Authors: Hutchinson Anna , Liley James , Wallace Chris 
Published: July 2022

AbstractBackgroundGenome-wide association studies (GWAS) are limited in power to detect associations that exceed the stringent genome-wide significance threshold. This limitation can be alleviated by leveraging relevant auxiliary data, such as functional genomic data. Frameworks utilising the conditional false discovery rate have been developed for this purpose, and have been shown to increase power for GWAS discovery whilst controlling the false discovery rate. However, the methods are currently only applicable for continuous auxiliary data and cannot be used to leverage auxiliary data with a binary representation, such as whether SNPs are synonymous or non-synonymous, or whether they reside in regions of the genome with specific activity states.ResultsWe describe an extension to the cFDR framework for binary auxiliary data, called “Binary cFDR”. We demonstrate FDR control of our method using detailed simulations, and show that Binary cFDR performs better than a comparator method in terms of sensitivity and FDR control. We introduce an all-encompassing user-oriented CRAN R package (https://annahutch.github.io/fcfdr/;https://cran.r-project.org/web/packages/fcfdr/index.html) and demonstrate its utility in an application to type 1 diabetes, where we identify additional genetic associations.ConclusionsOur all-encompassing R package, , serves as a comprehensive toolkit to unite GWAS and functional genomic data in order to increase statistical power to detect genetic associations.
Osmoregulatory strategies of estuarine fish Scatophagus argus in response to environmental salinity changes
Authors: Su Maoliang , Liu Nanxi , Zhang Zhengqi , Zhang Junbin 
Published: July 2022

AbstractBackgroundScatophagus argus, an estuarine inhabitant, can rapidly adapt to different salinity environments. However, the knowledge of the molecular mechanisms underlying its strong salinity tolerance remains unclear. The gill, as the main osmoregulatory organ, plays a vital role in the salinity adaptation of the fish, and thus relative studies are constructive to reveal unique osmoregulatory mechanisms inS.argus.ResultsIn the present study, iTRAQ coupled with nanoLC-MS/MS techniques were employed to explore branchial osmoregulatory mechanisms inS. argusacclimated to different salinities. Among 1,604 identified proteins, 796 differentially expressed proteins (DEPs) were detected. To further assess osmoregulatory strategies in the gills under different salinities, DEPs related to osmoregulatory (22), non-directional (18), hypo- (52), and hypersaline (40) stress responses were selected. Functional annotation analysis of these selected DEPs indicated that the cellular ion regulation (e.g. Na+-K+-ATPase [NKA] and Na+-K+-2Cl−cotransporter 1 [NKCC1]) and ATP synthesis were deeply involved in the osmoregulatory process. As an osmoregulatory protein, NKCC1 expression was inhibited under hyposaline stress but showed the opposite trend in hypersaline conditions. The expression levels of NKA α1 and β1 were only increased under hypersaline challenge. However, hyposaline treatments could enhance branchial NKA activity, which was inhibited under hypersaline environments, and correspondingly, reduced ATP content was observed in gill tissues exposed to hyposaline conditions, while its contents were increased in hypersaline groups.In vitroexperiments indicated that Na+, K+, and Cl−ions were pumped out of branchial cells under hypoosmotic stress, whereas they were absorbed into cells under hyperosmotic conditions. Based on our results, we speculated that NKCC1-mediated Na+influx was inhibited, and proper Na+efflux was maintained by improving NKA activity under hyposaline stress, promoting the rapid adaptation of branchial cells to the hyposaline condition. Meanwhile, branchial cells prevented excessive loss of ions by increasing NKA internalization and reducing ATP synthesis. In contrast, excess ions in cells exposed to the hyperosmotic medium were excreted with sufficient energy supply, and reduced NKA activity and enhanced NKCC1-mediated Na+influx were considered a compensatory regulation.ConclusionsS. argusexhibited divergent osmoregulatory strategies in the gills when encountering hypoosmotic and hyperosmotic stresses, facilitating effective adaptabilities to a wide range of environmental salinity fluctuation.
Exogenous melatonin increases salt tolerance in bitter melon by regulating ionic balance, antioxidant system and secondary metabolism-related genes
Authors: Sheikhalipour Morteza , Mohammadi Seyed Abolghasem , Esmaielpour Behrooz , Zareei Elnaz , Kulak Muhittin , Ali Sajid , Nouraein Mojtaba , Bahrami Mohammad Kazem , Gohari Gholamreza , Fotopoulos Vasileios 
Published: July 2022

Abstract
Background
Melatonin is a multi-functional molecule widely employed in order to mitigate abiotic stress factors, in general and salt stress in particular. Even though previous reports revealed that melatonin could exhibit roles in promoting seed germination and protecting plants during various developmental stages of several plant species under salt stress, no reports are available with respect to the regulatory acts of melatonin on the physiological and biochemical status as well as the expression levels of defense- and secondary metabolism-related related transcripts in bitter melon subjected to the salt stress.

Results
Herewith the present study, we performed a comprehensive analysis of the physiological and ion balance, antioxidant system, as well as transcript analysis of defense-related genes (WRKY1, SOS1, PM H+-ATPase, SKOR, Mc5PTase7, and SOAR1) and secondary metabolism-related gene expression (MAP30, α-MMC, polypeptide-P, and PAL) in salt-stressed bitter melon (Momordica charantia L.) plants in response to melatonin treatment. In this regard, different levels of melatonin (0, 75 and 150 µM) were applied to mitigate salinity stress (0, 50 and 100 mM NaCl) in bitter melon. Accordingly, present findings revealed that 100 mM salinity stress decreased growth and photosynthesis parameters (SPAD, Fv/Fo, Y(II)), RWC, and some nutrient elements (K+, Ca2+, and P), while it increased Y(NO), Y(NPQ), proline, Na+, Cl−, H2O2, MDA, antioxidant enzyme activity, and lead to the induction of the examined genes. However, prsiming with 150 µM melatonin increased SPAD, Fv/Fo, Y(II)), RWC, and K+, Ca2+, and P concentration while decreased Y(NO), Y(NPQ), Na+, Cl−, H2O2, and MDA under salt stress. In addition, the antioxidant system and gene expression levels were increased by melatonin (150 µM).

Conclusions
Overall, it can be postulated that the application of melatonin (150 µM) has effective roles in alleviating the adverse impacts of salinity through critical modifications in plant metabolism.
Blunt traumatic right coronary artery dissection presenting with second-degree atrioventricular block and late-onset severe cardiogenic shock
Authors: Paparoupa Maria , Conradi Lenard , Warncke Malte Lennart , Well Lennart , Burdelski Christoph , Cramer Christopher , Grahn Hanno , Kubik Mathias , Kluge Stefan 
Published: July 2022

Abstract
Background
Blunt chest injury may induce several cardiovascular traumata, requiring immediate care. Right coronary artery dissection (RCA) is an extremely rare sequela in this setting and is associated with high mortality, if it remains undiagnosed.

Case presentation
We present the case of an RCA dissection after blunt chest trauma in a 16-year-old patient, who initially presented with a second-degree atrioventricular block as solitary manifestation on admission. Typical electrocardiographic findings, such as ST segmental changes or pathological Q waves were absent. Serial echocardiograms excluded segmental motion abnormalities, pericardial effusion or right ventricular strain. Nevertheless, a complementary computed tomography coronary angiography revealed this potentially lethal condition several hours later. The patient underwent an emergency surgical myocardial revascularization under the circulatory support of veno-arterial extracorporeal membrane oxygenation and suffered a prolonged right ventricular insufficiency with severe late-onset cardiogenic shock, due to an extensive myocardial infarction of the inferoseptal ventricular wall.

Conclusion
Right coronary artery dissection after high-speed blunt chest injury constitutes a diagnostic challenge, especially in the absence of typical electrocardiographic and echocardiographic findings in young patients. This condition may dramatically deteriorate in time, leading to severe cardiogenic shock and life-threatening arrhythmias.
An integrative review on individual determinants of enrolment in National Health Insurance Scheme among older adults in Ghana
Authors: Morgan Anthony Kwame , Adei Dina , Agyemang-Duah Williams , Mensah Anthony Acquah 
Published: July 2022

Abstract
Background
We conducted an integrative review in an attempt to methodically and systematically understand the individual (personal factors) that influence National Health Insurance Scheme [NHIS] enrolment among older adults aged 50 years and above. The study was premised on evidence pointing to a state of little or no change in the enrolment rates [especially among older adults], which contrasts with the initial euphoria that greeted the launch of the scheme - which culminated in high enrolment rates.

Methods
The integrative literature review was conducted to synthesise the available evidence on individual determinants of NHIS among older adults. The methodological approach of the integrative literature review follows a five-stage interdependent and interconnected procedure of problem identification, literature search, data evaluation, data analysis and results presentation. Studies that met the inclusion criteria were peer-reviewed articles published in the English Language, from January 2010 to July 2020 and have Ghana as its setting or study area. The Andersen's Behavioural Model was used to categorize the predictor variables.

Results
Predisposing factors [gender, age, level of education and marital status], enabling factors [income] and need factors [health conditions or health attributes of older adults] were identified as individual predictors of NHIS enrolment among older adults. The findings support argument of Andersen's Behavioural Model [where predisposing, enabling and need factors are considered as individual determinants of health behaviour].

Conclusions
The findings call for policy reforms that take into account the aforementioned individual predictors of NHIS enrolment, especially among the aged.
The prevalence of alcoholic and nonalcoholic fatty liver disease in adolescents and young adults in the United States: analysis of the NHANES database
Authors: Alkhouri Naim , Almomani Ashraf , Le Phuc , Payne Julia Y. , Asaad Imad , Sakkal Celine , Vos Miriam , Noureddin Mazen , Kumar Prabhat 
Published: July 2022

Abstract
Background
The prevalence of fatty liver disease is potentially increasing in adolescents and young adults (AYAs) due to the obesity and alcohol pandemics. The aim of this study was to assess the prevalence of alcohol-associated fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) in a representative U.S. cohort utilizing transient elastography to directly measure hepatic steatosis and suspected fibrosis.

Methods
AYAs (age 15–39 years) with valid FibroScan® measurements in the National Health and Nutrition Examination Survey (NHANES) database (2017–2018) were included in the analyses. Those with viral hepatitis, pregnancy, or ALT/AST > 500 U/L were excluded. The population was divided into those with excessive alcohol consumption (ALQ130) and those without. Controlled attenuation parameter (CAP) score ≥ 248 dB/m was used to identify suspected ALD and NAFLD. In those with evidence of ALD, the following cutoffs of liver stiffness measurement (LSM) were used for suspected fibrosis: F ≥ F2 at LSM ≥ 7.5 kPa and F ≥ F3 at ≥ 9.5 kPa, respectively. In those with suspected NAFLD, the following LSM cutoffs were used: F ≥ F2 at 6.1 and F ≥ F3 at ≥ 7.1, respectively. Cutoffs were chosen based on published literature to maximize sensitivity.

Results
Comparing to those without, subjects with excessive alcohol consumption tended to be older (29.8 vs 28.5 years), have a higher BMI (29.3 vs 28.9 kg/m2), and be from a White ethnicity (65.3% vs. 55.4%). In subjects with excessive alcohol consumption, suspected ALD was present in 56.59% (95% CI 41.57–70.49). In those with suspected ALD, suspected significant fibrosis (F ≥ F2) was present in 12.3% (95% CI 4.74–28.34) and advanced fibrosis (F ≥ F3) was present in 6.31% (95% CI 0.69–39.55). Similarly, in subjects without excessive alcohol consumption, suspected NAFLD was present in 40.04% (36.64–43.54). In those with suspected NAFLD, suspected significant fibrosis (F ≥ F2) was present in 31.07% (27.25–35.16) and suspected advanced fibrosis (F ≥ F3) was present in 20.15% (16.05–24.99).

Conclusion
A significant percentage of AYAs are at risk for ALD and NAFLD and a subset of these subjects is at risk for significant fibrosis. Efforts should focus on increasing awareness of the prevalence of ALD and NAFLD in this population and to mitigate modifiable risk factors.
Clinical efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in treatment of cesarean scar pregnancy (CSP) I and II
Authors: Liu Yanglu , Yin Qiaozhi , Xu Fan , Luo Shuang 
Published: July 2022

Abstract
Objective
To investigate the safety and feasibility of high intensity focused ultrasound (HIFU) ablation followed by ultrasound-guided dilation and curettage (USg-D&C) for two types patients with cesarean scar pregnancy (CSP-I and CSP-II).

Materials and methods
This study was a retrospective analysis of 101 CSP-I patients and 52 CSP-II patients who received HIFU ablation followed by USg-D&C from Jun 2014 to Oct 2020. The diameter of gestational sac/mass, thickness of the intervening myometrium, intraoperative blood loss, operation time, length of hospital stays, adverse effects and β-HCG level in the two groups were compared.

Results
All patients successfully received HIFU ablation under conscious sedation. The median total treatment time of HIFU ablation and median USg-D&C time in the CSP-I group were statistically longer than those in the CSP-II group (P < 0.05). The average intraoperative median blood loss was 39 ml in the CSP-I group and 65 ml in the CSP-II group (P < 0.05). The duration of hospitalization was 7.07 ± 1.83 days in the CSP-I group and 7.18 ± 1.72 days in the CSP-II group (P > 0.05). The average time needed for β-HCG return to normal levels was 26.08 ± 5.02. and 28.15 ± 4.99 days for CSP-I and CSP-II, respectively (P > 0.05). The percentage of adverse effects and complications was not significantly different between the two groups (P > 0.05).

Conclusions
HIFU ablation followed by USg-D&C was safe and effective in treating the CSP-I patients and CSP-II patients, which may be a potential noninvasive therapeutic option for patients with CSP.
HE4 as a serum biomarker for the diagnosis of pelvic masses: a prospective, multicenter study in 965 patients
Authors: Braicu Elena Ioana , Krause Catherine Linn , Torsten Uwe , Mecke Herbert , Richter Rolf , Hellmeyer Lars , Lanowska Malgorzata , Müller Bodo , Koch Elisa , Boenneß-Zaloum Janine , Ames Kerstin , Chekerov Radoslav , Hasenbein Kati , Zimmermann Mathias , Mangler Mandy , Chen Frank , Tauber Rudolf , Sehouli Jalid 
Published: July 2022

Abstract
Background
To evaluate the diagnostic value of adding human epididymis protein 4 (HE4), cancer antigen 125 (CA125) and risk of malignancy algorithm (ROMA) to ultrasound for detecting ovarian cancer in patients with a pelvic mass.

Methods
This was a prospective, observational, multicenter study. Patients aged > 18 years who were scheduled to undergo surgery for a suspicious pelvic mass had CA125 and HE4 levels measured prior to surgery, in addition to a routine transvaginal ultrasound scan. The diagnostic performance of CA125, HE4 and ROMA for distinguishing between benign and malignant adnexal masses was assessed using receiver operating characteristic (ROC) analysis and the corresponding area under the curve (AUC).

Results
Of 965 evaluable patients, 804 were diagnosed with benign tumors and 161 were diagnosed with ovarian cancer. In late-stage ovarian cancer, CA125, HE4 and ROMA all had an excellent diagnostic performance (AUC > 0.92), whereas in stage I and II, diagnostic performance of all three biomarkers was less adequate (AUC < 0.77). In the differential diagnosis of ovarian cancer and endometriosis, ROMA and HE4 performed better than CA125 with 99 and 98.1% versus 75.0% sensitivity, respectively, at 75.4% specificity.

Conclusions
ROMA and HE4 could be valuable biomarkers to help with the diagnosis of ovarian cancer in premenopausal patients in order to differentiate from endometriosis, whereas CA125 may be more adequate for postmenopausal patients.
An integrative transcriptome analysis reveals potential predictive, prognostic biomarkers and therapeutic targets in colorectal cancer
Authors: Samadi Pouria , Soleimani Meysam , Nouri Fatemeh , Rahbarizadeh Fatemeh , Najafi Rezvan , Jalali Akram 
Published: July 2022

AbstractBackgroundA deep understanding of potential molecular biomarkers and therapeutic targets related to the progression of colorectal cancer (CRC) from early stages to metastasis remain mostly undone. Moreover, the regulation and crosstalk among different cancer-driving molecules including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs) in the transition from stage I to stage IV remain to be clarified, which is the aim of this study.MethodsWe carried out two separate differential expression analyses for two different sets of samples (stage-specific samples and tumor/normal samples). Then, by the means of robust dataset analysis we identified distinct lists of differently expressed genes (DEGs) for Robust Rank Aggregation (RRA) and weighted gene co-expression network analysis (WGCNA). Then, comprehensive computational systems biology analyses including mRNA-miRNA-lncRNA regulatory network, survival analysis and machine learning algorithms were also employed to achieve the aim of this study. Finally, we used clinical samples to carry out validation of a potential and novel target in CRC.ResultsWe have identified the most significant stage-specific DEGs by combining distinct results from RRA and WGCNA. After finding stage-specific DEGs, a total number of 37 DEGs were identified to be conserved across all stages of CRC (conserved DEGs). We also found DE-miRNAs and DE-lncRNAs highly associated to these conserved DEGs. Our systems biology approach led to the identification of several potential therapeutic targets, predictive and prognostic biomarkers, of which lncRNA LINC00974 shown as an important and novel biomarker.ConclusionsFindings of the present study provide new insight into CRC pathogenesis across all stages, and suggests future assessment of the functional role of lncRNA LINC00974 in the development of CRC.
Four-gene signature predicting overall survival and immune infiltration in hepatocellular carcinoma by bioinformatics analysis with RT‒qPCR validation
Authors: Guan Renguo , Zou Jingwen , Mei Jie , Deng Min , Guo Rongping 
Published: July 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most lethal cancers, with a poor prognosis. Prognostic biomarkers for HCC patients are urgently needed. We aimed to establish a nomogram prediction system that combines a gene signature to predict HCC prognosis.

Methods
Differentially expressed genes (DEGs) were identified from publicly available Gene Expression Omnibus (GEO) datasets. The Cancer Genome Atlas (TCGA) cohort and International Cancer Genomics Consortium (ICGC) cohort were regarded as the training cohort and testing cohort, respectively. First, univariate and multivariate Cox analyses and least absolute shrinkage and selection operator (LASSO) regression Cox analysis were performed to construct a predictive risk score signature. Furthermore, a nomogram system containing a risk score and other prognostic factors was developed. In addition, a correlation analysis of risk group and immune infiltration was performed. Finally, we validated the expression levels using real-time PCR.

Results
Ninety-five overlapping DEGs were identified from four GEO datasets, and we constructed a four-gene-based risk score predictive model (risk score = EZH2 * 0.075 + FLVCR1 * 0.086 + PTTG1 * 0.015 + TRIP13 * 0.020). Moreover, this signature was an independent prognostic factor. Next, the nomogram system containing risk score, sex and TNM stage indicated better predictive performance than independent prognostic factors alone. Moreover, this signature was significantly associated with immune cells, such as regulatory T cells, resting NK cells and M2 macrophages. Finally, RT‒PCR confirmed that the mRNA expressions of four genes were upregulated in most HCC cell lines.

Conclusion
We developed and validated a nomogram system containing the four-gene risk score, sex, and TNM stage to predict prognosis.
Childhood trauma, posttraumatic stress disorder symptoms, early maladaptive schemas, and schema modes: a comparison of individuals with obesity and normal weight controls
Authors: Spirou Dean , Raman Jayanthi , Bishay Ramy H. , Ahlenstiel Golo , Smith Evelyn 
Published: July 2022

Abstract
Background
Previous research on the psychological mechanisms of obesity has primarily focused on acute psychopathology. However, there is limited literature on the role of more complex and entrenched psychological processes in weight management. The current study aimed to expand previous research by examining more enduring psychological constructs, including early maladaptive schemas (EMS), schemas modes, and trauma.

Methods
Participants (N = 125) comprised adults with normal weight (n = 40) and obesity (n = 85) from community and clinical settings in Australia. Eligible participants completed a series of self-report questionnaires via Research Electronic Data Capture (REDCap). Two, separate, one-way multivariate analysis of variance (MANOVA) were conducted to examine group differences on the outcome variables.

Results
Findings indicated a significant effect of group on EMS and schema modes, V = .51, F(32, 92) = 2.97, p < .001, partial η2 = .51. Follow-up univariate tests revealed that individuals with obesity endorsed significantly more maladaptive schemas and schema modes and significantly less healthy schema modes than individuals with normal weight. In addition, results demonstrated a significant effect of group on childhood trauma and posttraumatic stress disorder (PTSD) symptoms, V = .19, F(6, 118) = 4.70, p < .001, partial η2 = .19. Subsequent univariate tests and chi-square analyses indicated that individuals with obesity reported significantly more childhood trauma as well as significantly more PTSD symptoms within the last month than normal weight individuals.

Conclusion
This was the first study to compare EMS and schema modes in treatment-seeking individuals with obesity and normal weight controls using the short form version 3 of the Young Schema Questionnaire and revised, 118-item, Schema Mode Inventory. Overall, findings revealed that individuals with obesity experience more complex and enduring psychological difficulties than normal weight individuals. Increased assessment and targeted treatment of these underlying mental health concerns may contribute to a more holistic conceptualisation of obesity and could improve the long-term success of weight management.