bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avian corticosteroid-binding globulin: biological function and regulatory mechanisms in physiological stress responses
Authors: Lin Hai-Yan , Song Gang , Lei Fumin , Li Dongming , Qu Yanhua 
Published: April 2021

AbstractCorticosteroid-binding globulin (CBG) is a high-affinity plasma protein that binds glucocorticoids (GCs) and regulates their biological activities. The structural and functional properties of CBG are crucial to understanding the biological actions of GCs in mediating stress responses and the underlying mechanisms. In response to stress, avian CBGs modulate the free and bound fractions of plasma corticosterone (CORT, the main GC), enabling them to mediate the physiological and behavioral responses that are fundamental for balancing the trade-off of energetic investment in reproduction, immunity, growth, metabolism and survival, including adaptations to extreme high-elevation or high-latitude environments. Unlike other vertebrates, avian CBGs substitute for sex hormone-binding globulin (SHBG) in transporting androgens and regulating their bioavailability, since birds lack anShbggene. The three-dimensional structures of avian and mammalian CBGs are highly conserved, but the steroid-binding site topographies and their modes of binding steroids differ. Given that CBG serves as the primary transporter of both GCs and reproductive hormones in birds, we aim to review the biological properties of avian CBGs in the context of steroid hormone transportation, stress responses and adaptation to harsh environments, and to provide insight into evolutionary adaptations in CBG functions occurred to accommodate physiological and endocrine changes in birds compared with mammals.
Hyperoxemia during resuscitation of trauma patients and increased intensive care unit length of stay: inverse probability of treatment weighting analysis
Authors:   on behalf of the Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) Study Group, Yamamoto Ryo , Fujishima Seitaro , Sasaki Junichi , Gando Satoshi , Saitoh Daizoh , Shiraishi Atsushi , Kushimoto Shigeki , Ogura Hiroshi , Abe Toshikazu , Mayumi Toshihiko , Kotani Joji , Nakada Taka-aki , Shiino Yasukazu , Tarui Takehiko , Okamoto Kohji , Sakamoto Yuichiro , Shiraishi Shin-Ichiro , Takuma Kiyotsugu , Tsuruta Ryosuke , Masuno Tomohiko , Takeyama Naoshi , Yamashita Norio , Ikeda Hiroto , Ueyama Masashi , Hifumi Toru , Yamakawa Kazuma , Hagiwara Akiyoshi , Otomo Yasuhiro 
Published: April 2021

Abstract
Background
Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes.

Methods
A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016–2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO2 of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models.

Results
Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10–21) vs 23 (16–26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12–22) vs 23 (19–26), p = 0.004], but not among those intubated at the ED [18 (9–20) vs 15 (8–23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay.

Conclusions
Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED.

Trial registration
UMIN-CTR, UMIN000019588. Registered on November 15, 2015.
Emergency surgery for splenic flexure cancer: results of the SFC Study Group database
Authors:   on behalf of the SFC Study Group, de’Angelis Nicola , Espin Eloy , Ris Frederic , Landi Filippo , Le Roy Bertrand , Coccolini Federico , Celentano Valerio , Gurrado Angela , Pezet Denis , Bianchi Giorgio , Memeo Riccardo , Vitali Giulio C. , Solis Alejandro , Denet Christine , Di Saverio Salomone , de’Angelis Gian Luigi , Kraft Miquel , Gonzálvez-Guardiola Paula , Stakelum Aine , Catena Fausto , Fuks David , Winter Des C. , Testini Mario , Martínez-Pérez Aleix 
Published: April 2021

Abstract
Background
The effectiveness of surgical treatment for splenic flexure carcinomas (SFCs) in emergency settings remains unexplored. This study aims to compare the perioperative and long-term outcomes of different alternatives for emergency SFC resection.

Method
This multicenter retrospective study was based on the SFC Study Group database. For the present analysis, SFC patients were selected if they had received emergency surgical resection with curative intent between 2000 and 2018. Extended right colectomy (ERC), left colectomy (LC), and segmental left colectomy (SLC) were evaluated and compared.

Results
The study sample was composed of 90 SFC patients who underwent emergency ERC (n = 55, 61.1%), LC (n = 18, 20%), or SLC (n = 17, 18.9%). Bowel obstruction was the most frequent indication for surgery (n = 75, 83.3%), and an open approach was chosen in 81.1% of the patients. A higher incidence of postoperative complications was observed in the ERC group (70.9%) than in the LC (44.4%) and SLC groups (47.1%), with a significant procedure-related difference for severe postoperative complications (Dindo-Clavien ≥ III; adjusted odds ratio for ERC vs. LC:7.23; 95% CI 1.51-34.66; p = 0.013). Anastomotic leakage occurred in 8 (11.2%) patients, with no differences between the groups (p = 0.902). R0 resection was achieved in 98.9% of the procedures, and ≥ 12 lymph nodes were retrieved in 92.2% of patients. Overall and disease-free survival rates at 5 years were similar between the groups and were significantly associated with stage pT4 and the presence of synchronous metastases.

Conclusion
In the emergency setting, ERC and open surgery are the most frequently performed procedures. ERC is associated with increased odds of severe postoperative complications when compared to more conservative SFC resections. Nonetheless, all the alternatives seem to provide similar pathologic and long-term outcomes, supporting the oncological safety of more conservative resections for emergency SFCs.
Long non-coding RNA AFAP1-AS1 facilitates ovarian cancer progression by regulating the miR-107/PDK4 axis
Authors: Liu Bao , Yan Li , Chi Yugang , Sun Yuhan , Yang Xiaoyu 
Published: April 2021

Abstract
Background
Abnormally expressed in various tumors, long non-coding RNAs (lncRNAs) feature prominently in tumor development, yet little is still known regarding the functional roles of lncRNA AFAP1 antisense RNA 1 (AFAP1-AS1) in ovarian cancer (OC).

Methods
The relative expression levels of lncRNA AFAP1-AS1, microRNA (miR)-107 and pyruvate dehydrogenase kinase isozyme 4 (PDK4) mRNA were assessed by quantitative real-time PCR. PDK4, PCNA and cyclin D1 expression levels were determined using Western blot analysis. Bioinformatics analysis and dual-luciferase gene reporter assay were conducted for identifying and validating the binding sequences between AFAP1-AS1 and miR-107, as well as between miR-107 and PDK4. Cell counting kit-8 assay was employed for detecting cell proliferation. Cell migration and invasion abilities were examined using Transwell assays.

Results
The present study revealed that AFAP1-AS1 expression was elevated in OC cells and tissues. AFAP1-AS1 expression and FIGO stage were positively correlated. AFAP1-AS1 knockdown repressed OC cell proliferation, migration and invasion. AFAP1-AS1 functioned as a sponge of miR-107, and miR-107 reversed the effects of AFAP1-AS1 on OC cells. It was validated that miR-107 was able to bind to PDK4, and AFAP1-AS1 regulated PDK4 expression by competitively binding with miR-107. Additionally, miR-107 modulated OC cell proliferation, migration and invasion via targeting PDK4.

Conclusions
LncRNA AFAP1-AS1 serves as a tumor driver in the pathogenesis of OC via the miR-107/PDK4 axis.
CD36 polymorphisms and the age of disease onset in patients with pathogenic variants within the mutation cluster region of APC
Authors: Connor T , McPhillips M , Hipwell M , Ziolkowski A , Oldmeadow C , Clapham M , Pockney PG , Lis E , Banasiewicz T , Pławski A , Scott RJ 
Published: April 2021

Abstract
Background
Familial adenomatous polyposis (FAP) is an autosomal dominant condition that predisposes patients to colorectal cancer. FAP is the result of a loss of APC function due to germline pathogenic variants disrupting gene expression. Genotype-phenotype correlations are described for FAP. For example attenuated forms of the disease are associated with pathogenic variants at the 5’ and 3’ ends of APC whilst severe forms of the disease appear to be linked to variants occurring in the mutation cluster region (MCR) of the gene. Variants occurring in the MCR are phenotypically associated with hundreds to thousands of adenomas carpeting the colon and rectum and patients harbouring changes in this region have a high propensity to develop colorectal cancer. Not all patients who carry pathogenic variants in this region have severe disease which may be a result of environmental factors. Alternatively, phenotypic variation observed in these patients could be due to modifier genes that either promote or inhibit disease expression. Mouse models of FAP have provided several plausible candidate modifier genes, but very few of these have survived scrutiny. One such genetic modifier that appears to be associated with disease expression is CD36. We previously reported a weak association between a polymorphism in CD36 and a later age of disease onset on a relatively small FAP patient cohort.

Methods
In the current study, we enlarged the FAP cohort. 395 patients all carrying pathogenic variants in APC were tested against three CD36 Single Nucleotide Polymorphisms (SNP)s (rs1049673, rs1761667 rs1984112), to determine if any of them were associated with differences in the age of disease expression.

Results
Overall, there appeared to be a statistically significant difference in the age of disease onset between carriers of the variant rs1984112 and wildtype. Furthermore, test equality of survivor functions for each SNP and mutation group suggested an interaction in the Log Rank, Wilcoxon, and Tarone-Ware methods for rs1049673, rs1761667, and rs1984112, thereby supporting the notion that CD36 modifies disease expression.

Conclusions
This study supports and strengthens our previous findings concerning CD36 and an association with disease onset in FAP, AFAP and FAP-MCR affected individuals. Knowledge about the role CD36 in adenoma development may provide greater insight into the development of colorectal cancer.
Hesperidin alleviates insulin resistance by improving HG-induced oxidative stress and mitochondrial dysfunction by restoring miR-149
Authors: Tian Miao , Han Yu-Bo , Zhao Cheng-Cheng , Liu Li , Zhang Fu-Li 
Published: April 2021

Abstract
Background
Hesperidin, a natural flavanone, has been proven to have multiple protective effects in diabetic rats, such as antioxidant, anti-inflammatory and anti-apoptotic effects. However, the molecular mechanisms underlying the effects of hesperidin are not well elucidated.

Methods
LO2 cells were stimulated with high glucose (HG, 33 mM) for 24 h to establish a model of oxidative stress. Then, cell viability was determined using the MTT assay. The antioxidant activities, including the reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, mitochondrial membrane potential (MMP) and adenosine-triphosphate (ATP) production, were measured with the corresponding kits. The levels of gene expression, protein expression and methylation were detected using qRT-PCR, western blotting and methylation-specific PCR (MSP) assays, respectively.

Results
Compared to the NG treatment, hesperidin treatment increased the viability and improved the oxidative stress, mitochondrial dysfunction and insulin resistance of HG-treated LO2 cells, and these effects were correlated with heightened SOD and GPx activities, increased MMP level and ATP generation, reduced MDA, ROS and glucose levels, and activated GSK3β/AKT and inactivated IRS1 signals. Mechanistically, hesperidin treatment enhanced the miR-149 expression level by reducing its promoter methylation by inhibiting DNMT1. Importantly, knockdown of miR-149 obviously abolished the biological roles of hesperidin.

Conclusions
Our findings demonstrated that hesperidin treatment ameliorated HG-induced insulin resistance by reducing oxidative stress and mitochondrial dysfunction partly by suppressing DNMT1-mediated miR-149 silencing.
Estimands in epigenome-wide association studies
Authors: Kruppa Jochen , Sieg Miriam , Richter Gesa , Pohrt Anne 
Published: April 2021

Abstract
Background
In DNA methylation analyses like epigenome-wide association studies, effects in differentially methylated CpG sites are assessed. Two kinds of outcomes can be used for statistical analysis: Beta-values and M-values. M-values follow a normal distribution and help to detect differentially methylated CpG sites. As biological effect measures, differences of M-values are more or less meaningless. Beta-values are of more interest since they can be interpreted directly as differences in percentage of DNA methylation at a given CpG site, but they have poor statistical properties. Different frameworks are proposed for reporting estimands in DNA methylation analysis, relying on Beta-values, M-values, or both.

Results
We present and discuss four possible approaches of achieving estimands in DNA methylation analysis. In addition, we present the usage of M-values or Beta-values in the context of bioinformatical pipelines, which often demand a predefined outcome. We show the dependencies between the differences in M-values to differences in Beta-values in two data simulations: a analysis with and without confounder effect. Without present confounder effects, M-values can be used for the statistical analysis and Beta-values statistics for the reporting. If confounder effects exist, we demonstrate the deviations and correct the effects by the intercept method. Finally, we demonstrate the theoretical problem on two large human genome-wide DNA methylation datasets to verify the results.

Conclusions
The usage of M-values in the analysis of DNA methylation data will produce effect estimates, which cannot be biologically interpreted. The parallel usage of Beta-value statistics ignores possible confounder effects and can therefore not be recommended. Hence, if the differences in Beta-values are the focus of the study, the intercept method is recommendable. Hyper- or hypomethylated CpG sites must then be carefully evaluated. If an exploratory analysis of possible CpG sites is the aim of the study, M-values can be used for inference.
Pleuritis associated with immunoglobulin G4-related disease under normal thoracoscopic findings: a case report
Authors: Shimada Hiroki , Kato Yuto , Okuda Miyuki , Fukuda Koji , Tanaka Nobuya , Okuda Yutaro , Yoshizawa Akihiko 
Published: April 2021

Abstract
Background
Immunoglobulin G4 (IgG4)-related disease is a chronic inflammatory disease that was recognized in 2011. Pleuritis associated with IgG4-related disease is rare and can be difficult to diagnose. Although there have been previous reports on pleuritis associated with IgG4-related disease by thoracoscopic findings, this is the first to observe pleuritis with IgG4-related disease from normal pleural thoracoscopic findings.

Case presentation
A 70-year-old Japanese female treated for breast cancer 33 years ago was referred to our hospital complaining of dyspnea on exertion. Chest computed tomography (CT) revealed left pleural effusion that was exudative and predominant with lymphocytes, elevated adenosine deaminase (ADA) and Class III cytology (malignancy suspected). Subsequently, thoracoscopic pleural biopsy was performed for definitive diagnosis. Although pleural macroscopic findings appeared normal, we performed pleural biopsy at random sites. This patient was negative for mycobacterium tuberculosis, and neither granulomas nor malignant cells were found in the collected specimens. An infiltration of inflammatory cells, mainly plasma cells and lymphocytes, was observed. Immunostaining revealed the number of IgG4-positive plasma cells was 102/high power field (HPF), and the percentage of IgG4 positive/immunoglobulin G (IgG)-positive cells was 41.4%. Since IgG4 serum levels were high and IgG4-related submandibular sialadenitis was also observed, a definitive diagnose of pleuritis associated with IgG4-related disease was confirmed.

Conclusions
We diagnosed pleuritis associated with IgG4-related disease by thoracoscopic pleural biopsy samples taken from a visually normal pleura. Although exudative pleural effusion with high ADA and lymphocyte predominance is a characteristic of tuberculous pleuritis, other diseases might be present. Since thoracoscopy can increase the diagnostic yield, pleural biopsy should be considered even if thoracoscopic pleural findings are deemed normal.
Assessing the calibration in toxicological in vitro models with conformal prediction
Authors: Morger Andrea , Svensson Fredrik , Arvidsson McShane Staffan , Gauraha Niharika , Norinder Ulf , Spjuth Ola , Volkamer Andrea 
Published: April 2021

AbstractMachine learning methods are widely used in drug discovery and toxicity prediction. While showing overall good performance in cross-validation studies, their predictive power (often) drops in cases where the query samples have drifted from the training data’s descriptor space. Thus, the assumption for applying machine learning algorithms, that training and test data stem from the same distribution, might not always be fulfilled. In this work, conformal prediction is used to assess the calibration of the models. Deviations from the expected error may indicate that training and test data originate from different distributions. Exemplified on the Tox21 datasets, composed of chronologically released Tox21Train, Tox21Test and Tox21Score subsets, we observed that while internally valid models could be trained using cross-validation on Tox21Train, predictions on the external Tox21Score data resulted in higher error rates than expected. To improve the prediction on the external sets, a strategy exchanging the calibration set with more recent data, such as Tox21Test, has successfully been introduced. We conclude that conformal prediction can be used to diagnose data drifts and other issues related to model calibration. The proposed improvement strategy—exchanging the calibration data only—is convenient as it does not require retraining of the underlying model.
Analytic and numerical solutions of discrete Bagley–Torvik equation
Authors: Meganathan Murugesan , Abdeljawad Thabet , Motawi Khashan M. , Britto Antony Xavier Gnanaprakasam , Jarad Fahd 
Published: April 2021

AbstractIn this research article, a discrete version of the fractional Bagley–Torvik equation is proposed:$$ \nabla _{h}^{2} u(t)+A{}^{C} \nabla _{h}^{\nu }u(t)+Bu(t)=f(t),\quad t>0, $$∇h2u(t)+AC∇hνu(t)+Bu(t)=f(t),t>0,where$0<\nu <1$0<ν<1or$1<\nu <2$1<ν<2, subject to$u(0)=a$u(0)=aand$\nabla _{h} u(0)=b$∇hu(0)=b, withaandbbeing real numbers. The solutions are obtained by employing the nabla discrete Laplace transform. These solutions are expressed in terms of Mittag-Leffler functions with three parameters. These solutions are handled numerically for some examples with specific values of some parameters.
Adverse childhood experiences and psychological distress among higher education students in Southeast Nigeria: an institutional-based cross-sectional study
Authors: Agbaje Olaoluwa Samson , Nnaji Chinwe Patience , Nwagu Evelyn Nwanebe , Iweama Cylia Nkechi , Umoke Prince Christian Ifeanachor , Ozoemena Lawretta Eyuche , Abba Charles Chike 
Published: April 2021

Abstract
Background
Exposure to adverse childhood experiences (ACEs) constitutes public health problems linked to adverse mental outcomes such as psychological distress during adulthood. This study examines the prevalence of ACEs and psychological distress and explores the association between ACEs and psychological distress and demographic factors among young adults.

Methods
We conducted a cross-sectional study of 330 students from May 2018 to July 2018. The participants completed the Adverse Childhood Experiences International Questionnaire (ACE-IQ), Kessler Psychological Distress Scale (K10), and the sociodemographic profile scale. We used descriptive statistics to describe the prevalence of ACEs and psychological distress in our sample. After adjusting for the demographic covariates, ACEs’ association with psychological distress was determined using binary and multivariate logistic regressions.

Results
A total of 203 students with a mean age of 20.76 ± 2.73 years completed the study. The total mean ACE score was 4.58 ± 1.59, and the total mean psychological distress score was 20.76 ± 6.31. Most of the participants (86.7%) experienced ACEs, 14.8% reported experiencing one ACE, 30.5% reported experiencing 2–3 ACEs, and 41.3% reported experiencing 4+ ACEs. Further, about 85% of the youth have experienced at least one form of sexual abuse during childhood, and females reported a higher number of ACEs than males. Sexual abuse (OR = 2.36; 95% CI: 2.36, 7.65), physical neglect (OR = 2.87; 95% CI: 1.57, 5.31), overall ACE exposure (OR = 6.66; 95% CI: 2.41, 18.42), having 1 ACE (OR = 4.40; 95% CI: 1.32, 14.70), having 2–3 ACEs (OR = 4.13; 95% CI: 1.39, 12.29), and having 4+ (OR = 11.67; 95% CI: 3.95, 34.45) were significantly associated with psychological distress.

Conclusions
ACEs are prevalent among young adults and are associated with psychological distress in adulthood. Furthermore, parental factors are associated with ACEs and psychological distress. Thus, implementation of school, community-and facility-based routine mental health screening programs is essential for prompt identification, prevention, and treatment of youth with childhood adversities and poor mental health outcomes.