bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex and age differences in the association of fatty liver index-defined non-alcoholic fatty liver disease with cardiometabolic risk factors: a cross-sectional study
Authors: Fresneda Sergio , Abbate Manuela , Busquets-Cortés Carla , López-González Arturo , Fuster-Parra Pilar , Bennasar-Veny Miquel , Yáñez Aina M. 
Published: November 2022

Abstract
Background
Despite the extensive scientific evidence accumulating on the epidemiological risk factors for non-alcoholic fatty liver disease (NAFLD), evidence exploring sex- and age-related differences remains insufficient. The present cross-sectional study aims to investigate possible sex differences in the prevalence of FLI-defined NAFLD as well as in its association with common risk factors across different age groups, in a large sample of Spanish working adults.

Methods
This cross-sectional study included data from 33,216 Spanish adult workers (18–65 years) randomly selected during voluntary routine occupational medical examinations. Sociodemographic characteristics (age and social class), anthropometric (height, weight, and waist circumference) and clinical parameters (blood pressure and serum parameters) were collected. NAFLD was determined by the validated fatty liver index (FLI) with a cut-off value of ≥ 60. The presence of metabolic syndrome (MetS) was assessed according to the diagnostic criteria of the International Diabetes Federation. Cardiovascular risk was determined using the REGICOR-Framingham equation. The association between FLI-defined NAFLD and risk factors by sex and age was evaluated by multivariate logistic regression.

Results
The prevalence of FLI-defined NAFLD (FLI ≥ 60) was 19.1% overall, 27.9% (95% CI 23.3–28.5%) for men and 6.8% (95% CI 6.4–7.3%) for women and increasing across age intervals. As compared to women, men presented worse cardiometabolic and anthropometric profiles. The multivariate analysis model showed that hepatic steatosis assessed by FLI was strongly associated with age, HDL-cholesterol, social class, prediabetes, diabetes, prehypertension, hypertension, and smoking status for both men and women. The association between diabetes and hypertension with FLI-defined NAFLD was stronger in women than in men at both univariate and multivariate analyses.

Conclusions
Men presented a higher prevalence of NAFLD than women across all age intervals, as well as a worse cardiometabolic profile and a higher cardiovascular risk. Nevertheless, the association between FLI-defined NAFLD and diabetes or hypertension was significantly stronger in women than in men, possibly indicating that the presence of a dysmetabolic state might affect women more than men with regard to liver outcomes.
The balance between NANOG and SOX17 mediated by TET proteins regulates specification of human primordial germ cell fate
Authors: Li Zili , Fang Fang , Long Yuting , Zhao Qian , Wang Xiaotong , Ye Zhen , Meng Tianqing , Gu Xiuli , Xiang Wenpei , Xiong Chengliang , Li Honggang 
Published: November 2022

Abstract
Background
Human primordial germ cells (hPGCs) initiate from the early post-implantation embryo at week 2–3 and undergo epigenetic reprogramming during development. However, the regulatory mechanism of DNA methylation during hPGC specification is still largely unknown due to the difficulties in analyzing early human embryos. Using an in vitro model of hPGC induction, we found a novel function of TET proteins and NANOG in the hPGC specification which was different from that discovered in mice.

Methods
Using the CRISPR–Cas9 system, we generated a set of TET1, TET2 and TET3 knockout H1 human embryonic stem cell (hESC) lines bearing a BLIMP1-2A-mKate2 reporter. We determined the global mRNA transcription and DNA methylation profiles of pluripotent cells and induced hPGC-like cells (hPGCLCs) by RNA-seq and whole-genome bisulfite sequencing (WGBS) to reveal the involved signaling pathways after TET proteins knockout. ChIP-qPCR was performed to verify the binding of TET and NANOG proteins in the SOX17 promoter. Real-time quantitative PCR, western blot and immunofluorescence were performed to measure gene expression at mRNA and protein levels. The efficiency of hPGC induction was evaluated by FACS.

Results
In humans, TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) impaired the NODAL signaling pathway and impeded hPGC specification in vitro, while the hyperactivated NODAL signaling pathway led to gastrulation failure when Tet proteins were inactivated in mouse. Specifically, TET proteins stimulated SOX17 through the NODAL signaling pathway and directly regulates NANOG expression at the onset of hPGCLCs induction. Notably, NANOG could bind to SOX17 promoter to regulate its expression in hPGCLCs specification. Furthermore, in TKO hESCs, DNMT3B-mediated hypermethylation of the NODAL signaling-related genes and NANOG/SOX17 promoters repressed their activation and inhibited hPGCLC induction. Knockout of DNMT3B in TKO hESCs partially restored NODAL signaling and NANOG/SOX17 expression, and rescued hPGCLC induction.

Conclusion
Our results show that TETs-mediated oxidation of 5-methylcytosine modulates the NODAL signaling pathway and its downstream genes, NANOG and SOX17, by promoting demethylation in opposition to DNMT3B-mediated methylation, suggesting that the epigenetic balance of DNA methylation and demethylation in key genes plays a fundamental role in early hPGC specification.
Pterostilbene attenuates intrauterine growth retardation-induced colon inflammation in piglets by modulating endoplasmic reticulum stress and autophagy
Authors: Chen Yanan , Zhang Hao , Li Yue , Ji Shuli , Jia Peilu , Wang Tian 
Published: November 2022

Abstract
Background
Endoplasmic reticulum (ER) stress and autophagy are implicated in the pathophysiology of intestinal inflammation; however, their roles in intrauterine growth retardation (IUGR)-induced colon inflammation are unclear. This study explored the protective effects of natural stilbene pterostilbene on colon inflammation using the IUGR piglets and the tumor necrosis factor alpha (TNF-α)-treated human colonic epithelial cells (Caco-2) by targeting ER stress and autophagy.

Results
Both the IUGR colon and the TNF-α-treated Caco-2 cells exhibited inflammatory responses, ER stress, and impaired autophagic flux (P < 0.05). The ER stress inducer tunicamycin and the autophagy inhibitor 3-methyladenine further augmented inflammatory responses and apoptosis in the TNF-α-treated Caco-2 cells (P < 0.05). Conversely, pterostilbene inhibited ER stress and restored autophagic flux in the IUGR colon and the TNF-α-treated cells (P < 0.05). Pterostilbene also prevented the release of inflammatory cytokines and nuclear translocation of nuclear factor kappa B p65, reduced intestinal permeability and cell apoptosis, and facilitated the expression of intestinal tight junction proteins in the IUGR colon and the TNF-α-treated cells (P < 0.05). Importantly, treatment with tunicamycin or autophagosome-lysosome binding inhibitor chloroquine blocked the positive effects of pterostilbene on inflammatory response, cell apoptosis, and intestinal barrier function in the TNF-α-exposed Caco-2 cells (P < 0.05).

Conclusion
Pterostilbene mitigates ER stress and promotes autophagic flux, thereby improving colon inflammation and barrier dysfunction in the IUGR piglets and the TNF-α-treated Caco-2 cells.
Stem cell phenotype predicts therapeutic response in glioblastomas with MGMT promoter methylation
Authors: Lakis Nelli S. , Brodsky Alexander S. , Karashchuk Galina , Audesse Amanda J. , Yang Dongfang , Sturtevant Ashlee , Lombardo Kara , Wong Ian Y. , Webb Ashley E. , Anthony Douglas C. 
Published: November 2022

AbstractA growing body of evidence supports the presence of a population of cells in glioblastoma (GBM) with a stem cell-like phenotype which shares certain biological markers with adult neural stem cells, including expression of SOX2, CD133 (PROM1), and NES (nestin). This study was designed to determine the relationship between the expression of these stem cell markers and the clinical outcome in GBM patients. We quantified the intensity of expression of the proteins CD133 and SOX2 by immunohistochemistry (IHC) in a cohort of 86 patients with IDH-wildtype GBM, and evaluated patient outcomes using Kaplan–Meier and Cox proportional hazards analysis. In our patients, MGMT promoter methylation status and age were predictors of overall survival and progression free survival. The levels of SOX2 and CD133 were not associated with outcome in univariate analysis; however, stratification of tumors based on low or high levels of CD133 or SOX2 expression revealed that MGMT methylation was a predictor of progression-free survival and overall survival only for tumors with high levels of expression of CD133 or SOX2. Tumors with low levels of expression of CD133 or SOX2 did not show any relationship between MGMT methylation and survival. This relationship between MGMT and stem cell markers was confirmed in a second patient cohort, the TCGA dataset. Our results show that stratification of GBM by the level of expression of CD133 and SOX2 improved the prognostic power of MGMT promoter methylation status, identifying a low-expressing group in which the clinical outcome is not associated with MGMT promoter methylation status, and a high-expressing group in which the outcome was strongly associated with MGMT promoter methylation status. These findings support the concept that the presence of a high stem cell phenotype in GBM, as marked by expression of SOX2 or CD133, may be associated with the clinical response to treatment.
Weakening behavior of the shallow megasplay fault in the Nankai subduction zone
Authors: Roesner Alexander , Ikari Matt J. , Hüpers Andre , Kopf Achim J. 
Published: November 2022

AbstractThe Nankai Trough megasplay fault hosts diverse modes of fault slip, ranging from slow slip events to megathrust earthquakes, and is responsible for related phenomena such as tsunamis and submarine landslides. All types of slip events require some kind of frictional weakening process in order to nucleate and propagate. We tested fluid-saturated, powdered megasplay fault samples in a direct shear apparatus under effective normal stresses of 2–18 MPa to investigate their friction velocity- and slip-dependence. The experiments show that for short distances (1 mm) after a velocity step, there is an evolution from velocity weakening at low effective normal stress to velocity strengthening at high effective normal stresses. Over a longer distance (5 mm), large velocity weakening is observed over all tested effective normal stresses. In all experiments, slip weakening behavior occurred with relatively large weakening rates at low effective normal stresses and smaller weakening rates at higher effective normal stresses. Critical stiffnesses for slip instability were calculated for both the velocity and slip dependence of friction to determine their relative importance. At shallow depths, velocity weakening would be the main cause of frictional instability for both small and large slip perturbations, whereas at greater depth instability requires either slip weakening over small slip distances, or velocity weakening induced by larger slip. Regardless of the underlying mechanism, the observed slip instability at lower effective stresses increases the likelihood for fault slip events to travel to the seafloor which may cause submarine landslides and tsunamis.
Graphical Abstract
Minos and Restless transposon insertion mutagenesis of psychrotrophic fungus for red pigment synthesis adaptive to normal temperature
Authors: Lu Fengning , Ren Yanna , Ding Lulu , Lu Jian , Zhou Xiangshan , Liu Haifeng , Wang Nengfei , Cai Menghao 
Published: November 2022

AbstractThe polar psychrotrophic fungus Geomyces sp. WNF-15A can produce high-quality natural red pigment for the potential use as edible pigment. However, it shows low-temperature-dependent synthesis of red pigment, which limits its large-scale industrial applications due to the difficult and high-cost bioprocess control. This study aims to develop transposon-mediated mutagenesis methods to generate mutants that are able to synthesize red pigment at normal temperature. Four transposable systems, including single and dual transposable systems, were established in this fungus based on the Minos from Drosophila hydei and the Restless from Tolypocladium inflatum. A total of 23 production-dominant mutants and 12 growth-dominant mutants were thus obtained by constructed transposable systems. At 14 °C and 20 °C, the MPS1 mutant strain achieved the highest level of red pigment (OD520 of 43.3 and 29.7, respectively), which was increased by 78.4% and 128.7% compared to the wild-type, respectively. Of note, 4 mutants (MPS1, MPS3, MPS4 and MPD1) successfully synthesized red pigment (OD520 of 5.0, 5.3, 4.7 and 4.9, respectively) at 25 °C, which broke the limit of the wild-type production under normal temperature. Generally, the dual transposable systems of Minos and Restless were more efficient than their single transposable systems for mutagenesis in this fungus. However, the positive mutation ratios were similar between the dual and single transposable systems for either Minos or Restless. This study provides alternative tools for genetic mutagenesis breeding of fungi from extreme environments.
Graphical Abstract
Utility of melatonin in mitigating ionizing radiation-induced testis injury through synergistic interdependence of its biological properties
Authors: Amer Maggie E. , Othman Azza I. , Abozaid Hajer Mohammed , El-Missiry Mohamed A. 
Published: November 2022

AbstractBackgroundIonizing radiations (IR) have widespread useful applications in our daily life; however, they have unfavorable effects on reproductive health. Maintaining testicular health following IR exposure is an important requirement for reproductive potential. The current study explored the role of melatonin (MLT) in mitigating IR-induced injury in young adult rat testis.MethodsRats were given daily MLT (25 mg/kg) for 3 and 14 days after receiving 4 Gy γ-radiation.ResultsSerum MLT levels and other antioxidants, including glutathione content, and the activity of glutathione peroxidase and glutathione reductase in the testis of the irradiated rats were remarkably maintained by MLT administration in irradiated rats. Hence, the hydrogen peroxide level declined with remarkably reduced formation of oxidative stress markers, 4-hydroxynonenal, and 8-Hydroxy-2′-deoxyguanosine in the testis of irradiated animals after MLT administration. The redox status improvement caused a remarkable regression of proapoptotic protein (p53, Cyto-c, and caspase-3) in the testis and improved inflammatory cytokines (CRP and IL-6), and anti-inflammatory cytokine (interleukin IL-10) in serum. This is associated with restoration of disturbed sex hormonal balance, androgen receptor upregulation, and testicular cell proliferation activity in irradiated rats, explaining the improvement of sperm parameters (count, motility, viability, and deformation). Consequently, spermatogenic cell depletion and decreased seminiferous tubule diameter and perimeter were attenuated by MLT treatment post irradiation. Moreover, the testis of irradiated-MLT-treated rats showed well-organized histological architecture and normal sperm morphology.ConclusionsThese results show that radiation-induced testicular injury is mitigated following IR exposure through synergistic interdependence between the antioxidant, anti-inflammatory, anti-apoptotic, and anti-DNA damage actions of MLT.
Obesity and total joint arthroplasty: Does weight loss in the preoperative period improve perioperative outcomes?
Authors: Laperche Jacob , Feinn Richard , Myrick Karen , Halawi Mohamad J. 
Published: November 2022

Abstract
Background
The obese population is more likely to develop degenerative joint disease requiring total joint arthroplasty (TJA) and also experience increased rates of adverse post-surgical outcomes. This study assessed whether a quantifiable weight loss prior to TJA had any impact on perioperative and 30-day outcomes in obese patients.

Method
Using the American College of Surgeons-National Surgical Quality Improvement Program database, obese patients who underwent total hip or total knee arthroplasty and lost at least 10% of their total body weight prior to surgery were identified and matched to other obese individuals undergoing the same procedures without weight loss. Perioperative outcomes, including operative time, length of stay, discharge destination, or 30-day adverse events, including complications, re-admissions, re-operations, and mortality, were then compared using conditional Logistic regression analysis.

Results
Analysis showed no difference between the two groups in terms of operative time, length of stay, discharge destination, or 30-day adverse events, including complications, re-admissions, re-operations, and mortality.

Conclusion
The results of this study suggest that weight loss alone in the preoperative period may not be sufficient to mitigate the effects of obesity on immediate post-TJA outcomes.
Investigation of the performance of grouted couplers in vehicle impacted reinforced concrete ABC bridge piers
Authors: Roy Suman , Unobe Ikwulono D. , Sorensen Andrew D. 
Published: November 2022

AbstractIncreased dynamic impact on bridge piers caused by seismic events, blasts, and vehicular impact have become increasingly common. Recent research efforts indicate that code provisions for designing reinforced concrete members to withstand such dynamic loads are inadequate and need additional insights for this purpose. Numerous works have been undertaken to investigate reinforced concrete (RC) traditional bridge pier performance on high strain rate loading. However, little attention has been given to evaluate the performance of connections used in present day bridges including accelerated bridge constructions (ABC) to withstand vehicle impacts, and hence, is relatively unknown. In this study, the use of grouted couplers to contain the unbalanced moments resulting from vehicular impact forces exceeding the moment capacity of the reinforced concrete piers and avoiding extensive damage to the piers is investigated. A representative column, typical of those specified by state departments of transportation, is studied to determine the performance. The performance of the coupler is investigated for both dynamic and static combined stresses. Quasi-static to dynamic strain rates of steel reinforcement connected to the couplers is also evaluated. Quantifying the stresses and strains developed at coupler region from dynamic impact can help coupler manufacturers to optimize the strength properties, thus improving serviceability. This study investigated utilizing splice sleeves in mitigating the formation of plastic hinges, as well as addressing the essential properties of coupler sections required to adequately carry out this function, and will provide a useful design tool for the manufacturers, forensic structural engineers, and practitioners.
Investigating the relationship between autistic traits and symptoms and Catatonia Spectrum
Authors: Dell’Osso L. , Amatori G. , Massimetti G. , Nardi B. , Gravina D. , Benedetti F. , Bonelli C. , Luciano M. , Berardelli I. , Brondino N. , De Gregorio M. , Deste G. , Nola M. , Reitano A. , Muscatello M. R. A. , Pompili M. , Politi P. , Vita A. , Carmassi C. , Maj M. 
Published: November 2022

AbstractBackgroundIn recent years, numerous studies have highlighted the overlap between autism spectrum disorder (ASD) and catatonia, both from a clinical and pathophysiological perspective. This study aimed to investigate the relationship between the autism spectrum (autistic traits and ASD signs, symptoms, and behavioral manifestation) and Catatonia Spectrum (CS).MethodsA total sample of 376 subjects was distributed in four diagnostic groups. Subjects were assessed with the Structured Clinical Interview for DSM-5, Research Version, the Adult Autism Subthreshold Spectrum (AdAS Spectrum), and CS. In the statistical analyses, the total sample was also divided into three groups according to the degree of autism severity, based on the AdAS Spectrum total score.ResultsA statistically significant positive correlation was found between AdAS Spectrum and CS total score within the total sample, the gender subgroups, and the diagnostic categories. The AdAS Spectrum domains found to be significantly and strongly correlated with the total CS score were hyper–hypo reactivity to sensory input, verbal communication, nonverbal communication, restricted interests and rumination, and inflexibility and adherence to routine. The three groups of different autistic severity were found to be distributed across all diagnostic groups and the CS score increased significantly from the group without autistic traits to the group with ASD.ConclusionsOur study reports a strong correlation between autism spectrum and CS.
Changes in mental illness stigma over 30 years – Improvement, persistence, or deterioration?
Authors: Schomerus Georg , Schindler Stephanie , Sander Christian , Baumann Eva , Angermeyer Matthias C. 
Published: November 2022

Abstract

Background
Large efforts have been made to erase the stigma of mental illness, but it is unclear whether they have succeeded on a population level. We examine how attitudes toward people with depression or schizophrenia have evolved in Germany since 1990, and whether there are different developments for both disorders.

Methods
Using data from the three decades, four wave repeated cross-sectional representative population study in the “old” (western) states in Germany with surveys in 1990 (n = 2,044), 2001 (n = 4,005), 2011 (n = 1,984), and 2020 (n = 2,449), we calculate time-trends for social distance and emotional reactions toward someone with major depression or acute schizophrenia.

Results
Social distance worsened in six out of seven situations for schizophrenia, whereas improving in two out of seven situations for depression. Emotions related to fear and uneasiness increased for schizophrenia, whereas tending to decrease for depression. Pro-social reactions like the desire to help increased for depression, but decreased for schizophrenia. Initially observed differences, favoring depression over schizophrenia, widened over the 30-year study period. For schizophrenia, the biggest negative changes occurred between 1990 and 2001, whereas some improvements with regard to depression occurred more recently.

Conclusion
Contrary to expectations, stigma has become more severe regarding acute schizophrenia in Germany over the last 30 years, whereas only slightly improving for depression. The apparent normalization of mental health problems seems not to directly translate into improving attitudes toward people with severe mental illness. Re-focusing of anti-stigma efforts on people with severe mental illness seems necessary.