bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Nutritional, Lifestyle, and Metabolic Factors With Non-alcoholic Fatty Liver Disease: An Umbrella Review With More Than 380,000 Participants
Authors: Xia Yang , Wu Qijun , Dai Huixu , Lv Jiale , Liu Yashu , Sun Hui , Jiang Yuting , Chang Qing , Niu Kaijun , Zhao Yuhong 
Published: September 2021

Background &amp; Aims:Nonalcoholic fatty liver disease (NAFLD) is the most common liver injury. We performed this umbrella review of meta-analyses to summarize the evidence on the associations of nutritional, lifestyle, and metabolic factors with NAFLD.Methods:We searched the PubMed, Embase, and Web of Science databases from inception until July 2, 2020, to identify meta-analyses of observational studies which explored the associations of nutritional, lifestyle, and metabolic factors with NAFLD. Evidence levels were assessed using summary effect sizes, 95% prediction intervals, between-study heterogeneity, evidence of small-study effects, and evidence of excess significance bias for each meta-analysis. (No. of PROSPERO, CRD42020200124).Results:Twenty two risk or protective factors from 10 published meta-analyses were included and studied. Three risk factors (sugar-sweetened beverage consumption, serum fetuin-A, and waist circumference) with highly suggestive levels of evidence and three risk factors (soft drink consumption, former smoking, and body mass index) with suggestive levels of evidence were identified. Only two protective factors (physical activity and serum vitamin D level [among adults in Western countries]) with suggestive levels of evidence were identified. Furthermore, other six risk factors and two protective factors with weak levels of evidence were identified.Conclusions:We found varying levels of evidence of associations of nutritional, lifestyle, and metabolic factors and NAFLD. The results suggest that nutritional and lifestyle management should be considered as a major primary preventive strategy for NAFLD. Moreover, considering the low quality of included meta-analyses and limited area of research topics, future high-quality original studies and meta-analyses should be performed to study these associations.
Improving Prognosis of Surrogate Assay for Breast Cancer Patients by Absolute Quantitation of Ki67 Protein Levels Using Quantitative Dot Blot (QDB) Method
Authors: Hao Junmei , Lyu Yan , Zou Jiarui , Zhang Yunyun , Xie Shuishan , Jing Lili , Tang Fangrong , Lyu Jiahong , Zhang Wenfeng , Zhang Jianbo , Wang Xunting , Chen Kuisheng , Zhang Jiandi 
Published: September 2021

BackgroundImmunohistochemistry (IHC)-based surrogate assay is the prevailing method in daily clinical practice to determine the necessity of chemotherapy for Luminal-like breast cancer patients worldwide. It relies on Ki67 scores to separate Luminal A-like from Luminal B-like breast cancer subtypes. Yet, IHC-based Ki67 assessment is known to be plagued with subjectivity and inconsistency to undermine the performance of the surrogate assay. A novel method needs to be explored to improve the clinical utility of Ki67 in daily clinical practice.Materials and MethodsThe Ki67 protein levels in a cohort of 253 specimens were assessed with IHC and quantitative dot blot (QDB) methods, respectively, and used to assign these specimens into Luminal A-like and Luminal B-like subtypes accordingly. Their performances were compared with the Kaplan–Meier, univariate, and multivariate survival analyses of the overall survival (OS) of Luminal-like patients.ResultsThe surrogate assay based on absolutely quantitated Ki67 levels (cutoff at 2.31 nmol/g) subtyped the Luminal-like patients more effectively than that based on Ki67 scores (cutoff at 14%) (Log rank test, p = 0.00052 vs. p = 0.031). It is also correlated better with OS in multivariate survival analysis [hazard ratio (HR) at 6.89 (95% CI: 2.66–17.84, p = 0.0001) vs. 2.14 (95% CI: 0.89–5.11, p = 0.087)].ConclusionsOur study showed that the performance of the surrogate assay may be improved significantly by measuring Ki67 levels absolutely, quantitatively, and objectively using the QDB method.
MiR-1224 Acts as a Prognostic Biomarker and Inhibits the Progression of Gastric Cancer by Targeting SATB1
Authors: Han Guo-Dong , Sun Yuan , Hui Hong-Xia , Tao Ming-Yue , Liu Yang-Qing , Zhu Jing 
Published: September 2021

ObjectiveMiR-1224 has been reported to exhibit abnormal expression in several tumors. However, the expressing pattern and roles of miR-1224 in gastric cancer (GC) remain unclear. Our current research aimed to explore the potential involvement of miR-1224 in the GC progression.Materials and MethodsThe expression of miR-1224 was examined in tissue samples of 128 GC patients and cell lines by RT-PCR. Besides, the associations of miR-1224 expressions with clinicopathologic features and prognosis of GC patients were analyzed. Then, the possible influences of miR-1224 on cell proliferation and cell migration were determined. Afterward, the molecular target of miR-1224 was identified using bioinformatics assays and confirmed experimentally. Finally, RT-PCR and Western blot assays were performed to investigate the effect of the abnormal miR-1224 expression on the EMT and Wnt/β-catenin pathway.ResultsmiR-1224 was lowly expressed in the GC specimens and cell lines due to T classification and TNM stage. Survival assays demonstrated that GC patients with low expressions of miR-1224 possessed poor overall survivals. Moreover, in vitro and in vivo assays revealed that the overexpression of miR-1224 inhibited cell proliferation, migration, and invasion in GC cells. SATB homeobox 1 (SATB1) was verified as a direct target of miR-1224 in GC. Furthermore, β-catenin and c-myc were significantly inhibited in miR-1224-overexpression cells.ConclusionsOur findings highlight the potential of miR-1224 as a therapeutic target and novel biomarker for GC patients
Pediatric Telehealth Expansion in Response to COVID-19
Authors: Williams Stormee , Hill Kristina , Xie Luyu , Mathew M. Sunil , Ofori Ashley , Perry Tamara , Wesley Danielle , Messiah Sarah E. 
Published: September 2021

Introduction: Telehealth utilization has been steadily increasing for the past two decades and has been recognized for its ability to access rural and underserved populations. The advent of COVID-19 in March 2020 limited the feasibility of in-person healthcare visits which in turn increased telehealth demand and use. However, the long-term impacts of COVID-19 on the telehealth sector of the healthcare industry, and particularly on pediatric healthcare volume demand and subsequent expansion, are yet to be determined.Objective and Methods: To understand the impact of COVID-19 on telehealth utilization, volume demand, and expansion in one large pediatric healthcare system serving greater Dallas-Fort Worth, Texas, data on telehealth clinic visits by month, pre-COVID and post/current-COVID were compared. A quasi-experimental pretest-posttest design analysis compared telehealth visit counts from 54 ambulatory pediatric health specialties. Pre-post new patient counts were also analyzed via chi square.Results: Total telehealth visit counts significantly increased between March–October 2019 (2,033 visits) compared to March-October 2020 (54,276 visits). Mean monthly telehealth visits increased by 6,530 visits, or 2,569.75% over the same time period (p &lt; 0.0001). In October 2020, total telehealth visits were still 1,194.78% above 2019 levels (345 visits in 2019 vs. 4467 visits in 2020).Discussion: Results here show a substantial volume increase in telehealth-delivered pediatric healthcare and resource utilization as a response to COVID-19. This provides a template for permanent adoption of pediatric telehealth delivery post pandemic. Further investigation is needed to determine impacts upon resource allocation, processes, and general models and standard of care to assist facilities and programs to better address the needs of the pediatric populations they serve in the post-COVID era.
Modified Dual Hepatic Vein Anastomosis in Pediatric Living-Donor Liver Transplantation Using Left Lateral Segment Grafts With Two Wide Orifices
Authors: Hou Yuchen , Wan Ping , Feng Mingxuan , Qiu Bijun , Zhou Tao , Zhu Jianjun , Luo Yi , Zhang Jianjun , Xia Qiang 
Published: September 2021

Background: The anatomic variation of hepatic vein in the left lateral segment (LLS) increases the risk of outflow complication in pediatric living liver transplantation (LDLT). Here, we share a modified method for dual hepatic vein reconstruction in pediatric LDLT using LLS with two wide orifices.Methods: From Sep 2018 to Dec 2019, 434 pediatric LDLTs using LLS were performed in our center. Hepatic veins of grafts were classified into three types with emphasis on the number, size, and location of orifices at the cut surface: a single opening (type I, n = 341, 78.57%); two adjacent orifices (type II, n = 66, 15.21%); two wide orifices with orifices distances &lt;20 mm (type IIIa, n = 15, 3.46%); and two wide orifices with orifices distances &gt;20 mm (type IIIb, n = 12, 2.76%). Rv was defined as the ratio of diameter of V2 and V3 (refer to hepatic vein drained segments II and III). We developed a modified dual hepatic vein anastomosis to reconstruct outflow for type IIIb grafts with Rv ≤1. Briefly, the hepatic vein of segment II was anastomosed to the common stump of middle hepatic vein (MHV) and left hepatic vein (LHV), followed by unification of V3 and the longitudinal incision orifice in inferior venous cave (IVC).Results: During median follow-up of 15.6 months (7.5–22.9 months), no hepatic vein complications occurred.Conclusion: This novel modified dual hepatic vein anastomosis could serve as a feasible surgical option for type IIIb LLS grafts with Rv ≤1 in pediatric LDLT.
Safety, Tolerability, and Pharmacokinetics of a Novel Mitochondrial Modulator, TRC150094, in Overweight and Obese Subjects: A Randomized Phase-I Clinical Trial
Authors: Joshi Deepa , Jamadarkhana Prashant , Kumbhare Suchit , Singh Amarinder , Kotecha Jignesh , Bunger Deepak , Shiwalkar Ajay , Mohanan Anookh , Dutt Chaitanya 
Published: September 2021

TRC150094, a novel mitochondrial modulator, can restore metabolic flexibility by improving insulin resistance in preclinical studies. This study primarily aims to evaluate the safety, tolerability, and pharmacokinetics (PK) of oral TRC150094 after conducting two double-blind, randomized, Phase-I studies, single ascending dose (SAD) and multiple ascending dose (MAD), with n = 46, in overweight/obese adult and elderly subjects. In addition, the effect of TRC150094 on pharmacodynamic (PD) efficacy markers was evaluated. PK assessments, including maximum concentration (Cmax), area under the plasma concentration (AUC), time to Cmax (Tmax), and elimination half-life (t½), were assessed at pre-specified time points. PD assessments included apolipoprotein B (ApoB), triglycerides, hepatic fat by magnetic resonance spectroscopy (MRS) and cardiopulmonary exercise testing (CPET) parameters. TRC150094 was rapidly absorbed, and the AUC of TRC150094 increased in a dose-dependent manner across all doses in non-elderly and elderly cohorts. Cmax was more than the dose-proportional for all doses in all cohorts. Tmax ranged from 0.25 to 4 h, and t½ ranged from 15 to 18 h, making TRC150094 suitable for once-daily dosing. Food did not interfere with the overall absorption of the drug. The metabolites of TRC150094 were glucuronide and sulfate conjugates, and 20% of the drug was excreted unchanged in the urine. TRC150094 at 50 mg showed an improving trend in triglycerides. A significant reduction in Apo B was observed after 50 mg dose (−2.34 vs. 13.24%, p = 0.008), which was, however, not the case after 150 mg (8.78 vs. 13.24%, p = 0.1221). Other parameters such as hepatic fat and insulin sensitivity indices (HOMA-IR, MATSUDA Index derived from OGTT) showed an improving trend for the dose of 50 mg. In terms of safety, all the AEs reported were mild to moderate in severity. None of the adverse events was considered definitely or probably related to treatment, and there were no abnormal laboratory findings. In conclusion, the PK of TRC150094 was linear with no clinically significant food effect. TRC150094 and its metabolites suggest a lesser likelihood of drug-drug interactions. Overall, TRC150094 ensured safety and exhibited suitability for all subjects.Clinical Trial Registration: EUDRA CT: 2009-014941-10 (SAD) and CTR-India registration: CTRI/2009/091/000601 (MAD)
Mechanism of Ulcerative Colitis-Aggravated Liver Fibrosis: The Activation of Hepatic Stellate Cells and TLR4 Signaling Through Gut-Liver Axis
Authors: Liu Yu-Feng , Niu Guo-Chao , Li Chen-Yang , Guo Jin-Bo , Song Jia , Li Hui , Zhang Xiao-Lan 
Published: September 2021

Background:The progression of liver disorders is frequently associated with inflammatory bowel disease through the gut-liver axis. However, no direct evidence showed the mechanisms of ulcerative colitis (UC) in the development of liver fibrosisper se. Thus, this study aimed to evaluate the effects of UC on liver fibrosis and its potential mechanism in the experimental model.Methods:Male C57BL/6 mice were allocated into five groups (n= 10 per group) to receive either drinking water (control), 2% dextran sulfate sodium (DSS), olive oil, carbon tetrachloride (CCl4) or DSS + CCl4for 4 cycles. Blood was collected for biochemical analysis. Colons were excised for the evaluation of colon length and morphological score. Liver, colon, and mesenteric lymph nodes (MLNs) were collected for histopathological staining, expression analysis, and bacterial translocation assay to evaluate the inflammation, fibrosis, the activation of hepatic stellate cells (HSCs), and gut barrier function.Results:DSS caused severe colitis in mice treated or treated with CCl4, as evident from the elevation of disease activity index (DAI), histological abnormalities, and increased pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-17A). Histopathological staining revealed that DSS treatment aggravated the CCl4-induced extracellular matrix deposition, liver fibrosis, and inflammation in mice. Additionally, biochemical and expression analysis indicated the DSS treatment caused the increase of hydroxyproline and pro-inflammatory cytokines, as well as the abnormal liver function indexes in CCl4-induced mice. Gut barrier function was impaired in DSS- and DSS + CCl4-treated mice, manifesting as the increase in bacterial translocation and lipopolysaccharide level, and the reduction in tight junction proteins (occluding, claudin-1 and ZO-1) expression. Further, the activations of HSCs and TLR4 signaling pathway were observed after DSS + CCl4treatment, presenting with the increase in expression of α-SMA, vimentin, TGF-β, collagen type I, collagen type II, TIMP-2, TLR4, TRAF6, and NF-κB p65, and a decrease in GFAP and MMP-2 expression.Conclusion:The present study verified that UC aggravated CCl4-induced liver injury, inflammation, and fibrosis in mice through the gut-liver axis. Gut barrier dysfunction in UC leads to bacterial translocation and elevated lipopolysaccharide, which may promote the activation of TLR4 signaling and HSCs in the liver.
RENAISSANCE-HUMANISTIC CONCEPTS OF CULTURE OF PEDAGOGICAL DIALOGUE OF THE TEACHERS OF THE ORDER FROM THE SOCIETY OF JESUS IN EARLY MODERN TIMES
Authors: Basenko Ruslan 
Published: September 2021

A period of European Renaissance is the birth of the modern personality and virtues Renaissance Christian humanism is a model of ethical attitudes today. The first attempt of early modern European youth education in educational system of coordinates of Renaissance humanism, no doubt, was created within the youth Order of St. Ignatius.The proposed article is devoted to the analysis of verbal communicative competence of early modern Jesuit teachers. The author revealed the contents of value-semantic, spiritual and pedagogical concepts of educational communication in the Society of Jesuits, and proved that it was based on Renaissance and Christian- humanistic positions of “brilliance, beauty and sophistication” of the academic word, the skill of public speaking and high style and the art of eloquence of the early modern university speaker.The author concludes that the Jesuits interpreted pedagogically Renaissance and humanistic intellectual heritage to the implementation of the Order implementing schooling some semantic meaning loads of humanism in this article. Recognizing it as "imitation of ancient people", as an appeal to samples of ancient learning,fundamental virtues of the Society of Jesus proclaimed erudition, sophistication of Latin, intellectual culture, exquisite taste, eloquence, perfection scientist speech and public speaking, virtuous behavior. With the Renaissance and humanistic individualism priorities code integrity Jesuit added active devotion, diligence, active, creative enthusiasm and initiative, determination and zeal, compassion, rationality and prudence, the Jesuits appreciated the talent and abilities of youth, drawn attention to the need to care for the physical health etc. Etymological interpretation of humanity as humanity in correctional priorities Jesuits answered task of building virtues of modesty and politeness, prudent and tolerance, respect and attention for elders, love and kindness, ethics, partnership and unity.The article highlights and grounds the components of the Jesuit methodology of formation of conversational competencies in the youth of the Order (didactically and cognitive, rhetoric and stylistic, moral and aesthetic); the article also proves the sonority of the Jesuit practice of teaching literature with the didactic pedagogy of the European Renaissance. The conclusion was made about the significant role of socio- cultural, socio-integrating task and spiritual significance of educational communication of Jesuit teachers for implementation of the European Youth Policy of St. Ignatius rank in XVI – XVII centuries.
METHODS OF IMPROVING MUSICAL TRAINING OF FUTURE CHOREOGRAPHY TEACHERS
Authors: Xuefei He 
Published: September 2021

The author of the research paper states that the organization of the educational process of musical training becomes particularly urgent, which would be focused on the quality of choreographic education and raise the level of musical culture of the future choreography teachers. It is emphasized that musical training of future choreography teachers is developed and organized by a professor and is realized by a student through certain stages: 1) identification of the goal and planning of musical training; 2) organization of musical training of future choreography teachers; 3) carrying out musical training; 4) evaluation and correction of the results of musical training, that is determination of the music culture maturity levels. It is stated that the efficiency of improving the fundamentals of musical training of future choreography teachers when studying in higher educational institution largely depends on the determination of their tiered characteristics, i.e. on the phase of estimation and correction of the results of the musical training of future choreographers. The research paper deals with the algorithm of musical training of future choreography teachers, aimed at its improvement; components (motivational and orientation, cognitive and competence, creative and performing), criteria (motivational, cognitive, emotional, behavioral) and maturity levels (high, medium and low) of musical culture are determined. The methodology of improving musical training of future choreography teachers is suggested. This methodology to improve musical training of future choreography teachers is efficient, effective and coherent, all its components have a clear purpose, and they are in close relationship and are aimed at achieving the goal.
DEVELOPMENT OF MUSEUM PEDAGOGY IN UKRAINE: CULTURAL PRINCIPLES
Authors: Filipchuk Natalia 
Published: September 2021

The article describes the potential of museum pedagogy in the context of the problem of optimization of cultural and educational processes in Ukraine. It has been emphasized that educational institutions, scientific institutions must pay special attention to popularize museums, and the search for new forms of museum pedagogy, aimed at forming a society with a respectful attitude to the values of museum culture, and increasing its social status by means of development of citizens’ positive motivation, especially the youth. Museum pedagogy is primarily associated with the field of cultural and educational activities, which serves the school, educational institutions through contacts with pupils, students, and educators. This trend is traditional in the functioning of this form of communication, establishing contacts and dialogue between a museum institution and a person. The author argues that this established form of cultural and educational activities is not enough to give a description of museum pedagogy. An important component of museum work is also scientific and practical activity of a modern museum, focused on the study of cultural heritage, its historical, scientific, cognitive, educational, practical features, transfer of artistic experience through the pedagogical process. It has been determined that the education of a citizen is the most important mission of the museum. Museum pedagogy becomes a reality when a person acquires the status of participant in museum communication, and an employee of an institution, having come into contact with a person, can not be a culture educator and a teacher and a psychologist simultaneously, as he began to act in a complex social model of communication “person-person”. It turns out that in education an active introduction of museum pedagogy is needed to overcome the negative stated practice of isolating the cultural environment from educational institutions.
Deletion of Mocos Induces Xanthinuria with Obstructive Nephropathy and Major Metabolic Disorders in Mice
Authors: Sedda Delphine , Mackowiak Claire , Pailloux Julie , Culerier Elodie , Dudas Ana , Rontani Pauline , Erard Nicolas , Lefevre Antoine , Mavel Sylvie , Emond Patrick , Foucher Frederic , Le Bert Marc , Quesniaux Valerie F.J. , Mihatsch Michael J. , Ryffel Bernhard , Erard-Garcia Madeleine 
Published: September 2021

Key Points

A knockout mouse targeting the molybdenum cofactor sulfurase (Mocos) gene develops xanthinuria type II with lethal obstructive nephropathy.Xanthinuric Mocos knockout mice display moderate renal inflammation and fibrosis, normocytic anemia, and reduced detoxification defense systems.Purine, but also amino acid and phospholipid, metabolic pathways are altered in Mocos knockout kidneys.

Background
Xanthinuria type II is a rare autosomal purine disorder. This recessive defect of purine metabolism remains an under-recognized disorder.

Methods
Mice with targeted disruption of the molybdenum cofactor sulfurase (Mocos) gene were generated to enable an integrated understanding of purine disorders and evaluate pathophysiologic functions of this gene which is found in a large number of pathways and is known to be associated with autism.

Results

Mocos-deficient mice die with 4 weeks of age due to renal failure of distinct obstructive nephropathy with xanthinuria, xanthine deposits, cystic tubular dilation, Tamm–Horsfall (uromodulin) protein (THP) deposits, tubular cell necrosis with neutrophils, and occasionally hydronephrosis with urolithiasis. Obstructive nephropathy is associated with moderate interstitial inflammatory and fibrotic responses, anemia, reduced detoxification systems, and important alterations of the metabolism of purines, amino acids, and phospholipids. Conversely, heterozygous mice expressing reduced MOCOS protein are healthy with no apparent pathology.

Conclusions

Mocos-deficient mice develop a lethal obstructive nephropathy associated with profound metabolic changes. Studying MOCOS functions may provide important clues about the underlying pathogenesis of xanthinuria and other diseases requiring early diagnosis.