bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis by modulating mitochondrial function
Authors: Jiang Xianxing , Zhao Qian , Dong Jiale , Chen Hui , Yu Huan , Ye Shuyin , Yu Shuangjin , Song Nazi , Xu Hongjiao , Luo Zhiteng , Chen Guodong , Wang Rui 
Published: February 2022

Abstract
GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR) are critical for the maintenance of glucose and energy homeostasis, but their roles in chronic kidney disease (CKD) are still unknown. Herein we found that the expression of GLP-1R and GCGR was lower in kidney from patients with CKD than in control individuals and was correlated with disease severity. RNA-seq analysis showed that adeno-associated viral vector serotype 9-GLP-1R or GCGR small hairpin RNA (AAV9-GLP-1R or GCGR shRNA) treatment in db/db mice exhibited more advanced diabetic nephropathy than wild-type mice. We also found that GLP-1R mainly expressed in glomeruli and GCGR expressed in both glomeruli and tubuli renales. Based on the importance of GLP-1R and GCGR in CKD, we design and report a new monomeric peptide, 1907-B, with agonism at the GLP-1R and GCGR that have more prolonged half-time than long-acting semaglutide in cynomolgus rats or monkeys (~2-3 fold) and exhibit better therapeutic contribution to CKD than best-in-class monoagonists, semaglutide or glucagon in db/db mice and unilateral ureter obstruction (UUO) mice. Various loss-of-function models, including selective pharmacological blockade and genetic knockdown, confirmed that the effects of 1907-B on improving glucose control and ameliorating the diabetic nephropathy in db/db mice were mediated through GLP-1 and glucagon signaling, whereas its action on inhibiting renal fibrosis in UUO mice was predominantly mediated through glucagon signaling. Mechanistically, 1907-B activated downstream cAMP-PKA pathway to promote mitochondrial biogenesis and bioenergetics, as well as to attenuate renal oxidative stress under chronic hyperglycemia via stimulating GLP-1R and GCGR simultaneously. Furthermore, 1907-B had crucial protection roles against inflammation via NFκB pathway and renal fibrosis via TGF-β-SMAD pathway. Thus 1907-B, via direct kidney (GCGR) and part-glomerulus (GLP-1R) effects, exerts multifactorial improvement in renal injuries and is a more effective and promising therapeutic option for the treatment of CKD.
Vapor-Phase Substrate Nitroreductase Reaction and its Application as TNT Electrochemical Gas Sensor
Authors: Puttasakul Tasawan , Tancharoen Chompoonuch , Sukjee Wannisa , Sangma Chak 
Published: February 2022

Abstract
Nitroreductase (NTR) is an enzyme with a specific activity to nitroaromatic reduction. Some nitroaromatic explosives are exploited by terrorists. Among these materials, 2,4,6- trinitrotoluene (TNT) is a major high explosive which makes detection of TNT an important research topic. TNT vapor detection by gas sensor is an approach under investigated for many years. Even though, there is a limited success at present, in part, due to the ultra-low volatility nature of TNT. In this work, we propose an application of the NTR reaction in a hydrogel gas sensor to detect TNT vapor. Firstly, NTR activity in the hydrogel was confirmed by adding TNT and 2,4-dinitrotoluene (DNT) solutions to an NTR-hydrogel sensor following by cyclic voltammetry (CV) experiments. Then, the other CV experiments were carried out with gas phase samples. The CV graphs of NTR-hydrogels detecting vapors containing the explosive substrates and negative controls were compared. Results showed that the signal from the nitroaromatics increased with exposure time where the TNT signal was the highest of all tested compounds. The gas sensor was sensitive enough to detect TNT gas presented in an ambient air at room temperature.
Prevalence, Risk Factors and Remedies for Psychiatric Illnesses among Students in Higher Education: A Comprehensive Study in University of Ruhuna
Authors: Wijesekara Patikiri Arachchige Don Shehan Nilmantha 
Published: February 2022

Abstract
There is no comprehensive study on the mental health of Sri Lankan undergraduate in higher education as most existing studies have been done for medical students only. It is unknown how academic and environmental factors contribute for the prevalence of psychiatric illnesses. Further, there is no sufficient information on the student/university based remedies to reduce the psychological distress of students. This research is carried out to find the overall psychological distress, well-being, prevalence percentages of psychiatric illnesses, associated risk factors and student/university remedies to overcome them. All 13 psychiatric illnesses were found with a moderate correlation among diseases having a mean prevalence percentage of 25.92 and standard deviation of 12.93 despite the prevalence of well-being factors among students and only 8 % are clinically diagnosed. 89 % of the students were suffering from at least one psychiatric illness and 68 % were found to be psychologically distressed. Sets of overall and individual demographic, academic and environmental risk factors contributing for the prevalence of a psychiatric illness in general and in particularly were identified respectively after a Binary logistic regression analysis. 61 % of the students don’t receive psychiatric help from the university and are using their own remedies.
The Effect of Reducing Dietary Energy on Growth Performance, Intestinal Morphology and Intestinal Peptide and Amino Acid Transporters in Broiler Chicks
Authors: Mahdavi Reza , Harsini Shahab Ghazi , Piray Ali Hossein 
Published: February 2022

Abstract
This study evaluated the effect of two levels of metabolizable energy (2950 and 2850 kcal/kg) on performance, intestinal morphology, and mRNA abundance of peptide (PepT1) and amino acid transporters (b0,+ AT, B0AT, y+LAT1 and CAT1) in broilers during the starter period (0-10 days of age). This is the first reported in this case i human or animals case. Two hundred and seventy day old male Ross 308 broilers were used according to a completely randomized design with two treatments, where each treatment applied to 9 replicate pens with 15 birds in each. The outcome variables were measured at the end of the starter phase. The mRNA abundance of PepT1, b0,+ AT, B0AT, y+LAT1 and CAT1 were assayed using real-time PCR. The results showed that the body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were not affected by the dietary treatments (P>0.05). Jejunal mRNA levels of the b0,+AT and B0AT decreased as metabolizable energy level decreased from 2950 to 2850 kcal/kg (P≤0.05). The transport systems PepT1, CAT1, and y+LAT1 were not affected by the dietary treatments (P>0.05). There were no significant difference in villus height (VH), villus width (VW), villus surface area (VSA), crypt depth (CD), and villus height to crypt depth ratio (VCR) between treatments (P>0.05). These results demonstrated that dietary content of metabolizable energy affected the expression of amino acid transporters to modulate absorption of nutrients in broilers.
Morphological and endogenous phytohormone changes during long-term embryogenic cultures in Korean pine
Authors: Liang Yan , Xu Xin , Shen Hailong , Gao Meiling , Zhao Yan , Bai Xue 
Published: February 2022

Abstract
Somatic embryogenesis (SE) is a biotechnological tool with high application potential for in vitro propagation and regeneration of conifers species. However, in SE of Korean pine, a dominant species of the natural mixed coniferous and broadleaf forests of the temperate forests in Northeast China, decreasing embryogenic potential was found in embryogenic callus (EC) with successive subcultures, especially when the cultures were maintained for more than 5-6 months, which is one of the most significant problems preventing commercial implementation of the SE technique. Aiming to investigate the morphological and the endogenous phytohormone changes associated with the decreasing embryogenic potential of Korean pine, here, we compared seven types of calli during long-term embryogenic culture. It was found that both the external morphological characteristics and internal cell structure were significantly different among the different types of calli. Specifically, similar to their zygotic counterparts of conifer trees, the calli with high embryogenic potential were characterized by a higher number of designated proembryogenic masses (PEMs) structure. In addition, surface of this types of callus was covered with a large amount of mucilaginous extracellular matrix (ECM), which could further differentiate into globular embryos containing the embryonal masses (EM) and embryonic tube (ET) structure.In contrast, in those low embryogenic potential calli, we observed disintegrated PEMs structure, a large amount of irregularly shaped cells, and degraded cells, which failed to form somatic embryos. The endogenous hormone results showed that high levels of ABA were beneficial for promoting early somatic embryo differentiation in Korean pine, but maintaining high embryogenic potential required moderate levels of IAA and low levels of ZR. Additionally, a high ratio of IAA / ABA and MeJA / ABA was conducive to maintaining high embryogenic potential, whereas a low ratio of IAA / ABA and MeJA / ABA were effective for early somatic embryos morphological differentiation. This study demonstrates morphological and physiological characteristics of the embryogenesis potential of Korean pine calli.
Clinical assessment, gait analysis and reliability of measurement with the G walk inertial sensor in subjects with ankle fracture 6 months after surgery.
Authors: Fernández-Gorgojo Mario , Salas-Gómez Diana , Sánchez-Juan Pascual , Barbado David , Laguna-Bercero Esther , Pérez-Núñez Maria Isabel 
Published: February 2022

Abstract
Background: Ankle fractures can cause significant functional impairment in the short and long term. In recent years, gait analysis using inertial sensors has gained special relevance as a reliable measurement system.Objectives: In patients with bimalleolar ankle fracture, to identify the differences between the operated and healthy ankle in the spatial-temporal gait parameters and plantar pressures; likewise, to study their relationship with clinical parameters and functional scales. Finally, to assess the reliability of a single inertial sensor, placed on the lumbar spine, in our study population.Design: Cross-sectional study.Methods: Twenty-two subjects with bimalleolar ankle fractures were included in the study. An analysis of the spatial-temporal gait parameters and plantar pressures was carried out using an inertial system (G-WALK) and a pressure platform (P-WALK). Sociodemographic and clinical information was previously collected. Differences between the operated and healthy ankle were studied for each variable and their correlation with clinical measures and functional scales; then, a multiple linear regression analysis was performed with the variables that showed a significant correlation. Finally, the intra-session test-retest reliability of the G Walk was calculated using the intraclass correlation coefficient (ICC2,1) and the standard error of measurement (SEM).Results: Statistically significant differences were found for all spatial-temporal gait parameters and dynamic plantar pressures, except for double support (-1%; p=.267). Differences were also found for clinical measures, except for ADD strength (0.6%; p=.491). Effect sizes for gait variables ranged from 0.25 to 1.02 and for clinical variables ranged from 0.15 to 2.30. The highest degree of correlation of clinical measures and functional scales was obtained with speed, cadence, stride time, and propulsion. Intra-session test-retest reliability was high to excellent (0.84<ICC>0.98). Speed, stride length, and propulsion obtained the lowest SEM scores.Conclusions: In our study population, the analysis of spatial-temporal gait parameters and dynamic plantar pressures show an evident asymmetry between both limbs; likewise, they correlate moderately with ankle range of motion, hip abductor strength, and the AOFAS scale. The G-WALK inertial sensor can be considered a reliable gait measurement system in this population.
Cluster Analysis Applied to Climatology: A New Approach to Detect Changes in Precipitation
Authors: Medeiros Susane Eterna Leite , Nilo Priscila Farias , Silva Wallysson Klebson de Medeiros , Santos Paula Rose de Araújo , Silva Louise Pereira da , Abrahão Raphael 
Published: February 2022

Abstract
This work proposes a novel method for the application of cluster analysis to climatology. The new method groups similar years regarding total values of precipitation and distribution throughout the year. The most recent and oldest years are then compared to examine changes in the distribution pattern. The Ward’s method was used to compose hierarchical clusters. Trend analysis encompassed the Mann-Kendall and Sen's slope tests to complement and compare the results. This test characterizing a simple random series. As a form of exemplification, the proposed method was applied to historical data from seven weather stations located in northeastern Brazil. Significant trends of both increase and reduction in precipitation were observed, depending on the station studied. Even for statistically non-significant trends, the new cluster analysis enabled the verification of more subtle changes in precipitation. This new approach to cluster analysis can provide a broader view on how changes in precipitation patterns are occurring.
Low-Intensity Pulsed Ultrasound Promotes Cell Viability And Inhibits Apoptosis of H9C2 Cardiomyocytes In 3D Bioprinting Scaffolds Via PI3K-Akt And ERK1/2 Pathways
Authors: Hu Yugang , Jia Yan , Wang Hao , Cao Quan , Yang Yuanting , Zhou Yanxiang , Tan Tuantuan , Huang Xin , Zhou Qing 
Published: February 2022

Abstract
Purpose: This study was conducted to investigate whether low-intensity pulsed ultrasound (LIPUS) promotes myocardial cell viability in three-dimensional (3D) cell-laden gelatin methacryloyl (GelMA) scaffolds. Methods: Cardiomyoblasts (H9C2s) were mixed in 6% (w/v) GelMA bio-inks and printed using extrusion-based 3D bioprinting. The scaffolds were exposed to LIPUS with different parameters or sham-irradiated to optimize the LIPUS treatment. The viability of H9C2s was measured using Cell Counting Kit-8 (CCK8), cell cycle, and live and dead cell double staining assays. Western blot analysis was performed to determine the protein expression levels. Results: We successfully fabricated 3D bio-printed cell-laden GelMA scaffolds. CCK8 and live and dead cell double-staining assays indicated that the optimal conditions for LIPUS were a frequency of 0.5 MHz and exposure time of 10 min. Cell cycle analysis showed that LIPUS promoted the entry of cells into the S and G2/M phases from the G0/G1 phase. Western blot analysis revealed that LIPUS promoted the phosphorylation and activation of ERK1/2 and PI3K-Akt. The ERK1/2 inhibitor (U0126) and PI3K inhibitor (LY294002) significantly reduced LIPUS-induced phosphorylation of ERK1/2 and PI3K-Akt, respectively, which in turn reduced the LIPUS-induced viability of H9C2s in 3D bio-printed cell-laden GelMA scaffolds. Conclusions: A frequency of 0.5 MHz and exposure time of 10 min for LIPUS exposure can be adapted to achieve optimized culture effects on myocardial cells in 3D bio-printed cell-laden GelMA scaffolds via the ERK1/2 and PI3K-Akt signaling pathways.
SNPs Cumulating to Genetic Variation for Fertility in Crossbred (Bos taurus X Bos indicus) Bull Spermatozoa
Authors: Sinha Manish Kumar , Kumaresan Arumugam , Talluri Thirumala Rao , King John Peter Ebenezer Samuel , Prakash Mani Arul , Nag Pradeep , Paul Nilendu , Raval Kathan , Kamaraj Elango , V Aranganathan 
Published: February 2022

Abstract
Purpose: The objective of the present study is to identify important polymorphisms at single nucleotide in Holstein crossbred bull spermatozoa and to identify genetic variants significantly influence or associated to bull fertility. Methods: Spermatozoa from high- (HF) and low-fertile (LF) breeding bulls were subjected to high throughput Next-generation sequencing to identify important SNPs and novel variants associated with fertility.Results: A total of 77,036 genome wide SNPs were identified in the crossbred bull spermatozoa with a minimum read depth of 20, and among them, 10,269 were observed to be novel variants. A total of 42,290 and 34,748 variants were recorded in HF and LF bulls respectively, among which 6115 and 4673 were found to novel in respective group. Higher number of SNPs and Indels were identified in HF compared to LF bulls. GO analysis of filtered genes with significant variation in HF bulls indicated their enrichment in various important pathways like oxidative phosphorylation and metabolic pathways. On the other hand, GO analysis of filtered genes with significant variation in LF bulls revealed their involvement in Ca2++ ion binding, structural constituent of ribosome, and biological processes like translation and ribosomal small subunit assembly. Conclusions: The study identified SNPs in candidate genes including TPT1, BOLA-DRA, CD74, RPS17, RPS28, RPS29, RPL14, RPL13 and RPS27A, which are linked to sperm functionality, survival, protection from oxidative stress and bull fertility. The identified SNPs could be used as a tool for identification and selection of bulls for high fertility upon validation in large number of bulls
Clinical Staging and Genetic Profiling of Korean Patients with Primary Lymphedema Using Whole-Exome Sequencing: Preliminary Results
Authors: Seo Soo Hyun , Lee Seung Joon , Park Joseph Kyu-hyung , Yang Eun Joo , Kim Boram , Lee Jee-Soo , Kim Man Jin , Park Sung Sup , Seong Moon-Woo , Myung Yujin 
Published: February 2022

Abstract
Lymphedema is a progressive disease caused by lymphatic flow blockage in the lymphatic pathway. Primary (hereditary) lymphedema is caused by genetic mutations without secondary causes. However, the underlying cause of primary lymphedema remains obscure, and gene sequencing studies on a sizable patient cohort are lacking. We performed clinical profiling on Korean primary lymphedema patients based on their phenotypes and using lymphoscintigraphy and made genetic diagnoses using a next-generation sequencing panel consisting of 60 lymphedema-related genes. Of 27 patients, 21% had lymphedema of the upper extremities, 81% had lymphedema of the lower extremities, and two patients had lymphedema in both. Based on International Society of Lymphology staging, 14, 10, and 3 patients had stage 3, 2, and 1 lymphedema, respectively. Genetic abnormalities were identified in six patients: a pathogenic variant of CELSR1 in two patients, variants of uncertain significance (VUSs) of CELSR1 in two patients, a VUS of SOS1 in one patient, and a pathogenic variant of MPI and VUSs of TIE1, FLT4, and PIEZO1 in one patient. The clinical and genetic profile of hereditary lymphedema reported here is the first such data series reported in South Korea. Our study highlights the need for genetic screening in primary lymphedema diagnosis.
The youth mental health crisis during the COVID-19 pandemic: The role of school closures
Authors: Felfe Christina , Saurer Judith , Schneider Patrick , Vornberger Judith , Klotzbuecher Valentin , Erhart Michael , Kaman Anne , Sieberer Ulrike Ravens 
Published: February 2022

Abstract
The youth mental health crisis has become so acute during the COVID-19 pandemic that a coalition of U.S. pediatric health experts has declared it a national emergency1. To which extent this crisis can be attributed to the pandemic or the different pandemic measures is unknown. School closures are among the most heavily debated pandemic measures, with insufficient evidence on their costs2,3,4,5. We seek to narrow this blind spot, by compiling data on the manifold school closure and re-opening strategies implemented across the federal states of Germany at the onset of the pandemic and combining it with data from a nationwide, population-based, longitudinal survey on youth mental health and the largest crisis helpline for children and adolescents. We show that prolonged school closures led to a significant deterioration in youth health-related quality of life, precipitating first signs of mental health problems. Effects were most severe among boys, less mature adolescents, and families with limited living space. Young people also increasingly sought support from crisis helplines to discuss arising family and friendship problems. Importantly, the effects persist even when abstracting from the overall strain imposed by the pandemic or further pandemic measures. Indeed, school closures explain around two thirds of the aggravation of the youth mental health crisis throughout the first pandemic wave and there is no sign for a swift recovery.
Quality of life, levels of anxiety and depression among Sudanese patients with surgical stoma in Khartoum state, Sudan.
Authors: Abdelbagi Alnazeer Y. , Musa Razaz Mahde Esmaeel , Salih Mugahid A , M.A.Shaaban Kamil 
Published: February 2022

Abstract
Background: The objectives of this study are to assess the quality of life, levels of anxiety, and depression among Sudanese ostomates with special emphasis on sociodemographic data and ostomy-related data.Methods: This is a facility-based cross-sectional study in Khartoum state between 2018 and 2019. 100 patients participated in the study with a response rate of 80 in seven hospitals throughout Khartoum state. Standardized fecal incontinence quality of life (FIQOL) and hospital anxiety and depression scale (HADS) questionnaires were used and data obtained were analyzed by multiple statistical tests to identify any group differences and associations to the sociodemographic dataResults: Quality of life total score was found to be below the average. Depression scale scores at the average, and religious score account for the worst. While there is a strong correlation between the QOL subscales, there was no significant association between quality of life score and the sociodemographic data. Regarding anxiety and depression levels 51.3% of the participants are normal for anxiety level while 25% and 23.8% were borderline and abnormal respectively. For depression level, the score was 45% normal, 26.3% borderline and 28.8% were abnormal. neither some significant association nor subgroup differences were found regarding sociodemographic and ostomy-related data.Conclusions: Respondents had a quality of life below the average and high levels of anxiety and depression. Religious and spiritual QOL is marginally influenced by the intestinal stoma, qualitative comments also lend insight to the spiritual aspect. this finding can assist in the provision of holistic care in our stoma patients.