bluuebunny/crossref_metadata_2025_split huggingface dataset:
SFPQ Rescues F508del-CFTR Expression and Function in Cystic Fibrosis Bronchial Epithelial Cells
Authors: Kumar Parameet , Soni Dharmendra Kumar , Sen Chaitali , Larsen Mads B , Mazan-Mamczarz Krystyna , Piao Yulan , De Supriyo , Gorospe Myriam , Frizzell Raymond A. , Biswas Roopa 
Published: April 2021

Abstract
Cystic Fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear RNA-binding protein (RBP) implicated in the regulation of gene expression pathways and intracellular trafficking. Here, we investigated the role of SFPQ in the regulation of the expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508del-CFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease. Our findings provide new insights into SFPQ-mediated molecular mechanisms and point to possible novel epigenetic therapeutic targets for CF and related pulmonary diseases.
Meta-QTLs, Ortho-MetaQTLs and Candidate Genes for Grain yield and Associated Traits in Wheat (Triticum aestivum L.)
Authors: Saini Dinesh Kumar , Srivast Puja , Pal Neeraj , Gupta P. K. 
Published: April 2021

Abstract
The present study involved meta-QTL analysis based on 8,998 QTLs, including 2,852 major QTLs for grain yield (GY) and its following ten component/related traits: (i) grain weight (GWei), (ii) grain morphology related traits (GMRTs), (iii) grain number (GN), (iv) spikes related traits (SRTs), (v) plant height (PH), (vi) tiller number (TN), (vii) harvest index (HI), (viii) biomass yield (BY), (ix) days to heading/flowering and maturity (DTH/F/M) and (x) grain filling duration (GFD). The QTLs used for this study were retrieved from 230 reports involving 190 mapping populations (1999–2020), which also included 19 studies involving durum wheat. As many as 141 meta-QTLs were obtained with an average confidence interval of 1.37 cM (reduced 8.87 fold), the average interval in the original QTL being > 12.15 cM. As many as 63 MQTLs, each based on at least 10 original QTLs were considered to be the most stable and robust with thirteen identified as breeder’s meta-QTL. Meta-QTLs (MQTLs) were also utilized for identification of as many as 1,202 candidate genes (CGs), which also included 18 known genes. Based on a comparative genomics strategy, a total of 50 wheat homologues of 35 rice, barley and maize yield-related genes were also detected in these MQTL regions. Moreover, taking the advantage of synteny, a total of 24 ortho-MQTLs were detected at co-linear regions between wheat with barley, rice and maize. The present study is the most comprehensive till date, and first of its kind in providing stable and robust MQTLs and ortho-MQTLs, thus providing useful information for future basic studies and for marker-assisted breeding for yield and its component traits in wheat.
Characterization of the Gut Microbiota in Patients with Primary Sclerosing Cholangitis Compared to Inﬂammatory Bowel Disease and Healthy Controls
Authors: Ostadmohammadi Samaneh , Azimirad Masoumeh , Houri Hamidreza , Naseri Kaveh , Javanmard Ehsan , Mirjalali Hamed , Yadegar Abbas , Sadeghi Amir , Aghdaei Hamid Asadzadeh , Zali Mohammad Reza 
Published: April 2021

Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. Its aetiology remains largely unknown, although frequent concomitant inﬂammatory bowel disease (IBD) hints towards common factors underlying intestinal and bile duct inﬂammation. Herein, we aimed to explore the relative abundance of fecal microbiota in PSC-IBD patients compared to IBD-only subjects and healthy controls.We included 14 PSC-IBD patients, 12 IBD patients, and 8 healthy controls (HCs). A quantitative real-time PCR (qPCR) assay was to determine a selection of bacterial phyla, families, and genera.Relative abundance of taxa showed that Bacteroidetes was the most abundant phylum among the patients with PSC-IBD (29.46%) and also HCs (39.34%), whereas the bacterial species belonging to the phylum Firmicutes was the most frequent group in IBD-only subjects (37.61%). The relative abundance of Enterobacteriaceae family was higher among PSC-IBD (3%) than HCs (0.5%), and thus, could be used as a PSC-associated microbial signature.Our findings showed that intestinal microbiota composition in PSC-IBD patients was completely different from that of IBD-only patients. Further studies using large-scale cohorts should be performed to better describe the contribution of the gut microbiota to PSC pathogenesis with underlying IBD.
How to Evaluate Digital Leadership: A Cross-sectional Study
Authors: Claassen Kevin , Anjos Dominique Rodil Dos , Kettschau Jan , Broding Horst Christoph 
Published: April 2021

Abstract
Background: With the increasing digitalization of the working environment, the demands on managers are changing fundamentally to the point of an emerging field of research in digital leadership. Municipal administrations are particularly affected by the digital transformation processes. Therefore, a score to measure the construct of digital leadership competence in the context of virtual-based workstation was developed and tested.Methods: Based of an online survey with n = 546 employees at virtual-based workstations in municipal administrations in 2020, the instrument is tested regarding selectivity (coefficients), dimensionality (principal component analysis), homogeneity (inter-product-moment correlations), reliability (Cronbach's α) and construct validity (correlation with general leadership skills).Results: The instrument can be considered selective, one-dimensional, homogeneous, reliable and constructively valid in the sense of the formulated hypotheses. By integrating the employees‘ perspective, the instrument aims to be one of the first of its kind to initiate a scientific further discourse. Among other things, the categorization of the co-determination component as either traditional or digital leadership can be discussed.Conclusions: The developed instrument for measuring digital leadership performs well concerning the aspects of discriminatory power, one-dimensionality, homogeneity, reliability as well as construct validity. It aims to induce further research and a scientific discourse on the topic of health-oriented leadership within the world of work 4.0.
Effect of Fungal Endophytes on Plant Growth and Nutrient Uptake in Trifolium Subterraneum and Poa Pratensis as Affected by Plant Host Specificity
Authors: García-Latorre Carlos , Rodrigo Sara M. , SANTAMARIA OSCAR 
Published: April 2021

Abstract
The introduction of well-adapted species, such as Trifolium subterraneum and Poa pratensis, might enhance the forage yield and quality of dehesas pastures for feeding livestock. However, the climatic hardness and poor soils in these agrosystems may limit plant establishment and development. Since fungal endophytes have been found to alleviate the environmental stresses of their host, the aim of this study was to assess the effect of five isolates on forage yield, nutritive value and plant mineral uptake after their inoculation in the two above-mentioned plant species. Two experiments were established (under greenhouse and field conditions) using plants inoculated with two isolates in 2012/2013 (Epicoccum nigrum, Sporormiella intermedia) and three isolates in 2013/2014 (Mucor hiemalis, Fusarium equiseti, Byssochlamys spectabilis). Thus, F. equiseti (E346) increased the herbage yield of T. subterraneum under greenhouse conditions, B. spectabilis was found to improve the forage quality of T. subterraneum by reducing fibre content and of P. pratensis by increasing crude protein. Also, S. intermedia increased the mineral uptake of Ca, Cu, Mn, Pb, Tl and Zn in subclover and M. hiemalis, the uptake of K and Sr in Kentucky bluegrass. These results evidenced the potential of the studied fungal endophytes to enhance herbage yield and the forage nutritional value, although further studies should include all of the intended forage species as certain host specificity in the effect was observed.
Lag Between COVID-19 Cases and Subsequent Deaths
Authors: Donovan Sara , Brett-Major David , Lawler James V. 
Published: April 2021

Abstract
Background: Observed COVID-19 cases and deaths are frequently used as independent factors to justify the use or de-escalation of non-pharmaceutical interventions. To investigate and describe the temporal relationship between changes in epidemic curves for COVID-19 cases and deaths, a longitudinal analysis of these metrics was performed for 16 states in the United States and three countries.Results: The analysis performed demonstrates a considerable, consistent lag between a surge in COVID-19 cases and the subsequent rise in attributable deaths, with approximately a month-long lag observed.Conclusions: The time lag identified must be incorporated in health emergency decision making in order to avoid the pre-mature de-escalation of disease mitigation measures.
Role of Jasmonic and Salicylic Acid on Enzymatic Changes in The Root of Two Alyssum Inflatum Náyr. Populations Exposed to Nickel Toxicity
Authors: Kakavand Shiva Najafi , Karimi Naser , Ghasempour Hamid-Reza , Raza Ali , Chaichi Mehrdad , Modarresi Masoud 
Published: April 2021

Abstract
Salicylic acid (SA) and jasmonic acid (JA) as plant growth regulators (PGRs) have the potential to ameliorate plant development and tolerance to deleterious effects of toxic metals like nickel (Ni). Therefore, the current study was carried out to evaluate SA and JA's interactive effect on the root antioxidative response of two Alyssum inflatum Nyár. populations against Ni-toxicity. Two A. inflatum species under Ni-stress conditions (0, 100, 200, and 400 µM) were exposed to alone or combined levels of SA (0, 50, and 200 µM) and JA (0, 5, and 10 µM) treatments. Results showed that high Ni doses reduced the roots fresh weight (FW) in two populations than control; however, the use of external PGRs had ameliorated roots biomass by mitigated Ni-toxicity. Under Ni toxicity, SA and JA, especially their combination, induced high Ni accumulation in plants' roots. Moreover, the application of SA and JA alone, as well as combined SA + JA, was found to be effective in the scavenging of hydrogen peroxide (H2O2) by improving the activity of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in both populations under Ni-toxicity. Overall, our results manifest that SA and JA's external use, especially combined SA + JA treatments, ameliorate root biomass and plant tolerance by restricting translocation Ni to the shoot, accumulating in roots, and also enhancing antioxidant defense systems.
Potential Threats of Nanoplastic Accumulation in Human Induced Pluripotent Stem Cells
Authors: Jeong Hyejoong , Kim Wijin , Choi Daheui , Heo Jiwoong , Han Uiyoung , Jung Se Yong , Park Hee Ho , Hong Sung-Tae , Park Ju Hyun , Hong Jinkee 
Published: April 2021

Abstract
Background: Micro- and nanoplastics (NPs) produced from the bulk fragmentation are rampant in the world by enormous plastic trash everyday life. NPs can be exposed to humans through a variety of routes, including inhalation and intake. The threat to humans from NPs is increasing invisibly. Nowadays, many people are concerned about human safety and health, but few are reported about the effects of NP on humans. To overcome the limitations in human studies, human induced pluripotent stem cells (hiPSCs) were used as an optimal in vitro platform to investigate developmental toxicology and subtle changes on cellular functions in terms of differentiation potential throughout a long-term culture. Results: Negatively charged polystyrene nanoplastics (PS NPs) were used to exclude acute toxic issues of surface charge and investigate the impact of the NP's size and nature during bioaccumulation. Intracellular observations revealed that NPs up to 1000 nm were over-internalized into single cells within 48 h, and smaller NPs demonstrated greater potency at decreasing number of viable cells by a strong correlation with the number of NPs on an equal mass basis. Also, PS NPs caused a significant reduction in self-renewal capacity of hiPSCs for 48 h. After the cells were exposed to PS NPs for 48 to 96 h at the beginning of the differentiation process, NPs accumulated in hiPSC did not render cellular functions vulnerable or adversely affect EB formation, EB-mediated differentiation, and neural lineage differentiation for up to 14 days.Conclusion: This study confirmed that hiPSC exposure to polystyrene nanoplastics results in acute toxicity and non-significant long-term effects on cellular functions. This report is important for understanding the developmental toxicology of nanoplastics and the origin of disease.
The Top 100 Cited Articles in Osteonecrosis of the Femoral Head: a Bibliometric Analysis
Authors: Zhang Yumin , Wang Yakang , Chen Juan , Cheng Qianyue , Zhang Binfei , Hao Linjie , Ma Tao , Qin Siqing , Song Wei , Wen Pengfei 
Published: April 2021

Abstract
Background: The number of articles of clinical and basic research for osteonecrosis of the femoral head (ONFH) is increasing, to our knowledge, there is still a lack of bibliometric analysis on ONFH articles. The purpose of this study was to identify the top 100 cited (T100) articles related to ONFH research and analyze the characteristics and qualities of these articles.Methods: The T100 articles on ONFH were retrieved from the Web of Science database. The information about each article including citations, titles, authors, journals, countries, institutions, and keywords, was recorded for bibliometric analysis. Results: The T100 articles related to ONFH were mainly published from 1991 to 2010 (n=70), and originated from 24 countries. The USA, China, and Japan were the most productive countries in this regard. The most prolific institution was the University of Pennsylvania from the USA with 6 publications and 742 citations. The most-cited article was published in 1995 by Professor Steinberg ME. The five most frequently occurring keywords were “femoral head”, “osteonecrosis”, “core decompression”, “total hip arthroplasty” and “follow up”. The keywords like "bone tissue engineering" and "extracorporeal shock wave" have emerged in recent years.Conclusions: The USA, China, and Japan contributed greatly in terms of the T100 articles. The outcomes of core decompression and total hip arthroplasty gathered most research interests. In recent years, bone tissue engineering and extracorporeal shock wave have become new trends. However, the mechanism of ONFH is still unclear.
Neuronal induction of BNIP3-mediated mitophagy slows systemic aging in Drosophila
Authors: Schmid Edward , Pyo Jung-Hoon , Walker David 
Published: April 2021

Abstract
The effects of aging on the brain are widespread and present at both the cellular and functional level. Mitochondrial dysfunction is a hallmark of brain aging, but, the interplay between mitochondrial quality control, neuronal aging, and organismal health is not well understood. Here, we show that aging leads to a decline in mitochondrial autophagy (mitophagy) in the Drosophila brain and a concomitant increase in mitochondrial content. We find that induction of BCL2-interacting protein 3 (BNIP3), a mitochondrial outer membrane protein, in the adult nervous system induces mitophagy and prevents the accumulation of dysfunctional mitochondria in the aged brain. Importantly, neuronal induction of BNIP3-mediated mitophagy increases organismal longevity and healthspan. Furthermore, neuronal BNIP3-mediated mitophagy improves mitochondrial homeostasis and proteostasis in aged muscle, indicating cell non-autonomous effects. In addition, neuronal BNIP3-mediated mitophagy improves intestinal homeostasis in aged flies. Our findings identify BNIP3 as a novel therapeutic target to counteract brain aging and prolong overall organismal health with age.
Association of Gait With Global and Domain-specific Cognitive Function Among Community-dwelling Older Adults: A Cross-sectional Study
Authors: HAO WEN , Zhao Wenjing , Kimura Takashi , Ukawa Shigekazu , Kadoya Ken , Kondo Katsunori , Tamakoshi Akiko 
Published: April 2021

Abstract
Background: Gait is associated with cognitive function and is a trait marker of dementia; however, research on gait and cognitive function usually concentrates on several individual gait parameters. This study used wearable sensors to measure gait parameters in different aspects and comprehensively explored the association of gait with global cognitive function and domain-specific cognitive function.Methods: The data of this cross-sectional study were obtained from 236 community-dwelling Japanese older adults (125 men and 111 women) aged 70–81 years. Gait was measured by asking participants to walk a 6-meter course and back using the Physilog® sensors (GaiUp®, Switzerland). Global cognitive function and cognitive domains were evaluated by face-to-face interviews using the Japanese version of the Montreal Cognitive Assessment. Twenty gait parameters were summarized as independent gait factors using factor analysis. A generalized linear model and linear regression model were used to explore the relationship of gait with global cognitive function and domain-specific cognitive function adjusted for several confounding factors.Results: Factor analysis yielded four gait factors: general cycle, initial contact, propulsion, and mid-swing. Among them, general cycle factor was significantly associated with global cognitive function (β=-0.565, [-0.967, -0.163]), executive function (P=0.012), and memory (P=0.045); initial contact was associated with executive function (P=0.019).Conclusion: Better gait was related to better cognitive function, especially the general cycle, which was correlated with both global and domain-specific cognitive function. The predictive value should be examined in future cohort studies.
An Open-Label Prospective Pilot Trial of Nucleus Accumbens Deep Brain Stimulation for Children with Autism Spectrum Disorder and Severe, Refractory Self-Injurious Behaviour: Study Protocol
Authors: Yan Han , Siegel Lauren , Breitbart Sara , Gorodetsky Carolina , Fasano Alfonso , Rahim Aliya , Loh Alvin , Kulkarni Abhaya V. , Ibrahim George M. 
Published: April 2021

Abstract
Background
Children and youth with Autism Spectrum Disorder (ASD) may manifest self-injurious behaviours (SIB) that may become severe and refractory with limited pharmacologic or behavioural treatment options. Here, we present the protocol of a prospective, mixed-methods study to assess the safety and efficacy of deep brain stimulation (DBS) of the nucleus accumbens (NAcc) for children and youth with ASD and severe, refractory SIB.
Methods
This is a prospective, single-center, single-cohort, open-label, non-randomized pilot trial of 6 patients. Participants will be recruited through specialized behavioural clinics with persistent severe and refractory SIB following standard and intensive interventions. Following NAcc-DBS, participants will be enrolled in the study for 12 months. The primary objectives of the study are safety and feasibility, assessed by rate of recruitment and identification of factors impacting adherence to follow-up and study protocol. Treatment efficacy will be assessed by changes in the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), the Behaviour Problems Index (BPI), the Inventory of Statements about Self-Injury (ISAS) and the Repetitive Behaviour Scale-Revised (RBS-R) questionnaires. Additional clinical outcomes will be assessed, including measures of participant and caregiver quality of life, actigraph measurements, and positron emission tomography (PET) changes following DBS.
Discussion
This study will be the first to evaluate the effect of DBS of the NAcc on a pediatric population in a controlled, prospective trial. Secondary outcomes will improve the understanding of behavioural, neuro-imaging and electrophysiologic changes in children with ASD and SIB treated with DBS. This trial will provide an estimated effect size of NAcc-DBS for severe refractory SIB in children with ASD in preparation for future comparative trials.
Trial Registration
Registration on ClinicalTrials.gov was completed on June 12 of 2019 with the Identifier: NCT03982888. https://clinicaltrials.gov/ct2/show/NCT03982888
Elevated thyroid hormone caused by high concentrate diet participates in hepatic metabolic disorders in dairy cows
Authors: Chen Qu , Wu Chen , Yao Zhihao , Cai Liuping , Ni Yingdong , Mao Shengyong 
Published: April 2021

Abstract
Background
Feeding a high concentrate diet is widely used to satisfy high milk yields, however, if used over a longer term it can cause metabolic disorders. Abnormal secretion of hormones is one of the important causes of metabolic disorders caused by high concentrate diet, however, the related research is still limited. In total, 12 mid-lactating dairy cows were randomly assigned to HC group (60% concentrate of dry matter, n = 6) or LC group (40% concentrate of dry matter, n = 6). All cows were slaughtered at the 21st day, and blood and liver samples were collected.
Results
Compared with LC group, HC group showed reduced serum triglyceride (TG), free fatty acid (FFA), total cholesterol (TC), low density lipoprotein (LDL-C), and increased liver glycogen and glucose (P < 0.05). Real-time PCR results showed that genes related to gluconeogenesis, namely, glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) were significantly upregulated and accompanied greater gluconeogenic protein expression in HC group (P < 0.05). The expression of hepatic genes and proteins related to lipogensis, including sterol regulatory element-binding protein 1 (SREBP1), long-chain acyl-CoA synthetase 1 (ACSL1), and fatty acid synthase (FAS) were downregulated in HC group (P < 0.05). However, the expression of genes and proteins related to β-oxidation, including carnitine palmitoyltransferase 1α (CPT1α) and peroxisome proliferator activated receptor α (PPARα) were significantly increased in HC group (P < 0.05). The levels of serum cortisol, thyroxin (T4), triiodothyronine (T3), free triiodothyronine (FT3) and liver FT3 elevated significantly in HC group (P < 0.05). Moreover, the expression of thyroid hormone receptor (THR) upregulated at gene and protein levels (P < 0.05).
Conclusions
Taken together, this study first reports that abnormal secretion of TH induced by high concentrate diet participates in metabolic disorders, and it regulates glycometabolism and lipid metabolism through its actions on the liver in lactating dairy cows.