bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant CD137‐Fc, its synthesis, and applications for improving the immune system functions, such as tumor immunotherapy and to reduce the inflammation due to the novel coronavirus
Authors: Ajami Maryam , Nazari Mahboobeh , mahmoodzadeh Habibollah , Moazzeni Seyed Mohammad 
Published: May 2021

AbstractCD137 (ILA/4‐1BB), a member of tumor necrosis factor receptor superfamily, is one of the most important T cell costimulatory molecules. Interaction of this molecule with its ligand transmits a two‐way signal that activates both T lymphocyte and antigen presenting cells. The soluble form of CD137 (sCD137) reduces the activity of its membrane isoform and is associated with T lymphocyte activation‐induced cell death. Recombinant CD137‐Fc may be used to treat cancers, autoimmune disorders and viral infections. It may also be useful for management of coronavirus infection. The 1276 bp DNA sequence encoded CD137‐Fc recombinant protein was prepared and subcloned into lentiviral vector and expressed in transduced CHO‐K1 eukaryotic cells. The sodium dodecyl sulfate–polyacrylamide gel electrophoresis, Western blot analysis, and enzyme‐linked immunosorbent assay analysis results demonstrated that the expression of the 70‐kDa CD137‐Fc molecule was detectable without any degradation. This study helps to confirm previous research suggesting the use of this recombinant protein as a promising solution for the treatment of virus infections. CD137‐Fc fusion protein could also make immunotherapy more effective for some diseases. This product is widely used in novel medical treatments, including cell‐based immunotherapy such as dendritic cell, CAR T and CAR NK therapy. Its production and usage in research and treatment is noticeable also in current coronavirus disease 2019 pandemic.
Geometry dependence of excitonic couplings and the consequences for configuration‐space sampling
Authors: Schieschke Nils , Bold Beatrix M. , Dohmen Philipp M. , Wehl Daniel , Hoffmann Marvin , Dreuw Andreas , Elstner Marcus , Höfener Sebastian 
Published: May 2021

AbstractExcitonic coupling plays a key role for the understanding of excitonic energy transport (EET) in, for example, organic photovoltaics. However, the calculation of realistic systems is often beyond the applicability range of accurate wavefunction methods so that lower‐scaling semi‐empirical methods are used to model EET events. In the present work, the distance and angle dependence of excitonic couplings of dimers of selected organic molecules are evaluated for the semi‐empirical long‐range corrected density functional based tight binding (LC‐DFTB) method and spin opposite scaled second order approximate coupled cluster singles and doubles (SOS‐CC2). While semi‐empirically scaled methods can lead to slightly increased deviations for excitation energies, the excitonic couplings and their dependence on the dimer geometry are reproduced. LC‐DFTB yields a similar accuracy range as density‐functional theory (DFT) employing the ωB97X functional while the computation time is reduced by several orders of magnitude. The dependence of the exchange contributions to the excitonic couplings on the dimer geometry is analyzed assessing the calculation of Coulombic excitonic couplings from monomer local excited states only, which reduces the computational effort significantly. The present work is a necessary first step toward the simulation of excitonic energy transport using semi‐empirical methods.
Bone‐Adipose Tissue Crosstalk: Role of Adipose Tissue Derived Extracellular Vesicles in Bone Diseases
Authors: Zhang Yan , Zhang Cheng , Wang Jiasheng , Liu Hao , Wang Muyao 
Published: May 2021

AbstractBone is a metabolically active organ that undergoes constant remodeling throughout life. A failure of this process leads to pathological destructive bone diseases such as osteoporosis, rheumatoid arthritis, and osteoarthritis. Studies of the interplay between adipose tissue and bone system, have revealed that adipose tissue disorders (e.g. obesity) strongly influence the development of bone diseases. Adipokines secreted by adipose tissue play important roles in the crosstalk between bone and adipose tissue. Recently, extracellular vesicles (EVs) have been identified as a novel method of communication between different organs and have attracted increased attention in the field of bone remodeling process. Adipokines carried by EVs are known to play pivotal roles in bone remodeling processes including osteogenesis and osteoclastogenesis. In this review, we highlighted the role of adipose tissue derived EVs (EVs‐AT) in the context of bone remodeling events and focused on the characteristics of EVs‐AT and their components in the regulation of bone diseases. Moreover, we introduced the intriguing therapeutic application of EVs‐AT in different pathological destructive bone diseases and proposed future directions for research on EVs‐AT in bone diseases.
Identification of YAP1 as a novel downstream effector of the FGF2/STAT3 pathway in the pathogenesis of renal tubulointerstitial fibrosis
Authors: Li Xiaoying , Zhang Fan , Qu Lingling , Xie Ying , Ruan Yuanyuan , Guo Ziwei , Mao Yanwen , Zou Qin , Shi Mingjun , Xiao Ying , Wang Yuanyuan , Zhou Yuxia , Guo Bing 
Published: May 2021

AbstractChronic kidney disease is a global health problem and eventually develops into an end‐stage renal disease (ESRD). It is now widely believed that renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of ESRD. Renal tubular epithelial‐mesenchymal transition (EMT) is an important cause of TIF. Studies have shown that FGF2 is highly expressed in fibrotic renal tissue, although the mechanism remains unclear. We found that FGF2 can activate STAT3 and induce EMT in renal tubular epithelial cells. STAT3, an important transcription factor, was predicted by the JASPAR biological database to bind to the promoter region of YAP1. In this study, STAT3 was shown to promote the expression of the downstream target gene YAP1 through transcription, promote EMT of renal tubular epithelial cells, and mediate the occurrence of renal TIF. This study provides a theoretical basis for the involvement of the FGF2/STAT3/YAP1 signaling pathway in the process of renal interstitial fibrosis and provides a potential target for the treatment of renal fibrosis.
Electric fields regulate cellular elasticity through intracellular Ca2+ concentrations
Authors: Han Se Jik , Noh Minjoo , Jang Jihui , Lee Jun Bae , Kim Kyung Sook 
Published: May 2021

AbstractCellular elasticity is a key factor related to a broad range of physiological and pathological processes. The elasticity of a single cell has thus emerged as a potential biomarker to characterize the cellular state. Both internal and external stimuli affect cellular elasticity, and changes in elasticity can cause alterations in cellular characteristics or function. The application of electric fields (EFs) is a promising method that can be used to change cellular elasticity; however, the mechanisms underlying its effect remain unknown. Here, we demonstrate EFs‐induced elasticity changes in human dermal fibroblasts and discuss the underlying mechanism related to actin polymerization. Cellular elasticity increases after EF (50 mV/mm) stimulation, reaching a maximum at 30 min before decreasing between 30 and 120 min. The cellular elasticity under EF stimulation, regardless of stimulation time, is higher than that of the control. F‐actin regulates the elasticity of cells through gelsolin activation. We show changes in intracellular Ca2+ caused by EFs, which induced gelsolin activation and F‐actin content changes. This result demonstrates a series of processes in which external electrical stimulation conditions regulate cellular elasticity.
Physiological, psychosocial, and environmental factors in depression among autistic girls
Authors: Sharpley Christopher F. , Bitsika Vicki , McMillan Mary E. , Agnew Linda L. 
Published: May 2021

AbstractAutism Spectrum Disorder and depression are often co‐occurring in young people. However, despite the association between these two disorders, and the fact that females have a higher prevalence of depression than males in the general population, there is little reported evidence regarding the correlates of depression in young autistic females. Several physiological (age, menarche, HPA‐axis responses), psychological (social anxiety), and environmental or genetic (mothers’ depression) factors were tested for their contribution to depression severity in a sample of 53 autistic girls aged 6 yr to 17 yr. Depression scores were collected from the girls’ self‐ratings and also from the ratings their mothers gave them. Regression results indicated that girls’ social anxiety, age, and mothers’ depression were common significant contributors to both sets of depression scores, but with different effects. Autistic girls’ self‐reports of their depression were significantly associated with their HPA‐axis responses but not with their menarche status. Implications for research and clinical settings are discussed.
Utility of the inside stent as a preoperative biliary drainage method for patients with malignant perihilar biliary stricture
Authors: Nakamura Shinya , Ishii Yasutaka , Serikawa Masahiro , Tsuboi Tomofumi , Kawamura Ryota , Tsushima Ken , Hirano Tetsuro , Mori Takeshi , Uemura Kenichiro , Chayama Kazuaki 
Published: May 2021

AbstractBackground/PurposeAppropriate preoperative biliary drainage (PBD) is extremely important in patients with operable malignant perihilar biliary strictures. The aim of this study was to clarify the utility of inside stents in PBD.MethodsEighty‐one patients with malignant perihilar biliary stricture who underwent endoscopic nasobiliary drainage (ENBD) as the first PBD method were enrolled. Biliary stenting was performed in 61 patients during the study course (41 patients—inside stent implanted in the bile duct; 20 patients—conventional stent placed across the papilla of Vater). Twenty patients continued ENBD until surgery. Treatment outcomes were compared among the three groups.ResultsThe re‐intervention rate was significantly lower in the inside stent group than in the conventional stent group and ENBD group (9.8% vs 40% and 35%, P = .013 and .030, respectively), and the time to re‐intervention was also significantly longer (log‐rank: P = .004 and .041, respectively). Of the five patients in the inside stent group who underwent neoadjuvant chemotherapy, only one required re‐intervention. There was no significant difference in the incidence of postoperative complications among the three groups.ConclusionsThe inside stent may be a useful PBD method for patients with malignant perihilar biliary stricture.
Structural characteristics of coiled-coil regions in AF10-DOT1L and AF10-inhibitory peptide complex
Authors: Zhou Zhechong , Kang Sisi , Huang Zhaoxia , Zhou Ziliang , Chen Shoudeng 
Published: May 2021

AbstractThe interaction of the solo H3K79 methyltransferase DOT1-like (DOT1L) and its regulatory factor ALL1-fused gene from chromosome 10 protein (AF10) is crucial for the transcription of developmental genes such as HOXA in acute leukemia. The octapeptide motif and leucine zipper region of AF10 is responsible for binding DOT1L and catalyzing H3K79 monomethylation to demethylation. However, the characteristics of the mechanism between DOT1L and AF10 are not clear. Here, we present the crystal structures of coiled-coil regions of DOT1L-AF10 and AF10-inhibitory peptide, demonstrating the inhibitory peptide could form a compact complex with AF10 via a different recognition pattern. Furthermore, an inhibitory peptide with structure-based optimization is identified and decreases the HOXA gene expression in a human cell line. Our studies provide an innovative pharmacologic basis for therapeutic intervention in leukemia.
Gene expression analysis of subchondral bone, cartilage, and synovium in naturally occurring equine palmar/plantar osteochondral disease
Authors: Turlo Agnieszka J. , McDermott Benjamin T. , Barr Elizabeth D. , Riggs Chris M. , Boyde Alan , Pinchbeck Gina L. , Clegg Peter D. 
Published: May 2021

AbstractOsteoarthritis (OA) is a disease of the entire joint but the relationship between pathological events in various joint tissues is poorly understood. We examined concurrent changes in bone, cartilage, and synovium in a naturally occurring equine model of joint degeneration. Joints (n = 64) were grossly assessed for palmar/plantar osteochondral disease (POD) in racehorses that required euthanasia for unrelated reasons and assigned a grade of 0 (n = 34), 1 (n = 17), 2 or 3 (n = 13) using a recognized grading scheme. Synovium, cartilage, and subchondral bone were collected for histological and gene expression analysis. Relations between POD grade, cartilage histological score, and gene expression levels were examined using one‐way analysis of variance or Kruskal–Wallis test and Spearman's correlation coefficient with corrections for multiple comparisons. Cartilage histological score increased in joints with POD grade 1 (p = 0.002) and 2 or 3 (p < 0.001) compared to 0. At grade 1, expression of COL1A1, COL2A1, and MMP1 increased and BGN decreased in subchondral bone while expression of BGN and ACAN decreased in cartilage. These changes further progressed at grades 2 and 3. POD grades 2 and 3 were associated with decreased expression of osteoclast inhibitor OPG and increased markers of cartilage degeneration (MMP13, COL1A1). Expression of the vascular endothelial growth factor decreased with POD grade and negatively correlated with cartilage histological score. Synovium showed no histological or transcriptomic changes related to pathology grade. Cartilage degeneration in POD is likely to be secondary to remodeling of the subchondral bone. Limited activation of proinflammatory and catabolic genes and moderate synovial pathology suggests distinct molecular phenotype of POD compared with OA.
Shifting cultivation, soil degradation, and agricultural land‐use planning in the northeastern hill region of India using geo‐spatial techniques
Authors: Ray Prasenjit , Chattaraj Sudipta , Bandyopadhyay Siladitya , Jena Roomesh K. , Singh Surendra K. , Ray Sanjay K. 
Published: May 2021

AbstractShifting cultivation is widely practiced in the northeastern hill (NEH) region of India. It is known that the destruction of natural forests and its conversion to cropland leads to soil resource degradation. The impacts on soil due to jhuming (jhum practice followed in shifting cultivation) have not been studied adequately. Also, study of alternatives to jhum land use is lacking. In our study, a soil resource inventory of jhum lands was generated for a part of the Purvanchal Ranges of Eastern Himalaya, India to ascertain the nature of soil resource degradation due to jhuming using geo‐spatial techniques. High‐resolution IRS P6 LISS‐IV and stereo‐pair CARTOSAT‐I satellite images along with digital elevation model data were used to map soil resources of jhum lands through a detailed soil survey. Typical pedons were also studied in the native forest adjacent to the jhum lands. Further, land suitability evaluation of the identified soil series for crop growth was carried out to propose alternative land‐use models for jhum lands distributed over different landforms. Results indicated that soils of jhum lands were organically degraded and followed regressive pedogenesis, whereas forest soils followed progressive pedogenesis, particularly on high (650–1250 masl) and medium hills (250–650 masl). Alternaive land‐use models with the inclusion of upland rice and without the inclusion of rice have been proposed. Results of the investigation should be useful for policy makers to seeking make the best use of the land resources under jhum cultivation.
The advanced practitioners’ perspective. Exploring the decision‐making process between musculoskeletal advanced practitioners and their patients: An interpretive phenomenological study
Authors: Thompson Jonathan , Gabriel Lynne , Yoward Samantha , Dawson Pamela 
Published: May 2021

AbstractIntroductionAdvanced practice roles for allied health professionals continue to expand and provide key services within pathways of care for patients with musculoskeletal conditions. Despite the extensive utilisation of these roles and previously reported high patient satisfaction, little is understood about how these practitioners interact with their patients and the factors that influence decision‐making conversations.StudyA qualitative study utilised Interpretive Phenomenological Analysis (IPA) to explore the decision‐making process occurring between Advanced Practitioners (APs) and their patients in a musculoskeletal service. AP data were collected through focus groups and analysed using IPA methodology.ConclusionsAdvanced practice decision‐making is a complex process and APs exhibit a range of styles, from paternalistic to shared decision‐making. APs may have a personal preference, but exhibit the ability to flex between styles in consultations. Multiple themes emerged from the data that influenced the decision‐making process, including AP staff understanding the importance of patient expectations and the complex factors that influence patient interactions. It is important that clinicians have an awareness of the multiple factors that contribute to the decision‐making process.
Quantitative platform for accurate and reproducible assessment of transverse (T2) relaxation time
Authors: Radunsky Dvir , Stern Neta , Nassar Jannette , Tsarfaty Galia , Blumenfeld‐Katzir Tamar , Ben‐Eliezer Noam 
Published: May 2021

MRI's transverse relaxation time (T2) is sensitive to tissues' composition and pathological state. While variations in T2 values can be used as clinical biomarkers, it is challenging to quantify this parameter in vivo due to the complexity of the MRI signal model, differences in protocol implementations, and hardware imperfections. Herein, we provide a detailed analysis of the echo modulation curve (EMC) platform, offering accurate and reproducible mapping of T2 values, from 2D multi‐slice multi‐echo spin‐echo (MESE) protocols.Computer simulations of the full Bloch equations are used to generate an advanced signal model, which accounts for stimulated echoes and transmit field (B1+) inhomogeneities. In addition to quantifying T2 values, the EMC platform also provides proton density (PD) maps, and fat‐water fraction maps. The algorithm's accuracy, reproducibility, and insensitivity to T1 values are validated on a phantom constructed by the National Institute of Standards and Technology and on in vivo human brains.EMC‐derived T2 maps show excellent agreement with ground truth values for both in vitro and in vivo models. Quantitative values are accurate and stable across scan settings and for the physiological range of T2 values, while showing robustness to main field (B0) inhomogeneities, to variations in T1 relaxation time, and to magnetization transfer. Extension of the algorithm to two‐component fitting yields accurate fat and water T2 maps along with their relative fractions, similar to a reference three‐point Dixon technique.Overall, the EMC platform allows to generate accurate and stable T2 maps, with a full brain coverage using a standard MESE protocol and at feasible scan times. The utility of EMC‐based T2 maps was demonstrated on several clinical applications, showing robustness to variations in other magnetic properties. The algorithm is available online as a full stand‐alone package, including an intuitive graphical user interface.
Biological changes in the pregnancy‐postpartum period and subsequent cardiometabolic risk—UPSIDE MOMS: A research protocol
Authors: Groth Susan W. , Fernandez I. Diana , Block Robert C. , Thurston Sally W. , Wong Eunyoung , Brunner Jessica , Mayo Nicole , Kapula Ntemena , Yu Yang , Meng Ying , Yeh Kuan‐Lin , Kinkade Carolyn W. , Thornburg Loralei L. , O'Connor Thomas G. , Barrett Emily S. 
Published: May 2021

AbstractMultiple physiological changes occur in pregnancy as a woman's body adapts to support the growing fetus. These pregnancy‐induced changes are essential for fetal growth, but the extent to which they reverse after pregnancy remains in question. For some women, physiological changes persist after pregnancy and may increase long‐term cardiometabolic disease risk. The National Institutes of Health‐funded study described in this protocol addresses a scientific gap by characterizing weight and biological changes during pregnancy and an extended postpartum period in relation to cardiometabolic risk. We use a longitudinal repeated measures design to prospectively examine maternal health from early pregnancy until 3 years postpartum. The aims are: (1) identify maternal weight profiles in the pregnancy‐postpartum period that predict adverse cardiometabolic risk profiles three years postpartum; (2) describe immune, endocrine, and metabolic biomarker profiles in the pregnancy‐postpartum period, and determine their associations with cardiometabolic risk; and (3) determine how modifiable postpartum health behaviors (diet, physical activity, breastfeeding, sleep, stress) (a) predict weight and cardiometabolic risk in the postpartum period; and (b) moderate associations between postpartum weight retention and downstream cardiometabolic risk. The proposed sample is 250 women. This study of mothers is conducted in conjunction with the Understanding Pregnancy Signals and Infant Development study, which examines child health outcomes. Biological and behavioral data are collected in each trimester and at 6, 12, 24, and 36 months postpartum. Findings will inform targeted health strategies that promote health and reduce cardiometabolic risk in childbearing women.
Caregiver's difficulty paying child's healthcare bills and bullying victimization of adolescents with physical disabilities
Authors: Hong Jun Sung , Choi Mi‐Jin , Kim Isak , Algood Carl L. , Espelage Dorothy L. , Rose Chad A. 
Published: May 2021

AbstractGuided by the ecological systems perspective, the objective of the study was to examine whether caregivers' difficulty paying their child's health‐care bills is associated with bullying victimization directly and indirectly through the mediating mechanisms of caregivers' frustration, adolescents' internalizing problems, and social difficulty focusing on adolescents with physical disabilities. The 2019 National Survey of Children's Health dataset, which collected data on adolescents' and caregivers' demographic characteristics and health and well‐being, was used. The study sample consisted of 368 caregivers of adolescents, 12–17 years of age with physical disabilities. No direct association between caregivers' difficulty paying their child's health‐care bills and bullying victimization was found. However, caregivers' frustration and adolescents' internalizing problems were shown to have an indirect association with bullying victimization, which was mediated by difficulty making friends. In addition, adolescents' difficulty making friends was positively associated with bullying victimization. Practitioners working with adolescents with physical disabilities are encouraged to foster collaborative processes across various ecological systems of the adolescent and family to address caregivers' frustration and promote positive social and emotional development of the adolescent with physical disabilities, which can decrease their risk of bullying victimization.