bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes mellitus among adult survivors of childhood acute lymphoblastic leukemia: A report from the St. Jude Lifetime Cohort Study
Authors: Williams Hannah E. , Howell Carrie R. , Chemaitilly Wassim , Wilson Carmen L. , Karol Seth E. , Nolan Vikki G. , Smeltzer Matthew P. , Green Daniel M. , Ehrhardt Matthew J. , Mulrooney Daniel A. , Pui Ching‐Hon , Hudson Melissa M. , Robison Leslie L. , Ness Kirsten K. 
Published: November 2019

BackgroundGreater than one‐half of children who are treated for acute lymphoblastic leukemia (ALL) develop ≥1 treatment‐related medical conditions in their lifetime, many of which are known risk factors for diabetes mellitus. In the current study, the authors evaluated the prevalence and risk factors of diabetes mellitus among clinically assessed adult survivors of childhood ALLMethodsThe authors performed a retrospective evaluation of data from survivors of ALL and community controls who were enrolled in the St. Jude Lifetime Cohort Study between October 1, 2007, and June 30, 2016. Participants were adults with ≥10 years of survival of childhood ALL and community controls who completed clinical and laboratory evaluations. Data for the current analysis were abstracted from medical records. Exposures evaluated herein included chemotherapy and radiation exposures and medical history, including drug‐induced diabetes mellitus.ResultsOf 1360 eligible adults who were ≥10‐year survivors of childhood ALL, a total of 1044 completed the evaluations; these individuals had a mean age of 33.97±9.14 years and 50.86% were male. The 368 controls, 45.65% of whom were male, had a mean age of 35.33±10.21 years. Type 2 diabetes mellitus (T2DM) was found in approximately 7.47% of survivors and 3.80% of controls (odds ratio [OR], 2.07; 95% CI, 1.11‐3.87). In adjusted models, among survivors, older age (OR, 1.05 for each additional year; 95% CI, 1.02‐1.08), body mass index ≥30 kg/m2 (OR, 7.40; 95% CI, 2.61‐20.97), and drug‐induced diabetes mellitus occurring during ALL therapy (OR, 4.67; 95% CI, 2.53‐8.61) were found to be associated with T2DM.ConclusionsAdult survivors of childhood ALL are at an increased risk of T2DM. Adult survivors of childhood ALL who are of older age, with an overweight or obese body mass index, and/or who developed drug‐induced diabetes mellitus during treatment should be closely monitored for T2DM during long‐term follow‐up.
Rapid Identification of Protein‐Protein Interactions in Plants
Authors: Zhang Youjun , Natale Roberto , Domingues Adilson Pereira , Toleco Mitchell Rey , Siemiatkowska Beata , Fàbregas Norma , Fernie Alisdair R. 
Published: November 2019

AbstractEnzyme‐enzyme interactions can be discovered by affinity purification mass spectrometry (AP‐MS) under in vivo conditions. Tagged enzymes can either be transiently transformed into plant leaves or stably transformed into plant cells prior to AP‐MS. The success of AP‐MS depends on the levels and stability of the bait protein, the stability of the protein‐protein interactions, and the efficiency of trypsin digestion and recovery of tryptic peptides for MS analysis. Unlike in‐gel‐digestion AP‐MS, in which the gel is cut into pieces for several independent trypsin digestions, we uses a proteomics‐based in‐solution digestion method to directly digest the proteins on the beads following affinity purification. Thus, a single replicate within an AP‐MS experiment constitutes a single sample for LC‐MS measurement. In subsequent data analysis, normalized signal intensities can be processed to determine fold‐change abundance (FC‐A) scores by use of the SAINT algorithm embedded within the CRAPome software. Following analysis of co‐sublocalization of “bait” and “prey,” we suggest considering only the protein pairs for which the intensities were more than 2% compared with the bait, corresponding to FC‐A values of at least four within‐biological replicates, which we recommend as minimum. If the procedure is faithfully followed, experimental assessment of enzyme‐enzyme interactions can be carried out in Arabidopsis within 3 weeks (transient expression) or 5 weeks (stable expression). © 2019 The Authors.Basic Protocol 1: Gene cloning to the destination vectorsAlternate Protocol: In‐Fusion or Gibson gene cloning protocolBasic Protocol 2: Transformation of baits into the plant cell culture or plant leafBasic Protocol 3: Affinity purification of protein complexesBasic Protocol 4: On‐bead trypsin/LysC digestion and C18 column peptide desalting and concentrationBasic Protocol 5: Data analysis and quality control
Geography, seasonality, and host‐associated population structure influence the fecal microbiome of a genetically depauparate Arctic mammal
Authors: Bird Samantha , Prewer Erin , Kutz Susan , Leclerc Lisa‐Marie , Vilaça Sibelle T. , Kyle Christopher J. 
Published: November 2019

AbstractThe Canadian Arctic is an extreme environment with low floral and faunal diversity characterized by major seasonal shifts in temperature, moisture, and daylight. Muskoxen (Ovibos moschatus) are one of few large herbivores able to survive this harsh environment. Microbiome research of the gastrointestinal tract may hold clues as to how muskoxen exist in the Arctic, but also how this species may respond to rapid environmental changes. In this study, we investigated the effects of season (spring/summer/winter), year (2007–2016), and host genetic structure on population‐level microbiome variation in muskoxen from the Canadian Arctic. We utilized 16S rRNA gene sequencing to characterize the fecal microbial communities of 78 male muskoxen encompassing two population genetic clusters. These clusters are defined by Arctic Mainland and Island populations, including the following: (a) two mainland sampling locations of the Northwest Territories and Nunavut and (b) four locations of Victoria Island. Between these geographic populations, we found that differences in the microbiome reflected host‐associated genetic cluster with evidence of migration. Within populations, seasonality influenced bacterial diversity with no significant differences between years of sampling. We found evidence of pathogenic bacteria, with significantly higher presence in mainland samples. Our findings demonstrate the effects of seasonality and the role of host population‐level structure in driving fecal microbiome differences in a large Arctic mammal.
Guidance for Design and Endpoints of Clinical Trials in Chronic Hepatitis B—Report From the 2019 EASL‐AASLD HBV Treatment Endpoints Conference
Authors: Cornberg Markus , Lok Anna Suk‐Fong , Terrault Norah A. , Zoulim Fabien ,   the 2019 EASL‐AASLD HBV Treatment Endpoints Conference Faculty
Published: November 2019

Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic hepatitis B virus (HBV) treatment endpoints to guide clinical trials aiming to “cure” HBV. Agreement among the conference participants was reached on some key points. “Functional” but not sterilising cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post‐treatment. The primary endpoint of phase III trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity for the prediction of sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg‐positive or negative chronic hepatitis, who are treatment‐naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with an increase in bilirubin or international normalised ratio should prompt temporary or permanent cessation of an investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase III trials for HDV coinfection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalisation of alanine aminotransferase is considered an intermediate goal. In conclusion, regarding HBV “functional cure”, the primary goal is sustained HBsAg loss with undetectable HBV DNA after completion of treatment and the intermediate goal is sustained undetectable HBV DNA without HBsAg loss after stopping treatment.
Inactivation of ATRX in forebrain excitatory neurons affects hippocampal synaptic plasticity
Authors: Gugustea Radu , Tamming Renee J. , Martin‐Kenny Nicole , Bérubé Nathalie G. , Leung L. Stan 
Published: November 2019

Abstractα‐Thalassemia X‐linked intellectual disability (ATR‐X) syndrome is a neurodevelopmental disorder caused by mutations in the ATRX gene that encodes a SNF2‐type chromatin‐remodeling protein. The ATRX protein regulates chromatin structure and gene expression in the developing mouse brain and early inactivation leads to DNA replication stress, extensive cell death, and microcephaly. However, the outcome of Atrx loss of function postnatally in neurons is less well understood. We recently reported that conditional inactivation of Atrx in postnatal forebrain excitatory neurons (ATRX‐cKO) causes deficits in long‐term hippocampus‐dependent spatial memory. Thus, we hypothesized that ATRX‐cKO mice will display impaired hippocampal synaptic transmission and plasticity. In the present study, evoked field potentials and current source density analysis were recorded from a multichannel electrode in male, urethane‐anesthetized mice. Three major excitatory synapses, the Schaffer collaterals to basal dendrites and proximal apical dendrites, and the temporoammonic path to distal apical dendrites on hippocampal CA1 pyramidal cells were assessed by their baseline synaptic transmission, including paired‐pulse facilitation (PPF) at 50‐ms interpulse interval, and by their long‐term potentiation (LTP) induced by theta‐frequency burst stimulation. Baseline single‐pulse excitatory response at each synapse did not differ between ATRX‐cKO and control mice, but baseline PPF was reduced at the CA1 basal dendritic synapse in ATRX‐cKO mice. While basal dendritic LTP of the first‐pulse excitatory response was not affected in ATRX‐cKO mice, proximal and distal apical dendritic LTP were marginally and significantly reduced, respectively. These results suggest that ATRX is required in excitatory neurons of the forebrain to achieve normal hippocampal LTP and PPF at the CA1 apical and basal dendritic synapses, respectively. Such alterations in hippocampal synaptic transmission and plasticity could explain the long‐term spatial memory deficits in ATRX‐cKO mice and provide insight into the physiological mechanisms underlying intellectual disability in ATR‐X syndrome patients.
Assessing perceived quality of primary care under hospital‐township health centre integration: A cross‐sectional study in China
Authors: Yuan Shasha , Wang Fang , Zhao Yan , Liu Yun 
Published: November 2019

SummarySince the new round of health care reform in 2009, the vertical integration of hospitals and primary health institutions has become widely implemented in China as an efficient method for improving quality of primary care. This study aimed to answer the following questions: (a) What is the perceived quality of township health centres (THCs) under integration? (B) What differences could be observed among the three typical integration models, namely, private hospital‐THC integration, public hospital‐THC integration, and loose collaboration? Two rounds of cross‐sectional surveys were conducted from November 2016 to June 2018. The Chinese version of the Primary Care Assessment Tool was used to evaluate perceived quality of sample THCs, and 1118 adult patients were interviewed in total. Multiple linear regressions were employed to compare the quality scores between two survey rounds and among different integration models after controlling for potential confounders. The results revealed that the quality of care significantly improved under private hospital‐THC integration as observed by comparing two survey rounds, while no change or slight changes were observed in the other two models. The difference observed among the three models was that the perceived quality of THCs integrated with private hospitals was worse than that of THCs integrated with public hospitals and THCs under loose collaboration, while no significant difference was observed between public hospital‐THC integration and loose collaboration. Increased attention should be given to highlighting the tight integration between hospitals and THCs and the different roles played by private and public hospitals in the current reform.
Dynamic correlation and volatility spillovers across Chinese stock and commodity futures markets
Authors: Kang Sang Hoon , Yoon Seong‐Min 
Published: November 2019

AbstractThis paper examines the return links and volatility transmission between Chinese stock and commodity futures markets and draws implications for portfolio risk management. To these ends, we consider three vector autoregression‐multivariate generalized autoregressive conditional heteroskedasticity‐class models with which to model volatilities and conditional correlations between Chinese stock and three commodity futures markets. Our empirical results reveal evidence of return linkage and volatility transmission between the Chinese stock and commodity futures markets. We also analyse optimal portfolio weights and hedging ratios between s1tock–commodity pairs. Finally, we assess implications for mixed commodity–stock portfolios and find strong evidence of hedging effectiveness and downside risk reductions.
Van der Waals magnets: Wonder building blocks for two‐dimensional spintronics?
Authors: Zhang Wen , Wong Ping Kwan Johnny , Zhu Rui , Wee Andrew T. S. 
Published: November 2019

AbstractThe unprecedented realization of two‐dimensional (2D) van der Waals magnets excitingly extends the synergy between spintronics and 2D materials, started with graphene over the last decade. This article reviews the recent milestones in the development of 2D magnets and its derived heterostructures. In particular, a number of critical challenges centered around the scalability, ambient stability and Curie temperature of these atomically thin magnets are discussed. This mini‐review also provides an outlook on what the future might hold for this integrated field of 2D spintronics, and assesses its potential in postsilicon electronics.
Cholesterol grafted cationic lipopolymers: Potential siRNA carriers for selective chronic myeloid leukemia therapy
Authors: Remant KC , Thapa Bindu , Valencia‐Serna Juliana , Domun Suraj S. , Dimitroff Cailean , Jiang Xiaoyan , Uludağ Hasan 
Published: November 2019

AbstractSynthetic siRNA technology has emerged as a promising approach for molecular therapy of cancer but, despite its potential for post‐transcriptional gene silencing, there is an urgent need to develop efficient delivery systems particularly for difficult‐to‐transfect, anchorage‐independent cells. In this study, we designed highly hydrophobic cationic lipopolymers by grafting cholesterol (Chol) onto low‐molecular weight (0.6, 1.2, and 2.0 kDa) polyethylenimines (PEIs) to enable specific siRNA therapy to chronic myeloid leukemia (CML) cells. The siRNA binding by PEI‐Chol led to nano‐sized (100–200 nm diameter) polyplexes with enhanced ζ‐potential (+20 to +35 mV) and ability to protect the loaded siRNA completely in fresh serum. The siRNA delivery to CML (K562) cells was proportional to degree of substitution and, unexpectedly, inversely proportional to molecular size of the polymeric backbone. Chol grafting with as little as ~1.0 Chol/PEI on 0.6 and 1.2 kDa PEIs enabled silencing of the reporter Green Fluorescent Protein gene as well as the endogenous BCR‐Abl oncogene in K562 cells. The PEI‐Chol mediated delivery of siRNAs specific for BCR‐Abl and KSP genes significantly arrested the growth the cells which was significantly reflected in colony formation potency of K562 cells. BCR‐Able siRNA mediated therapeutic efficacy was also observed in significantly increased caspase activity and apoptosis of K562 cells. Thus, Chol‐grafted low‐molecular weight PEIs appear to be unique siRNA carriers to realize the molecular therapy in CML cells.
The characteristic regulation of gene expression Lbp and Sod3 in peri‐implant connective tissue of rats
Authors: Kobayashi Takafumi , Sasaki Hodaka , Asami Yosuke , Mori Gentaro , Yoshinari Masao , Yajima Yasutomo 
Published: November 2019

AbstractThe aim of this study was to investigate the characteristic gene expression profile and localization of peri‐implant connective tissue (PICT) compared with those of periodontal connective tissue (PCT) and oral mucosal connective tissue (OMCT). Upper first molar of 5‐week‐old rats were extracted and titanium implant were placed for PICT group. PCT and OMCT were used as control. Laser microdissected connective tissue at 4 weeks used for microarray analysis. The expression and localization of selected genes were confirmed by quantitative real‐time PCR (qRT‐PCR) and immunohistochemistry. Approximately, 1000 genes of upregulated and downregulated in PICT compared with PCT and OMCT were recognized. Based on the results of microarray analysis and qRT‐PCR were demonstrated lipopolysaccharide binding protein (Lbp) as a specific upregulated gene and superoxide dismutase 3 (Sod3) as a specific downregulated gene in PICT. Immunoreaction of LBP and F4/80 as macrophage marker localized to subepithelial and implant facing connective tissue in PICT. SOD3 expression was not observed in PICT, reactive oxygen species, a target of superoxide dismutase, was strongly and locally expressed in all three tissues. Our data suggested that the upregulation of Lbp and downregulation of Sod3 are as characteristic gene expression pattern in PICT.
Melatonin: A promising agent targeting leukemia
Authors: Shafabakhsh Rana , Mirzaei Hamed , Asemi Zatollah 
Published: November 2019

AbstractLeukemia or cancer of blood is a well‐known cancer, which affects a range of people from newborns to the very old. It is a public health problem throughout the world. By way of treatment, due to the lack of specific anticancer therapies, common treatments of leukemia lead to severe side effects. Nonspecific anticancer drugs result in inhibition of normal cell growth and thereby their necrosis. Moreover, drug resistance is an additional problem, which stands in the way of leukemia treatment. Thus, finding new treatments for leukemia is essential. Melatonin, as a natural product, has been shown to be effective in a wide variety of diseases such as coronary heart disease, schizophrenia, chronic pain, and Alzheimer's disease. In addition, melatonin levels have been observed to be altered in different cancers, such as breast cancer, colorectal cancer endometrial cancer, and hematopoetical cancers. Anticancer features of melatonin such as pro‐oxidation, apoptosis induction, antiangiogenesis property and metastasis and invasion inhibition suggest that this natural compound can be used as a potential agent in novel therapeutic strategies for cancers. Also, it has been reported that melatonin has positive and protective effects on different physiological reactions and in normal bone marrow cells suggesting effectiveness in leukemia therapy. Thus, the aim of our paper was to depict and summarize the main molecular targets of melatonin on leukemia models.
BMP2 variants in the risk of ankylosing spondylitis
Authors: Qi Dengbin , Tian Xiaodong , Wang Yan , Zheng Guoquan , Zhang Xuesong 
Published: November 2019

AbstractThe purpose of the study was to explore the genetic effects of bone morphogenetic protein (BMP2) polymorphisms on the susceptibility to ankylosing spondylitis (AS) in Chinese Han population. The case‐control study included 120 AS cases and 110 healthy controls. Hardy‐Weinberg equilibrium test was performed in control group. BMP2 rs235768 and rs3178250 polymorphisms were analyzed by polymerase chain reaction and direct sequencing. Additionally, the χ2 test was used to estimate association strength between BMP2 genetic polymorphisms and AS susceptibility, and the results were assessed via odds ratio (OR) with the corresponding 95% confidence interval (95%CI). Results adjustment was performed using logistic regression analysis. AA, AT, TT genotype and A, T allele frequencies of BMP2 rs235768 polymorphism presented no significant differences between case and control groups (P > .05 for all). TC genotype of rs3178250 polymorphism showed significantly higher in case group than that in control group (P = .048). After adjusting, TC genotype was a risk factor for AS (OR = 2.095; 95%CI = 1.086‐4.038; P = .027). BMP2 rs3178250 polymorphism may increase individual susceptibility to AS in Chinese Han population.
Synthesis, characterization, and in vitro toxicity evaluation of upconversion luminescence NaLuF4:Yb3+/Tm3+ nanoparticles suitable for medical applications
Authors: Asadi Mohammad , Ghahari Mehdi , Hassanzadeh‐Tabrizi Seyed A. , Arabi Amir M. , Nasiri Rozita 
Published: November 2019

AbstractSynthesis, characterization, and in vitro toxicity evaluation of upconversion luminescence NaLuF4:Yb3+/Tm3+ nanoparticles (UCLNPs) are reported in the current study. Initially, the synthesized lanthanide trifluoroacetate (Ln(OOCCF3)3) precursor was used to fabricate NaLuF4 nanoparticles doped with Yb3+ and Tm3+ metal ions. The nanoparticles were coated with calcium carbonate (CaCO3) after removing the hydrophobic species on them to enhance their biocompatibility. The in vitro methylthiazolyldiphenyl‐tetrazoliumbromide (MTT) test was used to evaluate the toxicity of synthesized NaLuF4:Yb3+/Tm3+ nanoparticles (NLF‐5) on L929 mouse fibroblast cell lines. The transmission electron microscopy image showed that the particle size of NaLuF4:Yb3+/Tm3+ was 32 nm. The synthesized NLF‐5 nanoparticles have both α‐cubic and β‐hexagonal crystalline structures that provided a superb near‐infrared‐to‐near‐infrared upconversion luminescence signal when excited at 980 nm. MTT test results show that the death of L929 fibroblast cells was observed only at concentrations above 250 μg/mL of NaLuF4:Yb3+/Tm3+ nanoparticles. In addition, with an increase in patrol time of 24, 48, and 72 hr, cell toxicity increased significantly, while the coated nanoparticles did not have any toxic effects. The synthesized nanoparticles could be used as a suitable material for medical applications due to their small particle size, high photoluminescence emission intensity, and low toxicity.