bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjustment of azathioprine dose should be based on a lower 6‐TGN target level to avoid leucopenia in NUDT15 intermediate metabolisers
Authors: Kang Ben , Kim Tae Jun , Choi Jaeyoung , Baek Sun‐Young , Ahn Soohyun , Choi Rihwa , Lee Soo‐Youn , Choe Yon Ho 
Published: June 2020

SummaryBackgroundThe association between NUDT15 polymorphisms and thiopurine‐induced leucopenia is well known.AimTo investigate the association between NUDT15 polymorphisms and time‐to‐leucopenia in paediatric patients with inflammatory bowel disease (IBD) receiving azathioprine and to determine the relationship between NUDT15 polymorphisms and 6‐thioguanine nucleotide (6‐TGN) levels.MethodsThis retrospective observational study included Korean paediatric patients with IBD who were treated with azathioprine and underwent NUDT15 and TPMT genotyping. Azathioprine doses were adjusted by regular thiopurine metabolite monitoring. Factors associated with time‐to‐leucopenia and the relationship between NUDT15 polymorphisms and 6‐TGN levels were analysed.ResultsAmong the 167 patients included, leucopenia was observed in 16% (19/119), 44% (20/45) and 100% (3/3) of the NUDT15 normal, intermediate and poor metabolisers respectively (P < 0.001). NUDT15 polymorphism was significantly associated with time‐to‐leucopenia (HR = 5.26, 95% CI = 2.74‐10.09, P < 0.001). There was a positive association between 6‐TGN levels and leucopenia among the NUDT15 intermediate/TPMT normal metabolisers (median 361.3 vs 263.8 pmol/8 × 108 RBC, P = 0.013). The most accurate 6‐TGN cut‐off level associated with leucopenia was 308.2 pmol/8 × 108 RBC (AUC = 0.742, 95% CI = 0.569‐0.915, sensitivity 80.0%, specificity 72.7%, P < 0.001) in this subgroup. When the specificity was set to <15%, the 6‐TGN cut‐off level was 167.1 pmol/8 × 108 RBC (sensitivity 93.3%, specificity 13.6%).ConclusionsNUDT15 polymorphisms were associated with time‐to‐leucopenia during azathioprine treatment in Korean paediatric patients with IBD. In order to reduce the development of thiopurine‐induced leucopenia (<15%) in NUDT15 intermediate metabolisers, adjustment of azathioprine doses should be based on a lower 6‐TGN target level (<167.1 pmol/8 × 108 RBC).
Clinical value of next‐generation sequencing compared to cytogenetics in patients with suspected myelodysplastic syndrome
Authors: Kawata Eri , Lazo‐Langner Alejandro , Xenocostas Anargyros , Hsia Cyrus C. , Howson‐Jan Kang , Deotare Uday , Saini Lalit , Yang Ping , Broadbent Robert , Levy Michael , Howlett Christopher , Stuart Alan , Kerkhof Jennifer , Santos Stephanie , Lin Hanxin , Sadikovic Bekim , Chin‐Yee Ian 
Published: June 2020

SummaryNext‐generation sequencing (NGS) increasingly influences diagnosis, prognosis and management of myelodysplastic syndrome (MDS). In addition to marrow morphology and flow cytometry, our institution performs cytogenetics (CG) and NGS‐based testing routinely in patients with suspected MDS. We evaluated the relative value of NGS in the assessment of patients with suspected MDS. We initially compared the diagnostic and prognostic information derived from CG and NGS in 134 patients. NGS enhanced the diagnostic yield compared to CG for clonal myeloid disorders (sensitivity 77% vs. 42·2%; specificity 90·2% vs. 78%; positive predictive value 92·8% vs. 76%; and negative predictive value 70·8% vs. 45·5%). The identification of poor prognosis mutations by NGS altered risk category in 27/39 (69·2%) patients with MDS with good/intermediate risk CG. Subsequently, we prospectively evaluated 70 patients with suspected MDS using an ‘NGS‐first approach’ with CG restricted to samples with morphological abnormalities. We rarely identified mutations or CG abnormalities in patients without dysplastic features. NGS has a superior diagnostic performance compared to CG in patients with suspected MDS. We estimate that by using an ‘NGS‐first approach’ we could reduce karyotyping by approximately 30%.
Pharmaco‐genetic inhibition of pyramidal neurons retards hippocampal kindling‐induced epileptogenesis
Authors: Chen Li‐Ying , Liang Jiao , Fei Fan , Ruan Ye‐Ping , Cheng He‐Ming , Wang Yi , Chen Zhong , Xu Ceng‐Lin 
Published: June 2020

AbstractAimsPharmaco‐genetics emerges as a new promising approach for epileptic seizures. Whether it can modulate epileptogenesis is still unknown.MethodsHere, parvalbumin neurons and pyramidal neurons of the seizure focus were transfected with engineered excitatory Gq‐coupled human muscarinic receptor hM3Dq and engineered inhibitory Gi‐coupled human muscarinic receptor hM4Di, respectively. And their therapeutic value in mouse hippocampal kindling‐induced epileptogenesis was tested.ResultsPharmaco‐genetic activating parvalbumin neurons limitedly retarded the progression of behavioral seizure stage and afterdischarge duration (ADD) during epileptogenesis induced by kindling. Activating parvalbumin neurons delayed seizure development only in the early stage, but accelerated it in late stages. On the contrary, pharmaco‐genetic inhibiting pyramidal neurons robustly retarded the progression of seizure stages and ADDs, which greatly delayed seizure development in both early and late stages. Although both pharmaco‐genetic therapeutics efficiently alleviated the severity of acute kindling‐induced seizures, pharmaco‐genetic inhibiting pyramidal neurons were able to reverse the enhanced synaptic plasticity during epileptogenesis, compared with that of pharmaco‐genetic activating parvalbumin neurons.ConclusionOur results demonstrated that pharmaco‐genetic inhibiting pyramidal neurons retard hippocampal kindling‐induced epileptogenesis and reverse the enhanced synaptic plasticity during epileptogenesis, compared with that of pharmaco‐genetic activating parvalbumin neurons. It suggests that pharmaco‐genetics targeting pyramidal neurons may be a promising treatment for epileptogenesis.
RNA processing genes characterize RNA splicing and further stratify colorectal cancer
Authors: Lu Xiaofan , Zhou Yujie , Meng Jialin , Jiang Liyun , Gao Jun , Cheng Yu , Yan Hangyu , Wang Yang , Zhang Bing , Li Xiaobo , Yan Fangrong 
Published: June 2020

AbstractObjectivesDue to the limited evaluation of the prognostic value of RNA processing genes (RPGs), which are regulators of alternative splicing events (ASEs) that have been shown to be associated with tumour progression, this study sought to determine whether colorectal cancer (CRC) could be further stratified based on the expression pattern of RPGs.Materials and MethodsThe gene expression profiles of CRCs were collected from TCGA (training set) and three external validation cohorts, representing 1060 cases totally. Cox regression with least absolute shrinkage and selection operator (LASSO) penalty was used to develop an RNA processing gene index (RPGI) risk score. Kaplan‐Meier curves, multivariate Cox regression and restricted mean survival (RMS) analyses were harnessed to evaluate the prognostic value of the RPGI.ResultsA 22‐gene RPGI signature was developed, and its risk score served as a strong independent prognostic factor across all data sets when adjusted for major clinical variables. Moreover, ASEs for certain genes, such as FGFR1 and the RAS oncogene family, were significantly correlated with RPGI. Expression levels of genes involved in splicing‐ and tumour‐associated pathways were significantly correlated with RPGI score. Furthermore, a combination of RPGI with age and tumour stage resulted in significantly improved prognostic accuracy.ConclusionsOur findings highlighted the prognostic value of RPGs for risk stratification of CRC patients and provide insights into specific ASEs associated with the development of CRC.
Exopolysaccharide from Cryptococcus heimaeyensis S20 induces autophagic cell death in non‐small cell lung cancer cells via ROS/p38 and ROS/ERK signalling
Authors: Hao Yao , Huang Yao , Chen Jingyi , Li Jiadai , Yuan Yuncong , Wang Mingzhen , Han Lingling , Xin Xiu , Wang Hailong , Lin Danqing , Peng Fang , Yu Fang , Zheng Congyi , Shen Chao 
Published: June 2020

AbstractObjectivesCryptococcus heimaeyensis S20 is found in Antarctica and can produce exopolysaccharides (CHEPS). Here, we explore the anti‐tumour effects of CHEPS on non‐small cell lung cancer (NSCLC).Materials and methodsCell viability was assessed by CCK8 and colony formation assays. Flow cytometry was used to analyse the cell cycle, cell apoptosis and reactive oxygen species (ROS). Cell autophagy was detected by EGFP‐LC3 puncta assay, Lyso‐Tracker Red staining and transmission electron microscopy. mRNA and protein levels were analysed by qRT‐PCR and Western blot. Related mechanisms were confirmed using appropriate inhibitors or shRNA. In vitro results were further confirmed by a tumour xenograft study.ResultsCHEPS inhibited the proliferation of NSCLC cells by inducing S‐ and G2/M‐phase arrest and autophagic cell death, but not apoptosis. CHEPS was less toxic to normal human embryonic lung fibroblasts. CHEPS activated the MAPK pathway in NSCLC cells, and p38 and ERK promoted CHEPS‐induced cell death. Further studies showed that p38 and ERK promoted CHEPS‐induced NSCLC cell autophagy and ERK promoted CHEPS‐induced S‐ and G2/M‐phase arrest. ROS were induced by CHEPS. A ROS scavenger attenuated CHEPS‐induced p38 and ERK activation, autophagy and cell death. Finally, CHEPS reduced orthotopic lung tumour growth without organ‐related toxicity. CHEPS also induced ROS, activated p38 and ERK, and triggered autophagy in vivo.ConclusionsCHEPS induces autophagic cell death and S‐ and G2/M‐phase arrest in NSCLC cells via ROS/p38 and ROS/ERK signalling.
Chrysophanic acid shifts the differentiation tendency of BMSCs to prevent alcohol‐induced osteonecrosis of the femoral head
Authors: Yu Hongping , Liu Pei , Zhu Daoyu , Yin Junhui , Yang Qianhao , Huang Yigang , Chen Yixuan , Zhang Changqing , Gao Youshui 
Published: June 2020

AbstractObjectivesOsteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol‐induced ONFH.Materials and MethodsThe effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol‐induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods.ResultsIn vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti‐osteogenesis of alcohol partly via PI3K/AKT pathway and retard the promotion of alcohol‐induced adipogenesis via AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol‐induced ONFH and substantially restore the bone volume.ConclusionsWe demonstrated that CPA ameliorated alcohol‐induced ONFH possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol‐induced ONFH.
Embracing fragmentation to save reindeer from disease
Authors: Mysterud Atle , Strand Olav , Rolandsen Christer M. 
Published: June 2020

AbstractSpace demanding mammalian species, such as reindeer, are in decline worldwide due to habitat loss and fragmentation. Policy to restore connectivity of reindeer habitat is now put to an abrupt halt in several areas because of an outbreak of Chronic Wasting Disease in Norway, and replaced with deliberate fragmentation of the landscape by enhancing barrier effects of linear structures.
The importance of total‐body photography and sequential digital dermatoscopy for monitoring patients at increased melanoma risk
Authors: Deinlein Teresa , Michor Carina , Hofmann‐Wellenhof Rainer , Schmid‐Zalaudek Karin , Fink‐Puches Regina 
Published: June 2020

SummaryBackground and objectivesThe incidence of melanoma is rising and prevention plays an important role. Multiple nevi as well as a medical history of melanoma are important risk factors. In affected patients, a two‐step algorithm consisting of total‐body photography (TBP) and sequential digital dermatoscopy (SDD) is a helpful diagnostic tool.Patients and methodsThis was a retrospective observational study that lasted six years in order to evaluate the significance of the two‐step algorithm. Cases were evaluated based on distinct dermoscopic patterns and statistical analyses were performed with the latest version of SPSS.Results6020 dermoscopic images of 214 patients were included. TBP was performed at a mean interval of 16.9 months (SD ± 1.43 months), while SDD was performed every 9.9 months (SD ± 1.68 months). The number needed to excise was 4.6 and the number needed to monitor was 548. Excisions were mostly performed because dynamic changes were observed. A total of eleven melanomas were detected and had a mean tumor thickness of 0.44 mm (SD ± 0.15 mm; range 0.2–0.6 mm).ConclusionsInvasive melanomas had a tumor thickness of less than 0.6 mm, thus providing evidence of an effective strategy for early melanoma detection. Excisions of benign nevi were minimized as indicated by a low number needed to excise.
Participation of young people with disabilities and/or chronic conditions in low‐ and middle‐income countries: a scoping review
Authors: Schlebusch Liezl , Huus Karina , Samuels Alecia , Granlund Mats , Dada Shakila 
Published: June 2020

AimThe purpose of this scoping review was to describe and map the literature available on the participation of young people (0–21y) with disabilities and/or chronic conditions living in low‐ and middle‐income countries (LMICs).MethodA systematic search and selection process identified 78 publications. Descriptive data were extracted using a data‐charting form, and studies were mapped using the family of participation‐related constructs framework.ResultsThe findings demonstrated that, although the published evidence is steadily increasing, the participation research on this vulnerable population is still either absent or very scarce in the majority of LMICs, and very little is known about the participation of children with chronic health conditions. Most studies included in this review focused on attendance or ‘being there’.InterpretationAlthough attendance is an important aspect, more needs to be done to understand children’s experiences or involvement while attending, thus capturing both dimensions of participation.What this paper adds

There is an increasing trend in research on participation patterns of children with disabilities in low‐ and middle‐income countries.

Most research focuses on children’s attendance, or ‘being there’.

We know very little about children’s involvement, or experience, while attending daily activities.
Clinical prevalence and outcome of cardiovascular events in the first 100 days postallogeneic hematopoietic stem cell transplant
Authors: Alblooshi Rehab , Kanfar Solaf , Lord Bridgette , Atenafu Eshetu G. , Michelis Fotios V. , Pasic Ivan , Gerbitz Armin , Al‐Shaibani Zeyad , Viswabandya Auro , Kim Dennis (Dong Hwan) , Lam Wilson , Law Arjun , Mattsson Jonas , Kumar Rajat , Lipton Jeffrey H. 
Published: June 2020

AbstractIntroductionRecent advances in allogeneic hematopoietic stem cell transplant (HSCT) have allowed us to offer HSCT to older, advanced disease patients with more co‐morbidities. Cardiovascular toxicity post‐transplant is a major concern due to the increased risk of mortality. Few studies have examined the prevalence of CV events including CAD (MI, angina, PCI, CABG, CHF, arrhythmias), HTN, stroke/TIA, and death in the first 100 days post‐transplant.PatientsWe assessed the impact of pretransplant MUGA results in predicting postallogeneic HSCT CV events and overall survival in the first 100 days, and whether or not transient anthracycline‐induced cardiomyopathy or cumulative anthracycline dose affected overall survival. This retrospective, cohort study included 665 patients with a median age of 52 years who underwent HSCT from 2009 to 2015.ResultsThe most frequent CV event in the first 100 days post‐HSCT was arrhythmia seen in 2.9% of patients followed up by CHF (12.3%), MI (9%), and angina (8%). Two patients had PCI, and both survived the first 100 days. Cardiovascular risk factors predict for a poor MUGA scan but not survival. Higher dose anthracycline pretransplant predicted for a poor outcome.ConclusionA history of CV disease, MI, or CAD was the most important predictive of CV events, P‐value = .00002. 88.6% survived the first 100 days. Patients with an EF < 50% had a significant likelihood of having a CV event compared to patients with an EF > 60% (OR = 5.3, 95% CI [1.6‐18.1], P = .0219). Cumulative anthracycline dose did not have a significant impact on overall survival.
Species loss drives ecosystem function in experiments, but in nature the importance of species loss depends on dominance
Authors: Genung Mark A. , Fox Jeremy , Winfree Rachael 
Published: June 2020

AbstractAimDecades of experimental research have conclusively shown a positive relationship between species richness and ecosystem function. However, authoritative reviews find no consensus on how species loss affects function in natural communities. We analyse experimental and observational data in an identical way and test whether they produce similar results.LocationNorth America and Europe (experimental communities); global (natural communities).Time periodExperimental communities: 1998–2013; natural communities: 1982–2018.Major taxa studiedExperimental communities: temperate grassland plants; natural communities: temperate grassland plants, tropical forest trees, kelp forest producers and native bees.MethodsWe used an approach inspired by the Price equation to analyse 129 datasets from experimental and natural communities worldwide. We tested how the effects of species loss on ecosystem function varied with dominance and the non‐randomness of species loss and, in turn, how these two factors differed between experiments and observations.ResultsStudies carried out in experimental and natural communities reached different conclusions regarding the effects of species loss. First, species loss had greater effects on ecosystem function in experiments than in nature. Second, the importance of species loss was negatively correlated with dominance in nature because as dominance increased, lost species were increasingly those contributing little to ecosystem function. Although experimental and natural communities exhibited similar levels of dominance, an analogous relationship was not possible in experiments because the order of species loss was randomized by design.Main conclusionsSpecies loss was sometimes, but not always, the major driver of loss of function in nature. Variation in the importance of species loss was not messy and context dependent; instead, it was predicted by functional dominance. Although results from experimental and natural communities were similar in several key ways, they differed in that species loss was a consistent predictor of ecosystem function in experiments and not in nature.
Identification of potential mechanosensitive ion channels involved in texture discrimination during Drosophila suzukii egg‐laying behaviour
Authors: Guo L. , Zhou Z.‐D. , Mao F. , Fan X.‐Y. , Liu G.‐Y. , Huang J. , Qiao X.‐M. 
Published: June 2020

AbstractDrosophila suzukii (spotted wing drosophila) has become a major invasive insect pest of soft fruits in the America and Europe, causing severe yield losses every year. The female D. suzukii shows the oviposition preference for ripening or ripe fruit by cutting the hard skin with its serrated ovipositor. A recent study reported that mechanosensation is involved in the texture discrimination during egg‐laying behaviour in D. suzukii. However, the underlying mechanism and molecular entity that control this behaviour are not known. The transient receptor potential (TRP) channels and degenerin/epithelial sodium channels (DEG/ENaC) are two candidate gene families of mechanically activated ion channels. Thus, we first identified TRP and DEG/ENaC genes in D. suzukii by bioinformatic analysis. Using transcriptome sequencing, we found that many TRP genes were expressed in the ovipositor in both D. suzukii and D. melanogaster, while some DEG/ENaCs showed species‐specific expression patterns. Exposure to drugs targeting TRP and DEG/ENaC channels abolished the oviposition preference for harder texture in female D. suzukii. Therefore, mechanosensitive ion channels may play significant roles in the texture assessment of egg‐laying behaviour in D. suzukii, which has promising implications to further research on the development of novel control measures.
A simple method to detect leaks after left atrial appendage occlusion with Watchman
Authors: Ayhan Hüseyin , Mohanty Sanghamitra , Gedikli Ömer , Trivedi Chintan , Canpolat Ugur , Tapia Alfredo Chauca , Chen Qiong , Della Rocca Domenico G. , Gianni Carola , Salwan Anu , Annanab Alisara , MacDonald Bryan , Mayedo Angel , Burkhardt J. David , Horton Rodney , Gallinghouse Gerald J. , Di Biase Luigi , Al‐Ahmad Amin , Natale Andrea 
Published: June 2020

AbstractBackgroundWe evaluated the efficacy of a new method in identifying peri‐device leak (PDL) using morphology of the thrombus formed inside the left atrial appendage (LAA) as seen on follow‐up transesophageal echo (TEE).MethodA total of 291 consecutive patients undergoing Watchman procedure were included in this analysis. TEE was performed at 45 days postprocedure. Based on the presence of the thrombus inside the LAA behind the device, patients were grouped as (1) white (W) group: LAA completely filled with thrombus (n = 101), 2) nonwhite (NW) group: LAA completely black or mixed (part black and part white; n = 190). Follow‐up TEE was repeated at 6 and 12 months.ResultsBaseline characteristics were comparable between groups except the device size, number of patients with chicken‐wing morphology, and prevalence of left atrial “smoke” that were significantly higher in the NW group. Detection of black appearance was comparable between the pre‐coil closure image and the NW population (26/36 [72.2%] vs 99/154 [64.3%], p = .37). After adjusting for clinically relevant covariates, NW appearance of the LAA was associated with the presence of significant leak (odds ratio: 47.96, 95% confidence interval: 2.91–790.2, p < .001). The 11 patients with mixed appearance at the 6‐month TEE remained unchanged (part black and part white) at the 12‐month TEE. LAA appearance was white in all 36 patients following coil closure.ConclusionOur findings demonstrated white and nonwhite appearance of the appendage on TEE to be reliable markers of complete closure and leak respectively, following LAA occlusion with the Watchman device.