bluuebunny/crossref_metadata_2025_split huggingface dataset:
External validation of models for KIR2DS1/KIR3DL1-informed selection of hematopoietic cell donors fails
Authors: Schetelig Johannes , Baldauf Henning , Heidenreich Falk , Massalski Carolin , Frank Sandra , Sauter Jürgen , Stelljes Matthias , Ayuk Francis Ayuketang , Bethge Wolfgang A. , Bug Gesine , Klein Stefan , Wendler Sarah , Lange Vinzenz , de Wreede Liesbeth C. , Fürst Daniel , Kobbe Guido , Ottinger Hellmut D. , Beelen Dietrich W. , Mytilineos Joannis , Fleischhauer Katharina , Schmidt Alexander H. , Bornhäuser Martin 
Published: January 2020

Abstract
Several studies suggest that harnessing natural killer (NK) cell reactivity mediated through killer cell immunoglobulin-like receptors (KIRs) could reduce the risk of relapse after allogeneic hematopoietic cell transplantation. Based on one promising model, information on KIR2DS1 and KIR3DL1 and their cognate ligands can be used to classify donors as KIR-advantageous or KIR-disadvantageous. This study was aimed at externally validating this model in unrelated donor hematopoietic cell transplantation. The impact of the predictor on overall survival (OS) and relapse incidence was tested in a Cox regression model adjusted for patient age, a modified disease risk index, Karnofsky performance status, donor age, HLA match, sex match, cytomegalovirus match, conditioning intensity, type of T-cell depletion, and graft type. Data from 2222 patients with acute myeloid leukemia or myelodysplastic syndrome were analyzed. KIR genes were typed by using high-resolution amplicon-based next-generation sequencing. In univariable analyses and subgroup analyses, OS and the cumulative incidence of relapse of patients with a KIR-advantageous donor were comparable to patients with a KIR-disadvantageous donor. The adjusted hazard ratio from the multivariable Cox regression model was 0.99 (Wald test, P = .93) for OS and 1.04 (Wald test, P = .78) for relapse incidence. We also tested the impact of activating donor KIR2DS1 and inhibition by KIR3DL1 separately but found no significant impact on OS and the risk of relapse. Thus, our study shows that the proposed model does not universally predict NK-mediated disease control. Deeper knowledge of NK-mediated alloreactivity is necessary to predict its contribution to graft-versus-leukemia reactions and to eventually use KIR genotype information for donor selection.
Clinical diagnostics and treatment strategies for Philadelphia chromosome–like acute lymphoblastic leukemia
Authors: Harvey Richard C. , Tasian Sarah K. 
Published: January 2020

Abstract
Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) accounts for 15% to 30% of B-cell acute lymphoblastic leukemia in older children, adolescents, and adults and is associated with high rates of conventional treatment failure and relapse. Current clinical trials are assessing the efficacy of the addition of tyrosine kinase inhibitors (TKIs) to chemotherapy for children and adults with Ph-like ALL harboring ABL class translocations or CRLF2 rearrangements and other JAK pathway alterations. However, real-time diagnosis of patients can be quite challenging given the genetic heterogeneity of this disease and the often cytogenetically cryptic nature of Ph-like ALL-associated alterations. In this review, we discuss the complex biologic and clinical features of Ph-like ALL across the age spectrum, available diagnostic testing modalities, and current clinical treatment strategies for these high-risk patients. We further propose a practical and step-wise approach to Ph-like ALL genetic testing to facilitate the identification and allocation of patients to appropriate clinical trials of TKI-based therapies or commercially available drugs. Although the majority of patients with Ph-like ALL can be successfully identified via current clinical assays by the end of induction chemotherapy, increasing diagnostic efficiency and sensitivity and decreasing time to test resulting will facilitate earlier therapeutic intervention and may improve clinical outcomes for these high-risk patients.
A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry
Authors: Du Zhaohui , Weinhold Niels , Song Gregory Chi , Rand Kristin A. , Van Den Berg David J. , Hwang Amie E. , Sheng Xin , Hom Victor , Ailawadhi Sikander , Nooka Ajay K. , Singhal Seema , Pawlish Karen , Peters Edward S. , Bock Cathryn , Mohrbacher Ann , Stram Alexander , Berndt Sonja I. , Blot William J. , Casey Graham , Stevens Victoria L. , Kittles Rick , Goodman Phyllis J. , Diver W. Ryan , Hennis Anselm , Nemesure Barbara , Klein Eric A. , Rybicki Benjamin A. , Stanford Janet L. , Witte John S. , Signorello Lisa , John Esther M. , Bernstein Leslie , Stroup Antoinette M. , Stephens Owen W. , Zangari Maurizio , Van Rhee Frits , Olshan Andrew , Zheng Wei , Hu Jennifer J. , Ziegler Regina , Nyante Sarah J. , Ingles Sue Ann , Press Michael F. , Carpten John David , Chanock Stephen J. , Mehta Jayesh , Colditz Graham A. , Wolf Jeffrey , Martin Thomas G. , Tomasson Michael , Fiala Mark A. , Terebelo Howard , Janakiraman Nalini , Kolonel Laurence , Anderson Kenneth C. , Le Marchand Loic , Auclair Daniel , Chiu Brian C.-H. , Ziv Elad , Stram Daniel , Vij Ravi , Bernal-Mizrachi Leon , Morgan Gareth J. , Zonder Jeffrey A. , Huff Carol Ann , Lonial Sagar , Orlowski Robert Z. , Conti David V. , Haiman Christopher A. , Cozen Wendy 
Published: January 2020

Abstract
Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P &lt; 1 × 10−6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P &lt; .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10−12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.
Expression of the prosurvival kinase HCK requires PAX5 and mutated MYD88 signaling in MYD88-driven B-cell lymphomas
Authors: Liu Xia , Chen Jiaji G. , Munshi Manit , Hunter Zachary R. , Xu Lian , Kofides Amanda , Tsakmaklis Nickolas , Demos Maria G. , Guerrera Maria Luisa , Chan Gloria G. , Jimenez Cristina , Patterson Christopher J. , Meid Kirsten , Keezer Andrew , Castillo Jorge J. , Treon Steven P. , Yang Guang 
Published: January 2020

Abstract
Hematopoietic cell kinase (HCK) is an SRC family member that is aberrantly upregulated in B-cell neoplasms dependent on MYD88-activating mutations and supports their growth and survival. We showed herein that activation of Toll-like receptor (TLR) signaling in MYD88 wild-type B cells also triggered HCK expression, denoting on path regulatory function for HCK by MYD88. To clarify the signaling cascades responsible for aberrant HCK expression in MYD88-mutated B-cell lymphomas, we performed promoter-binding transcription factor (TF) profiling, PROMO weighted TF consensus binding motif analysis, and chromatin immunoprecipitation studies. We identified PAX5, and the mutated MYD88 downstream signaling mediators STAT3, NF-κB, and AP-1, as important drivers of HCK transcription. Knockdown of PAX5, a crucial regulatory factor required for B-cell commitment and identity, abrogated HCK transcription in MYD88-mutated lymphoma cells. Among AP-1 complex components, JunB showed greatest relevance to TLR/MYD88 signaling and HCK transcription regulation. In MYD88-mutated Waldenström macroglobulinemia and activated B-cell-diffuse large B-cell lymphoma cells, knockdown of MYD88 reduced phosphorylation of JunB but not c-Jun, and knockdown of JunB reduced HCK protein levels. Deletion of STAT3, NF-κB, and AP-1 binding sites reduced corresponding TFs binding and HCK promoter activity. Moreover, inhibitors to STAT3, NF-κB, and AP-1 reduced HCK promoter activity and messenger RNA levels, particularly in combination, in MYD88-mutated lymphoma cells. The findings provide new insights into the transcriptional regulation of HCK prosurvival signaling by mutated MYD88, and the importance of JunB as a downstream mediator of the MYD88-directed signaling apparatus.
Five-year results of the BEGEV salvage regimen in relapsed/refractory classical Hodgkin lymphoma
Authors: Santoro Armando , Mazza Rita , Pulsoni Alessandro , Re Alessandro , Bonfichi Maurizio , Zilioli Vittorio Ruggero , Zanni Manuela , Merli Francesco , Anastasia Antonella , Luminari Stefano , Annechini Giorgia , Gotti Manuel , Peli Annalisa , Liberati Anna Marina , Di Renzo Nicola , Castagna Luca , Giordano Laura , Ricci Francesca , Carlo-Stella Carmelo 
Published: January 2020

Abstract
The complete remission (CR) rate achieved with induction chemotherapy prior to autologous stem cell transplantation (ASCT) represents the strongest prognostic factor in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). By inducing a CR rate of 75%, the bendamustine, gemcitabine, vinorelbine (BEGEV) regimen represents an optimal chemotherapy regimen prior to ASCT. Presented here are the 5-year results of BEGEV followed by ASCT in R/R cHL. With a median follow-up of 5 years, progression-free survival (PFS) and overall survival (OS) for the whole series (n = 59) were 59% and 78%, respectively. ASCT was performed in 43 of 49 responding patients (73% by intention to treat [ITT]; 88% by response to BEGEV) and resulted in 33 with continuous CR (56% by ITT; 77% of transplanted patients), 7 with disease relapse, and 3 with nonrelapse mortality. For patients who received transplants, the 5-year PFS and OS were 77% and 91%, respectively, with no significant difference between relapsed and refractory patients. No patient experienced secondary leukemia or myelodysplasia. In summary, the long-term efficacy data, the benefits for both relapsed and refractory patients, and the excellent safety profile provide a strong rationale for further development of the BEGEV regimen. This trial was registered at EudraCT as #2010-022169-91 and at www.clinicaltrials.gov as #NCT01884441.
Maximum tumor diameter is associated with event-free survival in PET-negative patients with stage I/IIA Hodgkin lymphoma
Authors: Illidge Tim M. , Phillips Elizabeth H. , Counsell Nicholas , Pettengell Ruth , Johnson Peter W. M. , Culligan Dominic J. , Popova Bilyana , Clifton-Hadley Laura , McMillan Andrew , Hoskin Peter , Barrington Sally F. , Radford John 
Published: January 2020

Key Points
Baseline maximum tumor diameter is an important predictor of relapse for patients with ES-HL achieving complete metabolic remission. Patients with baseline tumor size ≥5 cm have worse outcomes with ABVD alone and are likely to benefit from consolidation radiotherapy.
Enhanced genome assembly and a new official gene set for Tribolium castaneum
Authors: Herndon Nicolae , Shelton Jennifer , Gerischer Lizzy , Ioannidis Panos , Ninova Maria , Dönitz Jürgen , Waterhouse Robert M. , Liang Chun , Damm Carsten , Siemanowski Janna , Kitzmann Peter , Ulrich Julia , Dippel Stefan , Oberhofer Georg , Hu Yonggang , Schwirz Jonas , Schacht Magdalena , Lehmann Sabrina , Montino Alice , Posnien Nico , Gurska Daniela , Horn Thorsten , Seibert Jan , Vargas Jentzsch Iris M. , Panfilio Kristen A. , Li Jianwei , Wimmer Ernst A. , Stappert Dominik , Roth Siegfried , Schröder Reinhard , Park Yoonseong , Schoppmeier Michael , Chung Ho-Ryun , Klingler Martin , Kittelmann Sebastian , Friedrich Markus , Chen Rui , Altincicek Boran , Vilcinskas Andreas , Zdobnov Evgeny , Griffiths-Jones Sam , Ronshaugen Matthew , Stanke Mario , Brown Sue J. , Bucher Gregor 
Published: January 2020

AbstractBackgroundThe red flour beetleTribolium castaneumhas emerged as an important model organism for the study of gene function in development and physiology, for ecological and evolutionary genomics, for pest control and a plethora of other topics. RNA interference (RNAi), transgenesis and genome editing are well established and the resources for genome-wide RNAi screening have become available in this model. All these techniques depend on a high quality genome assembly and precise gene models. However, the first version of the genome assembly was generated by Sanger sequencing, and with a small set of RNA sequence data limiting annotation quality.ResultsHere, we present an improved genome assembly (Tcas5.2) and an enhanced genome annotation resulting in a new official gene set (OGS3) forTribolium castaneum, which significantly increase the quality of the genomic resources. By adding large-distance jumping library DNA sequencing to join scaffolds and fill small gaps, the gaps in the genome assembly were reduced and the N50 increased to 4753kbp. The precision of the gene models was enhanced by the use of a large body of RNA-Seq reads of different life history stages and tissue types, leading to the discovery of 1452 novel gene sequences. We also added new features such as alternative splicing, well defined UTRs and microRNA target predictions. For quality control, 399 gene models were evaluated by manual inspection. The current gene set was submitted to Genbank and accepted as a RefSeq genome by NCBI.ConclusionsThe new genome assembly (Tcas5.2) and the official gene set (OGS3) provide enhanced genomic resources for genetic work inTribolium castaneum. The much improved information on transcription start sites supports transgenic and gene editing approaches. Further, novel types of information such as splice variants and microRNA target genes open additional possibilities for analysis.
Proportion of NAFLD patients with normal ALT value in overall NAFLD patients: a systematic review and meta-analysis
Authors: Ma Xuefeng , Liu Shousheng , Zhang Jie , Dong Mengzhen , Wang Yifen , Wang Mengke , Xin Yongning 
Published: January 2020

Abstract
Background
ALT value is often used to reflect the hepatic inflammation and injury in NAFLD patients, but many studies proved that ALT values were normal in many NAFLD patients. The aim of this study was to identify the summarized proportion of NAFLD patients with normal ALT value in the overall NAFLD patients.

Methods
Electronic databases PubMed, EMBASE, Ovid, and the Cochrane Library were searched for potential studies published from January 1, 2000 to September 30, 2019. Studies that have reported the number of NAFLD or NASH patients with normal and abnormal ALT value were included and analyzed. Abstracts, reviews, case reports, and letters were excluded.

Results
A total of 11 studies with 4084 patients were included for assessing the summarized proportion of NAFLD patients with normal ALT in overall NAFLD patients. As the results shown, the summarized proportion of NAFLD patients with normal ALT value in overall NAFLD patients was 25% (95%CI: 20–31%) which was calculated by the random-effects model. The summarized proportion of NASH patients with normal ALT value in overall NASH patients was 19% (95%CI: 13–27%). Subgroup analysis includes region, study type, diagnostic method, and group size were conducted to investigate the resource of heterogeneity in the summarized proportion of NAFLD and NASH patients with normal ALT value.

Conclusions
25% NAFLD patients and 19% NASH patients possess the normal ALT value in the clinical manifestation. The value of ALT in the clinical diagnosis of NAFLD and NASH remains need be further testified.
Associations between disease activity, social support and health-related quality of life in patients with inflammatory bowel diseases: the mediating role of psychological symptoms
Authors: Fu Hanlin , Kaminga Atipatsa Chiwanda , Peng Yan , Feng Tiejian , Wang Tingting , Wu Xiaobing , Yang Tubao 
Published: January 2020

Abstract
Background
Previous studies have indicated that disease activity, psychological symptoms and social support were associated with health-related quality of life (HRQoL) in patients with inflammatory bowel diseases(IBD). However, it is unclear how disease activity, psychological symptoms and social support interact to affect HRQoL. The main purpose of this study was to examine the mediation effect of psychological symptoms in the relationship between disease activity, social support and HRQoL.

Methods
This was a cross-sectional study, which collected data using convenience sampling, between December 2016 and March 2018, from the Third XiangyaHospital of Central South University in Changsha, China. An online self-administered questionnaire (including demographic and clinical information), Inflammatory Bowel Disease Questionnaire, Disease Activity Indices scale, Hospital Anxiety and Depression Scale and Social Support Rating Scale, were administered to each participant. Descriptive statistics and Pearson’s correlations were used to summarize data, whereas PROCESS analysis was performed to examine the pre-specified mediation effect.

Results
A total of 199 patients with IBD were included. Disease activity indices (DAI) and hospital anxiety and depression (HAD) were negatively correlated with HRQoL (β = − 3.37, − 2.54 respectively, P < 0.001), while social support was positively correlated with HRQoL (β = 1.38, P < 0.01). HAD partially mediated the negative relationship between DAI and HRQoL (β = − 0.83, P < 0.001) with the mediation effect ratio of 24.6%, and completely mediated the positive relationship between social support and HRQoL (β = 1.20, P < 0.001).

Conclusions
Psychological symptoms acted as a mediator in the relationship between disease activity, social support and HRQoL. Interventions to improve HRQoL in patients with IBD should take into account the mediation effect of psychological symptoms.
Pain and recurrent falls in the older and oldest-old non-institutionalized population
Authors: Gálvez-Barrón César , Formiga Francesc , Miñarro Antonio , Macho Oscar , Narvaiza Leire , Dapena María Dolores , Pujol Ramon , Rodríguez-Molinero Alejandro 
Published: January 2020

AbstractBackgroundRecurrent falls represent a priority in geriatric research. In this study we evaluated the influence of pain as a risk factor for recurrent falls (two or more in 1 year) in the older (65–79 years) and oldest-old (80 or more years) non-institutionalized population.MethodsProspective cohort study. 772 non-institutionalized individuals with ages of 65 years or older (with overrepresentation of people aged 80 years or older [n = 550]) were included through randomized and multistage sampling, stratified according to gender, geographic area and habitat size. Basal evaluation at participant’s home including pain evaluation by Face Pain Scale (FPS, range 0–6) and then telephonic contact every 3 months were performed until complete 12 months. Multivariate analysis by logistic regression (recurrent falls as outcome variable) for each age group (older and oldest-old group) were developed considering pain as a quantitative variable (according to FPS score). Models were adjusted for age, gender, balance, muscle strength, depressive symptoms, cognitive decline, number of drugs and number of drugs with risk of falls.Results114 (51.35%) and 286 (52%) participants of older and oldest-old group, respectively, reported pain; and recurrent falls occurred in 6.93% (n = 12) of the older group and 12.06% (n = 51) of the oldest-old group. In the older group, pain was associated with recurrent falls, with an associated odds ratio (OR) of 1.47 (95% CI 1.08–2.00; beta 0.3864) for each unit increase in pain intensity (thus, participants with the most severe pain [FPS 6] had OR of 10.16 regarding to participants without pain [FPS 0]). In the oldest-old group, pain was not associated with recurrent falls.ConclusionsPain, a potentially modifiable and highly prevalent symptom, is a risk factor for recurrent falls in the older people (65–79 years). However, we have not been able to demonstrate that this relationship is maintained in the oldest-old population (80 or more years).
Hemodynamic response to non-pneumatic anti-shock compression garments in patients with renal dysfunction
Authors: Marinovich R. , Li Z. , Tamasi T. , Quinn K. , Wong S. , McIntyre C. W. 
Published: January 2020

Abstract
Background
Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. Chronic exposure to intermittent hemodialysis may be a source of added stress to the cardiovascular system; intradialytic hypotension is a common complication of hemodialysis, and repeated events may lead to hemodynamic stress and ischemic injuries. Administration of non-pneumatic compression stockings to the lower limbs has demonstrated hemodynamic stabilizing effects in other settings and may provide similar benefits in the kidney disease population. Therefore, we conducted this pilot study assessing the feasibility and tolerability of the application of non-pneumatic compression stockings to patients with kidney disease. We also assessed the changes in hemodynamic measurements following the application of the compression stockings to explore the biological feasibility of this being an effective intervention for intradialytic hypotension.

Methods
Fifteen individuals were enrolled in the study (5 healthy, 5 chronic kidney disease patients, and 5 dialysis patients). Outcomes including hemodynamic parameters such as cardiac output, peripheral vascular resistance, and blood pressure were measured using continuous pulse wave analysis. Changes in global longitudinal strain were measured via echocardiography. These outcome measurements were made before and after the application of compression stockings.

Results
All study participants tolerated the compression garments well and without complication. Hemodynamic response to lower body compression caused varying effects on cardiac output, mean arterial pressure and global longitudinal strain. Some individuals saw large improvements in hemodynamic parameters while in others the opposite effect was observed. No consistent response was elicited.

Conclusions
Application of compression stockings to patients with renal dysfunction is well-tolerated. However, significant variations in hemodynamic outcomes exist, and may be a barrier for larger scale trials without prior identification of specific patient characteristics indicating likely benefit from the application of external compression.

Trial registration
ClinicalTrials.gov, Identifier: NCT02915627, Registration Date: Sept 27, 2016.