bluuebunny/crossref_metadata_2025_split huggingface dataset:
High CD123 levels enhance proliferation in response to IL-3, but reduce chemotaxis by downregulating CXCR4 expression
Authors: Wittwer Nicole L. , Brumatti Gabriela , Marchant Ceilidh , Sandow Jarrod J. , Pudney Melanie K. , Dottore Mara , D’Andrea Richard J. , Lopez Angel F. , Ekert Paul G. , Ramshaw Hayley S. 
Published: October 2019

Key Points
High CD123 expression increases proliferation and results in enhanced survival in response to low concentration of IL-3 in vitro. High CD123-expressing LSCs downregulate chemokine receptor expression, affecting niche interactions.
Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia
Authors: Cahu Xavier , Calvo Julien , Poglio Sandrine , Prade Nais , Colsch Benoit , Arcangeli Marie-Laure , Leblanc Thierry , Petit Arnaud , Baleydier Frederic , Baruchel Andre , Landman-Parker Judith , Junot Christophe , Larghero Jerome , Ballerini Paola , Delabesse Eric , Uzan Benjamin , Pflumio Francoise 
Published: October 2019

Key Points
BM niches differentially support T-ALL. BM niches differentially protect T-ALL cells from chemotherapy.
Immune signatures associated with improved progression-free and overall survival for myeloma patients treated with AHSCT
Authors: Ho Christine M. , McCarthy Philip L. , Wallace Paul K. , Zhang Yali , Fora Ahmad , Mellors Patrick , Tario Joseph D. , McCarthy Benjamin L. S. , Chen George L. , Holstein Sarah A. , Balderman Sophia R. , Cao Xuefang , Paiva Bruno , Hahn Theresa 
Published: October 2019

Key Points
Specific immune phenotypes were predictive of long-term survival for MM patients undergoing transplantation. MRD status and use of maintenance therapy were associated with unique immune profiles predictive of outcome.
Mature lymphoid malignancies: origin, stem cells, and chronicity
Authors: Husby Simon , Grønbæk Kirsten 
Published: October 2019

Abstract
The chronic behavior of mature lymphoid malignancies, with relapses occurring years apart in many patients, has until recently been unexplained. Patterns of relapse also differ vastly between disease entities, with some being highly curable by chemotherapy whereas others are destined to reemerge after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source of mature lymphoid malignancy and discuss the perspectives.
Allogeneic bone marrow transplant in the absence of cytoreductive conditioning rescues mice with β-thalassemia major
Authors: Huo Yongliang , Lockhart Jonathan R. , Liu Shanrun , Fontenard Suean , Berlett Mike , Ryan Thomas M. 
Published: October 2019

Key PointsAfter completion of the fetal-to-adult globin gene switch, humanized β-thalassemia major mice are transfusion dependent. Perinatal humanized β-thalassemia major mice are rescued by bone marrow transplantation in the absence of cytoreductive conditioning.
Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy
Authors: Spiegel Jay Y. , McNamara Caroline , Kennedy James A. , Panzarella Tony , Arruda Andrea , Stockley Tracy , Sukhai Mahadeo , Thomas Mariam , Bartoszko Justyna , Ho Jenny , Siddiq Nancy , Maze Dawn , Schimmer Aaron , Schuh Andre , Sibai Hassan , Yee Karen , Claudio Jamie , Devlin Rebecca , Minden Mark D. , Kamel-Reid Suzanne , Gupta Vikas 
Published: October 2019

Key Points
ASXL1/EZH2, transfusion dependence, and a high prognostic risk score predict shorter TTF in MF patients on JAK1/2 inhibitors. These clinical and genetic factors were also associated with decreased overall survival.
TLR2 agonism reverses chemotherapy-induced neutropenia in Macaca fascicularis
Authors: Laping Nicholas J. , DeMartino Michael P. , Cottom Joshua E. , Axten Jeffrey M. , Emery John G. , Guss Jeffrey H. , Burman Miriam , Foley James J. , Cheung Mui , Oliff Allen , Kumar Sanjay 
Published: October 2019

Key PointsA novel TLR2 agonist was identified that stimulates the release of G-CSF, IL-6, and monocyte chemoattractant protein 1. This agonist increases neutrophil numbers in a primate model of neutropenia.
Early progression of disease as a predictor of survival in chronic lymphocytic leukemia
Authors: Ahn Inhye E. , Farber Charles M. , Davids Matthew S. , Grinblatt David L. , Kay Neil E. , Lamanna Nicole , Mato Anthony , Nabhan Chadi , Kiselev Pavel , Swern Arlene S. , Flick E. Dawn , Sullivan Kristen , Sharman Jeff P. , Flowers Christopher R. 
Published: October 2019

Key Points
Early progression of disease within 2 years of initial therapy independently predicts inferior survival in CLL. Early progression of disease is a robust clinical end point and a useful posttreatment risk stratification tool.
Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy
Authors: Gong Zimu , Medeiros L. Jeffrey , Cortes Jorge E. , Chen Zi , Zheng Lan , Li Yan , Bai Shi , Lin Pei , Miranda Roberto N. , Jorgensen Jeffrey L. , McDonnell Timothy J. , Wang Wei , Kantarjian Hagop M. , Hu Shimin 
Published: October 2019

Key Points
CML patients can be stratified into 4 subgroups with different risk of blastic transformation based on cytogenetic abnormalities. TKI therapy mitigates risk of blastic transformation associated with low-risk ACAs or no ACAs but not that associated with HR ACAs.
Maintenance of telomere length in AML
Authors: Lansdorp Peter M. 
Published: October 2019

Abstract
The importance of telomere length to human health, aging, and cancer continues to be underappreciated. This review examines some basics of telomere biology and relates how telomere function, telomerase activity, and mutations in TERC or TERT are involved in bone marrow failure, leukemias, and other cancers. Given the challenge to obtain accurate data on telomerase activity and telomere length in specific cell types, the situation in acute myeloid leukemia (AML) remains puzzling. In most cancers, telomerase levels are increased after cells have encountered a “telomere crisis,” which is typically associated with poor prognosis. Cells emerging from “telomere crisis” have defective DNA damage responses, resulting, for example, from loss of p53. Such cells often express elevated telomerase levels as a result of point mutations in the TERT promoter or amplification of the TERT gene. While telomeres in AML blasts are typically shorter than expected for normal leukocytes, most AML cells do not show evidence of having gone through a “telomere crisis.” In chronic myeloid leukemia (CML), the difference between the telomere length in nonmalignant T cells and malignant blasts from the same patient was found to correlate with the remaining duration of the chronic phase. This observation supports that a mitotic clock is ticking in CML stem cells and that disease progression in CML heralds the onset of a “telomere crisis.” The presence of very short telomeres in tumor cells was found to predict disease progression in chronic lymphocytic leukemia, myeloma, and various solid tumors. In view of these findings longitudinal studies of telomere length in AML appear worthwhile.
A B-cell–associated gene signature classification of diffuse large B-cell lymphoma by NanoString technology
Authors: Michaelsen Thomas Yssing , Richter Julia , Brøndum Rasmus Froberg , Klapper Wolfram , Johnsen Hans Erik , Albertsen Mads , Dybkær Karen , Bøgsted Martin 
Published: October 2019

Key PointsA gene expression assay that accurately assigns B-cell–associated gene signatures to DLBCL with prognostic impact. Robust performance irrespective of sample preparation method and GEP platform.
Prevalence and associated factors for needlestick and sharp injuries (NSIs) among dental assistants in Jeddah, Saudi Arabia
Authors: AlDakhil Lama , Yenugadhati Nagarajkumar , Al-Seraihi Ohoud , Al-Zoughool Mustafa 
Published: October 2019

Abstract

Background
Dental personnel are subject to exposure to a number of occupational factors including needlestick and sharp injuries (NSIs). Our study aims to address knowledge gaps on prevalence and associated factors for needlestick and sharp injuries (NSIs) for the first time in Saudi Arabia.

Methods
This cross-sectional study was conducted on a sample of 450 dental assistants recruited from 40 randomly selected private clinics in Jeddah, Saudi Arabia. Data on demographic characteristics, history of NSIs, nature of work, compliance with infection control protocols, and knowledge of infection control procedures and disease transmission were collected using a self-administered questionnaire. Logistic regression analysis was used to assess factors associated with NSIs; unadjusted and adjusted odds ratios (aORs) and their respective 95% confidence intervals (CIs) were computed.

Results
About three in ten dental assistants experienced at least one NSI (29.8%, 95% CI 25.6–34.2%) in private dental clinics. Lack of adequate knowledge of infection control procedures and disease transmission, non-compliance with infection control protocol of vaccination against hepatitis B virus, and attending 12 or less number of patients daily were significantly associated with increased risk of NSIs (p ≤ 0.05); adjusted odds ratios (95% CI) were 1.87 (1.18–2.97), 1.89 (1.05–3.41), and 1.63 (1.03–2.56), respectively. In addition, dental assistants working in 45.8% of dental clinics that had no infection control unit were positively associated with higher NSI risk (aOR = 2.28, 95% CI 1.45–3.57).

Conclusion
Our study reported the prevalent nature of NSIs among dental assistants in Saudi Arabia and identified key factors that could be targeted to mitigate this preventable condition. Dental assistants would benefit from proper training on infection control protocols and procedures.
Moss species-specific accumulation of atmospheric deposition?
Authors: Schröder Winfried , Nickel Stefan 
Published: October 2019

Abstract

Background
This article presents statistical analyses of elements concentrations in mosses collected in two monitoring programmes: 1. The German moss monitoring as part of the European Moss Survey conducted in 1990, 1995, 2000, 2005 and 2015 at 592, 1026, 1028, 726 and 400 sites across Germany, respectively, and chemically analysed according to harmonised methods throughout Europe; and 2. The moss surveys additionally performed throughout Bavaria, federal state of Germany. The evaluations of the present study are intended to examine indications whether the element accumulations are specific to moss species and whether, therefore, conversion factors should be used. Such observations and recommendations have so far been limited to spatially confined areas and relatively few moss samples and were derived from different studies without a common methodology. Therefore, the objective of this investigation was to analyse large and long-term datasets from moss surveys for differences in element concentrations in different moss species. This analysis was based on data derived from several moss species collected across Germany and specimens of only one moss species collected in the monitoring programme performed by the environmental authority of Bavaria. So far, the presented investigation is the most comprehensive one in terms of running time, spatial density of the measurement network and method harmonisation.

Results
The present study does neither verify nor falsify the hypothesis of moss species-specific element accumulations in mosses. This, like the other studies, is not possible because of its empirical design, since that would require strictly controlled laboratory experiments. However, this investigation yielded hints, that the differences in element accumulation in several moss species across German surveys between 1990 and 2015 are in the range of the intra- and inter-specific variance reported.

Conclusion
It is, therefore, advisable to continue dispensing with conversion factors so far.
Benchmark datasets of immune receptor-epitope structural complexes
Authors: Mahajan Swapnil , Yan Zhen , Jespersen Martin Closter , Jensen Kamilla Kjærgaard , Marcatili Paolo , Nielsen Morten , Sette Alessandro , Peters Bjoern 
Published: October 2019

AbstractBackgroundThe development of accurate epitope prediction tools is important in facilitating disease diagnostics, treatment and vaccine development. The advent of new approaches making use of antibody and TCR sequence information to predict receptor-specific epitopes have the potential to transform the epitope prediction field. Development and validation of these new generation of epitope prediction methods would benefit from regularly updated high-quality receptor-antigen complex datasets.ResultsTo address the need for high-quality datasets to benchmark performance of these new generation of receptor-specific epitope prediction tools, a webserver called SCEptRe (Structural Complexes of Epitope-Receptor) was created. SCEptRe extracts weekly updated 3D complexes of antibody-antigen, TCR-pMHC and MHC-ligand from the Immune Epitope Database and clusters them based on antigen, receptor and epitope features to generate benchmark datasets. SCEptRe also provides annotated information such as CDR sequences and VDJ genes on the receptors. Users can generate custom datasets based by selecting thresholds for structural quality and clustering parameters (e.g. resolution, R-free factor, antigen or epitope sequence identity) based on their need.ConclusionsSCEptRe provides weekly updated, user-customized comprehensive benchmark datasets of immune receptor-epitope structural complexes. These datasets can be used to develop and benchmark performance of receptor-specific epitope prediction tools in the future. SCEptRe is freely accessible athttp://tools.iedb.org/sceptre.
Interleukin-6 mediates resistance to PI3K-pathway–targeted therapy in lymphoma
Authors: Kim Joo Hyun , Kim Won Seog , Park Chaehwa 
Published: October 2019

Abstract

Background
The phosphoinositol 3-kinase (PI3K) pathway is associated with poor prognosis of hematologic malignancies, providing a strong rationale for the use of PI3K inhibitors in the treatment of malignant lymphoma. However, development of resistance limits the use of PI3K inhibitors in lymphoma patients.

Methods
We established copanlisib (pan-PI3K inhibitor)-resistant B-cell lymphoma and duvelisib (PI3Kδ and -γ inhibitor)-resistant T-cell lymphoma cell lines. The cytokine array and the phospho-kinase array were used to identify up-regulated proteins in the resistant cells. Cytokine expression and phospho-kinase levels were examined by ELISA and Western blot analysis, respectively. Cell proliferation capabilities were measured by using CCK-8 kit and colony formation assay. The effects of inhibitors on apoptosis were detected using an Annexin V-FITC Apoptosis Detection Kit and a flow cytometry system. The underlying mechanisms were studied by transfecting recombinant plasmids or siRNA into lymphoma cell lines. Cells were transiently transfected using the Amaxa electroporation system. We evaluated the effects of PI3K inhibitor alone and in combination with JAK inhibitor (BSK805) on lymphoma proliferation and signaling pathway activation.

Results
Cytokine arrays revealed upregulation of interleukin (IL)-6 in both copanlisib- and duvelisib-resistant cell lines. Phosphorylated STAT5, AKT, p70S6K and MAPK were increased in copanlisib-resistant B-cell lymphoma cells, whereas phosphorylated STAT3 and NF-κB were increased in duvelisib-resistant T cell lymphoma cells. Conversely, depletion of IL-6 sensitized both resistant cell lines, and led to downregulation of phosphorylated STAT3 and STAT5 in copanlisib- and duvelisib-resistant cells, respectively. Moreover, combined treatment with a JAK inhibitor (BSK805) and a PI3K inhibitor circumvented the acquired resistance to PI3K inhibitors in lymphoma, and concurrent inhibition of the activated pathways produced combined effects.

Conclusions
IL-6–induced STAT3 or STAT5 activation is a critical mechanism underlying PI3K inhibitor resistance in lymphoma, supporting the utility of IL-6 as an effective biomarker to predict therapeutic response to PI3K inhibitors.
Maternal cardiometabolic markers are associated with fetal growth: a secondary exploratory analysis of the LIMIT randomised trial
Authors: O’Brien Cecelia M. , Louise Jennie , Deussen Andrea , Dodd Jodie M. 
Published: October 2019

Abstract

Background
To determine the association between maternal cardiometabolic and inflammatory markers with measures of fetal biometry and adiposity.

Methods
Women included in this exploratory analysis were randomised to the ‘Standard Care’ group (N = 911) from the LIMIT randomised trial involving a total of 2212 pregnant women who were overweight or obese (ACTRN12607000161426, Date of registration 9/03/2007, prospectively registered). Fetal biometry including abdominal circumference (AC), estimated fetal weight (EFW), and adiposity measurements (mid-thigh fat mass, subscapular fat mass, abdominal fat mass) were obtained from ultrasound assessments at 28 and 36 weeks’ gestation. Maternal markers included C reactive protein (CRP), leptin and adiponectin concentrations, measured at 28 and 36 weeks’ gestation and fasting triglycerides and glucose concentrations measured at 28 weeks’ gestation.

Results
There were negative associations identified between maternal serum adiponectin and fetal ultrasound markers of biometry and adiposity. After adjusting for confounders, a 1-unit increase in log Adiponectin was associated with a reduction in the mean AC z score [− 0.21 (− 0.35, − 0.07), P = 0.004] and EFW [− 0.23 (− 0.37, − 0.10), P < 0.001] at 28 weeks gestation. Similarly, a 1-unit increase in log Adiponectin was association with a reduction in the mean AC z score [− 0.30 (− 0.46, − 0.13), P < 0.001] and EFW [− 0.24 (− 0.38, − 0.10), P < 0.001] at 36 weeks gestation. There were no consistent associations between maternal cardiometabolic and inflammatory markers with measurements of fetal adiposity.

Conclusion
Adiponectin concentrations are associated with measures of fetal growth. Our findings contribute to further understanding of fetal growth in the setting of women who are overweight or obesity.
EQUIP Emergency: study protocol for an organizational intervention to promote equity in health care
Authors: Varcoe Colleen , Bungay Vicky , Browne Annette J. , Wilson Erin , Wathen C. Nadine , Kolar Kat , Perrin Nancy , Comber Scott , Blanchet Garneau Amélie , Byres David , Black Agnes , Price Elder Roberta 
Published: October 2019

Abstract

Background
Social inequities are widening globally, contributing to growing health and health care inequities. Health inequities are unjust differences in health and well-being between and within groups of people caused by socially structured, and thus avoidable, marginalizing conditions such as poverty and systemic racism. In Canada, such conditions disproportionately affect Indigenous persons, racialized newcomers, those with mental health and substance use issues, and those experiencing interpersonal violence. Despite calls to enhance equity in health care to contribute to improving population health, few studies examine how to achieve equity at the point of care, and the impacts of doing so. Many people facing marginalizing conditions experience inadequate and inequitable treatment in emergency departments (EDs), which makes people less likely to access care, paradoxically resulting in reliance on EDs through delays to care and repeat visits, interfering with effective care delivery and increasing human and financial costs. EDs are key settings with potential for mitigating the impacts of structural conditions and barriers to care linked to health inequities.

Methods
EQUIP is an organizational intervention to promote equity. Building on promising research in primary health care, we are adapting EQUIP to emergency departments, and testing its impact at three geographically and demographically diverse EDs in one Canadian province. A mixed methods multisite design will examine changes in key outcomes including: a) a longitudinal analysis of change over time based on structured assessments of patients and staff, b) an interrupted time series design of administrative data (i.e., staff sick leave, patients who leave without care being completed), c) a process evaluation to assess how the intervention was implemented and the contextual features of the environment and process that are influential for successful implementation, and d) a cost-benefit analysis.

Discussion
This project will generate both process- and outcome-based evidence to improve the provision of equity-oriented health care in emergency departments, particularly targeting groups known to be at greatest risk for experiencing the negative impacts of health and health care inequities. The main deliverable is a health equity-enhancing framework, including implementable, measurable interventions, tested, refined and relevant to diverse EDs.

Trial registration
Clinical Trials.gov #NCT03369678 (registration date November 18, 2017).
Transcriptomic and functional analysis of the oosome, a unique form of germ plasm in the wasp Nasonia vitripennis
Authors: Quan Honghu , Arsala Deanna , Lynch Jeremy A. 
Published: October 2019

AbstractBackgroundThe oosome is the germline determinant in the waspNasonia vitripennisand is homologous to the polar granules ofDrosophila. Despite a common evolutionary origin and developmental role, the oosome is morphologically quite distinct from polar granules. It is a solid sphere that migrates within the cytoplasm before budding out and forming pole cells.ResultsTo gain an understanding of both the molecular basis of oosome development and the conserved essential features of germ plasm, we quantified and compared transcript levels between embryo fragments that contained the oosome and those that did not. The identity of the differentially localized transcripts indicated thatNasoniauses a distinct set of molecules to carry out conserved germ plasm functions. In addition, functional testing of a sample of localized transcripts revealed potentially novel mechanisms of ribonucleoprotein assembly and pole cell cellularization in the wasp.ConclusionsOur results demonstrate that the composition of germ plasm varies significantly within Holometabola, as very few mRNAs share localization to the oosome and polar granules. Some of this variability appears to be related to the unique properties of the oosome relative to the polar granules inDrosophila, and some may be related to differences in pole formation between species. This work will serve as the basis for further investigation into the patterns of germline determinant evolution among insects, the molecular basis of the unique properties of the oosome, and the incorporation of novel components into developmental networks.