bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population-based cohort of 500 patients with Gaucher disease in Israel
Authors: Jaffe Dena H , Flaks-Manov Natalie , Benis Arriel , Gabay Hagit , DiBonaventura Marco , Rosenbaum Hanna , Joseph Alain , Bachrach Asaf , Leventer-Roberts Maya 
Published: January 2019

ObjectiveTo characterise a population-based cohort of patients with Gaucher disease (GD) in Israel relative to the general population and describe sociodemographic and clinical differences by disease severity (ie, enzyme replacement therapy [ERT] use).DesignA cross-sectional study was conducted.SettingData from the Clalit Health Services electronic health record (EHR) database were used.ParticipantsThe study population included all patients in the Clalit EHR database identified as having GD as of 30 June 2014.ResultsA total of 500 patients with GD were identified and assessed. The majority were ≥18 years of age (90.6%), female (54.0%), Jewish (93.6%) and 34.8% had high socioeconomic status, compared with 19.0% in the general Clalit population. Over half of patients with GD with available data (51.0%) were overweight/obese and 63.5% had a Charlson Comorbidity Index ≥1, compared with 46.6% and 30.4%, respectively, in the general Clalit population. The majority of patients with GD had a history of anaemia (69.6%) or thrombocytopaenia (62.0%), 40.4% had a history of bone events and 22.2% had a history of cancer. Overall, 41.2% had received ERT.ConclusionsEstablishing a population-based cohort of patients with GD is essential to understanding disease progression and management. In this study, we highlight the need for physicians to monitor patients with GD regardless of their ERT status.
Cross-sectional research conducted in the Netherlands to identify relationships among the actual level of patient-centred care, the care gap (ideal vs actual care delivery) and satisfaction with care
Authors: Mirzad Ferogh , Cramm Jane Murray , Nieboer Anna Petra 
Published: January 2019

ObjectiveThis study aimed to identify relationships among the actual level of patient-centred care (PCC), the care gap (ideal level of PCC vs actual care delivery) and satisfaction with care.DesignThis study was a cross-sectional survey.SettingThis study was conducted at two locations of a Dutch hospital (Nieuwegein and Leidsche Rijn Utrecht).ParticipantsPatients visiting the outpatient clinics for heart failure, chronic obstructive pulmonary disease (COPD) and cancer in March–May 2017 were asked to fill in a questionnaire. Inclusion criteria were diagnosis with COPD, heart failure or cancer and clinic visitation for a regular appointment. A total of 186 patients filled in the questionnaire.Primary and secondary outcome measuresOutcomes evaluated were the actual level of PCC, the care gap and satisfaction with care.ResultsAbout half (45%) of the respondents were female, 38% had low educational levels and 31% were single. Respondents’ mean age was 67.83 ± 10.02 (range, 16–94) years. Patients’ experiences with actual care delivery and their conceptualisation of the ideal type of care differed significantly, representing care gaps, in all PCC dimensions. After controlling for background characteristics, patients’ experiences with actual delivery and the care gap were related significantly to patients’ satisfaction with care (β = 0.17 and β = – 0.41, respectively).ConclusionsPatients’ experiences with the actual level of PCC and the care gap are important for patients’ satisfaction with care.
Dysregulated activation of fetal liver programme in acute liver failure
Authors: Hyun Jeongeun , Oh Seh-Hoon , Premont Richard T , Guy Cynthia D , Berg Carl L , Diehl Anna Mae 
Published: January 2019

ObjectiveUncertainty about acute liver failure (ALF) pathogenesis limits therapy. We postulate that ALF results from excessive reactivation of a fetal liver programme that is induced in hepatocytes when acutely injured livers regenerate. To evaluate this hypothesis, we focused on two molecules with known oncofetal properties in the liver, Yes-associated protein-1 (YAP1) and Insulin-like growth factor-2 RNA-binding protein-3 (IGF2BP3).DesignWe compared normal liver with explanted livers of patients with ALF to determine if YAP1 and IGF2BP3 were induced; assessed whether these factors are upregulated when murine livers regenerate; determined if YAP1 and IGF2BP3 cooperate to activate the fetal programme in adult hepatocytes; and identified upstream signals that control these factors and thereby hepatocyte maturity during recovery from liver injury.ResultsLivers of patients with ALF were massively enriched with hepatocytes expressing IGF2BP3, YAP1 and other fetal markers. Less extensive, transient accumulation of similar fetal-like cells that were proliferative and capable of anchorage-independent growth occurred in mouse livers that were regenerating after acute injury. Fetal reprogramming of hepatocytes was YAP1-dependent and involved YAP1-driven reciprocal modulation of let7 microRNAs and IGF2BP3, factors that negatively regulate each other to control fate decisions in fetal cells. Directly manipulating IGF2BP3 expression controlled the fetal-like phenotype regardless of YAP1 activity, proving that IGF2BP3 is the proximal mediator of this YAP1-directed fate.ConclusionAfter acute liver injury, hepatocytes are reprogrammed to fetal-like cells by a YAP1-dependent mechanism that differentially regulates let7 and IGF2BP3, identifying novel therapeutic targets for ALF.
Violence prevalence and prevention status in China
Authors: Gao Xin , Ye Pengpeng , Er Yuliang , Jin Ye , Wang Linhong , Duan Leilei 
Published: January 2019

ObjectivesTo describe the prevalence status of violence and its prevention in China, and to provide reference for the development of strategies regarding violence prevention.MethodsViolence mortality data between 2006 and 2015 were obtained from the national disease/death surveillance data set in 2006–2015. Data on violence-related medical cases were collected from the 2015 National Injury Surveillance System. The laws and policies about violence prevention and violence prevention programmes in China were described.ResultsViolence mortality declined by 57.02% during 2006–2015 from 1.21/100 000 to 0.52/100 000. Violent death rate in males peaked in the age group 25–29 years (1.05/100 000) and it was low in the age group <15 years. Female violence mortality rate peaked during infancy (0.54/100 000), aged 25–29 (0.53/100 000) and age above 85 (0.98/100 000). The laws and policies about violence prevention were more perfect, while most prevention programmes were limited in scale and duration.ConclusionsThe mortality of violence declined in China during 2006–2015. It is necessary to conduct gender-specific prevention strategies and improve the data collection and prevention service.
Exact wormholes solutions without exotic matter in f(R,T) gravity
Authors: Zubair M. , Saleem Rabia , Ahmad Yasir , Abbas G. 
Published: January 2019

This paper is aimed to evaluate the existence of wormholes in viable [Formula: see text] gravity models (where [Formula: see text] is the scalar curvature and [Formula: see text] is the trace of stress–energy tensor of matter). The exact solutions for energy–momentum tensor components depending on different shapes and redshift functions are calculated without some additional constraints. To investigate this, we consider static spherically symmetric geometry with matter contents as anisotropic fluid and formulate the Einstein field equations for three different [Formula: see text] models. For each model, we derive expression for weak and null energy conditions and graphically analyzed its violation near the throat. It is really interesting that wormhole solutions do not require the presence of exotic matter — like that in general relativity. Finally, the stability of the solutions for each model is presented using equilibrium condition.
Modelling oblique inversion of pre-existing grabens
Authors: Deng Hongling , Koyi Hemin A. , Zhang Jinjiang 
Published: January 2019

Abstract

A series of analogue models were run to investigate oblique inversion of pre-existing grabens when overprinted by later shortening and the effect of these grabens on development of contractional structures. Obliquity angle (
α
) defining the initial trend of pre-existing grabens relative to the shortening direction, was systematically changed from 0°, 10°, 20°, 30°, 40°, 50°, 65° and 90°. Different structural styles are shown in different models and also in sections cutting across different parts of the models. Model results show that existence of multi-grabens enhances lateral discontinuity of overprinted thrusts in map view. With increasing the obliquity angle, more and longer lateral ramps developed sub-parallel to the graben trends. The pre-existing grabens were apparently rotated from their initial trends during shortening. Some of the normal faults bounding the grabens were partially inverted and resulted in bulging of the syn- and post-rift graben fill sediments. Most normal faults were displaced and rotated by thrusting, and provided relatively weak zones for propagation of thrusts. By comparing with observations from Qingxi graben in western China and from the SW Taiwan fold-and-thrust belt, where oblique inversion occurred, model results can be used to interpret unclear relationships between thrusts and pre-existing extensional structures during superimposed deformation.
A Close Look at a Daily Dataset of Malware Samples
Authors: Ugarte-Pedrero Xabier , Graziano Mariano , Balzarotti Davide 
Published: January 2019

The number of unique malware samples is growing out of control. Over the years, security companies have designed and deployed complex infrastructures to collect and analyze this overwhelming number of samples. As a result, a security company can collect more than 1M unique files per day only from its different feeds. These are automatically stored and processed to extract actionable information derived from static and dynamic analysis. However, only a tiny amount of this data is interesting for security researchers and attracts the interest of a human expert.
To the best of our knowledge, nobody has systematically dissected these datasets to precisely understand what they really contain. The security community generally discards the problem because of the alleged prevalence of uninteresting samples.

In this article, we guide the reader through a step-by-step analysis of the hundreds of thousands Windows executables collected in one day from these feeds. Our goal is to show how a company can employ existing state-of-the-art techniques to automatically process these samples and then perform manual experiments to understand and document what is the real content of this gigantic dataset. We present the filtering steps, and we discuss in detail how samples can be grouped together according to their behavior to support manual verification. Finally, we use the results of this measurement experiment to provide a rough estimate of both the human and computer resources that are required to get to the bottom of the
catch of the day
.
Information architects
Authors: Swope Amber 
Published: January 2019

Every organization relies on information to communicate with prospects and customers - blog posts, articles, whitepapers, user manuals, web portals, videos, tweets, social media posts, moderated forums, and more. This means that many people are creating content and are delivering it in multiple ways. To meet our users' needs, we need information architecture (IA) to provide the framework for developing and delivering this information.
Although most content creators do not think of themselves as information architects, many of them perform tasks that are information architecture responsibilities. If you decide what information gets created and delivered, identify keywords to support findability, or organize the hierarchy for a table of contents, you are performing IA tasks. To learn who was performing these tasks and how they ended up with this role, I conducted a survey. This article presents my analysis of the results based upon my experience and relevant industry sources.
A DNA Repair and Cell-Cycle Gene Expression Signature in Primary and Recurrent Glioblastoma: Prognostic Value and Clinical Implications
Authors: Gobin Matthieu , Nazarov Petr V. , Warta Rolf , Timmer Marco , Reifenberger Guido , Felsberg Joerg , Vallar Laurent , Chalmers Anthony J. , Herold-Mende Christel C. , Goldbrunner Roland , Niclou Simone P. , Van Dyck Eric 
Published: January 2019

Abstract

Inevitable tumor recurrence and a poor median survival are frustrating reminders of the inefficacy of our current standard of care for patients with newly diagnosed glioblastoma (GBM), which includes surgery followed by radiotherapy and chemotherapy with the DNA alkylating agent temozolomide. Because resistance to genotoxic damage is achieved mainly through execution of the DNA damage response (DDR) and DNA repair pathways, knowledge of the changes in DNA repair and cell-cycle gene expression that occur during tumor development might help identify new targets and improve treatment. Here, we performed a gene expression analysis targeting components of the DNA repair and cell-cycle machineries in cohorts of paired tumor samples (i.e., biopsies from the same patient obtained at the time of primary tumor operation and at recurrence) from patients treated with radiotherapy or radiotherapy plus temozolomide. We identified and validated a 27-gene signature that resulted in the classification of GBM specimens into three groups, two of which displayed inverse expression profiles. Each group contained primary and recurrent samples, and the tumor at relapse frequently displayed a gene expression profile different from that of the matched primary biopsy. Within the groups that exhibited opposing gene expression profiles, the expression pattern of the gene signature at relapse was linked to progression-free survival. We provide experimental evidence that our signature exposes group-specific vulnerabilities against genotoxicants and inhibitors of the cell cycle and DDR, with the prospect of personalized therapeutic strategies.

Significance: These findings suggest that classification of GBM tumors based on a DNA repair and cell-cycle gene expression signature exposes vulnerabilities to standard-of-care therapies and offers the potential for personalized therapeutic strategies.
An Orally Active Galectin-3 Antagonist Inhibits Lung Adenocarcinoma Growth and Augments Response to PD-L1 Blockade
Authors: Vuong Lynda , Kouverianou Eleni , Rooney Claire M. , McHugh Brian J. , Howie Sarah E.M. , Gregory Christopher D. , Forbes Stuart J. , Henderson Neil C. , Zetterberg Fredrik R. , Nilsson Ulf J. , Leffler Hakon , Ford Paul , Pedersen Anders , Gravelle Lise , Tantawi Susan , Schambye Hans , Sethi Tariq , MacKinnon Alison C. 
Published: January 2019

AbstractA combination therapy approach is required to improve tumor immune infiltration and patient response to immune checkpoint inhibitors that target negative regulatory receptors. Galectin-3 is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and whose expression correlates with poor survival particularly in patients with non–small cell lung cancer (NSCLC). To examine the role of galectin-3 inhibition in NSCLC, we tested the effects of galectin-3 depletion using genetic and pharmacologic approaches on syngeneic mouse lung adenocarcinoma and human lung adenocarcinoma xenografts. Galectin-3−/− mice developed significantly smaller and fewer tumors and metastases than syngeneic C57/Bl6 wild-type mice. Macrophage ablation retarded tumor growth, whereas reconstitution with galectin-3-positive bone marrow restored tumor growth in galectin-3−/− mice, indicating that macrophages were a major driver of the antitumor response. Oral administration of a novel small molecule galectin-3 inhibitor GB1107 reduced human and mouse lung adenocarcinoma growth and blocked metastasis in the syngeneic model. Treatment with GB1107 increased tumor M1 macrophage polarization and CD8+ T-cell infiltration. Moreover, GB1107 potentiated the effects of a PD-L1 immune checkpoint inhibitor to increase expression of cytotoxic (IFNγ, granzyme B, perforin-1, Fas ligand) and apoptotic (cleaved caspase-3) effector molecules. In summary, galectin-3 is an important regulator of lung adenocarcinoma progression. The novel galectin-3 inhibitor presented could provide an effective, nontoxic monotherapy or be used in combination with immune checkpoint inhibitors to boost immune infiltration and responses in lung adenocarcinoma and potentially other aggressive cancers.Significance:A novel and orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and metastasis and augments response to PD-L1 blockade.
GARP Dampens Cancer Immunity by Sustaining Function and Accumulation of Regulatory T Cells in the Colon
Authors: Salem Mohammad , Wallace Caroline , Velegraki Maria , Li Anqi , Ansa-Addo Ephraim , Metelli Alessandra , Kwon Hyunwoo , Riesenberg Brian , Wu Bill , Zhang Yongliang , Guglietta Silvia , Sun Shaoli , Liu Bei , Li Zihai 
Published: January 2019

Abstract

Activated regulatory T (Treg) cells express the surface receptor glycoprotein-A repetitions predominant (GARP), which binds and activates latent TGFβ. How GARP modulates Treg function in inflammation and cancer remains unclear. Here we demonstrate that loss of GARP in Treg cells leads to spontaneous inflammation with highly activated CD4+ and CD8+ T cells and development of enteritis. Treg cells lacking GARP were unable to suppress pathogenic T-cell responses in multiple models of inflammation, including T-cell transfer colitis. GARP−/− Treg cells were significantly reduced in the gut and exhibited a reduction in CD103 expression, a colon-specific migratory marker. In the colitis-associated colon cancer model, GARP on Treg cells dampened immune surveillance, and mice with GARP−/− Treg cells exhibited improved antitumor immunity. Thus, GARP empowers the functionality of Treg cells and their tissue-specific accumulation, highlighting the importance of cell surface TGFβ in Treg function and GARP as a potential therapeutic target for colorectal cancer therapy.

Significance: These findings uncover functions of membrane-bound TGFβ and GARP that tune the activity of Treg cells, highlighting a potential treatment strategy in autoimmune diseases and cancer.
The CD98 Heavy Chain Is a Marker and Regulator of Head and Neck Squamous Cell Carcinoma Radiosensitivity
Authors: Digomann David , Kurth Ina , Tyutyunnykova Anna , Chen Oleg , Löck Steffen , Gorodetska Ielizaveta , Peitzsch Claudia , Skvortsova Ira-Ida , Negro Giulia , Aschenbrenner Bertram , Eisenhofer Graeme , Richter Susan , Heiden Stephan , Porrmann Joseph , Klink Barbara , Schwager Christian , Dowle Adam A. , Hein Linda , Kunz-Schughart Leoni A. , Abdollahi Amir , Lohaus Fabian , Krause Mechthild , Baumann Michael , Linge Annett , Dubrovska Anna 
Published: January 2019

Abstract

Purpose:
The heavy chain of the CD98 protein (CD98hc) is encoded by the SLC3A2 gene. Together with the light subunit LAT1, CD98hc constitutes a heterodimeric transmembrane amino acid transporter. High SLC3A2 mRNA expression levels are associated with poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC) treated with radiochemotherapy. Little is known regarding the CD98hc protein–mediated molecular mechanisms of tumor radioresistance.

Experimental Design:
CD98hc protein expression levels were correlated with corresponding tumor control dose 50 (TCD50) in HNSCC xenograft models. Expression levels of CD98hc and LAT1 in HNSCC cells were modulated by siRNA or CRISPR/Cas9 gene editing. HNSCC cell phenotypes were characterized by transcription profiling, plasma membrane proteomics, metabolic analysis, and signaling pathway activation. Expression levels of CD98hc and LAT1 proteins were examined by IHC analysis of tumor tissues from patients with locally advanced HNSCC treated with primary radiochemotherapy (RCTx). Primary endpoint was locoregional tumor control (LRC).

Results:
High expression levels of CD98hc resulted in an increase in mTOR pathway activation, amino acid metabolism, and DNA repair as well as downregulation of oxidative stress and autophagy. High expression levels of CD98hc and LAT1 proteins were significantly correlated and associated with an increase in radioresistance in HNSCC in vitro and in vivo models. High expression of both proteins identified a poor prognosis subgroup in patients with locally advanced HNSCC after RCTx.

Conclusions:
We found that CD98hc-associated signaling mechanisms play a central role in the regulation of HNSCC radioresistance and may be a promising target for tumor radiosensitization.
Maternal Embryonic Leucine Zipper Kinase (MELK), a Potential Therapeutic Target for Neuroblastoma
Authors: Chlenski Alexandre , Park Chanyoung , Dobratic Marija , Salwen Helen R. , Budke Brian , Park Jae-Hyun , Miller Ryan , Applebaum Mark A. , Wilkinson Emma , Nakamura Yusuke , Connell Philip P. , Cohn Susan L. 
Published: January 2019

Abstract
Maternal embryonic leucine zipper kinase (MELK) activates pathways that mediate aggressive tumor growth and therapy resistance in many types of adult cancers. Pharmacologic and genomic inhibition of MELK impairs tumor growth and increases sensitivity to radiation and chemotherapy. On the basis of these promising preclinical studies, early-phase adult clinical trials testing the MELK inhibitor OTS167 are ongoing. To investigate whether MELK is also a therapeutic target in neuroblastoma, we analyzed MELK expression in primary tumors and cell lines, and examined the effects of OTS167 on neuroblastoma growth. In primary tumors, high levels of MELK were associated with advanced stage disease and inferior survival. Higher levels of MELK were also detected in tumorigenic versus nontumorigenic neuroblastoma cell lines, and cells with higher levels of MELK expression were more sensitive to OTS167 than low-MELK expressing cells. OTS167 suppressed the growth of neuroblastoma xenografts, and in a preclinical model of minimal residual disease, survival was prolonged with MELK inhibition. OTS167 treatment downregulated MELK and its target enhancer of zeste homolog 2 (EZH2), a component of the polycomb repressive complex 2 (PRC2) that is known to modulate the DNA damage response. We also show that OTS167 reduced the formation of collapsed replication forks induced by camptothecin or radiation. Taken together, our results indicate that MELK indirectly mediates efficient processing of replication-associated DNA lesions in neuroblastoma, and that OTS167 sensitizes cells to DNA-damaging agents by abrogating this process. Further studies evaluating the activity of combination treatment regimens with OTS167 in neuroblastoma are warranted.