bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor aggression among hepatitis-C related hepatocellular carcinoma patients: an observational study regarding the impact of anti-HCV therapy
Authors: Khalid Javeria , Umar Mohammad , Ur-Rehman Tofeeq , Ali Mashhood , Khan Gul Majid 
Published: May 2020

Abstract
Background
Hepatitis C virus (HCV) represents a major risk factor for hepatocellular carcinoma (HCC) development and anti-HCV therapy is a significant measure to reduce the incidence of HCC, however development of HCC in HCV treated patients is an emerging clinical problem which needs to be investigated. In this study we aim to analyze association between anti-HCV therapy and tumor pattern of HCV related HCC patients.

Methods
Hepatocellular Carcinoma (HCC) patients with seropositivity for hepatitis C virus (HCV) antibodies, registered at three tertiary care hospitals of Rawalpindi and Islamabad, Pakistan during August 2017 to July 2018 were enrolled. Selected patients were then segregated in two groups on the basis of their HCV treatment history i.e., “TN” (HCV Treatment Naïve i.e. having no history/medical record for treatment prior to HCC diagnosis) and “TH” (Treated for HCV infection). Aggressiveness index (AgI) scoring system was applied to determine the tumor pattern. Univariate and multivariate analysis was carried out to analyze the independent effect of anti-HCV therapy on tumor pattern.

Results
Out of 234 consecutive HCC patients, 171 HCV-related HCC patients were enrolled in final analysis and labeled as “TN” (n = 120) and “TH” (n = 51). Tumor pattern was found to be significantly aggressive (P = 0.02) in the treated cohort with an adjusted odds of 2.47 for aggressive and 6.92 for highly aggressive tumor. Neutrophil to lymphocyte ratio (NLR) was strongly associated with highly aggressive tumor pattern (P = 0.012). Patients in TN group were found to be marginally older than those in the TH group (59.5 vs. 55 years) where mean age of the patients treated with direct acting anti-viral agents was found to be visibly lower than mean age of patients who received interferon based treatment (53.5 vs. 57 years) with significant masculine predominance (62.1 vs. 37.9%, P = 0.049).

Conclusion
We observed raised neutrophil to lymphocyte ratio and prominence of younger age with aggressive tumor biology in HCV treated HCC patients. These observations highlight the need for a longitudinal prospective study on HCV positive subjects treated with antivirals, irrespective of treatment response.
Investigating the delivery of health and nutrition interventions for women and children in conflict settings: a collection of case studies from the BRANCH Consortium
Authors: Ataullahjan Anushka , Gaffey Michelle F. , Sami Samira , Singh Neha S. , Tappis Hannah , Black Robert E. , Blanchet Karl , Boerma Ties , Langer Ana , Spiegel Paul B. , Waldman Ronald J. , Wise Paul H. , Bhutta Zulfiqar A. 
Published: May 2020

AbstractGlobally, the number of people affected by conflict is the highest in history, and continues to steadily increase. There is currently a pressing need to better understand how to deliver critical health interventions to women and children affected by conflict. The compendium of articles presented in this Conflict and Health Collection brings together a range of case studies recently undertaken by the BRANCH Consortium (Bridging Research & Action in Conflict Settings for the Health of Women and Children). These case studies describe how humanitarian actors navigate and negotiate the multiple obstacles and forces that challenge the delivery of health and nutrition interventions for women, children and adolescents in conflict-affected settings, and to ultimately provide some insight into how service delivery can be improved.
Pathological alterations in striatal compartments in the human brain of autism spectrum disorder
Authors: Kuo Hsiao-Ying , Liu Fu-Chin 
Published: May 2020

AbstractThe striatum comprises a mosaic structure of striosomal and matrix compartments. Imbalanced neuronal activity between striosomes and matrix is implicated in neurological deficits in psychomotor and limbic functions. Because patients with autism spectrum disorder (ASD) are impaired in social communication and psychomotor function, it raises the possibility that abnormal striatal compartments may contribute to ASD pathogenesis. Here, we provide pathological evidence from human postmortem brains to support this hypothesis. Because ASD is a neurodevelopmental disease that emerges early in childhood, we analyzed juvenile and adolescent brains. Distinct patterns ofPRODYNORPHIN-positive and calbindin-poor striosomes were detected in the caudate nucleus of control brains by in situ hybridization and immunohistochemistry. By contrast,PRODYNORPHIN-positive and calbindin-poor striosomes were decreased in the caudate nucleus of young ASD brains. Moreover, calbindin, a matrix marker, was aberrantly increased in the striosomal compartment, obscuring the boundaries between calbindin-poor striosomes and calbindin-rich matrix in ASD caudate nucleus. Calbindin-positive cells were decreased in the ASD matrix compartment. Collectively, our study has uncovered for the first time that aberrant striatal compartments occur in the caudate nucleus of human ASD brains, which suggests abnormal striatal compartmentation as a pathological signature that has previously been underestimated in ASD pathogenesis.
The recurrent SETBP1 c.2608G > A, p.(Gly870Ser) variant in a patient with Schinzel-Giedion syndrome: an illustrative case of the utility of whole exome sequencing in a critically ill neonate
Authors: Leone Maria Pia , Palumbo Pietro , Palumbo Orazio , Di Muro Ester , Chetta Massimiliano , Laforgia Nicola , Resta Nicoletta , Stella Alessandro , Castellana Stefano , Mazza Tommaso , Castori Marco , Carella Massimo , Bukvic Nenad 
Published: May 2020

Abstract
Background
Schinzel-Giedion syndrome (SGS) is a multiple malformation syndrome mainly characterized by severe intellectual disability, distinctive facial features, and multiple congenital anomalies, including skeletal abnormalities, genitourinary and renal malformations, cardiac defects, as well as an increased pediatric cancer risk. Recently, SGS has been associated with de novo heterozygous deleterious variants in the SETBP1 gene; to date, nine different variants, clustering in exon 4 of SETBP1, have been identified in 25 patients.

Case presentation
In this study, by using Whole Exome Sequencing (WES), we identified a patient with a recurrent missense mutation in SETBP1, the c.2608G > A, p.(Gly870Ser) variant, previously reported as likely pathogenic. This finding allowed us to confirm the suspected clinical diagnosis of SGS. Clinical features of patients carrying the same variant, including our patient, were evaluated by a review of medical records.

Conclusions
Our study confirms SGS as a severe disorder potentially presenting at birth as a critically ill neonate and demonstrates the causal role of the c.2608G > A, p.(Gly870Ser) variant in the etiology of the syndrome. Moreover, although the cohort of SETBP1-patients reported in the literature is still small, our study reports for the first time the prevalence of the variant (about 27%, 7/26). Finally, given the heterogeneity of clinical presentations of affected patients hospitalized in Neonatal Intensive Care Units (NICU) and/or Pediatric Intensive Care Units (PICU), in agreement with emerging data from the literature, we suggest that WES should be used in the diagnosis of unexplained syndromic conditions, and even as part of a standard first-line diagnostic approach, as it would allow a better diagnosis, counseling and management of affected patients and their families.
Core outcome set measurement for future clinical trials in acute myeloid leukemia: the HARMONY study protocol using a multi-stakeholder consensus-based Delphi process and a final consensus meeting
Authors: Lang Katharina M. , Harrison Kathryn L. , Williamson Paula R. , Huntly Brian J. P. , Ossenkoppele Gert , Geissler Jan , Bereczky Tamàs , Hernández-Rivas Jesús M. , Chevrou-Séverac Hélène , Goodbody Rory , Schulze-Rath Renate , Bullinger Lars 
Published: May 2020

Abstract
Background
Acute myeloid leukemia (AML) is the most common acute leukemia in adults and has an unacceptably low cure rate. In recent years, a number of new treatment strategies and compounds were developed for the treatment of AML. There were several randomized controlled clinical trials with the objective to improve patients’ management and patients’ outcome in AML. Unfortunately, these trials are not always directly comparable since they do not measure the same outcomes, and currently there are no core outcome sets that can be used to guide outcome selection and harmonization in this disease area. The HARMONY (Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms in Hematology) Alliance is a public-private European network established in 2017 and currently includes 53 partners and 32 associated members from 22 countries. Amongst many other goals of the HARMONY Alliance, Work Package 2 focuses on defining outcomes that are relevant to each hematological malignancy. Accordingly, this pilot study will be performed to define a core outcome set in AML.

Methods
The pilot study will use a three-round Delphi survey and a final consensus meeting to define a core outcome set. Participants will be recruited from different stakeholder groups, including patients, clinicians, regulators and members of the European Federation of Pharmaceutical Industries and Associations. At the pre-Delphi stage, a literature research was conducted followed by several semi-structured interviews of clinical public and private key opinion leaders. Subsequently, the preliminary outcome list was discussed in several multi-stakeholder face-to-face meetings. The Delphi survey will reduce the preliminary outcome list to essential core outcomes. After completion of the last Delphi round, a final face-to-face meeting is planned to achieve consensus about the core outcome set in AML.

Discussion
As part of the HARMONY Alliance, the pilot Delphi aims to define a core outcome set in AML on the basis of a multi-stakeholder consensus. Such a core outcome set will help to allow consistent comparison of future clinical trials and real-world evidence research and ensures that appropriate outcomes valued by a range of stakeholders are measured within future trials.
Taf14 is required for the stabilization of transcription pre-initiation complex in Saccharomyces cerevisiae
Authors: Peil Kadri , Jürgens Henel , Luige Johanna , Kristjuhan Kersti , Kristjuhan Arnold 
Published: May 2020

Abstract
Background
The YEATS domain is a highly conserved protein structure that interacts with acetylated and crotonylated lysine residues in N-terminal tails of histones. The budding yeast genome encodes three YEATS domain proteins (Taf14, Yaf9, and Sas5) that are all the subunits of different complexes involved in histone acetylation, gene transcription, and chromatin remodeling. As the strains deficient in all these three genes are inviable, it has been proposed that the YEATS domain is essential in yeast. In this study we investigate in more detail the requirement of YEATS domain proteins for yeast survival and the possible roles of Taf14 YEATS domain in the regulation of gene transcription.

Results
We found that YEATS domains are not essential for the survival of Saccharomyces cerevisiae cells. Although the full deletion of all YEATS proteins is lethal in yeast, we show that the viability of cells can be restored by the expression of the YEATS-less version of Taf14 protein. We also explore the in vivo functions of Taf14 protein and show that the primary role of its YEATS domain is to stabilize the transcription pre-initiation complex (PIC). Our results indicate that Taf14-mediated interactions become crucial for PIC formation in rpb9Δ cells, where the recruitment of TFIIF to the PIC is hampered. Although H3 K9 residue has been identified as the interaction site of the Taf14 YEATS domain in vitro, we found that it is not the only interaction target in vivo.

Conclusions
Lethality of YEATS-deficient cells can be rescued by the expression of truncated Taf14 protein lacking the entire YEATS domain, indicating that the YEATS domains are not required for cell survival. The YEATS domain of Taf14 participates in PIC stabilization and acetylated/crotonylated H3K9 is not the critical target of the Taf14 YEATS domain in vivo.
The Alzheimer’s Prevention Initiative Composite Cognitive Test: a practical measure for tracking cognitive decline in preclinical Alzheimer’s disease
Authors: Langbaum Jessica B. , Ellison Noel N. , Caputo Angelika , Thomas Ronald G. , Langlois Carolyn , Riviere Marie-Emmanuelle , Graf Ana , Lopez Lopez Cristina , Reiman Eric M. , Tariot Pierre N. , Hendrix Suzanne B. 
Published: May 2020

Abstract
Background
There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer’s disease (AD) treatment trials. We reported previously a composite cognitive test score sensitive to tracking preclinical AD decline up to 5 years prior to clinical diagnosis. Here we expand upon and refine this work, empirically deriving a composite cognitive test score sensitive to tracking preclinical AD decline up to 11 years prior to diagnosis and suitable for use as a primary endpoint in a preclinical AD trial.

Methods
This study used a longitudinal approach to maximize sensitivity to tracking progressive cognitive decline in people who progressed to the clinical stages of AD (n = 868) compared to those who remained cognitively unimpaired during the same time period (n = 989), thereby correcting for normal aging and practice effects. Specifically, we developed the Alzheimer’s Prevention Initiative Preclinical Composite Cognitive test (APCC) to measure very early longitudinal cognitive decline in older adults with preclinical AD. Data from three cohorts from Rush University were analyzed using a partial least squares (PLS) regression model to identify optimal composites within different time periods prior to diagnosis, up to 11 years prior to diagnosis. The mean-to-standard deviation ratio (MSDRs) is an indicator of sensitivity to change and was used to inform the final calculation of the composite score.

Results
The optimal composite, the APCC, is calculated: 0.26*Symbol Digit Modalities + 2.24*MMSE Orientation to Time + 2.14*MMSE Orientation to Place + 0.53*Logical Memory Delayed Recall + 1.36* Word List-Delayed Recall + 0.68*Judgment of Line Orientation + 1.39*Raven’s Progressive Matrices Matrices (subset of 9 items from A and B). The MSDR of the APCC in a population of preclinical AD individuals who eventually progress to cognitive impairment, compared to those who remained cognitively unimpaired during the same time period, was − 1.10 over 1 year.

Conclusions
The APCC is an empirically derived composite cognitive test score with high face validity that is sensitive to preclinical AD decline up to 11 years prior to diagnosis of the clinical stages of AD. The components of the APCC are supported by theoretical understanding of cognitive decline that occurs during preclinical AD. The APCC was used as a primary outcome in the API Generation Program trials.
Hereditary angioedema C1-esterase inhibitor replacement therapy and coexisting autoimmune disorders: findings from a claims database
Authors: Farkas Henriette , Levy Donald , Supina Dylan , Berger Melvin , Prusty Subhransu , Fridman Moshe 
Published: May 2020

AbstractIn this letter to the editor, we present results of claims data analysis. This claims data analysis supports a hypothesis that in patients with hereditary angioedema due to C1-esterase inhibitor (C1-INH) deficiency, the occurrence and/or symptomatology of coexisting autoimmune disease may be positively influenced by a replacement therapy with plasma derived C1-INH.
Existence of a strong solution to moist atmospheric equations with the effects of topography
Authors: Lian Ruxu , Ma Jieqiong 
Published: May 2020

AbstractIn this paper, we consider the primitive three-dimensional viscous equations for large-scale atmosphere dynamics with topography effects and water vapor phase transition process. This modified climate model is commonly used in weather and climate predictions, and few theoretical analyses have been performed on them. The existence and uniqueness of a global strong solution to this climate model is established based on the initial data assumptions.
Stability and bifurcation analysis in a single-species stage structure system with Michaelis–Menten-type harvesting
Authors: Yu Xiangqin , Zhu Zhenliang , Lai Liyun , Chen Fengde 
Published: May 2020

AbstractIn this paper, we prpose a single-species stage structure model with Michaelis–Menten-type harvesting for mature population. We investigate the existence of all possible equilibria of the system and discuss the stability of equilibria. We use Sotomayor’s theorem to derive the conditions for the existence of saddle-node and transcritical bifurcations. From the ecological point of view, we analyze the effect of harvesting on the model of mature population and consider it as a bifurcation parameter, giving the maximum threshold of continuous harvesting. By constructing a Lyapunov function and Bendixson–Dulac discriminant, we give sufficient conditions for the global stability of boundary equilibrium and positive equilibrium, respectively. Our study shows that nonlinear harvesting may lead to a complex dynamic behavior of the system, which is quite different from linear harvesting. We carry out numeric simulations to verify the feasibility of the main results.
Rattlesnake migrations and the implications of thermal landscapes
Authors: Harvey Jessica A. , Larsen Karl W. 
Published: May 2020

Abstract
Background
The importance of thermal resources to terrestrial ectotherms has been well documented but less often considered in larger-scale analyses of habitat use and selection, such as those routinely conducted using standard habitat features such as vegetation and physical structure. Selection of habitat based on thermal attributes may be of particular importance for ectothermic species, especially in colder climates. In Canada, Western Rattlesnakes (Crotalus oreganus) reach their northern limits, with limited time to conduct annual migratory movements between hibernacula and summer habitat. We radio-tracked 35 male snakes departing from 10 different hibernacula. We examined coarse-scale differences in migratory movements across the region, and then compared the route of each snake with thermal landscapes and ruggedness GIS maps generated for different periods of the animals’ active season.

Results
We observed dichotomous habitat use (grasslands versus upland forests) throughout most of the species’ northern range, reflected in different migratory movements of male snakes emanating from different hibernacula. Snakes utilizing higher-elevation forests moved further during the course of their annual migrations, and these snakes were more likely to use warmer areas of the landscape.

Conclusion
In addition to thermal benefits, advantages gained from selective migratory patterns may include prey availability and outbreeding. Testing these alternative hypotheses was beyond the scope of this study, and to collect the data to do so will require overcoming certain challenges. Still, insight into migratory differences between rattlesnake populations and the causal mechanism(s) of migrations will improve our ability to assess the implications of landscape change, management, and efficacy of conservation planning. Our findings suggest that such assessments may need to be tailored to individual dens and the migration strategies of their inhabitants. Additionally, local and landscape-scale migration patterns, as detected in this study, will have repercussions for snakes under climate-induced shifts in ecosystem boundaries and thermal regimes.
Pharmacist intervention amid the coronavirus disease 2019 (COVID-19) pandemic: from direct patient care to telemedicine
Authors: Elbeddini Ali , Yeats Aniko 
Published: May 2020

Abstract
Introduction
The coronavirus disease (COVID-19) pandemic has placed enormous pressures on the Canadian healthcare system. Patients are expected to stay home in order to contain the spread of the virus, but understandably have numerous questions and concerns about their health. With physical distancing being of utmost importance during the pandemic, much of healthcare has been forced to move online or over the telephone. Virtual healthcare, in the form of video calls, email, or telephone calls with patients, can significantly enhance access to healthcare. Many clinics have moved their appointments online, and physicians are seeing their patients by means of online video calls. Similarly, patients are refilling their prescriptions online and calling pharmacists whenever they have questions about their medications or medical conditions. Pharmacists are considered the most accessible primary care providers, so it is crucial for patients to know that pharmacists are there to support them throughout the pandemic.
Three-dimensional topographic relief of the oceanic crust may control the occurrence of shallow very-low-frequency earthquakes in the Nankai Trough off Kumano
Authors: Shiraishi Kazuya , Yamada Yasuhiro , Nakano Masaru , Kinoshita Masataka , Kimura Gaku 
Published: May 2020

AbstractTo explore a local relationship between geological structures and the occurrence of very-low-frequency earthquakes (VLFEs), a particular class of slow earthquakes with characteristic periods of 10–100 s, we investigated three-dimensional (3D) structural features using reprocessed 3D seismic data from the Nankai Trough off Kumano, southwestern Japan. In this region, VLFEs have been observed along the subducting Philippine Sea Plate. Although the detailed source distribution of VLFEs was estimated by means of recent land-based and offshore seismic networks, the relation with geological features is not well understood. First, we reprocessed the 3D seismic data with advanced techniques and reinterpreted the fault distribution in the sediment layer of the accretionary prism and tracked two key horizons: a décollement and the oceanic crust surface. In the accretionary prism sediments, multiple continuous reflectors of basal detachments in the underthrust sequence and conjugate faults cutting the shallow imbricated thrust sequence were identified. In contrast to the gentle variation in the décollement surface, the topographic relief of the oceanic crust was prominent, with ridges and surface displacement due to faults in the oceanic crust. Then, we compared the structural features with the VLFE source locations. Most VLFEs were located deep in the underthrust sediments where the sediments may consist of underconsolidated muds. Furthermore, a high spatial correlation was observed between the VLFE distribution and the oceanic crust topographic relief. The maximum stress direction, which was inferred from the conjugate faults in the imbricated thrust zone, was consistent with the spatial relation between the VLFE localization and the oceanic crust central ridge. Oceanic crust ridges may cause strain accumulation in the underthrust sediments on the landward sides of the ridges, and low-angle slow thrust movements might be caused using weak slip planes in the underthrust muddy sediments. That is, the topographic relief of the oceanic crust may control the occurrence of shallow VLFEs in the Nankai Trough.