bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult and pediatric mechanical circulation: a guide for the hematologist
Authors: Kreuziger Lisa Baumann , Massicotte M. Patricia 
Published: April 2019

AbstractMechanical circulatory support (MCS) is the overarching term that encompasses the temporary and durable devices used in patients with severe heart failure. MCS disturbs the hematologic and coagulation system, leading to platelet activation, activation of the contact pathway of coagulation, and acquired von Willebrand syndrome. Ischemic stroke and major hemorrhage occur in up to 30% of patients. Hematologists are an essential part of the MCS team because they understand the delicate balance between bleeding and clotting and alteration of hemostasis with antithrombotic therapy. However, prior to this important collaborative role, learning the terminology used in the field and types of MCS devices allows improved communication with the MCS team and best patient care. Understanding which antithromobotic therapies are used at baseline is also required to provide recommendations if hemorrhage or thrombosis occurs. Additional challenging consultations in MCS patients include the influence of thrombophilia on the risk for thrombosis and management of heparin-induced thrombocytopenia. This narrative review will provide a foundation to understand MCS devices how to prevent, diagnose, and manage MCS thrombosis for the practicing hematologist.
Beyond plasma exchange: novel therapies for thrombotic thrombocytopenic purpura
Authors: Dane Kathryn , Chaturvedi Shruti 
Published: April 2019

AbstractThe advent of plasma exchange has dramatically changed the prognosis of acute thrombotic thrombocytopenic purpura (TTP). Recent insights into TTP pathogenesis have led to the development of novel therapies targeting pathogenic anti-ADAMTS13 antibody production, von Willebrand factor (VWF)–platelet interactions, and ADAMTS13 replacement. Retrospective and prospective studies have established the efficacy of rituximab as an adjunct to plasma exchange for patients with acute TTP, either upfront or for refractory disease. Relapse prevention is a major concern for survivors of acute TTP, and emerging data support the prophylactic use of rituximab in patients with persistent or recurrent ADAMTS13 deficiency in clinical remission. Capalcizumab, a nanobody directed against domain A1 of VWF that prevents the formation of VWF–platelet aggregates, recently completed phase 2 (TITAN) and 3 (HERCULES) trials with encouraging results. Compared with placebo, caplacizumab shortened the time to platelet recovery and may protect against microthrombotic tissue injury in the acute phase of TTP, though it does not modify the underlying immune response. Other promising therapies including plasma cell inhibitors (bortezomib), recombinant ADAMTS13, N-acetyl cysteine, and inhibitors of the VWF–glycoprotein Ib/IX interaction (anfibatide) are in development, and several of these agents are in prospective clinical studies to evaluate their efficacy and role in TTP. In the coming years, we are optimistic that novel therapies and international collaborative efforts will usher in even more effective, evidence-based approaches to address refractory acute TTP and relapse prevention.
Shifting ground and gaps in transfusion support of patients with hematological malignancies
Authors: Cserti-Gazdewich Christine 
Published: April 2019

AbstractThe transfusion support of hematological malignancies considers 2 dimensions: the quantity of what we order (in terms of triggers, doses, targets, and intervals), and the special qualities thereof (with respect to depths of matching and appropriate product modifications). Meanwhile, transfusion-related enhancements in the quantity and quality of life may not be dose dependent but rather tempered by unintended patient harms and system strains from overexposure. Evidence and guidelines concur in endorsing clinically noninferior conservative red blood cell (RBC) transfusion care strategies (eg, triggering at hemoglobin <7-8 g/dL and in single-unit doses for stable, nonbleeding inpatients). However, the unique subpopulation of patients with hematological malignancies who are increasingly managed on an outpatient basis, and striving at least as much for quality of life as quantity of life, is left on the edges of these recommendations, with more questions than answers. If a sufficiently specific future wave of evidence can satisfy the concerns (and contest the assumptions) of the remaining proponents of liberalism, and if conservatism is broadly adopted, savings may be potentially immense. These savings can then be reinvested to address other gaps and inconsistencies in RBC transfusion care, such as the best achievable degrees of prophylactic antigen matching that can minimize alloimmunization-related service delays and reactions.
Evidence-based management of immune thrombocytopenia: ASH guideline update
Authors: Neunert Cindy E. , Cooper Nichola 
Published: April 2019

AbstractIn 1996 and 2011, the American Society of Hematology (ASH) supported efforts to create guidelines for the diagnosis and management of patients with immune thrombocytopenia (ITP). These guidelines used different approaches to arrive at recommendations for testing and treatment. Despite differences in methodology, in both cases there was a paucity of randomized trials to inform recommendations. As data on the diagnosis and management of ITP expands, the ASH Committee on Quality is dedicated to maintaining updated guidelines representing recent evidence and guideline methodology. Here, we will review the updated ASH guidelines on ITP with a focus on recommendations with new understanding and future research to close knowledge gaps.
TACO and TRALI: biology, risk factors, and prevention strategies
Authors: Roubinian Nareg 
Published: April 2019

AbstractTransfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion-related morbidity and mortality. These adverse events are characterized by acute pulmonary edema within 6 hours of a blood transfusion and have historically been difficult to study due to underrecognition and nonspecific diagnostic criteria. However, in the past decade, in vivo models and clinical studies utilizing active surveillance have advanced our understanding of their epidemiology and pathogenesis. With the adoption of mitigation strategies and patient blood management, the incidence of TRALI and TACO has decreased. Continued research to prevent and treat these severe cardiopulmonary events is focused on both the blood component and the transfusion recipient.
Total body irradiation dose and risk of subsequent neoplasms following allogeneic hematopoietic cell transplantation
Authors: Baker K. Scott , Leisenring Wendy M. , Goodman Pamela J. , Ermoian Ralph P. , Flowers Mary E. , Schoch G. , Storb Rainer , Sandmaier Brenda M. , Deeg H. Joachim 
Published: April 2019

Abstract
We examined the impact of total body irradiation (TBI) dose and fractionation on risk of subsequent malignant neoplasms (SMNs) in the era of reduced-intensity and nonmyeloablative conditioning regimens for hematopoietic cell transplantation (HCT). Among 4905 1-year survivors of allogeneic HCT for hematologic malignancies (N = 4500) or nonmalignant disorders (N = 405) who received transplants between 1969 and 2014, we identified 581 SMNs (excluding squamous and basal cell of skin) in 499 individuals. With a median length of follow-up of 12.5 years, the cumulative incidence of SMNs by 30 years after HCT was 22.0%. Compared with age-, sex-, and calendar year–matched Surveillance, Epidemiology, and End Results (SEER) population rates, the standardized incidence ratio (SIR) of SMNs was increased 2.8-fold. The highest SIRs were for SMNs of bones (SIR, 28.8), oral cavity (SIR, 13.8), skin (SIR, 7.3), central nervous system (SIR, 6.0), and endocrine organs (SIR, 4.9). The highest excess absolute risks (EARs) were seen with breast cancer (EAR, 2.2) and cancers of the oral cavity (EAR, 1.5) and skin (EAR, 1.5) per 1000 person-years. The highest incidence of SMNs was in survivors exposed to unfractionated (600-1000 cGy) or high-dose fractionated (1440-1750 cGy) TBI. For patients receiving low-dose TBI, the incidence was comparable to myeloablative chemotherapy alone, although still twofold higher than in the general population. These data demonstrate a strong effect of TBI dose, dose fractionation, and risk of SMNs after HCT. The cumulative incidence of SMNs increases with follow-up time; thus, HCT survivors require lifetime monitoring for early detection and effective therapy of SMNs.
Development of Effective Therapeutics Targeting HER3 for Cancer Treatment
Authors: Liu Xiaolong , Liu Shuang , Lyu Hui , Riker Adam I. , Zhang Yamin , Liu Bolin 
Published: April 2019

AbstractHER3 is the third member of the human epidermal growth factor receptor (HER/EGFR) family, and unlike its other family members, is unique due to its minimal intrinsic kinase activity. As a result, HER3 has to interact with another receptor tyrosine kinase (RTK), such as EGFR or HER2, in order to activate the PI-3 K/Akt, MEK/MAPK, Jak/Stat pathways, as well as Src kinase. Over-expression of HER3 in various human cancers promotes tumor progression by increasing metastatic potential and acting as a major cause of treatment failure. Effective inhibition of HER3, and/or the key downstream mediators of HER3 signaling, is thought to be required to overcome resistance and enhance therapeutic efficacy. To date, there is no known HER3-targeted therapy that is approved for breast cancer, with a number of anti-HER3 antibodies current in various stages of development and clinical testing. Recent data suggests that the epigenetic strategy of using a histone deacetylase (HDAC) inhibitor, or functional cooperative miRNAs, may be an effective way to abrogate HER3 signaling. Here, we summarize the latest advances in our understanding of the mechanism of HER3 signaling in tumor progression, with continuing research towards the identification of therapeutic anti-HER3 antibodies. We will also examine the potential to develop novel epigenetic approaches that specifically target the HER3 receptor, along with important key downstream mediators that are involved in cancer treatment.
Impaired Fat Oxidation During Exercise in Long-Chain Acyl-CoA Dehydrogenase Deficiency Patients and Effect of IV-Glucose
Authors: Madsen Karen Lindhardt , Stemmerik Mads Godtfeldt , Buch Astrid Emilie , Poulsen Nanna Scharff , Lund Allan Meldgaard , Vissing John 
Published: April 2019

AbstractContextLong-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHADD) affects oxidation of long-chain fatty acids (FAO) and is associated with risk of metabolic crises and episodic rhabdomyolysis.Case DescriptionWe present the cases of two patients with LCHADD. Patient 1 (male, 26 years old) was severely affected by muscle weakness and neuropathy. He was diagnosed at age 20 years and was nonadherent to standard dietary management. MRI revealed significant fat replacement of muscle in both calves. Patient 2 (female, 15 years old) was diagnosed at age 1 year. She had no muscle weakness and was compliant with the recommended diet. Compared with healthy persons, both patients had reduced FAO and palmitate oxidation, measured with indirect calorimetry and stable isotope technique during a submaximal cycle ergometer test. Patient 2 had some residual capacity to increase FAO and a compensatory higher carbohydrate oxidation, which ensured a near-normal exercise capacity. Patient 1 was unable to increase FAO and could only complete 23 minutes of exercise, vs 60 minutes by patient 2 and healthy persons. In both, 10% IV infusion of glucose (IV-glucose) during exercise increased carbohydrate oxidation slightly, but endurance was not improved, which likely relates to the fixed weakness in patient 1 and because the residual FAO was suppressed by the glucose infusion in both.ConclusionThe two patients illustrate that FAO is impaired and carbohydrate oxidation is elevated during exercise in patients affected by LCHADD, compared with healthy persons, but IV-glucose has no beneficial effect on exercise tolerance in LCHADD.
Biologically inspired approaches to enhance human organoid complexity
Authors: Holloway Emily M. , Capeling Meghan M. , Spence Jason R. 
Published: April 2019

ABSTRACT
Organoids are complex three-dimensional in vitro organ-like model systems. Human organoids, which are derived from human pluripotent stem cells or primary human donor tissue, have been used to address fundamental questions about human development, stem cell biology and organ regeneration. Focus has now shifted towards implementation of organoids for biological discovery and advancing existing systems to more faithfully recapitulate the native organ. This work has highlighted significant unknowns in human biology and has invigorated new exploration into the cellular makeup of human organs during development and in the adult – work that is crucial for providing appropriate benchmarks for organoid systems. In this Review, we discuss efforts to characterize human organ cellular complexity and attempts to make organoid models more realistic through co-culture, transplantation and bioengineering approaches.
The transmembrane protein Crb2a regulates cardiomyocyte apicobasal polarity and adhesion in zebrafish
Authors: Jiménez-Amilburu Vanesa , Stainier Didier Y. R. 
Published: April 2019

ABSTRACT
Tissue morphogenesis requires changes in cell-cell adhesion as well as in cell shape and polarity. Cardiac trabeculation is a morphogenetic process essential for forming a functional ventricular wall. Here, we show that zebrafish hearts lacking Crb2a, a component of the Crumbs polarity complex, display compact wall integrity defects and fail to form trabeculae. Crb2a localization is very dynamic at a time when other cardiomyocyte junctional proteins also relocalize. Before the initiation of cardiomyocyte delamination to form the trabecular layer, Crb2a is expressed in all ventricular cardiomyocytes and colocalizes with the junctional protein ZO-1. Subsequently, Crb2a becomes localized all along the apical membrane of compact layer cardiomyocytes and is downregulated in the delaminating cardiomyocytes. We show that blood flow and Nrg/ErbB2 signaling regulate Crb2a localization dynamics. crb2a−/− display a multilayered wall with polarized cardiomyocytes: a unique phenotype. Our data further indicate that Crb2a regulates cardiac trabeculation by controlling the localization of tight and adherens junction proteins in cardiomyocytes. Importantly, transplantation data show that Crb2a controls CM behavior in a cell-autonomous manner in the sense that crb2a−/− cardiomyocytes transplanted into wild-type animals were always found in the trabecular layer. In summary, our study reveals a crucial role for Crb2a during cardiac development.
Shigella MreB promotes polar IcsA positioning for actin tail formation
Authors: Krokowski Sina , Atwal Sharanjeet , Lobato-Márquez Damián , Chastanet Arnaud , Carballido-López Rut , Salje Jeanne , Mostowy Serge 
Published: April 2019

ABSTRACT
Pathogenic Shigella bacteria are a paradigm to address key issues of cell and infection biology. Polar localisation of the Shigella autotransporter protein IcsA is essential for actin tail formation, which is necessary for the bacterium to travel from cell-to-cell; yet how proteins are targeted to the bacterial cell pole is poorly understood. The bacterial actin homologue MreB has been extensively studied in broth culture using model organisms including Escherichia coli, Bacillus subtilis and Caulobacter crescentus, but has never been visualised in rod-shaped pathogenic bacteria during infection of host cells. Here, using single-cell analysis of intracellular Shigella, we discover that MreB accumulates at the cell pole of bacteria forming actin tails, where it colocalises with IcsA. Pharmacological inhibition of host cell actin polymerisation and genetic deletion of IcsA is used to show, respectively, that localisation of MreB to the cell poles precedes actin tail formation and polar localisation of IcsA. Finally, by exploiting the MreB inhibitors A22 and MP265, we demonstrate that MreB polymerisation can support actin tail formation. We conclude that Shigella MreB promotes polar IcsA positioning for actin tail formation, and suggest that understanding the bacterial cytoskeleton during host–pathogen interactions can inspire development of new therapeutic regimes for infection control.
This article has an associated First Person interview with the first author of the paper.
Small for gestational age babies and depressive symptoms of mothers during pregnancy: Results from a birth cohort in India
Authors: Babu Giridhara R. , Murthy G.V.S. , Reddy Yogesh , Deepa R. , Yamuna A. , Prafulla S. , Krishnan Anjaly , Lobo Eunice , Rathnaiah Mohanbabu , Kinra Sanjay 
Published: April 2019

Background: Annually, more than a million Low birthweight (LBW) are born in India, often afflicting disadvantaged families. Several studies have undertaken association of poverty, nutritional status, and obstetric factors with LBW. Through our study, we aimed to examine the possibility of any relation between Edinburgh Postnatal Depression Scale (EPDS) score measured during pregnancy with incidence of babies born Small for Gestational Age (SGA). Moreover, we explored if there is any utility for identifying a cut-off point of EPDS for predicting SGA. Methods: Pregnant women attending the antenatal clinic at a public hospital between 14 to 32 weeks were recruited from April 2016 to Oct 2017. The EPDS was administered to assess depression through face-to-face interviews. Newborn anthropometry was performed post-delivery. For analysis, birth weight <10 percentile was classified as SGA and >90th percentile as Large for Gestational Age (LGA). Results: Prevalence of depressive symptoms (EPDS score >11) was 16.5% (n=108/654) in antenatal mothers. These women delivered a higher proportion of SGA babies (21.3 v/s 15.8) and LGA (9.3 v/s 3.3) compared to women with no symptoms. The odds of women giving birth to a child with SGA were twice as high for women with EPDS scores >11 (adjusted OR = 2.03; 95% CI = 1.12 – 3.70) compared to the women with EPDS scores of ≤11. In terms of Area under curve (AUC), EPDS 11 cut off (AUC: 0.757, CI 0.707- 0.806) was same as EPDS 12 cut-off (AUC: 0.757, CI 0.708- 0.807), which was slightly lower than EPDS 13 cut off (AUC: 0.759 CI 0.709- 0.809). Conclusions: We found a strong association of antenatal depressive symptoms during pregnancy with SGA measured by EPDS. Thus, we recommend implementation of timely and effective screening, diagnostic services, and evidence-based antenatal mental health services in order to combat SGA, and further associated-metabolic syndromes.
Target Cuts from Relaxed Decision Diagrams
Authors: Tjandraatmadja Christian , van Hoeve Willem-Jan 
Published: April 2019

The most common approach to generate cuts in integer programming is to derive them from the linear programming relaxation. We study an alternative approach that extracts cuts from discrete relaxations known as relaxed decision diagrams. Through a connection between decision diagrams and polarity, the algorithm generates cuts that are facet defining for the convex hull of a decision diagram relaxation. As proof of concept, we provide computational evidence that this algorithm generates strong cuts for the maximum independent set problem and the minimum set covering problem. The online appendices are available at https://doi.org/10.1287/ijoc.2018.0830 .
Restoration of anterior teeth using polychromatic layering techniques
Authors: Chandrapal Andrew 
Published: April 2019

The philosophy and procedure of functionally guided anterior restorations is not a new one. The concept does, however, require small points of explanation and detail that the General Dental Practitioner needs to consider in order to secure success in such restorations. This article aims to explore, identify and explain such details with application of a clinical case carried out in general practice. CPD/Clinical Relevance: Functional and aesthetic evaluations required to conduct direct anterior restorations in a logical and predictable method. Employment of systems within a procedure can help to rule out and prevent erroneous errors and inconsistencies that complicate the procedure as well as potentially disappoint the clinician and/or patient.
Minimally Invasive Direct Restoration of Worn Teeth: A Simplified Technique
Authors: Parmar Dipesh 
Published: April 2019

Historically, patients presenting with tooth wear were commonly managed with partial or full coverage cement-retained indirect restorations according to traditional restorative protocols. Conventional rehabilitations are biologically and financially expensive, time consuming and rely heavily on precise laboratory collaboration. Recent advances in adhesive technology and materials have enabled direct composite resin to be used as a minimally invasive alternative in the management of non-carious tooth tissue loss. As extensive direct composite restorations remain technique sensitive and can be time-consuming, this paper describes an innovative, simplified placement technique that uses a progressive diagnostic wax-up, transparent silicone templates and heated composite resin. CPD/Clinical Relevance: The predictable, conservative method of full mouth rehabilitation described in this article is cost-effective and time efficient and can deliver an excellent aesthetic outcome.
Practice in financial support of third party organised conferences and courses at a national level for health care professionals in Europe
Authors: Pašalić Daria , Homšak Evgenija , Buño Antonio , Bergmann Katarzyna , Carru Ciriaco 
Published: April 2019

Abstract

Background
Ethical MedTech prescribes high standards for the participation of the in vitro diagnostics (IVD) industry in third-party organised educational events in terms of charitable donations, educational grants, scholarships and fellowships. We planned a survey to investigate the previous and current practice in terms of cooperation between professionals or professional societies and the IVD industry, as well as plans under the incorporation of the MedTech Europe Code.

Methods
Different questions, from general information to specific questions related to the practice and knowledge of the new Ethical MedTech Code, were included in two different surveys; for European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) National Societies’ (NSs) representatives, and for their (NSs) individual members.

Results
Twenty-five out of 40 EFLM NS representatives replied; more than half declared that all different types of financial resources were available for supporting the continuing professional education of health care professionals (HCPs). In addition, 322 individual responses collected from 31 NSs, answered that the institutional director (50.3%) or laboratory chief (70.1%) made generally made a decision, without specific criteria.

Conclusions
The MedTech Europe Code is already adopted or is about to be adopted in numerous EFLM NSs, but most of them have not implemented it as yet. The use of the Code and better communication between IVD companies and HCPs are necessary to guarantee an improved and fair use of financial support, as well as better choices for the organisation and attendance at scientific events.