bluuebunny/crossref_metadata_2025_split huggingface dataset:
When and why should patients with hematologic malignancies see a palliative care specialist?
Authors: LeBlanc Thomas W. , El-Jawahri Areej 
Published: September 2016

Abstract
Palliative care is a multidisciplinary approach to symptom management, psychosocial support, and assistance in treatment decision-making for patients with serious illness and their families. It emphasizes well-being at any point along the disease trajectory, regardless of prognosis. The term “palliative care” is often incorrectly used as a synonym for end-of-life care, or “hospice care”. However, palliative care does not require a terminal diagnosis or proximity to death, a misconception that we will address in this article. Multiple randomized clinical trials demonstrate the many benefits of early integration of palliative care for patients with cancer, including reductions in symptom burden, improvements in quality-of-life, mood, and overall survival, as well as improved caregiver outcomes. Thus, early concurrent palliative care integrated with cancer-directed care has emerged as a standard-of-care practice for patients with cancer. However, patients with hematologic malignancies rarely utilize palliative care services, despite their many unmet palliative care needs, and are much less likely to use palliative care compared to patients with solid tumors. In this article, we will define “palliative care” and address some common misconceptions regarding its role as part of high-quality care for patients with cancer. We will then review the evidence supporting the integration of palliative care into comprehensive cancer care, discuss perceived barriers to palliative care in hematologic malignancies, and suggest opportunities and triggers for earlier and more frequent palliative care referral in this population.
The antiphospholipid syndrome: still an enigma
Authors: Chaturvedi Shruti , McCrae Keith R. 
Published: September 2016

AbstractAntiphospholipid syndrome (APS) is defined by clinical manifestations that include thrombosis and/or fetal loss or pregnancy morbidity in patients with antiphospholipid antibodies (aPL). Antiphospholipid antibodies are among the most common causes of acquired thrombophilia, but unlike most of the genetic thrombophilias are associated with both venous and arterial thrombosis. Despite an abundance of clinical and basic research on aPL, a unified mechanism that explains their prothrombotic activity has not been defined; this may reflect the heterogeneity of aPL and/or the fact that they may influence multiple pro- and/or antithrombotic pathways. Antiphospholipid antibodies are directed primarily toward phospholipid binding proteins rather than phospholipid per se, with the most common antigenic target being β2-glycoprotein 1 (β2GPI) although antibodies against other targets such as prothrombin are well described. Laboratory diagnosis of aPL depends upon the detection of a lupus anticoagulant (LA), which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin and anti-β2-glycoprotein 1 antibodies. Indefinite anticoagulation remains the mainstay of therapy for thrombotic APS, although new strategies that may improve outcomes are emerging. Preliminary reports suggest caution in the use of direct oral anticoagulants in patients with APS-associated thrombosis. Based on somewhat limited evidence, aspirin and low molecular weight heparin are recommended for obstetrical APS. There remains a pressing need for better understanding of the pathogenesis of APS in humans, for identification of clinical and laboratory parameters that define patients at greatest risk for APS-related events, and for targeted treatment of this common yet enigmatic disorder.
What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura
Authors: Sadler J. Evan 
Published: September 2016

Abstract
Severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency causes thrombotic thrombocytopenic purpura (TTP), which is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and the absence of oliguric or anuric renal failure. However, some patients with this constellation of findings do not have ADAMTS13 deficiency, and some patients with ADAMTS13 deficiency have renal failure or relatively normal blood counts. Consequently, many investigators and clinicians have incorporated severe ADAMTS13 deficiency into the case definition of TTP. This change has facilitated the timely initiation of treatment for patients with atypical clinical features who otherwise would not be recognized as having TTP. Conversely, excluding severe ADAMTS13 deficiency focuses attention on the diagnosis and treatment of other causes of thrombotic microangiopathy that require different treatment. The rapid return of ADAMTS13 data is important to make the best use of this information.
Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange
Authors: Coppo Paul , Froissart Antoine 
Published: September 2016

AbstractDaily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of 80%-85%. However, relapses occur in ∼40% of patients and refractory disease with fatal outcomes still occurs. In this context, the introduction of rituximab has probably been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, or even as frontline therapy, with high response rates. In more severe patients, salvage strategies may include twice-daily TPE, pulses of cyclophosphamide, vincristine, as well as splenectomy in more desperate cases. In this life-threatening disease, relapse prevention represents a major goal. Persistent severe acquired ADAMTS13 deficiency in patients who are otherwise in remission is associated with a high risk of relapse and preemptive treatment with rituximab may be considered in this context. In the coming years, the TTP therapeutic landscape should be enriched by original strategies stemming from clinical experience and new agents that are currently being evaluated in large, ideally international, clinical trials. Promising agents under evaluation include N-acetylcysteine, bortezomib, recombinant ADAMTS13, and inhibitors of the glycoprotein-Ib/IX-von Willebrand factor axis.
Evidence for Janus kinase (JAK) inhibitors for the prevention of major morbid events in patients with myeloproliferative neoplasms (MPNs)
Authors: Pemmaraju Naveen , Mesa Ruben 
Published: September 2016

Abstract
A 69-year-old man presents with a Dynamic International Prognostic Scoring System (DIPSS) intermediate-risk 2 post polycythemia vera myelofibrosis with significant splenomegaly, 30 pound weight loss, constitutional symptoms, and 2% peripheral blood blasts. He has no other significant past medical history and no other major comorbid conditions. You are asked by the hematology fellow you are supervising whether or not treating this patient with a Janus kinase (JAK) inhibitor will decrease major morbid events.
B-cell receptor pathway modulators in NHL
Authors: Blum Kristie A. 
Published: September 2016

AbstractWith the recent success of the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, and the phosphoinositide-3-kinase (PI3K) inhibitor, idelalisib, in the treatment of patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), a number of new agents targeting the B-cell receptor (BCR) pathway are in clinical development. In addition, multiple trials combining these agents with conventional cytotoxic chemotherapy, immunomodulatory agents, monoclonal antibodies, or other kinase inhibitors are underway. This review will summarize the current data with the use of single agent and combination therapy with BCR inhibitors in NHL. In addition, commonly encountered as well as serious toxicities and hypothesized resistance mechanisms will be discussed. Lastly, this review will examine the future of these agents and opportunities to maneuver them into the front-line setting in selected NHL subtypes.
Diagnosis and management of mastocytosis: an emerging challenge in applied hematology
Authors: Valent Peter 
Published: September 2016

Abstract
Mastocytosis is a unique and rare neoplasm defined by abnormal expansion and accumulation of clonal mast cells (MCs) in one or multiple organ systems. Most adult patients are diagnosed to have systemic mastocytosis (SM). Based on histological findings and disease-related organ damage, SM is classified into indolent SM (ISM), smoldering SM (SSM), SM with an associated hematologic non-MC-lineage disease (SM-AHNMD), aggressive SM (ASM), and MC leukemia (MCL). The clinical picture, course, and prognosis vary profoundly among these patients. Nonetheless, independent of the category of SM, neoplastic cells usually exhibit the KIT point-mutation D816V. However, in advanced SM, additional molecular defects are often detected and are considered to contribute to disease progression and drug resistance. These lesions include, among others, somatic mutations in TET2, SRSF2, ASXL1, CBL, RUNX1, and RAS. In SM-AHNMD, such mutations are often found in the “AHNMD component” of the disease. Clinical symptoms in mastocytosis result from (1) the release of proinflammatory and vasoactive mediators from MCs, and (2) SM-induced organ damage. Therapy of SM has to be adjusted to the individual patient and the SM category: in those with ISM and SSM, the goal is to control mediator secretion and/or mediator effects, to keep concomitant allergies under control, and to counteract osteoporosis, whereas in advanced SM (ASM, MCL, and SM-AHNMD) anti-neoplastic drugs are prescribed to suppress MC expansion and/or to keep AHNMD cells under control. Novel drugs directed against mutated KIT and/or other oncogenic kinase targets are tested currently in these patients. In rapidly progressing and drug-resistant cases, high-dose polychemotherapy and stem cell transplantation have to be considered.
Pathogen metadata platform: software for accessing and analyzing pathogen strain information
Authors: Chang Wenling E. , Peterson Matthew W. , Garay Christopher D. , Korves Tonia 
Published: September 2016

Abstract
Background
Pathogen metadata includes information about where and when a pathogen was collected and the type of environment it came from. Along with genomic nucleotide sequence data, this metadata is growing rapidly and becoming a valuable resource not only for research but for biosurveillance and public health. However, current freely available tools for analyzing this data are geared towards bioinformaticians and/or do not provide summaries and visualizations needed to readily interpret results.

Results
We designed a platform to easily access and summarize data about pathogen samples. The software includes a PostgreSQL database that captures metadata useful for disease outbreak investigations, and scripts for downloading and parsing data from NCBI BioSample and BioProject into the database. The software provides a user interface to query metadata and obtain standardized results in an exportable, tab-delimited format. To visually summarize results, the user interface provides a 2D histogram for user-selected metadata types and mapping of geolocated entries. The software is built on the LabKey data platform, an open-source data management platform, which enables developers to add functionalities. We demonstrate the use of the software in querying for a pathogen serovar and for genome sequence identifiers.

Conclusions
This software enables users to create a local database for pathogen metadata, populate it with data from NCBI, easily query the data, and obtain visual summaries. Some of the components, such as the database, are modular and can be incorporated into other data platforms. The source code is freely available for download at https://github.com/wchangmitre/bioattribution.
Protective effect of melatonin on soluble Aβ1–42-induced memory impairment, astrogliosis, and synaptic dysfunction via the Musashi1/Notch1/Hes1 signaling pathway in the rat hippocampus
Authors: Zhang Shuman , Wang Pan , Ren Lili , Hu Chunli , Bi Jing 
Published: September 2016

Abstract
Background
Amyloid-beta (Aβ) plays a key role in Alzheimer’s disease (AD) pathogenesis, and soluble Aβ oligomers are more cytotoxic than Aβ fibrils. Recent evidence suggests that Notch signaling is affected by AD and other brain diseases. Melatonin exerts beneficial effects on many aspects of AD and may protect against myocardial ischemia via Notch1 signaling regulation. Therefore, we hypothesized that the Notch1 signaling pathway is involved in the neuroprotective role of melatonin against soluble Aβ1–42.

Methods
An AD rat model was established via repeated intracerebroventricular administration of soluble Aβ1–42. Melatonin treatment was administered 24 hours prior to Aβ1–42 administration via an intraperitoneal injection. The effects of melatonin on spatial learning and memory, synaptic plasticity, and astrogliosis were investigated. The expression of several Notch1 signaling components, including Notch1, the Notch1 intracellular domain (NICD), Hairy and enhancer of split 1 (Hes1, a downstream effector of Notch), and Musashi1 (a positive regulator of Notch), were examined using immunohistochemistry, western blotting, and quantitative real-time PCR. In vitro studies were conducted to determine whether the melatonin-mediated protection against Aβ1–42 was inhibited by DAPT, an inhibitor of Notch signaling.

Results
Melatonin improved the Aβ1–42-induced impairment in spatial learning and memory, attenuated synaptic dysfunction, and reduced astrogliosis. Melatonin also ameliorated the effects of Aβ1–42 on Notch1, NICD, Hes1, and Musashi1. The in vitro studies demonstrated that DAPT effectively blocked the neuroprotective effect of melatonin against Aβ1–42.

Conclusions
These findings suggest that melatonin may improve the soluble Aβ1–42-induced impairment of spatial learning and memory, synaptic plasticity, and astrogliosis via the Musashi1/Notch1/Hes1 signaling pathway.
Bithiophene with Winding Vine-shaped Molecular Asymmetry. Preparation, Structural Characterization, and Enantioselective Synthesis
Authors: Toyomori Yuka , Tsuji Satoru , Mitsuda Shinobu , Okayama Yoichi , Ashida Shiomi , Mori Atsunori , Kobayashi Toru , Miyazaki Yuji , Yaita Tsuyoshi , Arae Sachie , Takahashi Tamotsu , Ogasawara Masamichi 
Published: September 2016

Abstract
Preparation of 2,2′-bithiophene derivatives bearing ω-alkenyl groups at the 3,3′-positions and ring-closing metathesis reactions of the obtained compound were performed. The reaction of bithiophene bearing 3-butenyl substituents 1 with 5 mol % Grubbs 1st generation catalyst underwent ring-closing metathesis (RCM) to afford the cyclized product 7 showing winding vine-shaped molecular asymmetry in up to 88% yield. Enantioselective RCM was also achieved by the use of chiral Schrock–Hoveyda molybdenum-alkylidene catalyst in up to 87% ee.
Smartglasses for the Triage of Casualties and the Identification of Hazardous Materials
Authors: Berndt Henrik , Mentler Tilo , Herczeg Michael 
Published: September 2016

Abstract
Emergency Medical Services (EMS) can be confronted with complex and challenging situations with many casualties that require special procedures and organizational structures. In order to keep control and records, incident commanders use paper-based notes, lists and forms. The increasing availability of smartglasses leads to the research question, whether they can support members of EMS and improve processes and efficiency. In this contribution, we describe use cases for smartglasses in emergency medicine, such as the triage in incidents with many casualties and the recognition of hazardous materials in accident contexts. We describe results from interviews with 10 members of EMS and civil protection units in Germany and from prototypical applications that have been developed and evaluated together with domain experts. The prototypical applications described in this contribution have shown promising results with respect to usability and acceptance.
Head-Mounted Displays in German Companies A Virtual, Augmented and Mixed Reality Check
Authors: Esser Ralf , Oppermann Leif 
Published: September 2016

Abstract
In 2020, German companies will spend close to €850 million on Virtual and Mixed Reality hardware and solutions based on smart glasses. The lion’s share will be spent on innovative applications.
This text provides some guidance in this rising market by categorizing the available smart glasses and head-mounted displays into five categories and the potential business application fields into a further eight categories. Finally, it presents a matrix of suitable devices per application field.
Introduction to this Special Issue on Smart Glasses
Authors: Oppermann Leif , Prinz Wolfgang 
Published: September 2016

Abstract
The idea of augmented or virtual reality in combination with head mounted display is being discussed already since at least 1968. However, for a long time, this topic was discussed mainly within the academic research area with only limited effect or uptake in the work place. Primary reason for this was the missing availability of robust and affordable hardware as well as the limited mobile graphics capabilities. This has changed recently with the availability of numerous affordable devices in combination with applications from the entertainment and gaming area.
This Special Issue on Smart Glasses presents a mix of recent research papers and reports to provide an overview of ongoing research and developments in work place environments. In the remainder of this introductory paper we present an overview of the history of Smart Glasses and their applications over the last decades. We also clarify the term Augmented Reality in this historic context. Then we present a topology of current products as well as their intended application areas. Finally, we introduce the papers of this issue within this context.
Dark silicon management: an integrated and coordinated cross-layer approach
Authors: Pagani Santiago , Bauer Lars , Chen Qingqing , Glocker Elisabeth , Hannig Frank , Herkersdorf Andreas , Khdr Heba , Pathania Anuj , Schlichtmann Ulf , Schmitt-Landsiedel Doris , Sagi Mark , Sousa Éricles , Wagner Philipp , Wenzel Volker , Wild Thomas , Henkel Jörg 
Published: September 2016

Abstract
This paper presents an integrated and coordinated cross-layer sensing and optimization flow for distributed dark silicon
management for tiled heterogeneous manycores under a critical temperature constraint. We target some of the key challenges
in dark silicon for manycores, such as: directly focusing on power density/temperature instead of considering simple
per-chip power constraints, considering tiled heterogeneous architectures with different types of cores and accelerators,
handling the large volumes of raw sensor information, and maintaining scalability. Our solution is separated into three
abstraction layers: a sensing layer (involving hardware monitors and pre-processing), a dark silicon layer (that derives
thermally-safe mappings and voltage/frequency settings), and an agent layer (used for selecting the parallelism of
applications and thread-to-core mapping based on alternatives/constraints from the dark silicon layer).
Single Machine Scheduling Based on EDD-SDST-ACO Heuristic Algorithm
Authors: Song Haicao , Yi Shuping , Liu Mi , Qin Gaoyang 
Published: September 2016

Abstract
A large number of changeovers exist in multi-item and small lot size production mode, which lead to a long setup time and significantly influence productivity. However, setup time has received significantly less attention in previous studies regarding the single machine scheduling (SMS) problem. This paper investigates the SMS problem with sequence-dependent setup time (SDST). First, a model of SMS-SDST is developed to minimise the makespan. An earliest due date (EDD), SDST, and ant colony optimisation (ACO) heuristic algorithm is presented. In order to evaluate the performance of the proposed algorithm, Taguchi’s robust design method is employed to define the best parameter values. Related results are analysed by statistical tools. The computational experiments are compared with an ACO algorithm and a genetic algorithm. The experimental results and statistical analyses show that the proposed EDD-SDST-ACO is effective for the problem.
Chemosensitivity and resistance testing in malignant effusions with focus on primary malignant mesothelioma and metastatic adenocarcinoma
Authors: Szulkin Adam , Szatmári Tünde , Hjerpe Anders , Dobra Katalin 
Published: September 2016

AbstractCell based chemosensitivity and resistance testing is an attractive approach that offers functional measurement of drug responseex vivowith the ultimate goal to guide the choice of chemotherapy for various cancers. Thus, it has a great potential to select patients for the optimal treatment option, thereby offering a tool for personalized cancer therapy.Despite several decades of intensive scientific effortsex-vivotests are still not incorporated in the standard of care. Limited access to fresh tumor tissue, unsatisfactory models and single readout as endpoint constitute major hindrance. Thus, establishing and validating clinically useful and reliable model systems still remains a major challenge.Here we present malignant effusions as valuable sources forex-vivochemosensitivity and resistance testing. Accumulation of a malignant effusion in the pleura, peritoneum or pericardium is often the first diagnostic material for both primary malignant mesothelioma and a broad spectrum of metastatic adenocarcinoma originating from lung-, breast-, ovary- and gastro-intestinal organs as well as lymphoma.In contrast to biopsies, in these effusions malignant cells are easily accessible and often abundant. Effusion derived cells can occur dissociated or forming three-dimensional papillary structures that authentically recapitulate the biology of the corresponding tumor tissue and offer models forex vivotesting. In addition, effusions have the advantage of being available prior to or concurrent with the pathological review, thus constituting an excellent source of viable cells for simultaneous molecular profiling, biomarker analysis and for establishing primary cells for studying tumor biology and resistance mechanisms.For a reliable test, however, a careful validation is needed, taking into account the inherited heterogeneity of malignant tumors, but also the complex interplay between malignant and benign cells, which are always present in this setting.