bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and laboratory diagnosis of TTP: an integrated approach
Authors: Chiasakul Thita , Cuker Adam 
Published: April 2019

Abstract
Thrombotic thrombocytopenia purpura (TTP) is a rare, life-threatening disease with an incidence of approximately 2 persons per million per year. It is characterized by severe deficiency of the von Willebrand cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), leading to formation of platelet-rich thrombi in the microvasculature. Prompt initiation of appropriate therapy, particularly plasma exchange, may be life-saving. Diagnosis of TTP is challenging because of its diverse clinical manifestations, overlap in clinical presentation with other thrombotic microangiopathies, and limited availability of ADAMTS13 testing. Clinical prediction scores have been developed to estimate the pretest probability of severe ADAMTS13 deficiency and may be used as an adjunct to clinical judgment to guide initial management decisions. An ADAMTS13 activity level of less than 10% supports the diagnosis of TTP in appropriate clinical contexts, but many centers do not offer testing in-house and must send out the test to a reference laboratory with a turnaround time of several days. In such instances, initial management decisions must be made without the benefit of laboratory testing. In patients with TTP, inhibitor tests may be useful for distinguishing immune-mediated from congenital TTP. In this article, we review the epidemiology, natural history, and clinical presentation of TTP and laboratory assays for TTP including ADAMTS13 activity and inhibitor assays. We also describe an evidence-based approach to the evaluation of a patient with suspected TTP that integrates clinical and laboratory assessment.
Genomics of aggressive B-cell lymphoma
Authors: Rosenthal Allison , Rimsza Lisa 
Published: April 2019

Abstract
The growing body of genomic information collected and applied to mature aggressive B-cell lymphoma diagnosis and management has exploded over the last few years due to improved technologies with high-throughput capacity, suitable for use on routine formalin-fixed, paraffin-embedded tissue biopsies, and decreasing costs. These techniques have made evaluation of complete DNA sequences, RNA-expression patterns, translocations, copy-number alterations, loss of heterozygosity, and DNA-methylation patterns possible on a genome-wide level. This chapter will present a case of aggressive B-cell lymphoma and discuss the most important genomic abnormalities that characterize this group of entities in the recent update to the fourth edition of the World Health Organization (WHO) lymphoma classification system. Genomic abnormalities discussed will include those necessary for certain diagnoses such as translocations of MYC, BCL2, or BCL6; gene-expression-profiling categorization; the newly defined Burkitt-like lymphoma with 11q abnormalities; prognostic and predictive mutations, as well as tumor heterogeneity. Finally, our current practices for clinical triage of specimens with a potential diagnosis of aggressive B-cell lymphomas are also described. Options for treatment at relapse, in light of these genomic features, will be discussed in the third presentation from this session.
Novel therapies for relapsed/refractory aggressive lymphomas
Authors: Cohen Jonathon B. 
Published: April 2019

AbstractMost patients with aggressive non-Hodgkin lymphoma will be cured with initial chemoimmunotherapy; however, most patients with relapsed disease will not be cured and will die as a result of their disease. In these cases, continued treatment with conventional chemotherapy is typically not of benefit and can contribute to significant toxicities and decreased quality of life for patients. Fortunately, a number of therapies are currently available or under investigation for this group of patients, ranging from oral tyrosine kinase inhibitors targeting multiple pathways within the malignant cells to adoptive cellular therapies that harness the patient’s immune system to fight disease. Additionally, many agents that are modestly effective as monotherapies can be safely combined with additional novel and conventional therapies to improve response rates and duration. Chimeric antigen receptor T cells are among the most promising group of therapies and provide the potential for cure for patients with relapsed/refractory lymphoma. In this chapter, we will review the currently available novel treatments as well as those still under investigation and discuss the most appropriate approach to patients with relapsed/refractory aggressive lymphoma. We will highlight the challenges associated with these therapies, as well as potential toxicities, and the need for additional clinical trials evaluating combinations and newer treatments.
Antibody-based therapies in patients with acute lymphoblastic leukemia
Authors: Dinner Shira , Liedtke Michaela 
Published: April 2019

AbstractThe use of multiagent combination chemotherapy regimens results in cure rates of >90% for children and ∼40% for adults with acute lymphoblastic leukemia (ALL) but is associated with extensive toxicity and disappointingly low efficacy in relapsed patients. ALL blast cells express several surface antigens, including CD20, CD22, and CD19, which represent valuable targets for immunotherapy. Monoclonal antibodies, antibody–drug conjugates, and bispecific T-cell–engaging antibodies targeting these antigens offer novel mechanisms of action. Within the last several years, the anti-CD20 antibody rituximab has been added to chemotherapy for newly diagnosed patients <60 years with CD20+ pre-B ALL and significantly improved the 2-year event-free survival from 52% to 65%. In adults with relapsed or refractory CD22+ ALL, the antibody–drug conjugate inotuzumab ozogamicin resulted in a complete response rate of 81% and median overall survival of 7.7 months with reduced toxicity compared with standard chemotherapy. Similarly, the bispecific T-cell–engaging antibody blinatumomab yielded a complete response rate of 44% and a median overall survival of 7.7 months in an extensively treated ALL population. Moreover, ∼80% of ALL patients in complete remission with evidence of minimal residual disease (MRD) achieved a complete MRD response following treatment with blinatumomab. These results highlight the tremendous promise of antibody-based treatment approaches for ALL. Ongoing and future research is critical to further define the role of the various immunotherapies in the frontline treatment of ALL. Additional challenges include the optimal sequencing of the available antibodies in the relapsed setting as well as their integration with stem cell transplant and chimeric antigen receptor T-cell therapy.
Effects of Metreleptin on Proteinuria in Patients With Lipodystrophy
Authors: Lee Ho Lim , Waldman Meryl A , Auh Sungyoung , Balow James E , Cochran Elaine K , Gorden Phillip , Brown Rebecca J 
Published: April 2019

Abstract

Context
Patients with lipodystrophy have high prevalence of proteinuria.

Objective
To assess kidney disease in patients with generalized (GLD) vs partial lipodystrophy (PLD), and the effects of metreleptin on proteinuria in patients with lipodystrophy.

Design, Setting, Patients, Intervention
Prospective, open-label studies of metreleptin treatment in patients with GLD and PLD at the National Institutes of Health.

Outcome Measures
The 24-hour urinary albumin and protein excretion rates, estimated glomerular filtration rate (eGFR), and creatinine clearance (CrCl) were measured at baseline and during up to 24 months of metreleptin treatment. Patients with increases in medications affecting outcome measures were excluded.

Results
At baseline, patients with GLD had significantly greater albuminuria, proteinuria, eGFR, and CrCl compared with patients with PLD. CrCl was above the normal range in 69% of patients with GLD and 39% with PLD (P = 0.02). With up to 24 months of metreleptin treatment, there were significant reductions in albuminuria and proteinuria in patients with GLD, but not in those with PLD. No changes in eGFR or CrCl were observed in patients with GLD or PLD during metreleptin treatment.

Conclusions
Patients with GLD had significantly greater proteinuria than those with PLD, which improved with metreleptin treatment. The mechanisms leading to proteinuria in lipodystrophy and improvements in proteinuria with metreleptin are not clear. Hyperfiltration was also more common in GLD vs PLD but did not change with metreleptin.
Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium
Authors: Bazzoun D. , Adissu H. A. , Wang L. , Urazaev A. , Tenvooren I. , Fostok S. F. , Chittiboyina S. , Sturgis J. , Hodges K. , Chandramouly G. , Vidi P.-A. , Talhouk R. S. , Lelièvre S. A. 
Published: April 2019

ABSTRACT
Cell–cell communication is essential for tissue homeostasis, but its contribution to disease prevention remains to be understood. We demonstrate the involvement of connexin 43 (Cx43, also known as GJA1) and related gap junction in epithelial homeostasis, illustrated by polarity-mediated cell cycle entry and mitotic spindle orientation (MSO). Cx43 localization is restricted to the apicolateral membrane of phenotypically normal breast luminal epithelial cells in 3D culture and in vivo. Chemically induced blockade of gap junction intercellular communication (GJIC), as well as the absence of Cx43, disrupt the apicolateral distribution of polarity determinant tight junction marker ZO-1 (also known as TJP1) and lead to random MSO and cell multilayering. Induced expression of Cx43 in cells that normally lack this protein reestablishes polarity and proper MSO in 3D culture. Cx43-directed MSO implicates PI3K–aPKC signaling, and Cx43 co-precipitates with signaling node proteins β-catenin (CTNNB1) and ZO-2 (also known as TJP2) in the polarized epithelium. The distribution of Cx43 is altered by pro-inflammatory breast cancer risk factors such as leptin and high-fat diet, as shown in cell culture and on tissue biopsy sections. The control of polarity-mediated quiescence and MSO may contribute to the tumor-suppressive role of Cx43.
Homeostasis of soluble proteins and the proteasome post nuclear envelope reformation in mitosis
Authors: Spits Menno , Janssen Lennert J. , Voortman Lenard M. , Kooij Raymond , Neefjes Anna C. M. , Ovaa Huib , Neefjes Jacques 
Published: April 2019

ABSTRACT
Upon nuclear envelope (NE) fragmentation in the prometaphase, the nuclear and cytosolic proteomes mix and must be redefined to reinstate homeostasis. Here, by using a molecular GFP ladder, we show that in early mitosis, condensed chromatin excludes cytosolic proteins. When the NE reforms tightly around condensed chromatin in late mitosis, large GFP multimers are automatically excluded from the nucleus. This can be circumvented by limiting DNA condensation with Q15, a condensin II inhibitor. Soluble small and other nuclear localization sequence (NLS)-targeted proteins then swiftly enter the expanding nuclear space. We then examined proteasomes, which are located in the cytoplasm and nucleus. A significant fraction of 20S proteasomes is imported by the importin IPO5 within 20 min of reformation of the nucleus, after which import comes to an abrupt halt. This suggests that maintaining the nuclear–cytosol distribution after mitosis requires chromatin condensation to exclude cytosolic material from the nuclear space, and specialized machineries for nuclear import of large protein complexes, such as the proteasome.
Form ever follows function: the occlusal compass and direct resin composite restorations
Authors: Smithson Jason 
Published: April 2019

Direct composite resins in the posterior dentition are a day-to-day treatment modality for most dental practitioners. It is challenging for many operators to produce a restoration that is both aesthetic and functional in a clinically realistic timeframe. This article helps to address this. CPD/Clinical Relevance: To present a functionally-generated approach to occlusal anatomy based on the DeVreugd Occlusal Compass to simplify the placement of direct composite resin in the Class I and II situation.
How Visible Light Curing came into Dentistry
Authors: Wilson Nairn HF 
Published: April 2019

This paper details the history of the introduction of visible light curing into dentistry. This history provides an excellent example of ‘out of the box’ lateral thinking translation of innovative scientific technology into dentistry. Visible light curing is an important UK contribution to the recent history and current practice of dentistry, with several million visible light curing procedures being carried out globally on a daily basis. CPD/Clinical Relevance: Given the importance of visible light curing in dentistry, its history is of relevance.
Fibre-Reinforced Composite Splint – Step-by-Step Instructions
Authors: van Rensburg Jansen 
Published: April 2019

Tooth mobility is commonly seen in general dental practice, usually resulting from chronic periodontitis. A fibre-reinforced composite splint may be used to treat mobile teeth successfully. This article will concentrate on the precise steps on how to place such a periodontal splint. Minimally invasive options should always be considered. In long-term maintenance of periodontally involved teeth where the active disease is under control, the periodontal splint can be very helpful as part of a comprehensive periodontal treatment plan. CPD/Clinical Relevance: A fibre-reinforced composite periodontal splint may improve the masticatory ability and consequently the patient's quality of life.
The E-Cohomological Conley Index, Cup-Lengths and the Arnold Conjecture on T
2n
Authors: Starostka Maciej , Waterstraat Nils 
Published: April 2019

Abstract
We show that the E-cohomological Conley index, that was introduced by the first author recently, has a natural module structure. This yields a new cup-length and a lower bound for the number of critical points of functionals on Hilbert spaces. When applied to the setting of the Arnold conjecture, this paves the way to a short proof on tori, where it was first shown by C. Conley and E. Zehnder in 1983.
Comparison of six commercial serum exosome isolation methods suitable for clinical laboratories. Effect in cytokine analysis
Authors: Macías Mónica , Rebmann Vera , Mateos Beatriz , Varo Nerea , Perez-Gracia Jose Luis , Alegre Estibaliz , González Álvaro 
Published: April 2019

Abstract

Background
Exosomes are nanovesicles released by cells that can be detected in blood. Exosomes contain several molecules, such as cytokines that have potential utility as disease biomarkers. The aim of the present work is to compare six different commercial kits suitable for the clinical laboratory in relation to the efficiency and purity of exosome isolation, and their effect in subsequent cytokines analysis.

Methods
Serum exosomes were obtained from 10 volunteers using six commercial kits: exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus and Exo-Flow. Exosome concentrations and size distributions were quantified by nanoparticle tracking analysis. Exosome markers CD63, CD9 and TSG101 were determined by Western blot. ApoB and albumin were measured using nephelometry. S100A9, CXCL5 and CXCL12 were measured using a Luminex assay.

Results
The concentration of particles obtained between different kits varied by a factor of 100. There was no correlation in particle concentrations extracted between different kits, except between ExoQuick and Exo-Flow. The highest exosome purity was achieved with ExoQuick Plus and exoEasy, while the lowest were achieved with ME and ExoQuick. Albumin was present in all exosome extracts analyzed and ApoB in all except those extracted with Exo-Flow and ME. Cytokine detection varied depending on the purification kit used and there was no correlation in cytokine concentrations between samples obtained with different kits.

Conclusions
Both the sample and the type of commercial kit used affect the efficiency and purity of exosome isolation. In addition, the exosome purification method deeply affects the capability to detect and quantify cytokines.
Hypothetical Accident in Polish Nuclear Power Plant. Worst Case Scenario for Main Polish Cities
Authors: Mazur Andrzej 
Published: April 2019

Abstract
Poland is under threat of potential accidents in nuclear power plants located in its close vicinity, in almost all neighboring countries. Moreover, there are plans to establish a new nuclear power plant in Polish coast. In this paper the analysis of atmospheric transport of radioactive material released during a potential accident in the future nuclear power plant is presented. In the first part of study transport of radioactivity as seen from the long time perspective is analyzed. This involves trajectory analysis as a tool for describing the statistics of air pollution transport pattern and screening the meteorological situations for episode studies. Large sets of meteorological data for selected episodes were stored as a result of this process. Estimation of risk includes both analysis of the consequences and probability analysis of an occurrence of such situation. Episodes then were comprehensively studied in the second phase of the study, using the Eulerian dispersion model for simulation of atmospheric transport of pollutants. This study has proven that the time needed for reaction in case of (hypothetical) accident is enormously short.
Reconstruction of Dynamics of SO2 Concentration in Troposphere Based on Results of Direct Measurements
Authors: Gac Jakub M. , Petelczyc Monika 
Published: April 2019

Abstract
A method for the reconstruction of the dynamics of processes with discrete time, developed in our previous papers, has been applied for study the dynamics of concentration of sulfur dioxide in lower troposphere. For the analysis, recordings of sulfur dioxide concentration from four measurement stations located in Poland (two of them has been located in huge cities and two in rarely inhabited regions) were used. We managed to obtain the deterministic and stochastic component of this dynamics. In result, we estimate the lifetime of sulfur dioxide in troposphere and the increase of sulfur dioxide concentration influenced by anthropogenic sources.
Hydrochemical Diversity of a Large Alluvial Aquifer in an Arid Zone (Draa River, S Morocco)
Authors: Szczucińska Anna , Dłużewski Maciej , Kozłowski Rafał , Niedzielski Przemysław 
Published: April 2019

Abstract
In arid areas, with rivers functioning episodically, alluvial resources are the main source of water. Considering the intensified regulation of discharge in montane catchments, supplying the intermittent rivers, in the nearest future alluvial aquifers will gain key importance for the functioning of people in arid zones. The research aimed to investigate the diversified chemistry of alluvial waters typical of large intermittent river valleys in hot arid zones as well as to analyse processes determining the water chemistry and affecting its diversity. The detailed study, carried out in October 2015, covered the Draa river valley (1100 km total length) in the region of the Mhamid Oasis. The examined water was sampled from all wells found in the study area. Concentrations of the main cations: Ca2+, Mg2+, K+, Na+, NH4
+, and Li+, anions: Cl−, SO4
2−, HCO3
−, and NO3
−, as well as trace elements: Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, and Zn, were identified. Results were analysed with statistical, hydrochemical, and geochemical modelling methods. Alluvial waters of the eastern and western part of the oasis differed in concentrations of numerous components, what resulted from the regulation of irrigation. Specific electrical conductivity showed a 3.5-fold increase, from 3800 to 13800 μS/cm, consistent with the direction of water flow in the oasis, from east to west. Even a greater rise was observed for ions: Cl− (6x), Na+ (5.5x), Mg2+ (5.0x), Ca2+, and SO4
2− (3.5x). Such a composition indicated multiionic hydrochemical type of waters dominated by Na+ and Cl−. Additionally, high Pearson correlation coefficients were recorded for Na+ and Cl− (0.98) as well as Mg2+ and Cl− (0.97). The saturation index suggested that the main water components originated from dissolving of minerals such as halite, anhydrite, sylvite, and gypsum. Groundwater chemistry in the Mhamid Oasis was determined mainly by geogenic processes, such as dissolving of evaporates, precipitation of carbonate minerals, and ion exchange.
Geostatistical Methods in Water Distribution Network Design - A Case Study
Authors: Potyralla Maciej 
Published: April 2019

AbstractModeling of the loads of water supply networks and their subsequent forecasting is an element necessary for making optimum decisions in the process of planning the development and operation of the water supply networks. The results of this modeling are decisive for the selection of the diameters of the pipelines and their arrangement on the water demand area. This study presents the results of estimation of average values of loads for the selected investment variants. The aim of the article is to present the possibility of simulations and analyses of the geostatistical interpolation methods. Data input in the model regarded the fragment of the real water supply network administered by the Municipal Water and Sewerage Company in Warszawa. Results of the computer analyses for the presented investment variants were related to the operating data of the water supply network and the data on water demand for the years 2014-2017 and 2018-2025. The aim of this paper is to present the advantages of GIS for the water supply systems and to prove that using the appropriate IT system, with provision of proper data processing, may lead to decisions which are optimum in view of the established, often very complex criteria.
The Effect of Different Forms of Sulphur on Incidence of Apple Scab on Apple Tree (Malus x domestica Borkh) Gloster CV.
Authors: Bělíková Hana , Mészáros Martin , Varga Ladislav , Árvay Július , Wiśniowska-Kielian Barbara , Gondek Krzysztof , Antonkiewicz Jacek , Torma Stanislav , Lazarević Boris , Von Bennewitz Eduardo , Lošák Tomáš 
Published: April 2019

Abstract
From 2014 to 2015 the influence of foliar application of sulphur on apple trees (Gloster cv.)was investigated in the apple orchard at the Research and Breeding Institute of Pomology in Holovousy (North-East Bohemia, Czech Republic). The experiment was based on foliar applications of fertilizers containing different forms of sulphur: elemental S0, sulphate SO4
2− and thiosulphate S2O3
2− (in combination with other macro- and microelements) and fungicides with or without sulphur: Kumulus (S0 + F) and the conventional fungicide programme (F), in the respective treatments. Apple scab incidence on leaves and fruits was investigated in each experimental year according to the relevant methodology of the OEPP/EPPO standard PP1/5(3) Venturia inaequalis. Data on the incidence of apple scab correlate with the process of pathogen life cycle and risk of infection on the given dates. The incidence of apple scab was the lowest in 2014 in treatment S0 + F (10.8 % on leaves, 2.8 % on fruits) and F (15.8 % on leaves, 6 % on fruits) where conventional fungicides were used. When compared with the other treatments these treatments were the most effective even if the incidence of scab in the individual treatments in 2015 increased by 28 to 60 % due to high infection pressure. The results confirmed the efficiency of the conventional fungicide programme (S0 + F and F) against apple scab incidence on fruits. What is more, the results were slightly better in the treatment, where the conventional fungicide programme was combined with fertilizer containing elemental S (S0 + F) in comparison with fungicides applied alone (F). The effect of the other forms of sulphur (SO4 and S2O3) on apple scab control has not been confirmed. According to the results, the application of the conventional fungicide programme (S0 + F and F) is more effective against scab incidence than the inorganic forms of sulphur alone.