bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis
Authors: Folkerts Hendrik , Wierenga Albertus T. , van den Heuvel Fiona A. , Woldhuis Roy R. , Kluit Darlyne S. , Jaques Jennifer , Schuringa Jan Jacob , Vellenga Edo 
Published: May 2019

AbstractVacuole membrane protein (VMP1) is a putative autophagy protein, which together with Beclin-1 acts as a molecular switch in activating autophagy. In the present study the role of VMP1 was analysed in CD34+ cells of cord blood (CB) and primary acute myeloid leukemia (AML) cells and cell lines. An increased expression of VMP1 was observed in a subset of AML patients. Functional studies in normal CB CD34+ cells indicated that inhibiting VMP1 expression reduced autophagic-flux, coinciding with reduced expansion of hematopoietic stem and progenitor cells (HSPC), delayed differentiation, increased apoptosis and impaired in vivo engraftment. Comparable results were observed in leukemic cell lines and primary AML CD34+ cells. Ultrastructural analysis indicated that leukemic cells overexpressing VMP1 displayed a reduced number of mitochondrial structures, while the number of lysosomal degradation structures was increased. The overexpression of VMP1 did not affect cell proliferation and differentiation, but increased autophagic-flux and improved mitochondrial quality, which coincided with an increased threshold for venetoclax-induced loss of mitochondrial outer membrane permeabilization (MOMP) and apoptosis. In conclusion, our data indicate that in leukemic cells high VMP1 is involved with mitochondrial quality control.
Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
Authors: Lloyd-Price Jason , Arze Cesar , Ananthakrishnan Ashwin N. , Schirmer Melanie , Avila-Pacheco Julian , Poon Tiffany W. , Andrews Elizabeth , Ajami Nadim J. , Bonham Kevin S. , Brislawn Colin J. , Casero David , Courtney Holly , Gonzalez Antonio , Graeber Thomas G. , Hall A. Brantley , Lake Kathleen , Landers Carol J. , Mallick Himel , Plichta Damian R. , Prasad Mahadev , Rahnavard Gholamali , Sauk Jenny , Shungin Dmitry , Vázquez-Baeza Yoshiki , White Richard A. ,   IBDMDB Investigators, Bishai Jason , Bullock Kevin , Deik Amy , Dennis Courtney , Kaplan Jess L. , Khalili Hamed , McIver Lauren J. , Moran Christopher J. , Nguyen Long , Pierce Kerry A. , Schwager Randall , Sirota-Madi Alexandra , Stevens Betsy W. , Tan William , ten Hoeve Johanna J. , Weingart George , Wilson Robin G. , Yajnik Vijay , Braun Jonathan , Denson Lee A. , Jansson Janet K. , Knight Rob , Kugathasan Subra , McGovern Dermot P. B. , Petrosino Joseph F. , Stappenbeck Thaddeus S. , Winter Harland S. , Clish Clary B. , Franzosa Eric A. , Vlamakis Hera , Xavier Ramnik J. , Huttenhower Curtis 
Published: May 2019

AbstractInflammatory bowel diseases, which include Crohn’s disease and ulcerative colitis, affect several million individuals worldwide. Crohn’s disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study’s infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi’omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.
The Integrative Human Microbiome Project
Authors:   The Integrative HMP (iHMP) Research Network Consortium, Proctor Lita M. , Creasy Heather H. , Fettweis Jennifer M. , Lloyd-Price Jason , Mahurkar Anup , Zhou Wenyu , Buck Gregory A. , Snyder Michael P. , Strauss Jerome F. , Weinstock George M. , White Owen , Huttenhower Curtis 
Published: May 2019

AbstractThe NIH Human Microbiome Project (HMP) has been carried out over ten years and two phases to provide resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The recently completed second phase, the Integrative Human Microbiome Project, comprised studies of dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth; inflammatory bowel diseases; and stressors that affect individuals with prediabetes. The associated research begins to elucidate mechanisms of host–microbiome interactions under these conditions, provides unique data resources (at the HMP Data Coordination Center), and represents a paradigm for future multi-omic studies of the human microbiome.
Primary Cilia Exhibit Mechanosensitivity to Cyclic Tensile Strain and Lineage-Dependent Expression in Adipose-Derived Stem Cells
Authors: Bodle Josephine , Hamouda Mehdi S. , Cai Shaobo , Williams Ramey B. , Bernacki Susan H. , Loboa Elizabeth G. 
Published: May 2019

AbstractNon-motile primary cilia are dynamic cellular sensory structures and are expressed in adipose-derived stem cells (ASCs). We have previously shown that primary cilia are involved in chemically-induced osteogenic differentiation of human ASC (hASCs) in vitro. Further, we have reported that 10% cyclic tensile strain (1 Hz, 4 hours/day) enhances hASC osteogenesis. We hypothesize that primary cilia respond to cyclic tensile strain in a lineage dependent manner and that their mechanosensitivity may regulate the dynamics of signaling pathways localized to the cilium. We found that hASC morphology, cilia length and cilia conformation varied in response to culture in complete growth, osteogenic differentiation, or adipogenic differentiation medium, with the longest cilia expressed in adipogenically differentiating cells. Further, we show that cyclic tensile strain both enhances osteogenic differentiation of hASCs while it suppresses adipogenic differentiation as evidenced by upregulation of RUNX2 gene expression and downregulation of PPARG and IGF-1, respectively. This study demonstrates that hASC primary cilia exhibit mechanosensitivity to cyclic tensile strain and lineage-dependent expression, which may in part regulate signaling pathways localized to the primary cilium during the differentiation process. We highlight the importance of the primary cilium structure in mechanosensing and lineage specification and surmise that this structure may be a novel target in manipulating hASC for in tissue engineering applications.
Anephrogenic phenotype induced by SALL1 gene knockout in pigs
Authors: Watanabe Masahito , Nakano Kazuaki , Uchikura Ayuko , Matsunari Hitomi , Yashima Sayaka , Umeyama Kazuhiro , Takayanagi Shuko , Sakuma Tetsushi , Yamamoto Takashi , Morita Sumiyo , Horii Takuro , Hatada Izuho , Nishinakamura Ryuichi , Nakauchi Hiromitsu , Nagashima Hiroshi 
Published: May 2019

AbstractTo combat organ shortage in transplantation medicine, a novel strategy has been proposed to generate human organs from exogenous pluripotent stem cells utilizing the developmental mechanisms of pig embryos/foetuses. Genetically modified pigs missing specific organs are key elements in this strategy. In this study, we demonstrate the feasibility of using a genome-editing approach to generate anephrogenic foetuses in a genetically engineered pig model. SALL1 knockout (KO) was successfully induced by injecting genome-editing molecules into the cytoplasm of pig zygotes, which generated the anephrogenic phenotype. Extinguished SALL1 expression and marked dysgenesis of nephron structures were observed in the rudimentary kidney tissue of SALL1-KO foetuses. Biallelic KO mutations of the target gene induced nephrogenic defects; however, biallelic mutations involving small in-frame deletions did not induce the anephrogenic phenotype. Through production of F1 progeny from mutant founder pigs, we identified mutations that could reliably induce the anephrogenic phenotype and hence established a line of fertile SALL1-mutant pigs. Our study lays important technical groundwork for the realization of human kidney regeneration through the use of an empty developmental niche in pig foetuses.
NMR metabolome of Borrelia burgdorferi in vitro and in vivo in mice
Authors: Glader Otto , Puljula Elina , Jokioja Johanna , Karonen Maarit , Sinkkonen Jari , Hytönen Jukka 
Published: May 2019

AbstractLyme borreliosis (LB), caused by bacteria of the Borrelia burgdorferi sensu lato (Borrelia) species, is the most common tick-borne infection in the northern hemisphere. LB diagnostics is based on clinical evaluation of the patient and on laboratory testing, where the main method is the detection of Borrelia specific antibodies in patient samples. There are, however, shortcomings in the current serology based LB diagnostics, especially its inability to differentiate ongoing infection from a previously treated one. Identification of specific biomarkers of diseases is a growing application of metabolomics. One of the main methods of metabolomics is nuclear magnetic resonance (NMR) spectroscopy. In the present study, our aim was to analyze whether Borrelia growth in vitro and infection in vivo in mice causes specific metabolite differences, and whether NMR can be used to detect them. For this purpose, we performed NMR analyses of in vitro culture medium samples, and of serum and urine samples of Borrelia infected and control mice. The results show, that there were significant differences in the concentrations of several amino acids, energy metabolites and aromatic compounds between Borrelia culture and control media, and between infected and control mouse serum and urine samples. For example, the concentration of L-phenylalanine increases in the Borrelia growth medium and in serum of infected mice, whereas the concentrations of allantoin and trigonelline decrease in the urine of infected mice. Therefore, we conclude that Borrelia infection causes measurable metabolome differences in vitro and in Borrelia infected mouse serum and urine samples, and that these can be detected with NMR.
Data modelling of converters for the automation and monitoring of MTDC grids
Authors: Roy Gaurav Kumar , Hu Jingxin , Sadu Abhinav , Ponci Ferdinanda , Monti Antonello , De Doncker Rik W. 
Published: May 2019

Multi‐terminal DC (MTDC) grids based on voltage source converters (VSCs) are a promising option to integrate the increasing share of generation from the distributed energy resources (DERs) both in the transmission and distribution grids. However, with the broader use of VSCs for the transmission and distribution grid, there is an absence of a standardised data model for the VSC. In this work, the authors propose an IEC 61850 based data model for VSCs and an existing IEC 61850 model is extended for the dual‐active bridge (DAB) converter as an interlink between various DC terminals and the modular multilevel converter (MMC). Furthermore, a generic data modelling guideline is proposed for intelligent electronic devices (IEDs), which are responsible for the interoperability among converters in the MTDC grid. The implementation of the real‐time monitoring system of a hybrid AC‐DC MTDC grid with the proposed IED is presented as an exemplary case. Through experimental tests of this MTDC grid, it is shown that the proposed IED meets the latency requirements for P2 through P6 class of monitoring, protection, and control applications according to the IEC 61850 standard. The automation architecture presented in this work is also validated for interoperability within the MTDC grid.
Quality assurance program of a nuclear facility
Authors: Leybman Dmitriy , Khripko Tatiana 
Published: May 2019

Quality Assurance Program (QAP, Program) is a standard, which regulates and coordinates activity, as well as determines quality assurance policy regarding services rendered and construction works conducted on nuclear infrastructure facilities. The Program must comply with the requirements of federal rules and regulations in the field of nuclear power engineering. The present QAP is available to all organisation employees carrying out works and rendering services during construction, reconstruction and major repairs of nuclear facilities as well as to experts conducting works and rendering services on a contract basis. The QAP implementation analysis and the evaluation of its results is conducted through internal audits. The implementation of the quality assurance program is provided through the following principles:
– the responsibility for quality assurance when conducting actual works and rendering services is imposed upon the task performer;
– precise segregation of duties and responsibilities between all contractors;
– regular control of compliance with regulations and developer’s requirements, as well as accurate documentation of the monitoring results;
– systematic update tracking for all official regulations and norms;
– the quality assurance methods incorporate the classification of equipment, systems and installation in terms of their impact on safety of nuclear facilities approved by official rules and regulations in the atomic energy sector.
Experimental research of punching shear mechanism of reinforcing concrete slab
Authors: Trekin Nikolay , Pekin Dmitrii 
Published: May 2019

The analysis of various regulatory methods for calculating reinforced concrete slabs for pushing and comparing with experiment results is made. The tested sample, measuring equipment and test bench are described. Sizes and materials for experimental prototype were chosen by existing beamless and capless slabs of monolithic reinforced concrete superstructures with column grid from 8×8 to 9×9 m.
Experimental research results of reinforcing concrete plate structure are presented for study purpose of stress-strain state when punching shear collapse occurring. Various aspects and observations obtained during the test are given. The comparison of the tested slab fragment with the complete response of slab structure is performed.
Analysis of tested sample stress-strain state and punching bearing capacity calculations results in according to existing regular standards were made. Main criterias of punching shear collapse were determined and new procedure for punching calculation of RC concrete slabs was offered basing on significantly new approach in punching bearing capacity defining.
Modeling Procedure of Coastal Protection Shaped Blocks with High Wave Suppressing and Interlocking Capacity
Authors: Iordanishvili Irina , Iremashvili Inga , Ujma Adam , Shurgaya Vladimer , Kandelaki Nodar , Iordanishvili Konstantin 
Published: May 2019

A groyne is a shore protection structure built perpendicular to the shoreline of the coast (or river), over the beach and into the shoreface (the area between the nearshore region and the inner continental shelf), to reduce longshore drift and trap sediments. A groyne field or system is a series of groynes acting together to protect a beach. Concret is often used as construction material.
On the basis of analysis of wave suppression efficiency and stability on the slope of more than one hundred existing shaped massives the new type of coast protecting reinforced concrete blocks – so called “Hexablock” (“Hexablock” was called because of its 6 facets) characterized with higher wave suppression properties, interlocking capacity, stability on the slope and longer life time is proposed.
Nehmen Depressionsdiagnosen bevölkerungsweit zu?
Authors: Thom Julia , Hoebel Jens , Nübel Julia , Kurth Tobias , Hapke Ulfert 
Published: May 2019

Zusammenfassung
Ziel der Studie Untersucht wird, ob sich die Zunahme ärztlicher Depressionsdiagnosen bevölkerungsweit zeigt und durch Veränderungen der Bevölkerungsstruktur erklären lässt.
Methode Stratifizierte Trendanalysen von Surveydaten aus 2009 und 2012 adjustiert für Bevölkerungsmerkmale.
Ergebnisse Die 12-Monats-Prävalenz einer ärztlichen Depressionsdiagnose steigt von 6,3 % auf 8,0 %. Der Trend erfolgt in allen Bevölkerungsgruppen. Bei Adjustierung sinkt er um 13,5 %.
Schlussfolgerung Der Prävalenzanstieg beschränkt sich nicht auf Risikogruppen und ist nur geringfügig in deren Entwicklung begründet.
Electrodynamics and 528 Frequency Resonance in Water Science Helps Solve the Mystery in Homeopathy
Authors: Horowitz Leonard G. 
Published: May 2019

AbstractScientific advances have increasingly credited water and its messaging capacity to explain many mysteries. Physical-chemical phenomena from genetic functions to intercellular communications have been found to rely on water structuring. Homeopathic researchers now advance related theories including quantum electrodynamics to solve the mystery of this profession's efficacy. Sceptics, however, continue to plague this healing profession. This article examines a generally overlooked foundational feature of water, its structuring and frequency electrodynamics that best explains the mysterious efficacy of homeopathy as well as why reproducibility in experimental outcomes are often unreliable. The ‘key’ that unlocks doors of understanding and demystifying this matter is the frequency central to giving life, sustaining health and rejuvenating nature—the oxygenating energy of 528-nm greenish-yellow light and its sonoluminescent predecessor-in-interest, 528-Hz frequency of sound. Quoting Hermes Trismegistus, ‘As above, so below, as within, so without, as the universe, so the soul…’. This article considers the consciousness and intentionality of homeopaths versus sceptics. This author proposes that the foundation of homeopathy and the solution to its mystery may be the ‘MI’ frequency of the original Solfeggio musical scale reputed to produce miracles, that is, 528 Hz.
Debulking Surgery Plus Radiation: Treatment Choice for Unresectable Stage III Thymic Carcinoma
Authors: Zhai Yirui , Hui Zhouguang , Gao Yushun , Liang Jun , Zhou Zongmei , Wang Luhua , Feng Qinfu 
Published: May 2019

Background Total resection may not be achieved in patients with thymic carcinoma, particularly those with Masaoka stage III disease. Debulking surgery plus postoperative radiotherapy and radiation alone are treatment options for such patients. We aimed to compare the overall survival (OS) between patients with thymic carcinoma who underwent debulking surgery plus postoperative radiotherapy and those who underwent radiation alone.
Methods This was a single-center retrospective study of patients histologically diagnosed as having Masaoka stage III thymic carcinoma between January 1980 and January 2010. Patients were classified into the following groups according to treatments received: debulking surgery plus radiotherapy (group A) and radiotherapy alone (group B). Data on demographics, histology, invasion, radiotherapy, chemotherapy, and survival were collected. Survival time was calculated and compared between the groups using the Kaplan–Meier method. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
Results Of the 47 enrolled patients, 26 and 21 patients were categorized into groups A and B, respectively. There are no significant differences in the Eastern Cooperative Oncology Group performance status score, histological type, great vessel invasion, and chemotherapy proportion between the groups. The median radiation dose was 60 Gy in both groups. The 5-year OS rates were 54.4 and 0% in groups A and B, respectively (p = 0.019). No operation-induced mortality was recorded.
Conclusion For patients with unresectable Masaoka stage III disease, debulking surgery with radiotherapy is preferred, as this was proven to be more efficient than the radiation-alone procedure.
Potential of an Electronic Health Record-Integrated Patient Portal for Improving Care Plan Concordance during Acute Care
Authors: Dalal Anuj K. , Dykes Patricia , Samal Lipika , McNally Kelly , Mlaver Eli , Yoon Cathy S. , Lipsitz Stuart R. , Bates David W. 
Published: May 2019

Background Care plan concordance among patients and clinicians during hospitalization is suboptimal.
Objective This article determines whether an electronic health record (EHR)-integrated patient portal was associated with increased understanding of the care plan, including the key recovery goal, among patients and clinicians in acute care setting.
Methods The intervention included (1) a patient portal configured to solicit a single patient-designated recovery goal and display the care plan from the EHR for participating patients; and (2) an electronic care plan for all unit-based nurses that displays patient-inputted information, accessible to all clinicians via the EHR. Patients admitted to an oncology unit, including their nurses and physicians, were enrolled before and after implementation. Main outcomes included mean concordance scores for the overall care plan and individual care plan elements.
Results Of 457 and 283 eligible patients approached during pre- and postintervention periods, 55 and 46 participated in interviews, respectively, including their clinicians. Of 46 postintervention patients, 27 (58.7%) enrolled in the patient portal. The intention-to-treat analysis demonstrated a nonsignificant increase in the mean concordance score for the overall care plan (62.0–67.1, adjusted p = 0.13), and significant increases in mean concordance scores for the recovery goal (30.3–57.7, adjusted p < 0.01) and main reason for hospitalization (58.6–79.2, adjusted p < 0.01). The on-treatment analysis of patient portal enrollees demonstrated significant increases in mean concordance scores for the overall care plan (61.9–70.0, adjusted p < 0.01), the recovery goal (30.4–66.8, adjusted p < 0.01), and main reason for hospitalization (58.3–81.7, adjusted p < 0.01), comparable to the intention-to-treat analysis.
Conclusion Implementation of an EHR-integrated patient portal was associated with increased concordance for key care plan components. Future efforts should be directed at improving concordance for other care plan components and conducting larger, randomized studies to evaluate the impact on key outcomes during transitions of care.
Clinical Trials Identifier NCT02258594.
Transcending the moment
Authors: Power Martin J. , Dillane Aileen 
Published: May 2019

Abstract
Our paper argues that British singer Billy Bragg performs protest songs that cleverly draw
upon musical forms underpinning his positioning as a voice of, and for, the ordinary person, ultimately
disenfranchised by governmental adherence to neoliberal policies. While political songs are a product of their
time, many of them can also transcend that historical moment and have a longer shelf-life in terms of their
capacity to inform political thinking and action. Our song(s) of choice in this paper do so not just in terms
of the relevance of their ‘literal’ message but also in how they draw upon traditional structures of feeling
and generic elements of folk song to underpin this sense of ‘grass-roots’ critique via a modified, acoustic
ballad form and a performance style. This serves to authenticate and legitimate the singer and his message
and, in turn, allows Bragg to accumulate political and cultural capital.