bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac resynchronization therapy with a defibrillator (CRTd) in failing heart patients with type 2 diabetes mellitus and treated by glucagon-like peptide 1 receptor agonists (GLP-1 RA) therapy vs. conventional hypoglycemic drugs: arrhythmic burden, hospitalizations for heart failure, and CRTd responders rate
Authors: Sardu Celestino , Paolisso Pasquale , Sacra Cosimo , Santamaria Matteo , de Lucia Claudio , Ruocco Antonio , Mauro Ciro , Paolisso Giuseppe , Rizzo Maria Rosaria , Barbieri Michelangela , Marfella Raffaele 
Published: October 2018

Abstract
Objectives
To evaluate clinical outcomes in patients with diabetes, treated by cardiac resynchronization therapy with a defibrillator (CRT-d), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) in addition to conventional hypoglycemic therapy vs. CRTd patients under conventional hypoglycemic drugs.

Background
Patients with diabetes treated by CRTd experienced an amelioration of functional New York Association Heart class, reduction of hospital admissions, and mortality, in a percentage about 60%. However, about 40% of CRTd patients with diabetes experience a worse prognosis.

Materials and methods
We investigated the 12-months prognosis of CRTd patients with diabetes, previously treated with hypoglycemic drugs therapy (n 271) vs. a matched cohort of CRTd patients with diabetes treated with GLP-1 RA in addition to conventional hypoglycemic therapy (n 288).

Results
At follow up CRTd patients with diabetes treated by GLP-1 RA therapy vs. CRTd patients with diabetes that did not receive GLP-1 RA therapy, experienced a significant reduction of NYHA class (p value < 0.05), associated to higher values of 6 min walking test (p value < 0.05), and higher rate of CRTd responders (p value < 0.05). GLP-1 RA patients vs. controls at follow up end experienced lower AF events (p value < 0.05), lower VT events (p value < 0.05), lower rate of hospitalization for heart failure worsening (p value < 0.05), and higher rate of CRTd responders (p value < 0.05). To date, GLP-1 RA therapy may predict a reduction of AF events (HR 0.603, CI [0.411–0.884]), VT events (HR 0.964, CI [0.963–0.992]), and hospitalization for heart failure worsening (HR 0.119, CI [0.028–0.508]), and a higher CRT responders rate (HR 3.707, CI [1.226–14.570]).

Conclusions
GLP-1 RA drugs in addition to conventional hypoglycemic therapy may significantly reduce systemic inflammation and circulating BNP levels in CRTd patients with diabetes, leading to a significant improvement of LVEF and of the 6 min walking test, and to a reduction of the arrhythmic burden. Consequently, GLP-1 RA drugs in addition to conventional hypoglycemic therapy may reduce hospital admissions for heart failure worsening, by increasing CRTd responders rate.
Trial registration NCT03282136. Registered 9 December 2017 “retrospectively registered”
Clinical Utility of Genomic Profiling in the Treatment of Advanced Sarcomas: A Single-Center Experience
Authors: Boddu Spandana , Walko Christine M. , Bienasz Stephanie , Bui Marilyn M. , Henderson-Jackson Evita , Naghavi Arash O. , Mullinax John E. , Joyce David M. , Binitie Odion , Letson G. Douglas , Gonzalez Ricardo J. , Reed Damon R. , Druta Mihaela , Brohl Andrew S. 
Published: October 2018

Purpose
Sarcomas are a diverse group of malignant tumors that arise from soft tissues or bone. For most advanced cases, there is a substantial need for improved therapeutic options and, therefore, a desire to more precisely tailor therapy in individual cases. In this study, we review our institutional experience with next-generation sequencing (NGS)–based molecular profiling for non–GI stromal tumors sarcomas, with a focus on the clinical utility of the results.

Patients and Methods
We retrospectively analyzed results of NGS performed on tumors from 114 patients with a diagnosis of sarcoma. A chart review was conducted to review the clinical impact of NGS findings.

Results
A median of three putatively oncogenic gene alterations were identified per tumor sample (range, 0 to 19) and at least one mutation was detected in 96.7% of tumors. Fifty-six patients (49.1%) harbored a finding that was felt to be actionable after review by a molecular tumor board. Five patients (4.4%) had a diagnosis change as a result of NGS findings. In 15 patients (13.2%), therapeutic selection was influenced by NGS findings. Four of 15 (26.7%) of the NGS-influenced systemic therapies resulted in clinical benefit.

Conclusion
Putatively oncogenic mutations are readily detected in the majority of sarcomas. Genetic profiling affected the diagnosis and/or treatment approach in a sizeable minority of patients with sarcoma treated at our center. Additional study is required to determine if genetic profiling leads to improved clinical outcomes.
Characterization and in ovo vascularisation of a 3D-printed hydroxyapatite scaffold with different extracellular matrix coatings under perfusion culture
Authors: Burgio Floriana , Rimmer Natalie , Pieles Uwe , Buschmann Johanna , Beaufils-Hugot Marina 
Published: October 2018

For the fabrication of appropriate bone tissue engineered constructs, several prerequisites should be fulfilled. It should offer long-term stability, allow proper cell attachment and proliferation, furthermore be osteoinductive and easy to be vascularized. Having these requirements as background, we fabricated a novel porous 3D-printed hydroxyapatite (HA) scaffold and treated it with oxygen plasma (OPT). MG-63 pre-osteoblast-seeded bone constructs allowed good cell attachment and proliferation, even better when cultivated in a perfusion flow bioreactor. Moreover, the deposition of extracellular matrix (ECM) on the otherwise inorganic surface changed the mechanical properties in a favourable manner: elasticity increased from 42.95±1.09 to 91.9±5.1 MPa (assessed by nanoindentation). Compared to static conditions, osteogenic differentiation was enhanced in the bioreactor, with upregulation ALP, collagen I and osteocalcin gene expression.
In parallel experiments, primary human bone marrow mesenchymal stromal cells (hBMSCs) were used and findings under dynamic conditions were similar; with a higher commitment towards osteoblasts compared to static conditions. In addition, angiogenic markers CD31, eNOS and VEGF were upregulated, especially when osteogenic medium was used compared to proliferative medium. To compare differently fabricated ECMs in terms of vascularisation, decellularized constructs were tested in the chorioallantoic membrane (CAM) assay with subsequent assessment of the functional perfusion capacity by MRI in the living chick embryo. Here, vascularisation induced by ECM from osteogenic medium led to a vessel distribution more homogenously throughout the construct, while ECM from proliferative medium enhanced vessel density at the interface and to a lower extent at the middle and top. We conclude that dynamic cultivation of a novel porous OPT HA scaffold with hBMSCs in osteogenic medium and subsequent decellularization provides a promising off-the-shelf bone tissue engineered construct.
RPSA, a candidate gene for isolated congenital asplenia, is required for pre-rRNA processing and spleen formation in Xenopus
Authors: Griffin John N. , Sondalle Samuel B. , Robson Andrew , Mis Emily K. , Griffin Gerald , Kulkarni Saurabh S. , Deniz Engin , Baserga Susan J. , Khokha Mustafa K. 
Published: October 2018

ABSTRACT
A growing number of tissue-specific inherited disorders are associated with impaired ribosome production, despite the universal requirement for ribosome function. Recently, mutations in RPSA, a protein component of the small ribosomal subunit, were discovered to underlie approximately half of all isolated congenital asplenia cases. However, the mechanisms by which mutations in this ribosome biogenesis factor lead specifically to spleen agenesis remain unknown, in part due to the lack of a suitable animal model for study. Here we reveal that RPSA is required for normal spleen development in the frog, Xenopus tropicalis. Depletion of Rpsa in early embryonic development disrupts pre-rRNA processing and ribosome biogenesis, and impairs expression of the key spleen patterning genes nkx2-5, bapx1 and pod1 in the spleen anlage. Importantly, we also show that whereas injection of human RPSA mRNA can rescue both pre-rRNA processing and spleen patterning, injection of human mRNA bearing a common disease-associated mutation cannot. Together, we present the first animal model of RPSA-mediated asplenia and reveal a crucial requirement for RPSA in pre-rRNA processing and molecular patterning during early Xenopus development.
Mathematical Features of the Genealogy of Acyclic Conjugated Polyenes
Authors: Hosoya Haruo 
Published: October 2018

Abstract
For the acyclic conjugated polyenes of N ≤ 12 fairly good correlation between the HMO Eπ and topological index Z is demonstrated and analyzed mathematically. By using a much simpler index, mean length of conjugation L, relative stability among the isomers can roughly be anticipated and understood even by beginners of chemistry. The genealogy of the acyclic conjugated polyene family is obtained and interpreted by drawing systematic diagrams growing from ethylene by using the four modes, i.e., elongation, inner and outer branching, and horn growing. The definition and importance of cross-conjugation in organic chemistry is discussed.
Molecular identification and phylogenetic analysis of GABA-producing lactic acid bacteria isolated from indigenous dadih of West Sumatera, Indonesia
Authors: Anggraini Lili , Marlida Yetti , Wizna Wizna , Jamsari Jamsari , Mirzah Mirzah , Adzitey Frederick , Huda Nurul 
Published: October 2018

Background: Dadih (fermented buffalo milk) is a traditional Indonesian food originating from West Sumatra province. The fermentation process is carried out by lactic acid bacteria (LAB), which are naturally present in buffalo milk. Lactic acid bacteria have been reported as one of potential producers of γ-aminobutyric acid (GABA). GABA acts as a neurotransmitter inhibitor of the central nervous system. Methods: In this study, molecular identification and phylogenetic analysis of GABA producing LAB isolated from indigenous dadih of West Sumatera were determined. Identification of the GABA-producing LAB DS15 was based on conventional polymerase chain reaction. 16S rRNA gene sequence analysis was used to identify LAB DS15. Results: PCR of the 16S rRNA gene sequence of LAB DS15 gave an approximately 1400 bp amplicon. Phylogenetic analysis showed that LAB DS15 was Pediococcus acidilactici, with high similarity of 99% at 100% query coverage to Pediococcus acidilactici strain DSM 20284. Conclusions: It can be concluded that GABA producing LAB isolated from indigenous dadih was Pediococcus acidilactici.
The disentanglement of Andreaea alpina Hedw. (Andreaeaceae): Typifications and nomenclatural changes
Authors: Price Michelle J. , Ellis Leonard T. 
Published: October 2018

AbstractThe name Andreaea alpina was validly published in Hedwig’s 1801 work Species muscorum frondosorum, but the entity itself can be traced back in the pre‐Linnaean literature to Dillenius of 1741 where it was described under “Lichenastrum”. Three hebarium sheets in the Hedwig‐Schwägrichen Herbarium in G are associated with A. alpina: one that was identified as A. rupestris (G00056451), one as A. obovata (G00056454), and one non‐original specimen that was indicated as A. alpina (G00040015). The latter sheet had been annotated “holotype”, and later “lectotype”, for this name, although formal typification of the name has yet to be effected via publication. To clarify the confusion over the true identity of the material in G and thus over the correct application of the name Andreaea alpina, a lectotype is designated herein from the original material in the Hedwig Herbarium. The chosen material corresponds most closely to the validating description and represents material that was seen by Hedwig for his 1801 work. In consequence of this typification, the name Andreaea hookeri is proposed for the entity that had erroneously come to be known as Andreaea alpina.
Innovative Technologies of Pre-Shift Psychophysiological Control of Personnel as Means of Increasing Safety of Radiation and Nuclear Enterprises and Objects of the State Atomic Energy Corporation ROSATOM
Authors: Бобров Александр , Bobrov Alexandr , Иванов В. , Ivanov V. , Калинина М. , Kalinina M. , Новикова Т. , Novikova T. , Ратаева В. , Rataeva V. , Седин В. , Sedin V. , Щебланов В. , Shcheblanov V. , Щелканова Е. , Shchelkanova E. , Самойлов Александр , Samoylov Alyeksandr 
Published: October 2018

Purpose: Validation of requirements to the hardware and software of pre-shift psychophysiological monitoring and assessment of effectiveness of use of technology of the vibraimage at pre-shift psychophysiological control of personnel of radiation and nuclear dangerous enterprises and objects of the State Atomic Energy Corporation ROSATOM.
Material and methods: Pre-shift psychophysiological control of employees of Elektrochimpribor plant (20 people) and the Northwest Center for Radioactive Waste Management “SevRAO” , a Branch of FSUE RosRAO, Zaozersk of Murmansk region (18 workers of facilities for management of spent nuclear fuel and radioactive waste). Pre-shift psychophysiological monitoring was carried out within 3 months. During the research measurement of arterial blood pressure, assessment of health, activity and mood was taken. The psychophysiological condition was estimated according to innovative technology of the vibraimage with the use of the Vibrastaff program.
Results: Reliability improvement of a human factor is one of the main ways of improving radiation and nuclear safety of the facilities and objects of the State Atomic Energy Corporation ROSATOM. It demands improving methods and means of psychophysiological providing. First of all methods, tools and criteria of pre-shift psychophysiological control. The developed requirements to the hardware and software of pre-shift psychophysiological monitoring and innovative technology of assessment of parameters of the vibraimage allow quickly (within 1 minute) to receive the decision on the admission / not the admission to work. Its practical use gives the chance, according to pre-shift psychophysiological control in due time, to accept organizational, medical and other administrative decisions for improving radiation and nuclear safety of the enterprises and objects of the State Atomic Energy Corporation ROSATOM.
Self-Control Formation of Younger Schoolchildren When Conducting Training Dictations in Russian Lessons
Authors: Соснина Е. , Sosnina E. 
Published: October 2018

The article deals with the problem of the development of self-control among younger schoolchildren. The formation of self-control must begin from the first months of schooling, in particular at the initial stage of learning writing taking dictation, it is important to establish the ability to control what is written. The article presents a model for the development of self-control among younger schoolchildren as a factor in the successful self-test of dictation. The examples of the forms and methods of work in the first and second grades are given, which help to carry out the current
and final control when younger schoolchildren write teaching dictations.
A Mendelian Randomization-Based Approach to Identify Early and Sensitive Diagnostic Biomarkers of Disease
Authors: Mohammadi-Shemirani Pedrum , Sjaarda Jennifer , Gerstein Hertzel C , Treleaven Darin J , Walsh Michael , Mann Johannes F , McQueen Matthew J , Hess Sibylle , Paré Guillaume 
Published: October 2018

Abstract

BACKGROUND
Identifying markers of chronic kidney disease (CKD) that occur early in the disease process and are specific to loss of kidney function rather than other underlying causes of disease may allow earlier, more accurate identification of patients who will develop CKD. We therefore sought to identify diagnostic blood markers of early CKD that are caused by loss of kidney function by using an innovative “reverse Mendelian randomization” (MR) approach.

METHODS
We applied this technique to genetic and biomarker data from 4147 participants in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial, all with known type 2 diabetes, impaired fasting glucose, or impaired glucose tolerance. Two-sample MR was conducted using variants associated with creatinine-based eGFR (eGFRcrea) from the CKDGen Consortium (n = 133814) to estimate the effect of genetically decreased eGFRcrea on 238 serum biomarkers.

RESULTS
With reverse MR, trefoil factor 3 (TFF3) was identified as a protein that is increased owing to decreased eGFRcrea (β = 1.86 SD per SD decrease eGFRcrea; 95% CI, 0.95–2.76; P = 8.0 × 10−5). Reverse MR findings were consistent with epidemiological associations for incident CKD in ORIGIN (OR = 1.28 per SD increase in TFF3; 95% CI, 1.18–1.38; P = 4.58 × 10−10). Addition of TFF3 significantly improved discrimination for incident CKD relative to eGFRcrea alone (net reclassification improvement = 0.211; P = 9.56 × 10−12) and in models including additional risk factors.

CONCLUSIONS
Our results suggest TFF3 is a valuable diagnostic marker for early CKD in dysglycemic populations and acts as a proof of concept for the application of this novel MR technique to identify diagnostic biomarkers for other chronic diseases.

ClinicalTrials.gov Identifier
NCT00069784
A retórica da pós-verdade
Authors: De Campos Marcella Machado , De Souza e Silva Maria Cecília Pérez 
Published: October 2018

O objetivo deste artigo é problematizar o “fenômeno da pós-verdade”, escolhida como a palavra do ano de 2016 pela Oxford Dictionaries, mais especificamente, seu potencial de se instaurar como desmemória discursiva (PAVEAU, 2013a, 2015) como correlato de alienação da verdade na produção de narrativas fantasiosas que repercutem na sociedade democrática contemporânea. Tal qual introduzida por Paveau partindo do conceito de memória discursiva proposto por Courtine, a noção de desmemória discursiva se caracteriza pelo desvio de um sentido primeiro cujo efeito favorece, para além do enunciador implicado naquele discurso, dada conjuntura. A partir de duas declarações polêmicas, uma de Donald Trump e outra de Kellyanne Conway, conselheira da Casa Branca, foram analisadas, sob o pano de fundo de uma crise de representatividade política em nível mundial, as manobras enunciativas empreendidas pelos respectivos enunciadores, permitindo depreender que a desmemória discursiva, seja por retificação ou ressignificação, opera como um dos recursos argumentativos no bojo da linguagem que assegura à pós-verdade o status de novo normal na atualidade.
Intraokuläres Melanom bei einer 10 Jahre alten Lamastute (Lama glama)
Authors: Voigt Katja , Falkenau Almuth , Herbach Nadja , Feist Melanie , Tschoner Theresa 
Published: October 2018

ZusammenfassungEine 10-jährige Lamastute wurde mit einer chronisch wuchernden Masse des linken Auges vorgestellt. Das Tier zeigte einen linksseitigen Exophthalmus, die Nickhaut war gerötet. Die Hornhaut war von einer gelblich-rötlichen, undurchsichtigen Gewebsmasse bedeckt und wies ulzerative Veränderungen auf. Die tieferen Strukturen des Auges ließen sich nicht beurteilen. Das rechte Auge stellte sich unauffällig dar. Das linke Auge wurde unter Allgemeinanästhesie entfernt. Die histopathologische Untersuchung des Exstirpats ergab ein okuläres amelanotisches Melanom. Kornea, Sklera, Glaskörper und Linse waren nicht mehr zu identifizieren. Vierzehn Monate später wurde das Lama mit einer Umfangsvermehrung im Bereich der linken Orbita und Blindheit auf dem rechten Auge eingeliefert und aufgrund des schlechten Allgemeinzustands eingeschläfert. Bei der pathologisch-anatomischen und histopathologischen Untersuchung wurde ein Rezidiv des amelanotischen Melanoms mit Metastasierung in die regionären Lymphknoten unter Mitbeteiligung des Nervus opticus festgestellt, was die Blindheit des rechten Auges erklärte.
Platelet Microparticles Mediate Glomerular Endothelial Injury in Early Diabetic Nephropathy
Authors: Zhang Yang , Ma Kun Ling , Gong Yu Xiang , Wang Gui Hua , Hu Ze Bo , Liu Liang , Lu Jian , Chen Pei Pei , Lu Chen Chen , Ruan Xiong Zhong , Liu Bi Cheng 
Published: October 2018

Background
Glomerular endothelium dysfunction, which plays a crucial role in the pathogenesis of early diabetic nephropathy, might be caused by circulating metabolic abnormalities. Platelet microparticles, extracellular vesicles released from activated platelets, have recently emerged as a novel regulator of vascular dysfunction.

Methods
We studied the effects of platelet microparticles on glomerular endothelial injury in early diabetic nephropathy in rats with streptozotocin-induced diabetes and primary rat glomerular endothelial cells. Isolated platelet microparticles were measured by flow cytometry.

Results
Plasma platelet microparticles were significantly increased in diabetic rats, an effect inhibited in aspirin-treated animals. In cultured glomerular endothelial cells, platelet microparticles induced production of reactive oxygen species, decreased nitric oxide levels, inhibited activities of endothelial nitric oxide synthase and SOD, increased permeability of the glomerular endothelium barrier, and reduced thickness of the endothelial surface layer. Conversely, inhibition of platelet microparticles in vivo by aspirin improved glomerular endothelial injury. Further analysis showed that platelet microparticles activated the mammalian target of rapamycin complex 1 (mTORC1) pathway in glomerular endothelial cells; inhibition of the mTORC1 pathway by rapamycin or raptor siRNA significantly protected against microparticle-induced glomerular endothelial injury in vivo and in vitro. Moreover, platelet microparticle–derived chemokine ligand 7 (CXCL7) contributed to glomerular endothelial injury, and antagonizing CXCL7 using CXCL7-neutralizing antibody or blocking CXCL7 receptors with a competitive inhibitor of CXCR1 and CXCR2 dramatically attenuated such injury.

Conclusions
These findings demonstrate a pathogenic role of platelet microparticles in glomerular endothelium dysfunction, and suggest a potential therapeutic target, CXCL7, for treatment of early diabetic nephropathy.