bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short QT in a Cohort of 1.7 Million Persons: Prevalence, Correlates, and Prognosis
Authors: Iribarren Carlos , Round Alfred D. , Peng Jonathan A. , Lu Meng , Klatsky Arthur L. , Zaroff Jonathan G. , Holve Taylor J. , Prasad Amit , Stang Paul 
Published: May 2014

BackgroundShort QT syndrome (QTc ≤ 300 ms) is a novel hereditary channelopathy linked to syncope, paroxysmal atrial fibrillation, and sudden cardiac death. However, its epidemiological features remain unsettled.Objectives(1) To assess the prevalence of short QT in a large population‐based sample; (2) to evaluate its demographic and clinical correlates and; (3) to determine its prognosis.MethodsA database of 6.4 million electrocardiograms (ECGs) obtained between 1995 and 2008 among 1.7 million persons was used. An internal, population‐based method for heart rate correction (QTcreg) was used and all ECGs with QTcreg ≤300 ms were manually validated. Linked health plan databases were used for covariate and survival ascertainment.ResultsOf 6,387,070 ECGs, 1086 had an ECG with machine‐read QTcreg ≤300 ms. Only 4% (45/1086) were validated yielding a prevalence of 0.7 per 100,000 or 1 of 141,935 ECGs. At the person level, the overall prevalence of QTcreg ≤300 ms was 2.7 per 100,000 or 1 of 37,335. The factors independently and significantly associated with validated QTcreg ≤300 ms were age over 65 years, Black race, prior history of ventricular dysrhythmias, chronic obstructive pulmonary disease, ST‐T abnormalities, ischemia, bigeminy pattern, and digitalis effect. After 8.3 years of median follow‐up and relative to normal QTcreg, validated QTcreg ≤300 ms was associated after multivariate adjustment with a 2.6‐fold (95% confidence interval [CI] = 1.9–3.7) increased risk of death.ConclusionQTcreg ≤300 ms was extraordinarily rare and was associated with significant ECG abnormalities and reduced survival.
Rationale, design, and method of the Diabetes & Women's Health study – a study of long‐term health implications of glucose intolerance in pregnancy and their determinants
Authors: Zhang Cuilin , Hu Frank B. , Olsen Sjurdur F. , Vaag Allan , Gore‐Langton Robert , Chavarro Jorge E. , Bao Wei , Yeung Edwina , Bowers Katherine , Grunnet Louise G. , Sherman Seth , Kiely Michele , Strøm Marin , Hansen Susanne , Liu Aiyi , Mills James , Fan Ruzong ,   the DWH study team
Published: May 2014

AbstractWomen who develop gestational diabetes mellitus or impaired glucose tolerance during pregnancy are at substantially increased risk for type 2 diabetes and comorbidities after pregnancy. Little is known about the role of genetic factors and their interactions with environmental factors in determining the transition from gestational diabetes mellitus to overt type 2 diabetes mellitus. These critical data gaps served as the impetus for this Diabetes & Women's Health study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health interventions in relation to the transition of gestational diabetes mellitus to type 2 diabetes mellitus. To achieve the goal efficiently, we are applying a hybrid design enrolling and collecting data longitudinally from approximately 4000 women with a medical history of gestational diabetes mellitus in two existing prospective cohorts, the Nurses' Health Study II and the Danish National Birth Cohort. Women who had a medical history of gestational diabetes mellitus in one or more of their pregnancies are eligible for the present study. After enrollment, we follow study participants for an additional 2 years to collect updated information on major clinical and environmental factors that may predict type 2 diabetes mellitus risk as well as with biospecimens to measure genetic and biochemical markers implicated in glucose metabolism. Newly collected data will be appended to the relevant existing data for the creation of a new database inclusive of genetic, epigenetic and environmental data. Findings from the study are critical for the development of targeted and more effective strategies to prevent type 2 diabetes mellitus and its complications in this high‐risk population.
A learning model for enhancing the student's control in educational process using Web 2.0 personal learning environments
Authors: Rahimi Ebrahim , van den Berg Jan , Veen Wim 
Published: May 2014

AbstractIn recent educational literature, it has been observed that improving student's control has the potential of increasing his or her feeling of ownership, personal agency and activeness as means to maximize his or her educational achievement. While the main conceived goal for personal learning environments (PLEs) is to increase student's control by taking advantage of Web 2.0 tools and technologies, there is not a robust learning model available to achieve it. This contribution focuses on proposing a learning model built upon self‐regulated learning and student's control theories and concepts, and supported by the learning affordances of Web 2.0 tools and technologies for enhancing student's control by developing and applying Web 2.0 PLEs.
Differences in 24‐h urine composition between nephrolithiasis patients with and without diabetes mellitus
Authors: Hartman Christopher , Friedlander Justin I. , Moreira Daniel M. , Elsamra Sammy E. , Smith Arthur D. , Okeke Zeph 
Published: May 2014

ObjectivesTo examine the differences in 24‐h urine composition between nephrolithiasis patients with and without diabetes mellitus (DM) in a large cohort of stone‐formers and to examine differences in stone composition between patients with and without DM.Patients and MethodsA retrospective review of 1117 patients with nephrolithiasis and a 24‐h urine analysis was completed. Univariable analysis of 24‐h urine profiles and multivariable linear regression models were performed, comparing patients with and without DM. A subanalysis of patients with stone analysis data available was performed, comparing the stone composition of patients with and without DM.ResultsOf the 1117 patients who comprised the study population, 181 (16%) had DM and 936 (84%) did not have DM at the time of urine analysis. Univariable analysis showed significantly higher total urine volume, citrate, uric acid (UA), sodium, potassium, sulphate, oxalate, chloride, and supersaturation (SS) of UA in individuals with DM (all P < 0.05). However, patients with DM had significantly lower SS of calcium phosphate and pH (all P < 0.05). Multivariable analysis showed that patients with DM had significantly lower urinary pH and SS of calcium phosphate, but significantly greater citrate, UA, sulphate, oxalate, chloride, SSUA, SS of calcium oxalate, and volume than patients without DM (all P < 0.05). Patients with DM had a significantly greater proportion of UA in their stones than patients without DM (50.2% vs 13.5%, P < 0.001).ConclusionsDM was associated with multiple differences on 24‐h urine analysis compared with those without DM, including significantly higher UA and oxalate, and lower pH. Control of urinary UA and pH, as well as limiting intake of dietary oxalate may reduce stone formation in patients with DM.
Pattern of resolution of pulmonary hypertension, long‐term allograft right ventricular function, and exercise capacity in high‐risk heart transplant recipients listed under oral sildenafil
Authors: De Santo Luca S. , Buonocore Marianna , Agrusta Federica , Bancone Ciro , Galdieri Nicola , Romano Gianpaolo , Maiello Ciro , Amarelli Cristiano 
Published: May 2014

AbstractUnresponsive pulmonary hypertension (PH) implies poor posttransplant outcomes. Data on late adaptation of the right ventricle (RV) are still few. This study evaluated three‐yr RV function and remodeling, exercise capacity, and hemodynamic data in a selected group of patients initially disqualified because of PH. Between May 2005 and December 2009, 31 consecutive patients were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12‐wk trial, RHC disclosed PH reversibility (mean PVR: 5.41 ± 3 Wood units, mean TPG 14.5 ± 5.6 mmHg, and mean systolic PAP 68.9 ± 15.1 mmHg), allowing listing even though as high‐risk procedures. All patients underwent heart transplantation. RV failure developed in three patients (9.6%), and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary hemodynamic profile normalization within the third postoperative month, allowing weaning from sildenafil in the 30 hospital survivors. One‐ and three‐yr RHCs confirmed stable PH reversal (n = 26, all three‐yr survivors). Parameters of late RV function and remodeling proved satisfactory. Parameters of functional capacity (Vo2 peak 19.7 ± 3.6 mL/kg/min and slope VE/Vco2 34.8 ± 2.7) proved homogeneous to those measured in transplant recipients with normal preoperative pulmonary artery pressure. Oral sildenafil is effective in allowing candidacy, safe transplantation, and long‐term survival in PH recipients initially disqualified.
Dermatoscopy of amelanotic and hypomelanotic melanoma
Authors: Stojkovic‐Filipovic Jelena , Kittler Harald 
Published: May 2014

SummaryAmelanotic melanoma is a subtype of cutaneous melanoma without pigment. The clinical diagnosis is challenging because it may mimic benign or malignant melanocytic and non‐melanocytic neoplasms and inflammatory skin diseases. In synchrony with the improvement of the diagnosis of pigmented lesions, dermatoscopy may assist the clinician in the diagnosis of non‐pigmented skin neoplasms in general and of amelanotic melanoma in particular. We have searched the literature to extract the most relevant dermatoscopic clues to diagnose amelanotic and hypomelanotic melanomas by dermatoscopy. In addition we present eight consecutive cases and discuss their clinical and dermatoscopic characteristics in the light of published data.
Phylogenetic diversity, habitat loss and conservation in South American pitvipers (Crotalinae: Bothrops and Bothrocophias)
Authors: Fenker Jéssica , Tedeschi Leonardo G. , Pyron Robert Alexander , Nogueira Cristiano de C. 
Published: May 2014

AbstractAimTo analyze impacts of habitat loss on evolutionary diversity and to test widely used biodiversity metrics as surrogates for phylogenetic diversity, we study spatial and taxonomic patterns of phylogenetic diversity in a wide‐ranging endemic Neotropical snake lineage.LocationSouth America and the Antilles.MethodsWe updated distribution maps for 41 taxa, using species distribution models and a revised presence‐records database. We estimated evolutionary distinctiveness (ED) for each taxon using recent molecular and morphological phylogenies and weighted these values with two measures of extinction risk: percentages of habitat loss and IUCN threat status. We mapped phylogenetic diversity and richness levels and compared phylogenetic distances in pitviper subsets selected via endemism, richness, threat, habitat loss, biome type and the presence in biodiversity hotspots to values obtained in randomized assemblages.ResultsEvolutionary distinctiveness differed according to the phylogeny used, and conservation assessment ranks varied according to the chosen proxy of extinction risk. Two of the three main areas of high phylogenetic diversity were coincident with areas of high species richness. A third area was identified only by one phylogeny and was not a richness hotspot. Faunal assemblages identified by level of endemism, habitat loss, biome type or the presence in biodiversity hotspots captured phylogenetic diversity levels no better than random assemblages. Pitvipers found in the richest areas or included in the IUCN Red List showed significant phylogenetic clustering.Main conclusionsUsual biodiversity metrics were unable to adequately represent spatial patterns of evolutionary diversity in pitvipers. Current Red List status fails to properly represent evolutionary distinctiveness in the group. Phylogenetic diversity is unevenly distributed even within biodiversity hotspots, and species‐poor areas may harbour high phylogenetic diversity. This reinforces the need for targeted and spatially accurate approaches for adequately representing evolutionary processes in conservation planning.
Cardiovascular safety of combination therapies with incretin‐based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study
Authors: Mogensen U. M. , Andersson C. , Fosbøl E. L. , Schramm T. K. , Vaag A. , Scheller N. M. , Torp‐Pedersen C. , Gislason G. , Køber L. 
Published: May 2014

AimDipeptidyl peptidase‐4 (DPP‐4) inhibitors and glucagon‐like peptide‐1 (GLP‐1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long‐term safety compared with conventional combination therapies are limited.MethodsDanish individuals without prior myocardial infarction or stroke that initiated combinations of metformin with sulphonylurea (SU), DPP‐4 inhibitors, GLP‐1 agonists or insulin between 9 May 2007 and 31 December 2011 were followed up for the risk of all‐cause mortality, cardiovascular (CV) mortality or a combined end point of myocardial infarction, stroke and CV mortality. Rate ratios (RR) were calculated using time‐dependent multivariable Poisson regression analysis.ResultsA total of 40 028 patients (59% men, mean age 60 ± 13 years) used metformin with SU (n = 25 092), DPP‐4 inhibitor (n = 11 138), GLP‐1 agonist (n = 4345) or insulin (n = 6858). Crude incidence rates per 1000 patient years for the combined end point were 18 (SU), 10 (DPP‐4 inhibitor), 8 (GLP‐1 agonist) and 21 (insulin). In adjusted analyses with metformin + SU as reference, metformin + DPP‐4 inhibitor was associated with an RR of 0.65 (0.54–0.80) for mortality, an RR of 0.57 (0.40–0.80) for CV mortality and an RR of 0.70 (0.57–0.85) for the combined end point. For metformin + GLP‐1 agonist, the RR for mortality was 0.77 (0.51–1.17), for CV mortality 0.89 (0.47–1.68), and for the combined end point 0.82 (0.55–1.21).ConclusionIncretin‐based drugs combined with metformin were safe compared with conventional combinations of glucose‐lowering therapy. Use of incretin‐based therapy may be target for strategies to lower CV risk in type 2 diabetes, although it should be recognized that the multivariable analysis may not have fully accounted for important baseline differences.
Towards the identification of a genetic basis for Landau‐Kleffner syndrome
Authors: Conroy Judith , McGettigan Paul A. , McCreary Dara , Shah Naisha , Collins Kevin , Parry‐Fielder Bronwyn , Moran Margaret , Hanrahan Donncha , Deonna Thierry W. , Korff Christian M. , Webb David , Ennis Sean , Lynch Sally A. , King Mary D. 
Published: May 2014

SummaryObjectiveTo establish the genetic basis of Landau‐Kleffner syndrome (LKS) in a cohort of two discordant monozygotic (MZ) twin pairs and 11 isolated cases.MethodsWe used a multifaceted approach to identify genetic risk factors for LKS. Array comparative genomic hybridization (CGH) was performed using the Agilent 180K array. Whole genome methylation profiling was undertaken in the two discordant twin pairs, three isolated LKS cases, and 12 control samples using the Illumina 27K array. Exome sequencing was undertaken in 13 patients with LKS including two sets of discordant MZ twins. Data were analyzed with respect to novel and rare variants, overlapping genes, variants in reported epilepsy genes, and pathway enrichment.ResultsA variant (cG1553A) was found in a single patient in the GRIN2A gene, causing an arginine to histidine change at site 518, a predicted glutamate binding site. Following copy number variation (CNV), methylation, and exome sequencing analysis, no single candidate gene was identified to cause LKS in the remaining cohort. However, a number of interesting additional candidate variants were identified including variants in RELN, BSN, EPHB2, and NID2.SignificanceA single mutation was identified in the GRIN2A gene. This study has identified a number of additional candidate genes including RELN, BSN, EPHB2, and NID2.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Human dermal fibroblast migration induced by fibronectin in autocrine and paracrine manners
Authors: Li Xiaoguang , Qian Hua , Ono Fumitake , Tsuchisaka Atsunari , Krol Rafal P. , Ohara Koji , Hayakawa Taihei , Matsueda Satoko , Sasada Tetsuro , Ohata Chika , Furumura Minao , Hamada Takahiro , Hashimoto Takashi 
Published: May 2014

AbstractAlthough fibronectin (FN) is known as a chemoattractant for human dermal fibroblasts (HDFs), it is unclear whether HDF migration is stimulated by FN produced by HDFs (autocrine manner) or by keratinocytes (paracrine manner). In this study, we investigated HDF migration by Boyden chamber assay using conditioned media from HDFs and HaCaT cells (keratinocyte cell line). Immunoblotting and enzyme‐linked immunosorbent assay revealed that FN existed in both conditioned media. Boyden chamber assay showed both conditioned media stimulated HDF migration, which was inhibited by anti‐FN antibody. Antibodies to both integrin β1and β3 subunits inhibited HDF migration induced by HDF‐conditioned medium almost completely and that by HaCaT cell‐conditioned medium with 50–60%. These results suggested that HDF migration was stimulated by FN in both autocrine and paracrine manners. However, the mechanisms of HDF migration by FN, particularly the role of integrin β1 and β3 subunits, were slightly different between autocrine and paracrine manners.
HAUSP, a novel deubiquitinase for Rb – MDM2 the critical regulator
Authors: Bhattacharya Seemana , Ghosh Mrinal K. 
Published: May 2014

Tumor suppressor retinoblastoma‐associated protein (Rb) is an important cell cycle regulator, arresting cells in early G1. It is commonly inactivated in cancers and its level is maintained during the cell cycle. Rb is regulated by various post‐translational modifications such as phosphorylation, acetylation, ubiquitination and so on. Several E3 ligases including murine double minute 2 (MDM2) promote the degradation of Rb. This study focuses on the role of HAUSP (herpes virus associated ubiquitin specific protease) on Rb. Here, we show that HAUSP colocalizes and interacts with Rb to stabilize it from proteasomal degradation by removing wild‐type and K48‐linked ubiquitin chains in human embryonic kidney 293 (HEK293) cells. HAUSP deubiquitinates Rb in vivo and in vitro, leading to an increased cell population in the G1 phase. Hence, HAUSP is a novel deubiquitinase for Rb. Immunohistochemistry, western blotting and cell‐based assays show that HAUSP is overexpressed in glioma and contributes towards glioma progression. However, HAUSP activity on Rb is abrogated in glioma (cancer), where these two proteins show an inverse relationship. MDM2 (a known substrate of HAUSP) serves as a better target for HAUSP‐mediated deubiquitination in cancer cells, facilitating degradation of Rb and oncogenic progression. This novel regulatory axis is proteasome mediated, p53 independent, and the level of MDM2 is critical. The shift in equilibrium by differential deubiquitination in regulation of Rb explains a subtle difference existing between normal and cancer cells. This leads to speculation about a new possibility for distinguishing cancer cells from normal cells at the molecular level, which may be investigated for therapeutic intervention in the future.Structured digital abstract

HAUSP and Rb colocalize by fluorescence microscopy (View interaction)
HAUSP binds to Rb by pull down (View interaction)
HAUSP physically interacts with Rb by anti bait coip (1, 2, 3, 4, 5, 6)
3‐D analysis of bacterial cell‐(iron)mineral aggregates formed during Fe(II) oxidation by the nitrate‐reducing Acidovorax sp. strain BoFeN1 using complementary microscopy tomography approaches
Authors: Schmid G. , Zeitvogel F. , Hao L. , Ingino P. , Floetenmeyer M. , Stierhof Y.‐D. , Schroeppel B. , Burkhardt C. J. , Kappler A. , Obst M. 
Published: May 2014

AbstractThe formation of cell‐(iron)mineral aggregates as a consequence of bacterial iron oxidation is an environmentally widespread process with a number of implications for processes such as sorption and coprecipitation of contaminants and nutrients. Whereas the overall appearance of such aggregates is easily accessible using 2‐D microscopy techniques, the 3‐D and internal structure remain obscure. In this study, we examined the 3‐D structure of cell‐(iron)mineral aggregates formed during Fe(II) oxidation by the nitrate‐reducing Acidovorax sp. strain BoFeN1 using a combination of advanced 3‐D microscopy techniques. We obtained 3‐D structural and chemical information on different cellular encrustation patterns at high spatial resolution (4–200 nm, depending on the method): more specifically, (1) cells free of iron minerals, (2) periplasm filled with iron minerals, (3) spike‐ or platelet‐shaped iron mineral structures, (4) bulky structures on the cell surface, (5) extracellular iron mineral shell structures, (6) cells with iron mineral filled cytoplasm, and (7) agglomerations of extracellular globular structures. In addition to structural information, chemical nanotomography suggests a dominant role of extracellular polymeric substances (EPS) in controlling the formation of cell‐(iron)mineral aggregates. Furthermore, samples in their hydrated state showed cell‐(iron)mineral aggregates in pristine conditions free of preparation (i.e., drying/dehydration) artifacts. All these results were obtained using 3‐D microscopy techniques such as focused ion beam (FIB)/scanning electron microscopy (SEM) tomography, transmission electron microscopy (TEM) tomography, scanning transmission (soft) X‐ray microscopy (STXM) tomography, and confocal laser scanning microscopy (CLSM). It turned out that, due to the various different contrast mechanisms of the individual approaches, and due to the required sample preparation steps, only the combination of these techniques was able to provide a comprehensive understanding of structure and composition of the various Fe‐precipitates and their association with bacterial cells and EPS.
Differential SALL4 immunoexpression in malignant rhabdoid tumours and epithelioid sarcomas
Authors: Yoshida Akihiko , Asano Naofumi , Kawai Akira , Kawamoto Hiroshi , Nakazawa Atsuko , Kishimoto Hiroshi , Kushima Ryoji 
Published: May 2014

AimsMalignant rhabdoid tumours (MRTs) and epithelioid sarcomas (ESs) are distinctive malignant neoplasms with characteristic clinicopathological features. However, these two tumour types share some phenotypic features, such as epithelioid/rhabdoid cytology, expression of epithelial markers, and immunohistochemical loss of INI1. The distinction can be problematic in atypical clinical settings, and ancillary diagnostic tools are needed. The expression of CD34 is widely cited as favouring the diagnosis of ES, but no formal comparative study has been performed in the post‐INI1 era. Here, we evaluated the utility of SALL4 for differentiating MRTs from ESs, and compared its performance with that of CD34.Methods and resultsFifteen MRTs and 36 ESs were retrieved. All MRTs and ESs lacked INI1 reactivity, except for one MRT that lacked BRG1. A representative slide from each case was stained using antibodies against SALL4 and CD34. Ten (67%) of the 15 MRTs expressed SALL4. In contrast, only one (3%) of the 36 ESs expressed SALL4. CD34 staining was observed in nine (60%) of the MRTs and 29 (81%) of the ESs.ConclusionsDespite moderate sensitivity, SALL4 expression may aid in distinguishing MRTs from ESs. CD34 was found to have questionable utility in making such distinctions.