bluuebunny/crossref_metadata_2025_split huggingface dataset:
Core Transcription Factors, MicroRNAs, and Small Molecules Drive Transdifferentiation of Human Fibroblasts Towards The Cardiac Cell Lineage
Authors: Christoforou Nicolas , Chakraborty Syandan , Kirkton Robert D. , Adler Andrew F. , Addis Russell C. , Leong Kam W. 
Published: January 2017

AbstractTransdifferentiation has been described as a novel method for converting human fibroblasts into induced cardiomyocyte-like cells. Such an approach can produce differentiated cells to study physiology or pathophysiology, examine drug interactions or toxicities, and engineer cardiac tissues. Here we describe the transdifferentiation of human dermal fibroblasts towards the cardiac cell lineage via the induced expression of transcription factors GATA4, TBX5, MEF2C, MYOCD, NKX2–5, and delivery of microRNAs miR-1 and miR-133a. Cells undergoing transdifferentiation expressed ACTN2 and TNNT2 and partially organized their cytoskeleton in a cross-striated manner. The conversion process was associated with significant upregulation of a cohort of cardiac-specific genes, activation of pathways associated with muscle contraction and physiology, and downregulation of fibroblastic markers. We used a genetically encoded calcium indicator and readily detected active calcium transients although no spontaneous contractions were observed in transdifferentiated cells. Finally, we determined that inhibition of Janus kinase 1, inhibition of Glycogen synthase kinase 3, or addition of NRG1 significantly enhanced the efficiency of transdifferentiation. Overall, we describe a method for achieving transdifferentiation of human dermal fibroblasts into induced cardiomyocyte-like cells via transcription factor overexpression, microRNA delivery, and molecular pathway manipulation.
Prevalence of feral swine disturbance at important archaeological sites over a large landscape in Florida
Authors: Engeman Richard M. , Meyer Joseph S. , Allen John B. 
Published: January 2017

AbstractFeral swine are globally known as one of the most destructive invasive vertebrates, damaging native habitats, native plants and animals, agriculture, infrastructure, spreading diseases. There has been little quantification on their disturbance to archaeological sites across a broad landscape. Over 6 years we inspected 293 significant archaeological sites for swine disturbance across a vast area. We found a 42% prevalence of swine disturbance among all sites, with prevalence not distinguishable among prehistoric sites, historic sites, and sites with both components. The areas of disturbance mapped within three historic homestead sites showed 5–26% of total site surface area rooted. Disturbance was not evident upon re-inspection of one of these sites after 18 months, indicating how evidence of disturbance can be obscured in this environment. Thus, our observed 42% prevalence of disturbance should be considered a minimum for disturbance occurring through time. Artifacts depths were <10 cm of the surface at 85% of the sites and <20 cm of the surface for 90% of the sites. Feral swine rooting commonly exceeds 20 cm in depth, especially in soft sandy substrates typical of Florida, making the great majority of the studied sites highly vulnerable to artifact damage or displacement.
Sox10+ adult stem cells contribute to biomaterial encapsulation and microvascularization
Authors: Wang Dong , Wang Aijun , Wu Fan , Qiu Xuefeng , Li Ye , Chu Julia , Huang Wen-Chin , Xu Kang , Gong Xiaohua , Li Song 
Published: January 2017

AbstractImplanted biomaterials and biomedical devices generally induce foreign body reaction and end up with encapsulation by a dense avascular fibrous layer enriched in extracellular matrix. Fibroblasts/myofibroblasts are thought to be the major cell type involved in encapsulation, but it is unclear whether and how stem cells contribute to this process. Here we show, for the first time, that Sox10+ adult stem cells contribute to both encapsulation and microvessel formation. Sox10+ adult stem cells were found sparsely in the stroma of subcutaneous loose connective tissues. Upon subcutaneous biomaterial implantation, Sox10+ stem cells were activated and recruited to the biomaterial scaffold, and differentiated into fibroblasts and then myofibroblasts. This differentiation process from Sox10+ stem cells to myofibroblasts could be recapitulated in vitro. On the other hand, Sox10+ stem cells could differentiate into perivascular cells to stabilize newly formed microvessels. Sox10+ stem cells and endothelial cells in three-dimensional co-culture self-assembled into microvessels, and platelet-derived growth factor had chemotactic effect on Sox10+ stem cells. Transplanted Sox10+ stem cells differentiated into smooth muscle cells to stabilize functional microvessels. These findings demonstrate the critical role of adult stem cells in tissue remodeling and unravel the complexity of stem cell fate determination.
Allergy reduces the risk of meningioma: a meta-analysis
Authors: Wang Peng-fei , Ji Wen-Jun , Zhang Xiao-hui , Li Shou-wei , Yan Chang-Xiang 
Published: January 2017

AbstractMeningiomas are the most common brain tumours; however, little is known regarding their aetiology. The data are inconsistent concerning atopic disease and the risk of developing meningioma. Thus, we conducted a meta-analysis to investigate the association between allergic conditions and the risk of developing meningioma. A systematic literature search was conducted using PubMed and Web of SCI from Jan 1979 to Feb 2016. Two investigators independently selected the relevant articles according to the inclusion criteria. Eight case-control studies and 2 cohort studies were included in the final analysis, comprising 5,679 meningioma cases and 55,621 control subjects. Compared with no history of allergy, the pooled odds ratio (OR) for allergic conditions was 0.81 (0.70–0.94) for meningioma in a random-effects meta-analysis. Inverse correlations of meningioma occurrence were also identified for asthma and eczema, in which the pooled ORs were 0.78 (0.70–0.86) and 0.78 (0.69–0.87), respectively. A reduced risk of meningioma occurrence was identified in hay fever; however, the association was weak (0.88, 95% CI = 0.78–0.99). The source of this heterogeneity could be the various confounding variables in individual studies. Overall, the current meta-analysis indicated that allergy reduced the risk of developing meningiomas. Large cohort studies are required to investigate this relationship.
Reproducibility and Repeatability of Computer Tomography-based Measurement of Abdominal Subcutaneous and Visceral Adipose Tissues
Authors: Lee Yuan-Hao , Hsiao Hsing-Fen , Yang Hou-Ting , Huang Shih-Yi , Chan Wing P. 
Published: January 2017

AbstractExcessive accumulation of abdominal adipose tissue is a widely recognized as a major feature of obesity, and it can be quantified by dual-energy x-ray absorptiometry (DXA). However, in a phantom study, the inter- and intra-instrument reliability of DXA remains unpredictable. Thus, we attempted to determine the precision of estimates from computer tomography-based measurements and analysis with AZE Virtual Place software. To determine the inter-rater reproducibility and intra-rater repeatability of adipose tissue area estimates, we used the automatic boundary-tracing function of the AZE Virtual Place to generate cross-sectional areas of subcutaneous and visceral adipose tissues from the abdomen of reconstructed CT images. The variability of inter-rater and intra-rater estimates expressed as the coefficient of variation ranged from 0.47% to 1.43% for subcutaneous adipose tissue and 1.08% to 2.20% for visceral adipose tissue; the optimal coefficient of variation of the fat rate calculation ranged from 0.55% to 1.13%, respectively. There was high and significant correlation between adipose tissue areas as estimated in 40 obese subjects by two raters or repeatedly on 20 obese subjects by either rater. This indicates excellent reproducibility and repeatability via a computer tomography-based measurement of abdominal subcutaneous and visceral adipose tissues.
Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder
Authors: Charney A W , Ruderfer D M , Stahl E A , Moran J L , Chambert K , Belliveau R A , Forty L , Gordon-Smith K , Di Florio A , Lee P H , Bromet E J , Buckley P F , Escamilla M A , Fanous A H , Fochtmann L J , Lehrer D S , Malaspina D , Marder S R , Morley C P , Nicolini H , Perkins D O , Rakofsky J J , Rapaport M H , Medeiros H , Sobell J L , Green E K , Backlund L , Bergen S E , Juréus A , Schalling M , Lichtenstein P , Roussos P , Knowles J A , Jones I , Jones L A , Hultman C M , Perlis R H , Purcell S M , McCarroll S A , Pato C N , Pato M T , Craddock N , Landén M , Smoller J W , Sklar P 
Published: January 2017

AbstractWe performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10−8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [11C]PBR28 PET study
Authors: Kalk N J , Guo Q , Owen D , Cherian R , Erritzoe D , Gilmour A , Ribeiro A S , McGonigle J , Waldman A , Matthews P , Cavanagh J , McInnes I , Dar K , Gunn R , Rabiner E A , Lingford-Hughes A R 
Published: January 2017

AbstractRepeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [11C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [11C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identifieda prioriwere estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [11C]PBR28VT,in the hippocampus (F(1,24) 5.694;P=0.025), but no difference inVTin other ROIs. Hippocampal [11C]PBR28VTwas positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720,P<0.001), an effect seen in HC alone (r=0.738;P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [11C]PBR28VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.
Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: association to overlapping traits in ADHD and autism
Authors: Naaijen J , Bralten J , Poelmans G ,   The IMAGE consortium, Faraone Stephen , Asherson Philip , Banaschewski Tobias , Buitelaar Jan , Franke Barbara , P Ebstein Richard , Gill Michael , Miranda Ana , D Oades Robert , Roeyers Herbert , Rothenberger Aribert , Sergeant Joseph , Sonuga-Barke Edmund , Anney Richard , Mulas Fernando , Steinhausen Hans-Christoph , Glennon J C , Franke B , Buitelaar J K 
Published: January 2017

AbstractAttention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n=931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms, autism symptom severity and inhibition were performed using principal component regression analyses. Subsequently, gene-wide association analyses were performed. The glutamate gene set showed an association with severity of hyperactivity/impulsivity (P=0.009), which was robust to correcting for genome-wide association levels. The GABA gene set showed nominally significant association with inhibition (P=0.04), but this did not survive correction for multiple comparisons. None of single gene or single variant associations was significant on their own. By analyzing multiple genetic variants within candidate gene sets together, we were able to find genetic associations supporting the involvement of excitatory and inhibitory neurotransmitter systems in ADHD and ASD symptom severity in ADHD.
Ein seltener Fall eines Volvulus des Coecums nach Koloskopie bei Coecum mobile – Darstellung von Diagnostik, operativer Therapie und postoperativen Komplikationen
Authors: Beltzer Christian , Geiger Axel , Schmidt Roland , Danz Burkhardt , Maier Amrei , Karpa Richard , Dikopoulos Nektarios 
Published: January 2017

ZusammenfassungDie Koloskopie ist sowohl als Vorsorgeuntersuchung als auch als therapeutische Endoskopie mit Polypektomie eine sichere Untersuchung. Ernsthafte Komplikationen sind sehr selten. Blutungen oder Nachblutungen können in der Mehrzahl der Fälle durch eine endoskopische Intervention beherrscht werden, wohingegen bei iatrogener Darmperforation zumeist eine operative Therapie erforderlich ist. Weitaus seltenere Komplikationen stellen das Post-Polypektomie-Koagulationssyndrom sowie als Rarität ein Volvulus nach Koloskopie dar. Wir beschreiben den seltenen Fall eines Patienten mit Volvulus des Coecums nach Koloskopie bei vorbestehendem, aber nicht vorbekanntem Coecum mobile. Die spezifischen Befunde der koloskopischen Untersuchung, die klinische, bildgebende und laborchemische Diagnostik sowie die operative Therapie dieser seltenen Krankheitsentität werden dargestellt und diskutiert. Ein Volvulus des Kolons sollte bei abdominalen Schmerzen nach Koloskopie immer als mögliche seltene aber ernsthafte Komplikation differenzialdiagnostisch in Erwägung gezogen werden. Bei Volvulus des Coecums stellt die Hemikolektomie rechts das operative Verfahren der Wahl dar, alternativ ist bei noch vitalem Darm die Coecopexie ohne Resektion möglich.
Climatic regulation of the neurotoxin domoic acid
Authors: McKibben S. Morgaine , Peterson William , Wood A. Michelle , Trainer Vera L. , Hunter Matthew , White Angelicque E. 
Published: January 2017

Significance
We investigate regulation of domoic acid, a potent marine phycotoxin, at the climate scale. Due to the threat domoic acid can pose to public health, marine wildlife, and coastal economies, decades of laboratory experiments have examined controls on domoic acid production without reaching consensus on reliable toxin-producing conditions. Our findings reveal an association between domoic acid in shellfish and climate-scale warm ocean conditions, a unique, large-scale perspective relative to previous work.
Cluster analysis and topoclimate modeling to examine bristlecone pine tree-ring growth signals in the Great Basin, USA
Authors: Tran Tyler J , Bruening Jamis M , Bunn Andrew G , Salzer Matthew W , Weiss Stuart B 
Published: January 2017

Abstract
Tree rings have long been used to make inferences about the environmental factors that influence tree growth. Great Basin bristlecone pine is a long-lived species and valuable dendroclimatic resource, but often with mixed growth signals; in many cases, not all trees at one location are limited by the same environmental variable. Past work has identified an elevational threshold below the upper treeline above which trees are limited by temperature, and below which trees tend to be moisture limited. This study identifies a similar threshold in terms of temperature instead of elevation through fine-scale topoclimatic modeling, which uses a suite of topographic and temperature-sensor data to predict temperatures across landscapes. We sampled trees near the upper limit of growth at four high-elevation locations in the Great Basin region, USA, and used cluster analysis to find dual-signal patterns in radial growth. We observed dual-signal patterns in ring widths at two of those sites, with the signals mimicking temperature and precipitation patterns. Trees in temperature-sensitive clusters grew in colder areas, while moisture-sensitive cluster trees grew in warmer areas. We found thresholds between temperature- and moisture-sensitivity ranging from 7.4°C to 8°C growing season mean temperature. Our findings allow for a better physiological understanding of bristlecone pine growth, and seek to improve the accuracy of climate reconstructions.
Clinical Utility of the Nonstructural 1 Antigen Rapid Diagnostic Test in the Management of Dengue in Returning Travelers With Fever
Authors: Huits Ralph , Soentjens Patrick , Maniewski-Kelner Ula , Theunissen Caroline , Van Den Broucke Steven , Florence Eric , Clerinx Jan , Vlieghe Erika , Jacobs Jan , Cnops Lieselotte , Van Den Bossche Dorien , Van Esbroeck Marjan , Bottieau Emmanuel 
Published: January 2017

AbstractBackgroundRapid diagnostic test (RDT) detecting the nonstructural 1 (NS1) antigen is increasingly used for dengue diagnosis in endemic and nonendemic settings, but its clinical utility has not been studied in travel clinic practice.MethodsFrom August 2012 to July 2016, travelers returning from the tropics with fever were evaluated in the Institute of Tropical Medicine (Antwerp, Belgium) with the routine use of NS1 antigen RDT that provided results within 1 hour. We determined the diagnostic performance, assessed the management of patients with a positive RDT result, and compared it with that of historical cases of dengue diagnosed from 2000 to 2006, when only antibody detection assays were available.ResultsOf 335 travelers evaluated for fever, 54 (16%) were diagnosed with dengue, including 1 severe case. Nonstructural 1 antigen RDT was performed in 308 patients. It was truly positive in 43 of 52 tested dengue cases and falsely positive in only 1 of the 256 nondengue cases; therefore, sensitivity was 82.7% (95% confidence interval [CI], 74.4%–93.0%) and specificity was 99.6% (95% CI, 98.8%–100%). Only 3 (7%) of the 43 febrile travelers “immediately” diagnosed by RDT were admitted, and only 2 (5%) were given empirical antibacterial treatment, without adverse outcome. Admission and antibiotic prescription rates were significantly higher in the historical cases (n = 43) diagnosed by antibody detection (33%, P = .006 and 26%, P = .014, respectively), although the frequency of severe dengue was similar.ConclusionsIn our practice, the diagnostic performance of NS1 antigen RDT substantially contributed in withholding unnecessary hospitalization and antibiotherapy in dengue patients.
In Vivo Correlation of Radiographic Scoring (Radiographic Union Scale for Tibia Fractures) and Biomechanical Data in a Sheep Osteotomy Model: Can We Define Union Radiographically?
Authors: Litrenta Jody , Tornetta Paul , Ricci William , Sanders Roy W. , O'Toole Robert V. , Nascone Jason W. , Faber Henry , Wilson Darren 
Published: January 2017

Objective:
To determine (1) the reliability of the standard and modified Radiographic Union Scale for Tibia fractures (RUST) score in a sheep osteotomy model, and (2) the standard and modified RUST scores that represent biomechanical union.

Design:
The tibia cortices in a sheep osteotomy model treated by intramedullary nails were radiographically evaluated using standard and modified RUST scores. Scores that correlated with biomechanical union, based on the torsional stiffness of the contralateral tibia, were determined.

Intervention:
Two groups of sheep had transverse midshaft osteotomies treated with 10-mm nails after reaming to 11.5 mm. Weight-bearing was allowed as tolerated. Anteroposterior and lateral radiographs were taken at standard intervals from 4 to 12 weeks. The tibial cortices at each time interval were evaluated in a random order by 5 senior orthopaedic trauma surgeons. Each tibia was scored using the standard and modified RUST methods and was assessed for union.

Main Outcome Measures:
The intraclass correlation coefficient (ICC) was determined for standard and modified RUST scores at each time interval and for the assessment of union. The percentages of fractures that were defined as united by the surgeons were tabulated by RUST and modified RUST scores. The torsional stiffness of each tibia was tested at 12 weeks and expressed as a percentage of the contralateral side. We considered biomechanical union to be ≥90% of the torsional stiffness of the normal side.

Results:
The modified RUST score demonstrated consistently higher ICCs than the standard RUST. All reviewers considered a standard RUST of 10 and a modified RUST of 14 to represent radiographic union. The standard RUST was 10.4 (range: 8.6–12) and modified RUST was 14.2 (range: 12.2–16) for tibiae that were biomechanically united.

Conclusions:
The modified RUST score has a slightly higher ICC than the standard RUST. A standard RUST of 10 and a modified RUST of 14 provide an excellent definition of union based on surgeons' opinion and biomechanical testing for a transverse fracture.