bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Common and Rare Genetic Variation Associated With Plasma Protein Levels Using Whole-Exome Sequencing and Mass Spectrometry
Authors: Solomon Terry , Lapek John D. , Jensen Søren Beck , Greenwald William W. , Hindberg Kristian , Matsui Hiroko , Latysheva Nadezhda , Braekken Sigrid K. , Gonzalez David J. , Frazer Kelly A. , Smith Erin N. , Hansen John-Bjarne 
Published: December 2018

Background:
Identifying genetic variation associated with plasma protein levels, and the mechanisms by which they act, could provide insight into alterable processes involved in regulation of protein levels. Although protein levels can be affected by genetic variants, their estimation can also be biased by missense variants in coding exons causing technical artifacts. Integrating genome sequence genotype data with mass spectrometry-based protein level estimation could reduce bias, thereby improving detection of variation that affects RNA or protein metabolism.

Methods:
Here, we integrate the blood plasma protein levels of 664 proteins from 165 participants of the Tromsø Study, measured via tandem mass tag mass spectrometry, with whole-exome sequencing data to identify common and rare genetic variation associated with peptide and protein levels (protein quantitative trait loci [pQTLs]). We additionally use literature and database searches to prioritize putative functional variants for each pQTL.

Results:
We identify 109 independent associations (36 protein and 73 peptide) and use genotype data to exclude 49 (4 protein and 45 peptide) as technical artifacts. We describe 2 particular cases of rare variation: 1 associated with the complement pathway and 1 with platelet degranulation. We identify putative functional variants and show that pQTLs act through diverse molecular mechanisms that affect both RNA and protein metabolism.

Conclusions:
We show that although the majority of pQTLs exert their effects by modulating RNA metabolism, many affect protein levels directly. Our work demonstrates the extent by which pQTL studies are affected by technical artifacts and highlights how prioritizing the functional variant in pQTL studies can lead to insights into the molecular steps by which a protein may be regulated.
Society of Thoracic Surgeons Risk Score and EuroSCORE-2 Appropriately Assess 30-Day Postoperative Mortality in the STICH Trial and a Contemporary Cohort of Patients With Left Ventricular Dysfunction Undergoing Surgical Revascularization
Authors: Bouabdallaoui Nadia , Stevens Susanna R. , Doenst Torsten , Petrie Mark C. , Al-Attar Nawwar , Ali Imtiaz S. , Ambrosy Andrew P. , Barton Anna K. , Cartier Raymond , Cherniavsky Alexander , Demondion Pierre , Desvigne-Nickens Patrice , Favaloro Robert R. , Gradinac Sinisa , Heinisch Petra , Jain Anil , Jasinski Marek , Jouan Jerome , Kalil Renato A.K. , Menicanti Lorenzo , Michler Robert E. , Rao Vivek , Smith Peter K. , Zembala Marian , Velazquez Eric J. , Al-Khalidi Hussein R. , Rouleau Jean L. ,   for the STICH Trial Investigators
Published: December 2018

Background:
The STICH trial (Surgical Treatment for Ischemic Heart Failure) demonstrated a survival benefit of coronary artery bypass grafting in patients with ischemic cardiomyopathy and left ventricular dysfunction. The Society of Thoracic Surgeons (STS) risk score and the EuroSCORE-2 (ES2) are used for risk assessment in cardiac surgery, with little information available about their accuracy in patients with left ventricular dysfunction. We assessed the ability of the STS score and ES2 to evaluate 30-day postoperative mortality risk in STICH and a contemporary cohort (CC) of patients with a left ventricle ejection fraction ≤35% undergoing coronary artery bypass grafting outside of a trial setting.

Methods and Results:
The STS and ES2 scores were calculated for 814 STICH patients and 1246 consecutive patients in a CC. There were marked variations in 30-day postoperative mortality risk from 1 patient to another. The STS scores consistently calculated lower risk scores than ES2 (1.5 versus 2.9 for the CC and 0.9 versus 2.4 for the STICH cohort), and underestimated postoperative mortality risk. The STS and ES2 scores had moderately good C statistics: CC (0.727, 95% CI: 0.650–0.803 for STS, and 0.707, 95% CI: 0.620–0.795 for ES2); STICH (0.744, 95% CI: 0.677–0.812, for STS and 0.736, 95% CI: 0.665–0.808 for ES2). Despite the CC patients having higher STS and ES2 scores than STICH patients, mortality (3.5%) was lower than that of STICH (4.8%), suggesting a possible decrease in postoperative mortality over the past decade.

Conclusions:
The 30-day postoperative mortality risk of coronary artery bypass grafting in patients with left ventricular dysfunction varies markedly. Both the STS and ES2 score are effective in evaluating risk, although the STS score tend to underestimate risk.

CLINICAL TRIAL REGISTRATION:

URL:
https://www.clinicaltrials.gov.
Unique identifier: NCT00023595.
Association Between Regional Adipose Tissue Distribution and Risk of Heart Failure Among Blacks
Authors: Pandey Ambarish , Kondamudi Nitin , Patel Kershaw V. , Ayers Colby , Simek Shawn , Hall Michael E. , Musani Solomon K. , Blackshear Chad , Mentz Robert J. , Khan Hassan , Terry James G. , Correa Adolfo , Butler Javed , Neeland Ian J. , Berry Jarett D. 
Published: December 2018

Background:
Obesity is highly prevalent among blacks and is associated with a greater risk of heart failure (HF). However, the contribution of regional adiposity depots such as visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue toward risk of HF in blacks is unknown.

Methods and Results:

We included 2602 participants (mean age: 59 years, 35% men) from the Jackson Heart Study without prevalent HF who underwent computed tomography quantification of VAT and subcutaneous adipose tissue during the second visit (2005–2009). The associations between different adiposity measures and HF were evaluated using adjusted Cox models. There were 122 incident HF events over a median follow-up of 7.1 years. Higher amounts of VAT were associated with greater risk of HF in age- and sex-adjusted analyses (hazard ratio [95% CI] per 1-SD higher VAT: 1.29 [1.09–1.52]). This association was attenuated and not significant after additional adjustment for traditional HF risk factors and body mass index. Overall obesity, represented by body mass index, was associated with higher risk of HF independent of risk factors and VAT (hazard ratio [95% CI] per 1-kg/m
2
higher body mass index: 1.06 [1.02–1.11]). Subcutaneous adipose tissue was not associated with risk of HF in adjusted analyses.

Conclusions:
In a community-dwelling black population, higher amounts of overall and visceral adiposity are associated with higher risk of HF. The association between VAT and HF risk in blacks may reflect differences in traditional HF risk factor burden. Future studies are needed to confirm this observation and clarify the independent role of different measures of adiposity on HF outcomes.
Drug-Coated Balloon Angioplasty for Femoropopliteal In-Stent Restenosis
Authors: Cassese Salvatore , Wolf Florian , Ingwersen Maja , Kinstner Christian M. , Fusaro Michele , Ndrepepa Gjin , Ibrahim Tareq , Ott Ilka , Lammer Johannes , Krankenberg Hans , Fusaro Massimiliano 
Published: December 2018

Background:
The optimal revascularization therapy for in-stent restenosis (ISR) of femoropopliteal arteries represents a matter of debate. We investigated the outcomes of patients treated with drug-coated balloon (DCB) angioplasty for ISR of femoropopliteal arteries.

Methods and Results:

Patient-level data from 3 randomized trials of DCB angioplasty for ISR of femoropopliteal arteries were pooled. The primary outcome was target lesion revascularization. The main secondary outcome was recurrent ISR. Other outcomes of interest were ipsilateral amputation, death, Rutherford class improvement, and ankle-brachial index at follow-up. A total of 263 patients randomly assigned to DCB (n=133) or plain balloon angioplasty (n=130) were included in the analysis. After a follow-up of 12 months, patients treated with DCB angioplasty displayed a lower risk for target lesion revascularization (hazard ratio [95% CIs]: 0.25 [0.14–0.46];
P
<0.001) and recurrent ISR (0.19 [0.10–0.35];
P
<0.001) as compared with those treated with plain balloon angioplasty. There was no significant interaction between the treatment effect for target lesion revascularization and high-risk subgroups of patients such as those with diabetes mellitus, longer lesions, small vessels, moderate to severe underlying calcification, and occlusive pattern of ISR. DCB and plain balloon angioplasty were comparable with respect to other secondary outcomes.

Conclusions:
In case of femoropopliteal ISR, the percutaneous treatment with DCB angioplasty is associated with superior clinical and antirestenotic efficacy as compared with plain balloon angioplasty at 1-year follow-up, without attrition of efficacy in high-risk subgroups of patients. The long-term durability of DCB angioplasty in this setting remains to be further investigated.
Imagos of Camelobaetidius francischettii Salles, Andrade &amp; Da-Silva (Ephemeroptera: Baetidae)
Authors: BOLDRINI RAFAEL , SALLES FREDERICO FALCÃO , PES ANA MARIA OLIVEIRA 
Published: December 2018

The genus Camelobaetidius Demoulin (Ephemeroptera: Baetidae) is represented in South America by 28 species: 20 of them are described based on nymphs, three based solely on adults, and five based on nymphs and adults (Dominguez et al., 2006; Boldrini & Salles, 2009; Salles & Nascimento, 2009). As mentioned by Boldrini & Salles (2009), the species of the genus can be divided into three morphological groups: a) those species with the terminal filament reduced and with a projection on the inner margin of the fore femora; b) species with the terminal filament reduced and without a projection on the inner margin of the fore femora; and c) species with the terminal filament almost as long as cerci. Of these five species described based on nymphs and adults, nymphs of four of them present the terminal filament well developed, whereas in only one, C. billi Thomas & Dominique, nymphs present the terminal filament reduced (Dominguez et al., 2006). Importantly, adults of Camelobaetidius whose nymphs present the terminal filament reduced and a projection on the inner margin of the fore femora, as C. leentvaari Demoulin, the type-species, remain unknown.
Novel Therapeutic Strategy for Pharyngoesophageal Stricture following Total Laryngectomy
Authors: Wu Peter I. , Szczesniak Michal M. , Fox Dart A. , Maclean Julia , Blom Eric D. , Cook Ian J. 
Published: December 2018

Current therapeutic strategies for pharyngoesophageal stricture, while effective in the short term, are protracted and costly in the longer term. Conceptually, if a stricture can be dilated with minimal tissue injuries, the rate of fibrosis and the resultant stricture recurrence could be reduced. We evaluated a prototype computer‐controlled syringe pump device programmed to distend a commercially available balloon dilator at variable rate, asserting incremental lumen distension pressures tailored to the resistive force encountered within the stricture. We completed 17 graded dilatation procedures among 4 total laryngectomy patients. All patients had a short‐term response (1 month), with a mean decrement (improvement) in Sydney Swallow Questionnaire score of 448 (total score range, 0‐1700; normal <234). The overall procedural tolerability and safety were encouraging; the only complication was the displacement of the voice prosthesis during 1 dilatation. From a technical viewpoint, the main challenge was to maintain the balloon in position during dilatation.
Salvage Surgery for Recurrence after Radiotherapy for Squamous Cell Carcinoma of the Head and Neck
Authors: Elbers Joris B. W. , Al‐Mamgani Abrahim , van den Brekel Michiel W. M. , Jóźwiak Katarzyna , de Boer J. P. , Lohuis Peter J. F. M. , Willems Stefan M. , Verheij Marcel , Zuur Charlotte L. 
Published: December 2018

ObjectiveMost studies that report on salvage surgery after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) are small and heterogeneous. Subsequently, some relevant questions remain unanswered. We specifically focused on (1) difference in prognosis per tumor subsite, corrected for disease stage, and (2) differences in prognosis after salvage surgery for local, regional, and locoregional recurrences.Study DesignRetrospective analysis.SettingSingle‐center study (2000‐2016).Subjects and MethodsPatients treated with salvage surgery for HNSCC recurrence after (chemo)radiotherapy.ResultsIn total, 189 patients were included. Five‐year overall survival (OS) was 33%, and median OS was 18 (95% confidence interval [CI], 11‐26) months. Treatment‐related mortality was 2%. Larynx carcinoma was associated with more favorable local (adjusted hazard ratio [HR] = 4.02; 95% CI, 1.46‐11.10; P =. 007) and locoregional control (adjusted HR = 5.34; 95% CI, 1.83‐15.61; P =. 002) than pharyngeal carcinoma. American Society of Anesthesiologists (ASA) score (≥3 vs 1‐2: adjusted HR = 3.04; 95% CI, 1.17‐7.91; P =. 023), pT stage (3‐4 vs 1‐2: adjusted HR = 4.41; 95% CI, 1.65‐11.82; P =. 003), and salvage surgery for locoregional recurrences (locoregional vs local: adjusted HR = 3.81; 95% CI, 1.13‐11.82; P =. 021) were independent predictors for disease‐free survival (DFS).ConclusionSalvage surgery for larynx carcinoma, regardless of disease stage and other prognostic factors, results in more favorable loco(regional) control but not favorable DFS than pharyngeal carcinoma. The observed difference in DFS between salvage surgery for local and regional recurrences was not significant after correction for confounders. However, survival following salvage surgery for locoregional disease is significantly worse. For this subgroup, we propose to consider T status and comorbidity for clinical decision making, as high pT stage and ASA score are independent predictors for worse DFS.
Retinal degeneration is associated with brain volume reduction and prognosis in radiologically isolated syndrome
Authors: Vural Atay , Okar Serhat , Kurne Aslı , Sayat-Gürel Güliz , Acar Nazire Pınar , Karabulut Erdem , Oğuz Kader Karlı , Kadayıfçılar Sibel , Karabudak Rana 
Published: December 2018

Background: The extent of neurodegeneration in the earliest stages of central nervous system (CNS) demyelination is not known. Optical coherence tomography (OCT) is a powerful tool to study neurodegeneration in demyelinating disorders. Objectives: To study neuroaxonal loss in the retina of individuals with radiologically isolated syndrome (RIS) and investigate whether OCT measurements are associated with brain volumetrics and clinical conversion to multiple sclerosis (MS). Methods: Subjects fulfilling the Okuda criteria for RIS ( n = 15 patients, 30 eyes) and age- and sex-matched healthy controls (HC) underwent spectral-domain OCT and magnetic resonance imaging for volumetric measurement of brain structures. Results: Macular ganglion cell-inner plexiform layer (mGCIPL), macular retinal nerve fiber layer (mRNFL), and temporal peripapillary RNFL (pRNFL) thickness; normalized total brain volume (nTBV); and normalized thalamic volume (nTV) were reduced in RIS compared to HC. mGCIPL, mRNFL, and pRNFL measurements were associated with nTBV, nTV, and normalized gray and white matter volumes in the RIS group. pRNFL was thinner in individuals with RIS who converted to MS in 5 years. Conclusions: Retinal neurodegeneration can be detected in the papillomacular region in the earliest stages of CNS demyelination and reflects global disease processes in the brain. OCT can be potentially useful for predicting prognosis in RIS.
‘Robosurgeons vs. robosceptics’: can we afford robotic technology or can we afford not to?
Authors: Sandhu Jasmesh 
Published: December 2018

Aim: To investigate the clinical effectiveness and cost-effectiveness of robotic technology in robotic-assisted radical prostatectomy in comparison with laparoscopic radical prostatectomy and open radical prostatectomy. Methods: Cochrane, Medline and Embase databases were searched for randomised controlled trials to date on robotic-assisted radical prostatectomy versus laparoscopic radical prostatectomy and robotic-assisted radical prostatectomy versus open radical prostatectomy to assess clinical effectiveness. The British Association of Urology Surgeons database (2014–2016) and Cancer Research UK (2012–2014) were accessed in conjunction with media; keywords included: ‘Da Vinci’, ‘first robotic prostatectomy’, ‘hospital’ to estimate the cost-effectiveness of robotic-assisted radical prostatectomy in the National Health Service. Results: Functional outcome rates improved with robotic-assisted radical prostatectomy; this benefits the National Health Service financially although the clinical effectiveness may not meet the threshold of clinical importance. Regarding cost-effectiveness, approximately 12/43 (27.9%) centres achieved 150 robotic-assisted radical prostatectomies per year while 26/43 (60.4%) centres have managed to meet 100 robotic-assisted radical prostatectomies per year in 2014–2016. A national mean of 120–130 robotic-assisted radical prostatectomies per year for 2014–2016 was estimated. Conclusion: The cost of robotic-assisted radical prostatectomy is adequately justified if a high volume of surgeries (>150) are performed in high volume centres by high volume experienced surgeons per year. This can be achieved by subsidising the cost of robotic technology, centralisation and establishing robotic training centres.
Single-cell analyses demonstrate that a heme–GATA1 feedback loop regulates red cell differentiation
Authors: Doty Raymond T. , Yan Xiaowei , Lausted Christopher , Munday Adam D. , Yang Zhantao , Yi Danielle , Jabbari Neda , Liu Li , Keel Siobán B. , Tian Qiang , Abkowitz Janis L. 
Published: December 2018

AbstractErythropoiesis is the complex, dynamic, and tightly regulated process that generates all mature red blood cells. To understand this process, we mapped the developmental trajectories of progenitors from wild-type, erythropoietin-treated, and Flvcr1-deleted mice at single-cell resolution. Importantly, we linked the quantity of each cell’s surface proteins to its total transcriptome, which is a novel method. Deletion of Flvcr1 results in high levels of intracellular heme, allowing us to identify heme-regulated circuitry. Our studies demonstrate that in early erythroid cells (CD71+Ter119neg-lo), heme increases ribosomal protein transcripts, suggesting that heme, in addition to upregulating globin transcription and translation, guarantees ample ribosomes for globin synthesis. In later erythroid cells (CD71+Ter119lo-hi), heme decreases GATA1, GATA1-target gene, and mitotic spindle gene expression. These changes occur quickly. For example, in confirmatory studies using human marrow erythroid cells, ribosomal protein transcripts and proteins increase, and GATA1 transcript and protein decrease, within 15 to 30 minutes of amplifying endogenous heme synthesis with aminolevulinic acid. Because GATA1 initiates heme synthesis, GATA1 and heme together direct red cell maturation, and heme stops GATA1 synthesis, our observations reveal a GATA1–heme autoregulatory loop and implicate GATA1 and heme as the comaster regulators of the normal erythroid differentiation program. In addition, as excessive heme could amplify ribosomal protein imbalance, prematurely lower GATA1, and impede mitosis, these data may help explain the ineffective (early termination of) erythropoiesis in Diamond Blackfan anemia and del(5q) myelodysplasia, disorders with excessive heme in colony-forming unit-erythroid/proerythroblasts, explain why these anemias are macrocytic, and show why children with GATA1 mutations have DBA-like clinical phenotypes.
Factors Related to Advanced Stage of Cancer Presentation in Botswana
Authors: Anakwenze Chidinma , Bhatia Rohini , Rate William , Bakwenabatsile Lame , Ngoni Kebatshabile , Rayne Sarah , Dhillon Preet , Narasimhamurthy Mohan , Ho-Foster Ari , Ramogola-Masire Doreen , Grover Surbhi 
Published: December 2018

Purpose Botswana, a country with a high prevalence of HIV, has an increasing incidence of cancer-related mortality in the post–antiretroviral therapy era. Despite universal access to free health care, the majority of Botswana patients with cancer present at advanced stages. This study was designed to explore the factors related to advanced-stage cancer presentation in Botswana. Methods Patients attending an oncology clinic between December 2015 and January 2017 at Princess Marina Hospital in Gaborone, Botswana, completed a questionnaire on sociodemographic and clinical factors as well as cancer-related fears, attitudes, beliefs, and stigma. Odds ratios (ORs) were calculated to identify factors significantly associated with advanced stage (stage III and IV) at diagnosis. Results Of 214 patients, 18.7% were men and 81.3% were women. The median age at diagnosis was 46 years, with 71.9% of patients older than 40 years. The most commonly represented cancers included cervical (42.3%), breast (16%), and head and neck (15.5%). Cancer stages represented in the study group included 8.4% at stage I, 19.2% at stage II, 24.1% at stage III, 11.9% at stage IV, and 36.4% at an unknown stage. Patients who presented at advanced stages were significantly more likely to not be afraid of having cancer (OR, 3.48; P < .05), believe that their family would not care for them if they needed treatment (OR, 6.35; P = .05), and believe that they could not afford to develop cancer (OR, 2.73; P < .05). The perception that symptoms were less serious was also significantly related to advanced stage ( P < .05). Patients with non–female-specific cancers were more likely to present in advanced stages (OR, 5.67; P < .05). Conclusion Future cancer mortality reduction efforts should emphasize cancer symptom awareness and early detection through routine cancer screening, as well as increasing the acceptability of care-seeking, especially among male patients.