bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil Extracellular Traps Promote Angiogenesis
Authors: Aldabbous Lulwah , Abdul-Salam Vahitha , McKinnon Tom , Duluc Lucie , Pepke-Zaba Joanna , Southwood Mark , Ainscough Alexander J. , Hadinnapola Charaka , Wilkins Martin R. , Toshner Mark , Wojciak-Stothard Beata 
Published: July 2016

Objective—
Inflammation and dysregulated angiogenesis are features of endothelial dysfunction in pulmonary hypertension. Neutrophil extracellular traps (NETs), produced by dying neutrophils, contribute to pathogenesis of numerous vascular disorders but their role in pulmonary hypertension has not been studied. We sought evidence of (NETs) formation in pulmonary hypertension and investigated the effect of NETs on endothelial function.

Approach and Results—

Plasma and lung tissues of patients with pulmonary hypertension were analyzed for NET markers. The effects of NETs on endothelial function were studied in vitro and in vivo. Patients with chronic thromboembolic pulmonary hypertension and idiopathic pulmonary hypertension showed elevated plasma levels of DNA, neutrophil elastase, and myeloperoxidase. NET-forming neutrophils and extensive areas of NETosis were found in the occlusive plexiform lesions and vascularized intrapulmonary thrombi. NETs induced nuclear factor κB–dependent endothelial angiogenesis in vitro and increased vascularization of matrigel plugs in vivo. Angiogenic responses were associated with increased release of matrix metalloproteinase-9, heparin-binding epidermal growth factor–like growth factor, latency-associated peptide of the transforming growth factor β1, and urokinase-type plasminogen activator, accompanied by increased endothelial permeability and cell motility. NETs-induced responses depended on myeloperoxidase/H
2
O
2
-dependent activation of Toll-like receptor 4/nuclear factor κB signaling. NETs stimulated the release of endothelin-1 in HPAECs (human pulmonary artery endothelial cells) and stimulated pulmonary smooth muscle cell proliferation in vitro.

Conclusions—
We are the first to implicate NETs in angiogenesis and provide a functional link between NETs and inflammatory angiogenesis in vitro and in vivo. We demonstrate the potential pathological relevance of this in 2 diseases of disordered vascular homeostasis, pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.
Essential Role of Smooth Muscle STIM1 in Hypertension and Cardiovascular Dysfunction
Authors: Kassan Modar , Ait-Aissa Karima , Radwan Eman , Mali Vishal , Haddox Samuel , Gabani Mohanad , Zhang Wei , Belmadani Souad , Irani Kaikobad , Trebak Mohamed , Matrougui Khalid 
Published: July 2016

Objectives—
Chronic hypertension is the most critical risk factor for cardiovascular disease, heart failure, and stroke.

Approach and Results—

Here we show that wild-type mice infused with angiotensin II develop hypertension, cardiac hypertrophy, perivascular fibrosis, and endothelial dysfunction with enhanced stromal interaction molecule 1 (STIM1) expression in heart and vessels. All these pathologies were significantly blunted in mice lacking STIM1 specifically in smooth muscle (Stim1
SMC−/−
). Mechanistically, STIM1 upregulation during angiotensin II–induced hypertension was associated with enhanced endoplasmic reticulum stress, and smooth muscle STIM1 was required for endoplasmic reticulum stress–induced vascular dysfunction through transforming growth factor-β and nicotinamide adenine dinucleotide phosphate oxidase–dependent pathways. Accordingly, knockout mice for the endoplasmic reticulum stress proapoptotic transcriptional factor, CCAAT-enhancer–binding protein homologous protein (CHOP
−/−
), were resistant to hypertension-induced cardiovascular pathologies. Wild-type mice infused with angiotensin II, but not Stim1
SMC−/−
or CHOP
−/−
mice showed elevated vascular nicotinamide adenine dinucleotide phosphate oxidase activity and reduced phosphorylated endothelial nitric oxide synthase, cGMP, and nitrite levels.

Conclusions—
Thus, smooth muscle STIM1 plays a crucial role in the development of hypertension and associated cardiovascular pathologies and represents a promising target for cardiovascular therapy.
Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of
LMOD1, SYNPO2, PDLIM7, PLN
, and
SYNM
Authors: Perisic Matic Ljubica , Rykaczewska Urszula , Razuvaev Anton , Sabater-Lleal Maria , Lengquist Mariette , Miller Clint L. , Ericsson Ida , Röhl Samuel , Kronqvist Malin , Aldi Silvia , Magné Joelle , Paloschi Valentina , Vesterlund Mattias , Li Yuhuang , Jin Hong , Diez Maria Gonzalez , Roy Joy , Baldassarre Damiano , Veglia Fabrizio , Humphries Steve E. , de Faire Ulf , Tremoli Elena ,   on behalf of the IMPROVE Study Group, Odeberg Jacob , Vukojević Vladana , Lehtiö Janne , Maegdefessel Lars , Ehrenborg Ewa , Paulsson-Berne Gabrielle , Hansson Göran K. , Lindeman Jan H.N. , Eriksson Per , Quertermous Thomas , Hamsten Anders , Hedin Ulf 
Published: July 2016

Objective—
Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability.

Approach and Results—

Muscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis.
SYNPO2, SYNM, LMOD1, PDLIM7
, and
PLN
expression positively correlated to typical SMC markers in plaques (Pearson
r
>0.6,
P
<0.0001) and in rat intimal hyperplasia (
r
>0.8,
P
<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitation-sequencing. Functionally, the genes were downregulated by PDGFB (platelet-derived growth factor beta) and IFNg (interferron gamma), exposure to shear flow stress, and oxLDL (oxidized low-density lipoprotein) loading. Genetic variants in
PDLIM7, PLN
, and
SYNPO2
loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL (expression quantitative trait locus), rs11746443 also associated with
PDLIM7
expression in plaques. Mechanistically, silencing of
PDLIM7
in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation.

Conclusions—
We identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation.
Systematic studies of the genus Aegialomys Weksler, Percequillo and Voss, 2006 (Rodentia: Cricetidae: Sigmodontinae): Annotated catalogue of the types of the species-group taxa
Authors: PRADO JOYCE RODRIGUES DO , PERCEQUILLO ALEXANDRE REIS 
Published: July 2016

The genus Aegialomys was described to encompass the former Oryzomys xanthaeolus group, and includes nowadays two species: A. xanthaeolus and A. galapagoensis. Although not very confusing, the taxonomic history of the genus is long, comprising the description of five nominal taxa along the last 180 years: Mus galapagoensis Waterhouse, 1839; Oryzomys bauri Allen, 1892; Oryzomys xanthaeolus Thomas, 1894; Oryzomys baroni Allen, 1897; and Oryzomys xanthaeolus ica Osgood, 1944. Here we gathered and documented all available information about the type material of Aegialomys on which the species names were based, re-described their morphometric and morphological characters, commented their synonyms and taxonomic history, and compiled information about type localities. Additionally, we established a neotype for O. bauri in order to define the nominal taxon objectively.
Convective and Slantwise Trajectory Ascent in Convection-Permitting Simulations of Midlatitude Cyclones
Authors: Rasp Stephan , Selz Tobias , Craig George C. 
Published: July 2016

AbstractAir parcel ascent in midlatitude cyclones driven by latent heat release has been investigated using convection-permitting simulations together with an online trajectory calculation scheme. Three cyclones were simulated to represent different ascent regimes: one continental summer case, which developed strong convection organized along a cold front; one marine winter case representing a slantwise ascending warm conveyor belt; and one autumn case, which contains both ascent types as well as mesoscale convective systems. Distributions of ascent times differ significantly in mean and shape between the convective summertime case and the synoptic wintertime case, with the mean ascent time being one order of magnitude larger for the latter. For the autumn case the distribution is a superposition of both ascent types, which could be separated spatially and temporally in the simulation. In the slowly ascending airstreams a significant portion of the parcels still experienced short phases of convective ascent. These are linked to line convection in the boundary layer for the wintertime case and an elevated conditionally unstable layer in the autumn case. Potential vorticity (PV) modification during ascent has also been investigated. Despite the different ascent characteristics it was found that net PV change between inflow and outflow levels is very close to zero in all cases. The spread of individual PV values, however, is increased after the ascent. This effect is more pronounced for convective trajectories.
Detection and Confirmation of Deafness-Causing Copy Number Variations in the STRC Gene by Massively Parallel Sequencing and Comparative Genomic Hybridization
Authors: Moteki Hideaki , Azaiez Hela , Sloan-Heggen Christina M. , Booth Kevin , Nishio Shin-ya , Wakui Keiko , Yamaguchi Tomomi , Kolbe Diana L. , Iwasa Yoh-ichiro , Shearer A. Eliot , Fukushima Yoshimitsu , Smith Richard J.H. , Usami Shin-ichi 
Published: July 2016

Objective: Copy number variations (CNVs), a major cause of genetic hearing loss, most frequently involve the STRC gene, located on chr15q15.3 and causally related to autosomal recessive non-syndromic hearing loss (ARNSHL) at the DFNB16 locus. The interpretation of STRC sequence data can be challenging due to the existence of a virtually identical pseudogene, pSTRC, that promotes complex genomic rearrangements in this genomic region. Targeted genomic enrichment with massively parallel sequencing (TGE+MPS) has emerged as the preferred method by which to provide comprehensive genetic testing for hearing loss. We aimed to identify CNVs in the STRC region using established and validated bioinformatics methods. Methods: We used TGE+MPS to identify the genetic cause of hearing loss. The CNV results were confirmed with customized array comparative genomic hybridization (array CGH). Results: Three probands with progressive mild to moderate hearing loss were found among 40 subjects with ARNSHL to segregate homozygous STRC deletions and gene to pseudogene conversion. Array CGH showed that the deletions/conversions span multiple genes outside of the exons captured by TGE+MPS. Conclusion: These data further validate the necessity to integrate the detection of both simple variant changes and complex genomic rearrangements in the clinical diagnosis of genetic hearing loss.
Using Respondent-Driven Sampling to Recruit Illegal Drug Purchasers to Evaluate a Drug Market Intervention
Authors: Ober Allison J. , Sussell Jesse , Kilmer Beau , Saunders Jessica , Heckathorn Douglas D. 
Published: July 2016

Background Violent drug markets are not as prominent as they once were in the United States, but they still exist and are associated with significant crime and lower quality of life. The drug market intervention (DMI) is an innovative strategy that uses focused deterrence, community engagement, and incapacitation to reduce crime and disorder associated with these markets. Although studies show that DMI can reduce crime and overt drug activity, one perspective is prominently missing from these evaluations: those who purchase drugs. Objectives This study explores the use of respondent-driven sampling (RDS)—a statistical sampling method—to approximate a representative sample of drug users who purchased drugs in a targeted DMI market to gain insight into the effect of a DMI on market dynamics. Methods Using RDS, we recruited individuals who reported hard drug use (crack or powder cocaine, heroin, methamphetamine, or illicit use of prescriptions opioids) in the last month to participate in a survey. The main survey asked about drug use, drug purchasing, and drug market activity before and after DMI; a secondary survey asked about network characteristics and recruitment. Conclusions Our sample of 212 respondents met key RDS assumptions, suggesting that the characteristics of our weighted sample approximate the characteristics of the drug user network. The weighted estimates for market purchasers are generally valid for inferences about the aggregate population of customers, but a larger sample size is needed to make stronger inferences about the effects of a DMI on drug market activity.
Clonidine and ketamine for stable hemodynamics in off-pump coronary artery bypass
Authors: Patel Jigar , Thosani Rajesh , Kothari Jignesh , Garg Pankaj , Pandya Himani 
Published: July 2016

Background The current era of fast-track extubation and faster recovery after cardiac surgery requires agents that provide perioperative sedation, suppress sympathetic response, reduce opioid requirement, and maintain hemodynamic stability. Methods In a prospective randomized double-blind study, 75 off-pump coronary artery bypass patients were divided into 3 groups of 25 each: group A had clonidine 1 µg·kg–1, group B had clonidine 1 µg·kg–1 and ketamine 1 mg·kg–1, and group C had a saline placebo. Perioperative changes in heart rate, systolic and diastolic blood pressure, sedation score, pain score, and requirement of analgesics, beta blockers, fentanyl, propofol, and inotropes were recorded, as well time to extubation, intensive care unit stay, and 30-day mortality. Results The combination of clonidine and ketamine led to stable hemodynamics and reduced beta-blocker dosage. The sedation score was highest in groups A and B up to 24 h postoperatively. The pain score was lowest in group B in the first 24 h, and the total dose of analgesics was highest in group C. Clonidine and ketamine or clonidine alone reduced extubation time, but intensive care unit stay was unchanged Conclusions Combined low-dose clonidine and ketamine produced perioperative sedation and effective suppression of sympathetic response with stable hemodynamics. Intraoperative beta-blocker use was reduced without increasing inotrope requirement. This combination prolonged the analgesic effect of opioids, reducing postoperative pain score and analgesic requirement. Low-dose clonidine alone produced sedation but did not completely block sympathetic response. Intensive care unit stay and patient outcome were not affected by clonidine or ketamine.
Subcostal closure technique for prevention of postthoracotomy pain syndrome
Authors: Hong Kipyo , Bae Mikyung , Han Sora 
Published: July 2016

Background The purpose of this study was to evaluate the efficacy of our subcostal closure technique in prevention of postthoracotomy pain syndrome. Methods From July 2012 to March 2015, 29 patients in whom a lobectomy was indicated underwent a thoracotomy. The thoracotomy wounds were closed using a subcostal closure technique (subcostal closure group) and outcomes were compared with 31 patients who underwent video-assisted thoracoscopic surgery (thoracoscopy group). The duration of oral opioid consumption was evaluated from medical records, and postoperative pain was evaluated by telephone interview conducted by a trained nurse practitioner who was unaware of the patient’s group. Results Pain scores were higher in the thoracoscopy group compared to the subcostal closure group, reaching statistical significance (Numeric Rating Scale 0.55 ± 0.948 in the subcostal closure group vs. 1.84 ± 1.614 in the thoracoscopy group; p < 0.001, Clinical Pain Scale 0.24 ± 0.435 in the subcostal closure group vs. 0.81 ± 0.703 in the thoracoscopy group; p < 0.001). The number of patients who consumed oral opioids for longer than 2 months after the operation was significantly greater in the thoracoscopy group than the subcostal closure group (6.9% in the subcostal closure group vs. 32.3% in the thoracoscopy group; p = 0.022). Conclusions The subcostal closure technique is useful to prevent postthoracotomy pain syndrome.
Home-based Reach-to-Grasp training for people after stroke is feasible: a pilot randomised controlled trial
Authors: Turton AJ , Cunningham P , van Wijck F , Smartt HJM , Rogers CA , Sackley CM , Jowett S , Wolf SL , Wheatley K , van Vliet P 
Published: July 2016

Objective: To determine feasibility of a randomised controlled trial (RCT) of home-based Reach-to-Grasp training after stroke. Design: single-blind parallel group RCT. Participants: Residual arm deficit less than 12 months post-stroke. Interventions: Reach-to-Grasp training in 14 one-hour therapist’s visits over 6 weeks, plus one hour self-practice per day (total 56 hours). Control: Usual care. Main Measures: Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), pre-randomisation, 7, 12, 24 weeks post-randomisation. Results: Forty-seven participants (Reach-to-Grasp=24, usual care=23) were randomised over 17 months. Reach-to-Grasp participants received a median (IQR) 14 (13,14) visits, and performed 157 (96,211) repetitions per visit; plus 30 minutes (22,45) self-practice per day. Usual care participants received 10.5 (5,14) therapist visits, comprising 38.6 (30,45) minutes of arm therapy with 16 (6,24) repetitions of functional tasks per visit. Median ARAT scores in the reach-to-grasp group were 8.5 (3.0,24.0) at baseline and 14.5 (3.5,26.0) at 24 weeks compared to median of 4 at both time points (IQR: baseline (3.0,14.0), 24 weeks (3.0,30.0)) in the usual-care group. Median WMFT tasks completed at baseline and 24 weeks were 6 (3.0,11.5) and 8.5 (4.5,13.5) respectively in the reach-to-grasp group and 4 (3.0,10.0), 6 (3.0,14.0) in the usual care group. Incidence of arm pain was similar between groups. The study was stopped before 11 patients reached the 24 weeks assessment. Conclusions: An RCT of home-based Reach-to-Grasp training after stroke is feasible and safe. With ARAT being our preferred measure it is estimated that 240 participants will be needed for a future two armed trial.
What palliative care–related problems do patients with drug-resistant or drug-susceptible tuberculosis experience on admission to hospital? A cross-sectional self-report study
Authors: Harding Richard , Defilippi Kath , Cameron David 
Published: July 2016

Background: The new World Health Organization’s ‘End TB’ strategy specifies palliative care within its strategic pillars. Limited data on patient-reported problems are available to inform an effective care response. Aim: We aimed to (1) identify most burdensome problems, (2) compare intensity of problems for drug-susceptible and drug-resistant tuberculosis and (3) identify predictors of problem identifiers. Design: Cross-sectional self-report quantitative study. Setting/participants: Self-report palliative care problems (physical, psychological, social and spiritual) were collected among patients on admission to a general district hospital with tuberculosis and multidrug-resistant tuberculosis wards in South Africa. Results: Totally, 114 patients were recruited. The items with worst score responses were worry (60.5%), pain (42.1%), help and advice to plan for the future (35.1%), symptoms (29.0%) and ability to share feelings (25.1%). In ordinal logistic regression, age was predictive of a higher (worse) score for total Palliative Outcome Scale total score (0.058, 95% confidence interval = 0.0018–0.099, p = 0.005) and Factor 2 (interpersonal wellbeing: 0.038, 95% confidence interval = 0.003–0.073, p = 0.031). Interestingly, multidrug-resistant tuberculosis was predictive of lower (better) score for both total Palliative Outcome Scale score and Factor 1 (physical and psychological wellbeing). Weight, human immunodeficiency virus status and prior treatment were not significantly associated with any of the three. Conclusion: Currently, patients with drug-susceptible tuberculosis are only admitted to hospital with complications, explaining their worse scores. The high burden of physical and psychosocial problems experienced by our sample provides strong evidence of the need for palliative care alongside potentially curative options.
Inpatient transfer to a care home for end-of-life care: What are the views and experiences of patients and their relatives? A systematic review and narrative synthesis of the UK literature
Authors: Thomas Tabitha , Kuhn Isla , Barclay Stephen 
Published: July 2016

Background: Transfers from hospital or ‘hospice palliative care units’ to care homes for end-of-life care are an increasingly common part of clinical practice but are a source of anxiety and distress for patients, relatives and healthcare professionals. Aim: To understand the experiences of patients discharged to care homes for end-of-life care. Design: Systematic review and narrative synthesis of the UK literature concerning inpatient transfer from a hospital or hospice palliative care unit to a care home for end-of-life care. Results: The published literature is very limited: only three papers and one conference abstract were identified, all of low quality using Gough’s weight of evidence assessment. No papers examined transfer from hospital: all were of transfers from hospices and were retrospective case note reviews. Many patients were reported to have been negative or ambivalent about moving and experienced feelings of anxiety or abandonment when transferred. Relatives were often either vehemently opposed or ambivalent. Although some came to accept transfer, others reported the transfer to have seriously affected their loved one’s quality of life and that the process of finding a care home had been traumatic. No studies investigated patients’ views prospectively, the views of staff or the processes of decision-making. Conclusion: The UK literature is very limited, despite such transfers being an increasingly common part of clinical practice and a source of concern to patients, relatives and staff alike. Further research is urgently needed in this area, especially studies of patients themselves, in order to understand their experiences and views.