bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Platelet Protein Ubiquitylation and Changes following GPVI Activation
Authors: Unsworth Amanda , Bombik Izabela , Pinto-Fernandez Adan , McGouran Joanna , Konietzny Rebecca , Zahedi René , Watson Steve , Kessler Benedikt , Pears Catherine 
Published: December 2018

AbstractPlatelet activators stimulate post-translational modification of signalling proteins to change their activity or their molecular interactions leading to signal propagation. One covalent modification is attachment of the small protein ubiquitin to lysine residues in target proteins. Modification by ubiquitin can either target proteins for degradation by the proteasome or act as a scaffold for other proteins. Pharmacological inhibition of deubiquitylases or the proteasome inhibition of platelet activation by collagen, demonstrating a role for ubiquitylation, but relatively few substrates for ubiquitin have been identified and the molecular basis of inhibition is not established. Here, we report the ubiquitome of human platelets and changes in ubiquitylated proteins following stimulation by collagen-related peptide (CRP-XL). Using platelets from six individuals over three independent experiments, we identified 1,634 ubiquitylated peptides derived from 691 proteins, revealing extensive ubiquitylation in resting platelets. Note that 925 of these peptides show an increase of more than twofold following stimulation with CRP-XL. Multiple sites of ubiquitylation were identified on several proteins including Syk, filamin and integrin heterodimer sub-units. This work reveals extensive protein ubiquitylation during activation of human platelets and opens the possibility of novel therapeutic interventions targeting the ubiquitin machinery.
tPA Point Mutation at Autolysis Loop Enhances Resistance to PAI-1 Inhibition and Catalytic Activity
Authors: Peng Shuangzhou , Xue Guangpu , Chen Shanli , Chen Zhuo , Yuan Cai , Li Jinyu , Huang Mingdong 
Published: December 2018

AbstractRecombinant tissue-type plasminogen activator (r-tPA) was approved by U.S. Food and Drug Administration as a thrombolytic drug. However, a high dose of r-tPA (up to 100 mg/person) is typically used in clinical applications. Such high dosage leads to severe side effects including haemorrhage and neurotoxicity, which can be fatal. To improve the proteolytic properties of tPA to enhance thrombolytic therapy, we designed a series of mutants in tPA serine protease domain (tPA-SPD) based on the crystal structure of tPA-SPD:plasminogen activators inhibitor-1 (PAI-1) complex that we determined recently. We found that the A146Y substitution in tPA-SPD(A146Y) enhanced resistance to PAI-1 inactivation by 30-fold compared with original tPA-SPD. Interestingly, the tPA-SPD(A146Y) variant showed fivefold higher activation for plasminogen compared with tPA-SPD. The variant also demonstrated thrombolytic activity stronger than tPA-SPD in a clot lysis assay. In vivo, we showed tPA-SPD(A146Y) possessed higher thrombolytic efficacy in a pulmonary embolism model compared with original tPA-SPD. Furthermore, a mouse tail bleeding assay showed that tPA-SPD(A146Y) did not increase bleeding risk compared with clinical drug r-tPA. Together, our findings reveal novel functions of A146Y variant, which not only increases the catalytic efficiency of the enzyme, but also enhances resistance to PAI-1 inhibition, and demonstrating that tPA-SPD (A146Y) variant is a much improved agent for thrombolytic therapy.
Effect of Multiple Doses of Oral Tranexamic Acid on Haemostasis and Inflammatory Reaction in Total Hip Arthroplasty: A Randomized Controlled Trial
Authors: Wang Duan , Yang Yang , He Chuan , Luo Ze-Yu , Pei Fu-Xing , Li Qi , Zhou Zong-Ke , Zeng Wei-Nan 
Published: December 2018

AbstractTranexamic acid (TXA) reduces surgical blood loss and alleviates inflammatory response in total hip arthroplasty. However, studies have not identified an optimal regimen. The objective of this study was to identify the most effective regimen of multiple-dose oral TXA in achieving maximum reduction of blood loss and inflammatory response based on pharmacokinetic recommendations. We prospectively studied four multiple-dose regimens (60 patients each) with control group (group A: matching placebo). The four multiple-dose regimens included: 2-g oral TXA 2 hours pre-operatively followed by 1-g oral TXA 3 hours post-operatively (group B), 2-g oral TXA followed by 1-g oral TXA 3 and 7 hours post-operatively (group C), 2-g oral TXA followed by 1-g oral TXA 3, 7 and 11 hours post-operatively (group D) and 2-g oral TXA followed by 1-g oral TXA 3, 7, 11 and 15 hours post-operatively (group E). The primary endpoint was estimated blood loss on post-operative day (POD) 3. Secondary endpoints were thromboelastographic parameters, inflammatory components, function recovery and adverse events. Groups D and E had significantly less blood loss on POD 3, with no significant difference between the two groups. Group E had the most prolonged haemostatic effect, and all thromboelastographic parameters remained within normal ranges. Group E had the lowest levels of inflammatory cytokines and the greatest range of motion. No thromboembolic complications were observed. The post-operative four-dose regimen brings about maximum efficacy in reducing blood loss, alleviating inflammatory response and improving analgaesia and immediate recovery.
Early-Onset Neonatal Sepsis and Antibiotic Use in Northeast Thailand
Authors: Kiatchoosakun Pakaphan , Jirapradittha Junya , Sirikarn Prapassara , Laopaiboon Malinee , Pattanittum Porjai , Chandrakachorn Woranart , Srirojana Sakulrat , Jeffery Heather , Green Sally , Lumbiganon Pagakrong ,   on behalf of the SEA-URCHIN Study Group
Published: December 2018

Objective Antibiotics are commonly prescribed in neonatal intensive care units (NICUs) for suspected sepsis because of the nonspecific clinical symptoms of sepsis. The overuse of antibiotic is associated with adverse outcomes. This study aimed to determine the rate of early-onset sepsis (EOS) and antibiotic use in neonates admitted to three NICUs in Northeast Thailand
Study Design This is a descriptive study using the data collected in the South East Asia—Using Research for Change in Hospital-acquired Infection in Neonates project. Neonates admitted within 3 days of life were included. EOS was defined as neonates who presented with three or more clinical signs or laboratory results suggested sepsis and received antibiotics for at least 5 days. Those with positive blood culture were culture-proven EOS. Antibiotic use within 3 days of life and up to 28 days was described.
Results Among 1,897 neonates, 160 cases were classified as EOS (8.4%) with culture-proven EOS in 4 cases (0.2%). The median durations of antibiotic use in culture-proven and culture-negative EOSs were 15 and 8 days, respectively.
Conclusion The rate of culture-proven EOS was low, but there was a high rate of antibiotic use. Antibiotic stewardship should be emphasized.
Renal Parenchymal Disease Mimicking Preeclampsia
Authors: Paul Sashikala , Garre Indrani , Achukatla Kumar 
Published: December 2018

AbstractA 28-year-old primigravida woman, who was diagnosed with preeclampsia and managed with calcium channel blockers during the pregnancy for control of hypertension, was referred to the cardiologist 2 weeks after the pregnancy for management of accelerated hypertension. Preeclampsia diagnosis is substantiated by detecting hypertension in the 20th week of pregnancy, pedal edema, proteinuria, and liver enzyme abnormalities. A subsequent evaluation found that the patient had shrunken kidney, perhaps due to chronic pyelonephritis. Physicians always have to keep in mind to detect the secondary cause of hypertension in a pregnant woman.
1.0 GPa low carbon medium Mn heavy steel plate with excellent ductility
Authors: Chen Jun , Ren Jia-kuan , Liu Zhen-yu , Wang Guo-dong 
Published: December 2018

A vanadium-bearing medium Mn heavy steel plate was designed, and the yield strength reaches around 1.0 GPa and the total elongation reaches around 18% after the annealing treatments. Meanwhile, the steel also possesses relatively good cryogenic impact toughness. Although the dislocation density of ∼2.65 × 1014 m−2 in the hot-rolled steel decreases to ∼1.13 × 1014 m−2 in both annealed steels and the volume fractions of retained austenite reach ∼7.9% and ∼13.5% for the steels annealed at 620°C for 1 and 2 h, there is no or small decrease in yield strength owing to numerous nanometer-sized carbides precipitated in martensite matrix. This paper is part of a Thematic Issue on Medium Manganese Steels.
Effect of thermal radiation and heat absorption of MHD Casson nanofluid over a stretching surface in a porous medium with convective heat and mass conditions
Authors: Eswaramoorthi S , Sivasankaran S , Alshomrani Ali Saleh 
Published: December 2018

Abstract
This article explores the impact of radiation and heat absorption on magneto-convective flow of Casson nanofluid over a stretching surface in a porous medium. The convective heat and mass boundary conditions are also taken into consideration in this study. The governing models are converted into a nonlinear ODE models and they are solved analytically using homotopy analysis method (HAM). The significance of physical parameters on velocity, temperature and nano particle volume fraction are discussed graphically.
Thermosolutal combined convection in a lid-driven enclosure with time periodic heating and linearly salting
Authors: Ananthan S. S. , Sivasankaran S. , Bhuvaneswari M. , Hakeem A. K. Abdul 
Published: December 2018

Abstract
Thermosoutal combined convective flow with mass and energy transport in a lid-driven enclosure box with discrete time periodic heating and linearly varying mass transfer is numerically investigated. The segment of the left wall is heating periodically in time and the right wall is preserved at a lower temperature. The top and bottom walls are thermally insulated. Two different concentrations are imposed along the left and right walls. The mathematical systems are solved by finite volume method. The results are obtained for various values of factors, like, Richardson number, period and amplitude. It is observed that the oscillating frequency of averaged Nusselt number diminishes with raise in the period in the forced and free convection modes. The averaged Sherwood number rises as amplitude raise in the free convection mode. It is also attained that both averaged Sherwood and Nusselt numbers are diminished on raising the Richardson number.
Impacts of chemical reaction on MHD double diffusive flow with suction/blowing and slip
Authors: Malarselvi A. , Bhuvaneswari M. , Sivasankaran S. , Ganga B. , Hakeem A.K. Abdul 
Published: December 2018

Abstract
Unsteady double diffusive chemically reactive MHD thin fluid layer flow near the surface of an electrically conducting fluid with incompressibility past a flat surfaced plate is investigated by similarity analysis. The mathematically formulated PDEs are converted into ODEs by utilizing the similarity transforms. Then the numerical solution is determined for ODEs by operating Runge-Kutta method together with shooting technique. The impacts of varieties of parameters are scrutinized on stream velocity, energy distribution and solute dispensation through portraits. The inspection for the magnitude of local skin drag, rate of energy and solute transfer is executed through table.
Effective Heat-Insulating Solutions
Authors: Zagorodnuk L.Kh. , Sumskoy D.A. , Chepenko A.S. 
Published: December 2018

Abstract
The paper presents the results of the study devoted tothe reduction of perlite wastesin size in a vortex jet mill, as well as their reduction features. The bonding compositions were obtained at various ratios of cement and perlitesand wastes in a vortex jet mill at different reduction modes. Peculiarities of reduction processes were studied and technological and physical-mechanical properties of obtained bonding compositions were defined. The electron microscopy made it possible to study microstructures of cement stones received from taggedPortland cement and bonding compositions in a vortex jet mill. It was established that the open pores of cement bonding compositions prepared using perlite aggregates are always filled with new growths at various stages of collective growth. The microstructure of bonding compositions has dense structure due to rationally selectedcontent, use of effective mineral aggregates, i.e. perlite wastes thus creating additional substrates for the formation of an internal microstructure of a composite, mechanochemical activation of raw mix allowing obtaining composites with prescribed properties.
Effects of Media Exposure to Conflicting Information About Mammography: Results From a Population-based Survey Experiment
Authors: Nagler Rebekah H , Yzer Marco C , Rothman Alexander J 
Published: December 2018

Abstract

Background
Although there is growing theoretical and empirical support for the proposition that media exposure to conflicting health information negatively influences public understanding and behavior, few studies have causally linked exposure to conflict with undesirable outcomes. Such outcomes might be particularly likely in the context of mammography, given widespread media attention to conflicting recommendations about the age at and frequency with which average-risk women should be screened for breast cancer.

Purpose
The current study tests whether exposure to conflicting information about mammography negatively influences women’s affective and cognitive responses and examines whether effects vary by socioeconomic position.

Methods
We conducted an online survey experiment in 2016 with a population-based sample of U.S. women aged 35–55 (N = 1,474). Participants were randomly assigned to one of four conditions that differed in the level of conflict about mammography presented in a news story (no, low, medium, or high conflict), stratifying by poverty level.

Results
Greater exposure to conflict increased women’s negative emotional responses to the story they read, their confusion about and backlash toward cancer prevention recommendations and research, and their ambivalence about mammography and other types of cancer screening, though ambivalence leveled off at high levels of exposure. There was little evidence that effects varied across socioeconomic position.

Conclusions
Findings add to the growing evidence base documenting undesirable outcomes of exposure to conflicting health information. Future research should examine whether the negative affective and cognitive responses observed translate into behavior, which could have implications for both health campaigns and patient-provider communication.
BreakID: genomics breakpoints identification to detect gene fusion events using discordant pairs and split reads
Authors: Jin Linfang , Lai Jinhuo , Zhang Yang , Fu Ying , Wang Shuhang , Dai Heng , Huang Bingding 
Published: December 2018

Abstract

Summary
Here we developed a tool called Breakpoint Identification (BreakID) to identity fusion events from targeted sequencing data. Taking discordant read pairs and split reads as supporting evidences, BreakID can identify gene fusion breakpoints at single nucleotide resolution. After validation with confirmed fusion events in cancer cell lines, we have proved that BreakID can achieve high sensitivity of 90.63% along with PPV of 100% at sequencing depth of 500× and perform better than other available fusion detection tools. We anticipate that BreakID will have an extensive popularity in the detection and analysis of fusions involved in clinical and research sequencing scenarios.

Availability and implementation
Source code is freely available at https://github.com/SinOncology/BreakID.

Supplementary information
Supplementary data are available at Bioinformatics online.
Characteristics of Campylobacter and Salmonella Infections and Acute Gastroenteritis in Older Adults in Australia, Canada, and the United States
Authors: White Alice E , Ciampa Nadia , Chen Yingxi , Kirk Martyn , Nesbitt Andrea , Bruce Beau B , Walter Elaine Scallan 
Published: December 2018

Abstract

Background
The early detection of enteric infections in older adults is challenging because typical signs and symptoms of disease may be less common, absent, or overlooked. Understanding illness characteristics of enteric infections among older adults could improve the timeliness and accuracy of clinical diagnoses, thereby improving patient outcomes and increasing cases reported to surveillance.

Methods
Here, we describe illness characteristics (percentage reporting bloody diarrhea, fever, vomiting, abdominal pain; percentage hospitalized; duration of hospitalization; and duration of illness) among older adults (≥65 years) with acute gastroenteritis and culture-confirmed Campylobacter and nontyphoidal Salmonella infections in Australia, Canada, and the United States and compare these characteristics with those among younger people (<5 years, 5–24 years, and 25–64 years).

Results
A significant negative correlation was found between all symptoms and increasing age group, except for bloody diarrhea in cases of acute gastroenteritis. Adults aged ≥85 years reported bloody diarrhea in only 9% of nontyphoidal Salmonella and 4% of Campylobacter infections compared with 59% and 55% among children aged <5 years. Conversely, a greater percentage of older adults (≥65) than younger persons (<5, 5–24, 25–64) reported being hospitalized, with an increasing linear relationship in age groups 65 years and older.

Conclusions
Although older adults are more likely to have severe illness and be hospitalized, we found that the proportion of persons reporting symptoms typically associated with enteric infections decreases with age. These findings have implications for clinical recognition and treatment of gastrointestinal illness, as well as for public health research.
Preemptive endoluminal vacuum therapy to reduce anastomotic leakage after esophagectomy: a game-changing approach?
Authors: Gubler C , Vetter D , Schmidt H M , Müller P C , Morell B , Raptis D , Gutschow C A 
Published: December 2018

Summary
Endoluminal vacuum therapy (EVT) is an accepted treatment for anastomotic leakage (AL) after esophagectomy. A novel concept is to use this technology in a preemptive setting, with the aim to reduce the AL rate and postoperative morbidity. Preemptive EVT (pEVT) was performed intraoperatively in 19 consecutive patients undergoing minimally invasive esophagectomy, immediately after completion of esophagogastrostomy. Twelve patients (63%) were high-risk cases with severe comorbidity. The EVT device was removed routinely three to six (median 5) days after esophagectomy. The endpoints of this study were AL rate and postoperative morbidity. There were 20 anastomoses at risk in 19 patients. One patient (5.3%) experienced major morbidity (Clavien–Dindo grade IIIb) unrelated to anastomotic healing. He underwent open reanastomosis at postoperative day 12 with pEVT for redundancy of the gastric tube and failure of transition to oral diet. Mortality after 30 days was 0% and anastomotic healing was uneventful in 19/20 anastomoses (95%). One minor contained AL healed after a second course of EVT. Except early proximal dislodgement in one patient, there were no adverse events attributable to pEVT. The median comprehensive complication index 30 days after surgery was 20.9 (IQR 0–26.2). PEVT appears to be a safe procedure that may have the potential to improve surgical outcome in patients undergoing esophagectomy.
Extracorporeal membrane oxygenation for right ventricular failure following pericardiectomy
Authors: Ahmad Hasham , Porter Richard , Yusuff Hakeem , Roman Marius 
Published: December 2018

Abstract
We report the case of a 61-year-old gentleman who underwent pericardiectomy for constrictive pericarditis. Constrictive pericarditis was diagnosed through echocardiogram, computed tomography chest and cardiac magnetic resonance imaging. An elective decision was made for commencing venoarterial extracorporeal membrane oxygenation (ECMO) immediately postoperatively to prevent significant right ventricular failure (RVF). Postoperatively, the patient remained on ECMO for 4 days in a stable condition, showing no further signs of RVF. Venoarterial ECMO may be of use as an elective adjunct in cases at high risk of RVF following pericardiectomy.
Impact of Epithelial–Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ
Authors: Strell Carina , Paulsson Janna , Jin Shao-Bo , Tobin Nicholas P , Mezheyeuski Artur , Roswall Pernilla , Mutgan Ceren , Mitsios Nicholas , Johansson Hemming , Wickberg Sarah Marie , Svedlund Jessica , Nilsson Mats , Hall Per , Mulder Jan , Radisky Derek C , Pietras Kristian , Bergh Jonas , Lendahl Urban , Wärnberg Fredrik , Östman Arne 
Published: December 2018

AbstractBackgroundA better definition of biomarkers and biological processes related to local recurrence and disease progression is highly warranted for ductal breast carcinoma in situ (DCIS). Stromal–epithelial interactions are likely of major importance for the biological, clinical, and pathological distinctions between high- and low-risk DCIS cases.MethodsStromal platelet derived growth factor receptor (PDGFR) was immunohistochemically assessed in two DCIS patient cohorts (n = 458 and n = 80). Cox proportional hazards models were used to calculate the hazard ratios of recurrence. The molecular mechanisms regulating stromal PDGFR expression were investigated in experimental in vitro co-culture systems of DCIS cells and fibroblasts and analyzed using immunoblot and quantitative real-time PCR. Knock-out of JAG1 in DCIS cells and NOTCH2 in fibroblasts was obtained through CRISPR/Cas9. Experimental data were validated by mammary fat pad injection of DCIS and DCIS-JAG1 knock-out cells (10 mice per group). All statistical tests were two-sided.ResultsPDGFRα(low)/PDGFRβ(high) fibroblasts were associated with increased risk for recurrence in DCIS (univariate hazard ratio = 1.59, 95% confidence interval [CI] = 1.02 to 2.46; P = .04 Wald test; multivariable hazard ratio = 1.78, 95% CI = 1.07 to 2.97; P = .03). Tissue culture and mouse model studies indicated that this fibroblast phenotype is induced by DCIS cells in a cell contact-dependent manner. Epithelial Jagged1 and fibroblast Notch2 were identified through loss-of-function studies as key juxtacrine signaling components driving the formation of the poor prognosis-associated fibroblast phenotype.ConclusionsA PDGFRα(low)/PDGFRβ(high) fibroblast subset was identified as a marker for high-risk DCIS. The Jagged-1/Notch2/PDGFR stroma–epithelial pathway was described as a novel signaling mechanism regulating this poor prognosis-associated fibroblast subset. In general terms, the study highlights epithelial–stromal crosstalk in DCIS and contributes to ongoing efforts to define clinically relevant fibroblast subsets and their etiology.