bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reverse Engineering Field Isolates of Myxoma Virus Demonstrates that Some Gene Disruptions or Losses of Function Do Not Explain Virulence Changes Observed in the Field
Authors: Liu June , Cattadori Isabella M. , Sim Derek G. , Eden John-Sebastian , Holmes Edward C. , Read Andrew F. , Kerr Peter J. 
Published: August 2017

ABSTRACTThe coevolution of myxoma virus (MYXV) and wild European rabbits in Australia and Europe is a paradigm for the evolution of a pathogen in a new host species. Genomic analyses have identified the mutations that have characterized this evolutionary process, but defining causal mutations in the pathways from virulence to attenuation and back to virulence has not been possible. Using reverse genetics, we examined the roles of six selected mutations found in Australian field isolates of MYXV that fall in known or potential virulence genes. Several of these mutations occurred in genes previously identified as virulence genes in whole-gene knockout studies. Strikingly, no single or double mutation among the mutations tested had an appreciable impact on virulence. This suggests either that virulence evolution was defined by amino acid changes other than those analyzed here or that combinations of multiple mutations, possibly involving epistatic interactions or noncoding sequences, have been critical in the ongoing evolution of MYXV virulence. In sum, our results show that single-gene knockout studies of a progenitor virus can have little power to predict the impact of individual mutations seen in the field. The genetic determinants responsible for this canonical case of virulence evolution remain to be determined.IMPORTANCEThe species jump of myxoma virus (MYXV) from the South American tapeti to the European rabbit populations of Australia and Europe is a canonical example of host-pathogen coevolution. Detailed molecular studies have identified multiple genes in MYXV that are critical for virulence, and genome sequencing has revealed the evolutionary history of MYXV in Australia and Europe. However, it has not been possible to categorically identify the key mutations responsible for the attenuation of or reversion to virulence during this evolutionary process. Here we use reverse genetics to examine the role of mutations in viruses isolated early and late in the Australian radiation of MYXV. Surprisingly, none of the candidate mutations that we identified as likely having roles in attenuation proved to be important for virulence. This indicates that considerable caution is warranted when interpreting the possible role of individual mutations during virulence evolution.
Improving specialist palliative care in residential care for older people: a checklist to guide practice
Authors: Forbat Liz , Chapman Michael , Lovell Clare , Liu Wai-Man , Johnston Nikki 
Published: August 2017

ObjectivesPalliative care needs rounds are triage meetings that have been introduced in residential care for older adults to help identify and prioritise care for people most at risk for unplanned dying with inadequately controlled symptoms. This study sought to generate an evidence-based checklist in order to support specialist palliative care clinicians integrate care in residential nursing homes for older people.MethodsA grounded theory ethnographic study, involving non-participant observation and qualitative interviews. The study was conducted at four residential facilities for older people in one city. Observations and recordings of 15 meetings were made, and complimented by 13 interviews with staff attending the needs rounds.ResultsThe palliative care needs round checklist is presented, alongside rich description of how needs rounds are conducted. Extracts from interviews with needs rounds participants illustrate the choice of items within the checklist and their importance in supporting the evolution towards efficient and effective high-quality specialist palliative care input to the care of older people living in residential care.ConclusionsThe checklist can be used to support the integration of specialist palliative care into residential care to drive up quality care, provide staff with focused case-based education, maximise planning and reduce symptom burden for people at end of life.
Use of a 23-hour emergency department observation unit for the management of patients with toxic exposures
Authors: Mong Rupeng , Arciaga Gabriel Joseph , Tan Hock Heng 
Published: August 2017

BackgroundA significant proportion of patients with toxic exposures presenting to the ED require admission. However, most will improve within 24 hours, and so could potentially be managed in a short-stay observation unit. We describe the management and outcomes of these patients in a 23-hour ED observation unit (EDOU).MethodsA retrospective chart review of all patients with toxic exposures admitted to the EDOU in Singapore between 1 April 2013 and 31 March 2015 was performed. Patient demographics, exposure patterns, clinical presentation and interventions received were abstracted. The poisoning severity score (PSS) was retrospectively determined. Outcomes were length of stay and disposition.ResultsA total of 286 patients were analysed, of which 78.0% had intentional self-poisoning, 12.2% had bites/stings and 9.8% had unintentional or occupational toxic exposures. Analgesics (29.4%), sedatives (12.3%) and antidepressants (6.8%) were the most common drugs encountered. The majority of patients had a mild (68.9%) or moderate (15.4%) PSS, but 4.2% were graded as severe. Most patients with deliberate self-poisoning were reviewed by psychiatry (88.8%) and social services (74.9%). Most patients (92.0%) were medically cleared during their stay in EDOU, including all 12 with a severe PSS. Of these, 200 (69.9%) were discharged and 63 (22.0%) were transferred directly to a psychiatric unit. The median length of stay in the EDOU was 18 hours (IQR 13–23).ConclusionMost patients admitted to the EDOU were successfully managed and medically cleared within 23 hours, including those with a severe PSS. The EDOU appears to be a suitable alternative to inpatient admission for selected patients.
Casimir effect for the Higgs field at finite temperature
Authors: Santos A. F. , Khanna Faqir C. 
Published: August 2017

In early 1970, it was postulated that there exists a zero spin quantum field, called Higgs field, that is present in all universe. The potential energy of the Higgs field is transferred to particles. Hence they acquire mass. These ideas were essential in fulfilling the basic need for a particle, called Higgs, with mass. These particles are called Higgs particles with spin zero with its mass to be [Formula: see text][Formula: see text]125 GeV. This raises the question as to its physical effects. If these particles are present, will they exhibit a Casimir effect and also obey the Stefan–Boltzmann Law? Assuming the dynamics of this field, will these effects change with temperature. The present calculation uses thermo field dynamics formalism to calculate temperature effects.
Overactivation of intestinal sterol response element-binding protein 2 promotes diet-induced nonalcoholic steatohepatitis
Authors: Malhotra Pooja , Aloman Costica , Ankireddy Aparna , Khadra Hani , Ooka Kohtaro , Gill Ravinder K. , Saksena Seema , Dudeja Pradeep K. , Alrefai Waddah A. 
Published: August 2017

Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver that may progress to hepatic fibrosis and nonalcoholic steatohepatitis (NASH). Mechanisms underlying NAFLD and NASH are not yet fully understood. Dietary cholesterol was recently shown to be a risk factor for the development of NASH, suggesting a role for intestinal handling of cholesterol. One important regulator of cholesterol homeostasis is the sterol response element-binding protein-2 (SREBP-2) transcription factor. We tested the hypothesis that the overactivation of intestinal SREBP-2 increases the susceptibility to diet-induced NASH. A transgenic mouse model with intestine-specific overexpression of active SREBP-2 (ISR2 mice) driven by villin promoter was used. ISR2 mice and their wild-type littermates were fed a regular chow diet or a high-fat, high-cholesterol (HFHC) diet (15% fat, 1% cholesterol) for 15 wk. Results showed that HFHC feeding to ISR2 mice caused hepatic inflammation with increased levels of proinflammatory cytokines. Histological examination demonstrated extensive fibrosis after a HFHC diet associated with a perivascular as well as pericellular collagen deposits in ISR2 mice compared with wild-type littermates. The severe hepatic inflammation and advanced fibrosis in ISR2 mice was not associated with a difference in lipid accumulation in ISR2 mice compared with wild type littermates after HFHC feeding. These data indicate that overactivation of intestinal SREBP2 promotes diet-induced hepatic inflammation with features of human NASH resulting in rapid severe fibrosis and provide a novel link between regulatory processes of intestinal cholesterol and progression of fatty liver. NEW & NOTEWORTHY The current study highlights the role of overactivation of intestinal SREBP-2 transcription factor in the progression of hepatic fibrosis associated with diet-induced NASH. Mice with intestine-specific overexpression of SREBP-2 demonstrated more inflammation and severe fibrosis in the liver in response to 15 wk of being fed a high-cholesterol, high-fat diet as compared with their wild-type littermates. These data demonstrate a novel link between intestinal regulatory processes of cholesterol metabolism and the pathogenesis of fatty liver diseases.
Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban
Authors: Janion-Sadowska Agnieszka , Natorska Joanna , Siudut Jakub , Zabczyk Michal , Stanisz Andrzej , Undas Anetta 
Published: August 2017

SummaryWe sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2–6 hours (h) after and 20–25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks −12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2–6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT −25 % and −25 %, CLT-TAFI −20 % and −24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks −12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20–25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.
Downregulation of hypoxia-inducible factor-1α contributes to impaired megakaryopoiesis in immune thrombocytopenia
Authors: Pan Tingting , Wang Qi , Zhu Li , Qi Jiaqian , You Tao , Han Yue 
Published: August 2017

SummaryImpaired megakaryocyte maturation and exaggerated platelet destruction play a pivotal role in the pathogenesis of immune thrombocytopenia (ITP). Previous studies have shown that HIF-1α promotes the homing and engraftment of haematopoietic stem cells (HSCs), thereby stimulating HSC differentiation. However, whether HIF-1α plays a role in megakaryocytic maturation and platelet destruction in ITP remains elusive. Using enzyme-linked immunosorbent assays (ELISAs), we demonstrated that there were lower HIF-1α levels in the bone marrow (BM) of ITP patients than in that of healthy donors and patients with chemotherapy-related thrombocytopenia. Subjects with lower megakaryocyte (<100/slide) and platelet (<30 × 109/L) counts exhibited significantly decreased BM HIF-1α levels, compared to those with higher megakaryocyte (≥100/slide) and platelet (≥30 × 109/L) counts. To test whether HIF-1α regulates megakaryopoiesis and platelet production, megakaryocytes derived from mouse BM cells were treated with an HIF-1α activator (IOX-2; 50 µM) or inhibitor (PX-478; 50 µM). PX-478 significantly decreased HIF-1α expression, cell size, and the populations of CD41-positive and high-ploidy cells. Importantly, to evaluate the role of HIF-1α as a potential therapeutic target in ITP, mouse BM cells were incubated with plasma from ITP patients in the presence or absence of IOX-2. IOX-2 significantly attenuated the ITP plasma-induced decrease in cell size as well as the proportions of CD41-positive and high-ploidy cells. In addition, IOX-2 increased the number of megakaryocytes from mouse BM cells treated with ITP plasma. Our findings indicate that decreased HIF-1α may contribute to impaired megakaryopoiesis in ITP, and HIF-1α may provide a potential therapy for ITP patients.Supplementary Material to this article is available online at www.thrombosis-online.com.
Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor
Authors: Zafar M. Urooj , Smith Donald A. , Baber Usman , Sartori Samantha , Chen Kevin , Lam David W. , Linares-Koloffon Carlos A. , Rey-Mendoza Juan , Jimenez Britez Gustavo , Escolar Gines , Fuster Valentin , Badimon Juan J. 
Published: August 2017

Background—

American College of Cardiology/American Heart Association guidelines advise waiting 5 to 7 days before operating on P2Y
12
inhibitor-treated acute coronary syndrome patients, to allow dissipation of its antiplatelet effects. Platelet transfusion is often used to restore hemostasis during operations, but its effectiveness and optimal timing are unclear. We investigated the degree of functional gains obtained from platelet supplementation after loading and maintenance of dual antiplatelet therapy with ticagrelor and the influence of timing on this strategy.

Methods and Results—

After baseline platelet testing (Multiplate Analyzer and VerifyNow), cardiovascular disease patients (n=20; 56.9±7.9 years; 65% men; 75% diabetic) received dual antiplatelet therapy as a single loading dose (ticagrelor 180 mg plus aspirin 325 mg) and as daily/maintenance treatment for 5 to 7 days (maintenance therapy: ticagrelor 90 mg BID plus aspirin 81 mg QD). At 4, 6, 24, and 48 hours from (last) dosing, patients’ blood samples were supplemented with concentrated platelets from healthy donors in vitro, raising platelet counts by 0% (unsupplemented control), 25%, 50%, and 75%, and the function retested. Reactivity in supplemented samples was compared with respective 0% sample and with the pretreatment baseline. Results under loading dose and maintenance therapy regimens were nearly identical. Platelet reactivity was higher (
P
<0.05) in nearly all supplemented samples versus respective controls. Aggregations with supplementation were 59% to 79% of baseline at 24 hours and equal to baseline at 48 hours.

Conclusions—
Platelet reactivity of ticagrelor-treated patients can be restored using concentrated platelets after a loading dose/maintenance therapy in a time-dependent manner under in vitro testing. Although statistically significant improvements are evident 6 hours after (last) dosing, ≥24 hours maybe needed for clinically meaningful restoration in platelet function.

Clinical Trial Registration—

URL:
https://clinicaltrials.gov
. Unique identifier: NCT02201394.
Optimized Screening of Coronary Artery Disease With Invasive Coronary Angiography and Ad Hoc Percutaneous Coronary Intervention During Transcatheter Aortic Valve Replacement
Authors: Barbanti Marco , Todaro Denise , Costa Giuliano , Pilato Gerlando , Picci Andrea , Gulino Simona , Capranzano Piera , La Spina Ketty , Di Simone Emanuela , D’Arrigo Paolo , Deste Wanda , Indelicato Antonino , Cannata Stefano , Giannazzo Daniela , Immè Sebastiano , Tamburino Claudia , Patanè Martina , Buccheri Sergio , Capodanno Davide , Sgroi Carmelo , Tamburino Corrado 
Published: August 2017

Background—
We sought to describe an optimized approach to coronary artery disease (CAD) screening and management in patients undergoing transcatheter aortic valve replacement (TAVR).

Methods and Results—

When invasive coronary angiography showed CAD, the treatment strategy and completeness of revascularization was determined based on coronary anatomy. TAVR was performed in the same setting if percutaneous coronary intervention (PCI) was uncomplicated; otherwise TAVR was postponed. A total of 604 patients undergoing CAD screening at the time of TAVR procedure were prospectively included in this study. Severe CAD was found in 136 patients (22.5%). Among patients with severe CAD, 53 patients (8.8%) underwent uncomplicated PCI. After PCI, TAVR was postponed in 2 patients (0.3%). In 83 patients (13.8%), coronary angiography showed severe CAD that was left untreated. After TAVR, all-cause and cardiovascular 30-day mortality rates were 2.4% and 1.4%, respectively. Disabling stroke, myocardial infarction, and life-threatening bleeding occurred in 0.5%, 0.8%, and 4.0% of patients, respectively. Acute kidney injury II or III rate was 3.3%. At 2 years, all-cause mortality rate was 14.1%. Disabling stroke and myocardial infarction occurred in 2.5% and 1.8% of patients, respectively. Patients undergoing TAVR and PCI in the same session had similar rate of the composite of death, disabling stroke, and myocardial infarction when compared with patients without CAD, and patients with severe CAD left untreated (TAVR+PCI: 10.4%; severe CAD left untreated: 15.4%; no-CAD: 14.8%;
P
=0.765).

Conclusions—
In patients undergoing TAVR, screening of CAD with invasive coronary angiography and ad hoc PCI during TAVR is feasible and was not associated with increased periprocedural risks. PCI followed by TAVR in the same session had similar outcomes than TAVR in which PCI was not performed.
Age and Sex Disparities in Discharge Statin Prescribing in the Stroke Belt: Evidence From the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Albright Karen C. , Howard Virginia J. , Howard George , Muntner Paul , Bittner Vera , Safford Monika M. , Boehme Amelia K. , Rhodes J. David , Beasley T. Mark , Judd Suzanne E. , McClure Leslie A. , Limdi Nita , Blackburn Justin 
Published: August 2017

Background
Stroke is a costly and debilitating disease that disproportionately affects blacks. Despite the efficacy of statins, evidence suggests racial disparities may exist in statin prescribing.

Methods and Results

We analyzed discharge medications for participants hospitalized for an ischemic stroke during follow‐up of the
REGARDS
(Reasons for Geographic and Racial Differences in Stroke) study. Medications on admission and discharge were abstracted from medical records. Among the 666 eligible incident strokes (2003–2013), analyses were restricted to 323 participants who were not statin users at the time of admission and had no history of atrial fibrillation. Overall, 48.7% were prescribed a statin on discharge. In the Stroke Belt, participants aged 65 years and older were 47% less likely to be discharged on a statin compared with those younger than 65 years (relative risk [
RR
], 0.53; 95%
CI
, 0.38–0.74). This association was not observed in non–Stroke Belt residents. Outside the Stroke Belt, blacks were more likely than whites to be discharged on a statin (
RR
, 1.42; 95%
CI
, 1.04–1.94), while no black:white association was present among Stroke Belt residents (
RR
, 0.93; 95%
CI
, 0.69–1.26;
P
for interaction=0.228). Compared with women, men in the Stroke Belt were 31% less likely to be discharged on a statin (
RR
, 0.69; 95%
CI
, 0.50–0.94) while men outside the Stroke Belt were more likely to be discharged on a statin (
RR
, 1.38; 95%
CI
, 0.99–1.92;
P
for interaction=0.004).

Conclusions
Statin discharge prescribing may differ among Stroke Belt and non–Stroke Belt residents, particularly in older Americans and men.
Utilization of Statins Beyond the Initial Period After Stroke and 1‐Year Risk of Recurrent Stroke
Authors: Lee Meng , Saver Jeffrey L. , Wu Yi‐Ling , Tang Sung‐Chun , Lee Jiann‐Der , Rao Neal M. , Wang Hui‐Hsuan , Jeng Jiann‐Shing , Lee Tsong‐Hai , Chen Pei‐Chun , Ovbiagele Bruce 
Published: August 2017

Background
In‐hospital discontinuation of statins has been linked to poorer early stroke outcomes, but the consequences of postdischarge discontinuation or dose reduction of statin treatment are unknown. The objective of this study was to explore the effects of statin discontinuation or statin dose reduction on recurrent stroke risk.

Methods and Results

We conducted a nationwide cohort study using the data from the Taiwan National Health Insurance Research Database. Our source population comprised all patients who were prescribed a statin within 90 days of discharge after an ischemic stroke between 2001 and 2012. Patients were categorized into 3 groups: statin‐discontinued, statin‐reduced, and statin‐maintained. Cox proportional hazard models were used to estimate the hazard ratios and 95%
CI
s of recurrent stroke during 1‐year follow‐up in the groups who discontinued statins or reduced statin dose compared with the group who maintained statins as the reference. Among the 45 151 ischemic stroke patients meeting criteria, during the day‐90 to day‐180 period, 7.0% were on reduced statin therapy, and 18.5% were not on any statin therapy. Compared with maintained‐statin intensity therapy, discontinuation of statins was associated with an increased hazard of recurrent stroke (adjusted hazard ratio 1.42, 95%
CI
1.28‐1.57), whereas reduced‐statin dose was not associated with an additional risk (adjusted hazard ratio 0.94, 95%
CI
0.78‐1.12). Propensity‐matching analysis obtained similar results.

Conclusions
Discontinuation of statin therapy between 3 and 6 months after an index ischemic stroke was associated with a higher risk of recurrent stroke within 1 year after statin discontinuation.
A New Technique to Estimate Sensible Heat Fluxes around Micrometeorological Towers Using Small Unmanned Aircraft Systems
Authors: Lee Temple R. , Buban Michael , Dumas Edward , Baker C. Bruce 
Published: August 2017

AbstractUpscaling point measurements from micrometeorological towers is a challenging task that is important for a variety of applications, for example, in process studies of convection initiation, carbon and energy budget studies, and the improvement of model parameterizations. In the present study, a technique was developed to determine the horizontal variability in sensible heat flux H surrounding micrometeorological towers. The technique was evaluated using 15-min flux observations, as well as measurements of land surface temperature and air temperature obtained from small unmanned aircraft systems (sUAS) conducted during a one-day measurement campaign. The computed H was found to be comparable to the micrometeorological measurements to within 5–10 W m−2. Furthermore, when comparing H computed using this technique with H determined using large-eddy simulations (LES), differences of <10 W m−2 were typically found. Thus, implementing this technique using observations from sUAS will help determine sensible heat flux variability at horizontal spatial scales larger than can be provided from flux tower measurements alone.