bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut Microbiota-Associated Activation of TLR5 Induces Apolipoprotein A1 Production in the Liver
Authors: Yiu Jensen H.C. , Chan Kam-Suen , Cheung Jamie , Li Jin , Liu Yan , Wang Yao , Fung William W.L. , Cai Jieling , Cheung Samson W.M. , Dorweiler Bernhard , Wan Eric Y.F. , Tso Patrick , Xu Aimin , Woo Connie W. 
Published: August 2020

Rationale:
Dysbiosis of gut microbiota plays an important role in cardiovascular diseases but the molecular mechanisms are complex. An association between gut microbiome and the variance in HDL-C (high-density lipoprotein-cholesterol) level was suggested in a human study. Besides, dietary fat was shown to increase both HDL-C and LDL-C (low-density lipoprotein-cholesterol) levels. We speculate that certain types of gut bacteria responding to dietary fat may help to regulate HDL-C level and potentially affect atherosclerotic development.

Objective:
We aimed to investigate whether and how high-fat diet (HFD)-associated gut microbiota regulated HDL-C level.

Methods and Results:

We found that HFD increased gut flagellated bacteria population in mice. The increase in HDL-C level was adopted by mice receiving fecal microbiome transplantation from HFD-fed mouse donors. HFD led to increased hepatic but not circulating flagellin, and deletion of TLR5 (Toll-like receptor 5), a receptor sensing flagellin, suppressed HFD-stimulated HDL-C and ApoA1 (apolipoprotein A1) levels. Overexpression of TLR5 in the liver of TLR5-knockout mice was able to partially restore the production of ApoA1 and HDL-C levels. Mechanistically, TLR5 activation by flagellin in primary hepatocytes stimulated ApoA1 production through the transcriptional activation responding to the binding of NF-κB (nuclear factor-κB) on
Apoa1
promoter region. Furthermore, oral supplementation of flagellin was able to stimulate hepatic ApoA1 production and HDL-C level and decrease atherosclerotic lesion size in apolipoprotein E-deficient (
Apoe
−/−
) mice without triggering hepatic and systemic inflammation. The stimulation of ApoA1 production was also seen in human ApoA1-transgenic mice treated with oral flagellin.

Conclusions:
Our finding suggests that commensal flagellated bacteria in gut can facilitate ApoA1 and HDL-C productions in liver through activation of TLR5 in hepatocytes. Hepatic TLR5 may be a potential drug target to increase ApoA1.
General Versus Local Anesthesia With Conscious Sedation in Transcatheter Aortic Valve Implantation
Authors: Thiele Holger , Kurz Thomas , Feistritzer Hans-Josef , Stachel Georg , Hartung Philipp , Lurz Philipp , Eitel Ingo , Marquetand Christoph , Nef Holger , Doerr Oliver , Vigelius-Rauch Ursula , Lauten Alexander , Landmesser Ulf , Treskatsch Sascha , Abdel-Wahab Mohamed , Sandri Marcus , Holzhey David , Borger Michael , Ender Jörg , Ince Hüseyin , Öner Alper , Meyer-Saraei Roza , Hambrecht Rainer , Fach Andreas , Augenstein Thomas , Frey Norbert , König Inke R. , Vonthein Reinhard , Rückert Yvonne , Funkat Anne-Kathrin , Desch Steffen , Berggreen Astrid E. , Heringlake Matthias , de Waha-Thiele Suzanne ,   On behalf of the SOLVE-TAVI Investigators
Published: August 2020

Background:
In clinical practice, local anesthesia with conscious sedation (CS) is performed in roughly 50% of patients undergoing transcatheter aortic valve replacement. However, no randomized data assessing the safety and efficacy of CS versus general anesthesia (GA) are available.

Methods:
The SOLVE-TAVI (Comparison of Second-Generation Self-Expandable Versus Balloon-Expandable Valves and General Versus Local Anesthesia in Transcatheter Aortic Valve Implantation) trial is a multicenter, open-label, 2×2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement comparing CS versus GA. The primary efficacy end point was powered for equivalence (equivalence margin 10% with significance level 0.05) and consisted of the composite of all-cause mortality, stroke, myocardial infarction, infection requiring antibiotic treatment, and acute kidney injury at 30 days.

Results:

The primary composite end point occurred in 27.2% of CS and 26.4% of GA patients (rate difference, 0.8 [90% CI, −6.2 to 7.8];
P
equivalence
=0.015). Event rates for the individual components were as follows: all-cause mortality, 3.2% versus 2.3% (rate difference, 1.0 [90% CI, −2.9 to 4.8];
P
equivalence
<0.001); stroke, 2.4% versus 2.8% (rate difference, −0.4 [90% CI, −3.8 to 3.8];
P
equivalence
<0.001); myocardial infarction, 0.5% versus 0.0% (rate difference, 0.5 [90% CI, −3.0 to 3.9];
P
equivalence
<0.001), infection requiring antibiotics 21.1% versus 22.0% (rate difference, −0.9 [90% CI, −7.5 to 5.7];
P
equivalence
=0.011); acute kidney injury, 9.0% versus 9.2% (rate difference, −0.2 [90% CI, −5.2 to 4.8];
P
equivalence
=0.0005). There was a lower need for inotropes or vasopressors with CS (62.8%) versus GA (97.3%; rate difference, −34.4 [90% CI, −41.0 to −27.8]).

Conclusions:
Among patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement, use of CS compared with GA resulted in similar outcomes for the primary efficacy end point. These findings suggest that CS can be safely applied for transcatheter aortic valve replacement.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02737150.
Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction
Authors: Horiuchi Yu , Wettersten Nicholas , Patel Mitul P. , Mueller Christian , Neath Sean-Xavier , Christenson Robert H. , Morgenthaler Nils G. , McCord James , Nowak Richard M. , Vilke Gary M. , Daniels Lori B. , Hollander Judd E. , Apple Fred S. , Cannon Chad M. , Nagurney John T. , Schreiber Donald , deFilippi Christopher , Hogan Christopher , Diercks Deborah B. , Headden Gary , Limkakeng Alexander T. , Anand Inder , Wu Alan H.B. , Ebmeyer Stefan , Jaffe Allan S. , Peacock W. Frank , Maisel Alan 
Published: August 2020

Background:
The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers.

Methods:
Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated.

Results:

Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884,
P
=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI.

Conclusions:
Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.
Novel Mechanism of Microvesicle Regulation by the Antiviral Protein Tetherin During HIV Infection
Authors: Weber Emily A. , Singh Meera V. , Singh Vir B. , Jackson Joseph W. , Ture Sara K. , Suwunnakorn Sumanun , Morrell Craig N. , Maggirwar Sanjay B. 
Published: August 2020

Background
Microvesicles are cell membrane–derived vesicles that have been shown to augment inflammation. Specifically, monocyte‐derived microvesicles (MDMVs), which can express the coagulation protein tissue factor, contribute to thrombus formation and cardiovascular disease. People living with HIV experience higher prevalence of cardiovascular disease and also exhibit increased levels of plasma microvesicles. The process of microvesicle release has striking similarity to budding of enveloped viruses. The surface protein tetherin inhibits viral budding by physically tethering budding virus particles to cells. Hence, we investigated the role of tetherin in regulating the release of MDMVs during HIV infection.

Methods and Results
The plasma of aviremic HIV‐infected individuals had increased levels of tissue factor + MDMVs, as measured by flow cytometry, and correlated to reduced tetherin expression on monocytes. Superresolution confocal and electron microscopy showed that tetherin localized at the site of budding MDMVs. Mechanistic studies revealed that the exposure of monocytes to HIV‐encoded Tat triggered tetherin loss and subsequent rise in MDMV production. Overexpression of tetherin in monocytes led to morphologic changes in the pseudopodia directly underneath the MDMVs. Further, tetherin knockout mice demonstrated a higher number of circulating MDMVs and less time to bleeding cessation.

Conclusions
Our studies define a novel regulatory mechanism of MDMV release through tetherin and explore its contribution to the procoagulatory state that is frequently observed in people with HIV. Such insights could lead to improved therapies for individuals infected with HIV and also for those with cardiovascular disease.
Placental Mitochondria Therapy for Cerebral Ischemia-Reperfusion Injury in Mice
Authors: Nakamura Yoshihiko , Lo Eng H. , Hayakawa Kazuhide 
Published: August 2020

Background and Purpose:
There is an urgent need to develop adjunct therapies that can be added onto reperfusion for acute ischemic stroke. Recently, mitochondrial transplantation has emerged as a promising therapeutic approach for boosting brain tissue protection. In this proof-of-concept study, we investigate the feasibility of using placenta as a source for mitochondrial transplantation in a mouse model of transient focal cerebral ischemia-reperfusion.

Methods:
Mitochondria-enriched fractions were isolated from cryopreserved mouse placenta. Mitochondrial purity and JC1 membrane potentials were assessed by flow cytometry. Adenosine triphosphate and mitochondrial proteins were measured by luminescence intensity and western blot, respectively. Therapeutic efficacy of mitochondrial fractions was assessed in a mouse model of transient focal cerebral ischemia-reperfusion.

Results:
Flow cytometry analysis demonstrated that about 87% of placental mitochondria were viable and maintained JC1 membrane potentials after isolation. Placental mitochondrial fractions contained adenosine triphosphate equivalent to mitochondrial fractions isolated from skeletal muscle and brown fat tissue. Normalized mitochondrial antioxidant enzymes (glutathione reductase, MnSOD [manganese superoxide dismutase]) and HSP70 (heat shock protein 70) were highly preserved in placental mitochondrial fractions. Treatment with placental mitochondrial fractions immediately after reperfusion significantly decreased infarction after focal cerebral ischemia in mice.

Conclusions:
Cryopreserved placenta can be a feasible source for viable mitochondrial isolation. Transplantation with placental mitochondria may amplify beneficial effects of reperfusion in stroke.
Structure Functions and Structure Parameters of Velocity Fluctuations in Numerically Simulated Atmospheric Convective Boundary Layer Flows
Authors: Gibbs Jeremy A. , Fedorovich Evgeni 
Published: August 2020

AbstractWe extend our previous study, which dealt with structure functions of potential temperature fluctuations, and focus on the characteristics of second-order velocity structure functions and corresponding structure parameters in the atmospheric convective boundary layer. We consider the three previously reported methods to compute the structure parameters of turbulent velocity fields: the direct method, the true spectral method, and the approximate spectral method. The methods are evaluated using high-resolution gridded numerical data from large-eddy simulations of shear-free and shear-driven convective boundary layers. Results indicate that the direct and true spectral methods are more suitable than the approximate spectral method, which overestimates the structure parameters of velocity as a result of assuming the inertial-subrange shape of the velocity spectrum for all turbulence scales. Results also suggest that structure parameters of vertical velocity fluctuations are of limited utility because of violations of local isotropy, especially in shear-free convective boundary layers.
Multidecadal Warming and Density Loss in the Deep Weddell Sea, Antarctica
Authors: Strass Volker H. , Rohardt Gerd , Kanzow Torsten , Hoppema Mario , Boebel Olaf 
Published: August 2020

AbstractThe World Ocean is estimated to store more than 90% of the excess energy resulting from man-made greenhouse gas–driven radiative forcing as heat. Uncertainties of this estimate are related to undersampling of the subpolar and polar regions and of the depths below 2000 m. Here we present measurements from the Weddell Sea that cover the whole water column down to the sea floor, taken by the same accurate method at locations revisited every few years since 1989. Our results show widespread warming with similar long-term temperature trends below 700-m depth at all sampling sites. The mean heating rate below 2000 m exceeds that of the global ocean by a factor of about 5. Salinity tends to increase—in contrast to other Southern Ocean regions—at most sites and depths below 700 m, but nowhere strongly enough to fully compensate for the warming effect on seawater density, which hence shows a general decrease. In the top 700 m neither temperature nor salinity shows clear trends. A closer look at the vertical distribution of changes along an approximately zonal and a meridional section across the Weddell Gyre reveals that the strongest vertically coherent warming is observed at the flanks of the gyre over the deep continental slopes and at its northern edge where the gyre connects to the Antarctic Circumpolar Current (ACC). Most likely, the warming of the interior Weddell Sea is driven by changes of the Weddell Gyre strength and its interaction with the ACC.
COVID pandemic as an opportunity for improving mental health treatments of the homeless people
Authors: Martin Carmen , Andrés Pilar , Bullón Alberto , Villegas José Luis , de la Iglesia-Larrad Javier Ignacio , Bote Berta , Prieto Nieves , Roncero Carlos 
Published: August 2020

Background: Homeless population has been severely affected by the COVID-19 pandemic. Their living conditions, comorbidity with different pathologies and a greater frequency of mental disorders, make this population vulnerable. Method: We implemented a program of serial visits in a hostel for confined homeless of the city council social services, for the monitoring and treatment of mental disorders and substance abuse problems. Accompanied by serial phone and email contacts. Results: A highly significant percentage (63%) had mental disorders or substance abuse, requiring pharmacological intervention, and 37% began follow-up in resources of the Mental Health and Addiction network of the Psychiatric Service at the end of the program. Hospital emergency service visits were drastically reduced. None of them were infected with COVID-19. An individualized Social plan was drawn up in order to reintegrate them with support in the community. Conclusions: The Results have been really positive, meeting all the objectives and opening up developing new programs in the future, in the pandemic outbreak and out of it.
Building administrative capacity under developmental states in Chile and Singapore: a comparative perspective
Authors: Shamsul Haque M. , Puppim de Oliveira Jose A. 
Published: August 2020

Administrative capacity depends on the nature of the state of which the administrative system is an integral part. In recent years, there has been a revival of debates on the role of public administration under developmental states in Southeast Asia and Latin America. A major analytical component of developmental states has been their administrative capacity and how to build it. There are significant variations in administrative capacity among developmental states caused by divergences in their historical, economic, political, and cultural contexts. This article compares two cross-continental cases (Singapore and Chile) with regard to the formations of developmental states shaping their administrative systems and capacity-building initiatives. It examines the divergences in their state formations and the contextual factors affecting their administrative capacity. The article concludes by making some generalizations, offering an analytical framework for further research, and suggesting policies needed for building effective administrative capacity. Points for practitioners This article highlights the significance of administrative capacity-building for development. It explores how this capacity is shaped by the formation of the state under which public administration functions. In explaining this relationship between state formation and public administration, the article specifically focuses on the “developmental” state, compares two cross-continental cases (Singapore and Chile) as regards how these two developmental states differ and cause variations in their administrative systems, and explains the major contextual factors leading to such variations. This understanding is crucial to designing effective policies for building administrative capacity in any country depending on its state formation and context.
Clinical outcome of acute thoracic aortic syndrome in nonagenarians
Authors: Arakawa Mamoru , Okamura Homare , Miyagawa Atsushi , Kitada Yuichiro , Adachi Hideo 
Published: August 2020

Background Decision-making regarding the operability of thoracic aortic disease in nonagenarian patients remains controversial because outcomes of open surgical repair of the thoracic aorta are unclear. We investigated the surgical and nonsurgical outcomes of acute thoracic aortic syndrome treatment in nonagenarians. Methods After evaluating data in our institute from April 2016 to March 2020, we included 10 nonagenarians who needed surgical intervention on the thoracic aorta via a median sternotomy for acute thoracic aortic syndrome. The mean age of the cohort was 91.9 ± 2.1 years. Five patients underwent open surgical repair of the thoracic aorta (surgical group), and 5 refused surgery (nonsurgical group). All patients in the surgical group performed activities of daily living independently, with a mean clinical frailty scale of 3.2 ± 0.4. The surgical group included 4 patients with type A aortic dissection and one with a ruptured thoracic aortic aneurysm. Hemiarch replacement was performed in 3 patients and total arch replacement in 2. The mean follow-up period was 17.8 ± 5.1 months. Results Hospital mortality rates were 0% in the surgical and 80% in the nonsurgical group. The mean length of hospitalization was 28.4 ± 6.7 days in the surgical group. The 1-year survival rates were 100% in the surgical group and 20% in the nonsurgical group. Conclusion Open surgical repair for acute thoracic aortic syndrome via median sternotomy is a reasonable treatment option even in nonagenarians. Involvement of family members is important for decision-making to devise the optimal treatment strategy (surgical vs. medical).
Developing a fatigue programme: Protocol for the Nottingham Fatigue After Stroke (NotFAST2) study
Authors: Drummond Avril , Ablewhite Joanne , Condon Laura , Nair Roshan das , Jones Amanda , Jones Fiona , Sprigg Nikola , Thomas Shirley 
Published: August 2020

Introduction Post-stroke fatigue is common and is one of the most distressing symptoms after stroke. It has a negative impact on physical, social and psychological functioning; it is also associated with poor outcomes and increased mortality. The effective management of post-stroke fatigue is therefore regarded as a clinical priority. Method This study will use a mixed-methods design with three overlapping phases. Phase 1 will be a survey of existing fatigue management within the United Kingdom. In phase 2, interviews and focus groups will be conducted with stroke survivors with fatigue, carers and clinicians to determine strategies used to manage fatigue successfully. In phase 3, data from phases 1 and 2 will contribute to the co-design of a fatigue management programme with the NotFAST2 study Patient and Public Involvement group. This will be further refined through subsequent focus groups, which will include those with fatigue associated with other health conditions. Results Survey data will be analysed using descriptive statistics. Interview and focus group data will be analysed using a framework approach. Conclusion Post-stroke fatigue requires a comprehensive management programme necessitating input from key stakeholders. A post-stroke fatigue programme will be developed which will be tested in a future randomised controlled trial.