bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease
Authors: Okada Yuki , Uehara Shinichiro , Shibata Mikiko , Koh Hideo , Oue Keiko , Kambe Hiroshi , Morimoto Michio , Sato Kyoko Kogawa , Hayashi Tomoshige 
Published: June 2019

<b><i>Background:</i></b> Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD. <b><i>Methods:</i></b> A prospective cohort study of 9,116 middle-aged nondiabetic ­Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate &#x3c;60 mL/min/1.73 m<sup>2</sup>. We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1–23.0 g ethanol/day), moderate drinkers (23.1–46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis. <b><i>Results:</i></b> During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11–1.70), 1.58 (95% CI 1.28–1.95), 2.27 (95% CI 1.86–2.77), and 3.12 (95% CI 2.56–3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46–0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD. <b><i>Conclusions:</i></b> Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD.
Targeted Deletion of Hepatocyte
Abca1
Increases Plasma HDL (High-Density Lipoprotein) Reverse Cholesterol Transport via the LDL (Low-Density Lipoprotein) Receptor
Authors: Bashore Alexander C. , Liu Mingxia , Key Chia-Chi C. , Boudyguina Elena , Wang Xianfeng , Carroll Caitlin M. , Sawyer Janet K. , Mullick Adam E. , Lee Richard G. , Macauley Shannon L. , Parks John S. 
Published: June 2019

Objective:
The role of hepatocyte Abca1 (ATP binding cassette transporter A1) in trafficking hepatic free cholesterol (FC) into plasma versus bile for reverse cholesterol transport (RCT) is poorly understood. We hypothesized that hepatocyte Abca1 recycles plasma HDL-C (high-density lipoprotein cholesterol) taken up by the liver back into plasma, maintaining the plasma HDL-C pool, and decreasing HDL-mediated RCT into feces.

Approach and Results:

Chow-fed hepatocyte-specific
Abca1
knockout (HSKO) and control mice were injected with human HDL radiolabeled with
125
I-tyramine cellobiose (
125
I-TC; protein) and
3
H-cholesteryl oleate (
3
H-CO).
125
I-TC and
3
H-CO plasma decay, plasma HDL
3
H-CO selective clearance (ie,
3
H-
125
I fractional catabolic rate), liver radiolabel uptake, and fecal
3
H-sterol were significantly greater in HSKO versus control mice, supporting increased plasma HDL RCT. Twenty-four hours after
3
H-CO-HDL injection, HSKO mice had reduced total hepatic
3
H-FC (ie,
3
H-CO hydrolyzed to
3
H-FC in liver) resecretion into plasma, demonstrating Abca1 recycled HDL-derived hepatic
3
H-FC back into plasma. Despite similar liver LDLr (low-density lipoprotein receptor) expression between genotypes, HSKO mice treated with LDLr-targeting versus control antisense oligonucleotide had slower plasma
3
H-CO-HDL decay, reduced selective
3
H-CO clearance, and decreased fecal
3
H-sterol excretion that was indistinguishable from control mice. Increased RCT in HSKO mice was selective for
3
H-CO-HDL, since macrophage RCT was similar between genotypes.

Conclusions:
Hepatocyte Abca1 deletion unmasks a novel and selective FC trafficking pathway that requires LDLr expression, accelerating plasma HDL-selective CE uptake by the liver and promoting HDL RCT into feces, consequently reducing HDL-derived hepatic FC recycling into plasma.
MARK4 (Microtubule Affinity-Regulating Kinase 4)-Dependent Inflammasome Activation Promotes Atherosclerosis—Brief Report
Authors: Clement Marc , Chen Xiao , Chenoweth Hannah L. , Teng Zhongzhao , Thome Sarah , Newland Stephen A. , Harrison James , Yu Xian , Finigan Alison J. , Mallat Ziad , Li Xuan 
Published: June 2019

Objective:
MARK4 (microtubule affinity-regulating kinase 4) regulates NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3) inflammasome activation. The aim of the study is to examine the role of MARK4 in hematopoietic cells during atherosclerosis.

Methods and Results:

We show increased MARK4 expression in human atherosclerotic lesions compared with adjacent areas. MARK4 is coexpressed with NLRP3, and they colocalize in areas enriched in CD68-positive but α-SMA (α-smooth muscle actin)–negative cells. Expression of MARK4 and NLRP3 in the atherosclerotic lesions is associated with the production of active IL (interleukin)-1β and IL-18. To directly assess the role of hematopoietic MARK4 in NLRP3 inflammasome activation and atherosclerotic plaque formation,
Ldlr
(low-density lipoprotein receptor)-deficient mice were lethally irradiated and reconstituted with either wild-type or
Mark4
-deficient bone marrow cells, and were subsequently fed a high-fat diet and cholesterol diet for 9 weeks.
Mark4
deficiency in bone marrow cells led to a significant reduction of lesion size, together with decreased circulating levels of IL-18 and IFN-γ (interferon-γ). Furthermore,
Mark4
deficiency in primary murine bone marrow–derived macrophages prevented cholesterol crystal–induced NLRP3 inflammasome activation, as revealed by reduced caspase-1 activity together with reduced production of IL-1β and IL-18.

Conclusions:
MARK4-dependent NLRP3 inflammasome activation in the hematopoietic cells regulates the development of atherosclerosis.
Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke
Authors: Deng Yiming , Chen Duanduan , Wang Luyao , Gao Feng , Jin Bo , Lv Hong , Zhang Guojun , Sun Xuan , Liu Lian , Mo Dapeng , Ma Ning , Song Ligang , Huo Xiaochuan , Yan Tianyi , Miao Zhongrong 
Published: June 2019

Background and Purpose—
Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown. In the current study, for the first time, we investigated the role of long noncoding RNA Nespas in ischemic stroke.

Methods—
We used in vivo models of middle cerebral artery occlusion and in vitro models of oxygen-glucose deprivation to illustrate the effect of long noncoding RNA Nespas on ischemic stroke.

Results—
We found expression of Nespas was significantly increased in ischemic cerebral tissues and oxygen-glucose deprivation–treated BV2 cells in a time-dependent manner. Silencing of Nespas aggravated middle cerebral artery occlusion operation–induced IR injury and cell death. In addition, proinflammatory cytokine production and NF-κB (nuclear factor-κB) signaling activation were inhibited by Nespas overexpression. TAK1 (transforming growth factor-β–activated kinase 1) was found to directly interact with Nespas, and TAK1 activation was significantly suppressed by Nespas. At last, we found Nespas-inhibited TRIM8 (tripartite motif 8)-induced K63-linked polyubiquitination of TAK1.

Conclusions—
We showed that Nespas played anti-inflammatory and antiapoptotic roles in cultured microglial cells after oxygen-glucose deprivation stimulation and in mice after ischemic stroke by inhibiting TRIM8-related K63-linked polyubiquitination of TAK1.
Preliminary investigation of antimicrobial activity of the skin secretions of frogs from Bangladesh
Authors: Islam Md. Sirajul , Rahman Md. Mokhlesur , Rahaman Md. Mizanur 
Published: June 2019

Abstract
Amphibians, like some animals and plants, defend themselves against various pathogenic organisms by producing and secreting various peptides and small molecules from granular skin glands. In this study, we evaluated for the first time, the antibiotic activity of the skin secretions of 8 different frog species (Euphlyctis cyanophlyctis, E. hexadactylus, Fejervarya teraiensis, F. asmati, F. syhadrensis, Hoplobatrachus tigerinus, Microhyla ornata and Polypedates leucomystax) from Bangladesh. These secretions were collected by a nonlethal approach through chemical stimulation and the antibacterial activity was evaluated by broth macrodilution method against some Gram-positive and Gram-negative bacteria. Our study revealed that all the skin secretions (8 out of 8) from the selected frogs have antimicrobial activity against Gram-positive bacteria and 7 out of 8 skin secretions possess antibacterial activity against Gram-negative bacteria tested. Further analysis of data showed that these secretions are significantly more effective against Gram-positive bacteria than Gram-negative bacteria.
CMIP5 Models’ Ability to Capture Observed Trends under the Influence of Shifts and Persistence: An In-Depth Study on the Colorado River Basin
Authors: Tamaddun Kazi Ali , Kalra Ajay , Kumar Sanjiv , Ahmad Sajjad 
Published: June 2019

AbstractThis study evaluated the ability of phase 5 of the Coupled Model Intercomparison Project (CMIP5) to capture observed trends under the influence of shifts and persistence in their data distributions. A total of 41 temperature and 25 precipitation CMIP5 simulation models across 22 grid cells (2.5° × 2.5° squares) within the Colorado River basin were analyzed and compared with the Climate Research Unit Time Series (CRU-TS) observed datasets over a study period of 104 years (from 1901 to 2004). Both the modeled simulations and observations were tested for shifts, and the time series before and after the shifts were analyzed separately for trend detection and quantification. Effects of several types of persistence were accounted for prior to both the trend and shift detection tests. The mean significant shift points (SPs) of the CMIP5 temperature models across the grid cells were found to be within a narrower range (between 1957 and 1968) relative to the CRU-TS observed SPs (between 1924 and 1985). Precipitation time series, especially the CRU-TS dataset, had a lack of significant SPs, which led to an inconsistency between the models and observations since the number of grid cells with a significant SP was not comparable. The CMIP5 temperature trends, under the influence of shifts and persistence, were able to match the observed trends very satisfactorily (within the same order of magnitude and consistent direction). Unlike the temperature models, the CMIP5 precipitation models detected SPs that were earlier than the observed SPs found in the CRU-TS data. The direction (as well as the magnitude) of trends, before and after significant shifts, was found to be inconsistent between the modeled simulations and observed precipitation data. Shifts, based on their direction, were found either to strengthen or to neutralize the preexisting trends in both the model simulations and the observations. The results also suggest that the temperature and precipitation data distributions were sensitive to different types of persistence—such sensitivity was found to be consistent between the modeled and observed datasets. The study detected certain biases in the CMIP5 models in detecting the SPs (tendency of detecting shifts earlier for precipitation and later for temperature than the observed shifts) and also in quantifying the trends (overestimating the trend slopes)—such insights may be helpful in evaluating the efficacy of the simulation models in capturing observed trends under uncertainties and natural variabilities.
Assessment of Climatology and Predictability of Mid-Atlantic Tropical Cyclone Landfalls in a High-Atmospheric-Resolution Seasonal Prediction System
Authors: Manganello Julia V. , Cash Benjamin A. , Swenson Erik T. , Kinter III James L. 
Published: June 2019

AbstractTropical cyclone (TC) landfalls over the U.S. mid-Atlantic region, which include the so-called Sandy-like, or westward-curving, tracks, are among the most infrequent landfalls along the U.S. East Coast. However, when these events do occur, the resulting economic and societal consequences can be devastating. A recent example is Hurricane Sandy in 2012. Multimodel ensemble seasonal hindcasts conducted with a high-atmospheric-resolution coupled prediction system based on the ECMWF operational model (Project Minerva) are used here to compile the statistics of these rare events. Minerva hindcasts are found to exhibit skill in reproducing climatological characteristics of the mid-Atlantic TC landfalls particularly at the highest atmospheric horizontal spectral resolution of T1279 (16-km grid spacing). Historical forecasts are further interrogated to identify regional and large-scale environmental conditions associated with these rare TC tracks to better quantify their predictability on synoptic time scales, and their dependence on model resolution. Evolution of the large-scale atmospheric flow patterns leading to mid-Atlantic TC landfalls is analyzed using local finite-amplitude wave activity (LWA). We have identified large-amplitude quasi-stationary features in the LWA and sea surface temperature (SST) anomaly distributions that persist up to about a week leading to these land-falling events. A statistical model utilizing indices based on the LWA and SST anomalies as predictors is developed that exhibits skill (mostly at T1279) in predicting mid-Atlantic TC landfalls several days in advance. Implications of these results for longer time-scale predictions of mid-Atlantic TC landfalls including climate change projections are discussed.
Preparing for Doris: Exploring Public Responses to Impact-Based Weather Warnings in the United Kingdom
Authors: Taylor Andrea L. , Kause Astrid , Summers Barbara , Harrowsmith Melanie 
Published: June 2019

Abstract
In the United Kingdom, the Met Office issues regionally calibrated impact-based weather warnings. These aim to reduce harm to people and property. To decrease risk from severe weather, it is important to understand how members of the U.K. public interpret and act on these warnings. This paper addresses this through a postevent survey (n = 552) conducted following Storm Doris, a 2017 winter storm during which wind warnings were issued across much of the United Kingdom. Survey questions examined 1) understanding of impact-based wind warnings, 2) interpretation of local warning level, 3) predictors of perceived local risk (likelihood, impact severity, concern) implied by warnings, 4) predictors of trust in the forecast, and 5) predictors of recalled and anticipated action. Our findings indicate that U.K. residents generally understand that weather warnings are based on potential weather impacts, although many do not realize warnings are regionally calibrated. We also find that while local warning levels are rarely underestimated, they may sometimes be overestimated. Institutional trust in the Met Office and perceived vulnerability to weather predict both perceived risk and behavioral response, while warning “understandability” is linked to greater trust in the forecast. Strikingly, while differences in local warning levels influenced risk perception, they did not affect recalled or intended behavioral response. This study highlights the importance of institutional trust in the effective communication of severe weather warnings, and a need for education on impact-based weather warnings. Above all, it demonstrates the need for further exploration of the effect of weather warnings on protective behavior.
New local treatment for photoaging using a formulation containing piroxicam 0.8% and sunscreen
Authors: Mazzeo Mauro , Diluvio Laura , Di Prete Monia , Mazzilli Sara , Garofalo Virginia , Coniglione Filadelfo , Orlandi Augusto , Bianchi Luca , Campione Elena 
Published: June 2019

Objective Skin aging is a complex process influenced by several factors that cause DNA damage and alter the extracellular matrix. The anti-inflammatory drug piroxicam can counteract photocarcinogenesis and photoaging by blocking cyclooxygenases-1 and 2, matrix metalloproteinases, and ornithine decarboxylase, and inducing apoptosis. Methods We conducted an open observational study in 50 adults with moderate to severe signs of photoaging treated with a new local formulation of piroxicam 0.8% plus sunscreen for 16 weeks. Photoaging was assessed using a validated dermoscopic photoaging scale. Each patient’s own perception of their skin quality was assessed using a graphic scale. Results The new formulation demonstrated a reliable effect on photoaging after 16 weeks, based on improved median dermoscopic photoaging and skin-quality scores. No patients experienced any adverse effects. Conclusions To the best of our knowledge, this study provides the first evidence for the safe and effective use of a local piroxicam formulation for the treatment of moderate to severe photoaging.
Periventricular magnetisation transfer ratio abnormalities in multiple sclerosis improve after alemtuzumab
Authors: Brown J William L , Prados Carrasco Ferran , Eshaghi Arman , Sudre Carole H , Button Tom , Pardini Matteo , Samson Rebecca S , Ourselin Sebastien , Wheeler-Kingshott Claudia AM Gandini , Jones Joanne L , Coles Alasdair J , Chard Declan T 
Published: June 2019

Background: In multiple sclerosis (MS), disease effects on magnetisation transfer ratio (MTR) increase towards the ventricles. This periventricular gradient is evident shortly after first symptoms and is independent of white matter lesions. Objective: To explore if alemtuzumab, a peripherally acting disease-modifying treatment, modifies the gradient’s evolution, and whether baseline gradients predict on-treatment relapses. Methods: Thirty-four people with relapsing-remitting MS underwent annual magnetic resonance imaging (MRI) scanning (19 receiving alemtuzumab (four scans each), 15 untreated (three scans each)). The normal-appearing white matter was segmented into concentric bands. Gradients were measured over the three bands nearest the ventricles. Mixed-effects models adjusted for age, gender, relapse rate, lesion number and brain parenchymal fraction compared the groups’ baseline gradients and evolution. Results: Untreated, the mean MTR gradient increased (+0.030 pu/band/year) but decreased following alemtuzumab (−0.045 pu/band/year, p = 0.037). Within the alemtuzumab group, there were no significant differences in baseline lesion number ( p = 0.568) nor brain parenchymal fraction ( p = 0.187) between those who relapsed within 4 years ( n = 4) and those who did not ( n = 15). However, the baseline gradient was significantly different ( p = 0.020). Conclusion: Untreated, abnormal periventricular gradients worsen with time, but appear reversible with peripheral immunotherapy. Baseline gradients – but not lesion loads or brain volumes – may predict on-treatment relapses. Larger confirmatory studies are required.
Alarming attitudinal barriers to help-seeking in drug-related emergency situations: Results from a Swedish online survey
Authors: Soussan Christophe , Kjellgren Anette 
Published: June 2019

Background: New troublesome drug trends constitute a challenge for public health. Sweden has the second highest drug-related mortality rate in Europe. This calls for an investigation into the help-seeking attitudes of young adults to early middle-aged individuals asking how they would act in acute drug-related emergency or overdose situations. Methods: In total, 1232 individuals completed an online survey promoted on Sweden’s largest discussion forum Flashback.org . Their free-text responses were analysed according to inductively generated categories. Results: Around 60% of the sample would act as expected and contact emergency care without hesitation. However, approximately 32% of the sample showed palpable resistance and would put off seeking help and use emergency care only as a last resort due to, for example, fear of legal repercussions and stigma. Moreover, 8% displayed a total lack of confidence in public healthcare and would avoid it at all costs or entirely disregard it as an option due to the alleged risk of negative consequences and experienced restrictions on their personal freedom. Conclusions: While the inevitable criminalisation and stigmatisation associated with Sweden’s “zero tolerance” drug policy putatively serve as deterrents to drug use, our results demonstrate that these measures may also contribute to attitudes which discourage help-seeking. Such attitudes may at least partly explain the growing and comparatively high number of drug-induced deaths. Therefore, attitudinal and structural barriers to acute help-seeking in drug-related emergency situations should be acknowledged and investigated further in order to minimise harm.
Reducing burnout, vicarious trauma, and secondary traumatic stress through investigating purpose in life in social workers
Authors: Singer Jonathan , Cummings Caroline , Moody Sarah A , Benuto Lorraine T 
Published: June 2019

Summary Social workers fulfill vital roles, servicing clients from vulnerable populations and maintaining their welfare. As a result of frequent interaction with clients who have often experienced trauma, these workers are susceptible to experiencing burnout, secondary traumatic stress, and vicarious trauma. This study aimed to identify if purpose in life is a protective factor for adult/elder protective services (AEPS) and child protective services (CPS) workers. A comprehensive search of AEPS and CPS agencies resulted in more than 500 agencies throughout the United States. Three multiple regressions were run, with purpose in life as the independent variable, controlling for social workers’ years of experience, ethnicity, average of number of hours worked per week. Findings A sample of 292 participants ranging in age from 18 to 58 years of age, with a mean age of 42.03(12.34), participated in this study. Of the 292 social workers, 126 reported being CPS workers and 166 reported being AEPS workers. In all three linear regressions, higher purpose in life resulted in lower rates of vicarious trauma ( F(3, 263)=10.364, p<.001), secondary traumatic stress ( F(3, 263)=16.548, p<.001), and burnout ( F(3, 263)= 23.912, p<.001) when controlling for number of hours worked per week and years of experience. The amount of variance explained by these models ranged from 11 to 21%. Post hoc correlations between study variables were conducted, including the association between purpose in life and CS. Applications This study provides evidence necessary to warrant an intervention for protective services workers, specifically targeted toward increasing purpose in life.