bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empagliflozin for Patients With Presumed Resistant Hypertension: A Post Hoc Analysis of the EMPA-REG OUTCOME Trial
Authors: Ferreira João Pedro , Fitchett David , Ofstad Anne Pernille , Kraus Bettina Johanna , Wanner Christoph , Zwiener Isabella , Zinman Bernard , Lauer Sabine , George Jyothis T , Rossignol Patrick , Zannad Faiez 
Published: April 2020

Abstract

BACKGROUND
Type 2 diabetes (T2D) and resistant hypertension often coexist, greatly increasing risk of target-organ damage and death. We explored the effects of empagliflozin in patients with and without presumed resistant hypertension (prHT) in a post hoc analysis of EMPA-REG OUTCOME (NCT01131676).

METHODS
Overall, 7,020 patients received empagliflozin 10, 25 mg, or placebo with median follow-up of 3.1 years. We defined baseline prHT as ≥3 classes of antihypertensive drugs including a diuretic and uncontrolled blood pressure (BP; systolic blood pressure (SBP) ≥140 and/or diastolic blood pressure ≥90 mm Hg) or ≥4 classes of antihypertensive, including a diuretic, and controlled BP. We explored the effect of empagliflozin on cardiovascular (CV) death, heart failure (HF) hospitalization, 3-point major adverse cardiac events, all-cause death, and incident/worsening nephropathy by Cox regression and BP over time by a mixed-repeated-measures-model analysis.

RESULTS
1,579 (22.5%) patients had prHT. The mean difference in change in SBP from baseline to week 12 vs. placebo was −4.5 (95% confidence interval, −5.9 to −3.1) mm Hg (P &lt; 0.001) in prHT and −3.7 (−4.5, −2.9) mm Hg (P &lt; 0.001) in patients without prHT. SBP was more frequently controlled (&lt;130/80 mm Hg) with empagliflozin than with placebo. Patients with prHT had 1.5- to 2-fold greater risk of HF hospitalization, incident/worsening nephropathy, and CV death compared with those without prHT. Empagliflozin improved all outcomes in patients with and without prHT (interaction P &gt; 0.1 for all outcomes).

CONCLUSIONS
Empagliflozin induced a clinically relevant reduction in SBP and consistently improved all outcomes regardless of prHT status. Due to these dual effects, empagliflozin should be considered for patients with hypertension and T2D.
RaacLogo: a new sequence logo generator by using reduced amino acid clusters
Authors: Zheng Lei , Liu Dongyang , Yang Wuritu , Yang Lei , Zuo Yongchun 
Published: April 2020

Abstract
Sequence logos give a fast and concise display in visualizing consensus sequence. Protein exhibits greater complexity and diversity than DNA, which usually affects the graphical representation of the logo. Reduced amino acids perform powerful ability for simplifying complexity of sequence alignment, which motivated us to establish RaacLogo. As a new sequence logo generator by using reduced amino acid alphabets, RaacLogo can easily generate many different simplified logos tailored to users by selecting various reduced amino acid alphabets that consisted of more than 40 clustering algorithms. This current web server provides 74 types of reduced amino acid alphabet, which were manually extracted to generate 673 reduced amino acid clusters (RAACs) for dealing with protein alignment. A two-dimensional selector was proposed for easily selecting desired RAACs with underlying biology knowledge. It is anticipated that the RaacLogo web server will play more high-potential roles for protein sequence alignment, topological estimation and protein design experiments. RaacLogo is freely available at http://bioinfor.imu.edu.cn/raaclogo.
Population history of the golden eagle inferred from whole-genome sequencing of three of its subspecies
Authors: Sato Yu , Ogden Rob , Kishida Takushi , Nakajima Nobuyoshi , Maeda Taku , Inoue-Murayama Miho 
Published: April 2020

AbstractThe application of evolutionary genetic research to investigate the potential for endangered species to adapt to changing environments is important for conservation biology. Effective population size (Ne) is informative for understanding adaptive potential as it refers to the genetic variation in breeding individuals who have contributed to contemporary and historic population diversity. We reconstruct fluctuations in Ne in three golden eagle subspecies (Japanese, Scottish, North American) using the pairwise sequential Markovian coalescent (PSMC) model based on whole-genome sequence data. Our results indicate the timing of subspeciation events and suggest significant ongoing demographic reductions since the start of the Last Glacial Period. Importantly, we find evidence for gene flow from continental populations into the ancestral Japanese population resulting in a short, sharp recovery in genetic diversity. Timing agrees with the palaeogeographic estimates of land bridge connections between the Japanese archipelago and Asian continent and matches a similar Ne spike in the Scottish population, but not in the North American population. Given contemporary declines in isolated Japanese and UK island populations, our study highlights a concerning loss of local genetic diversity, but also indicates the likely response of populations to genetic reinforcement from neighbouring subspecies, increasing management options and encouraging a range-wide species conservation approach.
A role of the frontotemporal lobar degeneration risk factor TMEM106B in myelination
Authors: Feng Tuancheng , Sheng Rory R , Solé-Domènech Santiago , Ullah Mohammed , Zhou Xiaolai , Mendoza Christina S , Enriquez Laura Camila Martinez , Katz Isabel Iscol , Paushter Daniel H , Sullivan Peter M , Wu Xiaochun , Maxfield Frederick R , Hu Fenghua 
Published: April 2020

Abstract
TMEM106B encodes a lysosomal membrane protein and was initially identified as a risk factor for frontotemporal lobar degeneration. Recently, a dominant D252N mutation in TMEM106B was shown to cause hypomyelinating leukodystrophy. However, how TMEM106B regulates myelination is still unclear. Here we show that TMEM106B is expressed and localized to the lysosome compartment in oligodendrocytes. TMEM106B deficiency in mice results in myelination defects with a significant reduction of protein levels of proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG), the membrane proteins found in the myelin sheath. The levels of many lysosome proteins are significantly decreased in the TMEM106B-deficient Oli-neu oligodendroglial precursor cell line. TMEM106B physically interacts with the lysosomal protease cathepsin D and is required to maintain proper cathepsin D levels in oligodendrocytes. Furthermore, we found that TMEM106B deficiency results in lysosome clustering in the perinuclear region and a decrease in lysosome exocytosis and cell surface PLP levels. Moreover, we found that the D252N mutation abolished lysosome enlargement and lysosome acidification induced by wild-type TMEM106B overexpression. Instead, it stimulates lysosome clustering near the nucleus as seen in TMEM106B-deficient cells. Our results support that TMEM106B regulates myelination through modulation of lysosome function in oligodendrocytes.
Coronavirus Disease 2019, Superinfections, and Antimicrobial Development: What Can We Expect?
Authors: Clancy Cornelius J , Nguyen M Hong 
Published: April 2020

AbstractCoronavirus disease 2019 (COVID-19) arose at a time of great concern about antimicrobial resistance (AMR). No studies have specifically assessed COVID-19–associated superinfections or AMR. Based on limited data from case series, it is reasonable to anticipate that an appreciable minority of patients with severe COVID-19 will develop superinfections, most commonly pneumonia due to nosocomial bacteria and Aspergillus. Microbiology and AMR patterns are likely to reflect institutional ecology. Broad-spectrum antimicrobial use is likely to be widespread among hospitalized patients, both as directed and empiric therapy. Stewardship will have a crucial role in limiting unnecessary antimicrobial use and AMR. Congressional COVID-19 relief bills are considering antimicrobial reimbursement reforms and antimicrobial subscription models, but it is unclear if these will be included in final legislation. Prospective studies on COVID-19 superinfections are needed, data from which can inform rational antimicrobial treatment and stewardship strategies, and models for market reform and sustainable drug development.
Olfactory and Gustatory Dysfunction in Coronavirus Disease 2019 (COVID-19)
Authors: Luers Jan C , Rokohl Alexander C , Loreck Niklas , Wawer Matos Philomena A , Augustin Max , Dewald Felix , Klein Florian , Lehmann Clara , Heindl Ludwig M 
Published: April 2020

Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide. Given scarce resources, nonlaboratory diagnostics are crucial. In this cross-sectional study, two-thirds of European patients with confirmed COVID-19 reported olfactory and gustatory dysfunction, indicating the significance of these symptoms in early diagnostics.
Dispute Settlement in the Belt and Road Initiative: Lessons from the Singapore Experience
Authors: Chong Justice Steven 
Published: April 2020

Abstract
Historically, Singapore has played an important role in the growth and success of the old maritime Silk Road. Today, Singapore remains an important stop on the Belt and Road, though its advantages now also lie in its position as a trusted, neutral forum for the efficient resolution of disputes as well as a platform for the sharing of ideas for the development of a legal framework for dispute resolution in the Belt and Road Initiative. Three initiatives have been taken by Singapore to strengthen its new position, including the Asian Business Law Institute, the Singapore International Commercial Court, and the Singapore–China Annual Legal and Judicial Roundtable.
The Effects of a Vocabulary Intervention on Teaching Multiple-Meaning Words to Students Who Are d/Deaf and Hard of Hearing
Authors: Alqraini Faisl M , Paul Peter V 
Published: April 2020

AbstractBuilding vocabulary knowledge, especially breadth and depth of word meanings, is a crucial step in assisting students to read and comprehend print independently. A large body of research has documented the low reading achievement levels of a number of Deaf and hard-of-hearing (DHH) students. The goal of the present study was to examine the effects of a vocabulary intervention to teach 24 multiple-meaning words to fourth-grade DHH students in Saudi Arabia by utilizing a single-case experimental design (multiple probe design across participants). A total of 5 students with a profound hearing loss participated in the study. About 3 of 5 received the intervention, whereas two other students served as an additional control component and were administered the pretest and posttest only. The data showed that there was a significant improvement in the recognition and comprehension scores of students who received the intervention. In contrast, students who did not receive the intervention showed no significant improvement on the posttest.
Pharmacological cancer treatment and venous thromboembolism risk
Authors: Muñoz Martín Andrés J , Ramírez Sara Pérez , Morán Laura Ortega , Zamorano Magdalena Ruiz , Benéitez María Carmen Viñuela , Salcedo Inmaculada Aparicio , Escobar Ignacio García , Fernández José Manuel Soria 
Published: April 2020

Abstract
Risk factors for cancer-associated thrombosis are commonly divided into three categories: patient-, cancer-, and treatment-related factors. Currently, different types of drugs are used in cancer treatment. Chemotherapy has been identified as an independent risk factor for venous thromboembolism (VTE). However, it should be noted, that the risk of VTE is not consistent among all cytotoxic agents. In addition, different supportive care drugs, such as erythropoiesis stimulating agents or granulocyte colony stimulating factors, and hormonotherapy have been associated to an increased risk of VTE. Immunotherapy and molecular-targeted therapies have significantly changed the treatment of cancer over the past decade. The main subtypes include tyrosine-kinase inhibitors, monoclonal antibodies, small molecules, and immunomodulatory agents. The relationship between VTE and targeted therapies remains largely unknown.
Bayesian network analysis of plasma microRNA sequencing data in patients with venous thrombosis
Authors: Thibord Florian , Munsch Gaëlle , Perret Claire , Suchon Pierre , Roux Maguelonne , Ibrahim-Kosta Manal , Goumidi Louisa , Deleuze Jean-François , Morange Pierre-Emmanuel , Trégouët David-Alexandre 
Published: April 2020

Abstract
MicroRNAs (miRNAs) are small regulatory RNAs participating to several biological processes and known to be involved in various pathologies. Measurable in body fluids, miRNAs have been proposed to serve as efficient biomarkers for diseases and/or associated traits. Here, we performed a next-generation-sequencing based profiling of plasma miRNAs in 344 patients with venous thrombosis (VT) and assessed the association of plasma miRNA levels with several haemostatic traits and the risk of VT recurrence. Among the most significant findings, we detected an association between hsa-miR-199b-3p and haematocrit levels (P = 0.0016), these two markers having both been independently reported to associate with VT risk. We also observed suggestive evidence for association of hsa-miR-370-3p (P = 0.019), hsa-miR-27b-3p (P = 0.016) and hsa-miR-222-3p (P = 0.049) with VT recurrence, the observations at the latter two miRNAs confirming the recent findings of Wang et al. Besides, by conducting Genome-Wide Association Studies on miRNA levels and meta-analyzing our results with some publicly available, we identified 21 new associations of single nucleotide polymorphisms with plasma miRNA levels at the statistical significance threshold of P &lt; 5 × 10−8, some of these associations pertaining to thrombosis associated mechanisms. In conclusion, this study provides novel data about the impact of miRNAs’ variability in haemostasis and new arguments supporting the association of few miRNAs with the risk of recurrence in patients with venous thrombosis.
Vegetation type determines spore deposition within a forest–agricultural mosaic landscape
Authors: Redondo Miguel A , Berlin Anna , Boberg Johanna , Oliva Jonàs 
Published: April 2020

ABSTRACTPredicting fungal community assembly is partly limited by our understanding of the factors driving the composition of deposited spores. We studied the relative contribution of vegetation, geographical distance, seasonality and weather to fungal spore deposition across three vegetation types. Active and passive spore traps were established in agricultural fields, deciduous forests and coniferous forests across a geographic gradient of ∼600 km. Active traps captured the spore community suspended in air, reflecting the potential deposition, whereas passive traps reflected realized deposition. Fungal species were identified by metabarcoding of the ITS2 region. The composition of spore communities captured by passive traps differed more between vegetation types than across regions separated by &gt;100 km, indicating that vegetation type was the strongest driver of composition of deposited spores. By contrast, vegetation contributed less to potential deposition, which followed a seasonal pattern. Within the same site, the spore communities captured by active traps differed from those captured by passive traps. Realized deposition tended to be dominated by spores of species related to vegetation. Temperature was negatively correlated with the fungal species richness of both potential and realized deposition. Our results indicate that vegetation may be able to maintain similar fungal communities across distances, and likely be the driving factor of fungal spore deposition at landscape level.
Drivers of Frailty from Adulthood into Old Age: Results from a 27-Year Longitudinal Population-Based Study in Sweden
Authors: Raymond Emma , Reynolds Chandra A , Dahl Aslan Anna K , Finkel Deborah , Ericsson Malin , Hägg Sara , Pedersen Nancy L , Jylhävä Juulia 
Published: April 2020

Abstract

Background
Frailty is a strong predictor of adverse outcomes. However, longitudinal drivers of frailty are not well understood. This study aimed at investigating the longitudinal trajectories of a frailty index (FI) from adulthood to late life and identifying the factors associated with the level and rate of change in FI.

Methods
An age-based latent growth curve analysis was performed in the Swedish Adoption/Twin Study of Aging (N = 1,842; aged 29–102 years) using data from up to 15 measurement waves across 27 years. A 42-item FI was used to measure frailty at each wave.

Results
A bilinear, two-slope model with a turning point at age 65 best described the age-related change in FI, showing that the increase in frailty was more than twice as fast after age 65. Underweight, obesity, female sex, overweight, being separated from one’s co-twin during childhood, smoking, poor social support, and low physical activity were associated with a higher FI at age 65, with underweight having the largest effect size. When tested as time-varying covariates, underweight and higher social support were associated with a steeper increase in FI before age 65, whereas overweight and obesity were associated with less steep increase in FI after age 65.

Conclusions
Factors associated with the level and rate of change in frailty are largely actionable and could provide targets for intervention. As deviations from normal weight showed the strongest associations with frailty, future public health programs could benefit from monitoring of individuals with abnormal BMI, especially those who are underweight.
Life Course Pathways From Childhood Socioeconomic Status to Later-Life Cognition: Evidence From the Wisconsin Longitudinal Study
Authors: Greenfield Emily A , Moorman Sara , Rieger Annika 
Published: April 2020

Abstract

Objectives
A growing body of research indicates that older adults are at greater risk for poorer cognition if they experienced low socioeconomic status (SES) as children. Guided by life course epidemiology, this study aimed to advance understanding of processes through which childhood SES influences cognition decades later, with attention to the role of scholastic performance in adolescence and SES in midlife.

Method
We used data from the Wisconsin Longitudinal Study (WLS), which has followed a cohort of high school graduates since they were 18 years old in 1957. Childhood SES was measured prospectively in adolescence, and measures of memory and language/executive functioning were based on neurocognitive assessments at age 72. We used participants’ scores on a statewide standardized test in high school as an indicator of scholastic performance in adolescence. The measure of SES in midlife included years of postsecondary education, income, and occupation status at age 53.

Results
Findings from structural equation models indicated that scholastic performance in adolescence and midlife status attainment together fully mediated associations between childhood SES and both memory and language/executive functioning at age 72. Adolescent scholastic performance was directly associated with later-life cognition, as well as indirectly through midlife status attainment.

Discussion
Findings provide support for both latency and social pathway processes when considering how SES in childhood influences later-life cognition. Results contribute to growing calls for social policies and programs to support optimal brain health at multiple phases throughout the life course, especially among individuals with lower SES as children.
Q values and wave inhomogeneity parameters of reflected inhomogeneous P and S waves at the free surface of an effective Biot solid
Authors: Liu Xu , Greenhalgh Stewart , Zhou Bing , Ren Zhengyong , Li Huijian 
Published: April 2020

SUMMARYIn this study, new methods are developed to estimate the dissipation factors, inhomogeneity parameters and phase velocities of the reflected waves at the free surface of a poro-viscoelastic solid in which the seismic wave propagation is described by effective Biot theory. The Christoffel equations of an effective Biot medium are solved for a general harmonic plane wave and the three complex velocities obtained corresponding to the shear wave (SV), fast-P wave and slow-P wave, together with their polarizations. Based on the complex form of the energy balance equation in an effective Biot material, expressions are derived for the energy ratios at the free surface. Moreover, the equations for the inhomogeneity parameters are derived as functions of the complex slowness or the unit polarization vectors. Based on the implicit and the explicit dissipation factor expressions, two methods are developed to obtain the dissipation factors, the inhomogeneity parameters and the phase velocities of mode-converted waves. These methods are illustrated by numerical examples which show that the dissipation factors, inhomogeneity parameters and phase velocities of reflected waves can strongly depend on the incidence angle (also reflected angle), the incident wave inhomogeneity parameter and the wave frequency. Ignoring these dependencies and using dissipation factors only valid for homogeneous waves can cause discrepancies in computed phase velocities and dissipation factors for interface generated (reflected/transmitted) inhomogeneous waves.