bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Death Among the First 80 543 Coronavirus Disease 2019 (COVID-19) Cases in China: Relationships Between Age, Underlying Disease, Case Severity, and Region
Authors: Zhang Yanping , Luo Wei , Li Qun , Wang Xijie , Chen Jin , Song Qinfeng , Tu Hong , Ren Ruiqi , Li Chao , Li Dan , Zhao Jing , McGoogan Jennifer M , Shan Duo , Li Bing , Zhang Jingxue , Dong Yanhui , Jin Yu , Mao Shuai , Qian Menbao , Lv Chao , Zhu Huihui , Wang Limin , Xiao Lin , Xu Juan , Yin Dapeng , Zhou Lei , Li Zhongjie , Shi Guoqing , Dong Xiaoping , Guan Xuhua , Gao George F , Wu Zunyou , Feng Zijian 
Published: May 2021

Abstract

Background
Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death.

Methods
A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses.

Results
Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78–23.33), presence of underlying disease (1.33; 1.19–1.49), worse case severity (severe: 3.86; 3.15–4.73; critical: 11.34; 9.22–13.95), and near-epicenter region (Hubei: 2.64; 2.11–3.30; Wuhan: 6.35; 5.04–8.00). CFR increased from 0.35% (30–39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%).

Conclusions
Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.
Predictive value of post-implantation frontal QRS-T angle in patients receiving cardiac resynchronization therapy
Authors: Gunduz R , Usalp S 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Objective
Favourable response criteria for cardiac resynchronization therapy (CRT) implantation are still under debate. We investigated the relationship between frontal QRS-Tangle and improvement of functional New York Heart Association (NYHA) class and thus favourable response to CRT.

Method
Eighty-one patients were included in the study who CRT implanted. ECG and echocardiography were obtained 1 week before and after six month-1 years the CRT procedure. Patients were classified as "NYHA improvement" and "NYHA non-improvement" according to their NYHA class. The frontal QRS-T angle was calculated the absolute value of the difference between the QRS and T wave axes [Frontal QRS-Tangle=(QRS axis-T axis)]

Results
The mean age of patients was 64.5 ± 9.1 years. There was no difference between two groups in terms of demographic features. The post-implantation LVEF was higher in patients NYHA improvement group (p &lt; 0.001). Post–implantation QRS duration (p = 0.008), cQT interval (p = 0.012), frontal QRS-T angle (p = 0.003) values were very shorter in NYHA improvement group (Table 1). In multivariate regression analysis showed the frontal QRS-T angle and age independent risk factors for improvement of NYHA class (p &lt; 0.05). The receiver operating characteristics curve analysis (ROC) were showed the optimal cut-off value of predicting NYHA improvement for frontal QRS-Tangle was &lt; 135 (AUC:0.69, 95%CI 0.575-0.814, p = 0.004). Conclusion: We found that after CRT implantation, functional NYHA class improvement was associated the shortened of QRS, cQT interval, increased LVEF and narrowed of the frontal QRS-Tangle (&lt;135 ms) was in both ischemic and non-ischemic patients Table 1 variables NYHA improvement group(43) NYHA non-improvement group (n = 34) p value age (years) 61.1 ± 9.9 66.5 ± 8.9 0.017 Post-implantation EF (%) 39 (30-50) 30 (20-37) &lt;0.001 Pre-CRT Frontal QRS-T angle (º) 153.0 ± 57.8 155.7 ± 56.7 0.840 Post-CRT Frontal QRS-T angle (º) 118.4 ± 69.7 168.1 ± 67.8 0.003 Table 1
Late HIV diagnosis among immigrants in Spain vs. native-born Spaniards, 2010–15
Authors: Gogishvili Megi , Huang Terry T -K , Costa Sergio A , Florez Karen , Mateu-Gelabert Pedro , Valls Maria R A , Rivero María , Saumoy Maria , Samperiz Gloria , Cervero Miguel , Pulido Federico , Pérez José A ,   Cohort of the Spanish AIDs Research Network
Published: May 2021

Abstract

Background
In 2012, the central government of Spain enacted Royal Decree-Law (RDL) 16/2012 and Royal Decree (RD) 1192/2012, which abolished universal healthcare coverage, thus limiting access to care for undocumented immigrants. Free health care was also no longer granted to anyone who has never been employed. In this context, this study investigated the prevalence of late HIV diagnoses (LHDs) among immigrants living in Spain vs. native-born Spaniards.

Methods
Data (n = 5943) from the 2010 to 2015 Cohort of the Spanish AIDs Research Network were used, including HIV-positive and antiretroviral therapy (ART)-naïve patients throughout Spain. Multivariate logistic models were fitted to compare the prevalence of LHD among the groups, adjusting for covariates.

Results
The prevalence of LHD in the total sample was 39.5%. Compared with native-born Spaniards (n = 4445), immigrants (n = 1488) were more likely to have LHD (37.4% vs. 45.7%, respectively; P &lt; 0.001). Multivariate analysis showed that the prevalence ratio of LHD among immigrants vs. native-born Spaniards was 1.15 [95% confidence interval (CI), 1.02–1.28], after adjusting for covariates. This disparity widened from 2010 to 2011 (APR = 1.14, 95% CI, 1.02–1.29) to 2012–15 (APR = 1.28, 95% CI, 1.17–1.39), although the change was not statistically significant.

Conclusions
Immigrants in Spain had a higher risk of LHD compared with native-born counterparts. LHD is an important healthcare marker due to the positive benefits of early HIV diagnosis, including prevention, improvements in health outcomes and decreases in overall cost of treatment. More research is needed on the causes of the disparity and potential social and policy interventions to reduce the prevalence of LHD among immigrants.
Characterizing dopaminergic neuron vulnerability using genome-wide analysis
Authors: Davis Jacinta , Da Silva Santos Claire , Zavala Narda Caudillo , Gans Nicholas , Patracuolla Daniel , Fehrenbach Monica , Babcock Daniel T 
Published: May 2021

Abstract
Parkinson’s disease (PD) is primarily characterized by the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. To identify genes that are associated with DA neuron loss, we screened through 201 wild-caught populations of Drosophila melanogaster as part of the Drosophila Genetic Reference Panel. Here, we identify the top-associated genes containing single-nucleotide polymorphisms that render DA neurons vulnerable. These genes were further analyzed by using mutant analysis and tissue-specific knockdown for functional validation. We found that this loss of DA neurons caused progressive locomotor dysfunction in mutants and gene knockdown analysis. The identification of genes associated with the progressive loss of DA neurons should help to uncover factors that render these neurons vulnerable in PD, and possibly develop strategies to make these neurons more resilient.
Thermal conductivity of granitoids of varying composition up to 300 °C and implications for crustal thermal models
Authors: Ray Labani , Chopra Nishu , Hiloidari Sikha , Naidu N Narsimha , Kumar Varun 
Published: May 2021

SUMMARY
A thermal conductivity profile through the upper crustal column is an essential ingredient in any thermal modelling. Granitoid is one of the major constituents of the upper crust in the Archaean cratons. Although granitoids have a wide range in composition, yet data on their thermal conductivity at elevated temperatures are very limited. At present, a single value is commonly used to characterize the decrease in thermal conductivity with temperature for the upper crust. We are reporting thermal conductivity measured at 25 °C, 50 °C and thereafter at 50 °C intervals up to 300 °C on 34 granitoid samples of four compositionally different types. The samples are alkali granite, biotite granite, granodiorite and metasomatised granodiorite from one of the Archaean cratons of the Indian shield, known as Bundelkhand Craton. Before studying the samples at elevated temperatures, these have been studied for their physical, petrological and geochemical characteristics. By 300 °C, the thermal conductivity decreases on the average by 28–31 per cent for metasomatised granodiorite, alkali granite and biotite granite, and in stark contrast by 16 per cent for granodiorite. Expressing the thermal conductivity variation with temperature as λT = λRT (1 + bT)–1, two distinct temperature coefficient (b) values have been found, 1.1 × 10–3 to 2.2 × 10–3 K–1 for alkali feldspar granite to monzogranite and 0.4 × 10–3 to 1.2 × 10–3 K–1 for granodiorite to tonalite to quartz diorite. One of the implications of this outcome is illustrated by applying these two distinct temperature coefficients for the upper crust for a 1-D generic model with a surface heat flow and appropriate radiogenic heat production of the crustal column in arriving at crustal temperature–depth profiles. The temperature differences at the base of a 40-km crust vary as much as 90 °C. Further, the temperature coefficient can be expressed as b = 0.71 × λRT– 0.63 for the alkali feldspar granite to monzogranite, whereas b = 0.83 × λRT– 1.26 for the granodiorite to tonalite to quartz diorite, which will be useful in determining the temperature coefficient of various types of granitoid from thermal conductivity at room temperature (λRT).
Rapid finite-frequency microseismic noise source inversion at regional to global scales
Authors: Igel Jonas K H , Ermert Laura A , Fichtner Andreas 
Published: May 2021

SUMMARY
Ambient noise cross-correlations can be used as self-consistent observables, opening novel possibilities for investigating ambient noise sources. To optimize the forward-modelling of global ambient noise cross-correlations for any given distribution of noise sources in the microseismic frequency range up to 0.2 Hz, we implement (i) pre-computed wavefields and (ii) spatially variable grids. This enables rapid inversions for microseismic noise sources based on finite-frequency source sensitivity kernels. We use this advancement to perform regional and global gradient-based iterative inversions of the logarithmic energy ratio in the causal and acausal branches of microseismic noise cross-correlations. Synthetic inversions show promising results, with good recovery of the main dominant noise sources of the target model. Data inversions for several consecutive days at the beginning of October 2019 demonstrate the capability of inverting for the spatio-temporal variations of the sources of secondary microseisms in the ocean. This paves the way for daily ambient noise source inversions which could help improve full-waveform ambient noise tomography and subsurface monitoring methods.
PAK1 inhibition reduces tumor size and extends the lifespan of mice in a genetically engineered mouse model of Neurofibromatosis Type 2 (NF2)
Authors: Hawley Eric , Gehlhausen Jeffrey , Karchugina Sofiia , Chow Hoi-Yee , Araiza-Olivera Daniela , Radu Maria , Smith Abbi , Burks Ciersten , Jiang Li , Li Xiaohong , Bessler Waylan , Masters Andrea , Edwards Donna , Burgin Callie , Jones David , Yates Charles , Clapp D Wade , Chernoff Jonathan , Park Su-Jung 
Published: May 2021

Abstract
Neurofibromatosis Type II (NF2) is an autosomal dominant cancer predisposition syndrome in which germline haploinsufficiency at the NF2 gene confers a greatly increased propensity for tumor development arising from tissues of neural crest derived origin. NF2 encodes the tumor suppressor, Merlin, and its biochemical function is incompletely understood. One well-established function of Merlin is as a negative regulator of group A serine/threonine p21-activated kinases (PAKs). In these studies we explore the role of PAK1 and its closely related paralog, PAK2, both pharmacologically and genetically, in Merlin-deficient Schwann cells and in a genetically engineered mouse model (GEMM) that develops spontaneous vestibular and spinal schwannomas. We demonstrate that PAK1 and PAK2 are both hyper activated in Merlin-deficient murine schwannomas. In preclinical trials, a pan Group A PAK inhibitor, FRAX-1036, transiently reduced PAK1 and PAK2 phosphorylation in vitro, but had insignificant efficacy in vivo. NVS-PAK1-1, a PAK1 selective inhibitor, had a greater but still minimal effect on our GEMM phenotype. However, genetic ablation of Pak1 but not Pak2 reduced tumor formation in our NF2 GEMM. Moreover, germline genetic deletion of Pak1 was well tolerated, while conditional deletion of Pak2 in Schwann cells resulted in significant morbidity and mortality. These data support the further development of PAK1-specific small molecule inhibitors and the therapeutic targeting of PAK1 in vestibular schwannomas and argue against PAK1 and PAK2 existing as functionally redundant protein isoforms in Schwann cells.
Small molecule 1a reduces FMRpolyG-mediated toxicity in in vitro and in vivo models for FMR1 premutation
Authors: Haify Saif N , Buijsen Ronald A M , Verwegen Lucas , Severijnen Lies-Anne W F M , de Boer Helen , Boumeester Valerie , Monshouwer Roos , Yang Wang-Yong , Cameron Michael D , Willemsen Rob , Disney Matthew D , Hukema Renate K 
Published: May 2021

Abstract
Fragile X-associated tremor and ataxia syndrome (FXTAS) is a late-onset, progressive neurodegenerative disorder characterized by tremors, ataxia and neuropsychological problems. This disease is quite common in the general population with approximately 20 million carriers worldwide. The risk of developing FXTAS increases dramatically with age, with about 45% of male carriers over the age of 50 being affected. FXTAS is caused by a CGG-repeat expansion (CGGexp) in the fragile X mental retardation 1 (FMR1) gene. CGGexp RNA is translated into the FMRpolyG protein by a mechanism called RAN translation. Although both gene and pathogenic trigger are known, no therapeutic interventions are available at this moment. Here, we present, for the first time, primary hippocampal neurons derived from the ubiquitous inducible mouse model which is used as a screening tool for targeted interventions. A promising candidate is the repeat binding, RAN translation blocking, small molecule 1a. Small molecule 1a shields the disease-causing CGGexp from being translated into the toxic FMRpolyG protein. Primary hippocampal neurons formed FMRpolyG-positive inclusions, and upon treatment with 1a, the numbers of FMRpolyG-positive inclusions are reduced. We also describe for the first time the formation of FMRpolyG-positive inclusions in the liver of this mouse model. Treatment with 1a reduced the insoluble FMRpolyG protein fraction in the liver but not the number of inclusions. Moreover, 1a treatment had a reducing effect on the number of Rad23b-positive inclusions and insoluble Rad23b protein levels. These data suggest that targeted small molecule therapy is effective in an FXTAS mouse model and has the potential to treat CGGexp-mediated diseases, including FXTAS.
BORCS6 is involved in the enlargement of lung lamellar bodies in Lrrk2 knockout mice
Authors: Araki Miho , Ito Kyohei , Takatori Sho , Ito Genta , Tomita Taisuke 
Published: May 2021

Abstract
Leucine-rich repeat kinase 2 (LRRK2) has been implicated in the pathogenesis of Parkinson disease. It has been shown that Lrrk2 knockout (KO) rodents have enlarged lamellar bodies (LBs) in their alveolar epithelial type II cells, although the underlying mechanisms remain unclear. Here we performed proteomic analyses on LBs isolated from Lrrk2 KO mice and found that the LB proteome is substantially different in Lrrk2 KO mice compared with wild-type mice. In Lrrk2 KO LBs, several Rab proteins were increased, and subunit proteins of BLOC-1-related complex (BORC) were decreased. The amount of surfactant protein C was significantly decreased in the bronchoalveolar lavage fluid obtained from Lrrk2 KO mice, suggesting that LB exocytosis is impaired in Lrrk2 KO mice. We also found that the enlargement of LBs is recapitulated in A549 cells upon KO of LRRK2 or by treating cells with LRRK2 inhibitors. Using this model, we show that KO of BORCS6, a BORC subunit gene, but not other BORC genes, causes LB enlargement. Our findings implicate the LRRK2-BORCS6 pathway in the maintenance of LB morphology.
Achieving Histologic Normalization in Ulcerative Colitis Is Associated With a Reduced Risk of Subsequent Dysplasia
Authors: Shaffer Seth R , Erondu Amarachi I , Traboulsi Cindy , Rai Victoria , Krugliak Cleveland Noa , Israel Amanda , Christensen Britt , Rubin David T 
Published: May 2021

Abstract

Background
Complete histologic normalization is associated with improved clinical outcomes in ulcerative colitis (UC). However, it is currently unknown what effect achieving histologic normalization has on the development of dysplasia.

Methods
We performed a retrospective analysis of 495 patients with a confirmed diagnosis of UC from a tertiary center. Patients were categorized according to the best histologic assessment they had during their disease course: histologic normalization, histologic quiescence, or persistent histologic activity. We assessed dysplasia rates in these patient groups after achieving histologic normalization or histologic quiescence, or 8 years after UC diagnosis in those with persistent histologic activity. Kaplan-Meier graphs and Cox regression analyses were performed to estimate this effect.

Results
The incidence rate of dysplasia development after achieving histologic normalization was statistically significantly less when compared with the incidence rate after achieving histologic quiescence (P = 0.001) and in those with persistent histologic activity 8 years after UC diagnosis (P = 0.033). In multivariate analysis, at any point throughout UC duration, dysplasia development was statistically lower in those with histologic normalization (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.13-0.81) but not in those with histologic quiescence (aHR, 0.52; 95% CI, 0.25-1.10), compared with those with persistent histologic inflammation. When assessing the time after achieving histologic normalization, histologic quiescence, or 8 years post UC diagnosis in those with persistent histologic activity, we found that patients with histologic normalization had a subsequent decreased risk of developing dysplasia (aHR, 0.09; 95% CI, 0.01-0.72), compared with patients without normalization.

Conclusions
Histologic normalization is associated with a decreased risk in patients with UC of developing subsequent dysplasia, compared with patients without histologic normalization. These findings have implications for surveillance intervals.
University Experiences of Marine Science Research and Outreach Beyond the Classroom
Authors: Sims Randi J , Tallapragada Meghnaa , Payton Tokea G , Noonan Kara , Prosser Kathy L , Childress Michael J 
Published: May 2021

Synopsis
Climate and ocean literacy are two of the most important challenges facing society today. However, many students lack exposure to these topics upon entering college. As a result, these students must rely on learning climate literacy and ocean conservation through experiences outside of those provided in the traditional undergraduate classroom. To fill this gap, we initiated a marine science professional development program to expose undergraduate students to ocean literacy principles and climate change concepts through marine ecology research and educational outreach. This study evaluates the effects of our undergraduate experiential learning for individuals involved in our research team, our educational outreach team, or both. Clemson University alumni that participated in our program were surveyed to determine educational and professional gains in three areas related to: (1) knowledge; (2) careers; and (3) attitudes. Multiple linear and logistic regressions were used to understand the relationships between gains and program type, mentor experience, and duration of program enrollment. In addition, we evaluated demographic covariates including age, ideology, and gender. Our study found that perceived knowledge of marine science and science communication skills increased with positive mentor experience. Alumni that rated their experience with their mentors highly also indicated that the program was important to their careers after graduation. Students who participated in any program for a prolonged period were more likely to indicate that marine science was important to their careers. These students were also more likely to continue their education. Additionally, we saw that a sense of belonging and identity in science, as well as the understanding of climate change threat on the marine environment, all increased with longer program involvement, more than the type of experience (research versus outreach). Overall, we found that both the research and outreach programs offered opportunities for advancements in knowledge, careers, and attitudes. These results provide evidence that experiential learning has the potential to increase student engagement and understanding of climate change and ocean literacy communication as well as a sense of belonging in science-oriented fields.
Controllability of fractional neutral functional differential equations with infinite delay driven by fractional Brownian motion
Authors: Dieye Moustapha , Lakhel El Hassan , McKibben Mark A 
Published: May 2021

Abstract
In this work, we establish a controllability result for a class of fractional neutral stochastic functional differential equations with infinite delay driven by fractional Brownian motion. To attain our objective we adapt the argument of Lakhel & McKibben (2018, Stochastics 90, no. 3, 313–329) where the existence of mild solutions to such stochastic equations was studied. An example is provided to show the applicability of the theoretical result.
Finite-volume approximation of the invariant measure of a viscous stochastic scalar conservation law
Authors: Boyaval Sébastien , Martel Sofiane , Reygner Julien 
Published: May 2021

Abstract
We study the numerical approximation of the invariant measure of a viscous scalar conservation law, one-dimensional and periodic in the space variable and stochastically forced with a white-in-time but spatially correlated noise. The flux function is assumed to be locally Lipschitz continuous and to have at most polynomial growth. The numerical scheme we employ discretizes the stochastic partial differential equation (SPDE) according to a finite-volume method in space and a split-step backward Euler method in time. As a first result, we prove the well posedness as well as the existence and uniqueness of an invariant measure for both the semidiscrete and the split-step scheme. Our main result is then the convergence of the invariant measures of the discrete approximations, as the space and time steps go to zero, towards the invariant measure of the SPDE, with respect to the second-order Wasserstein distance. We investigate rates of convergence theoretically, in the case where the flux function is globally Lipschitz continuous with a small Lipschitz constant, and numerically for the Burgers equation.