bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant non-existence of sequences in genomes and proteomes
Authors: Koulouras Grigorios , Frith Martin C 
Published: February 2021

AbstractMinimal absent words (MAWs) are minimal-length oligomers absent from a genome or proteome. Although some artificially synthesized MAWs have deleterious effects, there is still a lack of a strategy for the classification of non-occurring sequences as potentially malicious or benign. In this work, by using Markovian models with multiple-testing correction, we reveal significant absent oligomers, which are statistically expected to exist. This suggests that their absence is due to negative selection. We survey genomes and proteomes covering the diversity of life and find thousands of significant absent sequences. Common significant MAWs are often mono- or dinucleotide tracts, or palindromic. Significant viral MAWs are often restriction sites and may indicate unknown restriction motifs. Surprisingly, significant mammal genome MAWs are often present, but rare, in other mammals, suggesting that they are suppressed but not completely forbidden. Significant human MAWs are frequently present in prokaryotes, suggesting immune function, but rarely present in human viruses, indicating viral mimicry of the host. More than one-fourth of human proteins are one substitution away from containing a significant MAW, with the majority of replacements being predicted harmful. We provide a web-based, interactive database of significant MAWs across genomes and proteomes.
Regulation of RNA editing by intracellular acidification
Authors: Malik Turnee N , Doherty Erin E , Gaded Vandana M , Hill Theodore M , Beal Peter A , Emeson Ronald B 
Published: February 2021

AbstractThe hydrolytic deamination of adenosine-to-inosine (A-to-I) by RNA editing is a widespread post-transcriptional modification catalyzed by the adenosine deaminase acting on RNA (ADAR) family of proteins. ADAR-mediated RNA editing modulates cellular pathways involved in innate immunity, RNA splicing, RNA interference, and protein recoding, and has been investigated as a strategy for therapeutic intervention of genetic disorders. Despite advances in basic and translational research, the mechanisms regulating RNA editing are poorly understood. Though several trans-acting regulators of editing have been shown to modulate ADAR protein expression, previous studies have not identified factors that modulate ADAR catalytic activity. Here, we show that RNA editing increases upon intracellular acidification, and that these effects are predominantly explained by both enhanced ADAR base-flipping and deamination rate at acidic pH. We also show that the extent of RNA editing increases with the reduction in pH associated with conditions of cellular hypoxia.
Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study
Authors: Nangaku Masaomi , Kondo Kazuoki , Ueta Kiichiro , Kokado Yoshimasa , Kaneko Genki , Matsuda Hiroki , Kawaguchi Yutaka , Komatsu Yasuhiro 
Published: February 2021

Abstract

Background
Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis.

Methods
The efficacy and safety of vadadustat, compared with darbepoetin alfa, was determined in a Phase 3 double-blind study in Japanese anemic patients on hemodialysis. Patients receiving erythropoiesis-stimulating agents (ESAs) were randomized and switched to either vadadustat or darbepoetin alfa for 52 weeks. Doses were adjusted to maintain a hemoglobin (Hb) level of 10.0–12.0 g/dL. The primary endpoint was average Hb level at Weeks 20 and 24.

Results
Of the 323 randomized patients, 120 and 135 completed the 52-week treatment period in the vadadustat and darbepoetin alfa groups, respectively. The average Hb levels at Weeks 20 and 24 [least square mean (LSM) and 95% confidence interval (CI)] were 10.61 (10.45–10.76) and 10.65 (10.50–10.80) g/dL in the vadadustat and darbepoetin alfa groups, respectively, demonstrating vadadustat’s noninferiority to darbepoetin alfa (difference: −0.05 g/dL; 95% CI −0.26 to 0.17). In both groups, the mean Hb levels were maintained within the target range for 52 weeks. Furthermore, irrespective of patient backgrounds, the LSMs of Hb at Week 52 were within the target range. The most common adverse events were nasopharyngitis, diarrhea and shunt stenosis, which occurred at similar frequencies in both groups. No new safety concerns were identified.

Conclusions
Vadadustat was as well-tolerated and effective as darbepoetin alfa in maintaining Hb levels within the target range. The findings suggest that vadadustat can be an alternative to ESA in the management of anemia in Japanese hemodialysis patients receiving ESA (ClinicalTrials.gov, NCT03439137).
Changes in Medicare Physician Reimbursement for Stroke Procedures from 2000 to 2019
Authors: Pines Andrew R , Haglin Jack M , Demaerschalk Bart M 
Published: February 2021

ABSTRACT

BACKGROUND
There is limited data regarding financial trends for procedural reimbursement in stroke care. A comprehensive understanding of such trends is important as continued progress is made to advance agreeable reimbursement models in the care of stroke patients.

OBJECTIVE
To evaluate monetary trends in Medicare reimbursement rates for commonly utilized procedures in stroke care from 2000 to 2019.

METHODS
The Centers for Medicare & Medicaid Services was queried for the included Current Procedural Terminology (CPT) codes and reimbursement data were extracted. The CPT codes compiled were the most commonly performed procedures for stroke-related International Classification of Diseases (ICD)-10 codes at our institution (I60-I63). Additionally, data were collected for alteplase and telestroke codes. The rate of change between procedures was compared utilizing an unpaired Student's t-test. All monetary data were adjusted for inflation to 2019 US dollars utilizing the US Consumer Price Index.

RESULTS
After adjusting for inflation, the average reimbursement for stroke (ICD I60-I63) procedures decreased by 11.2% from 2000 to 2019 (average of −0.43% per year). The adjusted reimbursement rate for included telestroke codes decreased by 12.1% from 2010 to 2019 (average of −1.4% per year). From 2005 to 2019, the reimbursement for alteplase rose by 163.98% (average of +7.3% per year).

CONCLUSION
When adjusted for inflation, Medicare reimbursement for common stroke procedures has decreased from 2000 to 2019. In contrast, reimbursement for alteplase has increased markedly. It is important to be aware of these trends in order to contextualize healthcare economic analyses and inform discussions.
The magnetic effect on a strongly correlated system with two currents near the quantum critical point from holography
Authors: Lee Jaeha , Sin Sang-Jin , Song Geunho 
Published: February 2021

Abstract
We study the magnetic effect in a strongly interacting system with two conserved currents near the quantum critical point (QCP). For this purpose, we introduce the hyper-scaling violation geometry with the black hole. Considering the perturbation near the background geometry, we compute the transport coefficients using holographic methods. We calculated the magneto-transport for general QCP and discuss the special point $(z,\theta)=(3/2,1)$, where the data of Dirac material have previously been well described.
Work Readiness of New Graduate Physical Therapists for Private Practice in Australia: Academic Faculty, Employer, and Graduate Perspectives
Authors: Wells Cherie , Olson Rebecca , Bialocerkowski Andrea , Carroll Sara , Chipchase Lucy , Reubenson Alan , Scarvell Jennie Mary , Kent Fiona 
Published: February 2021

Abstract

Objective
The purpose of this study is to explore academic faculty, employer, and recent graduate perspectives of the work readiness of Australian new graduate physical therapists for private practice and factors that influence new graduate preparation and transition to private practice.

Methods
This study used a mixed-methods design with 3 surveys and 12 focus groups. A total of 112 participants completed a survey, and 52 participated in focus groups. Descriptive statistics were used to summarize the quantitative data, and thematic analysis was used to analyze the qualitative data. Triangulation across participant groups and data sources was undertaken.

Results
Australian new graduate physical therapists were perceived to be “somewhat ready” for private practice and “ready” by their third year of employment. Participants proposed that new graduates bring enthusiasm, readiness to learn, and contemporary, research-informed knowledge. New graduates were also perceived to find autonomous clinical reasoning and timely caseload management difficult; to have limited business, marketing, and administration knowledge and skills; and to present with underdeveloped confidence, communication, and interpersonal skills. Factors perceived to influence graduate transition included private practice experience, such as clinical placements and employment; employer and client expectations of graduate capabilities; workplace support; university academic preparation and continuing education; and individual graduate attributes and skills.

Conclusion
Australian new graduate physical therapists have strengths and limitations in relation to clinical, business, and employability knowledge and skills. New graduate work readiness and transition may be enhanced by additional private practice experience, employer and client expectation management, provision of workplace support, and tailored university and continuing education.

Impact
The number of new graduate physical therapists employed in private practice in Australia is increasing; however, until this study, their work readiness for this setting was unknown. This exploration of new graduate performance in private practice and transition can help to increase understanding and enhancement of work-readiness.
Implementation and Evaluation of the Virtual Graded Repetitive Arm Supplementary Program (GRASP) for Individuals With Stroke During the COVID-19 Pandemic and Beyond
Authors: Yang Chieh-ling , Waterson Seonaid , Eng Janice J 
Published: February 2021

Abstract

Objective
Given the uncertainty of the coronavirus disease 2019 (COVID-19) pandemic, implementing telerehabilitation that enables the remote delivery of rehabilitation services is needed to mitigate the spread of COVID-19. We studied the implementation and the effectiveness of the virtual Graded Repetitive Arm Supplementary Program (GRASP) delivered and evaluated via videoconferencing in individuals with stroke.

Methods
The Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework with mixed methods was used to evaluate the implementation of the 2 iterations of the program delivered by a nonprofit organization during the pandemic.

Results
Reach: Seventeen people were screened, 13 people were eligible, and 11 consented to participate in the study. Effectiveness: Between baseline and posttest, participants with stroke demonstrated significant improvement in upper extremity function (Arm Capacity and Movement Test) and self-perceived upper extremity (UE) function (Stroke Impact Scale). Adoption: Factors that facilitate program uptake by the staff were well-planned implementation, appropriate screening procedure, and helpful feedback from the audits. All staff felt comfortable using videoconferencing technology to deliver the program despite some technical difficulties. Factors contributing to ongoing participation included that the participants liked the group, they perceived improvements, and the instructor was encouraging. Only one participant with stroke was not comfortable using the videoconferencing technology. Implementation: The program was implemented as intended as evaluated by a fidelity checklist. Participants’ adherence was high, as verified by the average attendance and practice time. Maintenance: The organization continued to offer the program.

Conclusion
The virtual GRASP program was successfully implemented. Although the program was effective in improving both measured and perceived UE function in a small sample of individuals with stroke, caution should be taken in generalizing the results.

Impact
Implementing telerehabilitation is crucial to optimize patient outcomes and reduce the spread of COVID-19. Our findings provide guidance on the process of delivering a UE rehabilitation program remotely via videoconferencing for stroke. Moreover, insights that arise from this study also inform the implementation of other telerehabilitation services.
Why Precarious Work Is Bad for Health: Social Marginality as Key Mechanisms in a Multi-National Context
Authors: Macmillan Ross , Shanahan Michael J 
Published: February 2021

AbstractThe expansion of precarious work in recent decades has motivated a large body of research on its implications for health. While considerable work has focused on whether precarious work undermines health, much less is known about why it matters. To fill this gap, this paper offers and tests a conceptual model whereby the effects of precarious work on health are mediated by social marginality, specifically reduced self-efficacy, weaker social integration, and lower social capital. All three mechanisms are understood as both social consequences of precarious work and important determinants of health. Empirically, we use data from the European Social Survey and investigate (1) conditional direct effects of precarious work on self-rated health and (2) extent of mediation via the three mechanisms. Furthermore, we assess the generalizability of the model across five welfare state regimes that prior work has deemed to be important moderators of the health–precarious work relationship. Results indicate precarious work has significant conditional direct effects and indirect effects through all three mediators that significantly reduce effect of precarious work on health. This is robust in the general sample and for four of five welfare state regimes. These findings highlight a previously unexplored vector connecting precarious work to health and indicate that the effects of precarious work on perceptions of self and social relations is a key link to poorer health. The study also expands conceptualization of the broad role of socioeconomic status for health inequalities and furthers understanding of the mechanisms at work.
It’s a Family (Policy) Affair: Family Policies and Heterogeneity in Gender Attitudes
Authors: Jozwiak Andreas 
Published: February 2021

AbstractWhy do younger cohorts in advanced democracies hold more conservative gender attitudes? Rather than understanding these attitudes as a “backlash,” I argue that these represent mixes of traditional and egalitarian attitudes that ultimately reflect the gendered character of family policies. Using an original dataset of family policies, I show that policies which alleviate care burdens and encourage workforce participation of mothers are related to support for working mothers. Conversely, policies which reinforce traditional divisions of labor are linked to greaterprevalence of essentialist beliefs. Different combinations of family policies cross-pressure gender attitudes, resulting in complex groupings, or “varieties of egalitarianism.”
The Effects of Fatty Acids on Brain Microglia Immune Responses
Authors: Lowry Jessica R. , Klegeris Andis 
Published: February 2021

BACKGROUNDIn 2018, the estimated global cost of health care for patients with dementia is expected to be over 1 trillion dollars (United States currency). Dementia in many cases is caused by Alzheimer's disease (AD), for which no viable treatment currently exists. Some significant risks in the development of AD are preventable, including diet‐related factors. One important diet‐related factor, dietary fats, is involved in key cellular processes. However, there is limited research on the role of dietary fats in the regulation of inflammation within the central nervous system (CNS). Non‐neuronal cells called microglia regulate the immune status of the CNS, and their dysregulated responses can lead to the enhanced release of cytotoxic mediators. These microglia‐released mediators can cause extensive neuron death, which is observed in AD. Metabolites of alpha‐linolenic acid (ALA) and linoleic acid (LA) are well‐known for modulating peripheral and CNS inflammation. However, the effects of ALA and LA on microglia are unknown.OBJECTIVESAssess whether ALA and LA affect microglial immune responses.METHODSBV‐2 microglia cells were treated with ALA or LA for 24 h, followed by pro‐inflammatory stimulation with bacterial lipopolysaccharide (LPS) for 24 h. Microglial supernatants and total protein from lysed BV‐2 cells were collected. The supernatants were used to quantify the secretion of reactive nitrogen species (RNS) by BV‐2 cells. Proteins were used to quantify the production of inducible nitric oxide synthase (iNOS) by western blotting.RESULTSBoth ALA and LA significantly reduced RNS secretion by LPS‐stimulated BV‐2 microglia. LA, but not ALA, significantly reduced iNOS levels in LPS‐stimulated microglia. Data were analyzed using the randomized block design analysis of variance (ANOVA), followed by Dunnett's post‐hoc test.CONCLUSIONSDietary fatty acids can modulate select microglial immune responses, and should be further investigated for their roles in CNS inflammation, which is involved in the progression of AD.Support or Funding InformationNatural Sciences and Engineering Research Council, The Jack Brown and Family Alzheimer's Disease Research FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Interleukin‐10 in Type 1 Diabetes‐induced bone loss in mice
Authors: Rios‐Arce Naiomy Deliz , Mohr Susanne , Coughlin Brandon A. , Feenstra Derrick , Christian Barbara , McCabe Laura R. , Parameswaran Narayanan 
Published: February 2021

The prevalence of diabetes is increasing worldwide. In addition to the commonly known complications of this disease, it is well known that Type 1 diabetes (T1D) can have a detrimental effect on bone health. Studies have shown that during the disease onset there is an increase in systemic and local cytokine production, suggesting that cytokines could play a regulatory role in bone loss during diabetes. Role of the anti‐inflammatory interleukin 10 (IL‐10) in bone physiology is well known. However, the role of IL‐10 in bone health during short‐ and long‐term diabetes has not been studied. We hypothesized that deficiency of IL‐10 in mice will lead to exacerbated bone loss in T1D. To test this, IL‐10 knockout and the corresponding C57BL/6J wild‐type mice (males, 7 weeks of age) were subjected to streptozotocin (STZ) injection (65 mg/g body weight) for 5 days to induce T1D. Diabetes was confirmed two weeks after the first injection by a blood glucose level of >300 mg/dL. Bones were collected at 4 weeks (short‐term) and 12 weeks (long‐term) post‐diabetes induction. Bone volume fractions (BVF) of femur and vertebrae were analyzed using microcomputed tomography (μCT) system. As expected T1D induced significant trabecular bone loss in WT mice at both 4 and 12 weeks after induction (BVF @ 4 weeks: WT control 29% VS WT STZ 15.9%; @12 weeks: WT control: 34.6% VS WT STZ: 9.6%; n=8–10). However, deficiency of IL‐10 exacerbated bone loss at the 4‐week time point (BVF @ 4 weeks WT STZ: 15.9% VS KO STZ: 8.7%; n=7), but by 12 weeks T1D BVF did not differ from WT mice. Vertebrae showed similar phenotype. We further found that cortical bone was affected in a comparable manner. Bone effects corresponded to changes in osteoblast RNA markers but not osteoclast RNA markers, suggesting that IL‐10 primarily affects anabolic events in the T1D bone. Taken together, these results suggest that IL‐10 is required for osteoblast regulation during early diabetes‐induced bone loss.Support or Funding InformationR01 DK101050 03R01 AT007695 04
Tinnitus and 3-Year Change in Audiometric Hearing Thresholds
Authors: Curhan Sharon G. , Halpin Christopher , Wang Molin , Eavey Roland D. , Curhan Gary C. 
Published: February 2021

Objectives:
Tinnitus and hearing loss commonly coexist, however, the temporal relation between tinnitus and hearing loss is complex and not fully understood. Our objective was to examine the longitudinal association between persistent tinnitus, bothersome tinnitus, and 3-year elevation of audiometric hearing thresholds.

Design:
We conducted a longitudinal cohort study among 3106 women (mean age 59 years) who were participants in the Nurses’ Health Study II (2012–2018). Information on tinnitus was obtained from biennial questionnaires. Longitudinal changes in air conduction thresholds (0.5 to 8 kHz) were assessed by pure-tone audiometry conducted by licensed audiologists at 19 audiology testing sites across the United States. Logistic regression was used to estimate multivariable-adjusted odds ratios (MVORs, 95% confidence interval [CI]) and evaluate the relations of persistent tinnitus (several days per week or more), bothersome tinnitus (interferes with work, sleep, or daily activities), and risk of 3-year elevation of hearing thresholds.

Results:
Persistent tinnitus was associated with higher risk of 3-year elevation of hearing thresholds across a broad range of frequencies. Compared with women without tinnitus, the MVORs (95% CI) for ≥5-dB threshold elevation among women with persistent tinnitus were 1.01 (0.81, 1.25) at 0.5 kHz, 1.45 (1.17, 1.81) at 1 kHz, 1.25 (1.00, 1.56) at 2 kHz, 1.34 (1.07, 1.69) at 3 kHz, 1.34 (1.06, 1.70) at 4 kHz, 1.49 (1.16, 1.91) at 6 kHz, and 1.63 (1.25, 2.12) at 8 kHz. The magnitudes of the associations for ≥10-dB threshold elevation were similar. The magnitudes of the associations were substantially greater among women with bothersome tinnitus. For example, compared with women without tinnitus, the MVORs (95% CI) for a ≥5- and ≥10-dB elevation of hearing thresholds at 4 kHz were 2.97 (1.50, 5.89) and 2.79 (1.38, 5.65), respectively. The risk was elevated even among women with tinnitus who had clinically normal hearing thresholds at baseline. In analyses that examined the association of tinnitus and elevation of low-, mid- and high-frequency pure-tone average (PTA) hearing thresholds, the results were similar. Compared with women without tinnitus, the MVORs (95% CI) for ≥5-dB PTA elevation among women with persistent tinnitus were 1.29 (0.99,1.67) for LPTA(0.5,1,2 kHz); 1.44 (1.16, 1.78) for MPTA(3,4 kHz); and 1.38 (1.11, 1.71) for HPTA(6,8 kHz). For ≥10-dB elevation, the MVORs were 2.85 (1.55, 5.23), 1.52 (1.10, 2.09), and 1.41 (1.10, 1.82), respectively.

Conclusion:
Persistent tinnitus was associated with substantially higher risk of 3-year hearing threshold elevation, even among women with clinically normal baseline hearing. The magnitudes of the associations were greater among those with bothersome tinnitus. Monitoring hearing sensitivities may be indicated in patients with tinnitus, including those without audiometric evidence of hearing impairment.