bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of adenine-mutagenesis in diversity-generating retroelements
Authors: Handa Sumit , Reyna Andres , Wiryaman Timothy , Ghosh Partho 
Published: December 2020

AbstractDiversity-generating retroelements (DGRs) vary protein sequences to the greatest extent known in the natural world. These elements are encoded by constituents of the human microbiome and the microbial ‘dark matter’. Variation occurs through adenine-mutagenesis, in which genetic information in RNA is reverse transcribed faithfully to cDNA for all template bases but adenine. We investigated the determinants of adenine-mutagenesis in the prototypical Bordetella bacteriophage DGR through an in vitro system composed of the reverse transcriptase bRT, Avd protein, and a specific RNA. We found that the catalytic efficiency for correct incorporation during reverse transcription by the bRT-Avd complex was strikingly low for all template bases, with the lowest occurring for adenine. Misincorporation across a template adenine was only somewhat lower in efficiency than correct incorporation. We found that the C6, but not the N1 or C2, purine substituent was a key determinant of adenine-mutagenesis. bRT-Avd was insensitive to the C6 amine of adenine but recognized the C6 carbonyl of guanine. We also identified two bRT amino acids predicted to nonspecifically contact incoming dNTPs, R74 and I181, as promoters of adenine-mutagenesis. Our results suggest that the overall low catalytic efficiency of bRT-Avd is intimately tied to its ability to carry out adenine-mutagenesis.
Association between implementation of novel therapies and improved survival in patients starting haemodialysis: the Swedish Renal Registry 2006–15
Authors: Evans Marie , Xu Hong , Rydell Helena , Prütz Karl-Göran , Lindholm Bengt , Stendahl Maria , Segelmark Mårten , Carrero Juan-Jesus 
Published: December 2020

AbstractBackgroundThe recent years have witnessed significant therapeutic advances for patients on haemodialysis (HD). We evaluated temporal changes in treatments practices and survival rates among incident HD patients.MethodsThis was an observational study of patients initiating HD in Sweden in 2006–15. Trends of HD-related practices, medications and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACEs) across calendar years were compared against the age- and sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks.ResultsAmong 6612 patients, age and sex were similar, but the burden of comorbidities increased over time. The proportion of patients receiving treatment by haemodiafiltration, ≥3 sessions/week, lower ultrafiltration rate and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006–07 to 11.1% in 2014–15. The risk of death decreased by 6% [hazard ratio (HR) = 0.94, 95% confidence interval (CI) 0.90–0.99] every 2 years, and the risk of MACE by 4% (HR = 0.96, 95% CI 0.92–1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR = 1.00, 95% CI 0.92–1.09 for death and 1.00, 0.94–1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher in 2006–07 [standardized incidence rate ratio (sIRR) = 6.0, 95% CI 5.3–6.9] to 5.6 higher in 2014–15 (sIRR = 5.57, 95% CI 4.8–6.4).ConclusionsGradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among HD patients.
Clinical events and patient-reported outcome measures during CKD progression: findings from the Chronic Renal Insufficiency Cohort Study
Authors: Grams Morgan E , Surapaneni Aditya , Appel Lawrence J , Lash James P , Hsu Jesse , Diamantidis Clarissa J , Rosas Sylvia E , Fink Jeffrey C , Scialla Julia J , Sondheimer James , Hsu Chi-Yuan , Cheung Alfred K , Jaar Bernard G , Navaneethan Sankar , Cohen Debbie L , Schrauben Sarah , Xie Dawei , Rao Pandu , Feldman Harold I ,   the CRIC study investigators, Go Alan S , He Jiang , Rahman Mahboob , Townsend Raymond R 
Published: December 2020

Abstract

Background
Patients with chronic kidney disease (CKD) face risks of not only end-stage kidney disease (ESKD), cardiovascular disease (CVD) and death, but also decline in kidney function, quality of life (QOL) and mental and physical well-being. This study describes the multidimensional trajectories of CKD using clinical events, kidney function and patient-reported outcome measures (PROMs). We hypothesized that more advanced CKD stages would associate with more rapid decline in each outcome.

Methods
Among 3939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, we evaluated multidimensional disease trajectories by G- and A-stages of enrollment estimated glomerular filtration rate (eGFR) and albuminuria, respectively. These trajectories included clinical events (ESKD, CVD, heart failure and death), eGFR decline and PROMs [kidney disease QOL (KDQOL) burden, effects and symptoms questionnaires, as well as the 12-item short form mental and physical component summaries]. We also evaluated a group-based multitrajectory model to group participants on the basis of longitudinal PROMs and compared group assignments by enrollment G- and A-stage.

Results
The mean participant age was 58 years, 45% were women, mean baseline eGFR was 44 mL/min/1.73 m2 and median urine albumin:creatinine ratio was 52 mg/g. The incidence of all clinical events was greater and eGFR decline was faster with more advanced G- and A-stages. While baseline KDQOL and physical component measures were lower with more advanced G- and A-stage of CKD, changes in PROMs were inconsistently related to the baseline CKD stage. Groups formed on PROM trajectories were fairly distinct from existing CKD staging (observed agreement 60.6%) and were associated with the risk of ESKD, CVD, heart failure and death.

Conclusions
More advanced baseline CKD stage was associated with a higher risk of clinical events and faster eGFR decline, and was only weakly related to changes in patient-reported metrics over time.
Dementia in veterans and non-veterans in England: a cross-sectional survey
Authors: Greig F , McManus S , Fear N T 
Published: December 2020

Abstract

Background
Concerns have been raised that military veterans are at greater risk of dementia due to increased rates of depression, post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) found in this population. The prevalence of dementia in English veterans and whether this is different to non-veterans, however, are currently unknown.

Aims
To study the risk of dementia in the English veteran population, we aimed to calculate the prevalence of dementia in a group of veterans and compare this with a similar group, with no history of military service.

Methods
Male veterans and non-veterans aged over 64 years old were identified from the 2007 Adult Psychiatric Morbidity Survey, a national survey of community-dwelling adults in England. This survey was conducted via face-to-face interviews and incorporated questions on previous military service. Dementia was screened by using the modified Telephone Interview of Cognitive Status (TICS-M).

Results
A total of 496 male veterans and 294 non-veterans were identified. TICS-M scores indicated possible dementia in 24% of veterans and 26% non-veterans; after adjusting for age, the odds of possible dementia was significantly lower in veterans than non-veterans (adjusted OR 0.56; 95% CI 0.38–0.84, P &lt; 0.01).

Conclusions
English male veterans were less likely to have dementia than similar male non-veterans. This study did not find any evidence to support the view that dementia is more common in veterans than non-veterans.
The rebuilding macroeconomic theory project part II: multiple equilibria, toy models, and policy models in a new macroeconomic paradigm
Authors: Vines David , Wills Samuel 
Published: December 2020

AbstractThis issue of the Oxford Review of Economic Policy is the second in the Rebuilding Macroeconomic Theory project. The papers in the first issue proposed specific improvements to the New-Keynesian Dynamic Stochastic General Equilibrium (NK-DSGE) framework, in response to the events of the 2008 crisis. This issue goes further. We, as editors, now argue that a new multiple-equilibrium and diverse (MEADE) paradigm is needed for macroeconomics. It will emphasize that economies can have more than one stable outcome, and study why. It will require using both toy models, which enable a quick, first-pass, intuitive understanding of a question, and policy models (aka structural economic models) which develop a detailed empirical understanding of the economy. We argue that the seminal IS/LM, Solow–Swan, Ramsey, Real Business Cycle, Taylor, and Clarida/Galí/Gertler models have all been toys, as is the benchmark NK-DSGE model. In the past the models have adapted as the questions changed, and the NK-DSGE model must now do this since it has failed to capture both the salient aspects of the lead-up to the 2008 crisis and the slow recovery afterwards. The way forward in the MEADE paradigm will be to start with simple models, ideally two-dimensional sketches, that explain mechanisms that can cause multiple equilibria. These mechanisms should then be incorporated into larger DSGE models in a new, multiple-equilibrium synthesis. All of this will need to be informed by closer fidelity to the data, drawing on lessons obtained from detailed work on policy models.
The Long-Term and System-Level Impacts of Institutionalizing Hot Spot Policing in a Small City
Authors: Koper Christopher S , Lum Cynthia , Wu Xiaoyun , Hegarty Tim 
Published: December 2020

AbstractNumerous studies have shown that hot spot policing (HSP) is effective in reducing crime in small high-risk locations. However, questions remain about the efficacy of HSP outside large cities, its long-term sustainability and effects, and its ability to produce aggregate reductions in crime across large areas. This study highlights a small city police agency that has sustained a systematic, citywide HSP patrol strategy since 2013. A quasi-experimental assessment using nearly 7 years of follow-up data shows the programme reduced crime in targeted hot spots without displacement. Citywide, citizen calls about crime and disorder fell by 14%, with reductions ranging from 12% for disorder calls to 41% for violence calls. This study shows the value of HSP in smaller jurisdictions and supports the theory that HSP can produce large-scale, long-term reductions in crime and disorder when practiced in a manner that has sufficient targeting, dosage, tracking, management, and commitment from leadership.
Determinants of stage at diagnosis of HPV-related cancer including area deprivation and clinical factors
Authors: Chakravarthy Rohini , Stallings Sarah C , Velez Edwards Digna R , Zhao Sifang Kathy , Conway Douglas , Rao J Sunil , Aldrich Melinda C , Kobetz Erin , Wilkins Consuelo H 
Published: December 2020

Abstract

Background
Collecting social determinants of health in electronic health records is time-consuming. Meanwhile, an Area Deprivation Index (ADI) aggregates sociodemographic information from census data. The objective of this study was to ascertain whether ADI is associated with stage of human papillomavirus (HPV)-related cancer at diagnosis.

Methods
We tested for the association between the stage of HPV-related cancer presentation and ADI as well as the association between stage and the value of each census-based measure using ordered logistic regression, adjusting for age, race and sex.

Results
Among 3247 cases of HPV-related cancers presenting to an urban academic medical center, the average age at diagnosis was 57. The average stage at diagnosis was Surveillance, Epidemiology and End Results Stage 3. In the study population, 43% of patients were female and 87% were white. In this study population, there was no association between stage of HPV-related cancer presentation and either aggregate or individual census variables.

Conclusions
These results may reflect insufficient sample size, a lack of socio-demographic diversity in our population, or suggest that simplifying social determinants of health into a single geocoded index is not a reliable surrogate for assessing a patient’s risk for HPV-related cancer.
Efficient Programs to Support Businesses During and After Lockdowns*
Authors: Philippon Thomas 
Published: December 2020

Abstract
I analyze efficient government interventions to mitigate financial distress during a severe macroeconomic downturn. At the macroeconomic level, the key variable is the gap between the real wage and the shadow cost of labor. This gap is large when unemployment is high. At the micro level, laissez-faire leads to excessive liquidation of businesses but an indiscriminate bailout prevents efficient reallocations and implies a large transfer from taxpayers to existing private creditors. I show that a cost-efficient intervention can be achieved with a continuation premium, whereby the government agrees to reduce its claims by the same haircut as private creditors plus a fixed premium. (JEL D24, G33, G38, H12)
Received November 17, 2020; editorial decision November 23, 2020 by Editor Andrew Ellul.
Childhood Trauma and Psychotic Symptomatology in Ethnic Minorities With Schizophrenia
Authors: Levit Jeremy , Valderrama Jorge , Georgakopoulos Penelope ,   AA-GPC Brooklyn, Hansen Stella Kim , Salisu Margaret , Valderrama Jorge , Georgakopoulos Penelope , Fanous Ayman , Bigdeli Tim , Knowles James , Pato Carlos , Pato Michele , Pato Carlos N , Pato Michele T 
Published: December 2020

Abstract
In response to recent findings implicating trauma in the phenomenology of psychosis, this study explored interactions between adverse childhood experiences (ACEs) and positive symptoms of psychosis in an understudied patient population, comprising individuals of African and Latino ancestry. Endorsement of ACEs was compared between 90 schizophrenia cases and 240 nonpsychotic controls, matched for ethnicity, gender, and age. Relative to controls, cases reported significantly greater exposure to physical abuse, emotional abuse, sexual abuse, neglect, witnessing domestic violence, and household member incarceration. Analyses further evaluated associations between ACEs and subtypes of hallucinations, delusions, and subjective thought disorder. Among female cases, the number of hallucinatory symptoms present increased with increasing ACE score. Hallucinatory symptoms further correlated with individual ACE items. For instance, third-person voices were more common among women exposed to childhood physical and emotional abuse. Interestingly, among women, grandiose delusions were negatively related to sexual abuse, perhaps reflecting the deleterious effects of sexual trauma on the development of a positive self-concept. Among male cases, no positive relationships with hallucinations were observed, but several delusional symptoms were correlated with childhood trauma experiences. The most statistically powerful ACE associations, in both males and females, were observed with experiences of thought broadcasting. This article further advocates for the consideration of ethnicity and gender as factors influencing trauma exposures and their clinical manifestations.
Prevalence of Major Cardiovascular Disease Events Among People Diagnosed With Schizophrenia Who Have Sleep Disturbance, Sedentary Behavior, or Muscular Weakness
Authors: Berry Alexandra , Yung Alison R , Carr Matthew J , Webb Roger T , Ashcroft Darren M , Firth Joseph , Drake Richard J 
Published: December 2020

AbstractObjectiveTo estimate prevalence of major cardiovascular events among people with schizophrenia who had experience of sleep disturbance, sedentary behavior or muscular weakness, and assess evidence for raised prevalence in these individuals compared to people with schizophrenia without these characteristics.MethodsUK Biobank data on individuals diagnosed with schizophrenia (n = 1544) were used to examine the prevalence of major cardiovascular events, specifically myocardial infarction, stroke, heart failure and cardiovascular death, among participants with candidate risk factors. Generalized linear models were fitted to estimate prevalence ratios (PRs) for major cardiovascular events among participants with self-reported sleep disturbance, self-reported sedentary behavior, and muscular weakness measured using a handgrip dynamometer. These ratios were adjusted for QRISK3 score—a validated cardiovascular risk prediction algorithm for the UK population.ResultsPrevalence of major cardiovascular events was significantly higher among participants with daytime sleepiness, independent of QRISK3 score, and snoring, a proxy for sleep-disordered breathing (adjusted PR 1.26; 95% CI 1.03, 1.55, P = .03). Prevalence was also independently higher among participants with low muscular strength (adjusted PR1.36; 95% CI 1.05, 1.75, P = .02). The adjusted prevalence ratios among participants with short or prolonged sleep duration, insomnia, or sedentary behavior did not indicate independently raised prevalence among these groups.ConclusionPrevalence of major cardiovascular events among people with schizophrenia was higher in participants with muscular weakness and sleep disturbance evidenced by daytime sleepiness. Further research is required to determine how these factors can be routinely identified and addressed in the clinical management of cardiovascular risk among patients with schizophrenia.
The Value of Supporting Education Research in the Academic Environment: The Hospital for Special Surgery Academy of Rheumatology Medical Educators
Authors: Berman Jessica R. , Aizer Juliet , Tiongson Michael D. , Bass Anne R. , Parrish Edward J. , Robbins Laura , Paget Stephen A. 
Published: December 2020

Problem
Medical education academies have been instrumental in providing greater recognition of and promotion for clinician–educators. However, producing education scholarship is essential for clinician–scholar–educator career advancement. Grant funding for education research and protected time to produce scholarship are still lacking for interested physicians, in part due to institutional budget constraints and competing priorities.

Approach
The Hospital for Special Surgery Academy of Rheumatology Medical Educators was founded in 2011 to promote education scholarship through grants awarded to educators interested in research. Educators were asked to submit proposals aimed at the development of new teaching programs and curricular change. Selected applicants received up to $50,000 per year for one year. Grant money was obtained through directed fundraising from donors. Information from annual grant updates and survey responses from grant recipients in 2017 were used to assess the academy’s effectiveness.

Outcomes
Since 2012, 32 grants have been awarded, totaling $954,045 in funding. Recipients have produced national meeting abstracts, posters, oral presentations, and manuscripts and created unique curricula and electronic learning tools for medical students, residents, fellows, faculty, and patients. Four educators with demonstrated interest and research outcomes were identified during the pilot and received additional funding and support from a dedicated education research assistant.

Next Steps
The academy and the innovations grants program highlight the talents of under-supported and under-recognized teaching faculty by allowing them to distinguish themselves academically as clinician–scholar–educators. The success of these educators emphasizes the clear advantages of a formalized structure to achieve the hospital’s education goals. Next steps include providing support for a rheumatology fellow to develop an education research career rather than one in bench, clinical, or translational research.
Molecular Modification of Transient Receptor Potential Canonical 6 Channels Modulates Calcium Dyshomeostasis in a Mouse Model Relevant to Malignant Hyperthermia
Authors: Lopez Jose Rafael , Uryash Arkady , Adams Jose , Hopkins Philip M. , Allen Paul D. 
Published: December 2020

Background
Pharmacologic modulation has previously shown that transient receptor potential canonical (TRPC) channels play an important role in the pathogenesis of malignant hyperthermia. This study tested the hypothesis that genetically suppressing the function of TRPC6 can partially ameliorate muscle cation dyshomeostasis and the response to halothane in a mouse model relevant to malignant hyperthermia.

Methods
This study examined the effect of overexpressing a muscle-specific nonconducting dominant-negative TRPC6 channel in 20 RYR1-p.R163C and 20 wild-type mice and an equal number of nonexpressing controls, using calcium- and sodium-selective microelectrodes and Western blots.

Results

RYR1-p.R163C mouse muscles have chronically elevated intracellular calcium and sodium levels compared to wild-type muscles. Transgenic expression of the nonconducting TRPC6 channel reduced intracellular calcium from 331 ± 34 nM (mean ± SD) to 190 ± 27 nM (P < 0.0001) and sodium from 15 ± 1 mM to 11 ± 1 mM (P < 0.0001). Its expression lowered the increase in intracellular Ca2+ of the TRPC6-specific activator hyperforin in RYR1-p.R163C muscle fibers from 52% (348 ± 37 nM to 537 ± 70 nM) to 14% (185 ± 11 nM to 210 ± 44 nM). Western blot analysis of TRPC3 and TRPC6 expression showed the expected increase in TRPC6 caused by overexpression of its dominant-negative transgene and a compensatory increase in expression of TRPC3. Although expression of the muscle-specific dominant-negative TRPC6 was able to modulate the increase in intracellular calcium during halothane exposure and prolonged life (35 ± 5 min vs. 15 ± 3 min; P < 0.0001), a slow, steady increase in calcium began after 20 min of halothane exposure, which eventually led to death.

Conclusions
These data support previous findings that TRPC channels play an important role in causing the intracellular calcium and sodium dyshomeostasis associated with RYR1 variants that are pathogenic for malignant hyperthermia. However, they also show that modulating TRPC channels alone is not sufficient to prevent the lethal effect of exposure to volatile anesthetic malignant hyperthermia–triggering agents.

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