bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon and nutrient physiology in shrubs at the upper limits: a multispecies study
Authors: Wang Xue , Yu Fei-Hai , Jiang Yong , Li Mai-He
Published: December 2020

Aims

Carbon and nutrient physiology of trees at their upper limits have been extensively studied, but those of shrubs at their upper limits have received much less attention. The aim of this study is to examine the general patterns of nonstructural carbohydrates (NSCs), nitrogen (N) and phosphorous (P) in shrubs at the upper limits, and to assess whether such patterns are similar to those in trees at the upper limits.

Methods

Across Eurasia, we measured the concentrations of soluble sugars, starch, total NSCs, N and P in leaves, branches and fine roots (<0.5 cm in diameter) of five shrub species growing at both the upper limits and lower elevations in both summer (peak growing season) and winter (dormancy season).

Important Findings

Neither elevation nor season had significant effects on tissue N and P concentrations, except for lower P concentrations in fine roots in winter than in summer. Total NSCs and soluble sugars in branches were significantly higher in winter than in summer. There were significant interactive effects between elevation and season for total NSCs, starch, soluble sugars and the ratio of soluble sugar to starch in fine roots, showing lower soluble sugars and starch in fine roots at the upper limits than at the lower elevations in winter but not in summer. These results suggest that the carbon physiology of roots in winter may play an important role in determining the upward distribution of shrubs, like that in the alpine tree-line trees.
Rites, Rights, Rastafari! Statehood and Statecraft in Jamaica, c. 1930–1961
Authors: Osborne Myles
Published: December 2020

This article focuses on the ways Rastafari in Jamaica practiced statehood and statecraft between the 1930s and early 1960s. At times, as is well known, Rastafari rejected the authority and institutions of the colonial state in Jamaica. But archival documents also reveal the ways they came to battle against colonialism and white supremacy on their own terms. Rastas built their own versions of state institutions to recreate an alternate world beyond “Babylon.” They learned to manipulate and “work” the institutions of Babylon from law courts to the political machine in order to survive. They followed national and international news—often from Africa—and absorbed knowledge about the United Nations they could use to fight legal cases and write petitions protesting the conditions of their existence. All this suggests a novel stream of Rastafari intellectual thought and action that we must add to our understandings of the movement. Studying Rastafari in this manner—possible because of extensive research in its rich history—provides an opportunity to understand the actions of marginalized groups acting beyond the traditional nation state in the moment of decolonization.
Phenolamides in plants: an update on their function, regulation, and origin of their biosynthetic enzymes
Authors: Roumani Marwa , Besseau Sébastien , Gagneul David , Robin Christophe , Larbat Romain
Published: December 2020

Phenolamides represent a family of specialized metabolites, consisting of the association of hydroxycinnamic acid derivatives with aliphatic or aromatic amines. Since the discovery of the first phenolamide in the late 1940s, decades of phytochemical analyses have revealed a high structural diversity for this family and a wide distribution in the plant kingdom. The occurrence of structurally diverse phenolamides in almost all plant organs has led to early hypotheses on their involvement in floral initiation and fertility, as well as plant defense against biotic and abiotic stress. In the present work, we critically review the literature ascribing functional hypotheses to phenolamides and recent evidence on the control of their biosynthesis in response to biotic stress. We additionally provide a phylogenetic analysis of the numerous N-hydroxycinnamoyltransferases involved in the synthesis of phenolamides and discuss the potential role of other enzyme families in their diversification. The data presented suggest multiple evolutionary events that contributed to the extension of the taxonomic distribution and diversity of phenolamides.
Convergent Rewiring of the Virulence Regulatory Network Promotes Adaptation of Ralstonia solanacearum on Resistant Tomato
Authors: Gopalan-Nair Rekha , Jardinaud Marie-Françoise , Legrand Ludovic , Landry David , Barlet Xavier , Lopez-Roques Céline , Vandecasteele Céline , Bouchez Olivier , Genin Stéphane , Guidot Alice
Published: December 2020

The evolutionary and adaptive potential of a pathogen is a key determinant for successful host colonization and proliferation but remains poorly known for most of the pathogens. Here, we used experimental evolution combined with phenotyping, genomics, and transcriptomics to estimate the adaptive potential of the bacterial plant pathogen Ralstonia solanacearum to overcome the quantitative resistance of the tomato cultivar Hawaii 7996. After serial passaging over 300 generations, we observed pathogen adaptation to within-plant environment of the resistant cultivar but no plant resistance breakdown. Genomic sequence analysis of the adapted clones revealed few genetic alterations, but we provide evidence that all but one were gain of function mutations. Transcriptomic analyses revealed that even if different adaptive events occurred in independently evolved clones, there is convergence toward a global rewiring of the virulence regulatory network as evidenced by largely overlapping gene expression profiles. A subset of four transcription regulators, including HrpB, the activator of the type 3 secretion system regulon and EfpR, a global regulator of virulence and metabolic functions, emerged as key nodes of this regulatory network that are frequently targeted to redirect the pathogen’s physiology and improve its fitness in adverse conditions. Significant transcriptomic variations were also detected in evolved clones showing no genomic polymorphism, suggesting that epigenetic modifications regulate expression of some of the virulence network components and play a major role in adaptation as well.
Repeated Evolution of Inactive Pseudonucleases in a Fungal Branch of the Dis3/RNase II Family of Nucleases
Authors: Ballou Elizabeth R , Cook Atlanta G , Wallace Edward W J
Published: December 2020

The RNase II family of 3′–5′ exoribonucleases is present in all domains of life, and eukaryotic family members Dis3 and Dis3L2 play essential roles in RNA degradation. Ascomycete yeasts contain both Dis3 and inactive RNase II-like “pseudonucleases.” The latter function as RNA-binding proteins that affect cell growth, cytokinesis, and fungal pathogenicity. However, the evolutionary origins of these pseudonucleases are unknown: What sequence of events led to their novel function, and when did these events occur? Here, we show how RNase II pseudonuclease homologs, including Saccharomyces cerevisiae Ssd1, are descended from active Dis3L2 enzymes. During fungal evolution, active site mutations in Dis3L2 homologs have arisen at least four times, in some cases following gene duplication. In contrast, N-terminal cold-shock domains and regulatory features are conserved across diverse dikarya and mucoromycota, suggesting that the nonnuclease function requires these regions. In the basidiomycete pathogenic yeast Cryptococcus neoformans, the single Ssd1/Dis3L2 homolog is required for cytokinesis from polyploid “titan” growth stages. This phenotype of C. neoformans Ssd1/Dis3L2 deletion is consistent with those of inactive fungal pseudonucleases, yet the protein retains an active site sequence signature. We propose that a nuclease-independent function for Dis3L2 arose in an ancestral hyphae-forming fungus. This second function has been conserved across hundreds of millions of years, whereas the RNase activity was lost repeatedly in independent lineages.
PSORTdb 4.0: expanded and redesigned bacterial and archaeal protein subcellular localization database incorporating new secondary localizations
Authors: Lau Wing Yin Venus , Hoad Gemma R , Jin Vivian , Winsor Geoffrey L , Madyan Ashmeet , Gray Kristen L , Laird Matthew R , Lo Raymond , Brinkman Fiona S L
Published: December 2020

Protein subcellular localization (SCL) is important for understanding protein function, genome annotation, and aids identification of potential cell surface diagnostic markers, drug targets, or vaccine components. PSORTdb comprises ePSORTdb, a manually curated database of experimentally verified protein SCLs, and cPSORTdb, a pre-computed database of PSORTb-predicted SCLs for NCBI’s RefSeq deduced bacterial and archaeal proteomes. We now report PSORTdb 4.0 (http://db.psort.org/). It features a website refresh, in particular a more user-friendly database search. It also addresses the need to uniquely identify proteins from NCBI genomes now that GI numbers have been retired. It further expands both ePSORTdb and cPSORTdb, including additional data about novel secondary localizations, such as proteins found in bacterial outer membrane vesicles. Protein predictions in cPSORTdb have increased along with the number of available microbial genomes, from approximately 13 million when PSORTdb 3.0 was released, to over 66 million currently. Now, analyses of both complete and draft genomes are included. This expanded database will be of wide use to researchers developing SCL predictors or studying diverse microbes, including medically, agriculturally and industrially important species that have both classic or atypical cell envelope structures or vesicles.
VIPERdb v3.0: a structure-based data analytics platform for viral capsids
Authors: Montiel-Garcia Daniel , Santoyo-Rivera Nelly , Ho Phuong , Carrillo-Tripp Mauricio , III Charles L Brooks , Johnson John E , Reddy Vijay S
Published: December 2020

VIrus Particle ExploreR data base (VIPERdb) (http://viperdb.scripps.edu) is a curated repository of virus capsid structures and a database of structure-derived data along with various virus specific information. VIPERdb has been continuously improved for over 20 years and contains a number of virus structure analysis tools. The release of VIPERdb v3.0 contains new structure-based data analytics tools like Multiple Structure-based and Sequence Alignment (MSSA) to identify hot-spot residues within a selected group of structures and an anomaly detection application to analyze and curate the structure-derived data within individual virus families. At the time of this writing, there are 931 virus structures from 62 different virus families in the database. Significantly, the new release also contains a standalone database called ‘Virus World database’ (VWdb) that comprises all the characterized viruses (∼181 000) known to date, gathered from ICTVdb and NCBI, and their capsid protein sequences, organized according to their virus taxonomy with links to known structures in VIPERdb and PDB. Moreover, the new release of VIPERdb includes a service-oriented data engine to handle all the data access requests and provides an interface for futuristic data analytics using machine leaning applications.
Determinants of adenine-mutagenesis in diversity-generating retroelements
Authors: Handa Sumit , Reyna Andres , Wiryaman Timothy , Ghosh Partho
Published: December 2020

Diversity-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

Background

The 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.

Methods

This 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.

Results

Among 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).

Conclusions

Gradual 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

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

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 < 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

This 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

Numerous 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

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

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

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

Objective

To 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.

Methods

UK 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.

Results

Prevalence 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.

Conclusion

Prevalence 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.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Mutations in DNA Repair Genes and Clinical Outcomes of Patients With Metastatic Colorectal Cancer Receiving Oxaliplatin or Irinotecan-containing Regimens
Authors: Marks Eric I. , Matera Robert , Olszewski Adam J. , Yakirevich Evgeny , El-Deiry Wafik S. , Safran Howard , Carneiro Benedito A.
Published: December 2020

Objectives:

First-line regimens in the treatment of metastatic colorectal cancer (mCRC) combine a fluoropyrimidine with oxaliplatin (FOLFOX/XELOX) or irinotecan (FOLFIRI). There is limited efficacy data to guide the selection of one treatment over the other. This study investigated whether mutations affecting DNA damage response (DDR) could differentially influence the response to oxaliplatin and irinotecan-containing regimens.

Methods:

We retrospectively analyzed 49 patients with mCRC for whom treatment outcomes and results of comprehensive genomic profiling of tumors were available. Specimens with at least 1 pathogenic mutation involving BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L were classified as DDR-mutated, while those without mutations were DDR-wild-type (WT). We compared the overall survival (OS), disease control rate, and response rate (RR) between the DDR-mutated and DDR-WT groups.

Results:

DDR mutations occurred in 11 patients (22%). First-line treatment with an oxaliplatin-containing regimen was administered to 33 patients (31 FOLFOX, 2 XELOX), while 16 patients received FOLFIRI. Among DDR-mutated cases, first-line treatment with FOLFOX/XELOX correlated with a statistically significant improvement in median OS compared with FOLFIRI (3.4 vs.1.8 y; P=0.042) and numerically higher RR (50% vs. 33%; P=0.58). No significant difference in OS (2.4 vs. 2.5 y; P=0.42), RR, disease control rate was observed between the 2 regimens in patients with DDR-WT tumors.

Conclusions:

Mutations in DDR genes were present in 22% of patients with mCRC. In patients with DDR-mutated tumors, initial treatment with FOLFOX/XELOX correlated with improved OS and a numerically higher RR compared with FOLFIRI.
Preemptive Femoral-Femoral Crossover Grafting of Artery and Vein Before Pelvic Exenterative Surgery for Locally Advanced and Recurrent Pelvic Malignancy Involving the Aortoiliac Axis
Authors: Peacock Oliver , Smith Nicholas , Waters Peadar S. , Park-Yun Cheung Francis , McCormick Jacob J. , Warrier Satish K. , Wagner Timothy , Heriot Alexander G.
Published: December 2020

INTRODUCTION:

Achieving a negative resection through a pelvic exenteration for a recurrent or an advanced pelvic malignancy offers the potential for cure. Exenterative surgical units have expanded the boundaries and redefined what constitutes resectable disease through improved surgical technique. In selected cases, contiguous tumor involvement of the aortoiliac axis requires en bloc resection and subsequent vessel reconstruction. However, vascular reconstruction can be challenging in a contaminated field during an extended radical resection.

TECHNIQUE:

The aim of this Technical Note is to describe a novel method in the management of patients with recurrent or advanced pelvic malignancy involving the aortoiliac axis by performing preemptive femoral-femoral arterial and venous crossover grafts, with adjunctive arteriovenous loop fistula formation before undergoing an extended radical pelvic resection 4 weeks later.

RESULTS:

Four patients have undergone preemptive femoral-femoral arterial and venous crossover grafts at our institution (median age = 60 y (range, 47–66 y); 2 women). There were no early complications, and all of the patients subsequently underwent extended radical pelvic resections for a pelvic malignancy.

CONCLUSIONS:

Preemptive vascular reconstruction before major pelvic surgery reduces the risk of graft infection because this method avoids the wounds being contaminated by GI or genitourinary organisms. Other advantages to this technique include a reduction in the overall operating time for the pelvic exenteration, a significant reduction in the ischemia time to the lower limbs, and ensuring that the grafts are patent before embarking on major intra-abdominal surgery.
Lipoprotein(a) Reduction With Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: A Systematic Review and Meta-analysis
Authors: Farmakis Ioannis , Doundoulakis Ioannis , Pagiantza Areti , Zafeiropoulos Stefanos , Antza Christina , Karvounis Haralambos , Giannakoulas George
Published: December 2020

Lipoprotein(a) [Lp(a)] is a cardiovascular factor, for which there is no approved specific lowering treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to have lowering effects on Lp(a). Aim of this systematic review is to synthesize the current literature and quantify the effects of PCSK9 inhibitors on the serum Lp(a) levels in human subjects. Double-blind, phase 2 or 3, randomized-controlled trials comparing PCSK9 inhibitors (alirocumab or evolocumab) to placebo and/or ezetimibe and/or other lipid-lowering therapy were deemed eligible for inclusion. We searched MEDLINE (via PubMed), CENTRAL, Scopus, and Web of Science as of 17 June 2020. Quality assessment was performed using the Revised Cochrane risk-of-bias tool for randomized trials. Forty-three studies were identified (64,107 patients randomized) and 41 studies were included in the quantitative analysis. PCSK9 inhibitors reduced Lp(a) levels by −26.7% (95% CI, −29.5% to −23.9%) with a significant heterogeneity within studies. There was significant difference in Lp(a) change from baseline according to comparator (placebo: mean −27.9%; 95% CI, −31.1% to −24.6% vs. ezetimibe: mean, −22.2%; 95% CI, −27.2% to −17.2%; P = 0.04) and duration of treatment (≤12 weeks: mean, −30.9%; 95% CI, −34.7% to −27.1% vs. >12 weeks: mean, −21.9%; 95% CI, −25.2% to −18.6%; P < 0.01). Meta-regression analysis showed that only the mean percentage change from baseline low-density lipoprotein cholesterol due to the intervention is significantly associated with the effect size difference (P < 0.0001). PCSK9 inhibitors reduced low-density lipoprotein cholesterol by −54% (95% CI −57.6% to −50.6%). There is substantial efficacy of the currently approved PCSK9 inhibitors in the lowering of Lp(a) levels. Dedicated randomized controlled trials are needed to establish the benefit of this intervention.
Reducing burnout and enhancing work engagement among clinicians
Authors: Koranne Rahul , Williams Eric S. , Poplau Sara , Banks Kathryn M. , Sonneborn Mark , Britt Heather R. , Linzer Mark
Published: December 2020

Background

The Minnesota Hospital Association (MHA) recognized the impact that burnout and disengagement had on the clinician population. A clinician task force developed a conceptual framework, followed by annual surveys and a series of interventions. Features of the job demands–resources model were used as the conceptual underpinning to this analysis.

Purpose

The aim of this study was to assess the applicability of a clinician-driven conceptual model in understanding burnout and work engagement in the state of Minnesota.

Methodology

Four thousand nine hundred ninety clinicians from 94 MHA member hospitals/systems responded to a 2018 survey using a brief instrument adapted, in part, from previously validated measures.

Results

As hypothesized, job demands were strongly related to burnout, whereas resources were most related to work engagement. Variables from the MHA model explained 40% of variability in burnout and 24% of variability in work engagement. Variables related to burnout with the highest beta weights included having sufficient time for work (−0.266), values alignment with leaders (−0.176), and teamwork efficiency (−0.123), all ps < .001. Variables most associated with engagement included values alignment (0.196), feeling appreciated (0.163), and autonomy (0.093), ps < .001.

Conclusion

Findings support the basic premises of the proposed conceptual model. Remediable work–life conditions, such as having sufficient time to do the job, values alignment with leadership, teamwork efficiency, feeling appreciated, and clinician autonomy, manifested the strongest associations with burnout and work engagement.

Practice Implications

Interventions reducing job demands and strengthening resources such as values alignment, teamwork efficiency, and clinician autonomy are seen as having the greatest potential efficacy.
A state of the art review on the novel mediator asprosin in the metabolic syndrome
Authors: Luís Carla , Fernandes Rúben , Soares Raquel , von Hafe Pedro
Published: December 2020

Metabolic syndrome is a complex and heterogeneous pathology characterized by a cluster of biochemical, clinical, and metabolic factors that came together in raising the risk of cardiovascular diseases, type 2 diabetes mellitus, and all-cause mortality. Some of these features are well defined in this syndrome like: obesity, inflammation, hypertension, insulin resistance, atherosclerotic dyslipidemias, endothelial dysfunction, and inflammation. This circuit is intermediated by a complex network of hormones, cytokines, transcription factors, and adipokines, among others. Some like leptin, adiponectin, Plasminogen activator inhibitor-1, interleukin-6, Tumor necrosis factor, and their influence on the metabolic syndrome are well described in the literature and new players are described continuously. One novel player was described in 2016 by Romere et al as a fasting-induced glycogenic protein hormone named asprosin.

In order to perform a state-of-the-art, nonsystematic review of asprosin, a study of the available literature was carried out in the main database (Pubmed) and the results were studied and correlated to better understand the mechanism of action of this hormone.

Asprosin is not only associated with the metabolic syndrome features like glucose and lipid metabolism, insulin resistance, obesity and inflammation but also in other pathologies metabolic syndrome related like diabetic retinopathy, polycystic ovary syndrome and anorexia nervosa. A limited number of pathways were already unveiled although much more research is needed to better understand the therapeutical potential of asprosin in the metabolic syndrome.
Older Caregivers With HIV: An Unrecognized Gap in the Literature
Authors: Lee Yookyong , Batey David S. , Clay Olivio J. , Emlet Charles A. , Fazeli Pariya L. , Vance David E.
Published: December 2020

Although the number of older people living with HIV (PLWH) is growing, prior research has focused on older PLWH as care recipients and psychosocial factors (e.g., stigma, social support) associated with their HIV care. Literature on HIV caregiving mainly focuses on family members providing care to PLWH or children of parents with HIV. There is a gap in the literature in terms of older PLWH's roles as caregivers to their family members. Thanks to combination antiretrovirals that help PLWH live longer and have healthier lives, many older PLWH now find themselves in a position to provide care to family members. To help older PLWH age successfully, it is important to understand their role as caregivers while they juggle responsibilities with their own health care needs. This article elucidates this gap in the literature on older PLWH who are caregivers and provides direction for a research agenda and potential clinical implications.
Barriers to Cervical Cancer Screening Among Women Living With HIV in Low- and Middle-Income Countries: A Systematic Review
Authors: Guillaume Dominique , Chandler Rasheeta , Igbinoba Shanna
Published: December 2020

Women living with HIV in low-and-middle-income countries (LMICs) are at high risk of developing cervical cancer due to their immunocompromised status. Screening is an imperative prevention measure for early detection and for ultimately reducing high rates of cervical cancer; however, cervical cancer screening uptake among this group remains low. This systematic review aimed to identify barriers to cervical cancer screening among women living with HIV in LMIC. A comprehensive literature search was undertaken, and an analysis of included studies was completed to abstract major themes related to cervical cancer screening barriers for women living with HIV in LMIC. Lack of cervical cancer and cervical cancer screening knowledge among patients was found to be the most prevalent barrier to cervical cancer screening. Our findings highlight a dire need for interventions to increase knowledge and awareness of cervical cancer screening among women living with HIV in LMIC, along with addressing barriers within health care systems.
Ability to Cope by Family Caregivers of People Living With HIV in the Yi Population in Liangshan Prefecture: A Cross-sectional Study
Authors: Wang Xia , Yin Yao , Wang Huan , Chen Hong
Published: December 2020

Informal caregivers' abilities to provide care for people living with HIV plays an essential role in improving health outcomes. Little is known about caregivers in the Yi population. A cross-sectional study was conducted, and 216 participants completed the Chinese version of the Caregiver Task Inventory (CTI-C). The total mean CTI-C score was 17.46 (SD = 7.70), which showed a low level of caring ability. Regression analysis indicated that caregiving willingness and caring time were significantly positively associated with CTI-C scores. Knowledge regarding HIV was negatively associated with CTI-C scores. There is an urgent need to increase the level of HIV-related knowledge in the rural regions of Liangshan Prefecture. Education contributes to improved knowledge. Therefore, educational campaigns should be implemented to improve this situation. The local government should plan policies to improve educational levels and develop targeted knowledge-improving programs based on cultural background.