bluuebunny/crossref_metadata_2025 huggingface dataset:
Exon and protein positioning in a pre-catalytic group II intron RNP primed for splicing
Authors: Liu Nan , Dong Xiaolong , Hu Cuixia , Zeng Jianwei , Wang Jiawei , Wang Jia , Wang Hong-Wei , Belfort Marlene
Published: October 2020

Group II introns are the putative progenitors of nuclear spliceosomal introns and use the same two-step splicing pathway. In the cell, the intron RNA forms a ribonucleoprotein (RNP) complex with the intron-encoded protein (IEP), which is essential for splicing. Although structures of spliced group II intron RNAs and RNP complexes have been characterized, structural insights into the splicing process remain enigmatic due to lack of pre-catalytic structural models. Here, we report two cryo-EM structures of endogenously produced group II intron RNPs trapped in their pre-catalytic state. Comparison of the catalytically activated precursor RNP to its previously reported spliced counterpart allowed identification of key structural rearrangements accompanying splicing, including a remodeled active site and engagement of the exons. Importantly, altered RNA–protein interactions were observed upon splicing among the RNP complexes. Furthermore, analysis of the catalytically inert precursor RNP demonstrated the structural impact of the formation of the active site on RNP architecture. Taken together, our results not only fill a gap in understanding the structural basis of IEP-assisted group II intron splicing, but also provide parallels to evolutionarily related spliceosomal splicing.
The immunorecognition, subcellular compartmentalization, and physicochemical properties of nucleic acid nanoparticles can be controlled by composition modification
Authors: Johnson Morgan Brittany , Halman Justin R , Miller Daniel K , Cooper Joseph S , Khisamutdinov Emil F , Marriott Ian , Afonin Kirill A
Published: October 2020

Nucleic acid nanoparticles (NANPs) have become powerful new platforms as therapeutic and diagnostic tools due to the innate biological ability of nucleic acids to identify target molecules or silence genes involved in disease pathways. However, the clinical application of NANPs has been limited by factors such as chemical instability, inefficient intracellular delivery, and the triggering of detrimental inflammatory responses following innate immune recognition of nucleic acids. Here, we have studied the effects of altering the chemical composition of a circumscribed panel of NANPs that share the same connectivity, shape, size, charge and sequences. We show that replacing RNA strands with either DNA or chemical analogs increases the enzymatic and thermodynamic stability of NANPs. Furthermore, we have found that such composition changes affect delivery efficiency and determine subcellular localization, effects that could permit the targeted delivery of NANP-based therapeutics and diagnostics. Importantly, we have determined that altering NANP composition can dictate the degree and mechanisms by which cell immune responses are initiated. While RNA NANPs trigger both TLR7 and RIG-I mediated cytokine and interferon production, DNA NANPs stimulate minimal immune activation. Importantly, incorporation of 2′F modifications abrogates RNA NANP activation of TLR7 but permits RIG-I dependent immune responses. Furthermore, 2′F modifications of DNA NANPs significantly enhances RIG-I mediated production of both proinflammatory cytokines and interferons. Collectively this indicates that off-target effects may be reduced and/or desirable immune responses evoked based upon NANPs modifications. Together, our studies show that NANP composition provides a simple way of controlling the immunostimulatory potential, and physicochemical and delivery characteristics, of such platforms.
A Roadmap for Developing Plasma Diagnostic and Prognostic Biomarkers of Cerebral Cavernous Angioma With Symptomatic Hemorrhage (CASH)
Authors: Girard Romuald , Li Yan , Stadnik Agnieszka , Shenkar Robert , Hobson Nicholas , Romanos Sharbel , Srinath Abhinav , Moore Thomas , Lightle Rhonda , Shkoukani Abdallah , Akers Amy , Carroll Timothy , Christoforidis Gregory A , Koenig James I , Lee Cornelia , Piedad Kristina , Greenberg Steven M , Kim Helen , Flemming Kelly D , Ji Yuan , Awad Issam A
Published: October 2020

BACKGROUND

Cerebral cavernous angioma (CA) is a capillary microangiopathy predisposing more than a million Americans to premature risk of brain hemorrhage. CA with recent symptomatic hemorrhage (SH), most likely to re-bleed with serious clinical sequelae, is the primary focus of therapeutic development. Signaling aberrations in CA include proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammatory/immune processes, and anticoagulant vascular domain. Plasma levels of molecules reflecting these mechanisms and measures of vascular permeability and iron deposition on magnetic resonance imaging are biomarkers that have been correlated with CA hemorrhage.

OBJECTIVE

To optimize these biomarkers to accurately diagnose cavernous angioma with symptomatic hemorrhage (CASH), prognosticate the risk of future SH, and monitor cases after a bleed and in response to therapy.

METHODS

Additional candidate biomarkers, emerging from ongoing mechanistic and differential transcriptome studies, would further enhance the sensitivity and specificity of diagnosis and prediction of CASH. Integrative combinations of levels of plasma proteins and characteristic micro-ribonucleic acids may further strengthen biomarker associations. We will deploy advanced statistical and machine learning approaches for the integration of novel candidate biomarkers, rejecting noncorrelated candidates, and determining the best clustering and weighing of combined biomarker contributions.

EXPECTED OUTCOMES

With the expertise of leading CA researchers, this project anticipates the development of future blood tests for the diagnosis and prediction of CASH to clinically advance towards precision medicine.

DISCUSSION

The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease with a relevant context of use, with an approach applicable to other neurological diseases with similar pathobiologic features.
Damned If You Do and Damned If You Don’t: The Use of Prime Ministerial Discretion and the Royal Prerogative
Authors: Cladi Lorenzo
Published: October 2020

The royal prerogative is one of the most significant elements of the UK’s government and constitution. During the premiership of Gordon Brown and the Conservative-Liberal Democrat coalition led by David Cameron, there was momentum for a reform of the royal prerogative. During the Conservative premiership of Theresa May, the impetus for reform of the royal prerogative has seemingly diminished. This article analyses how the UK Government has made use of the royal prerogative in terms of deploying the armed forces, making and unmaking international treaties and proroguing Parliament. It asserts that while such powers have not been compromised, the ability of Prime Ministers to use them without parliamentary consent has been subject to greater contestation. This has appeared to rein in the discretion of Prime Ministers. However, this article argues that Prime Ministers’ discretion has in fact become more meaningful as their political capital is invested in decisions concerning prerogative powers.
Banking Crises Without Panics*
Authors: Baron Matthew , Verner Emil , Xiong Wei
Published: October 2020

We examine historical banking crises through the lens of bank equity declines, which cover a broad sample of episodes of banking distress with and without banking panics. To do this, we construct a new data set on bank equity returns and narrative information on banking panics for 46 countries over the period of 1870 to 2016. We find that even in the absence of panics, large bank equity declines are associated with substantial credit contractions and output gaps. Although panics are an important amplification mechanism, our results indicate that panics are not necessary for banking crises to have severe economic consequences. Furthermore, panics tend to be preceded by large bank equity declines, suggesting that panics are the result, rather than the cause, of earlier bank losses. We use bank equity returns to uncover a number of forgotten historical banking crises and create a banking crisis chronology that distinguishes between bank equity losses and panics.
Effect of air pollution on gout development: a nationwide population-based observational study
Authors: Hu W -S , Lin C -L
Published: October 2020

Objective

To investigate the effect of air pollution on gout development.

Methods

A total of 170318 participants were enrolled. These pollutants were considered: carbon monoxide (CO), fine particulate matter 2.5 (PM2.5), total hydrocarbons (THC) and methane (CH4). The yearly average concentrations were calculated from 2000 to 2011. Univariate and multivariate analyses by Cox proportional hazard regression models were adopted to estimate hazard ratios for gout in the Q2–Q4 concentrations of air pollutants compared with the Q1 concentration.

Results

In THC, relative to the Q1 concentration, the risk of gout was higher in participants exposed to the Q2–Q4 concentrations [adjusted hazard ratio (aHR), 1.10 with 95% confidence interval (CI), 1.01–1.19 in the Q2 concentration of THC; aHR, 4.20 with 95% CI, 3.93–4.49 in the Q3 concentration of THC; aHR, 5.65 with 95% CI, 5.29–6.04 in the Q4 concentration of THC]. In regard to CH4, when the Q1 concentration was defined as the reference, the risks of gout were increased for participants exposed to the Q2, Q3 and Q4 concentrations (aHR, 1.16 with 95% CI, 1.06–1.26 in the Q2 concentration of CH4; aHR, 2.37 with 95% CI, 2.20–2.55 in the Q3 concentration of CH4; aHR, 8.73 with 95% CI, 8.16–9.34 in the Q4 concentration of CH4).

Conclusions

Association between air pollution and risk of gout was noted.
Patterns of fatigue and association with disease activity and clinical manifestations in systemic lupus erythematosus
Authors: Arnaud Laurent , Mertz Philippe , Amoura Zahir , Voll Reinhard E , Schwarting Andreas , Maurier François , Blaison Gilles , Bonnotte Bernard , Poindron Vincent , Fiehn Christoph , Lorenz Hanns-Martin , Korganow Anne-Sophie , Sibilia Jean , Martin Thierry
Published: October 2020

Objective

The prevalence of fatigue is high in patients with systemic lupus erythematosus (SLE). In this study, we used latent class analysis to reveal patterns of fatigue, anxiety, depression and organ involvement in a large international cohort of SLE patients.

Methods

We used the Lupus BioBank of the upper Rhein to analyse patterns of fatigue using latent class analysis (LCA). After determining the optimal number of latent classes, patients were assigned according to model generated probabilities, and characteristics of classes were compared.

Results

A total of 502 patients were included. Significant fatigue, anxiety and depression were reported by 341 (67.9%), 159 (31.7%) and 52 (10.4%) patients, respectively. LCA revealed a first cluster (67.5% of patients) with low disease activity [median (25th–75th percentile interquartile range) Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI: 2 (0–4)], significant fatigue (55.5%, P < 0.0001), low anxiety (11.8%, P < 0.0001) and depression (0.9%, P < 0.0001). Cluster 2 (25.3%) also comprised patients with low disease activity [SELENA-SLEDAI: 2 (0–6)], but those patients had a very high prevalence of fatigue (100%, P < 0.0001), anxiety (89%, P < 0.0001) and depression (38.6%, P < 0.0001). Cluster 3 (7.2%) comprised patients with high disease activity [SELENA-SLEDAI: 12 (8–17), P < 0.0001] and high fatigue (72.2%, P < 0.0001) with low levels of anxiety (16.7%, P < 0.0001) and no depression (0%, P < 0.0001).

Conclusion

LCA revealed three patterns of fatigue with important practical implications. Based on these, it is crucial to distinguish patients with active disease (in whom remission will be achieved) from those with no or mild activity but high levels of fatigue, depression and anxiety, for whom psychological counselling should be prioritized.
Disparities in Intensive Care Unit Admission and Mortality Among Patients With Schizophrenia and COVID-19: A National Cohort Study
Authors: Fond Guillaume , Pauly Vanessa , Leone Marc , Llorca Pierre-Michel , Orleans Veronica , Loundou Anderson , Lancon Christophe , Auquier Pascal , Baumstarck Karine , Boyer Laurent
Published: October 2020

Patients with schizophrenia (SCZ) represent a vulnerable population who have been understudied in COVID-19 research. We aimed to establish whether health outcomes and care differed between patients with SCZ and patients without a diagnosis of severe mental illness. We conducted a population-based cohort study of all patients with identified COVID-19 and respiratory symptoms who were hospitalized in France between February and June 2020. Cases were patients who had a diagnosis of SCZ. Controls were patients who did not have a diagnosis of severe mental illness. The outcomes were in-hospital mortality and intensive care unit (ICU) admission. A total of 50 750 patients were included, of whom 823 were SCZ patients (1.6%). The SCZ patients had an increased in-hospital mortality (25.6% vs 21.7%; adjusted OR 1.30 [95% CI, 1.08–1.56], P = .0093) and a decreased ICU admission rate (23.7% vs 28.4%; adjusted OR, 0.75 [95% CI, 0.62–0.91], P = .0062) compared with controls. Significant interactions between SCZ and age for mortality and ICU admission were observed (P = .0006 and P < .0001). SCZ patients between 65 and 80 years had a significantly higher risk of death than controls of the same age (+7.89%). SCZ patients younger than 55 years had more ICU admissions (+13.93%) and SCZ patients between 65 and 80 years and older than 80 years had less ICU admissions than controls of the same age (−15.44% and −5.93%, respectively). Our findings report the existence of disparities in health and health care between SCZ patients and patients without a diagnosis of severe mental illness. These disparities differed according to the age and clinical profile of SCZ patients, suggesting the importance of personalized COVID-19 clinical management and health care strategies before, during, and after hospitalization for reducing health disparities in this vulnerable population.
Unfair inequality and the demand for redistribution: why not all inequality is equal
Authors: Ahrens Leo
Published: October 2020

Political economy research commonly expects a positive relationship between income inequality and the demand for redistribution, which is increasingly attributed to inequality aversion grounded in norms and values. However, people are not averse to a proportion of inequality that fairly results from differences in individual merit. Therefore, this study argues that the effect of inequality crucially depends on the extent to which income fairness is realized. It is primarily unfair inequality, rather than overall inequality, that affects individual redistribution support. The argument is substantiated with an empirical quantification of unfair inequality that measures whether individuals have unequal returns to their labor-related merits. Multilevel models using repeated cross-sections show that this quantification of unfair inequality can explain both within- and between-country variance in redistribution preferences and that it is a better predictor than overall inequality. The results suggest that public opinion cannot be inferred directly from the overall level of inequality.
Complete Genome Sequence Data of Nonpathogenic and Nonantagonistic Strain of Rhizobium vitis VAR06-30 Isolated From Grapevine Rhizosphere
Authors: Noutoshi Yoshiteru , Toyoda Atsushi , Ishii Tomoya , Saito Kirara , Watanabe Megumi , Kawaguchi Akira
Published: October 2020

Rhizobium (Agrobacterium) is one genus in the family Rhizobiaceae. Most of the species are epi- or endophytic bacteria which include tumorigenic or rhizogenic pathogens, root nodule bacteria, and commensal endosymbionts. Rhizobium vitis strain VAR06-30 is a commensal bacterium without pathogenicity which was isolated from a rootstock of grapevine in Japan. It also does not have antagonistic activity to the pathogenic strain of R. vitis. Here, we show the complete genome sequence data with annotation of R. vitis VAR06-30 which was analyzed by sequence reads obtained from both PacBio and Illumina platforms. This genome sequence would contribute to the understanding of evolutionary lineage and characteristics of Rhizobium commensal bacteria.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Quality of Postoperative Care after Major Orthopedic Surgery Is Correlated with Both Long-term Cardiovascular Outcome and Troponin Ic Elevation
Authors: Ausset Sylvain , Auroy Yves , Verret Catherine , Benhamou Dan , Vest Philippe , Cirodde Audrey , Lenoir Bernard
Published: October 2020

Background

The aim of this study performed in patients undergoing major orthopedic surgery was to assess the impact of changes in practice on both the incidence of postoperative myocardial ischemia (PMI) detected by serial measurements of troponin Ic and long-term cardiac outcome.

Methods

During a 3-yr period, troponin Ic was measured on the first 3 days after major orthopedic surgery in a multidisciplinary hospital. After 16 months of study, postoperative care was improved. Cardiac death, myocardial infarction, and cardiac failure were considered major adverse cardiac events and were recorded during the hospital stay and the first postoperative year. The incidences of PMI and major adverse cardiac events were used as result indicators for quality of care and compared before (P1) and after (P2) quality enhancement.

Results

Three hundred seventy-eight surgical procedures were included (P1, 123; P2, 255). Incidences of PMI and major adverse cardiac events were 8.9 versus 3.9% (P=0.04) and 8.1 versus 1.9% (P=0.004) for P1 and P2, respectively. Using a multivariate Cox regression analysis adjusted for baseline data, independent factors associated with the occurrence of a major adverse cardiac event were phase P1 (hazard ratio=4.5; 97.8% confidence interval [CI], 1.1-17.4) and PMI (Hazard ratio=6.4; 97.8% CI, 1.6-26.4).

Conclusions

Our postoperative care policy after major orthopedic surgery strongly correlated with both short-term cardiac outcome (i.e., PMI with troponin Ic release) and long-term cardiac outcome. Thus, in a given surgical population, variation of incidence of troponin Ic elevations could be used as a result indicator for postoperative care policy.
Late Ventilator-Induced Diaphragmatic Dysfunction After Extubation
Authors: Dridi Haikel , Jung Boris , Yehya Mohamad , Daurat Aurelien , Reiken Steven , Moreau Johan , Marks Andrew R. , Matecki Stefan , Lacampagne Alain , Jaber Samir
Published: October 2020

Objectives:

Mechanical ventilation is associated with primary diaphragmatic dysfunction, also termed ventilator-induced diaphragmatic dysfunction. Studies evaluating diaphragmatic function recovery after extubation are lacking. We evaluated early and late recoveries from ventilator-induced diaphragmatic dysfunction in a mouse model.

Design:

Experimental randomized study.

Setting:

Research laboratory.

Subjects:

C57/BL6 mice.

Interventions:

Six groups of C57/BL6 mice. Mice were ventilated for 6 hours and then euthanatized immediately (n = 18), or 1 (n = 18) or 10 days after extubation with (n = 5) and without S107 (n = 16) treatment. Mice euthanatized immediately after 6 hours of anesthesia (n = 15) or after 6 hours of anesthesia and 10 days of recovery (n = 5) served as controls.

Measurements and Main Results:

For each group, diaphragm force production, posttranslational modification of ryanodine receptor, oxidative stress, proteolysis, and cross-sectional areas were evaluated. After 6 hours of mechanical ventilation, diaphragm force production was decreased by 25–30%, restored to the control levels 1 day after extubation, and secondarily decreased by 20% 10 days after extubation compared with controls. Ryanodine receptor was protein kinase A-hyperphosphorylated, S-nitrosylated, oxidized, and depleted of its stabilizing subunit calstabin-1 6 hours after the onset of the mechanical ventilation, 1 and 10 days after extubation. Post extubation treatment with S107, a Rycal drug that stabilizes the ryanodine complex, did reverse the loss of diaphragmatic force associated with mechanical ventilation. Total protein oxidation was restored to the control levels 1 day after extubation. Markers of proteolysis including calpain 1 and calpain 2 remained activated 10 days after extubation without significant changes in cross-sectional areas.

Conclusions:

We report that mechanical ventilation is associated with a late diaphragmatic dysfunction related to a structural alteration of the ryanodine complex that is reversed with the S107 treatment.
The Use of Central Venous to Arterial Carbon Dioxide Tension Gap for Outcome Prediction in Critically Ill Patients: A Systematic Review and Meta-Analysis*
Authors: Al Duhailib Zainab , Hegazy Ahmed F. , Lalli Raj , Fiorini Kyle , Priestap Fran , Iansavichene Alla , Slessarev Marat
Published: October 2020

Objectives:

In this systematic review and meta-analysis, we assessed whether a high Co
2 gap predicts mortality in adult critically ill patients with circulatory shock.

Data Sources:

A systematic search of MEDLINE and EMBASE electronic databases from inception to October 2019.

Study Selection:

Studies from adult (age ≥ 18 yr) ICU patients with shock reporting Co
2 gap and outcomes of interest. Case reports and conference abstracts were excluded.

Data Extraction:

Data extraction and study quality assessment were performed independently in duplicate.

Data Synthesis:

We used the Newcastle-Ottawa Scale to assess methodological study quality. Effect sizes were pooled using a random-effects model. The primary outcome was mortality (28 d and hospital). Secondary outcomes were ICU length of stay, hospital length of stay, duration of mechanical ventilation, use of renal replacement therapy, use of vasopressors and inotropes, and association with cardiac index, lactate, and central venous oxygen saturation.

Conclusions:

We included 21 studies (n = 2,155 patients) from medical (n = 925), cardiovascular (n = 685), surgical (n = 483), and mixed (n = 62) ICUs. A high Co
2 gap was associated with increased mortality (odds ratio, 2.22; 95% CI, 1.30–3.82; p = 0.004) in patients with shock, but only those from medical and surgical ICUs. A high Co
2 gap was associated with higher lactate levels (mean difference 0.44 mmol/L; 95% CI, 0.20–0.68 mmol/L; p = 0.0004), lower cardiac index (mean difference, –0.76 L/min/m2; 95% CI, –1.04 to –0.49 L/min/m2; p = 0.00001), and central venous oxygen saturation (mean difference, –5.07; 95% CI, –7.78 to –2.37; p = 0.0002). A high Co
2 gap was not associated with longer ICU or hospital length of stays, requirement for renal replacement therapy, longer duration of mechanical ventilation, or higher vasopressors and inotropes use. Future studies should evaluate whether resuscitation aimed at closing the Co
2 gap improves mortality in shock.
Predicting the Future Course of Opioid Overdose Mortality: An Example From Two US States
Authors: Sumetsky Natalie , Mair Christina , Wheeler-Martin Katherine , Cerda Magdalena , Waller Lance A. , Ponicki William R. , Gruenewald Paul J.
Published: October 2020

Background:

The rapid growth of opioid abuse and the related mortality across the United States has spurred the development of predictive models for the allocation of public health resources. These models should characterize heterogeneous growth across states using a drug epidemic framework that enables assessments of epidemic onset, rates of growth, and limited capacities for epidemic growth.

Methods:

We used opioid overdose mortality data for 146 North and South Carolina counties from 2001 through 2014 to compare the retrodictive and predictive performance of a logistic growth model that parameterizes onsets, growth, and carrying capacity within a traditional Bayesian Poisson space–time model.

Results:

In fitting the models to past data, the performance of the logistic growth model was superior to the standard Bayesian Poisson space–time model (deviance information criterion: 8,088 vs. 8,256), with reduced spatial and independent errors. Predictively, the logistic model more accurately estimated fatality rates 1, 2, and 3 years in the future (root mean squared error medians were lower for 95.7% of counties from 2012 to 2014). Capacity limits were higher in counties with greater population size, percent population age 45–64, and percent white population. Epidemic onset was associated with greater same-year and past-year incidence of overdose hospitalizations.

Conclusion:

Growth in annual rates of opioid fatalities was capacity limited, heterogeneous across counties, and spatially correlated, requiring spatial epidemic models for the accurate and reliable prediction of future outcomes related to opioid abuse. Indicators of risk are identifiable and can be used to predict future mortality outcomes.
Role of Lipid-Lowering Therapy in Low-Density Lipoprotein Cholesterol Goal Attainment: Focus on Patients With Acute Coronary Syndrome
Authors: Wang Qinqin , Liang Chun
Published: October 2020

Dyslipidemia is a major risk factor for cardiovascular (CV) disease, which is the leading cause of death globally. Acute coronary syndrome (ACS) is a common cause of death, accounting for nearly half of the global burden of CV mortality. Epidemiologic studies have identified low-density lipoprotein cholesterol (LDL-C) as an independent CV risk factor, and this is now the primary target for initiating and adjusting lipid-lowering therapies in most current guidelines. Evidence from pivotal studies supports the use of high-intensity statin therapy and a lower level for optimal LDL-C in secondary prevention of atherosclerotic CV disease, especially in patients with ACS undergoing percutaneous coronary intervention. However, current research has identified a gap between the target LDL-C goal attainment and target LDL-C levels recommended by the guidelines. Statins have proven benefits in the management of CV disease and are the cornerstone of lipid-lowering management in patients with ACS. Recent randomized controlled trials have also demonstrated the benefits of cholesterol absorption inhibitors and proprotein convertase subtilisin/kexin type 9 inhibitors. This review summarizes the current evidence for LDL-lowering therapy in patients with ACS, with an emphasis on the importance of LDL-C goal attainment, rapid LDL-C lowering, and duration of LDL-C–lowering therapy.
Adolescents and long-acting reversible contraceptives: beyond the basics
Authors: Stanton Taylor , Cizek Stephanie , Tyson Nichole
Published: October 2020

Purpose of review

The current article explores some of the more complex subtopics concerning adolescents and long-acting reversible contraceptives (LARC).

Recent findings

Recent research has highlighted ways in which LARC provision can be optimized in adolescents and has identified gaps in adolescent LARC access and utilization.

Contraceptive counseling for adolescents should be patient-centered, not necessarily LARC-first, to avoid coercion. There are increasing applications for the noncontraceptive benefits of LARC for several unique patient populations and medical conditions.
Systematic evaluation of commercially available pain management apps examining behavior change techniques
Authors: Gamwell Kaitlyn L. , Kollin Sophie R. , Gibler Robert C. , Bedree Helen , Bieniak Keely H. , Jagpal Anjana , Tran Susan T. , Hommel Kevin A. , Ramsey Rachelle R.
Published: October 2020

Mobile health (mHealth) apps have the potential to enhance pain management through the use of daily diaries, medication and appointment reminders, education, and facilitating communication between patients and providers. Although many pain management apps exist, the extent to which these apps use evidence-based behavior change techniques (BCTs) remains largely unknown, making it nearly impossible for providers to recommend apps with evidence-based strategies. This study systematically evaluated commercially available pain management apps for evidence-based BCTs and app quality. Pain management apps were identified using the search terms “pain” and “pain management” in the App and Google Play stores. Reviewed apps were specific to pain management, in English, for patients, and free. A total of 28 apps were coded using the taxonomy of BCTs. App quality was assessed using the Mobile App Rating Scale. Apps included 2 to 15 BCTs (M = 7.36) and 1 to 8 (M = 4.21) pain management–specific BCTs. Prompt intention formation, instruction, behavioral-health link, consequences, feedback, and self-monitoring were the most common BCTs used in the reviewed apps. App quality from the Mobile App Rating Scale ranged from 2.27 to 4.54 (M = 3.65) out of a possible 5, with higher scores indicating better quality. PainScale followed by Migraine Buddy demonstrated the highest number of overall and pain management BCTs as well as good quality scores. Although existing apps should be assessed through randomized controlled trials and future apps should include capabilities for electronic medical record integration, current pain management apps often use evidence-based pain management BCTs.
A review of severe acute respiratory syndrome coronavirus 2 infection in the reproductive system
Authors: Huang Hsin-Hui , Wang Peng-Hui , Yang Yi-Ping , Chou Shih-Jie , Chu Po-Wei , Wu Gwo-Jang , Chang Cheng-Chang
Published: October 2020

An outbreak of pneumonia associated with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, China, in December 2019, and has been spread worldwide rapidly now. Over 5.3-million confirmed cases and 340,000 disease-associated deaths have been found till May 25, 2020. The potential pathophysiology for SARS-CoV-2 to affect the target is via the receptor, angiotensin-converting enzyme 2 (ACE2). ACE2 can be found in the respiratory, cardiovascular, gastrointestinal tract, urinary tract, and reproductive organs such as human ovaries and Leydig cells in the testis. This receptor plays a dominant role in the fertility function. Considering the crucial roles of testicular cells of the male reproductive system, increasing numbers of studies focus on the effects of SARS-CoV-2 on the testis. In this literature, we reviewed several studies to evaluate the relevance between SARS-CoV-2, ACE receptor, and female and male reproductive system and found that the risk of being attacked by SARS-CoV-2 is higher in males than in females. Since men infected with SARS-CoV-2 virus may have the risk of impaired reproductive performance, such as the orchitis and an elevated of luteinizing hormone (LH), and additionally, SARS-CoV-2 virus may be found in semen, although the latter is still debated, all suggest that we should pay much attention to sexual transmitted disease and male fertility after recovering from COVID-19.
Combination of peroxisome proliferator–activated receptor gamma and retinoid X receptor agonists induces sodium/iodide symporter expression and inhibits cell growth of human thyroid cancer cells
Authors: Chen Jui-Yu , Wang Jane-Jen , Lee Hsin-Chen , Chi Chin-Wen , Lee Chen-Hsen , Hsu Yi-Chiung
Published: October 2020

Background:

Thyroid tumors are the most frequent neoplasm of the endocrine system. The major treatment is surgical intervention followed by radioiodine therapy. The sodium/iodide symporter (NIS) has positive expression in thyroid carcinomas with good prognoses and plays a critical role in radioiodine therapy response. Low expression of NIS always leads to tumor recurrence or treatment failure. Redifferentiation therapy is more tumor specific than chemotherapy. Peroxisome proliferator–activated receptor gamma (PPARγ) agonists and retinoids are two types of redifferentiating agents. In this study, we examined whether the PPARγ agonist rosiglitazone and retinoid X receptor (RXR) agonist bexarotene could increase NIS expression and exhibit anticancer activity in human thyroid cancer cells.

Methods:

Using a TCGA data set, we analyzed the expression of NIS (SLC5A5), PPARγ, and RXR in clinical thyroid tumors and assessed their correlations with the relapse-free survival (RFS) of thyroid tumor patients. Moreover, two human thyroid cancer cell lines, differentiated thyroid papillary BCPAP cells and follicular follicular thyroid cancer-131 cells, were treated with different concentrations of the PPARγ agonist rosiglitazone alone or in combination with the RXR agonist bexarotene. Cell growth was analyzed by the MTT assay. NIS protein expression was determined by Western blotting.

Results:

From analysis of the TCGA data set, we found that thyroid tumors have lower expression of both NIS (SLC5A5) and PPARγ than nontumor controls. Higher expression levels of NIS, PPARγ, and RXR are associated with higher RFS in patients with thyroid tumors. Moreover, rosiglitazone treatment reduced cell growth and increased NIS protein expression in thyroid cancer cells under normoxic or hypoxic conditions. In addition, bexarotene potentiated the effects of rosiglitazone on cell growth and NIS protein expression.

Conclusion:

Our results suggest that the combination of PPARγ and RXR agonists has potential as a chemotherapeutic strategy for thyroid cancer.
Hypogonadism and cancer survivorship
Authors: Faw Cory A. , Brannigan Robert E.
Published: October 2020

Purpose of review

Hypogonadism is highly prevalent among not only patients with a history of prior treatment for cancer, but also among those patients with a new oncologic diagnosis who have not yet received any cancer therapy. Hypogonadism can cause a wide array of signs and symptoms including: deceased muscle mass; increased fat mass; decreased energy, mood, and overall sense of well being; diminished bone mineral density; infertility; and impaired libido and sexual function. This purpose of this manuscript is to review the mechanisms by which cancer and oncologic treatment regimens can adversely affect the hypothalamic pituitary gonadal axis, resulting in hypogonadism. Risks and benefits associated with the treatment of testosterone deficiency are also discussed, which are important considerations for clinicians caring for affected patients.

Recent findings

Hypogonadism has a high prevalence in the setting of cancer and is an important survivorship issue. Recent randomized controlled trials confirm testosterone's therapeutic benefits in terms of sexual function, mood body composition, and bone health, but the specific benefits in terms of quality of life are less clear.

More prospective studies are needed to further delineate the risks, benefits, and overall outcomes of testosterone replacement therapy in patients with cancer and cancer survivors.
Development and Testing of Compatible Diagnosis Code Lists for the Functional Comorbidity Index: International Classification of Diseases, Ninth Revision, Clinical Modification and International Classification of Diseases, 10th Revision, Clinical Modification
Authors: Sears Jeanne M. , Rundell Sean D.
Published: October 2020

Background:

The Functional Comorbidity Index (FCI) was developed for community-based adult populations, with function as the outcome. The original FCI was a survey tool, but several International Classification of Diseases (ICD) code lists—for calculating the FCI using administrative data—have been published. However, compatible International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-CM versions have not been available.

Objective:

We developed ICD-9-CM and ICD-10-CM diagnosis code lists to optimize FCI concordance across ICD lexicons.

Research Design:

We assessed concordance and frequency distributions across ICD lexicons for the FCI and individual comorbidities. We used length of stay and discharge disposition to assess continuity of FCI criterion validity across lexicons.

Subjects:

State Inpatient Databases from Arizona, Colorado, Michigan, New Jersey, New York, Utah, and Washington State (calendar year 2015) were obtained from the Healthcare Cost and Utilization Project. State Inpatient Databases contained ICD-9-CM diagnoses for the first 3 calendar quarters of 2015 and ICD-10-CM diagnoses for the fourth quarter of 2015. Inpatients under 18 years old were excluded.

Measures:

Length of stay and discharge disposition outcomes were assessed in separate regression models. Covariates included age, sex, state, ICD lexicon, and FCI/lexicon interaction.

Results:

The FCI demonstrated stability across lexicons, despite small discrepancies in prevalence for individual comorbidities. Under ICD-9-CM, each additional comorbidity was associated with an 8.9% increase in mean length of stay and an 18.5% decrease in the odds of a routine discharge, compared with an 8.4% increase and 17.4% decrease, respectively, under ICD-10-CM.

Conclusion:

This study provides compatible ICD-9-CM and ICD-10-CM diagnosis code lists for the FCI.
Facility Variation in Troponin Ordering Within the Veterans Health Administration
Authors: Chui Philip W. , Esserman Denise , Bastian Lori A. , Curtis Jeptha P. , Gandhi Parul U. , Rosman Lindsey , Desai Nihar , Hauser Ronald G.
Published: October 2020

Background:

Current United States guidelines recommend troponin as the preferred biomarker in assessing for acute coronary syndrome, but recommendations are limited about which patients to test. Variations in troponin ordering may influence downstream health care utilization.

Methods:

We performed a cross-sectional analysis of 3,308,131 emergency department (ED) visits in all 121 acute care facilities within the Veterans Health Administration from 2015 to 2017. We quantified the degree to which case mix and facility characteristics accounted for variations in facility rates in troponin ordering. We then assessed the association between facility quartiles of risk-adjusted troponin ordering and downstream resource utilization [inpatient admissions, noninvasive testing (stress tests, echocardiograms), and invasive procedures (coronary angiograms, percutaneous coronary interventions, and coronary artery bypass grafting surgeries)].

Results:

The proportion of ED visits with troponin orders ranged from 2.2% to 64.5%, with a median of 37.1%. Case mix accounted for 9.5% of the variation in troponin orders; case mix and differences in facility characteristics accounted for 34.6%. Facilities in the highest quartile of troponin ordering, as compared with those in the lowest quartile, had significantly higher rates of inpatient admissions, stress tests, echocardiograms, coronary angiograms, and percutaneous coronary intervention.

Conclusions:

Significant variation in troponin utilization exists across Veterans Health Administration facilities and that variation is not well explained by case mix alone. Facilities with higher rates of troponin ordering were associated with more downstream resource utilization.
Pediatric Feeding Disorder in Children With Short Bowel Syndrome
Authors: Christian Vikram J. , Van Hoorn Megan , Walia Cassandra L.S. , Silverman Alan , Goday Praveen S.
Published: October 2020

Objective:

We aimed to characterize the prevalence of pediatric feeding disorder (PFD) in short bowel syndrome (SBS) and study factors contributing to the persistence of PFD.

Methods:

Single‐center retrospective study of patients diagnosed with SBS at age 6 months or younger. Data were collected in 3‐month intervals through age 2 years, and every 6 months through age 4 years. Demographic information, anthropometric data, and details regarding nutrition support were recorded and analyzed.

Results:

We reviewed 28 patients. Of the 21 patients who were weaned off parenteral nutrition, 57.1%, 81.0%, 90.5%, and 100.0% achieved this by 12, 24, 36, and 48 months of age, respectively. Of the 13 patients who were weaned off enteral nutrition, 30.8%, 69.2%, 76.9%, and 100.0% achieved this by 12, 24, 36, and 48 months, respectively.

Discussion:

The prevalence of PFD was 100.0%, 76.5%, 68.8%, and 70.0% at 1, 2, 3, and 4 years of age, respectively. All patients who exhibited resolution of PFD had an underlying etiology of necrotizing enterocolitis. Median small bowel percentage remaining was greater in patients who exhibited resolution of PFD compared to those who did not. Except for the group of patients seen at 4 years of age, a larger percentage of patients with vomiting/history of requirement of postpyloric feeds were seen among patients with PFD compared to those without PFD.

Conclusion:

PFD is prevalent in children with SBS. Although prevalence decreases over time, children with PFD will continue to require more medical attention than children that do not.
Genomic Study of Chinese Quadruple-negative GISTs Using Next-generation Sequencing Technology
Authors: Wang Si , Sun Rui-Ze , Han Qiang , Wang Si-Yao , Wang En-Hua , Liu Yang
Published: October 2020

Purpose:

Approximately 10% of gastrointestinal stromal tumors (GISTs) are devoid of KIT, PDGFRA (platelet-derived growth factor-alpha), BRAF, and SDH alterations. The aim of this study was to characterize molecular drivers in Chinese patients with quadruple-negative GISTs.

Patients and Methods:

In 1022 Chinese patients with GIST, mutations of KIT and PDGFRA were analyzed by direct sequencing. Of these mutations, 142 KIT/PDGFRA wild-type (WT) GISTs were detected, and succinate dehydrogenase (SDH) deficiency was determined using immunohistochemistry analysis of succinate dehydrogenase B. In 78 KIT
WT/PDGFRA
WT/SDH
WT cases, we performed targeted 425 cancer-related gene analysis using next-generation sequencing. The correlation between molecular findings and clinicopathologic features was also analyzed.

Results:

We defined 72 quadruple-negative GISTs from enrollments. They featured nongastric localization with histologic characteristics of spindle cells and male predilection. An overall 27.78% (20/72) of quadruple-negative tumors carried TP53, and 25.00% (18/72) carried RB1 mutations, which were frequently associated with high mitotic index and large size. TP53 analyses demonstrated coexistence with mutational activation of other oncogenes in 12 of 20 cases. A total of 18 RB1-mutated cases were independent of TP53. Further, no tumors carried NF1 and BRAF mutations.

Conclusions:

We report the genomic analysis of Chinese quadruple-negative patients. These databases may help advance our understanding of quadruple-negative GISTs’ progression. Next-generation sequencing from GISTs is feasible to provide relevant data for guiding individualized therapy.
Burnout and Resiliency Trends in Pediatric Emergency Medicine Fellows
Authors: Zargham Shiva , Rominger Annie
Published: October 2020

Objective

Burnout is a problem among physicians. Debriefing may be a tool to decrease burnout and increase resiliency in pediatric emergency medicine (PEM) providers. The objective of this study was to determine rates of burnout and resiliency in PEM fellows and their experience with debriefing.

Methods

A validated survey was administered to PEM fellows during their first and then third years of fellowship. The survey included the abbreviated Maslach Burnout Index (MBI), the Brief Resilience Scale (BRS), and debriefing experience. The percent of respondents with moderate to high burnout was determined by their scores in each of 3 MBI categories. Their resilience was determined by the BRS score. The effect of debriefing on resiliency scores was analyzed.

Results

There were 47 first-year respondents (of 148 first-year PEM fellows) and 34 third-year respondents (of 118 third-year PEM fellows). There were burnout scores in at least 1 MBI category in 80.9% of first years and 65% of third years. In first years, 42.6% showed burnout in personal accomplishment, 38.3% in depersonalization, and 55.3% in emotional exhaustion. By third year, they were 35.3%, 29.4%, and 52.9%, respectively. About 59% of first and third years had low resiliency scores. Fifty-five percent of first year respondents felt comfortable with debriefing compared with 67.6% of third years. The fellows' comfort and experience with debriefing did not significantly affect their BRS score.

Conclusions

This study shows that many first-year PEM fellows already have signs of burnout and low resiliency. However, by third year, there was improvement in burnout scores. Additional tools provided in fellowship may help prevent burnout in PEM fellows.
Rehabilitation of a Post–Intensive Care Unit Patient After Severe COVID-19 Pneumonia
Authors: Ramalingam Mothi Babu , Huang Youyi , Lim Peter A. C.
Published: October 2020

The recent novel severe acute respiratory syndrome coronavirus 2 infection resulted in a coronavirus disease 2019 pandemic that significantly strained healthcare systems globally. The early wave of patients in Singapore with severe pneumonia requiring intensive care units are gradually being referred for post–critical illness management with our inpatient medical rehabilitation unit. There is growing information regarding the actual rehabilitation process for patients severely affected by coronavirus disease 2019. This case report shares experiences and challenges faced during rehabilitation of severe coronavirus disease 2019 pneumonia and post–intensive care syndrome. It also describes the post–discharge rehabilitation program in a setting of strict nationwide safe distancing and stay-home policies.
Unilateral Hypoglossal Nerve Palsy as a COVID-19 Sequel
Authors: Costa Martins Daniela , Branco Ribeiro Sofia , Jesus Pereira Isabel , Mestre Susana , Rios Jonathan
Published: October 2020

Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 is spreading around the world, and the outbreak continues to escalate. Recently, it has been noticed that besides the typical respiratory complications, some severely affected coronavirus disease 2019 patients also experience neurological manifestations. Here, we describe the case of a newly diagnosed unilateral hypoglossal nerve palsy in a severe coronavirus disease 2019 patient. The intubation procedure was uneventful, and magnetic resonance imaging excluded the most reported causes of isolated hypoglossal nerve injury. This case reports a rare condition. Although a reasonable doubt remains, it cannot be excluded that it may be a neurological manifestation of severe acute respiratory syndrome coronavirus 2, the authors believe it to be the cause of the palsy. The main importance of this article is to alert clinicians for neurological sequels that may require a targeted rehabilitation program.