bluuebunny/crossref_metadata_2025 huggingface dataset:
Transjugular intrahepatic portosystemic shunt in refractory ascites: clinical impact of left ventricular diastolic dysfunction
Authors: Debernardi Venon Wilma , Lo Pumo Sara , Imperatrice Barbara , Giorgi Mauro , Righi Dorico , Fonio Paolo , Saracco Giorgio M. , Marzano Alfredo
Published: April 2021

Background and aims

Left ventricular diastolic dysfunction (LVDD) in cirrhotics are associated with circulatory dysfunction, hepatorenal syndrome (HRS) and heart failure in stressful conditions. Transjugular intrahepatic portosystemic shunt (TIPS) exacerbates the hyperdynamic circulation and challenges cardiac function. We evaluated the incidence and the impact of LVDD in cirrhotic candidates to TIPS for refractory ascites.

Methods

Among 135 patients who underwent TIPS for refractory ascites, 63 cases (child B/C 53/10, Na-model for end-stage liver disease 16.5 ± 0.9) who had 2D-transthoracic-echocardiography with tissue-Doppler-imaging pre-TIPS were retrospectively analysed (group A); in 23 cases cardiac and hormonal assessment before and after TIPS was available. 41 cirrhotics without refractory ascites treated by banding ligation for variceal re-bleeding were used as controls (group B).

Results

The prevalence of LVDD was higher in group A (59%; 22% with grade ≥2) as compared to group B (35%; 7% with grade ≥2) (P < 0.01 and P < 0.03). A lack of clinical response to TIPS occurred in 10 patients, all with LVDD (P < 0.03 vs. no LVDD) and in patients with grade ≥2 LVDD mostly (P < 0.02 vs. grade 1). Central venous pressure >20 mmHg after TIPS and left ventricular end-diastolic volume at basal were predictors of no response to TIPS (P = 0.01 and P = 0.004, respectively), which was an independent predictor of death. Elevated levels of NT-proBNP 3 days after TIPS were associated with advanced cardiac dysfunction (P = 0.005).

Conclusion

NT-proBNP and careful LVDD investigation are useful to better select patients and to predict clinical response and mortality after TIPS.
Small intestinal bacterial overgrowth and orocecal transit time in patients of nonalcoholic fatty liver disease
Authors: Shi Haitao , Mao Lijuan , Wang Lianli , Quan Xiaojing , Xu Xiaoyu , Cheng Yan , Zhu Shanshan , Dai Fei
Published: April 2021

Objective

The aim of the present study is to explore the frequency of small intestinal bacterial overgrowth (SIBO) and orocecal transit time (OCTT) in patients with nonalcoholic fatty liver disease (NAFLD).

Patients and methods

103 patients with NAFLD and 49 healthy controls were enrolled. Clinical indicators such as BMI, liver function, blood lipids, homeostasis model assessment-insulin resistance (HOMA-IR), serum endotoxin of NAFLD patients were collected and examined. FibroTouch was used to detect the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). SIBO and OCTT were measured by the lactulose hydrogen breath test.

Results

The incidence of SIBO in NAFLD patients (58.3%) was significantly higher than that in healthy controls (26.5%). The level of serum endotoxin in NAFLD patients was higher than that in healthy controls. The levels of CAP, LSM, serum endotoxin, alanine transaminase, asperate aminotransferase and HOMA-IR in SBIO-positive NAFLD patients were higher than those in SIBO-negative patients. There was no significant difference in glutamyl transpeptidase triglyceride, low density lipoprotein and BMI between the two groups. OCTT in NAFLD patients was longer than that in healthy controls. It was also observed that OCTT in SIBO-positive NAFLD patients was significantly delayed compared with SIBO-negative NAFLD patients.

Conclusions

Patients with NAFLD exhibit the increased incidence rate of SIBO and prolonged OCTT; SIBO in NAFLD patients maybe a contributing factor to the elevated transaminase, hepatic steatosis, progression of liver fibrosis and prolonged OCTT.
Assessment of different laboratory tests for the diagnosis of novel coronavirus infections
Authors: Ghojoghi Rozita , Zamani Bahareh , Behbahani Abbas Behzad
Published: April 2021

Rapid diagnosis of coronavirus disease 2019 (COVID-19)-infected patients is urgent in making decisions on public health measures. There are different types of diagnostic tests, such as quantitative PCR assay, antibody, and antigen-based and CRISPR-based tests, which detect genetic materials, viral proteins, or human antibodies in clinical samples. However, the proper test should be highly sensitive, quick, and affordable to address this life-threatening situation. This review article highlights the advantages and disadvantages of each test and compares its different features, such as sensitivity, specificity, and limit of detection to reach a reliable conclusion. Moreover, the FDA- authorized kits and studies’ approaches toward these have been compared to provide a better perspective to the researchers.
Utilizing electronic health record data to understand comorbidity burden among people living with HIV: a machine learning approach
Authors: Yang Xueying , Zhang Jiajia , Chen Shujie , Weissman Sharon , Olatosi Bankole , Li Xiaoming
Published: April 2021

Objectives:

An understanding of the predictors of comorbidity among people living with HIV (PLWH) is critical for effective HIV care management. In this study, we identified predictors of comorbidity burden among PLWH based on machine learning models with electronic health record (EHR) data.

Methods:

The study population are individuals with a HIV diagnosis between January 2005 and December 2016 in South Carolina (SC). The change of comorbidity burden, represented by the Charlson Comorbidity Index (CCI) score, was measured by the score difference between pre- and post-HIV diagnosis, and dichotomized into a binary outcome variable. Thirty-five risk predictors from multiple domains were used to predict the increase in comorbidity burden based on the logistic least absolute shrinkage and selection operator (Lasso) regression analysis using 80% data for model development and 20% data for validation.

Results:

Of 8253 PLWH, the mean value of the CCI score difference was 0.8 ± 1.9 (range from 0 to 21) with 2328 (28.2%) patients showing an increase in CCI score after HIV diagnosis. Top predictors for an increase in CCI score using the LASSO model included older age at HIV diagnosis, positive family history of chronic conditions, tobacco use, longer duration with retention in care, having PEBA insurance, having low recent CD4+ cell count and duration of viral suppression.

Conclusion:

The application of machine learning methods to EHR data could identify important predictors of increased comorbidity burden among PLWH with high accuracy. Results may enhance the understanding of comorbidities and provide the evidence based data for integrated HIV and comorbidity care management of PLWH.
Building a social media-based HIV risk behavior index to inform the prediction of HIV new diagnosis: a feasibility study
Authors: Li Zhenlong , Qiao Shan , Jiang Yuqin , Li Xiaoming
Published: April 2021

Objective:

Analysis of geolocation-based social media Big Data provides unprecedented opportunities for a broad range of domains including health as health is intrinsically linked to the geographic characteristics of places. HIV infection is largely driven by HIV risk behaviors, such as unsafe sexual behavior and drug abuse/addiction. This study explores the feasibility of building a Social media-based HIV Risk Behavior (SRB) index at the United States county level for informing HIV surveillance and prevention, considering social determinants of health and geographic locations.

Methods:

The SRB index, defined as the proportion of risk behavior related Twitter users among all Twitter users, was calculated at the county level for each year. To evaluate the performance of the new SRB index, the relationships between the county-level SRB and rate of new HIV diagnoses from AIDSVu were analyzed using multivariate regression while simultaneously considering five socioeconomic status (SES) factors (percentage uninsured, median household income, Gini coefficient, percentage living in poverty, percentage high school graduates) in the model. Moran's I and geographically weighted regression analyses (GWR) were leveraged to examine spatial autocorrelations and reveal the potential spatial heterogeneity (geographical variability) of the associations.

Results:

County-level multivariate regression results revealed that SRB has the strongest association with new HIV diagnosis rate (r > 0.36; P < 0.0001) in both years compared with the five SES factors. Hierarchical regression analysis suggested that the SRB index explains significant additional variance in addition to the five SES factors. The results from GWR analysis not only greatly improved the model explanation power (bringing the adjusted r-square from 0.25 to 0.47 in 2016 and 0.26 to 0.55 in 2017) but also revealed SRB index is the most spatially consistent measurement compared with the five SES factors in terms of impact direction (negative or positive correlation).

Conclusion:

It is feasible to build a social media-based HIV risk behavior index (SRB) as a new indicator for HIV surveillance at county level. The SRB index improves the regression model explanation power of new HIV diagnosis by providing additional information beyond the traditional social determinant measures, such as SES indicators. SRB index will allow researchers to utilize data captured within existing social media platforms to better understand the geospatial patterns of HIV risk behavior and to inform population-based HIV surveillance and other efforts of HIV prevention and control.
County-level predictors of retention in care status among people living with HIV in South Carolina from 2010 to 2016: a data-driven approach
Authors: Zeng Chengbo , Zhang Jiajia , Sun Xiaowen , Li Zhenlong , Weissman Sharon , Olatosi Bankole , Li Xiaoming
Published: April 2021

Objective:

The aim of this study was to examine the geospatial variation of retention in care (RIC) across the counties in South Carolina (SC) from 2010 to 2016 and identify the relevant county-level predictors.

Design:

Aggregated data on county-level RIC among HIV patients from 2010 to 2016 were retrieved from an electronic HIV/AIDS reporting system in SC Department of Health and Environmental Control. Sociological framework of health was used to select potential county-level predictors from multiple public datasets.

Methods:

Geospatial mapping was used to display the spatial heterogeneity of county-level RIC rate in SC. Generalized linear mixed effect regression with least absolute shrinkage and selection operator (LASSO) was employed to identify county-level predictors related to the change of RIC status over time. Confusion matrix and area under the curve statistics were used to evaluate model performance.

Results:

More than half of the counties had their RIC rates lower than the national average. The change of county-level RIC rate from 2010 to 2016 was not significant, and spatial heterogeneity in RIC rate was identified. A total of 22 of the 31 county-level predictors were selected by LASSO for predicting county-level RIC status. Counties with lower collective efficacy, larger proportions of men and/or persons with high education were more likely to have their RIC rates lower than the national average. In contrast, numbers of accessible mental health centres were positively related to county-level RIC status.

Conclusion:

Spatial variation in RIC could be identified, and county-level factors associated with accessible healthcare facilities and social capital significantly contributed to these variations. Structural and individual interventions targeting these factors are needed to improve the county-level RIC and reduce the spatial variation in HIV care.
Adolescent HIV-related behavioural prediction using machine learning: a foundation for precision HIV prevention
Authors: Wang Bo , Liu Feifan , Deveaux Lynette , Ash Arlene , Gosh Samiran , Li Xiaoming , Rundensteiner Elke , Cottrell Lesley , Adderley Richard , Stanton Bonita
Published: April 2021

Background:

Precision prevention is increasingly important in HIV prevention research to move beyond universal interventions to those tailored for high-risk individuals. The current study was designed to develop machine learning algorithms for predicting adolescent HIV risk behaviours.

Methods:

Comprehensive longitudinal data on adolescent risk behaviours, perceptions, peer and family influence, and neighbourhood risk factors were collected from 2564 grade-10 students at baseline followed for 24 months over 2008–2012. Machine learning techniques [support vector machine (SVM) and random forests] were applied to innovatively leverage longitudinal data for robust HIV risk behaviour prediction. In this study, we focused on two adolescent risk behaviours: had ever had sex and had multiple sex partners. Twenty percent of the data were withheld for model testing.

Results:

The SVM model with cost-sensitive learning achieved the highest sensitivity, at 79.1%, specificity of 75.4% with AUC of 0.86 in predicting multiple sex partners on the training data (10-fold cross-validation), and sensitivity of 79.7%, specificity of 76.5% with AUC of 0.86 on the testing data. The random forest model obtained the best performance in predicting had ever had sex, yielding the sensitivity of 78.5%, specificity of 73.1% with AUC of 0.84 on the training data and sensitivity of 82.7%, specificity of 75.3% with AUC of 0.87 on the testing data.

Conclusion:

Machine learning methods can be used to build effective prediction model(s) to identify adolescents who are likely to engage in HIV risk behaviours. This study builds a foundation for targeted intervention strategies and informs precision prevention efforts in school-setting.
Nutritional Assessment and Associated Factors in Children with Congenital Heart Disease - Ethiopia
Authors: Tesfaye Tigist , Tsega Temesgen , Dessie Azene , Teshome Tesfalem
Published: April 2021

Worldwide, congenital heart disease is the principal heart diseases in children and constitutes one of the major causes of infant mortality, particularly in developing countries. Infants and children with congenital heart disease exhibit a range of delays in weight gain and growth. In some instances, the delay can be relatively mild, whereas in other cases, cause the failure to thrive.

OBJECTIVES

To determine the nutritional status and associated factors of pediatric patients with congenital heart disease.

MATERIAL AND METHODS

A cross sectional analytical study was done over a period of 6months (Feb to Jul 2020). A total of 228 subjects with congenital heart disease that come to the cardiac center during the study period where included until the calculated sample size was attained. Data was collected from patient card and care givers of the children included in the study after obtaining their informed consent using data inquiry sheet. Data was then analyzed using Statistical Package for Social Sciences (SPSS) for windows version 25.0. Data is presented using tables and text form. Odds Ratio with 95% Confidence Interval (CI) was used to determine the effect of the independent variables on the outcome variable and P-value less than 0.05 was considered statistically significant.

RESULTS

A total of 228 children from age 3month to 17yrs with mean age of 4.7 years (SD=3.8 years) were included in the study. Most of the subjects had acyanotic heart disease accounting for 87.7%. The overall prevalence of wasting, underweight and stunting were 41.3%, 49.1% and 43% respectively. Among this children with congenital heart disease those with PAH were found more likely have wasting compared to those without PAH with an odds of 1.9 (95% CI: 1.0-3.4) and also greater chance of being stunted with an odds of 1.9 (95% CI: 1.0-3.4). children above 5years of age were 2.3 times more likely to be underweight.

CONCLUSION

Malnutrition is a major problem of patients with CHD. Pulmonary hypertension and older age are associated with increased risk of undernutrition.
Assessing the Risk of Cascading COVID-19 Outbreaks from Prison-to-Prison Transfers
Authors: Parsons Todd L. , Worden Lee
Published: April 2021

COVID-19 transmission has been widespread across the California prison system, and at least two of these outbreaks were caused by transfer of infected individuals between prisons. Risks of individual prison outbreaks due to introduction of the virus and of widespread transmission within prisons due to poor conditions have been documented. We examine the additional risk potentially posed by transfer between prisons that can lead to large-scale spread of outbreaks across the prison system if the rate of transfer is sufficiently high.

We estimated the threshold number of individuals transferred per prison per month to generate supercritical transmission between prisons, a condition that could lead to large-scale spread across the prison system. We obtained numerical estimates from a range of representative quantitative assumptions, and derived the percentage of transfers that must be performed with effective quarantine measures to prevent supercritical transmission given known rates of transfers occurring between California prisons.

Our mean estimate of the critical threshold rate of transfers was 14.38 individuals transferred per prison per month in the absence of quarantine measures. Available data documents transfers occurring at a rate of 60 transfers per prison per month. At that rate, estimates of the threshold rate of adherence to quarantine precautions had mean 76.03%. While the impact of vaccination and possible decarceration measures is unclear, we include estimates of the above quantities given reductions in the probability and extent of outbreaks.

We conclude that the risk of supercritical transmission between California prisons has been substantial, requiring quarantine protocols to be followed rigorously to manage this risk. The rate of outbreaks occurring in California prisons suggests that supercritical transmission may have occurred. We stress that the thresholds we estimate here do not define a safe level of transfers, even if supercritical transmission between prisons is avoided, since even low rates of transfer can cause very large outbreaks. We note that risks may persist after vaccination, due for example to variant strains, and in prison systems where widespread vaccination has not occurred. Decarceration remains urgently needed as a public health measure.
A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2
Authors: Fulford Thomas S. , Van Huy , Gherardin Nicholas A. , Zheng Shuning , Ciula Marcin , Drummer Heidi E. , Redmond Samuel , Tan Hyon-Xhi , Center Rob J. , Li Fan , Grimley Samantha L. , Wines Bruce D. , Nguyen Thi H.O. , Mordant Francesca L. , Rowntree Louise C. , Cheng Allen C. , Doolan Denise L. , Bond Katherine , Hogarth P. Mark , McQuilten Zoe , Subbarao Kanta , Kedzierska Katherine , Juno Jennifer A. , Wheatley Adam K. , Kent Stephen J. , Williamson Deborah A. , Purcell Damian F.J. , Anderson David A. , Godfrey Dale I.
Published: April 2021

As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus; whether through infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure SARS-CoV-2 immunity, ideally with rapid turnaround and without the need for laboratory-based testing. Current rapid point-of-care (POC) tests measure antibodies (Ab) against the SARS-CoV-2 virus, however, these tests provide no information on whether the antibodies can neutralise virus infectivity and are potentially protective, especially against newly emerging variants of the virus. Neutralising Antibodies (NAb) are emerging as a strong correlate of protection, but most current NAb assays require many hours or days, samples of venous blood, and access to laboratory facilities, which is especially problematic in resource-limited settings. We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibodies from whole blood, with a result that can be determined by eye (semi-quantitative) or on a small instrument (quantitative), and results show high correlation with microneutralisation assays. This assay also provides a measure of total anti-RBD antibody, thereby providing evidence of exposure to SARS-CoV-2 or immunisation, regardless of whether NAb are present in the sample. By testing samples from immunised macaques, we demonstrate that this test is equally applicable for use with animal samples, and we show that this assay is readily adaptable to test for immunity to newly emerging SARS-CoV-2 variants. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (R2 =0.75, p<0.0001), and that fingerprick whole blood samples are sufficient for this test. Accordingly, the COVID-19 NAb-test™ device described here can provide a rapid readout of immunity to SARS-CoV-2 at the point of care.
ClustENMD: Efficient sampling of biomolecular conformational space at atomic resolution
Authors: Kaynak Burak T. , Zhang She , Bahar Ivet , Doruker Pemra
Published: April 2021

Efficient sampling of conformational space is essential for elucidating functional/allosteric mechanisms of proteins and generating ensembles of conformers for docking applications. However, unbiased sampling is still a challenge especially for highly flexible and/or large systems. To address this challenge, we describe the new implementation of our computationally efficient algorithm ClustENMD that is integrated with ProDy and OpenMM softwares. This hybrid method performs iterative cycles of conformer generation using elastic network model (ENM) for deformations along global modes, followed by clustering and short molecular dynamics (MD) simulations. ProDy framework enables full automation and analysis of generated conformers and visualization of their distributions in the essential subspace.

Availability and implementation

ClustENMD is open-source and freely available under MIT License from https://github.com/prody/ProDy.

Contact

burak.kaynak@pitt.edu or doruker@pitt.edu

Supplementary information

Supplementary materials comprise method details, figures, table and tutorial.
Sleep modulates alcohol toxicity inDrosophila
Authors: Noakes Eric J. , De Nobrega Aliza K. , Mellers Alana P. , Lyons Lisa C.
Published: April 2021

Study Objectives

Alcohol abuse is a significant public health problem, particularly in populations in which sleep deprivation is common as such as shift workers and aged individuals. Although research demonstrates the effect of alcohol on sleep, little is known about the role of sleep in alcohol sensitivity and toxicity. We investigated sleep as a factor modulating alcohol toxicity usingDrosophila melanogaster, a model system ideal for studies of sleep, alcohol and aging.

Methods

Following 24 hours of sleep deprivation using mechanical stimulation,Drosophilawere exposed to binge-like alcohol exposures. Behavioral sensitivity, tolerance, and mortality were assessed. The effects of chronic sleep deprivation on alcohol toxicity were investigated using a short sleep mutantinsomniac. Pharmacological induction of sleep for prior to alcohol exposure was accomplished using a GABAA-receptor agonist, 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) to determine if increased sleep mitigated the effects of alcohol toxicity on middle-aged flies and flies with environmentally disrupted circadian clocks mimicking groups more vulnerable to the effects of alcohol.

Results

Acute sleep deprivation increased alcohol-induced mortality following alcohol exposure. However, sleep deprivation had no effect on alcohol absorbance or clearance. Sleep deprivation also abolished functional tolerance measured 24 hours after the initial alcohol exposure, although tolerance at 4 h was observed. Pharmacologically increasing sleep prior to alcohol exposure decreased alcohol-induced mortality.

Conclusions

Sleep quantity prior to alcohol exposure affects alcohol toxicity with decreased sleep increasing alcohol toxicity and dampened 24-hour alcohol tolerance. In contrast, increased sleep mitigated alcohol-induced mortality even in vulnerable groups such as aging flies and those with circadian dysfunction.

Statement of significance

With the growing incidence of sleep deprivation and sleep disorders across adolescents and adults, it is important to understand the role of sleep in alcohol toxicity to develop future therapies for prevention and treatment of alcohol-induced pathologies. UsingDrosophila melanogaster, an established model for both sleep and alcohol research, we found that acute and chronic sleep deprivation increased alcohol toxicity and eliminated long-term functional alcohol tolerance. In contrast, increased sleep prior to binge-like alcohol exposure mitigated alcohol-induced mortality even in vulnerable groups with higher susceptibility to alcohol toxicity.
Focused Ultrasound Modulation of Hepatic Neural Plexus Restores Glucose Homeostasis in Diabetes
Authors: Cotero Victoria , Miwa Hiromi , Hirschstein Zall , Qanud Khaled , Huerta Tomás S. , Tai Ningwen , Ding Yuyan , Jimenez-Cowell Kevin , Tomaio Jacquelyn-Nicole , Song Weiguo , Devarajan Alex , Tsaava Tea , Graf John , Madhavan Radhika , Wallace Kirk , Loghin Evelina , Morton Christine , Fan Ying , Kao Tzu-Jen , Akhtar Kainat , Damaraju Meghana , Barenboim Linda , Maietta Teresa , Ashe Jeffrey , Tracey Kevin J. , Coleman Thomas R. , Carlo Dino Di , Shin Damian , Zanos Stavros , Chavan Sangeeta S. , Herzog Raimund I. , Puleo Chris
Published: April 2021

While peripheral glucose sensors are known to relay signals of substrate availability to integrative nuclei in the brain, the importance of these pathways in maintaining energy homeostasis and their contribution to disease remain unknown. Herein, we demonstrate that selective activation of the hepatoportal neural plexus via transient peripheral focused ultrasound (pFUS) induces glucose homeostasis in models of well-established insulin resistant diabetes. pFUS modulates sensory projections to the hindbrain and alters hypothalamic concentrations of neurotransmitters that regulate metabolism, resulting in potentiation of hypothalamic insulin signaling, leptin-independent inhibition of the orexigenic neuropeptide Y system, and therapeutic alteration in autonomic output to peripheral effector organs. Multiomic profiling confirms pFUS-induced modifications of key metabolic functions in liver, pancreas, muscle, adipose, kidney, and intestines. Activation of the hepatic nutrient sensing pathway not only restores nervous system coordination of peripheral metabolism in three different species but does so across these organ systems; several of which are current targets of antidiabetic drug classes. These results demonstrate the potential of hepatic pFUS as a novel/non-pharmacologic therapeutic modality to restore glucose homeostasis in metabolic diseases, including type II diabetes.

One Sentence Summary

We utilize a non-invasive ultrasound technique to activate a liver-brain sensory pathway and demonstrate its potential to induce durable normalization of glucose homeostasis in models of well-established insulin resistant diabetes.
RNase L limits host and viral protein synthesis via inhibition of mRNA export
Authors: Burke James M. , Gilchrist Alison R. , Sawyer Sara L. , Parker Roy
Published: April 2021

RNase L is widely thought to limit viral protein synthesis by cleaving host rRNA and viral mRNA, resulting in translation arrest and viral mRNA degradation. Herein, we show that the mRNAs of dengue virus and influenza A virus largely escape RNase L-mediated mRNA decay, and this permits viral protein production. However, activation of RNase L arrests nuclear mRNA export, which strongly inhibits influenza A virus protein synthesis and reduces cytokine production. Importantly, the heterogeneous and temporal nature of the mRNA export block in individual cells permits sufficient production of antiviral cytokines from transcriptionally induced host mRNAs. This defines RNase L-mediated arrest of mRNA export as a key antiviral shutoff and cytokine regulatory pathway.

One Sentence Summary

RNase L-mediated shutoff of nuclear mRNA export limits viral protein synthesis and regulates antiviral cytokine production.
An Immune Cell Atlas Reveals Dynamic COVID-19 Specific Neutrophil Programming Amenable to Dexamethasone Therapy
Authors: Sinha Sarthak , Rosin Nicole L. , Arora Rohit , Labit Elodie , Jaffer Arzina , Cao Leslie , Farias Raquel , Nguyen Angela P. , de Almeida Luiz G. N. , Dufour Antoine , Bromley Amy , McDonald Braedon , Gillrie Mark , Fritzler Marvin J. , Yipp Bryan , Biernaskie Jeff
Published: April 2021

SARS-CoV-2 is a novel coronavirus that causes acute respiratory distress syndrome (ARDS), death and long-term sequelae. Innate immune cells are critical for host defense but are also the primary drivers of ARDS. The relationships between innate cellular responses in ARDS resulting from COVID-19 compared to other causes of ARDS, such as bacterial sepsis is unclear. Moreover, the beneficial effects of dexamethasone therapy during severe COVID-19 remain speculative, but understanding the mechanistic effects could improve evidence-based therapeutic interventions. To interrogate these relationships, we developed an scRNA-Seq and plasma proteomics atlas (biernaskielab.ca/COVID_neutrophil). We discovered that compared to bacterial ARDS, COVID-19 was associated with distinct neutrophil polarization characterized by either interferon (IFN) or prostaglandin (PG) active states. Neutrophils from bacterial ARDS had higher expression of antibacterial molecules such as PLAC8 and CD83. Dexamethasone therapy in COVID patients rapidly altered the IFNactivestate, downregulated interferon responsive genes, and activated IL1R2+veneutrophils. Dexamethasone also induced the emergence of immature neutrophils expressing immunosuppressive molecules ARG1 and ANXA1, which were not present in healthy controls. Moreover, dexamethasone remodeled global cellular interactions by changing neutrophils from information receivers into information providers. Importantly, male patients had higher proportions of IFNactiveneutrophils, a greater degree of steroid-induced immature neutrophil expansion, and increased mortality benefit compared to females in the dexamethasone era. Indeed, the highest proportion of IFNactiveneutrophils was associated with mortality. These results define neutrophil states unique to COVID-19 when contextualized to other life-threatening infections, thereby enhancing the relevance of our findings at the bedside. Furthermore, the molecular benefits of dexamethasone therapy are also defined, and the identified pathways and plasma proteins can now be targeted to develop improved therapeutics.
Systematic evaluation of the effect of polyadenylation signal variants on the expression of disease-associated genes
Authors: Chen Meng , Wei Ran , Wei Gang , Xu Mingqing , Su Zhixi , Zhao Chen , Ni Ting
Published: April 2021

Single nucleotide variants (SNVs) within polyadenylation signals (PASs), a specific six-nucleotide sequence required for mRNA maturation, can impair RNA-level gene expression and cause human diseases. However, there is a lack of genome-wide investigation and systematic confirmation tools for identifying PAS variants. Here, we present a computational strategy to integrate the most reliable resources for discovering distinct genomic features of PAS variants and also develop a credible and convenient experimental tool to validate the effect of PAS variants on expression of disease-associated genes. This approach will greatly accelerate the deciphering of PAS variation-related human diseases.
Ring artifact reduction via multiscale nonlocal collaborative filtering of spatially correlated noise
Authors: Mäkinen Ymir , Marchesini Stefano , Foi Alessandro
Published: April 2021

X-ray micro-tomography systems often suffer severe ring artifacts in reconstructed images. These artifacts are caused by defects in the detector, calibration errors, and fluctuations producing streak noise in the raw sinogram data. In this work, these streaks are modeled in the sinogram domain as additive stationary correlated noise upon logarithmic transformation. Based on this model, a streak removal procedure is proposed where the Block-Matching and 3-D (BM3D) filtering algorithm is applied across multiple scales, achieving state-of-the-art performance in both real and simulated data. Specifically, the proposed fully automatic procedure allows for attenuation of streak noise and the corresponding ring artifacts without creating major distortions common to other streak removal algorithms.
Restoration of plant diversity in permanent grassland by seeding: Assessing the limiting factors along land‐use gradients
Authors: Freitag Martin , Klaus Valentin H. , Bolliger Ralph , Hamer Ute , Kleinebecker Till , Prati Daniel , Schäfer Deborah , Hölzel Norbert
Published: April 2021

Land‐use intensification has caused dramatic declines in grassland biodiversity, and in Europe this decline has not yet been halted. Therefore, a major challenge in ecological restoration is to effectively restore plant diversity in permanent grasslands, that is, long‐term managed grassland not being used as cropland. As species richness is often limited by seed dispersal, introducing locally absent species is crucial. Seeding diverse seed mixtures is an appropriate tool, but restoration outcomes are highly variable. Considering constraints by land‐use intensity and plant functional traits during restoration could improve the efficacy of restoration efforts.

We established a full‐factorial experiment with high‐diversity seeding and topsoil disturbance in 73 grasslands along land‐use intensity and productivity gradients and evaluated the restoration success over 5 years. In addition, after 5 years we assessed the number of established species and tested whether specific traits promoted the establishment of sown species in interaction with productivity.

Plant diversity increased considerably when seeding and disturbance were combined while seeding alone only slightly increased species richness. Along land‐use gradients, we found no direct effects of grazing or mowing on the establishment of sown species, but fertilization indirectly limited establishment in the combined treatment via a negative effect of productivity.

Functional traits structured the establishment of sown species, especially in the combined treatments, but effects varied with productivity. Species with low seed mass and low specific leaf area had greater establishment success in low‐productivity grasslands, whereas species with high seed mass had greater establishment in high‐productivity grasslands.

Synthesis and applications. Our results highlight the potential of using diverse seed mixtures for biodiversity restoration in a wide range of permanent grasslands, especially when combined with topsoil disturbance. However, productivity both limited restoration success and affected establishment via an interaction with plant functional traits. As productivity is a major constraint in grassland restoration, we strongly recommend to first stop fertilization and reduce soil nutrient loads in highly productive grasslands. Restoration by seeding, with or without disturbance, should only be applied when productivity is reduced and the local environment should be considered to compile site‐specific seed mixtures to maximize restoration success.

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Convicted drinking and driving offenders: Comparing alcohol use before and after the pandemic outbreak
Authors: Manning Amy R. , Romano Eduardo , Diebold Josal , Nochajski Thomas H. , Taylor Eileen , Voas Robert B. , Scherer Michael
Published: April 2021

Background

Before the COVID‐19 pandemic, very little was known about the impact of social isolation on individuals’ alcohol use and misuse. This study examines how socially isolated individuals with a history of heavy drinking used alcohol during the pandemic.

Methods

Data for this study came from an add‐on to the Managing Heavy Drinking (MHD) longitudinal study of drivers convicted of DWI that was conducted in Erie County, New York. Pre‐COVID information (October 2019–March 2020) was augmented with a COVID‐19 questionnaire collected between July and August 2020. A total of 92 participants completed the COVID‐19 survey.

Results

The sample of problem drinkers showed a significant increase after the pandemic outbreak in the average number of drinking days from 1.99 to 2.49 per week (p = 0.047), but a significant decrease in the average number of drinks per drinking day, from 3.74 to 2.74 (p = 0.003). The proportion of individuals who drank more frequently was greater among those who, before the outbreak had an Alcohol Use Disorders Identification Test (AUDIT) score <8 (26% increase) compared with those with an AUDIT score of >8 (13%). Alcohol treatment was also associated with the frequency of drinking, with individuals who were not in alcohol treatment showing a 16% increase in frequency compared with a 10% increase among those in treatment. Further, individuals who, after the outbreak worried about their health (30%) or finances (37%) reported greater increases in the frequency of drinking than those who did not worry about their health (17%) or finances (10%).

Conclusions

Overall, the individuals in our sample showed small changes in the frequency andheaviness of drinking after the outbreak of COVID‐19, effects that opposite in direction from one another and thus resulted in no overall change in drinks consumed. Nonetheless, we identified factors that influenced the effects of the pandemic on drinking behavior among individuals convicted of DWI, which emphasizes the need to individualize these individuals’ treatment, particularly in the context of dramatic environmental change.
Do Remittances Promote Fertilizer Use? The Case of Ugandan Farmers
Authors: Veljanoska Stefanija
Published: April 2021

A key factor that improves agricultural productivity is land fertility. Even though the benefits from using fertilizers are well documented and widely accepted, a low level of adoption and use is observed among farmers in developing countries. According to the literature, several constraints such as lack of access to credit and insurance can explain the low level of fertilizer use among African farmers. In this paper, I investigate whether remittances have the potential to remove these constraints by promoting higher fertilizer use. In order to address this research question, I use the Ugandan Living Standards Measurement Study‐Integrated Surveys on Agriculture (LSMS‐ISA) from the World Bank. The article provides a separate analysis between organic and inorganic fertilizer, as inorganic fertilizer is riskier and more expensive than the organic options. In an instrumental variable empirical framework, I find that remittances promote fertilizer use, in particular the organic fertilizer. To unpack the mechanisms behind, the article further shows that remittances (a) induce farmers to invest in livestock and (b) act as a buffer to rainfall variability in the case of inorganic fertilize use. The results indicate that remittances can, at least partially, remove credit and insurance constraints and promote fertilizer among Ugandan farmers.
Is hepatectomy an appropriate option for bilobar liver metastasis with portal vein tumor thrombus of colorectal cancer?
Authors: Paik Kwang Yeol
Published: April 2021

The prognosis of patients with multiple liver metastasis of colorectal cancer (CLM) on both lobes accompanied by a portal vein tumor thrombus (PVTT) remains unclear. We report two patients with multiple CLM and PVTT who underwent liver resection. A 73‐year‐old man had successful extended right hemi‐hepatectomy with a thrombectomy for a macroscopic tumor thrombus in the right portal branch and multiple CLM in both lobes. At 8 months after surgery, the patient had multiple CLM in the remnant lobe with left main PVTT and died 14 months after liver surgery. A 64‐year‐old woman who had previously undergone palliative chemotherapy for adenocarcinoma of the ascending colon presented with CLM accompanied by a macroscopic tumor thrombus in the left portal branch. Tumor and PVTT had progressed despite various regimens of chemotherapy. Left hemi‐hepatectomy with radiofrequency ablation on right lobe and right hemicolectomy were performed. However, CLM occurred again within 3 months after the liver surgery. Considering these cases, a poor prognosis may be expected even though the tumor is successfully removed by liver resection.
Suitability of endobronchial ultrasound‐guided transbronchial needle aspiration samples for programmed death ligand‐1 testing in non‐small cell lung cancer, the Bristol experience
Authors: Hardy Joanna , Bhatt Nidhi , Medford Andrew R.L.
Published: April 2021

Treatment for non‐small cell lung cancer (NSCLC) is now personalised using molecular mutation testing. Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) biopsy suitability for anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutation testing is established. Less is currently known about EBUS‐TBNA suitability for PD‐L1 (programmed death ligand‐1) testing.

To assess EBUS‐TBNA biopsy adequacy for ALK, EGFR and PD‐L1 testing, we conducted a prospective study of 279 consecutive NSCLC patients referred to a tertiary EBUS‐TBNA centre in South West England. One hundred eight‐four (62.6%) patients were found to have adenocarcinoma, 83 (28.2%) had squamous cell carcinoma, and 27 (9.2%) were identified as NSCLC‐not otherwise specified. EGFR testing was successful in 166 of 168 patients (98.8%), ALK testing in all 115 and PD‐L1 testing in 43 of 49 patients (88.2%).

Previous EGFR and ALK testing did not affect biopsy PD‐L1 testing success. PD‐L1 testing failures occurred in three of five (60.0%) of 22G needle biopsies, one of five (20.0%) of 21G needle biopsies and two of 39 (5.1%) of 19G needle biopsies, P = .016.

EBUS‐TBNA biopsies are mostly suitable for PD‐L1 testing. Larger needle size may improve PD‐L1 (but not EGFR and ALK) testing success but requires further study in a controlled trial.
Price Limit Expansion and Volatility: A Theoretical Perspective*
Authors: Lee Jeong Hwan , Su Xin , Yoo Jin
Published: April 2021

We theoretically examine whether and how price limit expansion changes return volatility. This study incorporates competing hypotheses regarding investor reactions to limit‐hit events into a model that considers trader irrationality; we then conduct several simulations. We find that, when price limits are widened, stock return volatility tends to increase but may also remain unchanged or decrease. We consider the implications of the study’s main findings, which shed light on the mixed empirical results found in the price limit literature so far.
Long‐term outcomes of pulmonary metastasectomy: a multicentre analysis
Authors: Yaftian Nima , Dunne Benjamin , Antippa Phillip N. , Cheung Francis P. , Wright Gavin M.
Published: April 2021

Background

Many extrapulmonary neoplasms metastasize to the lungs. We conducted a retrospective review of all patients who underwent pulmonary metastasectomy for oligometastatic disease at two centres in order to determine long‐term outcomes.

Methods

The study institutions' thoracic surgery databases were searched for all patients who underwent pulmonary metastasectomy from 2000 to 2017.

Results

There were a total of 476 patients who underwent pulmonary metastasectomy. Mean age at time of surgery was 57.2 ± 15.9 years. Mean number of pulmonary lesions was 1.9 ± 1.6. Mean disease‐free interval (DFI) was 3.6 ± 4.3 years. The most common primary neoplasms were colorectal cancer (CRC) in 35.1% (167/476), sarcoma in 23.9% (114/476), melanoma in 16.2% (77/478), renal cell carcinoma (RCC) in 7.3% (35/476) and germ cell tumour (GCT) in 4.4% (21/476). Hospital mortality was 0.4% (2/476). Mean follow‐up time was 3.8 ± 2.9 years. Survival was 88.9% (95% confidence interval 85.77–91.5) at 1 year and 49.6% (95% confidence interval 44.4–54.6) at 5 years. On multivariate Cox‐regression analysis GCT (P = 0.004), CRC (P = 0.03), DFI of 36+ months (P = 0.007), R0 resection (P = 0.002) and non‐anatomical, sub‐lobar (wedge) resection (P = 0.002) were protective against mortality.

Conclusion

Pulmonary metastasectomy is associated with survival of 50% at 5‐year follow‐up. DFI of over 36 months, R0 resections, lesions resectable by wedge resection rather than anatomic resection and GCT and CRC primary cancers were associated with improved survival.
Impact of changing gloves during cesarean section on postoperative infective complications: A systematic review and meta‐analysis
Authors: Narice Brenda F , Almeida Joana R , Farrell Tom , Madhuvrata Priya
Published: April 2021

Introduction

The cesarean section rate around the world, currently estimated at 21.1%, continues to increase. Women who undergo a cesarean section sustain a seven‐ to ten‐fold greater risk of infective morbidity compared with those who deliver vaginally.

Material and methods

We aimed to assess the impact of changing gloves intraoperatively on post‐cesarean section infective morbidity (PROSPERO CRD42018110529). MEDLINE, Scopus, Web of Science, CINAHL, WHO Global Index Medicus, and Cochrane Central were searched for randomized controlled trials until June 2020. Published randomized controlled trials that evaluated the effects of glove changing during cesarean section on infective complications were considered eligible for the review. Two reviewers independently selected studies, assessed the risk of bias, and extracted data about interventions and adverse maternal outcomes. Dichotomous variables were presented and included in the meta‐analyses as risk ratios (RR) with 95% confidence intervals (CI). The quality of evidence was assessed using the GRADE approach in alignment with the recommendations from the Cochrane Review Group.

Results

We identified seven randomized controlled trials reporting data over 1948 women. Changing gloves during a cesarean section was associated with a statistically significantly lower incidence of wound infective complications (RR 0.41, 95% CI 0.26–0.65, p < 0.0001; GRADE moderate quality evidence). This intervention seemed to be effective only if performed after delivery of the placenta. No significant difference was seen in the incidence of endometritis (RR 0.96, 95% CI 0.78–1.20, p = 0.74; GRADE moderate quality evidence) and/or febrile morbidity (RR 0.73, 95% CI 0.30–1.81, p = 0.50; GRADE moderate quality evidence), regardless of the timing of the intervention.

Conclusions

Changing gloves after delivery of the placenta during a cesarean section is associated with a significant reduction in the incidence of post‐surgical wound complications compared with keeping the same gloves throughout the whole surgery. However, an adequately powered study to assess the limitations and cost‐effectiveness of the intervention is needed before this recommendation can be translated into current clinical practice.