bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral economics of cocaine self-administration in male and female rats
Authors: Sun WenLin , Yuill Matthew B. , Fan Meiyun
Published: October 2020

There are sex differences in the development of cocaine addiction. For example, the time that it takes for women from initial use to addiction is significantly shorter than for men. Thus, understanding why females are more vulnerable to cocaine addiction will provide insights into sex differences in the mechanisms underlying cocaine addiction. This study aimed to determine how cocaine demand intensity and elasticity might differ between sexes. In addition, the impact of estrous cycle and cocaine intake on demand was investigated. Male and female rats were trained to self-administer 0.125 mg of cocaine intravenously under a chained schedule in daily 2-h sessions for 2 weeks, and then, the cocaine demand function was determined with a modified within-session threshold procedure. Following the test, the rats began to self-administer a higher dose of cocaine (0.25 mg) to increase the cocaine intake. The demand function was then similarly determined in the same rats after 2 weeks of cocaine self-administration of the higher dose. No sex differences were found in either demand intensity or elasticity. Neither did the level of cocaine intake have an impact on demand. The demand elasticity, but not intensity, was significantly lower during proestrus/estrus compared with diestrus. These data suggest that the faster transition to cocaine addiction in women cannot be explained by sex differences in the demand for cocaine and such a demand may change during different phases of estrus cycle.
Glibenclamide treatment prevents depressive-like behavior and memory impairment induced by chronic unpredictable stress in female mice
Authors: Rosado Axel Fogaça , Rosa Priscila Batista , Platt Nicolle , Pierone Bruna Caroline , Neis Vivian Binder , Severo Rodrigues Ana Lúcia , Kaster Manuella Pinto , Kaufmann Fernanda Neutzling
Published: October 2020

Glibenclamide is a second-generation sulfonylurea used in the treatment of Type 2 Diabetes Mellitus. The primary target of glibenclamide is ATP-sensitive potassium channels inhibition; however, other possible targets include the control of inflammation and blood–brain barrier permeability, which makes this compound potentially interesting for the management of brain-related disorders. Here, we showed that systemic treatment with glibenclamide (5 mg/kg, p.o., for 21 days) could prevent the behavioral despair and the cognitive dysfunction induced by chronic unpredictable stress (CUS) in mice. In nonhypoglycemic doses, glibenclamide attenuated the stress-induced weight loss, decreased adrenal weight, and prevented the increase in glucocorticoid receptors in the prefrontal cortex, suggesting an impact in hypothalamic–pituitary–adrenal (HPA) axis function. Additionally, we did not observe changes in Iba-1, NLRP3 and caspase-1 levels in the prefrontal cortex or hippocampus after CUS or glibenclamide treatment. Thus, this study suggests that chronic treatment with glibenclamide prevents the emotional and cognitive effects of chronic stress in female mice. On the other hand, the control of neuroinflammation and NLRP3 inflammasome pathway is not the major mechanism mediating these effects. The behavioral effects might be mediated, in part, by the normalization of glucocorticoid receptors and HPA axis.
Intraoperative systemic biomarkers predict post-liver transplantation acute kidney injury
Authors: Cezar Lia Cavalcante , Meneses Gdayllon Cavalcante , da Silva Junior Geraldo Bezerra , Bezerra Gabriela Freire , Martins Alice Maria Costa , Libório Alexandre Braga , Daher Elizabeth De Francesco , Garcia José Huygens Parente
Published: October 2020

Objective

Liver transplant (LT) is a definitive therapeutic option for patients with chronic liver disease. However, acute kidney injury after LT (post-LT AKI) is a frequent complication that may lead to graft dysfunction and decrease life expectancy. Delay in AKI detection by traditional biomarkers boosted research with new biomarkers for post-LT AKI as neutrophil gelatinase-associated lipocalin (NGAL) and syndecan-1. We aim to evaluate associations of intraoperative systemic NGAL and syndecan-1 levels with post-LT AKI.

Methods

This is a prospective study conducted in 46 patients selected for LT. Patients were evaluated preoperatively and blood samples were collected intraoperatively: T1 (after induction of anesthesia), T2 (anhepatic phase) and T3 (2 h after reperfusion of the graft).

Results

The mean age was 54 ± 12 years and 60% were male. Post-LT AKI was observed in 24 (52%) patients of which 12% needed dialysis. Serum NGAL and syndecan-1 increased along surgical phases. Mostly, increment values of serum NGAL of T2 to T3 and syndecan-1 at T3 were importantly associated with post-LT AKI. Into a multivariate model with model for end-stage liver disease score, age, gender, warm ischemia, cold ischemia and surgery time, syndecan-1 levels at T3 remains capable to predict post-LT AKI. Serum NGAL had significance only with increment values calculated by the ratio of ‘T3/T2’. Finally, serum syndecan-1 at T3 had a better diagnostic performance in receiver operating characteristic curve analysis.

Conclusion

Serum syndecan-1 levels in 2 h after reperfusion were most useful in early post-LT AKI diagnosis and may be used to construct new risk groups in this context.
A prospective cohort study of the use of the fatty liver index and Fibroscan to determine the prevalence of fatty liver disease in an Irish population
Authors: Rabbitt Louise A. , McNally Mairéad , Reynolds Laura , Hinchion Kate , Simpkin Andrew , Scarry Margaret , Bohan-Keane Mary , Goulding Carol
Published: October 2020

Objectives

Rates of nonalcoholic fatty liver disease (NAFLD) are increasing worldwide. The fatty liver index (FLI) is a noninvasive predictor of NAFLD. This prospective cohort study used the FLI to estimate the prevalence of NAFLD in patients attending an Irish Acute Medical Unit (AMU), and assessed the degree of fibrosis in this group using Fibroscan.

Methods

Patients attending the AMU over a 3-month period were invited to participate. Patients with excess alcohol consumption or pre-existing liver disease were excluded. Using established FLI cut-offs, 414 participants were grouped into low (FLI ≤ 30), medium (30 < FLI ≤ 60) and high (FLI > 60) risk of NAFLD. High-risk patients were offered review including liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) score.

Results

A total of 134 patients were at low-risk, 96 at medium-risk and 184 at high-risk of NAFLD. Male sex (P < 0.0001) and increasing age (P < 0.0001) were associated with higher risk. Of the 120 high-risk patients who attended follow up, 13 participants had LSM > 7 kPa. Higher FLI scores were associated with higher CAP scores (P < 0.0001) but did not predict higher LSMs. Fasting glucose and HbA1c were found to be associated with higher LSM.

Conclusion

About 44.4% of patients presenting to the AMU were at high risk of NAFLD according to the FLI. Only 10.8% of the high-risk group, and 3% of all those recruited had a LSM > 7 kPa suggesting development of fibrosis.
Deep learning enabled classification of Mayo endoscopic subscore in patients with ulcerative colitis
Authors: Bhambhvani Hriday P. , Zamora Alvaro
Published: October 2020

Objective

Previous reports of deep learning-assisted assessment of Mayo endoscopic subscore (MES) in ulcerative colitis have only explored the ability to distinguish disease remission (MES 0/1) from severe disease (MES 2/3) or inactive disease (MES 0) from active disease (MES 1–3). We sought to explore the utility of deep learning models in the automated grading of each individual MES in ulcerative colitis.

Methods

In this retrospective study, a total of 777 representative still images of endoscopies from 777 patients with clinically active ulcerative colitis were graded using the MES by two physicians. Each image was assigned an MES of 1, 2, or 3. A 101-layer convolutional neural network model was trained and validated on 90% of the data, while 10% was left for a holdout test set. Model discrimination was assessed by calculating the area under the curve (AUC) of a receiver operating characteristic as well as standard measures of accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV).

Results

In the holdout test set, the final model classified MES 3 disease with an AUC of 0.96, MES 2 disease with an AUC of 0.86, and MES 1 disease with an AUC 0.89. Overall accuracy was 77.2%. Across MES 1, 2, and 3, average specificity was 85.7%, average sensitivity was 72.4%, average PPV was 77.7%, and the average NPV was 87.0%.

Conclusion

We have demonstrated a deep learning model was able to robustly classify individual grades of endoscopic disease severity among patients with ulcerative colitis.
Decreased number of colonic tuft cells in quiescent ulcerative colitis patients
Authors: Kjærgaard Sebastian , Jensen Thorbjørn S.R. , Feddersen Ulrike R. , Bindslev Niels , Grunddal Kaare V. , Poulsen Steen S. , Rasmussen Hanne B. , Budtz-Jørgensen Esben , Berner-Hansen Mark
Published: October 2020

Background

Colonic tuft cells are epithelial chemosensory cells involved in barrier integrity, modulation of inflammatory responses and gut homeostasis. Recent evidence indicates an involvement of tuft cells in ulcerative colitis pathogenesis, though mechanisms remain largely unknown.

Here, we quantified the colonic tuft cell population in patients with quiescent ulcerative colitis as compared to patients without identified colonic disease (controls).

Methods

In this retrospective study, we obtained endoscopic colonic sigmoid biopsies from 14 patients with quiescent ulcerative colitis and from 17 controls. In a blinded central-reading design, we identified tuft cells by immunohistochemistry using a cyclooxygenase-1 antibody as a marker and performed a simple counting by visual inspection. Poisson regression was employed for statistics and results were adjusted for gender, age and smoking status.

Results

Ulcerative colitis patients demonstrated a 55% reduced tuft cell count in colonic mucosa compared with the control group (95% confidence limit: range 31–71%, P = 0.0002). Ulcerative colitis patients had a mean tuft cells count of 46 tuft cells/mm2 (95% CI, 36–59), while controls demonstrated a mean of 104 tuft cells/mm2 (95% CI, 79–136). No interactions of other covariates, such as age, smoking status, total duration of ulcerative colitis disease and duration of clinical remission prior to study inclusion were detected between ulcerative colitis patients and controls.

Conclusion

Quiescent ulcerative colitis patients have a relatively low number of colonic tuft cells. Further studies are warranted to explore the potential involvement of tuft cells in ulcerative colitis pathogenesis.
P53 is a risk factor of de-novo hepatitis C-related hepatocellular carcinoma treated with direct-acting antivirals: a case-control study
Authors: Omran Mohamed , Fouda Manar , Abdelwahab Abdelwahab Osama , Nabeel Mohamed Mahmoud , Abdelaziz Ashraf Omar , Omran Dalia , Shousha Hend Ibrahim
Published: October 2020

Background

The mechanisms underlying de-novo hepatocellular carcinoma (HCC) after direct-acting antivirals (DAAs) is still under investigation. This work aims to study P53 and hepatocyte growth factor (HGF) as possible diagnostics of de-novo hepatocellular carcinoma (HCC) following DAAs in comparison to alpha-fetoprotein (AFP).

Method

This case-control study included 166 patients with liver cirrhosis divided into group-1: patients without HCC (n = 50), group-2: patients with de-novo HCC following DAAs, and achieved sustained virological response (n = 50), and group-3: patients with HCC without DAAs (n = 66). P53 antibody and HGF were determined using a quantitative sandwich enzyme immunoassay technique (Cusabio Co, Houston, USA).

Results

Patients with HCC showed significantly higher HGF. Patients with de-novo HCC following DAAs had significantly higher P53 than HCC without DAAs (P < 0.0001). The multiple logistic regression analysis showed that the P53 levels were significantly associated with susceptibility to de-novo HCC (P value = 0.004). The best overall formula was constructed for HCC diagnosis by entering significant markers into the regression model. A three markers model was developed = (1.22 + AFP X 0.002 + HGF X 0.001 + P53 X 0.001). The medians (percentiles) of combined three markers were 1.8 (1.0–2.1) in liver cirrhosis and 2.2 (2.0–2.9) in all HCC (P < 0.00001). The AUC of combined markers was greater than a single marker. The AUC was 0.87 to differentiate HCC from liver cirrhosis; AUC 0.91 to differentiate de-novo HCC after DAAs from liver cirrhosis.

Conclusion

P53 may serve as a diagnostic marker for de-novo HCC after DAAs therapy. HGF may serve as a diagnostic marker for HCC but not specific for de-novo HCC after DAAs therapy.
Effect of oxygen supply on mortality in acute ST-elevation myocardial infarction: systematic review and meta-analysis
Authors: Alves Mariana , Prada Luísa , Costa João , Ferreira Joaquim J. , Pinto Fausto J. , Caldeira Daniel
Published: October 2020

Previous studies stated that high oxygen supply in patients with myocardial infarction (MI) was not associated with improved outcomes. However, the particularities of ST-elevation myocardial infarction (STEMI) and the results of a recent trial raised the question if this subgroup of patients benefits from high oxygen supply. This study aims to evaluate the clinical effect of high oxygen supply in patients with STEMI using a systematic review of the available literature. All randomized controlled trials (RCTs) evaluating the systematic use of high oxygen (6 L/min or higher) versus room air or lower oxygen supply in STEMI patients were included. Systematic review with meta-analysis of trials retrieved in July 2020. Six databases were searched. The confidence in the pooled estimates was ascertained through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Risk of bias was evaluated using the Cochrane risk of bias tool. There were five eligible RCTs (7703 patients). High oxygen supply was associated with a significant risk reduction of short-term mortality [risk ratio (RR) 0.83; 95% confidence interval (CI), 0.70–0.98; I
2 = 0%]. Mortality (longest follow-up) (RR 0.83; 95% CI, 0.71–0.97; I
2 = 0%) and heart failure (RR 0.84; 95% CI, 0.60–1.18; I
2 = 0%) did not present a risk reduction. Recurrent MI presented a contradictory result, favouring the lower oxygen protocol (RR 1.47; 95% CI, 0.84–2.56; I
2 = 0%). The GRADE analysis was very low. High oxygen supply may be associated with a decrease in short-term mortality in STEMI patients, but the pooled data are not robust enough to allow definitive conclusions.
Sepsis in Home Health Care
Authors: Chimenti Chris , Sears Geralyn , McIntyre Jack
Published: October 2020

Background:

A majority of sepsis cases originate in the home and community. Home health clinicians play an important role in the early identification and timely treatment of sepsis.

Local Problem:

A home health care provider sought to prevent hospital readmissions due to sepsis by implementing a sepsis-screening protocol and quality improvement initiative.

Methods:

The provider conducted a retrospective chart review of 33 264 sepsis screens of 7242 patients.

Interventions:

A sepsis-screening protocol, clinician and patient/caregiver sepsis education, physician and emergency department communication, and emergency medical services collaboration procedure were implemented.

Results:

A majority (69.2%) of positive sepsis screens resulted in patients receiving early medical intervention and avoiding hospitalization.

Conclusions:

Having a formal sepsis-screening program in place prompts home health clinicians to communicate the patient's symptoms to their primary care provider, which can positively impact hospital readmission rates and associated medical costs.
Psychosocial Work Factors of the Job Strain Model and All-Cause Mortality: The STRESSJEM Prospective Cohort Study
Authors: Niedhammer Isabelle , Milner Allison , Coutrot Thomas , Geoffroy-Perez Béatrice , LaMontagne Anthony D. , Chastang Jean-François
Published: October 2020

Objective

The objectives were to examine the prospective associations between psychosocial work factors of the job strain model and all-cause mortality in a national representative cohort of French employees using various measures of time-varying exposure.

Methods

The study was based on a sample of 798,547 men and 697,785 women for which data on job history from 1976 to 2002 were linked to mortality data from the national death registry. Psychosocial work factors from the validated job strain model questionnaire were imputed using a job-exposure matrix. Three time-varying measures of exposure were explored: current, cumulative, and recency-weighted cumulative exposure. Cox proportional hazards models were performed to study the associations between psychosocial work factors and mortality.

Results

Within the 1976–2002 period, 88,521 deaths occurred among men and 28,921 among women. Low decision latitude, low social support, job strain, isostrain, high strain, and passive job were found to be risk factors for mortality. The model using current exposure was the best relative-quality model. The associations of current exposure to job strain and mortality were found to have hazard ratios of 1.30 (95% confidence interval [CI] = 1.24–1.36) among men and 1.15 (95% CI = 1.06–1.25) among women. The population fractions of mortality attributable to job strain were 5.64% (95% CI = 4.56%–6.71%) among men and 4.13% (95% CI = 1.69%–6.71%) among women.

Conclusions

This study supports the role of the psychosocial work factors of the job strain model on all-cause mortality. Preventive intervention to improve the psychosocial work environment may help to prevent mortality in working populations.
Interventions to Improve HIV Care Continuum Outcomes Among Individuals Released From Prison or Jail: Systematic Literature Review
Authors: Woznica Daniel M. , Fernando Nimasha B. , Bonomo Elizabeth J. , Owczarzak Jill , Zack Barry , Hoffmann Christopher J.
Published: October 2020

Background:

HIV care continuum outcomes deteriorate among people returning from incarceration. Interventions to improve care outcomes postincarceration have been characterized by substantial heterogeneity in approach, outcome metrics, and results. A large number of recently published interventions have not been systematically reviewed.

Methods:

We searched peer reviewed and scholarly databases for published and gray literature describing interventions to improve HIV care continuum outcomes among individuals released from prison or jail. We systematically screened quantitative and qualitative intervention reports published through 2018, then extracted and analyzed study data using a classification scheme that we developed for categorizing intervention levels and strategies.

Results:

We included 23 reports from the peer-reviewed literature, 2 from gray literature, and 2 from conference abstracts (27 total). Seventeen studies were classified as individual level, 3 as biomedical level, 2 as organizational level, and 5 as multilevel. Nine studies were randomized controlled trials, 4 of which reported power calculations. Fifteen studies were quasiexperimental; one was a case study. Eleven studies were conducted in prisons, 7 in jails, and 9 in both prisons and jails. Of 11 studies reporting hypothesis tests, 5 found statistically significant effect sizes on primary outcomes.

Conclusions:

Interventions that demonstrate postrelease improvements in clinic attendance and viral suppression include patient navigation strategies, especially involving peer support, and substance use treatment strategies.
Effectiveness and Safety of Interferon-Free Direct-Acting Antiviral Hepatitis C Virus Therapy in HIV/Hepatitis C Virus Coinfected Individuals: Results From a Pan-European Study
Authors: Amele Sarah , Peters Lars , Rodger Alison , Lundgren Jens , Rockstroh Jurgen , Matulionyte Raimonda , Leen Clifford , Jabłonowska Elzbieta , Østergaard Lars , Bhagani Sanjay , Sarcletti Mario , Clarke Amanda , Falconer Karolin , Wandeler Gilles , Domingo Pere , Maltez Fernando , Zaccarelli Mauro , Chkhartisvili Nikoloz , Szlavik Janos , Stephan Christoph , Fonquernie Laurent , Aho Inka , Mocroft Amanda ,   on behalf of the EuroSIDA study group
Published: October 2020

Objectives:

To investigate the effectiveness, safety, and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/hepatitis C virus (HCV) coinfected individuals in Europe.

Methods:

All HIV/HCV coinfected individuals in the EuroSIDA study that started interferon free DAA treatment between January 6, 2014, and January 3, 2018, with ≥12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result ≥12 weeks after stopping treatment (SVR12). Logistic regression was used to explore factors associated with SVR12.

Results:

1042 individuals started interferon-free DAA treatment after 1/6/2014 and were included, 862 (82.2%) had a known response to treatment, and 789 [91.5%, 95% confidence interval (CI): 89.7 to 93.4] of which achieved SVR12. There were no differences in SVR12 across regions of Europe (P = 0.84). After adjustment, the odds of achieving SVR12 was lower in individuals that received sofosbuvir/simeprevir ± ribavirin (RBV) [adjusted odds ratio 0.21 (95% CI: 0.08 to 0.53)] or ombitasvir/paritaprevir/dasabuvir ± RBV [adjusted odds ratio 0.46 (95% CI: 0.22 to 1.00)] compared with sofosbuvir/ledipasvir ± RBV. Forty-three (4.6%) individuals had one or more components of their HCV regimen stopped early, most commonly because of toxicity (n = 14); of these 14, 11 were treated with ribavirin. Increased bilirubin was the most common grade 3 or 4 laboratory adverse event (n = 15.3%) and was related to treatment with atazanavir and ribavirin.

Conclusions:

Our findings from real-world data on HIV/HCV coinfected individuals across Europe show DAA treatment is well tolerated and that high rates of SVR12 can be achieved in all regions of Europe.
Marinobacter halodurans sp. nov., a halophilic bacterium isolated from sediment of a salt flat
Authors: Yoo Yeonjae , Lee Hanbyul , Kwon Bong-Oh , Khim Jong Seong , Baek Seungwoo , Pathiraja Duleepa , Park Byeonghyeok , Choi In-Geol , Kim Gyu-Hyeok , Kim Beom Seok , Kim Jae-Jin
Published: October 2020

A Gram-staining-negative, aerobic, cream-coloured, marine bacterium, with rod-shaped cells, designated strain YJ-S3-2T, was isolated from salt flat sediment of Yongyu-do, Republic of Korea. YJ-S3-2T grew at pH 5.0–9.0 (optimum pH 7.0), 4–45 °C (optimum 30 °C) and with 1–18 % (w/v) NaCl (optimum 6 %). The results of 16S rRNA gene sequence analysis indicated that YJ-S3-2T was closely related to

Marinobacter segnicrescens

SS011B1-4T (97.0 %) followed by, '

Marinobacter nanhaiticus

' D15-8W (96.7 %),

Marinobacter bryozoorum

50-11T (96.7 %),

Marinobacter koreensis

DSMZ 179240T T (96.5 %) and

Marinobacter bohaiensis

T17T (96.5 %). The average nucleotide identity (ANI) and the genome to genome distance calculator (GGDC) estimate values between YJ-S3-2T and related type strains were 73.7–79.8 and 19.9–22.5 %, and also 73.5 and 20.7 % with

Marinobacter hydrocarbonoclasticus

. YJ-S3-2T was characterized as having Q-9 as the predominant respiratory quinone and the principal fatty acids (>10 %) were C16 : 0 (22.3 %), summed feature 9 (C17 : 1iso ω9c/C16 : 0 10-methyl, 13.8 %) and 3 (C16 : 1ω7c/C16 : 1ω6c, 11.9 %). The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids and two unidentified phospholipids. The DNA G+C content of YJ-S3-2T is 60.9 mol%. On the basis of the polyphasic taxonomic evidence presented in this study, YJ-S3-2T should be classified as representing a novel species within the genus

Marinobacter

, for which name Marinobacter halodurans sp. nov. is proposed, with the type strain YJ-S3-2T (=KACC 19883T=KCTC 62937T=JCM 33109T).
A Sensitive, Rapid, and Portable CasRx-based Diagnostic Assay for SARS-CoV-2
Authors: Brogan Daniel J , Chaverra-Rodriguez Duverney , Lin Calvin P , Smidler Andrea L , Yang Ting , Alcantara Lenissa M. , Antoshechkin Igor , Liu Junru , Raban Robyn R , Belda-Ferre Pedro , Knight Rob , Komives Elizabeth A , Akbari Omar S.
Published: October 2020

Since its first emergence from China in late 2019, the SARS-CoV-2 virus has spread globally despite unprecedented containment efforts, resulting in a catastrophic worldwide pandemic. Successful identification and isolation of infected individuals can drastically curtail virus spread and limit outbreaks. However, during the early stages of global transmission, point-of-care diagnostics were largely unavailable and continue to remain difficult to procure, greatly inhibiting public health efforts to mitigate spread. Furthermore, the most prevalent testing kits rely on reagent- and time-intensive protocols to detect viral RNA, preventing rapid and cost-effective diagnosis. Therefore the development of an extensive toolkit for point-of-care diagnostics that is expeditiously adaptable to new emerging pathogens is of critical public health importance. Recently, a number of novel CRISPR-based diagnostics have been developed to detect COVID-19. Herein, we outline the development of a CRISPR-based nucleic acid molecular diagnostic utilizing a Cas13d ribonuclease derived from Ruminococcus flavefaciens (CasRx) to detect SARS-CoV-2, an approach we term SENSR (Sensitive Enzymatic Nucleic-acid Sequence Reporter). We demonstrate SENSR robustly detects SARS-CoV-2 sequences in both synthetic and patient-derived samples by lateral flow and fluorescence, thus expanding the available point-of-care diagnostics to combat current and future pandemics.
Characteristics and evolution of COVID-19 cases in Brazil: mathematical modeling and simulation
Authors: Cardoso Passos Carlos Augusto , Vieira Estéfano Aparecido , Lourenço José André , do Nascimento Jefferson Oliveira
Published: October 2020

The pandemic caused by the coronavirus of severe acute respiratory syndrome 2 (SARS-CoV-2), the etiological agent of the 2019 coronavirus disease (COVID-19), represents a threat of great magnitude not faced in this century. As a result, each government has proposed emergency public health measures that are critical to delay the transmission and spread of the virus and mitigate its impacts. In Brazil, the outbreak triggered many cases of people infected with COVID-19. Considering there are no drugs or vaccines proven to be effective to treat the disease, analyzing the data of infection cases and their mathematical interpretation are essential for supporting and guiding governmental measures to suppress and mitigate the impact of COVID-19. This means that estimates with mathematical models to assess the development potential of sustained human-human transmission are needed. Since the disease has its own biological characteristics, the models need to be adapted to the variability of the regions’ characteristics and the decision-making by both the government and the population, in order to be able to deal with real situations. Thus, in the present paper, we analyzed the official data of COVID-19 in Brazil and used the Johnson-Mehl-Avrami-Kolmogorov (JMAK) equation to predict the evolution of the disease. The model indicates that a nucleation rate is of fourth order, which indicates that Brazilians are crowding with no respect to measures of social distance and disease prevention. In our opinion, the political authorities were unable to control the spread of the disease in Brazil, given that social mobility was interrupted by the federal and state governments.
Integration of Kalman filter in the epidemiological model: a robust approach to predict COVID-19 outbreak in Bangladesh
Authors: Islam Md. Shariful , Hoque Md. Enamul , Amin Mohammad Ruhul
Published: October 2020

As one of the most densely populated countries in the world, Bangladesh have been trying to contain the impact of a pandemic like COVID-19 since March, 2020. Although government announced an array of restricted measures to slow down the diffusion in the beginning of the pandemic, the lockdown has been lifted gradually by reopening all the industries, markets and offices with a notable exception of educational institutes. As the physical geography of Bangladesh is highly variable across the largest delta, the population of different regions and their lifestyle also differ in the country. Thus, to get the real scenario of the current pandemic across Bangladesh, it is essential to analyze the transmission dynamics over the individual districts. In this article, we propose to integrate the Unscented Kalman Filter (UKF) with classic SIRD model to explain the epidemic evolution of individual districts in the country. We show that UKF-SIRD model results in a robust prediction of the transmission dynamics for 1-4 months. Then we apply the robust UKF-SIRD model over different regions in Bangladesh to estimates the course of the epidemic. Our analysis demonstrate that in addition to the densely populated areas, industrial areas and popular tourist spots are in the risk of higher COVID-19 transmission. In the light of these outcomes, we provide a set of suggestions to contain the pandemic in Bangladesh. All the data and relevant codebase is available athttps://mjonyh.github.io.

Highlights

We integrate the UKF with classic SIRD model for the better estimation of the COVID-19 diffusion of 64 districts in Bangladesh.

Nationwide analysis show the strong correlation between population density and the number of COVID-19 positive cases in the country.

Industrial zones and popular tourists spots are at greater risk of spreading the Coronavirus.

With the better assessment of the COVID-19 cases dynamics, the Government will find effective policies to contain the current pandemic.
The timeout procedure in pediatric surgery - effective tool or lip service? A randomized prospective observational study
Authors: Muensterer Oliver J. , Kreutz Hendrik , Poplawski Alicia , Goedeke Jan
Published: October 2020

Background

For over a decade, the preoperative timeout procedure has been implemented in most pediatric surgery units. In our hospital, a standardized team-timeout is performed before every operation. However, the impact of this intervention has not been systematically studied.

Purpose

This study evaluates whether purposefully-introduced errors during the timeout routine are picked up by the operating team members.

Methods

After ethics board approval and informed consent, deliberate errors were randomly and clandestinely introduced into the timeout routine for elective surgical procedures by a pediatric surgery attending. Errors were randomly selected among wrong name, site, side, allergy, intervention, birthdate, and gender items. The main outcome measure was how frequent an error was picked up by the team, and by whom.

Results

Over the course of 16 months, 1800 operations and timeouts were performed. Errors were randomly introduced in 120 cases (6.7%). Overall, 54% of the errors were picked up, the remainder went unnoticed. Errors were picked up most frequently by an anesthesiologists (64%), followed by nursing staff (28%), residents-in-training (6%) and medical students (1%).

Conclusions

Errors in the timeout routine go unnoticed by the team in almost half of cases. Therefore, even if preoperative timeout routines are strictly implemented, mistakes may be overlooked. Hence, the timeout procedure in its current form appears unreliable. Future developments may be useful to improve the quality of the surgical timeout and should be studied in detail.
Systemic immune mediators predict therapeutic response and tumor-infiltrating lymphocyte intensity in triple-negative breast cancer
Authors: Lopes Ananda D. , Galdino Nayane A.L. , Figueiredo Amanda B. , Brianese Rafael C. , Morais Katia L.P. , De Brot Marina , A.B.T Cynthia , Osório  , Teixeira-Carvalho Andrea , Calsavara Vinicius F. , Evangelista Guilherme F.B. , Alves Natalia S. , Makdissi Fabiana B. , Sanches Solange M. , Cordeiro de Lima Vladmir C. , Carraro Dirce M. , Gollob Kenneth J.
Published: October 2020

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer defined by the lack of expression of estrogen receptor, progesterone receptors, and of the human epithelial growth factor receptor 2. Neoadjuvant chemotherapy has proven efficacy in the treatment of TNBC, and a pathological complete response (pCR) is predictive of improved long-term survival. The immune response exerts a vital role in response to neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumor-infiltrating lymphocytes (TILs) in pre-treated tumor tissue samples and the likelihood of achieving pCR. Despite this, the relationship between the systemic immune response and the tumor microenvironment is unclear. In this prospective study, we determined the systemic plasma immune profile of TNBC patients before treatment using a panel of 27 immune mediators and measured the percentage of TILs from the same patients. Patients who demonstrated pCR had significantly higher systemic immune mediators; GM-CSF, FGF-basic, VEGF, IL-2, and IL-5, than the non-responders. Moreover, responders displayed a strong positive correlation between the cytokines IFN-γ and IL-7 with the percentage of TILs, while non-responders had a negative or no correlation. Finally, systemic immune mediator levels before treatment predict pCR (AUC range 0.64 - 0.71), and the combination of immune mediators and TILs improved pCR prediction (AUC 0.71 - 0.82). In conclusion, increased systemic immune mediators reflect increased TILs percentage and act as potential predictive biomarkers of pCR for TNBC patients submitted to neoadjuvant chemotherapy.
A phenome-wide multi-directional Mendelian randomization analysis of atrial fibrillation
Authors: Wang Qin , Richardson Tom G , Sanderson Eleanor , Ala-Korpela Mika , Smith George Davey , Holmes Michael V
Published: October 2020

Background

The prevalence of atrial fibrillation (AF) is increasing with an aging worldwide population, yet a comprehensive understanding of its causes and consequences remains limited.

Objectives

To assess the causes and consequences of AF via a multi-directional Mendelian randomization (MR) analysis scanning thousands of traits in a hypothesis-free approach.

Methods

We used publicly available GWAS data centralised and harmonised by the IEU open GWAS database. We assessed the potential causal role of 5048 exposures on risk of AF and the causal role of genetic liability to AF on 10,308 outcomes via two-sample MR analysis. Multivariable MR analysis was further conducted to explore the comparative role of identified risk factors.

Results

MR analysis suggested that 55 out of 5048 exposure traits, including four proteins, play a causal role in AF (P < 1e-5 allowing for multiple comparisons). Multivariable analysis suggested that higher body mass index, height, systolic blood pressure as well as genetic liability to coronary artery diseases independently cause AF. Three out of the four proteins (DUSP13, TNFSF12 and IL6R) had a drug prioritising score for atrial fibrillation of 0.26, 0.38 and 0.88, respectively (values closer to 1 indicating stronger evidence of the protein as a potential drug target). Genetic liability to AF was linked to a higher risk of cardioembolic ischemic stroke.

Conclusions

Body mass index, height, systolic blood pressure and genetic liability to coronary artery diseases are independent causal risk factors for AF. Several proteins including DUSP13, IL-6R and TNFSF12 may represent therapeutic potential for preventing AF.
Individuals with recurrent low back pain exhibit further altered trunk control in remission than when in pain
Authors: Shih Hai-Jung Steffi , Van Dillen Linda , Kutch Jason , Kulig Kornelia
Published: October 2020

Background

Movement alterations due to low back pain (LBP) could lead to long-term adverse consequences if they do not resolve after symptom subsides. This study aims to determine if altered trunk control associated with recurrent low back pain persists beyond symptom duration.

Methods

Twenty young adults with recurrent low back pain were tested once during an LBP episode and once in symptom remission, and twenty matched back-healthy participants served as controls. Participants walked on a treadmill with five prescribed step widths. Motion capture and surface electromyography were used to record frontal plane trunk kinematics and muscle activation. Thorax-pelvis coordination was calculated using vector coding technique, and bilateral longissimus activation and co-activation were analyzed.

Findings

Young adults with recurrent LBP exhibited a “looser” trunk control strategy in the frontal plane during gait that was persistent regardless of pain status across multiple step widths compared to back-healthy controls. This was demonstrated by a greater pelvis-only, less thorax-only coordination pattern, and decreased bilateral longissimus co-activation in individuals with recurrent LBP than controls. The looser trunk control strategy was further amplified when individuals with recurrent LBP were in symptom remission and exhibited greater trunk excursion and reduced in-phase coordination.

Interpretation

The amplification of aberrant movement during symptom remission may suggest that movement patterns or anatomical factors existing prior to the tested painful episode underlie the altered trunk control in individuals with recurrent LBP. The symptom remission period of recurrent LBP patients may be a critical window into clinical evaluation and treatment.
A Comparative Analysis of System Features Used in the TREC-COVID Information Retrieval Challenge
Authors: Chen Jimmy , Hersh William R.
Published: October 2020

The COVID-19 pandemic has resulted in a rapidly growing quantity of scientific publications from journal articles, preprints, and other sources. The TREC-COVID Challenge was created to evaluate information retrieval methods and systems for this quickly expanding corpus. Based on the COVID-19 Open Research Dataset (CORD-19), several dozen research teams participated in over 5 rounds of the TREC-COVID Challenge. While previous work has compared IR techniques used on other test collections, there are no studies that have analyzed the methods used by participants in the TREC-COVID Challenge. We manually reviewed team run reports from Rounds 2 and 5, extracted features from the documented methodologies, and used a univariate and multivariate regression-based analysis to identify features associated with higher retrieval performance. We observed that fine-tuning datasets with relevance judgments, MS-MARCO, and CORD-19 document vectors was associated with improved performance in Round 2 but not in Round 5. Though the relatively decreased heterogeneity of runs in Round 5 may explain the lack of significance in that round, fine-tuning has been found to improve search performance in previous challenge evaluations by improving a system’s ability to map relevant queries and phrases to documents. Furthermore, term expansion was associated with improvement in system performance, and the use of the narrative field in the TREC-COVID topics was associated with decreased system performance in both rounds. These findings emphasize the need for clear queries in search. While our study has some limitations in its generalizability and scope of techniques analyzed, we identified some IR techniques that may be useful in building search systems for COVID-19 using the TREC-COVID test collections.
Informal coercion during childbirth: risk factors and prevalence estimates from a nationwide survey among women in Switzerland
Authors: Oelhafen Stephan , Trachsel Manuel , Monteverde Settimio , Raio Luigi , Müller Eva Cignacco
Published: October 2020

Background

In many countries, the increase in facility births is accompanied by a high rate of obstetric interventions. Lower birthrates or elevated risk factors such as women’s higher age at childbirth and thus a higher need for control and security cannot entirely explain this rise in obstetric interventions. Another potential factor is that women feel coerced to agree to interventions; however, the prevalence of coercive interventions is unknown.

Methods

In a nationwide cross-sectional online survey, we assessed mothers’ satisfaction with childbirth and the prevalence of informal coercion during childbirth and of women at risk for postpartum depression. We used multivariable logistic regression to estimate the risk associated with multiple individual and contextual factors. Women at least 18 years old who gave birth in Switzerland within the previous 12 months were recruited online via Facebook ads or offline via various channels.

Results

A total of 6’054 women completed the questionnaire (drop-out rate 16.2%). An estimated 26.7% experience some form of informal coercion during childbirth. Having a cesarean section or instrumental vaginal birth was associated with an increased risk to experience informal coercion (all risk ratios > 1.5). The risk was also increased for women with a migrant background, women living in more urban regions and women with a risk pregnancy. Also, women to whom having a self-determined vaginal birth is important reported on informal coercion more often. Being at risk for postpartum depression was mostly associated with having an emergency cesarean section, having been transferred to hospital and the experience of informal coercion. Also, women with a migrant background seem to be at a higher risk to develop postpartum depression or having other mental health issues. Finally, women who had a non-instrumental vaginal birth reported higher satisfaction with childbirth experience and women who experienced informal coercion reported lower satisfaction.

Conclusions

One in four women experience informal coercion during childbirth, and this experience is associated with being at risk for postpartum depression and lower satisfaction with childbirth. Health care professionals should make every effort to prevent informal coercion and ensure sensitive aftercare for all new mothers in order to prevent traumatic effects.
Genome-wide analysis of blood lipid metabolites in over 5,000 South Asians reveals biological insights at cardiometabolic disease loci
Authors: Harshfield Eric L. , Fauman Eric B. , Stacey David , Paul Dirk S. , Ziemek Daniel , Ong Rachel M. Y. , Danesh John , Butterworth Adam S. , Rasheed Asif , Sattar Taniya , Zameer-ul-Asar  , Saleem Imran , Hina Zoubia , Ishtiaq Unzila , Qamar Nadeem , Mallick Nadeem Hayat , Yaqub Zia , Saghir Tahir , Hasan Rizvi Syed Nadeem , Memon Anis , Ishaq Mohammad , Rasheed Syed Zahed , Memon Fazal-ur-Rehman , Jalal Anjum , Abbas Shahid , Frossard Philippe , Saleheen Danish , Wood Angela M. , Griffin Julian L. , Koulman Albert
Published: October 2020

Background

Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies.

Methods

We characterised the genetic architecture of the human blood lipidome in 5,662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci.

Results

We identified 359 genetic associations with 255 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 616 genetic associations with 326 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci.

Conclusions

Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.
Vascular Risk Factor Prevalence and Trends in Native Americans With Ischemic Stroke - A National Inpatient Sample Analysis
Authors: Jillella Dinesh V. , Crawford Sara , Lopez Rocio , Zafar Atif , Tang Anne S. , Uchino Ken
Published: October 2020

Introduction

Native Americans have a higher incidence and prevalence of stroke and the highest stroke-related mortality among race-ethnic groups in the United States. We aimed to analyze trends in the prevalence of vascular risk factors among Native Americans with ischemic stroke over the last two decades along with a comparison to the other race-ethnic groups.

Methods

National/Nationwide Inpatient Sample (NIS) database was used to explore the prevalence of risk factors among hospitalized ischemic stroke patients during 2000 - 2016. Ischemic stroke and risk factors of interest were identified using validated ICD-9/10 codes. The race-ethnic groups of interest were Native American, White, Black, Hispanic, Asian/Pacific Islanders, and others. Crude and age-and sex-standardized prevalence estimates were calculated for each risk factor within each race-ethnic group in 6 time periods: 2000-02, 2003-05, 2006-08, 2009-11, 2012-14, and 2015-16. We explored linear trends over the defined time periods using linear regression models, with differences in trends between the Native American group and each of the other race-ethnic groups assessed using interaction terms. The analysis accounted for the complex sampling design, including hospital clusters, NIS stratum, and trend weights for analyzing multiple years of NIS data.

Results

Of the 1,278,784 ischemic stroke patients that were included in the analysis, Native Americans constituted 5472. The age-and-sex-standardized prevalence of hypertension (trend slope = 2.24, p < 0.001), hyperlipidemia (trend slope = 6.29, p < 0.001), diabetes (trend slope = 2.04, p = 0.005), atrial fibrillation/flutter (trend slope = 0.80, p = 0.011), heart failure (trend slope = 0.73, p = 0.036) smoking (trend slope = 3.65, p < 0.001), and alcohol (slope = 0.60, p = 0.019) increased during these time periods among Native Americans, while coronary artery disease prevalence remained unchanged. Similar upward trends of several risk factors were noted across other race-ethnic groups with Native Americans showing larger increases in hypertension prevalence compared to Blacks, Hispanics, and Asian/Pacific Islanders and in smoking prevalence compared to Hispanics and Asian/Pacific Islanders. By the year 2015-2016, Native Americans had the highest overall prevalence of diabetes, coronary artery disease, smoking, and alcohol among all the race-ethnic groups.

Conclusion

The prevalence of most vascular risk factors among ischemic stroke patients has increased in Native Americans and other race-ethnic groups over the last two decades. Significantly larger increases in the prevalence of hypertension and smoking were seen in Native Americans compared to other groups along with them having the highest prevalence in multiple risk factors in recent years.