bluuebunny/crossref_metadata_2025 huggingface dataset:
The Microaggressions Triangle Model: A Humanistic Approach to Navigating Microaggressions in Health Professions Schools
Authors: Ackerman-Barger Kupiri , Jacobs Negar Nicole
Published: September 2020

Microaggressions are types of interactions that create a cognitive load that can impede a health professions student’s ability to perform well in their program. This paper discusses the Microaggressions Triangle Model, which is a framework for understanding microaggressions from a human interaction standpoint. At each point in the model, the authors provide approaches designed to help recipients, sources, and bystanders construct responses that may allow for rebuilding. From a restorative justice standpoint, rebuilding gives all people involved the opportunity to restore their reputations and repair relationships. Rebuilding is about individuals and communities acknowledging and learning from the interaction as a way to promote a climate of inclusion in their organization.
Struggles and Tensions in Antiracism Education in Medical School: Lessons Learned
Authors: Ona Fernando F. , Amutah-Onukagha Ndidiamaka N. , Asemamaw Rina , Schlaff Anthony L.
Published: September 2020

Purpose

Faculty from different racial and ethnic backgrounds developed and piloted an antiracism curriculum initially designed to help medical students work more effectively with patients of color. Learning objectives included developing stronger therapeutic relationships, addressing the effects of structural racism in the lives of patients, and mitigating racism in the medical encounter.

Method

The antiracism curriculum was delivered and evaluated in 2019 through focus groups and written input before and after each module. The process and outcome evaluation used a grounded theory approach.

Results

Three emergent themes reflect how medical students experienced the antiracism curriculum and inform recommendations for integrating an antiracism curriculum into future medical education. The themes are: 1) the differential needs and experiences of persons of color and Whites, 2) the need to address issues of racism within medical education as well as in medical care, and 3) the need for structures of accountability in medical education.

Conclusions

Medical educators must address racism in medical education before seeking to direct students to address it in medical practice.
Histone deacetylase (Rpd3) regulates
Drosophila
early brain development via regulation of Tailless
Authors: Das Paromita , Bhadra Manika Pal
Published: September 2020

Tailless is a committed transcriptional repressor and principal regulator of the brain and eye development in
Drosophila
. Rpd3, the histone deacetylase, is an established repressor that interacts with co-repressors like Sin3a, Prospero, Brakeless and Atrophin. This study aims at deciphering the role of
Rpd3
in embryonic segmentation and larval brain development in
Drosophila
. It delineates the mechanism of Tailless regulation by
Rpd3
, along with its interacting partners. There was a significant reduction in Tailless in
Rpd3
heteroallelic mutant embryos, substantiating that Rpd3 is indispensable for the normal Tailless expression. The expression of the primary readout, Tailless was correlative to the expression of the neural cell adhesion molecule homologue, Fascilin2 (Fas2). Rpd3 also aids in the proper development of the mushroom body. Both Tailless and Fas2 expression are reported to be antagonistic to the epidermal growth factor receptor (EGFR) expression. The decrease in Tailless and Fas2 expression highlights that EGFR is upregulated in the larval mutants, hindering brain development. This study outlines the axis comprising Rpd3, dEGFR, Tailless and Fas2, which interact to fine-tune the early segmentation and larval brain development. Therefore, Rpd3 along with Tailless has immense significance in early embryogenesis and development of the larval brain.
Chemical composition, nutritional profile and
in vivo
antioxidant properties of the cultivated mushroom
Coprinus comatus
Authors: Stilinović Nebojša , Čapo Ivan , Vukmirović Saša , Rašković Aleksandar , Tomas Ana , Popović Mira , Sabo Ana
Published: September 2020

This study investigated the chemical and nutritional profile and antioxidative properties of cultivated
Coprinus comatus
. Proximate analysis revealed that
C. comatus
is rich in carbohydrates, dietary fibres and proteins, and could also be a valuable source of phenolics. Additionally, fat content is low, consisting mainly of polyunsaturated and omega-3 fatty acids. Furthermore, the safety profile of
C. comatus
is satisfactory, with all elements of toxicological importance within the proposed limits. Oral treatment with
C. comatus
for 42 days improved the antioxidant capabilities and ameliorated carbon tetrachloride-induced liver damage in rats, marked by decreased serum aminotransferase levels and lipid peroxidation intensity. Glutathione concentrations increased in a dose-dependent manner. Histological morphometric and immunohistochemical analysis confirmed antioxidative and hepatoprotective potential. These findings imply that cultivated
C.
comatus
could be considered a nutraceutical, having beneficial nutrient and therapeutic properties.
Observing the Mpemba effect with minimal bias and the value of the Mpemba effect to scientific outreach and engagement
Authors: Burridge Henry C. , Hallstadius Oscar
Published: September 2020

The Mpemba effect is the assertion that it is quicker to cool or freeze water when the initial temperature is high. We define the Mpemba effect to have been observed when two samples of water, one initially warmer than the other, are cooled and the initially hotter sample freezes or cools to a prescribed temperature in less time; this assumes that the samples are of the same mass, are at least as pure as drinking water, the cooling is delivered to both samples in the same manner and the same level of insulation is applied to both. Under this definition, we enable repeatable observations of the Mpemba effect by systematically introducing increased nucleation sites (in our case by roughening the container walls with sandpaper) within the cooling environment of the initially warmer sample. We remain able to observe the Mpemba effect when the enthalpy of cooling and freezing the initially warmer sample exceeds that of the initially cooler sample by over 50%, corresponding to a difference in the initial temperatures of around 50 °C. The context of this study, initiated by a high-school student who then carried out all of the experiments, highlights the value of the Mpemba effect as a tool for scientific learning and engagement.
Wald’s martingale and the conditional distributions of absorption time in the Moran process
Authors: Monk Travis , van Schaik André
Published: September 2020

Many models of evolution are stochastic processes, where some quantity of interest fluctuates randomly in time. One classic example is the Moranbirth–death process, where that quantity is the number of mutants in a population. In such processes, we are often interested in their absorption (i.e. fixation) probabilities and the conditional distributions of absorption time. Those conditional time distributions can be very difficult to calculate, even for relatively simple processes like the Moran birth–death model. Instead of considering the time to absorption, we consider a closely related quantity: the number of mutant population size changes before absorption. We use Wald’s martingale to obtain the conditional characteristic functions of that quantity in the Moran process. Our expressions are novel, analytical and exact, and their parameter dependence is explicit. We use our results to approximate the conditional characteristic functions of absorption time. We state the conditions under which that approximation is particularly accurate. Martingales are an elegant framework to solve principal problems of evolutionary stochastic processes. They do not require us to evaluate recursion relations, so when they are applicable, we can quickly and tractably obtain absorption probabilities and times of evolutionary models.
High endemic levels of typhoid fever in rural areas of Ghana may stem from optimal voluntary vaccination behaviour
Authors: Acosta-Alonzo Carmen B. , Erovenko Igor V. , Lancaster Aaleah , Oh Hyunju , Rychtář Jan , Taylor Dewey
Published: September 2020

Typhoid fever has long established itself endemically in rural Ghana despite the availability of cheap and effective vaccines. We used a game-theoretic model to investigate whether the low vaccination coverage in Ghana could be attributed to rational human behaviour. We adopted a version of an epidemiological model of typhoid fever dynamics, which accounted not only for chronic life-long carriers but also for a short-cycle transmission in the immediate environment and a long-cycle transmission via contamination of the water supply. We calibrated the model parameters based on the known incidence data. We found that unless the (perceived) cost of vaccination is negligible, the individually optimal population vaccination rate falls significantly short of the societally optimal population vaccination rate needed to reach herd immunity. We expressed both the herd immunity and the optimal equilibrium vaccination rates in terms of only a few observable parameters such as the incidence rate, demographics, vaccine waning rate and the perceived cost of vaccination relative to the cost of infection. This allowed us not to rely on other uncertain epidemiological model parameters and, in particular, to bypass uncertainties about the role of the carriers in the transmission.
Nucleation properties of isolated shear bands
Authors: Yadav Shwetabh , Sagapuram Dinakar
Published: September 2020

Shear banding, or localization of intense strains along narrow bands, is a plastic instability in solids with important implications for material failure in a wide range of materials and across length scales. In this article, we report on a series of experiments on the nucleation of single isolated shear bands in three model alloys. Nucleation kinetics of isolated bands and characteristic stresses are studied using high-speed
in situ
imaging and parallel force measurements. The results demonstrate the existence of a critical shear stress required for band nucleation. The nucleation stress bears little dependence on the normal stress and is proportional to the shear modulus. These properties are quite akin to those governing the onset of dislocation slip in crystalline solids. A change in the flow mode from shear banding to homogeneous plastic flow occurs at stress levels below the nucleation stress. Phase diagrams delineating the strain, strain rate and temperature domains where these two contrasting flow modes occur are presented. Our work enables interpretation of shear band nucleation as a crystal lattice instability due to (stress-assisted) breakdown of dislocation barriers, with quantitative experimental support in terms of stresses and the activation energy.
Males adjust their manipulation of female remating in response to sperm competition risk
Authors: Moschilla Joe A. , Tomkins Joseph L. , Simmons Leigh W.
Published: September 2020

To reduce the potential for sperm competition, male insects are thought to inhibit the post-mating reproductive behaviour of females through receptivity-inhibiting compounds transferred in the ejaculate. Selection is expected to favour phenotypic plasticity in male post-copulatory expenditure, with males investing strategically in response to their perceived risk of sperm competition. However, the impact that socially cued strategic allocation might have on female post-mating behaviour has rarely been assessed. Here, we varied male perception of sperm competition risk, both prior to and during mating, to determine if a male's competitive environment impacts the extent to which he manipulates female remating behaviour. We found that female Australian field crickets (Teleogryllus oceanicus) mated to males that were reared under sperm competition risk emerged from a shelter in search of male song sooner than did females mated to males reared without risk, but only when mating occurred in a risk-free environment. We also found that females reared in a silent environment where potential mates were scarce emerged from the shelter sooner than females exposed to male calls during development. Collectively, our findings suggest complex interacting effects of male and female sociosexual environments on female post-mating sexual receptivity.
Modeling the combined effect of digital exposure notification and non-pharmaceutical interventions on the COVID-19 epidemic in Washington state
Authors: Abueg Matthew , Hinch Robert , Wu Neo , Liu Luyang , Probert William , Wu Austin , Eastham Paul , Shafi Yusef , Rosencrantz Matt , Dikovsky Michael , Cheng Zhao , Nurtay Anel , Abeler-Dörner Lucie , Bonsall David , McConnell Michael V. , O’Banion Shawn , Fraser Christophe
Published: September 2020

Contact tracing is increasingly being used to combat COVID-19, and digital implementations are now being deployed, many of them based on Apple and Google’s Exposure Notification System. These systems are new and are based on smartphone technology that has not traditionally been used for this purpose, presenting challenges in understanding possible outcomes. In this work, we use individual-based computational models to explore how digital exposure notifications can be used in conjunction with non-pharmaceutical interventions, such as traditional contact tracing and social distancing, to influence COVID-19 disease spread in a population. Specifically, we use a representative model of the household and occupational structure of three counties in the state of Washington together with a proposed digital exposure notifications deployment to quantify impacts under a range of scenarios of adoption, compliance, and mobility. In a model in which 15% of the population participated, we found that digital exposure notification systems could reduce infections and deaths by approximately 8% and 6%, effectively complementing traditional contact tracing. We believe this can serve as guidance to health authorities in Washington state and beyond on how exposure notification systems can complement traditional public health interventions to suppress the spread of COVID-19.
Optimizing direct RT-LAMP to detect transmissible SARS-CoV-2 from primary nasopharyngeal swab and saliva patient samples
Authors: Dudley Dawn M. , Newman Christina M. , Weiler Andrea M. , Ramuta Mitchell D. , Shortreed Cecilia G. , Heffron Anna S. , Accola Molly A. , Rehrauer William M. , Friedrich Thomas C. , O’Connor David H.
Published: September 2020

SARS-CoV-2 testing is crucial to controlling the spread of this virus, yet shortages of nucleic acid extraction supplies and other key reagents have hindered the response to COVID-19 in the US. Several groups have described loop-mediated isothermal amplification (LAMP) assays for SARS-CoV-2, including testing directly from nasopharyngeal swabs and eliminating the need for reagents in short supply. Here we describe a fluorescence-based RT-LAMP test using direct nasopharyngeal swab samples and show consistent detection in clinically confirmed samples, albeit with approximately 100-fold lower sensitivity than qRT-PCR. We demonstrate that adding lysis buffer directly into the RT-LAMP reaction improves the sensitivity of some samples by approximately 10-fold. Overall, the limit of detection (LOD) of RT-LAMP using direct nasopharyngeal swab or saliva samples without RNA extraction is 1×105-1×106 copies/ml. This LOD is sufficient to detect samples from which infectious virus can be cultured. Therefore, samples that test positive in this assay contain levels of virus that are most likely to perpetuate transmission. Furthermore, purified RNA in this assay achieves a similar LOD to qRT-PCR and we provide a revised method to work directly with saliva as starting material. These results indicate that high-throughput RT-LAMP testing could augment qRT-PCR in SARS-CoV-2 screening programs, especially while the availability of qRT-PCR testing and RNA extraction reagents is constrained.
To isolate or not to isolate: The impact of changing behavior on COVID-19 transmission
Authors: Agusto Folashade B. , Erovenko Igor V. , Fulk Alexander , Abu-Saymeh Qays , Romero-Alvarez Daniel , Ponce Joan , Sindi Suzanne , Ortega Omayra , Onge Jarron M. Saint , Peterson A. Townsend
Published: September 2020

The COVID-19 pandemic has caused more than 25 million cases and 800 thousand deaths worldwide to date. Neither vaccines nor therapeutic drugs are currently available for this novel coronavirus. All measures to prevent the spread of COVID-19 are thus based on reducing contact between infected and susceptible individuals. Most of these measures such as quarantine and self-isolation require voluntary compliance by the population. However, humans may act in their (perceived) self-interest only. We construct a mathematical model of COVID-19 transmission with quarantine and hospitalization coupled with a dynamic game model of adaptive human behavior. Susceptible and infected individuals adopt various behavioral strategies based on perceived prevalence and burden of the disease and sensitivity to isolation measures, and they evolve their strategies using a social learning algorithm (imitation dynamics). This results in complex interplay between the epidemiological model, which affects success of different strategies, and the game-theoretic behavioral model, which in turn affects the spread of the disease. We found that the second wave of the pandemic, which has been observed in the US, can be attributed to rational behavior of susceptible individuals, and that multiple waves of the pandemic are possible if the rate of social learning of infected individuals is sufficiently high. To reduce the burden of the disease on the society, it is necessary to incentivize such altruistic behavior by infected individuals as voluntary self-isolation.
FMNL2 interacts with cerebrovascular risk factors to alter Alzheimer’s disease risk
Authors: Raghavan Neha S. , Sariya Sanjeev , Lee Annie J. , Gao Yizhe , Reyes-Dumeyer Dolly , De Jager Philip L. , Bennett David A. , Menon Vilas , Lantigua Rafael A. , Kukull Walter A. , Brickman Adam M. , Manly Jennifer J , Gutierrez Jose , Vardarajan Badri N. , Tosto Giuseppe , Mayeux Richard
Published: September 2020

INTRODUCTION

Late-onset Alzheimer’s disease (AD) frequently co-occurs with cerebrovascular disease. We hypothesized that interactions between genes and cerebrovascular risk factors (CVRFs) contribute to AD risk.

METHODS

Participants age 65 years or older from five multi-ethnic cohorts (N=14,669) were included in genome-wide association meta-analyses for AD including an interaction factor for a CVRF score created from body mass index, hypertension, heart disease, and diabetes. Significant gene level results were substantiated using neuropathological and gene expression data.

RESULTS

At the gene-level, FMNL2 interacted with the CVRF score to significantly modify AD risk (p= 7.7×10-7). A SNP within FRMD4B, rs1498837, was nominally significant (p=7.95×10-7). Increased FMNL2 expression was significantly associated with brain infarcts and AD.

DISCUSSION

FMNL2 is highly expressed in the brain and has been associated with ischemic stroke and failures in endosomal trafficking, a major pathway in AD pathology. The results highlight an interaction between FMNL2 and CVRFs on AD susceptibility.
Assessing the effectiveness of animal therapy on alleviation of anxiety in pre-school children
Authors: Tahan Mohammad , Sadeghifar Azam , Ahangri Elahe
Published: September 2020

Introduction

The purpose of this study was to assess the effectiveness of animal therapy in alleviation of anxiety in pre-school children.

Method

The study was carried out as a quasi-experimental study with pre-test and post-test design and control group. The study population consisted of 33 anxious 5-7years old children (participated in a welfare anxiety screening plan held by Counseling Center, Tehran-Iran) between 2018 and 2019. The participants took part in the study voluntarily.

The subjects were randomly divided into experimental and control groups (10 in each group). The experimental group was exposed to 8 sessions of animal therapy. The research instrument was Spence Preschool Anxiety Scale (Parent Form) and the data were analyzed on SPSS 21 software.

Results

The results showed that animal therapy had a significant effect on general anxiety score after adjusting for post-test scores (f= 32.49 and p= 0.001) with the effect equal to 0.70. In addition, the effect of animal therapy on anxiety of separation (f= 5.63, p= 0.03), generalized anxiety disorder (f= 8.56, p= 0.01), social phobia (f= 14.58, p= 0.002) and specific anxiety (f= 11.63, p= 0.005) was significant with effects equal to 0.30, 0.40, 0.53, and 0.47, respectively. The results also showed that the effect of animal therapy on obsession was not significant (p>0.05).

Conclusion

Therefore, it can be concluded that Animal therapy is effective in alleviating anxiety in children.
Olfactory impairment is related to tau pathology and neuroinflammation in Alzheimer’s disease
Authors: Klein Julia , Yan Xinyu , Johnson Aubrey , Tomljanovic Zeljko , Zou James , Polly Krista , Honig Lawrence S. , Brickman Adam M. , Stern Yaakov , Devanand D.P. , Lee Seonjoo , Kreisl William C.
Published: September 2020

Background

Olfactory impairment is evident in Alzheimer’s disease (AD), however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood.

Objective

To determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation.

Methods

Participants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent 18F-MK-6240 PET and fifty-three underwent 11C-PBR28 PET to measure tau pathology and neuroinflammation, respectively. Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau) and β-amyloid (Aβ42).

Results

Low UPSIT performance was associated with greater18F-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex and posterior cingulate cortex (p < 0.05). Similar relationships were seen for 11C-PBR28. These relationships were primarily driven by amyloid-positive participants. Lower UPSIT performance was associated with greater CSF concentrations of t-tau and p-tau (p < 0.05). Amyloid status and cognitive status exhibited independent effects on UPSIT performance (p < 0.01).

Conclusions

Olfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. The independent association of amyloid-positivity and cognitive impairment with odor identification suggests that low UPSIT performance may be a marker for AD pathophysiology in cognitive normal individuals, although impaired odor identification is associated with both AD and non-AD related neurodegeneration.

NCT Registration Numbers:NCT03373604; NCT02831283
First “snap-shot” meta-analysis to estimate the prevalence of serum antibodies to SARS-CoV-2 in humans
Authors: Rostami Ali , Sepidarkish Mahdi , Leeflang Mariska , Riahi Seyed Mohammad , Shiadeh Malihe Nourollahpour , Esfandyari Sahar , Mokdad Ali H , Hotez Peter J. , Gasser Robin B.
Published: September 2020

Background

COVID-19 is arguably the number-one public health concern worldwide, and efforts are now escalating to control its spread.

Objective

In this study, we undertake a meta-analysis to estimate the global and regional anti-SARS-CoV-2 seroprevalence rates in humans and assess whether seroprevalence associates with geographical, climatic and socio-demographic factors.

Data sources

We systematically reviewed PubMed, Scopus, Embase, medRxiv and bioRxiv for peer-reviewed articles or preprints (up to 14 August 2020).

Study eligibility criteria

Population-based studies describing prevalence of anti-SARS-CoV-2 serum antibodies in general people.

Participants

general people who were tested for prevalence of anti-SARS-CoV-2 serum antibodies.

Interventions

There were no interventions.

Methods

We used random-effects model to estimate pooled seroprevalence, and then extrapolated these findings to the global population (for 2020). Sub-group and meta-regression analyses explored potential sources of heterogeneity in the data and relationships between seroprevalence and socio-demographic, geographical and climatic factors.

Results

In total, 47 serological studies involving 399,265 people from 23 countries met the inclusion criteria. The pooled seroprevalence of SARS-CoV-2 in general people was estimated at 3.38% (95% CI, 3.05%–3.72%; 15,879/399,265). On a regional basis, we determined seroprevalence estimates of 5.27% (3.97–6.57%) in Northern Europe; 4.41% (2.20–6.61%) in Southern Europe; 4.41% (3.03– 5.79%) in North America; 3.17% (1.96–4.38%) in Western Europe; 2.02% (1.56–2.49%) in the Eastern Asia; and 1.45% (0.95–1.94%) in South America. Extrapolating to the 2020 world population, we estimated that 263,565,606 individuals had been exposed or infected with SARS-CoV-2 at the first wave of the pandemic. A significantly higher seroprevalence was related to higher income levels and human development indices, higher geographical latitudes and lower mean environmental temperatures.

Interpretation

This study reinforces that SARS-CoV-2 infection is a very rapidly-spreading communicable disease and calls for routine surveys to constantly monitor temporal changes in seroprevalence around the globe.
Outcome of SARS-CoV-2 infection linked to MAIT cell activation and cytotoxicity: evidence for an IL-18 dependent mechanism
Authors: Flament H. , Rouland M. , Beaudoin L. , Toubal A. , Bertrand L. , Lebourgeois S. , Gouda Z. , Rousseau C. , Soulard P. , Hurtado-Nedelec M. , Luce S. , Bailly K. , Andrieu M. , Boitard C. , Vallet-Pichard A. , Gautier JF. , Ajzenberg N. , Terrier B. , Pene F. , Ghosn J. , Yazdanpanah Y. , Visseaux B. , Descamps D. , Timsit JF. , Monteiro R.C. , Lehuen A.
Published: September 2020

Immune system dysfunction is paramount in Coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in a cohort of 182 patients including patients at various stages of disease activity. A profound decrease of MAIT cell counts in blood of critically ill patients was observed. These cells showed a strongly activated and cytotoxic phenotype that positively correlated with circulating pro-inflammatory cytokines, notably IL-18. MAIT cell alterations markedly correlated with disease severity and patient mortality. SARS-CoV-2-infected macrophages activated MAIT cells in a cytokine-dependent manner involving an IFNα-dependent early phase and an IL-18-induced later phase. Therefore, altered MAIT cell phenotypes represent valuable biomarkers of disease severity and their therapeutic manipulation might prevent the inflammatory phase involved in COVID-19 aggravation.
Could Deficiencies in South African Data Be the Explanation for Its Early SARS-CoV-2 Peak?
Authors: Childs S. J.
Published: September 2020

The SARS-CoV-2 pandemic peaked very early in comparison to the thresholds predicted by an analysis of prior lockdown regimes. The most convenient explanation is that some, external factor changed the value of the basic reproduction number, r0; and there certainly are arguments for this. Other factors could, nonetheless, have played a role. This research attempts to reconcile the observed peak with the thresholds predicted by lockdown regimes similar to the one in force at the time. It contemplates the effect of two, different, hypothetical errors in the data: The first is that the true level of infection has been underestimated by a multiplicative factor, while the second is that of an imperceptible, pre-existing, immune fraction of the population. While it is shown that it certainly is possible to manufacture the perception of an early peak as extreme as the one observed, solely by way of these two phenomena, the values need to be fairly high. The phenomena would not, by any measure, be insignificant. It also remains an inescapable fact that the early peak in infections coincided with a fairly profound change in r0; in all the contemplated scenarios of data-deficiency.
Adenoma detection rate in fecal immunochemical test positive colonoscopies: a population-based observational study
Authors: Denis Bernard , Gendre Isabelle , Tuzin Nicolas , Guignard Anne , Perrin Philippe , Rahmi Gabriel
Published: September 2020

Background and aims

Neoplasia-related indicators, such as adenoma detection rate (ADR), are a priority in the quality improvement process for colonoscopy. Our aim was to assess and compare different detection and characterization indicators in fecal occult blood test (FOBT)-positive colonoscopies, to analyze the factors influencing their variance, and to propose benchmarks.

Methods

Retrospective analysis of prospectively collected data from all colonoscopies performed between 2007 and 2019 after a positive guaiac-based FOBT or a fecal immunochemical test (FIT) in the population-based colorectal cancer (CRC) screening program conducted in Alsace, part of the French national program. Detection indicators included ADR, NewADR (including proximal serrated lesions), mean number of adenomas per colonoscopy, and proximal serrated lesion detection rate. Characterization indicators included non-neoplastic polyp detection rate.

Results

Overall, 13.455 FIT-positive colonoscopies were performed by 116 endoscopists. The overall ADR was 57.6% (95%CI 56.8-58.5). For each 10 μg/g increase in fecal hemoglobin concentration, a 2% increase in ADR was observed. Endoscopists whose ADR was ≥55% were high detectors for all neoplasia, including proximal serrated lesions and number of adenomas. The non-neoplastic polyp detection rate was 39.5% in highest detectors (ADR >70%), significantly higher than in lower detectors (21.4%) (p<0.001). There was a strong correlation between detection and characterization indicators, e.g. between proximal serrated lesion and non-neoplastic polyp detection rates (Pearson = 0.73; p<0.01).

Conclusions

A single indicator, NewADR, including proximal serrated lesions, is enough to assess the neoplasia yield of colonoscopy provided the target standard is raised between 55% and 70% in FIT-positive colonoscopies (65-80% in men, 45-60% in women).
Early Prediction of Sepsis in the ICU using Machine Learning: A Systematic Review
Authors: Moor Michael , Rieck Bastian , Horn Max , Jutzeler Catherine R. , Borgwardt Karsten
Published: September 2020

Abstract

Background

Sepsis is among the leading causes of death in intensive care units (ICU) world-wide and its recognition, particularly in the early stages of the disease, remains a medical challenge. The advent of an affluence of available digital health data has created a setting in which machine learning can be used for digital biomarker discovery, with the ultimate goal to advance the early recognition of sepsis.

Objective

To systematically review and evaluate studies employing machine learning for the prediction of sepsis in the ICU.

Data sources

Using Embase, Google Scholar, PubMed/Medline, Scopus, and Web of Science, we systematically searched the existing literature for machine learning-driven sepsis onset prediction for patients in the ICU.

Study eligibility criteria

All peer-reviewed articles using machine learning for the prediction of sepsis onset in adult ICU patients were included. Studies focusing on patient populations outside the ICU were excluded.

Study appraisal and synthesis methods

A systematic review was performed according to the PRISMA guidelines. Moreover, a quality assessment of all eligible studies was performed.

Results

Out of 974 identified articles, 22 and 21 met the criteria to be included in the systematic review and quality assessment, respectively. A multitude of machine learning algorithms were applied to refine the early prediction of sepsis. The quality of the studies ranged from “poor” (satisfying ≤ 40% of the quality criteria) to “very good” (satisfying ≥ 90% of the quality criteria). The majority of the studies (n= 19, 86.4%) employed an offline training scenario combined with a horizon evaluation, while two studies implemented an online scenario (n= 2, 9.1%). The massive inter-study heterogeneity in terms of model development, sepsis definition, prediction time windows, and outcomes precluded a meta-analysis. Last, only 2 studies provided publicly-accessible source code and data sources fostering reproducibility.

Limitations

Articles were only eligible for inclusion when employing machine learning algorithms for the prediction of sepsis onset in the ICU. This restriction led to the exclusion of studies focusing on the prediction of septic shock, sepsis-related mortality, and patient populations outside the ICU.

Conclusions and key findings

A growing number of studies employs machine learning to optimise the early prediction of sepsis through digital biomarker discovery. This review, however, highlights several shortcomings of the current approaches, including low comparability and reproducibility. Finally, we gather recommendations how these challenges can be addressed before deploying these models in prospective analyses.

Systematic review registration number

CRD42020200133
Hydroxicloroquine for Pre-Exposure Prophylaxis for SARS-COV-2
Authors: de la Iglesia Jaime López , Fernández Naiara Cubelos , Flores Roi Naveiro , Gómez Marina Montoro , González de Haro Francisco Javier , González María Ajenjo , Vicente Estefanía Tobal , Gil de Gómez María Lamuedra , Guisado María Teresa Nuevo , Gómez Isabel Torio , Andrada Ana Peñalver , Cao Nuria Martínez , Figaredo Paula González , García Carlos Robles , Machón Lidia Anastasia Alvarado , Alcalde Ángeles Lafont , Rilo José Cesáreo Naveiro
Published: September 2020

SARS-CoV-2 infection has a high transmission level. At the present time there is not a specific treatment approved but it is known that, in vitro, chloroquine and hydroxychloroquine can inhibit the coronavirus.

Objective

verifying if patients with autoimmune diseases that are on treatment with HCQ have less incidence and severity on COVID-19.

Material and methods

this is a retrospective cohort study. The exposed cohort was formed by individuals with autoimmune diseases with HCQ treatment. The control cohort was randomly selected using the Health Card database. To deal with confounding variables and evaluate the effect of HCQ on the incidence and severity of SARS-CoV-2 infection, propensity score matching was used. Risk difference and paired percentage difference between exposed and non-exposed groups was estimated.

Results

919 individuals formed the exposed cohort and 1351 the control cohort. After matching, there were 690 patients on each group. During the time of the study, in the exposed group there were 42 (6.1%) individuals with suspected COVID-19, 12(1.7%) with confirmed COVID-19 and 3(0.4%) were hospitalized. In the control group there were 30(4.3%) individuals with suspected COVID-19, 13(1.9%) with confirmed COVID-19 and 2(0.3%) were hospitalized. The risk difference between each cohort was: 0.017(−0.05-0.04) for suspected COVID-19; -0.014(−0.015-0.012) for confirmed COVID-19 and 0.001(−0.007-0.007) for hospitalized patients. There were not significant differences.

Conclusion

there is no difference neither on the incidence nor on the severity of COVID-19 between patients with autoimmune diseases with HCQ treatment and patients that do not take HCQ.
Evaluating the design and implementation of an adapted Plan-Do-Study-Act (PDSA) approach to improve health system bottlenecks in Nigeria
Authors: Eboreime Ejemai Amaize , Olawepo John Olajide , Banke-Thomas Aduragbemi , Ramaswamy Rohit
Published: September 2020

Background

The Plan-Do-Study-Act (PDSA) cycle is fundamental to many quality improvement (QI) models. For the approach to be effective in the real-world, variants must align with standard elements of the PDSA at the design stage. The adapted design must also be implemented with fidelity. Gaps at the adaptation or implementation stages result in design and implementation failures respectively. Using Taylor’s framework, this study evaluates the alignment between theory, design and implementation of the DIVA (Diagnose-Intervene-Verify-Adjust) model, a PDSA variant adapted for Nigeria’s health system performance improvement.

Methods

An iterative consensus building approach was used to develop a scorecard evaluating new conceptual indices of design and implementation of QI interventions (design and implementation index, defects and gaps). The scorecard assigned quantitative scores that measured the extent to which the reported or documented design or implementation activity aligned with Taylor’s theoretical framework.

Results

Design (adaptation) scores were across all standard features indicating that design was well adapted to the typical PDSA. Conversely, implementation fidelity scores were only optimal with two standard features: prediction-based test of change and the use of data over time. The other features, use of multiple iterative cycles and documentation, had implementation gaps of 17% and 50% respectively. This may imply that observed effectiveness deficits of DIVA may be attributable to implementation rather than design gaps.

Conclusions

The effectiveness of QI interventions depend of good contextual adaptation and implementation fidelity such that core features (theory and internal logic) must not be compromised. This study demonstrates how both adaptation and implementation are important for success of QI interventions. It also presents an approach for evaluating other QI models using Taylor’s PDSA assessment framework as a guide, which might serve to strengthen the theory behind future QI models, and provide guidance on their appropriate use.
Health and Economic Effects of COVID-19 control in Australia: Modelling and quantifying the payoffs of ‘hard’ versus ‘soft’ lockdown
Authors: Grafton R. Quentin , Parslow John , Kompas Tom , Glass Kathryn , Banks Emily , Lokuge Kamalini
Published: September 2020

Objective(s)

Australia requires high quality evidence to optimise likely health and economy outcomes to effectively manage the current resurgence of COVID-19. We hypothesise that the most stringent social distancing (SD) measures (100% of level in Australia in April 2020) deliver better public health and economy outcomes.

Design

‘Fit-for-purpose’ (individual-based and compartment) models were used to simulate the effects of different SD and detection strategies on Australian COVID-19 infections and the economy from March to July 2020. Public reported COVID-19 data were used to estimate model parameters.

Main outcome measures

Public health and economy outcomes for multiple social distancing levels were evaluated, assessing “hard” versus “soft” lockdowns, and for early versus later relaxation of social distancing. Outcomes included costs and the timing and magnitude of observed COVID-19 cases and cumulative deaths in Australia from March to June 2020.

Results

Higher levels of social distancing achieve zero community transmission with 100% probability and lower economy cost while low levels of social distancing result in uncontrolled outbreaks and higher economy costs. High social distancing total economy costs were $17.4B versus $41.2B for 0.7 social distancing. Early relaxation of suppression results in worse public health outcomes and higher economy costs.

Conclusion(s)

Better public health outcomes (reduced COVID-19 fatalities) arepositivelyassociated with lower economy costs and higher levels of social distancing; achieving zero community transmissionlowersboth public health and economy costs compared to allowing community transmission to continue; and early relaxation of social distancingincreasesboth public health and economy costs.

Significance

The knownis that COVID-19 infections can be suppressed with social distancing (SD) measures of sufficient stringency and duration.

The newis we find highest levels of SD (100% SD that prevailed in April 2020) generate much lower COVID-9 deaths; reduced SD days; increased economic activity; and much higher probability of elimination over a subsequent 12-month period than lower levels of SD.

The implicationsare that greater levels of SD are preferred to lower SD because they deliver both better public health and lower economy costs.
Rapid Retreat of the Pacific Maritime Forest
Authors: Kral George , Putnam Melodie , Rupp David
Published: September 2020

The temperate maritime climate of the Pacific Northwest region of the United States supports the world’s tallest and most economically productive conifer forests. These forests are vital to local ecosystems and society, and climate perturbations are likely to adversely affect the services these forests provide. This study presents a simple, easily replicated methodology for assessing effects of climate change in these local forests, using species with differential climatic ranges as ecological barometers. A comparative analysis of warm-adapted and cool-adapted species co-occurring within a warming but otherwise climatically homogenous area near the southeast margin of the Pacific maritime forest reveals dramatic differences in tree health and mortality between these climatically differentiated species groups. Our results strongly suggest a rapid decline at the southeastern extent of the Pacific maritime temperate forest, and a need to immediately modify local land management practices to address this new reality.
Prolactin and DNA damage trigger an anti-breast cancer cell immune response
Authors: Atici Ödül Karayazi , Govindrajan Nayantara , Gonzalez Isbel Lopetegui , Finney Constance A. M. , Shemanko Carrie S.
Published: September 2020

There are conflicting reports on the role of prolactin (PRL) in breast cancer, and its role within the context of the tumour microenvironment is not well understood. In our previous study, we demonstrated a cross-talk between the ataxia telangiectasia-mutated (ATM) DNA damage response pathway and the PRL-Janus-kinase-2 (JAK2)-signal transducer and activator of transcription-5 (STAT5)-heat shock protein-90 (HSP90) pathway. To investigate the role of PRL in tumour initiation and the effect of DNA damage in vivo, we used a model of breast cancer initiation that assesses the ability of breast cancer cells to initiate orthotopic xenograft tumour formation after DNA damage. Breast cancer cells engineered to secrete human PRL or the control cells, were treated with the DNA damaging agent doxorubicin or vehicle and injected into the mammary fat pad of immune-deficient SCID mice. PRL secretion from human breast cancer cells did not change the tumour latency compared to controls, although combined doxorubicin and PRL treatment increased tumour latency. Depletion of glycolipid asialo ganglioside-GM1 positive immune cells using anti-asialo GM1 antibody resulted in faster tumour formation only in the PRL-secreting breast cancer cells that were pre-treated with doxorubicin, and not in the PRL-only or empty vector controls. Additionally, doxorubicin plus PRL treatment of breast cancer cells were shownin vitroto attract cytotoxic NK cells compared to controls, and that this was dependent on the PRLR. These results may shed light on the conflicting reports of PRL in breast cancer and demonstrate that combined breast cancer cell DNA damage and PRL exposure results in anti-tumour activity of asialo-GM1-positive immune cells.
Deficient spermiogenesis in mice lackingRlim
Authors: Wang Feng , Gervasi Maria G. , Bošković Ana , Sun Fengyun , Rinaldi Vera D. , Yu Jun , Wallingford Mary C. , Tourzani Darya A. , Mager Jesse , Zhu Lihua J. , Rando Oliver J. , Visconti Pablo E. , Strittmatter Lara , Bach Ingolf
Published: September 2020

The X-linked geneRlimplays major roles in female mouse development and reproduction, where it is crucial for the maintenance of imprinted X chromosome inactivation in extraembryonic tissues of embryos. However, while females carrying a systemicRlimknockout (KO) die around implantation, maleRlimKO mice appear healthy and are fertile, raising questions as to the pressures drivingRlimgene selection during evolution. Here we report an important role forRlimin testis where it is highly expressed in post-meiotic round spermatids as well as in Sertoli cells. Systemic deletion of theRlimgene leads to lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility andin vitrofertilization rates. Targeting the conditionalRlimcKO specifically to the spermatogenic cell lineage largely recapitulates this phenotype. These results reveal functions ofRlimin male reproduction specifically in round spermatids during spermiogenesis with likely evolutionary implications.
F-box protein At1g08710 negatively regulates root length and imparts drought stress tolerance inArabidopsis thaliana
Authors: Rao Venkateswara , Vijaybhaskar Virupapuram
Published: September 2020

Plants experience abiotic stresses throughout their life cycle and accordingly respond to tide over the unfavorable conditions. Drought or water deficit is one such condition to which plants respond in various ways including the ubiquitin proteasome system (UPS). Ubiquitin E3 ligases are a diverse family of protein complexes of which Skp1□Cullin□F□box (SCF) class mediate the ubiquitination and subsequent proteolytic turnover of proteins. F□box protein subunit plays crucial role in imparting specificity for selective degradation of target proteins. Here we report the function ofArabidopsisF-box proteinAt1g08710in drought stress adaptation. As F-box protein is a constituent of SCF complex, here it is shown interacting with ASK1 and Cullin1. F-box protein localizes to both nucleus and membrane. F-box gene transcript accumulates highly in root and is altered in response to drought stress conditions. F-box protein interacts with a transcriptional co-activator protein ADA2b. F-box mutant plants displayed better growth under drought stress conditions compared to the wild type with a reduced accumulation of H2O2and malondialdehyde (MDA). Drought responsive genesRD29A, RD22, ABI3expression is also induced in F-box mutant plants. These results indicate F-box protein At1g08710 plays a role in drought stress adaptation inArabidopsis thaliana.

Highlights

F-box geneAt1g08710encodes a nuclear, membrane localized protein.

F-box protein At1g08710 interacts with transcriptional co-activator protein ADA2b.

F-box protein imparts drought stress tolerance by modulating H2O2and MDA content.

Drought response genesRD29A, RD22, ABI3expression is induced in F-box mutant plants.