bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical Image Retrieval Using Convolution Neural Networks
Authors: Kalaivani N , Devi D , Sophia Dr. S , Manimaran N , Kowsalya P
Published: December 2020

In this paper, medical image retrieval is done in an effective manner by using convolution neural network (CNN). This proposed system locates reference tags and classes the DICOM images using image processing techniques and retrieval of images are done by using GUI panel. First, the deep learning technique is used to extract powerful features of the image for tag description. Conversely, this technique performs tag matching directly by passing suitable parameters which recognizes the classes as queries. The comparison features are able to capture the general form of the input image and its class based on image tags. Here, we have used a collection of 22 classes of database to demonstrate the efficiency of our system. The experimental results show the classification of images by deep learning algorithm which is used to gain the rate of retrieval accuracy by using MATLAB.
Real Time Emotion Analysis Usingbrainwavesin Comparison to Facial Expression
Authors: Devi S. , Rajalakshmi Dr. M. , Saranya S. , Jeevanandan B. , Ramya A.
Published: December 2020

Emotions play a vital role in human living and are correlated with every single word which is being spoken, without them life will be saturated and irrelevant. Understanding of the real apparent facial expressions might be difficult because part of the emotion might not be revealed outside by everyone. In the proposed method, the emotions of the human are analyzed in two different ways so that the real hidden emotion of the subject can be detected. Every human has unique brain waves, which gives better accuracy than other techniques. It ensures that the facial expression exhibited outside is real or not. The emotion analyzed will be useful in treating the person with high mental stress and also infinding the emotion of differently abled person who requires medical treatment.
Cognitive Aspect of Designing Ethnicity
Authors: Vorontsova Valeriya Leonidovna , Salimgareev Maxim Vladimirovich , Salimgareev Dmitry Vladimirovich
Published: December 2020

The problem of cognitive construction of consolidating mechanisms by analyzing the phenomenon of common sense as the cognitive basis of solidarity, leading to a stable integrity of ethnic structures, is considered. The work uses a system analysis, in which the content of intelligence and ethnic structures are understood as integral systems capable of deep integration. It was found that the presence of ethnicity at the borders of social and biological transforms it into a phenomenon with a high degree of transformation, and especially in the imaginary space of identity. A cognitive mechanism for constructing identification, which ultimately generates certain models of ethnic behavior, seems to be a systemic element that allows any ethnic images to function. Common sense is one of the methods of constructing ethnic, goal-oriented activity. It can potentially act not only as a source of everyday communication, but also initiate both internal and external cooperative activities of ethnic entities united by an understanding of the common social good, including the good of the planetary. The authors make an attempt to comprehend the cognitive conditions for the functioning of ethnicity through the prism of the concept of common sense - the universal anthropological basis of a conscious social good. Common sense defines historical memory, operational reactions in the moment of the present, and a joint vision of the future. This important ability is based on a common basis for any ethnic group - the biopsychosocial nature of the cognitive capabilities of most members of the group. It is in this process of collective self-awareness that social intuition manifests itself, that is, such an integral socio-psychological characteristic of the subject of social action, which includes the ability to effectively predict the development of social situations.
Reversible fuel electrode supported solid oxide cells fabricated by aqueous multilayered tape casting
Authors: Bernadet L , Morales M , Capdevila X G , Ramos F , Monterde M C , Calero J A , Morata A , Torrell M , Tarancón A
Published: December 2020

Fuel electrode supported solid oxide cells (SOCs) have been developed on an industrial scale using the aqueous tape-casting technique. The NiO–yttria-stabilized zirconia Y2O3–ZrO2 (YSZ) fuel electrode and YSZ electrolyte have been manufactured by multilayer co-laminated tape casting. Details of the tape-casting slurry formulations are described and discussed. Two types of cells were fabricated with different microstructures of the NiO–YSZ support discussed. Good electrochemical performance and stability in SOFC mode at 750 °C and 0.7 V for both button cells reaching around >0.75 W cm−2 and with no measurable degradation after >700 h were observed. The selected cell was scaled up to large-area cells (36 cm2 of the active area) and electrochemically tested at 750 °C in a single repetition unit (SRU) in SOFC (Solid Oxide Fuel Cell), SOEC (Solid Oxide Electrolysis Cell) and co-SOEC (Solid Oxide co-Electrolysis Cell) mode, and in a short-stack of two SRUs in SOFC mode. A current up to 17 A was obtained at 1.4 V (0.7 V cell−1) with the short-stack configuration in SOFC mode, corresponding to ∼0.5 A cm−2 and 24 W. The performances of the aqueous-based SOC cells can be considered highly remarkable, thus supporting the success in scaling the fabrication of SOC stacks using more environmentally friendly processes than conventional ones.
Colossal grain growth in Cd(Se,Te) thin films and their subsequent use in CdTe epitaxy by close-spaced sublimation
Authors: Albin David S , Amarasinghe Mahisha , Reese Matthew O , Moseley John , Moutinho Helio , Metzger Wyatt K
Published: December 2020

Many technologies deposit thin films on inexpensive substrates, resulting in small grains due to classic nucleation and grain growth theory. For example, state-of-the-art solar cells are made by depositing CdSeTe and CdTe layers on inexpensive glass coated with nanocrystalline transparent conducting oxides (TCOs), like SnO2. Characteristically, the grain size of these films is on the order of the film thickness, i.e. a few microns. CdTe small-grain films have poor electro-optical properties and require CdCl2 passivation which fails to fully passivate grain boundaries, causes carrier compensation, and prevents implementing other II–VI alloys and materials to improve performance. Here, we present a method to increase grain size to 1 mm in CdSexTe1−x thin films deposited on glass/TCO substrates without CdCl2 treatment. The colossal grain growth is driven by mechanisms distinct from classic nucleation, grain growth, and Ostwald ripening and only occurs at low selenium content (x ∼ 0.1). We also demonstrate how these films can serve as templates for subsequent large-grain epitaxy of other compositions like CdTe, again without exposure to CdCl2. The results open new paths for thin film solar cell technology, and thin film devices in general.
A unifying framework for rare variant association testing in family-based designs, including higher criticism approaches, SKATs, and burden tests
Authors: Hecker Julian , Townes F William , Kachroo Priyadarshini , Laurie Cecelia , Lasky-Su Jessica , Ziniti John , Cho Michael H , Weiss Scott T , Laird Nan M , Lange Christoph
Published: December 2020

Motivation

Analysis of rare variants in family-based studies remains a challenge. Transmission-based approaches provide robustness against population stratification, but the evaluation of the significance of test statistics based on asymptotic theory can be imprecise. Also, power will depend heavily on the choice of the test statistic and on the underlying genetic architecture of the locus, which will be generally unknown.

Results

In our proposed framework, we utilize the FBAT haplotype algorithm to obtain the conditional offspring genotype distribution under the null hypothesis given the sufficient statistic. Based on this conditional offspring genotype distribution, the significance of virtually any association test statistic can be evaluated based on simulations or exact computations, without the need for asymptotic approximations. Besides standard linear burden-type statistics, this enables our approach to also evaluate other test statistics such as variance components statistics, higher criticism approaches, and maximum-single-variant-statistics, where asymptotic theory might be involved or does not provide accurate approximations for rare variant data. Based on these P-values, combined test statistics such as the aggregated Cauchy association test (ACAT) can also be utilized. In simulation studies, we show that our framework outperforms existing approaches for family-based studies in several scenarios. We also applied our methodology to a TOPMed whole-genome sequencing dataset with 897 asthmatic trios from Costa Rica.

Availability and implementation

FBAT software is available at https://sites.google.com/view/fbatwebpage. Simulation code is available at https://github.com/julianhecker/FBAT_rare_variant_test_simulations. Whole-genome sequencing data for ‘NHLBI TOPMed: The Genetic Epidemiology of Asthma in Costa Rica’ is available at https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000988.v4.p1.

Supplementary information

Supplementary data are available at Bioinformatics online.
Can aspirin use reduce the risk of pancreatic cancer: an updated systematic review and meta-analysis
Authors: Wu Dong , Zhou Bin , Yang Jian , Qiu Fa-bo , Hu San-yuan , Zhan Han-xiang
Published: December 2020

Background:

Chemoprevention effect of aspirin for pancreatic cancer (PC) remains unclear. Here we performed an updated systematic review and meta-analysis to investigate the real association between aspirin consumption and risk of PC.

Methods:

PubMed, Web of Science, EMBASE and the Cochrane Database were systematic searched to identify the potential studies. Odds ratio (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of associations.

Results:

Thirteen studies and approximately 28,440 participants were included. Aspirin significantly reduced the incidence of PC (OR, 0.82; 95% CI, 0.73–0.93) in case-control studies. However, the overall results did not reveal an obvious association (OR, 0.92; 95% CI, 0.74–1.16). Both low-dose (OR = 0.86) and high-dose (OR = 0.80) aspirin intake showed prevention effect. In addition, low frequency (OR, 0.87; 95% CI, 0.73–1.05) and high frequency (OR, 0.84; 95% CI, 0.69–1.03) seemed to be equally associated with decreased risk for PC. Aspirin consumption longer than 10 years use seems to have better effect (OR, 0.73; 95% CI, 0.51–1.04) than shorter aspirin use (OR, 0.94; 95% CI, 0.77–1.15).

Conclusions:

Our study indicated that aspirin use might be associated with decreased risk of PC, especially at high doses. But we still need to be cautious when interpreting the results.
Word and Nonword Reading Efficiency in Postlingually Deafened Adult Cochlear Implant Users
Authors: Tamati Terrin N. , Vasil Kara J. , Kronenberger William G. , Pisoni David B. , Moberly Aaron C. , Ray Christin
Published: December 2020

Hypothesis:

This study tested the hypotheses that 1) experienced adult cochlear implants (CI) users demonstrate poorer reading efficiency relative to normal-hearing controls, 2) reading efficiency reflects basic, underlying neurocognitive skills, and 3) reading efficiency relates to speech recognition outcomes in CI users.

Background:

Weak phonological processing skills have been associated with poor speech recognition outcomes in postlingually deaf adult CI users. Phonological processing can be captured in nonauditory measures of reading efficiency, which may have wide use in patients with hearing loss. This study examined reading efficiency in adults CI users, and its relation to speech recognition outcomes.

Methods:

Forty-eight experienced, postlingually deaf adult CI users (ECIs) and 43 older age-matched peers with age-normal hearing (ONHs) completed the Test of Word Reading Efficiency (TOWRE-2), which measures word and nonword reading efficiency. Participants also completed a battery of nonauditory neurocognitive measures and auditory sentence recognition tasks.

Results:

ECIs and ONHs did not differ in word (ECIs: M = 78.2, SD = 11.4; ONHs: M = 83.3, SD = 10.2) or nonword reading efficiency (ECIs: M = 42.0, SD = 11.2; ONHs: M = 43.7, SD = 10.3). For ECIs, both scores were related to untimed word reading with moderate to strong effect sizes (r = 0.43–0.69), but demonstrated differing relations with other nonauditory neurocognitive measures with weak to moderate effect sizes (word: r = 0.11–0.44; nonword: r = (−)0.15 to (−)0.42). Word reading efficiency was moderately related to sentence recognition outcomes in ECIs (r = 0.36–0.40).

Conclusion:

Findings suggest that postlingually deaf adult CI users demonstrate neither impaired word nor nonword reading efficiency, and these measures reflect different underlying mechanisms involved in language processing. The relation between sentence recognition and word reading efficiency, a measure of lexical access speed, suggests that this measure may be useful for explaining outcome variability in adult CI users.
Cochlear Implantation and Electric Acoustic Stimulation in Children With TMPRSS3 Genetic Mutation
Authors: Holder Jourdan T. , Morrel William , Rivas Alejandro , Labadie Robert F. , Gifford René H.
Published: December 2020

Background:

Mutations in the TMPRSS3 gene, although rare, can cause high frequency hearing loss with residual hearing at low frequencies. Several previous studies have reported cochlear implant (CI) outcomes for adults with TMPRSS3 mutation with mixed results. Although some studies have suggested that TMPRSS3 is expressed in spiral ganglion cells, it remains unclear if previously reported poor CI outcomes in this population were secondary to long durations of deafness or to the effects of the TMPRSS3 mutation. To date, no studies in the literature have reported CI outcomes for children with TMPRSS3 mutation treated with CI.

Objective:

The current case series aimed to describe outcomes for three children with sloping hearing loss caused by TMPRSS3 mutation who underwent bilateral CI.

Study Design:

Case series.

Setting:

Academic medical center.

Patients:

Three children (3–4 yr) with TMPRSS3 mutation and normal sloping to profound high frequency hearing loss.

Interventions:

CI and electric acoustic stimulation (EAS).

Main Outcome Measures:

Outcome measures were residual hearing thresholds, speech recognition scores, and electrode placement determined via intraoperative CT imaging.

Results:

All three children maintained residual acoustic hearing and received benefit from EAS. Mean change in low-frequency pure-tone average was 17 dB. Mean postoperative word and sentence recognition scores in the bilateral EAS condition were 80 and 75%, respectively.

Conclusions:

Results indicate that CI with EAS is an appropriate treatment for children with TMPRSS3 genetic mutation. Pediatric results from this case series show more favorable CI outcomes than are currently reported for adults with TMPRSS3 mutation suggesting that the intervention may be time sensitive.
Subjective Visual Vertical Evaluation by a Smartphone-based Test—Taking the Phone Out of the Bucket
Authors: Wengier Anat , Ungar Omer J. , Handzel Ophir , Cavel Oren , Oron Yahav
Published: December 2020

Objective:

To measure the subjective visual vertical (SVV) in patients suffering from peripheral vestibular disorders versus controls, using a smartphone-based test designed to simulate the bucket test, in order to validate it as an available tool for the clinician.

Study design:

Prospective cohort study.

Setting:

Academic tertiary medical center.

Patients:

Forty-five adult patients were recruited to the study, 25 had vestibular disorders, and 20 did not (controls).

Intervention:

All patients underwent conventional bucket-SVV (b-SVV) and smartphone-based SVV (s-SVV) testing.

Main outcome measures:

Correlation and agreement of b-SVV and s-SVV scores in patients with peripheral vestibular disorders compared to controls.

Results:

SVV score in the vestibular disorders group was significantly higher compared to controls in both testing methods (p < 0.001 for b-SVV and p 
= 0.01 for s-SVV, effect size d = 1.7 for both testing methods). Intragroup correlation was excellent within the study group. Spearman's rank correlation coefficient between b-SVV and s-SVV was 0.902 (p 
= 0.01). Agreement measurements suggested a greater sensitivity for the b-SVV test, showing a mean difference of 1.088 degree (SD ± 1.77); directionality, however, was preserved.

Conclusion:

The smartphone-based test is a valid, simple, and efficient in-office screening tool for assisting in the diagnosis of vestibular disorders.
Factors That Influence Second-side Cochlear Implant Speech Recognition Outcomes
Authors: Dornhoffer James , Liu Yuan F. , Zhao Elise E. , Camposeo Elizabeth L. , Meyer Ted A. , McRackan Theodore R.
Published: December 2020

Objective:

Assess relationships between patient, hearing, and cochlear implant (CI)-related factors and second-side CI speech recognition outcomes in adults who are bilaterally implanted.

Study Design:

Retrospective review of a prospectively maintained CI database.

Setting:

Tertiary academic center.

Patients:

One hundred two adults receiving bilateral sequential or simultaneous CIs.

Outcome Measures:

Postimplantation consonant-nucleus-consonant (CNC) word and AzBio sentence scores at ≥12 months.

Results:

Of patient, hearing and CI-specific, factors examined only postimplantation speech recognition scores of the first CI were independently associated with speech recognition performance of the second CI on multivariable regression analysis (CNC: ß = 0.471[0.298, 0.644]; AzBio: ß = 0.602[0.417, 0.769]). First-side postoperative CNC scores explained 24.3% of variation in second CI postoperative CNC scores, while change in first CI AzBio scores explained 40.3% of variation in second CI AzBio scores. Based on established 95% confidence intervals, 75.2% (CNC) and 65.9% (AzBio) of patients score equivalent or better with their second CI compared to first CI performance. Age at implantation, duration of hearing loss, receiving simultaneous versus sequential CIs, and preoperative residual hearing (measured by pure-tone average and aided speech recognition scores) were not associated with 12 month speech recognition scores at 12 months.

Conclusions:

The degree of improvement in speech recognition from first CI may predict speech recognition with a second CI. This provides preliminary evidence-based expectations for patients considering a second CI. Counseling should be guarded given the remaining unexplained variability in outcomes. Nonetheless, these data may assist decision making when considering a second CI versus continued use of a hearing aid for an unimplanted ear.

Level of Evidence:

III
Usefulness of the Video Head Impulse Test for the Evaluation of Vestibular Function in Patients With Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
Authors: Fujiwara Keishi , Morita Shinya , Fukuda Atsushi , Yanagi Hiroko , Hoshino Kimiko , Nakamaru Yuji , Homma Akihiro
Published: December 2020

Objectives:

To investigate usefulness of the video Head Impulse Test (vHIT) as a method for evaluating semicircular canal function in patients with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV).

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

Fourteen patients with OMAAV underwent vestibular examination.

Main Outcome Measures:

The gain in vestibulo-ocular reflex (VOR) and the presence of catch-up saccade were examined for each semicircular canal.

Results:

Seven (50.0%) of the 14 patients felt subjective symptoms of disequilibrium. Dysfunction in at least one semicircular canal was detected in all ears of the OMAAV patients evaluated by vHIT. Dysfunction in posterior semicircular canal was detected more frequently than that in the anterior or horizontal canal. There were no significant correlations between the gain in VOR and hearing loss.

Conclusions:

vHIT is thought to be the most suitable method for evaluating semicircular canal function in patients with OMAAV as vHIT is not influenced by middle ear pathology and was able to evaluate vertical canal function including the posterior canal.
Attitudes of Potential Participants Towards Potential Gene Therapy Trials in Autosomal Dominant Progressive Sensorineural Hearing Loss
Authors: Levie Camille , Moyaert Julie , Janssens de Varebeke Sebastien , Verdoodt Dorien , Vanderveken Olivier M. , Topsakal Vedat , Van Wijk Erwin , de Vrieze Erik , Pennings Ronald , Van de Berg Raymond , Van Camp Guy , Ponsaerts Peter , Van Rompaey Vincent
Published: December 2020

Background:

Advances in gene therapeutic approaches to treat sensorineural hearing loss (SNHL) confront us with future challenges of translating these animal studies into clinical trials. Little is known on patient attitudes towards future innovative therapies.

Objective:

We aimed to better understand the willingness of patients with progressive SNHL and vestibular function loss of autosomal dominant (AD) inheritance to participate in potential gene therapy trials to prevent, stabilize, or slow down hearing loss.

Methods:

A survey was performed in carriers of the P51S and G88E pathogenic variant in the COCH gene (DFNA9). Various hypothetical scenarios were presented while using a Likert scale.

Results:

Fifty three participants were included, incl. 49 symptomatic patients, one presymptomatic patient, and three participants at risk. Their attitude towards potential trials studying innovative therapies was overall affirmative, even if the treatment would only slow down the decline of hearing and vestibular function, rather than cure the disease. Among the different potential scenarios, the less invasive and less frequent treatments increased the likelihood to enroll. Daily oral medication and annual intravenous infusion were awarded the highest scores. The more invasive, more frequent, and more at-risk treatments were still likely to be accepted but decreased the willingness to participate. The presence of a placebo arm was met with the lowest scores of willingness to participate.

Conclusions:

Overall, most symptomatic DFNA9 patients would likely consider participation in future innovative inner ear therapy trials, even if it would only slow down the decline of hearing and vestibular function.
Point Prevalence of Gastrostomy in a Paediatric Population
Authors: Pardy Caroline , Kharma Nasir , Lau Rachel , Kelly Veronica , Yardley Iain
Published: December 2020

Objective:

The aim of the study was to determine the prevalence of gastrostomy in a paediatric population.

Methods:

A population‐based cross‐sectional point prevalence study of paediatric gastrostomy was performed. Patients included were ages 0 to 19 years, living within 3 inner‐city London boroughs; Southwark, Lambeth, and Lewisham. Patients were identified as having a gastrostomy in situ via Home Enteral Nutrition (HEN) and community nursing databases. Electronic healthcare records were scrutinised to confirm current use of a gastrostomy. The main outcome measures were the point prevalence of gastrostomy in the paediatric population (gastrostomies/100,000 children), primary diagnosis, indication underlying gastrostomy insertion, and age at insertion.

Results:

The total population studied was 946,709, of whom 213,920 were of age 0 to 19 years. Of these, 179 had a gastrostomy in situ giving a point prevalence for gastrostomy in the paediatric population of 83.7 (95% confidence interval [CI]: 71.4–96.0)/100,000 children. This varied between age groups: 0 to 4 years: 79.6 (57.3–102.0)/100,000, 5 to 9 years: 116.3 (88.7–143.9)/100,000, 10 to 14: years 87.9 (61.9–113.9)/100,000 and 15 to 19: years 41.4 (22.1–60.1)/100,000. The most common primary diagnoses were neurological disorders (57.1%), and structural abnormalities (16.2%). Unsafe swallow was the most common indication (61%), followed by nutritional or fluid supplementation (28.6%), and behavioural reasons (8.7%). The majority (85.1%) of gastrostomies were inserted under the age of 2 years.

Conclusions:

This is the first UK population‐based study of paediatric gastrostomy, identifying a point prevalence of 84/100,000 children. The peak prevalence is in children ages 5 to 9 years. Gastrostomy insertion after a child reaches school age is uncommon.
Elongated Styloid Process With Skeletal Mandibular Protrusion
Authors: Shimizu Takahiro , Yokoo Satoshi , Takayama Yu , Musha Atsushi , Ogawa Masaru , Makiguchi Takaya
Published: December 2020

An elongated styloid process (ESP) causes symptoms such as pharyngeal pain, swallowing pain, and discomfort during mouth opening. The main treatment is surgical resection of the ESP. The authors present a case of ESP with skeletal mandibular protrusion. Because mandibular setback by sagittal splitting ramus osteotomy (SSRO) may lead to deterioration of symptoms of ESP, resection of ESP and bilateral SSRO were performed simultaneously. The patient was a 50-year-old man who visited our department with chief complaints of mandibular protrusion and pain in the left pharynx on mouth opening and swallowing. A lateral cephalogram helped in diagnosis of skeletal mandibular protrusion. In addition, an approximately 42-mm left styloid process elongated inferomedially was observed. Left styloidectomy was first performed via the cervical approach, followed by SSRO. Occlusion, facial appearance, and preoperative symptoms due to the ESP improved after surgery. The cervical appearance was esthetically satisfactory. In a case of ESP with skeletal mandibular protrusion with potential aggravation of symptoms because of mandibular setback of the ESP, resection of the styloid process is necessary together with orthognathic surgery.
The EurValve model execution environment
Authors: Bubak M. , Czechowicz K. , Gubała T. , Hose D. R. , Kasztelnik M. , Malawski M. , Meizner J. , Nowakowski P. , Wood S.
Published: December 2020

The goal of this paper is to present a dedicated high-performance computing (HPC) infrastructure which is used in the development of a so-called reduced-order model (ROM) for simulating the outcomes of interventional procedures which are contemplated in the treatment of valvular heart conditions. Following a brief introduction to the problem, the paper presents the design of a model execution environment, in which representative cases can be simulated and the parameters of the ROM fine-tuned to enable subsequent deployment of a decision support system without further need for HPC. The presentation of the system is followed by information concerning its use in processing specific patient cases in the context of the EurValve international collaboration.
Implementation of novel and conventional outbreak control measures in managing a COVID-19 outbreak in a large UK prison
Authors: Coleman Paul , Gajraj Roger , Chandan Joht Singh , Roy Anjana , Lumby Victoria , Taylor Anna , Newton Paul , Swindells Jonathan , O'Moore Eamonn
Published: December 2020

Background: SARS-CoV-2 can spread rapidly within correctional facilities. On 22nd March 2020, following identification of a confirmed COVID-19 case in a prisoner in Prison A (UK), an Outbreak Control Team was convened consisting of prison staff and public health experts from Public Health England and the UK National Health Service.

Methods: At the start of the outbreak, four prisoners and 40 staff were isolating with COVID-19 symptoms. An outbreak was declared and full prison lockdown implemented.
Prompt implementation of novel outbreak control measures prevented an explosive prison outbreak, specifically establishment of dedicated isolation and cohorting units, including (i) Reverse Cohorting Units (RCUs) for accommodating new detainees; (ii) Protective Isolation Units (PIUs) for isolating symptomatic prisoners (new detainees and existing residents), and (iii) Shielding Units (SUs) to protect medically vulnerable prisoners.

Findings: In total, 120 probable and 25 confirmed cases among prisoners and staff were recorded between March and June 2020. Among prisoners, there were six possible, 79 probable, and three confirmed cases. Among staff, there were 83 possible, 79 probable, and 22 confirmed cases. Testing of symptomatic prisoners was limited for most of the outbreak, with only 33% of probable cases tested. This explains the low number of confirmed cases (three) among prisoners despite the large number of probable cases (n=81; 92%). Over 50% of the initial cases among prisoners were on the two wings associated with the index case.

Interpretation: Rapid transmission of SARS-COV-2 was prevented through proactive steps in identifying and isolating infected prisoners (and staff), cohorting new admissions and shielding vulnerable individuals. These novel and cost-effective approaches can be implemented in a wide range of correctional facilities globally and proved effective even in the absence of mass testing.
SARS-CoV-2-specific humoral and cellular immunity in renal transplant and haemodialysis patients treated with convalescent plasma
Authors: Lindemann Monika , Krawczyk Adalbert , Dolff Sebastian , Konik Margarethe , Rohn Hana , Platte Maximillian , Thümmler Laura , Schwarzkopf Sina , Schipper Leonie , Bormann Maren , van de Sand Lukas , Breyer Marianne , Klump Hannes , Knop Dietmar , Lenz Veronika , Temme Christian , Dittmer Ulf , Horn Peter A. , Witzke Oliver
Published: December 2020

Background

When patients with chronic kidney disease are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) they can face two specific problems: Virus-specific immune responses may be impaired and remdesivir, an antiviral drug described to shorten the time to recovery, is contraindicated. Antiviral treatment with convalescent plasma could be an alternative treatment option.

Methods

In this case series we present two kidney transplant recipients and two patients dependent on haemodialysis who were infected with SARS-CoV-2 and received convalescent plasma. Antibodies against the spike 1 protein of SARS-CoV-2 were determined sequentially by IgG ELISA and neutralization assay and specific T cell responses by interferon-gamma ELISpot.

Results

Prior to treatment, in three patients antibodies were undetectable by ELISA (ratio < 1.1), corresponding to low neutralizing antibody titers (≤ 1:40). One patient was also negative to the ELISpot and two showed weak responses. After convalescent plasma treatment we observed an increase of SARS-CoV-2-specific antibodies (IgG ratio and neutralization titer) and of specific T cell responses. After intermittent clinical improvement one kidney transplant recipient again developed typical symptoms at day 12 after treatment and received a second cycle of convalescent plasma treatment. Altogether, three patients clinically improved and could be discharged from hospital. However, one multimorbid female in her early eighties deceased.

Conclusions

Our data suggest that the success of convalescent plasma therapy may only be temporary in patients with chronic kidney disease; which requires an adaptation of the treatment regimen. Close monitoring after treatment is needed for this patient group.
Impact of Nasopharyngeal Specimen Quality on SARS-CoV-2 Test Sensitivity
Authors: Richard-Greenblatt Melissa , Ziegler Matthew J. , Bromberg Valerie , Huang Elizabeth , Abdallah Hatem , Tolomeo Pam , Lautenbach Ebbing , Glaser Laurel , Kelly Brendan J.
Published: December 2020

Background

The SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) cycle of threshold (Ct) has been used to estimate quantitative viral load, with the goal of targeting isolation precautions for individuals with COVID-19 and guiding public health interventions. However, variability in specimen quality can alter the Ct values obtained from SARS-CoV-2 clinical assays. We sought to define how variable nasopharyngeal (NP) swab quality impacts clinical SARS-CoV-2 test sensitivity.

Methods

We performed amplification of a human gene target (β-actin) in parallel with a clinical RT-PCR targeting the SARS-CoV-2ORF1abgene for 1311 NP specimens collected from patients with clinical concern for COVID-19. We evaluated the relationship between NP specimen quality, characterized by high Ct values for the human gene target β-actin Ct, and the probability of SARS-CoV-2 detection via logistic regression, as well as the linear relationship between SARS-CoV-2 and β-actin Ct.

Results

Low quality NP swabs are less likely to detect SARS-CoV-2 (odds ratio 0.654, 95%CI 0.523 to 0.802). We observed a positive linear relationship between SARS-CoV-2 and β-actin Ct values (slope 0.169, 95%CI 0.092 to 0.247). COVID-19 disease severity was not associated with β-actin Ct values.

Conclusions

Variability in NP specimen quality accounts for significant differences in the sensitivity of clinical SARS-CoV-2 assays. If unrecognized, low quality NP specimens, which are characterized by a low level of amplifiable human DNA target, may limit the application of SARS-CoV-2 Ct values to direct infection control and public health interventions.
The trade-off between mobility and vaccination for COVID-19 control: a metapopulation modeling approach
Authors: Saldaña Fernando , Velasco-Hernández Jorge X.
Published: December 2020

November 2020 received a string of encouraging results from leading vaccine developers raising hopes for the imminent availability of an effective and safe vaccine against the SARS-CoV-2. In the present work, we discuss the theoretical impact of introducing a vaccine across a range of scenarios. In particular, we investigate how vaccination coverage, efficacy, and delivery time affect the control of the transmission dynamics in comparison to mobility restrictions. The analysis is based on a metapopulation epidemic model structured by risk. We perform a global sensitivity analysis using the Sobol method. Our analysis suggest that the reduction of mobility among patches play a significant role in the mitigation of the disease close to the effect of immunization coverage of 30% achieved in 4 months. Moreover, for an immunization coverage between 20%-50% achieved in the first half of 2021 with a vaccine efficacy between 70%-95%, the percentage reduction in the total number of SARS-CoV-2 infections is between 30%-50% by the end of 2021 in comparison with the no vaccination scenario.
PD-L1 – PD-1 interactions limit effector Treg cell populations at homeostasis and during infection
Authors: Perry J.A. , Clark J.T. , Gullicksrud J. , DeLong J. , Shallberg L. , Douglas B. , Hart A. , Konradt C. , Park J. , Glatman-Zaretzky A. , de Waal Malefyt R. , Christian D.A. , Sharpe A. H. , Hunter C.A.
Published: December 2020

While much is known about the factors that promote the development of diverse Treg cell responses, less is known about the pathways that constrain Treg cell activities. The studies presented here reveal that at homeostasis there is a population of effector Treg cells that express PD-1, and that blockade of PD-L1 or loss of PD-1 results in increased Treg cell activity. In response to infection with the parasiteT. gondii, the early production of IFN-γ results in widespread upregulation of PD-L1. Moreover, blockade of PD-L1, whole body deletion of PD-1, or lineage-specific deletion of PD-1 in Foxp3+cells prevented the loss of the effector Treg cells but resulted in reduced pathogen specific CD4+T cell responses during infection. Thus, at homeostasis basal PD-L1 expression constrains and tunes the pool of Treg cells, but during infection the upregulation of PD-L1 provides a mechanism to contract the Treg cell population required to maximize the development of pathogen specific CD4+T cell responses.
Plasma glutathione status as indicator of pre-analytical centrifugation delay
Authors: Tomin Tamara , Bordag Natalie , Zügner Elmar , Al-Baghdadi Abdullah , Schinagl Maximillian , Birner-Gruenberger Ruth , Schittmayer Matthias
Published: December 2020

Prolonged incubation of blood prior to plasma preparation can significantly influence the quality of the resulting data. Different markers for this pre-clinical variability have been proposed over the years but with limited success.

In this study we explored the usefulness of glutathione (GSH) status, namely ratio of reduced to oxidized glutathione (GSH/GSSG), as potential marker of plasma preparation delay. For that purpose, blood from 20 healthy volunteers was collected into tubes with a cysteine quencher (N-ethylmaleimide; NEM) for GSH stabilization. Plasma preparation was delayed at room temperature for up to 3 hours and every hour, a plasma sample was prepared and the GSH/GSSG ratio measured.

We report that over the course of the investigation, plasma concentrations of both GSH and GSSG increased linearly (R2= 0.99 and 0.98, respectively). Since GSH increased at a much faster rate compared to GSSG, the GSH/GSSG ratio also increased linearly in a time dependent manner (R2= 0.99). As GSH is an intracellular antioxidant, we speculated that this might stem from ongoing blood hemolysis, which was confirmed by the time dependent rise in lactate dehydrogenase (LDH) activity in the plasma samples. Moreover, we demonstrate that the addition of the thiol alkylating reagent NEM directly to the blood tubes does not seem to influence downstream analysis of clinical parameters. In conclusion we propose that the glutathione status could be used as an indicator of the centrifugation delay prior to plasma preparation.
Role of left motor cortex in post-stroke fatigue: a corticospinal excitability study
Authors: De Doncker William , Kuppuswamy Annapoorna
Published: December 2020

Background

The neural mechanisms that underlie post-stroke fatigue are poorly understood. Previous work show an inverse relationship between motor cortex excitability and post-stroke fatigue, however, it is unclear if the side of lesion influences this relationship. The left hemisphere plays a dominant role in motor control, therefore we hypothesised that left hemisphere strokes are more likely to show a significant inverse relationship between corticospinal excitability and fatigue.

Methods

Resting motor threshold (measure of corticospinal excitability) using transcranial magnetic stimulation was measured in the affected hemisphere of 98 stroke survivors. Fatigue was measured using the fatigue severity scale. The effect of fatigue and hemisphere affected on corticospinal excitability was analysed using a multiple linear regression.

Results

A multiple linear regression with trait fatigue as the outcome variable (F(4,93)=12.04, p < 0.001, adj R2= 0.313) revealed that RMT was not a significant predictor of FSS-7 (β = −0.063, p = 0.706, CI[-0.394, 0.268]), while the interaction between lesioned hemisphere and RMT was a significant predictor of FSS-7 (β = 0.339, p = 0.039, CI[0.018, 0.659]). The additional explanatory variables of HADSDepressionand sex were also significant predictors of FSS-7 (β = 903, p < 0.001, CI[0.584, 1.223] and β = 1.127, p = 0.002, CI[0.425, 1.830] respectively).

Conclusion

Lower corticospinal excitability of the left hemisphere may indicate altered perception of effort and reduced sensory attenuation. This provides evidence to support the sensory attenuation model of fatigue.
Single-cell RNA sequencing reveals time- and sex-specific responses of spinal cord microglia to peripheral nerve injury and links ApoE to neuropathic pain
Authors: Tansley Shannon , Uttam Sonali , Ureña Guzmán Alba , Yaqubi Moein , Pacis Alain , Parisien Marc , Rabau Oded , Haglund Lisbet , Ouellet Jean , Santaguida Carlo , Ragoussis Jiannis , Zhang Ji , Salter Michael W , Diatchenko Luda , Healy Luke M. , Mogil Jeffrey S. , Khoutorsky Arkady
Published: December 2020

Activation of microglia in the spinal cord following peripheral nerve injury is critical for the development of long-lasting pain hypersensitivity. However, it remains unknown whether distinct microglia subpopulations or states contribute to different stages of pain development and maintenance. We show, using single-cell RNA-sequencing, that nerve injury induces the generation of a male-specific inflammatory microglia subtype, and demonstrate increased proliferation of microglia in males as compared to females. We also show time- and sex-specific transcriptional changes in different microglial subpopulations following injury. Apolipoprotein E (Apoe) is the top upregulated gene in microglia at chronic time points after nerve injury in mice and polymorphisms in theAPOEgene in humans are associated with chronic pain. Single-cell analysis of human spinal cord microglia reveals a subpopulation with a disease-related transcriptional signature. Our data provide a detailed analysis of transcriptional states of mouse and human spinal cord microglia, and identify a previously unrecognized role for ApoE in neuropathic pain.
COVID-19 Spreading Dynamics with Vaccination – Allocation Strategy, Return to Normalcy and Vaccine Hesitancy
Authors: Shayak B , Sharma Mohit M
Published: December 2020

In this work we use mathematical modeling to analyse the dynamics of COVID-19 spread after a vaccination program is initiated. The model used is a delay differential equation developed earlier by our group. Basis of currently available data, our principal findings are as follows. (a) For fastest deceleration of the pandemic, people with high interaction rate such as grocers and airline cabin crew should be given priority in vaccine access. (b) Individuals who have been vaccinated may be selectively cleared to return to normal activities without significant risk of a resurgence in cases. (c) If an infection as well as a vaccine confers immunity for a duration τ0, then the pandemic can be eliminated by vaccinating people at a sufficiently high rate. Unless τ0 is very small, the cutoff rate required appears feasible to achieve in practice. (d) The presence of a substantial minority of vaccine-hesitant population might not amount to a significant threat or even an inconvenience to a vaccine-compliant majority population.
A membrane-associated condensate drives paternal epigenetic inheritance inC. elegans
Authors: Schreier Jan , Dietz Sabrina , de Jesus Domingues Antonio M. , Seistrup Ann-Sophie , Nguyen Dieu An H. , Gleason Elizabeth J. , Ling Huiping , L’Hernault Steven W. , Phillips Carolyn M. , Butter Falk , Ketting René F.
Published: December 2020

Transgenerational epigenetic inheritance (TEI) describes the transmission of gene-regulatory information across generations without altering DNA sequences, and allows priming of offspring towards transposable elements (TEs) and changing environmental conditions. One important mechanism that acts in TEI is based on small non-coding RNAs. Whereas factors for maternal inheritance of small RNAs have been identified, paternal inheritance is poorly understood, as much of the cellular content is extruded during spermatogenesis. We identify a phase separation-based mechanism, driven by the protein PEI-1, which is characterized by a BTB-BACK domain and an intrinsically disordered region (IDR). PEI-1 specifically secures the Argonaute protein WAGO-3 within maturing sperm inC. elegans. Localization of PEI granules in mature sperm is coupled, via S-palmitoylation, to myosin-driven transport of membranous organelles.pei-1-like genes are also found in human and often expressed in testis, suggesting that the here identified mechanism may be broadly conserved.
AcquiredRAD51Cpromoter methylation loss causes PARP inhibitor resistance in high grade serous ovarian carcinoma
Authors: Nesic Ksenija , Kondrashova Olga , Hurley Rachel M. , McGehee Cordelia , Vandenberg Cassandra J , Ho Gwo-Yaw , Lieschke Elizabeth , Dall Genevieve , Bound Nirashaa , Shield-Artin Kristy , Radke Marc , Musafer Ashan , Chai Zi Qing , Ghamsari Mohammad Reza Eftekhariyan , Harrell Maria I. , Kee Damien , Olesen Inger , McNally Orla , Traficante Nadia ,   Australian Ovarian Cancer Study, DeFazio Anna , Bowtell David D. , Swisher Elizabeth M. , Weroha S. John , Nones Katia , Waddell Nicola , Kaufmann Scott H. , Dobrovic Alexander , Wakefield Matthew J. , Scott Clare L. ,   Australian Ovarian Cancer Study (AOCS)
Published: December 2020

While loss ofBRCA1promoter methylation has been shown to cause PARP inhibitor (PARPi) resistance in high-grade serous ovarian carcinoma (HGSC), the impacts ofRAD51Cmethylation (meRAD51C) remain unresolved. In this study, three PARPi-responsive HGSC patient-derived xenografts (PDX) withRAD51Cgene silencing and homologous recombination deficiency were found to have either homogeneous or heterogeneous patterns of meRAD51C. PDX could lose meRAD51Cfollowing PARPi treatment (rucaparib/niraparib), where a single unmethylatedRAD51Ccopy was sufficient to drive PARPi-resistance. Genomic profiling revealed this resistance was acquired independently in two distinct PDX lineages. Furthermore, we describe a patient sample where 1/3RAD51Cgene copies lost methylation following neoadjuvant chemotherapy. We show meRAD51Cis a positive predictive biomarker for PARPi response and should be screened for routinely in patients. However, methylation loss in a single gene copy is sufficient to cause PARPi resistance and should be carefully assessed in previously treated patients considering PARPi therapy.
Crystal structure, Hirshfeld surface analysis, DFT and molecular docking investigation of 2-(2-oxo-1,3-oxazolidin-3-yl)ethyl 2-[2-(2-oxo-1,3-oxazolidin-3-yl)ethoxy]quinoline-4-carboxylate
Authors: Bouzian Younos , Baydere Cemile , Dege Necmi , Ahabchane Noureddine Hamou , Mague Joel T. , Abudunia Abdulmalik , Karrouchi Khalid , Essassi El Mokhtar
Published: December 2020

In the molecular structure of the title compound, C20H21N3O7, the quinoline ring system is slightly bent, with a dihedral angle between the phenyl and the pyridine rings of 3.47 (7)°. In the crystal, corrugated layers of molecules extending along the ab plane are generated by C—H...O hydrogen bonds. The intermolecular interactions were quantified by Hirshfeld surface analysis and two-dimensional fingerprint plots. The most significant contributions to the crystal packing are from H...H (42.3%), H...O/O...H (34.5%) and H...C/ C...H (17.6%) contacts. Molecular orbital calculations providing electron-density plots of the HOMO and LUMO as well as molecular electrostatic potentials (MEP) were computed, both with the DFT/B3LYP/6–311 G++(d,p) basis set. A molecular docking study between the title molecule and the COVID-19 main protease (PDB ID: 6LU7) was performed, showing that it is a good agent because of its affinity and ability to adhere to the active sites of the protein.
Crystal structure, Hirshfeld surface analysis and energy framework study of 6-formyl-7,8,9,11-tetrahydro-5H-pyrido[2,1-b]quinazolin-11-one
Authors: Tojiboev Akmal , Zhurakulov Sherzod , Vinogradova Valentina , Englert Ulli , Wang Ruimin
Published: December 2020

At 100 K, the title compound, C13H12N2O2, crystallizes in the orthorhombic space group Pna21 with two very similar molecules in the asymmetric unit. An intramolecular N—H...O hydrogen bond leads to an S(6) graph-set motif in each of the molecules. Intermolecular π–π stacking and C=O...π interactions involving the aldehyde O atoms link molecules into stacks parallel to [100]. A Hirshfeld surface analysis indicates that the most important contributions to the crystal packing stem from H...H (49.4%) and H...O/O...H (21.5%) interactions. Energy framework calculations reveal a significant contribution of dispersion energy. The crystal studied was refined as a two-component inversion twin.