bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomedical Computational Linguistics and Natural Language Processing
Authors: Cohen Kevin Bretonnel
Published: April 2021

Computational linguistics has its origins in the post-Second World War research on translation of Russian-language scientific journal articles in the United States. Today, biomedical natural language processing treats clinical data, the scientific literature, and social media, with use cases ranging from studying adverse effects of drugs to interpreting high-throughput genomic assays (Névéol and Zweigenbaum 2018). Many of the most prominent research areas in the field involve extracting information from text and normalizing it to enormous databases of domain-relevant semantic classes, such as genes, diseases, and biological processes. Moving forward, the field is expected to play a significant role in understanding reproducibility in natural language processing.
Quare Times: An Introduction to a Queer Perspective on Afrofuturism and a Reading of Sun Ra’s Space Is the Place
Authors: Stüttgen Tim
Published: April 2021

The film Space Is the Place (1974), directed by John Coney, stars Sun Ra who was also co-author of the script. This chapter explores Sun Ra’s Afrofuturism as shown in the film, bringing it into relation with José Muñoz’s notion of a queer future. Rather than focusing on Sun Ra’s sexuality, this chapter argues that his quareness (E. Patrick Johnson’s useful term drawn from African American vernacular) emerges in the sonic and performative aspects of his work. Sun Ra’s spaceship offers a future-oriented response to the slave ship and Middle Passage (as described by Paul Gilroy) and to the limitations of the here and now. The notion of assemblage (Gilles Deleuze and Felix Guattari) articulates the quareness of Sun Ra’s collective improvisational practices.
Anticolonial Terrorism
Authors: Sedgwick Mark
Published: April 2021

This chapter looks at the rise of anticolonial terrorism in Egypt, and especially at the role played by the Egyptian Muslim Brotherhood. It argues that assassination became established among anticolonial nationalists in Egypt before the Brotherhood was founded and was then briefly practiced by the Brotherhood. The Brotherhood, however, generally preferred other varieties of violence, which it understood as jihad. Some of these were more obviously acts of political violence than others. The use of violence was never part of the Brotherhood’s main strategy, however, and in the end it proved disastrous for them. They definitively abandoned terrorism in about 1968.
Lack of Support for the Genes by Early Environment Interaction Hypothesis in the Pathogenesis of Schizophrenia
Authors: Vassos Evangelos , Kou Jiaqi , Tosato Sarah , Maxwell Jessye , Dennison Charlotte A , Legge Sophie E , Walters James T R , Owen Michael J , O’Donovan Michael C , Breen Gerome , Lewis Cathryn M , Sullivan Patrick F , Hultman Christina , Ruggeri Mirella , Walshe Muriel , Bramon Elvira , Bergen Sarah E , Murray Robin M
Published: April 2021

Ursini et al reported recently that the liability of schizophrenia explained by a polygenic risk score (PRS) derived from the variants most associated with schizophrenia was increased 5-fold in individuals who experienced complications during pregnancy or birth. Follow-up gene expression analysis showed that the genes mapping to the most associated genetic variants are highly expressed in placental tissues. If confirmed, these findings will have major implications in our understanding of the joint effect of genes and environment in the pathogenesis of schizophrenia. We examined the interplay between PRS and obstetric complications (OCs) in 5 independent samples (effective N = 2110). OCs were assessed with the full or modified Lewis-Murray scale, or with birth weight < 2.5 kg as a proxy. In a large cohort we tested whether the pathways from placenta-relevant variants in the original report were associated with case-control status. Unlike in the original study, we did not find significant effect of PRS on the presence of OCs in cases, nor a substantial difference in the association of PRS with case-control status in samples stratified by the presence of OCs. Furthermore, none of the PRS by OCs interactions were significant, nor were any of the biological pathways, examined in the Swedish cohort. Our study could not support the hypothesis of a mediating effect of placenta biology in the pathway from genes to schizophrenia. Methodology differences, in particular the different scales measuring OCs, as well as power constraints for interaction analyses in both studies, may explain this discrepancy.
The natural history of insomnia: predisposing, precipitating, coping, and perpetuating factors over the early developmental course of insomnia
Authors: Ellis Jason G , Perlis Michael L , Espie Colin A , Grandner Michael A , Bastien Célyne H , Barclay Nicola L , Altena Ellemarije , Gardani Maria
Published: April 2021

While there is an extensive literature on predisposing, precipitating, coping, and perpetuating factors in those with chronic insomnia, very little work has been undertaken to evaluate these factors over the early developmental course of insomnia. The present aim was to determine whether several hypothesized factors in each domain (predisposing, precipitating, coping, and perpetuating), assessed during an episode of acute insomnia (AI), are related to its persistence or remission to normal sleep. Participants comprised n = 140 people with AI and n = 737 normal sleepers (NS) recruited from the general public. Participants completed measures assessing predisposing characteristics (personality traits, arousal predisposition, and insomnia vulnerability), precipitating events and outcomes (life events, perceived stress, anxiety, and depression), coping styles (thought control strategies and coping styles), and perpetuating factors (sleep preoccupation, pre-sleep arousal, dysfunctional beliefs, and fatigue). Additionally, insomnia status (from AI at baseline to its persistence or natural remission [NR]) was assessed 1 month later (n = 129). Baseline differences between NS and individuals with AI were observed in each domain with increasing age, lower openness to experience and conscientiousness, higher insomnia severity, levels of anxiety, and affective sleep preoccupation significantly predicting AI status. Further, a previous episode of insomnia, higher depression scores, and affective sleep preoccupation scores significantly predicted its persistence, as opposed to its NR. Results are discussed with reference to the conceptualization of insomnia and how the findings may influence the design of preventative interventions to circumvent the transition from acute to chronic insomnia.
Metatranscriptomic Comparison of Endophytic and Pathogenic Fusarium–Arabidopsis Interactions Reveals Plant Transcriptional Plasticity
Authors: Guo Li , Yu Houlin , Wang Bo , Vescio Kathryn , DeIulio Gregory A. , Yang He , Berg Andrew , Zhang Lili , Edel-Hermann Véronique , Steinberg Christian , Kistler H. Corby , Ma Li-Jun
Published: April 2021

Plants are continuously exposed to beneficial and pathogenic microbes, but how plants recognize and respond to friends versus foes remains poorly understood. Here, we compared the molecular response of Arabidopsis thaliana independently challenged with a Fusarium oxysporum endophyte Fo47 versus a pathogen Fo5176. These two F. oxysporum strains share a core genome of about 46 Mb, in addition to 1,229 and 5,415 unique accessory genes. Metatranscriptomic data reveal a shared pattern of expression for most plant genes (about 80%) in responding to both fungal inoculums at all timepoints from 12 to 96 h postinoculation (HPI). However, the distinct responding genes depict transcriptional plasticity, as the pathogenic interaction activates plant stress responses and suppresses functions related to plant growth and development, while the endophytic interaction attenuates host immunity but activates plant nitrogen assimilation. The differences in reprogramming of the plant transcriptome are most obvious in 12 HPI, the earliest timepoint sampled, and are linked to accessory genes in both fungal genomes. Collectively, our results indicate that the A. thaliana and F. oxysporum interaction displays both transcriptome conservation and plasticity in the early stages of infection, providing insights into the fine-tuning of gene regulation underlying plant differential responses to fungal endophytes and pathogens.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Short-, Mid-, and Long-Term Associations Between PM2.5 and Stroke Incidence in Taiwan
Authors: Yang Chun-Pai , Li Chung-Yi , Huang Winn-Jung , Yu Hwa-Lung , Yang Cheng-Chia , Lu Mei-Chun , Lang Hui-Chu , Yan Yuan-Horng
Published: April 2021

Objective:

To investigate the association between the risk of stroke and exposure to particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) over various exposure periods.

Methods:

This was a nationwide population-based case–control study in which 10,035 incident patients with a primary diagnosis of ischemic stroke each were matched with two randomly selected controls for sex, age, Charlson Comorbidity Index, year of stroke diagnosis, and level of urbanization. Multiple logistic models adjusted for potential confounders were used to assess the association of PM2.5 with ischemic stroke incidence.

Results:

There were significant short-term, medium-term, and long-term relationships between PM2.5 exposure and ischemic stroke incidence.

Conclusions:

This study supports existing evidence that PM2.5 should be considered a risk factor for ischemic stroke.
F-18 ML-104 tau PET imaging in mild cognitive impairment
Authors: Jaleel Jasim , Tripathi Madhavi , Baghel Vivek , Arunraj Sreedharan Thankarajan , Kumar Praveen , Khan Dikhra , Tripathi Manjari , Dey Aprajit Ballav , Bal Chandrasekhar
Published: April 2021

Objective

This study was undertaken to evaluate the tau distribution patterns in patients with amnestic mild cognitive impairment (aMCI) using PET radiotracer F-18 ML-104.

Materials and methods

Thirty patients, clinically diagnosed as aMCI [mini mental state evaluation ≥24] in the neurology or geriatric memory clinics, were included in the study. Each aMCI patient underwent F-18 fluorodeoxyglucose and F-18 ML-104 tau PET. Standardized uptake value ratios for cortical gray matter regions were evaluated for F-18 ML-104 tau PET and compared with normal controls and with early Alzheimer’s disease (AD) patients (used from a previous study).

Results

aMCI revealed significantly higher standardized uptake value ratios in both medial temporal cortices, precuneus and posterior cingulate cortices in comparison to normal controls and a significantly lesser binding in bilateral medial and lateral temporal, precuneus and posterior cingulate cortices in comparison to early AD. A negative correlation was noted between F-18 fluorodeoxyglucose uptake and F-18 ML-104 retention in the precuneus and posterior cingulate cortices in aMCI, while F-18 ML-104 retention and mini mental state evaluation scores revealed a moderate negative correlation in the posterior cingulate cortices.

Conclusion

We could demonstrate a significant increase in cortical tau deposition in aMCI patients in comparison to normal controls, thus providing in vivo evidence of the underlying pathological process in this subgroup of patients with high probability of conversion to AD.
Efficacy and safety of 177Lu-DOTMP in palliative treatment of symptomatic skeletal metastases: a prospective study
Authors: Bollampally Neeraja , Shukla Jaya , Mittal Bhagwant Rai , Sood Ashwani , Mohanty Manju , Kapoor Rakesh , Vatsa Rakhee , Satapathy Swayamjeet , Chakravarty Rubel , Chakraborty Sudipta , Dash Ashutosh K
Published: April 2021

Aims

Bone-seeking radiopharmaceutical 177Lu-DOTMP with favorable pharmacokinetics in the preclinical studies has been evaluated for its role in reducing bone pain and improving quality of life (QOL) in patients with symptomatic skeletal metastases.

Method

Patients with painful widespread skeletal metastases documented on 99mTc-MDP bone scintigraphy were intravenously administered 37 MBq/kg of 177Lu-DOTMP. Visual analogue score (VAS), analgesic score, European Cooperative Group of Oncology (ECOG) and the European Organization of Research and Treatment of Cancer QLQ-C30 of all the patients were assessed at baseline and posttherapy follow-up. Adverse effects were graded according to NCI-CTCAE V 5.0.

Results

Twenty-seven patients with painful widespread skeletal metastases (men 18; median age 61 years; range: 18–81) were studied for their responses as complete response, partial response, minimal response, no response and pain progression based on VAS and analgesic score. Overall response was seen in 77.8% of patients (complete, partial and minimal in 29.6, 33.3 and 14.8%, respectively) with significant improvement in median VAS and mean analgesic score at 2 months posttherapy from baseline (P < 0.001). The best response was seen in patients with breast cancer (100%) followed by prostate cancer (81%) and lung cancer (28%). Improvement in QOL was noted in 40% of patients, with change in ECOG score from 3.07 ± 0.67 at baseline to 2.6 ± 0.9 at 2 months posttherapy. Grade 2/3 anemia, grade 1/2 leukopenia and grade 1/3 thrombocytopenia were seen in 37, 11.1 and 18.5% patients respectively in the follow-up.

Conclusion

177Lu-DOTMP appears to be efficacious treatment for bone pain palliation with improvement in QOL though less effective in patients with lung cancer. The patients had transient mild–moderate hematotoxicity.
Invasive and noninvasive ventilation strategies for acute respiratory failure in children with coronavirus disease 2019
Authors: Blumenthal Jennifer A. , Duvall Melody G.
Published: April 2021

Purpose of review

Severe Acute Respiratory Syndrome Coronavirus 2 presents as symptomatic coronavirus disease 2019 (COVID-19) disease in susceptible patients. Severe pediatric COVID-19 disease is rare, limiting potential data accumulation on associated respiratory failure in children. Pediatric intensivists and pulmonologists managing COVID-19 patients look to adult guidelines and pediatric-specific consensus statements to guide management. The purpose of this article is to review the current literature and recommended strategies for the escalation of noninvasive and invasive respiratory support for acute respiratory failure associated with COVID-19 disease in children.

Recent findings

There are no prospective studies comparing COVID-19 treatment strategies in children. Adult and pediatric ventilation management interim guidance is based on evidence-based guidelines in non-COVID acute respiratory distress syndrome, with considerations of (1) noninvasive positive pressure ventilation versus high-flow nasal cannula and (2) high versus lower positive end expiratory pressure strategies related to lung compliance and potential lung recruitability.

Management of acute respiratory failure from COVID-19 requires individualized titration of noninvasive and invasive ventilation modalities with consideration of preserved or compromised pulmonary compliance. Research regarding best practices in the management of pediatric severe COVID-19 with respiratory failure is lacking and is acutely needed as the pandemic surges and vaccination of the pediatric population will be delayed compared to adults.
Sensitivity of rapid antigen testing and RT-PCR performed on nasopharyngeal swabs versus saliva samples in COVID-19 hospitalized patients: results of a prospective comparative trial (RESTART)
Authors: Kritikos Antonios , Caruana Giorgia , Brouillet René , Miroz John-Paul , Samia Abed-Maillard , Geraldine Stieger , Opota Onya , Croxatto Antony , Vollenweider Peter , Bart Pierre-Alexandre , Chiche Jean-Daniel , Greub Gilbert
Published: April 2021

Objectives

Saliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen testing (RAT) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal (NP) swabs and salivary samples.

Methods

We conducted a prospective observational study among COVID-19 hospitalized patients between 10th December 2020 and 1st February 2021. Paired saliva and NP samples were investigated by RT-PCR (Cobas 6800, Roche-Switzerland) and by two rapid antigen tests: One Step Immunoassay Exdia® COVID-19 Ag (Precision Biosensor, Korea) and Standard Q® COVID-19 Rapid Antigen Test (Roche-Switzerland).

Results

A total of 58 paired NP-saliva specimens were collected. Thirty-two of 58 (55%) patients were hospitalized in the intensive care unit and the median duration of symptoms was 11 days (IQR 5-19). NP and salivary RT-PCR exhibited sensitivity of 98% and 69% respectively whereas the specificity of these RT-PCRs assays were of 100%. NP RAT exhibited much lower diagnostic performances with sensitivities of 35% and 41% for the Standard Q® and Exdia® assays respectively, when a wet-swab approach was used (i.e. when the swab was diluted in the viral transport medium (VTM) before testing). The sensitivity of the dry-swab approach was slightly better (47%). These antigen tests exhibited very low sensitivity (4 and 8%) when applied to salivary swabs.

Conclusions

Nasopharyngeal RT-PCR is the most accurate test for COVID-19 diagnosis in hospitalized patients. RT-PCR on salivary samples may be used when nasopharyngeal swabs are contraindicated. RAT are not appropriate for hospitalized patients.
An international, interlaboratory ring trial confirms the feasibility of an open-source, extraction-less “direct” RT-qPCR method for reliable detection of SARS-CoV-2 RNA in clinical samples
Authors: Mills Margaret G. , Bruce Emily , Huang Meei-Li , Crothers Jessica W. , Hyrien Ollivier , Oura Christopher A. L. , Blake Lemar , Jordan Arianne Brown , Hester Susan , Wehmas Leah , Mari Bernard , Barby Pascal , Lacoux Caroline , Fassy Julien , Vial Pablo , Vial Cecilia , Martinez Jose R.W. , Oladipo Olusola Olalekan , Inuwa Bitrus , Shittu Ismaila , Meseko Clement A. , Chammas Roger , Santos Carlos Ferreira , José Dionísio Thiago , Garbieri Thais Francini , Parisi Viviane Aparecida , Mendes-Correa Maria Cassia , dePaula Anderson V. , Romano Camila M. , Góes Luiz Gustavo Bentim , Minoprio Paola , Campos Angelica C. , Cunha Marielton P. , Vilela Ana Paula P. , Nyirenda Tonney , Mkakosya Rajhab Sawasawa , Muula Adamson S. , Dumm Rebekah E. , Harris Rebecca M. , Mitchell Constance A. , Pettit Syril , Botten Jason , Jerome Keith R.
Published: April 2021

Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) is used worldwide to test and trace the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). “Extraction-less” or “direct” real time–reverse transcription polymerase chain reaction (RT-PCR) is an open-access qualitative method for SARS-CoV-2 detection from nasopharyngeal or oral pharyngeal samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged 10 global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international interlaboratory ring trial. Participating laboratories were provided a common protocol, common reagents, aliquots of identical pooled clinical samples, and purified nucleic acids and used their existing in-house equipment. We observed 100% concordance across laboratories in the correct identification of all positive and negative samples, with highly similar cycle threshold values. The test also performed well when applied to locally collected patient nasopharyngeal samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that open-access, direct RT-PCR assays are a feasible option for more efficient COVID-19 coronavirus disease testing as demanded by the continuing pandemic.
Plasma glial fibrillary acidic protein is an early marker of Aβ pathology in Alzheimer’s disease
Authors: Pereira Joana B. , Janelidze Shorena , Smith Ruben , Mattsson-Carlgren Niklas , Palmqvist Sebastian , Zetterberg Henrik , Stomrud Erik , Ashton Nicholas J. , Blennow Kaj , Hansson Oskar
Published: April 2021

Although recent clinical trials targeting amyloid-β (Aβ) in Alzheimer’s disease (AD) have shown promising results, there is increasing evidence suggesting that understanding alternative disease pathways that interact with Aβ metabolism and amyloid pathology might be important to halt the clinical deterioration. In particular, there is evidence supporting a critical role of astroglial activation and astrocytosis in AD. However, to this date, no studies have assessed whether astrocytosis is independently related to Aβ or tau pathology, respectively,in vivo. To address this question, we determined the levels of the astrocytic marker glial fibrillary acidic protein (GFAP) in plasma and cerebrospinal fluid (CSF) of 217 Aβ-negative cognitively unimpaired individuals, 71 Aβ-positive cognitively unimpaired individuals, 78 Aβ-positive cognitively impaired individuals, 63 Aβ-negative cognitively impaired individuals and 75 patients with a non-AD neurodegenerative disorder from the Swedish BioFINDER-2 study. Subjects underwent longitudinal Aβ (18F-flutemetamol) and tau (18F-RO948) positron emission tomography (PET) as well as cognitive testing. We found that plasma GFAP concentration was significantly increased in all Aβ-positive groups compared with subjects without Aβ pathology (p<0.01). In addition, there were significant associations between plasma GFAP with higher Aβ-PET signal in all Aβ-positive groups, but also in cognitively normal individuals with normal Aβ values (p<0.001), which remained significant after controlling for tau-PET signal. Furthermore, plasma GFAP could predict Aβ-PET positivity with an area under the curve of 0.76, which was greater than the performance achieved by CSF GFAP (0.69) and other glial markers (CSF YKL-40: 0.64, sTREM2: 0.71). Although correlations were also observed between tau-PET and plasma GFAP, these were no longer significant after controlling for Aβ-PET. In contrast to plasma GFAP, CSF GFAP concentration was significantly increased in non-AD patients compared to other groups (p<0.05) and correlated with Aβ-PET only in Aβ-positive cognitively impaired individuals (p=0.005). Finally, plasma GFAP was associated with both longitudinal Aβ-PET and cognitive decline, and mediated the effect of Aβ-PET on tau-PET burden, suggesting that astrocytosis secondary to Aβ aggregation might promote tau accumulation. Altogether, these findings indicate that plasma GFAP is an early marker associated with brain Aβ pathology but not tau aggregation, even in cognitively normal individuals with a normal Aβ status. This suggests that plasma GFAP should be incorporated in current hypothetical models of AD pathogenesis and be used as a non-invasive and accessible tool to detect early astrocytosis secondary to Aβ pathology.
Spread of the SARS-CoV-2 UK-variant in the South East of France: impact on COVID-19 patients’ age, comorbidity profiles and clinical presentation
Authors: Courjon Johan , Contenti Julie , Demonchy Elisa , Levraut Jacques , Barbry Pascal , Rios Géraldine , Dellamonica Jean , Chirio David , Bonnefoy Caroline , Giordanengo Valérie , Carles Michel
Published: April 2021

Objectives

The variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (South East of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this aera. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits.

Methods

Observational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n=1247) and those hospitalized in the infectious diseases ward or ICU (n=232). Demographic data, clinical signs and severity were recorded by the NEWS-2, SAPS-2 and SOFA scores were recorded and analyzed.

Results

the UK-variant was absent in the area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63% to 50% (p=0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p<0.001) while the proportion of patients without comorbidity increased from 16% to 42% (p=0.007). Neither the NEWS-2 score nor the main signs of clinical severity have changed over time.

Conclusion

Spread of the UK-variant in the South East of France affects younger and healthier patients.
Predicting severe COVID-19 outcomes for triage and resource allocation
Authors: Morada Anthony Onde , Scheidel Caleb , Brown Jennifer , Albright Jeremy , Kolade Victor , Cagir Burt
Published: April 2021

Background

While numerous studies have identified factors associated with severe COVID-19 outcomes, they have yet to quantify these characteristics. Therefore, our study’s purpose is to stratify these risk factors and use them to predict outcomes.

Study Design

This is a retrospective review of the CDC COVID-19 Surveillance Data. Logistic regression models calculated risk estimates for independent variables, and random forest models predicted the chance of severe outcomes.

Results

Our sample of 3,798,261 patients with COVID-19 consisted mainly of females (51.9%), 10-to 69-year-olds, and White/Non-Hispanics (34.9%). Most were not healthcare workers (90.6%) and did not have preexisting medical conditions (47.1%). Age had an increased risk of severe outcomes that grew every decade of life. White patients had a decreased occurrence of severe outcomes than Non-Whites, except for Pacific Islanders with comparable mortality. The variable selection algorithm detected that three outcomes were more accurate without healthcare worker classification: mechanical ventilation/intubation, pneumonia, and ARDS Acute respiratory distress. However, providers had a decreased risk of severe outcomes overall. Also, patients with preexisting conditions demonstrated an increased risk in all outcomes. Compared to the logistic regressions, the predictive models had a higher performance (AUC>0.8). The death model had the best metrics, followed by hospitalization and ventilation. We amassed these predictive models into the Severe COVID-19 Calculator web application that estimates the probability of severe outcomes.

Conclusions

Several patient social and medical demographics recorded by the CDC significantly affect severe COVID-19 outcomes suggesting a multifactorial influence. To account for these variables, a generated Severe Covid-19 Calculator can accurately predict the chance of severe outcomes in citizens that may contract or have COVID-19.
Deep Neural Survival Networks for Cardiovascular Risk Prediction: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Hathaway Quincy A. , Yanamala Naveena , Budoff Matthew J. , Sengupta Partho P. , Zeb Irfan
Published: April 2021

Background

There is growing interest in utilizing machine learning techniques for routine atherosclerotic cardiovascular disease (ASCVD) risk prediction. We investigated whether novel deep learning survival models can augment ASCVD risk prediction over existing statistical and machine learning approaches.

Methods

6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed over 16 years to assess incidence of all-cause mortality (mortality) or a composite of major adverse events (MAE). Features were evaluated within the categories of traditional risk factors, inflammatory biomarkers, and imaging markers. Data was split into an internal training/testing (four centers) and external validation (two centers). Both machine learning (COXPH, RSF, and lSVM) and deep learning (nMTLR and DeepSurv) models were evaluated.

Results

In comparison to the COXPH model, DeepSurv significantly improved ASCVD risk prediction for MAE (AUC: 0.82 vs. 0.79, P≤0.001) and mortality (AUC: 0.86 vs. 0.80, P≤0.001) with traditional risk factors alone. Implementing non-categorical NRI, we noted a 65% increase in correct reclassification compared to the COXPH model for both MAE and mortality (P≤0.05). Assessing the relative risk of participants, DeepSurv was the only learning algorithm to develop a significantly improved risk score criteria, which outcompeted COXPH for both MAE (4.07 vs. 2.66, P≤0.001) and mortality (6.28 vs. 4.67, P=0.014). The addition of inflammatory or imaging biomarkers to traditional risk factors showed minimal/no significant improvement in model prediction.

Conclusion

DeepSurv can leverage simple office-based clinical features alone to accurately predict ASCVD risk and cardiovascular outcomes, without the need for additional features, such as inflammatory and imaging biomarkers.
How to tie dangerous surgical knots – easily. Can we avoid this?
Authors: Drabble E H , Spanopoulou S , Sioka E. , Politaki E , Paraskeva I K , Palla E , Stockley L , Zacharoulis D
Published: April 2021

Objective

Secure knots are essential. Previous publications have concentrated on security of different knot types, but could individual technique be important?

Determine whether the technique of formation of each layer of a surgical knot is important to the security of the knot formed.

Design study

Prospective analysis of technique on knot security

Materials and methods

Senior and resident surgeons, and medical students, tied knots with three techniques, using four study materials, 2/0 polyglactin 910 (vicryl), 3/0 polydioxanone (PDS), 4/0 poliglecaprone 25 (monocryl) and 1 nylon (Ethilon); a standard flat reef knot (FRK), knots tied under tension (TK), and knots laid without appropriate hand crossing (NHCK). Each knot technique was performed reproducibly, and security determined by distraction with increasing force, till each material broke, or the knot separated completely.

Results

20% of flat reef knots (FRK) tied with all suture materials slipped; all knots tied with the other two techniques, with all materials, slipped, TK (100%) and NHCK (100%). The quantitative degree of slip, was significantly less for FRK (mean 6.3% 95%CI 2.2-10.4%) than for TK (mean 312% 95%CI 280.0-344.0%) and NHCK (mean 113.0% 95%CI 94.3-131.0%).

The mean lengths of suture in loops held within knots, tied under tension (TK mean 17.0mm 95%CI 16.3-17.7mm), and tied without appropriate hand crossing (NHCK mean 16.3mm 95%CI 15.9-16.7mm) were significantly lower than for flat reef knots (FRK mean 25.1mm 95%CI 24.2-26.0mm). The first two types of knot may have tightened more than anticipated, in comparison to flat reef knots, with potential undue tissue tension.

Conclusion

Meticulous technique of knot tying, is essential for secure knots, appropriate tissue tension, and the security of anastomoses and haemostasis effected.

Strengths and limitations

The study design was simple, with equal numbers of knots tied for each technique, and for each material.

Only a small number of participants tied knots, limiting any assessment to the effect of the knot tying technique. No inference could be drawn regarding the effect of seniority of participant.

A relatively small number of knots were tied with each of the materials limiting more detailed assessment of the effect of the suture material and size on knot security, or whether material and size had any significant influence.
Objective quantitation of EGFR protein levels using Quantitative Dot Blot (QDB) method for prognosis of gastric cancer patients
Authors: Xin Lei , Tang Fangrong , Song Bo , Yang Maozhou , Zhang Jiandi
Published: April 2021

Background

One causing factor underlying failures of several clinical trials of anti-EGFR therapies is the lack of effective method to select patients overexpressing EGFR protein. Quantitative Dot Blot method (QDB) is proposed here to measure EGFR protein levels objectively and quantitatively. Its feasibility was evaluated for prognosis of overall survival (OS) of gastric cancer patients.

Methods

Formalin Fixed Paraffin Embedded (FFPE) slices of 2×5 μm from gastric and Lung cancer specimens were used to extract total tissue lysate for QDB measurement. Absolutely quantitated EGFR protein levels were used for Kaplan-Meier Overall Survival (OS) analysis of gastric cancer patients.

Results

EGFR protein levels ranged from 0 to 772 pmole/g (n=246) for gastric, and from 0 to 2695 pmole/g (n=81) for lung cancer patients. Poor correlation was observed between quantitated EGFR levels and immunohistochemistry (IHC) scores with r=0.018, p=0.786 from Spearman’s correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric patients only through absolute quantitation, with HR at 2.29 (95%CI:1.23-4.26, p=0.0089) from multivariate cox regression OS analysis. A cutoff of 207.7 pmole/g was proposed to stratify gastric cancer patients, with 5-year survival probability at 37% for those whose EGFR levels were above the cutoff, and at 64% those below the cutoff based on Kaplan-Meier OS analysis. p=0.0057 from Log Rank test.

Conclusion

A QDB-based assay was developed for both gastric and Lung cancer specimens to measure EGFR protein levels absolutely, quantitatively and objectively. This assay should facilitate clinical trials aiming to evaluate anti-EGFR therapies retrospectively and prospectively.
A comprehensive analysis of outcomes between COVID-19 patients with an elevated serum lipase compared to those with pancreatitis
Authors: Benias Petros C , Inamdar Sumant , Wee Diana , Liu Yan , Buscaglia Jonathan M , Satapathy Sanjaya K , Trindade Arvind J ,   Northwell COVID-19 Research Consortium.
Published: April 2021

Background and Aims

COVID-19 patients may have asymptomatic hyperlipasemia without abdominal imaging findings or abdominal pain. In addition, primary and secondary pancreatitis have been described in COVID-19 patients. There is limited information on how the groups compare in outcomes. The aim is to compare outcomes among these groups.

Methods

This is a retrospective study from 12 hospitals within one healthcare system examining outcomes between hospitalized COVID-19 patients with a lipase <3x upper limit of normal (ULN), asymptomatic hyperlipasemia (>3x ULN), secondary pancreatitis (typical respiratory COVID-19 symptoms and found to have pancreatitis), and primary pancreatitis (presenting with pancreatitis).

Results

Of 11,883 patients admitted with COVID-19, 1,560 patients were included: 1,155 COVID-19 patients with a normal serum lipase (control group), 270 with an elevated lipase <3x ULN, 46 patients with asymptomatic hyperlipasemia with a lipase 3xULN, 57 patients with secondary pancreatitis, and 32 patients with primary pancreatitis. On adjusted multivariate analysis, the elevated lipase <3x ULN and asymptomatic hyperlipasemia groups had worse outcomes. The mortality was OR1.6 (95% CI 1.2-2.2) and 1.1 (95% CI 0.5-2.3), respectively. The need for mechanical ventilation was OR 2.8 (95% CI 1.2-2.1) and 2.8 (95% CI 1.5-5.2), respectively. Longer length of stay was OR 1.5 (95%CI 1.1-2.0) and 3.16 (95%CI 1.5-6.5), respectively.

Conclusion

COVID-19 patients with an elevated lipase< 3x ULN and asymptomatic hyperlipasemia have generally worse outcomes than those with pancreatitis. This could be attributed to extrapancreatic causes (liver failure, renal failure, enteritis, etc), which may signify a more severe course of clinical disease.
Ornithine Decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus
Authors: Miller Anna K , Tavera Gloria , Dominguez Ricardo L , Camargo M Constanza , Waterboer Tim , Wilson Keith T , Williams Scott M , Morgan Douglas R
Published: April 2021

The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI: 2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p = 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 × 10−3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the risk allele, C, at rs2302615.
Covid-19: Early evening curfews are not effective and may backfire
Authors: Georganas Sotiris , Velias Alina , Vandoros Sotiris
Published: April 2021

Background

During the COVID-19 pandemic, some countries have introduced early evening curfews. Several studies try measure the effectiveness of such measures across different countries, but clear identification of effects is elusive.

Objective

We examined the impact of an early evening curfew on mobility by studying a shift in curfews from 9pm to 6pm in Greece.

Data and Methods

We took advantage of a natural experiment in Greece, where curfews shifted from 9pm to 6pm in one Region, but not in another. We followed a difference-in-differences econometric approach, where we compared trends in mobility in groceries and pharmacies as well as residential spaces before and after the introduction of the 6pm curfew, in the two regions.

Results

The relative difference in the time spent in groceries and pharmacies between the two regions before and after the intervention, is statistically insignificant [coeff: −9.95; 95%CI −44.358 to 24.458]. The relative increase in time spent at residential spaces after the 6pm curfew was only 4.625 percentage points [coeff: 4.625; 95%CI 1.412 to 7.838].

Conclusions

We found that the 6pm instead of 9pm curfew in Athens led to a 4.63 percentage point relative increase in time spent at home and had no effect on time spent in groceries and pharmacies. Considering that this was a result of a 18.75% reduction in hours where people were allowed to leave home, it seems that the early evening curfew led to more crowding in indoor spaces – which may facilitate the spread of disease. Interventions should be based on a thorough analysis of human behaviour, that anticipates substitution of activities.
Do people reduce compliance with COVID-19 guidelines following vaccination? A longitudinal analysis of matched UK adults
Authors: Wright Liam , Steptoe Andrew , Mak Hei Wan , Fancourt Daisy
Published: April 2021

Introduction

COVID-19 vaccines do not confer immediate immunity and vaccinated individuals may still be at risk of transmitting the virus. Governments have not exempted vaccinated individuals from behavioural measures to reduce the spread of COVID-19, such as practicing social distancing. However, vaccinated individuals may have reduced compliance with these measures, given lower perceived risks.

Methods

We used monthly panel data from October 2020 – March 2021 in the UK COVID-19 Social Study to assess changes in compliance following vaccination. Compliance was measured with two items on compliance with guidelines in general and compliance with social distancing. We used matching to create comparable groups of individuals by month of vaccination (January, February, or not vaccinated by February) and fixed effects regression to estimate changes in compliance over the study period.

Results

Compliance increased between October 2020 – March 2021, regardless of vaccination status or month of vaccination. There was no clear evidence that vaccinated individuals decreased compliance relative to those who were not yet vaccinated.

Conclusion

There was little evidence that sample members vaccinated in January or February reduced compliance after receiving vaccination for COVID-19. Continued monitoring is required as younger individuals receive the vaccine, lockdown restrictions are lifted and individuals receive second doses of the vaccine.
Spike Protein Targeting “Nano-Glue” that Captures and Promotes SARS-CoV-2 Elimination
Authors: Zhang Guofang , Cong Yalin , Cao Guoli , Li Liang , Yu Peng , Song Qingle , Liu Ke , Qu Jing , Wang Jing , Xu Wei , Liao Shumin , Fan Yunping , Li Yufeng , Wang Guocheng , Fang Lijing , Chang Yanzhong , Zhao Yuliang , Boraschi Diana , Li Hongchang , Chen Chunying , Wang Liming , Li Yang
Published: April 2021

The global emergency caused by the SARS-CoV-2 pandemics can only be solved with adequate preventive and therapeutic strategies, both currently missing. The electropositive Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein with abundant β-sheet structure serves as target for COVID-19 therapeutic drug design. Here, we discovered that ultrathin 2D CuInP2S6(CIPS) nanosheets as a new agent against SARS-CoV-2 infection, which also able to promote viral host elimination. CIPS exhibits extremely high and selective binding capacity with the RBD of SARS-CoV-2 spike protein, with consequent inhibition of virus entry and infection in ACE2-bearing cells and human airway epithelial organoids. CIPS displays nano-viscous properties in selectively binding with spike protein (KD< 1 pM) with negligible toxicityin vitroandin vivo. Further, the CIPS-bound SARS-CoV-2 was quickly phagocytosed and eliminated by macrophages, suggesting CIPS could be successfully used to capture and facilitate the virus host elimination with possibility of triggering anti-viral immunization. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, as well as for use as disinfection agent and surface coating material to constrain the SARS-CoV-2 spreading.
Transferable representations of single-cell transcriptomic data
Authors: Weinberger Ethan , Lee Su-In
Published: April 2021

Advances in single-cell RNA-seq (scRNA-seq) technologies are enabling the construction of large-scale, human-annotated reference cell atlases, creating unprecedented opportunities to accelerate future research. However, effectively leveraging information from these atlases, such as clustering labels or cell type annotations, remains challenging due to substantial technical noise and sparsity in scRNA-seq measurements. To address this problem, we present HD-AE, a deep autoencoder designed to extract integrated low-dimensional representations of scRNA-seq measurements across datasets from different labs and experimental conditions (https://github.com/suinleelab/HD-AE). Unlike previous approaches, HD-AE’s representations successfully transfer to new query datasets without needing to retrain the model. Researchers without substantial computational resources or machine learning expertise can thus leverage the robust representations learned by pretrained HD-AE models to compare embeddings of their own data with previously generated sets of reference embeddings.
Examination of gene loss in the DNA mismatch repair pathway and its mutational consequences in a fungal phylum
Authors: Phillips Megan A , Steenwyk Jacob L , Shen Xing-Xing , Rokas Antonis
Published: April 2021

The DNA mismatch repair (MMR) pathway corrects mismatched bases produced during DNA replication and is highly conserved across the tree of life, reflecting its fundamental importance for genome integrity. Loss of function in one or a few MMR genes can lead to increased mutation rates and microsatellite instability, as seen in some human cancers. While loss of MMR genes has been documented in the context of human disease and in hypermutant strains of pathogens, examples of entire species and species lineages that have experienced substantial MMR gene loss are lacking. We examined the genomes of 1,107 species in the fungal phylum Ascomycota for the presence of 52 genes known to be involved in the MMR pathway of fungi. We found that the median ascomycete genome contained 49 / 52 MMR genes. In contrast, four closely related species of obligate plant parasites from the powdery mildew generaErysipheandBlumeria, have lost between 5 and 21 MMR genes, includingMLH3,EXO1, andDPB11. The lost genes span MMR functions, include genes that are conserved in all other ascomycetes, and loss of function of any of these genes alone has been previously linked to increased mutation rate. Consistent with the hypothesis that loss of these genes impairs MMR pathway function, we found that powdery mildew genomes with higher levels of MMR gene loss exhibit increased numbers of mononucleotide runs, longer microsatellites, accelerated sequence evolution, elevated mutational bias in the A|T direction, and decreased GC content. These results identify a striking example of macroevolutionary loss of multiple MMR pathway genes in a eukaryotic lineage, even though the mutational outcomes of these losses appear to resemble those associated with detrimental MMR dysfunction in other organisms.

Significance Statement

The DNA mismatch repair pathway corrects nucleotide base errors that occur during the replication of DNA; loss of these genes leads to cancer. We examined the conservation of the DNA mismatch repair pathway’s genes across more than 1,000 species in a fungal phylum and found a lineage of powdery mildews, a group of fungi that infect the leaves of plants, which have experienced extensive loss of multiple, otherwise highly conserved, genes. The genomes of these powdery mildews show elevated rates of diverse types of mutation, raising the hypothesis that these organisms have diversified while lacking genes thought to be essential for the accurate replication of DNA.
Selective Chemical Labeling and Sequencing of 5-Hydroxymethylcytosine in DNA at Single-Base Resolution
Authors: Li Xiaogang , Shi Xinxin , Gong Yin , Guo Wenting , Liu Yuanrui , Peng Chunwei , Xu Yingchun
Published: April 2021

5-Hydroxymethylcytosine (5hmC), the oxidative product of 5-methylcytosine (5mC) catalyzed by ten-eleven translocation (TET) enzymes, plays an important role in many biological processes as an epigenetic mediator. Prior studies have shown that 5hmC can be selectively labeled with chemically-modified glucose moieties and enriched using click chemistry with biotin affinity approaches. Besides, DNA deaminases of the AID/APOBEC family can discriminate modified 5hmC bases from cytosine (C)or 5-methylcytosine (5mC). Herein, we developed a method based on ESC whole-genome analysis which could enrich 5hmC-containing DNA by selective chemical labeling and locate 5hmC sites at single-base resolution with enzyme-based deamination. The combination experimental design is an extension of previous methods, and we hope that this cost-effective single base resolution 5hmC sequencing method could be used to promote the mechanism and diagnosis research of 5hmC.