bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Ventilation Of Two Subjects With A Single Mechanical Ventilator Using A New Medical Device: AnIn VitroStudy
Authors: Lugones Ignacio , Ramos Matías , Biancolini Fernanda , Giambastiani Roberto Orofino
Published: January 2021

INTRODUCTION

The SARS-CoV2 pandemic has created a sudden lack of ventilators. DuplicAR®is a novel device that allows simultaneous and independent ventilation of two subjects with a single ventilator. The aims of this study are: a) to determine the efficacy of DuplicAR®to independently regulate the peak and positive-end expiratory pressures in each subject, both under pressure-controlled ventilation and volume-controlled ventilation, and b) to determine the ventilation mode in which DuplicAR®presents the best performance and safety.

MATERIALS AND METHODS

Two test lungs are connected to a single ventilator using DuplicAR®. Three experimental stages are established: 1) two identical subjects, 2) two subjects with the same weight but different lung compliance, and 3) two subjects with different weight and lung compliance. In each stage, the test lungs are ventilated in two ventilation modes. The positive-end expiratory pressure requirements are increased successively in one of the subjects. The goal is to achieve a tidal volume of 7 ml/kg for each subject in all different stages through manipulation of the ventilator and the DuplicAR®controllers.

RESULTS

DuplicAR®allows adequate ventilation of two subjects with different weight and/or lung compliance and/or PEEP requirements. This is achieved by adjusting the total tidal volume for both subjects (in volume-controlled ventilation) or the highest peak pressure needed (in pressure-controlled ventilation) along with the basal positive-end expiratory pressure on the ventilator, and simultaneously manipulating the DuplicAR®controllers to decrease the tidal volume or the peak pressure in the subject that needs less and/or to increase the positive-end expiratory pressure in the subject that needs more. While ventilatory goals can be achieved in any of the ventilation modes, DuplicAR®performs better in pressure-controlled ventilation, as changes experienced in the variables of one subject do not modify the other one.

CONCLUSIONS

DuplicAR®is an effective tool to manage the peak inspiratory pressure and the positive-end expiratory pressure independently in two subjects connected to a single ventilator. The driving pressure can be adjusted to meet the requirements of subjects with different weight and lung compliance. Pressure-controlled ventilation has advantages over volume-controlled ventilation and is therefore the recommended ventilation mode.
Generalized Prediction of Hemodynamic Shock in Intensive Care Units
Authors: Nagori Aditya , Singh Pradeep , Firdos Sameena , Vats Vanshika , Gupta Arushi , Bandhey Harsh , Kalia Anushtha , Sharma Arjun , Ailavadi Prakriti , Awasthi Raghav , Bhadra Wrik , Kaul Ayushmaan , Lodha Rakesh , Sethi Tavpritesh
Published: January 2021

Early prediction of hemodynamic shock in the ICU can save lives. Several studies have leveraged a combination of vitals, lab investigations, and clinical data to construct early warning systems for shock. However, these have a limited potential of generalization to diverse settings due to reliance on non-real-time data. Monitoring data from vitals can provide an early real-time prediction of Hemodynamic shock which can precede the clinical diagnosis to guide early therapy decisions. Generalization across age and geographical context is an unaddressed challenge. In this retrospective observational study, we built real-time shock prediction models generalized across age groups (adult and pediatric), ICU-types, and geographies. We trained, validated, and tested a shock prediction model on the publicly available eICU dataset on 208 ICUs across the United States. Data from 156 hospitals passed the eligibility criteria for cohort building. These were split hospital-wise in a five-fold training-validation-test set. External validation of the model was done on a pediatric ICU in New Delhi and MIMIC-III database with more than 0.23 million and one million patient-hours vitals data, respectively. Our models identified 92% of all the shock events more than 8 hours in advance with AUROC of 86 %(SD= 1.4) and AUPRC of 93% (SD =1.2) on the eICU testing set. An AUROC of 87 % (SD =1.8), AUPRC 92 % (SD=1.6) were obtained in external validation on the MIMIC-III cohort. The New Delhi Pediatric SafeICU data achieved an AUROC of 87 % (SD =4) AUPRC 91% (SD=3), despite being completely different geography and age group. In this first, we demonstrate a generalizable model for predicting shock, and algorithms are publicly available as a pre-configured Docker environment at https://github.com/tavlab-iiitd/ShoQPred.
A Novel Abnormality Annotation Database for COVID-19 Affected Frontal Lung X-rays
Authors: Mittal Surbhi , Venugopal Vasantha Kumar , Agarwal Vikash Kumar , Malhotra Manu , Chatha Jagneet Singh , Kapur Savinay , Gupta Ankur , Batra Vikas , Majumdar Puspita , Malhotra Aakarsh , Thakral Kartik , Chhabra Saheb , Vatsa Mayank , Singh Richa , Chaudhury Santanu
Published: January 2021

Purpose

To advance the usage of CXRs as a viable solution for efficient COVID-19 diagnostics by providing large-scale annotations of the abnormalities in frontal CXRs in BIMCV-COVID19+ database, and to provide a robust evaluation mechanism to facilitate its usage.

Materials and Methods

We provide the abnormality annotations in frontal CXRs by creating bounding boxes. The frontal CXRs are a part of the existing BIMCV-COVID19+ database. We also define four different protocols for robust evaluation of semantic segmentation and classification algorithms. Finally, we benchmark the defined protocols and report the results using popular deep learning models as a part of this study.

Results

For semantic segmentation, Mask-RCNN performs the best among all the models with a DICE score of 0.43 ± 0.01. For classification, we observe that MobileNetv2 yields the best results for 2-class and 3-class classification. We also observe that deep models report a lower performance for classifying other classes apart from the COVID class.

Conclusion

By making the annotated data and protocols available to the scientific community, we aim to advance the usage of CXRs as a viable solution for efficient COVID-19 diagnostics. This large-scale data will be useful for ML algorithms and can be used for learning radiological patterns observed in COVID-19 patients. Further, the protocols will facilitate ML practitioners for unified large-scale evaluation of their algorithms.

Data Availability Statement

The data associated with this work is available here : Radiologists’ Annotations on COVID-19+ X-rays https://osf.io/b35xu/ via @OSFramework andhttp://covbase4all.igib.res.in/.
A two-phase stochastic dynamic model for COVID-19 mid-term policy recommendations in Greece: a pathway towards mass vaccination
Authors: Rachaniotis N.P. , Dasaklis T.K. , Fotopoulos F. , Tinios P.
Published: January 2021

From November 7th, 2020, Greece adopted a second nationwide lockdown policy to mitigate the transmission of SARS-CoV-2 (the first took place from March 23rdtill May 4th, 2020), just as the second wave of COVID-19 was advancing, as did other European countries. In the light of the very promising voluntary mass vaccination, which will start in January 2021, it is of utmost importance for the country to plan to complement vaccination with mid-term Non-Pharmaceutical Interventions (NPIs). The objective is to minimize human losses and to limit social and economic costs. In this paper a two-phase stochastic dynamic network compartmental model (a pre-vaccination SEIR until February 15th, 2021 and a post-vaccination SVEIR from February 15th, 2021 to June 30th, 2021) is developed. Three scenarios are assessed in the first phase: (a) abaseline scenario, which lifts the national lockdown and all NPIs on January 2021, (b) a“semi-lockdown” scenario with school opening, partial retail sector operation, universal mask wearing and social distancing/teleworking on January 2021 and (c) a “rolling lockdown” scenario combining apartial lifting of measuresin January 2021 followed by a third imposed nationwide lockdown in February 2021. In the second phase three scenarios with different vaccination rates are assessed. Publicly available data along with some preliminary first results of the SHARE COVID-19 survey conducted in Greece are used as input. The results regarding the first phase indicate that the “semi-lockdown” scenario outperforms the third lockdown scenario (5.7% less expected fatalities), whereas in the second phase it is of great importance to ensure a sufficient vaccine supply and high vaccination rates.
Timeliness of provisional United States mortality data releases during the COVID-19 pandemic: delays associated with electronic death registration system and weekly mortality
Authors: Rosenbaum Janet E. , Stillo Marco , Graves Nathaniel , Rivera Roberto
Published: January 2021

All-cause mortality counts allow public health authorities to identify populations experiencing excess deaths from pandemics, natural disasters, and other emergencies. Delays in the completeness of mortality counts may contribute to misinformation because death counts take weeks to become accurate. We estimate the timeliness of all-cause mortality releases during the Covid-19 pandemic for the dates 3 April to 5 September 2020 by estimating the number of weekly data releases of the NCHS Fluview Mortality Surveillance System until mortality comes within 99% of the counts in the 19 March 19 2021 provisional mortality data release. States’ mortality counts take 5 weeks at median (interquartile range 4--7 weeks) to completion. The fastest states were Maine, New Hampshire, Vermont, New York, Utah, Idaho, and Hawaii. States that had not adopted the electronic death registration system (EDRS) were 4.8 weeks slower to achieve complete mortality counts, and each weekly death per 10^8 was associated with a 0.8 week delay. Emergency planning should improve the timeliness of mortality data by improving state vital statistics digital infrastructure.
High prevalence of long-term psychophysical olfactory dysfunction in patients with COVID-19
Authors: Boscolo-Rizzo Paolo , Menegaldo Anna , Fabbris Cristoforo , Spinato Giacomo , Borsetto Daniele , Vaira Luigi Angelo , Calvanese Leonardo , Pettorelli Andrea , Sonego Massimo , Frezza Daniele , Bertolin Andy , Cestaro Walter , Rigoli Roberto , Tirelli Giancarlo , Mosto Maria Cristina Da , Menini Anna , Polesel Jerry , Hopkins Claire
Published: January 2021

This study prospectively assessed the long-term prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 54 (37.2) being mildly microsmic, 16 (11.0%) moderately microsmic, 7 (4.8%) severely microsmic, and 10 patients (6.9%) being anosmic. At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of sense of smell or taste and olfactory test scores (Spearman’s r=-0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of SARS-CoV-2 infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-CoV-2 infection.
Causal Mediation Analysis with Multiple Causally Ordered and Non-ordered Mediators based on Summarized Genetic Data
Authors: Hou Lei , Yu Yuanyuan , Sun Xiaoru , Liu Xinhui , Yu Yifan , Yan Ran , Li Hongkai , Xue Fuzhong
Published: January 2021

Causal mediation analysis aims to investigate the mechanism linking an exposure and an outcome. Dealing with the impact of unobserved confounders among the exposure, mediator and outcome has always been an issue of great concern. Moreover, when multiple mediators exist, this causal pathway intertwines with other causal pathways, making it more difficult to estimate of path-specific effects (PSEs). In this article, we propose a method (PSE-MR) to identify and estimate PSEs of an exposure on an outcome through multiple causally ordered and non-ordered mediators using Mendelian Randomization, when there are unmeasured confounders among the exposure, mediators and outcome. Additionally, PSE-MR can be used when pleiotropy exists, and can be implemented using only summarized genetic data. We also conducted simulations to evaluate the finite sample performances of our proposed estimators in different scenarios. The results show that the causal estimates of PSEs are almost unbiased with good coverage and Type I error properties. We illustrate the utility of our method through a study of exploring the mediation effects of lipids in the causal pathways from body mass index to cardiovascular disease.

Author summary

A new method (PSE-MR) is proposed to identify and estimate PSEs of an exposure on an outcome through multiple causally ordered and non-ordered mediators using summarized genetic data, when there are unmeasured confounders among the exposure, mediators and outcome. Lipids play important roles in the causal pathways from body mass index to cardiovascular disease
Differential encoding of safe and risky offers
Authors: Maisson David J-N. , Michael Yoo Seng Bum , Wang Maya Zhe , Cash-Padgett Tyler V. , Zimmermann Jan , Hayden Benjamin Y.
Published: January 2021

Common currency theories in neuroeconomics hold that neurons in specific brain regions specifically encode subjective values of offers and not stimulus-specific information. The rationale behind these theories is that abstract value encoding lets the decision maker compare qualitatively different options. Alternatively, expectancy-based theories hold that the brain preferentially tracks the relationship between options and their outcomes, and thus does not abstract away details of offers. To adjudicate between these theories, we examined responses of neurons in six reward regions to risky and safe offers while macaques performed a gambling task. In all regions, responses to safe options are unrelated to responses evoked by equally preferred risky options. Nor does any region appear to contain a specialized subset of value-selective neurons. Finally, in all regions, responses to risky and safe options occupy distinct response subspaces, indicating that the organizational framework for encoding risky and safe offers is different. Together, these results argue against the idea that putative reward regions carry abstract value signals, and instead support the idea that these regions carry information that links specific options to their outcomes in support of a broader cognitive map.
Multi-antigen recognition circuits overcome challenges of specificity, heterogeneity, and durability in T cell therapy for glioblastoma
Authors: Choe Joseph H. , Watchmaker Payal B. , Simic Milos S. , Gilbert Ryan D. , Li Aileen W. , Krasnow Nira A. , Carrera Diego A. , Yu Wei , Downey Kira M. , Celli Anna , Cho Juhyun , Briones Jessica D. , Dannenfelser Ruth , Cardarelli Lia , Sidhu Sachdev S. , Roybal Kole T. , Okada Hideho , Lim Wendell A.
Published: January 2021

Treatment of solid cancers with chimeric antigen receptor (CAR) T cells is plagued by the lack of target antigens that are both tumor-specific and homogeneously expressed. We show that multiantigen prime-and-kill recognition circuits have the flexibility and precision to overcome these challenges in attacking glioblastoma. A synNotch receptor that recognizes a specific priming antigen – the heterogeneous glioblastoma neoantigen EGFRvIII or a brain tissue-specific antigen – is used to locally induce expression of a CAR, enabling thorough but controlled tumor killing by targeting of homogeneous antigens that are not absolutely tumor specific. Moreover, regulated CAR expression maintains a higher fraction of the T cells in the naïve-like state which is associated with higher durabilityin vivo. In summary, using circuits that integrate recognition of multiple imperfect but complementary antigens, we improve the specificity and persistence of T cells directed against glioblastoma, providing a general recognition strategy applicable to other solid tumors.
Telomerase Prevents Emphysema in Old Mice by Sustaining Subpopulations of Endothelial and AT2 Cells
Authors: Breau Marielle , Cayrou Christelle , Churikov Dmitri , Fouillade Charles , Curras-Alonso Sandra , Bauwens Serge , Jourquin Frederic , Braud Laura , Fiore Frederic , Castellano Rémy , Josselin Emmanuelle , Sánchez-Ferrer Carlota , Giovinazzo Giovanna , Gilson Eric , Flores Ignacio , Londono-Vallejo Arturo , Adnot Serge , Géli Vincent
Published: January 2021

Accumulation of senescent cells has been causally linked to the development of age-related pathologies. Here, we characterized a new mouse model (p21+/Tert) whose telomerase (TERT) is expressed from the p21 promoter that can be activated in response to telomere dysfunction. Lung parenchyma from p21+/Tertold mice accumulated fewer senescent cells with age and this correlated with a reduction in age-related alveolar space enlargement, a feature of pulmonary emphysema. This protection against emphysema depends on TERT catalytic activity and is associated with increased proliferation of pulmonary endothelial cells (EC) and capillary density. Single-cell RNA sequencing of lung cells revealed that TERT expression was associated with the enrichment of ECs expressing genes involved in vessel regeneration and in AT2 cells overexpressing S/G2M markers. These findings indicate that p21-promoter-dependent expression of catalytically active telomerase prevents emphysema by sustaining the proliferation of subclasses of EC and AT2 cells.
Interplay between intrinsic reprogramming potential and microenvironment controls neuroblastoma cell plasticity and identity
Authors: Thirant Cécile , Peltier Agathe , Durand Simon , Kramdi Amira , Louis-Brennetot Caroline , Pierre-Eugène Cécile , Costa Ana , Grelier Amandine , Zaïdi Sakina , Gruel Nadège , Jimenez Irène , Lapouble Eve , Pierron Gaëlle , Brisse Hervé J. , Gauthier Arnaud , Fréneaux Paul , Grossetête-Lalami Sandrine , Baudrin Laura G. , Raynal Virginie , Baulande Sylvain , Bellini Angela , Bhalshankar Jaydutt , Carcaboso Angel M. , Geoerger Birgit , Rohrer Hermann , Surdez Didier , Boeva Valentina , Schleiermacher Gudrun , Delattre Olivier , Janoueix-Lerosey Isabelle
Published: January 2021

Two cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain poorly defined. Here, we demonstrate that the knock-out ofGATA3, but not ofPHOX2AorPHOX2B, in noradrenergic cells induces a mesenchymal phenotype. Our results document spontaneous plasticity in several models between both identities and show that plasticity relies on epigenetic reprogramming. We demonstrate that anin vivomicroenvironment provides a powerful pressure towards a noradrenergic identity for these models. Consistently, tumor cells with a mesenchymal identity are not detected in a series of PDX models. Further study of the intra-tumor noradrenergic heterogeneity reveals two distinct cell populations exhibiting features of chromaffin-like or sympathoblast-like cells. This work emphasizes that both external cues of the environment and intrinsic factors control plasticity and cell identity in neuroblastoma.
Creating wounds in cell monolayers using micro-jets
Authors: Soitu Cristian , Panea Mirela , Castrejón-Pita Alfonso A. , Cook Peter R. , Walsh Edmond J.
Published: January 2021

Many wound-healing assays are used in cell biology and biomedicine; they are often labor intensive and/or require specialized and costly equipment. We describe a contactless method to create wounds with any imaginable 2D pattern in cell monolayers using micro-jets of either media or an immiscible and biocompatible fluorocarbon (i.e., FC40). We also combine this with another method that allows automation and multiplexing using standard Petri dishes. A dish is filled with a thin film of media overlaid with FC40, and the two liquids reshaped into an array of microchambers in minutes. Each chamber in such a grid is isolated from others by fluid walls of FC40. Cells are now added, allowed to grow into a monolayer, and wounds created using the microjets; then, healing is monitored by microscopy. As arrays of chambers can be made using the media and Petri dishes familiar to biologists, and as dishes fit seamlessly into their incubators, microscopes, and workflows, we anticipate this assay will find wide application in biomedicine.
DeepFrag: A Deep Convolutional Neural Network for Fragment-based Lead Optimization
Authors: Green Harrison , Koes David R. , Durrant Jacob D.
Published: January 2021

1

Machine learning has been increasingly applied to the field of computer-aided drug discovery in recent years, leading to notable advances in binding-affinity prediction, virtual screening, and QSAR. Surprisingly, it is less often applied to lead optimization, the process of identifying chemical fragments that might be added to a known ligand to improve its binding affinity. We here describe a deep convolutional neural network that predicts appropriate fragments given the structure of a receptor/ligand complex. In an independent benchmark of known ligands with missing (deleted) fragments, our DeepFrag model selected the known (correct) fragment from a set over 6,500 about 58% of the time. Even when the known/correct fragment was not selected, the top fragment was often chemically similar and may well represent a valid substitution. We release our trained DeepFrag model and associated software under the terms of the Apache License, Version 2.0. A copy can be obtained free of charge fromhttp://durrantlab.com/deepfragmodel.
Invasive grass dominance over native forbs is linked to shifts in the bacterial rhizosphere microbiome
Authors: LaForgia Marina L. , Kang Hannah , Ettinger Cassandra L.
Published: January 2021

Rhizosphere microbiomes have received growing attention in recent years for their role in plant health, stress tolerance, soil nutrition, and invasion. Still, relatively little is known about how these microbial communities are altered under plant competition, and even less about whether these shifts are tied to competitive outcomes between native and invasive plants. We investigated the structure and diversity of rhizosphere bacterial and fungal microbiomes of native annual forbs and invasive annual grasses individually and in competition using high-throughput amplicon sequencing of the bacterial 16S rRNA gene and the fungal ITS region. We assessed how differentially abundant microbial families correlate to plant biomass under competition We find that bacterial diversity and structure differ between native forbs and invasive grasses, but fungal diversity and structure do not. Further, bacterial community structures under competition are distinct from individual bacterial community structures. We also identified five bacterial families that varied in normalized abundance between treatments and that were correlated with plant biomass under competition. We speculate that invasive grass dominance over these natives may be partially due to effects on the rhizosphere community, with changes in specific bacterial families potentially benefiting invaders at the expense of natives.
Using dual-calibrated functional MRI to map brain oxygen supply and consumption in multiple sclerosis
Authors: Chandler Hannah L , Stickland Rachael C , Germuska Michael , Patitucci Eleonora , Foster Catherine , Bhome-Dhaliwal Shona , Lancaster Thomas M , Saxena Neeraj , Khot Sharmila , Tomassini Valentina , Wise Richard G
Published: January 2021

Evidence suggests that cerebrovascular function and oxygen consumption are altered in multiple sclerosis (MS). Here, we quantified the vascular and oxygen metabolic MRI burden in patients with MS (PwMS) and assessed the relationship between these MRI measures of and metrics of damage and disability. In PwMS and in matched healthy volunteers, we applied a newly developed dual-calibrated fMRI method of acquisition and analysis to map grey matter (GM) cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen consumption (CMRO2) and effective oxygen diffusivity of the capillary network (DC). We also quantified physical and cognitive function in PwMS and controls. There was no significant difference in GM volume between 22 PwMS and 20 healthy controls (p=0.302). Significant differences in CBF (PwMS vs. controls: 44.91 ± 6.10 vs. 48.90 ± 5.87 ml/100g/min,p=0.010), CMRO2(117.69 ± 17.31 vs. 136.49 ± 14.48 μmol/100g/minp<0.001) and DC(2.70 ± 0.51 vs. 3.18 ± 0.41 μmol/100g/mmHg/min,p=0.002) were observed in the PwMS. No significant between-group differences were observed for OEF (PwMS vs. controls: 0.38 ± 0.09 vs. 0.39 ± 0.02,p=0.358). Regional analysis showed widespread reductions in CMRO2and DCfor PwMS compared to healthy volunteers. There was a significant correlation between physiological measures and T2 lesion volume, but no association with current clinical disability. Our findings demonstrate concurrent reductions in oxygen supply and consumption in the absence of an alteration in oxygen extraction that may be indicative of a reduced demand for oxygen (O2), an impaired transfer of O2from capillaries to mitochondria, and/or a reduced ability to utilise O2that is available at the mitochondria. With no between-group differences in GM volume, our results suggest that changes in brain physiology may precede MRI-detectable GM loss and thus may be one of the pathological drivers of neurodegeneration and disease progression.
Transcriptomics provides a genetic signature of vineyard site with insight into vintage-independent regional wine characteristics
Authors: Reiter Taylor , Montpetit Rachel , Byer Shelby , Frias Isadora , Leon Esmeralda , Viano Robert , Mcloughlin Michael , Halligan Thomas , Hernandez Desmon , Figueroa-Balderas Rosa , Cantu Dario , Steenwerth Kerri , Runnebaum Ron , Montpetit Ben
Published: January 2021

In wine fermentations, the metabolic activity of bothSaccharomyces cerevisiaeand non-Saccharomycesorganisms impact wine chemistry. Ribosomal DNA amplicon sequencing of grape musts has demonstrated that microorganisms occur non-randomly and are associated with the vineyard of origin, suggesting a role for the vineyard, grape, and wine microbiome in shaping wine fermentation outcomes. We used ribosomal DNA amplicon sequencing of grape must and RNA sequencing of primary fermentations to profile fermentations from 15 vineyards in California and Oregon across two vintages. We find that the relative abundance of fungal organisms detected by ribosomal DNA amplicon sequencing did not correlate with transcript abundance from those organisms within the RNA sequencing data, suggesting that the majority of the fungi detected in must by ribosomal DNA amplicon sequencing are not active during these inoculated fermentations. Additionally, we detect genetic signatures of vineyard site and region during fermentation that are predictive for each vineyard site, identifying nitrogen, sulfur, and thiamine metabolism as important factors for distinguishing vineyard site and region.

Importance

The wine industry generates billions of dollars of revenue annually, and economic productivity is in part associated with regional distinctiveness of wine sensory attributes. Microorganisms associated with grapes and wineries are influenced by region of origin, and given that some microorganisms play a role in fermentation, it is thought that microbes may contribute to the regional distinctiveness of wine. We show that while the presence of microbial DNA is associated with wine region and vineyard site, the presence of microbial DNA is not associated with gene expression of those microorganisms during fermentation. We further show that detected gene expression signatures associated with wine region and vineyard site provide a means to address differences in fermentations that may drive regional distinctiveness.
MassMark: A Highly Scalable Multiplex NGS-based Method for High-Throughput, Accurate and Sensitive Detection of SARS-CoV-2 for Mass Testing
Authors: Ngeow Kao Chin , Xie Chao , Teo Alvin Kuo Jing , Hsu Li Yang , Tan Min Han , Choudhury Yukti
Published: January 2021

Mass testing has been proposed as a strategy to address and contain the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic1,2. We have developed MassMark, a novel and highly scalable multiplex method that employs next generation sequencing for high-throughput, accurate and sensitive detection of SARS-CoV-2, while minimizing handling complexity and resources by utilizing a serial pooling strategy to accommodate over 9,000 samples per workflow. Analytical validation showed that MassMark was able to detect SARS-CoV-2 RNA down to a level of 100 copies per reaction. We evaluated the clinical performance of MassMark in a simulated screening testing with 22 characterized samples from three different sources (nasopharyngeal swabs, nasal swabs and saliva), comprising of 12 SARS-CoV-2 positive samples with mid to late Ct values (range: 22.98-32.72) and 10 negative samples. There was one false negative and no false positives, giving an overall sensitivity and specificity of 91.67% and 100% respectively, when compared against an optimized RT-PCR test with a target size within 70 bp (CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel3).
BinomiRare: A carriers-only test for association of rare genetic variants with a binary outcome for mixed models and any case-control proportion
Authors: Sofer Tamar , Lee Jiwon , Kurniansyah Nuzulul , Jain Deepti , Laurie Cecelia A. , Gogarten Stephanie M. , Conomos Matthew P. , Heavner Ben , Hu Yao , Kooperberg Charles , Haessler Jeffrey , Vasan Ramachandran S. , Cupples L. Adrienne , Coombes Brandon J. , Seyerle Amanda , Gharib Sina A. , Chen Han , O’Connell Jeffrey R. , Zhang Man , Gottlieb Daniel , Psaty Bruce M. , Longstreth W.T. , Rotter Jerome I. , Taylor Kent D. , Rich Stephen S. , Guo Xiuqing , Boerwinkle Eric , Morrison Alanna C. , Pankow James S. , Johnson Andrew D. , Pankratz Nathan ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Reiner Alex P. , Redline Susan , Smith Nicholas L. , Rice Kenneth M. , Schifano Elizabeth D.
Published: January 2021

Whole genome and exome sequencing studies have become increasingly available and are being used to identify rare genetic variants associated with health and disease outcomes. Investigators routinely use mixed models to account for genetic relatedness or other clustering variables (e.g. family or household) when testing genetic associations. However, no existing tests of the association of a rare variant association with a binary outcome in the presence of correlated data controls the Type 1 error where there are (1) few carriers of the rare allele, (2) a small proportion of cases relative to controls, and (3) covariates to adjust for. Here, we address all three issues in developing the carriers-only test framework for testing rare variant association with a binary trait. In this framework, we estimate outcome probabilities under the null hypothesis, and then use them, within the carriers, to test variant associations. We extend the BinomiRare test, which was previously proposed for independent observations, and develop the Conway-Maxwell-Poisson (CMP) test, and study their properties in simulations. We show that the BinomiRare test always controls the type 1 error, while the CMP test sometimes does not. We then use the BinomiRare test to test the association of rare genetic variants in target genes with small vessel disease stroke, short sleep, and venous thromboembolism, in whole-genome sequence data from the Trans-Omics for Precision Medicine program.
Mathematical Model of a Personalized Neoantigen Cancer Vaccine and the Human Immune System: Evaluation of Efficacy
Authors: Messan Marisabel Rodriguez , Yogurtcu Osman N. , McGill Joseph R. , Nukala Ujwani , Sauna Zuben E. , Yang Hong
Published: January 2021

Cancer vaccines are an important component of the cancer immunotherapy toolkit enhancing immune response to malignant cells by activating CD4+ and CD8+ T cells. Multiple successful clinical applications of cancer vaccines have shown good safety and efficacy. Despite the notable progress, significant challenges remain in obtaining consistent immune responses across heterogeneous patient populations, as well as various cancers. We present as a proof of concept a mechanistic mathematical model describing key interactions of a personalized neoantigen cancer vaccine with an individual patient’s immune system. Specifically, the model considers the vaccine concentration of tumor-specific antigen peptides and adjuvant, the patient’s major histocompatibility complexes I and II copy numbers, tumor size, T cells, and antigen presenting cells. We parametrized the model using patient-specific data from a recent clinical study in which individualized cancer vaccines were used to treat six melanoma patients. Model simulations predicted both immune responses, represented by T cell counts, to the vaccine as well as clinical outcome (determined as change of tumor size). These kinds of models have the potential to lay the foundation for generating in silico clinical trial data and aid the development and efficacy assessment of personalized cancer vaccines.

Author summary

Personalized cancer vaccines have gained attention in recent years due to the advances in sequencing techniques that have facilitated the identification of multiple tumor-specific mutations. This type of individualized immunotherapy has the potential to be specific, efficacious, and safe since it induces an immune response to protein targets not found on normal cells. This work focuses on understanding and analyzing important mechanisms involved in the activity of personalized cancer vaccines using a mechanistic mathematical model. This model describes the interactions of a personalized neoantigen peptide cancer vaccine, the human immune system and tumor cells operating at the molecular and cellular level. The molecular level captures the processing and presentation of neoantigens by dendritic cells to the T cells using cell surface proteins. The cellular level describes the differentiation of dendritic cells due to peptides and adjuvant concentrations in the vaccine, activation, and proliferation of T cells in response to treatment, and tumor growth. The model captures immune response behavior to a vaccine associated with patient specific factors (e.g., different initial tumor burdens). Our model serves as a proof of concept displaying its utility in clinical outcomes prediction, lays foundation for developing in silico clinical trials, and aids in the efficacy assessment of personalized vaccines.
An Augmented SEIR Model with Protective and Hospital Quarantine Dynamics for the Control of COVID-19 Spread
Authors: Rohith G.
Published: January 2021

In this work, an attempt is made to analyse the dynamics of COVID-19 outbreak mathematically using a modified SEIR model with additional compartments and a nonlinear incidence rate with the help of bifurcation theory. Existence of a forward bifurcation point is presented by deriving conditions in terms of parameters for the existence of disease free and endemic equilibrium points. The significance of having two additional compartments, viz., protective and hospital quarantine compartments, is then illustrated via numerical simulations. From the analysis and results, it is observed that, by properly selecting transfer functions to place exposed and infected individuals in protective and hospital quarantine compartments, respectively, and with apt governmental action, it is possible to contain the COVID-19 spread effectively. Finally, the capability of the proposed model in predicting/representing the COVID-19 dynamics is presented by comparing with real-time data.
Women in Health Care Experiencing Occupational Stress and Burnout during COVID-19: A Review
Authors: Sriharan Abi , Ratnapalan Savithiri , Tricco Andrea C. , Lupea Doina
Published: January 2021

Context

COVID-19 has had an unprecedent impact on physicians, nurses, and other health professionals around the world, and a serious health care burnout crisis is emerging as a result of this pandemic.

Objectives

We aim to identify the causes of occupational stress and burnout in women in medicine, nursing, and other health professions during the COVID-19 pandemic and interventions that can support female health professionals deal with this crisis through a rapid review.

Methods

We searched MEDLINE, Embase, CINAHL, PsycINFO, and ERIC from December 2019 through September 30, 2020. The review protocol was registered in PROSPERO and is available online. We selected all empirical studies that discussed stress and burnout in women health care workers during the COVID-19 pandemic.

Results

The literature search identified 6148 citations. A review of abstracts led to the retrieval of 721 full-text articles for assessment, of which 47 articles were included for review. Our findings show that concerns of safety (65%), staff and resource adequacy (43%), workload and compensation (37%), job roles and security (41%) appeared as common triggers of stress in the literature.

Conclusions and Relevance

The current literature primarily focuses on self-focused initiatives such as wellness activities, coping strategies, reliance of family, friends and work colleagues to organizational led initiatives such as access to psychological support and training. Very limited evidence exists about the organizational interventions such as work modification, financial security, and systems improvement.
Pathways and signatures of mutagenesis at targeted DNA nicks
Authors: Zhang Yinbo , Davis Luther , Maizels Nancy
Published: January 2021

Nicks are the most frequent form of DNA damage and a potential source of mutagenesis in human cells. By deep sequencing, we have identified factors and pathways that promote and limit mutagenic repair at targeted nicks. BRCA2 inhibits all categories of mutational events at nicks, including indels, SNVs and HDR. DNA2 and RPA promote 5’ resection. Most insertions at nicks consist of a single C incorporated opposite the nick by the translesion polymerase REV1. DNA2 and REV3 inhibit these 1 bp insertions; and DNA2 also inhibits 1 bp deletions. Longer deletions are stimulated by DNA2, REV7 and POLQ. Strikingly, POLQ generates most SNVs at both nicks and double-strand breaks. These results identify mutagenic signatures of DNA2, REV1, REV3, REV7 and POLQ at nicks and highlight the potential for nicks to promote mutagenesis, especially in BRCA-deficient cells.
Gut microbiota ofDrosophila subobscuracontributes to its heat tolerance but is sensitive to transient thermal stress
Authors: Jaramillo Angélica , Castañeda Luis E.
Published: January 2021

Global warming impacts the animal’s fitness, leading to increasing extinction risk in ectotherm species. Gut microbiota can contribute to host physiology leading to an increase of resistance to abiotic stress conditions. Temperature has profound effects on ectotherms and gut microbiota can influence cold and heat tolerance of ectotherm species. Additionally, the gut microbiota is sensitive to environmental temperature, which induces changes in its composition and diversity. Here, we investigated the role of the gut microbiota on heat tolerance ofDrosophila subobscura, comparing the knockdown time between conventional and axenic, and we also assessed the impact of heat stress on the diversity and community structure of the gut microbiota, comparing non-stressed and heat-stressed flies. Our findings provide evidence that gut microbiota influences heat tolerance, and that heat stress modifies the gut microbiota at taxonomical and structural levels. These results demonstrate that gut microbiota contributes to heat tolerance but it is also highly sensitive to transient heat stress, which could have important effects on host fitness, population risk extinction, and vulnerability of ectotherms to current and future climatic conditions.
FLAgellum Member 8 modulates extravascular trypanosome distribution in the mammalian host
Authors: Alvarez Estefanía Calvo , Travaillé Christelle , Crouzols Aline , Rotureau Brice
Published: January 2021

The African trypanosome flagellum is an essential organelle in multiple aspects of the parasites’ development. Here, we investigated the role of a flagellar protein termed FLAgellar Member 8 (FLAM8) that is specifically distributed along the entire flagellum in trypanosomes stages of the vertebrate host. Analyses of knockdown and knockout trypanosomes demonstrated that FLAM8 is not essentialin vitrofor survival, growth, motility and slender to stumpy differentiation. Functional investigations in experimental infections showed thatFLAM8-deprived trypanosomes are able to establish and maintain the infection in the blood circulation, and to differentiate into insect transmissible forms. However, quantitative bioluminescence imaging revealed thatFLAM8-null parasites exhibit an impaired dissemination in the extravascular compartment, that is partially restored by the addition of a single rescue copy ofFLAM8. Interestingly, among all dissected organs scrutinized individually, only the skin of mice infected withFLAM8-deprived parasites showed a significant reduction in extravascular trypanosome population as compared to mice infected with parental controls. To our knowledge, FLAM8 is the first example of a flagellar protein that modulatesT. bruceiparasite distribution in the host tissues, contributing to the maintenance of extravascular parasite populations in mammalian anatomical niches, especially in the skin.

Take away

FLAM8 is dispensablein vitrofor survival, growth, motility and differentiation ofT. brucei.

FLAM8 depletion does not affect parasitemia and bloodstream form differentiationin vivo.

FLAM8 modulates the extravascular dissemination of trypanosomes in the mammalian host, especially in the skin.
Towards the restoration of ancient hominid craniofacial anatomy: Chimpanzee morphology reveals covariation between craniometrics and facial soft tissue thickness
Authors: Campbell Ryan M , Vinas Gabriel , Henneberg Maciej
Published: January 2021

In modern humans, facial soft tissue thicknesses have been shown to covary with craniometric dimensions. However, to date it has not been confirmed whether these relationships are shared with non-human apes. In this study, we analyze these relationships in chimpanzees (Pan troglodytes) with the aim of producing regression models for approximating facial soft tissue thicknesses in Plio-Pleistocene hominid individuals. Using CT scans of 19 subjects, 637 soft tissue, and 349 craniometric measurements, statistically significant multiple regression models were established for 26 points on the face and head. Examination of regression model validity resulted in minimal differences between observed and predicted soft tissue thickness values. Assessment of interspecies compatibility using a bonobo (Pan paniscus) and modern human(Homo sapiens) subject resulted in minimal differences for the bonobo but large differences for the modern human. These results clearly show that (1) soft tissue thicknesses covary with craniometric dimensions inP. troglodytes, (2) confirms that such covariation is uniformly present in both extantHomoandPanspecies, and (3) suggests that chimp-derived regression models have interspecies compatibility with hominids who have similar craniometric dimensions toP. troglodytes. As the craniometric dimensions of early hominids, such as South African australopithecines, are more similar toP. troglodytesthan those ofH. sapiens, chimpanzee-derived regression models may be used for approximating their craniofacial anatomy. It is hoped that the results of the present study and the reference dataset for facial soft tissue thicknesses of chimpanzees it provides will encourage further research into this topic.
Auto-CORPus: A Natural Language Processing Tool for Standardising and Reusing Biomedical Literature
Authors: Beck Tim , Shorter Tom , Hu Yan , Li Zhuoyu , Sun Shujian , Popovici Casiana M. , McQuibban Nicholas A. R. , Makraduli Filip , Yeung Cheng S. , Rowlands Thomas , Posma Joram M.
Published: January 2021

To analyse large corpora using machine learning and other Natural Language Processing (NLP) algorithms, the corpora need to be standardised. The BioC format is a community-driven simple data structure for sharing text and annotations, however there is limited access to biomedical literature in BioC format and a lack of bioinformatics tools to convert online publication HTML formats to BioC. We present Auto-CORPus (Automated pipeline for Consistent Outputs from Research Publications), a novel NLP tool for the standardisation and conversion of publication HTML and table image files to three convenient machine-interpretable outputs to support biomedical text analytics. Firstly, Auto-CORPus can be configured to convert HTML from various publication sources to BioC. To standardise the description of heterogenous publication sections, the Information Artifact Ontology is used to annotate each section within the BioC output. Secondly, Auto-CORPus transforms publication tables to a JSON format to store, exchange and annotate table data between text analytics systems. The BioC specification does not include a data structure for representing publication table data, so we present a JSON format for sharing table content and metadata. Inline tables within full-text HTML files and linked tables within separate HTML files are processed and converted to machine-interpretable table JSON format. Finally, Auto-CORPus extracts abbreviations declared within publication text and provides an abbreviations JSON output that relates an abbreviation with the full definition. This abbreviation collection supports text mining tasks such as named entity recognition by including abbreviations unique to individual publications that are not contained within standard bio-ontologies and dictionaries.

Availability

The Auto-CORPus package is freely available with detailed instructions from Github athttps://github.com/omicsNLP/Auto-CORPus/.