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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 128,741 papers from 551,614 authors.

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101081: Identification of evolutionarily conserved nuclear matrix proteins and their prokaryotic origins
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Posted 04 Dec 2019

Identification of evolutionarily conserved nuclear matrix proteins and their prokaryotic origins
202 downloads bioRxiv molecular biology

Rahul Sureka, Rakesh K Mishra

Compared to prokaryotic cells, a typical eukaryotic cell is much more complex along with its endomembrane system and membrane-bound organelles. Although the endosymbiosis theories convincingly explain the evolution of membrane-bound organelles such as mitochondria and chloroplasts, very little is understood about the evolutionary origins of the nucleus, the defining feature of eukaryotes. Most studies on nuclear evolution have not been able to take into consideration the underlying structural framework of the nucleus, attributed to the nuclear matrix (NuMat), a ribonucleoproteinaceous structure. This can largely be attributed to the lack of annotation of its core components. Since, NuMat has been shown to provide a structural platform for facilitating a variety of nuclear functions such as replication, transcription, and splicing, it is important to identify its protein components to better understand these processes. In this study, we address this issue using the developing embryos of D. melanogaster and D. rerio and identify 362 core NuMat proteins that are conserved between the two organisms. We find that of them, 132 protein groups have originated from pre-existing proteins in prokaryotes. While 51 were conserved across all eukaryotic supergroups, 17 new proteins evolved before the evolution of the last eukaryotic common ancestor and together these 68 proteins out of the 362 core conserved NuMat proteins are conserved across all eukaryotes indicating their indispensable nature for nuclear function for over 1.5 billion years of eukaryotic history. Our analysis paves the way to understand the evolution of the complex internal nuclear architecture and its functions.

101082: Mixture distributions in a stochastic gene expression model with delayed feedback
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Posted 26 Nov 2019

Mixture distributions in a stochastic gene expression model with delayed feedback
202 downloads bioRxiv systems biology

Pavol Bokes, Alessandro Borri, Pasquale Palumbo, Abhyudai Singh

Noise in gene expression can be substantively affected by the presence of production delay. Here we consider a mathematical model with bursty production of protein, a one-step production delay (the passage of which activates the protein), and feedback in the frequency of bursts. We specifically focus on examining the steady-state behaviour of the model in the slow-activation (i.e. large-delay) regime. Using a quasi-steady-state (QSS) approximation, we derive an autonomous ordinary differential equation for the inactive protein that applies in the slow-activation regime. If the differential equation is monostable, the steady-state distribution of the inactive (active) protein is approximated by a single Gaussian (Poisson) mode located at the globally stable steady state of the differential equation. If the differential equation is bistable (due to cooperative positive feedback), the steady-state distribution of the inactive (active) protein is approximated by a mixture of Gaussian (Poisson) modes located at the stable steady states; the weights of the modes are determined from a WKB approximation to the stationary distribution. The asymptotic results are compared to numerical solutions of the chemical master equation.

101083: Structural and functional insights into the mechanism of action of plant boron transporters
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Posted 16 Dec 2020

Structural and functional insights into the mechanism of action of plant boron transporters
202 downloads bioRxiv plant biology

Savvas Saouros, Thotegowdanapalya C. Mohan, Cristina Cecchetti, Silke Lehmann, Joseph D. Barritt, Nicola J. Scull, Paul Simpson, Yilmaz Alguel, Alexander D. Cameron, Alexandra M. E. Jones, Bernadette Byrne

Boron has essential roles in plant growth and development. BOR proteins are key in the active uptake and distribution of boron, and regulation of intracellular boron concentrations. However, their mechanism of action remains poorly studied. BOR proteins are members of the SLC4 family of transporters and thus homologues of well studied mammalian transporters including the human Anion Exchanger 1 (hAE1). Here we generated Arabidopsis thaliana BOR1 (AtBOR1) variants based i) on known disease causing mutations of hAE1 (S466R, A500R) and ii) a loss of function mutation (D311A) identified in the yeast BOR protein, ScBOR1p. The AtBOR1 variants express in yeast and localise to the plasma membrane, although both S466R and A500R exhibit lower expression than the WT AtBOR1 and D311A. The D311A, S466R and A500R mutations result in a loss of boron efflux activity in a yeast bor1p knockout strain. A. thaliana plants containing these three individual mutations exhibit substantially decreased growth phenotypes in soil under conditions of low boron. These data confirm an important role for D311 in the function of the protein and show that mutations equivalent to disease causing mutations in hAE1 have major effects in AtBOR1. We also obtained a low resolution cryo-EM structure of a BOR protein from Oryza sativa, OsBOR3 lacking the 30 C-terminal amino acids. This structure confirms the gate and core domain organisation previously observed for related proteins, and is strongly suggestive of an inward facing conformation.

101084: Diagnosis of SARS-Cov-2 infection using specimens other than naso- and oropharyngeal swabs: a systematic review and meta-analysis
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Posted 20 Jan 2021

Diagnosis of SARS-Cov-2 infection using specimens other than naso- and oropharyngeal swabs: a systematic review and meta-analysis
202 downloads medRxiv infectious diseases

Vania M. Moreira, Paulo Mascarenhas, Vanessa Machado, Joao Botelho, Jose Joao Mendes, Nuno Taveira, Maria Gabriela Almeida

Background The rapid and accurate testing of SARS-CoV-2 infection is still crucial to mitigate, and eventually halt, the spread of this disease. Currently, nasopharyngeal swab (NPS) and oropharyngeal swab (OPS) are the recommended standard sampling, yet, with some limitations. Several specimens that are easier to collect are being tested as alternatives to nasal/throat swabs in nucleic acid assays for SARS-CoV-2 detection. This study aims to critically appraise and compare the clinical performance of RT-PCR tests using oral saliva, deep-throat saliva/ posterior oropharyngeal saliva (DTS/POS), sputum, urine, feces, and tears/conjunctival swab [CS]) against standard specimens (NPS, OPS, or a combination of both). Methods In this systematic review and meta-analysis, five databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) were searched up to the 30th of December 2020. Case-control and cohort studies on the detection of SARS-CoV-2 were included. Methodological quality was assessed through the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2). Findings We identified 3022 entries, 33 of which (1.1%) met all required criteria and were included for the quantitative data analysis. Saliva presented the higher accuracy, 92.1% (95% CI: 70.0-98.3), with an estimated sensitivity of 83.9% (95% CI: 77.4-88.8) and specificity of 96.4% (95% CI: 89.5-98.8). DTS/POS samples had an overall accuracy of 79.7% (95% CI: 43.3-95.3), with an estimated sensitivity of 90.1% (95% CI: 83.3-96.9) and specificity of 63.1% (95% CI: 36.8-89.3). Remaining index specimens presented uncertainty given the lack of studies available. Interpretation Our meta-analysis shows that saliva samples from oral region provide a high sensitivity and specificity, being the best candidate as an alternative specimen to NPS/OPS for COVID-19 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial since DTS/POS samples may induce a higher rate of false positives. Urine, feces, tears/CS and sputum seem unreliable for diagnosis. Saliva testing may increase testing capacity, ultimately promoting the implementation of truly deployable COVID-19 tests, which could either work at the point-of-care (e.g. hospitals, clinics) or outbreak control spots (e.g. schools, airports, and nursing homes). Funding Nothing to declare.

101085: Estimating the global reduction in transmission and rise in detection capacity of the novel coronavirus SARS-CoV-2 in early 2020
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Posted 11 Sep 2020

Estimating the global reduction in transmission and rise in detection capacity of the novel coronavirus SARS-CoV-2 in early 2020
202 downloads medRxiv epidemiology

Antoine Belloir, Francois Blanquart

To better control the SARS-CoV-2 pandemic, it is essential to quantify the impact of control measures and the fraction of infected individuals that are detected. To this end we developed a deterministic transmission model based on the renewal equation and fitted the model to daily case and death data in the first few months of 2020 in 79 countries and states, representing 4.2 billions individuals. Based on a region-specific infection fatality ratio, we inferred the time-varying probability of case detection and the time-varying decline in transmissiblity. As a validation, the predicted total number of infected was close to that found in serosurveys; more importantly, the inferred probability of detection strongly correlated with the number of daily tests per inhabitant, with 50% detection achieved with 0.003 daily tests per inhabitants. Most of the decline in transmission was explained by the reductions in transmissibility (social distancing), which avoided 10 millions deaths in the regions studied over the first four months of 2020. In contrast, symptom-based testing and isolation of positive cases was not an efficient way to control the spread of the disease, as a large part of transmission happens before symptoms and only a small fraction of infected individuals was typically detected. The latter is explained by the limited number of tests available, and the fact that increasing test capacity increases the probability of detection less than proportionally. Together these results suggest that little control can be achieved by symptom-based testing and isolation alone.

101086: A duplicated copy of the meiotic gene ZIP4 preserves up to 50% pollen viability and grain number in polyploid wheat
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Posted 22 Jan 2021

A duplicated copy of the meiotic gene ZIP4 preserves up to 50% pollen viability and grain number in polyploid wheat
202 downloads bioRxiv plant biology

Abdul Kader Alabdullah, Graham Moore, Azahara C. Martin

Although most flowering plants are polyploid, little is known of how the meiotic process evolved to stabilise and preserve polyploid fertility. On wheat polyploidisation, the major meiotic gene ZIP4 on chromosome 3B duplicated onto 5B and subsequently diverged. This 5B meiotic gene copy (TaZIP4-B2) was recently shown to promote homologous pairing, synapsis and crossover, and suppress homoeologous crossover. We therefore suspected that these stabilising effects on meiosis could be important for the preservation of wheat polyploid fertility. A CRISPR Tazip4-B2 mutant was exploited to assess the contribution of the 5B duplicated ZIP4 copy in maintaining pollen viability and grain setting. Analysis demonstrated abnormalities in 56% of meiocytes in the Tazip4-B2 mutant, with micronuclei in 50% of tetrads, reduced size in 48% of pollen grains and a near 50% reduction in grain number. Further studies showed that most of the reduced grain number resulted from pollination with less viable pollen, suggesting that the stabilising effect of TaZIP4-B2 on meiosis has a greater consequence in subsequent male, rather than female gametogenesis. These studies reveal the extraordinary value of the wheat chromosome 5B TaZIP4-B2 duplication to agriculture and human nutrition. Future studies should assess whether different TaZIP4-B2 alleles exhibit variable effects on meiotic stabilisation and/or resistance to temperature change.

101087: The Uncertain COVID-19 Spread Pattern in India: A Statistical Analysis of the Current Situation
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Posted 02 Sep 2020

The Uncertain COVID-19 Spread Pattern in India: A Statistical Analysis of the Current Situation
202 downloads medRxiv epidemiology

Hemanta K. Baruah

There are standard techniques of forecasting the spread of pandemics. Uncertainty however is always associated with such forecasts. In this article, we are going to discuss the uncertain situation currently prevailing in the COVID-19 spread in India. For statistical analysis, we have considered the total number of cases for 60 consecutive days, from June 23 to August 21. We have seen that instead of taking data of all 60 days together, a better picture of uncertainty can be observed if we consider the data separately in three equal parts from June 23 to July 12, from July 13 to August 1, and from August 2 to August 21. For that we would first need to ascertain that the current spread pattern in India is almost exponential. Thereafter we shall show that the data regarding the total number of cases in India are not really behaving in an expected way, making forecasting the time to peak very difficult. We have found that the pandemic would perhaps change its pattern of growth from nearly exponential to nearly logarithmic, which we have earlier observed in the case of Italy, in less than 78 days starting from August 2. AMS Mathematics Subject Classification (2010)97K70

101088: Functional strain redundancy and persistent phage infection in Swiss hard cheese starter cultures
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Posted 14 Jan 2021

Functional strain redundancy and persistent phage infection in Swiss hard cheese starter cultures
202 downloads bioRxiv microbiology

Vincent Somerville, H&eacutel&egravene Berthoud, Remo S. Schmid, Hans-Peter Bachmann, H&eacutel&egravene Yi Meng, Pascal Fuchsmann, Ueli von Ah, Philipp Engel

Undefined starter cultures are poorly characterized bacterial communities from environmental origin used in cheese making. They are phenotypically stable and propagated under constant conditions in milk. This makes them interesting for understanding eco-evolutionary dynamics governing microbial communities. While cheese starter cultures are known to be dominated by a few bacterial species, little is known about the composition, functional relevance, and temporal dynamics of strain-level diversity. Here, we applied shotgun metagenomics to an important Swiss cheese starter culture and analyzed historical and experimental samples reflecting overall 82 years of starter culture propagation. We found that the bacterial community is highly stable and dominated by only a few coexisting strains of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. lactis. Genome sequencing, metabolomics analysis, and co-culturing experiments show that these strains are functionally redundant, but differ tremendously in their phage resistance potential. Moreover, we identified two highly abundant Streptococcus phages that seem to stably coexist in the community without any negative impact on bacterial growth or strain persistence, and despite the presence of a large and diverse repertoire of matching CRISPR spacers. Our findings show that functionally equivalent strains can coexist in domesticated microbial communities and highlight an important role of bacteria-phage interactions that are different from kill-the-winner dynamics.

101089: Validation of self-collected buccal swab and saliva as a diagnostic tool for COVID-19
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Posted 05 Oct 2020

Validation of self-collected buccal swab and saliva as a diagnostic tool for COVID-19
202 downloads medRxiv infectious diseases

Chee Wai Ku, Durai Shivani, Jacqueline Q T Kwan, See Ling Loy, Christina Erwin, Karrie K K Ko, Xiang Wen Ng, Lynette Oon, Koh Cheng Thoon, Shirin Kalimuddin, Jerry K.Y. Chan

BackgroundEffective management of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) requires large-scale testing. Collection of nasopharyngeal swab (NPS) by healthcare workers (HCW) is currently used to diagnose SARS-CoV-2, which increases the risk of transmission to HCWs. Self-administered saliva and buccal swabs are convenient, painless and safe alternative sample collection methods. MethodsA cross-sectional single centre study was conducted on 42 participants who were tested positive for SARS-CoV-2 via NPS within the past 7 days. A self-collected saliva and buccal swab and a HCW-collected NPS were obtained. Real-time polymerase chain reaction (RT-PCR) was performed and cycle threshold (CT) values were obtained. Positive percent agreement (PPA), negative percent agreement (NPA) and overall agreement (OA) were calculated for saliva and buccal swabs, as compared with NPS. ResultsAmong the 42 participants, 73.8% (31/42) tested positive via any one of the 3 tests. With reference to NPS, the saliva test had PPA 66.7%, NPA 91.7% and OA 69.0%. The buccal swab had PPA 56.7%, NPA 100% and OA 73.8%. Presence of symptoms improved diagnostic accuracy. There was no statistically significant association between CT values and duration of symptom onset within the first 12 days of symptoms for all three modalities. ConclusionSelf-collected saliva tests and buccal swabs have only moderate agreement with HCW-collected NPS swabs. Primary screening for SARS-CoV-2 may be performed with a saliva test or buccal swab, with a negative test warranting a confirmatory NPS to avoid false negatives. This combined strategy minimizes discomfort and reduces the risk of spread to the community and HCWs.

101090: STUDY PROTOCOL: Relationship between In-person Instruction and COVID-19 incidence among University Students: A Prospective Cohort Study
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Posted 02 Sep 2020

STUDY PROTOCOL: Relationship between In-person Instruction and COVID-19 incidence among University Students: A Prospective Cohort Study
202 downloads medRxiv public and global health

Atle Fretheim, Martin Flato, Arnfinn Helleve, Solvi Helseth, Gro Jamtvedt, Borghild Loyland, Ida Hellum Sandbekken, Alexander Schjoll, Kjetil Elias Telle, Sara Sofie Viksmoen Watle

Whether university teaching on campus with infection control measures in place is associated with higher risk of COVID-19 than online instruction, is unknown. We will assess this by conducting repeated surveys among students at universities and university colleges in Norway, where some instruction is given in-person, and some is provided online (hybrid model). We will ask about the students COVID-19 status, and how much in-person and online instruction they are getting. We will estimate the association between in-person instruction and COVID-19-risk using multivariate regression, controlling for likely confounders. We will also assess whether type of instruction is associated with how satisfied the students are with the instruction, their quality of life, and learning outcomes.

101091: Early detection of SARS-CoV-2 infection cases or outbreaks at nursing homes by targeted wastewater tracking
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Posted 22 Jan 2021

Early detection of SARS-CoV-2 infection cases or outbreaks at nursing homes by targeted wastewater tracking
202 downloads medRxiv infectious diseases

Laura Davo, Raimundo Segui, Pilar Botija, Maria Jose Beltran, Eliseo Albert, Ignacio Torres, Pablo Angel Lopez-Fernandez, Rafael Orti, Juan Francisco Maestre, Gloria Sanchez, David Navarro

Objectives: Near-source tracking of SARS-CoV-2 RNA in the sewage drains serving particular buildings may allow rapid identification of SARS-CoV-2 infection cases or local outbreaks. In this pilot study, we investigated whether this was the case for nursing homes (NH). Methods: The study involved five NH (from A to E) affiliated to the Clinico-Malvarrosa Health Department, Valencia (Spain). These were nursing or mixed nursing/care homes of different sizes, altogether providing care for 472 residents attended by a staff of 309. Near-source sewage samples were screened for presence of SARS-CoV-2 RNA by RT-qPCR at least 5 days per week during the study period. SARS-CoV-2 RNA testing in nasopharyngeal swabs from residents and staff was performed with the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Massachusetts, USA). Results: SARS-CoV-2 RNA was detected in wastewater samples from four of the five NH. SARS-CoV-2 infection cases were documented in three of these four NH. Of the two NH without SARS-CoV-2 infection cases, no SARS-CoV-2 RNA was detected in sewer samples from one facility, while it was repeatedly detected in samples from the other. Presence of SARS-CoV-2 RNA in sewage preceded identification of isolated cases among residents or staff or outbreak declaration in two NH, with lag times ranging from 5 to 19 days. Conclusion: Our study demonstrated that intermittent or persistent detection of SARS-CoV-2 RNA in NH sewers can provide an early warning of subsequent individual cases or outbreaks in these facilities.

101092: Cooperative Communication with Humans Evolved to Emerge Early in Dogs
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Posted 12 Jan 2021

Cooperative Communication with Humans Evolved to Emerge Early in Dogs
202 downloads bioRxiv animal behavior and cognition

Hannah Salomons, Kyle Smith, Megan Callahan-Beckel, Margaret Callahan, Kerinne Levy, Brenda S. Kennedy, Emily Bray, Gitanjali E. Gnanadesikan, Daniel J. Horschler, Margaret Gruen, Jingzhi Tan, Philip White, Evan MacLean, Brian Hare

While we know that dogs evolved from wolves through a process of domestication, it remains unclear how this process may have affected dog cognitive development. Here we tested dog (N=44) and wolf (N=37) puppies, 5-18 weeks old, on a battery of temperament and cognition tasks. Dog puppies were more attracted to humans, read human gestures more skillfully and made more eye contact with humans than wolf puppies. The two species were similarly attracted to objects and performed similarly on nonsocial measures of memory and inhibitory control. These results demonstrate the role of domestication in enhancing the cooperative communication skills of dogs through selection on attraction to humans, which altered developmental pathways.

101093: Limited specificity of SARS-CoV-2 antigen-detecting rapid diagnostic tests at low temperatures
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Posted 03 Feb 2021

Limited specificity of SARS-CoV-2 antigen-detecting rapid diagnostic tests at low temperatures
202 downloads medRxiv infectious diseases

Verena Claudia Haage, Andres Moreira-Soto, Jilian A. Sacks, Victor M Corman, Christian Drosten, Jan Felix Drexler

SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) are available within and outside of health care settings to enable increased access to COVID-19 diagnosis. These environments include provisional testing facilities, lacking temperature control; as outside temperatures fall, recommended testing temperatures cannot be guaranteed. We report impaired specificity in two out of six Ag-RDTs when used at 2-4{degrees}C, indicating that testing in cold settings might cause false-positive results potentially entailing unwarranted quarantine assignments and incorrect incidence estimates.

101094: HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells
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Posted 25 Jan 2021

HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells
202 downloads bioRxiv microbiology

Ann-Kathrin Reuschl, Maitreyi Shivkumar, Dejan Mesner, Laura J Pallett, Jose Afonso Guerra-Assuncao, Rajhmun Madansein, Kaylesh J. Dullabh, Alex Sigal, John P Thornhill, Carolina Herrera, Sarah Fidler, Mahdad Noursadeghi, Mala Maini, Clare Jolly

Human immunodeficiency virus type 1 (HIV-1) replicates in CD4+ T cells leading to profound T cell loss, immunological dysfunction and AIDS. Determining how HIV-1 shapes the immunological niche in which it resides to create a permissive environment is central to informing efforts to limit pathogenesis, disturb viral reservoirs and achieve a cure. A key roadblock in understanding HIV-T cell interactions is the requirement to activate CD4+ T cells in vitro in order to make them permissive to infection. This dramatically alters T cell biology, obscuring native virus-host interactions. Here we show that HIV-1 cell-to-cell spread permits efficient and productive infection of resting CD4+ T cells without the need for prior activation. Infection is preferential for resting memory T cells, is observed with both CXCR4-tropic virus and CCR5-tropic transmitter-founder viruses and results in virus production and onward spreading infection. Strikingly, we find that HIV-1 infection of resting memory CD4+ T cells primes for induction of a tissue-resident memory (TRM)-like phenotype evidenced by upregulation of TRM markers CD69/CXCR6 alongside co-expression of CD49a, PD-1, CD101 as well as transcription factor Blimp-1. Furthermore, we reveal that HIV-1 initiates a transcriptional program that overlaps with the core TRM transcriptional signature. This reprograming depends on the HIV-1 accessory protein Vpr. We propose that HIV-1 infection drives a CD4+ TRM-phenotype potentially sequestering infected cells within tissues to support viral replication and persistence.

101095: Standard and anomalous second waves in the COVID-19 pandemic
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Posted 03 Feb 2021

Standard and anomalous second waves in the COVID-19 pandemic
202 downloads medRxiv infectious diseases

Giovani L. Vasconcelos, Arthur A. Brum, Francisco A. G. Almeida, Antônio M.S. Mâcedo, Gerson C. Duarte-Filho, Raydonal Ospina

We apply a generalised logistic growth model, with time dependent parameters, to describe the fatality curves of the COVID-19 disease for several countries that exhibit a second wave of infections. The model parameters vary as a function of time according to a logistic function, whose two extreme values, i.e., for early and late times, characterise the first and second waves, respectively. We show that the theoretical curves are in excellent agreement with the empirical data for all cases considered. The model also allows for predictions about the time of occurrence and relative severity of the second wave, in comparison to the first wave. It is shown furthermore that the COVID-19 second waves can be generically classified in two main types, namely, standard and anomalous second waves, according as to whether the second wave starts well after or still during the first wave, respectively. We have also observed that the standard second waves tend, in their majority, to be more severe than the corresponding first wave, whereas for anomalous second waves the opposite occurs.

101096: Clinical characteristics and Outcomes of 500 patients with COVID Pneumonia : Results from a Single center(Southend University Hospital)
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Posted 14 Aug 2020

Clinical characteristics and Outcomes of 500 patients with COVID Pneumonia : Results from a Single center(Southend University Hospital)
202 downloads medRxiv epidemiology

Gouri Koduri, Sriya Gokaraju, Maria Darda, Vinod Warrier, Irina Duta, Fiona Hayes, Iman El Sayed, Yasser Noeman Ahmed

Objectives To characterise the clinical features of hospitalised COVID 19 patients in a single centre during the first epidemic wave and explore potential predictive variables associated with outcomes such as mortality and the need for mechanical ventilation, using baseline clinical parameters. Methodology We conducted a retrospective review of electronic records for demographic, clinical and laboratory data, imaging and outcomes for 500 hospitalised patients between February 20th and May 7th 2020 from Southend University Hospital, Essex, UK. Multivariate logistic regression models were used to identify risk factors relevant to outcome. Results The mean age of the cohort admitted to hospital with Covid-19, was 69.4 and 290 (58%) were over 70. The majority were Caucasians, 437 (87%) with less than 2 co-morbidities 280(56%). Most common were hypertension 186(37 %), Cardiovascular disease 178(36 %) and Diabetes 128 (26 %), represented in a larger proportion on the mortality group. Mean CFS was 4 with Non Survivors had significantly higher CFS 5 vs 3 in survivors, p<0.001. In addition, Mean CRP was significantly higher 150 vs 90, p<0.001 in Non Survivors. We observed the baseline predictors for mortality were age, CFS and CRP. Conclusions In this single centre study, older and frailer patients with more comorbidities and a higher baseline CRP and creatinine were risk factors for worse outcomes. Integrated frailty and age based risk stratification are essential, in addition to monitoring SFR (Sp02/Fi02) and inflammatory markers throughout the disease course to allow for early intervention to improve patient outcomes.

101097: Contrasting factors associated with COVID-19-related ICU and death outcomes: interpretable multivariable analyses of the UK CHESS dataset.
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Posted 07 Dec 2020

Contrasting factors associated with COVID-19-related ICU and death outcomes: interpretable multivariable analyses of the UK CHESS dataset.
202 downloads medRxiv health informatics

Massimo Cavallaro, Haseeb Moiz, Matt J Keeling, Noel D McCarthy

Identifying factors associated with severe COVID-19 is a priority to guide clinical care and resource use in this pandemic. This cohort comprised 13954 in-patients with confirmed COVID-19. Study outcomes were death and intensive care unit admission (ICUA). Multivariable logistic regression estimated odd ratios adjusted for 37 covariates (comorbidities, demographic, and others). Gradient boosted decision tree (GBDT) classification generated Shapley values evaluating the impact of covariates for each patient. Deaths due to COVID-19 were associated with immunosuppression due to disease (Odds Ratio 1.39, 95%CI [1.10-1.76]), type-2 diabetes (1.31, [1.17-1.46]), chronic respiratory disease (1.19, [1.05-1.35]), obesity (1.16, [1.01-1.33], age (1.56/10-year increment, [1.52-1.61]), and male sex (1.54, [1.42-1.68]). Associations with ICUA differed in direction (e.g., age, chronic respiratory disease) and in scale, e.g., obesity (3.37, [2.90-3.92]) for some factors. Ethnicity was strongly but variably associated with both outcomes, for example Irish ethnicity is negatively with death but not ICUA. GBDTs had similar performance (ROC-AUC, ICUA 0.83, death 0.68 for GBDT; 0.80 and 0.68 for logistic regression). Shapley explanations overall were consistent with odds ratios. Chronic heart disease, hypertension, other comorbidities, and some ethnicities had Shapley impacts on death ranging from positive to negative among different patients, although consistently associated with ICUA for all. Immunosuppressive disease, type-2 diabetes, and chronic liver and respiratory diseases had positive impacts on death with either positive or negative on ICUA. Very different association of some factors, e.g., obesity, with death and ICUA may guide review of practice. Shapley explanation identified varying effects among patients emphasising the importance of individual patient assessment.

101098: Repetitive but not single blast mild traumatic brain injury increases ethanol responsivity in mice and risky drinking behavior in combat Veterans
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Posted 13 Nov 2020

Repetitive but not single blast mild traumatic brain injury increases ethanol responsivity in mice and risky drinking behavior in combat Veterans
202 downloads medRxiv addiction medicine

Abigail G. Schindler, Britahny Baskin, Barbara Juarez, Suhjung Janet Lee, Rebecca Hendrickson, Katherine Pagulayan, Larry S Zweifel, Murray A. Raskind, Paul EM Phillips, Elaine R Peskind, David G Cook

Mild traumatic brain injury (mTBI) is common in civilians and highly prevalent among military Servicemembers and in contact sports athletes. mTBI, especially within military populations, is often comorbid with posttraumatic stress disorder (PTSD), and can increase health-risk behaviors (e.g., sensation/novelty seeking, impulsivity, risk taking, irritability/aggression) and substance misuse/abuse, but underlying mechanisms remain poorly understood. Using an established mouse model of blast mTBI, here we examined the effects of single (1x) and repetitive (3x) blast exposure on ethanol responsivity using a battery of tests, each associated with distinct aspects of alcohol abuse vulnerability. While both single and repetitive blast exposure increased the sedative properties of high-dose ethanol (with no change in tolerance or metabolism), only repetitive blast exposure potentiated ethanol-induced locomotor stimulation and shifted ethanol intake patterns (i.e., increased consumption front-loading) during intermittent two bottle choice. To establish translational relevance, we next examined self-report responses to the Alcohol Use Disorders Identification Test-Consumption Questions (AUDIT-C) and used a novel unsupervised machine learning approach to investigate whether a history of blast with acute symptoms and mTBI affected drinking behaviors in Iraq and Afghanistan Veterans. AUDIT-C scores were increased in Veterans with a history of blast exposure and subsequent cluster analysis identified a three-cluster solution: low (low intake and low frequency), frequent (low intake but high frequency), and risky (high intake and high frequency), where Veterans with a history of blast mTBI displayed a shift in cluster assignment from frequent to risky, as compared to Veterans who were deployed to Iraq and/or Afghanistan who had no lifetime history of TBI. Together, these results offer new insight regarding how blast mTBI may give rise to increased substance use/misuse and highlight the increased potential for adverse health-risk behaviors following repetitive blast mTBI exposure.

101099: DETECTION OF SURFACE FORCES BY A CELL WALL MECHANOSENSOR
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Posted 11 Dec 2020

DETECTION OF SURFACE FORCES BY A CELL WALL MECHANOSENSOR
202 downloads bioRxiv cell biology

Ramakanth Neeli-Venkata, Ruben Celador, Yolanda Sanchez, Nicolas MINC

Surface receptors of animal cells, such as integrins, promote mechanosensation by forming local clusters as signaling hubs that transduce tensile forces. Walled cells of plants and fungi also feature surface sensors, with long extracellular domains embedded in their cell wall (CW), thought to detect CW injuries and promote repair. How these sensors probe surface forces remains unknown. By studying the conserved CW sensor Wsc1 in fission yeast, we uncovered the formation of micrometer-sized clusters at sites of local force application onto the CW. These clusters form within minutes of CW compression, in dose-dependence with mechanical stress and dissolve upon stress relaxation. Our data support that Wsc1 senses CW mechanical stress and accumulates to local sites of enhanced stress through its CW-associated extracellular WSC domain, independently of canonical polarity, trafficking and downstream CW regulatory pathways. Wsc1 may represent an autonomous module to detect and transduce local surface forces onto the CW.

101100: Coronavirus Disease (COVID-19) Global Prediction Using Hybrid Artificial Intelligence Method of ANN Trained with Grey Wolf Optimizer
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Posted 26 Oct 2020

Coronavirus Disease (COVID-19) Global Prediction Using Hybrid Artificial Intelligence Method of ANN Trained with Grey Wolf Optimizer
202 downloads medRxiv epidemiology

Sina Ardabili, Amir Mosavi, Shahab S. Band, Annamaria R. Varkonyi-Koczy

An accurate outbreak prediction of COVID-19 can successfully help to get insight into the spread and consequences of infectious diseases. Recently, machine learning (ML) based prediction models have been successfully employed for the prediction of the disease outbreak. The present study aimed to engage an artificial neural network-integrated by grey wolf optimizer for COVID-19 outbreak predictions by employing the Global dataset. Training and testing processes have been performed by time-series data related to January 22 to September 15, 2020 and validation has been performed by time-series data related to September 16 to October 15, 2020. Results have been evaluated by employing mean absolute percentage error (MAPE) and correlation coefficient (r) values. ANN-GWO provided a MAPE of 6.23, 13.15 and 11.4% for training, testing and validating phases, respectively. According to the results, the developed model could successfully cope with the prediction task.

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