bluuebunny/crossref_metadata_2025 huggingface dataset:
CONTROLLING COCKROACH POPULATIONS IN HUMAN AND ANIMAL HABITATIONS BY REDUCING FOOD AVAILABILITY
Authors: Hayward William A. , Haseler Luke J. , Muruganandam Maheswari , Gibb James I. , Sibbitt John H. , Sibbitt Wilmer L.
Published: January 2021

Background

Cockroaches, carriers of pathogenic organisms that cause human and animal disease, typically have access to human or pet food in bowls, allowing cockroaches to expand their colonies and infestations.

Hypothesis

We hypothesized that existing anti-ant technology could be converted to anti-cockroach technology by simple design changes.

Methods

A base of various heights was affixed to the bottom of an anti-ant bowl to increase the distance of the anti-ant shield from the native height“x”to the hypothesized cockroach-resistant height“z”. The effects of z =0, 12.7, 15.9, 19.1, 25.4, 44.5, and 57.2 mm were studied. 118.3 cc (4 oz) of dry cat food was used as cockroach bait. The modified anti-ant bowls were placed in a high-intensity cockroach environment during summer nights where the temperatures varied between 23.9-29.4 degrees Celsius for 3 hours and then cockroach counts were performed. Ten runs at each height z were performed.

Results

Mean numbers of infesting cockroaches ± SD at each height z were 21.3±2.9 at 0 mm, 22.0±2.9 at 12.7 mm, 11.2±2.6 at 15.9 mm, 0.9±0.8 at 19.1mm, 0.4±0.5 at 25.4 mm, 0±0 at 44.5 mm, and 0±0 at 57.2 mm (p<0.001 withz≥15.9 mm for all). Cockroach numbers began declining whenz= 15.9 mm and declined to only large cockroaches atz= 25.4 mm. The cockroaches that were able to overcome thez=25.4 mm were the larger American cockroaches that can exceed 76.2 mm (3 inch) in length. However, atz= 44.5 mm and 57.2 mm no cockroaches penetrated the modified bowl.

Conclusions

To defeat the majority of species of cockroaches the anti-insect shield should be at a height of at least 25.4 mm and to defeat the larger American cockroaches preferably greater than 25.4 mm with 44.5 mm and 57.2 mm defeating all tested cockroaches
Evaluation of Drug/Ligand Binding Constants for Human Serum Albumin Using Differential Scanning Calorimetry
Authors: Eskew Matthew W. , Benight Albert S.
Published: January 2021

This paper reports utilization of differential scanning calorimetry measurements to evaluate binding constants for Human Serum Albumin of 28 different drug ligands. Protein/ligand mixtures were prepared at various ligand concentrations and subjected to thermal denaturation analysis by calorimetry. From the measurements, the melting temperature,Tm, and free-energyΔGcal(37°C) for melting ligand-bound Albumin were evaluated as a function of ligand concentration. Concentration dependent behaviors ofΔGcal(37°C) andTmderived from protein/ligand mixtures were used to construct dose-response curves. Model fits of dose-response curves yielded quantitative evaluation of the ligand binding constant,KD, and semi-quantitative estimates of the binding stoichiometry, n. Many of the ligands had known binding affinity for Albumin with binding constants reported in the literature. Evaluated Albumin binding parameters for the ligands impressively agreed with reported literature values determined using other standard experimental methods. These results demonstrated utility of our calorimetry-based process for applications in pre-clinical drug screening.
Evaluation of deep convolutional neural networks for in situ hybridization gene expression image representation
Authors: Abed-Esfahani Pegah , Darwin Benjamin C , Howard Derek , Wang Nick , Kim Ethan , Lerch Jason , French Leon
Published: January 2021

High resolutionin situhybridization (ISH) images of the brain capture spatial gene expression at cellular resolution. These spatial profiles are key to understanding brain organization at the molecular level. Previously, manual qualitative scoring and informatics pipelines have been applied to ISH images to determine expression intensity and pattern. To better capture the complex patterns of gene expression in the human cerebral cortex, we applied a machine learning approach. We propose gene re-identification as a contrastive learning task to compute representations of ISH images. We train our model on a ISH dataset of ~1,000 genes obtained from postmortem samples from 42 individuals. This model reaches a gene re-identification rate of 38.3%, a 13x improvement over random chance. We find that the learned embeddings predict expression intensity and pattern. To test generalization, we generated embeddings in a second dataset that assayed the expression of 78 genes in 53 individuals. In this set of images, 60.2% of genes are re-identified, suggesting the model is robust. Importantly, this dataset assayed expression in individuals diagnosed with schizophrenia. Gene and donor-specific embeddings from the model predict schizophrenia diagnosis at levels similar to that reached with demographic information. Mutations in the most discriminative gene,SCN4B, may help understand cardiovascular associations with schizophrenia and its treatment. We have publicly released our source code, embeddings, and models to spur further application to spatial transcriptomics. In summary, we propose and evaluate gene re-identification as a machine learning task to represent ISH gene expression images.
The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study
Authors: Sepulcri Chiara , Dentone Chiara , Mikulska Malgorzata , Bruzzone Bianca , Lai Alessia , Fenoglio Daniela , Bozzano Federica , Bergna Annalisa , Parodi Alessia , Altosole Tiziana , Delfino Emanuele , Bartalucci Giulia , Orsi Andrea , Di Biagio Antonio , Zehender Gianguglielmo , Ballerini Filippo , Bonora Stefano , De Palma Raffaele , Silvestri Guido , De Maria Andrea , Bassetti Matteo
Published: January 2021

Background

Immunocompromised patients show prolonged shedding of SARS-CoV-2 in nasopharyngeal swabs. We report a case of a prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of COVID-19 in a lymphoma patient.

Methods

Nasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by Real time-PCR (RT-PCR). On five positive nasopharyngeal swabs, we performed viral culture and next generation sequencing. We analysed the patients’ adaptive and innate immunity to characterize T and NK cell subsets.

Findings

SARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive with cycle threshold mean values of 22 ± 1·3 for over 8 months. All five performed viral cultures were positive and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in three out of four COVID-19 clinical relapses and cleared each time after remdesivir treatment. T and NK cells dynamic was different in aviremic and viremic samples and no SARS-CoV-2 specific antibodies were detected throughout the disease course.

Interpretation

In our patient, SARS-CoV-2 persisted with proven infectivity for over eight months. Viremia was associated with COVID-19 relapses and remdesivir treatment was effective in viremia clearance and symptoms remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood that are probably recruited in inflammatory tissue for viral eradication. In addition we found a high level of NK cells repertoire perturbation with a relevant involvement during SARS-CoV-2 viremia.

Funding

None.
Assessment of the knowledge, preferences and concern regarding the prospective COVID- 19 vaccine among adults residing in New Delhi, India-A cross sectional study
Authors: Islam Farzana , Agarwalla Rashmi , Panda Meely , Alvi Yasir , Singh Vishal , Debroy Arup , Ray Arindam , Vadnerkar Amruta , Uttekar Shraddha
Published: January 2021

Background

Understanding the perception and concerns of people about COVID-19 vaccine in developing and populous country like India will help in understanding demand for the vaccine and further tailoring out public health information and education activities before the launch of the vaccine. The study was carried out to assess the present state of knowledge people have about the probable vaccine for COVID-19, to know the preferences of respondents about this vaccine and to learn the expectations and apprehensions of people about features of this prospective COVID-19 vaccine residing in the capital city of India.

Methods

This cross-sectional study was conducted amongst the residents of Delhi, India from July-October 2020. Both offline and online interview method was used to collect date from 513 participants representing various occupational strata. Data was collected on socio demographic variable, vaccine acceptance and concerns regarding COVID-19 vaccine.

Results

Among the study population 79.5% said they will take the vaccine while 8.8% said they were not going to take the vaccine and remaining 11.7% had not yet decided about it. Most of them(78.8%),believed that vaccine would be available to public next year but at the same time half(50.1%) of them believe that it may not be in sufficient amount for everyone to get. More than 50% were willing to pay for the vaccine and 72% felt vaccine should first be given to health workers and high risk group.

Conclusion

The following study has helped to understand the percentage of people who are hesitant to take the vaccine and also the concerns regarding the vaccine. Also since half of the population is willing to pay for the vaccine, a strategical approach considering the various economical classes of people could be applied in a developing country like India.
Super-Spreaders Out, Super-Spreading In: The Effects of Infectiousness Heterogeneity and Lockdowns on Herd Immunity
Authors: Tavori Jhonatan , Levy Hanoch
Published: January 2021

Recently, [8] has proposed that heterogeneity of infectiousness (and susceptibility) across individuals in infectious diseases, plays a major role in affecting the Herd Immunity Thresh-old (HIT). Such heterogeneity has been observed in COVID-19 and is recognized asoverdis-persion(or “super-spreading”). The model of [8] suggests that super-spreaders contribute significantly to the effective reproduction factor,R, and that they are likely to get infected and immune early in the process. Consequently, underR0≈ 3 (attributed to COVID-19), the Herd Immunity Threshold (HIT) is as low as 5%, in contrast to 67% according to the traditional models [1, 2, 4, 10].

This work follows up on [8] and proposes that heterogeneity of infectiousness (susceptibility) has two “faces” whose mix affects dramatically the HIT: (1)Personal-Trait-, and (2)Event-Based-Infectiousness (Susceptibility). The former is a personal trait of specific individuals (super-spreaders) and is nullified once those individuals are immune (as in [8]). The latter is event-based (e.g culturalsuper-spreadingevents) and remains effective throughout the process, even after the super-spreaders immune. We extend [8]’s model to account for these two factors, analyze it and conclude that the HIT is very sensitive to the mix between (1) and (2), and underR0≈ 3 it can vary between 5% and 67%. Preliminary data from COVID-19 suggests that herd immunity is not reached at 5%.

We address operational aspects and analyze the effects of lockdown strategies on the spread of a disease. We find that herd immunity (and HIT) is very sensitive to the lock-down type. While some lockdowns affect positively the disease blocking and increase herd immunity, others haveadverseeffects andreducethe herd immunity.
Evaluation of a Commercial Culture-free Neutralization Antibody Detection Kit for Severe Acute Respiratory Syndrome-Related Coronavirus-2 and Comparison with an Anti-RBD ELISA Assay
Authors: Papenburg Jesse , Cheng Matthew P. , Corsini Rachel , Caya Chelsea , Mendoza Emelissa , Manguiat Kathy , Lindsay L. Robbin , Wood Heidi , Drebot Michael A. , Dibernardo Antonia , Zaharatos Gerasimos , Bazin Reneée , Gasser Romain , Benlarbi Mehdi , Gendron-Lepage Gabrielle , Beaudoin-Bussières Guillaume , Prévost Jérémie , Finzi Andrés , Ndao Momar , Yansouni Cedric P
Published: January 2021

Background

SARS-CoV-2 surrogate neutralization assays that obviate the need for viral culture offer substantial advantages regarding throughput and cost. The cPass SARS-CoV-2 Neutralization Antibody Detection Kit (Genscript) is the first such commercially available assay, detecting antibodies that block RBD/ACE-2 interaction. We aimed to evaluate cPass to inform its use and assess its added value compared to anti-RBD ELISA assays.

Methods

Serum reference panels comprising 205 specimens were used to compare cPass to plaque-reduction neutralization test (PRNT) and a pseudotyped lentiviral neutralization (PLV) assay for detection of neutralizing antibodies. We assessed the correlation of cPass with an ELISA detecting anti-RBD IgG, IgM, and IgA antibodies at a single timepoint and across intervals from onset of symptoms of SARS-CoV-2 infection.

Results

Compared to PRNT-50, cPass sensitivity ranged from 77% - 100% and specificity was 95% - 100%. Sensitivity was also high compared to the pseudotyped lentiviral neutralization assay (93% [95%CI 85-97]), but specificity was lower (58% [95%CI 48-67]). Highest agreement between cPass and ELISA was for anti-RBD IgG (r=0.823). Against the pseudotyped lentiviral neutralization assay, anti-RBD IgG sensitivity (99% [95%CI 94-100]) was very similar to that of cPass, but overall specificity was lower (37% [95%CI 28-47]). Against PRNT-50, results of cPass and anti-RBD IgG were nearly identical.

Conclusions

The added value of cPass compared to an IgG anti-RBD ELISA was modest.
Patients with Asthma and Chronic Obstructive Pulmonary Disease (COPD) have increased levels of plasma inflammatory mediators upregulated in severe COVID-19
Authors: Acevedo Nathalie , Escamilla-Gil Jose Miguel , Espinoza Héctor , Regino Ronald , Ramírez Jonathan , de Arco Lucila Florez , Dennis Rodolfo , Torres-Duque Carlos , Caraballo Luis
Published: January 2021

Background

Chronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear. Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators.

Objective

To perform an immunoproteomic profiling of dysregulated plasma proteins in patients with asthma and COPD and to evaluate their relationship with biomarkers of severe COVID-19.

Methods

Ninety-two proteins were quantified in 315 plasma samples from adult subjects (age 40-90 years) including 118 asthmatics, 99 COPD patients and 98 healthy controls, that have been recruited in two reference pneumology clinics in Colombia before the beginning of the COVID-19 pandemic. Protein levels were compared between each disease group and healthy controls.

Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the “COVID-19 Drug and Gene Set Library” and with known protein biomarkers of severe COVID-19.

Results

Forty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database. An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been found in patients with severe COVID-19.

Conclusions

COPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19. Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19. Our study also suggest that IL-6 levels are increased in some asthmatics and this may influence their immune response to COVID-19.
Preliminary Evidence on Long COVID in children
Authors: Buonsenso Danilo , Munblit Daniel , De Rose Cristina , Sinatti Dario , Ricchiuto Antonia , Carfi Angelo , Valentini Piero
Published: January 2021

There is increasing evidence that adult patients diagnosed with acute COVID-19 suffer from Long COVID initially described in Italy.

To date, data on Long COVID in children are lacking.

We assessed persistent symptoms in pediatric patients previously diagnosed with COVID-19. More than a half reported at least one persisting symptom even after 120 days since COVID-19, with 42.6% being impaired by these symptoms during daily activities. Symptoms like fatigue, muscle and joint pain, headache, insomnia, respiratory problems and palpitations were particularly frequent, as also described in adults.

The evidence that COVID-19 can have long-term impact children as well, including those with asymptomatic/paucisymptomatic COVID-19, highlight the need for pediatricians, mental health experts and policy makers of implementing measures to reduce impact of the pandemic on child’s health.
Design and deployment of an affordable and long-lasting deep-water subsurface fish aggregation device
Authors: Schneider Eric VC , Brooks Edward J , Cortina Michael P , Bailey David M , Killen Shaun S , Leeuwen Travis E Van
Published: January 2021

Fish aggregation devices (FADs) are used worldwide to enhance the efficiency of various fisheries. Devices consist of a floating or subsurface component designed to exploit natural fish behavior, using species’ attraction to structure (e.g.,Sargassumspp.) to aggregate fish and increase capture success in open ocean environments. Concerns have arisen regarding the scale and management of FAD-associated fisheries, however, the efficiency of FADs to aggregate fish also introduces the possibility for FADs to be used as conservation tools to study pelagic species ecology. Building on two successful and several failed deployments of anchored deep-water (>500 m) subsurface (10 m) FADs over three years in The Bahamas, and observations from the subsequent FAD monitoring program, the objectives of the paper are to: 1) provide details and considerations for the design, construction, and deployment of an affordable and durable deep-water subsurface FAD that can be deployed using small boats; and 2) highlight the potential for a long-lasting moored FAD to be used as a sustainable and reliable scientific platform for pelagic species research and conservation, lending specifically to several research applications. This information will be useful for assessing the impacts that FADs and other anthropogenic marine infrastructure have on wild marine species, and their efficacy for conserving pelagic fish through increased encounters for study.
Gaining Insight into the Deformation of Achilles Tendon Entheses in Mice
Authors: Sartori Julian , Köhring Sebastian , Bruns Stefan , Moosmann Julian , Hammel Jörg U.
Published: January 2021

Understanding the biomechanics of tendon entheses is fundamental for surgical repair and tissue engineering, but also relevant in biomimetics and palaeontology. 3D imaging is becoming increasingly important in the examination of soft tissue deformation. But entheses are particularly difficult objects for micro-computed tomography because they exhibit extreme differences in X-ray attenuation. In this article, the ex vivo examination of Achilles tendon entheses from mice using a combination of tensile tests and synchrotron radiation-based micro-computed tomography is reported. Two groups of specimens with different water content are compared with regard to strains and volume changes in the more proximal free tendon and the distal tendon that wraps around theTuber calcanei. Tomograms of relaxed and deformed entheses are recorded with propagation-based phase contrast. The tissue structure is rendered in sufficient detail to enable manual tracking of patterns along the tendon, as well as 3D optical flow analysis in a suitable pair of tomograms. High water content is found to increase strain and to change the strain distribution among proximal and distal tendon. In both groups, the volume changes are higher in the distal than in the proximal tendon. These results support the existence of a compliant zone near the insertion. They also show that the humidity of the specimen environment has to be controlled. Necessary steps to extend the automatic tracking of tissue displacements to all force steps are discussed.
Idiosyncratic learning performance in flies generalizes across modalities
Authors: Smith Matthew , Honegger Kyle S. , Turner Glenn , de Bivort Benjamin
Published: January 2021

Individuals vary in their innate behaviors, even when they have the same genome and have been reared in the same environment. The extent of individuality in plastic behaviors, like learning, is less well characterized. Also unknown is the extent to which intragenotypic differences in learning generalize: if an individual performs well in one assay, will it perform well in other assays? We investigated this using the fruit flyDrosophila melanogaster, an organism long-used to study the mechanistic basis of learning and memory. We found that isogenic flies, reared in identical lab conditions, and subject to classical conditioning that associated odorants with electric shock, exhibit clear individuality in their learning responses. Flies that performed well when an odor was paired with shock tended to perform well when other odors were paired with shock, or when the original odor was paired with bitter taste. Thus, individuality in learning performance appears to be prominent in isogenic animals reared identically, and individual differences in learning performance generalize across stimulus modalities. Establishing these results in flies opens up the possibility of studying the genetic and neural circuit basis of individual differences in learning in a highly suitable model organism.
Paradoxical stabilization of relative position in moving frames
Authors: Özkan Mert , Anstis Stuart , ’t Hart Bernard M. , Wexler Mark , Cavanagh Patrick
Published: January 2021

To capture where things are and what they are doing, the visual system may extract the position and motion of each object relative to its surrounding frame of referencee.g., 1,2. Here we report a particularly powerful example where a paradoxical stabilization is produced by a moving frame. We first take a frame that moves left and right and we flash its right edge before, and its left edge after, the frame’s motion. For all frame displacements tested, the two edges are perceived as stabilized, with the left edge on the left and right edge on the right, separated by the frame’s width as if the frame were not moving. This illusory stabilization holds even when the frame travels farther than its width, reversing the actual spatial order of the two flashes. Despite this stabilization, the motion of the frame is still seen, albeit much reduced, and this hides the paradoxical standstill of relative positions. In a second experiment, two probes are flashed inside the frame at thesamephysical location before and after the frame moves. Despite being physically superimposed, the probes are perceived widely separated, again as if they were seen in the frame’s coordinates and the frame were stationary. This illusory separation is set by the distance of the frame’s travel, independently of its speed. This paradoxical stabilization suggests a link to visual constancy across eye movements where the displacement of the entire visual scene may act as a frame to stabilize the perception of relative locations.
Intelligence and academic performance: Is it all in your head?
Authors: Bottenhorn Katherine L. , Bartley Jessica E. , Riedel Michael C. , Salo Taylor , Bravo Elsa I. , Odean Rosalie , Nazareth Alina , Laird Robert W. , Musser Erica D. , Pruden Shannon M. , Brewe Eric , Sutherland Matthew T. , Laird Angela R.
Published: January 2021

Academic performance relies, in part, on intelligence; however, intelligence quotient (IQ) is limited in predicting academic success. Furthermore, while the search for the biological seat of intelligence predates neuroscience itself, its findings remain conflicting. Here, we assess the interplay between IQ, academic performance, and brain connectivity with behavioral and functional MRI data collected from undergraduate students as they completed an active learning or lecture-based semester-long university physics course. IQ (i.e., full-scale WAIS scores) increased significantly pre-to post-instruction, were associated with physics knowledge and reasoning measures, but were unrelated to overall course grade. IQ was related to brain connectivity during physics-related cognition, but connectivity did not mediate IQ’s association with task performance. These relations depended on students’ sex and instructional environment, providing evidence that physics classroom environment and pedagogy may have a gendered influence on students’ performance. Discussion focuses on opportunities to improve physics reasoning skills for all students.
Laser ablation of the apical sensory organ ofHydroides elegans(Polychaeta) does not inhibit detection of metamorphic cues
Authors: Nedved Brian T. , Freckelton Marnie L. , Hadfield Michael G.
Published: January 2021

Larvae of many marine invertebrates bear an anteriorly positioned apical sensory organ (ASO) presumed to be the receptor for settlement- and metamorphosis-inducing environmental cues, based on its structure, position and observed larval behavior. Larvae of the polychaeteHydroides elegansare induced to settle by bacterial biofilms, which they explore with their ASO and surrounding anteroventral surfaces. A micro-laser was utilized to destroy the ASO and other anterior ciliary structures in competent larvae ofH. elegans. After ablation, larvae were challenged with bacterial biofilmed or clean surfaces and percent metamorphosis was determined. Ablated larvae were also assessed for cellular damage by applying fluorescently tagged FMRF-amide antibodies and observing the larvae by laser-scanning confocal microscopy. While the laser pulses caused extensive damage to the ASO and surrounding cells, they did not inhibit metamorphosis. We conclude that the ASO is not a required receptor site for cues that induce metamorphosis.

Summary Statement

Larvae of the polychaeteHydroides elegansretain the capacity to sense biofilm cues and metamorphose despite removal of their apical sensory organs, the supposed sensors for settlement cues.
Dynamic change and clinical relevance of post-infectious SARS-CoV-2 antibody responses
Authors: Mallon PWG , Tinago W , Leon A Garcia , McCann K , Kenny G , McGettrick P , Green S , Inzitari R , Cotter AG , Feeney ER , Savinelli S , Doran P
Published: January 2021

Background

Although reports suggest that most individuals with COVID-19 develop detectable antibodies post infection, the kinetics, durability, and relative differences between IgM and IgG responses beyond the first few weeks after symptom onset remain poorly understood.

Methods

Within a large, well-phenotyped, diverse, prospective cohort of subjects with and without SARS-CoV-2 PCR-confirmed infection and historical controls derived from cohorts with high prevalence of viral coinfections and samples taken during prior flu seasons, we measured SARS-CoV-2 serological responses (both IgG and IgM) using commercially available assays. We calculated sensitivity and specificity, relationship with disease severity and mapped the kinetics of antibody responses over time using generalised additive models.

Results

We analysed 1,001 samples from 752 subjects, 327 with confirmed SARS-CoV-2 (29.7% with severe disease) spanning a period of 90 days from symptom onset. Sensitivity was lower (44.1-47.1%) early (<10 days) after symptom onset but increased to >80% after 10 days. IgM positivity increased earlier than IgG-targeted assays but positivity peaked between day 32 and 38 post onset of symptoms and declined thereafter, a dynamic that was confirmed when antibody levels were analysed, with more rapid decline observed with IgM. Early (<10 days) IgM but not IgG levels were significantly higher in those who subsequently developed severe disease (signal / cut-off 4.20 (0.75-17.93) versus 1.07 (0.21-5.46), P=0.048).

Conclusions

This study suggests that post-infectious antibody responses in those with confirmed COVID-19 begin to decline relatively early post infection and suggests a potential role for higher IgM levels early in infection predicting subsequent disease severity.
Assessment of The Relationship of REMS and MEWS Scores with Prognosis in Patients Diagnosed with Covid-19 Admitted to the Emergency Department
Authors: Bas Behlul , Senturk Mucahit , Burnaz Tugce Nur , Timur Kubilay , Kalkan Asim
Published: January 2021

Aim

With the rapid and global increase in COVID-19 cases, it is becoming important to identify patients with a risk of mortality and patients that need hospitalization. The aim of this study is to try to predict the mortality rate of COVID patients admitted to the emergency department with rapid scoring systems such as REMS and MEWS and their clinical termination in the emergency department at the end of the first month.

Method

We have designed this study to be a single-centered, prospective and an observational study. A total of 392 patients diagnosed with COVID-19, who were admitted to the emergency department in a 1-month period, were included in the study. REMS and MEWS scores were calculated for each case. Demographic data of patients, clinical outcomes such as discharge, service hospitalization, ICU hospitalization, and first-month mortality were analysed based on these scores. ROC curves were analysed to determine the cut-off value with the help of which REMS and MEWS scores can predict 1-month mortality and hospitalization.

Results

Out of the 392 patients included in the study, the 43.4% (n=170) were female and 56.6% (n=222) were male. The average age of our patients was 48.98±19.49 years. The 1-month mortality rate of our patients was 4.3% (n=17). At the end of the first month, the mortality of patients with a comorbid disease was higher than those who did not (p<0.01). The average of the REMS score was higher in patients with an average mortality of (7.24±3.77) than in patients without it (2.87±3.09), and there was a statistically significant difference between them (p<0.01). Similarly, the average of the MEWS score was higher in patients with an average mortality of (2.76±1.86) than in patients without it (1.65±1.35), and there was a statistically significant difference (p<0.01). The REMS score of patients admitted to the service was higher than that of patients discharged (p<0.01). When the REMS score was determined as 3 cut-off value in ROC analysis, service hospitalization was 5 times higher in patients with a REMS score of 3 and above than in those who were discharged (OR: 1:5.022 95% CI: 3.088-8.168)). REMS and MEWS scores were also higher in ICU patients than in discharged patients (p<0.01).

Conclusion

In predicting the 1-month mortality of ER patients diagnosed with COVID-19, REMS and MEWS scoring systems can be useful and guiding in determining the patients who need hospitalization for emergency physicians. The use of these scoring systems in emergency departments can help predict the clinical outcomes of patients at the time of the initial evaluation, and can also be a practical method of predicting the prognosis of the patients.
Identification of COVID-19 Subtypes Based on Immunogenomic Profiling
Authors: Feng Qiushi , Wang Xiaosheng
Published: January 2021

Although previous studies have shown that the host immune response is crucial in determining clinical outcomes in COVID-19 patients, the association between host immune signatures and COVID-19 patient outcomes remains unclear. Based on the enrichment levels of 11 immune signatures (eight immune-inciting and three immune-inhibiting signatures) in leukocytes of 100 COVID-19 patients, we identified three COVID-19 subtypes: Im-C1, Im-C2, and Im-C3, by clustering analysis. Im-C1 had the lowest immune-inciting signatures and high immune-inhibiting signatures. Im-C2 had medium immune-inciting signatures and high immune-inhibiting signatures. Im-C3 had the highest immune-inciting signatures while the lowest immune-inhibiting signatures. Im-C3 and Im-C1 displayed the best and worst clinical outcomes, respectively, suggesting that antiviral immune responses alleviated the severity of COVID-19 patients. We further demonstrated that the adaptive immune response had a stronger impact on COVID-19 outcomes than the innate immune response. The patients in Im-C3 were younger than those in Im-C1, indicating that younger persons have stronger antiviral immune responses than older persons. Nevertheless, we did not observe a significant association between sex and immune responses in COVID-19 patients. In addition, we found that the type II IFN response signature was an adverse prognostic factor for COVID-19. Our identification of COVID-19 immune subtypes has potential clinical implications for the management of COVID-19 patients.
Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis
Authors: Andrianto  , Al-Farabi Makhyan Jibril , Nugraha Ricardo Adrian , Marsudi Bagas Adhimurda , Azmi Yusuf
Published: January 2021

Background

Several studies have reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect endothelial cells, and endothelial dysfunction is often found in severe cases of coronavirus disease 2019 (COVID-19). To better understand the pathological mechanisms underlying endothelial dysfunction in COVID-19-associated coagulopathy, we conducted a systematic review and meta-analysis to assess biomarkers of endothelial cells in patients with COVID-19.

Methods

A literature search was conducted on online databases for observational studies evaluating biomarkers of endothelial dysfunction and composite poor outcomes in COVID-19 patients.

Results

A total of 1187 patients from 17 studies were included in this analysis. The estimated pooled means for von Willebrand Factor (VWF) antigen levels in COVID-19 patients was higher compared to healthy control (306.42 [95% confidence interval (CI) 291.37-321.48], p<0.001; I2:86%), with the highest VWF antigen levels was found in deceased COVID-19 patients (448.57 [95% CI 407.20-489.93], p<0.001; I2:0%). Meta-analysis showed that higher plasma levels of VWF antigen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 antigen (PAI-1) antigen, and soluble thrombomodulin (sTM) were associated with composite poor outcome in COVID-19 patients ([standardized mean difference (SMD) 0.74 [0.33-1.16], p<0.001; I2:80.4%], [SMD 0.55 [0.19-0.92], p=0.003; I2:6.4%], [SMD 0.33 [0.04-0.62], p=0.025; I2:7.9%], and [SMD 0.55 [0.10-0.99], p=0.015; I2:23.6%], respectively).

Conclusion

The estimated pooled means shows increased levels of VWF antigen in COVID-19 patients. Several biomarkers of endothelial dysfunction, including VFW antigen, t-PA, PAI-1, and sTM, are significantly associated with increased composite poor outcome in patients with COVID-19.

PROSPERO registration number

CRD42021228821
Estimates of global SARS-CoV-2 infection exposure, infection morbidity, and infection mortality rates
Authors: Ayoub Houssein H. , Mumtaz Ghina R. , Seedat Shaheen , Makhoul Monia , Chemaitelly Hiam , Abu-Raddad Laith J.
Published: January 2021

We aimed to estimate, albeit crudely and provisionally, national, regional, and global proportions of respective populations that have been infected with SARS-CoV-2, and to assess infection morbidity and mortality rates, factoring both documented and undocumented infections. The estimates were generated by applying mathematical models to 159 countries and territories. The percentage of the world’s population that has been infected as of 31 December 2020 was estimated at 12.56% (95% CI: 11.17-14.05%). It was lowest in the Western Pacific Region at 0.66% (95% CI: 0.59-0.75%) and highest in the Americas at 41.92% (95% CI: 37.95-46.09%). The global infection fatality rate was 10.73 (95% CI: 10.21-11.29) per 10,000 infections. Globally per 1,000 infections, the infection acute-care bed hospitalization rate was 19.22 (95% CI: 18.73-19.51), the infection ICU bed hospitalization rate was 4.14 (95% CI: 4.10-4.18), the infection severity rate was 6.27 (95% CI: 6.18-6.37), and the infection criticality rate was 2.26 (95% CI: 2.24-2.28). If left unchecked with no interventions, the pandemic would eventually cause 8.18 million (95% CI: 7.30-9.18) deaths, 163.67 million (95% CI: 148.12-179.51) acute-care hospitalizations, 33.01 million (95% CI: 30.52-35.70) ICU hospitalizations, 50.23 million (95% CI: 46.24-54.67) severe cases, and 17.62 million (95% CI: 16.36-18.97) critical cases. The global population remains far below the herd immunity threshold and at risk of repeated waves of infection. Global epidemiology reveals immense regional variation in infection exposure and morbidity and mortality rates.
Genome-wide meta-analysis of pneumonia suggests a role for mucin biology and provides novel drug repurposing opportunities
Authors: Reay William R. , Geaghan Michael P. ,   23andMe Research Team, Cairns Murray J.
Published: January 2021

Pneumonia remains one of the leading causes of death worldwide, particularly amongst the elderly and young children. We performed a genome-wide meta-analysis of lifetime pneumonia diagnosis (N=266,277), that encompassed the largest collection of cases published to date. Genome-wide significant associations with pneumonia were uncovered for the first time beyond the major histocompatibility complex region, with three novel loci, including a signal fine-mapped to a cluster of mucin genes. Moreover, we demonstrated evidence of a polygenic effect of common and low frequency pneumonia associated variation impacting several other mucin genes and O-glycosylation, further suggesting a role for these processes in pneumonia pathophysiology. The pneumonia GWAS was then leveraged to identify drug repurposing opportunities, including evidence that supports the use of lipid modifying agents in the prevention and treatment of the disorder. We also propose how polygenic risk could be utilised for precision drug repurposing through pneumonia risk scores constructed using variants mapped to pathways with known drug targets. In summary, we provide novel insights into the genetic architecture of pneumonia susceptibility, with future study warranted to functionally interrogate novel association signals and evaluate the suitability of the compounds prioritised by this study as repositioning candidates.
Induction of a colitogenic phenotype in Th1 cells depends on IL-23R signaling
Authors: Pawlak Mathias , DeTomaso David , zu Horste Gerd Meyer , Lee Youjin , Nyman Jackson , Dionne Danielle , Wang Chao , Wallrapp Antonia , Burkett Patrick R. , Riesenfeld Samantha J. , Anderson Ana C. , Regev Aviv , Xavier Ramnik J. , Yosef Nir , Kuchroo Vijay K.
Published: January 2021

The cytokine receptor IL-23R plays a fundamental role in inflammation and autoimmunity. However, several observations have been difficult to reconcile under the assumption that only Th17 cells critically depend on IL-23 to acquire a pathogenic phenotype. Here, we report that Th1 cells differentiatedin vitrowith IL-12 + IL-21 show similar levels of IL-23R expression as in pathogenic Th17 cells. We demonstrate that IL-23R is required for Th1 cells to acquire a highly colitogenic phenotype. scRNAseq analysis of intestinal T cells enabled us to identify novel regulators induced by IL-23R-signaling in Th1 cells which differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1 cells inhibited induction of colitis. In this process, we were able to uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver of Th1 cell-mediated tissue inflammation and disease.
The secreted tyrosine kinase VLK is essential for normal platelet activation and thrombus formation
Authors: Revollo Leila , Merrill-Skoloff Glenn , De Ceunynck Karen , Dilks James R. , Bordoli Mattia , Peters Christian G. , Noetzli Leila , Ionescu Andreia , Rosen Vicki , Italiano Joseph E. , Whitman Malcolm , Flaumenhaft Robert
Published: January 2021

Tyrosine phosphorylation of extracellular proteins is observed in cell cultures and in vivo, but little is known about the functional roles of tyrosine phosphorylation of extracellular proteins. Vertebrate Lonesome Kinase (VLK) is a broadly expressed secretory pathway tyrosine kinase present in platelet ɑ-granules. It is released from platelets upon activation and phosphorylates substrates extracellularly. Its role in platelet function, however, has not been previously studied. In human platelets, we identified phosphorylated tyrosines mapped to luminal or extracellular domains of transmembrane and secreted proteins implicated in the regulation of platelet activation. To determine the role of VLK in extracellular tyrosine phosphorylation and platelet function, we generated mice with a megakaryocyte/platelet-specific deficiency of VLK. Platelets from these mice are normal in abundance and morphology, but have dramatic changes in function both in vitro and in vivo. Resting and thrombin-stimulated VLK-deficient platelets demonstrate a significant decrease of several tyrosine phosphobands. Functional testing of VLK-deficient platelets shows decreased PAR4- and collagen-mediated platelet aggregation, but normal responses to ADP. Dense granule and α-granule release are reduced in these platelets. Furthermore, VLK-deficient platelets exhibit decreased PAR4-mediated Akt (S473) and Erk1/2(T202/Y204) phosphorylation, indicating altered proximal signaling. In vivo, mice lacking VLK in megakaryocytes/platelets demonstrate strongly reduced platelet accumulation and fibrin formation following laser-injury of cremaster arterioles compared to controls. These studies demonstrate that the secretory pathway tyrosine kinase VLK is critical for stimulus-dependent platelet activation and thrombus formation, providing the first evidence that a secreted protein kinase is required for normal platelet function.
The balance between toxic versus nontoxic microRNAs determines platinum sensitivity in ovarian cancer
Authors: Patel Monal , Wang Yinu , Bartom Elizabeth T. , Dhir Rohin , Nephew Kenneth P. , Matei Daniela , Murmann Andrea E. , Lengyel Ernst , Peter Marcus E.
Published: January 2021

Numerous micro(mi)RNAs (short noncoding RNAs that negatively regulate gene expression) have been linked to platinum (Pt) sensitivity and resistance in ovarian cancer (OC). miRNA activity occurs when the guide strand of the miRNA, with its seed sequence (pos. 2-7/8), is loaded into the RNA induced silencing complex (RISC) and targets complementary short seed matches in the 3’ untranslated region of mRNAs. Toxic seeds, targeting genes critical for cancer cell survival, have been found in tumor suppressive miRNAs. Many si- and shRNAs can also kill cancer cells via toxic seeds, the most toxic carrying G-rich 6mer seed sequences. We now show that treatment of OC cells with Pt leads to an increase in RISC-bound miRNAs carrying toxic 6mer seeds and a decrease in miRNAs with nontoxic seeds. Pt-resistant cells did not exhibit this toxicity shift but retained sensitivity to cell death mediated by siRNAs carrying toxic 6mer seeds. Analysis of RISC-bound miRNAs in OC patients revealed that the ratio between miRNAs with toxic versus miRNAs with nontoxic seeds was predictive of treatment outcome. Application of the 6mer seed toxicity concept to cancer relevant miRNAs provides a new framework for understanding and predicting cancer therapy responses.
Direct and indirect effects of high temperatures on fledging success in a cooperatively breeding bird
Authors: Bourne Amanda R. , Ridley Amanda R. , Spottiswoode Claire N. , Cunningham Susan J.
Published: January 2021

High temperatures and low rainfall consistently constrain reproduction in arid-zone bird species. Understanding the mechanisms underlying this pattern is critical for predicting how climate change will influence population persistence and to inform conservation and management. In this study, we analysed Southern Pied Babbler Turdoides nestling survival, daily growth rate and adult investment behaviour during the nestling period over three austral summer breeding seasons. High temperatures were associated with lower body mass, shorter tarsi, and reduced daily growth rates of nestlings. Piecewise structural equation modelling suggests that direct impacts of temperature had the strongest influence, followed by changes in provisioning rates by adults to older nestlings.

Adjustments to adult provisioning strategies did not compensate for direct negative effects of high air temperatures on nestling body mass, tarsus and wing length, or daily growth rates. Declining reproductive success during hot weather poses a potentially serious threat to population replacement and persistence as climate change progresses, even for currently common and widespread species. Significantly lower offspring survival as a result of climate warming will likely contribute to the collapse of animal communities well before temperatures regularly approach or exceed lethal tolerance limits. Detailed mechanistic data like these allow us to model the pathways by which high temperature causes nest failure. In turn, this could allow us to design targeted conservation action to effectively mitigate climate effects.
Pose Estimation of Free-Flying Fruit Flies
Authors: Ben-Dov Omri , Beatus Tsevi
Published: January 2021

Insect flight is a complex interdisciplinary phenomenon. Understanding its multiple aspects, such as flight control, sensory integration and genetics, often requires the analysis of large amounts of free flight kinematic data. Yet, one of the main bottlenecks in this field is automatically and accurately extracting such data from multi-view videos. Here, we present a model-based method for pose-estimation of free-flying fruit flies from multi-view high-speed videos. To obtain a faithful representation of the fly with minimum free parameters, our method uses a 3D model that mimics two new aspects of wing deformation: a non-fixed wing hinge and a twisting wing surface. The method is demonstrated for free and perturbed flight. Our method does not use prior assumptions on the kinematics apart from the continuity of one wing angle. Hence, this method can be readily adjusted for other insect species.
Programmable Viscoelasticity in Protein-RNA Condensates with Disordered Sticker-Spacer Polypeptides
Authors: Alshareedah Ibraheem , Moosa Mahdi Muhammad , Pham Matthew , Potoyan Davit A. , Banerjee Priya R.
Published: January 2021

Liquid-liquid phase separation of multivalent proteins and RNAs drives the formation of biomolecular condensates that facilitate membrane-free compartmentalization of subcellular processes. With recent advances, it is becoming increasingly clear that biomolecular condensates are network fluids with time-dependent material properties. Here, employing microrheology with optical tweezers, we reveal molecular determinants that govern the viscoelastic behavior of condensates formed by multivalent Arg/Gly-rich sticker-spacer polypeptides and RNA. These condensates behave as Maxwell fluids with an elastically-dominant rheological response at shorter timescales and a liquid-like behavior at longer timescales. The viscous and elastic regimes of these condensates can be tuned by the polypeptide and RNA sequences as well as their mixture compositions. Our results establish a quantitative link between the sequence- and structure-encoded biomolecular interactions at the microscopic scale and the rheological properties of the resulting condensates at the mesoscale, enabling a route to systematically probe and rationally engineer biomolecular condensates with programmable mechanics.