bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning the Phenomenology of COVID-19 From Early Infection Dynamics
Authors: Magdon-Ismail Malik
Published: March 2020

We present a robust data-driven machine learning analysis of the COVID-19 pandemic from its early infection dynamics, specifically infection counts over time. The goal is to extract actionable public health insights. These insights include the infectious force, the rate of a mild infection becoming serious, estimates for asymtomatic infections and predictions of new infections over time. We focus on USA data starting from the first confirmed infection on January 20 2020. Our methods reveal significant asymptomatic (hidden) infection, a lag of about 10 days, and we quantitatively confirm that the infectious force is strong with about a 0.14% transition from mild to serious infection. Our methods are efficient, robust and general, being agnostic to the specific virus and applicable to different populations or cohorts.
High-risk Human Papillomavirus (16, 18) are not the most common genotypes associated with cervical pre-cancer lesions: a retrospective study at a University Hospital in the Eastern-Province of Saudi Arabia
Authors: Kussaibi Haitham , Dossary Reem Al , Badar Ayesha , Muammar Aroub Omar , Aljohani Raghad Ibrahim
Published: March 2020

Objective

High-risk HPV (human papillomavirus) is found to be responsible for 4.5% of all cancer, especially cervical cancer. The prevalence of high-risk HPV associated with cervical lesions is not well- known in Saudi Arabia. This study aims to highlight the genotypes of high-risk HPV associated with pre- malignant cervical lesions.

Methods

Over 6 years (2013 - 2018), 5091 Pap (Papanicolaou) smears results and 170 high-risk HPV test results were collected from the Information System at King Fahd University Hospital. Statistical analysis was performed using the software SPSS (Statistical Package for Social Sciences).

Results

Out of 5091 Pap smears, only 1.89% (n=96) were abnormal; 0.18% (n=9) were malignant (7 Squamous cell carcinomas and 2 adenocarcinomas), while 1.7% (n=87) showed pre-cancerous lesions, 44 ASCUS (Atypical Squamous Cells of Undetermined Significance), 17 LSIL (Low-grade Squamous Intraepithelial Lesions), 12 HSIL (High-grade Squamous Intraepithelial Lesions), and 14 AGC (Atypical Glandular Cells). Out of 170 patients co-tested for high-risk HPV, only 13.5% (n=23/170) had positive results (5 cases were positive for HPV16, 1 case was positive for both HPV16 and 18, while the remaining 17 cases were positive for high-risk HPV other than 16 or 18), among them, 6.47% (n=11/170) had normal Pap smear, while 7.06% (n=12/170) patients had abnormal Pap smear; 4 ASCUS, 6 LSIL and 2 HSIL. Statistical analysis showed a significant correlation between HPV findings and the Pap smear results (P- value 0.000), however, no significant correlation was found with the patients’ age and/or nationality.

Discussion

Our study showed a unique distribution of high-risk HPV genotypes which reflects different geographical infection patterns. Furthermore, the high association of high-risk HPV with normal Pap smears highlights the need, for all women at risk, to be co-investigated for high-risk HPV. These findings could help in customizing regional vaccine-combinations and screening programs.
Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis
Authors: Ma Chaoqun , Gu Jiawei , Hou Pan , Zhang Liang , Bai Yuan , Guo Zhifu , Wu Hong , Zhang Bili , Li Pan , Zhao Xianxian
Published: March 2020

Background

Recently, Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan, China. Although the clinical features of COVID-19 have been reported previously, data regarding the risk factors associated with the clinical outcomes are lacking.

Objectives

To summary and analyze the clinical characteristics and identify the predictors of disease severity and mortality.

Methods

The PubMed, Web of Science Core Collection, Embase, Cochrane and MedRxiv databases were searched through February 25, 2020. Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations were followed. We extracted and pooled data using random-e□ects meta-analysis to summary the clinical feature of the confirmed COVID-19 patients, and further identify risk factors for disease severity and death. Heterogeneity was evaluated using the I2method and explained with subgroup analysis and meta-regression.

Results

A total of 30 studies including 53000 patients with COVID-19 were included in this study, the mean age was 49.8 years (95% CI, 47.5-52.2 yrs) and 55.5% were male. The pooled incidence of severity and mortality were 20.2% (95% CI, 15.1-25.2%) and 3.1% (95% CI, 1.9-4.2%), respectively. The predictor for disease severity included old age (≥ 50 yrs, odds ratio [OR] = 2.61; 95% CI, 2.29-2.98), male (OR =1.348, 95% CI, 1.195-1.521), smoking (OR =1.734, 95% CI, 1.146-2.626) and any comorbidity (OR = 2.635, 95% CI, 2.098-3.309), especially chronic kidney disease (CKD, OR = 6.017; 95% CI, 2.192-16.514), chronic obstructive pulmonary disease (COPD, OR = 5.323; 95% CI, 2.613-10.847) and cerebrovascular disease (OR = 3.219; 95% CI, 1.486-6.972). In terms of laboratory results, increased lactate dehydrogenase (LDH), C-reactive protein (CRP) and D-dimer and decreased blood platelet and lymphocytes count were highly associated with severe COVID-19 (all for P < 0.001). Meanwhile, old age (≥ 60 yrs, RR = 9.45; 95% CI, 8.09-11.04), followed by cardiovascular disease (RR = 6.75; 95% CI, 5.40-8.43) hypertension (RR = 4.48; 95% CI, 3.69-5.45) and diabetes (RR = 4.43; 95% CI, 3.49-5.61) were found to be independent prognostic factors for the COVID-19 related death.

Conclusions

To our knowledge, this is the first evidence-based medicine research to explore the risk factors of prognosis in patients with COVID-19, which is helpful to identify early-stage patients with poor prognosis and adapt effective treatment.
Modeling and Forecasting Trend of COVID-19 Epidemic in Iran
Authors: Ahmadi Ali , Fadaei Yasin , Shirani Majid , Rahmani Fereydoon
Published: March 2020

Background an objective

COVID-19 is an emerging disease and precise data on its epidemiological profile are not available in the world and Iran. this study aimed to model and determine the epidemic trend and prediction of COVID-19 in Iran.

Methods

This study is a secondary data analysis and mathematical modeling. We used the daily reports of definitive COVID-19 patients released by Iran Ministry of Health and Medical Education. Estimated are based on current trends, Sampling of severe cases, hospitalization and tip of iceberg spread disease and asymptomatic, mild and moderate cases could not be calculated in forecasting. Epidemic projection models of logistic growth differential equations, Gompertz, Von Bertalanffy and least squared error (LSE) method were used to predict the number of cases definitive until April 3, 2020 and April28,2020.

Results

R0in Iran was estimated to be 4.7 that has now fallen to below 2. Given the assumptions in Models, and three different scenarios, the prediction of the patients on April 3, 2020 using three growth models of Von Bertalanffy, Gompertz and LSE were estimated at 19,500, 27,000, and 48,830, respectively. The number of deceased COVID-19 patients was also estimated to be 1707 individuals using the logistic growth model, 3165 ones by Von’s model and 6300 ones according to the LSE method. Assuming continuation of the predicted trend until April 3, 2020, The prediction of the number of patients based on the Gompertz’s and number of dead based on the Von’s model until control the epidemic are estimated about 31000 and 5000 near April 28, 2020 respectively.

Conclusion

The process of controlling the epidemic is tangible. The most ideal scenario is the Von’s model, but it is hard to fulfill and unattainable. If enforcement and public behavior interventions continue with current trends, the control and reduction of the COVID-19 epidemic in Iran will be flat from April 28, until July, 2020 by Gompertz’s model and new cases are expected to decline from the following Iranian new year.
Intensive Care Unit Resource Planning During COVID-19 Emergency at the Regional Level: the Italian case
Authors: Guzzi Pietro Hiram , Tradigo Giuseppe , Veltri Pierangelo
Published: March 2020

Severe acute respiratory syndrome COVID-19 (SARS-CoV-2) has been declared a worldwide emergency and a pandemic disease by the World Health Organisation (WHO). It started in China in December 2019, and it is currently rapidly spreading throughout Italy, which is now the most affected country after China. There is great attention for the diffusion and evolution of the COVID-19 infection which started from the north (particularly in the Lombardia region) and it is now rapidly affecting other Italian regions. We investigate on the impact of patients hospitalisation in Intensive Care Units (ICUs) at a regional and subregional granularity. We propose a model derived from well-known models in epidemic to estimate the needed number of places in intensive care units. The model will help decision-makers to plan resources in the short and medium-term in order to guarantee appropriate treatments to all patients needing it. We analyse Italian data at regional level up to March 15th aiming to: (i) support health and government decision-makers in gathering rapid and efficient decisions on increasing health structures capacities (in terms of ICU slots) and (ii) define a scalable geographic model to plan emergency and future COVID-19 patients management using reallocating them among health structures. Finally, the here proposed model can be useful in countries where COVID-19 is not yet strongly diffused.
Pan-cancer analysis identified inflamed microenvironment associated multi-omics signatures
Authors: Wang Ben , Liu Mengmeng , Ran Zhujie , Li Xin , Li Jie , Ou Yunsheng
Published: March 2020

Background

Immunotherapy has revolutionized cancer therapy. However, responses are not universal. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, how different tumors shape their tumor microenvironment remains a critical unsolved problem. A deeper insight into the molecular characteristics of inflamed tumor microenvironment may be needed.

Materials and methods

Here, based on single-cell RNA sequencing technology and TCGA pan-cancer cohort, we investigated multi-omics molecular features of tumor microenvironment phenotypes. Based on single-cell RNA-seq analysis, we classified pan-cancer tumor samples into inflamed or non-inflamed tumor and identified molecular features of these tumors. Analysis of integrating identified gene signatures with a drug-genomic perturbation database identified multiple drugs which may be helpful for converting non-inflamed tumors to inflamed tumors.

Results

Our results revealed several inflamed/non-inflamed tumor microenvironments-specific molecular characteristics. For example, inflamed tumors highly expressed miR-650 and lncRNA including MIR155HG and LINC00426, these tumors showed activated cytokines-related signaling pathways. Interestingly, non-inflamed tumors tended to express several genes related to neurogenesis. Multi-omics analysis demonstrated the neuro phenotype transformation may be induced by hypomethylated promoters of these genes and down-regulated miR-650. Drug discovery analysis revealed histone deacetylase inhibitors may be a potential choice for helping favorable tumor microenvironment phenotype transformation and aiding current immunotherapy.

Conclusion

Our results provide a comprehensive molecular-level understanding of tumor cell-immune cell interaction and may have profound clinical implications.
The tempo of trophic evolution in small-bodied primates
Authors: Scott Jeremiah E.
Published: March 2020

Objectives

As a primary trophic strategy, insectivory is uncommon and unevenly distributed across extant primates. This pattern is partly a function of the challenges that insectivory poses for large-bodied primates. In this study, I demonstrate that the uneven distribution is also a consequence of variation in the rate of trophic evolution among small-bodied lineages.

Methods

The sample consisted of 307 species classified by primary trophic strategy and body size, creating an ordered three-state character: small-insectivorous, small-herbivorous, and large-herbivorous. I tested for rate heterogeneity by partitioning major clades from the rest of the primate tree and estimating separate rates of transition between herbivory and insectivory for small-bodied lineages in each partition.

Results

Bayesian analysis of rate estimates indicates that a model with two rates of trophic evolution provides the best fit to the data. According to the model, lorisiforms have a trophic rate that is 4–6 times higher than the rate for other small-bodied lineages.

Conclusions

The rate heterogeneity detected here suggests that lorisiforms are characterized by traits that give them greater trophic flexibility than other primates. Previous discussions of trophic evolution in small-bodied primates focused on the low frequency of insectivory among anthropoids and the possibility that diurnality makes insectivory unlikely to evolve or persist. The present study challenges this idea by showing that a common transition rate can explain the distribution of insectivory in small-bodied anthropoids and nocturnal lemurs and tarsiers. The results of this study offer important clues for reconstructing trophic evolution in early primates.
Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence
Authors: Nickbakhsh Sema , Ho Antonia , Marques Diogo F.P. , McMenamin Jim , Gunson Rory N. , Murcia Pablo R.
Published: March 2020

Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal human coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.
Variants inSTAU2associate with metformin response in a type 2 diabetes cohort: a pharmacogenomics study using real-world electronic health record data
Authors: Zhang Yanfei , Hu Ying , Ho Kevin , Hartzel Dustin N. , Abedi Vida , Zand Ramin , Williams Marc S. , Lee Ming Ta M.
Published: March 2020

Type 2 diabetes mellitus (T2DM) is a major health and economic burden because of the seriousness of the disease and its complications. Improvements in short- and long-term glycemic control is the goal of diabetes treatment. To investigate the longitudinal management of T2DM at Geisinger, we interrogated the electronic health record (EHR) information and identified a T2DM cohort including 125,477 patients using the Electronic Medical Records and Genomics Network (eMERGE) T2DM phenotyping algorithm. We investigated the annual anti-diabetic medication usage and the overall glycemic control using hemoglobin A1c (HbA1c). Metformin remains the most frequently medication despite the availability of the new classes of anti-diabetic medications. Median value of HbA1c decreased to 7% in 2002 and since remained stable, indicating a good glycemic management in Geisinger population. Using metformin as a pilot study, we identified three groups of patients with distinct HbA1c trajectories after metformin treatment. The variabilities in metformin response is mainly explained by the baseline HbA1c. The pharmacogenomic analysis of metformin identified a missense variant rs75740279 (Leu/Val) for STAU2 associated with the metformin response. This strategy can be applied to study other anti-diabeticmedications. Such research will facilitate the translational healthcare for better T2DM management.
Predicting the epidemic trend of COVID-19 in China and across the world using the machine learning approach
Authors: Li Mengyuan , Zhang Zhilan , Jiang Shanmei , Liu Qian , Chen Canping , Zhang Yue , Wang Xiaosheng
Published: March 2020

Background

Although COVID-19 has been well controlled in China, it is rapidly spreading outside the country and may have catastrophic results globally without implementation of necessary mitigation measures. Because the COVID-19 outbreak has made comprehensive and profound impacts on the world, an accurate prediction of its epidemic trend is significant. Although many studies have predicted the COVID-19 epidemic trend, most have used early-stage data and focused on Chinese cases.

Methods

We first built models to predict daily numbers of cumulative confirmed cases (CCCs), new cases (NCs), and death cases (DCs) of COVID-19 in China based on data from January 20, 2020, to March 1, 2020. Based on these models, we built models to predict the epidemic trend across the world (outside China). We also built models to predict the epidemic trend in Italy, Spain, Germany, France, UK, and USA where COVID-19 is rapidly spreading.

Results

The COVID-19 outbreak will have peaked on February 22, 2020, in China and will peak on May 22, 2020, across the world. It will be basically under control in early April 2020 in China and late August 2020 across the world. The total number of COVID-19 cases will reach around 89,000 in China and 6,126,000 across the world during the epidemic. Around 4,000 and 290,000 people will die of COVID-19 in China and across the world, respectively. The COVID-19 outbreak will have peaked recently in Italy and will peak in Spain, Germany, France, UK, and USA within two weeks.

Conclusion

The COVID-19 outbreak is controllable in the foreseeable future if comprehensive and stringent control measures are taken.
Prediction of protein mutational free energy: benchmark and sampling improvements increase classification accuracy
Authors: Frenz Brandon , Lewis Steven , King Indigo , Park Hahnbeom , DiMaio Frank , Song Yifan
Published: March 2020

Software to predict the change in protein stability upon point mutation is a valuable tool for a number of biotechnological and scientific problems. To facilitate the development of such software and provide easy access to the available experimental data, the ProTherm database was created. Biases in the methods and types of information collected has led to disparity in the types of mutations for which experimental data is available. For example, mutations to alanine are hugely overrepresented whereas those involving charged residues, especially from one charged residue to another, are underrepresented. ProTherm subsets created as benchmark sets that do not account for this often underrepresented certain mutational types. This issue introduces systematic biases into previously published protocols’ ability to accurately predict the change in folding energy on these classes of mutations. To resolve this issue, we have generated a new benchmark set with these problems corrected. We have then used the benchmark set to test a number of improvements to the point mutation energetics tools in the Rosetta software suite.
The p53-p21 axis plays a central role in lymphatic homeostasis and disease
Authors: Mylavarapu Rohan , Kulikauskas Molly R. , Dierkes Cathrin , Sobhani Nema , Mangette Michelle , Finlon Jeffrey , Stevens Wanida , Arbab Farinaz , Box Neil F. , Lovell Mark , Muley Ajit , Shawber Carrie J. , Tamburini Beth , Kiefer Friedemann , Terzian Tamara
Published: March 2020

Activation of the transcription factor p53 has been associated with several developmental syndromes. In normal tissues, p53 is kept at very low undetectable physiological levels. When triggered by cellular stressors, p53 prompts important anti-proliferative and apoptotic programs part of its tumor suppressor activity or as the guardian of tissue homeostasis.

We generated two murine models that display cutaneous hemorrhaging, severe edema, and distended blood-filled lymphatic vessels at late-gestation due to overactive p53 uniquely affecting lymphatic endothelial cells during development. Overactive p53 operated distinctively through anti-proliferative route in this tissue resulting in a decrease in initial lymphatics that normally absorb interstitial fluid. Remarkably, genetic or pharmacologic normalization of p53 restored lymphatic homeostasis and reversed lymphatic phenotypes. In parallel, several human lymphatic disease tissues exhibited high p53 levels exclusively in the lymphatic endothelium while p53 remained undetectable in surrounding arterial or venous vessels.

We report here, for the first time, an extended role that the p53 pathway plays in the genesis of lymphatic homeostasis deficiencies opening the way for new therapeutic avenues for these rare, poorly understood, and incurable lymphatic maladies.
Polycyclic Aromatic Hydrocarbon, Heavy Metal, and Derivable Metabolic Water and Energy of Catle Hides Processed by Singeing
Authors: Woko Eze C. , Ibegbulem C. O. , Alisi Chinwe S.
Published: March 2020

Meat is consumed as source of protein, processed cattle hide popularly known asKandain southeastern Nigeria is consumed as a substitute for meat. The commercial method of processing this very food delicacy through singeing with scrap tyre, or firewood has posed question marks over the contamination status of theKanda. This study therefore investigated the heavy metal, polycyclic aromatic hydrocarbon (PAHs) content, proximate composition, and also calculated the derivable metabolic water and energy content ofKandasinged with scrap tyre, and firewood. Singeing significantly reduced (p < 0.05) the moisture, ash, fibre and carbohydrate contents of the hide while it increased the protein content; increased (p < 0.05) the iron (Fe) concentration of the hide though the concentration of iron detected was far below the average lethal dose allowed in meat and meat products and elevated (p < 0.05) the PAH concentration of the hides. However, the hides singed with firewood showed higher (p < 0.05) concentrations of benzo[a]pyrene. With the exception of naphthalene, 2-methylnaphthalene, acenenaphthalene and indeno [1,2,3-cd] pyrene all the 16 Environmental Protection Agency (EPA) priority PAHs evaluated showed concentration above 0.0001 ppm (0.1 μg/kg) in at least one of the singed samples. Also, Singeing significantly increased (p < 0.05) the derivable metabolic water and energy contents of the cattle hides. In conclusion, while consuming singed cattle hide (Kanda) may offer higher energy content and derivable metabolic water, it may in the long term expose the consumer to health hazards associated with heavy metal and PAH contamination.
Profiling microglia from AD donors and non-demented elderly in acute human post-mortem cortical tissue
Authors: Alsema Astrid M. , Jiang Qiong , Kracht Laura , Gerrits Emma , Dubbelaar Marissa L. , Miedema Anneke , Brouwer Nieske , Woodbury Maya , Wachter Astrid , Xi Hualin S. , Möller Thomas , Biber Knut P. , Kooistra Susanne M. , Boddeke Erik W.G.M , Eggen Bart J.L.
Published: March 2020

Microglia are the tissue-resident macrophages of the central nervous system (CNS). Recent studies based on bulk and single-cell RNA sequencing in mice indicate high relevance of microglia with respect to risk genes and neuro-inflammation in Alzheimer’s disease. Here, we investigated microglia transcriptomes at bulk and single cell level in non-demented elderly and AD donors using acute human post-mortem cortical brain samples. We identified 9 human microglial subpopulations with heterogeneity in gene expression. Notably, gene expression profiles and subcluster composition of microglia did not differ between AD donors and non-demented elderly in bulk RNA sequencing nor in single-cell sequencing.
Revisiting the Association between Human Leukocyte Antigen and End-Stage Renal Disease
Authors: Noureen Naila , Shah Farhad Ali , Lisec Jan , Usman Hina , Khalid Mohammad , Munir Rimsha , Zaidi Nousheen
Published: March 2020

Multiple works have studied possible associations between human leukocyte antigen (HLA) alleles and end stage renal disease (ESRD) showing, however, contradictory and inconsistent results. Here, we revisit the association between ESRD and HLA antigens, comparing HLA polymorphism (at HLA-A, -B, -C, -DRB1, -DQB1 and DQA1 loci) in ESRD patients (n=497) and controls (n=672). Our data identified several HLA alleles that displayed a significant positive or negative association with ESRD. We also determined whether heterozygosity or homozygosity of the ESRD-associated HLA alleles at different loci could modify the prevalence of the disease. Few HLA allele combinations displayed significant associations with ESRD among which HLA-A*3–HLA-A*26 combination showed the highest strength of association (OR= 4.488, P≤ 0.05) with ESRD. Interestingly, the age of ESRD onset was not affected by HLA allele combinations at different loci. We also performed an extensive literature analysis to determine whether the association of HLA to ESRD can be similar across different ethnic groups. Our analysis showed at least for certain alleles, HLA-A*11, HLA-DRB1*11, and HLA-DRB1*4, a significant association of HLA to ESRD in different ethnic groups. The findings of our study will help in determining possible protective or susceptible roles of various HLA alleles in ESRD.
OrganoidTracker: efficient cell tracking using machine learning and manual error correction
Authors: Kok Rutger N.U. , Hebert Laetitia , Huelsz-Prince Guizela , Goos Yvonne J. , Zheng Xuan , Bozek Katarzyna , Stephens Greg J. , Tans Sander J. , van Zon Jeroen S.
Published: March 2020

Time-lapse microscopy is routinely used to follow cells within organoids, allowing direct study of division and differentiation patterns. There is an increasing interest in cell tracking in organoids, which makes it possible to study their growth and homeostasis at the single-cell level. As tracking these cells by hand is prohibitively time consuming, automation using a computer program is required. Unfortunately, organoids have a high cell density and fast cell movement, which makes automated cell tracking difficult. In this work, a semi-automated cell tracker has been developed. To detect the nuclei, we use a machine learning approach based on a convolutional neural network. To form cell trajectories, we link detections at different time points together using a min-cost flow solver. The tracker raises warnings for situations with likely errors. Rapid changes in nucleus volume and position are reported for manual review, as well as cases where nuclei divide, appear and disappear. When the warning system is adjusted such that virtually error-free lineage trees can be obtained, still less than 2% of all detected nuclei positions are marked for manual analysis. This provides an enormous speed boost over manual cell tracking, while still providing tracking data of the same quality as manual tracking.
An automated light trap to monitor moths (Lepidoptera) using computer vision-based tracking and deep learning
Authors: Bjerge Kim , Nielsen Jakob Bonde , Sepstrup Martin Videbæk , Helsing-Nielsen Flemming , Høye Toke Thomas
Published: March 2020

Insect monitoring methods are typically very time consuming and involves substantial investment in species identification following manual trapping in the field. Insect traps are often only serviced weekly resulting in low temporal resolution of the monitoring data, which hampers the ecological interpretation. This paper presents a portable computer vision system capable of attracting and detecting live insects. More specifically, the paper proposes detection and classification of species by recording images of live individuals attracted to a light trap. An Automated Moth Trap (AMT) with multiple light sources and a camera was designed to attract and monitor live insects during twilight and night hours. A computer vision algorithm referred to as Moth Classification and Counting (MCC), based on deep learning analysis of the captured images, tracked and counted the number of insects and identified moth species. Observations over 48 nights resulted in the capture of more than 250,000 images with an average of 5,675 images per night. A customized convolutional neural network was trained on 2,000 labelled images of live moths represented by eight different species, achieving a high validationF1-score of 0.93. The algorithm measured an average classification and trackingF1-score of 0.71 and a tracking detection rate of 0.79. Overall, the proposed computer vision system and algorithm showed promising results as a low-cost solution for non-destructive and automatic monitoring of moths.
Molecular Basis of Host-Adaptation Interactions between Influenza Virus Polymerase PB2 Subunit and ANP32A
Authors: Zarco Aldo Camacho , Kalayil Sissy , Maurin Damien , Salvi Nicola , Delaforge Elise , Milles Sigrid , Jensen Malene Ringkjøbing , Hart Darren J. , Cusack Stephen , Blackledge Martin
Published: March 2020

Avian influenza polymerase undergoes host adaptation in order to efficiently replicate in human cells. Adaptive mutants are localised on the C-terminal (627-NLS) domains of the PB2 subunit. In particular mutation of PB2 residue 627 from E to K in avian polymerase rescues activity in mammalian cells. A host transcription regulator ANP32A, comprising a long C-terminal intrinsically disordered domain (IDD), has also been shown to be responsible for this viral adaptation. Human ANP32A IDD lacks a 33 residue insertion compared to avian ANP32A, a deletion that restricts avian influenza polymerase activity in mammalian cells. We determined conformational descriptions of the highly dynamic complexes between 627E and 627K forms of the 627-NLS domains of PB2 and avian and human ANP32A. The negatively charged intrinsically disordered domain of human ANP32A transiently binds to a basic face of the 627 domain, exploiting multiple binding sites to maximize affinity for 627-NLS. This interaction also implicates residues 590 and 591 that are responsible for human-adaptation of the the 2009 pandemic influenza polymerase. The presence of 627E interrupts the polyvalency of the interaction, an effect that is compensated by extending the interaction surface and exploiting an avian-unique motif in the unfolded domain that interacts with the 627-NLS linker. In both cases the interaction favours the open, dislocated form of the 627-NLS domains. Importantly the two binding modes exploited by human- and avian-adapted PB2 are strongly abrogated in the cross interaction between avian polymerase and human ANP32A, suggesting that this molecular specificity may be related to species adaptation. The observed binding mode is maintained in the context of heterotrimeric influenza polymerase, placing ANP32A in the immediate vicinity of known host-adaptive PB2 mutants. This study provides a molecular framework for understanding the species-specific restriction of influenza polymerase by ANP32A and will inform the identification of new targets for influenza inhibition.
Start codon disruption with CRISPR/Cas9 prevents murine Fuchs’ endothelial corneal dystrophy
Authors: Uehara Hironori , Zhang Xiaohui , Pereira Felipe , Narendran Siddharth , Choi Susie , Bhuvanagiri Sai , Liu Jinlu , Kumar Sangeetha Ravi , Bohner Austin , Carroll Lara , Archer Bonnie , Zhang Yue , Liu Wei , Gao Guangping , Ambati Jayakrishna , Jun Albert S , Ambati Balamurali K.
Published: March 2020

A missense mutation of collagen type VIII alpha 2 chain (COL8A2) gene leads to early onset Fuchs’ endothelial corneal dystrophy (FECD), which progressively impairs vision through loss of corneal endothelial cells. We demonstrate that CRISPR/Cas9-based postnatal gene editing achieves structural and functional rescue in a mouse model of FECD. A single intraocular injection of an adenovirus encoding both the Cas9 gene and guide RNA (Ad-Cas9-Col8a2gRNA), efficiently knocked down mutant COL8A2 expression in corneal endothelial cells, prevented endothelial cell loss, and rescued corneal endothelium pumping function in adult Col8a2 mutant mice. There were no adverse sequelae on histology or electroretinography. Col8a2 start codon disruption represents a non-surgical strategy to prevent vision loss in early-onset FECD. As this demonstrates the ability of Ad-Cas9-gRNA to restore phenotype in adult post-mitotic cells, this method may be widely applicable to adult-onset diseases, even in tissues affected with disorders of non-reproducing cells.
Stochastic Epigenetic Dynamics of Gene Switching
Authors: Bhattacharyya Bhaswati , Wang Jin , Sasai Masaki
Published: March 2020

Epigenetic modifications of histones crucially affect the eukaryotic gene activity. We theoretically analyze the dynamical effects of histone modifications on gene switching by using the Doi-Peliti operator formalism of chemical reaction kinetics. The calculated probability flux in self-regulating genes shows a distinct circular flow around basins in the landscape of the gene state distribution, giving rise to hysteresis in gene switching. In contrast to the general belief that the change in the amount of transcription factor (TF) precedes the histone state change, the flux drives histones to be modified prior to the change in the amount of TF in the self-regulating circuits. The flux-landscape analyses elucidate the nonlinear nonequilibrium mechanism of epigenetic gene switching.
Population dynamics of decision making in temperate bacteriophages
Authors: Lang Moritz , Pleška Maroš , Guet Cǎlin C.
Published: March 2020

Due to their ability to choose between lysis and lysogeny, temperate bacteriophages represent a classic model system to study the molecular basis of decision making. The coinfection of individual bacteria by multiple, genetically identical phages is known to alter the infection outcome and favor lysogeny over lytic development. However, it is not clear what role the ability of individual phages to sense and respond to coinfections plays in the phage-host infection dynamics at the population level. To address this question, we developed a full-stochastic model to capture the interaction dynamics between billions of bacteria and phages with single-cell and -phage resolution. While, at the level of individual bacteria, the probability of coinfections depends mainly on the phage concentration at the time of infection, the average number of coinfections at the population level is primarily determined by the relative growth rate of phage. Because the maximum attainable phage growth rate is constrained by basic life history parameters, the average number of coinfections has an upper bound of around two. However, for a broad range of conditions, the average number of coinfections stays well below this value. Consequently, we find that coinfections provide only very limited information to individual phages about the state of the infection at the population level. Nevertheless, this information can still provide a strong competitive advantage for phages that base fate decisions on the number of coinfections.
On the ecology and distribution of steelhead(Oncorhynchus mykiss)in California’s Eel River
Authors: Kannry Samantha H. , O’Rourke Sean M. , Kelson Suzanne J , Miller Michael R
Published: March 2020

Preservation of life-history and other phenotypic complexity is central to the resilience of Pacific salmon stocks. Steelhead (Oncorhynchus mykiss) express a diversity of life history strategies such as the propensity to migrate (anadromy/residency) and the timing and state of maturation upon return to freshwater (run-timing), providing an opportunity to study adaptive phenotypic complexity. Historically, the Eel River supported upwards of one million salmon and steelhead, but the past century has seen dramatic declines of all salmonids in the watershed. Here we investigate life history variation in Eel River steelhead by using Rapture sequencing, on thousands of individuals, to genotype the region diagnostic for run-timing (GREB1L) and the region strongly associated with residency/anadromy (OMY5) in the Eel River and other locations, as well as determine patterns of overall genetic differentiation. Our results provide insight into many conservation related issues. For example, we found distinct segregation between winter and summer-run steelhead correlated with flow dependent barriers in major forks of the Eel; that summer-run steelhead inhabited the upper Eel prior to construction of an impassable dam, and that both life-history and overall genetic diversity have been maintained in the resident trout population above; and no evidence of the summer-run allele in the South Fork Eel, indicating that summer run-timing cannot be expected to arise from standing genetic variation in this and other populations that lack the summer-run phenotype. The results presented in this study provide valuable information for designing future restoration and management strategies forO. mykissin Northern California and beyond.
Activation of JUN in fibroblasts promotes pro-fibrotic programme and modulates protective immunity
Authors: Cui Lu , Chen Shih-Yu , Lerbs Tristan , Lee Jin-Wook , Domizi Pablo , Gordon Sydney , Kim Yong-hun , Nolan Garry , Betancur Paola , Wernig Gerlinde
Published: March 2020

In pulmonary fibrosis, the transcription factor JUN is highly expressed in the fibrotic foci. Its induction in adult mice drives lung fibrosis, which is abrogated by administration of anti-CD47. Here, we use high-dimensional mass cytometry to profile protein expression and the secretome of individual fibroblasts and leukocytes from pulmonary fibrosis patients. We show thatJUNis activated in fibroblasts derived from fibrotic lungs which also demonstrated increased CD47 and PD-L1 expression. Using ATAC-seq and ChIP-seq, we found that activation ofJUNin fibroblasts rendered enhancers ofCD47andPD-L1accessible, an observation that reporter assays corroborated. Meanwhile we detected increased IL-6 signaling which amplified both JUN-mediatedCD47-enhancer activity and protein expression in fibrotic lung fibroblasts. Using anin vivomouse model of fibrosis, we found two distinct mechanisms by which blocking IL-6, CD47, and PD-L1 reversed fibrosis—increased phagocytosis of profibrotic fibroblasts and elimination of suppressive effects on adaptive immunity. Our results identify specific immune mechanisms that promote the fibrotic process and suggest a complementary therapeutic approach that could be used alongside conventional anti-fibrotics for pulmonary fibrosis diseases.
Conversion of marginal land into switchgrass conditionally accrues soil carbon and reduces methane consumption
Authors: Bates Colin T. , Escalas Arthur , Kuang Jialiang , Hale Lauren , Wang Yuan , Herman Don , Nuccio Erin E. , Wang Xiaoling , Fu Ying , Tian Renmao , Wang Gangsheng , Ning Daliang , Yang Yunfeng , Wu Liyou , Pett-Ridge Jennifer , Saha Malay , Craven Kelly , Firestone Mary , Zhou Jizhong
Published: March 2020

Switchgrass (Panicum virgatumL.) is a perennial C4grass native to tallgrass prairies of the Central US, and a promising bioenergy feedstock. Switchgrass can be cultivated on soils with low nutrient contents and its rooting depth, of up to 2 m, has brought attention to the crop as a potential mechanism to sequester and build soil carbon (C). Switchgrass, therefore, offers multifaceted benefits on degraded soils by enhancing soil organic matter content. However, to evaluate the sustainability of switchgrass-based biofuel production, it is crucial to understand the impacts of land conversion and switchgrass establishment on biotic/abiotic characteristics of various soils. In this study, we characterized the ecosystem-scale consequences of switchgrass growing at two highly-eroded, ‘Dust Bowl’ remnant field sites from Oklahoma US, with silt-loam (SL) or clay-loam (CL) soil textures having low nitrogen (N), phosphorus (P), and C contents. Paired plots at each site, including fallow control and switchgrass-cultivated, were assessed. Our results indicated that switchgrass significantly increased soil C at the SL site and reduced microbial diversity at the CL site. The CL site exhibited significantly higher CO2flux and higher respiration from switchgrass plots. Strikingly, switchgrass significantly reduced the CH4consumption by an estimated 39% for the SL site and 47% for the CL site. Structural equation modeling identified soil temperature, P content, and soil moisture levels as the most influential factors regulating both CO2and CH4fluxes. CO2flux was also influenced by microbial biomass while CH4flux was influenced by microbial diversity. Together, our results suggest that site selection by soil type is a crucial factor in improving soil C stocks and mitigating greenhouse gas (GHG) fluxes, especially considering our finding that switchgrass reduced methane consumption, implying that carbon balance considerations should be accounted for to fully evaluate the sustainability of switchgrass cultivation.
Scleraxis is required for the growth of adult tendons in response to mechanical loading
Authors: Gumucio Jonathan P , Schonk Martin M , Kharaz Yalda A , Comerford Eithne , Mendias Christopher L
Published: March 2020

Scleraxis is a basic helix-loop-helix transcription factor that plays a central role in promoting tenocyte proliferation and matrix synthesis during embryonic tendon development. However, the role of scleraxis in the growth and adaptation of adult tendons is not known. We hypothesized that scleraxis is required for tendon growth in response to mechanical loading, and that scleraxis promotes the specification of progenitor cells into tenocytes. We conditionally deleted scleraxis in adult mice using a tamoxifen-inducible Cre-recombinase expressed from theRosa26locus (ScxΔ), and then induced tendon growth inScx+andScxΔadult mice via plantaris tendon mechanical overload. Compared to the wild typeScx+group,ScxΔmice demonstrated blunted tendon growth. Transcriptional and proteomic analyses revealed significant reductions in cell proliferation, protein synthesis, and extracellular matrix genes and proteins. Our results indicate that scleraxis is required for mechanically-stimulated adult tendon growth by causing the commitment of CD146+pericytes into the tenogenic lineage, and by promoting the initial expansion of newly committed tenocytes and the production of extracellular matrix proteins.
A multiscale 3D chemotaxis assay reveals bacterial navigation mechanisms
Authors: Grognot Marianne , Taute Katja M.
Published: March 2020

How bacteria navigate environmental chemical gradients has implications ranging from health to climate science. The underlying behavioral mechanisms are unknown for most species due to a lack in techniques bridging scales from individual 3D motility behavior to the statistical power required to assess the resulting performance. We present the first demonstration of such a multiscale 3D chemotaxis assay and reveal thatCaulobacter crescentuschemotaxis breaks with theEscherichia coliparadigm.
A full-length transcriptome dataset of normal andNosema ceranae-challenged midgut tissues of eastern honeybee workers
Authors: Du Yu , Fan Yuanchan , Chen Huazhi , Wang Jie , Xiong Cuiling , Zheng Yanzhen , Chen Dafu , Guo Rui
Published: March 2020

Apis cerana ceranais a subspecies of eastern honeybee,Apis cerana, and it plays a vital role in ecological maintenance in China. However,A. c. ceranais threatened by many pathogenic microorganisms includingNosema ceranae, a widespread fungal parasite that infected worldwide colonies. In this article, un-challenged (AcCK1, AcCK2) andN. ceranae-challenged midguts ofA. c. ceranaworkers (AcT1, AcT2) were sequenced utilizing Nanopore long-read sequencing technology. Totally, 11,727,628, 6,996,395, 14,383,735 and 11,580,154 raw reads were yielded from AcCK1, AcCK2, AcT1 and AcT2; the average lengths were 1147 bp, 908 bp, 992 bp and 1077 bp, and the average N50 were 1308 bp, 911 bp, 1079 bp and 1192 bp. The length distribution of was ranged 1 kb to more than 10 kb. Additionally, the quality (Q) score distribution of raw reads was among Q7~Q17. Further, 11,617,144, 6,940,895, 14,277,240 and 11,501,562 clean reads were respectively obtained from AcCK1, AcCK2, AcT1 and AcT2, and among them 78.40%, 82.50%, 79.05% and 80.20% were identified as full-length clean reads. In addition, full-length clean reads from AcCK1, AcT1, AcT2 and AcCK2 were ranged from 1 kb to more than 10 kb in length. Finally, the length distribution of redundant reads-removed full-length transcripts was among 1 kb~5 kb.

Value of the data

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This dataset enables better understanding the complexity ofA. c. ceranatranscriptome.

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Current dataset contributes to identification of genes and transcripts engaged in response of eastern honeybee toN. ceranaestress.

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The data provides a valuable genetic resource for deciphering alternative splicing and polyadenylation ofA. c. ceranamRNAs involved in host response toN. ceranaechallenge.

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The reported data is beneficial for uncovering the molecular mechanism regulating interaction between eastern honeybee and microsporidian.
In VivoEfficacy and PK/PD Modeling of KBP-7072, An Aminomethylcycline Antibiotic, in Neutropenic Pneumonia and Thigh Infection Models
Authors: Tan Xiaojuan , Zhang Min , Liu Qingmei , Wang Ping , Zhou Tian , Benn Vincent , Yang Fred
Published: March 2020

KBP-7072 is a novel aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative multidrug resistant bacterial isolates and strains.Antibacterial activity and the PK/PD relationship were assessed usingin vivoinfection models. Six to 8-week-old female CD-1 mice were randomized to oral KBP-7072, minocycline and vehicle in aKlebsiella pneumoniaemurine model, and KBP-7072, linezolid and vehicle for aStreptococcus pneumoniaemurine model. Each animal was inoculated withK. pneumoniaeorS. pneumoniaeplaced on the tip of the nares. KBP-7072 and antibiotics were started 3 hours post inoculation and continued for 3 days forK. pneumoniae, and were started 18 hours post inoculation and continued for 3 days forS. pneumoniae. Animals were euthanized at 0 (control group), 24, 48 or 72 hours post final dose.In vivoefficacy and PK/PD parameters were determined inStaphylococcus aureusisolate (6424MRSA-363),K. pneumoniaeisolate (6680kpn-522), andE. coliisolate (6691eco-558) murine thigh infection models.In vivoefficacy and PK/PD parameters (fAUC/MIC,fCmax/MIC and %T>MICfree) were calculated. Respiratory infection occurred in all inoculated mice. KBP-7072 produced a significant (p<0.05 to <0.001) dose-dependent decrease in colony forming units (CFUs) at all doses and a dose-dependent increase in survival rate (p<0.001 vs. vehicle). The median survival in all KBP-7072-treated groups was significantly greater vs. comparators (p<0.001). These results demonstrate potentin vivoefficacy for KBP-7072 and determined that the AUC/MIC parameter was optimal for assessing bacteriostatic and bactericidal effects of KBP-7072.