bluuebunny/crossref_metadata_2025 huggingface dataset:
Vocal production learning in the pale spear-nosed bat,
Phyllostomus discolor
Authors: Lattenkamp Ella Z. , Vernes Sonja C. , Wiegrebe Lutz
Published: April 2020

Vocal production learning (VPL), or the ability to modify vocalizations through the imitation of sounds, is a rare trait in the animal kingdom. While humans are exceptional vocal learners, few other mammalian species share this trait. Owing to their singular ecology and lifestyle, bats are highly specialized for the precise emission and reception of acoustic signals. This specialization makes them ideal candidates for the study of vocal learning, and several bat species have previously shown evidence supportive of vocal learning. Here we use a sophisticated automated set-up and a contingency training paradigm to explore the vocal learning capacity of pale spear-nosed bats. We show that these bats are capable of directional change of the fundamental frequency of their calls according to an auditory target. With this study, we further highlight the importance of bats for the study of vocal learning and provide evidence for the VPL capacity of the pale spear-nosed bat.
Structural colours reflect individual quality: a meta-analysis
Authors: White Thomas E.
Published: April 2020

Colourful ornaments often communicate salient information to mates, and theory predicts covariance between signal expression and individual quality. This has borne out among pigment-based signals, but the potential for ‘honesty’ in structural coloration is unresolved. Here, I synthesized the available evidence to test this prediction via meta-analysis and found that, overall, the expression of structurally coloured sexual signals is positively associated with individual quality. The effects varied by the measure of quality, however, with body condition and immune function reliably encoded across taxa, but not age nor parasite resistance. The relationship was apparent for both the colour and brightness of signals and was slightly stronger for iridescent ornaments. These results suggest diverse pathways to the encoding and exchange of information among structural colours while highlighting outstanding questions as to the development, visual ecology and evolution of this striking adornment.
A framework for second-order eigenvector centralities and clustering coefficients
Authors: Arrigo Francesca , Higham Desmond J. , Tudisco Francesco
Published: April 2020

We propose and analyse a general tensor-based framework for incorporating second-order features into network measures. This approach allows us to combine traditional pairwise links with information that records whether triples of nodes are involved in wedges or triangles. Our treatment covers classical spectral methods and recently proposed cases from the literature, but we also identify many interesting extensions. In particular, we define a mutually reinforcing (spectral) version of the classical clustering coefficient. The underlying object of study is a constrained nonlinear eigenvalue problem associated with a cubic tensor. Using recent results from nonlinear Perron–Frobenius theory, we establish existence and uniqueness under appropriate conditions, and show that the new spectral measures can be computed efficiently with a nonlinear power method. To illustrate the added value of the new formulation, we analyse the measures on a class of synthetic networks. We also give computational results on centrality and link prediction for real-world networks.
The Design of Lil’Flo, a Socially Assistive Robot for Upper Extremity Motor Assessment and Rehabilitation in the Community Via Telepresence
Authors: Sobrepera Michael J , Lee Vera G , Johnson Michelle J
Published: April 2020

Introduction

We present Lil’Flo, a socially assistive robotic telerehabilitation system for deployment in the community. As shortages in rehabilitation professionals increase, especially in rural areas, there is a growing need to deliver care in the communities where patients live, work, learn, and play. Traditional telepresence, while useful, fails to deliver the rich interactions and data needed for motor rehabilitation and assessment.

Methods

From prior work, we have developed design requirements for a socially assistive robot for upper extremity motor assessment and rehabilitation via telepresence. We designed Lil’Flo, targeted towards pediatric patients with cerebral palsy and brachial plexus injuries. The system combines traditional telepresence and computer vision with a humanoid, who can play games with patients and guide them in a present and engaging way under the supervision of a remote clinician.

Results

The humanoid’s arms have sufficient range of motion, and the face is able to communicate several emotions clearly. The system is portable, extensible, and cheaper than our prior iteration. A simple web interface allows operators to focus on interactions while the computer vision system stores data for analysis.

Conclusions

Lil’Flo represents a novel approach to delivering rehabilitation care in the community while maintaining the clinician-patient connection.
Impact of COVID-19 pandemic on severity of illness and resources required during intensive care in the greater New York City area
Authors: Badawi Omar , Liu Xinggang , Berman Iris , Amelung Pamela J , Doerfler Martin E. , Chandra Saurabh
Published: April 2020

Objective

Describe the changes in patient population, bed occupancy, severity of illness and ventilator requirements across a large health system in the greater New York City area during the pandemic response in comparison with the 2019 baseline.

Design

Observational, descriptive study of ICUs monitored by a tele-ICU system across Northwell Health. Inclusion criteria: All patients admitted to Northwell Health tele-ICUs during 2019 and between March 23, 2020 and April 6, 2020.

Exposure

A data extract was developed to collect data every hour for each ICU bed in the Northwell tele-critical care program as a quality reporting initiative to understand ICU capacity and resource utilization. A similar extract was developed for each hour of 2019.

Main Outcomes and Measures

Average of any given hour during the pre-COVID-19 and pandemic periods for the following metrics: proportion of beds occupied, proportion of ventilated patients, severity of illness (measured by the ICU Discharge Readiness Score (DRS)), and length of stay (LOS).

Results

Hourly analysis of data from 186 ICU beds from 14 ICUs and 9 hospitals were included, representing 10,714 patients in 2019 and 465 patients between March 23 and April 6, 2020. Average hourly occupancy increased from 64% to 78%, while the proportion of patients invasively ventilated increased from 33.9% to 84.2%. Median DRS (severity of illness score) increased from 1.08 (IQR: 0.24-6.98) to 39.38 (IQR: 12.00-71.28). Proportion of patients with Hispanic ethnicity doubled (7.8% to 16.6%; p<0.01) and proportion of female patients decreased from 46.3% to 32.9% (p<0.01).

Conclusions and Relevance

In addition to the expected increase in ICU occupancy and ventilator requirements, this large group of ICUs in midst of the COVID-19 epidemic are faced with managing a cohort of ICU patients with a dramatically higher severity of illness than their typical census.
Late immune-related adverse events in long-term responders to PD-1/PD-L1 checkpoint inhibitors: a multicentre study
Authors: Nigro Olga , Pinotti Graziella , De Galitiis Federica , Di Pietro Francesca Romana , Giusti Raffaele , Filetti Marco , Bersanelli Melissa , Lazzarin Alessandro , Bordi Paola , Catino Annamaria , Pizzutilo Pamela , Galetta Domenico , Marchetti Paolo , Botticelli Andrea , Scagnoli Simone , Russano Marco , Santini Daniele , Torniai Mariangela , Berardi Rossana , Ricciuti Biagio , De Giglio Andrea , Chiari Rita , Russo Alessandro , Adamo Vincenzo , Tudini Marianna , Silva Rosa Rita , Bolzacchini Elena , Giordano Monica , Di Marino Pietro , De Tursi Michele , Rijavec Erika , Ghidini Michele , Vallini Ilaria , Stucci Luigia Stefania , Tucci Marco , Pala Laura , Conforti Fabio , Queirolo Paola , Tanda Enrica , Spagnolo Francesco , Cecchi Federica , Bracarda Sergio , Macrini Serena , Santoni Matteo , Battelli Nicola , Fargnoli Maria Concetta , Porzio Giampiero , Tuzi Alessandro , Suter Matteo Basilio , Ficorella Corrado , Cortellini Alessio
Published: April 2020

Data on spectrum and grade of immune-related adverse events (irAEs) in long-term responders to immune checkpoint inhibitors (ICI) are lacking.

We performed a retrospective multicenter study to characterized irAEs occurring after a 12-months minimum treatment period with PD-(L)1 ICIs in advanced cancer patients. IrAEs were categorized into “early” (≤12 months) and “late” (>12 months).

From September 2013 to October 2019, 436 consecutive patients were evaluated. 223 experienced any grade early-irAEs (51.1%), while 132 experienced any grade late-irAEs (30.3%) (p < 0.0001). Among the latter, 29 (22%) experienced a recurrence of an early-irAEs, while 103 (78%) experienced de novo late-irAEs involving different system/organ. Among patients with late-irAEs, 21 experienced G3/G4 irAEs (4.8%). Median time to onset of early-irAEs was 3.4 months (95%CI: 2.8-4.2), while the median time to onset of late-irAEs was 16.6 months (95%CI: 15.8-17.6). Cumulative time-adjusted risk of disease progression according to both the early-irAEs (HR = 0.63 [95%CI: 0.30-1.29], p = 0.204) and late-irAEs occurrence revealed no statistically significant differences (HR = 0.75 [95%CI: 0.37-1.56], p = 0.452). Also the time-adjusted cumulative risk of death according to both early-irAEs (HR = 0.79 [95%CI: 0.34-1.86], p = 0.598) and late-irAEs (HR = 0.92 [95%CI: 0.49-1.74], p = 0.811) did not show statistically significant differences.

Although less frequent than early-irAEs, late-irAEs are quite common in long responders to PD-(L)1 ICIs, and are different in terms of spectrum and grade. Time-adjusted analysis revealed that the cumulative risk of disease progression and death were not significantly reduced in patients who experienced late-irAEs.
Excess cases of influenza suggest an earlier start to the coronavirus epidemic in Spain than official figures tell us: an analysis of primary care electronic medical records from over 6 million people from Catalonia
Authors: Coma Ermengol , Mora Nuria , Prats-Uribe Albert , Fina Francesc , Prieto-Alhambra Daniel , Medina-Peralta Manuel
Published: April 2020

Objectives

There is uncertainty about when the first cases of COVID-19 appeared in Spain, as asymptomatic patients can transmit the virus. We aimed to determine whether influenza diagnoses masked early COVID-19 cases and, if so, estimate numbers of undetected COVID-19 cases in a large database of primary-care records covering >6 million people in Catalonia.

Design

Time-series study of influenza and COVID-19 cases, using all influenza seasons from autumn-winter 2010-2011 to autumn-winter 2019-2020.

Setting

Primary care, Catalonia, Spain.

Participants

People registered in one of the contributing primary-care practices, covering >6 million people and >85% of the population.

Main outcome measures

Weekly new cases of influenza and COVID-19 diagnosed in primary care.

Analyses

Daily counts of both cases were computed using the total cases recorded over the previous 7 days to avoid weekly effects on recording practice. Epidemic curves were characterised for the 2010-2011 to 2019-2020 influenza seasons. Influenza seasons with a similar epidemic curve and peak case number as the 2019-2020 season were used to model predictions for 2019-2020. ARIMA models were fitted to the included influenza seasons, overall and stratified by age, to estimate expected case numbers. Daily excess influenza cases were defined as the number of observed minus expected cases.

Results

Four influenza season curves (2011-2012, 2012-2013, 2013-2014, and 2016-2017) were used to estimate the number of expected cases of influenza in 2019-2020. Between 4 February 2020 and 20 March 20202, 8,017 (95% CI: 1,841 to 14,718) excess influenza cases were identified. This excess was highest in the 15-64 age group.

Conclusions

COVID-19 cases may have been present in the Catalan population when the first imported case was reported on 25 February 2020. COVID-19 carriers may have been misclassified as influenza diagnoses in primary care, boosting community transmission before public health measures were taken. In future, the surveillance of excess influenza cases using widely available primary-care electronic medical records could help detect new outbreaks of COVID-19 or other influenza-like illness-causing pathogens. Earlier detection would allow public health responses to be initiated earlier than during the current crisis.
Scaling diagnostics in times of COVID-19: Colorimetric Loop-mediated Isothermal Amplification (LAMP) assisted by a 3D-printed incubator for cost-effective and scalable detection of SARS-CoV-2
Authors: González-González Everardo , Lara-Mayorga Itzel Montserrat , Rodríguez-Sánchez Iram Pablo , León Felipe Yee-de , García-Rubio Andrés , Garciaméndez-Mijares Carlos Ezio , Guerra-Alvarez Gilberto Emilio , García-Martínez Germán , Aguayo-Hernández Juan Andrés , Márquez-García Eduardo , Zhang Yu Shrike , Martínez-Chapa Sergio O. , Zúñiga Joaquín , Santiago Grissel Trujillo-de , Alvarez Mario Moisés
Published: April 2020

By the third week of June 2020, more than 8,500,000 positive cases of COVID-19 and more than 450,000 deaths had been officially reported worldwide. The COVID-19 pandemic arrived in Latin America, India, and Africa—territories in which the mounted infrastructure for diagnosis is greatly underdeveloped. Here, we demonstrate the combined use of a three-dimensional (3D)-printed incubation chamber for commercial Eppendorf PCR tubes, and a colorimetric embodiment of a loop-mediated isothermal amplification (LAMP) reaction scheme for the detection of SARS-CoV-2 nucleic acids. We used this strategy to detect and amplify SARS-CoV-2 genetic sequences using a set of in-house designed initiators that target regions encoding the N protein. We were able to detect and amplify SARS-CoV-2 nucleic acids in the range of 62 to 2 × 105 DNA copies by this straightforward method. Using synthetic SARS-CoV-2 samples and a limited number of RNA extracts from patients, we also demonstrate that colorimetric LAMP is a quantitative method comparable in diagnostic performance to RT-qPCR. We envision that LAMP may greatly enhance the capabilities for COVID-19 testing in situations where RT-qPCR is not feasible or is unavailable. Moreover, the portability, ease of use, and reproducibility of this strategy make it a reliable alternative for deployment of point-of-care SARS-CoV-2 detection efforts during the pandemics.
Epidemic prevention and control measures in China significantly curbed the epidemic of COVID-19 and influenza
Authors: Kong Xiang-Sha , Liu Feng , Wang Hai-Bo , Yang Rui-Feng , Chen Dong-Bo , Wang Xiao-Xiao , Lu Feng-Min , Rao Hui-Ying , Chen Hong-Song
Published: April 2020

At the end of 2019, an outbreak of unknown pathogen pneumonia occurred in China, then it was named corona virus disease 2019 (COVID-19). With the rapid spread of COVID-19, a series of strict prevention and control measures were implemented to cut the spread of the epidemic. Influenza as a respiratory tract infection disease as COVID-19 might also be controlled. To assess the effects, we used the total passenger numbers sent in mainland China from 2018 to 2020 and the daily number of railway passenger (DNRP) flow in 2020 during Spring Festival travel rush to reflect the population movement and further to analyze newly and cumulative confirmed COVID-19 and influenza. We found that with implementing the series measures on COVID-19, not only COVID-19, but also influenza mitigated in China. The prevention and control measures for COVID-19 might be used in controlling respiratory tract diseases, and reducing the national health economic burden. When other countries issue measures on COVID-19 and influenza, they should consider adopting more aggressive epidemic prevention and control strategies.
Stability of the COVID-19 virus under wet, dry and acidic conditions
Authors: Sun Zhi-ping , Cai Xia , Gu Chen-jian , Zhang Rong , Han Wen-dong , Qian Yun , Wang Yu-yan , Xu Wei , Wu Yang , Cheng Xunjia , Yuan Zheng-hong , Xie You-hua , Qu Di
Published: April 2020

COVID-19 has become a pandemic and is spreading fast worldwide. The COVID-19 virus is transmitted mainly through respiratory droplets and close contact. However, the fecal-oral transmission of the virus has not been ruled out and it is important to ascertain how acidic condition in the stomach affects the infectivity of the virus. Besides, it is unclear how stable the COVID-19 virus is under dry and wet conditions. In the present study, we have shown that the COVID-19 virus is extremely infectious as manifested by the infection of Vero-E6 cells by one PFU (Plaque Forming Unit) of the virus. We then investigated the stability of the COVID-19 virus in wet, dry and acidic (pH2.2) environments at room temperature. Results showed that the COVID-19 virus could survive for three days in wet and dry environments, but the dry condition is less favorable for the survival of the virus. Our study also demonstrated that the COVID-19 virus at a relative high titer (1.2 x 103 PFU) exhibits a certain degree of tolerance to acidic environment at least for 60 minutes. When the virus titer was ≤1.0 x 103 PFU, acid treatment (pH2.2) for 30 or 60 minute resulted in virus inactivation. It suggests that the virus at a high concentration may survive in the acidic environment of the stomach. The finding of the present study will contribute to the control of the spread of the COVID-19 virus.
COVID-19 pandemic in the African continent: Forecasts of cumulative cases, new infections, and mortality
Authors: Achoki T , Alam U , Were L , Gebremedhin T , Senkubuge F , Lesego A , Liu S , Wamai R , Kinfu Y
Published: April 2020

Background

The epidemiology of COVID-19 remains speculative in Africa. To the best of our knowledge, no study, using robust methodology provides its trajectory for the region or accounts for local context. This paper is the first systematic attempt to provide prevalence, incidence, and mortality estimates across Africa.

Methods

Caseloads and incidence forecasts are from a co-variate-based instrumental variable regression model. Fatality rates from Italy and China were applied to generate mortality estimates after making relevant health system and population-level characteristics related adjustments between each of the African countries.

Results

By June 30 2020, around 16.3 million people in Africa will contract COVID-19 (95% CI 718,403 to 98,358,799). Northern and Eastern Africa will be the most and least affected areas. Cumulative cases by June 30 are expected to reach around 2.9 million (95% CI 465,028 to 18,286,358) in Southern Africa, 2.8 million (95% CI 517,489 to 15,056,314) in Western Africa, and 1.2 million (95% CI 229,111 to 6,138,692) in Central Africa. Incidence for the month of April 2020 is expected to be highest in Djibouti, 32.8 per 1000 (95% CI 6.25 to 171.77), while Morocco will experience among the highest fatalities (1,045 deaths, 95% CI 167 to 6,547).

Conclusion

Less urbanized countries with low levels of socio-economic development (hence least connected to the world), are likely to register lower and slower transmissions at the early stages of an epidemic. However, the same enabling factors that worked for their benefit can hinder interventions that have lessened the impact of COVID-19 elsewhere.
Myocyte Specific Upregulation of ACE2 in Cardiovascular Disease: Implications for SARS-CoV-2 mediated myocarditis
Authors: Tucker Nathan R. , Chaffin Mark , Bedi Kenneth C. , Papangeli Irinna , Akkad Amer-Denis , Arduini Alessandro , Hayat Sikander , Eraslan Gökcen , Muus Christoph , Bhattacharyya Roby , Stegmann Christian M. ,   Human Cell Atlas Lung Biological Network, Margulies Kenneth B. , Ellinor Patrick T.
Published: April 2020

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by a novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 infection of host cells occurs predominantly via binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor.1 Hypertension and pre-existing cardiovascular disease are risk factors for morbidity from COVID-19,2 and it remains uncertain whether the use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) impacts infection and disease. Here, we aim to shed light on this question by assessing ACE2 expression in normal and diseased human myocardial samples profiled by bulk and single nucleus RNA-seq.
Estimating Probabilities of Success of Clinical Trials for Vaccines and Other Anti-Infective Therapeutics
Authors: Wong Chi Heem , Siah Kien Wei , Lo Andrew W.
Published: April 2020

A key driver in biopharmaceutical investment decisions is the probability of success of a drug development program. We estimate the probabilities of success (PoS) of clinical trials for vaccines and other anti-infective therapeutics using 43,414 unique triplets of clinical trial, drug, and disease between January 1, 2000, and January 7, 2020, yielding 2,544 vaccine programs and 6,829 non-vaccine programs targeting infectious diseases. The overall estimated PoS for an industry-sponsored vaccine program is 39.6%, and 16.3% for an industry-sponsored anti-infective therapeutic. Among industry-sponsored vaccines programs, only 12 out of 27 disease categories have seen at least one approval, with the most successful being against monkeypox (100%), rotavirus (78.7%), and Japanese encephalitis (67.6%). The three infectious diseases with the highest PoS for industry-sponsored non-vaccine therapeutics are smallpox (100%), CMV (31.8%), and onychomycosis (29.8%). Non-industry-sponsored vaccine and non-vaccine development programs have lower overall PoSs: 6.8% and 8.2%, respectively. Viruses involved in recent outbreaks—MERS, SARS, Ebola, Zika—have had a combined total of only 45 non-vaccine development programs initiated over the past two decades, and no approved therapy to date (Note: our data was obtained just before the COVID-19 outbreak and do not contain information about the programs targeting this disease.) These estimates offer guidance both to biopharma investors as well as to policymakers seeking to identify areas most likely to be undeserved by private-sector engagement and in need of public-sector support.
Protein Classifier for Thyroid Nodules Learned from Rapidly Acquired Proteotypes
Authors: Sun Yaoting , Selvarajan Sathiyamoorthy , Zang Zelin , Liu Wei , Zhu Yi , Zhang Hao , Chen Hao , Cai Xue , Gao Huanhuan , Wu Zhicheng , Chen Lirong , Teng Xiaodong , Zhao Yongfu , Mantoo Sangeeta , Lim Tony Kiat-Hon , Hariraman Bhuvaneswari , Yeow Serene , bin Syed Abdillah Syed Muhammad Fahmy , Lee Sze Sing , Ruan Guan , Zhang Qiushi , Zhu Tiansheng , Wang Weibin , Wang Guangzhi , Xiao Junhong , He Yi , Wang Zhihong , Sun Wei , Qin Yuan , Xiao Qi , Zheng Xu , Wang Linyan , Zheng Xi , Xu Kailun , Shao Yingkuan , Liu Kexin , Zheng Shu , Aebersold Ruedi , Li Stan Z. , Kon Oi Lian , Iyer N. Gopalakrishna , Guo Tiannan
Published: April 2020

Up to 30% of thyroid nodules cannot be accurately classified as benign or malignant by cytopathology. Diagnostic accuracy can be improved by nucleic acid-based testing, yet a sizeable number of diagnostic thyroidectomies remains unavoidable. In order to develop a protein classifier for thyroid nodules, we analyzed the quantitative proteomes of 1,725 retrospective thyroid tissue samples from 578 patients using pressure-cycling technology and data-independent acquisition mass spectrometry. With artificial neural networks, a classifier of 14 proteins achieved over 93% accuracy in classifying malignant thyroid nodules. This classifier was validated in retrospective samples of 271 patients (91% accuracy), and prospective samples of 62 patients (88% accuracy) from four independent centers. These rapidly acquired proteotypes and artificial neural networks supported the establishment of an effective protein classifier for classifying thyroid nodules.
A Scalable Method of Applying Heat and Humidity for Decontamination of N95 Respirators During the COVID-19 Crisis
Authors: Anderegg Loïc , Meisenhelder Cole , Ngooi Chiu Oan , Liao Lei , Xiao Wang , Chu Steven , Cui Yi , Doyle John M.
Published: April 2020

A lack of N95 respirators during the COVID-19 crisis has placed healthcare workers at risk. It is important for any N95 reuse strategy to determine the effects that proposed protocols would have on the physical functioning of the mask, as well as the practical aspects of implementation. Here we propose and implement a method of heating N95 respirators with moisture (85 °C, 60-85% humidity). We test both mask filtration efficiency and fit to validate this process. Our tests focus on the 3M 1860, 3M 1870, and 3M 8210 Plus N95 models. After five cycles of the heating procedure, all three respirators pass both quantitative fit testing (score of >100) and show no degradation of mask filtration efficiency. We also test the Chen Heng V9501 KN95 and HKYQ N95 finding no degradation of mask filtration efficiency, however even for unheated masks these scored <50 for every fit test. The heating method presented here is scalable from individual masks to over a thousand a day with a single industrial convection oven, making this method practical for local application inside health-care facilities.
Phylogeography and Resistome Epidemiology of Gram-Negative Bacteria in Africa: A Systematic Review and Genomic Meta-Analysis from a One-Health Perspective
Authors: Sekyere John Osei , Reta Melese Abate
Published: April 2020

Objectives/Backgrounds

Antibiotic resistance (ABR) remains a major threat to public health and infectious disease management globally. However, ABR ramifications in developing countries is worsened by limited molecular diagnostics, expensive therapeutics, inadequate skilled clinicians and scientists, and unsanitary environments.

Methods

Data on specimens, species, clones, resistance genes, mobile genetic elements, and diagnostics were extracted and analysed from English articles published between 2015 and December 2019. The genomes and resistomes of the various species, obtained from PATRIC and NCBI, were analysed phylogenetically using RAxML and annotated with Figtree. The phylogeography of resistant clones/clades was mapped manually.

Results & conclusion

Thirty species from 31 countries and 24 genera from 41 countries were respectively analysed from 146 articles and 3028 genomes. Genes mediating resistance to β-lactams (including blaTEM-1, blaCTX-M, blaNDM, blaIMP, blaVIM, blaOXA-48/181), fluoroquinolones (oqxAB, qnrA/B/D/S, gyrA/B and parCE mutations etc.), aminoglycosides (including armA, rmtC/F), sulphonamides (sul-1/2/3), trimethoprim (dfrA), tetracycline (tet(A/B/C/D/G/O/M/39)), colistin (mcr-1), phenicols (catA/B, cmlA), and fosfomycin (fosA) were mostly found in Enterobacter spp. and K. pneumoniae, and also in Serratia marcescens, Escherichia coli, Salmonella enterica, Pseudomonas, Acinetobacter baumannii, etc. on mostly IncF-type, IncX3/4, ColRNAI, and IncR plasmids, within IntI1 gene cassettes, insertion sequences and transposons. Clonal and multiclonal outbreaks and dissemination of resistance genes across species, countries and between humans, animals, plants and the environment were observed; E. coli ST103, K. pneumoniae ST101, S. enterica ST1/2 and V. cholerae ST69/515 were common strains. Most pathogens were of human origin and zoonotic transmissions were relatively limited. One Health studies in Africa are needed.

Highlights/Significance

Antibiotic resistance (AR) is one of the major public health threats and challenges to effective containment and treatment of infectious bacterial diseases worldwide. Herein, we used different methods to map out the geographical hotspots, sources and evolutionary epidemiology of AR. Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Acinetobacter baumanii, Pseudomonas aeruginosa, Enterobacter spp., Neisseria meningitis/gonnorhoeae, Vibrio cholerae, Campylobacter jejuni etc. were common pathogens shuttling AR genes. Transmission of same clones/strains across countries and between animals, humans, plants and the environment were observed. We recommend Enterobacter spp. or K. pneumoniae as better model/index organisms for AR surveillance.
Estimating cost-benefit of quarantine length for COVID-19 mitigation
Authors: Eilersen Andreas , Sneppen Kim
Published: April 2020

The international community has been put in an unprecedented situation by the COVID-19 pandemic. Creating models to describe and quantify alternative mitigation strategies becomes increasingly urgent. In this study, we propose an agent-based model of disease transmission in a society divided into closely connected families, workplaces, and social groups. This allows us to discuss mitigation strategies, including targeted quarantine measures. We find that workplace and more diffuse social contacts are roughly equally important to disease spread, and that an effective lockdown must target both. We examine the cost-benefit of replacing a lockdown with tracing and quarantining contacts of the infected. Quarantine can contribute substantially to mitigation, even if it has short duration and is done within households. When reopening society, testing and quarantining is a strategy that is much cheaper in terms of lost workdays than a long lockdown of workplaces. A targeted quarantine strategy is quite efficient with only 5 days of quarantine, and its effect increases when testing is more widespread.
Recovery Ratios Reliably Anticipate COVID-19 Pandemic Progression
Authors: Nicolau Dan V. , Hasson Alexander , Bafadhel Mona
Published: April 2020

The COVID-19 pandemic is placing unprecedented demands on healthcare systems worldwide and exacting a massive humanitarian toll. This makes the development of accurate predictive models imperative, not just for understanding the course of the pandemic but more importantly for gaining insight into the efficacy of public health measures and planning accordingly. Epidemiological models are forced to make assumptions about many unknowns and therefore can be unreliable. Here, taking an empirical approach, we report a 20-30 day lag between the peak of confirmed to recovered cases and the peak of daily deaths in each country, independent of the epoch of that country in its pandemic cycle. This analysis is expected to be largely independent of the proportion of the population being tested and therefore should aid in planning around the timing and easing of public health measures. Our data also suggests broad predictions for the number of fatalities, generally somewhat lower than most other models. Finally, our model suggests that the world as a whole is shortly to enter a recovery phase, at least as far as the first pandemic wave is concerned.
Improvement in Sleep Duration was Associated with Higher Cognitive Function among Middle-Aged and Elderly Chinese Participants
Authors: Hua Jianian , Sun Hongpeng , She Yueping
Published: April 2020

Study objectives

Rodent studies suggested that improvement in sleep duration might correlate with better cognitive function. We aimed to examine the associations between changes in sleep duration and cognitive function.

Methods

10325 individuals from the China Health and Retirement Longitudinal Study (CHARLS) were included. Self-reported nocturnal sleep duration and cognitive function were assessed in CHARLS 2011, 2013 and 2015 (Wave 1, Wave 2, Wave3). Cognitive function was assessed by a global cognition score, which included three domains: episodic memory, figure drawing and Telephone Interview of Cognitive Status (TICS). Generalized additive models (GAM) and Generalized estimation equations (GEE) were used to examine the associations between baseline sleep duration and longitudinal cognitive function. We used generalized linear models (GLM) to study the associations between changes in sleep duration and cognitive function in Wave 3.

Results

After adjusting for potential confounders, change from short sleep duration (SSD) to moderate sleep duration (MSD) was associated with better global cognition scores (β=0.54, P <0.01). Change from SSD to long sleep duration (LSD) (β=-0.94, P <0.001) or change from LSD to SSD (β=-1.38, P <0.01) was associated with lower global cognition. For individuals with MSD, ≥2 h increase (β=-0.89, P <0.001) or decrease (β=-0.70, P <0.001) in sleep duration was associated with lower global cognition.

Conclusions

For short sleepers, improvement in sleep duration correlated with better cognition. For long sleepers, there was no need to reduce sleep duration. Excessive changes or deviation from the moderate duration was associated with lower cognition.
Scirpy: A Scanpy extension for analyzing single-cell T-cell receptor sequencing data
Authors: Sturm Gregor , Szabo Tamas , Fotakis Georgios , Haider Marlene , Rieder Dietmar , Trajanoski Zlatko , Finotello Francesca
Published: April 2020

Advances in single-cell technologies have enabled the investigation of T cell phenotypes and repertoires at unprecedented resolution and scale. Bioinformatic methods for the efficient analysis of these large-scale datasets are instrumental for advancing our understanding of adaptive immune responses in cancer, but also in infectious diseases like COVID-19. However, while well-established solutions are accessible for the processing of single-cell transcriptomes, no streamlined pipelines are available for the comprehensive characterization of T cell receptors. Here we proposeScirpy, a scalable Python toolkit that provides simplified access to the analysis and visualization of immune repertoires from single cells and seamless integration with transcriptomic data.

Availability and implementation

Scirpysource code and documentation are available athttps://github.com/icbi-lab/scirpy.
Analysing recovery from pandemics by Learning Theory: the case of CoVid-19
Authors: Duffey Romney B , Zio Enrico
Published: April 2020

We present a method for predicting the recovery time from infectious diseases outbreaks such as the recent CoVid-19 virus. The approach is based on the theory of learning from errors, specifically adapted to the control of the virus spread by reducing infection rates using countermeasures such as medical treatment, isolation, social distancing etc. When these are effective, the infection rate, after reaching a peak, declines following a given recovery rate curve. We use presently available data from China, South Korea and others to make actual predictions of the time needed for securing minimum infection rates in the future.
Twitter and Pain: An Observational Analysis of Pain-Related Tweets in Ireland
Authors: Mullins Cormac , O’Carroll Robert ffrench , Lane Justin , O’Connor Therese
Published: April 2020

Introduction

Studies involving Twitter and chronic pain can provide highly valuable patient-generated information. The aim of this paper was to examine pain-related tweets in Ireland over a two-week period 22nd June 2017-5th July 2017 using pain-related keywords. We wished to identify demographic details regarding the Twitter users; most common topics discussed; sentiment analysis; and reach of tweets

Methods

A third-party data analytics company used 24 pain-related keywords over a 14-day period between the dates 22nd June – 5th July 2017.

Results

There were 941 tweets identified during the study from 715 contributors. These reached 2.62 million accounts and generated 2.88 million impressions. The most frequently occurring keywords were headache (n=321); migraine (n=147); back pain (n=123); cannabis (n=114); and chronic pain (n=85). There were 1.94 times as many tweets from females as males. The highest proportion of tweets from female users was in the fibromyalgia (83%) and migraine (60%) categories, and from males in the sciatica (35%), chronic pain (34%) and back pain (32%) categories. Cannabis-related tweets reflected mostly non-personal content (90%), with a highly positive sentiment, and the highest reach per tweet. The largest amount of advice was offered in the back pain category. Retweets were more likely to reflect a positive sentiment.

Conclusion

A substantial discussion of pain-related topics took place on Twitter during our study period. This provided real-time, dynamic information from individuals on discussion topics in pain medicine. This can be used to gain a greater understanding of the pain experience. As patients are increasingly acquiring healthcare information through online sources, high quality information from approved sources should be promoted on such platforms.
Global convergence of COVID-19 basic reproduction number and estimation from early-time SIR dynamics
Authors: Katul Gabriel G. , Mrad Assaad , Bonetti Sara , Manoli Gabriele , Parolari Anthony J.
Published: April 2020

The SIR (‘susceptible-infectious-recovered’) formulation is used to uncover the generic spread mechanisms observed by COVID-19 dynamics globally, especially in the early phases of infectious spread. During this early period, potential controls were not effectively put in place or enforced in many countries. Hence, the early phases of COVID-19 spread in countries where controls were weak offer a unique perspective on the ensemble-behavior of COVID-19 basic reproduction number Ro. The work here shows that there is global convergence (i.e. across many nations) to an uncontrolled Ro = 4.5 that describes the early time spread of COVID-19. This value is in agreement with independent estimates from other sources reviewed here and adds to the growing consensus that the early estimate of Ro = 2.2 adopted by the World Health Organization is low. A reconciliation between power-law and exponential growth predictions is also featured within the confines of the SIR formulation. Implications for evaluating potential control strategies from this uncontrolled Ro are briefly discussed in the context of the maximum possible infected fraction of the population (needed for assessing health care capacity) and mortality (especially in the USA given diverging projections). Model results indicate that if intervention measures still result in Ro> 2.7 within 49 days after first infection, intervention is unlikely to be effective in general for COVID-19. Current optimistic projections place mortality figures in the USA in the range of 100,000 fatalities. For fatalities to be confined to 100,000 requires a reduction in Ro from 4.5 to 2.7 within 17 days of first infection assuming a mortality rate of 3.4%.
Optimal Control applied to a SEIR model of 2019-nCoV with social distancing
Authors: Mallela Abhishek
Published: April 2020

Does the implementation of social distancing measures have merit in controlling the spread of the novel coronavirus? In this study, we develop a mathematical model to explore the effects of social distancing on new disease infections. Mathematical analyses of our model indicate that successful eradication of the disease is strongly dependent on the chosen preventive measure. Numerical computations of the model solution demonstrate that the ability to flatten the curve becomes easier as social distancing is strictly enforced. Based on our model, we also formulate an optimal control problem and solve it using Pontryagin’s Maximum Principle and an efficient numerical iterative method. Our numerical results of an optimal 2019-nCoV treatment protocol that yields a minimum disease burden from this disease indicates that social distancing is vitally important.
Fine-scale heterogeneity in Schistosoma mansoni force of infection measured through antibody response
Authors: Arnold Benjamin F. , Kanyi Henry , Njenga Sammy M. , Rawago Fredrick O. , Priest Jeffrey W. , Secor W. Evan , Lammie Patrick J. , Won Kimberly Y. , Odiere Maurice R.
Published: April 2020

Identifying populations with active transmission and monitoring changes in transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected in stool using microscopy, which is logistically difficult at program scale and has low sensitivity when people have low infection burdens. We compared serological measures of transmission based on antibody response to schistosomiasis soluble egg antigen (SEA) with stool-based measures of infection among 3,663 preschool-age children in an area endemic for S. mansoni in western Kenya. Serological measures of transmission closely aligned with stool-based measures of infection, and serological measures provided better resolution for between-community differences at lower levels of infection. Serology enabled fine- scale measures of heterogeneity in force of infection both geographically and by age. Our results show that serologic surveillance platforms represent an important new opportunity to guide and monitor schistosomiasis control programs.
A separable neural code in monkey IT enables perfect CAPTCHA decoding
Authors: Katti Harish , Arun S. P.
Published: April 2020

Reading distorted letters is easy for us but so challenging for machine vision that it is used on websites as CAPTCHAs (Completely Automated Public Turing test to tell Computers and Humans Apart). How does our brain solve this problem? One solution is to have neurons invariant to letter distortions but selective for letter combinations. Another is for neurons to separately encode letter distortions and combinations. Here, we provide evidence for the latter using neural recordings in the monkey inferior temporal (IT) cortex. Neurons encoded letter distortions as a product of letter and distortion tuning, and letter combinations as a sum of letters. These rules were sufficient for perfect CAPTCHA decoding and were also present in neural networks trained for word recognition. Taken together, our findings suggest that a separable neural code enables efficient letter recognition.
Cas9-generated auxotrophs ofPhaeodactylum tricornutumare characterized by small and large deletions that can be complemented by plasmid-based genes
Authors: Slattery Samuel S. , Wang Helen , Giguere Daniel J. , Kocsis Csanad , Urquhart Bradley L. , Karas Bogumil J. , Edgell David R.
Published: April 2020

The model diatomPhaeodactylum tricornutumis an attractive candidate for synthetic biology applications. Development of auxotrophic strains ofP. tricornutumwould provide alternative selective markers to commonly used antibiotic resistance genes. Here, using CRISPR/Cas9, we show successful editing of genes in the uracil, histidine, and tryptophan biosynthetic pathways. Editing events are characterized by loss of heterozygosity and by the occurrence of large deletions of up to ~2.7-kb centred on the editing site. The uracil and histidine-requiring phenotypes can be complemented by plasmid-based copies of the intact genes after curing of the Cas9-editing plasmid. Growth of uracil auxotrophs on media supplemented with 5-FOA and uracil results in loss of the complementing plasmid, providing a facile method for plasmid curing with potential applications in strain engineering and CRISPR editing. Metabolomic characterization of uracil auxotrophs revealed changes in cellular orotate concentrations consistent with partial or complete loss of orotate phosphoribosyl transferase activity in knockout strains. Our results expand the range ofP. tricornutumauxotrophic strains and demonstrate that auxotrophic complementation markers provide a viable alternative to traditionally used antibiotic selection markers. Plasmid-based auxotrophic markers should expand the range of genome engineering applications and provide a means for biocontainment of engineeredP. tricornutumstrains.
Deletion of immune evasion genes provides an effective vaccine design for tumor-associated herpesviruses
Authors: Brar Gurpreet , Farhat Nisar A. , Sukhina Alisa , Lam Alex K. , Kim Yong Hoon , Hsu Tiffany , Tong Leming , Lin Wai Wai , Ware Carl F. , Blackman Marcia A. , Sun Ren , Wu Ting-Ting
Published: April 2020

Vaccines based on live attenuated viruses often induce broad, multifaceted immune responses. However, they also usually sacrifice immunogenicity for attenuation. It is particularly difficult to elicit an effective vaccine for herpesviruses due to an armament of immune evasion genes and a latent phase. Here, to overcome the limitation of attenuation, we developed a rational herpesvirus vaccine in which viral immune evasion genes were deleted to enhance immunogenicity while also attaining safety. To test this vaccine strategy, we utilized murine gammaherpesvirus-68 (MHV-68) as a proof-of-concept model for the cancer-associated human γ-herpesviruses, Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus. We engineered a recombinant MHV-68 virus by targeted inactivation of viral antagonists of type I interferon (IFN-I) pathway and deletion of the latency locus responsible for persistent infection. This recombinant virus is highly attenuated with no measurable capacity for replication, latency, or persistence in immunocompetent hosts. It stimulates robust innate immunity, differentiates virus-specific memory T cells, and elicits neutralizing antibodies. A single vaccination affords durable protection that blocks the establishment of latency following challenge with the wild type MHV-68 for at least six months post-vaccination. These results provide a novel approach to effective vaccination against cancer-associated herpesviruses through the elimination of latency and key immune evasion mechanisms from the pathogen.
Doxycycline Significantly Enhances Induction of iPSCs to Endoderm by Enhancing survival via AKT Phosphorylation
Authors: Esteva-Font Cristina , Su Tao , Peaslee Caitlin , Duwaerts Caroline , Liu Ke , Medina Marisa , Maher Jacquelyn J. , Mattis Aras N.
Published: April 2020

Induced pluripotent stem cells (iPSCs) provide an important tool for the generation patient-derived cells including hepatocyte-like cells via developmental cues through an endoderm intermediate. However, most iPSCs fail to differentiate into endoderm, with induction resulting in apoptosis. To address this issue, we built upon published methods to develop an improved protocol with our discovery that doxycycline dramatically enhances the iPSC to endoderm differentiation efficiency by inhibiting apoptosis and promoting proliferation via the AKT pathway. We tested this new protocol in more than 70 iPSC lines with consistent formation of complete sheets of endoderm in 90%. Endoderm generated by our method achieves similar transcriptomic profiles, including FOXA2, HNF1β, CXCR4, and SOX17 positive cells, and the ability to be further differentiated. Furthermore this method achieves a four-fold increase in endoderm cell number and will accelerate studies of human diseasesin vitroand facilitate the expansion of iPSC-derived cells for transplantation studies.
Single nucleus sequencing fails to detect microglial activation in human tissue
Authors: Thrupp N. , Frigerio C. Sala , Wolfs L. , Skene N. G. , Poovathingal S. , Fourne Y. , Matthews P. M. , Theys T. , Mancuso R. , de Strooper B. , Fiers M.
Published: April 2020

Single nucleus RNA-Seq (snRNA-Seq) methods are used as an alternative to single cell RNA-Seq methods, as they allow transcriptomic profiling of frozen tissue. However, it is unclear whether snRNA-Seq is able to detect cellular state in human tissue. Indeed, snRNA-Seq analyses of human brain samples have failed to detect a consistent microglial activation signature in Alzheimer’s Disease. A comparison of microglia from single cells and single nuclei of four human subjects reveals that ~1% of genes is depleted in nuclei compared to whole cells. This small population contains 18% of genes previously implicated in microglial activation, includingAPOE, CST3, FTL, SPP1, andCD74. We confirm our findings across multiple previous single nucleus and single cell studies. Given the low sensitivity of snRNA-Seq to this population of activation genes, we conclude that snRNA-Seq is not suited to detecting cellular activation in microglia in human disease.