bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroendocrine Carcinomas of the Gallbladder
Authors: Lee Sun Mi , Sung Chang Ohk
Published: August 2020

Neuroendocrine carcinoma (NEC) is an aggressive malignant tumor that rarely arises from the gallbladder. Here, we investigated the clinicopathologic and immunohistochemical characteristics of 34 NECs of the gallbladder. The patients were predominantly women (68%) with a median age of 63 years (range, 37 to 82 y). NECs frequently occurred in the fundus (44%) as mass-forming lesions (66%). Histologically, 17 tumors were of small cell type, and another 17 were of large cell type. Twenty-three cases (68%) were associated with biliary intraepithelial neoplasia (38%) and intracholecystic papillary neoplasm (29%). The majority of tumors exhibited a diffuse growth pattern (74%), followed by organoid (24%) or scirrhous (2%) growth patterns. Histologic features related to neuroendocrine differentiation, such as nuclear molding (56%), perilobular pseudopalisading (18%), and rosette formation (15%), were identified. Immunohistochemically, cytokeratin 7 and 20 were expressed in 19 (56%) and 8 (24%) cases, respectively. Loss of Rb1 expression and concomitant overexpression of p16 were observed in 25 (74%) cases. No BRAFV600E mutations were identified in any of the 34 NECs. For survival analysis, the 1-, 3-, and 5-year overall survival rates were 64%, 35%, and 19%, respectively. In a multivariate analysis, the receipt of adjuvant chemoradiation therapy was identified as the only independent prognostic factor associated with the overall survival rate. The 1- and 3-year overall survival rates of patients with NECs were poorer for patients with poorly differentiated adenocarcinoma of the gallbladder (P<0.001). The complete resection and application of postoperative adjuvant therapy may influence a better clinical outcome in patients with NEC of the gallbladder.
Reducing the incidence of phlebitis in medical adult inpatients with peripheral venous catheter care bundle: a best practice implementation project
Authors: Gunasundram Sumathi , Tan Mary , Lim Koon Z.H. , Loh Veronica M.P.
Published: August 2020

Background:

One major complication of the insertion of a peripheral venous catheter (PVC) is phlebitis, often resulting in delay of treatment, increased healthcare costs and prolonged hospitalization.

Aims:

The current study sought to evaluate the effectiveness of a standardized PVC care bundle in increasing the compliance of PVC care and assessment and reduce the occurrences of phlebitis rates.

Methods:

A pre and postimplementation audit approach was used in this study and adopted the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice program. This study was carried out in three phases over a 10-month period, from March 2017 to December 2017 across three medical wards in a hospital in Singapore with a sample size of 90 patients. The study involved educating nurses on phlebitis assessment, implementing a PVC care bundle and monitoring compliance. An audit tool comprising four criteria from the Joanna Briggs Institute Practical Application of Clinical Evidence System was developed.

Results:

One-month and 3-month postimplementation findings revealed significant improvement in Criteria 1, 3 and 4 (P < 0.001) but no significant improvement in Criterion 2 (P > 0.05). Six-month postimplementation findings showed significant improvement in all four criteria (P < 0.05). An interesting finding was that the number of reported occurrences of phlebitis increased after implementing the PVC care bundle.

Discussion:

The increase in phlebitis rates could be attributed to the care bundle facilitating prompt and early identification of phlebitis. Despite the initial increase in occurrences 1 month post implementation, the general effectiveness of the care bundle in reducing occurrences of phlebitis was seen 6 months post implementation. The effectiveness of the care bundle to reduce phlebitis rates may be even more evident across a longer implementation period.

Conclusion:

The current study showed that the implementation of a standardized PVC care bundle can significantly enhance the assessment and identification process of phlebitis and can aid in reducing the incidence of phlebitis. The nurses’ compliance in practicing the PVC care bundle was determined by the post and preimplementation audits, thus, the audit approach was beneficial in translating evidence into practice.
Converting Microwave Ovens into Plasma-Generating Decontamination Units for N-95 Respirators
Authors: Ruzic David N. , Oh Chamteut , Puthussery Joseph V. , Verma Vishal , Nguyen Thanh H.
Published: August 2020

We show how a common microwave oven, a coat-hanger and a coffee cup can be used to decontaminate N-95 respirators in 30 seconds. Tulane virus in artificial saliva was reduced by >3 log and Geobacillus stearothermophilus spores were reduced by >6 log. Respirators maintained filtration and fitting after 10 cycles.
Throat wash as a source of SARS-CoV-2 RNA to monitor community spread of COVID-19
Authors: Lopez-Lopes Giselle Ibette , Ahagon Cintia , Benega Margarete Aparecida , Silva Daniela Bernardes Borges da , Silva Valéria Oliveira , Corrêa de Oliveira Santos Katia , Prado Lincoln Spinazola do , Santos Fabiana Pereira dos , Cilli Audrey , Saraceni Claudia , da Cruz Núria Borges , Afonso Ana Maria Sardinha , Timenetsky Maria do Carmo , de Macedo Brígido Luís Fernando ,   the IAL-COVID working group
Published: August 2020

Background

SARS-CoV-2 RNA detection with real time PCR is currently the central diagnostic tool to determine ongoing active infection. Nasopharyngeal and oral swabs are the main collection tool of biological material used as the source of viral RNA outside a hospital setting. However, limitation in swabs availability, trained health professional with proper PPE and potential risk of aerosols may hinder COVID diagnosis. Self-collection with swabs, saliva and throat wash to obtain oropharyngeal wash has been suggested as having comparable performance of regular swab. We performed throat wash (TW) based surveillance with laboratory heath workers and other employees (LHW) at a laboratory research institute.

Methods

Consecutive volunteer testing of LWH and external household and close contacts were included. TW self-collection was performed in 5 mL of sterile saline that was returned to original vial after approximate 5 secs of gargle. RNA extraction and rtPCR were performed as part of routine COVID protocols using Allplex (Seegene, Korea).

Results

Four hundred and twenty two volunteers, 387 (93%) LHW and 43 (7%) contacts participated in the survey. One or more positive COVID rtPCR was documented in 63 (14.9% CI95 12%-19%) individuals. No correlation was observed between with direct activities with COVID samples to positivity, with infection observed in comparable rates among different laboratory areas, administrative or supportive activities. Among 63 with detected SARS-CoV-2 RNA, 59 with clinical information, 58% reported symptoms at a median of 4 days prior to collection, most with mild disease. Over a third (38%) of asymptomatic cases developed symptoms 1-3 days after collection. Although overall CT values of TW were higher than that of contemporary swab tests from hospitalized cases, TW from symptomatic cases had comparable CTs.

Conclusions

The study suggests that TW may be a valid alternative to the detection of SARS-CoV-2 RNA. The proportion of asymptomatic and pre-symptomatic cases is elevated and reinforces the need of universal precautions and frequent surveys to limit the spread of the disease.
Long-term patient-reported symptoms of COVID-19: an analysis of social media data
Authors: Banda Juan M. , Singh Gurdas Viguruji , Alser Osaid H. , Prieto-Alhambra Daniel
Published: August 2020

As the COVID-19 virus continues to infect people across the globe, there is little understanding of the long term implications for recovered patients. There have been reports of persistent symptoms after confirmed infections on patients even after three months of initial recovery. While some of these patients have documented follow-ups on clinical records, or participate in longitudinal surveys, these datasets are usually not publicly available or standardized to perform longitudinal analyses on them. Therefore, there is a need to use additional data sources for continued follow-up and identification of latent symptoms that might be underreported in other places. In this work we present a preliminary characterization of post-COVID-19 symptoms using social media data from Twitter. We use a combination of natural language processing and clinician reviews to identify long term self-reported symptoms on a set of Twitter users.
Prevalence of Iron, Vitamin B12 deficiency and inflammatory anaemia in treatment naive individual consecutive cancer patients: A cross sectional study
Authors: Pandey A , Singh S , Aryan R , Murari K
Published: August 2020

Background

In treatment naive Indian cancer patients, prevalence of iron, B12 deficiency and inflammatory anaemia in poorly known.

Aims and Objectives

To evaluate prevalence of anaemia and iron, B12 deficiency along with inflammation in treatment naive individual consecutive cancer patients.

Material and Methods

All patients registered from 1st July 2019 till 31st December 2019 in Medical Oncology Outpatient Department were offered to undergo Iron profile, Serum B12 levels and Serum ferritin along with routine haematological investigations. Anaemia was defined as Haemoglobin < 11gm/dL. Transferrin saturation <20%, Serum Ferritin >300 microgram/litre and Vitamin B12 level <200 picogram/millilitre were ‘cut-offs’ used to define iron deficiency, inflammation and Vitamin B12 deficiency respectively. Data was analysed using descriptive statistics, frequency distribution, crosstabs and Bar Diagram in SPSS version 17.0. Pearsons Chi square test and Odds ratio was used to measure the strength of association with variables.

Results

311/441 (70.5%) were found eligible. Median age was 52 ± 15.9 (Range 18-84) years with 144/331(46%) females. The prevalence of anaemia was 61% ± 2.7 (95% CI 55-66%). Mean Haemoglobin was 9.86 ± 2.08 (range 3-16) gram/decilitre. 21/311(7%) had severe anaemia (Haemoglobin < 6.9 gm/dl). 135/311 (71%), 61/189 (32%) and 89/189 (47%) anaemic patients had iron deficiency, inflammation and B12 deficiency respectively. More than 70% of Gastrointestinal (50/69), Gynaecological(17/24) and Lung Cancer(18/22) patients had underling Iron deficiency.

Conclusion

Two-third of cancer patients are iron deficient. B12 deficiency and inflammation are present in half and one-third patients respectively.
KL-VS heterozygosity is associated with reduced tau accumulation and lower memory impairment in Alzheimer’s disease
Authors: Neitzel Julia , Franzmeier Nicolai , Rubinski Anna , Dichgans Martin , Brendel Matthias , Malik Rainer , Ewers Michael ,   for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: August 2020

Klotho-VS heterozygosity (KL-VShet) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VShet is associated with lower levels of pathologic tau, i.e. the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VShet and levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 354 controls and patients within the AD continuum. KL-VShet showed lower cross-sectional increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This effect of KL-VShet on tau-PET showed a tendency to be stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VShet was related to better memory functions and this association was mediated by lower tau-PET. Amyloid-PET levels did not differ between KL-VShet carriers versus non-carriers. Together, our findings provide evidence for a protective role of KL-VShet against tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.
Household transmission of SARS-CoV-2: a systematic review and meta-analysis of secondary attack rate
Authors: Madewell Zachary J. , Yang Yang , Longini Ira M. , Halloran M. Elizabeth , Dean Natalie E.
Published: August 2020

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spread by direct, indirect, or close contact with infected people via infected respiratory droplets or saliva. Crowded indoor environments with sustained close contact and conversations are a particularly high-risk setting.

Methods

We performed a meta-analysis through July 29, 2020 of SARS-CoV-2 household secondary attack rate (SAR), disaggregating by several covariates (contact type, symptom status, adult/child contacts, contact sex, relationship to index case, index case sex, number of contacts in household, coronavirus).

Findings

We identified 40 relevant published studies that report household secondary transmission. The estimated overall household SAR was 18·8% (95% confidence interval [CI]: 15·4%–22·2%), which is higher than previously observed SARs for SARS-CoV and MERS-CoV. We observed that household SARs were significantly higher from symptomatic index cases than asymptomatic index cases, to adult contacts than children contacts, to spouses than other family contacts, and in households with one contact than households with three or more contacts.

Interpretation

To prevent the spread of SARS-CoV-2, people are being asked to stay at home worldwide. With suspected or confirmed infections referred to isolate at home, household transmission will continue to be a significant source of transmission.
Manuscript title: Loss in the expansion of SARS-CoV-2 specific immunity is a key risk factor in fatal patients with COVID-19
Authors: Zeng Qiang , Huang Gang , Li Yong-zhe , Xu Guoqiang , Dong Sheng-yong , Zhong Tian-yu , Chen Zong-tao , Xu Yang
Published: August 2020

Knowledge of the dynamic immunological characteristics of patients with coronavirus disease 2019 (COVID-19) is essential for clinicians to understand the progression of the disease. Our data showed that the immune system and function gradually remodeled and declined with age, starting from age 16 until age 91 in 25,239 healthy controls. An analysis of the relationship between the number of lymphocytes and age revealed that the lymphocyte and subset counts tended to decline with age significantly. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity declined with age and was associated with survival time in fatal cases. Loss in the expansion of SARS-CoV-2-specific immunity could be expanded in vitro. The concurrent decline in SARS-CoV-2-specific cellular and humoral immunities and prolonged SARS-CoV-2 exposure predicted fatal outcomes. Our findings provide a basis for further analysis of SARS-CoV-2-specific immunity and understanding of the pathogenesis of fatal COVID-19 cases.

Highlights

The immune system and function gradually remodeled and declined with age.

SARS-CoV-2-specific immunity declined with age in fatal cases.

SARS-CoV-2-specific immunity was associated with survival time in fatal cases.

Loss in the expansion of SARS-CoV-2-specific immunity could be expanded in vitro.

A concurrent decline in SARS-CoV-2-specific cellular and humoral immunities and prolonged SARS-CoV-2 exposure predicted fatal outcomes.
COVID-19 Recurrent Varies with Different Combinatorial Medical Treatments Determined by Machine Learning Approaches
Authors: Huang Jia , Zhai Song , Ye Fangfan , Wang Song , Zeng Manfei , Way George , Madahar Vipul , Zhu Tengfei , Qiu Liping , Xu Zehui , Ye Manhua , Liu Lei , Cui Xinping , Liao Jiayu
Published: August 2020

Various medical treatments for COVID-19 are attempted. After patients are discharged, SARS-CoV-2 recurring cases are reported and the recurrence could profoundly impact patient healthcare and social economics. To date, no data on the effects of medical treatments on recurrence has been published. We analyzed the treatment data of combinations of ten different drugs for the recurring cases in a single medical center, Shenzhen, China. A total of 417 patients were considered and 414 of them were included in this study (3 deaths) with mild-to-critical COVID-19. Patients were treated by 10 different drug combinations and followed up for recurrence for 28 days quarantine after being discharged from the medical center between February and May, 2020. We applied the Synthetic Minority Oversampling Technique (SMOTE) to overcome the rare recurring events in certain age groups and performed Virtual Twins (VT) analysis facilitated by random forest regression for medical treatment-recurrence classification. Among those drug combinations, Methylprednisolone/Interferon/Lopinavir/Ritonavir/Arbidol led to the lowest recurring rate (0.133) as compared to the average recurring rate (0.203). For the younger group (age 20-27) or the older group (age 60-70), the optimal drug combinations are different, but the above combination is still the second best. For obese patients, the combination of Ribavirin/Interferon/Lopinavir/Ritonavir/Arbidol led to the lowest recurring rate for age group of 20-50, whereas the combination of Interferon/Lopinavir/Ritonavir/Arbidol led to lowest recurring rate for age group of 50-70. The insights into combinatorial therapy we provided here shed lights on the use of a combination of (biological and chemical) anti-virus therapy and/or anti-cytokine storm as a potentially effective therapeutic treatment for COVID-19.
Analysis of the correlation between anti-MDA5 antibody and the severity of COVID-19: a retrospective study
Authors: Liu Changzheng , Wang Qian , Wang Yeming , Wang Geng , Wang Linghang , Chen Hong , Jiao Tao , Hu Chaojun , Lei Xiaobo , Guo Li , Ren Lili , Li Mengtao , Zeng Xiaofeng , Zhang Dingyu , Cao Bin , Wang Jianwei
Published: August 2020

OBJECTIVE

To identify the anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) in coronavirus disease 2019 (COVID-19) and its relationship with the severity and clinical outcomes of COVID-19.

DESIGN

Retrospective cohort study.

SETTING

Three hospitals in China.

PARTICIPANTS

274 adult inpatients diagnosed with COVID-19 according to the Protocol for Prevention and Control of COVID-19 (Edition 7) of China and confirmed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) RNA testing, were included from three hospitals from Wuhan, Harbin and Beijing, China from 1 December 2019 to 19 April 2020. The Biobank of Myositis Registry Department of Rheumatology, Peking Union Medical College Hospital, provided the plasma of five patients with anti-MDA5 Ab-related dermatomyositis as positive control group. Demographic, clinical and laboratory data were collected from medical records. The anti-MDA5 Ab was determined by an ELISA assay and was verified by immunoblotting analysis.

MAIN OUTCOME MEASURES

In hospital death of all cause.

RESULTS

The positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% (132/274) and the anti-MDA5 Ab positive patients tended to represent with severe disease (88.6% vs 66.9%, P<0.0001). The titer of anti-MDA5 Ab was significantly elevated in the non-survivals (5.95±5.16 vs 8.22±6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding to severe COVID-19 patients, we found that high titer of anti-MDA5 Ab (≥10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones.

CONCLUSION

Anti-MDA5 Ab was prevalent in the COVID-19 patients and high titer of this antibody is correlated with severe disease and unfavorable outcomes. Early screening and serially monitoring of anti-MDA5 Ab titer have the potential to predict the disease progression of COVID-19.
Comparative experimental evidence on compliance with social distancing during the COVID-19 pandemic
Authors: Becher Michael , Stegmueller Daniel , Brouard Sylvain , Kerrouche Eric
Published: August 2020

Social distancing is a central public health measure in the fight against the COVID-19 pandemic, but individuals’ compliance cannot be taken for granted. We use a survey experiment to examine the prevalence of non-compliance with social distancing in nine countries and test pre-registered hypotheses about individual-level characteristics associated with less social distancing. Leveraging a list experiment to control for social desirability bias, we find large cross-national variation in adherence to social distancing guidelines. Compliance varies systematically with COVID-19 fatalities and the strictness of lockdown measures. We also find substantial heterogeneity in the role of individual-level predictors. While there is an ideological gap in social distancing in the US and New Zealand, this is not the case in European countries. Taken together, our results suggest caution when trying to model pandemic health policies on other countries’ experiences. Behavioral interventions targeted towards specific demographics that work in one context might fail in another.
Whether the Weather Will Help Us Weather the COVID-19 Pandemic: Using Machine Learning to Measure Twitter Users’ Perceptions
Authors: Gupta Marichi , Bansal Aditya , Jain Bhav , Rochelle Jillian , Oak Atharv , Jalali Mohammad S.
Published: August 2020

Objective

The potential ability for weather to affect SARS-CoV-2 transmission has been an area of controversial discussion during the COVID-19 pandemic. Individuals’ perceptions of the impact of weather can inform their adherence to public health guidelines; however, there is no measure of their perceptions. We quantified Twitter users’ perceptions of the effect of weather and analyzed how they evolved with respect to real-world events and time.

Materials and Methods

We collected 166,005 tweets posted between January 23 and June 22, 2020 and employed machine learning/natural language processing techniques to filter for relevant tweets, classify them by the type of effect they claimed, and identify topics of discussion.

Results

We identified 28,555 relevant tweets and estimate that 40.4% indicate uncertainty about weather’s impact, 33.5% indicate no effect, and 26.1% indicate some effect. We tracked changes in these proportions over time. Topic modeling revealed major latent areas of discussion.

Discussion

There is no consensus among the public for weather’s potential impact. Earlier months were characterized by tweets that were uncertain of weather’s effect or claimed no effect; later, the portion of tweets claiming some effect of weather increased. Tweets claiming no effect of weather comprised the largest class by June. Major topics of discussion included comparisons to influenza’s seasonality, President Trump’s comments on weather’s effect, and social distancing.

Conclusion

There is a major gap between scientific evidence and public opinion of weather’s impacts on COVID-19. We provide evidence of public’s misconceptions and topics of discussion, which can inform public health communications.
Developing methods for measuring national distributions and densities of wild mammals using camera traps: A Kosovo study
Authors: Beatham Sarah E. , Ward Alastair I. , Fouracre David , Muhaxhiri Jeton , Sallmann Michael , Zogu Besim , Gjinovci Valdet , Wilsmore Anthony J. , Smith Graham C.
Published: August 2020

Understanding the distributions and density of wild mammals is integral to the implementation of wildlife management strategies, particularly for controlling diseases and conservation management. Recent advances in camera trap technology together with the development of the Random Encounter Model have provided a non-invasive method for estimating mammal densities. In addition, the development of citizen science initiatives have advanced ecological data collection. This study describes a national camera trap survey delivered by local stakeholders in eleven forest sites in Kosovo from 2014 to 2015 to measure the distributions and abundance of medium to large wild mammals as part of the Control and/or eradication of animal diseases project. The Random Encounter Model was used to calculate density data for each species, which appear realistic when compared to densities found in other European countries. The study particularly focussed on the red fox (Vulpes vulpes) and the grey wolf (Canis lupus) as potential vectors of rabies and wild boar (Sus scrofa) as a vector of classical swine fever. These species were found to be three of the most widely distributed species in Kosovo and were present at the majority of sites at high densities. The camera survey also provided information on species of conservation concern such as the Eurasian brown bear (Ursus arctos) and provided the first physical evidence of a live Eurasian golden jackal (Canis aureus) in Kosovo. Although sources of bias were identified, these estimates are likely to be more accurate than those devised from methods such as hunting bags and the findings of this study suggest that, with a moderate amount of development, camera trapping implemented by local stakeholders can be used as an effective and practicable method to estimate national distributions and population sizes of medium to large sized wild mammals.
A composite method to infer drug resistance with mixed genomic data
Authors: Datta Gargi , Hasan Nabeeh A , Strong Michael , Leach Sonia M
Published: August 2020

Background

The increasing incidence of drug resistance in tuberculosis and other infectious diseases poses an escalating cause for concern, emphasizing the urgent need to devise robust computational and molecular methods identify drug resistant strains. Although machine learning-based approaches using whole-genome sequence data can facilitate the inference of drug resistance, current implementations do not optimally take advantage of information in public databases and are not robust for small sample sizes and mixed attribute types.

Results

In this paper we introduce the Composite MetaDistance method, an approach for feature selection and classification of high-dimensional, unbalanced datasets with mixed attribute features from various data sources. We introduce a mixed-attribute, multi-view distance function to calculate distances between samples, with optimal handling of nominal features and different feature views. We also introduce a novel feature set for drug resistance prediction inMycobacterium tuberculosis, using data from diverse sources. We compare the performance of Composite MetaDistance to multiple machine learning algorithms forMycobacterium tuberculosisdrug resistance prediction for three drugs. Composite MetaDistance consistently outperforms existing algorithms for small sample training sets, and performs as well as other algorithms for training sets with larger sample sizes.

Conclusion

The feature set formulation introduced in this paper is utilizes mutational and publicly available information for each gene, and is much richer than ever devised previously. The prediction algorithm, Composite MetaDistance, is sample size agnostic and robust especially given small sample sizes. Proper handling of nominal features improves performance even with a very small number of nominal features. We expect Composite MetaDistance to be even more robust for datasets with a higher percentage of nominal features. The algorithm is application independent and can be used for any mixed attribute dataset.
Modeling latent infection transmissions through biosocial stochastic dynamics
Authors: Tadić Bosiljka , Melnik Roderick
Published: August 2020

The events of the recent SARS-CoV-02 epidemics have shown the importance of social factors, especially given the large number of asymptomatic cases that effectively spread the virus, which can cause a medical emergency to very susceptible individuals. Besides, the SARS-CoV-02 virus survives for several hours on different surfaces, where a new host can contract it with a delay. These passive modes of infection transmission remain an unexplored area for traditional mean-field epidemic models. Here, we design an agent-based model for simulations of infection transmission in an open system driven by the dynamics of social activity; the model takes into account the personal characteristics of individuals, as well as the survival time of the virus and its potential mutations. A growing bipartite graph embodies this biosocial process, consisting of active carriers (host) nodes that produce viral nodes during their infectious period. With its directed edges passing through viral nodes between two successive hosts, this graph contains complete information about the routes leading to each infected individual. We determine temporal fluctuations of the number of exposed and the number of infected individuals, the number of active carriers and active viruses at hourly resolution. The simulated processes underpin the latent infection transmissions, contributing significantly to the spread of the virus within a large time window. More precisely, being brought by social dynamics and exposed to the currently existing infection, an individual passes through the infectious state until eventually spontaneously recovers or otherwise is moves to a controlled hospital environment. Our results reveal complex feedback mechanisms that shape the dependence of the infection curve on the intensity of social dynamics and other sociobiological factors. In particular, the results show how the lockdown effectively reduces the spread of infection and how it increases again after the lockdown is removed. Furthermore, a reduced level of social activity but prolonged exposure of susceptible individuals have adverse effects. On the other hand, virus mutations that can gradually reduce the transmission rate by hopping to each new host along the infection path can significantly reduce the extent of the infection, but can not stop the spreading without additional social strategies. Our stochastic processes, based on graphs at the interface of biology and social dynamics, provide a new mathematical framework for simulations of various epidemic control strategies with high temporal resolution and virus traceability.
Social Learning in a Network Model of Covid-19
Authors: Davids Allan , Rand Gideon Du , Georg Co-Pierre , Koziol Tina , Schasfoort Joeri Anton
Published: August 2020

This paper studies the effects of social learning on the transmission of Covid-19 in a network model. We calibrate our model to detailed data for Cape Town, South Africa and show that the inclusion of social learning improves the prediction of excess fatalities, reducing the best-fit squared difference from 19.34 to 11.40. The inclusion of social learning both flattens and shortens the curves for infections, hospitalizations, and excess fatalities, which is qualitatively different from flattening the curve by reducing the contact rate or transmission probability through non-pharmaceutical interventions. While social learning reduces infections, this alone is not sufficient to curb the spread of the virus because learning is slower than the disease spreads. We use our model to study the efficacy of different vaccination strategies and find that vaccinating vulnerable groups first leads to a 72% reduction in fatalities and 5% increase in total infections compared to a random-order benchmark. By contrast, using a contact-based vaccination strategy reduces infections by only 0.9% but results in 42% more fatalities relative to the benchmark.
High speed, three-dimensional imaging reveals chemotactic behavior specific to human-infectiveLeishmaniaparasites
Authors: Findlay Rachel C. , Osman Mohamed , Spence Kirsten A. , Kaye Paul M. , Walrad Pegine B. , Wilson Laurence G.
Published: August 2020

Cellular motility is an ancient eukaryotic trait, ubiquitous across phyla with roles in predator avoidance, resource access and competition. Flagellar-dependent motility is seen in a variety of parasitic protozoans and morphological changes in flagellar structure and function have been qualitatively described during differentiation. However, whether the dynamics of flagellar motion vary across lifecycle stages and whether such changes serve to facilitate human infection is not known. Here we used holographic video microscopy to study the pattern of motility in insect midgut forms ofLeishmania(procyclic promastigotes; PCF) and differentiated human infective metacyclic promastigotes (META). We discovered that PCF swim in a slow, corkscrew motion around a gently curving axis while META display ‘run and tumble’ behaviour in the absence of stimulus, reminiscent of bacterial behaviour. In addition, we demonstrate that META specifically respond to a macrophage-derived stimulus, modifying swimming direction and speed to target host immune cells. Thus, the motility strategy employed byLeishmaniaappears as a random search that is replaced with a ballistic swimming motion in the presence of an immunological stimulus. These findings shed unique insights into how flagellar motion adapts to the particular needs of the parasite at different times in its lifecycle and define a new pre-adaptation for infection of the human host.
DPCfam: a new method for unsupervised protein family classification
Authors: Russo Elena Tea , Laio Alessandro , Punta Marco
Published: August 2020

Motivation

As the UniProt database approaches the 200 million entries’ mark, the vast majority of proteins it contains lack any experimental validation of their functions. In this context, the identification of homologous relationships between proteins remains the single most widely applicable tool for generating functional and structural hypotheses in silico. Although many databases exist that classify proteins and protein domains into homologous families, large sections of the sequence space remain unassigned.

Results

We introduce DPCfam, a new unsupervised procedure that uses sequence alignments and Density Peak Clustering to automatically classify homologous protein regions. Here, we present a proof-of-principle experiment based on the analysis of two clans from the Pfam protein family database. Our tests indicate that DPCfam automatically-generated clusters are generally evolutionary accurate corresponding to one or more Pfam families and that they cover a significant fraction of known homologs. Overall, DPCfam shows potential both for assisting manual annotation efforts (domain discovery, detection of classification inconsistencies, improvement of family coverage and boosting of clan membership) and as a stand-alone tool for unsupervised classification of sparsely annotated protein datasets such as those from environmental metagenomics studies (domain discovery, analysis of domain diversity).

Availability

Algorithm implementation used in this paper is available athttps://gitlab.com/ETRu/dpcfam(Requires Python 3, C++ compiler and runs on Linux systems.); data are available athttps://zenodo.org/record/3934399
The deep and slow breathing characterizing rest favors brain respiratory-drive
Authors: Girin Baptiste , Juventin Maxime , Garcia Samuel , Lefèvre Laura , Amat Corine , Fourcaud-Trocmé Nicolas , Buonviso Nathalie
Published: August 2020

A respiration-locked activity in the olfactory brain, mainly originating in the mechano-sensitivity of olfactory sensory neurons to air pressure, propagates from the olfactory bulb to the rest of the brain. Interestingly, changes in nasal airflow rate result in reorganization of olfactory bulb response. Therefore, if the respiratory drive of the brain originates in nasal airflow movements, then it should vary with respiration dynamics that occur spontaneously during natural conditions. We took advantage of the spontaneous variations of respiration dynamics during the different waking and sleep states to explore respiratory drive in various brain regions. We analyzed their local field potential activity relative to respiratory signal. We showed that respiration regime was state-specific, and that quiet waking was the only vigilance state during which all the recorded structures can be respiration-driven whatever the respiration frequency. We used a CO2-enriched air to change the respiratory regime associated to each state and, using a respiratory cycle-by-cycle analysis, we evidenced that the large and strong brain entrainment during quiet waking was the consequence of its associated respiration regime consisting in an optimal trade-off between deepness and duration of inspiration. These results show for the first time that changes in respiration regime alter the cortical dynamics and that the respiratory regime associated with rest is optimal for respiration to drive the brain.
The morphology and evolution of chondrichthyan cranial muscles: a digital dissection of the elephantfishCallorhinchus miliiand the catsharkScyliorhinus canicula
Authors: Dearden Richard P. , Mansuit Rohan , Cuckovic Antoine , Herrel Anthony , Didier Dominique , Tafforeau Paul , Pradel Alan
Published: August 2020

The anatomy of sharks, rays, and chimaeras (chondrichthyans) is crucial to understanding the evolution of the cranial system in vertebrates, due to their position as the sister group to bony fishes (osteichthyans). Strikingly different arrangements of the head in the two constituent chondrichthyan groups – holocephalans and elasmobranchs – have played a pivotal role in the formation of evolutionary hypotheses targeting major cranial structures such as the jaws and pharynx. However, despite the advent of digital dissections as a means of easily visualizing and sharing the results of anatomical studies in three dimensions, information on the musculoskeletal systems of the chondrichthyan head remains largely limited to traditional accounts, many of which are at least a century old. Here we use synchrotron tomography acquire 3D data which we used to carry out a digital dissection of a holocephalan and an elasmobranch widely used as model species: the elephantfish,Callorhinchus milii, and the small-spotted catshark, Scyliorhinus canicula. We describe and figure the skeletal anatomy of the head, labial, mandibular, hyoid, and branchial cartilages in both taxa as well as the muscles of the head and pharynx. We make new observations, particularly regarding the branchial musculature ofCallorhinchus, revealing several previously unreported or previously ambiguous structures. Finally, we review what is known about the evolution of chondrichthyan cranial muscles from their fossil record and discuss the implications for muscle homology and evolution, broadly concluding that the holocephalan pharynx is likely derived from a more elasmobranch-like form. This dataset has great potential as a resource, particularly for researchers using these model species for zoological research, functional morphologists requiring models of musculature and skeletons, as well as for palaeontologists seeking comparative models for extinct taxa.
THE REGULATORY EFFECT OF LIGHT OVER FRUIT DEVELOPMENT AND RIPENING IS MEDIATED BY EPIGENETIC MECHANISMS
Authors: Bianchetti Ricardo , Bellora Nicolas , de Haro Luis A , Zuccarelli Rafael , Rosado Daniele , Freschi Luciano , Rossi Magdalena , Bermudez Luisa
Published: August 2020

Phytochrome-mediated light and temperature perception has been shown to be a major regulator of fruit development. Furthermore, chromatin remodelling via DNA demethylation has been described as a crucial mechanism behind the fruit ripening process; however, the molecular basis underlying the triggering of this epigenetic modification remains largely unknown. Here, through integrative analyses of the methylome, siRNAome and transcriptome of tomato fruits fromphyAandphyB1B2null mutants, we report that PHYB1 and PHYB2 control genome-wide DNA methylation during fruit development from green towards ripe stages. The experimental evidence indicates that PHYB1B2 signal transduction is mediated by a gene expression network involving chromatin organization factors (DNA methylases/demethylases, histone-modifying enzymes and remodelling factors) and transcriptional regulators leading in the altered mRNA profile of photosynthetic and ripening-associated genes. This new level of understanding provides insights into the orchestration of epigenetic mechanisms in response to environmental cues affecting agronomical traits.
Predicting the future development of mild cognitive impairment in the cognitively healthy elderly
Authors: Strange Bryan A. , Zhang Linda , Sierra-Marcos Alba , Alfayate Eva , Tohka Jussi , Medina Miguel
Published: August 2020

Identifying measures that predict future cognitive impairment in healthy individuals is necessary to inform treatment strategies for candidate dementia-preventative and modifying interventions. Here, we derive such measures by studying “converters” who transitioned from cognitively normal at baseline to mild-cognitive impairment (MCI) in a longitudinal study of 1213 elderly participants. We first establish reduced grey matter density (GMD) in left entorhinal cortex (EC) as a biomarker for impending cognitive decline in healthy individuals, employing a matched sampling control for several dementia risk-factors, thereby mitigating the potential effects of bias on our statistical tests. Next, we determine the predictive performance of baseline demographic, genetic, neuropsychological and MRI measures by entering these variables into an elastic net-regularized classifier. Our trained statistical model classified converters and controls with validation Area-Under-the-Curve>0.9, identifying only delayed verbal memory and left EC GMD as relevant predictors for classification. This performance was maintained on test classification of out-of-sample converters and controls. Our results suggest a parsimonious but powerful predictive model for MCI development in the cognitively healthy elderly.
The SARS-CoV-2 Nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein
Authors: Lu Shan , Ye Qiaozhen , Singh Digvijay , Villa Elizabeth , Cleveland Don W. , Corbett Kevin D.
Published: August 2020

The multifunctional nucleocapsid (N) protein in SARS-CoV-2 binds the ~30 kb viral RNA genome to aid its packaging into the 80-90 nm membrane-enveloped virion. The N protein is composed of N-terminal RNA-binding and C-terminal dimerization domains that are flanked by three intrinsically disordered regions. Here we demonstrate that a centrally located 40 amino acid intrinsically disordered domain drives phase separation of N protein when bound to RNA, with the morphology of the resulting condensates affected by inclusion in the RNA of the putative SARS-CoV-2 packaging signal. The SARS-CoV-2 M protein, normally embedded in the virion membrane with its C-terminus extending into the virion core, independently induces N protein phase separation that is dependent on the N protein’s C-terminal dimerization domain and disordered region. Three-component mixtures of N+M+RNA form condensates with mutually exclusive compartments containing N+M or N+RNA, including spherical annular structures in which the M protein coats the outside of an N+RNA condensate. These findings support a model in which phase separation of the N protein with both the viral genomic RNA and the SARS-CoV-2 M protein facilitates RNA packaging and virion assembly.
The first steps toward a global pandemic: Reconstructing the demographic history of parasite host switches in its native range
Authors: Techer Maeva A. , Roberts John M. K. , Cartwright Reed A , Mikheyev Alexander S.
Published: August 2020

Background

Host switching allows parasites to expand their niches. However, successful switching may require suites of adaptations and also may decrease performance on the old host. As a result, reductions in gene flow accompany many host switches, driving speciation. Because host switches tend to be rapid, it is difficult to study them in real-time and their demographic parameters remain poorly understood. As a result, fundamental factors that control subsequent parasite evolution, such as the size of the switching population or the extent of immigration from the original host, remain largely unknown. To shed light on the host switching process, we explored how host switches occur in independent host shifts by two ectoparasitic honey bee mites (Varroa destructor and V. jacobsoni).

Results

Both switched to the western honey bee (Apis mellifera) after it was brought into contact with their ancestral host (Apis cerana), ∼70 and ∼12 years ago, respectively. Varroa destructor subsequently caused worldwide collapses of honey bee populations. Using whole-genome sequencing on 63 mites collected in their native ranges from both the ancestral and novel hosts, we were able to reconstruct the known temporal dynamics of the switch. We further found multiple previously undiscovered mitochondrial lineages on the novel host, along with the genetic equivalent of tens of individuals that were involved in the initial host switch. Despite being greatly reduced, some gene flow remains between mites adapted to different hosts.

Conclusion

Our findings suggest that while reproductive isolation may facilitate the fixation of traits beneficial for exploitation of the new host, ongoing genetic exchange may allow genetic amelioration of inbreeding effects.
Root electrotropism in Arabidopsis does not depend on auxin distribution but requires cytokinin biosynthesis
Authors: Salvalaio Maddalena , Oliver Nicholas , Tiknaz Deniz , Schwarze Maximillian , Kral Nicolas , Kim Soo-Jeong , Sena Giovanni
Published: August 2020

An efficient foraging strategy for plant roots relies on the ability to sense multiple physical and chemical cues in soil and to reorient growth accordingly (tropism). Root tropisms range from sensing gravity (gravitropism), light (phototropism), water (hydrotropism), touch (thigmotropism) and more. Electrotropism, also known as galvanotropism, is the phenomenon of aligning growth with external electric fields and currents. Although observed in a few species since the end of the 19thcentury, the molecular and physical mechanism of root electrotropism remains elusive, limiting the comparison to more defined sensing pathways in plants.

Here we provide a first quantitative and molecular characterisation of root electrotropism in the model systemArabidopsis thaliana, showing that it does not depend on an asymmetric distribution of the plant hormone auxin, but that instead it requires the biosynthesis of a second hormone, cytokinin. We also show that the dose-response kinetics of the early steps of root electrotropism follows a power law analogous to the one observed in some physiological reactions in animals.

A future full molecular and quantitative characterisation of root electrotropism would represent a step forward towards a better understanding of signal integration in plants, and an independent outgroup for comparative analysis of electroreception in animals and fungi.