bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating epidemic coupling between populations from the time to invasion
Authors: Hempel Karsten , Earn David J. D.
Published: November 2020

Identifying the mechanisms by which diseases spread among populations is important for understanding and forecasting patterns of epidemics and pandemics. Estimating transmission coupling among populations is challenging because transmission events are difficult to observe in practice, and connectivity among populations is often obscured by local disease dynamics. We consider the common situation in which an epidemic is seeded in one population and later spreads to a second population. We present a method for estimating transmission coupling between the two populations, assuming they can be modelled assusceptible–infected–removed(SIR) systems. We show that the strength of coupling between the two populations can be estimated from the time taken for the disease to invade the second population. Confidence in the estimate is low if only a single invasion event has been observed, but is substantially improved if numerous independent invasion events are observed. Our analysis of this simplest, idealized scenario represents a first step toward developing and verifying methods for estimating epidemic coupling among populations in an ever-more-connected global human population.
Signalling through cerebral cavernous malformation protein networks
Authors: Su Valerie L. , Calderwood David A.
Published: November 2020

Cerebral cavernous malformations (CCMs) are neurovascular abnormalities characterized by thin, leaky blood vessels resulting in lesions that predispose to haemorrhages, stroke, epilepsy and focal neurological deficits. CCMs arise due to loss-of-function mutations in genes encoding one of three CCM complex proteins, KRIT1, CCM2 or CCM3. These widely expressed, multi-functional adaptor proteins can assemble into a CCM protein complex and (either alone or in complex) modulate signalling pathways that influence cell adhesion, cell contractility, cytoskeletal reorganization and gene expression. Recent advances, including analysis of the structures and interactions of CCM proteins, have allowed substantial progress towards understanding the molecular bases for CCM protein function and how their disruption leads to disease. Here, we review current knowledge of CCM protein signalling with a focus on three pathways which have generated the most interest—the RhoA–ROCK, MEKK3–MEK5–ERK5–KLF2/4 and cell junctional signalling pathways—but also consider ICAP1-β1 integrin and cdc42 signalling. We discuss emerging links between these pathways and the processes that drive disease pathology and highlight important open questions—key among them is the role of subcellular localization in the control of CCM protein activity.
Cytoplasmic mRNA recapping has limited impact on proteome complexity
Authors: Agana Bernice A. , Wysocki Vicki H. , Schoenberg Daniel R.
Published: November 2020

The m7G cap marks the 5′ end of all eukaryotic mRNAs, but there are also capped ends that map downstream within spliced exons. A portion of the mRNA transcriptome undergoes a cyclical process of decapping and recapping, termed cap homeostasis, which impacts the translation and stability of these mRNAs. Blocking cytoplasmic capping results in the appearance of uncapped 5′ ends at native cap sites but also near downstream cap sites. If translation initiates at these sites the products would lack the expected N-terminal sequences, raising the possibility of a link between mRNA recapping and proteome complexity. We performed a shotgun proteomics analysis on cells carrying an inducible inhibitor of cytoplasmic capping. A total of 21 875 tryptic peptides corresponding to 3565 proteins were identified in induced and uninduced cells. Of these, only 29 proteins significantly increased, and 28 proteins significantly decreased, when cytoplasmic capping was inhibited, indicating mRNA recapping has little overall impact on protein expression. In addition, overall peptide coverage per protein did not change significantly when cytoplasmic capping was inhibited. Together with previous work, our findings indicate cap homeostasis functions primarily in gating mRNAs between translating and non-translating states, and not as a source of proteome complexity.
Foraging niche overlap during chick-rearing in the sexually dimorphic Westland petrel
Authors: Poupart Timothée A. , Waugh Susan M. , Kato Akiko , Arnould John P. Y.
Published: November 2020

Most Procellariform seabirds are pelagic, breed in summer when prey availability peaks, and migrate for winter. They also display a dual foraging strategy (short and long trips) and sex-specific foraging. The Westland petrelProcellaria westlandica, a New Zealand endemic, is one of the rare seabirds breeding in winter. Preliminary findings on this large and sexually dimorphic petrel suggest a foraging behaviour with no evidence of a dual strategy, within a narrow range and with shared areas between sexes. To investigate further this unusual strategy, the present study determined the fine-scale at-sea behaviours (global positioning system and accelerometer data loggers) and trophic niches (stable isotopes in whole blood) of chick-rearing individuals (16 males and 13 females). All individuals foraged on the shelf-slope of the west coast of New Zealand's South Island with short, unimodal trips. Both sexes foraged at similar intensity without temporal, spatial or isotopic niche segregation. These findings suggest the presence of a winter prey resource close to the colony, sufficient to satisfy the nutritional needs of breeding without increasing the foraging effort or intra-specific competition avoidance during winter. Additional data are needed to assess the consistency of foraging niche between the sexes and its reproductive outcomes in view of anticipated environmental changes.
Terpyridine-metal complexes: effects of different substituents on their physico-chemical properties and density functional theory studies
Authors: Mughal Ehsan Ullah , Mirzaei Masoud , Sadiq Amina , Fatima Sana , Naseem Ayesha , Naeem Nafeesa , Fatima Nighat , Kausar Samia , Altaf Ataf Ali , Zafar Muhammad Naveed , Khan Bilal Ahmad
Published: November 2020

A series of different substituted terpyridine (tpy)-based ligands have been synthesized by Kröhnke method. Their binding behaviour was evaluated by complexing them with Co(II), Fe(II) and Zn(II) ions, which resulted in interesting coordination compounds with formulae, [Zn(tpy)
2
]PF
6
, [Co(tpy)
2
](PF
6
)
2
, [Fe(tpy)
2
](PF
6
)
2
and interesting spectroscopic properties. Their absorption and emission behaviours in dilute solutions were investigated in order to explain structure–property associations and demonstrate the impact of different aryl substituents on the terpyridine scaffold as well as the role of the metal on the complexes. Photo-luminescence analysis of the complexes in acetonitrile solution revealed a transition from hypsochromic to bathochromic shift. All the compounds displayed remarkable photo-luminescent properties and various maximum emission peaks owing to the different nature of the functional groups. Furthermore, the anti-microbial potential of ligands and complexes was evaluated with docking analyses carried out to investigate the binding affinity of terpyridine-based ligands along with corresponding proteins (shikimate dehydrogenase and penicillin-binding protein) binding sites. To obtain further insight into molecular orbital distributions and spectroscopic properties, density functional theory calculations were performed for representative complexes. The photophysical activity and interactions between chromophore structure and properties were both investigated experimentally as well as theoretically.
Shearlets as feature extractor for semantic edge detection: the model-based and data-driven realm
Authors: Andrade-Loarca Héctor , Kutyniok Gitta , Öktem Ozan
Published: November 2020

Semantic edge detection has recently gained a lot of attention as an image-processing task, mainly because of its wide range of real-world applications. This is based on the fact that edges in images contain most of the semantic information. Semantic edge detection involves two tasks, namely pure edge detection and edge classification. Those are in fact fundamentally distinct in terms of the level of abstraction that each task requires. This fact is known as the distracted supervision paradox and limits the possible performance of a supervised model in semantic edge detection. In this work, we will present a novel hybrid method that is based on a combination of the model-based concept of shearlets, which provides probably optimally sparse approximations of a model class of images, and the data-driven method of a suitably designed convolutional neural network. We show that it avoids the distracted supervision paradox and achieves high performance in semantic edge detection. In addition, our approach requires significantly fewer parameters than a pure data-driven approach. Finally, we present several applications such as tomographic reconstruction and show that our approach significantly outperforms former methods, thereby also indicating the value of such hybrid methods for biomedical imaging.
Foraging behaviour alters with social environment in a juvenile songbird
Authors: Franks Victoria R. , Ewen John G. , McCready Mhairi , Thorogood Rose
Published: November 2020

Early independence from parents is a critical period where social information acquired vertically may become outdated, or conflict with new information. However, across natural populations, it is unclear if newly independent young persist in using information from parents, or if group-level effects of conformity override previous behaviours. Here, we test if wild juvenile hihi (
Notiomystis cincta
, a New Zealand passerine) retain a foraging behaviour from parents, or if they change in response to the behaviour of peers. We provided feeding stations to parents during chick-rearing to seed alternative access routes, and then tracked their offspring's behaviour. Once independent, juveniles formed mixed-treatment social groups, where they did not retain preferences from their time with parents. Instead, juvenile groups converged over time to use one access route­ per group, and juveniles that moved between groups switched to copy the locally favoured option. Juvenile hihi did not copy specific individuals, even if they were more familiar with the preceding bird. Our study shows that early social experiences with parents affect initial foraging decisions, but social environments encountered later on can update transmission of arbitrary behaviours. This suggests that conformity may be widespread in animal groups, with potential cultural, ecological and evolutionary consequences.
Maternally derived anti-helminth antibodies predict offspring survival in a wild mammal
Authors: Sparks Alexandra M. , Hayward Adam D. , Watt Kathryn , Pilkington Jill G. , Pemberton Josephine M. , Johnston Susan E. , McNeilly Tom N. , Nussey Daniel H.
Published: November 2020

The transfer of antibodies from mother to offspring provides crucial protection against infection to offspring during early life in humans and domestic and laboratory animals. However, few studies have tested the consequences of variation in maternal antibody transfer for offspring fitness in the wild. Further, separating the immunoprotective effects of antibodies from their association with nutritional resources provided by mothers is difficult. Here, we measured plasma levels of total and parasite-specific antibodies in neonatal (less than 10 days old) wild Soay sheep over 25 years to quantify variation in maternal antibody transfer and test its association with offspring survival. Maternal antibody transfer was predicted by maternal age and previous antibody responses, and was consistent within mothers across years. Neonatal total IgG antibody levels were positively related to early growth, suggesting they reflected nutritional transfer. Neonatal parasite-specific IgG levels positively predicted first-year survival, independent of lamb weight, total IgG levels and subsequent lamb parasite-specific antibody levels. This relationship was partly mediated via an indirect negative association with parasite burden. We show that among-female variation in maternal antibody transfer can have long-term effects on offspring growth, parasite burden and fitness in the wild, and is likely to impact naturally occurring host–parasite dynamics.
Last-come, best served? Mosquito biting order and
Plasmodium
transmission
Authors: Isaïa J. , Rivero A. , Glaizot O. , Christe P. , Pigeault R.
Published: November 2020

A pervasive characteristic of parasite infections is their tendency to be overdispersed. Understanding the mechanisms underlying this overdispersed distribution is of key importance as it may impact the transmission dynamics of the pathogen. Although multiple factors ranging from environmental stochasticity to inter-individual heterogeneity may explain parasite overdispersion, parasite infection is also overdispersed in an inbred host population maintained under laboratory conditions, suggesting that other mechanisms are at play. Here, we show that the aggregated distribution of malaria parasites within mosquito vectors is partially explained by a temporal heterogeneity in parasite infectivity triggered by the bites of mosquitoes. Parasite transmission tripled between the mosquito's first and last blood feed in a period of only 3 h. Surprisingly, the increase in transmission is not associated with an increase in parasite investment in production of the transmissible stage. Overall, we highlight that
Plasmodium
is capable of responding to the bites of mosquitoes to increase its own transmission at a much faster pace than initially thought and that this is partly responsible for overdispersed distribution of infection. We discuss the underlying mechanisms as well as the broader implications of this plastic response for the epidemiology of malaria.
Use of Artificial Intelligence on spatio-temporal data to generate insights during COVID-19 pandemic: A Review
Authors: Jayatilaka Gihan , Hassan Jameel , Marikkar Umar , Perera Rumali , Sritharan Suren , Weligampola Harshana , Ekanayake Mevan , Godaliyadda Roshan , Ekanayake Parakrama , Herath Vijitha , Dilshan Godaliyadda G M , Rathnayake Anuruddhika , Dharmaratne Samath D. , Ekanayake Janaka
Published: November 2020

The COVID-19 pandemic, within a short time span, has had a significant impact on every aspect of life in almost every country on the planet. As it evolved from a local epidemic isolated to certain regions of China, to the deadliest pandemic since the influenza outbreak of 1918, scientists all over the world have only amplified their efforts to combat it. In that battle, Artificial Intelligence, or AI, with its wide ranging capabilities and versatility, has played a vital role and thus has had a sizable impact. In this review, we present a comprehensive analysis of the use of AI techniques for spatio-temporal modeling and forecasting and impact modeling on diverse populations as it relates to COVID-19. Furthermore, we catalogue the articles in these areas based on spatio-temporal modeling, intrinsic parameters, extrinsic parameters, dynamic parameters and multivariate inputs (to ascertain the penetration of AI usage in each sub area). The manner in which AI is used and the associated techniques utilized vary for each body of work. Majority of articles use deep learning models, compartment models, stochastic methods and numerous statistical methods. We conclude by listing potential paths of research for which AI based techniques can be used for greater impact in tackling the pandemic.
Disaggregating Asian Race Reveals COVID-19 Disparities among Asian Americans at New York City’s Public Hospital System
Authors: Marcello Roopa Kalyanaraman , Dolle Johanna , Tariq Areeba , Kaur Sharanjit , Wong Linda , Curcio Joan , Thachil Rosy , Yi Stella S. , Islam Nadia
Published: November 2020

There is growing recognition of the burden of COVID-19 among Asian Americans, but data on outcomes among Asian ethnic subgroups remain extremely limited. We conducted a retrospective analysis of 85,328 patients tested for COVID-19 at New York City’s public hospital system between March 1 and May 31, 2020, to describe characteristics and COVID-19 outcomes of Asian ethnic subgroups compared to Asians overall and other racial/ethnic groups. South Asians had the highest rates of positivity and hospitalization among Asians, second only to Hispanics for positivity and Blacks for hospitalization. Chinese patients had the highest mortality rate of all groups and were nearly 1.5 times more likely to die than Whites. The high burden of COVID-19 among South Asian and Chinese Americans underscores the urgent needs for improved data collection and reporting as well as public health program and policy efforts to mitigate the disparate impact of COVID-19 among these communities.
EXPLORING HIGH MORTALITY RATES AMONG PEOPLE WITH MULTIPLE AND COMPLEX NEEDS: A QUALITATIVE STUDY USING PEER RESEARCH METHODS
Authors: Perry Rachel , Adams Emma A. , Harland Jill , Broadbridge Angela , Giles Emma L. , McGeechan Grant J. , O’Donnell Amy , Ramsay Sheena E.
Published: November 2020

Objective

To explore the reasons underlying high mortality rates among people with multiple and complex needs and potential preventive opportunities.

Design

Qualitative study using peer research

Setting

North East of England

Participants

Three focus group discussions were held involving: 1) people with lived experience of MCN (n=5); 2) frontline staff from health, social care, and voluntary organisations that support MCN groups (n=7); and 3) managers and commissioners of these organisations (n=9).

Results

Findings from this study provide valuable insights from people with lived experience and staff on the complexity underpinning high mortality rates for individuals experiencing multiple and complex needs. Mental ill-health and substance misuse (often co-occurring dual diagnosis) were highlighted as significant factors underlying premature mortality among multiple and complex needs groups. Potential triggers to identify people at-risk included critical life events (e.g. bereavement, relationship breakdown) and transitions (e.g. release from prison, completion of drug treatment). Early prevention, particularly supporting young people experiencing adverse childhood experiences was also highlighted as a priority.

Conclusion

High mortality in MCN groups may be reduced by addressing dual diagnosis, providing more support at critical life events, and investing in early prevention efforts. Future service delivery should take into consideration the intricate nature of multiple and complex needs and improve service access and navigation.

ARTICLE SUMMARY

Strengths and limitations of this study

This study employed focus group discussions with individuals with multiple and complex needs and service providers to understand the complexity underpinning high morality rates for individuals experiencing multiple and complex needs.

Peer researchers contributed to all stages of this study, including developing the aims, data collection, interpretation, and shaping recommendations.

Using peer researchers enhanced our access to participants and improved interpretation of data

The main limitation is that the study only recruited individuals in one region in the North East of England. Views from individuals with MCN and service providers in other areas of England might have led the results to being more generalisable.
Excess Dietary Fructose Does Not Alter Gut Microbiota or Permeability in Humans: A Randomized Controlled Pilot Study
Authors: Aleman Jose O. , Henderson Wendy A. , Walker Jeanne M. , Ronning Andrea , Jones Drew , Walter Peter J. , Daniel Scott G. , Bittinger Kyle , Vaughan Roger , MacArthur Robert , Chen Kun , Breslow Jan L. , Holt Peter R.
Published: November 2020

Background and Aims

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease that accompanies obesity and the metabolic syndrome. Excess fructose consumption can initiate or exacerbate NAFLD due in part to a consequence of impaired hepatic fructose metabolism. Pre-clinical data have emphasized that fructose-induced altered gut microbiome, increased gut permeability, and endotoxemia play an important role in NAFLD, but human studies are sparse. The present study aimed to explore the relevance of these pre-clinical studies to observations in humans.

Methods

We performed a classical double-blind metabolic unit study in 10 obese subjects (BMI 30-40 mg/kg/m2) providing 75gms. of either fructose or glucose in their individual diets substituted isocalorically for complex carbohydrates in a cross-over study. Excess fructose intake was provided in the fructose arm of the study and totaled a mean of 22.7% of calories.

Results

Routine blood, uric acid, liver function and lipid measurements were unaffected by the fructose intervention. The fecal microbiome (includingAkkermansia muciniphilia), fecal metabolites, gut permeability, indices of endotoxemia, gut damage or inflammation and plasma metabolites were essentially unchanged by either intervention.

Conclusions

Although pre-clinical rodent studies have shown that excess fructose causes pronounced changes in the gut microbiome, metabolome, and permeability as well as endotoxemia, this did not occur in obese individuals fed fructose in amounts known to enhance NAFLD. Therapeutic efforts to improve NAFLD through changes in the gut microbiome and gut homeostasis may not be beneficial.
DEFINING CANDIDATE PARKINSON’S DISEASE GENES THROUGH THE ANALYSIS OF GENOME-WIDE HOMOZYGOSITY
Authors: Lubbe Steven J , Wong Yvette C. , Bustos Bernabe , Kim Soojin , Vandrovcova Jana , Norman Brendan P , Tan Manuela , Murphy David , Carroll Camille B , Grosset Donald , Ryten Mina , Botía Juan A. , Escott-Price Valentina , Williams Nigel M , Krainc Dimitri , Morris Huw R ,   for International Parkinson’s Disease Genomics Consortium
Published: November 2020

Early-onset Parkinson’s disease (EOPD) can be caused by biallelic mutations in PRKN, DJ1 and PINK1. However, while the identification of novel genes is becoming increasingly challenging, new insights into EOPD genetics have important relevance for understanding the pathways driving disease pathogenesis. Here, using extended runs of homozygosity (ROH) >8Mb as a marker for possible autosomal recessive inheritance, we identified 90 EOPD patients with extended ROH. Investigating rare, damaging homozygous variants to identify candidate genes for EOPD, 81 genes were prioritised. Through the assessment of biallelic (homozygous and compound heterozygous) variant frequencies in cases and controls from three independent cohorts totalling 3,381 PD patients and 2,463 controls, we identified two biallelic MIEF1 variant carriers among EOPD patients. We further investigated the role of disease-associated variants in MIEF1 which encodes for MID51, an outer mitochondrial membrane protein, and found that putative EOPD-associated variants in MID51 preferentially disrupted its oligomerization state. These findings provide further support for the role of mitochondrial dysfunction in the development of PD. Together, we have used genome-wide homozygosity mapping to identify potential EOPD genes, and future studies incorporating expanded datasets and further functional analyses will help to determine their roles in disease aetiology.
Identifying bias in models that detect vocal fold paralysis from audio recordings using explainable machine learning and clinician ratings
Authors: Low Daniel M. , Rao Vishwanatha , Randolph Gregory , Song Phillip C. , Ghosh Satrajit S.
Published: November 2020

Introduction

Detecting voice disorders from voice recordings could allow for frequent, remote, and low-cost screening before costly clinical visits and a more invasive laryngoscopy examination. Our goals were to detect unilateral vocal fold paralysis (UVFP) from voice recordings using machine learning, to identify which acoustic variables were important for prediction to increase trust, and to determine model performance relative to clinician performance.

Methods

Patients with confirmed UVFP through endoscopic examination (N=77) and controls with normal voices matched for age and sex (N=77) were included. Voice samples were elicited by reading the Rainbow Passage and sustaining phonation of the vowel “a”. Four machine learning models of differing complexity were used. SHapley Additive exPlanations (SHAP) was used to identify important features.

Results

The highest median bootstrapped ROC AUC score was 0.87 and beat clinician’s performance (range: 0.74 – 0.81) based on the recordings. Recording durations were different between UVFP recordings and controls due to how that data was originally processed when storing, which we can show can classify both groups. And counterintuitively, many UVFP recordings had higher intensity than controls, when UVFP patients tend to have weaker voices, revealing a dataset-specific bias which we mitigate in an additional analysis.

Conclusion

We demonstrate that recording biases in audio duration and intensity created dataset-specific differences between patients and controls, which models used to improve classification. Furthermore, clinician’s ratings provide further evidence that patients were over-projecting their voices and being recorded at a higher amplitude signal than controls. Interestingly, after matching audio duration and removing variables associated with intensity in order to mitigate the biases, the models were able to achieve a similar high performance. We provide a set of recommendations to avoid bias when building and evaluating machine learning models for screening in laryngology.
A comparative study of real-time RT-PCR based SARS-CoV-2 detection methods and its application to human derived and surface swabbed material
Authors: Tastanova Aizhan , Stoffel Corinne Isabelle , Dzung Andreas , Cheng Phil Fang , Bellini Elisa , Johansen Pål , Duda Agathe , Nobbe Stephan , Lienhard Reto , Bosshard Philipp Peter , Levesque Mitchell Paul
Published: November 2020

Real-time reverse transcription polymerase chain reaction (RT-PCR) remains a gold standard in detection of various viral diseases. In the COVID-19 pandemic, multiple RT-PCR based tests were developed to screen for viral infection. As an emergency response to growing testing demand, we established a SARS-CoV-2 PCR diagnostics platform for which we compared different commercial and in-house RT-PCR protocols. We evaluated four commercial (CDC 2019-nCoV, Applied Biosystems™ 2019-nCoV Assay Kit v1 TF-SinglePlex, 2019-nCoV Assay Kit v2 TF-MultiPlex, and EURORealTime SARS-CoV-2), one customized (Institute Pasteur), and one in-house RT-PCR protocols with 92 SARS-CoV-2 positive and 92 SARS-CoV-2 negative samples. Furthermore, we compared economical and practical characteristics of these protocols. We also developed a highly sensitive digital droplet PCR (ddPCR) method. Finally, we conducted a local environmental study for the presence and infectivity of SARS-CoV-2 on different surfaces in a quarantined household using RT- and ddPCR methods. We found very low limits of detection (1 or 2 viral copies/μL), high sensitivities (93.6-97.8%) and specificities (98.7-100%) for the tested RT-PCR protocols. We further demonstrated the feasibility of downscaling two of the commercial protocols, which could optimize testing capacity. In the local environmental study, only one surface sample tested positive for viral RNA, but without detectable infectivity in vitro. Tested commercial and customized RT-PCR detection kits show very good and comparable sensitivity, and specificity, and the kits could be further optimized for use on SARS-CoV-2 viral samples derived from human and surface swabbed samples.
Statistical Analyses of the Public Health and Economic Performance of Nordic Countries in Response to the COVID-19 Pandemic
Authors: Gordon Daniel V. , Grafton R. Quentin , Steinshamn Stein Ivar
Published: November 2020

Aim

To compare trends and undertake statistical analyses of differences in public health performance (confirmed cases and fatalities) of Nordic countries; Denmark, Finland, Norway and Sweden, and New Zealand, in response to the COVID-19 pandemic.

Methods

Per capita trends in total cases and per capita fatalities were analysed and difference-in-difference statistical tests undertaken to assess whether differences in stringency of mandated social distancing (SD) measures, testing rates and border closures explain cross-country differences.

Results

Sweden is a statistical outlier, relative to its Nordic neighbours, for both per capita cases and per capita fatalities associated with COVID-19 but not in terms of the reduction in economic growth. Sweden’s public health differences, compared to its Nordic neigbours, are partially explained by differences in terms of international border closures and the level of stringency of SD measures (including testing) implemented from early March to June 2020.

Conclusions

We find that: one, early imposition of full international travel restrictions combined with high levels of government-mandated stringency of SD reduced the per capita cases and per capita fatalities associated with COVID-19 in 2020 in the selected countries and, two, in Nordic countries, less stringent government-mandated SD is not associated with higher quarterly economic growth.
Perceived mental health, wellbeing and associated factors among Nepali migrant and non-migrant workers: A qualitative study
Authors: Devkota Hridaya Raj , Bhandari Bishnu , Adhikary Pratik
Published: November 2020

Background

Poor mental health and illness among the working population have serious socio-economic and public health consequences for both the individual and society/country. With a dramatic increase in work migration over the past decades, there is recent concern about the health and wellbeing of migrant workers and their accessibility to healthcare services in destination countries. This study aimed to explore the mental health and wellbeing experiences of Nepali returnee-migrants and non-migrant workers, and identify their perception on the risk factors for poor health and health service accessibility for them.

Methods

This qualitative study was conducted among Nepali migrant and non-migrant workers in February 2020. Four focus group discussions (n=25) and 15 in-depth interviews were conducted with male non-migrant and returnee migrant workers from Gulf countries and Malaysia. The discussions and interviews were audio-recorded, transcribed, translated into English and analysed thematically.

Result

Migrant workers reported a higher risk of developing adverse mental health conditions than non-migrant workers. In addition, fever, upper respiratory infection, abdominal pain, ulcer, and occupational injuries were common health problems among both migrant and non-migrant workers. Other major illnesses reported by the migrant workers were heat burns and rashes, snake-bites, dengue, malaria, gallstone, kidney failure, and sexually transmitted diseases, while non-migrants reported hypertension, diabetes, and heart diseases. Adverse living and working conditions including exploitation and abuse by employers, lack of privacy and congested accommodation, language barriers, long hours’ hard physical work without breaks, and unhealthy lifestyles were the contributing factors to migrant workers’ poor mental and physical health. Both migrant and non-migrants reported poor compliance of job conditions and labor protection by their employers such as application of safety measures at work, provision of insurance and healthcare facilities that affected for their wellbeing negatively. Family problems compounded by constant financial burdens and unmet expectations were the most important factors linked with migrant workers’ poor mental health condition.

Conclusion

Both migrant and non-migrant workers experienced poor mental and physical health condition largely affected by their adverse living and working conditions, unmet familial and financial needs and adherence to unhealthy life styles. It is needed to ensure the compliance of work agreement by employers and promotion of labor rights in relation to worker’s health and safety. In addition, policy interventions on raising awareness on occupational health risk and effective safety training to all migrant and non-migrant workers are recommended.
Deciphering early-warning signals of SARS-CoV-2 elimination and resurgence from limited data at multiple scales
Authors: Parag Kris V , Cowling Benjamin J , Donnelly Christl A
Published: November 2020

Inferring the transmission potential of an infectious disease during low-incidence periods following epidemic waves is crucial for preparedness. In such periods, scarce data may hinder existing inference methods, blurring early-warning signals essential for discriminating between the likelihoods of resurgence versus elimination. Advanced insight into whether elevating caseloads (requiring swift community-wide interventions) or local elimination (allowing controls to be relaxed or refocussed on case-importation) might occur, can separate decisive from ineffective policy. By generalising and fusing recent approaches, we propose a novel early-warning framework that maximises the information extracted from low-incidence data to robustly infer the chances of sustained local-transmission or elimination in real time, at any scale of investigation (assuming sufficiently good surveillance). Applying this framework, we decipher hidden disease-transmission signals in prolonged low-incidence COVID-19 data from New Zealand, Hong Kong and Victoria, Australia. We uncover how timely interventions associate with averting resurgent waves, support official elimination declarations and evidence the effectiveness of the rapid, adaptive COVID-19 responses employed in these regions.
A simple, effective enclosure with disposable coverings for inexpensive containment of aerosolized COVID viruses during tracheal intubation and extubation
Authors: Monroe Luke W. , Johnson Jack S. , Gutstein Howard B. , Lawrence John P. , Lejeune Keith , Sullivan Ryan C. , Jen Coty N.
Published: November 2020

Structured Abstract

Background

SARS-CoV-2 (COVID-19) is a severe respiratory virus that can be transmitted through aerosol particles produced by coughing, talking, and breathing. Medical procedures used to treat severe cases such as tracheal intubation, extubation, and tracheal suctioning produce infectious aerosol particles. This presents significant risk for viral exposure of nearby healthcare workers during and following tracheal operations. This study looks at an enclosure to limit medical personnel’s exposure to these particles.

Methods

A low-cost plastic enclosure was designed to reduce aerosol spread and viral transmission during intubation and extubation procedures. The enclosure consists of clear polycarbonate for maximum visibility. Large side cutouts provide health care providers with ease of access to the patient. Aerosol particle instruments measured the aerosol containment efficacy after applying various types of plastic coverings to seal the side openings. The use of negative pressure was also tested.

Results

The enclosure with 2 layers of plastic coverings sealing the side openings reduced total escaped particle number concentrations (diameter > 0.01 μm) by over 93% at 3 inches away from all openings. Concentration decay experiments indicated that the enclosure without active suction should be left on the patient for 15-20 minutes following a tracheal manipulation to allow sufficient time for >90% of aerosol particles to settle upon interior surfaces. This decreases to 5 minutes when 30 LPM suction is applied.

Conclusions

This enclosure is an inexpensive, easily implemented additional layer of protection that can be used to reduce the risk of SARS-CoV-2 aerosol transmission between patients and healthcare workers.
Association of antihypertensive agents with the risk of in-hospital death in patients with Covid-19
Authors: Chouchana Laurent , Beeker Nathanaël , Garcelon Nicolas , Rance Bastien , Paris Nicolas , Salamanca Elisa , Polard Elisabeth , Burgun Anita , Treluyer Jean-Marc , Neuraz Antoine
Published: November 2020

In this retrospective multicenter cohort study, we aimed to investigate the association between antihypertensive agent exposure and in-hospital mortality in patients with Covid-19. Of 8,078 hospitalized patients for Covid-19, 3,686 (45.6%) had hypertension including 2043 (55.4%) patients exposed to a renin-angiotensin-aldosterone inhibitors (RAASi), 1624 (44.1%) to calcium channel blockers (CCB) and 1154 (37.7%) to beta-blockers. Overall in-hospital 30-day mortality was 23.1%. Compared to non-users, the risk of mortality was lower in CCB (aOR, 0.83 [0.70-0.99]) and beta-blockers users (aOR, 0.80 [0.67-0.95]), and not different in RAASi users. These findings support the continuation of antihypertensive agents in patients with Covid-19.
Fever temperatures impair hemolysis caused by strains ofEscherichia coliandStaphylococcus aureus
Authors: Palela Mihaela , Giol Elena Diana , Amzuta Andreia , Ologu Oxana G. , Stan Razvan C.
Published: November 2020

Hemolysis modulates susceptibility to bacterial infections and predicts poor sepsis outcome. Hemolytic bacteria induce upon infection a reversible fever response from the host that may aid in pathogen clearance. To delineate the role of fever temperatures on the growth and infectivity of two hemolytic bacteria that are known to evoke fever in patients via hemotoxins, we used high-sensitivity microcalorimetry to measure the evolution of heat production by fever-inducing strains ofEscherichia coliandStaphylococcus aureusunder fever conditions. We determined specific aggregation profiles at temperatures equal to or exceeding 38.5□. We confirmed these results through bacterial incubation at relevant temperatures revealing the presence or absence of hemolysis. We thus reveal an additional positive role of febrile temperatures in directly contributing to the immune response, through the abolishment of hemolysis.
PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells
Authors: Grasmann Gabriele , Planque Mélanie , Madreiter-Sokolowski Corina T. , Hrzenjak Andelko , Graier Wolfgang F. , Fendt Sarah-Maria , Olschewski Horst , Leithner Katharina
Published: November 2020

Cancer cells frequently lack nutrients like glucose, due to insufficient vascular networks. A decrease of extracellular glucose is accompanied by enhanced mitochondrial respiration in cancer cells, which promotes the formation of potentially harmful reactive oxygen species (ROS). Here we show that a gluconeogenesis enzyme, mitochondrial phosphoenolpyruvate carboxykinase, PCK2, acts as a regulator of mitochondrial respiration and maintains the redox balance in nutrient-deprived lung cancer cells. PCK2 silencing increased the abundance and interconversion of tricarboxylic acid (TCA) cycle intermediates, augmented mitochondrial respiration and enhanced glutathione oxidation under glucose and serum starvation, in a PCK2 re-expression reversible manner. Moreover, augmenting the TCA cycle by PCK2 inhibition severely reduced colony formation. As a conclusion, PCK2 contributes to maintaining a reduced glutathione pool upon starvation besides mediating the biosynthesis of gluconeogenic/glycolytic intermediates. The study sheds light on adaptive responses in cancer cells to nutrient deprivation and identifies gluconeogenesis as starvation-induced pathway that limits respiration-induced oxidative stress.
The role of SOX9 in non-small cell lung cancer progression is histopathology-selective
Authors: Bao Jie , Närhi Katja , Teodòsio Ana , Hemmes Annabrita , Linnavirta Nora M , Mäyränpää Mikko I , Salmenkivi Kaisa , Quesne John Le , Verschuren Emmy W
Published: November 2020

The transcription factor SOX9 is a key regulator of multiple developmental processes, and is frequently re-expressed in non-small cell lung cancer (NSCLC). Its precise role in the progression of NSCLC histopathologies has however remained elusive. We show that SOX9 expression relates to poor outcome and invasive histopathology in human adenocarcinomas, and is absent in murine early minimally invasive and humanin situadenocarcinoma. Interestingly, despite wide SOX9 expression across advanced NSCLC histotypes, its genetic deletion in the murineKrasG12D;Lkb1-/-model selectively disrupted only the growth of papillary NSCLC, without affecting the initiation of precursor lesions or growth of mucinous or squamous tissue. Spatial tissue phenotyping indicated a requirement of SOX9 expression for the progression of surfactant protein C-expressing progenitor cells, which gave rise to papillary tumours. Intriguingly, while SOX9 expression was dispensable for squamous tissue formation, its loss in fact led to enhanced squamous tumour metastasis, which was associated with altered collagen IV deposition in the basement membrane. Our work therefore demonstrates histopathology-selective roles for SOX9 in NSCLC progression, namely a requirement for papillary adenocarcinoma progression, but opposing metastasis-suppressing function in squamous histotype tissue. This attests to a pleiotropic SOX9 function, linked to the cell of origin and microenvironmental tissue contexts.
Exploring and illustrating the mouse embryo: virtual objects to think and create with
Authors: Vianello Stefano
Published: November 2020

The teaching, learning, communication, and practice of Developmental Biology require interested parties to be at ease with the considerable spatial complexity of the embryo, and with its evolution over time as it undergoes morphogenesis. In practice, the four dimensionality of embryonic development (space and time) calls upon strong visual-spatial literacy and mental manipulation skills, generally expected to be innate or to come through experience. Yet it has been argued that Developmental Biology suffers the most from available traditional media of communication and representation. To date, few resources exist to engage with the embryo in its 3D and 4D aspects, to communicate such aspects in one’s work, and to facilitate their exploration in the absence of live observations. I here provide a collection of readily-usable volumetric models for all tissues and stages of mouse peri-implantation development as extracted from the eMouse Atlas Project (E5.0 to E9.0), as well as custom-made models of all pre-implantation stages (E0 to E4.0). These models have been converted to a commonly used 3D format (.stl), and are provided in ready-made files for digital exploration and illustration. Further provided is a step-by-step walkthrough on how to practically use these models for exploration and illustration using the free and open source 3D creation suite Blender. I finally outline possible further uses of these very models in outreach initiatives of varying levels, virtual and augmented reality applications, and 3D printing.
SEPIA: Simulation-based Evaluation of Prioritization Algorithms
Authors: Almaraz Kimberly , Jang Tyler , Lewis McKenna , Ngo Titan , Song Miranda , Moshiri Niema
Published: November 2020

Background

The ability to prioritize people living with HIV by risk of future transmissions could aid public health officials in optimizing epidemiological intervention. While methods exist to perform such prioritization based on molecular data, their effectiveness and accuracy are poorly understood, and it is unclear how one can directly compare the accuracy of different methods. We introduce SEPIA (Simulation-based Evaluation of PrIoritization Algorithms), a novel simulation-based framework for determining the effectiveness of prioritization algorithms. Under several metrics of effectiveness that we propose, we utilize various properties of the simulated contact networks and transmission histories to compare existing prioritization approaches: one phylogenetic (ProACT) and one distance-based (growth of HIV-TRACE transmission clusters).

Results

Using all metrics of effectiveness that we propose, ProACT consistently slightly outperformed the transmission cluster growth approach. However, both methods consistently performed just marginally better than random, suggesting that there is significant room for improvement in prioritization tools.

Conclusion

We hope that, by providing ways to quantify the effectiveness of prioritization methods in simulation, SEPIA will aid researchers in developing novel tools for prioritizing people living with HIV by risk of future transmissions.
Predicting perturbation effects from resting activity using functional causal flow
Authors: Nejatbakhsh Amin , Fumarola Francesco , Esteki Saleh , Toyoizumi Taro , Kiani Roozbeh , Mazzucato Luca
Published: November 2020

A crucial challenge in targeted manipulation of neural activity is to identify perturbation sites whose stimulation exerts significant effects downstream (high efficacy), a procedure currently achieved by labor-intensive trial-and-error. Targeted perturbations will be greatly facilitated by understanding causal interactions within neural ensembles and predicting the efficacy of perturbation sites before intervention. Here, we address this issue by developing a computational framework to predict how single-site micorstimulation alters the ensemble spiking activity in an alert monkey’s prefrontal cortex. Our framework uses delay embedding techniques to infer the ensemble’s functional causal flow (FCF) based on the functional interactions inferred at rest. We validate FCF using ground truth data from models of cortical circuits, showing that FCF is robust to noise and can be inferred from brief recordings of even a small fraction of neurons in the circuit. A detailed comparison of FCF with several alternative methods, including Granger causality and transfer entropy, highlighted the advantages of FCF in predicting perturbation effects on empirical data. Our results provide the foundation for using targeted circuit manipulations to develop targeted interventions suitable for brain-machine interfaces and ameliorating cognitive dysfunctions in the human brain.
Micronuclei arising due to loss of KIF18A form stable micronuclear envelopes and do not promote tumorigenesis
Authors: Sepaniac Leslie A. , Martin Whitney , Dionne Louise A. , Stearns Timothy M. , Reinholdt Laura G. , Stumpff Jason
Published: November 2020

Micronuclei, whole or fragmented chromosomes which are spatially separated from the main nucleus, are strongly associated with genomic instability and have been identified as drivers of tumorigenesis. Paradoxically,Kif18amutant mice produce micronuclei due to unaligned chromosomesin vivobut do not develop spontaneous tumors, raising questions about whether all micronuclei contribute similarly to genomic instability and cancer. We report here that micronuclei inKif18amutant mice form stable nuclear envelopes. ChallengingKif18amutant mice via deletion of theTrp53gene led to formation of thymic lymphoma with elevated levels of micronuclei. However, loss ofKif18ahad modest or no effect on survival ofTrp53homozygotes and heterozygotes, respectively. To further explore micronuclear envelope stability inKIF18AKO cells, we compared micronuclei induced via different insults in cultured cells. Micronuclei inKIF18AKO cells form stable nuclear envelopes characterized by increased recruitment of core and non-core nuclear envelope components and successful expansion of decondensing chromatin compared to those induced by microtubule drug washout or exposure to radiation. We also observed that lagging chromosomes, which lead to micronucleus formation, were positioned closer to the main chromatin masses, and further from the central spindle, inKIF18AKO cells. Our studies providein vivosupport to models suggesting that micronuclear fate depends on the sub-cellular location of late lagging chromosomes and suggest that not all micronuclei actively promote tumorigenesis.