bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Dose Whole-Lung Radiation for COVID-19 Pneumonia: Planned Day-7 Interim Analysis of an Ongoing Clinical Trial
Authors: Hess Clayton B. , Buchwald Zachary S. , Stokes William , Switchenko Jeffrey M. , Nasti Tahseen H. , Weinberg Brent D. , Steinberg James P. , Godette Karen D. , Murphy David , Ahmed Rafi , Curran Walter J. , Khan Mohammad K.
Published: June 2020

Background

Individuals with advanced age and comorbidities face higher risk of death from COVID-19, especially once ventilator-dependent. Respiratory decline in COVID-19 is mediated by a pneumonic aberrant immune cytokine storm. Low-dose radiation was used to treat pneumonia in the pre-antibiotic era. Radiation immunomodulatory effects may improve outcomes in COVID-19.

Methods

We performed a single-institution phase I/II trial evaluating the safety and efficacy of single-fraction, low-dose, whole-lung radiation for COVID-19 pneumonia. Eligible patients were hospitalized, had radiographic pneumonic infiltrates, required supplemental oxygen, and were clinically deteriorating.

Results

Of nine patients screened, five were treated with whole-lung radiation from April 2328, 2020 and followed for 7 days. Median age was 90 (range 64-94); four were nursing home residents with multiple comorbidities. Within 24 hours of radiation, three patients (60%) weaned from supplemental oxygen to ambient air, four (80%) exhibited radiographic improvement, and median Glasgow coma score improved from 10 to 14. A fourth patient (80% overall recovery) weaned from oxygen at hour 96. Mean time to clinical recovery was 35 hours. There were no acute skin, pulmonary, GI, GU toxicities.

Conclusions

In a small pilot trial of five oxygen-dependent patients with COVID-19 pneumonia, low-dose whole-lung radiation led to rapid improvement in clinical status, encephalopathy, and radiographic infiltrates without acute toxicity or worsening the cytokine storm. Low-dose whole-lung radiation appears to be safe, shows early promise of efficacy, and warrants larger prospective trials.

Lay Summary

Researchers at Emory University have completed treatment of cohort 1 of a pilot trial of low-dose lung irradiation for COVID-19 pneumonia. Five residents of nursing or group homes with COVID-19 outbreaks were hospitalized after testing positive for COVID-19. Each had pneumonia visible on chest x-ray, required supplemental oxygen, and had clinically declined. A single treatment of low-dose (1.5 Gy) radiation to both lungs was delivered over 10-15 minutes. Within 24 hours, four patients rapidly improved their breathing, recovering at an average of 1.5 days (range 3 to 96 hours), and had either been discharged (three) or were preparing for discharge (one) by day 14. Blood tests and repeat imaging confirmed that low-dose radiation appeared safe and effective in reducing their COVID-19 symptoms. Further trials are warranted.
High Liver Fat Associates with Higher Risk of Developing Symptomatic COVID-19 Infection - Initial UK Biobank Observations
Authors: Roca-Fernández A , Dennis A , Nicolls R , McGonigle J , Kelly M , Banerjee R
Published: June 2020

Background

A high proportion of COVID-19 patients develop acute liver dysfunction. Early research has suggested that pre-existing fatty liver disease may be a significant risk factor for hospitalisation. Liver fat, in particular, is a modifiable parameter and can be a target for public health policy and individual patient plans. In this study we aimed to assess pre-existing liver disease as a risk factor for developing symptomatic COVID-19.

Methods

From 502,506 participants from the UK Biobank, 42,146 underwent MRI (aged 45–82), and had measures of liver fat, liver fibroinflammatory disease and liver iron. Patients were censored on May 28th to determine how many had tested for COVID-19 with symptomatic disease. UK testing was restricted to those with symptoms in hospital. COVID-19 symptoms included fever, dry cough, sore throat, diarrhoea and fatigue. Univariate analysis was performed on liver phenotypic biomarkers to determine if these variables increased risk of symptomatic COVID-19, and compared to previously described risk factors associated with severe COVID-19, including to age, ethnicity, gender and obesity,

Findings

Increased liver fat was associated with a higher risk for symptomatic confirmed COVID-19 in this population in univariate analysis(OR:1.85, p = 0.03). In obese participants, only those with concomitant fatty liver(≥10%) were at increased risk(OR:2.96, p = 0.02), with those having normal liver fat (< 5%) showing no increased risk(OR:0.36, p = 0.09).

Conclusions

UK Biobank data demonstrated an association between pre-existing liver disease and obesity with severe COVID-19, with higher proportions of liver fat in obese individuals a likely risk factor for symptomatic disease and severity.

Public policy measures to protect patients with liver disease who may have almost double the risk of the general population should be considered, especially as dietary and pharmacological strategies to reduce body weight and liver fat already exist.

Funding

University of Oxford, Innovate UK, UK Biobank. Authors are employees of Perspectum Ltd.
Adverse effects of COVID-19 related lockdown on pain, physical activity and psychological wellbeing in people with chronic pain
Authors: Fallon Nicholas , Brown Christopher , Twiddy Hannah , Brian Eleanor , Frank Bernhard , Nurmikko Turo , Stancak Andrej
Published: June 2020

Countries across the world imposed lockdown restrictions during the COVID-19 pandemic. It has been proposed that lockdown conditions disproportionately impact those living with chronic pain, requiring adaptation to treatment and care strategies. We investigated how lockdown restrictions in the United Kingdom impacted individuals with chronic pain (N = 431) relative to a healthy control group (N = 88) using an online survey. In accordance with the fear-avoidance model, we hypothesised increases in perceived pain and psychological distress that would be mediated by pain catastrophizing. Survey questions answered during the lockdown period, probing patients’ self-perceived changes retrospectively, revealed that people with chronic pain perceived increases in their pain severity compared to before lockdown. They were also more adversely affected by lockdown compared to pain-free individuals, demonstrating greater increases in anxiety and depressed mood, increased loneliness and reduced levels of physical exercise. Pain catastrophizing was found to be an important factor in predicting the extent of self-perceived increases in pain, and accounted for the relationship between decreased mood and pain. Perceived decreases in levels of physical exercise also independently predicted perceptions of increased pain. Interestingly, actual changes in pain symptoms (measured at two time points at pre- and post-lockdown in a subgroup, N = 85) did not change significantly on average, but those reporting increases also demonstrated greater baseline levels of pain catastrophizing. Overall, the findings suggest that remote pain management provision to target reduction of catastrophizing and increases to physical activity could be beneficial for chronic pain patients in overcoming the adverse effects of lockdown.
Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells
Authors: Duong Angela , Evstratova Alesya , Sivitilli Adam , Hernandez J. Javier , Gosio Jessica , Wahedi Azizia , Sondheimer Neal , Wrana Jeff L. , Beaulieu Jean-Martin , Attisano Liliana , Andreazza Ana C.
Published: June 2020

Mitochondrial health plays a crucial role in human brain development and diseases. However, the evaluation of mitochondrial health in the brain is not incorporated into clinical practice due to ethical and logistical concerns. As a result, the development of targeted mitochondrial therapeutics remains a significant challenge due to the lack of appropriate patient-derived brain tissues. To address these unmet needs, we developed cerebral organoids (COs) from induced pluripotent stem cells (iPSCs) derived from human peripheral blood mononuclear cells (PBMCs) and monitored mitochondrial health from the primary, reprogrammed and differentiated stages. Our results show preserved mitochondrial genetics, function and treatment responses across PBMCs to iPSCs to COs, and measurable neuronal activity in the COs. We expect our approach will serve as a model for more widespread evaluation of mitochondrial health relevant to a wide range of human diseases using readily accessible patient peripheral (PBMCs) and stem-cell derived brain tissue samples.
A mesocosm experiment in ecological physiology: adaptive modulation of energy budget in a hibernating marsupial under chronic caloric restriction
Authors: Nespolo Roberto F. , Fontúrbel Francisco E. , Mejias Carlos , Contreras Rodrigo , Gutierrez Paulina , Ruiz José , Oda Esteban , Sabat Pablo , Hambly Catherine , Speakman John R. , Bozinovic Francisco
Published: June 2020

During the last sixty years, mammalian hibernation (i.e., seasonal torpor) has been interpreted as a physiological adaptation for energy economy. However -and crucially for validating this idea – direct field comparisons of energy expenditure in hibernating and active free-ranging animals are scarce. Using replicated mesocosms and a combination of energy budgeting approaches (i.e., doubly labelled water, rates of CO2production and food intake), we experimentally manipulated energy availability and quantified net energy costs of hibernation in a marsupial. We hypothesized that, when facing chronic caloric restriction (CCR), a hibernator should maximize torpor use for compensating the energetic deficit, compared toad libitumfed individuals (=controls). However, intensifying torpor duration at low temperatures could increase other burdens (e.g., cost of rewarming, freezing risk). In order to explore this trade-off, we followed the complete hibernation cycle of the relict marsupialDromiciops gliroides, and estimated its total energy requirements, and compared this with a control condition. Our results revealed: (1) that energy restricted animals, instead of promoting heat conservation strategies during hibernation (e.g., social clustering and thermoregulation), maximized torpor use and saved just enough energy to cover the deficit, and (2) that hibernation represents a net energy saving of 51% compared with animals that remained active. This work provides compelling evidence of a fine-tuning use of hibernation in response to food availability and presents the first direct estimation of energy savings by hibernation encompassing the total hibernation cycle.
18F-FDG-PET Hyperactivity in Alzheimer’s Disease Cerebellum and Primary Olfactory Cortex
Authors: Meadowcroft Mark D. , Purnell Carson J. , Wang Jian-Li , Karunanayaka Prasanna , Yang Qing X. ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: June 2020

Cerebellar involvement in Alzheimer’s disease (AD) has not been studied to the extent that cortical neuropathological changes have. Historical and recent histopathological literature demonstrate cerebellar AD pathology while functional investigation has demonstrated disrupted intrinsic cortical – cerebellar connectivity in AD. Additionally, olfactory deficits occur early in AD, prior to the onset of clinical symptoms. The neurological basis for the involvement of the cerebellum and olfactory system in the disease course remain unclear.18F-fludeoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed to characterize metabolism in the cerebellum and olfactory region of AD, mild-cognitive impaired (MCI), and age-matched cognitively normal (CN) controls. In contrast to known parietal and temporal lobe FDGhypo-metabolismwithin the default mode network in AD, a significant FDGhyper-metabolismwas found in the cerebellum and olfactory cortical regions (including the piriform cortex, olfactory tubercle, anterior olfactory nucleus, and nucleus accumbens shell). The increase in cerebellum glucose utilization was shown also in late- verses early-MCI patients. The cerebellar and olfactory regions both contain inhibitory distal and inter-neuronal connections that are vulnerable to disruption in AD. The hyper-metabolism in the cerebellum and olfactory structures may reflect disruption of local and system-wide inhibitory networks due to AD neurodegeneration, suggesting a hypothetical mechanism for susceptibility of the olfactory system to early AD pathology.
A scaling approach to estimate the COVID-19 infection fatality ratio from incomplete data
Authors: Seoane Beatriz
Published: June 2020

Abstract

SARS-CoV-2 has disrupted the life of billions of people around the world since the first outbreak was officially declared in China at the beginning of 2020. Yet, important questions such as how deadly it is or its degree of spread within different countries remain unanswered. In this work, we exploit the ‘universal’ growth of the mortality rate with age observed in different countries since the beginning of their respective outbreaks, combined with the results of the antibody prevalence tests in the population of Spain, to unveil both unknowns. We validate these results with an analogous antibody rate survey in the canton of Geneva, Switzerland. We also argue that the official number of deaths over 70 years old is importantly underestimated in most of the countries, and we use the comparison between the official records with the number of deaths mentioning COVID-19 in the death certificates to quantify by how much. Using this information, we estimate the fatality infection ratio (IFR) for the different age segments and the fraction of the population infected in different countries assuming a uniform exposure to the virus in all age segments. We also give estimations for the non-uniform IFR using the sero-epidemiological results of Spain, showing a very similar growth of the fatality ratio with age. Only for Spain, we estimate the probability (if infected) of being identified as a case, being hospitalized or admitted in the intensive care units as function of age. In general, we observe a nearly exponential growth of the fatality ratio with age, which anticipates large differences in total IFR in countries with different demographic distributions, with numbers that range from 1.82% in Italy, to 0.62% in China or even 0.14% in middle Africa.
Effect of temperature on life-history traits and mating calls of a field cricket,Acanthogryllus asiaticus
Authors: Singh Richa , Prathibha P , Jain Manjari
Published: June 2020

Ectotherms are sensitive to the changes in ambient temperature with respect to their physiology and development. To compensate for the effects of variation in temperature, ectotherms exhibit physiological plasticity which can be for short or long term. An extensive body of literature exists towards understanding these effects and the solutions ectotherms have evolved. However, to what extent rearing temperature during early life stages impacts the behaviour expressed in adulthood is less clearly understood. In the present study, we aimed to examine the effect of developmental temperature on life-history traits and mating call features in a tropical field cricket,Acanthogryllus asiaticus. We raisedA. asiaticusat two different developmental conditions: 25°C and 30°C. We found developmental time and adult lifespan of individuals reared at 30°C to be shorter than those at 25°C. Increased developmental temperature influenced various body size parameters differentially. Males raised at 30°C were found to be larger and heavier than those raised at 25°C, makingA. asiaticusan exception to the temperature-size rule. We found a significant effect of the change in immediate ambient temperature on different call features of both field-caught and lab-bred individuals. In addition, developmental temperature also affected mating call features as individuals raised at higher temperature produced faster calls with a higher peak frequency compared to those raised at lower temperature. However, the interaction of both developmental and immediate temperature on mating calls showed differential effects. Our study highlights the importance of understanding how environmental temperature shapes life-history and sexual communication in crickets.
A sensory cell diversifies its output by varying Ca2+influx-release coupling among presynaptic active zones for wide range intensity coding
Authors: Özçete Özge Demet , Moser Tobias
Published: June 2020

The cochlea encodes sound intensities ranging over six orders of magnitude which is collectively achieved by functionally diverse spiral ganglion neurons (SGNs). However, the mechanisms enabling the SGNs to cover specific fractions of the audible intensity range remain elusive. Here we tested the hypothesis that intensity information, fully contained in the receptor potential of the presynaptic inner hair cell (IHC), is fractionated via heterogeneous synapses. We studied the transfer function of individual active zones (AZs) using dual-color Rhod-FF and iGluSnFR imaging of Ca2+and glutamate release. AZs differed in the voltage dependence of release: AZs residing at the IHCs’ pillar (abneural) side activate at more hyperpolarized potentials and typically showed tight control of release by few Ca2+-channels. We conclude that heterogeneity of voltage dependence and release-site coupling of Ca2+-channels among the AZs varies synaptic transfer within individual IHCs and, thereby, likely contributes to the functional diversity of SGNs.
A Flexible Statistical Framework for Estimating Excess Mortality
Authors: Acosta Rolando J. , Irizarry Rafael A.
Published: June 2020

Quantifying the impact of natural disasters or epidemics is critical for guiding policy decisions and interventions. When the effects of an event are long-lasting and difficult to detect in the short term, the accumulated effects can be devastating. Mortality is one of the most reliably measured health outcomes, partly due to its unambiguous definition. As a result, excess mortality estimates are an increasingly effective approach for quantifying the effect of an event. However, the fact that indirect effects are often characterized by small, but enduring, increases in mortality rates present a statistical challenge. This is compounded by sources of variability introduced by demographic changes, secular trends, seasonal and day of the week effects, and natural variation. Here we present a model that accounts for these sources of variability and characterizes concerning increases in mortality rates with smooth functions of time that provide statistical power. The model permits discontinuities in the smooth functions to model sudden increases due to direct effects. We implement a flexible estimation approach that permits both surveillance of concerning increases in mortality rates and careful characterization of the effect of a past event. We demonstrate our tools’ utility by estimating excess mortality after hurricanes in the United States and Puerto Rico. We use Hurricane Maria as a case study to show appealing properties that are unique to our method compared to current approaches. Finally, we show the flexibility of our approach by detecting and quantifying the 2014 Chikungunya outbreak in Puerto Rico and the COVID-19 pandemic in the United States. We make our tools available through the excessmort R package available from https://cran.r-project.org/web/packages/excessmort/.
Knowledge and Awareness-based Survey of COVID-19 within the Eye Care Profession in Nepal: Misinformation is Hiding the Truth
Authors: Das Sandip Sanyam , Kumar Sanjay Sah , Chaudhary Pankaj , Hoffman Jeremy J
Published: June 2020

Background

Nepal is currently under lockdown due to the COVID-19 pandemic with misinformation circulating on social media. This study aimed to analyse the knowledge and awareness of COVID-19 amongst eye care professionals in Nepal.

Methodology

We invited 600 participants from 12 ophthalmic centres across Nepal to complete a qualitative, anonymous online survey.

Results

Of the 600 eye care professionals invited, 310 (51%) participated in the survey. The symptoms of COVID-19 were known to 94%, whilst only 49% were aware of disease transmission. 98% of participants recognised the World Health Organization’s (WHO) awareness message, yet 41% of participants felt that consumption of hot drinks helps to destroy the virus. 41% disagreed that PPE should be mandatory for eye care practitioners.

Conclusion

There is still considerable scope to improve the knowledge of COVID-19 amongst ophthalmic professionals in Nepal. Opinion is also split on measures to prevent transmission, with misinformation potentially fuelling confusion.
Studying the effect of lockdown using epidemiological modelling of COVID-19 and a quantum computational approach using the Ising spin interaction
Authors: Padhi Anshuman , Pradhan Sudev , Sahu Pragna Paramita , Kalyani S , Behera Bikash K. , Panigrahi Prasanta K.
Published: June 2020

COVID-19 is a respiratory tract infection that can range from being mild to fatal. In India, the countrywide lockdown has been imposed since 24th march, 2020, and has got multiple extensions with different guidelines for each phase. Among various models of epidemiology, we use the SIR(D) model to analyze the extent to which this multi-phased lockdown has been active in ‘flattening the curve’ and lower the threat. Analyzing the effect of lockdown on the infection may give us a better insight into the evolution of epidemic while implementing the quarantine procedures as well as improving the healthcare facilities. For accurate modelling, incorporating various parameters along with sophisticated computational facilities, are required. Parallel to SIRD modelling, we tend to compare it with the Ising model and derive a quantum circuit that incorporates the rate of infection and rate of recovery, etc as its parameters. The probabilistic plots obtained from the circuit qualitatively resemble the shape of the curve for the spread of Coronavirus. We also demonstrate how the curve flattens when the lockdown is imposed. This kind of quantum computational approach can be useful in reducing space and time complexities of a huge amount of information related to the epidemic.
Dynamics of the SARS-CoV-2 epidemic in the earliest-affected areas in Italy: Mass screening for SARS-CoV-2 serological positivity (SARS-2-SCREEN)
Authors: Pagani Gabriele , Bernacchia Dario , Conti Federico , Giacomelli Andrea , Rondanin Rossana , Scolari Vittore , Boracchi Patrizia , Gandolfi Cecilia Eugenia , Castaldi Silvana , Biganzoli Elia , Galli Massimo
Published: June 2020

Background

Several municipalities in the Lombardy Region have been affected by the SARS-CoV-2 infection since the earliest stages of the epidemic. To date, 89442 confirmed cases have been diagnosed in Lombardy, and mortality in several municipalities has already surpassed that of the past decade. Currently, the true extent of the SARS-CoV-2 infection remains unknown as several affected subjects may have been asymptomatic or have presented mild disease, thus not resulting in the identified COVID-19 cases.

Methods

This cross-sectional study aims to define the spread of infection within the population by determining the seroprevalence of IgG antibodies directed against SARS-CoV-2 by rapid immunochromatographic testing and subsequent confirmation by serology on venous blood by liquid phase immunochemical testing, also allowing to compare the two methods. Testing will be performed on adults and minors residing, domiciled or working in several municipalities of the Lombardy Region, involved in the initial stages of the epidemic. The study will include rapid finger-prick testing and venous sampling for antibodies against SARS-CoV-2, and nasopharyngeal swabbing (NPS). Concurrent notification of test results will occur via the regional healthcare information system (SISS).

Discussion

This study was developed with the desire to understand the seroprevalence of SARS-CoV-2 infection and the epidemiological transmission characteristics of this virus. Understanding the spread and severity of the disease could help in the implementation of effective infection surveillance containment and countermeasures facilitating the identification of cases that have been exposed to the virus and the traceability of contacts.

This study has been approved by the Ethics Committee of the University of Milan (35/2020).
Clinical evaluation of self-collected saliva by RT-qPCR, direct RT-qPCR, RT-LAMP, and a rapid antigen test to diagnose COVID-19
Authors: Ikeda Mayu , Imai Kazuo , Tabata Sakiko , Miyoshi Kazuyasu , Murahara Nami , Mizuno Tsukasa , Horiuchi Midori , Kato Kento , Imoto Yoshitaka , Iwata Maki , Mimura Satoshi , Ito Toshimitsu , Tamura Kaku , Kato Yasuyuki
Published: June 2020

Background

The clinical performance of six molecular diagnostic tests and a rapid antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were clinically evaluated for the diagnosis of coronavirus disease 2019 (COVID-19) in self-collected saliva.

Methods

Saliva samples from 103 patients with laboratory-confirmed COVID-19 (15 asymptomatic and 88 symptomatic) were collected on the day of hospital admission. SARS-CoV-2 RNA in saliva was detected using a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) laboratory-developed tes (LDT), a cobas SARS-CoV-2 high-throughput system, three direct RT-qPCR kits, and reverse-transcription loop mediated isothermal amplification (RT-LAMP). Viral antigen was detected by a rapid antigen immunochromatographic assay.

Results

Of the 103 samples, viral RNA was detected in 50.5–81.6% of the specimens by molecular diagnostic tests and an antigen was detected in 11.7% of the specimens by the rapid antigen test. Viral RNA was detected at a significantly higher percentage (65.6–93.4%) in specimens collected within 9 d of symptom onset compared to that of specimens collected after at least 10 d of symptom onset (22.2–66.7%) and that of asymptomatic patients (40.0–66.7%). Viral RNA was more frequently detected in saliva from males than females.

Conclusions

Self-collected saliva is an alternative specimen diagnosing COVID-19. LDT RT-qPCR, cobas SARS-CoV-2 high-throughput system, direct RT-qPCR except for one commercial kit, and RT-LAMP showed sufficient sensitivity in clinical use to be selectively used according to clinical settings and facilities. The rapid antigen test alone is not recommended for initial COVID-19 diagnosis because of its low sensitivity.

Key points

Six molecular diagnostic tests showed equivalent and sufficient sensitivity in clinical use in diagnosing COVID-19 in self-collected saliva samples. However, a rapid SARS-CoV-2 antigen test alone is not recommended for use without further study.
Bacteriological Quality of Beef and Hygiene Practices of Food Handlers in Butcheries in Kasama District, Zambia
Authors: Hanyinza Sara , Ndashe Kunda , Mfune Ruth , Chirwa Emmanuel , Mwanza Grace , Phiri Bruno , Mumba Bernadette , Mubanga Maron , Hang’ombe Bernard
Published: June 2020

The most common health risk associated with consumption of beef is microbial contamination, therefore the study was aimed to assess the level of bacterial contamination of beef and evaluate the hygienic practices in butcheries in Kasama district. Beef samples were collected from participating butcheries and a structured questionnaire was also administered to the food handlers.

Microbiological quality of the beef samples was determined by Aerobic Plate Count (APC), Faecal Coliform Count (FCC) and bacterial isolation such as Salmonella spp and Staphylococcus aureus. The APC results revealed 40.7% of the butcheries sold meat in good bacterial condition (<4 Log10 cfu/g) while 40.7% and 18.5% were critical (4-5 Log10 cfu/g) and non-acceptable conditions (>5 Log10 cfu/g), respectively. The FCC revealed that 74.1% of the butcheries sold meat in good bacterial conditions (<2 Log10 cfu/g), while 14.8% and 11.1% were critical (2-3 Log10 cfu/g) and non-acceptable conditions (>3 Log10 cfu/g), respectively. Staphylococcus aureus was isolated from 37% of the butcheries, none of the outlets recorded Salmonella spp.

Overall, the microbial quality of most (74.1%) of the market ready beef in Kasama district was acceptable for human consumption. Therefore, regular bacteriological monitoring and maintaining hygiene in the sales outlets and distribution chain is mandatory.
Closed form solution of the SIR model for the COVID-19 outbreak in Italy
Authors: Giubilei Riccardo
Published: June 2020

The CODIV-19 outbreak in early 2020 generated a tremendous effort of epidemiologists and researchers to fit the experimental data with the solutions of the SIR model equations [1] or with more sophisticated models. In this paper we show that under same hypotheses, a closed form solution exists that reasonably fits the experimental data for Italy, and the results can be extended to any other area.
Molecular mechanism of SARS-CoV-2 components caused ARDS in murine model
Authors: Gu Tingxuan , Zhao Simin , Jin Guoguo , Song Mengqiu , Zhi Yafei , Zhao Ran , Ma Fayang , Zheng Yaqiu , Wang Keke , Liu Hui , Xin Mingxia , Han Wei , Li Xiang , Dong Christopher D , Liu Kangdong , Dong Zigang
Published: June 2020

COVID-19 has become a major challenge to global health, and until now, no efficient antiviral agents have been developed. The SARS-CoV-2 infection is characterized by pulmonary and systemic inflammation in severe patients, and acute respiratory distress syndrome (ARDS) caused respiratory failure contributes to most mortalities. There is an urgent need for developing effective drugs and vaccines against SARS-CoV-2 and COVID-19 caused ARDS. However, most researchers cannot perform SARS-CoV-2 related researches due to lacking P3 or P4 facility. We developed a non-infectious, highly safety, time-saving SARS-CoV-2 components induced murine model to study the SARS-CoV-2 caused ARDS and cytokine storm syndrome (CSS). We also investigated mAbs and inhibitors which potentially neutralize the pro-inflammatory phenotype of COVID-19, and found that anti-IL-1α, anti-IL-6, anti-TNFα, anti-GM-CSF mAbs, p38 inhibitor, and JAK inhibitor partially relieved CSS. Besides, anti-IL-6, anti-TNFα, anti-GM-CSF mAbs and inhibitors of p38, ERK, and MPO somewhat reduced neutrophilic alveolitis in the lung. In all, we established the murine model mimic of COVID-19, opening a biosafety and less time-consuming avenue for clarifying the mechanism of ARDS and CSS in COVID-19 and developing the therapeutic drugs.
Ozone nanobubble treatment effectively reduced pathogenic Gram positive and negative bacteria in freshwater and safe for tilapia
Authors: Jhunkeaw Chayuda , Khongcharoen Nareerat , Rungrueng Naruporn , Sangpo Pattiya , Panphut Wattana , Thapinta Anat , Senapin Saengchan , St-Hilaire Sophie , Dong Ha Thanh
Published: June 2020

High concentrations of pathogenic bacteria in water usually results in outbreaks of bacterial diseases in farmed fish. Here, we explored the potential application of an emerging nanobubble technology in freshwater aquaculture. Specifically, we aimed to determine if this technology was effective at reducing the concentration of pathogenic bacteria in the water, and to assess whether it was safe for fish. An ozone nanobubble (NB-O3) treatment protocol was established based on examination of nanobubble size, concentration, disinfection property, and impact on fish health. A 10-min treatment with NB-O3in 50 L water generated approximately 2-3 × 107bubbles with majority sizes less than 130 nm and ozone level of ∼800 mV ORP. A single treatment with water contaminated with eitherStreptococcus agalactiaeorAeromonas veroniieffectively reduced 96.11-97.92 % of the bacterial load. This same protocol was repeated 3 times with 99.93-99.99 % reduction in the bacterial concentration. In comparison, bacterial concentration the control tanks remained the same level during the experiments. In fish-cultured water with the presence of organic matter (e.g. mucus, feces, bacterial flora, feed, etc.), the disinfection property of NB-O3was reduced i.e bacterial concentration was reduced by 42.94 %, 84.94 % and 99.27 % after the first, second and third treatments, respectively. To evaluate the safety of NB-O3to fish, juvenile Nile tilapia were exposed to NB-O3treatment for 10 minutes. No mortality was observed during the treatment or 48 h post treatment. Gill histology examination revealed that a single NB-O3treatment caused no alteration morphology. However, damage in the gill filaments was noticed in the fish receiving two or three consecutive exposures within the same day. Results of all the experiments conducted in this study suggest that NB-O3technology is promising for controlling pathogenic bacteria in aquaculture systems, and may be useful at reducing the risk of bacterial disease outbreaks in farmed fish.
Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism
Authors: Parvez Md Sorwer Alam , Rahman Mohammad Mahfujur , Morshed Md Niaz , Rahman Dolilur , Anwar Saeed , Hosen Mohammad Jakir
Published: June 2020

As the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rages across the world, killing hundreds of thousands and infecting millions, researchers are racing against time to elucidate the viral genome. Some Bangladeshi institutes are also in this race, sequenced a few isolates of the virus collected from Bangladesh. Here, we present a genomic analysis of 14 isolates. The analysis revealed that SARS-CoV-2 isolates sequenced from Dhaka and Chittagong were the lineage of Europe and the Middle East, respectively. Our analysis identified a total of 42 mutations, including three large deletions, half of which were synonymous. Most of the missense mutations in Bangladeshi isolates found to have weak effects on the pathogenesis. Some mutations may lead the virus to be less pathogenic than the other countries. Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh.
Modelling the effects of PPARβδ of innate inflammatory responses in lung tissues
Authors: Diaz Noelia Perez , Lione Lisa A , Hutter Victoria , Mackenzie Louise S.
Published: June 2020

Peroxisome proliferator activated receptor beta/delta (PPARβ/δ) is a nuclear receptor ubiquitously expressed in cells whose signaling controls inflammation and metabolism. However, there are great discrepancies in understanding the role of PPARβ/δ, having both anti- and pro-effects on inflammation. Understanding the PPARβ/δ mechanism of action may provide new molecular mechanisms for treating a variety of inflammatory-related diseases.

We studied the PPARβ/δ-regulation of LPS-induced inflammation of pulmonary artery, bronchi and parenchyma from rat, using different combinations of agonists (GW0742 or L-165402) and antagonists (GSK3787 or GSK0660). LPS-induced inflammation is largely regulated by PPARβ/δ in the pulmonary artery, but it is a minor factor in bronchi or parenchyma. Agonists do not significantly inhibit inflammation, but activates the PPARβ/δ induction mode of action. Surprisingly, co-incubation of the tissue with agonist plus antagonist shows anti-inflammatory effects and switches the PPARβ/δ mode of action from induction to trans-repression, indicating that the PPARβ/δ induction mode of action is pro-inflammatory and the trans-repression anti-inflammatory. Us of Computational chemistry methods indicates that PPARβ/δ agonists are predicted to form polar interactions with the residues His287, His413 and Tyr437 whilst PPARβ/δ antagonists form polar interactions with the residues Thr252 and Asn307. Further, our modelling indicates favorable binding energies and the feasibility of simultaneous binding of two ligands in the PPARβ/δ binding pocket. In summary, this study provides novel insight into the complex relationship between ligand binding profiles and functional outcomes in a rat lung inflammation model, which will help inform the design of novel therapies for inflammatory lung diseases.
EXOC1 regulates cell morphology of spermatogonia and spermatocytes in mice
Authors: Osawa Yuki , Usui Miho , Kuba Yumeno , Le Hoai Thu , Mikami Natsuki , Nakagawa Toshinori , Daitoku Yoko , Kato Kanako , Shawki Hossam Hassan , Ikeda Yoshihisa , Kuno Akihiro , Morimoto Kento , Tanimoto Yoko , Huong Dinh Tra Thi , Murata Kazuya , Yagami Ken-ichi , Ema Masatsugu , Yoshida Shosei , Takahashi Satoru , Mizuno Seiya , Sugiyama Fumihiro
Published: June 2020

Spermatogenesis requires high regulation of germ cell morphology. The spermatogonia regulates its differentiation state by its own migration. The male germ cells differentiate and mature with the formation of syncytia, failure of forming the appropriate syncytia results in the arrest of spermatogenesis at the spermatocyte stage. However, the detailed molecular mechanisms of male germ cell morphological regulation are unknown. Here, we found that EXOC1 is important for the pseudopod formation of spermatogonia and spermatocyte syncytia in mice. We found that while EXOC1 contributes to the inactivation of Rac1 in the pseudopod formation of spermatogonia, in spermatocyte syncytium formation, EXOC1 and SNAP23 cooperate with STX2. Our results showed that EXOC1 functions in concert with various cell morphology regulators in spermatogenesis. Since EXOC1 is known to bind to several cell morphogenesis factors, this study is expected to be the starting point for the discovery of many morphological regulators of male germ cells.
Boundary sequences flanking the mouse tyrosinase locus ensure faithful pattern of gene expression
Authors: Seruggia Davide , Fernández Almudena , Cantero Marta , Fernández-Miñán Ana , Gomez-Skarmeta José Luis , Pelczar Pawel , Montoliu Lluis
Published: June 2020

Control of gene expression is dictated by cell-type specific regulatory sequences that physically organize the structure of chromatin, including promoters, enhancers and insulators. While promoters and enhancers convey cell-type specific activating signals, insulators prevent the cross-talk of regulatory elements within adjacent loci and safeguard the specificity of action of promoters and enhancers towards their targets in a tissue specific manner. Using the mouse tyrosinase (Tyr) locus as an experimental model, a gene whose mutations are associated with albinism, we described the chromatin structure in cells at two distinct transcriptional states. Guided by chromatin structure, through the use of Chromosome Conformation Capture (3C), we identified sequences at the 5’ and 3’ boundaries of this mammalian gene that function as enhancers and insulators. By CRISPR/Cas9-mediated chromosomal deletion, we dissected the functions of these two regulatory elements in vivo in the mouse, at the endogenous chromosomal context, and proved their role as genomic insulators, shielding theTyrlocus from the expression patterns of adjacent genes.
The process evaluation of a school-based physical activity intervention: influencing factors and potential consequences of implementation
Authors: Åvitsland Andreas , Ohna Stein Erik , Dyrstad Sindre Mikal , Tjomsland Hege Eikeland , Lerum Øystein , Leibinger Eva
Published: June 2020

Purpose

This paper evaluates the implementation of a school-based physical activity intervention and discusses how the intervention outcomes can be influenced by the implementation.

Design/methodology/approach

In four of the nine lower secondary schools in which the intervention was conducted, the authors examined implementation fidelity, adaptation, quality, responsiveness and dose received. The authors conducted focus group interviews with teachers (n = 8) and students (n = 46) and made observations. Dose delivered was examined quantitatively, with weekly registrations.

Findings

Results showed that two out of four schools made few and positive adaptations, implemented the intervention with high fidelity and quality and responded positively. Four main factors were found to influence implementation: frame factors, intervention characteristics, participant characteristics and provider characteristics.

Research limitations/implications

A cross-sectional design was used and may not represent implementation throughout the whole school year.

Practical implications

In terms of large-scale implementation, the intervention may be generalizable. However, intervention criteria such as adequate facilities and a flexible timetable may be unattainable for some schools. The intervention can be adapted without compromising its purpose, but adaptations should be a result of cooperation between students and teachers.

Originality/value

Process evaluations on this topic are rare. This study adds to a limited knowledge base concerning what factors may influence implementation of school-based physical activity interventions for adolescents.
Experiential learning for Chinese companies to complete cross-border acquisitions: the case of Chinese acquirers
Authors: Wang Le , Schweizer Lars , Michaelis Björn
Published: June 2020

Purpose

In a contribution to the emerging research examining Chinese cross-border acquisitions (CBAs), the authors observe experiential learning applications for enhancing M&A completions. By emphasizing knowledge transfer, the authors reveal how target-to-target industry similarity and bidder-to-target cultural distance affect learning outcomes.

Design/methodology/approach

Using a binary logistic regression model, the authors examine a sample of CBA attempts announced by Chinese companies from January 2002 to December 2012 to identify the variables that affect the completion of CBAs.

Findings

The authors find that foreign acquisition experience but not domestic acquisition experience enhances subsequent acquisition attempts, especially when prior and focal target companies share the dominant industrial logic. Learning transfer is negatively affected when target countries are more culturally distant from China, but learning benefits appear to increase under strong bidder-to-target cultural distance.

Originality/value

By investigating learning in the precompletion stage in Chinese outward CBAs, the authors complement research that uses postacquisition performance to assess learning. The authors’ more fine-grained characterization reveals that acquisition experience increases knowledge transfer through experiential learning. Furthermore, the authors show that dominant industrial logic and cultural distance are underexplored contextual conditions, although they interact with foreign and domestic experience to affect the completion of CBAs.
Public, private or hybrid? Providing care services under austerity: the case of Italy
Authors: Dorigatti Lisa , Mori Anna , Neri Stefano
Published: June 2020

Purpose

The paper examines the different trajectories of externalisation and the development of different kinds of welfare mix in three different sub-sectors of socio-educational services: long-term care for the elderly, early childhood services and kindergartens. By integrating the industrial relations and comparative public administration literatures, it analyses the different rationales underpinning contracting-out decisions of Italian local governments.

Design/methodology/approach

The paper adopts a multi-method, multi-level approach: quantitative data on the provision of socio-educational services and the nature of the providers are combined with the analysis of 12 case studies of municipalities through 80 semi-structured interviews and documentary analysis.

Findings

The paper argues that differentials in labour regulation across the public/private divide and the consequent possibility to access labour markets characterised by cheaper labour and higher organisational flexibility are a key explanation in local governments' decisions to outsource. Despite labour market factors playing a prominent role, their relevance is significantly tempered by political and social factors and particularly by the strong opposition of citizens, personnel and trade unions to pure market solutions in the provision of such services. However, the centrality of these factors depends on the nature of the services: political sensibility against privatisation proved to be stronger in kindergartens, while services for the elderly were more frequently and less contentiously privatised.

Originality/value

The main contribution is the integration of the two research traditions to analyse patterns of outsourcing in the socio-educational services in Italy, showing that neither of them is able, alone, to explain the different private/public mix characterising different social and educational services.
What entrepreneurs do? Entrepreneurial action guided by entrepreneurial opportunities and entrepreneurial learning in early internationalising firms
Authors: Masango Shingairai Grace , Lassalle Paul
Published: June 2020

Purpose

There is a growing interest in exploring the interface between international marketing and entrepreneurial opportunities. This paper contributes by defining and elucidating entrepreneurial action in early internationalising software firms and the corresponding emergent international marketing activities. Entrepreneurial action in early internationalising software firms is explored through the operationalisation of a reconceptualised entrepreneurial opportunity construct and the associated entrepreneurial learning processes.

Design/methodology/approach

The paper adopts an inductive approach, which traces the evolution of five early internationalising propriety software South African firms; from the new venture idea to the establishment of the international entrepreneurial opportunity.

Findings

The findings provide support for entrepreneurial action guided by: prior industry experience, entrepreneurial alertness, opportunity confidence and two levels of entrepreneurial learning; experiential and double-loop learning. Learning by doing allows for the continuous evaluation of the new venture idea leading to the international entrepreneurial opportunity. Market responsiveness and continuous product development resulting in the emergence of the firm's inward international marketing activities constitute the key outcomes of entrepreneurial action.

Research limitations/implications

The study is limited to a specific technology context, which is young software firms whose inward directed internationalisation activities coalesce around the development of their proprietary software technology.

Originality/value

Based on an original dataset of early internationalising software firms from South Africa, this paper inductively operationalises and conceptualises entrepreneurial action as the combined interaction of four key constructs: contingent effects, attitudes to opportunities, learning by doing and entrepreneurial activities leading to the firm's inward international marketing activities and a diversified international client and end-user base.