bluuebunny/crossref_metadata_2025 huggingface dataset:
Taxonomy of Micronesian monitors (Reptilia: Squamata:
Varanus
): endemic status of new species argues for caution in pursuing eradication plans
Authors: Weijola Valter , Vahtera Varpu , Koch André , Schmitz Andreas , Kraus Fred
Published: May 2020

In the light of recent phylogenetic studies, we re-assess the taxonomy and biogeography of the
Varanus
populations distributed in the Micronesian islands of Palau, the Western Carolines and the Marianas. Whether these populations are of natural origin or human introductions has long been contentious, but no study has fully resolved that question. Here, we present molecular and morphological evidence that monitor lizards of the
Varanus indicus
Group reached both Palau and the Mariana Islands sometime in the late Pleistocene and subsequently differentiated into two separate species endemic to each geographical region. One species is confined to the Mariana Islands, and for these populations, we revalidate the name
V. tsukamotoi
Kishida, 1929. The other species has a disjunct distribution in Palau, the Western Carolines and Sarigan Island in the Northern Marianas and is herein described as
V. bennetti
sp. nov. Both species are most closely allied to each other,
V. lirungensis
and
V. rainerguentheri
, suggesting that colonization of Micronesia took place from the Moluccas. We discuss the biogeographic distributions of both species in the light of the likely colonization mechanism and previous arguments for human introduction, and we argue that bounties for Palauan populations are ill-advised and plans for eradication of some other populations must first demonstrate that they are, in fact, introduced and not native.
MIGRANTS IN TRANSIT AND ASYLUM SEEKERS IN MEXICO: AN EPIDEMIOLOGICAL ANALYSIS OF THE COVID-19 PANDEMIC
Authors: Bojorquez Ietza , Infante César , Vieitez Isabel , Larrea Silvana , Santoro Chiara
Published: May 2020

BACKGROUND

Migrants could be disproportionately affected by the COVID-19 pandemic, yet little is known so far of the epidemiology of the disease among them, especially in low- and middle-income countries.

OBJECTIVE

To describe the epidemiology of suspect cases of COVID-19 in migrants in transit and asylum seekers in Mexico, and to compare their characteristics with those of non-migrants.

METHODS

This was a secondary analysis of information from the surveillance system of Mexico from January 1 to May 3 2020, identifying persons from the main sending countries of mixed migrant flows in Mexico (Central America, the Caribbean, Venezuela and African countries), in northern and southern Mexican border states. We compared the demographic and clinical characteristics, risk conditions, and epidemic curves for migrants and non-migrants. Also, we estimated the cumulative incidence for non-migrants, and for migrants in two scenarios defined by different estimations of their population size.

RESULTS

Migrants were on average younger, had less accompanying risk conditions, and a lower percentage of suspect cases tested positive for COVID-19. The odds of hospitalization were lower among migrants, but the difference disappeared after adjusting by age, gender and underlying risk conditions. The cumulative incidence ratios comparing migrants with non-migrants were 6.12 (CI95% 4.75,7.77) for the first scenario, and 1.49 (CI95% 1.15,1.89) for the second scenario.

CONCLUSION

Migrants and asylum seekers in Mexico are at increased risk for infectious respiratory diseases, and could be disproportionately affected by COVID-19. It is important to continue monitoring the situation, with more detailed information about migration status, living conditions and other determinants of migrants health.
On the Front (Phone) Lines: Results of a COVID-19 Hotline in Northeast Ohio
Authors: Margolius David , Hennekes Mary , Yaho Jimmy , Einstadter Douglas , Gunzler Douglas , Chehade Nabil , Sehgal Ashwini R , Tarabichi Yasir , Perzynski Adam T
Published: May 2020

ABSTRACT

Importance: Severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease of 2019 (COVID-19) have presented immense challenges for health care systems. Many regions have struggled to adapt to disruptions to health care practice and employ systems that effectively manage the demand for services.

Objective: To examine the effectiveness of the first five weeks of a 24/7 physician-staffed COVID-19 hotline.

Design: Cohort study using electronic health records.

Setting: A single large health care system in Northeast Ohio.

Participants: During 5 weeks of operation, 10,112 patients called the hotline (callers) and were evaluated by a registered nurse (RN) using standardized protocols. Of these, 4,213 (42%) were referred for a physician telehealth visit (telehealth patients). The mean age of callers was 42 years. 67% were female, 51% white, and 46% were on Medicaid or uninsured.

Intervention: Physician telehealth visits for COVID-19.

Main Outcomes and Measures: We describe clinical diagnosis, patient characteristics (age, sex race/ethnicity, smoking status, insurance status), and visit disposition. We use logistic regression to evaluate associations between patient characteristics, visit disposition and subsequent emergency department use, hospitalization, and SARS-Cov-2 PCR testing.

Results: Common caller concerns included cough, fever, and shortness of breath. Most telehealth patients (79%) were advised to self-isolate at home, 14% were determined to be unlikely to have COVID-19, 3% were advised to seek emergency care, and 4% had miscellaneous other dispositions. A total of 287 (7%) patients had a subsequent ED visit, and 44 (1%) were hospitalized with a COVID-19 diagnosis. Of the callers, 482 (5%) had a COVID-19 test reported with 69 (14%) testing positive. Among patients advised to stay at home, 83% had no further face-to-face visits. In multivariable results, only a physician recommendation to seek emergency care was associated with emergency room use (OR=4.73, 95%CI 1.37-16.39, p=.014). Only older age was associated with having a positive test result.

Conclusions and Relevance: Robust, physician-directed telehealth services can meet a wide range of needs during the acute phase of a pandemic, conserving scarce resources such as personal protective equipment and testing supplies and preventing the spread of infections to patients and health care workers.
Demonstration of a Longitudinal Action Medical Mission (LAMM) Model to Teach Point-of-Care Ultrasound in Resource-Limited Settings
Authors: Yao Michael , Uhr Lauren , Daghlian George , Amrute Junedh M. , Deshpande Ramya , Mathews Benji , Patel Sanjay A. , Henri Ricardo , Liu Gigi , Reierson Kreegan , Johnson Gordon
Published: May 2020

BACKGROUND

Short-term medical missions prevail as the most common form of international medical volunteerism, but they are ill-suited for medical education and training local providers in resource-limited settings.

OBJECTIVE

The purpose of this study is to evaluate the effectiveness of a longitudinal educational program in training clinicians how to perform point-of-care ultrasound (POCUS) in resource-limited clinics.

DESIGN

A retrospective study of such a four-month POCUS training program was conducted with clinicians from a rural hospital in Haiti. The model included one-on-one, in-person POCUS teaching sessions by volunteer instructors from the United States and Europe. The Haitian trainees were assessed at the start of the program and at its conclusion by a direct objective structured clinical examination (OSCE), administered by the visiting instructors, with similar pre- and post-program ultrasound competency assessments.

RESULTS

Post-intervention, a significant improvement was observed (p < 0.0001), and each trainee showed significant overall improvement in POCUS competency independent of the initial competency pre-training (p < 0.005). There was a statistically significant improvement in POCUS application for five of the six medically relevant assessment categories tested.

CONCLUSION

Our results provide a proof-of-concept for the longitudinal education-centered healthcare delivery framework in a resource-limited setting. Our longitudinal model provides local healthcare providers the skills to detect and diagnose significant pathologies, thereby reducing avoidable morbidity and mortality at little or no addition cost or risk to the patient. Furthermore, training local physicians obviates the need for frequent volunteering trips, saving costs in healthcare training and delivery.
Forecasting Transmission Dynamics of COVID-19 Epidemic in India Under Various Containment Measures- A Time-Dependent State-Space SIR Approach
Authors: Deo Vishal , Chetiya Anuradha R. , Deka Barnali , Grover Gurprit
Published: May 2020

Objectives

Our primary objective is to predict the dynamics of COVID-19 epidemic in India while adjusting for the effects of various progressively implemented containment measures. Apart from forecasting the major turning points and parameters associated with the epidemic, we intend to provide an epidemiological assessment of the impact of these containment measures in India.

Methods

We propose a method based on time-series SIR model to estimate time-dependent modifiers for transmission rate of the infection. These modifiers are used in state-space SIR model to estimate reproduction numberR0, expected total incidence, and to forecast the daily prevalence till the end of the epidemic. We consider four different scenarios, two based on current developments and two based on hypothetical situations for the purpose of comparison.

Results

Assuming gradual relaxation in lockdown post 17 May 2020, we expect the prevalence of infecteds to cross 9 million, with at least 1 million severe cases, around the end of October 2020. For the same case, estimates ofR0for the phases no-intervention, partial-lockdown and lockdown are 4.46 (7.1), 1.47 (2.33), and 0.817 (1.29) respectively, assuming 14-day (24-day) infectious period.

Conclusions

Estimated modifiers give consistent estimates of unadjustedR0across different scenarios, demonstrating precision. Results corroborate the effectiveness of lockdown measures in substantially reducingR0. Also, predictions are highly sensitive towards estimate of infectious period.
Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence
Authors: Meltzer David O. , Best Thomas J. , Zhang Hui , Vokes Tamara , Arora Vineet , Solway Julian
Published: May 2020

Importance

Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment.

Objective

To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19.

Design

Retrospective cohort study

Setting

University of Chicago Medicine

Participants

Patients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient (last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased).

Main Outcomes and Measures

The main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed.

Results

Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age≥50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%]) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group. Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19.

Conclusions and Relevance

Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.
Defining the Pandemic at the State Level: Sequence-Based Epidemiology of the SARS-CoV-2 virus by the Arizona COVID-19 Genomics Union (ACGU)
Authors: Ladner Jason T. , Larsen Brendan B. , Bowers Jolene R. , Hepp Crystal M. , Bolyen Evan , Folkerts Megan , Sheridan Krystal , Pfeiffer Ashlyn , Yaglom Hayley , Lemmer Darrin , Sahl Jason W. , Kaelin Emily A. , Maqsood Rabia , Bokulich Nicholas A. , Quirk Grace , Watts Thomas D. , Komatsu Kenneth , Waddell Victor , Lim Efrem S. , Caporaso J. Gregory , Engelthaler David M. , Worobey Michael , Keim Paul
Published: May 2020

In December of 2019, a novel coronavirus, SARS-CoV-2, emerged in the city of Wuhan, China causing severe morbidity and mortality. Since then, the virus has swept across the globe causing millions of confirmed infections and hundreds of thousands of deaths. To better understand the nature of the pandemic and the introduction and spread of the virus in Arizona, we sequenced viral genomes from clinical samples tested at the TGen North Clinical Laboratory, provided to us by the Arizona Department of Health Services, and at Arizona State University and the University of Arizona, collected as part of community surveillance projects. Phylogenetic analysis of 79 genomes we generated from across Arizona revealed a minimum of 9 distinct introductions throughout February and March. We show that >80% of our sequences descend from clades that were initially circulating widely in Europe but have since dominated the outbreak in the United States. In addition, we show that the first reported case of community transmission in Arizona descended from the Washington state outbreak that was discovered in late February. Notably, none of the observed transmission clusters are epidemiologically linked to the original travel-related cases in the state, suggesting successful early isolation and quarantine. Finally, we use molecular clock analyses to demonstrate a lack of identifiable, widespread cryptic transmission in Arizona prior to the middle of February 2020.
Effects of underlying morbidities on the occurrence of deaths in COVID-19 patients: A systematic review and meta-analysis
Authors: Khan Md. Mostaured Ali , Khan Md. Nuruzzaman , Mustagir Md. Golam , Rana Juwel , Islam Md. Saiful , Kabir Md. Iqbal
Published: May 2020

Background

Coronavirus disease 2019 (COVID-19), the most hectic pandemic of the era, is increasing exponentially and taking thousands of lives worldwide. This study aimed to assess the prevalence of pre-existing morbidities among COVID-19 infected patients and their mortality risks against each type of pre-existing morbidity category.

Methods

To conduct this systematic review and meta-analysis, Medline, Web of Science, Scopus, and CINAHL databases were searched using specified relavent keywords. Further searches were conducted using the reference list of the selected studies, renowned pre-print servers (e.g., medRxiv, bioRixv, SSRN), and relevant journal websites. Studies written in the English language included if those were conducted among COVID-19 patients with and without comorbidities and presented survivor vs. non-survivor counts or hazard/odds of deaths or survivors against types of pre-existing morbidities. Comorbidities reported in the selected studies were grouped into eight categories. The pooled likelihoods of deaths in each category were estimated using a fixed or random-effect model, based on the heterogeneity assessment. Publication bias was assessed by visual inspection of the funnel plot asymmetry and Egger’s regression test. Trim and Fill method was used if there any publication bias was found.

Results

A total of 42 studies included in this study comprised of 39,398 samples. The most common pre-existing morbidities in COVID-19 infected patients were hypertension (36.5%), cardiovascular disease (11.9%), and diabetes (22.0%). The higher likelihood of deaths was found among COVID-19 patients who had pre-existing cardiovascular diseases (OR: 3.32, 95% CI: 2.79-3.95), immune and metabolic disorders (OR: 2.39, 95% CI: 2.00-2.85), respiratory diseases (OR: 2.02, 95% CI: 1.80-2.26), cerebrovascular diseases (OR: 4.12, 95% CI: 3.04-5.58), any types of cancers (OR: 2.22, 95% CI: 1.63-3.03), renal (OR: 3.02, 95% CI: 2.60-3.52), and liver diseases (OR: 1.44, 95% CI: 1.21-1.71).

Conclusions

This study provides evidence of a higher likelihood of deaths among COVID-19 patients against morbidity categories. These findings could potentially help healthcare providers to sort out the most endangered COVID-19 patients by comorbidities, take precautionary measures during hospitalization, assess susceptibility to death, and prioritize their treatment, which could potentially reduce the number of fatalities in COVID-19.
CoViD-19 Epidemic in India and Projections: Is Relief in Sight?
Authors: Indrayan Abhaya , Shukla Shubham
Published: May 2020

Background

Projection of cases and deaths in an epidemic such as CoViD-19 is hazardous and the early projections were way-off the actual pattern. However, we now have actual data for more than 50 consecutive days in India that can be effectively used for projection.

Methods

We closely track the trend and use the same pattern for projection. We call this Empirical Model. We also fit a Theoretical Model based on a Gamma function on the pattern of some of the previous epidemics.

Results

The Empirical Model predicts the peak around the fourth week of May and the near end of the epidemic by the end of June 2020. The maximum number of active cases is likely to be nearly 75,000 during the second week of June. This would mean a peak demand of nearly 15,000 beds and nearly 4000 ventilators. The case-fatality based on those who have reached an outcome was nearly 10% in the first week of May and is likely to remain at this level for some time. Theoretical Model projected a peak of nearly 2500 new cases per day in the second week of May that seems to have been already breached. This model predicts the near end of the epidemic by the middle of July 2020.

Conclusion

With the current trend, the end of the epidemic is in sight with relatively mild consequences in India compared with most other countries.
COVID-19 and Acute Kidney Injury Requiring Kidney Replacement Therapy: A Bad Prognostic Sign
Authors: Shekhar Rahul , Upadhyay Shubhra , Shah Silvi , Kapuria Devika
Published: May 2020

The development of acute kidney injury in patients with COVID-19 is estimated to about 0.5% from earlier studies from China. The incidence of AKI in patients with COIVID-19 in the largest inpatient series in the United States is 22.2%3. Development of AKI requiring kidney replacement therapy in hospitalized patients is a bad prognostic sign. Out of Fifty patients admitted to our hospital with COVID-19 13/50(26%) developed AKI. All patients required hospitalization in intensive care unit care and 12/13 required initiation of kidney replacement therapy. The median age was 41 years (31-85 years) and 50% were men. Common comorbidities were obesity (83%), diabetes (42%), and hypertension (25%). 10/12 (83%) patients were hypoxemic and required oxygen therapy. 11/12 (92%) patients required invasive ventilation. Majority of patients had elevated neutrophils counts (81.8%) and low lymphocyte counts (81.8%). All patients had chest x-ray findings suggestive of pneumonia. 11/12(91.6%) developed septic shock requiring vasopressors. Review of UA showed all patient (9/9) had active urine sediments with blood but 7/9 of them have sterile pyuria. At the end of study period, 1 patient remained hospitalized. 10/11(90%) patients died and one patient was discharged home with resolution of AKI. Median length of stay was 13 days. The exact mechanism of AKI is not well understood in COVID-19 but can be due to acute tubular necrosis due to septic shock because of cytokine storm in severe COVID-19 or direct invasion by SARS-CoV-2 on podocytes and proximal renal tubular cells. Our findings suggest poor prognosis despite continuous kidney replacement therapies in patients who develop AKI with COVID-19.
Cognitive decline associated with anticholinergics, benzodiazepines, and Z-drugs: findings from The Irish Longitudinal Study on Ageing (TILDA)
Authors: Moriarty Frank , Savva George M , Grossi Carlota M , Bennett Kathleen , Fox Chris , Maidment Ian , Loke Yoon K , Steel Nicholas , Kenny Rose Anne , Richardson Kathryn
Published: May 2020

Aim

To estimate the association between patterns of anticholinergic, benzodiazepine, and Z-drug medication use and change in cognitive function in middle-aged and older adults.

Method

This prospective cohort study used data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA), including community-dwelling adults aged ≥50 years followed for up to four years (n=7,027).

Cognitive function was assessed using the Mini Mental State Examination, animal naming test, and word recall tests. Regular medication use was self-reported at baseline and follow-up interviews at two and four years. Pharmacy dispensing claims for a subset (n=2,905) allowed assessment of medication use between interviews and cumulative dosage. Medication use at consecutive waves of TILDA was analysed in relation to change in cognitive function between waves.

Results

Strongly anticholinergic medications (Anticholinergic Cognitive Burden scale 3), benzodiazepines, and Z-drugs were reported by 7.3%, 5.8% and 5.1% of participants respectively at any time during the study. Adjusting for potential confounders, new anticholinergic use between interviews was associated with change in recall score (−1.09, 95% confidence interval −1.64, −0.53) over 2 years compared to non-use, but not with MMSE (0.07; 95%CI -0.21, 0.34) or animal naming (−0.70; −1.43, 0.03). The pharmacy claims analysis was consistent with this finding. Other hypothesised associations were not supported.

Discussion

Except for new use of anticholinergic medications, no other findings supported a risk of cognitive decline over 2-year periods in this middle-aged and older cohort. Patients and prescribers should weigh this potential risk against potential benefits of commencing anticholinergic medications.

What is already known about this subject:

Benzodiazepines, Z-drugs and drugs with anticholinergic activity have been linked with cognitive impairment.

Most evidence is derived from observational studies of older people, with little research on middle-aged adults.

Medication effects may be confounded by indication and these medications are often prescribed for early symptoms of prodromal stages of dementia.

What this study adds:

In this study of adults aged 50 years and older, no consistent pattern of change in cognitive function was associated with the medication exposures tested, except for reduced recall among new users of anticholinergic medications.

Further research in the younger-old adult population should be conducted to confirm these findings.
A Novel Box for Aerosol and Droplet Guarding and Evacuation in Respiratory Infection (BADGER) for COVID-19 and Future Outbreaks
Authors: Le Hau D. , Novak Gordon A. , Janek Kevin C. , Wang Jesse , Huynh Khang N. , Myer Chris , Weinstein Adam , Oberstar Erick L. , Rasmussen Jim , Bertram Timothy H.
Published: May 2020

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected millions and killed hundreds of thousands of people worldwide as of May 2020. Healthcare providers are at increased risks of infection when caring for patients with COVID-19. The mechanism of transmission of SARS-CoV-2 is still not fully understood. However, there is growing evidence for airborne spread, in addition to direct droplet and indirect contact. Here, we report on the design, construction, and testing of the BADGER (Box for Aerosol and Droplet Guarding and Evacuation in Respiratory Infection), an affordable, scalable device that contains droplets and aerosol particles. A semi-sealed environment is created inside the BADGER, which maintains at least twelve-air changes per hour using in-wall vacuum suction, and multiple hand-ports enable healthcare providers to perform essential tasks on a patient’s airway and head. Overall, the BADGER has the potential to contain large droplets and small airborne particles as demonstrated by simulated qualitative and quantitative assessments to provide an additional layer of protection for healthcare providers treating COVID-19 patients.
Healthcare workers preparedness for COVID-19 pandemic in the occupied Palestinian territory: a cross-sectional survey
Authors: Alser Osaid , Alghoul Heba , Alkhateeb Zahra , Hamdan Ayah , Albarqouni Loai , Saini Kiran
Published: May 2020

Background: The coronavirus disease 19 (COVID-19) pandemic threatens to overwhelm the capacity of the vulnerable healthcare system in the occupied Palestinian territory (oPt). Sufficient training of healthcare workers (HCWs) in how to manage COVID-19 and the provision of personal protective equipment (PPE) to enable them to do so will be key tools in allowing oPt to mount a credible response to the crisis.

Methods: A cross-sectional study was conducted using a validated online questionnaire. Data collection occurred between March 30, 2020 and April 12, 2020. The primary outcomes were the availability of PPE and HCWs preparedness in oPt for COVID-19 pandemic and the secondary outcome was regional and hospital differences in oPt in terms of PPE availability and HCWs preparedness.

Results: Of 138 respondents, only 38 HCWs (27.5%) always had access to facemasks when needed and 15 (10.9%) for isolation gowns. The vast majority of HCWs did not find eye protection (n=128, 92.8%), N95 respirators (n=132, 95.7%), and face shields (n=127, 92%) always available. Compared to HCWs in West Bank, those in the Gaza Strip were significantly less likely to have access to alcohol sanitizers (p=0.026) and gloves (p <0.001). On average, governmental hospitals were significantly less likely to have all appropriate PPE measures than non-governmental institutions (p = 0.001). As for preparedness, only 16 (11.6%) surveyed felt confident in dealing with a potential COVID-19 case. With 57 (41.3%) having received any COVID-19 related training and 57 (41.3%) not having a local hospital protocol.

Conclusion: HCWs in oPt are underprepared and severely lacking adequate PPE provision. The lack of local protocols and training has left HCWs' confidence exceedingly low. The lack of PPE provision will exacerbate the spread of COVID-19 and deepen the crisis, whilst putting HCWs at risk.
Lifestyle Risk Factors for Cardiovascular Disease in Relation to COVID-19 Hospitalization: A Community-Based Cohort Study of 387,109 Adults in UK
Authors: Hamer Mark , Kivimaki Mika , Gale Catharine R , Batty George David
Published: May 2020

Aims: It is important to identify characteristics of people who may be most at risk of COVID19 to inform policy and intervention. Little is known about the impact of unhealthy lifestyles including smoking, physical inactivity, obesity, and excessive alcohol intake. We conducted the first large scale general population study on lifestyle risk factors for COVID19.
Methods: Prospective cohort study with national registry linkage to hospitalisation for COVID19. Participants were 387,109 men and women (56.4, SD 8.8 yr; 55.1% women) residing in England from UK Biobank study. Physical activity, smoking, and alcohol intake, were assessed by questionnaire at baseline (2006 to 2010). Body mass index, from measured height and weight, was used as an indicator of overall obesity. Outcome was cases of COVID19 serious enough to warrant a hospital admission from 16 March 2020 to 26 April 2020.
Results: There were 760 COVID19 cases. After adjustment for age, sex and mutually for each lifestyle factor, physical inactivity (Relative risk, 1.32, 95% confidence interval, 1.10, 1.58), smoking (1.42;1.12, 1.79) and obesity (2.05 ;1.68, 2.49) but not heavy alcohol consumption (1.12; 0.93, 1.35) were all related to COVID19. We also found a dose dependent increase in risk of COVID19 with less favourable lifestyle scores, such that participants in the most adverse category had four fold higher risk (4.41; 2.52, 7.71) compared to people with the most optimal lifestyle. This gradient was little affected after adjustment for a wide range of covariates. Based on UK risk factor prevalence estimates, unhealthy behaviours in combination accounted for up to 51% of the population attributable fraction of severe COVID19.
Conclusions and Relevance: Our findings suggest that an unhealthy lifestyle synonymous with an elevated risk of non-communicable disease is also a risk factor for COVID19 hospital admission, accounting for up to half of severe cases. Adopting simple lifestyle changes could lower the risk of severe infection.
Modelling the evolution of COVID-19 in high-incidence European countries and regions: estimated number of infections and impact of past and future intervention measures
Authors: Fernandez-Recio Juan
Published: May 2020

A previously developed mechanistic model of COVID-19 transmission has been adapted and applied here to study the evolution of the disease and the effect of intervention measures in some European countries and territories where the disease had major impact. A clear impact of the major intervention measures on the reproduction number (Rt) has been found in all studied countries and territories, as already suggested by the drop in the number of deaths over time. Interestingly, the impact of such major intervention measures seems to be the same in most of these countries. The model has also provided realistic estimates of the total number of infections, active cases and future outcome. While the predictive capabilities of the model are much more uncertain before the peak of the outbreak, we could still reliably predict the evolution of the disease after a major intervention by assuming the afterwards reproduction number from current study. More challenging is to foresee the long-term impact of softer intervention measures, but this model can estimate the outcome of different scenarios and help planning changes in the implementation of control measures in a given country or region.
rest2vec: Vectorizing the resting-state functional connectome using graph embedding
Authors: Morrissey Zachery D. , Zhan Liang , Ajilore Olusola , Leow Alex D.
Published: May 2020

Resting-state functional magnetic resonance imaging (rs-fmri) is widely used in connectomics for studying the functional relationships between regions of the human brain. rs-fmri connectomics, however, has inherent analytical challenges, such as accounting for negative correlations. In addition, functional relationships between brain regions do not necessarily correspond to their anatomical distance, making the intrinsic geometry of the functional connectome less well understood. Recent techniques in natural language processing and machine learning, such as word2vec, have used embedding methods to map high-dimensional data into meaningful vector spaces. Inspired by this approach, we have developed a graph embedding pipeline, rest2vec, for studying the intrinsic geometry of functional connectomes. We demonstrate how rest2vec uses the phase angle spatial embedding (phase) method with dimensionality reduction techniques to embed the functional connectome into lower dimensions. Rest2vec can also be linked to the maximum mean discrepancy (mmd) metric to assign functional modules of the connectome in a continuous manner, improving upon traditional binary classification methods. Together, this allows for studying the functional connectome such that the full range of correlative information is preserved and gives a more informed understanding of the functional organization of the brain.
Identifying a supramodal language network in human brain with individual fingerprint
Authors: Liu Lanfang , Yan Xin , Li Hehui , Gao Dingguo , Ding Guosheng
Published: May 2020

Where is human language processed in the brain independent of its form? We addressed this issue by analyzing the cortical responses to spoken, written and signed sentences at the level of individual subjects. By applying a novel fingerprinting method based on the distributed pattern of brain activity, we identified a left-lateralized network composed by the superior temporal gyrus/sulcus (STG/STS), inferior frontal gyrus (IFG), precentral gyrus/sulcus (PCG/PCS), and supplementary motor area (SMA). In these regions, the local distributed activity pattern induced by any of the three language modalities can predict the activity pattern induced by the other two modalities, and such cross-modal prediction is individual-specific. The prediction is successful for speech-sign bilinguals across all possible modality pairs, but fails for monolinguals across sign-involved pairs. In comparison, conventional group-mean focused analysis detects shared cortical activations across modalities only in the STG, PCG/PCS and SMA, and the shared activations were found in two groups. This study reveals the core language system in the brain that is shared by spoken, written and signed language, and demonstrates that it is possible and desirable to utilize the information of individual differences for functional brain mapping.
IN SILICOSCREENING AND MOLECULAR DYNAMIC SIMULATION STUDIES OF POTENTIAL SMALL MOLECULE IMMUNOMODULATORS OF THE KIR2DS2 RECEPTOR
Authors: Rowaiye Adekunle Babajide , Olubiyi Jide , Bur Doofan , Uzochukwu Ikemefuna Chijioke , Akpa Alex , Esimone Charles Okechukwu
Published: May 2020

The World Health Organization reports that cancer is one of the most common causes of death worldwide and it accounted for an estimated 9.6 million deaths in 2018. As compared with chemotherapy or radiotherapy, immunotherapy offers a safer, less stressful and selective strategy in the destruction of cancer cells. The killer cell immunoglobulin-like receptor 2DS2 (KIR2DS2) expressed on Natural Killer (NK) cells are involved in signal transduction processes that produce pro-inflammatory cytokines and directly destroy cancer and virally infected cells. The aim of this study is to identify small molecules from natural products that have strong binding affinity with KIR2DS2 and possible bioactivity. A library of small molecule natural compounds obtained from edible African plants was used forin Silicomolecular docking simulations of KIR2DS2 (PDBID: 1m4k) usingPyrx. An arbitrary docking score ≥ −7.0 kcal/mol was chosen as cut off value. Screening for drug-likeness and ligand efficiency was based on the molecular descriptors of the compounds as provided byPubchem. Further screening for saturation, molar refractivity, promiscuity, pharmacokinetic properties, and bioactivity was done usingSWISSADME, PKCSM, andMolinspirationrespectively. The molecular dynamic simulation and analyses was done using theGalaxywebserver which uses the GROMACS software. Analyses of molecular dynamic simulation were done usingGalaxyandMDWEBwebservers. Gibberellin A20 and A29 were obtained as the lead compounds and they show better promise as drug candidates for KIR2DS2 than the standard. It is recommended that the immuno-stimulatory effect of the lead compounds on KIR2DS2 be further investigated.
Performance trade-offs for single- and dual-objective light-sheet microscope designs
Authors: Bishop Kevin W. , Glaser Adam K. , Liu Jonathan T.C.
Published: May 2020

Light-sheet microscopy (LSM) has emerged as a powerful tool for high-speed volumetric imaging of live model organisms and large optically cleared specimens. When designing cleared-tissue LSM systems with certain desired imaging specifications (e.g. resolution, contrast, and working distance), various design parameters must be taken into consideration. In order to elucidate some of the key design trade-offs for LSM systems, we present a diffraction-based analysis of single- and dual-objective LSM configurations where Gaussian illumination is utilized. Specifically, we analyze the effects of the illumination and collection numerical aperture (NA), as well as their crossing angle, on spatial resolution and contrast. Assuming an open-top light-sheet (OTLS) architecture, we constrain these parameters based on fundamental geometric considerations as well as those imposed by currently available microscope objectives. In addition to revealing the performance tradeoffs of various single- and dual-objective LSM configurations, our analysis showcases the potential advantages of a novel, non-orthogonal dual-objective (NODO) architecture, especially for moderate-resolution imaging applications (collection NA of 0.5 to 0.8).
Neural representations of covert attention across saccades: comparing pattern similarity to shifting and holding attention during fixation
Authors: Zhang Xiaoli , Golomb Julie D
Published: May 2020

We can focus visuospatial attention by covertly attending to relevant locations, moving our eyes, or both simultaneously. How does shifting versus holding covert attention during fixation compare with maintaining covert attention across saccades? We acquired fMRI data during a combined saccade and covert attention task. On Eyes-fixed trials, participants either held attention at the same initial location (“hold attention”) or shifted attention to another location midway through the trial (“shift attention”). On Eyes-move trials, participants made a saccade midway through the trial, while maintaining attention in one of two reference frames: The “retinotopic attention” condition involved holding attention at a fixation-relative location but shifting to a different screen-centered location, whereas the “spatiotopic attention” condition involved holding attention on the same screen-centered location but shifting relative to fixation. We localized the brain network sensitive to attention shifts (shift > hold attention), and used multivoxel pattern time course analyses to investigate the patterns of brain activity for spatiotopic and retinotopic attention. In the attention shift network, we found transient information about both whether covert shifts were made and whether saccades were executed. Moreover, in the attention shift network, both retinotopic and spatiotopic conditions were represented more similarly to shifting than to holding covert attention. An exploratory searchlight analysis revealed additional regions where spatiotopic was relatively more similar to shifting and retinotopic more to holding. Thus, maintaining retinotopic and spatiotopic attention across saccades may involve different types of updating that vary in similarity to covert attention “hold” and “shift” signals across different regions.

Significance Statement

To our knowledge, this study is the first attempt to directly compare human brain activity patterns of covert attention (to a peripheral spatial location) across saccades and during fixation. We applied fMRI multivoxel pattern time course analyses to capture the dynamic changes of activity patterns, with specific focus on the critical timepoints related to attention shifts and saccades. Our findings indicate that both retinotopic and spatiotopic attention across saccades produce patterns of activation similar to “shifting” attention in the brain, even though both tasks could be interpreted as “holding” attention by the participant. The results offer a novel perspective to understand how the brain processes and updates spatial information under different circumstances to fit the needs of various cognitive tasks.
NOT ALL ANTIBODIES HAVE BEEN CREATED EQUAL: Antibodies validated for routinely processed tissue seldom apply to frozen tissue sections
Authors: Bolognesi Maddalena M , Mascadri Francesco , Perego Roberto , Bombelli Silvia , Bosisio Francesca M , Cattoretti Giorgio
Published: May 2020

A customized context-dependent validation of antibodies for the prospective use, rather than a general stamp of validity, is required for reproducibility and data validity, besides the need of standardized reagents. In-situ antibody staining is a technique broadly used in experimental settings and human diagnostic practice. The first typically, but not exclusively uses lightly fixed material (cell smears, frozen sections), the second, routinely processed formalin-fixed, paraffin-embedded (FFPE) tissue. Differently from techniques based on tissue extraction, there is little awareness of the context-dependent constraints inherent with either type of in situ staining except that antigen masking associated with routine tissue processing limits the range of useful antibodies. We applied a panel of 126 antibodies validated for FFPE to lightly fixed (acetone, formalin) frozen sections and found that less than 30% performed conservatively with all fixations, 35% preferred one fixation over another, 13% gave non-specific staining, 23% did not stain at all. Individual antibody variegation of the paratope fitness for the differentially fixed antigen may be the cause. Re-validation of established antibody panels is required when applied to sections whose fixation and processing is different from the tissue where they have been initially validated.
The complex optic lobe of dragonflies
Authors: Fabian Joseph M. , el Jundi Basil , Wiederman Steven D. , O’Carroll David C.
Published: May 2020

Dragonflies represent an ancient lineage of visual predators, which last shared a common ancestor with insect groups such as dipteran flies in the early Devonian, 406 million years ago [1,2]. Despite their important evolutionary status, and recent interest in them as a model for complex visual physiology and behavior, the most recent detailed description of the dragonfly optic lobe is itself more than a century old [3]. Many insects process visual information in optic lobes comprising 4 sequential, retinotopically organized neuropils: the lamina, medulla, lobula and a posterior lobula plate devoted to processing information about wide-field motion stimuli [4, 5]. Recent reports suggest that the dragonflies also follow this basic plan, with a divided lobula similar to those of flies, moths and butterflies [6, 7]. Here we refute this claim, showing that dragonflies have an unprecedentedly complex lobula comprising at least 4 sequential synaptic neuropils, in addition to two lobula plate like structures located on opposite sides of the brain. The second and third optic ganglia contain approximately twice as many synaptic layers as any other insect group yet studied. Using intracellular recording and labeling of neurons we further show that the most anterior lobe contains wide-field motion processing tangential neurons similar to those of the posterior lobula plate of dipteran flies. In addition to describing what is probably the most complex and unique optic lobe of any insect to date, our findings provide interesting insights to understanding the evolution of the insect optic lobe and serve as a reminder that the highly studied visual circuits of dipteran flies represent just a single derived form of these brain structures.
Chrna5is essential for a rapid and protected response to optogenetic release of endogenous acetylcholine in prefrontal cortex
Authors: Venkatesan Sridevi , Lambe Evelyn K.
Published: May 2020

Optimal attention performance requires cholinergic modulation of corticothalamic neurons in the prefrontal cortex. These pyramidal cells express specialized nicotinic acetylcholine receptors containing the α5 subunit encoded byChrna5. Disruption of this gene impairs attention, but the advantage α5 confers for the detection ofendogenouscholinergic signaling is unknown. To ascertain this underlying mechanism, we used optogenetics to stimulate cholinergic afferents in prefrontal cortex brain slices from compound-transgenic wild-type andChrna5knockout mice of both sexes. These electrophysiological experiments identify thatChrna5is critical for therapid onsetof the postsynaptic cholinergic response. Loss of α5 slows cholinergic excitation and delays its peak, and these effects are observed in two different optogenetic mouse lines. Disruption ofChrna5does not otherwise perturb the magnitude of the response, which remains strongly mediated by nicotinic receptors and tightly controlled by autoinhibition via muscarinic M2 receptors. However, when conditions are altered to promotesustainedcholinergic receptor stimulation, it becomes evident that α5 also works to protect nicotinic responses againstdesensitization. RescuingChrna5disruption thus presents the double challenge of improving the onset of cholinergic signaling without triggering desensitization. Here, we identify that an agonist for the unorthodox α-α nicotinic binding site can allosterically enhance this cholinergic pathway considered vital for attention. Minimal NS9283 treatment restores the rapid onset of the postsynaptic cholinergic response without triggering desensitization. Taken together, this work demonstrates the advantages of speed and resilience thatChrna5confers on endogenous cholinergic signaling, defining a critical window of interest for cue detection and attentional processing.

Significance statement

The α5 nicotinic receptor subunit (Chrna5) is important for attention, but its advantage in detecting endogenous cholinergic signals is unknown. Here, we show that α5 subunits permit rapid cholinergic responses in prefrontal cortex and protect these responses from desensitization. Our findings clarify whyChrna5is required for optimal attentional performance under demanding conditions. To treat the deficit arising fromChrna5disruption without triggering desensitization, we enhanced nicotinic receptor affinity using NS9283 stimulation at the unorthodox α-α nicotinic binding site. This approach successfully restored the rapid-onset kinetics of endogenous cholinergic neurotransmission. In summary, we reveal a previously unknown role ofChrna5as well as an effective approach to compensate for genetic disruption and permit fast cholinergic excitation of prefrontal attention circuits.