bluuebunny/crossref_metadata_2025 huggingface dataset:
The periodic law of the chemical elements: ‘
The new system of atomic weights which renders evident the analogies which exist between bodies
' []
Authors: Edwards Peter P. , Egdell Russell G. , Fenske Dieter , Yao Benzhen
Published: August 2020

The historical roots, the discovery and the modern relevance of Dmitri Mendeleev's remarkable advance have been the subject of numerous scholarly works. Here, with a brief overview, we hope to provide a link into the contents of this special issue honouring the great scientist. Mendeleev's advance, announced in March 1869, as he put it in 1889, to the ‘…
then youthful Russian Chemical Society…
’, first set out the very basis of the periodic law of the chemical elements, the natural relation between the properties of the elements and their atomic weights. This was, and still is, the centrepiece of a historical journey for chemistry to today's position as a pre-eminent science.

This article is part of the theme issue ‘Mendeleev and the periodic table'.
Metals and non-metals in the periodic table
Authors: Yao Benzhen , Kuznetsov Vladimir L. , Xiao Tiancun , Slocombe Daniel R. , Rao C. N. R. , Hensel Friedrich , Edwards Peter P.
Published: August 2020

The demarcation of the chemical elements into metals and non-metals dates back to the dawn of Dmitri Mendeleev's construction of the periodic table; it still represents the cornerstone of our view of modern chemistry. In this contribution, a particular emphasis will be attached to the question ‘Why do the chemical elements of the periodic table exist either as metals or non-metals under ambient conditions?’ This is perhaps most apparent in the p-block of the periodic table where one sees an almost-diagonal line separating metals and non-metals. The first searching, quantum-mechanical considerations of this question were put forward by Hund in 1934. Interestingly, the very first discussion of the problem—in fact, a pre-quantum-mechanical approach—was made earlier, by Goldhammer in 1913 and Herzfeld in 1927. Their simple rationalization, in terms of atomic properties which confer metallic or non-metallic status to elements across the periodic table, leads to what is commonly called the Goldhammer–Herzfeld criterion for metallization. For a variety of undoubtedly complex reasons, the Goldhammer–Herzfeld theory lay dormant for close to half a century. However, since that time the criterion has been repeatedly applied, with great success, to many systems and materials exhibiting non-metal to metal transitions in order to predict, and understand, the precise conditions for metallization. Here, we review the application of Goldhammer–Herzfeld theory to the question of the metallic versus non-metallic status of chemical elements within the periodic system. A link between that theory and the work of Sir Nevill Mott on the metal-non-metal transition is also highlighted. The application of the ‘simple’, but highly effective Goldhammer–Herzfeld and Mott criteria, reveal when a chemical element of the periodic table will behave as a metal, and when it will behave as a non-metal. The success of these different, but converging approaches, lends weight to the idea of a simple, universal criterion for rationalizing the instantly-recognizable structure of the periodic table where …
the metals are here, the non-metals are there …
The challenge of the metallic and non-metallic states of oxides is also briefly introduced.

This article is part of the theme issue ‘Mendeleev and the periodic table’.
Effect of covid-19 lockdown on child protection medical assessments: a retrospective observational study in Birmingham, UK
Authors: Garstang Joanna , Debelle Geoff , Anand Indu , Armstrong Jane , Botcher Emily , Chaplin Helen , Hallett Nutmeg , Morgans Clare , Price Malcolm , Tan Ern Ern Henna , Tudor Emily , Taylor Julie
Published: August 2020

Objectives

To determine any change in referral patterns and outcomes in children (0-18) referred for child protection medical examination (CPME) during the covid-19 pandemic compared to previous years.

Design

Retrospective observational study, analysing routinely collected clinical data from CPME reports in a rapid response to the pandemic lockdown.

Setting

Birmingham Community Healthcare NHS Trust, which provides all routine CPME for Birmingham, England, population 1.1 million including 288,000 children.

Participants

Children aged under 18 years attending CPME during an 18 week period from late February to late June during the years 2018, 2019, and 2020.

Main Outcome Measures

Numbers of referrals, source of disclosure and outcomes from CPME

Results

There were 78 CPME referrals in 2018, 75 in 2019 and 47 in 2020, this was a 39.7% (95%CI 12.4-59.0) reduction in referrals from 2018 to 2020, and a 37.3% (95%CI 8.6-57.4) reduction from 2019 to 2020. There were fewer CPME referrals initiated by school staff in 2020, 12(26%) compared to 36 (47%) and 38 (52%) in 2018 and 2019 respectively. In all years 75.9% of children were known to social care prior to CPME, and 94% of CPME concluded that there were significant safeguarding concerns.

Conclusions

School closure due to covid-19 may have harmed children as child abuse has remained hidden. There needs to be either mandatory attendance at schools in future or viable alternatives found. There may be a significant increase in safeguarding referrals when schools fully re-open as children disclose the abuse they have experienced at home.

Article summary: Strengths and Limitations of the Study

This is a highly robust study: we obtained CPME reports for 97% of CPME referrals during the study period.

We ensured consistency of data extraction by double reviewing every report, with further consensus discussions for the few cases that raised uncertainties.

The team extracting the data comprised highly experienced paediatricians with expertise in child abuse.

One weakness is that we only considered minor injuries from outpatient CPME, excluding those admitted to hospital, so our findings do not include those with more serious NAI, however they would be taken to hospital for treatment due to the severity of their injuries.
Investigation of pooling strategies using clinical COVID-19 samples for more efficient diagnostic testing
Authors: Adikari Samantha H. , Alipio Lyon Emily Z. , Hollander Attelia D. , Deshpande Alina , Hong-Geller Elizabeth
Published: August 2020

When testing large numbers of clinical COVID-19 samples for diagnostic purposes, pooling samples together for processing can offer significant reductions in the materials, reagents, time, and labor needed. We have evaluated two different strategies for pooling independent nasopharyngeal swab samples prior to testing with an EUA-approved SARS-CoV-2 RT-qPCR diagnostic assay. First, in the Dilution Study, we assessed the assay's ability to detect a single positive clinical sample diluted in multiple negative samples before the viral RNA extraction stage. We observed that positive samples with Ct values at ~30 can be reliably detected in pools of up to 30 independent samples, and positive samples with Ct values at ~35 can be detected in pools of 5 samples. Second, in the Reloading Study, we assessed the efficacy of reloading QIAamp viral RNA extraction columns numerous times using a single positive sample and multiple negative samples. We determined that one RNA extraction column can be reloaded with up to 20 clinical samples (1 positive and 19 negatives) sequentially without any loss of signal in the diagnostic assay. Furthermore, we found there was no significant difference in assay readout whether the positive sample was loaded first or last in a series of 20 samples. These results demonstrate that different pooling strategies can lead to increased process efficiencies for COVID-19 clinical diagnostic testing.
Distinct microRNA signature in human serum and germline after childhood trauma
Authors: Jawaid Ali , Kunzi Marina , Mansoor Mahgul , Khan Zain Yar , Abid Anooshay , Taha Muhammad , Rigotti Serena , Thumfart Kristina , Faisal Saba , Chughtai Omar , Mansuy Isabelle M
Published: August 2020

Traumatic experiences during childhood can persistently alter mental and physical health in humans and have been implicated in transmission of symptoms to the progeny in animal models. Molecular evidence from these models implicates epigenetic/non-genetic factors, such as microRNAs (miRNAs), in the expression of trauma-induced symptoms and their transmission to the offspring. To confirm these findings in humans, we assembled three cohorts of subjects exposed to childhood trauma and examined selected miRNAs linked to psychological and pathophysiological manifestations of childhood trauma. Children aged 7-12 years (n = 72, control n = 30) exposed to paternal loss and maternal separation (PLMS) exhibited increase in two miRNAs, miR-16 and miR-375 in serum and reduced level of high-density lipoproteins (HDL) compared to control children. Comparable miRNA changes were observed in serum of adult men aged 18-25 years (n = 13, control n = 17) who had been exposed to PLMS at a young age. Finally, the same miRNAs were altered in sperm of adult men aged 21-50 years (n = 23, control n = 35) exposed to two or more significant traumatic events in childhood, assessed retrospectively using the standardized childhood trauma questionnaire (CTQ). In vitro experiments show that regulation of these miRNA involves the HDL receptor SRB-1, suggesting a link between trauma-associated miRNAs and metabolic alterations.
Challenges and proposed solutions in making clinical research on COVID-19 ethical. A status quo analysis across German research ethics committees
Authors: Faust Alice , Sierawska Anna , Krüger Katharina , Wisgalla Anne , Hasford Joerg , Strech Daniel
Published: August 2020

Background

In the course of the COVID-19 pandemic, the biomedical research community’s attempt to focus the attention on fighting COVID-19, led to several challenges within the field of research ethics. However, we know little about the practical relevance of these challenges for Research Ethics Committees (RECs).

Methods

We conducted a qualitative survey across all 52 German RECs on the challenges and potential solutions with reviewing proposals for COVID-19 studies. We de-identified the answers and applied thematic text analysis for the extraction and synthesis of challenges and potential solutions that we grouped under established principles for clinical research ethics.

Results

We received an overall response rate of 42%. The 22 responding RECs reported that they had assessed a total of 441 study proposals on COVID-19 until 21 April 2020. For the review of these proposals the RECs indicated a broad spectrum of challenges regarding i) social value (e.g. lack of coordination), ii) scientific validity (e.g. provisional study planning), iii) favourable risk-benefit ratio (e.g. difficult benefit assessment), iv) informed consent (e.g. strict isolation measures), v) independent review (e.g. lack of time), vi) fair selection of trial participants (e.g. inclusion of vulnerable groups), and vii) respect for study participants (e.g. data security). Mentioned solutions ranged from improved local/national coordination, over guidance on modified consent procedures, to priority setting across clinical studies.

Conclusions

RECs are facing a broad spectrum of pressing challenges in reviewing COVID-19 studies. Some challenges for consent procedures are well known from research in intensive care settings but are further aggravated by infection measures. Other challenges such as reviewing several clinical studies at the same time that potentially compete for the recruitment of in-house COVID-19 patients are unique to the current situation. For some of the challenges the proposed solutions in our survey could relatively easy be translated into practice. Others need further conceptual and empirical research. Our findings together with the increasing body of literature on COVID-19 research ethics, and further stakeholder engagement should inform the development of hands-on guidance for researchers, funders, RECs, and further oversight bodies.
Automated molecular testing of saliva for SARS-CoV-2 detection
Authors: Matic Nancy , Lawson Tanya , Ritchie Gordon , Stefanovic Aleksandra , Leung Victor , Champagne Sylvie , Romney Marc G. , Lowe Christopher F.
Published: August 2020

With surging global demand for increased SARS-CoV-2 testing capacity, clinical laboratories seek automated, high-throughput molecular solutions, particularly for specimen types which do not rely upon supply of specialized collection devices or viral transport media (VTM). Saliva was evaluated as a diagnostic specimen for SARS-CoV-2 using the cobas® SARS-CoV-2 Test on the cobas® 6800 instrument. Saliva specimens submitted from various patient populations under investigation for COVID-19 from March-July 2020 were processed in the laboratory with sterile phosphate-buffered saline in a 1:2 dilution and vortexed with glass beads. The processed saliva samples were tested using a commercial assay for detection of the SARS-CoV-2 E gene (LightMix®) in comparison to the cobas® SARS-CoV-2 Test. 22/64 (34.4%) of the saliva samples were positive for SARS-CoV-2. Positive and negative concordance between the LightMix® and cobas® assays were 100%. There was no cross-contamination of samples observed on the cobas® 6800. The overall invalid rate for saliva on the cobas® 6800 (1/128, 0.78%) was similar to the baseline invalid rate observed for nasopharyngeal swabs/VTM and plasma samples. Saliva is a feasible specimen type for SARS-CoV-2 testing on the cobas® 6800, with potential to improve turnaround time and enhance testing capacity.
Local protection bubbles: an interpretation of the decrease in the velocity of coronavirus’s spread in the city of São Paulo
Authors: Pinto José Paulo Guedes , Magalhães Patrícia Camargo , Figueiredo Gerusa Maria , Alves Domingos , Segura-Angel Diana Maritza
Published: August 2020

After four months of dealing with the pandemic, the city of São Paulo entered a phase of relaxed social-distancing measures in July 2020, and saw its social isolation rate fall at the same time as the number of cases, deaths, and hospital bed occupation declined. We use a calibrated multi-agent model to describe these dynamics. We assert here that this phenomenon can be understood as the result of local protective bubbles formed in the city’s sub-environments at the same time that there was an exhaustion of contagion networks. Both reduce the velocity of the virus’s spread, causing temporary reductions in the epidemic curve, albeit in an unstable equilibrium. These local bubbles can burst anytime and anywhere due to the reintroduction of a few infected people at the same time that there is a reduction in non-pharmaceutical interventions (NPI), such as social-distancing practices. It is important to stress that this hypothesis aligns with the dynamics of the virus’s spread observed so far, without needing ad hoc suppositions about natural collective immunity thresholds or heterogeneity in the population’s transmission rate, which come with the risk of making mistaken predictions that may could lead to the loss of many lives. The safe way to move ahead is to continue doing all we can to avoid new infections until a vaccine is found that properly and safely creates herd immunity.
To what extent physical distancing and other COVID-19 preventive measures being implemented among people in Arba Minch town, Southern Ethiopia: exploring evidences for an urgent call for action?
Authors: Asfaw Mekuria Asnakew , Yohannes Tsegaye , Churko Chuchu , Bekele Alemayehu , Wegayehu Teklu
Published: August 2020

Background

The number of confirmed Coronavirus disease 2019 (COVID-19) cases surge substantially in resource-poor settings within the fragile health system. Since there are no proven vaccine and treatment in place against the disease, controlling strategy mainly rely on preventive measures. However, data on the extent of implementing physical distancing and other preventive measures were under estimated. This study, therefore, investigated these gaps among people in Arba Minch town, southern Ethiopia.

Methods

We conducted a community based cross-sectional study in Arba Minch town; from 15-30 June 2020. Data were collected using interviewer administered questionnaire and checklist. Then, data were cleaned, coded and entered to EpiData version 4.4.2, and exported to SPSS version 20 for analysis.

Results

Of the total participants (459), 43.6% achieved above the mean score (6±1.97) on preventive measures of COVID-19. Only 29.8% of participants kept the recommended physical distance, and surprisingly, in all public gathering places the distance was not kept totally. In addition, of the total participants, only 37.7% had face-mask use practice; 20.5% had hand sanitizer use practice, and 13.1% were measuring their body temperature every two weeks. Moreover, 42.5% of participants avoided attendance in public gatherings; 44.7% stopped touching their nose, eye and mouth; 55.6% practiced stay-at-home; and 60% had frequent hand washing practice. Majority of participants (66.7%) practiced covering their mouth and nose while coughing or sneezing; 68.2% had treatment seeking behavior if they experience flue like symptoms; 69.1% practiced isolating themselves while having flue like symptoms; and 89.3% avoided hand shaking.

Conclusions

The findings of this study suggest that physical distancing and other COVID-19 preventive measures were inadequately implemented among people in Arba Minch town. Thus, an urgent call for action is demanding to mitigate the spread of the COVID-19 as early as possible before it brings a devastating impact.
Data Resource Profile: Understanding the patterns and determinants of health in South Asians - South Asia Biobank
Authors: Song Peige , Gupta Ananya , Goon Ian Y , Hasan Mehedi , Mahmood Sara , Page Polly , Pradeepa Rajendra , Siddiqui Samreen , Silva Wnurinham , Aarthi Garudam R , Afzal Saira , Day Sophie E , Frost Gary S , Holmes Bridget A , Kamalesh Rajan , Kusuma Dian , Miraldo Marisa , Pineda Elisa , Hersch Fred , Rai Baldeesh K , Sarker Malabika , Sassi Franco , Valabhji Jonathan , Wareham Nick J , Ahmed Sajjad , Anjana Ranjit M , Brage Soren , Forouhi Nita G , Jha Sujeet , Kasturiratne Anuradhani , Katulanda Prasad , Khawaja Khadija I , Loh Marie , Mridha Malay K , Wickremasinghe Ananda R , Kooner Jaspal S , Chambers John C
Published: August 2020

Background and aims

This paper describes the data resource profile of South Asia Biobank (SAB), which was set up in South Asia from November 2018 to March 2020, to identify the risk factors and their complex interactions underlying the development of type-2 diabetes mellitus, cardiovascular disease and other chronic diseases in South Asians.

Data resource basics

This cross-sectional population-based study has recruited 52713 South Asian adults from 118 surveillance sites at five centres of excellence in South Asia (Bangladesh, North India, South India, Pakistan and Sri Lanka). Structured assessments of participants included six complementary domains: i). Registration and consent; ii). Questionnaire (information on behavioural risk factors, personal and family medical history, medications, socioeconomic status); iii). Physical measurements (height, weight, waist and hip circumference and bio-impedance for body fat composition, blood pressure, cardiac evaluation, retinal photography, respiratory evaluation); iv). Biological samples (blood and urine); v). Physical activity monitoring and vi). Dietary intake by a 24-hour recall. Aliquots of whole blood, serum, plasma, and urine were put into storage at −80°C for further analysis.

Key results

The prevalence of obesity is 6.6% in Bangladesh, 19.7% in India, 33.9% in Pakistan and 15.7% in Sri Lanka. The prevalence of diabetes is 11.5%, 27.7%, 25.3%, and 24.8%, and the prevalence of hypertension is 26.7%, 36.9%, 44.5%, 35.0% in Bangladesh, India, Pakistan and Sri Lanka respectively.

Collaboration and data access

SAB is the first comprehensive biobank of South Asian individuals. Collected data are available to the global scientific community upon request.
OpenSAFELY: Do adults prescribed non-steroidal anti-inflammatory drugs have an increased risk of death from COVID-19?
Authors:   The OpenSAFELY Collaborative, Wong Angel YS , MacKenna Brian , Morton Caroline E , Schultze Anna , Walker Alex J , Bhaskaran Krishnan , Brown Jeremy P , Rentsch Christopher T , Williamson Elizabeth , Drysdale Henry , Croker Richard , Bacon Seb , Hulme William , Bates Chris , Curtis Helen J , Mehrkar Amir , Evans David , Inglesby Peter , Cockburn Jonathan , McDonald Helen I , Tomlinson Laurie , Mathur Rohini , Wing Kevin , Forbes Harriet , Parry John , Hester Frank , Harper Sam , Evans Stephen JW , Smeeth Liam , Douglas Ian J , Goldacre Ben
Published: August 2020

Importance

There has been speculation that non-steroidal anti-inflammatory drugs (NSAIDs) may negatively affect coronavirus disease 2019 (COVID-19) outcomes, yet clinical evidence is limited.

Objective

To assess the association between NSAID use and deaths from COVID-19 using OpenSAFELY, a secure analytical platform.

Design

Two cohort studies (1stMarch-14thJune 2020).

Setting

Working on behalf of NHS England, we used routine clinical data from >17 million patients in England linked to death data from the Office for National Statistics.

Participants

Study 1: General population (people with an NSAID prescription in the last three years). Study 2: people with rheumatoid arthritis/osteoarthritis.

Exposures

Current NSAID prescription within the 4 months before 1stMarch 2020.

Main Outcome and Measure

We used Cox regression to estimate hazard ratios (HRs) for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, adjusting for age, sex, comorbidities and other medications.

Results

In Study 1, we included 535,519 current NSAID users and 1,924,095 non-users in the general population. The crude HR for current use was 1.25 (95% CI, 1.07–1.46), versus non-use. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR, 0.95, 95% CI, 0.80–1.13) in the fully adjusted model.

In Study 2, we included 1,711,052 people with rheumatoid arthritis/osteoarthritis, of whom 175,631 (10%) were current NSAID users. The crude HR for current use was 0.43 (95% CI, 0.36–0.52), versus non-use. In the fully adjusted model, we observed a lower risk of COVID-19 related death (HR, 0.78, 95% CI, 0.65–0.94) associated with current use of NSAID versus non-use.

Conclusion and Relevance

We found no evidence of a harmful effect of NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about therapeutic use of NSAIDs.
Examining face-mask usage as an effective strategy to control COVID-19 spread
Authors: Catching Adam , Capponi Sara , Yeh Ming Te , Bianco Simone , Andino Raul
Published: August 2020

COVID-19’s high virus transmission rates have caused a pandemic that is exacerbated by the high rates of asymptomatic and presymptomatic infections. These factors suggest that face masks and social distance could be paramount in containing the pandemic. We examined the efficacy of each measure and the combination of both measures using an agent-based model within a closed space that approximated real-life interactions. By explicitly considering different fractions of asymptomatic individuals, as well as a realistic hypothesis of face masks protection during inhaling and exhaling, our simulations demonstrate that a synergistic use of face masks and social distancing is the most effective intervention to curb the infection spread. To control the pandemic, we show that practicing social distance is less efficacious than the widespread usage of face masks and that wearing face masks provides optimal protection even if only a small portion of the population comply with social distance. Finally, the face mask effectiveness in curbing the viral spread is not reduced if a large fraction of population is asymptomatic. Our findings have important implications for policies that dictate the reopening of social gatherings.

Author summary

The COVID-19 outbreak has created an enormous burden on the worldwide population. Among the various ways of preventing the spread of the virus, face masks have been proposed as a main way of reducing transmission. Yet, the interplay between the usage of face mask and other forms of Non-Pharmaceutical Intervention is still not completely clear. In this paper we introduce a stochastic individual-based model which aims at producing realistic scenarios of disease spread when mask wearing with different inward and outward efficacy and social distancing are enforced. The model elucidates the conditions that makes the two forms of intervention synergistic in preventing the spread of the disease.
Circulating-tumor DNA from Two Types of Blood Collection Tubes for Monitoring Tumor Burden Validated with Esophageal Squamous Cell Carcinoma Patients
Authors: Endo Fumitaka , Iwaya Takeshi , Sasaki Yasushi , Chiba Takehiro , Yaegashi Mizunori , Kume Kohei , Sato Kei , Arisue Atsuhiro , Kawagishi Ryoko , Matuo Teppei , Akiyama Yuji , Sasaki Akira , Suzuki Yuji , Tokino Takashi , Masuda Mari , Yamada Tesshi , Nakagawa Hidewaki , Nishizuka Satoshi S.
Published: August 2020

Objective

To evaluate long-term whole blood (WB) storage at room temperature (RT), plasma and peripheral blood mononuclear cell (PBMC) DNA was collected simultaneously using BD Vacutainer® CPTTM Mononuclear Cell Preparation Tubes (CPT) and Streck Cell-Free DNA Blood Collection Tubes (BCT®).

Methods

Plasma DNA was isolated from both types of tubes at various time points at RT. DNA from PBMCs was extracted using CPT from WB stored in BCT. The extracted DNA was used to monitor esophageal cancer treatment.

Results

BCT maintained steady levels of plasma DNA for up to nine days. After transfer of BCT-stored WB to CPT, PBMC-DNA were yielded with suitable quality for up to seven days. ctDNA from esophageal cancer patients carrying TP53 mutations reflected treatment efficacy.

Conclusion

BCT/CPT combinatory procedure allows storage of blood samples for up to seven days at RT for valid clinical assays using ctDNA.
First report of tocilizumab use in a cohort of Latin American patients hospitalized for severe COVID-19 pneumonia
Authors: Valenzuela Omar , Ibáñez Sebastián , Poli María , Roessler Patricia , Aylwin Mabel , Roizen Gigia , Iruretagoyena Mirentxu , Agar Vivianne , Donoso Javiera , Fierro Margarita , Montes José
Published: August 2020

Introduction/objectives

An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19.

Methods

Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of tocilizumab. Patients with progressive ventilatory impairment and evidence of a hyperinflammatory state despite usual treatment received tocilizumab 8 mg/kg intravenous (maximum dose 800 mg), in addition to standard treatment. The use and time of use of mechanical ventilation (MV), the change of the Alveolar-arterial (A-a) gradient, of the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and of inflammation laboratory parameters after 72 hours of tocilizumab use was evaluated.

Results

29 patients received tocilizumab. 93.1% were men, 37.9% were obese, and 34.5% had hypertension. Of the 20 patients who were not on MV when receiving tocilizumab, 11 required non-invasive MV, for an average of five days, and one of them required intubation. A-a gradient, PaO2/FiO2, and inflammation parameters improved significantly. A better lymphocyte count, which improved significantly after tocilizumab use, was significantly associated with less use of MV. Five patients presented positive culture samples after tocilizumab, three being of clinical significance. A lower lymphocyte count was associated with having a positive culture. No other significant adverse events were seen.

Conclusion

Our study suggests the utility and shows the safety of tocilizumab use in COVID-19 patients who have respiratory failure and evidence of hyperinflammation. Lymphocyte improvement was a predictor of good response.

Key-points

The use of tocilizumab in patients with severe COVID-19 was safe.

Most of the patients presented a good response in terms of ventilatory and inflammatory parameters.

Lymphocyte improvement after using tocilizumab was the main predictor of a good outcome.
Comprehensive analysis of the key epidemiological parameters to evaluate the impact of BCG vaccination on COVID-19 pandemic
Authors: Datta Niloy R. , Datta Sneha
Published: August 2020

Globally, the heterogenous coronavirus disease 2019 (COVID-19) case fatality rate (CFR) could be influenced by various epidemiological parameters. Identifying these could help formulate effective public health strategies. Incidence and mortality of COVID-19 for each of the 220 countries as on July 30, 2020 were evaluated against key epidemiological variables, namely - BCG vaccination (ongoing vs. discontinued/never undertaken), %population aged ≥65 years, incidences of ischemic heart disease (IHD), hypertensive heart disease (HHD), cancer, malaria, and diabetes; human development index (HDI) and population density. These were retrieved from the public domains of WHO, UN, World Bank and published reports. The COVID-19 CFRs ranged between 0.0% and 28.3% (mean ± SD: 3.05% ± 3.48). The influence of the individual epidemiological parameters on CFR were evaluated through the event rate estimations. A significantly lower event rate was observed in countries with ongoing BCG vaccination program (ER: with vs without ongoing BCG vaccination: 0.020 vs 0.034, p<0.001). The type of BCG strains used also influenced the ER; this being 0.018, 0.031 and 0.019 for early, late and mixed strains respectively (p=0.008). The epidemiological variables significantly associated with higher COVID-19 event rate were countries with higher %population aged ≥65 years (p<0.001), greater incidence of IHD (p<0.001) and cancer (p=0.003) and better HDI (p=0.003). Incidences of malaria, HHD and diabetes along with population density had no significant impact on COVID-19 CFR. Further, BCG vaccination significantly lowered the COVID-19 ER in each of the high-risk population subgroups - countries with >7.1% population aged ≥65 years (p=0.008), >0.737 HDI (p=0.001), IHD >1171/105 population (p=0.004) and cancer incidence >15726 (p<0.001). The results supports BCG induced “trained immunity” leading to heterologous immunoprotection against COVID-19. Thus BCG vaccination with early strains could provide a cost-effective prophylaxis, especially in high-risk individuals and bridge the gap till an effective vaccine against SARS-CoV-2 is freely available globally.
Assessing the risk of COVID-19 importation and the effect of quarantine
Authors: Arino Julien , Bajeux Nicolas , Portet Stéphanie , Watmough James
Published: August 2020

Objectives

During the early stage of COVID-19 spread, many governments and regional jurisdictions put in place travel restrictions and imposed quarantine after arrivals in an effort to slow down or stop the importation of cases. At the same time, they implemented non-pharmaceutical interventions (NPI) to curtail local spread. We assess the risk of importation of COVID-19 in locations that are at that point without infection or where local chains of transmission have extinguished, and evaluate the role of quarantine in this risk.

Methods

A stochastic SLIAR epidemic model is used. The effect of the rate, size, and nature of importations is studied and compared to that of NPI on the risk of importation-induced local transmission chains. The effect of quarantine on the rate of importations is assessed, as well as its efficacy as a function of its duration.

Results

The rate of importations plays a critical role in determining the risk that case importations lead to local transmission chains, more so than local transmission characteristics, i.e., strength of NPI. The latter influences the severity of the outbreaks. Quarantine after arrival in a location is an efficacious way to reduce the rate of importations.

Conclusions

Locations that see no or low level local transmission should ensure that the rate of importations remains low. A high level of compliance with post-arrival quarantine followed by testing achieves this objective with less of an impact than travel restrictions or bans.
SelectStitch: Automated Frame Segmentation and Stitching to Create Composite Images from Otoscope Video Clips
Authors: Binol Hamidullah , Moberly Aaron C. , Niazi M. Khalid Khan , Essig Garth , Shah Jay , Elmaraghy Charles , Teknos Theodoros , Taj-Schaal Nazhat , Yu Lianbo , Gurcan Metin N.
Published: August 2020

Background and Objective

The aim of this study is to develop and validate an automated image segmentation-based frame selection and stitching framework to create enhanced composite images from otoscope videos. The proposed framework, called SelectStitch, is useful for classifying eardrum abnormalities using a single composite image instead of the entire raw otoscope video dataset.

Methods

SelectStitch consists of a convolutional neural network (CNN) based semantic segmentation approach to detect the eardrum in each frame of the otoscope video, and a stitching engine to generate a high-quality composite image from the detected eardrum regions. In this study, we utilize two separate datasets: the first one has 36 otoscope videos that were used to train a semantic segmentation model, and the second one, containing 100 videos, which was used to test the proposed method. Cases from both adult and pediatric patients were used in this study. A configuration of 4-levels depth U-Net architecture was trained to automatically find eardrum regions in each otoscope video frame from the first dataset. After the segmentation, we automatically selected meaningful frames from otoscope videos by using a pre-defined threshold, i.e., it should contain at least an eardrum region of 20% of a frame size. We have generated 100 composite images from the test dataset. Three ear, nose, and throat (ENT) specialists (ENT-I, ENT-II, ENT-III) compared in two rounds the composite images produced by SelectStitch against the composite images that were generated by the base processes, i.e., stitching all the frames from the same video data, in terms of their diagnostic capabilities.

Results

In the first round of the study, ENT-I, ENT-II, ENT-III graded improvement for 58, 57, and 71 composite images out of 100, respectively, for SelectStitch over the base composite, reflecting greater diagnostic capabilities. In the repeat assessment, these numbers were 56, 56, and 64, respectively. We observed that only 6%, 3%, and 3% of the cases received a lesser score than the base composite images, respectively, for ENT-I, ENT-II, and ENT-III in Round-1, and 4%, 0%, and 2% of the cases in Round-2.

Conclusions

Frame selection improves the diagnostic quality of composite images from otoscope video clips.
Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18 and SARS-CoV-2-specific IgA
Authors: Tao Wanyin , Zhang Guorong , Wang Xiaofang , Guo Meng , Zeng Weihong , Xu Zihao , Liu Lianxin , Zhang Kaiguang , Wang Yucai , Ma Xiaoling , Chen Zhengxu , Jin Tengchuan , Weng Jianping , Zhu Shu
Published: August 2020

The current global COVID-19 pandemic is caused by beta coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which already infected over 10 million and caused 500 thousand deaths by June 2020. Overproduction of cytokines triggered by COVID-19 infection, known as "cytokine storm", is a highly risk factor associated with disease severity. However, how COVID-19 infection induce cytokine storm is still largely unknown. Accumulating in vitro and in vivo evidence suggests that gut is also susceptible to COVID19 infection: Human intestinal organoids, an in vitro model which mimic the specific cell type and spatial structure of the intestine, were susceptible to SARS-CoV2 infection; A significant fraction of patients reported gut symptoms; Viral RNA may persist for more than 30 days and infectious virus could be isolated in fecal samples. The gastrointestinal tract is the primary site of interaction between the host immune system with symbiotic and pathogenic microorganisms. The bacteria resident in our gastrointestinal tract, known as gut microbiota, is important to maintain the homeostasis of our immune system. While imbalance of gut microbiota, or dysbiosis, is associated with multiple inflammation diseases5. It's possible that SARS-CoV-2 infection may lead to alternation of gut microbiota thus worsen the host symptom. IL-18 is a proinflammatory cytokine produced multiple enteric cells, including intestinal epithelial cells (IECs), immune cells as well as enteric nervous system, and was shown to increase in the serum of COVID-19 patients. Immunoglobin A (IgA) is mainly produced in the mucosal surfaces, in humans 40-60mg kg-1 day-1 than all other immunoglobulin isotypes combined, and at least 80% of all plasma cells are located in the intestinal lamina propria. Recent study showed that SARS-CoV-2 specific IgA in the serum is positively correlate with the disease severity in COVID-19 patients11. Here we investigated the alterations of microbiota in COVID-19 patients, and its correlation with inflammatory factor IL-18 and SARS-CoV2 specific IgA.
Obesity and Smoking as Risk Factors for Invasive Mechanical Ventilation in COVID-19 Respiratory Failure: a Retrospective, Observational Cohort Study
Authors: Monteiro Ana C. , Suri Rajat , Emeruwa Iheanacho O. , Stretch Robert J. , Cortes-Lopez Roxana Y. , Sherman Alexander , Lindsay Catherine C. , Fulcher Jennifer A. , Goodman-Meza David , Sapru Anil , Buhr Russell G. , Chang Steven , Wang Tisha , Qadir Nida
Published: August 2020

Purpose

To describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV).

Materials and Methods

A retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV.

Results

Our cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis.

Conclusions

Obesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.
Clinical characteristics and Outcomes of 500 patients with COVID Pneumonia – Results from a Single center (Southend University Hospital)
Authors: Koduri Gouri , Gokaraju Sriya , Darda Maria , Warrier Vinod , Duta Irina , Hayes Fiona , Sayed Iman El , Ahmed Yasser
Published: August 2020

Objectives

To characterise the clinical features of hospitalised COVID-19 patients in a single centre during the first epidemic wave and explore potential predictive variables associated with outcomes such as mortality and the need for mechanical ventilation, using baseline clinical parameters.

Methodology

We conducted a retrospective review of electronic records for demographic, clinical and laboratory data, imaging and outcomes for 500 hospitalised patients between February 20thand May 7th2020 from Southend University Hospital, Essex, UK. Multivariate logistic regression models were used to identify risk factors relevant to outcome.

Results

The mean age of the cohort admitted to hospital with Covid-19, was 69.4 and 290 (58%) were over 70. The majority were Caucasians, 437 (87%) with ≤2 comorbidities 280(56%). Most common were hypertension 186(37%), Cardiovascular disease 178(36%) and Diabetes 128 (26%), represented in a larger proportion on the mortality group. Mean CFS was 4 with Non - Survivors had significantly higher CFS 5 vs 3 in survivors, p<0.001. In addition, Mean CRP was significantly higher 150 vs 90, p<0.001 in Non-Survivors. We observed the baseline predictors for mortality were age, CFS and CRP.

Conclusions

In this single centre study, older and frailer patients with more comorbidities and a higher baseline CRP and creatinine were risk factors for worse outcomes. Integrated frailty and age-based risk stratification are essential, in addition to monitoring SFR (Sp02/Fi02) and inflammatory markers throughout the disease course to allow for early intervention to improve patient outcomes.
Extracting novel antimicrobial emergence events from scientific literature and medical reports
Authors: Mendelsohn Emma , Ross Noam , White Allison M. , Whiting Karissa , Basaraba Cale , Madubuonwu Brooke Watson , Johnson Erica , Dualeh Mushtaq , Matson Zach , Dattaray Sonia , Ezeokoli Nchedochukwu , Lieberman Melanie Kirshenbaum , Kotcher Jacob , Maher Samantha , Zambrana-Torrelio Carlos , Daszak Peter
Published: August 2020

Despite considerable global surveillance of antimicrobial resistance (AMR), data on the global emergence of new resistance genotypes in bacteria has not been systematically compiled. We conducted a study of English-language scientific literature (2006-2017) and disease surveillance reports (1994-2017) to identify global events of novel AMR emergence (first clinical reports of unique drug-bacteria resistance combinations). We screened 24,966 abstracts and reports, ultimately identifying 1,773 novel AMR emergence events from 294 articles. Events were reported in 66 countries, with most events in the United States (152), India (129), and China (128). The most common bacteria demonstrating new resistance were Klebsiella pneumoniae (352) and Escherichia coli (218). Resistance was most common against antibiotic drugs imipenem (89 events), ciprofloxacin (85) and ceftazidime (82). We provide an open-access database of emergence events with standardized fields for bacterial species, drugs, location, and date, and we discuss guidelines and caveats for data analysis. This database may be broadly useful for understanding rates and patterns of AMR evolution, identifying global drivers and correlates, and targeting surveillance and interventions.
The cost-effectiveness of common strategies for the prevention of transmission of SARS-CoV-2: a flexible policy online platform
Authors: Zafari Zafar , Goldman Lee , Kovrizhkin Katia , Muennig Peter
Published: August 2020

Background

The added value of interventions to prevent the transmission of SARS-CoV-2 among university affiliates is uncertain but needed as universities attempt to remain open.

Methods

We use a decision-analytic simulation to examine the cost-effectiveness of common interventions to reduce SARS-CoV-2 transmission. We use Columbia University for reference values but our approach centers around an online model that allows users to tailor the model and interventions to their local conditions and existing strategies. All interventions are compared relative to implementing the Centers for Disease Control and Prevention (CDC) guidelines alone. Results. At prevalence rate of actively infectious cases of COVID-19 in the community surrounding the university of 0.1%, using a symptom-checking mobile application is cost-saving relative to CDC guidelines alone and the university can expect to remain open. At a prevalence of 1%, standardizing masks will be cost-saving. At a prevalence rate of 2%, thermal imaging cameras cost $965,070 (95% credible interval [CrI] = $198,821, $2.15 million)/quality-adjusted life year (QALY) gained. One-time testing on entry costs $1.08 million (95% CrI = $170,703, $3.33 million)/QALY gained. Weekly testing costs $820,119 (95% CrI = $452,673, $1.68 million)/QALY gained. Upgrades to ventilation systems or installation of far-ultraviolet C lighting systems will be cost-effective at a willingness-to-pay threshold of $200,000/QALY gained only if aerosols account for 86-90% of all on-campus transmission of SARS-CoV-2.

Conclusions

The value of interventions to prevent transmission of SARS-CoV-2 vary greatly with the prevalence rate of actively infectious cases of COVID-19 in the community surrounding the university.

Key Points

Universities are struggling to remain open in the face of COVID-19 infections among affiliates. There are a number of modalities to reduce the transmission of SARS-CoV-2, but it is unclear which are worthwhile investments for any given university.
Socio-demographic and Clinical Characteristics of Adults with SARS-CoV-2 Infection in Two Hospitals in Bogota, Colombia
Authors: Moscoso D Alejandro , Sanchez Alejandra , Aya Adriana , Gomez Carolina , Rodriguez Yazmin , Garzon Javier , Lobelo Felipe
Published: August 2020

This study is a retrospective cohort of 122 adult patients with SARS-CoV-2 diagnosed and managed at two medium-sized, tertiary private Hospitals. The analysis includes demographic and socio-economic information, symptoms, comorbidities, laboratory test results, therapeutic management, clinical outcomes and complications.