bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 seroprevalence in the city of Hyderabad, India in early 2021
Authors: Laxmaiah Avula , Rao Nalam Madhusudhan , Arlappa N. , Babu Jagjeevan , Kumar P. Uday , Singh Priya , Sharma Deepak , Mahesh Anumalla V. , Santhosh Kumar T. , Sabarinathan R. , Santhos Kumar M. , Ananthan R. , Blessy P.P.S. , Kumar D. Chandra , Devaraj P. , Devendra S. , Mahesh Kumar M. , Meshram Indrapal I. , Naveen Kumar B. , Sharma Paras , Raghavendra P. , Raghu P. , Rajender Rao K. , Ravindranadh P. , Santosh Kumar B. , Sarika  , Srinivasa Rao J. , Surekha M.V. , Sylvia F. , Kumar Deepak , Subba Rao G. , Tallapaka Karthik Bharadwaj , Sowpati Divya Tej , Srivastava Surabhi , Murekhar Manoj , Hemalatha Rajkumar , Mishra Rakesh K
Published: July 2021

Background

COVID-19 emerged as a global pandemic in 2020, rapidly spreading to most parts of the world. The proportion of infected individuals in a population can be reliably estimated via sero-surveillance, making it a valuable tool for planning control measures. We conducted a serosurvey study to investigate SARS-CoV-2 seroprevalence in the urban population of Hyderabad at the end of the first wave of infections.

Methods

The cross-sectional survey conducted in January 2021 included males and females aged 10 years and above, selected by multi-stage random sampling. 9363 samples were collected from 30 wards distributed over 6 zones of Hyderabad and tested for antibodies against SARS-CoV-2 nucleocapsid antigen.

Results

Overall seropositivity was 54.2%, ranging from 50-60% in most wards. Highest exposure appeared to be among 30-39y and 50-59y olds, with women showing greater seropositivity. Seropositivity increased with family size, with only marginal differences among people with varying levels of education. Seroprevalence was significantly lower among smokers. Only 11% of the survey subjects reported any COVID-19 symptoms, while 17% had appeared for Covid testing.

Conclusion

Over half the city’s population was infected within a year of onset of the pandemic. However, ∼46% people were still susceptible, contributing to subsequent waves of infection.

Highlights

⍰

National level serosurveys under-estimate localised prevalence in dense urban areas

⍰

SARS-CoV-2 seroprevalence in Hyderabad city was 54.2% after the first wave

⍰

A large proportion of the population remains at risk over a year into the pandemic
Evaluation of the antibody response and adverse reactions of the BNT162b2 vaccine of participants with prior COVID-19 infection in Japan
Authors: Mitsunaga Toshiya , Ohtaki Yuhei , Seki Yutaka , Yoshioka Masakata , Mori Hiroshi , Suzuka Midori , Mashiko Syunsuke , Takeda Satoshi , Mashiko Kunihiro
Published: July 2021

Introduction

Vaccination programs are important to preventing COVID-19 infection. BNT162b2 is new type of vaccine, and previous studies have shown that the antibody response was significantly elevated in patients with prior COVID-19 infection after the first vaccination. However, no study has evaluated the efficacy of the vaccination or the adverse reactions of people with prior COVID-19 infection in Japan. The aim of this study is to evaluate the antibody titer and adverse reactions of BNT162b2 vaccine among participants with prior COVID-19 infection in Japan.

Methods

The data for this study was collected between April 15, 2021, and June 9, 2021. All of the hospital staff who received the BNT162b2 vaccine were included in this study and were sorted into either the prior infection group or the control group. We collected the data of adverse reactions through self-reporting and calculated the anti-SARS-CoV-2 spike-specific antibody titer for all participants.

Results

The antibody titer of the prior-infection group in first antibody test was significantly higher than that of the control group in the second antibody test. There was no significant difference in adverse reactions between the prior infection group receiving its first vaccination and the control group receiving its second vaccination.

Conclusion

Our study shows that the antibody response following the first vaccination in the prior COVID-19 infection group was found to be comparable to that of the second vaccination in the control group; however, the evaluation of adverse reactions was inadequate and further, large-scale studies are needed.
Identification of Parkinson PACE subtypes and repurposing treatments through integrative analyses of multimodal clinical progression, neuroimaging, genetic, and transcriptomic data
Authors: Su Chang , Hou Yu , Xu Jielin , Xu Zhenxing , Xu Jie , Brendel Matthew , Maasch Jacqueline R. M. A. , Bai Zilong , Zhang Haotan , Zhu Yingying , Cincotta Molly C. , Shi Xinghua , Henchcliffe Claire , Leverenz James B. , Cummings Jeffrey , Okun Michael S. , Bian Jiang , Cheng Feixiong , Wang Fei
Published: July 2021

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by significant clinical and progression heterogeneity resulting from complex pathophysiological mechanisms. This study aimed at addressing heterogeneity of PD through the integrative analysis of a broad spectrum of data sources. We analyzed clinical progression data spanning over 5 years from individuals withde novoPD, using machine learning and deep learning, to characterize individuals’ phenotypic progression trajectories for subtyping. We discovered three pace subtypes of PD which exhibited distinct progression patterns and were stable over time: the Inching Pace subtype (PD-I) with mild baseline severity and mild progression speed; the Moderate Pace subtype (PD-M) with mild baseline severity but advancing at a moderate progression rate; and the Rapid Pace subtype (PD-R) with the most rapid symptom progression rate. We found that cerebrospinal fluid P-tau/α-synuclein ratio and atrophy in certain brain regions measured by neuroimaging might be indicative markers of these subtypes. Furthermore, through genetic and transcriptomic data analyses enhanced by network medicine approaches, we detected molecular modules associated with each subtype. For instance, the PD-R-specific module suggestedSTAT3,FYN,BECN1,APOA1,NEDD4, andGATA2as potential driver genes of PD-R. Pathway analysis suggested that neuroinflammation, oxidative stress, metabolism, AD, PI3K/AKT, and angiogenesis pathways may drive rapid PD progression (i.e., PD-R). Moreover, we identified candidate repurposable drugs via targeting these subtype-specific molecular modules and estimated their treatment effects using two large-scale real-world patient databases. The real-world evidence we gained revealed metformin’s potential in ameliorating PD progression. In conclusion, our findings illuminated distinct PD pace subtypes with differing progression patterns, uncovered potential biological underpinnings driving different subtypes, and predicted repurposable drug candidates. This work may help better understand clinical and pathophysiological complexity of PD progression and accelerate precision medicine.
Comparative immunogenicity and effectiveness of mRNA-1273, BNT162b2 and Ad26.COV2.S COVID-19 vaccines
Authors: Naranbhai Vivek , Garcia-Beltran Wilfredo F. , Chang Christina C. , Mairena Cristhian Berrios , Thierauf Julia C. , Kirkpatrick Grace , Onozato Maristela L. , Cheng Ju , St. Denis Kerri J. , Lam Evan C. , Kaseke Clarety , Tano-Menka Rhoda , Yang Diane , Pavlovic Maia , Yang Wendy , Kui Alexander , Miller Tyler E. , Astudillo Michael G. , Cahill Jennifer E. , Dighe Anand S. , Gregory David J. , Poznansky Mark C. , Gaiha Gaurav D. , Balazs Alejandro B. , Iafrate A. John
Published: July 2021

Background

Understanding immunogenicity and effectiveness of SARS-CoV-2 vaccines is critical to guide rational use.

Methods

We compared the immunogenicity of mRNA-1273, BNT-162b2 or Ad26.COV2.S in ambulatory adults in Massachusetts, USA. To correlate immunogenicity with effectiveness of the three vaccines, we performed an inverse-variance meta-analysis of population level effectiveness from public health reports in >40 million individuals.

Results

A single dose of either mRNA vaccine yielded comparable antibody and neutralization titers to convalescent individuals. Ad26.COV2.S yielded lower antibody concentrations and frequently negative neutralization titers. Bulk and cytotoxic T-cell responses were higher in mRNA1273 and BNT162b2 than Ad26.COV2.S recipients, and <50% of vaccinees demonstrate CD8+ T-cell responses to spike peptides. Antibody concentrations and neutralization titers increased comparably after the first dose of either vaccine, and further in recipients of a second dose. Prior infection was associated with high antibody concentrations and neutralization even after a single dose and regardless of vaccine. Neutralization of beta, gamma and delta strains were poorer regardless of vaccine. Relative to mRNA1273, the effectiveness of BNT162b2 was lower against infection and hospitalization; and Ad26COV2.S was lower against infection, hospitalization and death.

Conclusions

Variation in the immunogenicity correlates with variable effectiveness of the three FDA EUA vaccines deployed in the USA.
Association of long-term body weight variability with dementia: a prospective study
Authors: Chen Hui , Zhou Tianjing , Guo Jie , Ji John S. , Huang Liyan , Xu Weili , Zuo Guangmin , Lv Xiaozhen , Zheng Yan , Hofman Albert , Ma Yuan , Yuan Changzheng
Published: July 2021

Introduction

We aimed to investigate whether long-term body weight variability (BWV) is associated with late-life dementia and to further assess their potential temporal relationships.

Methods

In 5,547 participants in Health and Retirement Study (HRS), a population-based prospective cohort, we quantified BWV as coefficient of variation using self-reported body weight from 1992 to 2008 and followed their dementia status from 2008 to 2016.

Results

A total of 427 incident dementia cases were identified. Larger long-term BWV was significantly associated with higher risk of dementia (HR comparing extreme quartiles: 2.01, 95% CI: 1.48-2.72; HR of each SD increment: 1.21, 95% CI,1.10-1.32; p-trend<0.001). This significant association was even observed for BWV estimated approximately 15 years preceding dementia diagnosis (HR of each SD increment: 1.13, 95% CI: 1.03-1.23) and was more pronounced for that closer to diagnosis.

Discussion

Our findings suggested that large BWV could be a novel risk factor for dementia.
Low cost, injection molded, nasopharyngeal swabs for addressing global diagnostic supply shortages
Authors: Martinez Manuel Ramses , Mendoza Rachelle , Perry David , Gabutan Elmer , Fyke William , Faber Eve , Saggi Subodh J , Tam Jenny , Chico-Calero Isabel , Centner Heather , Engelthaler David M. , Goetz Laura H. , McDaniel Timothy K. , Murakami Noriyuki , Libien Jenny , Ingber Donald E. , Novak Richard
Published: July 2021

The SARS-CoV-2 pandemic revealed the fragility of global supply chains, resulting in shortages of essential clinical supplies for the detection and treatment of COVID-19, including nasopharyngeal swabs (NP) commonly used to collect clinical samples for respiratory disease diagnostics. Groups around the world led a response to find alternatives to these shortages. Here, we describe the development of a single-component nasopharyngeal swab (GrooveSwab) composed of medical grade polypropylene that can be mass manufactured using conventional injection molding. The design inspired by cat tongue papillae consists of a non-absorbent stacked ring structure that allows for efficient and comfortable collection of viscous mucus samples and faster release into collection medium compared to traditional absorbent swabs. GroveSwabs were evaluated in 2 clinical studies in the US and Peru and demonstrated 90% or better concordance with commercial swabs. The simplified NP swab offers a reliable, lower cost, and more manufacturable alternative to absorbent swabs to avoid future shortages.
Potential impacts of Washington State’s wildfire worker protection rule on construction workers
Authors: Zuidema Christopher , Austin Elena , Cohen Martin A. , Kasner Edward , Liu Lilian , Isaksen Tania Busch , Lin Ken-Yu , Spector June , Seto Edmund
Published: July 2021

Driven by climate change, wildfires are increasing in frequency, duration, and intensity across the Western United States. Outdoor workers are being exposed to increasing wildfire-related particulate matter and smoke. Recognizing this emerging risk, Washington adopted an emergency rule and is presently engaged in creating a permanent rule to protect outdoor workers from wildfire smoke exposure. While there are growing bodies of literature on the exposure to and health effects of wildfire smoke in the general public and wildland firefighters, there is a gap in knowledge about wildfire smoke exposure among outdoor workers generally, and construction workers specifically, a large category of outdoor workers in Washington totaling 200,000 people. In this study, several data sources were linked including state-collected employment data and national ambient air quality data to gain insight into the risk of PM2.5exposure among construction workers and evaluate the impacts of different air quality thresholds that would have triggered a new Washington emergency wildfire smoke rule aimed at protecting workers from high PM2.5exposure. Results indicate the number of poor air quality days has increased in August and September in recent years. Over the last decade these months with the greatest potential for particulate matter exposure coincided with an annual peak in construction employment that was typically 9.4 to 42.7% larger across Washington counties (one county was 75.8%). Lastly, the “encouraged” threshold of the Washington emergency rule (20.5 μg/m3) would have resulted in 5.5 times more days subject to the wildfire rule on average across all Washington counties compared to its “required” threshold (55.5 μg/m3), and in 2020 the rule could have created demand for 1.35 million N-95 filtering facepiece respirators among construction workers. These results have important implications for both employers and policy makers as rules are developed. The potential policy implications of wildfire smoke exposure, exposure control strategies, and data gaps that would improve understanding of construction worker exposure to wildfire smoke are also discussed.
Increased transmissibility of emerging SARS-CoV-2 variants is driven either by viral load or probability of infection rather than environmental stability
Authors: Arav Yehuda , Fattal Eyal , Klausner Ziv
Published: July 2021

Understanding the factors that increase the transmissibility of the recently emerging variants of SARS-CoV-2 (such as the Alpha, Epsilon, and Delta variants) can aid in mitigating their spread. The enhanced transmissibility could be attributed to one or more factors: higher stability on surfaces or within droplet nuclei suspended in air, increased maximal viral load or higher probability of infection. The relative importance of these factors on the transmission was examined using a validated stochastic-jump-continuous hybrid model. The transmissibility was quantified in terms of the household secondary attack rate (hSAR) which is the probability of transmission from an infected individual to a susceptible one in a household. We find that an increase in either the maximal viral load or the probability of infection is consistent with the observed hSAR of the variants. Specifically, in order to reach the relative increase in the hSAR of 40%, 55%, and 87% reported for the Epsilon, Alpha, and Delta variants (respectively), the maximal viral load should increase by 56%, 78%, and 125%, respectively. Alternatively, the probability of infection should increase by 34%, 53%, and 193%, respectively. Contrary to these results, even a dramatic increase in environmental stability increases hSAR by no more than 10%.
SARS-CoV-2 Genomic Surveillance Reveals Little Spread Between a Large University Campus and the Surrounding Community
Authors: Valesano Andrew L. , Fitzsimmons William J. , Blair Christopher N. , Woods Robert J. , Gilbert Julie , Rudnik Dawn , Mortenson Lindsey , Friedrich Thomas C. , O’Connor David H. , Petrie Joshua G. , Martin Emily T. , Lauring Adam S.
Published: July 2021

COVID-19 has had high incidence at institutions of higher education (IHE) in the United States, but the transmission dynamics in these settings are not well understood. It remains unclear to what extent IHE-associated outbreaks have contributed to transmission in nearby communities. We implemented high-density prospective genomic surveillance to investigate these dynamics at the University of Michigan-Ann Arbor and the surrounding community during the Fall 2020 semester (August 16th –November 24th). We sequenced complete SARS-CoV-2 genomes from 1659 individuals, including 468 students, representing 20% of cases in students and 25% of total confirmed cases in Washtenaw County over the study interval. Phylogenetic analysis identified over 200 introductions into the student population, most of which were not related to other student cases. There were two prolonged transmission clusters among students that spanned across multiple on-campus residences. However, there were very few genetic descendants of student clusters among non-students during a subsequent November wave of infections in the community. We conclude that outbreaks at the University of Michigan did not significantly contribute to the rise in Washtenaw County COVID-19 incidence during November 2020. These results provide valuable insights into the distinct transmission dynamics of SARS-CoV-2 among IHE populations and surrounding communities.
Association between reactogenicity and SARS-CoV-2 antibodies after the second dose of the BNT162b2 COVID-19 vaccine
Authors: Yamamoto Shohei , Fukunaga Ami , Tanaka Akihito , Takeuchi Junko S. , Inoue Yosuke , Kimura Moto , Maeda Kenji , Ueda Gohzoh , Mizoue Tetsuya , Ujiie Mugen , Sugiura Wataru , Ohmagari Norio
Published: July 2021

High vaccine reactogenicities may reflect stronger immune responses, but the epidemiological evidence for coronavirus disease 2019 (COVID-19) vaccines is sparse and inconsistent. We observed that a fever of ≥38□ after two doses of the BNT162b2 vaccine was associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG titers.
Global predictions of short- to medium-term COVID-19 transmission trends : a retrospective assessment
Authors: Bhatia Sangeeta , Parag Kris V , Wardle Jack , Imai Natsuko , Van Elsland Sabine L , Lassmann Britta , Cuomo-Dannenburg Gina , Jauneikaite Elita , Unwin H. Juliette T. , Riley Steven , Ferguson Neil , Donnelly Christl A , Cori Anne , Nouvellet Pierre
Published: July 2021

Background

As of July 2021, more than 180,000,000 cases of COVID-19 have been reported across the world, with more than 4 million deaths. Mathematical modelling and forecasting efforts have been widely used to inform policy-making and to create situational awareness.

Methods and Findings

From 8th March to 29th November 2020, we produced weekly estimates of SARS-CoV-2 transmissibility and forecasts of deaths due to COVID-19 for countries with evidence of sustained transmission. The estimates and forecasts were based on an ensemble model comprising of three models that were calibrated using only the reported number of COVID-19 cases and deaths in each country. We also developed a novel heuristic to combine weekly estimates of transmissibility and potential changes in population immunity due to infection to produce forecasts over a 4-week horizon. We evaluated the robustness of the forecasts using relative error, coverage probability, and comparisons with null models.

Conclusions

During the 39-week period covered by this study, we produced short- and medium-term forecasts for 81 countries. Both the short- and medium-term forecasts captured well the epidemic trajectory across different waves of COVID-19 infections with small relative errors over the forecast horizon. The model was well calibrated with 56.3% and 45.6% of the observations lying in the 50% Credible Interval in 1-week and 4-week ahead forecasts respectively. We could accurately characterise the overall phase of the epidemic up to 4-weeks ahead in 84.9% of country-days. The medium-term forecasts can be used in conjunction with the short-term forecasts of COVID-19 mortality as a useful planning tool as countries continue to relax stringent public health measures that were implemented to contain the pandemic.
Vaccine Approvals and the Role of the FDA Vaccine Advisory Committee, 2000-2019
Authors: Kanter Genevieve P. , Vallurupalli Neel , Xu Yao , Gupta Ravi
Published: July 2021

Background

The US Food and Drug Administration (FDA) plays a critical role in bolstering public confidence in vaccines and the vaccine review process. An important tool for enhancing transparency and public trust is the FDA’s Vaccine and Biological Related Products Advisory Committee (VRBPAC), a group of external experts that advises on scientific issues related to the licensure of vaccines.

Objective

To analyze key features of VRBPAC meetings convened over 20 years; estimate the probability of advisory committee review of newly approved vaccines, focusing on vaccines targeting emerging diseases; and examine the speed of and variance in approval times as a function of VRBPAC review.

Methods

Cross-sectional study of VRBPAC meetings convened and new vaccine licensure applications approved between January 1, 2000, and December 31, 2019. We analyzed the frequency of VRBPAC meetings and sessions; the percentage of newly licensed vaccines reviewed by VRBPAC; and the number of days between the submission of the licensure application and the date of FDA approval.

Results

Between 2000 and 2019, VRBPAC convened for a mean of 4.1 sessions per year. One-quarter of sessions was devoted to the review of specific vaccine products. During the same period, 44 new vaccine licensures were approved, 20% of which were for vaccines targeting emerging diseases. Almost half (48%) of successful new vaccine applications were reviewed by VRBPAC (n=21), a rate lower than for therapeutic applications. Among new applications targeting emerging diseases, 29% of non-influenza vaccines were reviewed by VRBPAC. There was no difference in the median time to approval as a function of VRBPAC review (364 days with VRBAC review vs. 365 days with no review, p=0.870).

Conclusion

The FDA has convened VRBPAC for reviews of about half of its vaccine products, less frequently for vaccines against non-influenza emerging diseases. There is considerable scope for the FDA to increase VRBPAC engagement in the vaccine review process.
Prevalence of SARS CoV-2 infection among Health Care Workers of a hybrid tertiary COVID 19 hospital in Kerala
Authors: Jessy S J , Beegum M Shamha , Genga S , Bindu G , Chintha S , Sasidharan Sukshma , Tonio Ansu , Aravind R
Published: July 2021

Back ground and objectives

This study was undertaken to estimate the prevalence of SARS-CoV-2 infection among Health care workers [HCWs] of a hybrid COVID treatment hospital in Kerala.

Methods

The study was conducted during 3rd week of January 2021. Among 3550 HCWs, 979 subjects were selected by stratified random sampling and grouped into high risk and low risk category based on job setting. Demographic details and clinical information regarding previous history of COVID 19 were collected at the time of SARS-CoV-2 IgG testing.

Results

From 979 subjects, the data with respect to 940 health care workers were analysed. SARS-CoV-2 IgG was detected in 19.1% of HCWs. Seroprevalence among high risk group was 20.3% and that in low risk group was 7.4% [p=0.005]. In high-risk group, seropositivity was noted in 30.54 % of nurses, 19% hospital attenders, 18.9% resident doctors and 6.4% consultant doctors. In those with past history of SARS-CoV-2 infection, seropositivity was 75.4%. In those who were COVID positive during July2020, 33.3% were still IgG reactive.

Interpretation and conclusion

The study reported 19.1% SARS CoV-2 IgG reactivity among health care workers in our hospital. Seropositivity was significantly higher in high risk group compared to low risk group. Antibody decay kinetics in our study is comparable to that in published literature. Infection control challenges in hybrid hospitals account for higher seropositivity in this study compared to overall seroprevalence among HCWs in Kerala.
Delta variants of SARS-CoV-2 cause significantly increased vaccine breakthrough COVID-19 cases in Houston, Texas
Authors: Christensen Paul A. , Olsen Randall J. , Long S. Wesley , Subedi Sishir , Davis James J. , Hodjat Parsa , Walley Debbie R. , Kinskey Jacob C. , Saavedra Matthew Ojeda , Pruitt Layne , Reppond Kristina , Shyer Madison N. , Cambric Jessica , Gadd Ryan , Thakur Rashi M. , Batajoo Akanksha , Mangham Regan , Pena Sindy , Trinh Trina , Yerramilli Prasanti , Nguyen Marcus , Olson Robert , Snehal Richard , Gollihar Jimmy , Musser James M.
Published: July 2021

Genetic variants of SARS-CoV-2 have repeatedly altered the course of the COVID-19 pandemic. Delta variants of concern are now the focus of intense international attention because they are causing widespread COVID-19 disease globally and are associated with vaccine breakthrough cases. We sequenced the genomes of 16,965 SARS-CoV-2 from samples acquired March 15, 2021 through September 20, 2021 in the Houston Methodist hospital system. This sample represents 91% of all Methodist system COVID-19 patients during the study period. Delta variants increased rapidly from late April onward to cause 99.9% of all COVID-19 cases and spread throughout the Houston metroplex. Compared to all other variants combined, Delta caused a significantly higher rate of vaccine breakthrough cases (23.7% for Delta compared to 6.6% for all other variants combined). Importantly, significantly fewer fully vaccinated individuals required hospitalization. Individuals with vaccine breakthrough cases caused by Delta had a low median PCR cycle threshold (Ct) value (a proxy for high virus load). This value was closely similar to the median Ct value for unvaccinated patients with COVID-19 caused by Delta variants, suggesting that fully vaccinated individuals can transmit SARS-CoV-2 to others. Patients infected with Alpha and Delta variants had several significant differences. Our integrated analysis emphasizes that vaccines used in the United States are highly effective in decreasing severe COVID-19 disease, hospitalizations, and deaths.
Why is patient safety a challenge? Insights from the Professionalism Opinions of Medical Students’ (PoMS) Research
Authors: McGurgan P , Calvert K. , Narula K. , Nathan E. , Celenza A. , Jorm C.
Published: July 2021

Introduction

Despite increased emphasis on education and training for patient safety in medical schools, there is little known about factors influencing decision making regarding patient safety behaviours. This study examined the nature and magnitude of factors which may influence opinions around patient safety related behaviours as a means of providing insights into how Australian doctors and medical students view these issues relative to members of the public.

Methods

A national, multicentre, prospective, on-line cross sectional survey was conducted using responses to hypothetical clinical scenarios. Three cohorts were surveyed - Australian enrolled medical students, medical doctors and members of the public.

Participant responses were compared for the different contextual variables within the scenarios and the participants’ demographic characteristics – student, doctor, member of the public, gender and age (if public or doctors)/ seniority in the course (if a medical student).

Results

In total there were 2602 medical student participants, 809 doctors and 503 members of the Australian public. Medical doctors were more likely than other cohorts to have statistically significant differences in how they viewed the acceptability of patient safety related behaviours; doctors were more tolerant of medical students not reporting concerning behaviours. Medical students’ opinions frequently demonstrated a ‘transition effect’, bridging between the doctors and publics’ attitudes, consistent with professional identity formation.

Conclusions

Opinions on the acceptability of medical students’ patient safety related behaviours were influenced by the demographics of the cohort and the contextual complexity of the scenario. Although the survey used hypothetical scenarios, doctors and medical students’ opinions appear to be influenced by cognitive dissonances, biases and heuristics which may negatively affect patient safety.

‘Opinion is the medium between knowledge and ignorance’ Plato
Increase in ventilatory ratio indicates progressive alveolar damage and suggests poor prognosis in severe COVID-19: A single-center retrospective observational study
Authors: Kaku Natsuko , Nakagama Yu , Shirano Michinori , Shinomiya Sari , Shimazu Kazuhiro , Yamazaki Katsuaki , Maehata Yoshito , Morita Ryo , Nitahara Yuko , Yamamoto Hiromasa , Mizobata Yasumitsu , Kido Yasutoshi
Published: July 2021

Background

The symptoms of severe COVID-19 are complex and wide-ranging even in intensive care unit (ICU) patients, who may successfully discontinue respiratory support in a short period or conversely require prolonged respiratory support. Damage in the lungs of COVID-19 patients is characterized pathologically as diffuse alveolar damage, the degree of which correlates with the severity of the disease. We hypothesized that the ventilatory ratio (VR), a surrogate parameter for the dead space fraction, might stratify the severity of COVID-19 and predict the successful discontinuation of respiratory support.

Methods

Forty COVID-19 patients in our ICU were enrolled in this study. Respiratory variables were collected from 2 hours (day 0) after the initiation of respiratory support. We monitored the longitudinal values of VR and other respiratory parameters for 28 days. Patients successfully discontinued from respiratory support by day 28 of ICU stay were defined as the successfully discontinued group, while those who died or failed to discontinue were defined as the failed to discontinue group. VR and other respiratory parameters were compared between these groups.

Results

Except for advanced age, prolonged ventilation period, and higher mortality in the failed to discontinue group, there were no significant differences between the groups in terms of any other background or respiratory parameter at 2 hours (day 0) after initiation of respiratory support. Longitudinal VR monitoring revealed significantly higher VR values in the failed to discontinue group than the successfully discontinued group on day 4 of respiratory support. Upon predicting the failure to discontinue respiratory support, the area under the receiver operating characteristic curve of VR values on day 4 of respiratory support was 0.748. A threshold of 1.56 achieved the highest predictive performance with a sensitivity of 0.667 and a specificity of 0.762. This threshold enabled the prediction of the successfully discontinued outcome at 0.810 of the negative predictive value.

Conclusions

Elevated VR values on day 4 of respiratory support were predictive of successful discontinuation of respiratory support in patients with severe COVID-19. Longitudinal VR values after initiation of respiratory support can be used as a practical index to stratify severe COVID-19.
Longitudinal analysis of antibody responses to the Pfizer BNT162b2 vaccine in Patients Undergoing Maintenance Hemodialysis
Authors: Weigert André , Bergman Marie-Louise , Gonçalves Lígia , Godinho Iolanda , Duarte Nádia , Abrantes Rita , Borges Patrícia , Brennand Ana , Malheiro Vanessa , Matoso Paula , Akpogheneta Onome , Kosack Lindsay , Cruz Pedro , Nogueira Estela , Pereira Magda , Ferreira Ana , Marques Marco , Nunes Telmo , Viana João , Demengeot Jocelyne , Penha-Gonçalves Carlos
Published: July 2021

Background

Hemodialyzed patients are at higher risk for COVID-19 and were prioritized in the Portuguese vaccination campaign

Methods

We performed a prospective, longitudinal, cohort analysis of 143 patients on hemodialysis and 143 age-matched controls along BTN162b2 vaccination. ELISA quantified anti-full-length Spike IgG, IgM and IgA levels prior to the first vaccine dose (t0); 3 weeks later (second dose, t1); and 3 weeks later (t2); 127 patients were re-evaluated140 (t3) and 180 days (t4) after the first dose.

Results

Seroconversion at t1 was remarkably low in patients, with positivity for anti-spike IgG, IgM and IgA antibodies of 29.4%, 12% and 41%, respectively, increasing to 90.9% (IgG) and 83.9% (IgA) in t2, (IgM remained unchanged). Below 70 years of age anti-spike IgG levels at t1 were significantly lower compared to age-matched controls and showed a profile similar to older individuals. Immunosuppression was associated with lower antibody responses (p=0.005 at t1; p=0.008 at t2). Previous unresponsiveness to hepatitis B vaccination (75/129, 58% of patients negative for anti-HBs antibodies) did not correlate with humoral unresponsiveness to BTN162b2. Anti-spike IgG, IgM and IgA positivity and antibody levels significantly decay at t3, with IgG levels showing further waning at t4.

Conclusions

The large majority of hemodialyzed patients showed IgG seroconversion upon BNT162b2 mRNA vaccination, albeit a sizable proportion of patients presented poor responses. Follow-up of antibody responses 180 days post vaccination unveiled significant decay of anti-spike antibodies and warrant close monitoring of COVID-19 infection and further studies on reinforced vaccination schedules in patients undergoing maintenance hemodialysis.
Monday effect on confirmed cases of COVID-19 in Japan*
Authors: Nakagawa Kuninori , Kanatani Taro
Published: July 2021

We examined the phenomenon of fewer new confirmed cases of COVID-19 on Mondays in Japan, which we refer to as the Monday effect, and reveal the details of this effect. Specifically, we estimated the difference between the number of new positive cases that decreased over the weekend and the number of new confirmed cases that decreased at the beginning of the week. In Japan, prefectures aggregate and announce the number of confirmed daily cases. This analysis allows us to examine whether there is a Monday effect in each prefecture. We show that the Monday effect is due to the decreased number of inspections on the weekend appearing at the beginning of the week due to a time lag. Our results indicate that the administrative system causes delays in some prefectures, and that some prefectures are less likely to conduct screenings on holidays. Our results also suggest that delays generally occur in prefectures with a population of over 2 million. Congestion, Reporting delay, Public health, COVID-19
Probing the association between resting state brain network dynamics and psychological resilience
Authors: Kraft Dominik , Fiebach Christian J.
Published: July 2021

This study aimed at replicating a previously reported negative correlation between node flexibility and psychological resilience, i.e., the ability to retain mental health in the face of stress and adversity. To this end, we used multiband resting-state BOLD fMRI (TR = .675 sec) from 52 participants who had filled out three psychological questionnaires assessing resilience. Time-resolved functional connectivity was calculated by performing a sliding window approach on averaged time series parcellated according to different established atlases. Multilayer modularity detection was performed to track network reconfigurations over time and node flexibility was calculated as the number of times a node changes community assignment. In addition, node promiscuity (the fraction of communities a node participates in) and node degree (as proxy for time-varying connectivity) were calculated to extend previous work. We found no substantial correlations between resilience and node flexibility. We observed a small number of correlations between the two other brain measures and resilience scores, that were however very inconsistently distributed across brain measures, differences in temporal sampling, and parcellation schemes. This heterogeneity calls into question the existence of previously postulated associations between resilience and brain network flexibility and highlights how results may be influenced by specific analysis choices.

Author Summary

We tested the replicability and generalizability of a previously proposed negative association between dynamic brain network reconfigurations derived from multilayer modularity detection (node flexibility) and psychological resilience. Using multiband resting-state BOLD fMRI data and exploring several parcellation schemes, sliding window approaches, and temporal resolutions of the data, we could not replicate previously reported findings regarding the association between node flexibility and resilience. By extending this work to other measures of brain dynamics (node promiscuity, degree) we observe a rather inconsistent pattern of correlations with resilience, that strongly varies across analysis choices. We conclude that further research is needed to understand the network neuroscience basis of mental health and discuss several reasons that may account for the variability in results.
A machine learning model for screening of body fluid cytology smears
Authors: Sanyal Parikshit , Paul Sayak , Rana Vandana , Kulhari Kanchan
Published: July 2021

Introduction

Body fluid cytology is one of the commonest investigations performed in indoor patients, both for diagnosis of suspected carcinoma as well as staging of known carcinoma. Carcinoma is diagnosed in body fluids by the pathologist through microscopic examination and searching for malignant epithelial cell clusters. The process of screening body fluid smears is a time consuming and error prone process.

Aim

We have attempted to construct a machine learning model which can screen body fluid cytology smears for malignant cells.

Materials and methods

MGG stained Ascitic / pleural fluid cytology smears were included from 21 cases (14 malignant, 07 benign) in this study. A total of 693 microphotographs were taken at 40x magnification at the same illumination and after correction of white balance. A Magnus Microphotography system was used for photography. The images were split into the training set (195 images), test set (120 images) and validation set (378 images).

A machine learning model, a convolutional neural network, was developed in the Python programming language using the Keras deep learning library. The model was trained with the images of the training set. After completion of training, the model was evaluated on the test set of images.

Results

Evaluation of the model on the test set produced a sensitivity of 97.87%, specificity 85.26%, PPV 95.18%, NPV 93.10% In 06 images, the model has failed to detect singly scattered malignant cells/ clusters. 14 (3.7%) false positives was reported by the model.

The machine learning model shows potential utility as a screening tool. However, it needs improvement in detecting singly scattered malignant cells and filtering inflammatory infiltrate.
High potency of sequential therapy with only β-lactam antibiotics
Authors: Batra Aditi , Roemhild Roderich , Rousseau Emilie , Franzenburg Soeren , Niemann Stefan , Schulenburg Hinrich
Published: July 2021

Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution- informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross- resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs.
Rewiring phospholipid biosynthesis reveals robustness in membrane homeostasis and uncovers lipid regulatory players
Authors: Peter Arun T. John , van Schie Sabine N. S. , Cheung Ngaam J. , Michel Agnès H. , Peter Matthias , Kornmann Benoît
Published: July 2021

Intracellular transport of lipids by Lipid Transport Proteins (LTPs) is thought to work alongside vesicular transport to shuttle lipids from their place of synthesis to their destinations. Whereas many LTPs have been identified, it is largely unknown which routes and which LTPs a given lipid utilizes to navigate the multiple membranes of eukaryotic cells. The major and essential phospholipids, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) can be produced by multiple pathways and, in the case of PE, also at multiple locations. Here, we present an approach in which we simplify and rewire yeast phospholipid synthesis by redirecting PE and PC synthesis reactions to distinct subcellular locations using chimeric enzymes fused to specific organelle targeting motifs. In rewired conditions, viability is expected to depend on homeostatic adaptation to the ensuing lipostatic perturbations and on efficient interorganelle lipid transport. We therefore performed genetic screens to identify factors involved in both of these processes. Among the candidates identified, we find genes linked to transcriptional regulation of lipid homeostasis, lipid metabolism and transport. In particular, we identify a requirement for Csf1 –an uncharacterized protein harboring a Chorein-N lipid transport domain- for survival under certain rewired conditions as well as lipidomic adaptation to cold, implicating Csf1 in interorganelle lipid transport and homeostatic adaptation.
How sequence context-dependent mutability drives mutation rate variation in the genome
Authors: Oman Madeleine , Alam Aqsa , Ness Rob W.
Published: July 2021

The rate of mutations varies >100-fold across the genome, altering the rate of evolution, and susceptibility to genetic diseases. The strongest predictor of mutation rate is the sequence itself, varying 75-fold between trinucleotides. The fact that DNA sequence drives its own mutation rate raises a simple but important prediction; highly mutable sequences will mutate more frequently and eliminate themselves in favour of sequences with lower mutability, leading to a lower equilibrium mutation rate. However, purifying selection constrains changes in mutable sequences, causing higher rates of mutation. We conduct a simulation using real human mutation data to test if (1) DNA evolves to a low equilibrium mutation rate and (2) purifying selection causes a higher equilibrium mutation rate in the genome’s most important regions. We explore how this simple process affects sequence evolution in the genome, and discuss the implications for modelling evolution and susceptibility to DNA damage.
An Orally Available Cathepsin L Inhibitor Protects Lungs Against SARS-CoV-2-Induced Diffuse Alveolar Damage in African Green Monkeys
Authors: Frueh Felix W. , Maneval Daniel C. , Bohm Rudolf P. , Dufour Jason P. , Blair Robert V. , Powell Kathy , Aye Pyone P. , Golden Nadia A. , Roy Chad J , Spencer Sky , Russsell-Lodrigue Kasi , Plante Kenneth S. , Plante Jessica A. , McKerrow James , Rappaport Jay
Published: July 2021

The COVID-19 pandemic resulted from global infection by the SARS-CoV-2 coronavirus and rapidly emerged as an urgent health issue requiring effective treatments. To initiate infection, the Spike protein of SARS-CoV-2 requires proteolytic processing mediated by host proteases. Among the host proteases proposed to carry out this activation is the cysteine protease cathepsin L. Inhibiting cathepsin L has been proposed as a therapeutic strategy for treating COVID-19. SLV213 (K777) is an orally administered small molecule protease inhibitor that exhibits in vitro activity against a range of viruses, including SARS-CoV-2. To confirm efficacy in vivo, K777 was evaluated in an African green monkey (AGM) model of COVID-19. A pilot experiment was designed to test K777 in a prophylactic setting, animals were pre-treated with 100mg/kg K777 (N=4) or vehicle (N=2) before inoculation with SARS-CoV-2. Initial data demonstrated that K777 treatment reduced pulmonary pathology compared to vehicle-treated animals. A second study was designed to test activity in a therapeutic setting, with K777 treatment (33 mg/kg or 100 mg/kg) initiated 8 hours after exposure to the virus. In both experiments, animals received K777 daily via oral gavage for 7 days. Vehicle-treated animals exhibited higher lung weights, pleuritis, and diffuse alveolar damage. In contrast, lung pathology was reduced in K777-treated monkeys, and histopathological analyses confirmed the lack of diffuse alveolar damage. Antiviral effects were further demonstrated by quantitative reductions in viral load of samples collected from upper and lower airways. These preclinical data support the potential for early SLV213 treatment in COVID-19 patients to prevent severe lung pathology and disease progression.
Variation in scion water relations mediated by two newly released Geneva series rootstocks
Authors: Casagrande-Biasuz E. , Kalcsits L.A.
Published: July 2021

Dwarfing rootstocks are used to control tree vigor allowing for increased densities that increase apple production. Although there is considerable variation among rootstocks in dwarfing capacity, the mechanisms by which rootstocks affect vigor in apple scions remains unclear. Here, ‘Honeycrisp’ apple growth and water relations were compared among three rootstocks; M-9 as the industry standard and two less studied Geneva series rootstocks; G.87 and G. 814 in Washington, USA. Trees were acquired from a commercial nursery and planted in 2017. In 2018 and 2019, scion physiological, isotopic and morphological traits were measured to better understand the link between rootstock-driven vigor and physiological traits. Rootstock affected scion shoot growth (P <0.001), stomatal conductance (P< 0.01) and stem water potential (P <0.001). Rootstocks with low vegetative vigor like M.9 also had lower stomatal conductance and enriched leaf δ13C and δ18O isotope composition. Plant growth was positively correlated with stomatal conductance and stem water potential. Rootstocks also affected plant water status and net gas exchange. Here, we report an association between rootstock-induced vigor and scion physiological traits such as gas exchange, stem water potential, and leaf carbon and oxygen isotope composition. This research has implications for the understanding of the mechanisms of dwarfing by rootstocks in apple.