bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation to simultaneous warming and acidification carries a thermal tolerance cost in a marine copepod
Authors: deMayo James A. , Girod Amanda , Sasaki Matthew C. , Dam Hans G.
Published: July 2021

The ocean is undergoing warming and acidification. Thermal tolerance is affected both by evolutionary adaptation and developmental plasticity. Yet, thermal tolerance in animals adapted to simultaneous warming and acidification is unknown. We experimentally evolved the ubiquitous copepod
Acartia tonsa
to future combined ocean warming and acidification conditions (OWA approx. 22°C, 2000 µatm CO
2
) and then compared its thermal tolerance relative to ambient conditions (AM approx. 18°C, 400 µatm CO
2
). The OWA and AM treatments were reciprocally transplanted after 65 generations to assess effects of developmental conditions on thermal tolerance and potential costs of adaptation. Treatments transplanted from OWA to AM conditions were assessed at the F1 and F9 generations following transplant. Adaptation to warming and acidification, paradoxically, reduces both thermal tolerance and phenotypic plasticity. These costs of adaptation to combined warming and acidification may limit future population resilience.
Estimating the long-term repeatability of food-hoarding behaviours in an avian predator
Authors: Class Barbara , Masoero Giulia , Terraube Julien , Korpimäki Erkki
Published: July 2021

Food-hoarding behaviour is widespread in the animal kingdom and enables predictable access to food resources in unpredictable environments. Within species, consistent variation among individuals in food-hoarding behaviours may indicate the existence of individual strategies, as it likely captures intrinsic differences in how individuals cope with risks (e.g. starvation, pilferage). Using 17 years of data, we estimated the long-term repeatability of 10 food-hoarding behaviours in a population of Eurasian pygmy owls (Glaucidium passerinum), a small avian predator subject to high temporal fluctuations in its main prey abundance. We found low repeatability in the proportion of shrews and the average prey mass stored for both sexes, while females were moderately repeatable in the mass and the number of prey items stored. These two pairs of behaviours were tightly correlated among individuals and might represent two different sets of individual strategies to buffer against starvation risks.
Using prediction markets to predict the outcomes in the Defense Advanced Research Projects Agency's next-generation social science programme
Authors: Viganola Domenico , Buckles Grant , Chen Yiling , Diego-Rosell Pablo , Johannesson Magnus , Nosek Brian A. , Pfeiffer Thomas , Siegel Adam , Dreber Anna
Published: July 2021

There is evidence that prediction markets are useful tools to aggregate information on researchers' beliefs about scientific results including the outcome of replications. In this study, we use prediction markets to forecast the results of novel experimental designs that test established theories. We set up prediction markets for hypotheses tested in the Defense Advanced Research Projects Agency's (DARPA) Next Generation Social Science (NGS2) programme. Researchers were invited to bet on whether 22 hypotheses would be supported or not. We define support as a test result in the same direction as hypothesized, with a Bayes factor of at least 10 (i.e. a likelihood of the observed data being consistent with the tested hypothesis that is at least 10 times greater compared with the null hypothesis). In addition to betting on this binary outcome, we asked participants to bet on the expected effect size (in Cohen's
d
) for each hypothesis. Our goal was to recruit at least 50 participants that signed up to participate in these markets. While this was the case, only 39 participants ended up actually trading. Participants also completed a survey on both the binary result and the effect size. We find that neither prediction markets nor surveys performed well in predicting outcomes for NGS2.
Characterizing the supercomplex association of photosynthetic complexes in cyanobacteria
Authors: Zhang Zimeng , Zhao Long-Sheng , Liu Lu-Ning
Published: July 2021

The light reactions of photosynthesis occur in thylakoid membranes that are densely packed with a series of photosynthetic complexes. The lateral organization and close association of photosynthetic complexes in native thylakoid membranes are vital for efficient light harvesting and energy transduction. Recently, analysis of the interconnections between photosynthetic complexes to form supercomplexes has garnered great interest. In this work, we report a method integrating immunoprecipitation, mass spectrometry and atomic force microscopy to identify the inter-complex associations of photosynthetic complexes in thylakoid membranes from the cyanobacterium
Synechococcus elongatus
PCC 7942. We characterize the preferable associations between individual photosynthetic complexes and binding proteins involved in the complex–complex interfaces, permitting us to propose the structural models of photosynthetic complex associations that promote the formation of photosynthetic supercomplexes. We also identified other potential binding proteins with the photosynthetic complexes, suggesting the highly connecting networks associated with thylakoid membranes. This study provides mechanistic insight into the physical interconnections of photosynthetic complexes and potential partners, which are crucial for efficient energy transfer and physiological acclimatization of the photosynthetic apparatus. Advanced knowledge of the protein organization and interplay of the photosynthetic machinery will inform rational design and engineering of artificial photosynthetic systems to supercharge energy production.
The face value of feedback: facial behaviour is shaped by goals and punishments during interaction with dynamic faces
Authors: Yi Jonathan , Pärnamets Philip , Olsson Andreas
Published: July 2021

Responding appropriately to others' facial expressions is key to successful social functioning. Despite the large body of work on face perception and spontaneous responses to static faces, little is known about responses to faces in dynamic, naturalistic situations, and no study has investigated how goal directed responses to faces are influenced by learning during dyadic interactions. To experimentally model such situations, we developed a novel method based on online integration of electromyography signals from the participants’ face (corrugator supercilii and zygomaticus major) during facial expression exchange with dynamic faces displaying happy and angry facial expressions. Fifty-eight participants learned by trial-and-error to avoid receiving aversive stimulation by either reciprocate (congruently) or respond opposite (incongruently) to the expression of the target face. Our results validated our method, showing that participants learned to optimize their facial behaviour, and replicated earlier findings of faster and more accurate responses in congruent versus incongruent conditions. Moreover, participants performed better on trials when confronted with smiling, when compared with frowning, faces, suggesting it might be easier to adapt facial responses to positively associated expressions. Finally, we applied drift diffusion and reinforcement learning models to provide a mechanistic explanation for our findings which helped clarifying the underlying decision-making processes of our experimental manipulation. Our results introduce a new method to study learning and decision-making in facial expression exchange, in which there is a need to gradually adapt facial expression selection to both social and non-social reinforcements.
Green spectrofluorimetric assay of dantrolene sodium via reduction method: application to content uniformity testing
Authors: Abdalah Nora A. , Fathy Mona E. , Tolba Manar M. , El-Brashy Amina M. , Ibrahim Fawzia A.
Published: July 2021

Green analysis has turned out to be of a great value in all areas, including pharmaceutical analysis. Thus, it is extremely important to consider the environmental influence of each step in developing any analysis technique. The present work illustrates a validated, simple and green spectrofluorimetric method for the analysis of dantrolene sodium (DAN). The developed process is characterized by being of high sensitivity as well as being relatively inexpensive. The suggested technique based on the formation of a highly fluorescent product of DAN via its reduction by the aid of Zn/HCl system. The resulting fluorophore showed a powerful fluorescence at
λ
em
344 nm after excitation at
λ
ex
279 nm. Calibration graph revealed a great linear regression (
r
= 0.9998) within concentration ranging from 0.05 to 2.0 µg ml
−1
. The suggested method had very low detection and quantification limits of 0.010 and 0.031 µg ml
−1
, respectively. The applied technique was effectively used in the determination of DAN in its pharmaceutical preparations. The results were compared with those from using the official United States Pharmacopeia (USP) method and they were in a good agreement. Moreover, content uniformity testing of DAN in capsules was performed adopting the investigated technique with satisfying results. The greenness of the suggested technique was confirmed by the three standard assessment tools. Therefore, the developed technique can be used in the routine quality control analysis of DAN with minimum harmful impact on nature or individuals.
Case-control study of neuropsychiatric symptoms following COVID-19 hospitalization in 2 academic health systems
Authors: Castro Victor M. , Rosand Jonathan , Giacino Joseph T. , McCoy Thomas H. , Perlis Roy H.
Published: July 2021

Neuropsychiatric symptoms may persist following acute COVID-19 illness, but the extent to which these symptoms are specific to COVID-19 has not been established. We utilized electronic health records across 6 hospitals in Massachusetts to characterize cohorts of individuals discharged following admission for COVID-19 between March 2020 and May 2021, and compared them to individuals hospitalized for other indications during this period. Natural language processing was applied to narrative clinical notes to identify neuropsychiatric symptom domains up to 150 days following hospitalization. Among 6,619 individuals hospitalized for COVID-19 drawn from a total of 42,961 hospital discharges, the most commonly documented symptom domains between 31 and 90 days after initial positive test were fatigue (13.4%), mood and anxiety symptoms (11.2%), and impaired cognition (8.0%). In models adjusted for sociodemographic features and hospital course, none of these were significantly more common among COVID-19 patients; indeed, mood and anxiety symptoms were less frequent (adjusted OR 0.72 95% CI 0.64-0.92). Between 91 and 150 days after positivity, most commonly-detected symptoms were fatigue (10.9%), mood and anxiety symptoms (8.2%), and sleep disruption (6.8%), with impaired cognition in 5.8%. Frequency was again similar among non-COVID-19 post-hospital patients, with mood and anxiety symptoms less common (aOR 0.63, 95% CI 0.52-0.75). Neuropsychiatric symptoms were common up to 150 days after initial hospitalization, but occurred at generally similar rates among individuals hospitalized for other indications during the same period. Post-acute sequelae of COVID-19 thus may benefit from standard if less-specific treatments developed for rehabilitation after hospitalization.

Funding

R01MH120227, R01MH116270 (Perlis)
The antibody landscapes against Group 1 and 2 influenza virus hemagglutinin following AS03 and MF59 adjuvanted H5N1 vaccination
Authors: Goll Johannes B. , Jain Aarti , Jensen Travis L. , Assis Rafael , Nakajima Rie , Jasinskas Algis , Coughlan Lynda , Cherikh Sami R. , Gelber Casey E. , Huw Davies D. , Meade Philip , Stadlbauer Daniel , Strohmeier Shirin , Krammer Florian , Chen Wilbur H. , Felgner Philip L.
Published: July 2021

Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, we interrogated serum from subjects who received 2 doses of inactivated monovalent influenza A/Indonesia/05/2005 vaccine with or without AS03 or MF59 using hemagglutinin (HA) microarrays. The arrays were designed to reflect both full length and globular head HA proteins derived from 17 influenza A subtypes (H1 to H16 and H18) and influenza B strains. We observed significantly increased strain-specific and broad homo- and hetero-subtypic antibody responses with both AS03 and MF59 adjuvanted vaccination with AS03 achieving a higher titer and breadth of IgG responses relative to MF59. Adjuvanted vaccine was also associated with the elicitation of stalk directed antibody. Finally, we established good correlation of the array antibody responses to H5 antigens with standard hemagglutination inhibition and microneutralization titers.
Comparison of humoral and cellular responses in kidney transplant recipients receiving BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines
Authors: Prendecki Maria , Thomson Tina , Clarke Candice L. , Martin Paul , Gleeson Sarah , De Aguiar Rute Cardoso , Edwards Helena , Mortimer Paige , McIntyre Stacey , Lewis Shanice , Deborah Jaid , Cox Alison , Pickard Graham , Lightstone Liz , Thomas David , McAdoo Stephen P. , Kelleher Peter , Willicombe Michelle ,   in collaboration with the OCTAVE Study Consortium
Published: July 2021

Background

Attenuated immune responses to mRNA SARS-CoV-2 vaccines have been reported in solid organ transplant recipients. Most studies have assessed serological responses alone, and there is limited immunological data on vector-based vaccines in this population. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in a cohort of kidney transplant patients, assessing both serological and cellular responses.

Methods

920 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=490) or ChAdOx1 (n=430). 106 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group.

Results

Anti-S was detected in 569 (61.8%) patients. Seroconversion rates in infection-naïve patients who received BNT162b2 were higher compared with ChAdOx1, at 269/410 (65.6%) and 156/358 (43.6%) respectively, p<0.0001. Anti-S concentrations were higher following BNT162b, 58(7.1-722) BAU/ml, compared with ChAdOx1, 7.1(7.1-39) BAU/ml, p<0.0001. Calcineurin inhibitor monotherapy, vaccination occurring >1st year post-transplant and receiving BNT162b2 was associated with seroconversion.

Only 28/106 (26.4%) of patients had detectable T-cell responses. There was no difference in detection between infection-naïve patients who received BNT162b2, 7/40 (17.5%), versus ChAdOx1, 2/39 (5.1%), p=0.15. There was also no difference in patients with prior infection who received BNT162b2, 8/11 (72.7%), compared with ChAdOx1, 11/16 (68.8%), p=0.83.

Conclusions

Enhanced humoral responses were seen with BNT162b2 compared with ChAdOx1 in kidney transplant patients. T-cell responses to both vaccines were markedly attenuated. Clinical efficacy data is still required but immunogenicity data suggests weakened responses to both vaccines in transplant patients, with ChAdOx1 less immunogenic compared with BNT162b2.
Student nurses’ views on shift patterns: what do they prefer and why? Results from a Tweetchat
Authors: Dall’Ora Chiara , Sainsbury Jessica , Allen Chris
Published: July 2021

Aim

To understand student nurses’ views around shift patterns.

Design

Qualitative study

Method

We held a Tweetchat in May 2019, where we asked questions around the frequency of 12-hour shifts working on placement; schedule flexibility while on placement; which shift patterns they preferred and why. Data from the Tweetchat were analysed to identify emerging themes and inductively develop a coding frame.

Results

Seventy-three nursing students participated in the Tweetchat. The majority (68%) of respondents reported that they work 12-hour shifts on placements. We identified three main overarching themes: “Achieving a personal equilibrium”; “Meeting the needs of the care environment”, “Factors affecting negotiation capacity”. Data highlighted a conflict for most students, where they preferred 12-hour shifts because of more time off for study, paid work, and leisure, while acknowledging 12-hour shifts had a negative effect on fatigue, exhaustion, and their ability to achieve self-care (i.e. poor diet, no exercise).
Appropriate relaxation of non-pharmaceutical interventions minimizes the risk of a resurgence in SARS-CoV-2 infections in spite of the Delta variant
Authors: Koslow Wadim , Kühn Martin J. , Binder Sebastian , Klitz Margrit , Abele Daniel , Basermann Achim , Meyer-Hermann Michael
Published: July 2021

We analyze the relaxation of non-pharmaceutical interventions (NPIs) under an increasing number of vaccinations in Germany. For the spread of SARS-CoV-2 we employ a SIR-type model that accounts for age-dependence and includes realistic contact patterns between age groups. The implementation of NPIs occurs on changed contact patterns, improved isolation, or reduced infectiousness when, e.g., wearing masks. We account for spatial heterogeneity and commuting activities in between regions in Germany, and the testing of commuters is considered as a further NPI. We include the ongoing vaccination process and analyze the effect of the B.1.617.2 (Delta) variant, which is considered to be 40% − 60% more infectious then the currently dominant B.1.1.7 (Alpha) variant. We explore different opening scenarios under the ongoing vaccination process by assuming that local restrictions are either lifted in early July or August with or without continued wearing of masks and testing. Our results indicate that we can counteract the resurgence of SARS-CoV-2 despite the Delta variant with appropriate timing for the relaxation of NPIs. In all cases, however, school children are hit the hardest.

Author summary

One of the greatest challenges within the Covid-19 pandemic is to identify the timing and amount of non-pharmaceutical interventions (face masks, travel bans, school closures, etc). In the year 2021 more and more people are getting vaccinated. When can we finally lift all restrictions and stop wearing masks? In order to provide more insights to this question, we use a mathematical model which is capable of simulating the effects of non-pharmaceutical interventions in Germany while accounting for age-dependent factors as well as commuting activities between regions. We include the vaccination process and analyze the much more infectious Delta coronavirus variant. We simulate scenarios that consider the timing of the return to pre-pandemic contacts as well as when to suspend wearing masks and testing. Our results show that a later opening by 1 August in combination with masks and testing reduces the chance of a further infection wave considerably. From the retrospective view of the revision, we see that the rise in infections at the end of summer could have been well predicted by our scenarios that considered lifting of NPIs in July as it happened in many places. In all of our scenarios, the infection manifests in the younger age groups.
Using a population-based Kalman estimator to model the COVID-19 epidemic in France: estimating associations between disease transmission and non-pharmaceutical interventions
Authors: Collin Annabelle , Hejblum Boris P. , Vignals Carole , Lehot Laurent , Thiébaut Rodolphe , Moireau Philippe , Prague Mélanie
Published: July 2021

In response to the COVID-19 pandemic caused by SARS-CoV-2, governments have adopted a wide range of non-pharmaceutical interventions (NPI). These include stringent measures such as strict lockdowns, closing schools, bars and restaurants, curfews, and barrier gestures such as mask-wearing and social distancing. Deciphering the effectiveness of each NPI is critical to responding to future waves and outbreaks. To this end, we first develop a dynamic model of the French COVID-19 epidemics over a one-year period. We rely on a global extended Susceptible-Infectious-Recovered (SIR) mechanistic model of infection that includes a dynamic transmission rate over time. Multilevel data across French regions are integrated using random effects on the parameters of the mechanistic model, boosting statistical power by multiplying integrated observation series. We estimate the parameters using a new population-based statistical approach based on a Kalman filter, used for the first time in analysing real-world data. We then fit the estimated time-varying transmission rate using a regression model that depends on the NPIs while accounting for vaccination coverage, the occurrence of variants of concern (VoC), and seasonal weather conditions. We show that all NPIs considered have an independent significant association with transmission rates. In addition, we show a strong association between weather conditions that reduces transmission in summer, and we also estimate increased transmissibility of VoC.
Exploring the relationship between schizophrenia and cardiovascular disease: A genetic correlation and multivariable Mendelian randomization study
Authors: Veeneman Rada R , Vermeulen Jentien M , Abdellaoui Abdel , Sanderson Eleanor , Wootton Robyn E , Tadros Rafik , Bezzina Connie R , Denys Damiaan , Munafò Marcus R , Verweij Karin JH , Treur Jorien L
Published: July 2021

Importance

Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to fully unravel the nature of this relationship.

Objective

Investigate genetic correlations and potential bi-directional effects between liability to schizophrenia and CVD.

Design, setting, and participants

We obtained summary-data of genome-wide-association studies of schizophrenia (N=130,644), heart failure (N=977,323), coronary artery disease (N=332,477), systolic and diastolic blood pressure (N=757,601), heart rate variability (N=46,952), QT interval (N=103,331), early repolarization and dilated cardiomyopathy ECG patterns (N=63,700). We computed genetic correlations with linkage disequilibrium score regression and conducted bi-directional Mendelian randomization (MR). With multivariable MR, we investigated whether associations were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. To ensure robustness, we applied a range of sensitivity methods.

Main outcomes and measures

Schizophrenia, heart failure, coronary artery disease, systolic blood pressure, diastolic blood pressure, heart rate variability, QT interval, early repolarization, dilated cardiomyopathy.

Results

Genetic correlations between liability to schizophrenia and CVD were close to zero (−0.02 to 0.04). With MR, we found robust evidence that liability to schizophrenia increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization risk, largely mediated by BMI and lipid levels. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting previous studies. In the other direction, there was weak evidence that higher systolic, but not diastolic, blood pressure increases schizophrenia risk.

Conclusions and relevance

Our findings indicate that liability to schizophrenia increases the risk of heart failure, and that this is not mediated by key health behaviours. This is consistent with the notion that schizophrenia is characterised by a systemic dysregulation of the body (including inflammation and oxidative stress) with detrimental effects on the heart. To decrease cardiovascular mortality among schizophrenia patients, priority should lie with optimal treatment and interventions in early stages of psychoses. We also identified early repolarization, currently understudied, as a potential CVD marker among patients with schizophrenia.
Time-to-event assessment for the discovery of the proper prognostic value of clinical biomarkers optimized for COVID-19
Authors: Ferreira José Raniery , Ribeiro Victor Henrique Alves , Cossetin Marcelo , Figueredo Marcus Vinícius Mazega , Cardoso Carolina Queiroz , Almeida Bernardo Montesanti
Published: July 2021

In the early days of the pandemic, clinical biomarkers for COVID -19 have been investigated to predict patient mortality. A decision tree has been proposed previously comprising three variables, i.e., lactic dehydrogenase (LDH), high-sensitivity C-reactive protein (CRP), and lymphocyte percentage, with more than 90% accuracy in a public cohort. In this work, we highlighted the importance of the cohort made publicly available and complemented the findings by incorporating further evaluation. Results confirmed poor short-term prognosis to abnormal levels of some laboratorial indicators, such as LDH, CRP, lymphocytes, interleukin-6, and procalcitonin. In addition, our findings provide insights into COVID-19 research, such as key levels of fibrin degradation products, which are directly associated with the Dimerized plasmin fragment D and could indicate active coagulation and thrombosis. Still, we highlight here the prognostic value of interleukin-6, a cytokine that induces inflammatory response and may serve as a predictive biomarker.
Awareness, treatment, and control of diabetes in Bangladesh: evidence from the Bangladesh Demographic and Health Survey 2017/18
Authors: Khan Md. Nuruzzaman , Oldroyd John C. , Hossain Mohammad Bellal , Islam Rakibul M.
Published: July 2021

Background

The prevalence of diabetes is increasing in Bangladesh; however, the management of diabetes assessed by diabetes awareness, treatment, and control, remains poor. We aimed to estimate the age-standardised prevalence of awareness, treatment, and control of diabetes and its associated factors.

Methods

In this cross-sectional study, data from 1,174 Bangladeshi adults aged 18 years and older available from the most recent nationally representative Bangladesh Demographic and Health Survey (BDHS) 2017-18 were analysed. Awareness, treatment, and control of diabetes were our outcomes of interest. Age-stadarised prevalence of awareness, treatment, and control were estimated using the direct standardisation. Multilevel mixed-effects Poisson regression models were used to identify factors associated with awareness, treatment, and control of diabetes.

Results

Among those with diabetes (n=1,174), only 30.9% (95% CI, 28.2-33.6) were aware that they had the condition, and 28.2% (95% CI, 25.6-30.7) were on treatment. Among those treated for diabetes, only 26.5% (95% CI, 19.5-33.5) had controlled diabetes. Prevalences for awareness, treatment and control were even lower in men than women. Factors positively associated with awareness and treatment were increasing age and hypertension while factors negatively associated with awareness and treatment were being men and having lower education. Factors associated with poor control were secondary education and residing in Rajshahi and Rangpur divisions.

Conclusion

This study provides evidence of poor management of diabetes in Bangladesh, especially in men. Less than one-third of the people with diabetes were aware of their condition. Just over one-fourth of the people with diabetes were on treatment, and those were treated one-fourth had controlled diabetes. Interventions targeting younger people, in particular men and those with lower education, are urgently needed. The government needs to strengthen diabetes management programs within primary health care and address structural factors including the costs of diabetes care to improve awareness, treatment, and control of diabetes in Bangladesh.
SARS-CoV-2 variants of concern exhibit reduced sensitivity to live-virus neutralization in sera from CoronaVac vaccinees and naturally infected COVID-19 patients
Authors: Vacharathit Vimvara , Aiewsakun Pakorn , Manopwisedjaroen Suwimon , Srisaowakarn Chanya , Laopanupong Thanida , Ludowyke Natali , Phuphuakrat Angsana , Setthaudom Chavachol , Ekronarongchai Supanuch , Srichatrapimuk Sirawat , Wongsirisin Pattama , Sangrajrang Suleeporn , Imsuwansri Thanarath , Kirdlarp Suppachok , Nualkaew Sureeporn , Sensorn Insee , Sawaengdee Waritta , Wichukchinda Nuanjun , Sungkanuparph Somnuek , Chantratita Wasun , Kunakorn Mongkol , Rojanamatin Jinda , Hongeng Suradej , Thitithanyanont Arunee
Published: July 2021

Recent surges in SARS-CoV-2 variants of concern (VOCs) call for the need to evaluate levels of vaccine-and infection-induced SARS-CoV-2 neutralizing antibodies (NAbs). CoronaVac (Sinovac Biotech, Beijing, China) is currently being used for mass vaccination in Thailand as well as other low-income countries. Three VOCs currently circulating within Thailand include the B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) strains. We assessed NAb potency against the prototypic strain containing the original spike sequence (WT) compared to that against the 3 VOCs using sera derived from a cohort of healthcare workers who received a full 2-dose regimen of CoronaVac. Sera from two other cohorts consisting of COVID-19 patients who had been hospitalized in 2020 and 2021 were evaluated for comparison. We found that, despite equally robust production of S1-RBD-binding IgG and 100% seropositivity, sera from both CoronaVac vaccinees and naturally infected individuals had significantly reduced neutralizing capacity against all 3 VOCs compared to WT. Strikingly, NAb titers against Alpha and Beta were comparable, but Delta appears to be significantly more refractory to NAbs in all groups. Our results may help inform on CoronaVac NAb-inducing capacity, which is a proxy for vaccine efficacy, in the context of the WT strain and 3 VOCs. Our results also have critical implications for public health decision-makers who may need to maintain efficient mitigation strategies amid a potentially high risk for infection with VOCs even in those who have been previously infected.
Mapping First to Second wave transition of covid19 Indian data via Sigmoid function and prediction of Third wave
Authors: Mondal Supriya , Ghosh Sabyasachi
Published: July 2021

Understanding first and second wave of covid19 Indian data along with its few selective states, we have realized a transition between two Sigmoid pattern with twice larger growth parameter and maximum values of cumulative data. As a result of those transition, time duration of second wave shrink to half of that first wave with four times larger peak values. It is really interesting that the facts can be easily understood by simple algebraic expressions of Sigmoid function. After understanding the crossing zone between first and second wave curves, a third wave Sigmoid pattern is guessed.
STUDY OF BLOOD GROUP ANALYSIS AND ITS CORRELATION WITH LYMPHOPENIA IN COVID-19 INFECTED CASES – OUR EXPERIENCE IN TERITARY CARE HOSPITAL
Authors: Ravuri Swarupa , Cigiri Saritha , Kalangi Harika , Jeshtadi Anunayi , Kumar K.Nithesh , Krishna Nampally Vamshi , Bacchu Srilatha , Sudhakar K.
Published: July 2021

AIMS AND OBJECTIVES

To study the distribution and frequencies of ABO and Rhesus (Rh) blood groups among confirmed cases of Covid-19 infection. We also studied the relation between ABO blood group system and lymphopenia and studied the gender association in COVID-19 patients.

METHODES

A hospital based retrospective study was conducted at Government Medical College Suryapet from 01 Aug 2020 to 30 Sep 2020. A total of 200 Covid cases were included in the study who came to the hospital with the complaints of Fever, Sore throat, Body Pains, Cough, Breathlessness, Diarrhoea etc. Patients confirmed Covid infection was tested for blood grouping and RH typing by using forward blood grouping with the help of commercially available standard monoclonal antisera. CBP was processed in sysmax 5 part Haematology analyser. Blood group frequency was tested also assed the gender association, Covid patients presents with lymphopenia the relation between the ABO blood group and lymphocyte count was determined.

RESULTS

Males were more compared to the females .Middle aged group male patients were more commonly involved. Most predominant blood group was group B 79(39.5%), group O 78(39%),group A 37(18.5%), group AB 6(3%),most of them were 190 (95%)Rh positive, only 10 Rh negative (5%).To assess the Lymphopenia in our study we divided the absolute lymphocyte count into 5 groups. Group 1 cases are more 58 (29%), Group 2 91(45.5%), Group 3 30 (15%), Group 4 16(8%), Group 5 5(2.5%).

CONCLUSION

Male patients with blood group B were more compared to other blood groups however more number of studies are necessary to confirm these findings in a larger sample and among individuals of different ethnicities.
Evidence of SARS-Cov-2-specific memory B cells six months after vaccination with BNT162b2 mRNA vaccine
Authors: Ciabattini Annalisa , Pastore Gabiria , Fiorino Fabio , Polvere Jacopo , Lucchesi Simone , Pettini Elena , Auddino Stefano , Rancan Ilaria , Durante Miriam , Miscia Michele , Rossetti Barbara , Fabbiani Massimiliano , Montagnani Francesca , Medaglini Donata
Published: July 2021

SARS-CoV-2 mRNA vaccines have demonstrated high efficacy and immunogenicity, but limited information is currently available on memory B cells generation and long-term persistence. Here, we investigated Spike-specific memory B cells and humoral responses in 145 subjects, up to six months after the BNT162b2 vaccine (Comirnaty) administration. Spike-specific antibody titers peaked 7 days after the second dose and significant titers and neutralizing activity were still observed after six months, despite a progressive decline over time. Concomitant to antibody reduction, Spike-specific memory B cells, mostly IgG class-switched, increased in blood of vaccinees and persisted six months after vaccination. Following in vitro restimulation, circulating memory B cells reactivated and produced Spike-specific antibodies. A high frequency of Spike-specific IgG+ plasmablasts, identified by computational analysis 7 days after boost, positively correlated with the generation of IgG+ memory B cells at six months.

These data demonstrate that mRNA BNT162b2 vaccine elicits strong B cell immunity with Spike-specific memory B cells that still persist six months after vaccination, playing a crucial role for rapid response to SARS-CoV-2 virus encounter.

One Sentence Summary

mRNA BNT162b2 vaccine elicits persistent spike-specific memory B cells crucial for rapid response to SARS-CoV-2 virus encounter
Comparing organ donation decisions for next-of-kin versus the self: Results of a national survey
Authors: Liu Christopher W. , Chen Lynn N. , Anwar Amalina , Zhao Boyu Lu , Lai Clin K. Y. , Ng Wei Heng , Suhitharan Thangavelautham , Ho Vui Kian , Liu Jean C. J.
Published: July 2021

Objectives

Intensive care audits point to family refusal as a major barrier to organ donation. In this study, we sought to understand refusal by accounting for the decision-maker’s mindset. This focused on: (1) how decisions compare when made on behalf of a relative (versus the self); and (2) confidence in decisions made for family members.

Design

Cross-sectional survey in Singapore.

Setting

Participants were recruited from community settings via door-to-door sampling and community eateries.

Participants

973 adults who qualified as organ donors in Singapore.

Results

Although 68.1% of participants were willing to donate their own organs, only 51.8% were willing to donate a relative’s. Using machine learning, we found that consistency was predicted by: (i) religion, and (ii) fears about organ donation. Conversely, participants who were willing to donate their own organs but not their relative’s were less driven by these factors, and may instead have resorted to heuristics in decision-making. Finally, we observed how individuals were overconfident in their decision-making abilities: although 78% had never discussed organ donation with their relatives, the large majority expressed high confidence that they would respect their relatives’ wishes upon death.

Conclusions

These findings underscore the distinct psychological processes involved when donation decisions are made for family members. Amidst a global shortage of organ donors, addressing the decision-maker’s mindset (e.g., overconfidence, the use of heuristics) may be key to actualizing potential donors identified in intensive care units.

Strengths and Limitations of this Study

We used a multi-disciplinary approach combining psychology theory and machine learning analyses to understand family refusal in a novel manner.

We directly compared organ donation decisions made from the self versus for next-of-kin, and also documented overconfidence in the decision-making process.

The study was conducted in an urban setting and may not apply to rural contexts.
Set-based rare variant association tests for biobank scale sequencing data sets
Authors: Zhou Wei , Bi Wenjian , Zhao Zhangchen , Dey Kushal K. , Jagadeesh Karthik A. , Karczewski Konrad J. , Daly Mark J. , Neale Benjamin M. , Lee Seunggeun
Published: July 2021

UK Biobank has released the large-scale whole-exome sequencing (WES) data, but the best practices remain unclear for rare variant tests, and an existing approach, SAIGE-GENE, can have inflated type I error rates with high computation costs. Here, we propose SAIGE-GENE+ with greatly improved type I error control and computational efficiency compared to SAIGE-GENE. In the analysis of UKBB WES data of 30 quantitative and 141 binary traits, SAIGE-GENE+ identified 551 gene-phenotype associations. In addition, we showed that incorporating multiple MAF cutoffs and functional annotations can help identify novel gene-phenotype associations.
Predictions of biodiversity are improved by integrating trait-based competition with abiotic filtering
Authors: Chalmandrier Loïc , Stouffer Daniel B. , Purcell Adam S. T. , Lee William G. , Tanentzap Andrew J. , Laughlin Daniel C.
Published: July 2021

All organisms must simultaneously tolerate the environment and access limiting resources if they are to persist. Otherwise they go extinct. Approaches to understanding environmental tolerance and resource competition have generally been developed independently. Consequently, integrating the factors that determine abiotic tolerance with those that affect competitive interactions to model species abundances and community structure remains an unresolved challenge. This is likely the reason why current models of community assembly do not accurately predict species abundances and dynamics. Here, we introduce a new synthetic framework that models both abiotic tolerance and biotic competition by using functional traits, which are phenotypic attributes that influence organism fitness. First, our framework estimates species carrying capacities that vary along abiotic gradients based on whether the phenotype tolerates the local environment. Second, it estimates pairwise competitive interactions as a function of multidimensional trait differences between species and determines which trait combinations produce the most competitive phenotypes. We demonstrate that our combined approach more than doubles the explained variance of species covers in a wetland community compared to the model of abiotic tolerances alone. Trait-based integration of competitive interactions and abiotic filtering improves our ability to predict species abundances across space, bringing us closer to more accurate predictions of biodiversity structure in a changing world.
Electrophysiological correlates of proactive and reactive inhibition in a modified visual Go/NoGo task
Authors: Kutý Jiří , Damborská Alena , Linhartová Pavla , Lamoš Martin , Jeřábková Barbora , Rudišinová Daniela , Bareš Martin , Kašpárek Tomáš
Published: July 2021

Impulse control is crucial for everyday functioning in modern society. People with borderline personality disorder (BPD) suffer from impulse control impairment. According to the theory of dual mechanisms of control, motor impulse control can be divided into proactive and reactive modes. Proactive inhibition is involved before an event that might require inhibitory control. Reactive inhibition is initiated after the occurrence of an event that requires inhibitory control. Few studies have focused on proactive inhibition in relation to impaired impulse control, moreover electrophysiological evidence is scarce. Therefore, in the search for electrophysiological correlates of proactive and reactive inhibitions, we assessed event-related potentials elicited during a modified emotionally neutral visual Go/NoGo task in 28 clinically impulsive BPD patients and 35 healthy control (HC) subjects. In both groups, proactive inhibition was associated with enhanced late prestimulus activity and a suppressed poststimulus N2 component. In both groups, reactive inhibition was associated with enhanced poststimulus N2 and P3 components. We found no electrophysiological differences between HC subjects and BPD patients and both groups performed similarly in the task. Hence, the clinically observed impulse control impairment in BPD might act through different mechanisms other than altered inhibitory control in an emotionally neutral task.
Plexin-A2 Promotes The Proliferation And The Development Of Tumors From Glioblastoma Derived Cells
Authors: Toledano Shira , Sabag Adi D. , liburkin-Dan Tanya , Kessler Ofra , Neufeld Gera
Published: July 2021

The semaphorin guidance factors receptor Plexin-A2 transduces sema6A and sema6B signals and when associated with neuropilins can also transduce sema3C signals. Inhibition of plexin-A2 expression in U87MG glioblastoma cells resulted in strong inhibition of cell proliferation and tumor forming ability. Knock-out of the plexin-A2 gene using CRISPR/Cas9 also inhibited cell proliferation which was rescued following re-expression of the plexin-A2 cDNA or expression of a truncated plexin-A2 lacking the extracellular domain. Inhibition of plexin-A2 expression resulted in cell cycle arrest at the G2/M stage, and was accompanied by changes in cytoskeletal organization, cell flattening, and by the expression of senescence associated β-galactosidase. It was also associated with reduced AKT phosphorylation and enhanced phosphorylation of p38MAPK. We find that the pro-proliferative effects of plexin-A2 are mediated by FARP2 and FYN since mutations in the FARP2 binding domain of plexin-A2 or in the FYN phosphorylation sites of plexin-A2 compromised the rescue of the proliferative activity by the plexin-A2 intracellular domain. Our results suggest that plexin-A2 may represent a novel target for the development of anti-tumorigenic therapeutics.
Water-soluble tocopherol derivatives inhibit SARS-CoV-2 RNA-dependent RNA polymerase
Authors: Pacl Hayden T. , Tipper Jennifer L. , Sevalkar Ritesh R. , Crouse Andrew , Crowder Camerron ,   UAB Precision Medicine Institute, Ahmad Shama , Ahmad Aftab , Holder Gillian D. , Kuhlman Charles J. , Chinta Krishna C. , Nadeem Sajid , Green Todd J. , Petit Chad M. , Steyn Adrie J.C. , Might Matthew , Harrod Kevin S.
Published: July 2021

The recent emergence of a novel coronavirus, SARS-CoV-2, has led to the global pandemic of the severe disease COVID-19 in humans. While efforts to quickly identify effective antiviral therapies have focused largely on repurposing existing drugs1–4, the current standard of care, remdesivir, remains the only authorized antiviral intervention of COVID-19 and provides only modest clinical benefits5. Here we show that water-soluble derivatives of α-tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Through an artificial-intelligence-driven in silico screen and in vitro viral inhibition assay, we identified D-α-tocopherol polyethylene glycol succinate (TPGS) as an effective antiviral against SARS-CoV-2 and β-coronaviruses more broadly that also displays strong synergy with remdesivir. We subsequently determined that TPGS and other water-soluble derivatives of α-tocopherol inhibit the transcriptional activity of purified SARS-CoV-2 RdRp and identified affinity binding sites for these compounds within a conserved, hydrophobic interface between SARS-CoV-2 nonstructural protein 7 and nonstructural protein 8 that is functionally implicated in the assembly of the SARS-CoV-2 RdRp6. In summary, we conclude that solubilizing modifications to α-tocopherol allow it to interact with the SARS-CoV-2 RdRp, making it an effective antiviral molecule alone and even more so in combination with remdesivir. These findings are significant given that many tocopherol derivatives, including TPGS, are considered safe for humans, orally bioavailable, and dramatically enhance the activity of the only approved antiviral for SARS-CoV-2 infection7–9.
Perturb-map enables CRISPR genomics with spatial resolution and identifies regulators of tumor immune composition
Authors: Dhainaut Maxime , Rose Samuel A , Akturk Guray , Wroblewska Aleksandra , Park Eun Sook , Nielsen Sebastian R , Buckup Mark , Roudko Vladimir , Pia Luisanna , Le Berichel Jessica , Bektesevic Anela , Lee Brian H , Baccarini Alessia , Bhardwaj Nina , Rahman Adeeb H , Gnjatic Sacha , Pe’er Dana , Merad Miriam , Brown Brian D
Published: July 2021

The cellular architecture of a tumor, particularly immune composition, has a major impact on cancer outcome, and thus there is an interest in identifying genes that control the tumor microenvironment (TME). While CRISPR screens are helping uncover genes regulating many cell-intrinsic processes, existing approaches are suboptimal for identifying gene functions operating extracellularly or within a tissue context. To address this, we developed an approach for spatial functional genomics called Perturb-map, which utilizes protein barcodes (Pro-Code) to enable spatial detection of barcoded cells within tissue. We show >120 Pro-Codes can be imaged within a tumor, facilitating spatial mapping of 100s of cancer clones. We applied Perturb-map to knockout dozens of genes in parallel in a mouse model of lung cancer and simultaneously assessed how each knockout influenced tumor growth, histopathology, and immune composition. Additionally, we paired Perturb-map and spatial transcriptomics for unbiased molecular analysis of Pro-Code/CRISPR lesions. Our studies found in Tgfbr2 knockout lesions, the TME was converted to a mucinous state and T-cells excluded, which was concomitant with increased TGFβ expression and pathway activation, suggesting Tgfbr2 loss on lung cancer cells enhanced suppressive effects of TGFβ on the TME. These studies establish Perturb-map for functional genomics within a tissue at single cell-resolution with spatial architecture preserved.