bluuebunny/crossref_metadata_2025 huggingface dataset:
Interventions to control nosocomial transmission of SARS-CoV-2: a modelling study
Authors: Pham Thi Mui , Tahir Hannan , van de Wijgert Janneke H.H.M. , Van der Roest Bastiaan , Ellerbroek Pauline , Bonten Marc J.M. , Bootsma Martin C.J. , Kretzschmar Mirjam E.
Published: March 2021

Background

Emergence of more transmissible SARS-CoV-2 variants requires more efficient control measures to limit nosocomial transmission and maintain healthcare capacities during pandemic waves. Yet, the relative importance of different strategies is unknown.

Methods

We developed an agent-based model and compared the impact of personal protective equipment (PPE), screening of healthcare workers (HCWs), contact tracing of symptomatic HCWs, and restricting HCWs from working in multiple units (HCW cohorting) on nosocomial SARS-CoV-2 transmission. The model was fit on hospital data from the first wave in the Netherlands (February until August 2020) and assumed that HCWs used 90% effective PPE in COVID-19 wards and self-isolated at home for seven days immediately upon symptom onset. Intervention effects on the effective reproduction number (RE), HCW absenteeism and the proportion of infected individuals among tested individuals (positivity rate) were estimated for a more transmissible variant.

Results

Introduction of a variant with 56% higher transmissibility increased – all other variables kept constant –REfrom 0.4 to 0.65 (+63%) and nosocomial transmissions by 303%, mainly because of more transmissions caused by pre-symptomatic patients and HCWs. Compared to baseline, PPE use in all hospital wards (assuming 90% effectiveness) reducedREby 85% and absenteeism by 57%. Screening HCWs every three days with perfect test sensitivity reducedREby 67%, yielding a maximum test positivity rate of 5%. Screening HCWs every three or seven days assuming time-varying test sensitivities reducedREby 9% and 3%, respectively. Contact tracing reducedREby at least 32% and achieved higher test positivity rates than screening interventions. HCW cohorting reducedREby 5%. Sensitivity analyses for 50% and 70% effectiveness of PPE use did not change interpretation.

Conclusions

In response to the emergence of more transmissible SARS-CoV-2 variants, PPE use in all hospital wards might still be most effective in preventing nosocomial transmission. Regular screening and contact tracing of HCWs are also effective interventions, but critically depend on the sensitivity of the diagnostic test used.
Changes in eating habits and lifestyles in Peruvian population during social isolation by the COVID-19 pandemic
Authors: Huancahuire-Vega Salomón , Newball-Noriega Edda E. , Rojas-Humpire Ricardo , Saintila Jacksaint , Vásquez Mery Rodriguez , Ruiz-Mamani Percy. G. , Morales-García Wilter C. , White Michael
Published: March 2021

Background

The COVID-19 pandemic caused that some governments have implemented house confinement measures with probable consequences on lifestyle, particularly affecting eating habits, physical activity, sleep quality, and mental health.

Objectives

The aim of this study was to assess the frequency of lifestyles, physical activity and sleep characteristics, as well as changes in eating habits in the Peruvian population during COVID-19 pandemic.

Methods

A Cross-sectional descriptive study was performed. We analyzed adults from Peru between July to August 2020 based on an online self-administered questionnaire divided into sociodemographic, anthropometrics and COVID-19 diagnostic reported, lifestyle habits and frequency of consumption of foods.

Findings

During confinement by COVID-19, 1176 participants were studied, 39% were student, 37.5% were workers and 46% were assert not to work. The population asserted gain weight (1 to 3 Kg) and 35.7% were overweight. The lifestyles habits showed that 54.8% affirmed to doing physical activity and a large proportion (37.2%) asserted sleep less. The Peruvian population presented a main feeding patter of breakfast (95.7%), lunch (97.5%), dinner (89.1%) and brunch (44.9%). Likewise, feeding habits before and during COVID-19 pandemic showed that vegetables (OR:1.56, CI95% 1.21 - 200), fruit (OR: 1.42, CI95% 1.10 – 1.81), legumes (OR:1.67, CI95% 1.23 – 2.28) and eggs (OR: 2.00, CI95% 1.52 – 2.65) presented significantly consumption increase during social isolation, while bakery products (OR: 0.74, CI95% 0.56 – 0.97), meat, snack, refreshment and fast-food decrease consumption. Other food no significant differences were presented.

Conclusion

This study in a Peruvian population showed an important frequency of overweight and sleep disorders. There was a slight increase in physical activity despite the social isolation measures and an increase in health eating habits, nevertheless a majority reported gaining weight.
HEARING MORE TO HEAR LESS: A SCOPING REVIEW OF HEARING AIDS FOR TINNITUS RELIEF
Authors: Jacquemin Laure , Gilles Annick , Shekhawat Giriraj Singh
Published: March 2021

Background

Tinnitus, the perception of a sound in absence of an external auditory source, can significantly impact ones’ quality of life. As tinnitus is often associated with hearing loss, hearing aids have been proposed for tinnitus relief in literature for more than 70 years. While there is a long history of clinical work and research on this topic, there is a need for recent literature to be reviewed and guide decision making in tinnitus management.

Objective

The aim of this scoping review is to provide an update of the available evidence on hearing aids for tinnitus, focusing on the effect of sound amplification, to draw conclusions for clinical practice and identify gaps in the field. A consultation exercise was included to discuss current issues that practitioners and carers themselves face but remain under-researched.

Design

This scoping review was conducted based on the six-stage framework of Arksey et al. (2005). Studies were included if they investigated hearing aids for tinnitus and were published after 2011. Databases of PubMed and Scopus were explored on the 16th of November 2020. The search was limited to English manuscripts. A total of 28 primary research studies were selected.

Results

Positive results of hearing aids for tinnitus relief were shown by 68 % of the studies, whereas 14 % demonstrated no change in tinnitus perception. As the quality of the evidence across studies was variable, no consensus can be reached regarding the use of hearing aids as a treatment for tinnitus. Nevertheless, recent studies were more likely to focus on optimizing the effect of hearing aids and better predicting which tinnitus patients benefit from hearing aids. The experts stated that the findings were in agreement with their view on the scientific evidence and they emphasized the importance of reaching consensus.

Conclusions

The majority of the studies supported the use of hearing aids for tinnitus relief. Hence, there was some scientific support for it, but the quality of evidence was questioned. Stronger methodology in future studies is needed to reach consensus and support clinical guidelines development.
COVID-19 lockdowns may reduce resistance genes diversity in the human microbiome and the need for antibiotics
Authors: Rebelo João S. , Domingues Célia P. F. , Dionisio Francisco , Gomes Manuel C. , Botelho Ana , Nogueira Teresa
Published: March 2021

2.

Recently, much attention has been paid to the COVID-19 pandemic, yet bacterial resistance to antibiotics remains a serious and unsolved public health problem, which kills thousands of people annually, being an insidious and silent pandemic. In this study, we explored the idea of confinement and the tightening of the hygiene measures to contain the spreading of coronavirus, to simulate the effect that it has on lowering the spreading of pathogenic bacteria in a human network, and on the need to use antibiotics. For that, we used computational biology to generate simulations.
Genomic epidemiology of SARS-CoV-2 in the United Arab Emirates reveals novel virus mutation, patterns of co-infection and tissue specific host innate immune response
Authors: Liu Rong , Wu Pei , Ogrodzki Pauline , Mahmoud Sally , Liang Ke , Liu Pengjuan , Francis Stephen S. , Khalak Hanif , Liu Denghui , Li Junhua , Ma Tao , Chen Fang , Liu Weibin , Huang Xinyu , He Wenjun , Yuan Zhaorong , Qiao Nan , Meng Xin , Alqarni Budoor , Quilez Javier , Kusuma Vinay , Lin Long , Jin Xin , Yang Chongguang , Anton Xavier , Koshy Ashish , Yang Huanming , Xu Xun , Wang Jian , Xiao Peng , Al Kaabi Nawal Ahmed Mohamed , Fasihuddin Mohammed Saifuddin , Selvaraj Francis Amirtharaj , Weber Stefan , Al Hosani Farida Ismail , Liu Siyang , Zaher Walid Abbas
Published: March 2021

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1,067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation.
Higher viral load drives infrequent SARS-CoV-2 transmission between asymptomatic residence hall roommates
Authors: Bjorkman Kristen K. , Saldi Tassa K. , Lasda Erika , Bauer Leisha Conners , Kovarik Jennifer , Gonzales Patrick K. , Fink Morgan R. , Tat Kimngan L. , Hager Cole R. , Davis Jack C. , Ozeroff Christopher D. , Brisson Gloria R. , Larremore Daniel B. , Leinwand Leslie A. , McQueen Matthew B. , Parker Roy
Published: March 2021

In 2019-2020, the COVID-19 pandemic spread to over 200 countries in less than six months. To understand the basis of this aggressive spread, it is essential to determine the transmission rate and define the factors that increase the risk of transmission. One complication is the large fraction of asymptomatic cases, particularly in young populations: these individuals have viral loads indistinguishable from symptomatic people and do transmit the SARS-CoV-2 virus, but they often go undetected. As university students living in residence halls commonly share a small living space with roommates, some schools established regular, high density testing programs to mitigate on-campus spread. In this study, we analyzed longitudinal testing data of residence hall students at the University of Colorado Boulder. We observed that students in single rooms were infected at a lower rate than students in multiple occupancy rooms. However, this was not due to high rates of transmission between roommates, which only occurred approximately 20% of the time. Since these cases were usually asymptomatic at the time of diagnosis, this provides further evidence for asymptomatic transmission. Notably, individuals who likely transmitted to their roommates had an average viral load ∼6.5 times higher than individuals who did not. Although students were moved to separate isolation rooms after diagnosis, there was no difference in time to isolation between these cases with or without transmission. This analysis argues that inter-roommate transmission occurs in a minority of cases in university residence halls and provides strong correlative evidence that viral load can be proportional to the probability of transmission.
Performance of popular pulse oximeters compared with simultaneous arterial oxygen saturation or clinical-grade pulse oximetry: a cross-sectional validation study in intensive care patients
Authors: Harskamp Ralf E. , Bekker Luuk , Himmelreich Jelle C.L. , De Clercq Lukas , Karregat Evert P.M. , Sleeswijk Mengalvio E. , Lucassen Wim A.M.
Published: March 2021

Background

The demand for pulse oximeters is high in the current COVID-19 pandemic. Despite their popularity, clinical studies to evaluate the reliability in obtaining information on a patient’s oxygenation status, are lacking.

Aim

To evaluate the performance of pulse oximeters under clinical conditions, with arterial blood gas measurement (SaO2) as reference standard.

Methods

We studied the accuracy of ten top-selling pulse oximeters in Europe and the USA in an intensive care population at the Flevoziekenhuis in Almere, the Netherlands. The studied pulse oximeters were: AFAC FS10D, AGPTEK FS10C, ANAPULSE ANP 100, Cocobear, Contec CMS50D1, HYLOGY MD-H37, Mommed YM101, PRCMISEMED F4PRO, PULOX PO-200, and Zacurate Pro Series 500DL. Adult patients in whom an SaO2 measurement was obtained as part of routine care were asked for inclusion. Directly after obtaining the SaO2 blood sample we obtained the pulse oximeter readings (SpO2) of the investigational devices, in random order. Outcomes were bias (SpO2 – SaO2) mean, root mean square difference (ARMS), mean absolute error (MAE), and accuracy in identifying hypoxemia (SaO2≤90%). As a clinical index test, we included a hospital-grade SpO2-monitor.

Results

In 35 consecutive patients we obtained 2,258 SpO2-readings and 234 SaO2-samples. Mean bias ranged from −0.6 to −4.8. None of the pulse oximeters had an ARMS≤3%, the requirement set by ISO-standards and required for FDA 501(k) clearance. The MAE ranged from 2.3 to 5.1, and 5 out of 10 pulse oximeters met the requirements of ≤3%. For hypoxemia, negative predictive values were 98-99%. Positive predictive values ranged from 11-30%. Highest accuracy (95%CI) were found for Contec CMS50D1; 91% (86-94) and Zacurate Pro Series 500DL; 90% (85-94). The hospital-grade SpO2-monitor had an ARMS of 3.0 and MAE of 1.9, and an accuracy of 95% (91-97%).

Conclusion

Direct-to-consumer pulse oximeters do not meet ISO-standards required for FDA-clearance, but can accurately rule out hypoxemia.
Feasibility of Social Media Recruitment for Orofacial Cleft Genetic Research
Authors: Carlock Grace , Manning Kelly , Leslie Elizabeth J.
Published: March 2021

Objective

This study assessed the feasibility of unpaid social media (SM) advertising to recruit participants affected with an orofacial cleft (OFC) for a genetic study.

Design

This paper is a retrospective analysis of study recruitment based on enrollment and participation in a genetic study. Participants completed a series of enrollment surveys, provided saliva samples for genetic analysis, and completed post-participation feedback surveys.

Participants

Participants signed up for the study following SM advertisement. Participants were eligible if: they or a minor in their care were affected by an OFC, the affected participant was not adopted, and the mother of the affected individual had not taken anti-seizure medication during pregnancy. 313 individuals completed initial screening surveys; 306 participants were eligible. 263 individuals completed all online surveys and were sent DNA sample kits. 162 subject DNA samples were returned.

Main Outcome Measures

Success of recruitment was evaluated as number of enrolled participants and return rate for DNA samples.

Results

263 OFC-affected individuals completed the screening process in the first 12 months of recruitment. 162 of 263 affected subject DNA samples were returned within 12 months of sending, for a return rate of 62%. Approximately two-thirds (66.3%) of all returned samples were sent back within the first 6 weeks after receiving DNA kits.

Conclusions

Unpaid SM advertising enabled the recruitment of a large cohort of participants in a short time (12 months). SM recruitment was inexpensive and effective for recruiting participants for a genetic study.
Interferons Reshape the 3D Conformation and Accessibility of Macrophage Chromatin
Authors: Platanitis Ekaterini , Grüner Stephan , Geetha Aarathy Ravi Sundar Jose , Boccuni Laura , Vogt Alexander , Novachkova Maria , Sommer Andreas , Müller Mathias , Decker Thomas
Published: March 2021

Engagement of macrophages in innate immune responses is directed and enhanced by type I and type II interferons. An essential component of IFN activity is the use of JAK-STAT signal transduction for the transcriptional control of interferon-stimulated genes (ISG). Here, we study the immediate early nuclear response to type I IFN and IFN-γ in murine macrophages. Despite their distinct immunological activities, both IFN types triggered highly overlapping epigenomic and transcriptional changes. These changes included a rapid rearrangement of the 3D chromatin organization and an increase of DNA accessibility at ISG loci. ISGF3, the major transcriptional regulator of ISG, controlled homeostatic as well as induced-state DNA accessibility at a subset of ISG. Increases in DNA accessibility correlated with the appearance of activating histone marks at surrounding nucleosomes. Collectively our data emphasize changes in the three-dimensional nuclear space and epigenome as an important facet of transcriptional control by the IFN-induced JAK-STAT pathway.
PathogenicMAST3variants in the STK domain are associated with epilepsy
Authors: Spinelli Egidio , Christensen Kyle R , Bryant Emily , Schneider Amy , Rakotomamonjy Jennifer , Muir Alison M , Giannelli Jessica , Littlejohn Rebecca O , Roeder Elizabeth R , Schmidt Berkley , Wilson William G , Marco Elysa J , Iwama Kazuhiro , Kumada Satoko , Pisano Tiziano , Barba Carmen , Brilstra Eva H , van Jaarsveld Richard H , Matsumoto Naomichi , Rodan Lance H , McWalter Kirsty , Guerrini Renzo , Scheffer Ingrid E , Mefford Heather C , Mandelstam Simone , Laux Linda , Millichap John J , Guemez-Gamboa Alicia , Nairn Angus C , Carvill Gemma L
Published: March 2021

Objective

The MAST family of microtubule-associated serine-threonine kinases (STK) have distinct expression patterns in the developing and mature human and mouse brain. To date, onlyMAST1has been associated with neurological disease, withde novovariants in individuals with a neurodevelopmental disorder, including a mega corpus callosum.

Methods

Using exome sequencing we identifyMAST3missense variants in individuals with epilepsy. We also assess the effect of these variants on the ability of MAST3 to phosphorylate the target gene product ARPP-16 in HEK293T cells.

Results

We identifyde novomissense variants in the STK domain in 11 individuals, including two recurrent variants p.G510S (n=5) and p.G515S (n=3). All 11 individuals had Developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at < 2 years of age. All patients developed multiple seizures types, while 9/11 had seizures triggered by fever and 9/11 had drug-resistant seizures.In vitroanalysis of HEK293T cells transfected withMAST3cDNA carrying a subset of these patient-specific missense variants demonstrated variable but generally lower expression, with concomitant increased phosphorylation of the MAST3 target, ARPP-16, compared to wildtype. These findings suggest the patient-specific variants may confer MAST3 gain-of-function. Moreover, single-nuclei RNA sequencing and immunohistochemistry shows thatMAST3expression is restricted to excitatory neurons in the cortex late in prenatal development and postnatally.

Interpretation

In summary, we describeMAST3as a novel epilepsy-associated gene with a potential gain-of-function pathogenic mechanism that may be primarily restricted to excitatory neurons in the cortex.
Quantified Flu: an individual-centered approach to gaining sickness-related insights from wearable data
Authors: Tzovaras Bastian Greshake , Senabre Enric , Alexiou Karolina , Baldy Lukaz , Morane Basille , Bussod Ilona , Fribourg Melvin , Wac Katarzyna , Wolf Gary , Ball Mad
Published: March 2021

Background

Wearables have been used widely for monitoring health in general, and recent research results show that they can be used for predicting infections based on physiological symptoms. So far, the evidence has been generated in large, population-based settings. In contrast, the Quantified Self and Personal Science communities are composed of people interested in learning about themselves individually using their own data, often gathered via wearable devices.

Objective

We explore how a co-creation process involving a heterogeneous community of personal science practitioners can develop a collective self-tracking system to monitor symptoms of infection alongside wearable sensor data.

Methods

We engaged in a co-creation and design process with an existing community of personal science practitioners, jointly developing a working prototype of an online tool to perform symptom tracking. In addition to the iterative creation of the prototype (started on March 16, 2020), we performed a netnographic analysis, investigating the process of how this prototype was created in a decentralized and iterative fashion.

Results

The Quantified Flu prototype allows users to perform daily symptom reporting and is capable of visualizing those symptom reports on a timeline together with the resting heart rate, body temperature, and respiratory rate as measured by wearable devices. We observe a high level of engagement, with over half of the 92 users that engaged in the symptom tracking becoming regular users, reporting over three months of data each. Furthermore, our netnographic analysis highlights how the current Quantified Flu prototype is a result of an interactive and continuous co-creation process in which new prototype releases spark further discussions of features and vice versa.

Conclusions

As shown by the high level of user engagement and iterative development, an open co-creation process can be successfully used to develop a tool that is tailored to individual needs, decreasing dropout rates.
Therapeutic Anticoagulation in Critically Ill Patients with Covid-19 – Preliminary Report
Authors:   The REMAP-CAP,   ACTIV-4a,   ATTACC Investigators, Zarychanski Ryan
Published: March 2021

Background

Thrombosis may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic anticoagulation would improve outcomes in critically ill patients with Covid-19.

Methods

We conducted an open-label, adaptive, multiplatform, randomized, clinical trial. Patients with severe Covid-19, defined as the requirement for organ support with high flow nasal cannula, non-invasive ventilation, invasive ventilation, vasopressors, or inotropes, were randomized to receive therapeutic anticoagulation with heparin or pharmacological thromboprophylaxis as per local usual care. The primary outcome was an ordinal scale combining in-hospital mortality (assigned –1) and days free of organ support to day 21.

Results

Therapeutic anticoagulation met the pre-defined criteria for futility in patients with severe Covid-19. The primary outcome was available for 1,074 participants (529 randomized to therapeutic anticoagulation and 545 randomized to usual care pharmacological thromboprophylaxis). Median organ support-free days were 3 days (interquartile range –1, 16) in patients assigned to therapeutic anticoagulation and 5 days (interquartile range –1, 16) in patients assigned to usual care pharmacological thromboprophylaxis (adjusted odds ratio 0.87, 95% credible interval (CrI) 0.70-1.08, posterior probability of futility [odds ratio<1.2] 99.8%). Hospital survival was comparable between groups (64.3% vs. 65.3%, adjusted odds ratio 0.88, 95% CrI 0.67-1.16). Major bleeding occurred in 3.1% of patients assigned to therapeutic anticoagulation and 2.4% of patients assigned to usual care pharmacological thromboprophylaxis.

Conclusions

In patients with severe Covid-19, therapeutic anticoagulation did not improve hospital survival or days free of organ support compared to usual care pharmacological thromboprophylaxis.

Trial registration numbers NCT02735707, NCT04505774, NCT04359277, NCT04372589
A Software Solution for Clinical Protocol Management
Authors: Almeida João Rafael , Oliveira José Luís
Published: March 2021

Clinical treatments are mostly the result of consecutive success of medical procedures. The patterns in those procedures lead to creation of clinical guidelines which are currently essential to have better health treatments. The use of electronic health record systems (EHR) helps the patient management, but it fails in the treatment guidance due to the lack of clinical decision support systems. Although these systems have decision-making features incorporated, they are not designed for treatment management and guidance. In some top edge systems, this functionality was improved and integrated, but either they are tight to the typically complex EHR. Or, many times the independent solutions lack generality to support users and disease-specific protocols.

In this paper, we purpose a decision support web tool which works independently from EHR systems. This solution allows clinicians to build and manage rule-based clinical protocols, by facilitating health care treatments, reducing time, and increasing medication accuracy. Moreover, it also enables protocol sharing among distinct institutions and physicians, creating a larger database of clinical guidelines and a network of speciliased physicians in types of diseases.

The proposed system was evaluated with the implementation of distinct clinical protocols, from different medical fields. In this validation, we describe all the steps in the transformation of a clinical guideline, from the traditional format, into a ready-to-use protocol with guidance and recommendation features.

The purposed system was developed with the collaboration of health professionals from different Portuguese healthcare institutions, which helped in the identification of system requirements and gaps of the current systems.
Temporal Aspects of the Association between Exposure to the World Trade Center Disaster and Risk of Skin Melanoma
Authors: Boffetta Paolo , Goldfarb David G. , Zeig-Owens Rachel , Kristjansson Dana , Li Jiehui , Brackbill Robert M. , Farfel Mark R. , Cone James E. , Yung Janette , Kahn Amy R. , Qiao Baozhen , Schymura Maria J. , Webber Mayris P. , Prezant David J. , Dasaro Christopher R. , Todd Andrew C. , Hall Charles B.
Published: March 2021

Rescue/recovery workers who responded to the World Trade Center (WTC) attacks on 9/11/2001 were exposed to known/suspected carcinogens. Studies have identified an increased risk of skin melanoma in this population, but the temporal aspects of the association have not been investigated. A total of 44,540 non-Hispanic White workers from the WTC Combined Rescue/Recovery Cohort were observed between 3/12/2002 and 12/31/2015. Cancer data were obtained via linkages with 13 state registries. Poisson regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI), using the New York State population as reference; change points in the HRs were estimated using profile likelihood. We observed 247 incident cases of skin melanoma. No increase in incidence was detected between 2002 and 2004. Beginning in 2005, the HR was 1.34 (95% CI 1.18-1.52). A dose-response relationship was observed according to time worked on the WTC effort. Risk of melanoma among non-Hispanic White WTC rescue/recovery workers was elevated, beginning in 2005. While WTC-related exposure to ultraviolet radiation or other agents might have contributed to this result, exposures other than the WTC effort and enhanced medical surveillance cannot be discounted. Our results support the continued surveillance of this population for melanoma.
A tale of three SARS-CoV-2 variants with independently acquired P681H mutations in New York State
Authors: Lasek-Nesselquist Erica , Pata Janice , Schneider Erasmus , George Kirsten St.
Published: March 2021

Several SARS-CoV-2 variants of concern have independently acquired some of the same Spike protein mutations - notably E484K, N501Y, S477N, and K417T - associated with increased viral transmission and/or reduced sensitivity to neutralization by antibodies. Repeated evolution of the same mutations, particularly in variants that are now rapidly spreading in various regions of the world, suggests a fitness advantage. Mutations at position P681 in Spike – possibly affecting viral transmission - have also evolved multiple times, including in two variants of concern. Here, we describe three variants circulating in New York State that have independently acquired a P681H mutation and the different trajectories they have taken. While one variant rose to high prevalence since later summer 2020 it appears to be in decline. The other two variants were more recently detected in New York and harbor additional Spike mutations that might be cause for continued monitoring. The latter two P681H variants have shown moderate increases in prevalence but ultimately all might be subject to the same fate as more competitive variants come to dominate the scene.
Gene expression shapes the patterns of parallel evolution of herbicide resistance in the agricultural weedMonochoria vaginalis
Authors: Tanigaki Shinji , Uchino Akira , Okawa Shigenori , Miura Chikako , Hamamura Kenshiro , Matsuo Mitsuhiro , Yoshino Namiko , Ueno Naoya , Toyama Yusuke , Fukumi Naoya , Kijima Eiji , Masuda Taro , Shimono Yoshiko , Tominaga Tohru , Iwakami Satoshi
Published: March 2021

The evolution of herbicide resistance in weeds is an example of parallel evolution, through which genes encoding herbicide target proteins are repeatedly represented as evolutionary targets. The number of herbicide target-site genes differs among species, and little is known regarding the effects of duplicate gene copies on the evolution of herbicide resistance. We investigated the evolution of herbicide resistance inMonochoria vaginalis, which carries five copies of sulfonylurea target-site acetolactate synthase (ALS) genes. Suspected resistant populations collected across Japan were investigated for herbicide sensitivity andALSgene sequences, followed by functional characterisation andALSgene expression analysis. We identified over 60 resistant populations, all of which carried resistance-conferring amino acid substitutions exclusively inMvALS1orMvALS3. AllMvALS4alleles carried a loss-of-function mutation. Although the enzymatic properties of ALS encoded by these genes were not markedly different, the expression ofMvALS1andMvALS3was prominently higher among allALSgenes. The higher expression ofMvALS1andMvALS3is the driving force of the biased representation of genes during the evolution of herbicide resistance inM. vaginalis. Our findings highlight that gene expression is a key factor in creating evolutionary hotspots.
Beyond Turing:Far-from-equilibriumpatterns and mechano-chemical feedback
Authors: Veerman Frits , Mercker Moritz , Marciniak-Czochra Anna
Published: March 2021

Turing patterns are commonly understood as specific instabilities of a spatially homogeneous steady state, resulting from activator-inhibitor interaction destabilised by diffusion. We argue that this view is restrictive and its agreement with biological observations is problematic. We present two alternative to the ‘classical’ Turing analysis of patterns. First, we employ the abstract framework of evolution equations to enable the study offar-from-equilibriumpatterns. Second, we introduce a mechano-chemical model, with the surface on which the pattern forms being dynamic and playing an active role in the pattern formation, effectively replacing the inhibitor. We highlight the advantages of these two alternatives vis-à-vis the ‘classical’ Turing analysis, and give an overview of recent results and future challenges for both approaches.
Behavior emerges from unstructured muscle activity in response to neuromodulation
Authors: Elliott Amicia D. , Berndt Adama , Houpert Matthew , Roy Snehashis , Scott Robert L. , Chow Carson C. , Shroff Hari , White Benjamin H.
Published: March 2021

Identifying neural substrates of behavior requires defining actions in terms that map onto brain activity. Brain and muscle activity naturally correlate via the output of motor neurons, but apart from simple movements it has been difficult to define behavior in terms of muscle contractions. By mapping the musculature of the pupal fruit fly and comprehensively imaging muscle activation at single cell resolution, we here describe a multiphasic behavioral sequence inDrosophila. Our characterization identifies a previously undescribed behavioral phase and permits extraction of major movements by a convolutional neural network. We deconstruct movements into a syllabary of co-active muscles and identify specific syllables that are sensitive to neuromodulatory manipulations. We find that muscle activity shows considerable variability, which reduces upon neuromodulation. Our work provides a platform for studying whole-animal behavior, quantifying its variability across multiple spatiotemporal scales, and analyzing its neuromodulatory regulation at cellular resolution.
The dynamics of decision making and action during active sampling
Authors: Ozbagci Duygu , Moreno-Bote Ruben , Soto-Faraco Salvador
Published: March 2021

Embodied Cognition Theories (ECTs) propose that the decision process continues to unfold during the execution of choice actions, and its outcome manifests itself in these actions. Scenarios where actions not only express choice but also help sample information can provide a valuable test of this framework. Remarkably almost no studies so far have addressed this scenario. Here, we present a study testing just this paradigmatic situation with humans. On each trial, subjects categorized a central object image, blurred to different extents (2AFC task) by moving a cursor toward the left or right of the display. Upward cursor movements, orthogonal with respect to choice options, reduced the image blur and could be freely used to actively sample information. Thus, actions for decision and actions for sampling were made orthogonal to each other. We analyzed response trajectories to test a central prediction of ECTs; whether information-sampling movements co-occurred with the ongoing decision process. Trajectory data revealed were bimodally distributed, with one kind being direct towards one response option (non-sampling trials), and the other kind containing an initial upward component before veering off towards an option (sampling trials). This implies that there was an initial decision at the early stage of a trial whether to sample information or not. Importantly, the trajectories in sampling trials were not purely upward, but rather had a significant horizontal deviation that was visible early on in the movement. This result suggests that movements to sample information exhibit an online interaction with the decision process. The finding that decision processes interact with actions to sample information supports the ECT under novel, ecologically relevant constrains.
SeqWho: Reliable, rapid determination of sequence file identity usingk-mer frequencies
Authors: Bennett Christopher , Thornton Micah , Park Chanhee , Henry Gervaise , Zhang Yun , Malladi Venkat S. , Kim Daehwan
Published: March 2021

With the vast improvements in sequencing technologies and increased number of protocols, sequencing is finding more applications to answer complex biological problems. Thus, the amount of publicly available sequencing data has tremendously increased in repositories such as SRA, EGA, and ENCODE. With any large online database, there is a critical need to accurately document study metadata, such as the source protocol and organism. In some cases, this metadata may not be systematically verified by the hosting sites and may result in a negative influence on future studies. Here we present SeqWho, a program designed to heuristically assess the quality of sequencing files and reliably classify the organism and protocol type. This is done in an alignment-free algorithm that leverages a Random Forest classifier to learn from native biases ink-mer frequencies and repeat sequence identities between different sequencing technologies and species. Here, we show that our method can accurately and rapidly distinguish between human and mouse, nine different sequencing technologies, and both together, 98.32%, 97.86%, and 96.38% of the time in high confidence calls respectively. This demonstrates that SeqWho is a powerful method for reliably checking the identity of the sequencing files used in any pipeline and illustrates the program’s ability to leveragek-mer biases.
Single-cell transcriptome reveals a testis-specific expression profile ofTCEAin human spermatogenesis
Authors: Pankaew S. , Pramoj Na Ayutthaya P.
Published: March 2021

Transcription elongation factor A (TCEA) is a eukaryotic transcriptional molecule, required for a formation of initiation and elongation of gene transcription-mediated RNA polymerase II (RNAPII) complex, to promote transcription-coupled nucleotide excision repair (TC-NER) after RNAPII backtracking recovery.TCEAshares three isoforms in whichTCEA1is ubiquitously expressed among all eukaryotic cells. We found a spermatogenesisTCEA1andTCEA2expression profile has a unique transcriptional programme, compared with embryogenesis. Moreover, the testis-specificTCEA2profile correlates with gene transcription, whereasTCEA1specifically correlates with genes transcribed for Nuclear excision repair (NER) during human spermatogenesis. We also found that the expression activation ofRNF20, aTCEA1inhibitor, leads to expressionalTCEA1reduction, but having no direct impact onTCEA2expression, implying the potentialRNF20-dependent transcriptional switching ofTCEA2in transcriptional regulation during spermatogenesis. Our analysis defined a transcriptional bursting event where transcription-coupled repair (both Base excision repair and Nuclear excision repair) is a major pathway highly expressed in early spermatogenesis, supporting the transcriptional scanning hypothesis of which mutation of transcribed genes is effectively repaired as proposed by Xia B., et al. (2020).
Forced swim stress dynamically alters neural activity and bi-directionally modulates NMDA receptors in the prefrontal cortex
Authors: Parent Marc-Alexander L.T. , Lockridge Amber , Yuan Li-Lian
Published: March 2021

Repeated exposure to stress results in progressively divergent effects on cognitive behaviors that are dependent on the integrity of networks in the medial prefrontal cortex (mPFC). To investigate molecular mechanisms responsive to variable repetition of mild stress, we measured persistent neural activity,in vitro, from mPFC slices in mice that had been repetitively exposed to 10 minutes of forced swim stress for 3-10 days. 3-day short-term stress facilitated persistent neural activity by increasing event duration while 10 days suppressed event duration and amplitude. These dynamic changes were accompanied by a similar bi-directional modulation of the NMDA/AMPA receptor current ratio, an important synaptic mechanism for sustaining the persistency of neural activity. Specifically, short-term stress led to potentiated NMDA currents with slower decay kinetics, and extended stress produced smaller currents with faster decay. The inhibitory action of ifenprodil, a specific blocker of NR2B-containing NMDA receptors, was more effective in NMDA current suppression following light stress and less effective after longer stress compared to naive controls. Persistent activity and glutamate receptor balance in the neocortex have been linked to working memory and impulse control. Therefore, these results could provide insight for generating therapeutic strategies to prevent or reverse stress-induced cognitive deficits.
Normalization and De-noising of Single-cell Hi-C Data with BandNorm and 3DVI
Authors: Zheng Ye , Shen Siqi , Keleş Sündüz
Published: March 2021

Single-cell high-throughput chromatin conformation capture methodologies (scHi-C) enable profiling long-range genomic interactions at the single-cell resolution; however, data from these technologies are prone to technical noise and bias that, when unaccounted for, hinder downstream analysis. Here we developed a fast band normalization approach, BandNorm, and a deep generative modeling framework, 3DVI, to explicitly account for scHi-C specific technical biases. We present robust performances of BandNorm and 3DVI compared to existing state-of-the-art methods. BandNorm is effective in separating cell types, identification of interaction features, and recovery of cell-cell relationship, whereas de-noising by 3DVI successfully enables 3D compartments and domains recovery, especially for rare cell types.
Use of digital technology tools to examine patient adherence to a prescription omega-3 polyunsaturated acids therapy intended to mitigate cardiovascular risk: protocol and preliminary demographic data from the DIAPAsOn prospective observational study
Authors: Arutyunov Gregory P. , Arutyunov Alexander G. , Ageev Fail T. , Fofanova Tatiana V.
Published: March 2021

Sustained adherence and persistence with prescription medications is considered essential to achieve maximal treatment benefit for patients with major chronic non-communicable diseases such as hyperlipidemia and lipid-associated cardiovascular disease. It is widely documented, however, that a large percentage of patients with these conditions have poor longer-term compliance with their treatments. The population of Russia is affected by poor compliance in the same ways as populations elsewhere and continues to have high rates of cardiovascular disease.

Hypertriglyceridemia is suspected of contributing to residual cardiovascular risk in patients whose low-density lipoprotein cholesterol (LDL-C) is well controlled. A preparation of highly purified omega-3 polyunsaturated fatty acids (EPA/DHA=1.2/1-90%, marketed as OMACOR), is indicated for the control of high triglyceride levels and also for secondary prevention of myocardial infarction (MI).

DIAPAsON is a prospective observational program designed to evaluate the impact of digital technologies on patient compliance and adherence in a large sample of patients whose treatment scheme includes EPA/DHA=1.2/1-90%. A bespoke electronic data capture system has been developed for this purpose that enables information obtained during clinic visits to be supplemented by remote patient self-reporting. Other objectives of the program include raising patients’ awareness about their condition via educational materials available in patient personal accounts in the electronic system.

This report outlines the rationale and methodology of DIAPAsOn and the primary demographics of the study population.
A novel whole-blood stimulation assay to detect and quantify memory T-cells in COVID-19 patients
Authors: Mouton William , Compagnon Christelle , Saker Kahina , Daniel Soizic , Lacoux Xavier , Pozzetto Bruno , Oriol Guy , Djebali Sophia , Berthier Franck , Marvel Jacqueline , Walzer Thierry , Brengel-Pesce Karen , Trouiller-Assant Sophie
Published: March 2021

SARS-CoV-2 specific T-cells responses are essential for virus clearance. We present a novel and simple whole-blood assay allowing the detection of interferon-gamma-producing antiviral T-cells following peptide stimulation. We show that unlike neutralizing antibodies, antiviral memory T-cells persist at least 6 months in convalescent Covid-19 individuals.
Population based mean Vitamin D levels in 19 European Countries & COVID-19 Mortality
Authors: Ahmad Amar , Heumann Christian , Ali Raghib , Oliver Tim
Published: March 2021

Objectives

Reports early in the epidemic linking low mean national Vitamin D level with increased COVID-19 death, and until recently little research on the impact of Vitamin D deficiency on severity of COVID-19, led to this update of the initial report studying mortality up to the end of January 2021.

Design and Setting

Coronavirus pandemic data for 19 European countries were downloaded from Our World in Data, which was last updated on January 24, 2021. Data from March 21, 2020 to January 22, 2021 were included in the statistical analysis. Vitamin-D (25)-HD mean data were collected by literature review. Poisson mixed-effect model was used to model the data.

Results

European countries with Vitamin-D (25)-HD mean less than or equal to 50 have higher COVID-19 death rates as compared with European countries with Vitamin-D (25)-HD mean greater than 50, relative risk of 2.155 (95% CI: 1.068 – 4.347, p-value = 0.032). A statistically significant negative moderate Spearman rank correlation was observed between Vitamin-D (25)-HD mean and the number of COVID-19 deaths for each 14-day period during the COVID-19 pandemic time period.

Conclusions

The observation of the significantly lower COVID-19 mortality rates in countries with lowest annual sun exposure but highest mean Vitamin-D (25)-HD levels provides support for the use of food fortification. The need to consider re-configuring vaccine strategy due to emergence of large number of COVID-19 variants provides an opportunity to undertake such therapeutic randomized control trials.
Rationale and design of the Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) Trial and LIGHT-ACD Trial
Authors: Song Jiali , Wang Xiu-Ling , Wang Bin , Gao Yan , Liu Jia-Min , Zhang Hai-Bo , Li Xi , Li Jing , Wang Ji-Guang , Cai Jun , Herrin Jeph , Armitage Jane , Krumholz Harlan M. , Zheng Xin
Published: March 2021

Background

Computerized clinical decision support systems (CDSS) are low-cost, scalable tools with the potential to improve guideline-based antihypertensive treatment in primary care, but their effectiveness needs testing in pragmatic trials.

Methods

The Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) trial is a pragmatic, four-stage, cluster-randomized trial conducted in 94 primary care practices in China. For each city-based stage, practices are randomly assigned to either implementation of the CDSS for hypertension management (which guides physicians treatment recommendations based on measured blood pressure and patient characteristics), or usual care. Patients are enrolled during the first 3 months after site randomization and followed for 9 months. The primary outcome is the proportion of hypertension management visits at which guideline-based treatment is provided.

In a separate sub-study conducted within the CDSS, with the patient as the unit of randomization, the LIGHT-ACD trial, patients are randomized to receive different initial mono- or dual- antihypertensive therapy. The primary outcome of the LIGHT-ACD trial is the change in blood pressure from the first visit after site randomization to 9 months.

Discussion

The LIGHT trial will provide evidence on the effectiveness of a CDSS for improving guideline adherence for hypertension management in primary care in China. The sub-study, LIGHT-ACD trial, will provide data on the effect of different initial antihypertensive regimens for blood pressure management in this setting.

Trial registration

ClinicalTrials.gov, identifier: LIGHT (NCT03636334) and LIGHT-ACD (NCT03587103). Registered on 3 July 2018.