bluuebunny/crossref_metadata_2025 huggingface dataset:
When Families Fail: Women’s Responses to Spousal Violence in Central Asia
Authors: Urbaeva Jildyz , Koo Jinhee , Childress Saltanat
Published: September 2021

Family violence is among the Grand Challenges for Social Work. Central Asian women report high rates of family violence, and yet they have limited options for responding to spousal violence. Despite the significance of the social problem, social workers are only beginning to develop interventions to address spousal violence in Central Asia. Authors used the domestic violence module from the 2012 Demographic and Health Surveys conducted in Kyrgyzstan and Tajikistan for analysis of spousal dynamics and women’s responses to spousal violence. Dependent variables were help seeking, physical retaliation against husband, and divorce from husband, and independent variables were severe mixed violence, injuries, and fear. Authors applied latent class analysis for identifying types of violence experienced by women. Logistic regression was used to measure associations between variables. Authors utilized bootstrapping percentile confidence intervals for assessing the indirect effects of severe violence via injuries and fear. Severe mixed violence and injuries were related to an increased likelihood of a woman’s response, while fear of husband reduced the likelihood of physical retaliation and divorce. Results suggest a strong need for social work interventions.
Perceptions, Knowledge, and Attitudes about Human Trafficking Questionnaire: Extending Its Utility with Social Work Students
Authors: Welch-Brewer Chiquitia , Nsonwu Maura , Busch-Armendariz Noël , Heffron Laurie Cook
Published: September 2021

This study, a two-site, cross-sectional survey of university students (n = 321 at site 1; n = 201 at site 2), extends the development and utility of the Perceptions, Knowledge, and Attitudes about Human Trafficking Questionnaire by generating factor-based scales and scores to represent values for its three factors (Self-Appraisal of Knowledge/Skills, Worldview of Human Trafficking, and Help-Seeking Behavior/Personal Beliefs) in order to examine their relationship to background criterion variables and assess differences between social work and non–social work students and between subgroups of social work students. Across both samples, the background variables of human trafficking training and professional responsibilities related to addressing human trafficking were predictive of self-appraisal of knowledge/skills. Additionally, social work students had higher scores than non–social work students on the worldview of human trafficking and help-seeking behavior/personal beliefs factor-based scales, suggesting that social work students perceived human trafficking to be more of a social problem and held fewer misperceptions of the help-seeking behavior of and a greater willingness to provide social services to persons who are trafficked than non–social work students. Implications for social work education, practice, and research are presented.
2Visual Culture
Authors: Lewis India
Published: September 2021

This chapter addresses books published in the field of visual culture in 2020, and is divided into three sections: 1. Curatorial Practice; 2. Thinking About Space; and 3. The New Craft. The books under review cover a range of subjects within their specialities but reflect general trends in contemporary writing and study in the field of visual culture. The first section looks at publications that examine curatorial practice (In the Meantime: Speculations on Art, Curation, and Exhibitions, by Jens Hoffman; Museums Inside Out: Artist Collaborations and New Exhibition Ecologies by Mark W. Rectanus); the second section examines books that describe theories of space (Architecture and Ekphrasis: Space, Time and the Embodied Description of the Past by Dana Arnold; Construction Site for Possible Worlds, edited by Amanda Beech and Robin Mackay); and the third and final section examines publications about craft and its ethics (The New Politics of the Handmade: Craft, Art and Design, edited by Anthea Black and Nicole Burisch).
Associations Among Nurses' Mental/Physical Health, Lifestyle Behaviors, Shift Length, and Workplace Wellness Support During COVID-19
Authors: Melnyk Bernadette Mazurek , Hsieh Andreanna Pavan , Tan Alai , Teall Alice M. , Weberg Dan , Jun Jin , Gawlik Kate , Hoying Jacqueline
Published: September 2021

Work cultures supportive of wellness and shorter shift length have been associated with better mental/physical health outcomes in nurses, but how the coronavirus disease-19 (COVID-19) pandemic impacted such outcomes is not known. This study's aims were to (1) describe the mental/physical health, well-being, and healthy lifestyle behaviors of nurses during the pandemic; (2) explore the pandemic's impact on their health and healthy lifestyle behaviors; and (3) determine the associations of perceived workplace wellness support and shift length with nurses' health, well-being, and healthy lifestyle behaviors. A cross-sectional descriptive design was used with 264 nurses associated with Trusted Health. Nurses completed a survey containing valid and reliable scales measuring depression, anxiety, burnout and quality of life, perceived wellness culture, and healthy lifestyle behaviors. Results indicated that more than 50% of nurses had worsening mental/physical health relating to the pandemic. Compared with nurses whose workplaces provided little/no wellness support, nurses with workplaces that supported their wellness were 3 to 9 times as likely to have better mental/physical health, no/little stress, no burnout, and high quality of life. Nurses who worked longer shifts had poorer health outcomes. These findings indicate that workplace wellness support and shorter shifts positively impacted nurse mental/physical health and professional quality of life amidst the pandemic.
Impact of Pediatric Primary Palliative Care Education and Mentoring in Practice
Authors: Lafond Deborah , Perko Kathy , Fisher Deborah , Mahmood Laila A. , Hinds Pamela S.
Published: September 2021

Primary palliative care education and mentoring strengthens frontline clinicians' confidence and competence in pediatric palliative care, and potentially mitigates their moral distress. The project aims were to improve the knowledge, attitudes, and skills of frontline intradisciplinary clinicians in caring for children with serious conditions and their families. We undertook an intensive educational initiative consisting of didactic and mentoring sessions, and mentored quality improvement projects. Outcomes included the following: 93.3% of participants reported comfort in discussing death, suffering, spirituality, and hope with families, and increased comfort in end-of-life care (89.5%), increased knowledge (94.7%) and skills (100%), improved communication (100%), and being better prepared to discuss and access palliative care resources (100%). Secondary outcomes included 33% increase in specialty pediatric palliative care consults and 98% increase in the integration of specialty palliative care for patients with high-risk cancers. Specialty pediatric palliative care referral became standard for patients with cystic fibrosis, high-risk solid and brain tumors, heart failure, and patients receiving a stem cell transplant. Clinician self-reported moral distress decreased by 30%. This project improved primary palliative care knowledge, attitudes, and confidence in skills, access to care, and family satisfaction, and decreased clinician self-reported moral distress. We report on the 4-year period of project implementation and sustainability.
Expressing Gratitude for Transitions, for Relationships, and for the Hope They Bring
Authors: Sweeney Cynthia Divens
Published: September 2021

The past 18 months has been filled with transitions for healthcare organizations, for nurses, and for the patients and families they care for. As we transition from the real and virtual confines inflicted by the pandemic, the light shines on gratitude for relationships cultivated and the hope they bring.
A novel anti-influenza combined therapy assessed by single cell RNA-sequencing
Authors: Medaglia Chiara , Kolpakov Ilya , Zhu Yong , Constant Samuel , Huang Song , Zwygart Arnaud Charles-Antoine , Cagno Valeria , Dermitzakis Emmanouil T. , Stellacci Francesco , Xenarios Ioannis , Tapparel Caroline
Published: September 2021

Influenza makes millions of people ill every year, placing a large burden on the healthcare system and the economy. To develop a novel treatment against influenza, we combined virucidal sialylated cyclodextrins with interferon lambda and demonstrated, in human airway epithelia, that the two compounds inhibit the replication of a clinical H1N1 strain more efficiently when administered together rather than alone. We investigated the mechanism of action of the combined treatment by single cell RNA sequencing analysis and found that both the single and combined treatments impair viral replication to different extents across distinct epithelial cell types. We also showed that each cell type comprises multiple sub-types, whose proportions are altered by H1N1 infection, and assess the ability of the treatments to restore them. To the best of our knowledge this is the first study investigating the effectiveness of an antiviral therapy by transcriptomic studies at the single cell level.
Inflammation and nitro-oxidative stress in current suicidal attempts and current suicidal ideation: a systematic review and meta-analysis
Authors: Vasupanrajit Asara , Jirakran Ketsupar , Tunvirachaisakul Chavit , Solmi Marco , Maes Michael
Published: September 2021

A meta-analysis showed a significant association between activated immune-inflammatory and nitro-oxidative (IO&NS) pathways and suicide attempts (SA). There is no data on whether suicidal ideation (SI) is accompanied by activated IO&NS pathways and whether there are differences between SA and SI. The current study searched PubMed, Google Scholar, and Web of Science, for articles published from inception until May 10, 2021, and systematically reviewed and meta-analyzed the association between recent SA/SI (< 3 months) and IO&NS biomarkers. We included studies which compared psychiatric patients with and without SA and SI and controls (either healthy controls or patients without SA or SI) and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence intervals (CI). Our search included 59 studies comprising 4.034 SA/SI cases and 12.377 controls. Patients with SA/SI showed activated IO&NS pathways (SMD: 0.299; CI: 0.200; 0.397) when compared to controls. The immune profiles were more strongly associated with SA than with SI, particularly when compared to healthy controls, as evidenced by activated IO&NS (SMD: 0.796; CI: 0.503; 1.089), immune (SMD: 1.409; CI: 0.637; 1.462), inflammatory (SMD: 1.200; CI: 0.584; 1.816), and neurotoxic (SMD: 0.904; CI: 0.431; 1.378) pathways. The effects sizes of the IO&NS, immune and inflammatory profiles were significantly greater in SA than in SI. In conclusion: increased neurotoxicity due to inflammation and nitro-oxidative stress and lowered neuroprotection explains at least in part why psychiatric patients show increased SA and SI. The IO&NS pathways are more pronounced in recent SA than in SI.
Convergent antibody responses associated with broad neutralization of hepatitis C virus and clearance of infection
Authors: Skinner Nicole E. , Ogega Clinton O. , Frumento Nicole , Clark Kaitlyn E. , Yegnasubramanian Srinivasan , Cox Andrea L. , Crowe James E. , Ray Stuart C. , Bailey Justin R.
Published: September 2021

Early development of broadly neutralizing antibodies (bNAbs) targeting the hepatitis C virus (HCV) envelope glycoprotein E2 is associated with spontaneous clearance of infection, so induction of bNAbs is a major goal of HCV vaccine development. However, much remains to be learned at a molecular level about protective E2-reactive antibodies, since HCV infection persists in some individuals despite early development of broadly neutralizing plasma. To examine B cell repertoire features associated with broad neutralization and viral clearance, we performed RNA sequencing of the B cell receptors (BCRs) of HCV E2-reactive B cells of people with cleared or persistent HCV, including subjects with high or low plasma neutralizing breadth in both clearance and persistence groups. We identified many E2-reactive public BCR clonotypes, which are antibody clones with the same V and J-genes and identical CDR3 sequences, shared among subjects grouped by either clearance or neutralization status. The majority (89) of these public clonotypes were shared by two subjects with broad plasma neutralizing activity and cleared infection, but not found in subjects with high plasma neutralizing breadth and persistent infection. We cloned a potent, cross-reactive neutralizing monoclonal antibody (mAb) by pairing the most abundant public heavy and light chains from these two subjects, providing evidence that broadly E2-reactive public clonotypes arise in a subset of individuals with broadly neutralizing plasma and spontaneous clearance of infection. Further characterization of the molecular features and function of these antibodies can inform HCV vaccine development.
Clinical Results with a B Cell Activating Anti-CD73 Antibody for the Immunotherapy of COVID-19
Authors: Miller Richard A. , Guru Pramod , Bauer Philippe , Robles Jorge , Tomaszewski Christian , Overcash J. Scott , Waters Michael , Cameron Miriam , Olalla Sierra Julián , Mashhedi Haider , Mobasher Mehrdad , Janc James , Rudnick Jenny A. , Hu Shenshen , Jones William B. , Kwei Long , Mahabhashyam Suresh , Willingham Stephen B. , Criner Gerard
Published: September 2021

Robust polyclonal humoral immune responses have the potential to generate a diverse set of antibodies to neutralize and eliminate viruses such as SARS-CoV-2 and protect against transmission, re-infection and the evolution of variants that evade immunity. CD73 is present on subsets of human B and T cells where it plays a role in lymphocyte activation and migration. CD73 also functions as an ectoenzyme that converts AMP into immunosuppressive adenosine. We have developed a humanized anti-CD73 antibody, mupadolimab (CPI-006), that blocks CD73 enzymatic activity and activates CD73POSB cells, thereby inducing differentiation into plasmablasts, immunoglobulin class switching, and antibody secretion independent of the adenosine modulatory activity. These effects suggest mupadolimab may enhance the magnitude, diversity, and duration of anti-viral responses in patients with COVID-19. This hypothesis was tested in a dose escalation phase 1 trial in 29 hospitalized patients with COVID-19. Single doses of 0.3 mg/kg – 5 mg/kg mupadolimab were well tolerated with no drug related adverse events. Doses greater than 0.3 mg/kg resulted in rapid generation of IgG and IgM to SARS-CoV-2 significantly above titers measured in convalescent controls, with elevated IgG titers sustained for more than 6 months beyond presentation of symptoms. Based on these findings, a randomized double-blind, placebo-controlled Phase 3 study in hospitalized patients was initiated. The primary endpoint was proportion of patients alive and free from respiratory failure within 28 days. This trial was discontinued early during the period of waning COVID-19 incidence after enrolling 40 patients. Although underpowered, results from this trial suggest improvement in the primary and key secondary endpoints in patients treated with single doses of 2 mg/kg and 1 mg/kg compared to placebo. The presumed mechanism of action, stimulation of B cells, may represent a novel approach to immunotherapy of COVID-19 and other viral infections.
Predictors of COVID-19 vaccine uptake in healthcare workers: a cross-sectional study in Greece
Authors: Galanis Petros , Moisoglou Ioannis , Vraka Irene , Siskou Olga , Konstantakopoulou Olympia , Katsiroumpa Aglaia , Kaitelidou Daphne
Published: September 2021

Background

The role of healthcare workers (HCWs) in the general public health is crucial and their decision to vaccinate against the COVID-19 can have a positive impact on the general population facilitating widespread COVID-19 vaccine uptake.

Objective

To estimate the uptake of a COVID-19 vaccine in HCWs and to expand our knowledge regarding the predictors of COVID-19 vaccine uptake.

Methods

An on-line cross-sectional study was conducted in Greece during August 2021. We collected socio-demographic data of HCWs and we measured attitudes towards vaccination and COVID-19, knowledge and trust. We used a convenience sample since we distributed the questionnaire through social media and e-mails.

Results

Study population included 855 HCWs. The majority of HCWs were vaccinated against the COVID-19 (91.5%). According to multivariate analysis, females, HCWs without a previous COVID-19 diagnosis, and HCWs with previous seasonal influenza vaccination history had a greater probability to take a COVID-19 vaccine. Also, increased self-perceived knowledge regarding COVID-19 and increased trust in COVID-19 vaccines and government regarding the information about the COVID-19 vaccines were associated with COVID-19 vaccine uptake. On the other hand, HCWs with more concerns about the side-effects of COVID-19 vaccination were more reluctant to take a COVID-19 vaccine.

Conclusions

Our study provides a timely assessment of COVID-19 vaccination status among HCWs and identifies specific factors associated with COVID-19 vaccine uptake. By understanding these factors, policy makers and scientists will be able to develop novel strategies to improve COVID-19 vaccine uptake among HCWs.
An Integrated Molecular Atlas of Alzheimer’s Disease
Authors: Wörheide Maria A. , Krumsiek Jan , Nataf Serge , Nho Kwangsik , Greenwood Anna K. , Wu Tong , Huynh Kevin , Weinisch Patrick , Römisch-Margl Werner , Lehner Nick ,   The AMP-AD Consortium,   The Alzheimer’s Disease Neuroimaging Initiative,   The Alzheimer’s Disease Metabolomics Consortium, Baumbach Jan , Meikle Peter J. , Saykin Andrew J. , Murali Doraiswamy P. , van Duijn Cornelia , Suhre Karsten , Kaddurah-Daouk Rima , Kastenmüller Gabi , Arnold Matthias
Published: September 2021

INTRODUCTION

Embedding single-omics disease associations into the wider context of multi-level molecular changes in Alzheimer’s disease (AD) remains one central challenge in AD research.

METHODS

Results from numerous AD-specific omics studies from AMP-AD, NIAGADS, and other initiatives were integrated into a comprehensive network resource and complemented with molecular associations from large-scale population-based studies to provide a global view on AD.

RESULTS

We present the AD Atlas, an online resource (www.adatlas.org) integrating over 20 large studies providing disease-relevant information on 20,353 protein-coding genes, 8,615 proteins, 997 metabolites and 31 AD-related phenotypes. Multiple showcases demonstrate the utility of this resource for contextualization of AD research results and subsequent downstream analyses, such as drug repositioning approaches.

DISCUSSION

By providing a global view on multi-omics results through a user-friendly interface, the AD Atlas enables the formulation of molecular hypotheses and retrieval of clinically relevant insights that can be validated in follow-up analyses or experiments.
Hydroxychloroquine inhibits proteolytic processing of endogenous TLR7 protein in human primary plasmacytoid dendritic cells
Authors: Cenac Claire , Ducatez Mariette , Guéry Jean-Charles
Published: September 2021

Toll-like receptor 7 (TLR7) triggers antiviral immune responses through its capacity to recognize single-stranded RNA. Proteolytic cleavage of TLR7 protein is required for its functional maturation in the endosomal compartment. Structural studies demonstrated that the N- and C-terminal domains of TLR7 are connected and involved in ligand binding after cleavage. Hydroxychloroquine (HCQ), an antimalarial drug, has been studied for its antiviral effects. HCQ increases pH in acidic organelles and has been reported to potently inhibit endosomal TLR activation. Whether HCQ can prevent endogenous TLR7 cleavage in primary immune cells, such as plasmacytoid dendritic cells (pDCs), had never been examined. Here, using a validated anti-TLR7 antibody suitable for biochemical detection of native TLR7 protein, we show that HCQ-treatment of fresh PBMCs, CAL-1 leukemic and primary human pDCs inhibits TLR7 cleavage and results in accumulation of full-length protein. As a consequence, we observe an inhibition of pDC activation in response to TLR7 stimulation with synthetic ligands and viruses including inactivated SARS-CoV2, which we show herein activates pDCs through TLR7-signaling. Together, our finding suggests that the major pathway by which HCQ inhibits ssRNA-sensing by pDCs may rely on its capacity to inhibit endosomal acidification and the functional maturation of TLR7 protein.
Hemoglobin levels among male agricultural workers: analyses from the Demographic and Health Surveys to investigate a marker for chronic kidney disease of uncertain etiology
Authors: Lin Yuzhou , Heng Siyu , Anand Shuchi , Deshpande Sameer K. , Small Dylan S.
Published: September 2021

Background

Chronic kidney disease of uncertain etiology (CKDu) has been found at high frequency in several lowland agricultural areas. Whether CKDu occurs in other countries with large agricultural populations remains uncertain, primarily due to lack of systematic data on kidney function. Hemoglobin (Hgb) levels are an ancillary marker for kidney dysfunction. We estimate the causal effect of agricultural work on Hgb level in men. A causal effect may indicate the presence of CKDu.

Methods

We use Demographic and Health Surveys (DHS) data from seven African and Asian countries to estimate the causal effect of agricultural work on altitude-adjusted Hgb levels after adjusting for seven measured confounders. To assess potential bias due to unmeasured socioeconomic differences, we use multiple control groups that differ in non-agricultural occupation. We conduct sensitivity analyses to assess the robustness of our causal conclusions to unmeasured confounding.

Results

Data were available for 41,180 agricultural workers and 55,705 non-agricultural workers. On average, Hgb levels were 0.09 g/dL lower among agricultural workers compared to matched controls. Significant effects were observed in Ethiopia, India, Lesotho, and Senegal, with effects from 0.07 to 0.30 g/dL lower hemoglobin among agricultural workers.

Conclusions

We find evidence that men engaged in agricultural work in four of the seven countries studied have modestly lower Hgb levels compared with comparable men. Since underlying kidney disease could be a potential explanation for this finding, our data support consideration to integrating kidney function assessments within DHS surveys and other population-based surveys.
Investigating the impact of weakly supervised data on text mining models of publication transparency: a case study on randomized controlled trials
Authors: Hoang Linh , Jiang Lan , Kilicoglu Halil
Published: September 2021

Lack of large quantities of annotated data is a major barrier in developing effective text mining models of biomedical literature. In this study, we explored weak supervision strategies to improve the accuracy of text classification models developed for assessing methodological transparency of randomized controlled trial (RCT) publications. Specifically, we used Snorkel, a framework to programmatically build training sets, and UMLS-EDA, a data augmentation method that leverages a small number of existing examples to generate new training instances, for weak supervision and assessed their effect on a BioBERT-based text classification model proposed for the task in previous work. Performance improvements due to weak supervision were limited and were surpassed by gains from hyperparameter tuning. Our analysis suggests that refinements to the weak supervision strategies to better deal with multi-label case could be beneficial.
Medication Management at Home and Medication Adherence in Older Patients with Polypharmacy: In-Depth Interviews with Home Visits
Authors: Vatcharavongvan Pasitpon , Puttawanchai Viwat
Published: September 2021

Background

Older patients with multiple non-communicable diseases (NCDs) usually require ≥5 concurrent medications or polypharmacy. Medication adherence is the main concern in these patients. Medication management at home may play an important role in medication adherence; yet, unlike other factors, the topic has not been well examined.

Objective

This study aims to explore how medication management at home affects medication adherence qualitatively.

Methods

We conducted home visits and in-depth interviews with 19 patients aged ≥60 years with polypharmacy and took photos of medication storage locations. Transcripts were analyzed using thematic content analysis.

Results

Of the 19 patients (mean age=69 years), nine reported good medication adherence. Two themes emerged: medication management at home and factors affecting medication adherence. Medication management at home comprised three subthemes: a medication storage system, a medication sorting system, and remaining medications. Some patients with medication nonadherence removed medications from blister packages. Other factors affecting medication adherence included knowledge, attitude, and lifestyles. All the patients had a positive attitude towards medication adherence; however, misunderstanding about medication administration prevented them from adhering to medications.

Conclusion

Medication management at home for the elderly with polypharmacy affected medication adherence. Health professionals should explore how patients manage medications at home and their knowledge about medication administration to improve medication adherence.

Key messages

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Older patients had their own medication management system.

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Removing medications from blister packages was associated with medication nonadherence.

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Unintentional medication nonadherence was common in older patients engaging in outdoor activities.
Vaccine effectiveness and duration of protection of Comirnaty, Vaxzevria and Spikevax against mild and severe COVID-19 in the UK
Authors: Andrews Nick , Tessier Elise , Stowe Julia , Gower Charlotte , Kirsebom Freja , Simmons Ruth , Gallagher Eileen , Chand Meera , Brown Kevin , Ladhani Shamez N , Ramsay Mary , Bernal Jamie Lopez
Published: September 2021

Background

COVID-19 vaccines have been used for 9 months in the UK. Real world data have demonstrated the vaccines to be highly effective against COVID-19, severe disease and death. Here, we estimate vaccine effectiveness over time since the second dose of Comirnaty, Vaxzevria and Spikevax in England.

Methods

We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease, hospitalisation and mortality by age, comorbidity status and over time after the second dose to investigate waning separately for Alpha and Delta variants.

Results

Vaccine effectiveness against symptomatic disease peaked in the early weeks after the second dose and then fell to 47.3 (95% CI 45 to 49.6) and 69.7 (95% CI 68.7 to 70.5) by 20+ weeks against the Delta variant for Vaxzevria and Comirnaty, respectively. Waning of vaccine effectiveness was greater for 65+ year-olds compared to 40-64 year-olds. Vaccine effectiveness fell less against hospitalisations to 77.0 (70.3 to 82.3) and 92.7 (90.3 to 94.6) beyond 20 weeks post-vaccination and 78.7 (95% CI 52.7 to 90.4) and 90.4 (95% CI 85.1 to 93.8) against death for Vaxzevria and Comirnaty, respectively. Greater waning was observed among 65+ year-olds in a clinically extremely vulnerable group and 40-64-year olds with underlying medical conditions compared to healthy adults.

Conclusions

We observed limited waning in vaccine effectiveness against hospitalisation and death more than 20 weeks post-vaccination with Vaxzevria or Comirnaty. Waning was greater in older adults and those in a clinical risk group, suggesting that these individuals should be prioritised for booster doses.
Effect of Pre-Exercise Caffeine Intake on Endurance Performance and Core Temperature Regulation During Exercise in the Heat: A Systematic Review with Meta-Analysis
Authors: Naulleau Catherine , Jeker David , Pancrate Timothée , Claveau Pascale , Deshayes Thomas A. , Burke Louise M. , Goulet Eric D.B.
Published: September 2021

Background

Heat is associated with physiological strain and endurance performance (EP) impairments. Studies have investigated the impact of caffeine intake upon EP and core temperature (CT) in the heat, but results are conflicting. There is a need to systematically determine the impact of pre-exercise caffeine intake in the heat.

Objective

Use a meta-analytical approach to determine the effect of pre-exercise caffeine intake on EP and CTin the heat.

Design

Systematic review with meta-analysis.

Data sources

Four databases and cross-referencing.

Data analysis

Weighted mean effect summaries using random-effects models for EP and CT, as well as meta regressions with robust standard errors to explore confounders.

Study selection

Placebo-controlled, randomized studies in adults (≥ 18 yrs old) with caffeine intake at least 30 min before endurance exercise ≥ 30 min, performed in ambient conditions ≥ 27°C.

Results

Respectively 6 and 12 studies examined caffeine’s impact on EP and CT, representing 52 and 205 endurance-trained individuals. On average, 6 mg/kg body mass of caffeine were taken 1 h before exercises of ∼ 70 min conducted at 34°C and 47% relative humidity. Caffeine supplementation improved EP by 2.0 ± 0.7% (95% CI: 0.6 to 3.5%) and increased the rate of change in CTby 0.10 ± 0.04°C/h (95% CI: 0.03 to 0.16°C/h), compared with the ingestion of a placebo.

Conclusion

Caffeine ingestion of 6 mg/kg body mass ∼ 1 h before an exercise in the heat provides a worthwhile improvement in EP of 2%, while trivially increasing the rate of change in CTby 0.10°C/h.
Modeling the systemic risks of COVID-19 on the wildland firefighting workforce
Authors: Belval Erin J , Bayham Jude , Thompson Matthew P , Dilliott Jacob , Buchwald Andrea G.
Published: September 2021

Wildfire management in the US relies on a complex nationwide network of shared resources that are allocated based on regional need. While this network bolsters firefighting capacity, it may also provide pathways for COVID-19 transmission between fire sites. We develop an agent-based model of COVID-19 built on historical wildland fire assignments using detailed dispatch data from 2016-2018, which form a network of firefighters dispersed spatially and temporally across the US. We use this model to simulate SARS-CoV-2 transmission under several intervention scenarios including vaccination and social distancing. We find vaccination and social distancing are effective at reducing transmission at fire incidents. Under a scenario assuming High Compliance with recommended mitigations (including vaccination), infection rates, number of outbreaks, and worker days missed are effectively negligible. Under a contrasting Low Compliance scenario, it is possible for cascading outbreaks to emerge leading to relatively high numbers of worker days missed. The current set of interventions in place successfully mitigate the risk of cascading infections between fires, and off-assignment infection may be the dominant infection concern in the 2021 season. COVID-19 control measures in place in wildfire management are highly beneficial at decreasing both the health and resource impacts of the ongoing pandemic.
A meta-analysis of the genome-wide association studies on two genetically correlated phenotypes (self-reported headache and self-reported migraine) identifies four new risk loci for headaches (N=397,385)
Authors: Meng Weihua , Reel Parminder S , Nangia Charvi , Rajendrakumar Aravind Lathika , Hebert Harry L , Adams Mark J , Zheng Hua , Lu Zen Haut ,   23andMe Research Team, Ray Debashree , Colvin Lesley A , Palmer Colin NA , McIntosh Andrew , Smith Blair H
Published: September 2021

Headache is one of the commonest complaints that doctors need to address in clinical settings. The genetic mechanisms of different types of headache are not well understood. In this study, we performed a meta-analysis of genome-wide association studies (GWAS) on the self-reported headache phenotype from the UK Biobank cohort and the self-reported migraine phenotype from the 23andMe resource using the metaUSAT for genetically correlated phenotypes (N=397,385). We identified 38 loci for headaches, of which 34 loci have been reported before and 4 loci were newly identified. The LRP1-STAT6-SDR9C7 region in chromosome 12 was the most significantly associated locus with a leading P value of 1.24 × 10−62 of rs11172113. The ONECUT2 gene locus in chromosome 18 was the strongest signal among the 4 new loci with a P value of 1.29 × 10−9 of rs673939. Our study demonstrated that the genetically correlated phenotypes of self-reported headache and self-reported migraine can be meta-analysed together in theory and in practice to boost study power to identify more new variants for headaches. This study has paved way for a large GWAS meta-analysis study involving cohorts of different, though genetically correlated headache phenotypes.
Absence of Excess Mortality in a Highly Vaccinated Population During the Initial Covid-19 Delta Period
Authors: Faust Jeremy Samuel , Du Chengan , Mayes Katherine Dickerson , Renton Benjamin , Li Shu-Xia , Lin Zhenqiu , Krumholz Harlan M.
Published: September 2021

Background

All-cause excess mortality (the number of deaths that exceed projections in any period) has been widely reported during the Covid-19 pandemic. Whether excess mortality has occurred during the Delta wave is less well understood.

Methods

We performed an observational study using data from the Massachusetts Department of Health. Five years of US Census population data and CDC mortality statistics were applied to a seasonal autoregressive integrated moving average (sARIMA) model to project the number of expected deaths for each week of the pandemic period, including the Delta period (starting in June 2021, extending through August 28th 2021, for which mortality data are >99% complete). Weekly Covid-19 cases, Covid-19-attributed deaths, and all-cause deaths are reported. County-level excess mortality during the vaccine campaign are also reported, with weekly rates of vaccination in each county that reported 100 or more all-cause deaths during any week included in the study period.

Results

All-cause mortality was not observed after March 2021, by which time over 75% of persons over 65 years of age in Massachusetts had received a vaccination. Fewer deaths than expected (which we term ‘deficit mortality’) occurred both during the summer of 2020, the spring of 2021 and during the Delta wave (beginning June 13, 2021 when Delta isolates represented >10% of sequenced cases). After the initial wave in the spring of 2020, more Covid-19-attributed deaths were recorded that all-cause excess deaths, implying that Covid-19 was misattributed as the underlying cause, rather than a contributing cause of death in some cases.

Conclusion

In a state with high vaccination rates, excess mortality has not been recorded during the Delta period. Deficit mortality has been recorded during this period.
Impact of prior SARS-CoV-2 infection on post-vaccination SARS-CoV-2 spike IgG antibodies in a longitudinal cohort of healthcare workers
Authors: Zhong Diana , Xiao Shaoming , Debes Amanda K. , Egbert Emily R. , Caturegli Patrizio , Colantuoni Elizabeth , Milstone Aaron M.
Published: September 2021

Waning serum antibodies against SARS-CoV-2 have sparked discussions about long-term immunity and need for vaccine boosters. We examined SARS-CoV-2 spike IgG antibodies in a longitudinal cohort, comparing antibody decay in individuals who received an mRNA SARS-CoV-2 vaccine, with and without prior SARS-CoV-2 infection. We completed a longitudinal cohort of healthcare workers (HWs) between June 2020 and September 2021. HWs were included if they had a serum sample collected after SARS-CoV-2 infection and/or a serum sample collected ≥ 14 days after second dose of an mRNA SARS-CoV-2 vaccine. Linear regression models adjusting for vaccine type, age, and sex were used to compare post-vaccination antibody levels between 1) HWs with and without prior SARS-CoV-2 infection and 2) HWs with prior SARS-CoV-2 infection ≤ 90 days and > 90 days prior to first vaccine. Serum was collected from 98 HWs after SARS-CoV-2 infection and before vaccine, and 1960 HWs ≥ 14 days following second vaccine dose. Serum spike antibody levels were higher after vaccination than after natural infection. Compared to SARS-CoV-2 naïve individuals, those with prior infection maintained higher post-vaccination mean spike IgG values at 1, 3, and 6 months, after adjusting for age, sex, and vaccine type. Individuals with PCR-confirmed infection > 90 days before vaccination had higher post-vaccination antibody levels than individuals infected ≤ 90 days before vaccination. Individuals with three exposures to spike protein maintain the highest antibody levels particularly when first and second exposures were greater than 90 days apart. A booster dose provides a third exposure and may similarly induce a more durable antibody response.
Face mask fit modifications that improve source control performance
Authors: Blachere Francoise M. , Lemons Angela R. , Coyle Jayme P. , Derk Raymond C. , Lindsley William G. , Beezhold Donald H. , Woodfork Karen , Duling Matthew G. , Boutin Brenda , Boots Theresa , Harris James R. , Nurkiewicz Tim , Noti John D.
Published: September 2021

BACKGROUND

During the COVID-19 pandemic, face masks are used as source control devices to reduce the expulsion of respiratory aerosols from infected people. Modifications such as mask braces, earloop straps, knotting and tucking, and double masking have been proposed to improve mask fit. However, the data on source control are limited.

METHODS

The effectiveness of mask fit modifications was determined by conducting fit tests on human subjects and simulator manikins and by performing simulated coughs and exhalations using a source control measurement system.

RESULTS

Medical masks without modification blocked ≥56% of cough aerosols and ≥42% of exhaled aerosols. Modifying fit by crossing the earloops or placing a bracket under the mask did not increase performance, while using earloop toggles, an earloop strap, and knotting and tucking the mask increased performance. The most effective modifications for improving source control performance were double masking and using a mask brace. Placing a cloth mask over a medical mask blocked ≥85% of cough aerosols and ≥91% of exhaled aerosols. Placing a brace over a medical mask blocked ≥95% of cough aerosols and ≥99% of exhaled aerosols.

CONCLUSION

Fit modifications can greatly improve the performance of face masks as source control devices for respiratory aerosols.
How complete is the reporting of somatic sensory training interventions in individuals following a stroke? Protocol for a systematic review
Authors: Feller Daniel , Pedri Caterina , Gozzer Paolo , Innocenti Tiziano , Trentin Francesca
Published: September 2021

Background

To implement intervention from research to clinical practice, treatments must be adequately described in randomized clinical trials. Specific reporting guidelines, such as the TIDieR checklist, have been developed to enhance the reporting of intervention in clinical trials.

Objective

We aim to evaluate the adherence to the TIDieR checklist in randomized controlled trials evaluating somatic sensory training interventions in individuals following a stroke.

Material and Methods

We will perform a systematic review of the literature, searching PubMed, CENTRAL, and PEDro for randomized controlled trials that evaluate the efficacy of any rehabilitative intervention on somatic sensation in patients with a history of stroke, independently form the comparator.

Two authors independently will evaluate the completeness of the reporting of the intervention using the TIDieR checklist.

A descriptive analysis of the total score and the individual items of the TIDieR will be produced.

Ethics and dissemination

A manuscript with results will be submitted for publication in a peer-reviewed journal in the rehabilitation field.
Identification and classification of cis-regulatory elements in the amphipod crustacean Parhyale hawaiensis
Authors: Sun Dennis A , Bredeson Jessen V , Bruce Heather S , Patel Nipam H
Published: September 2021

Emerging research organisms enable the study of biology that cannot be addressed using classical “model” organisms. The development of new data resources can accelerate research in such animals. Here, we present new functional genomic resources for the amphipod crustacean Parhyale hawaiensis, facilitating the exploration of gene regulatory evolution using this emerging research organism. We use Omni-ATAC-Seq, an improved form of the Assay for Transposase-Accessible Chromatin coupled with next-generation sequencing (ATAC-Seq), to identify accessible chromatin genome-wide across a broad time course of Parhyale embryonic development. This time course encompasses many major morphological events, including segmentation, body regionalization, gut morphogenesis, and limb development. In addition, we use short- and long-read RNA-Seq to generate an improved Parhyale genome annotation, enabling deeper classification of identified regulatory elements. We discover differential accessibility, predict nucleosome positioning, infer transcription factor binding, cluster peaks based on accessibility dynamics, classify biological functions, and correlate gene expression with accessibility. Using a Minos transposase reporter system, we demonstrate the potential to identify novel regulatory elements using this approach, including distal regulatory elements. This work provides a platform for the identification of novel developmental regulatory elements in Parhyale, and offers a framework for performing such experiments in other emerging research organisms.

Primary Findings

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Omni-ATAC-Seq identifies cis-regulatory elements genome-wide during crustacean embryogenesis

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Combined short- and long-read RNA-Seq improves the Parhyale genome annotation

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ImpulseDE2 analysis identifies dynamically regulated candidate regulatory elements

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NucleoATAC and HINT-ATAC enable inference of nucleosome occupancy and transcription factor binding

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Fuzzy clustering reveals peaks with distinct accessibility and chromatin dynamics

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Integration of accessibility and gene expression reveals possible enhancers and repressors

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Omni-ATAC can identify known and novel regulatory elements
A flexible electronic strain sensor for the real-time monitoring of tumor progression
Authors: Abramson Alex , Chan Carmel T. , Khan Yasser , Mermin-Bunnell Alana , Matsuhisa Naoji , Fong Robyn , Shad Rohan , Hiesinger William , Mallick Parag , Gambhir Sanjiv Sam , Bao Zhenan
Published: September 2021

Healthcare professionals and scientists utilize tumor shrinkage as a key metric to establish the efficacy of cancer treatments. However, current measurement tools such as CT scanners and calipers only provide brief snapshots of the dynamic geometric changes occurring in vivo, and they are unable to characterize the continuous micrometer-scale volumetric transformations transpiring at minute timescales. Here we present a stretchable electronic strain sensor, with a 10-micron scale resolution, capable of continuously monitoring tumor volume progression in real-time. In mouse models with subcutaneously implanted lung cancer or B-cell lymphoma tumors our sensors discerned a significant change in the tumor volumes of treated mice within 5 hours after small molecule therapy or immunotherapy initiation. Histology, caliper measurements, and luminescence imaging over a one-week treatment period validated the data from the continuous sensor. We anticipate that real-time tumor progression datasets could help expedite and automate the process of screening cancer therapies in vivo.
Epilepsy-causing KCNT1 variants increase KNa1.1 channel activity by disrupting the activation gate
Authors: Cole Bethan A. , Pilati Nadia , Lippiat Jonathan D.
Published: September 2021

Gain-of-function pathogenic missense KCNT1 variants are associated with several developmental and epileptic encephalopathies (DEE). With few exceptions, patients are heterozygous and there is a paucity of mechanistic information about how pathogenic variants increase KNa1.1 channel activity and the behaviour of heterotetrameric channels comprising both wild-type (WT) and variant subunits. To better understand these, we selected a range of variants across the DEE spectrum, involving mutations in different protein domains and studied their functional properties. Whole-cell electrophysiology was used to characterise homomeric and heteromeric KNa1.1 channel assemblies carrying DEE-causing variants in the presence and absence of 10 mM intracellular sodium. Voltage-dependent activation of homomeric variant KNa1.1 assemblies were more hyperpolarised than WT KNa1.1 and, unlike WT KNa1.1, exhibited voltage-dependent activation in the absence of intracellular sodium. Heteromeric channels formed by co-expression of WT and variant KNa1.1 had activation kinetics intermediate of homomeric WT and variant KNa1.1 channels, with residual sodium-independent activity. In general, WT and variant KNa1.1 activation followed a single exponential, with time constants unaffected by voltage or sodium. Mutating the threonine in the KNa1.1 selectivity filter disrupted voltage-dependent activation, but sodium-dependence remained intact. Our findings suggest that KNa1.1 gating involves a sodium-dependent activation gate that modulates a voltage-dependent selectivity filter gate. Collectively, all DEE-associated KNa1.1 mutations lowered the energetic barrier for sodium-dependent activation, but some also had direct effects on selectivity filter gating. Destabilisation of the inactivated unliganded channel conformation can explain how DEE-causing amino acid substitutions in diverse regions of the channel structure all cause gain-of-function.