The BabySaver: Design of a New Device for Neonatal Resuscitation at Birth with Intact Placental Circulation.

The initial bedside care of premature babies with an intact cord has been shown to reduce mortality; there is evidence that resuscitation of term babies with an intact cord may also improve outcomes. This process has been facilitated by the development of bedside resuscitation surfaces. These new devices are unaffordable, however, in most of sub-Saharan Africa, where 42% of the world's 2.4 million annual newborn deaths occur. This paper describes the rationale and design of BabySaver, an innovative low-cost mobile resuscitation unit, which was developed iteratively over five years in a collaboration between the Sanyu Africa Research Institute (SAfRI) in Uganda and the University of Liverpool in the UK. The final BabySaver design comprises two compartments; a tray to provide a firm resuscitation surface, and a base to store resuscitation equipment. The design was formed while considering contextual factors, using the views of individual women from the community served by the local hospitals, medical staff, and skilled birth attendants in both Uganda and the UK.

Structural under-reporting of informed consent, data handling and sharing, ethical approval, and application of Open Science principles as proxies for study quality conduct in COVID-19 research: a systematic scoping review.

BACKGROUND: The COVID-19 pandemic required science to provide answers rapidly to combat the outbreak. Hence, the reproducibility and quality of conducting research may have been threatened, particularly regarding privacy and data protection, in varying ways around the globe. The objective was to investigate aspects of reporting informed consent and data handling as proxies for study quality conduct. METHODS: A systematic scoping review was performed by searching PubMed and Embase. The search was performed on November 8th, 2020. Studies with hospitalised patients diagnosed with COVID-19 over 18 years old were eligible for inclusion. With a focus on informed consent, data were extracted on the study design, prestudy protocol registration, ethical approval, data anonymisation, data sharing and data transfer as proxies for study quality. For reasons of comparison, data regarding country income level, study location and journal impact factor were also collected. RESULTS: 972 studies were included. 21.3% of studies reported informed consent, 42.6% reported waivers of consent, 31.4% did not report consent information and 4.7% mentioned other types of consent. Informed consent reporting was highest in clinical trials (94.6%) and lowest in retrospective cohort studies (15.0%). The reporting of consent versus no consent did not differ significantly by journal impact factor (p=0.159). 16.8% of studies reported a prestudy protocol registration or design. Ethical approval was described in 90.9% of studies. Information on anonymisation was provided in 17.0% of studies. In 257 multicentre studies, 1.2% reported on data sharing agreements, and none reported on Findable, Accessible, Interoperable and Reusable data principles. 1.2% reported on open data. Consent was most often reported in the Middle East (42.4%) and least often in North America (4.7%). Only one report originated from a low-income country. DISCUSSION: Informed consent and aspects of data handling and sharing were under-reported in publications concerning COVID-19 and differed between countries, which strains study quality conduct when in dire need of answers.

Work fatigue during COVID-19 lockdown teleworking: the role of psychosocial, environmental, and social working conditions.

Background: During national lockdowns in response to the COVID-19 pandemic, previously office-based workers who transitioned to home-based teleworking faced additional demands (e.g., childcare, inadequate homeworking spaces) likely resulting in poor work privacy fit. Previous office research suggests poor work privacy fit is associated with lower wellbeing and higher work fatigue. Emerging evidence suggests a relationship between childcare duties during pandemic teleworking and work fatigue. In addition to psychosocial working conditions (job demand, job control, and job change management), which are acknowledged predictors of work fatigue, this poses a significant threat to occupational health during pandemic teleworking. However, the relative effects of aspects of the psychosocial environment (job demands and resources), the home office environment (including privacy fit), and the social environment (childcare) on work fatigue as well as their interactions are under-explored. Objective: This study examined the relationships between the psychosocial, environmental, and social working conditions of teleworking during the first COVID-19 lockdown and work fatigue. Specifically, the study examined teleworkers' physical work environment (e.g., if and how home office space is shared, crowding, and noise perceptions) as predictors of privacy fit and the relationship between privacy fit, childcare, psychosocial working conditions (job demand, job control, and job change management), and work fatigue. Work privacy fit was hypothesized to mediate the relationship between childcare and work fatigue. Methods: An online cross-sectional survey was conducted with teleworkers (n = 300) during the first COVID-19 lockdown in April and May 2020; most participants were in Germany, Switzerland, and the United Kingdom. Results: Path analysis was used to examine the hypothesized relationships. Privacy fit was lower for those reporting greater levels of noise in home-working spaces and those feeling crowded at home. Work fatigue was lower amongst those with greater privacy fit and higher amongst those with high levels of job demand. An indirect relationship was observed between childcare and work fatigue with privacy fit mediating this relationship. Conclusion: The influence of privacy fit has so far been largely neglected in research on teleworking, especially during the pandemic. However, its contribution to workers' wellbeing should be acknowledged in occupational health strategies.

Sustainable urban mobility: Flexible bus service network design in the post-pandemic era.

The excessive traffic congestion in vehicles lowers the service quality of urban bus system, reduces the social distance of bus passengers, and thus, increases the spread speed of epidemics, such as coronavirus disease. In the post-pandemic era, it is one of the main concerns for the transportation agency to provide a sustainable urban bus service to balance the travel convenience in accessibility and the travel safety in social distance for bus passengers, which essentially reduces the in-vehicle passenger congestion or smooths the boarding-alighting unbalance of passengers. Incorporating the route choice behavior of passengers, this paper proposes a sustainable service network design strategy by selecting one subset of the stops to maximize the total passenger-distance (person × kilometers) with exogenously given loading factor and stop-spacing level, which can be captured by constrained non-linear programming model. The loading factor directly determines the in-vehicle social distance, and the stop-spacing level can efficiently reduce the ridership with short journey distance. Therefore, the sustainable service network design can be used to help the government minimize the spread of the virus while guaranteeing the service quality of transport patterns in the post-pandemic era. A real-world case study is adopted to illustrate the validity of the proposed scheme and model.

QSAR and molecular docking studies on designing potent inhibitors of SARS-CoVs main protease.

Background: Severe acute respiratory syndrome coronavirus (SARS-CoVs) have emerged as a global health threat, which had caused a high rate of mortality. There is an urgent need to find effective drugs against these viruses. Objective: This study aims to predict the activity of unsymmetrical aromatic disulfides by constructing a QSAR model, and to design new compounds according to the structural and physicochemical attributes responsible for higher activity towards SARS-CoVs main protease. Methods: All molecules were constructed in ChemOffice software and molecular descriptors were calculated by CODESSA software. A regression-based linear heuristic method was established by changing descriptors datasets and calculating predicted IC50 values of compounds. Then, some new compounds were designed according to molecular descriptors from the heuristic method model. The compounds with predicted values smaller than a set point were constantly screened out. Finally, the properties analysis and molecular docking were conducted to further understand the structure-activity relationships of these finalized compounds. Results: The heuristic method explored the various descriptors responsible for bioactivity and gained the best linear model with R2 0.87. The success of the model fully passed the testing set validation, proving that the model has both high statistical significance and excellent predictive ability. A total of 5 compounds with ideal predicted IC50 were found from the 96 newly designed derivatives and their properties analyze was carried out. Molecular docking experiments were conducted for the optimal compound 31a, which has the best compound activity with good target protein binding capability. Conclusion: The heuristic method was quite reliable for predicting IC50 values of unsymmetrical aromatic disulfides. The present research provides meaningful guidance for further exploration of the highly active inhibitors for SARS-CoVs.

Experiences of Sex Workers in Chicago during COVID-19: A Qualitative Study.

COVID-19 exacerbated health disparities, financial insecurity, and occupational safety for many within marginalized populations. This study, which took place between 2019 and 2022, aimed to explore the way in which sex workers (n = 36) in Chicago were impacted by COVID-19. We analyzed the transcripts of 36 individual interviews with a diverse group of sex workers using thematic analysis. Five general themes emerged regarding the detrimental impact of COVID-19 on sex workers: (1) the impact of COVID-19 on physical health; (2) the economic impact of COVID-19; (3) the impact of COVID-19 on safety; (4) the impact of COVID-19 on mental health; and (5) adaptive strategies for working during COVID-19. Participants reported that their physical and mental health, economic stability, and safety worsened due to COVID-19 and that adaptive strategies did not serve to improve working conditions. Findings highlight the ways in which sex workers are particularly vulnerable during a public health crisis, such as COVID-19. In response to these findings, targeted resources, an increased access to funding, community-empowered interventions and policy changes are needed to protect the health and safety of sex workers in Chicago.

An optimized thermodynamics integration protocol for identifying beneficial mutations in antibody design.

Accurate identification of beneficial mutations is central to antibody design. Many knowledge-based (KB) computational approaches have been developed to predict beneficial mutations, but their accuracy leaves room for improvement. Thermodynamic integration (TI) is an alchemical free energy algorithm that offers an alternative technique for identifying beneficial mutations, but its performance has not been evaluated. In this study, we developed an efficient TI protocol with high accuracy for predicting binding free energy changes of antibody mutations. The improved TI method outperforms KB methods at identifying both beneficial and deleterious mutations. We observed that KB methods have higher accuracies in predicting deleterious mutations than beneficial mutations. A pipeline using KB methods to efficiently exclude deleterious mutations and TI to accurately identify beneficial mutations was developed for high-throughput mutation scanning. The pipeline was applied to optimize the binding affinity of a broadly sarbecovirus neutralizing antibody 10-40 against the circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant. Three identified beneficial mutations show strong synergy and improve both binding affinity and neutralization potency of antibody 10-40. Molecular dynamics simulation revealed that the three mutations improve the binding affinity of antibody 10-40 through the stabilization of an altered binding mode with increased polar and hydrophobic interactions. Above all, this study presents an accurate and efficient TI-based approach for optimizing antibodies and other biomolecules.

Recent Advances in Covalent Drug Discovery.

In spite of the increasing number of biologics license applications, the development of covalent inhibitors is still a growing field within drug discovery. The successful approval of some covalent protein kinase inhibitors, such as ibrutinib (BTK covalent inhibitor) and dacomitinib (EGFR covalent inhibitor), and the very recent discovery of covalent inhibitors for viral proteases, such as boceprevir, narlaprevir, and nirmatrelvir, represent a new milestone in covalent drug development. Generally, the formation of covalent bonds that target proteins can offer drugs diverse advantages in terms of target selectivity, drug resistance, and administration concentration. The most important factor for covalent inhibitors is the electrophile (warhead), which dictates selectivity, reactivity, and the type of protein binding (i.e., reversible or irreversible) and can be modified/optimized through rational designs. Furthermore, covalent inhibitors are becoming more and more common in proteolysis, targeting chimeras (PROTACs) for degrading proteins, including those that are currently considered to be 'undruggable'. The aim of this review is to highlight the current state of covalent inhibitor development, including a short historical overview and some examples of applications of PROTAC technologies and treatment of the SARS-CoV-2 virus.

In Silico Structure-Based Vaccine Design.

Structure-based vaccine design (SBVD) is an important technique in computational vaccine design that uses structural information on a targeted protein to design novel vaccine candidates. This increasing ability to rapidly model structural information on proteins and antibodies has provided the scientific community with many new vaccine targets and novel opportunities for future vaccine discovery. This chapter provides a comprehensive overview of the status of in silico SBVD and discusses the current challenges and limitations. Key strategies in the field of SBVD are exemplified by a case study on design of COVID-19 vaccines targeting SARS-CoV-2 spike protein.

Toward user-centered assistive technologies for aging in place with cognitive impairment: a survey.

PURPOSE: To reduce the burden of Alzheimer's disease, the use of assistive technologies for patients and their informal caregivers is considered essential. However, these technologies are made as "one size fits all" instead of being tailored to accommodate people with varying degrees of cognitive impairment and those with diverse races/ethnicities. Thus, the aim of this survey was to determine whether the types of assistance needed most, and the technology used by those with cognitive impairment differed by race (White/non-Hispanics, Black or African Americans, and Hispanic/Latinos or Puerto Ricans) and severity of dementia (mild, moderate, severe). RESEARCH DESIGN AND METHODS: One hundred and eighty informal caregivers of people with different levels of severity of cognitive impairment and several different races/ethnicities filled out an online survey regarding assistance needed and technologies used. RESULTS: The results show that racial minorities considered the needs for assistance with Basic Activities of Daily Living as more important compared to White/non-Hispanics with mild dementia. Furthermore, Hispanic/Latinos or Puerto Ricans and White/non-Hispanics with severe dementia were shown to use technology that is designed to help with Instrumental Activities of Daily Living more than those with moderate dementia. Lastly, during COVID-19, devices to assist with walking, preparing meals and personal hygiene have been used significantly more by White/non-Hispanics with severe dementia compared to Hispanic/Latinos or Puerto Ricans. CONCLUSION: The results point to the need to design for those with severe dementia, regardless of race, and should focus on addressing needs related to both Instrumental and Basic Activities of Daily Living.

Developers of assistive technology should consider designing technology that can accommodate all severity levels of cognitive impairment.More research is needed to determine the usability of assistive technology that is designed for those with cognitive impairments.

The Longitudinal and Vertical Integration of Health Systems Science in an Undergraduate Medical Education Program: A Means to Support "Curricular Elasticity".

Although health systems science (HSS) has become increasingly included as requisite curricular content in undergraduate medical education (UME), educators have many implementation options for integrating HSS content into medical school training. Learning from medical schools' authentic experiences and lessons learned for the successful and sustainable implementation of HSS would be valuable. We share our experience with the longitudinal and vertical integration of HSS at the Sidney Kimmel Medical College (SKMC) at Thomas Jefferson University in Philadelphia over the past six years. We posit that our approach to curricular design has afforded us the "curricular elasticity" needed to keep our educational program current and flexible in the rapidly changing healthcare and geopolitical landscape.

Implementation of a brief online skills group of dialectical behaviour therapy for emotional dysregulation in Latinx: a withdrawal experimental single-case design.

BACKGROUND: Dialectical behaviour therapy (DBT) skills groups have shown promise as an effective treatment for clients with emotional dysregulation, especially when combined with individual DBT. However, their efficacy is not well established as an online therapy, or in the Latinx population. AIMS: This study aimed to explore satisfaction, retention and effects of an internet-based DBT group added to individual online sessions. METHOD: An ABAB withdrawal experimental single-case design was conducted to evaluate the effect of a brief online DBT skills group on emotional dysregulation, anxiety and depression for five Latinx participants. DBT skills group (phase B) were compared with placebo group sessions (phase A) and fortnightly individual DBT sessions were offered throughout to manage risk. RESULTS: Visual inspection showed a decrease in level of emotional dysregulation and a large effect size according to the Nonoverlap of All Pairs when comparing group DBT and placebo phases. Although depression symptoms decreased after introducing group DBT, anxiety indicators decreased most during the second round of group placebo sessions. DISCUSSION: Whilst only a pilot, this study suggests that online group DBT in Latinx populations is feasible and effective for changing emotional regulation processes but may not effectively target anxiety. Future research might increase the number of DBT sessions in order to enhance learning opportunities and generalization. Replication with larger sample sizes and diverse modalities is needed.

Antimicrobial Peptides: Challenging Journey to the Pharmaceutical, Biomedical, and Cosmeceutical Use.

Antimicrobial peptides (AMPs), or host defence peptides, are short proteins in various life forms. Here we discuss AMPs, which may become a promising substitute or adjuvant in pharmaceutical, biomedical, and cosmeceutical uses. Their pharmacological potential has been investigated intensively, especially as antibacterial and antifungal drugs and as promising antiviral and anticancer agents. AMPs exhibit many properties, and some of these have attracted the attention of the cosmetic industry. AMPs are being developed as novel antibiotics to combat multidrug-resistant pathogens and as potential treatments for various diseases, including cancer, inflammatory disorders, and viral infections. In biomedicine, AMPs are being developed as wound-healing agents because they promote cell growth and tissue repair. The immunomodulatory effects of AMPs could be helpful in the treatment of autoimmune diseases. In the cosmeceutical industry, AMPs are being investigated as potential ingredients in skincare products due to their antioxidant properties (anti-ageing effects) and antibacterial activity, which allows the killing of bacteria that contribute to acne and other skin conditions. The promising benefits of AMPs make them a thrilling area of research, and studies are underway to overcome obstacles and fully harness their therapeutic potential. This review presents the structure, mechanisms of action, possible applications, production methods, and market for AMPs.

'It feels smaller now': The impact of the COVID-19 lockdown on apartment residents and their living environment - A longitudinal study.

Introduction: The COVID-19 pandemic and associated lockdown restrictions prolonged residents' exposure to their home environment. The impact of lockdowns could be heightened for apartment residents as they typically have smaller, less versatile homes, and share communal and circulation spaces. This study examined changes in apartment residents' perceptions and experiences of their dwelling before and after the Australian COVID-19 national lockdown. Methods: Participants consisted of 214 Australian adults who completed a survey on apartment living between 2017 and 2019 and a follow-up survey in 2020. Questions focused on residents' perceptions of their dwelling design, apartment living experiences, and personal life events/changes due to the pandemic. Differences between pre- and post-lockdown periods were assessed via paired sample t-tests. The lived experience of a subset of residents (n = 91) following lockdown was also assessed using qualitative content analysis of free-text responses to an open-ended survey item. Results: Compared to the pre-pandemic period, after the lockdown residents reported less satisfaction with the amount/layout of their apartment space and private open space (e.g., balconies or courtyards). Increased noise annoyance from indoor and outdoor noise sources was also reported, however disputes with neighbours decreased. The qualitative content analysis highlighted a complex interplay of personal, social and environmental impacts of the pandemic on residents. Conclusions: Findings suggest an increased 'dose' of the apartment facilitated by stay-at-home orders negatively influenced residents' apartment perceptions. Design strategies that maximise spacious, flexible dwelling layouts with health-promoting elements (e.g., enhanced natural light/ventilation and private open space) are recommended to promote healthy and restorative living environments for apartment residents.

Adaptations to a cohort study in response to the COVID-19 pandemic: insights from Growing Up in Ireland.

Growing Up in Ireland (GUI) is the national longitudinal study of children and young people in the Republic of Ireland and has followed two cohorts for over ten years to date: Cohort '98 who were recruited into the study at age nine years and Cohort '08, recruited at age nine months. The study aims to describe the lives of Irish children and young people in terms of their development, with a view to positively affecting policies and services available for them. Traditionally, data collection involved in-home visits from an interviewer who conducted face-to-face interviews, recorded physical measurements of study participants and administered cognitive assessments. However, with the onset of the COVID-19 pandemic and the associated restrictions, significant adaptations were required to these methods to ensure data collection for the pilot and main fieldwork for Cohort '08 at age 13 could continue to the expected timeline. Face-to-face interviews with participants were replaced with telephone and web-based modes, interviewer training was conducted online, online resources were made available for interviewers and participants and COVID-19 related items were added to questionnaires. In addition to the scheduled data collection, a special COVID-19 survey was also conducted on both GUI cohorts in December 2020 to explore the impact of the pandemic on participants' lives. This paper outlines the adaptations made to traditional data collection methods in GUI, highlighting the challenges that were met, but also the benefits of some changes that may be worth incorporating into future waves of GUI.

Heart failure after dengue infection- a population-based self-controlled case-series study.

BACKGROUND: Major cardiovascular events (MACEs) have been described with dengue infection. Among these MACEs, heart failure (HF) is the most common but has not been thoroughly assessed. This study aimed to evaluate the association between dengue and HF. METHODS: Under the self-controlled case-series study design, we used the Notifiable Infectious Disease dataset linkage with the National Health Insurance claims data to obtain the study subjects. All laboratory-confirmed dengue cases who were hospitalized for HF after dengue infection within one year between 2009 and 2015 in Taiwan were included. We identified the first 7 and 14 days after dengue infection as the risk intervals. The incidence rate ratio (IRR) and 95% confidence interval (CI) for HF were estimated by conditional Poisson regression. RESULTS: Among the 65,906 dengue patients, 230 had admission for HF after dengue infection within one year. The IRR of HF admission within the first week after dengue infection was 56.50 (95% C.I. 43.88-72.75). This risk was highest in >60 years (IRR = 59.32, 95% C.I. 45.43-77.43) and lower in 0-40 years (IRR = 25.82, 95% C.I. 2.89-231.02). The risk was nearly nine times higher among admission (for dengue infection) than among nonadmission cases (IRR 75.35 vs. 8.61, p < 0.0001). The risks increased slightly in the second week 8.55 and became less obvious after the third and fourth week. CONCLUSIONS: Patients with dengue infection have a risk of developing acute heart failure within one week, especially in >60 years, men, and dengue admission subjects. The findings emphasize the awareness of diagnosis and further appropriate treatment of HF.

From tech to tact: emotion dysregulation in online communication during the COVID-19 pandemic.

Recent theorizing argues that online communication technologies provide powerful, although precarious, means of emotional regulation. We develop this understanding further. Drawing on subjective reports collected during periods of imposed social restrictions under COVID-19, we focus on how this precarity is a source of emotional dysregulation. We make our case by organizing responses into five distinct but intersecting dimensions wherein the precarity of this regulation is most relevant: infrastructure, functional use, mindful design (individual and social), and digital tact. Analyzing these reports, along with examples of mediating technologies (i.e., self-view) and common interactive dynamics (e.g., gaze coordination), we tease out how breakdowns along these dimensions are sources of affective dysregulation. We argue that the adequacy of available technological resources and competencies of various kinds matter greatly to the types of emotional experiences one is likely to have online. Further research into online communication technologies as modulators of both our individual and collective well-being is urgently needed, especially as the echoes of the digital push that COVID-19 initiated are set to continue reverberating into the future.