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Background: Researchers have a responsibility to protect all participants, especially vulnerable participants, from harm. Vulnerability is increasingly understood to be context specific, yet limited guidance is available regarding the vulnerability and agency of research participants in different cultural settings. This study aims to explore research participants' daily vulnerability and agency, and how these interact with participants' research experiences in their own words. Researchers' views and responses were also explored. Methods: A qualitative study was conducted around two scrub typhus research studies in northern Thailand. A thematic analysis was carried out on 42 semi-structured interviews with research participants, their families, researchers and key informants. Results: The majority of the research participants belonged to a hill tribe ethnic minority group. Common challenges were related to Thai language barriers, travel difficulties, uncertain legal status, unstable employment, lack of education and healthcare. We did not identify new vulnerabilities but we found that the extent of these vulnerabilities might be underestimated or even hidden from researchers in some cases. Despite these challenges people demonstrated agency in their daily lives and were often motivated and supported in this by family members. The majority of perceived research benefits were related to healthcare and gaining knowledge, while attending follow-up visits could be a burden for some. Conclusions: Our approach to research in culturally and socioeconomically diverse settings should be more responsive to participants' specific vulnerabilities and abilities evidenced in their daily life, rather than attributing vulnerability on the basis of membership of pre-defined 'vulnerable groups'. Researchers need to be aware and responsive towards the challenges participants face locally in order to minimise the burdens of research participation whilst allowing participants to benefit from research. [ABSTRACT FROM AUTHOR]

The inclusion of machine-learning-derived models in systematic reviews of risk prediction models for colorectal cancer is rare. Whilst such reviews have highlighted methodological issues and limited performance of the models included, it is unclear why machine-learning-derived models are absent and whether such models suffer similar methodological problems. This scoping review aims to identify machine-learning models, assess their methodology, and compare their performance with that found in previous reviews. A literature search of four databases was performed for colorectal cancer prediction and prognosis model publications that included at least one machine-learning model. A total of 14 publications were identified for inclusion in the scoping review. Data was extracted using an adapted CHARM checklist against which the models were benchmarked. The review found similar methodological problems with machine-learning models to that observed in systematic reviews for non-machine-learning models, although model performance was better. The inclusion of machine-learning models in systematic reviews is required, as they offer improved performance despite similar methodological omissions; however, to achieve this the methodological issues that affect many prediction models need to be addressed. [ABSTRACT FROM AUTHOR]

Global health practitioners and policymakers have become increasingly vocal about the complex challenges of identifying and quantifying the causes of death of the world's poorest people. To address this cause-of-death uncertainty and to minimise longstanding sensitivities about full autopsies, the Bill and Melinda Gates Foundation have been one of the foremost advocates of minimally invasive autopsy technology (MIA). MIA involves using biopsy needles to collect samples from key organs and body fluids; as such, it is touted as potentially more acceptable and less invasive than a complete autopsy, which requires opening the cadaver. In addition, MIA is considered a good means of collecting accurate bodily samples and can provide the crucial information needed to address cause-of-death uncertainty. In this paper, we employ qualitative data to demonstrate that while MIA technology has been introduced as a solution to the enduring cause-of-death uncertainty, the development and deployment of technologies such as these always constitute interventions in complex social and moral worlds; in this respect, they are both the solutions to and the causes of new kinds of uncertainties. We deconstruct the ways in which those new dimensions of uncertainty operate at different levels in the global health context. [ABSTRACT FROM AUTHOR]

Given the unprecedented scale of digital surveillance in the COVID-19 pandemic, designing and implementing digital technologies in ways that are equitable is critical now and in future epidemics and pandemics. Yet to date there has been very limited consideration about what is necessary to promote their equitable design and implementation. In this study, literature relating to the use of digital surveillance technologies during epidemics and pandemics was collected and thematically analyzed for ethical norms and concerns related to equity and social justice. Eleven norms are reported, including procedural fairness and inclusive approaches to design and implementation, designing to rectify or avoid exacerbating inequities, and fair access. Identified concerns relate to digital divides, stigma and discrimination, disparate risk of harm, and unfair design processes. We conclude by considering what dimensions of social justice the norms promote and whether identified concerns can be addressed by building the identified norms into technology design and implementation practice. [ABSTRACT FROM AUTHOR]

The cholesterol‐dependent cytolysins (CDCs) are a major family of bacterial pore‐forming proteins secreted as virulence factors by Gram‐positive bacterial species. CDCs are produced as soluble, monomeric proteins that bind specifically to cholesterol‐rich membranes, where they oligomerize into ring‐shaped pores of more than 30 monomers. Understanding the details of the steps the toxin undergoes in converting from monomer to a membrane‐spanning pore is a continuing challenge. In this review we summarize what we know about CDCs and highlight the remaining outstanding questions that require answers to obtain a complete picture of how these toxins kill cells. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary infection predominantly occurs via the nasal epithelium, but the nasal cell biology of SARS-CoV-2 is not well studied. We hypothesized that prophylactic intranasal administration of heparin may provide strain-agnostic protection for household contacts or those in high-risk settings against SARS-CoV-2 infection. Therefore, we investigated the ability of heparin to inhibit SARS-CoV-2 infection and replication in differentiated human nasal epithelial cells and showed that prolonged exposure to heparin inhibits virus infection. Furthermore, we establish a method for PCR detection of SARS-CoV-2 viral genomes in heparin-treated samples that can be adapted for the detection of viruses in clinical studies. [ABSTRACT FROM AUTHOR]

Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a life‐threatening birth defect that often occurs with other major birth defects (EA/TEF+). Despite advances in genetic testing, a molecular diagnosis can only be made in a minority of EA/TEF+ cases. Here, we analyzed clinical exome sequencing data and data from the DECIPHER database to determine the efficacy of exome sequencing in cases of EA/TEF+ and to identify phenotypic expansions involving EA/TEF. Among 67 individuals with EA/TEF+ referred for clinical exome sequencing, a definitive or probable diagnosis was made in 11 cases for an efficacy rate of 16% (11/67). This efficacy rate is significantly lower than that reported for other major birth defects, suggesting that polygenic, multifactorial, epigenetic, and/or environmental factors may play a particularly important role in EA/TEF pathogenesis. Our cohort included individuals with pathogenic or likely pathogenic variants that affect TCF4 and its downstream target NRXN1, and FANCA, FANCB, and FANCC, which are associated with Fanconi anemia. These cases, previously published case reports, and comparisons to other EA/TEF genes made using a machine learning algorithm, provide evidence in support of a potential pathogenic role for these genes in the development of EA/TEF. [ABSTRACT FROM AUTHOR]

We present a spectral analysis of two XMM–Newton observations of the narrow-line Seyfert 1 galaxy UGC 11763. UGC 11763 shows very different soft X-ray spectral shapes in the two observations separated by 12 yr. Three spectral models are considered to explain the multi-epoch X-ray variability of UGC 11763, one based on the relativistic disc reflection model, one based on multiple partially covering absorbers combined with the warm corona model, and a hybrid model. In the first model, the X-ray variability of UGC 11763 is caused by the emission from a compact coronal region with a variable size. The resulting disc reflection component changes accordingly. A warm absorption model with a modest column density is required in this model too. In the partially covering absorption scenario, the X-ray variability of UGC 11763 is caused by the variable covering factors of two absorbers located within a region of r < ≈100 r g. Moreover, the temperature and strength of the warm corona have to change significantly too to explain the variable underlying soft X-ray emission. Lastly, we investigate the possibility of variable intrinsic power-law emission from the hot corona combined with variable absorption in UGC 11763 without changing the geometry of the corona in the third model. This hybrid model provides a slightly better fit than the partially covering absorption model with improvements in fitting the iron emission band. Current CCD-resolution data cannot distinguish these spectral models for UGC 11763. Future high-resolution X-ray missions, e.g. Athena and XRISM , will test them by resolving different spectral components. [ABSTRACT FROM AUTHOR]

Faculty from academic, medical, state, and religious institutions presented workshops at a community and faith-based conference attended by seniors. Lifestyle changes and forms of spirituality were affirmed using a model of successful aging. Model has the potential to help unify the religious community around promoting successful aging. African American religious community provided critical leadership in achieving excellent participation rate. (JDM)

Explains the concept of positive spirituality and offers evidence that links positive spirituality with health. Describes effective partnerships between health professionals and religious communities and summarized the information as a basis for strengthening the existing successful aging model proposed by Rowe and Kahn. (Contains 59 references and 1 table.) (GCP)