Vogeloconnor0740

Bladder cancer is the most common malignant tumour of the urinary system that is characterised by significant intra-tumoural heterogeneity. While large-scale sequencing projects have provided a preliminary understanding of tumour heterogeneity, these findings are based on the average signals obtained from the pooled populations of diverse cells. Recent advances in single-cell sequencing (SCS) technologies have been critical in this regard, opening up new ways of understanding the nuanced tumour biology by identifying distinct cellular subpopulations, dissecting the tumour microenvironment, and characterizing cellular genomic mutations. By integrating these novel insights, SCS technologies are expected to make powerful and meaningful changes to the current diagnosis and treatment of bladder cancer through the identification and usage of novel biomarkers as well as targeted therapeutics. SCS can discriminate complex heterogeneity in a large population of tumour cells and determine the key molecular properties that influence clinical outcomes. Here, we review the advances in single-cell technologies and discuss their applications in cancer research and clinical practice, with a specific focus on bladder cancer.

The coronavirus disease-2019 (COVID-19) pandemic and accompanying lockdown restrictions impacted social life significantly. We studied associations of sociodemographic factors, mental and social health markers, and brain structure with social health trajectories during the COVID-19 pandemic.

Prospective longitudinal population-based cohort study.

Community-dwelling inhabitants of Rotterdam, the Netherlands.

Repeated questionnaires including questions on social health were sent to Rotterdam Study participants from April 2020 onwards. Social health data at study baseline were available for 5017 participants (mean age 68.7 ± 11.3; 56.9% women).

Determinants were assessed in routine Rotterdam Study follow-up (1990-2020), including global brain volumes in a subset of participants (N = 1720). We applied linear mixed models and generalized estimating equations to quantify associations between determinants and trajectories of loneliness, perceived social isolation and social connectedness over three time poss and social isolation alongside stable social connectedness over time during the pandemic. Social health is multidimensional, especially during a global health crisis.A 6-year-old boy, born with hypoplastic left heart syndrome, underwent total cavopulmonary connection and later presented in a significantly deteriorated condition. A CT scan revealed multiple thrombi in the extracardiac conduit, although the patient was maintained on an effective anticoagulant therapy. Further examination revealed anamnestic antibodies suggesting that the patient had gone through a clinically inapparent COVID-19 infection, which we conclude most likely contributed to his hypercoagulable state and led to the formation of significant thrombi impairing the patient's haemodynamics. The patient underwent a surgical thrombectomy; there were no post-operative thrombotic complications.Whole-genome sequencing (WGS) has shown tremendous potential in rapid diagnosis of drug-resistant tuberculosis (TB). In the current study, we performed WGS on drug-resistant Mycobacterium tuberculosis isolates obtained from Shanghai (n = 137) and Russia (n = 78). We aimed to characterise the underlying and high-frequency novel drug-resistance-conferring mutations, and also create valuable combinations of resistance mutations with high predictive sensitivity to predict multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB) phenotype using a bootstrap method. Most strains belonged to L2.2, L4.2, L4.4, L4.5 and L4.8 lineages. We found that WGS could predict 82.07% of phenotypically drug-resistant domestic strains. The prediction sensitivity for rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), ofloxacin (OFL), amikacin (AMK) and capreomycin (CAP) was 79.71%, 86.30%, 76.47%, 88.37%, 83.33%, 70.00% and 70.00%, respectively. The mutation combination with the highest sensitivity for MDR prediction was rpoB S450L + rpoB H445A/P + katG S315T + inhA I21T + inhA S94A, with a sensitivity of 92.17% (0.8615, 0.9646), and the mutation combination with highest sensitivity for XDR prediction was rpoB S450L + katG S315T + gyrA D94G + rrs A1401G, with a sensitivity of 92.86% (0.8158, 0.9796). The molecular information presented here will be of particular value for the rapid clinical detection of MDR- and XDR-TB isolates through laboratory diagnosis.

Stigma related to mental disorders is a barrier to quality mental healthcare. This scoping review aimed to synthesise literature on stigma related to mental disorders in Nepal to understand stigma processes. The anthropological concept of 'what matters most' to understand culture and stigma was used to frame the literature on explanatory models, manifestations, consequences, structural facilitators and mitigators, and interventions.

We conducted a scoping review with screening guided by the Preferred Reporting Items for Systematic Review and Meta-analysis Extension for Scoping Reviews (PRISMA-ScR). A structured search was done using three international databases (PsycINFO, Medline and Web of Science), one Nepali database (NepJol) and cross-referencing for publications from 1 January 2000 through 24 June 2020. The search was repeated to include structural stigma-related terms. Quality of quantitative studies was assessed using the Systematic Assessment of Quality in Observational Research (SAQOR) tool. Mycro 3 Thens targeting multiple domains. We suggest that stigma researchers should clarify conceptual models to inform study design and interpretations. There is a need to develop procedures for the systematic cultural adaptation of stigma assessment tools. Research should be conducted to understand the forms and drivers of structural stigma and to expand intervention research to evaluate strategies for stigma reduction.

To assess preventability of hospital-onset bacteremia and fungemia (HOB), we developed and evaluated a structured rating guide accounting for intrinsic patient and extrinsic healthcare-related risks.

HOB preventability rating guide was compared against a reference standard expert panel.

A 10-member panel of clinical experts was assembled as the standard of preventability assessment, and 2 physician reviewers applied the rating guide for comparison.

The expert panel independently rated 82 hypothetical HOB scenarios using a 6-point Likert scale collapsed into 3 categories preventable, uncertain, or not preventable. Consensus was defined as concurrence on the same category among ≥70% experts. Scenarios without consensus were deliberated and followed by a second round of rating.Two reviewers independently applied the rating guide to adjudicate the same 82 scenarios in 2 rounds, with interim revisions. Interrater reliability was evaluated using the κ (kappa) statistic.

Expert panel consensus criteria werHOB preventability.

Grief research in family carers of people with dementia has increased. We aimed to report the prevalence of pre-death and post-death grief and to synthesize associated factors and the relationship between pre-death factors and post-death grief and services used to manage grief.

(Prospero protocol CRD42020165071) We systematically reviewed literature from PsycINFO, MEDLINE, CINAHL, and ASSIA until April 2020. Effectiveness of intervention data and studies not written in English were excluded; qualitative studies were additionally excluded during study selection. Study quality was assessed using the Mixed Methods Appraisal Tool. Evidence was narratively summarized.

Family non-paid carers of somebody with any dementia type.

Validated measures of pre-death and/or post-death grief.

We included quantitative data from 55 studies (44 rated as high quality). Most included solely spouse or adult child carers. Forty-one studies reported pre-death grief, 12 post-death grief, and 6 service use; eight were longitudinal. 17% met the Prolonged Grief Disorder criteria pre-death (n = 1) and 6-26% (n = 4) of participants met the Complicated Grief criteria post-death. Being a spouse, less educated, caring for somebody with advanced dementia, and greater burden and depression were associated with higher pre-death grief. Lower education level and depression were predictive of higher post-death grief. Pre-death factors found to influence post-death grief were grief and depression. Limited service use evidence was reported.

Awareness of characteristics which increase the likelihood of higher grief can help identify those in need of support. Future research should focus on what supports or services are beneficial to grief experiences.

Awareness of characteristics which increase the likelihood of higher grief can help identify those in need of support. Future research should focus on what supports or services are beneficial to grief experiences.

The European Network for Health Technology Assessment (EUnetHTA) was established in 2006. During its final project phase (joint action 3 [JA3]), it undertook an activity to define the scientific and technical principles of a model of health technology assessment (HTA) cooperation in Europe. This policy article presents the key learnings from JA3 partners about developing a model of HTA cooperation.

There were two phases to the activity (i) A descriptive phase to describe the elements of HTA cooperation that were already in place in EUnetHTA JA3 and to identify which elements could be improved or were missing. (ii) An analytic phase synthesizing the data collected to identify learnings from the JA3 and to define the scientific and technical principles for a future model of HTA cooperation.

Learnings for developing HTA cooperation were identified in regard to the framework used to support the cooperation, the HTA activities undertaken, the involvement of internal and external actors, managing decision making and the required human resources and support services needed to undertake HTA activities and to coordinate collaboration.

These learnings coming from the experiences of the EUnetHTA JA3 are useful to inform discussions on a European Union regulation for HTA cooperation as well as subsequent work to set up the structures that will be defined in the regulation. The findings also have broader applicability and are relevant to individuals, groups, and organizations setting up HTA programs or establishing their own international collaborations.

These learnings coming from the experiences of the EUnetHTA JA3 are useful to inform discussions on a European Union regulation for HTA cooperation as well as subsequent work to set up the structures that will be defined in the regulation. The findings also have broader applicability and are relevant to individuals, groups, and organizations setting up HTA programs or establishing their own international collaborations.Didelphis albiventris is the opossum with the largest geographic distribution in Brazil and has a wide spectrum of helminth parasites. This study aimed to describe the species composition and analyse the structure of helminth communities of D. albiventris in two extremes of the Atlantic Forest in Brazil. The influence of host sex, body mass, age, helminth species richness and locality on the abundance and prevalence of the most prevalent helminth species was investigated. Ninety-five per cent of the animals were infected with at least one species. Nine helminth species were found the nematodes Aspidodera raillieti, Cruzia tentaculata, Trichuris didelphis and Trichuris minuta in the large intestine; Turgida turgida in the stomach; Travassostrongylus orloffi and Viannaia hamata; and the trematodes Brachylaima advena and Rhopalias coronatus in the small intestine. Three helminth morphospecies were also recovered the nematodes Hoineffia sp. and Viannaia sp. and a cestode in the small intestine. Cruzia tentaculata and V.