CARD14 signalosome formation is associated with its endosomal relocation and mTORC1-induced keratinocyte proliferation.

Rare mutations in CARD14 promote psoriasis by inducing CARD14-BCL10-MALT1 complexes that activate NF-κB and MAP kinases. Here, the downstream signalling mechanism of the highly penetrant CARD14E138A alteration is described. In addition to BCL10 and MALT1, CARD14E138A associated with several proteins important in innate immune signalling.

Fibroblast senescence-associated extracellular matrix promotes heterogeneous lung niche.

Senescent cell accumulation in the pulmonary niche is associated with heightened susceptibility to age-related disease, tissue alterations, and ultimately a decline in lung function. Our current knowledge of senescent cell-extracellular matrix (ECM) dynamics is limited, and our understanding of how senescent cells influence spatial ECM architecture changes over time is incomplete. Herein is the design of an model of senescence-associated extracellular matrix (SA-ECM) remodeling using a senescent lung fibroblast-derived matrix that captures the spatiotemporal dynamics of an evolving senescent ECM architecture.

The FAM13A Long Isoform Regulates Cilia Movement and Coordination in Airway Mucociliary Transport.

Single nucelotide polymorphisms (SNPs) at the locus are among the most commonly reported risk alleles associated with chronic obstructive pulmonary disease (COPD) and other respiratory diseases; however, the physiological role of FAM13A is unclear. In humans, two major protein isoforms are expressed at the locus: "long" and "short," but their functions remain unknown, partly because of a lack of isoform conservation in mice. We performed in-depth characterization of organotypic primary human airway epithelial cell subsets and show that multiciliated cells predominantly express the FAM13A long isoform containing a putative N-terminal Rho GTPase-activating protein (RhoGAP) domain.

Automated brightfield layerwise evaluation in three-dimensional micropatterning via two-photon polymerization.

Two-photon polymerization (TPP) is an advanced 3D fabrication technique capable of creating features with submicron precision. A primary challenge in TPP lies in the facile and accurate characterization of fabrication quality, particularly for structures possessing complex internal features. In this study, we introduce an automated brightfield layerwise evaluation technique that enables a simple-to-implement approach for in situ monitoring and quality assessment of TPP-fabricated structures.

Remote consultations in community mental health: A qualitative study of clinical teams.

Unlabelled: WHAT IS KNOWN ON THE SUBJECT?: Mental health care can be delivered remotely through video and telephone consultations. Remote consultations may be cheaper and more efficient than in person consultations.

What The Paper Adds To Existing Knowledge: Accessing community mental health care through remote consultations is perceived as not possible or beneficial for all service users.

Improved Indicators for Subnational Unmet Antiretroviral Therapy Need in the Health System: Updates to the Naomi Model in 2023.

Background: Quantifying subnational need for antiretroviral therapy (ART) for HIV is challenging because people living with HIV (PLHIV) access health facilities in areas that may differ from their residence. We defined and demonstrated new indicators for PLHIV treatment needed to guide health system target setting and resource allocation.

Setting: Botswana.

Multi-nodal basin drainage in lower limb melanoma.

Lymph node status is an important factor that influences outcomes in melanoma. Whilst certain anatomical areas have multiple-nodal basin drainage, limb melanomas are thought to have more predictable lymphatic drainage patterns, with lower limb melanomas reliably draining to the corresponding ipsilateral inguinal lymph node basin with occasional popliteal drainage. Here we share our unique experience of a patient with a lower limb melanoma demonstrating sentinel lymph nodes, and subsequent metastatic spread, in both the ipsilateral and contralateral inguinal lymph node basins, highlighting an important learning point with respect to our clinical examination of melanoma patients.

Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial.

Background: In the GLOW study, fixed-duration ibrutinib-venetoclax showed superior progression-free survival versus chlorambucil-obinutuzumab in patients with previously untreated chronic lymphocytic leukaemia who were older or had comorbidities, or both, at a median follow up of 27·7 months. In this Article, we report updated outcomes from GLOW after a 46-month median follow-up.

Methods: GLOW was a randomised, multicentre, phase 3 study done at 67 hospital centres across 14 countries.

Longitudinal Associations Between Autistic Traits, Self-compassion, Anxiety and Depression in Autistic and Non-autistic Adults Without Intellectual Disability.

Purpose: Previous cross-sectional research suggests self-compassion may mediate associations between autistic traits and mental health in autistic and non-autistic adults. However, no research to date has examined these relationships longitudinally. In this study, we used a cross-lagged panel analysis to examine correlations over time between autistic traits, self-compassion, and anxiety/depression.

Structural insights into the activation of ataxia-telangiectasia mutated by oxidative stress.

Ataxia-telangiectasia mutated (ATM) is a master kinase regulating DNA damage response that is activated by DNA double-strand breaks. However, ATM is also directly activated by reactive oxygen species, but how oxidative activation is achieved remains unknown. We determined the cryo-EM structure of an HO-activated ATM and showed that under oxidizing conditions, ATM formed an intramolecular disulfide bridge between two protomers that are rotated relative to each other when compared to the basal state.

Spatio-temporal estimates of HIV risk group proportions for adolescent girls and young women across 13 priority countries in sub-Saharan Africa.

The Global AIDS Strategy 2021-2026 identifies adolescent girls and young women (AGYW) as a priority population for HIV prevention, and recommends differentiating intervention portfolios geographically based on local HIV incidence and individual risk behaviours. We estimated prevalence of HIV risk behaviours and associated HIV incidence at health district level among AGYW living in 13 countries in sub-Saharan Africa. We analysed 46 geospatially-referenced national household surveys conducted between 1999-2018 across 13 high HIV burden countries in sub-Saharan Africa.

Changes in parental sleep from pregnancy to postpartum: A meta-analytic review of actigraphy studies.

Sleep changes in new parents are widely observed but there is no extant meta-analysis of changes to sleep parameters in this group. We completed a meta-analysis of changes in actigraphy-measured parent sleep between pregnancy and the end of the first year of a child's life. A search of six databases was completed.

Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial.

Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis <18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI.

Single-wavelength, single-shot pulse oximetry using an LED-generated vector beam.

Photoplethysmography (PPG) is an optical technique that monitors blood oxygen saturation levels, typically with the use of pulse oximeters. Conventional pulse oximetry estimates the ratio of light absorbed at two wavelengths. Attempts have been made to improve the precision of these measurements by using polarized light, with the tradeoff of requiring multiple sequential measurements.

Capturing the COVID-19 Crisis through Public Health and Social Measures Data Science.

In response to COVID-19, governments worldwide are implementing public health and social measures () that substantially impact many areas beyond public health. The new field of data science collects, structures, and disseminates data on ; here, we report the main achievements, challenges, and focus areas of this novel field of research.

PriorVAE: encoding spatial priors with variational autoencoders for small-area estimation.

Gaussian processes (GPs), implemented through multivariate Gaussian distributions for a finite collection of data, are the most popular approach in small-area spatial statistical modelling. In this context, they are used to encode correlation structures over space and can generalize well in interpolation tasks. Despite their flexibility, off-the-shelf GPs present serious computational challenges which limit their scalability and practical usefulness in applied settings.

Quantifying Cell-Derived Changes in Collagen Synthesis, Alignment, and Mechanics in a 3D Connective Tissue Model.

Dysregulation of extracellular matrix (ECM) synthesis, organization, and mechanics are hallmark features of diseases like fibrosis and cancer. However, most in vitro models fail to recapitulate the three-dimensional (3D) multi-scale hierarchical architecture of collagen-rich tissues and as a result, are unable to mirror native or disease phenotypes. Herein, using primary human fibroblasts seeded into custom fabricated 3D non-adhesive agarose molds, a novel strategy is proposed to direct the morphogenesis of engineered 3D ring-shaped tissue constructs with tensile and histological properties that recapitulate key features of fibrous connective tissue.

Risk scores for predicting HIV incidence among adult heterosexual populations in sub-Saharan Africa: a systematic review and meta-analysis.

Introduction: Several HIV risk scores have been developed to identify individuals for prioritized HIV prevention in sub-Saharan Africa. We systematically reviewed HIV risk scores to: (1) identify factors that consistently predicted incident HIV infection, (2) review inclusion of community-level HIV risk in predictive models and (3) examine predictive performance.

Methods: We searched nine databases from inception until 15 February 2021 for studies developing and/or validating HIV risk scores among the heterosexual adult population in sub-Saharan Africa.

Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England.

Background: Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.

Molecular mechanisms of APC/C release from spindle assembly checkpoint inhibition by APC/C SUMOylation.

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) is coordinated with the attachment of sister chromatids to the mitotic spindle. APC/C SUMOylation on APC4 ensures timely anaphase onset and chromosome segregation.

A Potent and Selective Kallikrein-5 Inhibitor Delivers High Pharmacological Activity in Skin from Patients with Netherton Syndrome.

Regulation of proteolytic activity in the skin plays a pivotal role in epidermal homeostasis. This is best exemplified in Netherton syndrome, a severe genetic skin condition caused by loss-of-function mutations in the gene serine protease inhibitor Kazal-type 5 encoding lympho-epithelial Kazal-type-related inhibitor, a serine protease inhibitor that regulates kallikrein (KLK)-related peptidase 5, 7, and 14 activities. KLK5 plays a central role in stratum corneum shedding and inflammatory cell signaling, activates KLK7 and KLK14, and is therefore an optimal therapeutic target.

Visualization of probiotics via epifluorescence microscopy and fluorescence in situ hybridization (FISH).

Aerobic plate counts, the standard for bacterial enumeration in the probiotic industry, can be biased towards fast-growing organisms that replicate on synthetic media and can significantly underestimate total bacterial abundance. Culture-independent approaches such as fluorescence in situ hybridization (FISH) hold promise as a means to rapidly and accurately enumerate bacteria in probiotic products. In addition, FISH has the potential to more accurately represent bacterial growth dynamics in the environment in which products are applied without imposing additional growth constraints that are required for enumeration via plate counts.

Self-compassion as a mediator of the association between autistic traits and depressive/anxious symptomatology.

In this study, we asked 164 undergraduate students to complete an online questionnaire. The questionnaire measured the students' levels of autistic traits, self-compassion, and experience of anxiety and depression. We were interested in knowing if self-compassion (defined as the extension of kindness to oneself when faced with challenges) had any influence on the relationship between autistic traits and experiences of anxiety and depression.