Developing a digital phenotype to subdivide adult immunosuppressed COVID-19 outcomes within the English Primary Care Sentinel Network.

Background: Adults classified as immunosuppressed have been disproportionately affected by the COVID-19 pandemic. Compared to the immunocompetent, certain patients are at increased risk of suboptimal vaccine response and adverse health outcomes if infected. However, there has been insufficient work to pinpoint where these risks concentrate within the immunosuppressed spectrum; surveillance efforts typically treat the immunosuppressed as a single entity, leading to wide confidence intervals.

Prognostic and therapeutic implications of tumor-restrictive type III collagen in the breast cancer microenvironment.

Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and bioinformatic experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer.

Sonic Hedgehog activates prostaglandin signaling to stabilize primary cilium length.

Sonic Hedgehog (SHH) is a driver of embryonic patterning that, when corrupted, triggers developmental disorders and cancers. SHH effector responses are organized through primary cilia (PC) that grow and retract with the cell cycle and in response to extracellular cues. Disruption of PC homeostasis corrupts SHH regulation, placing significant pressure on the pathway to maintain ciliary fitness.

Cytoneme signaling provides essential contributions to mammalian tissue patterning.

During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes.

National public health response to an outbreak of toxigenic Corynebacterium diphtheriae among asylum seekers in England, 2022: a descriptive epidemiological study.

Background: In July, 2022, an increase in diphtheria cases caused by toxigenic Corynebacterium diphtheriae (C diphtheriae) was reported among asylum seekers arriving by small boats to England. Rising case numbers presented challenges for case and contact management in initial reception centres, prompting changes to national guidance and implementation of population-based control measures. This study aimed to describe the outbreak of toxigenic C diphtheriae among asylum seekers arriving by small boats to England during 2022 by use of national surveillance data.

Working alongside next of kin to enhance discharge: A quality improvement collaboration to co-design discharge for mental health patients.

Objectives: Mental health (MH) patients seen in the emergency department (ED) setting are often viewed in isolation, outside of the context of their loved ones, the next of kin (NOK). This is especially problematic when a patient is detained under the mental health act. This project aimed to improve this engagement.

A systematic review of the burden of, access to services for and perceptions of patients with overweight and obesity, in humanitarian crisis settings.

Introduction: Excess body weight causes 4 million deaths annually across the world. The number of people affected by humanitarian crises stands at a record high level with 1 in 95 people being forcibly displaced. These epidemics overlap.

Tumor-restrictive type III collagen in the breast cancer microenvironment: prognostic and therapeutic implications.

Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer.

Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis.

Background: Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender.

Methods: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions.

Analysis of the UK Government's 10-Year Drugs Strategy-a resource for practitioners and policymakers.

In 2021, during a drug-related death crisis in the UK, the Government published its ten-year drugs strategy. This article, written in collaboration with the Faculty of Public Health and the Association of Directors of Public Health, assesses whether this Strategy is evidence-based and consistent with international calls to promote public health approaches to drugs, which put 'people, health and human rights at the centre'. Elements of the Strategy are welcome, including the promise of significant funding for drug treatment services, the effects of which will depend on how it is utilized by services and local commissioners and whether it is sustained.

Sleep and sexual satisfaction in couples with matched and mismatched chronotypes: A dyadic cross-sectional study.

Chronotype can be defined as an overt expression of circadian rhythmicity in an individual that dictates tendencies towards being a morning or evening person - also referred to as 'morningness' or 'eveningness.' Chronotypes generally impact preferred bed and wake times, in addition to a range of personal and social factors. This study examined how matching/mismatching chronotypes within relationships impact sexual satisfaction and sleep quality.

Cysteine-rich domain of type III collagen N-propeptide inhibits fibroblast activation by attenuating TGFβ signaling.

TGFβ is a key regulator of the dynamic reciprocity between cells and the extracellular matrix that drives physiologic and pathologic responses in both tissue repair and tumor microenvironments. Our studies define type III Collagen (Col3) as a suppressor of scar formation and desmoplasia through its effects, in part, on myofibroblasts. TGFβ stimulates activation of myofibroblasts, and here, we demonstrate that cultured Col3-deficient fibroblasts have increased TGFβ signaling compared to wild-type fibroblasts.

Facemasks and ferrous metallurgy: improving gasification reactivity of low-volatile coals using waste COVID-19 facemasks for ironmaking application.

The global pandemic response to COVID-19 has led to the generation of huge volumes of unrecyclable plastic waste from single use disposable face coverings. Rotary hearth furnaces can be used to recover Zn and Fe from non-recyclable steelmaking by-product dusts, and waste plastic material such as facemasks could be utilized as a supplementary reductant for the rotary hearth furnace (RHF), but their fibrous form makes milling and processing to appropriate sizing for RHF application extremely challenging. A scalable method of grinding facemasks to powder by melting and mixing with Welsh coal dust reported herein provides a solution to both environmental challenges.

The utility of scribes in the academic dermatology clinic: An opportunity for mutual benefit to patients, trainees, and shareholders.

Electronic medical records have made great advances in the provision of quality health care but have increased physician workload and often limit face-to-face time with patients. These effects are particularly felt in the academic dermatology clinic, a critical time of practice development. Time constraints from implementation of electronic medical records have resulted in low patient volume and reduced educational opportunities.

Setipiprant for Androgenetic Alopecia in Males: Results from a Randomized, Double-Blind, Placebo-Controlled Phase 2a Trial.

Purpose: To evaluate oral setipiprant versus placebo for scalp hair growth in men with androgenetic alopecia (AGA).

Patients And Methods: Males aged 18 to 49 years with AGA were enrolled in a double-blind, multicenter, 32-week, phase 2a trial; randomized to twice-daily (BID) 1000-mg (2×500 mg for a total daily dose of 2000 mg) setipiprant tablets or placebo for 24 weeks; and assessed at weeks 4, 8, 16, and 24, with a week 32 follow-up. The study initially included a finasteride 1-mg once-daily group, removed by protocol amendment.

Analysis of Dispatched Protein Processing and Sonic Hedgehog Ligand Release.

The 12-pass transmembrane protein Dispatched (DISP) is essential for Sonic Hedgehog (SHH) release from ligand-producing cells and is indispensable for establishment of the SHH morphogen gradient during tissue patterning. Regulatory events controlling DISP release of SHH are not yet fully characterized. We recently demonstrated that DISP is cleaved by FURIN proprotein convertase at a conserved site in its first extracellular loop.

Cytoneme delivery of Sonic Hedgehog from ligand-producing cells requires Myosin 10 and a Dispatched-BOC/CDON co-receptor complex.

Morphogens function in concentration-dependent manners to instruct cell fate during tissue patterning. The cytoneme morphogen transport model posits that specialized filopodia extend between morphogen-sending and responding cells to ensure that appropriate signaling thresholds are achieved. How morphogens are transported along and deployed from cytonemes, how quickly a cytoneme-delivered, receptor-dependent signal is initiated, and whether these processes are conserved across phyla are not known.

Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs: a systematic review and meta-analysis.

Background And Aim: Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID.

The Significance of Metal Coordination in Imidazole-Functionalized Metal-Organic Frameworks for Carbon Dioxide Utilization.

The grafting of imidazole species onto coordinatively unsaturated sites within metal-organic framework MIL-101(Cr) enables enhanced CO capture in close proximity to catalytic sites. The subsequent combination of CO and epoxide binding sites, as shown through theoretical findings, significantly improves the rate of cyclic carbonate formation, producing a highly active CO utilization catalyst. An array of spectroscopic investigations, in combination with theoretical calculations reveal the nature of the active sites and associated catalytic mechanism which validates the careful design of the hybrid MIL-101(Cr).

Unique behavior of dermal cells from regenerative mammal, the African Spiny Mouse, in response to substrate stiffness.

The African Spiny Mouse (Acomys spp.) is a unique outbred mammal capable of full, scar-free skin regeneration. In vivo, we have observed rapid reepithelialization and deposition of normal dermis in Acomys after wounding.