Integration of Through-Sapphire Substrate Machining with Superconducting Quantum Processors.

A sapphire machining process integrated with intermediate-scale quantum processors is demonstrated. The process allows through-substrate electrical connections, necessary for low-frequency mode-mitigation, as well as signal-routing, which are vital as quantum computers scale in qubit number, and thus dimension. High-coherence qubits are required to build fault-tolerant quantum computers and so material choices are an important consideration when developing a qubit technology platform.

A novel workflow for multi-modal imaging of musculoskeletal tissues.

According to the World Health Organization (WHO) musculoskeletal conditions are a leading contributor to disability worldwide. This fact is often somewhat overlooked, since musculoskeletal conditions are less likely to be associated with mortality. Nonetheless, treatments, therapies and management of these conditions are extremely costly to national healthcare systems.

Time-of-day control of mitochondria regulates NLRP3 inflammasome activation in macrophages.

Macrophages are innate immune cells that orchestrate the process of inflammation, which varies across time of day. This ensures appropriate biological timing of the immune response with the external environment. The NLRP3 inflammasome mediates IL-1-family cytokine release via pyroptosis.

Botulinum Toxin for the Treatment of Raynaud's Conditions of the Hand: Clinical Practice Updates and Future Directions.

Raynaud's conditions of the hand, referred to commonly as Raynaud's phenomenon, both primary and secondary, represents a spectrum of disorders affecting the digits, characterised by recurrent episodes of vasospasm that result in a triad of symptoms: pain, pallor, and cyanosis. Various therapies, ranging from conservative hand therapy techniques to surgical sympathectomy, have been explored with inconsistent results. Recently, the local administration of botulinum toxin type-A (BTX-A) has re-emerged as a treatment option for this condition.

A Risk Prediction Model to Identify People Living with HIV Who are High-risk for Disengagement from Care after HIV Diagnosis in South Africa.

The provision of ART in South Africa has transformed the HIV epidemic, resulting in an increase in life expectancy by over 10 years. Despite this, nearly 2 million people living with HIV are not on treatment. The objective of this study was to develop and externally validate a practical risk assessment tool to identify people with HIV (PWH) at highest risk for attrition from care after testing.

Tissue engineering approaches for dental pulp regeneration: The development of novel bioactive materials using pharmacological epigenetic inhibitors.

The drive for minimally invasive endodontic treatment strategies has shifted focus from technically complex and destructive root canal treatments towards more conservative vital pulp treatment. However, novel approaches to maintaining dental pulp vitality after disease or trauma will require the development of innovative, biologically-driven regenerative medicine strategies. For example, cell-homing and cell-based therapies have recently been developed and trialled in preclinical models to study dental pulp regeneration.

Toxin for Treating Raynaud Conditions in Hands (The TORCH Study): A Systematic Review and Meta-analysis.

Background: Raynaud disease of the hands is a complex disorder resulting in inappropriate constriction and/or insufficient dilation in microcirculation. There is an emerging role for botulinum toxin type A (BTX-A) in the treatment armamentarium for refractory Raynaud disease. The aim of this systematic review was to critically evaluate the management of primary and secondary Raynaud disease treated with BTX-A intervention.

Liver Fibrosis Assessed Via Noninvasive Tests Is Associated With Incident Heart Failure in a General Population Cohort.

Background & Aims: The aim of this study was to determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association.

Methods: Using UK Biobank data, we prospectively examined the relationship between noninvasive fibrosis markers (nonalcoholic fatty liver disease [NAFLD] fibrosis score [NFS], Fibrosis-4 [FIB-4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n = 413,860). Cox-regression estimated hazard ratios (HRs) for incident heart failure.

Reproducible Synthesis of Biocompatible Albumin Nanoparticles Designed for Intra-articular Administration of Celecoxib to Treat Osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis, with intra-articular (IA) delivery of therapeutics being the current best option to treat pain and inflammation. However, IA delivery is challenging due to the rapid clearance of therapeutics from the joint and the need for repeated injections. Thus, there is a need for long-acting delivery systems that increase the drug retention time in joints with the capacity to penetrate OA cartilage.

Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: A retrospective study.

Purpose: This study investigated thyroid dysfunction with immune checkpoint inhibitors (ICIs) in terms of proportions affected, risk factors, thyroid sequelae, and overall survival (OS).

Methods: Among patients with normal baseline free T4 (fT4) and thyroid stimulating hormone (TSH) receiving ICIs at a large cancer centre, proportions of hyperthyroidism/hypothyroidism were determined (any, subclinical [normal fT4, abnormal TSH], overt [abnormal fT4, abnormal TSH], isolated hyperthyroxinaemia/hypothyroxinaemia and secondary) with onset times and subsequent thyroid statuses. Associations of overt dysfunction with OS were estimated using Cox regression and methods robust to immortal time bias (time-dependent Cox regression and 3- and 6-month landmark analyses).

Prognostic and predictive value of non-steroidal anti-inflammatory drugs in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

Background: Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial.

Immunomodulatory Strategies for Cartilage Regeneration in Osteoarthritis.

Osteoarthritis (OA) is the most prevalent musculoskeletal disorder and a leading cause of disability globally. Although many efforts have been made to treat this condition, current tissue engineering (TE) and regenerative medicine strategies fail to address the inflammatory tissue environment that leads to the rapid progression of the disease and prevents cartilage tissue formation. First, this review addresses in detail the current anti-inflammatory therapies for OA with a special emphasis on pharmacological approaches, gene therapy, and mesenchymal stromal cell (MSC) intra-articular administration, and discusses the reasons behind the limited clinical success of these approaches at enabling cartilage regeneration.

A single-site retrospective review of in-hospital stroke.

Background: In-hospital stroke refers to a stroke arising in a patient during hospital admission for another condition. Between 2 and 17% of all inpatient strokes are in-hospital strokes.

Aim: To compare the outcomes and performance on quality-of-care stroke measures of in-hospital stroke cases with community-onset strokes.

Gene of the month: cancer testis antigen gene 1b (NY-ESO-1).

Cancer testis antigen gene 1B (CTAG1B) and its associated gene product; New York oesophageal squamous carcinoma 1 (NY-ESO-1), represent a unique and promising target for cancer immunotherapy. As a member of the cancer testis antigen family (CTA), the protein's restricted expression pattern and ability to elicit spontaneous humoural and cellular immune responses has resulted in a plethora of novel modalities and approaches attempting to harness its immunotherapeutic anti-cancer potential. Here, we discuss the structure and function of CTAG1B/NY-ESO-1 in both health and disease, immunohistochemical detection, as well as the most promising advances in the development of associated anti-cancer therapies.

Chemsex and Harm Reduction Practices Among Men Who Have Sex with Men in Malaysia: Findings from a Qualitative Study.

Chemsex is a form of sexualized drug use commonly practiced among MSM with psychoactive substances, such as methamphetamine. While this phenomenon has gained global attention in the past two decades, there is a dearth of empirical data to inform culturally competent interventions. The current work investigates the socio-contextual factors related to chemsex and harm reduction practices among Malaysian MSM.

Clinical validation of in-hospital stroke diagnosis.

Objective: In-hospital stroke cases occur during hospitalization for another diagnosis and reflect a clinically distinct cohort from community-onset stroke. The objective was to validate the diagnostic accuracy of in-hospital stroke identification in stroke audit data at a large teaching hospital.

Methods: A retrospective clinical validation of in-hospital stroke diagnoses from two linked data sources was completed for a 2-year period from January 1 2020 to December 31 2021.

Prognostic and predictive value of metformin in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma.

Background: Metformin is a commonly prescribed and well-tolerated medication. In laboratory studies, metformin suppresses BRAF wild-type melanoma cells but accelerates the growth of BRAF-mutated cells. This study investigated the prognostic and predictive value of metformin, including with respect to BRAF mutation status, in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 randomised controlled trial.

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.

Background: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD.

Methods: A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.

Probing spin dynamics of ultra-thin van der Waals magnets via photon-magnon coupling.

Layered van der Waals (vdW) magnets can maintain a magnetic order even down to the single-layer regime and hold promise for integrated spintronic devices. While the magnetic ground state of vdW magnets was extensively studied, key parameters of spin dynamics, like the Gilbert damping, crucial for designing ultra-fast spintronic devices, remains largely unexplored. Despite recent studies by optical excitation and detection, achieving spin wave control with microwaves is highly desirable, as modern integrated information technologies predominantly are operated with these.

Chronic consumption of a blend of inulin and arabinoxylan reduces energy intake in an ad libitum meal but does not influence perceptions of appetite and satiety: a randomised control-controlled crossover trial.

Purpose: Prebiotic foods can be used to increase production of short-chain fatty acids (SCFA) in the gut. Of the SCFA, propionate is credited with the strongest anorectic activity. In previous work, a 50/50 blend of inulin and arabinoxylan was produced (I + AX) that significantly increased propionate production in an in vitro gut model.

Social determinants of health derived from people with opioid use disorder: Improving data collection, integration and use with cross-domain collaboration and reproducible, data-centric, notebook-style workflows.

Deriving social determinants of health from underserved populations is an important step in the process of improving the well-being of these populations and in driving policy improvements to facilitate positive change in health outcomes. Collection, integration, and effective use of clinical data for this purpose presents a variety of specific challenges. We assert that combining expertise from three distinct domains, specifically, medical, statistical, and computer and data science can be applied along with provenance-aware, self-documenting workflow tools.

Engagement in Chemsex among Men Who Have Sex with Men (MSM) in Malaysia: Prevalence and Associated Factors from an Online National Survey.

Background: Chemsex is the use of illicit drugs—particularly methamphetamine, gamma hydroxybutyrate (GHB), and gamma-butyrolactone (GBL)—to enhance sexual activity. Chemsex, which occurs primarily among communities of men who have sex with men (MSM), is associated with greater HIV risk behaviors, including multiple sex partners, group sex, condomless sex, and injection drug use. Despite evidence showing chemsex engagement among Malaysian MSM, there is a paucity of research on chemsex among MSM in Malaysia.

Greater muscle volume and muscle fat infiltrate in the deep cervical spine extensor muscles (multifidus with semispinalis cervicis) in individuals with chronic idiopathic neck pain compared to age and sex-matched asymptomatic controls: a cross-sectional study.

Muscle size and composition (muscle volume and muscle fat infiltrate [MFI]) may provide insight into possible mechanisms underpinning chronic idiopathic neck pain, a common condition with no definitive underlying pathology. In individuals with chronic idiopathic neck pain > 3 months and age- and sex-matched asymptomatic controls, muscle volumes of levator scapulae, multifidus including semispinalis cervicis (MFSS), semispinalis capitis, splenius capitis including splenius cervicis (SCSC), sternocleidomastoid and longus colli from C3 through T1 were quantified from magnetic resonance imaging. Between-group differences were determined using linear mixed models, accounting for side (left or right), muscle, spinal level, sex, age, and body mass index (BMI).

Child and adult adiposity and subtype-specific endometrial cancer risk: a multivariable Mendelian randomisation study.

Increased adiposity is a known risk factor for endometrial cancer (EC). This study aimed to disentangle the separate causal roles of child and adult adiposity on EC risk in adults, including endometrioid and non-endometrioid histological subtypes using multivariable Mendelian randomisation. These analyses employed genetic associations derived from UK Biobank as proxies for child and adult body size in 12,906 cases and 108,979 controls that participated in the Endometrial Cancer Association Consortium.

Near-Surface ^{125}Te^{+} Spins with Millisecond Coherence Lifetime.

Impurity spins in crystal matrices are promising components in quantum technologies, particularly if they can maintain their spin properties when close to surfaces and material interfaces. Here, we investigate an attractive candidate for microwave-domain applications, the spins of group-VI ^{125}Te^{+} donors implanted into natural Si at depths as shallow as 20 nm. We show that surface band bending can be used to ionize such near-surface Te to spin-active Te^{+} state, and that optical illumination can be used further to control the Te donor charge state.