MIRO2 promotes cancer invasion and metastasis via MYO9B suppression of RhoA activity.

Metastasis to vital organs remains the leading cause of cancer-related deaths, emphasizing an urgent need for actionable targets in advanced-stage cancer. The role of mitochondrial Rho GTPase 2 (MIRO2) in prostate cancer growth was recently reported; however, whether MIRO2 is important for additional steps in the metastatic cascade is unknown. Here, we show that knockdown of MIRO2 ubiquitously reduces tumor cell invasion in vitro and suppresses metastatic burden in prostate and breast cancer mouse models.

An alternate synthetic pathway to nanoscopic LiFeS for energy storage.

Lithium-rich iron sulphide, LiFeS, exhibits reversible charge-storage both cationic and anionic sites, storing nearly 400 mA h g, but its synthesis is limited to solid-state methods that result in large primary particles. We describe an alternate solution-based, redox-mediated method to lithiate pyrite FeS, ultimately forming nanoscale LiFeS.

Assessing the landscape and charting paths: UK neurology trainees' opinions on neuroinflammation subspecialty.

Therapeutics of neuroinflammatory disorders including multiple sclerosis is one of the fastest growing areas in neurology. However, pressures on higher specialty training in neurology together with an expanding curriculum have led to challenges in adequately preparing trainees for a subspecialist career. In this study we set out to understand current perceptions and barriers to training in neuroinflammatory disorders among neurology trainees in the UK.

Humanizing cancer: The role of anthropomorphism and perceived efficacy in melanoma prevention.

This study investigates how melanoma anthropomorphism (i.e., the attribution of humanlike qualities to melanoma) interacts with individual differences in perceived efficacy to influence attitudes and intentions to perform preventive health behaviors.

Using disease-modifying treatments in multiple sclerosis: Association of British Neurologists (ABN) 2024 guidance.

The Association of British Neurologists last published guidelines on disease-modifying treatment (DMT) in multiple sclerosis (MS) in 2015. Since then, additional DMTs have been licensed and approved for prescribing within the National Health Service for relapsing-remitting MS, early primary progressive MS and active secondary progressive MS. This updated guidance provides a consensus-based approach to using DMTs.

Dependence of PAX3-FOXO1 chromatin occupancy on ETS1 at important disease-promoting genes exposes new targetable vulnerability in Fusion-Positive Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS), a malignancy of impaired myogenic differentiation, is the most common soft tissue pediatric cancer. PAX3-FOXO1 oncofusions drive the majority of the clinically more aggressive fusion-positive rhabdomyosarcoma (FP-RMS). Recent studies have established an epigenetic basis for PAX3-FOXO1-driven oncogenic processes.

Implementing vocational rehabilitation for people with multiple sclerosis in the UK National Health Service: a mixed-methods feasibility study.

Purpose: To implement a job retention vocational rehabilitation (VR) intervention (MSVR) for people with multiple sclerosis (MS) and their employers in the UK National Health Service (NHS).

Methods: Multicentre, single-arm feasibility study with post-intervention interviews. MSVR was delivered by an occupational therapist (OT).

Decarboxylative Cross-Coupling Enabled by Fe and Ni Metallaphotoredox Catalysis.

Decarboxylative cross-coupling of carboxylic acids and aryl halides has become a key transformation in organic synthesis to form C(sp)-C(sp) bonds. In this report, a base metal pairing between Fe and Ni has been developed with complementary reactivity to the well-established Ir and Ni metallaphotoredox reactions. Utilizing an inexpensive FeCl cocatalyst along with a pyridine carboxamidine Ni catalyst, a range of aryl iodides can be preferentially coupled to carboxylic acids over boronic acid esters, triflates, chlorides, and even bromides in high yields.

Polymer nanodiscs support the functional extraction of an artificial transmembrane cytochrome.

Polymer nanodiscs are an attractive alternative to surfactants for studying integral membrane proteins within their native lipid environment. Here, we investigate the use of such polymers to isolate a computationally-designed de novo membrane cytochrome named CytbX. We show that the block copolymers known as CyclAPols can efficiently extract CytbX directly from biomembranes and are compatible with the downstream purification and biophysical characterisation of this artificial protein.

Remembering Hypoxia: Uncovering the Long-Term Effects of Transient Oxygen Deprivation on IFN Signaling and Progression of Breast Cancer.

Hypoxia occurs in 90% of solid tumors and is strongly associated with an increased propensity for metastasis. Hypoxia induces tumor progression largely through inducing HIF-mediated transcription, resulting in alterations to tumor cell metabolism, as well as increases in migration and invasion. Hypoxia also results in a myriad of changes to the tumor microenvironment (TME).

Adipose tissue oxylipin profile changes with subclinical ketosis and depot in postpartum dairy cows.

Lipolysis of adipose tissue is a natural occurrence during the periparturient period in dairy cows. However, when lipolysis rates exceed the capacity of other tissues to used nonesterified fatty acids, it may lead to the development of ketosis and other diseases. Additionally, PUFA can become oxidized into oxylipins, which modulate inflammation and metabolism.

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.

Methods And Analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.

Brain reserve and physical disability in secondary progressive multiple sclerosis.

Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS.

The Story of Dr. Asa G. Yancey and Surgical Innovation in the Face of Discrimination.

Introduction: Dr. Asa G. Yancey published a surgical technique describing a pull - through of normal colon through a cuff of aganglionic colon to treat Hirschsprung disease in 1952, 12 y before Dr.

An EYA3/NF-κB/CCL2 signaling axis suppresses cytotoxic NK cells in the pre-metastatic niche to promote triple negative breast cancer metastasis.

Unlabelled: Patients with Triple Negative Breast Cancer (TNBC) exhibit high rates of metastases and poor prognoses. The Eyes absent (EYA) family of proteins are developmental transcriptional cofactors/phosphatases that are re-expressed and/or upregulated in numerous cancers. Herein, we demonstrate that EYA3 correlates with decreased survival in breast cancer, and that it strongly, and specifically, regulates metastasis via a novel mechanism that involves NF-kB signaling and an altered innate immune profile at the pre-metastatic niche (PMN).

Exploring the patient perspective in pulmonary hypertension.

The global impacts of pulmonary hypertension (PH) were formally recognised in 1973 at the 1st World Health Organization meeting dedicated to primary pulmonary hypertension, held in Geneva. Investigations into disease pathogenesis and classification led to the development of numerous therapies over the ensuing decades. While the impacts of the disease have been lessened due to treatments, the symptoms and adverse effects of PH and its therapies on patients' wellbeing and mental health remain significant.

A qualitative study exploring how vocational rehabilitation for people with multiple sclerosis can be integrated within existing healthcare services in the United Kingdom.

Background: To explore how a vocational rehabilitation (VR) intervention can be integrated within existing healthcare services for people with multiple sclerosis (MS) in the United Kingdom (UK) National Health Service (NHS).

Methods: Data from 37 semi-structured interviews with 22 people with MS, eight employers, and seven healthcare professionals were analysed using a framework method informed by the Consolidated Framework for Implementation Research and an intervention logic model.

Results: Four themes were identified relating to the structure of current NHS services, how to improve access to and awareness of VR services, the collaboration between internal and external networks, and the benefits of integrating VR within the NHS services.

Role of land-ocean interactions in stepwise Northern Hemisphere Glaciation.

The investigation of triggers causing the onset and intensification of Northern Hemisphere Glaciation (NHG) during the late Pliocene is essential for understanding the global climate system, with important implications for projecting future climate changes. Despite their critical roles in the global climate system, influences of land-ocean interactions on high-latitude ice sheets remain largely unexplored. Here, we present a high-resolution Asian dust record from Ocean Drilling Program Site 1208 in the North Pacific, which lies along the main route of the westerlies.

PhIGFBP-1 to predict preterm birth in asymptomatic women: A systematic review and meta-analysis.

Objective: To assess the prognostic value of cervicovaginal phosphorylated insulin-like growth factor-binding protein 1 (phIGFBP-1) to predict preterm birth in asymptomatic women during the second trimester of pregnancy.

Study Design: This is a systematic review and meta-analysis of prognostic factor studies. We searched MEDLINE and Embase to identify cohort studies on the prognostic value of mid-trimester phIGFBP-1 on preterm birth in asymptomatic women.

Surgery and Surgical Training Before Graduate Medical Education: A Blue Ribbon Committee II, Medical Student Education Subcommittee Report.

Objective: To update and add to the first report commissioned by the Blue Ribbon Committee (BRC) about 20 years prior.

Background: Following a summit in late 2022 commissioned by the American Board of Surgery regarding competency-based reforms in surgical education and through a partnership with the American College of Surgeons and other stakeholders, a BRC-II on surgical education was formed. The BRC-II would have 7 subcommittees.

The Effect of Subclinical Ketosis on the Peripheral Blood Mononuclear Cell Inflammatory Response and Its Crosstalk with Depot-Specific Preadipocyte Function in Dairy Cows.

During the periparturient period, cows undergo heightened energy demands at lactation onset, paired with reduced dry matter intake, leading to negative energy balance (NEB). Excessive lipolysis-driven adipose tissue remodeling, triggered by NEB, significantly contributes to ketosis in periparturient dairy cows. However, the role of peripheral blood mononuclear cells (PBMCs) in the pathogenesis of ketosis and in modulating adipose tissue function remains poorly understood.

The Impact of COVID-19 on the Employment of People With Multiple Sclerosis: A Multiple Methods Study.

Background: The COVID-19 pandemic led to approximately half of the working population in the United Kingdom being unable to work temporarily. This study aims to understand the employment needs and experiences of people with multiple sclerosis (MS) in the UK during this period.

Methods: Multiple methods were used, including an online survey and follow-up interviews with people with MS who were employed prior to the start of the pandemic restrictions in March 2020.

Extracellular matrix modulates depot-specific adipogenic capacity in adipose tissue of dairy cattle.

Adipose tissue (AT) expands through both hyperplasia and hypertrophy. During adipogenesis, adipose stromal and progenitor cells (ASPC) proliferate and then accumulate lipids, influenced by the local AT microenvironment. Increased adipogenic capacity is desirable as it relates to metabolic health, especially in transition dairy cows where excess free fatty acids in circulation can compromise metabolic and immune health.