Resistance mechanisms to immune checkpoint inhibitors: updated insights.

The last decade has witnessed unprecedented succusses with the use of immune checkpoint inhibitors in treating cancer. Nevertheless, the proportion of patients who respond favorably to the treatment remained rather modest, partially due to treatment resistance. This has fueled a wave of research into potential mechanisms of resistance to immune checkpoint inhibitors which can be classified into primary resistance or acquired resistance after an initial response.

The variable relationship between the National Early Warning Score on admission to hospital, the primary discharge diagnosis, and in-hospital mortality.

Background: Patients with an elevated admission National Early Warning Score (NEWS) are more likely to die while in hospital. However, it is not known if this increased mortality risk is the same for all diagnoses. The aim of this study was to determine and compare the increased risk of in-hospital mortality associated with an elevated NEWS and different primary discharge diagnoses in unselected emergency admissions to a UK university teaching hospital.

Iron management and exercise training in individuals with chronic kidney disease: lived experiences.

Background: Non-anaemic iron deficiency is highly prevalent in people living with chronic kidney disease (CKD) but is underdiagnosed and undertreated, especially in earlier stages of CKD. A multicentre trial assessing the effect of intravenous iron supplementation in iron-deficiency but not anaemic people with CKD included a qualitative sub-study that aimed to explore the patient experience and psychosocial impact of living with CKD and iron deficiency, and the experience of the therapeutic intervention (intravenous iron and exercise).

Methods: Semi-structured interviews were conducted with 23 trial participants blinded to treatment.

Small molecules in idiopathic inflammatory myopathies: a systematic review and a multicenter case series about Janus kinase inhibitors and apremilast.

Objective: Idiopathic inflammatory myopathies (IIM) are rare autoimmune diseases that primarily affect striated muscles; skin, joints, and lungs may be involved with different degrees of severity. Traditional treatment relies on high-dose glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs.

Methods: A growing amount of evidence is demonstrating the potential role of novel treatments in the management of IIM.

Reflecting on the impact of the COVID pandemic on patient management and its subsequent influence on long-term outcomes: a case-control study in the field of esophago-gastric cancer.

Background: The delivery of cancer services changed significantly during the COVID-19 pandemic. This study aimed to describe changes in presentations, assess the change in recommendations by the MDT during the pandemic, and describe the subsequent long-term impact of these changes on survival rates in patients with EG cancer.

Methods: A retrospective cohort study was designed comparing three patient groups of those referred to EG MDT in the same 6-month period pre-pandemic (PP;2019) during the initial phase of the pandemic (P1;2020) and the year after the initial phase (P2;2021).

Effect of Fitness Level on Time Course of Recovery After Acute Strength and High-Intensity Interval Training.

Grammenou, M, Kendall, KL, Wilson, CJ, Porter, T, Laws, SM, and Haff, GG. Effect of fitness level on time course of recovery after acute strength and high-intensity interval training. J Strength Cond Res 38(12): 2055-2064, 2024-The aim was to investigate time course of recovery after acute bouts of strength (STR) and high-intensity interval training (HIIT).

Effect of Fitness Level on Time Course of Recovery After Acute Strength and High-Intensity Interval Training.

Grammenou, M, Kendall, KL, Wilson, CJ, Porter, T, Laws, SM, and Haff, GG. Effect of fitness level on time course of recovery after acute strength and high-intensity interval training. J Strength Cond Res XX(X): 000-000, 2024-The aim was to investigate time course of recovery after acute bouts of strength (STR) and high-intensity interval training (HIIT).

Validity and Inter-Device Reliability of an Artificial Intelligence App for Real-Time Assessment of 505 Change of Direction Tests.

The present study aimed to explore the validity and inter-device reliability of a novel artificial intelligence app (Asstrapp) for real-time measurement of the traditional (tra505) and modified-505 (mod505) change of direction (COD) tests. Twenty-five male Sports Science students (age, 23.5 ± 3.

Iron Deficiency Anaemia in a Stable Chronic Intestinal Failure Cohort: Prevalence, Associations and Outcomes.

Background & Aims: Current estimates of the prevalence of iron deficiency anaemia (IDA) in patients with chronic intestinal failure (CIF) exceed those seen in general population, however, the studies to-date are limited with relatively small numbers of patients. The aim of the study was to determine the point prevalence of IDA in a large cohort of stable HPN-dependent adults managed by a specialist Intestinal Failure Unit.

Methods: This was a retrospective cohort study of HPN-dependent adults managed by a national UK IF Reference Centre between 01/01/2019 and 31/12/2019.

Targeting P21-Activated Kinase 2 as a Novel Therapeutic Approach to Mitigate Endoplasmic Reticulum Stress in Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is linked to prolonged endoplasmic reticulum (ER) stress. P21-activated kinase 2 (Pak2) facilitates a protective ER stress response. This study explores the mechanism and role of Pak2 in HFpEF pathology.

Time to consider health services dedicated for adults living with cerebral small vessel disease: Report of a ESO scientific seminar.

Purpose: Cerebral small vessel disease (cSVD) is a highly prevalent disorder leading to physical, cognitive and functional decline. We report key barriers in the management of individuals with cSVD, the potential benefit of cSVD-dedicated health services, and evidence from existing models of care for adults with cSVD.

Methods: We examined information from a scientific seminar developed between seven experts in cSVD during the eighth European Stroke Organisation Conference that discussed the optimal health care for adults with cSVD and what health services dedicated to cSVD should include.

Evidence for targeting autonomic dysfunction in systemic sclerosis: A scoping review.

Autonomic dysfunction is a common and early complication among patients with systemic sclerosis, suggesting that it may play a role in the pathogenesis of the disease and be a potential target for therapeutic interventions. Although the true prevalence of autonomic dysfunction among patients with systemic sclerosis is still unclear, it is estimated that as many as 80% of patients may be affected. Autonomic dysfunction may lead to widespread multi-organ dysfunction through its effects on the cardiovascular system, gastrointestinal tract, urinary tract, sweat and salivary glands, and pupils.

Mosquitoes Reared in Nearby Insectaries at the Same Institution Have Significantly Divergent Microbiomes.

The microbiome influences critical aspects of mosquito biology and variations in microbial composition can impact the outcomes of laboratory studies. To investigate how biotic and abiotic conditions in an insectary affect the composition of the mosquito microbiome, a single cohort of Aedes aegypti eggs was divided into three batches and transferred to three different climate-controlled insectaries within the Liverpool School of Tropical Medicine. The bacterial microbiome composition was compared as mosquitoes developed, the microbiome of the mosquitoes' food sources was characterised, environmental conditions over time in each insectary were measured, and mosquito development and survival were recorded.

Geochemical insights into plant uptake of Technology-critical elements: A case study on lettuce from European soils.

While vegetable uptake of traditional metal contaminants is a well-studied pathway to human exposure and risk, a paucity of information exists on the uptake of emerging metal contaminants. This study evaluated the uptake of the Technology-critical elements (TCEs) gallium (Ga), germanium (Ge), niobium (Nb), tantalum (Ta), thallium (Tl), and rare earth elements (REEs) into lettuce cultivated in 21 European urban soils. For comparison, the uptake of cadmium (Cd) was also analysed.

Multimorbidity clusters and their associations with health-related quality of life in two UK cohorts.

Background: Identifying clusters of multiple long-term conditions (MLTCs), also known as multimorbidity, and their associated burden may facilitate the development of effective and cost-effective targeted healthcare strategies. This study aimed to identify clusters of MLTCs and their associations with long-term health-related quality of life (HRQoL) in two UK population-based cohorts.

Methods: Age-stratified clusters of MLTCs were identified at baseline in UK Biobank (n = 502,363, 54.

Skin adaptation in lower limb amputees assessed through Raman spectroscopy and mechanical characterization.

Following lower limb amputation residuum skin from the lower leg is used to reconstruct the residual limb. Unlike skin on the sole of the foot (plantar skin), leg skin is not inherently load bearing. Despite this, leg skin is required to be load bearing in the prosthetic socket.

Turning Cancer Immunotherapy to the Emerging Immune Checkpoint TIGIT: Will This Break Through the Limitations of the Legacy Approach?

The discovery of immune checkpoints (ICs) has pushed cancer treatment into the next era. As an emerging immune checkpoint, the TIGIT/CD155 axis inhibits the cytotoxicity of T and NK cells through multiple pathways. Immune checkpoint inhibitors (ICIs) targeting TIGIT are hopefully expected to address the issue of unresponsiveness to anti-PD-(L)1 monoclonal antibodies (mAbs) by combination therapy.

The Relationship Between Daily Activity Level, Posture Distribution, Stepping Patterns, and Cadence in the BCS70 Cohort.

This study investigated the relationship between stepping-defined daily activity levels, time spent in different postures, and the patterns and intensities of stepping behaviour. Using a thigh-mounted triaxial accelerometer, physical activity data from 3547 participants with seven days of valid data were analysed. We classified days based on step count and quantified posture and stepping behaviour, distinguishing between indoor, community, and recreation stepping.

Effects of 1-1,2,3-Triazole Derivatives of 3--Acetyl-11-Keto-Beta-Boswellic Acid from Resin on T-Cell Proliferation and Activation.

3--acetyl-11-keto--boswellic acid (-AKBA), a triterpene natural product, is one of the main natural products of resin (BSR) and has reported biological and immunomodulatory effects. 1-1,2,3-triazole derivatives of -AKBA (named -) were synthesized from -AKBA. The 1-1,2,3-triazole compounds are also known to have a wide range of biological and pharmacological properties as demonstrated by in vitro and in vivo studies.

ALDH Breast Cancer Stem Cells Exhibit a Mesenchymal-Senescent Hybrid Phenotype, with Elevated Metabolic and Migratory Activities.

Cancer stem cells (CSCs) account for 0.01 to 2% of the total tumor mass; however, they play a key role in tumor progression, metastasis and resistance to current cancer therapies. The generation and maintenance of CSCs are usually linked to the epithelial-mesenchymal transition (EMT), a dynamic process involved in reprogramming cancer cells towards a more aggressive and motile phenotype with increased stemness potential.

Sexual Health, Pleasure, Justice, and Well-Being in People With Rheumatic and Musculoskeletal Diseases: A Scoping Review Protocol.

Introduction: Sexual health, pleasure, justice (equity in sexual rights and experiences), and well-being are crucial determinants of health and life quality, yet often overlooked in the rheumatic and musculoskeletal diseases (RMD) field. However, this topic has received more attention recently, and there is a need to map the current literature to inform the direction of future studies. Hence, this protocol outlines a scoping review to systematically map existing evidence on sexual health in people with RMD, exploring key themes and identifying evidence gaps across multiple dimensions, including sexual well-being, justice and pleasure.

Computational modeling design of novel NMDAR agonist for the treatment of Schizophrenia.

Schizophrenia (SZ) is a complex, chronic mental disorder characterized by positive symptoms (such as delusions and hallucinations), negative symptoms (including anhedonia, alogia, avolition, and social withdrawal), and cognitive deficits (affecting attention, processing speed, verbal and visuospatial learning, problem-solving, working memory, and mental flexibility). Extensive animal and clinical studies have emphasized the NMDAR hypofunction hypothesis of SZ. Glycine plays a crucial role as an agonist of NMDAR, enhancing the receptor's affinity for glutamate and supporting normal synaptic function and plasticity, that is, signal transmission between neurons.

Effects of a priming session with heavy sled pushes on neuromuscular performance and perceived recovery in soccer players: a crossover design study during competitive microcycles.

This study compared the effects of a sled push priming session on performance in 20 m sprint times, vertical jump, and perceived recovery, in comparison to a control condition, during competitive microcycles. Sixteen young semi-professional football players completed two conditions: priming (heavy sled pushes and MD-1 training) and control (only MD-1 regular training), in a crossover design. Twenty-metre sprint times and countermovement jump (CMJ) were assessed 24 hours following the completion of the experimental sessions.