Podiatric Clinical Triage in a Foot and Ankle Orthopaedic Clinic: A Randomised Trial.

Rationale: Hospitals are increasingly utilising allied-health professionals to provide clinical triage to patients. While these positions are routinely implemented, and several observational studies have reported positive outcomes, the effectiveness of this intervention has been rarely tested in a clinical trial.

Aims And Objectives: The objectives of this study were to (i) evaluate a podiatry-led orthopaedic triage service using patient-reported outcome measures (PROMs), and (ii) determine if it is cost-effective in terms of incremental cost/quality-adjusted life years (QALYs).

Sarc-Global: a new sarcopenia screening tool in older adults.

Background: Sarcopenia is associated with clinical complications that increase mortality in older adults. Current screening tools, such as Sarc-F and Sarc-CalF, focus primarily on muscular performance but have limited sensitivity in identifying elderly individuals at risk of sarcopenia. The present study aims to develop a more comprehensive sarcopenia risk screening tool, Sarc-Global, which integrates additional anthropometric and clinical variables to enhance the sensitivity and accuracy of sarcopenia risk assessment in older adults.

Cell non-autonomous signaling through the conserved C. elegans glycoprotein hormone receptor FSHR-1 regulates cholinergic neurotransmission.

Modulation of neurotransmission is key for organismal responses to varying physiological contexts such as during infection, injury, or other stresses, as well as in learning and memory and for sensory adaptation. Roles for cell autonomous neuromodulatory mechanisms in these processes have been well described. The importance of cell non-autonomous pathways for inter-tissue signaling, such as gut-to-brain or glia-to-neuron, has emerged more recently, but the cellular mechanisms mediating such regulation remain comparatively unexplored.

Cell non-autonomous signaling through the conserved glycopeptide hormone receptor FSHR-1 regulates cholinergic neurotransmission.

Modulation of neurotransmission is key for organismal responses to varying physiological contexts such as during infection, injury, or other stresses, as well as in learning and memory and for sensory adaptation. Roles for cell autonomous neuromodulatory mechanisms in these processes have been well described. The importance of cell non-autonomous pathways for inter-tissue signaling, such as gut-to-brain or glia-to-neuron, has emerged more recently, but the cellular mechanisms mediating such regulation remain comparatively unexplored.

Framework for implementing asylum seekers and refugees' health into the undergraduate medical curriculum in the United Kingdom.

The Ukrainian conflict and the increasing number of asylum seekers and refugees (AS&Rs) in the United Kingdom have highlighted the critical need for a dedicated AS&R health curriculum in medical undergraduate programmes. This study utilized a mixed-method approach to assess the current state of AS&R curricula worldwide, identify shortcomings in the UK's medical undergraduate curriculum and determine the specific needs of AS&R. A scoping review of literature revealed an absence of comprehensive AS&R health curricula, with many programmes focusing on broader global health issues.

The Properties and Domain Requirements for Phase Separation of the Sup35 Prion Protein In Vivo.

The Sup35 prion protein of budding yeast has been reported to undergo phase separation to form liquid droplets both at low pH in vitro and when energy depletion decreases the intracellular pH in vivo. It also has been shown using purified proteins that this phase separation is driven by the prion domain of Sup35 and does not re-quire its C-terminal domain. In contrast, we now find that a Sup35 fragment consisting of only the N-terminal prion domain and the M-domain does not phase separate in vivo; this phase separation of Sup35 requires the C-terminal domain, which binds Sup45 to form the translation termination complex.

Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis.

Glial cells and central nervous system (CNS)-infiltrating leukocytes contribute to multiple sclerosis (MS). However, the networks that govern crosstalk among these ontologically distinct populations remain unclear. Here, we show that, in mice and humans, CNS-resident astrocytes and infiltrating CD44CD4 T cells generated interleukin-3 (IL-3), while microglia and recruited myeloid cells expressed interleukin-3 receptor-ɑ (IL-3Rɑ).

Cluster-ID-Based Throughput Improvement in Cognitive Radio Networks for 5G and Beyond-5G IoT Applications.

Cognitive radio (CR), which is a common form of wireless communication, consists of a transceiver that is intelligently capable of detecting which communication channels are available to use and which are not. After this detection process, the transceiver avoids the occupied channels while simultaneously moving into the empty ones. Hence, spectrum shortage and underutilization are key problems that the CR can be proposed to address.

Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade.

Background: This phase 1b study (NCT02323191) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of colony-stimulating factor-1 receptor-blocking monoclonal antibody (mAb) emactuzumab in combination with the programmed cell death-1 ligand (PD-L1)-blocking mAb atezolizumab in patients with advanced solid tumors naïve or experienced for immune checkpoint blockers (ICBs).

Methods: Emactuzumab (500-1350 mg flat) and atezolizumab (1200 mg flat) were administered intravenously every 3 weeks. Dose escalation of emactuzumab was conducted using the 3+3 design up to the maximum tolerated dose (MTD) or optimal biological dose (OBD).

Active lifestyle enhances protein expression profile in subjects with Lewy body pathology.

Unlabelled: Clinical trials of the effects of physical activity have reported improvements in symptoms and quality of life in patients with Parkinson's disease (PD). Additionally, morphological brain changes after exercising were reported in PD animal models. However, these lifestyle-related changes were not evaluated in postmortem brain tissue.

Long-term clinical activity, safety and patient-reported quality of life for emactuzumab-treated patients with diffuse-type tenosynovial giant-cell tumour.

Objectives: This study investigated the safety, clinical activity and patient-reported outcomes of patients with diffuse-type tenosynovial giant-cell tumour (dTGCT) of the soft tissue who were treated with emactuzumab, a humanised anti-colony stimulating factor 1 receptor (CSF1R) monoclonal antibody and were followed up for up to 2 years after the start of treatment.

Methods: In this open-label phase 1 study (ClinicalTrials.govNCT01494688), patients received intravenous (IV) emactuzumab from 900 to 2000 mg every two weeks in the dose-escalation phase and at the optimal biological dose of 1000 mg with different schedules in the dose-expansion phase.

An SEM compatible plasma cell for in situ studies of hydrogen-material interaction.

An in situ hydrogen (H) plasma charging and in situ observation method was developed to continuously charge materials, while tensile testing them inside a scanning electron microscope (SEM). The present work will introduce and validate the setup and showcase an application allowing high-resolution observation of H-material interactions in a Ni-based alloy, Alloy 718. The effect of charging time and pre-straining was investigated.

Optimal professional development ICT training initiatives at flagship universities.

This study explores best practices and roles of information and communication technology (ICT) in select professional development centers at 16 flagship universities. Through adopting a qualitative case study design, this study explores the strengths and weaknesses of current technology training initiatives in the selected professional development centers. As part of the research and teaching programs at flagship universities, professional development center leaders shared about the current ICT practices as well as the strengths and limitations of their own centers.

Ventilator hyperinflation determined by peak airway pressure delivered: A randomized crossover trial.

Aim: The aim of this study was to see if a more sophisticated ventilator hyperinflation protocol might result in more sputum clearance compared to manual hyperinflation.

Background: Hyperinflation has been used to mobilize lung secretions in mechanically ventilated patients in the intensive care unit setting for almost 50 years. In the past decade, rather than using a bag external to the ventilator circuit to deliver hyperinflation (known as "bagging" or "manual hyperinflation"), a new technique has evolved using existing ventilator circuitry (known as "ventilator hyperinflation").

A phase Ib/II study of HER3-targeting lumretuzumab in combination with carboplatin and paclitaxel as first-line treatment in patients with advanced or metastatic squamous non-small cell lung cancer.

Purpose: This study investigated the safety and clinical activity of lumretuzumab, a humanised antihuman epidermal growth factor receptor 3 (HER3) monoclonal antibody, in combination with carboplatin and paclitaxel in first-line treatment of patients with squamous non-small cell lung cancer (sqNSCLC). HER3 ligand heregulin and HER3 protein expression were evaluated as potential biomarkers of clinical activity.

Patients And Methods: This open-label, phase Ib/II study enrolled patients receiving lumretuzumab at 800 mg (flat) in combination with carboplatin (area under the curve (AUC) 6 mg/mL×min) and paclitaxel (200 mg/m) administered intravenously on a every 3-week schedule.

Phase I study of emactuzumab single agent or in combination with paclitaxel in patients with advanced/metastatic solid tumors reveals depletion of immunosuppressive M2-like macrophages.

Background: Emactuzumab is a monoclonal antibody against the colony-stimulating factor-1 receptor and targets tumor-associated macrophages (TAMs). This study assessed the safety, clinical activity, pharmacokinetics (PK) and pharmacodynamics (PD) of emactuzumab, as monotherapy and in combination with paclitaxel, in patients with advanced solid tumors.

Patients And Methods: This open-label, phase Ia/b study comprised two parts (dose escalation and dose expansion), each containing two arms (emactuzumab, every 2 or 3 weeks, as monotherapy or in combination with paclitaxel 80 mg/m2 weekly).

SIESTA: A high current ion source for erosion and retention studies.

Second ion experiment for sputtering and TDS analysis is a high-current ion source for erosion and retention studies with focus on wall materials for fusion devices. The system is composed of a DuoPIGatron type ion source, three consecutive grids for ion extraction, acceleration and beam focusing, a differential pumping stage, a dipole magnet for mass filtering, a quadrupole doublet lens, a target chamber, a load-lock, and a chamber for thermal desorption spectrometry. The acceleration potential of the source can be varied between 500 V and 10 kV.

EGFR and HER3 signaling blockade in invasive mucinous lung adenocarcinoma harboring an NRG1 fusion.

Rearrangements of NRG1 have been identified in invasive mucinous adenocarcinoma of the lung (IMA), formerly referred to as mucinous bronchioloalveolar carcinoma. NRG1 ligand signals through induction of HER2-HER3 heterodimers, thus leading to PI3K-AKT pathway activation. Therefore, targeting HER2, HER3 and the downstream pathway may be a hypothesis-driven strategy for IMA with NRG1 fusion.

Clinical development of HER3-targeting monoclonal antibodies: Perils and progress.

The human epidermal growth factor receptor (HER) family consists of four transmembrane receptor tyrosine kinases: epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. They are part of a complex signalling network and stimulate intracellular pathways regulating cell growth and differentiation. So far, monoclonal antibodies (mAbs) and small molecule tyrosine kinase inhibitors targeting EGFR and HER2 have been developed and approved.

Mechanistic Investigations of Diarrhea Toxicity Induced by Anti-HER2/3 Combination Therapy.

Combination of targeted therapies is expected to provide superior efficacy in the treatment of cancer either by enhanced antitumor activity or by preventing or delaying the development of resistance. Common challenges in developing combination therapies include the potential of additive and aggravated toxicities associated with pharmacologically related adverse effects. We have recently reported that combination of anti-HER2 and anti-HER3 antibodies, pertuzumab and lumretuzumab, along with paclitaxel chemotherapy in metastatic breast cancer, resulted in a high incidence of diarrhea that ultimately limited further clinical development of this combination.

Thoracic aortic aneurysm complicated by secondary aortoesophageal fistula after thoracic endovascular aortic repair : a case report.

This is a case report of a patient with a thoracic aortic aneurysm (TAA) presenting with dysphagia and weight loss as primary symptoms. She was treated via thoracic endovascular aortic repair (TEVAR). The procedure was complicated with a secondary aortoesophageal fistula (AEF) for which open surgical repair of the esophageal defect was done.

Association between diabetes and causes of dementia: Evidence from a clinicopathological study.

Background: Diabetes mellitus is a risk factor for dementia, especially for vascular dementia (VaD), but there is no consensus on diabetes as a risk factor for Alzheimer's disease (AD) and other causes of dementia.

Objective: To explore the association between diabetes and the neuropathological etiology of dementia in a large autopsy study.

Methods: Data were collected from the participants of the Brain Bank of the Brazilian Aging Brain Study Group between 2004 and 2015.

Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer.

Unlabelled: Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m weekly in all cohorts).