Digital Inclusion in a Scottish National Pulmonary Hypertension Population.

To evaluate current digital inclusion in the Scottish pulmonary hypertension population, a paper questionnaire was offered to the entirety of patients with pulmonary arterial hypertension in Scotland. The Scottish Index of Multiple Deprivation was used to stratify patients into deprivation deciles. 464 patients returned questionnaires (86%).

Loss of STIM2, but not of STIM1, drives colorectal cancer metastasis through metabolic reprogramming and the ATF4 ER stress pathway.

The large amounts of calcium (Ca) stored in the endoplasmic reticulum (ER) and the controlled release of this Ca store into the cytosol regulate many cellular functions, and altered ER Ca homeostasis induces ER stress. Stromal-interacting molecules 1 and 2 (STIM1/2) are homologous ER-resident Ca sensors that synergistically activate cytosolic Ca influx through Orai channels to promote Ca-dependent changes in gene expression and ER Ca refilling. Here, we demonstrated that reduced abundance of STIM2, but not that of STIM1, was associated with poor prognosis in colorectal cancer (CRC).

The geometry of life: testing the scaling of whole-organism surface area and volume using sharks.

The ratio of surface area to volume is a key biological parameter that underpins our understanding of physiology across all levels of biological organization. Surfaces control the rate of key reactions and processes operating within the body and between organisms and their environment. Our understanding of surface area to volume ratios is embedded in the 2/3 scaling law, stating that surface area scales with volume raised to a power of 0.

Optimization of 3D Extrusion-Printed Particle-Containing Hydrogels for Osteogenic Differentiation.

There is a continued increase in demand for novel bone grafting substitutes to reduce reliance on and address challenges associated with allograft and autograft bone grafts. Current synthetic bone grafting substitutes exhibit low mechanical strength and bioactivity, which has inspired the development of novel grafting materials. Accelerating the translation of new bone graft substitutes requires workflows for high-throughput fabrication and analysis of particle-containing models.

Population Pharmacokinetics of Osimertinib in Patients With Non-Small Cell Lung Cancer.

Population pharmacokinetics (popPK) modeling for osimertinib, a third-generation, irreversible, oral epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitizing mutations and EGFR T790M, was previously reported utilizing AURA and AURA2 data (advanced non-small cell lung cancer [NSCLC]). We report updated popPK modeling incorporating AURA3 and FLAURA data (advanced NSCLC); model validation used ADAURA data (resected stage IB-IIIA NSCLC). Updated popPK analyses were based on patients from AURA (n = 599), AURA2 (n = 210), AURA3 (n = 277), and FLAURA (n = 278) using a linear one-compartmental disposition model for osimertinib and its metabolite, AZ5104, with first-order oral absorption.

Applying 3D Models of Giant Salamanders to Explore Form-Function Relationships in Early Digit-Bearing Tetrapods.

Extant salamanders are used as modern analogs of early digit-bearing tetrapods due to general similarities in morphology and ecology, but the study species have been primarily terrestrial and relatively smaller when the earliest digit-bearing tetrapods were aquatic and an order of magnitude larger. Thus, we created a 3D computational model of underwater walking in extant Japanese giant salamanders (Andrias japonicus) using 3D photogrammetry and open-access graphics software (Blender) to broaden the range of testable hypotheses about the incipient stages of terrestrial locomotion. Our 3D model and software protocol represent the initial stages of an open-access pipeline that could serve as a "one-stop-shop" for studying locomotor function, from creating 3D models to analyzing the mechanics of locomotor gaits.

Sustainably cultured coral scaffold supports human bone marrow mesenchymal stromal cell osteogenesis.

The current gold standard grafting material is autologous bone due to its osteoinductive and osteoconductive properties. Autograft harvesting results in donors site morbidity. Coral scaffolds offer a natural autograft alternative, sharing the density and porosity of human bone.

Sendaway capillary NT-proBNP in pulmonary hypertension.

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac ventricular wall stress that is incorporated into pulmonary hypertension (PH) risk stratification models. Sendaway sampling may enable patients to perform NT-proBNP tests remotely. This UK-wide study aimed to assess the agreement of sendaway NT-proBNP with standard venous NT-proBNP and to assess the effect of delayed processing.

In vitro PK/PD modeling of tyrosine kinase inhibitors in non-small cell lung cancer cell lines.

Tyrosine kinase inhibitors (TKIs) are routinely prescribed for the treatment of non-small cell lung cancer (NSCLC). As with all medications, patients can experience adverse events due to TKIs. Unfortunately, the relationship between many TKIs and the occurrence of certain adverse events remains unclear.

Pulmonary Embolism (PE) to Chronic Thromboembolic Pulmonary Disease (CTEPD): Findings from a Survey of UK Physicians.

Chronic thromboembolic pulmonary disease (CTEPD) is a complication of pulmonary embolism (PE). We conducted an online survey of UK PE-treating physicians to understand practices in the follow-up of PE and awareness of CTEPD. The physicians surveyed ( = 175) included 50 each from cardiology, respiratory and internal medicine, plus 25 haematologists.

Remote exercise testing in pulmonary hypertension (PHRET).

Remote exercise tests for patients with pulmonary hypertension (PH) would improve the telemedicine strategies in this disease. The PHRET study assessed the validity and feasibility of four remote exercise tests performed by PH patients at home. Participants undergoing diagnostic assessment for PH were included.

Study of heart function in PRE-Eclampsia during and after PreGnancy (SHePREG): The pilot cohort.

Background: Pre-eclampsia with severe features (severe PreE) is associated with heart dysfunction, yet the impact beyond pregnancy, including its association with cardiomyopathic genetic polymorphisms, remains poorly understood.

Objective: We aimed to characterize the temporal impact of severe PreE on heart function through the 4th trimester in women with and without deleterious cardiomyopathic genetic variants.

Methods: Pregnant women were enrolled to undergo transthoracic echocardiography (TTE) in late pregnancy and 3 months postpartum.

The History of Flow Chemistry at Eli Lilly and Company.

Flow chemistry was initially used for speed to early phase material delivery in the development laboratories, scaling up chemical transformations that we would not or could not scale up batch for safety reasons. Some early examples included a Newman Kwart Rearrangement, Claisen rearrangement, hydroformylation, and thermal imidazole cyclization. Next, flow chemistry was used to enable safe scale up of hazardous chemistries to manufacturing plants.

Longitudinal Circulating Tumor DNA Modeling to Predict Disease Progression in First-Line Mutant Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer.

This exploratory, post hoc analysis aimed to model circulating tumor DNA (ctDNA) dynamics and predict disease progression in patients with treatment-naïve locally advanced/metastatic epidermal growth factor receptor mutation (EGFRm)-positive non-small cell lung cancer, from the FLAURA trial (NCT02296125). Patients were randomized 1:1 and received osimertinib 80 mg once daily (q.d.

Management of trigeminal neuralgia: A multi-centre case study in general practice.

Background And Aims: Patients often first present with symptoms of trigeminal neuralgia (TN) to primary care. However, there has been little research to determine whether the diagnosis and management of this condition is carried out according to current guidelines. Furthermore, there is little up-to-date information regarding the prevalence of TN in the UK.

Loss of STIM2 in colorectal cancer drives growth and metastasis through metabolic reprogramming and PERK-ATF4 endoplasmic reticulum stress pathway.

The endoplasmic reticulum (ER) stores large amounts of calcium (Ca), and the controlled release of ER Ca regulates a myriad of cellular functions. Although altered ER Ca homeostasis is known to induce ER stress, the mechanisms by which ER Ca imbalance activate ER stress pathways are poorly understood. Stromal-interacting molecules STIM1 and STIM2 are two structurally homologous ER-resident Ca sensors that synergistically regulate Ca influx into the cytosol through Orai Ca channels for subsequent signaling to transcription and ER Ca refilling.

Retrospective Data Analysis of the Use of an Autologous Multilayered Leukocyte, Platelet, and Fibrin Patch for Diabetic Foot Ulcers Treatment in Daily Clinical Practice.

Objective: To describe the healing outcome of chronic, hard-to-heal diabetic foot ulcers (DFUs) treated with an autologous multilayered leukocyte, platelet, and fibrin (MLPF) patch in addition to the best standard of care, in a real-world clinical setting of two US amputation preventive centers.

Methods: In this retrospective study of patients treated between September 2021 and October 2022, the authors analyzed DFU healing outcomes based on Wound, Ischemia, and foot Infection-derived amputation risk.

Results: All 36 patients had a diagnosis of type 2 diabetes and 29 (81%) were male.

Predictors of outcomes in mild pulmonary hypertension according to 2022 ESC/ERS Guidelines: the EVIDENCE-PAH UK study.

Background And Aims: Interventional studies in pulmonary arterial hypertension completed to date have shown to be effective in symptomatic patients with significantly elevated mean pulmonary artery pressure (mPAP) (≥25 mmHg) and pulmonary vascular resistance (PVR) > 3 Wood Unit (WU). However, in health the mPAP does not exceed 20 mmHg and PVR is 2 WU or lower, at rest. The ESC/ERS guidelines have recently been updated to reflect this.

The MRC Dyspnoea Scale and mortality risk prediction in pulmonary arterial hypertension: A retrospective longitudinal cohort study.

Risk stratification models in pulmonary arterial hypertension (PAH) rely on World Health Organisation Functional Class (WHO FC). A high proportion of patients are classified as WHO FC III, a heterogenous group which limits the stratification abilities of risk models. The Medical Research Council (MRC) Dyspnoea Scale may allow a more precise assessment of functional status and improve current risk models.

Quantitative Global Survey Results of Acute Back Pain Sufferers Across Four Countries.

Background: Surveys of back pain sufferers in the United States, China, Russia, and Germany were performed to better understand self-reported causes of acute nonspecific back pain and acute lower back pain among individuals engaging in sports and their preferred treatments.

Methods: In each country, 1000 participants were surveyed (Step 1) to identify a population of nonspecific acute back pain sufferers, understand pain and treatment characteristics, and generate profiles for individuals with long-lasting (≥7 days) acute lower back pain. Subsequently, 200 participants with acute lower back pain episodes (7-21 days) and sports participation were identified in each country and completed surveys (Step 2) about sociodemographic, pain, treatment characteristics, and causes/triggers of long-lasting acute lower back pain episodes.

Attitudes to Male Homosexuality Within the British Medical Association in the 1950s.

The British Government appointed a departmental committee to review anti-homosexuality laws in 1954 following a marked increase in the number of arrests for homosexuality after World War II. The committee invited the British Medical Association (BMA) and other institutions to provide scientific and medical evidence relating to homosexuality. In 1954, the BMA established the Committee on Homosexuality and Prostitution to present its view on how the law impacted upon homosexuals and society.