Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Airway tryptase levels inform the lack of clinical efficacy of the tryptase inhibitor MTPS9579A in asthma.

Background: Tryptase, a mast cell protease, has been identified as a potential therapeutic target in managing patients with refractory asthma. We assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of MTPS9579A, an anti-tryptase antibody, in a phase 2a randomized trial for patients with uncontrolled asthma and a phase 1c trial to understand activity within the lower respiratory tract.

Methods: Phase 2a patients (n = 134) received 1800 mg MTPS9579A or placebo intravenously every 4 weeks for 48 weeks.

FOXP4 Is a Direct YAP1 Target That Promotes Gastric Cancer Stemness and Drives Metastasis.

The Hippo-YAP1 pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration. Dysregulation of Hippo-YAP1 signaling promotes initiation and progression of several types of cancer, including gastric cancer. As the Hippo-YAP1 pathway regulates expression of thousands of genes, it is important to establish which target genes contribute to the oncogenic program driven by YAP1 to identify strategies to circumvent it.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

Background And Aim: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer.

Buying time! VA-ECMO as a bridge to successful reoperative cardiac surgery in a case of traumatic tricuspid valve injury.

Cardiac surgery performed on patients in cardiogenic shock is associated with a high mortality and morbidity. Preoperative Extra Corporeal Membrane Oxygenation (ECMO) in cardiogenic shock gives critically-ill patients a chance for surgical intervention and is associated with better surgical outcomes. We present a 29-year-old male who had a ventricular septal defect closure as a child and presented with multi-organ injuries following polytrauma.

Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.

The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined.

Incidence and prevalence of generalized pustular psoriasis in multiethnic Johor Bahru, Malaysia: a population-based cohort study using routinely captured electronic health records in the Teleprimary Care (TPC®) clinical information system from 2010 to 2020.

Background: There is limited understanding of the epidemiology of generalized pustular psoriasis (GPP) internationally, with no population-based estimates of GPP in South East Asia.

Objectives: To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors.

Methods: We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020.

Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.

Aims: Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse.

PK/PD modeling to characterize placebo and treatment effect of omalizumab for chronic spontaneous urticaria.

The pharmacokinetic (PK) characteristics of omalizumab and its pharmacodynamic (PD) effect in patients has yet to be fully characterized in chronic spontaneous urticaria, which could elucidate its pathogenesis and treatment response. This study has two objectives; (1) characterize the population PK of omalizumab and its PD effect on IgE, and (2) develop a drug effect model of omalizumab in urticaria (via change in weekly itch severity score). The target-mediated population of PK/PD model incorporating omalizumab-IgE binding and turnover adequately described PK and PD of omalizumab.

Clinical profile of patients with acute generalized pustular psoriasis with and without IL36RN mutations in multi-ethnic Johor Bahru, Malaysia.

Generalized Pustular psoriasis (GPP), a rare and potentially life-threatening auto-inflammatory disease, is associated with IL36RN mutations. Here, we analyse the prevalence of IL36RN mutations in our multi-ethnic GPP cohort and assess differences in the clinical profile of patients with (IL36RN-positive) and without (IL36RN-negative) mutations. IL36RN mutations were present in 17.

Clinical characteristics, management, and quality of life of psoriasis patients with coexistent lupus erythematosus: Data from the Malaysian Psoriasis Registry.

Objective: To describe the clinical characteristics, management and quality of life of psoriasis patients with and without coexistent lupus erythematosus (LE).

Methods: This retrospective cross-sectional study uses data from the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018.

Results: Of 21 735 psoriasis patients, 34 (0.

Cancer-associated fibroblasts potentiate colorectal cancer progression by crosstalk of the IGF2-IGF1R and Hippo-YAP1 signaling pathways.

Colorectal cancer (CRC) is one of the most common cancers worldwide. The tumor microenvironment exerts crucial effects in driving CRC progression. Cancer-associated fibroblasts (CAFs) serve as one of the most important tumor microenvironment components promoting CRC progression.

Targeting the Hippo Pathway in Gastric Cancer and Other Malignancies in the Digestive System: From Bench to Bedside.

The Hippo pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration under physiological conditions, and its aberrations have been well studied to promote tumor initiation and progression. Dysregulation of the Hippo tumor suppressor signaling frequently occurs in gastric cancer (GC) and other solid tumors and contributes to cancer development through modulating multiple aspects, including cell proliferation, survival, metastasis, and oncotherapy resistance. In the clinic, Hippo components also possess diagnostic and prognostic values for cancer patients.

Magnetic field therapy enhances muscle mitochondrial bioenergetics and attenuates systemic ceramide levels following ACL reconstruction: Southeast Asian randomized-controlled pilot trial.

Background: Metabolic disruption commonly follows Anterior Cruciate Ligament Reconstruction (ACLR) surgery. Brief exposure to low amplitude and frequency pulsed electromagnetic fields (PEMFs) has been shown to promote and murine myogeneses via the activation of a calcium-mitochondrial axis conferring systemic metabolic adaptations. This randomized-controlled pilot trial sought to detect local changes in muscle structure and function using MRI, and systemic changes in metabolism using plasma biomarker analyses resulting from ACLR, with or without accompanying PEMF therapy.

High-speed, large dynamic range spectral domain interrogation of fiber-optic Fabry-Perot interferometric sensors.

We report high-speed, large dynamic range spectral domain interrogation of fiber-optic Fabry-Perot (FP) interferometric sensors. An optical interrogation system employing a piezoelectric FP tunable filter and an array of fiber-Bragg gratings for wavelength referencing is developed to acquire the reflection spectrum of FP sensors at a high interrogation speed with a wide wavelength range. A 98 nm wavelength interrogation range was obtained at the resonance frequency of ∼110 of the FP tunable filter.

Structure of the core human NADPH oxidase NOX2.

NOX2 is the prototypical member of the NADPH oxidase NOX superfamily and produces superoxide (O), a key reactive oxygen species (ROS) that is essential in innate and adaptive immunity. Mutations that lead to deficiency in NOX2 activity correlate with increased susceptibility to bacterial and fungal infections, resulting in chronic granulomatous disease. The core of NOX2 is formed by a heterodimeric transmembrane complex composed of NOX2 (formerly gp91) and p22, but a detailed description of its structural architecture is lacking.

Out of the cycle: Impact of cell cycle aberrations on cancer metabolism and metastasis.

The use of cell cycle inhibitors has necessitated a better understanding of the cell cycle in tumor biology to optimize the therapeutic approach. Cell cycle aberrations are common in cancers, and it is increasingly acknowledged that these aberrations exert oncogenic effects beyond the cell cycle. Multiple facets such as cancer metabolism, immunity and metastasis are also affected, all of which are beyond the effect of cell proliferation alone.

Incidence and prevalence of psoriasis in multiethnic Johor Bahru, Malaysia: a population-based cohort study using electronic health data routinely captured in the Teleprimary Care (TPC®) clinical information system from 2010 to 2020: Classification: Epidemiology.

Background: There are no population-based epidemiological data on psoriasis in Southeast Asia, including Malaysia.

Objectives: To determine the incidence and prevalence of psoriasis over 11 years in multiethnic Johor Bahru, Malaysia.

Methods: A population-based cohort study was made using the Teleprimary Care database between January 2010 and December 2020.

Cancer-associated fibroblasts in nonsmall cell lung cancer: From molecular mechanisms to clinical implications.

Lung cancer is the common and leading cause of cancer death worldwide. The tumor microenvironment has been recognized to be instrumental in tumorigenesis. To have a deep understanding of the molecular mechanism of nonsmall cell lung carcinoma (NSCLC), cancer-associated fibroblasts (CAFs) have gained increasing research interests.

The Treatment Landscape of Advanced Hepatocellular Carcinoma.

The systemic treatment of advanced hepatocellular carcinoma (HCC) has significantly evolved. Immune checkpoint inhibitors (ICIs) have demonstrated clinical efficacy and more favorable toxicity profiles compared to multikinase inhibitors. Combination therapy with ICIs may provide greater anti-tumor activity compared to ICI monotherapy.

Management of mitral stenosis: a systematic review of clinical practice guidelines and recommendations.

A number of guidelines exist with recommendations for diagnosis and management of mitral stenosis (MS). We systematically reviewed existing guidelines for diagnosis and management of MS, highlighting their similarities and differences, in order to guide clinical decision-making. We searched national and international guidelines in MEDLINE and EMBASE (5/4/2011-5/9/2021), the Guidelines International Network, Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, and websites of relevant organizations.