Developing Allosteric Chaperones for -Associated Disorders-An Integrated Computational and Experimental Approach.

Mutations in the gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are associated with Gaucher disease and increased risk of Parkinson's disease. This study describes the discovery and characterization of novel allosteric pharmacological chaperones for GCase through an innovative computational approach combined with experimental validation. Utilizing virtual screening and structure-activity relationship optimization, researchers identified several compounds that significantly enhance GCase activity and stability across various cellular models, including patient-derived fibroblasts and neuronal cells harboring mutations.

Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively.

Pilot study to evaluate isolation by size of circulating tumour cells in canine oral melanoma.

Liquid biopsy for circulating tumour cell (CTC) detection is generally unexplored in veterinary medicine. Dogs with highly aggressive and heterogeneous tumours, such as oral malignant melanoma (OMM), could benefit from studies involving size-based isolation methods for CTCs, as they do not depend on specific antibodies. This pilot study aimed to detect CTCs from canine OMM using Isolation by Size of Epithelial Tumor Cells (ISET), a microfiltration methodology, followed by immunocytochemistry (ICC) with Melan-A, PNL2, and S100 antibodies.

Discovery of allosteric regulators with clinical potential to stabilize alpha-L-iduronidase in mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal disease caused by lowered activity of the enzyme alpha-L-iduronidase (IDUA). Current therapeutic options show limited efficacy and do not treat some important aspects of the disease. Therefore, it may be advantageous to identify strategies that could improve the efficacy of existing treatments.

From home energy management systems to energy communities: methods and data.

This paper introduces the HEMStoEC database, which contains data recorded in the course of two research projects, NILMforIHEM , and HEMS2IEA , for more than three years. To be manageable, the dataset is divided in months, from January 2020 until February 2023. It consists in: (a) consumption electric data for four houses in a neighbourhood situated in the south of Portugal, (b) weather data for that location, (c) photovoltaic and battery data, (d) inside climate data, and (e) operation of several electric devices in one of the four houses.

The Cardiovascular Event Risk Associated with Tyrosine Kinase Inhibitors and the Lipid Profile in Patients with Chronic Myeloid Leukemia.

Background: Second- and third-generation tyrosine kinase inhibitors (TKIs) are now available to treat chronic-phase chronic myeloid leukemia (CP-CML) in the first and second line. However, vascular adverse events (VAEs) have been reported for patients with CML treated with some TKIs.

Methods: We retrospectively evaluated the cumulative incidence (CI) and cardiovascular risk for 210 patients included in the Canarian Registry of CML.

Validation of a highly sensitive HaloTag-based assay to evaluate the potency of a novel class of allosteric β-Galactosidase correctors.

Site-directed Enzyme Enhancement Therapy (SEE-Tx®) technology is a disease-agnostic drug discovery tool that can be applied to any protein target of interest with a known three-dimensional structure. We used this proprietary technology to identify and characterize the therapeutic potential of structurally targeted allosteric regulators (STARs) of the lysosomal hydrolase β-galactosidase (β-Gal), which is deficient due to gene mutations in galactosidase beta 1 (GLB1)-related lysosomal storage disorders (LSDs). The biochemical HaloTag cleavage assay was used to monitor the delivery of wildtype (WT) β-Gal and four disease-related β-Gal variants (p.

Circulating tumor cells as a predictor and prognostic tool for metastatic clear cell renal carcinoma: An immunocytochemistry and genomic analysis.

Background: Treatment of metastatic clear cell renal carcinoma (mccRCC) has changed dramatically over the past 20 years, without improvement in the development of biomarkers. Recently, circulating tumor cells (CTCs) have been validated as a prognostic and predictive tool for many solid tumors.

Objective: We evaluated CTCs in blood samples obtained from patients diagnosed with mccRCC.

Clinicopathologic Features of 2018 American Society of Clinical Oncology/College of American Pathologists Fluorescence In Situ Hybridization Group 3 Breast Carcinoma (Human Epidermal Growth Factor Receptor 2 Chromosome 17 Centromere Ratio <2.0 and Average Human Epidermal Growth Factor Receptor 2 Copy Number ≥6.0).

Context.—: The American Society of Clinical Oncology/College of American Pathologists 2018 update of the human epidermal growth factor receptor 2 (HER2) testing guideline includes a fluorescence in situ hybridization (FISH) group with a HER2 to chromosome 17 centromere (CEP17) ratio less than 2.0 and HER2 copy number 6.

Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.

Objectives: Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC.

Methods: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015.

CD47 Expression in Circulating Tumor Cells and Circulating Tumor Microemboli from Non-Small Cell Lung Cancer Patients Is a Poor Prognosis Factor.

Unlabelled: Circulating tumor cells (CTCs) and/or circulating tumor microemboli (CTM) from non-small cell lung cancer (NSCLC) patients may be a non-invasive tool for prognosis, acting as liquid biopsy. CTCs interact with platelets through the transforming growth factor-β/transforming growth factor-β receptor type 1 (TGF-β/TGFβRI) forming clusters. CTCs also may express the Cluster of Differentiation 47 (CD47) protein, responsible for the inhibition of phagocytosis, the "don't eat me" signal to macrophages.

Quantitative Imaging Analysis Fluorescence In Situ Hybridization Validation for Clinical HER2 Testing in Breast Cancer.

Context.—: Quantitative imaging is a promising tool that is gaining wide use across several areas of pathology. Although there has been increasing adoption of morphologic and immunohistochemical analysis, the adoption of evaluation of fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue has been limited because of complexity and lack of practice guidelines.

Has the COVID-19 pandemic changed the clinical picture and tumour stage at the time of presentation of patients with colorectal cancer? A retrospective cohort study.

Introduction: Treatment of patients with Coronavirus Disease 2019 (COVID-19) has affected the management of patients with colorectal cancer (CRC). The aim of this study was to compare the diagnosis delay, symptoms, and stage of patients with CRC during the pandemic with a control cohort.

Material And Methods: Patients referred to the CRC multidisciplinary team between September 2019 and January 2020 (cohort 1, control group) were compared with those who presented between September 2020 and March 2021 (cohort 2, pandemic group).

HPV virus and biomarkers of resistance to chemoradiation in circulating tumor cells from patients with squamous cell carcinoma of the anus.

Unlabelled: Localized anal cancer is mostly represented by squamous cell carcinoma of the anus (SCCA) and is cured in ≥80 % of cases by chemoradiation (CRT). Development of techniques for detection/evaluating circulating tumor cells (CTCs) for diagnosis/ prognosis/response to therapy can change the manner we treat/follow SCCA patients.

Objective: to detect CTCs from patients with SCCA and evaluate the presence of HPV virus, p16 expression and markers related to resistance to CRT (RAD23B/ ERCC1/ TYMS) in CTCs at baseline and after CRT.

Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma.

Cancer is primarily a disease in which late diagnosis is linked to poor prognosis, and unfortunately, detection and management are still challenging. Circulating tumor cells (CTCs) are a potential resource to address this disease. Cell fusion, an event discovered recently in CTCs expressing carcinoma and leukocyte markers, occurs when ≥2 cells become a single entity (hybrid cell) after the merging of their plasma membranes.

A comprehensive review of solar irradiation estimation and forecasting using artificial neural networks: data, models and trends.

Solar irradiation data are imperatively required for any solar energy-based project. The non-accessibility and uncertainty of these data can greatly affect the implementation, management, and performance of photovoltaic or thermal systems. Developing solar irradiation estimation and forecasting approaches is an effective way to overcome these issues.

Total Shoulder Reverse Arthroplasty in Alkaptonuria: An Effective Option to Treat a Complication of a Rare Disease.

Introduction: Alkaptonuria (AKU) is a rare autosomal recessive disorder in which tyrosine metabolism is altered. There is a deficiency of the Homogentisate 1,2-dioxygenase enzyme (homogentisic acid oxidase) This enzyme is responsible for the metabolism of the tyrosine - homogentisic acid - in maleylacetoacetic acid. Accumulation of homogenous acid occurs in urine and conjunctival tissue in the second with important deleterious effects on cartilage and bone.

Design and validity of an instrument to assess healthcare professionals' perceptions, behaviour, self-efficacy and attitudes towards evidence-based health practice: I-SABE.

Objectives: To develop and validate an instrument to measure Brazilian healthcare professionals' perceptions, behaviour, self-efficacy and attitudes towards evidence-based health practice.

Design: Validation of an instrument using the Delphi method to ensure content validity and data from a cross-sectional survey to evaluate psychometric characteristics (psychometric sensitivity, factorial validity and reliability).

Setting: National Register of Health Establishments database.

How can we best help this patient? Exploring mental health therapists' reflections on medication-free care for patients with psychosis in Norway.

Background: Since 2015, Norwegian Regional Health Authorities have followed new government policy and gradually implemented medication-free services for patients with psychosis. The aim of this qualitative study was to explore the tension between policy and practice, and how health care workers in Bergen reflect on their role in implementing medication-free treatment.

Methods: We performed three focus group discussions including 17 therapists working within medication free services, asking about their experiences with this new treatment program.

Has the COVID-19 pandemic changed the clinical picture and tumour stage at the time of presentation of patients with colorectal cancer? A retrospective cohort study.

Introduction: Treatment of patients with Coronavirus Disease 2019 (COVID-19) has affected the management of patients with colorectal cancer (CRC). The aim of this study was to compare the diagnosis delay, symptoms, and stage of patients with CRC during the pandemic with a control cohort.

Material And Methods: Patients referred to the CRC multidisciplinary team between September 2019 and January 2020 (cohort 1, control group) were compared with those who presented between September 2020 and March 2021 (cohort 2, pandemic group).