Inhibition of IKK complex by (2 methyl butyryl) Shikonin, a naturally occurring naphthoquinone, abrogates melanoma growth and progression via modulation of the IKK/NFκB /EMT signaling axis.

Melanoma is an aggressive form of malignancy that originates from melanin-producing cells known as melanocytes underlying the basal layer of the epidermis with a poor prognosis, low survival rates, and limited treatment options. Although several specific and effective systematic strategies for treating melanoma have been established, the underlying molecular mechanism of melanoma progression, mortality and the promising therapeutic options remain elusive. Shikonin (SK), a natural naphthoquinone derived from a medicinal herbaceous plant, has been shown to inhibit the proliferation of several cancer cells.

The interaction of structured data using openEHR and large Language models for clinical decision support in prostate cancer.

Background: Multidisciplinary teams (MDTs) are essential for cancer care but are resource-intensive. Decision-making processes within MDTs, while critical, contribute to increased healthcare costs due to the need for specialist time and coordination. The recent emergence of large language models (LLMs) offers the potential to improve the efficiency and accuracy of clinical decision-making processes, potentially reducing costs associated with traditional MDT models.

Characteristics of patients with somatoform pain disorder.

Background: Patients with somatoform pain experience physical pain that cannot be attributed to any underlying medical or physiological cause, and it is often thought to be related to psychological factors. Health professionals encounter difficulties identifying this specific type of chronic pain, leading to suboptimal treatment strategies. Therefore, we aimed to describe the characteristics of patients with somatoform pain, to support the identification of affected patients.

Behind the scenes of EQA-characteristics, capabilities, benefits and assets of external quality assessment (EQA).

The main stakeholders in external quality assessment (EQA) programs are the participants, in whose interests these challenges are ultimately organised. EQA schemes in the medical field contribute to improving the quality of patient care by evaluating the analytical and diagnostic quality of laboratory and point-of-care tests (POCT) by independent third parties and, if necessary, pointing out erroneous measurement results and analytical or diagnostic improvement potential. Other benefits include the option of using EQA samples for other important laboratory procedures, such as the verification or validation of diagnostic medical devices (IVD-MDs), a contribution to the estimation of measurement uncertainty, a means of training and educating laboratory staff through educational EQA programmes or samples, or even for independent and documented monitoring of staff competence, such as on samples with unusual or even exceptional characteristics.

Standardization of hemoglobin A and hemoglobin F: Achievements and perspectives.

The establishment of reference systems for the standardization of hemoglobin A (HbA) and fetal hemoglobin (HbF), both critical for improving diagnostic accuracy in conditions such as β-thalassemia and sickle cell disease, are described. Efforts were led by the IFCC and other groups to address and reduce the variability in laboratory measurements of these hemoglobins. This document outlines the production of certified reference materials (CRMs) for HbA and the development of a reference measurement procedure using isotope dilution mass spectrometry.

ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation.

Objective: This study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with noncentral geographic atrophy (GA).

Design: ReCLAIM-2 was a prospective, phase II, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875).

Subjects: Patients aged ≥55 years with ≥1 eye with dry AMD with GA were enrolled.

Dual-energy CT of acute bowel ischemia-influence on diagnostic accuracy and reader confidence.

Objectives: This study evaluates the advantages in diagnostic accuracy, confidence, and reading time of additional dual-energy CT-derived reconstructions for assessing acute bowel ischemia.

Methods And Materials: This retrospective study includes 25 patients with surgically proven acute bowel ischemia and 25 gender- and age-matched controls who underwent biphasic abdominal dual-energy CT. Two fellowship-trained abdominal radiologists and two residents evaluated all cases with and without additional dual-energy CT-derived iodine maps and virtual non-contrast images.

Visual Loss in Geographic Atrophy: Learnings from the Lampalizumab Trials.

Purpose: To assess the correlation of lesion growth rate and baseline factors, including foveal involvement and focality, on visual loss as measured by best-corrected visual acuity (BCVA) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Design: Retrospective analysis of the lampalizumab phase 3 (NCT02247479 and NCT02247531) and prospective observational (NCT02479386) trials.

Participants: Patients with bilateral GA.

Imaging-Guided Classification of Neovascularization in Neovascular Age-Related Macular Degeneration: Progress to Date.

To review the evolution of terminology describing the classification of lesions in neovascular age-related macular degeneration (nAMD) based on retinal imaging technologies. A review of the current and historical literature on imaging-guided classification of neovascularization in nAMD was performed. Imaging-guided classification of neovascularization in nAMD facilitates understanding of the pathological mechanisms and disease progression.

ECM Proteins Nidogen-1 and Decorin Restore Functionality of Human Islets of Langerhans upon Hypoxic Conditions.

Transplantation of donor islets of Langerhans is a potential therapeutic approach for patients with diabetes mellitus; however, its success is limited by islet death and dysfunction during the initial hypoxic conditions at the transplantation site. This highlights the need to support the donor islets in the days post-transplantation until the site is vascularized. It was previously demonstrated that the extracellular matrix (ECM) proteins nidogen-1 (NID1) and decorin (DCN) improve the functionality and survival of the β-cell line, EndoC-βH3, and the viability of human islets post-isolation.

Making the effect visible - OX40 targeting nanobodies for imaging of activated T cells.

Purpose: Human OX40 (hOX40/CD134), a member of the TNF receptor superfamily, is mainly expressed on activated T lymphocytes. Triggered by its ligand OX40L (CD252), it provides costimulatory signals that support the differentiation, proliferation and long-term survival of T cells. Besides being a relevant therapeutic target, hOX40 is also an important biomarker for monitoring the presence or infiltration of activated T cells within the tumor microenvironment (TME), the inflammatory microenvironment (IME) in immune-mediated diseases (IMIDs) and the lymphatic organs.

MACULAR CHANGES IN ADULTS WITH HISTORY OF PREMATURE BIRTH.

Purpose: To characterize changes in the macular structure and vascularity seen in premature-birth adults.

Methods: Retrospective review of adult patients seen in the clinic from July 2018 to November 2020 with history of premature birth not requiring treatment for retinopathy of prematurity, as well as healthy controls. Swept-source ocular coherence tomography-angiography scans were analyzed for various parameters related to the macular structure and vascularity.

Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1.

To review the first Research and Safety in Therapeutics (ReST) Committee webinar and summarize the most current recommendations regarding diagnosis and management. The ReST Committee is comprised of members of the American Society of Retina Surgeons (ASRS). At regular internal meetings, safety issue reports from the website are reviewed.

New concept for control material in glucose point-of-care-testing for external quality assessment schemes.

Objectives: Until now, the external quality assessment (EQA) of glucose point-of-care testing (POCT) has lacked a high quality, suitable and commutable control material to assess measurement accuracy. Here we present a concept for determining the accuracy of glucose measurements, which uses human whole blood and does not require stabilising agents.

Methods: This new generation of quality control samples uses a bead that contains a specific amount of glucose.

EFFICACY AND SAFETY OF THE PROPOSED BIOSIMILAR AFLIBERCEPT, SDZ-AFL, IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results From the Phase 3 Mylight Study.

Purpose: The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]).

Method: Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks.

Vascular smooth muscle BK channels limit ouabain-induced vasocontraction: Dual role of the Na/K-ATPase as a hub for Src-kinase and the Na/Ca-exchanger.

Large-conductance, calcium-activated potassium channels (BK channels) and the Na/K-ATPase are expressed universally in vascular smooth muscle. The Na/K-ATPase may act via changes in the intracellular Ca concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels.

Reading skill profiles of dysfluent readers in grades 2 and 3.

Text reading fluency (TRF) is a common reading intervention target in second and third grade. TRF requires the integration of several skills that result in several pathways to dysfluent reading. However, when applying the drill-down approach to intervention targeting, practitioners are guided to consider students' rate and accuracy when reading connected text after ruling out decoding difficulties.

Pyrimidine Triones as Potential Activators of p53 Mutants.

p53 is a crucial tumor suppressor in vertebrates that is frequently mutated in human cancers. Most mutations are missense mutations that render p53 inactive in suppressing tumor initiation and progression. Developing small-molecule drugs to convert mutant p53 into an active, wild-type-like conformation is a significant focus for personalized cancer therapy.

β-TrCP-Mediated Proteolysis of Mis18β Prevents Mislocalization of CENP-A and Chromosomal Instability.

Restricting the localization of evolutionarily conserved histone H3 variant CENP-A to the centromere is essential to prevent chromosomal instability (CIN), an important hallmark of cancers. Overexpressed CENP-A mislocalizes to non-centromeric regions and contributes to CIN in yeast, flies, and human cells. Centromeric localization of CENP-A is facilitated by the interaction of Mis18β with CENP-A specific chaperone HJURP.

Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin.

Exploring the fragility of meta-analyses in ophthalmology: a systematic review.

Objective: The fragility index (FI) of a meta-analysis evaluates the extent that the statistical significance can be changed by modifying the event status of individuals from included trials. Understanding the FI improves the interpretation of the results of meta-analyses and can help to inform changes to clinical practice. This review determined the fragility of ophthalmology-related meta-analyses.