Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: preclinical development and first-in-human intra-articular validation as therapeutics for knee osteoarthritis.

Osteoarthritis (OA) is a joint disease characterized by articular cartilage degradation. Persistent low-grade inflammation defines OA pathogenesis, with crucial involvement of pro-inflammatory M1-like macrophages. While mesenchymal stromal cells (MSC) and their small extracellular vesicles (sEV) hold promise for OA treatment, achieving consistent clinical-grade sEV products remains a significant challenge.

An assessment of burden associated with problem joints in children and adults with moderate or severe haemophilia A: analysis of the CHESS-Paediatrics and CHESS II cross-sectional studies.

Background: Clinical research has offered many definitions and fragmented perspectives of joint morbidity in haemophilia. As joint damage, pain and mobility impairment can be present without clinical record of persistent bleeding, a person-centric joint morbidity characterisation remained a priority for the haemophilia community, giving rise to the 'problem joint' concept. As diagnosing and managing joint morbidity is critical, the aim of this study was to analyse the holistic burden of problem joints in people with moderate or severe haemophilia A (HA).

Improving care experiences for premenstrual symptoms and disorders in the United Kingdom (UK): a mixed-methods approach.

Background: Poor care experiences are reported for premenstrual disorders, which may result in negative outcomes such as distress, reduced healthcare engagement, and delays to diagnosis. This research aimed to explore healthcare experiences for premenstrual symptoms in the United Kingdom and identify areas for potential improvements based on participant responses.

Method: An online survey was delivered, with participants recruited via social media.

Pipeline for development of acylated peptide based CGRP receptor antagonist with extended half-life for migraine treatment.

Migraine is a debilitating headache disorder. The disease has neurovascular origin and migraine attacks can be elicited by vasodilative neuropeptides such as alpha calcitonin gene-related peptide (αCGRP). Antagonizing CGRP actions in migraine patients has proven clinically efficient.

Preparation of anti-shrinkage branched poly (butylene succinate-co-butylene terephthalate)/cellulose nanocrystal foam with excellent degradability and thermal insulation.

Branched poly (butylene succinate-co-butylene terephthalate) (BPBST) was synthesized by in-situ polycondensation to enhance the foamability of poly (butylene succinate-co-butylene terephthalate) (PBST) and was blended with cellulose nanocrystals (CNC) to address foam shrinkage. The introduction of 2 wt% CNC increased the crystallization temperature of BPBST from 66.6 °C to 87.

MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: Targeting tumor microenvironment and PCLAF+ subtype-specific therapy.

Background: Breast cancer had been the most frequently diagnosed cancer among women, making up nearly one-third of all female cancers. Hormone receptor-positive breast cancer (HR+BC) was the most prevalent subtype of breast cancer and exhibited significant heterogeneity. Despite advancements in endocrine therapies, patients with advanced HR+BC often faced poor outcomes due to the development of resistance to treatment.

A generative framework for enhanced cell-type specificity in rationally designed mRNAs.

mRNA delivery offers new opportunities for disease treatment by directing cells to produce therapeutic proteins. However, designing highly stable mRNAs with programmable cell type-specificity remains a challenge. To address this, we measured the regulatory activity of 60,000 5' and 3' untranslated regions (UTRs) across six cell types and developed PARADE (Prediction And RAtional DEsign of mRNA UTRs), a generative AI framework to engineer untranslated RNA regions with tailored cell type-specific activity.

Emerging oral therapeutic strategies for inhibiting PCSK9.

Pharmacological inhibition of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) have been firmly established to be an effective approach to reduce low-density lipoprotein (LDL) cholesterol levels and cardiovascular events. Subcutaneous administration of monoclonal antibodies (evolocumab and alirocumab) every 2 or 4 weeks determined a 60 % reduction of LDL cholesterol levels, while the GalNac-siRNA anti PCSK9 (inclisiran) provided an effective lipid lowering activity (-50 %) after an initial subcutaneous dose, repeated after 3 months and followed by a maintenance dose every 6 months. Although these two approaches have the potentiality to bring the majority of patients at high and very-high cardiovascular risk to the appropriate LDL cholesterol targets, their cost and subcutaneous administration represent a strong limitation for their large-scale use.

Cognitive neurodynamic approaches to adaptive signal processing in wireless sensor networks.

In recent years, Wireless Sensor Networks (WSN) have become vital because of their versatility in numerous applications. Nevertheless, the attain problems like inherent noise, and limited node computation capabilities, result in reduced sensor node lifespan as well as enhanced power consumption. To tackle such problems, this study develops a Modified-Distributed Arithmetic-Offset Binary Coding-based Adaptive Finite Impulse Response (MDA-OBC based AFIR) framework.

Comparative Analysis of Preoperative Sedation Modalities: Oral Midazolam and Ketamine Versus Chloral Hydrate and Meperidine in Pediatric Tonsillectomy - A Randomized Clinical Trial.

Objective: A pre-anesthetic medication that is ideal for pediatric patients undergoing tonsillectomy should alleviate pediatric anxiety, facilitate the smooth induction of anesthesia, and have an analgesic effect for postoperative care. This study compared the effectiveness of an oral combination of midazolam and ketamine (MK) with an oral combination of chloral hydrate and meperidine (CM) as premedication in pediatric patients undergoing tonsillectomy.

Methods: This double-blind clinical trial study was conducted with 68 pediatric patients scheduled to undergo tonsillectomy.

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Integration of a specialist pharmacist-led multidisciplinary team in primary care: preventing strokes in people with atrial fibrillation across North East London.

Public Health England outlines a national ambition of anticoagulating 90% of eligible patients with atrial fibrillation (AF) by 2029. In 2019/2020, two out of three boroughs reviewed in this study were in the bottom 10% of boroughs compared with others within England. Stroke National Audit data for these three boroughs from 2019 to 2020 identified that in patients with known AF admitted to hospital with strokes, 37% were not anticoagulated.

Delayed primacy recall in AVLT is associated with medial temporal tau PET burden in cognitively unimpaired adults.

Background: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions.

From 2D kaolinite to 3D amorphous cement.

Kaolinite is a single 2D layer of kaolin or metakaolin (MK), common clays that can be characterized as layered 3D materials. We show that because of its chemical composition, kaolinite can be converted into an amorphous 3D material by chemical means. This dimensional transformation is possible due to the large surface to volume ratio and chemical reactivity of kaolinite.

Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Methods: In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries.

Second Versus First Molar Extractions in Class II Division 1 Malocclusion Treatment: A Retrospective Longitudinal Outcome Study into Maxillary Canine, Premolar, and Molar Movement.

This retrospective longitudinal outcome study comparing orthodontic extraction modalities, including extraction of maxillary first or second molars, aimed to compare the three-dimensional tooth movement of maxillary canines (C), premolars (P1, P2), and molars (M1, M2) in Class II division 1 malocclusion treatment with fixed appliances. A sample of 98 patients (mean age 13.20 ± 1.

Common Questions and Misconceptions About Energy Drinks: What Does the Scientific Evidence Really Show?

Energy drinks are a commonly consumed beverage, and studies suggest a possible performance-enhancing effect. A Google Scholar search using the keywords "energy drinks" and "exercise" yields numerous results, underscoring the voluminous research on this topic. However, there are questions regarding the effectiveness and safety of energy drinks.

Urolithin A Modulates PER2 Degradation via SIRT1 and Enhances the Amplitude of Circadian Clocks in Human Senescent Cells.

Background/objectives: Circadian clocks are endogenous systems that regulate numerous biological, physiological, and behavioral events in living organisms. Aging attenuates the precision and robustness of circadian clocks, leading to prolonged and dampened circadian gene oscillation rhythms and amplitudes. This study investigated the effects of food-derived polyphenols such as ellagic acid and its metabolites (urolithin A, B, and C) on the aging clock at the cellular level using senescent human fibroblast cells, TIG-3 cells.

Electrolytic Ni-P and Ni-P-Cu Coatings on PCM-Loaded Expanded Graphite for Enhanced Battery Thermal Management with Mechanical Properties.

This study addresses the thermal management challenge in battery systems by enhancing phase change material composites with Ni-P and Ni-P-Cu coatings on phase change material/expanded graphite structures. Traditional phase change materials are limited by low thermal conductivity and mechanical stability, which restricts their effectiveness in high-demand applications. Unlike previous studies, this work integrates Ni-P and Ni-P-Cu coatings to significantly improve both the thermal conductivity and mechanical strength of phase change material/expanded graphite composites, filling a crucial gap in battery thermal management solutions.

Evaluation of the Microstructure and Properties of As-Cast Magnesium Alloys with 9% Al and 9% Zn Additions.

The need to reduce energy consumption means that it is necessary to reduce the weight of vehicles. However, a thick wall of massive elements promotes the formation of casting defects, which must be removed by either plastic processing (straightening) or welding methods (surface and internal discontinuities). Basic alloys contain Al and Zn as the main alloying elements.

PRMT5 inhibition has a potent anti-tumor activity against adenoid cystic carcinoma of salivary glands.

Background: Adenoid cystic carcinoma (ACC) is a rare glandular malignancy, commonly originating in salivary glands of the head and neck. Given its protracted growth, ACC is usually diagnosed in advanced stage. Treatment of ACC is limited to surgery and/or adjuvant radiotherapy, which often fails to prevent disease recurrence, and no FDA-approved targeted therapies are currently available.

Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial.

Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis and stimulate liver regeneration. In a multicenter, open-label, parallel-group, phase 2 randomized controlled trial ( ISRCTN10368050 ) in n = 51 adult patients with compensated cirrhosis and Model for End-Stage Liver Disease (MELD) score ≥10 and ≤17, we evaluated the efficacy of autologous monocyte-derived macrophage therapy (n = 27) compared to standard medical care (n = 24).

The genomic architecture of circulating cytokine levels points to drug targets for immune-related diseases.

Circulating cytokines orchestrate immune reactions and are promising drug targets for immune-mediated and inflammatory diseases. Exploring the genetic architecture of circulating cytokine levels could yield key insights into causal mediators of human disease. Here, we performed genome-wide association studies (GWAS) for 40 circulating cytokines in meta-analyses of 74,783 individuals.

Efficacy and safety of non-pharmacological, pharmacological and surgical treatments for hand osteoarthritis in 2024: a systematic review.

Background: We aimed to update the 2018 systematic literature review on the efficacy and safety of treatments for hand osteoarthritis (OA), which was based on 126 studies.

Methods: We performed a systematic literature search on randomised controlled trials from June 2017 up to 31 December 2023. Risk of bias was assessed using the RoB2 tool.