Enhancing precision in cancer treatment: the role of gene therapy and immune modulation in oncology.

Gene therapy has long been a cornerstone in the treatment of rare diseases and genetic disorders, offering targeted solutions to conditions once considered untreatable. As the field advances, its transformative potential is now expanding into oncology, where personalized therapies address the genetic and immune-related complexities of cancer. This review highlights innovative therapeutic strategies, including gene replacement, gene silencing, oncolytic virotherapy, CAR-T cell therapy, and CRISPR-Cas9 gene editing, with a focus on their application in both hematologic malignancies and solid tumors.

Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Background: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy.

The SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) has emerged as a critical regulator in cancer biology, modulating the stability of Hypoxia-Inducible Factor 1-alpha (HIF1α) and influencing a network of hypoxia-driven pathways within the tumor microenvironment (TME). SMURF2 targets HIF1α for ubiquitination and subsequent proteasomal degradation, disrupting hypoxic responses that promote cancer cell survival, metabolic reprogramming, angiogenesis, and resistance to therapy. Beyond its role in HIF1α regulation, SMURF2 exerts extensive control over cellular processes central to tumor progression, including chromatin remodeling, DNA damage repair, ferroptosis, and cellular stress responses.

Understanding the barriers and enablers to participation in vaccine trials in a pregnant population from diverse ethnic background in an inner-city UK hospital.

Background: Vaccination during pregnancy is an important healthcare intervention for safeguarding the health of the mother and their infants. Ethnic disparities in recruitment to vaccine research studies during pregnancy potentially contribute to health inequalities. The aim of the current study was to explore the barriers and enablers influencing the willingness of pregnant women from ethnic minority backgrounds to participate in vaccine research studies.

MRSA Inhibitory Activity of Some New Pyrazolo[1,5-a]pyrimidines Linked to Arene and/or Furan or Thiophene Units.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major contributor to hospital-acquired infections and is highly resistant to treatment. Ongoing research focuses on developing new antimicrobial medications to prevent the spread of resistance. A facile method was employed to efficiently synthesize new pyrazolo[1,5-a]pyrimidines in 84-93 % yields by reacting 4-benzyl-1H-pyrazole-3,5-diamine with the respective α,β-unsaturated ketones.

Periapical surgery and different root obturation protocols for upper central incisor: A finite elements analysis.

Background: The aim of this study was to determine the effect of root canal filling using different obturation materials combined with apicoectomy in upper central incisors under loading with 1 N and 100 N. The effect of incomplete root formation was also investigated.

Methods: Based on a CBCT-scan, a model of an upper central incisor was created.

Lidocaine patch for treatment of acute localized pain in the emergency department: a systematic review and meta-analysis.

Lidocaine patches are commonly prescribed for acute localized pain. Most of the existing evidence is, however, derived from postoperative or chronic pain. The objective of this study is to assess the efficacy and safety of lidocaine patch compared to placebo patch or nonsteroidal anti-inflammatory drugs (NSAIDs) for acute localized pain.

Green, facile synthesis and evaluation of unsymmetrical carbamide derivatives as antimicrobial and anticancer agents with mechanistic insights.

A very practical method for the synthesis of unsymmetrical carbamide derivatives in good to excellent yield was presented, without the need for any catalyst and at room temperature. Using a facile and robust protocol, fifteen unsymmetrical carbamide derivatives (9-23) bearing different aliphatic amine moieties were designed and synthesized by the reaction of secondary aliphatic amines with isocyanate derivatives in the presence of acetonitrile as an appropriate solvent in good to excellent yields. Trusted instruments like IR, mass spectrometry, NMR spectra, and elemental analyses were employed to validate the purity and chemical structures of the synthesized compounds.

Estimating the prevalence of potential and actionable drug-gene interactions in Irish primary care: A cross-sectional study.

Aims: Pharmacogenetics (PGx) is increasingly recognized as a strategy for medicines optimisation and prevention of adverse drug reactions. According to guidelines produced by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG), most medicines with drug-gene interactions (DGIs) are prescribed in primary care. This study aimed to estimate the prevalence of potential and actionable DGIs involving all medicines dispensed in Irish primary care.

Interventions to improve emergency department throughput and care delivery indicators: A systematic review and meta-analysis.

Background: Emergency department (ED) crowding has repercussions on acute care, contributing to prolonged wait times, length of stay, and left without being seen (LWBS). These indicators are regarded as systemic shortcomings, reflecting a failure to provide equitable and accessible acute care. The objective was to evaluate the effectiveness of interventions aimed at improving ED care delivery indicators.

Intranodal Lymphangiography and Embolization for Management of Iatrogenic Chylous Ascites after Oncological Surgery.

Purpose: To investigate the safety and effectiveness of intranodal lymphangiography (INL) and lymphatic embolization (LE) in management of chylous ascites after oncologic surgery.

Materials And Methods: Retrospective review of records of patients who underwent INL with or without LE from January 2017 to June 2022 was performed. Adult patients with chylous ascites after oncologic surgery referred to interventional radiology after failure of conservative treatment were included.

Cell based and In vivo systematic evaluation of some Egyptian plant extracts targeting breast cancer.

Unlabelled: The prevalence of breast cancer as a significant public health concern necessitates continued exploration of natural resources for novel anti-cancer agents is crucial.

Material And Methods: Anticancer activity of plant extracts on monolayer breast cancer cell line (MCF7) with lower levels of toxicity towards normal (RPE1) underwent further assessment using a three-dimensional model (3D). The extract's effects were investigated through multiple assays including apoptosis induction using quantifying cleaved cytokeratin-18 (CK18) and DNA fragmentation.

Spectrum of Nondiabetic Kidney Diseases in Patients with Type 2 Diabetes Mellitus Who Underwent Kidney Biopsy in Egypt.

Introduction: Diabetic kidney disease (DKD) affects 30-40% of patients with diabetes. The prevalence of nondiabetic kidney disease (NDKD) in patients with type 2 diabetes mellitus (T2D) in Egypt is unknown. This study aimed to assess the prevalence of NDKD in patients with T2D in Egypt.

Efficacy of an oral lipid nanocrystal formulation of amphotericin B (MAT2203) in the neutropenic mouse model of pulmonary mucormycosis.

Invasive mucormycosis (IM) is associated with high mortality and morbidity. MAT2203 is an orally administered lipid nanocrystal formulation of amphotericin B, which has been shown to be safe and effective against other fungal infections. We sought to compare the efficacy of MAT2203 to liposomal amphotericin B (LAMB) treatment in a neutropenic mouse model of IM due to var.

Subnormal Serum Liver Enzyme Levels: A Review of Pathophysiology and Clinical Significance.

Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases can be observed in vitamin B deficiency and chronic kidney disease. Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia, Wilson's disease, deficiencies of divalent ions, or malnutrition.

Comparing Cyclic Fatigue Resistance and Free Recovery Transformation Temperature of NiTi Endodontic Single-File Systems Using a Novel Testing Setup.

The aim of this study was to assess the effect of body temperature (37 °C) on the cyclic fatigue resistance of three endodontic single-file systems using a new testing setup. One Shape new generation (OS), WaveOne™ (WO) and WaveOne GOLD (WOG), which are made from different NiTi alloys and operated in different motions (rotation/reciprocation), were evaluated. The study design included four groups.

Long-term effect of non-severe COVID-19 on pulmonary function, exercise capacities and physical activities: a cross-section study in Sakaka Aljouf.

Background: COVID-19 has serious consequences on different body systems particularly the respiratory system with its impact on pulmonary function, exercise capacities, and physical activities. This study aimed to investigate the long-term effect of COVID-19 on pulmonary function, exercise capacities, and physical activities in patients with non-severe COVID-19.

Methods: 160 individuals were selected to participate in a cross-section study.

Transforming diagnostics: The implementation of digital pathology in clinical laboratories.

Digital pathology (DP) has emerged as a cutting-edge technology that promises to revolutionise diagnostics in clinical laboratories. This perspective article explores the implementation planning and considerations of DP in a single multicentre institution in Canada, the University Health Network, discussing benefits, challenges, potential implications and considerations for future adopters. We examine the transition from traditional microscopy to digital slide scanning and its impact on pathology practice, patient care and medical research.

The effect of statins on falls and physical activity in people aged 65 and older: A systematic review.

Purpose: Statins are commonly prescribed medications with recognised side effects including muscle weakness. Despite this, little is known about their effect on the physical activity and falls risk in the older population. This paper aims to explore the relationship between statin use and the physical activity and falls risk in adults aged 65 and older.

Dataset for the cost estimation of the building envelope in the Northern Region of Morocco.

Today, in the great majority of buildings in Morocco, the exterior envelope is not insulated and is therefore not performant from a thermal point of view. This data article describes and analyses a dataset of ratios (cost by square meter that we elaborated for the estimation of the cost of buildings at an early phase of construction. The ratios also allow to take into consideration the generated cost caused by the integration of insulation materials.

Management of Teeth with Grade 3 Endo-Periodontal Lesions by Combined Endodontic and Regenerative Periodontal Therapy.

(1) Background: Severely compromised teeth affected by endo-periodontal lesions are often assigned a "hopeless" prognosis, however, there is only limited evidence available. (2) Methods: In a retrospective study, we evaluated the long-term effectiveness of combined endodontic and regenerative periodontal therapy in teeth with advanced endo-periodontal lesions: 35 patients (age 47-83 years) with a total of 39 teeth diagnosed with grade 3 endo-periodontal lesions were treated by endodontists using an operating microscope followed by regenerative periodontal surgery. (3) Results: Changes in radiographic bone levels (rBl) and probing pocket depths (PPDs) were evaluated after 1 year (T) and up to 7 years postoperatively (T).

Pigment epithelium-derived factor (PEDF) represses the glucose transporter 1 (GLUT1) mRNA expression and may be a potential therapeutic agent in psoriasis: a case-control and experimental study.

We investigated the whole blood GLUT1 mRNA expression and serum pigment epithelium-derived factor (PEDF), interleukin-6 (IL-6), fetuin-A, and pentraxin-3 (PTX3) levels in psoriatic patients and tested their correlations with the severity of psoriasis using the psoriasis area and severity index (PASI) score. Also, we tested the GLUT1 mRNA expression after an in vitro treatment of human skin fibroblast (HSF) cell lines with PEDF. The case-control part of the study recruited 74 participants (44 psoriatic patients and 30 healthy volunteers).

Efficacy of an oral lipid nanocrystal (LNC) formulation of amphotericin B (MAT2203) in the neutropenic mouse model of pulmonary mucormycosis.

Invasive mucormycosis (IM) is associated with high mortality and morbidity and commonly afflicts patients with weakened immune systems. MAT2203 is an orally administered lipid nanocrystal (LNC) formulation of amphotericin B, which has been shown to be safe and effective against other fungal infections. We sought to compare the efficacy of MAT2203 to liposomal amphotericin B (LAMB) treatment in a neutropenic mouse model of IM due to var.

Evidencing general acceptability of open-label placebo use for tackling overtreatment in primary care: a mixed methods study.

Background: Overtreatment poses a challenge to healthcare systems due to harmful consequences of avoidable side-effects and costs. This study presents the first account for examining the feasibility of placebo use for reducing overtreatment in primary care, including whether public attitudes support the use of different placebo types in place of inappropriate prescriptions of antibiotics, antidepressants, or analgesics.

Methods: We used a multi-study, mixed-methods design, including patient and public (PPI) consultations, focus groups (Study 1) and two pre-registered online experiments (Studies 2 and 3).