Assessing variant effect predictors and disease mechanisms in intrinsically disordered proteins.

Intrinsically disordered regions (IDRs) are central to diverse cellular processes but present unique challenges for interpreting genetic variants implicated in human disease. Unlike structured protein domains, IDRs lack stable three-dimensional conformations and are often involved in regulation through transient interactions and post-translational modifications. These features can affect both the distribution of pathogenic variants and the performance of computational tools used to predict their effects.

Randomised clinical trials integrity and patient, carer and public involvement: A scoping umbrella review.

Background: Patient, carer and public involvement (PCPI), an approach being endorsed in research, may also improve research integrity. After prospective registration (https://osf.io/nfgxp), we conducted a scoping umbrella review to collate evidence on the contribution of PCPI toward the integrity of randomized clinical trials (RCTs).

Ethics and informed consent in clinical trial integrity: An international, multi-stakeholder consensus statement by Cairo Consensus Group.

Recent studies have revealed issues with ethical practice and informed consent in randomized clinical trials (RCTs). We aimed to develop an international, multi-stakeholder consensus statement on human research ethics committee approval and informed participant consent for RCTs. The consensus process encompassed a systematic scoping review, modified two-round Delphi survey, and final consensus meeting of a multi-stakeholder group, including trialists, ethics committee members, methodologists, patient representatives, journal editors, and other experts on RCTs.

A novel therapeutic prospect: a dual-acting tirzepatide for Alzheimer's disease.

Alzheimer's disease (AD), the leading cause of dementia, involves microglial activation, pro-inflammatory cytokine release, and impaired insulin signaling via insulin receptor substrate 1 (IRS-1) inhibition. Brain insulin resistance (BIR) is a key factor in AD progression, disrupting synaptic plasticity and neuronal function. Additionally, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) signaling, which regulate insulin pathways, are compromised in AD.

Buried penis; what buried the penis?

Objectives: To investigate the histological and immuno-histochemical features of dartos fascia in buried penis (BP) as compared to dartos fascia in hypospadias and normal children.

Materials And Methods: The study included 40 children, operated on in our center between January 2023 and January 2024. Patients were divided into 3 groups; : 13 patients with BP, : 14 patients with different grades of distal Hypospadias, and with 13 patients who were referred for circumcision (control group).

Berberine's paradox in Neurodegeneration: Therapeutic promise and safety challenges in Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). α-Synuclein (α-Syn) is a key protein implicated in PD pathogenesis, with its structural and biophysical properties widely investigated due to their role in disease mechanisms. The presence of Lewy bodies and Lewy neurites, pathological hallmarks of PD primarily composed of aggregated α-Syn, further underscores its critical involvement.

GABA and GABAergic dysfunction in COVID-19: Piecing the puzzle with targeting immunity and several inflammatory pathways.

Coronavirus disease 2019 (COVID-19) is a global pandemic disease caused by a new type of respiratory virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary factors contributing to inflammatory and immunological diseases in patients with severe COVID-19 are primarily attributed to the excessive activation of T cells and macrophages, resulting in the massive release of pro-inflammatory cytokines, including interleukins and chemokines. Studies have indicated that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) possesses anti-inflammatory properties in mitigating certain inflammatory disorders.

Therapy-related second malignant neoplasms on top of neuroblastoma: frequency, types and risk factors.

Objectives: The aim of the study was to evaluate the long-term effect of multi-modal, risk-based treatment protocols on the development of treatment-related secondary malignant neoplasm (SMN) in patients during or after treatment of Neuroblastoma.

Material And Methods: This retrospective study included all patients with neuroblastoma treated at Children's Cancer Hospital-Egypt from July 2007 to December 2022.

Results: 24 out of 2290 patients (1%) received risk-tailored multimodal treatment protocols suffered from either hematological (21/24) or solid (3/24) treatment-related SMN during or after treatment of their primary neuroblastoma disease.

Role of liver X receptor in multiple sclerosis: A long furtive life behind a barrier.

Liver X receptors (LXRs) are nuclear receptors that function as transcription factors regulating cholesterol metabolism and are implicated in multiple sclerosis (MS) pathogenesis. This mini-review aims to elucidate the potential role of LXRs in MS neuropathology. MS is the most prevalent inflammatory and demyelinating disease of the central nervous system (CNS), impacting both the brain and spinal cord.

Unilateral SLAM: A Simple Novel Technique to Correct Complications of Hypospadias.

Objective: To evaluate unilateral slit-like adjusted Mathieu (SLAM) as a simple and effective option for repairing hypospadias complications.

Materials And Methods: Between December 2018 and December 2023, 66 patients were treated at our center, with a minimum follow-up of 12 months. Cases included meatal retraction (n = 4), distal fistula (n = 11), and glandular dehiscence (n = 44).

The neuroprotective role of Humanin in Alzheimer's disease: The molecular effects.

Humanin (HN) is an endogenous micropeptide also known as a mitochondria-derived peptide. It has a neuroprotective effect against Alzheimer's disease (AD) and other neurodegenerative diseases by improving hippocampal acetylcholine and attenuating the development of oxidative stress and associated neurotoxicity. HN protects the neuron from the toxic effects of amyloid beta (Aβ).

15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL.

Purpose Of Review: This review provides a comprehensive understanding of the ALK gene, encompassing its prevalence, genetic alterations, and significance in neuroblastoma diagnosis, outcome prediction, and targeted therapy utilization. The insights presented aim to inform future research directions and clinical practices in this field.

Recent Findings: High risk neuroblastoma, comprising approximately 50% of all cases, presents a particularly poor prognosis.

Beyond the gut: Unraveling the multifaceted influence of microbiome on cardiovascular health.

Cardiovascular disease is one of the leading causes of death worldwide. Even while receiving adequate pharmacological treatment for their hypertension, people are nonetheless at greater risk for cardiovascular disease. There is growing evidence that the gut microbiota may have major positive and negative effects on blood pressure and illnesses related with it as more study into this topic is conducted.

Mitigating seizure-induced cognitive deficits in mice induced with pentylenetetrazol by roflumilast through targeting the NLRP3 inflammasome/BDNF/SIRT3 pathway and regulating ferroptosis.

Aims: Comorbidities with epilepsy and antiseizure medications (ASMs) are currently the main challenges in treating epilepsy. The current study evaluates for the first time the neuroprotective effect of roflumilast (ROF) alone or combined with phenytoin (PHT) against pentylenetetrazol (PTZ)-induced kindling in mice. It focuses on the crosstalk between the NOD-like receptor protein 3 (NLRP3)/caspase 1/interleukin 1β (IL-1β) cascade and the brain-derived neurotrophic factor (BDNF)/sirtuin 3 (SIRT3) pathway as possible strategies to treat epilepsy.

Evaluating the Effectiveness of Assisted Oocyte Activation in ICSI: Pairwise Meta-Analyses and Systematic Evidence Evaluation.

Background: Artificial oocyte activation (AOA) is used to improve fertilisation rates in intracytoplasmic sperm injection (ICSI) cycles.

Objectives: To assess the effectiveness of AOA on fertilisation, embryo development, and clinical outcomes, including live birth.

Search Strategy: We searched PubMed, Cochrane, and Scopus from January 1990 to March 2024 using terms related to 'artificial oocyte activation' and 'ICSI.

International multistakeholder consensus statement on post-publication integrity issues in randomized clinical trials by Cairo Consensus Group.

The number of retractions of randomized clinical trials (RCTs) following post-publication allegations of misconduct is increasing. To address this issue, we aimed to establish an international multistakeholder consensus on post-publication integrity concerns related to RCTs. After prospective registration (https://osf.

Understanding the heterogeneous performance of variant effect predictors across human protein-coding genes.

Variant effect predictors (VEPs) are computational tools developed to assess the impacts of genetic mutations, often in terms of likely pathogenicity, employing diverse algorithms and training data. Here, we investigate the performance of 35 VEPs in the discrimination between pathogenic and putatively benign missense variants across 963 human protein-coding genes. We observe considerable gene-level heterogeneity as measured by the widely used area under the receiver operating characteristic curve (AUROC) metric.

Hypospadias Reconstruction Training: Development of an Ex-Vivo Model for Objective Evaluation of Surgical Skills.

Objective: To objectively evaluate technical skill acquisition in hypospadias repair procedures during surgical training using noninvasive wearable sensor technology.

Methods: We combined subjective video evaluations with objective electromyography (EMG) measurements in a hands-on hypospadias training course. Surgeons wore wireless EMG and accelerometer sensors on their dominant hand while performing tasks on ex-vivo cadaveric calf penises.

Prognostic factors and outcome of relapsed/progressive pediatric Ewing sarcoma: single-center 10-year experience.

Background: Ewing sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Despite more intensive chemotherapy regimens and improved local control therapy, there is still a considerable rate of recurrent/progressive disease.

Methods: A retrospective study of 50 relapsed/progressive ES patients who were treated at the National Cancer Institute (NCI), Cairo University, during the period from 1st of January 2008 to the end of December 2018, to assess different prognostic variables and disease outcomes.

Bilateral adrenal neuroblastoma: peculiar pattern of a rare pediatric presentation.

Background: Bilateral suprarenal neuroblastoma (BSN) is a rare presentation. Few previously published literature showed BSN patients to have favorable pattern and prognosis. This study aim was to evaluate clinical and biological features in relation to outcome of Egyptian patients with BSN.

Apigenin ameliorates genitourinary dysfunction in a type 1 diabetic rat model via Drp1 modulation.

The present study aimed to explore the potential ameliorative effect of apigenin (APG) against diabetes-associated genitourinary complications in rats. A diabetic rat model was induced by the intraperitoneal injection of streptozotocin (STZ). All experimental animals were treated with vehicle or vehicle plus APG at a dose of 0.

Quantifying the association of sperm DNA fragmentation with assisted reproductive technology outcomes: An umbrella review.

Background: Systematic reviews and meta-analyses are instrumental in shaping clinical practice. However, their findings can sometimes be marred by discrepancies and potential biases, thereby diluting the strength of the evidence presented. Umbrella reviews serve to comprehensively assess and synthesise these reviews, offering a clearer insight into the quality of the evidence presented.