The CoREST complex inhibitor, corin, leads to decreased tumor growth, increased cellular differentiation and extended lifespan in atypical teratoid rhabdoid tumor xenograft models.

Background: Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor in infants, and more than 60% of children with ATRT die from their tumor. ATRT is associated with mutational inactivation/deletion of , a member of the SWI/SNF chromatin remodeling complex, suggesting that epigenetic events play a critical role in tumor development and progression. Moreover, disruption of SWI/SNF allows unopposed activity of epigenetic repressors, which contribute to tumorigenicity.

CoREST Complex Inhibition Alters RNA Splicing to Promote Neoantigen Expression and Enhance Tumor Immunity.

Unlabelled: Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex with RNA splicing factors and their functional consequences in tumorigenesis. Using mass spectrometry, in vivo binding assays, and cryo-EM we find that CoREST complex-splicing factor interactions are direct and perturbed by the CoREST complex inhibitor, corin, leading to extensive changes in RNA splicing in melanoma and other malignancies.

The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive sarcoma that may be seen in patients with neurofibromatosis type 1 (NF1) or occur sporadically. While surgery is the primary treatment for localized MPNST with a 61.9% overall survival rate, metastatic disease is often fatal due to resistance to systemic therapies which underscores the urgent need for effective treatments.

The perceptions of medical students of online teaching during the COVID-19 pandemic: a national survey from Jordan.

In response to the COVID-19 pandemic, Jordan declared a state of emergency on 19 March 2020, implementing a 10-week curfew and closing all educational institutions. Consequently, online learning commenced to ensure educational continuity amid the pandemic. The aim of this study was to assess medical students' perception of online teaching during this period in a limited-resource setting and to identify associated challenges.

Targeting the Epigenome Reduces Keloid Fibroblast Cell Proliferation, Migration, and Invasion.

Keloids are pathological fibroproliferative scars resulting from abnormal collagen deposition within and beyond the margins of the initial cutaneous insult. Keloids negatively impact QOL functionally and cosmetically, with current treatment modalities unsatisfactory. Recent studies indicate that epigenetic dysregulation is central to the development and progression of keloids.

p300 KAT Regulates SOX10 Stability and Function in Human Melanoma.

Unlabelled: SOX10 is a lineage-specific transcription factor critical for melanoma tumor growth; on the other hand, SOX10 loss-of-function drives the emergence of therapy-resistant, invasive melanoma phenotypes. A major challenge has been developing therapeutic strategies targeting SOX10's role in melanoma proliferation while preventing a concomitant increase in tumor cell invasion. In this study, we report that the lysine acetyltransferase (KAT) EP300 and SOX10 gene loci on chromosome 22 are frequently co-amplified in melanomas, including UV-associated and acral tumors.

Imaging features for the identification of atrial fibrillation in cryptogenic stroke patients.

Background: Whether specific imaging aspects can be used to identify cryptogenic stroke (CS) patients with high risk of underlying atrial fibrillation (AF) remains unclear. The purpose of this study was to evaluate brain-imaging features in CS patients and their utility as AF predictors.

Methods: The Nordic Atrial Fibrillation and Stroke study was a prospective observational study of CS and transient ischemic attack patients undergoing 12-month cardiac-rhythm monitoring, biomarker and clinical assessments.

p300 KAT regulates SOX10 stability and function in human melanoma.

SOX10 is a lineage-specific transcription factor critical for melanoma tumor growth, while SOX10 loss-of-function drives the emergence of therapy-resistant, invasive melanoma phenotypes. A major challenge has been developing therapeutic strategies targeting SOX10's role in melanoma proliferation, while preventing a concomitant increase in tumor cell invasion. Here, we report that the lysine acetyltransferase (KAT) and gene loci on Chromosome 22 are frequently co-amplified in melanomas, including UV-associated and acral tumors.

Smoking-Related Disease Impact in the Eastern Mediterranean Region: A Comprehensive Assessment Using Global Burden of Disease Data.

Background: Smoking remains a significant risk factor for numerous health issues, including lung cancer, chronic obstructive pulmonary disease, ischemic heart disease, stroke, and respiratory infections. This study investigates the burden of tobacco-related diseases in the Middle East and North Africa (MENA) region.

Methods: Utilizing the GBD data, we examined the risk of smoking and second-hand smoke exposure and their related causes of death and disability in the 22 MENA countries.

Vitamin D Deficiency and the Risk of Recurrent Benign Paroxysmal Positional Vertigo.

Background Benign paroxysmal positional vertigo (BPPV) is the most common cause of positional vertigo. It is a short-lived (seconds) rotatory attack of vertigo in relation to the position of the head. Vitamin D deficiency may be one of the causes leading to BPPV.

The CoREST repressor complex mediates phenotype switching and therapy resistance in melanoma.

Virtually all patients with BRAF-mutant melanoma develop resistance to MAPK inhibitors largely through nonmutational events. Although the epigenetic landscape is shown to be altered in therapy-resistant melanomas and other cancers, a specific targetable epigenetic mechanism has not been validated. Here, we evaluated the corepressor for element 1-silencing transcription factor (CoREST) epigenetic repressor complex and the recently developed bivalent inhibitor corin within the context of melanoma phenotype plasticity and therapeutic resistance.

Biological evaluation of combinations of tyrosine kinase inhibitors with Inecalcitol as novel treatments for human chronic myeloid leukemia.

Background: The use of tyrosine kinase inhibitors (TKIs) as a treatment for chronic myeloid leukemia (CML) has improved the natural history of the disease and increased the duration of survival. Tyrosine kinase inhibitors represent the success of target therapies that work on molecular targets, although some patients still have therapy failure. Vitamin D has antiproliferative, pro-apoptotic, and anti-angiogenic effects on cells, therefore it can be considered as a potential cancer preventative and treatment agent.

Update on hydroxychloroquine use in pregnancy.

It is well-known that hydroxychloroquine (HCQ) treats malaria, systemic lupus erythematosus, and rheumatoid arthritis in women for its immunomodulatory and anti-inflammatory action. Additionally, HCQ was used in cases with refractory antiphospholipid syndrome. HCQ safety was reinforced in pregnant women owing to insignificant reports of adverse pregnancy outcomes and major congenital malformation.

Direct or Indirect Surgical Approach of Zygomatic Complex Fracture: A Comparative Study.

Zygoma is considered the main support of the midface. Zygoma is frequently fractured owing to its prominent site on the face. Treatment of zygomaticomaxillary complex fractures can be performed through either conservative or surgical measures (closed or open reduction).

Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration.

Wound healing is a complex process involving phases of hemostasis, inflammation, proliferation, and remodeling. The regenerative process in the skin requires coordination between many regulators, including signaling molecules, transcription factors, and the epigenetic machinery. In this study, we show that chromatin regulators HDAC1 and LSD1, key components of the CoREST repressor complex, are upregulated in the regenerating epidermis during wound repair.

Assessment of Fraction of Exhaled Nitric Oxide and Soluble Receptor for Advanced Glycation End Products Biomarkers for Jordanian Asthmatic Children.

Purpose: Fraction of exhaled nitric oxide (FeNO) and soluble advanced glycation end-product receptor (sRAGE) are proposed as biomarkers of asthma, therefore we sought to assess their use in asthmatic children of Jordan.

Patients And Methods: We conducted a case-control study at The University of Jordan Hospital. A total of 141 asthmatic children followed by respiratory pediatricians and 118 healthy children aged 4-18 years were recruited.

Elabela is a reliable biomarker for predicting early onset preeclampsia: A comparative study.

Background: Preeclampsia (PE) is a multisystemic metabolic disease with an undetermined etiology. PE is a worldwide cause of maternal and perinatal morbidity, subdivided into early (EoPE) and late-onset (LoPE) according to 34 wk of gestation as a divider. Many researchers investigated biomarkers for predicting PE to halt its consequences on the feto-maternal outcome.

Various aspects of hearing loss in newborns: A narrative review.

Hearing loss is considered the most common birth defect. The estimated prevalence of moderate and severe hearing loss in a normal newborn is 0.1%-0.

Assessment of lipid and pigment content in suspicious melanocytic lesions to improve melanoma detection.

Melanoma is a highly aggressive form of skin cancer and the most frequent lethal malignancy diagnosed by dermatologists. Although there have been advances for predicting melanoma prognosis, there are few highly sensitive and specific diagnostic tools for clinically evaluating suspicious melanocytic lesions prior to biopsy. We have recently determined that alterations in cellular lipid and pigment content are associated with tumor progression and melanoma metastasis.

Prediction of underlying atrial fibrillation in patients with a cryptogenic stroke: results from the NOR-FIB Study.

Background: Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study.

Method: The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers.

Atrial fibrillation in cryptogenic stroke and TIA patients in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Main results.

Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians.

Patients And Methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection.

Epigenetics and cutaneous neoplasms: from mechanism to therapy.

Epigenetics encompasses heritable, reversible gene expression patterns that do not arise from mutations in genomic DNA but, rather, are regulated by DNA methylation, histone modifications, RNA modifications and ncRNAs; and epigenetic dysregulation is increasingly recognized as a mechanism of neoplastic disease progression as well as resistance to cancer therapy. This review article focuses on epigenetic modifications implicated in the progression and therapeutic resistance of common cutaneous malignancies, including basal cell carcinoma, squamous cell carcinoma, T-cell lymphoma and malignant melanoma, with an emphasis on therapeutic strategies that may be used to target such disease-associated alterations.

Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study - the importance of comprehensive clinical evaluation.

Background: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management.

Methods: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology.

Facial basal cell carcinoma: A retrospective study of 67 cases.

Background: Basal cell carcinoma (BCC) is a slow-growing malignant tumor characterized by local invasiveness but an exceptionally rare metastatic potential. It ideally affects sun-exposed skin of older patients with more propensity for the facial region.

Aim: To evaluate the different clinicopathological characteristics of the facial BCC and the efficacy and safety of diode laser for the treatment of these lesions.