Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome.

The spliceosome is the complex molecular machinery that sequentially assembles on eukaryotic messenger RNA precursors to remove introns (pre-mRNA splicing), a physiologically regulated process altered in numerous pathologies. We report transcriptome-wide analyses upon systematic knock down of 305 spliceosome components and regulators in human cancer cells and the reconstruction of functional splicing factor networks that govern different classes of alternative splicing decisions. The results disentangle intricate circuits of splicing factor cross-regulation, reveal that the precise architecture of late-assembling U4/U6.

Iron Metabolism in Aminolevulinic Acid-Photodynamic Therapy with Iron Chelators from the Thiosemicarbazone Group.

Iron plays a crucial role in various metabolic processes. However, the impact of 5-aminolevulinic acid (ALA) in combination with iron chelators on iron metabolism and the efficacy of ALA-photodynamic therapy (PDT) remain inadequately understood. This study aimed to examine the effect of thiosemicarbazone derivatives during ALA treatment on specific genes related to iron metabolism, with a particular emphasis on mitochondrial iron metabolism genes.

Effect of Encapsulated Phenolic Compounds of Cocoa on Growth of Lactic Acid Bacteria and Antioxidant Activity of Fortified Drinking Yogurt.

The aim of this study was to obtain drinking yogurts enriched with ACTICOA cocoa powder (ACTICOA), its extract (EACTICOA) and pure phenolics, as well as their inclusion complexes with cyclodextrins and alginate-chitosan (A-Ch) capsules, and to evaluate the effects of these additives on the viability of lactic acid bacteria (LAB) and antioxidant properties of fresh yogurts and yogurts stored for 14 days at 4 °C. The application of cocoa phenolic compounds in free form and in the form of EACTICOA to yogurts resulted in the greatest increase in the concentration of phenolic compounds and a significant improvement in the antioxidant properties of the fortified products. The highest TPC was found in yogurts enriched with free quercetin (107.

Thrombospondin-2 as a potential noninvasive biomarker of hepatocyte injury but not liver fibrosis in children with MAFLD: A preliminary study.

Aim Of The Study: Metabolic-associated fatty liver disease (MAFLD) requires close monitoring due to its increased incidence and progression to fibrosis, cirrhosis and even hepatocellular carcinoma. The search for non-invasive markers to diagnose liver fibrosis is ongoing. The aim of our study was to evaluate the serum levels of growth differentiation factor-15 (GDF-15), thrombospondin-2 (TSP2), pentraxin 3 (PTX3) and angiopoietin-like protein 8 (ANGPTL8) in children with MAFLD.

Syphilitic hepatitis.

Syphilis is a sexually transmitted multisystemic disease known as "the great imitator" due to its variable presentations. Despite being preventable and curable, it still constitutes a major health problem. Hepatic manifestation of syphilis is usually mild cholestatic liver injury but in very rare cases can become fulminant.

Surgical management of lobar cerebral cavernous malformations in children: a single-center experience.

Purpose: We aimed to determine the surgical indications and postoperative outcomes among pediatric patients with lobar cerebral cavernous malformations (CCMs).

Methods: We retrospectively reviewed pediatric patients operated on for lobar CCM between March 2010 and August 2021. Indications for surgery included (1) intracranial hemorrhage, (2) symptomatic superficially located lesion, and (3) asymptomatic CCM in non-eloquent area in case of strong parental preferences.

Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation.

Peptidyl arginine deiminases (PADIs) catalyze protein citrullination, a post-translational conversion of arginine to citrulline. The most widely expressed member of this family, PADI2, regulates cellular processes that impact several diseases. We hypothesized that we could gain new insights into PADI2 function through a systematic evolutionary and structural analysis.

Acoustic outcomes and voice-related quality of life in male-to-female transsexuals undergoing Wendler glottoplasty: a single-centre experience.

Introduction: Many transsexual women seek to feminise their voice through pitch elevation surgeries so that it becomes congruent with their gender identity. This study aims to determine the safety and effectiveness of Wendler glottoplasty (WG) in vocal feminisation through the assessment of acoustic and aerodynamic parameters of the voice, as well as voice-related quality of life (QoL) in male-to-female transsexuals.

Material And Methods: We retrospectively reviewed the medical records of transsexual women who underwent WG for voice feminisation at our institution between 2016 and 2023.

Change in the Clinical Picture of Hospitalized Patients with COVID-19 between the Early and Late Period of Dominance of the Omicron SARS-CoV-2 Variant.

This study aimed to compare the clinical picture of COVID-19 in the initial and later period of Omicron dominance and to identify populations still at risk. A retrospective comparison of the clinical data of 965 patients hospitalized during the early period of Omicron's dominance (EO, January-June 2022) with 897 patients from a later period (LO, July 2022-April 2023) from the SARSTer database was performed. Patients hospitalized during LO, compared to EO, were older, had a better clinical condition on admission, had a lower need for oxygen and mechanical ventilation, had less frequent lung involvement in imaging, and showed much faster clinical improvement.

IQGAP1 mediates the communication between the nucleus and the mitochondria via NDUFS4 alternative splicing.

Constant communication between mitochondria and nucleus ensures cellular homeostasis and adaptation to mitochondrial stress. Anterograde regulatory pathways involving a large number of nuclear-encoded proteins control mitochondrial biogenesis and functions. Such functions are deregulated in cancer cells, resulting in proliferative advantages, aggressive disease and therapeutic resistance.

Short-term exposure to ambient air pollution and COVID-19 severity during SARS-CoV-2 Delta and Omicron waves: A multicenter study.

Air pollution may affect the clinical course of respiratory diseases, including COVID-19. This study aimed to evaluate the relationship between exposure of adult patients to mean 24 h levels of particulate matter sized <10 μm (PM ) and <2.5 μm (PM ) and benzo(a)pyrene (B(a)P) during a week before their hospitalization due to SARS-CoV-2 infection and symptomatology, hyperinflammation, coagulopathy, the clinical course of disease, and outcome.

Rotational Thromboelastometry (ROTEM) in Relation to Inflammatory Biomarkers and Clinical Outcome in COVID-19 Patients.

The pathogenesis of hypercoagulability in COVID-19 patients is complex and not fully understood. Rotational thromboelastometry (ROTEM) is a viscoelastic method that allows the definition of a patient's hemostatic profile. This study aimed to assess the relationship between ROTEM parameters, the profile of inflammatory cytokines, and clinical outcomes in COVID-19 patients.

Mast Cells as a Target-A Comprehensive Review of Recent Therapeutic Approaches.

Mast cells (MCs) are the immune cells distributed throughout nearly all tissues, mainly in the skin, near blood vessels and lymph vessels, nerves, lungs, and the intestines. Although MCs are essential to the healthy immune response, their overactivity and pathological states can lead to numerous health hazards. The side effect of mast cell activity is usually caused by degranulation.

Transoral Robotic Surgery in the Management of Submandibular Gland Sialoliths: A Systematic Review.

This study aimed to systematically review the literature to determine the efficacy and safety of transoral robotic surgery (TORS) in the management of submandibular gland (SMG) sialolithiasis. PubMed, Embase, and Cochrane were searched for English-language articles evaluating TORS in the management of SMG stones published up to 12 September 2022. Nine studies with a total of 99 patients were included.

Oncolytic Adenoviruses Armed with Co-Stimulatory Molecules for Cancer Treatment.

In clinical trials, adenovirus vectors (AdVs) are commonly used platforms for human gene delivery therapy. High genome capacity and flexibility in gene organization make HAdVs suitable for cloning. Recent advancements in molecular techniques have influenced the development of genetically engineered adenovirus vectors showing therapeutic potential.

Retrospective Analysis of the Effectiveness of Remdesivir in COVID-19 Treatment during Periods Dominated by Delta and Omicron SARS-CoV-2 Variants in Clinical Settings.

Continuous evaluation of real-world treatment effectiveness of COVID-19 medicines is required due to the ongoing evolution of SARS-CoV-2 and the possible emergence of resistance. Therefore, this study aimed to analyze, in a retrospective manner, the outcomes in patients hospitalized with COVID-19 during the pandemic waves dominated by Delta and Omicron variants and treated with remdesivir (RDV) ( = 762) in comparison to a demographically and clinically matched group not treated with any antivirals ( = 1060). A logistic regression analysis revealed that RDV treatment was associated with a significantly lower risk of death during both Delta wave (OR = 0.

External validation of the Chicago Chiari Outcome Scale in adults with Chiari malformation type I.

Objective: The Chicago Chiari Outcome Scale (CCOS) serves as a standardized clinical outcome evaluation tool among patients with Chiari malformation type I (CM-I). While the reliability of this scale has been proven for pediatric patients, the literature lacks CCOS validation when used solely in adults. Therefore, this study aimed to determine the validity of the CCOS in an external cohort of adult patients.

Variability in the Clinical Course of COVID-19 in a Retrospective Analysis of a Large Real-World Database.

The COVID-19 pandemic proceeds in waves, with variable characteristics of the clinical picture resulting from the evolution of the SARS-CoV-2 virus. This study aimed to compare the epidemiological characteristics, symptomatology, and outcomes of the disease in patients hospitalized for COVID-19 during periods of different variants dominance. Comparing the periods of dominance of variants preceding the Delta variant, the Delta period was characterized by a higher share of hospitalized females, less frequent comorbidities among patients, and a different age distribution.

Differences between the course of SARS-CoV-2 infections in the periods of the Delta and Omicron variant dominance in Poland.

Introduction: Up to now, COVID‑19 caused more than 6 million deaths worldwide. So far, 5 variants of concerns have been identified, with Delta and Omicron being the subject of our analysis.

Objectives: We aimed to compare baseline characteristics and outcomes of patients hospitalized during the Delta and Omicron predominance in Poland.

Contrast-Enhanced Ultrasound in the Differentiation between the Most Common Benign Parotid Gland Tumors: A Systematic Review and Meta-Analysis.

Recently, contrast-enhanced ultrasound (CEUS) has become a promising tool in distinguishing benign from malignant parotid gland tumors. However, its usefulness in differentiating various benign parotid tumors has not been determined so far. This study aimed to systematically review the literature to determine the utility of CEUS in the preoperative differentiation between pleomorphic adenomas (PAs) and Warthin's tumors (WTs) of the parotid gland.

The Course of COVID-19 in Patients with Systemic Autoimmune Rheumatic Diseases.

Patients with systemic autoimmune rheumatic disease (SARD) have increased susceptibility to viral infections, including SARS-CoV-2. The aim of this study was to analyse the SARD patient population with COVID-19 (coronavirus disease 2019) in terms of baseline characteristics, severity, course and outcomes of the disease compared with the non-SARD group, and to identify factors associated with prognosis, including remdesivir therapy efficacy. Retrospective study comprised 8220 COVID-19 cases from the SARSTer database, including 185 with SARD.

Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects.

The removal of introns from mRNA precursors and its regulation by alternative splicing are key for eukaryotic gene expression and cellular function, as evidenced by the numerous pathologies induced or modified by splicing alterations. Major recent advances have been made in understanding the structures and functions of the splicing machinery, in the description and classification of physiological and pathological isoforms and in the development of the first therapies for genetic diseases based on modulation of splicing. Here, we review this progress and discuss important remaining challenges, including predicting splice sites from genomic sequences, understanding the variety of molecular mechanisms and logic of splicing regulation, and harnessing this knowledge for probing gene function and disease aetiology and for the design of novel therapeutic approaches.