Dihydropyrimidine dehydrogenase polymorphisms in patients with gastrointestinal malignancies and their impact on fluoropyrimidine tolerability: Experience from a single Italian institution.

Background: Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase (DPD), encoded by the gene. About 7% of the European population is a carrier of gene polymorphisms associated with reduced DPD enzyme activity.

Aim: To assess the prevalence of polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.

Promotion of Cardiovascular Health in Africa: The Alliance for Medical Research in Africa (AMedRA) Expert Panel.

This proposed scientific statement is focused on providing new insights regarding challenges and opportunities for cardiovascular health (CVH) promotion in Africa. The statement includes an overview of the current state of CVH in Africa, with a particular interest in the cardiometabolic risk factors and their evaluation through metrics. The statement also explains the main principles of primordial prevention, its relevance in reducing noncommunicable disease and the different strategies that have been effective worldwide.

Thiol-Reactive or Redox-Active: Revising a Repurposing Screen Led to a New Invalidation Pipeline and Identified a True Noncovalent Inhibitor Against Papain-like Protease from SARS-CoV-2.

The SARS-CoV-2 papain-like protease PLpro has multiple roles in the viral replication cycle, related to both its polypeptide cleavage function and its ability to antagonize the host immune response. Targeting the PLpro function is recognized as a promising mechanism to modulate viral replication, while supporting host immune responses. However, the development of PLpro-specific inhibitors remains challenging.

Predicting Success: The Crucial Role of Preoperative Data in Refractive Surgery Outcomes.

Refractive surgery, which includes techniques such as Laser-Assisted In Situ Keratomileusis (LASIK), Photorefractive Keratectomy (PRK) and Small Incision Lenticule Extraction (SMILE), has revolutionized ophthalmology by offering advanced solutions for vision correction. However, the choice of the technique to be used in the individual patient is highly dependent on a thorough preoperative evaluation. This retrospective study aims to investigate how preoperative parameters, including corneal thickness, topography, and refraction, affect long-term post-operative clinical outcomes.

Donor-derived GD2-specific CAR T cells in relapsed or refractory neuroblastoma.

Allogeneic chimeric antigen receptor (CAR) T cells targeting disialoganglioside-GD2 (ALLO_GD2-CART01) could be a therapeutic option for patients with relapsed or refractory, high-risk neuroblastoma (r/r HR-NB) whose tumors did not respond to autologous GD2-CART01 or who have profound lymphopenia. We present a case series of five children with HR-NB refractory to more than three different lines of therapy who received ALLO_GD2-CART01 in a hospital exemption setting. Four of them had previously received allogeneic hematopoietic stem cell transplantation.

Lower Diversity of Amylase-Trypsin Inhibitors and -Released Opioid-Containing Peptides in Ancestral Compared to Modern Wheat Varieties Assessed by Proteomics and Peptidomics.

This study focused on identifying amylase-trypsin inhibitors (ATIs) in seven Norwegian-cultivated wheat varieties, including common wheat and ancestral species, and identifying potentially harmful opioid peptides within the digesta of these wheats. LC-MS/MS analysis of tryptic peptides from ATI fractions revealed that the common wheat variety Børsum exhibited the highest diversity of ATIs ( = 24), while they were less represented in tetraploid emmer ( = 11). Hexaploid wheat Bastian showed low diversity and relative abundance of ATIs.

The co-occurrence of multimorbidity and polypharmacy among middle-aged and older adults in Canada: A cross-sectional study using the Canadian Longitudinal Study on Aging (CLSA) and the Canadian Primary Care Sentinel Surveillance Network (CPCSSN).

Background: There is an increasing prevalence of multiple conditions (multimorbidity) and multiple medications (polypharmacy) across many populations. Previous literature has focused on the prevalence and impact of these health states separately, but there is a need to better understand their co-occurrence.

Methods And Findings: This study reported on multimorbidity and polypharmacy among middle-aged and older adults in two national datasets: the Canadian Longitudinal Study on Aging (CLSA) and the Canadian Primary Care Sentinel Surveillance Network (CPCSSN).

Altered microbiome and metabolome profiling in fearful companion dogs: An exploratory study.

Behavioral dysfunctions in dogs represent one of the main social concerns, since they can endanger animals and human-dog relationship. Together with the trigger stimulus (human, animal, place, scent, auditory stimuli, objects), dogs can experience stressful conditions, either in multiple settings or unique situations, more often turning into generalized fear. Such a dysfunctional behavior can be associated with genetic susceptibility, environmental factors, traumatic experiences, and medical conditions.

From tiny to immense: Geological spotlight on the Alexander Mosaic (National Archaeological Museum of Naples, Italy) using non-invasive in situ analyses.

A key challenge in the art and archaeological field is the instrumental analysis of objects and materials while preserving their integrity. In this study, the world-renowned artwork Alexander Mosaic (The Issus Battle, collection of the National Archaeological Museum of Naples, IT), the most iconic representation of the face of the Macedonian king Alexander the Great coming from a Pompeii domus, was thoroughly analyzed with mobile and non-invasive methods, within a great project of restoration started in 2020. Representative areas of the Mosaic, overall consisting of ca.

Effectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition.

Background And Aims: Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking.

Critical Issues in the Management of CRMS/CFSPID Children: A National Real-World Survey.

Background: Notwithstanding guidance from the European Cystic Fibrosis (CF) Society (ECFS) neonatal screening (NBS) working group, significant variation persists in the evaluation and management of Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) subjects, leaving many aspects of care under debate. This study reports the results of a national survey investigating management and treatment approaches of pre-school CFSPIDs in Italy.

Methods: In February 2024, a comprehensive questionnaire was distributed to all Italian CF centers.

Impact of optimal secondary cytoreductive surgery on survival outcomes in women with recurrent endometrial carcinoma: A systematic review and meta-analysis.

Background: Management of recurrent endometrial carcinoma (EC) represents a challenge. Although a complete resection of visible disease at secondary surgery (R0) is recommended, the impact of R0 on survival outcomes is unclear and pooled data are lacking.

Objective: To quantitatively assess the impact of R0 on survival outcomes in women with EC recurrence.

Unlocking the power of empagliflozin: Rescuing inflammation in hyperglycaemia- exposed human cardiomyocytes through comprehensive multi-level analysis.

Aims: Hyperglycaemic conditions increase cardiac stress, a common phenomenon associated with inflammation, aging, and metabolic imbalance. Sodium-glucose cotransporter 2 inhibitors, a class of anti-diabetic drugs, showed to improve cardiovascular functions although their mechanism of action has not yet been fully established. This study investigated the effects of empagliflozin on cardiomyocytes following high glucose exposure, specifically focusing on inflammatory and metabolic responses.

Occlusal acuity and bite force in young adults.

Occlusal tactile acuity (OTA) and bite force are essential components of the sensorimotor control of oral behaviors. While these variables have been studied independently, it has not yet been revealed whether compressive force impacts the occlusal perception mediated by the mechanoreceptive afferents in the periodontal ligament. The present study examined the effect of repetition and maximum bite force on OTA by testing nine aluminum foils of different thicknesses together with a sham test with no foil, three times each, in randomized order in 36 healthy individuals.

Altered Intracerebellar Functional Connectivity in Friedreich's Ataxia: A Graph-Theory Functional MRI Study.

Historically, Friedreich's Ataxia (FRDA) has been linked to a relatively preserved cerebellar cortex. Recent advances in neuroimaging have revealed altered cerebello-cerebral functional connectivity (FC), but the extent of intra-cerebellar FC changes and their impact on cognition remains unclear. This study investigates intra-cerebellar FC alterations and their cognitive implications in FRDA.

Obesity alters the fitness of peritumoral adipose tissue, exacerbating tumor invasiveness in renal cancer through the induction of ADAM12 and CYP1B1.

Obesity exacerbates the risk and aggressiveness of many types of cancer. Adipose tissue (AT) represents a prevalent component of the tumor microenvironment (TME) and contributes to cancer development and progression. Reciprocal communication between cancer and adipose cells leads to the generation of cancer-associated adipocytes (CAAs), which in turn foster tumor invasiveness by producing paracrine metabolites, adipocytokines, and growth factors.

EutherianCoP. An integrated biotic and climate database for conservation paleobiology based on eutherian mammals.

We present a new database, EutherianCoP, of fossil mammals which lived globally from the Late Pleistocene to the Holocene. The database includes 13,972 fossil occurrences of 786 extant or recently extinct placental mammal species, plus 155,198 current occurrences for those of them which survived to the present. The occurrences are correlated with radiometric age information.

Liver GPBAR1 Associates With Immune Dysfunction in Primary Sclerosing Cholangitis and Its Activation Attenuates Cholestasis in Abcb4-/- Mice.

Background And Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterised by progressive biliary inflammation and fibrosis, leading to liver cirrhosis and cholangiocarcinoma. GPBAR1 (TGR5) is a G protein-coupled receptor for secondary bile acids. In this study, we have examined the therapeutic potential of BAR501, a selective GPBAR1 agonist in a PSC model.

Unlocking the Potential: How Flavonoids Affect Angiogenesis, Oxidative Stress, Inflammation, Proliferation, Invasion, and Alter Receptor Interactions in Endometriosis.

Endometriosis, though not classified as a carcinogenic condition, shares features such as oxidative stress, migration, invasion, angiogenesis, and inflammation with tumor cells. This study aims to review the effects of flavonoids on these processes and their molecular mechanisms in preventing and treating endometriosis. A comprehensive review was conducted, involving a literature search in online databases using keywords like "endometriosis," "endometrioma," and "flavonoid.

Hypergammaglobulinemia in Hidradenitis Suppurativa Patients: A New Emerging Association.

Hypergammaglobulinemia is a sign of B cell and plasma cell hyperactivity marked by elevated levels of gamma globulins, proteins within the gamma fraction of serum electrophoresis, linked to diseases like acute hepatitis, Hodgkin's lymphoma, autoimmune conditions, and neoplasms. Monoclonal gammopathy of undetermined significance (MGUS) is found in 3.2% of individuals over 50 and 5.

Polystyrene nanoparticles induce DNA damage and apoptosis in HeLa cells.

Nanoplastics (NPs) are plastic particles, typically less than 100 nm in size, that result from daily life products as well as the degradation of larger plastic debris. Due to their small size and chemical composition, they can interact with biological systems in ways that larger plastic particles cannot. Humans are continuously exposed to NPs and several studies showed the potentially toxic effects of these latter on health.

Brain dynamics and personality: a preliminary study.

Personality can be considered a system characterized by complex dynamics that are extremely adaptive depending on continuous interactions with the environment and situations. The present preliminary study explores the dynamic interplay between brain flexibility and personality by taking the dynamic approach to personality into account, thereby drawing from Cloninger's psychobiological model. 46 healthy individuals were recruited, and their brain dynamics were assessed using magnetoencephalography (MEG) during the resting state.