Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Conformational Antibodies to Proteolipid Protein-1 and Its Peripheral Isoform DM20 in Patients With CNS Autoimmune Demyelinating Disorders.

Background And Objectives: Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum.

A miRNA-Based Approach in Autosomal Dominant Polycystic Kidney Disease: Challenges and Insights from Adult to Pediatric Evidence.

Autosomal dominant polycystic kidney disease (ADPKD) represents the most common inherited kidney disorder leading to kidney failure in a significant percentage of patients over time. Although previously considered as an adult disease, robust evidence demonstrated that clinical manifestations might occur during childhood and adolescence. Therefore, early identification and treatment of the disease are of cardinal importance for pediatricians to ensure the best long-term outcomes.

Dysgeusia in MASLD-related advanced chronic liver disease (ACLD): a silent driver towards the "Bermuda" triangle of malnutrition-sarcopenia-frailty severely affecting prognosis.

Background: Dysgeusia is a distortion of the sense of taste whose prevalence and relationship with nutritional status in Metabolic dysfunction-associated Steatotic Liver Disease (MASLD)-related advanced chronic liver disease (ACLD) have never been systematically explored.

Methods: 200 MASLD patients [60 ≤ F3 fibrosis, 70 compensated ACLD (cACLD), and 70 decompensated (dACLD)] were enrolled. At baseline, the Child-Pugh (CP) score was determined.

Impact of Treatment With Trifluridine/Tipiracil in Combination With Bevacizumab on Health-Related Quality of Life and Performance Status in Refractory Metastatic Colorectal Cancer: An Analysis of the Phase III SUNLIGHT Trial.

Background: The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared to FTD/TPI for treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. This analysis of SUNLIGHT investigated the impact of treatment with FTD/TPI + bevacizumab on patient quality of life (QoL) and Eastern Cooperative Oncology Group performance status (ECOG PS).

Methods: Questionnaires (EORTC QLQ-C30 and EQ-5D-5L) and ECOG PS assessments were conducted at baseline and on Day 1 of each treatment cycle.

Effect of the maternal sleep disturbances and obstructive sleep apnea on feto-placental Doppler: A systematic review.

Literature evidenced an association of maternal sleep disturbances and maternal obstructive sleep apnea with significant obstetric complications. Moreover, the maternal sleep disturbances effect on feto-placental circulation had not been extensively examined. Our objective is to explore the possible maternal sleep disturbances impact on the feto-placental indices evaluated through the Doppler study.

Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.

We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants.

Pulmonary Arterial Hypertension Incidence in Scleroderma Patients Treated with Bosentan for Digital Ulcers: Evidence from the Italian SPRING Registry.

Objective: Bosentan (BOS) is approved for treating pulmonary arterial hypertension (PAH) and preventing digital ulcers (DU) in systemic sclerosis (SSc). Our study aimed to evaluate whether BOS prescribed for DU could reduce the incidence of PAH in a large SSc cohort from the SPRING registry.

Methods: Patients with SSc from the SPRING registry, meeting ACR/EULAR 2013 classification criteria with data on PAH onset, DU status, BOS exposure, and at least a one-year follow-up between 2015 and 2020, and no known PAH at baseline were included.

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.

High-resolution isotopic data link settlement complexification to infant diets within the Roman Empire.

Our study explores the potential relationship between infant feeding practices and settlement complexity in the Roman Empire through high-resolution Bayesian-modeled stable isotope measurements from incremental dentine. We compiled isotopic data from permanent first molars of individuals from various Roman sites: five from Bainesse (UK), 30 from Thessaloniki (Greece), along with new carbon and nitrogen isotope analyses from four individuals from Pompeii and six from Ostia Via del Mare (AVM). Our results reveal significant inter-site variability in breastfeeding durations, ranging from 1.

The current clinical approach to feeding and eating disorders aimed to increase personalization of management.

Feeding and eating disorders (FEDs) are a heterogeneous grouping of disorders at the mind-body interface, with typical onset from childhood into emerging adulthood. They occur along a spectrum of disordered eating and compensatory weight management behaviors, and from low to high body weight. Psychiatric comorbidities are the norm.

Biologics and small molecules: the re-evolution in the treatment of atopic dermatitis in children and adolescents. Current state of the art and future perspectives.

Introduction: In recent years, the understanding of atopic dermatitis (AD) pathogenetic mechanisms has expanded and now it is recognized that Th2 immune axis dysregulation is pivotal to AD pathogenesis. The advent of biological drugs and small molecules have marked a revolution in the treatment of AD. Dupilumab, targeting IL-4 and IL-13, has been the first to demonstrate efficacy in treating moderate to severe AD by modulating type-2 inflammation pathways.

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.

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.

Avenanthramide A potentiates Bim-mediated antineoplastic properties of 5-fluorouracil targeting KDM4C//GSK-3 negative feedback loop in colorectal cancer.

Chemoresistance to 5-fluorouracil (5-FU) is a significant challenge in treating colorectal cancer (CRC). Novel combined regimens to thwart chemoresistance are therefore urgently needed. Herein, we demonstrated that the combination of Avenanthramide A (AVN A) and 5-FU has significant therapeutic advantages against CRC.

Epidemiology, management and patient needs in myasthenia gravis: an Italian multistakeholder consensus based on Delphi methodology.

Objectives: To provide comprehensive information on the burden of myasthenia gravis (MG) in Italy, including the unmet needs of patients and several other aspects related to the disease, based on skilled viewpoints of MG experts.

Design: Iterative analysis conducted in accordance with the best practices of the Delphi method, including anonymity, controlled feedback, and statistical stability of consensus.

Setting And Participants: 24 clinicians, 18 public health experts and 4 patient associations experts completed all the Delphi iterations between 18 April and 3 July 2023, for a total of 46 participants from several Italian Regions.

Deficits in reaching movements under visual interference as a novel diagnostic marker for mild cognitive impairment.

Patients with Mild Cognitive Impairment (MCI) may exhibit poorer performance in visuomotor tasks than healthy individuals, particularly under conditions with high cognitive load. Few studies have examined reaching movements in MCI and did so without assessing susceptibility to distractor interference. This proof-of-concept study analyzed the kinematics of visually guided reaching movements towards a target dot placed along the participants' midsagittal/reaching axis.

Identifying Cladribine prescription pattern in MS: an Italian multicentre study.

Background: Characterizing Cladribine tablets prescription pattern in daily clinical practice is crucial for optimizing multiple sclerosis (MS) treatment.

Objectives: To describe efficacy, safety profile and new disease-modifying therapy (DMT) prescriptions following Cladribine treatment.

Design: Independent retrospective cohort study in patients followed at six Italian MS centres.

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.

Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma.

Purpose: Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.

Experimental Design: In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate the association between sustained objective responses and transcriptional profiles, immune cell dynamics in tumor tissue and peripheral blood samples, as well as circulating cytokine levels.

The North American Repository for Archaeological Isotopes.

Here, we present the North American Repository for Archaeological Isotopes (NARIA), the largest open-access compilation of previously reported isotopic measurements (n = 28,374) from bioarchaeological samples in North America (i.e., Canada, Greenland, Mexico, and the United States of America) covering a time-frame of more than 12,000 years.