Exploring human pancreatic organoid modelling through single-cell RNA sequencing analysis.

Human organoids have been proposed to be powerful tools mimicking the physiopathological processes of the organs of origin. Recently, human pancreatic organoids (hPOs) have gained increasing attention due to potential theragnostic and regenerative medicine applications. However, the cellular components of hPOs have not been defined precisely.

Amyotrophic lateral sclerosis as a disease model of sarcopenia.

Sarcopenia, the progressive decline of muscle mass and function, has traditionally been viewed as an age-related process leading to a broad range of adverse outcomes. However, it has been widely reported that sarcopenia can occur earlier in life in association with various conditions (i.e.

Adherence to Mediterranean Diet and Diet Quality in Patients with Inflammatory Bowel Disease: A Single-Center, Observational, Case-Control Study.

The nutritional status in inflammatory bowel disease (IBD) is often impaired, and adherence to the Mediterranean diet (MedDiet) remains under-investigated. The aim of this study was to assess diet quality (DQ) and adherence to MedDiet in a cohort of Sardinian IBD patients. We conducted a case-control study in which 50 Crohn's disease (CD) and 50 ulcerative colitis (UC) patients were matched with 100 healthy controls each.

Cognitive Impairment in People Living with HIV and the Impact of Mood: Results from a Cross-Sectional Study.

: Human Immunodeficiency Virus (HIV) infection represents a significant public health concern and, consequently, the incidence of HIV-Associated Neurocognitive Disorder (HAND) has grown over the years. The present study aims to assess HAND with the Montreal Cognitive Assessment (MoCA) in People Living With HIV/AIDS (PLWHA) to find significant associations with cognitive impairment. : The study included 210 PLWHA, aged from 30 to 81 years, of whom, 137 (65.

Metabolic targeting of cancer associated fibroblasts overcomes T-cell exclusion and chemoresistance in soft-tissue sarcomas.

T cell-based immunotherapies have exhibited promising outcomes in tumor control; however, their efficacy is limited in immune-excluded tumors. Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the tumor microenvironment and modulating immune infiltration. Despite the identification of distinct CAF subtypes using single-cell RNA-sequencing (scRNA-seq), their functional impact on hindering T-cell infiltration remains unclear, particularly in soft-tissue sarcomas (STS) characterized by low response rates to T cell-based therapies.

A GWAS in the pandemic epicenter highlights the severe COVID-19 risk locus introgressed by Neanderthals.

Large GWAS indicated that genetic factors influence the response to SARS-CoV-2. However, sex, age, concomitant diseases, differences in ancestry, and uneven exposure to the virus impacted the interpretation of data. We aimed to perform a GWAS of COVID-19 outcome in a homogeneous population who experienced a high exposure to the virus and with a known infection status.

Unexplained hypothermia is associated with bacterial infection in the Emergency Department.

Background: Early recognition and antibiotic therapy improve the prognosis of bacterial infections. Triage temperature in the Emergency department (ED) constitutes a diagnostic and prognostic marker of infection. The objective of this study was to assess the prevalence of community-acquired bacterial infections and the diagnostic ability of conventional biological markers in patients presenting to the ED with hypothermia.

Survival as a clinical outcome and its spiritual significance in a cohort of patients with advanced central pelvic neoplastic disease undergoing total pelvic evisceration: a poorly debated issue.

Background: Patients with either treatment-resistant or relapsing advanced central pelvic neoplastic disease present with a condition responsible for debilitating symptoms and consequently poor quality of life (QoL). For these patients, therapeutic strategies are very limited and total pelvic evisceration is the only option for relieving the symptoms and increasing survival. Of note, taking charge of these patients cannot be limited to increasing their lifespan but must also be aimed at improving the clinical, psychological, and spiritual conditions.

and structural variants in atypical Hemolytic Uremic Syndrome: Prevalence, genomic characterization and impact on outcome.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disease that manifests with microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, and is associated with dysregulation of the alternative complement pathway. The chromosomal region including and is rich in repeated sequences, favoring genomic rearrangements that have been reported in several patients with aHUS. However, there are limited data on the prevalence of uncommon genomic rearrangements in aHUS and their impact on disease onset and outcomes.

circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment.

Exonic circular RNAs (circRNAs) produce predominantly non-coding RNA species that have been recently profiled in many tumors. However, their functional contribution to cancer progression is still poorly understood. Here, we identify the circRNAs expressed in soft tissue sarcoma cells and explore how the circRNAs regulate sarcoma growth in vivo.

Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity.

The standard of care is unsuccessful to treat recurrent and aggressive soft-tissue sarcomas. Interventions aimed at targeting components of the tumor microenvironment have shown promise for many solid tumors yet have been only marginally tested for sarcoma, partly because knowledge of the sarcoma microenvironment composition is limited. We employ single-cell RNA sequencing to characterize the immune composition of an undifferentiated pleiomorphic sarcoma mouse model, showing that macrophages in the sarcoma mass exhibit distinct activation states.

Mycoplasma pneumoniae Infection Associated with Anti-Factor H Autoantibodies in Atypical Hemolytic Uremic Syndrome.

Hemolytic uremic syndrome (HUS) is a rare disease characterized by hemolytic anemia, thrombocytopenia, and renal impairment mostly triggered by strains of Shiga-like toxin-producing Escherichia coli (STEC-HUS). A rarer form of HUS, defined as atypical HUS (aHUS), is associated with genetic or acquired dysregulation of the alternative pathway of the complement system and presents a poorer prognosis than STEC-HUS. Factor H autoantibodies (anti-FHs) have been reported in aHUS in 5-11% of cases and are strongly associated with the homozygous deletion of CFHR3-CFHR1 genes.

Age-related changes in the energy of human mesenchymal stem cells.

Aging is a physiological process that leads to a higher risk for the most devastating diseases. There are a number of theories of human aging proposed, and many of them are directly or indirectly linked to mitochondria. Here, we used mesenchymal stem cells (MSCs) from young and older donors to study age-related changes in mitochondrial metabolism.

and Copy Number Variations in C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis.

C3 Glomerulopathy (C3G) and Immune Complex-Mediated Membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases characterized by glomerular deposition of C3 caused by dysregulation of the alternative pathway (AP) of complement. In approximately 20% of affected patients, dysregulation is driven by pathogenic variants in the two components of the AP C3 convertase, complement C3 () and Factor B (), or in complement Factor H () and Factor I (), two genes that encode complement regulators. Copy number variations (CNVs) involving the -related genes () that give rise to hybrid FHR proteins also have been described in a few C3G patients but not in IC-MPGN patients.

Age-Related Cognitive Decline and the Olfactory Identification Deficit Are Associated to Increased Level of Depression.

Purpose: Previous studies reported a correlation between olfactory function and depression. However, in literature, no data are available for the correlation between depression and all other factors such as age, sex, olfactory, gustatory, and cognitive function in healthy subjects taken together. The aim of this study was to provide a systematic account regarding the association between those variables in a non-clinical population.

Molecular Studies and an Complement Assay on Endothelium Highlight the Genetic Complexity of Atypical Hemolytic Uremic Syndrome: The Case of a Pedigree With a Null CD46 Variant.

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease characterized by microangiopathic hemolysis, thrombocytopenia, and renal impairment and is associated with dysregulation of the alternative complement pathway on the microvascular endothelium. Outcomes have improved greatly with pharmacologic complement C5 blockade. Abnormalities in complement genes (, and ), genomic rearrangements, and anti-FH antibodies have been reported in 40-60% of cases.

Olfactory Function Is Impaired in Patients with Mastocytosis.

Background: Mastocytosis is a clinically heterogeneous disorder associated with abnormal mast cell accumulation in different organs. No data are available as regards the assessment of olfactory function and its association with mastocytosis.

Objective: The aim of the study was first to investigate odor threshold, discrimination, and identification in patients with mastocytosis compared with age-matched healthy controls (HC), and furthermore, to correlate olfactory function with the other clinical symptoms of mastocytosis.

Global study of variability in olfactory sensitivity.

Variability in human olfactory sensitivity has been attributed to individual-level factors such as genetics, age, sex, medical history of infections and trauma, neurogenerative diseases, and emotional disorders. Scarce evidence exists on the cross-cultural variation in olfactory sensitivity. Hence, we performed 2 studies to estimate the variability in olfactory threshold as a function of location and environment.

Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3.

Objective: To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA).

Methods: Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6).

Results: We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18-72).

Interpretation of the Epigenetic Signature of Facioscapulohumeral Muscular Dystrophy in Light of Genotype-Phenotype Studies.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by incomplete penetrance and intra-familial clinical variability. The disease has been associated with the genetic and epigenetic features of the D4Z4 repetitive elements at 4q35. Recently, D4Z4 hypomethylation has been proposed as a reliable marker in the FSHD diagnosis.

Effect of Olfactory and Gustatory Dysfunction and Motor Symptoms on Body Weight in Patients with Parkinson's Disease.

Background: Non-motor symptoms in Parkinson's disease (PD) are often associated with a negative impact on the patients' quality of life and on their weight regulation. The aim of this study was to assess the effect of olfactory and gustatory dysfunction, apathy, fatigue, depression, and motor symptoms on weight regulation in PD patients.

Methods: We analyzed 112 participants, 63 PD patients (mean age ± SD: 69.