Distinct Responses of Cystic Fibrosis Epithelial Cells to SARS-CoV-2 and Influenza A Virus.

The COVID-19 pandemic has underscored the impact of viral infections on individuals with cystic fibrosis (CF). Initial observations suggested lower COVID-19 rates among CF populations; however, subsequent clinical data have presented a more complex scenario. This study aimed to investigate how bronchial epithelial cells from CF and non-CF individuals, including various CF transmembrane conductance regulator (CFTR) mutations, respond to infection with SARS-CoV-2 variants and SARS-CoV.

BRAIN - Holocene archaeo-data for assessing plant-cultural diversity in Italy and other Mediterranean regions.

In the field of botany applied to archaeological and palaeoecological studies, the multi- and inter-disciplinary nature of this research produces a lack of data sharing and scattered articles in the specialty literature or in national and international journals. The vast production of archaeobotany and palynology data makes it necessary to develop a tool for the availability, accessibility, and dissemination of existing research. Many databases exist on palaeoecology, archaeobotany or pollen data.

De novo variants in DENND5B cause a neurodevelopmental disorder.

The Rab family of guanosine triphosphatases (GTPases) includes key regulators of intracellular transport and membrane trafficking targeting specific steps in exocytic, endocytic, and recycling pathways. DENND5B (Rab6-interacting Protein 1B-like protein, R6IP1B) is the longest isoform of DENND5, an evolutionarily conserved DENN domain-containing guanine nucleotide exchange factor (GEF) that is highly expressed in the brain. Through exome sequencing and international matchmaking platforms, we identified five de novo variants in DENND5B in a cohort of five unrelated individuals with neurodevelopmental phenotypes featuring cognitive impairment, dysmorphism, abnormal behavior, variable epilepsy, white matter abnormalities, and cortical gyration defects.

Clinical Consequences and Functional Impact of the Rare S737F CFTR Variant and Its Responsiveness to CFTR Modulators.

S737F is a Cystic Fibrosis (CF) transmembrane conductance regulator (CFTR) missense variant. The aim of our study was to describe the clinical features of a cohort of individuals carrying this variant. In parallel, by exploiting ex vivo functional and molecular analyses on nasal epithelia derived from a subset of S737F carriers, we evaluated its functional impact on CFTR protein as well as its responsiveness to CFTR modulators.

New pathogenic variants in ARMC5 gene in a series of Italian patients affected by primary bilateral macronodular adrenocortical hyperplasia (PBMAH).

Background: To perform genetic screening for ARMC5 gene germline pathogenic variants in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH).

Subjects And Methods: In a group of 10 PBMAH patients, we performed complete sequencing of the coding region of the ARMC5 gene and MLPA analysis for large deletion detection. In subjects with the ARMC5 variant, we searched ARMC5 gene somatic variants on tumor samples.

Supercomputing for healthtech innovation: An interview with Diem Bui, Solution Engineer at LuxProvide1.

Luxembourg's supercomputer MeluXina is open to cooperation with companies that need to process huge quantities of data. Diem Bui, Solution Engineer at LuxProvide that manages MeluXina, explains how healthtech companies can benefit from supercomputing to develop and implement innovative health technology applications.

Rescue by elexacaftor-tezacaftor-ivacaftor of the G1244E cystic fibrosis mutation's stability and gating defects are dependent on cell background.

Background: Cystic fibrosis is caused by mutations impairing expression, trafficking, stability and/or activity of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The G1244E mutation causes a severe gating defect that it is not completely rescued by ivacaftor but requires the use of a second compound (a co-potentiator). Recently, it has been proposed that the corrector elexacaftor may act also as a co-potentiator.

High prevalence of adrenal cortical adenomas in patients with cerebral meningiomas.

Purpose: Adrenal cortical adenomas (ACAs) represent one of the most common endocrine neoplasms. Recently, a genetic syndrome, characterized by tumor-suppressor ARMC5-gene mutations and causing primary macronodular bilateral adrenal hyperplasia with concomitant meningiomas of the central nervous system, has been described. Apart from this rare disorder and despite the well-known influence of steroid hormones on meningiomas, no data are available about the association between ACAs and meningiomas.

Preoperative assessment of microvessel density in nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs).

Background: Hypervascularization is a typical feature of pancreatic neuroendocrine tumors, and it frequently allows their recognition at imaging studies. However, the density of microvessels in pancreatic neuroendocrine tumors changes according to their biological behavior, and a low microvessel density is associated with higher disease aggressiveness. The primary aim was to investigate the relationship between microvessel density and aggressiveness of nonfunctioning pancreatic neuroendocrine tumors.

Pancreatic metastases after surgery for renal cell carcinoma: survival and pathways of progression.

Purpose: Metastatic ccRCC has peculiar tropism in the pancreas. We describe the characteristics and pathways of progression of patients with PM in a large multi-institutional consortium and compare them to patients with metastases from ccRCC at other sites.

Methods: Detailed clinical and histopathological data were collected.

Pancreatic resections for benign intraductal papillary mucinous neoplasms: Collateral damages from friendly fire.

Background: Surgical resection of intraductal papillary mucinous neoplasms is based on preoperative high-risk stigmata/worrisome features, but the risk of overtreatment remains high. The aim of this study was to evaluate surgical indications and perioperative and long-term complications in patients with low-grade intraductal papillary mucinous neoplasms.

Methods: Patients who underwent surgical resection between 2009 and 2018 with a final histology of low-grade intraductal papillary mucinous neoplasms were included.

The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs.

Loss-of-function mutations of the gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination.

Malignancy risk in indeterminate thyroid nodules with Hürthle cells: role of autoimmune thyroiditis.

Introduction: Hürthle cells are modified follicular thyroid cells, whose development and proliferation have been related to different stimuli inducing cellular stress. Most thyroid aspirates containing Hürthle cells are classified as indeterminate, although the specific risk of malignancy for this subtype of atypia remains unclear. The aim of our study was to assess if the presence of Hürthle cells in indeterminate thyroid nodules correlates with the risk of malignancy.

Development and initial clinical correlation of a DNA methylation-based blood test for prostate cancer.

Background: One of the principle limitations for more precise management of advanced prostate cancer is the lack of accurate biomarkers allowing estimation of tumor burden, ongoing assessment of progression, and response to treatment. Although prostate-specific antigen (PSA) performs modestly, nonsecreting cancers including those with early castrate-resistance warrant investigation of other predictive biomarkers. The objectives of these studies were to develop and perform initial validation of a circulating tumor DNA (ctDNA) methylation assay.

Positive neck margin at frozen section analysis is a significant predictor of tumour recurrence and poor survival after pancreatodudenectomy for pancreatic cancer.

Background: The possible benefit of frozen section (FS) analysis during (PD) for pancreatic ductal adenocarcinoma (PDAC) and of additional resection up to total pancreatectomy (TP) is debated. Aim of this work is to evaluate the prognostic role of positive FS analysis after PD for PDAC.

Methods: Multicentric retrospective analysis on prospective databases of three institutions.

Nerves and Pancreatic Cancer: New Insights into a Dangerous Relationship.

Perineural invasion (PNI) is defined as the presence of neoplastic cells along nerves and/or within the different layers of nervous fibers: epineural, perineural and endoneural spaces. In pancreatic cancer-particularly in pancreatic ductal adenocarcinoma (PDAC)-PNI has a prevalence between 70 and 100%, surpassing any other solid tumor. PNI has been detected in the early stages of pancreatic cancer and has been associated with pain, increased tumor recurrence and diminished overall survival.

Human liver stem cell-derived extracellular vesicles enhance cancer stem cell sensitivity to tyrosine kinase inhibitors through Akt/mTOR/PTEN combined modulation.

It is well recognized that Cancer Stem Cells (CSCs) sustain the initiation, the maintenance and the recurrence of tumors. We previously reported that extracellular vesicles (EVs) derived from human liver stem cells (HLSCs) were able to limit tumor development. In this study, we evaluated whether EV derived from HLSCs could act in synergy with tyrosine kinase inhibitors (TKIs) on apoptosis of CSCs isolated from renal carcinomas.

Growth rates and outcomes of observed large renal masses.

Introduction: The natural history of small renal masses has been well defined, leading to the recommendation of active surveillance in some patients with limited life expectancy. However, this information is less clear for large renal masses (LRM), leading to ambiguity for management in the older, comorbid patient. The objective of this study was to define the natural history, including the growth rate and metastatic risk, of LRM in order to better counsel patients regarding active surveillance.

Publish and/or perish: A urological perspective on predatory publications.

Introduction: It is an accepted axiom that academics must publish to be considered successful. Open-source journals are quickly gaining traction in the scientific community as an effective way to disseminate important research. The open-access movement includes many successful, well-respected operations, but has also spawned a plethora of journals, some predatory and others that appear to be amateurish academic traps.

Mirabegron as adjuvant treatment for patients with interstitial cystitis/bladder pain syndrome.

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) patients represent a heterogeneous group with pain and urinary storage symptoms and varying responses to current treatment options. The novel beta-3 agonist, mirabegron, has been shown to improve storage symptoms of patients with bladder overactivity; however, its effect on symptoms in the IC/BPS population has yet to be studied.

Methods: Patients diagnosed at a single IC centre with IC/BPS undergoing standard therapy were treated with additional daily mirabegron 25 mg and seen in followup post-treatment.

T1 colon cancer in the era of screening: risk factors and treatment.

Background: The aim of this study was to identify risk factors for lymph node positivity in T1 colon cancer and to carry out a surgical quality assurance audit.

Methods: The sample consisted of consecutive patients treated for early-stage colon lesions in 15 colorectal referral centres between 2011 and 2014. The study investigated 38 factors grouped into four categories: demographic information, preoperative data, indications for surgery and post-operative data.