Phenotypic traits and family history in patients with 22q11.2 deletion syndrome and generalized epilepsy: A multicenter case-control study.

Objective: This study was undertaken to characterize the clinical and genetic features of patients with 22q11.2 deletion syndrome (22q11.2DS) and generalized epilepsy compared with 22q11.

Modeling Drug Responses and Evolutionary Dynamics using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple Negative Breast Cancer.

The inter- and intra-tumor heterogeneity of triple negative breast cancers (TNBC), which is reflected in diverse drug responses, interplays with tumor evolution. Here, we developed a preclinical experimental and analytical framework using treatment-naive TNBC patient-derived tumor xenografts (PDTX) to test their predictive value in personalized cancer treatment approaches. Patients and their matched PDTX exhibited concordant drug responses to neoadjuvant therapy using two trial designs and dosing schedules.

Small RNAs and tooth development: The role of microRNAs in tooth agenesis and impaction.

Background/purpose: Tooth development, or odontogenesis, is a complex process in which several molecular pathways play a key role. Recently, microRNAs, a class of approximately 20-nucleotide small RNA molecules that regulate gene expression, have been implicated in the odontogenesis process. This study aimed to assess the role of miRNAs in odontogenesis anomalies, specifically agenesis and impaction.

Exploring non-coding genetic variability in ACE2: Functional annotation and in vitro validation of regulatory variants.

The surge in human whole-genome sequencing data has facilitated the study of non-coding region variations, yet understanding their biological significance remains a challenge. We used a computational workflow to assess the regulatory potential of non-coding variants, with a particular focus on the Angiotensin Converting Enzyme 2 (ACE2) gene. This gene is crucial in physiological processes and serves as the entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 19 (COVID-19).

Cross-cultural validity and reliability of the comprehensive assessment of acceptance and commitment therapy processes (CompACT) in people with multiple sclerosis.

Purpose: The Comprehensive assessment of Acceptance and Commitment Therapy (CompACT) is a 23-item questionnaire measuring psychological flexibility, a quality of life protective factor. An 18-item version was recently produced. We assessed validity and reliability of CompACT, and equivalence of paper and electronic (eCompACT) versions in people with multiple sclerosis (PwMS) in Italy, Germany and Spain.

Online mindfulness program (COndiVIDere) for people with multiple sclerosis in the time of COVID-19: a pilot longitudinal study.

Purpose: This study aims to evaluate the feasibility and effectiveness of a mindfulness-based group intervention (The COndiVIDere program) delivered online to people with MS (PwMS) in the time of COVID-19.

Materials And Methods: This is a single-arm longitudinal study with a nested qualitative study. The COndiVIDere program is composed of five weekly sessions (1-h each) plus three booster monthly sessions.

Fatty acid binding protein 5 inhibition attenuates pronociceptive cytokine/chemokine expression and suppresses osteoarthritis pain: A comparative human and rat study.

Objective: Osteoarthritis (OA) is often accompanied by debilitating pain that is refractory to available analgesics due in part to the complexity of signaling molecules that drive OA pain and our inability to target these in parallel. Fatty acid binding protein 5 (FABP5) is a lipid chaperone that regulates inflammatory pain; however, its contribution to OA pain has not been characterized.

Design: This combined clinical and pre-clinical study utilized synovial tissues obtained from subjects with end-stage OA and rats with monoiodoacetate-induced OA.

User appraisal of a booklet for advance care planning in multiple sclerosis: a multicenter, qualitative Italian study.

Objectives: Implementation of advance care planning (ACP) in people with progressive multiple sclerosis (PwPMS) is limited. We aimed to involve users (PwPMS, significant others, and healthcare professionals involved in PwPMS care) in the evaluation and refinement of a booklet to be used during the ACP conversations.

Methods: This qualitative study consisted of cognitive interviews with PwPMS and significant others and a focus group with healthcare professionals from three Italian centers.

APOGEE 2: multi-layer machine-learning model for the interpretable prediction of mitochondrial missense variants.

Mitochondrial dysfunction has pleiotropic effects and is frequently caused by mitochondrial DNA mutations. However, factors such as significant variability in clinical manifestations make interpreting the pathogenicity of variants in the mitochondrial genome challenging. Here, we present APOGEE 2, a mitochondrially-centered ensemble method designed to improve the accuracy of pathogenicity predictions for interpreting missense mitochondrial variants.

Predictors and outcomes of pacemaker implantation in patients with cardiac amyloidosis.

Objective: We sought to investigate prevalence, incidence and prognostic implications of permanent pacemaker (PPM) implantation in patients with cardiac amyloidosis (CA), thereby identifying the predictors of time to PPM implantation.

Methods: Seven hundred eighty-seven patients with CA (602 men, median age 74 years, 571 transthyretin amyloidosis (ATTR), 216 light-chain amyloidosis (AL)) evaluated at two European referral centres were retrospectively included. Clinical, laboratory and instrumental data were analysed.

Additional lesions identified by genomic microarrays are associated with an inferior outcome in low-risk chronic lymphocytic leukaemia patients.

We explored the relevance of genomic microarrays (GM) in the refinement of prognosis in newly diagnosed low-risk chronic lymphocytic leukaemia (CLL) patients as defined by isolated del(13q) or no lesions by a standard 4 probe fluorescence in situ hybridization (FISH) analysis. Compared to FISH, additional lesions were detected by GM in 27 of the 119 patients (22.7%).

Applying multidimensional computerized adaptive testing to the MSQOL-54: a simulation study.

Background: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is one of the most commonly-used MS-specific health-related quality of life (HRQOL) measures. It is a multidimensional, MS-specific HRQOL inventory, which includes the generic SF-36 core items, supplemented with 18 MS-targeted items. Availability of an adaptive short version providing immediate item scoring may improve instrument usability and validity.

Benzodiazepine diazepam regulates cell surface β-adrenergic receptor density in human monocytes.

Downregulation of cell surface β-adrenergic receptors (β-AR) is an important adaptive response that prevents deleterious effects of receptor overstimulation. Various factors including reactive oxygen species cause β-AR downregulation. In this study, we evaluated the effects of ligands of the peripheral benzodiazepine receptor (PBR), a key protein in regulating oxidative stress, on surface density of endogenous β-and β-ARs in highly differentiated cells such as human monocytes, which express both β-AR subtypes.

Screening approaches to cardiac amyloidosis in different clinical settings: Current practice and future perspectives.

Cardiac amyloidosis is a serious and progressive infiltrative disease caused by the deposition of amyloid fibrils in the heart. In the last years, a significant increase in the diagnosis rate has been observed owing to a greater awareness of its broad clinical presentation. Cardiac amyloidosis is frequently associated to specific clinical and instrumental features, so called "red flags", and it appears to occur more commonly in particular clinical settings such as multidistrict orthopedic conditions, aortic valve stenosis, heart failure with preserved or mildly reduced ejection fraction, arrhythmias, plasma cell disorders.

Tc-99m labelled bone scintigraphy in suspected cardiac amyloidosis.

Aims: To perform evaluation of widely embraced bone scintigraphy-based non-biopsy diagnostic criteria (NBDC) for ATTR amyloid cardiomyopathy (ATTR-CM) in clinical practice, and to refine serum free light chain (sFLC) ratio cut-offs that reliably exclude monoclonal gammopathy (MG) in chronic kidney disease.

Methods And Results: A multi-national retrospective study of 3354 patients with suspected or histologically proven cardiac amyloidosis (CA) referred to specialist centres from 2015 to 2021; evaluations included radionuclide bone scintigraphy, serum and urine immunofixation, sFLC assay, eGFR measurement and echocardiography. Seventy-nine percent (1636/2080) of patients with Perugini grade 2 or 3 radionuclide scans fulfilled NBDC for ATTR-CM through absence of a serum or urine monoclonal protein on immunofixation together with a sFLC ratio falling within revised cut-offs incorporating eGFR; 403 of these patients had amyloid on biopsy, all of which were ATTR type, and their survival was comparable to non-biopsied ATTR-CM patients (p = 0.

[Ten questions about transthyretin amyloidosis].

Systemic amyloidosis is a hereditary or acquired disease characterized by deposition of amyloid insoluble fibrils into body organs and tissues, causing structural abnormalities and organ dysfunction, i.e. heart failure.

Potassium Channel KCNH1 Activating Variants Cause Altered Functional and Morphological Ciliogenesis.

The primary cilium is a non-motile sensory organelle that extends from the surface of most vertebrate cells and transduces signals regulating proliferation, differentiation, and migration. Primary cilia dysfunctions have been observed in cancer and in a group of heterogeneous disorders called ciliopathies, characterized by renal and liver cysts, skeleton and limb abnormalities, retinal degeneration, intellectual disability, ataxia, and heart disease and, recently, in autism spectrum disorder, schizophrenia, and epilepsy. The potassium voltage-gated channel subfamily H member 1 (KCNH1) gene encodes a member of the EAG (ether-à-go-go) family, which controls potassium flux regulating resting membrane potential in both excitable and non-excitable cells and is involved in intracellular signaling, cell proliferation, and tumorigenesis.

MiRLog and dbmiR: Prioritization and functional annotation tools to study human microRNA sequence variants.

The recent identification of noncoding variants with pathogenic effects suggests that these variations could underlie a significant number of undiagnosed cases. Several computational methods have been developed to predict the functional impact of noncoding variants, but they exhibit only partial concordance and are not integrated with functional annotation resources, making the interpretation of these variants still challenging. MicroRNAs (miRNAs) are small noncoding RNA molecules that act as fine regulators of gene expression and play crucial functions in several biological processes, such as cell proliferation and differentiation.

A group resilience training program for people with multiple sclerosis: Study protocol of a multi-centre cluster-randomized controlled trial (multi-READY for MS).

Introduction: REsilience and Activities for every DaY (READY) is an Acceptance and Commitment Therapy-based group resilience-training program that has preliminary empirical support in promoting quality of life and other psychosocial outcomes in people with multiple sclerosis (PwMS). Consistent with the Medical Research Council framework for developing and evaluating complex interventions, we conducted a pilot randomized controlled trial (RCT), followed by a phase III RCT. The present paper describes the phase III RCT protocol.

Cross-Country Adaptation of a Psychological Flexibility Measure: The Comprehensive Assessment of Acceptance and Commitment Therapy Processes.

Purpose: The Comprehensive assessment of Acceptance and Commitment Therapy (ACT) processes (CompACT) is a 23-item self-report questionnaire assessing psychological flexibility, which is the overarching construct underpinning the ACT framework. We conducted a two-phase project to develop validated versions of the CompACT in three languages: phase 1-cross-cultural adaptation; and phase 2-psychometric validation of the questionnaire for use in Italy, Germany and Spain. This article focuses on the first phase.

Evaluation of a program for training psychologists in an acceptance and commitment therapy resilience intervention for people with multiple sclerosis: a single-arm longitudinal design with a nested qualitative study.

Purpose: This single-arm longitudinal study evaluated the effectiveness of a program for training psychologists in delivering an acceptance and commitment therapy-based program (REsilience and Activities for every DaY; READY) for people with multiple sclerosis (PwMS).

Materials And Methods: The training encompassed three phases: (1) training workshop; (2) READY participation; (3) READY delivery to PwMS. Self-report data were collected immediately before the workshop, before and after participation in READY, and at 3- and 15-month follow-ups.

Viability of a MSQOL-54 general health-related quality of life score using bifactor model.

Background: MSQOL-54 is a multidimensional, widely-used, health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). Findings from the validation study suggested that the two MSQOL-54 composite scores are correlated. Given this correlation, it could be assumed that a unique total score of HRQOL may be calculated, with the advantage to provide key stakeholders with a single overall HRQOL score.