Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.

Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.

Left Atrial Remodeling and Function in Various Left Ventricular Hypertrophic Phenotypes.

Aims: How the underlying etiology and pathophysiology of left ventricular (LV) hypertrophy affects LA remodeling and function remains unexplored. The present study aims to investigate the influence of various hypertrophic phenotypes on LA remodeling and function.

Methods And Results: Patients with LV hypertrophy who underwent cardiac magnetic resonance (CMR) were compared to a control group.

A Novel Staging System of Cardiac Damage in Aortic Stenosis based on Multi-Chamber Myocardial Deformation.

Aims: This study evaluates whether multi-chamber myocardial deformation analysis using speckle tracking echocardiography (STE) can enhance validated current staging systems and improve risk stratification for patients with moderate-to-severe aortic stenosis (AS).

Methods And Results: We reanalyzed 2D, Doppler, and STE data obtained from two cohorts: derivation (654 patients, median age: 82 years; 51% men) and validation (237 patients, median age: 77 years; 55% men) with at least moderate AS (aortic valve area<1.5 cm2).

Results from the international collaborative systematic literature review informing the 2023 EULAR recommendations for the treatment of systemic sclerosis.

Background: The EULAR recommendations for the treatment of systemic sclerosis (SSc) were updated in 2017, informed by a systematic literature review (SLR) completed in 2014.

Objectives: The aim of this new SLR was to provide the most up-to-date literature to underpin contemporary EULAR recommendations for the management of SSc.

Methods: 30 searches for 30 interventions (including several outcomes/clinical questions), and 1 dedicated search (with several interventions) for calcinosis were prioritised by the task force.

EULAR recommendations for the treatment of systemic sclerosis: 2023 update.

Objectives: To update the 2017 European Alliance of Associations for Rheumatology (EULAR) recommendations for treatment of systemic sclerosis (SSc), incorporating new evidence and therapies.

Methods: An international task force was convened in line with EULAR standard operating procedures. A nominal group technique exercise was performed in two rounds to define questions underpinning a subsequent systematic literature review.

CD19-CAR T-cell therapy induces deep tissue depletion of B cells.

Objectives: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo.

Methods: Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs.

First report of privet leaf blotch-associated virus (PLBaV) infecting lilac ( L.) in France.

Privet leaf blotch-associated virus (PLBaV) is an Idaeovirus discovered by high-throughput sequencing (HTS) in privet (Ligustrum japonicum L) in southern Italy in 2017 (Navarro et al., 2017). In privet, it causes a leaf blotch disease with yellowish or whitish chlorotic blotches or ringspots.

The Developmental Origin of Novel Complex Morphological Traits in Lepidoptera.

Novel traits in the order Lepidoptera include prolegs in the abdomen of larvae, scales, and eyespot and band color patterns in the wings of adults. We review recent work that investigates the developmental origin and diversification of these four traits from a gene-regulatory network (GRN) perspective. While prolegs and eyespots appear to derive from distinct ancestral GRNs co-opted to novel body regions, scales derive from in situ modifications of a sensory bristle GRN.

Improved insulin sensitivity and reproductive profile in overweight/obese PCOS patients undergoing integrative treatment with carnitines, L-arginine, L-cysteine and myo-inositol.

Objective: To evaluate the effects of a combination of carnitines, L-arginine, L-cysteine and myo-inositol on metabolic and reproductive parameters in PCOS overweight/obese patients.

Methods: This was a retrospective study analyzing information of a group of PCOS ( = 25) overweight/obesity patients, not requiring hormonal treatment, selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Modena, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of a daily oral complementary treatment with L-carnitine (500 mg), acetyl-L-carnitine (250 mg), L-arginine (500 mg), L-cysteine (100 mg) and myo-inositol (1 gr).

Validity and Reliability of Patient Activation Measure (PAM13-I) Italian Version Among Patient Undergoing Elective Surgery.

The patient activation measure (PAM), a recognized measure of how active patients are in their care, is one of the most extensively used, widely translated, and tested instruments worldwide in measuring patient activation. This study aimed to assess the psychometric properties and construct validity of the Italian version of the 13-item Patient Activation Measure (PAM13-I) among patients undergoing elective laparoscopic cholecystectomy. A multicenter study was conducted across 111 surgical units in Italy.

Net Benefit of Early Anticoagulation for Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Importance: The net clinical effect of early vs later direct oral anticoagulant (DOAC) initiation after atrial fibrillation-associated ischemic stroke is unclear.

Objective: To investigate whether early DOAC treatment is associated with a net clinical benefit (NCB).

Design, Setting, And Participants: This was a post hoc analysis of the Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation (ELAN) open-label randomized clinical trial conducted across 103 sites in 15 countries in Europe, the Middle East, and Asia between November 6, 2017, and September 12, 2022, with a 90-day follow-up.

Genomic profiling at a single center cracks the code in inborn errors of immunity.

Inborn errors of immunity (IEI) entail a diverse group of disorders resulting from hereditary or de novo mutations in single genes, leading to immune dysregulation. This study explores the clinical utility of next-generation sequencing (NGS) techniques in diagnosing monogenic immune defects. Eight patients attending the immunodeficiency clinic and with unclassified antibody deficiency were included in the analysis.

The effect of single versus group culture on cumulus-oocyte complexes from early antral follicles.

Purpose: This study aimed to evaluate the effectiveness of single versus group culture strategies for cumulus-oocyte complexes (COCs) derived from early antral follicles (EAFs), with the goal of optimizing culture conditions to increase oocyte availability for assisted reproductive technologies.

Methods: COCs isolated from EAFs (350-450 µm) from sheep ovaries were cultured in TCM199 medium supplemented with 0.15 µg/mL Zn as zinc sulfate, 10 IU/mL FSH, 10 ng/mL estradiol, 50 ng/mL testosterone, 50 ng/mL progesterone, and 5 µM Cilostamide.

Unveiling pterion variability: a meta-analytic approach to enhance neurosurgical precision.

Purpose: This meta-analytical systematic review aims at investigating the variability of the pterion, focusing on its morphological types and precise distances from various bony landmarks. Additionally, the neurosurgical significance of this critical cranial landmark is examined in depth.

Methods: The systematic review was conducted following PRISMA 2020 and Evidence-based Anatomy Workgroup guidelines for anatomical studies.

Cancer risk in carriers of TP53 germline variants grouped into different functional categories.

Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups.

[F]PSMA-1007 PET/CT-based radiomics may help enhance the interpretation of bone focal uptakes in hormone-sensitive prostate cancer patients.

Purpose: We hypothesised that applying radiomics to [F]PSMA-1007 PET/CT images could help distinguish Unspecific Bone Uptakes (UBUs) from bone metastases in prostate cancer (PCa) patients. We compared the performance of radiomic features to human visual interpretation.

Materials And Methods: We retrospectively analysed 102 hormone-sensitive PCa patients who underwent [F]PSMA-1007 PET/CT and exhibited at least one focal bone uptake with known clinical follow-up (reference standard).

Use of AI in Cardiac CT and MRI: A Scientific Statement from the ESCR, EuSoMII, NASCI, SCCT, SCMR, SIIM, and RSNA.

Artificial intelligence (AI) offers promising solutions for many steps of the cardiac imaging workflow, from patient and test selection through image acquisition, reconstruction, and interpretation, extending to prognostication and reporting. Despite the development of many cardiac imaging AI algorithms, AI tools are at various stages of development and face challenges for clinical implementation. This scientific statement, endorsed by several societies in the field, provides an overview of the current landscape and challenges of AI applications in cardiac CT and MRI.