Germline BRCA pathogenic variants and hematologic adverse events in patients with ovarian carcinoma receiving PARP inhibitors: a retrospective cohort study.

Background: Patients with a germline BRCA pathogenic variant (gBRCA-PV) and advanced high grade ovarian carcinoma (aHGOC) experience higher hematologic adverse events (HAEs) when receiving platinum salts and ionizing radiations, compared to non-carriers, due to a possible higher susceptibility of the hemopoietic stem cells to DNA targeting agents. However, the incidence of PARP inhibitor (PARPi)-related HAEs according to the gBRCA-PV status is currently unknown.

Patients And Methods: We conducted a single-center retrospective cohort study to describe the occurrence of HAEs in patients with aHGOC receiving ≥8 weeks of maintenance PARPi in any line of therapy, comparing gBRCA-PVs carriers to non-carriers.

Probing hidden leptonic scalar portals using the NA64 experiment at CERN.

In this study, we demonstrate the potential of the NA64 experiment at CERN SPS to search for New Physics processes involving transitions after the collision of 100 GeV electrons with target nuclei. A new Dark Sector leptonic portal in which a scalar boson could be produced in the lepton-flavor-changing bremsstrahlung-like reaction, , is used as benchmark process. In this work, we develop a realistic Monte Carlo simulation of the NA64 experimental setup implementing the differential and total production cross-section computed at exact tree-level and applying the Weiszäcker-Williams phase space approximation.

Dark-Sector Search via Pion-Produced η and η^{'} Mesons Decaying Invisibly in the NA64h Detector.

We present the first results from a proof-of-concept search for dark sectors via invisible decays of pseudoscalar η and η^{'} mesons in the NA64h experiment at the CERN SPS. Our novel technique uses the charge-exchange reaction of 50 GeV π^{-} on nuclei of an active target as the source of neutral mesons. The η,η^{'}→invisible events would exhibit themselves via a striking signature-the complete disappearance of the incoming beam energy in the detector.

Advanced CMOS manufacturing of superconducting qubits on 300 mm wafers.

The development of superconducting qubit technology has shown great potential for the construction of practical quantum computers. As the complexity of quantum processors continues to grow, the need for stringent fabrication tolerances becomes increasingly critical. Utilizing advanced industrial fabrication processes could facilitate the necessary level of fabrication control to support the continued scaling of quantum processors.

Germline BRCA pathogenic variants in patients with ovarian cancer and post-poly (ADP-ribose) polymerase inhibitor myeloid neoplasms.

Background: Among patients with advanced high-grade ovarian carcinoma (aHGOC) treated with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis), the presence of a germline BRCA pathogenic variant (gBRCA-PV) may increase the risk of bone marrow mutagenesis resulting in postcytotoxic therapy myelodysplastic neoplasms (MDS-pCT) or acute myeloid leukemia (AML-pCT), as it is expressed in heterozygosity also by hematopoietic progenitors. We aimed to investigate the occurrence of post-PARPi MDSs/AMLs-pCTs according to gBRCA-PV status.

Patients And Methods: We conducted a retrospective single-center study to evaluate MDS/AML-pCT in patients with aHGOC and a known gBRCA-PV status receiving at least 8 weeks of maintenance PARPi, in any line of therapy, from February 2017 to December 2022.

Cardiac sympathetic neurons are additional cells affected in genetically determined arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (AC) is a familial cardiac disease, mainly caused by mutations in desmosomal genes, which accounts for most cases of stress-related arrhythmic sudden death, in young and athletes. AC hearts display fibro-fatty lesions that generate the arrhythmic substrate and cause contractile dysfunction. A correlation between physical/emotional stresses and arrhythmias supports the involvement of sympathetic neurons (SNs) in the disease, but this has not been confirmed previously.

First Results in the Search for Dark Sectors at NA64 with the CERN SPS High Energy Muon Beam.

We report the first search for dark sectors performed at the NA64 experiment employing a high energy muon beam and a missing energy-momentum technique. Muons from the M2 beamline at the CERN Super Proton Synchrotron with a momentum of 160  GeV/c are directed to an active target. The signal signature consists of a single scattered muon with momentum <80  GeV/c in the final state, accompanied by missing energy, i.

Molecular and cellular neurocardiology in heart disease.

This paper updates and builds on a previous White Paper in this journal that some of us contributed to concerning the molecular and cellular basis of cardiac neurobiology of heart disease. Here we focus on recent findings that underpin cardiac autonomic development, novel intracellular pathways and neuroplasticity. Throughout we highlight unanswered questions and areas of controversy.

Search for Light Dark Matter with NA64 at CERN.

Thermal dark matter models with particle χ masses below the electroweak scale can provide an explanation for the observed relic dark matter density. This would imply the existence of a new feeble interaction between the dark and ordinary matter. We report on a new search for the sub-GeV χ production through the interaction mediated by a new vector boson, called the dark photon A^{'}, in collisions of 100 GeV electrons with the active target of the NA64 experiment at the CERN SPS.

Sympathetic neuropathology is revealed in muscles affected by amyotrophic lateral sclerosis.

The anatomical substrate of skeletal muscle autonomic innervation has remained underappreciated since it was described many decades ago. As such, the structural and functional features of muscle sympathetic innervation are largely undetermined in both physiology and pathology, mainly due to methodological limitations in the histopathological analysis of small neuronal fibers in tissue samples. Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease which mainly targets motor neurons, and despite autonomic symptoms occurring in a significant fraction of patients, peripheral sympathetic neurons (SNs) are generally considered unaffected and, as such, poorly studied.

Constraining light thermal inelastic dark matter with NA64.

A vector portal between the Standard Model and the dark sector is a predictive and compelling framework for thermal dark matter. Through co-annihilations, models of inelastic dark matter (iDM) and inelastic Dirac dark matter (i2DM) can reproduce the observed relic density in the MeV to GeV mass range without violating cosmological limits. In these scenarios, the vector mediator behaves like a semi-visible particle, evading traditional bounds on visible or invisible resonances, and uncovering new parameter space to explain the muon anomaly.

Toll-like receptor 9 signaling after myocardial infarction: Role of p66ShcA adaptor protein.

During myocardial infarction, cellular debris is released, causing a sterile inflammation via pattern recognition receptors. These reactions amplify damage and promotes secondary heart failure. The pattern recognition receptor, Toll-like receptor 9 (TLR9) detects immunogenic fragments of endogenous DNA, inducing inflammation by NFκB.

Concomitant administration of proton pump inhibitors does not significantly affect clinical outcomes in metastatic breast cancer patients treated with ribociclib.

Background: Gastric pH changes by proton-pump-inhibitors (PPIs) were found to affect progression-free survival (PFS) in metastatic breast cancer (mBC) patients treated with palbociclib. The current study was aimed at investigating whether the same effect could occur in patients treated with ribociclib.

Patients And Methods: Patients with hormone-positive/HER-2-negative mBC candidates for first-line treatment with ribociclib were enrolled in this retrospective-cohort study.

Neurotoxic Effect of Doxorubicin Treatment on Cardiac Sympathetic Neurons.

Doxorubicin (DOXO) remains amongst the most commonly used anti-cancer agents for the treatment of solid tumors, lymphomas, and leukemias. However, its clinical use is hampered by cardiotoxicity, characterized by heart failure and arrhythmias, which may require chemotherapy interruption, with devastating consequences on patient survival and quality of life. Although the adverse cardiac effects of DOXO are consolidated, the underlying mechanisms are still incompletely understood.

COVID-19 Vaccine Effectiveness against Omicron Variant among Underage Subjects: The Veneto Region's Experience.

Even if most of the complications due to COVID-19 are observed in the elderly, in Italy the impact of COVID-19 among young people has not been negligible. Furthermore, their contribution to SARS-CoV-2 circulation is still unclear. These reasons have driven policy makers to involve subjects aged 5 to 17 years in the COVID-19 vaccination campaign.

Differences in Immunological Evasion of the Delta (B.1.617.2) and Omicron (B.1.1.529) SARS-CoV-2 Variants: A Retrospective Study on the Veneto Region's Population.

In December 2021-January 2022 the Veneto region in Italy faced an unprecedented wave of SARS-CoV-2 infections, even though both the vaccine coverage and the number of previously infected individuals keep increasing. In this study we address the protection against the SARS-CoV-2 infection offered by natural immunity and a three-dose regimen through a retrospective study based on Veneto's regional databases. In particular, we compared these protection levels during two distinct periods respectively representative of the Delta (B.

Nerve growth factor transfer from cardiomyocytes to innervating sympathetic neurons activates TrkA receptors at the neuro-cardiac junction.

Sympathetic neurons densely innervate the myocardium with non-random topology and establish structured contacts (i.e. neuro-cardiac junctions, NCJ) with cardiomyocytes, allowing synaptic intercellular communication.

Optogenetic Control of Heart Rhythm: Lightly Guiding the Cardiac Pace.

It is well appreciated that, differently from skeletal muscles, the heart contracts independently from neurogenic inputs. However, the speed and force of heartbeats are finely modulated during stresses, emotions, and daily activities, by the autonomic neurons (both parasympathetic and sympathetic) which highly innervate the myocardium. Despite this aspect of cardiac physiology has been known for long, research has only recently shed light on the biophysical mechanisms underlying the meticulous adaptation of heart activity to the needs of the organism.

Tuning the Consonance of Microscopic Neuro-Cardiac Interactions Allows the Heart Beats to Play Countless Genres.

Different from skeletal muscle, the heart autonomously generates rhythmic contraction independently from neuronal inputs. However, speed and strength of the heartbeats are continuously modulated by environmental, physical or emotional inputs, delivered by cardiac innervating sympathetic neurons, which tune cardiomyocyte (CM) function, through activation of β-adrenoceptors (β-ARs). Given the centrality of such mechanism in heart regulation, β-AR signaling has been subject of intense research, which has reconciled the molecular details of the transduction pathway and the fine architecture of cAMP signaling in subcellular nanodomains, with its final effects on CM function.

The Effectiveness of a Diverse COVID-19 Vaccine Portfolio and Its Impact on the Persistence of Positivity and Length of Hospital Stays: The Veneto Region's Experience.

The vaccination campaign for the Veneto region (northeastern Italy) started on 27 December 2020. As of early December 2021, 75.1% of the whole Veneto population has been fully vaccinated.

Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review.

Optical techniques for recording and manipulating cellular electrophysiology have advanced rapidly in just a few decades. These developments allow for the analysis of cardiac cellular dynamics at multiple scales while largely overcoming the drawbacks associated with the use of electrodes. The recent advent of optogenetics opens up new possibilities for regional and tissue-level electrophysiological control and hold promise for future novel clinical applications.