A dormant overmassive black hole in the early Universe.

Recent observations have found a large number of supermassive black holes already in place in the first few hundred million years after the Big Bang, many of which seem to be overmassive relative to their host galaxy stellar mass when compared with local relation. Several different models have been proposed to explain these findings, ranging from heavy seeds to light seeds experiencing bursts of high accretion rate. Yet, current datasets are unable to differentiate between these various scenarios.

Evidence-Based Data on the Diagnostic Role and Clinical Usefulness of [F]FDG PET/CT in Endocarditis and Cardiac Device Infections.

Infective endocarditis and infection of cardiac devices are conditions characterized by high morbidity and mortality, thus requiring a prompt diagnosis. Advanced imaging modalities are often required in the management of infectious endocarditis according to guidelines. The aim of this review is to collect and describe evidence-based knowledge about the diagnostic role and clinical usefulness of [F]FDG PET/CT in endocarditis and cardiac device infections based on published systematic reviews and meta-analyses on this topic and on recent guidelines.

Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients.

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients.

Blood pressure, brain lesions and cognitive decline in patients with atrial fibrillation.

Background: The influence of atrial fibrillation (AF) and blood pressure (BP) on brain lesions and cognitive function is unclear. We aimed to investigate the association of BP with different types of brain lesions and cognitive decline in patients with AF.

Methods: Overall, 1,213 AF patients underwent standardized brain magnetic resonance imaging at baseline and after 2 years, as well as yearly neurocognitive testing.

Time-resolved cryogenic electron tomography for the study of transient cellular processes.

Cryogenic electron tomography (cryo-ET) is the highest resolution imaging technique applicable to the life sciences, enabling subnanometer visualization of specimens preserved in their near native states. The rapid plunge freezing process used to prepare samples lends itself to time-resolved studies, which researchers have pursued for in vitro samples for decades. Here, we focus on developing a freezing apparatus for time-resolved studies in situ.

A recently quenched galaxy 700 million years after the Big Bang.

Local and low-redshift (z < 3) galaxies are known to broadly follow a bimodal distribution: actively star-forming galaxies with relatively stable star-formation rates and passive systems. These two populations are connected by galaxies in relatively slow transition. By contrast, theory predicts that star formation was stochastic at early cosmic times and in low-mass systems.

Assessment of post-thrombectomy brain hemorrhage in acute ischemic stroke with dual-energy CT: how reliable is it in clinical practice?

Purpose: Acute ischemic stroke is currently among the main causes of mortality in Western countries. The current guidelines suggest different flowcharts of diagnostic work-up and treatment modalities, including endovascular thrombectomy. Immediately after intra-arterial recanalization, a brain CT scan is usually performed to assess for the presence of peri-procedural complications; in this setting, it is very hard, if possible, to differentiate blood from iodinated contrast material, which is normally present in ischemic tissue because of BBB disruption.

Patients on vitamin K treatment: is switching to direct-acting oral anticoagulation cost-effective? A target trial on a prospective cohort.

Aims: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment.

PEALut in the Dietary Management of Patients with Acute Ischemic Stroke: A Prospective Randomized Controlled Clinical Trial.

Acute ischemic stroke (AIS), which represents 87% of all strokes, is caused by reduced blood supply to the brain associated with a prolonged inflammatory process that exacerbates brain damage. The composite containing co-ultramicronized Palmitoylethanolamide and luteolin (PEALut) is known to promote the resolution of neuroinflammation, being a promising nutritional approach to contrast inflammatory processes occurring in AIS. This study included 60 patients affected by acute ischemic stroke and undergoing thrombolysis.

A small and vigorous black hole in the early Universe.

Several theories have been proposed to describe the formation of black hole seeds in the early Universe and to explain the emergence of very massive black holes observed in the first thousand million years after the Big Bang. Models consider different seeding and accretion scenarios, which require the detection and characterization of black holes in the first few hundred million years after the Big Bang to be validated. Here we present an extensive analysis of the JWST-NIRSpec spectrum of GN-z11, an exceptionally luminous galaxy at z = 10.

A Gad2 specific Slc6a8 deletion recapitulates the contextual and cued freezing deficits seen in Slc6a8 mice.

The creatine (Cr)-phosphocreatine shuttle is essential for ATP homeostasis. In humans, the absence of brain Cr causes significant intellectual disability, epilepsy, and language delay. Mutations of the creatine transporter (SLC6A8) are the most common cause of Cr deficiency.

Safety of Subcutaneous Daratumumab in Anti-CD38 Monoclonal Antibody-Naïve Patients with Plasma Cell Disorders: A Multicenter Real-Life Experience.

Background: Daratumumab, an anti-CD38 monoclonal antibody, is used for treatment of multiple myeloma (MM) and light chain amyloidosis at an intravenous dosage of 16 mg/kg or at a subcutaneous fixed dose of 1800 mg. However, the subcutaneous formulation has only recently been approved in Europe, and real-life data on its safety are still few.

Objective: In this multicenter retrospective real-life experience, we provided evidence for the safety of subcutaneous daratumumab in plasma cell disorders.

Mid-term changes in cognitive functions in patients with atrial fibrillation: a longitudinal analysis of the Swiss-AF cohort.

Background: Longitudinal association studies of atrial fibrillation (AF) and cognitive functions have shown an unclear role of AF-type and often differ in methodological aspects. We therefore aim to investigate longitudinal changes in cognitive functions in association with AF-type (non-paroxysmal vs. paroxysmal) and comorbidities in the Swiss-AF cohort.

Carbonaceous dust grains seen in the first billion years of cosmic time.

Large dust reservoirs (up to approximately 10M) have been detected in galaxies out to redshift z ≃ 8, when the age of the Universe was only about 600 Myr. Generating substantial amounts of dust within such a short timescale has proven challenging for theories of dust formation and has prompted the revision of the modelling of potential sites of dust production, such as the atmospheres of asymptotic giant branch stars in low-metallicity environments, supernova ejecta and the accelerated growth of grains in the interstellar medium. However, degeneracies between different evolutionary pathways remain when the total dust mass of galaxies is the only available observable.

Immunogenicity after two and three doses of mRNA vaccine in patients with cancer treated with exclusive radiotherapy.

Background And Purpose: Data on immunoresponse after SARS-CoV-2 vaccines for patients treated with exclusive radiotherapy (RT) are scarce. Since RT may affect the immune system, we conducted the MORA trial (Antibody response and cell-mediated immunity of MOderna mRNA-1273 vaccine in patients treated with RAdiotherapy).

Materials And Methods: Data regarding humoral and cellular immune response of patients treated with RT were prospectively collected after the second and third dose of mRNA vaccines.

Assessing the risk of oil spill impacts and potential biodiversity loss for coastal marine environment at the turn of the COVID-19 pandemic event.

The Tuscan Archipelago, with its great environmental and economic importance, is one of the highest oil spill density areas in the Western Mediterranean. In this study, an interdisciplinary approach, based on numerical applications and experimental methods, was implemented to quantify the risk of oil spill impact along the rocky shores of this archipelago in relation to the maritime activities. The risk, defined as a combination of the hazard and the damage, was quantified for the biennial 2019-2020 in order to account for the effects generated by the COVID-19 pandemic restrictions on the local maritime traffic.

A predictive model of polymetastatic disease from a multicenter large retrospectIve database on colorectal lung metastases treated with stereotactic ablative radiotherapy: The RED LaIT-SABR study.

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD.

Bone Morphogenetic Protein 10-A Novel Biomarker to Predict Adverse Outcomes in Patients With Atrial Fibrillation.

Background Patients with atrial fibrillation (AF) face an increased risk of death and major adverse cardiovascular events (MACE). We aimed to assess the predictive value of the novel atrial-specific biomarker BMP10 (bone morphogenetic protein 10) for death and MACE in patients with AF in comparison with NT-proBNP (N-terminal prohormone of B-type natriuretic peptide). Methods and Results BMP10 and NT-proBNP were measured in patients with AF enrolled in Swiss-AF (Swiss Atrial Fibrillation Study), a prospective multicenter cohort study.

Saturated Fatty Acid Chain Length and Risk of Cardiovascular Disease: A Systematic Review.

The purpose of this systematic review was to evaluate the impact of saturated fatty acid chain lengths on the development of cardiovascular disease (CVD). The importance of replacement macronutrients is also discussed. PubMed, CINAHL, and Cochrane library were searched for relevant prospective cohort studies that measured SFA chain length via diet analysis through October of 2020.

Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation.

Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID.

Selection Criteria and Treatment Outcome for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Unfit for Platinum-Based First-Line Therapy: Results of the MOON-OSS Observational Trial.

Limited evidence is available concerning the selection criteria and the outcomes of platinum unfit newly diagnosed advanced NSCLC patients receiving single-agent chemotherapy. We retrospectively collected data on consecutive, stage IIIB-IV, EGFR/ALK negative and PD-L1 < 50% NSCLC patients treated with first-line single agent chemotherapy. Baseline characteristics, outcome measures and toxicities were recorded, as well as criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy.

Efficacy and safety of belantamab-mafodotin in triple-refractory multiple myeloma patients: A multicentric real-life experience.

Belantamab-mafodotin is an innovative and selective treatment for multi-refractory/relapsed multiple myeloma (MM) patients; however, available real-life experiences on efficacy and safety are limited. In this real-world multicentric retrospective study, we enrolled 28 MM patients treated in four Hematology units of Campania region, Italy, who received a median of six treatment lines prior to belantamab-mafodotin. The overall response rate (ORR) was 40% (complete remission, CR, 11%; very good partial remission, VGPR, 11%; and partial remission, PR, 18%), with a median progression-free survival (PFS) and overall survival (OS) of 3 and 8 months, respectively.

Prevalence and risk of inappropriate dosing of direct oral anticoagulants in two Swiss atrial fibrillation registries.

Background: Direct oral anticoagulants (DOACs) have a favourable risk-benefit profile compared to vitamin K-antagonists (VKAs) in atrial fibrillation (AF). Dosing is based on age, weight and renal function, without need of routine monitoring.

Methods And Results: In two prospective, multicentre AF cohorts (Swiss-AF, BEAT-AF) patients were stratified as receiving VKAs or adequately-, under- or overdosed DOACs, according to label.