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What are the molecular determinants of protein–protein binding affinity and whether they are similar to those regulating fold stability are two major questions of molecular biology, whose answers bring important implications both from a theoretical and applicative point of view. Here, we analyze chemical and physical features on a large dataset of protein–protein complexes with reliable experimental binding affinity data and compare them with a set of monomeric proteins for which melting temperature data was available. In particular, we probed the spatial organization of protein (1) intramolecular and intermolecular interaction energies among residues, (2) amino acidic composition, and (3) their hydropathy features. Analyzing the interaction energies, we found that strong Coulombic interactions are preferentially associated with a high protein thermal stability, while strong intermolecular van der Waals energies correlate with stronger protein–protein binding affinity. Statistical analysis of amino acids abundances, exposed to the molecular surface and/or in interaction with the molecular partner, confirmed that hydrophobic residues present on the protein surfaces are preferentially located in the binding regions, while charged residues behave oppositely. Leveraging on the important role of van der Waals interface interactions in binding affinity, we focused on the molecular surfaces in the binding regions and evaluated their shape complementarity, decomposing the molecular patches in the 2D Zernike basis. For the first time, we quantified the correlation between local shape complementarity and binding affinity via the Zernike formalism. In addition, considering the solvent interactions via the residue hydropathy, we found that the hydrophobicity of the binding regions dictates their shape complementary as much as the correlation between van der Waals energy and binding affinity. In turn, these relationships pave the way to the fast and accurate prediction and design of optimal binding regions as the 2D Zernike formalism allows a rapid and superposition-free comparison between possible binding surfaces.

Although definitions of emotion dysregulation infer difficulties in selecting and implementing emotion regulation (ER) strategies, surprisingly few studies have examined the relationship between trait emotion dysregulation and a wide range of specific ER strategies. The present study used a data-driven approach to assess trait- and state-related ER strategy use in 99 women (aged 18–55) recruited from the community with varying levels of trait emotion dysregulation. Participants completed self-report questionnaires assessing habitual ER strategy implementation and self-ratings of ER strategy use in vivo during negative mood inductions. Principal components analysis revealed four self-report questionnaire-based and three mood-induction-based groupings comprising both optimal and suboptimal strategies. After adjusting for demographic and clinical variables, results from self-report questionnaires indicated that trait emotion dysregulation was significantly associated with higher endorsements of suboptimal strategies in two groupings (e.g., self-criticism, rumination, and social withdrawal; catastrophizing and blaming others) and lower endorsements of optimal ER strategies in one grouping (e.g., cognitive reappraisal and problem solving). In the context of mood induction, trait emotion dysregulation was significantly associated with higher endorsements of suboptimal ER strategies from one cluster only (e.g., expressive suppression, thought avoidance, and self-criticism). Such transdiagnostic, data-driven approaches can uncover how the application of specific ER strategies both habitually and during negative mood states is associated with trait emotion dysregulation.

In this paper, we compare the distribution of Elsevier Scopus subject areas of authors’ documents, their bibliographical references and their citing documents. We compute the complement of the Herfindahl–Hirschman index as a measure of multidisciplinarity. We analyse a sample of 120 researchers belonging to two groups, one from the Italian Institute of Technology (IIT, whose work is expected to be highly multidisciplinary) and one from the National Institute for Nuclear Physics (INFN, whose work is expected to be much less multidisciplinary). We show that the two groups are distinguishable through the measured index values. By using the subject areas of authors’ bibliographical references we obtain a better identification of the two groups than relying on the subject areas of the author’s documents. We then extend the analysis to 3317 researchers belonging to seven Italian Scientific-Disciplinary sectors (SSD) providing insights about the degree of multidisciplinarity within each SSD. The results seem interesting for assessing the multidisciplinarity of younger researchers with scarce scientific output and few citations.

Heart failure is associated with a range of comorbidities that have the potential to impair both quality of life and clinical outcome. Unfortunately, noncardiac diseases are underrepresented in large randomized clinical trials, and their management remains poorly understood. In clinical practice, the prevalence of comorbidities in heart failure is high. Although the prognostic impact of comorbidities is well known, their prevalence and impact in specific heart failure settings have been overlooked. Many studies have described specific single noncardiac conditions, but few have examined their overall burden and grading in patients with multiple comorbidities. The risk of comorbidities in patients with heart failure rises with more advanced disease, older age, and increased frailty-three conditions that are poorly represented in clinical trials. The pathogenic links between comorbidities and heart failure involve many pathways and include neurohormonal overdrive, inflammatory activation, oxidative stress, and endothelial dysfunction. Such interactions may worsen prognoses, but details of these relationships are still under investigation. We propose a shift from cardiac-focused care to a more systemic approach that considers all noncardiac diseases and related medications. Some new drugs class such as ARNI or SGLT2 inhibitors could change prognosis by acting directly or indirectly on metabolic disorders and related vascular consequences.

Background:\ud The inverse relationship between body mass index (BMI) and natriuretic peptide levels complicates the diagnosis of heart failure (HF) in obese patients. Assessment of congestion with ultrasound could facilitate HF diagnosis but it is unclear if any relationship exists amongst BMI, inferior vena cava (IVC) diameter and the number of B-lines.\ud \ud Methods:\ud We performed a comprehensive echocardiographic evaluation within 24 h from hospital admission in patients with HF, including lung B-lines and IVC diameter, and studied their relationship with BMI and outcome.\ud \ud Results:\ud 216 patients (median age 81 (77–86) years) were enrolled. Median number of B-lines was 31 (IQR 26–38), median IVC diameter was 23 (22–25) mm and median BNP 991 (727–1601) pg/mL. BMI was inversely correlated with B-lines (r = − 0.50, p

Although the Mediterranean Sea covers approximately a 0.7% of the world’s ocean area, it represents a major reservoir of marine and coastal biodiversity. Among marine organisms, sponges (Porifera) are a key component of the deep-sea benthos, widely recognized as the dominant taxon in terms of species richness, spatial coverage, and biomass. Sponges are evolutionarily ancient, sessile filter-feeders that harbor a largely diverse microbial community within their internal mesohyl matrix. In the present work, we firstly aimed at exploring the biodiversity of marine sponges from four different areas of the Mediterranean: Faro Lake in Sicily and “Porto Paone”, “Secca delle fumose”, “Punta San Pancrazio” in the Gulf of Naples. Eight sponge species were collected from these sites and identified by morphological analysis and amplification of several conserved molecular markers (18S and 28S RNA ribosomal genes, mitochondrial cytochrome oxidase subunit 1 and internal transcribed spacer). In order to analyze the bacterial diversity of symbiotic communities among these different sampling sites, we also performed a metataxonomic analysis through an Illumina MiSeq platform, identifying more than 1500 bacterial taxa. Amplicon Sequence Variants (ASVs) analysis revealed a great variability of the host-specific microbial communities. Our data highlight the occurrence of dominant and locally enriched microbes in the Mediterranean, together with the biotechnological potential of these sponges and their associated bacteria as sources of bioactive natural compounds.

Introduction Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. NMOSD starting after the age of 50 years is considered a “late onset” (LO-NMOSD) and seems to be particularly aggressive. The objective of this paper is to present a series of 37 Brazilian patients with LO-NMOSD. Methods Retrospective data collection from medical records of patients with LO-NMOSD seen at 14 Brazilian specialized units. Results The ratio of women to men in the sample was 4.3 to 1. The patients were followed up for a median period of 4 years. Sex, age at disease onset, and ethnic background were not associated with the number of relapses or disability outcomes. Extensive longitudinal myelitis affected 86% of patients, while optic neuritis affected 70%, and brainstem syndromes were present in only 16% of these patients. Six patients are currently using some type of support for walking or are wheelchair-bound. Three have died. Therapeutic options for NMOSD were particularly complicated for these elderly patients, since medications for controlling NMOSD are, in essence, immunosuppressive. Long-term use of corticosteroids can be an issue when the patients have high blood pressure, diabetes mellitus, or dyslipidemia (conditions often seen in elderly individuals). Conclusion This series of LO-NMOSD cases highlights the importance of prompt diagnosis and treatment for these patients.

Fingolimod is an effective therapy for multiple sclerosis (MS). Isolated reports of very aggressive MS rebound after discontinuation of fingolimod are drawing neurologists’ attention to this potentially severe complication of the drug. Our objective was to collect literature data on cases of MS rebound following fingolimod withdrawal. In addition, we report six new cases of this adverse event in Brazil. We carried out a systematic review of published data on cases of MS rebound after fingolimod was discontinued. In addition, the study reports a retrospective data series of Brazilian patients presenting this rebound reaction. Twenty papers have been published reporting on 52 patients with severe MS rebound after fingolimod withdrawal. Six new patients are included in the present paper, all of them with aggressive rebound and accumulated disability sequelae. We recommend gradual discontinuation of fingolimod with replacement by other treatment. The washout period should not exceed 4 weeks.

Made available in DSpace on 2020-12-10T17:01:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Construction of water diversions is a common response to the increasing demands for freshwater, often resulting in benefits to communities but with the risk of multiple environmental, economic, and social impacts. Water-diversion projects can favor massive introductions and accelerate biotic homogenization. This study provides empirical evidence on the consequences of a proposed law intended to divert water from two large and historically isolated river basins in Brazil: Tocantins to Sao Francisco. Compositional similarity (CS) and beta-diversity were quantified encompassing aquatic organisms: mollusks, zooplankton, crustaceans, insects, fishes, amphibians, reptiles, mammals, and plants. For CS we (i) considered only native species, and (ii) simulated the introduction of non-natives and assumed the extinction of threatened species due to this water-diversion project. We highlight the environmental risks of such large-scale projects, which are expected to cause impacts on biodiversity linked to bioinvasion and homogenization, and we recommend alternatives in order to solve water-demand conflicts. Univ Fed Parana, Setor Tecnol, Dept Engn Ambiental, LEC, BR-81531970 Curitiba, Parana, Brazil Univ Estadual Paulista, Dept Zool, BR-18618970 Sao Paulo, SP, Brazil Univ Fed Tocantins, Nucleo Estudos Ambientais, BR-77500000 Porto Nacl, Tocantins, Brazil INPA, BR-69067375 Manaus, Amazonas, Brazil Univ Fed Sao Carlos, Dept Hidrobiol, Ctr Ciencias Biol & Saude, BR-13565905 Sao Paulo, SP, Brazil Univ Estado Minas Gerais, Dept Ciencias Biol, Lab Hidrobiol, BR-37900106 Passos, MG, Brazil Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Biol, BR-14040901 Sao Paulo, SP, Brazil Univ Fed Espirito Santo, Dept Biol, Lab Genet & Evolucao Mol, BR-29075910 Vitoria, ES, Brazil Univ Fed Acre, Ctr Educ & Letras, Lab Etnociencias, BR-69980000 Cruzeiro Do Sul, Acre, Brazil Univ Fed Parana, Dept Bot, Lab Anal & Sintese Biodiversidade, Programa Posgrad Ecol & Conservacao, BR-81531970 Curitiba, Parana, Brazil Univ Estadual Paulista, Dept Zool, BR-18618970 Sao Paulo, SP, Brazil CAPES: 001 CNPq: 302367/2018-7 CNPq: 303776/2015-3 CNPq: 167382/2017-9 CNPq: 141028/2016-5

Graphene integrated photonics provides several advantages over conventional Si photonics. Single layer graphene (SLG) enables fast, broadband, and energy-efficient electro-optic modulators, optical switches and photodetectors (GPDs), and is compatible with any optical waveguide. The last major barrier to SLG-based optical receivers lies in the low responsivity - electrical output per optical input - of GPDs compared to conventional PDs. Here we overcome this shortfall by integrating a photo-thermoelectric GPD with a Si microring resonator. Under critical coupling, we achieve $>$90% light absorption in a $\sim$6 $��$m SLG channel along the Si waveguide. Exploiting the cavity-enhanced light-matter interaction, causing carriers in SLG to reach $\sim$400 K for an input power of $\sim$0.6 mW, we get a voltage responsivity $\sim$90 V/W, demonstrating the feasibility of our approach. Our device is capable of detecting data rates up to 20 Gbit/s, with a receiver sensitivity enabling it to operate at a 10$^{-9}$ bit-error rate, on par with mature semiconductor technology. The natural generation of a voltage rather than a current, removes the need for transimpedance amplification, with a reduction of the energy-per-bit cost and foot-print, when compared to a traditional semiconductor-based receiver., 11 pages, 5 figures

This study compared standard of care testing (SOC) to BioFire® FilmArray® Pneumonia plus Panel (PNplus). PNplus detects 15 bacteria with semiquantitative log bin values, 7 antibiotic resistance markers, three atypical bacteria (AB), and eight viral classes directly from bronchoalveolar lavage-like specimens (BLS) and sputum-like specimens (SLS). Fifty-two laboratories from 13 European countries and Israel tested 1234 BLS and 1242 SLS with PNplus and SOC. Detection rates and number of pathogens/samples were compared for PNplus pathogens. PNplus bin values and SOC quantities were compared. Three thousand two hundred sixty-two bacteria in PNplus were detected by PNplus and/or SOC. SOC detected 57.1% compared to 95.8% for PNplus (p ≤ 0.0001). PNplus semiquantitative bin values were less than SOC, equal to SOC, or greater than SOC in 5.1%, 25.4%, and 69.6% of results, respectively. PNplus bin values were on average ≥ 1 log than SOC values (58.5% 1–2 logs; 11.0% 3–4 logs). PNplus identified 98.2% of MRSA and SOC 55.6%. SOC detected 73/103 AB (70.9%) and 134/631 viruses (21.2%). PNplus detected 93/103 AB (90.3%) and 618/631 viruses (97.9%) (p ≤ 0.0001). PNplus and SOC mean number of pathogens/samples were 1.99 and 1.44, respectively. All gram-negative resistance markers were detected. PNplus and SOC results were fully or partially concordant for 49.1% and 26.4% of specimens, respectively. PNplus was highly sensitive and detected more potential pneumonia pathogens than SOC. Semiquantification may assist in understanding pathogen significance. As PNplus generates results in approximately 1 h, PNplus has potential to direct antimicrobial therapy in near real time and improve antimicrobial stewardship and patient outcomes.

Observational studies suggest that a heart failure (HF) diagnosis carries a poor prognosis in subjects with severe SARS-CoV2 (COVID-19) infection, but it is unknown whether this association reflects direct myocardial damage due to COVID-19 or the consequence of preexisting cardiac defects and related cardiovascular disease (CVD) risk burden. Although the close relation between CVD and COVID-19 outcomes is well established, contrasting data exists about the occurrence of HF complications during COVID-19 infection. Therefore, a specific algorithm focused on diagnostic differentiation in acute patients distinguishing between acute HF and acute respiratory distress syndrome related to COVID-19 is needed. Further, several concerns exist for the management of patients with an uncertain diagnosis and acute dyspnea, the exact relationship existing between COVID-19 and HF. Therefore, the treatment for subjects with both COVID-19 and HF and which criteria may be defined for domiciliary or hospital management, remain poorly defined. Herein, we describe practices to be adopted in order to address these concerns and avoid further virus spread among patients, l and their familiars involved in such patients’ care.

Vitamin K antagonists (VKA) are the most widely used anticoagulants in the world. An appropriate management of treated patients is crucial for their efficacy and safety. The prospective, observational, multicenter, inception-cohort FCSA-START Register, a branch of START Register (NCT02219984) included VKA-treated patients managed by centers of Italian Federation of anticoagulation clinics (AC). Baseline patient characteristics and data during treatment were analyzed and compared with those of ISCOAT study, performed by the Federation and published in 1996/7. 5707 naïve patients [53% males, mean age 73.0 years (28.1% >80 years)], 61.6% treated for atrial fibrillation (AF), and 28.0% for venous thromboembolism were included. During the 8906 patient-years (pt-yrs) of observation, 123 patients had major bleeding (MB) (1.38% pt-yrs; fatal: 0.11% pt-yrs), while non-major clinically relevant bleeds were 144 (1.62% pt-yrs). Bleeding was more frequent in elderly (≥70 years; p = 0.04), and during initial 3-month therapy (p = 0.02). Bleeding rate was 2.5% pt-yrs for temporally related INR results