Automatic Middle-Out Optimisation of Coarse-Grained Lipid Force Fields

Automatic data-driven approaches are increasingly used to develop accurate molecular models. But the parameters of such automatically-optimised models are typically untransferable. Using a multi-reference approach in combination with an automatic optimisation engine (SwarmCGM), here we show that it is possible to optimise coarse-grained (CG) lipid models that are also transferable, generating optimised lipid force fields. The parameters of the CG lipid models are iteratively and simultaneously optimised against higher-resolution simulations (bottom-up) and experimental data (top-down references). Including different types of lipid bilayers in the training set guarantees the transferability of the optimised force field parameters. Tested against state-of-the-art CG lipid force fields, we demonstrate that SwarmCGM can systematically improve their parameters, enhancing the agreement with the experiments even for lipid types not included in the training set. The approach is general and can be used to improve existing CG lipid force fields, as well as to develop new custom ones.Comment: Paper (Pages 1-16) + Supporting Information (Pages 17-40

COVID-19 as a Potential Cause of Muscle Injuries in Professional Italian Serie A Soccer Players: A Retrospective Observational Study

the COVID-19 pandemic has shocked the entire planet. the soccer world has also suffered major upheavals, and many professional soccer players have been infected with the virus. The aim of this study was to evaluate the incidence of injuries in Italian Serie A professional soccer players before and during the COVID-19 pandemic. methods: we evaluated the incidence of muscle injuries between four competitive seasons of the Italian Serie A (2016-2017, 2017-2018, and 2018-2019 pre-COVID-19 vs. 2020/2021 post-COVID-19) in professional soccer players. results: significant differences were found in muscular injuries between the post-COVID-19 season and the previous seasons (p < 0.001). The median split of the players' positivity duration was of 15 days. The players' long positivity (PLP) group showed a significant number of muscular injuries compared to the players' short positivity (PSP) group (p < 0.0014, ES = 0.81, large). the total teams' days of positivity were significantly related to the total team number of muscular injuries (r = 0.86; CI 95% 0.66 to 0.94; p < 0.0001). In conclusion, this data showed that the competitive season post-COVID-19 lockdown has a higher incidence of muscle injuries in Italian serie a soccer players compared to the pre-pandemic competitive season

Mechanical Ventilation in Patients with End-Stage Idiopathic Pulmonary Fibrosis

Background: Acute respiratory failure (ARF) occurring during idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis. In this subset of individuals, mechanical ventilation (MV) may be required. Objectives: We analysed the characteristics of a group of IPF patients undergoing MV for ARF in order to give some indications on the supposed prognosis. Methods: Hospital records of 34 consecutive patients with IPF, who underwent MV for ARF, were retrospectively examined. Demographic data, time from diagnosis, gas exchange, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ARF causes and MV failure were recorded. Results: Fifteen subjects (group A) underwent invasive MV and 19 patients (group B) non-invasive ventilation (NIV). The 2 groups were different for disease severity (APACHE II score 24.2 ± 6 vs. 19.5 ± 5.9; p = 0.01). Both ventilatory strategies temporarily increased PaO2/FiO2 as compared with spontaneous breathing (group A: 148.5 ± 52 vs. 99 ± 39, p = 0.0004; group B: 134 ± 36 vs. 89 ± 26, p = 0.0004). NIV reduced the respiratory rate (26 ± 7 vs. 36 ± 9 with spontaneous breathing; p = 0.002). Duration of MV correlated with the time of evolution of IPF (r = 0.45; p = 0.018). The in-hospital mortality rate was 85% (100% for invasive MV, 74% for NIV). Four of the 5 survivors died within 6 months from hospital discharge (range 2–6 months). Conclusions: MV does not appear to have a significant impact on the survival of patients with end-stage IPF. NIV may be useful for compassionate use, providing relief from dyspnoea and avoiding aggressive approaches

Automatic Optimization of Lipid Models in the Martini Force Field Using SwarmCG.

After two decades of continued development of the Martini coarse-grained force field (CG FF), further refinment of the already rather accurate Martini lipid models has become a demanding task that could benefit from integrative data-driven methods. Automatic approaches are increasingly used in the development of accurate molecular models, but they typically make use of specifically designed interaction potentials that transfer poorly to molecular systems or conditions different than those used for model calibration. As a proof of concept, here, we employ SwarmCG, an automatic multiobjective optimization approach facilitating the development of lipid force fields, to refine specifically the bonded interaction parameters in building blocks of lipid models within the framework of the general Martini CG FF. As targets of the optimization procedure, we employ both experimental observables (top-down references: area per lipid and bilayer thickness) and all-atom molecular dynamics simulations (bottom-up reference), which respectively inform on the supra-molecular structure of the lipid bilayer systems and on their submolecular dynamics. In our training sets, we simulate at different temperatures in the liquid and gel phases up to 11 homogeneous lamellar bilayers composed of phosphatidylcholine lipids spanning various tail lengths and degrees of (un)saturation. We explore different CG representations of the molecules and evaluate improvements a posteriori using additional simulation temperatures and a portion of the phase diagram of a DOPC/DPPC mixture. Successfully optimizing up to ∼80 model parameters within still limited computational budgets, we show that this protocol allows the obtainment of improved transferable Martini lipid models. In particular, the results of this study demonstrate how a fine-tuning of the representation and parameters of the models may improve their accuracy and how automatic approaches, such as SwarmCG, may be very useful to this end. </p

Prevalence of metabolic syndrome and of symptoms of anxiety and depression in patients undergoing colonoscopy

Introduction Metabolic syndrome (MetS) is defined by metabolic and cardio-vascular impairments and is frequently associated with anxiety and depressive disorders. Both MetS and anxiety-depressive syndromes feature similar systemic inflammatory alterations. Inflammation of the large bowel is also a key factor for the development of colorectal cancer (CRC). Objective To measure the prevalence of MetS and symptoms of anxiety and depression among patients undergoing colonoscopy. Methods Cross-sectional study. Patients undergoing colonoscopy aged 40 or more, with negative history for neoplasia or inflammatory bowel disease, were enrolled. Data collected: colonoscopy outcome, presence/absence of MetS (IDF and ATP III criteria), presence/absence of depressive and anxiety symptoms assessed with HADS. Results The sample was made up of 53 patients (female 24, 45.3%). Mean age was 60.66 ± 9.08. At least one adenoma was found to 23 patients (43.3%). Prevalence of MetS ranged from 34% to 36% (ATP III and IDF criteria, respectively). Prevalence of depressive and anxiety symptoms was 20% and 33%, respectively. Conclusion Prevalence of MetS, anxiety and depressive symptoms among patients undergoing colonoscopy was higher than in the general population

Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis

Almost 25% of lung cancers (LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two parameters may improve their prognosis. Sixty-eight never-smokers LC patients with high or low CRP were selected. The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the human leukocyte antigens (HLA-DR and HLA-I), CD8, CD4, CD3, CD33, CD163, and CD68 were evaluated by immunohistochemistry on surgical samples given TIC evaluation. The classification model based on TIC scores was generated by Classification and Regression Tree analysis. Tumor mutational burden was evaluated by targeted next-generation sequencing. Exclusively high CRP (H-CRP) subset showed PD-L1 expression in 35% of LC as well as lower HLA-I and HLA-DR in their stromal cells. CD3, CD4, CD8, HLA-I, HLA-DR tumor cells staining were associated with a "low inflammatory profile" subset. CRP and LC immune profiles drive clinical outcome: 5-year survival 88% against 8% was associated with low and high-risk profiles (p&lt; 0.0001). Clinical outcome prediction in never-smoker LC patients may be improved by both CRP and tumor immune contexture evaluation

Cardiovascular risk factors, anxiety symptoms and inflammation markers: Evidence of association from a cross-sectional study

Introduction Anxiety disorders and Cardiovascular (CV) diseases, among the most common disorders in Western World, are often comorbid. A chronic systemic inflammatory state might be a shared underlining pathophysiological mechanism. Aims To investigate the association between anxiety symptoms, CV risks factors and inflammatory markers in an outpatient sample. Methods Cross-sectional study. Inclusion criteria: outpatients aged ≥40 years, attending colonoscopy after positive faecal occult blood test, negative medical history for cancer. Collected data: blood pressure, glycaemia, lipid profile, waist circumference, BMI, PCR (C Reactive Protein), LPS (bacterial Lipopolysaccharide). Psychometric tests: HADS, TCI, IMSA, SF36. Statistical analysis performed with STATA13. Results Fifty four patients enrolled (27 males, 27 females). Sixteen patients (30.19%) were positive for anxiety symptoms. Thirty-three patients (61.11%) had hypertension, 14 (25.93%) hyperglycaemia and 64.81% were overweight, with frank obesity (BMI≥ 30) in 11 subjects (20.37%). Anxiety symptoms were associated with low hematic HDL values (OR = 0.01; P = 0.01) and high concentration of triglycerides (OR = 0.023; P = 0.02) at the multiple regression model. At the univariate logistic analysis, anxiety was associated with LPS (OR = 1.06; P = 0.04). Conclusions Further evidence over the epidemiological link between common mental disorders and CV diseases was collected, with possible hints on pathophysiology and causative mechanisms related to inflammation. The importance of screening for anxiety and depression in medical populations is confirmed. Suggestions on future availability of screening tools based on inflammatory-related indicators should be the focus of future research

Residual Site Radiotherapy After Immunochemotherapy in Primary Mediastinal B-Cell Lymphoma: A Monoinstitutional Retrospective Study

Aim: To evaluate the efficacy of residual site radiation therapy (RSRT) on local control (LC), progressionfree (PFS) and overall (OS) survival in patients with primary mediastinal lymphoma (PMBCL), following rituximab and chemotherapy treatment (ICHT). Patients and Methods: The study included 34 patients with PMBCL treated between 2006 and 2014 with ICHT with/without autologous stem cell transplantation and RSRT. Between the end of ICHT/stem cell transplantation and RSRT, patients were evaluated with F-18-fluorodeoxyglucose positron-emission tomography. The gross tumor volume included morphological mediastinal residual disease after ICHT/SCT. The percentage of LC, PFS and OS were assessed. Results: All patients received RSRT with a median dose of 30 Gy. Median follow-up was 82 months. One patient out of 34 (3%) showed progressive disease 9 months from diagnosis. The 10-year PFS and OS were 97% and 97% respectively. Conclusion: RSRT in patients with PMBCL treated with ICHT did not impact unfavorably on LC and patient survival

Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM)

: The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended