A Novel Gaussian Extrapolation Approach for 2D Gel Electrophoresis Saturated Protein Spots

Analysis of images obtained from two-dimensional gel electrophoresis (2D-GE) is a topic of utmost importance in bioinformatics research, since commercial and academic software available currently has proven to be neither completely effective nor fully automatic, often requiring manual revision and refinement of computer generated matches. In this work, we present an effective technique for the detection and the reconstruction of over-saturated protein spots. Firstly, the algorithm reveals overexposed areas, where spots may be truncated, and plateau regions caused by smeared and overlapping spots. Next, it reconstructs the correct distribution of pixel values in these overexposed areas and plateau regions, using a two-dimensional least-squares fitting based on a generalized Gaussian distribution. Pixel correction in saturated and smeared spots allows more accurate quantification, providing more reliable image analysis results. The method is validated for processing highly exposed 2D-GE images, comparing reconstructed spots with the corresponding non-saturated image, demonstrating that the algorithm enables correct spot quantificatio

Linear Operator Inequality and Null Controllability with Vanishing Energy for unbounded control systems

We consider linear systems on a separable Hilbert space $H$, which are null controllable at some time $T_0>0$ under the action of a point or boundary control. Parabolic and hyperbolic control systems usually studied in applications are special cases. To every initial state $y_0 \in H$ we associate the minimal "energy" needed to transfer $y_0$ to $0$ in a time $T \ge T_0$ ("energy" of a control being the square of its $L^2$ norm). We give both necessary and sufficient conditions under which the minimal energy converges to $0$ for $T\to+\infty$. This extends to boundary control systems the concept of null controllability with vanishing energy introduced by Priola and Zabczyk (Siam J. Control Optim. 42 (2003)) for distributed systems. The proofs in Priola-Zabczyk paper depend on properties of the associated Riccati equation, which are not available in the present, general setting. Here we base our results on new properties of the quadratic regulator problem with stability and the Linear Operator Inequality.Comment: In this version we have also added a section on examples and applications of our main results. This version is similar to the one which will be published on "SIAM Journal on Control and Optimization" (SIAM

A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia

Introduction Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process. The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. The dose and safety of reparixin have been investigated in clinical trials of patients with metastatic breast cancer. Methods This was a phase 2, open-label, multicenter, randomized study in hospitalized adult patients with severe COVID-19 pneumonia from May 5, 2020 until November 27, 2020. Patients were randomized 2:1 to receive 1200 mg reparixin orally three times daily or standard of care (SOC) for up to 21 days. The primary endpoint was defined as a composite of clinical events: use of supplemental oxygen, need for mechanical ventilation, intensive care unit admission, and/or use of rescue medication. Results Fifty-five patients were enrolled between reparixin (n = 36) and SOC (n = 19). The rate of clinical events was statistically significantly lower in the reparixin group compared with the SOC group (16.7% [95% CI 6.4-32.8%] vs. 42.1% [95% CI 20.3-66.5%], P = 0.02). The sensitivity analysis based on the Cox regression model provided an adjusted hazard ratio of 0.33 with statistical significance lower than 0.05 (95% CI 0.11-0.99; P = 0.047). Reparixin treatment appeared to be well tolerated. Conclusion In patients with severe COVID-19, reparixin led to an improvement in clinical outcomes when compared with the SOC. A larger phase 3 clinical study is needed to confirm these results

Parkinson's disease plasma biomarkers: An automated literature analysis followed by experimental validation

Diagnosis of Parkinson's disease (PD) is currently assessed by the clinical evaluation of extrapyramidal signs. The identification of specific biomarkers would be advisable, however most studies stop at the discovery phase, with no biomarkers reaching clinical exploitation. To this purpose, we developed an automated literature analysis procedure to retrieve all the background knowledge available in public databases. The bioinformatic platform allowed us to analyze more than 51,000 scientific papers dealing with PD, containing information on 4121 proteins. Out of these, we could track back 35 PD-related proteins as present in at least two published 2-DE maps of human plasma. Then, 9 different proteins (haptoglobin, transthyretin, apolipoprotein A-1, serum amyloid P component, apolipoprotein E, complement factor H, fibrinogen γ, thrombin, complement C3) split into 32 spots were identified as a potential diagnostic pattern. Eventually, we compared the collected literature data to experimental gels from 90 subjects (45 PD patients, 45 non-neurodegenerative control subjects) to experimentally verify their potential as plasma biomarkers of PD

Study of the K+- to pi+- gamma gamma decay by the NA62 experiment

A study of the dynamics of the rare decay $K^\pm\to\pi^\pm\gamma\gamma$ has been performed on a sample of 232 decay candidates, with an estimated background of $17.4\pm1.1$ events, collected by the NA62 experiment at CERN in 2007. The results are combined with those from a measurement conducted by the NA48/2 collaboration at CERN. The combined model-independent branching ratio in the kinematic range $z=(m_{\gamma\gamma}/m_K)^2>0.2$ is ${\cal B}_{\rm MI}(z>0.2) = (0.965 \pm 0.063) \times 10^{-6}$, and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is ${\cal B}(K_{\pi\gamma\gamma}) = (1.003 \pm 0.056) \times 10^{-6}$. A detailed comparison of the results with the previous measurements is performed.A study of the dynamics of the rare decay $K^\pm\to\pi^\pm\gamma\gamma$ has been performed on a sample of 232 decay candidates, with an estimated background of $17.4\pm1.1$ events, collected by the NA62 experiment at CERN in 2007. The results are combined with those from a measurement conducted by the NA48/2 collaboration at CERN. The combined model-independent branching ratio in the kinematic range $z=(m_{\gamma\gamma}/m_K)^2>0.2$ is ${\cal B}_{\rm MI}(z>0.2) = (0.965 \pm 0.063) \times 10^{-6}$, and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is ${\cal B}(K_{\pi\gamma\gamma}) = (1.003 \pm 0.056) \times 10^{-6}$. A detailed comparison of the results with the previous measurements is performed.A study of the dynamics of the rare decay K±→π±γγ has been performed on a sample of 232 decay candidates, with an estimated background of 17.4±1.1 events, collected by the NA62 experiment at CERN in 2007. The results are combined with those from a measurement conducted by the NA48/2 Collaboration at CERN. The combined model-independent branching ratio in the kinematic range z=(mγγ/mK)2>0.2 is BMI(z>0.2)=(0.965±0.063)×10−6 , and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is B(Kπγγ)=(1.003±0.056)×10−6 . A detailed comparison of the results with the previous measurements is performed

Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe