New error measures and methods for realizing protein graphs from distance data

The interval Distance Geometry Problem (iDGP) consists in finding a realization in $\mathbb{R}^K$ of a simple undirected graph $G=(V,E)$ with nonnegative intervals assigned to the edges in such a way that, for each edge, the Euclidean distance between the realization of the adjacent vertices is within the edge interval bounds. In this paper, we focus on the application to the conformation of proteins in space, which is a basic step in determining protein function: given interval estimations of some of the inter-atomic distances, find their shape. Among different families of methods for accomplishing this task, we look at mathematical programming based methods, which are well suited for dealing with intervals. The basic question we want to answer is: what is the best such method for the problem? The most meaningful error measure for evaluating solution quality is the coordinate root mean square deviation. We first introduce a new error measure which addresses a particular feature of protein backbones, i.e. many partial reflections also yield acceptable backbones. We then present a set of new and existing quadratic and semidefinite programming formulations of this problem, and a set of new and existing methods for solving these formulations. Finally, we perform a computational evaluation of all the feasible solver$+$formulation combinations according to new and existing error measures, finding that the best methodology is a new heuristic method based on multiplicative weights updates

A Learning-based Mathematical Programming Formulation for the Automatic Configuration of Optimization Solvers

We propose a methodology, based on machine learning and optimization, for selecting a solver configuration for a given instance. First, we employ a set of solved instances and configurations in order to learn a performance function of the solver. Secondly, we formulate a mixed-integer nonlinear program where the objective/constraints explicitly encode the learnt information, and which we solve, upon the arrival of an unknown instance, to find the best solver configuration for that instance, based on the performance function. The main novelty of our approach lies in the fact that the configuration set search problem is formulated as a mathematical program, which allows us to a) enforce hard dependence and compatibility constraints on the configurations, and b) solve it efficiently with off-the-shelf optimization tools

Comparing perspective reformulations for piecewise-convex optimization

Our study is motivated by the solution of Mixed-Integer Non-Linear Programming (MINLP) problems with separable non-convex functions via the Sequential Convex MINLP technique, an iterative method whose main characteristic is that of solving, for bounding purposes, piecewise-convex MINLP relaxations obtained by identifying the intervals in which each univariate function is convex or concave and then relaxing the concave parts with piecewise-linear relaxations of increasing precision. This process requires the introduction of new binary variables for the activation of the intervals where the functions are defined. In this paper we compare the three different standard formulations for the lower bounding subproblems and we show, both theoretically and computationally, that -- unlike in the piecewise-linear case -- they are not equivalent when the perspective reformulation is applied to reinforce the formulation in the segments where the original functions are convex

Impact of COVID-19 pandemic on 2-[18F]FDG PET/CT imaging work-flow in a single medical institution: comparison among the three Italian waves

Purpose: To compare the impact of COVID-19 pandemic on 2-[18F]FDG PET/CT imaging work-flow during the three waves in a medical institution of southern of Italy. Methods: We retrospectively reviewed the numbers and results of 2-[18F]FDG PET/CT studies acquired during the following three periods of the COVID-19 waves: 1) February 3-April 30, 2020; 2) October 15, 2020–January 15, 2021; and 3) January 18-April 16, 2021. Results: A total of 861 PET/CT studies in 725 patients (388 men, mean age 64 +/- 4 years) was acquired during the three waves of COVID-19 pandemic. The majority (94%) was performed for diagnosis/staging (n = 300) or follow-up (n = 512) of neoplastic diseases. The remaining 49 studies (6%) were acquired for non-oncological patients. The distribution of number and type of clinical indications for PET/CT studies in the three waves were comparable (p < 0.06). Conversely, the occurrence of patients positive for COVID-19 infection progressively increased (p < 0.0001) from the first to third wave; in particular, patients with COVID-19 had active infection before PET/CT study as confirmed by molecular oro/nasopharyngeal swab. Conclusion: Despite the restrictive medical measures for the emergency, the number of 2-[18F]FDG PET/CT studies was unchanged during the three waves guaranteeing the diagnostic performance of PET/CT imaging for oncological patients

Mortality and heart rate in the elderly: role of cognitive impairment

Mortality related to heart rate ( HR) increase in the elderly has not yet been well established. To ascertain the relationships among cognitive impairment ( CI), mortality, and HR increase, the authors prospectively studied a random sample of elderly subjects stratified according to presence or absence of CI. Elderly subjects randomly selected in 1991 ( n = 1332) were followed up for 12 years. Mortality was established in 98.1% of the subjects. When HR was stratified in quartiles (&lt; 69,70-75,76-80, and &gt; 80 bpm), mortality was linearly associated with increased HR in all ( from 47.7 to 57.0; r(2) = .43, p = .019) and in subjects without ( from 41.7 to 51.1%; r(2) = .50, p = .043) but not in those with CI ( from 57.5 to 66.1; r(2) = .20, p = .363). Cox regression analysis, adjusted for several variables, shows that HR doesn't predict mortality in all subjects ( RR 0.69; 95% CI = 0.27-1.73) or in those with CI ( RR 0.91; 95% CI = 0.81-1.02). In contrast, HR predicts mortality in subjects without CI ( RR 1.10; 95% CI = 1.00-1.22). Hence, HR increase is a predictor of mortality in elderly subjects without CI. However, when considering all elderly subjects and those with CI, HR increase seems to have no effect on mortality. Thus, CI should be considered when focusing on HR increase as risk factor for mortality in the elderly

Liposomal doxorubicin supercharge-containing front-line treatment in patients with advanced-stage diffuse large B-cell lymphoma or classical Hodgkin lymphoma: Preliminary results of a single-centre phase II study

We evaluated the impact of liposomal doxorubicin (NPLD) supercharge-containing therapy on interim fluorodeoxyglucose positron emission tomography (interim-FDG-PET) responses in high-risk diffuse large B-cell lymphoma (DLBCL) or classical Hodgkin lymphoma (c-HL). In this phase II study (2016-2021), 81 adult patients with advanced-stage DLBCL (n&nbsp;=&nbsp;53) and c-HL (n&nbsp;=&nbsp;28) received front-line treatment with R-COMP-dose-intensified (DI) and MBVD-DI. R-COMP-DI consisted of 70 mg/m2 of NPLD plus standard rituximab, cyclophosphamide, vincristine and prednisone for three cycles (followed by three cycles with NPLD de-escalated at 50 mg/m2 ); MBVD-DI consisted of 35 mg/m2 of NPLD plus standard bleomycin, vinblastine and dacarbazine for two cycles (followed by four cycles with NPLD de-escalated at 25 mg/m2 ). Patients underwent R-COMP-DI and MBVD-DI with a median dose intensity of 91% and 94% respectively. At interim-FDG-PET, 72/81 patients (one failed to undergo interim-FDG-PET due to early death) had a Deauville score of ≤3. At end of treatment, 90% of patients reached complete responses. In all, 20 patients had Grade ≥3 adverse events, and four of them required hospitalisation. At a median 21-months of follow-up, the progression-free survival of the entire population was 77.3% (95% confidence interval 68%-88%). Our data suggest that the NPLD supercharge-driven strategy in high-risk DLBCL/c-HL may be a promising option to test in phase III trials, for improving negative interim-FDG-PET cases incidence