On Compressing Collections of Substring Samples

Publisher Copyright: © 2022 Copyright for this paper by its authors. Use permitted under Creative Commons License Attribution 4.0 International (CC BY 4.0).Given a string X = X[1..n] of length n, and integers m and s, such that n > m ≥ 2s > 0, we consider the problem of compressing the string S formed by concatenating the substrings of X of length m starting at positions i ≡ 1 (mod s). In particular, we provide an upper bound of (2n − m)/s + 2z + (m − s) on the size of the Lempel-Ziv (LZ77) parsing of S, where z is the size of the parsing of X. We also show that a related bound holds regardless of the order in which the substrings are concatenated in the formation of S. If X is viewed as a genome sequence, the above substring sampling process corresponds to an idealized model of short read DNA sequencing.Peer reviewe

Pratiche per l’insegnamento adattivo nelle discipline STEAM: il Progetto T.E.S.T.

Il superamento della pandemia da Covid-19 ha impresso una spinta propulsiva per ripensare i modelli didattici dell’insegnamento nelle STEAM, orientando la ricerca scientifica verso la costruzione di repertori metodologici di tipo learner-centered e inquiry-based, in grado di valorizzare l’apprendimento attraverso l’esperienza in contesti ad alto tasso di tecnologizzazione. A fronte di questo scenario, l’articolo presenta i risultati del primo segmento qualitativo-esplorativo del progetto di ricerca biennale T.E.S.T. - Technologies for STEAM Teaching. Delinea l’impianto metodologico del progetto, che ha consentito la costruzione di un repertorio metodologico per l’insegnamento adattivo e accessibile nelle STEAM, in fase di sperimentazione nelle otto università partner del progetto. Il focus verte sulle caratteristiche del profilo emergente del “docente adattivo” e sulle dimensioni progettuali dell’insegnamento adattivo nelle discipline STEAM (Barana et al. 2019; Hardy et al., 2019)

Impact of ABCG2 and ABCB1 Polymorphisms on Imatinib Plasmatic Exposure: An Original Work and Meta-Analysis

Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML) patients. Imatinib is a substrate of the drug transporters ATP-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) that can affect its plasma concentration. In the present study, the association between three genetic polymorphisms in ABCB1 (rs1045642, rs2032582, rs1128503) and one in ABCG2 (rs2231142) and the imatinib plasma trough concentration (Ctrough) was investigated in 33 GIST patients enrolled in a prospective clinical trial. The results of the study were meta-analyzed with those of other seven studies (including a total of 649 patients) selected from the literature through a systematic review process. The ABCG2 c.421C>A genotype demonstrated, in our cohort of patients, a borderline association with imatinib plasma trough levels that became significant in the meta-analysis. Specifically, homozygous carriers of the ABCG2 c.421 A allele showed higher imatinib plasma Ctrough with respect to the CC/CA carriers (Ctrough, 1463.2 ng/mL AA, vs. 1196.6 ng/mL CC + AC, p = 0.04) in 293 patients eligible for the evaluation of this polymorphism in the meta-analysis. The results remained significant under the additive model. No significant association could be described between ABCB1 polymorphisms and imatinib Ctrough, neither in our cohort nor in the meta-analysis. In conclusion, our results and the available literature studies sustain an association between ABCG2 c.421C>A and imatinib plasma Ctrough in GIST and CML patients

Association of ADME gene polymorphisms on toxicity to CDK4/6 inhibitors in patients with HR+ HER2- metastatic breast cancer

: A wide interindividual variability in therapeutic response to cyclin-dependent kinases 4 and 6 inhibitors (CDKis) palbociclib, ribociclib and abemaciclib, among patients with HR+/HER2- metastatic breast cancer has been reported. This study explored the impact of genetic polymorphisms in ADME genes (responsible for drug absorption, distribution, metabolism, and elimination) on CDKis safety profiles in 230 patients. Selected endpoints include grade 3/4 neutropenia at day 14 of the first treatment cycle, early dose-limiting toxicities (DLTs), and dose reductions within the initial three cycles. Our analysis revealed associations between these endpoints and polymorphisms in CYP3A4, CYP3A5, ABCB1, and ABCG2 genes. Their impact on CDKis plasma concentrations (Ctrough) was also examined. Specifically, ABCB1 c.1236C>T and c.2677C>T polymorphisms correlated significantly with grade 3/4 neutropenia at day 14 (OR 3.94, 95% CI 1.32-11.75; p = 0.014 and OR 3.32, 95% CI 1.12-9.85; p = 0.030). Additionally, ABCB1 c.3435C>T was associated with an elevated risk of early DLTs and dose reductions (OR 3.28, 95% CI 1.22-8.84, p = 0.019; OR 2.60, 95% CI 1.20-5.60, p = 0.015). Carriers of the CYP3A4*22 allele also demonstrated in univariate a higher risk of early DLTs (OR 3.10, 95% CI 1.01-9.56, p = 0.049). Furthermore, individuals with the ABCB1 1236T-3435T-2677T(A) variant haplotype exhibited significant associations with grade 3/4 neutropenia at day 14 (OR 3.36, 95% CI 1.20-9.41; p = 0.021) and early DLTs in univariate (OR 3.08, 95% CI 1.19-7.95; p = 0.020). Homozygous carriers of the ABCB1 T-T-T(A) haplotype tended to have a higher mean ribociclib Ctrough (934.0 ng/mL vs. 752.0 ng/mL and 668.0 ng/mL). Regardless preliminary, these findings offer promising insights into the role of pharmacogenetic markers in CDKis safety profiles, potentially contributing to address the interindividual variability in CDKis responses

Surveying volcanic crises exercises: From open-question questionnaires to a prototype checklist

Volcanic crisis exercises are usually run to test response capabilities, communication protocols, and decision-making procedures by agencies with responsibilities to cope with scenarios of volcanic unrest with inherent uncertainty, such as volcano observatories and/or civil protection authorities. During the last decades, the use of questionnaires has been increased to evaluate people's knowledge on volcanic hazards and their perception of risk, to better understand their preparedness to respond to emergency measures plans. In this paper, we present a study carried out within the European Network of Observatories and Research Infrastructures for Volcanology project (EUROVOLC) focused on extracting information on the experience gained during volcanic-crisis exercises by the project's participants and beyond. An open-ended question questionnaire was firstly distributed for a survey within the project community. Through the results obtained, we developed a user-friendly online multi-choice questionnaire that was submitted to the volcanological communities within and outside EUROVOLC. Analyzing the answers to the online questionnaire, we extracted a prototype checklist for guiding the design of such exercises in the future. Our results confirm this type of survey as a very useful tool for gathering information on participants' experience and knowledge, able to understand which data and information may be useful when designing exercises for scientists, emergency managers and decision makers. In particular, the main lessons learnt regard the need i) to increase training activities involving people exposed to volcanic hazards and media, ii) to improve external communication tools (between players and public/media), equipment and protocols and iii) to better define decision-makers' needs

"Diagnosis on the Dock" project: A proactive screening program for diagnosing pulmonary tuberculosis in disembarking refugees and new SEI model.

Abstract Objective From 2011 to 2017, the total number of refugees arriving in Europe, particularly in Italy, climbed dramatically. Our aim was to diagnose pulmonary TB in migrants coming from the African coast using a clinical-based port of arrival (PoA) screening program. Methods From 2016 to 2018, migrants coming via the Mediterranean Route were screened for body temperature and the presence of cough directly on the dock: if they were feverish with productive cough, their sputum was examined with NAAT; with a dry cough, they underwent Chest-X-ray (CXR). Those migrants with positive NAAT or CXR suggestive for TB were admitted to our ward. In addition, we plotted an SEI simulation of our project to evaluate the epidemiological impact of our screening. Results Out of 33.676 disembarking migrants, 314 (0.9%) had fever and cough: 80 (25.47%) with productive cough underwent NAAT in sputum, and 16 were positive for TB; 234 (74.52%) with dry cough had a CXR examination, and 39 were suggestive of TB, later confirmed by mycobacterial culture. The SEI-new model analysis demonstrated that our screening program significantly reduced TB spreading all over the country. Conclusions For possible future high migrant flows, PoA screening for TB has to be considered feasible and effective in decreasing TB spreading

Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas

Simple Summary This clinical investigation reports the results of a prospective, multicenter phase II trial designed to evaluate the activity and safety of combining non-pegylated liposomal doxorubicin (NPLD) with ifosfamide as a first-line treatment for advanced/metastatic STS. The study results demonstrate a remarkable overall response rate (ORR) alongside a satisfactory disease control rate (DCR) while maintaining acceptable levels of toxicity. The addition of NPLD to ifosfamide, showing high activity and a low toxicity profile, makes this drug combination a useful option for patients with advanced/metastatic STS. These findings provide a promising basis for further comprehensive research into the clinical application of this drug combination in this disease setting.Abstract Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand-foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m2) on day 1 along with ifosfamide (3000 mg/m2 on days 1, 2, and 3 with equidose MESNA) administered every 3 weeks. The overall response rate, yielding 40% (95% CI: 0.29-0.51), resulted in statistical significance; the disease control rate stood at 81% (95% CI: 0.73-0.90), while only 16% (95% CI: 0.08-0.24) of patients experienced a progressive disease. These findings indicate that the combination of NPLD and ifosfamide yields a statistically significant response rate in advanced/metastatic STS with limited toxicity

Oncological care organisation during COVID-19 outbreak

Funding: This work was supported by Fonds de la Recherche Scientifique (grant to CEO) and Fondation Léon Fredericq (grant to GJ and CEO).Background: COVID-19 appeared in late 2019, causing a pandemic spread. This led to a reorganisation of oncology care in order to reduce the risk of spreading infection between patients and healthcare staff. Here we analysed measures taken in major oncological units in Europe and the USA. Methods: A 46-item survey was sent by email to representatives of 30 oncological centres in 12 of the most affected countries. The survey inquired about preventive measures established to reduce virus spread, patient education and processes employed for risk reduction in each oncological unit. Results: Investigators from 21 centres in 10 countries answered the survey between 10 April and 6 May 2020. A triage for patients with cancer before hospital or clinic visits was conducted by 90.5% of centres before consultations, 95.2% before day care admissions and in 100% of the cases before overnight hospitalisation by means of phone calls, interactive online platforms, swab test and/or chest CT scan. Permission for caregivers to attend clinic visits was limited in many centres, with some exceptions (ie, for non-autonomous patients, in the case of a new diagnosis, when bad news was expected and for terminally ill patients). With a variable delay period, the use of personal protective equipment was unanimously mandatory, and in many centres, only targeted clinical and instrumental examinations were performed. Telemedicine was implemented in 76.2% of the centres. Separated pathways for COVID-19-positive and COVID-19-negative patients were organised, with separate inpatient units and day care areas. Self-isolation was required for COVID-19-positive or symptomatic staff, while return to work policies required a negative swab test in 76.2% of the centres. Conclusion: Many pragmatic measures have been quickly implemented to deal with the health emergency linked to COVID-19, although the relative efficacy of each intervention should be further analysed in large observational studies