A quantum-inspired classifier for clonogenic assay evaluations.

Recent advances in Quantum Machine Learning (QML) have provided benefits to several computational processes, drastically reducing the time complexity. Another approach of combining quantum information theory with machine learning-without involving quantum computers-is known as Quantum-inspired Machine Learning (QiML), which exploits the expressive power of the quantum language to increase the accuracy of the process (rather than reducing the time complexity). In this work, we propose a large-scale experiment based on the application of a binary classifier inspired by quantum information theory to the biomedical imaging context in clonogenic assay evaluation to identify the most discriminative feature, allowing us to enhance cell colony segmentation. This innovative approach offers a two-fold result: (1) among the extracted and analyzed image features, homogeneity is shown to be a relevant feature in detecting challenging cell colonies; and (2) the proposed quantum-inspired classifier is a novel and outstanding methodology, compared to conventional machine learning classifiers, for the evaluation of clonogenic assays

Breast cancer cells treated with proton beam: Immunological features and gene signatures

The breast cancer (BC) disease is characterized by a wide heterogeneity at both clinical and molecular level, showing distinct subtypes with different clinical outcomes. Thus, the choice of the therapeutic plan, such as the type of radiotherapy (RT) need to take into account this complexity. Indeed, the proton therapy (PT) shows a medical benefit compared to conventional X-ray RT, as regards the localized delivery of the radiation dose sparing health tissues, but few data regarding proton-induced molecular changes are currently available. The aim of this study was therefore to investigate the production of immunological molecules and gene expression profiles induced by proton irradiation on BC cell lines. Clonogenic survival assay, luminex assay and cDNA microarray gene expression analyses were performed both in the non-tumorigenic MCF10A cell line and in two tumorigenic MCF7 and MDA-MB-231 cell lines, following irradiation with 0.5, 2 and 9 Gy of clinical proton beams. We found that proton irradiation induced gene expression changes useful to define a cell line and dose-dependent gene signatures. The lack of molecular data in the literature can be filled by data here presented that could represent a useful tool to better understand the molecular mechanisms elicited by protons predicting the treatment outcome

Preliminary study of novel SRC tyrosine kinase inhibitor and proton therapy combined effect on glioblastoma multiforme cell line: In vitro evaluation of target therapy for the enhancement of protons effectiveness

The aim of this work was to evaluate proton therapy effectiveness in combination with a molecule SRC protein inhibitor for glioblastoma multiforme treatment. The role of this novel compound, Si306, is to interfere with glioblastoma carcinogenesis and progression, creating a radiosensitivity condition. The experiments were performed on U87 human glioblastoma multiforme cell line. Molecule concentrations of 10 μM and 20μM were tested in combination with proton irradiation doses of 2, 4, 10 and 21Gy. Cell survival evaluation was performed by clonogenic assay. The results showed that Si306 increases the efficacy of proton therapy reducing the surviving cells fraction significantly compared to treatment with protons only. These studies will support the preclinical phase realization, in order to evaluate proton therapy effects and molecularly targeted drug combined treatments

Proton-irradiated breast cells: molecular points of view

Breast cancer (BC) is the most common cancer in women, highly heterogeneous at both the clinical and molecular level. Radiation therapy (RT) represents an efficient modality to treat localized tumor in BC care, although the choice of a unique treatment plan for all BC patients, including RT, may not be the best option. Technological advances in RT are evolving with the use of charged particle beams (i.e. protons) which, due to a more localized delivery of the radiation dose, reduce the dose administered to the heart compared with conventional RT. However, few data regarding proton-induced molecular changes are currently available. The aim of this study was to investigate and describe the production of immunological molecules and gene expression profiles induced by proton irradiation. We performed Luminex assay and cDNA microarray analyses to study the biological processes activated following irradiation with proton beams, both in the non-tumorigenic MCF10A cell line and in two tumorigenic BC cell lines, MCF7 and MDA-MB-231. The immunological signatures were dose dependent in MCF10A and MCF7 cell lines, whereas MDA-MB-231 cells show a strong pro-inflammatory profile regardless of the dose delivered. Clonogenic assay revealed different surviving fractions according to the breast cell lines analyzed. We found the involvement of genes related to cell response to proton irradiation and reported specific cell line- and dose-dependent gene signatures, able to drive cell fate after radiation exposure. Our data could represent a useful tool to better understand the molecular mechanisms elicited by proton irradiation and to predict treatment outcome

Analysis of the role of elution buffers on the separation capabilities of dielectrophoretic devices

Field flow fractionation dielectrophoretic (FFF-DEP) devices are currently used, among the others, for the separation of tumor cells from healthy blood cells. To this end specific suspension/elution buffers (EBs), with reduced conductivity (with respect to that of the cell cytoplasm) are generally used. In this paper we investigate the long-term alterations of the cells and elution buffers. We find that the EB conductivity is critically modified within few minutes after cells suspension. In turn, this modification results in a change the ideal separation frequency of the FFF-DEP device. On the other hand we prove that DEP manipulation is preserved for more than three hours for cells suspended in the considered EBs. Keywords: Dielectrophoresis, Elution buffer, Circulating tumor cells, Cell motilit

Molecular Investigation on a Triple Negative Breast Cancer Xenograft Model Exposed to Proton Beams

Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue

Radiobiological Outcomes, Microdosimetric Evaluations and Monte Carlo Predictions in Eye Proton Therapy

CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) was the first Italian protontherapy facility dedicated to the treatment of ocular neoplastic pathologies. It is in operation at the LNS Laboratories of the Italian Institute for Nuclear Physics (INFN-LNS) and to date, 500 patients have been successfully treated. Even though proton therapy has demonstrated success in clinical settings, there is still a need for more accurate models because they are crucial for the estimation of clinically relevant RBE values. Since RBE can vary depending on several physical and biological parameters, there is a clear need for more experimental data to generate predictions. Establishing a database of cell survival experiments is therefore useful to accurately predict the effects of irradiations on both cancerous and normal tissue. The main aim of this work was to compare RBE values obtained from in-vitro experimental data with predictions made by the LEM II (Local Effect Model), Monte Carlo approaches, and semi-empirical models based on LET experimental measurements. For this purpose, the 92.1 uveal melanoma and ARPE-19 cells derived from normal retinal pigmented epithelium were selected and irradiated in the middle of clinical SOBP of the CATANA proton therapy facility. The remarkable results show the potentiality of using microdosimetric spectrum, Monte Carlo simulations and LEM model to predict not only the RBE but also the survival curves

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

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

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.