Sterile inflammation via TRPM8 RNA-dependent TLR3-NF-kB/IRF3 activation promotes antitumor immunity in prostate cancer.

Inflammation is a common condition of prostate tissue, whose impact on carcinogenesis is highly debated. Microbial colonization is a well-documented cause of a small percentage of prostatitis cases, but it remains unclear what underlies the majority of sterile inflammation reported. Here, androgen- independent fluctuations of PSA expression in prostate cells have lead us to identify a prominent function of the Transient Receptor Potential Cation Channel Subfamily M Member 8 (TRPM8) gene in sterile inflammation. Prostate cells secret TRPM8 RNA into extracellular vesicles (EVs), which primes TLR3/NF-kB-mediated inflammatory signaling after EV endocytosis by epithelial cancer cells. Furthermore, prostate cancer xenografts expressing a translation-defective form of TRPM8 RNA contain less collagen type I in the extracellular matrix, significantly more infiltrating NK cells, and larger necrotic areas as compared to control xenografts. These findings imply sustained, androgen-independent expression of TRPM8 constitutes as a promoter of anticancer innate immunity, which may constitute a clinically relevant condition affecting prostate cancer prognosis.

Improved assessment of donor liver steatosis using Banff consensus recommendations and deep learning algorithms.

BACKGROUND & AIMS: The Banff Liver Working Group recently published consensus recommendations for steatosis assessment in donor liver biopsy, but few studies reported their use and no automated deep-learning algorithms based on the proposed criteria have been developed so far. We evaluated Banff recommendations on a large monocentric series of donor liver needle biopsies by comparing pathologists' scores with those generated by convolutional neural networks (CNNs) we specifically developed for automated steatosis assessment. METHODS: We retrospectively retrieved 292 allograft liver needle biopsies collected between January 2016 and January 2020 and performed steatosis assessment using a former intra-institution method (pre-Banff method) and the newly introduced Banff recommendations. Scores provided by pathologists and CNN models were then compared, and the degree of agreement was measured with the intraclass correlation coefficient (ICC). RESULTS: Regarding the pre-Banff method, poor agreement was observed between the pathologist and CNN models for small droplet macrovesicular steatosis (ICC: 0.38), large droplet macrovesicular steatosis (ICC: 0.08), and the final combined score (ICC: 0.16) evaluation, but none of these reached statistically significance. Interestingly, significantly improved agreement was observed using the Banff approach: ICC was 0.93 for the low-power score (p <0.001), 0.89 for the high-power score (p <0.001), and 0.93 for the final score (p <0.001). Comparing the pre-Banff method with the Banff approach on the same biopsy, pathologist and CNN model assessment showed a mean (±SD) percentage of discrepancy of 26.89 (±22.16) and 1.20 (±5.58), respectively. CONCLUSIONS: Our findings support the use of Banff recommendations in daily practice and highlight the need for a granular analysis of their effect on liver transplantation outcomes. IMPACT AND IMPLICATIONS: We developed and validated the first automated deep-learning algorithms for standardized steatosis assessment based on the Banff Liver Working Group consensus recommendations. Our algorithm provides an unbiased automated evaluation of steatosis, which will lay the groundwork for granular analysis of steatosis's short- and long-term effects on organ viability, enabling the identification of clinically relevant steatosis cut-offs for donor organ acceptance. Implementing our algorithm in daily clinical practice will allow for a more efficient and safe allocation of donor organs, improving the post-transplant outcomes of patients.

ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells.

Selection of the best tumor antigen is critical for the therapeutic success of chimeric antigen receptor (CAR) T cells in hematologic malignancies and solid tumors. The anaplastic lymphoma kinase (ALK) receptor is expressed by most neuroblastomas while virtually absent in most normal tissues. ALK is an oncogenic driver in neuroblastoma and ALK inhibitors show promising clinical activity. Here, we describe the development of ALK.CAR-T cells that show potent efficacy in monotherapy against neuroblastoma with high ALK expression without toxicity. For neuroblastoma with low ALK expression, combination with ALK inhibitors specifically potentiates ALK.CAR-T cells but not GD2.CAR-T cells. Mechanistically, ALK inhibitors impair tumor growth and upregulate the expression of ALK, thereby facilitating the activity of ALK.CAR-T cells against neuroblastoma. Thus, while neither ALK inhibitors nor ALK.CAR-T cells will likely be sufficient as monotherapy in neuroblastoma with low ALK density, their combination specifically enhances therapeutic efficacy.

Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

Cohort profile: the Turin prostate cancer prognostication (TPCP) cohort.

Introduction: Prostate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research. Methods: The TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study's prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks. Results: The cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage. Discussion: This study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa.

Impact of operator expertise on transperineal free-hand mpMRI-fusion-targeted biopsies under local anaesthesia for prostate cancer diagnosis: a multicenter prospective learning curve.

PURPOSE: Transperineal mpMRI-targeted fusion prostate biopsies (TPFBx) are recommended for prostate cancer diagnosis, but little is known about their learning curve (LC), especially when performed under local anaesthesia (LA). We investigated how operators' and institutions' experience might affect biopsy results. METHODS: Baseline, procedure and pathology data of consecutive TPFBx under LA were prospectively collected at two academic Institutions, from Sep 2016 to May 2019. Main inclusion criterion was a positive MRI. Endpoints were biopsy duration, clinically significant prostate cancer detection rate on targeted cores (csCDR-T), complications, pain and urinary function. Data were analysed per-centre and per-operator (with ≥ 50 procedures), comparing groups of consecutive patient, and subsequently through regression and CUSUM analyses. Learning curves were plotted using an adjusted lowess smoothing function. RESULTS: We included 1014 patients, with 27.3% csCDR-T and a median duration was 15 min (IQR 12-18). A LC for biopsy duration was detected, with the steeper phase ending after around 50 procedures, in most operators. No reproducible evidence in favour of an impact of experience on csPCa detection was found at operator's level, whilst a possible gentle LC of limited clinical relevance emerged at Institutional level; complications, pain and IPSS variations were not related to operator experience. CONCLUSION: The implementation of TPFBx under LA was feasible, safe and efficient since early phases with a relatively short learning curve for procedure time.

Robot-assisted PSMA-radioguided Surgery to Assess Surgical Margins and Nodal Metastases in Prostate Cancer Patients: Report on Three Cases Using an Intraoperative PET-CT Specimen Imager.

INTRODUCTION: The aim of this feasibility study was to test the intraoperative use of this brand-new specimen PET/CT to guide robot-assisted radical prostatectomy and pelvic lymph node dissection. MATERIALS AND METHODS: Three cases of robot-assisted radical prostatectomy and pelvic lymph node dissection were performed with intraoperative use of the specimen imager. Surgeries were performed with Da Vinci Xi robot. An intravenous injection of 68Ga-PSMA-11 was performed in the OR and after complete excision, the specimens were analyzed with the imager. RESULTS: The average nodal yield was 17.3 (5.8 SD) nodes per patient. Specimen PET/CT images showed a focal uptake in a metastatic node (TBR 13.6), and no uptake or diffuse, faint uptake in negative nodes (TBR range: 1-5.3). The specimen imager provided intraoperative PET/CT images that clearly showed negative surgical margins in two patients, whereas the results were uncertain in a locally advanced case. CONCLUSION: The intraoperative use of the specimen PET/CT imager is safe and feasible and could improve the evaluation of prostate surgical margins and lymph node status.

Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) show potent efficacy in several ALK-driven tumors, but the development of resistance limits their long-term clinical impact. Although resistance mechanisms have been studied extensively in ALK-driven non-small cell lung cancer, they are poorly understood in ALK-driven anaplastic large cell lymphoma (ALCL). Here, we identify a survival pathway supported by the tumor microenvironment that activates phosphatidylinositol 3-kinase γ (PI3K-γ) signaling through the C-C motif chemokine receptor 7 (CCR7). We found increased PI3K signaling in patients and ALCL cell lines resistant to ALK TKIs. PI3Kγ expression was predictive of a lack of response to ALK TKI in patients with ALCL. Expression of CCR7, PI3Kγ, and PI3Kδ were up-regulated during ALK or STAT3 inhibition or degradation and a constitutively active PI3Kγ isoform cooperated with oncogenic ALK to accelerate lymphomagenesis in mice. In a three-dimensional microfluidic chip, endothelial cells that produce the CCR7 ligands CCL19/CCL21 protected ALCL cells from apoptosis induced by crizotinib. The PI3Kγ/δ inhibitor duvelisib potentiated crizotinib activity against ALCL lines and patient-derived xenografts. Furthermore, genetic deletion of CCR7 blocked the central nervous system dissemination and perivascular growth of ALCL in mice treated with crizotinib. Thus, blockade of PI3Kγ or CCR7 signaling together with ALK TKI treatment reduces primary resistance and the survival of persister lymphoma cells in ALCL.

Measuring the Immediate Effects of High-Intensity Functional Training on Motor, Cognitive and Physiological Parameters in Well-Trained Adults.

The importance of physical activity has been widely demonstrated both in clinics and in sports. One of the new frontier training programs is high-intensity functional training (HIFT). The immediate effects of HIFT on the psychomotor and cognitive performance of well-trained people are still not clear. This paper aims to evaluate the immediate effects induced by HIFT on blood lactate levels, physical performance in terms of body stability and jump ability, and cognitive performance in terms of reaction time. Nineteen well-trained participants were enrolled in the experimental studies and asked to execute six repetitions of a circuit training. Data were gathered both in a pre-training session and after each one of the circuit repetitions. An immediate significant increase with respect to the baseline was observed during the first repetition, with a further increase after the third one. No effects on jump ability were found, whereas a deterioration in body stability was found. Positive immediate effects on cognitive performance in terms of accuracy and speed in task execution were assessed. The findings can be exploited by trainers during coaching to optimize the design of training programs.

Topography of Prostate Cancer Recurrence: A Single-centre Analysis of Salvage Radical Prostatectomy Specimens and Implications for Focal Salvage Treatments.

Background: Most prostate cancer (PCa) recurrences after nonsurgical first-line treatment are managed with androgen deprivation therapy (ADT). When local treatment is indicated, salvage focal treatment (FT) may achieve outcomes similar to those after salvage radical prostatectomy (sRP), with lower morbidity. However, descriptions of the topography of PCa recurrence are scarce. Objective: To describe the characteristics and topography of recurrent PCa at sRP. Design setting and participants: We performed a review of the final pathology for consecutive men undergoing sRP at a single centre between 2007 and 2021. Outcome measurements and statistical analysis: Clinical and pathological outcomes and recurrence localisation (standardised map) were recorded. Suitability for salvage FT was evaluated using criteria defined a priori. Results and limitations: We included 41 men who underwent sRP after whole-gland treatment (82.9% primary radiotherapy). Of these, 68.3% had grade group ≥3 and 46.3% had pT3 disease, including nine men (22%) with seminal vesicle involvement >1 cm. The pN+ rate was 29.3%. Surgical margins were positive in 39% (mostly at the apex, 21.9%). PCa was located at <3 mm from the apex in 68% of cases. The segment most frequently involved was the mid-gland (93%). The median prostate and index lesion (IL) volume was 31.4 cm3 (interquartile range [IQR] 23-37) and 2 cm3 (IQR 0.5-6), respectively. A solitary IL was present in 63.4% of cases, while 7.3% had whole-gland PCa involvement. Overall, 56% of the men (n = 23) were deemed suitable for salvage FT (although seven had pN+ disease). The sample size, single-centre retrospective design, and unavailability of magnetic resonance imaging data are the main limitations. Conclusions: According to sRP pathology, radiorecurrent PCa is an aggressive disease, frequently showing extraprostatic extension, positive margins, and apical involvement. The majority of cases still harbour a solitary index lesion and a consistent proportion may be suitable for a gland-preserving strategy. Patient summary: In this report we looked at the location of prostate cancer recurrence within the prostate gland after radiotherapy or ablation, in which energy (such as heat, cold, or laser energy) is used to kill cells. We found that although these recurrences are often high-grade locally advanced disease, around half of cases might be suitable for a gland-preserving salvage treatment.

Reliability of wearable sensors-based parameters for the assessment of knee stability.

Anterior cruciate ligament (ACL) rupture represents one of the most recurrent knee injuries in soccer players. To allow a safe return to sport after ACL reconstruction, standardised and reliable procedures/criteria are needed. In this context, wearable sensors are gaining momentum as they allow obtaining objective information during sport-specific and in-the-field tasks. This paper aims at proposing a sensor-based protocol for the assessment of knee stability and at quantifying its reliability. Seventeen soccer players performed a single leg squat and a cross over hop test. Each participant was equipped with two magnetic-inertial measurement units located on the tibia and foot. Parameters related to the knee stability were obtained from linear acceleration and angular velocity signals. The intraclass correlation coefficient (ICC) and minimum detectable change (MDC) were calculated to evaluate each parameter reliability. The ICC ranged from 0.29 to 0.84 according to the considered parameter. Specifically, angular velocity-based parameters proved to be more reliable than acceleration-based counterparts, particularly in the cross over hop test (average ICC values of 0.46 and 0.63 for acceleration- and angular velocity-based parameters, respectively). An exception was represented, in the single leg squat, by parameters extracted from the acceleration trajectory on the tibial transverse plane (0.60≤ICC≤0.76), which can be considered as promising candidates for ACL injury risk assessment. Overall, greater ICC values were found for the dominant limb, with respect to the non-dominant one (average ICC: 0.64 and 0.53, respectively). Interestingly, this between-limb difference in variability was not always mirrored by LSI results. MDC values provide useful information in the perspective of applying the proposed protocol on athletes with ACL reconstruction. Thus, The outcome of this study sets the basis for the definition of reliable and objective criteria for return to sport clearance after ACL injury.

Prognostic Utility of the Gleason Grading System Revisions and Histopathological Factors Beyond Gleason Grade.

BACKGROUND: The International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognostication remains unclear. OBJECTIVE: To evaluate if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction. PATIENTS AND METHODS: We conducted a case-control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998-2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC). RESULTS: The ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ≥50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS. CONCLUSION: The Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ≥50% cancer further improve PCa death discrimination slightly.

Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma.

The expression of BCL6 in B-cell lymphoma can be deregulated by chromosomal translocations, somatic mutations in the promoter regulatory regions, or reduced proteasome-mediated degradation. FBXO11 was recently identified as a ubiquitin ligase that is involved in the degradation of BCL6, and it is frequently inactivated in lymphoma or other tumors. Here, we show that FBXO11 mutations are found in 23% of patients with Burkitt lymphoma (BL). FBXO11 mutations impaired BCL6 degradation, and the deletion of FBXO11 protein completely stabilized BCL6 levels in human BL cell lines. Conditional deletion of 1 or 2 copies of the FBXO11 gene in mice cooperated with oncogenic MYC and accelerated B-cell lymphoma onset, providing experimental evidence that FBXO11 is a haploinsufficient oncosuppressor in B-cell lymphoma. In wild-type and FBXO11-deficient BL mouse and human cell lines, targeting BCL6 via specific degraders or inhibitors partially impaired lymphoma growth in vitro and in vivo. Inhibition of MYC by the Omomyc mini-protein blocked cell proliferation and increased apoptosis, effects further increased by combined BCL6 targeting. Thus, by validating the functional role of FBXO11 mutations in BL, we further highlight the key role of BCL6 in BL biology and provide evidence that innovative therapeutic approaches, such as BCL6 degraders and direct MYC inhibition, could be exploited as a targeted therapy for BL.

Sensor-Based Indices for the Prediction and Monitoring of Anterior Cruciate Ligament Injury: Reliability Analysis and a Case Study in Basketball.

The possibility of measuring predictive factors to discriminate athletes at higher risk of anterior cruciate ligament (ACL) injury still represents an open research question. We performed an observational study with thirteen female basketball players who performed monopodalic jumps and single-leg squat tests. One of them suffered from an ACL injury after the first test session. Data gathered from twelve participants, who did not suffer from ACL injury, were used for a reliability analysis. Parameters related to leg stability, load absorption capability and leg mobility showed good-to-excellent reliability. Path length, root mean square of the acceleration and leg angle with respect to the vertical axis revealed themselves as possible predictive factors to identify athletes at higher risk. Results confirm that six months after reconstruction represents the correct time for these athletes to return to playing. Furthermore, the training of leg mobility and load absorption capability could allow athletes to reduce the probability of new injuries.

Low Levels of Urinary PSA Better Identify Prostate Cancer Patients.

Serum prostatic specific antigen (PSA) has proven to have limited accuracy in early diagnosis and in making clinical decisions about different therapies for prostate cancer (PCa). This is partially due to the fact that an increase in PSA in the blood is due to the compromised architecture of the prostate, which is only observed in advanced cancer. On the contrary, PSA observed in the urine (uPSA) reflects the quantity produced by the prostate, and therefore can give more information about the presence of disease. We enrolled 574 men scheduled for prostate biopsy at the urology clinic, and levels of uPSA were evaluated. uPSA levels resulted lower among subjects with PCa when compared to patients with negative biopsies. An indirect correlation was observed between uPSA amount and the stage of disease. Loss of expression of PSA appears as a characteristic of prostate cancer development and its evaluation in urine represents an interesting approach for the early detection of the disease and the stratification of patients.

Automated assessment of glomerulosclerosis and tubular atrophy using deep learning.

In kidney transplantations, pathologists evaluate the architecture of both glomeruli, interstitium and tubules to assess the nephron status. An accurate assessment of glomerulosclerosis and tubular atrophy is crucial for determining kidney acceptance, which is currently based on the pathologists' histological evaluations on renal biopsies in addition to clinical data. In this work, we present an automated algorithm, called RENTAG (Robust EvaluatioN of Tubular Atrophy & Glomerulosclerosis), for the segmentation and classification of glomerular and tubular structures in histopathological images. The proposed novel strategy combines the accuracy of a level-set with the semantic segmentation of convolutional neural networks to detect the glomeruli and tubules contours. In the TEST set, our method exhibited excellent performance in both glomeruli (dice score: 0.9529) and tubule (dice score: 0.9174) detection and outperformed all the compared methods. To the best of our knowledge, the RENTAG algorithm is the first fully automated method capable of quantifying glomerulosclerosis and tubular atrophy in digital histological images. The developed software can be employed for the analysis of pre-transplantation biopsies to support the pathologists' diagnostic activity.

A Machine-Learning Approach to Measure the Anterior Cruciate Ligament Injury Risk in Female Basketball Players.

Anterior cruciate ligament (ACL) injury represents one of the main disorders affecting players, especially in contact sports. Even though several approaches based on artificial intelligence have been developed to allow the quantification of ACL injury risk, their applicability in training sessions compared with the clinical scale is still an open question. We proposed a machine-learning approach to accomplish this purpose. Thirty-nine female basketball players were enrolled in the study. Leg stability, leg mobility and capability to absorb the load after jump were evaluated through inertial sensors and optoelectronic bars. The risk level of athletes was computed by the Landing Error Score System (LESS). A comparative analysis among nine classifiers was performed by assessing the accuracy, F1-score and goodness. Five out nine examined classifiers reached optimum performance, with the linear support vector machine achieving an accuracy and F1-score of 96 and 95%, respectively. The feature importance was computed, allowing us to promote the ellipse area, parameters related to the load absorption and the leg mobility as the most useful features for the prediction of anterior cruciate ligament injury risk. In addition, the ellipse area showed a strong correlation with the LESS score. The results open the possibility to use such a methodology for predicting ACL injury.

A hybrid deep learning approach for gland segmentation in prostate histopathological images.

BACKGROUND: In digital pathology, the morphology and architecture of prostate glands have been routinely adopted by pathologists to evaluate the presence of cancer tissue. The manual annotations are operator-dependent, error-prone and time-consuming. The automated segmentation of prostate glands can be very challenging too due to large appearance variation and serious degeneration of these histological structures. METHOD: A new image segmentation method, called RINGS (Rapid IdentificatioN of Glandural Structures), is presented to segment prostate glands in histopathological images. We designed a novel glands segmentation strategy using a multi-channel algorithm that exploits and fuses both traditional and deep learning techniques. Specifically, the proposed approach employs a hybrid segmentation strategy based on stroma detection to accurately detect and delineate the prostate glands contours. RESULTS: Automated results are compared with manual annotations and seven state-of-the-art techniques designed for glands segmentation. Being based on stroma segmentation, no performance degradation is observed when segmenting healthy or pathological structures. Our method is able to delineate the prostate gland of the unknown histopathological image with a dice score of 90.16 % and outperforms all the compared state-of-the-art methods. CONCLUSIONS: To the best of our knowledge, the RINGS algorithm is the first fully automated method capable of maintaining a high sensitivity even in the presence of severe glandular degeneration. The proposed method will help to detect the prostate glands accurately and assist the pathologists to make accurate diagnosis and treatment. The developed model can be used to support prostate cancer diagnosis in polyclinics and community care centres.