Physical Education on the Beach: An Alternative Way to Improve Primary School Children’s Skill- and Health-Related Outcomes during the COVID-19 Pandemic

: The COVID-19 restrictions could preclude children from participating in physical education (PE) interventions. This study aimed to evaluate the efficacy of a PE intervention conducted on the beach on children's skill- and health-related outcomes, as a possible alternative PE intervention that could be also applied during the COVID-19 pandemic. The study involved 106 primary school children, randomly assigned to the traditional indoor (TI) intervention or to the experimental outdoor (EO) intervention. The intervention period lasted 4 months and consisted of two 1-h sessions per week. Intervention was conducted just before the beginning of the COVID-19 pandemic. Children's anthropometric parameters (height, weight, BMI, body fat percentage, and abdominal circumference), fitness parameter (VO2peak), health parameters (resting heart rate, and systolic and diastolic blood pressure), gross motor coordination, and physical activity level were assessed before and after intervention. Both groups significantly improved fitness and motor coordination but worsened some anthropometric parameters (weight, abdominal circumference) after the intervention period. The EO group showed a higher increase of gross motor coordination than the TI group. Results of this study demonstrated that children benefited from a well-structured PE intervention conducted in the natural environment of the beach improving physical fitness and gross motor coordination. Therefore, planning outdoor PE interventions could be an alternative and safe way to encourage and implement physical activity at school during the particular period of COVID-19 pandemic

Preserving privacy in surgical video analysis using a deep learning classifier to identify out-of-body scenes in endoscopic videos

Surgical video analysis facilitates education and research. However, video recordings of endoscopic surgeries can contain privacy-sensitive information, especially if the endoscopic camera is moved out of the body of patients and out-of-body scenes are recorded. Therefore, identification of out-of-body scenes in endoscopic videos is of major importance to preserve the privacy of patients and operating room staff. This study developed and validated a deep learning model for the identification of out-of-body images in endoscopic videos. The model was trained and evaluated on an internal dataset of 12 different types of laparoscopic and robotic surgeries and was externally validated on two independent multicentric test datasets of laparoscopic gastric bypass and cholecystectomy surgeries. Model performance was evaluated compared to human ground truth annotations measuring the receiver operating characteristic area under the curve (ROC AUC). The internal dataset consisting of 356,267 images from 48 videos and the two multicentric test datasets consisting of 54,385 and 58,349 images from 10 and 20 videos, respectively, were annotated. The model identified out-of-body images with 99.97% ROC AUC on the internal test dataset. Mean +/- standard deviation ROC AUC on the multicentric gastric bypass dataset was 99.94 +/- 0.07% and 99.71 +/- 0.40% on the multicentric cholecystectomy dataset, respectively. The model can reliably identify out-of-body images in endoscopic videos and is publicly shared. This facilitates privacy preservation in surgical video analysis

Are there sex differences in physiological parameters and reaction time responses to overload in firefighters?

Male and female firefighters work side-by-side in the same in strenuous and risky conditions. Anthropometrics, physiological, and reaction time (mean of reaction time -MRT-, and errors made -E) parameters of 12 Female and 13 Male firefighters were compared. Effect of overload (step test with and without equipment) on the MRT and E were analyzed on 3 trials (T1 = 1-1s, T2 = 0.5-1s, T3 = 0.5-0.5s), compared with a pre-test condition (basal). T-test between males and females was applied to assess differences (p<0.05) in all parameters. ANOVA with repeated measures and Bonferroni on 3 conditions of step test between males and females was applied in reaction time variables. Between MRT and E, in T1, T2 and T3 trials and the 3 test conditions, ANCOVA models with interactions were used. Differences (p<0.05) in anthropometric, physiological and reaction time data emerged across groups, and on the 3rd trials (T3 vs T1 and T2) in reaction time parameters of each group. ANCOVA showed differences (p<0.001) in E among trials. Post hoc showed significant differences in T1vsT3 and T1vsT2. MRT x trial interaction was extremely significant (P<0.001). Implementing fitness and reaction time exercise programs is important to decrease the injury risk and increase work capacity in firefighters with reference to female workers

Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents

Microtubule-targeting agents (MTAs) are a class of clinically successful anti-cancer drugs. The emergence of multidrug resistance to MTAs imposes the need for developing new MTAs endowed with diverse mechanistic properties. Benzoxazepines were recently identified as a novel class of MTAs. These anticancer agents were thoroughly characterized for their antitumor activity, although, their exact mechanism of action remained elusive. Combining chemical, biochemical, cellular, bioinformatics and structural efforts we developed improved pyrrolonaphthoxazepines antitumor agents and their mode of action at the molecular level was elucidated. Compound 6j, one of the most potent analogues, was confirmed by X-ray as a colchicine-site MTA. A comprehensive structural investigation was performed for a complete elucidation of the structure-activity relationships. Selected pyrrolonaphthoxazepines were evaluated for their effects on cell cycle, apoptosis and differentiation in a variety of cancer cells, including multidrug resistant cell lines. Our results define compound 6j as a potentially useful optimized hit for the development of effective compounds for treating drug-resistant tumors.This work was supported in part by a grant from the Swiss National Science Foundation (31003A_166608; to M.O.S), grant BFU2016-75319-R (AEI/FEDER, EU) from Ministerio de Economia y Competitividad, Blueprint 282510, AIRC-17217. The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by nature - from natural products chemistry to drug discovery” (to M.O.S. and J.F.D.) and the COST Action EPICHEMBIO CM-1406 (to L.A. and G.C.). This work has also received partial funding from the European Union’s Horizon 2020 (EU) research and innovation programme under the Marie Sklodowska-Curie grant agreement No 721906. Finally, this work was partially funded by MIUR-PRIN project n. 2015Y3C5KP (to L.M.)

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 &lt; .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

p66Shc Deficiency in Chronic Lymphocytic Leukemia Promotes Chemokine Receptor Expression Through the ROS-Dependent Inhibition of NF-κB

The microenvironment of lymphoid organs is central to the pathogenesis of chronic lymphocytic leukemia (CLL). Within it, tumor cells find a favourable niche to escape immunosurveillance and acquire pro-survival signals. We have previously reported that a CLL-associated defect in the expression of the pro-apoptotic and pro-oxidant adaptor p66Shc leads to enhanced homing to and accumulation of leukemic cells in the lymphoid microenvironment. The p66Shc deficiency-related impairment in intracellular reactive oxygen species (ROS) production in CLL cells is causally associated to the enhanced expression of the chemokine receptors CCR2, CXCR3 and CCR7, that promote leukemic cell homing to both lymphoid and non-lymphoid organs, suggesting the implication of a ROS-modulated transcription factor(s). Here we show that the activity of the ROS-responsive p65 subunit of the transcription factor NF-κB was hampered in the CLL-derived cell line MEC-1 expressing a NF-κB-luciferase reporter following treatment with H2O2. Similar results were obtained when intracellular ROS were generated by expression of p66Shc, but not of a ROS-defective mutant, in MEC-1 cells. NF-κB activation was associated with increased expression of the chemokine receptors CCR2, CXCR3 and CCR7. Reconstitution of p66Shc in CLL cells normalized intracellular ROS and hampered NF-κB activation, which led to a decrease in the expression of these homing receptors. Our data provide direct evidence that the p66Shc-deficiency-related ROS depletion in CLL cells concurs to NF-κB hyperactivation and homing receptor overexpression, providing a mechanistic basis for the enhanced ability of these cells to accumulate in the pro-survival lymphoid niche

Multicentric validation of EndoDigest: a computer vision platform for video documentation of the critical view of safety in laparoscopic cholecystectomy

Background: A computer vision (CV) platform named EndoDigest was recently developed to facilitate the use of surgical videos. Specifically, EndoDigest automatically&nbsp;provides short video clips&nbsp;to effectively document the critical view of safety (CVS) in laparoscopic cholecystectomy (LC). The aim of the present study is to validate EndoDigest on a multicentric dataset of LC videos. Methods: LC videos from 4 centers were manually annotated with the time of the cystic duct division and an assessment of CVS criteria. Incomplete recordings, bailout procedures and procedures with an intraoperative cholangiogram were excluded. EndoDigest leveraged predictions of deep learning models for workflow analysis in a rule-based inference system designed to estimate the time of the cystic duct division. Performance was assessed by computing the error in estimating the manually annotated time of the cystic duct division. To provide concise video documentation of CVS, EndoDigest extracted video clips showing the 2&nbsp;min preceding and the 30&nbsp;s following the predicted cystic duct division. The relevance of the documentation was evaluated by assessing CVS in automatically extracted 2.5-min-long video clips. Results: 144 of the 174 LC videos from 4 centers were analyzed. EndoDigest located the time of the cystic duct division with a mean error of 124.0 ± 270.6&nbsp;s despite the use of fluorescent cholangiography in 27 procedures and great variations in surgical workflows across centers. The surgical evaluation found that 108 (75.0%) of the automatically extracted short video clips documented CVS effectively. Conclusions: EndoDigest was robust enough to reliably locate the time of the cystic duct division and efficiently video document CVS despite the highly variable workflows. Training specifically on data from each center could improve results; however, this multicentric validation shows the potential for clinical translation of this surgical data science tool to efficiently document surgical safety

Prostate Cancer Biochemical Recurrence Resulted Negative on [⁶⁸Ga]Ga-PSMA-11 but Positive on [¹⁸F]Fluoromethylcholine PET/CT

For prostate cancer (PCa) biochemical recurrence (BCR), the primarily suggested imaging technique by the European Association of Urology (EAU) guidelines is prostate-specific membrane antigen (PSMA) positron emission tomography/computer tomography (PET/CT). Indeed, the increased detection rate of PSMA PET/CT for early BCR has led to a fast and wide acceptance of this novel technology. However, PCa is a very heterogeneous disease, not always easily assessable with the highly specific PSMA PET with around 10% of cases occuring without PSMA expression. In this paper, we present the case of a patient with PCa BCR that resulted negative on [68Ga]Ga-PSMA-11 PET/CT, but positive on [18F]Fluoromethylcholine (Choline) PET/CT

[68Ga]DOTATOC PET/CT Radiomics to Predict the Response in GEP-NETs Undergoing [177Lu]DOTATOC PRRT: The &ldquo;Theragnomics&rdquo; Concept

Despite impressive results, almost 30% of NET do not respond to PRRT and no well-established criteria are suitable to predict response. Therefore, we assessed the predictive value of radiomics [68Ga]DOTATOC PET/CT images pre-PRRT in metastatic GEP NET. We retrospectively analyzed the predictive value of radiomics in 324 SSTR-2-positive lesions from 38 metastatic GEP-NET patients (nine G1, 27 G2, and two G3) who underwent restaging [68Ga]DOTATOC PET/CT before complete PRRT with [177Lu]DOTATOC. Clinical, laboratory, and radiological follow-up data were collected for at least six months after the last cycle. Through LifeX, we extracted 65 PET features for each lesion. Grading, PRRT number of cycles, and cumulative activity, pre- and post-PRRT CgA values were also considered as additional clinical features. [68Ga]DOTATOC PET/CT follow-up with the same scanner for each patient determined the disease status (progression vs. response in terms of stability/reduction/disappearance) for each lesion. All features (PET and clinical) were also correlated with follow-up data in a per-site analysis (liver, lymph nodes, and bone), and for features significantly associated with response, the &Delta;radiomics for each lesion was assessed on follow-up [68Ga]DOTATOC PET/CT performed until nine months post-PRRT. A statistical system based on the point-biserial correlation and logistic regression analysis was used for the reduction and selection of the features. Discriminant analysis was used, instead, to obtain the predictive model using the k-fold strategy to split data into training and validation sets. From the reduction and selection process, HISTO_Skewness and HISTO_Kurtosis were able to predict response with an area under the receiver operating characteristics curve (AUC ROC), sensitivity, and specificity of 0.745, 80.6%, 67.2% and 0.722, 61.2%, 75.9%, respectively. Moreover, a combination of three features (HISTO_Skewness; HISTO_Kurtosis, and Grading) did not improve the AUC significantly with 0.744. SUVmax, however, could not predict the response to PRRT (p = 0.49, AUC 0.523). The presented preliminary &ldquo;theragnomics&rdquo; model proved to be superior to conventional quantitative parameters to predict the response of GEP-NET lesions in patients treated with complete [177Lu]DOTATOC PRRT, regardless of the lesion site