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Abstract Background Merkel Cell Carcinoma (MCC) is an aggressive skin cancer that is three times deadlier than melanoma. In 2008, it was found that 80% of MCC cases are caused by the genomic integration of a novel polyomavirus, Merkel Cell Polyomavirus (MCPyV), and the expression of its small and truncated large tumor antigens (ST and LT-t, respectively). MCPyV belongs to a family of human polyomaviruses; however, it is the only one with a clear association to cancer. Methods To investigate the role and mechanisms of various polyomavirus tumor antigens in cellular transformation, Rat-2 and 293A cells were transduced with pLENTI MCPyV LT-t, MCPyV ST, TSPyV ST, HPyV7 ST, or empty pLENTI and assessed through multiple transformation assays, and subcellular fractionations. One-way ANOVA tests were used to assess statistical significance. Results Soft agar, proliferation, doubling time, glucose uptake, and serum dependence assays confirmed ST to be the dominant transforming protein of MCPyV. Furthermore, it was found that MCPyV ST is uniquely transforming, as the ST antigens of other non-oncogenic human polyomaviruses such as Trichodysplasia Spinulosa-Associated Polyomavirus (TSPyV) and Human Polyomavirus 7 (HPyV7) were not transforming when similarly assessed. Identification of structural dissimilarities between transforming and non-transforming tumor antigens revealed that the uniquely transforming domain(s) of MCPyV ST are likely located within the structurally dissimilar loops of the MCPyV ST unique region. Of all known MCPyV ST cellular interactors, 62% are exclusively or transiently nuclear, suggesting that MCPyV ST localizes to the nucleus despite the absence of a canonical nuclear localization signal. Indeed, subcellular fractionations confirmed that MCPyV ST could achieve nuclear localization through a currently unknown, regulated mechanism independent of its small size, as HPyV7 and TSPyV ST proteins were incapable of nuclear translocation. Although nuclear localization was found to be important for several transforming properties of MCPyV ST, some properties were also performed by a cytoplasmic sequestered MCPyV ST, suggesting that MCPyV ST may perform different transforming functions in individual subcellular compartments. Conclusions Together, these data further elucidate the unique differences between MCPyV ST and other polyomavirus ST proteins necessary to understand MCPyV as the only known human oncogenic polyomavirus.

Non-Small cell lung cancer (NSCLC) is one of the most dangerous cancers, with 85% of all new lung cancer diagnoses and a 30-55% of recurrence rate after surgery. Thus, an accurate prediction of recurrence risk in NSCLC patients during diagnosis could be essential to drive targeted therapies preventing either overtreatment or undertreatment of cancer patients. The radiomic analysis of CT images has already shown great potential in solving this task; specifically, Convolutional Neural Networks (CNNs) have already been proposed providing good performances. Recently, Vision Transformers (ViTs) have been introduced, reaching comparable and even better performances than traditional CNNs in image classification. The aim of the proposed paper was to compare the performances of different state-of-the-art deep learning algorithms to predict cancer recurrence in NSCLC patients. In this work, using a public database of 144 patients, we implemented a transfer learning approach, involving different Transformers architectures like pre-trained ViTs, pre-trained Pyramid Vision Transformers, and pre-trained Swin Transformers to predict the recurrence of NSCLC patients from CT images, comparing their performances with state-of-the-art CNNs. Although, the best performances in this study are reached via CNNs with AUC, Accuracy, Sensitivity, Specificity, and Precision equal to 0.91, 0.89, 0.85, 0.90, and 0.78, respectively, Transformer architectures reach comparable ones with AUC, Accuracy, Sensitivity, Specificity, and Precision equal to 0.90, 0.86, 0.81, 0.89, and 0.75, respectively. Based on our preliminary experimental results, it appears that Transformers architectures do not add improvements in terms of predictive performance to the addressed problem., (© 2023. The Author(s).)

Aim: To investigate the potential association among Craniopharyngioma (CP), chronotypes and metabolic risk profile., Subjects and Methods: The study population included 28 patients (46.4% males; 42.6 ± 15.8 years) and 28 controls, age, gender and BMI matched (46.4% males; 46.5 ± 12.9 years). In this study sample, we evaluated: anthropometric measurements (waist circumference, WC; BMI), plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure. Morningness-Eveningness was measured with the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ), which included 19 questions about preferred sleep time and daily performance., Results: in both patients and controls grade I obesity was detected in 15 subjects (53.6%), grade II obesity in 13 subjects (46.4%). In the patient group, the mean score of chronotype was 47.8 ± 12.6. In particular, 9 patients (32.1%) exhibited the morning chronotype, 6 (21.4%) the intermediate chronotype and 13 (46.4.%) the evening chronotype. No significant difference was found in gender and age among the chronotype categories. Patients with the evening chronotype had higher blood pressure values and worse metabolic parameters than those with the morning chronotype. In the control group, the mean score of the chronotype was 57.6 ± 9.5. In particular, 16 (57.1%) subjects exhibited the morning chronotype, 10 (35.7%) the intermediate chronotype and only 2 (7.1.%) the evening chronotype. The prevalence of intermediate and evening chronotypes was higher in females than males ( p = 0.021), while males have a higher prevalence of the morning chronotype. Subjects with intermediate and evening chronotypes had worse metabolic parameters than those with the morning chronotype. In patients, the chronotype score was inversely correlated to WC, BMI, SBP, DBP, plasma glucose, total cholesterol, triglycerides, LDL cholesterol and positively correlated with HDL cholesterol. No correlation was found between age and chronotype. In controls, the chronotype score was inversely correlated to WC, BMI, plasma glucose, total cholesterol, LDL cholesterol. No correlation was found among chronotype and age, blood pressure, triglycerides, HDL cholesterol. Considering the whole population of the study (patients and controls), at logistic regression the chronotype score was significantly associated with the presence of CP., Conclusions: for the first time thus far, our study puts the light on the association of the CP with chronotypes and metabolic alterations in this disease, which are the main determinants of the reduced quality of life, higher morbidity and mortality in this setting of patients. This finding suggests that alterations of chronotype might represent an adjunctive risk for CP patients and a possible target for their integrate management.

Objectives: To determine the safety of urological admissions and procedures during the height of the COVID-19 pandemic using "hot" and "cold" sites. The secondary objective is to determine risk factors of contracting COVID-19 within our cohort., Patients and Methods: A retrospective cohort study of all consecutive patients admitted from March 1 to May 31, 2020 at a high-volume tertiary urology department in London, United Kingdom. Elective surgery was carried out at a "cold" site requiring a negative COVID-19 swab 72-hours prior to admission and patients were required to self-isolate for 14-days preoperatively, while all acute admissions were admitted to the "hot" site.Complications related to COVID-19 were presented as percentages. Risk factors for developing COVID-19 infection were determined using multivariate logistic regression analysis., Results: A total of 611 patients, 451 (73.8%) male and 160 (26.2%) female, with a median age of 57 (interquartile range 44-70) were admitted under the urology team; 101 (16.5%) on the "cold" site and 510 (83.5%) on the "hot" site. Procedures were performed in 495 patients of which eight (1.6%) contracted COVID-19 postoperatively with one (0.2%) postoperative mortality due to COVID-19. Overall, COVID-19 was detected in 20 (3.3%) patients with two (0.3%) deaths. Length of stay was associated with contracting COVID-19 in our cohort (OR 1.25, 95% CI 1.13-1.39)., Conclusions: Continuation of urological procedures using "hot" and "cold" sites throughout the COVID-19 pandemic was safe practice, although the risk of COVID-19 remained and is underlined by a postoperative mortality., Competing Interests: The Authors do not declare any conflict of interest. Funding has been provided the department of Life Sciences and Medicine, King’s College London., (© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Growth hormone deficiency (GHD) in adults is due to a reduced growth hormone (GH) secretion by the anterior pituitary gland which leads to a well-known syndrome characterized by decreased cognitive function and quality of life (QoL), decreased bone mineral density (BMD), increased central adiposity with a reduction in lean body mass, decreased exercise tolerance, hyperlipidemia and increased predisposition to atherogenesis. Considering some similar features between aging and GHD, it was thought that the relative GH insufficiency of the elderly person could make an important contribution to the fragility of elderly. GH stimulation tests are able to differentiate GHD in elderly patients (EGHD) from the physiological reduction of GH secretion that occurs with aging. Although there is no evidence that rhGH replacement therapy increases the risk of developing Diabetes Mellitus (DM), reducing insulin sensitivity and inducing cardiac hypertrophy, long-term monitoring is, however, also mandatory in terms of glucose metabolism and cardiovascular measurements. In our experience comparing the impact of seven years of rhGH treatment on metabolic and cardiovascular parameters in GHD patients divided in two groups [adult (AGHD) and elderly (EGHD) GHD patients], effects on body composition are evident especially in AGHD, but not in EGHD patients. The improvements in lipid profile were sustained in all groups of patients, and they had a lower prevalence of dyslipidemia than the general population. The effects on glucose metabolism were conflicting, but approximately unchanged. The risk of DM type 2 is, however, probably increased in obese GHD adults with impaired glucose homeostasis at baseline, but the prevalence of DM in GHD is like that of the general population. The increases in glucose levels, BMI, and SBP in GHD negatively affected the prevalence of Metabolic Syndrome (MS) in the long term, especially in AGHD patients. Our results are in accordance to other long-term studies in which the effects on body composition and lipid profile are prominent., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Scarano, Riccio, Somma, Arianna, Romano, Di Benedetto, de Alteriis, Colao and Di Somma.)

Purpose: Long-term outcomes of anterior cruciate ligament (ACL) reconstruction are good or excellent; however, 0.7%-20% of patients suffer from recurrent instability due to graft failure. The purpose of this paper was to analyse failure aetiology and the possibilities of revision surgical strategies, with a description of our experience. We obtained optimal and good results in most of our patients., Materials and Methods: We retrospectively reviewed 42 patients who underwent revision surgery (43 revisions) due to relapsing instability after ACL reconstruction between 2006 and 2015. We used allografts in 39 cases and autografts in 4 cases., Results: The 85.7% of the patients obtained optimal results (normal knee; group A) and the 7.2% obtained good results (nearly normal knee; group B) according to the International Knee Documentation Committee score. The most frequent failure causes were traumatic events, non-anatomic tunnel placement, and lack of graft incorporation., Conclusions: A correct revision surgery requires accurate patient evaluation and knee imaging. Preoperative planning starts with the identification of the cause of failure of the primary reconstruction. Then, the most suitable procedure should be determined for each case. It is also important to accurately inform the patient of all the complexity of an ACL revision surgery even if it is a procedure with high rates of excellent and good outcomes.

The immunohistochemical localization of beta-endorphin in the normal testis (two patients) and in the pathologic testis (two cases of Sertoli Cell Only Syndrome, two cases of Klinefelter Syndrome, two cases of post-orchitis tubular sclero-hialinosis) was investigated. No beta-endorphin immunostaining was detected in the normal testis, while positive beta-endorphin immunostaining has been observed in pathologic tissues. These results indicate that, as in animals, beta-endorphin is present in human Leydig cells and may play a local role in regulating male reproductive function.