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BackgroundProspective data on the natural history of anal human papillomavirus (HPV) infection are scarce in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM).MethodsWe analyzed incidence and clearance of HPV-16 and HPV-18 in a French cohort of HIV-infected MSM, aged ≥35 years, followed-up annually (n = 438, 2014-2018).ResultsHuman papillomavirus-16 and HPV-18 incidence were similar (~10% incident infections at 24 months). Human papillomavirus-16 incidence was higher among high-grade versus no lesion at baseline (adjusted incidence rate ratio = 3.0; 95% confidence interval, 1.07-8.18). Human papillomavirus-16 cleared significantly slower than HPV-18 (32% versus 54% by 24 months).ConclusionsIn conclusion, anal HPV-16 is more persistent than HPV-18, and its incidence correlates with a prior detection of high-grade lesions.

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men living with human immunodeficiency virus and who underwent 3 visits over 2 years, with cytology and high-resolution anoscopy, within the ANRS-EP57-APACHES study. The cumulative HSIL detection rate was 33% (134 of 410), of which 48% HSILs were detected at baseline. HSIL detection varied considerably by center (from 13% to 51%). The strongest HSIL determinants were baseline human papillomavirus 16 (adjusted odds ratio, 8.2; 95% confidence interval, 3.6-18.9) and p16/Ki67 (4.6 [2.3-9.1]). Repeated annual cytology and high-resolution anoscopy improved HSIL detection but did not fully compensate for between-center heterogeneity., Competing Interests: Potential conflicts of interest. O. Z. F. received honoraria from Gilead for a presentation after the 2023 Conference on Retroviruses and Opportunistic Infections, as well as support from ViiV Healthcare for traveling to and attending the European AIDS Conference in October 2023 and the Société Française de Lutte contre le Sida conference in 2022. T. M. D. received grants/contracts from the U.S. National Cancer Institute for the ANCHOR study, central pathology review, and salary support to the University of California, San Francisco. C. J. A.'s employer received an unrestricted research grant from GSK for an investigator-initiated research project not related to this work. I. E. has received payment or honoraria from Merck Sharp & Dohme for an educational event for practitioners. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: The muscle retracting sign (MRS) can be present during endoscopic submucosal dissection (ESD) of macronodular colorectal lesions. The prevalence of MRS and its pathologic and clinical implications is unclear. This study evaluated the effect of MRS on the technical and clinical outcomes of ESD., Methods: All patients referred for ESD of protruding lesions or granular mixed lesions with >10 mm macronodule granular mixed laterally spreading tumors (LST-GMs) in 2 academic centers from January 2017 to October 2022 were prospectively included. Size of the macronodule was analyzed retrospectively. The primary outcome was the curative resection rate according to MRS status. Secondary outcomes were R0 resection, perforation, secondary surgery rate, and risk factors for MRS., Results: Of 694 lesions, 84 (12%) had MRS (MRS+). The curative resection rate was decreased by MRS (MRS+ 41.6% vs lesions without MRS [MRS-] 81.3%), whereas the perforation (MRS+ 22.6% vs MRS- 9.2%), submucosal cancer (MRS+ 34.9% vs MRS- 9.2%), and surgery (MRS+ 45.2% vs MRS- 6%) rates were increased. The R0 resection rate of MRS+ colonic lesions was lower than that of rectal lesions (53% vs 74.3%). In multivariate analysis, protruding lesions (odds ratio, 2.47; 95% confidence interval, 1.27-4.80) and macronodules >4 cm (odds ratio, 4.24; 95% confidence interval, 2.23-8.05) were risk factors for MRS., Conclusions: MRS reduces oncologic outcomes and increases the perforation rate. Consequently, procedures in the colon should be stopped if MRS is detected, and those in the rectum should be continued due to the morbidity of alternative therapy., Competing Interests: Disclosure The following authors disclosed financial relationships: J. Albouys: support for meeting from Amgen; consulting for Boston Scientific; remunerated lecture for Fujifilm; and ESD training for Erbe. M. Schaefer: Consultant for AbbVie; honoraria from Alfasigma, Boston Scientific, Duomed Endoscopy, Erbe Medical, Ferring, and Norgine; and meeting support from Boston Scientific, Cook, Cousin Endoscopy, Erbe, Ipsen, Janssen, Medtronic, Olympus, MSD, and Takeda R. Legros: training event for Pentax Medical, Fujifilm, Erbe, Olympus; and consulting for Boston Scientific. P. Leclercq: speaker fee and advisory board for Medtronic; speaker fee for Erbe; and travel grant from Olympus. M. Dahan: remunerated lecture for MSD; meeting support from Amgen; and training event for Fujifilm. A. Guyot: remunerated lecture for MSD. P. Carrier: consulting for AbbVie; support for meeting from Ipsen; and remunerated lecture for Gilead. V. Loustaud-Ratti: consulting for AbbVie and Gilead; and remunerated lecture for Ipsen. H. Lepetit: remunerated lecture for Fujifilm; and ESD training for Erbe. S. Geyl: remunerated lecture for AbbVie, Galapagos, and Ipsen; and support for meeting from Janssen and Takeda. T. Wallenhorst: training event for Fujifilm and Olympus; and support for meeting from AbbVie. M. Pioche: training event for Olympus, Fujifilm, and Viatris; and educational purposes for Boston Scientific, Olympus, Norgine, and AlfaSigma. J. Jacques: training event for Pentax Medical, Fujifilm, Erbe, and Olympus; and consulting for Boston Scientific. All other authors disclosed no financial relationships., (Copyright © 2024. Published by Elsevier Inc.)

Mismatch repair deficiency (d-MMR)/microsatellite instability (MSI), KRAS , and BRAF mutational status are crucial for treating advanced colorectal cancer patients. Traditional methods like immunohistochemistry or polymerase chain reaction (PCR) can be challenged by artificial intelligence (AI) based on whole slide images (WSI) to predict tumor status. In this systematic review, we evaluated the role of AI in predicting MSI status, KRAS , and BRAF mutations in colorectal cancer. Studies published in PubMed up to June 2023 were included ( n = 17), and we reported the risk of bias and the performance for each study. Some studies were impacted by the reduced number of slides included in the data set and the lack of external validation cohorts. Deep learning models for the d-MMR/MSI status showed a good performance in training cohorts (mean AUC = 0.89, [0.74-0.97]) but slightly less than expected in the validation cohort when available (mean AUC = 0.82, [0.63-0.98]). Contrary to the MSI status, the prediction of KRAS and BRAF mutations was less explored with a less robust methodology. The performance was lower, with a maximum of 0.77 in the training cohort, 0.58 in the validation cohort for KRAS , and 0.82 AUC in the training cohort for BRAF .

This data article provides a dataset of 132421 posts and their corresponding information collected from Twitter social media. The data has two classes, ham or spam, where ham indicates non-spam clean tweets. The main target of this dataset is to study a way to classify whether a post is a spam or not automatically. The data is in Arabic language only, which makes the data essential to the researchers in Arabic natural language processing (NLP) due to the lack of resources in this language. The data is made publicly available to allow researchers to use it as a benchmark for their research in Arabic NLP. The dataset was collected using the Twitter REST API between January 27, 2021, and March 10, 2021. An ad-hoc crawler was constructed using Python programming language to collect the data. Many scientists and researchers will benefit from this dataset in the domain of cybersecurity, NLP, data science and social networking analysis., (© 2023 The Author(s).)

BRCA1 and BRCA2 genes play a crucial role in repairing DNA double-strand breaks through homologous recombination. Their mutations represent a significant proportion of homologous recombination deficiency and are a reliable effective predictor of sensitivity of high-grade ovarian cancer (HGOC) to poly(ADP-ribose) polymerase inhibitors. However, their testing by next-generation sequencing is costly and time-consuming and can be affected by various preanalytical factors. In this study, we present a deep learning classifier for BRCA mutational status prediction from hematoxylin-eosin-safran-stained whole slide images (WSI) of HGOC. We constituted the OvarIA cohort composed of 867 patients with HGOC with known BRCA somatic mutational status from 2 different pathology departments. We first developed a tumor segmentation model according to dynamic sampling and then trained a visual representation encoder with momentum contrastive learning on the predicted tumor tiles. We finally trained a BRCA classifier on more than a million tumor tiles in multiple instance learning with an attention-based mechanism. The tumor segmentation model trained on 8 WSI obtained a dice score of 0.915 and an intersection-over-union score of 0.847 on a test set of 50 WSI, while the BRCA classifier achieved the state-of-the-art area under the receiver operating characteristic curve of 0.739 in 5-fold cross-validation and 0.681 on the testing set. An additional multiscale approach indicates that the relevant information for predicting BRCA mutations is located more in the tumor context than in the cell morphology. Our results suggest that BRCA somatic mutations have a discernible phenotypic effect that could be detected by deep learning and could be used as a prescreening tool in the future., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Our objectives were to better characterize the colorectal function of patients with Spina Bifida (SB). Patients with SB and healthy volunteers (HVs) completed prospectively a standardized questionnaire, clinical evaluation, rectal barostat, colonoscopy with biopsies and faecal collection. The data from 36 adults with SB (age: 38.8 [34.1-47.2]) were compared with those of 16 HVs (age: 39.0 [31.0-46.5]). Compared to HVs, rectal compliance was lower in patients with SB (p = 0.01), whereas rectal tone was higher (p = 0.0015). Ex vivo paracellular permeability was increased in patients with SB (p = 0.0008) and inversely correlated with rectal compliance (r = - 0.563, p = 0.002). The expression of key tight junction proteins and inflammatory markers was comparable between SB and HVs, except for an increase in Claudin-1 immunoreactivity (p = 0.04) in SB compared to HVs. TGFβ1 and GDNF mRNAs were expressed at higher levels in patients with SB (p = 0.02 and p = 0.008). The levels of acetate, propionate and butyrate in faecal samples were reduced (p = 0.04, p = 0.01, and p = 0.02, respectively). Our findings provide evidence that anorectal and epithelial functions are altered in patients with SB. The alterations in these key functions might represent new therapeutic targets, in particular using microbiota-derived approaches.Clinical Trials: NCT02440984 and NCT03054415., (© 2022. The Author(s).)

Background: Hirschsprung-associated enterocolitis physiopathology likely involves disturbed interactions between gut microbes and the host during the early neonatal period. Our objective was to create a neonatal porcine model of iatrogenic aganglionosis to evaluate the impact of the enteric nervous system (ENS) on microbiota and intestinal barrier postnatal development., Methods: Under general anesthesia, the rectosigmoid serosa of 5-day-old suckling piglets was exposed to 0.5% benzalkonium chloride solution (BAC, n = 7) or saline (SHAM, n = 5) for 1 h. After surgery, animals returned to their home-cage with the sow and littermates and were studied 21 days later., Results: BAC treatment induced partial aganglionosis with absence of myenteric plexus and reduced surface area of submucosal plexus ganglia (-58%, P < 0.05) in one third of the rectosigmoid circumference. Epithelial permeability of this zone was increased (conductance +63%, FITC-dextran flux +386%, horseradish-peroxidase flux +563%, P < 0.05). Tight junction protein remodeling was observed with decreased ZO-1 (-95%, P < 0.05) and increased claudin-3 and e-cadherin expressions (+197% and 61%, P < 0.05 and P = 0.06, respectively). BAC piglets harbored greater abundance of proinflammatory bacteria (Bilophila, Fusobacterium) compared to SHAM in the rectosigmoid lumen., Conclusions: This large animal model demonstrates that hypoganglionosis is associated with dramatic defects of gut barrier function and establishment of proinflammatory bacteria., (Copyright © 2020 Elsevier Inc. All rights reserved.)

For patients at high risk of anal cancer, annual screening strategies using invasive evaluation methods are stressful. According to a normal examination at baseline using simple and non invasive tests, the aim of the work was to quantify neoplastic events., Patients and Method: Data from patients with a normal evaluation at the first visit were retrospectively extracted from a prospective database. The individual follow-up period was at least two years and three evaluations. Patients with abnormal cytology were assessed using high-resolution anoscopy and targeted biopsies., Results: A total of 182 subjects (F/M: 10/90, aged 48.1(10.6) years, HIV: 81%) were followed for 41(11) months. Anal cytology remained normal in 94 patients (52%), but high-grade anal neoplasms occurred in 28 patients (15%). Patients with a negative HPV16 status at baseline had cumulative probabilities of high-grade AIN of 0.4%(0.1%-1.9%), 2.6%(1.2%-5.9%) and 7.5%(4.5%-12.2%) after 1 year, 2 years and 3 years of follow-up, respectively. These probabilities were lower than those of patients with a positive HPV16 at baseline and those with a previous history of AIN., Conclusion: In patients with normal cytology and negative HPV16 at baseline, a three-year interval screening may be a less cumbersome alternative to traditional annual screening., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20-30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA -mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management.

Soluble CD95L (s-CD95L) is a chemoattractant for certain lymphocyte subpopulations. We examined whether this ligand is a prognostic marker for high-grade serous ovarian cancer (HGSOC) and whether it is associated with accumulation of immune cells in the tumor. Serum s-CD95L levels in 51 patients with advanced ovarian cancer were tested by ELISA. IHC staining of CD3, CD4, CD8, CD20, CD163, CD31, FoxP3, CCR6, IL-17, Granzyme B, PD-L1, and membrane CD95L was used to assess tumor-infiltrating immune cells. Although the intensity of CD3, CD8, CD4, CD20, and CD163 in tumor tissues remained constant regardless of membrane CD95L expression, tumors in patients with HGSOC with s-CD95L levels ≥516 pg/mL showed increased infiltration by CD3 + T cells ( P = 0.001), comprising both cytotoxic CD8 + ( P = 0.01) and CD4 + ( P = 0.0062) cells including FoxP3 + regulatory T cells ( P = 0.0044). Also, the number of tumor-infiltrating CD20 + B cells ( P = 0.0094) increased in these patients. Multivariate analyses revealed that low s-CD95L concentrations [<516 pg/mL, HR, 3.54; 95% confidence interval (CI), 1.13-11.11), and <1,200 activated CD8 + (Granzyme B + ) cells (HR, 2.63; 95% CI, 1.16-5.95) were independent poor prognostic factors for recurrence, whereas >6,000 CD3 + cells (HR, 0.34; 95% CI, 0.15-0.79) was a good prognostic factor. Thus, low levels of s-CD95L (<516 pg/mL) are correlated with lower numbers of tumor-infiltrating lymphocytes (CD3 + and CD8 + , and also CD4 and FoxP3 T cells) in advanced HGSOC and are a poor prognostic marker. IMPLICATIONS: Serum s-CD95L is correlated with a number of tumor-infiltrating immune cells in HGSOC and could be used as a noninvasive marker of tumor immune infiltration to select patients referred for immunotherapy trials that evaluate checkpoint inhibitor treatment., (©2019 American Association for Cancer Research.)

Study Objective: To develop a predictive score for ovarian malignancy to avoid unnecessary adnexectomy in cases of adnexal mass in pediatric and adolescent girls., Design: A population-based retrospective study on girls who underwent surgery for an ovarian mass with normal levels of human chorionic gonadotrophin and alpha fetoprotein between 1996 and 2016., Setting: Rennes University Hospital, Rennes, France., Participants: Eighty-one patients who received surgery for ovarian tumor., Main Outcome Measures: The main outcome measure was the rate of malignant and borderline tumor. A preoperative scoring system was constructed after multivariate analysis., Results: The rate of malignant ovarian tumor was 6/81 (7%), borderline tumor was 7/81 (9%) (ie, outcome measure: 16%), and benign tumor was 84%. In a univariate analysis, the characteristics significantly associated with malignancy were early puberty, palpable mass, size and content of the tumor, and positive epithelial tumor markers (carcinoma antigen 125, carcinoembryonic antigen, and carcinoma antigen 19-9). The predictive malignancy score was on the basis of 2 variables obtained after multivariate analysis: tumor size and cystic content. The score defined 3 groups at risk for malignancy: low risk, middle-risk, and high-risk. The sensitivity for detecting malignancy was 1.3% (95% confidence interval [CI], 0.1-18.4), 26.2% (95% CI, 11.6-49.0), and 53.1% (95% CI, 29.1-75.8), respectively., Conclusion: We set up a simple predictive score of malignancy on the basis of objective criteria to help decision-making on whether or not ovarian-sparing surgery is feasible in case of children and adolescents with ovarian tumors and normal human chorionic gonadotrophin and alpha fetoprotein levels while ensuring oncologic safety., (Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) recurrent disease and the impact of colposcopic guidance at the time of LLETZ on that risk., Materials and Methods: From December 2013 to July 2014, 204 patients who had undergone LLETZ for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. The use of colposcopy during each procedure was systematically documented. The dimensions and volume of LLETZ specimens were measured at the time of the procedure before formaldehyde fixation. All participants were invited for a follow-up. The primary endpoint was the diagnosis of post-LLETZ recurrent disease defined as the histologic diagnosis of a high-grade cervical intraepithelial lesion., Results: The median duration of post-LLETZ follow-up was 25.8 months. Recurrent disease was diagnosed in 8 (3.6%) patients. Older than 38 years (adjusted hazard ratio [aHR] = 11.9, 95% CI = 1.6-86.0), history of excisional therapy (aHR = 21.6, 95% CI = 3.5-135.3), and the absence of colposcopy for the guidance of LLETZ (aHR = 6.4, 95% CI = 1.1-37.7) were found to significantly increase the risk of post-LLETZ recurrent disease. The dimensions and volume of the specimen were not found to have any impact. Only positive endocervical margins were identified to significantly increase the risk of post-LLETZ recurrent disease (aHR = 14.4, 95% CI = 2.0-101.1)., Conclusions: Risk factors of post-LLETZ recurrent disease are older than 38 years, history of excisional therapy, positive endocervical margins, and lack of colposcopic guidance at the time of LLETZ.

Objective: To assess determinants for histologically proven high-grade anal intraepithelial lesions (hHSIL) in HIV-positive men who have sex with men (MSM), a population at high-risk of HPV-related anal cancer., Design: APACHES is a prospective study of anal HPV and related-lesions in 513 HIV-positive MSM aged at least 35 years in six centres across France., Methods: At baseline, participants underwent high-resolution anoscopy (HRA) with biopsy of suspicious lesions, preceded by anal swabs for liquid-based cytology, p16/Ki67 immunostaining, and HPV DNA. hHSIL diagnosis was established by histopathological review panel consensus, and determinants assessed by logistic regression., Results: Baseline hHSIL prevalence was 10.4% and did not differ significantly by age, sexual behaviour or HIV/immunodeficiency markers. hHSIL prevalence was significantly elevated in participants who smoked (ORadj = 2.6, 95% CI 1.3-5.5) or who, in concurrent anal swabs, had ASCUS/LSIL (3.6, 95% CI 1.4-9.3) or ASC-H/HSIL (22.2, 95% CI 6.8-72.6) cytologic abnormalities, p16/Ki67 dual positivity (3.4, 95% CI 1.5-7.5), or non-HPV16 HR (13.0, 95% CI 1.7-102), but most notably, HPV16 (46.3, 95% CI 6.1-355) infection. Previous diagnosis of low-grade (2.3, 95% CI 1.0-5.4) or high-grade (3.8, 95% CI 1.5-9.9) anal lesion also conveyed higher hHSIL risk. After controlling for patient-specific determinants, there remained significant centre-specific effects, most clearly in higher risk groups (HPV16-positive participants: 31.3% hHSIL in centres A-D versus 5.1% in centres E and F, P < 0.01)., Conclusion: Anal cytology and HPV16 infection are potentially useful determinants of hHSIL risk in HIV-positive MSM, but HIV/immunodeficiency-related variables appear not to be. Controlling for patient-specific hHSIL determinants highlights variability in HRA practice across diverse clinical settings and the need for better standardization of this difficult procedure.

Objective: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) inadequate colposcopy., Materials and Methods: From December 2013 to July 2014, a total of 157 patients who had a LLETZ performed for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. All procedures were performed using semicircular loops. The use of colposcopy made during each procedure was systematically documented. Dimensions and volume of LLETZ specimens were measured at the time of procedure, before formaldehyde fixation. All participants were invited for a follow-up colposcopy 3 to 6 months after LLETZ. Primary end point was the diagnosis of post-LLETZ inadequate colposcopy, defined by a not fully visible cervical squamocolumnar junction and/or cervical stenosis., Results: Colposcopies were performed in a mean (SD) delay of 136 (88) days and were inadequate in 22 (14%) cases. Factors found to significantly increase the probability of post-LLETZ inadequate colposcopy were a history of previous excisional cervical therapy [adjusted odds ratio (aOR) = 4.29, 95% CI = 1.12-16.37, p = .033] and the thickness of the specimen (aOR = 3.12, 95% CI = 1.02-9.60, p = .047). The use of colposcopy for the guidance of LLETZ was statistically associated with a decrease in the risk of post-LLETZ inadequate colposcopy (aOR = 0.19, 95% CI = 0.04-0.80, p = .024) as the achievement of negative endocervical margins (aOR = 0.26, 95% CI = 0.08-0.86, p = .027)., Conclusions: Although the risk of post-LLETZ inadequate colposcopy is increased in patients with history of excisional therapy and with the thickness of the excised specimen, it could be reduced with the use of colposcopic guidance and the achievement of negative endocervical margins.