Artificial intelligence and high-resolution anoscopy: automatic identification of anal squamous cell carcinoma precursors using a convolutional neural network.

BACKGROUND: High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell cancer (ASCC) precursors. Although it is superior to other diagnostic methods, particularly cytology, the visual identification of areas suspected of having high-grade squamous intraepithelial lesions remains difficult. Convolutional neural networks (CNNs) have shown great potential for assessing endoscopic images. The aim of the present study was to develop a CNN-based system for automatic detection and differentiation of HSIL versus LSIL in HRA images. METHODS: A CNN was developed based on 78 HRA exams from a total of 71 patients who underwent HRA at a single high-volume center (GH Paris Saint-Joseph, Paris, France) between January 2021 and January 2022. A total of 5026 images were included, 1517 images containing HSIL and 3509 LSIL. A training dataset comprising 90% of the total pool of images was defined for the development of the network. The performance of the CNN was evaluated using an independent testing dataset comprising the remaining 10%. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve (AUC) were calculated. RESULTS: The algorithm was optimized for the automatic detection of HSIL and its differentiation from LSIL. Our model had an overall accuracy of 90.3%. The CNN had sensitivity, specificity, positive and negative predictive values of 91.4%, 89.7%, 80.9%, and 95.6%, respectively. The area under the curve was 0.97. CONCLUSIONS: The CNN architecture for application to HRA accurately detected precursors of squamous anal cancer. Further development and implementation of these tools in clinical practice may significantly modify the management of these patients.

A critical test of twelve methods for estimating age using radiographic staging of developing teeth on a sample of 6- to 15-year-old children from Mérida, Yucatán (México).

Cross-population applicability of osteological and dental methods is a known issue in forensic anthropology, but very little is known about whether differences between populations are due to ancestry, environment effects, or even the statistical approach utilized for developing the methods. This study wishes to add to the discussion of population-specificity of dental age estimation methods and examine the impact of their statistical basis on their accuracy and precision. These parameters were estimated by testing 12 different dental age estimation techniques on a sample of 182 panoramic radiographs of children between the ages of 6 and 15 years (110 girls and 72 boys) from the city of Mérida in Yucatán, México. None of the 12 methods selected is based on Mexican samples. Dental maturation was scored following and methods tested employed two dental scoring schemes: Moorrees, Fanning, and Hunt's (MFH) 13-/14-stage system and Demirjian's 8-stage system. Results show that methods derived from more geographically specific groups do not fare better or worse than methods developed on more diverse and inclusive international samples, even if no methods specific to Mexicans were tested. While some of the methods performed very well, and they were not based on a Mexican sample, this suggests that population-specific dental age estimation methods may be relatively unimportant or that population differences in dental maturation are very small. Other issues seemed to have a greater impact on accuracy and precision, such as age dependency, inclusion of the third molar in age assessments, age truncation and age heaping in reference samples, the dental scoring scheme used, and how predicted age is calculated mathematically. As such, findings in this study suggest that validation tests of age estimation methods may not be a useful or reliable means to assess population differences and that these differences need to be more systematically assessed if an argument is to be made for the increased accuracy and precision of population-specific methods. The statistical basis of dental prediction methods seems to have a more significant role in their accuracy and precision outside of their reference sample.

Artificial intelligence and colon capsule endoscopy: development of an automated diagnostic system of protruding lesions in colon capsule endoscopy.

BACKGROUND: Colon capsule endoscopy (CCE) is a minimally invasive alternative for patients unwilling to undergo conventional colonoscopy, or for whom the latter exam is contraindicated. This is particularly important in the setting of colorectal cancer screening. Nevertheless, these exams produce large numbers of images, and reading them is a monotonous and time-consuming task, with the risk of overlooking important lesions. The development of automated tools based on artificial intelligence (AI) technology may improve some of the drawbacks of this diagnostic instrument. METHODS: A database of CCE images was used for development of a Convolutional Neural Network (CNN) model. This database included anonymized images of patients with protruding lesions in the colon or patients with normal colonic mucosa or with other pathologic findings. A total of 3,387,259 frames from 24 CCE exams were retrospectively reviewed. For CNN development, 3640 images (860 protruding lesions and 2780 with normal mucosa or other findings) were ultimately extracted. Training and validation datasets were constructed for the development and testing of the CNN. RESULTS: The CNN detected protruding lesions with a sensitivity, specificity, positive and negative predictive values of 90.7, 92.6, 79.2 and 96.9%, respectively. The area under the receiver operating characteristic curve for detection of protruding lesions was 0.97. CONCLUSIONS: The deep learning algorithm we developed is capable of accurately detecting protruding lesions. The application of AI technology to CCE may increase its diagnostic accuracy and acceptance for screening of colorectal neoplasia.

Liver transplant recipients have a higher prevalence of anal squamous intraepithelial lesions.

BACKGROUND: Anal squamous intraepithelial lesions (ASIL) are precancerous lesions of anal squamous cell carcinoma, with a higher prevalence in immunosuppressed patients. There are some studies in kidney transplant recipients, but there is no information regarding prevalence in liver transplantation. Our aim was to evaluate the prevalence of ASIL in this setting. METHODS: Prospective case-control study involving liver transplant recipients without any other known risk factor for ASIL (n=59), which were compared with a healthy control group (n=57). All were submitted to anal cytology and high-resolution anoscopy was performed in those with abnormal results. RESULTS: Ten (17%) of liver transplant recipients had abnormal cytological results, seven patients had atypical squamous cells of undetermined significance (ASC-US), one patient had atypical squamous cells that cannot exclude high-grade (ASC-H) and two patients had high-grade squamous intraepithelial lesions (HSIL). In the control group, one patient (2%) had an ASC-US result (P=0.005). Anal squamous intraepithelial lesions were confirmed in 7 out of 10 of liver transplant patients and 0 out of 1 in the controls (P=0.013) by high-resolution anoscopy with biopsies. Current smoking was the only risk factor for abnormal cytology (odds ratio=5.87, 95% confidence intervals=1.22-28.12, P=0.027). CONCLUSIONS: Liver transplant patients have a higher risk of ASIL. Screening should be considered, especially in smokers.

Examining the socioeconomic effects on third molar maturation in a Portuguese sample of children, adolescents and young adults.

INTRODUCTION: The impact of socioeconomic status (SES) on tooth mineralization has seldom been evaluated. This is important because SES can be used as a proxy for quantifying factors in the environmental that can impact mineralization but that can be difficult to measure directly, such as nutrition. OBJECTIVE: The objective of this study was to examine the effects of SES on third molar mineralization, using a sample of children, adolescents and young adults from Porto, Portugal. METHODS: Panoramic x-rays from 1747 patients (842 males and 904 females) were used in this study. Eight hundred and fifteen individuals were patients attending a private practice and were classified as high SES (384 males and 458 females), whereas the remaining 932 subjects (458 males and 474 females) were patients attending the dental clinic at the Faculty of Dental Medicine, University of Porto and were classified as low SES. Inclusion of individuals on the each SES group was also based on parental and own occupation. The mandibular third molar was assessed for its maturation using Demirjian's stages. The median age of attainment of root stages was calculated for stages D to H, using logistic regression and compared between the high and low SES samples. RESULTS: Boys from the higher SES group show an earlier median age of attainment for stages D, E, and F. Girls from the higher SES group also show an earlier median age of attainment, but for stages D and E. Stages G and H did not show SES differences in both sexes. CONCLUSIONS: Patients from the higher SES group showed a consistent advancement in maturation of the third molar, although SES differences diminish and eventually disappear in the last stages of root maturation. An accelerated effect related to overweight and obesity is suggested as the primary explanation.

Age estimation of immature human skeletal remains using the post-natal development of the occipital bone.

Whenever age cannot be estimated from dental formation in immature human skeletal remains, other methods are required. In the post-natal period, development of the skeleton provides alternative age indicators, namely, those associated with skeletal maturity of the cranium. This study wishes to document the age at which the various ossification centres in the occipital bone fuse and provide readily available developmental probabilistic information for use in age estimation. A sample of 64 identified immature skeletons between birth and 8 years of age from the Lisbon collection was used (females = 29, males = 35). Results show that fusion occurs first in the posterior intra-occipital synchondrosis and between the jugular and condylar limbs of the lateral occipital to form the hypoglossal canal (1-4 years), followed by the anterior intra-occipital (3-7 years). Fusion of the post-natal occipital does not show differences in timing between males and females. Relative to other published sources, this study documents first and last ages of fusion of several ossification centres and the posterior probabilities of age given a certain stage of fusion. Given the least amount of overlap in stages of fusion, the closure of the hypoglossal canal provides the narrowest estimated age with the highest probability of age.

Peri-operative management of a patient with an ectodermal dysplasia (Rapp-Hodgkin) syndrome.

We present the case of a 41-year-old man with Rapp-Hodgkin syndrome who underwent nasal septum deviation surgery under general anaesthesia. This syndrome is rare, with approximately 70 cases reported worldwide. It is one of a group of ectodermal dysplasia syndromes and results from the aberrant development of ectoderm during fetal development. Some of the clinical features may affect anaesthetic management. The most important considerations are potentially difficult airway management, the need for meticulous temperature control, and the importance of skin protection. This case was uneventful, but as there are few case reports on the management of patients with ectodermal dysplasia syndromes undergoing anaesthesia this report contributes useful knowledge. The pathogenesis and clinical features of Rapp-Hodgkin syndrome and the anaesthetic management for this patient are described.

Involvement of alternative oxidase (AOX) in adventitious rooting of Olea europaea L. microshoots is linked to adaptive phenylpropanoid and lignin metabolism.

UNLABELLED: Alternative oxidase (AOX) has been proposed as a functional marker candidate in a number of events involving cell differentiation, including rooting efficiency in semi-hardwood shoot cuttings of olive (Olea europaea L.). To ascertain the general importance of AOX in olive rooting, the auxin-induced rooting process was studied in an in vitro system for microshoot propagation. Inhibition of AOX by salicylhydroxamic acid (SHAM) significantly reduced rooting efficiency. However, the inhibitor failed to exhibit any effect on the preceding calli stage. This makes the system appropriate for distinguishing dedifferentiation and de novo differentiation during root induction. Metabolite analyses of microshoots showed that total phenolics, total flavonoids and lignin contents were significantly reduced upon SHAM treatment. It was concluded that the influence of alternative respiration on root formation was associated to adaptive phenylpropanoid and lignin metabolism. Transcript profiles of two olive AOX genes (OeAOX1a and OeAOX2) were examined during the process of auxin-induced root induction. Both genes displayed stable transcript accumulation in semi-quantitative RT-PCR analysis during all experimental stages. In contrary, when the reverse primer for OeAOX2 was designed from the 3'-UTR instead of the ORF, differential transcript accumulation was observed suggesting posttranscriptional regulation of OeAOX2 during metabolic acclimation. This result confirms former observations in olive semi-hardwood shoot cuttings on differential OeAOX2 expression during root induction. It further points to the importance of future studies on the functional role of sequence and length polymorphisms in the 3'-UTR of this gene. KEY MESSAGE: The manuscript reports the general importance of AOX in olive adventitious rooting and the association of alternative respiration to adaptive phenylpropanoid and lignin metabolism.

Subarachnoid and subdural haematoma after attempted spinal anaesthesia for caesarean section.

We report a case of a previously healthy patient who developed a vertebral canal haematoma in the subarachnoid and subdural spaces after a spinal puncture for elective caesarean section. Vertebral canal haematomas are rare. There are different mechanisms for haematoma formation, but coagulation disturbances and trauma, most often due to needle punctures, are the most important. Vertebral canal haematoma may warrant emergent surgical decompression. In this case report we discuss vertebral canal haematomas, including possible mechanisms, clinical diagnosis, imaging modalities, methods for management and advice for patients. We consider the possible association between a vertebral canal haematoma and non-steroidal anti-inflammatory drugs, and draw attention to an existing black box warning for ketorolac. In this case, we explain why a conservative approach was chosen with a good outcome. We also report the effect of this complication on the patient experience.

Environmental effects on skeletal versus dental development II: further testing of a basic assumption in human osteological research.

This study further tests the general assumption that skeletal development is more sensitive to socioeconomic factors than dental development in a sample of modern immature Portuguese skeletons (N = 41) of known sex, age, and socioeconomic background. Skeletal development was assessed from skeletal maturation of the knee and dental development was assessed from schedules of tooth formation. Discrepancies between physiological age (skeletal and dental age) and chronological age were used as a measure of developmental status. A positive score indicates that physiological age is in advance of chronological age, whereas a negative score indicates the reverse. Two socioeconomic groups, one of low and the other of high socioeconomic status, were created based on the occupation of the father and on the place of residence, and developmental status was compared between the two socioeconomic groups. Results confirm previous studies by showing that dental development is less affected by environmental insults than skeletal maturation. While socioeconomic differences in skeletal maturation range from 1.20 to 1.22 years (15-18% of chronological age), socioeconomic differences in dental maturation range from 0.51 to 0.53 years (4-9% of chronological age). Compared to a previous study, results also suggest that skeletal maturation is more affected than skeletal growth. Additionally, an adaptation of the radiographic atlas of skeletal development of the knee is proposed for use with dry skeletal material.

Synovial entrapment in alloplastic temporomandibular joint replacement.

Complications of alloplastic temporomandibular joint (TMJ) prostheses can lead to stress and anxiety for the patient and the surgical team, and prosthesis substitution is sometimes required. The aim of this case report is to describe the surgical finding of synovial entrapment with interposed fibrosis in a postoperative alloplastic TMJ revision, managed effectively with adequate surgical debridement. The authors believe that synovial entrapment needs to be considered as a possible postoperative complication of total joint replacement when no clear symptoms of infection, metal hypersensitivity, osteolysis, or heterotopic bone formation are present. The implications of synovial entrapment in TMJ alloplastic replacement remains relatively unpredictable and poorly understood.

Role of enteroscopy in the diagnosis of whipple's disease.

Whipple's disease is a rare chronic systemic infection caused by Tropheryma whipplei. The widespread infection by this rod is responsible for the protean clinical manifestations of the disease, although its classical form is notable for the prevalence of abdominal symptoms such as chronic diarrhea and abdominal pain. Whitish-yellow patches, suggestive of lymphangiectasia, are typically observed in the duodenum during upper endoscopy. The diagnosis of this condition is supported by the identification in duodenal biopsies of Periodic acid-Schiff staining within lamina propria macrophages. Nevertheless, a significant portion of patients do not have lesions within the range of conventional upper endoscopy. Therefore, other endoscopic procedures such as video capsule endoscopy and enteroscopy may be useful to detect more distal lesions. The authors describe a case where the combined used of both techniques allowed the unmasking of this disease.

Establishing a minimum postmortem interval of human remains in an advanced state of skeletonization using the growth rate of bryophytes and plant roots.

This paper illustrates the usefulness and efficiency of botanical evidence in establishing a minimum postmortem interval (PMI). The case under analysis refers to the remains of an adult male in an advanced state of skeletonization recovered from a wooded area in northern Portugal. The skeleton showed several taphonomical changes, which included the presence of green algae, bryophytes, and growing shrub roots in, around, and through the remains. By determining the age of both the bryophytes and shrub roots, it was concluded that the minimum amount of time elapsed since death was 3 years, to which several months or a few years have to be added to account for the complete decomposition of the remains. The disappearance of the presumptive individual had occurred 6 years before and is fully consistent with the estimate of the PMI. This report illustrates a novel use of bryophytes in a forensic setting.

Prevalence of vitamin D receptor gene polymorphism in a Uruguayan population and its relation to type 1 diabetes mellitus.

Vitamin D has important immuno-modulatory properties and it influences insulin secretion. It acts through a vitamin D receptor (VDR), for which several gene polymorphisms have been described. The Uruguayan population presents several epidemiological characteristics that make it different from that of other counties, including other Latin-American countries. It went through miscegenation processes, with a tri-hybrid European, Amerindian and African origin, with no contribution from isolated Amerindian communities. Such differences have important consequences for the relationship between frequencies of several genes in the general population and their association with the diabetes mellitus. We examined the prevalence of VDR gene polymorphisms in the general population and their relation to type 1 diabetes in a parent-case design. One hundred unrelated individuals from the general population and 45 parent-patient triads with a child affected with type 1 diabetes were genotyped for FokI, BsmI and TaqI VDR gene polymorphisms by RFLP-PCR. We used a transmission disequilibrium test to assess preferential transmission of parents to affected offspring. The prevalence of the three VDR polymorphisms was: allele F = 48%, B = 35%, T = 64%. The f, b, T alleles and heterozygous genotypes were found at a high frequency in this population. Among 36 informative heterozygous parental genotypes, 30 transmitted the F allele (probability of transmission = 83%). The other two polymorphisms did not show significant transmission. We suggest that FokI polymorphism indicates susceptibility to type 1 diabetes mellitus in the Uruguayan population.

In vitro mutagenicity of anti-inflammatory parsalmide analogues PA7, PA10, and PA31 triggered by biotransformation into hydroxy derivatives.

In this study, the mutagenicity of the anti-inflammatory parsalmide [5-amino-N-butyl-2-(2-propynyloxy)-benzamide] analogues PA7 [5-amino-N-butyl-2-cyclohexyloxy-benzamide], PA10 [5-amino-N-butyl-2-phenoxy-benzamide] and PA31 [5-amino-N-butyl-2-(p-tolyloxy)-benzamide] was determined by an Ames Salmonella assay. The experiments were performed by preincubating the compounds in the absence and presence of a post-mitochondrial fraction (S9) of rat liver homogenate from phenobarbital/beta-naphtoflavone treated rats. No mutagenic effect was observed after direct testing (no S9 added) in Salmonella typhymurium strains TA98, TA100, TA102, TA1535 and TA1537. However, in the presence of S9, the test substances triggered mutagenic responses in strains TA100 and TA98. PA31 presented the strongest mutagenic potential. The reversion rates in the presence of PA31 were about 2-19 fold higher than spontaneous mutation rates. In the presence of PA7, the reversion increased 2-14-fold over spontaneous rates. While PA10 showed a relatively mild mutagenic potential, as the number of revertants did not exceed 2.5 times the number of spontaneous mutations. Mass spectrometric analysis of the in vitro biotransformation showed that S9 converted (%), regioselectively, PA7 (19%), PA10 (7%) and PA31 (12%) into hydroxy-derivatives.

The Emerging Role of Regucalcin as a Tumor Suppressor: Facts and Views.

Regucalcin (RGN) is a multifunctional protein that was first described as a calcium (Ca2+)-binding protein playing a relevant role in the maintenance of intracellular Ca2+ concentration. However, due to its downregulated expression with aging, RGN is also known as senescence marker protein-30. The RGN protein is an X-chromosome gene product, whose transcription is regulated by a myriad of hormonal and non-hormonal factors. Besides the well-known role in Ca2+ homeostasis, RGN has also been linked to the control of several intracellular signaling pathways, and basic biological processes, such as oxidative stress, cell proliferation, apoptosis, and metabolism. RGN has been shown to have antioxidant properties by its activity reducing the production of reactive oxygen species and increasing the antioxidant defenses. The role of RGN suppressing cell proliferation is associated with the regulation of expression of oncogenes and tumor suppressor genes. It results clear that all the existent knowledge implicates RGN in the control of the main biological processes actually recognized as the hallmarks of cancer. Moreover, it has been shown that tumor onset and progression are underpinned by the loss of RGN expression, whereas RGN overexpression showed to have a protective role against the development of chemicallyinduced tumors. This review describes the mechanisms that control the tissue expression of RGN and discusses the experimental evidence that indicate RGN as a new tumor suppressor protein.