Identifying mesonephric-like adenocarcinoma of the endometrium by combining SOX17 and PAX8 immunohistochemistry.

AIMS: Mesonephric-like adenocarcinoma (MLA) of the endometrium or ovary is a rare but distinct endometrial carcinoma which has a combination of characteristic morphological, immunohistochemical (IHC) and molecular features. SOX17 has been recently identified as a highly sensitive and specific marker for endometrial and ovarian carcinomas. In this study, we aimed to investigate SOX17 expression in MLA together with other IHCs to differentiate MLAs from other endometrial carcinomas. METHODS: Seventeen previously diagnosed endometrial/ovarian MLAs were collected, and multiple IHCs were performed. Additionally, we performed SOX17, PAX8 and ER on tissue microarrays (TMAs) composed of 652 endometrial carcinomas from 2012 to 2015 when MLA diagnostic criteria were not established. RESULTS: All 17 MLAs showed diffuse strong positive PAX8, negative ER and variable TTF1/GATA3 staining. Notably, all MLAs showed negative (n = 10) or focal weak/moderate (n = 7) staining for SOX17, which is more diffuse and stronger than PAX8 in other endometrial carcinoma subtypes. This finding prompted us to screen TMAs with 652 endometrial carcinomas diagnosed before MLA by an approach of combined SOX17 and PAX8 IHCs, and 14 cases with positive PAX8 but negative/focal weak SOX17 were identified. We further studied the 14 cases by examining morphology and performing additional IHCs (TTF1, GATA3, ER and CD10) and would classify seven (50%) of them as MLAs based on morphological features and positive CD10, TTF1 and/or GATA3 staining. CONCLUSION: Our results suggest that a combination of SOX17 and PAX8 IHCs would aid in diagnosing MLA if the results show strong positive PAX8, but negative SOX17.

Bayesian Inference of Hidden Cognitive Performance and Arousal States in Presence of Music.

Goal: Poor arousal management may lead to reduced cognitive performance. Specifying a model and decoder to infer the cognitive arousal and performance contributes to arousal regulation via non-invasive actuators such as music. Methods: We employ a Bayesian filtering approach within an expectation-maximization framework to track the hidden states during the [Formula: see text]-back task in the presence of calming and exciting music. We decode the arousal and performance states from the skin conductance and behavioral signals, respectively. We derive an arousal-performance model based on the Yerkes-Dodson law. We design a performance-based arousal decoder by considering the corresponding performance and skin conductance as the observation. Results: The quantified arousal and performance are presented. The existence of Yerkes-Dodson law can be interpreted from the arousal-performance relationship. Findings display higher matrices of performance within the exciting music. Conclusions: The performance-based arousal decoder has a better agreement with the Yerkes-Dodson law. Our study can be implemented in designing non-invasive closed-loop systems.

Endometrioid Squamous Proliferations of the Endometrium Express Alpha-Methylacyl-CoA Racemase (P504s).

Squamous morular metaplasia is closely associated with endometrioid proliferative lesions such as endometrial intraepithelial neoplasia, whereas endometrioid adenocarcinoma may also demonstrate squamous differentiation (morular or nonmorular). Alpha-methylacyl-CoA racemase (AMACR; P504s) is an immunohistochemistry marker expressed in many tumors, including prostate adenocarcinoma, renal cell carcinoma, and in a subset of gynecologic carcinomas, predominantly of clear cell histology. In small biopsy samples, the distinction between cervical high-grade squamous intraepithelial lesions (HSILs) involving endocervical glands from endometrioid squamous proliferations can be challenging, given their anatomic vicinity and some degree of morphologic overlap. Following the observation of AMACR positivity by immunohistochemistry within squamous morules in an index case, 35 endometrial samples containing squamous morular metaplasia (25) and nonmorular squamous metaplasia (10), and 32 cases of cervical HSIL involving endocervical glands were stained with AMACR. The endometrial cohort consisted of 2 benign anovulatory endometrium, 7 endometrial polyps, 7 endometrial intraepithelial neoplasia, 4 atypical polypoid adenomyomas, and 15 endometrioid adenocarcinomas. Positive cases were scored as diffuse (≥50%) or focal (<50%). AMACR staining was present in 96.7% of endometrial squamous lesions, including 14 (93.3%) of endometrioid carcinomas, and in all cases of endometrial intraepithelial neoplasia, endometrial polyps, atypical polypoid adenomyomas, and anovulatory endometrium with squamous morular metaplasia or nonmorular squamous metaplasia. In comparison, only 2 cases (5.8%) of cervical HSIL demonstrated positivity for AMACR. In conclusion, AMACR can reliably differentiate the cervical versus endometrial origin of squamous lesions in small biopsy specimens.

Artificial Intelligence-Aided Diagnosis of Breast Cancer Lymph Node Metastasis on Histologic Slides in a Digital Workflow.

Identifying lymph node (LN) metastasis in invasive breast carcinoma can be tedious and time-consuming. We investigated an artificial intelligence (AI) algorithm to detect LN metastasis by screening hematoxylin and eosin (H&E) slides in a clinical digital workflow. The study included 2 sentinel LN (SLN) cohorts (a validation cohort with 234 SLNs and a consensus cohort with 102 SLNs) and 1 nonsentinel LN cohort (258 LNs enriched with lobular carcinoma and postneoadjuvant therapy cases). All H&E slides were scanned into whole slide images in a clinical digital workflow, and whole slide images were automatically batch-analyzed using the Visiopharm Integrator System (VIS) metastasis AI algorithm. For the SLN validation cohort, the VIS metastasis AI algorithm detected all 46 metastases, including 19 macrometastases, 26 micrometastases, and 1 with isolated tumor cells with a sensitivity of 100%, specificity of 41.5%, positive predictive value of 29.5%, and negative predictive value (NPV) of 100%. The false positivity was caused by histiocytes (52.7%), crushed lymphocytes (18.2%), and others (29.1%), which were readily recognized during pathologists' reviews. For the SLN consensus cohort, 3 pathologists examined all VIS AI annotated H&E slides and cytokeratin immunohistochemistry slides with similar average concordance rates (99% for both modalities). However, the average time consumed by pathologists using VIS AI annotated slides was significantly less than using immunohistochemistry slides (0.6 vs 1.0 minutes, P = .0377). For the nonsentinel LN cohort, the AI algorithm detected all 81 metastases, including 23 from lobular carcinoma and 31 from postneoadjuvant chemotherapy cases, with a sensitivity of 100%, specificity of 78.5%, positive predictive value of 68.1%, and NPV of 100%. The VIS AI algorithm showed perfect sensitivity and NPV in detecting LN metastasis and less time consumed, suggesting its potential utility as a screening modality in routine clinical digital pathology workflow to improve efficiency.

DSCC_Net: Multi-Classification Deep Learning Models for Diagnosing of Skin Cancer Using Dermoscopic Images.

Skin cancer is one of the most lethal kinds of human illness. In the present state of the health care system, skin cancer identification is a time-consuming procedure and if it is not diagnosed initially then it can be threatening to human life. To attain a high prospect of complete recovery, early detection of skin cancer is crucial. In the last several years, the application of deep learning (DL) algorithms for the detection of skin cancer has grown in popularity. Based on a DL model, this work intended to build a multi-classification technique for diagnosing skin cancers such as melanoma (MEL), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanocytic nevi (MN). In this paper, we have proposed a novel model, a deep learning-based skin cancer classification network (DSCC_Net) that is based on a convolutional neural network (CNN), and evaluated it on three publicly available benchmark datasets (i.e., ISIC 2020, HAM10000, and DermIS). For the skin cancer diagnosis, the classification performance of the proposed DSCC_Net model is compared with six baseline deep networks, including ResNet-152, Vgg-16, Vgg-19, Inception-V3, EfficientNet-B0, and MobileNet. In addition, we used SMOTE Tomek to handle the minority classes issue that exists in this dataset. The proposed DSCC_Net obtained a 99.43% AUC, along with a 94.17%, accuracy, a recall of 93.76%, a precision of 94.28%, and an F1-score of 93.93% in categorizing the four distinct types of skin cancer diseases. The rates of accuracy for ResNet-152, Vgg-19, MobileNet, Vgg-16, EfficientNet-B0, and Inception-V3 are 89.32%, 91.68%, 92.51%, 91.12%, 89.46% and 91.82%, respectively. The results showed that our proposed DSCC_Net model performs better as compared to baseline models, thus offering significant support to dermatologists and health experts to diagnose skin cancer.

Comparison of intralesional 5-fluorouracil and intralesional triamcinolone acetonide in the treatment of localized vitiligo.

The objective of this study was to compare the efficacy and safety of intralesional 5-fluorouracil (5-FU) and triamcinolone acetonide (TA) in the treatment of localized vitiligo. the A non-randomized control trial conducted at Sheikh Zayed Hospital, RYK, from January to June 2022 included sixty patients, aged 18-60 years, with stable vitiligo. Patients were divided into two groups: Group A received 5-FU and Group B received TA. The outcome was assessed using the Vitiligo Area Scoring Index (VASI). There were 58.3% male and 41.7% female, with an average age of 33.33±11.24 years. Baseline characteristics between the two treatment groups were comparable. At 12 weeks, treatment responses were classified as excellent (16.6%), good (16.6%), moderate (35%) and poor (31.6%), with no significant intergroup differences (p=0.203). The 5-FU group showed a more significant lesion size reduction (1.28±1.09cm²) than the TA group (0.61±1.21 cm²) (p=0.028). Adverse effects mainly included pain and erythema. Common side effects included pain and erythema. The study concludes that both intralesional 5-FU and TA are effective and safe for treating localized vitiligo, with 5-FU potentially being more efficacious in lesion size reduction and promoting repigmentation.

Alkyl Silica Hybrid Nanowire Assembly in Improved Superhydrophobic Membranes for RO Filtration.

Alkyl silica membranes and wires were synthesized by a sol-gel method, which has the capacity to control the size of the particles or membranes by controlling the reactions. Trimethoxyoctylsilane (C8TMOS) was used as a chemical surfactant; poly(vinylpyrrolidone) (PVP) as an emulsifier, dissolved in butanol for emulsion; and tetraethylorthosilicate (TEOS) as a precursor and a source of silica. An assembly of silica wires was fabricated on glass and cotton substrates by the dip-coating technique. Porous membranes and silica wires were observed using scanning electron microscopy (SEM) images. The contact angles of all of the samples were in the range of 140-154° as measured by ImageJ software, which confirmed the hydrophobic nature of the samples. The contact angle was increased by increasing the amount of the surfactant. Phase changes of silica wires and membranes were investigated by thermogravimetric analysis. Chemical bonds of the sample were studied using Fourier transform infrared (FTIR) spectroscopy. The band gap of silica nanowires was measured to be 3.8-3.4 eV using the UV-visible spectrum and decreased as compared to that of bulk silica. These silica-based porous membranes with enhanced transport properties can be used in filtration and separation techniques. This fabricated hybrid silica membrane showed ∼96% salt rejection within a permeation flux of 3.04 L/m2 h.

A State-space Investigation of Impact of Music on Cognitive Performance during a Working Memory Experiment.

Stress has effects on productivity and performance. Poor stress management may lead to reduced productivity and performance. Non-invasive actuators such as music have the potential to effectively regulate stress. In this study, using a state-space approach, we obtain a performance state to investigate the performance during a working memory task while playing two different types of music in the background. In our experiments, participants performed a working memory task while listening to calming and vexing music of their choice. We utilize the binary correct/incorrect response and the continuous reaction time of the response from the participants to quantify the performance. The state-space quantification reveals that vexing music has a statistically significant positive impact on the obtained performance state. This indicates the feasibility of designing non-invasive closed-loop systems to regulate stress for maximizing performance and productivity.

Patient and Public Involvement for Dementia Research in Low- and Middle-Income Countries: Developing Capacity and Capability in South Asia.

Background: Patient and public involvement (PPI) is an active partnership between the public and researchers in the research process. In dementia research, PPI ensures that the perspectives of the person with "lived experience" of dementia are considered. To date, in many lower- and middle-income countries (LMIC), where dementia research is still developing, PPI is not well-known nor regularly undertaken. Thus, here, we describe PPI activities undertaken in seven research sites across South Asia as exemplars of introducing PPI into dementia research for the first time. Objective: Through a range of PPI exemplar activities, our objectives were to: (1) inform the feasibility of a dementia-related study; and (2) develop capacity and capability for PPI for dementia research in South Asia. Methods: Our approach had two parts. Part 1 involved co-developing new PPI groups at seven clinical research sites in India, Pakistan and Bangladesh to undertake different PPI activities. Mapping onto different "rings" of the Wellcome Trust's "Public Engagement Onion" model. The PPI activities included planning for public engagement events, consultation on the study protocol and conduct, the adaptation of a study screening checklist, development and delivery of dementia training for professionals, and a dementia training programme for public contributors. Part 2 involved an online survey with local researchers to gain insight on their experience of applying PPI in dementia research. Results: Overall, capacity and capability to include PPI in dementia research was significantly enhanced across the sites. Researchers reported that engaging in PPI activities had enhanced their understanding of dementia research and increased the meaningfulness of the work. Moreover, each site reported their own PPI activity-related outcomes, including: (1) changes in attitudes and behavior to dementia and research involvement; (2) best methods to inform participants about the dementia study; (3) increased opportunities to share knowledge and study outcomes; and (4) adaptations to the study protocol through co-production. Conclusions: Introducing PPI for dementia research in LMIC settings, using a range of activity types is important for meaningful and impactful dementia research. To our knowledge, this is the first example of PPI for dementia research in South Asia.

A Cytosolic Multiprotein Complex Containing p85α Is Required for ß-Catenin Activation in Colitis and Colitis-associated Cancer.

Wnt/ß-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated ß-catenin (pß-Cat(Ser-552)) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in ß-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with ß-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85(ΔIEC)) mice develop more severe dextran sodium sulfate colitis due to delayed ulcer healing and reduced epithelial ß-catenin activation. In colonic IEC, p85α deficiency did not alter PI3K signaling. In vitro shRNA depletion of individual complex members disrupts the MCC and reduces ß-catenin signaling. Despite worse colitis, p85(ΔIEC) mice have reduced tumor burden after azoxymethane/dextran sodium sulfate treatment. Together the data indicate that the ß-catenin MCC is needed for mucosal repair and carcinogenesis. This novel MCC may be an attractive therapeutic target in preventing cancer in colitis patients.