Primary Subtype Research Articles

Etiology, Clinical Spectrum, Epidemiology, New Developments in Diagnosis and Therapeutic Management of Onychomycosis: An Update

Fungal infections are recognized as an important cause of morbidity as well as mortality, especially in the immune-suppressed subjects worldwide. Onychomycosis is a sporadic fungal infection that can affect any part of the nail unit, including the matrix, bed, and plate. It is caused by a wide variety of fungi that include dermatophytes, yeasts, and non-dermatophyte moulds. Dermatophytes are the most common cause of onychomycosis among the numerous fungi. The disease is mainly sporadic and has been recorded in sexes, all age groups, in rural and urban settings, and developing and developed countries. Onychomycosis affects more than 5% of the world's population today. Distal lateral subungual onychomycosis (DLSO), white superficial onychomycosis (WSO), proximal subungual onychomycosis (PSO), endonyx onychomycosis (EO), and candidal onychomycosis are the five primary subtypes of onychomycosis. The condition can manifest itself in a variety of clinical forms, all of which impact the nails on the fingers and legs. Generalized infections involving both hands have been found on occasion. The infection in immunocompromised patient may cause a serious health problem. A plethora of factors, such as nail trauma, occlusive foot wear, and humidity may predispose to fungal nail infections. Clinical diagnosis should be supported with laboratory findings. Direct microscopic demonstration of the fungal agent in the afflicted nail using the potassium hydroxide procedure and isolation of fungi in pure culture on mycological media, such as Sabouraud dextrose agar, dermatophyte test medium, and Pal sunflower seed agar helps to confirm the diagnosis of onychomycosis. The precise morphology of fungal cultures taken from the clinical specimens of patients can be easily investigated in staining solutions, such a PHOL and Narayan. Direct microscopy in potassium hydroxide is still considered the simplest, quickest, and cheapest way to detect fungal agents in nail scrapings. Onychomycosis medications can be applied locally (amorolfine, ciclopirox, efinaconazole, tavaborole) or taken orally (fluconazole, itraconazole, terbinafine). The cure rate is increased when topical and systemic treatments are used together. Depending on the extent of nail involvement, therapy might last from 3 to 6 months or even longer. It is imperative to manage the risk factors. Hygiene is considered the best prevention strategy of onychomycosis.

Abstract GS5-06: InteractPrint predicts clinically meaningful interactions between cancer epithelial cells and immune cells: Lessons from a single-cell breast cancer atlas

Abstract BACKGROUND: While immunotherapy has revolutionized the treatment of many solid tumors, the efficacy of immunotherapy regimens is comparatively lower in breast cancer. Immunotherapy efficacy is often negatively correlated with intratumor heterogeneity. Novel immunotherapy approaches in breast cancer should leverage how cancer epithelial cell heterogeneity affects immune cells in the tumor microenvironment. However, current definitions of cancer epithelial cell heterogeneity in breast cancer have limited resolution. Single cell RNA-seq (scRNA-seq) provides an unprecedented opportunity to further define cancer epithelial cell heterogeneity and identify how heterogeneity influences interactions with immune cells. METHODS: We generated a novel scRNA-seq dataset of 236,363 cells from 119 primary breast tumors biopsied from 88 patients taken from 8 publicly available datasets, currently the largest published scRNA-seq dataset in breast cancer. To define cancer epithelial cell heterogeneity, we performed unsupervised clustering and supervised clustering based on molecular subtype and expression of clinical target genes on all cancer epithelial cells. This identified 11 gene elements (GEs), which reflect key molecular features that vary between cancer epithelial cells. Receptor-ligand pairing analysis allowed us to determine how cells that highly express each GE interact with various immune cells. We developed InteractPrint, a score to predict the predominant tumor-interacting immune cells, based on the GE composition of an individual patient tumor. RESULTS: In our dataset, 17% of samples were HER2+, 41% were HR+, and 42% were TNBC. This dataset was statistically powered to characterize cancer epithelial cell heterogeneity. For each of the 11 GEs, we predicted interactions with immune cells. Experimentally, GEs with predicted NK cell interactions showed sensitivity to NK cell cytotoxicity. In a spatially resolved transcriptomics dataset, GEs with predicted T cell interactions demonstrated colocalization with CD8+ T cells, while those with limited predicted T cell interactions did not. To infer GE-immune interactions at the patient level (GEs define cell-level interactions), we developed InteractPrint. To validate InteractPrint, we assessed the accuracy of the T cell InteractPrint in predicting response to anti-PD-1 therapy. Across two trials and all breast cancer subtypes, T cell InteractPrint demonstrated significant improvement over PD-L1 in predicting response to anti-PD-1 therapy. In an scRNA-seq dataset of samples from patients treated with pembrolizumab, we observed AUC of 85% (p < 0.005) for T cell InteractPrint vs. 61% (p > 0.05) for PD-L1 in predicting response to anti-PD-1 therapy. In patients treated with paclitaxel + pembrolizumab in the I-SPY 2 trial, we observed AUC of 81% (p < 0.00001) for T cell InteractPrint versus 72% (p = 0.001) for PD-L1. CONCLUSIONS: Our results demonstrate considerable cancer epithelial cell heterogeneity across primary breast tumor samples and clinical subtypes. We defined this heterogeneity and leveraged it to predict immune cell interactions within a patient’s tumor. We developed T cell InteractPrint to capture heterogeneous interactions between cancer epithelial cells and CD8+ T cells. T cell InteractPrint is predictive of response to anti-PD-1 immune checkpoint inhibition at higher AUC than PD-L1. This provides a path forward for the interpretation of cancer epithelial cell heterogeneity in a clinically meaningful way. Citation Format: Lily Xu, Kaitlyn Saunders, Hildur Knutsdottir, Kenian Chen, Julia Maues, Christine Hodgdon, Evanthia T. Roussos Torres, Sangeetha Reddy, Lin Xu, Isaac Chan. InteractPrint predicts clinically meaningful interactions between cancer epithelial cells and immune cells: Lessons from a single-cell breast cancer atlas [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS5-06.

Use of prostate cancer subtyping by gene expression to predict response to radiation and chemohormonal therapies.

241 Background: We previously reported on the use of gene expression profiling to characterize four primary subtypes in an analysis of over 100,000 prostate cancer primary tumors. Here we examine these subtypes and response to radiation (RT) after prostatectomy or chemotherapy in addition to androgen deprivation therapy (ADT) in hormone-sensitive metastatic prostate cancer (mHSPC). Methods: We examined a 215-gene prostate subtyping classifier (PSC) which groups luminal and basal gene expression profiles into one of four subtypes; luminal differentiated (LD), luminal proliferating (LP), basal immune (BI) and basal neuroendocrine-like (BN). The log-rank method was used to compare (i) metastasis-free survival between patients who did and did not receive salvage RT in the META855 cohort of localized disease patients treated with radical prostatectomy (n=855) and the (ii) overall survival of patients on the Phase III mHSPC EA3805 CHAARTED trial of ADT or ADT + docetaxel chemotherapy (n=160). Results: After radical prostatectomy, patients with BI tumors derived benefit from RT in terms of metastasis-free survival ( P=9.23e-4) while those with other subtype tumors did not (Each Log-rank P≥0.5). Patients with metastatic disease and LP tumors derived benefit from docetaxel (Log-rank P=0.002) while those with other subtypes tumors did not (Log-rank P=0.2). Conclusions: Basal-luminal subtyping segments tumors by relevant biological processes with potential implications for identifying patients who benefit from salvage radiation post prostatectomy and addition of docetaxel to ADT in mHSPC.

Immunohistochemical (IHC) subtypes of metastatic bladder cancer (mBC) using GATA3 and CK5/6.

557 Background: Genomic analyses have identified that bladder cancers can be divided into distinct molecular subtypes: luminal and basal. IHC markers GATA3 and CK5/6 have demonstrated >80% accuracy in assessing the luminal and basal subtypes of primary bladder tumors and may be easily utilized in clinical practice. Correlation of the primary bladder subtype with that of metastatic sites has not been demonstrated and associations with clinical outcomes are uncertain. Methods: We retrospectively identified patients with mBC who were treated with systemic therapy and had biopsies of either primary bladder or metastatic sites. Patient demographic, metastatic sites, treatment patterns, and clinical outcomes were recorded. Tissue microarrays (TMA) were constructed from primary and/or metastatic tumors. IHC was performed using mouse monoclonal antibodies: GATA-3 (L50-823, Pharmingen, 1:200) and cytokeratin 5/6 (XM26, Thermo Fisher, 1:100). Luminal (GATA3+, CK5/6-), basal (GATA3-, CK5/6+), double positive (GATA3+, CK5/6+) or double negative (GATA3-, CK5/6-) subtyping was applied. Concordance of matched bladder and metastatic pairs was quantified using Cohen’s kappa. Wilcoxon rank-sum tests were used for comparison of continuous and ordinal measures and chi-square tests were performed for comparison of categorical measures. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed. Results: Of 62 specimens, 37 bladder and 16 metastatic sites were interpretable. Four IHC subtype patterns were identified, most were luminal (n=20) followed by double-positive (n=12), basal (n=5), and double-negative (n=5). Of 10 pairs of matched primary tumor and metastatic sites, there was near-perfect subtype concordance between primary and metastatic tumors (κ=0.84; 95% CI:0.58-1.00). No association between sites of metastatic progression and subtype were identified, nor was there any difference in overall survival between the subtypes (p = 0.70). The basal subtype had numerically worse survival compared to the luminal subtype, HR =0.164 (95% CI: 0.02-1.58, p=0.12). Conclusions: IHC subtyping by GATA3 and CK5/6 is feasible in the clinical setting and showed strong correlation between primary and metastatic sites. A larger analysis is planned to further investigate associations with clinical features and outcomes. [Table: see text]

Transcriptomic Analysis Reveals Dysregulation of the Mycobiome and Archaeome and Distinct Oncogenic Characteristics according to Subtype and Gender in Papillary Thyroid Carcinoma.

Papillary Thyroid Carcinoma (PTC) is characterized by unique tumor morphology, treatment response, and patient outcomes according to subtype and gender. While previous studies have implicated the intratumor bacterial microbiome in the incidence and progression of PTC, few studies have investigated the potential role of fungal and archaeal species in oncogenesis. In this study, we aimed to characterize the intratumor mycobiome and archaeometry in PTC with respect to its three primary subtypes: Classical (CPTC), Follicular Variant (FVPTC), and Tall Cell (TCPTC), and also with respect to gender. RNA-sequencing data were downloaded from The Cancer Genome Atlas (TCGA), including 453 primary tumor tissue samples and 54 adjacent solid tissue normal samples. The PathoScope 2.0 framework was used to extract fungal and archaeal microbial read counts from raw RNA-sequencing data. Overall, we found that the intratumor mycobiome and archaeometry share significant similarities in CPTC, FVPTC, and TCPTC, although most dysregulated species in CPTC are underabundant compared to normal. Furthermore, differences between the mycobiome and archaeometry were more significant between males and females, with a disproportionate number of fungal species overabundant in female tumor samples. Additionally, the expression of oncogenic PTC pathways was distinct across CPTC, FVPTC, and TCPTC, indicating that these microbes may uniquely contribute to PTC pathogenesis in each subtype. Furthermore, differences in the expression of these pathways were observed between males and females. Finally, we found a specific panel of fungi to be dysregulated in BRAF V600E-positive tumors. This study demonstrates the potential importance of microbial species to PTC incidence and oncogenesis.

Jak2/STAT6/c-Myc pathway is vital to the pathogenicity of Philadelphia-positive acute lymphoblastic leukemia caused by P190BCR-ABL

BackgroundThe Philadelphia chromosome encodes the BCR-ABL fusion protein, which has two primary subtypes, P210 and P190. P210 and P190 cause Philadelphia-positive chronic myeloid leukemia (Ph+ CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), respectively. The Ph+ ALL is more malignant than Ph+ CML in disease phenotype and progression. This implies the key pathogenic molecules and regulatory mechanisms caused by BCR-ABL in two types of leukemia are different. It is reported that STAT6 was significantly activated only in P190 transformed cells. However, the potential role and the mechanism of STAT6 activation in Ph+ ALL and its activation mechanism by P190 are still unknown.MethodsThe protein and mRNA levels of STAT6, c-Myc, and other molecules were measured by western blot and quantitative real-time PCR. The STAT6 inhibitor AS1517499 was used to specifically inhibit p-STAT6. The effect of p-STAT6 inhibition on Ph+ CML and Ph+ ALL cells was identified by CCK-8 and FCM assay. Dual luciferase reporter and ChIP assay were performed to confirm the direct binding between STAT6 and c-Myc. The impact of STAT6 inhibition on tumor progression was detected in Ph+ CML and Ph+ ALL mouse models.ResultsOur results demonstrated that P210 induced CML-like disease, and P190 caused the more malignant ALL-like disease in mouse models. STAT6 was activated in P190 cell lines but not in P210 cell lines. Inhibition of STAT6 suppressed the malignancy of Ph+ ALL in vitro and in vivo, whereas it had little effect on Ph+ CML. We confirmed that p-STAT6 regulated the transcription of c-Myc, and STAT6 was phosphorylated by p-Jak2 in P190 cell lines, which accounted for the discrepant expression of p-STAT6 in P190 and P210 cell lines. STAT6 inhibition synergized with imatinib in Ph+ ALL cells.ConclusionsOur study suggests that STAT6 activation plays an essential role in the development of Ph+ ALL and may be a potential therapeutic target in Ph+ ALL.-58AP5UCfdMzXqQFXTpZyFVideo abstract

Comparative Study between Gestational and Chronic diabetic women: Incidence, Predictive Factors and Maternal and Fetal complications

Objective: The rate of Diabetes in Egypt has significantly increased, exceeding international rates. The International Diabetes Federation (IDF) listed Egypt among the world's top 10 countries in the number of patients with Diabetes. There are two primary subtypes of Diabetes in pregnancy. One of these is pregestational diabetes mellitus (PGDM), which occurs before a woman becomes pregnant. The second is hyperglycemia, which was first detected during pregnancy and should be classified as DM in pregnancy (DIP) or gestational DM according to WHO guidelines (GDM). DIP is a disease that may be diagnosed if typical DM criteria are reached during screening, while GDM is diagnosed when women satisfy at least one of the criteria during a 100g oral glucose tolerance test, according to current guidelines (OGTT). GDM is a condition that affects pregnant women who develop hyperglycemia but do not have a history of Diabetes. Method: This prospective study was conducted on ninety pregnant females with normal menstrual cycles before pregnancy. Patient’s demographics, urine and blood analysis, HbA1c and OGTT at 24 weeks gestation, as well as ultrasonic screening for early prediction of any congenital malformations were assayed. Results: There was a significant difference in terms of Oral glucose tolerance test at week 24 during fasting, Oral glucose tolerance test at week 24 after one hour, Oral glucose tolerance test at week 24 after two hours, Oral glucose tolerance test at week 24 after three hours using 100 gms glucose; p-value <0.05. Conclusion: The results of this study concluded that mothers with PGDM had worse pregnancy outcomes than those with GDM.

Saline suppression to distinguish the primary aldosteronism subtype: a diagnostic study.

The saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA), while adrenal vein sampling (AVS) is used to subtype PA as unilateral or bilateral. Criteria that can accurately identify those with bilateral PA based on SST results could reduce the need for AVS. We previously demonstrated that a combination of plasma aldosterone concentration (PAC) < 300 pmol L-1 and a reduction in aldosterone-to-renin ratio (ARR) following recumbent SST had high specificity for predicting bilateral PA in an Australian cohort of 92 patients with PA who have undergone AVS. We sought to validate our predictive criteria in larger, independent cohorts of patients with PA. An international, multi-centre cohort study. Data from 55 patients at Monash Health, Victoria, Australia, 106 patients from the First Affiliated Hospital of Chongqing Medical University, China, and 105 patients from Nihon University Itabashi Hospital, Japan were analysed. A combination of PAC <300 pmol L-1 and a reduction in ARR following recumbent SST predicted bilateral PA with specificities of 88.2%, 97.0%, and 100.0% in Australian, Chinese, and Japanese cohorts, respectively. This criterion could allow 22%-38% of patients with PA to bypass AVS and proceed directly to medical treatment. In patients undergoing the recumbent SST, a post-saline PAC <300 pmol L-1 together with a reduction in ARR can predict bilateral PA with high specificity and may allow targeted treatment to be commenced without AVS in up to a third of patients.

Transition of cluster headache phenotype: An interview-based study

Background Cluster headache exists diagnostically in a chronic and episodic variant between which patients can convert. We aimed to describe how many patients change phenotype, elucidate possible factors associated with this transition and identify differences in clinical features between primary and secondary phenotypes.Methods 540 well-defined cluster headache patients according to current ICHD-criteria completed a cross-sectional semi-structured interview.Results Total transition-incidence for the cohort was 20.7%. Conversion from chronic to episodic was reported by 6.3% and transition from episodic to chronic by 14.4% with attack side shift as a possible predictor (p = 0.007). Compared to primary chronic patients, secondary chronic patients had more frequent (60 vs 34 per month, p = 0.0487), but shorter (60 vs 90 minutes, p = 0.041) attacks. Secondary episodic patients experienced shorter remission periods than primary episodic patients (6 vs 11 months, p = 0.010). Treatment response was poor in all groups and only one third had effective prevention.Conclusion Cluster headache is a fluctuating disorder with a fifth of our cohort having experienced at least one phenotype change during course of disease. Apart from attack side shifts, no predictors for transition were identified. Severity differed between primary and secondary subtypes. Overall, there is an urgent need for better understanding of cluster headache.

Abstract C106: Risk of hepatocellular carcinoma among people living with HIV in the United States

Abstract Background: Hepatocellular carcinoma (HCC) is the primary histological subtype of liver cancer, comprising up to 75% of such cases in the U.S. People living with HIV (PLWH) have a higher risk of HCC than the general population. A higher proportion of PLWH are coinfected with hepatitis B (HBV) or hepatitis C virus (HCV) due to shared transmission modalities such as injection drug use. Highly active antiretroviral therapy has improved survival from HIV infection, creating increased opportunities to develop liver cancer due to prolonged hepatic inflammation caused by chronic infection with HBV or HCV. Methods: We used data from the HIV/AIDS Cancer Match (HACM), a population-based HIV and cancer registry linkage in the U.S. We compared HCC risk in PLWH to the general population using standardized incidence ratios (SIRs), standardized by race/ethnicity, age group, HIV transmission risk group, calendar period, and registry. SIRs were estimated by race/ethnicity, age group, HIV transmission risk group, and calendar period. Poisson regression was used to estimate incidence rate ratios (RRs) among PLWH by race/ethnicity, age group, HIV transmission risk group and calendar period. In addition, data from Symphony Health, a Texas based health aggregator of medical claims determined the prevalence of HBV and/or HCV infection among people with HCC. Adjusted odds ratios identified predictors of HBV and HCV infection in PLWH with HCC. Results: There were 1,530 incident HCC cases from 2001–2016 in PLWH during over 4 million person-years of follow up. Compared to the general population, the overall SIR was 2.92 (95% CI 2.75-3.09). The risk of HCC was strongly elevated across all racial/ethnic and age groups. Rates were highest among NH-White PLWH (SIR 3.86; 95% CI 3.48-4.27) PLWH aged 40-49 (SIR 4.81; 95% CI 4.31-5.35) or aged 20-39 (SIR 4.15; 95% CI 2.82-5.89). Among PLWH, HCC risk was similar across racial/ethnic groups but increased with age. Compared to men who had sex with men (MSM), men who injected drugs had almost 4 times the risk of HCC (RR 3.93; 95% CI 3.38-4.55) while female PWID had a 60% increased risk (RR 1.61; 95% CI 1.28-2.01), and men with other or unknown HIV transmission had a 50% increased risk (RR 1.48; 95% CI 1.27-1.73). Between 2001-2004 and 2013-2016, rates of HCC declined 16% (RR 0.84; 95% CI 0.69-1.03). Using Symphony Health data, there were a total of 146 HCC cases, 38 coinfected with HBV, 84 with HCV, and 16 triply infected cases. Compared to MSMs, persons who inject drugs (PWID) had 85% decreased odds of HBV infection (aOR 0.15; 95% CI 0.05-0.50) and 8 times the odds of HCV infection (aOR 8.03; 95% CI 2.61-24.7). Conclusions: Utilizing recently updated population-based linked-surveillance data, we found risk of HCC has declined over time among PLWH, though rates remain significantly elevated compared to the general population, with particularly high risk among people who inject drugs. Prevention and treatment of HBV and HCV are needed to reduce HCC risk in this population. Citation Format: Jennifer K. McGee-Avila, Ilona Argirion, Thomas R. O’Brien, Eric Engels, Marie-Josèphe Horner, Qianlai Luo, Meredith Shiels. Risk of hepatocellular carcinoma among people living with HIV in the United States [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C106.

Brain metastasis screening in the molecular age.

The incidence of brain metastases (BM) amongst cancer patients has been increasing due to improvements in therapeutic options and an increase in overall survival. Molecular characterization of tumors has provided insights into the biology and oncogenic drivers of BM and molecular subtype-based screening. Though there are currently some screening and surveillance guidelines for BM, they remain limited. In this comprehensive review, we review and present epidemiological data on BM, their molecular characterization, and current screening guidelines. The molecular subtypes with the highest BM incidence are epithelial growth factor receptor-mutated non-small cell lung cancer (NSCLC), BRCA1, triple-negative (TN), and HER2+ breast cancers, and BRAF-mutated melanoma. Furthermore, BMs are more likely to present asymptomatically at diagnosis in oncogene-addicted NSCLC and BRAF-mutated melanoma. European screening standards recommend more frequent screening for oncogene-addicted NSCLC patients, and clinical trials are investigating screening for BM in hormone receptor+, HER2+, and TN breast cancers. However, more work is needed to determine optimal screening guidelines for other primary cancer molecular subtypes. With the advent of personalized medicine, molecular characterization of tumors has revolutionized the landscape of cancer treatment and prognostication. Incorporating molecular characterization into BM screening guidelines may allow physicians to better identify patients at high risk for BM development and improve patient outcomes.

Cell of Origin of Brain and Spinal Cord Tumors.

A better understanding of cellular and molecular biology of primary central nervous system (CNS) tumors is a critical step toward the design of innovative treatments. In addition to improving knowledge, identification of the cell of origin in tumors allows for sharp and efficient targeting of specific tumor cells promoting and driving oncogenic processes. The World Health Organization identifies approximately 150 primary brain tumor subtypes with various ontogeny and clinical outcomes. Identification of the cell of origin of each tumor type with its lineage and differentiation level is challenging. In the current chapter, we report the suspected cell of origin of various CNS primary tumors including gliomas, glioneuronal tumors, medulloblastoma, meningioma, atypical teratoid rhabdoid tumor, germinomas, and lymphoma. Most of them have been pinpointed through transgenic mouse models and analysis of molecular signatures of tumors. Identification of the cell or cells of origin in primary brain tumors will undoubtedly open new therapeutic avenues, including the reactivation of differentiation programs for therapeutic perspectives.

Extramammary paget disease of the penoscrotal region.

Extramammary Paget disease is an uncommon slow growing intraepithelial malignant neoplasm. It can be classified into primary and secondary subtypes, with secondary subtype associated with underlying malignancy. Extramammary Paget disease of the penoscrotal region is extremely rare with very limited literature available describing its clinicopathologic characteristics. We present 6 cases of penoscrotal EMPD diagnosed at our academic medical center over a 20 year period. These included 5 cases of scrotal EMPD and 1 case of penile EMPD. The mean age at diagnosis was 68.6 yrs. (Range 61-78 years), One case of scrotal EMPD had history of renal cell carcinoma and prostatic adenocarcinoma, while one other case presented as recurrent EMPD with initial disease in the left groin. EMPD in the glans penis was associated with a history of urothelial carcinoma in the ureter with pagetoid spread. 3 cases had no progression of the disease till recent follow up, 2 were lost to follow up while 1 case rapidly deteriorated resulting in death. This case had bone metastatic and associated peritoneal carcinomatosis. Thus, Extramammary Paget disease of the penoscrotal area is extremely rare, can be primary or associated with visceral malignancies and usually tends to present at an older age. Peritoneal spread and distant metastasis are associated with rapid progression of the disease.

A Radiomics-Based Model for Potentially More Accurate Identification of Subtypes of Breast Cancer Brain Metastases.

Breast cancer brain metastases (BCBM) may involve subtypes that differ from the primary breast cancer lesion. This study aimed to develop a radiomics-based model that utilizes preoperative brain MRI for multiclass classification of BCBM subtypes and to investigate whether the model offers better prediction accuracy than the assumption that primary lesions and their BCBMs would be of the same subtype (non-conversion model) in an external validation set. The training and external validation sets each comprised 51 cases (102 cases total). Four machine learning classifiers combined with three feature selection methods were trained on radiomic features and primary lesion subtypes for prediction of the following four subtypes: 1) hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, 2) HR+/HER2+, 3) HR-/HER2+, and 4) triple-negative. After training, the performance of the radiomics-based model was compared to that of the non-conversion model in an external validation set using accuracy and F1-macro scores. The rate of discrepant subtypes between primary lesions and their respective BCBMs were 25.5% (n=13 of 51) in the training set and 23.5% (n=12 of 51) in the external validation set. In the external validation set, the accuracy and F1-macro score of the radiomics-based model were significantly higher than those of the non-conversion model (0.902 vs. 0.765, p=0.004; 0.861 vs. 0.699, p=0.002). Our radiomics-based model represents an incremental advance in the classification of BCBM subtypes, thereby facilitating a more appropriate personalized therapy.

Optimized Feature Selection and Image Processing Based Machine Learning Technique for Lung Cancer Detection

The primary contributor to lung cancer is an abnormal proliferation of lung cells. Tobacco usage and smoking cigarettes are the primary contributors to the development of lung cancer. The most common forms of lung cancer fall into two distinct types. Non-small-cell lung cancers and small-cell lung cancers are the two primary subtypes of lung cancer. A computed tomography, or CT, scan is an essential diagnostic technique that may determine the kind of cancer a patient has, its stage, the location of any metastases, and the degree to which it has spread to other organs. Other diagnostic tools include biopsies and pathology tests. The creation of algorithms that allow computers to gain information and abilities by seeing and interacting with the world around them is the core emphasis of the field of machine learning. This article demonstrates how to detect lung cancer via the use of machine learning by using improved feature selection and image processing. Image quality may be improved with the help of the CLAHE algorithm. The K Means technique is used in order to segment a picture into its component components. In order to determine which traits are beneficial, the PSO algorithm is utilised. The photos are then categorised using the SVM, ANN, and KNN algorithms respectively. It uses images obtained from a CT scan. When it comes to detecting lung cancer, PSO SVM provides more accurate results.

Comparative analysis of pediatric anxiety measures in clinical sample: evaluation of the PROMIS pediatric anxiety short forms.

Examine the psychometric properties, validity in relation to a legacy measure, and diagnostic accuracy of the PROMIS Anxiety Short Form 2.0 (PROMIS A-SF) Caregiver and Youth Reports in a clinical sample. Participants were 301 youth and caregivers referred to a behavioral health clinic by their pediatrician. Participants and their caregivers completed PROMIS A-SF (youth and caregiver proxy), SCARED (youth and caregiver proxy), and a semi-structured interview. Descriptive, correlational, test-retest reliability, and receiver operating characteristic (ROC) analyses were conducted for both measures. PROMIS A-SF measures were highly correlated with SCARED total scores and the panic subscale. PROMIS A-SF measures had AUCs ranging from .49-.79 for the detection of any of three primary subtypes of anxiety: Generalized Anxiety, Separation Anxiety, and Social Anxiety. Dimensional anxiety subtypes, such as Social Anxiety may not be well detected on the PROMIS youth measure. Use of the PROMIS A-SF as a part of Evidence Based Assessment process is discussed.

Metaplastic Breast Carcinoma (MBC), Primary Squamous Cell Carcinoma Subtype in A 49-Year-Old Woman: A Case Report

Introduction: Metaplastic Breast Carcinoma (MBC) is quite a challenging case because metaplastic breast cancer is one of the rarest subtypes of invasive breast cancer. It is reported that MBC occurs only 0.2 to 1% throughout the world. The metaplastic changes can be squamous cells or other mesenchymal cell types. Clinically, MBC presents as a large palpable mass and may be associated with rapid growth. The size of MBC tends to be larger compared with other types of invasive breast cancer ranging from 1 to more than 10 cm. Although there are several main categories of MBC, some carcinoma can be difficult to classify due to their unusual histologic patterns. This case report study is to provide a clinicopathological overview and approach to MBC.Case Presentation: We reported a 49-year-old woman who suffered from a breast mass that rapidly grew for less than one year. The microscopic findings showed squamous cell carcinoma. While molecular studies revealed triple negative results for hormone receptors although Human Epidermal Growth Factor Receptor 2 (HER2) overexpression was unusual (&lt; 5%). Then, we confirmed with chromogen in situ hybridization (CISH) and there was no gen amplification for HER2. Microscopically, we found ductal carcinoma in situ and this finding supported breast origin.Conclusions: Metaplastic carcinoma did not have any specific and distinctive signs clinically. Metaplastic carcinoma can be monophasic (with only a metaplastic component) or biphasic with two or more components. As treatment options, our patient received conventional chemotherapy. Metaplastic breast cancer is reported to have a lower response rate to conventional adjuvant chemotherapy and worse clinical outcome after chemotherapy than other forms of triple-negative breast cancer.

Vision transformer-based weakly supervised histopathological image analysis of primary brain tumors

Diagnosis of primary brain tumors relies heavily on histopathology. Although various computational pathology methods have been developed for automated diagnosis of primary brain tumors, they usually require neuropathologists' annotation of region of interests or selection of image patches on whole-slide images (WSI). We developed an end-to-end Vision Transformer (ViT)- based deep learning architecture for brain tumor WSI analysis, yielding a highly interpretable deep-learning model, ViT-WSI. Based on the principle of weakly supervised machine learning, ViT-WSI accomplishes the task of major primary brain tumor type and subtype classification. Using a systematic gradient-based attribution analysis procedure, ViT-WSI can discover diagnostic histopathological features for primary brain tumors. Furthermore, we demonstrated that ViT-WSI has high predictive power of inferring the status of three diagnostic glioma molecular markers, IDH1 mutation, p53 mutation, and MGMT methylation, directly from H&E-stained histopathological images, with patient level AUC scores of 0.960, 0.874, and 0.845, respectively.

Efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma

Objective: To evaluate the efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma (HNRMS). Methods: Information from 45 children diagnosed as non-orbital HNRMS and subjected to surgery combined with neoadjuvant chemoradiotherapy in Beijing Children's Hospital affiliated to Capital Medical University from August 2017 to July 2021 was analyzed. The patients included 25 males and 20 females, aged from 1 to 17 years old. The primary tumor site, pathological subtype, clinical stage, risk group, therapeutic regimen, resection range and outcome of all cases were also collected. The survival curves were made using the Kaplan-Meier method and the potential prognostic factors were investigated by Cox regression analysis. Results: Fifteen (33.3%) of 45 children achieved negative surgical margin under complete tumor resection. The postoperative pathological results showed that there were 20 cases of embryonic subtype, 19 cases of alveolar subtype and 6 cases of spindle sclerosis subtype. The postoperative follow-up time ranged from 4 to 71 months, with a median of 26 months. During the follow-up period, 13 children died, among whom brain metastasis was the most common cause of death, accounting for 7/13. The 3-year overall survival rate was 67.6%. Multivariate analysis showed that non-embryonic subtype (HR=6.26, 95%CI: 1.52-25.87, P=0.011) and failure to reach R0 resection (HR=9.37, 95%CI: 1.18-74.34, P=0.034) were independent risk factors affecting overall survival rate. Conclusion: Surgery combined with neoadjuvant chemoradiotherapy can offer a good efficacy for children with non-orbital HNRMS. Non-embryonic subtype and resection without negative operative microscopic margins are independent risk factors for poor prognosis, and brain metastasis is the main cause of death in these children.

Posterior Cortical Atrophy: Primary Occipital Variant

AbstractBackgroundPosterior Cortical Atrophy (PCA) is one of the atypical Alzheimer’s Disease (AD) variants, characterized by predominant visuospatial and visuoperceptual deficits, with dorsal and ventral subtypes recognized clinically and radiographically. A third primary occipital (caudal) variant has been suggested. The objective of this study was to determine its demographics, clinical manifestations, and biomarker findings.MethodFifty‐two PCA patients with positive amyloid PET scans were investigated. Patients underwent neuropsychological assessment, 3T MRI imaging and FDG‐, amyloid‐ and tau‐PET scans. Regional FDG‐PET values were normalized to the pons and represented as z‐scores relative to a control population. Patients were divided into “primary occipital” and “other PCA” subgroups according to FDG‐PET defined criteria, with primary occipital defined as patients in which the z‐scores for occipital subregions were at least one standard deviation lower (i.e., more abnormal) than the z scores in all other brain regions. Global amyloid‐PET, temporoparietal FDG‐PET and temporal tau‐PET regions‐of‐interest (ROI) were calculated. Student’s T test and Fisher’s exact analyses were used to investigate differences in demographics, clinical findings, and imaging biomarkers across the two groups.ResultNine patients were classified as primary occipital; primary occipital patients were older (64.8±6.9 versus 59.3±6.8, p=0.034) and had more years of education (17.7±1.7 versus 15.1±2.6, p=0.007) compared to the other PCA patients. Clinical evaluation revealed worse performance for the primary occipital group on the Ishihara test for color perception (p&lt;0.001), while the other PCA patients performed worse on the Western Aphasia Battery (WAB) praxis scale (p=0.005). Overall neuropsychiatric symptom burden as defined by the NPI‐Q was lower in the primary occipital group (p&lt;0.001). The FDG‐PET meta‐ROI (weighted median uptake in angular gyrus, posterior cingulate, and inferior temporal ROIs, normalized to the pons and vermis) was higher in the primary occipital subtype (p=0.006), but no differences were observed in amyloid and tau‐PET.ConclusionClinical and biomarker findings suggest primary occipital PCA is characterized by an older age at onset, more color perception dysfunction, less severe ideomotor apraxia and less hypometabolism in temporal‐parietal meta‐ROI compared to more established phenotypes.