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Diffuse spinal cord gliomas (SCGs) are rare tumors associated with a high morbidity and mortality that affect both pediatric and adult populations. In this retrospective study, we sought to characterize the clinical, pathological, and molecular features of diffuse SCG in 22 patients with histological and molecular analyses. The median age of our cohort was 23.64 years (range 1–82) and the overall median survival was 397 days. K27M mutation was significantly more prevalent in males compared to females. Gross total resection and chemotherapy were associated with improved survival, compared to biopsy and no chemotherapy. While there was no association between tumor grade, K27M status (p = 0.366) or radiation (p = 0.772), and survival, males showed a trend toward shorter survival. K27M mutant tumors showed increased chromosomal instability and a distinct DNA methylation signature.

Introduction:Limited research has examined the experience and psychosocial effect of vision impairment in older adults. We examine the relationship between vision impairment and stigma using guided interviews among older adults with age-related eye disease. Methods:Thirty-six participants with vision impairment were recruited from glaucoma (n= 18) (better eye visual fields mean deviations: >5 and <15 decibels) or retina (n= 18) (better eye visual acuity: <20/40 and >20/400) clinics of the Johns Hopkins Wilmer Eye Institute between 2015 and 2020. Participants completed interviews to examine stigma surrounding age-related vision impairment. Interviews were transcribed and analyzed using directed content analysis. Results:Content analyses of interview transcripts revealed underlying stigma within our cohort. Starting with categories of (1) interpersonal relationships and (2) evolving self-perception, specific domains of stigma were realized in this study. Although both enacted (external) stigma and perceived stigma were acknowledged by a subset of participants, few endorsed internalized stigma. In the face of stigma, participants demonstrated notable resiliency in adapting to and living with age-related vision impairment, captured in an additional category of (3) behavioral adaptations. Discussion:In-depth interviews revealed that older adults with vision impairment confront specific domains of stigma, including enacted and perceived stigma. Features protective against internalized stigma included older age, community support, and assistive technologies. Implications for Practitioners:A recognition of the subtypes of stigma that older adults with age-related vision impairment face is necessary to tailor support and target interventions.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed as nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of obesity and metabolic syndrome. It is mainly caused by insulin resistance. With the increased risk of visceral obesity in South Asians, the prevalence of MASLD is on the rise. The morbidity associated with MASLD and its complications, including hepatocellular carcinoma is projected to increase in this South Asian population.

Diabetic retinopathy is one of the most threatening complications of diabetes that leads to permanent blindness if left untreated. Severity of the diabetic retinopathy disease is based on presence of microaneurysms, exudates, neovascularisation and haemorrhages. Convolutional neural networks have been successfully applied in many adjacent subjects, and for diagnosis of diabetic retinopathy itself. In this paper, an automatic deep-learning-based method for stage detection of diabetic retinopathy by single photography of the human fundus is proposed. Additionally, the multistage approach to transfer learning, which makes use of similar datasets with different labelling, is experimented. The proposed architecture gives high accuracy in classification through spatial analysis. Amongst other supervised algorithms involved, proposed solution is to find a better and optimized way to classifying the fundus image with little pre-processing techniques. The proposed architecture deployed with dropout layer techniques yields 78 percent accuracy.

Uterine perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that occasionally shares morphologic and immunohistochemical overlap with low- and high-grade endometrial stromal sarcoma (LGESS and HGESS). In this study, we sought to characterize the clinical, morphologic, genetic, and epigenetic features of five uterine sarcomas that display histologic features of LGESS, HGESS, and PEComa. All tumors demonstrated epithelioid cells often associated with a low-grade spindled component resembling LGESS, with both regions expressing CD10, ER, PR, variable HMB45, and Melan-A immunoreactivity, and strong cathepsin K and pS6 expression. Targeted massively parallel sequencing analysis revealed the presence of somatic TSC2mutations in all five cases, of which four harbored concurrent or consecutive JAZF1-SUZ12gene fusions. Unsupervised hierarchical clustering analysis of methylation profiles of TSC2-mutant uterine sarcomas (n= 4), LGESS (n= 10), and HGESS (n= 12) demonstrated two clusters consisting of (1) all LGESS and TSC2-mutant uterine sarcomas and (2) all HGESS. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, calcium, and Rap1 signaling. TSC2-mutant uterine sarcomas were responsive to hormone suppression, and mTOR inhibition demonstrated clinical benefit in four patients with these neoplasms. Our results suggest that these tumors represent histologically distinctive LGESS with TSC2mutations. TSC2mutations and JAZF1-SUZ12fusion may help diagnose these tumors and possibly direct effective treatment.

Supplemental Digital Content is Available in the Text.

COVID 19 pandemic is causing a global health epidemic. The most powerful safety tool is wearing a face mask in public places and everywhere else. The COVID 19 outbreak forced governments around the world to implement lockdowns to deter virus transmission. According to survey reports, wearing a face mask at public places reduces the risk of transmission significantly. In this paper, an IoT-enabled smart door that uses a machine learning model for monitoring body temperature and face mask detection. The proposed model can be used for any shopping mall, hotel, apartment entrance, etc. As an outcome a cost-effective and reliable method of using AI and sensors to build a healthy environment. Evaluation of the proposed framework is done by the Face Mask Detection algorithm using the TensorFlow software library. Besides, the body temperature of the individual is monitored using a non-contact temperature sensor. This proposed system can detect the users from COVID 19 by enabling the Internet of Things (IoT) technology.

Industrial effluent discharge threatens both agricultural productivity and drinking water quality by depleting groundwater, contaminating surface water and demanding high-quality irrigation water. This study evaluates the influence of urbanization and agricultural activities on the groundwater quality in Perundurai, focusing on its suitability for both drinking and agriculture. A total fourty samples of groundwater were randomly taken from bore wells. The principal cations and anions were analyzed revealed their dominance order: Na Ca > Mg > K and Cl > SO4 > F > NO3. The water quality index (WQI) analysis found that around 89% samples are unsuitable for drinking. The PI value indicates that 2% samples have poor permeability and elevated risk of waterlogging make it unsuitable for field use. Analysis of the Piper diagram reveals the dominance of alkaline earth cations (Ca, Mg) over alkali metals (Na, K) and weak acids (HCO3, CO3) over strong acids (Cl, SO4), indicating specific hydrogeochemical facies. From the US salinity diagram (USSL), C4S1 samples (30%) exhibit low alkalinity but a hazardous high salinity which impairs their capacity to retain water. Wilcox classification identified that 27% samples exhibit potential limitations for irrigation due to elevated sodium content. Contamination of groundwater due to ion leaching, sewage discharge and runoff is a significant environmental concern with potential health implications.

Epilepsy is a heterogenous group of disorders defined by recurrent seizure activity due to abnormal synchronized activity of neurons. A growing number of epilepsy cases are believed to be caused by genetic factors and copy number variants (CNV) contribute to up to 5% of epilepsy cases. However, CNVs in epilepsy are usually large deletions or duplications involving multiple neurodevelopmental genes. In patients who underwent seizure focus resection for treatment-resistant epilepsy, whole genome DNA methylation profiling identified 3 main clusters of which one showed strong association with receptor tyrosine kinase (RTK) genes. We identified focal copy number gains involving epidermal growth factor receptor (EGFR) and PDGFRAloci. The dysplastic neurons of cases with amplifications showed marked overexpression of EGFR and PDGFRA, while glial and endothelial cells were negative. Targeted sequencing of regulatory regions and DNA methylation analysis revealed that only enhancer regions of EGFRand gene promoter of PDGFRAwere amplified, while coding regions did not show copy number abnormalities or somatic mutations. Somatic focal copy number gains of noncoding regulatory represent a previously unrecognized genetic driver in epilepsy and a mechanism of abnormal activation of RTK genes. Upregulated RTKs provide a potential avenue for therapy in seizure disorders.

Uterine perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that occasionally shares morphologic and immunohistochemical overlap with low- and high-grade endometrial stromal sarcoma (LGESS and HGESS). In this study, we sought to characterize the clinical, morphologic, genetic, and epigenetic features of five uterine sarcomas that display histologic features of LGESS, HGESS, and PEComa. All tumors demonstrated epithelioid cells often associated with a low-grade spindled component resembling LGESS, with both regions expressing CD10, ER, PR, variable HMB45, and Melan-A immunoreactivity, and strong cathepsin K and pS6 expression. Targeted massively parallel sequencing analysis revealed the presence of somatic TSC2mutations in all five cases, of which four harbored concurrent or consecutive JAZF1-SUZ12gene fusions. Unsupervised hierarchical clustering analysis of methylation profiles of TSC2-mutant uterine sarcomas (n= 4), LGESS (n= 10), and HGESS (n= 12) demonstrated two clusters consisting of (1) all LGESS and TSC2-mutant uterine sarcomas and (2) all HGESS. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, calcium, and Rap1 signaling. TSC2-mutant uterine sarcomas were responsive to hormone suppression, and mTOR inhibition demonstrated clinical benefit in four patients with these neoplasms. Our results suggest that these tumors represent histologically distinctive LGESS with TSC2mutations. TSC2mutations and JAZF1-SUZ12fusion may help diagnose these tumors and possibly direct effective treatment.

IMPORTANCE: Preventive care is associated with decreased morbidity and mortality among older adults. Vision impairment may be a barrier to accessing care and health promotion information and therefore may contribute to decreased preventive care uptake. OBJECTIVE: To examine the association between self-reported vision impairment and uptake of preventive care services (ie, breast and colon cancer screenings and influenza and pneumococcal vaccinations). DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study using the 2015 and 2018 National Health Interview Survey (NHIS) and 2016 and 2018 Behavioral Risk Factor Surveillance System (BRFSS) data, national surveys of US residents conducted through in-person household interviews in NHIS, and state-based telephone interviews in BRFSS. Participants included respondents 50 years and older based on eligibility for each preventive care service examined. EXPOSURES: Vision impairment, defined as self-reported trouble seeing, in NHIS, and self-reported blindness/serious difficulty seeing in BRFSS. MAIN OUTCOMES AND MEASURES: Self-reported uptake of breast cancer screening (women aged 50-74 years), colon cancer screening (aged 50-74 years), influenza vaccination (50 years and older), and pneumococcal vaccination (65 years and older). Multivariable regression models adjusted for relevant confounders, including age, were used to examine the uptake of each preventive care service by vision impairment status. RESULTS: Among NHIS participants, older US individuals with vision impairment (prevalence between 14.3% and 16.3% in the different age groups; n = 12 120-29 654) were less likely to report breast cancer screening (odds ratio [OR], 0.82; 95% CI, 0.71-0.96) and colon cancer screening (OR, 0.89; 95% CI, 0.79-0.99) but not influenza (OR, 1.06; 95% CI, 0.97-1.15) and pneumococcal vaccination (OR, 1.03; 95% CI, 0.91-1.16), as compared with their counterparts without vision impairment. In BRFSS (n = 228 649-530 027), those with vision impairment (5.9%-6.8%) were less likely than those without vision impairment to report breast cancer screening (OR, 0.67; 95% CI, 0.59-0.75), colon cancer screening (OR, 0.70; 95% CI, 0.65-0.76), and pneumococcal vaccination (OR, 0.89; 95% CI, 0.81-0.99) but not influenza vaccination (OR, 0.95; 95% CI, 0.89-1.00). CONCLUSIONS AND RELEVANCE: Older Americans with vision impairment may be less likely to use cancer-related preventive services as compared with their counterparts without vision impairments. These findings suggest that interventions to improve access to health information and health care services for individuals with vision impairment may be needed to improve cancer screening among this population.

Pleomorphic xanthoastrocytoma (PXA) is a rare type of brain tumor that affects children and young adults. Molecular prognostic markers of PXAs remain poorly established. Similar to gangliogliomas, PXAs show prominent immune cell infiltrate, but its composition also remains unknown. In this study, we correlated DNA methylation and BRAF status with clinical outcome and explored the tumor microenvironment. We performed DNA methylation in 21 tumor samples from 18 subjects with a histological diagnosis of PXA. MethylCIBERSORT was used to deconvolute the PXA microenvironment by analyzing the associated immune cell-types. Median age at diagnosis was 16 years (range 7-32). At median follow-up of 30 months, 3-year and 5-year overall survival was 73% and 71%, respectively. Overall survival ranged from 1 to 139 months. Eleven out of 18 subjects (61%) showed disease progression. Progression-free survival ranged from 1 to 89 months. Trisomy 7 and CDKN2A/B (p16) homozygous deletion did not show any association with overall survival (p = 0.67 and p = 0.74, respectively). Decreased overall survival was observed for subjects with tumors lacking the BRAF V600E mutation (p = 0.02). PXAs had significantly increased CD8 T-cell epigenetic signatures compared with previously profiled gangliogliomas (p = 0.0019). The characterization of immune cell-types in PXAs may have implications for future development of immunotherapy.

Congenital tumors account for 2% to 4% of all pediatric central nervous system tumors. Glioblastoma multiforme (GBM) represents a small subset of these tumors. Despite harboring histologic features similar to older patients, infants with GBM exhibit improved survival and respond more favorably to surgery and chemotherapy. To highlight this tumor’s unique behavior, we report the case of a survivor of infantile GBM who developed a recurrent tumor in the surgical bed 6 months after diagnosis. The tumor was ultimately resected and was a ganglioglioma. This case shows both a favorable clinical outcome to an infantile GBM and this tumor’s natural history.

ROS1 is a transmembrane receptor tyrosine kinase proto-oncogene that has been shown to have rearrangements with several genes in glioblastoma and other neoplasms, including intrachromosomal fusion with GOPC due to microdeletions at 6q22.1. ROS1 fusion events are important findings in these tumors, as they are potentially targetable alterations with newer tyrosine kinase inhibitors; however, whether these tumors represent a distinct entity remains unknown. In this report, we identify 3 cases of unusual pediatric glioma with GOPC-ROS1 fusion. We reviewed the clinical history, radiologic and histologic features, performed methylation analysis, whole genome copy number profiling, and next generation sequencing analysis for the detection of oncogenic mutation and fusion events to fully characterize the genetic and epigenetic alterations present in these tumors. Two of 3 tumors showed pilocytic features with focal expression of synaptophysin staining and variable high-grade histologic features; the third tumor aligned best with glioblastoma and showed no evidence of neuronal differentiation. Copy number profiling revealed chromosome 6q22 microdeletions corresponding to the GOPC-ROS1 fusion in all 3 cases and methylation profiling showed that the tumors did not cluster together as a single entity or within known methylation classes by t-Distributed Stochastic Neighbor Embedding.

Graphical abstract

To find the prevalence of Ceftazidime-Avibactam (CAZ-AVI) resistant Klebsiella pneumoniaein clinical isolates and to determine the genes responsible for Ceftazidime-Avibactam resistance using PCR.

Supplemental Digital Content is available in the text.Meningiomas are a central nervous system tumor primarily afflicting adults, with <1% of cases diagnosed during childhood or adolescence. Somatic variation in NF2may be found in ∼50% of meningiomas, with other genetic drivers (eg, SMO, AKT1, TRAF7) contributing to NF2wild-type tumors. NF2is an upstream negative regulator of YAP signaling and loss of the NF2protein product, Merlin, results in YAP overexpression and target gene transcription. This mechanism of dysregulation is described in NF2-driven meningiomas, but further work is necessary to understand the NF2-independent mechanism of tumorigenesis. Amid our institutional patient-centric comprehensive molecular profiling study, we identified an individual with meningioma harboring a YAP1-FAM118Bfusion, previously reported only in supratentorial ependymoma. The tumor histopathology was remarkable, characterized by prominent islands of calcifying fibrous nodules within an overall collagen-rich matrix. To gain insight into this finding, we subsequently evaluated the genetic landscape of 11 additional pediatric and adolescent/young adulthood meningioma patients within the Children’s Brain Tumor Tissue Consortium. A second individual harboring a YAP1-FAM118Bgene fusion was identified within this database. Transcriptomic profiling suggested that YAP1-fusion meningiomas are biologically distinct from NF2-driven meningiomas. Similar to other meningiomas, however, YAP1-fusion meningiomas demonstrated overexpression of EGFRand MET. DNA methylation profiling further distinguished YAP1-fusion meningiomas from those observed in ependymomas. In summary, we expand the genetic spectrum of somatic alteration associated with NF2wild-type meningioma to include the YAP1-FAM118Bfusion and provide support for aberrant signaling pathways potentially targetable by therapeutic intervention.

The primary objective of this study is to segment the uterine fibroids (leiomyoma) from the ultrasound images of the uterus through semantic segmentation, followed by second-order statistical feature extraction using the Gray-level Co-occurrence Matrix (GLCM). The next objective of the study is to compare the performance of the state-of-the-art method namely Vision Transformer (ViT) with three different machine learning (ML) classifiers such as the Support Vector Machine (SVM), Logistic Regression (LR) and k-Nearest Neighbor (k-NN) to classify the images into uterine fibroid and normal. The dataset consists of 50 ultrasound images of uterine fibroids and 50 normal images. Then the images are segmented using region-growing-based semantic segmentation followed by feature extraction and classification using the ML and deep learning (DL) classifiers. Among the ML classifiers, SVM produced a good accuracy of 93.1% compared to the other classifiers. ViT produced an excellent classification accuracy of 97.5%. Hence, ViT outperformed compared to the ML classifiers in uterine fibroid detection. These findings have important implications for clinical practice, as they could help physicians to diagnose and treat uterine fibroids more effectively.

Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy harboring IDH2R172 mutations in >80% cases. We explored the potential of genome-wide DNA methylation profiling to elucidate tumor biology and improve the diagnosis of sinonasal undifferentiated carcinoma and its histologic mimics. Forty-two cases, including sinonasal undifferentiated, large cell neuroendocrine, small cell neuroendocrine, and SMARCB1-deficient carcinomas and olfactory neuroblastoma, were profiled by Illumina Infinium Methylation EPIC array interrogating >850,000 CpG sites. The data were analyzed using a custom bioinformatics pipeline. IDH2mutation status was determined by the targeted exome sequencing (MSK-IMPACTTM) in most cases. H3K27 methylation level was assessed by the immunohistochemistry-based H-score. DNA methylation-based semi-supervised hierarchical clustering analysis segregated IDH2 mutants, mostly sinonasal undifferentiated (n= 10) and large cell neuroendocrine carcinomas (n= 4), from other sinonasal tumors, and formed a single cluster irrespective of the histologic type. t-distributed stochastic neighbor embedding dimensionality reduction analysis showed no overlap between IDH2mutants, SMARCB1-deficient carcinoma and olfactory neuroblastoma. IDH2mutants demonstrated a global methylation phenotype and an increase in repressive trimethylation of H3K27 in comparison to IDH2wild-type tumors (p< 0.001). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed no difference in pathway activation between IDH2-mutated sinonasal undifferentiated and large cell neuroendocrine carcinomas. In comparison to SMARCB1-deficient, IDH2-mutated carcinomas were associated with better disease-free survival (p= 0.034) and lower propensity for lung metastasis (p= 0.002). ARID1Amutations were common in small cell neuroendocrine carcinoma but not among IDH2mutants (3/3 versus 0/18 and p< 0.001). IDH2mutations in sinonasal carcinomas induce a hypermethylator phenotype and define a molecular subgroup of tumors arising in this location. IDH2-mutated sinonasal undifferentiated carcinoma and large cell neuroendocrine carcinoma likely represent a phenotypic spectrum of the same entity, which is distinct from small cell neuroendocrine and SMARCB1-deficient sinonasal carcinomas. DNA methylation-based analysis of the sinonasal tumors has potential to improve the diagnostic accuracy and classification of tumors arising in this location.

IMPORTANCE: Understanding eye care use over time is essential to estimate continued unmet health care needs and help guide future public health priorities. OBJECTIVE: To update trends in using eye care and affording eyeglasses in the United States. DESIGN, SETTING, AND PARTICIPANTS: This analysis of data from the US National Health Interview Survey included adults 18 years and older from 9 annual cross-sectional population-based samples ranging in size from 21 781 to 36 697 participants from 2008 to 2016. Data were analyzed from August 2017 to February 2018. EXPOSURES: Visual impairment, defined as self-reported difficulty seeing despite wearing eyeglasses. MAIN OUTCOMES AND MEASURES: Outcome measures included visits to an eye care professional and inability to afford eyeglasses when needed in the past year. Survey logistic regression, adjusted for age, sex, race/ethnicity, visual impairment status, education, employment, general health, poverty-income ratio, and vision insurance, was used to examine associations between survey year and eye care outcomes. RESULTS: Analyses included 9 annual cross-sectional population-based samples pooled from 2008 to 2016, ranging in size from 21 781 to 36 697 participants aged 18 years or older. Compared with 2008, greater proportions of the US population were 65 years or older, Hispanic, or Asian in 2016. There was a significant trend for eye care use and difficulty affording eyeglasses from 2008 to 2016. In fully adjusted models, Americans were less likely to use eye care in 2014 compared with 2008 (odds ratio [OR], 0.90; 99.9% CI, 0.82-0.98; P &lt; .001). Compared with 2008, Americans were also less likely to report difficulty affording eyeglasses from 2014 onwards (2014: OR, 0.82; 99.9% CI, 0.69-0.97; P &lt; .001; 2015: OR, 0.81; 99.9% CI, 0.69-0.96; P &lt; .001; 2016: OR, 0.70; 99.9% CI, 0.59-0.82; P &lt; .001). After adjusting for all covariates, including survey year, those with visual impairment compared with those without were more likely to use eye care (OR, 1.54; 99.9% CI, 1.45-1.65; P &lt; .001) but had greater difficulty affording eyeglasses (OR, 3.86; 99.9% CI, 0.58-0.72; P &lt; .001). Women were also more likely to use eye care (OR, 1.42; 99.9% CI, 1.37-1.48; P &lt; .001) and report difficulty affording eyeglasses (OR, 1.68; 99.9% CI, 1.56-1.81; P &lt; .001) compared with men. Compared with non-Hispanic white individuals, black, Asian, and Hispanic individuals were less likely to use eye care, and Asian and black individuals were less likely to have difficulty affording eyeglasses. CONCLUSIONS AND RELEVANCE: These data indicate decreased difficulty affording eyeglasses among Americans from 2014 to 2016, possibly related to economic recovery and health care reform. However, the findings suggest women and racial/ethnic minorities are more likely to have lower use of eye care or inability to afford eyeglasses.

BCOR is an epigenetic regulator and is genetically altered by mutation, deletion, or gene fusion in a range of cancers. "Central nervous system high-grade neuroepithelial tumor with BCOR alteration" is a recently described entity with characteristic internal tandem duplications within exon 15 of the BCOR gene (hereafter: CNS HGNET-BCOR ex15 ITD). In this case series of 3 patients, we report the clinicopathologic, molecular, and methylome features of gliomas with novel EP300-BCOR in-frame gene fusions, thus expanding the spectrum of BCOR alterations seen in CNS tumors. The gliomas in this series arise in children (ages 10-18), involve the supratentorial compartment, and have an infiltrative pattern of growth and a myxoid/microcystic background with frequent psammomatous calcifications and prominent chicken-wire vessels. All 3 cases had areas with low-grade morphology and 2 of them demonstrated histologic high-grade transformation. In contrast to CNS HGNET-BCOR ex15 ITD, they lack perivascular pseudorosettes. On a t-Distributed Stochastic Neighbor Embedding plot they cluster perfectly together, away from CNS HGNET-BCOR ex15ITD, consistent with a different entity. Gliomas with EP300-BCOR fusions and high-grade histology can demonstrate relatively rapid regrowth after debulking or subtotal resection.

Superficial/cutaneous malignant peripheral nerve sheath tumor is a rare soft tissue neoplasm that shares morphological, immunohistochemical, and molecular features with spindle/desmoplastic melanoma. We aimed to identify a methylome signature to distinguish these two entities. We analyzed 15 cases of spindle/desmoplastic melanoma and 15 cases of cutaneous malignant peripheral nerve sheath tumor in 23 men and 7 women. DNA from formalin-fixed, paraffin-embedded tissues was extracted and processed using the Illumina Infinium Methylation EPIC array interrogating 866,562 CpG sites. Using a home-grown informatics pipeline, we identified differentially methylated positions between the two entities. Functional network analysis for enrichment signatures was performed using DAVID tools. Identified differentially methylated positions were compared with the Cancer Genome Atlas's cutaneous melanoma dataset and a recently published malignant peripheral nerve sheath tumor dataset to assess the specificity of the identified signature. Unsupervised hierarchical clustering showed different patterns of methylation in cutaneous malignant peripheral nerve sheath tumor and spindle/desmoplastic melanoma. Two probes, cg20783223 and cg13332552, colocalized in the promoter region of BCAT1and miR-2504. Pathway analysis highlighted enrichment in a subset of genes involved in breast and gastric cancer centered on BCAT1and downstream activated genes in the mTOR pathway. Our study identifies BCAT1as a novel methylome signature distinguishing spindle/desmoplastic melanoma from cutaneous malignant peripheral nerve sheath tumor.

IMPORTANCE: While dosing reminders for glaucoma medications have been shown to increase drug adherence, an outstanding limitation preventing broad adoption is difficulty linking reminders to medication in each patient’s electronic health record (EHR). OBJECTIVE: To examine the feasibility of implementing an EHR-linked, automated reminder system for glaucoma medications and assess patient satisfaction with it. DESIGN, SETTING, AND PARTICIPANTS: In this prospective, cross-sectional study, patients receiving glaucoma medications were recruited from a university-based glaucoma clinic from April 2017 to January 2018. Analysis began in February 2018. EXPOSURES: A web-based application was added to the EHR patient portal, allowing patients to configure telecommunication-based reminders for their glaucoma medications. For all potential participants, basic information was collected to determine risk of nonadherence with glaucoma medications. Those consenting to participate then answered questions on medication adherence, reminders, and their likelihood of using EHR-linked reminders. They then configured reminders using the EHR patient portal. After 3 months, they answered questions about their satisfaction with the system. MAIN OUTCOMES AND MEASURES: Proportions of patients and high-risk patients willing to use the reminders, and patient satisfaction with the system. RESULTS: Of 147 patients approached, 100 (68%) agreed to participate, of whom the majority were men (54 [54%]) and white (51 [51%]), with a mean (SD) age of 65 (12.4) years. There were no differences between those willing and unwilling to participate, except for a slightly lower self-reported medication adherence rate among those who participated (mean [SD], 91% [13.6%] vs 97% [6.0%]). Based on a previously validated risk assessment score, 9% (9 of 100) of participants were categorized as being at high risk for poor adherence (≥50% probability of nonadherence) compared with 11% (5 of 47) of nonparticipants. Of 100 participants, 94 ultimately configured reminders, of whom 89 (95%) completed follow-up. On follow-up, 74% (n = 66; 95% CI, 65-83) of participants found the reminders to be useful, 15% (n = 13) were neutral, and 11% (n = 10) found them not useful. Most participants (72 [81%]; 95% CI, 77-85) had help configuring reminders. CONCLUSIONS AND RELEVANCE: Electronic health records–linked reminders had good uptake and were well received among patients at a tertiary glaucoma clinic. These portals may represent a new and convenient method of allowing patients to link their glaucoma medications to automated reminders, although the generalizability of these results and the effect on glaucoma outcomes remains unknown.