Navigating Practice Issues Related to the Unsatisfactory Cervicovaginal Papanicolaou Test: Survey Results of Laboratories Participating in the 2020 College of American Pathologists PAP Education Program.

CONTEXT.­: Unsatisfactory Papanicolaou (Pap) tests pose a unique set of challenges to the laboratory with regard to their processing, review, reporting, and performance of human papillomavirus (HPV) testing. There are no standardized guidelines for the review process and handling of unsatisfactory Pap tests. OBJECTIVE.­: To assess the current practice patterns regarding various aspects of the unsatisfactory Pap test, from processing to reporting, across laboratories worldwide. DESIGN.­: A supplemental questionnaire was mailed to laboratories participating in the 2020 College of American Pathologists (CAP) Gynecologic Cytopathology (PAP Education) Program, requesting data regarding the unsatisfactory Pap test. RESULTS.­: Of 1520 participating laboratories, 619 (40.7%) responded, and the responses of 577 laboratories were included for further analysis. Only 64.6% (373 of 577) laboratories used the unsatisfactory Pap test criteria as specified by the 2014 Bethesda System. About three-quarters of the respondents (433 of 576; 75.2%) routinely rescreened unsatisfactory Pap tests. Routine repreparation of such Pap tests was performed by 54.9% (316 of 576) of laboratories, and 52.0% (293 of 563) used glacial acetic acid for repreparing excessively bloody specimens. HPV test results were reported for unsatisfactory Pap tests, always or sometimes, by 62.4% (353 of 566) of respondents. CONCLUSIONS.­: This CAP survey reveals important information regarding the practice patterns pertaining to several aspects of the unsatisfactory Pap test. It also provides valuable insight into the quality assurance measures that can be implemented for such tests. Future studies can further aid in the standardization of all components of the handling of unsatisfactory Pap tests for overall quality improvement.

Cytologic-Histologic Correlation Practices for Nongynecologic Cytology Specimens: A Survey by the College of American Pathologists Cytopathology Committee.

CONTEXT.­: Cytologic-histologic correlation (CHC) is a Clinical Laboratory Improvement Amendments-mandated requirement for gynecologic cytology, but no similar requirement exists for nongynecologic cytology. This study presents the findings from a College of American Pathologists' survey of nongynecologic cytology practice patterns. OBJECTIVE.­: To survey the current CHC practices for nongynecologic cytology. DESIGN.­: Data were analyzed from a survey developed by the committee and distributed to participants in the Nongynecologic Cytopathology Education Program mailing. RESULTS.­: Adoption of CHC for nongynecologic cytology cases is worldwide, with 88.5% of institutions performing CHC on these specimens, a substantial increase from previous years. Performance of CHC varied by institution type, with clinic or regional/local independent laboratories and national/corporate laboratories performing CHC significantly less frequently than hospitals, university hospitals/academic medical centers, and Veterans Administration/Department of Defense hospital institutions. Most CHC was performed concurrently in real time, when the corresponding surgical specimen was reviewed. Selection for real-time concurrent CHC was by the interpreting pathologist, the pathologist diagnosing the surgical biopsy sample or cytopathology case, or both. Sampling was by far the most common reason for discordance. A 2-step difference was the most frequent threshold for discordance between cytology and surgical specimens, but this criterion varied among institutions, with no majority definition. The positive predictive value of a positive cytology finding was calculated rarely in North American institutions but was calculated more frequently in international institutions. CONCLUSIONS.­: CHC practices for nongynecologic cytopathology mirror those found for CHC of gynecologic cytopathology.

Streamlining apartment provider evaluation: A spherical fuzzy multi-criteria decision-making model.

In the context of the thriving real estate market in developing countries like Vietnam, understanding consumer preferences and effectively addressing them through a comprehensive multi-criteria decision-making (MCDM) framework is paramount for real estate providers. This study presents a two-stage MCDM model that integrates the Delphi technique and the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) based on Spherical Fuzzy Sets (SFSs). Initially, the SF-Delphi technique validates critical criteria influencing customers' apartment selection in Vietnam. Secondly, the SF-TOPSIS method evaluates the top ten apartment providers. To ensure robustness and validity, a comparative analysis compares the results with those from the Intuitionistic Fuzzy TOPSIS (IF-TOPSIS) and Fuzzy TOPSIS (F-TOPSIS) methods. Subsequently, five rank correlation coefficients (Spearman, Kendall, Goodman-Kruskal, Weighted rank measure of correlation, Weighted Similarity) are used to assess the relationships between various TOPSIS techniques applied to apartment suppliers in Vietnam. The correlation coefficients demonstrate strong agreement among the TOPSIS methods, with the smallest coefficient being 0.7778, surpassing the threshold of 0.7. This high level of consistency confirms the efficacy of the proposed TOPSIS approach with different Fuzzy Sets in reliably evaluating customers' preferences for apartment suppliers. Notably, the legal aspect's prominence underscores its critical role in shaping customer choices, emphasizing the significance of considering legal factors in the context of apartment supply and demand in Vietnam. Furthermore, using SFSs makes this approach particularly suited to capture consumer perceptions within the dynamic and uncertain business environment characterized by volatility, uncertainty, complexity, and ambiguity (VUCA).

Pancreaticobiliary Cytology Practice in 2021: Results of a College of American Pathologists Survey.

CONTEXT.­: The College of American Pathologists (CAP) surveys provide national benchmarks of pathology practice. OBJECTIVE.­: To investigate pancreaticobiliary cytology practice in domestic and international laboratories in 2021. DESIGN.­: We analyzed data from the CAP Pancreaticobiliary Cytology Practice Supplemental Questionnaire that was distributed to laboratories participating in the 2021 CAP Nongynecologic Cytopathology Education Program. RESULTS.­: Ninety-three percent (567 of 612) of respondent laboratories routinely evaluated pancreaticobiliary cytology specimens. Biliary brushing (85%) was the most common pancreaticobiliary cytology specimen evaluated, followed by pancreatic fine-needle aspiration (79%). The most used sampling methods reported by 235 laboratories were 22-gauge needle for fine-needle aspiration (62%) and SharkCore needle for fine-needle biopsy (27%). Cell block was the most used slide preparation method (76%), followed by liquid-based cytology (59%) for pancreatic cystic lesions. Up to 95% (303 of 320) of laboratories performed rapid on-site evaluation (ROSE) on pancreatic solid lesions, while 56% (180 of 320) performed ROSE for cystic lesions. Thirty-six percent (193 of 530) of laboratories used the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology in 2021. Among all institution types, significant differences in specimen volume, specimen type, ROSE practice, and case sign-out were identified. Additionally, significant differences in specimen type, slide preparation, and ROSE practice were found. CONCLUSIONS.­: This is the first survey from the CAP to investigate pancreaticobiliary cytology practice. The findings reveal significant differences among institution types and between domestic and international laboratories. These data provide a baseline for future studies in a variety of practice settings.

The Implementation of Nongynecologic Reporting Systems in Cytopathology Laboratories Is Highly Variable: Analysis of Data From a 2020 Supplemental Survey of Participants in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT­: In recent years, several reporting systems have been developed by national and international cytopathology organizations to standardize the evaluation of specific cytopathology specimen types. OBJECTIVE­: To assess the current implementation rates, implementation methods, and barriers to implementation of commonly used nongynecologic reporting systems in cytopathology laboratories. DESIGN­: Data were analyzed from a survey developed by the committee and distributed to participants in the College of American Pathologists Nongynecologic Cytopathology Education Program mailing. RESULTS­: Nongynecologic reporting systems with the highest rate of adoption were the Bethesda System for Reporting Thyroid Cytopathology, 2nd edition (74.1%; 552 of 745); the Paris System for Reporting Urinary Cytology (53.9%; 397 of 736); and the Milan System for Reporting Salivary Gland Cytopathology (29.1%; 200 of 688). The most common reason given for not adopting a reporting system was satisfaction with a laboratory's current system. Implementation varied among laboratories with regard to which stakeholders were involved in deciding to implement a system and the amount of education provided during the implementation process. CONCLUSIONS­: The implementation of nongynecologic reporting systems in cytopathology laboratories was highly variable.

Retrocorneal fibrous membrane after phacoemulsification in an eye with pseudoexfoliative glaucoma.

OBJECTIVE: To report a case of a retrocorneal fibrous membrane and corneal decompensation following uncomplicated phacoemulsification in an eye with pseudoexfoliative glaucoma. METHOD: Case report and literature review. RESULTS: A monocular 83-year-old female developed corneal decompensation 1 year after uncomplicated cataract extraction via phacoemulsification. She had a history of pseudoexfoliative glaucoma and had undergone 3 rounds of selective laser trabeculoplasty in the same eye 3 years prior. Given the resulting corneal edema, the patient underwent Descemet's membrane endothelial keratoplasty, at which time a retrocorneal fibrous membrane was identified. Peeling of the membrane was surgically challenging and resulted in an intraocular hemorrhage intraoperatively and a small iridodialysis because the membrane had extended over the angle and iris. Postoperatively, the cornea cleared well, and vision improved significantly. However, vision was ultimately limited by macular pathology. Pathologic examination demonstrated Descemet's membrane with an attached fibrocellular membrane. Immunostaining for smooth muscle actin was positive within the membrane compatible with a retrocorneal membrane. We also present a review of the literature on modern causes of retrocorneal fibrous membranes. CONCLUSIONS: Retrocorneal fibrous membranes are encountered most commonly following corneal transplantation and may be surgically challenging to remove. We present the first case of a pathologically proven retrocorneal fibrous membrane following uncomplicated cataract surgery via phacoemulsification and selective laser trabeculoplasty.

Timeliness of Multimodal Care for At-Risk Breast Cancer Patients at a Safety Net Institution.

INTRODUCTION: Because limited data exist, we sought to evaluate timeliness of multimodal treatments in a safety net breast cancer population. METHODS: Breast cancer patients treated at a safety net hospital from 2016 to 2020 were analyzed retrospectively. Time intervals were defined as primary time (PT) from diagnosis to initiation of primary intervention, secondary time (ST) from completion of primary to initiation of secondary intervention, and tertiary time (TT) from completion of secondary to initiation of tertiary intervention. Variables included primary language, insurance type, and race. RESULTS: Of 223 patients, 99 (44.4%) primarily spoke Spanish, 29 (13.0%) were of Black race, and 184 (82.5%) had Medicaid or uninsured status. Median (IQR) age at diagnosis was 55 (48-62) years. Primary intervention was surgical in 127/216 (58.8%); secondary intervention was systemic in 38/169 (22.5%); and tertiary intervention was radiation in 67/80 (83.8%). Overall, median days (IQR) for PT were 69 (53, 98), ST were 65 (42, 95), and TT were 69 (43, 88). PT was significantly longer in Black [105 (76, 142) days] patients compared to non-Hispanic White patients [68 (51, 107) days, P = 0.031)] and White Hispanic patients [65 (53,91) days, P = 0.014]. There were no significant differences in PT, ST, or TT by spoken language or insurance type. CONCLUSIONS: Black patients remain at risk due to prolonged time to intervention. Spanish-speaking status was not associated with inferior timeliness or completion of multimodal care at a safety net hospital. Identifying safety net hospital barriers to achieving benchmarks for timely completion of all phases of multimodal care warrants further attention.

Aortic Stiffness Measured from Either 2D/4D Flow and Cine MRI or Applanation Tonometry in Coronary Artery Disease: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Aortic stiffness can be evaluated by aortic distensibility or pulse wave velocity (PWV) using applanation tonometry, 2D phase contrast (PC) MRI and the emerging 4D flow MRI. However, such MRI tools may reach their technical limitations in populations with cardiovascular disease. Accordingly, this work focuses on the diagnostic value of aortic stiffness evaluated either by applanation tonometry or MRI in high-risk coronary artery disease (CAD) patients. METHODS: 35 patients with a multivessel CAD and a myocardial infarction treated 1 year before were prospectively recruited and compared with 18 controls with equivalent age and sex distribution. Ascending aorta distensibility and aortic arch 2D PWV were estimated along with 4D PWV. Furthermore, applanation tonometry carotid-to-femoral PWV (cf PWV) was recorded immediately after MRI. RESULTS: While no significant changes were found for aortic distensibility; cf PWV, 2D PWV and 4D PWV were significantly higher in CAD patients than controls (12.7 ± 2.9 vs. 9.6 ± 1.1; 11.0 ± 3.4 vs. 8.0 ± 2.05 and 17.3 ± 4.0 vs. 8.7 ± 2.5 m·s-1 respectively, p < 0.001). The receiver operating characteristic (ROC) analysis performed to assess the ability of stiffness indices to separate CAD subjects from controls revealed the highest area under the curve (AUC) for 4D PWV (0.97) with an optimal threshold of 12.9 m·s-1 (sensitivity of 88.6% and specificity of 94.4%). CONCLUSIONS: PWV estimated from 4D flow MRI showed the best diagnostic performances in identifying severe stable CAD patients from age and sex-matched controls, as compared to 2D flow MRI PWV, cf PWV and aortic distensibility.

Hydroxymethylation alterations in progenitor-like cell types of pediatric central nervous system tumors are associated with cell type-specific transcriptional changes.

Although intratumoral heterogeneity has been established in pediatric central nervous system tumors, epigenomic alterations at the cell type level have largely remained unresolved. To identify cell type-specific alterations to cytosine modifications in pediatric central nervous system tumors we utilized a multi-omic approach that integrated bulk DNA cytosine modification data (methylation and hydroxymethylation) with both bulk and single-cell RNA-sequencing data. We demonstrate a large reduction in the scope of significantly differentially modified cytosines in tumors when accounting for tumor cell type composition. In the progenitor-like cell types of tumors, we identified a preponderance differential CpG hydroxymethylation rather than methylation. Genes with differential hydroxymethylation, like HDAC4 and IGF1R, were associated with cell type-specific changes in gene expression in tumors. Our results highlight the importance of epigenomic alterations in the progenitor-like cell types and its role in cell type-specific transcriptional regulation in pediatric CNS tumors.

Tumor type and cell type-specific gene expression alterations in diverse pediatric central nervous system tumors identified using single nuclei RNA-seq.

Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collected single nuclei RNA-seq data from 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues (84,700 nuclei) and characterized tumor heterogeneity and transcriptomic alterations. We distinguished cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observed pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identified transcriptomic alterations among pediatric CNS tumor types compared to non-tumor tissues, while accounting for cell type effects on gene expression. Our results suggest potential tumor type and cell type-specific targets for pediatric CNS tumor treatment. In this study, we address current gaps in understanding single nuclei gene expression profiles of previously uninvestigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.

Thermal degradation and flame retardancy of nylon 6/aluminum methylmethoxy phosphonate composites.

An aluminum methylmethoxyphosphonate (AlPo)-based flame retardant (FR) was synthesized. Thermal degradation and flame retardancy of nylon 6 (PA6)/AlPo composites were examined and compared with PA6/commercial aluminum diethylphosphinate (AlPi) composites. The PA6/AlPo composite achieved a V-0 rating at 20 wt% loading during the UL-94 test, and it exhibited the formation of a charred layer that protected the polymer from burning and reduced the release of gases during the combustion of PA6. AlPo demonstrated exceptional performance in gaseous and condensed phases in the PA6 matrix, whereas AlPi only worked in the gaseous phase. The differences between the thermal degradation mechanisms and flame retardancies of AlPi and AlPo were investigated via Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and cone calorimetry. A suitable degradation mechanism was proposed to aid the development of flame retardants in the future.

Current State of Cytologic-Histologic Correlation Implementation for North American and International Laboratories: Results of the College of American Pathologists Cytopathology Committee Laboratory Practices in Gynecologic Cytology Survey.

CONTEXT.­: The College of American Pathologists (CAP) updated the Laboratory Accreditation Program Cytopathology Checklist to assist laboratories in meeting and exceeding the Clinical Laboratory Improvement Amendments standards for gynecologic cytologic-histologic correlation (CHC). OBJECTIVE.­: To survey the current CHC practices. DESIGN.­: Data were analyzed from a survey developed by the committee and distributed to participants in the CAP Gynecologic Cytopathology PAP Education Program mailing. RESULTS.­: Worldwide, CHC practice is nearly universally adopted, with an overall rate of 87.0% (568 of 653). CHC material was highly accessible. CHC was commonly performed real time/concurrently at the time the corresponding surgical pathology was reviewed. Investigation of CHC discordances varied with North American laboratories usually having a single pathologist review all discrepant histology and cytology slides to determine the reason for discordance, while international laboratories have a second pathologist review histology slides to determine the reason for discordance. The cause of CHC discordance was primarily sampling issues. The more common statistical metrics for CHC monitoring were the total percentage of cases that correlated with subsequent biopsies, screening error rate by cytotechnologist, and interpretative error rate by cytotechnologist. CONCLUSIONS.­: Many laboratories have adopted and implemented the CHC guidelines with identifiable differences in practices between North American and international laboratories. We identify the commonalities and differences between North American and international institutional practices including where CHC is performed, how CHC cases are identified and their accessibility, when CHC is performed, who investigates discordances, what discordances are identified, and how the findings affect quality improvement.

Using American Type Culture Collection Cell Lines to Evaluate Interlaboratory Variables for Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Immunostaining.

CONTEXT.­: Most laboratories currently use patient tissues for validating immunohistochemical stains. OBJECTIVE.­: To explore advantages of using cell lines with known antigenicity as a validation method. DESIGN.­: Five American Type Culture Collection (ATCC) cell lines with known negative, low positive, and moderate to strong estrogen receptor (ER) expression as well as negative, equivocal, and positive human epidermal growth factor receptor 2 (HER2) expression were cultured and made into cell blocks. One block from each cell line was fixed in formalin and another in ethanol before cell block preparation. Two sets of paired unstained slides from each block were sent to 10 different laboratories for HER2 and ER staining to be stained on runs from different days according to each laboratory's defined protocol. RESULTS.­: The 10 study participants evaluated 40 slides in a blinded fashion. For ER expression, all 80 interpretations for the ER strong and moderate positive cell lines had the target ER-positive result, and 74 of 80 ER-negative cell lines (92.5%) had agreement with the intended negative result. The ER low positive cell line showed varied but positive expression among all observers. The HER2 (3+)-positive cell lines yielded a target interpretation of 3+ in 65 of 80 interpretations (81.2%). For the HER2-negative cell line 69 of 78 interpretations (88.5%) were consistent with the target response (0 or 1+). No significant variation was observed between the ethanol- and non-ethanol-exposed cell lines, or between runs by the same laboratory. Variation from target results clustered within laboratories. CONCLUSIONS.­: This study indicates that variability between laboratories can be identified by using cell lines for quantitative or semiquantitative immunohistochemistry when using cultured cell lines of known antigenicity. These cell lines could potentially play a role in aiding anatomic pathology laboratories in validating immunohistochemistry tests for formalin- and ethanol-fixed tissues.

A Natural History of Patients Treated Operatively and Nonoperatively for Spinal Metastases Over 2 Years Following Treatment: Survival and Functional Outcomes.

STUDY DESIGN: Prospective observational study. OBJECTIVE: We present the natural history, including survival and function, among participants in the prospective observational study of spinal metastases treatment investigation. SUMMARY OF BACKGROUND DATA: Surgical treatment has been touted as a means to preserve functional independence, quality of life, and survival. Nearly all prior investigations have been limited by retrospective design and relatively short-periods of post-treatment surveillance. METHODS: This natural history study was conducted using the records of patients who were enrolled in the prospective observational study of spinal metastases treatment study (2017-2019). Eligible participants were 18 or older and presenting for treatment of spinal metastatic disease. Patients were followed at predetermined intervals (1, 3, 6, 12, and 24-mo) following treatment. We conducted cox proportional hazard regression analysis adjusting for confounders including age, biologic sex, number of comorbidities, type of metastatic lesion, neurologic symptoms at presentation, number of metastases involving the vertebral body, vertebral body collapse, New England Spinal Metastasis Score (NESMS) at presentation, and treatment strategy. RESULTS: We included 202 patients. Twenty-three percent of the population had died by 3 months following treatment initiation, 51% by 1 year, and 70% at 2 years. There was no significant difference in survival between patients treated operatively and nonoperatively (P = 0.16). No significant difference in HRQL between groups was appreciated beyond 3 months following treatment initiation. NESMS at presentation (scores of 0 [HR 5.61; 95% CI 2.83, 11.13] and 1 [HR 3.00; 95% CI 1.60, 5.63]) was significantly associated with mortality. CONCLUSION: We found that patients treated operatively and nonoperatively for spinal metastases benefitted from treatment in terms of HRQL. Two-year mortality for the cohort as a whole was 70%. When prognosticating survival, the NESMS appears to be an effective utility, particularly among patients with scores of 0 or 1.Level of Evidence: 2.

Prospective comparison of the accuracy of the New England Spinal Metastasis Score (NESMS) to legacy scoring systems in prognosticating outcomes following treatment of spinal metastases.

BACKGROUND CONTEXT: We developed the New England Spinal Metastasis Score (NESMS) as a simple, informative, scoring scheme that could be applied to both operative and non-operative patients. The performance of the NESMS to other legacy scoring systems has not previously been compared using appropriately powered, prospectively collected, longitudinal data. PURPOSE: To compare the predictive capacity of the NESMS to the Tokuhashi, Tomita and Spinal Instability Neoplastic Score (SINS) in a prospective cohort, where all scores were assigned at the time of baseline enrollment. PATIENT SAMPLE: We enrolled 202 patients with spinal metastases who met inclusion criteria between 2017-2019. OUTCOME MEASURES: One-year survival (primary); 3-month mortality and ambulatory function at 3- and 6-months were considered secondarily. METHODS: All prognostic scores were assigned based on enrollment data, which was also assigned as time-zero. Patients were followed until death or survival at 365 days after enrollment. Survival was assessed using Kaplan-Meier curves and score performance was determined via logistic regression testing and observed to expected plots. The discriminative capacity (c-statistic) of the scoring measures were compared via the z-score. RESULTS: When comparing the discriminative capacity of the predictive scores, the NESMS had the highest c-statistic (0.79), followed by the Tomita (0.69), the Tokuhashi (0.67) and the SINS (0.54). The discriminative capacity of the NESMS was significantly greater (p-value range: 0.02 to <0.001) than any of the other predictive tools. The NESMS was also able to inform independent ambulatory function at 3- and 6-months, a function that was only uniformly replicated by the Tokuhashi score. CONCLUSIONS: The results of this prospective validation study indicate that the NESMS was able to differentiate survival to a significantly higher degree than the Tokuhashi, Tomita and SINS. We believe that these findings endorse the utilization of the NESMS as a prognostic tool capable of informing care for patients with spinal metastases.

Characterizing Health-Related Quality of Life by Ambulatory Status in Patients with Spinal Metastases.

STUDY DESIGN: Retrospective review of prospective longitudinal data. OBJECTIVE: To determine health-related quality of life (HRQL) utilities associated with specific ambulatory states in patients with spinal metastases: independent, ambulatory with assistance, and nonambulatory. SUMMARY OF BACKGROUND DATA: It is assumed that HRQL is aligned with ambulatory ability in patients with spinal metastases. Few studies have effectively considered these parameters while also accounting for clinical confounders. METHODS: We used prospective longitudinal data from patients treated at one of three tertiary medical centers (2017-2019). HRQL was characterized using the Euroquol-5-dimension (EQ5D) inventory. We performed standardized estimations of HRQL stratified by ambulatory state using generalized linear modeling that accounted for patient age at presentation, biologic sex, follow-up duration, operative or nonoperative management, and repeated measures within the same participant. RESULTS: We evaluated 675 completed EQ5D assessments, with 430 for independent ambulators, 205 for ambulators with assistance, and 40 for nonambulators. The average age of the cohort was 61.5. The most common primary cancer was lung (20%), followed by breast (18%). Forty-one percent of assessments were performed for participants treated surgically. Mortality occurred in 51% of the cohort. The standardized EQ5D utility for patients with spinal metastases and independent ambulatory function was 0.76 (95% confidence interval [CI] 0.74, 0.78). Among those ambulatory with assistance, the standardized EQ5D utility was 0.59 (95% CI 0.57, 0.61). For nonambulators, the standardized EQ5D utility was 0.14 (95% CI 0.09, 0.19). CONCLUSION: Patients with spinal metastases and independent ambulatory function have an HRQL similar to patients with primary cancers and no spinal involvement. Loss of ambulatory ability leads to a 22% decrease in HRQL for ambulation with assistance and an 82% reduction among nonambulators. Given prior studies demonstrate superior maintenance of ambulatory function with surgery for spinal metastases, our results support surgical consideration to the extent that it is clinically warranted.Level of Evidence: 3.

Spin-Selective Hole-Exciton Coupling in a V-Doped WSe2 Ferromagnetic Semiconductor at Room Temperature.

While valley polarization with strong Zeeman splitting is the most prominent characteristic of two-dimensional (2D) transition metal dichalcogenide (TMD) semiconductors under magnetic fields, enhancement of the Zeeman splitting has been demonstrated by incorporating magnetic dopants into the host materials. Unlike Fe, Mn, and Co, V is a distinctive dopant for ferromagnetic semiconducting properties at room temperature with large Zeeman shifting of band edges. Nevertheless, little known is the excitons interacting with spin-polarized carriers in V-doped TMDs. Here, we report anomalous circularly polarized photoluminescence (CPL) in a V-doped WSe2 monolayer at room temperature. Excitons couple to V-induced spin-polarized holes to generate spin-selective positive trions, leading to differences in the populations of neutral excitons and trions between left and right CPL. Using transient absorption spectroscopy, we elucidate the origin of excitons and trions that are inherently distinct for defect-mediated and impurity-mediated trions. Ferromagnetic characteristics are further confirmed by the significant Zeeman splitting of nanodiamonds deposited on the V-doped WSe2 monolayer.

DNA 5-hydroxymethylcytosine in pediatric central nervous system tumors may impact tumor classification and is a positive prognostic marker.

BACKGROUND: Nucleotide-specific 5-hydroxymethylcytosine (5hmC) remains understudied in pediatric central nervous system (CNS) tumors. 5hmC is abundant in the brain, and alterations to 5hmC in adult CNS tumors have been reported. However, traditional approaches to measure DNA methylation do not distinguish between 5-methylcytosine (5mC) and its oxidized counterpart 5hmC, including those used to build CNS tumor DNA methylation classification systems. We measured 5hmC and 5mC epigenome-wide at nucleotide resolution in glioma, ependymoma, and embryonal tumors from children, as well as control pediatric brain tissues using tandem bisulfite and oxidative bisulfite treatments followed by hybridization to the Illumina Methylation EPIC Array that interrogates over 860,000 CpG loci. RESULTS: Linear mixed effects models adjusted for age and sex tested the CpG-specific differences in 5hmC between tumor and non-tumor samples, as well as between tumor subtypes. Results from model-based clustering of tumors was used to test the relation of cluster membership with patient survival through multivariable Cox proportional hazards regression. We also assessed the robustness of multiple epigenetic CNS tumor classification methods to 5mC-specific data in both pediatric and adult CNS tumors. Compared to non-tumor samples, tumors were hypohydroxymethylated across the epigenome and tumor 5hmC localized to regulatory elements crucial to cell identity, including transcription factor binding sites and super-enhancers. Differentially hydroxymethylated loci among tumor subtypes tended to be hypermethylated and disproportionally found in CTCF binding sites and genes related to posttranscriptional RNA regulation, such as DICER1. Model-based clustering results indicated that patients with low 5hmC patterns have poorer overall survival and increased risk of recurrence. Our results suggest 5mC-specific data from OxBS-treated samples impacts methylation-based tumor classification systems giving new opportunities for further refinement of classifiers for both pediatric and adult tumors. CONCLUSIONS: We identified that 5hmC localizes to super-enhancers, and genes commonly implicated in pediatric CNS tumors were differentially hypohydroxymethylated. We demonstrated that distinguishing methylation and hydroxymethylation is critical in identifying tumor-related epigenetic changes. These results have implications for patient prognostication, considerations of epigenetic therapy in CNS tumors, and for emerging molecular neuropathology classification approaches.

Peripheral Nerve Focused Ultrasound Lesioning-Visualization and Assessment Using Diffusion Weighted Imaging.

Objectives: Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive targeted tissue ablation technique that can be applied to the nervous system. Diffusion weighted imaging (DWI) can visualize and evaluate nervous system microstructure. Tractography algorithms can reconstruct fiber bundles which can be used for treatment navigation and diffusion tensor imaging (DTI) metrics permit the quantitative assessment of nerve microstructure in vivo. There is a need for imaging tools to aid in the visualization and quantitative assessment of treatment-related nerve changes in MRgFUS. We present a method of peripheral nerve tract reconstruction and use DTI metrics to evaluate the MRgFUS treatment effect. Materials and Methods: MRgFUS was applied bilaterally to the sciatic nerves in 6 piglets (12 nerves total). T1-weighted and diffusion images were acquired before and after treatment. Tensor-based and constrained spherical deconvolution (CSD) tractography algorithms were used to reconstruct the nerves. DTI metrics of fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivities (RD) were measured to assess acute (<1-2 h) treatment effects. Temperature was measured in vivo via MR thermometry. Histological data was collected for lesion assessment. Results: The sciatic nerves were successfully reconstructed in all subjects. Tract disruption was observed after treatment using both CSD and tensor models. DTI metrics in the targeted nerve segments showed significantly decreased FA and increased MD, AD, and RD. Transducer output power was positively correlated with lesion volume and temperature and negatively correlated with MD, AD, and RD. No correlations were observed between FA and other measured parameters. Conclusions: DWI and tractography are effective tools for visualizing peripheral nerve segments for targeting in non-invasive surgical methods and for assessing the microstructural changes that occur following MRgFUS treatment.

Analysis of Polycyclic Aromatic Hydrocarbon in Airborne Particulate Matter Samples by Gas Chromatography in Combination with Tandem Mass Spectrometry (GC-MS/MS).

Polycyclic aromatic hydrocarbons (PAHs), the family of organic contaminations, have been shown to have negative effects on human health. However, until now, the comprehension on occurrence, distribution, and risk assessment of human exposure to PAHs has been limited in Vietnam. In this work, a capillary gas chromatography coupled with electron impact ionization tandem mass spectrometry (GC-EI-MS/MS) has been introduced for analysis of 16 PAHs in some particulate matter samples. PAHs have been separated on the TG 5 ms capillary gas chromatographic column and detected by tandem mass spectrometry in multiple reaction monitoring mode. The PAHs in the particulate matter (PM 2.5 and PM 10) samples were extracted by ultrasonic-assisted liquid extraction and cleaned up by an acidic silica gel solid phase extraction. The linearity range of all analyzed PAHs was from 5 to 2000 ng mL-1 with R 2 ≥0.9990. Limit of detection (LOD) of PAHs in particulate matter sample was from 0.001 ng m-3 (Br-Naph) to 0.276 ng m-3 (Fln). The recovery of PAHs was investigated by international proficiency testing samples. The recoveries of PAHs in proficiency testing sample ranged from 79.3% (Chr) to 109.8% (IcdP). The in-house validated GC-EI-MS/MS method was then applied to analysis of some particulate matter samples that were collected in the Hanoi areas. The total concentrations of PAHs in several brands of samples collected from Hanoi were found in the range of 226.3 ng m-3-706.43 ng m-3. Among the studied compounds, naphthalene was found at high frequency and ranged from 106.5 ng m-3 to 631.1 ng m-3. The main distribution of the PAHs in particulate matter samples was two-ring and three-ring compounds.