Search

This study investigates the functional significance of assorted variants of uncertain significance (VUS) in euchromatic histone lysine methyltransferase 1 (EHMT1), which is critical for early development and normal physiology. EHMT1 mutations cause Kleefstra syndrome and are linked to various human cancers. However, accurate functional interpretations of these variants are yet to be made, limiting diagnoses and future research. To overcome this, we integrate conventional tools for variant calling with computational biophysics and biochemistry to conduct multi-layered mechanistic analyses of the SET catalytic domain of EHMT1, which is critical for this protein function. We use molecular mechanics and molecular dynamics (MD)-based metrics to analyze the SET domain structure and functional motions resulting from 97 Kleefstra syndrome missense variants within the domain. Our approach allows us to classify the variants in a mechanistic manner into SV (Structural Variant), DV (Dynamic Variant), SDV (Structural and Dynamic Variant), and VUS (Variant of Uncertain Significance). Our findings reveal that the damaging variants are mostly mapped around the active site, substrate binding site, and pre-SET regions. Overall, we report an improvement for this method over conventional tools for variant interpretation and simultaneously provide a molecular mechanism for variant dysfunction.

The Caatinga biome, located in the northeastern region of Brazil, is the most populated dryland region on the planet and extremely vulnerable to land degradation due to climatological and anthropogenic factors. Energy partitioning substantially influences the local climate and affects the water cycle, which is of utmost importance for the economy and livelihood of the region. Recently, eddy covariance (EC) towers were installed in the area; thus, the scientific community can thoroughly assess the water and energy fluxes over this unique biome. While EC towers have a high degree of accuracy, they only measure energy fluxes over a small land footprint. Given the biome spatial heterogeneity, the use of EC-based techniques has the limitation of not comprehensively representing water and energy fluxes profiles over the entire region. Incorporating remote sensing (RS) data into the landscape analysis is a feasible solution to overcome this issue, given that satellite data can capture the phenomena represented by the EC measurements across large spatial scales. Our research studied the capability of the Surface Energy Balance Algorithm for Land (SEBAL) and MOD16-ET products to represent the EC measurements regarding energy and mass exchange, with an ultimate objective of applying the best approach to assess these fluxes regionally. We applied the SEBAL model using only remote sensing data from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor. The MOD16-ET model uses a different approach but is also based on MODIS data. Our analysis was based on three years (2014–2016) of data, which was limited to the availability of the EC tower data. We found that for the EC-based measurements, energy balance closure (EBC) achieved an average of 0.84, which is considerably high for the region. This is possibly due to the EC tower being installed on a preserved Caatinga plot, with reduced heterogeneity and higher plant density. When analyzing RS-based products to represent ET profiles in the region, we found that the SEBAL model accurately represented water fluxes during the wet season but not the dry season, whereas the MOD16-ET showed a better agreement with EC-based water fluxes throughout all the seasons. SEBAL inaccuracy in drylands is partially due to the narrow range between the cold and hot pixels in an image, as the algorithm relies on this range for input parameters, especially in the dry season. Therefore, we concluded that MOD16-ET is capable of better-representing water fluxes in the Caatinga region. We analyzed the fluxes regionally and quantified annual ET for the three years. These results are especially relevant for local policymakers on dealing with water and landscape issues in a region where the livelihood and well-being of the population is inextricably bound to water availability.

Introduction: Cytopathology fellows are required to enter their fine-needle aspiration (FNA) case numbers in an online data collection system, the Accreditation Council for Graduate Medical Education (ACGME) Case Log system. This study reviewed this data to examine trends in FNA case numbers during fellowship training., Methods: A retrospective review of the ACGME Accreditation Data System (ADS) FNA Case Log data was performed for academic years 2006-2019. For 2006-2016, total and average numbers of FNAs performed per academic year were available. After 2016, data also included the number of programs and trainees, national averages, standard deviation, minimum, median, maximum, and percentiles for the number of FNAs performed., Results: The number of FNAs documented by cytopathology fellows has gradually increased from 2006 (average 10.9) to 2013 (average 18.6) and dramatically increased in 2014 (average 38.0). Averages have remained greater than 30 FNAs documented per academic year since 2014, with some variation. However, a decline was observed in 2019, likely due to the COVID-19 pandemic., Conclusions: FNA procedures reported in the ACGME Case Log System indicate vast differences in cytopathology fellowship educational experiences and settings. After logging FNAs becoming an ACGME requirement in 2013, the average number of FNAs has been greater than 30 per year and provides some guidance for programs with respect to the number of FNAs being reported by cytopathology fellows nationally., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Purpose: To review the clinical, radiological, and histopathologic features in 8 patients with natural killer/T-cell lymphoma (NKTL) involving the orbit and/or ocular adnexa, and to describe the responses of these patients to various treatment regimens., Design: Retrospective observational case series., Participants: Eight patients (5 male, 3 female) with NKTL involving the orbit and/or ocular adnexa were identified from 1999 through 2005. The mean age at presentation was 45 years (range, 26-65)., Methods: We retrospectively identified patients with NKTL of the ocular adnexa treated in the authors' medical centers from 1999 through 2004 using computerized diagnostic index retrieval. The clinical records and radiologic studies were analyzed to define modes of presentation and progression, response to therapy, and areas of anatomic involvement. Histopathologic findings, including the presence of CD3, CD56, and Epstein-Barr virus-encoded mRNA in each patient, were reviewed., Main Outcome Measurements: Time of survival from presentation to last known follow-up and tumor-related death., Results: Four of the 8 patients (50%) with NKTL involving the orbit or ocular adnexa had systemic involvement at presentation. Five of the 8 patients (62.5%) had concurrent sinonasal involvement, whereas 3 (37.5%) had orbital involvement alone. All lesions demonstrated CD3, CD56, and/or Epstein-Barr virus positivity on immunopathology studies. Therapy consisted of various chemotherapeutic regimens typically employed in the treatment of non-Hodgkins lymphoma, steroids, surgical intervention, and radiation. Seven (87.5%) patients died 5 weeks to 13 months after presentation, and 1 (12.5%) is alive without disease (5-year follow-up)., Conclusions: Natural killer/T-cell orbital lymphoma is a rare Epstein-Barr virus-associated neoplasm that may occur with or without associated sinonasal involvement. Our series, the largest cohort reported to date, demonstrates the high lethality of this condition despite aggressive conventional therapy, suggesting that new treatment options should be considered early in the course of treatment of patients with this disorder.