Characterization of innate lymphoid cell subsets infiltrating melanoma and epithelial ovarian tumors.

The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity.

Generation of an Inhibitory NK Cell Subset by TGF-ß1/IL-15 Polarization.

NK cells have been shown to exhibit inflammatory and immunoregulatory functions in a variety of healthy and diseased settings. In the context of chronic viral infection and cancer, distinct NK cell populations that inhibit adaptive immune responses have been observed. To understand how these cells arise and further characterize their immunosuppressive role, we examined in vitro conditions that could polarize human NK cells into an inhibitory subset. TGF-ß1 has been shown to induce regulatory T cells in vitro and in vivo; we therefore investigated if TGF-ß1 could also induce immunosuppressive NK-like cells. First, we found that TGF-ß1/IL-15, but not IL-15 alone, induced CD103+CD49a+ NK-like cells from peripheral blood NK cells, which expressed markers previously associated with inhibitory CD56+ innate lymphoid cells, including high expression of GITR and CD101. Moreover, supernatant from ascites collected from patients with ovarian carcinoma also induced CD103+CD49a+ NK-like cells in vitro in a TGF-ß-dependent manner. Interestingly, TGF-ß1/IL-15-induced CD103+CD56+ NK-like cells suppressed autologous CD4+ T cells in vitro by reducing absolute number, proliferation, and expression of activation marker CD25. Collectively, these findings provide new insight into how NK cells may acquire an inhibitory phenotype in TGF-ß1-rich environments.

Hyperuricemia and associated factors: The case of outpatients at the Bafoussam Regional Hospital- Cameroon, an analytical cross-sectional study.

Background and Aims: Hyperuricemia constitutes a major public health issue due to its implication in many chronic diseases and metabolic syndromes. We propose to study the prevalence and associated factors of hyperuricemia to diagnose asymptomatic patients and make prognoses on the state of health of the patients. Methods: An analytic cross-sectional study has been carried out at the Bafoussam Regional Hospital and the Biochemistry laboratory of the Université des Montagnes over 2 months. Sociodemographic and anthropometric characteristic was obtained; a blood sample was collected from the chosen patients and a biochemical test (uric acid, creatinine, urea, total cholesterol, high density lipoproteins cholesterol, triglyceride) was analyzed by spectrophotometric method. Statistical tests were carried out using SPSS statistical software. Logistic regression analyses identified factors associated with variables of interest. The significance was measured by a p < 0.05 with a confidential level of 95%. Results: The patient population was made up of 100 patients. The sex ratio was 1.22 in favor of men. The prevalence of hyperuricemia in our study was 28.0% with 31.1% in women and 27.3% in men. The mean average of uric acid in the hyperuricemia population was 7.50 ± 1.24 mg/L and the normal uricemia population was 4.69 ± 1.49 mg/L (p < 0.0001). The mean average triglyceride in the hyperuricemia population was 143 ± 14 and 117.55 ± 55.52 mg/dL in normal uricemia with p = 0.046. Age range [35-45] and hypertriglyceridemia have been associated with hyperuricemia with respectively (odds ratio [OR] = 4.07, p < 0.015) confidence interval, CI: [0.89: 97.0]) and ([OR = 2.50, p < 0.046] CI: [1.01: 6.09]). Conclusion: The prevalence of hyperuricemia was relatively high and has been associated with metabolic disorders in the population. It is necessary to focus on early diagnoses, treatment, and early intervention in view to prevent chronic diseases associated with hyperuricemia.

A Review of Cervidae Visual Ecology.

This review examines the visual systems of cervids in relation to their ability to meet their ecological needs and how their visual systems are specialized for particular tasks. Cervidae encompasses a diverse group of mammals that serve as important ecological drivers within their ecosystems. Despite evidence of highly specialized visual systems, a large portion of cervid research ignores or fails to consider the realities of cervid vision as it relates to their ecology. Failure to account for an animal's visual ecology during research can lead to unintentional biases and uninformed conclusions regarding the decision making and behaviors for a species or population. Our review addresses core behaviors and their interrelationship with cervid visual characteristics. Historically, the study of cervid visual characteristics has been restricted to specific areas of inquiry such as color vision and contains limited integration into broader ecological and behavioral research. The purpose of our review is to bridge these gaps by offering a comprehensive review of cervid visual ecology that emphasizes the interplay between the visual adaptations of cervids and their interactions with habitats and other species. Ultimately, a better understanding of cervid visual ecology allows researchers to gain deeper insights into their behavior and ecology, providing critical information for conservation and management efforts.

Influence of visual perception on movement decisions by an ungulate prey species.

Visual perception is dynamic and depends on physiological properties of a species' visual system and physical characteristics of the environment. White-tailed deer (Odocoileus virginianus) are most sensitive to short- and mid-wavelength light (e.g. blue and green). Wavelength enrichment varies spatially and temporally across the landscape. We assessed how the visual perception of deer influences their movement decisions. From August to September 2019, we recorded 10-min locations from 15 GPS-collared adult male deer in Central Florida. We used Hidden-Markov models to identify periods of movement by deer and subset these data into three time periods based on temporal changes in light environments. We modeled resource selection during movement using path-selection functions and simulated 10 available paths for every path used. We developed five a priori models and used 10-fold cross validation to assess our top model's performance for each time period. During the day, deer selected to move through woodland shade, avoided forest shade, and neither selected nor avoided small gaps. At twilight, deer avoided wetlands as cloud cover increased but neither selected nor avoided other cover types. Visual cues and signals are likely more conspicuous to deer in short-wavelength-enriched woodland shade during the day, while at twilight in long-wavelength-enriched wetlands during cloud cover, visual cues are likely less conspicuous. The nocturnal light environment did not influence resource selection and likely has little effect on deer movements because it's relatively homogenous. Our findings suggest visual perception relative to light environments is likely an underappreciated driver of behaviors and decision-making by an ungulate prey species.

Sheptide A: an antimalarial cyclic pentapeptide from a fungal strain in the Herpotrichiellaceae.

As part of ongoing efforts to isolate biologically active fungal metabolites, a cyclic pentapeptide, sheptide A (1), was discovered from strain MSX53339 (Herpotrichiellaceae). The structure and sequence of 1 were determined primarily by analysis of 2D NMR and HRMS/MS data, while the absolute configuration was assigned using a modified version of Marfey's method. In an in vitro assay for antimalarial potency, 1 displayed a pEC50 value of 5.75 ± 0.49 against malaria-causing Plasmodium falciparum. Compound 1 was also tested in a counter screen for general cytotoxicity against human hepatocellular carcinoma (HepG2), yielding a pCC50 value of 5.01 ± 0.45 and indicating a selectivity factor of ~6. This makes 1 the third known cyclic pentapeptide biosynthesized by fungi with antimalarial activity.

Dissociative experiences of adolescents with borderline personality disorder: description and prediction.

AIMS: The first purpose of this study was to assess the severity of dissociative experiences reported by adolescent inpatients with borderline personality disorder (BPD). The second purpose was to compare the severity of their dissociative symptoms to those reported by a sample of adult inpatients with BPD. The third purpose of this study was to assess a range of clinically meaningful predictors of the severity of dissociation in adolescents and adults with BPD. METHODS: The Dissociative Experiences Scale (DES) was administered to a total of 89 hospitalized girls and boys aged 13-17 with BPD and 290 adult inpatients with BPD. Predictors of the severity of dissociation in adolescents and adults with BPD were assessed using the Revised Childhood Experiences Questionnaire (a semi-structured interview), the NEO, and the SCID I. RESULTS: Borderline adolescents and adults had non-significant differences on their overall DES scores and subscale scores. They also had a non-significant distribution of low, moderate, and high scores. In terms of multivariate predictors, neither temperament nor childhood adversity was a significant predictor of the severity of dissociative symptoms in adolescents. However, co-occurring eating disorders were found in multivariate analyses to be the only bivariate predictor to significantly predict this outcome. In adults with BPD, however, both the severity of childhood sexual abuse and co-occurring PTSD were significantly related to the severity of dissociative symptoms in multivariate analyses. CONCLUSIONS: Taken together, the results of this study suggest that the severity of dissociation is not significantly different in adolescents and adults with BPD. However, the etiological factors differ substantially.

Genomic characterization of DICER1-associated neoplasms uncovers molecular classes.

DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated "low-grade mesenchymal tumor with DICER1 alteration" (LGMT DICER1), "sarcoma with DICER1 alteration" (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.

Well-differentiated Sertoli-Leydig Cell Tumors (SLCTs) Are Not Associated With DICER1 Pathogenic Variants and Represent a Different Tumor Type to Moderately and Poorly Differentiated SLCTs.

Sertoli-Leydig cell tumors (SLCTs) are uncommon ovarian sex cord-stromal neoplasms which are currently classified into well, moderately, and poorly differentiated and retiform types. Well-differentiated SLCT is the least common and typically occurs in pure form, whereas moderately and poorly differentiated and retiform types often comprise a morphologic spectrum with an admixture of all 3. DICER1 pathogenic variants are very common in SLCTs but, as far as we are aware, have not been reported in well-differentiated neoplasms, although the number of cases studied is small due to the rarity of this neoplasm. We undertook DICER1 molecular testing in a cohort of 18 well-differentiated SLCTs and show all these to be DICER1 wild-type. None of the cases harbored the p. FOXL2 C134W hotspot mutation. Based upon the DICER1 molecular results, together with morphologic observations, we propose that well-differentiated SLCT is an unrelated neoplasm to the more common moderately/poorly differentiated and retiform SLCTs and is a fundamentally distinct and unrelated tumor type within the ovarian sex cord-stromal tumor family. The implications for tumor nomenclature and recommendations for future tumor classification are discussed within the context of tumors collectively known as SLCTs.

Ovarian Signet-ring Stromal Tumor: A Morphologic, Immunohistochemical, and Molecular Study of 7 Cases With Discussion of the Differential Diagnosis.

Signet-ring stromal tumor (SRST) is a rare ovarian stromal neoplasm characterized by a population of bland signet-ring cells, devoid of mucin or lipid, in a generally cellular fibromatous stroma. Previous reports have described heterogenous immunohistochemical and molecular genetic findings, including occasional nuclear ß-catenin expression and/or CTNNB1 mutations. We report 10 ovarian stromal neoplasms originally diagnosed as SRST. All but 1 tumor underwent detailed immunohistochemical analysis (including ß-catenin) and 5 of 10 had CTNNB1 mutation analysis performed. All tumors contained a population of morphologically bland signet-ring cells that ranged from 15% to 95% of the neoplasm, characterized by a single large empty intracytoplasmic vacuole, mostly with nuclear indentation. Six of the 10 tumors contained cellular fibroma-like areas, comprising from 10% to 85% of the neoplasm. Three of the 10 tumors were reclassified as microcystic stromal tumor with signet-ring cells on the basis of the microcyst formation and hyalinized stroma, beta-catenin and cyclin D1 nuclear expression and/or CTNNB1 mutation, CD10 staining and largely absent expression of inhibin and calretinin. In the remaining 7 tumors, the diagnosis of SRST remained, constituting the largest series of SRST reported in the literature to date. The results of our study suggest that a subset of tumors diagnosed as ovarian SRST, especially those which show ß-catenin nuclear positivity and/or CTNNB1 mutation, likely represent microcystic stromal tumor with variant morphology. We also suggest that at least a subset of SRSTs without evidence of Wnt/ß-catenin pathway abnormalities may be related to ovarian fibromas. We discuss the differential diagnosis of ovarian neoplasms containing signet-ring cells.

Use of levodopa-carbidopa intestinal gel to treat patients with multiple system atrophy.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment for late-stage Parkinson's disease (PD) but had not been evaluated in levodopa-responsive patients with the parkinsonian variant of multiple system atrophy (MSA-P) and motor fluctuations. We aimed to assess the safety of LCIG in MSA-P patients. METHODS: In a retrospective, single-center study, we analyzed clinical and treatment-related data for all patients with MSA-P or PD treated with LCIG between December 2004 and November 2017. Adverse events (AEs) were classified into three classes: AEs related to gastrointestinal effects or to the PEG-J procedure, AEs related to the device, and AEs related to the pharmacological effect of LCIG. RESULTS: 7 MSA-P and 63 PD patients had been treated with LCIG for a median [interquartile range] period of 31 [16;43] and 19 [8;45] months, respectively. There were no significant intergroup differences in safety. Enteral nutrition was introduced at the same time as LCIG treatment in 4 (57%) MSA-P patients. In the MSA-P and PD groups, LCIG was associated with a better Global Clinical Impression score and discontinuation of oral anti-parkinsonian drugs (in 43% and 27% of cases, respectively). CONCLUSIONS: LCIG treatment is feasible in MSA-P patients with severe motor complications. The safety profile is similar to that seen in PD.

Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma.

With the widespread application of next-generation sequencing, the genetic landscape of uterine mesenchymal neoplasms has been evolving rapidly to include several recently identified fusion genes. Although chromosomal rearrangements involving the 10q22 and 17q21.31 loci have been reported in occasional uterine leiomyomas decades ago, the corresponding KAT6B::KANSL1 fusion has been only recently identified in 2 uterine tumors diagnosed as leiomyoma and leiomyosarcoma. We herein describe 13 uterine stromal neoplasms carrying a KAT6B::KANSL1 (n=11) and KAT6A::KANSL1 (n=2) fusion. Patient ages ranged from 33 to 81 years (median, 49 y). Tumor size was 2.6 to 23.5 cm (median, 8.2 cm). Nine tumors were myometrium-centered, and 3 had an intracavitary component. Original diagnoses were mostly low-grade endometrial stromal sarcoma (LG-ESS; 10 cases) with atypical features (limited CD10 expression, sex cord-like features, pericytic vasculature, and frequent myxoid changes). Treatment was hysterectomy±bilateral salpingo-oophorectomy (10), myomectomy (1), and curettage (2). Five patients were disease-free at 6 to 34 months, 3 (27%) died of disease at 2 to 47 months, and 3 were alive with disease at 2, 17, and 17 years. Histologically, most tumors showed variable overlap with LG-ESS, but they were generally well-circumscribed lacking the extensive permeative and angioinvasive growth typical of LG-ESS. They were composed of monotonous medium-sized oval and spindle cells arranged into diffuse sheets with prominent spiral-type arterioles and frequent pericytoma-like vascular pattern. Variable myxoid stromal changes were frequent. Mitotic activity ranged from 1 to >20 in 10 HPFs. Immunohistochemistry showed variable expression of CD10 (12/13), estrogen receptor (8/11), progesterone receptor (8/11), smooth muscle actin (9/11), desmin (4/12), h-caldesmon (2/10), calretinin (3/8), inhibin (1/7), WT1 (4/7), cyclin D1 (5/11; diffuse in only 1 case), and pankeratin (5/10). This series characterizes a KAT6B/A::KANSL1 fusion-positive uterine stromal neoplasm within the morphologic spectrum of LG-ESS but with atypical features. The relationship of these neoplasms to genuine LG-ESS remains unclear. This molecular subtype of uterine endometrial stromal sarcoma has the potential for an unfavorable clinical course despite the absence of widely invasive growth; nevertheless, analysis of more cases is necessary to delineate the phenotypic spectrum and biological potential of this tumor.

Ground State Properties of the Wide Band Gap Semiconductor Beryllium Sulfide (BeS).

We report the results from self-consistent calculations of electronic, transport, and bulk properties of beryllium sulfide (BeS) in the zinc-blende phase, and employed an ab-initio local density approximation (LDA) potential and the linear combination of atomic orbitals (LCAO). We obtained the ground state properties of zb-BeS with the Bagayoko, Zhao, and Williams (BZW) computational method, as enhanced by Ekuma and Franklin (BZW-EF). Our findings include the electronic energy bands, the total (DOS) and partial (pDOS) densities of states, electron and hole effective masses, the equilibrium lattice constant, and the bulk modulus. The calculated band structure clearly shows that zb-BeS has an indirect energy band gap of 5.436 eV, from Γ to a point between Γ and X, for an experimental lattice constant of 4.863 Å. This is in excellent agreement with the experiment, unlike the findings of more than 15 previous density functional theory (DFT) calculations that did not perform the generalized minimization of the energy functional, required by the second DFT theorem, which is inherent to the implementation of our BZW-EF method.

Attracting Diverse Students to Field Experiences Requires Adequate Pay, Flexibility, and Inclusion.

Access to field experiences can increase participation of diverse groups in the environmental and natural resources (ENR) workforce. Despite a growing interest among the ENR community to attract and retain diverse students, minimal data exist on what factors undergraduate students prioritize when applying for field experiences. Using a nationwide survey of US undergraduate ENR students, we show that attracting most students to field experiences-especially racial or ethnic minority students-will require pay above minimum wage. However, the concurrent landscape of pay in ENR fell short of meeting many students' pay needs. Aside from pay, ENR students valued training in technical field skills and analytical or research skills, working with their desired study species or taxa, and working near school or family. Additional barriers beyond limited pay included incompatible schedules and noninclusive work environments. Our findings provide important insights for attracting a diverse workforce to this critical stage in career advancement for students in ENR.

Mapping the cellular origin and early evolution of leukemia in Down syndrome.

Children with Down syndrome have a 150-fold increased risk of developing myeloid leukemia, but the mechanism of predisposition is unclear. Because Down syndrome leukemogenesis initiates during fetal development, we characterized the cellular and developmental context of preleukemic initiation and leukemic progression using gene editing in human disomic and trisomic fetal hematopoietic cells and xenotransplantation. GATA binding protein 1 (GATA1) mutations caused transient preleukemia when introduced into trisomy 21 long-term hematopoietic stem cells, where a subset of chromosome 21 microRNAs affected predisposition to preleukemia. By contrast, progression to leukemia was independent of trisomy 21 and originated in various stem and progenitor cells through additional mutations in cohesin genes. CD117+/KIT proto-oncogene (KIT) cells mediated the propagation of preleukemia and leukemia, and KIT inhibition targeted preleukemic stem cells.

Maximizing cancer prevention through genetic navigation for Lynch syndrome detection in women with newly diagnosed endometrial and nonserous/nonmucinous epithelial ovarian cancer.

BACKGROUND: Despite recommendations for reflex immunohistochemistry (IHC) for mismatch repair (MMR) proteins to identify Lynch syndrome (LS), the uptake of genetic assessment by those who meet referral criteria is low. The authors implemented a comprehensive genetic navigation program to increase the uptake of genetic testing for LS in patients with endometrial cancer (EC) or nonserous/nonmucinous ovarian cancer (OC). METHODS: Participants with newly diagnosed EC or OC were prospectively recruited from 3 cancer centers in Ontario, Canada. Family history questionnaires were used to assess LS-specific family history. Reflex IHC for MMR proteins was performed with the inclusion of clinical directives in pathology reports. A trained genetic navigator initiated a genetic referral on behalf of the treating physician and facilitated genetic referrals to the closest genetics center. RESULTS: A total of 841 participants (642 with EC, 172 with OC, and 27 with synchronous EC/OC) consented to the study; 194 (23%) were MMR-deficient by IHC. Overall, 170 women (20%) were eligible for a genetic assessment for LS: 35 on the basis of their family history alone, 24 on the basis of their family history and IHC, 82 on the basis of IHC alone, and 29 on the basis of clinical discretion. After adjustments for participants who died (n = 6), 149 of 164 patients (91%) completed a genetic assessment, and 111 were offered and completed genetic testing. Thirty-four women (4.0% of the total cohort and 30.6% of those with genetic testing) were diagnosed with LS: 5 with mutL homolog 1 (MLH1), 9 with mutS homolog 2 (MSH2), 15 with mutS homolog 6 (MSH6), and 5 with PMS2. CONCLUSIONS: The introduction of a navigated genetic program resulted in a high rate of genetic assessment (>90%) in patients with gynecologic cancer at risk for LS.

Endometrial Stem/Progenitor cell (ES/PC) Marker Expression Profile in Adenosarcoma and Endometrial Stromal Sarcoma.

BACKGROUND: The uterus is one of the most dynamic organs in the human body, and this dynamic homeostasis is supported by endometrial stem/progenitor cells (ES/PCs), which are heterogeneous in their phenotype and degree of differentiation. ES/PCs are generally localized in the endometrial stroma, the site of origin for adenosarcoma and endometrial stromal sarcoma (ESS). Subsets of ESSs and adenosarcomas harbor SUZ12 or DICER1 gene alterations, two genes with roles in embryonic stem cell biology. However, the possible contribution of ES/PCs to tumorigenesis is unexplored. METHOD: We examined the expression of eleven ES/PC markers, along with three proteins expressed in the mature endometrial stroma (ER, PR and CD10) in 60 uterine tumors (24 low-, 11 high-grade ESS, 25 adenosarcomas). Protein expression profiles were assessed by unsupervised hierarchical clustering. miRNA expression profiles were examined in a subset of adenosarcoma with/without DICER1 mutations, using the NanoString platform. RESULTS: ES/PC markers were variably expressed, and the tumors exhibited limited immunophenotypic resemblance to different ES/PCs. Within the ESSs, the ES/PC marker clustering pattern was prognostic for both overall and disease-free survival. Comparing adenosarcomas and ESSs, most high-grade ESSs clustered with one another, while low-grade ESSs and adenosarcomas tended to cluster with one another. Among the adenosarcomas, the miRNA expression profiles were varied with respect to the DICER1 mutation status, with pathway analysis pointing to dysregulated signal transduction and stem cell biology. CONCLUSIONS: ESSs and adenosarcomas exhibit varying immunophenotypic resemblance to ES/PCs. These expression profiles have prognostic implications and may be genetically driven.

Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysis.

BACKGROUND: Endometrial cancers (ECs) with somatic mutations in DNA polymerase epsilon (POLE) are characterized by unfavorable pathological features, which prompt adjuvant treatment. Paradoxically, women with POLE-mutated EC have outstanding clinical outcomes, and this raises concerns of overtreatment. The authors investigated whether favorable outcomes were independent of treatment. METHODS: A PubMed search for POLE and endometrial was restricted to articles published between March 1, 2012, and March 1, 2018, that provided individual patient data (IPD), adjuvant treatment, and survival. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines for IPD, the authors used univariate and multivariate one-stage meta-analyses with mixed effects Cox models (random effects for study cohorts) to infer the associations of treatment, traditional prognostic factors, and outcome, which was defined as the time from first diagnosis to any adverse event (progression/recurrence or death from EC). RESULTS: Three hundred fifty-nine women with POLE-mutated EC were identified; 294 (82%) had pathogenic mutations. Worse outcomes were demonstrated in patients with nonpathogenic POLE mutations (hazard ratio, 3.42; 95% confidence interval, 1.47-7.58; log-rank P < .01). Except for stage (P < .01), traditional prognosticators were not associated with progression/recurrence or death from disease. Adverse events were rare (11 progressions/recurrences and 3 disease-specific deaths). Salvage rates in patients who experienced recurrence were high and sustained, with 8 of 11 alive without evidence of disease (range, 5.5-14.2 years). Adjuvant treatment was not associated with outcome. CONCLUSIONS: Clinical outcomes for ECs with pathogenic POLE mutations are not associated with most traditional risk parameters, and patients do not appear to benefit from adjuvant therapy. The observed low rates of recurrence/progression and the high and sustained salvage rates raise the possibility of safely de-escalating treatment for these patients. LAY SUMMARY: Ten percent of all endometrial cancers have mutations in the DNA repair gene DNA polymerase epsilon (POLE). Women who have endometrial cancers with true POLE mutations experience almost no recurrences or deaths from their cancer even when their tumors appear to have very unfavorable characteristics. Additional therapy (radiation and chemotherapy) does not appear to improve outcomes for women with POLE-mutated endometrial cancer, and this supports the move to less therapy and less associated toxicity. Diligent classification of endometrial cancers by molecular features provides valuable information to inform prognosis and to direct treatment/no treatment.

Symptomatic Disorders in Adults and Adolescents With Borderline Personality Disorder.

Symptomatic disorders often co-occur with borderline personality disorder (BPD). This study's purpose was to compare the rates of comorbidity reported by adult and adolescent inpatients with BPD, including complex comorbidity (i.e., a combination of disorders of affect and impulsivity). One hundred four adolescents (aged 13-17) and 290 adults (aged 18-35) with BPD were interviewed using an age-appropriate semistructured interview for the assessment of symptomatic disorders. Lifetime rates of mood disorders and ADHD were quite similar for the two study groups. However, rates of anxiety disorders, including PTSD, substance use disorders, eating disorders, and complex comorbidity were significantly higher among adults than adolescents. Taken together, the results of this study suggest that broadly defined disorders of both affect and impulsivity are more common among adults than adolescents with BPD. They also suggest that a pattern of complex comorbidity is even more distinguishing for these two groups of borderline patients.

Affective and Behavioral Characteristics of Adolescent and Adult Borderline Personality Disorder.

Adults with borderline personality disorder (BPD) report greater affective lability, impulsivity, and aggression compared to same-age peers, but no studies have examined whether these findings are replicable among adolescents with BPD and their peers, or whether adolescents and adults with BPD report symptoms of comparable severity. One hundred and one adolescent (age 13-17) BPD inpatients and 60 age-matched, psychiatrically healthy adolescents completed self-report measures for affective lability, impulsivity, and aggression. Comparison samples included 29 and 41 adult outpatients with BPD and 127 community adults with BPD. Adolescents with BPD reported greater severity of all symptoms except nonplanning impulsiveness compared to peers. They reported similar symptom severity to adults but reported less severe verbal aggression and anger. Adolescents with BPD are distinguishable from typically developing adolescents on self-reported, dimensional affective and behavioral symptom measures, and may experience these symptoms at comparable severity to adult counterparts.