tbuckley/cabot-search huggingface dataset:
Germline structural variation globally impacts the cancer transcriptome including disease-relevant genes
Authors: Fengju Chen, Yiqun Zhang, Fritz J. Sedlazeck, Chad J. Creighton
Journal: Cell Reports Medicine (2024)

Germline variation and somatic alterations contribute to the molecular profile of cancers. We combine RNA with whole genome sequencing across 1,218 cancer patients to determine the extent germline structural variants (SVs) impact expression of nearby genes. For hundreds of genes, recurrent and common germline SV breakpoints within 100 kb associate with increased or decreased expression in tumors spanning various tissues of origin. A significant fraction of germline SV expression associations involves duplication of intergenic enhancers or 3′ UTR disruption. Genes altered by both somatic and germline SVs include ATRX and CEBPA. Genes essential in cancer cell lines include BARD1 and IRS2. Genes with both expression and germline SV breakpoint patterns associated with patient survival include GCLM. Our results capture a class of phenotypic variation at work in the disease setting, including genes with cancer roles. Specific germline SVs represent potential cancer risk variants for genetic testing, including those involving genes with targeting implications.
Bile acid profiling as an effective biomarker for staging in pediatric inflammatory bowel disease
Authors: Wei Chen, Daosheng Wang, Xing Deng, Hong Zhang, Danfeng Dong, Tongxuan Su, Qiuya Lu, Cen Jiang, Qi Ni, Yingchao Cui, Qianli Zhao, Xuefeng Wang, Yuan Xiao, Yibing Peng
Journal: Gut Microbes (2024)

Rapid and accurate clinical staging of pediatric patients with inflammatory bowel disease (IBD) is crucial to determine the appropriate therapeutic approach. This study aimed to identify effective, convenient biomarkers for staging IBD in pediatric patients. We recruited cohorts of pediatric patients with varying severities of IBD to compare the features of the intestinal microbiota and metabolites between the active and remitting disease stages. Metabolites with potential for staging were targeted for further assessment in both patients and colitis model mice. The performance of these markers was determined using machine learning and was validated in a separate patient cohort. Pediatric patients with IBD exhibited distinct gut microbiota structures at different stages of disease activity. The enterotypes of patients with remitting and active disease were Bacteroides-dominant and Escherichia-Shigella-dominant, respectively. The bile secretion pathway showed the most significant differences between the two stages. Fecal and serum bile acid (BA) levels were strongly related to disease activity in both children and mice. The ratio of primary BAs to secondary BAs in serum was developed as a novel comprehensive index, showing excellent diagnostic performance in stratifying IBD activity (0.84 area under the receiver operating characteristic curve in the primary cohort; 77% accuracy in the validation cohort). In conclusion, we report profound insights into the interactions between the gut microbiota and metabolites in pediatric IBD. Serum BAs have potential as biomarkers for classifying disease activity, and may facilitate the personalization of treatment for IBD.
Coma Prognostication After Acute Brain Injury
Authors: David Fischer, Brian L. Edlow
Journal: JAMA Neurology (2024)

Importance Among the most impactful neurologic assessments is that of neuroprognostication, defined here as the prediction of neurologic recovery from disorders of consciousness caused by severe, acute brain injury. Across a range of brain injury etiologies, these determinations often dictate whether life-sustaining treatment is continued or withdrawn; thus, they have major implications for morbidity, mortality, and health care costs. Neuroprognostication relies on a diverse array of tests, including behavioral, radiologic, physiological, and serologic markers, that evaluate the brain’s functional and structural integrity. Observations Prognostic markers, such as the neurologic examination, electroencephalography, and conventional computed tomography and magnetic resonance imaging (MRI), have been foundational in assessing a patient’s current level of consciousness and capacity for recovery. Emerging techniques, such as functional MRI, diffusion MRI, and advanced forms of electroencephalography, provide new ways of evaluating the brain, leading to evolving schemes for characterizing neurologic function and novel methods for predicting recovery. Conclusions and Relevance Neuroprognostic markers are rapidly evolving as new ways of assessing the brain’s structural and functional integrity after brain injury are discovered. Many of these techniques remain in development, and further research is needed to optimize their prognostic utility. However, even as such efforts are underway, a series of promising findings coupled with the imperfect predictive value of conventional prognostic markers and the high stakes of these assessments have prompted clinical guidelines to endorse emerging techniques for neuroprognostication. Thus, clinicians have been thrust into an uncertain predicament in which emerging techniques are not yet perfected but too promising to ignore. This review illustrates the current, and likely future, landscapes of prognostic markers. No matter how much prognostic markers evolve and improve, these assessments must be approached with humility and individualized to reflect each patient’s values.
A Patient With Oral Discomfort and Reduced Oral Aperture
Authors: Gloria F. Chen, Simon F. Roy, Jeffrey M. Cohen
Journal: JAMA (2024)

A patient had burning and pain in the mouth, reduced oral aperture, white-tan plaques on the oral mucosa, and thickened buccal mucosae bilaterally; biopsy of the lower labial mucosa showed subepithelial fibrosis. She had no history of cigarette smoking or use of chewing tobacco but had current and past history of chewing areca nuts. What is the diagnosis and what would you do next?
Changes to Sexual Identity Response Options in the Youth Risk Behavior Survey
Authors: Gregory L. Phillips, Michael G. Curtis, Scar Winter Kelsey, Ysabel Beatrice Floresca, Shahin Davoudpour, Kagen Quiballo, Lauren B. Beach
Journal: JAMA Pediatrics (2024)

This survey study discusses changes in the proportion of youths who selected “not sure” among other response options to questions about their sexual identity in the National Youth Risk Behavior Survey between 2019 and 2021 and recommends measures to inclusively reflect sexual identities.
The Real Impact of the Alabama Supreme Court Decision in <i>LePage v Center for Reproductive Medicine</i>
Authors: Michelle J. Bayefsky, Arthur L. Caplan, Gwendolyn P. Quinn
Journal: JAMA (2024)

This Viewpoint breaks down the myriad ways the Alabama Supreme Court decision to declare frozen embryos as legal equivalents to children harms the health of mothers and fetuses, limits reproductive decision-making based on genetics and out-of-reach costs, and impedes research.
Abstract B048: Evaluating the impact of pulmonary diseases on the use of microRNAs as biomarkers for early detection of ovarian cancer
Authors: Monica Moore, Laura Wollborn, Sudhanshu Mishra, James Webber, Kevin M. Elias
Journal: Cancer Research (2024)

Abstract Background: Efforts are ongoing to develop new biomarkers to diagnose ovarian cancer at earlier, more curable stages. microRNAs (miRNAs) have emerged as a promising new class of circulating biomarkers for ovarian cancer diagnosis and prognosis. As other biomarkers, such as CA-125, are non-specifically elevated in pulmonary diseases, evaluating how miRNA expression is affected by various lung conditions will inform the interpretation of miRNAs as a potential clinical test. Asthma and bronchitis are of particular interest because miRNA expression in the lung is markedly affected by environmental respiratory irritants such as cigarette smoke and air pollution. Moreover, as the burden of asthma and bronchitis in the United States falls disproportionately on minority communities, so a test confounded by asthma might be less generalizable to a diverse patient population. Methods: Serum samples from 1,614 women enrolled in the Mass General Brigham Biobank were analyzed for miRNAs using a focused panel of 179 miRNA Fireplex® probes optimized for serum profiling. In addition to the miRNA data, electronic health records were reviewed to pair the biomarker data with demographics such as age, race, ethnicity, zip code, reproductive health histories, and comorbidities, including pulmonary diseases like asthma/bronchitis. miRNAs associated with pulmonary diseases were identified by univariate analysis, adjusting for multiple comparisons using Bonferroni correction. Results: The analysis compared the circulating miRNA profiles of 446 asthma/bronchitis subjects vs. 1168 non-asthma/non-bronchitis subjects. Among the miRNAs examined, there was only one miRNA, miR-133a-3p, that showed a significant difference between the two groups. We further focused on 8 specific miRNAs that have been proposed as diagnostic biomarkers for ovarian cancer and found no significant difference in expression between asthma/bronchitis subjects vs. non-asthma/non-bronchitis subjects.Conclusion: Asthma and bronchitis do not significantly confound measurements of miRNAs that are potential biomarkers for ovarian cancer. This further supports miRNAs as biomarkers for early detection of ovarian cancer and suggests that miRNAs are likely to generalize well if deployed as part of a screening test among the general population. Citation Format: Monica Moore, Laura Wollborn, Sudhanshu Mishra, James Webber, Kevin M. Elias. Evaluating the impact of pulmonary diseases on the use of microRNAs as biomarkers for early detection of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B048.
Enhancing Quality and Safety in Critical Care—Challenges and Strategies for Central Venous Catheters
Authors: Elie A. Saade, Francis T. Lytle, Peter J. Pronovost
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Development and Validation of an Automated Classifier to Diagnose Acute Otitis Media in Children
Authors: Nader Shaikh, Shannon J. Conway, Jelena Kovačević, Filipe Condessa, Timothy R. Shope, Mary Ann Haralam, Catherine Campese, Matthew C. Lee, Tomas Larsson, Zafer Cavdar, Alejandro Hoberman
Journal: JAMA Pediatrics (2024)

Acute otitis media (AOM) is a frequently diagnosed illness in children, yet the accuracy of diagnosis has been consistently low. Multiple neural networks have been developed to recognize the presence of AOM with limited clinical application.
Reidentification With Birth-Registered Sex in a Western Australian Pediatric Gender Clinic Cohort
Authors: Blake S. Cavve, Xander Bickendorf, Jack Ball, Liz A. Saunders, Cati S. Thomas, Penelope Strauss, Georgia Chaplyn, Larissa Marion, Aris Siafarikas, Uma Ganti, Aaron Wiggins, Ashleigh Lin, Julia K. Moore
Journal: JAMA Pediatrics (2024)

Some young people who identify as transgender and seek gender-affirming medical care subsequently reidentify with their sex registered at birth. Evidence regarding the frequency and characteristics of this experience is lacking.
Abstract B108: Zinc finger protein 217 (ZNF217) promotes ovarian cancer metastasis through interaction with estrogen
Authors: Kathryn Wardrup, Achuth Padmanabhan
Journal: Cancer Research (2024)

Abstract ZNF217 is a transcription factor located at chromosomal region 20q13.2 which is frequently amplified in many human cancers, including ovarian. Consistently, ZNF217 mRNA is overexpressed in epithelial ovarian cancer and is negatively correlated with 5-year survival predictions. Despite this connection, little is known about the role of ZNF217 in the development of epithelial ovarian cancer. To explore the role of ZNF217 in this context, we generated ovarian cancer cell lines that stably overexpress ZNF217 to prolife in vitro pro-metastatic phenotypes. We found that increased expression of ZNF217 led to increases in cell proliferation, cell migration, adhesion, and transwell invasion. Subsequent gene expression analysis revealed alterations consistent with the induction of epithelial to mesenchymal transition (EMT). Depleting ZNF217 resulted in abrogation of these phenotypes. Consistent with these in vitro data, both intraperitoneal and ovary intrabursal xenograft models demonstrated that increased levels of ZNF217 rapidly enhanced the rate of tumorigenesis in vivo. RNA sequencing analyses revealed significant alterations in expression of genes involved in estrogen signaling, such as ESR1 and ESR2. We found that in vitro the presence of 17β-estradiol synergistically increased cell proliferation and invasion when compared to cells in media lacking estrogens. In vivo, ovariectomized mice supplemented with a subcutaneous slow release 17β-estradiol tablet in combination with high-ZNF217 expressing cells displayed an increased rate of tumorigenesis and an increase in disease severity as compared to controls lacking estrogens. The findings reveal a novel transcription factor that is key in promoting ovarian cancer progression and metastasis and highlights a functional role for estrogen in promoting ZNF217-driven metastasis. Citation Format: Kathryn Wardrup, Achuth Padmanabhan. Zinc finger protein 217 (ZNF217) promotes ovarian cancer metastasis through interaction with estrogen [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B108.
Socioeconomic Status and Overall Survival Among Patients With Hematological Malignant Neoplasms
Authors: Lars Hernández Nielsen, Daniel Tuyet Kristensen, Lasse Hjort Jakobsen, Martin Bøgsted, Henrik Gregersen, Jakob Madsen, Marianne Tang Severinsen, Rasmus Froberg Brøndum
Journal: JAMA Network Open (2024)

Importance In recent years, there has been a focus on reducing the socioeconomic gap in survival for hematological malignant neoplasms. Understanding recent developments is important to develop further intervention to improve care. Objective To investigate the temporal trend in associations of socioeconomic status (SES) with survival among 3 aggressive hematological malignant neoplasms: multiple myeloma (MM), acute myeloid leukemia (AML), and diffuse large B-cell lymphoma (DLBCL). Design, Setting, and Participants This nationwide, population-based cohort study used retrospectively collected data from 3 clinical registries of patients diagnosed in Denmark between January 1, 2005, and December 31, 2020, with follow-up until December 31, 2021. Analyses were stratified by diagnosis year (2005-2009, 2010-2014, and 2015-2020). Participants were patients aged 25 to 65 years with hematological malignant neoplasms. Patients with missing data on education were excluded. Data were analyzed from October 14, 2022, to January 2, 2024. Exposure Education was used as a proxy for SES and defined low- and high-SES groups based on the completion of tertiary education. Main Outcomes and Measures The main outcome was overall survival (OS), analyzed using Kaplan-Meier (log rank) method and Cox proportional hazards regression adjusted for age, sex, performance status, comorbidities, and disease-specific prognostic indices. Two-year OS through time and survival difference were estimated using flexible parametric survival models. Results A total of 5677 patients (median [IQR] age, 58 [51-62] years; 3177 [57.0%] male) were assessed, including 1826 patients with MM, 1236 patients with AML, and 2509 patients with DLBCL. The 2-year OS increased over time for patients with MM (78.8% [95% CI, 75.4%-82.3%] to 91.4% [95% CI, 89.3%-93.5%]), AML (42.2% [95% CI, 37.8%-47.1%] to 52.7% [95% CI, 48.0%-57.9%]), and DLBCL (80.1% [95% CI, 77.4%-82.8%] to 88.1% [95% CI, 86.0%-90.3%]). For MM and DLBCL, no association of SES with survival was observed after adjustment (MM: hazard ratio [HR], 0.99 [95% CI, 0.85-1.15]; DLBCL: HR, 1.08 [95% CI, 0.91-1.29]). For AML, a negative association was observed between low SES and survival (HR, 1.49 [95% CI, 1.25-1.76]), but the association was attenuated in recent years. The difference in hazard for patients with low SES and AML was observed in the first 2 years after diagnosis. Conclusions and Relevance These findings suggest that survival has improved among patients with these hematological malignant neoplasms. While patients with MM and DLBCL had increased survival in all groups, disparities were observed in AML outcomes, primarily in the first years after diagnosis. These results suggest that differences originate in factors specific to AML.
Abstract PR-008: Follicular fluid aids in cell adhesion, spreading and shows an age-dependent effect on DNA damage in fallopian tube epithelial cells
Authors: Amrita Salvi, Wenping Li, Stephanie M. Cologna, Mary Ellen Pavone, Francesca E. Duncan, Joanna E. Burdette
Journal: Cancer Research (2024)

Abstract Ovarian cancer is the 5th leading cause of cancer related death in women with a low 5-year survival rate. Ovarian cancer is rarely detected early, and likely arises from the fimbriated end of the fallopian tube epithelium (FTE). There is a correlation between ovarian cancer and ovulation whereby ovulation suppression through use of oral contraception or pregnancy reduces the risk of ovarian cancer. Despite the association of ovarian cancer with ovulation, due to the lack of early detection methods, the disease typically presents as late stage, metastatic cancer in post-menopausal women who are no longer ovulating. The goal of this study was to understand how ovulation and the process of aging interact to provide a permissive environment for ovarian cancer initiation and progression in the FTE. The process of ovulation releases follicular fluid and induces the DNA damage response pathway in the FTE, but the role of aging on FTE exposure to follicular fluid has not been tested. De-identified follicular fluid samples were collected from 14 women (7 reproductively young (29-35 years) and 7 reproductively aged (40-44 years)) undergoing ART (Assisted Reproductive Technology) through the Northwestern University Reproductive Tissue Library (NU-RTL). We found that follicular fluid caused DNA damage and lipid oxidation in an age-dependent manner and cell proliferation in a dose-dependent manner in FTE cells. Interestingly, follicular fluid disrupted FTE spheroid formation and instead stimulated attachment and growth on ultra-low attachment plates. Follicular fluid when coated on the surface of the ultra-low plates enhanced FTE cell adhesion, spreading and proliferation. Proteomics analysis of the follicular fluid identified vitronectin, a glycoprotein as the factor responsible for FTE cell attachment and spreading. Overall, this study demonstrated that aging contributed to lipid oxidation and DNA damage of FTE cells and identified vitronectin in the follicular fluid as a protein factor that facilitates FTE cells to detach from 3D spheroids and spread on low attachment surfaces. Citation Format: Amrita Salvi, Wenping Li, Stephanie M. Cologna, Mary Ellen Pavone, Francesca E. Duncan, Joanna E. Burdette. Follicular fluid aids in cell adhesion, spreading and shows an age-dependent effect on DNA damage in fallopian tube epithelial cells [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr PR-008.
Abstract B056: The unconfounded effect of bevacizumab on advanced ovarian clear cell carcinoma: a systematic review, traditional meta-analysis, and network meta-analysis
Authors: Fisher Kuan-Ju Huang
Journal: Cancer Research (2024)

Abstract Background Ovarian clear cell carcinoma (OCCC) accounts for 5-20% of all epithelail ovarian cancers, and is associated high recurrence rate and chemoresistance. There are some new therapies available in recent years, including bevacizumab, an anti-VEGF monoclonal antibody, and the poly ADP-ribose polymerase (PARP) inhibitors. Previous research and current support the use of both medication in OCCC. However, most of the studies reported results for all subtypes collectively in which OCCC only accounted for a small proportion of the study cohort. Besides, dislike the high-grade serous subtype, only around 10% of OCCC respond to poly ADP-ribose polymerase (PARP) inhibitor. In the subgroup analysis from ICON7, Bevacizumab had limited role in OCCC patients, in which OCCC of any stage were included. On the other hand, another 2 multi-center studies evaluated Bevacizumab as the front-line or salvage therapy revealed positive results. However, the results could be biased due to unadjusted confounders. Objective: To find the real effect of Bevacizumab on advanced stage OCCC. Materials and Methods: A systematic review via searching the Pubmed with "ovarian clear cell carcinoma" and "bevacizumab" was performed. Any comparative study met the inclusion criteria. The data were extracted, evaluated and classified by their combination of potential confounders. Primary data from National Taiwan University Hospital (NTUH) Database were collected and incorporated into the traditional meta-analysis, and the network meta-analysis. The potential confounders for analysis include "residual tumor", "FIGO stage", and "functional status". Results: There were 3 retrospective studies, including one single-center study from Japan (N=28), one multi-center study from Japan (N=145), and one multi-center study from Korea (N=138). There were 64 patients identified from NTUH database between 2011 and 2020. By traditional meta-analysis, it revealed Bevacizumab is associated with improved progression-free survival (HR 0.62, 95% C.I. 0.44 - 0.87, common effect model, I2= 50%). After adjusted for confonders and analyzed by network meta-analysis, however, only "no residual tumor" is associated with improved progression-free survival (HR 0.37, 95% C.I. 0.14 - 0.97). The role of Bevacizumab on OCCC is limited (HR 1.20, 95% C.I. 0.51 - 2.83). Conclusion: By adjusting for possible confounders in published studies, it reveals that Bevacizumab may not improve progression-free survival in advanced-stage OCCC from a network meta-analysis. Citation Format: Fisher Kuan-Ju Huang. The unconfounded effect of bevacizumab on advanced ovarian clear cell carcinoma: a systematic review, traditional meta-analysis, and network meta-analysis [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B056.