tbuckley/cabot-search huggingface dataset:
CSIG-01. IDENTIFICATION OF PATHOGENESIS-RELEVANT microRNAs IN BRAIN METASTASIS
Authors: Elizabeth Mulcahy, Rossymar Colon, Ying Zhang, Myron Gibert, Jungeun Kim, Eric Devairakkam, Roger Abounader, Camilo Fadul
Journal: Neuro-Oncology (2020)

Abstract When brain metastasis develops, the prognosis of cancer is dismal. Insights into the biology of the primary cancer and the brain metastasis are necessary to inform more effective and targeted treatments. To study the role of microRNAs in brain metastasis, we performed differential expression profiling of 12 primary tumors and their paired brain metastases using smRNAseq (the 12 primary tumors included three non-small cell carcinomas, three melanomas, three endometrial carcinomas, one breast carcinoma, one thyroid carcinoma and one renal-cell carcinoma). To start, we identified microRNAs that were either highly upregulated or downregulated in the brain metastasis samples as compared to the paired primary tumors. After confirmation with real-time quantitative PCR, we further investigated the top microRNAs from both groups through functional assays performed in cell lines generated from primary melanoma, melanoma lymph node metastasis, and melanoma brain metastasis. From this top-down, patient sample to model cell-line approach we identified two microRNAs that are potentially important regulators in the development of brain metastasis. Characterization of their targets and their interactions may offer a therapeutic opportunity to improve the prognosis of patients with brain metastasis.
Assessment of Prevalence and Cost of Care Cascades After Routine Testing During the Medicare Annual Wellness Visit
Authors: Ishani Ganguli, Claire Lupo, Alexander J. Mainor, Qianfei Wang, E. John Orav, Meredith B. Rosenthal, Thomas D. Sequist, Carrie H. Colla
Journal: JAMA Network Open (2020)

<h3>Importance</h3> For healthy adults, routine testing during annual check-ups is considered low value and may trigger cascades of medical services of unclear benefit. It is unknown how often routine tests are performed during Medicare annual wellness visits (AWVs) or whether they are associated with cascades of care. <h3>Objective</h3> To estimate the prevalence of routine electrocardiograms (ECGs), urinalyses, and thyrotropin tests and of cascades (further tests, procedures, visits, hospitalizations, and new diagnoses) that might follow among healthy adults receiving AWVs. <h3>Design, Setting, and Participants</h3> Observational cohort study using fee-for-service Medicare claims data from beneficiaries aged 66 years and older who were continuously enrolled in fee-for-service Medicare between January 1, 2013, and March 31, 2015; received an AWV in 2014; had no test-relevant prior conditions; did not receive 1 of the 3 tests in the 6 months before the AWV; and had no test-relevant symptoms or conditions in the AWV testing period. Data were analyzed from February 13, 2019, to June 8, 2020. <h3>Exposure</h3> Receipt of a given test within 1 week before or after the AWV. <h3>Main Outcomes and Measures</h3> Prevalence of routine tests during AWVs and cascade-attributable event rates and associated spending in the 90 days following the AWV test period. Patient, clinician, and area-level characteristics associated with receiving routine tests were also assessed. <h3>Results</h3> Among 75 275 AWV recipients (mean [SD] age, 72.6 [6.1] years; 48 107 [63.9%] women), 18.6% (14 017) received at least 1 low-value test including an ECG (7.2% [5421]), urinalysis (10.0% [7515]), or thyrotropin test (8.7% [6534]). Patients were more likely to receive a low-value test if they were younger (adjusted odds ratio [aOR], 1.69 for ages 66-74 years vs ages ≥85 years [95% CI, 1.53-1.86]), White (aOR, 1.32 compared with Black [95% CI, 1.16-1.49]), lived in urban areas (aOR, 1.29 vs rural [95% CI, 1.15-1.46]), and lived in high-income areas (aOR, 1.26 for &gt;400% of the federal poverty level vs &lt;200% of the federal poverty level [95% CI, 1.16-1.37]). A total of 6.1 (95% CI, 4.8-7.5) cascade-attributable events per 100 beneficiaries occurred in the 90 days following routine ECGs and 5.4 (95% CI, 4.2-6.5) following urinalyses, with cascade-attributable cost per beneficiary of $9.62 (95% CI, $6.43-$12.80) and $7.46 (95% CI, $5.11-$9.81), respectively. No cascade-attributable events or costs were found to be associated with thyrotropin tests. <h3>Conclusions and Relevance</h3> In this study, 19% of healthy Medicare beneficiaries received routine low-value ECGs, urinalyses, or thyrotropin tests during their AWVs, more often those who were younger, White, and lived in urban, high-income areas. ECGs and urinalyses were associated with cascades of modest but notable cost.
CTNI-03. IMAGING FEATURES OF LEPTOMENINGEAL METASTASES OF NON-SMALL CELL LUNG CANCER: A SINGLE-CENTER REAL-WORLD STUDY
Authors: Junjie Zhen, Lei Wen, Shaoqun Li, Mingyao Lai, Changguo Shan, Linbo Cai
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND According to EANO-ESMO clinical practice guidelines, the MRI findings of LM are divided into 4 types, namely linear enhancement (type A), nodular enhancement (type B), linear combined with nodular enhancement (type C), and sign of hydrocephalus (type D). METHODS The MRI features of brain and spinal cord in patients diagnosed with NSCLC-LM in Guangdong Sanjiu Brain Hospital from 2010 until 2019 were investigated, and then were classified into 4 types. The imaging features were analyzed. RESULTS A total of 80 patients were enrolled in the study. The median age of the patients was 53.5 years old, and the median time from the initial diagnosis to the confirmed diagnosis of LM was 11.6 months. The results of enhanced MRI examination of the brain in 79 cases showed that the number of cases with enhancements of type A, B, C and D were 50 (63.3%), 0, 26 (32.9%) and 3 (3.8%), respectively, and that LM with metastases to the brain parenchyma was found in 42 cases (53.2%). The results of enhanced MRI examination of spinal cord in 59 cases showed that there were only enhancements of type A and C in 40 cases (67.8%) and 3 cases (5.0%), and no enhancement sign in the other 16 cases (27.2%). CONCLUSION MRI examination of brain and spinal cord will improve the detection rate of LM. The MRI features of NSCLC-LM in real world are mainly characterized by the linear enhancements of brain and spinal cord, followed by linear combined with nodular enhancement. The enhancements of type B and type D are rare in clinic. Almost half of the patients have LM and metastases to the brain parenchyma. Therefore, the differentiation of tumor metastases is needed to be paid attention to for the early diagnosis and the formulation of reasonable treatment plans.
NCOG-66. IMPLICATION OF D-DIMER IN THE DETECTION OF DEEP VENOUS THROMBOSIS (DVT) /PULMONARY EMBOLISM (PE) IN HIGH GRADE GLIOMA PATIENTS WITHOUT CLASSIC SYMPTOMS OF DVT/PE ON OR OFF AVASTIN TREATMENT
Authors: Ruchika Jha, Tulika Ranjan, Alexander Yu, Rodney Wegner, Stephen Karlovits
Journal: Neuro-Oncology (2020)

Abstract The incidence of DVT/PE in high grade glioma patients is very high with increased risk of intracranial hemorrhage (ICH) in patients with recent surgery, Avastin and chemotherapy induced thrombocytopenia. We have frequently encountered patients with PE who presented with increased fatigue and somnolence before they developed classic symptoms of PE. It is critical that a high index of suspicion be maintained and patient screened for early detection of PE. A retrospective chart review from June 2015 to May 2020 is being performed on 500 patients with high grade glioma. D-Dimer was used as a screening test for early detection of DVT/PE. Of the 175 patients analyzed 57(32.5 %) patients had DVT/PE, 12 had DVT only and 45 patients had PE with or without DVT. Fatigue which was out of proportion to the expected chemotherapy/radiation side effects was present in 38/45 patients with PE. Classic symptoms of PE were only seen in 10/45 patients. Of 57 patients with DVT/PE with positive D-Dimer 10 asymptomatic patients were on Avastin at the time of diagnosis. The median D Dimer value for 44 positive patients was 2.43 (0.57-23.95).Of the 57 positive patients 52 (91.2%) were treated with full anticoagulation- lovenox (n-35), coumadin (n-8), eliquis (n-7) and xeralto (n-2). The IVC filter was placed in 6 patients.High risk patients were fully anticoagulated for 1-3 months. Patients with resolution of PE/DVT were switched to preventive dose of anticoagulants. Two patients had h/o hypercoagulable disorder. Two patients had symptomatic ICH on lovenox and 1 had asymptomatic sub centimeter ICH on Xeralto. Conclusion- D Dimer is very helpful in the early detection of DVT/PE in high grade glioma patients. Patients with excessive Fatigue and somnolence can be screened for PE using D-Dimer.The D Dimer screening can help with early detection of DVT/PE in patients being treated with Avastin.
SURG-08. AWAKE CRANIOTOMY WITH BRAIN MAPPING FOR DIFFUSE LOW-GRADE GLIOMA: CASE REPORT OF INSTITUTIONAL EXPERIENCE IN OVERCOMING HURDLES IN A LOW-RESOURCE SETTING
Authors: Kirby Manigos, Kevin Paul Ferraris, Joseph Erroll Navarro, Kenny Seng, Jose Carlos Alcazaren
Journal: Neuro-Oncology (2020)

Abstract Maximal safe resection of low-grade gliomas located in functional areas of the cortex while avoiding postsurgical neurologic deficits can be achieved by awake craniotomy with brain mapping. The effectiveness of this surgical technique is fairly established in the developed world, however it remains to be routinely applied in low-middle income countries due to limited resources and lack of equipment. We present the case of a 44 year-old, right-handed male who had a 2-year history of focal aware motor seizures but was otherwise neurologically intact. Neuropsychological testing revealed no cognitive impairment. Cranial magnetic resonance imaging (MRI) revealed a non-enhancing, ill-defined tumor centered on the left insula and extending into the frontotemporal opercula, corona radiata, and posterior limb of the internal capsule—hypointense by T1-weighted sequence and hyperintense by T2-weighted sequence, thus radiographically consistent with diffuse low-grade glioma. Blood-oxygen-level-dependent functional MRI revealed left hemispheric language dominance in the cortex overlying the tumor, but with no motor cortex involvement. The patient underwent a protocol-driven awake craniotomy, intraoperative positive brain mapping using standard cortical stimulator, transsylvian and transcortical transopercular microsurgical approaches to achieve greater than 80% excision of the tumor. Postoperatively, the patient was seizure-free and with similar neurocognitive status prior to the surgery. The patient had been following up for standard adjuvant chemotherapy and radiotherapy. Avoidance of postsurgical neurologic deficits and maximal cytoreduction can still be achieved by awake craniotomy with brain mapping in settings with limited resources. Despite the lack of other perioperative tools and adjuncts such as diffusion tensor imaging, intraoperative ultrasonography, and even intraoperative MRI that are routinely available in high-resource settings, we illustrate in this case that comparable outcomes could be achieved by overcoming hurdles and aiming for the asymptote to the up-to-date and ideal neurosurgical treatment for diffuse low-grade gliomas.
MBRS-03. SINGLE NUCLEUS TRANSCRIPTOME PROFILES FROM HUMAN DEVELOPING CEREBELLUM REVEAL POTENTIAL CELLULAR ORIGINS OF MEDULLOBLASTOMA BRAIN TUMORS
Authors: Konstantin Okonechnikov, Mari Sepp, Kevin Leiss, Lena Kutscher, Kati Ernst, David Jones, Natalie Jäger, Kristian W Pajtler, Henrik Kaessmann, Stefan M Pfister
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma (MB) is a highly malignant pediatric brain tumor originating from the cerebellum and brainstem. Identification of molecular subgroups forming this heterogeneous tumor entity was initially achieved from transcriptome characterization and further strengthened using DNA methylation profiling. While subgroup classification improved clinical diagnosis and treatment options, the lack of knowledge of the cell-of-origin for some of the subgroups hinders further treatment improvements. In addition identification of the precise cells of origin for each subgroup could help to understand tumor cell biology. Single cell sequencing is the optimal way to solve this task; recently, there were attempts to uncover putative MB cell-of-origin by using such information obtained from mouse embryonic cerebellum. However, such a comparative strategy can miss important results due to the differences between mouse and human. To solve this issue, we performed global single nucleus sequencing on human cerebellum pre- and postnatal materials across several developmental time points and generated transcriptome profiles from ~200k single cells. We identified known cell types forming the human cerebellum and performed detailed comparison of normal cells to RNA-seq bulk data from MB brain tumors across all subgroups. By selecting an optimal analysis strategy, we verified granule neuron precursors as cells of origin for the SHH MB subgroup. Additionally, we also found other cell types in conjunction with the remaining MB subgroups, suggesting new potential targets for investigation. Notably, this strategy can be further applied to the examination of other brain tumors and has perspectives in medical application.
BIOM-35. MULTI ANALYTE ASSAY FOR NON-INVASIVE DIAGNOSIS OF BRAIN TUMORS
Authors: Dadasaheb Akolkar, Darshana Patil, Pooja Fulmali, Sneha Puranik, Sachin Apurwa, Revati Patil, Pradip Fulmali, Archana Adhav, Priti Mene, Pratik Paranjape, Snehal Golar, Swapnil Puranik, Shoeb Patel, Vishal Ranjan, Rohit Chougule, Shabista Khan, Raja Dhasarathan, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar
Journal: Neuro-Oncology (2020)

Abstract The diagnosis of Central Nervous System (CNS) malignancies such as Gliomas in individuals presenting with Intracranial Space Occupying Lesions (ICSOL) is based on histopathological examination (HPE) of tumor tissue obtained by an invasive brain biopsy. However, brain biopsies are resource intensive and are associated with procedural risks such as haemorrhage, morbidity and mortality. The present study evaluated a non-invasive approach for diagnosis of CNS-M in symptomatic individuals based on evaluation of circulating tumor analytes in peripheral blood. The non-invasive multi-platform approach for diagnosis of CNS-M included Immunocytochemistry (ICC) profiling and Fluorescence in situ Hybridization (FISH) of Circulating Tumor Cells (CTCs) and Digital Droplet PCR (ddPCR) of cell-free tumor DNA (ctDNA) and exosomal mRNA. Performance characteristics of each platform were evaluated using blood and tissue samples from 445 individuals including 227 known cases of CNS-M, 47 known cases of benign CNS conditions (CNS-B), 141 known cases of other cancers with brain metastases (OTH-M) and 30 asymptomatic individuals (ASYM). In a set of 37 samples from individuals with radiological ICSOL, suspected of malignancy (CNS-S) complete diagnostic work-up was performed with ICC, FISH and ddPCR. Glial CTCs were detected in 88.8% of 227 CNS-M and undetectable in 89.4% of 47 CNS-B or 100% of 141 OTH-M, indicating high sensitivity and specificity, respectively. The multi-analyte approach discerned CNS-M from CNS-B as well as OTH-M with 91.7% accuracy and accurately inferred lineage in 84.6% of cases. This non-invasive multi-analyte approach can diagnose CNS-M with an accuracy not inferior to standard HPE, can substitute invasive biopsies in most cases and is particularly helpful in cases where a biopsy is not viable.
Coding Errors in Study of Factors Associated With SARS-CoV-2 Antibodies in Health Care Personnel
Authors: Karina W. Davidson
Journal: JAMA (2020)

To the Editor On behalf of my coauthors, I write to report errors in our Research Letter, "Prevalence of SARS-CoV-2 Antibodies in Health Care Personnel in the New York City Area," published online first on August 6, 2020, and in the September 1, 2020, issue of JAMA.1
Improving the Outcome of Childhood Pulmonary Arterial Hypertension: The Effect of Bosentan in the Setting of a Dedicated Pulmonary Hypertension Clinic⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Ian Adatia
Journal: Journal of the American College of Cardiology (2005)
Spontaneous Regression of Miliary Pattern after Delivery. Benign Pulmonary Metastasizing Leiomyoma
Authors: Pierre Le Guen, Nicolas Poté, Lise Morer, Camille Taillé
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Spontaneous Regression of Miliary Pattern after Delivery. Benign Pulmonary Metastasizing Leiomyoma." American Journal of Respiratory and Critical Care Medicine, 203(7), pp. 906–907
Mild X-linked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife
Authors: Aleksandra M. Żurowska, Olga Bielska, Patrycja Daca-Roszak, Maciej Jankowski, Maria Szczepańska, Dagmara Roszkowska-Bjanid, Elżbieta Kuźma-Mroczkowska, Małgorzata Pańczyk-Tomaszewska, Anna Moczulska, Dorota Drożdż, Despina Hadjipanagi, Constantinos Deltas, Danuta Ostalska-Nowicka, Alina Rabiega, Janina Taraszkiewicz, Katarzyna Taranta-Janusz, Anna Wieczorkiewicz-Plaza, Katarzyna Jobs, Judyta Mews, Kinga Musiał, Anna Jakubowska, Hanna Nosek, Anna E. Jander, Constantina Koutsofti, Anna Stanisławska-Sachadyn, Dominka Kuleszo, Ewa Ziętkiewicz, Beata S. Lipska-Ziętkiewicz
Journal: Kidney International (2020)

A study of 269 children enrolled into a National Registry for children with persistent glomerular hematuria identified 131 individuals with genetically confirmed X-linked Alport Syndrome. A single variant c.1871G>A p.Gly624Asp (G624D) in COL4A5 was predominant and accounted for 39% of X-linked Alport Syndrome in unrelated Polish families (44 of 113). To evaluate its origins, the genetic variation in a 2.79 Mb segment encompassing the COL4A5 locus on chromosome X was assessed. All G624D alleles were found on the same rare haplotype background, indicating a founder effect dating back to the 12-13th century. The phenotypic data of 131 children with X-linked Alport Syndrome and their 195 affected adult relatives revealed that the G624D variant was associated with a significantly milder clinical course in comparison to other pathogenic COL4A5 variants. Furthermore the clinical course of this genetically uniform cohort was milder than that observed in individuals with other COL4A5 missense mutations. In spite of the benign clinical manifestation throughout childhood and early adulthood, the G624D variant confers significant risk for both kidney failure and deafness in males, albeit 20-30 years later than that observed in individuals with other COL4A5 pathogenic variants (50% cumulative risk of starting dialysis at 54 years (95% confidence interval: 50-62) v. 26 years (95% confidence interval: 22-30)). Thus, males with G624D are candidates for existing and emerging therapies for Alport Syndrome.
TMOD-17. ONCOLYTIC POLIOVIRUS AS A PROBE FOR MECHANISMS OF IMMUNE RESISTANCE IN GLIOBLASTOMA
Authors: Yuanfan Yang, Michael Brown, Matthias Gromeier, Darell Bigner
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma is an immunologically cold tumor that employs multiple resistance mechanisms to escape activation of both innate and adaptive immunity. Transient immune activation and responses induced by immunotherapies in glioblastoma are almost always suppressed by potent intrinsic and extrinsic resistance mechanisms, limiting therapeutic efficacy. PVSRIPO is a recombinant poliovirus/rhinovirus chimera that elicits robust innate immune activation through infecting and lysing glioblastoma cells expressing the human poliovirus receptor (CD155), and through sublethal infection of tumor associated macrophages, setting the stage for lingering viral replication. We have constructed a pathological model using murine CT2ACD155 intracranial tumors stereotactically infused with a single dose of PVSRIPO (5×107 pfu) or mock control to study the response of glioblastoma in an immune competent in vivo tumor microenvironment. Tumor bearing brains were harvested before therapy and on days 2, 4, 6, 9, 12 post therapy for histology. On day 4 post therapy, histopathology showed &amp;gt; 90% shrinkage of intracranial tumor diameter (n= 6/6). Residual tumor is surrounded by a necrotic rim on histology with profound infiltration of F4/80+ macrophages and substantially reduced expression of Ki-67 on IHC compared to controls. Other markers including CD3, CD8 and Cleaved-Caspase 3 showed no difference in tumors of both groups. Interestingly, most residual tumor progressed on day 6 post therapy and caught up with the size of control tumor by day 9. Long-term remission of tumor occurred in only 10% of mice. This model is valuable in studying the mechanisms of intrinsic resistance and the timeline of resistance to develop in order to obtain more durable immunotherapy responses in glioblastoma. Future steps are to track inflammation induced by viral infection by RNAseq, and to find potential therapeutic interventions (including blocking PD1:PD-L1 axis) to mitigate therapy resistance in this preclinical model.
Structural Racism in the COVID-19 Pandemic: Moving Forward
Authors: Maya Sabatello, Mary Jackson Scroggins, Greta Goto, Alicia Santiago, Alma McCormick, Kimberly Jacoby Morris, Christina R. Daulton, Carla L. Easter, Gwen Darien
Journal: The American Journal of Bioethics (2020)

The COVID-19 pandemic has taken a substantial human, social and economic toll globally, but its impact on Black/African Americans, Latinx, and American Indian/Alaska Native communities in the U.S. is unconscionable. As the U.S. continues to combat the current COVID-19 cycle and prepares for future pandemics, it will be critical to learn from and rectify past and contemporary wrongs. Drawing on experiences in genomic research and intersecting areas in medical ethics, health disparities, and human rights, this article considers three key COVID-19-related issues: research to identify remedies; testing, contact tracing and surveillance; and lingering health needs and disability. It provides a pathway for the future: community engagement to develop culturally-sensitive responses to the myriad genomic/bioethical dilemmas that arise, and the establishment of a Truth and Reconciliation Commission to transition the country from its contemporary state of segregation in healthcare and health outcomes into an equitable and prosperous society for all.