tbuckley/cabot-search huggingface dataset:
Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France
Authors: Rebecca Grant, Tiffany Charmet, Laura Schaeffer, Simon Galmiche, Yoann Madec, Cassandre Von Platen, Olivia Chény, Faïza Omar, Christophe David, Alexandra Rogoff, Juliette Paireau, Simon Cauchemez, Fabrice Carrat, Alexandra Septfons, Daniel Levy-Bruhl, Alexandra Mailles, Arnaud Fontanet
Journal: The Lancet Regional Health - Europe (2021)

We aimed to assess the settings and activities associated with SARS-CoV-2 infection in the context of B.1.617.2 (Delta) variant circulation in France, as well as the protection against symptomatic Delta infection.In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 23 May and 13 August 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire and multivariable logistic regression analysis was used to determine the association between acute SARS-CoV-2 infection and recent activity-related exposures, past history of SARS-CoV-2 infection, and COVID-19 vaccination.We did not find any differences in the settings and activities associated with Delta versus non-Delta infections and grouped them for subsequent analyses. In multivariable analysis involving 12634 cases (8644 Delta and 3990 non-Delta) and 5560 controls, we found individuals under 40 years and attending bars (aOR:1.9; 95%CI:1.6-2.2) or parties (aOR:3.4; 95%CI:2.8-4.2) to be at increased risk of infection. In those aged 40 years and older, having children attend daycare (aOR:1.9; 95%CI:1.1-3.3), kindergarten (aOR:1.6; 95%CI:1.2-2.1), primary school (aOR:1.4; 95%CI:1.2-1.6) or middle school (aOR:1.3; 95%CI:1.2-1.6) were associated with increased risk of infection. We found strong protection against symptomatic Delta infection for those with prior infection whether it was recent (2-6 months) (95%; 95%CI:90-97) or associated with one dose (85%; 95%CI:78-90) or two doses of mRNA vaccine (96%; 95%CI:87-99). For those without past infection, protection was lower with two doses of mRNA vaccine (67%; 95%CI:63-71).In line with other observational studies, we find reduced vaccine effectiveness against symptomatic Delta infections. The settings and activities at increased risk of infection indicate where efforts to reinforce individual and public health measures need to be concentrated.
Abstract 12319: 16alpha-Hydroxyestrone Downregulates SOX17 During the Development of Pulmonary Arterial Hypertension
Authors: Shreya Sangam, Tae-Hwi Schwantes-An, John Zagorski, Yinan Shi, Seth Morrisroe, Todd Cook, Amanda Fisher, Andrea Frump, Anna Coleman, Haiyang Tang, Howard Crawford, Katie Lutz, Michael W Pauciulo, Ketul R Chaudhary, Duncan J Stewart, Tim Lahm, William C Nichols, Ankit A Desai
Journal: Circulation (2021)

Introduction: Sexual dimorphism in pulmonary arterial hypertension (PAH) is attributed, in part, to estrogen signaling. 16α-hydroxyestrone (16αOHE) is considered a major contributor to PAH pathogenesis. Recent genetic studies have also suggested that deficiency of SOX17, an endothelial cell (EC)-specific transcription factor, contributes to PAH risk. While functional studies of SOX17 are absent, we hypothesized that 16αOHE contributes to PAH, in part, via, SOX17 downregulation. Methods/Results: Sox17 expression was reduced in 3 animal PAH models and in human pulmonary artery ECs (HPAECs) isolated from patients with PAH (vs controls). Inducible Tie2-specific Sox17 knockout ( Sox17 EC-/- ) mice exhibited increased right ventricular systolic pressure (RVSP), RV hypertrophy (RVH), and PA wall thickness (PAWT) after chronic hypoxia (CH) (Fig 1A). Inducible Tie2- Sox17 transgenic overexpressing ( Sox17 Tg ) mice attenuated CH-induced PH (Fig 1B). While not evident across murine sex, Sox17 expression was increased in baseline lungs from male compared to female rats. Supporting in silico evidence of estrogen response elements (ERE) on the SOX17 promoter, HPAECs exposed to 16αOHE reduced SOX17 expression and promoter luciferase activity via ERα, which was partly negated by serial ERE mutagenesis (Fig 1C ) . Lungs from ERα loss-of-function mutant rats (vs control) confirmed in vivo reductions of Sox17 expression. Sox17 Tg mice attenuated 16αOHE-mediated PH after CH (Fig 1D). To translate these data, we identified a functional coding SNP in the ESR1 gene (encoding ERα), rs746432, previously shown to reduce transcriptional activity of ERα. The SNP was associated with reduced pulmonary vascular resistance in patients with PAH (n=702, Fig 1E) in adjusted analyses. Conclusion: Validating genetic studies, SOX17 deficiency augments preclinical PAH. 16αOHE mediates PH development via downregulation of SOX17, linking SOX17 genetics with the observed sexual dimorphism.
NCOG-32. PROGNOSTIC IMPLICATIONS OF SIZE OF PITUITARY MACROADENOMAS: A COMPARATIVE ANALYSIS OF GIANT ADENOMAS WITH NON-GIANT MACROADENOMAS
Authors: Sanam Mir Ghazi, Muhammad Bilal Tariq, Fauzan Alam Hashmi, Asra Tanwir, Ahsan Ali Khan, Muhammad Shahzad Shamim, Meher Angez, Syed Ather Enam
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND In this study we compared giant pituitary adenomas (GPAs) and non-giant pituitary macroadenomas (nGPAs) on the basis of presenting complaints, surgical procedures, tumor resections and outcomes. METHODS A retrospective analysis (2006-2017) of pituitary macroadenomas was performed where tumors were divided into two groups; tumors greater than 4 cm were classified as GPAs while macroadenomas smaller than 4 cm were termed as nGPAs. Both GPA and nGPA had 75 patients in each group. RESULTS The most common complaint of all patients was visual deterioration (77.3% of patients with nGPAs and 89.3% of patients with GPAs). Visual field defects were present in 55 patients (73.3%) in the nGPA group compared to 68 patients (90.7%) in the GPA group (p=0.006). The mean volume of nGPAs was 6.3 cm3 (range 0.45 cm3 to 22 cm3 while the mean volume of GPAs was 30.1 cm3 (range 10.8 cm3 to149.4 cm3) (p=0.001). The mean extent of resection was 88.9% for nGPAs whereas the mean extent of resection was 76.7% for GPAs (p=0.03). Craniotomy was required only in the GPA group (5 patients, 6.7%) (p=0.023). Tumor recurrence/progression was seen in 9.3% of patients with nGPAs and 44% of patients with GPAs (p=&amp;lt; 0.001). Re-do surgery was required in 2.7% of nGPA cases (via transsphenoidal approach) and 32% of GPA cases; in this GPA subgroup, 22.7% patients required transsphenoidal surgeries while 9.3% patients required transcranial surgeries. Stereotactic radiosurgery in recurrence/progression accounted for 4% of nGPA patients and 22.7% of GPA patients. There were 3 mortalities, all in GPA group. Overall, nGPA group had better postoperative course as compared to GPA group. CONCLUSION The frequency of preoperative symptoms in GPAs is more significant and associated with lesser chances of gross total tumor resection, higher rates of recurrence, and worse postoperative course in comparison to nGPAs.
BIOM-11. THE PROGNOSTIC VALUE OF ROUTINE AND SPECIALIZED BLOOD TESTING IN GLIOBLASTOMA: A SYSTEMATIC REVIEW
Authors: Arthur van der Boog, Fia Cialdella, Danique Bruil, Karlijn Smitt, Filip de Vos, Joost Verhoeff
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND A combination of clinical characteristics, radiological findings and tissue markers is used in the assessment of glioblastoma prognosis and prediction of treatment response. The value of routine blood tests as a tool of prognosis has been a subject of debate. In addition to increased complication rate in subsequent resections and radiological uncertainty in treatment monitoring, there is a need to monitor tumor markers in a minimally invasive manner, as molecular characterization becomes more important in the management of glioblastoma. The objective of this review is to evaluate the prognostic value of any blood marker during the course of disease and treatment in glioblastoma. METHODS We researched Pubmed and Embase for clinical studies including cohort studies and randomized controlled trials that included at least 10 adult patients and blood testing during course of disease. We extracted data on clinically relevant endpoints, i.e. overall survival (OS) or progression-free survival (PFS), in accordance with the PRISMA statements. RESULTS The search strategy yielded 6389 unique articles, of which 150 met the inclusion criteria. 37 studies found an association between survival outcomes and pre-operative markers including complete blood count (erythrocytes and leukocytes with differentiation characteristics), inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), coagulability markers (prothrombin time, activated partial thromboplastin time and D-dimer), albumin, lactate dehydrogenase and glucose. Furthermore, 10 studies reported a correlation between changes in platelets, erythrocytes and leukocytes during course of disease and treatment and OS. Finally, serum and plasma levels of markers including various proteins, microRNAs and microvesicles were associated with PFS and OS. CONCLUSION The results of this study suggest that routine and specialized blood tests provide additive information on OS and PFS in glioblastoma. These promising findings highlight the need for further investigation of blood testing for biomarker evaluation.
Heterogeneity of Minimal/Measurable Residual Disease (MRD) Practices in Adult B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) in the United States
Authors: Juliana E. Hidalgo-Lopez, Gail J. Roboz, Brent Wood, Michael Borowitz, Elias J. Jabbour, Kelly Velasco, Ehab Elkhouly, Babatunde Adedokun, Faraz Zaman, Karim Iskander, Aaron C. Logan
Journal: Blood (2021)
Superiority of Leukemic Stem Cell-Based Minimal Residual Disease Assay to Traditional Multiparameter Flow Cytometry-Based Method for Relapse Prediction in AML Patients: A Prospective Study with Randomized Training and Validation Sets
Authors: Siqi Li, Lan-Ping Xu, Yu Wang, Xiaohui Zhang, Huan Chen, Yu-Hong Chen, Fengrong Wang, Wei Han, Yuqian Sun, Chenhua Yan, Meng Lyu, Feifei Tang, Xiao-Dong Mo, Kai-Yan Liu, Yingjun Chang, Xiao Jun Huang
Journal: Blood (2021)
EXTH-56. ZIKA VIRUS TREATMENT SIGNIFICANTLY PROLONGS SURVIVAL IN A GLIOBLASTOMA PATIENT DERIVED XENOGRAFT MODEL
Authors: Parvez Akhtar, Samuel Zwernik, Deborah Donohoe, Catherine Warner, Dmitry Bosenko, Richard Rovin
Journal: Neuro-Oncology (2021)

Abstract The poor median survival for patients with glioblastoma (GBM) of 15 months has not budged for the past 15 years, when the current standard treatment was first approved. There is no standard of care chemotherapy for recurrent GBM. We previously showed that Zika virus (ZIKV) tropism for GBM cells is mediated through the receptor tyrosine kinase, AXL. This infection is cytotoxic. In this study we show that ZIKV is an effective oncolytic virus in a patient derived xenograft model. Fox N1 Nude homozygous female mice 6-8-weeks-old were grouped into 4 experimental arms: two patient derived cell lines, each with a ZIKV treated and a control group. There were 12 mice in each arm. Animals received subcutaneous flank injections of GBM 8049 or its AXL CRISPR knockout 8049 AXLKO (2x106 cells). When tumors reached 200 mm3, mice received intra-tumoral injection of 2.5x106 ZIKV particles or saline. ZIKV induced complete tumor remission in 22 of 24 animals (8049: 11/12; 8049 AXLKO: 11/12). There was no tumor remission in the saline treated animals. Median survival of 8049 and 8049 AXLKO ZIKV treated mice was 124 days and 125 days, respectively. This is compared to median survival of control animals 8049: 42 days; 8049 AXLKO: 46 days (P= 0.001). Among ZIKV treated mice, there were two recurrences: one in the 8049 tumor (24 days after significant tumor remission) and one 8049 AXLKO tumor (7 days after significant tumor remission). We conclude that ZIKV should be considered a candidate oncolytic virus for GBM.
Abstract 14330: Contraction-Relaxation Coupling is Unaltered by Heart Failure Status in Human Myocardium
Authors: Farbod Fazlollahi, Amanda Huang, Nick Yavornitzky, Anna Wang, Kyra Peczkowski, Nancy Saad, Mohammed Mashali, Austin Hare, Courtney M Campbell, Bryan Whitson, Nahush Mokadam, Paul M Janssen
Journal: Circulation (2021)

The two main phases of the mammalian cardiac cycle are contraction and relaxation; however, whether these phases are linked in human myocardium is not well understood. Prior investigations have shown that the structural and biochemical myocardial remodeling secondary to exercise training and/or myocardial infarction does not disrupt contraction-relaxation (CR) coupling in the canine model system. In addition, in a wide variety of murine transgenic models targeting EC coupling, the coupling between contraction and relaxation was unaltered. Given the vast differences between inbred animal models and the human population, we investigated whether contraction and relaxation are also coupled in human myocardium, and if so, whether that coupling is affected by heart failure disease status. We retrospectively analyzed data from contractility measurements taken under conditions closely mimicking those in vivo and calculated the correlation between the maximal speed of contraction and the maximal speed of relaxation in human ventricular multicellular preparations. We categorized our data based on heart failure status as follows: non-heart failure, heart failure with ischemic cardiomyopathy, or heart failure with non-ischemic cardiomyopathy. In every case isolated right ventricular trabeculae and/or left ventricular trabeculae (n=53 subjects LV and RV analyzed, 38 subjects only LV, 27 subjects only RV) were isolated from freshly explanted human hearts. Multicellular preparations were then electrically paced at different muscle lengths, frequencies, and with increasing β-adrenoceptor stimulation. In all conditions, contraction and relaxation were very tightly linearly correlated regardless of disease category (typical R 2 of &gt;0.98). While the mechanism governing this coupling is unknown, based on data form this study and past studies, we posit that CR-coupling is a fundamental myocardial property that resides in the structural arrangement of proteins at the level of the sarcomere at the basis of cross-bridge cycling.
Increasing Access to Preventive Services Is Needed—No Medicare Beneficiary Left Behind
Authors: Joshua D. Niforatos, Alexander R. Zheutlin, Jeremey B. Sussman
Journal: JAMA Network Open (2021)

Ganguli and colleagues 1 explore national trends in receipt of preventive services among older adults with multiple comorbidities enrolled in Medicare based upon having a usual care clinician (UCP).
European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer
Authors: I. Vergote, A. González-Martín, I. Ray-Coquard, P. Harter, N. Colombo, P. Pujol, D. Lorusso, M.R. Mirza, B. Brasiuniene, R. Madry, J.D. Brenton, M.G.E.M. Ausems, R. Büttner, D. Lambrechts, I. Vergote, M. Ausems, B. Brasiuniene, J. Brenton, R. Büttner, N. Colombo, A. González-Martín, P. Harter, D. Lambrechts, D. Lorusso, R. Madry, M.R. Mirza, P. Pujol, I. Ray-Coquard, M. Abreu, S. Balboni, S. Banerjee, M. Barberis, M.P. Barretina Ginesta, J.-F. Baurain, M. Bignami, L. Bjorge, P. Blecharz, I. Bruchim, M. Capilna, N. Cerana, A. Cicchetti, D. Collins, N. Concin, M. D’Incalci, B. Davidson, T. de la Motte Rouge, P. De Iaco, F. Demirkiran, H. Denys, T. Doerk, A. Dorum, A. Ferrero, A.P. Fidalgo, M. Genuardi, L. Gladieff, R. Glasspool, C. Grimm, M. Gultekin, E. Hahnen, A. Hasenburg, A. Hegmane, V. Heinzelmann, E. Hogdall, R. Janavicius, S. Jarmalaite, R. Kalachand, R. Kaneva, S. Kilickap, R. Kocian, D. Kolencik, R. Kristeleit, A. Kryzhanivska, A. Leary, B. Lemley, M. Ligtenberg, J.A. López-Guerrero, C.J. Lord, E. Avall-Lundqvist, J. Maenpaa, S. Mahner, F. Marmé, C. Marth, I. McNeish, S. Merkelbach-Bruse, M. Mourits, N. Normanno, A. Oaknin, K. Ojamaa, C. Papdimitriou, F. Penault-Llorca, A.M. Perrone, S. Pignata, E. Pikarsky, E. Rouleau, M. Rubio, A. Sapino, B. Schmalfeldt, J. Sehouli, R. Shapira, K.D. Steffensen, V. Sukhin, J. Syrios, Z. Szallasi, C. Taskiran, M. Terzic, M. Tischkowitz, I. Toth, K. Van de Vijver, M.A. Vardar, B. Wasag, P. Wimberger, E. Witteveen
Journal: Annals of Oncology (2021)

Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition.
Abstract 13952: A Novel Genetic Mini-Pig Model of Cardiac Myosin-Binding Protein C (MYBPC3) Dysfunction: Evidence for Altered Sarcomere Structure and Systolic/Diastolic Functional Reserve in vivo
Authors: Carlos L del Rio, Weikang Ma, David Ryba, Henry Gong, Marcus Henze, Sampath K Gollapudi, Robert Anderson, Suman Nag, Christopher Rogers, Thomas Irving
Journal: Circulation (2021)

Introduction: Mutations in MYPBC3, the gene encoding cardiac Myosin-Binding Protein C (cMyBP-C), a regulatory sarcomeric protein, are known to play a pathogenic role in hypertrophic cardiomyopathy ...
RADT-28. RECURRENT MENINGIOMA WITH 1p/22q SOMATIC MUTATION OF GNAS: A CASE REPORT
Authors: Weiping Hong, Lei Wen, Changguo Shan, Minting Ye, yanying Yang, hui Wang, Linbo Cai
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE Refractory meningioma faces the problems of low total resection rate, high recurrence rate and high disability rate. Here we report a patient with recurrent refractory meningioma who was benefited from precision treatment plan based on molecular diagnosis. METHODS Molecular diagnosis by next generation sequencing (NGS) test was used to test the hybridized captured DNA in the tumor tissue of the patient. RESULTS The 53-year-old female diagnosed with meningioma was admitted to our hospital after tumor progression was observed for 3 weeks. She had received 4 operations for the tumor previously. The first three times of postoperative pathology indicated WHO Ⅰ grade meningioma. The fourth postoperative pathology showed excessive meningioma, with active growth of tumor cells in some areas and small focal necrosis, WHO Ⅰ- fair grade. Somatic mutation GNAS p.F309VFS *25 and deletion of the short arm of chromosome 1 / long arm of chromosome 22 were also found (1P / 22Q) by NGS test. The second recurrent foci showed partial amplification of 17q and 19, except for 1p/22q deletions, compared with the first. Meningiomas with 1p/22q deletion are type C meningiomas (more than half are grade WHO Ⅰ). Meningiomas have been shown to be highly vascularized neoplasms, with a 2-fold increase in VEGF expression in atypical meningiomas and a 10-fold increase in malignant meningiomas. According to the molecular diagnosis results, the precise treatment plan was determined: concurrent chemoradiotherapy, followed by anti-VEGF-targeted drugs combined with temozolomide for 2 months. The residual lesions were significantly reduced after treatment. CONCLUSION This case is the first to report a meningioma with pituitary tumor driver gene GNAS mutation, which is more prone to recurrence due to the combination of 1P / 22Q chromosome mutation. Molecular diagnosis can guide precise treatment to benefit patients.
Morel–Lavallée Lesion
Authors: Young-Hoon Kim, Hyung-Youl Park
Journal: New England Journal of Medicine (2021)

A 36-year-old man presented with a large mass on his back after he slipped on the stairs and slid down on his back. Magnetic resonance imaging showed a large, encapsulated, subcutaneous, suprafascial lesion consistent with a Morel–Lavallée lesion.
Abstract 10027: Pulsatile Load, Rather Than Cardiac Power Output, for the Right Ventricle Determines the Prognosis in Heart Failure Patients
Authors: Yasuyuki Chiba, Hiroyuki Iwano, Ko Motoi, Suguru Ishizaka, Shingo Tsujinaga, Asuka Tanemura, Michito Murayama, Shinobu Yokoyama, Masahiro Nakabachi, hisao nishino, Kazunori Okada, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Journal: Circulation (2021)

Background: Although cardiac power output (CPO), a parameter of cardiac performance, for the left ventricle (LV) is reported to be a powerful prognostic indicator in heart failure (HF), significance of the right ventricular (RV) CPO in HF has not been elucidated. On the other hand, RV pulsatile load stands for one of the prognostic markers in HF. We thus investigated the relationship of the RV CPO and pulsatile load to the outcome in HF. Methods: Right heart catheterization and echocardiography were performed in 231 HF patients (62±16 years, LV ejection fraction 42±18%). Invasive and noninvasive CPOs were calculated from mean systemic or pulmonary arterial pressures and cardiac output for the LV and RV. LV CPO was then corrected by LV mass (LV CPO/M). Pulmonary artery compliance (PAC) and the ratio of acceleration time to ejection time (AcT/ET) of the RV outflow velocity were used as parameters of RV pulsatile load. Cardiac death, HF hospitalization, ventricular arrhythmia and LVAD implantation after the examination were recorded. Results: Noninvasive CPOs were moderately correlated with invasive ones (LV: R=0.73, RV: R=0.58, P &lt;0.001 for both). During a median follow-up period of 441 days, cardiac events occurred in 57 patients. Using the cut-off of median values, lower LV CPO/M was associated with higher event rates, however, RV CPO did not discriminate the risk of future cardiac events. In contrast, higher RV pulsatile load was associated with higher event rates regardless of the level of LV CPO/M ( Figure ). In multivariable Cox proportional hazard analyses, echocardiographic LV CPO/M and AcT/ET both determined cardiac events independently of age, NYHA classification, LV ejection fraction and plasma brain natriuretic peptide levels. Conclusion: Pulsatile load, rather than CPO, for the RV was associated with cardiac events in HF. Furthermore, combination of echocardiographic LV CPO/M and AcT/ET could become a novel noninvasive prognostic indicator in HF patients.