tbuckley/cabot-search huggingface dataset:
2021 Update on Diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management
Authors: Sandra Susanibar‐Adaniya, Stefan K. Barta
Journal: American Journal of Hematology (2021)

Diffuse large B cell lymphoma (DLBCL), the most common type of Non-Hodgkin lymphoma (NHL), comprises a heterogeneous group of diseases with different biology, clinical presentations, and response to treatment. R-CHOP remains the mainstay of therapy and can achieve long-term disease control in nearly 90% of patients presenting with limited-stage and in up to 60% of those presenting with advanced stages. Advances on the understanding of the genetic landscape and molecular features of DLBCL have identified high-risk subsets with poor outcomes to chemo-immunotherapy that are actively being studied in clinical trials. Novel therapies could potentially improve outcomes for patients with high-risk disease. Studies evaluating risk-adapted therapy based on classification by cell of origin (COO) and molecular features are ongoing. Developments in the fields of immunotherapy, mostly with adoptive T-cell therapy, have significantly improved the outcomes of patients with relapsed refractory disease. In this review, we will summarize the recent data and discuss ongoing efforts to improve DLBCL treatment in the frontline and relapsed refractory settings.
Integrating imaging and RNA-seq improves outcome prediction in cervical cancer
Authors: Jin Zhang, Ramachandran Rashmi, Matthew Inkman, Kay Jayachandran, Fiona Ruiz, Michael R. Waters, Perry W. Grigsby, Stephanie Markovina, Julie K. Schwarz
Journal: Journal of Clinical Investigation (2021)

Approaches using a single type of data have been applied to classify human tumors. Here we integrate imaging features and transcriptomic data using a prospectively collected tumor bank. We demonstrate that increased maximum standardized uptake value on pretreatment 18F-fluorodeoxyglucose-positron emission tomography correlates with epithelial-to-mesenchymal transition (EMT) gene expression. We derived and validated 3 major molecular groups, namely squamous epithelial, squamous mesenchymal, and adenocarcinoma, using prospectively collected institutional (n = 67) and publicly available (n = 304) data sets. Patients with tumors of the squamous mesenchymal subtype showed inferior survival outcomes compared with the other 2 molecular groups. High mesenchymal gene expression in cervical cancer cells positively correlated with the capacity to form spheroids and with resistance to radiation. CaSki organoids were radiation-resistant but sensitive to the glycolysis inhibitor, 2-DG. These experiments provide a strategy for response prediction by integrating large data sets, and highlight the potential for metabolic therapy to influence EMT phenotypes in cervical cancer.
Use of nivolumab (N) and cabozantinib (C) for treatment of the metastatic renal cell carcinoma (mRCC) in the Veneto region: Results of AMOUR study.
Authors: Marco Maruzzo, Alberto Bortolami, Dario Palleschi, Andrea Zivi, Maurizio Nicodemo, Donata Sartori, Rocco De Vivo, Fable Zustovich, Davide Bimbatti, Davide Pastorelli, Giuseppe Dione Vultaggio, Mariella Soraru', Melissa Ballestrin, Giulia Zanchetta, Caterina Modonesi, Paola Randisi, Carmen Barile, Gino Perri, Umberto Basso, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2021)

290 Background: Second (2L) or third-line (3L) treatment options for mRCC have dramatically changed in the last years. The standard of care as per Italian Regulatory Agencies approvals is N or C. To date, there are no criteria for the choice between N and C, which both demonstrated OS gain in the pivotal trials. Methods: We planned a retrospective, real world analysis of the use of N and C as 2L and 3L treatment in 17 Oncology Units of Veneto Region. All consecutive patients (pts) with mRCC treated in advanced setting in 2017-2018 were included. Results: We identified 170 pts, 73% males, median age 68.4 years. All pts started a 2L treatment while only 59% received a 3L treatment. In our cohort, patients with NLR &gt; 3 at treatment start had a shorter OS (43 vs 90 months (mos), p &lt; 0.0001); IMDC classification maintained its prognostic role. In 2L, N was administrated in 108 pts (63%), C in 29 pts (17%); in 3L N was administrated in 42 pts (25%), C in 49 pts (29%). Reported oncologists’ reasons for 2L choice were: change of mechanism of action compared to first line (28%), response to previous TKI (21.2%), intolerance to TKI (17.6%), previous toxicity (12.9%), tumor burden (11.2%), age of the patient (4.1%). Median OS and PFS in 2L were 28.4 and 6.6 mos for N, 16.8 and 6.6 mos for 2L C. Median OS and PFS in 3L were 27 and 5.2 mos for N, 16.6 and 7.5 mos for C. 46 pts received the sequence of drugs N &gt; C, 12 the opposite sequence C &gt; N. Median OS for N &gt; C vs C &gt; N were 96.6 vs 36 mos (p &gt; 0.0001); median PFS for both the sequences were similar at 5.7 mos (p = ns). The cost per patient of the sequence N &gt; C is 51.606 € while for the sequence C &gt; N is 31.480,00 €. Between the two sequences a cost effectiveness per month of survival analysis was performed: the cost per month of OS for the sequence N &gt; C was 534,18 € while for the sequence C &gt; N was 874,46 €, heavily higher. Conclusions: In our real-world setting cohort, most of the pts received N as 2L treatment and a minority received C. Outcome of single drug are superimposable to published literature. With the limits of the retrospective nature of the study, with a cost per month of OS lower a much longer OS, the sequence N &gt; C appear to be a better treatment strategy.
Bone morphogenetic protein-2 as a novel biomarker for refractory chronic rhinosinusitis with nasal polyps
Authors: Jin Youp Kim, Suha Lim, Hee-Suk Lim, Yi-Sook Kim, Kyoung Mi Eun, Roza Khalmuratova, Yuju Seo, Joon Kon Kim, Young Seok Kim, Min-Kyung Kim, Siyeon Jin, Seung Cheol Han, Suyeon Pyo, Seung-No Hong, Jong-Wan Park, Hyun-Woo Shin, Dae Woo Kim
Journal: Journal of Allergy and Clinical Immunology (2021)
Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies
Authors: Elizabeth A. Jacobsen, David J. Jackson, Enrico Heffler, Sameer K. Mathur, Albert J. Bredenoord, Ian D. Pavord, Praveen Akuthota, Florence Roufosse, Marc E. Rothenberg
Journal: Annual Review of Immunology (2021)

The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Researchers using eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit.
Abstract 11634: Crosstalk Between Human IPSC-derived Lung Progenitors and Endothelial Cells Model Development of a De Novo Air-blood Barrier
Authors: Miriel Ho, Mirabelle S Ho, Duncan J Stewart
Journal: Circulation (2019)

Bioartificial lungs created using autologous induced pluripotent stem cell (iPSC) products may circumvent graft rejection to treat severe respiratory diseases. In vitro maturation of iPSC-derived l...
Correction to: The lncRNA LAMP5-AS1 drives leukemia cell stemness by directly modulating DOT1L methyltransferase activity in MLL leukemia
Authors: Wen-Tao Wang, Tian-Qi Chen, Zhan-Cheng Zeng, Qi Pan, Wei Huang, Cai Han, Ke Fang, Lin-Yu Sun, Qian-Qian Yang, Dan Wang, Xue-Qun Luo, Yu-Meng Sun, Yue-Qin Chen
Journal: Journal of Hematology & Oncology (2021)

The original article [1] contains an error in Fig. 6b for the image of western blot panels.
Endometrial Cancer Risk in Women With Germline <i>BRCA1</i> or <i>BRCA2</i> Mutations: Multicenter Cohort Study
Authors: Marthe M de Jonge, Cornelis D de Kroon, Denise J Jenner, Jan Oosting, Joanne A de Hullu, Marian J E Mourits, Encarna B Gómez Garcia, Margreet G E M Ausems, J Margriet Collée, Klaartje van Engelen, Irma van de Beek, Vincent T H B M Smit, Matti A Rookus, Geertruida H de Bock, Flora E van Leeuwen, Tjalling Bosse, Olaf M Dekkers, Christi J van Asperen
Journal: JNCI Journal of the National Cancer Institute (2021)

Endometrial cancer (EC) risk in BReast CAncer gene 1/2 (BRCA1/2) mutation carriers is uncertain; therefore, we assessed this in a large Dutch nationwide cohort study.
Treat physical and sexual violence against women as public health problem, says WHO
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The World Health Organization has said that physical and sexual violence against women should be treated as a public health problem and called for healthcare workers to be trained in “responding to the needs of survivors holistically and empathetically.”

It made the recommendation on the back of figures showing that nearly one in three women worldwide (30%) experienced physical or …
High <i>VHL</i> Expression Reverses Warburg Phenotype and Enhances Immunogenicity in Kidney Tumor Cells
Authors: Songbiao Zhu, Wenxi Ding, Yuling Chen, Weixuan Wang, Renhua Xu, Chongdong Liu, Xiaohui Liu, Haiteng Deng
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Clear cell renal cell carcinoma (ccRCC) is a frequently occurring renal cancer. The Von Hippel-Lindau disease tumor suppressor VHL, a known tumor suppressor gene, is frequently mutated in about 50% of patients with ccRCC. However, it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL. In the present study, we found that higher expression of VHL was correlated with the better disease-free survival (DFS) in ccRCC patients using The Cancer Genome Atlas (TCGA) datasets. We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition (EMT), sterol regulatory element-binding protein 1 (SREBP1)-regulated triglyceride synthesis, and cell proliferation. Proteomic analysis provided us a global view that VHL regulated four biological processes, including metabolism, immune regulation, apoptosis, and cell movement. Importantly, we found that VHL overexpression led to up-regulated expression of proteins associated with antigen processing and interferon-responsive proteins, thus rendering ccRCC cells more sensitive to interferon treatment. We defined an interferon-responsive signature (IRS) composed of ten interferon-responsive proteins, whose mRNA expression levels were positively correlated with DFS in ccRCC patients. Taken together, our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy.
Abstract 13130: Primary Prevention of Acute Rheumatic Fever and Rheumatic Heart Disease with Penicillin in South African Children with Pharyngitis: A Cost-Effectiveness Analysis
Authors: James Irlam, Bongani Mayosi, Mark Engel, Thomas Gaziano
Journal: Circulation (2012)

Introduction: Acute rheumatic fever (ARF) and subsequent rheumatic heart disease (RHD) remain a challenge in poor countries. Primary prevention has not been widely adopted due to health systems bar...
Analysis of germline alterations and testing patterns in Hispanic men with prostate cancer.
Authors: Justin Shaya, Lisa Madlensky, Frederick E. Millard, James Michael Randall, Tyler Francis Stewart, Archana Ajmera, Reena Cherry, Brent S. Rose, John Kellogg Parsons, Rana R. McKay
Journal: Journal of Clinical Oncology (2021)

Background: Little is known about the prevalence of germline alterations in Hispanic men with prostate cancer (PC). Here, we examine the rates of germline alterations in Hispanic men with PC, compare these rates to non-Hispanic white men, and examine factors associated with clinicians offering testing. Methods: Single center, retrospective analysis of patients (pts) with PC who self-identify as Hispanic and meet the NCCN criteria for germline testing. Pts who consented for testing underwent a commercial multigene germline assay. Among those tested, the proportion of pathogenic alterations and variants of uncertain significance (VUS) were computed in 20 genes associated with germline alterations in PC. This was compared to non-Hispanic white (NHW) pts who also underwent germline testing. Multivariate logistic regression was performed to assess clinical and demographic factors associated with clinicians offering germline testing and/or genetics referral. Results: We identified 136 Hispanic men with PC eligible for germline testing between 2018-2020. 26.1% (n=34) of pts underwent germline testing and among those tested, 14.7% (n=5/34) had a pathogenic alteration detected. Median age of the cohort was 70 years and 46.3% (n=63) had metastatic disease. Spanish was the primary language for 50% (n=68) and 14.0% (n=19) of pts had at least 1 first-degree relative with PC. Alterations were detected in ATM (n=2), CHEK2 (n=1), MSH2 (n=1), MSH6 (n=1). When stratified by disease status, the rate of pathogenic alterations was 7.7% (n=1/13) in localized and 19.0% (n=4/21) in metastatic disease. When compared to NHW pts who underwent testing (n=139), the rate of pathogenic alterations was not significantly different (14.7% in Hispanic vs 12.2% in NWH, p=0.77). The rate of VUS in Hispanic pts was significantly higher than NHW pts (20.6% in Hispanic vs 7.2% in NWH, p=0.047). In a multivariate model examining the factors associated with receipt of testing in Hispanic men (Table), the presence of metastatic disease and a family history of PC were positively associated with testing. Spanish as a primary language was negatively associated with testing. Age was not a significant predictor. Conclusions: Among Hispanic men who underwent germline testing, there was a similar rate of pathogenic germline alterations compared to NHW men. Among Hispanic men, primary Spanish speakers appear to have lower rates of germline testing. Bilingual strategies are needed to improve rates of testing to ensure equity in germline testing for all patients. [Table: see text]
Augmenting Tendon‐to‐Bone Repair with Functionally Graded Scaffolds
Authors: Chunlei Zhu, Jichuan Qiu, Stavros Thomopoulos, Younan Xia
Journal: Advanced Healthcare Materials (2021)

Tendon-to-bone repair often fails because the functionally graded attachment is not regenerated during the healing process. Biomimetic scaffolds that recapitulate the unique features of the native tendon-to-bone attachment hold great promise for enhancing the healing process. Among various types of scaffolds that are developed and evaluated for tendon-to-bone repair, those with gradations (in either a stratified or a continuous fashion) in composition, structure, mechanical properties, and cell phenotype have gained the most attention. In this progress report, the recent efforts in the rational design and fabrication of functionally graded scaffolds based upon electrospun nanofiber mats and inverse opal structures, as well as the evaluation of their applications in augmenting tendon-to-bone repair, are reviewed. This report concludes with perspectives on the necessary future steps for clinical translation of the scaffolds.
Maternal stress and depression are associated with respiratory phenotypes in urban children
Authors: Sima K. Ramratnam, Alexandre Lockhart, Cynthia M. Visness, Agustin Calatroni, Daniel J. Jackson, Peter J. Gergen, Leonard B. Bacharier, George T. O’Connor, Megan T. Sandel, Meyer Kattan, Robert A. Wood, James E. Gern
Journal: Journal of Allergy and Clinical Immunology (2021)
Academic careers and the COVID-19 pandemic: Reversing the tide
Authors: Rotonya M. Carr, Meghan B. Lane-Fall, Eugenia South, Donita Brady, Florence Momplaisir, Carmen E. Guerra, Diana Montoya-Williams, George Dalembert, Risa Lavizzo-Mourey, Roy Hamilton
Journal: Science Translational Medicine (2021)

The COVID-19 pandemic halted research operations at academic medical centers. This shutdown has adversely affected research infrastructure, the current research workforce, and the research pipeline. We discuss the impact of the pandemic on overall research operations, examine its disproportionate effect on underrepresented minority researchers, and provide concrete strategies to reverse these losses.
Derivation and Validation of a 4-Level Clinical Pretest Probability Score for Suspected Pulmonary Embolism to Safely Decrease Imaging Testing
Authors: Pierre-Marie Roy, Emilie Friou, Boris Germeau, Delphine Douillet, Jeffrey Allen Kline, Marc Righini, Grégoire Le Gal, Thomas Moumneh, Andrea Penaloza
Journal: JAMA Cardiology (2021)

In patients with suspected pulmonary embolism (PE), overuse of diagnostic imaging is an important point of concern.To derive and validate a 4-level pretest probability rule (4-Level Pulmonary Embolism Clinical Probability Score [4PEPS]) that makes it possible to rule out PE solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected PE.This study included consecutive outpatients suspected of having PE from US and European emergency departments. Individual data from 3 merged management studies (n = 11 114; overall prevalence of PE, 11%) were used for the derivation cohort and internal validation cohort. The external validation cohorts were taken from 2 independent studies, the first with a high PE prevalence (n = 1548; prevalence, 21.5%) and the second with a moderate PE prevalence (n = 1669; prevalence, 11.7%). A prior definition of pretest probability target values to achieve a posttest probability less than 2% was used on the basis of the negative likelihood ratios of D-dimer. Data were collected from January 2003 to April 2016, and data were analyzed from June 2018 to August 2019.The rate of PE diagnosed during the initial workup or during follow-up and the rate of imaging testing.Of the 5588 patients in the derivation cohort, 3441 (61.8%) were female, and the mean (SD) age was 52 (18.5) years. The 4PEPS comprises 13 clinical variables scored from -2 to 5. It results in the following strategy: (1) very low probability of PE if 4PEPS is less than 0: PE ruled out without testing; (2) low probability of PE if 4PEPS is 0 to 5: PE ruled out if D-dimer level is less than 1.0 μg/mL; (3) moderate probability of PE if 4PEPS is 6 to 12: PE ruled out if D-dimer level is less than the age-adjusted cutoff value; (4) high probability of PE if 4PEPS is greater than 12: PE ruled out by imaging without preceding D-dimer test. In the first and the second external validation cohorts, the area under the receiver operator characteristic curves were 0.79 (95% CI, 0.76 to 0.82) and 0.78 (95% CI, 0.74 to 0.81), respectively. The false-negative testing rates if the 4PEPS strategy had been applied were 0.71% (95% CI, 0.37 to 1.23) and 0.89% (95% CI, 0.53 to 1.49), respectively. The absolute reductions in imaging testing were -22% (95% CI, -26 to -19) and -19% (95% CI, -22 to -16) in the first and second external validation cohorts, respectively. The 4PEPS strategy compared favorably with all recent strategies in terms of imaging testing.The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected PE. It should now be tested in a formal outcome study.
Prevalence of microvascular angina among patients with stable symptoms in the absence of obstructive coronary artery disease: a systematic review
Authors: Elif Aribas, Jeanine E Roeters van Lennep, Suzette E Elias-Smale, Jan J Piek, Maurits Roos, Fariba Ahmadizar, Banafsheh Arshi, Dirk J Duncker, Yolande Appelman, Maryam Kavousi
Journal: Cardiovascular Research (2021)

Abstract Our purpose was to perform a systematic review to assess the prevalence of microvascular angina (MVA) among patients with stable symptoms in the absence of obstructive coronary artery disease (CAD). We performed a systematic review of the literature to group the prevalence of MVA, based on diagnostic pathways and modalities. We defined MVA using three definitions: (i) suspected MVA using non-invasive ischaemia tests; proportion of patients with non-obstructive CAD among patients with symptoms and a positive non-invasive ischaemia test result, (ii) suspected MVA using specific modalities for MVA; proportion of patients with evidence of impaired microvascular function among patients with symptoms and non-obstructive CAD, and (iii) definitive MVA; proportion of patients with positive ischaemia test results among patients with an objectified impaired microvascular dysfunction. We further examined the ratio of women-to-men for the different groups. Of the 4547 abstracts, 20 studies reported data on MVA prevalence. The median prevalence was 43% for suspected MVA using non-invasive ischaemia test, 28% for suspected MVA using specific modalities for MVA, and 30% for definitive MVA. Overall, more women were included in the studies reporting sex-specific data. The women-to-men ratio for included participants was 1.29. However, the average women-to-men ratio for the MVA cases was 2.50. In patients with stable symptoms of ischaemia in the absence of CAD, the prevalences of suspected and definitive MVA are substantial. The results of this study should warrant cardiologists to support, promote and facilitate the comprehensive evaluation of the coronary microcirculation for all patients with symptoms and non-obstructive CAD.