tbuckley/cabot-search huggingface dataset:
Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer
Authors: Abigail E Overacre-Delgoffe, Hannah J Bumgarner, Anthony R Cillo, Ansen H P Burr, Justin T Tometich, Amrita Bhattacharjee, Tullia C Bruno, Dario A A Vignali, Timothy W Hand
Journal: Immunity (2021)
Abstract 13177: Performance of Google Translate for Spanish Translations of Cardiac Care Unit Discharge Instructions
Authors: Angela Duvalyan, Vinayak Subramanian, Vicente Morales-Oyarvide, Bruno Álvarez Concejo, Andrew Sumarsono
Journal: Circulation (2021)

Introduction: Providing written discharge instructions (DIs) to non-English speaking patients is often challenging. Providers often must decide whether to write DIs in English or use online or in-person translation services. Prior studies evaluating the overall efficacy of Google Translate (GT) in the emergency department setting demonstrated mixed results, however the accuracy of GT for cardiology-specific diagnoses has not been studied. We evaluated the accuracy of GT for DIs for patients discharged from the inpatient cardiac care unit (CCU). Methods: We conducted a single-center, retrospective study of patients discharged from the CCU at Parkland Hospital. We extracted DIs along with the number of medication changes and procedures performed. We analyzed each sentence by content, Flesch-Kincaid Grade Level and Flesch-Kincaid Reading Ease formula. Using GT, we translated each sentence to Spanish and had two translators back-translate to English. The back-translated English was compared to the original English and graded for accuracy, meaning, fluency adequacy, and severity using a 5-point Likert Model. All scores were summed, with a maximum score of 20. We used univariate and multivariate logistic regressions to evaluate factors associated with perfect translation (score = 20). Results: Of the 44 DIs, 859 sentences were extracted. 769 (90%) of sentences were translated perfectly (score = 20) and 817 (95%) scored greater than or equal to 18. Thirty four sentences received a score of 3 or lower in any category. 2.6% (22 of 859) had severity scores of 3 or lower. In a multivariate logistic regression, sentence content of follow-up instructions was the only factor associated with higher risk of incorrect translation (OR 2.25, 95% CI: 1.05-4.84, P = 0.038), while Flesch-Kincaid Grade Level (95% CI: 0.97-1.05), Flesch-Kincaid Reading Ease (95% CI: 0.996 - 1.02), medication changes (95% CI: 0.93-1.04), and procedures performed (95% CI: 0.89-1.26) were not. Conclusion: GT perfectly translated 90% of DIs, but incorrectly translated 2.6% of instructions to a degree that may impair patient care. GT may be a useful tool to provide written DIs for cardiac care patients, but should still be used cautiously and in conjunction with verbal instructions.
Cancer associated-fibroblast-derived exosomes in cancer progression
Authors: Chao Li, Adilson Fonseca Teixeira, Hong-Jian Zhu, Peter ten Dijke
Journal: Molecular Cancer (2021)

To identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.
Initiation and feasibility of a multi-specialty minimally invasive surgical programme using a novel robotic system: A case series
Authors: Frances Dixon, Achal Khanna, Parveen Vitish-Sharma, Nidhi Shandil Singh, Kailash Nakade, Anjana Singh, Adnan Qureshi, Richard O’Hara, Barrie D. Keeler
Journal: International Journal of Surgery (2021)
Abstract 10510: Prognostic Value of the Combination of Cardiac MIBG Imaging and Serum Cholinesterase Level in Patients Admitted for Acute Decompensated Heart Failure
Authors: Yuto Tamura, Takahisa Yamada, Tetsuya Watanabe, Masahiro Seo, Takashi Morita, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Jun Nakamura, Kiyomi Kayama, Daisuke Sakamoto, KUMPEI UEDA, Takehiro Kogame, Takeshi Fujita, Keisuke Nishigaki, Yuto Fukuda, Yuki Kokubu, Masatake Fukunami
Journal: Circulation (2021)

Backgrounds: Cardiac MIBG imaging provides prognostic information in patients with acute decompensated heart failure (ADHF). On the other hand, serum cholinesterase (CHE) level, which reflect various factors such as hepatic function, inflammation and nutritional status, has been reported to be associated with poor outcome in ADHF patients. However, there is no information available on the prognostic value of the combination of cardiac MIBG imaging and CHE level in patients admitted for ADHF. Methods: We studied 579 consecutive patients admitted for ADHF. Cardiac MIBG imaging, echocardiography and venous blood sampling were performed just before discharge. The cardiac MIBG heart-to-mediastinum ratio (late HMR) was measured on the chest anterior view images obtained at 200 min after the isotope injection. The primary endpoint was cardiac event (CE) defined as unplanned heart failure hospitalization and cardiac death. Results: During a follow up period of 2.8±0.9 years, 196 patients reached the primary endpoint. On multivariate Cox analysis, late-HMR (p&lt;0.0001, HR 1.82 [1.34-2.47) and serum CHE level (p=0.047, HR 1.40 [1.01-1.94]) were significantly associated with CE after adjustment for age, sex, left ventricular ejection fraction, history of hypertension, diabetes mellitus, hemoglobin, blood urea nitrogen and albumin. Kaplan-Meier survival curve analysis demonstrated that patients with both low serum CHE level (&lt;217 U/L=median value) and late-HMR (&lt;1.66=median value) had a significantly increased risk of CE in than those either or none of them. Conclusion: The combination of cardiac MIBG imaging and serum CHE level would be useful for stratifying ADHF patients at risk for cardiac events.
Clinical Application of an Ex-Vivo Platform to Guide the Choice of Drug Combinations in Relapsed/Refractory Lymphoma; A Prospective Study
Authors: Sanjay De Mel, Jasmine Goh, Masturah Rashid, Michal Hoppe, Xi Yun Zhang, Patrick Jaynes, Esther KY Ng, Nur Atiqa Diana Binte Rahmat, Xin Liu, Michelle Poon, Hian Li Esther Chan, Joanne Lee, Yen-Lin Chee, Liang Piu Koh, Lip Kun Tan, Teck Guan Soh, Yi Ching Yuen, Hoi Yin Loi, Siok Bian Ng, Xueying Goh, Daryl Tan, Daryl Ming Zhe Cheah, Wan Lu Pang, Dachuan Huang, Nagavalli Somasundaram, Tiffany Tang, Jason Yongsheng Chan, Soon Thye Lim, Choon Kiat Ong, Wee Joo Chng, Edward KH Chow, Anand Jeyasekharan
Journal: Blood (2021)
Reduced-Intensity Therapy with Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) Yields Durable Remissions in Adults with Newly-Diagnosed Acute Lymphoblastic Leukemia/Lymphoma (ALL): Final Results of a Phase II Trial
Authors: Ryan D. Cassaday, Kelsey-Leigh A. Garcia, Olga Sala-Torra, Philip A. Stevenson, Christen H. Martino, Yajuan J. Liu, Min Fang, Mary-Elizabeth M. Percival, Anna B. Halpern, Pamela S. Becker, Vivian G. Oehler, Andrei R Shustov, Jason P. Cooper, Johnnie J. Orozco, Paul C. Hendrie, Roland B. Walter, Jerry P. Radich, Lorinda A. Soma, Elihu H. Estey
Journal: Blood (2021)
When I use a word . . . . No jab, no job? A benefit:harm balance analysis
Authors: Jeffrey K Aronson
Journal: BMJ (2021)

The current debate about whether individuals should be entitled to work in the healthcare sector if they decline to be vaccinated against SARS-CoV2 has been largely informed by personal opinions and argument by analogy. A benefit:harm balance analysis suggests that while vaccination has a highly favourable benefit:harm balance, the balance in instituting a "no jab, no job" policy is highly uncertain and may be unfavourable. Furthermore, there are practical difficulties and legal uncertainties. The much misunderstood precautionary principle dictates that if the benefit:harm balance of an intervention is unclear and may be unfavourable, the intervention should not be undertaken. Furthermore, the onus is on those who believe that the benefit:harm balance will be favourable to prove that it is so; it is not for the sceptics to prove that it isn't. In the absence of good evidence in favour, this is an intervention that would be best avoided.
Abstract 13222: Genetic Variants Close to <i>NKX2-5</i> and <i>MYH6</i> Are Associated With AV Nodal Reentry Tachycardia in First Genome-Wide Association Study
Authors: Laura Andreasen, Gustav Ahlberg, Pia Rengtved Lundegaard, Hildur Ægisdottir, Jacob Peter Hartmann, Christian Paludan-Mueller, Katra Hadji-Turdeghal, Jonas Ghouse, Steen Pehrson, Henrik Jensen, Sam Riahi, Jim Hansen, Niels Sandgaard, stig Haunso, Jorgen Kanters, Christina Ellervik, Henning Bundgaard, Henrik Ullum, Hilma Holm, David Arnar, Jesper Hastrup Svendsen, Morten Olesen
Journal: Circulation (2021)

Introduction: AV nodal re-entry tachycardia (AVNRT) is the most common type of paroxysmal supraventricular tachycardia. At present, the underlying etiology of AVNRT is unclear. Hypothesis: In a genome-wide association study (GWAS), we aimed to identify common genetic variants associated with AVNRT. Methods: We performed a GWAS meta-analysis of Danish patients diagnosed with AVNRT verified by invasive electrophysiological study. An Icelandic population of AVNRT patients was used for replication. We performed conditional analysis by adjusting our analysis for atrial fibrillation (AF) genetics and transcriptome-wide analyses (TWAS) to assess associations between gene expression and AVNRT. Electrophysiological consequences were investigated in CRISPR-Cas9 modified zebrafish. Results: A total of 1,515 AVNRT patients and 38,428 controls were available for meta-analysis. Two genetic loci associated with AVNRT; at chromosome 5q35.1, close to the NKX2-5 gene (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.38-1.58, P = 2.6 х 10 -13 ), and at 14q11.2 in the MYH6 gene (OR 1.26, 95% CI 1.18-1.34, P = 2.3 х 10 -8 ). We found similar effect sizes and direction of effect for both loci in the Icelandic AVNRT cohort. Using conditional analyses, we found that these loci were associated with AVNRT independent of AF. Analyses of loss of Nkx2-5 zebrafish showed no difference with regards to electrocardiographic parameters and transmission electron microscopy of atrial tissue compared with wildtype. Conclusion: This is, to our knowledge, the first GWAS on AVNRT. We identified two genetic loci that associated with AVNRT.
Abstract MP235: PROX1 Contributes To Cardiac Valve Disease
Authors: YenChun Ho, Xin Geng, Rohan Varshney, Jang Kim, Sandeep Surbrahmanian, Zahra Alvandi, Lijuan Chen, Fumio Matsuzaki, Elena Aikawa, Lorin Olson, Jasimuddin Ahamed, Joyce E Bischoff, Sathish Srinivasan
Journal: Circulation Research (2021)

Background: Heart valves regulate the unidirectional forward flow and prevent retrograde backflow of blood during the cardiac cycle. Cardiac valve disease (CVD) is observed in approximately 2.5% of the general population and the incidence increases to ~10% in elderly people. Patients with severe CVD require surgery and effective pharmacological treatments are currently not available. PROX1 is a transcription factor that regulates the development of lymphatic, venous, and lymphovenous valves (vascular valves). We identified that PROX1 is also expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 regulates cardiac valve development and disease is not known. Method and Results: We have discovered that mice lacking Prox1 in their VECs ( Prox1 ΔVEC ) develop enlarged aortic and mitral valves in which the expression of proteoglycans is increased (control, N=10; Prox1 ΔVEC , N=9, p &lt;0.05). Echocardiography revealed moderate to severe stenosis of aortic valves of Prox1 ΔVEC mice (control, N=5; Prox1 ΔVEC , N=9, p &lt;0.05). PROX1 regulates the expression of the transcription factor FOXC2 in the vascular valves. Similarly, we have found that the expression of FOXC2 is downregulated in the VECs of Prox1 ΔVEC mice. Specific knockdown of FOXC2 in VECs results in the thickening of aortic valves (control, N=10; shFoxc2 ΔVEC , N=8, p &lt;0.05). Furthermore, restoration of FOXC2 expression in VECs ( Foxc2 OE-VEC ) ameliorates the thickening of the aortic valves of Prox1 ΔVEC mice ( Prox1 ΔVEC , N=9; Foxc2 OE-VEC ; Prox1 ΔVEC , N=8, p &lt;0.05). We have also determined that the expression of platelet-derived growth factor-B ( Pdgfb ) is increased in the valve tissue of Prox1 ΔVEC mice and in PROX1 deficient sheep mitral valve VECs (MVECs) (siCtrl , N=4; siProx1 , N=4, p &lt;0.05). Additionally, hyperactivation of PDGF-B signaling in mice results in a phenotype that is similar to Prox1 ΔVEC mice (control , N=4; Pdgfb GOF , N=3, p &lt;0.05). Conclusion: Together these data suggest that PROX1 maintains the extracellular matrix composition of cardiac valves by regulating the expressions of FOXC2 and PDGF-B in VECs.
A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients
Authors: Chuan Li, Yee Peng Phoon, Keaton Karlinsey, Ye F. Tian, Samjhana Thapaliya, Angkana Thongkum, Lili Qu, Alyssa Joyce Matz, Mark Cameron, Cheryl Cameron, Antoine Menoret, Pauline Funchain, Jung-Min Song, C. Marcela Diaz-Montero, Banumathi Tamilselvan, Jackelyn B. Golden, Michael Cartwright, Annabelle Rodriguez, Christopher Bonin, Anthony Vella, Beiyan Zhou, Brian R. Gastman
Journal: The Journal of Experimental Medicine (2021)

Immune checkpoint inhibitor (ICI) therapy continues to revolutionize melanoma treatment, but only a subset of patients respond. Major efforts are underway to develop minimally invasive predictive assays of ICI response. Using single-cell transcriptomics, we discovered a unique CD8 T cell blood/tumor-shared subpopulation in melanoma patients with high levels of oxidative phosphorylation (OXPHOS), the ectonucleotidases CD38 and CD39, and both exhaustion and cytotoxicity markers. We called this population with high levels of OXPHOS “CD8+ TOXPHOS cells.” We validated that higher levels of OXPHOS in tumor- and peripheral blood–derived CD8+ TOXPHOS cells correlated with ICI resistance in melanoma patients. We then developed an ICI therapy response predictive model using a transcriptomic profile of CD8+ TOXPHOS cells. This model is capable of discerning responders from nonresponders using either tumor or peripheral blood CD8 T cells with high accuracy in multiple validation cohorts. In sum, CD8+ TOXPHOS cells represent a critical immune population to assess ICI response with the potential to be a new target to improve outcomes in melanoma patients.
QOLP-22. THE PSYCHO-ONCOLOGICAL BURDEN OF PATIENTS WITH AGGRESSIVE MENINGIOMA – RESULTS FROM A RETROSPECTIVE CROSS-SECTIONAL STUDY
Authors: Christine Jungk, Madlen Raedel, Julia Mattern-Tremper, Rolf Warta, Christel Herold-Mende, Andreas Unterberg
Journal: Neuro-Oncology (2021)

Abstract Despite the perception of meningioma as a benign disease, up to 35% of patients experience a clinically aggressive course with debilitating treatment and poor outcome. In contrast to the growing interest in novel therapies, the impact on health-related quality of life (HRQoL) is still understudied. Here, we analysed the psycho-oncological burden of patients with aggressive meningioma. Our institutional cohort was searched for meningioma patients with surgery as first intervention and HRQoL was assessed retrospectively at one time point with standardized self-assessment questionnaires (HADS-D, EORTC-QLQ-C30). Aggressive meningioma was defined as WHO grade 2 or 3 or recurrence of a WHO grade 1 meningioma within 5 years after index surgery. Results were correlated with demographic, tumor- and treatment-related factors by multivariate linear regression and compared to internal control patients (WHO grade 1 meningioma, no recurrence within the first 5 years). 400 out of 653 patients returned the questionnaires (62%). Of those, 95 patients (24%) were classified as aggressive meningioma while 305 patients served as internal control. Patients with and without aggressive meningioma differed with regard to sex (p=0.019), age (p=0.015), extent of resection (p&amp;lt; 0.0001) and adjuvant radiotherapy (p&amp;lt; 0.0001) at index surgery and KPS at 1st follow-up (p=0.037). 34% and 24% of aggressive meningioma patients were screened positive on the anxiety and depression subscales of HADS-D as opposed to 33% and 23% of internal controls (not significant). Aggressive meningioma patients fared significantly worse on most of the function scales of QLQ-C30 (QL: p=0.004; PF: p=0.049; RF: p=0.003; CF: p=0.01; SF: p=0.018) and reported more financial difficulties (FI: p=0.015). In multivariate regression analysis, female sex, KPS at 1st follow-up &amp;lt; 70 and aggressive meningioma were independent factors of impaired HRQoL. This cross-sectional analysis demonstrates that HRQoL is impaired in aggressive meningioma patients who should be screened and treated for their psycho-oncological needs.
Abstract 11726: Impact of Digoxin Use on Doses of First-Line Agents Used in Heart Failure
Authors: Hani Hamade, Ahmad Jabri, Mohamed Farhan Nasser, Kathir Balakumaran
Journal: Circulation (2021)

Introduction: Digoxin was one of the first agents used in the management of heart failure with reduced ejection fraction (HFrEF). Concerns over its safety, efficacy and the introduction of guideline-directed medical therapy (GDMT) has relegated it to a secondary role. The effects of digoxin are still under debate, and its use in patients on GDMT remains unclear. Hypothesis: Patients with HFrEF on digoxin can tolerate higher doses of beta blocker and angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI). Methods: A retrospective chart review was performed on 233 patients with HFrEF managed at a tertiary care center in Cleveland, Ohio. A bivariate analysis was performed to compare patients on digoxin with patients not on digoxin in terms of ability to progress the dosing of beta blocker and ACEI/ARB/ARNI. Results: Cases and controls were similar in age, gender, height, weight, ethnicity, and no significant differences were noted when comparing baseline comorbidities and biochemical testing (Table 1). There was no significant difference between the two groups in terms of patients receiving higher doses of beta-blockers (p=0.34), ACEI (p=0.33), ARB (p=0.57), or ARNI (0.65). Stacked column charts showing the differences in dosing between the groups for all four categories are displayed in Figure 1. Conclusions: There was no significant difference between the doses of beta blocker, ACEI, ARB or ARNI among HFrEF patients on digoxin compared to those that were not. From these results, we conclude that digoxin use may not significantly affect the ability to increase the doses of GDMT in patients with HFrEF.
Vaccines, therapeutics, and diagnostics for covid-19: redesigning systems to improve pandemic response
Authors: Rohit Ramchandani, Michel Kazatchkine, Joanne Liu, Preeti Sudan, Mark Dybul, Precious Matsoso, Anders Nordström, Alexandra Phelan, Helena Legido-Quigley, Sudhvir Singh, Shunsuke Mabuchi
Journal: BMJ (2021)

Vaccines, therapeutics, and diagnostics for covid-19: redesigning systems to improve pandemic responseRohit Ramchandani and colleagues propose a framework to ensure essential public health tools are fairly distributed in future pandemics V accines, therapeutics, and diagnostics are key public health tools for controlling the covid-19 pandemic, yet many countries, particularly low and middle income countries (LMICs), have had inadequate access.Many have yet to determine, for example, when and where they will be getting their vaccines from, and only 3% of people in low income countries had received at least one dose by October 2021. 1 The Access to COVID -19 Tools Accelerator (ACT-A) is a multilateral coordination mechanism set up to accelerate development, production, and equitable access to covid-19 tests, treatments, and vaccines globally.The concept brings together governments, scientists, businesses, civil society, philanthropists and global health organisations.Despite its bold vision, ACT-A has thus far fallen short of its • Agreements around technology transfer and intellectual property licensing, regional trial networks, inclusive governance, and substantial predictable financing are essential
Clinical Study on the CD19-Targeted Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Acute Lymphoblast Leukemia: A Single Center of Real World Data
Authors: Jing Huang, Zhi Liu, Ruiming Ou, Liling Zheng, Yangmin Zhu, Yuanyuan Du, Qinjun Zhou, Jia Fei, Shuang Liu, Qing Zhang
Journal: Blood (2021)