tbuckley/cabot-search huggingface dataset:
NK cells enhance CAR-T cell antitumor efficacy by enhancing immune/tumor cells cluster formation and improving CAR-T cell fitness
Authors: Mireia Bachiller, Lorena Perez-Amill, Anthony Matthew Battram, Sebastian Ciro Carné, Amer Najjar, Els Verhoeyen, Manel Juan, Alvaro Urbano-Ispizua, Beatriz Martin-Antonio
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Chimeric antigen receptor (CAR)-T cell immunotherapy has modified the concept of treatment in hematological malignancies. In comparison with pediatric patients, where responses are maintained over many years, older patients, such as those with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM), present lower persistence of CAR-T cells that might be due to decreased fitness of T cells acquired with aging. Moreover, cord blood derived-NK cells (CB-NKs) and CAR-NK cells derived from CB-NK can be used ‘off-the-shelf’ as immune cells with antitumor properties for the treatment of cancer patients. However, to date, clinical studies have only demonstrated the safety of these therapies but not optimal efficacy. To confront the shortcomings of each therapy, we devised a novel approach consisting of simultaneous (CAR-)NK cell and CAR-T cell administration. In this setting, NK cells demonstrate an important immunoregulation of T cells that could be exploited to enhance the efficacy of CAR-T cells. Methods A combinatorial treatment based on either CAR-T and CAR-NK cells or CB-NK and CAR-T cells in two models of NHL and MM was performed. Antitumor efficacy was analyzed in vitro and in vivo, and parameters related to early activation, exhaustion and senescence of T cells were analyzed. Results We show that CAR-NK cells derived from CB-NK are only effective at high doses (high E:T ratio) and that their activity rapidly decreases over time in comparison with CAR-T cells. In comparison and to exploit the potential of ‘off-the-shelf’ CB-NK, we demonstrate that a low number of CB-NK in the CAR-T cell product promotes an early activation of CAR-T cells and their migration to MM cells leading to enhanced anti-MM efficacy. Moreover, cytokines related to CRS development were not increased, and importantly, CB-NK enhanced the fitness of both CAR pos and CAR neg T cells, promoting lower levels of exhaustion and senescence. Conclusion This study demonstrates a relevant immunoregulatory role of CB-NK collaborating with CAR-T cells to enhance their antitumor activity. A novel and different approach to consider in CAR-T cell immunotherapy studies is presented here with the goal to enhance the efficacy of the treatment.
A new preparative regimen for older patients with aggressive CD20-positive B-cell lymphoma utilizing standard dose yttrium-90 ibritumomab tiuxetan (Zevalin) radioimmunotherapy (RIT) combined with high-dose BEAM followed by autologous hematopoietic cell transplantation (AHCT) : Targeted intensification without increased transplant-related toxicity
Authors: Hc Fung
Journal: Blood (2003)
28551 IMAPSORS project: A multicenter validation study to assess the accuracy of an artificial intelligence solution to quantify psoriasis severity
Authors: Antonio Martorell, Eduardo Ibor Crespo, Victor Gisbert Climent, Salvador Arias, Ricardo Ruiz-Villaverde, Rosa Taberner, Antonio Sahuquillo, Maria Luisa Fernandez-Diaz
Journal: Journal of the American Academy of Dermatology (2021)
Facilitators Associated With Building and Sustaining Therapeutic Alliance in Advanced Pediatric Cancer
Authors: Erica C. Kaye, Sarah Rockwell, Cameka Woods, Monica E. Lemmon, Karen Andes, Justin N. Baker, Jennifer W. Mack
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Therapeutic alliance is a core component of patient- and family-centered care, particularly in the setting of advancing cancer. Communication approaches used by pediatric oncologists to foster therapeutic alliance with children with cancer and their families are not well understood. <h3>Objectives</h3> To identify key oncologist-driven facilitators associated with building and sustaining therapeutic alliance in the setting of advancing pediatric cancer and to develop a framework to guide clinical practice and future investigation of therapeutic alliance. <h3>Design, Setting, and Participants</h3> In this qualitative study, serial disease reevaluation discussions that occurred in the clinic, inpatient hospital, or off campus via telephone were recorded among pediatric oncologists, patients with high-risk cancer, and their families across 24 months or until death, whichever occurred first, from 2016 to 2020. This analysis focused on recorded discussions for pediatric patients who experienced progressive disease during the study period. Content analysis was conducted across recorded dialogue to derive inductive codes and identify themes. Participants were patient-parent dyads for whom a primary oncologist projected the patient's survival to be 50% or less, all family members and friends who attended any of their recorded disease reevaluation conversations, and their oncologists and other clinicians who attended the recorded discussions. <h3>Results</h3> A total of 33 patient-parent dyads were enrolled and followed longitudinally. From this cohort, 17 patients experienced disease progression during the study period, most of whom were female (11 [64.7%]) and White (15 [88.2%]) individuals. For these patients, 141 disease reevaluation discussions were audio recorded, comprising 2400 minutes of medical dialogue. Most children (14 [82.4%]) died during the study period. A median of 7 disease reevaluation discussions per patient (range, 1-19) were recorded. Content analysis yielded 28 unique concepts associated with therapeutic alliance fostered by oncologist communication. Ultimately, 7 core themes emerged to support a framework for clinician approaches associated with optimizing therapeutic alliance: human connection, empathy, presence, partnering, inclusivity, humor, and honesty. <h3>Conclusions and Relevance</h3> In this qualitative study, pediatric oncologists used diverse communication approaches associated with building and deepening connections across advancing illness. These findings offer a framework to support clinical and research strategies for strengthening therapeutic alliance among pediatric oncologists, patients, and families.
Annual Tuberculosis Preventive Therapy for Persons With HIV Infection
Authors: Gavin Churchyard, Vicky Cárdenas, Violet Chihota, Kathy Mngadi, Modulakgotla Sebe, William Brumskine, Neil Martinson, Getnet Yimer, Shu-Hua Wang, Alberto L. Garcia-Basteiro, Dinis Nguenha, LeeAnne Masilela, Zainab Waggie, Susan van den Hof, Salome Charalambous, Frank Cobelens, Richard E. Chaisson, Alison D. Grant, Katherine L. Fielding
Journal: Annals of Internal Medicine (2021)

Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain.To compare treatment completion rates of weekly isoniazid-rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine-isoniazid regimen given annually for 2 years versus once.Randomized trial. (ClinicalTrials.gov: NCT02980016).South Africa, Ethiopia, and Mozambique.Persons with HIV infection who were receiving antiretroviral therapy, were aged 2 years or older, and did not have active tuberculosis.Participants were randomly assigned to receive weekly rifapentine-isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24 using chest radiography and sputum culture.Treatment completion was assessed using pill counts. Tuberculosis incidence was measured over 24 months.Between November 2016 and November 2017, 4027 participants were enrolled; 4014 were included in the analyses (median age, 41 years; 69.5% women; all using antiretroviral therapy). Treatment completion in the first year for the combined rifapentine-isoniazid groups (n = 3610) was 90.4% versus 50.5% for the isoniazid group (n = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine-isoniazid regimen twice (n = 1808) or once (n = 1802) was similar (hazard ratio, 0.96 [CI, 0.61 to 1.50]).If rifapentine-isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness.Treatment completion was higher with rifapentine-isoniazid for 3 months compared with isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of preventive therapy did not provide additional benefit to persons receiving antiretroviral therapy.The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation.
Data Quality, Data Sharing, and Moving Artificial Intelligence Forward
Authors: Joann G. Elmore, Christoph I. Lee
Journal: JAMA Network Open (2021)

Mateusz Buda, MSc; Ashirbani Saha, PhD; Ruth Walsh, MD; Sujata Ghate, MD; Nianyi Li, PhD; Albert Święcicki, BSc; Joseph Y. Lo, PhD; Maciej A. Mazurowski, PhD
Use of an Analytics and Electronic Health Record–Based Approach for Targeted COVID-19 Vaccine Outreach to Marginalized Populations
Authors: Jacob Stein, Megan Fasold, Karyn Jean Daguerre, Jaime Richardson, Summer Cheek, Marjory Charlot, Ethan Basch
Journal: JAMA Oncology (2021)

were men.We observed significant differences between the enrollment of sexes across all trial phases and tumor types except thyroid (Table ).Drug trials for colon and kidney cancer enrolled the least number of women, with 33% participation rates (Figure).Comparing 2000 to 2010 with 2011 to 2020, we observed a marginal increase in female participation, from 40% to 42%, respectively (P < .001).We evaluated the association between industry and NIH-sponsored studies in the US (n = 358) and found that NIH-funded trials enrolled a higher proportion of women (48%) compared with industry trials (41%) (P < .001).Discussion | It is essential that women be enrolled in clinical trials in numbers that, at least, mirror the distribution of the disease in the population so that potential biological differences can be understood.Our analysis, although limited to 6 tumor types, suggests that sex differences persist in clinical trials.In 2020, women represented 77% of newly diagnosed thyroid cancer cases worldwide 6 yet comprised only 51% of participants in trials investigating thyroid drugs (Figure).Similarly, women represented 48% of global colon cancer cases 6 yet accounted for only 33% of trial participants for colon cancer therapeutics (Figure).Higher enrollment of women in NIH-funded studies (48%) compared with industry studies (41%) warrants further exploration, but the stagnant rates of women in trials suggest that regulatory initiatives 2 over the past 2 decades may be insufficient.Our analysis, although limited to sponsor-and manufacturer-disclosed information, demonstrates that persistent inequities
Implementing and Enhancing Multifaceted Systems Interventions to Improve Goals-of-Care Discussions Among Patients With Serious Illness—An Opportunity for Human-Centered Design
Authors: Nauzley C. Abedini, J. Randall Curtis
Journal: JAMA Network Open (2021)

Andrew Lagrotteria, MSc; Marilyn Swinton, MSc; Jessica Simon, MBChB; Seema King, MSc, MSW; Gwenn Boryski, BBS; Irene Wai Yan Ma, MD, PhD; Fiona Dunne, MD; Japteg Singh, MSc, MPH; Rachelle E. Bernacki, MD, MS; John J. You, MD, MSc
Wilms Tumor (Nephroblastoma), Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
Authors: Frank Balis, Daniel M. Green, Clarke Anderson, Shelly Cook, Jasreman Dhillon, Kenneth Gow, Susan Hiniker, Rama Jasty-Rao, Chi Lin, Harold Lovvorn, Iain MacEwan, Julian Martinez-Agosto, Elizabeth Mullen, Erin S. Murphy, Mark Ranalli, Daniel Rhee, Denise Rokitka, Elisabeth (Lisa) Tracy, Tamara Vern-Gross, Michael F. Walsh, Amy Walz, Jonathan Wickiser, Matthew Zapala, Ryan A. Berardi, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCCN Guidelines for Wilms Tumor focus on the screening, diagnosis, staging, treatment, and management of Wilms tumor (WT, also known as nephroblastoma). WT is the most common primary renal tumor in children. Five-year survival is more than 90% for children with all stages of favorable histology WT who receive appropriate treatment. All patients with WT should be managed by a multidisciplinary team with experience in managing renal tumors; consulting a pediatric oncologist is strongly encouraged. Treatment of WT includes surgery, neoadjuvant or adjuvant chemotherapy, and radiation therapy (RT) if needed. Careful use of available therapies is necessary to maximize cure and minimize long-term toxicities. This article discusses the NCCN Guidelines recommendations for favorable histology WT.
BT14: Exploring the feasibility of a remote acne service: a report of a pilot study using the MySkinSelfie platform during the COVID‐19 pandemic
Journal: British Journal of Dermatology (2021)

that sufficient information was provided throughout the pathway and were happy to engage with this service should they require a similar procedure in the future.In this cohort of patients, their first visit to hospital was for a procedure.There are many benefits in reducing F2F hospital attendances.As well as reducing footfall during the pandemic, there is less lost work time and cost of travel for patients or their relatives, more efficient use of hospital facilities and reduced carbon footprint.Our survey suggests that preoperative telephone consultations are liked by patients and appropriate in meeting the requirements of Montgomery consent for a teledermatology service.
前糖尿病肥満における血管機能を損なう内皮細胞の不均一性とネットワーク構成の破壊【JST・京大機械翻訳】
Authors: Wilson Calum, Zhang Xun, D Lee Matthew, MacDonald Margaret, R Heathcote Helen, M N Alorfi Nasser, Buckley Charlotte, Dolan Sharron, G McCarron John
Journal: Metabolism (2020)
Protection of Renal Function During Surgery of the Abdominal Aorta
Authors: R J BAIRD, W B FIROR, H W BARR
Journal: JAMA (1963)

The operative and postoperative urinary output of 55 patients who underwent surgery for ruptured abdominal aortic aneurysms, unruptured abdominal aortic aneurysms, and aorto-iliac occlusive disease was recorded. There were five cases of postoperative anuria among 28 patients who received no free fluid in the immediate preoperative period. No case of anuria occurred in 27 patients who received either: (1) a water load of 5% dextrose in water or (2) 20% mannitol solution. The patients who received mannitol had a markedly greater operative and postoperative urinary output.Intravenous infusion of mannitol is recommended during the preoperative and operative period in patients with ruptured aneurysms of the abdominal aorta.
DNA methylation of HOX genes in leukemia and myeloproliferative disorders
Authors: Jaroslav Jelinek, Vazganush Gharibyan, Rong He, Amanda Saraf, Samantha Lau, Josef Prchal, Jean-Pierre Issa
Journal: Cancer Research (2007)

235  The HOX gene family consists of 39 genes organized in 4 clusters A-D on 4 chromosomes in 13 paralogous groups. These genes regulate developmental processes and tissue differentiation. HOX gene translocations are frequently found in leukemia. DNA methylation of CpG islands surrounding transcriptional start sites (TSS) of genes results in transcriptional silencing. Epigenetic methylation marks are permanent and functionally equivalent to loss-of-function mutations. Most HOX genes have CpG islands at their TSS. Silencing of HOX genes by DNA methylation may disrupt normal development of blood cells and thus be involved in leukemic transformation. We performed comprehensive DNA methylation analyses of 31 HOX genes with CpG islands in TSS regions (HOXA1, 4, 5, 6, 7, 9, 10a, 10b, 11 and 13; HOXB1, 4, 5, 7, 8, 9, and 13; HOXC4, 5, 8, 9, 10, 11, and 13; HOXD1, 4, 8, 9, 10, 11, and 13). We analyzed DNA in blood cells from 20 chronic myelogenous leukemia (CML), 6 polycythemia vera (PV), 24 acute myeloid leukemia (AML), and 20 acute lymphoblastic leukemia (ALL) patients, comparing the results with 25 normal controls. We used bisulfite pyrosequencing to quantitate levels of cytosine methylation in CpG islands at TSS. Statistical analyses were performed with nonparametric tests. Asterisks (*) denote statistically significant methylation differences from normal controls (p
Nanovaccine biomineralization for cancer immunotherapy: a NADPH oxidase‐inspired strategy for improving antigen cross-presentation via lipid peroxidation
Authors: Runping Su, Gaowei Chong, Haiqing Dong, Jingjing Gu, Jie Zang, Ruiqing He, Juanjuan Sun, Tingting Zhang, Yuge Zhao, Xiao Zheng, Yan Yang, Yan Li, Yongyong Li
Journal: Biomaterials (2021)
Circular RNA CircEYA3 induces energy production to promote pancreatic ductal adenocarcinoma progression through the miR-1294/c-Myc axis
Authors: Zeyin Rong, Si Shi, Zhen Tan, Jin Xu, Qingcai Meng, Jie Hua, Jiang Liu, Bo Zhang, Wei Wang, Xianjun Yu, Chen Liang
Journal: Molecular Cancer (2021)

Extensive studies have demonstrated the pivotal roles of circular RNAs (circRNAs) in the occurrence and development of different human cancers. However, the expression and regulatory roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear.CircEYA3 was explored based on Gene Expression Omnibus (GEO) dataset analysis. qRT-PCR was applied to determine the expression of circRNAs, miRNAs and mRNAs in PDAC cells and tissues. The biological roles of circEYA3 in vitro and in vivo were determined by performing a series of functional experiments. Further, dual luciferase reporter, fluorescence in situ hybridization (FISH), RNA pull-down assays, and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of circEYA3 with miR-1294.CircEYA3 was elevated in PDAC tissues and cells, and a higher level of circEYA3 was significantly associated with a poorer prognosis in patients with PDAC. Functionally, circEYA3 increased energy production via ATP synthesis to promote PDAC progression in vitro and in vivo. Mechanistically, circEYA3 functions as an endogenous miR-1294 sponge to elevate c-Myc expression, thus exerting its oncogenic functions.CircEYA3 promotes the progression of PDAC through the miR-1294/c-Myc signalling axis, and circEYA3 may be an efficient molecular therapeutic target in PDAC.
Long-Term Prognostic Value of Stress CMR in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Théo Pezel, Thomas Hovasse, Francesca Sanguineti, Marine Kinnel, Philippe Garot, Stéphane Champagne, Solenn Toupin, Thierry Unterseeh, Jérôme Garot
Journal: JACC. Cardiovascular imaging (2021)
Long Noncoding RNAs and Human Liver Disease
Authors: Johanna K. DiStefano, Glenn S. Gerhard
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions about their potential biological significance and roles in human health and disease. Technological and computational advances have enabled functional annotation of a large number of lncRNAs. Though the number of publications related to lncRNAs has escalated in recent years, relatively few have focused on those involved in hepatic physiology and pathology. We provide an overview of evolving lncRNA classification systems and characteristics and highlight important advances in our understanding of the contribution of lncRNAs to liver disease, with a focus on nonalcoholic steatohepatitis, hepatocellular carcinoma, and cholestatic liver disease.
mTORC1 Promotes ARID1A Degradation and Oncogenic Chromatin Remodeling in Hepatocellular Carcinoma
Authors: Shanshan Zhang, Yu-Feng Zhou, Jian Cao, Stephen K. Burley, Hui-Yun Wang, X.F. Steven Zheng
Journal: Cancer Research (2021)

The SWI/SNF chromatin remodeling complexes control accessibility of chromatin to transcriptional and coregulatory machineries. Chromatin remodeling plays important roles in normal physiology and diseases, particularly cancer. The ARID1A-containing SWI/SNF complex is commonly mutated and thought to be a key tumor suppressor in hepatocellular carcinoma (HCC), but its regulation in response to oncogenic signals remains poorly understood. mTOR is a conserved central controller of cell growth and an oncogenic driver of HCC. Remarkably, cancer mutations in mTOR and SWI/SNF complex are mutually exclusive in human HCC tumors, suggesting that they share a common oncogenic function. Here, we report that mTOR complex 1 (mTORC1) interact with ARID1A and regulates ubiquitination and proteasomal degradation of ARID1A protein. The mTORC1-ARID1A axis promoted oncogenic chromatin remodeling and YAP-dependent transcription, thereby enhancing liver cancer cell growth in vitro and tumor development in vivo. Conversely, excessive ARID1A expression counteracted AKT-driven liver tumorigenesis in vivo. Moreover, dysregulation of this axis conferred resistance to mTOR-targeted therapies. These findings demonstrate that the ARID1A-SWI/SNF complex is a regulatory target for oncogenic mTOR signaling, which is important for mTORC1-driven hepatocarcinogenesis, with implications for therapeutic interventions in HCC. SIGNIFICANCE: mTOR promotes oncogenic chromatin remodeling by controlling ARID1A degradation, which is important for liver tumorigenesis and response to mTOR- and YAP-targeted therapies in hepatocellular carcinoma.See related commentary by Pease and Fernandez-Zapico, p. 5608.
25726 Prospective adjuvant therapy trial design using a prognostic 40-gene expression profile (40-GEP) test for high-risk cutaneous squamous cell carcinoma (cSCC) and BWH staging-based risk assessment
Authors: Sherrif F. Ibrahim, Sarah T. Arron, Ally-Khan Somani, Sarah J. Kurley, Kyle R. Covington, Alison L. Fitzgerald, Chrysalyne D. Schmults, Ashley Wysong
Journal: Journal of the American Academy of Dermatology (2021)
Use of Antibiotics during Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Hepatocellular Carcinoma
Authors: Ka Shing Cheung, Lok Ka Lam, Wai Kay Seto, Wai K. Leung
Journal: Liver Cancer (2021)

Recent studies suggested that use of antibiotics may interfere with treatment responses to immune checkpoint inhibitors (ICIs). We determined whether concurrent use of antibiotics during ICI therapy was associated with adverse outcomes in patients with advanced hepatocellular carcinoma (HCC).This is a territory-wide retrospective cohort study including all advanced HCC patients who received ICIs (nivolumab, pembrolizumab, or ipilimumab) between January 2014 and December 2019. Exclusion criteria included prior liver transplantation and use of cabozantinib, regorafenib, or ramucirumab. The exposure of interest was concurrent antibiotic use within 30 days before or after the commencement of ICI. The adjusted hazard ratio (aHR) of cancer-related mortality and all-cause mortality with antibiotic use was derived by propensity score (PS) matching in 1:2 ratio of covariates including baseline characteristics, causes of cirrhosis, Child-Pugh status, prior HCC treatment, comorbidities, concurrent medications, and laboratory results including alpha fetoprotein.A total of 395 HCC patients who had received ICIs were included. During a median follow-up of 16.5 months (interquartile range [IQR]: 5.6-44.3), there were 286 (72.4%) deaths including 231 cancer-related deaths. The median time from the first ICI to event was 7.7 months (IQR: 4.0-16.8). PS matching of 56 antibiotic users with 99 nonusers showed that concurrent antibiotic use with ICI was associated with higher cancer-related (aHR: 1.66; 95% CI: 1.08-2.54) and all-cause mortality (aHR: 1.63; 95% CI: 1.17-2.28).Concurrent antibiotic use during immunotherapy was associated with higher mortality in patients with advanced HCC. Further studies should examine the role of gut dysbiosis on responses to ICI.