tbuckley/cabot-search huggingface dataset:
Abstract 9048: Heart Failure Training Course for Home Health Aides in New York City: A Mixed Methods Pilot Study
Authors: Madeline R Sterling, Jacklyn Cho, Peggy Leung, joanna Ringel, Ariel Silva, Anthony Poon, Oscar Toro, Natasha Herring, Alena K Powell, Parag Goyal, Loughman Julia, Michael Obodai, Monika M Safford
Journal: Circulation (2021)

Introduction: Although home health aides (HHAs) often care for adults with heart failure (HF), studies have found that the majority have not received HF training and lack confidence with HF caregiving. To address this, we tested the feasibility, acceptability, and effectiveness of a virtual HF training course for HHAs. Methods: We partnered with the Education Fund of the 1199SEIU United Health Care Workers East, the largest healthcare union in the US, which provides training to 55,000 HHAs in NYC. HHAs typically receive in-person training, but due to COVID-19, we conducted this course virtually. The 2-hour course, taught in English and Spanish, utilized case-based learning and motivational interviewing to engage HHAs in interactive discussions on HF signs, symptoms, and HF self-care. HHAs with access to Zoom (via smartphone, computer, or tablet) were eligible. We conducted pre/post surveys and semi-structured interviews. Measures included: a) feasibility (attendance, retention), b) acceptability (modality, technological ease, satisfaction); and c) effectiveness (change in knowledge [Dutch Heart Failure Knowledge Scale, range 0-15] and caregiving self-efficacy [HF Caregiver Self-efficacy Scale, range 0-100]). Results: 48 HHAs employed by 15 distinct home care agencies enrolled and completed the course; course size ranged from 4-9 participants. The majority were middle-age women (60% Hispanic, 10% non-Hispanic Black). To participate, 59% used a smartphone, 32% a computer, and 10% a tablet. Compared to prior in-person courses, 83% participants reported that the course ran more smoothly and was more convenient; only 7% reported technical problems. Participants and course instructors reported high levels of satisfaction and engagement. Post-course data showed significant and clinically meaningful improvements in HF knowledge (11.21 [1.90] v. 12.21 [1.85]; p = 0.0000) and HF caregiving self-efficacy (75.21 [16.57] v. 82.29 [16.49]; p = 0.0017). Conclusions: A virtual HF training course was feasible and acceptable among HHAs and improved their HF knowledge and caregiving confidence. Efforts to scale and disseminate the course may be warranted. Future studies are needed to test the effect of the course among HHAs and their patients.
Rivaroxaban or Placebo for Extended Antithrombotic Prophylaxis after Laparoscopic Surgery for Colorectal Cancer. the PRO-LAPS II Study
Authors: Cecilia Becattini, Ugo Pace, Felice Pirozzi, Giampiero Avruscio, Annibale Donini, Fabio Rondelli, Adriana Visonà, Michela Boncompagni, Marco De Prizio, Damiano Chiari, Andrea Muratore, Francesco Guerra, Raffaele De Luca, Giuseppe Portale, Marco Milone, Marc Righini, Giampaolo Castagnoli, Roberto Persiani, Jacopo Martellucci, Stefania Frasson, Francesco Dentali, Paolo Delrio, Antonio Sciuto, Gualberto Gussoni, Giancarlo Agnelli
Journal: Blood (2021)
Avenue - Avelumab in the Frontline Treatment of Advanced Classic Hodgkin Lymphoma - a Window Study
Authors: Stephen Booth, Eliza Hawkes, Amy A Kirkwood, Sally F Barrington, Patrick G. Medd, Pamela McKay, Ruth Pettengell, Sunil Iyengar, Fiona Miall, John Radford, Cathy Burton, Amit Sud, Nimish Shah, Andrew M Scott, Arzhang Ardavan, Michael Northend, Laura Clifton-Hadley, Richard Jenner, Graham P. Collins
Journal: Blood (2021)
SEA-BCMA, an Investigational Nonfucosylated Monoclonal Antibody: Ongoing Results of a Phase 1 Study in Patients with Relapsed/Refractory Multiple Myeloma (SGNBCMA-001)
Authors: James E Hoffman, Brea Lipe, Jason Melear, Michaela Liedtke, Mark A. Schroeder, Ruben Niesvizky, Michael H. Tomasson, Christopher A. Yasenchak, Damian J. Green, Hong Li, Yinghui Wang, Phoenix Ho, Al-Ola Abdallah
Journal: Blood (2021)
Disparities in COVID-19 Outcomes by Race, Ethnicity, and Socioeconomic Status
Authors: Shruti Magesh, Daniel John, Wei Tse Li, Yuxiang Li, Aidan Mattingly-app, Sharad Jain, Eric Y. Chang, Weg M. Ongkeko
Journal: JAMA Network Open (2021)

COVID-19 has disproportionately affected racial and ethnic minority groups, and race and ethnicity have been associated with disease severity. However, the association of socioeconomic determinants with racial disparities in COVID-19 outcomes remains unclear.To evaluate the association of race and ethnicity with COVID-19 outcomes and to examine the association between race, ethnicity, COVID-19 outcomes, and socioeconomic determinants.A systematic search of PubMed, medRxiv, bioRxiv, Embase, and the World Health Organization COVID-19 databases was performed for studies published from January 1, 2020, to January 6, 2021.Studies that reported data on associations between race and ethnicity and COVID-19 positivity, disease severity, and socioeconomic status were included and screened by 2 independent reviewers. Studies that did not have a satisfactory quality score were excluded. Overall, less than 1% (0.47%) of initially identified studies met selection criteria.Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Associations were assessed using adjusted and unadjusted risk ratios (RRs) and odds ratios (ORs), combined prevalence, and metaregression. Data were pooled using a random-effects model.The main measures were RRs, ORs, and combined prevalence values.A total of 4 318 929 patients from 68 studies were included in this meta-analysis. Overall, 370 933 patients (8.6%) were African American, 9082 (0.2%) were American Indian or Alaska Native, 101 793 (2.4%) were Asian American, 851 392 identified as Hispanic/Latino (19.7%), 7417 (0.2%) were Pacific Islander, 1 037 996 (24.0%) were White, and 269 040 (6.2%) identified as multiracial and another race or ethnicity. In age- and sex-adjusted analyses, African American individuals (RR, 3.54; 95% CI, 1.38-9.07; P = .008) and Hispanic individuals (RR, 4.68; 95% CI, 1.28-17.20; P = .02) were the most likely to test positive for COVID-19. Asian American individuals had the highest risk of intensive care unit admission (RR, 1.93; 95% CI, 1.60-2.34, P < .001). The area deprivation index was positively correlated with mortality rates in Asian American and Hispanic individuals (P < .001). Decreased access to clinical care was positively correlated with COVID-19 positivity in Hispanic individuals (P < .001) and African American individuals (P < .001).In this study, members of racial and ethnic minority groups had higher risks of COVID-19 positivity and disease severity. Furthermore, socioeconomic determinants were strongly associated with COVID-19 outcomes in racial and ethnic minority populations.
47 Tertiary lymphoid structures (TLS) in desmoplastic melanomas (DM) differ from non-DM-associated TLS by their intratumoral location and enhanced immune activity
Authors: Ileana Mauldin, Anne Stowman, Alexandra Hickman, Adela Mahmutovic, Alejandro Gru, Kevin Lynch, Samuel Young, Max Meneveau, Nolan Wages, Victor Engelhard, Craig Slingluff
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Tertiary lymphoid structures (TLS) are ectopic lymphoid organs that are localized near tumors and other sites of inflammation, and are commonly believed to support antitumor immunity. We previously published studies that show that most desmoplastic melanomas contain TLS, and that TLS in cutaneous metastatic melanomas varied widely in maturation state, in proportions of proliferating T and B cells, and in markers of B cell function, including AID and CD21. Thus, we hypothesized that there may be diversity in TLS function, or immunologic activity, among melanomas. To address this hypothesis, we evaluated TLS in primary desmoplastic melanomas (DM), and non-desmoplastic melanomas (non-DM) for markers of cell proliferation which are indicative of early immune activity. Methods DM and non-DM tumor specimens, which included primary melanomas (PM), and cutaneous metastatic melanomas (CMM), were evaluated for TLS by multiplex Immunofluorescence histology, by staining for CD20, CD8, PNAd, Ki67, FoxP3, and DAPI. Lymphoid aggregates were identified in 20x spectrally unmixed images by visual inspection and identified as TLS if possessing organized T-cell and B-cell regions in addition to high endothelial venule-like vasculature (PNAd+). TLS were identified in 30 out of 64 screened (48%) CMM, 4/4 non-DM PM, and 8 out of 11 screened (73%) DM. Immune cells localized in TLS were enumerated using Halo software (Indica Labs). Mann-Whitney tests were used for statistical assessments. Results DM commonly contain a dense network of fibroblasts and associated stroma, which are not typical for other non-DM (PM and CMM). TLS in DM are located throughout the tumors, intratumorally, in sharp distinction from the peritumoral location of TLS in non-DM. Furthermore, when compared to TLS of non-DM (PM and CMM), TLS of DM contain increased densities of CD20+ B cells (PM p=0.007; CMM p&lt;0.0001) and CD8+ T cells (PM p=0.017; CMM p=0.0006), and a higher proportion of proliferating (Ki67+) CD20+ B cells (PM p=0.04; CMM p=0.009). Conclusions Recently published studies have identified tumor-associated fibroblasts as the likely initiating cells for TLS formation in murine melanomas. The intratumoral location of TLS in DM puts them in close proximity to the dense fibroblasts and desmoplastic stroma in these tumors, which may be responsible for their intratumoral location. The increased density of B and T cells, and higher proportion of proliferating (Ki67+) B cells, in DM than in non-DM, suggests that there may be greater immune activation, increased germinal center maturation, or less regulation in TLS of DM. Ethics Approval Approval was obtained for these studies under IRB protocol #’s 10598 and 19694.
Phase 1 Results of Novel Combination Therapy: BET Inhibitor PLX51107 with Azacitidine in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Authors: Naveen Pemmaraju, Kapil N. Bhalla, Naval Daver, Nathaniel R Wilson, Warren C. Fiskus, Farhad Ravandi, Guillermo Garcia-Manero, Tapan M. Kadia, Courtney D. DiNardo, Elias J. Jabbour, Jan A. Burger, Nicholas J. Short, Yesid Alvarado, Nitin Jain, Lucia Masarova, Srdan Verstovsek, Ghayas C. Issa, Wei Qiao, Joseph D. Khoury, Sherry A. Pierce, Darla Miller, Marina Konopleva, Hagop Kantarjian, Gautam Borthakur
Journal: Blood (2021)
Abstract PO-049: Inhibiting MNK kinases promotes macrophage immunosuppressive phenotype to limit anti-tumor immunity
Authors: Thao N. D. Pham, Christina Spaulding, Mario A. Shields, Mahmoud G. Khalafalla, Daniel R. Principe, David J. Bentrem, Hidayatullah G. Munshi
Journal: Cancer Research (2021)

Abstract Background MAPK-interacting serine/threonine-protein kinase 1 and 2 (MNK1 and MNK2) are downstream effectors of the MEK/ERK and p38 MAPK pathways. Increased expression and activity of MNK kinases are linked to tumor growth and therapeutic resistance. Select MNK kinase inhibitors are currently being evaluated in clinical trials for different tumor types. Their immunomodulatory effects in tumors with low infiltrating CD8+ T have not been clearly defined. Methods: In vivo efficacy of MNK kinase inhibitors (CGP57380 and eFT508), either as a single agent or in combination with anti-PD-1 or anti-CSF-1R antibody, was tested in syngeneic mouse models of pancreatic cancer. Tumor-associated macrophages (TAMs) and murine bone marrow-derived macrophages (BMDMs) were evaluated in vitro for modulation of their polarization by MNK kinase inhibitors and their suppression of co-cultured T cells. Markers of M1/M2 polarization were measured by qRT-PCR. The effects of MNK kinase inhibitors on the expression of select M2 markers were also evaluated in ex vivo slice cultures of human pancreatic tumors. Results: We first found an inverse relationship between MNK kinase activity and CD8+ T cell abundance in human pancreatic tumors. In tumor-bearing mice, while pharmacological inhibition of MNK kinase activity increased CD8+ T cell infiltration, the tumor-infiltrating CD8+ T cells lacked effector function and failed to mount anti-tumor responses. Mechanistically, we showed that systemic inhibition of MNK kinases increased the expression of several anti-inflammatory genes in BMDMs and potentiated the ability of BMDMs and TAMs to suppress T cell proliferation. Reversal of T cell exhaustion either by an anti-PD-1 antibody or by TAM depletion with an anti-CSF-1R antibody enhanced the anti-tumor efficacy of MNK inhibitors and prolonged animal survival. Importantly, treating ex vivo human pancreatic cancer slice cultures with MNK inhibitors led to increased expression of known immunosuppressive markers in TAMs. Conclusion: Together, these findings provide new insights into the effects of MNK kinase inhibition on CD8+ T cell infiltration and TAM function and identify combination regimens with MNK kinase inhibitors to achieve effective anti-tumor responses in pancreatic cancer patients whose tumors have a low number of functional CD8+ T cells. Citation Format: Thao N. D. Pham, Christina Spaulding, Mario A. Shields, Mahmoud G. Khalafalla, Daniel R. Principe, David J. Bentrem, Hidayatullah G. Munshi. Inhibiting MNK kinases promotes macrophage immunosuppressive phenotype to limit anti-tumor immunity [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-049.
Abstract 9373: Cinnamamide Derivative Reduces Left Ventricular Dysfunction by Modulating Mitochondrial Dynamics in Prediabetic Rats
Authors: Natticha Sumneang, Thura Tun T Oo, Busarin Arunsak, Wasana Pratchayasakul, Nattayaporn Apaijai, Guang Liang, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Circulation (2021)

Introduction: Chronic high-fat diet (HFD) consumption induces prediabetes via increased systemic inflammation by activating myeloid differentiation factor 2 (MD2)/toll-like receptor 4 pathway, resulting in left ventricular (LV) dysfunction. Cinnamamide derivative was shown previously to reduce inflammation in lipopolysaccharide-induced septic mice by targeting MD2. However, the effects of cinnamamide derivative, 2i-10, on the LV function in prediabetes are not known. Hypothesis: 2i-10 improves LV function in prediabetic rats by reducing cardiac inflammation, mitochondrial dysfunction, and mitochondrial dynamics imbalance. Methods: Prediabetic rats were induced by feeding HFD for 12 weeks, and were divided into 3 groups; vehicle, 2i-10 (40 mg/kg), or metformin (300 mg/kg). Normal diet fed rats received vehicle. Rats orally received their assigned treatment for 4 weeks. Then, LV function, cardiac inflammation, and mitochondrial function and dynamics were examined. Results: Prediabetic rats had impaired LV function, as shown by reduced %LV ejection fraction. Moreover, impaired mitochondrial function and dynamics were observed, as shown by increased reactive oxygen species (ROS), mitochondrial depolarization, swelling, increased mitochondrial fission (p-Drp1/Drp1) and decreased mitochondrial fusion (OPA1). NF-κB phosphorylation was increased in these rats, indicating inflammation. Treatment with 2i-10 significantly reduced cardiac inflammation, mitochondrial dysfunction, mitochondrial dynamic imbalance, and improved LV function in prediabetic rats (Fig 1). Similar benefits were observed in metformin-treated rats. Conclusions: Chronic treatment with 2i-10, effectively suppressed cardiac inflammation, mitochondrial dysfunction and mitochondrial dynamics imbalance, leading to improved LV function in prediabetic rats. These findings suggest that targeting MD2 could be a novel treatment to protect the heart in prediabetes.
Common pathways in dementia and diabetic retinopathy: understanding the mechanisms of diabetes-related cognitive decline
Authors: Karis Little, María Llorián-Salvador, Sarah Scullion, Cristina Hernández, Olga Simó-Servat, Angel del Marco, Esmeralda Bosma, Maria Vargas-Soria, Maria Jose Carranza-Naval, Tine Van Bergen, Silvia Galbiati, Ilaria Viganò, Clara Alice Musi, Reiner Schlingemann, Jean Feyen, Tiziana Borsello, Gianpaolo Zerbini, Ingeborg Klaassen, Monica Garcia-Alloza, Rafael Simó, Alan W. Stitt
Journal: Trends in Endocrinology and Metabolism (2021)
Abstract 9825: Stenotic Pulmonary Artery Reconstruction Using in vivo Tissue Engineered Vascular Grafts
Authors: Yoshinobu Maeda, Masaaki Yamagishi, Satoshi Asada, Hisayuki Hongu, Eijiro Yamashita, Hiroki Nakatsuji, Takashi Nagase, Rie Nakai, Keiichi Kanda, Tomoya Inoue, Masashi Yamanami, Hitoshi Yaku
Journal: Circulation (2021)

Introduction: We have applied in vivo tissue engineered vascular grafts (TEVGs) created in the patient's body for surgical reconstruction of the pulmonary artery (PA) as a substitute material for a...
40 Precise spatial multiplexing for immune profiling in non-small cell lung cancer FFPE samples with ChipCytometry
Authors: Thomas Campbell, Arne Christians, Adam Northcutt, Crystal Winkeler, Kevin Gamber
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Emergent data indicate that highly multiplexed spatial biomarker analysis has the potential to advance precision medicine in immuno-oncology and inform the discovery of novel biomarkers. Methods Here we present the analysis of clinical FFPE samples from non-small cell lung cancer patients using ChipCytometry, a novel precise spatial multiplexing technology which combines iterative immuno-fluorescent staining with high-dynamic range imaging to facilitate quantitative phenotyping with single-cell resolution. Standard FCS files are generated from multichannel OME-TIFF images, enabling identification of cellular phenotypes via flow cytometry-like hierarchical gating. In this study, a 27-plex assay was used to identify and quantify more than 30 cellular phenotypes and subtypes in FFPE samples. Results The results show precise expression levels for each marker in the assay in each individual cell in the sample, maintaining spatial information about each cell. Spatial analysis of the samples reveals quantifiable heterogeneity of immune cell infiltration within the tumor samples, demonstrating the utility of the ChipCytometry platform for the in-depth immune profiling in clinical samples. Conclusions N/A
Abstract 10122: 'Young' Stroke Related Mortality in the United States: A 'Wake-Up' Call
Authors: Abdul Minhas, Ahmed H Qavi, Safi U Khan, Sourbha Dani, Sachin S Goel, Erin Michos, Stephen J Greene, Marat Fudim
Journal: Circulation (2021)

Introduction: Important disparities in stroke outcomes persist based on sex, race, and ethnicity. The aim of this study was to examine trends in stroke (ischemic and hemorrhagic) related deaths among young adults in the United States from 1999 to 2019 by sex and race/ethnicity. Methods: We used CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) to access National Vital Statistics System data from 1999 to 2019. Stroke related deaths among individuals age 15- 44 years were identified from multiple causes of death and were represented as age-adjusted mortality rates (AAMR) per 100,000 population. Joinpoint regression was used to examine changes in trend and annual percentage change (APC) overall and stratified by sex and race/ethnicity. Results: AAMR was higher in men (3.3) than women (2.8). AAMR was highest in non-Hispanic Black (NHB) (6.6) followed by non-Hispanic American Indian or Alaska Native (NH-AIAN) (4.36), Hispanic (2.65), non-Hispanic White (NHW) (2.45) and lastly non-Hispanic Asian or Pacific Islander (NH-API) (2.24) ethnic groups. AAMR was highest in NHB males (7.07). AAMR related to stroke decreased from 3.7 in 1999 to 2.69 in 2011 and then increased to 2.87 in 2019 (APC 1.0[95% CI, 0.4 to 1.5]). After initial decline, AAMR increased in men (APC 1.2) since 2011, and women (APC 1.8) since 2013 (Figure, Panel A). AAMR increased among NHW (APC 2.4) persons since 2013 and Hispanic (APC 1.5) persons since 2011 (Figure, Panel B). AAMR decreased in NHB (APC -3.9) persons from 1999-2012, and remained stable thereafter. AAMR decreased in NH-API (APC -0.9) persons and did not change significantly in NH-AIAN persons during the entire study period. Conclusion: After initial decline, stroke-related mortality among young adults has increased over the past decade. Stratification by sex and racial/ethnic status reveals significant disparities. Further research is needed to understand and mitigate the factors driving these trends.
Dysregulation of RalA signaling through dual regulatory mechanisms exerts its oncogenic functions in hepatocellular carcinoma
Authors: Lu Tian, Luqing Zhao, Karen Man‐Fong Sze, Charles Shing Kam, Vanessa Sheung‐In Ming, Xia Wang, Vanilla Xin Zhang, Daniel Wai‐Hung Ho, Tan‐To Cheung, Lo‐Kong Chan, Irene Oi‐Lin Ng
Journal: Hepatology (2021)

Abstract Background and Aims Ras‐like (Ral) small guanosine triphosphatases (GTPases), RalA and RalB , are proto‐oncogenes directly downstream of Ras and cycle between the active guanosine triphosphate‐bound and inactive guanosine diphosphate‐bound forms. RalGTPase‐activating protein (RalGAP) complex exerts a negative regulation. Currently, the role of Ral up‐regulation in cancers remains unclear. We aimed to examine the clinical significance, functional implications, and underlying mechanisms of RalA signaling in HCC. Approach and Results Our in‐house and The Cancer Genome Atlas RNA sequencing data and quantitative PCR data revealed significant up‐regulation of RalA in patients’ HCCs. Up‐regulation of RalA was associated with more aggressive tumor behavior and poorer prognosis. Consistently, knockdown of RalA in HCC cells attenuated cell proliferation and migration in vitro and tumorigenicity and metastasis in vivo. We found that RalA up‐regulation was driven by copy number gain and uncovered that SP1 and ETS proto‐oncogene 2 transcription factor cotranscriptionally drove RalA expression. On the other hand, RalGAPA2 knockdown increased the RalA activity and promoted intrahepatic and extrahepatic metastasis in vivo. Consistently, we observed significant RalGAPA2 down‐regulation in patients’ HCCs. Intriguingly, HCC tumors showing simultaneous down‐regulation of RalGAPA2 and up‐regulation of RalA displayed a significant association with more aggressive tumor behavior in terms of more frequent venous invasion, more advanced tumor stage, and poorer overall survival. Of note, Ral inhibition by a Ral‐specific inhibitor RBC8 suppressed the oncogenic functions in a dose‐dependent manner and sensitized HCC cells to sorafenib treatment, with an underlying enhanced inhibition of mammalian target of rapamycin signaling. Conclusions Our results provide biological insight that dysregulation of RalA signaling through dual regulatory mechanisms supports its oncogenic functions in HCC. Targeting RalA may serve as a potential alternative therapeutic approach alone or in combination with currently available therapy.