tbuckley/cabot-search huggingface dataset:
Improving differential diagnosis of pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer via a transcriptomic, biological pathway-based ridge regression model.
Authors: Jun Hong, Likun Hou, Wei Zhang, Zhengwei Dong, Zhan Huang, Wuzhou Yuan, Lei Zhang, Chunyan Wu
Journal: Journal of Clinical Oncology (2021)

3065 Background: In clinics, it can be challenging to make correct diagnosis of LCNEC, Small cell lung cancer (SCLC), if tissues, like needle biopsies, are insufficient or morphology was poorly preserved. In this study, a reliable classifier was constructed based on transcriptome data and machine learning (Ridge regression) to improve the diagnostic accuracy for LCNEC and SCLC. Methods: RNA-Seq data obtained from 3 public cohorts were collected as training set, including 60 NSCLC cases from The Cancer Genome Atlas (TCGA), 66 LCNEC cases from Julie George et al., Nature Communications 2018, and 33 SCLC cases from Julie George et al., Nature 2015. Another 80 NSCLC, 30 LCNEC and 15 SCLC cases published by Martin Peifer et al., Nature Genetics 2012 were used as validation set. Additionally, RNA-Seq data of 27 borderline samples which were hard to make diagnosis based on histology and Immunohistochemistry were used to test the accuracy of the prediction model. Results: 13,959 genes mapped to 186 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were included. Gene Set Variation Analysis (GSVA) algorithm was used to enrich and score each KEGG pathway. A prediction model based on GSVA score of each pathway was constructed via Ridge regression. This GSVA Score Model achieved ROC-AUC 0.949 and concordant rate of 0.75 for the entire prediction efficiency. Of the 27 borderline samples which were hard to make confirmed diagnosis, 17/27 (63.0%) were predicted as LCNEC, 7/27 were predicted as SCLC, and the remainder were predicted as NSCLC. While only 8 (29.6%) cases with LCNEC were diagnosed by pathologists, which was significantly lower than the results predicted by the model. Furthermore, cases with model predicted LCNEC had a significant longer disease-free survival than that with model predicted SCLC (median DFS,59 months for LCNEC vs 5 months for SCLC, p = 0.0043), which was in parallel with currently known prognostic difference of these two types of neuroendocrine tumors. Conclusions: This GSVA algorithm-based prediction model was able to make accurate diagnosis of LCNEC and SCLC. And it may provide valuable information for clinics to choose optimal therapeutic approach for patients with pulmonary neuroendocrine tumors.[Table: see text]
Antibody Response to Sars-Cov-2 Vaccination in Patients Following Allogeneic Hematopoietic Cell Transplantation
Authors: Caroline Cicin-Sain, Alice Huang, Chloe Pasin, Selina Epp, Nicolas J Mueller, Jakob Nilsson, Oliver Vilinovszki, Gayathri Nair, Nathan Wolfensberger, Philipp Hockl, Urs Schanz, Alexandra Trkola, Roger Kouyos, Barbara Hasse, Annelies Zinkernagel, Markus G Manz, Irene A Abela, Antonia MS Mueller
Journal: Blood (2021)
Abstract #4902: CD44, CD29 and CD133 as potential markers for Cancer Stem Cells (CSC) in Head and Neck Squamous Cell Carcinoma (HNSCC)
Authors: Aymee Perez, Lutecia Pereira, David Neskey, W Goodwin, Joyce Slingerland, Elizabeth Franzmann
Journal: Cancer Research (2009)

Introduction: Recent work indicates the there is a small subpopulation of malignant stem cells that are responsible for the initiation, growth, recurrence and metastasis of solid tumors, including squamous cell carcinoma of the head and neck region (HNSCC). Cells with stem cell characteristics have also been identified in cell lines derived from other cancers. The aim of the present work was to characterize stem cell markers in HNSCC cell lines. Methods: The ATCC SCC 9, 15, and 25 established cell lines were examined for their pattern of colony morphologies, expression of the putative stem cell markers CD44, CD133 and CD29 by FACS analysis and their ability to form spheroids in the absence of attachments. To determine the relationship of CD44 expression to cisplatin sensitivity in vitro, two stable CD44 expressing clones were created in the established ATCC SCC25 cell line and were analyzed for cisplatin sensitivity. Results: All HNSCC established cell lines showed a holoclone/meroclone/paraclone series of colony morphologies and formed spheres when cultured in suspension. Re-passaging of primary spheres of all cell lines showed the ability to form secondary spheres with an increase in the total number of spheres. When cells from secondary spheres were dissociated and plated into standard tissue culture plates, they adhered and formed colonies with mainly holoclone morphologies. FACS analysis of the primary \#8216;cancer spheroids\#8217; showed a co-expression of high levels of CD44 and CD29, but only a very small fraction of highly expressing CD133 showed high co-expression of CD44 or CD29. The average IC50 (drug dose to inhibit 50% of cell growth) for the HNSCC cell line with no expression of CD44 was   Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4902.
NLRP3 inflammasome <i>via</i> IL-1β regulates PCSK9 secretion: Erratum
Authors: Zufeng Ding, Xianwei Wang, Shijie Liu, Sichang Zhou, Rajshekhar A Kore, Shengyu Mu, Xiaoyan Deng, Yubo Fan, Jawahar L Mehta
Journal: Theranostics (2021)

[This corrects the article DOI: 10.7150/thno.45939.].
IL‐6–induced cGGNBP2 encodes a protein to promote cell growth and metastasis in intrahepatic cholangiocarcinoma
Authors: Hui Li, Tian Lan, Hailing Liu, Chang Liu, Junlong Dai, Lin Xu, Yunshi Cai, Guimin Hou, Kunlin Xie, Mingheng Liao, Jiaxin Li, Jiwei Huang, Kefei Yuan, Genshu Wang, Yong Zeng, Hong Wu
Journal: Hepatology (2021)

Abstract Background and Aims IL‐6–induced tumor progression has been well established through the induction of antiapoptotic and proliferative genes. However, whether other mechanisms such as IL‐6 regulation of circular RNAs (circRNAs) may also contribute to tumor development remains unknown. Approach and Results High‐throughput RNA sequencing was used to identify the differentially expressed circRNAs on IL‐6 stimulation in intrahepatic cholangiocarcinoma (ICC) cells. CircRNA GGNBP2 (derived from ggnbp2 gene, termed as cGGNBP2) was up‐regulated by IL‐6 treatment in a time and concentration‐dependent manner. The biogenesis of cGGNBP2 was regulated by RNA‐binding protein DEx‐H Box Helicase 9, which was also mediated by IL‐6 exposure. Mass spectrometry and western blotting identified a protein cGGNBP2‐184aa encoded by cGGNBP2. cGGNBP2‐184aa promoted ICC cell proliferation and metastasis in vitro and in vivo. Mechanistically, cGGNBP2‐184aa directly interacted with signal transducers and activators of transduction‐3 (STAT3), phosphorylated STAT3 Tyr705 , and played a positive regulatory role in modulating IL‐6/STAT3 signaling. IL‐6/cGGNBP2‐184aa/STAT3 formed a positive feedback loop to sustain constitutive activation of IL‐6/STAT3 signaling. Elevated cGGNBP2 expression was correlated with poor prognosis of patients with ICC and was identified as an independent risk factor for patient prognosis. Conclusions Our study demonstrates that cGGNBP2‐184aa, a protein encoded by IL‐6–induced cGGNBP2, formed a positive feedback loop to facilitate ICC progression and may serve as an auxiliary target for clinical IL‐6/STAT3‐targeting treatments in ICC.
Sickle Cell Disease in Sweden - Prevalence and Resource Use Estimated through Population-Based National Registers
Authors: Christian Kjellander, Emma Hernlund, Moa Ivergård, Axel Svedbom, Therese Dibbern, Anna Stenling, Fredrik Sjöö, Simona Vertuani, Andreas Glenthøj, Honar Cherif
Journal: Blood (2021)
Effects of Prior Exposure to Tec Kinase(BTK/ITK) Inhibitors on Kte-X19 Products
Authors: Irene Scarfò, Kathleen M.E. Gallagher, Mark B. Leick, Michael C. Kann, Justin Budka, Bharat Sowrirajan, Kim Nguyen, Rhine R. Shen, Adrian Bot, Marcela V. Maus
Journal: Blood (2021)
Phase 1 Study of CD37-Directed CAR T Cells in Patients with Relapsed or Refractory CD37+ Hematologic Malignancies
Authors: Matthew J. Frigault, Yi-Bin Chen, Kathleen M.E. Gallagher, Nora K. Horick, Areej El-Jawahri, Irene Scarfò, Marc Wehrli, Lu Huang, Keagan Casey, Daniella Cook, Thomas Spitzer, Steven McAfee, Frederic I. Preffer, Myriam Armant, Kit L. Shaw, Heather Daley, Sarah Nikiforow, Jerome Ritz, Marcela V. Maus
Journal: Blood (2021)
An Inducible Leukemia-Associated Transcription Factor Facilitates Large-Scale <i>Ex Vivo</i> Generation of Functional Human Macrophages
Authors: Roland Windisch, Sarah Soliman, Adrian Hoffmann, Linping Chen-Wichmann, Sebastian Lutz, Christian Kellner, Enric Redondo Monte, Sebastian Vosberg, Luise Hartmann, Stephanie Schneider, Fabian Beier, Carolin Dorothea Strobl, Oliver Weigert, Matthias Peipp, Michael Schündeln, Jürgen Bernhagen, Andreas Humpe, Christian Brendel, Hannes Klump, Philipp A. Greif, Christian Wichmann
Journal: Blood (2021)
Frequency and Antibiotic Susceptibility of Acinetobacter Baumannii in Surgical site Infections at Rawalpindi Institute of Cardiology
Authors: Arif Maqsood Ali, Agha Babar Hussain, Azhar Mehmood Kayani
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Acinetobacter is an important nosocomial pathogen to cause infections such as pneumonia, bloodstream infections, meningitis, wound and surgical site infections including flesh eating bacterium necrotizing fasciitis and urinary tract Infections. A. baumannii can be spread through direct contact with surfaces, objects and the skin of contaminated persons. Acinetobactter has acquired resistance to most of the antibiotics and can play havoc in hospital environment due to its ability to survive desiccation and in moist environment in the presence of disinfectants. Currently, there are 32 genospecies of Acinetobacter known. Among these, A. baumannii is the most important in the clinical context, since it is the most frequently isolated in nosocomial infections and the one associated with the highest mortality rate. Objective To find out the frequency of A. baumannii causing surgical site infections after cardiac surgery and best antibiotic options for its treatment in patients admitted in Rawalpindi Institute of Cardiology. Materials and Methods A retrospective study was carried out to find out bacterial cultures in admitted patients at Rawalpindi Institute of Cardiology with surgical site infections from July 2017 to August 2018. A total of 405 pus specimens collected from patients with suspected surgical site infections were tested for bacterial culture and antimicrobial susceptibility test. Patient profile was noted from centralized hospital data. Results Out of total 405 specimens 13 were culture positive for A. baumannii (3.2%). Ten isolates were Pan Drug Resistant (PDR). Conclusion A. baumannii infection although infrequent in our set up is mostly pan resistant. Infection control practices &amp; surveillance are important to avoid its spread in hospitalized patients.
Navtemadlin (KRT-232), a Small Molecule MDM2 Inhibitor, Is More Effective Than Decitabine Against Myeloproliferative Neoplasm-Blast Phase in a Patient-Derived Xenograft Model
Authors: Xiaoli Wang, Cing Siang Hu, Virginia Gillespie, Cecile Marie Krejsa, Ronald Hoffman
Journal: Blood (2021)
Daratumumab, Cyclophosphamide, Bortezomib, Lenalidomide, Dexamethasone (Dara-CVRd), V-Augmented Autologous Stem Cell Transplant (V-ASCT) and Dara-Vrd Consolidation in Ultra-High Risk (UHiR) Newly Diagnosed Myeloma (NDMM) and Primary Plasma Cell Leukemia (pPCL) Compared with Myeloma XI/XI+ Trial Treatment for Uhir MM: The UK Optimum/Muknine Trial
Authors: Martin F. Kaiser, Andrew Hall, Katrina Walker, Nicola Newnham, Ruth M. de Tute, Sadie Roberts, Emma Ingleson, Kristian M Bowles, Mamta Garg, Anand Lokare, Christina Messiou, Graham Jackson, Gordon Cook, Guy Pratt, Roger G Owen, Mark T Drayson, Sarah R Brown, Matthew W Jenner
Journal: Blood (2021)
Myelodysplastic Syndromes: A More Global 5-Hydroxymethylcytosine Deficiency Disorder Than Suggested By the Presence of TET2 Mutations
Authors: Carmelo Gurnari, Simona Pagliuca, Yihong Guan, Courtney E. Hershberger, Ying Ni, Jaymeson Gordon, Hetty E. Carraway, Richard A Padgett, Diego Coutinho, Ilana Zalcberg, Jae-Sook Ahn, Hyeoung-Joon Kim, Dennis Dong Hwan Kim, Mark D. Minden, Joop H. Jansen, Babal K. Jha, Torsten Haferlach, Jaroslaw P. Maciejewski, Valeria Visconte
Journal: Blood (2021)
The anti-inflammatory effect of bacterial short chain fatty acids is partially mediated by endocannabinoids
Authors: Amrita Vijay, Afroditi Kouraki, Sameer Gohir, James Turnbull, Anthony Kelly, Vicky Chapman, David A Barrett, William J Bulsiewicz, Ana M Valdes
Journal: Gut Microbes (2021)

The endocannabinoid (EC) system has pleiotropic functions in the body. It plays a key role in energy homeostasis and the development of metabolic disorders being a mediator in the relationship between the gut microbiota and host metabolism. In the current study we explore the functional interactions between the endocannabinoid system and the gut microbiome in modulating inflammatory markers. Using data from a 6 week exercise intervention (treatment n = 38 control n = 40) and a cross sectional validation cohort (n = 35), we measured the associations of 2-arachidonoylglycerol (2-AG), anandamide (AEA), N-oleoylethanolamine (OEA) and N-palmitoylethanolamine (PEA) with gut microbiome composition, gut derived metabolites (SCFAs) and inflammatory markers both cross-sectionally and longitudinally. At baseline AEA and OEA were positively associated with alpha diversity (β(SE) = .32 (.06), P = .002; .44 (.04), P < .001) and with SCFA producing bacteria such as Bifidobacterium (2-AG β(SE) = .21 (.10), P < .01; PEA β(SE) = .23 (.08), P < .01), Coprococcus 3 and Faecalibacterium (PEA β(SE) = .29 (.11), P = .01; .25 (.09), P < .01) and negatively associated with Collinsella (AEA β(SE) = −.31 (.12), P = .004). Additionally, we found AEA to be positively associated with SCFA Butyrate (β(SE) = .34 (.15), P = .01). AEA, OEA and PEA all increased significantly with the exercise intervention but remained constant in the control group. Changes in AEA correlated with SCFA butyrate and increases in AEA and PEA correlated with decreases in TNF-ɑ and IL-6 statistically mediating one third of the effect of SCFAs on these cytokines. Our data show that the anti-inflammatory effects of SCFAs are partly mediated by the EC system suggesting that there may be other pathways involved in the modulation of the immune system via the gut microbiome.
Covid-19: Booster vaccine gives “significant increased protection” in over 50s
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: Booster vaccine gives "significant increased protection" in over 50s Elisabeth MahaseA third Pfizer BioNTech covid-19 vaccine dose-known as a booster dose-provides "significant increased protection" against symptomatic disease in those aged 50 and over, irrespective of which vaccine they initially received. 12
Abstract 8915: Unsupervised Machine Learning Clustering Identifies Low Flow-Low Gradient as High Mortality Risk Phenotypes in Transcatheter Aortic Valve Replacement Patients
Authors: Chiehju Chao, Han-Lun Wu, Pradyumna Agasthi, Corbin Rayfield, Timothy Barry, Olubadewa Fatunde, Amith Seri, Mackram F Eleid, Floyd D Fortuin, John Sweeney, Peter Pollak, Abdallah El Sabbagh, Steven Lester, David R Holmes, Win K Shen, Bhavik Patel, Reza Arsanjani
Journal: Circulation (2021)

Introduction: Multiple supervised machine learning (ML) models have been used to assess the outcomes in patients who underwent transcatheter aortic valve replacement (TAVR) procedure, however, supervised ML requires significant expert time for annotation and labeling. Unsupervised ML can provide insight into the dataset without this process. Hypothesis: We hypothesized that unsupervised k-means ML can identify distinct phenogroups in TAVR patients that can predict prognosis without a priori knowledge. Methods: A retrospective study of patients who underwent TAVR (Jan 2012-Dec 2017) at Mayo Clinic sites was performed. Baseline demographics, EKG, cardiac computed tomography, and echocardiographic data were abstracted. Variables with ≥ 20% missing data were excluded. Prior to the k-means clustering algorithm, principal component analysis was used for dimensionality reduction. Input variables were analyzed according to k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster. Results: A total of 1071 consecutive patients were included in the final analysis. A total of 141 unique variables were used. The mean age was 80.7±8.6 years, 58.2% were male. Patients were divided into 2 distinct phenogroups. In the two phenogroups, cluster 0 (n=639) has significantly better survival than cluster 1 (n= 432) (log-rank p=0.0002) (Figure 1). Cluster 1 has features of low flow-low gradient (LFLG) hemodynamic profile, including lower systolic blood pressure, mean aortic valve gradient, peak aortic valve velocity, and worse LV ejection fraction. Conclusions: Unsupervised ML can identify distinct phenotype features with prognostic significance in TAVR patients. Our results suggest that patients with LFLG hemodynamic features are intrinsically different from other TAVR patients and require more attention to avoid adverse outcomes.
Efficacy, Toxicity and Cost of Venetoclax-Based Combinations for the Treatment of Acute Myeloid Leukemia: Real-World Evidence from a Canadian Academic Center
Authors: Philippe Bouchard, Annie Brisebois-Boyer, Anne Beaudry, Jean-Francois Berthiaume, Nadia M. Bambace, Léa Bernard, Josee Hebert, Julie Bergeron
Journal: Blood (2021)
Drawing Boundaries around PARADISE
Authors: Lynne W. Stevenson, Andrew P. DeFilippis
Journal: New England Journal of Medicine (2021)

Fight-or-flight systems evolved to support humans through acute physiological threats that are now less common than chronic cardiovascular stress. Progressive activation of the sympathetic nervous system and the renin–angiotensin–aldosterone system (RAAS) contributes to chronic heart failure, including that which occurs after acute myocardial infarction. Pharmacologic inhibition of the RAAS improves cardiac structure, function, and outcomes. In addition, the natriuretic peptide system is now recognized to provide counterbalance to the RAAS, enhancing natriuresis and vasodilation while decreasing fibrosis and apoptosis. Neprilysin, a zinc-dependent neutral endopeptidase, degrades more than 20 peptides, including natriuretic peptides, angiotensin II, endothelin-1, and bradykinin, and is inhibited . . .
Treatment-free survival over extended follow-up of patients with advanced melanoma treated with immune checkpoint inhibitors in CheckMate 067
Authors: Meredith M Regan, Charlene M Mantia, Lillian Werner, Ahmad A Tarhini, James Larkin, F Stephen Hodi, Jedd Wolchok, Michael A Postow, Brian Stwalley, Andriy Moshyk, Corey Ritchings, Sandra Re, Wim van Dijck, David F McDermott, Michael B Atkins
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Treatment-free survival (TFS) characterizes disease control after discontinuation of immune checkpoint inhibitors (ICIs) until subsequent therapy or death. We previously evaluated TFS in a pooled analysis of the CheckMate 067 and CheckMate 069 trials of the ICIs nivolumab and ipilimumab, alone or in combination, in patients with advanced melanoma after minimum follow-up of 36 months. This analysis investigated TFS differences between treatments in CheckMate 067 after a minimum follow-up of 60 months, and their relation to overall survival (OS) differences. Methods Data were from 937 patients who initiated treatment (nivolumab plus ipilimumab, nivolumab, or ipilimumab) in CheckMate 067 ( NCT01844505 ). TFS was defined as the area between the Kaplan-Meier curves for time to protocol therapy cessation and time to subsequent systemic therapy initiation or death, each measured from randomization. TFS was partitioned as time with and without toxicity. Toxicity included persistent and late-onset grade ≥2 select treatment-related adverse events (ie, those of potential immunologic etiology). The area between Kaplan-Meier curves was estimated by the difference in 60-month restricted-mean times of the endpoints. Between-group differences were estimated with bootstrapped 95% CIs. Results At 60 months from randomization, 39%, 24%, and 11% of patients assigned to treatment with nivolumab plus ipilimumab, nivolumab, and ipilimumab, respectively, had survived and were treatment-free. The 60-month mean TFS was approximately twice as long with the combination (19.7 months) than with nivolumab (9.9 months; absolute difference, 9.8 (95% CI 6.7 to 12.8)) or ipilimumab (11.9 months; absolute difference, 7.8 (95% CI 4.6 to 11.0)). In the respective groups, mean TFS represented 33% (8% with and 25% without toxicity), 17% (2% and 14%), and 20% (3% and 17%) of the 60-month period. Compared with 36-month estimates, mean TFS over the 60-month period represented slightly greater percentages of time in the nivolumab-containing regimen groups and a lesser percentage in the ipilimumab group. TFS differences between the combination and either monotherapy increased with longer follow-up. Conclusions Along with improved long-term OS with the nivolumab-containing regimens versus ipilimumab, TFS without toxicity was sustained with nivolumab plus ipilimumab versus either monotherapy, demonstrating larger between-group differences with extended follow-up.
"My T Cell": A Smartphone Application for Guidance of CAR T Logistics and Management of CAR T &amp; BiTE Related Toxicities
Authors: Viktoria Blumenberg, Lisa Siegmund, Lisa Frölich, Kai Rejeski, Friederike Hildebrandt, Christian Schmidt, Michael von Bergwelt, Veit L Buecklein, Marion Subklewe
Journal: Blood (2021)
The long-circulating effect of pegylated nanoparticles revisited via simultaneous monitoring of both the drug payloads and nanocarriers
Authors: Wufa Fan, Haixia Peng, Zhou Yu, Luting Wang, Haisheng He, Yuhua Ma, Jianping Qi, Yi Lu, Wei Wu
Journal: Acta Pharmaceutica Sinica B (2021)

The long-circulating effect is revisited by simultaneous monitoring of the drug payloads and nanocarriers following intravenous administration of doxorubicin (DOX)-loaded methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) nanoparticles. Comparison of the kinetic profiles of both DOX and nanocarriers verifies the long-circulating effect, though of limited degree, as a result of pegylation. The nanocarrier profiles display fast clearance from the blood despite dense PEG decoration; DOX is cleared faster than the nanocarriers. The nanocarriers circulate longer than DOX in the blood, suggesting possible leakage of DOX from the nanocarriers. Hepatic accumulation is the highest among all organs and tissues investigated, which however is reversely proportionate to blood circulation time. Pegylation and reduction in particle size prove to extend circulation of drug nanocarriers in the blood with simultaneous decrease in uptake by various organs of the mononuclear phagocytic system. It is concluded that the long-circulating effect of mPEG-PCL nanoparticles is reconfirmed by monitoring of either DOX or the nanocarriers, but the faster clearance of DOX suggests possible leakage of a fraction of the payloads. The findings of this study are of potential translational significance in design of nanocarriers towards optimization of both therapeutic and toxic effects.