tbuckley/cabot-search huggingface dataset:
Low CD19 Antigen Density Diminishes Efficacy of CD19 CAR T Cells and Can be Overcome By Rational Redesign of CAR Signaling Domains
Authors: Robbie G. Majzner, Skyler P. Rietberg, Louai Labanieh, Elena Sotillo, Evan W. Weber, Rachel C. Lynn, Johanna L. Theruvath, Constance M. Yuan, Peng Xu, Sang M. Nguyen, Nirali N. Shah, Maryalice Stetler-Stevenson, Terry J. Fry, Daniel W. Lee, Crystal L. Mackall
Journal: Blood (2018)
Invasion by comedo type ductal carcinoma in situ (DCIS) and the expression of CXCL7 and VEGF-D
Authors: Zhuo Tang, Minghuan Yu, Mary Kosir
Journal: Cancer Research (2007)

547  Introduction: Extracellular heparanase activity in malignant breast cancer is important for angiogenesis, invasion and metastasis. However, breast ductal carcinoma in situ (DCIS) presents clinical challenges with evidence of invasion found in at least 20-30% of cases. The purpose of this study is to determine expression of heparanases, VEGF-D, and invasion in DCIS cells compared to malignant breast cancer cells.  Experimental procedures: Using variant cell lines producing xenografts of comedo carcinoma in situ (MCF10DCIS.com) and rapidly growing invasive and metastatic ductal carcinoma (MCF10CA1.cl1), cell invasion assays were performed in BioCoat Matrigel invasion chambers. The gene (VEGF-D and VEGF-C) expression determined by RT-PCR and Western blot was normalized to beta-actin and expressed as a fold difference between the cell lines. Expression of the heparanases HPSE-1 and CXCL7 were determined by Western blot and RT-PCR.  Data: Using invasion at 24 and 48 hours, malignant MCF10CA1.cl1 invasion was 61.4% compared with 23.8% by MCF10DCIS.com. VEGF-C protein and m-RNA expression were the same for both cell lines, but VEGF-D expression was 30% higher in MCF10DCIS.com than in MCF10CA1.cl1. HPSE-1 mRNA and protein expression was similar in both cell lines, but CXCL7 mRNA expression was significantly higher in MCF10DCIS.com cells than MCF10CA1.cl1 or premalignant cells (p  Conclusions: The comedo type DCIS cells express more CXCL7 mRNA and VEGF-D protein and mRNA than malignant MCF10CA1.cl1 cells. Though less invasive by standard assays than the malignant variant, the comedo MCF10DCIS.com cells are still five times more invasive than premalignant isogenic cells. The ability to invade through basement membrane by comedo DCIS cells may be associated with CXCL7 expression and VEGF-D expression.  #
Lifestyle medicine: we must keep informed to best serve our patients
Authors: Miriam Maisel
Journal: BMJ (2018)

I was one of the first cohort of doctors to sit the lifestyle medicine examination in Edinburgh earlier this year, after years of study and practice.1 Although lifestyle and nutrition is listed as the initial step in guideline algorithms, it receives, at best, lip service. Part of the reason is that doctors are unaware of the profound benefits achievable with lifestyle changes, and part of this unawareness stems from the guidelines lagging behind the …
Abstract P038: The Association Between Thyroid Function and Cardiac Structure and Function in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Georgina Gyarmati, Yuan Chen, John W McEvoy, Seth Martin, Anna Kottgen, Amil M Shah, Scott Solomon, Josef Coresh, Elizabeth Selvin, Kunihiro Matsushita
Journal: Circulation (2018)

Background: Most prior studies evaluating thyroid function and cardiac structure and function have been small and have not included the full spectrum of thyroid function hormones. Methods: Among 5122 ARIC participants (aged 66- 90 at the visit 5, 2011-2013) we evaluated the cross-sectional associations of clinical categories of thyroid function and thyroid hormone levels (triidothyronine [T3], thyroxine [T4], and thyroid-stimulating hormone [TSH]) with left ventricular structure, systolic function, and diastolic function based on echocardiogram after accounting for potential confounders including prevalent coronary heart disease and heart failure. Results: There were 417 participants (9.4%) with hypothyroidism and 155 participants (3.5%) with hyperthyroidism. Hypothyroidism tended to be associated with more echocardiographic parameters compared to hyperthyroidism. Among individual thyroid hormones, T3 was most robustly associated with left ventricular structure and function. Specifically, lower T3 level was associated with higher left ventricular mass and diameter and reduced systolic and diastolic dysfunction (Figure). Conclusions: In community-dwelling older adults, hypothyroidism was more evidently associated with altered left ventricular structure and function than hyperthyroidism. Among T3, T4, and TSH, lower T3 demonstrated most robust associations. Our findings highlight the importance of recognizing hypothyroidism for cardiac health and assessing T3 in addition to T4 and TSH for thyroid function assessment among older adults.
Advantages of Single-Nucleus over Single-Cell RNA Sequencing of Adult Kidney: Rare Cell Types and Novel Cell States Revealed in Fibrosis
Authors: Haojia Wu, Yuhei Kirita, Erinn L. Donnelly, Benjamin D. Humphreys
Journal: Journal of the American Society of Nephrology (2018)

Background A challenge for single-cell genomic studies in kidney and other solid tissues is generating a high-quality single-cell suspension that contains rare or difficult-to-dissociate cell types and is free of both RNA degradation and artifactual transcriptional stress responses. Methods We compared single-cell RNA sequencing (scRNA-seq) using the DropSeq platform with single-nucleus RNA sequencing (snRNA-seq) using sNuc-DropSeq, DroNc-seq, and 10X Chromium platforms on adult mouse kidney. We validated snRNA-seq on fibrotic kidney from mice 14 days after unilateral ureteral obstruction (UUO) surgery. Results A total of 11,391 transcriptomes were generated in the comparison phase. We identified ten clusters in the scRNA-seq dataset, but glomerular cell types were absent, and one cluster consisted primarily of artifactual dissociation – induced stress response genes. By contrast, snRNA-seq from all three platforms captured a diversity of kidney cell types that were not represented in the scRNA-seq dataset, including glomerular podocytes, mesangial cells, and endothelial cells. No stress response genes were detected. Our snRNA-seq protocol yielded 20-fold more podocytes compared with published scRNA-seq datasets (2.4% versus 0.12%, respectively). Unexpectedly, single-cell and single-nucleus platforms had equivalent gene detection sensitivity. For validation, analysis of frozen day 14 UUO kidney revealed rare juxtaglomerular cells, novel activated proximal tubule and fibroblast cell states, and previously unidentified tubulointerstitial signaling pathways. Conclusions snRNA-seq achieves comparable gene detection to scRNA-seq in adult kidney, and it also has substantial advantages, including reduced dissociation bias, compatibility with frozen samples, elimination of dissociation-induced transcriptional stress responses, and successful performance on inflamed fibrotic kidney.
Monitoring Disease Activity in Systemic Lupus Erythematosus With Single‐Molecule Array Digital Enzyme‐Linked Immunosorbent Assay Quantification of Serum Interferon‐α
Authors: Alexis Mathian, Suzanne Mouries‐Martin, Karim Dorgham, Hervé Devilliers, Laura Barnabei, Elyès Ben Salah, Fleur Cohen‐Aubart, Laura Garrido Castillo, Julien Haroche, Miguel Hie, Marc Pineton de Chambrun, Makoto Miyara, Delphine Sterlin, Micheline Pha, Du Lê Thi Huong, Frédéric Rieux‐Laucat, Flore Rozenberg, Guy Gorochov, Zahir Amoura
Journal: Arthritis & Rheumatology (2018)

No simple or standardized assay is available to quantify interferon-α (IFNα) in routine clinical practice. Single-molecule array (Simoa) digital enzyme-linked immunosorbent assay (ELISA) technology enables direct IFNα quantification at attomolar (femtogram per milliliter [fg/ml]) concentrations. This study was undertaken to assess IFNα digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity. IFNα concentrations in serum samples from 150 consecutive SLE patients in a cross-sectional study were determined with digital ELISA and a functional biologic activity assay (bioassay). According to their Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) flare composite scores, patients were divided into groups with inactive SLE (SLEDAI score of <4 or clinical SLEDAI score of 0) or active SLE (SLEDAI score of ≥4 or clinical SLEDAI score of >0), and into groups with no flare or mild/moderate flare or severe flare. Based on serum samples from healthy blood donors, the abnormal serum IFNα level threshold value was 136 fg/ml. Next, using receiver operating characteristic curves for an SLE patient series that was widely heterogeneous in terms of disease activity and organ involvement, the threshold IFNα value associated with active disease was determined to be 266 fg/ml. The digital ELISA-assessed serum IFNα level was a better biomarker of disease activity than the Farr assay because its specificity, likelihood ratio for positive results, and positive predictive value better discerned active SLE or flare from inactive disease. The digital ELISA was more sensitive than the bioassay for detecting low-abnormal serum IFNα concentrations and identifying patients with low disease activity. Direct serum IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti-IFNα treatment.
Association of Early Introduction of Solids With Infant Sleep
Authors: Chantal Dang, Lisa Hoyland, Ralph Nanan
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity
Authors: Pauline Morigny, Marianne Houssier, Aline Mairal, Claire Ghilain, Etienne Mouisel, Fadila Benhamed, Bernard Masri, Emeline Recazens, Pierre-Damien Denechaud, Geneviève Tavernier, Sylvie Caspar-Bauguil, Sam Virtue, Veronika Sramkova, Laurent Monbrun, Anne Mazars, Madjid Zanoun, Sandra Guilmeau, Valentin Barquissau, Diane Beuzelin, Sophie Bonnel, Marie Marques, Boris Monge-Roffarello, Corinne Lefort, Barbara Fielding, Thierry Sulpice, Arne Astrup, Bernard Payrastre, Justine Bertrand-Michel, Emmanuelle Meugnier, Laetitia Ligat, Frédéric Lopez, Hervé Guillou, Charlotte Ling, Cecilia Holm, Remi Rabasa-Lhoret, Wim H. M. Saris, Vladimir Stich, Peter Arner, Mikael Rydén, Cedric Moro, Nathalie Viguerie, Matthew Harms, Stefan Hallén, Antonio Vidal-Puig, Hubert Vidal, Catherine Postic, Dominique Langin
Journal: Nature Metabolism (2018)
Correlation of wtEGFR Activation Assessed by mAB806 Binding and EGFR Kinase Mutations in Stage IIIA N2 NSCLC
Authors: M.S. Liew, C. Murone, M. Walkiewicz, P. Mitchell, H. Gan, S. Barnett, P. Russell, G. Wright, A. Scott, T. John
Journal: Annals of Oncology (2012)
Peering Through the Haze of Smoked vs Vaporized Cannabis—To Vape or Not to Vape?
Authors: Nadia Solowij
Journal: JAMA Network Open (2018)

Tory R. Spindle, PhD; Edward J. Cone, PhD; Nicolas J. Schlienz, PhD; John M. Mitchell, PhD; George E. Bigelow, PhD; Ronald Flegel, MS; Eugene Hayes, PhD, MBA; Ryan Vandrey, PhD
Abstract 15999: Beyond Morbidity and Mortality: Academic Outcomes in Children With Congenital Heart Disease
Authors: Matthew Oster, Stephanie Watkins, Kevin Hill, Robert Meyer
Journal: Circulation (2015)

Introduction: While children with congenital heart disease (CHD) are known to have neurodevelopmental challenges, how these challenges translate to school performance is unknown. The purpose of our study was to compare the academic achievement of children with CHD to that of children without known birth defects. Hypothesis: Children with CHD would have lower standardized test performance scores and greater need for grade retention than their peers without birth defects. Methods: We performed a retrospective cohort study comparing educational outcomes for children born 1998-2003 with CHD, identified from the North Carolina (NC) Birth Defects Registry, vs. those without a known birth defect, randomly sampled from NC birth certificates. All children were linked to 3rd grade public school records from the NC Department of Public Instruction through 2012. We performed logistic regression to compare our outcomes of interest: a) meeting standards on the reading and math portions of 3rd grade End of Grade Testing, and b) 3rd grade retention. Models were adjusted for maternal education, public pre-K enrollment, and race/ethnicity. Results: Of the 5624 subjects with CHD and 10,832 with no birth defect, 51% and 60% were linked, respectively, to 3rd grade standard End of Grade testing records. Compared to children without a birth defect, those with CHD were more likely not to meet proficiency standards in reading (OR 1.4, 95% CI 1.3-1.6), math (OR 1.2, 95% CI 1.1-1.4), or both (OR 1.5, 95% CI 1.3-1.7). (Figure) Similarly, children with CHD were more likely to be retained in 3rd grade (2.8% vs. 1.9%, OR 1.4, 95% CI 1.1-1.9). Conclusions: Children with CHD have poorer educational achievement as compared to their peers without birth defects. History of CHD should be considered an important factor in determining a student’s need for specialized education services.
Frontline Therapy with Bendamustine and Rituximab (BR) in Follicular Lymphoma: Prognosis Among Patients with Progression of Disease By 24 Months (POD24) Is Poor with Majority Having Transformed Lymphoma
Authors: Ciara Louise Freeman, Kerry J Savage, Diego Villa, David W. Scott, Alina S. Gerrie, David J Ferguson, Fergus Cafferty, Graham W Slack, Pedro Farinha, Brian Skinnider, Joseph M. Connors, Laurie H Sehn
Journal: Blood (2018)
Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study
Authors: S. Adams, S. Loi, D. Toppmeyer, D.W. Cescon, M. De Laurentiis, R. Nanda, E.P. Winer, H. Mukai, K. Tamura, A. Armstrong, M.C. Liu, H. Iwata, L. Ryvo, P. Wimberger, H.S. Rugo, A.R. Tan, L. Jia, Y. Ding, V. Karantza, P. Schmid
Journal: Annals of Oncology (2018)

BackgroundStandard first-line treatment of metastatic triple-negative breast cancer (mTNBC) is chemotherapy. However, outcomes are poor, and new treatment options are needed. In cohort B of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as first-line therapy for patients with PD-L1-positive mTNBC.Patients and methodsEligible patients had centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, measurable disease at baseline per RECIST v1.1 by central review, no radiographic evidence of central nervous system metastases, and a tumor PD-L1 combined positive score ≥1. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. The primary end point was safety. Secondary end points included objective response rate, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), duration of response, progression-free survival and overall survival.ResultsAll 84 patients enrolled were women, and 73 (86.9%) received prior (neo)adjuvant therapy. Fifty-three (63.1%) patients had treatment-related adverse events (AEs), including 8 patients (9.5%) with grade 3 severity; no patients experienced grade 4 AEs or died because of treatment-related AEs. Four patients had a complete response and 14 had a partial response, for an objective response rate of 21.4% (95% CI 13.9–31.4). Of the 13 patients with stable disease, 2 had stable disease lasting ≥24 weeks, for a disease control rate of 23.8% (95% CI 15.9–34.0). At data cut-off, 8 of 18 (44.4%) responses were ongoing, and median duration of response was 10.4 months (range 4.2 to 19.2+). Median progression-free survival was 2.1 months (95% CI 2.0–2.2), and median overall survival was 18.0 months (95% CI 12.9–23.0).ConclusionsPembrolizumab monotherapy had a manageable safety profile and showed durable antitumor activity as first-line therapy for patients with PD-L1-positive mTNBC.Clinical trial registrationClinicalTrials.gov, NCT02447003.
Outpatient acupuncture effects on patient self-reported symptoms in oncology care: A retrospective analysis of real-world data.
Authors: Gabriel Lopez, M. Kay Garcia, Wenli Liu, Michael Spano, Susan Underwood, Janet L. Williams, Rocio Moguel, Yisheng Li, Seyedeh Dibaj, Eduardo Bruera, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2018)

135 Background: Increased access to complementary therapies such as acupuncture at academic medical centers has created new opportunities for management of cancer and cancer treatment related symptoms. Methods: Patients presenting for acupuncture treatment during calendar year 2016 at an outpatient integrative medicine clinic in a comprehensive cancer center were asked to complete a modified Edmonton Symptom Assessment Scale (ESAS; 16 symptoms, score 0-10, 10 worst possible) before and after each visit. ESAS subscales analyzed included global (GDS; score 0-90), physical (PHS, 0-60), and psychological distress (PSS, 0-20). ESAS symptom score change pre/post treatment and from baseline visit to first follow up were evaluated by paired t-test. Results: Of 375 participants [mean age 55.6, 68.3% female, 73.9% white, most common cancer diagnosis of breast (32.8%) and thoracic/head&amp;neck (25.9%)], 73.3% had at least one follow-up treatment [mean 4.6 (SD 5.1) treatments]. Highest/worst symptoms at baseline were poor sleep (3.92), fatigue (3.43), well-being (3.31), and pain (3.29). Statistically significant reduction/improvement (pre/post) was observed for all ESAS symptoms and subscales for the initial treatment (p &lt;0.001). Hot flashes had the highest mean reduction (-1.93), followed by fatigue (-1.72), numbness/tingling (-1.70), and nausea (-1.67). Clinically significant reductions were also observed for ESAS subscales of GDS (-12.2), PHS (-8.5), and PSS (-2.6). For symptom change from initial treatment to first follow-up (pre/pre), statistically and clinically significant improvement was observed for spiritual pain (-1.10; p&lt;0.001) and ESAS subscale of GDS (-6.09; p=0.048). Clinical response rates (reduction ≥1) on follow-up were highest for symptoms of spiritual pain (58.9%), dry mouth (57.8%) and nausea (57.3%). Conclusions: Outpatient acupuncture was associated with immediate and longitudinal significant improvement across a range of symptoms commonly experienced by individuals during cancer care. Further research is needed to better understand frequency of treatments needed in clinical practice to help maintain benefit.
Loss of ARHGEF1 causes a human primary antibody deficiency
Authors: Amine Bouafia, Sébastien Lofek, Julie Bruneau, Loïc Chentout, Hicham Lamrini, Amélie Trinquand, Marie-Céline Deau, Lucie Heurtier, Véronique Meignin, Capucine Picard, Elizabeth Macintyre, Olivier Alibeu, Marc Bras, Thierry Jo Molina, Marina Cavazzana, Isabelle André-Schmutz, Anne Durandy, Alain Fischer, Eric Oksenhendler, Sven Kracker
Journal: Journal of Clinical Investigation (2018)

ARHGEF1 is a RhoA-specific guanine nucleotide exchange factor expressed in hematopoietic cells. We used whole-exome sequencing to identify compound heterozygous mutations in ARHGEF1, resulting in the loss of ARHGEF1 protein expression in 2 primary antibody-deficient siblings presenting with recurrent severe respiratory tract infections and bronchiectasis. Both ARHGEF1-deficient patients showed an abnormal B cell immunophenotype, with a deficiency in marginal zone and memory B cells and an increased frequency of transitional B cells. Furthermore, the patients' blood contained immature myeloid cells. Analysis of a mediastinal lymph node from one patient highlighted the small size of the germinal centers and an abnormally high plasma cell content. On the molecular level, T and B lymphocytes from both patients displayed low RhoA activity and low steady-state actin polymerization (even after stimulation of lysophospholipid receptors). As a consequence of disturbed regulation of the RhoA downstream target Rho-associated kinase I/II (ROCK), the patients' lymphocytes failed to efficiently restrain AKT phosphorylation. Enforced ARHGEF1 expression or drug-induced activation of RhoA in the patients' cells corrected the impaired actin polymerization and AKT regulation. Our results indicate that ARHGEF1 activity in human lymphocytes is involved in controlling actin cytoskeleton dynamics, restraining PI3K/AKT signaling, and confining B lymphocytes and myelocytes within their dedicated functional environment.
Cancer patients’ perception of usefulness with wearable exercise tracker.
Authors: Amy Ng, Ekta Gupta, Swati Bansal, Rhodora C. Fontillas, Janet L. Williams, Seyedeh Dibaj, Eduardo Bruera
Journal: Journal of Clinical Oncology (2018)

51 Background: Wearable trackers (WT) are known for its popular use in healthy, active persons but limited studies have been conducted in cancer survivors. Methods: Participants were asked to wear the WT and synchronize data. Patients were asked to fill out questionnaire regarding their patient reported perceptions of the WT and their perception of usefulness of the WT. Results: 110 cancer patients were enrolled with 100 evaluable surveys. Median age of patients was 62 years old, females (60, 55%), white (79,73%), married/with significant other (77, 71%), with college education and above (51, 47%). There was no statistically significant association between demographic factors of age, gender, ethnicity, marital status, or education and the perception of usefulness of the WT. Eighty-four percent of outpatient (OP) and 67% of inpatient (IP) cancer patients perceived WT as useful, 96% OP and 94% IP reported wearing WT daily, 64% OP and 55% IP perceived WT as helping to increase physical activity and 76% OP and 59% IP would continue to wear WT after this study. For inpatients, ESAS score of pain (p value &lt;0.001), shortness of breath (p value &lt;0.0002) and feeling of well-being (p value &lt;0.001) improved over the course of rehabilitation. Improvement in FIM scores for transfers to wheelchair, walk assistance, walk distance, walking, stairs assistance, and stairs is significantly improved in rehabilitation (p value&lt;0.05). The average resting heart rate was 77 beats per minute and average number of steps per day was 1,863. For outpatients, the average resting heart rate was 77 beats per minute and average number of steps per day was 3,423. Patients who reported the WT as useful had significantly lower fatigue severity (3.3 vs. 6, p value&lt;0.05). Conclusions: Cancer patients perceived the WT as useful in both the inpatient and outpatient rehabilitation setting. No specific sub-group(s) of patients who expressed a higher level of agreement for usefulness of a wearable exercise tracker. There was an association between lower ESAS fatigue score and patient agreement of usefulness of the WT. These findings justify more research in WT and cancer rehabilitation. Clinical trial information: NCT03042884.