tbuckley/cabot-search huggingface dataset:
Concurrent Inhibition of Beta-Catenin/CBP and FLT3 Strongly Suppresses c-Myc and Synergistically Induces Apoptosis in FLT3 Mutant AML Cells
Authors: Xuejie Jiang, Po Yee Mak, Hong Mu, Weiguo Zhang, Duncan Mak, Peter Ruvolo, Teresa McQueen, Hongsheng Zhou, Jorge E. Cortes, Michael Andreeff, Bing Z Carter
Journal: Blood (2015)
Response to a Patient’s Failed Swallowing Study
Authors: Ross H. Albert
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine 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 Internal Medicine journal
Government Regulations on Physician Self-referral
Authors: Deepak A. Kapoor
Journal: JAMA (2015)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Tube Feeding in US Nursing Home Residents With Advanced Dementia, 2000-2014
Authors: Susan L. Mitchell, Vincent Mor, Pedro L. Gozalo, Joseph L. Servadio, Joan M. Teno
Journal: JAMA (2016)

feeding tubes decreased by approximately 50% between 2000 and 2014.This decline parallels the emergence of research, 1,2 expert opinion, and recommendations by national organizations 3 discouraging this practice.Feeding tube use decreased across racial groups, but remained relatively higher among black residents, consistent with prior research. 2,4 This study has limitations.The number of reported feeding tube insertions are specific to the cohort definitions.The actual number of tubes inserted in all US residents with advanced dementia is likely much higher.Moreover, the reported number of residents with advanced dementia and eating problems declined from 2000 to 2014, reflecting the shifting composition of US nursing homes, such that patients with chronic illnesses, including dementia, are being increasingly maintained in the community with greater access to services. 6However, given the analyses applied the same definitions to the numerator and denominator in each year, the comparison of annual insertion rates is reasonable.Power was inadequate to examine factors associated with tube feeding use.To ensure the message from existing evidence and expert recommendations is disseminated and disparities are reduced, fiscal and regulatory policies are needed that discourage tube feeding and promote a palliative approach to feeding problems in patients with advanced dementia.
An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer
Authors: Cheng S. Jin, Hironobu Wada, Takashi Anayama, Patrick Z. McVeigh, Hsin Pei Hu, Kentaro Hirohashi, Takahiro Nakajima, Tatsuya Kato, Shaf Keshavjee, David Hwang, Brian C. Wilson, Gang Zheng, Kazuhiro Yasufuku
Journal: Cancer Research (2016)

Abstract Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current nonsurgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460, and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon nonsurgical treatment of early-stage peripheral lung cancer. Cancer Res; 76(19); 5870–80. ©2016 AACR.
Abstract 3253: Metastasis suppression by non-KP54 kisspeptins
Authors: Kelsey R. Hampton, Keke M. Pounds, Andrew P. Tremblath, Danny R. Welch
Journal: Cancer Research (2015)

Abstract The KISS1 metastasis suppressor blocks metastasis by inhibiting colonization at secondary sites. KISS1 activity requires secretion and extracellular processing by furin into kisspeptins. Kisspeptin-54 (KP54; G68 to F121) binds a G-protein coupled receptor, KISS1R, and the mechanism of metastasis suppression has been assumed to be through the receptor. However, KISS1 is cleaved into kisspeptins outside of the cell, and KISS1R expression is not required for metastasis suppression. Therefore, an alternate hypothesis is that a non-KISS1R binding kisspeptin(s) is responsible for metastasis suppression. To test this hypothesis, we engineered all ten of the possible kisspeptins predicted from known dibasic cleavage sites (M1-Q145; M1-R56; M1-R67; M1-R124; R56-R67; G68-F121; E55-F121; E55-Q145; G68-Q145; E125-Q145) downstream of the KISS1 secretion signal peptide (designated KMP1 to KMP10, respectively) and expressed each individually in B16-F10 melanoma cells. Expression was confirmed by immunoblot and/or RT-QPCR analysis. Following intravenous injection, experimental lung metastases were quantified. KP54 expression suppressed metastasis. Some KMP lacking the KISS1R ligand suppressed metastasis as well as KP54 and full-length KISS1 (p&amp;lt;0.05). Specifically, the N-terminal kisspeptin (M1 - R56) dramatically suppressed metastasis. This suggests that the mechanism of action for metastasis suppression by KISS1 does not necessarily require activation of KISS1R by the peptide ligand but also leaves the possibility for additional receptors. Alternatively, KISS1/KMP interactions with other intracellular proteins may be required for metastasis suppressor activity. Support: CA134981, Natl Fndn Cancer Res, Komen SAC11037, KS Bioscience Auth, P30-CA168524, Steiner Family Fund. Citation Format: Kelsey R. Hampton, Keke M. Pounds, Andrew P. Tremblath, Danny R. Welch. Metastasis suppression by non-KP54 kisspeptins. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3253. doi:10.1158/1538-7445.AM2015-3253
Edoxaban versus enoxaparin–warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial
Authors: Andreas Goette, Jose L Merino, Michael D Ezekowitz, Dmitry Zamoryakhin, Michael Melino, James Jin, Michele F Mercuri, Michael A Grosso, Victor Fernandez, Naab Al-Saady, Natalya Pelekh, Bela Merkely, Sergey Zenin, Mykola Kushnir, Jindrich Spinar, Valeriy Batushkin, Joris R de Groot, Gregory Y H Lip
Journal: The Lancet (2016)
Growing large and fast: is infant growth relevant for the early origins of childhood asthma?
Authors: Liesbeth Duijts
Journal: Thorax (2016)

Early growth seems to be important for the risk of respiratory diseases in childhood and adulthood. A recent meta-analysis reported that low birth weight is associated with impaired lung function and asthma in childhood, and that these associations are partly explained by gestational age at birth.1 Low birth weight seems also associated with impaired lung function and increased risks of asthma and chronic obstructive airway disease in adulthood.2 Although birth weight is an important early growth measure and may reflect early development, it has important limitations. Birth weight is the end point of fetal growth and the beginning of infant growth.

Different prospective cohort studies have recently been set up to disentangle the association of early growth with respiratory diseases at later ages. A prospective birth cohort study showed that a higher fetal crown–rump length in first trimester was associated with a lower risk of wheezing, asthma and higher lung volumes.3 ,4 Also, a greater abdominal circumference during second half of pregnancy was associated with lower risk of atopic wheezing,5 whereas a higher femur length in second trimester was associated with lower risk of asthma.3 However, when individual fetal growth characteristics were combined into estimated fetal weight, associations of fetal weight growth with childhood wheezing or asthma were not consistent.4 ,6 ,7 Restricted fetal weight growth was associated with higher …
Tie1 controls angiopoietin function in vascular remodeling and inflammation
Authors: Emilia A. Korhonen, Anita Lampinen, Hemant Giri, Andrey Anisimov, Minah Kim, Breanna Allen, Shentong Fang, Gabriela D’Amico, Tuomas J. Sipilä, Marja Lohela, Tomas Strandin, Antti Vaheri, Seppo Ylä-Herttuala, Gou Young Koh, Donald M. McDonald, Kari Alitalo, Pipsa Saharinen
Journal: Journal of Clinical Investigation (2016)

The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, and vessel leakage. ANG1 is a Tie2 agonist that promotes vascular stabilization in inflammation and sepsis, whereas ANG2 is a context-dependent Tie2 agonist or antagonist. A limited understanding of ANG signaling mechanisms and the orphan receptor Tie1 has hindered development of ANG/Tie-targeted therapeutics. Here, we determined that both ANG1 and ANG2 binding to Tie2 increases Tie1-Tie2 interactions in a β1 integrin-dependent manner and that Tie1 regulates ANG-induced Tie2 trafficking in endothelial cells. Endothelial Tie1 was essential for the agonist activity of ANG1 and autocrine ANG2. Deletion of endothelial Tie1 in mice reduced Tie2 phosphorylation and downstream Akt activation, increased FOXO1 nuclear localization and transcriptional activation, and prevented ANG1- and ANG2-induced capillary-to-venous remodeling. However, in acute endotoxemia, the Tie1 ectodomain that is responsible for interaction with Tie2 was rapidly cleaved, ANG1 agonist activity was decreased, and autocrine ANG2 agonist activity was lost, which led to suppression of Tie2 signaling. Tie1 cleavage also occurred in patients with hantavirus infection. These results support a model in which Tie1 directly interacts with Tie2 to promote ANG-induced vascular responses under noninflammatory conditions, whereas in inflammation, Tie1 cleavage contributes to loss of ANG2 agonist activity and vascular stability.
Phase II trial of figitumumab in patients with refractory, metastatic colorectal cancer (mCRC).
Authors: C. Becerra, R. Salazar, R. Garcia-Carbonero, A. L. Thomas, F. Vázquez-Mazón, J. Cassidy, T. Maughan, M. Gallén, T. Iveson, M. Hixon, A. Gualberto, D. Yin, E. K. Bergsland, D. Li
Journal: Journal of Clinical Oncology (2011)

3525 Background: Figitumumab (F; CP-751,871) is a fully human monoclonal antibody (mAb) that inhibits IGF-IR. This phase II trial examined the efficacy and safety of F in patients (pts) with refractory mCRC. Methods: Pts (male or female) had an ECOG PS of 0 or 1, and had received prior chemotherapy (+/– mAb therapy). Cohort A received intravenous (iv) F 20 mg/kg q3w. Following a protocol amendment a further cohort received iv F 30 mg/kg q3w (Cohort B). F was dosed on days 1 and 2 of cycle 1 (loading dose) and on day 1 of each subsequent cycle. The primary endpoint was 6-month overall survival (6-mo OS). Hypothesis: H0 p=.45 (p=probability of 6-mo OS) vs. H1 p>.45. Secondary endpoints included safety, PFS, OS, and PK. Associations between plasma levels of free-IGF-1 (fIGF-1) and OS were examined. Results: 168 pts (Cohort A n=85; Cohort B n=83) were treated. Pts were heavily pretreated: 76% (Cohort A) and 77% (Cohort B) had received ≥3 prior systemic regimes. The probability of 6-mo OS was not significantly greater than .45 for either cohort (Table). There was a trend toward longer median OS in pts with high levels of fIGF-1 (Table). The most common grade 3/4 non-hematologic AEs in Cohort A were hyperglycemia (16%), asthenia (13%), and fatigue (6%), and in Cohort B hyperglycemia (22%) and asthenia (13%). The most common hematologic abnormalities in both cohorts were lymphopenia (Cohort A 6%; Cohort B 4%) and anemia (Cohort A 5%; Cohort B 3%). Overall, F 20 mg/kg was better tolerated than F 30 mg/kg. Plasma concentrations of F suggest that a loading dose of F facilitated early achievement of steady state concentrations in Cycle 1. Conclusions: 6-mo OS results do not support further study of F 20 or 30 mg/kg in pts with refractory mCRC. In both cohorts there was a trend toward longer median OS in pts with high levels of fIGF-1. Cohort A n=85 Cohort B n=83 6-mo OS, % (95% CI) 49.4 (38.8, 60.0) 44.1 (33.4, 54.9) Median PFS, mos (95% CI) 1.4 (1.3, 1.8) 1.4 (1.3, 1.8) Median OS, mos (95% CI) 5.8 (4.3, 7.1) 5.6 (4.1, 6.9) Median OS by fIGF-1 status*, mos (95% CI) fIGF-1 low n=48 fIGF-1 high n=34 fIGF-1 low n=47 fIGF-1 high n=23 5.0 (2.6, 6.6) 6.7 (4.2, 11.9) 3.8 (2.9, 5.6) 5.9 (3.6, 8.3) HR (95% CI) 0.68 (0.43, 1.07) HR (95% CI) 0.65 (0.38, 1.12) *fIGF-1 low = <1.0 ng/mL; fIGF-1 high = ≥1.0 ng/mL.
Fixed-dose combination and therapeutic drug monitoring in tuberculosis: friend or foe?
Authors: Marlanka A. Zuur, Onno W. Akkerman, Lina Davies Forsman, Yi Hu, Rongdong Zheng, Judith Bruchfeld, Simon Tiberi, Giovanni Battista Migliori, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2016)

Tuberculosis (TB) remains one of the world's deadliest infectious diseases. The World Health Organization (WHO) estimated that, in 2014 alone, 9.6 million people fell ill with TB and 1.5 million died due to the disease [1]. South-East Asia and Western Pacific Regions accounted for 58% of these [1]. As most deaths from TB can now be prevented, efforts must be accelerated to ensure the targets of the Sustainable Development Goals are reached [1]. Fixed-dose combination and therapeutic drug monitoring can be combined in programmatic treatment of tuberculosis <http://ow.ly/sCtd302h0Ka>
Association of Insulin Resistance and Glycemic Metabolic Abnormalities With LV Structure and Function in Middle Age
Authors: Satoru Kishi, Samuel S. Gidding, Jared P. Reis, Laura A. Colangelo, Bharath A. Venkatesh, Anderson C. Armstrong, Akihiro Isogawa, Cora E. Lewis, Colin Wu, David R. Jacobs, Kiang Liu, João A.C. Lima
Journal: JACC. Cardiovascular imaging (2016)
ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells
Authors: Chandra Sekhar Boddupalli, Shiny Nair, Simon M. Gray, Heba N. Nowyhed, Rakesh Verma, Joanna A. Gibson, Clara Abraham, Deepak Narayan, Juan Vasquez, Catherine C. Hedrick, Richard A. Flavell, Kavita M. Dhodapkar, Susan M. Kaech, Madhav V. Dhodapkar
Journal: Journal of Clinical Investigation (2016)

Immune surveillance in tissues is mediated by a long-lived subset of tissue-resident memory T cells (Trm cells). A putative subset of tissue-resident long-lived stem cells is characterized by the ability to efflux Hoechst dyes and is referred to as side population (SP) cells. Here, we have characterized a subset of SP T cells (Tsp cells) that exhibit a quiescent (G0) phenotype in humans and mice. Human Trm cells in the gut and BM were enriched in Tsp cells that were predominantly in the G0 stage of the cell cycle. Moreover, in histone 2B-GFP mice, the 2B-GFP label was retained in Tsp cells, indicative of a slow-cycling phenotype. Human Tsp cells displayed a distinct gene-expression profile that was enriched for genes overexpressed in Trm cells. In mice, proteins encoded by Tsp signature genes, including nuclear receptor subfamily 4 group A member 1 (NR4A1) and ATP-binding cassette (ABC) transporters, influenced the function and differentiation of Trm cells. Responses to adoptive transfer of human Tsp cells into immune-deficient mice and plerixafor therapy suggested that human Tsp cell mobilization could be manipulated as a potential cellular therapy. These data identify a distinct subset of human T cells with a quiescent/slow-cycling phenotype, propensity for tissue enrichment, and potential to mobilize into circulation, which may be harnessed for adoptive cellular therapy.
Pregnancy-associated breast cancer: Characterization and potential chemoprevention with anti-inflammatory treatment.
Authors: V. F. Borges, T. Lyons, J. O'Brien, S. Jindal, P. J. Schedin
Journal: Journal of Clinical Oncology (2010)

10645 Background: Pregnancy-associated breast cancer (PABC) is a subset of breast cancer with higher metastatic potential, and the poorest survival is observed in women diagnosed post-partum but within 6 years of birth. We have proposed the involution-hypothesis to account for this increased risk: the involuting microenvironment of the breast supports dissemination of pre-existing but previously quiescent tumor. Methods: To address whether PABC is characterized by specific histologic or biologic subtypes we have obtained 86 cases of post-partum PABC and 141 controls. A trend was noted towards increased lobular cancers in the PABC group of 16.2% v 9.2% non-PABC. Biologic subtype did not differ between PABC and non-PABC with Luminal at 62.7% v 57.4%, Her 2 at 6.9% v 7.0%, and Triple negative at 13.9% v. 14.8%. These data suggest the poor prognosis of PABC is independent of subtype. Study of additional prognostic markers is ongoing. To investigate the role of the involuting microenvironment on tumor progression we established a novel model for PABC. HumanMCF-10DCIS cells were injected into SCID mice whose mammary glands were quiescent (nulliparous group) or actively involuting (involution group). Results: As compared to the nulliparous group, primary tumor incidence, size, and multiplicity were significantly increased in the involution group. Increased local tumor dissemination into surrounding tissue and peritumoral vessels, as well as, increased cell seeding to the lung was observed in the involution group. Primary tumor cells isolated from involution group tumors demonstrated increased in vitro invasive potential, which were reversed when cells were treated with Cox-2 specific inhibitor, celecoxib. Treatment of the mice with ibuprofen resulted in decreased tumor size and cell seeding to the lung in the involution group only. Conclusions: These data support the hypothesis that the increased metastatic potential of human PABC is not driven by alteration in biologic subtype but rather the event of involution is the key for metastatic increase observed in PABC. Finally, intervention with anti-inflammatory treatment during involution may reduce risk of metastasis associated with PABC. No significant financial relationships to disclose.
Maternal Folate Intake during Pregnancy and Childhood Asthma in a Population-based Cohort
Authors: Christine L. Parr, Maria C. Magnus, Øystein Karlstad, Margaretha Haugen, Helga Refsum, Per M. Ueland, Adrian McCann, Per Nafstad, Siri E. Håberg, Wenche Nystad, Stephanie J. London
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

A potential adverse effect of high folate intake during pregnancy on children's asthma development remains controversial.To prospectively investigate folate intake from both food and supplements during pregnancy and asthma at age 7 years when the diagnosis is more reliable than at preschool age.This study included eligible children born 2002-2006 from the Norwegian Mother and Child Cohort Study, a population-based pregnancy cohort, linked to the Norwegian Prescription Database. Current asthma at age 7 was defined by asthma medications dispensed at least twice in the year (1,901 cases; n = 39,846) or by maternal questionnaire report (1,624 cases; n = 28,872). Maternal folate intake was assessed with a food frequency questionnaire validated against plasma folate. We used log-binomial and multinomial regression to calculate adjusted relative risks with 95% confidence intervals.Risk of asthma was increased in the highest versus lowest quintile of total folate intake with an adjusted relative risk of 1.23 (95% confidence interval, 1.06-1.44) that was similar for maternally reported asthma. Mothers in the highest quintile had a relatively high intake of food folate (median, 308; interquartile range, 241-366 μg/d) and nearly all took at least 400 μg/d of supplemental folic acid (median, 500; interquartile range, 400-600 μg/d).In this large prospective population-based cohort with essentially complete follow-up, pregnant women taking supplemental folic acid at or above the recommended dose, combined with a diet rich in folate, reach a total folate intake level associated with a slightly increased risk of asthma in children.