tbuckley/cabot-search huggingface dataset:
Abstract 2: Historical Trends in Kawasaki Disease over Three Decades in a Single Institution
Authors: Annette L Baker, Kimberly Gauvreau, Alexander Tang, Sarah D de Ferranti, Kevin G Friedman, David R Fulton, Jane W Newburger
Journal: Circulation (2015)

Purpose: Kawasaki disease (KD) awareness and therapy have evolved since its description in 1967. We explored historical trends since 1984 in patients (pts) treated for KD at a single institution. Methods: Inclusion criteria were 1) first episode of KD, and 2) treated with IVIG within 3 weeks of illness onset. Exclusion criteria were 1) evaluation solely for a second opinion, and 2) presence of congenital heart disease. We reviewed age at diagnosis, sex, race, presence of complete vs. incomplete (fever + &lt;4 clinical criteria), days of fever at initial IVIG treatment, and incidence of retreatment. Changes in pt characteristics over time were evaluated using tests of trends. Results: Of 1739 pts, 1133 met eligibility criteria. Race included 61% White, 10% Black, 11% Asian: 6% other, and 12% unknown. At diagnosis, 16% were age &lt;1 years (yrs), 58% were 1&lt;5 yrs, 24% were 5&lt;12 yrs, and 2% were ≥12 yrs. The median age at fever onset was 3 yrs and has not changed significantly over time. Male to female ratio was 59% to 41% and was stable over time. Median fever duration before IVIG treatment in the whole cohort was 7 days. Within the complete vs. incomplete KD groups, illness day at treatment was stable over time. However, median days of fever before IVIG treatment were lower in pts with complete vs. incomplete criteria (6 vs. 8 days, respectively, p&lt;.001). The % of pts treated with IVIG for incomplete KD increased significantly over time. Before 1989, only 1 pt (2%) was treated with IVIG for incomplete KD. From 1990-1994, 11 pts (15%) pts had incomplete criteria, whereas from 2010-2014, 45 pts (27%) received IVIG treatment with incomplete clinical criteria (p=.001). The incidence of retreatment with IVIG also increased, from 9% (1984-1989) to 23% (2010-2014, p&lt;.001). The use of adjunctive therapies (i.e., steroids, cyclosporine, cytoxan, abciximab and/or infliximab) were documented in 104/1133 pts (9%) and increased over time (p&lt;.001). Conclusions: At a single center over 3 decades, treatment of incomplete KD, as well as retreatment with IVIG and use of adjunctive therapies have become increasingly common. Pts who had incomplete diagnostic criteria received IVIG later in their illness. Future studies should assess whether these secular trends have improved outcomes in pts with KD.
Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open‐Label Trial
Authors: Raimon Sanmarti, Douglas J. Veale, Emilio Martin‐Mola, Alejandro Escudero‐Contreras, Carlos González, Liliana Ercole, Rocío Alonso, João E. Fonseca
Journal: Arthritis & Rheumatology (2019)

Objective To evaluate the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab (TCZ‐SC) in patients with rheumatoid arthritis (RA) who are in clinical remission. Methods RA patients with active disease and an inadequate response to conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) or to a biologic agent were entered into a single‐arm treatment phase with 162 mg of TCZ‐SC administered once weekly (TCZ‐SC 162 mg qw) as monotherapy or in combination with a csDMARD for 24 weeks. Patients who achieved clinical remission at weeks 20 and 24 were randomized to continue with the same regimen or to switch to 162 mg TCZ‐SC administered every 2 weeks (TCZ‐SC 162 mg q2w) for 24 weeks (open‐label). Patients with a Disease Activity Score in 28 joints (DAS28) of &lt;2.6 were considered to be in clinical remission. Results In total, 179 (45%) of 401 patients in the single‐arm phase achieved clinical remission and were randomized to continue to receive TCZ‐SC 162 mg qw (n = 89) or to switch to TCZ‐SC 162 mg q2w (n = 90) for 24 weeks. At week 48, significantly more patients treated with TCZ‐SC 162 mg qw remained in clinical remission compared to patients who received TCZ‐SC 162 mg q2w (90% versus 73%; P = 0.004). The results of other efficacy measures revealed greater efficacy with TCZ‐SC 162 mg qw, but none of the efficacy outcomes in this group were significantly different from those in patients treated with TCZ‐SC 162 mg q2w, except for the mean change from baseline in the DAS28 score at week 48 (mean change −4.07 points [SD 1.29] versus −3.65 points [SD 1.35]; P = 0.034). Tolerability and safety parameters were similar between the treatment groups. Conclusion Increasing the dose interval of TCZ‐SC in patients with RA was associated with a lower likelihood of maintaining remission after 24 weeks and was not associated with better tolerability. However, most patients were able to sustain remission with a half‐dose of TCZ‐SC, and therefore this strategy deserves further investigation.
Abstract 15142: Endogenous Cardiac Stem Cells’ Activation in Response to Injury Potentiates Their Regenerative Ability
Authors: Andrew J Smith, Iolanda Aquila, Beverley J Henning, Mariangela Scalise, Bernardo Nadal-Ginard, Georgina M Ellison, Daniele Torella
Journal: Circulation (2015)

The identification of resident, endogenous cardiac stem cells (eCSCs) has re-shaped our understanding of cardiac cellular physiology, while offering a significant potential therapeutic avenue. The biology of these cells must be better understood to harness their potential benefits. We used an acute dose (s.c.; 5mgkg-1) of isoproterenol (ISO) to induce diffuse cardiac injury, with associated eCSC activation, in rats. As peak eCSC activation was at 24 hours post ISO-injury, c-kitpos eCSCs were isolated, characterised and their potential for growth and regenerative potential was assessed in vitro and in vivo, respectively. Activated eCSCs showed increased cell cycling activity (51+1% in S- or G2/M phases vs. 9+2% of quiescent), Ki67 expression (56+7% vs. 10+1%) and TERT expression (14-fold increase vs. quiescent). When directly harvested in culture, activated eCSCs showed augmented proliferation, clonogenicity and cardiosphere formation compared to quiescent eCSCs. Activated eCSCs showed increases in expression of numerous growth factors, particularly HGF, IGF-1, TGF-β, periostin, PDGF-AA and VEGF-A. Furthermore, significant alterations were found in the miRnome, notably increased miR-146b and -221, and decreased miR-192 and -351. ISO+5FU was administrated to mice to induce a model of chronic dilated cardiomyopathy, which is characterized by the ablation of eCSCs and the absence of cardiomyocyte replenishment. In these mice with chronic heart failure, freshly isolated quiescent eCSCs or activated eCSCs (2d post-ISO) were injected through the tail vein. 28 days after injection, activated but not quiescent eCSCs re-populated the resident CSC pool, promoted robust new cardiomyocyte formation and improved cardiac function when compared to saline-treated mice. Dual-labelling with BrdU and EdU at selected stages after ISO injury determined that activated eCSCs returned to a quiescent level by 10 weeks post-injury. In conclusion, CSCs rapidly switch from a quiescent to an activated state to match the myocardial needs for myocyte replacement after injury and then spontaneously go back to quiescence. Harnessing the molecules regulating this process may open up future novel approaches for effective myocardial regeneration.
Abstract 18106: Estimation of Incident Heart Failure Risk in US Hispanics/Latinos Using a Validated Echocardiographic Risk Stratification Index: Echo Study of Latinos
Authors: Maria O Rangel, Robert C Kaplan, Martha L Daviglus, Dalane W Kitzman, Mayank Kansal, Daniel M Spevack, Ajit Raisinghani, Sanjiv J Shah, Carlos J Rodriguez
Journal: Circulation (2016)

Introduction: Based on the prevalence of cardiovascular risk factors, Hispanics/Latinos are considered at risk for symptomatic heart failure (HF). Nonetheless, there is a gap of information regarding the future impact of this population in the anticipated HF epidemic in the US. Methods: Cross-sectional data derived from the Echo-Study of Latinos (ECHO-SOL) on participants older than 45 years of age without a history of symptomatic HF. The validated Echocardiographic Risk Stratification Index (ERSI) derived from echocardiographic parameters (LVMI, LAVI, mitral regurgitation grade, LVOT-VTI, presence of diastolic dysfunction) was applied to estimate incident HF risk. The index range was 0 to 8, with lower scores representing lower risk. The cohort was divided in two subpopulations: Low Risk (ERSI <3) and High Risk (ERSI ≥3). Survey statistics and weighted frequencies were used. Results: 1,769 participants [57% women, mean age 56.3 (±0.37)] were included. The High Risk subpopulation represented 50.4% of the ...
Neutrophil Extracellular Traps Enhance Procoagulant Activity in Patients with Oral Squamous Cell Carcinoma
Authors: Baorong Li, Yingmiao Liu, Cong Zhang, Yan Kou, Lili Zou, Hui Liang, Li Hou, Tao Li, Yan Zhang, Nan Zuo, Wenhui Liu, Jialan Shi, Tenglong Hu
Journal: Blood (2018)
NOX4 is a major regulator of cord blood-derived endothelial colony-forming cells which promotes post-ischaemic revascularization
Authors: Karla M O’Neill, David C Campbell, Kevin S Edgar, Eleanor K Gill, Arya Moez, Kiran J McLoughlin, Christina L O’Neill, Margaret Dellett, Ciarán J Hargey, Rawan A Abudalo, Michael O’Hare, Philip Doyle, Tinrui Toh, Joshua Khoo, June Wong, Cian M McCrudden, Marco Meloni, Coy Brunssen, Henning Morawietz, Mervin C Yoder, Denise M McDonald, Chris J Watson, Alan W Stitt, Andriana Margariti, Reinhold J Medina, David J Grieve
Journal: Cardiovascular Research (2019)

Cord blood-derived endothelial colony-forming cells (CB-ECFCs) are a defined progenitor population with established roles in vascular homeostasis and angiogenesis, which possess low immunogenicity and high potential for allogeneic therapy and are highly sensitive to regulation by reactive oxygen species (ROS). The aim of this study was to define the precise role of the major ROS-producing enzyme, NOX4 NADPH oxidase, in CB-ECFC vasoreparative function.In vitro CB-ECFC migration (scratch-wound assay) and tubulogenesis (tube length, branch number) was enhanced by phorbol 12-myristate 13-acetate (PMA)-induced superoxide in a NOX-dependent manner. CB-ECFCs highly-expressed NOX4, which was further induced by PMA, whilst NOX4 siRNA and plasmid overexpression reduced and potentiated in vitro function, respectively. Increased ROS generation in NOX4-overexpressing CB-ECFCs (DCF fluorescence, flow cytometry) was specifically reduced by superoxide dismutase, highlighting induction of ROS-specific signalling. Laser Doppler imaging of mouse ischaemic hindlimbs at 7 days indicated that NOX4-knockdown CB-ECFCs inhibited blood flow recovery, which was enhanced by NOX4-overexpressing CB-ECFCs. Tissue analysis at 14 days revealed consistent alterations in vascular density (lectin expression) and eNOS protein despite clearance of injected CB-ECFCs, suggesting NOX4-mediated modulation of host tissue. Indeed, proteome array analysis indicated that NOX4-knockdown CB-ECFCs largely suppressed tissue angiogenesis, whilst NOX4-overexpressing CB-ECFCs up-regulated a number of pro-angiogenic factors specifically-linked with eNOS signalling, in parallel with equivalent modulation of NOX-dependent ROS generation, suggesting that CB-ECFC NOX4 signalling may promote host vascular repair.Taken together, these findings indicate a key role for NOX4 in CB-ECFCs, thereby highlighting its potential as a target for enhancing their reparative function through therapeutic priming to support creation of a pro-reparative microenvironment and effective post-ischaemic revascularization.
Abstract 1114: The Role of Myocardial Glut4 in Ischemia-Reperfusion Injury
Authors: John W Elrod, Kirsten Hartil, Mark R Duranski, Ariana Fiallo, Maureen J Charron, David J Lefer
Journal: Circulation (2006)

Background: Mice with global ablation of glucose transporter-4 (Glut4−/−) are insulin resistant, have normal cardiac glucose uptake, increased glycogen synthesis, decreased expression of fatty acid...
Dexterous Hand Movements and Their Recovery After Central Nervous System Injury
Authors: Tadashi Isa
Journal: Annual Review of Neuroscience (2019)

Hand dexterity has uniquely developed in higher primates and is thought to rely on the direct corticomotoneuronal (CM) pathway. Recent studies have shown that rodents and carnivores lack the direct CM pathway but can control certain levels of dexterous hand movements through various indirect CM pathways. Some homologous pathways also exist in higher primates, and among them, propriospinal (PrS) neurons in the mid-cervical segments (C3-C4) are significantly involved in hand dexterity. When the direct CM pathway was lesioned caudal to the PrS and transmission of cortical commands to hand motoneurons via the PrS neurons remained intact, dexterous hand movements could be significantly recovered. This recovery model was intensively studied, and it was found that, in addition to the compensation by the PrS neurons, a large-scale reorganization in the bilateral cortical motor-related areas and mesolimbic structures contributed to recovery. Future therapeutic strategies should target these multihierarchical areas.
Collaborative Telerehabilitation—A Smart Move for Patients With Advanced Cancer
Authors: Manali I. Patel
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3
Authors: Yi Niu, Ziyou Lin, Arabella Wan, Honglei Chen, Heng Liang, Lei Sun, Yuan Wang, Xi Li, Xiao-feng Xiong, Bo Wei, Xiaobin Wu, Guohui Wan
Journal: Molecular Cancer (2019)

N6-methyladenosine (m6A) modification is the most pervasive modification in mRNA, and has been considered as a new layer of epigenetic regulation on mRNA processing, stability and translation. Despite its functional significance in various physiological processes, the role of the m6A modification involved in breast cancer is yet fully understood. We used the m6A-RNA immunoprecipitation sequencing to identify the potential targets in breast cancer. To determine the underlying mechanism for the axis of FTO-BNIP3, we performed a series of in vitro and in vivo assays in 3 breast cancer cell lines and 36 primary breast tumor tissues and 12 adjunct tissues. We showed that FTO, a key m6A demethylase, was up-regulated in human breast cancer. High level of FTO was significantly associated with lower survival rates in patients with breast cancer. FTO promoted breast cancer cell proliferation, colony formation and metastasis in vitro and in vivo. We identified BNIP3, a pro-apoptosis gene, as a downstream target of FTO-mediated m6A modification. Epigenetically, FTO mediated m6A demethylation in the 3'UTR of BNIP3 mRNA and induced its degradation via an YTHDF2 independent mechanism. BNIP3 acts as a tumor suppressor and is negatively correlated with FTO expression in clinical breast cancer patients. BNIP3 dramatically alleviated FTO-dependent tumor growth retardation and metastasis. Our findings demonstrate the functional significance of the m6A modification in breast cancer, and suggest that FTO may serve as a novel potential therapeutic target for breast cancer.
Long Noncoding RNA <i>ELIT-1</i> Acts as a Smad3 Cofactor to Facilitate TGFβ/Smad Signaling and Promote Epithelial–Mesenchymal Transition
Authors: Satoshi Sakai, Tatsuya Ohhata, Kyoko Kitagawa, Chiharu Uchida, Takuya Aoshima, Hiroyuki Niida, Tetsuro Suzuki, Yasumichi Inoue, Keiji Miyazawa, Masatoshi Kitagawa
Journal: Cancer Research (2019)

TGFβ is involved in various biological processes, including development, differentiation, growth regulation, and epithelial-mesenchymal transition (EMT). In TGFβ/Smad signaling, receptor-activated Smad complexes activate or repress their target gene promoters. Smad cofactors are a group of Smad-binding proteins that promote recruitment of Smad complexes to these promoters. Long noncoding RNAs (lncRNA), which behave as Smad cofactors, have thus far not been identified. Here, we characterize a novel lncRNA EMT-associated lncRNA induced by TGFβ1 (ELIT-1). ELIT-1 was induced by TGFβ stimulation via the TGFβ/Smad pathway in TGFβ-responsive cell lines. ELIT-1 depletion abrogated TGFβ-mediated EMT progression and expression of TGFβ target genes including Snail, a transcription factor critical for EMT. A positive correlation between high expression of ELIT-1 and poor prognosis in patients with lung adenocarcinoma and gastric cancer suggests that ELIT-1 may be useful as a prognostic and therapeutic target. RIP assays revealed that ELIT-1 bound to Smad3, but not Smad2. In conjunction with Smad3, ELIT-1 enhanced Smad-responsive promoter activities by recruiting Smad3 to the promoters of its target genes including Snail, other TGFβ target genes, and ELIT-1 itself. Collectively, these data show that ELIT-1 is a novel trans-acting lncRNA that forms a positive feedback loop to enhance TGFβ/Smad3 signaling and promote EMT progression. SIGNIFICANCE: This study identifies a novel lncRNA ELIT-1 and characterizes its role as a positive regulator of TGFβ/Smad3 signaling and EMT.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/11/2821/F1.large.jpg.
Analysis of Toxic Effects With Antiangiogenic Agents Plus Stereotactic Body Radiation in Ultracentral Lung Tumors
Authors: Chunyu Wang, Andreas Rimner, Daphna Y. Gelblum, Jessica Flynn, Andrew Jackson, Ellen Yorke, Abraham J. Wu
Journal: JAMA Oncology (2019)

special diets (29 of 1023, 2.9%), acupuncture (26 of 1023, 2.0%), homeopathy (15 of 1023, 1.5%), movement or exercise techniques (11 of 1023, 1.3%), naturopathy (7 of 1023, 0.6%), traditional healers (6 of 1023, 0.4%), energy healing therapy (5 of 1023, 0.6%), biofeedback (5 of 1023, 0.4%), hypnosis (4 of 1023, 0.5%), and craniosacral therapy (2 of 1023, 0.2%).Factors associated with CAM use included white race (AOR, 1.82; 95% CI, 1.28-2.58;P = .001),female sex (AOR, 1.55; 95% CI, 1.26-1.91;P < .001),non-Hispanic ethnicity (AOR, 1.64; 95% CI, 1.05-2.56;P = .03),and younger age (AOR, 1.02 per year; 95% CI, 1.01-1.02;P < .001)(Table 1).Among 1023 participants using CAM, 288 (29.3%) did not disclose CAM use to their physicians.The adjusted rates of nondisclosure for those using herbal supplements was 11.8% and 58.2% for those using mantra/mindfulness/spiritual meditation (Table 2).The most frequently reported reasons for nondisclosure were because the physician did not ask (n = 155 of 288; 57.4%) or participants did not think their physicians needed to know (n = 140 of 288; 47.4%).A smaller proportion of CAM users felt that their physician did not know as much about the therapy (n = 28 of 288; 8.5%), reported they were not given enough time to tell about therapy (n = 12 of 288; 5.7%), expressed concern about a negative reaction (n = 17 of 288; 3.9%), were worried that their physician would discourage use (n = 18 of 288; 3.6%), or reported that physicians discouraged use in the past (n = 11 of 288; 1.9%).When the cohort was restricted to 812 patients with cancer diagnosed up to 2 years prior to survey administration, 271 (33.4%) reported CAM use, including 231 (28.5%) who did not disclose CAM use to their physician.Discussion | In this comprehensive national study, 1023 of 3118 (33.3%) participants with a history of cancer reported CAM use in the past year, 288 (29.3%) of whom did not disclose use of CAM to their physician.Individuals diagnosed with cancer may have many motivations for seeking CAM, including persistent symptoms, psychological distress, or to gain a sense of control over their care. 6 Given the high proportion of patients with cancer and cancer survivors reporting use of CAM in this nationally representative sample, the potential implications of CAM use on oncologic outcomes merits further study.Policy and guidelines should be established to encourage discussion of CAM.Data for this study were collected in 2012; however, this time frame is within those available from other nationwide databases.The NHIS is a US database, thus our results may not be generalizable to international populations.
Validation of BRCA mutation-carrier probability model, BRCAPRO, in Japanese.
Authors: Masahiro Ito, Yuri Yasuda, Akihiko Furuta, Noriaki Ohuchi
Journal: Journal of Clinical Oncology (2013)

e12532 Background: Genetic testing has not been widely performed in Japan. It is not known whether BRCA mutation-carrier model is useful for selecting eligible person of genetic testing. We studied the validation of BRCAPRO in Japanese. Methods: Twenty-six hundred sixty-five people visited to our hospital between 2011 and 2012.They were surveyed family history as a risk factor of inheriting breast cancer according to NCCN guideline. Among them, those who have a number of family history of breast cancer, ovarian cancer, pancreatic cancer, prostate cancer were selected and in addition, genetic counselor constructed family tree. We also calculated BRCA1/2 mutation probability by BRCAPRO.Those who had more than 10% mutation probability and early onset breast cancer, triple negative breast cancer were received genetic counseling and genetic testing for applicants. We also calculated sensitivity, specificity and predictive value at 10% estimated probability. Results: One hundred five people (3.9%) were selected as a risk of inheriting breast cancer, of which sixty-three people (2.3%) were constructed family tree.The number of people who had more than 10% and 30% mutation probability by BRCAPRO was seven (0.26%) and three (0.11%).Nine people performed BRCA1/2 genetic testing (proband : eight, relative: one)Four people carried a deleterious BRCA mutation (BRCA1: three, BRCA2: one).In the cases which had more than 30% mutation probability, all of them carried a deleterious BRCA mutation. Most of their mutation site was L63X which was most frequent in Japan. Using a 10% cut-off, sensitivity was 75%, specificity was 80%,positive predictive value was 75%. When it comes to the cases which had more than 30% mutation probability, Sensitivity, specificity, positive predictive value were all 100%. Conclusions: Our findings suggest BRCAPRO is useful in Japanese, especially those who have more than 30% mutation probability.