tbuckley/cabot-search huggingface dataset:
I Thought You Said This Was Confidential?—Challenges to Protecting Privacy for Teens and Young Adults
Authors: Lauren E. Wisk, Susan H. Gray, Holly C. Gooding
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
Transgenic mice with mouse EGFR mutation developed lung adenocarcinoma
Authors: Kadoaki Ohashi, Kannmei Rai, Katsuyuki Kiura, Masahiro Osawa, Seiki Hirano, Yoshiro Fujiwara, Tadashi Yoshino, Nagio Takigawa, Minoru Takata, Mitsune Tanimoto
Journal: Cancer Research (2007)

LB-106  Human epidermal growth factor receptor (EGFR) mutations are reported to trigger adenocarcinoma of the lung in transgenic mice, but further details regarding the carcinogenic process are needed. To investigate the role of EGFR and signal pathway in the lungs, we tried to generate transgenic mice with mouse EGFR mutation (L860R and delE748-A752) which corresponded to human EGFR mutation (L858R and delE746-A750), respectively. To express mouse EGFR mutation continuously only on the type II pneumocyte, we employed SPC promoter. Our transgenic line with EGFR mutation (delE748-A752) overexpressed EGFR mRNA and protein when compared to the control mice. Additionally, they produced multifocal adenocarcinoma of the lung at around 6 weeks of age and, without treatment, died of adenocarcinoma of the lung at around 16 weeks of age. Treatment with the EGFR tyrosine kinase inhibitor (TKI), gefitinib (5 mg/kg/day), or the EGFR and vascular endothelial growth factor receptor (VEGFR) TKI, vandetanib (5 mg/kg/day), markedly reduced phosphorylated EGFR to almost the same level as that of lung tissue in the control mice. The tumors disappeared within a week. The mice treated with gefitinib had a prolonged survival time of 30 weeks or more. The control mice have survived over one year without lung cancer. This model may be useful for developing improved therapies for lung cancer and investigating mechanisms of resistance to EGFR TKIs. This work is a collaborative effort with Dr. Jeffrey Whitsett, Cincinnati Children9s Hospital Medical Center.
Abstract 14792: Usefulness of Echocardiographic Parameters for Predicting Successful Weaning From Percutaneous Veno-arterial Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock or Cardiac Arrest
Authors: Kenichiro Sawada, Shoji Kawakami, Yoshio Tahara, Takahiro Nakashima, Toshiyuki Nagai, Tomoaki Kanaya, Yu Kataoka, Yasuhide Asaumi, Teruo Noguchi, Satoshi Yasuda
Journal: Circulation (2016)

Introduction: Recent studies show percutaneous veno-arterial extracorporeal membrane oxygenation (ECMO) is effective for surviving from cardiac arrest or cardiogenic shock. However, the proper prot...
Longitudinal Association of Amyloid Beta and Anxious-Depressive Symptoms in Cognitively Normal Older Adults
Authors: Nancy J. Donovan, Joseph J. Locascio, Gad A. Marshall, Jennifer Gatchel, Bernard J. Hanseeuw, Dorene M. Rentz, Keith A. Johnson, Reisa A. Sperling
Journal: American Journal of Psychiatry (2018)

Objective: To understand the role of depressive symptoms in preclinical Alzheimer’s disease, it is essential to define their temporal relationship to Alzheimer’s proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults. Method: A total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS). The authors evaluated continuous PiB binding as a predictor of GDS score or GDS cluster, calculated as total scores and mean scores for three GDS item clusters (apathy-anhedonia, dysphoria, and anxiety-concentration), across time (1–5 years; mean=3.8 years) in separate mixed-effects models with backward elimination. Initial predictors included PiB binding, age, sex, Hollingshead score, American National Adult Reading Test (AMNART) score, apolipoprotein E ε4 status, depression history, and their interactions with time. Results: Higher PiB binding predicted accelerated rates of increase in GDS score over time, adjusting for depression history. Higher PiB binding also predicted steeper rates of increase for anxiety-concentration scores, adjusting for depression history and the AMNART score-by-time interaction. In a post hoc model estimating anxiety scores without concentration disturbance items, the PiB binding-by-time interaction remained significant. Conclusions: Higher amyloid beta burden was associated with increasing anxious-depressive symptoms over time in cognitively normal older individuals. Prior depression history was related to higher but not worsening symptom ratings. These results suggest a direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and support the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer’s disease.
Role of Chromatin Damage and Chromatin Trapping of FACT in Mediating the Anticancer Cytotoxicity of DNA-Binding Small-Molecule Drugs
Authors: Elimelech Nesher, Alfiya Safina, Ieman Aljahdali, Scott Portwood, Eunice S. Wang, Igor Koman, Jianmin Wang, Katerina V. Gurova
Journal: Cancer Research (2018)

Abstract Precisely how DNA-targeting chemotherapeutic drugs trigger cancer cell death remains unclear, as it is difficult to separate direct DNA damage from other effects in cells. Recent work on curaxins, a class of small-molecule drugs with broad anticancer activity, shows that they interfere with histone–DNA interactions and destabilize nucleosomes without causing detectable DNA damage. Chromatin damage caused by curaxins is sensed by the histone chaperone FACT, which binds unfolded nucleosomes becoming trapped in chromatin. In this study, we investigated whether classical DNA-targeting chemotherapeutic drugs also similarly disturbed chromatin to cause chromatin trapping of FACT (c-trapping). Drugs that directly bound DNA induced both chromatin damage and c-trapping. However, chromatin damage occurred irrespective of direct DNA damage and was dependent on how a drug bound DNA, specifically, in the way it bound chromatinized DNA in cells. FACT was sensitive to a plethora of nucleosome perturbations induced by DNA-binding small molecules, including displacement of the linker histone, eviction of core histones, and accumulation of negative supercoiling. Strikingly, we found that the cytotoxicity of DNA-binding small molecules correlated with their ability to cause chromatin damage, not DNA damage. Our results suggest implications for the development of chromatin-damaging agents as selective anticancer drugs. Significance: These provocative results suggest that the anticancer efficacy of traditional DNA-targeting chemotherapeutic drugs may be based in large part on chromatin damage rather than direct DNA damage. Cancer Res; 78(6); 1431–43. ©2018 AACR.
Mechanobiologically optimized 3D titanium-mesh scaffolds enhance bone regeneration in critical segmental defects in sheep
Authors: Anne-Marie Pobloth, Sara Checa, Hajar Razi, Ansgar Petersen, James C. Weaver, Katharina Schmidt-Bleek, Markus Windolf, Andras Á. Tatai, Claudia P. Roth, Klaus-Dieter Schaser, Georg N. Duda, Philipp Schwabe
Journal: Science Translational Medicine (2018)

Three-dimensional (3D) titanium-mesh scaffolds offer many advantages over autologous bone grafting for the regeneration of challenging large segmental bone defects. Our study supports the hypothesis that endogenous bone defect regeneration can be promoted by mechanobiologically optimized Ti-mesh scaffolds. Using finite element techniques, two mechanically distinct Ti-mesh scaffolds were designed in a honeycomb-like configuration to minimize stress shielding while ensuring resistance against mechanical failure. Scaffold stiffness was altered through small changes in the strut diameter only. Honeycombs were aligned to form three differently oriented channels (axial, perpendicular, and tilted) to guide the bone regeneration process. The soft scaffold (0.84 GPa stiffness) and a 3.5-fold stiffer scaffold (2.88 GPa) were tested in a critical size bone defect model in vivo in sheep. To verify that local scaffold stiffness could enhance healing, defects were stabilized with either a common locking compression plate that allowed dynamic loading of the 4-cm defect or a rigid custom-made plate that mechanically shielded the defect. Lower stress shielding led to earlier defect bridging, increased endochondral bone formation, and advanced bony regeneration of the critical size defect. This study demonstrates that mechanobiological optimization of 3D additive manufactured Ti-mesh scaffolds can enhance bone regeneration in a translational large animal study.
Abstract 20127: Fluorescence-Activated Cell Sorting Confirms the Majority of Foam Cells in Human Coronary and Aortic Atherosclerosis Are Not Leukocyte-Derived
Authors: Sima Allahverdian, Ying Wang, Veronique Ollivier, Joshua A Dubland, Jean-Baptiste Michel, Michael A Seidman, Gordon A Francis
Journal: Circulation (2016)

Introduction: Smooth muscle cells (SMCs) comprise the majority of cells in human arterial intima, but their role in foam cell development and regression has received little attention compared to ma...
Final results of APG101_CD_002: APG101 plus reirradiation versus reirradiation in the treatment of patients with progressive glioblastoma.
Authors: Michael Platten, Harald Fricke, Klaus Junge, Grigory Kobyakov, Tobias Martens, Oliver Heese, Benedikt Wiestler, Maximilian G Schliesser, Andreas von Deimling, Josef Pichler, Elena Vetlova, Inga Harting, Juergen Debus, Christian Hartmann, Claudia Kunz, Martin Bendszus, Stephanie E. Combs, Wolfgang Wick
Journal: Journal of Clinical Oncology (2014)

2006^ Background: Preclinical data indicate antiinvasive activity of APG101, a CD95-ligand (CD95L)-binding fusion protein, and synergistic activity with radiotherapy in glioblastoma. In healthy volunteers, single doses of up to 20 mg/kg APG101 are safe. Methods: Patients (N=91) with progressive glioblastoma after standard radiochemotherapy (± 1 second-line chemotherapy), provided a tumour diameter of 1-4 cm and time since the end of radiotherapy ≥ 8 months, were randomised 1:2 stratified for tumour diameters ≤ or > 2.5 cm between radiotherapy (36 Gy; 5 times 2 Gy per week; rRT) or rRT+APG101 (400 mg weekly i.v.) to be continued until progression. CD95L was evaluated in tumour tissue. This open-label, non-comparative phase II trial (NCT01071837) sought to demonstrate a doubling in the 6-months progression-free survival (PFS-6) rate with rRT+APG101 assuming a 15% PFS-6 rate with rRT alone. The control arm with rRT alone was added to calibrate for the PFS-6 assumption. Results: Patient characteristics in the intention-to-treat population [N=84 (26 patients rRT, 58 patients rRT + APG101)] were balanced. The PFS-6 rates were 3.8% (95%-CI: 0.1 - 19.6) rRT and 20.7% (95%-CI: 11.2 - 33.4) for rRT+APG101 (p=0.04). Median PFS was 2.5 (95%-CI: 2.3-3.8) months and 4.5 (95%-CI: 3.7-5.4) months with a hazard ratio (HR) of 0.49 (95% CI: 0.27-0.88, p=0.0162). Cox regression analysis adjusted for tumour size revealed a HR for rRT+APG101 for death of any cause of 0.60 (95% CI: 0.36-1.01)] (p=0.0559). Patients with lower methylation levels at CpG2 in the CD95L promoter in the tumour tissue had a stronger risk reduction (HR=0.13 95% CI: 0.03-0.52) when treated with APG101. Conclusions: CD95 pathway inhibition in combination with rRT is an innovative concept with clinical efficacy. It warrants further clinical development. CD95L promoter methylation in the tumour may be developed as a biomarker. Clinical trial information: NCT01071837.
Reduction in mouse allergen exposure is associated with greater lung function growth in mouse sensitized and exposed children and adolescents with persistent asthma
Authors: Torie L. Grant, Wanda Phipatanakul, Matthew Perzanowski, Susan L. Balcer-Whaley, Roger Peng, Jean Curtin-Brosnan, Michelle Newman, Amparito Cunningham, Adnan Divjan, Mary Beth Bollinger, Robert A. Wise, Elizabeth C. Matsui
Journal: Journal of Allergy and Clinical Immunology (2018)
Response to: ‘Remission or low disease activity as a target in systemic lupus erythematosus’ by Ugarte-Gil<i>et al</i>
Authors: Margherita Zen, Andrea Doria
Journal: Annals of the Rheumatic Diseases (2018)

We appreciated the comments by Ugarte-Gil and co-authors1 on our report dealing with lupus low disease activity state (LLDAS) in Caucasian patients.2 

We agree that Caucasian patients with systemic lupus erythematosus (SLE) have a better prognosis compared with non-Caucasian ones, but, in our opinion, race does not fully elucidate the different results in terms of prevalence of low disease activity and remission obtained in the studies by Zen et al 2 and Ugarte-Gil et al .3 

The different design of the studies is more relevant than race in explaining the divergent results. Indeed, the Grupo Latino Americano De Estudio del Lupus (GLADEL) study3 analysed an inception cohort of patients shortly after the disease onset (median disease duration 0.3 years), and the authors assessed remission and low disease activity status (LDAS) during the first years of follow-up. …
Abstract 20638: Inhibition of HDAC6 Attenuates Chronic Angiotensin Ii-Induced Autophagy
Authors: Sheeja Rajasingh, Andras Czirok, Dona G Isai, Saheli Samanta, Thuy Cao, Lei Chen, Buddhadeb Dawn, Johnson Rajasingh
Journal: Circulation (2016)

Introduction: It has been shown that autophagy is playing one of the crucial cellular functions, which maintain the cellular homeostasis as well as cardiac hypertrophy, but the mechanism is poorly ...
Baicalein inhibits tumor migration and invasion by modulating cell adhesion and declining RhoA pathway in highly invasive non-small-cell lung cancer cells
Authors: Wan-Jiun Chen, Huei-Wen Chen, Sung-Liang Yu, Chong-Jen Yu, Yi-hsiu Juan, Jen-Yi Lee, Chao-Chi Ho, Hsuan-Yu Chen, Jeremy Chen, Chih-Hsin Yang, Pan-Chyr Yang
Journal: Cancer Research (2008)

4151  To inhibit metastasis, prolong survival, with an emphasis on restricting treatment-related toxicity are the key points in new drug development for anti-cancer therapy. Herein we reported that baicalein, a selective inhibitor of 12-lipoxygenase from Scutellariae Radix, significantly inhibited cancer cell migration (51.87% of inhibition) and invasion (50.6% of inhibition) concentration-dependently at sub-lethal concentration (≤5 microM) in the highly invasive human lung adenocacinoma cell line (CL1-5). Using the Affymetrix Human Genome U133 plus 2.0 Array, the baicalein-regulated gene expression patterns have been identified. The data showed that 2,423 genes were up-regulated by baicalein, whereas, 214 genes were down-regulated. These differentially expressed genes were further performed to the Complex Regulation Prediction Database (CRPD) for pathway enrichment analysis; the results showed that a cluster of the metastasis-related genes were highly regulated by baicalein. Real time quantitative RT-PCR confirmed that the cell adhesion molecules: integrin alphav (2.74 folds increased), alpha6 (3.46 folds increased), and beta1 (4.19 folds increased) were significantly up-regulated by baicalein. Immunostaining and flow cytometry also showed the induction of integrin alpha6 (1.55 folds increased), beta1 (2.8 folds increased) in protein levels on the baicalein-treated groups. Further studies demonstrated that the cell adhesion ability of CL1-5 cells to fibronectin was increased by baicalein (4.68 folds of induction at 5 microM) through inducing integrins expression. Pathway analysis also showed that baicalein exhibited the effects to down-regulate some cell motility related genes (keratin 19, cytokeratin II, CDC42 effector protein 1, 5, and Rac/cdc42 exchanger factor) and at least two cell invasion-related serine proteases (prss2, and prss3). Interestingly, the major regulators of the cell motility signaling pathway, RhoGTPase activating proteins (RhoGAPs), were up-regulated by baicalein, which might lead to reduce RhoA activation and inhibit translocation of cell body during cell migration process. In conclusion, these results suggested that baicalein could be a novel anti-cancer drug with the potential to inhibit cancer cell migration and invasion through up-regulating integrin alpha6beta1 expression to enhance cell adhesion and increasing RhoGAPs to inhibit the RhoA GTP pathway to reduce cell migration in the highly invasive lung adenocarcinoma cells.
Breath analysis for label-free characterisation of airways disease
Authors: Stephen J. Fowler
Journal: European Respiratory Journal (2018)

The appeal of exhaled breath gas as a potential source of novel respiratory biomarkers is clear. It provides an inexhaustible source of a medium that can be sampled noninvasively, and one that has been in direct contact with the organ of interest. Targeting volatile organic compounds (VOCs) allows us to see even deeper: these small molecules diffuse across barriers and hence breath sampling also captures VOCs from the pulmonary interstitium, the circulation and beyond. Whilst analytical chemists, engineers, and a few forward-thinking clinical researchers have been exploring the breath volatilome since the early 1970s, it is only in the last decade or so that clinical interest has really grown [1–6]. There are probably two main reasons for the slow speed of uptake. First, the medium is extremely complex, and the source of VOCs difficult to define. The air we breathe out contains VOCs from three main sources: the external environment (either inhaled or absorbed through the skin or via ingestion) [7, 8], and metabolism both human [9, 10] and non-human (the microbiome) [11, 12]. To further complicate matters these volatiles may interact, and may be themselves utilised in metabolic processes. The second challenge is common to all 'omics research: the lack of external validation needed to give confidence in findings and support clinical effectiveness studies. Potential breath volatile signatures emerge for key clinical characteristics and phenotypes in airways disease <http://ow.ly/7HzJ30hoCIJ>
Detection of EGFR gene mutations using the lavage fluid of CT-guided biopsy needle in NSCLC patients
Authors: Hiroki Otani, Shinichi Toyooka, Junichi Soh, Hiromasa Yamamoto, Hiroshi Suehisa, Naruyuki Kobayashi, Hideo Gobara, Katsuyuki Kiura, Susumu Kanazawa, Yoshihumi Sano, Hiroshi Date
Journal: Cancer Research (2008)

3668   EGFR mutations are exclusively present in NSCLC patients, especially in adenocarcinoma histology, never smoking status and female sex. Of clinical importance, EGFR mutations, exon19 deletion and exon21 point mutation at codon 858, were significantly associated with tumor response to EGFR-TKIs like gefitinib and erlotinib. We have previously developed the mutant-enriched PCR assay for EGFR exon19 deletion and L858R mutation and successfully detected EGFR mutation in small samples like CT guided biopsy samples and soluble DNAs from the pleural fluids. In this study, we examined whether epidermal growth factor receptor (EGFR) mutations was detectable in the lavage fluid of computed tomography (CT)-guided biopsy needle using PCR based assay. For 51 lung tumors diagnosed by CT guided biopsy, we extracted DNA from the lavage fluids of CT-guided lung biopsy needle. EGFR mutations, limited to exon19 deletions and exon21 L858R mutations, were examined using mutant-enriched PCR assay. We also examined EGFR mutation surgically resected corresponding 24 tumors to compare with results obtained by lavage fluids.  The amount of DNA obtained from lavage fluid of CT guided biopsy needle ranged from 0.7ng/µl to 47.2ng/µl. There was no significant difference in amount of extracted DNA according to characteristics of tumors including tumor size and GGO rate. Thirty-four of 51 lung tumor samples were histologically diagnosed as non-small-cell lung cancer (NSCLC). Exon19 deletions and exon21 L858R point mutations for EGFR were respectively detected in 4 (12%) and 13 (38%) of 34 NSCLC cases. EGFR mutation was significantly frequent in never-smoker among NSCLC cases. No mutation was found in other than NSCLC cases. EGFR mutation statuses in the 24 lavage fluids were consistent with those of corresponding surgical specimens available for 24 lung tumors.  Our results indicate that EGFR gene mutations were detectable in the lavage fluids of CT-guided biopsy needle. DNA genotype may be determined in extremely small clinical specimens using PCR based high sensitive assays.
Trends in Carotid Revascularization Procedures
Authors: Kosmas I. Paraskevas
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal