tbuckley/cabot-search huggingface dataset:
Panic Disorder
Authors: Wayne J. Katon
Journal: New England Journal of Medicine (2006)

A 30-year-old woman, recently divorced, presents with daily episodes of chest pain, shortness of breath, sweating, and palpitations. She feels very anxious when these episodes occur and worries about having a heart attack. She reports increasing avoidance of social activities, moodiness, poor sleep, and a low level of energy. She takes no medications and reports no drug or alcohol use. Her physical examination is normal. How should this case be managed?
Outcome of older patients with breast cancer with brain metastases.
Authors: J. Gachet, V. Girre, E. Brain, M. Falcou, P. H. Cottu, S. Piperno-Neumann, R. Le Scodan, L. Mignot
Journal: Journal of Clinical Oncology (2010)

e11501 Background: 60% of new cancers are diagnosed in patients aged 65 years and over. 20 to 40% of people treated for metastatic breast cancer will develop brain metastases. Methods: The aim of this retrospective study, performed in 2 French cancer centers, Institut Curie and Centre Rene Huguenin, was to describe clinical aspects of older breast cancer patients with brain metastases, discussing the various treatment options, their tolerance and efficacy in this specific population treated between 1998 and 2008. Results: Demographic data, tumor characteristics, metastatic sites and treatment of 95 patients were prospectively recorded. The median patient age was 70 years [65-87]. 19 patients (20%) were 75 years old or over. Median ECOG performans status was 2. 85 patients (89%) received radiotherapy. 5 major side effects required to stop the treatment (2 focal neurological deficiency and 3 deliriums). 58 patients (61.5%) received a systemic treatment. 6 chemotherapy treatments and 2 targeted therapies were stopped because of side effects. Hormonotherapy has been well tolerated. No toxic death occurred. The overall median survival was 4 months. Median survival of patients who did not receive any treatment was 1 month versus 5 months when at least one treatment was given (p<0.004). Median survival was 5 months with radiotherapy versus 1 month without (p<0.004), 9 months with chemotherapy versus 2 months without (p<0.0001) and 8 months with hormonotherapy versus 3 months without (p<0.0009). Unfortunately, no geriatric data were available because of some patients were treated ten years ago. Only 2 patients wished not to be treated. Conclusions: The different treatments received appear safe. Median survival in older patients with breast cancer treated for brain metastases is comparable as median survival described in studies including young patients. Despite their age, patients wish to receive a treatment and are susceptible to benefit from it. No significant financial relationships to disclose.
α-Ketoglutarate Accelerates the Initial Differentiation of Primed Human Pluripotent Stem Cells
Authors: Tara TeSlaa, Andrea C. Chaikovsky, Inna Lipchina, Sandra L. Escobar, Konrad Hochedlinger, Jing Huang, Thomas G. Graeber, Daniel Braas, Michael A. Teitell
Journal: Cell Metabolism (2016)
Adjuvant radiotherapy versus wait-and-see strategy for pathologic T3 or margin-positive prostate cancer: A meta-analysis.
Authors: Mohammad Parvez Shaikh, Matthew M. Harkenrider, Meng-Jia Wu
Journal: Journal of Clinical Oncology (2015)

19 Background: Optimal management after radical prostatectomy (RP) remains controversial in patients with pathologic T3 or margin-positive prostate cancer with the options being early adjuvant radiotherapy (ART) versus wait-and-see (WS). Methods: A comprehensive Medline search to identify randomized controlled trial (RCT) of ART vs WS was done. Synthesized results from the included studies show Metastasis-Free Survival (MFS) and overall survival (OS) rates at 10 years as well as Grade 2 or greater GI and GU toxicities in the studies. Results were based on the random-effect (RE) model if there was evidence of between-trial heterogeneity, otherwise the fixed-effect (FE) model was used. Results: A total of 3 RCTs (ARO9602/AUO AP09/95, EORTC22911, SWOG8794) were identified with 1,737 patients (ART: n=864, WS: n=873). 10-year estimates of MFS and OS rates were reported for SWOG and EORTC studies, and estimated for ARO 96-02/AUO AP09/95 study from their Kaplan-Meier curves (Table). Pooled 10-year MFS data showed a significant improvement with ART vs WS (OR= 0.77; 95% CI 0.62–0.96, p=0.02, FE). However, pooled 10-year OS was not significantly different (OR= 0.98; 95% CI 0.64–1.49, p=0.91, RE). Grade 2 or greater GI toxicity was reported by all three studies and was significantly higher in ART (2.5%) compared with WS (1.1%), p=0.04. Grade 2 or greater GU toxicity was reported by ARO9602 and EORTC studies and was significantly higher in ART (17.1%) compared with WS (10.3%), p=0.0004. Conclusions: 10-year MFS is significantly improved with ART compared with WS. No benefit in 10-year OS was found. Grade 2 or greater GI and GU toxicities where greater in ART compared with WS. [Table: see text]
Comparative <i>in vitro</i> properties and pharmacokinetics of paclitaxel following the administration of Taxol and Paxene
Authors: C. D. Scripture, J. Szebeni, W. D. Figg, A. Sparreboom
Journal: Journal of Clinical Oncology (2005)

2090 Background: Taxol is a formulation of paclitaxel containing a mixture of Cremophor EL-P (CrEL-P) and ethanol. Paxene is similar to Taxol, except for the use of unpurified Cremophor EL (CrEL) and the addition of a small amount of citric acid to increase drug stability. Here, we investigated whether any altered physicochemical properties of the formulation changes paclitaxel pharmacokinetics. Methods: The size and modality of distribution of CrEL-P and CrEL micelles was determined by dynamic-light scattering. The effect of vehicle composition on the fraction unbound paclitaxel in vitro was determined by equilibrium dialysis using a [14C]paclitaxel tracer. Paclitaxel pharmacokinetics was studied in cancer patients receiving 3-h infusions of Taxol (61 patients) or Paxene (26 patients) at 100, 135, 175, or 200 mg/m2. Comparative pharmacokinetics of CrEL-P and CrEL were obtained in 14 and 6 patients, respectively, using noncompartmental analysis. Results: On average, the size of micelles present in Taxol was slightly smaller (9 to 13%) than those present in Paxene. The surface tension and critical micellar concentration were also similar for the two formulations, with mean values of 37.0 and 38.1 mN/m and 0.0387 and 0.0307 mg/mL, respectively. The fraction unbound paclitaxel in the presence of CrEL-P/ethanol or CrEL/citric acid/ethanol was not significantly different at identical excipient concentrations (P > 0.05). Over the tested dose range, the mean clearance of paclitaxel decreased from 45.1 to 16.9 L/h for Taxol, and from 50.7 to 16.4 L/h for Paxene. Paclitaxel pharmacokinetics was not significantly different for Taxol and Paxene (P > .37), suggesting that the respective excipients modulate the systemic clearance of paclitaxel to a similar extent. Concentrations of the excipient following the administration of CrEL-P or CrEL were also in the same range. Conclusions: The difference in formulation between Taxol and Paxene does not affect micelle formation, and does not affect quantitative aspects of the vehicle-paclitaxel interaction in vitro and in vivo. No significant financial relationships to disclose.
Stability through variability: Homeostatic plasticity and psychological resilience
Authors: Dennis J. L. G. Schutter, Miles Wischnewski, Harold Bekkering
Journal: Behavioral and Brain Sciences (2015)

Abstract According to Kalisch et al., adopting a cognitive positive appraisal style promotes internal bodily homeostasis and acts as a safeguard against the detrimental effects of stress. Here we will discuss results from recent noninvasive brain stimulation studies in humans to illustrate that homeostatic plasticity provides a neural mechanistic account for the positive appraisal style theory of resilience.
Once-daily tiotropium Respimat (R) as add-on to at least medium- to high-dose ICS, with or without LABA, improves lung function in patients with symptomatic asthma, independent of allergic status
Authors: R. Dahl, E. D. Bateman, T. Casale, E. Pizzichini, M. Vandewalker, J. C. Virchow, M. Engel, R. Sigmund, P. Moroni-Zentgraf, H. A. M. Kerstjens
Journal: Allergy (2014)
Peripherally Inserted Central Catheters—Improving Appropriateness With a Dedicated and Rigorous Team
Authors: Patrizia Mordenti, Francesco Oleari, Luigi Cavanna
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
Abstract CT127: Results from a phase II clinical study in Chinese population: treatment with Chinese medicine cocktail LQ for patients with stage IIIB/IV advanced non-small cell lung cancer
Authors: Lei Zhang, Chengyu Wu
Journal: Cancer Research (2016)

Abstract OBJECTIVES: To estimate the response of Chinese medicine “cocktail” LQ in patients with advanced non-small cells lung cancer, a phase II multicenter, double-blind, randomized clinical trial was conducted. Patients with IIIB/IV stage received LQ and natural product control Spirulina. The end points for this study included overall survival (OS), progression free survival (PFS), safety of the regimen, disease control rate (DCR) and other criteria. METHODS: Patients with stage IIIB/IV advanced NSCLC cancer received LQ treatment and Spirulina. Toxicity was assessed. Quality of life was assessed. The primary objective was overall survival. RESULTS: A hundred and twenty patients were enrolled and 80 were treated. Median age was 60 years (range, 42-75). The median overall survival rate in LQ group and Spirulina group is 10.9 months vs 7.4 months respectively (p&amp;lt;0.0001). Median progression survival free survival is 3.84 months vs 1.97 months in LQ and Spirulina group (p&amp;lt;0.01). There is no side effect were found in there. There were 42 patients with stable disease with the disease control rate of 59.15% in LQ treatment group, Compare with Spirulina group, there were only 4 standard disease, for disease control rate of 11.76% (p&amp;lt;0.001). There are no notable toxicities were found in LQ treatment group. CONCLUSIONS: This first-in-human phase II study of Chinese medicine cocktail LQ used as first-line therapy in patients with advanced NSCLC. LQ, a promising new drug, provides a safer and high effective therapy for late-stage lung cancer patients. Citation Format: Lei Zhang, Chengyu Wu. Results from a phase II clinical study in Chinese population: treatment with Chinese medicine cocktail LQ for patients with stage IIIB/IV advanced non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT127.
Abstract 1378: Generating quality control reference standards to evaluate ultrasensitive variant detection
Authors: Marija Debeljak, Lisa Haley, Derek A. Anderson, Emily M. Adams, Masaya Suenaga, Katie Beierl, Ming-Tseh Lin, Michael Goggins, Christopher D. Gocke, James R. Eshleman
Journal: Cancer Research (2016)

Abstract Introduction: Ultrasensitive point mutation detection can facilitate minimal residual disease detection, early detection of cancer, and therapeutic monitoring of cancer patients. However, nearly identical mutant and wildtype molecules exhibit crosstalk with most technologies, thus producing high background levels. To evaluate technologies against each other for accurate ultrasensitive point mutation detection it is crucial to supply laboratories with reference samples of various dilutions. Methods: We tested a series of sample mixes with digital-droplet PCR and next generation sequencing. Using linearity and accuracy as the gold standard, we empirically introduced two corrections to generate improved quality control reagents. Baseline variant allele frequency (VAF) in the parental cell line was used to correct for copy number variation of variant, while haplotype counting was used to correct technical errors (cell counting and pipetting). Results: Correlation between the level of dilution and the measured VAF was relatively good (R2 = 0.80) when measured using ddPCR. However, correcting for the parental VAFs substantially improved the correlation (R2 = 0.97). In contrast, correlation of the cell count dilution and the measured VAF, as determined by next generation sequencing (AmpliSeq), was initially relatively poor (R2 = 0.63). However, substantial improvement in correlation was achieved by correcting for the parental VAFs (R2 = 0.94). In addition, correcting by haplotype counting alone only slightly improved accuracy in both technologies (ddPCR, from R2 = 0.80 to R2 = 0.81; AmpliSeq, from R2 = 0.63 to R2 = 0.64). Furthermore, correcting for both factors resulted in the best correlation for ddPCR-generated data (R2 = 0.99); however, introducing both corrections for AmpliSeq data did not prove more beneficial than correcting for parental VAFs alone (both corrections, R2 = 0.94 compared to parental VAF correction only, R2 = 0.94). Conclusions: Validation of ultrasensitive variant detection requires standardized reference samples. These will also permit assessing various ultrasensitive detection technologies against one another. Citation Format: Marija Debeljak, Lisa Haley, Derek A. Anderson, Emily M. Adams, Masaya Suenaga, Katie Beierl, Ming-Tseh Lin, Michael Goggins, Christopher D. Gocke, James R. Eshleman. Generating quality control reference standards to evaluate ultrasensitive variant detection. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1378.
Abstract 4442: Very low methylation is a novel epigenetic regulatory mechanism in normal tissues and predisposes to hypermethylation in cancer
Authors: priyanka madireddi, Jaroslav Jelinek, Justin Lee, Takahiro Sato, Jean-Pierre Issa
Journal: Cancer Research (2016)

Abstract High level DNA methylation of promoter CpG Island (CGI) represses gene expression. However, low-level CGI methylation is usually not distinguished from complete absence of methylation. Here we show that Very Low Methylated Regions (VLMRs 1-20%) on promoter CGIs are present in up to 20% of human and mouse genes and negatively correlate with gene expression in all tissues examined. In vitro, low-level methylation directly represses reporter gene expression; an effect mediated by methyl-CpG-binding proteins as transient knockdown of MBD4 reverses this repression. In vivo VLMR genes are enriched for polycomb occupancy but can also occur in H3K4me3 occupied promoters, where it correlates with gene repression independent of polycomb complex binding. VLMRs in promoter CGIs in healthy WBCs are 19 fold and 65 fold more likely to gain hypermethylation in Acute Myelogenous Leukemia and Myelodysplastic Syndrome patients respectively compared to unmethylated CGIs (&amp;lt;1%). Our study reveals a novel epigenetic control mechanism that has strong effects on gene expression in normal tissues and accounts for most of the gene specificity of hypermethylation in cancer. Citation Format: priyanka madireddi, Jaroslav Jelinek, Justin Lee, Takahiro Sato, Jean-Pierre Issa. Very low methylation is a novel epigenetic regulatory mechanism in normal tissues and predisposes to hypermethylation in cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4442.
The fate of medications evaluated for ischemic stroke pharmacotherapy over the period 1995–2015
Authors: Xiaoling Chen, Kewei Wang
Journal: Acta Pharmaceutica Sinica B (2016)

Stroke is a brain damage caused by a loss of blood supply to a portion of the brain, which requires prompt and effective treatment. The current pharmacotherapy for ischemic stroke primarily relies on thrombolysis using recombinant tissue plasminogen activators (rt-PAs) to breakdown blood clots. Neuroprotective agents that inhibit excitatory neurotransmitters are also used to treat ischemic stroke but have failed to translate into clinical benefits. This poses a major challenge in biomedical research to understand what causes the progressive brain cell death after stroke and how to develop an effective pharmacotherapy for stroke. This brief review analyzes the fate of about 430 potentially useful stroke medications over the period 1995–2015 and describes in detail those that successfully reached the market. Hopefully, the information from this analysis will shed light on how future stroke research can improve stroke drug discovery.
Radioimmunotherapy with 90Y-Ibritumomab Tiuxetan (Zevalin®) as Consolidation of First Remission in Patients with Advanced Stage Follicular Lymphoma: A ’Real-Time’ MBR RQ-PCR Analysis.
Authors: Lindsey Goff, Karin Summers, Sameena Iqbal, Jens Kuhlmann, Michael Kunz, Anton Hagenbeek, Andrew Lister, Ama Rohatiner
Journal: Blood (2007)
Abstract 4999: Cellular mechanism of action of bispecific T-cell engager (BiTE®) antibody constructs targeting Folate Receptor 1
Authors: Julie M. Bailis, Jessica N. Orf, Alexander Sternjak, Brian Belmontes, Ryan Case, Natalia Grinberg, Wesley Chang, Beth Hinkle, Matthias Friedrich
Journal: Cancer Research (2016)

Abstract Bispecific T-cell engaging (BiTE®) antibody constructs connect T cells to target-positive cells to induce cytotoxicity. Clinical proof of concept was achieved in B cell malignancies with the anti-CD19 BiTE® Blincyto®, and several BiTE® antibody constructs are currently in development for solid tumor indications. With the goal of developing a BiTE® for ovarian cancer, we focused on targeting the Folate Receptor (FOLR1). FOLR1 mRNA and protein are highly expressed in &amp;gt;80% of ovarian tumor samples. The FOLR1 protein localizes to the cell membrane of ovarian tumor epithelial cells, whereas in normal tissues such as kidney tubules expression is restricted to the apical cell layer. We generated human FOLR1-BITE® antibody constructs that cross react to cynomolgus monkey and here present the preclinical characterization of these molecules. FOLR1-BiTE® antibody constructs had low nanomolar binding affinity for FOLR1 but did not bind to other FOLR family members. The FOLR1-BiTE® antibody constructs recognized diverse epitopes of the FOLR1 protein. In vitro, binding of FOLR1-BiTE® to CD3 on T cells and FOLR1 on tumor cells led to upregulation of CD25, CD69 and GITR on T cells, as well as release of cytokines including TNF, IFNγ, IL-6 and MCP-1. T cell activation by FOLR1-BiTE® was strictly target cell-dependent. Using time lapse imaging, we demonstrated that T cells were recruited to cancer cells expressing FOLR1 to form a cytolytic synapse and induce target cell lysis. Cytotoxicity mediated by FOLR1-BiTE® antibody constructs occurred even at very low target expression levels (1000 receptors per cell), and was not impacted by the presence of soluble receptor at levels found in ovarian cancer patients. FOLR1-BiTE® antibody constructs also mediated redirected lysis of cell lines that were resistant to standard of care chemotherapy. The in vivo activity of the FOLR1-BiTE® was explored in mouse xenograft studies where immunocompromised mice were implanted with mixtures of human T cells and human cancer cell lines. Daily intraperitoneal administration of the BiTE® inhibited tumor growth, even though the serum half-life of the BiTE® was just a few hours. Citation Format: Julie M. Bailis, Jessica N. Orf, Alexander Sternjak, Brian Belmontes, Ryan Case, Natalia Grinberg, Wesley Chang, Beth Hinkle, Matthias Friedrich. Cellular mechanism of action of bispecific T-cell engager (BiTE®) antibody constructs targeting Folate Receptor 1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4999.
Neoadjuvant dose-dense gemcitabine and cisplatin (DDGC) in patients (pts) with muscle-invasive bladder cancer (MIBC): Final results of a multicenter phase II study.
Authors: Elizabeth R. Plimack, Jean H. Hoffman-Censits, Alexander Kutikov, Richard E. Greenberg, Marijo Bilusic, David Y. T. Chen, Rosalia Viterbo, Costas D. Lallas, Jianqing Lin, Edouard John Trabulsi, Daniel M. Geynisman, William Kevin Kelly, Marc C. Smaldone, Karthik Devarajan, Beth Adaire-Halenda, Charlotte Cione, Deborah Kilpatrick, Gail Duncan, Yu-Ning Wong
Journal: Journal of Clinical Oncology (2014)

4513 Background: Neoadjuvant cisplatin (cis) based chemotherapy prior to radical cystectomy (RC) is standard of care for localized MIBC. Combination gemcitabine (gem) and cis is frequently used, but has not been tested prospectively. We sought to evaluate the activity of this combination when given in a dose dense fashion. Methods: Pts with MIBC, cT2-T4a, cN0-N1 with CrCl >=50 were eligible. Pts received 3 cycles of DDGC (gem 1200 mg/m2, cis 70mg/m2) on day 1, with pegfilgrastim 6 mg day 2 or 3, every 2 wks. Pts with CrCl 50-60 could receive cis split over 2 days. RC with lymph node dissection was to be performed 4-8 weeks after the last dose of DDGC. Primary endpoint was pathologic complete response (pT0) rate. Results: 32 pts were enrolled at 2 institutions (FCCC, TJU) over 14 months. One withdrew consent prior to receipt of DDGC. Among the 31 evaluable pts, median age was 69 (range 51 – 82). Baseline clinical stage was T2N0M0 (11), T3N0M0 (15), T4aN0M0/TxN1M0 (5). 25 pts received all 3 cycles of DDGC, with 1/25 requiring dose reduction of gem for thrombocytopenia. 6 discontinued DDGC early due to gr 3/4 vascular (3), gr 2/3 renal (2), or gr 3 hematologic (1) toxicity. Analysis of toxicities among the first 13 pts revealed 2 pts with MI (1 in cycle 1 (C1) with resulting CHF precluding surgery, 1 D#3 post-op) and 2 pts with VTE (1 PE in C2, 1 DVT D#15 post-op), and 1 pt who required CABG between DDGC and RC. The protocol was then amended to require cardiac clearance prior to study entry. Despite this, further vascular toxicity was seen with 1 DVT in C3 and 1 CVA in C1. The study was thus closed prior to target accrual of 44 pts. 30/31 pts underwent RC, 28 within 8 weeks of last DDGC. Median time from start of DDGC to RC was 9.3 weeks (range 5-29). 10/31 pts had pT0 (32%, 95% CI 16-48%). An additional 4 (13%) were downstaged to non-muscle invasive disease. Median f/up is 36 wks. 4 pts have recurred. 5 pts have died, 2 due to metastases. Conclusions: DDGC yielded pT0 rates similar to those reported with Accelerated MVAC. However significant vascular toxicity precluding, delaying or increasing the risk of surgery was noted, leading to early study closure. Clinical trial information: NCT01611662.