tbuckley/cabot-search huggingface dataset:
Phase II trial of pemetrexed (P) and bevacizumab (B) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC): An interim analysis
Authors: M. V. Karamouzis, D. Friedland, R. Johnson, K. Rajasenan, B. Branstetter, A. Argiris
Journal: Journal of Clinical Oncology (2007)

6049 Background: P is a multi-targeted antifolate with single-agent activity in recurrent or metastatic HNSCC (RR 26%, Pivot et al. Br J Cancer 2001;85:649–55) and a preferable toxicity profile compared with cisplatin or the taxanes. B is a monoclonal antibody against the vascular endothelial growth factor that has been successfully incorporated in the treatment of other advanced solid tumors. Methods: Eligible pts had pathologically documented HNSCC, ECOG performance status 0–1, measurable disease, no history of bleeding diathesis or hemoptysis, and were not on anticoagulation. Pts had no prior systemic therapy for recurrent or metastatic HNSCC; chemotherapy as part of initial potentially curative therapy, but without P or B, was allowed if completed &gt;6 months earlier. Treatment consisted of P 500 mg/m 2 and B 15 mg/Kg, both given intravenously every 21 days, until disease progression or intolerable toxicity. All patients received folic acid, vitamin B12, and corticosteroid prophylaxis. The primary endpoint was the time to progression (TTP) with a sample size of 40 pts (one stage design) with planned interim safety analysis after the first 6 and 12 pts. Results: 14 pts have been enrolled. Median age 64 years (35–84); male/female 13/1; PS 0/1: 7/7; prior chemotherapy: 8; primary site: oropharynx (7), larynx (4), oral cavity (3). Median number of cycles 5 (1–10). With a median follow up of 5.5 months, median TTP was 6 months (95% CI, 4–8). 11 pts were evaluable for response using RECIST. Best response was CR: 2, PR: 3, SD: 6, PD: 0, with ORR 45%. There were no grade 4 toxicities in 14 evaluable pts; 2 pts had grade 3 hemorrhagic events in the first cycle (1 tumor-related and 1 due to gastric ulcer post gastrostomy tube placement), and both discontinued treatment. 3 other pts had grade 1–2 hemorrhagic events. The relationship of these events to treatment was difficult to ascertain. Other grade 3 toxicities were stomatitis, dysphagia, and fatigue (all occurred in 1 pt). Conclusions: Preliminary results show that P plus B is a novel, highly active regimen that may represent a new treatment paradigm in HNSCC. However, bleeding complications were frequent in pts with susceptibility to such events. Study accrual continues. No significant financial relationships to disclose.
Dynamics of IFN-β Responses during Respiratory Viral Infection. Insights for Therapeutic Strategies
Authors: Alastair Watson, C. Mirella Spalluto, Christopher McCrae, Doriana Cellura, Hannah Burke, Danen Cunoosamy, Anna Freeman, Alex Hicks, Michael Hühn, Kristoffer Ostridge, Karl J. Staples, Outi Vaarala, Tom Wilkinson
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Viral infections are major drivers of exacerbations and clinical burden in patients with asthma and chronic obstructive pulmonary disease (COPD). IFN-β is a key component of the innate immune response to viral infection. To date, studies of inhaled IFN-β treatment have not demonstrated a significant effect on asthma exacerbations.Objectives: The dynamics of exogenous IFN-β activity were investigated to inform on future clinical indications for this potential antiviral therapy.Methods: Monocyte-derived macrophages (MDMs), alveolar macrophages, and primary bronchial epithelial cells (PBECs) were isolated from healthy control subjects and patients with COPD and infected with influenza virus either prior to or after IFN-β stimulation. Infection levels were measured by the percentage of nucleoprotein 1-positive cells using flow cytometry. Viral RNA shedding and IFN-stimulated gene expression were measured by quantitative PCR. Production of inflammatory cytokines was measured using MSD.Measurements and Main Results: Adding IFN-β to MDMs, alveolar macrophages, and PBECs prior to, but not after, infection reduced the percentage of nucleoprotein 1-positive cells by 85, 56, and 66%, respectively (P < 0.05). Inhibition of infection lasted for 24 hours after removal of IFN-β and was maintained albeit reduced up to 1 week in MDMs and 72 hours in PBECs; this was similar between healthy control subjects and patients with COPD. IFN-β did not induce inflammatory cytokine production by MDMs or PBECs but reduced influenza-induced IL-1β production by PBECs.Conclusions:In vitro modeling of IFN-β dynamics highlights the potential for intermittent prophylactic doses of exogenous IFN-β to modulate viral infection. This provides important insights to aid the future design of clinical trials of IFN-β in asthma and COPD.
The harms to health caused by aviation noise require urgent action
Authors: Jangu Banatvala, Martin Peachey, Thomas Münzel
Journal: BMJ (2019)

In 1905, the Nobel prize winning bacteriologist Robert Koch wrote, “The day will come when man will have to fight noise as inexorably as cholera and the plague.”

Koch was before his time and could not have anticipated the rapid growth of aviation and the impact that aviation noise would have on health. In October 2018, the World Health Organization published its new guidelines for environmental noise.1 The guidelines make source specific recommendations for noise from aviation, as well as road, rail, wind turbines, and leisure. They include tough new lower thresholds, reflecting the growing body of evidence about the harmful effects of noise on health.

This matter is not new. In 1999, in an attempt to achieve a balance between health hazards for communities near airports and current and proposed developments, the WHO Charter on Transport and Environmental Health recommended that health of the community should be put first when considering transport since adverse environmental effects fall disproportionately on the vulnerable, particularly children; the infirm; and older people.2 It also recommended the “polluter pays” principle—the commonly …
Practical Gynecology. A Comprehensive Text-Book for Students and Physicians.
Journal: JAMA (1903)

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
AB0001 T-cell immunity in hla-b27+ and hla-b27- patients with reactive arthritis (rea) of different aetiology
Authors: MB Dzhus, VV Chopyak
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Estimation of T-cell immunity pacularities in HLA B27+ and HLA B27- patients with reactive arthritis (ReA) of different aetiology. <h3>Methods</h3> We observed 67 pts with ReA: male -62 pts., female 5 pts., mean age 27 ± 3, 2 yrs., men duration of illness 24 ± 6 months. In all patients triggering infections were detected: in 36 pts. high levels of chlamydia trachomatis IgG and IgM together with HSV I IgG and IgM were observed, in 16 pts.-serological activation of enterobacterial infection and in 10 pts. triggering agent was not found. Specific monoclonal antibodies were used to detect CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup>, CD16<sup>+</sup>, CD19<sup>+</sup>, CD22<sup>+</sup> and presence of HLA-B27 antigen. <h3>Results</h3> It was estimated that all patients with chlamidial infection were HLA-B27 positive. This pts had higher levels of CD4<sup>+</sup> (p &lt; 0,001), CD3<sup>+</sup> (p &lt; 0,01), CD22<sup>+</sup> (p &lt; 0,01), CD19<sup>+</sup> (p &lt; 0,001) and encreased level og IgG (p &lt; 0,001) and CIC (p &lt; 0,01) in comparison to HLA-B27 negative pts. Presence of HLA-B27 correlated with duration and activity of ReA. <h3>Conclusion</h3> Chlamidial infection often associates with presence of HLA-B27 antigen. This pts. have more expressed changes in T-cell immunity that leads to the longer duration and severe activity of the disease.
International Clinics. A Quarterly of Clinical Lectures.
Journal: JAMA (1898)

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
Successful generation of patient-derived xenografts and cell lines as preclinical models for sarcomas.
Authors: Tadashi Kondo, Rieko Oyama, Fusako Kito, Rei Noguchi, Emi Hattori, Mami Takahashi, Hitoshi Ichikawa, Akihiko Yoshida, Akira Kawai
Journal: Journal of Clinical Oncology (2019)

e22549 Background: The establishment of patient-derived preclinical models has been a challenge issue in sarcomas, because of the rarity of diseases. We report our successful experience in establishing patient-derived sarcoma xenografts and cell lines. Methods: Tumor tissue samples from sarcoma patients undergoing surgery were collected by a team of orthopedicians and pathologists. Small tumor fragments were subcutaneously transplanted to immunodeficient NOG mice. The other part was used to establish a cell line using serum-containing media. The omics profiling was performed to examine the preservation of molecular backgrounds during the model establishment. Effects of FDA-approved drugs were examined in the established models. Results: Since April 2014, tumor samples from 246 sarcoma cases have been processed. The sample characteristics are summarized in the table. Currently we have established PDXs and cell lines from 39 and 27 cases, respectively. Xenografts and cell lines were established from unique sarcomas such as CIC-DUX4 fusion positive sarcoma, extraskeletal osteosarcoma, primary leiomyosarcoma of bone, and alveolar soft part sarcoma. A take rate of xenografts and cell lines varied among the sarcoma types. Omics profiles considerably changed during the process of model establishment. Anti-cancer drugs with significant tumor suppressive effects were detected. Conclusions: Our patient-derived cancer models will facilitate translational sarcoma research. The original biological features preserved in the xenografts and cell lines should be clarified to optimize the utility of sarcoma models. Currently, our cell lines are available for the academic researchers upon a request.
ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions
Authors: Arnaud Bourdin, L. Bjermer, C. Brightling, G. Brusselle, P. Chanez, F. Chung, A. Custovic, Z. Diamant, S. Diver, R. Djukanovic, D. Hamerlijnck, Ildikó Horváth, S. Johnston, F. Kanniess, N. Papadopoulos, A. Papi, R. Russell, D. Ryan, K. Samitas, T. Thomy, E. Zervas, M. Gaga
Journal: European Respiratory Journal (2019)

Despite the use of effective medications to control asthma, severe exacerbations in asthma are still a major health risk and require urgent action on the part of the patient and physician to prevent serious outcomes such as hospitalisation or death. Moreover, severe exacerbations are associated with substantial healthcare costs and psychological burden, including anxiety and fear for patients and their families. The European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS) set up a task force to search for a clear definition of severe exacerbations, and to also define research questions and priorities. The statement includes comments from patients who were members of the task force.
Adjuvant radiation therapy in node-positive vulvar cancer.
Authors: Eric Xanthopoulos, Surbhi Grover, Michael Nino Corradetti, Margaret Mangaali, Marina Heskel, Lilie Lin
Journal: Journal of Clinical Oncology (2013)

5609 Background: Adjuvant radiation (RT) has been demonstrated to improve overall survival (OS) in vulvar cancer patients with 2+ positive lymph nodes, but its role in patients with one positive lymph node is uncertain. We report on the largest and longest study of survival in patients with and without radiation following surgery in patients with vulvar cancer. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified node-positive women with squamous cell carcinoma of the vulva treated with and without external beam radiation following surgery. The Kaplan-Meier approach, log-rank tests and Cox modeling assessed OS. Results: All results are listed as women without vs with adjuvant radiation. From 1988 – 2008, 420 patients received surgery alone vs 753 women who received adjuvant radiation. Patient characteristics were well balanced across cohorts, including tumors ≤ or &gt; than 2 cm (p = 0.31), grade (p = 0.41), marital status (p = 0.20), provider type (p = 0.49), and AJCC stage (p = 0.35). Both groups also had similar incidence of biopsy of any kind (p = 0.40), lymph node dissection (p = 0.77), median number of nodes excised (p = 0.12), and type of surgery (p = 0.49). Median age (75 vs 70 y, p &lt;0.01) and race (94% vs 89% white, p = 0.01) were adjusted using Cox regression. Median survivor follow-up was 45 m (range 0 - 236 m). Adjuvant radiation was associated with survival across all node-positive patients (22 vs 29 m, p &lt;0.01), as well as in the subset of women with just one positive lymph node (37 vs 70 m, p &lt;0.01) or 2+ positive lymph nodes (14 vs 18 m, p &lt;0.01). On multivariable Cox regression, adjuvant radiation (95% CI 0.85 - 0.96), diameter (CI 1.28 - 2.01), marital status (CI 0.65 - 0.93), the number of positive nodes (CI 1.06 - 1.11), and the ratio of positive-to-excised nodes (CI 1.61 - 2.98) were all associated with survival (p &lt;0.01 for each). Conclusions: The largest cohort study of node-positive squamous cell carcinoma of the vulva suggests adjuvant radiation is associated with OS.Studies have reported that adjuvant radiation may provide a survival benefit in women with 2+ positive lymph nodes. Our findings suggest patients with one positive lymph node also may benefit from adjuvant radiation.
Pathogenic Germline Variants in Patients With Metastatic Breast Cancer
Authors: Kelsey Stuttgen, Sarah Croessmann, John Fetting, Vered Stearns, Raquel Nunes, Roisin M. Connolly, Ben Ho Park
Journal: JAMA Oncology (2019)

Detection of Pathogenic Variants With Germline Genetic Testing in Patients With Prostate Cancer and Melanoma
Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer’s disease
Authors: Michael Ewers, Nicolai Franzmeier, Marc Suárez-Calvet, Estrella Morenas-Rodriguez, Miguel Angel Araque Caballero, Gernot Kleinberger, Laura Piccio, Carlos Cruchaga, Yuetiva Deming, Martin Dichgans, John Q. Trojanowski, Leslie M. Shaw, Michael W. Weiner, Christian Haass
Journal: Science Translational Medicine (2019)

Higher CSF sTREM2 concentrations are associated with slower rates of cognitive decline in subjects with Alzheimer’s disease.
An anti-CRF antibody suppresses the HPA axis and reverses stress-induced phenotypes
Authors: Hunter S. Futch, Karen N. McFarland, Brenda D. Moore, M. Zino Kuhn, Benoit I. Giasson, Thomas B. Ladd, Karen A. Scott, Melanie R. Shapiro, Rachel L. Nosacka, Marshall S. Goodwin, Yong Ran, Pedro E. Cruz, Daniel H. Ryu, Cara L. Croft, Yona Levites, Christopher Janus, Paramita Chakrabarty, Andrew R. Judge, Todd M. Brusko, Annette D. de Kloet, Eric G. Krause, Todd E. Golde
Journal: The Journal of Experimental Medicine (2019)

Hypothalamic–pituitary–adrenal (HPA) axis dysfunction contributes to numerous human diseases and disorders. We developed a high-affinity monoclonal antibody, CTRND05, targeting corticotropin-releasing factor (CRF). In mice, CTRND05 blocks stress-induced corticosterone increases, counteracts effects of chronic variable stress, and induces other phenotypes consistent with suppression of the HPA axis. CTRND05 induces skeletal muscle hypertrophy and increases lean body mass, effects not previously reported with small-molecule HPA-targeting pharmacologic agents. Multiorgan transcriptomics demonstrates broad HPA axis target engagement through altering levels of known HPA-responsive transcripts such as Fkbp5 and Myostatin and reveals novel HPA-responsive pathways such as the Apelin-Apelin receptor system. These studies demonstrate the therapeutic potential of CTRND05 as a suppressor of the HPA axis and serve as an exemplar of a potentially broader approach to target neuropeptides with immunotherapies, as both pharmacologic tools and novel therapeutics.
Induced fluorescence of medullary carcinoma of the thyroid: A technology with potential to improve visualization of malignant tissue at the time of surgical resection
Authors: T. E. Johnson, G. A. Luiken, M. M. Quigley, M. Xu, R. M. Hoffman
Journal: Journal of Clinical Oncology (2006)

15503 Background: Surgery for medullary carcinoma of the thyroid can at times be technically challenging to the surgeon. Inducing the cancer cells to be fluorescent would have the potential to improve the surgeon’s ability to quickly and accurately identify and excise all of the malignant tissue. We have previously demonstrated the feasibility of induced tumor fluorescence with fluorophor-tagged anti-tumor antigen antibodies using human colon and breast cancer cell lines. We present here our results using a human medullary carcinoma of the thyroid cell line in the nude mouse model. Methods: A human medullary carcinoma of the thyroid cell line that was demonstrated to express CA 15–3 was used. Thyroid carcinoma cells were subcutaneously implanted in 4 nude mice (3 study mice and 1 control mice). Three weeks after injection, tumor nodules were easily detectable. Using the tail vein method, 3 study mice were injected with fluorophore-tagged anti-CA 15–3 and 1 control mouse with fluorophore-tagged IgG. Mice were examined using a small animal imaging system with a 470 nm light source and appropriate filters. They were also examined using a simple blue LED flashlight fitted with a fixed 470 nm band pass filter for illumination and were observed through filtered goggles. Results: Fluorescence of tumor nodules in the study mice could be seen through the skin. On dissection and exposure of the tumor nodules, this fluorescence was intense and clearly distinguishable from the surrounding normal tissue using either the imaging system or the blue LED. The control mouse injected with fluorophore-tagged IgG and examined in a similar manner revealed no tumor fluorescence. Conclusions: When tumor antigens are known, fluorophore-tagged antibody induced fluorescence is simple, easy to perform, requires no technically complex equipment or operator expertise and could be adapted to thyroid cancer surgery in the academic or community hospital setting. This technology would be indicated in those patients undergoing initial resection of medullary carcinoma of the thyroid as well as in those patients undergoing resection of recurrent disease where accurate identification of tumor tissue may be more difficult and time consuming. No significant financial relationships to disclose.
Haemoconcentration during treatment of acute heart failure with cardiorenal syndrome: from the CARRESS‐HF trial
Authors: Vanessa Blumer, Stephen J. Greene, Jie‐Lena Sun, Bradley A. Bart, Andrew P. Ambrosy, Javed Butler, Adam D. DeVore, Marat Fudim, Adrian F. Hernandez, Steven E. McNulty, G. Michael Felker, Robert J. Mentz
Journal: European Journal of Heart Failure (2019)
The Conquest of Disease Through Animal Experimentation.
Journal: JAMA (1910)

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