tbuckley/cabot-search huggingface dataset:
Performing Survival Analyses in the Presence of Competing Risks: A Clinical Example in Older Breast Cancer Patients
Authors: Nienke A. de Glas, Mandy Kiderlen, Jan P. Vandenbroucke, Anton J. M. de Craen, Johanneke E. A. Portielje, Cornelis J. H. van de Velde, Gerrit-Jan Liefers, Esther Bastiaannet, Saskia Le Cessie
Journal: JNCI Journal of the National Cancer Institute (2015)

An important consideration in studies that use cause-specific endpoints such as cancer-specific survival or disease recurrence is that risk of dying from another cause before experiencing the event of interest is generally much higher in older patients. Such competing events are of major importance in the design and analysis of studies with older patients, as a patient who dies from another cause before the event of interest cannot reach the endpoint. In this Commentary, we present several clinical examples of research questions in a population-based cohort of older breast cancer patients with a high frequency of competing events and discuss implications of choosing models that deal with competing risks in different ways. We show that in populations with high frequency of competing events, it is important to consider which method is most appropriate to estimate cause-specific endpoints. We demonstrate that when calculating absolute cause-specific risks the Kaplan-Meier method overestimates risk of the event of interest and that the cumulative incidence competing risks (CICR) method, which takes competing risks into account, should be used instead. Two approaches are commonly used to model the association between prognostic factors and cause-specific survival: the Cox proportional hazards model and the Fine and Gray model. We discuss both models and show that in etiologic research the Cox Proportional Hazards model is recommended, while in predictive research the Fine and Gray model is often more appropriate. In conclusion, in studies with cause-specific endpoints in populations with a high frequency of competing events, researchers should carefully choose the most appropriate statistical method to prevent incorrect interpretation of results.
Online Advertising for Cancer Prevention: Google Ads and Tanning Beds
Authors: Wilmarie Cidre Serrano, Mary-Margaret Chren, Jack S. Resneck, Nepheli N. Aji, Sherry Pagoto, Eleni Linos
Journal: JAMA Dermatology (2015)

through ratio of 1% is considered adequate for commercial advertisements.Although we were not able to formally compare the efficacy of different advertisements, the click-through rates varied among advertisement and message categories, with the appearance-based messages performing the worst.Discussion | To promote healthy behaviors, we need approaches that reach large, targeted audiences.The enormous population using search engines and the ability to target messages based on search key words make online advertising a potentially useful and relatively inexpensive tool for public health.Our pilot study demonstrated the feasibility of using online advertising to deliver targeted prevention messages related to indoor tanning and skin cancer.However, the effect of these advertisements on health behavior remains unknown.Further studies of this approach are needed to explore the characteristics of messages that generate views and clicks, and ultimately to determine whether this type of intervention successfully changes behaviors.
Lucentis offers treatment alternative for diabetic retinopathy, trial finds
Authors: J. Wise
Journal: BMJ (2015)

The drug ranibizumab (Lucentis) injected into the eye seems to be an effective alternative treatment for proliferative diabetic retinopathy when compared with the standard laser therapy, a multicentre randomised trial published in JAMA has found.1

The laser treatment, panretinal photocoagulation, is the standard treatment for reducing severe visual loss from diabetic retinopathy. However, the treatment can cause permanent peripheral visual field loss and decreased night vision and may exacerbate diabetic macular oedema.

The non-inferiority study included 305 adults with proliferative diabetic retinopathy at 55 sites in the United States. Of these patients, 89 had both eyes …
Targeting Endogenous Repair Pathways after AKI
Authors: Benjamin D. Humphreys, Vincenzo Cantaluppi, Didier Portilla, Kai Singbartl, Li Yang, Mitchell H. Rosner, John A. Kellum, Claudio Ronco
Journal: Journal of the American Society of Nephrology (2015)

AKI remains a highly prevalent disease associated with poor short– and long–term outcomes and high costs. Although significant advances in our understanding of repair after AKI have been made over the last 5 years, this knowledge has not yet been translated into new AKI therapies. A consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 and reviewed new evidence on successful kidney repair to identify the most promising pathways that could be translated into new treatments. In this paper, we provide a summary of current knowledge regarding successful kidney repair and offer a framework for conceptualizing the therapeutic targeting that may facilitate this process. We outline gaps in knowledge and suggest a research agenda to more efficiently bring new discoveries regarding repair after AKI to the clinic.
CALGB/SWOG 80405: Phase III Trial of Irinotecan/5-FU/Leucovorin (FOLFIRI) or Oxaliplatin/5-FU/Leucovorin (MFOLFOX6) with Bevacizumab (BV) or Cetuximab (CET) for Patients (PTS) with KRAS Wild-Type (WT) Untreated Metastatic Adenocarcinoma of the Colon
Authors: A. Venook, D. Niedzwiecki, H.J. Lenz, F. Innocenti, M.R. Mahoney, B. O'Neil, J. Shaw, B. Polite, H. Hochster, J. Atkins, R. Goldberg, R. Mayer, R. Schilsky, M. Bertagnolli, C. Blanke
Journal: Annals of Oncology (2014)
First human experience with the 17-beta-estradiol–eluting stent
Authors: Alexandre Abizaid, Mariano Albertal, Marco A Costa, Andrea S Abizaid, Rodolfo Staico, Fausto Feres, Luiz A Mattos, Amanda G.M.R Sousa, Jeffrey Moses, Nicholas Kipshidize, Gary S Roubin, Roxana Mehran, Gishel New, Martin B Leon, J.Eduardo Sousa
Journal: Journal of the American College of Cardiology (2004)
Optimized extracorporeal shock-wave therapy improved pain and functioning in chronic plantar fasciitis
Authors: Jason Springer, Robert G. Badgett
Journal: Annals of Internal Medicine (2015)

Source Citation Gollwitzer H, Saxena A, DiDomenico LA, et al. Clinically relevant effectiveness of focused extracorporeal shock wave therapy in the treatment of chronic plantar fasciitis: a randomized, controlled multicenter study. J Bone Joint Surg Am. 2015;97:701-8. 25948515
Serum Creatinine and Renal Function
Authors: A S Levey, R D Perrone, N E Madias
Journal: Annual Review of Medicine (1988)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine
Authors: Jacob D. Brown, Maythem Saeed, Loi Do, Joao Braz, Allan I. Basbaum, Michael J. Iadarola, David M. Wilson, William P. Dillon
Journal: Science Translational Medicine (2015)

Delivery of resiniferatoxin under CT guidance around lumbar dorsal root ganglia in pigs resulted in selective deletion of nociceptive neurons and lasting analgesia.
Plasma IL-16 Concentration and Recurrent Wheeze At Age 3 in Inner-City Children in the Ureca Birth Cohort
Authors: William W. Cruikshank, Marina Tuzova, Katy Jaffee, George T. O'Connor, Gordon R. Bloomberg, Meyer Kattan, Robert A. Wood, James Gern
Journal: Journal of Allergy and Clinical Immunology (2013)
Is L-methionine a trigger factor for Alzheimer’s-like neurodegeneration?: Changes in Aβ oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice
Authors: Cheril Tapia-Rojas, Carolina B. Lindsay, Carla Montecinos-Oliva, Macarena S. Arrazola, Rocio M. Retamales, Daniel Bunout, Sandra Hirsch, Nibaldo C. Inestrosa
Journal: Molecular Neurodegeneration (2015)

L-methionine, the principal sulfur-containing amino acid in proteins, plays critical roles in cell physiology as an antioxidant and in the breakdown of fats and heavy metals. Previous studies suggesting the use of L-methionine as a treatment for depression and other diseases indicate that it might also improve memory and propose a role in brain function. However, some evidence indicates that an excess of methionine can be harmful and can increase the risk of developing Type-2 diabetes, heart diseases, certain types of cancer, brain alterations such as schizophrenia, and memory impairment. Here, we report the effects of an L-methionine-enriched diet in wild-type mice and emphasize changes in brain structure and function. The animals in our studypresented 1) higher levels of phosphorylated tau protein, 2) increased levels of amyloid-β (Aβ)-peptides, including the formation of Aβ oligomers, 3) increased levels of inflammatory response,4) increased oxidative stress, 5) decreased level of synaptic proteins, and 6) memory impairment and loss. We also observed dysfunction of the Wnt signaling pathway. Taken together, the results of our study indicate that an L-methionine-enriched diet causes neurotoxic effects in vivo and might contribute to the appearance of Alzheimer's-like neurodegeneration.
The Consult Guys - A Case of Hypertension: Overcoming Resistance Requires Change
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2015)

Web Exclusives17 November 2015The Consult Guys - A Case of Hypertension: Overcoming Resistance Requires ChangeFREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W15-0010 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe USPSTF Recommendation on Blood Pressure Screening 17 November 2015Volume 163, Issue 10Page: CG1KeywordsDisclosureHypertensionResearch grantsResearch reporting guidelines ePublished: 17 November 2015 Issue Published: 17 November 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.Loading ...
Approach to undiagnosed exudative pleural effusion: The diagnostic yield of blind pleural biopsy
Authors: Mehrdad Solooki, Majid Malekmohamad
Journal: European Respiratory Journal (2011)

Blind pleural biopsy has traditionally been performed to investigate the etiology of exudative pleural effusion in which the initial thoracentesis has been non- diagnostic. This study examines the role of blind Abrams pleural biopsy in investigation of the exudative pleural effusion in the largest tertiary pulmonary center in Iran (Massih-Daneshvari Medical Center).   Method:  All patients with pleural effusion admitted from September 2007 to April 2009 entered a prospective cohort study. Patients with exudative pleural effusion underwent blind Abram pleural biopsy if the initial thoracentesis was non-diagnostic. Patients with non-diagnostic blind biopsy underwent surgical biopsy or other investigations based on physicians decision.   Results:  Blind percutaneous pleural biopsy were performed in 171 patients. For all diagnoses, blind biopsy had a sensitivity of 70.1% and negative predictive value of 14.8%. For malignancy and TB diagnosis, sensitivity value was 58.9% and 88.1% and negative predictive value 63.2% and 93.6% respectively.Overall malignancy was diagnosed in 95 (58.6%) and TB in 59 (36.4%) of patients.   Conclusions:  Blind Abrams needle biopsy was diagnostic in apporximatly three out four patients presenting with undiagnosed exudative pleural effusion. The data support the use of the Abrams needle in the investigation of pleural effusion especially in lesser developed countries.
Phase I study of 5-fluorouracil in children and young adults with recurrent ependymoma
Authors: Karen D. Wright, Vinay M. Daryani, David C. Turner, Arzu Onar-Thomas, Nidal Boulos, Brent A. Orr, Richard J. Gilbertson, Clinton F. Stewart, Amar Gajjar
Journal: Neuro-Oncology (2015)

We report a phase I study to examine the pharmacokinetics, safety, and recommended dosage of weekly intravenous bolus 5-fluorouracil (5-FU) in children and young adults with recurrent ependymoma. Patients 22 years of age or less with recurrent ependymoma were treated with bolus dosage 5-FU weekly for 4 weeks followed by a 2-week rest period, defining one cycle. Patients could continue on therapy for 16 cycles. The starting 5-FU dosage was 500 mg/m2. Dose-limiting toxicity was determined after one cycle. Patients were initially enrolled according to a rolling-6 design; subsequent dose re-escalation phase was based on a 3 + 3 design. We treated patients at 400 (n = 6), 500 (n = 15), and 650 (n = 5) mg/m2, with de-escalation due to toxicity. Twenty-three of twenty-six patients enrolled were evaluable. Five patients experienced grade 4 neutropenia (n = 2: 650 mg/m2; n = 3: 500 mg/m2). One patient experienced grade 3 diarrhea. At 500 mg/m2, the median 5-FU maximal concentration, AUC0–∞, and alpha half-life were 825 µM, 205 µM × h, and 9.9 min, respectively. Interim analysis revealed an association between hematologic toxicity and prior number of chemotherapeutic regimens (P = .03). The study was amended to re-escalate the dosage in a less heavily pretreated cohort of patients. These phase I clinical data provide initial pharmacokinetic parameters to describe i.v. bolus 5-FU disposition in children with recurrent ependymoma. Tumor exposures effective in preclinical testing can be achieved with tolerable bolus dosages in patients. Bolus 5-FU is well tolerated and possesses antitumor activity.
How the local built environment affects physical activity behaviour in older adults in the UK: a cross-sectional analysis linked to two national cohorts
Authors: Sophie Hawkesworth, Richard Silverwood, Triantafyllos Pliakas, Kiran Nanchahal, Barbara Jefferis, Claudio Sartini, Antoinette Amuzu, Ben Armstrong, Juan-Pablo Casas, Richard Morris, Peter Whincup, Karen Lock
Journal: The Lancet (2015)
Adjuvant chemotherapy for high-risk squamous-cell carcinoma of the head and neck.
Authors: J T Johnson, E N Myers, V L Schramm, D G Mayernik, T A Nolan, B A Sigler, R L Wagner
Journal: Journal of Clinical Oncology (1987)

A prospective clinical trial was developed to evaluate efficacy, toxicity, and patient compliance to adjuvant chemotherapy following surgery and postoperative radiation therapy in patients with squamous-cell carcinoma of the head and neck with extracapsular spread of tumor in cervical metastases. Following postoperative radiation therapy, 18 courses of methotrexate (MTX) and 5-fluorouracil (5-FU) were administered over 6 months. Fifty patients were registered. A total of 771 doses were administered. Dose reduction was required 72 times. Therapy was stopped in one patient (2%) because of toxicity. Three patients (6%) refused to complete the adjuvant therapy. Adjusted 2-year no evidence of disease (NED) survival is 66%. This study demonstrates that patients with advanced squamous-cell carcinoma of the head and neck can undertake an aggressive program of adjuvant MTX/5-FU with acceptable compliance and toxicities. Preliminary data generated in this nonrandomized study support the call for a prospective randomized multiinstitutional trial of this program.
Abstract 1529: MYC and HIF-2alpha cooperates in oral squamous carcinoma cell self-renewal during hypoxia
Authors: Hong Li, Joyeeta Talukdar, Sora Sandhya, Seema Bhuyan, Sukanya Gayan, Anupam Sarma, Reza Bayat Mokhtari, Dean W. Felsher, Herman Yeger, Bikul Das
Journal: Cancer Research (2015)

Abstract Oral squamous cell carcinoma (OSCC) is a global health challenge. The overall survival rate of this devastating disease has not significantly changed, and the biology of this type of cancer also remain largely unexplored. To enhance the understanding of this disease through global heath cancer research collaborative effort, we have set up an international collaboration between Forsyth Institute, Cambridge, and KaviKrishna laboratory, which is located in Kamrup district of Assam, having highest incidence of oral cancer in the world. Through this collaborative effort we intend to explore the role of hypoxia in oral cancer progression, metastasis and therapy resistance. Method: We used an oral squamous cell carcinoma cell line SSC25 for this purpose, and performed several experiments using a well-described in vitro assay of CSC self-renewal under hypoxia. Results: We identified a rare ABCG2+ expressing, highly tumorigenic cell population in SSC-25 having cancer stem cell (CSC) like characteristics in the in vivo serial transplantation assay, as well as high metastatic activity to bone marrow of NOD/SCID mice. The ABCG2+ cells, when exposed to hypoxia (&amp;lt;0.1% O2, 24 hours), exhibited enhanced expression and transcriptional activity of MYC, and HIF-2alpha. ChIP assay revealed that HIF-2alpha directly binds to MYC in ABCG2+ cells. siRNA inhibition of HIF-2alpha significantly reduced hypoxia-induced MYC expression and transcriptional activity in ABCG2+ cells. Finally, in clinical OSCC specimens, we confirmed the expression of MYC, HIF-2alpha and ABCG2 expression by immunohistochemistry. Conclusion: These data indicate that MYC oncogene play important role in the self-renewal of oral cancer cells during hypoxia. Citation Format: Hong Li, Joyeeta Talukdar, Sora Sandhya, Seema Bhuyan, Sukanya Gayan, Anupam Sarma, Reza Bayat Mokhtari, Dean W. Felsher, Herman Yeger, Bikul Das. MYC and HIF-2alpha cooperates in oral squamous carcinoma cell self-renewal during hypoxia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1529. doi:10.1158/1538-7445.AM2015-1529
Abstract 1595: Analysis of circulating epithelial and EMT-like CTCs in pancreatic cancer using a sensitive microfluidic CTC capture device
Authors: Mina Zeinali, Vasudha Murlidhar, Shamileh Fouladdel, Mathius Hafner, Shimeng Shao, Ebrahim Azizi, Max S. Wicha, Kyle Cuneo, Diane M. Simeone, Sunitha Nagrath
Journal: Cancer Research (2015)

Abstract Background &amp; Aims: A critical factor in the poor outcomes in pancreatic cancer is due to it's silent nature until late in the disease process, so early detection has remained a major issue in this type of cancer. Detection, quantification, and molecular characterization of Epithelial circulating tumor cells (CTCs) as well as Epithelial-to-Mesenchymal Transition (EMT)-like CTCs in peripheral blood have been recognized as a means of “liquid biopsy” technique in the diagnosis of cancer and metastasis. Methods: A modified version of CTC chip, CTC Carpet chip was used to investigate the inextricable relationship between circulating epithelial and EMT-like CTCs in 40 pancreatic cancer patients at both protein and RNA levels. Results: The recovery from whole blood spiked with different cancer cell line was validated, achieving a mean efficiency of ∼100% for both HT-29 and Panc-1 cell lines compared to &amp;lt;80% for PC-3 cell line. Out of 40 patients, 38 patients had ≥5 CK+ CTCs with a mean of 21.84 per mL and all 40 samples had ≥ 15 Vim+ CTCs with mean of 89.77 per mL of whole blood. Up to 67 CK+ epithelial and 257 Vim+ EMT like CTCs were detected in these set of samples. The results indicated the significant differences between the numbers of Epithelial CTCs vs. EMT-like CTCs in both stage I-II and IV of these 40 pancreatic cancer patients’ samples. Conclusion: Although the isolation of CTCs from pancretic cancer is possible nowadays, investigation of their clinical utility has proven less successful than the other cancer types, due to poor sensitivity of many CTC assays for patients with PDAC. Herein, we present an integrated microfluidic technology- and biology-based translational approach using bioengineering tools to identify and study the biological relevance of rare CTCs including both circulating epithelial and EMT-like tumor cells simultaneously from the peripheral blood of pancreatic cancer patients by using multiple markers of interest. Citation Format: Mina Zeinali, Vasudha Murlidhar, Shamileh Fouladdel, Mathius Hafner, Shimeng Shao, Ebrahim Azizi, Max S. Wicha, Kyle Cuneo, Diane M. Simeone, Sunitha Nagrath. Analysis of circulating epithelial and EMT-like CTCs in pancreatic cancer using a sensitive microfluidic CTC capture device. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1595. doi:10.1158/1538-7445.AM2015-1595