tbuckley/cabot-search huggingface dataset:
Vaccine mandates in the US are doing more harm than good
Authors: Allan S Cunningham
Journal: BMJ (2015)

Tightening the rules for non-medical exemptions is not justified and will increase parental mistrust and resistance, argues Allan S Cunningham 

Since my medical career began in 1962 I have seen the harmful effects of nearly all of the vaccine preventable diseases on the US immunization schedule. I have enthusiastically administered many thousands of vaccine doses and am glad that my children and grandchildren are well vaccinated. However, the current attitudes of public health officials about vaccine mandates and exemptions are arrogant and patronizing.

In the US all 50 states and the District of Columbia require children and adolescents to be vaccinated before they attend school, college, or preschool programs.1 Rhode Island has the most extensive requirements, including mandates for vaccination against hepatitis A and B, Haemophilus influenzae type B, rotavirus, human papillomavirus, and influenza.2 Medical exemptions are granted in all jurisdictions, and religious exemptions are granted everywhere but Mississippi and West Virginia. Only 20 states grant personal exemptions. 

The recent US measles outbreak has given rise to a lot of media hyperventilation about vaccine exemptions. There have been calls for outright bans …
A HYBRID DECISION-MAKING STRATEGY WITH INSTANTANEOUS WAVE-FREE RATIO AND FRACTIONAL FLOW RESERVE COULD ENHANCE ADOPTION OF PHYSIOLOGY-GUIDED CORONARY REVASCULARISATION
Authors: Ricardo Petraco da Cunha, Jin Joo Park, Sayan Sen, Sukhjinder Nijjer, Echavarría-Pinto Mauro, Chang-Wook Nam, Kaleab Asrress, Javier Escaned, Amarjit Sethi, Alun Hughes, Jamil Mayet, Iqbal Malik, Ghada Mikhail, Bon-Kwon Koo, Darrel Francis, Simon Redwood, Carlo Di Mario, Justin Davies
Journal: Journal of the American College of Cardiology (2013)
Abstract 14666: Serum Gamma-glytamyl Transferase is a Predictor of Mortality in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention
Authors: Jae Gyung Kim, Jin Jin Kim, Eun Ho Choo, Su Nam Lee, Su-hyun Lee, Dong Hwi Kim, Soo Jin Na, Byung-Hee Hwang, Suk Min Seo, Tae-Hun Kim, Yoon Seok Koh, Mahn Won Park, Sung-Won Jang, Sung-Ho Her, Pum Joon Kim, Jong Min Lee, Sang-Hyun Ihm, Kiyuk Chang, Wook Sung Chung, Ki-Bae Seung, Doo Sun Sim, Keun-Ho Park, Ju Han Kim, Young Joon Hong, Youngkeun Ahn, Myung Ho Jeong
Journal: Circulation (2013)

Background: Serum gamma-glutamyl transferase (GGT) is able to catalyse low-density lipoprotein oxidation, and associated with adverse cardiovascular outcome in patients with ischemic heart disease....
Primary and Acquired Resistance of Colorectal Cancer Cells to Anti-Egfr Antibodies Can Be Overcome By the Treatment with Regorafenib in Combination with Cetuximab
Authors: S. Napolitano, E. Martinelli, D. Vitagliano, G. Martini, C. Cardone, F. De Vita, F. Ciardiello, T. Troiani
Journal: Annals of Oncology (2014)
Abstract P3-05-14: Modeling chemoendocrine therapy for ER+/p53wt luminal breast cancer
Authors: Shiliang A Cao, Elgene Lim, Myles Brown, Shannon T Bailey
Journal: Cancer Research (2015)

Abstract Background ER+ breast cancers are predominantly p53 wildtype (wt). Despite this genotype, these cancers are relatively resistant to chemotherapy-induced apoptosis in the presence of estrogen. Thus, current clinical practice is to administer hormonal therapy and chemotherapy sequentially rather than concurrently. Using the ER+/p53wt cell line MCF-7, we previously demonstrated that ER bound by either the ER agonist estradiol or partial antagonist tamoxifen inhibits the expression of a set of proapoptotic p53 target genes, whereas the full ER antagonist fulvestrant, a selective ER downregulator (SERD), removes the ER-mediated suppression of these genes, sensitizing breast cancer cells to p53-mediated cell death .We hypothesize that effective chemoendocrine therapy requires complete ER antagonism resulting in ER downregulation, increased p53 activity, and ultimately apoptosis. Methods: To model mechanisms of tumor sensitivity and resistance to therapy in vivo, therapeutic experiments were performed in immunodeficient mice bearing ER+/p53wt tumor xenografts derived from a 61-year-old African-American female with grade 2 invasive ductal carcinoma. The mice were randomly assigned to the following treatment groups: A) fulvestrant B) tamoxifen, C) doxorubicin, D) fulvestrant plus doxorubicin, E) tamoxifen plus doxorubicin, and F) control. Tumors were measured weekly for 42 days to determine treatment effects on growth. In addition, RNA was harvested from tumors at an early time point for RNA sequencing to determine genes regulated by the treatments. Results: Combination therapy comprising doxorubicin plus fulvestrant resulted in tumor regression compared with single-agent or doxorubicin plus tamoxifen treatment, which inhibited the growth of tumors but did not lead to their regression. Conclusions: Current paradigms for the treatment of ER+ breast cancer either in the adjuvant or advanced setting have involved the sequential use of endocrine therapy and chemotherapy. This protocol is partially based on evidence of potential antagonism between tamoxifen and chemotherapy as observed in early studies. Our published work in vitro and the preclinical study presented here suggest that complete ER antagonism with SERDs such as fulvestrant is required to overcome the ability of ER to block p53-mediated apoptosis. Our results suggest treatments involving fulvestrant concurrent with chemotherapies involving p53 activation should be considered for the treatment of patients with ER+/p53wt breast cancer. Citation Format: Shiliang A Cao, Elgene Lim, Myles Brown, Shannon T Bailey. Modeling chemoendocrine therapy for ER+/p53wt luminal breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-14.
An elevated body mass (BMI) index predicts for better clinical outcomes in men with metastatic hormone refractory prostate cancer (HRPC)
Authors: S. Halabi, S. Ou, N. J. Vogelzang, E. J. Small
Journal: Journal of Clinical Oncology (2006)

4556 Background: Previous articles have reported that an elevated BMI was associated with an increased risk of biochemical failure in hormone sensitive patients. We asked the question as to whether an elevated BMI predicts for worst clinical outcomes, namely overall survival (OS) and prostate-cancer survival (PCS), among 1,216 men with HRPC. Methods: Patients were enrolled on eight clinical trials conducted by the Cancer and Leukemia Group B (CALGB). Eligible patients had progressive prostate cancer during androgen deprivation therapy (with documented castrate levels of testosterone), an ECOG performance status of 0–2, adequate hematologic, renal and hepatic function. We used the NIH definition to classify patients as: normal (&lt;25 kg/m 2 ), overweight (25–29 kg/m 2 ), mildly obese (30–34 kg/m 2 ), and moderately to severely obese (≥35 kg/m 2 ). PCS was defined as the time from study entry to the time of death due to prostate cancer. The proportional hazards model was used to explore the prognostic significance of BMI in predicting OS and PCS. Results: The median BMI was 27.7 kg/m 2 (inter-quartile range = 25.2–31.0 kg/m 2 ). Twenty three percent (285/1216) of the patients had normal BMI, 46% (555/1216) were overweight, 23% (280/1216) were mildly obese, and 8% (96/1216) were moderately to severely obese. In multivariate analysis, adjusting for age, race, performance status, hemoglobin, PSA, LDH, alkaline phosphatase, testosterone, years since diagnosis, presence of visceral disease and Gleason scores, BMI was a statistically significant predictor of OS and PCS. Compared to normal men, the hazard ratios (HR) of overweight patients was 0.80 (95% CI = 0.69–0.93, p-value = 0.003), for mildly obese patients was 0.86 (95% CI = 0.72–1.02, p-value = 0.087) and for moderately to severely obese men it was 0.60 (95% CI = 0.47–0.78, p-value &lt; 0.001). In addition, the HRs for PCS for overweight patients was 0.83 (95% CI = 0.70–0.97, p-value = 0.023), was 0.88 (95% CI = 0.72–1.06, p-value = 0.179) for mildly obese and for moderately to severely obese was 0.62 (95% CI = 0.47–0.81, p-value = 0.001) compared to men with normal BMI. Conclusions: Contrary to what was reported, these findings demonstrate an inverse relationship between BMI and clinical outcomes in men with HRPC. [Table: see text]
Abstract 4380: IACS-10759: A novel OXPHOS inhibitor which selectively kill tumors with metabolic vulnerabilities
Authors: Marina Protopopova, Madhavi Bandi, Jennifer Bardenhagen, Christopher Bristow, Christopher Carroll, Edward Chang, Ningping Feng, Jason Gay, Mary Geck Do, Jennifer Greer, Marina Konopleva, Polina Matre, Zhijun Kang, Gang Liu, Florian Muller, Timothy Lofton, Timothy McAfoos, Yuting Sun, Melinda Smith, Jay Theroff, Yuanqiang Wu, Lynda Chin, Giulio Draetta, Philip Jones, Carlo Toniatti, M. Emilia Di Francesco, Joseph R. Marszalek
Journal: Cancer Research (2015)

Abstract Tumor cells normally depend on both glycolysis and oxidative phosphorylation (OXPHOS) to provide the energy and macromolecule building blocks needed to enable continued tumor cell growth. Genetic or epigenetic inactivation of one of these two redundant pathways represents a metabolic vulnerability that should be susceptible to an inhibitor of the other pathway. Through an extensive medicinal chemistry campaign, IACS-10759 was identified as a potent inhibitor of complex I of oxidative phosphorylation. In isolated mitochondria or permeabilized cells, ATP production or oxygen consumption was inhibited at single digit nM concentrations in the presence of malate/glutamate, but not succinate. More directly, IACS-10759 inhibited the conversion of NADH to NAD+ in an immunoprecipitated complex I assay at low nM concentrations. Using genetic and pharmacological approaches, the specific complex I subunit inhibited by IACS-10759 has been identified and the mechanism of complex I inhibition is being investigated. Importantly, IACS-10759 is orally bioavailable with excellent physicochemical properties in preclinical species and achieved significant in vivo efficacy with daily oral dosing of 10-25 mg/kg. Specifically, there was a &amp;gt;50 day extension of median survival in an orthotopic AML cell line xenograft and robust regression in DLBCL and GBM xenograft models. In light of these results, as well as its drug like profile IACS-10759 has entered IND enabling studies with first-in-human studies targeted for third quarter of 2015. Citation Format: Marina Protopopova, Madhavi Bandi, Jennifer Bardenhagen, Christopher Bristow, Christopher Carroll, Edward Chang, Ningping Feng, Jason Gay, Mary Geck Do, Jennifer Greer, Marina Konopleva, Polina Matre, Zhijun Kang, Gang Liu, Florian Muller, Timothy Lofton, Timothy McAfoos, Yuting Sun, Melinda Smith, Jay Theroff, Yuanqiang Wu, Lynda Chin, Giulio Draetta, Philip Jones, Carlo Toniatti, M. Emilia Di Francesco, Joseph R. Marszalek. IACS-10759: A novel OXPHOS inhibitor which selectively kill tumors with metabolic vulnerabilities. [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 4380. doi:10.1158/1538-7445.AM2015-4380
Interstitial high dose rate (HDR) brachytherapy for early stage breast cancer
Authors: S. Biggs, P. J. Anderson, R. Mark, T. Neumann, M. Nair
Journal: Journal of Clinical Oncology (2006)

10551 Background: External Beam Radiation Therapy (EBRT) has been the standard of care for breast conservation radiation therapy. Recent data indicates that Interstitial Implant and High Dose Rate (HDR) radiation afterloading compares favorably to EBRT in selected patients. Methods: Patients with Tis, T1, and T2 tumors measuring ≤ 3 cm, negative surgical margins, and negative axillary lymph nodes were judged to be candidates for Interstitial Implant. Results: Between 2000 and 2006, 112 patients underwent Interstitial HDR Implant under Stereotactic Mammographic guidance with conscious sedation and local anesthesia. Conscious sedation consisted of Morphine and Versed. Local anesthesia was given with a mixture of 1% Lidocaine, 0.25% Marcaine, 1:100,000 Epinephrine, and 4% Sodium Bicarbonate neutralizing solution. The implants were placed using a Template with from 3 to 6 planes, and 8 to 43 needles. Catheters were subsequently threaded thru the needles, and the needles removed. Catheter spacing was 1.0 to 1.5 cm. Radiation Treatment planning was performed using CT Scanning. Treatment volumes ranged from 25 cm 3 to 359 cm 3 . The breast implant volume received 3400 cGy in 10 fractions via HDR prescribed to the Planning Target Volume, given BID over 5 days. The procedure was well tolerated. No patient required hospital admission. With a median follow-up 36 months (range 6–60 months), local recurrence occurred in 2.7% (3/112). Cosmetic results were good to excellent in 85.7% (96/112) of the patients. Wound healing complications developed in 7.1% (8/112). Three of these patients had received anthracycline based Chemotherapy. The other five had large (&gt; 200 cm 3 ) implant volumes and catheter spacing of 1.5 cm. Two patients healed after 6 months of conservative treatment. Surgery was required in six patients who developed fat necrosis. Conclusions: With median 36 month follow-up, Breast Conservation radiation therapy utilizing Interstitial HDR Implant has yielded local recurrence rates and cosmetic results which compare favorably to EBRT in selected patients. Treatment with anthracycline based Chemotherapy and large (&gt; 200 cm 3 ) implant volumes appear to be relative contraindications to Interstitial HDR Implant. Finally, catheter spacing of 1 cm yielded optimal dosimetry and minimized complications. No significant financial relationships to disclose.
Prospective Community Studies Linking Cognitive Deficits to Subclinical Symptoms and a Step Toward Precision Medicine
Authors: Ruben C. Gur
Journal: JAMA Psychiatry (2015)

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 Psychiatry 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 Psychiatry journal
Ebola: missed opportunities for Europe–Africa research
Authors: Giuseppe Ippolito, Simone Lanini, Philippe Brouqui, Antonino Di Caro, Francesco Vairo, Salim Abdulla, Francesco Maria Fusco, Sanjeev Krishna, Maria Rosaria Capobianchi, Henry Kyobe-Bosa, David J M Lewis, Vincenzo Puro, Roman Wolfel, Tatjana Avsic-Zupanc, Osman Dar, Peter Mwaba, Matthew Bates, David Heymann, Alimuddin Zumla
Journal: The Lancet Infectious Diseases (2015)
Targeting the inhibitor of apoptosis
Authors: Wayne Fairbrother
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

SY26-01 

The inhibitor of apoptosis (IAP) proteins are major regulators of apoptosis that bind to and inhibit caspases 3, 7, and/or 9. Overexpression of IAP proteins has been demonstrated to confer protection against a variety of pro apoptotic stimuli, including chemotherapies, and is a marker for poor prognosis in a variety of solid tumors and hematologic malignancies. All IAP proteins contain one to three copies of the baculoviral IAP repeat (BIR) domain, zinc-binding domains of about 80 amino acids, that are necessary for their interactions with a number of cytosolic target proteins, including activated caspases 3, 7, and/or 9. Antagonism of the IAP protein mediated inhibition of these caspases is required for caspase dependent cell death, and can be achieved by the mitochondrial protein second mitochondria derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO), which is released into the cytoplasm in response to pro apoptotic stimuli. The pro apoptotic function of Smac/DIABLO is dependent on a conserved four residue IAP protein interaction motif (A-V/I-P/A-I/F/Y) found at the N terminus of the mature, post translationally processed, protein. Structural studies have shown that such N terminal peptides bind to a surface groove on the IAP protein BIR domains. The Smac-binding groove of XIAP BIR3 also makes critical contacts with an IAP protein interacting motif located at the N terminus of the small subunit of caspase-9. The use of structure-based design to identify small molecules that potently antagonize IAP protein interactions will be discussed. These small-molecule IAP protein antagonists induce apoptosis in select cancer cell lines and have proven efficacious at inhibiting tumor growth in mouse xenograft models of breast cancer, NSCLC, pancreatic cancer, melanoma, and colon cancer. In vitro studies have established that IAP protein antagonists induce cell death that is dependent on de novo protein biosynthesis and TNF signaling. Remarkably, binding of small-molecule IAP protein antagonists to the BIR3 domains of c-IAP1 or 2 results in induction of auto-ubiquitination activity and rapid proteasomal degradation of these proteins. IAP protein antagonists also result in activation of the NF-kappaB signaling pathways and induction of TNFalpha expression. Given that c-IAP1 and 2 are recruited to the proximal TNFR1-signaling complexes where they cooperate with TRAF2 to block caspase-8 activation, their proteasomal degradation following IAP protein antagonist-induced auto-ubiquitination likely perturbs TNF signaling to favor an apoptotic outcome. By negating the activities of three antiapoptotic proteins, c-IAP1 and 2 through induced degradation, and XIAP through direct antagonism of caspase inhibition, IAP protein antagonists establish an intracellular environment that allows caspase activation, and thus advance an apoptotic fate when TNFalpha is produced in response to induction of NF-kappaB activity.
Breaking New Ground in Health Services Research
Authors: Magrielle H. Eisen, David M. Rubin
Journal: JAMA Pediatrics (2015)

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
Abstract P382: Fried Food Consumption is Associated with a Higher Risk of Heart Failure among US Male Physicians
Authors: Luc Djousse, Andrew Petrone, John M Gaziano
Journal: Circulation (2015)

Background: While previous studies have reported a positive relation of fried food consumption with type 2 diabetes, hypertension, and obesity, no previous study has examined the relation of total fried food intake with risk of heart failure (HF) in a prospective cohort. Objective: To test the hypothesis that fried food consumption is positively associated with risk of HF in male physicians. Methods: A prospective cohort of 19,968 participants from the Physicians’ Health Study. Frequency of fried food consumption was assessed between 1999 and 2002 using a food frequency questionnaire and HF was ascertained through annual follow-up questionnaires with validation in a subsample. We used Cox regression to estimate multivariable adjusted hazard ratios of HF. Results: During a median follow-up of 10.6 years, 862 cases of HF occurred. The mean age at baseline was 66.4 ± 9.2 years. Median frequency of fried food consumption was &lt;1 time per week. Multivariable adjusted hazard ratios (95% CI) were: 1.0 (ref), 1.18 (1.01-1.37), 1.25 (1.02-1.54), and 1.68 (1.19-2.36) for fried food consumption of &lt;1/week, 1-3/week, 4-6/week, and 7+/week, respectively (p for linear trend: 0.0004), after adjustment for age, alcohol use, smoking, exercise, and history of myocardial infarction, coronary artery bypass graph or angioplasty (Fig). Additional adjustment of total trans fats did not alter the findings. In a secondary analysis, body mass index did not modify the relation of fried foods with HF risk. Conclusions: Our data show a positive association between fried food intake and risk of HF in US male physicians.
Culprit Only or Multivessel Percutaneous Coronary Intervention in Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Disease
Authors: Mikkel Hougaard, Lisette Okkels Jensen, Per Thayssen, D Körmendiné Farkas, C J Terkelsen, H H Tilsted, M Maeng, Anders Junker, J F Lassen, Knud Nørregaard Hansen, E Puho, H T Sørensen, L Thuesen
Journal: Journal of the American College of Cardiology (2011)
Validation of human small-airway measurements using endobronchial optical coherence tomography: an observational study
Authors: Yu Chen, Ming Ding, Wei-Jie Guan, Wei-Zhan Luo, Chang-Hao Zhong, Mei Jiang, Wei Wang, Ju-Hong Jiang, Ying-Ying Gu, Shi-Yue Li, Nan-Shan Zhong
Journal: The Lancet (2015)
Pulmonary Vein Isolation Using the Visually Guided Laser Balloon
Authors: Srinivas R. Dukkipati, Frank Cuoco, Ilana Kutinsky, Arash Aryana, Tristram D. Bahnson, Dhanunjaya Lakkireddy, Ian Woollett, Ziad F. Issa, Andrea Natale, Vivek Y. Reddy
Journal: Journal of the American College of Cardiology (2015)
Dorsal Anterior Cingulate Cortex: A Bottom-Up View
Authors: Sarah R. Heilbronner, Benjamin Y. Hayden
Journal: Annual Review of Neuroscience (2016)

The dorsal anterior cingulate cortex (dACC) has attracted great interest from neuroscientists because it is associated with so many important cognitive functions. Despite, or perhaps because of, its rich functional repertoire, we lack a single comprehensive view of its function. Most research has approached this puzzle from the top down, using aggregate measures such as neuroimaging. We provide a view from the bottom up, with a focus on single-unit responses and anatomy. We summarize the strengths and weaknesses of the three major approaches to characterizing the dACC: as a monitor, as a controller, and as an economic structure. We argue that neurons in the dACC are specialized for representing contexts, or task-state variables relevant for behavior, and strategies, or aspects of future plans. We propose that dACC neurons link contexts with strategies by integrating diverse task-relevant information to create a rich representation of task space and exert high-level and abstract control over decision and action.