tbuckley/cabot-search huggingface dataset:
Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H1N1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice
Authors: I-Na Lu, Sophie Farinelle, Aurélie Sausy, Claude P Muller
Journal: Cellular and Molecular Immunology (2016)

The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not clear. Here we identified a mouse CD4 T-cell epitope that encompasses residues HA2113-131 from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, TNF-α and IFN-γ production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor β sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H1N1 influenza virus. Thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune response against influenza virus infection.
RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features
Authors: V I Gaidzik, V Teleanu, E Papaemmanuil, D Weber, P Paschka, J Hahn, T Wallrabenstein, B Kolbinger, C H Köhne, H A Horst, P Brossart, G Held, A Kündgen, M Ringhoffer, K Götze, M Rummel, M Gerstung, P Campbell, J M Kraus, H A Kestler, F Thol, M Heuser, B Schlegelberger, A Ganser, L Bullinger, R F Schlenk, K Döhner, H Döhner
Journal: Leukemia (2016)
Simple decision rules can reduce reinjury risk by 84% after ACL reconstruction: the Delaware-Oslo ACL cohort study
Authors: Hege Grindem, Lynn Snyder-Mackler, Håvard Moksnes, Lars Engebretsen, May Arna Risberg
Journal: British Journal of Sports Medicine (2016)

Knee reinjury after ACL reconstruction is common and increases the risk of osteoarthritis. There is sparse evidence to guide return to sport (RTS) decisions in this population.To assess the relationship between knee reinjury after ACL reconstruction and (1) return to level I sports, (2) timing of RTS and (3) knee function prior to return.106 patients who participated in pivoting sports participated in this prospective 2-year cohort study. Sports participation and knee reinjury were recorded monthly. Knee function was assessed with the Knee Outcome Survey-Activities of Daily Living Scale, global rating scale of function, and quadriceps strength and hop test symmetry. Pass RTS criteria were defined as scores >90 on all tests, failure as failing any.Patients who returned to level I sports had a 4.32 (p=0.048) times higher reinjury rate than those who did not. The reinjury rate was significantly reduced by 51% for each month RTS was delayed until 9 months after surgery, after which no further risk reduction was observed. 38.2% of those who failed RTS criteria suffered reinjuries versus 5.6% of those who passed (HR 0.16, p=0.075). More symmetrical quadriceps strength prior to return significantly reduced the knee reinjury rate.Returning to level I sports after ACL reconstruction leads to a more than 4-fold increase in reinjury rates over 2 years. RTS 9 months or later after surgery and more symmetrical quadriceps strength prior to return substantially reduce the reinjury rate.
Low Psoas Muscle/BMI Ratio Is a Bad Prognostic Index Of Non-Relapse Survival After Allogeneic Stem Cell Transplantation
Authors: Soo Jeong Kim, Yundeok Kim, Doh Yu Hwang, Shin Young Hyun, Ji Eun Jang, Jung Yeon Lee, June-Won Cheong, Jin Seok Kim, Yoo Hong Min
Journal: Blood (2013)
Chronic pain as a third pathologic emotion
Authors: D W Swanson
Journal: American Journal of Psychiatry (1984)

Chronic pain is often difficult to explain on the basis of objective findings. Various theoretical models are available. The hypothesis advanced here is that chronic nonprogressive pain is primarily a neuropsychologic event and that it is in the same category as the emotions of anxiety and depression, with each emotional state having neurochemical correlates now achieving some definition. General systems theory and analogy are used to compare acute and chronic pain with the phenomena of fear and anxiety and also with grief and depression.
Corporate Funding of Nutrition Research and Unjustified Conclusions—Reply
Authors: Marion Nestle
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
Update on PSA Testing
Authors: Mark L. Gonzalgo, H. Ballentine Carter
Journal: Journal of the National Comprehensive Cancer Network (2007)

The use of prostate-specific antigen (PSA) testing for prostate cancer screening has increased dramatically over the past decade. Determining the most efficient way to use PSA testing and how to interpret total PSA levels and changes in PSA values over time remain challenging. Guidelines for early detection of prostate cancer have a direct impact on the number of unnecessary tests performed and are critical for developing a successful screening approach for prostate cancer. The age at which PSA screening should begin, PSA testing intervals, and the importance of understanding fluctuations in PSA values over time are discussed in the framework of recent discoveries in the field. Results from ongoing randomized trials will confirm whether prostate cancer screening is an effective method for reducing deaths from prostate cancer and what approaches will provide the most cost-effective screening strategies.
Circulating tumor cell capture and analysis in a multicenter SWOG-coordinated prostate cancer trial.
Authors: A. Goldkorn, T. Xu, B. Lu, A. Williams, L. M. Fink, C. M. Tangen, P. Twardowski, Y. Tai, D. I. Quinn, R. Cote
Journal: Journal of Clinical Oncology (2010)

TPS342 Background: Prostate cancer biomarkers are urgently needed to better inform treatment decisions. Recent studies have demonstrated that quantification of peripheral blood circulating tumor cells (CTCs) predicts response to therapy and overall survival in advanced prostate cancer. However, present methods for CTC collection are limited by low yield, complex techniques, and expensive equipment, and they provide little phenotypic information about the CTCs themselves. We have developed a new microfilter platform that simply and reliably traps and enriches the CTC population from peripheral blood, enabling enumeration and further study of these cells. To test whether our microfilter can serve as a simple yet reliable new predictive platform for CTC collection, quantification, and phenotypic analysis, we have activated a correlative CTC biomarker study that “piggybacks” onto S0421, a SWOG cooperative group national protocol studying atrasentan in combination with docetaxel in castration resistant prostate cancer. Methods: In this ongoing multicenter trial, blood samples are drawn at 3 time points before and during treatment. Each sample is processed through the microfilter, and the captured CTCs are analyzed in three ways: 1. Absolute and post-treatment changes in microfilter CTC counts with parallel analysis on the FDA-approved Cell Search platform. 2. Expression of relevant biomarkers on microfilter- trapped CTCs; specifically, endothelin receptor A for atrasentan response, type III β-tubulin for docetaxel response, and CD44 for an aggressive progenitor/metastatic phenotype. 3. Telomerase activity in microfilter-enriched cells. Data is relayed to SWOG Statistical Center for analysis and correlation with clinical outcomes and therapy response in S0421. As of 12/2009, 131 patients have been accrued, with a final goal of 600 samples from 200 patients. This large-scale correlative biomarker study will determine if the quantity and characteristics of CTCs captured on our novel platform can predict clinical outcome and response to therapy, thus enhancing our ability to assess therapeutic efficacy in real time and contributing to optimized, evidence-based, individualized patient management. No significant financial relationships to disclose.
Soundings: Geese of a different feather
Authors: George Dunea
Journal: BMJ (2003)

The cost of drugs in America has become so high that those who can afford them complain, and those who cannot afford them sometimes go without. Not a week passes without some newspaper commenting about high drug prices and exploding hospital or state budgets. Many people complain about the excessive cost of the drugs required to treat their rheumatoid arthritis, their depression, hypertension, or peptic ulcers; or grumble about the high price of eradicating their Helicobacter infection; but all this pales into insignificance compared with the price of some of the new anticancer or immunomodulating drugs. There has been much talk about reforms, new legislation, about importing less expensive drugs from Canada or other countries, but so far precious little has happened, and the people are upset.

To these complaints the drug makers counter by arguing that developing a new drug and getting it on to the market is expensive ($500m/£313m/€475m per successful drug), and that the shareholders are demanding, the reviewing bureaucracy ponderous and capricious, the required investment large, and the risk of failure high. They remind us that the new drugs have cured many once fatal diseases and revolutionised modern medicine, and suggest that we should take care not to kill the goose that has laid so many golden eggs.

Yet existing data indicate that in 1998 the largest 10 drug companies spent only 11.1% of their sales revenue on research and development. Moreover, according to Prescrire, the outspoken Parisian review of drugs, only 15% of new drugs are really innovative, most products being “me too” drugs.

Traditionally doctors have been able to save their patients money by prescribing generic drugs. But in 2002 the price of generic drugs rose twice as fast as that of brand name drugs. Within a few years the price of a commonly used antihypertensive drug has risen tenfold, and for some generic medicines the cost has risen by 1000%. Yet such drugs require no research, no massive investment; they merely feed an extensive food chain of manufacturers and middle men—wholesalers, managed care distributors, and pharmacies—geese of a different feather that to our knowledge have not laid any particularly golden eggs.
Prognostic significance of MIB-1 labeling indices for oligodendroglial tumors
Authors: U. Abacioglu, M. Sengoz, E. Tezcanli, S. Akpulat, S. Peker, A. Sav
Journal: Journal of Clinical Oncology (2005)

1533 Background: Oligodendroglial tumors (OT) are the third most common glial tumors. MIB-1 is an antibody against Ki-67 nuclear protein whose level is indicative of proliferative activity in cells within a tumor. We aimed to investigate the prognostic factors for treatment outcome in patients with OT and determine the prognostic value of MIB-1 labeling index (LI). Methods: 56 consecutive patients who received postoperative radiotherapy (RT) between April 1997 and June 2003 for a diagnosis of OT were included in the study. 32 patients (57%) presented with pure oligodendroglioma (OD) and 24 (43%) with mixed oligoastrocytoma (OA). 19 tumors (34%) were grade 2, and 37 (66%) grade 3. Male/Female ratio was 15/41 and ages ranged between 13–82 years (median 41.5). Histopathologic diagnosis was performed after gross total resection in 21, subtotal resection in 28 and stereotactic biopsy in 7 patients. Postoperative KPS scale ranged between 40 and 100 (median 90). All patients received postoperative RT to a median total dose of 60 Gy (range, 54–66 Gy). 20% of the patients received adjuvant PCV chemotherapy (CT). Results: Median PFS and OS rates for all patients were 40 months and 52 months, respectively. In univariate analysis patients with grade 2 tumors (p<0.001), OD histopathology (p=0.043), KPS>70 (p<0.001), age ≤45 years (p<0.001), history of seizure (p=0.017) and MIB-1 LI<2 (p=0.035) had favorable prognosis for PFS and OS. CT, gender, type of surgery, tumor location and tumor diameter did not affect prognosis. In multivariate analysis age, sex, history of seizure, grade and KPS were independent prognostic factors for PFS. Median MIB-1 LI was 2.6 (range, 0.16–54.4) for all patients; 1.0 (range, 0.2–54.4) for grade 2 tumors; and 5.5 for grade 3 tumors (range, 0.16–50). When patients were analyzed separately for OD and OA, MIB-1 LI was found to be a significant prognostic factor for OD (p=0.014), but not for OA histopathology (p=0.266). Conclusions: In OTs MIB-1 LI is demonstrated to be a significant, but not independent prognostic factor for treatment outcomes, in addition to classical prognostic factors for most brain tumors. This significance is prominent in pure ODs and may render being considered in future prospective trials. No significant financial relationships to disclose.
No Surgeon Is an Island
Authors: Maria Chazapis, Suneetha Ramani Moonesinghe
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants
Authors: Nicholas C Grassly, Ira Praharaj, Sudhir Babji, Saravanakumar Puthupalayam Kaliappan, Sidhartha Giri, Srinivasan Venugopal, Edward P K Parker, Asha Abraham, Jayaprakash Muliyil, Sridhar Doss, Uma Raman, Jie Liu, John Victor Peter, Meghana Paranjape, Shalini Jeyapaul, Shailaja Balakumar, Jeniffer Ravikumar, Rajan Srinivasan, Sunil Bahl, Miren Iturriza-Gómara, Holm H Uhlig, Eric R Houpt, Jacob John, Gagandeep Kang
Journal: The Lancet Infectious Diseases (2016)
Trajectory of body shape in early and middle life and all cause and cause specific mortality: results from two prospective US cohort studies
Authors: Mingyang Song, Frank B Hu, Kana Wu, Aviva Must, Andrew T Chan, Walter C Willett, Edward L Giovannucci
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To assess body shape trajectories in early and middle life in relation to risk of mortality. <b>Design</b>&nbsp;Prospective cohort study. <b>Setting</b>&nbsp;Nurses' Health Study and Health Professionals Follow-up Study. <b>Population</b>&nbsp;80 266 women and 36 622 men who recalled their body shape at ages 5, 10, 20, 30, and 40 years and provided body mass index at age 50, followed from age 60 over a median of 15-16 years for death. <b>Main outcome measures</b>&nbsp;All cause and cause specific mortality. <b>Results</b>&nbsp;Using a group based modeling approach, five distinct trajectories of body shape from age 5 to 50 were identified: lean-stable, lean-moderate increase, lean-marked increase, medium-stable/increase, and heavy-stable/increase. The lean-stable group was used as the reference. Among never smokers, the multivariable adjusted hazard ratio for death from any cause was 1.08 (95% confidence interval 1.02 to 1.14) for women and 0.95 (0.88 to 1.03) for men in the lean-moderate increase group, 1.43 (1.33 to 1.54) for women and 1.11 (1.02 to 1.20) for men in the lean-marked increase group, 1.04 (0.97 to 1.12) for women and 1.01 (0.94 to 1.09) for men in the medium-stable/increase group, and 1.64 (1.49 to 1.81) for women and 1.19 (1.08 to 1.32) for men in the heavy-stable/increase group. For cause specific mortality, participants in the heavy-stable/increase group had the highest risk, with a hazard ratio among never smokers of 2.30 (1.88 to 2.81) in women and 1.45 (1.23 to 1.72) in men for cardiovascular disease, 1.37 (1.14 to 1.65) in women and 1.07 (0.89 to 1.30) in men for cancer, and 1.59 (1.38 to 1.82) in women and 1.10 (0.95 to 1.29) in men for other causes. The trajectory-mortality association was generally weaker among ever smokers than among never smokers (for all cause mortality: P for interaction &lt;0.001 in women and 0.06 in men). When participants were classified jointly according to trajectories and history of type 2 diabetes, the increased risk of death associated with heavier body shape trajectories was more pronounced among participants with type 2 diabetes than those without diabetes, and those in the heavy-stable/increase trajectory and with a history of diabetes had the highest risk of death. <b>Conclusions</b>&nbsp;Using the trajectory approach, we found that heavy body shape from age 5 up to 50, especially the increase in middle life, was associated with higher mortality. In contrast, people who maintained a stably lean body shape had the lowest mortality. These results indicate the importance of weight management across the lifespan.
Commentary: The gap between doctors' and patients' perceptions
Authors: Kieran Walsh
Journal: BMJ (2004)

During her husband's consultation Mrs Prior mentioned three symptoms of her own: itching, cystitis, and a rash.1 She mentioned them as a “by the way,” and her general practitioner saw her and did some blood tests. Would you be so patient? Or would you ask her to come back? There is no right answer to this question but, reading between the lines, perhaps the primary purpose of the consultation was to discuss her problems. Respondents on bmj.com thought that this was common and that the reasons for it included not wanting to have to make a separate appointment or to wait and, in some countries, not wanting to have to pay. Maybe she thought her problems were trivial or maybe she was afraid that they were not and wanted to downplay them to herself and her husband and her doctor.

Whatever her reasons, the literature suggests that doctors could be better at finding out why patients come to see them. One study showed that in routine consultations 45% of patient's concerns are not elicited.2 In half of visits the doctor and the patient do not agree on the nature of the presenting problem.2 And doctors often assume that patients' first complaint is their chief one, but in fact the order in which patients present their problems is often unrelated to their clinical importance.3 These are all strong arguments for longer appointment times in primary care.

Readers were also asked what they would tell the patient about the results of her tests. The responses varied: most people said they would tell her that she had abnormal liver function and that she needed further investigations. Some said that they would tell her that she had septicaemia or a bug or something nasty. It is striking that nobody discussed how to tell her this news, how much information to give her, or how much she would be able to take in at this stressful time. Respondents were expansive about the differential diagnosis but clammed up when talking to the patient. Maybe it's not surprising then that, while most patients say they want more information than they receive, doctors vastly overestimate the time they spend on explanation and planning for the future.4,5
Shift of Macrophage Phenotype Due to Cartilage Oligomeric Matrix Protein Deficiency Drives Atherosclerotic Calcification
Authors: Yi Fu, Cheng Gao, Ying Liang, Meili Wang, Yaqian Huang, Wei Ma, Tuoyi Li, Yiting Jia, Fang Yu, Wanlin Zhu, Qinghua Cui, Yanhui Li, Qingbo Xu, Xian Wang, Wei Kong
Journal: Circulation Research (2016)

Intimal calcification is highly correlated with atherosclerotic plaque burden, but the underlying mechanism is poorly understood. We recently reported that cartilage oligomeric matrix protein (COMP), a component of vascular extracellular matrix, is an endogenous inhibitor of vascular smooth muscle cell calcification.To investigate whether COMP affects atherosclerotic calcification.ApoE(-/-)COMP(-/-) mice fed with chow diet for 12 months manifested more extensive atherosclerotic calcification in the innominate arteries than did ApoE(-/-) mice. To investigate which origins of COMP contributed to atherosclerotic calcification, bone marrow transplantation was performed between ApoE(-/-) and ApoE(-/-)COMP(-/-) mice. Enhanced calcification was observed in mice transplanted with ApoE(-/-)COMP(-/-) bone marrow compared with mice transplanted with ApoE(-/-) bone marrow, indicating that bone marrow-derived COMP may play a critical role in atherosclerotic calcification. Furthermore, microarray profiling of wild-type and COMP(-/-) macrophages revealed that COMP-deficient macrophages exerted atherogenic and osteogenic characters. Integrin β3 protein was attenuated in COMP(-/-) macrophages, and overexpression of integrin β3 inhibited the shift of macrophage phenotypes by COMP deficiency. Furthermore, adeno-associated virus 2-integrin β3 infection attenuated atherosclerotic calcification in ApoE(-/-)COMP(-/-) mice. Mechanistically, COMP bound directly to β-tail domain of integrin β3 via its C-terminus, and blocking of the COMP-integrin β3 association by β-tail domain mimicked the COMP deficiency-induced shift in macrophage phenotypes. Similar to COMP deficiency in mice, transduction of adeno-associated virus 2-β-tail domain enhanced atherosclerotic calcification in ApoE(-/-) mice.These results reveal that COMP deficiency acted via integrin β3 to drive macrophages toward the atherogenic and osteogenic phenotype and thereby aggravate atherosclerotic calcification.