tbuckley/cabot-search huggingface dataset:
Expression of erythropoietin receptors by plasma cells from patients with multiple myeloma: Potential relevance to pharmacological use of erythropoietin.
Authors: P. S. Becker, C. P. Miller, B. L. Wood, S. Chien, W. Bensinger, F. Shahijanian, C. A. Blau
Journal: Journal of Clinical Oncology (2010)

8124 Background: Three quarters of multiple myeloma patients (pts) present with anemia at diagnosis, and at least 1/3 have renal insufficiency. Over the course of the disease, many develop renal failure and even require hemodialysis. One consequence of renal dysfunction is deficient erythropoietin production. However, with recent demonstration of clinical trials that exhibit cancer progression and reduced survival for pts treated with erythropoiesis-stimulating agents (ESAs), clinicians face a difficult decision with consideration of relative risk to benefit to optimize management of anemia in these pts. Methods: We have studied expression of erythropoietin receptors (EpoRs) by non-erythroid cancer cell lines and primary myeloma cells from 32 pt diagnostic bone marrow specimens by multicolor flow cytometry using antibodies to CD45, CD38, CD56 and CD138 and murine monoclonal antibody to the extracellular domain of the EpoR. Signal transduction through the EpoR was examined by intracellular flow cytometry and nanofluidic proteomic assay of CD138 positive plasma cells isolated by the MACS magnetic device. Results: Of non-erythroid cell lines, the highest expression of EpoR was noted among the myeloma cell lines. Examination of primary myeloma pt marrows by multicolor flow cytometry demonstrated EpoR expression by gated myeloma cells for 40% of the 32 pt samples examined. The corresponding lymphocytes from the same pts did not exhibit EpoR expression by flow cytometry, so such expression was not a feature of the entire lymphoid-plasma cell lineage. Signal transduction through the EpoR was demonstrated for the U266 myeloma cell line by flow cytometry for intracellular expression of pSTAT5 and pERK1/2. Nanofluidic proteomic assay confirmed phosphorylation of STAT5 and ERK1/2 in the U266 cell line 5 minutes after Epo stimulation, and similar studies are underway for primary pt myeloma cells. Expression studies are also in progress for bone marrow cells from other hematological malignancies and normal bone marrow specimens. Conclusions: These studies may elucidate mechanisms for the tumor progression associated with ESA administration in cancer patients. No significant financial relationships to disclose.
Some breast cancer patients with low genetic risk may not need chemotherapy, trial shows
Authors: Susan Mayor
Journal: BMJ (2016)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Some breast cancer patients with low genetic risk may not need chemotherapy, trial shows Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Clinical Significance of Serum Soluble CD Molecules to Assess Disease Activity in Vitiligo
Authors: Reinhart Speeckaert, Jo Lambert, Nanja van Geel
Journal: JAMA Dermatology (2016)

It is difficult to determine disease activity in vitiligo owing to the absence of inflammatory signs, such as erythema or scaling. A biomarker that could confirm active disease and indicate likely future disease progression would therefore be of considerable value.To investigate whether soluble CD27 (sCD27), sCD25, or sCD40L could be valuable biomarkers to determine disease activity in vitiligo and indicate likely future progression.A combined cross-sectional and prospective study was conducted at the department of dermatology at Ghent University Hospital between February 24, 2012, and December 12, 2015. Ninety-three patients with vitiligo were enrolled, including 83 individuals with nonsegmental vitiligo and 10 with segmental vitiligo. Blood sampling was performed, and sCD25, sCD27, and sCD40L were measured in serum.The associations between sCD levels, disease activity, and future progression were investigated.Of the 93 patients included in the study, 51 were women (55%); median (interquartile range) age was 36.5 (26.0-49.8) years. Both sCD27 (21.5 ng/mL [16.1-30.0 ng/mL] vs 18.4 ng/mL [12.5-22.1 ng/mL]; P = .006) and sCD25 (2.6 ng/mL [2.1-3.4 ng/mL] vs 2.2 ng/mL [1.7-2.4 ng/mL]; P = .002) levels were associated with active disease. Moreover, a statistically significant link with disease progression after 3 to 6 months was found for sCD27 (21.7 [17.0-29.1] vs 16.6 [13.5-23.7]; P = .02) but not for sCD25 (2.8 ng/mL [2.2-3.4 ng/mL] vs 2.3 [1.9-2.8 ng/mL]; P = .053). Further in vitro experiments showed a correlation between sCD25 and interferon γ (r = 0.562, P = .005), interleukin 10 (r = 0.453, P = .03), and sCD27 secretion (r = 0.549, P = .007). No associations were found for sCD40L levels.This study demonstrates increased levels of sCD27 and sCD25 in patients with active vitiligo. Moreover, these results provide the first evidence that these markers have a capacity to indicate the probability of future disease progression, which supports their role as biomarkers in vitiligo.
Safety and antitumor activity of the PARP inhibitor BMN673 in a phase 1 trial recruiting metastatic small-cell lung cancer (SCLC) and germline BRCA-mutation carrier cancer patients.
Authors: Zev A. Wainberg, Saeed Rafii, Ramesh K. Ramanathan, Lida A. Mina, Lauren Averett Byers, Rashmi Chugh, Jonathan Wade Goldman, Jasgit C. Sachdev, Daniela E. Matei, Jennifer J. Wheler, Joshua W. Henshaw, Charlie Zhang, Gilles Gallant, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2014)

7522 Background: BMN 673 is the most potent inhibitor of PARP1/2 in clinical development (IC50<1nM), inducing synthetic lethality in tumors deficient in homologous recombination. Based on preclinical data showing high PARP expression in SCLC models and significant antitumor activity of BMN 673, an expansion cohort of SCLC patients was also studied. Methods: Safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of BMN 673 were evaluated in a 2-stage study. In dose escalation (Stage 1), cycle 1 was 6 wks, with drug taken on days 1 and 8-35, for PK and PD assays, followed by daily continuous dosing in 4-wk cycles. Stage 2(expansion at MTD) recruited pts with tumors defective in DNA repair: Previously treated extensive stage SCLC (second line), Ewing's sarcoma (ES), or tumors in germline (g) BRCA mutation (mut) carriers. Results: Stage 1: The MTD and Recommended Phase 2 Dose (RP2D) was established at 1 mg/d in 39 pts (33F/6M) treated at doses ranging from 25 to 1100 μg/d. Dose-limiting thrombocytopenia occurred in 1/6 and 2/5 pts at 900 and 1100 μg/d, respectively. Stage 2: To date, 54 pts [38F/16M, median age 52 (range 18-78)] have been enrolled: 15 SCLC, 12 ES and 27 gBRCA mut. RECIST confirmed responses have been reported in 2/11 (18%) evaluable previously treated SCLC pts [Clinical Benefit Rate (PR+SD > 8 wks): 6/11 pts (55%); median PFS: 7.4 wks, 95% CI 4.3-19.4]; 12/26 (46%) gBRCA mut ovarian cancer pts (median PFS: 32.3 wks, 95%CI 28.2-38.6); and 8/18 (44%) gBRCA mut breast cancer pts (median PFS: 31 wks, 95% CI 13.1-45.4). No responses were seen in ES pts. Overall, the most frequent adverse events were mild to moderate and included fatigue (all grades=30%), nausea (26%), alopecia (25%), anemia (23%), thrombocytopenia (20%) and neutropenia (14%). Conclusions: BMN 673 is well tolerated at the RP2D of 1 mg/d. BMN 673 has antitumor activity in pts with advanced previously treated SCLC and significant activity in pts with gBRCA mut ovarian and breast cancer. A phase 3 trial in gBRCA mut breast cancer is ongoing. Clinical trial information: NCT01286987.
Antony Peter Bird
Authors: Christopher Nankivell
Journal: BMJ (2016)

Antony Peter Bird grew up in a vicarage on the banks of the River Severn in Shrewsbury, where his father was parish priest and chaplain to the prison. He had the traditional boy’s boarding school education, where he shone in the arts, not the sciences. He won a classics scholarship to St John’s College, Oxford, and took degrees in classics, philosophy, and theology. He did his national service with the Royal Electrical and Mechanical Engineers and trained for the priesthood at Ripon College Cuddesdon. A curacy in Stafford showed that he was a born parish priest, teacher, preacher, and diligent listener; his house was open to all. This idyll was cut short in 1960 when he was called back to Cuddesdon to train ordinands, working as a vice principal to Robert Runcie (later Archbishop of Canterbury). Then, for reasons not all clear, he moved to Birmingham to read medicine. He had a tough time as an older medical student, married with children and no science background. He qualified in 1970 and joined a general practice at Cotteridge, Kings Norton, in Birmingham. Antony was friendly with several doctors and theologians in Birmingham at …
Expanding Long-term Care Options for Persons With Serious Mental Illness
Authors: Mitchell D. Feldman, Eric A. Feldman, Saul Feldman
Journal: JAMA (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 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
Evaluation of World Rugby's concussion management process: results from Rugby World Cup 2015
Authors: Colin W Fuller, Gordon W Fuller, Simon P T Kemp, Martin Raftery
Journal: British Journal of Sports Medicine (2016)

To evaluate World Rugby's concussion management process during Rugby World Cup (RWC) 2015.A prospective, whole population study.639 international rugby players representing 20 countries.The concussion management process consisted of 3 time-based, multifaceted stages: an initial on-pitch and/or pitch-side assessment of the injury, a follow-up assessment within 3 hours and an assessment at 36-48 hours. The initial on-pitch assessment targeted obvious signs of concussion, which, if identified, lead to a 'permanent removal from play' decision and a diagnosis of concussion. If the on-pitch diagnosis was unclear, a 10-min off-pitch assessment was undertaken for signs and symptoms of concussion leading to a 'suspected concussion with permanent removal from play' or a 'no indication of concussion with return to play' decision. Evaluations at 3 and 36-48 hours postmatch lead to diagnoses of 'confirmed concussion' or 'no concussion'. Medical staff's decision-making was supported during each stage by real-time video review of events. Players diagnosed with confirmed concussion followed a 5-stage graduated-return-to-play protocol before being allowed to return to training and/or competition.Players were evaluated for concussion on 49 occasions, of which 24 resulted in diagnoses of concussion. Fourteen players showing on-pitch signs of concussion were permanently removed from play: 4 of the 5 players removed from play following off-pitch medical room evaluation were later diagnosed with a confirmed concussion. Five players not exhibiting in-match signs or symptoms of concussion were later diagnosed with concussion. The overall incidence of concussion during RWC 2015 was 12.5 concussions/1000 player-match-hours.This study supports the implementation of a multimodal, multitime-based concussion evaluation process to ensure that immediate and late developing concussions are captured.
Long-Term Outcomes of the Ross Procedure Versus Mechanical Aortic Valve Replacement
Authors: Amine Mazine, Tirone E. David, Vivek Rao, Edward J. Hickey, Shakira Christie, Cedric Manlhiot, Maral Ouzounian
Journal: Circulation (2016)

Background: The ideal aortic valve substitute in young and middle-aged adults remains unknown. We sought to compare the long-term outcomes of patients undergoing the Ross procedure and those receiving a mechanical aortic valve replacement (AVR). Methods: From 1990 to 2014, 258 patients underwent a Ross procedure and 1444 had a mechanical AVR at a single institution. Patients were matched into 208 pairs through the use of a propensity score. Mean age was 37.2±10.2 years, and 63% were male. Mean follow-up was 14.2±6.5 years. Results: Overall survival was equivalent (Ross versus AVR: hazard ratio, 0.91, 95% confidence interval, 0.38–2.16; P =0.83), although freedom from cardiac- and valve-related mortality was improved in the Ross group (Ross versus AVR: hazard ratio, 0.22; 95% confidence interval, 0.034–0.86; P =0.03). Freedom from reintervention was equivalent after both procedures (Ross versus AVR: hazard ratio, 1.86; 95% confidence interval, 0.76–4.94; P =0.18). Long-term freedom from stroke or major bleeding was superior after the Ross procedure (Ross versus AVR: hazard ratio, 0.09; 95% confidence interval, 0.02–0.31; P &lt;0.001). Conclusions: Long-term survival and freedom from reintervention were comparable between the Ross procedure and mechanical AVR. However, the Ross procedure was associated with improved freedom from cardiac- and valve-related mortality and a significant reduction in the incidence of stroke and major bleeding. In specialized centers, the Ross procedure represents an excellent option and should be considered for young and middle-aged adults undergoing AVR.
A Targeted Functional Clone Tracking Assay for the Identification of Tumour Suppressor Genes in BCP- ALL Implicates the Transcription Factors FOXO3 and PRDM1
Authors: Paul Sinclair, Joanna Cheng, Prahlad Raninga, Rebecca Hanna, Shaun Hollern, Amir Enshaei, Helen Blair, Sirintra Nakjang, Sarra Ryan, Jeyanthy Eswaran, Lars Buechler, Olaf Heidenreich, Christine Harrison
Journal: Blood (2015)
An evolutionary analysis of rules regulating human inbreeding and marriage
Authors: Nancy Wilmsen Thornhill
Journal: Behavioral and Brain Sciences (1991)

Abstract Evolutionary theory predicts that humans should avoid incest because of the negative effects incest has on individual reproduction: production of defective offspring. Selection for the avoidance of close-kin mating has apparently resulted in a psychological mechanism that promotes voluntary incest avoidance. Most human societies are thought to have rules regulating incest. If incest is avoided, why are social rules constructed to regulate it? This target article suggests that incest rules do not exist primarily to regulate close-kin mating but to regulate inbreeding between more distant kin (especially cousin categories) and sexual relations between affinal relatives (often nonkin). Three evolutionary hypotheses about cousin marriage and affinal kin mating follow from this suggestion: (1) Rules regulating mating between affinal kin are means of paternity protection. Cousin marriage (inbreeding) is regulated because, if it occurs, it can concentrate wealth and power within families to the detriment of (2) the powerful positions of rulers in stratified societies and (3) the relatively equal social statuses of most men in egalitarian societies. Tests using the comparative method on a worldwide sample of 129 societies supported the three hypotheses. Two alternative anthropological hypotheses (derived from Freudian theory and alliance theory) failed to be supported.
Position 97 of HLA-B, a residue implicated in pathogenesis of ankylosing spondylitis, plays a key role in cell surface free heavy chain expression
Authors: Liye Chen, Hui Shi, Jack Yuan, Paul Bowness
Journal: Annals of the Rheumatic Diseases (2016)

Association of position 97 (P97) residue polymorphisms in human leucocyte antigen (HLA)-B, including HLA-B*27, with ankylosing spondylitis (AS) has recently been reported. We studied the effect of P97 variations on cell surface expression of the AS-associated HLA-B*27 and HLA-B*51, and the AS-protective HLA-B*7. Flow cytometry was used to measure surface expression of HLA-B*27 in C1R/HeLa cells expressing HLA-B*27 (N97) and six mutants at P97 (N97T, N97S, N97V, N97R, N97W and N97D). Transporter associated with antigen processing-deficient T2, tapasin-deficient 220, β2m-deficient HCT15 and endoplasmic reticulum aminopeptidase 1 or β2m-clustered regularly interspaced short palindromic repeats/Cas9-knockout HeLa cells were used to provide evidence for specific protein interactions. Surface expression of HLA-B*7/HLA-B*51 P97 mutants was also studied. Mutation of HLA-B*27 P97 to the AS risk residue threonine increased cell surface free heavy chain (FHC) expression. Protective residues (serine or valine) and non-AS-associated residues (arginine or tryptophan) did not alter FHC expression. The N97D mutation reduced expression of conventional and FHC forms of HLA-B*27. Differences in FHC expression levels between HLA-B*27, HLA-B*27-N97T and HLA-B*27-N97D were dependent on the presence of functional β2m. HLA-B*7, which has an AS-protective serine at P97, expressed lower levels of FHC than HLA-B*27 or HLA-B*51. Introduction of asparagine at P97 of both HLA-B*7 and HLA-B*51 increased FHC expression. The nature of P97 residue affects surface expression of HLA-B*27, B*7 and B*51, with AS-associated residues giving rise to higher FHC expression levels. The association of P97 amino acid polymorphisms with AS could be, at least in part, explained by its effect on HLA-B*27 FHC cell surface expression.
Chemical gas-generating nanoparticles for tumor-targeted ultrasound imaging and ultrasound-triggered drug delivery
Authors: Hyun Su Min, Sejin Son, Dong Gil You, Tae Woong Lee, Jangwook Lee, Sangmin Lee, Ji Young Yhee, Jaeyoung Lee, Moon Hee Han, Jae Hyung Park, Sun Hwa Kim, Kuiwon Choi, Kinam Park, Kwangmeyung Kim, Ick Chan Kwon
Journal: Biomaterials (2016)
15-year survival outcomes following primary androgen deprivation therapy for localized prostate cancer.
Authors: Grace L. Lu-Yao, Peter C. Albertsen, Dirk Moore, Weichung Shih, Yong Lin, Robert S. DiPaola, Siu-Long Yao
Journal: Journal of Clinical Oncology (2014)

5033 Background: Primary androgen deprivation therapy (ADT) for early stage prostate cancer has been widely utilized for localized prostate cancer, especially among older patients, despite a lack of data supporting its use. This study presents long-term survival outcomes following primary ADT in older men with localized (T1/T2) prostate cancer as a follow up to our prior study. Methods: Instrumental variable analysis was used to assess the impact of primary ADT in a population-based cohort consisting of residents in areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program. Results: The cohort consisted of 66,717 patients aged ≥66 years diagnosed in 1992-2009 who received no definitive local therapy within 180 days of prostate cancer diagnosis. After a median follow-up of 9.2 years, primary ADT was not associated with improved 15-year overall or prostate cancer-specific survival. Among patients with moderately differentiated cancers, 15-year overall survival was 20.0% in high-use regions vs. 20.8% in low-use regions (difference 95% CI -2.2% to 0.4%), and 15-year prostate cancer survival was 90.6% in both high- and low- use regions (difference 95% CI -1.1% to 1.2%). Among patients with poorly differentiated cancers, the 15-year cancer-specific survival was 78.6% in high-use regions versus 78.5%, in low-use regions (difference 95% CI -1.8% to 2.4%), and 15-year overall survival was 8.6% in high-use regions vs. 9.2% in low-use regions (difference 95% CI -1.5% to 0.4%). Conclusions: Primary ADT is not associated with improved long-term overall or disease-specific survival for localized prostate cancer.
Prognostic value of circulating tumor cells in advanced gastroesophageal adenocarcinomas in the randomized trial PRODIGE 17- MEGA (Unicancer GI-AGEO).
Authors: Simon Pernot, Cecile Badoual, Magali Terme, Florence Castan, Elie Marcheteau, Olivier Bouche, Jaafar Bennouna, Eric Francois, Francois Ghiringhelli, Christelle De La Fouchardiere, Emmanuelle Samalin, Jean Baptiste Bachet, Christophe Borg, Michel Ducreux, Aurelie Cazes, Trevor Stanbury, Sophie Gourgou, David Malka, Julien Taieb
Journal: Journal of Clinical Oncology (2016)

4030 Background: Circulating tumor cells (CTC) with CellSearch Veridex, is a prognostic marker in breast, colon and prostate cancer approved by the Food and Drug Administration but is not validated in gastroesophageal adenocarcinomas (GEA). Objective: To evaluate the prognostic value of CTC in advanced GEA before and during treatment (Tx). Methods: 134 patients (pts) were enrolled in the biological substudy of the randomized trial PRODIGE 17 ACCORD 20 MEGA testing FOLFOX +/- panitumumab or rilotumumab in 1st-line Tx of locally advanced or metastatic GEA. Blood samples were collected on CellSave tubes on day (D)0 and D28, after 2 cycles. CTC were detected with CellSearch Veridex. Prognostic value of CTC was analyzed using the Cox model. Results: Quantification of CTC at D0 and D28 was achieved for respectively 106 and 65 pts. The median of CTC at D0 was 1 [range: 0-415], with 40 (38%), 17 (16%), 10 (9%), and 39 (37%) pts with 0, 1, 2, or > 2 CTC, respectively. A CTC level at D0 ≥ 2 was significantly associated with worse PFS and OS. The number of CTC decreased under Tx regardless of Tx arm (p < 0.001). The persistence of CTC ≥ 2 at D28 was associated with even poorer PFS and OS as compared to D0. After adjustment on tumor location, histological type (diffuse vs intestinal), age, ECOG PS and the number of metastases (1 vs > 1), CTC ≥ 2 at D0 remained an independent prognostic factor for PFS (HR: 1.71; 95%CI, 1.06-2.77; p = 0.03) and OS (HR: 2.03; 95%CI, 1.19-3.48; p = 0.01). No interaction was found between CTC and Tx received. Conclusions: Quantification of CTC before Tx could be a useful prognostic tool in advanced GEA. A CTC threshold ≥ 2 seems to have better discriminant value than the presence or absence of CTC. CTC quantitation at D28 may help to adapt Tx early in non-responding pts. Clinical trial information: NCT01443065.CTC pts (%) PFS (months) HR [IC95] p-value OS (months) HR [IC95] p-value D0 CTC - 40 (38%) 7,8 17,1 CTC + 66 (62%) 5,9 1,67 [1,06-2,61] 0,02 11,5 1,80 [1,09-2,95] 0,02 CTC 0-1 57 (54%) 7,6 16,9 CTC ≥ 2 49 (46%) 5,6 1,59 [1,04-2,43] 0,03 11,1 1,85 [1,17-2,92] 0,01 D28 CTC - 45 69%) 8,3 17,4 CTC + 20 (31%) 5,1 1,90 [1,08-3,36] 0,03 11,1 1,24 [0,66-2,35] 0,51 CTC 0-1 53 (82%) 8,3 17,9 CTC ≥ 2 12 (18%) 2,9 4,79 [2,38-9,67] 0,0001 5,4 3,13 [1,55-6,33] 0,004