tbuckley/cabot-search huggingface dataset:
Triple Receptor–Negative Breast Cancer: The Effect of Race on Response to Primary Systemic Treatment and Survival Outcomes
Authors: Shaheenah Dawood, Kristine Broglio, Shu-Wan Kau, Marjorie C. Green, Sharon H. Giordano, Funda Meric-Bernstam, Thomas A. Buchholz, Constance Albarracin, Wei T. Yang, Bryan T.J. Hennessy, Gabriel N. Hortobagyi, Ana Maria Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2008)

The goal of this study was to describe the effect of race on pathologic complete response (pCR) rates and survival outcomes in women with triple receptor-negative (TN) breast cancers.Four hundred seventy-one patients with TN breast cancer diagnosed between 1996 and 2005 and treated with primary systemic chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axillary lymph nodes. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier product-limit method and compared between groups using the log-rank test. Cox proportional hazards models were fitted for each survival outcome to determine the relationship of patient and tumor variables with outcome.Median follow-up time was 24.5 months. One hundred patients (21.2%) were black, and 371 patients (78.8%) were white/other race. Seventeen percent of black patients (n = 17) and 25.1% of white/other patients (n = 93) achieved a pCR (P = .091). Three-year RFS rates were 68% (95% CI, 56% to 76%) and 62% (95% CI, 57% to 67%) for black and white/other patients, respectively, with no significant difference observed between the two groups (P = .302). Three-year OS was similar for the two racial groups. After controlling for patient and tumor characteristics, race was not significantly associated with RFS (hazard ratio [HR] = 1.08; 95% CI, 0.69 to 1.68; P = .747) or OS (HR = 1.08; 95% CI, 0.69 to 1.68; P = .735) when white/other patients were compared with black patients.Race does not significantly affect pCR rates or survival outcomes in women with TN breast cancer treated in a single institution under the same treatment conditions.
Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year‐old: A study from the acute leukemia working party (<scp>ALWP</scp>) of the <scp>E</scp>uropean group of blood and marrow transplantation (<scp>EBMT</scp>)
Authors: Xavier Poiré, Myriam Labopin, Jan J. Cornelissen, Liisa Volin, Carlos Richard Espiga, J. Hendrik Veelken, Noël Milpied, Jean‐Yves Cahn, Ibrahim Yacoub‐Agha, Gustaaf W. van Imhoff, Mauricette Michallet, Lucienne Michaux, Arnon Nagler, Mohamad Mohty
Journal: American Journal of Hematology (2015)

Acute myeloid leukemia with monosomal karyotype (MK AML) carries a very poor prognosis, even after allogeneic stem cell transplantation (SCT). However, SCT remains the only curative option in this high-risk population. Because myeloablative conditioning regimen (MAC) is associated with less relapse, we hypothesized that more intensive conditioning regimen might be beneficial for MK AML patients. We reviewed 303 patients over age 45 diagnosed with either de novo or secondary MK AML. One hundred and five patients received a MAC and 198 a reduced-intensity conditioning (RIC). The median age at SCT was 57-year-old, significantly lower in the MAC (53-year-old) than in the RIC group (59-year-old). The median follow-up was 42 months (range, 3 - 156 months). The 3-year overall survival (OS), leukemia-free survival (LFS), and relapse rate (RR) were not significantly different between both groups with overall values of 34%, 29%, and 51%, respectively. On the contrary, the 3-year nonrelapse mortality (NRM) was significantly higher in MAC recipients (28%) compared with RIC patients (16%, P = 0.004). The incidence of Grades II to IV acute graft-versus-host disease (GvHD) was significantly higher after a MAC (30.5%) than after a RIC (19.3%, P = 0.02). That of chronic GvHD was comparable between both groups (35%) and did not impact on LFS. Interestingly, within our MK AML cohort, hypodiploidy was significantly associated with worse outcomes. Due to reduced toxicity and comparable OS, LFS, and RR, RIC appears as a good transplant option in the very high-risk population, including older patients, diagnosed with MK AML.
Preparation of endometrium for egg donation
Authors: P Devroey
Journal: Human Reproduction Update (1998)

Nowadays oocyte donation is a well established method of assisted reproduction and offers the unique opportunity to treat patients with various clinical indications, with or without ovarian function, in a novel way. In women with ovarian failure, artificial menstrual cycles are required before proceeding to oocyte donation. Oestrogen may be delivered in the form of oral tablets, transdermal patches in order to bypass the gastrointestinal tract thus avoiding first pass metabolism and by vaginal application. Our regimen is oestradiol valerate given in various concentrations, in order to mimic the regular cyclic fluctuations throughout the cycle. Progesterone may be administered in the form of oral tablets, intravaginal suppositories or rings and i.m. injections. Our results, as of most other groups, strongly support the vaginal route of progesterone administration. In women with retained ovarian function, synchronization of donor-recipient cycle presents a special problem, as there is strong evidence that a temporal window of maximal endometrial receptivity exists. Cryopreservation of donated embryos may be used to overcome the problem, but this approach has the important drawback of embryonic loss occurring after freezing and thawing. The method of choice is the administration of gonadotrophin-releasing hormone agonists (GnRHa) to render the patients functionally agonadal in order to circumvent cycle asynchrony between the donor and recipient.
An osseointegrated human-machine gateway for long-term sensory feedback and motor control of artificial limbs
Authors: Max Ortiz-Catalan, Bo Håkansson, Rickard Brånemark
Journal: Science Translational Medicine (2014)

An osseointegrated interface allowed long-term stable and bidirectional communication between robotic prostheses and implanted neuromuscular electrodes for intuitive control with sensory feedback in one patient.
P235 The Bristol COPD Knowledge Questionnaire (BCKQ): Assessing the Knowledge of Healthcare Professionals Involved in the Delivery of COPD Services
Authors: K Edwards, S Singh
Journal: Thorax (2012)

<h3>Introduction</h3> Healthcare professionals (HCPs) involved in the delivery of COPD services and self-management interventions require appropriate knowledge to inform patients about their condition. Although patient knowledge is often assessed to encourage patient education and self-management, little is done to assess the knowledge of HCPs providing disease information to patients and to establish whether HCPs have a broad spectrum of knowledge to effectively support disease management. <h3>Objective</h3> To assess the knowledge of HCPs involved in the delivery of COPD services. <h3>Method</h3> The Bristol COPD Knowledge Questionnaire (BCKQ) was distributed to 108 HCPs working in primary and secondary care COPD services (Coventry, Leicester, Lothian, Nottingham and Northampton) to assess knowledge. The BCKQ is primarily an outcome measure for patient knowledge (White <i>et al</i>. 2006). It is a multiple choice questionnaire containing 13 topics, each with five statements giving a total of 65 questions for which there is a right or wrong answer. Positive scoring was used with a mark being given for a correct answer. Incorrect responses indicate a knowledge deficit. <h3>Results</h3> The overall findings revealed that HCPs had a mean score of 50 (77%) (minimum 24, maximum 62). The results from the BCKQ revealed particular gaps in knowledge in the breathlessness topic with a mean score of 3.3 (66%) (minimum 1, maximum 5) and across the medication topics, particularly inhaled steroids with only a mean score of 2.7 (54%) (minimum 0, maximum 5) of participants providing correct answers. <h3>Conclusion</h3> The HCPs involved in the delivery of these COPD services had particular gaps in knowledge around breathlessness and medications. HCP gaps in knowledge could inadvertently impact patient knowledge and understanding of their condition and subsequently the ability of patients to effectively self-manage their COPD. Identifying gaps in knowledge can encourage HCP education and training to enhance HCP knowledge and subsequent patient care. White, R. Walker, P. Roberts, S. Kalisky, S and White, P (2006) ‘Bristol COPD Knowledge Questionnaire (BCKQ): testing what we teach patients about COPD’. <i>Chronic Respiratory Disease</i> 3: 123–131.
Chronic lymphocytic leukemia patients with highly stable and indolent disease show distinctive phenotypic and genotypic features
Authors: Anna Guarini, Gianluca Gaidano, Francesca Romana Mauro, Daniela Capello, Francesca Mancini, Maria Stefania De Propris, Marco Mancini, Enrica Orsini, Massimo Gentile, Massimo Breccia, Antonio Cuneo, Gianluigi Castoldi, Robert Foa
Journal: Blood (2003)
Neural and Neurobehavioral Dysfunction in Children with Obstructive Sleep Apnea
Authors: Dean W Beebe
Journal: PLoS Medicine (2006)

Research has confirmed what many parents have long suspected: inadequate sleep in children is associated with daytime behavioral problems and poor academic functioning [1–3]. A fact less well-recognized by clinicians and the general public is that sleep-related breathing disorders, which occur in two to ten percent of children depending on how they are defined, can have a significant impact even among children who have normal sleep duration [4]. Snoring is a hallmark symptom of sleep-disordered breathing, and enlarged tonsils are often a contributing factor to the breathing disturbance. We still do not fully understand the mechanism that links snoring or enlarged tonsils with behavioral problems and poor grades.

One of the more severe nocturnal breathing disorders, obstructive sleep apnea (OSA), involves partial or complete breathing blockage recurrently during sleep, resulting in intermittent drops in blood oxygen levels and probable sleep disruption. Although brain processes are presumed to mediate the link between these medical factors and daytime behavioral and scholastic problems, our understanding of these processes remains fairly theoretical and speculative. The frontal and hippocampal regions of the brain, which are implicated in the regulation of behavior and memory, respectively, appear to be most vulnerable to OSA [4], but the evidence is indirect.

In a new study published in PLoS Medicine, Ann Halbower and colleagues [5] used proton magnetic resonance spectroscopy (MRS), a non-invasive neuroimaging technique that can detect chemical metabolites linked to neural dysfunction, to shed more direct light on the neural functioning of children with OSA.
<i>FGFR1</i> Amplification Drives Endocrine Therapy Resistance and Is a Therapeutic Target in Breast Cancer
Authors: Nicholas Turner, Alex Pearson, Rachel Sharpe, Maryou Lambros, Felipe Geyer, Maria A. Lopez-Garcia, Rachael Natrajan, Caterina Marchio, Elizabeth Iorns, Alan Mackay, Cheryl Gillett, Anita Grigoriadis, Andrew Tutt, Jorge S. Reis-Filho, Alan Ashworth
Journal: Cancer Research (2010)

Amplification of fibroblast growth factor receptor 1 (FGFR1) occurs in approximately 10% of breast cancers and is associated with poor prognosis. However, it is uncertain whether overexpression of FGFR1 is causally linked to the poor prognosis of amplified cancers. Here, we show that FGFR1 overexpression is robustly associated with FGFR1 amplification in two independent series of breast cancers. Breast cancer cell lines with FGFR1 overexpression and amplification show enhanced ligand-dependent signaling, with increased activation of the mitogen-activated protein kinase and phosphoinositide 3-kinase-AKT signaling pathways in response to FGF2, but also show basal ligand-independent signaling, and are dependent on FGFR signaling for anchorage-independent growth. FGFR1-amplified cell lines show resistance to 4-hydroxytamoxifen, which is reversed by small interfering RNA silencing of FGFR1, suggesting that FGFR1 overexpression also promotes endocrine therapy resistance. FGFR1 signaling suppresses progesterone receptor (PR) expression in vitro, and likewise, amplified cancers are frequently PR negative, identifying a potential biomarker for FGFR1 activity. Furthermore, we show that amplified cancers have a high proliferative rate assessed by Ki67 staining and that FGFR1 amplification is found in 16% to 27% of luminal B-type breast cancers. Our data suggest that amplification and overexpression of FGFR1 may be a major contributor to poor prognosis in luminal-type breast cancers, driving anchorage-independent proliferation and endocrine therapy resistance.
John Moore: eighteenth century physician, bearleader and social observer
Authors: A. Steptoe
Journal: Journal of the Royal Society of Medicine (2005)

Many great figures in history began their working lives in medicine but moved away from the profession and excelled in other spheres; the philosopher John Locke, the poet John Keats, and the revolutionary Che Guevara are examples. Another group are those who used their medical training as a passport to a wider world that permitted their talents to flourish outside medicine. One such was John Moore, an eighteenth-century Scottish physician who in middle age seized the opportunity afforded by aristocratic connections to move from a comfortable but mundane medical practice in Glasgow to celebrity as a social observer and novelist.
Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells
Authors: Andrew M. Intlekofer, Naofumi Takemoto, Charlly Kao, Arnob Banerjee, Felix Schambach, John K. Northrop, Hao Shen, E. John Wherry, Steven L. Reiner
Journal: The Journal of Experimental Medicine (2007)

Immunity to intracellular pathogens requires dynamic balance between terminal differentiation of short-lived, cytotoxic effector CD8+ T cells and self-renewal of central–memory CD8+ T cells. We now show that T-bet represses transcription of IL-7Rα and drives differentiation of effector and effector–memory CD8+ T cells at the expense of central–memory cells. We also found T-bet to be overexpressed in CD8+ T cells that differentiated in the absence of CD4+ T cell help, a condition that is associated with defective central–memory formation. Finally, deletion of T-bet corrected the abnormal phenotypic and functional properties of “unhelped” memory CD8+ T cells. T-bet, thus, appears to function as a molecular switch between central– and effector–memory cell differentiation. Antagonism of T-bet may, therefore, represent a novel strategy to offset dysfunctional programming of memory CD8+ T cells.
Plasminogen Activator Inhibitor-1 Is a Significant Determinant of Renal Injury in Experimental Crescentic Glomerulonephritis
Authors: A. Richard Kitching, Yao Z. Kong, Xiao Ru Huang, Piers Davenport, Kristy L. Edgtton, Peter Carmeliet, Stephen R. Holdsworth, Peter G. Tipping
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Crescentic glomerulonephritis is characterized by glomerular fibrin deposition, and experimental crescentic glomerulonephritis has been shown to be fibrin-dependent. Net fibrin deposition is a balance between activation of the coagulation system causing glomerular fibrin deposition and fibrin removal by the plasminogen-plasmin (fibrinolytic) system. Plasminogen activator inhibitor-1 (PAI-1) inhibits fibrinolysis by inhibiting plasminogen activators and has effects on leukocyte recruitment and matrix deposition. To test the hypothesis that the presence of PAI-1 and its levels were a determinant of injury in crescentic glomerulonephritis, accelerated anti-glomerular basement membrane glomerulonephritis was induced in mice genetically deficient in PAI-1 (PAI-1 −/−), PAI-1 heterozygotes (PAI-1 +/−), and mice engineered to overexpress PAI-1 (PAI-1 tg). Compared with strain-matched genetically normal animals, PAI-1 −/− mice with glomerulonephritis developed fewer glomerular crescents, less glomerular fibrin deposition, fewer infiltrating leukocytes, and less renal collagen accumulation at day 14 of disease. The reduction in disease persisted at day 28, when injury had become more established. In contrast, mice overexpressing the PAI-1 gene (PAI-1 tg), that have basal plasma and renal PAI-1 levels several times, normal developed increased glomerular crescent formation, more glomerular fibrin deposition, increased numbers of infiltrating leukocytes, and more renal collagen at both time points. These studies demonstrate that PAI-1 is a determinant of glomerular fibrin deposition and renal injury in crescentic glomerulonephritis. E-mail: [email protected]
Immunological crossreactivity between a cloned antigen of Onchocerca volvulus and a component of the retinal pigment epithelium.
Authors: G Braun, N M McKechnie, V Connor, C E Gilbert, F Engelbrecht, J A Whitworth, D W Taylor
Journal: The Journal of Experimental Medicine (1991)

Onchocerciasis (river blindness) is a major blinding disease in Africa, Central America, and South America. Loss of vision can be due to corneal change, optic atrophy, or chorioretinal disease. It has been suggested that autoimmunological reactions resulting from crossreactivity between parasite antigens and components of eye tissues contribute to development of ocular pathology. Using sera collected from onchocerciasis patients as a screening reagent, a cDNA clone (Ov39) has been isolated from a lambda gt11 expression library of Onchocerca volvulus. This antigen exhibits immunological crossreactivity with a component of retinal pigment epithelium cells (RPE). Antiserum raised against this recombinant peptide immunoprecipitates a 22,000 Mr antigen of adult O. volvulus and recognizes a 44,000 Mr component of bovine RPE by Western blotting. A 44,000 Mr antigen of cultured human RPE metabolically labeled with 35S-methionine can be immunoprecipitated with the same antiserum. An antigen of the same size is recognized by a rabbit antiserum raised against whole O. volvulus extract. Immunocytochemical studies on cryostat sections of the bovine eye using the antirecombinant sera localizes this antigen to the RPE.
Cortical Folding: When, Where, How, and Why?
Authors: Georg F. Striedter, Shyam Srinivasan, Edwin S. Monuki
Journal: Annual Review of Neuroscience (2015)

Why the cerebral cortex folds in some mammals but not in others has long fascinated and mystified neurobiologists. Over the past century—especially the past decade—researchers have used theory and experiment to support different folding mechanisms such as tissue buckling from mechanical stress, axon tethering, localized proliferation, and external constraints. In this review, we synthesize these mechanisms into a unifying framework and introduce a hitherto unappreciated mechanism, the radial intercalation of new neurons at the top of the cortical plate, as a likely proximate force for tangential expansion that then leads to cortical folding. The interplay between radial intercalation and various biasing factors, such as local variations in proliferation rate and connectivity, can explain the formation of both random and stereotypically positioned folds.
Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial
Authors: I. t. investigators
Journal: BMJ (2014)

<b>Objective</b> To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm. <b>Design </b>Randomised controlled trial. <b>Setting</b> 30 vascular centres (29 UK, 1 Canadian), 2009-13. <b>Participants</b> 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm. <b>Interventions</b> 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures). <b>Main outcome measures</b> 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes. <b>Results</b> 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) <i>v</i> 141/183 (77%); P&lt;0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420; $1939) (95% confidence interval −£625 to £2997). <b>Conclusions</b> A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women. <b>Trial registration</b> Current Controlled Trials ISRCTN48334791.
Surgical treatment of dislocations of the acromioclavicular joint in the athlete.
Authors: M Krueger-Franke, C H Siebert, B Rosemeyer
Journal: British Journal of Sports Medicine (1993)

The treatment of the sports related dislocation of the acromioclavicular joint remains controversial. This study was carried out to determine whether or not a combined surgical procedure consisting of repair and polydioxanone (PDS)-cord augmentation of the coracoclavicular ligaments, fixation of the acromioclavicular joint with a single Kirschner wire as well as the repair of the acromioclavicular ligament permitted return to athletic activity. Athletes were examined with regard to their range of motion, pain and their ability to return to the performance level achieved before the injury. During the period 1986-1989, 21 athletes were treated. Follow-up averaged 22 months. Return of athletes to previous performance level was related to their original degree of activity. Two recreational once-a-week athletes did not return to this level, 19 patients, including five competitive athletes, continued their previous activities. There was no correlation between coracoclavicular ossification or post-traumatic arthritis and a good or excellent result. We recommend the operative treatment of acromioclavicular separations in athletes.