tbuckley/cabot-search huggingface dataset:
Fatigue and Relating Factors in High-Risk Breast Cancer Patients Treated With Adjuvant Standard or High-Dose Chemotherapy: A Longitudinal Study
Authors: Peter Nieboer, Ciska Buijs, Sjoerd Rodenhuis, Caroline Seynaeve, Louk V.A.M. Beex, Elsken van der Wall, Dick J. Richel, Marianne A. Nooij, Emile E. Voest, Pierre Hupperets, Nanno H. Mulder, Winette T.A. van der Graaf, Els M. TenVergert, Harm van Tinteren, Elisabeth G.E. de Vries
Journal: Journal of Clinical Oncology (2005)

Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.Eight hundred eighty-five patients were randomly assigned between two chemotherapy regimens both followed by radiotherapy and tamoxifen. Fatigue was assessed using vitality scale (score < or = 46 defined as fatigue), poor mental health using mental health scale (score < or = 56 defined as poor mental health) both of Short-Form 36, muscle and joint pain with Rotterdam Symptom Checklist, and Hb levels were assessed before and 1, 2, and 3 years after chemotherapy.Fatigue was reported in 20% of 430 assessable patients (202 standard-dose, 228 high-dose) with at least a 3-year follow-up, without change over time or difference between treatment arms. Mean Hb levels were lower following high-dose chemotherapy. Only 5% of patients experienced fatigue and anemia. Mental health score was the strongest fatigue predictor at all assessment moments. Menopausal status had no effect on fatigue. Linear mixed effect models showed that the higher the Hb level (P = .0006) and mental health score (P < .0001), the less fatigue was experienced. Joint (P < .0001) and muscle pain (P = .0283) were associated with more fatigue.In 3 years after treatment, no significant differences in fatigue were found between standard and high-dose chemotherapy. Fatigue did not change over time. The strongest fatigue predictor was poor mental health.
What Constitutes Optimal Care for Older Women With Breast Cancer?
Authors: Rebecca A. Silliman
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.05.083 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12913101 What Constitutes Optimal Care for Older Women With Breast Cancer? Rebecca A. SillimanxRebecca A. SillimanSearch for articles by this author Show More Department of Medicine, Boston University School of Medicine, Department of Epidemiology, Boston University School of Public Health, Boston, MA https://doi.org/10.1200/JCO.2003.05.083 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Extended Out-of-Hospital Low-Molecular-Weight Heparin Prophylaxis against Deep Venous Thrombosis in Patients after Elective Hip Arthroplasty
Authors: Russell D. Hull, Graham F. Pineo, Paul D. Stein, Andrew F. Mah, Susan M. MacIsaac, Ola E. Dahl, Matthew Butcher, Rollin F. Brant, William A. Ghali, David Bergqvist, Gary E. Raskob
Journal: Annals of Internal Medicine (2001)

Evidence-based medicine guidelines based on venographic end points recommend in-hospital prophylaxis with low-molecular-weight heparin (LMWH) in patients having elective hip surgery. Emerging data suggest that out-of-hospital use may offer additional protection; however, uncertainty remains about the risk-benefit ratio. To provide clinicians with a practical pathway for translating clinical research into practice, we systematically reviewed trials comparing extended out-of-hospital LMWH prophylaxis versus placebo.Studies were identified by 1) searching PubMed, MEDLINE, and the Cochrane Library Database for reports published from January 1976 to May 2001; 2) reviewing references from retrieved articles; 3) scanning abstracts from conference proceedings; and 4) contacting pharmaceutical companies and investigators of the original reports.Randomized, controlled trials comparing extended out-of-hospital prophylaxis with LMWH versus placebo in patients having elective hip arthroplasty.Two reviewers extracted data independently. Reviewers evaluated study quality by using a validated four-item instrument.Six of seven original articles met the defined inclusion criteria. The included studies were double-blind trials that used proper randomization procedures. Compared with placebo, extended out-of-hospital prophylaxis decreased the frequency of all episodes of deep venous thrombosis (placebo rate, 150 of 666 patients [22.5%]; relative risk, 0.41 [95% CI, 0.32 to 0.54; P < 0.001]), proximal venous thrombosis (placebo rate, 76 of 678 patients [11.2%]; relative risk, 0.31 [CI, 0.20 to 0.47; P < 0.001]), and symptomatic venous thromboembolism (placebo rate, 36 of 862 patients [4.2%]; relative risk, 0.36 [CI, 0.20 to 0.67; P = 0.001]). Major bleeding was rare, occurring in only one patient in the placebo group.Extended LMWH prophylaxis showed consistent effectiveness and safety in the trials (regardless of study variations in clinical practice and length of hospital stay) for venographic deep venous thrombosis and symptomatic venous thromboembolism. The aggregate findings support the need for extended out-of-hospital prophylaxis in patients undergoing hip arthroplasty surgery.
Thrombus formation induced by antibodies to β2-glycoprotein I is complement dependent and requires a priming factor
Authors: Fabio Fischetti, Paolo Durigutto, Valentina Pellis, Alessandra Debeus, Paolo Macor, Roberta Bulla, Fleur Bossi, Federica Ziller, Daniele Sblattero, Pierluigi Meroni, Francesco Tedesco
Journal: Blood (2005)
Roointon Faridoon Boomla
Authors: K. B. S. Boomla
Journal: BMJ (2014)

Roointon Faridoon Boomla (“Rooin”) was born in Bombay, the eldest son of a Parsee GP, and came to the UK at the age of 10 when his father decided to emigrate here.

He trained at Barts and qualified in the middle of the war. He had planned to return to India after qualifying to join the fight for Indian independence, but the premature death of his father changed his life plans. He had to take over and run the family practice in Plumstead and see his younger brother through school.

Eventually he was conscripted and posted to Burma in …
Biomarkers in the Prevention and Treatment of Atherosclerosis: Need, Validation, and Future
Authors: James H. Revkin, Charles L. Shear, Hubert G. Pouleur, Steven W. Ryder, David G. Orloff
Journal: Pharmacological Reviews (2007)

Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in the developed world, and there is a clear need to develop novel therapeutic strategies to reduce cardiovascular risk further than is currently possible. Traditionally, the effectiveness of new cardiovascular drugs has been evaluated in clinical trials using cardiovascular outcomes as endpoints. However, such trials require large numbers of patients followed over long periods of time. Clinical trials using surrogate markers for CVD may be shorter in duration and involve fewer participants. Measurement of atherosclerotic progression is an ideal surrogate marker as it is predictive of future cardiovascular events. The "gold standard" for detecting and defining the severity, extent, and rate of atherosclerotic progression has been quantitative coronary angiography. However, this technique has fundamental limitations. More recently, measurement of carotid intima-media thickness using B-mode ultrasound and measurement of atheroma volume using intravascular ultrasound have emerged as more accurate techniques for detecting atherosclerotic progression. Both of these techniques have potential utility as surrogate endpoints in place of cardiovascular outcomes in clinical trials. Their use might facilitate the more rapid development of novel, safe, and effective therapies.
Tenure as a necessary but not sufficient requirement for academic freedom
Authors: John Ruscio, April Kelly-Woessner
Journal: Behavioral and Brain Sciences (2006)

Although the job security afforded by tenure is one important factor in deciding whether or how to exercise academic freedom, professors must weigh a number of other important career goals that constrain their choices. This multiplicity of goals, combined with concerns about career mobility, may help to explain the differences Ceci et al. observe between professors at different ranks.
Relationship Between Type of Insurance and Care During the Early Course of Psychosis
Authors: Jonathan Rabinowitz, Evelyn J. Bromet, Janet Lavelle, Kimberly J. Severance, Sharon L. Zariello, Bruce Rosen
Journal: American Journal of Psychiatry (1998)

Little is known about the relationship between insurance and care in the early course of psychosis. This study explored the insurance status of first-admission psychotic patients and the relationship between type of insurance and care received up to this admission.Data are from the Suffolk County Mental Health Project, an epidemiologic study of first-admission psychosis. Data on insurance status (N=525) were pooled from hospital records, respondents, and significant others. Logistic regression analysis, controlling for key background variables and diagnosis, was used to study the relationship between insurance and care.At first admission, 233 (44%) of the patients had no insurance, 78 (15%) had Medicaid or Medicare, 203 (39%) had private insurance, eight (1.5%) were insured by the Veterans Administration, and the insurance status of three (1.5%) was unknown. Having private insurance increased the likelihood of having received previous mental health treatment (psychotherapy specifically), being admitted voluntarily, being hospitalized in a community hospital rather than a public hospital, and being hospitalized within 3 months of onset of psychosis. Having Medicaid/Medicare increased the likelihood of receiving nonantipsychotic medication before this hospitalization, admission to a community hospital rather than a public hospital, having received previous mental health treatment in general, and voluntary admission.During the early course of psychotic illness, many people lack any type of health insurance, and this is associated with a decreased likelihood of obtaining care before their first hospital admission.
A Novel Human AlkB Homologue, ALKBH8, Contributes to Human Bladder Cancer Progression
Authors: Keiji Shimada, Mitsutoshi Nakamura, Satoshi Anai, Marco De Velasco, Motoyoshi Tanaka, Kazutake Tsujikawa, Yukiteru Ouji, Noboru Konishi
Journal: Cancer Research (2009)

Abstract We recently identified a novel human AlkB homologue, ALKBH8, which is expressed in various types of human cancers including human urothelial carcinomas. In examining the role and function of ALKBH8 in human bladder cancer development in vitro, we found that silencing of ALKBH8 through small interfering RNA transfection reduced reactive oxygen species (ROS) production via down-regulation of NAD(P)H oxidase-1 (NOX-1) and induced apoptosis through subsequent activation of c-jun NH2-terminal kinase (JNK) and p38. However, we also found that JNK and p38 activation resulted in phosphorylation of H2AX (γH2AX), a variant of mammalian histone H2A, which contributes to the apoptosis induced by silencing ALKBH8 and NOX-1. Silencing of ALKBH8 significantly suppressed invasion, angiogenesis, and growth of bladder cancers in vivo as assessed both in the chorioallantoic membrane assay and in an orthotopic mouse model using green fluorescent protein–labeled KU7 human urothelial carcinoma cells. Immunohistochemical examination showed high expression of ALKBH8 and NOX-1 proteins in high-grade, superficially and deeply invasive carcinomas (pT1 and &amp;gt;pT2) as well as in carcinoma in situ, but not in low-grade and noninvasive phenotypes (pTa). These findings indicate an essential role for ALKBH8 in urothelial carcinoma cell survival mediated by NOX-1–dependent ROS signals, further suggesting new therapeutic strategies in human bladder cancer by inducing JNK/p38/γH2AX–mediated cell death by silencing of ALKBH8. [Cancer Res 2009;69(7):3157–64]
Altered regulation of insulin signaling components in adipocytes of insulin-resistant type II diabetic goto-kakizaki rats
Authors: Najman Begum, Louis Ragolia
Journal: Metabolism (1998)

We investigated the cellular mechanism(s) of insulin resistance associated with non—insulin-dependent diabetes mellitus (NIDDM) using adipocytes isolated from non-obese, insulin-resistant type II diabetic Goto-Kakizaki (GK) rats, a well-known genetic rat model for type II diabetic humans. In adipocytes isolated from control rats, insulin (5 nmol/L) stimulated particulate serine/threonine protein phosphatase-1 (PP-1) activity (56% increase over the basal value after 5 minutes). In contrast, adipocytes from diabetic GK rats exhibited a 32% decrease in basal (P < .05) and a 65% decrease in insulin-stimulated PP-1 activity compared with values in control Wistar rats. Conversely, cytosolic PP-2A activity was elevated in diabetic GK rats in the basal state (twofold increase v controls, P < .05). Insulin treatment resulted in a 50% to 60% inhibition in PP-2A activity in control rats, but failed to inhibit PP-2A activity in diabetic GK rat adipocytes. The defects in activation/inactivation were accompanied by inhibition of insulin's effect on mitogen-activated protein kinase (MAPK) activation. In addition, insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) substrate-1- (IRS-1) was decreased more than 90% compared with control values, while a twofold increase in basal IRS-1 phosphorylation status was observed in diabetic GK rats. The abnormalities in IRS-1 phosphorylation were accompanied by a severe impairment of insulin-mediated targeting of the Grb2/Sos complex to the plasma membrane. We conclude that (1) a rapid activation of PP-1 along with concomitant inhibition of cytosolic PP-2A may be important in the mechanism of insulin action in a normal cell, and (2) the resistance to insulin in terms of glucose uptake and glycogen synthesis observed in diabetic GK rats is partly due to defective regulation of PP-1, PP-2A, and MAPK caused by multiple defects in the upstream insulin signaling components (IRS-1/phosphatidylinositol-3-kinase [PI3-kinase] and Grb2/Sos) that participate in insulin-mediated activation of PP-1 and inactivation of PP-2A.
Randomized, Phase III Study of Weekly Paclitaxel in Combination With Carboplatin Versus Standard Every-3-Weeks Administration of Carboplatin and Paclitaxel for Patients With Previously Untreated Advanced Non–Small-Cell Lung Cancer
Authors: Chandra P. Belani, Suresh Ramalingam, Michael C. Perry, Renato V. LaRocca, David Rinaldi, Preston S. Gable, William J. Tester
Journal: Journal of Clinical Oncology (2008)

To compare the efficacy and safety of weekly paclitaxel in combination with carboplatin administered every 4 weeks to the standard regimen of paclitaxel and carboplatin administered every 3 weeks for the treatment of patients with advanced non-small-cell lung cancer (NSCLC).Four hundred forty-four patients with previously untreated stage IIIB/IV NSCLC were randomly assigned to either arm 1 (n = 223), paclitaxel 100 mg/m(2) weekly for 3 of 4 weeks with carboplatin area under the curve (AUC) = 6 mg/mL x min on day 1 of each 4 week cycle, or arm 2 (n = 221), paclitaxel 225 mg/m(2) and carboplatin AUC = 6 on day 1 of each 3-week cycle. After four cycles of therapy, patients in both treatment arms were eligible to continue weekly paclitaxel (70 mg/m(2), 3 of 4 weeks) as maintenance therapy until unacceptable toxicity or disease progression.The objective response rate was 27.6% for arm 1 and 19.2% for arm 2. Median time to progression (TTP) was 18.4 and median survival (MS) was 38.6 weeks for arm 1. For arm 2, the median TTP and MS were 16.7 weeks and 42.9 weeks respectively. Grade 3/4 anemia was more common with arm 1, although grade 2/3 neuropathy and arthralgia were less common. The remainder of the toxicities were similar between the two arms.All efficacy parameters were similar between the two treatment arms. The favorable nonhematologic toxicity profile of arm 1 makes this an alternative treatment option for patients with advanced NSCLC.
Risk and causes of paediatric hospital-acquired bacteraemia in Kilifi District Hospital, Kenya: a prospective cohort study
Authors: Alexander M Aiken, Neema Mturi, Patricia Njuguna, Shebe Mohammed, James A Berkley, Isaiah Mwangi, Salim Mwarumba, Barnes S Kitsao, Brett S Lowe, Susan C Morpeth, Andrew J Hall, Iqbal Khandawalla, J Anthony G Scott
Journal: The Lancet (2011)
Splicing Factor Tra2-β1 Is Specifically Induced in Breast Cancer and Regulates Alternative Splicing of the<i>CD44</i>Gene
Authors: Dirk O. Watermann, Yesheng Tang, Axel zur Hausen, Markus Jäger, Stefan Stamm, Elmar Stickeler
Journal: Cancer Research (2006)

Abstract The human CD44 gene undergoes extensive alternative splicing of multiple variable exons positioned in a cassette in the middle of the gene. Expression of alternative exons is often restricted to certain tissues and could be associated with tumor progression and metastasis of several human malignancies, including breast cancer. Exon v4 contains multiple copies of a C/A-rich exon enhancer sequence required for optimal inclusion of the exon and binding to the nucleic acid–binding proteins YB-1 and human Tra2-β1. Here, we show that hTra2-β1, a member of the extended family of serine/arginine-rich (SR) splicing factors, enhances the in vivo inclusion of CD44 exons v4 and v5. It increased inclusion of exons v4 and v5 and acted synergistically with YB-1. Activation required the C/A-rich enhancer within exon v4. Several other SR proteins had none or only a slight effect on CD44 exon inclusion. In contrast, SC35 inhibited exon usage and antagonized the effects of Tra2 or YB-1. In a matched pair analysis of human breast cancers and their corresponding nonpathologic tissue controls, we found a significant induction of Tra2-β1 in invasive breast cancer, both on the RNA and protein levels. Together with our functional data, these results suggest an important role for Tra2-β1 in breast cancer. Induction of this splicing factor might be responsible for splicing of CD44 isoforms associated with tumor progression and metastasis. (Cancer Res 2006; 66(9): 4774-80)
The Relationship Between Personality Disorders and Axis I Psychopathology: Deconstructing Comorbidity
Authors: Paul S. Links, Rahel Eynan
Journal: Annual Review of Clinical Psychology (2012)

The purpose of this review is (a) to study and systematically review the recent literature examining the co-occurrence and relationships between Axis I psychiatric disorders and Axis II personality disorders, specifically the six originally proposed for the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5, and (b) to consider the clinical utility of the current Axis I and Axis II approach in the DSM-IV-TR and apply findings to state a position on the issue of collapsing together Axis I and Axis II. Community surveys or prospective cohort studies were reviewed as a priority. Our review indicates that the associations between clinical disorders and personality disorders clearly varied within each disorder and across the six personality disorders. Our understanding has advanced, particularly related to the clinical utility of comorbidity, and there may be sufficient evidence to support moving borderline personality disorder to Axis I. However, it seems premature to conclude that comorbidity is best conceptualized by having all disorders in a single category or by deleting disorders so that comorbidity is reduced. Our review suggests some priorities for future research into comorbidity, such as including personality disorders in future multivariate comorbidity models.
Multigene Panel Testing in Oncology Practice
Authors: Allison W. Kurian, James M. Ford
Journal: JAMA Oncology (2015)

A great success of modern human genetics is the identification of specific genes that, when altered, confer clinically recognized traits, such as cancer susceptibility, and enable predictive genetic testing.In past decades, cost and turn-around time limited cancer genetic risk assessment, and it was rarely feasible to test a patient for more than 1 well-defined condition (eg, hereditary breast ovarian cancer [HBOC] or Lynch syndrome).Transformative sequencing advances now permit massively parallel, rapid analysis of many genes, making the "$1000 genome" an imminent reality.In June 2013, long-term barriers to cancer genetic testing were breached by a remarkable convergence of events: the disclosure of her BRCA1 mutation by the actress Angelina Jolie, which dramatically increased public awareness and demand for genetic testing 1 ; and the US Supreme Court decision against gene patenting, which allowed competition to reduce the price of BRCA1 and BRCA2 (BRCA1/2) testing. 2 Incentives quickly shifted toward sequencing more genes as laboratories competed to offer panels of increasing numbers of genes (from 6 to >100) at decreasing prices.Perhaps because testing costs have fallen so greatly, insurers rarely object to multigene panels as a means of diagnosing recognized syndromes (eg, HBOC) when relevant guidelines are met.However, most payers will not cover more than 1 cancer risk assessment test, creating an incentive to sequence any genes of interest concurrently rather than sequentially.In short, multigene panels have entered the clinic, 3 and there seems little chance of forcing the genie back into the bottle.Fortunately, multigene panels offer significant benefits over sequential single-gene testing.They are cheaper, faster, and more efficient for differential diagnosis.Most important, they may identify deleterious mutations that the pedigree would not suggest, particularly for families with cancer patterns that deviate from recognized syndromes.These advances come with drawbacks, however, related to the lack of a testing track record for many genes on commercially available panels. 4 Panel testing is complicated by 3 levels of uncertainty about mutations in less widely tested genes, regarding (1) the magnitude of cancer risk (penetrance), (2) the anatomical and age-specific scope of cancer risk, and (3) the clinical relevance of missense variants in genes for which the spectrum of normalcy is poorly defined.Variants of uncertain significance (VUS) increase in frequency with the number of genes sequenced, 5 and, if skilled genetic counseling is not provided, this may cause anxiety and unwarranted interventions.Recently, concerns have arisen that technical advances in genomics have outpaced our ability to provide safe, ethical care.When guided by appropriate ex-
Diabetes and tuberculosis: a gathering storm?
Authors: J. Moore-Gillon
Journal: Thorax (2010)

The number of cases of active tuberculosis (TB) continues to rise in the UK and in many other parts of the world.1 2 In analysing the reasons behind this rise, it needs to be kept in mind that only a small proportion of those who become infected with TB will progress to become ill with active TB disease in the weeks and months after infection. They do, however, remain at risk of reactivation of their latent TB infection in the years (and indeed decades) to come. Clearly, a co-existing medical condition which impairs the immune response to the TB bacterium might increase the likelihood of direct progression to active disease shortly after infection, or increase the likelihood of latent TB infection in later life. Co-infection with HIV is a striking example; the relative risk of developing TB in HIV-positive individuals compared with HIV-negative individuals (the incidence rate ratio) is between about 20 and 35.2

In this issue of Thorax , Walker and Unwin ( see page 578 ) consider the impact on numbers of TB cases in England of another increasingly common condition—namely, diabetes mellitus.3 A link has long been suggested, the authors pointing out that combined clinics for those with diabetes and TB were being held more …