tbuckley/cabot-search huggingface dataset:
Outcome of Preventive Surgery and Screening for Breast and Ovarian Cancer in BRCA Mutation Carriers
Authors: L. Scheuer
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To prospectively determine the impact of genetic counseling and testing on risk-reduction strategies and cancer incidence in a cohort of individuals at hereditary risk for breast and ovarian cancer. PATIENTS AND METHODS: Two hundred fifty-one individuals with BRCA mutations were identified at a single comprehensive cancer center from May 1, 1995, through October 31, 2000. Uniform recommendations regarding screening and preventive surgery were provided in the context of genetic counseling. Patients were followed for a mean of 24.8 months (range, 1.6 to 66.0 months) using standardized questionnaires, chart reviews, and contact with primary physicians. RESULTS: Frequency of cancer surveillance by physical examinations and imaging studies increased after genetic counseling and testing. Twenty-one breast, ovarian, primary peritoneal, or fallopian tube cancers were detected after receipt of genetic test results. Among 29 individuals choosing risk-reducing mastectomy after testing, two were found to have occult intraductal breast cancers. Among 90 individuals who underwent risk-reducing salpingo-oophorectomy, one early-stage ovarian neoplasm and one early-stage fallopian tube neoplasm were found. Radiographic or tumor marker–based screening detected six breast cancers, five of which were stage 0/I, one early-stage primary peritoneal cancer, and three stage I or II ovarian cancers. Six additional breast cancers were detected by physical examination between radiographic screening intervals; four of these six tumors were stage I. No stage III or stage IV malignancies were detected after genetic testing. CONCLUSION: This study provides prospective evidence that genetic counseling and testing increased surveillance and led to risk-reducing operations, which resulted in diagnosis of early-stage tumors in patients with BRCA1 and BRCA2 mutations.
Unknown unknowns and lessons from non-operative rehabilitation and return to play of a complete anterior cruciate ligament injury in English Premier League football
Authors: Richard Weiler
Journal: British Journal of Sports Medicine (2015)

An English Premier League (EPL) footballer decides to open-mindedly try, at least initially, non-operative and non-interventional treatment of a complete anterior cruciate ligament (ACL) rupture. At 5 weeks, he feels great and fully trusts his knee, sailing with confidence through every graded progression in his evolving rehabilitation programme. He continues with rehabilitation to full training within 8 weeks of a complete ACL injury.1 Now, almost 24 months later, he is still training and playing full competitive professional football. During 22 months available for team selection, there have been no episodes of instability, no knee pain, no effusions, no soft tissue injuries and no discernible impairment on function. There was no change on clinical ligament tests either. Treatment was entirely non-surgical with no use of needles for aspiration or injection. He remains aware that he is very lucky so far, that he cannot predict what could happen in future, possibly requiring surgery, and he is aware that risk of osteoarthritis is high following ACL injury whether reconstruction has taken place or not.2–4 Before jumping to conclusions, perhaps it is worth reading the full paper at BMJ Case Reports to decide for yourself what you may have done in this situation.1 

It is unusual for elite professional athletes to choose the uncertainty of non-operative treatment for an ACL injury when the quantity of research, and …
Comparison of chlorambucil, azathioprine or cyclophosphamide combined with corticosteroids in the treatment of lupus nephritis
Authors: M.S. SABBOUR, LAILA M. OSMAN
Journal: British Journal of Dermatology (1979)

Journal Article Comparison of chlorambucil, azathioprine or cyclophosphamide combined with corticosteroids in the treatment of lupus nephritis Get access M.S. SABBOUR, M.S. SABBOUR Department of Medicine and Clinical Pathology, Ain‐Shams University, Cairo, Egypt Search for other works by this author on: Oxford Academic Google Scholar LAILA M. OSMAN LAILA M. OSMAN Department of Medicine and Clinical Pathology, Ain‐Shams University, Cairo, Egypt Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 100, Issue 2, 1 February 1979, Pages 113–125, https://doi.org/10.1111/j.1365-2133.1979.tb05548.x Published: 01 February 1979
Promoting Regular Mammography Screening I. A Systematic Assessment of Validity in a Randomized Trial
Authors: D. J. del Junco, S. W. Vernon, S. P. Coan, J. A. Tiro, L. A. Bastian, L. S. Savas, C. A. Perz, D. R. Lairson, W. Chan, C. Warrick, A. McQueen, W. Rakowski
Journal: JNCI Journal of the National Cancer Institute (2008)

Most health promotion trials in cancer screening offer limited evidence of external validity. We assessed internal and external validity in a nationwide, population-based trial of an intervention to promote regular mammography screening. Beginning in September 2000, study candidates age 52 years and older (n = 23000) were randomly selected from the National Registry of Women Veterans and sent an eligibility survey. Consistent with intention-to-treat principles for effectiveness trials, we randomly assigned eligible respondents and nonrespondents to one of five groups. We mailed baseline surveys to groups 1–3 followed by intervention materials of varying personalization to groups 1 and 2. We delayed mailing baseline surveys to two additional control groups to coincide with the mailing of postintervention follow-up surveys to groups 1–3 at year 1 (group 4) and year 2 (group 5). Mammography rates were determined from self-report and Veterans Health Administration records. To assess internal validity, we compared groups on participation and factors associated with mammography screening at each stage. To assess external validity, we compared groups 3, 4, and 5 on mammography rates at the most recent follow-up to detect any cueing effects of prior surveys and at the respective baselines to uncover any secular trends. We also compared nonparticipants with participants on factors associated with mammography screening at the trial's end. We established study eligibility for 21340 (92.8%) of the study candidates. Groups 1–3 were similar throughout the trial in participation and correlates of mammography screening. No statistically significant survey cueing effects or differences between nonparticipants and participants across groups were observed. Mammography screening rates over the 30 months preceding the respective baselines were lower in group 5 (82.3% by self-report) than in groups 1–4 (85.1%, P = .024, group 5 vs groups 1–4 combined), suggesting a decline over time similar to that reported for US women in general. This systematic assessment provides evidence of the trial's internal and external validity and illustrates an approach to evaluating validity that is readily adaptable to future trials of behavioral interventions.
Surrogate endpoints for overall survival in locally advanced head and neck cancer: meta-analyses of individual patient data
Authors: Stefan Michiels, Aurélie Le Maître, Marc Buyse, Tomasz Burzykowski, Emilie Maillard, Jan Bogaerts, Jan B Vermorken, Wilfried Budach, Thomas F Pajak, Kian K Ang, Jean Bourhis, Jean-Pierre Pignon
Journal: The Lancet Oncology (2009)
Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial
Authors: Björn Dahlöf, Peter S Sever, Neil R Poulter, Hans Wedel, D Gareth Beevers, Mark Caulfield, Rory Collins, Sverre E Kjeldsen, Arni Kristinsson, Gordon T McInnes, Jesper Mehlsen, Markku Nieminen, Eoin O'Brien, Jan Östergren
Journal: The Lancet (2005)
Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis
Authors: K. R. Qazi, P. Torregrosa Paredes, B. Dahlberg, J. Grunewald, A. Eklund, S. Gabrielsson
Journal: Thorax (2010)

Sarcoidosis is a systemic disease of unknown aetiology characterised by granuloma formation and the presence of interferon γ (IFNγ)-producing T cells that cause inflammation and tissue damage in multiple organs, especially the lung. Exosomes are nano-sized immunomodulatory vesicles of endosomal origin released from a diverse range of cells and are also found in physiological fluids including bronchoalveolar lavage fluid (BALF) from healthy individuals.To investigate whether exosomes are enriched in the lungs of patients with sarcoidosis compared with healthy individuals and whether they could contribute to pathogenesis.BALF exosomes from patients with sarcoidosis (n=36) and healthy controls (n=14) were compared by electron microscopy, flow cytometry, western blot analysis and mass spectrometry. BALF exosomes were incubated with autologous peripheral blood mononuclear cells (PBMCs) or the human bronchial epithelial cell line 16HBE14o-. Cytokines were measured by ELISPOT and ELISA.BALF from patients with sarcoidosis showed increased levels of exosomes compared with healthy individuals. Exosomes from patients showed significantly higher expression of MHC class I and II, tetraspanins CD9, CD63 and CD81 as well as neuregulin-1, known to be associated with cancer progression. Furthermore, BALF exosomes from patients induced significantly higher IFNγ and interleukin (IL)-13 production in autologous PBMCs compared with healthy individuals and could also stimulate IL-8 production from epithelial cells.The results indicate for the first time a role for exosomes in human lung disease with possible contributions to the initiation and progression of inflammation in sarcoidosis. This suggests that exosomes may be a new potential target for the clinical treatment of lung diseases.
Functional Significance of Zinc-Related Signaling Pathways in Immune Cells
Authors: Hajo Haase, Lothar Rink
Journal: Annual Review of Nutrition (2009)

Recent years have brought a paradigm shift for the role of the essential trace element zinc in immunity. Although its function as a structural component of many enzymes has been known for decades, current experimental evidence points to an additional function of the concentration of free or loosely bound zinc ions as an intracellular signal. The activity of virtually all immune cells is modulated by zinc in vitro and in vivo. In this review, we discuss the interactions of zinc with major signaling pathways that regulate immune cell activity, and the implications of zinc deficiency or supplementation on zinc signaling as the molecular basis for an effect of zinc on immune cell function.
Fruit and Vegetable Intake and Breast Cancer Risk: A Case for Subtype-Specific Risk?
Authors: Cynthia A. Thomson, Patricia A. Thompson
Journal: JNCI Journal of the National Cancer Institute (2013)

In this issue of the Journal, Jung et al. (1) report no overall effect of fruit and vegetable consumption on breast cancer risk among women in the large, long-term Pooling Project of Prospective Studies of Diet and Cancer (Pooling Project). When the authors considered hormone-responsive, estrogen receptor (ER)–positive patients separately from the nonhormonal, ER-negative patients under a hypothesis of separate etiology, a statistically significant protective effect of fruit and vegetable consumption was observed for risk of ER-negative, but not ER-positive breast cancer. Most striking, the authors provide evidence that the protective effect of fruit and vegetable consumption for ER-negative breast cancer, in terms of magnitude and direction, were largely consistent across the 20 pooled studies. With these findings, Jung et al. (1) add to the growing number of studies reporting the differential effect of risk factors, including the classic breast cancer reproductive risk factors such as age of first pregnancy, when breast cancer is considered as separate subgroups such as ER-positive, ER-negative and triple negative breast cancer (2). These studies indicate that considering ER-positive and ER-negative breast cancer as a single disease in diet association studies has likely resulted in an underestimation of risk and a possible failure to detect even modest effects that may modify ER-negative breast cancer risk. These findings support the concept of distinct natural histories of hormone-dependent and hormone-independent tumors, as has been suggested by molecular profiling studies (3) and as heralds back to the findings from the Iowa Women’s Study, which described differences in reproductive factors and risk for ER-positive, progesterone receptor–positive, and ER-negative breast cancers (4).
Cardiac Myosin-Binding Protein C Mutations and Hypertrophic Cardiomyopathy
Authors: Sabine J. van Dijk, Dennis Dooijes, Cris dos Remedios, Michelle Michels, Jos M.J. Lamers, Saul Winegrad, Saskia Schlossarek, Lucie Carrier, Folkert J. ten Cate, Ger J.M. Stienen, Jolanda van der Velden
Journal: Circulation (2009)

Mutations in the MYBPC3 gene, encoding cardiac myosin-binding protein C (cMyBP-C), are a frequent cause of familial hypertrophic cardiomyopathy. In the present study, we investigated whether protein composition and function of the sarcomere are altered in a homogeneous familial hypertrophic cardiomyopathy patient group with frameshift mutations in MYBPC3 (MYBPC3(mut)).Comparisons were made between cardiac samples from MYBPC3 mutant carriers (c.2373dupG, n=7; c.2864_2865delCT, n=4) and nonfailing donors (n=13). Western blots with the use of antibodies directed against cMyBP-C did not reveal truncated cMyBP-C in MYBPC3(mut). Protein expression of cMyBP-C was significantly reduced in MYBPC3(mut) by 33+/-5%. Cardiac MyBP-C phosphorylation in MYBPC3(mut) samples was similar to the values in donor samples, whereas the phosphorylation status of cardiac troponin I was reduced by 84+/-5%, indicating divergent phosphorylation of the 2 main contractile target proteins of the beta-adrenergic pathway. Force measurements in mechanically isolated Triton-permeabilized cardiomyocytes demonstrated a decrease in maximal force per cross-sectional area of the myocytes in MYBPC3(mut) (20.2+/-2.7 kN/m(2)) compared with donor (34.5+/-1.1 kN/m(2)). Moreover, Ca(2+) sensitivity was higher in MYBPC3(mut) (pCa(50)=5.62+/-0.04) than in donor (pCa(50)=5.54+/-0.02), consistent with reduced cardiac troponin I phosphorylation. Treatment with exogenous protein kinase A, to mimic beta-adrenergic stimulation, did not correct reduced maximal force but abolished the initial difference in Ca(2+) sensitivity between MYBPC3(mut) (pCa(50)=5.46+/-0.03) and donor (pCa(50)=5.48+/-0.02).Frameshift MYBPC3 mutations cause haploinsufficiency, deranged phosphorylation of contractile proteins, and reduced maximal force-generating capacity of cardiomyocytes. The enhanced Ca(2+) sensitivity in MYBPC3(mut) is due to hypophosphorylation of troponin I secondary to mutation-induced dysfunction.
Bone stiffness in men with type 2 diabetes mellitus
Authors: Mai Asano, Michiaki Fukui, Hiroko Hosoda, Emi Shiraishi, Ichiko Harusato, Mayuko Kadono, Muhei Tanaka, Goji Hasegawa, Toshikazu Yoshikawa, Naoto Nakamura
Journal: Metabolism (2008)
Tumourigenic effect of vinorelbine on chemoresistant cancer stem cell renewal in colorectal cancer (CRC) and on metastasis
Authors: J. Giannios
Journal: Gut (2011)

<h3>Introduction</h3> Vinorelbine, which is an anticancer cytostatic agent, may shrink tumours but it stimulates production of more cancer stem cells, which then metastasise as a way to survive the cytostatic action of this drug. <h3>Methods</h3> Colorectal Ca obtained from patients were treated with vinorelbine. Post-treatment, the tumours were analysed for cancer stem cells using multi-colour flow cytometry methods for detecting markers and receptors on the surface of tumour cells. <h3>Results</h3> Post-treatment, we observed remission of the tumour cells and relapse of cancer stem cells characterised by a high proliferation index. There was overexpression of cancer stem cells (CSC) markers, Nanog and BMI1 which renew the CSCs. Other CSC markers that were overexpressed include CD44, CD133, CD44 and DR5 exhibiting cancer cell positive resilience, and chemoresistance. Vinorelbine activated the Notch signalling pathway, and phosphorylated the prosurvival mTOR pathway resulting in mitochondrial polarisation, and enhanced tumour cell proliferation. A common factor overexpressed in all cancer stem cells was Oct4, POU transcription factor protein that converts adult stem cells in cancer stem cells. This makes the square to sickle shift making super cancer cells, which form new incurable tumours despite extensive treatment with vinorelbine. Overexpression of these cancer stem cell markers is associated with resistance to vinorelbine leading to poor outcome for patients with colorectal Ca. This creates radioresistance, and chemoresistance for all conventional chemotherapeutic agents that might be administered after vinorelbine treatment. Thus, although vinorelbine reduces tumour size, it doesn9t result in long term cures due to induction of metastasis and recurrence. Between 25%&gt;40% of tumour cells consisted of cancer stem cells capable of propagating, reproducing and building metastatic and chemoresistant tumours after vinorelbine treatment. <h3>Conclusion</h3> To circumvent the distant metastasis of CRC induced by vinorelbine treatment due to stimulation of chemoresistant cancer stem cells, we will need new biological therapies which will eradicate with induction of apoptosis the CSCs through targeting of specific proteins on their plasma membrane.
A genomic analysis of the archaeal system Ignicoccus hospitalis-Nanoarchaeum equitans
Authors: Mircea Podar, Iain Anderson, Kira S Makarova, James G Elkins, Natalia Ivanova, Mark A Wall, Athanasios Lykidis, Kostantinos Mavromatis, Hui Sun, Matthew E Hudson, Wenqiong Chen, Cosmin Deciu, Don Hutchison, Jonathan R Eads, Abraham Anderson, Fillipe Fernandes, Ernest Szeto, Alla Lapidus, Nikos C Kyrpides, Milton H Saier, Paul M Richardson, Reinhard Rachel, Harald Huber, Jonathan A Eisen, Eugene V Koonin, Martin Keller, Karl O Stetter
Journal: Genome biology (2008)

The relationship between the hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans is the only known example of a specific association between two species of Archaea. Little is known about the mechanisms that enable this relationship.We sequenced the complete genome of I. hospitalis and found it to be the smallest among independent, free-living organisms. A comparative genomic reconstruction suggests that the I. hospitalis lineage has lost most of the genes associated with a heterotrophic metabolism that is characteristic of most of the Crenarchaeota. A streamlined genome is also suggested by a low frequency of paralogs and fragmentation of many operons. However, this process appears to be partially balanced by lateral gene transfer from archaeal and bacterial sources.A combination of genomic and cellular features suggests highly efficient adaptation to the low energy yield of sulfur-hydrogen respiration and efficient inorganic carbon and nitrogen assimilation. Evidence of lateral gene exchange between N. equitans and I. hospitalis indicates that the relationship has impacted both genomes. This association is the simplest symbiotic system known to date and a unique model for studying mechanisms of interspecific relationships at the genomic and metabolic levels.
Claims for the anabolic effects of growth hormone: a case of the Emperor’s new clothes?
Authors: M J Rennie
Journal: British Journal of Sports Medicine (2003)

This review examines the evidence that growth hormone has metabolic effects in adult human beings. The conclusion is that growth hormone does indeed have powerful effects on fat and carbohydrate metabolism, and in particular promotes the metabolic use of adipose tissue triacylglycerol. However, there is no proof that net protein retention is promoted in adults, except possibly of connective tissue. The overexaggeration of the effects of growth hormone in muscle building is effectively promoting its abuse and thereby encouraging athletes and elderly men to expose themselves to increased risk of disease for little benefit.
Propagating depolarization in anisotropic human and canine cardiac muscle: apparent directional differences in membrane capacitance. A simplified model for selective directional effects of modifying the sodium conductance on Vmax, tau foot, and the propagation safety factor.
Authors: M S Spach, P C Dolber, J F Heidlage, J M Kootsey, E A Johnson
Journal: Circulation Research (1987)

As yet there is no model or simulation that accounts for the anisotropic difference in the shape of the upstroke and safety factor of propagating cardiac action potentials: fast upstrokes occur with slow transverse propagation and slow upstrokes occur with fast longitudinal propagation. The purpose of this paper is to demonstrate, however, that a simplified cable model based on directional differences in the effective membrane capacitance predicts in detail the experimentally measured directionally dependent behavior of the upstroke in response to modification of the sodium conductance. Quinidine and lidocaine produced greater relative decreases in Vmax and conduction velocity with longitudinal propagation than with transverse propagation, as predicted on the basis that the shape differences should produce an anisotropic distribution in the membrane uptake of sodium channel binding drugs. The simulation predictions of the effects of positive shifts of the take-off potential due to premature action potentials were also confirmed experimentally: there was a greater relative decrease in conduction velocity, Vmax, and Vamp with a greater increase in tau foot during longitudinal propagation than with transverse propagation. The major anisotropic differences in shape occurred when the take-off potential approached the least negative value that produced a propagated response. The extensive experimental verification of the results of a simplified model based on directional differences of effective membrane capacitance, combined with directional differences in effective axial resistivity, provides an initial quantitative basis for the anisotropic behavior of propagating depolarization in response to modification of the sodium conductance in cardiac muscle.