tbuckley/cabot-search huggingface dataset:
A Vasculature-Targeting Regimen of Preoperative Docetaxel with or without Bevacizumab for Locally Advanced Breast Cancer: Impact on Angiogenic Biomarkers
Authors: Joseph Baar, Paula Silverman, Janice Lyons, Pingfu Fu, Fadi Abdul-Karim, Nicholas Ziats, Jay Wasman, Paul Hartman, John Jesberger, Leda Dumadag, Erin Hohler, Rosemary Leeming, Robert Shenk, Helen Chen, Keith McCrae, Afshin Dowlati, Scot C. Remick, Beth Overmoyer
Journal: Clinical Cancer Research (2009)

Taxanes have effects on angiogenesis causing difficulties in separating biological effects of chemotherapy from those due to angiogenesis inhibitors. This randomized phase II trial was designed to evaluate the additional biomarker effect on angiogenesis when bevacizumab is added to docetaxel.Patients with inoperable breast cancer were randomized to either 2 cycles of preoperative docetaxel (D) 35 mg/m(2) i.v. weekly for 6 weeks, followed by a 2-week break; or docetaxel with bevacizumab 10 mg/kg i.v. every other week for a total of 16 weeks (DB). Plasma and serum markers of endothelial damage, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and tumor microvessel density were assessed before treatment and at the end of each preoperative cycle.Forty-nine patients were randomized (DB, 24; D, 25). There was no difference in overall clinical response, progression-free survival, or overall survival. Vascular endothelial growth factor increased during treatment; more so with DB (P < 0.0001). Vascular cell adhesion molecule-1 (VCAM-1) also increased (P < 0.0001); more so with DB (P = 0.069). Intercellular adhesion molecule increased (P = 0.018) and E-selectin decreased (P = 0.006) overall. Baseline levels of VCAM-1 and E-selectin correlated with clinical response by univariate analysis. DCE-MRI showed a greater decrease in tumor perfusion calculated by initial area under the curve for the first 90 seconds in DB (P = 0.024). DCE-MRI also showed an overall decrease in tumor volume (P = 0.012).Bevacizumab plus docetaxel caused a greater increase in vascular endothelial growth factor and VCAM-1, and a greater reduction in tumor perfusion by DCE-MRI compared with docetaxel. Clinical outcomes of inoperable breast cancer were predicted by changes in VCAM-1 and E-selectin.
The effect of ankle and knee bracing on joint stability and performance during different tasks
Authors: Jim Richards
Journal: British Journal of Sports Medicine (2011)

Braces are commonly used for prevention and treatment of ankle and knee injuries by individuals who take part in sporting activities which involve challenges to the stability of joints. However, the use of ankle and knee bracing is less common in the conservative management of joint pain and pathology which is not sporting related. In all cases, the braces are attempting to provide improved stability of the joints in the coronal and transverse plane, but there has been much debate on whether bracing offers a functional or proprioceptive effect. Much of the biomechanical testing to date has been conducted using very simple biomechanical models, which allow do not allow accurate measures of the movement and moments about the foot, ankle and knee joints in the coronal and transverse planes. From this it is safe to say that the effect of ankle and knee bracing on the coronal and transverse plane mechanics of the lower limb have not received any adequate attention in the research literature, although clinically these are the very things that such devices often claim to support and control. The importance of coronal and torsional movement and moments of the foot, ankle and knee joints has previously been identified. However, little or no work has been published to see how the torsional and coronal mechanics of the ankle and knee joints are changed during functional tasks using devices designed to control and give stability to these joints. This workshop will consider the action of several methods of orthotic management of the ankle and knee joints on a variety of conditions by considering the research evidence. In each case, advanced methods of analysis have been used to determine the biomechanical changes and how these can be related to the clinical benefits. This will highlight not just the effects about the foot and ankle but also the effects of treating the foot and ankle on the knee, hip and pelvis. The data on a variety of methods of bracing for patellofemoral pain and ankle stability will be considered, with particular attention on the nature of the functional and proprioceptive effects of each method.
Non-viral delivery of nuclear factor- B decoy ameliorates murine inflammatory bowel disease and restores tissue homeostasis
Authors: C. G De Vry, S. Prasad, L. Komuves, C. Lorenzana, C. Parham, T. Le, S. Adda, J. Hoffman, N. Kahoud, R. Garlapati, R. Shyamsundar, K. Mai, J. Zhang, T. Muchamuel, M. Dajee, B. Schryver, L. M McEvoy, R. O Ehrhardt
Journal: Gut (2006)

<b>Background:</b> Nuclear factor-κB (NF-κB) is a key transcriptional regulator of inflammatory bowel disease (IBD). <b>Aim:</b> To investigate the therapeutic potential of a locally administered "non-viral" nuclear factor-κB decoy (NFκBD) in multiple experimental models of IBD. <b>Methods:</b> A fully phosphorothioated decoy oligonucleotide with improved stability that specifically binds NF-κB and blocks inflammatory mediators regulated by this transcription factor without the help of viral envelope-assisted delivery was developed. The therapeutic effects of NFκBD were studied in the trinitrobenzene sulphonic acid, oxazolone and dextran sodium sulphate induced colitis models. <b>Results:</b> Intracolonic administration of NFκBD results in the delivery of NFκBD to inflammatory cells and a reduction of NF-κB heterodimers. In the T helper cell 1-driven trinitrobenzene sulphonic acid-induced colitis model, mice receiving NFκBD treatment exhibit a dose-dependent reduction in disease severity and a more rapid recovery to normal body weight, similar to a clinically relevant dose of budesonide. Clinical efficacy was corroborated by considerable reductions in colitis pathology and tissue levels of several pro-inflammatory markers, including tumour necrosis factor α, interleukin 6, interleukin 1β and monocyte chemotactic protein 1. NFκBD also mitigates disease activity in the T helper cell 2-like oxazolone colitis and epithelial injury-related acute dextran sodium sulphate colitis models. Interestingly, restoration of tissue homeostasis is observed in NFκBD-treated animals with the rapid re-emergence of functional goblet cells and a return to normal patterns of cell proliferation in the mucosal epithelium and smooth muscle cell layers. <b>Conclusions:</b> These data support the potential use of "naked" NFκBD as a cross-functional therapeutic in IBD, and show for the first time that it can facilitate the restoration of colon homeostasis and function.
Beyond Tissue Injury—Damage-Associated Molecular Patterns, Toll-Like Receptors, and Inflammasomes Also Drive Regeneration and Fibrosis
Authors: Hans-Joachim Anders, Liliana Schaefer
Journal: Journal of the American Society of Nephrology (2014)

Tissue injury initiates an inflammatory response through the actions of immunostimulatory molecules referred to as damage-associated molecular patterns (DAMPs). DAMPs encompass a group of heterogenous molecules, including intracellular molecules released during cell necrosis and molecules involved in extracellular matrix remodeling such as hyaluronan, biglycan, and fibronectin. Kidney-specific DAMPs include crystals and uromodulin released by renal tubular damage. DAMPs trigger innate immunity by activating Toll-like receptors, purinergic receptors, or the NLRP3 inflammasome. However, recent evidence revealed that DAMPs also trigger re-epithelialization upon kidney injury and contribute to epithelial-mesenchymal transition and, potentially, to myofibroblast differentiation and proliferation. Thus, these discoveries suggest that DAMPs drive not only immune injury but also kidney regeneration and renal scarring. Here, we review the data from these studies and discuss the increasingly complex connection between DAMPs and kidney diseases.
No Evidence for Genetically Determined Alteration in Insulin Secretion or Sensitivity Predisposing to Type 1 Diabetes
Authors: Mohammed I. Hawa, Riccardo Bonfanti, Christina Valeri, Michela Delli Castelli, Huriya Beyan, R. David G. Leslie
Journal: Diabetes Care (2005)

OBJECTIVE— To determine whether inherited changes in insulin secretion or sensitivity could predispose to type 1 diabetes, we studied identical twins of type 1 diabetic patients. RESEARCH DESIGN AND METHODS— We studied prospectively a consecutive series of 27 identical twins of patients with type 1 diabetes who were initially nondiabetic, as well as 14 control subjects, over a period of 18 years. Of these 27 twins, 15 remain nondiabetic (now estimated at low disease risk) and 12 developed diabetes (pre-diabetic twins). Subjects were tested when not diabetic on at least two occasions with an intravenous glucose tolerance test (IVGTT), and we estimated insulin secretion as first-phase insulin response (FPIR), glucose clearance (Kg), and insulin sensitivity both by homeostasis model assessment of insulin resistance (HOMA-IR) and relative to insulin response by the basal HOMA-IR–to–FPIR ratio. RESULTS— Twins now at low risk and control subjects had similar fasting blood glucose and insulin levels, FPIR, Kg, HOMA-IR, and HOMA-IR–to–FPIR ratio. In contrast, pre-diabetic twins compared with control twins had higher fasting insulin levels (10.3 ± 6.0 vs. 4.6 ± 4.0 mIU/ml), lower FPIR (245 ± 129 vs. 796 ± 622 mIU · ml−1 · 10 min−1), lower Kg (1.5 ± 0.6 vs. 2.6 ± 0.8% per min), and higher HOMA-IR–to–FPIR ratio (0.007 ± 0.005 vs. 0.001 ± 0.0009) (all P &amp;lt; 0.01). CONCLUSIONS— These observations in low-risk nondiabetic identical twins failed to identify a familial alteration in either insulin secretion or sensitivity predisposing to type 1 diabetes.
A genetic code alteration generates a proteome of high diversity in the human pathogen Candida albicans
Authors: Ana C Gomes, Isabel Miranda, Raquel M Silva, Gabriela R Moura, Benjamin Thomas, Alexandre Akoulitchev, Manuel AS Santos
Journal: Genome biology (2007)

Genetic code alterations have been reported in mitochondrial, prokaryotic, and eukaryotic cytoplasmic translation systems, but their evolution and how organisms cope and survive such dramatic genetic events are not understood.Here we used an unusual decoding of leucine CUG codons as serine in the main human fungal pathogen Candida albicans to elucidate the global impact of genetic code alterations on the proteome. We show that C. albicans decodes CUG codons ambiguously and tolerates partial reversion of their identity from serine back to leucine on a genome-wide scale.Such codon ambiguity expands the proteome of this human pathogen exponentially and is used to generate important phenotypic diversity. This study highlights novel features of C. albicans biology and unanticipated roles for codon ambiguity in the evolution of the genetic code.
Preparation and characterization of decellularized cornea using high-hydrostatic pressurization for corneal tissue engineering
Authors: Yoshihide Hashimoto, Seiichi Funamoto, Shuji Sasaki, Takako Honda, Shinya Hattori, Kwangwoo Nam, Tsuyoshi Kimura, Manabu Mochizuki, Toshiya Fujisato, Hisatoshi Kobayashi, Akio Kishida
Journal: Biomaterials (2010)
Public Health Medical Officers
Authors: F. J. G. Lishman
Journal: BMJ (1967)

and enter "digs" on a lodging allowance prior to commencing a course costing the taxpayer possibly anything up to £800-a sum which would cover the cost of hundreds of medical examinations.In cases such as this, the job which was given up is possibly no longer available on terminating the course prematurely.Only those applicants who are considered, by a panel, technically suitable for travelling require medical examination.
Three-Year Outcome following Holmium Laser Enucleation of the Prostate Combined with Mechanical Morcellation in 330 Consecutive Patients
Authors: Ivano Vavassori, Sergio Valenti, Richard Naspro, Alberto Vismara, Vincenzo dell'Acqua, Alberto Manzetti, Rodolfo Hurle
Journal: European Urology (2007)
Shifting to outpatient management of acute myeloid leukemia: a prospective experience
Authors: M.L. Savoie, T.J. Nevil, K.W. Song, D.L. Forrest, D.E. Hogge, S.H. Nantel, J.D. Shepherd, C.A. Smith, H.J. Sutherland, C.L. Toze, J.C. Lavoie
Journal: Annals of Oncology (2006)
Molecular epidemiology of erythropoietic protoporphyria in the U.K.
Authors: S.D. Whatley, N.G. Mason, S.A. Holme, A.V. Anstey, G.H. Elder, M.N. Badminton
Journal: British Journal of Dermatology (2010)

Background Erythropoietic protoporphyria (EPP) is a cutaneous porphyria caused by mutations in the ferrochelatase (FECH) or, less frequently, the delta‐aminolaevulinate synthase 2 (ALAS2) gene. Predictive genetic counselling requires accurate molecular diagnosis and knowledge of patterns of inheritance. Objectives To investigate the molecular epidemiology of EPP in the U.K. Methods DNA samples from 191 unrelated patients resident in the U.K. were analysed for mutations in the FECH and ALAS2 genes and for the FECH IVS3‐48 dimorphism. Results Mutations were identified in 179 (94%) patients. Most (169; 94%) had a FECH mutation on one allele and were classified as having pseudodominant EPP (psdEPP); seven (4%) patients had FECH mutations on both alleles (autosomal recessive EPP) and three (2%) patients had ALAS2 mutations (X‐linked dominant protoporphyria). The FECH IVS3‐48C allele was strongly associated with psdEPP and with the absence of mutations at the FECH or ALAS2 loci. Fifty‐six FECH mutations were identified, 19 being previously unreported. Missense mutations were predominant in autosomal recessive EPP (82%) but not in psdEPP (32%). One mutation (c.314 + 2T>G) was present in 41 (24%) of EPP families, most of whom appeared to be descended from a common ancestor resident in the north of England. Conclusions These data define the prevalence and molecular epidemiology of each type of EPP in the U.K.
Prevalence of long-lasting IGRA positivity in Portuguese healthcare workers
Authors: José Torres Costa, Chandrasekharan Kesavachandran, Albert Nienhaus
Journal: European Respiratory Journal (2012)

Introduction: Tuberculosis screening in healthcare workers (HCW) is facilitated by the introduction of IGRA. However, uncertainties regarding the interpretation of IGRAs in the serial testing of HCWs remain.  Method: At the University of Oporto Medical Centre in Portugal, IGRAs were introduced in HCW screening in 2007. Screening is repeated after unprotected contact with TB patients or annually depending on the risk assessment. The QuantiFERON-TB Gold In-Tube (QFT) is used and the results of the screening are assessed in a standardised database.  Results: Between 2007 and 2011, a total of 539 HCWs were tested with IGRA at least three times. 235 HCWs were tested four times. In all three tests, 15.6% were positive, in all four consecutive IGRAs, 10.2% were positive. 49.9% were negative in all three tests and 44.3% were negative in all four consecutive IGRAs. If the concentration of the first IGRA was below 0.2 IU/mL, 72.8% remained negative in the following two IGRAs compared to 26.3% if the first IGRA showed a concentration of between 0.2 and   Conclusion: The prevalence of persistently positive IGRA is lower than expected. The persistency of positive or negative IGRA results does depend on the concentration observed in the first IGRA. This further underlines the need for a grey zone (e.g. 0.2 –
Stimulation of L-type Ca2+ current in human atrial myocytes by insulin
Authors: S Maier
Journal: Cardiovascular Research (1999)

Objective: The L-type calcium current (ICa,L) in isolated human atrial myocytes was investigated as a possible target of insulin in the regulation of cardiac function. Methods: Atrial myocytes were obtained from patients undergoing cardiac surgery. Using the whole-cell configuration of the patch-clamp technique, we investigated the stimulation of ICa,L by insulin in single human atrial myocytes. Results: We found a dose-dependent stimulation of ICa,L by insulin at concentrations of 100 nM, 1 μM and 10 μM. Maximum stimulation of ICa,L over basal ICa,L was 140±12% (n=11) at 10 μM insulin. The maximum conductance of ICa,L was increased by 10 μM insulin from 4.0±0.3 nS to 8.3±1.0 nS (n=6). The stimulation of ICa,L by insulin was dose-dependent and reversible. Isoproterenol (10 nM) that stimulates ICa,L by 271±48% (n=10) over basal ICa,L acted faster than insulin. The half-maximum stimulation of ICa,L by isoproterenol and insulin (10 μM) was reached after 31±2 s and 52±5 s, respectively. The insulin effect shown was totally reversed by acetylcholine (3 μM) which is known to inhibit adenylyl cyclase activity/cAMP-production via Gi-proteins. Also, the selective insulin receptor tyrosine kinase inhibitor (hydroxy-2-naphthanelyl-methyl)phosphonic acid completely inhibited the insulin induced effect. Conclusion: Our data show that insulin stimulates the L-type calcium current in isolated human atrial myocytes in a dose-dependent and reversible manner which appears to involve the insulin receptor tyrosine kinase. Insulin regulation of ICa,L in human atrial myocytes may be an interesting system for the analysis of the metabolic syndrome in man.
Serum uric acid-its relationship to lean body mass sex, plasma urea, intracellular potassium and packed cell volume in a normal population group.
Authors: A C Kennedy, J Brennan, J Anderson, P Brooks, W W Buchanan, W C Dick
Journal: Annals of the Rheumatic Diseases (1975)

It is concluded that osteoporosis is a generalized phenomenon in rheumatoid arthritis, relating more to the duration of the arthritis than to the presence of treatment with corticosteroid therapy.
Immunoregulatory subsets of the T helper and T suppressor cell populations in homosexual men with chronic unexplained lymphadenopathy.
Authors: J K Nicholson, J S McDougal, T J Spira, G D Cross, B M Jones, E L Reinherz
Journal: Journal of Clinical Investigation (1984)

Unexplained, generalized lymphadenopathy in homosexual men, which can be a prodrome to the acquired immunodeficiency syndrome, is associated with impaired cell-mediated immunity, a low ratio of T helper-inducer to T suppressor-cytotoxic cells (defined by the T4 and T8 monoclonal antibodies), and hypergammaglobulinemia. We performed double-marker studies on T cells by using a panel of monoclonal antibodies (Ia, T17, TQ1, and Leu-8), which reportedly detect activation or functional subsets of the T4 and T8 T cell populations. The T4:TQ1- or T4:Leu-8- subset, which is the major helper subset for B cell responses, is normally represented in lymphadenopathy patients. A depression in the reciprocal subset, T4:TQ1+ or T4:Leu-8+, accounts for the T4 T cell defect. Similarly, the TQ1 and Leu-8 markers delineate the abnormality of T8 T cells: the T8:TQ1- or T8:Leu-8- subset is elevated, whereas the T8:TQ1+ or T8:Leu-8+ subset is normally represented. We found no evidence of excessive activation of T4 T cells by using the T17 or Ia monoclonal antibodies. We did find an overall increase in Ia-positive T cells; however, this was due to increased T8:Ia+ cells. In functional studies, immunoglobulin production induced by pokeweed was subnormal. Most lymphadenopathy patients had normal T helper cell function when combined with normal B cells. The dampened pokeweed responses could be partially explained by depression of the T4:TQ1+ (or T4:Leu-8+) subset (which has minor help-associated function) and/or greater than expected suppression. However, subnormal pokeweed responses could not be totally explained by immunoregulatory T cell abnormalities because we also found an intrinsic defect in the B cell responses of lymphadenopathy patients.
Part I: Training Principles and Adaptive Responses
Authors: J. D. Brooke, J. E. Knowles
Journal: British Journal of Sports Medicine (1974)

yd. run 600 yd.run 12 min.run 600 yd.run 600 yd.run 600 yd.run 600 yd.run ri 1 0.97 0.94 0.80 0.92 0.80 Correlation with V02 max.-0.66 -0.64 0.897 -0.85 -0.79 -0.67 -0.65 0.90 -0.62 *In a private communication to Cooper (op.cit
Age preferences in mates reflect sex differences in human reproductive strategies
Authors: Douglas T. Kenrick, Richard C. Keefe
Journal: Behavioral and Brain Sciences (1992)

Abstract The finding that women are attracted to men older than themselves whereas men are attracted to relatively younger women has been explained by social psychologists in terms of economic exchange rooted in traditional sex-role norms. An alternative evolutionary model suggests that males and females follow different reproductive strategies, and predicts a more complex relationship between gender and age preferences. In particular, males' preferences for relatively younger females should be minimal during early mating years, but should become more pronounced as the male gets older. Young females are expected to prefer somewhat older males during their early years and to change less as they age. We briefly review relevant theory and present results of six studies testing this prediction. Study 1 finds support for this gender-differentiated prediction in age preferences expressed in personal advertisements. Study 2 supports the prediction with marriage statistics from two U.S. cities. Study 3 examines the cross-generational robustness of the phenomenon, and finds the same pattern in marriage statistics from 1923. Study 4 replicates Study 1 using matrimonial advertisements from two European countries, and from India. Study 5 finds a consistent pattern in marriages recorded from 1913 through 1939 on a small island in the Philippines. Study 6 reveals the same pattern in singles advertisements placed by financially successful American women and men. We consider the limitations of previous normative and evolutionary explanations of age preferences and discuss the advantages of expanding previous models to include the life history perspective.