tbuckley/cabot-search huggingface dataset:
Osteoarthritis research priorities: a report from a EULAR ad hoc expert committee
Authors: Philip G Conaghan, Margreet Kloppenburg, Georg Schett, Johannes W J Bijlsma
Journal: Annals of the Rheumatic Diseases (2014)

Health economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as health care, public health, education, social care, etc). This summary article presents the new CHEERS 2022 28-item checklist and recommendations for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer reviewed journals as well as the peer reviewers and editors assessing them for publication. However, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, as there is an increasing emphasis on transparency in decision making.
WHITE-SPOT DISEASE AND VITILIGO
Authors: J. L. BUNCH
Journal: British Journal of Dermatology (1918)

Journal Article WHITE‐SPOT DISEASE AND VITILIGO Get access J. L. BUNCH, M.D., D.Sc. J. L. BUNCH, M.D., D.Sc. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 30, Issue 4, 1 October 1918, Pages 203–207, https://doi.org/10.1111/j.1365-2133.1918.tb12380.x Published: 01 October 1918
A pilot trial of G3139, a bcl-2 antisense oligonucleotide,and paclitaxel in patients with chemorefractory small-cell lung cancer
Authors: C.M. Rudin, G.A. Otterson, A.M. Mauer, M.A. Villalona-Calero, R. Tomek, B. Prange, C.M. George, L. Szeto, E.E. Vokes
Journal: Annals of Oncology (2002)
Incidence of Bladder Cancer in Patients With Type 2 Diabetes Treated With Metformin or Sulfonylureas
Authors: Ronac Mamtani, Nick Pfanzelter, Kevin Haynes, Brian S. Finkelman, Xingmei Wang, Stephen M. Keefe, Naomi B. Haas, David J. Vaughn, James D. Lewis
Journal: Diabetes Care (2014)

Previous studies evaluating the effect of metformin on cancer risk have been impacted by time-related biases. To avoid these biases, we examined the incidence of bladder cancer in new users of metformin and sulfonylureas (SUs).This cohort study included 87,600 patients with type 2 diabetes in The Health Improvement Network database. Use of metformin or an SU was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared metformin use with SU use, adjusted for age, sex, smoking, obesity, and HbA1c level.We identified 196 incident bladder cancers in the metformin cohort and 66 cancers in the SU cohort. Use of metformin was not associated with decreased bladder cancer risk (HR 0.81 [95% CI 0.60-1.09]). This association did not differ by sex (P for interaction = 0.20). We observed no association with duration of metformin relative to SU use (3 to <4 years of use: 0.57 [0.25-1.34]; 4 to <5 years of use: 0.93 [0.30-2.85; ≥5 years of use: 1.18 [0.44-3.19]; P for trend = 0.26).Use of metformin is not associated with a decreased incidence of bladder cancer. Similar methods should be used to study other cancers that have previously been identified as potentially preventable with metformin.
Adaptive Loss of an Old Duplicated Gene During Incipient Speciation
Authors: Anthony J Greenberg, Jennifer R Moran, Shu Fang, Chung-I Wu
Journal: Molecular Biology and Evolution (2005)

To probe the role of natural selection in species origin, we performed a DNA polymorphism survey of the Drosophila melanogaster desaturase2 (ds2) locus. ds2 is responsible for a cuticular hydrocarbon difference between two behaviorally isolated races—Zimbabwe (Z) and Cosmopolitan (M). The ds2 allele prevalent in the Z populations is functional, while the allele from the M populations harbors a 16-bp deletion upstream of the gene which knocks out its expression. We find a signature of positive selection in the ds2 promoter, but not in the control gene, sas. This signature appears to be confined to the derived M population. We also find that the selection has been recent because the gene retains a signature of a selective sweep evidenced by the departure of Fay and Wu's H test from neutral expectation. We also find that ds2, as well as its duplicate pair ds1, has been maintained in the Drosophila genus for at least 40 Myr without any sign of adaptive change. Taken together with previous molecular genetic evidence, our results suggest that ds2 is one of the genes responsible for adaptive divergence of the Z and M races of D. melanogaster.
Medical provision and usage for the 1999 Everest marathon
Authors: D G W Buckler, F O'Higgins
Journal: British Journal of Sports Medicine (2000)

Take home message 

Sporting events in the most extreme of places and conditions can safely take place provided adequate medical facilities and resources are available, along with adequate education of the participants. 

The Everest marathon is a biannual race run from 5184 m near Everest base camp and finishing in the Sherpa capital of Namche Bazaar at 3446 m. It is recognised as the highest and possibly the toughest marathon race in the world. The runners start at a height at which the atmospheric pressure and inspired oxygen pressure are 50% of the value at sea level.1 It began in 1987 to an outcry from many altitude experts who felt the risks of running at that altitude were unjustifiable.2 However, it has proven to be a safe if tough race. There have been no fatalities. On average over the seven marathons, 5–10% of contestants have been unable to complete the whole race, some completing part of the course.3 In 1995 the course was unsafe because of a heavy snowfall, and only a half marathon was run. The previous races have been held in late November after the monsoon season. This year for the first time it was held in April, a warmer time of year. Daytime temperatures were typically around freezing, falling at night to −10°C.

The main medical problems facing previous medical teams have been altitude sickness, diarrhoea and vomiting, chest infections, and musculoskeletal disorders, especially anterior knee pains, contusions, and blistering of the feet.4 Knowledge of previous problems and the use of drug formularies from previous marathons helped to ensure that the expedition was adequately equipped.

This isolated route is away from medical access for long parts of the trek, requiring the medical team to be completely self sufficient. The race has potential for …
NPI-0052 Enhances Tumoricidal Response to Conventional Cancer Therapy in a Colon Cancer Model
Authors: James C. Cusack, Rong Liu, Lijun Xia, Ta-Hsiang Chao, Christine Pien, Wei Niu, Vito J. Palombella, Saskia T.C. Neuteboom, Michael A. Palladino
Journal: Clinical Cancer Research (2006)

Abstract Purpose: In the current study, we examine the effects of a novel proteasome inhibitor, NPI-0052 (salinosporamide A), on proteasome function and nuclear factor-κB activation and evaluate its ability to enhance treatment response in colon cancer xenografts when administered orally. Experimental Design: The effects of treatment on nuclear factor-κB activation, cell cycle regulation, and apoptosis were determined. The pharmacodynamic effect of NPI-0052 on 20S proteasome function was assayed in vivo following oral and i.v. drug administration and compared with treatment with bortezomib. The effect of combined treatment with chemotherapy was determined in a colon cancer xenograft model. Results: We found that NPI-0052 is a potent, well-tolerated proteasome inhibitor that has pharmacodynamic properties distinct from bortezomib in that it achieves significantly higher and more sustained levels of proteasome inhibition. When combined with chemotherapy, NPI-0052 increases apoptosis and shifts cells toward G2 cell cycle arrest. When added to chemotherapy in vivo [using combinations of 5-fluorouracil (5-FU), CPT-11, Avastin (bevacizumab), leucovorin, and oxaliplatin], NPI-0052 significantly improved the tumoricidal response and resulted in a 1.8-fold increased response to CPT-11, 5-FU, and leucovorin triple-drug combination (P = 0.0002, t test), a 1.5-fold increased response to the oxaliplatin, 5-FU, and leucovorin triple-drug combination (P = 0.013, t test), and a 2.3-fold greater response to the CPT-11, 5-FU, leucovorin, and Avastin regimen (P = 0.00057). Conclusions: The high level of proteasome inhibition achieved by NPI-0052 is well tolerated and significantly improves the tumoricidal response to multidrug treatment in a colon cancer xenograft model. Further evaluation of this novel proteasome inhibitor in clinical trials is indicated.
Evaluation of the prognostic and predictive value of p53 and Bcl-2 in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy
Authors: V. Malamou-Mitsi, H. Gogas, U. Dafni, A. Bourli, T. Fillipidis, M. Sotiropoulou, D. Vlachodimitropoulos, S. Papadopoulos, O. Tzaida, G. Kafiri, V. Kyriakou, S. Markaki, I. Papaspyrou, E. Karagianni, K. Pavlakis, T. Toliou, C.D. Scopa, P. Papakostas, D. Bafaloukos, C. Christodoulou, G. Fountzilas
Journal: Annals of Oncology (2006)
Suppression of Iron-Regulatory Hepcidin by Vitamin D
Authors: Justine Bacchetta, Joshua J. Zaritsky, Jessica L. Sea, Rene F. Chun, Thomas S. Lisse, Kathryn Zavala, Anjali Nayak, Katherine Wesseling-Perry, Mark Westerman, Bruce W. Hollis, Isidro B. Salusky, Martin Hewison
Journal: Journal of the American Society of Nephrology (2013)

The antibacterial protein hepcidin regulates the absorption, tissue distribution, and extracellular concentration of iron by suppressing ferroportin-mediated export of cellular iron. In CKD, elevated hepcidin and vitamin D deficiency are associated with anemia. Therefore, we explored a possible role for vitamin D in iron homeostasis. Treatment of cultured hepatocytes or monocytes with prohormone 25-hydroxyvitamin D or active 1,25-dihydroxyvitamin D decreased expression of hepcidin mRNA by 0.5-fold, contrasting the stimulatory effect of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D on related antibacterial proteins such as cathelicidin. Promoter-reporter and chromatin immunoprecipitation analyses indicated that direct transcriptional suppression of hepcidin gene (HAMP) expression mediated by 1,25-dihydroxyvitamin D binding to the vitamin D receptor caused the decrease in hepcidin mRNA levels. Suppression of HAMP expression was associated with a concomitant increase in expression of the cellular target for hepcidin, ferroportin protein, and decreased expression of the intracellular iron marker ferritin. In a pilot study with healthy volunteers, supplementation with a single oral dose of vitamin D (100,000 IU vitamin D2) increased serum levels of 25D-hydroxyvitamin D from 27±2 ng/ml before supplementation to 44±3 ng/ml after supplementation (P<0.001). This response was associated with a 34% decrease in circulating levels of hepcidin within 24 hours of vitamin D supplementation (P<0.05). These data show that vitamin D is a potent regulator of the hepcidin-ferroportin axis in humans and highlight a potential new strategy for the management of anemia in patients with low vitamin D and/or CKD.
Elevated Levels of Activin A in Heart Failure
Authors: Arne Yndestad, Thor Ueland, Erik Øie, Geir Florholmen, Bente Halvorsen, Håvard Attramadal, Svein Simonsen, Stig S. Frøland, Lars Gullestad, Geir Christensen, Jan Kristian Damås, Pål Aukrust
Journal: Circulation (2004)

Although modulation of inflammatory processes has been suggested as a new treatment modality in heart failure (HF), our knowledge about abnormalities in the cytokine network during HF is still limited. On the basis of a previous cDNA array study examining peripheral blood mononuclear cells from HF patients, we hypothesized a role for activin A, a member of the transforming growth factor (TGF)-beta superfamily, in the pathogenesis of HF.This study had 4 main and novel findings. First, serum levels of activin A were significantly elevated in patients with HF (n=86) compared with healthy control subjects (n=20), with increasing levels according to disease severity as assessed by clinical, hemodynamic, and neurohormonal parameters. Second, compared with control subjects, HF patients, as determined by real-time quantitative reverse transcriptase polymer chain reaction, also had markedly increased gene expression of the activin A subunit activin betaA in T cells but not in monocytes. Third, in a rat model of HF, we demonstrated a concerted induction of the gene expression of activin betaA and activin receptors IA, IB, IIA, and IIB after myocardial infarction. Immunohistochemical analysis localized activin A solely to cardiomyocytes. Finally, activin A markedly increased gene expression of mediators involved in infarction healing and myocardial remodeling (ie, atrial natriuretic peptide, brain natriuretic peptide, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, transforming growth factor-beta1, and monocyte chemoattractant protein-1) in neonatal rat cardiomyocytes.Together with our demonstration of activin A-induced gene expression in neonatal cardiomyocytes of mediators related to myocardial remodeling, the expression pattern of activin A during clinical and experimental HF suggests an involvement of this cytokine in the pathogenesis of HF.
Overall Survival: Patient Outcome, Therapeutic Objective, Clinical Trial End Point, or Public Health Measure?
Authors: Everardo D. Saad, Marc Buyse
Journal: Journal of Clinical Oncology (2012)

In recent years, improvements in systemic therapy for the most common types of advanced solid tumors have considerably expanded the therapeutic arsenal in medical oncology. The introduction of novel chemotherapy and hormonal agents in the 1990s and of various molecularly targeted therapies during the last decade has improved the outlook of patients with the most common malignancies, including metastatic breast cancer, 1-5 colorectal cancer, 6-8 prostate cancer, 9-11 head and neck cancer, 12,13 gastric cancer, 14,15 renal cell carcinoma, 16-18 non– small-cell lung cancer, 19-21 and pancreatic cancer. 22 The increasing availability of active agents makes clinical development of novel therapies progressively more complex. Also, because of the growing number of drugs, combinations, and sequences that require testing in clinical trials, and given the opportunity to test novel therapies in different lines of treatment, the choice of clinical trial end points has become more critical than ever before. Although improvements in overall survival (OS) remain the ultimate treatment goal in oncology, OS gain seems increasingly more elusive in clinical trials in settings in which effective post-trial therapy exists. This apparent contradiction is reflected in the literature by arguments in which the function of OS as an end point is not distinguished from its role as a treatment goal. Thus, in statements such as “prolongation of OS is generally the most relevant measure of clinical benefit in a randomized clinical trial of an experimental treatment,” 23(p2439) the different roles played by survival in clinical practice and in the trial setting are not distinguished. In this commentary, we propose that a clear distinction ought to be made among survival as a goal desired by patients, clinicians, clinical trialists, and public health policymakers.
Immunoglobulin-binding Sites of Human FcαRI (CD89) and Bovine Fcγ2R Are Located in their Membrane-distal Extracellular Domains
Authors: H. Craig Morton, Ger van Zandbergen, Cees van Kooten, Chris J. Howard, Jan G. J. van de Winkel, Per Brandtzaeg
Journal: The Journal of Experimental Medicine (1999)

To localize the immunoglobulin (Ig)-binding regions of the human Fcalpha receptor (FcalphaRI, CD89) and the bovine Fcgamma2 receptor (bFcgamma2R), chimeric receptors were generated by exchanging comparable regions between these two proteins. FcalphaRI and bFcgamma2R are highly homologous and are more closely related to each other than to other human and bovine FcRs. Nevertheless, they are functionally distinct in that FcalphaRI binds human IgA (hIgA) but not bovine IgG2 (bIgG2), whereas bFcgamma2R binds bIgG2 but not hIgA. FcalphaRI and bFcgamma2R possess extracellular regions consisting of two Ig-like domains, a membrane-distal extracellular domain (EC1), a membrane-proximal EC domain (EC2), a transmembrane region, and a short cytoplasmic tail. Chimeras constructed by exchanging complete domains between these two receptors were transfected to COS-1 cells and assayed for their ability to bind hIgA- or bIgG2-coated beads. The results showed that the Ig-binding site of both FcalphaRI and bFcgamma2R is located within EC1. Supporting this observation, monoclonal antibodies that blocked IgA binding to FcalphaRI were found to recognize epitopes located in this domain. In terms of FcR-Ig interactions characterized thus far, this location is unique and surprising because it has been shown previously that leukocyte FcgammaRs and FcepsilonRI bind Ig via sites principally located in their EC2 domains.
A METHOD FOR ESTIMATING INSTANTANEOUS PULMONARY CAPILLARY BLOOD FLOW IN MAN*
Authors: Karlman Wasserman, Julius H. Comroe
Journal: Journal of Clinical Investigation (1962)

The use of soluble, "inert" gases to measure cardiac output dates from 1910 when Bornstein (1) used nitrogen as the test gas.He stated the principle that, if a gas does not react chemically with blood, its rate of absorption is proportional to the quantity of blood flowing through the pul- monary capillary bed.If the solubility coefficient of the gas in blood and the difference between the partial pressures of the gas in alveolar air and in pulmonary arterial blood are known, and if equilibrium of gas tensions across the alveolar- capillary membranes is assumed, the pulmonary capillary blood flow may be calculated.Krogh and Lindhard (2) improved on Bornstein's method by using nitrous oxide, a much more soluble gas.There followed a series of modifications of gas methods for measuring cardiac output (3-5), but the introduction of the direct Fick technique and the increasing use of methods based on the Stewart-Hamilton indicator dilution principle led to their disuse.Lee and DuBois (6) used a body plethysmograph (7) to measure the instantaneous rate of absorption of nitrous oxide from the lungs in man.This ingenious method has many advantages over the direct Fick and indicator dilution methods because it permits the calculation of instantaneous pulmonary capillary blood flow at frequent inter- vals without the introduction of needles or cathe- ters into the cardiovascular system.Their method requires of the subject only that he sit in an air- tight chamber about the size of a phone booth, take one deep breath of nitrous oxide and then
Modification of the Association Between Obesity and Lethal Prostate Cancer by TMPRSS2:ERG
Authors: Andreas Pettersson, Rosina T. Lis, Allison Meisner, Richard Flavin, Edward C. Stack, Michelangelo Fiorentino, Stephen Finn, Rebecca E. Graff, Kathryn L. Penney, Jennifer R. Rider, Elizabeth J. Nuttall, Neil E. Martin, Howard D. Sesso, Michael Pollak, Meir J. Stampfer, Philip W. Kantoff, Edward L. Giovannucci, Massimo Loda, Lorelei A. Mucci
Journal: JNCI Journal of the National Cancer Institute (2013)

TMPRSS2:ERG is a hormonally regulated gene fusion present in about half of prostate tumors. We investigated whether obesity, which deregulates several hormonal pathways, interacts with TMPRSS2:ERG to impact prostate cancer outcomes. The study included 1243 participants in the prospective Physicians' Health Study and Health Professionals Follow-Up Study diagnosed with prostate cancer between 1982 and 2005. ERG overexpression (a TMPRSS2:ERG marker) was assessed by immunohistochemistry of tumor tissue from radical prostatectomy or transurethral resection of the prostate. Body mass index (BMI) and waist circumference, measured on average 1.3 years and 5.3 years before diagnosis, respectively, were available from questionnaires. Data on BMI at baseline was also available. We used Cox regression to calculate hazard ratios and 95% confidence intervals (CIs). All statistical tests were two-sided. During a mean follow-up of 12.8 years, 119 men developed lethal disease (distant metastases or prostate cancer death). Among men with ERG-positive tumors, the multivariable hazard ratio for lethal prostate cancer was 1.48 (95% CI = 0.98 to 2.23) per 5-unit increase in BMI before diagnosis, 2.51 (95% CI = 1.26 to 4.99) per 8-inch increase in waist circumference before diagnosis, and 2.22 (95% CI = 1.35 to 3.63) per 5-unit increase in BMI at baseline. The corresponding hazard ratios among men with ERG-negative tumors were 1.10 (95% CI = 0.76 to1.59; Pinteraction = .24), 1.14 (95% CI = 0.62 to 2.10; Pinteraction = .09), and 0.78 (95% CI = 0.52 to 1.19; Pinteraction = .001). These results suggest that obesity is linked with poorer prostate cancer prognosis primarily in men with tumors harboring the gene fusion TMPRSS2:ERG .
Prediction of axillary lymph node status in male breast carcinoma
Authors: C. Vaysse, J. Sroussi, P. Mallon, J.G. Feron, A.L. Rivain, C. Ngo, C. Belichard, S. Lasry, J.Y. Pierga, B. Couturaud, A. Fitoussi, F. Laki, V. Fourchotte, S. Alran, Y. Kirova, A. Vincent-Salomon, X. Sastre-Garau, B. Sigal-Zafrani, R. Rouzier, F. Reyal
Journal: Annals of Oncology (2012)
A Phase I and Pharmacokinetic Study of Lapatinib in Combination with Letrozole in Patients with Advanced Cancer
Authors: Quincy S.C. Chu, Mary E. Cianfrocca, Lori J. Goldstein, Meg Gale, Nicholas Murray, Jill Loftiss, Nikita Arya, Kevin M. Koch, Lini Pandite, Ronald A. Fleming, Elaine Paul, Eric K. Rowinsky
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The main objectives of this phase I and pharmacokinetic, open-label study were to determine the optimally tolerated regimen (OTR), safety, pharmacokinetics, and clinical activity of lapatinib in combination with letrozole in patients with advanced solid malignancies. Experimental Design: Patients with advanced breast cancer with immunohistochemically detectable estrogen or progesterone receptors or other cancers were eligible. Doses of lapatinib were escalated in cohorts of three subjects from 1,250 to a maximum of 1,500 mg/d based on dose-limiting toxicities in the first treatment cycle. The letrozole dose was fixed at 2.5 mg/d. Additional patients were enrolled at the OTR dose level to further evaluate safety and for pharmacokinetic analyses. Results: Thirty-nine patients were enrolled in the study: 12 in the dose-escalation group, 7 in the OTR safety group, and 20 in the pharmacokinetic group. The OTR dose level was identified as 1,500 mg/d lapatinib and 2.5 mg/d letrozole. The most common (&amp;gt;25% of patients) drug-related adverse events were diarrhea (77%), rash (62%), nausea (46%), and fatigue (26%). No significant differences were observed in the pharmacokinetic variables (Cmax and AUC) of lapatinib and letrozole when coadministered compared with single-agent administration. One patient with endometrial cancer had a confirmed partial response. Conclusions: Clinically relevant doses of lapatinib in combination with letrozole were well tolerated and did not result in a pharmacokinetic interaction, and clinical antitumor activity was observed.