tbuckley/cabot-search huggingface dataset:
A Tangled Web: Factors Likely to Affect the Efficacy of Screening Mammography
Authors: C J Baines, R Dayan
Journal: JNCI Journal of the National Cancer Institute (1999)

Given the direct and indirect costs of mammographic breast cancer screening in North America (1,2), any evidence leading to the improved efficacy of screening mammography should be welcome. The importance of high technical standards to achieve mammographic accuracy has been recognized (3). Improved accuracy should lead to improved efficacy, namely, further reductions in mortality from breast cancer. The efficacy of breast screening is most contested in women who are 40–49 years old (4), many of whom are premenopausal. In this group, a 16% reduction in breast cancer mortality has been observed 7–10 years after the initiation of screening (5), about half of that observed in women who are 50–69 years old. Although mammographic sensitivity is indisputably lower (less accurate) in younger women, one expert has asserted (6) that “Nothing magical happens at age 50. There is no significant difference in breast tissue as seen by mammography” when women in their 40s are compared with women in their 50s. Tabar et al. (7) attributed the smaller benefit of screening women in their 40s to shorter sojourn times in some women and to the long interval between screening examinations that occurred in the Two-County Trial. This commentary will give an overview of available information about biologic and life style factors that may reduce the accuracy of screening mammography and thereby also reduce screening efficacy. Among the factors diminishing the efficacy of screening (Table 1), false-negative mammograms are of crucial importance. Delay in the detection of breast cancer must reduce the opportunity to reduce mortality. This conviction led to a study of menstruating women that found that the chances of a woman having a false-negative mammographic examination were almost doubled in the luteal phase of the menstrual cycle compared to what the chances were in the follicular phase, although only in women who had ever used exogenous hormones (presumably oral contraceptives) (8). Possible biologic mechanisms that could explain this observation are increased mammographic density associated with breast tissue changes in the luteal phase and luteal mastalgia (pain) restricting mammographic compression. More recently, White et al. (9) reported a small but statistically significant increase in mammographic density in the luteal phase. This observation is consistent with the increase in falsenegative mammograms previously reported (8), with the conclusion that early breast cancer detection is more difficult to achieve in younger women (10) and with the generally accepted notion that increased density (variously described as mammographic, parenchymal, and fibroglandular) is associated with decreased mammographic sensitivity (Table 2). To identify other factors that may reduce screening efficacy by reducing mammographic accuracy in both premenopausal and postmenopausal women, it may be useful to consider the following issues:
Risk of Cancer by<i>ATM</i>Missense Mutations in the General Population
Authors: Sarah Louise Dombernowsky, Maren Weischer, Kristine Højgaard Allin, Stig Egil Bojesen, Anne Tybjjrg-Hansen, Børge Grønne Nordestgaard
Journal: Journal of Clinical Oncology (2008)

Purpose Truncating and missense mutations in the ATM gene, which cause insufficient DNA damage surveillance, allow damaged cells to proceed into mitosis, which eventually results in increased cancer susceptibility. We tested the hypotheses that ATM Ser49Cys and ATM Ser707Pro heterozygosity increase the risk of cancer overall, of breast cancer, and of 26 other cancer subtypes in the general population. Patients and Methods We genotyped 10,324 individuals from the Danish general population who were observed prospectively for 36 years, during which 2,056 developed cancer. Results Multifactorially adjusted hazard ratios for ATM Ser49Cys heterozygotes versus noncarriers were 1.2 (95% CI, 0.9 to 1.5) for cancer overall, 0.8 (95% CI, 0.3 to 2.0) for breast cancer, 4.8 (95% CI, 2.2 to 11) for melanoma, 2.3 (95% CI, 1.1 to 5.0) for prostate cancer, and 3.4 (95% CI, 1.1 to 11) for cancer of the oral cavity/pharynx. Multifactorially adjusted hazard ratios for ATM Ser707Pro heterozygotes versus noncarriers were 0.8 (95% CI, 0.6 to 1.2) for cancer overall, 0.6 (95% CI, 0.2 to 1.6) for breast cancer, 10 (95% CI, 1.1 to 93) for thyroid/other endocrine tumors, and 2.7 (95% CI, 1.0 to 7.6) for cancer of corpus uteri. Conclusion ATM missense mutations do not increase the risk of cancer overall or of breast cancer in the general population; however, we observed in exploratory analyses that ATM missense mutations may be associated with an increased risk of other cancer subtypes. As we did multiple comparisons, some of these findings could represent chance findings rather than real phenomena.
The effect of bromhexine hydrochloride on the viscoelastic properties of mucus from the mini-pig
Authors: GP Martin, BE Loveday, C Marriott
Journal: European Respiratory Journal (1990)

Mucus was collected daily from open-ended pouches established surgically in three mini-pigs. After a five day control period bromhexine hydrochloride (BHCl) was administered to each pig at dose levels of 0.5, 1.0 and 2.0 mg.kg-1 twice daily for five days. Each study period was followed by a five day washout period, when mucus was collected but no drug given. The viscoelastic properties of each mucus sample were determined using creep compliance analysis. BHCl was shown to reduce the residual shear viscosity (p less than 0.05) and increase the instantaneous shear compliance at all dose levels (p less than 0.005), despite the large inherent intra- and inter-animal variation in the rheological properties of the daily samples. No change was found in the wet weight of the mucus samples throughout any of the study periods. This experimental model would appear to provide a valuable in vivo method of assessing the mucoregulatory potential of administered compounds.
The Efficacy and Safety of Imeglimin as Add-on Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy
Authors: Pascale Fouqueray, Valdis Pirags, Silvio E. Inzucchi, Clifford J. Bailey, Guntram Schernthaner, Michaela Diamant, Harold E. Lebovitz
Journal: Diabetes Care (2012)

A 12-week study assessed the efficacy and safety of a new oral antidiabetic agent, imeglimin, as add-on therapy in type 2 diabetes patients inadequately controlled with metformin alone.A total of 156 patients were randomized 1:1 to receive imeglimin (1,500 mg twice a day) or placebo added to a stable dose of metformin (1,500-2,000 mg/day). Change in A1C from baseline was the primary efficacy outcome; secondary outcomes included fasting plasma glucose (FPG) and proinsulin/insulin ratio.After 12 weeks, the placebo-subtracted decrease in A1C with metformin-imeglimin was -0.44% (P < 0.001). Metformin-imeglimin also significantly improved FPG and the proinsulin/insulin ratio from baseline (-0.91 mg/dL and -7.5, respectively) compared with metformin-placebo (0.36 mg/dL and 11.81). Metformin-imeglimin therapy was generally well-tolerated with a comparable safety profile to metformin-placebo.Addition of imeglimin to metformin improved glycemic control and offers potential as a new treatment for type 2 diabetes.
Methotrexate-related pulmonary complications in rheumatoid arthritis.
Authors: P Barrera, R F Laan, P L van Riel, P N Dekhuijzen, A M Boerbooms, L B van de Putte
Journal: Annals of the Rheumatic Diseases (1994)

Methotrexate (MTX) was described as a drug in 1946' and first used in the treatment of human disease (childhood leukaemia) in 1948.2Successful MTX treatment for rheumatoid arthritis (RA) and psoriasis was reported in 1951,3 although the interest in this drug at that time was probably overshadowed by the impressive results of cortico-steroid treatment until approximately 1980.MTX was approved by the food and drug administration (FDA) for the treatment of severe and dis- abling psoriasis in 1971 and for RA only in 1988.4MTX-related pulmonary toxicity was first observed during treatment of childhood leukaemia in 19695 and later in malig- nancies, psoriasis6 7 and polymyositis.7I Though it was postulated that pulmonary toxicity would appear only with a weekly dose higher than 20 mg,7 this did not prove to be true when in 1983 pneumonitis was also reported during low-dose MTX treatment for RA9 10
"Forward!" The experience of a new guide dog owner
Authors: R. T. Edwards
Journal: BMJ (2002)

Diagnosed at Moorfields Eye Hospital at the age of 4 with retinitis pigmentosa and told that I would not see beyond the age of 15, I have been fortunate to reach the age of 35 with some residual peripheral vision. Not many people appreciate that only 18% of people registered blind can see nothing at all. I have never liked the word “blind,” with its negative connotations in everyday terms such as “blind drunk” and “blind ignorance.” In my line of research, even the term “randomised double blind trial” has left me feeling awkward. However, since I have started walking into walls, opening tins of peaches for our rather surprised cat, and putting my two and a half year old daughter in the bath still wearing her socks, I decided it was time to reassess matters.

Although I have carried a white cane for many years, this has not proved effective in signalling my limited …
Thymic Medullary Epithelial Cell Differentiation, Thymocyte Emigration, and the Control of Autoimmunity Require Lympho–Epithelial Cross Talk via LTβR
Authors: Thomas Boehm, Stefanie Scheu, Klaus Pfeffer, Conrad C. Bleul
Journal: The Journal of Experimental Medicine (2003)

Thymocytes depend on the interaction with thymic epithelial cells for the generation of a diverse, nonautoreactive T cell repertoire. In turn, thymic epithelial cells acquire their three-dimensional cellular organization via instructive signals from developing thymocytes. The nature of these signals has been elusive so far. We show that thymocytes and medullary epithelial cells (MECs) communicate via the lymphotoxin beta receptor (LTbetaR) signaling axis. Normal differentiation of thymic MECs requires LTbetaR ligand on thymocytes and LTbetaR together with nuclear factor-kappaB-inducing kinase (Nik) in thymic epithelial cells. Impaired lympho-epithelial cross talk in the absence of the LTbetaR causes aberrant differentiation and reduced numbers of thymic MECs, leads to the retention of mature T lymphocytes, and is associated with autoimmune phenomena, suggesting an unexpected role for LTbetaR signaling in central tolerance induction.
Effectiveness of publicity campaign encouraging earlier referral of hearing loss in adults.
Authors: R L King, B Barry, D N Brooks
Journal: BMJ (1987)

During 16,070 consultations in general practice 70 adults complained of difficulty with hearing. A simple poster displayed in the waiting areas together with an accompanying leaflet almost doubled the incidence of presentation of loss of hearing. Nevertheless, more than half of those complaining had failed to notice the prominently displayed personally relevant message, and the beneficial effect was lost almost as soon as the poster was removed.
A comprehensive multiattribute system for classifying the health status of survivors of childhood cancer.
Authors: D Feeny, W Furlong, R D Barr, G W Torrance, P Rosenbaum, S Weitzman
Journal: Journal of Clinical Oncology (1992)

PURPOSE A multiattribute health status classification system was devised to describe comprehensively the health status of survivors of childhood cancer. METHODS The system consists of seven attributes: sensation, mobility, emotion, cognition, self-care, pain, and fertility. Three to five levels of functioning are defined for each attribute. Any specific combination of seven attribute levels constitutes a health state. In the first survey, the system was used to classify the health status of 20 children currently undergoing therapy for high-risk acute lymphoblastic leukemia (ALL), Wilms' tumor, or neuroblastoma, and eight who had completed treatment. A second survey consisted of 13 children with brain tumors on active treatment. RESULTS In general, independent ratings by clinicians were in agreement, and consensus was readily achieved in 1 to 2 minutes per patient. Children on therapy experienced a higher burden of morbidity than those off treatment. Brain tumor patients experienced more morbidity than patients in the first survey. CONCLUSION The multiattribute system provides a compact but comprehensive tool for long-term follow-up of survivors of childhood cancer. It captures both multiple sequelae and varying levels of severity. By using a mathematical utility function, a single summary score of health-related quality of life may be assigned to each health state. Additional studies to establish reproducibility, validity, responsiveness, and generalizability are indicated.
An introduction to the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas
Authors: M Ostergaard
Journal: Annals of the Rheumatic Diseases (2005)

This article gives a short overview of the development and characteristics of the OMERACT rheumatoid arthritis MRI scoring system (RAMRIS), followed by an introduction to the use of the EULAR–OMERACT rheumatoid arthritis MRI reference image atlas. With this atlas, MRIs of wrist and metacarpophalangeal joints of patients with rheumatoid arthritis can be scored for synovitis, bone oedema, and bone erosion, guided by standard reference images.
Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer
Authors: August Vidal, Clara Muñoz, María-José Guillén, Jemina Moretó, Sara Puertas, María Martínez-Iniesta, Agnés Figueras, Laura Padullés, Francisco J. García-Rodriguez, Mireia Berdiel-Acer, Miguel A. Pujana, Ramón Salazar, Marta Gil-Martin, Lola Martí, Jordi Ponce, David G. Molleví, Gabriel Capella, Enric Condom, Francesc Viñals, Dori Huertas, Carmen Cuevas, Manel Esteller, Pablo Avilés, Alberto Villanueva
Journal: Clinical Cancer Research (2012)

Epithelial ovarian cancer (EOC) is the fifth leading cause of death in women diagnosed with gynecologic malignancies. The low survival rate is because of its advanced-stage diagnosis and either intrinsic or acquired resistance to standard platinum-based chemotherapy. So, the development of effective innovative therapeutic strategies to overcome cisplatin resistance remains a high priority.To investigate new treatments in in vivo models reproducing EOCs tumor growth, we generated a preclinical model of ovarian cancer after orthotopic implantation of a primary serous tumor in nude mice. Further, matched model of acquired cisplatin-resistant tumor version was successfully derived in mice. Effectiveness of lurbinectedin (PM01183) treatment, a novel marine-derived DNA minor groove covalent binder, was assessed in both preclinical models as a single and a combined-cisplatin agent.Orthotopically perpetuated tumor grafts mimic the histopathological characteristics of primary patients' tumors and they also recapitulate in mice characteristic features of tumor response to cisplatin treatments. We showed that single lurbinectedin or cisplatin-combined therapies were effective in treating cisplatin-sensitive and cisplatin-resistant preclinical ovarian tumor models. Furthermore, the strongest in vivo synergistic effect was observed for combined treatments, especially in cisplatin-resistant tumors. Lurbinectedin tumor growth inhibition was associated with reduced proliferation, increased rate of aberrant mitosis, and subsequent induced apoptosis.Taken together, preclinical orthotopic ovarian tumor grafts are useful tools for drug development, providing hard evidence that lurbinectedin might be a useful therapy in the treatment of EOC by overcoming cisplatin resistance.
Effects of Tamoxifen and Exemestane on Cognitive Functioning of Postmenopausal Patients With Breast Cancer: Results From the Neuropsychological Side Study of the Tamoxifen and Exemestane Adjuvant Multinational Trial
Authors: Christina M. Schilder, Caroline Seynaeve, Louk V. Beex, Willem Boogerd, Sabine C. Linn, Chad M. Gundy, Hilde M. Huizenga, Johan W. Nortier, Cornelis J. van de Velde, Frits S. van Dam, Sanne B. Schagen
Journal: Journal of Clinical Oncology (2010)

To evaluate the influence of adjuvant tamoxifen and exemestane on cognitive functioning in postmenopausal patients with breast cancer (BC).Neuropsychological assessments were performed before the start (T1) and after 1 year of adjuvant endocrine treatment (T2) in Dutch postmenopausal patients with BC, who did not receive chemotherapy. Patients participated in the international Tamoxifen and Exemestane Adjuvant Multinational trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive BC.Participants included 80 tamoxifen users (mean age, 68.7 years; range 51 to 84), 99 exemestane users (mean age, 68.3 years; range, 50 to 82), and 120 healthy controls (mean age, 66.2 years; range, 49 to 86). At T2, after adjustment for T1 performance, exemestane users did not perform statistically significantly worse than healthy controls on any cognitive domain. In contrast, tamoxifen users performed statistically significantly worse than healthy controls on verbal memory (P < .01; Cohen's d = .43) and executive functioning (P = .01; Cohen's d = .40), and statistically significantly worse than exemestane users on information processing speed (P = .02; Cohen's d = .36). With respect to visual memory, working memory, verbal fluency, reaction speed, and motor speed, no significant differences between the three groups were found.After 1 year of adjuvant therapy, tamoxifen use is associated with statistically significant lower functioning in verbal memory and executive functioning, whereas exemestane use is not associated with statistically significant lower cognitive functioning in postmenopausal patients with BC. Our results accentuate the need to include assessments of cognitive effects of adjuvant endocrine treatment in long-term safety studies.
Potassium influx in the frog atrium during the cardiac cycle.
Authors: D F Juncker, P Y Lee, E A Greene, R Stish, V Lorber
Journal: Circulation Research (1975)

A method for measuring inwardly directed transmembrane tracer flow during the cardiac cycle was developed and applied to a study of 42K influx in frog atrial trabeculae. A fine frog atrial fiber was suspended in a stream of nonisotopic perfusate into which a smaller tracer-containing bolus could be injected, subjecting the fiber to a brief, controlled exposure to the tracer at any desired point in the cardiac cycle. In an experiment, the tissue was exposed to a fixed number of radioactive pulses at a selected point in the cardiac cycle; a brief flush with nonradioactive perfusate removed ambient and extracellular label and an extended wash and removed the remaining intracellular tracer for radioassay. The same procedure was repeated at different points in the cycle, and the resulting tracer uptake at each point measured the relative influx of the particular ion. In this way, a characteristic and reproducible 42K influx profile was demonstrated which exhibited a marked drop below diastolic values during the first 500 msec or so of the action potential followed by a rise and an overshoot above resting values. The time of return to the resting level was somewhat uncertain but was tentatively placed in the vicinity of rapid repolarization. We suggest that the rise and the overshoot reflect the activity of the membrane Na+, K+-adenosinetriphosphatase.
Dihydroartemisinin-piperaquine against multidrug-resistant Plasmodium falciparum malaria in Vietnam: randomised clinical trial
Authors: Tran Tinh Hien, Christiane Dolecek, Pham Phuong Mai, Nguyen Thi Dung, Nguyen Thanh Truong, Le Hong Thai, Dong Thi Hoai An, Tran Tan Thanh, Kasia Stepniewska, Nicholas J White, Jeremy Farrar
Journal: The Lancet (2004)
Immunotherapy earns its spot in the ranks of cancer therapy
Authors: Drew Pardoll, Charles Drake
Journal: The Journal of Experimental Medicine (2012)

Since it became clear that all cancer cells express tumor-specific and tumor-selective antigens generated by genetic alterations and epigenetic dysregulation, the immunology community has embraced the possibility of designing therapies to induce targeted antitumor immune responses. The potential therapeutic specificity and efficacy of such treatments are obvious to anyone who studies the exquisite specificity and cytocidal potency of immune responses. However, the value assigned to a therapeutic modality by the oncology community at large does not depend on scientific principle; all that matters is how patients respond. The bar for the ultimate acceptance of a therapy requires more than anecdotal clinical responses; rather, the major modalities of cancer therapeutics, including surgery, chemotherapy, radiation therapy, and, more recently, drugs targeting oncogenes, have earned their place only after producing dramatic frequent clinical responses or demonstrating statistically significant survival benefits in large randomized phase 3 clinical trials, leading to FDA approval. Although tumor-targeted antibodies have certainly cleared this bar, immunotherapies aimed at harnessing antitumor cellular responses have not—until now.
Placebo-Controlled Trial of Sertraline in the Treatment of Binge Eating Disorder
Authors: S L McElroy, L S Casuto, E B Nelson, K A Lake, C A Soutullo, P E Keck, J I Hudson
Journal: American Journal of Psychiatry (2000)

The authors' goal was to assess the efficacy of sertraline in the treatment of binge eating disorder.Thirty-four outpatients with DSM-IV binge eating disorder were randomly assigned to receive either sertraline (N=18) or placebo (N=16) in a 6-week, double-blind, flexible-dose (50-200 mg) study. Except for response level, outcome measures were analyzed by random regression methods, with treatment-by-time interaction as the effect measure.Compared with placebo, sertraline was associated with a significantly greater rate of reduction in the frequency of binges, clinical global severity, and body mass index as well as a significantly greater rate of increase in clinical global improvement. Patients receiving sertraline who completed the study demonstrated a higher level of response, although the effect was not significant.In a 6-week trial, sertraline was effective and well tolerated in the treatment of binge eating disorder.