tbuckley/cabot-search huggingface dataset:
Prospective Breast Cancer Risk Prediction Model for Women Undergoing Screening Mammography
Authors: William E. Barlow, Emily White, Rachel Ballard-Barbash, Pamela M. Vacek, Linda Titus-Ernstoff, Patricia A. Carney, Jeffrey A. Tice, Diana S. M. Buist, Berta M. Geller, Robert Rosenberg, Bonnie C. Yankaskas, Karla Kerlikowske
Journal: JNCI Journal of the National Cancer Institute (2006)

Risk prediction models for breast cancer can be improved by the addition of recently identified risk factors, including breast density and use of hormone therapy. We used prospective risk information to predict a diagnosis of breast cancer in a cohort of 1 million women undergoing screening mammography.There were 2,392,998 eligible screening mammograms from women without previously diagnosed breast cancer who had had a prior mammogram in the preceding 5 years. Within 1 year of the screening mammogram, 11,638 women were diagnosed with breast cancer. Separate logistic regression risk models were constructed for premenopausal and postmenopausal examinations by use of a stringent (P<.0001) criterion for the inclusion of risk factors. Risk models were constructed with 75% of the data and validated with the remaining 25%. Concordance of the predicted with the observed outcomes was assessed by a concordance (c) statistic after logistic regression model fit. All statistical tests were two-sided.Statistically significant risk factors for breast cancer diagnosis among premenopausal women included age, breast density, family history of breast cancer, and a prior breast procedure. For postmenopausal women, the statistically significant factors included age, breast density, race, ethnicity, family history of breast cancer, a prior breast procedure, body mass index, natural menopause, hormone therapy, and a prior false-positive mammogram. The model may identify high-risk women better than the Gail model, although predictive accuracy was only moderate. The c statistics were 0.631 (95% confidence interval [CI] = 0.618 to 0.644) for premenopausal women and 0.624 (95% CI = 0.619 to 0.630) for postmenopausal women.Breast density is a strong additional risk factor for breast cancer, although it is unknown whether reduction in breast density would reduce risk. Our risk model may be able to identify women at high risk for breast cancer for preventive interventions or more intensive surveillance.
Postmarket Surveillance of Medical Devices: A Comparison of Strategies in the US, EU, Japan, and China
Authors: Daniel B. Kramer, Yongtian T. Tan, Chiaki Sato, Aaron S. Kesselheim
Journal: PLoS Medicine (2013)

We evaluated strategies for postmarket surveillance of medical devices in the United States, European Union, Japan, and China.N Each system shares several common elements, including primary reliance on passive adverse event collection for marketed devices, but vary widely in their allocation of stakeholder responsibilities and mechanisms for evaluating the performance and safety of approved devices.N Postmarket surveillance may be improved through greater system transparen- cy, scheduled re-examination of approved devices, and balancing central and local control.
Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients
Authors: Carola H. Schrader, Markus Kolb, Karim Zaoui, Christa Flechtenmacher, Niels Grabe, Klaus-Josef Weber, Thomas Hielscher, Peter K. Plinkert, Jochen Hess
Journal: Molecular Cancer (2015)

Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far. Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis. KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear β-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an independent risk factor for unfavorable clinical outcome. In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT.
Bio‐electrospraying and Cell Electrospinning: Progress and Opportunities for Basic Biology and Clinical Sciences
Authors: Denis Poncelet, Paul de Vos, Nicolai Suter, Suwan N. Jayasinghe
Journal: Advanced Healthcare Materials (2011)

Engineering of functional tissues is a fascinating and fertile arena of research and development. This flourishing enterprise weaves together many areas of research to tackle the most complex question faced to date, namely how to design and reconstruct a synthetic three-dimensional fully functional tissue on demand. At present our healthcare is under threat by several social and economical issues together with those of a more scientific and clinical nature. One such issue arises from our increasing life expectancy, resulting in an ageing society. This steeply growing ageing society requires functional organotypic tissues on demand for repair, replacement, and rejuvenation (R(3) ). Several approaches are pioneered and developed to assist conventional tissue/organ transplantation. In this Progress Report, "non-contact jet-based" approaches for engineering functional tissues are introduced and bio-electrosprays and cell electrospinning, i.e., biotechniques that have demonstrated as being benign for directly handling living cells and whole organisms, are highlighted. These biotechniques possess the ability to directly handle heterogeneous cell populations as suspensions with a biopolymer and/or other micro/nanomaterials for directly forming three-dimensional functional living reconstructs. These discoveries and developments have provided a promising biotechnology platform with far-reaching ramifications for a wide range of applications in basic biological laboratories to their utility in the clinic.
Estrogen Receptor-α Phosphorylated at Ser118 Is Present at the Promoters of Estrogen-Regulated Genes and Is Not Altered Due to HER-2 Overexpression
Authors: Gregory E. Weitsman, Lin Li, George P. Skliris, James R. Davie, Kanyarat Ung, Yulian Niu, Linda Curtis-Snell, Ladislav Tomes, Peter H. Watson, Leigh C. Murphy
Journal: Cancer Research (2006)

Abstract Detection of estrogen receptor (ER)-α phosphorylated at Ser118 (P-Ser118-ER-α) may be an indicator of an intact ligand-dependent ER-α in breast tumors in vivo and may predict responsiveness to endocrine therapy. The current study addresses whether P-Ser118-ER-α is functionally involved in ER target gene transcription and if this is modulated by HER-2 overexpression. Using chromatin immunoprecipitation analysis, P-Ser118-ER-α was found associated with the promoters of several estrogen-regulated genes in MCF-7 breast cancer cells 30 minutes following estrogen treatment. Coactivators AIB1 and p300 were coimmunoprecipitated with P-Ser118-ER-α following estrogen treatment. The overexpression of HER-2 protein in MCF-7 cells did not affect estrogen induction of phosphorylation of Ser118 or its presence at the promoters of several estrogen-regulated genes. U0126, an inhibitor of mitogen-activated protein kinase (MAPK) pathway, had no effect on P-Ser118-ER-α. The lack of effect of HER-2 overexpression on P-Ser118-ER-α expression in cell models is supported by similar levels of expression of P-Ser118-ER-α in ER+/HER-2-overexpressing and ER+/HER-2− breast tumors in vivo. Using inhibitors of cyclin-dependent kinase 7 (Cdk7), [(5,6-dichloro-1-β-d-ribofuranosylbenzimidazole and 2-(R)-1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine], and IκB kinase-α (IKK-α; BAY-11-7082), we show that IKK-α, but not Cdk7, is at least in part involved in estrogen-mediated phosphorylation at Ser118 in MCF-7 cells. Our data provide direct evidence for a functional role of P-Ser118-ER-α in estrogen-regulated signaling and do not support the hypothesis that resistance of breast tumors to tamoxifen therapy involves ligand independent activation of ER-α due to constitutive phosphorylation of Ser118 by constitutive activation of MAPK pathway. (Cancer Res 2006; 66(20): 10162-70)
SULFONAMIDE CHEMOTHERAPY OF COMBINED INFECTION WITH INFLUENZA VIRUS AND BACTERIA
Authors: Carl G. Harford, Mary Ruth Smith, W. Barry Wood
Journal: The Journal of Experimental Medicine (1946)

1. Sulfonamide chemotherapy controls the bacterial component of combined infection with influenza virus and pneumococci in rats. 2. Reinstillation of fluid (broth, physiological salt solution) into the respiratory passages of mice several days after sublethal viral infection converts the viral infection into a lethal one. 3. Sulfonamide chemotherapy controls the bacterial component of combined bacterial and viral infection of mice, produced by intrabronchial inoculation of mixtures of bacteria and sublethal or lethal doses of virus. 4. Bacterial pneumonia may be superimposed upon sublethal viral infection in mice by inhalation of fine droplets of bacterial suspension several days after inoculation of virus. Normal mice inhaling fine droplets of bacterial suspension fail to develop obvious disease. 5. Sulfonamide chemotheiapy controls bacterial pneumonia superimposed on sublethal viral infection by inhalation of fine droplets of bacterial culture. 6. The secondary bacterial penumonia does not convert the sublethal viral infection into a lethal one. 7. If another pandemic of influenza occurs, it is probable that sulfonamide chemotherapy will be valuable in the treatment of secondary bacterial pneumonia and will be effective in lowering the case fatality rate if the viral component of the infection is not severe enough by itself to cause death.
Conserved T Cell Receptor Repertoire in Primary and Memory CD8 T Cell Responses to an Acute Viral Infection
Authors: David J.D. Sourdive, Kaja Murali-Krishna, John D. Altman, Allan J. Zajac, Jason K. Whitmire, Christophe Pannetier, Philippe Kourilsky, Brian Evavold, Alessandro Sette, Rafi Ahmed
Journal: The Journal of Experimental Medicine (1998)

Viral infections often induce potent CD8 T cell responses that play a key role in antiviral immunity. After viral clearance, the vast majority of the expanded CD8 T cells undergo apoptosis, leaving behind a stable number of memory cells. The relationship between the CD8 T cells that clear the acute viral infection and the long-lived CD8 memory pool remaining in the individual is not fully understood. To address this issue, we examined the T cell receptor (TCR) repertoire of virus-specific CD8 T cells in the mouse model of infection with lymphocytic choriomeningitis virus (LCMV) using three approaches: (a) in vivo quantitative TCR β chain V segment and complementarity determining region 3 (CDR3) length repertoire analysis by spectratyping (immunoscope); (b) identification of LCMV-specific CD8 T cells with MHC class I tetramers containing viral peptide and costaining with TCR Vβ–specific antibodies; and (c) functional TCR fingerprinting based on recognition of variant peptides. We compared the repertoire of CD8 T cells responding to acute primary and secondary LCMV infections, together with that of virus-specific memory T cells in immune mice. Our analysis showed that CD8 T cells from several Vβ families participated in the anti-LCMV response directed to the dominant cytotoxic T lymphocyte (CTL) epitope (NP118–126). However, the bulk (∼70%) of this CTL response was due to three privileged T cell populations systematically expanding during LCMV infection. Approximately 30% of the response consisted of Vβ10+ CD8 T cells with a β chain CDR3 length of nine amino acids, and 40% consisted of Vβ8.1+ (β CDR3 = eight amino acids) and Vβ8.2+ cells (β CDR3 = six amino acids). Finally, we showed that the TCR repertoire of the primary antiviral CD8 T cell response was similar both structurally and functionally to that of the memory pool and the secondary CD8 T cell effectors. These results suggest a stochastic selection of memory cells from the pool of CD8 T cells activated during primary infection.
Lung and thorax development during adolescence: relationship with pubertal status
Authors: V. Nève, F. Girard, A. Flahault, M. Boulé
Journal: European Respiratory Journal (2002)

The aim of the present study was to define reference values for lung volumes and the lung transfer factor for carbon monoxide ( T L,CO ) for an adolescent population using thoracic volume index (TVI) and an index of pubertal stage in order to account for the variation in growth pattern between adolescents. TVI, pubertal stage by Tanner scale (PST), time since menarche, functional residual capacity measured using the helium­dilution technique, vital capacity, total lung capacity and T L,CO measured using a steady­state method were determined in 51 males (aged 13–20 yrs; PST T3–T5) and 52 females (aged 13–18 yrs; PST T2–T4; all but three had already undergone menarche). In male adolescents, height, weight, TVI, lung volumes and T L,CO increased with age. This was not the case in female adolescents. In males, the TVI was the independent variable that best correlated with pulmonary volumes. In females, height was the independent variable that best correlated with pulmonary volumes. In both sexes, the variable that best correlated with T L,CO was PST, associated with height in males. This cross­sectional study provides prediction equations for lung volumes and the lung transfer factor for carbon monoxide taking into account thoracic volume index and pubertal stage. It shows that, in adolescent males, lung and thoracic development occurs during and until the end of puberty. Conversely, in adolescent females, lung development is almost finished following menarche.
Association between apolipoprotein E genotype, chronic liver disease, and hepatitis B virus
Authors: Seun Joo Ahn, Dong Kyu Kim, Soon Sun Kim, Chang Bum Bae, Hyo Jung Cho, Han Gyeol Kim, Young Jip Kim, Joo Ho Lee, Hyo Jin Lee, Mi Yeon Lee, Kee Bum Kim, Jin Hee Cho, Sung Won Cho, Jae Youn Cheong
Journal: Clinical and Molecular Hepatology (2012)

Background/Aims Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. Methods This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. Results The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. Conclusions The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls. Keywords: Apolipoprotein E; Hepatitis B virus; Genotype; Liver cirrhosis
Panitumumab Plus FOLFOX4 or Panitumumab Plus Folfiri in Subjects with Wild-Type KRAS (EXON 2) Colorectal Cancer and Multiple or Unresectable Liver-Limited Metastases: Data from the Randomized, Phase II Planet Study
Authors: A. Abad, B. Massutí, C. Grávalos, P. Escudero, C. Guillén-Ponce, L. Layos, M.A. Gomez, M.J. Safont, J. Gallego, J. Sastre, C. Pericay, R. Dueñas, C. López-López, F. Losa, M. Valladares, E. González-Flores, A. Yuste, L. Robles, A. Sáenz, T. Cano, A. Carrato, E. Aranda
Journal: Annals of Oncology (2014)
Address to the Section of Psychology
Authors: T. H. Tuke
Journal: BMJ (1873)

middle of the interval.This "intermediate pain," as Dr. Priestley calls it, may last only a few (lays, or it may cointinue and increase in severity till the next menstruation, the only interval of ease being for the first tenl or twlelve days after menstruation.MIenstruation in these cases is often irregular, generally retarded, sometirmies it comes too soon, and in some cases, a whole month may be passed over, but the pain occurs when the menstruation is due, even thotugh the discharge does not appear.The discharge is generally scanty, hut sometime.sit is excesssive.Its appearance i-s almost always preceded or followed by severe headache, often by vomiting, and, during its flow, nalpitation is often complained of, also frequenlt micturition, anid sometimes tenesmuis and klneading in the rectum.Miss H. states that menstruation has always bcen Tainful during the fit st two or thlee hours, hut for the last two or tlhree years she has suffered very rmuch fromn.pain for a week before menstruation begins, and at tlle sarne tiine her breasts have also become very painful.She has had muchi palpitation lately, anid severe headaches before menstruation begins.MIrs.V., married seveii years, no clhildren, states that menstruation w%vas always painful att the beginning-, but, sinice marriage, slhe hias stffered for a week before it begins, from pain round the sides, stomach, and back, and fr-om pain in her breasts, wlhich become swollen.About five years ago, the os ttteri was slit, after wlhicih she became pregnant, hut aborted at the end of the third month.The painful menstrttation continiues, notwithstanding the operation and pregnanicy.These were cases in which the form of dysmenorrlhea, of w7hich I now speak, supervelled on that due to obstruction; oni examination, in this latter case, the utetus zwas found normal in position and size.Tihe os anid cer-vix were quite healtlhy, but the os was very open in consequence of the operation that had been performed on it.The rig,ht ovary, however, was founid to be swollen, anid very tenider to the totlch.In many cases, in addition to the symptoms already described, there is a conistant dull, aching, sickening, pain in the back ; and there is so much pain, in coitzh, that all attempts at intercourse lhave to be given up.Mlrs.C. has been married ten years, and has no family.For many years she has had painful menstruation, the pain beginning more than a week beforehand.The os uteri was twice slit, without in any way relieving the pain of menstruation.Slhe has also had the orifice of the vagina dilated, for the pain in coitiz, hut without benefit.On examilna- tion, the vagina admitted a full sized speculum with ease; there was nio contraction or spasm at the orifice.The uterus was found with the cervix slit, but otherwise lhealthy, and the right ovary was fouLnd lying in Douglas' space, somewlhat enilarged and tender to the touiclh, the pain, on pressure oln it, being of the same clharacter as that caused by ilnter- course.
Basic and clinical electrophysiology of pulmonary vein ectopy
Authors: J de Bakker
Journal: Cardiovascular Research (2002)

In a subset of patients, atrial fibrillation is caused by rapidly firing foci that are often located in the pulmonary veins especially when fibrillation is paroxysmal. Histologic data show that myocardial tissue of the left atrial wall extends into the pulmonary venous walls. Both in dog and human pulmonary veins, arrangement of the myofibers is complex. Clinical and animal studies reveal both double potentials and fractionated electrograms in the pulmonary veins, which are related to the complex architecture of the myocardial sleeves in the veins. Such a structure supports the occurrence of reentry. As well, the reduced coupling of cells at sites with abrupt changes in fiber direction could facilitate the escape of a focus and subsequent activation of surrounding tissue. Intracellular recordings made in the pulmonary veins of guinea pig and dog hearts showed that spontaneous activity can occur. Spontaneous action potentials with phase 4 depolarization as well as early after depolarizations were observed in these animal models. In non-spontaneously active preparations, spontaneous activity could be provoked by pharmacologic interventions. The cycle length of bursts of ectopic beats arising in the pulmonary veins of man is often irregular, supporting a focal mechanism of the ectopic beats. The anisotropic characteristics of the myocardial sleeves in the veins may increase the ability of a focus to become evident.
What Is the Sensitivity and Specificity of Self-Report for Retinopathy Screening?
Authors: Elizabeth A. Walker, Patricia A. Zybert, Charles E. Basch
Journal: Diabetes Care (2002)

A wide range in screening rates for diabetic retinopathy by dilated ophthalmic examination has been reported in studies over the last decade (1–4). Comparisons of these rates should take into account the measure used to assess the condition (i.e., screened versus unscreened). Examples of measures include self-report by the individual, claims data for the service, or medical record abstraction of the desired information. Because goals for improvement of diabetes care (5) are based on studies using these reported rates, the sources of these data must be considered and described. Self-report by an individual relies on memory, correct discernment of a dilated versus undilated exam, and accurate identification of the screening behavior within the time frame in question. Claims data, on the other hand, can overestimate the rate of dilated exams under the code for a comprehensive ophthalmic examination. Furthermore, depending on the patient’s health care coverage plan, the retinopathy screening may be a service that does not require a separate claim. Finally, abstraction of medical records may be a sensitive measure for a dilated ophthalmic examination; however, its specificity is dependent on a record system that captures and organizes the medical reports for retrieval and evaluation.

A recently published study by Basch et al. (6) reported that a telephone-based health education intervention was associated with a …