tbuckley/cabot-search huggingface dataset:
Is the Breast Cancer Mortality Decrease in Sweden Due to Screening or Treatment? Not the Right Question
Authors: N. Segnan, S. Rosso, A. Ponti
Journal: JNCI Journal of the National Cancer Institute (2012)

screening. In the presence of stable or increasing incidence trends, better treatment is the obvious candidate of this success story. Its synergistic effect with screening has been modeled under different assumptions, taking into account that screening can reduce the rate of death from breast cancer only when followed by treatment (5). Not only is mammography screening likely to have detected breast cancers at earlier stages, allowing the adoption of less harmful and more effective treatments, but also the presence of an organized screening program may have promoted the provision of more effective care by monitoring the treatment quality of screen-detected cancers and by favoring the creation of multidisciplinary units of breast cancer specialists (6). Efforts to disentangle the effects of organized screening, early diagnosis, and treatment based on descriptive population data are therefore unlikely to be a reliable exercise, also because screening itself is intrinsically part of clinical practice (7). In our opinion, it is time to move beyond an apparently never-ending debate (8–10) about the extent to which screening for breast cancer in the 1970s to 1990s has reduced mortality from breast cancer—as if it was isolated from the rest of health care. The current scenario is completely different from the past: asymptomatic patients with screen-detected breast cancers represent a large proportion of the breast cancer patients in developed countries. Current priorities should be to increase the accuracy of breast cancer screening and the appropriateness and availability of treatment, to improve communication, and to advance research. In the European Union, member states have been encouraged (11) to extend breast cancer screening programs to the entire target population, to monitor the quality of the screening process, and to link screening, diagnosis, and treatment in a comprehensive framework of quality-assured health care. Recognition of the merits and limitations of breast cancer screening, as well as of its clinical management, should help design more mature and evidence-based communication with the public and with individuals. In terms of research, the identification of indolent cancers that may be candidates for no or less aggressive treatment, the recognition of clues on how to safely reduce the intensity of screening in low-risk women, and the development of more accurate screening technology would be important steps forward that would be likely to have a large impact on future practice. These improvements would allow lowering the harms, in primis overdiagnosis and overtreatment, and increasing the benefits
Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer
Authors: Qiong Wu, Michèle J Hoffmann, Florian H Hartmann, Wolfgang A Schulz
Journal: Molecular Cancer (2005)

Amplifications at 6p22.3 are prevalent in advanced stage bladder cancer (TCC). Previous studies have identified SOX4, CDKAL, and E2F3 as targets of this amplification and therefore potential oncogenes, but the more telomeric DEK gene too has been reported as overexpressed and amplified. We have therefore investigated whether the intermediate region harboring the oncogene candidate ID4 is also part of the amplicon.Expression of E2F3, DEK, and ID4 was investigated by real-time RT-PCR in 28 TCC compared to 6 normal bladder tissues and in 15 TCC cell lines compared to cultured normal urothelial cells. Expression of E2F3 as well as DEK increased on average in tumor vs. normal tissues (3-fold and 2.5-fold, resp.), but only the increase for E2F3 was statistically significant (p = 0.039). ID4 overexpression was observed in selected specimens. Each of the three genes was overexpressed in several cell lines, up to 150-fold (ID4), 30-fold (E2F3), and 9-fold (DEK), but these increases were not correlated to each other. Instead, moderate (DEK) to excellent (ID4) correlations were observed with copy number increases of microsatellites near each gene. Microsatellite copy number increases were highly heterogeneous across the investigated several Mb region revealing at least three subregions of amplification.Extending previous reports, our data indicate that the 6p22.3 amplicon in TCC is highly heterogeneous and targets several genes in a variable fashion. Among these, expression of E2F3 and DEK appear to be generally increased in TCC, with additional increases caused by amplifications. In contrast, over-expression of ID4, which is normally predominantly expressed in testes and brain, appears to depend more strictly on gene amplification. Accordingly, the effect of amplifications at 6p22.3 in bladder cancer is expected to be non-uniform, thereby contributing to the highly variable biological and clinical behavior of advanced stage tumors. ID4 is a potential oncogene in a small subset of bladder cancers.
Frail Patients Are at Increased Risk for Mortality and Prolonged Institutional Care After Cardiac Surgery
Authors: Dana H. Lee, Karen J. Buth, Billie-Jean Martin, Alexandra M. Yip, Gregory M. Hirsch
Journal: Circulation (2010)

Background— Frailty is an emerging concept in medicine yet to be explored as a risk factor in cardiac surgery. Where elderly patients are increasingly referred for cardiac surgery, the prevalence of a frail group among these is also on the rise. We assessed frailty as a risk factor for adverse outcomes after cardiac surgery. Methods and Results— Functional measures of frailty and clinical data were collected prospectively for all cardiac surgery patients at a single center. Frailty was defined as any impairment in activities of daily living (Katz index), ambulation, or a documented history of dementia. Of 3826 patients, 157 (4.1%) were frail. Frail patients were older, were more likely to be female, and had risk factors for adverse surgical outcomes. By logistic regression, frailty was an independent predictor of in-hospital mortality (odds ratio 1.8, 95% CI 1.1 to 3.0), as well as institutional discharge (odds ratio 6.3, 95% CI 4.2 to 9.4). Frailty was an independent predictor of reduced midterm survival (hazard ratio 1.5, 95% CI 1.1 to 2.2). Conclusions— Frailty is a risk for postoperative complications and an independent predictor of in-hospital mortality, institutional discharge, and reduced midterm survival. Frailty screening improves risk assessment in cardiac surgery patients and may identify a subgroup of patients who may benefit from innovative processes of care.
Elimination of hepatitis C virus by short term NS3-4A and NS5B inhibitor combination therapy in human hepatocyte chimeric mice
Authors: Eiji Ohara, Nobuhiko Hiraga, Michio Imamura, Eiji Iwao, Naohiro Kamiya, Ichimaro Yamada, Tomohiko Kono, Mayu Onishi, Daizaburo Hirata, Fukiko Mitsui, Tomokazu Kawaoka, Masataka Tsuge, Shoichi Takahashi, Hiromi Abe, C. Nelson Hayes, Hidenori Ochi, Chise Tateno, Katsutoshi Yoshizato, Shinji Tanaka, Kazuaki Chayama
Journal: Journal of Hepatology (2010)
Barriers to Cadaveric Renal Transplantation Among Blacks, Women, and the Poor
Authors: G. Caleb Alexander
Journal: JAMA (1998)

Context.-Cadaveric renal transplantation rates differ greatly by race, sex, and income.Previous efforts to lessen these differences have focused on the transplant waiting list.However, the transplantation process involves a series of steps related to medical suitability, interest in transplantation, pretransplant workup, and movement up a waiting list to eventual transplantation.Objective.-Todetermine the relative importance of each step in explaining differences in cadaveric renal transplantation rates.Design.-Prospective cohort study. Setting andPatients.-Atotal of 7125 patients beginning long-term dialysis between January 1993 and December 1996 in Indiana, Kentucky, and Ohio.Main Outcome Measures.-Completion of 4 separate steps during each patient-year of follow-up: (A) being medically suitable and possibly interested in transplantation; (B) being definitely interested in transplantation; (C) completing the pretransplant workup; and (D) moving up a waiting list and receiving a transplant.Results.-Compared with whites, blacks were less likely to complete steps B (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.61-0.76),C (OR, 0.56; 95% CI, 0.48-0.65),and D (OR, 0.50; 95% CI, 0.40-0.62)after adjustment for age, sex, cause of renal failure, years receiving dialysis, and median income of patient ZIP code.Compared with men, women were less likely to complete each of the 4 steps, with ORs of 0.90, 0.89, 0.80, and 0.82, respectively.Poor individuals were less likely than wealthy individuals to complete steps A, B, and C, with ORs of 0.67, 0.78, and 0.77, respectively.Conclusions.-Barriers at several steps are responsible for sociodemographic differences in access to cadaveric renal transplantation.Efforts to allocate kidneys equitably must address each step of the transplant process.
Induction of leptin resistance through direct interaction of C-reactive protein with leptin
Authors: Ke Chen, Fanghong Li, Ji Li, Hongbo Cai, Steven Strom, Alessandro Bisello, David E Kelley, Miriam Friedman-Einat, Gregory A Skibinski, Mark A McCrory, Alexander J Szalai, Allan Z Zhao
Journal: Nature Medicine (2006)
Mycophenolate mofetil in autoimmune and inflammatory skin disorders
Authors: Hossein C. Nousari, Alexander Sragovich, Arash Kimyai-Asadi, Diane Orlinsky, Grant J. Anhalt
Journal: Journal of the American Academy of Dermatology (1999)

Mycophenolate mofetil (MMF) has been widely used as an immunosuppressant in organ transplantation. MMF has recently been added to therapeutic regimens for skin disorders. Expanding the use of MMF in dermatology, we describe additional patients with autoimmune and inflammatory skin diseases, including 4 cases of pemphigus vulgaris, 1 case of pemphigus foliaceus, 1 case of perineal and metastatic cutaneous Crohn's disease, 1 case of bullous pemphigoid and psoriasis, and 1 case of psoriasis. Most of these patients had refractory disease or had developed significant side effects to conventional therapy, including azathioprine, methotrexate, prednisone, cyclosporine, acitretin, PUVA, UVB, and tacrolimus. MMF was effective and well tolerated in all these patients. The dosages of MMF ranged from 500 mg twice daily (for psoriasis and Crohn's disease) to 1250mg twice daily (for 3 of 4 patients with pemphigus vulgaris). MMF is an effective and relatively safe immunosuppressant in autoimmune and inflammatory skin diseases.
C-Reactive Protein Levels, Variation in the C-Reactive Protein Gene, and Cancer Risk: The Rotterdam Study
Authors: Claire Siemes, Loes E. Visser, Jan-Willem W. Coebergh, Ted A.W. Splinter, Jacqueline C.M. Witteman, André G. Uitterlinden, Albert Hofman, Huibert A.P. Pols, Bruno H.Ch. Stricker
Journal: Journal of Clinical Oncology (2006)

It remains unclear if inflammation itself may induce cancer, if inflammation is a result of tumor growth, or a combination of both exists. The aim of this study was to examine whether C-reactive protein (CRP) levels and CRP gene variations were associated with an altered risk of colorectal, lung, breast, or prostate cancer.A total of 7,017 participants age > or = 55 years from the Rotterdam Study were eligible for analyses. Mean follow-up time was 10.2 years. High-sensitivity CRP measurements were performed to identify additional values of 0.2 to 1.0 mg/L compared with standard procedures. Genotypes of the CRP gene were determined with an allelic discrimination assay.High levels (> 3 mg/L) of CRP were associated with an increased risk of incident cancer (hazard ratio, 1.4; 95% CI, 1.1 to 1.7) compared with persons with low levels (< 1 mg/L), even after a potential latent period of 5 years was introduced. Although CRP seems to affect several cancer sites, the association was strongest for lung cancer (hazard ratio, 2.8; 95% CI, 1.6 to 4.9). A CRP single nucleotide polymorphism associated with decreased CRP levels was associated with an increased lung cancer risk of 2.6 (95% CI, 1.6 to 4.4) in homozygous carriers.Baseline CRP levels seem to be a biomarker of chronic inflammation preceding lung cancer, even after subtracting a 5-year latent period. Furthermore, CRP gene variation associated with low CRP blood levels was relatively common in patients with lung cancer. Both chronic inflammation and impaired defense mechanisms resulting in chronic inflammation might explain these results.
Polyploid Speciation Did Not Confer Instant Reproductive Isolation in Capsella (Brassicaceae)
Authors: T. Slotte, H. Huang, M. Lascoux, A. Ceplitis
Journal: Molecular Biology and Evolution (2008)

Polyploid formation is a major mode of sympatric speciation in flowering plants. Unlike other speciation processes, polyploidization is often assumed to confer instant reproductive isolation. Shared polymorphism across ploidy levels has therefore often been attributed to multiple polyploid origins, whereas the alternative hypothesis of introgressive hybridization has rarely been rigorously tested. Here, we sequence 12 nuclear loci representing 6 genes duplicated by polyploidy in 92 accessions of the tetraploid Capsella bursa-pastoris together with the corresponding loci in 21 accessions of its close diploid relative Capsella rubella. In C. bursa-pastoris accessions from western Eurasia, where the 2 species occur in partial sympatry, we find higher levels of nucleotide diversity than in accessions from eastern Eurasia, where C. rubella does not grow. Furthermore, haplotypes are shared across ploidy levels at 4 loci in western but not in eastern Eurasia. We test whether haplotype sharing is due to retention of ancestral polymorphism or due to hybridization and introgression using a coalescent-based isolation-with-migration model. In western but not in eastern Eurasia, there is evidence for unidirectional gene flow from C. rubella to C. bursa-pastoris. An independent estimate of the timing of dispersal of C. bursa-pastoris to eastern Eurasia indicates that it probably predated introgression. Our results show that polyploid speciation need not result in immediate and complete reproductive isolation, that postpolyploidization hybridization and introgression can contribute significantly to genetic variation in a newly formed polyploid, and that divergence population genetic analysis constitutes a powerful way of testing hypotheses on polyploid speciation.
DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4·5 h of symptom onset (PRE-FLAIR): a multicentre observational study
Authors: Götz Thomalla, Bastian Cheng, Martin Ebinger, Qing Hao, Thomas Tourdias, Ona Wu, Jong S Kim, Lorenz Breuer, Oliver C Singer, Steven Warach, Soren Christensen, Andras Treszl, Nils D Forkert, Ivana Galinovic, Michael Rosenkranz, Tobias Engelhorn, Martin Köhrmann, Matthias Endres, Dong-Wha Kang, Vincent Dousset, A Gregory Sorensen, David S Liebeskind, Jochen B Fiebach, Jens Fiehler, Christian Gerloff
Journal: The Lancet Neurology (2011)
Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study
Authors: Alexandria T Phan, Daniel M Halperin, Jennifer A Chan, David R Fogelman, Kenneth R Hess, Paige Malinowski, Eileen Regan, Chaan S Ng, James C Yao, Matthew H Kulke
Journal: The Lancet Oncology (2015)
<i>PIK3CA</i> Mutations Are Associated With Lower Rates of Pathologic Complete Response to Anti–Human Epidermal Growth Factor Receptor 2 (HER2) Therapy in Primary HER2-Overexpressing Breast Cancer
Authors: Sibylle Loibl, Gunter von Minckwitz, Andreas Schneeweiss, Stefan Paepke, Annika Lehmann, Mahdi Rezai, Dirk M. Zahm, Peter Sinn, Fariba Khandan, Holger Eidtmann, Karel Dohnal, Clemens Heinrichs, Jens Huober, Berit Pfitzner, Peter A. Fasching, Fabrice Andre, Judith L. Lindner, Christos Sotiriou, August Dykgers, Sanxing Guo, Stephan Gade, Valentina Nekljudova, Sherene Loi, Michael Untch, Carsten Denkert
Journal: Journal of Clinical Oncology (2014)

Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer, with mutations in PIK3CA being the most common. This study investigated the association between PIK3CA genotype and pathologic complete response (pCR) rates in human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either dual or single anti-HER2 treatment in addition to neoadjuvant chemotherapy.PIK3CA mutations in 504 tumor samples from participants in the neoadjuvant GeparQuattro, GeparQuinto, and GeparSixto studies were evaluated. All HER2-positive patients received either trastuzumab or lapatinib or the combination plus anthracycline-taxane chemotherapy. PIK3CA mutations were evaluated in formalin-fixed, paraffin-embedded tissues from core biopsies with a tumor cell content of ≥ 20% by using classical Sanger sequencing of exon 9 and exon 20.Overall, 21.4% of the patients harbored a PIK3CA mutation. Detection of a PIK3CA mutation was significantly associated with a lower pCR rate (19.4% with PIK3CA mutation v 32.8% with PIK3CA wild-type; odds ratio [OR], 0.49; 95% CI, 0.29 to 0.83; P = .008). In the 291 hormone receptor (HR) -positive tumors, pCR rate was 11.3% with a PIK3CA mutation compared with 27.5% with PIK3CA wild-type (OR, 0.34; 95% CI, 0.15 to 0.78; P = .011). In 213 patients with HR-negative tumors, pCR rate was 30.4% with PIK3CA mutation and 40.1% without (OR, 0.65; 95% CI, 0.32 to 1.32; P = .233; interaction test P = .292). In multivariable analysis, HR status and PIK3CA status provided independent predictive information. In patients with PIK3CA mutation, the pCR rates were 16%, 24.3%, and 17.4% with lapatinib, trastuzumab, and the combination, respectively (P = .654) and in the wild-type group, they were 18.2%, 33.%, and 37.1%, respectively (P = .017). Disease-free survival and overall survival were not statistically significantly different between patients with mutant and wild-type PIK3CA.HER2-positive breast carcinomas with a PIK3CA mutation are less likely to achieve a pCR after neoadjuvant anthracycline-taxane-based chemotherapy plus anti-HER2 treatment, even if a dual anti-HER2 treatment is given.
Does Neoadjuvant/Adjuvant Chemotherapy Change the Natural History of Classic Invasive Lobular Carcinoma?
Authors: Artur Katz
Journal: Journal of Clinical Oncology (2005)

on a retrospective analysis of the role of primary chemotherapy in patients with invasive lobular carcinoma of the classic type (ILC). Based on the presented data, these patients tended to have a statistically significant higher stage and an increased chance of lymph node involvement at diagnosis, as well as a significant higher frequency of hormone-responsive disease and lower nuclear grade. These patients had significant lower rates of pathologic complete response (3% v 15%; P .001) andahigherincidenceofresiduallymphnodedisease( four positive lymph nodes, 41% v 26%; P .001) after neoadjuvant chemotherapy and, based on our current knowledge, were expected to have had a much worse outcome. 2-4 However, as pointed out by the authors, the oppositehasoccurred.Chaturvedietalhavealsorecently reported similar data regarding the effectiveness of neoadjuvant chemotherapy in invasive lobular carcinoma. 5
MCP-1 Gene Activation Marks Acute Kidney Injury
Authors: Raj Munshi, Ali Johnson, Edward D. Siew, T. Alp Ikizler, Lorraine B. Ware, Mark M. Wurfel, Jonathan Himmelfarb, Richard A. Zager
Journal: Journal of the American Society of Nephrology (2010)

Monocyte chemoattractant protein 1 (MCP-1) mediates acute ischemic and toxic kidney injury, but whether this can be used as a biomarker of acute kidney injury (AKI) is unknown. We obtained kidney and urine samples from mice with intrarenal (maleate), prerenal (endotoxemia), or postrenal (ureteral obstruction) injury. We also studied the independent effects of uremia without concomitant kidney injury by performing bilateral ureteral transection in mice. Additionally, we obtained urine samples from APACHE II-matched critically ill patients with or without advancing azotemia (n = 10 in each group). We assayed selected samples for MCP-1, MCP-1 mRNA, and for an activating histone mark (H3K4m3) at urinary fragments of the MCP-1 gene and contrasted the results with those obtained for neutrophil gelatinase-associated lipocalin (NGAL), a comparator "AKI biomarker" gene. Maleate increased urinary MCP-1 protein and mRNA more than the corresponding increases in NGAL. Endotoxemia and ureteral obstruction also increased NGAL and MCP-1 gene expression. Uremia, in the absence of renal injury, induced the NGAL gene, but not MCP-1, suggesting the possibility of better specificity of MCP-1 for AKI. Clinical assessments supported the utility of MCP-1 as a biomarker (e.g., nonoverlapping concentrations of urinary MCP-1 in patients with and without AKI). Elevated levels of urinary MCP-1 mRNA and levels of H3K4m3 at the MCP-1 gene supported MCP-1 gene activation in patients with renal injury. In conclusion, these data suggest that MCP-1 has potential as a biomarker of AKI and provide "proof of concept" that urinary histone assessments provide mechanistic insight among patients with kidney disease.
Triple Versus Dual Antiplatelet Therapy After Coronary Stenting
Authors: Seung-Whan Lee, Seong-Wook Park, Myeong-Ki Hong, Young-Hak Kim, Bong-Ki Lee, Jong-Min Song, Ki Hoon Han, Cheol Whan Lee, Duk-Hyun Kang, Jae-Kwan Song, Jae-Joong Kim, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2005)
Instructions and Reinforcement in the Modification of Neurotic Behavior
Authors: STEWART AGRAS, HAROLD LEITENBERG, DAVID H. BARLOW, LAURENCE E. THOMSON
Journal: American Journal of Psychiatry (1969)

Two simple variables, instruction and reinforcement, were found to modify chronic neurotic behavior. During the experimental procedure precise control of long-established symptomatic behavior was demonstrated. Findings suggest that behavior to be changed by psychotherapy must be precisely defined and exact techniques introduced to change it. To the authors, the experimental method described here appears to be feasible and useful in psychotherapy research.
Improvement in scalp hair growth in androgen‐deficient women treated with testosterone: a questionnaire study
Authors: R.L. Glaser, C. Dimitrakakis, A.G. Messenger
Journal: British Journal of Dermatology (2011)

Androgens are thought to have an adverse effect on female scalp hair growth. However, our clinical experience of androgen replacement therapy in women with androgen deficiency, in which hair loss was seldom reported, led us to question this concept.To evaluate the effect of subcutaneous testosterone therapy on scalp hair growth in female patients.A total of 285 women, treated for a minimum of 1year with subcutaneous testosterone implants for symptoms of androgen deficiency, were asked to complete a survey that included questions on scalp and facial hair. Age, body mass index (BMI) and serum testosterone levels were examined.Out of the 285 patients, 76 (27%) reported hair thinning prior to treatment; 48 of these patients (63%) reported hair regrowth on testosterone therapy (responders). Nonresponders (i.e. no reported hair regrowth on therapy) had significantly higher BMIs than responders (P=0·05). Baseline serum testosterone levels were significantly lower in women reporting hair loss prior to therapy than in those who did not (P=0·0001). There was no significant difference in serum testosterone levels, measured 4weeks after testosterone implantation, between responders and nonresponders. No patient in this cohort reported scalp hair loss on testosterone therapy. A total of 262 women (92%) reported some increase in facial hair growth.Subcutaneous testosterone therapy was found to have a beneficial effect on scalp hair growth in female patients treated for symptoms of androgen deficiency. We propose this is due to an anabolic effect of testosterone on hair growth. The fact that no subject complained of hair loss as a result of treatment casts doubt on the presumed role of testosterone in driving female scalp hair loss. These results need to be confirmed by formal measurements of hair growth.