tbuckley/cabot-search huggingface dataset:
Association Between Child Poverty and Academic Achievement
Authors: Youssef Oulhote, Philippe Grandjean
Journal: JAMA Pediatrics (2015)

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Targeting CDK4 and CDK6: From Discovery to Therapy
Authors: Charles J. Sherr, David Beach, Geoffrey I. Shapiro
Journal: Cancer Discovery (2015)

Biochemical and genetic characterization of D-type cyclins, their cyclin D-dependent kinases (CDK4 and CDK6), and the polypeptide CDK4/6 inhibitor p16(INK4)over two decades ago revealed how mammalian cells regulate entry into the DNA synthetic (S) phase of the cell-division cycle in a retinoblastoma protein-dependent manner. These investigations provided proof-of-principle that CDK4/6 inhibitors, particularly when combined with coinhibition of allied mitogen-dependent signal transduction pathways, might prove valuable in cancer therapy. FDA approval of the CDK4/6 inhibitor palbociclib used with the aromatase inhibitor letrozole for breast cancer treatment highlights long-sought success. The newest findings herald clinical trials targeting other cancers.Rapidly emerging data with selective inhibitors of CDK4/6 have validated these cell-cycle kinases as anticancer drug targets, corroborating longstanding preclinical predictions. This review addresses the discovery of these CDKs and their regulators, as well as translation of CDK4/6 biology to positive clinical outcomes and development of rational combinatorial therapies.
BAG-1: A Novel Biomarker Predicting Long-Term Survival in Early-Stage Breast Cancer
Authors: Bruce C. Turner, Stanislaw Krajewski, Maryla Krajewska, Shinichi Takayama, Andrew A. Gumbs, Darryl Carter, Timothy R. Rebbeck, Bruce G. Haffty, John C. Reed
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Among women with early-stage breast cancer treated with lumpectomy and radiation therapy, 30% to 40% will develop metastatic disease, which is often fatal. A need exists therefore for biomarkers that distinguish patients at high risk of relapse. We performed a retrospective correlative analysis of BAG-1 protein expression in breast tumors derived from a cohort of early-stage breast cancer patients. PATIENTS AND METHODS: Archival paraffin blocks from 122 women with stages I to II breast cancer treated with lumpectomy and radiation therapy (median follow-up, 12.1 years) were analyzed by immunohistochemical methods using monoclonal antibodies recognizing BAG-1 and other biomarkers, including Bcl-2, estrogen receptor, progesterone receptor, p53, and HER2/Neu. Immunostaining data were correlated with distant metastasis-free survival (DMFS) and overall survival (OS). RESULTS: Cytosolic immunostaining for BAG-1 was upregulated in 79 (65%) of 122 invasive breast cancers (P &lt; .001) compared with normal breast. Elevated BAG-1 was significantly associated with longer DMFS and OS, overall (stages 1 and II) and in node-negative (stage I only) patients, on the basis of univariate and multivariate analyses (DMFS, P = .005; OS, P = .01, in multivariate analysis of all patients; DMFS, P = .005; OS, P = .001, in multivariate analysis of node-negative patients). All other biomarkers failed to reach statistical significance in multivariate analysis. Clinical stage was an independent predictor of OS (P = .04) and DMFS (P = .02). CONCLUSION: These findings provide preliminary evidence that BAG-1 represents a potential marker of improved survival in early-stage breast cancer patients, independent of the status of axillary lymph nodes.
Rethinking bioequivalence and equivalence requirements of orally inhaled drug products
Authors: Dina Al-Numani, Philippe Colucci, Murray P. Ducharme
Journal: Asian Journal of Pharmaceutical Sciences (2015)

Orally inhaled drug products (OIPs), such as corticosteroids and bronchodilators, are at the forefront of asthma and chronic obstructive pulmonary disease treatments, two diseases that afflict worldwide populations. Introducing generics of these products is essential, as the pricing of these medications remain a barrier to adequate patient care. Currently, there is no consensus between regulatory bodies as to the bioequivalence and equivalence requirements of OIPs that are intended for local action in the lungs. This manuscript critically reviews these requirements and presents future directions for clinicians, scientists, and regulators to consider to optimize the development and approval of OIPs.
Plasma kidney injury molecule‐1 in heart failure: renal mechanisms and clinical outcome
Authors: Johanna E. Emmens, Jozine M. ter Maaten, Yuya Matsue, Marco Metra, Christopher M. O'Connor, Piotr Ponikowski, John R. Teerlink, Gad Cotter, Beth Davison, John G. Cleland, Michael M. Givertz, Daniel M. Bloomfield, Howard C. Dittrich, John Todd, Dirk J. van Veldhuisen, Hans L. Hillege, Kevin Damman, Peter van der Meer, Adriaan A. Voors
Journal: European Journal of Heart Failure (2015)
Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics
Authors: Carlo Sala Frigerio, Bart De Strooper
Journal: Annual Review of Neuroscience (2016)

Ten years of remarkable progress in understanding the fundamental biochemistry of Alzheimer's disease have been followed by ten years of remarkable and increasing clinical insight into the natural progression of the disorder. The concept of a long, intermediary, prodromal phase between the first appearance of amyloid plaques and tangles and the manifestation of dementia is now well established. The major challenge for the next decade is to chart the many cellular processes that underlie this phase and link the biochemical alterations to the clinical manifestation of Alzheimer's disease. We discuss here how genetics, new cell culture systems, and improved animal models will fuel this work. We anticipate that the resulting novel insights will provide a basis for further drug development for this terrible disease.
Concurrent epidemics of influenza A/H3N2 and A/H1N1pdm in Southern China: A serial cross-sectional study
Authors: Chunli Wu, Maggie Haitian Wang, Xing Lu, Ka Chun Chong, Jason He, Chun-Yip Yau, Mark Hui, Xiaowen Cheng, Li Yang, Benny Chung-Ying Zee, Renli Zhang, Ming-Liang He
Journal: Journal of Infection (2015)
Abstract 15569: Video-Only Cardiopulmonary Resuscitation Education for Families Before Hospital Discharge: A Multicenter Pragmatic Clinical Trial
Authors: Audrey L Blewer, Jiaqi Li, Marion Leary, Lance B Becker, Barbara J Riegel, Mary E Putt, Judy A Shea, James N Kirkpatrick, Robert A Berg, Vinay M Nadkarni, Peter W Groeneveld, Benjamin S Abella
Journal: Circulation (2015)

Background: The need for improved dissemination of public cardiopulmonary resuscitation (CPR) education is highlighted by the fact that bystander CPR is delivered in less than 40% of cardiac arrests in the US. Studies have suggested that simplified methods for CPR training can promote broader dissemination. The minimum CPR training curriculum to encourage broad implementation but ensure long-term retention remains poorly characterized. Objectives: To compare video-only CPR training without a manikin to training with a video self-instruction (VSI) kit including a practice manikin. We hypothesized that laypersons who receive video-only training will perform comparable chest compressions (CC) as those taught with a VSI kit six months after initial training. Methods: We performed a pragmatic, randomized trial of CPR training for family members of cardiac patients on inpatient wards at eight hospitals. Hospitals were block randomized to offer either video-only training or the VSI kit to high-risk families before patient discharge. At six months post-training, CPR skills were assessed quantitatively. We analyzed the mean difference in chest compression rate and depth between cohorts and used multivariate regression modeling to control for confounding. Results: From 2/2012 to 5/2015, 1610 subjects were enrolled and 571 subjects consented to a 6-month skills check. Enrollees’ mean age was 52±15 years, 73% were female and 81% were immediate patient’s family. The unadjusted mean CC rate in the video-only cohort was 88 (95% CI: 85, 90) compressions per min (cpm) and 89 (95% CI: 87, 91) cpm in the VSI cohort (p=0.56), while the mean CC depth was 40 (95% CI: 39, 42) mm in the video-only cohort and 45 (95% CI: 44, 47) mm in the VSI cohort (p&lt;0.01). The statistical relationship remained the same after adjustment for confounding. Conclusions: To our knowledge, this represents the largest prospective trial of CPR training and long-term retention among lay providers. Video-only training yielded a statistically indistinguishable difference in CC rate compared to VSI training. While the CC depth was statistically different, the clinical impact of these differences may be small given recent clinical research suggesting maximum survival benefit at depths between 40-55 mm.
Abstract 16740: Impact of Diastolic Dysfunction on Outcomes of Patients With Aortic Stenosis
Authors: Romain Capoulade, Abdellaziz Dahou, Marie-Annick Clavel, Jean G Dumesnil, Lionel Tastet, Marie Arsenault, Elisabeth Bedard, Philippe Pibarot
Journal: Circulation (2014)

BACKGROUND: Left ventricular (LV) diastolic dysfunction (DD) is frequent in patients with aortic stenosis (AS). However, its impact on the prognosis of these patients is not well known. The objective of this study was to assess the impact of DD on mortality in a large cohort of AS patients. METHODS: 895 consecutive patients (70±13 y.o., 58% men) with AS (52% severe) were included in this study. Diastolic function was graded into 4 classes: Normal, Grade I: abnormal relaxation, Grade II: pseudo-normal; Grade III: restrictive. RESULTS: Among the 895 patients included in this study, 19 (2%) had normal diastolic function, 498 (56%) had Grade I, and 274 (30%) had Grade II, and 104 (12%) had Grade III. During a mean follow-up of 5.5±3.7 years, 436 patients died, including 309 from cardiovascular (CV) causes. Survival was similar among groups with no DD, Grade I, and Grade II. However, 8-year survival of patients with Grade III DD (36 ±5%) was significantly lower than that of the patients in the 3 other groups (...
Comment on Hoffstad et al. Diabetes, Lower-Extremity Amputation, and Death. Diabetes Care 2015;38:1852–1857
Authors: Luigi Uccioli, Laura Giurato, Marco Meloni, Valentina Izzo, Valeria Ruotolo, Roberto Gandini, Benjamin Lipsky
Journal: Diabetes Care (2015)

We have read with interest the article by Hoffstad et al. (1), as lower-extremity amputation (LEA) is a topic in which we have had a long-standing interest (2,3). Thus, we would like to share some of our thoughts about its findings.

This article focuses its attention on the large increase in the incidence of death among patients with diabetes who underwent a LEA, as has been previously reported by several authors, including ourselves (1,3). This article further highlights the incomplete relationship between mortality and known diabetic complications, such as cardiovascular disease or renal insufficiency, and suggests that the presence of other unspecified factor(s) may be …
Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation
Authors: Jonathan P. Piccini, Anne S. Hellkamp, Jeffrey B. Washam, Richard C. Becker, Günter Breithardt, Scott D. Berkowitz, Jonathan L. Halperin, Graeme J. Hankey, Werner Hacke, Kenneth W. Mahaffey, Christopher C. Nessel, Daniel E. Singer, Keith A.A. Fox, Manesh R. Patel
Journal: Circulation (2015)

Background— Patients with atrial fibrillation (AF) often take multiple medications. Methods and Results— We examined characteristics and compared adjusted outcomes between rivaroxaban and warfarin according to number of concomitant baseline medications and the presence of combined cytochrome P450 3A4 and P-glycoprotein inhibitors in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study. At baseline, 5101 patients (36%) were on 0 to 4 medications, 7298 (51%) were on 5 to 9, and 1865 (13%) were on ≥10. Although polypharmacy was not associated with higher risk of stroke or non–central nervous system embolism (adjusted hazard ratio, 1.02 for ≥10 versus 0–4 medications; 95% confidence interval, 0.76–1.38), it was associated with higher risks of the combined end point of stroke, non–central nervous system embolism, vascular death, or myocardial infarction (adjusted hazard ratio, 1.41 for ≥10 versus 0–4 medications; 95% confidence interval, 1.18–1.68) and nonmajor clinically relevant or major bleeding (adjusted hazard ratio, 1.47 for ≥10 versus 0–4 medications; 95% confidence interval, 1.31–1.65). There was no significant difference in primary efficacy (adjusted interaction P =0.99) or safety outcomes (adjusted interaction P =0.87) between treatment groups by number of medications. Patients treated with 0 to 4 medications had lower rates of major bleeding with rivaroxaban (adjusted hazard ratio, 0.71; 95% confidence interval, 0.52–0.95; interaction P =0.0074). There was no evidence of differential outcomes in those treated with ≥1 combined cytochrome P450 3A4 and P-glycoprotein inhibitors. Conclusions— In a population of patients with atrial fibrillation, two thirds were on ≥5 medications. Increasing medication use was associated with higher risk of bleeding but not stroke. Rivaroxaban was tolerated across complex patients on multiple medications. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00403767.
Diabetic Amyotrophy
Authors: D. R. Redwood
Journal: BMJ (1962)

B^m 521 a pungent smell and which does not produce an opalescent solution when poured into water.However, accurate information coveiing the use of potent bacteri- cides could be given to barbers during their period of instruction at the trade school.Much confusion exists in the lay mind regarding the multiplication of bacteria on the surface of inanimate objects, and it is doubtful if any significant increase in numbers takes place on many surfaces.With metals of known toxicity, the number of viable cells may actually decrease.Immersing an infected instrument in a solution having feeble bacteriostatic activity cannot prevent the spread of infection, and, since staphylococcal skin sepsis is common, it seems not unreasonable to ensure that active bactericides are used by barbers to prevent further spread of infection within the community. SummaryA bacteriological survey of 197 barbers' shops is described, and the incidence of infection with Staph.pyogenes is recorded.The degree of contamination amongst individual instruments is noted, together with the antibiotic sensitivity and bacteriophage type of the' strains isolated.Attention is drawn to the relatively feeble activity of the antiseptic solutions commonly in use, and recommendations are made for the use of potent bactericides to reduce the dissemination of pathogenic staphylococci.We are indebted to Dr. Philip Woodruff.Director-General of Public Health, whose interest and co-operation made this investigation possible.
Diltiazem Treatment for Pre-Clinical Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers
Authors: Carolyn Y. Ho, Neal K. Lakdawala, Allison L. Cirino, Steven E. Lipshultz, Elizabeth Sparks, Siddique A. Abbasi, Raymond Y. Kwong, Elliott M. Antman, Christopher Semsarian, Arantxa González, Begoña López, Javier Diez, E. John Orav, Steven D. Colan, Christine E. Seidman
Journal: JACC Heart Failure (2014)
Corrigendum to “Design and validation of a diagnostic score for biliary atresia” [J Hepatol 2014;61:116–123]
Authors: Mohamed Abdel-Salam El-Guindi, Mostafa Mohamed Sira, Ahmad Mohamed Sira, Tahany Abdel-Hameed Salem, Hatem Abdel-Sattar Konsowa, Alif Abdel-Hakim Allam
Journal: Journal of Hepatology (2015)
In utero fetal liver hematopoietic stem cell transplantation: is there a role for alloreactive T lymphocytes?
Authors: Maria Concetta Renda, Emanuela Fecarotta, Aurelio Maggio, Francesco Dieli, Guido Sireci, Alfredo Salerno, Lola Markling, Magnus Westgren, Gianfranca Damiani, Cristina Jakil, Francesco Picciotto
Journal: Blood (2000)
Combination prophylaxis for prevention of maternal-infant HIV transmission. Beyond 076 [editorial]
Authors: Shaffer N
Journal: JAMA (2001)

This editorial focuses on the study by Mandelbrot et al. which provides a systematic evaluation on the efficacy and toxicity of combination HIV prophylaxis during pregnancy.  The study evaluates the addition of lamivudine to the standard 076 zidovudine regimen with lamivudine administration beginning at 32 weeks gestation in the mother and lamivudine administration to the newborn for 6 weeks.  The study design is a historical comparison with a previous national cohort of HIV-infected pregnant women who had received the 076 regimen.  A randomized trial was not conducted because of the belief among participating clinicians that the combination therapy would be superior to zidovudine monotherapy. In developed countries additional interventions that enhance the 076 regimen such as combination lamivudine-zidovudine and zidovudine plus cesarean delivery offer the possibility of virtually eliminating perinatal HIV transmission.  Barriers to this goal include identifying and offering prophylaxis to all HIV-positive pregnant women in prenatal care and providing effective interventions for HIV-infected women who present in labor.
Clinical Relevance of Myocardial Injury After Transcatheter Aortic Valve Replacement ∗
Authors: William F. Fearon, Alan C. Yeung
Journal: Journal of the American College of Cardiology (2015)

Every cardiac intervention is fraught with the potential complication of myocardial injury or infarction. The prognostic importance of myocardial injury related to percutaneous coronary intervention and coronary artery bypass grafting has been well documented [(1,2)][1]. After valvular heart surgery
Abberations in bilateral breast cancer
Authors: Ashleen Shadeo, Jennifer Kennett, Teresa Mastracci, Irene Andrulis, Wan Lam
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2963 

Introduction: 0.7% of women diagnosed with breast cancer will develop a second primary cancer and, this scenario is called Bilateral Breast Cancer (BiBC). It has been reported that BiBC accounts for 2-11% of all breast cancer cases. BiBC has the greatest concordance with familial history and early onset of disease occurrence. Mutations in known genes such as BRCA1 , BRCA2 , TP53 , PTEN and CHEK2 account for one third of the hereditary breast cancer cases thus leaving the majority of the genetic culprits unidentified.

Genetic instability is a characteristic of malignant cells. Paired organs, such as the breast, offer a unique opportunity to study the genetic causal events in breast cancer such that the cells that become malignant in both primary occurrences are identical in terms of original genetic make-up and exposure to environmental factors. Removing these variables will facilitate the discovery of genetic mechanisms that lead to the development of breast cancer. Recently, several groups have preliminarily investigated both familial and sporadic BiBC disease using low-resolution technology thus identifying large regions of chromosomal alteration ranging from several megabases to entire chromosomal arms, which encompass a large number of genes.    >Hypothesis: Comparison of somatic genetic alterations in matched bilateral breast tumours and matched normal tissue will allow us to distinguish the discrete causal events from the random genetic changes that are associated with genetic instability in tumours. Relevant alterations would appear in both sets of tumours and would suggest a role in disease development.    >Results: In this study, we use a whole genome tiling resolution array CGH platform (SMRT aCGH), which allows for breakpoint detection at approximately 80 kb resolution, to identify discrete regions of genetic alterations in ten pairs of BiBC. Genes within regions of alteration that are common to the first and second occurrence groups are assessed for downstream expression effects using the Affymetrix HuU133 plus 2.0 platform. A subset of cases have been further evaluated for copy number variation in the human population without cancer.    >Conclusion: We have identified commonly altered regions in bilateral specimens and have corrleated the genes within these loci to expression patterns which may be valuable in defining the subset of patients who need to be monitored more carefully after the first malignancy.
Multiplex Diagnosis of Oncogenic Fusion and MET Exon Skipping by Molecular Counting Using Formalin-Fixed Paraffin Embedded Lung Adenocarcinoma Tissues
Authors: Kuniko Sunami, Koh Furuta, Koji Tsuta, Shinji Sasada, Takehiro Izumo, Takashi Nakaoku, Yoko Shimada, Motonobu Saito, Hiroshi Nokihara, Shun-ichi Watanabe, Yuichiro Ohe, Takashi Kohno
Journal: Journal of Thoracic Oncology (2015)
Pelvic intra-arterial mitomycin C infusion in previously treated patients with metastatic, unresectable, pelvic colorectal cancer and angiographic determination of tumor vascularity.
Authors: M H Tseng, H C Park
Journal: Journal of Clinical Oncology (1985)

Thirty patients with unresectable pelvic tumors from recurrent or metastatic colorectal cancer, after failing all conventional chemotherapy or radiotherapy, were treated with mitomycin C (MMC) regional intra-arterial (IA) infusion. MMC at a dose of 20 mg/m2 in 100 mL of 5% dextrose in water was infused for a one-hour period through the regional artery (eg, hypogastric, gluteal) approached percutaneously via the femoral artery. This treatment was repeated every four to eight weeks. Of the 26 patients who could be evaluated, three had objective responses, 14 had tumor stabilization, and nine had no response. Median survival time for the responders (Rs) was 435 days, for stabilized patients (Ss) was 263 days, and for nonresponders (NRs) was 195 days, giving an overall survival time of 239 days. Fourteen patients (2 Rs, 8 Ss, and 4 NRs) had good relief of pain after the IA infusion. Thirty-three pelvic arteriograms (including three patients who had never received IA infusion) showed an avascular tumor of grade 0 in eight patients, a hypovascular tumor of grades 1 and 2 in 16 patients, and a vascular tumor of grade 3 in nine patients. Neovasculatures were mainly derived from the hypogastric artery or its branches (eg, gluteal, obturator, and pudendal artery), and occasionally were found to be derived from the superior hemorrhoidal, lumbar, and sacral arteries. The major side effect after the pelvic infusion was necrotizing cellulitis occurring in the buttock. Myelosuppression was manageable and other toxic effects were mild. Metastatic colorectal cancer occurring in the pelvis was basically a vascular-deficient tumor. Regional IA MMC infusion given intermittently was found effective in palliating pelvic pain and improving the quality of these patients' lives.