tbuckley/cabot-search huggingface dataset:
A genome-wide approach to link genotype to clinical outcome by utilizing next generation sequencing and gene chip data of 6,697 breast cancer patients
Authors: Lőrinc Pongor, Máté Kormos, Christos Hatzis, Lajos Pusztai, András Szabó, Balázs Győrffy
Journal: Genome Medicine (2015)

The use of somatic mutations for predicting clinical outcome is difficult because a mutation can indirectly influence the function of many genes, and also because clinical follow-up is sparse in the relatively young next generation sequencing (NGS) databanks. Here we approach this problem by linking sequence databanks to well annotated gene-chip datasets, using a multigene transcriptomic fingerprint as a link between gene mutations and gene expression in breast cancer patients. The database consists of 763 NGS samples containing mutational status for 22,938 genes and RNA-seq data for 10,987 genes. The gene chip database contains 5,934 patients with 10,987 genes plus clinical characteristics. For the prediction, mutations present in a sample are first translated into a 'transcriptomic fingerprint' by running ROC analysis on mutation and RNA-seq data. Then correlation to survival is assessed by computing Cox regression for both up- and downregulated signatures. According to this approach, the top driver oncogenes having a mutation prevalence over 5 % included AKT1, TRANK1, TRAPPC10, RPGR, COL6A2, RAPGEF4, ATG2B, CNTRL, NAA38, OSBPL10, POTEF, SCLT1, SUN1, VWDE, MTUS2, and PIK3CA, and the top tumor suppressor genes included PHEX, TP53, GGA3, RGS22, PXDNL, ARFGEF1, BRCA2, CHD8, GCC2, and ARMC4. The system was validated by computing correlation between RNA-seq and microarray data (r2 = 0.73, P < 1E-16). Cross-validation using 20 genes with a prevalence of approximately 5 % confirmed analysis reproducibility. We established a pipeline enabling rapid clinical validation of a discovered mutation in a large breast cancer cohort. An online interface is available for evaluating any human gene mutation or combinations of maximum three such genes ( http://www.g-2-o.com ).
Role of Donor Immunocompetent Cells in Allograft Rejection 2
Authors: Barbara B. Jacobs, Louise Leonard, Richard C. Parks
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Role of Donor Immunocompetent Cells in Allograft Rejection Get access Barbara B. Jacobs, Barbara B. Jacobs Search for other works by this author on: Oxford Academic PubMed Google Scholar Louise Leonard, Louise Leonard Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard C. Parks Richard C. Parks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 2, August 1976, Pages 345–348, https://doi.org/10.1093/jnci/57.2.345 Published: 01 August 1976 Article history Received: 20 October 1975 Accepted: 20 February 1976 Published: 01 August 1976
VATS Versus Open Surgery for Lung Cancer Resection: Moving Toward a Minimally Invasive Approach
Authors: Jacob Klapper, Thomas A. D’Amico
Journal: Journal of the National Comprehensive Cancer Network (2015)

The use of video-assisted thoracoscopic surgery (VATS) has become the standard approach for the surgical resection of early-stage lung cancer. Although no large prospective, randomized, controlled trial has compared VATS lobectomy with thoracotomy, well-designed retrospective studies have consistently shown that VATS has comparable oncologic outcomes and is associated with fewer complications, reduced length of hospital stay, improvement in patient quality of life, and superior tolerance of adjuvant therapies.
Total Androgen Blockade with Zoladex plus Flutamide vs. Zoladex Alone in Advanced Prostatic Carcinoma: Interim Report of a Multicenter, Double-Blind, Placebo-Controlled Study
Authors: R.O. Fourcade, G. Cariou, P. Coloby, P. Colombel, C. Coulange, P. Grise, P. Mangin, J.Y. Soret
Journal: European Urology (1990)
Physical activity in daily life: A new outcome to evaluate young adult survivors of bronchopulmonary dysplasia?
Authors: Riany De Sousa Sena, Geneviève Tremblay, Norah MacMillan, Taivassalo Tanja, Bourbeau Jean, Jennifer Landry
Journal: European Respiratory Journal (2013)

Background: Bronchopulmonary Dysplasia (BPD) is considered one of the most common chronic lung diseases in children. Interestingly, recent evidence has suggested important similarities between COPD and BPD regarding lung function impairments, but evidence on the extra-pulmonary complications of BPD is still lacking. Therefore, this study aims to evaluate the profile of physical activity in daily life (PADL) in young adults survivors of BPD and compare it with public guidelines for PA. Methods: This is a substudy of a large cohort study being conducted in the province of Quebec, Canada; investigating the long term consequences of adults who were born prematurely between 1993 and 1997. Study participants were submitted to assessments of lung function (spirometry); maximal and submaximal exercise capacity (incremental peak and endurance cycling test), as well as PADL using an activity monitor (SenseWear Armband) for one week. Results: Preliminary results of this study include 11 subjects with BPD (mean (SD): age, 22.5 (1.6) yrs; BMI: 26.5 (8.5) kgm2; gestational age, 27.9 (3.6) weeks; birth weight, 1.12 (0.5kg); FEV%pred: 75(6.8) %pred. In addition, results from activity monitoring showed that BPD subjects in this study walked an average of of 8500 (3596) steps/day and spent 127 (94) minutes in activities of moderate intensity (>3METS). Conclusion: Our results suggest that young adults survivors of BPD are insufficiently active in daily life according to guidelines recommendations of performing at least 150 minutes of moderate PA or walking a minimum of 10000 steps/day. Hence, PADL may be an interesting outcome to evaluate subjects with BPD and may not be overlooked.
Osteogenic/Angiogenic Dual Growth Factor Delivery Microcapsules for Regeneration of Vascularized Bone Tissue
Authors: Ramesh Subbiah, Mintai Peter Hwang, Se Young Van, Sun Hee Do, Hansoo Park, Kangwon Lee, Sang Heon Kim, Kyusik Yun, Kwideok Park
Journal: Advanced Healthcare Materials (2015)

Growth factors (GFs) are major biochemical cues for tissue regeneration. Herein, a novel dual GF delivery system is designed composed of poly(lactic‐ co ‐glycolic acid) (PLGA) nanoparticles (NPs) and alginate microcapsules (MCs) via an electrodropping method. While bone morphogenetic protein (BMP)‐2 is encapsulated in the PLGA NPs, vascular endothelial growth factor (VEGF) is included in the alginate MCs, where BMP‐2‐loaded PLGA NPs are entrapped together in the fabrication process. The initial loading efficiencies of BMP‐2 and VEGF are 78% ± 3.6% and 43% ± 1.7%, respectively. When our dual GF‐loaded MCs are assessed for in vitro osteogenesis of umbilical cord blood‐derived mesenchymal stem cells (UCB‐MSCs) on 2D and 3D environment, MCs contribute to much better UCB‐MSCs osteogenesis as confirmed by von Kossa staining, immunofluorescence (osteocalcin, collagen 1), calcium content measurement, and osteogenic markers expression. In addition, when dual GF‐encapsulated MCs are combined with collagen and then applied to 8 mm diameter rat calvarial defect model, the positive effects on vascularized bone regeneration are much more pronounced; micro computed tomography (CT) and histology analyses exhibit 82.3% bone healing coupled with 12.6% vessel occupied area. Put together, current study indicates a synergistic effect of BMP‐2/VEGF and highlights the great potential of dual GF delivery modality (PLGA NPs‐in‐MC) for regeneration of vascularized bone.
Endotoxin-responsive sequences control cachectin/tumor necrosis factor biosynthesis at the translational level.
Authors: J Han, T Brown, B Beutler
Journal: The Journal of Experimental Medicine (1990)

The biosynthesis of cachectin/TNF is largely regulated at a post-transcriptional level. Bacterial endotoxin, which strongly induces cachectin/TNF production, thus seems to elicit at least some of its effects by altering the macrophage cytoplasmic milieu. It has previously been shown that the 3'-untranslated TTATTTAT element present in numerous cytokines and proto-oncogenes is capable of repressing the translation of mRNA molecules in which it is represented. Using constructs in which the CAT coding sequence is followed by varying segments of the cachectin/TNF 3'-untranslated region, we now demonstrate that downstream sequences present in the cachectin/TNF mRNA are sufficient to mediate greater than 200-fold induction of CAT synthesis in response to activation by endotoxin. Induction of CAT activity is not attributable to a change in cytoplasmic mRNA concentration, but to a marked enhancement of translational efficiency. The response to endotoxin represents "derepression," and is conferred chiefly by the translationally repressive TTATTTAT element, acting in concert with essential flanking sequences.
Growth of Mouse Mammary Glands After Neonatal Sex Hormone Treatment&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Y Tomooka, H A Bern
Journal: JNCI Journal of the National Cancer Institute (1982)

Mammary gland growth was examined in female mice immediately and during 1 month after neonatal treatment with sex hormones. BALB/c mice were given daily injections of hormones for the first 5 days after birth. As a criterion of growth, the number of ductal branchings was counted in stained wholemounts of the fourth (inguinal) pair of glands. At day 6, the growth of the glands was significantly inhibited in animals treated with 17 beta-estradiol (E) or diethylstilbestrol (DES); after treatment with progesterone (P) or androgens, no immediate effect was evident. At day 33, neonatal treatment with E stimulated growth, as did neonatal treatment with testosterone (T) or 5 alpha-dihydrotestosterone (5 alpha-DHT); treatment with a high dose of DES inhibited growth. Treatment with P or 5 beta-dihydrotestosterone had no effect. In conclusion, neonatal treatment with sex hormones has two distinct effects on the growth of mouse mammary gland: 1) inhibition by estrogens, observed immediately after treatment, and 2) stimulation by E, T, and 5 alpha-DHT, observed 4 weeks after treatment.
Abstract 16386: Genome-Wide Association Study of Native Platelet Function in African Americans
Authors: Rehan Qayyum, Lewis C Becker, Diane M Becker, Lisa R Yanek, Suzanne M Leal, Rasika Mathias, Bhoom Suktitipat, Paul F Bray
Journal: Circulation (2011)

Background: We have previously shown that platelet aggregation, an essential component of pathogenesis of acute coronary syndromes, has higher heritability in African Americans than Caucasians. How...
Cerebellar metastases: diagnostic and management considerations.
Authors: C Fadul, K E Misulis, R G Wiley
Journal: Journal of Clinical Oncology (1987)

Prompted by several unsatisfactory outcomes, we reviewed the records of 59 patients with cerebellar metastases (26 solitary) with respect to clinical presentation, diagnosis, and natural history. Eighty-seven percent of patients initially complained of headache, gait disturbance, and/or dizziness. At time of diagnosis, 92% of patients with solitary cerebellar metastases and 74% of the overall series complained of headache and/or difficulty walking. In three of four cases, magnetic resonance imaging (MRI) was superior to x-ray computed tomography (CT) in detecting the cerebellar lesions. Several patients acutely deteriorated during evaluation or at the initiation of radiation therapy. We conclude that a cancer patient presenting with headache and gait difficulty with or without nausea/vomiting and dizziness should promptly undergo head CT scanning, and that MRI is useful even if CT is negative. In addition, we recommend that patients with documented cerebellar metastases receive high-dose glucocorticoid therapy for 48 to 72 hours before beginning radiation therapy. The presence of symptomatic hydrocephalus or failure to respond to glucocorticoids initially are particularly ominous features that may be best managed by early neurosurgical consultation before beginning radiation therapy.
A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.
Authors: P J Loehrer, L H Einhorn, P J Elson, E D Crawford, P Kuebler, I Tannock, D Raghavan, R Stuart-Harris, M F Sarosdy, B A Lowe
Journal: Journal of Clinical Oncology (1992)

PURPOSE A prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma. PATIENTS AND METHODS From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. RESULTS As expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Response rates were superior for the M-VAC regimen compared with single-agent cisplatin (39% v 12%; P less than .0001). Similarly, the progression-free survival (10.0 v 4.3 months) and overall survival (12.5 v 8.2 months) were significantly greater for the combined therapy arm. CONCLUSION Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.
Predictors of poor outcome in chronic thromboembolic pulmonary hypertension
Authors: Congyou Liu, Zhenguo Zhai, Yuanhua Yang, Tuguang Kuang, Wanmu Xie, Chen Wang
Journal: European Respiratory Journal (2012)

Background : Clinical and plasma biomarkers are essential to predict the outcome of pulmonary arterial hypertension (PAH). These markers might also be useful to evaluate the outcome of chronic thromboembolic pulmonary hypertension (CTEPH).   Objective:  Assess the cumulative mortality and identify predictors of the patients with CTEPH.   Methods:  108 patients with CTEPH who registered in Beijing chaoyang hospital between January 2006 and October 2011 were analyzed. The primary endpoint is death, and the second endpoint is worsen of WHO functional class.   Results : During the follow-up period (4-58 months), 11 patients died (10.2%), meanwhile WHO functional class of 4 patients was worsen (3.7%). The 1-,3-year survival rates were respectively 95.1% and 82.1%. BMI (HR 0.798; 95% CI,0.677 to 0.941; P=0.007), leukocyte(HR 1.346; 95% CI,1.145 to 1.582;P   Conclusion : Patients with CTEPH have a better survival rate than patients with PAH. BMI, inflammatory markers (leukocyte, ESR), hemodynamic parameters (CO,PVR) were associated with poor prognosis of patients with CTEPH.
Comparison of Zotarolimus-Eluting Stents With Sirolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization
Authors: Duk-Woo Park, Young-Hak Kim, Sung-Cheol Yun, Soo-Jin Kang, Seung-Whan Lee, Cheol-Whan Lee, Seong-Wook Park, In-Whan Seong, Jae-Hwan Lee, Seung-Jea Tahk, Myung-Ho Jeong, Yangsoo Jang, Sang-Sig Cheong, Joo-Young Yang, Do-Sun Lim, Ki-Bae Seung, Jei-Keon Chae, Seung-Ho Hur, Sang-Gon Lee, Junghan Yoon, Nae-Hee Lee, Young-Jin Choi, Hyun-Sook Kim, Kee-Sik Kim, Hyo-Soo Kim, Taeg-Jong Hong, Hun-Sik Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2010)
Cutaneous features of pseudoxanthoma elasticum in a patient with generalized arterial calcification of infancy due to a homozygous missense mutation in the<i>ENPP1</i>gene
Authors: Q. Li, W. Schumacher, D. Jablonski, D. Siegel, J. Uitto
Journal: British Journal of Dermatology (2012)

Pseudoxanthoma elasticum (PXE) manifests with cutaneous lesions consisting of yellowish papules coalescing into plaques of inelastic skin. Histopathology demonstrates accumulation of pleiomorphic elastic structures with progressive mineralization. The classic form of PXE is caused by mutations in the ABCC6 gene.A 2-year-old patient with PXE of the neck, inguinal folds and lower abdomen, and with extensive tissue mineralization, was evaluated for the underlying mutations in candidate genes known to be involved in ectopic mineralization disorders.The patient's genotype was studied by sequencing ABCC6, MGP and ENPP1 genes, encoding proteins which harbour mutations in ectopic mineralization disorders.No pathogenetic mutations were found in the ABCC6 or MGP genes. Sequencing of ENPP1 disclosed a homozygous missense mutation, p.Y513C, associated with generalized arterial calcification of infancy.This study demonstrates the presence of the cutaneous features of PXE in a genetically distinct disease, generalized arterial calcification of infancy, and thus expands the spectrum of PXE-related disorders.
Lymphoid Neoplasms in Chicken Flocks Free of Infection With Exogenous Avian Tumor Viruses&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: L B Crittenden, R L Witter, W Okazaki, P E Neiman
Journal: JNCI Journal of the National Cancer Institute (1979)

More than 4,500 breeding female chickens of nine inbred lines maintained under specific-pathogen-free conditions to approximately 500 days of age were studied. Routine monitoring and special assays indicated that they were free of infection by exogenous viruses of the leukosis-sarcoma and the reticuloendotheliosis groups. Some birds were maintained free of Marek's disease (MD) virus infection in plastic isolators, and others were maintained in conventional chicken houses and vaccinated with the herpesvirus of turkeys to prevent the lesions of MD. Ten birds bearing lymphoid tumors were observed in two sublines of one line of chickens known to produce embryos that spontaneously produce Rous-associated virus, type 0 (RAV-O), an endogenous virus of the chicken. Four tumors were found in chickens of one subline maintained free of MD virus infection in isolators. These tumors did not involve the bursa and had some histologic features different from those typical of lymphoid leukosis. Six tumors were found in chickens of the other subline that were vaccinated to prevent MD; these tumors involved the bursa and were typical of lymphoid leukosis but not MD. These results suggest that two types of tumors may have been observed. The fact that DNA extracted from both types of tumors did not contain exogenous lymphoid leukosis virus sequences confirms the virologic evidence that exogenous viruses were not involved. The fact that endogenous viral sequences were not increased in copy number suggests that the endogenous virus RAV-O did not directly induce the tumors. Two birds with tumors not involving the bursa were found alive, and transplantable lymphoid tumors were developed. These tumors were of T-cell origin rather than of bursa cell origin as would be expected of lymphoid leukosis. These are the first reported lymphoid tumors that have been observed in the absence of known exogenous tumor virus infection in chickens. Our evidence suggests that the endogenous virus RAV-O did not play a primary role in the induction of these tumors.
A Simple Approach to Reducing Inappropriate Use of Central Venous Catheters
Authors: Deborah Grady
Journal: JAMA Internal Medicine (2015)

unintended consequences due to these in-office payment reduction policies through shifting the performance of these procedures to the hospital environment, with the associated hospital outpatient department payment formula, at a substantial increase in cost to the CMS.White and Wu 2 have examined Medicare hospital cost reports for the period 1996-2009 and concluded that Medicare price cuts yield revenue reductions that are even larger than the Medicare payment reductions-in other words, other payers also reduce payments and affect downstream revenues.In addition, Wu and Shen 3 have demonstrated that drastic reductions in Medicare payments can potentially have an adverse effect on quality of patient care.Lindrooth and colleagues 4 studied 30-day mortality from Medicare databases for the years 1997, 2001, and 2005 and have reported an inverse relationship between changes in profitability and mortality across 21 service lines.Many would view that it is speculative to suggest that reducing payments will lead to an adverse effect on quality of care, but the analyses of Wu et al and Lindrooth et al at least beg the question of whether better strategies for imaging cost containment could be implemented by the CMS.The current health care delivery challenges and resultant changes to the practice landscape demand creative and workable solutions to meet the needs of new practice models as well as help current private practitioners maintain viability while simultaneously promoting high value in health care delivery.These changes include a renewed focus on new payment models, education around evolving models of care, developing and using quality tools to ensure evidence-based care, and promoting the appropriate use of stretched resources.In particular, addressing the problem of overuse of unnecessary tests and procedures by implementing payment models that encourage appropriate testing while discouraging inappropriate testing is a more rational approach for controlling Medicare costs than across-the-board decreases in reimbursement.Physicians will need to assume leadership in new delivery systems and health care policy to encourage all specialties to practice cost-effective medicine.We agree with Fuchs and Milstein 5 : "There is not much that physicians can do directly to change the behavior of insurance companies, employers, or other stakeholders, but physicians are the most influential element in health care.The public's trust in them makes physicians the only plausible catalyst of policies to accelerate diffusion of costeffective care."
Cytokines and Fas regulate apoptosis in murine renal interstitial fibroblasts.
Authors: A Ortiz, C Lorz, S González-Cuadrado, R Garcia del Moral, F O'Valle, J Egido
Journal: Journal of the American Society of Nephrology (1997)

Renal fibrosis is characterized by an increased number of fibroblasts and excessive deposition of extracellular matrix. Apoptotic cell death is a physiological mechanism to limit cell numbers, and an insufficient rate of death may contribute to fibroblast accumulation. However, little is known about the regulation of renal fibroblast survival. The authors have studied the interaction of cytokines and the Fas receptor in the regulation of apoptosis of renal fibroblasts and have observed that murine renal fibroblasts express Fas and the Fas ligand. Tumor necrosis factor alpha (TNFalpha) and agonistic anti-Fas antibodies induce apoptosis of renal fibroblasts in a time- and dose-dependent manner. Serum contains survival factors for renal fibroblasts. Both serum deprivation and TNFalpha increase the sensitivity to Fas-induced death and the expression of fas mRNA and Fas receptor. By contrast, insulin-like growth factor-1 decreases apoptosis induced by both serum deprivation and Fas activation and partially prevents the increase in Fas receptor expression induced by serum deprivation. Murine renal fibroblasts express constitutively both fas ligand mRNA and cell-surface Fas ligand, but the authors could not demonstrate a role for Fas ligand in the autocrine regulation of fibroblast survival. These data suggest that Fas and other cytokines cooperate to regulate renal fibroblast apoptosis. Modulation of the Fas death-signaling pathway in renal fibroblasts could represent a new therapeutic target for renal fibrosis.