tbuckley/cabot-search huggingface dataset:
Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure
Authors: Maarten Naesens, Evelyne Lerut, Marie-Paule Emonds, Albert Herelixka, Pieter Evenepoel, Kathleen Claes, Bert Bammens, Ben Sprangers, Björn Meijers, Ina Jochmans, Diethard Monbaliu, Jacques Pirenne, Dirk R.J. Kuypers
Journal: Journal of the American Society of Nephrology (2015)

Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria <0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3–1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P<0.001), for proteinuria 1.0–3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P<0.001), for proteinuria >3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P<0.001) than at 1, 2, and 5 years after transplant (AUC 0.73, 0.71, and 0.77, respectively, all P<0.001). Independent determinants of proteinuria were repeat transplantation, mean arterial pressure, transplant glomerulopathy, microcirculation inflammation, and de novo/recurrent glomerular disease. The discriminatory power of proteinuria for these intragraft injury processes was better in biopsy samples obtained >3 months after transplant (AUC 0.73, P<0.001) than in those obtained earlier (AUC 0.56, P<0.01), with 85% specificity but lower sensitivity (47.8%) for proteinuria >1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis.
Participation in Cardiac Rehabilitation Programs Among Older Patients After Acute Myocardial Infarction
Authors: Jacob A. Doll, Anne Hellkamp, P. Michael Ho, Michael C. Kontos, Mary A. Whooley, Eric D. Peterson, Tracy Y. Wang
Journal: JAMA Internal Medicine (2015)

This analysis of clinical data linked to Medicare claims finds the cardiac rehabilitation rate for older patients after acute myocardial infarction is low in the United States and suggests efforts be made for increasing referrals, and addressing attendance barriers, to rehabilitation sessions.
Adjuvant CMFVP versus tamoxifen versus concurrent CMFVP and tamoxifen for postmenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.
Authors: S E Rivkin, S Green, B Metch, A B Cruz, M D Abeloff, W R Jewell, J J Costanzi, W B Farrar, J P Minton, C K Osborne
Journal: Journal of Clinical Oncology (1994)

To compare chemohormonal therapy, chemotherapy alone, and hormonal therapy alone in postmenopausal patients with estrogen receptor (ER)-positive operable breast cancer and positive axillary nodes with respect to survival and disease-free survival (DFS).Eight hundred ninety-two postmenopausal women with ER-positive, node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) from July 1979 to March 1989 and 74 by the Eastern Cooperative Oncology Group (ECOG) between June 1987 and March 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive the following: (1) tamoxifen 10 mg twice daily by mouth for 1 year; (2) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (IV) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 IV weekly for 1 year, vincristine .625 mg/m2 IV weekly for the first 10 weeks, and prednisone during weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (3) the combination of tamoxifen and CMFVP.The median follow-up duration is 6.5 years, with a maximum of 12.8 years. Treatment arms are not significantly different with respect to either survival or DFS (log-rank, 2 df, P = .82 and .23, respectively). The 5-year survival rate is 77% for the tamoxifen arm, 78% for CMFVP, and 75% for the combination. No significant differences were observed in node or receptor level subsets. Severe or worse toxicity was experienced by 56% of patients on CMFVP and 61% on CMFVP plus tamoxifen, compared with 5% on tamoxifen alone.CMFVP chemotherapy, either alone or in combination with tamoxifen, has not been shown to be superior to tamoxifen alone in the treatment of postmenopausal women with node-positive, ER-positive, operable breast cancer.
Peritoneal Glucose Exposure and Changes in Membrane Solute Transport with Time on Peritoneal Dialysis
Authors: SIMON J. DAVIES, LOUISE PHILLIPS, PATRICK F. NAISH, GAVIN I. RUSSELL
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Peritoneal solute transport increases with time on treatment in a proportion of peritoneal dialysis (PD) patients, contributing to ultrafiltration failure. Continuous exposure of the peritoneum to hypertonic glucose solutions results in morphologic damage that may have a causative role in changes in peritoneal function. The purpose of this analysis was to establish whether increased exposure to glucose preceded changes in solute transport in a selected group of long-term PD patients. Peritoneal solute transport, residual renal function, peritonitis rate, and peritoneal exposure to glucose were recorded prospectively in a cohort of 303 patients at a single dialysis center. A subgroup of individuals, treated continuously for 5 yr, were identified and defined retrospectively as having either stable or increasing transport status. Of the 22 patients who were treated continuously for 5 yr, 13 had stable solute transport (solute transport at start, 0.67 [±0.1]; at 5 yr, 0.67 [±0.1]), whereas 9 had a sustained increase (solute transport at start, 0.56 [±0.08]; at 5 yr, 0.77 [±0.09]). Compared with the stable patients, those with increasing transport had earlier loss in residual renal function and were exposed to significantly more hypertonic glucose during the first 2 yr of treatment that preceded the increase in solute transport. This was associated with greater achieved ultrafiltration compensating for the reduced urinary volumes in these patients. Further increases in glucose exposure were observed as solute transport continued to rise. Peritonitis, including severity of infection and causative organism, was similar in both groups. In this selected group of long-term survivors on PD, an increase in solute transport with time was preceded by increased peritoneal exposure to hypertonic glucose. This is supportive evidence that hypertonic glucose may play a causative role in alterations in peritoneal membrane function.
Evaluation of renal function in 60 long-term survivors of bone marrow transplantation.
Authors: V Leblond, L Sutton, C Jacquiaud, C Item, R Sadoun, M C Jaudon, F Raymond, C Jacobs, G Deray
Journal: Journal of the American Society of Nephrology (1995)

Although the acute nephrotoxicity of bone marrow transplantation is well documented, long-term follow-up studies are scanty. Renal function was evaluated in 60 long-term survivors of allogeneic (24 patients) or autologous (36 patients) bone marrow transplantation (BMT) with a mean follow-up of 2 yr. Renal function tests included serum creatinine, GFR (inulin clearance), effective RPF (p-aminohyppurate clearance), urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase excretion, and renal tomography. The mean serum creatinine level was 83 +/- 3 and 93 +/- 3 mumol/L before and after grafting, respectively (P < 0.05). The mean GFR (93 +/- 3 mL/min) and effective RPF (419 +/- 16 mL/min) were significantly lower than in healthy controls (120 +/- 3 and 500 +/- 1 mL/min; P < 0.05) and than in candidates for BMT matched for age and hematologic diseases (117 +/- 3 and 469 +/- 11 mL/min; P < 0.05). Thirty-four patients had a fall in the GFR of at least 20%. Patients who received total body irradiation had significant lower creatinine clearance (86 +/- 3 mL/min) and GFR (86 +/- 3 mL/min) than the controls and the patients who received high-dose chemotherapy (100 +/- 4 and 104 +/- 5 mL/min; P < 0.05). These results suggest that subclinical renal dysfunction occurs frequently in marrow graft recipients, especially those who undergo total body irradiation.
Abstract 4279: Rapid biomarker discovery using large-scale, patient-derived cancer genomic cohorts
Authors: Sandeep Sanga, Praveen Nair, Cyrus Mirsaidi, Thomas Broudy
Journal: Cancer Research (2014)

Abstract Target discovery and validation in oncology has largely relied on molecular and functional studies performed in cell lines. Recent advances in genomics have now created large databases based on well-characterized tumor tissue, which has enabled direct investigation of patient tumors for novel targets and predictive markers. Following these discoveries, it is routine to perform functional studies in cell line-based systems; however, it is often challenging to find a relevant cell line model and if found, there are often numerous factors which confound biology when using historical cell lines for functional studies. The result can be a process, which takes considerable time and does not readily translate to clinical relevance. We report here our efforts to identify novel targets and markers through data mining large cohorts of cancer genomics data consisting of samples deriving from both drug-naïve and -treated patient-derived cancer samples. To serve as the drug-naïve reference, we look to the thousands of patient-derived tumor specimens, covering 30+ tissue types, genomically characterized by The Cancer Genome Atlas. For both drug-naïve and drug-treated primary data, we leverage Molecular Response's proprietary bank of viable cryopreserved tumor cells. The bank contains more than 144,000 tumor specimens, covering 25 tissue types and 76 clinical diagnoses. Each of the specimens has been profiled against a panel of drugs ex vivo, and levels of resistance recorded. Nearly 400 tumor specimens from Molecular Response's proprietary bank have been genomically characterized. Station X has designed and developed a software environment called GenePool for the management, analysis and communication of genomic information for cohort-scale biomarker studies. The genomics data along with sample-associated clinical metadata deriving from Molecular Response's bank and The Cancer Genome Atlas were imported into GenePool. We evaluated consistency between drug-naïve samples deriving from the Molecular Response bank and TCGA, and subsequently mined for expression-based markers differentiating varying grades of drug sensitivities from drug-naïve specimens. We are currently evaluating these markers for further functional study in patient-derived models and plan to report to these findings. Citation Format: Sandeep Sanga, Praveen Nair, Cyrus Mirsaidi, Thomas Broudy. Rapid biomarker discovery using large-scale, patient-derived cancer genomic cohorts. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4279. doi:10.1158/1538-7445.AM2014-4279
Preschool vision screening: summary of a task force report11Previously published in Pediatrics, 106:1105–1116, 2000. Reprinted with permission.
Authors: E.Eugenie Hartmann, Velma Dobson, Louise Hainline, Wendy Marsh-Tootle, Graham E Quinn, Mark S Ruttum, Paulette P Schmidt, Kurt Simons
Journal: Ophthalmology (2001)
Ovarian and extragonadal malignant germ-cell tumors in females: A single-institution experience with 43 patients
Authors: J.I. Mayordomo, L. Paz-Ares, F. Rivera, M. López-Brea, E. López Martín, C. Mendiola, M.T. Díaz-Puente, P. Lianes, H. Cortés-Funes, M.D. García-Prats
Journal: Annals of Oncology (1994)
Atopy is a risk factor for adult asthma in urban community of South Western Nigeria
Authors: Olusoji Ige, Adegoke Falade, Ganiyu Arinola
Journal: European Respiratory Journal (2013)

Objective: To determine the interaction between factors such as atopy, environmental exposure, and urbanization and helminthic infections in modulating asthma among adult asthmatics in Urban setting in Nigeria  Methods: A random sample of 22 (10M, 12F) consecutive asthmatics, seen in the outpatient pulmonary clinic of University College Hospital Ibadan and 27(13M,14F) age and gender matched controls underwent evaluation which included blood tests for eosinophils, serum IgE, allergy skin tests to 8 common environmental allergens and spirometry. The modified version of the questionnaire of the International study of Asthma and Allergies in Children (ISAAC) Phase III used by the same study group of researcher in Nigeria was used to assess the asthma symptoms. Wilcoxen sign-rank tests were used to compare eosinophil counts, percentage eosinophil and allergic skin test between the two groups, while paired t test was used to compare spirometry variables  Results: Asthmatics had significantly more positive skin reaction to house dust mite, mould, than controls (P  Total serum IgE was also significantly higher in asthmatics than in controls (mean 210 vs.60 IU/ml; P=0.003).However no significant differences were observed in total eaosinophil counts. No significant difference in the degree of intestinal helminth infection in the two groups. Which means stool parasitism was similar. FEV1% was significantly lower in asthmatics (p=0.02) but FEV1 was similar between the 2 groups (P=0.02)  Conclusion: The elevated levels of IgE and positive skin reactions to some of the common environmental allergens suggest an important role of atopy in the expression of asthma in this developing country’s urban setting.
Semen analysis and cryoconservation before treatment in Hodgkin's disease
Authors: O. Fitoussi, H. Eghbali, N. Tchen, J.P. Berjon, P. Soubeyran, B. Hcerni
Journal: Annals of Oncology (2000)

The prophylaxis of the late effects of chemotherapy and radiotherapy has become one of the major concerns in the management of Hodgkin's disease (HD). Unlike other complications, male sterility could be managed by prior semen preservation (SP).To evaluate the semen quality of patients with HD and the outcome of insemination, we reviewed spermograms of patients who underwent SP before any treatment. The following criteria were necessary: 1) age > 16 and < 50; 2) HD of any stage; 3) informed about male sterility after HD treatment; 4) fully consenting.Such a proposal was made to 316 men, and 94 fulfilled the criteria. All patients underwent an initial chemotherapy. Mean age of the cohort was 27.5 years (range 16-48 years). Pretherapeutic staging of HD revealed 38 stage I (40%), 38 II (38%), 14 III (15%) and 4 IV (4%). Semen analysis before cryoconservation showed an overall 53% of normal or subnormal cases (50 cases). The analysis of semen quality and spermatozoid amount according to various parameters failed to find a correlation with stage, B symptoms, age, or biologic data (LDH, WBC, platelets, ESR). The use of cryopreserved semen was requested by 13 patients; 88 inseminations were performed leading to 9 pregnancies and 2 births.The low rate of success with cryopreserved semen in these cases suggests the need for a more careful design of non-toxic chemotherapy regimens in combined modality treatment.
Body composition analysis on COPD patients – Results of prospective study
Authors: Jan Plutinsky, Ivan Marget, Petra Kubicova, Peter Chlebo, Dalibor Petras, Daniel Magula
Journal: European Respiratory Journal (2011)

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is in close relation to chronic systemic inflammation involving an extrapulmonary patholgy. The results can be weight and muscle loss and nutritional abnormalities. FFMI (Fat Free Mass-index) assessment is important, because using Body Mass Index (BMI) does not distinguish between two people with a similar BMI but different body composition (BC).

Aims: To determine FFMI and BMI in COPD patients (pts).

Methods: In 2010, we began BC analysis on COPD patients with Dual-Energy X-ray Absorbtiometry (DEXA) in a prospective study trial. We analysed BC of 30 clinically stable COPD pts in stage II-IV GOLD. There were 24 M, median age 69 yrs (49-84 yrs) and 6 F, median age 74 yrs (51-85 yrs). For body composition analysis by DEXA we used Hologic Discovery Wi including the software “Whole Body Composition Analysis”. Reference intervals (by Schutz) for FFMI were used.

Results: In M median BMI was 23 (17.7-33.99) and 23.34 (14.79-37.49) in F respectively. FFMI was 17.78 (14.52-22.18) and 15.47 (12.41-20.36) respectively. 13/30 pts had FFMI under the 10th percentile for their gender and age category. 16/30 pts had FFMI under the 25th percentile. The highest prevalence of low FFMI was seen in GOLD stage IV.

Conclusions: In our group, most of pts had FFMI <25th percentile. Those pts with FFMI<10th percentile have a higher risk for future physical disability. In our opinion, pts with FFMI <25th percentile need help to change their dietary habits, physical rehabilitation and nutrition support to prevent the progression of disease. Determination of FFMI would help to create procedrulas formulas for COPD pts with muscle weakness and/or terminal cachexia.
Activation of sphingosine kinase 2 by endoplasmic reticulum stress ameliorates hepatic steatosis and insulin resistance in mice
Authors: Su‐Yeon Lee, In‐Kyung Hong, Bo‐Rahm Kim, Soon‐Mi Shim, Jae Sung Lee, Hui‐Young Lee, Cheol Soo Choi, Bo‐Kyung Kim, Tae‐Sik Park
Journal: Hepatology (2015)

The endoplasmic reticulum (ER) is the principal organelle in the cell for protein folding and trafficking, lipid synthesis, and cellular calcium homeostasis. Perturbation of ER function results in activation of the unfolded protein response (UPR) and is implicated in abnormal lipid biosynthesis and development of insulin resistance. In this study, we investigated whether transcription of sphingosine kinase (Sphk)2 is regulated by ER stress-mediated UPR pathways. Sphk2, a major isotype of sphingosine kinase in the liver, was transcriptionally up-regulated by tunicamycin and lipopolysaccharides. Transcriptional regulation of Sphk2 was mediated by activation of activating transcription factor (ATF)4 as demonstrated by promoter assays, immunoblotting, and small interfering RNA analyses. In primary hepatocytes, adenoviral Sphk2 expression elevated cellular sphingosine 1 phosphate (S1P) and activated protein kinase B phosphorylation, with no alteration of insulin receptor substrate phosphorylation. Hepatic overexpression of Sphk2 in mice fed a high-fat diet (HFD) led to elevated S1P and reduced ceramide, sphingomyelin, and glucosylceramide in plasma and liver. Hepatic accumulation of lipid droplets by HFD feeding was reduced by Sphk2-mediated up-regulation of fatty acid (FA) oxidizing genes and increased FA oxidation in liver. In addition, glucose intolerance and insulin resistance were ameliorated by improved hepatic insulin signaling through Sphk2 up-regulation.Sphk2 is transcriptionally up-regulated by acute ER stress through activation of ATF4 and improves perturbed hepatic glucose and FA metabolism.
Chemokine and their receptors mRNA expression in brush-biopsies of nasopharynx in bronchial asthma patients
Authors: Kirill Sysoev, Anna Bibkova, Vasily Trofimov, Areg Totolian
Journal: European Respiratory Journal (2011)

Introduction:  Mechanism of BA onset and progression at different ages are still poorly understood. System of chemokines in upper airways is a tempting object of investigation BA pathogenesis.   Methods:  We examined 70 patients with asthma. The patients age ranged from 16 to 74 years. Were studied 31 men and 39 women. The control group used brush-biopsy 17 healthy volunteers with no history of atopic diseases. Were studied mRNA of eotaxin, eotaxin-2, MIP-1α, MIP-1β, RANTES, CCR1, CCR3, CCR5, CXCR1, and CXCR2.   Results:  A study in patients with asthma was revealed a significant increase in eotaxin mRNA expression (p = 0.045), eotaxin-2 (0.036), MIP-1α (0.0003), MIP-1β (0.002) and CXCR1 (0.004) compared with healthy volunteers. At the same time CCR1 gene expression in patients with asthma was reduced compared with control. To study the age dynamics of the asthma patients were divided into 4 groups: first group - 16-25 years (n = 14), the second group - 26-39 years (n = 14), the third group - 40-53 years (n = 21) and the fourth group - 54-74 years (n = 21). Eotaxin-2 had wave-like dynamics depending on patents age. MIP-1α was lowest in the second and third groups, and in the first and fourth - were significantly higher. The values of MIP-1β - the lowest in the first group with increasing age became more and peaked in the fourth group. mRNA of CCR1 and CXCR1 was significantly decreased in the second group compared to the first, meanwhile in the third and fourth ones levels of mRNA of both receptors increases depending on the age of the patients.   Conclusion:  The state of chemokines and relative receptors gene expression in upper airways reflects age features of BA pathogenesis.
Mevalonate Pathway Antagonist Suppresses Formation of Serous Tubal Intraepithelial Carcinoma and Ovarian Carcinoma in Mouse Models
Authors: Yusuke Kobayashi, Hiroyasu Kashima, Ren-Chin Wu, Jin-Gyoung Jung, Jen-Chun Kuan, Jinghua Gu, Jianhua Xuan, Lori Sokoll, Kala Visvanathan, Ie-Ming Shih, Tian-Li Wang
Journal: Clinical Cancer Research (2015)

Statins are among the most frequently prescribed drugs because of their efficacy and low toxicity in treating hypercholesterolemia. Recently, statins have been reported to inhibit the proliferative activity of cancer cells, especially those with TP53 mutations. Because TP53 mutations occur in almost all ovarian high-grade serous carcinoma (HGSC), we determined whether statins suppressed tumor growth in animal models of ovarian cancer.Two ovarian cancer mouse models were used. The first one was a genetically engineered model, mogp-TAg, in which the promoter of oviduct glycoprotein-1 was used to drive the expression of SV40 T-antigen in gynecologic tissues. These mice spontaneously developed serous tubal intraepithelial carcinomas (STICs), which are known as ovarian cancer precursor lesions. The second model was a xenograft tumor model in which human ovarian cancer cells were inoculated into immunocompromised mice. Mice in both models were treated with lovastatin, and effects on tumor growth were monitored. The molecular mechanisms underlying the antitumor effects of lovastatin were also investigated.Lovastatin significantly reduced the development of STICs in mogp-TAg mice and inhibited ovarian tumor growth in the mouse xenograft model. Knockdown of prenylation enzymes in the mevalonate pathway recapitulated the lovastatin-induced antiproliferative phenotype. Transcriptome analysis indicated that lovastatin affected the expression of genes associated with DNA replication, Rho/PLC signaling, glycolysis, and cholesterol biosynthesis pathways, suggesting that statins have pleiotropic effects on tumor cells.The above results suggest that repurposing statin drugs for ovarian cancer may provide a promising strategy to prevent and manage this devastating disease.