Recent Stanford Publications in PubMed
- Flow-through omental flap to free anterolateral thigh flap for complex chest wall reconstruction: Case report and review of the literature.Luan A, Galvez MG, Lee GKMicrosurgery
- Reverse retrospective motion correction.Zahneisen B, Keating B, Singh A, Herbst M, Ernst TMagn Reson Med
- Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents.Botkin JR, Belmont JW, Berg JS, Berkman BE, Bombard Y, Holm IA, Levy HP, Ormond KE, Saal HM, Spinner NB, Wilfond BS, McInerney JDAm J Hum Genet
- Quantifying the influence of measured and unmeasured individual differences on demography.Plard F, Gaillard JM, Coulson T, Delorme D, Warnant C, Michallet J, Tuljapurkar S, Krishnakumar S, Bonenfant CJ Anim Ecol
- Clinical Evidence Summary Apps: Definition, Role, and Unknowns About a Novel Medical Content Delivery Genre.Plante TB, Kane SP, Iberri DJ, Majure DTJ Grad Med Educ
- Too late to back out? Options for breech presentation management.Sharoni L, Lyell DJ, Weiniger CFJ Epidemiol Community Health
- Transplant immuno-diagnostics: crossmatch and antigen detection.South AM, Grimm PCPediatr Nephrol
- Fracture Burden and Risk Factors in Childhood CKD: Results from the CKiD Cohort Study.Denburg MR, Kumar J, Jemielita T, Brooks ER, Skversky A, Portale AA, Salusky IB, Warady BA, Furth SL, Leonard MBJ Am Soc Nephrol
- Charge-order domain walls with enhanced conductivity in a layered manganite.Ma EY, Bryant B, Tokunaga Y, Aeppli G, Tokura Y, Shen ZXNat Commun
- Variation in Use of Pediatric Cardiology Subspecialty Care: A Total Population Study in California, 1983 to 2011.Chamberlain LJ, Fernandes SM, Saynina O, Grady S, Sanders L, Staves K, Wise PHJ Am Coll Cardiol
- Surgical Repair of Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collaterals With Absent Intrapericardial Pulmonary Arteries.Carrillo SA, Mainwaring RD, Patrick WL, Bauser-Heaton HD, Peng L, Reddy VM, Hanley FLAnn Thorac Surg
- The Relationship Between Industry and Pain Societies, Part 1: Demystification and Legitimization of Continuing Medical Education.Darnall BD, Schatman MEPain Med
- Economic Burden of Undiagnosed Nonvalvular Atrial Fibrillation in the United States.Turakhia MP, Shafrin J, Bognar K, Goldman DP, Mendys PM, Abdulsattar Y, Wiederkehr D, Trocio JAm J Cardiol
- Genetic determinants of telomere length and risk of common cancers: a Mendelian randomization study.Zhang C, Doherty JA, Burgess S, Hung RJ, Lindström S, Kraft P, Gong J, Amos C, Sellers TA, Monteiro AN, Chenevix-Trench G, Bickeböller H, Risch A, Brennan P, McKay J, Houlston R, Landi MT, Timofeeva M, Wang Y, Heinrich J, Kote-Jarai Z, Eeles RA, Muir K, Wiklund F, Grönberg H, Berndt SI, Chanock SJ, Schumacher F, Haiman CA, Henderson BE, Amin Al Olama A, Andrulis IL, Hopper JL, Chang-Claude J, John EM, Malone KE, Gammon MD, Ursin G, Whittemore AS, Hunter DJ, Gruber SB, Knight JA, Hou L, Le Marchand L, Newcomb PA, Hudson TJ, Chan AT, Li L, Woods MO, Ahsan H, Pierce BL, GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICLHum Mol Genet
- Genome-wide association studies for taxane-induced peripheral neuropathy (TIPN) in ECOG-5103 and ECOG-1199.Schneider BP, Li L, Radovich M, Shen F, Miller C, Flockhart DA, Jiang G, Vance GH, Gardner L, Vatta M, Bai C, Lai D, Koller D, Zhao F, O'Neill A, Smith ML, Railey E, White C, Patridge A, Sparano JA, Davidson NE, Foroud T, Sledge GWClin Cancer Res
- Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry.Benham-Pyle BW, Pruitt BL, Nelson WJScience
- Microbial diversity. Fine-scale diversity and extensive recombination in a quasisexual bacterial population occupying a broad niche.Rosen MJ, Davison M, Bhaya D, Fisher DSScience
- Methylation gets into rhythm with NAD(+)-SIRT1.Tasselli L, Chua KFNat Struct Mol Biol
- Poor Sustained Virological Response in a Multicenter Real-Life Cohort of Chronic Hepatitis C Patients Treated with Pegylated Interferon and Ribavirin plus Telaprevir or Boceprevir.Vo KP, Vutien P, Akiyama MJ, Vu VD, Ha NB, Piotrowski JI, Wantuck J, Roytman MM, Tsai N, Cheung R, Li J, Nguyen MHDig Dis Sci
- Loss of HIF-1α in the notochord results in cell death and complete disappearance of the nucleus pulposus.Merceron C, Mangiavini L, Robling A, Wilson TL, Giaccia AJ, Shapiro IM, Schipani E, Risbud MVPLoS One
- Text mining for adverse drug events: the promise, challenges, and state of the art.Harpaz R, Callahan A, Tamang S, Low Y, Odgers D, Finlayson S, Jung K, LePendu P, Shah NHDrug Saf
- Coping and glucocorticoid receptor regulation by stress inoculation.Lee AG, Buckmaster CL, Yi E, Schatzberg AF, Lyons DMPsychoneuroendocrinology
- Gastric outlet obstruction caused by heterotopic pancreas in an adolescent.Rodriguez AA, Berquist W, Bingham DDig Dis Sci
Flow-through omental flap to free anterolateral thigh flap for complex chest wall reconstruction: Case report and review of the literature.
Microsurgery. 2015 Jul 3;
Authors: Luan A, Galvez MG, Lee GK
Despite the options currently available for chest wall reconstruction, patients with complex composite defects may still pose a significant challenge for the reconstructive surgeon when only using conventional methods. In particular, prior radiotherapy and/or large en bloc resection may leave inadequate regional flaps and recipient vessels for free tissue transfer. Here, we describe a case in which we reconstruct a 14 cm × 18 cm complex chest wall defect, secondary to tumor resection and infected sternum debridement, with a pedicled flow-through omental flap to a 14 cm × 22 cm free anterolateral thigh flap using the omental gastroepiploic vessels as recipient vessels. Reconstruction was successful with excellent flap viability, and no complications at recipient or donor sites. We review the literature on complex chest wall reconstruction and introduce this valuable option of utilizing a pedicled omental flap as a flow-through flap to a free flap for patients without viable recipient vessels or local flaps. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015.
PMID: 26140609 [PubMed - as supplied by publisher]
Reverse retrospective motion correction.
Magn Reson Med. 2015 Jul 3;
Authors: Zahneisen B, Keating B, Singh A, Herbst M, Ernst T
PURPOSE: One potential barrier for using prospective motion correction (PMC) in the clinic is the unpredictable nature of a scan because of the direct interference with the imaging sequence. We demonstrate that a second set of "de-corrected" images can be reconstructed from a scan with PMC that show how images would have appeared without PMC enabled.
THEORY AND METHODS: For three-dimensional scans, the effects of PMC can be undone by performing a retrospective reconstruction based on the inverse of the transformation matrix used for real time gradient feedback. Retrospective reconstruction is performed using a generalized SENSE approach with continuous head motion monitored using a single-marker optical camera system.
RESULTS: Reverse retrospective reconstruction is demonstrated for phantom and in vivo scans using an magnetization-prepared rapid gradient echo (MPRAGE) sequence including parallel and Partial Fourier acceleration.
CONCLUSION: Reverse retrospective reconstruction can almost perfectly undo the effects of prospective feedback, and thereby provide a second image data set with the effects of motion correction removed. In case of correct feedback, one can directly compare the quality of the corrected with that of the uncorrected scan. Additionally, because erroneous feedback during PMC may introduce artifacts, it is possible to eliminate artifacts in a corrupted scan by reversing the false gradient updates. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.
PMID: 26140504 [PubMed - as supplied by publisher]
Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents.
Am J Hum Genet. 2015 Jul 2;97(1):6-21
Authors: Botkin JR, Belmont JW, Berg JS, Berkman BE, Bombard Y, Holm IA, Levy HP, Ormond KE, Saal HM, Spinner NB, Wilfond BS, McInerney JD
In 1995, the American Society of Human Genetics (ASHG) and American College of Medical Genetics and Genomics (ACMG) jointly published a statement on genetic testing in children and adolescents. In the past 20 years, much has changed in the field of genetics, including the development of powerful new technologies, new data from genetic research on children and adolescents, and substantial clinical experience. This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children. These recommendations are relevant to families, clinicians, and investigators. After a brief review of the 1995 statement and major changes in genetic technologies in recent years, this statement offers points to consider on a broad range of test technologies and their applications in clinical medicine and research. Recommendations are also made for record and communication issues in this domain and for professional education.
PMID: 26140447 [PubMed - as supplied by publisher]
Quantifying the influence of measured and unmeasured individual differences on demography.
J Anim Ecol. 2015 Jul 3;
Authors: Plard F, Gaillard JM, Coulson T, Delorme D, Warnant C, Michallet J, Tuljapurkar S, Krishnakumar S, Bonenfant C
Demographic rates can vary not only with measured individual characters like age, sex and mass but also with unmeasured individual variables like behaviour, genes and health. Predictions from population models that include measured individual characteristics often differ from models that exclude them. Similarly, unmeasured individual differences have the potential to impact predictions from population models. However, unmeasured individual differences are rarely included in population models. We construct stage- and age-structured models (where stage is mass) of a roe deer population, which are parameterized from statistical functions that either include, or ignore, unmeasured individual differences. We found that mass and age structures substantially impacted model parameters describing population dynamics, as did temporal environmental variation, while unmeasured individual differences impacted parameters describing population dynamics to a much smaller extent once individual heterogeneity related to mass and age has been included in the model. We discuss how our assumptions (unmeasured individual differences only in mean trait values) could have influenced our findings and under what circumstances unmeasured individual differences could have had a larger impact on population dynamics. There are two reasons explaining the relative small influence of unmeasured individual differences on population dynamics in roe deer. First, individual body mass and age both capture a large amount of individual differences in roe deer. Second, in large populations of long-lived animals, the average quality of individuals (independent of age and mass) within the population is unlikely to show substantial variation over time, unless rapid evolution is occurring. So even though a population consisting of high-quality individuals would have much higher population growth rate than a population consisting of low-quality individuals, the probability of observing a population consisting only of high-quality individuals is small.
PMID: 26140296 [PubMed - as supplied by publisher]
Clinical Evidence Summary Apps: Definition, Role, and Unknowns About a Novel Medical Content Delivery Genre.
J Grad Med Educ. 2014 Dec;6(4):791
Authors: Plante TB, Kane SP, Iberri DJ, Majure DT
PMID: 26140138 [PubMed]
Too late to back out? Options for breech presentation management.
J Epidemiol Community Health. 2015 Jul 2;
Authors: Sharoni L, Lyell DJ, Weiniger CF
PMID: 26139643 [PubMed - as supplied by publisher]
Transplant immuno-diagnostics: crossmatch and antigen detection.
Pediatr Nephrol. 2015 Jul 3;
Authors: South AM, Grimm PC
Identifying and monitoring donor-directed anti-human leukocyte antigen antibodies are a rapidly evolving area of solid organ transplantation. Donor-specific antibodies dictate pre-transplant donor choice and donor-recipient matching and underlie much acute and chronic allograft rejection and loss. The evolution of available technology has driven this progress. Early, labor-intensive, whole-cell assays based on complement-dependent cytotoxicity suffered from poor sensitivity and specificity, technical challenges and lack of precision. Sequential improvement in assay performance included anti-human immunoglobulin-enhanced, complement-dependent cytotoxicity techniques followed by cell-based flow cytometry. However, variable specificity and sensitivity inherent in cell-based testing continued to limit flow cytometry. The introduction of solid-phase assays led to a second revolution in histocompatibility testing with the use of purified antigens bound to artificial surfaces rather than whole cells. These techniques augmented sensitivity and specificity to detect even low-titer antibodies to previously undetected antigens. Identification of complement-activating antibodies is being introduced, but current technology is in the developmental stage. While the detection of alloantibodies has improved dramatically, our comprehension of their importance remains imperfect. Variability in methodology and a lack of standardization limits the clinical application of these tests. In spite of the hurdles that remain, antibody-mediated rejection has become a key target to improve graft survival.
PMID: 26139577 [PubMed - as supplied by publisher]
Fracture Burden and Risk Factors in Childhood CKD: Results from the CKiD Cohort Study.
J Am Soc Nephrol. 2015 Jul 2;
Authors: Denburg MR, Kumar J, Jemielita T, Brooks ER, Skversky A, Portale AA, Salusky IB, Warady BA, Furth SL, Leonard MB
Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence interval [95% CI], 293-533) and 323 (95% CI, 216-481) fractures per 10,000 person-years, respectively. These rates were 2- to 3-fold higher than published general population rates. The only gender difference in fracture risk was a 2.6-fold higher risk in males aged ≥15 years (570/10,000 person-years, adjusted P=0.04). In multivariable analysis, advanced pubertal stage, greater height Z-score, difficulty walking, and higher average log-transformed parathyroid hormone level were independently associated with greater fracture risk (all P≤0.04). Phosphate binder treatment (predominantly calcium-based) was associated with lower fracture risk (hazard ratio, 0.37; 95% CI, 0.15-0.91; P=0.03). Participation in more than one team sport was associated with higher risk (hazard ratio, 4.87; 95% CI, 2.21-10.75; P<0.001). In conclusion, children with CKD have a high burden of fracture. Regarding modifiable factors, higher average parathyroid hormone level was associated with greater risk of fracture, whereas phosphate binder use was protective in this cohort.
PMID: 26139439 [PubMed - as supplied by publisher]
Charge-order domain walls with enhanced conductivity in a layered manganite.
Nat Commun. 2015;6:7595
Authors: Ma EY, Bryant B, Tokunaga Y, Aeppli G, Tokura Y, Shen ZX
Interfaces and boundaries in condensed-matter systems often have electronic properties distinct from the bulk material and thus have become a topic of both fundamental scientific interest and technological importance. Here we identify, using microwave impedance microscopy, enhanced conductivity of charge-order domain walls in the layered manganite Pr(Sr0.1Ca0.9)2Mn2O7. We obtain a complete mesoscopic map of surface topography, crystalline orientation and electronic phase, and visualize the thermal phase transition between two charge-ordered phases. In both phases, charge-order domains occur with domain walls showing enhanced conductivity likely due to local lifting of the charge order. Finite element analysis shows that the resolved domain walls can be as narrow as few nanometres. The domain walls are stabilized by structural twins and have a strong history dependence, suggesting that they may be manipulated to create novel devices.
PMID: 26139185 [PubMed - as supplied by publisher]
Variation in Use of Pediatric Cardiology Subspecialty Care: A Total Population Study in California, 1983 to 2011.
J Am Coll Cardiol. 2015 Jul 7;66(1):37-44
Authors: Chamberlain LJ, Fernandes SM, Saynina O, Grady S, Sanders L, Staves K, Wise PH
BACKGROUND: American Academy of Pediatrics guidelines emphasize regionalized systems of care for pediatric chronic illness. There remains a paucity of information on the status of regionalized systems of care for pediatric congenital heart disease (CHD).
OBJECTIVES: This study evaluated variations in use of pediatric cardiology specialty care centers (PCSCC) for pediatric patients with CHD in California between 1983 and 2011.
METHODS: We performed a retrospective, total population analysis of pediatric CHD patients using the California Office of Statewide Health Planning and Development unmasked database. PCSCCs were identified by California's Title V program.
RESULTS: There were 164,310 discharges meeting inclusion criterion. Discharges from PCSCCs grew from 58% to 88% between 1983 and 2011. Regionalized care was highest for surgical (96%) versus nonsurgical (71%) admissions. Admissions with a public payer increased from 42% (1983) to 61% (2011). Total bed days nearly doubled, and median length of stay increased from 2 to 3 days (nonspecialty care) and from 4 to 5 days (specialty care). There was a decrease in the pediatric CHD in-hospital death rate from 5.1 to 2.3 per 100,000 between 1983 and 2011, and a shift toward a larger percent of deaths occurring in the newborn period.
CONCLUSIONS: California's inpatient regionalized specialty care of pediatric CHD has increased substantially since 1983, especially for surgical CHD discharges. The death rate has decreased, the number of bed days has increased, and a large proportion of these discharges now have public payers. Health care reform efforts must consider these shifts while protecting advances in regionalization of pediatric CHD care.
PMID: 26139056 [PubMed - in process]
Surgical Repair of Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collaterals With Absent Intrapericardial Pulmonary Arteries.
Ann Thorac Surg. 2015 Jun 30;
Authors: Carrillo SA, Mainwaring RD, Patrick WL, Bauser-Heaton HD, Peng L, Reddy VM, Hanley FL
BACKGROUND: One anatomic variant of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals (PA/VSD/MAPCAs) is characterized by the absence of intrapericardial pulmonary arteries. This anatomy obviates the possibility of incorporating the pulmonary arteries for reconstruction or palliative procedures. The purpose of this study was to evaluate the surgical results in patients undergoing repair of PA/VSD/MAPCAs with absent pulmonary arteries.
METHODS: This was a retrospective review of 35 patients who underwent surgical repair of PA/VSD/MAPCAs with absent pulmonary arteries between 2007 and 2014. The median age at the time of surgery was 3.4 months, and the median weight was 4.9 kg. All patients underwent unifocalization of MAPCAs, with an average of 3.5 ± 1.4 MAPCAs per patient.
RESULTS: Twenty-eight of the 35 patients (80%) underwent complete single-stage surgical repair, including unifocalization of MAPCAs, VSD closure, and right ventricle to pulmonary artery conduit. After complete repair, the average right ventricular to aortic pressure ratio was 0.33 ± 0.07. There were no deaths in this subgroup. Seven patients (20%) were not deemed suitable candidates for VSD closure after their unifocalization procedure, and therefore underwent palliation with a central shunt. There was 1 operative death and 1 interim death. Three patients have subsequently undergone complete repair, and 2 are awaiting further evaluation and treatment.
CONCLUSIONS: The majority of patients with PA/VSD/MAPCAs and absent pulmonary arteries can undergo complete single-stage repair with satisfactory postoperative hemodynamics. These results suggest that unifocalization of MAPCAs can provide a reasonable pulmonary vascular bed in the absence of intrapericardial pulmonary arteries.
PMID: 26138766 [PubMed - as supplied by publisher]
The Relationship Between Industry and Pain Societies, Part 1: Demystification and Legitimization of Continuing Medical Education.
Pain Med. 2015 Jul 1;
Authors: Darnall BD, Schatman ME
PMID: 26138746 [PubMed - as supplied by publisher]
Economic Burden of Undiagnosed Nonvalvular Atrial Fibrillation in the United States.
Am J Cardiol. 2015 Jun 4;
Authors: Turakhia MP, Shafrin J, Bognar K, Goldman DP, Mendys PM, Abdulsattar Y, Wiederkehr D, Trocio J
Atrial fibrillation (AF) may be clinically silent and therefore undiagnosed. To date, no estimates of the direct medical cost of undiagnosed AF exist. We estimated the United States (US) incremental cost burden of undiagnosed nonvalvular AF nationally using administrative claims data. To calculate the incremental costs of undiagnosed AF, we compared annual medical costs (in 2014 US Dollars) for patients with AF compared to propensity-matched controls and multiplied this by estimates of undiagnosed AF prevalence derived from the same data sources. The study population included US residents aged ≥18 years with 24 months of continuous enrollment drawn from 2 large administrative claims databases. Mean per capita medical spending for patients with AF aged from 18 to 64 year was $38,861 (95% confidence interval [CI] $35,781 to $41,950) compared to $28,506 (95% CI $28,409 to $28,603) for similar patients without AF (incremental cost difference $10,355, p <0.001); total spending for patients aged ≥65 years with AF was $25,322 (95% CI $25,049 to $25,595) compared to $21,706 (95% CI $21,563 to $21,849) for similar patients without AF (incremental cost difference $3,616, p <0.001). Using estimates of the US prevalence of undiagnosed AF (596,000) drawn from the same data, we estimated that the US incremental cost burden of undiagnosed nonvalvular AF is $3.1 billion (95% CI $2.7 to $3.7 billion). In conclusion, the direct medical costs for patients with undiagnosed AF are greater than patients with similar observable characteristics without AF and strategies to identify and treat patients with undiagnosed AF could lead to sizable reductions in stroke sequelae and associated costs.
PMID: 26138378 [PubMed - as supplied by publisher]
Genetic determinants of telomere length and risk of common cancers: a Mendelian randomization study.
Hum Mol Genet. 2015 Jul 2;
Authors: Zhang C, Doherty JA, Burgess S, Hung RJ, Lindström S, Kraft P, Gong J, Amos C, Sellers TA, Monteiro AN, Chenevix-Trench G, Bickeböller H, Risch A, Brennan P, McKay J, Houlston R, Landi MT, Timofeeva M, Wang Y, Heinrich J, Kote-Jarai Z, Eeles RA, Muir K, Wiklund F, Grönberg H, Berndt SI, Chanock SJ, Schumacher F, Haiman CA, Henderson BE, Amin Al Olama A, Andrulis IL, Hopper JL, Chang-Claude J, John EM, Malone KE, Gammon MD, Ursin G, Whittemore AS, Hunter DJ, Gruber SB, Knight JA, Hou L, Le Marchand L, Newcomb PA, Hudson TJ, Chan AT, Li L, Woods MO, Ahsan H, Pierce BL, GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL
Epidemiological studies have reported inconsistent associations between telomere length (TL) and risk for various cancers. These inconsistencies are likely attributable, in part, to biases that arise due to post-diagnostic and post-treatment TL measurement. To avoid such biases, we used a Mendelian randomization approach and estimated associations between nine TL-associated SNPs and risk for five common cancer types (breast, lung, colorectal, ovarian and prostate cancer, including subtypes) using data on 51,725 cases and 62,035 controls. We then used an inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long TL and cancer risk. The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma (P=6.3x10(-15)), even after exclusion of a SNP residing in a known lung cancer susceptibility region (TERT-CLPTM1L) P=6.6x10(-6)). Under Mendelian randomization assumptions, the association estimate (odds ratio (OR)=2.78) is interpreted as the OR for lung adenocarcinoma corresponding to a 1000 base pair increase in TL. The weighted TL SNP score was not associated with other cancer types or subtypes. Our finding that genetic determinants of long TL increase lung adenocarcinoma risk avoids issues with reverse causality and residual confounding that arise in observational studies of TL and disease risk. Under Mendelian randomization assumptions, our finding suggests that longer TL increases lung adenocarcinoma risk. However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in lung adenocarcinoma risk.
PMID: 26138067 [PubMed - as supplied by publisher]
Genome-wide association studies for taxane-induced peripheral neuropathy (TIPN) in ECOG-5103 and ECOG-1199.
Clin Cancer Res. 2015 Jul 2;
Authors: Schneider BP, Li L, Radovich M, Shen F, Miller C, Flockhart DA, Jiang G, Vance GH, Gardner L, Vatta M, Bai C, Lai D, Koller D, Zhao F, O'Neill A, Smith ML, Railey E, White C, Patridge A, Sparano JA, Davidson NE, Foroud T, Sledge GW
Purpose Taxane induced peripheral neuropathy (TIPN) is an important survivorship issue for many cancer patients. Currently, there are no clinically implemented biomarkers to predict which patients might be at increased risk for TIPN. We present a comprehensive approach to identification of genetic variants to predict TIPN. Experimental Design We performed a genome wide association study (GWAS) in 3431 patients from the phase III adjuvant breast cancer trial, ECOG-5103 to compare genotypes with TIPN. We performed candidate validation of top SNPs for TIPN in another phase III adjuvant breast cancer trial, ECOG-1199. Results When evaluating for Grade 3-4 TIPN, 120 SNPs had a p-value <10-4 from patients of European descent (EA) in ECOG-5103. 30 candidate SNPs were subsequently tested in ECOG-1199 and SNP rs3125923 was found to be significantly associated with Grade 3-4 TIPN (p=1.7x10-3; OR=1.8). Race was also a major predictor of TIPN, with patients of African descent (AA) experiencing increased risk of Grade 2-4 TIPN (HR=2.1; p=5.6×10-16) and Grade 3-4 TIPN (HR=2.6; p=1.1×10-11) compared with others. A SNP in FCAMR, rs1856746, had a trend toward an association with Grade 2-4 TIPN in AA patients from the GWAS in ECOG-5103 (OR=5.5; p=1.6x10-7). Conclusion rs3125923 represents a validated SNP to predict Grade 3-4 TIPN. Genetically determined AA race represents the most significant predictor of TIPN.
PMID: 26138065 [PubMed - as supplied by publisher]
Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry.
Science. 2015 May 29;348(6238):1024-7
Authors: Benham-Pyle BW, Pruitt BL, Nelson WJ
Mechanical strain regulates the development, organization, and function of multicellular tissues, but mechanisms linking mechanical strain and cell-cell junction proteins to cellular responses are poorly understood. Here, we showed that mechanical strain applied to quiescent epithelial cells induced rapid cell cycle reentry, mediated by independent nuclear accumulation and transcriptional activity of first Yap1 and then β-catenin. Inhibition of Yap1- and β-catenin-mediated transcription blocked cell cycle reentry and progression through G1 into S phase, respectively. Maintenance of quiescence, Yap1 nuclear exclusion, and β-catenin transcriptional responses to mechanical strain required E-cadherin extracellular engagement. Thus, activation of Yap1 and β-catenin may represent a master regulator of mechanical strain-induced cell proliferation, and cadherins provide signaling centers required for cellular responses to externally applied force.
PMID: 26023140 [PubMed - indexed for MEDLINE]
Microbial diversity. Fine-scale diversity and extensive recombination in a quasisexual bacterial population occupying a broad niche.
Science. 2015 May 29;348(6238):1019-23
Authors: Rosen MJ, Davison M, Bhaya D, Fisher DS
Extensive fine-scale genetic diversity is found in many microbial species across varied environments, but for most, the evolutionary scenarios that generate the observed variation remain unclear. Deep sequencing of a thermophilic cyanobacterial population and analysis of the statistics of synonymous single-nucleotide polymorphisms revealed a high rate of homologous recombination and departures from neutral drift consistent with the effects of genetic hitchhiking. A sequenced isolate genome resembled an unlinked random mixture of the allelic diversity at the sampled loci. These observations suggested a quasisexual microbial population that occupies a broad ecological niche, with selection driving frequencies of alleles rather than whole genomes.
PMID: 26023139 [PubMed - indexed for MEDLINE]
Methylation gets into rhythm with NAD(+)-SIRT1.
Nat Struct Mol Biol. 2015 Apr;22(4):275-7
Authors: Tasselli L, Chua KF
Circadian regulation of epigenetic chromatin marks drives daily transcriptional oscillation of thousands of genes and is intimately linked to cellular metabolism and bioenergetics. New work links circadian fluctuations in the activity of the SIRT1 deacetylase, a sensor of the cellular energy state, to histone-methylation changes and the circadian expression of clock-controlled genes.
PMID: 25837871 [PubMed - indexed for MEDLINE]
Poor Sustained Virological Response in a Multicenter Real-Life Cohort of Chronic Hepatitis C Patients Treated with Pegylated Interferon and Ribavirin plus Telaprevir or Boceprevir.
Dig Dis Sci. 2015 Apr;60(4):1045-51
Authors: Vo KP, Vutien P, Akiyama MJ, Vu VD, Ha NB, Piotrowski JI, Wantuck J, Roytman MM, Tsai N, Cheung R, Li J, Nguyen MH
BACKGROUND: There are limited data analyzing the effectiveness of boceprevir (BOC) or telaprevir (TVR) in combination with pegylated interferon (PEG-IFN) plus ribavirin (RBV) in a real-life patient cohort.
AIMS: In clinical trials, patients with chronic hepatitis C (CHC) treated with BOC or TVR plus PEG-IFN and RBV achieved sustained virological response (SVR) rates of 70 %. However, it is not clear whether similar results can be realized in routine practice. Our goal is to examine SVR rates of these triple regimens for CHC in a multicenter real-life patient cohort.
METHODS: We retrospectively studied 200 consecutive CHC genotype 1 patients who were initiated on PEG-IFN, RBV, and either TVR (n = 113) or BOC (n = 87) from July 2011 to February 2014 at two US academic liver clinics, a Veterans Affairs liver clinic and a community gastroenterology clinic.
RESULTS: Both BOC and TVR treatment groups were similar in regard to comorbidities, BMI, and HCV RNA levels. BOC patients were more likely to have cirrhosis than TVR patients (47 vs. 24 %, P = 0.001). SVR rates were low in both cohorts (40 % for BOC, 53 % for TVR, P = 0.05). On multivariate logistic regression, treatment adherence by the "80/80/80 rule," diagnosis of cirrhosis, and use of erythropoietin were statistically significant predictors for SVR. Of these, treatment adherence was the strongest predictor (OR 4.43, 95 % CI 2.8-6.06, P < 0.001).
CONCLUSION: SVR was much lower in a real-life patient cohort than in clinical trials (53 % for TVR and 40 % for BOC, compared to 66-75 % in clinical trials).
PMID: 25821099 [PubMed - indexed for MEDLINE]
Loss of HIF-1α in the notochord results in cell death and complete disappearance of the nucleus pulposus.
PLoS One. 2014;9(10):e110768
Authors: Merceron C, Mangiavini L, Robling A, Wilson TL, Giaccia AJ, Shapiro IM, Schipani E, Risbud MV
The intervertebral disc (IVD) is one of the largest avascular organs in vertebrates. The nucleus pulposus (NP), a highly hydrated and proteoglycan-enriched tissue, forms the inner portion of the IVD. The NP is surrounded by a multi-lamellar fibrocartilaginous structure, the annulus fibrosus (AF). This structure is covered superior and inferior side by cartilaginous endplates (CEP). The NP is a unique tissue within the IVD as it results from the differentiation of notochordal cells, whereas, AF and CEP derive from the sclerotome. The hypoxia inducible factor-1α (HIF-1α) is expressed in NP cells but its function in NP development and homeostasis is largely unknown. We thus conditionally deleted HIF-1α in notochordal cells and investigated how loss of this transcription factor impacts NP formation and homeostasis at E15.5, birth, 1 and 4 months of age, respectively. Histological analysis, cell lineage studies, and TUNEL assay were performed. Morphologic changes of the mutant NP cells were identified as early as E15.5, followed, postnatally, by the progressive disappearance and replacement of the NP with a novel tissue that resembles fibrocartilage. Notably, lineage studies and TUNEL assay unequivocally proved that NP cells did not transdifferentiate into chondrocyte-like cells but they rather underwent massive cell death, and were completely replaced by a cell population belonging to a lineage distinct from the notochordal one. Finally, to evaluate the functional consequences of HIF-1α deletion in the NP, biomechanical testing of mutant IVD was performed. Loss of the NP in mutant mice significantly reduced the IVD biomechanical properties by decreasing its ability to absorb mechanical stress. These findings are similar to the changes usually observed during human IVD degeneration. Our study thus demonstrates that HIF-1α is essential for NP development and homeostasis, and it raises the intriguing possibility that this transcription factor could be involved in IVD degeneration in humans.
PMID: 25338007 [PubMed - indexed for MEDLINE]
Text mining for adverse drug events: the promise, challenges, and state of the art.
Drug Saf. 2014 Oct;37(10):777-90
Authors: Harpaz R, Callahan A, Tamang S, Low Y, Odgers D, Finlayson S, Jung K, LePendu P, Shah NH
Text mining is the computational process of extracting meaningful information from large amounts of unstructured text. It is emerging as a tool to leverage underutilized data sources that can improve pharmacovigilance, including the objective of adverse drug event (ADE) detection and assessment. This article provides an overview of recent advances in pharmacovigilance driven by the application of text mining, and discusses several data sources-such as biomedical literature, clinical narratives, product labeling, social media, and Web search logs-that are amenable to text mining for pharmacovigilance. Given the state of the art, it appears text mining can be applied to extract useful ADE-related information from multiple textual sources. Nonetheless, further research is required to address remaining technical challenges associated with the text mining methodologies, and to conclusively determine the relative contribution of each textual source to improving pharmacovigilance.
PMID: 25151493 [PubMed - indexed for MEDLINE]
Coping and glucocorticoid receptor regulation by stress inoculation.
Psychoneuroendocrinology. 2014 Nov;49:272-9
Authors: Lee AG, Buckmaster CL, Yi E, Schatzberg AF, Lyons DM
Intermittent exposure to mildly stressful situations provides opportunities to practice coping in the context of exposure psychotherapies and stress inoculation training. Previously, we showed that stress inoculation modeled in juvenile monkeys enhances subsequent indications of resilience. Here we examine stress inoculation effects in adult female monkeys. We found that stress inoculation prevents social separation stress induced anhedonia measured using sucrose preference tests and reduces the hypothalamic pituitary adrenal (HPA) axis stress hormone response to a novel environment. Stress inoculation also increases glucocorticoid receptor (NR3C1) gene expression in anterior cingulate cortex but not hippocampus. Increased anterior cingulate cortex NR3C1 expression induced by stress inoculation is not associated with significant changes in GR1F promoter DNA methylation. On average, low levels of promoter DNA methylation and limited GR1F expression were evident in monkey anterior cingulate cortex as observed in corticolimbic brain regions of adult humans. Taken together these findings suggest that stress inoculation in adulthood enhances behavioral and hormonal aspects of coping without significantly influencing GR1F promoter DNA methylation as a mechanism for NR3C1 transcription regulation.
PMID: 25127085 [PubMed - indexed for MEDLINE]
Gastric outlet obstruction caused by heterotopic pancreas in an adolescent.
Dig Dis Sci. 2015 Apr;60(4):835-7
Authors: Rodriguez AA, Berquist W, Bingham D
PMID: 25107445 [PubMed - indexed for MEDLINE]
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