Recent Stanford Publications in PubMed
- Early surgical intervention or watchful waiting for the management of asymptomatic mitral regurgitation: a systematic review and meta-analysis.Goldstone AB, Patrick WL, Cohen JE, Aribeana CN, Popat R, Woo YJAnn Cardiothorac Surg
- Mitral valve repair.Woo YJAnn Cardiothorac Surg
- Saving Supersick Patients Undergoing Liver Transplant.Melcher MLJAMA Surg
- Human B-cell isotype switching origins of IgE.Looney TJ, Lee JY, Roskin KM, Hoh RA, King J, Glanville J, Liu Y, Pham TD, Dekker CL, Davis MM, Boyd SDJ Allergy Clin Immunol
- Wnt Signaling During Cutaneous Wound Healing.Houschyar KS, Momeni A, Pyles MN, Maan ZN, Whittam AJ, Siemers FOrganogenesis
- Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS.Jovičić A, Mertens J, Boeynaems S, Bogaert E, Chai N, Yamada SB, Paul JW, Sun S, Herdy JR, Bieri G, Kramer NJ, Gage FH, Van Den Bosch L, Robberecht W, Gitler ADNat Neurosci
- Optogenetics: 10 years of microbial opsins in neuroscience.Deisseroth KNat Neurosci
- Optogenetics: 10 years after ChR2 in neurons-views from the community.Adamantidis A, Arber S, Bains JS, Bamberg E, Bonci A, Buzsáki G, Cardin JA, Costa RM, Dan Y, Goda Y, Graybiel AM, Häusser M, Hegemann P, Huguenard JR, Insel TR, Janak PH, Johnston D, Josselyn SA, Koch C, Kreitzer AC, Lüscher C, Malenka RC, Miesenböck G, Nagel G, Roska B, Schnitzer MJ, Shenoy KV, Soltesz I, Sternson SM, Tsien RW, Tsien RY, Turrigiano GG, Tye KM, Wilson RINat Neurosci
- Point-of-Care Ultrasound for the Detection of Traumatic Intracranial Hemorrhage in Infants: A Pilot Study.McCormick T, Chilstrom M, Childs J, McGarry R, Seif D, Mailhot T, Perera P, Kang T, Claudius IPediatr Emerg Care
- Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer.Pham TA, Gallo AM, Concepcion W, Esquivel CO, Bonham CAJAMA Surg
- Cysteine cathepsin activity suppresses osteoclastogenesis of myeloid-derived suppressor cells in breast cancer.Edgington-Mitchell LE, Rautela J, Duivenvoorden HM, Jayatilleke KM, van der Linden WA, Verdoes M, Bogyo M, Parker BSOncotarget
- Time-driven activity-based costing of multivessel coronary artery bypass grafting across national boundaries to identify improvement opportunities: study protocol.Erhun F, Mistry B, Platchek T, Milstein A, Narayanan VG, Kaplan RSBMJ Open
- Effect of Lipohypertrophy on Accuracy of Continuous Glucose Monitoring in Patients With Type 1 Diabetes.DeSalvo DJ, Maahs DM, Messer L, Wadwa RP, Payne S, Ly TT, Buckingham BADiabetes Care
- Perioperative Management of Antithrombotic Therapy in Common Otolaryngologic Surgical Procedures: State of the Art Review.Hsueh WD, Hwang PH, Abuzeid WMOtolaryngol Head Neck Surg
- Novel TIA biomarkers identified by mass spectrometry-based proteomics.George PM, Mlynash M, Adams CM, Kuo CJ, Albers GW, Olivot JMInt J Stroke
- Blending Cr2 O3 into a NiO-Ni Electrocatalyst for Sustained Water Splitting.Gong M, Zhou W, Kenney MJ, Kapusta R, Cowley S, Wu Y, Lu B, Lin MC, Wang DY, Yang J, Hwang BJ, Dai HAngew Chem Int Ed Engl
- Choosing Subsamples for Sequencing Studies by Minimizing the Average Distance to the Closest Leaf.Kang JT, Zhang P, Zöllner S, Rosenberg NAGenetics
- Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes.Karakikes I, Ameen M, Termglinchan V, Wu JCCirc Res
- Quo vadis, enzymology?Khosla CNat Chem Biol
- Intraocular pressure changes in emergent surgical decompression of orbital compartment syndrome.Mohammadi F, Rashan A, Psaltis A, Janisewicz A, Li P, El-Sawy T, Nayak JVJAMA Otolaryngol Head Neck Surg
- Critical Care Delivery: The Importance of Process of Care and ICU Structure to Improved Outcomes: An Update From the American College of Critical Care Medicine Task Force on Models of Critical Care.Weled BJ, Adzhigirey LA, Hodgman TM, Brilli RJ, Spevetz A, Kline AM, Montgomery VL, Puri N, Tisherman SA, Vespa PM, Pronovost PJ, Rainey TG, Patterson AJ, Wheeler DS, Task Force on Models for Critical CareCrit Care Med
- Radial nerve transection associated with closed humeral shaft fractures: a report of two cases and review of the literature.Leucht P, Ryu JH, Bellino MJJ Shoulder Elbow Surg
- The dawning age of genetic testing for sports injuries.Goodlin GT, Roos TR, Roos AK, Kim SKClin J Sport Med
- Photothermal effects and toxicity of Fe3O4 nanoparticles via near infrared laser irradiation for cancer therapy.Dunn AW, Ehsan SM, Mast D, Pauletti GM, Xu H, Zhang J, Ewing RC, Shi DMater Sci Eng C Mater Biol Appl
- The Ontology of Clinical Research (OCRe): an informatics foundation for the science of clinical research.Sim I, Tu SW, Carini S, Lehmann HP, Pollock BH, Peleg M, Wittkowski KMJ Biomed Inform
Early surgical intervention or watchful waiting for the management of asymptomatic mitral regurgitation: a systematic review and meta-analysis.
Ann Cardiothorac Surg. 2015 May;4(3):220-229
Authors: Goldstone AB, Patrick WL, Cohen JE, Aribeana CN, Popat R, Woo YJ
BACKGROUND: Discordance between studies drives continued debate regarding the best management of asymptomatic severe mitral regurgitation (MR). The aim of the present study was to conduct a systematic review and meta-analysis of management plans for asymptomatic severe MR, and compare the effectiveness of a strategy of early surgery to watchful waiting.
METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies were excluded if they: (I) lacked a watchful waiting cohort; (II) included symptomatic patients; or (III) included etiologies other than degenerative mitral valve disease. The primary outcome of the study was all-cause mortality at 10 years. Secondary outcomes included operative mortality, repair rate, repeat mitral valve surgery, and development of new atrial fibrillation.
RESULTS: Five observational studies were eligible for review and three were included in the pooled analysis. In asymptomatic patients without class I triggers (symptoms or ventricular dysfunction), pooled analysis revealed a significant reduction in long-term mortality with an early surgery approach [hazard ratio (HR) =0.38; 95% confidence interval (CI): 0.21-0.71]. This survival benefit persisted in a sub-group analysis limited to patients without class II triggers (atrial fibrillation or pulmonary hypertension) [relative risk (RR) =0.85; 95% CI: 0.75-0.98]. Aggregate rates of operative mortality did not differ between treatment arms (0.7% vs. 0.7% for early surgery vs. watchful waiting). However, significantly higher repair rates were achieved in the early surgery cohorts (RR =1.10; 95% CI: 1.02-1.18).
CONCLUSIONS: Despite disagreement between individual studies, the present meta-analysis demonstrates that a strategy of early surgery may improve survival and increase the likelihood of mitral valve repair compared with watchful waiting. Early surgery may also benefit patients when instituted prior to the development of class II triggers.
PMID: 26309823 [PubMed - as supplied by publisher]
Mitral valve repair.
Ann Cardiothorac Surg. 2015 May;4(3):219
Authors: Woo YJ
PMID: 26309822 [PubMed - as supplied by publisher]
Saving Supersick Patients Undergoing Liver Transplant.
JAMA Surg. 2015 Aug 26;
Authors: Melcher ML
PMID: 26309213 [PubMed - as supplied by publisher]
Human B-cell isotype switching origins of IgE.
J Allergy Clin Immunol. 2015 Aug 22;
Authors: Looney TJ, Lee JY, Roskin KM, Hoh RA, King J, Glanville J, Liu Y, Pham TD, Dekker CL, Davis MM, Boyd SD
BACKGROUND: B cells expressing IgE contribute to immunity against parasites and venoms and are the source of antigen specificity in allergic patients, yet the developmental pathways producing these B cells in human subjects remain a subject of debate. Much of our knowledge of IgE lineage development derives from model studies in mice rather than from human subjects.
OBJECTIVE: We evaluate models for isotype switching to IgE in human subjects using immunoglobulin heavy chain (IGH) mutational lineage data.
METHODS: We analyzed IGH repertoires in 9 allergic and 24 healthy adults using high-throughput DNA sequencing of 15,843,270 IGH rearrangements to identify clonal lineages of B cells containing members expressing IgE. Somatic mutations in IGH inherited from common ancestors within the clonal lineage are used to infer the relationships between B cells.
RESULTS: Data from 613,641 multi-isotype B-cell clonal lineages, of which 592 include an IgE member, are consistent with indirect switching to IgE from IgG- or IgA-expressing lineage members in human subjects. We also find that these inferred isotype switching frequencies are similar in healthy and allergic subjects.
CONCLUSIONS: We found evidence that secondary isotype switching of mutated IgG1-expressing B cells is the primary source of IgE in human subjects, with lesser contributions from precursors expressing other switched isotypes and rarely IgM or IgD, suggesting that IgE is derived from previously antigen-experienced B cells rather than naive B cells that typically express low-affinity unmutated antibodies. These data provide a basis from which to evaluate allergen-specific human antibody repertoires in healthy and diseased subjects.
PMID: 26309181 [PubMed - as supplied by publisher]
Wnt Signaling During Cutaneous Wound Healing.
Organogenesis. 2015 Aug 26;:0
Authors: Houschyar KS, Momeni A, Pyles MN, Maan ZN, Whittam AJ, Siemers F
Cutaneous wound repair in adult mammals typically does not regenerate original dermal architecture. Skin that has undergone repair following injury is not identical to intact uninjured skin. This disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development and thus we seek a deeper understanding of the role that Wnt signaling plays in the mechanisms of skin repair in both fetal and adult wounds. The influence of secreted Wnt signaling proteins in tissue homeostasis has galvanized efforts to identify small molecules that target Wnt-mediated cellular responses. Wnt signaling is activated by wounding and participates in every subsequent stage of the healing process from the control of inflammation and programmed cell death, to the mobilization of stem cell reservoirs within the wound site. Endogenous Wnt signaling augmentation represents an attractive option to aid in the restoration of cutaneous wounds, as the complex mechanisms of the Wnt pathway have been increasingly investigated over the years. In this review, we summarize recent data elucidating the roles that Wnt signaling plays in cutaneous wound healing process.
PMID: 26309090 [PubMed - as supplied by publisher]
Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS.
Nat Neurosci. 2015 Aug 26;18(9):1226-1229
Authors: Jovičić A, Mertens J, Boeynaems S, Bogaert E, Chai N, Yamada SB, Paul JW, Sun S, Herdy JR, Bieri G, Kramer NJ, Gage FH, Van Den Bosch L, Robberecht W, Gitler AD
C9orf72 mutations are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) produced by unconventional translation of the C9orf72 repeat expansions cause neurodegeneration in cell culture and in animal models. We performed two unbiased screens in Saccharomyces cerevisiae and identified potent modifiers of DPR toxicity, including karyopherins and effectors of Ran-mediated nucleocytoplasmic transport, providing insight into potential disease mechanisms and therapeutic targets.
PMID: 26308983 [PubMed - as supplied by publisher]
Optogenetics: 10 years of microbial opsins in neuroscience.
Nat Neurosci. 2015 Aug 26;18(9):1213-1225
Authors: Deisseroth K
Over the past 10 years, the development and convergence of microbial opsin engineering, modular genetic methods for cell-type targeting and optical strategies for guiding light through tissue have enabled versatile optical control of defined cells in living systems, defining modern optogenetics. Despite widespread recognition of the importance of spatiotemporally precise causal control over cellular signaling, for nearly the first half (2005-2009) of this 10-year period, as optogenetics was being created, there were difficulties in implementation, few publications and limited biological findings. In contrast, the ensuing years have witnessed a substantial acceleration in the application domain, with the publication of thousands of discoveries and insights into the function of nervous systems and beyond. This Historical Commentary reflects on the scientific landscape of this decade-long transition.
PMID: 26308982 [PubMed - as supplied by publisher]
Optogenetics: 10 years after ChR2 in neurons-views from the community.
Nat Neurosci. 2015 Aug 26;18(9):1202-1212
Authors: Adamantidis A, Arber S, Bains JS, Bamberg E, Bonci A, Buzsáki G, Cardin JA, Costa RM, Dan Y, Goda Y, Graybiel AM, Häusser M, Hegemann P, Huguenard JR, Insel TR, Janak PH, Johnston D, Josselyn SA, Koch C, Kreitzer AC, Lüscher C, Malenka RC, Miesenböck G, Nagel G, Roska B, Schnitzer MJ, Shenoy KV, Soltesz I, Sternson SM, Tsien RW, Tsien RY, Turrigiano GG, Tye KM, Wilson RI
PMID: 26308981 [PubMed - as supplied by publisher]
Point-of-Care Ultrasound for the Detection of Traumatic Intracranial Hemorrhage in Infants: A Pilot Study.
Pediatr Emerg Care. 2015 Aug 21;
Authors: McCormick T, Chilstrom M, Childs J, McGarry R, Seif D, Mailhot T, Perera P, Kang T, Claudius I
OBJECTIVES: Computed tomography is the criterion standard imaging modality to detect intracranial hemorrhage (ICH) in children and infants after closed head injury, but its use can be limited by patient instability, need for sedation, and risk of ionizing radiation exposure. Cranial ultrasound is used routinely to detect intraventricular hemorrhage in neonates. We sought to determine if point-of-care (POC) cranial ultrasound performed by emergency physicians can detect traumatic ICH in infants.
METHODS: Infants with ICH diagnosed by computed tomography were identified. For every infant with an ICH, 2 controls with symptoms and diagnoses unrelated to head trauma were identified. Point-of-care cranial ultrasound was performed by an emergency physician on all patients, and video clips were recorded. Two ultrasound fellowship-trained emergency physicians, blinded to the patients' diagnosis and clinical status, independently reviewed the ultrasound clips and determined the presence or absence of ICH.
RESULTS: Twelve patients were included in the study, 4 with ICH and 8 controls. Observer 1 identified ICH with 100% sensitivity (95% confidence interval [CI], 40%-100%) and 100% specificity (95% CI, 60%-100%). Observer 2 identified ICH with 50% sensitivity (95% CI, 9%-98%) and 87.5% specificity (95% CI, 47%-99%). Agreement between observers was 75%, κ = 0.4 (P = 0.079; 95% CI, 0-0.95).
CONCLUSIONS: Traumatic ICH can be identified with POC cranial ultrasound by ultrasound fellowship-trained emergency physicians. Although variations between observers and wide confidence intervals preclude drawing meaningful conclusions about sensitivity and specificity from this sample, these results support the need for further investigation into the role of POC cranial ultrasound.
PMID: 26308609 [PubMed - as supplied by publisher]
Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer.
JAMA Surg. 2015 Aug 26;
Authors: Pham TA, Gallo AM, Concepcion W, Esquivel CO, Bonham CA
Introduction: Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most common primary hepatic malignant neoplasms in childhood. Given the rarity of these childhood tumors and their propensity to present at advanced stages, updated long-term data are needed.
Objective: To determine the efficacy of liver transplant in children with HBL or HCC.
Design, Participants, and Setting: This single-institution retrospective medical record review and analysis spanned from January 1, 1997, through September 17, 2014, at Stanford University School of Medicine. A total of 40 patients younger than 18 years underwent liver transplant for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with follow-up until September 17, 2014. Patients who underwent transplant for HCC included those with tumors that were greater in size than what is proposed by the Milan (a single tumor measuring ≤5 cm or ≤3 nodules measuring ≤3 cm) and University of California, San Francisco (single tumor measuring ≤6.5 cm or ≤3 nodules measuring ≤4.5 cm and a total diameter of ≤8 cm), criteria.
Main Outcomes and Measures: Disease-free and overall patient survival and graft survival.
Results: Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year disease-free survival after liver transplant was 93%, 82%, and 82%, respectively, for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients with HCC. Risk factors associated with HBL recurrence after transplant included having pretreatment extent of disease stage IV lesions and a longer waiting list time and being older at the time of the transplant. Recurrence was found in 2 of 7 patients with HBL and pretransplant metastases, which were not found to be an independent risk factor for recurrence. Patients with HCC larger than the proposed Milan and University of California, San Francisco, criteria experienced good 5-year disease-free (82%) and overall (78%) survival after transplant. Being older at the time of transplant (18 vs 11 years; P = .04) and the presence of metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor recurrence.
Conclusions and Relevance: Liver transplant combined with chemotherapy is an excellent treatment that provides long-term disease-free survival in children diagnosed with advanced HBL and HCC. Early addition to a waiting list and aggressive multimodal therapy provide excellent results. Transplant should still be considered in children with HCC larger than the Milan and University of California, San Francisco, criteria.
PMID: 26308249 [PubMed - as supplied by publisher]
Cysteine cathepsin activity suppresses osteoclastogenesis of myeloid-derived suppressor cells in breast cancer.
Oncotarget. 2015 Jul 17;
Authors: Edgington-Mitchell LE, Rautela J, Duivenvoorden HM, Jayatilleke KM, van der Linden WA, Verdoes M, Bogyo M, Parker BS
Cysteine cathepsin proteases contribute to many normal cellular functions, and their aberrant activity within various cell types can contribute to many diseases, including breast cancer. It is now well accepted that cathepsin proteases have numerous cell-specific functions within the tumor microenvironment that function to promote tumor growth and invasion, such that they may be valid targets for anti-metastatic therapeutic approaches. Using activity-based probes, we have examined the activity and expression of cysteine cathepsins in a mouse model of breast cancer metastasis to bone. In mice bearing highly metastatic tumors, we detected abundant cysteine cathepsin expression and activity in myeloid-derived suppressor cells (MDSCs). These immature immune cells have known metastasis-promoting roles, including immunosuppression and osteoclastogenesis, and we assessed the contribution of cysteine cathepsins to these functions. Blocking cysteine cathepsin activity with multiple small-molecule inhibitors resulted in enhanced differentiation of multinucleated osteoclasts. This highlights a potential role for cysteine cathepsin activity in suppressing the fusion of osteoclast precursor cells. In support of this hypothesis, we found that expression and activity of key cysteine cathepsins were downregulated during MDSC-osteoclast differentiation. Another cysteine protease, legumain, also inhibits osteoclastogenesis, in part through modulation of cathepsin L activity. Together, these data suggest that cysteine protease inhibition is associated with enhanced osteoclastogenesis, a process that has been implicated in bone metastasis.
PMID: 26308073 [PubMed - as supplied by publisher]
Time-driven activity-based costing of multivessel coronary artery bypass grafting across national boundaries to identify improvement opportunities: study protocol.
BMJ Open. 2015;5(8):e008765
Authors: Erhun F, Mistry B, Platchek T, Milstein A, Narayanan VG, Kaplan RS
INTRODUCTION: Coronary artery bypass graft (CABG) surgery is a well-established, commonly performed treatment for coronary artery disease-a disease that affects over 10% of US adults and is a major cause of morbidity and mortality. In 2005, the mean cost for a CABG procedure among Medicare beneficiaries in the USA was $32 201±$23 059. The same operation reportedly costs less than $2000 to produce in India. The goals of the proposed study are to (1) identify the difference in the costs incurred to perform CABG surgery by three Joint Commission accredited hospitals with reputations for high quality and efficiency and (2) characterise the opportunity to reduce the cost of performing CABG surgery.
METHODS AND ANALYSIS: We use time-driven activity-based costing (TDABC) to quantify the hospitals' costs of producing elective, multivessel CABG. TDABC estimates the costs of a given clinical service by combining information about the process of patient care delivery (specifically, the time and quantity of labour and non-labour resources utilised to perform each activity) with the unit cost of each resource used to provide the care. Resource utilisation was estimated by constructing CABG process maps for each site based on observation of care and staff interviews. Unit costs were calculated as a capacity cost rate, measured as a $/min, for each resource consumed in CABG production. Multiplying together the unit costs and resource quantities and summing across all resources used will produce the average cost of CABG production at each site. We will conclude by conducting a variance analysis of labour costs to reveal opportunities to bend the cost curve for CABG production in the USA.
ETHICS AND DISSEMINATION: All our methods were exempted from review by the Stanford Institutional Review Board. Results will be published in peer-reviewed journals and presented at scientific meetings.
PMID: 26307621 [PubMed - in process]
Effect of Lipohypertrophy on Accuracy of Continuous Glucose Monitoring in Patients With Type 1 Diabetes.
Diabetes Care. 2015 Aug 25;
Authors: DeSalvo DJ, Maahs DM, Messer L, Wadwa RP, Payne S, Ly TT, Buckingham BA
PMID: 26307604 [PubMed - as supplied by publisher]
Perioperative Management of Antithrombotic Therapy in Common Otolaryngologic Surgical Procedures: State of the Art Review.
Otolaryngol Head Neck Surg. 2015 Aug 25;
Authors: Hsueh WD, Hwang PH, Abuzeid WM
OBJECTIVE: The perioperative management of patients undergoing otolaryngologic procedures is increasingly complicated by the use of newer antithrombotic agents. Furthermore, with advances in anesthesia and surgical technique, otolaryngologists are presented with the challenge of operating on patients with advanced comorbid diseases. The objective of this review is to provide evidence-based recommendations on perioperative antithrombotic management for common otolaryngologic procedures.
DATA SOURCES: PubMed/MEDLINE.
REVIEW METHODS: Selected literature on patient-specific thromboembolic risk, rate of bleeding complications in otolaryngologic procedures, and the interruption of antithrombotic therapy is reviewed and interpreted by expert opinion.
CONCLUSIONS: By stratifying patients into either low thromboembolic risk (≤5%) or high thromboembolic risk (>5%) and interpreting this in the context of procedural bleed risk and potential clinical consequences in the event of a bleed, otolaryngologists can make evidence-based decisions to determine the appropriate perioperative management of antithrombotic therapy.
IMPLICATIONS FOR PRACTICE: When the perioperative management of antithrombotic therapy is being decided, 3 critical factors must be considered systematically: the patient's inherent thromboembolic risk, the risk and potential consequences of bleeding related to the procedure, and the timing of interruption of thromboembolic therapy.
PMID: 26307580 [PubMed - as supplied by publisher]
Novel TIA biomarkers identified by mass spectrometry-based proteomics.
Int J Stroke. 2015 Aug 26;
Authors: George PM, Mlynash M, Adams CM, Kuo CJ, Albers GW, Olivot JM
BACKGROUND: Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment.
AIM: Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics.
METHODS: Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen.
RESULTS: Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found.
CONCLUSIONS: Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum biomarker for transient ischemic attack. This unbiased proteomic approach may be a promising method to identify novel biomarkers to more precisely diagnose transient ischemic attacks.
PMID: 26307429 [PubMed - as supplied by publisher]
Blending Cr2 O3 into a NiO-Ni Electrocatalyst for Sustained Water Splitting.
Angew Chem Int Ed Engl. 2015 Aug 24;
Authors: Gong M, Zhou W, Kenney MJ, Kapusta R, Cowley S, Wu Y, Lu B, Lin MC, Wang DY, Yang J, Hwang BJ, Dai H
The rising H2 economy demands active and durable electrocatalysts based on low-cost, earth-abundant materials for water electrolysis/photolysis. Here we report nanoscale Ni metal cores over-coated by a Cr2 O3 -blended NiO layer synthesized on metallic foam substrates. The Ni@NiO/Cr2 O3 triphase material exhibits superior activity and stability similar to Pt for the hydrogen-evolution reaction in basic solutions. The chemically stable Cr2 O3 is crucial for preventing oxidation of the Ni core, maintaining abundant NiO/Ni interfaces as catalytically active sites in the heterostructure and thus imparting high stability to the hydrogen-evolution catalyst. The highly active and stable electrocatalyst enables an alkaline electrolyzer operating at 20 mA cm(-2) at a voltage lower than 1.5 V, lasting longer than 3 weeks without decay. The non-precious metal catalysts afford a high efficiency of about 15 % for light-driven water splitting using GaAs solar cells.
PMID: 26307213 [PubMed - as supplied by publisher]
Choosing Subsamples for Sequencing Studies by Minimizing the Average Distance to the Closest Leaf.
Genetics. 2015 Aug 24;
Authors: Kang JT, Zhang P, Zöllner S, Rosenberg NA
Imputation of genotypes in a study sample can make use of sequenced or densely genotyped external reference panels consisting of individuals that are not from the study sample. It can also employ internal reference panels, incorporating a subset of individuals from the study sample itself. Internal panels offer an advantage over external panels, as they can reduce imputation errors arising from genetic dissimilarity between a population of interest and a second, distinct population from which the external reference panel has been constructed. As the cost of next-generation sequencing decreases, internal reference panel selection is becoming increasingly feasible. However, it is not clear how best to select individuals to include in such panels. We introduce a new method for selecting an internal reference panel-minimizing the average distance to the closest leaf (ADCL)-and compare its performance relative to an earlier algorithm: maximizing phylogenetic diversity (PD). Employing both simulated data and sequences from the 1000 Genomes Project, we show that ADCL provides a significant improvement in imputation accuracy, especially for imputation of sites with low-frequency alleles. This improvement in imputation accuracy is robust to changes in reference panel size, marker density, and length of the imputation target region.
PMID: 26307072 [PubMed - as supplied by publisher]
Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes.
Circ Res. 2015 Jun 19;117(1):80-8
Authors: Karakikes I, Ameen M, Termglinchan V, Wu JC
Disease models are essential for understanding cardiovascular disease pathogenesis and developing new therapeutics. The human induced pluripotent stem cell (iPSC) technology has generated significant enthusiasm for its potential application in basic and translational cardiac research. Patient-specific iPSC-derived cardiomyocytes offer an attractive experimental platform to model cardiovascular diseases, study the earliest stages of human development, accelerate predictive drug toxicology tests, and advance potential regenerative therapies. Harnessing the power of iPSC-derived cardiomyocytes could eliminate confounding species-specific and interpersonal variations and ultimately pave the way for the development of personalized medicine for cardiovascular diseases. However, the predictive power of iPSC-derived cardiomyocytes as a valuable model is contingent on comprehensive and rigorous molecular and functional characterization.
PMID: 26089365 [PubMed - indexed for MEDLINE]
Quo vadis, enzymology?
Nat Chem Biol. 2015 Jul;11(7):438-41
Authors: Khosla C
PMID: 26083060 [PubMed - indexed for MEDLINE]
Intraocular pressure changes in emergent surgical decompression of orbital compartment syndrome.
JAMA Otolaryngol Head Neck Surg. 2015 Jun;141(6):562-5
Authors: Mohammadi F, Rashan A, Psaltis A, Janisewicz A, Li P, El-Sawy T, Nayak JV
IMPORTANCE: Orbital compartment syndrome is an acute rise in intraorbital volume resulting in increased intraorbital pressure and possible ischemic compromise of the optic nerve. Tonometric pressure measurement of intraocular pressure can aid surgeons in the diagnosis of this condition and in choosing the need to proceed with emergent surgical intervention. In addition, we present an unexpected cause of orbital compartment syndrome following routine frontal sinus irrigation.
OBSERVATIONS: An emergent lateral canthotomy and cantholysis followed by endoscopic medial wall decompression were performed, with intraocular pressure measurements performed throughout the evolution of this successful, and vision sparing, set of procedures. The techniques and continuous improvements in intraocular pressure measurements are described.
CONCLUSIONS AND RELEVANCE: There are only rare reports of the progression of intraocular pressure prior to, and concurrent with, surgical orbital decompression. While no absolute threshold for intraocular pressure exists for when surgical decompression should be performed, the decision of when and which decompression procedures to undertake should be based on clinical judgment and experience. Availability of tonometry in the operating room serves to measure response to management in these rare but challenging settings where intervention may be required to prevent irreversible visual loss.
PMID: 25880995 [PubMed - indexed for MEDLINE]
Critical Care Delivery: The Importance of Process of Care and ICU Structure to Improved Outcomes: An Update From the American College of Critical Care Medicine Task Force on Models of Critical Care.
Crit Care Med. 2015 Jul;43(7):1520-5
Authors: Weled BJ, Adzhigirey LA, Hodgman TM, Brilli RJ, Spevetz A, Kline AM, Montgomery VL, Puri N, Tisherman SA, Vespa PM, Pronovost PJ, Rainey TG, Patterson AJ, Wheeler DS, Task Force on Models for Critical Care
In 2001, the Society of Critical Care Medicine published practice model guidelines that focused on the delivery of critical care and the roles of different ICU team members. An exhaustive review of the additional literature published since the last guideline has demonstrated that both the structure and process of care in the ICU are important for achieving optimal patient outcomes. Since the publication of the original guideline, several authorities have recognized that improvements in the processes of care, ICU structure, and the use of quality improvement science methodologies can beneficially impact patient outcomes and reduce costs. Herein, we summarize findings of the American College of Critical Care Medicine Task Force on Models of Critical Care: 1) An intensivist-led, high-performing, multidisciplinary team dedicated to the ICU is an integral part of effective care delivery; 2) Process improvement is the backbone of achieving high-quality ICU outcomes; 3) Standardized protocols including care bundles and order sets to facilitate measurable processes and outcomes should be used and further developed in the ICU setting; and 4) Institutional support for comprehensive quality improvement programs as well as tele-ICU programs should be provided.
PMID: 25803647 [PubMed - indexed for MEDLINE]
Radial nerve transection associated with closed humeral shaft fractures: a report of two cases and review of the literature.
J Shoulder Elbow Surg. 2015 Apr;24(4):e96-100
Authors: Leucht P, Ryu JH, Bellino MJ
PMID: 25660240 [PubMed - indexed for MEDLINE]
The dawning age of genetic testing for sports injuries.
Clin J Sport Med. 2015 Jan;25(1):1-5
Authors: Goodlin GT, Roos TR, Roos AK, Kim SK
PMID: 25536480 [PubMed - indexed for MEDLINE]
Photothermal effects and toxicity of Fe3O4 nanoparticles via near infrared laser irradiation for cancer therapy.
Mater Sci Eng C Mater Biol Appl. 2015 Jan;46:97-102
Authors: Dunn AW, Ehsan SM, Mast D, Pauletti GM, Xu H, Zhang J, Ewing RC, Shi D
The photothermal effect of magnetite (Fe3O4) nanoparticles was characterized by photonic absorption in the near-infrared (NIR) region. Upon laser irradiation at 785 nm, the Fe3O4 nanoparticles generate localized hyperthermia in tumorous lesions, which is an effective strategy for cancer therapy; however, uncoated magnetite possesses an innate toxicity which can lead to drawbacks in the clinical setting. To reduce innate toxicity, a poly(acrylic acid) (PAA) coating on the nanoparticles was investigated in order to determine the alterations to stability and the degree of toxicity in an attempt to create a higher utility vector. It was found that the PAA coating significantly reduced the innate toxicity of the uncoated magnetite. Furthermore, the efficacy of PAA-coated magnetite nanoparticles (PAA-Fe3O4) was investigated for treating MDA-MB-231 (human mammary gland adenocarcinoma) cultures in viable concentration ranges (0.1-0.5mg/ml). An appropriate PAA-Fe3O4 concentration range was then established for inducing significant cell death by hyperthermic ablation, but not through innate toxicity.
PMID: 25491964 [PubMed - indexed for MEDLINE]
The Ontology of Clinical Research (OCRe): an informatics foundation for the science of clinical research.
J Biomed Inform. 2014 Dec;52:78-91
Authors: Sim I, Tu SW, Carini S, Lehmann HP, Pollock BH, Peleg M, Wittkowski KM
To date, the scientific process for generating, interpreting, and applying knowledge has received less informatics attention than operational processes for conducting clinical studies. The activities of these scientific processes - the science of clinical research - are centered on the study protocol, which is the abstract representation of the scientific design of a clinical study. The Ontology of Clinical Research (OCRe) is an OWL 2 model of the entities and relationships of study design protocols for the purpose of computationally supporting the design and analysis of human studies. OCRe's modeling is independent of any specific study design or clinical domain. It includes a study design typology and a specialized module called ERGO Annotation for capturing the meaning of eligibility criteria. In this paper, we describe the key informatics use cases of each phase of a study's scientific lifecycle, present OCRe and the principles behind its modeling, and describe applications of OCRe and associated technologies to a range of clinical research use cases. OCRe captures the central semantics that underlies the scientific processes of clinical research and can serve as an informatics foundation for supporting the entire range of knowledge activities that constitute the science of clinical research.
PMID: 24239612 [PubMed - indexed for MEDLINE]
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