Defects Healing of the ZnO Surface by Filling with Au Atom Catalysts for Efficient Photocatalytic H2 Production.

Healed defects on photocatalysts surface and their interaction with plasmonic nanoparticles (NPs) have attracted attention in H2 production process. In this study, surface oxygen vacancy (Vo ) defects are created on ZnO (Vo -ZnO) NPs by directly pyrolyzing zeolitic imidazolate framework. The surface defects on Vo -ZnO provide active sites for the diffusion of single Au atoms and as nucleation sites for the formation of Au NPs by the in situ photodeposition process. The electronically healed surface defects by single Au atoms help in the formation of a heterojunction between the ZnO and plasmonic Au NPs. The formed Au/Vo -Au:ZnO-4 heterojunction prolongs photoelectron lifetimes and increases donor charge density. Therefore, the optimized photocatalysts of Au/Vo -Au:ZnO-4 has 21.28 times higher H2 production rate than the pristine Vo -ZnO under UV-visible light in 0.35 m Na2 SO4 and 0.25 m Na2 SO3 . However in 0.35 m Na2 S and 0.25 m Na2 SO3 , the H2 production rate is 25.84 mmole h-1 g-1 . Furthermore, Au/Vo -Au:ZnO-4 shows visible light activity by generating hot carries via induced surface plasmonic effects. It has 48.58 times higher H2 production rate than pristine Vo -ZnO. Therefore, this study infers new insight for defect healing mediated preparation of Au/Vo -Au:ZnO heterojunction for efficient photocatalytic H2 production.

The impact of early cryoballoon ablation on clinical outcome in patients with atrial fibrillation: From the Korean cryoballoon ablation registry.

INTRODUCTION: Influence of early atrial fibrillation (AF) ablation, particularly cryoballoon ablation (CBA), on clinical outcome during long-term follow-up has not been clarified. The objective was to determine whether an early CBA (diagnosis-to-ablation of ≤6 months) strategy could affect freedom from AF recurrence after index CBA. METHODS: The study included 2605 patients from Korean CBA registry data with follow-up >12 months after de novo CBA. The primary outcome was recurrence of atrial tachyarrhythmias (ATs) of ≥30-s after a 3-month blanking period. RESULTS: Compared to patients in early CBA group, patients in late CBA group had higher prevalence of diabetes, congestive heart failure, and chronic kidney disease, and higher mean CHA2 DS2 -VAS score. During mean follow-up of >21 months, ATs recurrence was detected in 839 (32.2%) patients. The early CBA group showed a significantly lower 2-year recurrence rate of ATs than the late CBA group (26.1% vs. 31.7%, p = 0.043). In subgroup analysis, the early CBA group showed significantly higher 1-year and 2-year freedom from ATs recurrence than the late CBA group only in paroxysmal atrial fibrillation (PAF) patients in overall and propensity score matched cohorts. Multivariate analysis showed that early CBA was an independent factor for preventing ATs recurrence in PAF (hazard ratio: 0.637; 95% confidence intervals: 0.412-0.984). CONCLUSION: Early CBA strategy, resulting in significantly lower ATs recurrence during 2-year follow-up after index CBA, might be considered as an initial rhythm control therapy in patients with paroxysmal AF.

Timing of critical isthmus from end of P wave and usefulness of activation mapping with window of interest from end to end of P wave in reentrant atrial tachycardia.

In activation mapping of reentrant atrial tachycardia (AT), there was no reference for window of interest (WOI). We examined the timing of a successful termination site from end of the P wave and attempted to determine whether the critical isthmus can be identified using activation mapping when WOI was set as end to end of the P wave. Forty patients with 54 reentrant AT who underwent 3D electroanatomic mapping and radiofrequency catheter ablation were evaluated retrospectively. The critical isthmus was defined as a successful termination site. We evaluate critical isthmus timing from end of the P wave and percentage of critical isthmus timing from end of the P wave to tachycardia cycle length. In 54 reentrant AT, Macro-reentry was identified in 46 (85.2%) and micro-reentry was identified in eight (14.8%). The timing of the critical isthmus site from end of the P wave was - 4.0 ± 31.1 ms (Macro-reentry vs. Micro-reentry; - 8.9 ± 29.4 ms vs. 24.0 ± 26.7 ms; P = 0.005). The percentage of critical isthmus timing from end of the P wave/tachycardia cycle length was - 1.4 ± 10.5% (Macro-reentry vs. Micro-reentry; - 3.1 ± 9.8% vs. 8.3 ± 9.3%, P = 0.004) The critical isthmus of reentrant AT is located within 10% backward and forward from end of the P wave to tachycardia cycle length. Setting the WOI from end to end of the P wave is useful for identification of the critical isthmus through activation mapping.

Increased Mobility and Reduced Hysteresis of MoS2 Field-Effect Transistors via Direct Surface Precipitation of CsPbBr3-Nanoclusters for Charge Transfer Doping.

Transition-metal dichalcogenides (TMDs) and metal halide perovskites (MHPs) have been investigated for various applications, owing to their unique physical properties and excellent optoelectronic functionalities. TMD monolayers synthesized via chemical vapor deposition (CVD), which are advantageous for large-area synthesis, exhibit low mobility and prominent hysteresis in the electrical signals of field-effect transistors (FETs) because of their native defects. In this study, we demonstrate an increase in electrical mobility by ∼170 times and reduced hysteresis in the current-bias curves of MoS2 FETs hybridized with CsPbBr3 for charge transfer doping, which is implemented via solution-based CsPbBr3-nanocluster precipitation on CVD-grown MoS2 monolayer FETs. Electrons injected from CsPbBr3 into MoS2 induce heavy n-doping and heal point defects in the MoS2 channel layer, thus significantly increasing mobility and reducing hysteresis in the hybrid FETs. Our results provide a foundation for improving the reliability and performance of TMD-based FETs by hybridizing them with solution-based perovskites.

Axion Dark Matter Search around 4.55 µeV with Dine-Fischler-Srednicki-Zhitnitskii Sensitivity.

We report an axion dark matter search at Dine-Fischler-Srednicki-Zhitnitskii sensitivity with the CAPP-12TB haloscope, assuming axions contribute 100% of the local dark matter density. The search excluded the axion-photon coupling g_{aγγ} down to about 6.2×10^{-16} GeV^{-1} over the axion mass range between 4.51 and 4.59 µeV at a 90% confidence level. The achieved experimental sensitivity can also exclude Kim-Shifman-Vainshtein-Zakharov axion dark matter that makes up just 13% of the local dark matter density. The CAPP-12TB haloscope will continue the search over a wide range of axion masses.

The association of cardiac troponin and cardiovascular events in patients with concomitant heart failure preserved ejection fraction and atrial fibrillation.

BACKGROUND: Limited data are available for risk stratification in patients with atrial fibrillation (AF) and combined heart failure with preserved ejection fraction (HFpEF). We aimed to explore the prognostic utility of high-sensitivity cardiac troponin I (hs-cTnI) in patients with newly detected AF and concomitant HFpEF. METHODS: From August 2014 to December 2016, 2,361 patients with newly detected AF were polled in a retrospective single-center registry. Of which, 634 patients were eligible for HFpEF diagnosis (HFA-PEFF score ≥ 5) and 165 patients were excluded with exclusion criteria. Finally, 469 patients are classified into elevated or non-elevated hs-cTnI groups based on the 99th percentile upper reference limit (URL). The primary outcome was the incidence of major adverse cardiac and cerebrovascular events (MACCE) during follow-up. RESULTS: In 469 patients, 295 were stratified into the non-elevated hs-cTnI group (< 99th percentile URL of hs-cTnI) and 174 were placed in the elevated hs-cTnI group (≥ 99th percentile URL of hs-cTnI). The median follow-up period was 24.2 (interquartile range, 7.5-38.6) months. During the follow-up period, 106 patients (22.6%) in the study population experienced MACCE. In a multivariable Cox regression model, the elevated hs-cTnI group had a higher incidence of MACCE (adjusted hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.08-2.55; p = 0.03) and coronary revascularization-caused readmission (adjusted HR, 3.86; 95% CI, 1.39-15.09; p = 0.02) compared with the non-elevated hs-cTnI group. The incidence of heart failure-caused readmission tended to occur more frequently in the elevated hs-cTnI group (8.5% versus 15.5%; adjusted HR, 1.52; 95% CI, 0.86-2.67; p = 0.08). CONCLUSIONS: One-fifth of patients with AF and concomitant HFpEF experienced MACCE during follow-up, and elevated hs-cTnI was independently associated with higher risk of MACCE, as driven by heart failure and revascularization-caused readmission. This finding suggested that hs-cTnI may be a useful tool in individualized risk stratification of future cardiovascular events in patients with AF and concomitant HFpEF.

Association of right bundle branch block or intraventricular conduction delay with recurrence of atrial fibrillation after catheter ablation.

BACKGROUND: The association between bundle branch block (BBB) and recurrence of atrial fibrillation (AF) after catheter ablation is unclear. The aim of this study was to determine whether AF combined with BBB is associated with AF recurrence after catheter ablation. METHODS: A total of 477 consecutive AF patients who underwent catheter ablation were included. The AF patients were divided into three groups according to BBB: AF without BBB (n = 427), AF with right bundle branch block (AF with RBBB) (n = 16), and AF with intraventricular conduction delay (AF with IVCD) (n = 34). RESULTS: Of the 477 AF patients (mean age 57 years, 81% men, median CHA2 DS2 -VASc score of 1), 16 (3.4%) patients had RBBB, and 34 (7.1%) patients had IVCD. During a mean follow-up of 15.2 ± 6.7 months, 119 patients (24.9%) had recurrence of AF. Of these, 111 (26%) patients were in the AF without BBB group, with 2 (12.5%) and 6 (17.6%) patients in the RBBB and IVCD groups, respectively. The Kaplan-Meier estimate of the rate of recurrent AF was not significantly different among the three groups (p = .39). Multivariable analysis showed that persistent AF (HR 1.7, 95% CI 1.15-2.50, p = .007), chronic kidney disease (HR 2.94, 95% CI 1.20-7.17, p = .01), and left atrial diameter (HR 1.04, 95% CI 1.009-1.082, p = .01) were significantly associated with AF recurrence. CONCLUSION: AF with BBB was not significantly associated with the recurrence of AF after catheter ablation in middle-aged patients with low-risk cardiovascular profile.

Simulation of the optical system in the GroundBIRD telescope.

GroundBIRD is a ground-based telescope for measuring the polarization of cosmic microwave background radiation, and it is soon to be operational at the Teide Observatory. The GroundBIRD telescope employs Mizuguchi-Dragone dual reflectors and 161 kinetic inductance detectors coupled with single polarization antennas as photon detectors. We present the results of our optical simulation on the pointing direction, stray light response, and influence of the blackbody radiation from the baffle. We also find that the power of the baffle radiation incident on the detectors is reduced by 99.95% when corrugated feed horns are coupled to the detectors.

Wheeze trajectories: Determinants and outcomes in the CHILD Cohort Study.

BACKGROUND: Wheezing in early life is associated with asthma in adulthood; however, the determinants of wheezing trajectories and their associations with asthma and lung function in childhood remain poorly understood. OBJECTIVE: In the CHILD Cohort Study, we aimed to identify wheezing trajectories and examine the associations between these trajectories, risk factors, and clinical outcomes at age 5 years. METHODS: Wheeze data were collected at 8 time points from 3 months to 5 years of age. We used group-based trajectory models to derive wheeze trajectories among 3154 children. Associations with risk factors and clinical outcomes were analyzed by weighted regression models. RESULTS: We identified 4 trajectories: a never/infrequent trajectory, transient wheeze, intermediate-onset (preschool) wheeze, and persistent wheeze. Higher body mass index was a common risk factor for all wheeze trajectories compared with that in the never/infrequent group. The unique predictors for specific wheeze trajectories included male sex, lower respiratory tract infections, and day care attendance for transient wheeze; paternal history of asthma, atopic sensitization, and child genetic risk score of asthma for intermediate wheeze; and maternal asthma for persistent wheeze. Blood eosinophil counts were higher in children with the intermediate wheeze trajectory than in those children with the other trajectories at the ages of 1 and 5 years. All wheeze trajectories were associated with decreased lung function and increased risk of asthma at age 5 years. CONCLUSIONS: We identified 4 distinct trajectories in children from 3 months to 5 years of age, reflecting different phenotypes of early childhood wheeze. These trajectories were characterized by different biologic and physiologic traits and risk factors.

Poly(styrene sulfonic acid)-Grafted Carbon Black Synthesized by Surface-Initiated Atom Transfer Radical Polymerization.

Owing to their excellent electrical conductivity and robust mechanical properties, carbon-based nanocomposites are being used in a wide range of applications and devices, such as electromagnetic wave interference shielding, electronic devices, and fuel cells. While several approaches have been developed for synthesizing carbon nanotubes and carbon-black-based polymer nanocomposites, most studies have focused on the simple blending of the carbon material with a polymer matrix. However, this results in uncontrolled interactions between the carbon filler and the polymer chains, leading to the agglomeration of the carbon filler. Herein, we report a new strategy for synthesizing sulfonated polystyrene (PSS)-grafted carbon black nanoparticles (NPs) via surface-initiated atom-transfer radical polymerization. Treatments with O2 plasma and H2O2 result in the effective attachment of the appropriate initiator to the carbon black NPs, thus allowing for the controlled formation of the PSS brushes. The high polymeric processability and desirable mechanical properties of the PSS-grafted carbon black NPs enable them suitable for use in nonfluorinated-hydrocarbon-based polymer electrolyte membranes for fuel cells, which must exhibit high proton conductivity without interrupting the network of channels consisting of ionic clusters (i.e., sulfonic acid moieties).

The Role of Race and Insurance Status in Access to Genetic Counseling and Testing Among High-Risk Breast Cancer Patients.

PURPOSE: The role of germline genetic testing in breast cancer patients is crucial, especially in the setting of the recent trials showing the benefit of PARP inhibitors. The goal of this study was to identify racial disparities in genetic counseling and testing in patients with high-risk breast cancer. METHODS: Patients with 2 unique breast cancer diagnoses were examined to understand demographics, insurance coverage, characteristics of breast cancer, and whether they were recommended for and received genetic counseling and testing. RESULTS: A total of 69 patients with a dual diagnosis of breast cancer between the years 2000 and 2017 were identified (42% identified as White compared to 58% that identified as non-White). White patients were more likely to be recommended for genetic counseling (OR = 2.85; 95% CI, 1.07-7.93, P < .05), be referred for genetic counseling (OR = 3.17; 95% CI, 1.19-8.86, P < .05), receive counseling (OR = 3.82; 95% CI, 1.42-10.83, P < .01), and undergo genetic testing (OR = 2.88; 95% CI, 0.97-9.09, P = .056) compared to non-White patients. Patients with private insurance were significantly more likely to be recommended for genetic counseling (OR 5.63, P < .005), referred (OR 6.11, P < .005), receive counseling (OR 4.21, P < .05), and undergo testing (OR 4.10, P < .05). When controlled for insurance, there was no significant racial differences in the rates of GC recommendation, referral, counseling, or testing. CONCLUSION: The findings of this study suggest that disparities in genetic counseling and testing are largely driven by differences in health insurance.

The efficacy of single-lead implantable cardioverter-defibrillator with atrial sensing dipole to detect atrial fibrillation and to reduce inappropriate therapy according to atrial sensing ON or OFF: Rationale and design of the SMART-CONTROL study, a prospective multicenter randomized trial.

BACKGROUND: Few studies have compared the efficacy of single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (VDD-ICD) and conventional single-chamber ICD from the aspect of atrial fibrillation (AF) detection or inappropriate ICD therapy reduction. In the SMART-CONTROL trial (NCT03932604), we primarily aim to investigate whether the atrial sensing capability of VDD-ICD is useful in AF detection and inappropriate therapy reduction by randomly activating or deactivating the atrial sensing function. METHODS AND DESIGN: This study was designed as a prospective, multicenter, open-label, randomized trial to enroll 640 patients with no history of clinical AF or rhythm control for AF within 1 year who were undergoing the implantation of VDD-ICD system. Patients are assigned randomly to atrial sensing "ON" or "OFF" group, with crossover allowed during follow-up. The coprimary outcomes are the incidence of AF detection and inappropriate ICD therapy over a 2-year follow-up period. The secondary outcomes include non-AF atrial tachyarrhythmia, ventricular tachyarrhythmia with or without ICD therapy, thromboembolic events, bleeding, heart failure hospitalization, mortality, a composite of adverse cardiovascular events, and long-term atrial sensing stability or variability. CONCLUSION: We expect that this trial can evaluate the efficacy of a single-lead ICD system on various clinical outcomes including AF detection and inappropriate therapy reduction, and ultimately provide guidance to selection of ICD system.

Novel MicroRNA-Regulated Transcript Networks Are Associated with Chemotherapy Response in Ovarian Cancer.

High-grade serous ovarian cancer (HGSOC) is a highly lethal gynecologic cancer, in part due to resistance to platinum-based chemotherapy reported among 20% of patients. This study aims to generate novel hypotheses of the biological mechanisms underlying chemotherapy resistance, which remain poorly understood. Differential expression analyses of mRNA- and microRNA-sequencing data from HGSOC patients of The Cancer Genome Atlas identified 21 microRNAs associated with angiogenesis and 196 mRNAs enriched for adaptive immunity and translation. Coexpression network analysis identified three microRNA networks associated with chemotherapy response enriched for lipoprotein transport and oncogenic pathways, as well as two mRNA networks enriched for ubiquitination and lipid metabolism. These network modules were replicated in two independent ovarian cancer cohorts. Moreover, integrative analyses of the mRNA/microRNA sequencing and single-nucleotide polymorphisms (SNPs) revealed potential regulation of significant mRNA transcripts by microRNAs and SNPs (expression quantitative trait loci). Thus, we report novel transcriptional networks and biological pathways associated with resistance to platinum-based chemotherapy in HGSOC patients. These results expand our understanding of the effector networks and regulators of chemotherapy response, which will help to improve the management of ovarian cancer.

Clinical Significance of Ventricular Premature Contraction Provoked by the Treadmill Test.

Background and Objectives: The treadmill test (TMT) is a predictive tool for myocardial ischemia. Recently, exercise-provoked ventricular premature contracture (VPC) during TMT was shown to have a relation with coronary artery disease and cardiovascular mortality. Therefore, we evaluate clinical correlates of exercise-provoked VPC and compare the predictive power for myocardial ischemia and cardiovascular events. Method: Data of 408 patients (≥18 years of age) who underwent TMT for work up of angina, palpitation, dyspnea, syncope, or arrhythmia between February 2015, and January 2016, were collected with consent at Samsung Medical Center, Seoul, Republic of Korea. Among total of 408 patients, 208 were excluded according to the previous history of PCI or CABG, previous MI, decreased left ventricular ejection fraction lower than 50%, arrhythmia that could affect ST-segment change on ECG. Results: Among 200 patients, 32 (16.0%) developed exercise-provoked VPC (21 patients in the exercise phase, 20 patients in the recovery phase). Of them, 20 patients (10.0%) showed positive TMT, and 4 patients (2.0%) underwent revascularization after TMT. Among 21 patients showing exercise phase VPC, 5 (23.8%) showed positive TMT results. In patients younger than 65 years, exercise phase VPC was associated with positive TMT (odds ratio 6.879, 1.458-32.453) considering demographics and previous medical history in multivariable analysis. Among the 20 patients showing recovery phase VPC, 2 (10.0%) underwent revascularization after TMT. In multivariable analysis, recovery phase VPC was associated with revascularization (odds ratio 9.381, 1.144-76.948) considering age, sex, BMI, and TMT result. Conclusion: VPC during the treadmill test was a useful predictor of myocardial ischemia in this study.

Mass Fabrication of 3D Silicon Nano-/Microstructures by Fab-Free Process Using Tip-Based Lithography.

Methods for the mass fabrication of 3D silicon (Si) microstructures with a 100 nm resolution are developed using scanning probe lithography (SPL) combined with metal-assisted chemical etching (MACE). Protruding Si structures, including Si nanowires of over 10 µm in length and atypical shaped Si nano- and micropillars, are obtained via the MACE of a patterned gold film (negative tone) on Si substrates by dip-pen nanolithography (DPN) with polymer or by nanoshaving alkanethiol self-assembled monolayers (SAMs). Furthermore, recessed Si structures with arbitrary patterning and channels less than 160 nm wide and hundreds of nanometers in depth are obtained via the MACE of a patterned gold film (positive tone) on Si substrates by alkanethiol DPN. As an example of applications using protruded Si structures, nanoimprinting in an area of up to a centimeter is demonstrated through 1D and 2D SPL combined with MACE. Similarly, submicrometer polydimethylsiloxane (PDMS) stamps are employed over millimeter-scale areas for applications using recessed Si structures. In particular, the mass production of arbitrarily shaped Si microparticles at submicrometer resolution is developed using silicon-on-insulator substrates, as demonstrated using optical microresonators, surface-enhanced Raman scattering templates, and smart microparticles for fluorescence signal coding.

First Results from an Axion Haloscope at CAPP around 10.7 µeV.

The Center for Axion and Precision Physics Research at the Institute for Basic Science is searching for axion dark matter using ultralow temperature microwave resonators. We report the exclusion of the axion mass range 10.7126-10.7186 µeV with near Kim-Shifman-Vainshtein-Zakharov (KSVZ) coupling sensitivity and the range 10.16-11.37 µeV with about 9 times larger coupling at 90% confidence level. This is the first axion search result in these ranges. It is also the first with a resonator physical temperature of less than 40 mK.

Electrocardiographic predictors of early recurrence of atrial fibrillation.

BACKGROUND: Electrical cardioversion (ECV) is an effective method for restoring sinus rhythm after atrial fibrillation (AF). However, early recurrence of AF occurs in a significant number of patients after ECV. This study aimed to identify electrocardiographic (ECG) predictors of early AF recurrence after ECV. METHODS: A total of 272 patients with persistent AF undergoing successful ECV were consecutively enrolled in this study. We investigated clinical, echocardiographic, and ECG data. The 12-lead ECG parameters were measured during sinus rhythm right after ECV using a digital caliper. The early AF recurrence was defined as recurrence within 2 months. RESULTS: Of the 272 patients, 165 patients (60.7%) experienced an early AF recurrence. Maximum P-wave duration (PWD) in limb leads (OR: 1.086; 95% CI: 1.019-1.157; p = .012) and P-terminal force (PTF) in V1 (OR: 1.019; 95% CI: 1.004-1.033; p = .011) were independent predictors of early AF recurrence after ECV. The optimal cutoff value of the maximum PWD in limb leads for predicting early AF recurrence was 134 ms, characterized by 90.3% sensitivity and 72.0% specificity. Likewise, the optimal cutoff value of PTF in V1 was 50 ms × mm, characterized by 80.0% sensitivity and 64.5% specificity. CONCLUSION: A longer PWD (>134 ms) and a larger PTF (>50 ms × mm) were useful predictors of early recurrence of AF after successful ECV in clinical practice. A more effective rhythm control therapy such as catheter ablation or rate control strategy rather than a repeat ECV should be considered.

Boosting Visible-Light Photocatalytic Redox Reaction by Charge Separation in SnO2 /ZnSe(N2 H4 )0.5 Heterojunction Nanocatalysts.

In this work, environmentally friendly photocatalysts with attractive catalytic properties are reported that have been prepared by introducing SnO2 quantum dots (QDs) directly onto ZnSe(N2 H4 )0.5 substrates to induce advantageous charge separation. The SnO2 /ZnSe(N2 H4 )0.5 nanocomposites could be easily synthesized through a one-pot hydrothermal process. Owing to the absence of capping ligands, the attached SnO2 QDs displayed superior photocatalytic properties, generating many exposed reactive surfaces. Moreover, the addition of a specified amount of SnO2 boosted the visible-light photocatalytic activity; however, the presence of excess SnO2 QDs in the substrate resulted in aggregation and deteriorated the performance. The spectroscopic data revealed that the SnO2 QDs act as a photocatalytic mediator and enhance the charge separation within the type II band alignment system of the SnO2 /ZnSe(N2 H4 )0.5 heterojunction photocatalysts. The separated charges in the heterojunction nanocomposites promote radical generation and react with pollutants, resulting in enhanced photocatalytic performance.

Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer.

BACKGROUND: A major impediment in the treatment of ovarian cancer is the relapse of chemotherapy-resistant tumors, which occurs in approximately 25% of patients. A better understanding of the biological mechanisms underlying chemotherapy resistance will improve treatment efficacy through genetic testing and novel therapies. METHODS: Using data from high-grade serous ovarian carcinoma (HGSOC) patients in the Cancer Genome Atlas (TCGA), we classified those who remained progression-free for 12 months following platinum-taxane combination chemotherapy as "chemo-sensitive" (N = 160) and those who had recurrence within 6 months as "chemo-resistant" (N = 110). Univariate and multivariate analysis of expression microarray data were used to identify differentially expressed genes and co-expression gene networks associated with chemotherapy response. Moreover, we integrated genomics data to determine expression quantitative trait loci (eQTL). RESULTS: Differential expression of the Valosin-containing protein (VCP) gene and five co-expression gene networks were significantly associated with chemotherapy response in HGSOC. VCP and the most significant co-expression network module contribute to protein processing in the endoplasmic reticulum, which has been implicated in chemotherapy response. Both univariate and multivariate analysis findings were successfully replicated in an independent ovarian cancer cohort. Furthermore, we identified 192 cis-eQTLs associated with the expression of network genes and 4 cis-eQTLs associated with BRCA2 expression. CONCLUSION: This study implicates both known and novel genes as well as biological processes underlying response to platinum-taxane-based chemotherapy among HGSOC patients.

Whole genome sequencing identifies high-impact variants in well-known pharmacogenomic genes.

More than 1100 genetic loci have been correlated with drug response outcomes but disproportionately few have been translated into clinical practice. One explanation for the low rate of clinical implementation is that the majority of associated variants may be in linkage disequilibrium (LD) with the causal variants, which are often elusive. This study aims to identify and characterize likely causal variants within well-established pharmacogenomic genes using next-generation sequencing data from the 1000 Genomes Project. We identified 69,319 genetic variations within 160 pharmacogenomic genes, of which 8207 variants are in strong LD (r2>0.8) with known pharmacogenomic variants. Of the latter, eight are coding or structural variants predicted to have high impact, with 19 additional missense variants that are predicted to have moderate impact. In conclusion, we identified putatively functional variants within known pharmacogenomics loci that could account for the association signals and represent the missing causative variants underlying drug response phenotypes.