Two of the biggest challenges in medicine today are the need to detect diseases in a noninvasive manner and to differentiate between patients using a single diagnostic tool. The current study targets ...these two challenges by developing a molecularly modified silicon nanowire field effect transistor (SiNW FET) and showing its use in the detection and classification of many disease breathprints (lung cancer, gastric cancer, asthma, and chronic obstructive pulmonary disease). The fabricated SiNW FETs are characterized and optimized based on a training set that correlate their sensitivity and selectivity toward volatile organic compounds (VOCs) linked with the various disease breathprints. The best sensors obtained in the training set are then examined under real-world clinical conditions, using breath samples from 374 subjects. Analysis of the clinical samples show that the optimized SiNW FETs can detect and discriminate between almost all binary comparisons of the diseases under examination with >80% accuracy. Overall, this approach has the potential to support detection of many diseases in a direct harmless way, which can reassure patients and prevent numerous unpleasant investigations.
Persistent inflammatory response has adverse effects on left ventricular (LV) function and remodeling following acute myocardial infarction. We hypothesized that suppression of inflammation with ...interleukin (IL)-10 treatment attenuates LV dysfunction and remodeling after acute myocardial infarction. After the induction of acute myocardial infarction, mice were treated with either saline or recombinant IL-10, and inflammatory response and LV functional and structural remodeling changes were evaluated. IL-10 significantly suppressed infiltration of inflammatory cells and expression of proinflammatory cytokines in the myocardium. These changes were associated with IL-10–mediated inhibition of p38 mitogen-activated protein kinase activation and repression of the cytokine mRNA–stabilizing protein HuR. IL-10 treatment significantly improved LV functions, reduced infarct size, and attenuated infarct wall thinning. Myocardial infarction–induced increase in matrix metalloproteinase (MMP)-9 expression and activity was associated with increased fibrosis, whereas IL-10 treatment reduced both MMP-9 activity and fibrosis. Small interfering RNA knockdown of HuR mimicked IL-10–mediated reduction in MMP-9 expression and activity in NIH3T3 cells. Moreover, IL-10 treatment significantly increased capillary density in the infarcted myocardium which was associated with enhanced STAT3 phosphorylation. Taken together, our studies demonstrate that IL-10 suppresses inflammatory response and contributes to improved LV function and remodeling by inhibiting fibrosis via suppression of HuR/MMP-9 and by enhancing capillary density through activation of STAT3.
The Sample Analysis at Mars (SAM) investigation of the Mars Science Laboratory (MSL) addresses the chemical and isotopic composition of the atmosphere and volatiles extracted from solid samples. The ...SAM investigation is designed to contribute substantially to the mission goal of quantitatively assessing the habitability of Mars as an essential step in the search for past or present life on Mars. SAM is a 40 kg instrument suite located in the interior of MSL’s Curiosity rover. The SAM instruments are a quadrupole mass spectrometer, a tunable laser spectrometer, and a 6-column gas chromatograph all coupled through solid and gas processing systems to provide complementary information on the same samples. The SAM suite is able to measure a suite of light isotopes and to analyze volatiles directly from the atmosphere or thermally released from solid samples. In addition to measurements of simple inorganic compounds and noble gases SAM will conduct a sensitive search for organic compounds with either thermal or chemical extraction from sieved samples delivered by the sample processing system on the Curiosity rover’s robotic arm.
Social media use is pervasive among young adults, and different sites have different purposes, features, and audiences. This study identified classes of young adults based on what combination of ...sites they use and how frequently, and compared their health risk factors and behaviors.
Latent profile models were developed based on frequency of using 10 sites from a national sample of young adults aged 18–24 years (n = 1,062). Bivariate analyses and multivariable regressions examined the relationship between class membership and alcohol, tobacco, and other drug (ATOD) use, and symptoms of depression and anxiety.
The optimal model identified five classes: Low Users (7.9%), High Users (63.1%), Professional Users – high use of LinkedIn (10.1%), Creative Users – high use of Vine and Tumblr (11.5%), and Mainstream Users – high use of Facebook and YouTube (7.4%). Classes differed significantly on ATOD use and depressive symptoms. Compared to High Users, Creative Users had higher odds of using most substances and lower odds of depressive symptoms, Mainstream Users had higher odds of substances used socially (alcohol and hookah), Professional Users had higher odds of using alcohol, cigarettes, and cigars, and Low Users had higher odds of using other drugs (e.g., cocaine and heroin).
A young adult's social media site use profile is associated with ATOD use and depressive symptoms. Use and co-use of certain sites may influence the volume and nature of ATOD-related content and norms young adults experience in social media. Targeting interventions to sites selected based on use patterns associated with each health risk may be effective.
The purpose of this analysis is to evaluate the effect of institutional accrual volume on clinical outcomes among patients receiving chemoradiation for locally advanced non-small cell lung cancer ...(LA-NSCLC) on a phase III trial.
Patients with LA-NSCLC were randomly assigned to 60 Gy or 74 Gy radiotherapy (RT) with concurrent carboplatin/paclitaxel +/- cetuximab on NRG Oncology RTOG 0617. Participating institutions were categorized as low-volume centers (LVCs) or high-volume centers (HVCs) according to the number of patients accrued (≤3 vs > 3). All statistical tests were two-sided.
Range of accrual for LVCs (n = 195) vs HVCs (n = 300) was 1 to 3 vs 4 to 18 patients. Baseline characteristics were similar between the two cohorts. Treatment at a HVC was associated with statistically significantly longer overall survival (OS) and progression-free survival (PFS) compared with treatment at a LVC (median OS = 26.2 vs 19.8 months; HR = 0.70, 95% CI = 0.56 to 0.88, P = .002; median PFS: 11.4 vs 9.7 months, HR = 0.80, 95% CI = 0.65-0.99, P = .04). Patients treated at HVCs were more often treated with intensity-modulated RT (54.0% vs 39.5%, P = .002), had a lower esophageal dose (mean = 26.1 vs 28.0 Gy, P = .03), and had a lower heart dose (median = V5 Gy 38.2% vs 54.1%, P = .006; V50 Gy 3.6% vs 7.3%, P < .001). Grade 5 adverse events (AEs) (5.3% vs 9.2%, P = .09) and RT termination because of AEs (1.3% vs 4.1%, P = .07) were less common among patients treated at HVCs. HVC remained independently associated with longer OS (P = .03) when accounting for other factors.
Treatment at institutions with higher clinical trial accrual volume is associated with longer OS among patients with LA-NSCLC participating in a phase III trial.
In this prospective National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake ...value (SUV) on post-treatment (18)Ffluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non-small-cell lung cancer (NSCLC).
Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models.
Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak.
Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.
Background and Aims Multitarget stool DNA (MT-sDNA) testing is now approved by the U.S. Food and Drug Administration for average-risk colorectal cancer screening. Trials leading to its approval used ...blinded colonoscopy as the reference standard. In the postapproval screen setting, the clinical performance and impact of MT-sDNA testing on unblinded colonoscopy has not been described. We measured the impact that knowledge of a positive MT-sDNA test result has on colonoscopy yield and quality. Methods The unblinded group comprised all patients with positive MT-sDNA results on screening from September 1, 2014 to September 30, 2015 at a single tertiary center. Off-label test patients were excluded. The blinded group included all MT-sDNA–positive participants in a preapproval screening study from the same center. Detailed colonoscopy findings and withdrawal times were recorded. Results There were 172 MT-sDNA–positive patients in the unblinded group and 72 in the blinded group. More total adenomatous/sessile serrated polyps (70% vs 53%, P = .013) and advanced neoplasms (28% vs 21%, P = .27) were detected in unblinded than in blinded groups. Median numbers of polyps detected were 2 (IQR, 1-4) and 1 (IQR, 0-2) in unblinded and blinded groups, respectively ( P = .0007). Among polyps detected, flat or slightly raised lesions in the right side of the colon were proportionately more frequent with unblinded (40%) than with blinded examinations (9%) ( P = .0017). Median withdrawal time was 19 minutes (IQR, 13-29) in the unblinded group compared with 13 minutes (IQR, 10-20) in the blinded group ( P = .0001). Conclusions Knowledge of a positive MT-sDNA result appears to have a beneficial impact on the diagnostic yield and quality of subsequent colonoscopy.
Minimally invasive methods have been described to detect Barrett's esophagus (BE), but are limited by subjectivity and suboptimal accuracy. We identified methylated DNA markers (MDMs) for BE in ...tissue and assessed their accuracy on whole esophagus brushings and capsule sponge samples.
Step 1: Unbiased whole methylome sequencing was performed on DNA from BE and normal squamous esophagus (SE) tissue. Discriminant MDM candidates were validated on an independent patient cohort (62 BE cases, 30 controls) by quantitative methylation specific PCR (qMSP). Step 2: Selected MDMs were further evaluated on whole esophageal brushings (49 BE cases, 36 controls). 35 previously sequenced esophageal adenocarcinoma (EAC) MDMs were also evaluated. Step 3: 20 BE cases and 20 controls were randomized to swallow capsules sponges (25 mm, 10 pores or 20 pores per inch (ppi)) followed endoscopy. DNA yield, tolerability, and mucosal injury were compared. Best MDM assays were performed on this cohort.
Step 1: 19 MDMs with areas under the ROC curve (AUCs) >0.85 were carried forward. Step 2: On whole esophageal brushings, 80% of individual MDM candidates showed high accuracy for BE (AUCs 0.84-0.94). Step 3: The capsule sponge was swallowed and withdrawn in 98% of subjects. Tolerability was superior with the 10 ppi sponge with minimal mucosal injury and abundant DNA yield. A 2-marker panel (VAV3 + ZNF682) yielded excellent BE discrimination (AUC = 1).
Identified MDMs discriminate BE with high accuracy. BE detection appears safe and feasible with a capsule sponge. Corroboration in larger studies is warranted. ClinicalTrials.gov number NCT02560623.
Nonendoscopic Barrett's esophagus (BE) screening may help improve esophageal adenocarcinoma outcomes. We previously demonstrated promising accuracy of methylated DNA markers (MDMs) for the ...nonendoscopic diagnosis of BE using samples obtained from a capsule sponge-on-string (SOS) device. We aimed to assess the accuracy of these MDMs in an independent cohort using a commercial grade assay.
BE cases had ≥ 1 cm of circumferential BE with intestinal metaplasia; controls had no endoscopic evidence of BE. The SOS device was withdrawn 8 minutes after swallowing, followed by endoscopy (the criterion standard). Highest performing MDMs from a previous study were blindly assessed on extracted bisulfite-converted DNA by target enrichment long-probe quantitative amplified signal (TELQAS) assays. Optimal MDM combinations were selected and analyzed using random forest modeling with in silico cross-validation.
Of 295 patients consented, 268 (91%) swallowed the SOS device; 112 cases and 89 controls met the pre-established inclusion criteria. The median BE length was 6 cm (interquartile range 4-9), and 50% had no dysplasia. The cross-validated sensitivity and specificity of a 5 MDM random forest model were 92% (95% confidence interval 85%-96%) and 94% (95% confidence interval 87%-98%), respectively. Model performance was not affected by age, gender, or smoking history but was influenced by the BE segment length. SOS administration was well tolerated (median interquartile range tolerability 2 0, 4 on 10 scale grading), and 95% preferred SOS over endoscopy.
Using a minimally invasive molecular approach, MDMs assayed from SOS samples show promise as a safe and accurate nonendoscopic test for BE prediction.
Young adults are influenced by cigarette package marketing. Pictorial warning labels are a recommended intervention. Evidence demonstrates pictorial warnings impact negative emotion, risk ...perceptions, and motivation to quit smoking, but there is limited research on their effects over time. This study analyzes data from a randomized trial of young adult smokers (N = 229) exposed to a pictorial or text-only cigarette warning. We assessed changes in fear, anger, risk perceptions, and motivation to quit smoking after 4 weeks using latent change score modeling and over 3 months using latent growth modeling. Latent change results showed exposure was associated with increases in fear, anger, and motivation to quit after 4 weeks. Latent growth showed exposure was associated with increases in motivation to quit smoking over 3 months, but not other outcomes. Findings suggest pictorial warning labels produce an emotional response and increase motivation to quit among young adult smokers.
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