Objectives We tested whether an assessment of myocardial scarring by cardiac magnetic resonance imaging (MRI) would improve risk stratification in patients evaluated for implantable ...cardioverter-defibrillator (ICD) implantation. Background Current sudden cardiac death risk stratification emphasizes left ventricular ejection fraction (LVEF); however, most patients suffering sudden cardiac death have a preserved LVEF, and many with poor LVEF do not benefit from ICD prophylaxis. Methods One hundred thirty-seven patients undergoing evaluation for possible ICD placement were prospectively enrolled and underwent cardiac MRI assessment of LVEF and scar. The pre-specified primary endpoint was death or appropriate ICD discharge for sustained ventricular tachyarrhythmia. Results During a median follow-up of 24 months the primary endpoint occurred in 39 patients. Whereas the rate of adverse events steadily increased with decreasing LVEF, a sharp step-up was observed for scar size >5% of left ventricular mass (hazard ratio HR: 5.2; 95% confidence interval CI: 2.0 to 13.3). On multivariable Cox proportional hazards analysis, including LVEF and electrophysiological-study results, scar size (as a continuous variable or dichotomized at 5%) was an independent predictor of adverse outcome. Among patients with LVEF >30%, those with significant scarring (>5%) had higher risk than those with minimal or no (≤5%) scarring (HR: 6.3; 95% CI: 1.4 to 28.0). Those with LVEF >30% and significant scarring had risk similar to patients with LVEF ≤30% (p = 0.56). Among patients with LVEF ≤30%, those with significant scarring again had higher risk than those with minimal or no scarring (HR: 3.9; 95% CI: 1.2 to 13.1). Those with LVEF ≤30% and minimal scarring had risk similar to patients with LVEF >30% (p = 0.71). Conclusions Myocardial scarring detected by cardiac MRI is an independent predictor of adverse outcome in patients being considered for ICD placement. In patients with LVEF >30%, significant scarring (>5% LV) identifies a high-risk cohort similar in risk to those with LVEF ≤30%. Conversely, in patients with LVEF ≤30%, minimal or no scarring identifies a low-risk cohort similar to those with LVEF >30%.
Objectives
To determine the effects of cognitive training on cognitive abilities and everyday function over 10 years.
Design
Ten‐year follow‐up of a randomized, controlled single‐blind trial ...(Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE)) with three intervention groups and a no‐contact control group.
Setting
Six U.S. cities.
Participants
A volunteer sample of 2,832 persons (mean baseline age 73.6; 26% African American) living independently.
Intervention
Ten training sessions for memory, reasoning, or speed of processing; four sessions of booster training 11 and 35 months after initial training.
Measurements
Objectively measured cognitive abilities and self‐reported and performance‐based measures of everyday function.
Results
Participants in each intervention group reported less difficulty with instrumental activities of daily living (IADLs) (memory: effect size = 0.48, 99% confidence interval (CI) = 0.12–0.84; reasoning: effect size = 0.38, 99% CI = 0.02–0.74; speed of processing: effect size = 0.36, 99% CI = 0.01–0.72). At a mean age of 82, approximately 60% of trained participants, versus 50% of controls (P < .05), were at or above their baseline level of self‐reported IADL function at 10 years. The reasoning and speed‐of‐processing interventions maintained their effects on their targeted cognitive abilities at 10 years (reasoning: effect size = 0.23, 99% CI = 0.09–0.38; speed of processing: effect size = 0.66, 99% CI = 0.43–0.88). Memory training effects were no longer maintained for memory performance. Booster training produced additional and durable improvement for the reasoning intervention for reasoning performance (effect size = 0.21, 99% CI = 0.01–0.41) and the speed‐of‐processing intervention for speed‐of‐processing performance (effect size = 0.62, 99% CI = 0.31–0.93).
Conclusion
Each Advanced Cognitive Training for Independent and Vital Elderly cognitive intervention resulted in less decline in self‐reported IADL compared with the control group. Reasoning and speed, but not memory, training resulted in improved targeted cognitive abilities for 10 years.
•Biorefinery and bioprocessing are sustainable ways for resource conservation.•Circular bioeconomy significantly reduces food waste accumulation.•In depth studies are necessary to close knowledge ...gaps in field of food waste valorization.•The major stumbling block in resource recovery from food waste is cost of production.
Sustainable development of circular bioeconomy concept is only possible upon adopting potential advanced technologies for food waste valorization. This approach can simultaneously answer resources and environmental challenges incurred due to capital loss and greenhouse gases accumulation. Food waste valorization opens new horizons of economical growth, bringing waste as an opportunity feedstock for bio processes to synthesize biobased products from biological source in a circular loop. Advanced technologies like Ultrasound assisted extraction, Microwave assisted extraction, bioreactors, enzyme immobilization assisted extraction and their combination mitigates the global concern caused due to mismanagement of food waste. Food waste decomposition to sub-zero level using advanced techniques fabricates food waste into bio-based products like bioactive compounds (antioxidants, pigments, polysaccharides, polyphenols, etc.); biofuels (biodiesel, biomethane, biohydrogen); and bioplastics. This review abridges merits and demerits of various advanced techniques extended for food waste valorization and contribution of food waste in revenue generation as value added products.
In this phase I study (BLOOM), osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was evaluated in patients with leptomeningeal metastases (LMs) ...from EGFR-mutated (EGFRm) advanced non-small-cell lung cancer (NSCLC) whose disease had progressed on previous EGFR-TKI therapy.
Patients with cytologically confirmed LM received osimertinib 160 mg once daily. Objectives were to assess confirmed objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), and safety. Additional efficacy evaluations included changes from baseline in CSF cytology and neurologic examination. Measurable lesions were assessed by investigator according to RECIST version 1.1. LMs were assessed by neuroradiologic blinded central independent review (BICR) according to Response Assessment in Neuro-Oncology LM radiologic criteria and by investigator.
Forty-one patients were enrolled. LM ORR and DoR by neuroradiologic BICR were 62% (95% CI, 45% to 78%) and 15.2 months (95% CI, 7.5 to 17.5 months), respectively. Overall, ORR by investigator was 41% (95% CI, 26% to 58%), and median DoR was 8.3 months (95% CI, 5.6 to 16.5 months). Median investigator-assessed PFS was 8.6 months (95% CI, 5.4 to 13.7 months) with 78% maturity; median OS was 11.0 months (95% CI, 8.0 to 18.0 months) with 68% maturity. CSF tumor cell clearance was confirmed in 11 (28%; 95% CI, 15% to 44%) of 40 patients. Neurologic function was improved in 12 (57%) of 21 patients with an abnormal assessment at baseline. The adverse event and PK profiles were consistent with previous reports for osimertinib.
Osimertinib showed meaningful therapeutic efficacy in the CNS and a manageable safety profile at 160 mg once daily in patients with EGFRm NSCLC and LM.
The integration of nanoporous materials such as metal organic frameworks (MOFs) with sensitive transducers can result in robust sensing platforms for monitoring gases and chemical vapors for a range ...of applications. Here, we report on an integration of the zeolitic imidazolate framework - 8 (ZIF-8) MOF with surface acoustic wave (SAW) and thickness shear mode quartz crystal microbalance (QCM) devices to monitor carbon dioxide (CO
2
) and methane (CH
4
) under ambient conditions. The MOF was directly coated on the Y-Z LiNbO
3
SAW delay lines (operating frequency,
f
0
= 436 MHz) and AT-cut quartz TSM resonators (resonant frequency,
f
0
= 9 MHz) and the devices were tested for various gases in N
2
under ambient conditions. The devices were able to detect the changes in CO
2
or CH
4
concentrations with relatively higher sensitivity to CO
2
, which was due to its higher adsorption potential and heavier molecular weight. The sensors showed full reversibility and repeatability which were attributed to the physisorption of the gases into the MOF and high stability of the devices. Both types of sensors showed linear responses relative to changes in the binary gas compositions thereby allowing to construct calibration curves which correlated well with the expected mass changes in the sorbent layer based on mixed-gas gravimetric adsorption isotherms measured on bulk samples. For 200 nm thick films, the SAW sensitivities to CO
2
and CH
4
were 1.44 × 10
−6
/vol% and 8 × 10
−8
/vol%, respectively, against the QCM sensitivities 0.24 × 10
−6
/vol% and 1 × 10
−8
/vol%, respectively, which were evaluated as the fractional change in the signal. The SAW sensors were also evaluated for 100 nm-300 nm thick films, the sensitivities of which were found to increase with the thickness due to the increased number of pores for the adsorption of a larger amount of gases. In addition, the MOF-coated SAW delay lines had a good response in wireless mode, demonstrating their potential to operate remotely for the detection of the gases at emission sites across the energy infrastructure.
The integration of nanoporous materials such as metal organic frameworks (MOFs) with sensitive transducers can result in robust sensing platforms for monitoring gases and chemical vapors for a range of applications.
c-Myc (Myc) is an important transcriptional regulator in embryonic stem (ES) cells, somatic cell reprogramming, and cancer. Here, we identify a Myc-centered regulatory network in ES cells by ...combining protein-protein and protein-DNA interaction studies and show that Myc interacts with the NuA4 complex, a regulator of ES cell identity. In combination with regulatory network information, we define three ES cell modules (Core, Polycomb, and Myc) and show that the modules are functionally separable, illustrating that the overall ES cell transcription program is composed of distinct units. With these modules as an analytical tool, we have reassessed the hypothesis linking an ES cell signature with cancer or cancer stem cells. We find that the Myc module, independent of the Core module, is active in various cancers and predicts cancer outcome. The apparent similarity of cancer and ES cell signatures reflects, in large part, the pervasive nature of Myc regulatory networks.
Display omitted
► Myc associates with NuA4 complex, a critical regulator in ES cell identity ► Three regulatory modules (Core, PrC, and Myc) are defined in ES cells ► Core, PrC, and Myc modules are functionally separable ► Myc module accounts for the similarity of ES cell and cancer signatures
Nanotechnology applications in cancer Nie, Shuming; Xing, Yun; Kim, Gloria J ...
Annual review of biomedical engineering,
01/2007, Letnik:
9, Številka:
1
Journal Article
Recenzirano
Cancer nanotechnology is an interdisciplinary area of research in science, engineering, and medicine with broad applications for molecular imaging, molecular diagnosis, and targeted therapy. The ...basic rationale is that nanometer-sized particles, such as semiconductor quantum dots and iron oxide nanocrystals, have optical, magnetic, or structural properties that are not available from molecules or bulk solids. When linked with tumor targeting ligands such as monoclonal antibodies, peptides, or small molecules, these nanoparticles can be used to target tumor antigens (biomarkers) as well as tumor vasculatures with high affinity and specificity. In the mesoscopic size range of 5-100 nm diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents. Recent advances have led to bioaffinity nanoparticle probes for molecular and cellular imaging, targeted nanoparticle drugs for cancer therapy, and integrated nanodevices for early cancer detection and screening. These developments raise exciting opportunities for personalized oncology in which genetic and protein biomarkers are used to diagnose and treat cancer based on the molecular profiles of individual patients.
The incidence of recurrence after curative resection among patients with stage IB, II, or IIIA non–small-cell lung cancer is high and is only slightly lower with adjuvant chemotherapy. A randomized ...trial of adjuvant osimertinib involving patients with
EGFR
mutation–positive NSCLC showed a substantial decrease in recurrence. Central nervous system relapses were also significantly reduced.
Adjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was ...found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA.
Patients with resected stages IB to IIIA EGFRm NSCLC were randomized 1:1 to receive osimertinib or placebo for 3 years. Adjuvant chemotherapy before randomization was not mandatory, per physician and patient choice. DFS in the overall population (IB–IIIA), with and without adjuvant chemotherapy, was a prespecified analysis. Exploratory analyses included the following: adjuvant chemotherapy use by patient age, disease stage, and geographic location; DFS by adjuvant chemotherapy use and disease stage.
Overall, 410 of 682 patients (60%) received adjuvant chemotherapy (osimertinib, n = 203; placebo, n = 207) for a median duration of 4.0 cycles. Adjuvant chemotherapy use was more frequent in patients: aged less than 70 years (338 of 509; 66%) versus more than or equal to 70 years (72 of 173; 42%); with stages II to IIIA (352 of 466; 76%) versus stage IB (57 of 216; 26%); and enrolled in Asia (268 of 414; 65%) versus outside of Asia (142 of 268; 53%). A DFS benefit favoring osimertinib versus placebo was observed in patients with (DFS hazard ratio = 0.16, 95% confidence interval: 0.10–0.26) and without adjuvant chemotherapy (hazard ratio = 0.23, 95% confidence interval: 0.13–0.40), regardless of disease stage.
These findings support adjuvant osimertinib as an effective treatment for patients with stages IB to IIIA EGFRm NSCLC after resection, with or without previous adjuvant chemotherapy.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium ...of gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)-approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endogenous tumors from a mouse model for human SCLC. The candidate drugs activate stress pathways and induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein-coupled receptors. The candidate drugs inhibit the growth of other neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell carcinoma. These experiments identify novel targeted strategies that can be rapidly evaluated in patients with neuroendocrine tumors through the repurposing of approved drugs.
Our work shows the power of bioinformatics-based drug approaches to rapidly repurpose FDA-approved drugs and identifies a novel class of molecules to treat patients with SCLC, a cancer for which no effective novel systemic treatments have been identified in several decades. In addition, our experiments highlight the importance of novel autocrine mechanisms in promoting the growth of neuroendocrine tumor cells.
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