Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1.

Introduction: Matching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CGP) can simultaneously assess NSCLC tumors for hundreds of genomic biomarkers and markers for immunotherapy response, leading to quicker and more precise matches to therapeutics.

Methods: In this study, we performed CGP on 7,606 patients with advanced or metastatic NSCLC using the Illumina TruSight Oncology 500 (TSO 500) CGP assay to show its coverage and utility in detecting known and novel features of NSCLC.

Influencing Best Practices for Genomic and Germline Testing in Urology.

Introduction: We evaluated germline and somatic testing practices and compared results from tissue and liquid biopsy specimens in a large community urology setting.

Methods: A retrospective analysis was performed on advanced prostate cancer patients from a single community practice between June 2016 and September 2021. Clinical data and sequencing results from tissue and liquid biopsy specimens were available for 389 patients.

Serial Profiling of Circulating Tumor DNA Identifies Dynamic Evolution of Clinically Actionable Genomic Alterations in High-Risk Neuroblastoma.

Unlabelled: Neuroblastoma evolution, heterogeneity, and resistance remain inadequately defined, suggesting a role for circulating tumor DNA (ctDNA) sequencing. To define the utility of ctDNA profiling in neuroblastoma, 167 blood samples from 48 high-risk patients were evaluated for ctDNA using comprehensive genomic profiling. At least one pathogenic genomic alteration was identified in 56% of samples and 73% of evaluable patients, including clinically actionable ALK and RAS-MAPK pathway variants.

Comparative Effectiveness of Immune Checkpoint Inhibitors vs Chemotherapy by Tumor Mutational Burden in Metastatic Castration-Resistant Prostate Cancer.

Importance: The most useful biomarkers for clinical decision-making identify patients likely to have improved outcomes with one treatment vs another.

Objective: To evaluate treatment class-specific outcomes of patients receiving immune checkpoint inhibitor (ICI) vs taxane chemotherapy by tumor mutational burden (TMB).

Design, Setting, And Participants: This comparative effectiveness analysis of clinical variables and outcomes used prospectively defined biomarker-stratified genomic data from a deidentified clinicogenomic database.

Clinical Utility of Liquid Biopsy to Identify Genomic Heterogeneity and Secondary Cancer Diagnoses: A Case Report.

Liquid biopsy is a valuable tool in advanced and metastatic cancers for detection of genomic alterations in tumors that facilitate personalized targeted therapy approaches. Analyzing circulating tumor DNA (ctDNA) using next-generation sequencing (NGS) provides an opportunity to detect tumor genomic changes during therapy and capture inter- and intra-heterogeneity of genomically divergent cancer cell evolution. Herein, we present a patient with metastatic castration-resistant prostate cancer, with progression to soft tissues, bone, and regional lymph nodes, who was treated with abiraterone plus prednisone, with excellent prostate-specific antigen response.

Clinical and pathological features associated with circulating tumor DNA content in real-world patients with metastatic prostate cancer.

Background: Liquid biopsy is a powerful tool that can enable treatment decisions for metastatic prostate cancer patients with difficult-to-biopsy tumors. However, the detection of genomic alterations via liquid biopsy is limited by the fraction (tumor fraction [TF]) of circulating tumor DNA (ctDNA) within the total cell-free DNA content. While prior work has preliminarily correlated TF with clinical features of prostate cancer, we sought to validate and provide additional resolution, such that a clinical practitioner might anticipate the probability of successful liquid biopsy profiling leveraging commonly assessed clinical and laboratory features.

Partial treatment response to capmatinib in -amplified metastatic intrahepatic cholangiocarcinoma: case report & review of literature.

Cholangiocarcinoma is a highly morbid gastrointestinal malignancy for which available therapies are limited. Standard of care includes cytotoxic chemotherapies such as gemcitabine, platinum agents, nab-paclitaxel, and fluoropyrimidine analogues. However, tolerability of these regimens varies, and patients who do not tolerate chemotherapy have limited targeted therapies and immunotherapy options.

How Is Rheology Involved in 3D Printing of Phase-Separated PVC-Acrylate Copolymers Obtained by Free Radical Polymerization.

New auto-plasticised copolymers of poly(vinyl chloride)-r-(acrylate) and polyvinylchloride, obtained by radical polymerization, are investigated to analyse their capacity to be processed by 3D printing. The specific microstructure of the copolymers gives rise to a phase-separated morphology constituted by poly(vinyl chloride) (PVC) domains dispersed in a continuous phase of acrylate-vinyl chloride copolymer. The analysis of the rheological results allows the suitability of these copolymers to be assessed for use in a screw-driven 3D printer, but not by the fused filament fabrication method.

Young-Onset Colon Cancer and Recurrence Risk by Gene Expression.

The incidence and mortality from colorectal cancer in younger adults (younger than 55 years) is increasing. We reviewed the complete database of a gene-expression test, Oncotype DX Colon Recurrence Score test, to determine age-related differences in recurrence score (RS) and single-gene results (7 cancer-related of the 12-gene assay). We included 20 478 stage II and III A and B colon cancer patients submitted to Genomic Health.

Searching for Rheological Conditions for FFF 3D Printing with PVC Based Flexible Compounds.

Rheology is proposed as a tool to explore plasticized poly(vinyl chloride) (PVC) formulations to be used in the fused filament fabrication (FFF) 3D printing process and so manufactures flexible and ductile objects by this technique. The viscoelastic origin of success/failure in FFF of these materials is investigated. The analysis of buckling of the filament is based on the ratio between compression modulus and viscosity, but for a correct approach the viscosity should be obtained under the conditions established in the nozzle.

Correction to: Lymph Node Status in Breast Cancer Does Not Predict Tumor Biology.

In the "Results" section third paragraph, second sentence, there is an error. The corrected sentence is as follows.

Lymph Node Status in Breast Cancer Does Not Predict Tumor Biology.

Background/objective: The 21-gene Oncotype DX Breast Recurrence Score (RS) assay has been prospectively validated as prognostic and predictive in node-negative, estrogen receptor-positive (ER+)/HER2- breast cancer patients. Less is known about its prognostic role in node-positive breast cancer. We compared RS results among patients with lymph node-negative (N0), micrometastatic (N1mi), and macrometastatic (N+) breast cancer to determine if nodal metastases are associated with more aggressive biology, as determined by RS.

Epigenetic Homogeneity Within Colorectal Tumors Predicts Shorter Relapse-Free and Overall Survival Times for Patients With Locoregional Cancer.

Background & Aims: There are few validated biomarkers that can be used to predict outcomes for patients with colorectal cancer. Part of the challenge is the genetic and molecular heterogeneity of colorectal tumors not only among patients, but also within tumors. We have explored intratumor heterogeneity at the epigenetic level, due to its dynamic nature.

Monopersulfate photocatalysis under 365 nm radiation. Direct oxidation and monopersulfate promoted photocatalysis of the herbicide tembotrione.

Oxone(®) (potassium monopersulfate, MPS) has been used to oxidize the herbicide tembotrione in aqueous solution. Tembotrione elimination kinetics by MPS direct oxidation has been studied. The influence of the main operating variables affecting the process (MPS concentration, temperature and pH) has been evaluated.

Safety and efficacy of neratinib in combination with weekly paclitaxel and trastuzumab in women with metastatic HER2‑positive breast cancer: an NSABP Foundation Research Program phase I study.

Purpose: Neratinib is an oral, small-molecule inhibitor that irreversibly binds to pan-HER (ErbB) receptor tyrosine kinases. Studies suggest that dual anti-HER therapies utilized in breast cancer patients are more efficacious than single agents in both the metastatic and neoadjuvant settings. In this phase I study, neratinib was combined with trastuzumab and paclitaxel in metastatic HER2-positive patients.

The effectiveness of a health promotion with group intervention by clinical trial. Study protocol.

Background: The promotion of health and the interventions in community health continue to be one of the pending subjects of our health system. The most prevalent health problems (cardiovascular diseases, cancer, diabetes..

Cdc25B dual-specificity phosphatase inhibitors identified in a high-throughput screen of the NIH compound library.

The University of Pittsburgh Molecular Library Screening Center (Pittsburgh, PA) conducted a screen with the National Institutes of Health compound library for inhibitors of in vitro cell division cycle 25 protein (Cdc25) B activity during the pilot phase of the Molecular Library Screening Center Network. Seventy-nine (0.12%) of the 65,239 compounds screened at 10 muM met the active criterion of > or =50% inhibition of Cdc25B activity, and 25 (31.

Microtubule binding and disruption and induction of premature senescence by disorazole C(1).

Disorazoles comprise a family of 29 macrocyclic polyketides isolated from the fermentation broth of the myxobacterium Sorangium cellulosum. The major fermentation product, disorazole A(1), was found previously to irreversibly bind to tubulin and to have potent cytotoxic activity against tumor cells, possibly because of its highly electrophilic epoxide moiety. To test this hypothesis, we synthesized the epoxide-free disorazole C(1) and found it retained potent antiproliferative activity against tumor cells, causing prominent G(2)/M phase arrest and inhibition of in vitro tubulin polymerization.

The 2,4-D herbicide effects on acetylcholinesterase activity and metabolic parameters of piava freshwater fish (Leporinus obtusidens).

The effects of 2,4-D (1 or 10 mg/L) on acetylcholinesterase (AChE) and metabolic parameters were evaluated in piava (Leporinus obtusidens) after 96 h. AChE activity was significantly reduced in the brain at a concentration of 10 mg/L and in the muscle at both concentrations tested. Muscle glycogen and lactate were significantly reduced for both 2,4-D concentrations but no significant change was observed in liver glycogen.

Development and optimization of high-throughput in vitro protein phosphatase screening assays.

We describe here detailed protocols to design, optimize and validate in vitro phosphatase assays that we have utilized to conduct high-throughput screens for inhibitors of dual-specificity phosphatases: CDC25B, mitogen-activated protein kinase phosphatase (MKP)-1 and MKP-3. We provide details of the critical steps that are needed to effectively miniaturize the assay into a 384-well, high-throughput format that is both reproducible and cost effective. In vitro phosphatase assays that are optimized according to these protocols should satisfy the assay performance criteria required for a robust high-throughput assay with Z-factors >0.

Responding to the socially motivated behaviors of early adolescents: recommendations for classroom management.

Much of the literature on middle school teaching focuses upon the developmental stresses early adolescents typically experience. Yet the literature rarely offers teachers specific ways to respond to student behaviors which result from these developmental changes. This paper delineates the physical, cognitive, and social-emotional motivations behind typical early adolescent behaviors, and then offers middle school educators classroom-management approaches for responding to these student behaviors.

14-Fluorobacteriorhodopsin and other fluorinated and 14-substituted analogues. An extra, unusually red-shifted pigment formed during dark adaptation.

Five vinyl-substituted fluororetinal analogues (8-F, 10-F, 12-F, 14-F, and 13,14-F2) were found to give bacteriorhodopsin analogues with properties similar to those of the parent system. Of these, only 14-fluororetinal was found to give an extra red-shifted BR analogue (lambda max less than or equal to 680 nm) in equilibrium with the normal 587-nm pigment. The 680-nm pigment was enriched upon irradiation.

[Biochemistry of the cyclic evolution of Triatoma infestans (Vinchuca). IV. De novo biosynthesis of lipids in fat body and testicles].

The de novo biosynthesis of lipids by isolated fat bodies and testicles of Triatoma infestans was demonstrated by incubation with 1 14C sodium acetate. The fat body synthetized preferentially triacylglycerols but the label was also found in phospholipids. When hemolymph was added to the medium the label found in diacylglycerols was largely increased.

[Biochemistry of the cyclic evolution of Triatoma infestans (Vinchuca). III. Dynamics of the incorporation of fatty acids in lipids].

More than 80% of total lipids of Triatoma infestans are triacylglycerols and only 3.7% and 4.0% are phosphatidyl-ethanolamine and phosphatidylcholine, whereas the diacylglycerols are 0.

[Biochemistry of the developmental cycle of Triatoma infestans (Vinchuca). 2. Biosynthesis of fatty acids].

The biosynthesis of fatty acids in Triatoma infestans was studied in all the nymph stages and adult insects by feeding experiments with 1-14C acetate. In other experiments labeled acetate, 1-14C palmitate or 1-14C stearate were injected in the abdomen. In another group of experiments the abdominal non intestinal tissue of adult insects was homogenized and the supernatants of 10 000 X g and 105 000 X g were incubated with 1-14C acetyl-CoA.