Terryhagen6057

Immunotherapy has been associated with improved outcomes among patients who have received previous treatment for microsatellite instability-high (MSI-H) tumors.

To evaluate the antitumor activity of pembrolizumab therapy vs chemotherapy among patients with MSI-H advanced gastric or gastroesophageal junction (G/GEJ) cancer regardless of the line of therapy in which it was received.

This post hoc analysis of the phase 2 KEYNOTE-059 (third-line treatment or higher) single-arm trial and the phase 3 KEYNOTE-061 (second-line treatment) and KEYNOTE-062 (first-line treatment) randomized trials included patients with advanced G/GEJ cancer from 52 sites in 16 countries enrolled in KEYNOTE-059, 148 sites in 30 countries enrolled in KEYNOTE-061, and 200 sites in 29 countries enrolled in KEYNOTE-062. Patients were enrolled from March 2, 2015, to March 26, 2016, in KEYNOTE-059; from June 4, 2015, to July 26, 2016, in KEYNOTE-061; and from September 18, 2015, to May 26, 2017, in KEYNOTE-062, with data cutoff dates of to NR) in KEYNOTE-061 (vs 3.5 months [95% CI, 2.0-9.8 months] for chemotherapy). In KEYNOTE-062, the median PFS was 11.2 months (95% CI, 1.5 months to NR) for pembrolizumab, NR (95% CI, 3.6 months to NR) for pembrolizumab plus chemotherapy, and 6.6 months (95% CI, 4.4-8.3 months) for chemotherapy. The objective response rate (ORR) for pembrolizumab was 57.1% in KEYNOTE-059 and 46.7% (vs 16.7% for chemotherapy) in KEYNOTE-061. In KEYNOTE-062, the ORR was 57.1% for pembrolizumab , 64.7% for pembrolizumab plus chemotherapy, and 36.8% for chemotherapy.

Findings from this study indicate that MSI-H status may be a biomarker for pembrolizumab therapy among patients with advanced G/GEJ cancer regardless of the line of therapy in which it was received.

ClinicalTrials.gov Identifiers NCT02335411, NCT02370498, and NCT02494583.

ClinicalTrials.gov Identifiers NCT02335411, NCT02370498, and NCT02494583.

Adenoviral conjunctivitis is highly contagious, can be associated with systemic infections, and can cause chronic visual impairment. It accounts for a large proportion of acute conjunctivitis. Outbreaks of epidemic keratoconjunctivitis (EKC) are costly in terms of productivity loss from work furloughs and spread to patients and have resulted in clinic and departmental closures.

To examine the institutional cost savings of a policy to diagnose adenoviral conjunctivitis and triage and furlough medical center employees with this condition to prevent outbreaks.

This quality improvement study assessed Johns Hopkins Medicine employees with red eye from November 1, 2011, through October 31, 2018, who were triaged at the occupational health clinic whose conditions were diagnosed using polymerase chain reaction (PCR) validated for adenoviral conjunctivitis.

Only employees with positive PCR test results were furloughed, with furlough length tailored to subtype (a minimum of 2 weeks for EKC and 1 week otherwise)y other institutions and for development of a rapid, sensitive, and specific diagnostic test for adenoviral conjunctivitis.

In this quality improvement study, this policy, notable for development and use of PCR for adenoviral conjunctivitis on a large scale, resulted in substantial cost savings from fewer work furloughs compared with the number of employees who would have been furloughed based on clinical diagnosis. These results may provide impetus for policy adoption by other institutions and for development of a rapid, sensitive, and specific diagnostic test for adenoviral conjunctivitis.Increasing evidence suggests that n-hexane induces nerve injury via neuronal apoptosis induced by its active metabolite 2,5-hexanedione (HD). However, the underlying mechanism remains unknown. Studies have confirmed that pro-nerve growth factor (proNGF), a precursor of mature nerve growth factor (mNGF), might activate apoptotic signaling by binding to p75 neurotrophin receptor (p75NTR) in neurons. Therefore, we studied the mechanism of the proNGF/p75NTR pathway in HD-induced neuronal apoptosis. https://www.selleckchem.com/products/gsk2193874.html Sprague-Dawley (SD) rats were injected with 400 mg/kg HD once a day for 5 weeks, and VSC4.1 cells were treated with 10, 20, and 40 mM HD in vitro. Results showed that HD effectively induced neuronal apoptosis. Moreover, it up-regulated proNGF and p75NTR levels, activated c-Jun N-terminal kinase (JNK) and c-Jun, and disrupted the balance between B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Our findings revealed that the proNGF/p75NTR signaling pathway was involved in HD-induced neuronal apoptosis; it can serve as a theoretical basis for further exploration of the neurotoxic mechanisms of HD.

Traditionally, an individual can only query and retrieve information from a genome browser by using accessories such as a mouse and keyboard. However, technology has changed the way that people interact with their screens. We hypothesized that we could leverage technological advances to use voice recognition as an interactive input to query and visualize genomic information.

We developed an Amazon Alexa skill called Gene Tracer that allows users to use their voice to find disease-associated gene information, deleterious mutations, and gene networks, while simultaneously enjoy a genome browser-like visualization experience on their screen. As the voice can be well recognized and understood, Gene Tracer provides users with more flexibility to acquire knowledge and is broadly applicable to other scenarios.

Alexa skill store (https//www.amazon.com/LT-Gene-tracer/dp/B08HCL1V68/) and a demonstration video (https//youtu.be/XbDbx7JDKmI).

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

Microbial gene catalogs are data structures that organize genes found in microbial communities, providing a reference for standardized analysis of the microbes across samples and studies. Although gene catalogs are commonly used, they have not been critically evaluated for their effectiveness as a basis for metagenomic analyses.

As a case study, we investigate one such catalog, the Integrated Gene Catalog (IGC), however our observations apply broadly to most gene catalogs constructed to date. We focus on both the approach used to construct this catalog and, on its effectiveness, when used as a reference for microbiome studies. Our results highlight important limitations of the approach used to construct the IGC and call into question the broad usefulness of gene catalogs more generally. We also recommend best practices for the construction and use of gene catalogs in microbiome studies and highlight opportunities for future research.

All supporting scripts for our analyses can be found on GitHub https//github.