Saundersbeck2165

Implementation research often fails to have its intended impact on what programs actually do. Embedding research within target organizational systems represents an effective response to this problem. However, contradictions associated with the approach often prevent its application. We present case studies of the application of embedded implementation research in Bangladesh, Ghana, and Tanzania where initiatives to strengthen community-based health systems were conducted using the embedded science model. In 2 of the cases, implementation research standards that are typically embraced without question were abandoned to ensure pursuit of embedded science. In the third example, statistical rigor was sustained, but this feature of the design was inconsistent with embedded science. In general, rigorous statistical designs employ units of observation that are inconsistent with organizational units that managers can control. Structural contradictions impede host institution ownership of research processes and utilization of results. Moreover, principles of scientific protocol leadership are inconsistent with managerial leadership. These and other embedded implementation science attributes are reviewed together with contradictions that challenged their pursuit in each case. Based on strategies that were effectively applied to offsetting challenges, a process of merging research with management is proposed that is derived from computer science. Known as "agile science," this paradigm combines scientific rigor with management decision making. This agile embedded research approach is designed to sustain scientific rigor while optimizing the integration of learning into managerial decision making.

As HIV testing increases worldwide, programs are reaching individuals without HIV infection who are at risk of exposure and may be candidates for oral pre-exposure prophylaxis (PrEP). Although linkage of individuals with HIV infection to treatment is a global priority (referred to as "test and treat"), less attention is given to individuals with negative HIV test results. We developed the "Test and Prevent" pilot program to intentionally link at-risk clients with negative HIV test results to PrEP services. The intervention included risk assessment of all clients with a negative result from HIV testing (with national risk assessment tool), accompanied referral, fast-tracking, and targeting follow-up.

The intervention was conducted in Bulawayo, Zimbabwe, at 6 public sector sites from October 2019 to February 2020. We collected routine monitoring data from all study sites and tracked referral completion and PrEP initiation among clients who enrolled. We conducted in-depth interviews with providers (n=12), fa were burdened by workload constraints but felt that Test and Prevent was important and should be scaled to other sites.

Intentionally linking clients with negative results to PrEP immediately following HIV testing was found to be acceptable from both provider and client perspectives, yet screening procedures need closer examination and reinforcement for the program to realize a larger impact.

Intentionally linking clients with negative results to PrEP immediately following HIV testing was found to be acceptable from both provider and client perspectives, yet screening procedures need closer examination and reinforcement for the program to realize a larger impact.

Accurate estimation of daily dosage and duration of medication use is essential to pharmacoepidemiological studies using electronic healthcare databases. However, such information is not directly available in many prescription databases, including the Swedish Prescribed Drug Register.

To develop and validate an algorithm for predicting prescribed daily dosage and treatment duration from free-text prescriptions, and apply the algorithm to ADHD medication prescriptions.

We developed an algorithm to predict daily dosage from free-text prescriptions using 8000 ADHD medication prescriptions as the training sample, and estimated treatment periods while taking into account several features including titration, stockpiling and non-perfect adherence. The algorithm was implemented to all ADHD medication prescriptions from the Swedish Prescribed Drug Register in 2013. A validation sample of 1000 ADHD medication prescriptions, independent of the training sample, was used to assess the accuracy for predicted daily dre pharmacoepidemiological studies evaluating utilization, effectiveness, and safety of medication use, which would facilitate evidence-based treatment decision-making.Rearranged during transfection (RET) rearrangements occur in 1% to 2% of lung adenocarcinomas as well as other malignancies and are now established targets for tyrosine kinase inhibitors. We developed three novel RET fusion-positive (RET+) patient-derived cancer cell lines, CUTO22 [kinesin 5B (KIF5B)-RET fusion], CUTO32 (KIF5B-RET fusion), and CUTO42 (echinoderm microtubule-associated protein-like 4-RET fusion), to study RET signaling and response to therapy. We confirmed each of our cell lines expresses the RET fusion protein and assessed their sensitivity to RET inhibitors. We found that the CUTO22 and CUTO42 cell lines were sensitive to multiple RET inhibitors, whereas the CUTO32 cell line was >10-fold more resistant to three RET inhibitors. We discovered that our RET+ cell lines had differential regulation of the mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B (AKT) pathways. After inhibition of RET, the CUTO42 cells had robust inhibition of phosphorylated AKT (pAKT), where) fusion non-small cell lung cancer cell lines and demonstrated that they have differential responses to RET inhibition as well as regulation of downstream signaling, an area that has previously been limited by a lack of diverse cell line modes with endogenous RET fusions. These data offer important insight into regulation of response to RET tyrosine kinase inhibitors and other potential therapeutic targets.Angiotensin II (Ang II) is the most dominant effector component of the renin-angiotensin system (RAS) that generally acts through binding to two main classes of G protein-coupled receptors, namely Ang II subtype 1 receptor (AT1R) and angiotensin II subtype 2 receptor (AT2R). Despite some controversial reports, the activation of AT2R generally antagonizes the effects of Ang II binding on AT1R. Studying AT2R signaling, function, and its specific ligands in cell culture or animal studies has confirmed its beneficial effects throughout the body. These characteristics classify AT2R as part of the protective arm of the RAS that, along with functions of Ang (1-7) through Mas receptor signaling, modulates the harmful effects of Ang II on AT1R in the activated classic arm of the RAS. Although Ang II is the primary ligand for AT2R, we have summarized other natural or synthetic peptide and nonpeptide agonists with critical evaluation of their structure, mechanism of action, and biologic activity. SIGNIFICANCE STATEMENT AT2R is one of the main components of the RAS and has a significant prospective for mediating the beneficial action of the RAS through its protective arm on the body's homeostasis. Targeting AT2R offers substantial clinical application possibilities for modulating various pathological conditions. This review provided concise information regarding the AT2R peptide and nonpeptide agonists and their potential clinical applications for various diseases.Previous short-hairpin RNA knockdown studies have established that depletion of human uracil DNA glycosylase (hUNG) sensitizes some cell lines to 5-fluorodeoxyuridine (FdU). Here, we selectively inhibit the catalytic activity of hUNG by lentiviral transduction of uracil DNA glycosylase inhibitor protein into a large panel of cancer cell lines under control of a doxycycline-inducible promoter. This induced inhibition strategy better assesses the therapeutic potential of small-molecule targeting of hUNG. In total, 6 of 11 colorectal lines showed 6- to 70-fold increases in FdU potency upon hUNG inhibition ("responsive"). This hUNG-dependent response was not observed with fluorouracil (FU), indicating that FU does not operate through the same DNA repair mechanism as FdU in vitro. Potency of the thymidylate synthase inhibitor raltitrexed (RTX), which elevates deoxyuridine triphosphate levels, was only incrementally enhanced upon hUNG inhibition ( less then 40%), suggesting that responsiveness is associated with in human uracil DNA glycosylase. The hUNG-dependent mechanism was present in over 50% of colorectal cell lines tested, suggesting that a significant fraction of human cancers may be sensitized to FdU in the presence of a small-molecule hUNG inhibitor.The draft whole-genome sequences (WGS) of 30 fungal strains isolated from the International Space Station and belonging to the Penicillium and Aspergillus genera were assembled. The WGS will allow for detailed genomic characterization to determine the possible applications and importance for space and biotechnological industries.We report the complete genome sequence of Ensifer mexicanus ITTG R7T, a nitrogen-fixing bacterium isolated from nodules of Acaciella angustissima plants growing naturally in Chiapas, Mexico. FEN1-IN-4 cost The genome is distributed in four replicons comprising one 4.31-Mbp chromosome, one 1,933-Kb chromid, and two plasmids of 436 and 455 Kb.Here, we report the coding-complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate obtained from a nasopharyngeal swab from the first patient with COVID-19 in Gilgit, Pakistan.This paper reports the genome sequences of bacteriophages isolated from soil samples using Microbacterium foliorum Phages Danno and Otwor (cluster EE) have genomes of 17,452 bp and 17,454 bp, respectively, and 25 predicted genes. The phage Scumberland (cluster EC) has a genome of 53,276 bp with 92 predicted genes.Here, we present the complete genome of Bacillus sp. strain IGA-FME-1 (isolated from the bulk soil of maize [Zea mays L.]). This genome consists of 5,147,837 bp, 5,219 protein-coding genes, 112 tRNAs, 13 16S rRNAs, 13 23S rRNAs, and 13 5S rRNAs, with a G+C content of 38.2%.This study describes the genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain detected in the nasopharyngeal swab sample of a coronavirus disease 2019 (COVID-19) patient from the southeastern Khagrachari District of Bangladesh.Data on molecular characterization of coagulase-negative staphylococci causing neonatal sepsis in low-income countries are highly limited. This report highlights the isolation of three Staphylococcus epidermidis non-genome assembly strains (NGASs) from blood samples from neonates with unknown transmission sources. Pathogenic factors and sources of transmission of these strains warrant further investigation.Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae strain 9120005127 was isolated from a wound infection. We describe the draft genome sequence and antibiotic susceptibility of this strain.We report the complete genome sequence of selenate [Se(VI)]-reducing Shigella sonnei SE6-1, which was isolated from stream sediment from an industrial complex in Jeonju, South Korea. The genome sequence is 4,762,774 bp long, with a G+C content of 50.7% and 4,548 genes, including 4,440 coding sequences, 22 rRNA genes, and 86 tRNA genes.