Reaction times (in ms) of Experiment 3, in which participants were asked to remember digits in Display 1 row by row.

<p>1st, 2nd, and 3rd indicate the order of individual comparisons.</p

Reaction times (in ms) of Experiment 1, in which participants were asked to remember digits in Display 1 column by column, from top to bottom.

<p>1st, 2nd, and 3rd indicate the order of individual comparisons.</p

Examples of experimental trials.

<p>Participants are required to memorize the digits in Display 1 and, when seeing Display 2, respond by comparing the magnitude of digits row-by-row. Depending on the conditions, the to-be-compared columns may come from Display 2 (A), Display 1 and 2 (B), and Display 1 (C).</p

Reaction times (in ms) of Experiment 2, in which participants were asked to remember digits in Display 1 column by column, from bottom to top.

<p>1st, 2nd, and 3rd indicate the order of individual comparisons.</p

Aminopyridyl/Pyrazinyl Spiro[indoline-3,4′-piperidine]-2-ones As Highly Selective and Efficacious c‑Met/ALK Inhibitors

A series of novel aminopyridyl/pyrazinyl-substituted spiro­[indoline-3,4′-piperidine]-2-ones were designed, synthesized, and tested in various in vitro/in vivo pharmacological and antitumor assays. 6-[6-Amino-5-[(1<i>R</i>)-1-(2,6-dichloro-3-fluorophenyl)­ethoxy]-3-pyridyl]-1′-methylspiro­[indoline-3,4′-piperidine]-2-one (compound <b>5b</b> or <b>SMU-B</b>) was identified as a potent, highly selective, well-tolerated, and orally efficacious c-Met/ALK dual inhibitor, which showed pharmacodynamics effect by inhibiting c-Met phosphorylation in vivo and significant tumor growth inhibitions (>50%) in GTL-16 human gastric carcinoma xenograft models

Additional file 1 of The pathogenicity of vancomycin-resistant Enterococcus faecalis to colon cancer cells

Supplementary Material 1

Multiplex Digital Polymerase Chain Reaction on a Droplet Array SlipChip for Analysis of <i>KRAS</i> Mutations in Pancreatic Cancer

Pancreatic cancer is a terminal disease with high mortality and very poor prognosis. A sensitive and quantitative analysis of KRAS mutations in pancreatic cancer provides a tool not only to understand the biological mechanisms of pancreatic cancer but also for diagnosis and treatment monitoring. Digital polymerase chain reaction (PCR) is a promising tool for KRAS mutation analysis, but current methods generally require a complex microfluidic handling system, which can be challenging to implement in routine research and point-of-care clinical diagnostics. Here, we present a droplet-array SlipChip (da-SlipChip) for the multiplex quantification of KRAS G12D, V, R, and C mutant genes with the wild-type (WT) gene background by dual color (FAM/ROX) fluorescence detection. This da-SlipChip is a high-density microwell array of 21,696 wells of 200 pL in 4 by 5424 microwell format with simple loading and slipping operation. It does not require the same precise alignment of microfeatures on the different plates that are acquired by the traditional digital PCR SlipChip. This device can provide accurate quantification of both mutant genes and the WT KRAS gene. We collected tumor tissue, paired normal pancreatic tissue, and other normal tissues from 18 pancreatic cancer patients and analyzed the mutation profiles of KRAS G12D, V, R, and C in these samples; the results from the multiplex digital PCR on da-SlipChip agree well with those of next-generation sequencing (NGS). This da-SlipChip moves digital PCR closer to the practical point-of-care applications not only for detecting KRAS mutations in pancreatic cancer but also for other applications that require precise nucleic acid quantification with high sensitivity

Molecular Simulation Studies on the Binding Selectivity of Type‑I Inhibitors in the Complexes with ROS1 versus ALK

ROS1 and ALK are promising targets of anticancer drugs for non-small-cell lung cancer. Since they have 49% amide acid sequence homology in the kinases domain and 77% identity at the ATP binding area, some ALK inhibitors also showed some significant responses for ROS1 in the clinical trial, such as the type-I binding inhibitor crizotinib and PF-06463922. As a newly therapeutic target, the selective ROS1 inhibitor is relatively rare. Moreover, the molecular basis for the selectivity of ROS1 versus ALK still remains unclear. In order to disclose the binding preference toward ROS1 over ALK and to aid the design of selective ROS1 inhibitors, the specific interactions and difference of conformational changes in the dual and selective ROS1/ALK inhibitors systems were investigated by molecular dynamics (MD) simulation and principle component analysis (PCA) in our work. Afterward, binding free energies (MM/GBSA) and binding free energies decomposition analysis indicated that the dominating effect of Van der Waals interaction drives the specific binding process of the type-I inhibitor, and residues of the P-loop and the DFG motif would play an important role in selectivity. On the basis of the modeling results, the new designed compound <b>14c</b> was verified as a selective ROS1 inhibitor versus ALK, and SMU-B was a dual ROS1/ALK inhibitor by the kinase inhibitory study. These results are expected to facilitate the discovery and rational design of novel and specific ROS1 inhibitors

Factors Affecting Accuracy of Data Abstracted from Medical Records

<div><p>Objective</p><p>Medical record abstraction (MRA) is often cited as a significant source of error in research data, yet MRA methodology has rarely been the subject of investigation. Lack of a common framework has hindered application of the extant literature in practice, and, until now, there were no evidence-based guidelines for ensuring data quality in MRA. We aimed to identify the factors affecting the accuracy of data abstracted from medical records and to generate a framework for data quality assurance and control in MRA.</p><p>Methods</p><p>Candidate factors were identified from published reports of MRA. Content validity of the top candidate factors was assessed via a four-round two-group Delphi process with expert abstractors with experience in clinical research, registries, and quality improvement. The resulting coded factors were categorized into a control theory-based framework of MRA. Coverage of the framework was evaluated using the recent published literature.</p><p>Results</p><p>Analysis of the identified articles yielded 292 unique factors that affect the accuracy of abstracted data. Delphi processes overall refuted three of the top factors identified from the literature based on importance and five based on reliability (six total factors refuted). Four new factors were identified by the Delphi. The generated framework demonstrated comprehensive coverage. Significant underreporting of MRA methodology in recent studies was discovered.</p><p>Conclusion</p><p>The framework generated from this research provides a guide for planning data quality assurance and control for studies using MRA. The large number and variability of factors indicate that while prospective quality assurance likely increases the accuracy of abstracted data, monitoring the accuracy during the abstraction process is also required. Recent studies reporting research results based on MRA rarely reported data quality assurance or control measures, and even less frequently reported data quality metrics with research results. Given the demonstrated variability, these methods and measures should be reported with research results.</p></div

Comparison of factors mentioned in the Delphi top 27% and the literature top 26%.

<p>Comparison of factors mentioned in the Delphi top 27% and the literature top 26%.</p