Impact assessment in a non-government organisation

<p>Supplemental_figure for A Simple Scoring System Using the Red Blood Cell Distribution Width, Delta Neutrophil Index, and Platelet Count to Predict Mortality in Patients With Severe Sepsis and Septic Shock by Yong Chan Kim, Je Eun Song, Eun Jin Kim, Heun Choi, Woo Yong Jeong, In Young Jung, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Young Goo Song, and June Myung Kim in Journal of Intensive Care Medicine</p

Supplemental_table_2 - A Simple Scoring System Using the Red Blood Cell Distribution Width, Delta Neutrophil Index, and Platelet Count to Predict Mortality in Patients With Severe Sepsis and Septic Shock

<p>Supplemental_table_2 for A Simple Scoring System Using the Red Blood Cell Distribution Width, Delta Neutrophil Index, and Platelet Count to Predict Mortality in Patients With Severe Sepsis and Septic Shock by Yong Chan Kim, Je Eun Song, Eun Jin Kim, Heun Choi, Woo Yong Jeong, In Young Jung, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Young Goo Song, and June Myung Kim in Journal of Intensive Care Medicine</p

<i>In Silico</i> HTS and Structure Based Optimization of Indazole-Derived ULK1 Inhibitors

We present the outcome of an <i>in silico</i> high throughput screen (HTS) and optimization of a small molecule Unc-51-Like Kinase 1 (ULK1) inhibitor hit, <b>SR-17398</b>, with an indazole core. Docking studies guided design efforts that led to inhibitors with increased activity vs ULK1 (IC₅₀ < 50 nM). The most advanced molecules in this inhibitor series (<b>3a</b> and <b>3g</b>) hold promise for further development into selective ULK1 molecular probes to interrogate the biology of ULK1 and to assess whether selectively targeting autophagy is an effective anticancer strategy

Correlation between LSM values and other variables.

<p><b>NOTE.</b>^aPearson’s correlation coefficient, ^bCorrelation analyses in only patients who has ever been received each antiretroviral drug, ^cSpearman’s ρ. LSM, liver stiffness measurement; cART, combined antiretroviral treatment; INR, international normalized ratio; NRTIs, nucleoside analogue reverse transcriptase inhibitors; NNRTIs, non-nucleoside analogue reverse transcriptase inhibitors; PIs, protease inhibitors.</p

Rational Development of 4‑Aminopyridyl-Based Inhibitors Targeting Trypanosoma cruzi CYP51 as Anti-Chagas Agents

A new series of 4-aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (<i>Tc</i>CYP51) has been developed using structure-based drug design as well as structure–property relationship (SPR) analyses. The screening hit starting point, LP10 (<i>K</i>_D ≤ 42 nM; EC₅₀ = 0.65 μM), has been optimized to give the potential leads <b>14t</b>, <b>27i</b>, <b>27q</b>, <b>27r</b>, and <b>27t</b>, which have low-nanomolar binding affinity to <i>Tc</i>CYP51 and significant activity against T. cruzi amastigotes cultured in human myoblasts (EC₅₀ = 14–18 nM for <b>27i</b> and <b>27r</b>). Many of the optimized compounds have improved microsome stability, and most are selective against human CYPs 1A2, 2D6, and 3A4 (<50% inhibition at 1 μM). A rationale for the improvement in microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of <b>14t</b> with the Trypanosoma brucei CYP51 (<i>Tb</i>CYP51) orthologue has been characterized by X-ray structure analysis

Comparisons of baseline characteristics and cumulative exposure durations of antiretroviral drugs between patients with normal and abnormal LSM values.

<p><b>NOTE.</b> Data are expressed as mean ± SD or number (percent). ^aIndependent sample two T-test, ^bFisher’s exact test, ^cChi-square test, and ^dMann-Whitney U-test were used.^eThe undetectable range was defined as fewer than 20 copies/mL. LSM, liver stiffness measurement; cART, combined antiretroviral treatment; INR, international normalized ratio; NNRTI, non-nucleoside analogue reverse transcriptase inhibitor; cART, combined antiretroviral treatment; PI, protease inhibitors; NRTI, nucleoside analogue reverse transcriptase inhibitor.</p

Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors

We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (<b>10d</b> and (<i>S</i>)-<b>17b</b>) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound <b>5</b> in complex with MMP-13 with published structures of known MMP-13·inhibitor complexes followed by molecular design and synthesis of potent but nonselective zinc-chelating MMP inhibitors (e.g., <b>10a</b> and <b>10b</b>). After demonstrating that the pharmacophores of the chelating inhibitors (<i>S</i>)-<b>10a</b>, (<i>R</i>)-<b>10a</b>, and <b>10b</b> were binding within the MMP-13 active site, the Zn²⁺ chelating unit was replaced with nonchelating polar residues that bridged over the Zn²⁺ binding site and reached into a solvent accessible area. After two rounds of structural optimization, these design approaches led to small molecule MMP-13 inhibitors <b>10d</b> and (<i>S</i>)-<b>17b</b>, which bind within the substrate-binding site of MMP-13 and surround the catalytically active Zn²⁺ ion without chelating to the metal. These compounds exhibit at least 500-fold selectivity versus other MMPs

Distribution of LSM values among all study participants.

<p><b>NOTE.</b> The dotted line indicates the cutoff value for abnormal LSM (5.3 kPa). LSM, liver stiffness measurement; kPa, kilopascal.</p

Recruitment flow of study participants for this study.

<p><b>NOTE.</b> LSM, liver stiffness measurement; HBV, hepatitis B virus; HCV, hepatitis C virus; HAV, hepatitis A virus; OI, opportunistic infection; AIDS, acquired immunodeficiency syndrome; cART, combined antiretroviral treatment.</p

Percentage of patients with abnormal LSM values according to cutoff values of the cumulative exposure duration of boosted-PIs (a) and γ-GT level (b).

<p>Percentage of patients with abnormal LSM values according to cutoff values of the cumulative exposure duration of boosted-PIs (a) and γ-GT level (b).</p