Best Practices for Measuring the Modulation Transfer Function of Video Endoscopes.

Endoscopes are crucial for assisting in surgery and disease diagnosis, including the early detection of cancer. The effective use of endoscopes relies on their optical performance, which can be characterized with a series of metrics such as resolution, vital for revealing anatomical details. The modulation transfer function (MTF) is a key metric for evaluating endoscope resolution. However, the 2020 version of the ISO 8600-5 standard, while introducing an endoscope MTF measurement method, lacks empirical validation and excludes opto-electronic video endoscopes, the largest family of endoscopes. Measuring the MTF of video endoscopes requires tailored standards that address their unique characteristics. This paper aims to expand the scope of ISO 8600-5:2020 to include video endoscopes, by optimizing the MTF test method and addressing parameters affecting measurement accuracy. We studied the effects of intensity and uniformity of image luminance, chart modulation compensation, linearity of image digital values, auto gain control, image enhancement, image compression and the region of interest dimensions on images of slanted-edge test charts, and thus the MTF based on these images. By analyzing these effects, we provided recommendations for setting and controlling these factors to obtain accurate MTF curves. Our goal is to enhance the standard's relevance and effectiveness for measuring the MTF of a broader range of endoscopic devices, with potential applications in the MTF measurement of other digital imaging devices.

Facile preparation of porphyrin@g-C3N4/Ag nanocomposite for improved photocatalytic degradation of organic dyes in aqueous solution.

In the quest of improving the photocatalytic efficiency of photocatalysts, the combination of two and more semiconductors recently has garnered significant attention among scientists in the field. The doping of conductive metals is also an effective pathway to improve photocatalytic performance by avoiding electron/hole pair recombination and enhancing photon energy absorption. This work presented a design and fabrication of porphyrin@g-C3N4/Ag nanocomposite using acid-base neutralization-induced self-assembly approach from monomeric porphyrin and g-C3N4/Ag material. g-C3N4/Ag material was synthesized by a green reductant of Cleistocalyx operculatus leaf extract. Electron scanning microscopy (SEM), X-ray diffraction (XRD), FT-IR spectroscopy, and UV-vis spectrometer were utilized to analyse the properties of the prepared materials. The prepared porphyrin@g-C3N4/Ag nanocomposite showed well integration of porphyrin nanostructures on the g-C3N4/Ag's surface, in which porphyrin nanofiber was of the diameter in nanoscales and the length of several micrometers, and Ag NPs had an average particle size of less than 20 nm. The photocatalytic behavior of the resultant nanocomposite was tested for the degradation of Rhodamine B dye, which exhibited a remarkable RhB photodegrading percentage. The possible mechanism for photocatalysis of the porphyrin@g-C3N4/Ag nanocomposite toward Rhodamine B dye was also proposed and discussed.

Efficient Synthesis of Folate-Conjugated Hollow Polymeric Capsules for Accurate Drug Delivery to Cancer Cells.

This study presents an efficient and systematic approach to synthesize bioapplicable porous hollow polymeric capsules (HPCs). The hydroxyl-functionalized nanoporous polymers with hollow capsular shapes could be generated via the moderate Friedel-Crafts reaction without using any hard or soft template. The numerous primitive hydroxyl groups on these HPCs were further converted to carboxyl groups. Owing to the abundance of highly branched carboxyl groups on the surface of the HPCs, biomolecules [such as folic acid (FA)] could be covalently decorated on these organic capsules (FA-HPCs) for drug delivery applications. The intrinsic hollow porosities and specific targeting agent offered a maximum drug encapsulation efficiency of up to 86% and drug release of up to 50% in 30 h in an acidic environment. The in vitro studies against cancer cells demonstrated that FA-HPCs exhibited a more efficient cellular uptake and intracellular doxorubicin release than bare HPCs. This efficient approach to fabricate carbonyl-functionalized hollow organic capsules may open avenues for a new type of morphological-controlled nanoporous polymers for various potential bioengineering applications.

Delayed Cord Clamping and Umbilical Cord Milking among Infants in California Neonatal Intensive Care Units.

OBJECTIVE: To assess the current practice of delayed cord clamping (DCC) and to determine patient and hospital factors that predict DCC. STUDY DESIGN: The California Perinatal Quality Care Collaborative (CPQCC) collects data on preterm and acutely ill infants. In 2016, 52 CPQCC neonatal intensive care units (NICUs) collected data on DCC. Hospital and patient characteristics were analyzed using multivariable logistic regression. RESULTS: Of 5,332 deliveries, 1,555 (29%) newborns received DCC. Hospital rates ranged from 0 to 74.5% and increased from 21 to 37% throughout 2016. Infants delivered at <32 weeks or with birth weight <1,500 g were more likely to receive DCC (odds ratio: 2.80; 95% confidence interval: 2.33, 3.36). Cesarean delivery was associated with less likelihood of DCC (odds ratio: 0.68; 95% confidence interval: 0.59, 0.79). After risk adjustment, 17 (33%) hospitals had higher than expected DCC rate. Hospitals with less than 50 NICU beds are more likely to practice DCC, whereas Level 3 American Academy of Pediatrics NICUs, nonprofit owned hospitals, and teaching institutions were less likely to practice DCC (p < 0.001). CONCLUSION: There are opportunities to implement quality improvement activities to increase DCC rates.

Cytomegalovirus Infection among Infants in Neonatal Intensive Care Units, California, 2005 to 2016.

AIM: The main purpose of this article is to assess trends in cytomegalovirus (CMV) infection reported among infants in California neonatal intensive care units (NICUs) during 2005 to 2016. STUDY DESIGN: The California Perinatal Quality Care Collaborative collects data on all very low birth weight (VLBW, birth weight ≤ 1,500 g) and acutely ill infants > 1,500 g, representing 92% of NICUs in California. We compared clinical characteristics and length of hospital stay among infants with and without reported CMV infection (CMV-positive viral culture or polymerase chain reaction). RESULTS: During 2005 to 2016, CMV infection was reported in 174 VLBW infants and 145 infants > 1,500 g, or 2.7 (range: 1.5-4.7) and 1.2 (range: 0.8-1.7) per 1,000 infants, respectively (no significant annual trend). Among infants > 1,500 g, 12 (8%) versus 4,928 (4%) of those reported with versus without CMV infection died (p < 0.05). The median hospital stay was significantly longer among infants reported with versus without CMV infection for both VLBW infants (98 vs. 46 days) and infants > 1,500 g (61 vs. 14 days) (p < 0.001). CONCLUSION: Reports of CMV infection remained stable over a 12-year period. Although we were not able to assess whether infection was congenital or postnatal, CMV infection among infants > 1,500 g was associated with increased mortality.

Discovery of the pan-genotypic hepatitis C virus NS3/4A protease inhibitor voxilaprevir (GS-9857): A component of Vosevi®.

Treatment of hepatitis C virus (HCV) infection has been historically challenging due the high viral genetic complexity wherein there are eight distinct genotypes and at least 86 viral subtypes. While HCV NS3/4A protease inhibitors are an established treatment option for genotype 1 infection, limited coverage of genotypes 2 and/or 3 combined with serum alanine transaminase (ALT) elevations for some compounds has limited the broad utility of this therapeutic class. Our discovery efforts were focused on identifying an NS3/4A protease inhibitor with pan-genotypic antiviral activity, improved coverage of resistance associated substitutions, and a decreased risk of hepatotoxicity. Towards this goal, distinct interactions with the conserved catalytic triad of the NS3/4A protease were identified that improved genotype 3 antiviral activity. We further discovered that protein adduct formation strongly correlated with clinical ALT elevation for this therapeutic class. Improving metabolic stability and decreasing protein adduct formation through structural modifications ultimately resulted in voxilaprevir. Voxilaprevir, in combination with sofosbuvir and velpatasvir, has demonstrated pan-genotypic antiviral clinical activity. Furthermore, hepatotoxicity was not observed in Phase 3 clinical trials with voxilaprevir, consistent with our design strategy. Vosevi® (sofosbuvir, velpatasvir, and voxilaprevir) is now an approved pan-genotypic treatment option for the most difficult-to-cure individuals who have previously failed direct acting antiviral therapy.

Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®.

Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa®, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi®, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.

Effect of polyDADMAC on aggregation of clay-size particles in red mud: Implications for immobilization practices.

PolyDADMAC (PD) is a high charge density cationic polymer of diallyldimethylammonium chloride which has been recently developed as a coagulant in water purification. As PD has high affinity to fine negatively-charged colloids, it is worth to ascertain if PD can affect surface properties of clay-size particles in red mud waste and be applied to develop immobilization techniques for red mud storage areas. In the current study, a test tube method in combination with surface charge measurement was used for determination of the colloidal properties of a red mud sample under the variation of PD, soluble Al and Si, and variable pH conditions. Observations for the PD concentration range from 0.25 to 2.0 mM revealed that PD can increase surface charge and enhance aggregation or at least shift the aggregation zone to higher pH. This suggests a possible application of PD for immobilization of red mud in alkaline condition. It was also found that soluble Al and Si acted to modify the effect of PD and aggregation properties of red mud. While soluble Si supported aggregation, Al appeared as an enhancer for dispersion of red mud. It implies that development of PD-based techniques for immobilization of red mud needs to consider the effects of soluble Al and Si.

Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A.

Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 µg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤ 16 µg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥ 13 mm to a 5-µg azithromycin disk identified S. Typhi isolates with an MIC of ≤ 16 µg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤ 16 µg/ml or disk inhibition zone size of ≥ 13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 µg/ml and to determine MIC and disk breakpoints for S. Paratyphi A.

Synthesis of Polyether, Poly(Ether Carbonate) and Poly(Ether Ester) Polyols Using Double Metal Cyanide Catalysts Bearing Organophosphorus Complexing Agents.

We developed a series of Zn(II)-Co(III) double metal cyanide (DMC) catalysts with exceptional activity for the ring-opening polymerization of various cyclic monomers by employing diverse organophosphorus compounds as complexing agents (CAs). The chemical structure and composition of DMC catalysts were investigated by commonly used analysis such as infrared and X-ray photoelectron spectroscopies, and elemental analysis combining with in situ NMR analysis to determine the complexation types of organophosphorus compounds the catalyst framework. The resulting catalysts exhibited very high turnover frequencies (up to 631.4 min-1) in the ring-opening polymerization (ROP) of propylene oxide and good efficiency for the ROP of ε-caprolactone. The resultant polyester polyols are suitable to use as an macroinitiator to produce well-defined poly(ester ether) triblock copolymers of 1800-6600 g mol-1 and dispersity of 1.16-1.37. Additionally, the DMC catalysts bearing organophosphorus compounds CAs exhibited remarkable selectivity for the copolymerization of PO with CO2, yielding poly(ether carbonate) polyols with carbonate contents up to 34.5%. This study contributes to the development of efficient DMC catalytic systems that enable the synthesis of high-quality polyols for various applications.

Highly Active Heterogeneous Double Metal Cyanide Catalysts for Ring-Opening Polymerization of Cyclic Monomers.

A series of heterogeneous Zn-Co double metal cyanide (DMC) catalysts were investigated for ring-opening polymerization (ROP) of various cyclic monomers. Notably, inexpensive and commonly used organic solvents such as acetone, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, nitromethane, and 1-methylpyrrolidin-2-one were very effective complexing agents for the preparation of DMC catalysts, showing high catalytic activity for the ROP of propylene oxide, ε-caprolactone, and δ-valerolactone. The chemical structures and compositions of the resultant catalysts were determined using various techniques such as FT-IR, X-ray photoelectron spectroscopy, powder X-ray diffraction, and elemental analysis. α,ω-Hydroxyl-functionalized polyether and polyester polyols with high yields and tunable molecular weights were synthesized in the presence of various initiators to control functionality. Kinetic studies of the ROP of δ-valerolactone were also performed to confirm the reaction mechanism.

Green synthesis of a photocatalyst Ag/TiO2 nanocomposite using Cleistocalyx operculatus leaf extract for degradation of organic dyes.

Green synthesis has emerged as a sustainable approach for the fabrication of nanomaterials in the last few decades. Leaf extracts have been considered low-cost and highly efficient reactants for the synthesis of nanoparticles. In this study, an aqueous extract of Cleistocalyx operculatus leaves was employed as a reductant to synthesize Ag/TiO2 nanocomposites. The morphology, structure, and interface interaction of the Ag/TiO2 nanocomposites were investigated by (i) X-ray diffraction (XRD) to determine the crystallinity, (ii) scanning electron microscopy (SEM) to determine the morphologies, (iii) energy dispersive X-ray spectroscopy (EDX) to determine the elemental composition and distribution, and (iv) diffuse reflectance spectroscopy (DRS) to understand the optical properties. The results showed that Ag nanoparticles (AgNPs) with particle sizes of 20-40 nm homogeneously covered the surface of the TiO2 nanoparticles. The green-synthesized Ag/TiO2 nanocomposite also exhibited an excellent photodegradation ability for Rhodamine B with a removal percentage up to 91.4% after 180 min of photocatalytic reaction.

Self-Assembly of Porphyrin Nanofibers on ZnO Nanoparticles for the Enhanced Photocatalytic Performance for Organic Dye Degradation.

Synthesizing novel photocatalysts that can effectively harvest photon energy over a wide range of the solar spectrum for practical applications is vital. Porphyrin-derived nanostructures with properties similar to those of chlorophyll have emerged as promising candidates to meet this requirement. In this study, tetrakis(4-carboxyphenyl) porphyrin (TCPP) nanofibers were formed on the surface of ZnO nanoparticles using a simple self-assembly approach. The obtained ZnO/TCPP nanofiber composites were characterized via scanning electron microscopy, X-ray diffraction analysis, and ultraviolet-visible absorbance and reflectance measurements. The results demonstrated that the ZnO nanoparticles with an average size of approximately 37 nm were well integrated in the TCPP nanofiber matrix. The resultant composite showed photocatalytic activity of ZnO and TCPP nanofibers concomitantly, with band gap energies of 3.12 and 2.43 eV, respectively. The ZnO/TCPP photocatalyst exhibited remarkable photocatalytic performance for RhB degradation with a removal percentage of 97% after 180 min of irradiation under simulated sunlight because of the synergetic activity of ZnO and TCPP nanofibers. The dominant active species participating in the photocatalytic reaction were •O2 - and OH•, resulting in enhanced charge separation by exciton-coupled charge-transfer processes between the hybrid materials.

New TiO2-doped Cu-Mg spinel-ferrite-based photocatalyst for degrading highly toxic rhodamine B dye in wastewater.

The quest for finding an effective photocatalyst for environmental remediation and treatment strategies is attracting considerable attentions from scientists. In this study, a new hybrid material, Cu0.5Mg0.5Fe2O4-TiO2, was designed and fabricated using coprecipitation and sol-gel approaches for degrading organic dyes in wastewater. The prepared hybrid materials were fully characterized using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The results revealed that the Cu0.5Mg0.5Fe2O4-TiO2 hybrid material was successfully synthesized with average particle sizes of 40.09 nm for TiO2 and 27.9 nm for Cu0.5Mg0.5Fe2O4. As the calculated bandgap energy of the hybrid material was approximately 2.86 eV, it could harvest photon energy in the visible region. Results indicate that the Cu0.5Mg0.5Fe2O4-TiO2 also had reasonable magnetic properties with a saturation magnetization value of 11.2 emu/g, which is a level of making easy separation from the solution by an external magnet. The resultant Cu0.5Mg0.5Fe2O4-TiO2 hybrid material revealed better photocatalytic performance for rhodamine B dye (consistent removal rate in the 13.96 × 10-3 min-1) compared with free-standing Cu0.5Mg0.5Fe2O4 and TiO2 materials. The recyclability and photocatalytic mechanism of Cu0.5Mg0.5Fe2O4-TiO2 are also well discussed.

Targeting Oncogene mRNA Translation in B-Cell Malignancies with eFT226, a Potent and Selective Inhibitor of eIF4A.

The PI3K/AKT/mTOR pathway is often activated in lymphoma through alterations in PI3K, PTEN, and B-cell receptor signaling, leading to dysregulation of eIF4A (through its regulators, eIF4B, eIF4G, and PDCD4) and the eIF4F complex. Activation of eIF4F has a direct role in tumorigenesis due to increased synthesis of oncogenes that are dependent on enhanced eIF4A RNA helicase activity for translation. eFT226, which inhibits translation of specific mRNAs by promoting eIF4A1 binding to 5'-untranslated regions (UTR) containing polypurine and/or G-quadruplex recognition motifs, shows potent antiproliferative activity and significant in vivo efficacy against a panel of diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma models with ≤1 mg/kg/week intravenous administration. Evaluation of predictive markers of sensitivity or resistance has shown that activation of eIF4A, mediated by mTOR signaling, correlated with eFT226 sensitivity in in vivo xenograft models. Mutation of PTEN is associated with reduced apoptosis in vitro and diminished efficacy in vivo in response to eFT226. In models evaluated with PTEN loss, AKT was stimulated without a corresponding increase in mTOR activation. AKT activation leads to the degradation of PDCD4, which can alter eIF4F complex formation. The association of eFT226 activity with PTEN/PI3K/mTOR pathway regulation of mRNA translation provides a means to identify patient subsets during clinical development.

Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis.

BACKGROUND: It is uncertain whether all adults with bacterial meningitis benefit from treatment with adjunctive dexamethasone. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone in 435 patients over the age of 14 years who had suspected bacterial meningitis. The goal was to determine whether dexamethasone reduced the risk of death at 1 month and the risk of death or disability at 6 months. RESULTS: A total of 217 patients were assigned to the dexamethasone group, and 218 to the placebo group. Bacterial meningitis was confirmed in 300 patients (69.0%), probable meningitis was diagnosed in 123 patients (28.3%), and an alternative diagnosis was made in 12 patients (2.8%). An intention-to-treat analysis of all the patients showed that dexamethasone was not associated with a significant reduction in the risk of death at 1 month (relative risk, 0.79; 95% confidence interval [CI], 0.45 to 1.39) or the risk of death or disability at 6 months (odds ratio, 0.74; 95% CI, 0.47 to 1.17). In patients with confirmed bacterial meningitis, however, there was a significant reduction in the risk of death at 1 month (relative risk, 0.43; 95% CI, 0.20 to 0.94) and in the risk of death or disability at 6 months (odds ratio, 0.56; 95% CI, 0.32 to 0.98). These effects were not found in patients with probable bacterial meningitis. Results of multivariate analysis indicated that dexamethasone treatment for patients with probable bacterial meningitis was significantly associated with an increased risk of death at 1 month, an observation that may be explained by cases of tuberculous meningitis in the treatment group. CONCLUSIONS: Dexamethasone does not improve the outcome in all adolescents and adults with suspected bacterial meningitis; a beneficial effect appears to be confined to patients with microbiologically proven disease, including those who have received prior treatment with antibiotics. (Current Controlled Trials number, ISRCTN42986828 [controlled-trials.com] .).

Effective Removal of Pb(II) from Aqueous Media by a New Design of Cu-Mg Binary Ferrite.

Metal oxides and their composites have been extensively studied as effective adsorbents for the removal of heavy metals from aqueous solutions in environmental remediation. In this work, Cu0.5Mg0.5Fe2O4 was synthesized by a co-precipitation method followed by calcination (900 °C) and investigated for Pb(II) adsorption. The resultant samples were characterized by various analytical techniques including X-ray diffraction, N2 adsorption-desorption, scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The results revealed that single-phase cubic spinel was obtained by the calcination of as-synthesized samples at a temperature of 900 °C. Cu0.5Mg0.5Fe2O4 ferrite is a mesoporous material with a surface area, a total pore volume, and an average pore size of 41.3 m2/g, 0.2 cm3/g, and 15.1 nm, respectively. Pb(II) adsorption on Cu0.5Mg0.5Fe2O4 fitted well to the Langmuir model, indicating monolayer adsorption with a maximum capacity of 57.7 mg/g. The pseudo-second-order kinetic model can exactly describe Pb(II) adsorption with the normalized standard deviation (Δq) of 1.24%. The obtained results confirmed that the Cu0.5Mg0.5Fe2O4 ternary oxides exhibit a high adsorption capacity toward Pb(II), thanks to the increase in active adsorptive sites of ferrite.

Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase.

Dysregulation of protein translation is a key driver for the pathogenesis of many cancers. Eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase, is a critical component of the eIF4F complex, which regulates cap-dependent protein synthesis. The flavagline class of natural products (i.e., rocaglamide A) has been shown to inhibit protein synthesis by stabilizing a translation-incompetent complex for select messenger RNAs (mRNAs) with eIF4A. Despite showing promising anticancer phenotypes, the development of flavagline derivatives as therapeutic agents has been hampered because of poor drug-like properties as well as synthetic complexity. A focused effort was undertaken utilizing a ligand-based design strategy to identify a chemotype with optimized physicochemical properties. Also, detailed mechanistic studies were undertaken to further elucidate mRNA sequence selectivity, key regulated target genes, and the associated antitumor phenotype. This work led to the design of eFT226 (Zotatifin), a compound with excellent physicochemical properties and significant antitumor activity that supports clinical development.

5,5'- and 6,6'-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase.

The discovery of 5,5'- and 6,6'-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC50 <0.10 microM). In vitro DMPK data for selected compounds as well as crystal structures of representative inhibitors complexed with the NS5B protein are also disclosed.