bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Pyridazines: Synthesis, Characterization, Cytotoxicity, Substrate Promiscuity, and Molecular Docking
Authors: Mustafa Muhamad , Mostafa Yaser A.
Published: April 2020

A facile and convenient synthesis of new pyridazines suitable for use as antimicrobial agents was reported. The hydrazide intermediate was coupled with various benzaldehydes and/or acetophenones and cyclized instantaneously to afford target pyridazine derivatives. The structures of new pyridazines were confirmed by IR, 1H‐ and 13C‐NMR, elemental analysis in addition to representative LC/MS. Antimicrobial activity was screened against 10 bacterial and fungal strains. The new pyridazines showed strong to very strong antibacterial activity against Gram‐negative (GNB) bacteria, while none of them showed significant antifungal activity at the same concentration range. Chloro derivatives exhibited the highest antibacterial activity with MICs (0.892–3.744 μg/mL) lower than that of chloramphenicol (2.019–8.078 μg/mL) against E. coli, P. aeruginosa, and S. marcescens. Prediction of ADME parameters, pharmacokinetics, and substrate promiscuity revealed that these new pyridazines could be promising drug candidates. Cytotoxic studies on rat hepatocytes showed how much safe these new pyridazines on living organisms (IC50>64 μg/mL). MOE docking studies showed a good overlay of these new pyridazines with co‐crystallized ligand within an E. coli DNA gyrase subunit B active sites (4KFG).
Achillea filipendulinaLam.: Chemical Constituents and Antimicrobial Activities of Essential Oil of Stem, Leaf, and Flower
Authors: Aminkhani Ali , Sharifi Sina , Ekhtiyari Shirin
Published: April 2020

In this study, we extracted the essential oils of the stem, leaf, and flower of Achillea filipendulina, analyzed them, and studied their antibacterial properties. Of 16, 53, and 35 compounds identified in the stem, leaf, and flowers, respectively, only five are present in all three segments of the plant. The essential oil of the stem was mainly composed of neryl acetate, spathulenol, carvacrol, santolina alcohol, and trans‐caryophyllene oxide. However, the main identified components of leaf were 1,8‐cineole, camphor, ascaridole, trans‐isoascaridole, and piperitone oxide and the main components of the flower oil were ascaridole, trans‐isoascaridole, 1,8‐cineole, p‐cymene, and camphor. The extracted oil from different segments demonstrated varying antibacterial properties against both Gram‐positive and Gram‐negative bacteria, demonstrated by disk, minimum inhibitory concentration, and minimum bactericidal concentration methods. These suggest that the application of all segments of aerial parts of A. filipendulina may have a better therapeutic effect in fighting pathogenic systems.
Simple Flow Injection Analysis System Coupled to Multiple‐Pulse Amperometry and a Boron‐Doped Diamond Electrode for the Simultaneous Determination of Sunset Yellow and Aspartame
Authors: Deroco Patrícia B. , Medeiros Roberta A. , Rocha‐Filho Romeu C. , Fatibello‐Filho Orlando
Published: April 2020

The first electroanalytical method for the simultaneous determination of the colorant sunset yellow (SY) and the sweetener aspartame (AS) in commercial food samples is proposed using flow injection analysis coupled to multiple‐pulse amperometry (FIA‐MPA) and an anodically pretreated boron‐doped diamond electrode (APT‐BDDE). Dual‐potential waveforms are applied as a function of time: Edet.1=1.30 V/150 s for the oxidation only of SY, and Edet.2=1.70 V/200 s for the oxidation of both analytes. Linear analytical curves were obtained in the concentration range of 0.15–25.0 μmol L−1 for SY and 0.25–25.0 μmol L−1 for AS, with a calculated limit of detection of 0.04 μmol L−1 for both analytes. The proposed method presented good precision and enabled the simultaneous determination of SY and AS in samples of jelly and juice powders with a good accuracy (at a 95 % confidential level) when compared to an HPLC method. The proposed FIA‐MPA method is simple and fast, with an analytical frequency of 120 determinations per hour, being an attractive option for routine simultaneous determinations of SY and AS.
Light‐Induced Uncaging for Time‐Resolved Observations of Biochemical Reactions by MAS NMR Spectroscopy
Authors: de Mos Julian , Jakob Andreas , Becker‐Baldus Johanna , Heckel Alexander , Glaubitz Clemens
Published: April 2020

Light‐induced activation of biomolecules by uncaging of photolabile protection groups has found many applications for triggering biochemical reactions with minimal perturbations directly within cells. Such an approach might also offer unique advantages for solid‐state NMR experiments on membrane proteins for initiating reactions within or at the membrane directly within the closed MAS rotor. Herein, we demonstrate that the integral membrane protein E. coli diacylglycerol kinase (DgkA), which catalyzes the phosphorylation of diacylglycerol, can be controlled by light under MAS‐NMR conditions. Uncaging of NPE‐ATP or of lipid substrate NPE‐DOG by in situ illumination triggers its enzymatic activity, which can be monitored by real‐time 31P‐MAS NMR. This proof‐of‐concept illustrates that combining MAS‐NMR with uncaging strategies and illumination methods offers new possibilities for controlling biochemical reactions at or within lipid bilayers.
Site‐Directed Antibody Immobilization by Resorc[4]arene‐Based Immunosensors
Authors: Quaglio Deborah , Mangiardi Laura , Venditti Giulia , Del Plato Cristina , Polli Francesca , Ghirga Francesca , Favero Gabriele , Pierini Marco , Botta Bruno , Mazzei Franco
Published: April 2020

One of the main problems in the development of immunosensors is to overcome the complexity of binding antibodies to the sensor surface. Most immobilizing methods lead to a random orientation of antibodies with a lower binding site density and immunoaffinity. In order to control the orientation of antibody immobilization, several resorc[4]arene derivatives were designed and synthesized. After the spectroscopic characterization of resorc[4]arene self‐assembled monolayers (SAMs) onto gold films, the surface coverage and the orientation of insulin antibody (Ab‐Ins) were assessed by a surface plasmon resonance (SPR) technique and compared with a random immobilization method. Experimental results combined with theoretical studies confirmed the dipole–dipole interaction as an important factor in antibody orientation and demonstrated the importance of the upper rim functionalization of resorcarenes. Accordingly, resorcarene 5 showed a major binding force towards Ab‐Ins thanks to the H‐bond interactions with the amine protein groups. Based on these findings, the resorcarene‐based immunosensor is a powerful system with improved sensitivity providing new insight into sensor development.
Cornforth–Evans Transition States in Stereocontrolled Allylborations of Epoxy Aldehydes
Authors: Freund Robert R. A. , van den Borg Matthias , Gaissmaier Daniel , Schlosser Robin , Jacob Timo , Arndt Hans‐Dieter
Published: April 2020

Allylboration reactions rank among the most reliable tools in organic synthesis. Herein, we report a general synthesis of trifunctionalized allylboronates and systematic investigations of their stereocontrolled transformations with substituted aldehyde substrates, in order to efficiently access diverse, highly substituted target substrates. A peculiar transition in stereocontrol was observed from the polar Felkin–Anh (PFA) to the Cornforth–Evans (CE) model for alkoxy‐ and epoxy‐substituted aldehydes. CE‐type transition states were uniformly identified as minima in advanced, DFT‐based computational studies of allylboration reactions of epoxy aldehydes, conforming well to the experimental data, and highlighting the underestimated relevance of this model. Furthermore, a mechanism‐based rationale for the substitution pattern of the epoxide was delineated that ensures high levels of stereocontrol and renders α,β‐epoxy aldehydes generally applicable substrates for target synthesis.
When Small becomes Too Big: Expanding the Use of In‐Cell Solid‐State NMR Spectroscopy
Authors: Narasimhan Siddarth , Folkers Gert E. , Baldus Marc
Published: April 2020

Solution‐state NMR spectroscopy has become a powerful tool to study soluble proteins in cells, provided that they tumble sufficiently fast. In addition, cryo‐electron tomography (cryo‐ET) has recently displayed a tremendous potential to probe structures of large proteins and assemblies in their native cellular environments. However, challenges remain to obtain atomic‐level information in native cell settings for proteins that are small, disordered, or are strongly engaged in intermolecular interactions. In this Minireview, we discuss recent progress in using sensitivity enhanced solid‐state NMR spectroscopy methods in the context of cellular structural biology.
Nonlinear interaction phenomenon of dust acoustic solitary and shock waves in dusty plasma
Authors: Moinuddin Abu Shahed Mohammad , Alam Mohammad Shah , Talukder Mamunur Rashid
Published: April 2020

The effects of head‐on collision on dust acoustic (DA) solitary and shock waves in dusty plasma are investigated considering positively charged inertial dust, Boltzmann distributed negatively charged heavy ions, positively charged light ions, and superthermal electrons in the plasma system. The nonlinear Korteweg‐de‐Vries (KdV) Burger equations are derived taking the extended Poincaré‐Lighthill‐Kuo method into account to study the characteristic properties of nonlinearity and production of solitary shock due to collisions. The study reveals that the amplitudes and widths of the DA shock waves are decreasing with increasing viscosity, electron to dust density ratio, and dust to ion temperature ratio, while they are increasing due to the presence of superthermal electrons. The nonlinearity of DA waves are enhanced with increasing density ratio of electron to dust and temperature ratio of dust to ion and electron, respectively, but it is reducing with superthermal electrons. The phase shifts of DA solitary waves are found to decrease with rising superthermality of electrons and increase with the density ratio of electron to
dust.
Cytohistological correlation in patients with atypical glandular cells on Papanicolaou test in a Chilean population
Authors: González‐Espinoza Daniela , Ponce Camus Katherine , Meneses Pérez Ives , Molina Cruz Carla
Published: April 2020

The standard screening test for detecting cervical lesions and cancers is a Papanicolaou (Pap) smear. While squamous cell abnormalities remain the most common positive Pap test result, cytologic findings of glandular cell abnormalities have become more frequent in recent decades. The 2014 Bethesda System for reporting cervical cytology includes the classification “atypical glandular cells” (AGC). AGC have morphological abnormalities that fall outside the range of reactive changes, but are insufficient for a diagnosis of invasive adenocarcinoma. In several histologic follow‐up studies, most AGC cases were found to represent a benign condition. In the current study, we evaluate the significance of AGC cytology findings by analyzing the histologic follow‐up results of a large number of patients with AGC. Most patients with AGC in this study were found to have a significant lesion on follow‐up (63.9%), with negative histologic results in only 36.1% of patients. Among patients with significant lesions, the most common result was low‐grade squamous intraepithelial lesion (26.6%), followed by high‐grade squamous intraepithelial lesion (23.2%). This provides further evidence to support the Chilean Clinical Guidelines for Cervical Cancer, which recommends diagnostic follow‐up studies in all women with AGC to minimize the chance of undetected serious cervical disease.
Assessing the genetic diversity in Argopecten nucleus (Bivalvia: Pectinidae), a functional hermaphrodite species with extremely low population density and self‐fertilization: Effect of null alleles
Authors: Barros Judith , Winkler Federico M. , Velasco Luz Adriana
Published: April 2020

Argopecten nucleus is a functional hermaphroditic pectinid species that exhibits self‐fertilization, whose natural populations have usually very low densities. In the present study, the genetic diversity of a wild population from Neguanje Bay, Santa Marta (Colombia), was estimated using microsatellite markers, and the effect of the presence of null alleles on this estimation was assessed. A total of 8 microsatellite markers were developed, the first described for this species, and their amplification conditions were standardized. They were used to determine the genotype of 48 wild individuals from Naguanje Bay, and 1,010 individuals derived from the offspring of 38 directed crosses. For each locus, the frequencies of the identified alleles, including null alleles, were estimated using the statistical package Micro‐Checker, and the parental genotypes were confirmed using segregation analysis. Three to 8 alleles per locus with frequencies from 0.001 to 0.632 were detected. The frequencies of null alleles ranged from 0.10 to 0.45, with Ho from 0.0 to 0.79, and He from 0.53 to 0.80. All loci were in H‐W disequilibrium. The null allele frequencies values were high, with lower estimations using segregation analysis than estimated using Micro‐Checker. The present results show high levels of population genetic diversity and indicate that null alleles were not the only cause of deviation from H‐W equilibrium in all loci, suggesting that the wild population under study presents signs of inbreeding and Wahlund effect.
Evaluation of harmonic current effect and distribution line voltage control ability of reactive power control by use of power factor correction converter in consumer load
Authors: Kondo Ken‐ichi , Baba Jumpei
Published: April 2020

Increase of photovoltaics (PV) penetration and concentration of electric vehicle (EV) charging may cause voltage violation in distribution lines. One measure for voltage violation in distribution lines is reactive power control. In this research, to reduce additional installation cost of reactive power control equipment, reactive power control by use of power factor correction converters in consumer loads was proposed. In this paper, voltage control ability of the proposed method was evaluated from the point of additional increase of PV generation and EV charging. Distribution voltage distortion caused by harmonic currents from consumer loads to which the proposed method were applied was also evaluated from the point of maximum reactive power output from loads within allowable voltage distortion level.
Pulmonary artery catheter use in acute myocardial infarction‐cardiogenic shock
Authors: Vallabhajosyula Saraschandra , Shankar Aditi , Patlolla Sri Harsha , Prasad Abhiram , Bell Malcolm R. , Jentzer Jacob C. , Arora Shilpkumar , Vallabhajosyula Saarwaani , Gersh Bernard J. , Jaffe Allan S. , Holmes David R. , Dunlay Shannon M. , Barsness Gregory W.
Published: April 2020

Aims

The aim of this study is to evaluate the contemporary use of a pulmonary artery catheter (PAC) in acute myocardial infarction‐cardiogenic shock (AMI‐CS).

Methods and results

A retrospective cohort of AMI‐CS admissions using the National Inpatient Sample (2000–2014) was identified. Admissions with concomitant cardiac surgery or non‐AMI aetiology for cardiogenic shock were excluded. The outcomes of interest were in‐hospital mortality, resource utilization, and temporal trends in cohorts with and without PAC use. In the non‐PAC cohort, the use and outcomes of right heart catheterization was evaluated. Multivariable regression and propensity matching was used to adjust for confounding. During 2000–2014, 364 001 admissions with AMI‐CS were included. PAC was used in 8.1% with a 75% decrease during over the study period (13.9% to 5.4%). Greater proportion of admissions to urban teaching hospitals received PACs (9.5%) compared with urban non‐teaching (7.1%) and rural hospitals (5.4%); P < 0.001. Younger age, male sex, white race, higher comorbidity, noncardiac organ failure, use of mechanical circulatory support, and noncardiac support were independent predictors of PAC use. The PAC cohort had higher in‐hospital mortality (adjusted odds ratio 1.07 [95% confidence interval 1.04–1.10]), longer length of stay (10.9 ± 10.9 vs. 8.2 ± 9.3 days), higher hospitalization costs ($128 247 ± 138 181 vs. $96 509 ± 116 060), and lesser discharges to home (36.3% vs. 46.4%) (all P < 0.001). In 6200 propensity‐matched pairs, in‐hospital mortality was comparable between the two cohorts (odds ratio 1.01 [95% confidence interval 0.94–1.08]). Right heart catheterization was used in 12.5% of non‐PAC admissions and was a marker of greater severity but did not indicate worse outcomes.

Conclusions

In AMI‐CS, there was a 75% decrease in PAC use between 2000 and 2014. Admissions receiving a PAC were a higher risk cohort with worse clinical outcomes.
Microvascular disease and heart failure with reduced and preserved ejection fraction in type 2 diabetes
Authors: Mordi Ify R. , Tee Aaron , Palmer Colin N. , McCrimmon Rory J. , Doney Alexander S.F. , Lang Chim C.
Published: April 2020

Aims

Identification of patients with type 2 diabetes (T2D) at increased risk of incident heart failure (HF) beyond traditional risk factors such as prior myocardial infarction (MI) might allow selection of patients who would benefit from preventative treatment. Microvascular disease (MiVD) is thought to play a pathophysiological role in the development of HF in T2D; however, its association with new‐onset HF with reduced or preserved ejection fraction has not been specifically defined.

Methods and results

Patients in the Genetics of Diabetes Audit and Research Tayside Scotland study were linked to echocardiography, prescriptions, and clinical outcomes. In total, 9141 patients with T2D were identified for analysis. Clinical variables and the presence of retinopathy, nephropathy, and neuropathy were assessed. Cumulative incidence was calculated for the association of both individual and the total number of MiVD states and incident HF. Median follow‐up was 9.3 years. In total, there were 900 HF events. The presence of any MiVD was independently associated with both HF with reduced ejection fraction (hazard ratio 1.40; 95% confidence interval 1.11–1.76, P = 0.004) and HF with preserved ejection fraction (hazard ratio 1.38; 95% confidence interval 1.10–1.72, P = 0.005), with a stepwise association between the number of MiVD states and risk of incident HF (P for trend <0.001). Similar associations were found in sensitivity analyses limited to patients without a prior MI, and using competing risks analysis.

Conclusions

Individuals with T2D and with MiVD are at risk of incident HF independent of a history of prior HF or MI. Patients with MiVD could benefit from screening for HF and individualized therapy with treatments that lower HF risk.
Minimal clinically important difference in quality of life scores for patients with heart failure and reduced ejection fraction
Authors: Butler Javed , Khan Muhammad Shahzeb , Mori Claudio , Filippatos Gerasimos S. , Ponikowski Piotr , Comin‐Colet Josep , Roubert Bernard , Spertus John A. , Anker Stefan D.
Published: April 2020

Aims

While the associations of health‐related quality of life scores in heart failure (HF) [e.g. the Kansas City Cardiomyopathy Questionnaire (KCCQ)] with clinical outcomes are well established, their interpretation in the context of what magnitudes of change are clinically important to patients is less clear. The main objective of this study was to correlate the changes in the KCCQ and Patient Global Assessment (PGA) in patients with HF with reduced ejection fraction (HFrEF) to determine minimal clinically important difference (MCID).

Methods and results

We analysed data from 459 patients of the FAIR‐HF trial. Both KCCQ and PGA were assessed at 4 and 24 weeks after enrolment. An anchor‐based approach was used to calculate MCID at week 4 and 24. PGA was chosen as the clinical anchor against which changes in the KCCQ scores were calibrated. For each category of change in PGA, the corresponding differences were calculated by the mean scores of various domains of KCCQ along with 95% confidence intervals (CIs). There was fair correlation between PGA and changes in overall summary scores (OSS) (r = 0.31; P < 0.001), clinical summary scores (CSS) (r = 0.36; P < 0.001) and physical limitation scores (PLS) (r = 0.31; P < 0.001) from baseline to week 4. KCCQ OSS, CSS and PLS MCID for ‘little improvement’ at week 4 were 3.6 (1.0–6.2), 4.5 (1.8–7.2) and 4.7 (1.4–8.0) points, respectively. OSS, CSS and PLS MCID for ‘little improvement’ at week 24 were 4.3 (0.2–8.4), 4.5 (0.5–8.5) and 4.0 (−0.9–9.0) points, respectively.

Conclusion

The MCID threshold for KCCQ score was generally consistent and numerically lower than the threshold of 5‐point change considered for clinical outcome prognosis and were stable between 4 and 24 weeks. This suggests that even changes smaller than the traditional 5‐point improvements in KCCQ may be clinically meaningful. Also, these results can aid in the clinical interpretation of patient‐reported outcomes, and better endpoint selection in future studies.
Ligand‐Assisted Electrochemical CO2 Reduction by Ru‐Polypyridyl Complexes
Authors: Ghosh Debashis , Kajiwara Takashi , Kitagawa Susumu , Tanaka Koji
Published: April 2020

The introduction of a simple triazole moiety on a terpyridine ligand in the complex [Ru(tpy)(bpy)(Cl)]+ ([1]+; tpy = 2,2':6',2''‐terpyridine; bpy = 2,2'‐bipyridine) gives rise to a suitable electrocatalyst for the reduction of CO2 to CO. The triazole group in [Ru(tpyaz)(bpy)(Cl)]+ {[2]+; tpyaz = 4'‐[4‐(tert‐butylphenyl)‐1H‐1,2,3‐triazol‐4‐yl]‐2,2':6',2''‐terpyridine} enables the complex [2]+ to bind with CO2 even at the one‐electron reduced state of the complex. Further 2nd‐electron addition after CO2‐coordination to the catalyst facilitates efficient CO2 reduction, based on cyclic voltammetry analysis.
Ligand Effects in Calcium Catalyzed Ketone Hydroboration
Authors: Brand Steffen , Causero Andrea , Elsen Holger , Pahl Jürgen , Langer Jens , Harder Sjoerd
Published: April 2020

The first “naked” (Lewis base‐free) cationic Ca amidinate complex [tBuAmDIPPCa(C6H6)]+[B(C6F5)4]– was prepared in 62 % yield {tBuAmDIPP = tBuC(N–DIPP)2; DIPP = 2,6‐diisopropylphenyl} by reaction of [tBuAmDIPPCaH]2 with [Ph3C]+[B(C6F5)4]– in chlorobenzene. The ether‐free complex tBuAmDIPPCaN(SiMe3)2 was obtained by removal of diethyl ether from its ether adduct. Crystal structures show that the amidinate ligand in both complexes is N,Aryl‐chelating. In this coordination mode the bulk of the amidinate ligand is comparable to that of a DIPP‐substituted β‐diketiminate ligand. Isomers with N,N‐coordinating amidinate ligands are circa 15 kcal/mol higher in energy and this coordination mode is only present in case additional ether ligands compensate for energy loss or in case of space limitation at the metal, e.g. in homoleptic (tBuAmDIPP)2Ca. A series of four Ca amidinate complexes, tBuAmDIPPCaX, were tested in the catalytic hydroboration of ketones and aldehydes by pinacolborane (HBpin). Catalytic activities increase for X– = I– < B(C6F5)4– < (Me3Si)2N– ≈ H–. For catalysts with unreactive anions, like I– or B(C6F5)4–, catalyst performance increases with the Lewis acidity of the metal and a mechanism is proposed in which HBpin and ketone coordinate to the Ca2+ ion which is followed by direct hydroboration. The more active catalysts with X– = (Me3Si)2N– or H– likely operate through a mechanism which involves intermediate metal hydride (or borate) complexes.
Modelling the behavior of inundated collapsible soils
Authors: Ashour Mohamed , Abbas Aser , Altahrany Ayman , Alaaeldin Ahmed
Published: April 2020

The properties of collapsible soil exhibit a lot of sensitivity toward the increase of water content, especially when the soil is close to the dry state. The inundation of collapsible soils induces a considerable drop in the void ratio (e) (ie, collapse potential, Cp, increase), which in return affects the dry unit weight (γd), friction angle (ϕ), and shear strength of the soil. The presented study employs large numbers of sandy and silty specimens of collapsible soils with different initial conditions (gathered from the literature) to develop a correlation that evaluates Cp of the soil (ie, settlement) due to inundation. The developed relationship accounts for the soil's initial properties such as the void ratio (e0), degree of saturation (Sr), and pressure applied to the inundated specimens. The presented model reflects the significant influence of Sr on Cp of inundated soil which considerably decreases by the increase of Sr. The determined properties of inundated collapsed soil, such as e and ϕ, are employed to construct the post‐inundation stress‐strain curve (ie, mobilized shear strength) of the soil based on the concepts of the conventional triaxial test. Comparisons between predicted and measured stress‐strain curves of inundated collapsible soils are presented for validation.
Numerical study and comparison of heat transferring ability of geometrically modified lithium‐ion cells for battery packs
Authors: Ranjan Upadhyay Mridul , Sachdeva Nishchay , Senthil Kumar Rajendran
Published: April 2020

The growth in electric vehicles is climbing so is the requirement of battery packs. Most commonly used battery packs are made of cylindrical lithium‐ion (Li‐ion) cells arranged a specific orientation. For a highly effective cooling system of a Li‐ion battery pack, an appropriate cell arrangement plays a substantial role. In electric vehicles, the battery pack decides the performance of it, as it is the only power source. Under extreme temperature conditions, the efficiency of the battery packs decreases. This non‐uniform effect must be minimized by recommending the appropriate location and orientations of cells. Hence, the battery pack is modeled and analyzed for both inline and staggered arrangements in this study. The numerical simulations are carried out using Ansys Fluent‐18. Moreover, this paper also explores the possibilities of using cells with an elliptical cross‐section and its effect on cooling performances and recommendations have been made. It is found that the pressure drop decreases by five times when the circle is replaced by an ellipse. The pressure drag decreases when the ellipse is placed in a staggered arrangement and is found to be 72.63% with respect to inline arrangements. Though the flow characteristics were in favor of the ellipse, the heat dissipation was found to be better for circular cells.
OIDPR: Optimized insulin dosage via privacy‐preserving reinforcement learning
Authors: Ying Zuobin , Zhang Yun , Cao Shuanglong , Xu Shengmin , Ma Maode
Published: April 2020

The precision of insulin dosage is essential in the process of diabetes treatment. The fact is providing precise dosage is almost impossible for clinicians since blood sugar levels are dynamically affected by many factors. Even though some auxiliary dosing systems have been proposed, the required real‐time physical data about the health situation of diabetics is still hard to synchronize to the end‐devices instantly. The traditional personalized drug delivery frameworks for accurate dosing of insulin always collect and transmit medical data in cleartext, which raises privacy problems. In this article, we propose a framework for an optimized insulin dosage via privacy‐preserving reinforcement learning to diabetics (OIDPR). In OIDPR, both the additive secret sharing and edge computing are deployed to achieve data confidentiality and performance optimization. The medical data is divided into multiple secret shares uniformly at random for outsourcing and operating at the edge servers. During the computation task of reinforcement learning, data is encrypted and processed via our proposed additive secret sharing protocol, where the privacy is reserved by the efficient encryption mechanism and the secret sharing system only incurs little workload. We provide comprehensive theoretical analyses and experimental results that demonstrate the supervisor functionality and high performance of our framework.
Mineralogical and geochemical changes due to hydrothermal alteration of the volcanic rocks at Acoculco geothermal system, Mexico
Authors: Pandarinath Kailasa , García‐Soto America Yosiris , Santoyo Edgar , Guevara Mirna , Gonzalez‐Partida Eduardo
Published: April 2020

Most of the volcanic rocks in the Acoculco geothermal system (AGS), near to the surface manifestations, are intensively altered. Thirty‐four surface volcanic rocks and five rocks from outcrop sections are considered in this work. Silica polymorphs (quartz, cristobalite and tridymite) are the dominant hydrothermal minerals in almost all the rock samples. The following other minerals are present in minor concentrations: alkali‐feldspars (sanidine potassic, anorthoclase and microcline), plagioclase feldspars (albite and anorthite), clay minerals (illite, kaolinite and montmorillonite), anhydrite, buddingtonite, titanoaugite, magnetite and anatase. This type of mineral assemblage of the rocks indicates an intensive silicic and argillic alteration. Comparison of the elemental concentrations of the surface acid rocks of the AGS with that of the precursor rock has indicated alteration‐induced changes in (a) chemical mobility in the concentrations of major element oxides, with an increase in the concentrations of SiO2, and TiO2, loss in those of Al2O3, Fe2O3, MnO, MgO, CaO, Na2O and K2O, and no statistically significant changes in those of P2O5, (b) no significant changes in the concentrations of LREE and MREE (except Dy and Ho), however, less but significant loss in the concentrations of Dy and Ho, and HREE, and (c) there is an enrichment in the concentrations of Nd, Sr, Sc, V, Nb, Ag, Sn, Pb, Tl, Ta, U and Th; and depletion in Be, Co, Zn, Ga, Ge, Rb, Y, Zr, Mo, Cs, Ba and Hf compared to those of the precursor rock. This type of distribution of the elements may indicate (a) an intense silicic alteration; and (b) REEs might have been leached from the original rocks because of hydrothermal alteration processes, but only LREEs, and MREEs (except Dy and Ho) can be redistributed and accommodated in the hydrothermal minerals, providing them with somewhat inert (immobile) behaviour. The mass change calculations have indicated that MnO and Sr have experienced the greatest and smallest mass changes, respectively. The identification of outliers in chemical data has revealed the presence of two distinctive groups of rocks. Ten out of the total 27 acid volcanic rocks with several elements as outlier data are negligibly to moderately altered (Group‐1), and the remaining 17 acid rocks without outlier data are intensively altered rocks (Group‐2).
Co‐occurrence of positive staff interactions and positive affect in memory‐care residents: An observational study
Authors: Fauth Elizabeth B. , Meyer Keirstin V. , Rose Cassidy
Published: April 2020

Objectives

With high numbers of persons with dementia living in residential care, it is vital to maximize psychosocial well‐being for this population in this setting. The current study observed whether proportions of positive affect in residents differed based on co‐occurring staff (typically certified nurse assistants) interaction types.

Methods

A trained research team observed staff/resident interactions and affect in residents with dementia in common areas of a residential memory care unit (n = 22; observations over one year, or 6999 minutes total).

Results

The most observed resident affect type was neutral (53.1% of all minutes observed), followed by positive affect (44.5%). The most common staff interaction type was neutral/no interaction (81.1% of all minutes observed), followed by positive staff interactions (18.1%). There was very little resident negative affect (2.4%) and staff negative interactions (.8%) observed. When staff had neutral/no/negative interactions, residents were positive 36% of the time, whereas when staff had positive interactions with them, residents were positive 81% of the time (z = 28.84, p < .001). A qualitative review of field notes identified themes and subthemes providing a more thorough understanding and context for the resident affect and staff interactions. While quantitative analyses suggested low rates of negative staff interaction, field notes highlight that neutral or no interactions with residents sometimes comprised missed opportunities, as well as more problematic lack of interaction (ignoring).

Conclusions

Not just avoiding negative interactions, but eliciting positive social interactions between staff and residents is important in promoting positive affect and overall wellbeing in persons with dementia.
Depth‐dependent abnormal cortical myelination in first‐episode treatment‐naïve schizophrenia
Authors: Wei Wei , Zhang Yamin , Li Yinfei , Meng Yajin , Li Mingli , Wang Qiang , Deng Wei , Ma Xiaohong , Palaniyappan Lena , Zhang Nanyin , Li Tao
Published: April 2020

Myelination is key to effective message passing in the central nervous system and is likely linked to the pathogenesis of schizophrenia (SZ). Emerging evidence indicates that a large portion of intracortical myelin insulates inhibitory interneurons that are highly relevant to pathogenesis of schizophrenia. Here for the first time, we characterized intracortical myelination across the entire cortical surface in first‐episode treatment‐naïve patients with schizophrenia (FES) using T1w/T2w ratio of structural MRI, FES patients exhibited significantly higher myelin content in the left inferior parietal lobe, supramarginal gyrus, and superior temporal gyrus in the superficial layer, as well as left IPL in the middle layer, but significantly lower myelin content in the left middle insula and posterior cingulate gyrus. Years of education, a proxy for onset of functional decline, significantly altered the relationship between abnormal parietal and posterior cingulate myelination and clinical symptoms, indicating that the pathoplastic role of myelination hinges on the age of onset of functional decline. In addition, higher myelination generally related to better cognitive function in younger subjects but worse cognitive function in older subjects. We conclude that FES is characterized by increased myelination of the superficial layers of the parietal–temporal association cortex, but reduced myelination of the cingulo‐insular midcortical layer cortex. Intracortical myelin content affects both cognitive functioning and symptom burden in FES, with the effect conditional upon age and timing of onset of functional decline. These results suggest myelination might be a critical biological target for procognitive interventions in SZ.
Gray matter volume and estimated brain age gap are not linked with sleep‐disordered breathing
Authors: Mohajer Bahram , Abbasi Nooshin , Mohammadi Esmaeil , Khazaie Habibolah , Osorio Ricardo S. , Rosenzweig Ivana , Eickhoff Claudia R. , Zarei Mojtaba , Tahmasian Masoud , Eickhoff Simon B. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: April 2020

Alzheimer's disease (AD) and sleep‐disordered breathing (SDB) are prevalent conditions with a rising burden. It is suggested that SDB may contribute to cognitive decline and advanced aging. Here, we assessed the link between self‐reported SDB and gray matter volume in patients with AD, mild cognitive impairment (MCI) and healthy controls (HCs). We further investigated whether SDB was associated with advanced brain aging. We included a total of 330 participants, divided based on self‐reported history of SDB, and matched across diagnoses for age, sex and presence of the Apolipoprotein E4 allele, from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Gray‐matter volume was measured using voxel‐wise morphometry and group differences in terms of SDB, cognitive status, and their interaction were assessed. Further, using an age‐prediction model fitted on gray‐matter data of external datasets, we predicted study participants' age from their structural images. Cognitive decline and advanced age were associated with lower gray matter volume in various regions, particularly in the bilateral temporal lobes. Brains age was well predicted from the morphological data in HCs and, as expected, elevated in MCI and particularly in AD subjects. However, there was neither a significant difference between regional gray matter volume in any diagnostic group related to the SDB status, nor in SDB‐by‐cognitive status interaction. Moreover, we found no difference in estimated chronological age gap related to SDB, or by‐cognitive status interaction. Contrary to our hypothesis, we were not able to find a general or a diagnostic‐dependent association of SDB with either gray‐matter volumetric or brain aging.
Comparative Preliminary Evaluation of 2 In-stream Water Treatment Technologies for the Agricultural Reuse of Drainage Water in the Nile Delta
Authors: Pinelli Davide , Zanaroli Giulio , Rashed Ahmed Ali , Oertlé Emmanuel , Wardenaar Tjerk , Mancini Maurizio , Vettore Dario , Fiorentino Carmine , Frascari Dario
Published: April 2020

In the Nile Delta, a complex network of canals collects drainage water from surface-irrigated fields but also from municipal wastewater. The goal of this work was to assess the technical, environmental, and financial feasibility of the upgrade of a drainage canal (DC) into either an in-stream constructed wetland (ICW) or a canalized facultative lagoon (CFL), in order to produce a water reusable in agriculture according to Egyptian law. The model-based design of the proposed technologies was derived from field experimental data for the ICW and laboratory data for the CFL. Both technologies, integrated by a sedimentation pond and a disinfection canal, led to the attainment of the water quality standards imposed by Egyptian Law 92/2013 for the reuse of drainage water. The life cycle assessment indicated that the upgrade of an existing DC to either an ICW or a CFL results in an extremely small environmental burden, ≤0.3% of that of a traditional activated sludge process. The cost–benefit analysis (CBA) was based on the assumptions that 1) farmers currently irrigate a nonfood crop (cotton) with the low-quality drainage water present in the DC, and 2) thanks to the upgrade to a ICW or CFL, farmers will irrigate a food crop characterized by a higher market price (rice). The CBA indicated that the DC upgrade to an ICW represents an attractive investment because it leads to a financial rate of return >10% over a wide range of cotton market prices. Conversely, the upgrade to a CFL is less attractive due to high investment costs. In conclusion, the upgrade of DCs to ICWs appears a promising option for the treatment of drainage canal water in the Nile Delta, thanks to the high pollutant removal performances, low cost, and negligible environmental burden. Integr Environ Assess Manag 2020;16:920–933. © 2020 SETAC
Allergen‐specific subcutaneous immunotherapy for Japanese cedar pollinosis decreases the number of metachromatic cells and eosinophils in nasal swabs during the preseason and in season
Authors: Otsuka Kuninori , Otsuka Hirokuni , Matsune Shoji , Okubo Kimihiro
Published: April 2020

Background and objective

Nasal symptoms of allergic rhinitis can be reduced with allergen‐specific subcutaneous immunotherapy (SCIT). However, the mechanisms underlying the effectiveness of SCIT for Japanese cedar pollinosis are not well understood. We studied changes in the numbers of metachromatic cells, eosinophils and neutrophils in nasal swabs following SCIT for Japanese cedar pollinosis.

Methods

Subjects were either untreated or given SCIT for 0.5 to 13 years duration. For the 2019 seasons, nasal swabs were taken in the pollinosis preseason (immunotherapy n = 36; untreated control, n = 62) and in the pollinosis season (immunotherapy n = 45; untreated control n = 46) and the numbers of mast cells, eosinophils and neutrophils assessed by microscopy.

Results

There were significant improvements in symptom severities following SCIT in comparison to untreated subjects (P < .0003, the Mann‐Whitney U test) in preseason, and (P < .00001) in season. Metachromatic cell counts from nasal swabs of SCIT subjects in preseason and in the season were lower than those of untreated subjects (P = .0029 and P = .031, respectively). Eosinophil numbers in nasal swabs of subjects given SCIT were lower than in untreated subjects (P = .0031) in season, but not in preseason. There were no significant differences in degrees of neutrophilia between untreated and SCIT subjects in preseason and in season.

Conclusion

One mechanism underlying the effectiveness of SCIT for Japanese cedar pollinosis involves a reduction in the number of metachromatic cells in nasal swabs in the preseason and an inhibition of increases in the number of metachromatic cells and eosinophils in season.
Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO‐grade II—Report from the German/Swiss SIOP‐LGG 2004 cohort
Authors: Falkenstein Fabian , Gessi Marco , Kandels Daniela , Ng Ho‐Keung , Schmidt René , Warmuth‐Metz Monika , Bison Brigitte , Krauss Juergen , Kortmann Rolf‐Dieter , Timmermann Beate , Thomale Ulrich‐Wilhelm , Albert Michael H. , Pekrun Arnulf , Maaß Eberhard , Gnekow Astrid K. , Pietsch Torsten
Published: April 2020

Reports on pediatric low‐grade diffuse glioma WHO‐grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2‐entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub‐entities proved unfavorable for survival. Within the prospectively registered, population‐based German/Swiss SIOP‐LGG 2004 cohort 100 patients (age 0.8‐17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event‐free survival dropped to 0.44, while 5 years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3‐K27M‐mutation in 4, IDH1‐mutation in 11, BRAF‐V600‐mutation in 12, KIAA1549‐BRAF‐fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8 years, except for tumors carrying KIAA1549‐BRAF‐fusions. Histone3‐K27M‐mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2‐entities, with the exemption of Histone3‐K27M‐mutant tumors that require a HGG‐related treatment strategy. Our data confirm the importance to genetically define pediatric low‐grade diffuse gliomas for proper treatment decisions and risk assessment.
Enhanced new bone formation in canine maxilla by a graft of electrically polarized β‐tricalcium phosphate
Authors: Nohara Kohei , Itoh Soichiro , Akizuki Tatsuya , Nakamura Miho , Fukuba Shunsuke , Matsuura Takanori , Okada Munehiro , Izumi Yuichi , Iwata Takanori , Yamashita Kimihiro
Published: April 2020

We succeeded in the electrical polarization of β‐tricalcium phosphate (β‐TCP) granules and performed an unprecedented attempt to implant them into maxillary bone defects in canines to confirm their ability to facilitate new bone formation. Two holes were drilled into each maxilla half of a canine and filled with electrically polarized and nonpolarized β‐TCP granules (grouping assignment was decided randomly). The implanted specimens were dissected en bloc and used for microcomputed tomography (μCT) observations and histological analyses 4 and 8 weeks after the operation. New bone ingrowth in the bone hole progressed over time from the superficial layer of the cortex toward the inner cancellous bone. The percentage area of new bone in the bone hole, as measured by μCT in the sagittal plane, was significantly larger after 4 and 8 weeks, and that measured by H&E‐stained specimens in the transverse plane after 4 weeks was significantly larger in the polarized group than in the nonpolarized group. In addition to the structural stability and chemical characteristics of the β‐TCP granules, electrical stimulation bears influence not indirectly but directly on osteogenic and vessel cells, which might work cooperatively for the early initiation of the bone formation process.
Protein spectrum changes in exosomes after therapeutic plasma exchange in patients with neuromyelitis optica
Authors: Ma Chunya , Wang Shufang , Wang Guibin , Wu Ying , Yang Tianxin , Shen Wanjun , Zhuang Yuan , Zhang Leiying , Liu Xiaomin , Yang Lu , Feng Yannan , Yu Yang , Liu Zhong , Wang Deqing
Published: April 2020

Introduction

Neuromyelitis optica (NMO) is an autoimmune disease with a high rate of blindness and positive for the detection of aquaporin‐4 antibody (AQP4) in most patients. NMO acute attacks are managed by high‐doses of intravenous methylprednisolone followed by oral taper, and if symptoms fail to resolve, therapeutic plasma exchange (TPE) is added. TPE can remove pathological antibodies and inflammatory factors leading to clinical improvement.

Methods

A total of 40 TPE fluid collections from the first to fifth TPE treatments were obtained from eight patients. Exosomes were isolated by ultracentrifugation. Mass spectrometry analyses were used to compare protein change in TPE fluid collection exosomes after the first to the fifth TPE treatments in these patients.

Results

We detected 647 exosome proteins through data‐independent acquisition analysis. It was found that some unknown functional antibody fragments and complement pathway proteins decreased after TPE treatment. The results revealed a significant involvement of the following two key pathways: the primary immunodeficiency and systemic lupus erythematosus that may be associated with NMO pathophysiology and TPE treatment efficacy (P < .05). A series of complement proteins may contribute to NMO; in addition, the following proteins increased with plasma exchange: complement factor H‐related protein 5, bridging integrator 2, neuroplastin, pigment epithelium‐derived factor, ficolin‐1, extracellular matrix protein 1, and fatty acid‐binding protein 5.

Conclusion

Our study may provide a new perspective on the pathogenesis and treatment efficacy of NMO.
MicroRNA‐33b regulates hepatocellular carcinoma cell proliferation, apoptosis, and mobility via targeting Fli‐1‐mediated Notch1 pathway
Authors: Wang Huiling , Lin Xingtao , Liu Entao , Jian Zhixiang , Ou Yingliang
Published: April 2020

MicroRNAs (miRNAs) have been confirmed to play pivotal roles in hepatocellular carcinoma (HCC) carcinogenesis. However, the underlying function of microRNA‐33b (miR‐33b) in HCC remains unclear. Here, we found that miR‐33b level was significantly reduced in both HCC tissues and tumor cell lines. Further, luciferase reporter assay and western blot analysis confirmed that Friend leukemia virus integration 1 (Fli‐1) was a direct target of miR‐33b. Overexpression of miR‐33b dramatically suppressed HCC tumor cell proliferation and cell mobility, but facilitated tumor cell apoptosis in vitro. Besides, restoration of Fli‐1 partially attenuated miR‐33b‐mediated inhibition of cell growth and metastasis via activating Notch1 signaling and its downstream effectors. Our findings demonstrate the important role of miR‐33b/Fli‐1 axis in HCC progression and provide novel therapeutic candidates for HCC clinical treatment.