bluuebunny/crossref_metadata_2025 huggingface dataset:
QSAR studies on benzothiophene derivatives as Plasmodium falciparum N‐myristoyltransferase inhibitors: Molecular insights into affinity and selectivity
Authors: Garcia Mariana L. , de Oliveira Andrew A. , Bueno Renata V. , Nogueira Victor H. R. , de Souza Guilherme E. , Guido Rafael V. C.
Published: February 2020

Malaria is an infectious disease caused by protozoan parasites of the genus Plasmodium and transmitted by Anopheles spp. mosquitos. Due to the emerging resistance to currently available drugs, great efforts must be invested in discovering new molecular targets and drugs. N‐myristoyltransferase (NMT) is an essential enzyme to parasites and has been validated as a chemically tractable target for the discovery of new drug candidates against malaria. In this work, 2D and 3D quantitative structure–activity relationship (QSAR) studies were conducted on a series of benzothiophene derivatives as P. falciparum NMT (PfNMT) and human NMT (HsNMT) inhibitors to shed light on the molecular requirements for inhibitor affinity and selectivity. A combination of Quantitative Structure–activity Relationship (QSAR) methods, including the hologram quantitative structure–activity relationship (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) models, were used, and the impacts of the molecular alignment strategies (maximum common substructure and flexible ligand alignment) and atomic partial charge methods (Gasteiger‐Hückel, MMFF94, AM1‐BCC, CHELPG, and Mulliken) on the quality and reliability of the models were assessed. The best models exhibited internal consistency and could reasonably predict the inhibitory activity against both PfNMT (HQSAR: q2/r2/r2pred = 0.83/0.98/0.81; CoMFA: q2/r2/r2pred = 0.78/0.97/0.86; CoMSIA: q2/r2/r2pred = 0.74/0.95/0.82) and HsNMT (HQSAR: q2/r2/r2pred = 0.79/0.93/0.74; CoMFA: q2/r2/r2pred = 0.82/0.98/0.60; CoMSIA: q2/r2/r2pred = 0.62/0.95/0.56). The results enabled the identification of the polar interactions (electrostatic and hydrogen‐bonding properties) as the major molecular features that affected the inhibitory activity and selectivity. These findings should be useful for the design of PfNMT inhibitors with high affinities and selectivities as antimalarial lead candidates.
Adding vitamin D3 to the dipeptidyl peptidase‐4 inhibitor saxagliptin has the potential to protect β‐cell function in LADA patients: A 1‐year pilot study
Authors: Zhang Ziwei , Yan Xiang , Wu Chao , Pei Xieyi , Li Xia , Wang Xiangbing , Niu Xiaohong , Jiang Hongwei , Zeng Xiaomin , Zhou Zhiguang
Published: February 2020

Aims

This trial was conducted to explore the protective effect on β‐cell function of adding vitamin D3 to DPP‐4 inhibitors to treat patients with latent autoimmune diabetes in adults (LADA).

Methods

60 LADA patients were randomized to group A (n = 21) ‐ conventional therapy with metformin (1‐1.7 g/day) and/or insulin treatment; group B (n = 20) ‐ saxagliptin (5 mg/day) plus conventional therapy; and group C (n = 19) ‐ vitamin D3 (2000 IU/day) plus saxagliptin and conventional therapy for 12 months. Fasting and 2‐hour postprandial blood samples were collected to measure blood glucose, glycosylated hemoglobin and C‐peptide levels at baseline and after 3, 6 and 12 months of treatment.

Results

During the 12 months of follow‐up, the levels of fasting C‐peptide (FCP), 2‐hour postprandial C‐peptide (PCP) and the C‐peptide index (CPI, serum C‐peptide‐to‐plasma glucose level ratio) were maintained in group C. In contrast to those in group A and group B, FCP levels decreased significantly in group B, and CPI levels declined significantly in group A during the 1‐year treatment (P < .05). Additionally, the levels of GADA titers in group C significantly decreased compared with those at baseline (P < .05), but no significant differences in GADA titers levels were detected in group A and group B. No significant differences were found among the three groups in the levels of FCP, PCP, the CPI or GADA titers.

Conclusions

The data suggested that adding 2000 IU/day vitamin D3 to saxagliptin might preserve β‐cell function in patients with LADA.
Integrating broad‐scale data to assess demographic and climatic contributions to population change in a declining songbird
Authors: Saracco James F. , Rubenstein Madeleine
Published: February 2020

Climate variation and trends affect species distribution and abundance across large spatial extents. However, most studies that predict species response to climate are implemented at small spatial scales or are based on occurrence‐environment relationships that lack mechanistic detail. Here, we develop an integrated population model (IPM) for multi‐site count and capture‐recapture data for a declining migratory songbird, Wilson's warbler (Cardellina pusilla), in three genetically distinct breeding populations in western North America. We include climate covariates of vital rates, including spring temperatures on the breeding grounds, drought on the wintering range in northwest Mexico, and wind conditions during spring migration. Spring temperatures were positively related to productivity in Sierra Nevada and Pacific Northwest genetic groups, and annual changes in productivity were important predictors of changes in growth rate in these populations. Drought condition on the wintering grounds was a strong predictor of adult survival for coastal California and Sierra Nevada populations; however, adult survival played a relatively minor role in explaining annual variation in population change. A latent parameter representing a mixture of first‐year survival and immigration was the largest contributor to variation in population change; however, this parameter was estimated imprecisely, and its importance likely reflects, in part, differences in spatio‐temporal distribution of samples between count and capture‐recapture data sets. Our modeling approach represents a novel and flexible framework for linking broad‐scale multi‐site monitoring data sets. Our results highlight both the potential of the approach for extension to additional species and systems, as well as needs for additional data and/or model development.
Evolutionary rate variation among genes involved in galactomannan biosynthesis in Coffea canephora
Authors: Ogutu Collins , Cherono Sylvia , Ntini Charmaine , Mollah Mohammad Dulal , Zhao Lei , Belal Mohammad A. , Han Yuepeng
Published: February 2020

The endosperm cell walls of mature coffee seeds accumulate large amounts of mannan storage polysaccharides, which serve as nutrient reserve for embryo and contribute to beverage quality. Our study investigated the evolutionary patterns of key galactomannan (GM) biosynthesis genes using dN/dS ratio, synteny, and phylogenetic analysis and detected heterogeneity in rate of evolution among gene copies. Selection ratio index revealed evidence of positive selection in the branch editing gene Coffea canephora alpha (α) galactosidase (Cc‐alpha Gal) at Cc11_g15950 copy (ω = 1.12), whereas strong purifying selection on deleterious mutations was observed in the Coffea canephora uridine diphosphate (UDP)‐glucose 4′‐epimerase (Cc‐UG4E) and Coffea canephora mannose‐1P guanylytransferase (Cc‐MGT) genes controlling the crucial nucleotide carbon sugar building blocks flux in the pathway. Relatively low sequence diversity and strong syntenic linkages were detected in all GM pathway genes except in Cc‐alpha Gal, which suggests a correlation between selection pressure and nucleotide diversity or synteny analysis. In addition, phylogenetic analysis revealed independent evolution or expansion of GM pathway genes in different plant species, with no obvious inferable clustering patterns according to either gene family or congruent with evolutionary plants lineages tested due to high dynamic nature and specific biochemical cell wall modification requirements. Altogether, our study shows a significant high rate of evolutionary variation among GM pathway genes in the diploid C. canephora and demonstrates the inherent variation in evolution of gene copies and their potential role in understanding selection rates in a homogenously connected metabolic pathway.
C‐H Functionalization of Biaryl Compounds
Authors: Wang Ju , Liu Chen‐Fu , Zheng Quan , Rao Guo‐Wu
Published: February 2020

In recent years, C–C, C–N, and C–O bonds constructed by C–H functionalization have reached considerable attention due to excellent functional group tolerance, cost‐effectiveness, and atom‐economy. Biaryl compounds are one of the important skeletons in the field of organic chemistry, and have been extensively applied to pharmaceuticals, functional materials, and agrochemicals. However, there have been far fewer reports on C–H functionalization by employing biaryls as substrates. Herein we comprehensively review the C–H functionalization of biaryls including annulation/substitution reactions. The discussion is subdivided according to specific reaction types. In summary, we analyzed the corresponding reaction from the points of view of conditions, directing groups, mechanism, and applications. We hope that this minireview will be beneficial for more synthetic chemists to grasp the design of C–H functionalization of biaryl compounds and enlighten them with more ideas on this issue.
Quantitative Mono‐Formation and Crystallographic Characterization of Pyrazole‐ and Pyrrole‐Ring Fused Derivatives of C60
Authors: Yang Le , Shen Wangqiang , Liu Yangchun , Hao Debo , Pan Changwang , Yu Bing , Cong Hailin , Jin Peng , Lu Xing
Published: February 2020

Nitrogen‐heterocyclic fullerene derivatives have received great interest in the past years due to their potential biological activities and optical properties. Herein, we report a quantitative mono‐formation of the pyrazole‐ and pyrrole‐ring fused derivatives of fullerene C60, i.e., C60 (C13N2H10) (3) and C60 (C9NH11) (4), from the respective reactions between C60 and diphenylnitrilimine (1) and N‐benzylazomethine ylide (2). Single‐crystal X‐ray diffraction (XRD) crystallographic results unambiguously confirm the formation of [6,6]‐closed derivatives (3 and 4). Interestingly, the intermolecular π–π interactions between the phenyl groups and C60 spheres are observed in the crystal of 3, but they are absent from 4, indicating that the number of the external phenyl groups has an important influence on the stacking pattern of derivatives during crystallization. Electrochemical results show that the reduction potentials of 3 are positively shifted compared with the corresponding values of pristine C60, while the reduction potentials of 4 are all cathodically shifted, revealing the redox processes of C60 can be selectively modulated by changing the structures of the addends. Notably, our theoretical results demonstrate that the quantitative formation of merely one mono‐adduct without any bis‐ or multi‐adducts detected in both reactions is a direct result from the steric hindrance of the existing bulky pyrazole‐ or pyrrole‐ring moiety on the C60 cage. This work thus presents a quantitative way for the mono‐formation of the pyrrole‐ and pyrazole‐ring fused derivatives of C60, which are potentially useful as organic photovoltaic devices and biological reagents.
Company's retention needs lead to university's enrollment boost
Authors: Sutton Halley
Published: February 2020

CHICAGO — A few years ago, supervisors at FedEx realized they had a retention problem. For employees who worked at the company, turnover was about 92%. For the Memphis warehouse, which employed about 12,000 people, that meant replacing approximately 10,000 employees annually. “It cost them about $3,500 to train a new employee,” said Courtney Brafford, Coordinator of Student Success Initiatives and Retention Specialist at the University of Memphis. As an initiative to retain employees and build lasting skills, FedEx partnered with UM to develop online pathways to degrees available to employees with no upfront tuition cost.
In pursuing international applicants, keep goals aligned with larger mission
Authors: Enos Gary
Published: February 2020

As Santa Clara University manages slow but steady growth in its population of international students, its leaders focus on making sure its strategic goals remain aligned with the university's values‐driven culture as a Jesuit institution. “Know thyself” is the first piece of advice Director of International Admission Becky Konowicz would share with colleagues at any other institution as they explore their own objectives in attracting and retaining international students.
Tackle major changes by engaging all stakeholders, sharing roadmap to the goal
Authors: Gelpi Aileen
Published: February 2020

Annamarie Bianco is no stranger to high‐level, high‐stress positions. Before joining Georgetown University in the position of Associate Vice President and University Registrar in 2016, she was Registrar for almost nine years at the City University of New York, where she was responsible for implementing universitywide policies and serving as a resource for 24 college registrars throughout the university system.
Cu/Cu2O Nanoparticle–Decorated MoO2 Nanoflowers as a Highly Efficient Electrocatalyst for Hydrogen Evolution Reaction
Authors: Tong Jing , Xue Yanan , Wang Jianzhi , Wang Miao , Chen Weimin , Tian Qifeng , Yu Faquan
Published: February 2020

The development of highly efficient, economical, and sustainable electrocatalysts based on non‐noble metals for hydrogen evolution reaction (HER) is of vital significance for large‐scale renewable energy storage. Herein, an effective synthetic strategy for the construction of MoO2 nanoflowers decorated with metallic Cu/Cu2O nanoparticles (NPs) on Ni foam (NF) (Cu2O/MoO2@Cu/NF) with a simple two‐step method is reported. The prepared Cu2O/MoO2@Cu/NF as an electrocatalyst exhibits outstanding reactivity and remarkable stability in alkaline solution. The onset overpotential of Cu2O/MoO2@Cu/NF approaches 0 V. An overpotential as low as 32 mV is obtained to afford a current density of 10 mA cm−2, comparable with Pt/C catalysts. The Tafel slope is low at 40 mV dec−1 as well. The involvement of zero‐valent Cu greatly reduces the resistance. The well‐dispersed Cu/Cu2O NPs on the sphere‐like MoO2 nanoflowers exaggerate the surface area. The ringent channels provide the fast release of evolved bubbles. Furthermore, the enhanced conductivity and large surface area lead to significant activity in HER. Herein, a novel design and facile synthesis of a highly efficient electrocatalyst with catalytic activity that is comparable to a Pt/C catalyst is provided.
Rheological analysis of Newtonian and non‐Newtonian fluids using Marsh funnel: Experimental study and computational fluid dynamics modeling
Authors: Li Zhaochuan , Zheng Lihui , Huang Weian
Published: February 2020

In the drilling industry, Marsh funnel viscosity is only a dynamic viscosity and cannot characterize actual rheology. Thus, measuring rheology using a Marsh funnel has been drawing considerable attention. In this study, we develop simplified mathematical models for wall shear rate, wall shear stress, and their consistency plots. Moreover, we propose mathematical models for the rheological parameters of Newtonian and non‐Newtonian fluids. We compare the results of the present model with those of a ZNN‐6 viscometer, a computational fluid dynamics (CFD) model, and other analytical models. According to the quantitative analysis results, the average systematic error of the Newtonian, apparent, and plastic viscosities between the present model and the ZNN‐6 viscometer measurements is 1.35%, 8.18%, and 5.42%, respectively. The average systematic error of the yield stress is 21.43%, which is under the controllable scope. Meanwhile, results of the qualitative analysis reveal that the present model for the wall shear rate and stress agrees with the CFD model. Moreover, the flow field inside the Marsh funnel is axisymmetric and has a component velocity in the horizontal direction. In summary, the proposed model is accurate, concise, available for field applications, and beneficial for a successful and safe drilling operation. Furthermore, the CFD approach is a necessary complement to exploring the actual field flow inside the Marsh funnel.
Evolution and application of airflow permeability characteristics of gob in roof cutting and pressure releasing mining method
Authors: Chen Xiangjun , Du Yunfei , Wang Liang , Zhao San
Published: February 2020

Cutting roof and release pressure technology has changed the pressure transmission mode of the roof and the caving characteristics of roof rock, which in turn has changed the permeability evolution of the gob. To obtain the permeability characteristics of the gob for the roof cutting and pressure releasing mining method, a mathematical model for the gob voidage and permeability was established by analyzing the overlying strata movement law and the lateral stress variation in the gob. The airflow migration law of haulage roadway 12 201 in Halagou coal mine was studied using Fluent software and an established mathematical model. The main conclusions obtained are as follows: The overburden pressure and lateral stress in the gob gradually increase with the advancement of the working face; along the direction of the retaining roadway, there are two roadway windflows entering the critical zones (the 22‐100 m and 390‐398 m sections). The inflow at these two sections accounted for 59% of the total air inflow, of which the most critical is the 28‐53 m section, which accounts for 43% of the total air inflow in the two severe air leakage sections. The findings of this work provide a theoretical basis for the implementation of antileakage technology in the gob under the roof cutting and pressure releasing mining method and help reduce the risk of spontaneous combustion in the gob.
Acute and Chronic Toxicity of Nickel and Zinc to a Laboratory Cultured Mayfly (Neocloeon triangulifer) in Aqueous but Fed Exposures
Authors: Soucek David J. , Dickinson Amy , Schlekat Chris , Van Genderen Eric , Hammer Edward J.
Published: February 2020

Aquatic insects are poorly represented in water quality criteria, and previous studies have suggested a lack of sensitivity in acute toxicity tests despite observational studies demonstrating the contrary. Our objectives were to determine the toxicity of nickel (Ni) and zinc (Zn) to the mayfly Neocloeon triangulifer in fed acute (96-h) and chronic exposures to estimate aqueous effect concentrations while acknowledging the importance of dietary exposure for these insects. For the chronic tests, we conducted preliminary full–life cycle (~25–30 d) and subchronic (14 d) exposures to compare the relative sensitivity of the 2 test durations under similar conditions (i.e., feeding rates). Observing similar sensitivity, we settled on 14 d as the definitive test duration. Furthermore, we conducted experiments to determine how much food could be added to a given volume of water while minimally impacting dissolved metal recovery; a ratio of food dry mass to water volume (<0.005) achieved this. In the 14-d tests, we obtained a median lethal concentration and most sensitive chronic endpoint of 147 and 23 µg/L dissolved Ni (acute to chronic ratio [ACR] = 6.4), respectively, and 81 (mean value) and 10 µg/L dissolved Zn (ACR = 8.1), respectively. The acute values are orders of magnitude lower than previously published values for mayflies, probably most importantly due to the presence of dietary exposure but also potentially with some influence of organism age and test temperature. Environ Toxicol Chem 2020;39:1196–1206. © 2020 SETAC
Incorporating external information to improve sparse signal detection in rare‐variant gene‐set‐based analyses
Authors: Zhang Mengqi , Gelfman Sahar , McCarthy Janice , Harms Matthew B. , Moreno Cristiane A.M. , Goldstein David B. , Allen Andrew S.
Published: February 2020

Gene‐set analyses are used to assess whether there is any evidence of association with disease among a set of biologically related genes. Such an analysis typically treats all genes within the sets similarly, even though there is substantial, external, information concerning the likely importance of each gene within each set. For example, for traits that are under purifying selection, we would expect genes showing extensive genic constraint to be more likely to be trait associated than unconstrained genes. Here we improve gene‐set analyses by incorporating such external information into a higher‐criticism‐based signal detection analysis. We show that when this external information is predictive of whether a gene is associated with disease, our approach can lead to a significant increase in power. Further, our approach is particularly powerful when the signal is sparse, that is when only a small number of genes within the set are associated with the trait. We illustrate our approach with a gene‐set analysis of amyotrophic lateral sclerosis (ALS) and implicate a number of gene‐sets containing SOD1 and NEK1 as well as showing enrichment of small p values for gene‐sets containing known ALS genes. We implement our approach in the R package wHC.
Messtechnische Begleitung der Einbringung einer Tragbohle mittels Vibration und Schlagrammung
Authors: Beuße Jannik , Grabe Jürgen
Published: February 2020

Die lagegetreue Installation kombinierter Stahlspundwände ist weiterhin eine Herausforderung. Deformierte oder von ihrer geplanten Lage abweichende Tragbohlen können zu einem Systemversagen führen. Es gibt nur vereinzelt Empfehlungen, wie das Einbringgerät und die Rammführung passend zum Boden und der einzubringenden Tragbohle zu wählen ist. Zusätzlich wird der Nachweis für kombinierte Wände nur für den Endzustand erbracht, obwohl das Tragverhalten durch den Installationsprozess beeinflusst wird, sodass Richtlinien für die Auswahl einer zielführenden Rammkonfiguration sowie ein Nachweisverfahren unter Berücksichtigung der Einflüsse aus dem Einbringverfahren benötigt werden. Um die Dynamik des Installationsprozesses von Tragbohlen genauer zu untersuchen, wird die Einbringung einer Tragbohle mittels Vibration und Schlagrammung im Rostocker Hafen untersucht. Dabei werden die Beschleunigungen, Dehnungen und Neigungen an der Tragbohle gemessen. Zusätzlich werden die Beschleunigungen an der Rammführung und am Einbringgerät gemessen, um deren Einfluss auf das Bewegungsverhalten der Tragbohle zu untersuchen. Die resultierende Verformung und die Lage der Tragbohle im Endzustand kann ermittelt werden.
Geochronology, geochemistry, and Hf isotopes of mafic rocks from Dalabute ophiolitic mélange in West Junggar, Xinjiang (NW China): Implications for the magmatic source and tectonic setting
Authors: Li Hai , Li Yongjun , Yang Gaoxue , Wang Zuopeng , Ren Pengfei , Chang Haoying
Published: February 2020

Several Palaeozoic ophiolitic mélanges distributed in the West Junggar, Xinjiang, are remnants of the Paleo‐Asian Ocean evolution. They are important keys for studying the component, tectonic evolution, and crust–mantle interaction of the Central Asian Orogenic Belt (CAOB). This paper presents petrology, zircon U‐Pb chronology, geochemistry, and Hf isotope data of mafic rocks from the Dalabute ophiolitic mélange, West Junggar. The zircon U‐Pb chronology data of gabbro in the Dalabute ophiolitic mélange can be divided into two groups. The first group magmatic zircons yield a weighted mean age of 389.7 ± 7.7 Ma. It suggests that gabbros of the Dalabute ophiolitic mélange were formed during the period of Early‐middle Devonian, which represents the main period that the Dalabute back‐arc ocean basin expanded. The second group inherited zircons with ages ranging from 910 to 975 Ma were interpreted as Neoproterozoic materials of basement entered its magmatic source. Geochemical characteristics show that the mafic rocks from the Dalabute ophiolitic mélange can be subdivided into alkaline and tholeiite series. Whole‐rock and Hf isotopic data indicate that alkaline basalts have the signatures of typical OIB and formed in the oceanic island or seamount settings related to mantle plume, which were most likely derived from an enriched mantle source. Besides, tholeiitic rocks exhibit the features of MORB and generated in an immature back‐arc basin in the supra‐subduction zone. Their magmas originated from a depleted mantle that had been metasomatized by subduction‐related fluids and contaminated by materials with crustal nature. Therefore, Dalabute ophiolites are supposed to be generated from a back‐arc oceanic basin, which is relate to intra‐subduction and with mantle plumes developed within it. These results jointly provide convincing evidence for the evolution and property of the Dalabute ophiolite in the West Junggar and further supply reference and base for reconstruct the evolutionary history of the CAOB.
Changes in the transcriptional fingerprint of satellite glial cells following peripheral nerve injury
Authors: Jager Sara E. , Pallesen Lone T. , Richner Mette , Harley Peter , Hore Zoe , McMahon Stephen , Denk Franziska , Vægter Christian B.
Published: February 2020

Satellite glial cells (SGCs) are homeostatic cells enveloping the somata of peripheral sensory and autonomic neurons. A wide variety of neuronal stressors trigger activation of SGCs, contributing to, for example, neuropathic pain through modulation of neuronal activity. However, compared to neurons and other glial cells of the nervous system, SGCs have received modest scientific attention and very little is known about SGC biology, possibly due to the experimental challenges associated with studying them in vivo and in vitro. Utilizing a recently developed method to obtain SGC RNA from dorsal root ganglia (DRG), we took a systematic approach to characterize the SGC transcriptional fingerprint by using next‐generation sequencing and, for the first time, obtain an overview of the SGC injury response. Our RNA sequencing data are easily accessible in supporting information in Excel format. They reveal that SGCs are enriched in genes related to the immune system and cell‐to‐cell communication. Analysis of SGC transcriptional changes in a nerve injury‐paradigm reveal a differential response at 3 days versus 14 days postinjury, suggesting dynamic modulation of SGC function over time. Significant downregulation of several genes linked to cholesterol synthesis was observed at both time points. In contrast, regulation of gene clusters linked to the immune system (MHC protein complex and leukocyte migration) was mainly observed after 14 days. Finally, we demonstrate that, after nerve injury, macrophages are in closer physical proximity to both small and large DRG neurons, and that previously reported injury‐induced proliferation of SGCs may, in fact, be proliferating macrophages.
Late life education and cognitive function in older adults
Authors: Peeters Geeske , Kenny Rose Anne , Lawlor Brian
Published: February 2020

Objective

The potential role of education attained after the age of 50, for example, vocational training or recreational courses, in cognitive reserve has been unexplored. We examined the cross‐sectional and prospective associations between late life education (LLE) and global cognitive function in older adults.

Methods

A total of 5306 participants (50+ years) in The Irish Longitudinal Study of Ageing answered questions about highest level of education completed and LLE (2010). Cognitive function was defined as the number of errors on the Montreal cognitive assessment (MoCA) assessed in 2010 and 2014. The association between LLE and MoCA‐errors was examined using Poisson regression stratified by level of education. Sensitivity analyses were done to examine reverse causation and selection bias.

Results

In those with primary/no (n = 1312, incidence rate ratio [IRR] = 0.83, 95%CI = 0.70‐0.99) and secondary education (n = 2208, IRR = 0.88, 95%CI = 0.80‐0.97), but not tertiary education (n = 1786, IRR = 0.93, CI = 0.86‐1.00), participating in LLE was associated with lower rate of MoCA errors. The prospective association between LLE and 4‐year change in MoCA‐errors was (borderline) statistically significant in those with primary/no education only (IRR = 0.86, CI = 0.74‐1.00). Sensitivity analyses supported robustness of the findings.

Conclusions

LLE may contribute to cognitive reserve and be a useful intervention to mitigate the increased risk of cognitive decline associated with low levels of education.
Changes in the Global Burden of Chronic Liver Diseases From 2012 to 2017: The Growing Impact of NAFLD
Authors: Paik James M. , Golabi Pegah , Younossi Youssef , Mishra Alita , Younossi Zobair M.
Published: February 2020

Background and Aims

Chronic hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and alcohol‐associated liver disease (ALD) are main causes of chronic liver disease. We assessed the global incidence, mortality, and disability‐adjusted life‐years (DALYs) related to chronic liver disease (primary liver cancer [LC] and cirrhosis).

Approach and Results

We obtained data from the 2017 Global Burden of Disease study. In 2017, there were 2.14 million liver‐related deaths (2.06‐2.30 million), representing an 11.4% increase since 2012 (16.0% increase in LC deaths; 8.7% increase in cirrhosis deaths). LC and cirrhosis accounted for 38.3% and 61.7%, respectively, of liver deaths (LC and cirrhosis deaths were related to HBV [39% and 29%], HCV [29% and 26%], ALD [16% and 25%], and NAFLD [8% and 9%]). Between 2012 and 2017, age‐standardized incidence rate, age‐standardized death rate (ASDR), and age‐standardized DALY rate increased for LC from 11.1 to 11.8, 10.1 to 10.2, and 250.4 to 253.6 per 100,000, respectively. Although age‐standardized incidence rate for cirrhosis increased from 66.0 to 66.3, ASDR and age‐standardized DALY rate decreased from 17.1 to 16.5 and 532.9 to 510.7, respectively. The largest increase in ASDR for LC occurred in Eastern Europe (annual percent change [APC] = 2.18% [0.89%‐3.49%]), whereas the largest decrease occurred in high‐income Asia Pacific (APC = −2.88% [−3.58 to −2.18%]). ASDR for LC‐NAFLD and ALD increased annually by 1.42% (1.00%‐1.83%) and 0.53% (0.08‐0.89), respectively, whereas there were no increases for HBV (P = 0.224) and HCV (P = 0.054). ASDR for cirrhosis‐NAFLD increased (APC = 0.29% [0.01%‐0.59%]) but decreased for ALD (APC = −0.44% [−0.78% to −0.40%]), HCV (APC = −0.50% [−0.81% to −0.18%]), and HBV (APC = −1.43% [−1.71% to −0.40%]).

Conclusions

From 2012 to 2017, the global burden of LC and cirrhosis has increased. Viral hepatitis remains the most common cause of liver deaths, and NAFLD is the most rapidly growing contributor to liver mortality and morbidity.
NINA/LILA debtors under the Portuguese Insolvency Act: A hidden problem in plain sight?
Authors: Frade Catarina , de Jesus Rúben
Published: February 2020

No income, no assets (NINA) and low income, low assets (LILA) debtors are a non‐negligible part of the increasingly ‘financialized’ market economy. Falling outside the financial market or accessing it through low quality financial products, NINA/LILA debtors appear to be under prioritized by both legal and judicial regimes and public policies. Focusing on the legal and judicial dimension, and taking as an illustration the Portuguese context, we discuss how preinsolvency and insolvency solutions still remain ill‐adjusted for such cases. In spite the existence of some legal provisions aiming at fostering access to law and courts regardless individuals' financial conditions, they do not perform very well with insolvent debtors lacking a regular income. Addicionally, there are non‐legal barriers that prevent those with less economic means to fight properly for their social and economic rights.
β‐Selective C−H Arylation of Electron‐Deficient Thiophenes, Pyrroles, and Furans
Authors: Liu Luo‐Yan , Qiao Jennifer X. , Ewing William R. , Yeung Kap‐Sun , Yu Jin‐Quan
Published: February 2020

A general β‐C−H arylation of electron‐deficient thiophenes, pyrroles, and furans has been developed using ligand‐modulated palladium catalyst. The use of a modified norbornene is crucial for reversing the conventional α‐selectivity of these substrates. This method features good yields, high β‐selectivity, and good tolerance of functional groups.
Repression of Kisspeptin1 weakens hydrogen peroxide‐caused injury in HTR8 cells via adjusting PI3K/AKT/mTOR pathway
Authors: Han Qingfang , Zhang Wenke , Lu Caixia , Wu Jixia , An Shujing , Zhang Shiqian
Published: February 2020

Kisspeptin1 (KISS1) is a tumor metastatic suppressor, and its increased expression is validated in human placenta trophoblast cells. Nonetheless, the actions of KISS1 in hydrogen peroxide (H2O2)‐impaired human trophoblast HTR8 cells still remain imprecise. This research aims to uncover whether KISS1 can mitigate H2O2‐triggered cell injury. HTR8 cells were pretreated with 250 μM H2O2 for 4 hours; the autophagic markers (Beclin‐1 and LC3B), cell viability, invasion and apoptosis were appraised. Real‐time quantitative polymerase chain reaction and Western blot trials were enforced for the valuation of KISS1 mRNA and protein levels. After si‐KISS1 transfection and 3‐MA manipulation, the aforesaid biological processes were reassessed for ascertaining the influences of repressed KISS1 in H2O2‐impaired HTR8 cells. Phosphoinositide 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was eventually estimated. H2O2 enhanced Beclin‐1 and LC3B expression, restricted cell viability, and invasion, and meanwhile caused apoptosis. The elevation of KISS1 evoked by H2O2 was observed in HTR8 cells. In addition, silencing KISS1 was distinctly annulled the function of H2O2 in HTR8 cells. Eventually, we observed that the repression of KISS1 triggered the activation of PI3K/AKT/mTOR in HTR8 cells under H2O2 management. The diverting research unveiled that KISS1 repression eased H2O2‐caused HTR8 cells injury via mediating PI3K/AKT/mTOR pathway.
Fractional occupation numbers and self‐interaction correction‐scaling methods with the Fermi‐Löwdin orbital self‐interaction correction approach
Authors: Aquino Fredy W. , Shinde Ravindra , Wong Bryan M.
Published: February 2020

We present a new assessment of the Fermi‐Löwdin orbital self‐interaction correction (FLO‐SIC) approach with an emphasis on its performance for predicting energies as a function of fractional occupation numbers (FONs) for various multielectron systems. Our approach is implemented in the massively parallelized NWChem quantum chemistry software package and has been benchmarked on the prediction of total energies, atomization energies, and ionization potentials of small molecules and relatively large aromatic systems. Within our study, we also derive an alternate expression for the FLO‐SIC energy gradient expressed in terms of gradients of the Fermi‐orbital eigenvalues and revisit how the FLO‐SIC methodology can be seen as a constrained unitary transformation of the canonical Kohn–Sham orbitals. Finally, we conclude with calculations of energies as a function of FONs using various SIC‐scaling methods to test the limits of the FLO‐SIC formalism on a variety of multielectron systems. We find that these relatively simple scaling methods do improve the prediction of total energies of atomic systems as well as enhance the accuracy of energies as a function of FONs for other multielectron chemical species.
Amplified oxadiazole derivative nano MgO–multiwall carbon nanotubes modified carbon paste electrode for the determination of dopamine in presence of morphine
Authors: Vafaee‐Shahi Shohre , Shishehbore M. Reza , Sheibani Ali , Tabatabaee Masoumeh
Published: February 2020

In this paper, we report the fabrication of an amplified sensor to determine dopamine in the presence of morphine based on nano‐MgO, multiwall carbon nanotubes, and an oxadiazole derivative. The electrochemical behavior and electrocatalyic activity of the sensor toward the oxidation of dopamine were investigated. Cyclic voltammetry was used to study the redox features of the sensor, and the results have shown that dopamine overpotential oxidation at the surface of the sensor was reduced to nearly 460 mV. The diffusion coefficient was estimated by chronoamperometry. Three segmented linear dynamic ranges over the range 0.05–5175.0 and detection limit of 0.021 μM for the quantification of dopamine were obtained using differential pulse voltammetry (DPV). The modified nanocomposite carbon paste electrode, which showed excellent sensitivity, selectivity, repeatability, and reproducibility, was satisfactorily employed to determine dopamine and morphine in actual samples.
Diagnostic performance of reticulocyte hemoglobin equivalent in assessing the iron status
Authors: Chinudomwong Pawadee , Binyasing Aleeyas , Trongsakul Rangsiri , Paisooksantivatana Karan
Published: February 2020

Background

Measurement of reticulocyte hemoglobin equivalent (RET‐He) is rapid, convenient, and cost‐effective. Yet, researches on its performance in diagnosing iron deficiency with concurrent inflammation are limited. Hence, this study investigated RET‐He value in various states, including inflammation, and evaluated its diagnostic performance in iron status assessment.

Methods

Retrospectively, 953 clinical data and laboratory results—complete blood count, reticulocyte count, RET‐He, and serum ferritin—were reviewed. Patients on iron therapy were excluded. Iron status was defined by serum ferritin as the reference method. RET‐He among populations was investigated. Its diagnostic performance and optimal cutoff were determined by ROC analysis.

Results

Three population groups were classified: healthy control, iron deficiency anemia (IDA), and non‐ID anemia. Significantly, RET‐He value in IDA was lower than that of healthy control, anemia of inflammation, and chronic kidney disease (P < .0001). Low RET‐He was also observed in IDA with concomitant inflammation despite normal‐to‐high serum ferritin levels. No significant difference was observed between RET‐He values in pure IDA and thalassemia (P = .57). ROC curve analysis revealed AUC of 0.876 (P < .0001) at cutoff 30 pg, by which IDA was discriminated with 74.2% sensitivity and 97.4% specificity. Applying cutoff ≤30 pg, IDA can be diagnosed with 96% sensitivity, 97.4% specificity, 80% PPV, and 99.6% NPV. Hence, RET‐He >30 pg signifies a non‐IDA state.

Conclusion

In addition to convenience and cost‐effectiveness, RET‐He cutoff >30 pg can be potentially used to exclude IDA due to its excellent diagnostic sensitivity and specificity.
Preparation, characterization and antioxidant activity of microspheres made of cellulose triacetate (CTA) to control the release of vitamin C
Authors: Khaldia Sediri , Lamia Bennabi , Yasmina Khane , Lahcene Belarbi
Published: February 2020

BACKGROUND

Biodegradable polymers of natural origin have shown great interest in release of active substances such as antioxidants as a quercetin or ascorbic acid (AA) given its interest in human health, the aim of this study is to make sure of the dissolution of this active ingredient in two reconstituted pH 1.2 (stomach) and pH 7.4, for this it is very important to choose the right matrix and the right method to prepare the good formulations, cellulose acetate is a very important polymer given its easy of obtaining by simple extraction of cotton with good yield using acetic acid and acetic anhydride.

RESULTS

In this work, we encapsulate AA with a mixture of polymers of cellulose triacetate (CTA) and ethylcellulose (EC) as a semi‐crystalline structure by solvent evaporation method. The shape and size of the resulting microspheres were carried out by optical microscopy (OM) and scanning electron microscopy (SEM). The interactions between the active ingredient and the polymers have been studied by Fourier‐transform infrared (FTIR), X‐ray diffraction (XRD), proton nuclear magnetic resonance (1H‐NMR) and carbon‐13 (13C)‐NMR. The results have been shown that the CTA gives a good rapid release of AA at levels relatively higher than 20% which is better in pH 7.4, this is due to the amorphous structure of the matrix used revealed by XRD. When changing the composition of the formulation (EC–CTA), the release rate of the AA is increased and has considerably modified the polydispersity and the shape of the microspheres prepared.

CONCLUSION

We found that the release of AA is more easily achieved in pH 7.4 medium than in the acid medium and this may suggest that this medium promotes the release of AA. The study of antioxidant activity can conclude that the encapsulation by solvent evaporation is a method which preserves the antioxidant character of the active agent using CTA as a matrix. © 2020 Society of Chemical Industry
Thyroid carcinoma metastasizing to the submandibular gland: Sonographic findings
Authors: Golant Brandon T. , Velez‐Perez Anneliese , Krishnamurthy Savitri , Guo Ming , Mousavi Shima , Hu Mimi I. , Varghese Jeena M. , Zafereo Mark E. , Debnam James M.
Published: February 2020

Metastases to the submandibular gland are extremely rare; a literature search retuned only three previously reported cases from a thyroid gland primary site. Herein, we report two cases of metastatic thyroid carcinoma to the submandibular gland in a 64‐year‐old woman with PTC and a 70‐year‐old‐woman with medullary thyroid carcinoma (MTC). The metastases were identified on CT and PET/CT in one case and on CT in the other case, but both were diagnosed with ultrasound‐guided fine‐needle aspiration. Our cases highlight that while rare, both PTC and MTC can metastasize to the submandibular gland.
OPN is a promising serological biomarker for hepatocellular carcinoma diagnosis
Authors: Zhu Mingyu , Zheng Jie , Wu Fei , Kang Bin , Liang Ji , Heskia Fabienne , Zhang Xinxin , Shan Yunfeng
Published: February 2020

Hepatocellular carcinoma (HCC) accounts for 90% of cases of liver cancer and is one of the most common and lethal malignancies among all cancers. Current screening practices in high‐risk populations using ultrasound and serological α‐fetoprotein (AFP) have significantly reduced HCC mortality. However, considering the highly operative‐dependent nature of ultrasound and dissatisfactory diagnostic performance of AFP, there is an unfulfilled need for a biomarker that can be used in HCC‐related at‐risk population screening. Here, sera from 322 patients, including 105 cases of chronic hepatitis (CH), 116 of liver cirrhosis (LC), and 101 of HCC, were collected. Two biomarkers, osteopontin (OPN) and dickkopf WNT signaling pathway inhibitor 1 (DKK1), were evaluated and compared with AFP alone and in combination. In our data, the serum OPN level increased significantly in HCC even in tumors of less than 2 cm. The area under the curve (AUC) reached 0.851, much higher than AFP and DKK1, with 79.21% sensitivity and 79.64% specificity at optimal cutoff in all of the samples. In AFP‐negative samples, serum OPN also performed well with an AUC of 0.838. The combination of AFP and OPN improved diagnosis performance significantly when compared with AFP alone. However, the DKK1 level showed an increase in HCC only compared with the LC group. The AUC does not improve significantly when added into the binary logistic model. We conclude that OPN, but not DKK1, is a promising biomarker for HCC diagnosis.
Vacuolar targeting of aldehyde dehydrogenase 6 tagging with signal peptide of proteinase A
Authors: Park Dong J. , Choi Wooil , Bang Seung H. , Kim Sang Y. , Wee Ji‐Hyang , Kim Yang‐Hoon , Min Jiho
Published: February 2020

Vacuoles are useful materials with antimicrobial and anticancerous properties. Vacuolar proteins can discompose macromolecules from the outside of yeast cells. The objective of this study was to determine the function of a protein transported into a vacuole. Specifically, cytosolic protein aldehyde dehydrogenase 6 (ALD6) was used for the delivery to the vacuole. To transport cytosolic protein to the vacuole in this study, a transfer vector including a signal peptide sequence isolated from vacuolar protein proteinase A was designed. A signal peptide is an amino acid sequence in front of the transported protein. Signal peptides have various delivery pathways according to the kind of signal sequence they contain. They play important roles in transporting proteins to organelles, in cellular mechanisms, and the transfer of protein outside and inside eukaryotes. Thus, we focused on the design of a transfer vector containing a signal peptide sequence isolated from the DNA sequence of proteinase A (PEP4). In addition, this study evaluated the expression level of cytosolic ALD6 after being transported into the yeast vacuole. Our results showed that the developed transfer vector was useful for delivering proteins to vacuole by using signal peptide sequence. Therefore, this transfer vector might be used as a tool to deliver target proteins to organelles of interest in eukaryotes.
A Quantitative Multi‐Criteria Solvent Selection Method for Extraction Processes: Case Study—Downstream Purification of Sucrose‐Based Surfactants
Authors: Chavarrio Javier E. , Gutiérrez María F. , Orjuela Álvaro
Published: February 2020

This work developed a novel method for the identification and selection of green solvents for extraction processes. The methodology was experimentally validated in the downstream separation of sucrose‐based surfactants obtained from a solvent‐free transesterification of sucrose and methyl palmitate (MP). First, a preliminary solvent screening was carried out taking into account environmental consciousness, extraction effectiveness, and predicted operating costs, combining both theoretical and empirical inputs. Potential solvents were first selected from a green solvents list used at the pharmaceutical industry, and the affinity with reactants was assessed based on the Hansen solubility parameters. Solvent suitability was ranked according to a novel objective function that incorporated the heat of vaporization, normal boiling point, cost, and availability. In the case of study, ethyl acetate was identified as the most promising solvent for MP extraction. This and other solvents were experimentally evaluated to validate the selection method and to assess their extraction performance. According to different effectiveness criteria, ethyl acetate was confirmed as the preferable extraction solvent. Finally, MP extraction from reaction media was optimized, varying temperature, number of stages, and solvent loading. Purified sucrose esters were subjected to bleaching obtaining a product under market specifications.
Hair Transplantation in Frontal Fibrosing Alopecia and Lichen Planopilaris: A Systematic Review
Authors: Lee Joshua A. , Levy Dylan A. , Patel Krishna G. , Brennan Emily , Oyer Samuel L.
Published: February 2020

Objective: Evolving hair transplantation (HT) techniques have offered new possibilities for hair restoration. However, the role of HT in patients with frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) remains unclear. This study aims to evaluate the outcomes and temporal relationship of HT in this population.

Methods: A literature search of three databases was conducted. We reviewed 1) literature reporting outcomes of patients with LPP or FFA who received HT, and 2) studies reporting the development of LPP or FFA resulting from HT.

Results: Thirteen articles included 42 patients that provided data for evaluation. Fifteen patients had previously been diagnosed with FFA or LPP, and the remaining 27 patients developed disease after undergoing HT. Seven patients with FFA and eight patients with LPP received HT, with a mean sustained disease remission of 2.69 years prior to HT. In total, two of seven (29%) patients with FFA and five of eight (75%) patients with LPP experienced positive HT results over a follow‐up period of 8–72 months. Interestingly, 27 patients without evidence of previous disease developed FFA or LPP following HT after a median duration of 16 months.

Conclusions: HT for LPP and FFA is feasible but results may be less favorable compared to HT for other causes. Outcomes may be more favorable for LPP than FFA but this was not statistically significant and evidence is very limited. FFA and LPP can also develop following HT in patients without previous evidence of disease.

Level of Evidence: NA Laryngoscope, 131:59–66, 2021