bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal Tolerability and Absorption ofR‐VersusR,S‐Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial
Authors: Cameron Michelle , Taylor Cassidy , Lapidus Jodi , Ramsey Katrina , Koop Dennis , Spain Rebecca
Published: March 2020

We compared the gastrointestinal (GI) tolerability and assessed for bioequivalent absorption ofR‐lipoic acid (LA) in people with progressive multiple sclerosis (MS) in a single‐center, double‐blind, randomized crossover trial. Participants randomly assigned to formulation sequence took 600 mg ofR‐LA or 1200 mg of a 1:1 racemicR,S‐LA mixture in single daily doses for 7 to 10 days, underwent a washout of at least 7 days, and then took the other form of LA for 7 to 10 days. At the end of each period on LA, GI symptoms were assessed with GI questions from the Monitoring of Side Effects Scale. Serum LA concentrations were measured before and 60, 90, 120, 180, and 240 minutes after the first and last day's dose of each form of LA to derive an area under the plasma concentration–time curve (AUC) and maximum serum concentration (Cmax). Twenty participants enrolled (12 women; 15 secondary progressive MS, 5 primary progressive MS; mean age, 59.6 years). Two withdrew early due to symptoms while takingR,S‐LA, and one withdrew early while takingR‐LA. The mean GI Monitoring of Side Effects Scale score was 1.7 points lower onR‐LA than onR,S‐LA (P= .069), and there were fewer reports of each GI side effect when taking theR‐LA than theR,S‐LA (31 vs 60;P= .025). The AUC and CmaxforR‐LA were bioequivalent for the 2 formulations (90% confidence intervals 97.4% to 99.3% for AUC and 93.4% to 98.2% for Cmax). This study supports that in people with progressive MS, there is better GI tolerability and bioequivalent serum absorption ofR‐LA when 600 mg ofR‐LA is taken asR‐LA alone than when taken in a 1:1 racemicR,S‐LA mixture.
Addressing the spatial disconnect between national‐scale total maximum daily loads and localized land management decisions
Authors: Amin M. G. Mostofa , Veith Tamie L. , Shortle James S. , Karsten Heather D. , Kleinman Peter J. A.
Published: March 2020

Regulatory watershed mitigation programs typically emphasize widespread adoption of best management practices (BMPs) to meet total maximum daily load (TMDL) goals. To comply with the Chesapeake Bay TMDL, jurisdictions must develop watershed implementation plans (WIPs) to determine the number and type of BMPs to implement. However, the spatial resolution of the bay‐level model used to determine these load reduction goals is so coarse that the regulatory plan cannot consider heterogeneity in local conditions, which affects BMP effectiveness. Using the Topo‐SWAT modification of the Soil and Water Assessment Tool (SWAT), we simulated two BMP adoption scenarios in the Spring Creek watershed in central Pennsylvania to determine if leveraging fine‐scale spatial heterogeneity to place BMPs could achieve the same (or better) nutrient and sediment reduction at a lower cost than the state‐level WIP BMP adoption recommendations. Topo‐SWAT was initialized with detailed land use and management practice information, systematically calibrated, and validated against 12 yr of observed data. After determining individual BMP cost effectiveness, results were ranked to design a cost‐effective BMP adoption scenario that achieved equal or greater load reduction as the WIP scenario for 74% of the cost using eight management‐based BMPs: no‐till, manure injection, cover cropping, riparian buffers, land retirement, manure application timing, wetland restoration, and nitrogen management (15% less N input). Because watersheds of this size typically represent the smallest modeling unit in the Chesapeake Bay Model, results demonstrate the potential to use watershed models with finer inference scales to improve recommendations for BMP implementation under the Chesapeake Bay TMDL.
Environmentally friendly and efficient method for the synthesis of the new α,α′‐diimine ligands with benzimidazole moiety
Authors: Mamedov Vakhid A. , Zhukova Nataliya A. , Kadyrova Milyausha S. , Fazleeva Rezeda R. , Bazanova Olga B. , Beschastnova Tat'yana N. , Gubaidullin Aidar T. , Rizvanov Il'dar Kh. , Yanilkin Vitaliy V. , Latypov Shamil K. , Sinyashin Oleg G.
Published: March 2020

The new α,α′‐diimine ligands with benzimidazole moiety were synthesized based on the rearrangement of 3‐aroylquinoxalin‐2(1H)‐ones when exposed to 4,5‐diamino‐2,1,3‐benzoxadiazole, 4,5‐diamino‐2,1,3‐benzothiadiazole and 5,6‐diaminoquinoxaline. Among them, we report the first examples of the new heterocyclic system namely benzo[4′,5′]imidazo[1′,2′:1,2]quinolino[3,4‐b and 4,3‐b][1,2,5]oxadiazolo[3,4‐f]quinoxalines, which exhibits an interesting electrochemical behavior. All compounds were fully characterized by IR, 1H and 13C NMR spectroscopies, and mass spectrometry.
Synthesis of isotopically labelled αCGRP8‐37 and its lipidated analogue
Authors: Lu Benjamin L. , Loomes Kerry M. , Hay Debbie L. , Harris Paul W.R. , Brimble Margaret A.
Published: March 2020

α‐Calcitonin gene related peptide (αCGRP) inhibitors are important medicinal targets due to their ability to produce antimigraine effects, thus, the discovery of long‐acting αCGRP inhibitors is of significant interest. Herein we report the synthesis of an isotopically labelled version of the well‐known CGRP receptor antagonist, αCGRP8‐37, as well as lipidated αCGRP8‐37 with comparable antagonistic activity. These isotopically labelled peptides can be employed in assays to determine the metabolic stability of the lipidated αCGRP8‐37 and compare this with the stability of known αCGRP8‐37.
Conditioning adhesive contacts between the neutrophils and the endotheliocytes by Staphylococcus aureus
Authors: Pleskova Svetlana N. , Kriukov Ruslan N. , Bobyk Sergey Z. , Boryakov Alexey V. , Gorelkin Peter V. , Erofeev Alexander S.
Published: March 2020

We have developed a model for evaluating the integral intercellular interactions in the “endotheliocyte‐neutrophil” system and have shown the high variability of adhesion contacts in different donors associated with different expression profiles of neutrophils. Two methods (forсe spectroscopy‐spectroscopy and scanning ion‐conductance microscopy) showed a decrease in the rigidity of the membrane‐cytoskeletal complex of neutrophils under the influence of Staphylococcus aureus 2879 M. Adding this strain to the “endotheliocyte‐neutrophil” system caused a statistically significant decrease in the adhesion force and adhesion work, which indicates a change in the expression profile and physicochemical properties of membranes of both types of interacting cells (neutrophils and endotheliocytes).
Potential of proteomics to probe microbes
Authors: Shiny Matilda Chellaiah , Madhusudan Iyengar , Gaurav Isola Ravi , Shanthi Chittibabu
Published: March 2020

An organism exposed to a plethora of environmental perturbations undergoes proteomic changes which enable the characterization of total proteins in it. Much of the proteomic information is obtained from genomic data. Additional information on the proteome such as posttranslational modifications, protein–protein interactions, protein localization, metabolic pathways, and so on are deduced using proteomic tools which genomics and transcriptomics fail to offer. The proteomic analysis allows identification of precise changes in proteins, which in turn solve the complexity of microbial population providing insights into the microbial metabolism, cellular pathways, and behavior of microorganisms in new environments. Furthermore, they provide clues for the exploitation of their special features for biotechnological applications. Numerous techniques for the analysis of microbial proteome such as electrophoretic, chromatographic, mass spectrometric‐based methods as well as quantitative proteomics are available which facilitate protein separation, expression, identification, and quantification of proteins. An understanding of the potential of each of the proteomic tools has created a significant impact on diverse microbiological aspects and the same has been discussed in this review.
Dummy template surface molecularly imprinted polymers based on silica gel for removing imidacloprid and acetamiprid in tea polyphenols
Authors: Chen Jingyu , Huang Xin , Wang Li , Ma Chaoyang , Wu Shijia , Wang Hongxin
Published: March 2020

Dummy template surface molecularly imprinted polymers based on silica gel were prepared through the surface molecular imprinting technique. Nonpoisonous nicotinamide, which is a structural analogue of imidacloprid and acetamidine, was chosen as the dummy template molecule. The obtained polymers were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and X‐ray diffraction. The results showed that the polymers exhibited high adsorption capacity and selectivity for imidacloprid and acetamiprid. The maximum adsorption capacities of the polymers toward imidacloprid and acetamiprid were 42.05 and 22.99 mg/g, and the adsorption could reach binding equilibrium within 150 min. The polymers were successfully applied as column‐filling materials to extract imidacloprid and acetamiprid from tea polyphenols with a relatively high removal rate (92.36 and 95.20%). The polymers also showed great stability and reusability during the application. The obtained polymers possessed good application prospects for removing imidacloprid and acetamiprid in tea polyphenol production processes.
Nucleus Hybrid S12: Multicenter Clinical Trial Results
Authors: Dunn Camille C. , Oleson Jacob , Parkinson Aaron , Hansen Marlan R. , Gantz Bruce J.
Published: March 2020

Objectives/Hypothesis

The use of a short 10‐mm/10‐electrode cochlear implant to preserve low‐frequency residual hearing was investigated. This report describes the 12‐month outcomes of this multicenter clinical trial.

Study Design

Single‐subject design.

Methods

Twenty‐eight subjects with low‐frequency hearing at or better than 60 dB HL at 500 Hz and severe high‐frequency hearing loss were implanted with a Nucleus Hybrid S12 implant in their poorer ear. Speech perception in quiet using Consonant‐Nucleus‐Consonant (CNC) words and sentences in noise using AzBio sentences was collected pre‐ and postoperatively at 3, 6, and 12 months. Subjective reporting using the Speech, Spatial, and Qualities of Hearing Scale (SSQ) questionnaire was also collected pre‐ and postoperatively.

Results

Functional hearing preservation was accomplished in 96% of subjects. At 3 and 6 months, 86% of the 28 subjects had maintained functional hearing. By 12 months, 23 out of 27 subjects (85%) had maintained functional hearing (one subject with functional hearing at 6 months withdrew from the study prior to the 12‐month visit). Speech perception results demonstrated that 81% of the participants on CNC words and 77% with AzBio sentences in noise had significant improvements using their everyday listening condition at 12 months compared to preoperative performance with bilateral hearing aids. Furthermore, preoperative to 12 months postoperative subjective ratings showed significant improvements for the SSQ.

Conclusions

This study demonstrates that a high degree of hearing preservation enabling acoustic‐electric hearing and improvement in speech understanding in quiet and in noise can be accomplished using a short‐electrode 10‐mm cochlear implant.

Level of Evidence

2c Laryngoscope, 130:E548–E558, 2020
Aqueous Palladium‐Catalyzed Direct Arylation Polymerization of 2‐Bromothiophene Derivatives
Authors: Lin Yu‐Jen , Sun Han‐Sheng , Yang Hau‐Ren , Lai Yu‐Ying , Hou Kai‐Yuan , Liu Yi‐Hung
Published: March 2020

Aqueous palladium‐catalyzed direct arylation polymerization (DArP) of 2‐bromothiophene derivatives 6‐(2‐(2‐bromothiophen‐3‐yl)ethoxy)hexyl trimethylammonium bromide (T1) and 4‐(2‐(2‐bromothien‐3‐yl)ethoxy)butylsulfonate (T2) is achieved. The supporting ligand, triphenylphosphine‐3,3′,3′′‐trisulfonic acid trisodium salt (m‐TPPTs), facilitates DArP of both derivatives; however, its separation from the polymers by dialysis is difficult due to its strong aggregation in water and N,N‐dimethylacetamide (DMAc). This is supported by dynamic light scattering, gel permeation chromatography (GPC), and single‐crystal X‐ray crystallography. Pyrimidine–Pd(OAc)2 is utilized in the DArP of T1 to afford PT1 without ligand contamination. Density functional theory calculations to determine the coordinating capability of the carboxylate/pivalic acid/water to palladium indicate the viability of implementing DArP in water. Finally, polyelectrolyte molecular‐weight overestimation by GPC in water is attributed to the polyelectrolyte effect. Aggregation of the conjugated polyelectrolytes leads to a contracted hydrodynamic volume, and the molecular weight and dispersity assessed by GPC in DMAc significantly deviate from the actual values. An objective approach to evaluate the molecular weight for conjugated polyelectrolytes requires further development.
Genomic profiling reveals the pivotal role of hrHPV driving copy number and gene expression alterations, including mRNA downregulation of TP53 and RB1 in penile cancer
Authors: Macedo Juliana , Silva Elis , Nogueira Leudivan , Coelho Ronald , da Silva Jenilson , dos Santos Alcione , Teixeira‐Júnior Antônio Augusto , Belfort Marta , Silva Gyl , Khayat André , de Oliveira Edivaldo , dos Santos Ana Paula , Cavalli Luciane R. , Pereira Silma Regina
Published: March 2020

The incidence of penile cancer (PeCa) is increasing worldwide, however, the highest rates are reported in underdeveloped countries. The molecular mechanisms that underly the onset and progression of these tumors are still unclear. Therefore, our goal was to determine the genome‐wide copy number alterations and the involvement of human papiloma virus (HPV) (TP53 and RB1), inflammatory (COX2 and EGFR), and PI3K/AKT pathway (AKT1, AKT2, EGFR, ERBB3, ERBB4, PIK3CA, and PTEN) associated genes in patients with PeCa from a high incidence region in Brazil (Maranhão). HPV genotyping was performed by nest‐PCR and genome sequencing, copy number alterations (CNAs) by array comparative genomic hybridization and gene copy number status, gene, and protein expression by quantitative polymerase chain reaction, reverse transcriptase‐quantitative polymerase chain reaction, and immunohistochemistry, respectively. HPV genotyping revealed one of the highest frequencies of HPV reported in PeCa, affecting 96.4% of the cases. The most common CNAs observed were located at the HPV integration sites, such as 2p12‐p11.2 and 14q32.33, where ADAM 6, KIAA0125, LINC00226, LINC00221, and miR7641‐2, are mapped. Increased copy number of ERBB3 and EGFR genes were observed in association with COX2 and EGFR overexpression, reinforcing the role of the inflammatory pathway in PeCa, and suggesting anti‐EGFR and anti‐COX2 inhibitors as promising therapies for PeCa. Additionally, TP53 and RB1 messenger RNA downregulation was observed, suggesting the occurrence of other mechanisms for repression of these oncoproteins, in addition to the canonical HPV/TP53/RB1 signaling pathway. Our data reinforce the role of epigenetic events in abnormal gene expression in HPV‐associated carcinomas and suggest the pivotal role of HPV driving CNAs and controlling gene expression in PeCa.
Parkinsonism Versus Concomitant Parkinson's Disease in Fragile X–Associated Tremor/Ataxia Syndrome
Authors: Salcedo‐Arellano María Jimena , Wolf‐Ochoa Marisol Wendy , Hong Tiffany , Amina Sarwat , Tassone Flora , Lechpammer Mirna , Hagerman Randi , Martínez‐Cerdeño Verónica
Published: March 2020

Background

Fragile X–associated tremor/ataxia syndrome (FXTAS) is a late‐onset neurodegenerative disorder associated with premutation alleles (55–200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. FXTAS is characterized by the presence of ubiquitin‐positive inclusions in neurons and astrocytes and by cerebellar tremor and ataxia. Parkinsonism has been reported in FXTAS, but most patients lack the characteristic rest tremor and severe rigidity seen in idiopathic Parkinson's disease (PD).

Objective

To describe the frequency of concomitant PD in FXTAS.

Methods

We reviewed the medical record of 40 deceased patients diagnosed with FXTAS and performed a pathology analysis to confirm both FXTAS and PD.

Results

Clinical histories indicated that 5 FXTAS patients were diagnosed with idiopathic PD and 2 with atypical parkinsonian syndrome. After pathological examination, we found that 7 patients in the PD clinical diagnosis group had dopaminergic neuronal loss; however, only 2 of 7 presented Lewy bodies (LBs) in the substantia nigra. Therefore, a total of 5% of the 40 cohort patients met the pathologic criteria for the concomitant diagnosis of FXTAS and PD. In addition, 2 patients not clinically diagnosed with PD also had nigral neuronal loss with LBs in substantia nigra. In total 10% of these 40 patients had LBs.

Conclusion

This report expands our understanding of clinical symptoms and unusual presentations in patients with FXTAS and the concept that the parkinsonism found in FXTAS is sometimes indistinguishable from PD. We propose that FMR1 should be recognized as one of the exceptional genetic causes of parkinsonism with presynaptic dopaminergic loss and LBs.
Prevalence of ABCC3‐1767G/A polymorphism among patients with antiretroviral‐associated hepatotoxicity
Authors: Singh HariOm , Lata Sonam , Choudhari Ranjana , Dhole Tapan N.
Published: March 2020

Background

Plasma concentrations of antiretrovirals (ARVs) regimens have considerably varied in individuals of human immunodeficiency virus (HIV) because of variations in the expression of drug‐metabolizing and transporter genes. Transporter genes play an important role in the disposition of drugs. Polymorphism in transporter gene (ABCC3) affects the MRP3 expression and varies the treatment outcome.

Method

We examined the polymorphism of ABCC3‐1767G/A gene in a total of 165 HIV patients (out of 165 HIV patients, 34 were with and 131 were without hepatotoxicity) and 156 healthy individuals using the polymerase chain reaction–restriction fragment length polymorphism method.

Results

In univariate analysis, we found a decreased prevalence of ABCC3 1767GA, 1767GA+AA genotypes, and 1767A allele in patients with hepatotoxicity as compared to patients without hepatotoxicity (23.5% vs. 28.2% and 23.5% vs. 30.53%; 11.76% vs. 16.41%), while a higher prevalence of 1767AA genotype was observed in HIV patients in comparison with healthy controls (2.3% vs. 1.3%, odds ratio [OR] = 1.71, 95% confidence interval [CI]: 0.23–15.03, p = .89). The frequency of ABCC3‐1767AA genotype was dispersed higher in individuals with early and advanced HIV disease stage in comparison with healthy controls (5.3% vs. 1.3%, OR = 4.73, p = .70; 8.9% vs. 1.3%, OR = 1.89, p = .91). A higher occurrence of ABCC3‐1767AA genotype was found in tobacco using HIV patients without hepatotoxicity compared with nonusers (4.7% vs. 1.1%, OR = 4.28, p = .52). The distribution of ABCC3‐1767GA genotype was higher in nevirapine receiving HIV patients irrespective of their hepatotoxicity status as compared to nonusers (30.4% vs. 9.1%, OR = 3.34, p = .22; 29.4% vs. 16.7%, OR = 1.69, p = .77). In multivariate analysis, HIV patients receiving nevirapine and with hepatotoxicity was found to have a significant risk for severity of hepatotoxicity (OR = 4.56, 95% CI: 1.60–12.99, p = .004).

Conclusion

ABCC3 1767G/A polymorphism was not significantly associated with susceptibility to ARV‐associated hepatotoxicity, although ABCC3 1767AA genotype designated a risk for acquisition of hepatotoxicity and advancement of the disease. Nevirapine usage emerged as an independent risk factor for hepatotoxicity severity.
Rayleigh–Taylor instability for nonhomogeneous incompressible fluids with Navier‐slip boundary conditions
Authors: Ding Shijin , Ji Zhijun , Li Quanrong
Published: March 2020

This paper is concerned with the Rayleigh–Taylor instability for the nonhomogeneous incompressible Navier–Stokes equations with Navier‐slip boundary conditions around a steady state in an infinite slab, where the Navier‐slip coefficients do not have defined sign and the slab is horizontally periodic. Motivated by Jiang et al. (Sci. China Math., 2013), we extend the result from Dirichlet boundary condition to Navier‐slip boundary conditions. Our results indicate the factor that “heavier density with increasing height” still plays a key role in the instability under Navier‐slip boundary conditions.
Sleep disorders in myotonic dystrophies
Authors: Subramony Sub H. , Wymer James P. , Pinto Belinda S. , Wang Eric T.
Published: March 2020

Myotonic dystrophies (DM), the most common muscular dystrophies, are known to have significant sleep disturbances. We analyzed the literature on sleep and excessive daytime sleepiness (EDS) in DM over the past 30 years. In this review we provide a brief overview of sleep, sleep disorders, and methods of assessment. We also analyze data regarding major sleep disorders in DM patients, including: sleep‐disordered breathing (SDB), with both central and obstructive sleep apneas (CSA,OSA); EDS; sleep‐related movement disorders; and poor sleep quality. We review the possible pathogenesis of these disorders and outline management strategies. We also consider possible future avenues for research. The findings highlight the complex set of sleep‐related problems, including the primary abnormality of sleep control in myotonic dystrophies. In individual patients the roles of poor sleep hygiene, SDB, primary hypersomnia, and excess fatigue require careful assessment for appropriate management.
A hybrid material‐point spheropolygon‐element method for solid and granular material interaction
Authors: Jiang Yupeng , Li Minchen , Jiang Chenfanfu , Alonso‐Marroquin Fernando
Published: March 2020

Capturing the interaction between objects that have an extreme difference in Young's modulus or geometrical scale is a highly challenging topic for numerical simulation. One of the fundamental questions is how to build an accurate multiscale method with optimal computational efficiency. In this work, we develop a material‐point‐spheropolygon discrete element method (MPM‐SDEM). Our approach fully couples the material point method (MPM) and the spheropolygon discrete element method (SDEM) through the exchange of contact force information. It combines the advantage of MPM for accurately simulating elastoplastic continuum materials and the high efficiency of DEM for calculating the Newtonian dynamics of discrete near‐rigid objects. The MPM‐SDEM framework is demonstrated with an explicit time integration scheme. Its accuracy and efficiency are further analyzed against the analytical and experimental data. Results demonstrate this method could accurately capture the contact force and momentum exchange between materials while maintaining favorable computational stability and efficiency. Our framework exhibits great potential in the analysis of multi‐scale, multi‐physics phenomena.
Rapid free‐vibration analysis with model reduction based on coherent nodal clusters
Authors: Krysl Petr , Sivapuram Raghavendra , Abawi Ahmad T.
Published: March 2020

Modal expansion is a workhorse used in many engineering analysis algorithms. One example is the coupled boundary element‐finite element computation of the backscattering target strength of underwater elastic objects. To obtain the modal basis, a free‐vibration (generalized eigenvalue) problem needs to be solved, which tends to be expensive when there are many basis vectors to compute. In the above‐mentioned backscattering example it could be many hundreds or thousands. Excellent algorithms exist to solve the free‐vibration problem, and most use some form of the Rayleigh‐Ritz (RR) procedure. The key to an efficient RR application is a low‐cost transformation into a reduced basis. In this work, a novel, inexpensive a priori transformation is constructed for solid‐mechanics finite element models based on the notion of coherent nodal clusters. The inexpensive RR procedure then leads to significant speedups of the computation of an approximate solution to the free vibration problem.
The impact of clean energy consumption on economic growth and CO2 emissions in BRICS countries: Does the environmental Kuznets curve exist?
Authors: Ummalla Mallesh , Goyari Phanindra
Published: March 2020

This paper examines the impact of clean energy consumption (CEC) on economic growth (EG) and CO2 emissions (CO2) within a framework of environmental Kuznets curve (EKC) hypothesis in a panel of BRICS countries for the period 1992–2014. The results indicated that CEC and EG have a significant positive impact on EG, while CO2 has a negative impact on it. Our results also found that EC and EG increase CO2 while CEC significantly reduces it. Further, we found that the EKC hypothesis is valid in the BRICS countries. Finally, panel causality test indicated that unidirectional causality running from EC to EG. However, we did not find a causal relationship between CEC and EG. Based on these results, some of the policy implications have proposed for these emerging market economies.
What types of real‐world evidence studies do U.S. commercial health plans cite in their specialty drug coverage decisions?
Authors: Panzer Ari D. , Margaretos Nikoletta M. , Lai Rachel C. , Enright Daniel E. , Chambers James D.
Published: March 2020

Purpose

To examine the RWE U.S. commercial health plans cite in their specialty drug coverage decisions.

Methods

We used the Tufts Medical Center Specialty Drug Evidence and Coverage Database to identify specialty drug coverage decisions (n = 7267) issued by 17 large commercial health plans. We categorized the clinical evidence plans cited in these coverage decisions (n = 5227) as randomized controlled trials (RCTs), RWE studies, and other clinical studies (studies other than RCT or RWE study). We categorized RWE studies with respect to study type, for example, case series, studies based on medical records, and so on. We compared the frequency that plans cited different categories of RWE, cited RWE for different diseases, and cited RWE for drugs on the market for different time periods.

Results

RWE comprised 16% of cited clinical studies. Health plans cited RWE with different frequencies (5%‐31% of the cited clinical evidence). Overall, plans cited RWE categorized as medical records most often (26% of cited RWE studies). Plans varied in the frequency they cited different RWE categories. Plans most frequently cited RWE for gastroenterological diseases (35% of clinical study citations) and least frequently for respiratory diseases (11% of clinical study citations). Plans cited RWE more for drugs that have long been on the market.

Conclusions

Health plans varied with respect to the number and types of RWE studies they cited in their specialty drug coverage decisions. Plans cited RWE more often for some diseases than others, and cited more RWE for older drugs.
Readmission drivers for children with medical complexity: Home nursing shortages cause health crises
Authors: Sobotka Sarah A. , Lynch Emma , Peek Monica E. , Graham Robert J.
Published: March 2020

Objective

Children with medical technology dependence (MTD) are frequently readmitted to the hospital. However, due to their medical fragility, it is often difficult to untangle the root causes for readmissions to identify the most effective preventive approaches. We sought to explore environmental and family factors driving hospital readmissions for children with MTD.

Design

Semi‐structured, in‐person interviews were conducted with state‐wide care coordinators for children with MTD in Illinois with at least 1 year of experience. Interview topics related to children with MTD transitioning from hospital‐to‐home, essential supports for living in the community, and factors which influenced and prevented hospital readmission. The interview guide served as an initial codebook which was iteratively modified as themes emerged.

Results

Fifteen care coordinators with on average 6.6 years of experience were interviewed. They described that lack of home nursing was one of the primary drivers of readmissions due to parental exhaustion and lack of medical expertize in the home. Unavoidable medical admissions, a lack of a plan for emergencies, and home environmental factors also contributed to readmissions.

Conclusion

Hospital readmission is an expected occurrence for children with MTD, yet still may be substantially reduced through consistent, quality home health nursing to bolster family capacity and allow for respite from constant caregiving. Improved incentives for the home health workforce to increase manpower would be ultimately offset by reduced hospitalizations for children with MTD. Additionally, more research is needed to understand which home nursing structures and skills optimally support families in the reality of manpower scarcity.
Ion Gel‐Gated Nonvolatile Formation of Lateral MoTe2 Diode for Self‐Powered Near‐Infrared Photodetection
Authors: Zhang Qingfu , Zhuge Fuwei , Xie Fengjun , Yu Jun , Yu Shiwen , Zhai Tianyou
Published: March 2020

Electrostatic gates by ion liquid (IL) or ion gel (IG) have allowed the exploration of intriguing material properties that are related to heavy charge doping in low‐dimensional materials. However, the obtained gate modulation is usually volatile at room temperature due to the recovery of ion position when removing the gate bias, which hinders their application in practical functional devices. Herein, the electrochemical IG gate is explored, and a nonvolatile modulation of the doping polarity of MoTe2 (from n to p and reversibly to n) by exploiting the electrochemical hydrolysis of residual water in IG and the subsequent chemical ion adsorption on MoTe2 is demonstrated. Further, based on the asymmetrically coupled gate bias to source and drain terminals, a lateral pn diode is prepared with long‐term stability >5 × 104 s and a self‐powered responsivity >85 mA W−1 at the near‐infrared wavelength of 1050 nm. The performance of diode is further optimized by applying a slight gate bias that tunes the width, position of space charge region in junction, and the overall charge collection efficiency. The nonvolatile electrochemical IG gate thus offers a viable pathway toward 2D low‐power photodetectors in the infrared spectra range.
Convective organization and eastward propagating equatorial disturbances in a simple excitable system
Authors: Vallis Geoffrey K. , Penn James
Published: March 2020

We describe and illustrate a mechanism whereby convective aggregation and eastward propagating equatorial disturbances, which are similar in some respects to the Madden–Julian Oscillation (MJO), arise. We construct a simple explicit system consisting only of the shallow‐water equations plus a humidity variable; moisture enters via evaporation from a wet surface, is transported by the flow and removed by condensation, thus producing an anomaly in the height field. For a broad range of parameters the system is excitable even when linearly stable, with condensation producing convergence and gravity waves that, acting together, trigger more condensation. On the equatorial β‐plane the convection first aggregates near the Equator, generating patterns related to those encountered in the Matsuno–Gill problem. However, the pattern is unstable and more convection is triggered on its eastern edge, leading to a self‐sustaining precipitating disturbance that progresses eastward. The propagation is eastward because the warm, moist converging air from the east induced by the Matsuno–Gill pattern is more convectively unstable than the converging air from the west. The pattern is confined to a region within a few deformation radii of the Equator, as here the convection can create the convergence needed to organize itself into a self‐sustaining pattern; thus, smaller values of the beta parameter give rise to a wider disturbance. Formation of the disturbance preferentially occurs where the surface is warmer, and sufficient time (typically a few tens of days) must pass before conditions arise that enable the disturbance to reform, a well‐known characteristic of the MJO. The speed of the disturbance depends on the efficiency of evaporation and the heat released by condensation, and is typically a few metres per second, much less than the Kelvin wave speed.
Novel Acetylcholinesterase Inhibitors Identified from ZINC Database Using Docking‐Based Virtual Screening for Alzheimer's Disease.
Authors: Ahmed Ali Abdusalam Ashraf , Vikneswaran Murugaiyah
Published: March 2020

Alzheimer's disease (AD) is a neurodegenerative disease related to ageing. Cholinesterases are a family of enzymes that catalyse the hydrolysis of acetylcholine (ACh), which is an essential process in the cholinergic neurotransmission. Cholinesterases can be divided into two types, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). This paper reports virtual screening and molecular docking of 200 compounds obtained from the ZINC database, using AutoDock Vina and AutoDock 4.2 to find potential AChE inhibitors. Only compounds that are compliant with Lipinski's rule of five for drug‐likeness properties were virtually screened to identify novel compounds that show similar or better interaction with the target protein compared to the coordinated ligand galantamine. The results showed that 6 compounds, namely ZINC10140364, ZINC08061148, ZINC34735322, ZINC05151975, ZINC33126088 and ZINC15805418, exhibited better free energy of binding (FEB) than galantamine, with AutoDock Vina scores of −9.88, −10.44, −10.30, −9.63, −8.35 and −9.42 kcal/mol and AutoDock scores of −12.3, −11.6, −11.0, −10.9, −10.5 and −9.3 kcal/mol, respectively. In conclusion, the results obtained suggest that the 6 compounds are potential AChE inhibitors suitable for further evaluation and development as potential agents for treatment.
Interaction of Water at the Hydrophobic Interface of Alkyl Group of Alcohol with p‐Nitro‐Aniline Charge Transfer State
Authors: Parida Smruti Ranjana , Mohapatra Himansu , Priyadarshini Snigdhashree
Published: March 2020

The evolution of photo‐induced intra molecular charge transfer (ICT) transition energy of p‐nitro‐aniline (PNA), with respect to the mole fraction of alcohol in alcohol water mixture has been used to study, the interaction of hydrophobic hydration ‐shell of linear alcohols with PNA‐ICT state. The linear alcohol ranges from methanol to propanol. The plot of absorption energy of PNA charge transfer transition versus mole fraction of alcohol shows the following features. At lower mole fraction of alcohol, the absorption energy of PNA versus mole‐fraction of alcohol plot at first, decreases below the absorption energy of PNA recorded in pure water and alcohol, goes through a minimum and then increases. Similar behaviour is obtained even after subtracting the contribution from dielectric non‐ideality. The behaviour at lower mole fraction thus indicates the modification of specific interaction of PNA with water due to the presence of alcohol. Further, the absorption energy minimum shifts towards lower mole fraction of alcohol as the chain length of alcohol increases. These results, thus reveals the interaction of PNA with the modified water structure at the hydrophobic interface of alkyl group and supports the current understanding of hydrophobic hydration. To our knowledge, this study for the first time reveals that, hydration shell around hydrophobic group has higher ability to stabilize the PNA‐ICT state by hydrogen bonding interaction compared to bulk water.
D‐π‐A Molecular Probe to Unveil the Role of Solute‐Solvent Hydrogen Bonding in Solvatochromism, Location Specific Preferential Solvation and Synergistic Effect in Binary Mixtures
Authors: Kumar Malik Prakash , Tripathy Madhusmita , Patel Sabita
Published: March 2020

An azo dye 4‐(p‐Nitrophenylazo) phenol (NPAP) characterized with a donor‐π‐acceptor (D‐π‐A) framework has been used as a molecular probe to study solvatochromic behavior in neat and binary solvent mixtures comprised of chloroform (a hydrogen bond donor; HBD solvent) and a hydrogen bond acceptor (HBA) solvent. The specificity of the probe lies in its inherent characteristics of having a HBD group and a HBA group at two different ends of the conjugated π‐network. UV‐Vis spectroscopic technique is used for the purpose. The probe demonstrates a very expressive reversal in solvatochromic behavior, with the solvatochromic switch at ET(30) of ∼45 kcal mol−1. Multiparametric treatment of the solvatochromic data using SEV technique displays excellent sensitivity of the probe towards HBA basicity, dipolarity and polarizability of the medium with a smaller but significant contribution from HBD acidity and hydrophobicity/apolarity. The event of preferential solvation in the chloroform‐HBA mixture is explained on the basis of specific solute‐solvent interaction through HBD and HBA ability of the solvent components. HBA solvents preferentially solvate the phenolic site while HBD solvents preferentially solvate the nitrobenzene group through complementary hydrogen bonding, which results in an increase in local concentration at specific sites resulting in synergistic preferential solvation. The proposition of site selective PS through molecular recognition is also supported by theoretical studies.
An Electropolymerized Molecularly Imprinted Electrochemical Sensor for the Selective Determination of Bisphenol A Diglycidyl Ether
Authors: Li Jiayong , Ma Ya , Zeng Qiang , Wang Min , Wang Lishi
Published: March 2020

In this manuscript, a sensitive and selective molecular imprinted electrochemical sensor for the detection of bisphenol A diglycidyl ether (BADGE) in canned oil was developed. Using BADGE as template, pyrrole as functional monomer, after electropolymerization and elution processes, the molecular imprinted film for the special recognition of BADGE was prepared on the surface of platinum disk electrode. Every step in the experiment was verified by field emission scanning electron microscope (SEM), microscopic fourier transform infrared spectroscopy (Micro‐FTIR), cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The experimental parameters in the assay were optimized, and the linear range of the MIP sensor was 0.05 μmol dm−3 to 10 μmol dm−3 with the detection limit of 0.04 μmol dm−3 based on S/N=3. The sensor was applied to edible oil samples for detection with a good accuracy, which could be used as a new strategy for sensitive, rapid, simple and cost‐effective screening of BADGE.
Synthesis of Bis(trimethylsilyl)acetylene (BTMSA) by Direct Reaction of CaC2 with N‐(trimethylsilyl)imidazole
Authors: Liu Shuaishuai , Yin Shuai , Zhang Zhaofu , Liu Huizhen , Liu Mingyang , Han Buxing
Published: March 2020

In this work, we discovered that bis(trimethylsilyl)acetylene (BTMSA) could be synthesized by the reaction of calcium carbide (CaC2) directly with N‐(trimethylsilyl)imidazole (TMSIm) in dichloromethane using CuBr as the catalyst, and reaction could occur efficiently at 100 °C. Control experiment indicated that the reaction did not proceed via acetylene pathway. As far as we know, this is the first work for BTMSA synthesis by direct reaction of CaC2 and a silylation reagent under mild conditions.
Multicomponent Reaction of Pyridinium Salts, β‐Nitrostyrenes and Ammonium Acetate under the DBU/Acetic Acid System: Access to 2,4,6‐Triarylpyridine Derivatives
Authors: Li Mingshuang , Wang Ting , Wang Cunde
Published: March 2020

A four‐component reaction of pyridinium salts, substituted β‐nitrostyrenes and ammonium acetate as a nitrogen source using acetic acid as solvent was investigated to develop an efficient divergent route for the synthesis of 2,4,6‐trisubstituted pyridines. This efficient method provides fast access to a variety of structurally diverse pyridine derivatives. The structure of a typical product was confirmed by X‐ray crystallography.
Peptide‐Capped Mesoporous Nanoparticles: Toward a more Efficient Internalization of Alendronate
Authors: Añón Elena , Costero Ana M. , Amorós Pedro , El Haskouri Jamal , Martínez‐Mánez Ramón , Parra Margarita , Gil Salvador , Gaviña Pablo , Terencio M. Carmen , Alfonso María
Published: March 2020

Osteoporosis is an illness which appears when the osteoblast/osteoclast activities are unbalanced taking place bone resorption (caused by osteoclasts) in higher extension than bone formation (induced by osteoblasts). Alendronate is one of the most used drugs for osteoporosis treatment despite its scarce bioavailability. Here we present the synthesis and characterization of mesoporous gated nanoparticles (two sets) for the controlled release of alendronate. The first set of nanoparticles (S1) were loaded with sulforhodamine B and capped with a peptide that could be selectively hydrolyzed by cathepsin K enzyme (overexpressed in osteoclasts). The second set (S2) was functionalized with aminopropyl moieties, loaded with nitrobenzofurazan labelled alendronate and capped with the same peptide. Both nanoparticles were internalized by RAW 264.7 macrophages (which could differentiate in osteoclasts) and were able to release its entrapped cargo in the presence of cathepsin K added in the macrophage lysates. Using S2 nanoparticles 4.2% of the total alendronate amount in contact with the cells is liberated inside them and could produce its therapeutic effect.
One‐Pot Synthesis of Densely Substituted 1,2,3,4‐Tetrahydro‐1,6‐naphthyridine Mediated by Isocyanide‐Assisted Reduction of C−C Double Bond
Authors: Das Paramita , Ray Suman , Saha Rupak , Mukhopadhyay Chhanda
Published: March 2020

Molecular architectures possessing the combination of heteroaromatic and saturated N‐heterocycles are of great importance because of their higher solubility in the gastrointestinal tract due to weak crystal packing in the three‐dimensional structure. Other biological activity like selectivity is also increased in a positive way. However, compared to fully aromatic fused heterocycles, synthesis of partially saturated fused heterocycles is much more difficult since the later needs greater control over the reaction conditions. In this context, 1,2,3,4‐tetrahydronaphthyridines (THNADs) are essential part of pharmaceutically important natural products and drug molecules. However, the synthesis of THNAD is seldom reported in literature. To the best of our knowledge, this is the first report of metal‐free one pot synthesis of 1,2,3,4‐tetrahydro‐1,6‐naphthyridines without starting from any nitrogen heterocycles in water. Moreover, this study discloses the involvement of isocyanide in a chemical reaction whose net effect is only to reduce a C=C bond which is unusual in isocyanide literature.
Batch and Column Arsenate Sorption Using Turbinaria ornata Seaweed Derived Biochar: Experimental Studies and Mathematical Modeling
Authors: Saravanakumar Krishnan , Senthilkumar Ramalingham , Prasad Donipathi Mogili Reddy , Prasad Balakrishna Sankari Naveen , Manickam Sathyamoorthy , Gajendiran Vasu
Published: March 2020

The ability of Turbinaria ornata seaweed derived biochar (TOB) to remove arsenate ions from polluted solutions in batch and column trials has been investigated. The biochar, produced at 300 °C and 120 min through pyrolysis, exhibited maximum arsenate sorption capacity at pH 4. Batch sorption isotherm was described with different models (Freundlich, Langmuir and Sips) and the Sips model best described the experimentally derived isotherm with high correlation coefficient and low percentage error values. The maximum arsenate sorptional capacity calculated using the Langmuir model was estimated to be 0.124 mmol/g (at pH 4; 2 g/L biochar dosage and 0.5 mmol/L initial arsenate concentration). For elution trials, 0.01 M NaOH performed well to desorb arsenate from arsenate‐bounded TOB with elution efficiency greater than 99.6% with no significant damage to TOB. The capability of TOB to sorb arsenate continuously was examined in a packed column. The continuous trials were mainly performed to evaluate the impact of influential column parameters including bed height, initial arsenate concentration and flow rate. The arsenate sorptional capacity declined with improvement in flow rate, whereas enhanced with increment in bed depth and initial arsenate concentration values. Regeneration of exhausted TOB was possible with 0.01 M NaOH. After three sorption‐elution cycles it was determined that TOB exhibited superior sorption capacities and percentage removal efficiencies.
From proprietary to collective governance: How do platform participation strategies evolve?
Authors: O'Mahony Siobhan , Karp Rebecca
Published: March 2020

Research Summary

When platform leaders change the rules guiding who can access and control a platform, the strategies of those who create value from the platform can be upended. Little research examines how platform participants adapt their strategies when a platform leader changes the rules governing access and control. We trace how participation with a development platform evolved under four different governance modes with varied access and control conditions. Participation intensity increased as access opened but decreased when platform leadership became unclear. Distributed platform leadership emerged only once the platform was collectively governed. Rather than assume that all firm participation complements a platform, we show how firms guardedly participate with open and collective platforms in ways that can either extend or subvert a platform's vitality.

Managerial Summary

As firms consider transitioning proprietary products to more open platforms to grow market share and relevance, we suggest that managers consider the concerns of external participants when designing a system to govern a platform. Opening access to a platform alone may be insufficient to stimulate external participants to contribute and make real commitments. Our research shows that open access did not stimulate external participation when platform leadership was not clear. When a structured but collectively determined development and governance process was created, external participants increased their contributions and even took on project leadership roles—distributing leadership of the platform among many firms.
Portfolio configuration and foreign entry decisions: A juxtaposition of real options and risk diversification theories
Authors: Belderbos René , Tong Tony W. , Wu Shubin
Published: March 2020

Research Summary

Research on foreign market entry has rarely considered that multinational firms' new entries may be affected by the configuration of their existing affiliates. We argue that in making entry decisions, firms take into account how an entry into a new location helps increase the operational flexibility of their affiliate portfolios due to options to switch operations across affiliates in case of diverging labor cost developments across host countries. We juxtapose this real options‐based explanation with a risk diversification explanation. Analysis of Japanese multinational firms' foreign entry decisions suggests that the two explanations are complementary. We also establish portfolio‐level boundary conditions to the influence of operational flexibility considerations on entry, in the form of product diversification and the nature of dispersion of labor cost levels.

Managerial Summary

When deciding on whether to enter a foreign market, managers of a multinational firm are intuitively aware that they need to consider how the economic environment of the target host country is related to the environments of the existing countries in which the firm operates. The less the environments are correlated with each other, whether in terms of input cost or market demand conditions, the greater the chance that the firm may capture cost savings and reduce sales volatility globally. These benefits arise from a switching option to shift operations flexibly across countries and from an ability to reduce risk by holding a portfolio of diversified global investments. Our findings support both sets of considerations, suggesting that companies do give due attention to correlations in labor cost and market demand between the target host country to enter and the existing host countries.