bluuebunny/crossref_metadata_2025_split huggingface dataset:
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/HypothesisThe 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 DesignSingle‐subject design.MethodsTwenty‐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.ResultsFunctional 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.ConclusionsThis 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 Evidence2c 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

AbstractAqueous 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

AbstractThe 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

ABSTRACTBackgroundFragile 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).ObjectiveTo describe the frequency of concomitant PD in FXTAS.MethodsWe reviewed the medical record of 40 deceased patients diagnosed with FXTAS and performed a pathology analysis to confirm both FXTAS and PD.ResultsClinical 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.ConclusionThis 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

AbstractBackgroundPlasma 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.MethodWe 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.ResultsIn 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).ConclusionABCC3 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

AbstractMyotonic 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

SummaryCapturing 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

SummaryModal 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.
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

AbstractPurposeTo examine the RWE U.S. commercial health plans cite in their specialty drug coverage decisions.MethodsWe 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.ResultsRWE 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.ConclusionsHealth 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

AbstractObjectiveChildren 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.DesignSemi‐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.ResultsFifteen 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.ConclusionHospital 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.
Convective organization and eastward propagating equatorial disturbances in a simple excitable system
Authors: Vallis Geoffrey K. , Penn James 
Published: March 2020

AbstractWe 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

AbstractAlzheimer'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

AbstractThe 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.