bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel de novo PDE4D gene mutation identified in a Chinese patient with acrodysostosis
Authors: Zhan Yongkun , Chen Weicheng , Feng Zhiyu , Tan Chaozhong , Li Mengru , Song Yangliu , Zhao Zhengshan , Sheng Wei , Huang Guoying
Published: September 2019

Acrodysostosis is an extremely rare disorder at birth, that is, characterized by skeletal dysplasia with short stature and midfacial hypoplasia, which has been reported to be caused by PDE4D and PRKAR1A gene mutations. Here, a Chinese boy with acrodysostosis, ventricular septal defect, and pulmonary hypertension was recruited for our study, and his clinical and biochemical characteristics were analyzed. A novel de novo heterozygous missense mutation (NM_001104631: c.2030A>C, p.Tyr677Ser) of the PDE4D gene was detected by whole exome sequencing and confirmed by Sanger sequencing. The c.2030A>C (p.Tyr677Ser) variant was located in exon 15 of the PDE4D gene, predicted to be damaging by a functional prediction program and shown to be highly conserved among many species. Further functional analysis showed that the p.Tyr677Ser substitution changes the function of the PDE4D protein, affects its subcellular localization in transfected cells, increases PDE4 activity in the regulation of cAMP signaling and affects cell proliferation. Our study identified a novel de novo PDE4D mutation in acrodysostosis of Chinese origin that not only contributes a deeper appreciation of the phenotypic characteristics of patients with PDE4D mutations but also expands the spectrum of PDE4D mutations.
Foraging ecology drives social information reliance in an avian eavesdropping community
Authors: Jones Harrison H. , Sieving Kathryn E.
Published: September 2019

Vertebrates obtain social information about predation risk by eavesdropping on the alarm calls of sympatric species. In the Holarctic, birds in the family Paridae function as sentinel species; however, factors shaping eavesdroppers' reliance on their alarm calls are unknown. We compared three hypothesized drivers of eavesdropper reliance: (a) foraging ecology, (b) degree of sociality, and (c) call relevance (caller‐to‐eavesdropper body‐size difference). In a rigorous causal‐comparative design, we presented Tufted Titmouse (Baeolophus bicolor) alarm calls to 242 individuals of 31 ecologically diverse bird species in Florida forests and recorded presence/absence and type (diving for cover or freezing in place) of response. Playback response was near universal, as individuals responded to 87% of presentations (N = 211). As an exception to this trend, the sit‐and‐wait flycatcher Eastern Phoebe (Sayornis phoebe) represented 48% of the nonresponses. We tested 12 predictor variables representing measures relevant to the three hypothesized drivers, distance to playback speaker, and vulnerability at time of playback (eavesdropper's microhabitat when alarm call is detected). Using model‐averaged generalized linear models, we determined that foraging ecology best predicted playback response, with aerial foragers responding less often. Foraging ecology (distance from trunk) and microhabitat occupied during playback (distance to escape cover) best predicted escape behavior type. We encountered a sparsity of sit‐and‐wait flycatchers (3 spp.), yet their contrasting responses relative to other foraging behaviors clearly identified foraging ecology as a driver of species‐specific antipredator escape behavior. Our findings align well with known links between the exceptional visual acuity and other phenotypic traits of flycatchers that allow them to rely more heavily on personal rather than social information while foraging. Our results suggest that foraging ecology drives species‐specific antipredator behavior based on the availability and type of escape cover.
Development of a CE‐MS method for the study of riociguat and metabolite M1 in pharmaceutical analysis
Authors: Štícha Martin , Hložek Tomáš , Bursová Miroslava , Čabala Radomír , Jelínek Ivan
Published: September 2019

Riociguat is a novel antihypertensive drug for the treatment of pulmonary hypertension. We present electrophoretic characterization, i.e. migration behavior of riociguat and metabolite M1 as support for optimized CZE/MS assay. Fundamental separation parameters, such as peak width, symmetry, and resolution are studied in a series of ammonium formate buffers within pH range 2.60–5.61. The narrow region of peak symmetry lies close to pH 4.0 for both analytes. Accordingly, the value of resolution maximizes in a background electrolyte adjusted to pH 4.10. Basic calibration parameters estimated from CZE experiments with absorption photometric and mass spectrometric detection of riociguat and metabolite M1 were evaluated. More than three orders lower LOD was achieved with high resolution mass spectrometric detection. The observed difference in the sensitivity of both detection techniques gives priority to the utilization of CZE/MS in practice. The values of dissociation constants of riociguat and metabolite M1, pKBH, were determined from CZE measurements in lithium formate and lithium acetate background electrolytes with constant ionic strength. The value of pKBH = 4.30 ± 0.02 for riociguat corresponds well to the value already presented in the literature. According to our observation, metabolite M1 behaves like a slightly stronger base with estimated pKBH = 4.40 ± 0.02.
Determinants and outcome of repeat continuous electroencephalogram monitoring—A case‐control study
Authors: Punia Vineet , Zawar Ifrah , Briskin Isaac , Burgess Richard , Newey Christopher R. , Hantus Stephen
Published: September 2019

Objective

A retrospective, single‐center study to analyze the determinants of a repeat continuous EEG (cEEG) monitoring during hospitalization and its outcomes using a matched case‐control study design.

Methods

Adults with a repeat cEEG session (cases) were matched by age (±3 years), gender, and mental status to patients with a single cEEG (controls) during hospitalization. Several clinical and EEG characteristics were analyzed to identify predictors of repeat cEEG. Repeat cEEG outcomes were analyzed based on its yield of electrographic seizure. We investigated the predictors of finding increased epileptic potential (degree of association with electrographic seizures) on the repeat cEEG, a marker for possible anti‐epileptic drugs (AEDs) management change.

Results

A total of 213 (8.6% of all unique cEEG patients) cases were included. A multivariable conditional logistic regression model comparing cases and controls showed that the presence of acute brain insult [odds ratio (OR) = 3.36, 95% CI = 1.26‐8.94, P = .015], longer hospital admission (OR = 1.11, 95% CI = 1.07‐1.15, P < .001) and being on AEDs at the end of index cEEG (OR = 4.0, 95% CI = 1.8‐8.87, P < .001) was determinants of a repeat cEEG. Among cases, 17 (8%) had electrographic seizures on repeat cEEG. Increased epileptic potential on repeat cEEG was noted in 34 (16%) cases. The latter is associated with change in etiology after the index cEEG (P = .03) and duration of repeat cEEG (P = .003) based on multivariable logistic regression model. AEDs were changed in 46 (21.6%) patients based on repeat cEEG findings.

Significance

Repeat cEEG is not an uncommon practice. It leads to the diagnosis of electrographic seizures in a significant percentage of patients. With the potential of impacting AED management in 16%‐21% patients, it should be considered in high‐risk patients suffering acute brain insults undergoing prolonged hospitalization.
Indium‐rich InGaN/GaN solar cells with improved performance due to plasmonic and dielectric nanogratings
Authors: Kumawat Uttam K. , Kumar Kamal , Bhardwaj Priyanka , Dhawan Anuj
Published: September 2019

In this study, we propose an indium‐rich InGaN/GaN p‐i‐n thin‐film solar cell which incorporates a dual nanograting (NG) structure: Ag nanogratings (Ag‐NGs) on the backside of the solar cell and gallium nitride nanogratings (GaN‐NGs) on the frontside. Finite‐difference time‐domain (FDTD) simulation results show that the dual NG structure couples the incident sunlight to the plasmonic and photonic modes, thereby increasing the absorption of the solar cell in a broad spectral range. It is observed that the solar cells having the dual nanograting structures have a significant enhancement in light absorption as compared to cells having either no nanogratings or having only the frontside nanogratings or only the backside nanogratings. Analysis of light absorption in solar cells containing the dual NG structures showed that the absorption enhancement of longer wavelengths is mostly due to the Ag‐NGs on the backside and of shorter wavelengths is mostly due to the GaN‐NGs on frontside of the solar cell. The Jsc and power conversion efficiency (PCE) are calculated under AM1.5G solar illumination and are observed to be significantly enhanced due to the presence of optimized dual NG structures. While there is an increase in Jsc from 17.88 to 23.19 mA/cm2 (~30% enhancement), there is an increase in PCE from 15.49% to 20.24% (~31% enhancement) under unpolarized light (average of TM and TE). Moreover, the study of oblique light incidence shows significantly larger Jsc of the dual nanograting solar cells compared to the cells with no nanogratings.
Population‐wide copy number variation calling using variant call format files from 6,898 individuals
Authors: Png Grace , Suveges Daniel , Park Young‐Chan , Walter Klaudia , Kundu Kousik , Ntalla Ioanna , Tsafantakis Emmanouil , Karaleftheri Maria , Dedoussis George , Zeggini Eleftheria , Gilly Arthur
Published: September 2019

Copy number variants (CNVs) play an important role in a number of human diseases, but the accurate calling of CNVs remains challenging. Most current approaches to CNV detection use raw read alignments, which are computationally intensive to process. We use a regression tree‐based approach to call germline CNVs from whole‐genome sequencing (WGS, >18x) variant call sets in 6,898 samples across four European cohorts, and describe a rich large variation landscape comprising 1,320 CNVs. Eighty‐one percent of detected events have been previously reported in the Database of Genomic Variants. Twenty‐three percent of high‐quality deletions affect entire genes, and we recapitulate known events such as the GSTM1 and RHD gene deletions. We test for association between the detected deletions and 275 protein levels in 1,457 individuals to assess the potential clinical impact of the detected CNVs. We describe complex CNV patterns underlying an association with levels of the CCL3 protein (MAF = 0.15, p = 3.6x10−12) at the CCL3L3 locus, and a novel cis‐association between a low‐frequency NOMO1 deletion and NOMO1 protein levels (MAF = 0.02, p = 2.2x10−7). This study demonstrates that existing population‐wide WGS call sets can be mined for germline CNVs with minimal computational overhead, delivering insight into a less well‐studied, yet potentially impactful class of genetic variant.
Combining sequence data from multiple studies: Impact of analysis strategies on rare variant calling and association results
Authors: Chen Zhongsheng , Boehnke Michael , Fuchsberger Christian
Published: September 2019

Individual sequencing studies often have limited sample sizes and so limited power to detect trait associations with rare variants. A common strategy is to aggregate data from multiple studies. For studying rare variants, jointly calling all samples together is the gold standard strategy but can be difficult to implement due to privacy restrictions and computational burden. Here, we compare joint calling to the alternative of single‐study calling in terms of variant detection sensitivity and genotype accuracy as a function of sequencing coverage and assess their impact on downstream association analysis. To do so, we analyze deep‐coverage (~82×) exome and low‐coverage (~5×) genome sequence data on 2,250 individuals from the Genetics of Type 2 Diabetes study jointly and separately within five geographic cohorts.

For rare single nucleotide variants (SNVs): (a) ≥97% of discovered SNVs are found by both calling strategies; (b) nonreference concordance with a set of highly accurate genotypes is ≥99% for both calling strategies; (c) meta‐analysis has similar power to joint analysis in deep‐coverage sequence data but can be less powerful in low‐coverage sequence data. Given similar data processing and quality control steps, we recommend single‐study calling as a viable alternative to joint calling for analyzing SNVs of all minor allele frequency in deep‐coverage data.
P2Y13 receptors regulate microglial morphology, surveillance, and resting levels of interleukin 1β release
Authors: Kyrargyri Vasiliki , Madry Christian , Rifat Ali , Arancibia‐Carcamo I. Lorena , Jones Steffan P. , Chan Victor T. T. , Xu Yajing , Robaye Bernard , Attwell David
Published: September 2019

Microglia sense their environment using an array of membrane receptors. While P2Y12 receptors are known to play a key role in targeting directed motility of microglial processes to sites of damage where ATP/ADP is released, little is known about the role of P2Y13, which transcriptome data suggest is the second most expressed neurotransmitter receptor in microglia. We show that, in patch‐clamp recordings in acute brain slices from mice lacking P2Y13 receptors, the THIK‐1 K+ current density evoked by ADP activating P2Y12 receptors was increased by ~50%. This increase suggested that the P2Y12‐dependent chemotaxis response should be potentiated; however, the time needed for P2Y12‐mediated convergence of microglial processes onto an ADP‐filled pipette or to a laser ablation was longer in the P2Y13 KO. Anatomical analysis showed that the density of microglia was unchanged, but that they were less ramified with a shorter process length in the P2Y13 KO. Thus, chemotactic processes had to grow further and so arrived later at the target, and brain surveillance was reduced by ~30% in the knock‐out. Blocking P2Y12 receptors in brain slices from P2Y13 KO mice did not affect surveillance, demonstrating that tonic activation of these high‐affinity receptors is not needed for surveillance. Strikingly, baseline interleukin‐1β release was increased fivefold while release evoked by LPS and ATP was not affected in the P2Y13 KO, and microglia in intact P2Y13 KO brains were not detectably activated. Thus, P2Y13 receptors play a role different from that of their close relative P2Y12 in regulating microglial morphology and function.
Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer's disease and mild cognitive impairment
Authors: Chandra Avinash , Valkimadi Polytimi‐Eleni , Pagano Gennaro , Cousins Oliver , Dervenoulas George , Politis Marios ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: September 2019

Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease for which there is no cure. Mild cognitive impairment (MCI) is considered a prodromal stage of the disease. Molecular imaging with positron emission tomography (PET) allows for the in vivo visualisation and tracking of pathophysiological changes in AD and MCI. PET is a very promising methodology for differential diagnosis and novel targets of PET imaging might also serve as biomarkers for disease‐modifying therapeutic interventions. This review provides an overview of the current status and applications of in vivo molecular imaging of AD pathology, specifically amyloid, tau, and microglial activation. PET imaging studies were included and evaluated as potential biomarkers and for monitoring disease progression. Although the majority of radiotracers showed the ability to discriminate AD and MCI patients from healthy controls, they had various limitations that prevent the recommendation of a single technique or tracer as an optimal biomarker. Newer research examining amyloid, tau, and microglial PET imaging in combination suggest an alternative approach in studying the disease process.
The importance of different learning stages for motor sequence learning after stroke
Authors: Dahms Christiane , Brodoehl Stefan , Witte Otto W. , Klingner Carsten M.
Published: September 2019

The task of learning predefined sequences of interrelated motor actions is of everyday importance and has also strong clinical importance for regaining motor function after brain lesions. A solid understanding of sequence learning in stroke patients can help clinicians to optimize and individualize rehabilitation strategies. Moreover, to investigate the impact of a focal lesion on the ability to successfully perform motor sequence learning can enhance our comprehension of the underlying physiological principles of motor sequence learning. In this article, we will first provide an overview of current concepts related to motor sequence learning in healthy subjects with focus on the involved brain areas and their assumed functions according to the temporal stage model. Subsequently, we will consider the question of what we can learn from studies investigating motor sequence learning in stroke patients. We will first focus on the implications of lesion location. Then, we will analyze whether distinct lesion locations affect specific learning stages. Finally, we will discuss the implications for clinical rehabilitation and suggest directions for further research.
Positron emission tomography visualized stimulation of the vestibular organ is localized in Heschl's gyrus
Authors: Devantier Louise , Hansen Allan K. , Mølby‐Henriksen Jens‐Jacob , Christensen Christian B. , Pedersen Michael , Hansen Kim V. , Magnusson Måns , Ovesen Therese , Borghammer Per
Published: September 2019

The existence of a human primary vestibular cortex is still debated. Current knowledge mainly derives from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) acquisitions during artificial vestibular stimulation. This may be problematic as artificial vestibular stimulation entails coactivation of other sensory receptors. The use of fMRI is challenging as the strong magnetic field and loud noise during MRI may both stimulate the vestibular organ. This study aimed to characterize the cortical activity during natural stimulation of the human vestibular organ. Two fluorodeoxyglucose (FDG)‐PET scans were obtained after natural vestibular stimulation in a self‐propelled chair. Two types of stimuli were applied: (a) rotation (horizontal semicircular canal) and (b) linear sideways movement (utriculus). A comparable baseline FDG‐PET scan was obtained after sitting motion‐less in the chair. In both stimulation paradigms, significantly increased FDG uptake was measured bilaterally in the medial part of Heschl's gyrus, with some overlap into the posterior insula. This is the first neuroimaging study to visualize cortical processing of natural vestibular stimuli. FDG uptake was demonstrated in the medial‐most part of Heschl's gyrus, normally associated with the primary auditory cortex. This anatomical localization seems plausible, considering that the labyrinth contains both the vestibular organ and the cochlea.
Paneth Cell Dysfunction Mediates Alcohol‐related Steatohepatitis Through Promoting Bacterial Translocation in Mice: Role of Zinc Deficiency
Authors: Zhong Wei , Wei Xiaoyuan , Hao Liuyi , Lin Tai‐Du , Yue Ruichao , Sun Xinguo , Guo Wei , Dong Haibo , Li Tianjiao , Ahmadi Ali R. , Sun Zhaoli , Zhang Qibin , Zhao Jiangchao , Zhou Zhanxiang
Published: September 2019

Background and Aims

Microbial dysbiosis is associated with alcohol‐related hepatitis (AH), with the mechanisms yet to be elucidated. The present study aimed to determine the effects of alcohol and zinc deficiency on Paneth cell (PC) antimicrobial peptides, α‐defensins, and to define the link between PC dysfunction and AH.

Approach and Results

Translocation of pathogen‐associated molecular patterns (PAMPs) was determined in patients with severe AH and in a mouse model of alcoholic steatohepatitis. Microbial composition and PC function were examined in mice. The link between α‐defensin dysfunction and AH was investigated in α‐defensin‐deficient mice. Synthetic human α‐defensin 5 (HD5) was orally given to alcohol‐fed mice to test the therapeutic potential. The role of zinc deficiency in α‐defensin was evaluated in acute and chronic mouse models of zinc deprivation. Hepatic inflammation was associated with PAMP translocation and lipocalin‐2 (LCN2) and chemokine (C‐X‐C motif) ligand 1 (CXCL1) elevation in patients with AH. Antibiotic treatment, lipopolysaccharide injection to mice, and in vitro experiments showed that PAMPs, but not alcohol, directly induced LCN2 and CXCL1. Chronic alcohol feeding caused systemic dysbiosis and PC α‐defensin reduction in mice. Knockout of functional α‐defensins synergistically affected alcohol‐perturbed bacterial composition and the gut barrier and exaggerated PAMP translocation and liver damage. Administration of HD5 effectively altered cecal microbial composition, especially increased Akkermansia muciniphila, and reversed the alcohol‐induced deleterious effects. Zinc‐regulated PC homeostasis and α‐defensins function at multiple levels, and dietary zinc deficiency exaggerated the deleterious effect of alcohol on PC bactericidal activity.

Conclusions

Taken together, the study suggests that alcohol‐induced PC α‐defensin dysfunction is mediated by zinc deficiency and involved in the pathogenesis of AH. HD5 administration may represent a promising therapeutic approach for treating AH.
Engineered Anti‐GPC3 Immunotoxin, HN3‐ABD‐T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention
Authors: Fleming Bryan D. , Urban Daniel J. , Hall Matthew D. , Longerich Thomas , Greten Tim F. , Pastan Ira , Ho Mitchell
Published: September 2019

Background and Aims

Treatment of hepatocellular carcinomas using our glypican‐3 (GPC3)‐targeting human nanobody (HN3) immunotoxins causes potent tumor regression by blocking protein synthesis and down‐regulating the Wnt signaling pathway. However, immunogenicity and a short serum half‐life may limit the ability of immunotoxins to transition to the clinic.

Approach and Results

To address these concerns, we engineered HN3‐based immunotoxins to contain various deimmunized Pseudomonas exotoxin (PE) domains. This included HN3‐T20, which was modified to remove T‐cell epitopes and contains a PE domain II truncation. We compared them to our previously reported B‐cell deimmunized immunotoxin (HN3‐mPE24) and our original HN3‐immunotoxin with a wild‐type PE domain (HN3‐PE38). All of our immunotoxins displayed high affinity to human GPC3, with HN3‐T20 having a KD value of 7.4 nM. HN3‐T20 retained 73% enzymatic activity when compared with the wild‐type immunotoxin in an adenosine diphosphate–ribosylation assay. Interestingly, a real‐time cell growth inhibition assay demonstrated that a single dose of HN3‐T20 at 62.5 ng/mL (1.6 nM) was capable of inhibiting nearly all cell proliferation during the 10‐day experiment. To enhance HN3‐T20’s serum retention, we tested the effect of adding a streptococcal albumin‐binding domain (ABD) and a llama single‐domain antibody fragment specific for mouse and human serum albumin. For the detection of immunotoxin in mouse serum, we developed a highly sensitive enzyme‐linked immunosorbent assay and found that HN3‐ABD‐T20 had a 45‐fold higher serum half‐life than HN3‐T20 (326 minutes vs. 7.3 minutes); consequently, addition of an ABD resulted in HN3‐ABD‐T20–mediated tumor regression at 1 mg/kg.

Conclusion

These data indicate that ABD‐containing deimmunized HN3‐T20 immunotoxins are high‐potency therapeutics ready to be evaluated in clinical trials for the treatment of liver cancer.
Automated detection of calcified plaque using higher‐order spectra cumulant technique in computer tomography angiography images
Authors: Acharya U Rajendra , Meiburger Kristen M. , Koh Joel E. W. , Ciaccio Edward J. , Vicnesh Jahmunah , Tan Sock K. , Wong Jeannie H. D. , Aman Raja R. A. R. , Ng Kwan H.
Published: September 2019

Cardiovascular disease continues to be the leading cause of death globally. Often, it stems from atherosclerosis, which can trigger substantial variations in the coronary arteries, possibly causing coronary artery disease (CAD). Coronary artery calcification is known to be a strong and independent forecaster of CAD. Hence, coronary computer tomography angiography (CTA) has become a fundamental noninvasive imaging tool to characterize coronary artery plaques. In this article, an automated algorithm is presented to uncover the presence of a calcified plaque, using 2060 CTA images acquired from 60 patients. Higher‐order spectra cumulants were extracted from each image, thereby providing 2448 descriptive features per image. The features were then reduced using numerous well‐established techniques, and ranked according to t value. Subsequently, the reduced features were input to several classifiers to achieve the best diagnostic accuracy with a minimum number of features. Optimal results were obtained using the support vector machine with a radial basis function, having 22 features obtained with the multiple factor analysis feature reduction algorithm. The accuracy, positive predictive value, sensitivity, and specificity obtained were 95.83%, 97.05%, 94.54%, and 97.13%, respectively. Based on these results, the technique could be useful to automatically and accurately identify calcified plaque evident in CTA images, and may therefore become an important tool to help reduce procedural costs and patient radiation dose.
Diffusion MRI of the breast: Current status and future directions
Authors: Iima Mami , Honda Maya , Sigmund Eric E. , Ohno Kishimoto Ayami , Kataoka Masako , Togashi Kaori
Published: September 2019

Diffusion‐weighted imaging (DWI) is increasingly being incorporated into routine breast MRI protocols in many institutions worldwide, and there are abundant breast DWI indications ranging from lesion detection and distinguishing malignant from benign tumors to assessing prognostic biomarkers of breast cancer and predicting treatment response. DWI has the potential to serve as a noncontrast MR screening method. Beyond apparent diffusion coefficient (ADC) mapping, which is a commonly used quantitative DWI measure, advanced DWI models such as intravoxel incoherent motion (IVIM), non‐Gaussian diffusion MRI, and diffusion tensor imaging (DTI) are extensively exploited in this field, allowing the characterization of tissue perfusion and architecture and improving diagnostic accuracy without the use of contrast agents. This review will give a summary of the clinical literature along with future directions.

Level of Evidence: 5

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2020;52:70–90.
Tutorial and comprehensive computational study of acceptance and transmission of sinusoidal and digital ion guides
Authors: Huntley Adam P. , Brabeck Gregory F. , Reilly Peter T.A.
Published: September 2019

A quadrupoles acceptance is a measure of its ability to catch ions with certain trajectories. One way to calculate acceptance is the method of ellipses. The method arose partly from a simplification that trajectories could be calculated for an electrode axis independently of others. It has been used to calculate the acceptance and transmission of sine‐driven quadrupole mass filters for over 50 years. Although the method is straightforward, it is generally described with little detail or presented as a confusing string of equations. As such, it may not be decipherable by all practitioners. For this reason, the first half of this paper presents a practical explanation of the method of ellipses and the concepts that make it work. Only equations necessary to describe the method are introduced. The tutorial also prepares the reader for the second half, which presents an alternative approach for calculating acceptance based on an array of initial trajectories. The alternative approach is used to compare the acceptance of simplified sinusoidal and digital ion guides. The method of ellipses was applied to validate results of the new approach for calculation of acceptance.
MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies
Authors: Plachel Fabian , Heuberer Philipp , Gehwolf Renate , Frank Julia , Tempfer Herbert , Lehner Christine , Weissenbacher Nadja , Wagner Andrea , Weigl Moritz , Moroder Philipp , Hackl Matthias , Traweger Andreas
Published: September 2019

MicroRNAs (miRNAs) have emerged as key regulators orchestrating a wide range of inflammatory and fibrotic diseases. However, the role of miRNAs in degenerative shoulder joint disorders is poorly understood. The aim of this explorative case‐control study was to identify pathology‐related, circulating miRNAs in patients with chronic rotator cuff tendinopathy and degenerative rotator cuff tears (RCT). In 2017, 15 patients were prospectively enrolled and assigned to three groups based on the diagnosed pathology: (i) no shoulder pathology, (ii) chronic rotator cuff tendinopathy, and (iii) degenerative RCTs. In total, 14 patients were included. Venous blood samples (“liquid biopsies”) were collected from each patient and serum levels of 187 miRNAs were determined. Subsequently, the change in expression of nine candidate miRNAs was verified in tendon biopsy samples, collected from patients who underwent arthroscopic shoulder surgery between 2015 and 2018. Overall, we identified several miRNAs to be progressively deregulated in sera from patients with either chronic rotator cuff tendinopathy or degenerative RCTs. Importantly, for the several of these miRNAs candidates repression was also evident in tendon biopsies harvested from patients who were treated for a supraspinatus tendon tear. As similar expression profiles were determined for tendon samples, the newly identified systemic miRNA signature has potential as novel diagnostic or prognostic biomarkers for degenerative rotator cuff pathologies. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. Inc. J Orthop Res 38:202–211, 2020
Results of the ADHERE upper airway stimulation registry and predictors of therapy efficacy
Authors: Thaler Erica , Schwab Richard , Maurer Joachim , Soose Ryan , Larsen Christopher , Stevens Suzanne , Stevens Damien , Boon Maurits , Huntley Colin , Doghramji Karl , Waters Tina , Kominsky Alan , Steffen Armin , Kezirian Eric , Hofauer Benedikt , Sommer Ulrich , Withrow Kirk , Strohl Kingman , Heiser Clemens
Published: September 2019

Objective/Hypothesis

The ADHERE Registry is a multicenter prospective observational study following outcomes of upper airway stimulation (UAS) therapy in patients who have failed continuous positive airway pressure therapy for obstructive sleep apnea (OSA). The aim of this registry and purpose of this article were to examine the outcomes of patients receiving UAS for treatment of OSA.

Study Design

Cohort Study.

Methods

Demographic and sleep study data collection occurred at baseline, implantation visit, post‐titration (6 months), and final visit (12 months). Patient and physician reported outcomes were also collected. Post hoc univariate and multivariate analysis was used to identify predictors of therapy response, defined as ≥50% decrease in Apnea‐Hypopnea Index (AHI) and AHI ≤20 at the 12‐month visit.

Results

The registry has enrolled 1,017 patients from October 2016 through February 2019. Thus far, 640 patients have completed their 6‐month follow‐up and 382 have completed the 12‐month follow‐up. After 12 months, median AHI was reduced from 32.8 (interquartile range [IQR], 23.6–45.0) to 9.5 (IQR, 4.0–18.5); mean, 35.8 ± 15.4 to 14.2 ± 15.0, P < .0001. Epworth Sleepiness Scale was similarly improved from 11.0 (IQR, 7–16) to 7.0 (IQR, 4–11); mean, 11.4 ± 5.6 to 7.2 ± 4.8, P < .0001. Therapy usage was 5.6 ± 2.1 hours per night after 12 months. In a multivariate model, only female sex and lower baseline body mass index remained as significant predictors of therapy response.

Conclusions

Across a multi‐institutional study, UAS therapy continues to show significant improvement in subjective and objective OSA outcomes. This analysis shows that the therapy effect is durable and adherence is high.

Level of Evidence

2

Laryngoscope, 130:1333–1338, 2020
Theoretical design of eight‐band linear‐to‐circular converter in reflection and transmission modes based on self‐complementary metasurfaces
Authors: Zhang Xiangjun , Li Sijie
Published: September 2019

Multiband linear‐to‐circular (LTC) metamaterial converters have promising applications in modern optical system. However, it is challenging to design a converter with conversion bands of more than four and the axial ratio of less than 3 dB due to the coupling interaction of different resonant structures in a unit cell. In this article, we demonstrate a broad class of self‐complementary THz infinite thin metasurfaces composed of supercells of fractal metal rectangular patches and holes dimers of spanning 1 THz octave in bandwidth, while still being highly efficient. The advantages of this converter are as follows. The device is theoretically nonthickness; the LTC polarization conversion can be achieved in both the reflected and transmitted fields; the phase difference between two orthogonal linear polarization components is theoretically 90° in any frequency. Therefore, an eight‐band LTC converter is achieved in reflection and transmission modes. This new nonthickness multiband device will demonstrate a major advance toward an LTC synthetic metasurface in the THz band.
Integrated filtering duplex patch antenna with small frequency ratio and high isolation
Authors: Lin Xian‐Jing , Zhang Yao , Xie Ze‐Ming
Published: September 2019

An integrated filtering duplex antenna with small frequency ratio and high isolation is proposed in this article. First, a small transmitter‐receiver frequency ratio of stacked patch antenna is realized by soldering short circuit chips to the driven patch. Then, the asymmetric transmission zero technology is employed in the sets of dual‐mode resonators to realize high port‐to‐port isolation. Moreover, the ports coupling mode of the dual‐mode resonator is changed to achieve further Tx‐Rx isolation. For demonstration, the proposed antenna is fabricated and experimentally characterized in WCDMA band. The measured results show that it can mainly operate over the uplink and downlink operation band of WCDMA with an isolation level better than 32 dB, and the frequency interval (Δf = (f
r − f
t)) is only 0.09 times of the central frequency ((f
r + f
t)/2).
Adaptive large neighborhood search for the vehicle routing problem with synchronization constraints at the delivery location
Authors: Sarasola Briseida , Doerner Karl F.
Published: September 2019

A vehicle routing problem with synchronization constraints arises in urban freight transportation, in which context customers require deliveries from one or more logistics service providers. These deliveries should be efficient to reduce idle times at the delivery locations. Idle time is defined as nonservice time between the first and the last delivery received by the customer. We propose a strategy which relies on self‐imposed time windows, and we compare our approach with an exact determination of a feasible schedule and fixed time windows. The results show that idle times can be reduced by 54.12%‐79.77%, with an average cost rise of 9.87%. In addition, self‐imposed time windows provide solutions with 15.74%‐21.43% lower costs than feasibility checks for short runtimes and 13.71%‐21.15% lower than fixed time windows.
A novel strategy to reinforce glass fiber fabric/epoxy composites via modifying fibers with self‐assembled multi‐walled carbon nanotubes‐montmorillonite
Authors: Zeng Shaohua , Shen Mingxia , Xue Yijiao , Niu Chenxu , Zheng Yifei , Han Yanxin , Tao Wenzhu , Yang Lu
Published: September 2019

A novel strategy of multi‐walled carbon nanotubes‐montmorillonite (MWCNTs‐Mt)‐modified glass fiber fabrics (GFf) was used here to reinforce interlaminar regions of epoxy composites. One/two‐dimensional MWCNTs‐Mt hybrids with different mass ratios of MWCNTs and Mt were combined with the GFf, respectively, prior to a resin injection process. Making use of this strategy, uniformly dispersed MWCNTs and highly exfoliated Mt at the fiber/matrix interface could be achieved; meanwhile, mechanical and interfacial properties of resultant composites were greatly enhanced. Under a mass ratio of MWCNTs:Mt (0.2:1), the interlaminar shear, tensile, and flexural strengths of resultant composites were improved by 31.0%, 26.0%, and 21.9%, respectively; the storage modulus increased by 23.6%, compared with the composite without MWCNTs‐Mt. Also, the work of fracture obtained from interlaminar load‐displacement curves and peak loss moduli of resultant composites were significantly enhanced, indicating the synergistic toughening effect of MWCNTs and Mt.
Thermomechanical characterization of thermoplastic polyimides to improve the chain collaboration via ureidopyrimidone endcaps
Authors: Nicholls Alejandro Rivera , Perez Yesenia , Pellisier Matthew , Rodde Arnaud , Lanusse Pierre , Stock John Allan , Kull Ken , Eubank Jarrod , Harmon Julie P.
Published: September 2019

In this report, we explored the effect of incorporating ureidopyrimidone (UPy) linkers in a series of polyimides (PIs) previously studied in our laboratory. The polymers consist of an aromatic diamine monomer with a methylene linker, 4,4′’‐methylenebis (2,6‐dimethylaniline), used to make a robust main chain along with aliphatic polyetherdiamine backbone linkers to decrease rigidity. The polymers were designed to exhibit thermal properties in between those of conventional aromatic PIs and polymers with wholly aliphatic ether diamine links, with an aim to improve the mechanical characteristics. Through dynamic mechanical analysis and differential scanning calorimetry, it is shown that the UPy linkers with their four‐hydrogen bond sites are introduced to connect the chains in series. The connection strengthens the chain interactions and increases the range of the thermal and mechanical properties of the PI. Furthermore, the connecting regions are an important component to preserve the thermal stability of PIs while maintaining the processability. The polymers were characterized by FTIR, nuclear magnetic resonance, GPC, thermogravimetric analysis, differential scanning calorimetry, dynamic mechanical analysis, microhardness, and tensile testing. POLYM. ENG. SCI., 59:2231–2246, 2019. © 2019 Society of Plastics Engineers
Facile synthesis of graft copolymers containing rigid poly(dialkyl fumarate) branches by macromonomer method
Authors: Sato Eriko , Tamari Noboru , Horibe Hideo
Published: September 2019

Graft copolymers show microphase separated structure as seen in block copolymers and have lower intrinsic viscosity than block copolymers because of a branching structure. Therefore, considering molding processability, especially for polymers containing rigid segments, graft copolymers are useful architectures. In this work, graft copolymers containing rigid poly(diisopropyl fumarate) (PDiPF) branches were synthesized by full free‐radical polymerization process. First, synthesis of PDiPF macromonomers by addition‐fragmentation chain transfer (AFCT) was investigated. 2,2‐Dimethyl‐4‐methylene‐pentanedioic acid dimethyl ester was found to be an efficient AFCT agent for diisopropyl fumarate (DiPF) polymerization because of the suppression of undesired primary radical termination, which significantly took place when common AFCT agent, methyl 2‐(bromomethyl)acrylate, was used. Copolymerization of PDiPF macromonomer with ethyl acrylate accomplished the generation of the graft copolymer having flexible poly(ethyl acrylate) backbone and rigid PDiPF branches. The graft copolymer showed a microphase separated structure, high transparency, and characteristic thermal properties to PDiPF and poly(ethyl acrylate). © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2474–2480
Feasibility and acceptability of using an IVRS to assess decision making about sun protection
Authors: Holland Susan M. , Shuk Elyse , Burkhalter Jack , Shouery Marwan , Li Yuelin , Hay Jennifer L.
Published: September 2019

Objective

We developed an interactive voice response system (IVRS), an automated telephone survey technology, to assess real‐time decision making about sun protection. We examined the feasibility and acceptability of IVRS in this electronic health (eHealth) context.

Methods

Melanoma patients who underwent surgery referred their first‐degree relatives (FDRs) for participation. Eligible FDRs were contacted twice daily (12:30 pm; 5:00 pm) over 14 consecutive days via IVRS to complete a survey about their sun protection behaviors and decisions about those behaviors.

Results

Of the 81 eligible FDRs, 69 (85%) consented to the study, and 53 (77%) completed the study. We assessed adherence with the IVRS via the number and pattern of missing survey items across all answered IVRS calls. About 80% of scheduled IVRS calls were answered (1316/1652). Most surveys (93%) of the IVRS‐answered calls were completed. To examine acceptability, we analyzed the program satisfaction survey data collected at the end of the study. Most participants viewed the IVRS to be highly acceptable and easy to use.

Conclusions

These findings illustrate that use of real‐time IVRS data collection regarding sun protection decision making is feasible and acceptable to higher‐risk research participants and could thus be used with time and location‐sensitive eHealth support to enhance sun protection decision making.
Transcriptomic and Proteomic Profiling of Human Mesenchymal Stem Cell Derived from Umbilical Cord in the Study of Preterm Birth
Authors: Chien Chih‐Wei , Lo Yu‐Shu , Wu Hsin‐Yi , Hsuan Yogi , Lin Chi‐Kang , Chen Yu‐Ju , Lin Willie , Han Chia‐Li
Published: September 2019

Objective

Mesenchymal stem cells (MSCs) hold great therapeutic potential in morbidities associated with preterm birth. However, the molecular expressions of MSCs in preterm birth infants are not systematically evaluated. In this study, the dual‐omics analyses of umbilical‐cord (UC)‐derived MSCs to identify the dysregulated cellular functions are presented.

Materials and methods

The UC‐MSCs are collected from ten full‐term and eight preterm birth infants for microarray and iTRAQ‐based proteome profiling.

Results

The integrative analysis of dual‐omics data discovered 5615 commonly identified genes/proteins of which 29 genes/proteins show consistent up‐ or downregulation in preterm birth. The Gene Ontology analysis reveals that dysregulation of mitochondrial translation and cellular response to oxidative stress are mainly enriched in 290 differential expression proteins (DEPs) while the 412 differential expression genes (DEGs) are majorly involved in single‐organism biosynthetic process, cellular response to stress, and mitotic cell cycle in preterm birth. Besides, a 13‐protein module involving CUL2 and CUL3 is identified, which plays an important role in cullin‐RING‐based ubiquitin ligase complex, as potential mechanism for preterm birth.

Conclusion

The dual‐omics data not only provide new insights to the molecular mechanism but also identify panel of candidate markers associated with preterm birth.
Oxygen Affinity of Metal Electrodes as Control Parameter in Tuning the Performance of CuxO‐Based Resistive Random Access Memory Devices
Authors: Sangani Laxmi Dhanaraju Varma , Krishna Mamidipudi Ghanashyam
Published: September 2019

CuxO‐based resistive random access memory (RRAM) devices are fabricated with low, medium, and high oxygen affinity metals as the top electrode and gold and platinum as the bottom electrode. Switching performance of the device with varying oxygen affinity is observed. The variation, mean, and the cycle percentage of Vset and Vreset values decrease with the decrease in oxygen affinity but increase in the case of Ireset. The reset power parameter decreases with oxygen affinity of metal electrodes (OAME). A generalized figure of merit (FM), which considers all the parameters (variation, mean, and cycles count) of a switching parameter (Vset, Vreset, Ireset, and Preset), is introduced to explain the performance. The FM also confirms the variation in switching parameters with oxygen affinity. This reveals that the performance of the device is improved with the decrease in oxygen affinity. The device fabricated with low oxygen affinity metal electrode, Ni, shows the best performance among all the CuxO‐based RRAM devices. Further improvement in device performance is achieved by changing the bottom electrode from Au to Pt with the top electrode being retained as a low oxygen affinity metal. This combination is shown to be the best in terms of retention and endurance.
Improved multiparameter exponential‐type potential for diatomic molecules
Authors: Xie Bin‐Jie , Jia Chun‐Sheng
Published: September 2019

We report an improved multiparameter exponential‐type potential (MPETP) energy model for diatomic molecules. It is found that this potential is identical to the Tietz potential in the realm of diatomic molecules. The efficiency of the improved MPETP is clarified by simulating the internuclear interaction potential curve for the A (3Π1) state of the chlorine monofluoride molecule.
Mechanistic Study of Monolayer NiP2 (100) toward Solar Hydrogen Production
Authors: Hu Jun , Zhao Xin , Chen Wei , Zheng Shunli , Chen Zhong
Published: September 2019

Understanding the catalytic mechanism at the molecular level is critical to the design and exploration of new materials for solar hydrogen production. Herein, the catalytic activity toward hydrogen evolution reaction (HER) is surveyed for all low‐index surfaces of different nickel phosphides (Ni3P, Ni12P5, Ni2P, Ni5P4, NiP, NiP2, and NiP3). It is found that the surface P atoms with only one single PP bond possess excellent HER activity. Accordingly, a monolayer NiP2 (100) is explored as the cathode material. Comprehensive density functional theory study is used to verify the HER activity of this material, including the effect of vacancy and doping. Defect‐free and Zn‐doped monolayer NiP2 (100) are found to possess excellent HER activity and thermodynamic stability. This crystal facet also has a high density of active sites (0.126 N Å−2 under an applied over‐potential of 200 mV), which is very close to the Pt (111) surface (0.132 N Å−2). The low surface energy and strengthened bonding imply that the monolayer NiP2 (100) can be stable and easy to synthesize. This finding not only promotes a comprehensive understanding of NixPy material toward its catalytic activity for HER, but also suggests a possible new material for the experimentalist in the field.
Portraying double Higgs at the Large Hadron Collider
Authors: Kim Jeong Han , Kim Minho , Kong Kyoungchul , Matchev Konstantin T. , Park Myeonghun
Published: September 2019

Abstract

We examine the discovery potential for double Higgs production at the high luminosity LHC in the final state with two b-tagged jets, two leptons and missing transverse momentum. Although this dilepton final state has been considered a difficult channel due to the large backgrounds, we argue that it is possible to obtain sizable signal significance, by adopting a deep learning framework making full use of the relevant kinematics along with the jet images from the Higgs decay. For the relevant number of signal events we obtain a substantial increase in signal sensitivity over existing analyses. We discuss relative improvements at each stage and the correlations among the different input variables for the neutral network. The proposed method can be easily generalized to the semi-leptonic channel of double Higgs production, as well as to other processes with similar final states.