bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stability of flexible thin-film metallization stimulation electrodes: analysis of explants after first-in-human study and improvement of in vivo performance
Authors: Čvančara Paul , Boretius Tim , López-Álvarez Víctor M , Maciejasz Pawel , Andreu David , Raspopovic Stanisa , Petrini Francesco , Micera Silvestro , Granata Giuseppe , Fernandez Eduardo , Rossini Paolo M , Yoshida Ken , Jensen Winnie , Divoux Jean-Louis , Guiraud David , Navarro Xavier , Stieglitz Thomas 
Published: June 2020

Abstract

Objective. Micro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices. Approach. This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A failure mode analysis on the explanted devices was performed after a first-in-human study limited to 30 d. Main results. About 90% of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5% of the stimulation contacts showed signs of delamination at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions within a rodent animal trial. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface. Significance. Failure mode analysis guided implant stability optimization. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications. (Document number of Ethical Committee: P/905/CE/2012; Date of approval: 2012–10-04)
Facet-driven formation of axial and radial In(Ga)As clusters in GaAs nanowires
Authors: Balgarkashi A , Ramanandan S P , Tappy N , Nahra M , Kim W , Güniat L , Friedl M , Morgan N , Dede D , Leran J B , Couteau C , Fontcuberta i Morral A 
Published: June 2020

Abstract
Embedding quantum dots in nanowires (NWs) constitutes one promising building block for quantum photonic technologies. Earlier attempts to grow InAs quantum dots on GaAs nanowires were based on the Stranski–Krastanov growth mechanism. Here, we propose a novel strain-driven mechanism to form 3D In-rich clusters on the NW sidewalls and also on the NW top facets. The focus is on ternary InGaAs nanowire quantum dots which are particularly attractive for producing single photons at telecommunication wavelengths. In(Ga)As clusters were realized on the inclined top facets and also on the {11-2} corner facets of GaAs NW arrays by depositing InAs at a high growth temperature (630 °C). High-angle annular dark-field scanning transmission electron microscopy combined with energy-dispersive x-ray spectroscopy confirms that the observed 3D clusters are indeed In-rich. The optical functionality of the as-grown samples was verified using optical technique of cathodoluminescence. Emission maps close to the NW tip shows the presence of optically active emission centers along the NW sidewalls. Our work illustrates how facets can be used to engineer the growth of localized emitters in semiconducting NWs.
Psychometric Properties of the Person-Centered Version of the Alcohol and Alcohol Problems Perceptions Questionnaire (PC-AAPPQ)
Authors: Mahmoud Khadejah F , Terhorst Lauren , Lindsay Dawn , Brager Jenna , Rodney Tamar , Sanchez Michael , Hansen Bryan R , Savage Christine L , Seale J Paul , Mitchell Ann M , Johnson J Aaron , Finnell Deborah S 
Published: June 2020

Abstract

Aims
Given the importance of addressing provider attitudes toward individuals with unhealthy alcohol use and the current emphasis on person-centered language to help decrease stigma and mitigate negative attitudes, the aim of this study was to evaluate the psychometric properties of a contemporary version of the Alcohol and Alcohol Problems Perception Questionnaire (AAPPQ) that uses person-centered language and addresses the spectrum of alcohol use.

Methods
The authors created a person-centered version of the AAPPQ (PC-AAPPQ) and conducted a cross-sectional study of its psychometric properties in academic settings in the Northeastern United States. The PC-AAPPQ was administered to 651 nursing students. Reliability analysis of the new instrument was performed using the total sample. Only surveys with complete data (n = 637) were randomly split into two datasets, one used for the exploratory factor analysis (EFA) (n = 310) and the other for confirmatory factor analysis (CFA) (n = 327).

Results
Compared to all the models generated from the EFA, neither the original six-factor structure nor the five-factor structure was superior to any of the other models. The results indicate that a seven-factor structure with all 30 items is the best fit for the PC-AAPPQ.

Conclusions
The PC-AAPPQ represents a positive effort to modernize the four-decade-old AAPPQ. This 30-item instrument, which adds one additional subscale, offers a means to assess providers’ attitudes using respectful wording that avoids perpetuating negative biases and reinforces efforts to affirm the worth and dignity of the population being treated.
Exploring transcriptional switches from pairwise, temporal and population RNA-Seq data using deepTS
Authors: Qiu Zhixu , Chen Siyuan , Qi Yuhong , Liu Chunni , Zhai Jingjing , Xie Shang , Ma Chuang 
Published: June 2020

Abstract
Transcriptional switch (TS) is a widely observed phenomenon caused by changes in the relative expression of transcripts from the same gene, in spatial, temporal or other dimensions. TS has been associated with human diseases, plant development and stress responses. Its investigation is often hampered by a lack of suitable tools allowing comprehensive and flexible TS analysis for high-throughput RNA sequencing (RNA-Seq) data. Here, we present deepTS, a user-friendly web-based implementation that enables a fully interactive, multifunctional identification, visualization and analysis of TS events for large-scale RNA-Seq datasets from pairwise, temporal and population experiments. deepTS offers rich functionality to streamline RNA-Seq-based TS analysis for both model and non-model organisms and for those with or without reference transcriptome. The presented case studies highlight the capabilities of deepTS and demonstrate its potential for the transcriptome-wide TS analysis of pairwise, temporal and population RNA-Seq data. We believe deepTS will help research groups, regardless of their informatics expertise, perform accessible, reproducible and collaborative TS analyses of large-scale RNA-Seq data.
Engineering monoclonal antibody-based contraception and multipurpose prevention technologies†
Authors: Anderson Deborah J , Politch Joseph A , Cone Richard A , Zeitlin Larry , Lai Samuel K , Santangelo Philip J , Moench Thomas R , Whaley Kevin J 
Published: June 2020

AbstractSexually transmitted infections are highly prevalent, and over 40% of pregnancies are unplanned. We are producing new antibody-based multipurpose prevention technology products to address these problems and fill an unmet need in female reproductive health. We used a Nicotiana platform to manufacture monoclonal antibodies against two prevalent sexually transmitted pathogens, HIV-1 and HSV-2, and incorporated them into a vaginal film (MB66) for preclinical and Phase 1 clinical testing. These tests are now complete and indicate that MB66 is effective and safe in women. We are now developing an antisperm monoclonal antibody to add contraceptive efficacy to this product. The antisperm antibody, H6-3C4, originally isolated by Shinzo Isojima from the blood of an infertile woman, recognizes a carbohydrate epitope on CD52g, a glycosylphosphatidylinositol-anchored glycoprotein found in abundance on the surface of human sperm. We engineered the antibody for production in Nicotiana; the new antibody which we call “human contraception antibody,” effectively agglutinates sperm at concentrations &gt;10 μg/ml and maintains activity under a variety of physiological conditions. We are currently seeking regulatory approval for a Phase 1 clinical trial, which will include safety and “proof of principle” efficacy endpoints. Concurrently, we are working with new antibody production platforms to bring the costs down, innovative antibody designs that may produce more effective second-generation antibodies, and delivery systems to provide extended protection.
Biomarkers in psychiatry: a clinician’s viewpoint
Authors: Mahmood Tariq 
Published: June 2020

Abstract

Introduction
The dearth of biomarkers limits the precision of our research into pathogenesis of psychiatric disorders and has slowed down the development of new drugs. In clinical practice, it undermines the validity of psychiatric diagnoses and hampers the delivery of personalized treatment.

Sources of data
The data quoted in this paper are gathered from a range of sources encompassing scientific and journalistic both in print and electronic.

Areas of agreement
Availability of clinically useful biomarkers will improve the prognosis and outcome of psychiatric patients by helping in early diagnosis and delivery of individualized treatment.

Areas of controversy
The cross-sectional and longitudinal observation of psychopathology is the bedrock of current clinical practice. Are psychiatric biomarkers advanced enough to supplant it?

Growing points
The need for biomarkers of psychiatric disorders has become more acute with the advent of new treatments which require precision and an individualized approach.

Areas timely for developing research
Identification and deployment of intermediate phenotypes in classification, research and clinical practice of psychiatry.
Improved relapse recovery in paediatric compared to adult multiple sclerosis
Authors: Chitnis Tanuja , Aaen Greg , Belman Anita , Benson Leslie , Gorman Mark , Goyal Manu S , Graves Jennifer S , Harris Yolanda , Krupp Lauren , Lotze Timothy , Mar Soe , Ness Jayne , Rensel Mary , Schreiner Teri , Tillema Jan-Mendelt , Waubant Emmanuelle , Weinstock-Guttman Bianca , Roalstad Shelly , Rose John , Weiner Howard L , Casper T Charles , Rodriguez Moses ,   for the US Network of Paediatric Multiple Sclerosis Centers
Published: June 2020

AbstractIncomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P &lt; 0.0001). A larger proportion of children versus adults demonstrated improvement in EDSS following an attack (P = 0.006). For every 10 years of age, odds of EDSS not improving increase by 1.33 times (P &lt; 0.0001). Younger age is associated with improved recovery from relapses. Age-related mechanisms may provide novel therapeutic targets for disability accrual in multiple sclerosis.
Gut metagenomics-derived genes as potential biomarkers of Parkinson’s disease
Authors: Qian Yiwei , Yang Xiaodong , Xu Shaoqing , Huang Pei , Li Binyin , Du Juanjuan , He Yixi , Su Binghua , Xu Li-Ming , Wang Liang , Huang Ruocheng , Chen Shengdi , Xiao Qin 
Published: June 2020

Abstract
Identification of the gut microbiome compositions associated with disease has become a research focus worldwide. Emerging evidence has revealed the presence of gut microbiota dysbiosis in Parkinson’s disease. In this study, we aimed to identify the gut microbiome associated with Parkinson’s disease and subsequently to screen and to validate potential diagnostic biomarkers of Parkinson’s disease. This case-control study investigated gut microbial genes in faeces from 40 volunteer Chinese patients with Parkinson’s disease and their healthy spouses using shotgun metagenomic sequencing. Furthermore, the identified specific gut microbial gene markers were validated with real-time PCR in an independent Chinese cohort of 78 Parkinson’s disease patients, 75 control subjects, 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease. We developed the first gut microbial gene catalogue associated with Parkinson’s disease. Twenty-five gene markers were identified that distinguished Parkinson’s disease patients from healthy control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.896 (95% confidence interval: 83.1–96.1%). A highly accurate Parkinson’s disease index, which was not influenced by disease severity or Parkinson’s disease medications, was created. Testing these gene markers using quantitative PCR distinguished Parkinson’s disease patients from healthy controls not only in the 40 couples (AUC = 0.922, 95% confidence interval: 86.4–98.0%), but also in an independent group of 78 patients with Parkinson’s disease and 75 healthy control subjects (AUC = 0.905, 95% confidence interval: 86.0–95.1%). This classifier also performed a differential diagnosis power in discriminating these 78 patients with Parkinson’s disease from a cohort of 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease based on the panel of 25 biomarkers. Based on our results, the identified Parkinson’s disease index based on the gene set from the gut microbiome may be a potential diagnostic biomarker of Parkinson’s disease.
A novel regulatory loop miR-101/ANXA2/EGR1 mediates malignant characteristics of liver cancer stem cells
Authors: Ma Sai , Cheng Junping , Wang Haiyan , Ding Ningling , Zhou Feng , Ji Runing , Zhu Li , Zhu Chuanwu , Pan Yunzhi 
Published: June 2020

Abstract
Increasing evidence suggests that liver cancer stem cells (LCSCs) are the cellular determinants that promote tumor recurrence and metastases. Aberrantly expressed miRNAs were identified in LCSCs and found to play a significant role in modulating biological characteristics of LCSCs. In this study, we implemented miRNA microarrays in CD133+ LCSCs and found miR-101 expression was downregulated. Increasing miR-101 expression repressed the metastasis and tumorigenic potential in LCSCs. Further investigations showed that ANXA2 was a novel target of miR-101. And we revealed that ANXA2 plays a critical role in acceleration of cell cycle and enhancing the migration and invasion abilities of LCSCs. Elevated ANXA2 increased activation of extracellular signal-regulated kinase (ERK) which regulated SOX2 and cell cycle-related kinases. Moreover, ERK phosphorylation inhibited the expression of early growth response 1 (EGR1) which in turn restrained the transcription of miR-101. In vivo experiments, overexpression of miR-101 produced potent inhibitory effects on the growth of LCSCs xenograft tumors as well as ANXA2 knockdown. Taken together, our findings suggest a novel regulatory loop miR-101/ANXA2/EGR1 in LCSCs and may serve as potential therapeutic targets in liver cancer.
DUOX2 promotes the progression of colorectal cancer cells by regulating the AKT pathway and interacting with RPL3
Authors: Zhang Xue , Han Jing , Feng Li , Zhi Lianghui , Jiang Da , Yu Bin , Zhang Zhenya , Gao Bo , Zhang Cong , Li Meng , Zhao Lianmei , Wang Guiying 
Published: June 2020

AbstractDual oxidase 2 (DUOX2) is an important regulatory protein in the organic process of thyroid hormone iodine. Mounting evidence suggests that DUOX2 plays a crucial role in the occurrence and development of cancers. However, the function and mechanism of DUOX2 in colorectal cancer (CRC) have not been fully clarified. In the present study, the relationship between the expression of DUOX2 and the clinicopathological features and prognosis of CRC patients was analyzed. Furthermore, the effects of DUOX2 on proliferation and invasion in vitro and in vivo were examined. DUOX2-associated proteins were identified by immunoprecipitation (IP). Next-generation sequencing detection was performed to illustrate the mechanism of DUOX2 in CRC cells. It was found that the expression levels of DUOX2 in metastatic sites were significantly higher than those in primary tumor tissues, and this was demonstrated to be associated with poor prognosis. The knockdown of DUOX2 inhibited the invasion and migration of CRC cells. Furthermore, DUOX2 regulated the stability of ribosomal protein uL3 (RPL3) by affecting the ubiquitination status of RPL3, and the invasion and migration ability of DUOX2 can be reversed by the overexpression of RPL3. The downregulation of DUOX2 can affect the expression level of a large number of genes, and a number of these are enriched in the PI3K–AKT pathway. Some of the changes caused by DUOX2 can be reversed by RPL3. In summary, DUOX2 exhibits a significantly higher expression in CRC tumor samples, and facilitates the invasion and metastasis ability of CRC cells by interacting with RPL3.
Quantifying Genetic and Environmental Influence on Gray Matter Microstructure Using Diffusion MRI
Authors: Baxi Madhura , Di Biase Maria A , Lyall Amanda E , Cetin-Karayumak Suheyla , Seitz Johanna , Ning Lipeng , Makris Nikos , Rosene Douglas , Kubicki Marek , Rathi Yogesh 
Published: June 2020

Abstract
Early neuroimaging work in twin studies focused on studying genetic and environmental influence on gray matter macrostructure. However, it is also important to understand how gray matter microstructure is influenced by genes and environment to facilitate future investigations of their influence in mental disorders. Advanced diffusion MRI (dMRI) measures allow more accurate assessment of gray matter microstructure compared with conventional diffusion tensor measures. To understand genetic and environmental influence on gray matter, we used diffusion and structural MRI data from a large twin and sibling study (N = 840) and computed advanced dMRI measures including return to origin probability (RTOP), which is heavily weighted toward intracellular and intra-axonal restricted spaces, and mean squared displacement (MSD), more heavily weighted to diffusion in extracellular space and large cell bodies in gray matter. We show that while macrostructural features like brain volume are mainly genetically influenced, RTOP and MSD can together tap into both genetic and environmental influence on microstructure.
Studies of Human Twins Reveal Genetic Variation That Affects Dietary Fat Perception
Authors: Lin Cailu , Colquitt Lauren , Wise Paul , Breslin Paul A S , Rawson Nancy E , Genovese Federica , Maina Ivy , Joseph Paule , Fomuso Lydia , Slade Louise , Brooks Dennis , Miclo Aurélie , Hayes John E , Sullo Antonio , Reed Danielle R 
Published: June 2020

Abstract
To learn more about the mechanisms of human dietary fat perception, we asked 398 human twins to rate the fattiness and how much they liked 6 types of potato chips that differed in triglyceride content (2.5%, 5%, 10%, and 15% corn oil); reliability estimates were obtained from a subset (n = 50) who did the task twice. Some chips also had a saturated long-chain fatty acid (FA; hexadecanoic acid, 16:0) added (0.2%) to evaluate its effect on fattiness and liking. We computed the heritability of these measures and conducted a genome-wide association study (GWAS) to identify regions of the genome that co-segregate with fattiness and liking. Perceived fattiness of and liking for the potato chips were reliable (r = 0.31–0.62, P &lt; 0.05) and heritable (up to h2 = 0.29, P &lt; 0.001, for liking). Adding hexadecanoic acid to the potato chips significantly increased ratings of fattiness but decreased liking. Twins with the G allele of rs263429 near GATA3-AS1 or the G allele of rs8103990 within ZNF729 reported more liking for potato chips than did twins with the other allele (multivariate GWAS, P &lt; 1 × 10–5), with results reaching genome-wide suggestive but not significance criteria. Person-to-person variation in the perception and liking of dietary fat was 1) negatively affected by the addition of a saturated FA and 2) related to inborn genetic variants. These data suggest that liking for dietary fat is not due solely to FA content and highlight new candidate genes and proteins within this sensory pathway.
Transient Effects of Cyclophosphamide on Basal Cell Proliferation of Olfactory Epithelia
Authors: Joseph Kyle B , Awadallah Nora , Delay Eugene R , Delay Rona J 
Published: June 2020

AbstractCancer is often treated with broad-spectrum cytotoxic drugs that not only eradicate cancerous cells but also have detrimental side effects. One of these side effects, disruption of the olfactory system, impedes a patient’s ability to smell, perceive flavor, and ultimately may interfere with their nutritional intake and recovery from cancer. Recent studies reported that the chemotherapy drug, cyclophosphamide (CYP), can damage gustatory epithelia and disrupt cell proliferation in olfactory epithelia. In this study, we asked if CYP altered globose and horizontal basal cell proliferation in the murine main olfactory epithelium (MOE) and vomeronasal organ (VNO). We used antibodies for Ki67, a marker strictly associated with cell proliferation, and Keratin 5, a marker for the cytoskeleton of horizontal basal cells. Our results revealed a significant CYP-induced decrease in the number of proliferative cells in both epithelia, especially globose basal cells in the MOE, within the first 1–2 days postinjection. Recovery of cell renewal was apparent 6 days after injection. The immunohistochemical markers showed significantly higher levels of globose and horizontal basal cell proliferation in CYP-injected mice at 14 and 30 days postinjection compared with control mice. The prolonged proliferative activation of globose and horizontal basal cells suggests that, besides altering proliferation of olfactory epithelia, the epithelial substrate needed for successful cell renewal may be adversely affected by CYP.