bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel long noncoding RNA, LOC440173, promotes the progression of esophageal squamous cell carcinoma by modulating the miR‐30d‐5p/HDAC9 axis and the epithelial–mesenchymal transition
Authors: Wang Gaoyan , Feng Bo , Niu Yunfeng , Wu Jianhua , Yang Yang , Shen Supeng , Guo Yanli , Liang Jia , Guo Wei , Dong Zhiming 
Published: October 2020

AbstractCountless evidence suggests that long noncoding RNAs (lncRNAs) are involved in human malignant cancers, including esophageal squamous cell carcinoma (ESCC), although their exact function remains unclear. In the present study, we aimed to investigate the roles and molecular mechanisms of the lncRNA LOC440173 in ESCC progression. Microarray analysis and quantitative real‐time polymerase chain reaction were conducted to measure the expression levels of LOC440173 and miR‐30d‐5p. The biological function of this lncRNA was investigated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium, clone formation, and transwell assays, as well as flow cytometry and Western blot analysis. The function of LOC440173 was validated in vivo using tumor xenografts. The regulatory network of LOC440173/miR‐30d‐5p/HDAC9 was established using bioinformatic analysis and verified with dual‐luciferase reporter assays, RNA immunoprecipitation assay, and rescue experiments. The expression level of LOC440173 was significantly increased in ESCC tissues and esophageal carcinoma cells. High LOC440173 expression was correlated with histological grade, tumor invasion depth, lymph node metastasis, and TNM stage. Overexpression of LOC440173 promoted esophageal cancer cell proliferation, migration, and invasion, as well as the epithelial–mesenchymal transition (EMT) process in vitro, and facilitated tumor growth in vivo. MicroRNA‐30d‐5p (miR‐30d‐5p) was downregulated in ESCC tissues and acted as a direct binding target of LOC440173 during the regulation of HDAC9 expression in esophageal carcinoma cells. In conclusion, LOC440173 exerts a promotive role in ESCC tumorigenesis by targeting the miR‐30d‐5p/HDAC9 axis and regulating the EMT process. LOC440173 might be a new therapeutic target for the treatment of ESCC.
Plasma Neurofilament Light as a Biomarker of Neurological Involvement in Wilson's Disease
Authors: Shribman Samuel , Heller Carolin , Burrows Maggie , Heslegrave Amanda , Swift Imogen , Foiani Martha S. , Gillett Godfrey T. , Tsochatzis Emmanuel A. , Rowe James B. , Gerhard Alex , Butler Chris R. , Masellis Mario , Bremner Fion , Martin Alison , Jung Lynne , Cook Paul , Zetterberg Henrik , Bandmann Oliver , Rohrer Jonathan D. , Warner Thomas T. 
Published: October 2020

AbstractBackgroundOutcomes are unpredictable for neurological presentations of Wilson's disease (WD). Dosing regimens for chelation therapy vary and monitoring depends on copper indices, which do not reflect end‐organ damage.ObjectiveTo identify a biomarker for neurological involvement in WD.MethodsNeuronal and glial‐specific proteins were measured in plasma samples from 40 patients and 38 age‐matched controls. Patients were divided into neurological or hepatic presentations and those with recent neurological presentations or deterioration associated with non‐adherence were subcategorized as having active neurological disease. Unified WD Rating Scale scores and copper indices were recorded.ResultsUnlike copper indices, neurofilament light (NfL) concentrations were higher in neurological than hepatic presentations. They were also higher in those with active neurological disease when controlling for severity and correlated with neurological examination subscores in stable patients.ConclusionNfL is a biomarker of neurological involvement with potential use in guiding chelation therapy and clinical trials for novel treatments. © 2020 University College London. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
The Beneficial Effects of Apical Sodium‐Dependent Bile Acid Transporter Inactivation Depend on Dietary Fat Composition
Authors: van de Peppel Ivo P. , Rao Anuradha , Dommerholt Marleen B. , Bongiovanni Laura , Thomas Rachel , de Bruin Alain , Karpen Saul J. , Dawson Paul A. , Verkade Henkjan J. , Jonker Johan W. 
Published: October 2020

ScopeThe apical sodium‐dependent bile acid transporter (ASBT, SLC10A2) is important in the enterohepatic cycling of bile acids and thereby in the intestinal absorption of lipids. ASBT inhibition has been shown to improve aspects of the metabolic syndrome, but the underlying mechanisms have remained unclear. Here, the effect of ASBT inhibition on the uptake of specific fatty acids and its consequences for diet‐induced obesity and non‐alcoholic fatty liver disease (NAFLD) are investigated.MethodsIntestinal fat absorption is determined in mice receiving an ASBT inhibitor and in Asbt−/− mice. Metabolic disease development is determined in Asbt−/− mice receiving a low‐fat control diet (LFD) or high‐fat diet (HFD) rich in saturated fatty acids (SFAs) or PUFAs.ResultsBoth ASBT inhibition and Asbt gene inactivation reduce total fat absorption, particularly of SFAs. Asbt gene inactivation lowers bodyweight gain, improves insulin sensitivity, and decreases the NAFLD activity score upon feeding a HFD rich in SFAs, but not in PUFAs.ConclusionsThe beneficial metabolic effects of ASBT inactivation on diet‐induced obesity depend on decreased intestinal absorption of SFAs, and thus on the dietary fatty acid composition. These findings highlight the importance of dietary fatty acid composition in the therapeutic effects of ASBT inhibition.
Generating anthropomorphic phantoms using fully unsupervised deformable image registration with convolutional neural networks
Authors: Chen Junyu , Li Ye , Du Yong , Frey Eric C. 
Published: October 2020

PurposeComputerized phantoms have been widely used in nuclear medicine imaging for imaging system optimization and validation. Although the existing computerized phantoms can model anatomical variations through organ and phantom scaling, they do not provide a way to fully reproduce the anatomical variations and details seen in humans. In this work, we present a novel registration‐based method for creating highly anatomically detailed computerized phantoms. We experimentally show substantially improved image similarity of the generated phantom to a patient image.MethodsWe propose a deep‐learning‐based unsupervised registration method to generate a highly anatomically detailed computerized phantom by warping an XCAT phantom to a patient computed tomography (CT) scan. We implemented and evaluated the proposed method using the NURBS‐based XCAT phantom and a publicly available low‐dose CT dataset from TCIA. A rigorous tradeoff analysis between image similarity and deformation regularization was conducted to select the loss function and regularization term for the proposed method. A novel SSIM‐based unsupervised objective function was proposed. Finally, ablation studies were conducted to evaluate the performance of the proposed method (using the optimal regularization and loss function) and the current state‐of‐the‐art unsupervised registration methods.ResultsThe proposed method outperformed the state‐of‐the‐art registration methods, such as SyN and VoxelMorph, by more than 8%, measured by the SSIM and less than 30%, by the MSE. The phantom generated by the proposed method was highly detailed and was almost identical in appearance to a patient image.ConclusionsA deep‐learning‐based unsupervised registration method was developed to create anthropomorphic phantoms with anatomies labels that can be used as the basis for modeling organ properties. Experimental results demonstrate the effectiveness of the proposed method. The resulting anthropomorphic phantom is highly realistic. Combined with realistic simulations of the image formation process, the generated phantoms could serve in many applications of medical imaging research.
Characterization of symptom severity and impact on four fecal incontinence phenotypes in women presenting for evaluation
Authors: Hoke Tanya P. , Meyer Isuzu , Blanchard Christina T. , Szychowski Jeff M. , Richter Holly E. 
Published: October 2020

AbstractAimTo characterize symptom‐specific distress and impact on quality of life (QOL) among women with urge, passive, and combined urge/passive fecal incontinence (FI) phenotypes. A secondary aim was to characterize FI symptom‐specific distress and impact on women with a novel fourth phenotype, stress FI.MethodsWomen with at least monthly FI from 2003 to 2017 were included. Participants completed the Modified Manchester Health Questionnaire (MMHQ) including MHQ and Fecal Incontinence Severity Index (FISI). Anorectal manometry (ARM) and endoanal ultrasound (EAUS) testing was performed. Total MHQ and FISI scores were compared across FI subtypes controlling for pertinent baseline covariates.ResultsThe cohort included 404 subjects, 220 meeting criteria for urge FI, 67 passive FI, and 117 combined urge/passive FI. On MHQ, women with combined urge/passive FI were most impacted (p < 0.01). FISI scores were significantly different from combined urge/passive FI having the greatest impact (38.1 ± 12.5) and urge FI (31.1 ± 11.3), p < 0.01 having the least. No differences were observed in ARM measurements or anal sphincter defects among the three groups (all p > 0.05). Twenty‐nine subjects were identified with stress FI. There were no differences in overall MHQ or FISI scores or anal sphincter evaluation among the urge, passive, and stress FI groups (all p > 0.05).ConclusionWomen with combined urge/passive FI have higher symptom distress and impact on QOL than urge or passive FI alone. Further research is needed to determine the significance of stress FI as a subtype and response to treatment.
Effects on body weight, eating behavior, and quality of life of a low‐energy diet combined with behavioral group treatment of persons with class II or III obesity: A 2‐year pilot study
Authors: Karlsson Jan , Galavazi Marije , Jansson Stefan , Jendle Johan 
Published: October 2020

SummaryObjectiveObesity is associated with reduced health‐related quality of life (HRQoL). Outcomes of nonsurgical weight loss treatment on HRQoL are inconsistent and it is unclear how much weight reduction, or what type of treatment, is required for significant improvements. This study aimed to evaluate the effects of a lifestyle intervention program on weight, eating behaviors, and HRQoL, and to describe participants' experiences of treatment.MethodsThis 2‐year intervention trial in persons with class II or III obesity comprised a 3‐month liquid low‐energy diet (880 kcal/d) followed by a 3‐month reintroduction to regular foods, combined with behavioral group treatment.ResultsFifty‐five participants (73% women) were included, mean (SD) age 43.2 (12.4) years, and mean body mass index 42.0 (6.0) kg/m2. Mean weight loss at 6, 12, and 24 months was 18.9%, 13.7%, and 7.2%, respectively. Short‐ and long‐term effects on eating behavior were favorable. Twelve of 14 HRQoL domains were improved at 6 months, compared to eight domains at 12 months. After 24 months, 2 of 14 domains, physical and psychosocial functioning, were improved. The treatment program was well accepted by the participants.ConclusionsSubstantial weight loss after 6 months was associated with extensive improvements in HRQoL, comprising the physical, psychosocial, and mental domains. Significant weight regain was observed between 6 and 24 months follow‐up. Modest weight loss after 24 months was associated with moderate improvement in physical functioning and large improvement in psychosocial functioning. The effect on psychosocial functioning is most likely related to both weight loss and behavioral treatment.
Long‐term effect of first‐line injectable multiple sclerosis treatments: Input of a time‐dependent propensity score
Authors: Lefort Mathilde , Foucher Yohann , Lenain Remi , Vukusic Sandra , Edan Gilles , Leray Emmanuelle 
Published: October 2020

AbstractPurposeThe long‐term effect of beta‐interferon and glatiramer acetate on multiple sclerosis (MS) disability progression has resulted in controversial results, probably due to a lack of appropriate control of biases as raised in observational studies. In particular, the time of the therapeutic decision is difficult to define when the controls are not treated.MethodsThis retrospective observational study was based on a series of patients from the MS expert center in Rennes, France. We used a time‐dependent propensity score defined as the linear predictor of a Cox model estimating the hazard of being treated at each time from MS onset. The matching procedure resulted in two groups: patients matched as treated and as not yet treated. The restricted mean times (RMST) to reach a moderate level of disability or worsening of the disability were compared between the two groups in an intention‐to‐treat analysis.ResultsOf the 2383 patients included in the study, 556 were matched as treated. The matching procedure provided a good balance of both the time‐fixed and the time‐dependent covariates. A slight difference was observed for the time to reach a moderate level of disability, in favor of the “not yet treated” group (difference in the RMST: −0.62 [−0.91; −0.33]) while no difference was found in terms of worsening of the disability (−0.03 [−0.24; 0.33]).ConclusionThis unexpected result is probably due to unmeasured confounders. However, this time‐dependent PS warrants consideration in long‐term effectiveness studies.
Prescription Medication Use in Older Adults Without Major Cardiovascular Disease Enrolled in the Aspirin in Reducing Events in the Elderly (ASPREE) Clinical Trial
Authors: Lockery Jessica E. , Ernst Michael E. , Broder Jonathan C. , Orchard Suzanne G. , Murray Anne , Nelson Mark R. , Stocks Nigel P. , Wolfe Rory , Reid Christopher M. , Liew Danny , Woods Robyn L. ,   the ASPREE Investigator Group
Published: October 2020

Background
Efforts to minimize medication risks among older adults include avoidance of potentially inappropriate medications. Contemporary analysis of medication use in community‐dwelling older people compared with the general population is lacking.
Participants
A total of 19,114 community‐dwelling adults in Australia and the United States aged 70 years or older (65 years or older for U.S. minorities) without histories of major cardiovascular disease, cognitive impairment, or disability participated in a randomized, placebo‐controlled trial of aspirin: ASPirin in Reducing Events in the Elderly study.
Measurements
Prescribed baseline medications obtained by self‐report and medical record review were grouped by World Health Organization Anatomic and Therapeutic Chemical category. Potentially inappropriate medications were defined using a modified American Geriatrics Society Beers Criteria. Polypharmacy was defined as 5 or more medications, and hyperpolypharmacy defined as 10 or more medications. Cross‐sectional descriptive statistics and adjusted odds ratios were computed.
Results
The median number of prescription medications per participant was three, regardless of age. Women had a higher medication prevalence. Cardiovascular drugs (primarily antihypertensives) were the most commonly reported (64%). Overall, 39% of the cohort reported taking at least one potentially inappropriate medication, with proton‐pump inhibitors being the most commonly reported (21.2% of cohort). Of the cohort, 27% had polypharmacy, and 2% hyperpolypharmacy. Age 75 years or older, less than 12 years of education, hypertension, diabetes mellitus, chronic kidney disease, frailty, gastrointestinal complaint, and depressive symptoms were associated with an increased likelihood of potentially inappropriate medications and polypharmacy. For almost all medication classes, prevalence was equivalent or lower than the general older population.
Conclusion
Overall medication burden and polypharmacy are low in older adults free of major cardiovascular disease, disability, and cognitive impairment. The prevalence of potentially inappropriate medications is higher than previously reported and similar to more vulnerable populations as a result of the introduction of proton‐pump inhibitors to the American Geriatrics Society Beers Criteria. Longitudinal follow‐up is required to further understand the balance of benefits and risks for potentially inappropriate medications and polypharmacy in community‐dwelling older people.
Drug‐Induced Ototoxicity: A Comprehensive Review and Reference Guide
Authors: Rizk, Habib G. , Lee, Joshua A. , Liu, Yuan F. , Endriukaitis, Lauren , Isaac, Julianne L. , Bullington Wendy M. 
Published: October 2020

ObjectiveIn an era of increasing polypharmacy, adverse drug effects such as ototoxicity have significant public health implications. Despite the availability of evidence, many health care professionals may not know the risk of ototoxicity in common medications. Therefore, the aim of this review is to provide a comprehensive, easy to use, ototoxic profile of medications with an assessment of supporting evidence.MethodsMedications of interest were identified through adverse drug reaction reports derived from Micromedex (IBM), Lexicomp (Wolters Kluwer), and the textbook,Drug Induced Diseases: Prevention, Detection, and Management. Additional evidence was identified though a query of PubMed and the Cochrane database. Evidence of causality was graded according to the following: A (randomized, controlled clinical trials), B (nonrandomized clinical trials, prospective observational studies, cohort studies, retrospective studies, case‐controlled studies, and/or postmarketing surveillance studies), and C (case reports/case series).ResultsA total of 194 systemically administered medications associated with ototoxicity were identified, most commonly antimicrobials (53), psychotropics (21), antihypertensive/antiarrhythmics (19), nonsteroidal antiinflammatory drugs (18), and antineoplastics (16). There was evidence of cochleotoxicity in 165 medications (evidence grading A [22], B [77], C [69]), vestibulotoxicity in 100 medications (evidence grading A [23], B [47], and C [30]), and dizziness in 142 medications (evidence grading A [50], B [76], and C [16]). In addition, a review of the evidence of ototoxicity in ototopical medications is also reviewed.ConclusionThe effect and severity of ototoxicity can vary immensely depending on pharmacological and individual patient risk factors. The intent of this comprehensive review was to help health care providers of all sectors obtain a deeper knowledge of drug‐induced ototoxicity to make more informed management decisions for their patients.
Antimicrobial films containing hybrid systems aiming at packaging applications
Authors: Camani Paulo H , da Silva Torin Rondes F , de Souza Clóvis WO , Zanata Leonardo , dos Santos Rosa Derval 
Published: October 2020

AbstractA critical issue in active packaging development using essential oils (EOs) is the high concentrations of these to obtain antimicrobial activity in the films. Therefore, this work was carried out to develop nanocomposite films, pursuing a potential minimal EO concentration with antimicrobial effectiveness, which could be applied in packaging. The films were prepared using low‐density polyethylene (LDPE) containing a hybrid of montmorillonite and essential oil (MMT‐EO), using two different EOs, carvacrol and eugenol, with 2 and 6 wt% oil concentration. The films were obtained in three steps. In the first (hybrid production), mixtures of montmorillonite clay with eugenol or carvacrol EOs were prepared. In the second (hybrid incorporation), these hybrids were incorporated into LDPE, obtaining LDPE/MMT‐EO nanocomposites. Finally, a thermoforming process prepared the polymeric films. The samples were characterized by XRD and mechanical, contact angle and antimicrobial properties. The XRD results showed higher crystallinity for LDPE/MMT‐EO compared to LDPE. The MMT was exfoliated into lamella forms, which could work as a physical barrier, reducing the oil diffusion. Besides, the contact angle results showed an increase in the hydrophilicity with the addition of the hybrids, which improved the antimicrobial action of the film. LDPE/MMT‐E3 (1 wt% MMT and 2 wt% eugenol) showed the highest crystallinity, oil diffusivity, and mechanical and antimicrobial properties. These samples presented a reduction of a 2 log count of Staphylococcus aureus. The sum of the structural and antimicrobial properties of the LDPE/MMT‐E3 film indicates its potential for food packaging. © 2020 Society of Industrial Chemistry
InsecticidalRNAinterference, thinking beyond longdsRNA
Authors: Flynt Alex S 
Published: October 2020

AbstractOver 20 years ago double‐stranded RNA (dsRNA) was described as the trigger of RNAi interference (RNAi)‐based gene silencing. This paradigm has held since, especially for insect biopesticide technologies where dsRNAs, similar to those described in 1998, are used to inhibit gene expression. In the intervening years, investigation of RNAi pathways has revealed the small RNA effectors of RNAi are diverse and rapidly evolving. The rich biology of insect small RNAs suggests potential to use multiple RNAi modes for manipulating gene expression. By exploiting different RNAi pathways, the menu of options for pest control can be expanded and could lead to better tailored solutions. Fortunately, basic delivery strategies used for dsRNA such as direct application or transgenic expression will translate well between RNAs transiting different RNAi pathways. Importantly, further engineering of RNAi‐based biopesticides may provide an opportunity to address dsRNA insensitivity seen in some pests. Characterization of RNAi pathways unique to target species will be indispensable to this end and may require thinking beyond long dsRNA. © 2020 Society of Chemical Industry
Why people like or dislike large wood in rivers—a representative survey of the general public in Germany
Authors: Gapinski Cedric Mats , Hermes Johannes , von Haaren Christina 
Published: October 2020

AbstractFor the restoration of medium and small rivers, the reintroduction of large wood (LW) is crucial. Despite the wide communication of the ecological key functions of LW, residents rejected its reintroduction in a restoration project at the river Mulde (Dessau‐Roßlau, Germany). To determine whether this is a local or widespread phenomenon in Germany, we investigated (a) the German population's attitude toward LW, (b) preferred quantities of LW introduction, and (c) the effects of flood experiences and other sociodemographic characteristics on these preferences. We conducted a nationwide and representative online survey (n = 2,100), including rating‐scale statements and a choice experiment (CE). Regarding the rating statements, we found that a majority of respondents (57–67%) is convinced of the advantages of LW reintroduction. However, 47–60% considered LW to be dangerous for canoeists or during floods. For the CE (n = 743), we defined an LW attribute and added information on possible effects. Conditional logit models showed a strong preference for the highest amount of LW, with an odds ratio 5.47 times higher than for the status quo without LW. We also found that personal flood experiences reduce the preferred LW quantities. In contrast, females, higher educational levels, the youngest and oldest age groups, and especially frequent river visitors preferred higher LW amounts. Since the commitment of young people to environmental issues is currently increasing, we believe that specific environmental education opportunities for this group located along the river can contribute significantly to increase acceptance.