bluuebunny/crossref_metadata_2025_split huggingface dataset:
PROMISCUOUS 2.0: a resource for drug-repositioning
Authors: Gallo Kathleen , Goede Andrean , Eckert Andreas , Moahamed Barbara , Preissner Robert , Gohlke Björn-Oliver 
Published: October 2020

Abstract
The development of new drugs for diseases is a time-consuming, costly and risky process. In recent years, many drugs could be approved for other indications. This repurposing process allows to effectively reduce development costs, time and, ultimately, save patients’ lives. During the ongoing COVID-19 pandemic, drug repositioning has gained widespread attention as a fast opportunity to find potential treatments against the newly emerging disease. In order to expand this field to researchers with varying levels of experience, we made an effort to open it to all users (meaning novices as well as experts in cheminformatics) by significantly improving the entry-level user experience. The browsing functionality can be used as a global entry point to collect further information with regards to small molecules (∼1 million), side-effects (∼110 000) or drug-target interactions (∼3 million). The drug-repositioning tab for small molecules will also suggest possible drug-repositioning opportunities to the user by using structural similarity measurements for small molecules using two different approaches. Additionally, using information from the Promiscuous 2.0 Database, lists of candidate drugs for given indications were precomputed, including a section dedicated to potential treatments for COVID-19. All the information is interconnected by a dynamic network-based visualization to identify new indications for available compounds. Promiscuous 2.0 is unique in its functionality and is publicly available at http://bioinformatics.charite.de/promiscuous2.
MarkerDB: an online database of molecular biomarkers
Authors: Wishart David S , Bartok Brendan , Oler Eponine , Liang Kevin Y H , Budinski Zachary , Berjanskii Mark , Guo AnChi , Cao Xuan , Wilson Michael 
Published: October 2020

Abstract
MarkerDB is a freely available electronic database that attempts to consolidate information on all known clinical and a selected set of pre-clinical molecular biomarkers into a single resource. The database includes four major types of molecular biomarkers (chemical, protein, DNA [genetic] and karyotypic) and four biomarker categories (diagnostic, predictive, prognostic and exposure). MarkerDB provides information such as: biomarker names and synonyms, associated conditions or pathologies, detailed disease descriptions, detailed biomarker descriptions, biomarker specificity, sensitivity and ROC curves, standard reference values (for protein and chemical markers), variants (for SNP or genetic markers), sequence information (for genetic and protein markers), molecular structures (for protein and chemical markers), tissue or biofluid sources (for protein and chemical markers), chromosomal location and structure (for genetic and karyotype markers), clinical approval status and relevant literature references. Users can browse the data by conditions, condition categories, biomarker types, biomarker categories or search by sequence similarity through the advanced search function. Currently, the database contains 142 protein biomarkers, 1089 chemical biomarkers, 154 karyotype biomarkers and 26 374 genetic markers. These are categorized into 25 560 diagnostic biomarkers, 102 prognostic biomarkers, 265 exposure biomarkers and 6746 predictive biomarkers or biomarker panels. Collectively, these markers can be used to detect, monitor or predict 670 specific human conditions which are grouped into 27 broad condition categories. MarkerDB is available at https://markerdb.ca.
Adult precision medicine: learning from the past to enhance the future
Authors: Ghiaseddin Ashley , Hoang Minh Lan B , Janiszewska Michalina , Shin David , Wick Wolfgang , Mitchell Duane A , Wen Patrick Y , Grossman Stuart A 
Published: October 2020

AbstractDespite therapeutic advances for other malignancies, gliomas remain challenging solid tumors to treat. Complete surgical resection is nearly impossible due to gliomas’ diffuse infiltrative nature, and treatment is hampered by restricted access to the tumors due to limited transport across the blood–brain barrier. Recent advances in genomic studies and next-generation sequencing techniques have led to a better understanding of gliomas and identification of potential aberrant signaling pathways. Targeting the specific genomic abnormalities via novel molecular therapies has opened a new avenue in the management of gliomas, with encouraging results in preclinical studies and early clinical trials. However, molecular characterization of gliomas revealed significant heterogeneity, which poses a challenge for targeted therapeutic approaches. In this context, leading neuro-oncology researchers and clinicians, industry innovators, and patient advocates convened at the inaugural annual Remission Summit held in Orlando, FL in February 2019 to discuss the latest advances in immunotherapy and precision medicine approaches for the treatment of adult and pediatric brain tumors and outline the unanswered questions, challenges, and opportunities that lay ahead for advancing the duration and quality of life for patients with brain tumors. Here, we provide historical context for precision medicine in other cancers, present emerging approaches for gliomas, discuss their limitations, and outline the steps necessary for future success. We focus on the advances in small molecule targeted therapy, as the use of immunotherapy as an emerging precision medicine modality for glioma treatment has recently been reviewed by our colleagues.
Content appealing to youth and spend characteristics of electronic cigarette video advertisements
Authors: Hoetger Cosima , Wall Catherine S J , Rudy Alyssa K , Nicksic Nicole E , Bhatt Sohum M , Sey Nancy Y A , Khan Mishaal , Braxton Destini , Barnes Andrew J , Cobb Caroline O 
Published: October 2020

Abstract

Background
The US electronic cigarette (ECIG) market and use behavior continues to rise, warranting investigation of ECIG advertisement (ad) content within media channels frequented by youth including internet and television (TV). In order to inform potential policy regulations, this content analysis sought to assess the prevalence of youth-appealing content and spend characteristics among ECIG video ads.

Methods
Between 2015 and 2016, 46 ECIG video ads were identified using an ad-tracking firm and were coded using the Content Appealing to Youth (CAY) index. Bivariate analyses and analysis of variance were used to compare CAY indices between online and TV ads and by ECIG brands. Ad-specific spend and source information, including website/TV program targeted were examined descriptively.

Results
Common youth-appealing features included use of animation (56.5%) and content related to positive sensations (52.2%), promoting mood (34.8%), individuality/freedom (23.9%) and addiction (19.6%). Features not associated with youth appeal also were prevalent. Few differences were observed by media source or ECIG brand. TV ads accounted for the largest spend, and Vuse was the top spending brand. Websites/TV programs were diverse.

Conclusions
Findings support regulatory efforts to restrict the use of youth-appealing content within ECIG ads as well as the reduction of media sources available for ECIG marketing.
The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms
Authors: Cai Guoqi , Aitken Dawn , Laslett Laura L , Hill Catherine , Wluka Anita E , March Lyn , Cicuttini Flavia , Pelletier Jean-Pierre , Martel-Pelletier Johanne , Jones Graeme 
Published: October 2020

Abstract

Objective
To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA.

Methods
In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months.

Results
Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: −53.0mm3, 95% CI: −100.0, −6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: −8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals.

Conclusions
In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms.
Immunoglobulin G of systemic sclerosis patients programs a pro-inflammatory and profibrotic phenotype in monocyte-like THP-1 cells
Authors: Murthy Sripriya , Wannick Melanie , Eleftheriadis Georgios , Müller Antje , Luo Jiao , Busch Hauke , Dalmann Anja , Riemekasten Gabriela , Sadik Christian D 
Published: October 2020

Abstract

Objectives
Functional IgG autoantibodies against diverse G protein-coupled receptors, i.e. antibodies with agonistic or antagonistic activity at these receptors, are abundant in human serum. Their levels are altered in patients with SSc, and autoantibodies against angiotensin II receptor 1 (ATR1) and endothelin receptor A (ETA) have been suggested to drive SSc by inducing the chemokines CXCL8 and CCL18 in the blood. The objective of our study is to profile the effect of IgG in SSc (SSc-IgG) on the production of soluble mediators in monocytic cells.

Methods
Monocyte-like THP-1 cells were stimulated with SSc-IgG and their secretome was analysed. Furthermore, the significance of major pro-inflammatory pathways for the induction of CXCL8 and CCL18 in response to SSc-IgG was assessed by a pharmacological approach.

Results
Stimulation with SSc-IgG significantly alters the secretome of THP-1 cells towards a general pro-inflammatory and profibrotic phenotype, which includes an increase of CCL18 and CXCL8. The consequent expression profiles vary depending on the individual donor of the SSc-IgG. CCL18 and CXCL8 expression is thus regulated differentially, with AP-1 driving the induction of both CCL18 and CXCL8 and the TAK/IKK-β/NF-κB pathway and ERK1/2 driving that of CXCL8.

Conclusions
Our results suggest that SSc-IgG contributes to the generation of the pro-inflammatory/profibrotic tissue milieu characteristic of SSc by its induction of a respective phenotype in monocytes. Furthermore, our results highlight AP-1 as a critical regulator of gene transcription of CCL18 in monocytic cells and as a promising pharmacological therapeutic target for the treatment of SSc.
Associations between parent-reported and objectively measured sleep duration and timing in infants at age 6 months
Authors: Quante Mirja , Hong Benjamin , von Ash Tayla , Yu Xinting , Kaplan Emily R , Rueschman Michael , Jackson Chandra L , Haneuse Sebastien , Davison Kirsten , Taveras Elsie M , Redline Susan 
Published: October 2020

AbstractStudy ObjectivesTo compare the estimates of sleep duration and timing from survey, diary, and actigraphy in infants at age 6 months, overall and by select demographics and other factors.MethodsIn total, 314 infants participating in the Rise & SHINE (Sleep Health in Infancy & Early Childhood study) cohort in Boston, MA, USA, wore an actigraph on their left ankle for 7 days. Parents concurrently completed a sleep diary and the expanded version of the Brief Infant Sleep Questionnaire. Concordance between parent-reported and objective sleep estimates was assessed using Bland–Altman plots, Spearman’s rank correlations, intraclass correlations, and linear regression models.ResultsMean infant age was 6.4 (0.6 SD) months; 51% were female and 42% were Non-Hispanic white. Mean total sleep duration using actigraphy was 526 (67 SD) minutes per night, 143 (42 SD) minutes per day, and 460 (100 SD) minutes during the longest nighttime sleep period. Relative to actigraphy, parent-completed survey and diary overestimated total day (by 29 and 31 minutes, respectively) and night sleep duration (67 and 43 minutes, respectively) and underestimated the longest sleep (58 minutes), with the highest agreement for sleep onset and offset timing (differences &lt; 30 minutes). There was a tendency toward greater bias among short- and long-sleeping infants. Self-reporting bias for diary-measured longest nighttime sleep and total night sleep duration was higher in infants of parents reporting a problem with their baby’s night awakenings and in low-income families, respectively.ConclusionsOur findings underscore the need to be cautious when comparing findings across studies using different sleep assessment methods.
Comparison of single-channel EEG, actigraphy, and sleep diary in cognitively normal and mildly impaired older adults
Authors: Chou Chris A , Toedebusch Cristina D , Redrick Tiara , Freund David , McLeland Jennifer S , Morris John C , Holtzman David M , Lucey Brendan P 
Published: October 2020

AbstractStudy ObjectivesMultiple methods for monitoring sleep-wake activity have identified sleep disturbances as risk factors for Alzheimer disease (AD). In order to identify the level of agreement between different methods, we compared sleep parameters derived from single-channel EEG (scEEG), actigraphy, and sleep diaries in cognitively normal and mildly impaired older adults.MethodsTwo hundred ninety-three participants were monitored at home for up to six nights with scEEG, actigraphy, and sleep diaries. Total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) were calculated using each of these methods. In 109 of the 293 participants, the ratio of cerebrospinal fluid concentrations of phosphorylated tau (p-tau) and amyloid-β-42 (Aβ42) was used as a biomarker for AD pathology.ResultsAgreement was highest for TST across instruments, especially in cognitively normal older adults. Overall, scEEG and actigraphy appeared to have greater agreement for multiple sleep parameters than for scEEG and diary or actigraphy and diary. Levels of agreement between scEEG and actigraphy overall decreased in mildly impaired participants and those with biomarker evidence of AD pathology, especially for measurements of TST.ConclusionsCaution should be exercised when comparing scEEG and actigraphy in individuals with mild cognitive impairment or with AD pathology. Sleep diaries may capture different aspects of sleep compared to scEEG and actigraphy. Additional studies comparing different methods of measuring sleep-wake activity in older adults are necessary to allow for comparison between studies using different methods.
sORF-Encoded Polypeptide SEP1 Is a Novel Virulence Factor of Phytophthora Pathogens
Authors: Wang Nan , Yin Zhiyuan , Duan Weiwei , Zhang Xiong , Pi Lei , Zhang Yifan , Dou Daolong 
Published: October 2020

Diseases caused by the notorious Phytophthora spp. result in enormous economic losses to crops and forests. Increasing evidence suggests that small open reading frame-encoded polypeptides (SEPs) participate in environmental responses of animals, plants, and fungi. However, it remains largely unknown whether Phytophthora pathogens produce SEPs. Here, we systematically predicted and identified 96 SEP candidates in P. capsici. Among them, three may induce stable cell death in Nicotiana benthamiana. Phytophthora-specific and conserved SEP1 facilitated P. capsici infection. PcSEP1-induced cell death is BAK1 and SOBIR1 independent and is correlated with its virulence function. Finally, PcSEP1 may be targeted to the apoplast for carrying out its functions, for which the C terminus is indispensable. Together, our results demonstrated that SEP1 is a new virulence factor, and previously unknown SEPs may act as effector proteins in Phytophthora pathogens. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Adverse respiratory events with sevoflurane compared with desflurane in ambulatory surgery
Authors: Chen Wei-Shan , Chiang Min-Hsien , Hung Kuo-Chuan , Lin Kai-Lieh , Wang Chih-Hsien , Poon Yan-Yuen , Luo Sheng-Dean , Wu Shao-Chun 
Published: October 2020

BACKGROUND
An increasing number of studies have concluded that the number of adverse events in the upper airway caused by desflurane does not differ significantly from the number of adverse events caused by sevoflurane. The advantages of desflurane in ambulatory surgery should be reassessed.

OBJECTIVES
The aim of this study was to compare adverse respiratory events and recovery outcomes in patients undergoing desflurane or sevoflurane-based anaesthesia in ambulatory surgery.

DESIGN
A systematic review and meta-analysis of randomised controlled trials (RCTs).

DATA SOURCES
A systematic search for eligible RCTs in PubMed, Medline, Cochrane Central Register of Controlled Trials, ScienceDirect and Embase published up to June 2019.

ELIGIBILITY CRITERIA
RCTs investigating the occurrence of adverse respiratory events, including airway irritation, stridor, coughing, respiratory distress and laryngospasm, emergence agitation, postoperative nausea and vomiting (PONV), time to eye opening and time to discharge from the operation room after desflurane or sevoflurane-based anaesthesia.

RESULTS
Thirteen trials were included and analysed. A total of 634 patients were included in the desflurane group, and 633 patients in the sevoflurane group. The occurrence of respiratory complications was significantly higher with desflurane-based anaesthesia than with sevoflurane-based anaesthesia (Total n = 673, 20.0 vs. 12.8%, relative risk (RR) 1.59 (95% CI 1.15 to 2.20)) with low heterogeneity (I
2 = 20%). There was no difference in the occurrence of emergence agitation (Total n = 626, 29.1 vs. 27.2%, RR 1.05 (95% CI 0.84 to 1.30)) or the incidence of PONV between the desflurane and sevoflurane groups (Total n = 989, 19.0 vs. 21.0%, RR 0.95 (95% CI 0.71 to 1.26)). Time to eye opening was significantly faster with desflurane than that with sevoflurane (Total n = 1072, mean difference = −3.32 min (95% CI −4.02 to −2.61)) with a substantial heterogeneity (I
2 = 72.6%). There was no significant difference in the time to discharge from the operation room between the two groups (Total n = 1056, mean difference = −0.45 min (95% CI −5.89 to 4.99)).

CONCLUSION
Despite recent reports that there is no significant difference in adverse respiratory events between desflurane and sevoflurane, a pooled analysis revealed that desflurane resulted in a higher rate than sevoflurane. Therefore, the consequences of desflurane should not be neglected and its airway irritant properties should be taken into account.

TRIAL REGISTRATION
PROSPERO (CRD42019147939).
Inhibition of miR-188-5p Suppresses Progression of Experimental Abdominal Aortic Aneurysms
Authors: Huang Tingting , Liu Shuai , Liu Rui , Pan Baihong , Wang Wei 
Published: October 2020

Abstract:
Abdominal aortic aneurysm (AAA) is an aging-related degenerative disease. miR-188-5p was reported to induce cell senescence and play a key role in aging-related disease. Therefore, in this study, we investigated miR-188-5p expression during progression in experimental AAAs. Furthermore, we investigated whether inhibition of miR-188-5p could suppress AAA progression. Experimental AAAs were created in 9–12-week-old male C57BL/6J mice by transient intra-aortic infusion of porcine pancreatic elastase. Expression of miR-188-5p levels were assessed in aneurysmal and control aortae during the progression of aneurysm. For inhibition experiment, miR-188 inhibiting group mice were injected with AAV2-miR188-5p sponge through tail vein and control group mice were injected with AAV2-CMV-GFP. Influences on experimental AAA progression were assessed by measurements of aortic diameter and histopathologic analysis at sacrifice. Meanwhile, immunohistochemistry and fluorescence in situ hybridization were used to determine the inflammatory cells infiltration and colocalization of miR-188-5p in aortic sections. Expression of miR-188-5p is upregulated during progression of AAA. Importantly, miR-188-5p inhibition treatment prevented enlargement of experimental aneurysms. Meanwhile, miR-188-5p inhibition regimens attenuated medial elastin degradation, smooth muscle cell depletion, and mural angiogenesis and the accumulation of macrophages, T cells, and angiogenesis. Furthermore, colocalization of miR188-5p with CD68 and CD3 was observed, which suggest miR-188-5p was expressed mainly in infiltrated macrophages and T cells. Expression of miR-188-5p is increased in experimental AAAs. Treatment with miR-188-5p inhibition limits experimental AAA progression, with histologic evidence of reduced neovessels and attenuated mural leukocyte infiltration. These findings underscore the potential significance of miR-188-5p in aneurysm pathogenesis and as a target for suppression of AAA disease.
Three-Year Outcomes of Second-generation Trabecular Micro-bypass Stents (iStent inject) With Phacoemulsification in Various Glaucoma Subtypes and Severities
Authors: Salimi Ali , Watt Harrison , Harasymowycz Paul 
Published: October 2020

Precis:
This longitudinal case series provides valuable long-term data on the safety and efficacy of iStent inject with concomitant cataract surgery. Patients experienced significant and durable reductions in both intraocular pressure (IOP) and medication burden through 3 years postoperative.

Purpose:
The purpose of this study was to examine the 3-year effectiveness and safety of iStent inject second-generation trabecular micro-bypass stent implantation with concomitant phacoemulsification cataract surgery in eyes with various glaucoma subtypes and severities.

Methods:
This was a single-center consecutive case series. Three-year outcomes included mean IOP and medications, the proportions of eyes with IOP ≤18, ≤15, and ≤12 mm Hg, and success (absence of secondary glaucoma interventions). Safety included best-corrected visual acuity (BCVA), cup-to-disc ratio, visual field (VF) mean deviation, retinal nerve fiber layer (RNFL), and ganglion cell-inner plexiform layer (GCIPL) thickness, and adverse events.

Results:
A total of 124 eyes with different glaucoma subtypes and severities were included. At 3 years postoperative, mean IOP reduced from 16.90±3.85 mm Hg preoperatively to 13.17±2.83 mm Hg (22% reduction, P<0.001) and mean medication burden decreased from 2.38±1.29 medications preoperatively to 1.16±1.22 medications (51% reduction, P<0.001). At 3 years, 96% of eyes achieved IOP ≤18 mm Hg (vs. 69% preoperatively), 80% of eyes achieved IOP ≤15 mm Hg (vs. 40% preoperatively), and 42% of eyes achieved IOP ≤12 mm Hg (vs. 7% preoperatively) with 76% of eyes eliminating ≥1 medication and 37% of eyes eliminating ≥2 medications versus preoperative medication burden. The 3-year cumulative survival rate was 74%. Postphacoemulsification BCVA improvement was preserved, and cup-to-disc ratio, VF mean deviation, and RNFL and GCIPL thickness remained stable. A favorable safety profile included no intraoperative complications and few, transient, postoperative adverse events.

Conclusion:
Significant and sustained IOP and medication reductions were achieved through 3 years after iStent inject implantation with cataract surgery in a real-world clinical population with mild-to-severe glaucoma, along with favorable safety including stable BCVA, VF, and RNFL and GCIPL thickness.