bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are there broad absorption-line blazars?
Authors: Mishra Sapna , Krishna Gopal , Chand Hum , Chand Krishan , Ojha Vineet 
Published: August 2019

Abstract
We report the first systematic search for blazars among broad-absorption-line (BAL) quasars. This is based on our intranight optical monitoring of a well-defined sample of 10 candidates selected on the criteria of a flat spectrum and an abnormally high linear polarization at radio wavelengths. A small population of BAL blazars can be expected in the ‘polar model’ of BAL quasars. However, no such case is found, since none of our 30 monitoring sessions devoted to the 10 candidates yielded a positive detection of intra-night optical variability (INOV), which is uncharacteristic of blazars. This lack of INOV detection contrasts with the high duty cycle of INOV observed for a comparison sample of 15 ‘normal’ (i.e., non-BAL) blazars. Some possible implications of this are pointed out.
Highly efficacious antiviral protection of plants by small interfering RNAs identified in vitro
Authors: Gago-Zachert Selma , Schuck Jana , Weinholdt Claus , Knoblich Marie , Pantaleo Vitantonio , Grosse Ivo , Gursinsky Torsten , Behrens Sven-Erik 
Published: August 2019

Abstract
In response to a viral infection, the plant’s RNA silencing machinery processes viral RNAs into a huge number of small interfering RNAs (siRNAs). However, a very few of these siRNAs actually interfere with viral replication. A reliable approach to identify these immunologically effective siRNAs (esiRNAs) and to define the characteristics underlying their activity has not been available so far. Here, we develop a novel screening approach that enables a rapid functional identification of antiviral esiRNAs. Tests on the efficacy of such identified esiRNAs of a model virus achieved a virtual full protection of plants against a massive subsequent infection in transient applications. We find that the functionality of esiRNAs depends crucially on two properties: the binding affinity to Argonaute proteins and the ability to access the target RNA. The ability to rapidly identify functional esiRNAs could be of great benefit for all RNA silencing-based plant protection measures against viruses and other pathogens.
eRF1 mediates codon usage effects on mRNA translation efficiency through premature termination at rare codons
Authors: Yang Qian , Yu Chien-Hung , Zhao Fangzhou , Dang Yunkun , Wu Cheng , Xie Pancheng , Sachs Matthew S , Liu Yi 
Published: August 2019

AbstractCodon usage bias is a universal feature of eukaryotic and prokaryotic genomes and plays an important role in regulating gene expression levels. A major role of codon usage is thought to regulate protein expression levels by affecting mRNA translation efficiency, but the underlying mechanism is unclear. By analyzing ribosome profiling results, here we showed that codon usage regulates translation elongation rate and that rare codons are decoded more slowly than common codons in all codon families in Neurospora. Rare codons resulted in ribosome stalling in manners both dependent and independent of protein sequence context and caused premature translation termination. This mechanism was shown to be conserved in Drosophila cells. In both Neurospora and Drosophila cells, codon usage plays an important role in regulating mRNA translation efficiency. We found that the rare codon-dependent premature termination is mediated by the translation termination factor eRF1, which recognizes ribosomes stalled on rare sense codons. Silencing of eRF1 expression resulted in codon usage-dependent changes in protein expression. Together, these results establish a mechanism for how codon usage regulates mRNA translation efficiency.
ncRNA-eQTL: a database to systematically evaluate the effects of SNPs on non-coding RNA expression across cancer types
Authors: Li Jiang , Xue Yawen , Amin Muhammad Talal , Yang Yanbo , Yang Jiajun , Zhang Wen , Yang Wenqian , Niu Xiaohui , Zhang Hong-Yu , Gong Jing 
Published: August 2019

Abstract
Numerous studies indicate that non-coding RNAs (ncRNAs) have critical functions across biological processes, and single-nucleotide polymorphisms (SNPs) could contribute to diseases or traits through influencing ncRNA expression. However, the associations between SNPs and ncRNA expression are largely unknown. Therefore, genome-wide expression quantitative trait loci (eQTL) analysis to assess the effects of SNPs on ncRNA expression, especially in multiple cancer types, will help to understand how risk alleles contribute toward tumorigenesis and cancer development. Using genotype data and expression profiles of ncRNAs of &gt;8700 samples from The Cancer Genome Atlas (TCGA), we developed a computational pipeline to systematically identify ncRNA-related eQTLs (ncRNA-eQTLs) across 33 cancer types. We identified a total of 6 133 278 and 721 122 eQTL-ncRNA pairs in cis-eQTL and trans-eQTL analyses, respectively. Further survival analyses identified 8312 eQTLs associated with patient survival times. Furthermore, we linked ncRNA-eQTLs to genome-wide association study (GWAS) data and found 262 332 ncRNA-eQTLs overlapping with known disease- and trait-associated loci. Finally, a user-friendly database, ncRNA-eQTL (http://ibi.hzau.edu.cn/ncRNA-eQTL), was developed for free searching, browsing and downloading of all ncRNA-eQTLs. We anticipate that such an integrative and comprehensive resource will improve our understanding of the mechanistic basis of human complex phenotypic variation, especially for ncRNA- and cancer-related studies.
Submaximal Angioplasty for Symptomatic Intracranial Atherosclerotic Disease: A Meta-Analysis of Peri-Procedural and Long-Term Risk
Authors: Stapleton Christopher J , Chen Yi-Fan , Shallwani Hussain , Vakharia Kunal , Turan Tanya N , Woo Henry H , Derdeyn Colin P , Charbel Fady T , Siddiqui Adnan H , Amin-Hanjani Sepideh 
Published: August 2019

Abstract

BACKGROUND
Symptomatic intracranial atherosclerotic disease (ICAD) is an important cause of stroke. Although the high periprocedural risk of intracranial stenting from recent randomized studies has dampened enthusiasm for such interventions, submaximal angioplasty without stenting may represent a safer endovascular treatment option.

OBJECTIVE
To examine the periprocedural and long-term risks associated with submaximal angioplasty for ICAD based on the available literature.

METHODS
All English language studies of intracranial angioplasty for ICAD were screened. Inclusion criteria were as follows: ≥ 5 patients, intervention with submaximal angioplasty alone, and identifiable periprocedural (30-d) outcomes. Analysis was co-nducted to identify the following: 1) periprocedural risk of any stroke (ischemic or hemorrh-agic) or death, and 2) stroke in the territory of the target vessel and fatal stroke beyond 30 d. Mixed effects logistic regression was used to summarize event rates. Funnel plot and rank correlation tests were employed to detect publication bias. The relative risk of periprocedural events from anterior vs posterior circulation disease intervention was also examined.

RESULTS
A total of 9 studies with 408 interventions in 395 patients met inclusion criteria. Six of these studies included 113 posterior circulation interventions. The estimated pooled rate for 30-d stroke or death following submaximal angioplasty was 4.9% (95% CI: 3.2%-7.5%), whereas the estimated pooled rate beyond 30 d was 3.7% (95% CI: 2.2%-6.0%). There was no statistical difference in estimated pooled rate for 30-d stroke or death between patients with anterior (4.8%, 95% CI: 2.8%-7.9%) vs posterior (5.3%, 95% CI: 2.4%-11.3%) circulation disease (P > .99).

CONCLUSION
Submaximal angioplasty represents a potentially promising intervention for symptomatic ICAD.
Influence of Diagnostic Method on Outcomes in Phase 3 Clinical Trials of Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection: A Post Hoc Analysis of MODIFY I/II
Authors: Wilcox Mark H , Rahav Galia , Dubberke Erik R , Gabryelski Lori , Davies Kerrie , Berry Claire , Eves Karen , Ellison Misoo C , Guris Dalya , Dorr Mary Beth 
Published: August 2019

Abstract

Background
The optimum diagnostic test method for Clostridioides difficile infection (CDI) remains controversial due to variation in accuracy in identifying true CDI. This post hoc analysis examined the impact of CDI diagnostic testing methodology on efficacy outcomes in phase 3 MODIFY I/II trials.

Methods
In MODIFY I/II (NCT01241552/NCT01513239), participants received bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment for primary/recurrent CDI (rCDI). Using MODIFY I/II pooled data, initial clinical cure (ICC) and rCDI were assessed in participants diagnosed at baseline using direct detection methods (enzyme immunoassay [EIA]/cell cytotoxicity assay [CCA]) or indirect methods to determine toxin-producing ability (toxin gene polymerase chain reaction [tgPCR]/toxigenic culture).

Results
Of 1554 participants who received bezlotoxumab or placebo in MODIFY I/II, 781 (50.3%) and 773 (49.7%) were diagnosed by tgPCR/toxigenic culture and toxin EIA/CCA, respectively. Participants diagnosed by toxin EIA/CCA were more likely to be inpatients, older, and have severe CDI. In bezlotoxumab recipients, ICC rates were slightly higher in the toxin EIA/CCA subgroup (81.7%) vs tgPCR/toxigenic culture (78.4%). Bezlotoxumab significantly reduced the rCDI rate vs placebo in both subgroups; however, the magnitude of reduction was substantially larger in participants diagnosed by toxin EIA/CCA (relative difference, –46.6%) vs tgPCR/toxigenic culture (–29.1%). In bezlotoxumab recipients, the rCDI rate was lower in the toxin EIA/CCA subgroup (17.6%) vs tgPCR/toxigenic culture (23.6%; absolute difference, –6.0%; 95% confidence interval, –12.4 to 0.3; relative difference, –25.4%).

Conclusions
Diagnostic tests that detect fecal C. difficile toxins are of fundamental importance to accurately diagnosing CDI, including in clinical trial design, ensuring that therapeutic efficacy is not underestimated.
Integrated safety profile of atacicept: an analysis of pooled data from the atacicept clinical trial programme
Authors: Gordon Caroline , Bassi Roberto , Chang Peter , Kao Amy , Jayne David , Wofsy David , Fleuranceau-Morel Patricia 
Published: August 2019

Abstract

Objective
To characterize the overall safety profile of atacicept, we conducted an integrated analysis of pooled safety data from all 17 clinical studies to date.

Methods
Three data sets were used to investigate safety endpoints: a double-blind placebo-controlled set (n = 1568), an SLE set (n = 761) and a full analysis set (n = 1845; including all 17 studies).

Results
Of 1568 patients in the double-blind placebo-controlled-set, 30.8% received placebo, and 8.2, 24.5 and 36.5% received atacicept 25, 75 and 150 mg, respectively. Treatment-emergent adverse event (TEAE) rates (adjusted by treatment-exposure) were generally higher with atacicept vs placebo, but no consistent association was found between atacicept dose and specific TEAEs or mortality. Serious infection and serious TEAE rates were similar for atacicept and placebo. The TEAE-related discontinuation rates were higher with atacicept vs placebo (16.1 vs 10.9/100 patient-years). In the full analysis set, 11 deaths occurred during treatment. Across indications, exposure-adjusted mortality rates/100 patient-years (95% CI) were 3.60 (0.90, 14.38), 0.34 (0.05, 2.43) and 1.18 (0.49, 2.82) with atacicept 25, 75 and 150 mg, respectively, and 0.44 (0.06, 3.12) with placebo. In SLE patients, exposure-adjusted mortality rates were 1.45 (0.54, 3.87) with atacicept 150 mg and 0.78 (0.29, 2.07) across all atacicept-treated patients. No deaths occurred with atacicept 75 mg or placebo. In the SLE and double-blind placebo-controlled sets, pharmacodynamic effects of atacicept were not associated with increased infection rates.

Conclusion
The results of this integrated safety analysis support further development and evaluation of atacicept in selected patients for whom potential benefits might outweigh risks.
Predictors of fatigue in rheumatoid arthritis
Authors: Druce Katie L , Basu Neil 
Published: August 2019

AbstractPeople with RA commonly experience fatigue. Fatigue is a key contributor to increased clinical care costs, primary care consultations and employment loss. Despite this, our understanding of the prognostic of factors of poor fatigue outcomes is lacking and fatigue is poorly managed. Examining longitudinal predictors of fatigue can identify both individuals ‘at risk’ of poor prognosis, and candidate mechanisms that are worthy of greater inspection. This review discusses the factors most commonly investigated as being implicated in the prognosis of RA fatigue. The available data appears to implicate generic factors such as pain, mental health, disability and sleep as consistent predictors of fatigue outcome, while the role of disease activity and inflammation seems less clear. However, the existing data are not without methodological limitations and there have been no specific studies primarily designed to investigate the inflammatory biomarkers of fatigue. Future studies are required to more comprehensively and robustly determine the mechanisms of fatigue.
STAT3 phosphorylation mediates the stimulatory effects of interferon alpha on B cell differentiation and activation in SLE
Authors: De Groof Aurélie , Ducreux Julie , Aleva Floor , Long Andrew J , Ferster Alina , van der Ven Andre , van de Veerdonk Frank , Houssiau Frédéric A , Lauwerys Bernard R 
Published: August 2019

AbstractObjectiveType I IFNs play a well-known role in the pathogenesis of SLE, through activation of CD4 T and antigen-presenting cells. Here, we investigated the effects of IFN alpha (IFNα) on SLE B cell activation and differentiation.MethodsPeripheral blood mononuclear cells (PBMCs) and purified total or naïve B cells were obtained from healthy controls and SLE patients. The effects of IFNα on B cell differentiation were studied by flow cytometry. The role of STAT3 in B cell responses to IFNα was studied using pharmacological inhibitors and PBMCs from STAT3-deficient individuals.ResultsIncubation of normal PBMCs with IFNα induces a B cell differentiation pattern as observed spontaneously in SLE PBMCs. IFNα displays direct stimulatory effects on purified naïve B cells from healthy individuals, as evidenced by a significant induction of cell surface CD38 and CD95 in the presence of the cytokine. In purified naïve B cells, IFNα also induces STAT3 phosphorylation. IFNα-induced naïve B cell differentiation in total PBMCs is significantly inhibited in the presence of STAT3 inhibitors, or in PBMCs from individuals with STAT3 loss of function mutations. Spontaneous levels of STAT3, but not STAT1, phosphorylation are significantly higher in total B cells from SLE patients compared with controls. Pharmacological STAT3 inhibition in SLE PBMCs inhibits naïve B cell activation and differentiation.ConclusionIFNα displays direct stimulatory effects on B cell differentiation and activation in SLE. STAT3 phosphorylation mediates the effects of IFNα stimulation in naïve B cells, an observation that opens new therapeutic perspectives in SLE.
A new subfamily for a clade of opecoelids (Trematoda: Digenea) exploiting marine fishes as second-intermediate hosts, with the first report of opecoelid metacercariae from an elasmobranch
Authors: Martin Storm Blas , Downie Abigail Jayne , Cribb Thomas Herbert 
Published: August 2019

AbstractMetacercariae of trematodes belonging to the family Opecoelidae were collected from small fishes of the Great Barrier Reef: a blenniid, two gobiids, two labrids, three pomacentrids, a monacanthid, an ostraciid and the epaulette shark, Hemiscyllium ocellatum. Sequences of the second internal transcribed spacer region (ITS2) of ribosomal DNA were generated from these metacercariae in an attempt to match them with adult worms. Three species of Allopodocotyle (Allopodocotyle epinepheli, Allopodocotyle heronensis and an unidentified species), two unidentified species of Hamacreadium and Pacificreadium serrani were detected. Among the Opecoelidae, these species all resolve to a single, phylogenetically and somewhat morphologically distinct clade. Species of this clade are the only known marine opecoelids to exploit fishes as second-intermediate hosts. The clade is proposed to warrant a new subfamily, the Hamacreadiinae subfam. nov. It includes Allopodocotyle, Bentholebouria, Cainocreadium, Choanotrema, Hamacreadium, Pacificreadium, Paraplagioporus, Pedunculacetabulum and Podocotyloides.
Application of Artificial Intelligence–based Image Optimization for Computed Tomography Angiography of the Aorta With Low Tube Voltage and Reduced Contrast Medium Volume
Authors: Wang Yining , Yu Min , Wang Ming , Wang Yun , Kong Lingyan , Yi Yan , Wang Man , Li Yumei , Jin Zhengyu 
Published: August 2019

Purpose:
The purpose of this study was to evaluate the impact of artificial intelligence (AI)-based noise reduction algorithm on aorta computed tomography angiography (CTA) image quality (IQ) at 80 kVp tube voltage and 40 mL contrast medium (CM).

Materials and Methods:
After obtaining institutional review board approval and 8 written informed consents, 60 patients (35 men, 25 women; age range: 18 to 85 y) referred for aorta CTA examination were assigned to 2 groups at random. Group A underwent an 80 kVp protocol with 40 mL CM (320 mg I/mL). Group A reconstructed with iterative reconstruction was named as group A1 and further AI-based noise reduction was named as group A2. Group B was scanned with standard 120 kVp, 80 mL CM, and iterative reconstruction algorithm. The quantitative assessment of IQ included aorta CT attenuation, noise, signal-to-noise ratio, and contrast-to-noise ratio. A 5-point scale (5—excellent, 1—poor) was used by 2 radiologists independently for qualitative IQ analysis.

Results:
The image noise significantly decreased while signal-to-noise ratio and contrast-to-noise ratio significantly increased in the order of group A1, B, and A2 (all P<0.05). Compared with group B, the subjective IQ score of group A1 was significantly lower (P<0.05), while that of group A2 had no significant difference (P>0.05). The effective dose and CM volume of group A were reduced by 79.18% and 50%, respectively, than that of group B.

Conclusions:
The AI-based noise reduction could improve the IQ of aorta CTA with low kV and reduced CM, which achieved the potential of radiation dose and contrast media reduction compared with conventional aorta CTA protocol.
Pharmacokinetics of Tranexamic Acid Given as an Intramuscular Injection Compared to Intravenous Infusion in a Swine Model of Ongoing Hemorrhage
Authors: Spruce Marguerite W. , Beyer Carl A. , Caples Connor M. , DeSoucy Erik S. , Kashtan Harris W. , Hoareau Guillaume L. , Grayson J. Kevin , Johnson M. Austin 
Published: August 2019

ABSTRACT

Introduction:
Tranexamic acid (TXA) improves survival in traumatic hemorrhage, but difficulty obtaining intravenous (IV) access may limit its use in austere environments, given its incompatibility with blood products. The bioavailability of intramuscular (IM) TXA in a shock state is unknown. We hypothesized that IM and IV administration have similar pharmacokinetics and ability to reverse in vitro hyperfibrinolysis in a swine-controlled hemorrhage model.

Methods:
Twelve Yorkshire cross swine were anesthetized, instrumented, and subjected to a 35% controlled hemorrhage, followed by resuscitation. During hemorrhage, they were randomized to receive a 1 g IV TXA infusion over 10 min, 1 g IM TXA in two 5 mL injections, or 10 mL normal saline IM injection as a placebo group to assess model adequacy. Serum TXA concentrations were determined using liquid chromatography-mass spectrometry, and plasma samples supplemented with tissue plasminogen activator (tPA) were analyzed by rotational thromboelastometry.

Results:
All animals achieved class III shock. There was no difference in the concentration–time areas under the curve between TXA given by either route. The absolute bioavailability of IM TXA was 97%. IV TXA resulted in a higher peak serum concentration during the infusion, with no subsequent differences. Both IV and IM TXA administration caused complete reversal of in vitro tPA-induced hyperfibrinolysis.

Conclusion:
The pharmacokinetics of IM TXA were similar to IV TXA during hemorrhagic shock in our swine model. IV administration resulted in a higher serum concentration only during the infusion, but all levels were able to successfully correct in vitro hyperfibrinolysis. There was no difference in total body exposure to equal doses of TXA between the two routes of administration. IM TXA may prove beneficial in scenarios where difficulty establishing dedicated IV access could otherwise limit or delay its use.
Cancer cachexia and treatment toxicity
Authors: Chowdhry Shilpa Mukunda , Chowdhry Varun Kumar 
Published: August 2019

Purpose of review
Cancer cachexia is a metabolic disturbance resulting in a loss of skeletal muscle mass that is generally not reversed through traditional nutritional interventions. We review on both the impact of nutritional status on cancer treatment side effects, as well as cancer- specific outcomes.

Recent findings
Cancer-specific cachexia and sarcopenia are associated with increased treatment-associated toxicity, and overall worse cancer-specific outcomes across all cancer types in surgical, chemotherapeutic, and radiotherapeutic populations. Despite the fact that cancer cachexia is generally thought to be irreversible, there is some evidence that nutritional intervention can be helpful.

Summary
Nutritional status is an important factor to consider in determining cancer therapy. Patients with poor nutritional status should be identified prior to the initiation of therapy and be monitored judiciously.
Characteristics of Patients that Substitute Medical Cannabis for Alcohol
Authors: Hayat Assad , Piper Brian J. 
Published: August 2019

AbstractAimsA substitution effect occurs when patients substitute Medical Cannabis (MC) for another drug. Over three-quarters (76.7%) of New England dispensary members reported reducing their use of opioids and two-fifths (42.0%) decreased their use of alcohol after starting MC (Piper et al. 2017). The objective of this exploratory study was to identify any factors which differentiate alcohol substituters from those that do not modify their alcohol use after starting MC (non-substituters).MethodsAmong dispensary patients (N=1,477), over two-thirds with chronic pain, that completed an online survey, 7.4% indicated that they regularly consumed alcohol. Comparisons were made to identify any demographic or health history characteristics which differentiated alcohol substituters (N=47) from non-substituters (N=65). Respondents selected from among a list of 37 diseases and health conditions (e.g. diabetes, sleep disorders) and the total number was calculated.ResultsSubstituters and non-substituters were indistinguishable in terms of sex, age, or prior drug history. Substituters were significantly more likely to be employed (68.1%) than non-substituters (51.1%). Substituters also reported having significantly more health conditions and diseases (3.3±2.0) than non-substituters (2.4±1.4).ConclusionsThis small study offers some insights into the profile of patients whose self-reported alcohol intake decreased following initiation of MC. Alcohol substituters had more other health conditions but also were more likely to be employed which may indicate that they fit a social drinker profile. Additional prospective or controlled research into the alcohol substitution effect following MC with a sample with more advanced alcohol misuse may be warranted.Short summaryA substitution effect with medical cannabis replacing prescription opioids has been reported but less is known for alcohol. This study evaluated characteristics which might differentiate alcohol substituters (N=47) from non-substituters (N=65) among dispensary members. Substituters were significantly more likely to be employed and have more health conditions than non-substituters.