bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of socioeconomic status with incidence and outcomes of acute kidney injury
Authors: Hounkpatin Hilda O , Fraser Simon D S , Johnson Matthew J , Harris Scott , Uniacke Mark , Roderick Paul J
Published: August 2019

Background

Acute kidney injury (AKI) is common and is associated with significant morbidity and mortality. Socioeconomic status may be negatively associated with AKI as some risk factors for AKI such as chronic kidney disease, diabetes and heart failure are socially distributed. This study explored the socioeconomic gradient of the incidence and mortality of AKI, after adjusting for important mediators such as comorbidities.

Methods

Linked primary care and laboratory data from two large acute hospitals in the south of England, sourced from the Care and Health Information Analytics database, were used to identify AKI cases over a 1-year period (2017–18) from a population of 580 940 adults. AKI was diagnosed from serum creatinine patterns using a Kidney Disease: Improving Global Outcomes-based definition. Multivariable logistic regression and Cox proportional hazard models adjusting for age, sex, comorbidities and prescribed medication (in incidence analyses) and AKI severity (in mortality analyses), were used to assess the association of area deprivation (using Index of Multiple Deprivation for place of residence) with AKI risk and all-cause mortality over a median (interquartile range) of 234 days (119–356).

Results

Annual incidence rate of first AKI was 1726/100 000 (1.7%). The risk of AKI was higher in the most deprived compared with the least deprived areas [adjusted odds ratio = 1.79, 95% confidence interval (CI) 1.59–2.01 and 1.33, 95% CI 1.03–1.72 for <65 and >65 year old, respectively] after controlling for age, sex, comorbidities and prescribed medication. Adjusted risk of mortality post first AKI was higher in the most deprived areas (adjusted hazard ratio = 1.20, 95% CI 1.07–1.36).

Conclusions

Social deprivation was associated with higher incidence of AKI and poorer survival even after adjusting for the higher presence of comorbidities. Such social inequity should be considered when devising strategies to prevent AKI and improve care for AKI patients.
A Shrinking Space: A Dynamic Relationship between the Judiciary in a Liberal Society of Hong Kong and a Socialist-Leninist Sovereign State
Authors: Chan Johannes M M
Published: August 2019

Hong Kong provides a unique case study on the roles and functions of the judiciary within an authoritarian or semi-authoritarian sovereign. Under the unique constitutional arrangement in Hong Kong, a liberal common law judiciary in a highly sophisticated modern metropolis is encapsulated within a Socialist-Leninist sovereign regime that ideologically rejects separation of powers, independence of the judiciary and values of individual liberalism. Notwithstanding the sharp ideological differences and the greatly asymmetrical distribution of social, economic and political powers in this One Country, Two Systems constitutional model, it is argued that the relationship between the courts and the authoritarian sovereign power is and has been complex and dynamic. The Hong Kong courts have been able to create their institutional space by establishing an impressive liberal constitutional common law, but that constitutional space is shrinking as the over-zealous sovereign is increasingly assertive of its views on matters that it perceives to be affecting state interests. By examining a series of controversial decisions, this paper argues that there are reasons that the courts could, with creativity and sensitivity, maintain a delicate and balanced relationship with the sovereign without succumbing to the political pressure, but that the greatest threat of independence of the judiciary comes from within the judiciary in internalizing the values of the socialist state.
Traffic-Centric Mesoscopic Analysis of Connectivity in VANETs
Authors: Zarei Mani
Published: August 2019

Vehicular ad hoc networks (VANETs) have emerged as an appropriate class of information propagation technology promising to link us even while moving at high speeds. In VANETs, a piece of information propagates through consecutive connections. In the most previous vehicular connectivity analysis, the provided probability density function of intervehicle distance throughout the wide variety of steady-state traffic flow conditions is surprisingly invariant. But, using a constant assumption, generates approximate communication results, prevents us from improving the performance of the current solutions and impedes designing the new applications on VANETs. Hence, in this paper, a mesoscopic vehicular mobility model in a multilane highway with a steady-state traffic flow condition is adopted. To model a traffic-centric distribution for the spatial per-hop progress and the expected spatial per-hop progress, different intervehicle distance distributions are utilized. Moreover, the expected number of hops, distribution of the number of successful multihop forwarding, the expected time delay and the expected connectivity distance are mathematically investigated. Finally, to model the distribution of the connectivity distances, a set of simplistic closed-form traffic-centric equations is proposed. The accuracy of the proposed model is confirmed using an event-based network simulator as well as a road traffic simulator.
School Social Workers’ Perceptions of Ethical Dilemmas Associated with Electronic Media Use in School Settings
Authors: Keeney Annie Jane
Published: August 2019

Engaging in ethical decision making is foundational to the social work profession. However, ethical responsibilities become unclear with the variety, speed, and exposure that electronically shared information brings to users. This study sought to explore school social workers’ perceptions of the kinds of ethical dilemmas related to electronic media use encountered in practice and whether ethical dilemmas differed by population served (for example elementary, middle, or high school students). Data for this study came from a survey of school social workers (N = 379) who were associated with state chapter affiliates of the School Social Work Association of America. Results indicate that the majority of elementary school social workers experience ethical dilemmas related to electronic media use by students. The article concludes with a discussion of the practice implications for school social work.
Burden and Bad Days Among Mexican-Origin Women Caregivers
Authors: Mendez-Luck Carolyn A , Anthony Katherine P , Guerrero Lourdes R
Published: August 2019

Objectives

This article examines the construct of burden and the use of coping strategies among Mexican-origin caregivers of older adults.

Methods

In-depth semistructured interviews were conducted with 44 Mexican-origin women caregivers living in the East Los Angeles area. Audio files were transcribed and analyzed in Atlas.ti V7.1.8. Data were analyzed using a grounded theory approach.

Results

Caregivers did not typically talk about caregiving as a burden per se; they used other terms for burden that resonated with their experiences. Caregivers viewed caregiving difficulty in physical and emotional terms as it related to specific caregiving circumstances and situations. Caregivers used a variety of coping strategies to get through bad days, including reframing stressful situations to make sense of their circumstances.

Discussion

Findings shed light on the mixed results found in the literature on Latino caregiving burden. Results suggest that Mexican-origin women caregivers have a more nuanced experience of caregiving burden than has been found in prior literature. Results also suggest research using traditional measures of burden may not fully capture situational and cultural distinctions to the extent Mexican-origin caregivers ascribe other language to represent difficult caregiving experiences.
Lipschitz Normal Embedding Among Superisolated Singularities
Authors: Misev Filip , Pichon Anne
Published: August 2019

Any germ of a complex analytic space is equipped with two natural metrics: the outer metric induced by the hermitian metric of the ambient space and the inner metric, which is the associated riemannian metric on the germ. A complex analytic germ is said Lipschitz normally embedded (LNE) if its outer and inner metrics are bilipschitz equivalent. LNE seems to be fairly rare among surface singularities; the only known LNE surface germs outside the trivial case (straight cones) are the minimal singularities. In this paper, we show that a superisolated hypersurface singularity is LNE if and only if its projectivized tangent cone has only ordinary singularities. This provides an infinite family of LNE singularities, which is radically different from the class of minimal singularities.
Analysis of Toxic Metals in Electronic Cigarette Aerosols Using a Novel Trap Design
Authors: Halstead Mary , Gray Naudia , Gonzalez-Jimenez Nathalie , Fresquez Mark , Valentin-Blasini Liza , Watson Clifford , Pappas R Steven
Published: August 2019

Since 2006 the domestic popularity and sales of electronic cigarettes (i.e., electronic nicotine delivery systems or ENDS) have grown rapidly. Although the constituents of the aerosol produced by ENDS have been previously investigated, differences in puff regimens and aerosol trapping schema in published literature often complicate result comparisons and data interpretation. As the ENDS product designs continue to evolve, there is a critical need to develop and validate robust methodologies for laboratory testing, appropriate aerosol generation and trapping media required for accurate determinations of ENDS aerosol metals deliveries. A simple, high metals purity, fluoropolymer trap was developed and validated that meets standard machine puffing regimen (CORESTA Recommended Method 81) specifications and exhibits negligible acid extractable metal backgrounds. Using a standard machine puffing regimen in combination with a fluoropolymer condensation trap, aerosol was generated and collected from select ENDS devices for analysis of chromium, nickel, copper, zinc, cadmium, tin, and lead with triple quadrupole inductively coupled plasma mass spectrometry. Devices tested spanned a range of commercial products, including flavored variants of JUUL pods, refillable tank systems, rechargeable cartridges, and single-use ENDs devices. Results showed that for aerosols generated under a fixed puffing regimen (50 puffs/collection), metal concentrations ranged from below the detection limits (LOD) to 614 ng copper and 339 ng zinc per 10 puffs. Cadmium concentrations were below LOD for all devices tested. Device specific aerosol levels of Sn and Pb ranged from below LOD to low nanogram levels. Cr and Ni were transported in aerosols at levels equivalent to, or slightly higher than in mainstream cigarette smoke using a standard smoking regimen. The generally lower levels of specific metals, Cd and Pb, transmitted in ENDS aerosols compared to mainstream cigarette smoke reflect possible reduction of harm for smokers who substitute the use of ENDS as cessation devices in place of smoking cigarettes.
Sclerosing angiomatoid nodular transformation of the spleen: case report of a metastatic carcinoma-simulating disorder
Authors: Pinheiro João L , Catarino Sara , Duarte Liliana , Ferreira Marta , Simão Rosa , Pinheiro Luís F , Casimiro Carlos
Published: August 2019

Sclerosing angiomatoid nodular transformation (SANT) is a rare nonneoplastic splenic disorder of unknown etiopathogenesis. This condition is usually found incidentally on imaging studies. Because of its similar features, SANT can wrongly be described as metastatic carcinoma. A 61-year-old Caucasian male was referred to our general surgery outpatient clinic regarding unusual splenic nodular formations in a routine abdominal ultrasound. All diagnostic exams performed confirmed metastatic splenic lesions, but no primary tumor was found. A laparoscopic splenectomy was performed for diagnostic purposes. Histopathology revealed SANT. Benign tumors of the spleen are uncommon entities and can easily be mistaken by malignant secondary lesions. The differential diagnosis of SANT should include other vascular lesions as well as metastatic carcinoma and inflammatory pseudotumor. It is widely recommended that a splenectomy should be performed because only by histopathology and immunohistochemistry staining, the definitive diagnosis of SANT can be made.
Italo Calvino’s Six Memos as ethical imperative in J.R. Carpenter’s The Gathering Cloud
Authors: Wright David Thomas Henry
Published: August 2019

In 1985, Italo Calvino wrote a series of lectures (later published as ‘memos’) in which he proposed six values he deemed crucial to literature as it moved into the next millennium: lightness, quickness, ‘crystal’ exactitude, visibility, multiplicity, and consistency. Though never a writer of electronic literature, Calvino has frequently been associated or referenced in relation to digital works. J.R. Carpenter’s web-based work The Gathering Cloud (2016) (hereafter TGC) exhibits Calvino’s values. TGC is informed by Howard’s 1803 Essay on the Modifications of Clouds. Howard’s ‘frontispiece’ and five ‘plates’ are used in Carpenter’s web-based work. Poetry is then superimposed on these repurposed illustrations. Situated ‘within’ the poetry, animated gif collages play. Where Calvino in his memos writes that he considers the virtues of the binary opposites of his values (i.e., weight, lingering, ‘flame’ exactitude, ambiguity, singularity, and inconsistency) no less compelling, Carpenter’s work suggests that Calvino’s values (or rather the absence or removal of their binary opposites) are not only preferable in terms of contemporary literary challenges, but an ethical imperative in relation to environmental impact as it relates to contemporary media, dissemination, and indeed everyday life. In this analysis of TGC, Calvino’s values will be discussed in relation to each of the work’s six sections (i.e., the ‘frontispiece’ and five ‘plates’).
Photometric and kinematic misalignments and their evolution among fast and slow rotators in the illustris simulation
Authors: Yang Lisiyuan , Xu Dandan , Mao Shude , Springel Volker , Li Hongyu
Published: August 2019

We use the Illustris simulation to study the distributions of ellipticities and kinematic misalignments of galactic projections, as well as the intrinsic shapes and rotation of the simulated galaxies. Our results for the projections of galaxies display clear trends of an overall increase of kinematic misalignment and a slight decrease of ellipticity for fast rotators with increasing masses, while revealing no clear distinction between slow rotators of different mass. It is also found that the number of very slow rotators with large ellipticities is much larger than found in observations. The intrinsic properties of the galaxies are then analysed. The results for the intrinsic shapes of the galaxies are mostly consistent with previous results inferred from observational data. The distributions of intrinsic misalignment of the galaxies suggest that some of the galaxies produced by Illustris have significant rotation around their medium axes. Further analysis reveals that most of these galaxies display signs of non-equilibrium. We then study the evolution of the intrinsic misalignments and shapes of three specific Illustris galaxies, which we consider as typical ones, along the main progenitor line of their merger trees, revealing how mergers influence the intrinsic shapes and kinematics: the spin axis in general stays close to the shortest axis, and tends to quickly relax to such an equilibrium state within a few dynamical times of the galaxy after major perturbations; triaxiality and intrinsic flatness in general decrease with time, however, sometimes increases occur that are clearly seen to correlate with major merger events.
Are there broad absorption-line blazars?
Authors: Mishra Sapna , Krishna Gopal , Chand Hum , Chand Krishan , Ojha Vineet
Published: August 2019

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

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

Codon 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

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 >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

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

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

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

People 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

Objective

Type 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.

Methods

Peripheral 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.

Results

Incubation 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.

Conclusion

IFNα 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

Metacercariae 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

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.

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

Aims

A 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).

Methods

Among 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.

Results

Substituters 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).

Conclusions

This 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 summary

A 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.
Addressing the Embeddability Problem in Transition Rate Estimation
Authors: Goolsby Curtis , Losey James , Xu Yuchen , Düker Marie-Christine , Sherman Mila Getmansky , Matteson David S. , Moradi Mahmoud
Published: August 2019

Markov State Models (MSM) and related techniques have gained significant traction as a tool for analyzing and guiding molecular dynamics (MD) simulations due to their ability to extract structural, thermodynamic, and kinetic information on proteins using computationally feasible MD simulations. The MSM analysis often relies on spectral decomposition of empirically generated transition matrices. Here, we discuss an alternative approach for extracting the thermodynamic and kinetic information from the so-called rate/generator matrix rather than the transition matrix. Although the rate matrix itself is built from the empirical transition matrix, it provides an alternative approach for estimating both thermodynamic and kinetic quantities, particularly in diffusive processes. We particularly discuss a fundamental issue with this approach, known as the embeddability problem and offer ways to address this issue. We describe eight different methods to overcome the embeddability problem, including a novel approach developed for this work. The algorithms were tested on data from a one-dimensional toy model to show the workings of these methods and discuss the robustness of each method in terms of its dependence in lag time and trajectory length.
LARP1 facilitates translational recovery after amino acid refeeding by preserving long poly(A)-tailed TOP mRNAs
Authors: Ogami Koichi , Oishi Yuka , Nogimori Takuto , Sakamoto Kentaro , Hoshino Shin-ichi
Published: August 2019

Occasionally, cells must adapt to an inimical growth conditions like amino acid starvation (AAS) by downregulating protein synthesis. A class of transcripts containing 5’terminal oligopyrimidine (5’TOP) motif encodes translation-related proteins such as ribosomal proteins (RPs) and elongation factors, and therefore, their translation is severely repressed during AAS to conserve energy1. The RNA-binding protein LARP1 transduces amino acid signaling to TOP gene expression by controlling translation and stability of TOP mRNAs2-6. When released from AAS, translation machineries in turn have to be restored, however, the underlying mechanism of such re-adaptation is largely unknown. Here we show that LARP1 preserves TOP mRNAs in a long polyadenylated state during long-term AAS. We found that TOP mRNAs become highly polyadenylated when cells are in AAS or treated with the mTOR (mechanistic target of rapamycin) inhibitor Torin1. Importantly, depletion of LARP1 completely abrogated the polyadenylation of TOP mRNAs. Comprehensive analysis of poly(A) tail length using the Nanopore direct RNA sequencing revealed that TOP mRNAs are selectively polyadenylated under mTOR inhibition. Since a long poly(A) tail confers increased stability and polysome formation of TOP mRNAs, we predict that LARP1-dependent preservation of TOP mRNAs enables rapid translational resumption after the release from AAS.
Saccadic adaptation in the presence of artificial central scotomas
Authors: Song Youngmin , Ouchene Lydia , Khan Aarlenne Z.
Published: August 2019

Saccadic adaptation can occur over a short period of time through a constant adjustment of the saccade target during the saccade, resulting in saccadic re-referencing which directs the saccade to a location different from the target that elicited the saccade. Saccade re-referencing could be used to help patients with age-related macular degeneration (AMD) to optimally use their residual visual function. However, it remains unknown whether saccade adaptation can take place in the presence of central scotomas (i.e., without central vision).

We tested participants in two experiments in a conventional double-step paradigm with a central gaze-contingent artificial scotoma. Experiment 1 (N= 12) comprised a backward adaptation paradigm with a visible and an invisible 3° diameter scotomas. Experiment 2 (N= 13) comprised a forward adaptation paradigm with invisible 2° and 4° diameter scotomas.

In Experiment 1, we observed significant adaptation in both the visible and invisible scotoma conditions comparable to the control condition with no scotoma. This was the case even when the saccade landed such that the target was occluded by the scotoma. We observed that adaptation occurred based on peripheral viewing of the stepped target during the deceleration period.

In Experiment 2, we found that both scotoma conditions showed adaptation again comparable to the control condition with no scotoma. We conclude that saccadic adaptation can occur with central scotomas, showing that it does not require central vision and is driven primarily by peripheral retinal error.
Bee visitation and fruit quality in berries under protected cropping vary along the length of polytunnels
Authors: Hall Mark , Jones Jeremy , Rocchetti Maurizio , Wright Derek , Rader Romina
Published: August 2019

Wild and managed bees provide effective crop pollination services worldwide. Protected cropping conditions are thought to alter the ambient environmental conditions in which pollinators forage for flowers, yet few studies have compared conditions at the edges and centre of growing tunnels. We measured environmental variables (temperature, relative humidity, wind speed, white light and UV light) and surveyed the activity of managed honeybeesApis mellifera, wild stingless beesTetragonula carbonariaand sweat beesHomalictus urbanusalong the length of 32 multiple open-ended polyethylene growing tunnels. These were spaced across 12 blocks at two commercial berry farms, in Coffs Harbour, New South Wales and Walkamin, North Queensland, Australia. Berry yield, fresh weight and other quality metrics were recorded at discrete increments along the length of the tunnels. We found a higher abundance and greater number of flower visits by stingless bees and honeybees at the end of tunnels, and less frequent visits to flowers toward the middle of tunnels. The centre of tunnels experienced higher temperatures and reduced wind speed. In raspberry, fruit shape was improved with greater pollinator abundance and was susceptible to higher temperatures. In blueberry, per plant yield and mean berry weight were positively associated with pollinator abundance and were lower at the centre of tunnels than at the edge. Fruit quality (crumbliness) in raspberries was improved with a greater number of visits by sweat bees, who were not as susceptible to climatic conditions within tunnels. Understanding bee foraging behaviour and changes to yield under protected cropping conditions is critical to inform the appropriate design of polytunnels and aid pollinator management within them.
Gi-Coupled Receptor Activation Potentiates Piezo2 Currents via Gβγ
Authors: Del Rosario John Smith , Yudin Yevgen , Su Songxue , Hartle Cassandra , Mirshahi Tooraj , Rohacs Tibor
Published: August 2019

Dysregulation of mechanosensitive Piezo2 channels is a hallmark of mechanical allodynia, yet the cellular mechanisms that sensitize mechanoreceptors are still poorly understood. Activation of Gi-coupled receptors sensitizes Piezo2 currents, but whether Gi-coupled receptors regulate the activity of Piezo2 channels is not known. Here, we found that activation of Gi-coupled receptors potentiates Piezo2 currents in dorsal root ganglion (DRG) neurons and in heterologous systems, but inhibits Piezo1 currents in heterologous systems. The potentiation, or inhibition of Piezo currents is abolished when blocking Gβγ with the c-terminal domain of the beta-adrenergic kinase (βARKct). Pharmacological inhibition of kinases downstream of Gβγ, phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), also abolished the potentiation of Piezo2 currents. Hence, our studies illustrate an indirect mechanism of action of Gβγ to sensitize Piezo2 currents after activation of Gi-coupled receptors.