bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-reported outcomes in symptom-driven remote arrhythmia monitoring: evaluation of the Dutch HartWacht-telemonitoring programme
Authors: Kolk Maarten Z H , Blok Sebastiaan , De Wildt Maud C C , Tjong Fleur V Y , Winter Michiel M , Tulevski Igor I , van den Born Bert-Jan H , Somsen G Aernout
Published: March 2021

Aims

There is limited quantitative evidence on the effect of symptom-driven telemonitoring for cardiac arrhythmias on patient-reported outcomes. We evaluated the effect of a symptom-driven remote arrhythmia monitoring programme on the patient-reported health-related quality of life (HRQoL), sense of safety, physical limitations, and self-management.

Methods and results

This was an observational retrospective longitudinal study of the symptom-driven HartWacht-telemonitoring programme using a remote single-lead electrocardiogram monitoring system. Real-world patient data from participants who were enrolled in the telemonitoring programme for (suspected) symptomatic atrial fibrillation (AF) between July 2017 and September 2019 were evaluated. Primary outcomes were the patient-reported generic HRQoL, disease-specific HRQoL, sense of safety, physical limitations, and self-management at date of enrolment, 3 months and 6 months of follow-up. Outcomes were compared to a historical control group consisting of AF patients receiving standard care. A total of 109 participants in the HartWacht programme [59 men (54%); mean age 61 ± 11 years; 72% diagnosed AF] were included in complete case analysis. There was no significant change in HRQoL and sense of safety during follow-up. A significant improvement in the perceived physical limitations was observed. The level of self-management declined significantly during follow-up. Comparisons to the historic control group (n = 83) showed no difference between the patient-reported disease-specific HRQoL, sense of safety and physical limitations at 6 months of follow-up.

Conclusion

Symptom-driven remote arrhythmia monitoring for AF does not seem to affect HRQoL and sense of safety, whereas the perceived physical limitations tend to improve. Patient-reported self-management declined during the first 6 months of participation.
LI Detector: a framework for sensitive colony-based screens regardless of the distribution of fitness effects
Authors: Parikh Saurin Bipin , Castilho Coelho Nelson , Carvunis Anne-Ruxandra
Published: March 2021

Microbial growth characteristics have long been used to investigate fundamental questions of biology. Colony-based high-throughput screens enable parallel fitness estimation of thousands of individual strains using colony growth as a proxy for fitness. However, fitness estimation is complicated by spatial biases affecting colony growth, including uneven nutrient distribution, agar surface irregularities, and batch effects. Analytical methods that have been developed to correct for these spatial biases rely on the following assumptions: (1) that fitness effects are normally distributed, and (2) that most genetic perturbations lead to minor changes in fitness. Although reasonable for many applications, these assumptions are not always warranted and can limit the ability to detect small fitness effects. Beneficial fitness effects, in particular, are notoriously difficult to detect under these assumptions. Here, we developed the linear interpolation-based detector (LI Detector) framework to enable sensitive colony-based screening without making prior assumptions about the underlying distribution of fitness effects. The LI Detector uses a grid of reference colonies to assign a relative fitness value to every colony on the plate. We show that the LI Detector is effective in correcting for spatial biases and equally sensitive toward increase and decrease in fitness. LI Detector offers a tunable system that allows the user to identify small fitness effects with unprecedented sensitivity and specificity. LI Detector can be utilized to develop and refine gene–gene and gene–environment interaction networks of colony-forming organisms, including yeast, by increasing the range of fitness effects that can be reliably detected.
Chemosensory signal transduction inCaenorhabditis elegans
Authors: Ferkey Denise M , Sengupta Piali , L’Etoile Noelle D
Published: March 2021

Chemosensory neurons translate perception of external chemical cues, including odorants, tastants, and pheromones, into information that drives attraction or avoidance motor programs. In the laboratory, robust behavioral assays, coupled with powerful genetic, molecular and optical tools, have made Caenorhabditis elegans an ideal experimental system in which to dissect the contributions of individual genes and neurons to ethologically relevant chemosensory behaviors. Here, we review current knowledge of the neurons, signal transduction molecules and regulatory mechanisms that underlie the response of C. elegans to chemicals, including pheromones. The majority of identified molecules and pathways share remarkable homology with sensory mechanisms in other organisms. With the development of new tools and technologies, we anticipate that continued study of chemosensory signal transduction and processing in C. elegans will yield additional new insights into the mechanisms by which this animal is able to detect and discriminate among thousands of chemical cues with a limited sensory neuron repertoire.
Dri1 mediates heterochromatin assembly via RNAi and histone deacetylation
Authors: Ban Hyoju , Sun Wenqi , Chen Yu-hang , Chen Yong , Li Fei
Published: March 2021

Heterochromatin, a transcriptionally silenced chromatin domain, is important for genome stability and gene expression. Histone 3 lysine 9 methylation (H3K9me) and histone hypoacetylation are conserved epigenetic hallmarks of heterochromatin. In fission yeast, RNA interference (RNAi) plays a key role in H3K9 methylation and heterochromatin silencing. However, how RNAi machinery and histone deacetylases (HDACs) are coordinated to ensure proper heterochromatin assembly is still unclear. Previously, we showed that Dpb4, a conserved DNA polymerase epsilon subunit, plays a key role in the recruitment of HDACs to heterochromatin during S phase. Here, we identified a novel RNA-binding protein Dri1 that interacts with Dpb4. GFP-tagged Dri1 forms distinct foci mostly in the nucleus, showing a high degree of colocalization with Swi6/Heterochromatin Protein 1. Deletion of dri1+ leads to defects in silencing, H3K9me, and heterochromatic siRNA generation. We also showed that Dri1 physically associates with heterochromatic transcripts, and is required for the recruitment of the RNA-induced transcriptional silencing (RITS) complex via interacting with the complex. Furthermore, loss of Dri1 decreases the association of the Sir2 HDAC with heterochromatin. We further demonstrated that the C-terminus of Dri1 that includes an intrinsically disordered (IDR) region and three zinc fingers is crucial for its role in silencing. Together, our evidences suggest that Dri1 facilitates heterochromatin assembly via the RNAi pathway and HDAC.
Anthropometric Variables as Mediators of the Association of Changes in Diet and Physical Activity With Inflammatory Profile
Authors: Cárdenas-Fuentes Gabriela , Lassale Camille , Martínez-González Miguel Ángel , Grau María , Salas-Salvadó Jordi , Corella Dolores , Serra-Majem Lluis , Warnberg Julia , Konieczna Jadwiga , Estruch Ramón , Pintó Xavier , Martínez J Alfredo , Vázquez Clotilde , Vidal Josep , Tur Josep A , Díaz-López Andrés , Lancova Hana , Fito Montserrat , Schröder Helmut
Published: March 2021

Background

Mechanisms underlying the associations of high levels of physical activity (PA) and adherence to the Mediterranean diet (MedDiet) with a better inflammatory profile remain unclear. Our objective was to assess the mediating role of changes in body mass index (BMI) and waist circumference (WC), as markers of body fat in the association of changes in PA and adherence to the MedDiet, with changes in the inflammatory profile.

Method

This study included 489 adults, aged 55–75 years, from the PREDIMED-Plus multicenter lifestyle intervention trial. An inflammatory score was calculated, based on 8 blood biomarkers: high-sensitivity C-reactive protein, interleukin 6, interleukin 8, interleukin 18, monocyte chemo-attractant protein-1, C-peptide, leptin, and regulated on activation, normal T-cell–expressed and secreted chemokine. Biomarkers, levels of PA, score of MedDiet adherence, BMI, and WC were measured at baseline and at 1-year follow-up. Linear regression models were fitted according to the Baron and Kenny framework for mediation analysis.

Results

Changes in BMI and WC mediated the association of both changes in PA and changes in the MedDiet adherence with the inflammatory score. Body mass index mediated 26% of the association of changes in total PA with the inflammatory profile, and 27% of the association of changes in the MedDiet, while WC mediated 13% and 12% of these associations, respectively.

Conclusion

In older adults at high cardiovascular risk, increasing PA levels and adherence to a MedDiet during 1 year were associated with a lower inflammatory score, which was partly mediated by a reduction in body fat.

Clinical Trials Registration Number

International Standard Randomized Controlled Trial Number: ISRCTN89898870; registration date July 24, 2014, retrospectively registered.
Reduced Physical Activity Alters the Leucine-Stimulated Translatome in Aged Skeletal Muscle
Authors: Mahmassani Ziad S , McKenzie Alec I , Petrocelli Jonathan J , de Hart Naomi M , Fix Dennis K , Kelly Joshua J , Baird Lisa M , Howard Michael T , Drummond Micah J
Published: March 2021

Periods of inactivity experienced by older adults induce nutrient anabolic resistance creating a cascade of skeletal muscle transcriptional and translational aberrations contributing to muscle dysfunction. The purpose of this study was to identify how inactivity alters leucine-stimulated translation of molecules and pathways within the skeletal muscle of older adults. We performed ribosomal profiling alongside RNA sequencing from skeletal muscle biopsies taken from older adults (n = 8; ~72 years; 6 F/2 M) in response to a leucine bolus before (Active) and after (Reduced Activity) 2 weeks of reduced physical activity. At both visits, muscle biopsies were taken at baseline, 60 minutes (early response), and 180 minutes (late response) after leucine ingestion. Previously identified inactivity-related gene transcription changes (PFKFB3, GADD45A, NMRK2) were heightened by leucine with corresponding changes in translation. In contrast, leucine also stimulated translational efficiency of several transcripts in a manner not explained by corresponding changes in mRNA abundance (“uncoupled translation”). Inactivity eliminated this uncoupled translational response for several transcripts, and reduced the translation of most mRNAs encoding for ribosomal proteins. Ingenuity Pathway Analysis identified discordant circadian translation and transcription as a result of inactivity such as translation changes to PER2 and PER3 despite unchanged transcription. We demonstrate inactivity alters leucine-stimulated “uncoupled translation” of ribosomal proteins and circadian regulators otherwise not detectable by traditional RNA sequencing. Innovative techniques such as ribosomal profiling continues to further our understanding of how physical activity mediates translational regulation, and will set a path toward therapies that can restore optimal protein synthesis on the transcript-specific level to combat negative consequences of inactivity on aging muscle.
Eikonal equation-basedP-wave seismic azimuthal anisotropy tomography of the crustal structure beneath northern California
Authors: Liu Yongsheng , Tong Ping
Published: March 2021

Delineating spatial variations of seismic anisotropy in the crust is of great importance for the understanding of structural heterogeneities, regional stress regime and ongoing crustal dynamics. In this study, we present a 3-D anisotropic P-wave velocity model of the crust beneath northern California by using the eikonal equation-based seismic azimuthal anisotropy tomography method. The velocity heterogeneities under different geological units are well resolved. The thickness of the low-velocity sediment at the Great Valley Sequence is estimated to be about 10 km. The high-velocity anomaly underlying Great Valley probably indicates the existence of ophiolite bodies. Strong velocity contrasts are revealed across the Hayward Fault (2–9 km) and San Andreas Fault (2–12 km). In the upper crust (2–9 km), the fast velocity directions (FVDs) are generally fault-parallel in the northern Coast Range, which may be caused by geological structure; while the FVDs are mainly NE–SW in Great Valley and the northern Sierra Nevada possibly due to the regional maximum horizontal compressive stress. In contrast, seismic anisotropy in the mid-lower crust (12–22 km) may be attributed to the alignment of mica schists. The anisotropy contrast across the San Andreas Fault may imply different mechanisms of crustal deformation on the two sides of the fault. Both the strong velocity contrasts and the high angle (∼45° or above) between the FVDs and the strikes of faults suggest that the faults are mechanically weak in the San Francisco bay area (2–6 km). This study suggests that the eikonal equation-based seismic azimuthal anisotropy tomography is a valuable tool to investigate crustal heterogeneities and tectonic deformation.
New directions for leader personality research: breaking bad in foreign policy
Authors: Kaarbo Juliet
Published: March 2021

This article considers how leaders' personality traits change over time. I focus on how leaders become more authoritarian, overconfident and more mistake-prone; how, when and why do leaders ‘break bad’? Temporal evolution of leaders is an important topic given the long tenure of many political leaders and the influence these leaders have over policies, including foreign policies. There is very little work on how leaders' personalities develop and how they interact with changing constraints and opportunities. This article is an agenda-setting review, designed to push foreign policy analysis in new directions. This is especially important given the resurgence in research on personalities and the renewed interest in leaders. Drawing on diverse and multi-disciplinary scholarship on the psychological effects of aging, experience, learning and power-holding, this article develops expectations about leader personality change. I discuss challenges for research in this area, focusing on how ‘bad’ can be conceptualized, and offer specific avenues for future investigations.
Populism, nationalism and revisionist foreign policy
Authors: Jenne Erin K
Published: March 2021

Over the past decade, we have seen the rise of populist nationalist heads of state across a number of important electoral democracies—all of whom have made some version of the promise to make their countries ‘great again’. However, scholars are divided over whether these leaders' sometimes bombastic rhetoric has consistent or predictable effects on state foreign policy. This article introduces a framework for mapping the effects of populism and nationalism in foreign policy. In doing so, it draws on Essex School discourse analysis and sociological frame analysis to argue that representational crises at the sub-state level increase the popular resonance of ‘sovereigntist frames’ that diagnose the causes of perceived gaps in representation of the ‘authentic’ sovereign community at the international level and enjoin chief executives to resolve these gaps through revisionist foreign policy practices. The ethno-nationalist master frame prescribes policies and practices of lateral revisionism (conflict with neighbours or rival states), the populist frame prescribes systemic revisionism (conflict with allies and the international ‘establishment’), while the ethno-populist frame prescribes omni-revisionism (conflict with both). The article illustrates the effects of these disparate sovereigntist movements across three paired case-studies drawn from Europe, Latin America and the United States. It concludes that nationalism has greater destructive effects for the international system when combined with populism, demonstrating the importance of distinguishing nationalism and populism conceptually in order to isolate their separate and combined effects on foreign policy.
Targeting Immune Cell Metabolism in the Treatment of Inflammatory Bowel Disease
Authors: Zaiatz Bittencourt Vanessa , Jones Fiona , Doherty Glen , Ryan Elizabeth J
Published: March 2021

The cells of the immune system are highly dynamic, constantly sensing and adapting to changes in their surroundings. Complex metabolic pathways govern leukocytes’ ability to fine-tune their responses to external threats. Mammalian target of rapamycin complex 1 and hypoxia inducible factor are important hubs of these pathways and play a critical role coordinating cell activation and proliferation and cytokine production. For this reason, these molecules are attractive therapeutic targets in inflammatory disease. Insight into perturbations in immune cell metabolic pathways and their impact on inflammatory bowel disease (IBD) progression are starting to emerge. However, it remains to be determined whether the aberrations in immune metabolism that occur in gut resident immune cells contribute to disease pathogenesis or are reflected in the peripheral blood of patients with IBD. In this review, we explore what is known about the metabolic profile of T cells, monocytes, macrophages, dendritic cells, and natural killer cells in IBD and discuss the potential of manipulating immune cell metabolism as a novel approach to treating IBD.
Shareholders’ greed and corporate value growth
Authors: Teti Emanuele , Gori Leonella , Magnanini Veronica
Published: March 2021

This article investigates whether companies with a higher payout ratio make fewer investments, to evaluate how firms make their decisions about corporate value creation. Furthermore, it examines how this yearning for dividends and the corresponding earning distribution affect the value creation for the shareholders in the long term. The findings show that companies with a higher level of dividends make fewer investments and deliver a lower return for shareholders. Higher levels of dividends generally imply a lower amount of resources to reinvest, negatively affecting long-term growth investing. Overall, the main insight is that the investor’s “greed” and appetite for short-term results (in forms of dividends), drove a lower performance and creation of value for the same shareholders. The companies more oriented to the long term, in terms of investments and growth, reached a superior value.
An overview of CAR T-cell clinical trial activity to 2021
Authors: Adami Antonella , Maher John
Published: March 2021

Immunotherapy of cancer using chimeric antigen receptor-engineered T-cells has transformed the management of selected haematological malignancies, triggering intense clinical trial activity in this arena. This article summarises trial activity that has been published to date across the spectrum of haematological and solid tumour types.
Positivity of Curvature On Manifolds With Boundary
Authors: Chow Tsz-Kiu Aaron
Published: March 2021

Consider a compact manifold $M$ with smooth boundary $\partial M$. Suppose that $g$ and $\tilde{g}$ are two Riemannian metrics on $M$. We construct a family of metrics on $M$ that agrees with $g$ outside a neighborhood of $\partial M$ and agrees with $\tilde{g}$ in a neighborhood of $\partial M$. We prove that the family of metrics preserves various natural curvature conditions under suitable assumptions on the boundary data. Moreover, under suitable assumptions on the boundary data, we can deform a metric to one with totally geodesic boundary while preserving various natural curvature conditions.
Trace amounts of antibiotic exacerbated diarrhea and systemic
inflammation of weaned pigs infected with a pathogenic Escherichia
coli
Authors: Kim Kwangwook , He Yijie , Jinno Cynthia , Kovanda Lauren , Li Xunde , Song Minho , Liu Yanhong
Published: March 2021

The experiment was conducted to investigate the effects of trace amounts of antibiotic on growth performance, diarrhea, systemic immunity, and intestinal health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli. Weaned pigs (n = 34, 6.88 ± 1.03 kg body weight [BW]) were individually housed in disease containment rooms and randomly allotted to one of the three dietary treatments: nursery basal diet (CON) and two additional diets supplemented with 0.5 or 50 mg/kg carbadox to the nursery basal diet (TRA or REC), respectively. The experiment lasted 18 d with 7 d before and 11 d after the first E. coli inoculation. The E. coli F18 inoculum was orally provided to all pigs with a dose of 1010 colony-forming unit (CFU)/3 mL for three consecutive days. Fecal and blood samples were collected on day 0 before inoculation and days 2, 5, 8, and 11 postinoculation (PI) to test the percentage of β-hemolytic coliforms in total coliforms and complete blood cell count, respectively. Sixteen pigs were euthanized on day 5 PI, whereas the remaining pigs were euthanized at the end of the experiment to collect the jejunal and ileal mucosa and mesenteric lymph node for gene expression and bacterial translocation, respectively. Pigs in REC had greater (P < 0.05) final BW and lower (P < 0.05) overall frequency of diarrhea compared with pigs in the CON and TRA groups. Pigs in TRA had the lowest (P < 0.05) average daily gain and feed efficiency from day 0 to 5 PI, highest (P < 0.05) percentage of β-hemolytic coliforms in fecal samples on days 2 and 5 PI, and greatest (P < 0.05) bacterial colonies in mesenteric lymph nodes on day 11 PI compared with pigs in the CON and REC groups. Pigs in TRA had the greatest (P < 0.05) neutrophils on day 5 PI and higher (P < 0.05) white blood cell counts and lymphocytes than other groups on day 11 PI. Pigs in TRA had the greatest (P < 0.05) serum C-reactive protein on days 2 and 5 PI and serum tumor necrosis factor-α on day 5 PI, compared with pigs in the CON and REC groups. Pigs fed REC had increased (P < 0.05) mRNA expression of zona occludens-1 (ZO-1) and occludin (OCDN) and reduced (P < 0.05) interleukin-1 beta (IL1B), interleukin-6 (IL6), and tumor necrosis factor-alpha (TNFA) in ileal mucosa on day 5 PI, compared with the CON, whereas TRA upregulated (P < 0.05) mRNA expression of IL1B, IL6, and cyclooxygenase-2 (COX2) in the ileal mucosa on day 11 PI, compared with the REC. In conclusion, trace amounts of antibiotic may exacerbate the detrimental effects of E. coli infection on pig performance by increasing diarrhea and systemic inflammation of weanling pigs.
Inhibition of prolactin promotes secondary skin follicle activation in cashmere goats
Authors: Zhang Lechao , Duan Chunhui , Guo Yunxia , Zhang Yingjie , Liu Yueqin
Published: March 2021

The aim of this study was to investigate the involvement of prolactin (PRL) on development of secondary skin follicles in cashmere goats. Goats were randomly assigned to either a bromocriptine treatment or control group. Samples of cashmere fiber, blood, and skin were collected from all goats after 1 mo. The results indicated that the length, growth rate, and diameter of fibers were not influenced (P > 0.05) by the inhibition of PRL resulting from the treatment with bromocriptine. There was a tendency for increases in total follicle number, primary and secondary follicle numbers, and in the ratio of secondary to primary follicles following treatment with bromocriptine, but these differences were not significant (P > 0.05). The percentage of active secondary follicles in anagen was increased (P < 0.05) in the bromocriptine-treated goats, but there was no effect of treatment on the percentage of active primary follicles. Bromocriptine decreased (P < 0.05) circulating concentrations of PRL and Insulin-like growth factor 1 (IGF1) and increased (P < 0.05) those of melatonin (MT), but there was no effect of this treatment on the serum concentrations of cortisol, growth hormone, tetraiodothyronine, and triiodothyronine. In bromocriptine-treated goats, mRNA expressions of PRL and MT membrane receptor 1a (MTNR1a) were decreased (P < 0.05) and mRNA expression of MT nuclear receptor (RORα) was increased (P < 0.05), but there was no effect of the treatment on expression of long PRL receptor, short PRL receptor, MT membrane receptor 1b and IGF1. It is concluded that inhibition of PRL promotes secondary hair follicle development in the anagen phase, possibly by downregulating MTNR1a and up-regulating RORα gene expression in the skin.
How Do Platforms Empower Consumers? Insights from the Affordances and Constraints of Reclame Aqui
Authors: Kozinets Robert V , Ferreira Daniela Abrantes , Chimenti Paula
Published: March 2021

Consumer feedback platforms offer consumers tools to provide feedback on their market and consumption experiences. Beyond broad prior characterizations, little is known about the specific means by which platforms affect empowerment. Elements of empowerment identified in extant studies include voice, choice, justice, inclusion, catalysis, and consciousness-raising. We research a popular Brazilian platform to learn how platforms facilitate and constrain consumer empowerment. Our approach is immersive, a more-than-human netnography of the platform involving depth interviews with twenty-one of its consumer and corporate users. Findings show same-side and cross-side network effects driving the ability of the platform to offer consumers empowerment. Furthermore, affordances are critically important. Affordances provide opportunities for consumer choice, voice, justice, and inclusion. However, platforms’ cross-side network effects create economic considerations that limit those opportunities in theoretically and practically important ways. Although other feedback platforms might offer catalysis and consciousness-raising elements of empowerment, our focal platform does not. Earlier studies of consumer empowerment on the Internet may have been overly general and exuberant because they failed to recognize the constraining impacts of network effects, affordances, and algorithms. Consumer-citizenry, collective action, and consumer power are thoroughly transformed in the age of the platform, opening up new spaces for further investigation.
Comparative Virulence ofMetarhizium anisopliaeand Four Strains ofBeauveria bassianaAgainst House Fly (Diptera: Muscidae) Adults With Attempted Selection for Faster Mortality
Authors: White Roxie L , Geden Christopher J , Kaufman Phillip E , Johnson Dana
Published: March 2021

Entomopathogenic fungi such as Beauveria bassiana (Balsamo) Vuillemin and Metarhizium anisopliae/brunneum (Metchnikoff)/Petch have shown promising results for managing the house fly, Musca domestica L. A primary challenge of using these biological control agents (BCAs) in field situations is the time required to induce high adult house fly mortality, typically 6–7 d post-exposure. In this study, virulence of M. anisopliae (strain F52) and four B. bassiana strains were compared. The B. bassiana strains GHA and HF23 are used in commercial products and those were compared with two strains that were isolated from house flies on dairy farms (NFH10 and L90). Assays were conducted by exposing adult house flies to fungal-treated filter paper disks for 2 h. The lethal time to 50% mortality (LT50) at the high concentration of 1 × 109 conidia ranged from 3.8 to 5.2 d for all five strains. GHA, NFH10, and L90 killed flies faster than M. anisopliae strain F52; HF23 did not differ from either the M. anisopliae or the other B. bassiana strains. Attempts with the NFH10 strain to induce faster fly mortality through selection across 10 fungal to fly passages did not result in shorter time to fly death of the selected strain compared with the unselected strain.
α-Glucosidase and advanced glycation end products inhibition with Vernonia amygdalina root and leaf extracts: new data supporting the antidiabetic properties
Authors: Medjiofack Djeujo Francine , Cusinato Federico , Ragazzi Eugenio , Froldi Guglielmina
Published: March 2021

Objective

This study aims to investigate antidiabetic activity of several Vernonia amygdalina extracts to study their potential use in medicine.

Methods

Aqueous and ethanol extracts were obtained by maceration and Soxhlet extraction from roots and leaves of V. amygdalina. The extracts were tested as inhibitors of α-glucosidase activity and of advanced glycation end products (AGEs) formation. Further, radical scavenging activity was examined detecting the oxygen radical absorbance capacity, while the potential cytotoxicity of extracts was estimated with MTT assay.

Key findings

In aqueous and ethanol extracts, several polyphenolic compounds were identified; in detail, (-)-catechin and luteolin were found in leaf extracts, while caffeic acid, chlorogenic acid and the terpenoid vernodalol were recognized in root extracts. Regarding antidiabetic activity, the aqueous root extracts efficiently inhibited α-glucosidase activity in a concentration-dependent manner (IC50 = 5.6 µg/ml and 39.8 µg/ml, respectively of macerated and Soxhlet extracts), whereas those obtained from leaves exhibited lower potency. Furthermore, AGEs formation was reduced by all V. amygdalina extracts starting from 10 µg/ml.

Conclusions

The aqueous extracts of V. amygdalina roots obtained by maceration and Soxhlet extraction show remarkable anti-α-glucosidase activity, and all extracts have favourable antiglycation and antioxidant activities.
Hilarious Homicides: Satirizing Sensational Murders in Late Nineteenth-Century London
Authors: Michael-Berger Lee
Published: March 2021

Whereas many studies consider the nineteenth-century fascination with murder as synonymous with the contemporary cultural tendency towards sensation and melodrama, this article offers a fresh perspective on the subject. Here, I deal with a corpus of humorous murder representations, which have rarely been addressed before. I examine how murder was comically represented and look at the contemporary discourse on murder, through the investigation of sources including music hall songs, cartoons, and theatrical travesties, with an emphasis on visual representations. In the context of the democratization of culture, the article examines the importance of murder in the elite claim to cultural authority versus its perception of plebian taste. It demonstrates how late nineteenth-century notions of modernity, which were crystallized through the discussion of murder, were classed and gendered. Thus, a hidden discourse is exposed, in which murder serves as a central tool in a mechanism similar to Bourdieu’s theory of distinction, where cultural and artistic ‘taste’ has a social dimension.
Transcriptomics reveal new insights into molecular regulation of nitrogen use efficiency inSolanum melongena
Authors: Mauceri Antonio , Abenavoli Maria Rosa , Toppino Laura , Panda Sayantan , Mercati Francesco , Aci Meriem Miyassa , Aharoni Asaph , Sunseri Francesco , Rotino Giuseppe Leonardo , Lupini Antonio
Published: March 2021

Nitrogen-use efficiency (NUE) is a complex trait of great interest in breeding programs because through its improvement, high crop yields can be maintained whilst N supply is reduced. In this study, we report a transcriptomic analysis of four NUE-contrasting eggplant (Solanum melongena) genotypes following short- and long-term exposure to low N, to identify key genes related to NUE in the roots and shoots. The differentially expressed genes in the high-NUE genotypes are involved in the light-harvesting complex and receptor, a ferredoxin–NADP reductase, a catalase and WRKY33. These genes were then used as bait for a co-expression gene network analysis in order to identify genes with the same trends in expression. This showed that up-regulation of WRKY33 triggered higher expression of a cluster of 21 genes and also of other genes, many of which were related to N-metabolism, that were able to improve both nitrogen uptake efficiency and nitrogen utilization efficiency, the two components of NUE. We also conducted an independent de novo experiment to validate the significantly higher expression of WRKY33 and its gene cluster in the high-NUE genotypes. Finally, examination of an Arabidopsis transgenic 35S::AtWRKY33 overexpression line showed that it had a bigger root system and was more efficient at taking up N from the soil, confirming the pivotal role of WRKY33 for NUE improvement.
Painting international law as universal: imperialism and the co-opting of image and art
Authors: Miles Kate
Published: March 2021

Visual international law tells stories. Image and art supporting imperialism in the eighteenth and nineteenth centuries also projected the authority and universalism of international law. This article argues that depictions of treaty-making, of international legal theorists, and of conferences were about painting European international law as ‘successful’—telling stories of an authoritative, universal, and virtue-laden mode of international regulation.
Leadership Lessons for a New Battalion Surgeon
Authors: Maciuba Joseph M , Griffith Matthew E
Published: March 2021

Military medical corps officers often do not have experience with line units until after residency. This case demonstrates the importance of understanding the flow of information within an operational setting. The case also highlights the challenges of advocating for patients as a young officer and physician.
Characteristics of Opioid Prescriptions to Veterans With Chronic Gastrointestinal Symptoms and Disorders Dually Enrolled in the Department of Veterans Affairs and Medicare Part D
Authors: Balbale Salva N , Cao Lishan , Trivedi Itishree , Stulberg Jonah J , Suda Katie J , Gellad Walid F , Evans Charlesnika T , Lambert Bruce L , Keefer Laurie A , Jordan Neil
Published: March 2021

Introduction

Gastrointestinal (GI) symptoms and disorders affect an increasingly large group of veterans. Opioid use may be rising in this population, but this is concerning from a patient safety perspective, given the risk of dependence and lack of evidence supporting opioid use to manage chronic pain. We examined the characteristics of opioid prescriptions and factors associated with chronic opioid use among chronic GI patients dually enrolled in the DVA and Medicare Part D.

Materials and Methods

In this retrospective cohort study, we used linked, national patient-level data (from April 1, 2011, to December 31, 2014) from the VA and Centers for Medicare & Medicaid Services to identify chronic GI patients and observe opioid use. Veterans who had a chronic GI symptom or disorder were dually enrolled in VA and Part D and received ≥1 opioid prescription dispensed through the VA, Part D, or both. Chronic GI symptoms and disorders included chronic abdominal pain, chronic pancreatitis, inflammatory bowel diseases, and functional GI disorders. Key outcome measures were outpatient opioid prescription dispensing overall and chronic opioid use, defined as ≥90 consecutive days of opioid receipt over 12 months. We described patient characteristics and opioid use measures using descriptive statistics. Using multiple logistic regression modeling, we generated adjusted odds ratios and 95% CIs to determine variables independently associated with chronic opioid use. The final model included variables outlined in the literature and our conceptual framework.

Results

We identified 141,805 veterans who had a chronic GI symptom or disorder, were dually enrolled in VA and Part D, and received ≥1 opioid prescription dispensed from the VA, Part D, or both. Twenty-six percent received opioids from the VA only, 69% received opioids from Medicare Part D only, and 5% were “dual users,” receiving opioids through both VA and Part D. Compared to veterans who received opioids from the VA or Part D only, dual users had a greater likelihood of potentially unsafe opioid use outcomes, including greater number of days on opioids, higher daily doses, and higher odds of chronic use.

Conclusions

Chronic GI patients in the VA may be frequent users of opioids and may have a unique set of risk factors for unsafe opioid use. Careful monitoring of opioid use among chronic GI patients may help to begin risk stratifying this group. and develop tailored approaches to minimize chronic use. The findings underscore potential nuances within the opioid epidemic and suggest that components of the VA’s Opioid Safety Initiative may need to be adapted around veterans at a higher risk of opioid-related adverse events.
Applying clock comparison methods to pulsar timing observations
Authors: Chen Siyuan , Vernotte François , Rubiola Enrico
Published: March 2021

Frequency metrology outperforms any other branch of metrology in accuracy (parts in 10−16) and small fluctuations (<10−17). In turn, among celestial bodies, the rotation speed of millisecond pulsars is by far the most stable (<10−18). Therefore, the precise measurement of the time of arrival (TOA) of pulsar signals is expected to disclose information about cosmological phenomena, and to enlarge our astrophysical knowledge. Related to this topic, Pulsar Timing Array projects have been developed and operated for the last decades. The TOAs from a pulsar can be affected by local emission and environmental effects, in the direction of the propagation through the interstellar medium or universally by gravitational waves from super massive black hole binaries. These effects (signals) can manifest as a low-frequency fluctuation over time, phenomenologically similar to a red noise, while the remaining pulsar intrinsic and instrumental background (noise) are white. This article focuses on the frequency metrology of pulsars. From our standpoint, the pulsar is an accurate clock, to be measured simultaneously with several telescopes in order to reject the uncorrelated white noise. We apply the modern statistical methods of time-and-frequency metrology to simulated pulsar data, and we show the detection limit of the correlated red noise signal between telescopes.
On the absence of backsplash analogues to NGC 3109 in the ΛCDM framework
Authors: Banik Indranil , Haslbauer Moritz , Pawlowski Marcel S , Famaey Benoit , Kroupa Pavel
Published: March 2021

The dwarf galaxy NGC 3109 is receding 105 km s−1 faster than expected in a Lambda cold dark matter (ΛCDM) timing argument analysis of the Local Group and external galaxy groups within 8 Mpc. If this few-body model accurately represents long-range interactions in ΛCDM, this high velocity suggests that NGC 3109 is a backsplash galaxy that was once within the virial radius of the Milky Way and was slingshot out of it. Here, we use the Illustris TNG300 cosmological hydrodynamical simulation and its merger tree to identify backsplash galaxies. We find that backsplashers as massive (≥4.0 × 1010 M⊙) and distant (≥1.2 Mpc) as NGC 3109 are extremely rare, with none having also gained energy during the interaction with their previous host. This is likely due to dynamical friction. Since we identified 13 225 host galaxies similar to the Milky Way or M31, we conclude that postulating NGC 3109 to be a backsplash galaxy causes >3.96σ tension with the expected distribution of backsplashers in ΛCDM. We show that the dark matter only version of TNG300 yields much the same result, demonstrating its robustness to how the baryonic physics is modelled. If instead NGC 3109 is not a backsplasher, consistency with ΛCDM would require the 3D timing argument analysis to be off by 105 km s−1 for this rather isolated dwarf, which we argue is unlikely. We discuss a possible alternative scenario for NGC 3109 and the Local Group satellite planes in the context of MOND, where the Milky Way and M31 had a past close flyby 7–10 Gyr ago.
Mapping Global Neurosurgery Research Collaboratives: A Social Network Analysis of the 50 Most Cited Global Neurosurgery Articles
Authors: Kanmounye Ulrick Sidney , Sebopelo Lorraine Arabang , Keke Chiuyu , Zolo Yvan , Senyuy Wah Praise , Endalle Genevieve , Takoukam Régis , Sichimba Dawin , Nguembu Stéphane , Ghomsi Nathalie
Published: March 2021

Social network analysis of bibliometric data evaluates the relationships between the articles, authors, and themes of a research niche. The network can be visualized as maps composed of nodes and links. This study aimed to identify and evaluate the relationships between articles, authors, and keywords in global neurosurgery. The authors searched global neurosurgery articles on the Web of Science database from inception to June 18, 2020. The 50 most cited articles were selected and their metadata (document coupling, co-authorship, and co-occurrence) was exported. The metadata were analyzed and visualized with VOSViewer (Centre for Science and Technology Studies, Leiden University, The Netherlands). The articles were published between 1995 and 2020 and they had a median of 4.0 (interquartile range [IQR] = 5.0) citations. There were 5 clusters in the document coupling and 10 clusters in the co-authorship analysis. A total of 229 authors contributed to the articles and Kee B. Park contributed the most to articles (14 publications). Backward citation analysis was organized into 4 clusters and co-occurrence analysis into 7 clusters. The most common themes were pediatric neurosurgery, neurotrauma, and health system strengthening. The authors identified trends, contributors, and themes of highly cited global neurosurgery research. These findings can help establish collaborations and set the agenda in global neurosurgery research.
Falls and Fear of Falling in Shunted Idiopathic Normal Pressure Hydrocephalus—The Idiopathic Normal Pressure Hydrocephalus Comorbidity and Risk Factors Associated With Hydrocephalus Study
Authors: Larsson Jenny , Israelsson Hanna , Eklund Anders , Lundin-Olsson Lillemor , Malm Jan
Published: March 2021

BACKGROUND

Gait and balance impairment are typical symptoms of idiopathic normal pressure hydrocephalus (INPH), implicating that falls may afflict these patients.

OBJECTIVE

To investigate falls, related injuries, and associated psychological features, before and after shunt surgery for INPH and compared to the general population.

METHODS

The study included 176 patients shunted for INPH and 368 age- and sex-matched controls. Falls, fear of falling (FOF), fall-related injuries (mild-severe), confidence in avoiding falls (Swedish Falls Efficacy Scale (FES(S)), quality of life (QoL; EuroQoL 5-dimension 5 level instrument), and symptoms of depression (Geriatric Depression Scale 15) were investigated. Pre- and postoperative observational times were 12 mo before surgery and 21 mo after (mean). Recurrent fallers fell ≥2 times.

RESULTS

More INPH patients than controls were recurrent fallers (67% vs 11%; P < .001). They feared falling more often (FOF, mean ± standard deviation: 3.3 ± 1.1 vs 1.6 ± 0.9; P < .001) and had lower confidence in avoiding falls (FES(S) 78 ± 40 vs 126 ± 14; P < .001). After surgery, INPH patients improved in all parameters but they did not reach the levels of the controls. Among fallers there was no difference between patients and controls in the severity of injuries suffered. Low QoL and symptoms of depression were more common among recurrent fallers than one-time or nonfallers in both shunted patients and controls (P ≤ .001).

CONCLUSION

Falls, FOF, and low confidence in avoiding falls are considerable problems in INPH that may be reduced by shunt surgery. We suggest that remaining risk of falling and preventative measures are routinely considered in postoperative follow-ups and rehabilitation planning.
A systematic review of the utility of amino acid PET in assessing treatment response to bevacizumab in recurrent high-grade glioma
Authors: Hughes Kendall L , O’Neal Christen M , Andrews Bethany J , Westrup Alison M , Battiste James D , Glenn Chad A
Published: March 2021

Background. Currently, bevacizumab (BEV), an antiangiogenic agent, is used as an adjunctive therapy to re-irradiation and surgery in patients with recurrent high-grade gliomas (rHGG). BEV has shown to decrease enhancement on MRI, but it is often unclear if these changes are due to tumor response to BEV or treatment-induced changes in the blood brain barrier. Preliminary studies show that amino acid PET can aid in distinguishing these changes on MRI.

Methods. The authors performed a systematic review of PubMed and Embase through July 2020 with the search terms ‘bevacizumab’ or ‘Avastin’ and ‘recurrent glioma’ and ‘PET,’ yielding 38 papers, with 14 meeting inclusion criteria.

Results. Thirteen out of fourteen studies included in this review used static PET and three studies used dynamic PET to evaluate the use of BEV in rHGG. Six studies used the amino acid tracer [18F]FET, four studies used [11C]MET, and four studies used [18F]FDOPA.

Conclusion. [18F]FET, [11C]MET, and [18F]FDOPA PET in combination with MRI have shown promising results for improving accuracy in diagnosing tumor recurrence, detecting early treatment failure, and distinguishing between tumor progression and treatment-induced changes in patients with rHGG treated with BEV.
A Genome-Wide Association Study of Nausea Incidence in Varenicline-Treated Cigarette Smokers
Authors: Chenoweth Meghan J , Lerman Caryn , Knight Jo , Tyndale Rachel F
Published: March 2021

Introduction

Varenicline is the most efficacious smoking cessation treatment; however, long-term cessation rates tend to be <25%. Nausea, the most common side effect of varenicline, observed in ~28% of individuals treated, peaks early following treatment initiation and reduces cessation success. Genetic variation influences treatment response, however genetic contributors to individual differences in side effects are less understood.

Methods

We conducted a genome-wide association study of nausea incidence at 1 week following the initiation of varenicline treatment (corresponding to the target quit date) in 189 cigarette smokers of European ancestry (NCT01314001). Additive genetic models examining the likelihood of experiencing any versus no nausea controlled for population substructure, age, and sex. Variants with minor allele frequencies (MAF)≥10% were considered.

Results

Fifty-seven (30.2%) out of 189 participants reported nausea. The top variant associated with nausea was rs1568209 (odds ratio [OR] = 2.61 for A vs. G allele; 95% confidence interval [CI] = 1.65,4.15; p = 2.1e-7; MAF = 48.7%), mapping to the SLCO3A1 drug transporter gene on chromosome 15. In the same trial, rs1568209 was not associated with nausea in either the nicotine patch (p = .56; n = 181) or placebo (p = .59; n = 174) arms. In varenicline-treated smokers, the incidence of nausea was higher in females (44.6%; n = 74) versus males (20.9%; n = 115) (p = .001), however there was no evidence of a difference in the influence of rs1568209 on nausea between the sexes (p for sex*genotype interaction = .36). Future studies in larger samples are required to test the robustness of this finding.

Conclusions

Variation in SLCO3A1 may influence the risk for developing nausea in varenicline-treated smokers, which may alter adherence and cessation.

Implications

Varenicline-associated nausea reduces adherence and limits cessation success. Previous candidate gene association studies showed genetic factors influence nausea on varenicline. This pilot genome-wide investigation of nausea, the most common side effect associated with varenicline treatment and an important cause of treatment discontinuation, suggests the potential involvement of common variation in the SLCO3A1 drug transporter gene.