bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized Trial of Two Induction Therapy Regimens for High-Risk Neuroblastoma: HR-NBL1.5 International Society of Pediatric Oncology European Neuroblastoma Group Study
Authors: Garaventa Alberto , Poetschger Ulrike , Valteau-Couanet Dominique , Luksch Roberto , Castel Victoria , Elliott Martin , Ash Shifra , Chan Godfrey C. F. , Laureys Geneviève , Beck-Popovic Maja , Vettenranta Kim , Balwierz Walentyna , Schroeder Henrik , Owens Cormac , Cesen Maja , Papadakis Vassilios , Trahair Toby , Schleiermacher Gudrun , Ambros Peter , Sorrentino Stefania , Pearson Andrew D. J. , Ladenstein Ruth Lydia
Published: June 2021

PURPOSE

Induction therapy is a critical component of the therapy of high-risk neuroblastoma. We aimed to assess if the Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5) would improve metastatic complete response (mCR) rate and 3-year event-free survival (EFS) compared with rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C]).

PATIENTS AND METHODS

Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4/4s aged < 1 year with MYCN amplification were eligible for random assignment to rCOJEC or MSKCC-N5. Random assignment was stratified according to national group and metastatic sites. Following induction, therapy comprised primary tumor resection, high-dose busulfan and melphalan, radiotherapy to the primary tumor site, and isotretinoin with ch14.18/CHO (dinutuximab beta) antibody with or without interleukin-2 immunotherapy. The primary end points were mCR rate and 3-year EFS.

RESULTS

A total of six hundred thirty patients were randomly assigned to receive rCOJEC (n = 313) or MSKCC-N5 (n = 317). Median age at diagnosis was 3.2 years (range, 1 month to 20 years), and 16 were younger than 1 year of age with MYCN amplification. mCR rate following rCOJEC induction (32%, 86/272 evaluable patients) was not significantly different from 35% (99/281) with MSKCC-N5 ( P = .368), and 3-year EFS was 44% ± 3% for rCOJEC compared with 47% ± 3% for MSKCC-N5 ( P = .527). Three-year overall survival was 60% ± 3% for rCOJEC compared with 65% ± 3% for MSKCC-N5 ( P = .379). Toxic death rates with both regimens were 1%. However, nonhematologic CTC grade 3 and 4 toxicities were higher with MSKCC-N5: 68% (193/283) versus 48% (129/268) ( P < .001); infection 35% versus 25% ( P = .011); stomatitis 25% versus 3% ( P < .001); nausea and vomiting 17% versus 7% ( P < .001); and diarrhea 7% versus 3% ( P = .011).

CONCLUSION

No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group.
Text and Document in Dante’s Vita nova
Authors: Del Puppo Dario
Published: June 2021

This article considers the importance of material philological features of the early manuscripts of Dante’s Vita nova for the work’s critical reception. Over the centuries, editors (most notably Giovanni Boccaccio) have recast textual meaning in the work mainly by marginalizing the poet’s glosses and by reformatting the poems. Attention to the material features of the earliest extant manuscript of the Vita nova (MS Martelli 12) with respect to later copies, however, prompts us to consider the creative interplay between Dante’s prosimetrum and the material features of the manuscript. To interpret a text critically is to acknowledge and to examine also how a manuscript or print edition orients textual interpretation. The editorial history of the Vita nova teaches us about the cultural processes and discourses of literary culture and about Italian literary history.
Cultural Mediations and Material Contexts of Dante’sCommedia:The Case of Beinecke MS 428
Authors: Magni Isabella
Published: June 2021

The textual and cultural interpretations related to the material construction of the first manuscript copies of Dante’s Commedia play a crucial role in shaping its transmission and inevitably also the text that we read today. The processes of preparation and the material structures of these codices, in fact, often reflect more the culture in which they were created than the culture of the original work itself. Starting from a reflection about issues of cultural mediations and material contexts of the early diffusion of Dante’s Commedia, this article introduces a new case study: fourteenth-century manuscript Beinecke Library MS 428, a deluxe copy commissioned by the Bini family.
Painting (and Writing) over Dante
Authors: Storey H. Wayne
Published: June 2021

With the advent of studies in the area of mise-en-page and the increased interest in the relationships among text, image, and material structures in medieval manuscripts, the inherent problems of interpretation and “intentionality” have often been concentrated in critics’ assignment of meaning and cultural “readings” to medieval illuminators. Yet numerous sources, especially the instructions to illuminators that remain still visible in unfinished manuscripts, confirm that methods of work in the illustrating of medieval texts were guided by very different criteria than interpretation. Instead, the material and mechanical realities of reproducing medieval texts, among them Dante’s Commedia, were often subject more to production efficiency, cost effectiveness, taste, and scribal and cultural norms. Examining the instructions to the illuminator of an unfinished copy of a uniquely edited Veneto copy of the Commedia, initially produced in the 1340s (Codex Italicus 1 of the University Library and Archives of Eötvös Loránd University in Budapest), this essay investigates the systems and constructions imposed on the Commedia by a new scribal culture in the reproduction and “visual glossing” of the poem.
Molecular models of LINC complex assembly at the nuclear envelope
Authors: Jahed Zeinab , Domkam Nya , Ornowski Jessica , Yerima Ghafar , Mofrad Mohammad R. K.
Published: June 2021

Large protein complexes assemble at the nuclear envelope to transmit mechanical signals between the cytoskeleton and nucleoskeleton. These protein complexes are known as the linkers of the nucleoskeleton and cytoskeleton complexes (LINC complexes) and are formed by the interaction of SUN and KASH domain proteins in the nuclear envelope. Ample evidence suggests that SUN–KASH complexes form higher-order assemblies to withstand and transfer forces across the nuclear envelope. Herein, we present a review of recent studies over the past few years that have shed light on the mechanisms of SUN–KASH interactions, their higher order assembly, and the molecular mechanisms of force transfer across these complexes.
Olga Tokarczuk is in A Dialogue between James W. Underhill and Adam Głaz on Filtering Olga Tokarczuk’s “Tender Worldview” into English during her Nobel Lecture
Authors: Underhill James W. , Głaz Adam
Published: June 2021

In December 2019, Olga Tokarczuk, the Nobel Prize laureate in literature for 2018, delivered the Nobel lecture in her native Polish. It was therefore up to her English translators, Jennifer Croft and Antonia Lloyd-Jones, to relay the laureate’s message to the wider audience. Two linguists and translators, James W. Underhill and Adam Głaz, discuss this Nobel lecture in its broader historical, political, and social context, recognizing Olga Tokarczuk’s position on topical issues, the role she plays in contemporary Poland, as well as the controversies she arouses. But Tokarczuk is predominantly a writer: her lecture is concerned with literature and it is literature. In a masterly fashion, the lauretate champions the creative power of storytelling, explores her notion of the tender narrator, and constructs intriguing analogies. She weaves nuanced semantic networks around the Polish words tęsknić/tęsknota (‘miss/missing’ or ‘long/longing for’) and jestem (‘here I am’). Underhill and Głaz discuss the meanders of the English translation of the lecture, pointing out the challenges that the translators had to face and suggesting alternative ways of coping with them. Through dialogue, they inquire into the nature of translation as an endeavour that is profoundly communicative and interpersonal. They emphasize that Olga Tokarczuk is an important voice; the role of her translators is to make this voice heard worldwide.
Evaluation of Yield Production and Chemical Composition of Three Types of Forage Legumes at Different Cutting Intervals and Cutting Times to Assess Their Benefits as Ruminant Animal Feed
Authors: Rupitak Quanjai , Srisaikham Supreena
Published: June 2021

The purpose of this study was to evaluate the potential of yield production and chemical composition response to cutting intervals of three forage legumes over a 5 month period of the dry season in Sa Kaeo province for use as an alternative forage for farmers. The experiment was conducted in a factorial arrangement in randomized complete block design. The first factor was the types of forage legumes, including alfalfa, hamata and stylo ‘Tha pra’ and the second factor was the cutting intervals at 30, 45, 60 and 75 days. The results for stylo ‘Tha pra’ showed that the average height, total weight per area, fresh weight (FW) and dry weight (DW) per plant were the highest (P <0.001). The cutting interval at 75 days provided the highest average height, FW and DW in all legume forage types. The FW and DW increased with increases in the cutting times (number of cuts) at all cutting intervals for all three forage legume types. The three different types of forage legumes and the different cutting intervals resulted in different chemical compositions (P <0.001) except for dry matter (DM) for which there was only a difference from the cutting interval. Each chemical composition showed an unequal response to the increase in cutting times.

Keywords: Chemical composition, Cutting intervals, Cutting times, Forage legumes, Ruminant feed, Yield production
Hydro- and Osmo-priming Effects on Upland Rice Exposed to Drought Conditions at Vegetative and Reproductive Stages
Authors: Kartika Kartika , Lakitan Benyamin , Purnama Ria Rofiqoh
Published: June 2021

Drought stress during vegetative and/or generative stages could cause massive reduction in rice yield. This study evaluated effectiveness of hydro- and osmo-priming on improving seed germination, growth and development of upland rice under drought stress during late vegetative, booting, or heading stage. Treatments consisted of hydro-priming and osmo-priming consisted of three polyethylene glycol (PEG) concentrations i.e. 10%, 15%, and 20%. Results showed that application of osmo-priming at 10% PEG required longer time (21.93 hours) to reach 50% germination, lower germination and lower vigor index. However, after germination, seeds primed with 10% PEG exhibited better seedling growth than other seed priming treatments. Effects of seed priming on yield components were overshadowed by drought exposures. Drought imposed during vegetative stage did not significantly affect yield; however, regardless of seed priming treatments, yield reduction was inevitable in rice plants exposed to drought during booting or heading stages. Rice plant shortened time to reached physiological maturity as an adaptive mechanism if drought treatment was applied during heading stage.

Keywords: Germination, Polyethylene glycol, Seedling growth, Seed priming, Yield component
Valuation of External Costs of Wet-Season Lowland Rice Production Systems in Northern Thailand
Authors: Thambhitaks Kamthorn , Kitchaicharoen Jirawan
Published: June 2021

This study aims to assess the external costs of environmental impacts associated with the rice production systems using LCA approach and evaluated them into the economic value. The study compared the different chemical and energy use, as well as straw management of the three different rice production systems, included the mainstream conventional rice system, GAP rice system, and the organic rice system in Northern Thailand. The LCA analysis quantified the midpoint and endpoint of five environmental impacts, including climate change, terrestrial acidification, eutrophication, water depletion, and human health damage, from cradle-to-farm gate.

The results of economic valuation revealed that the external costs of the conventional and GAP rice systems have significantly higher than that of the organic system. Most external costs came from the wastewater treatment cost due to the eutrophication mainly arising from the use of chemical fertilizer. Besides, about one-fourth of the total external costs came from the human health damage cost due to the open-air rice straw burning. To reduce the external costs of rice production, the amount of chemical fertilizer use causing eutrophication should be diminished and replaced by applying organic fertilizer from incorporating rice straw into the soil as well as growing a rotational crop after rice cultivation to stop the open-air rice straw burning and reduced the human health damage. The government should encourage rice farmers to the organic rice farming and manage the rice straw without burning because they may have the cost burden, whereas society gains more benefits from less pollution.

Keywords: Economic valuation, Environmental impacts, Life Cycle Assessment, Rice production systems, Thai Good Agricultural Practice
Sterile Tissue Preparation and Callus Induction of Curcuma longa Linn.
Authors: Kaewthip Warunya , Dheeranupattana Srisulak , Junta Pornchai , Shank Lalida
Published: June 2021

Curcuma longa Linn. (family Zingiberaceae), commonly known as ‘turmeric’, is native to Southeast Asia. Turmeric has been used for color, flavor as a spice in cuisine and employed for treatment of various diseases. The major component in yellow-pigmented fraction of turmeric is curcuminoids. Curcuminoid production in callus of C. longa Linn. is our focus of study. Sterile techniques to obtain germ-free of C. longa Linn. explants were investigated and the results showed that immersing rhizome buds in 70% ethanol for 5 min, followed by 0.10% HgCl2 for 10 min offered approximately 66% survival rate. Multiple shoots were generated from the aseptic rhizome explants cultured on Murashige and Skoog (MS) agar medium fortified with 3.00 µM of 6-Benzylaminopurine (BA) and 0.50 µM of 1-Naphthaleneacetic acid (NAA) at 25 ± 2°C under a photoperiod of 16 h light and 8 h dark. The sterile leaf sheath and root were subsequently used for callus induction which produced various responses when cultured on MS agar medium fortified with different concentrations of 2,4-dichlorophenoxy acetic acid (2, 4-D), Thidiazuron (TDZ) and BA. The highest induction yields of friable callus were obtained from leaf sheath segments cultured on MS agar medium fortified with 0.50 mg/l 2, 4-D which are the conditions proposed for successful production of callus culture of C. longa Linn.

Keywords: Callus induction, Curcuma longa Linn., Turmeric, Plant tissue culture
Between Women: Archival and Theoretical Methods in Early Modern Women's Writing
Authors: Shirley Christopher
Published: June 2021

Abstract: This article proposes that combining deep archival inquiry and rigorous theoretical analysis generates one potential methodological future for the field of early modern women's writing. By investigating the manuscript circulation of Katherine Philips's poetry within her close-knit coterie through the lens of queer theory, it demonstrates that this combination can both further deep archival research into women's writing and precipitate the refinement of theoretical models. In particular, it notes that men's interactions with women's writing in Philips's Society, especially, in one case, as the scribe of one of its signal manuscript collections, reveals a consensual form of female homosocial triangulation that is distinct from Eve Kosofsky Sedgwick's model of repressive male homosocial triangulation. In the method the article thus sketches, theory calibrates archival inquiry while the historical details recovered by archival inquiry provoke rearticulation of theoretical models. This dialogical procedure traces one potential path forward for the study of early modern women's writing.
Unconventional Experiments: Teaching Early Modern Women Writers
Authors: Burke Victoria E.
Published: June 2021

Abstract: This article discusses an approach to teaching early modern women's writing that uses book history and formalism as its main tools. It argues that digital editions of the poetry of Mary Wroth, Hester Pulter, and Margaret Cavendish enable new ways to study these works. Paul Salzman's Wroth edition places different versions of the same poem (including digitized images of the holograph manuscript) side by side, which shows how a misreading of her first sonnet occurred. The Pulter Project: Poet in the Making is producing multiple editions of Hester Pulter's 120 poems, plus additional "curations" that bring contextual materials, including poems by male writers, into dialogue with the poems. Close readings of Pulter's poems demonstrate a poet of formal sophistication. Liza Blake's edition of Margaret Cavendish's Poems and Fancies highlights material issues by offering detailed textual notes that compare the three very different printed versions. Her digital edition also suggests pathways for formalist analysis, such as proposing Cavendish as a metaphysical poet, as does the work of Lara Dodds, which suggests we embrace Cavendish's supposed "bad writing." After a brief analysis of Cavendish's generically experimental Sociable Letters , this article turns to a recent example of recovery research in the discovery of Dorothy Calthorpe's manuscripts and ends by suggesting future trends in the field. These include analyzing known works from multiple perspectives and studying a wider range of sources that more accurately reflects early modern conceptions of authorship.
Sugar, Spice, and Cannibalism
Authors: Tigner Amy L.
Published: June 2021

Abstract: Amy L. Tigner on Tasting Difference: Food, Race, and Cultural Encounters in Early Modern Literature by Gitanjali G. Shahani
Performance improvement for compressive light field display based on the depth distribution feature
Authors: Zhu Liming , Lv Guoqiang , Xv Liye , Wang Zi , Feng Qibin
Published: June 2021

Compressive light field (CLF) display using multi-layer spatial light modulators (SLMs) is a promising technique for three-dimensional (3D) display. However, conventional CLF display usually uses the reference plane with fixed depth, which does not consider the relationship between the depth distribution of the object and the image quality. To improve the quality of the reconstructed image, we further analyze the relationship between them in the paper. The theoretical analysis reveals that the object with a closer distance to the physical layer has a better reconstruction quality when the SLM layers have the same pixel density. To minimize the deviation between the reconstructed light field and the original light field, we propose a method based on the depth distribution feature to automatically guide the light field optimization without increasing the layered number or the refresh rate. When applied to a different scene, it could detect the dense region of depth information and map them as close to the physical layers as possible by offsetting the depth of the reference plane. Simulation and optical experiments with the CLF display are demonstrated to verify the proposed method. We implement a CLF display that consists of four-layer stacked display panels and the distance between two adjacent layers is 5cm. When the proposed method is applied, the peak signal-to-noise ratio (PSNR) is improved by 2.4dB in simulations and 1.8dB in experiments.
Photonics-assisted joint radar and communication system based on an optoelectronic oscillator
Authors: Xue Zhujun , Li Shangyuan , Xue Xiaoxiao , Zheng Xiaoping , Zhou Bingkun
Published: June 2021

This paper reports a photonics-assisted joint radar and communication system for intelligent transportation based on an optoelectronic oscillator (OEO). By manipulating the optical multi-dimensional processing module inserted in the OEO loop, two phase-orthogonal integrated signals are generated with low phase noise and high frequency, as the communication data loaded on the overall polarity of radar pulses. At the receiver, single-channel matched filtering and two-channel IQ data fusion are utilized to retrieve the communication data and the range profile, without any performance deterioration of either. In this way, the contradiction between the performance of two functions existing in the previous scheme is solved, and the integrated performance can be further optimized as bandwidth increases. A proof-of-concept experiment with 2 GHz bandwidth at 24 GHz, which is the operating frequency of short-range automotive radar, is carried out to verify that the proposed system can meet the requirement of the intelligent vehicles in the short-range scene. A communication capacity of 335.6 Mbps, a range profile with a resolution of 0.075 m, and a peak-to-sidelobe ratio (PSLR) of 20 dB is demonstrated under the experimental condition. The error vector magnitude (EVM) curve and constellation diagrams versus received power are measured, where the EVM is −8 and −14.5 dB corresponding to a power of −14 and 6 dBm, respectively.
Three-dimensional nanothermometry below the diffraction limit
Authors: Thiem J. , Spelthann S. , Neumann J. , Ruehl A. , Ristau D.
Published: June 2021

Lanthanide-doped nanothermometers are used to measure temperature through changes in their emission characteristic with sensitivities of up to a few %/K. In contrast to their sensitivity, their spatial resolution, which is of critical importance for various applications, has not been thoroughly studied and optimized. We numerically investigated the improvement in spatial resolution of nanothermometers with a stimulated emission depletion microscopy approach. Fundamental relationships between spatial and temperature resolution were identified by using different beam parameters for the excitation and depletion beams. Our simulations predict contactless temperature measurement below the diffraction limit with temperature resolution of

±

1.25

K

. We further studied the influence of sample thickness and position on both temperature and spatial resolution and showed the potential of three-dimensional measurements.
Bivalent chromatin as a therapeutic target in cancer: An in silico predictive approach for combining epigenetic drugs
Authors: Alarcón Tomás , Sardanyés Josep , Guillamon Antoni , Menendez Javier A.
Published: June 2021

Tumour cell heterogeneity is a major barrier for efficient design of targeted anti-cancer therapies. A diverse distribution of phenotypically distinct tumour-cell subpopulations prior to drug treatment predisposes to non-uniform responses, leading to the elimination of sensitive cancer cells whilst leaving resistant subpopulations unharmed. Few strategies have been proposed for quantifying the variability associated to individual cancer-cell heterogeneity and minimizing its undesirable impact on clinical outcomes. Here, we report a computational approach that allows the rational design of combinatorial therapies involving epigenetic drugs against chromatin modifiers. We have formulated a stochastic model of a bivalent transcription factor that allows us to characterise three different qualitative behaviours, namely: bistable, high- and low-gene expression. Comparison between analytical results and experimental data determined that the so-called bistable and high-gene expression behaviours can be identified with undifferentiated and differentiated cell types, respectively. Since undifferentiated cells with an aberrant self-renewing potential might exhibit a cancer/metastasis-initiating phenotype, we analysed the efficiency of combining epigenetic drugs against the background of heterogeneity within the bistable sub-ensemble. Whereas single-targeted approaches mostly failed to circumvent the therapeutic problems represented by tumour heterogeneity, combinatorial strategies fared much better. Specifically, the more successful combinations were predicted to involve modulators of the histone H3K4 and H3K27 demethylases KDM5 and KDM6A/UTX. Those strategies involving the H3K4 and H3K27 methyltransferases MLL2 and EZH2, however, were predicted to be less effective. Our theoretical framework provides a coherent basis for the development of an in silico platform capable of identifying the epigenetic drugs combinations best-suited to therapeutically manage non-uniform responses of heterogenous cancer cell populations.
lra: A long read aligner for sequences and contigs
Authors: Ren Jingwen , Chaisson Mark J. P.
Published: June 2021

It is computationally challenging to detect variation by aligning single-molecule sequencing (SMS) reads, or contigs from SMS assemblies. One approach to efficiently align SMS reads is sparse dynamic programming (SDP), where optimal chains of exact matches are found between the sequence and the genome. While straightforward implementations of SDP penalize gaps with a cost that is a linear function of gap length, biological variation is more accurately represented when gap cost is a concave function of gap length. We have developed a method, lra, that uses SDP with a concave-cost gap penalty, and used lra to align long-read sequences from PacBio and Oxford Nanopore (ONT) instruments as well as de novo assembly contigs. This alignment approach increases sensitivity and specificity for SV discovery, particularly for variants above 1kb and when discovering variation from ONT reads, while having runtime that are comparable (1.05-3.76×) to current methods. When applied to calling variation from de novo assembly contigs, there is a 3.2% increase in Truvari F1 score compared to minimap2+htsbox. lra is available in bioconda (https://anaconda.org/bioconda/lra) and github (https://github.com/ChaissonLab/LRA).
Modeling the impact of single-cell stochasticity and size control on the population growth rate in asymmetrically dividing cells
Authors: Barber Felix , Min Jiseon , Murray Andrew W. , Amir Ariel
Published: June 2021

Microbial populations show striking diversity in cell growth morphology and lifecycle; however, our understanding of how these factors influence the growth rate of cell populations remains limited. We use theory and simulations to predict the impact of asymmetric cell division, cell size regulation and single-cell stochasticity on the population growth rate. Our model predicts that coarse-grained noise in the single-cell growth rate λ decreases the population growth rate, as previously seen for symmetrically dividing cells. However, for a given noise in λ we find that dividing asymmetrically can enhance the population growth rate for cells with strong size control (between a “sizer” and an “adder”). To reconcile this finding with the abundance of symmetrically dividing organisms in nature, we propose that additional constraints on cell growth and division must be present which are not included in our model, and we explore the effects of selected extensions thereof. Further, we find that within our model, epigenetically inherited generation times may arise due to size control in asymmetrically dividing cells, providing a possible explanation for recent experimental observations in budding yeast. Taken together, our findings provide insight into the complex effects generated by non-canonical growth morphologies.
Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice
Authors: Han Wei , Gao Mingxing , Xie Changqing , Zhang Jinhua , Zhao Zikai , Hu Xueying , Zhang Wanpo , Liu Xiaoli , Cao Shengbo , Cheng Guofu , Gu Changqin
Published: June 2021

Japanese encephalitis virus (JEV) is a pathogen that causes severe vector-borne zoonotic diseases, thereby posing a serious threat to human health. Although JEV is potentially neurotropic, its pathogenesis and distribution in the host have not been fully elucidated. In this study, an infected mouse model was established using a highly virulent P3 strain of JEV. Immunohistochemistry and in situ hybridization, combined with anatomical imaging of the mouse brain, were used to dynamically localize the virus and construct three-dimensional (3D) images. Consequently, onset of mild clinical signs occurred in some mice at 3.5 d post JEV infection, while most mice displayed typical neurological signs at 6 d post-infection (dpi). Moreover, brain pathology revealed typical changes associated with non-suppurative encephalitis, which lasted up to 8 d. The earliest detection of viral antigen was achieved at 3 dpi in the thalamus and medulla oblongata. At 6 dpi, the positive viral antigen signals were mainly distributed in the cerebral cortex, olfactory area, basal ganglia, thalamus, and brainstem regions in mice. At 8 dpi, the antigen signals gradually decreased, and the localization of JEV tended to concentrate in the cerebrum and thalamus, while no viral antigen was detected in the brain at 21 dpi. In this model, the viral antigen was first expressed in the reticular thalamic nucleus (Rt), and the virus content is relatively stable. The expression of the viral antigen in the hippocampal CA2 region, the anterior olfactory nucleus, and the deep mesencephalic nucleus was high and persistent. The 3D images showed that viral signals were mostly concentrated in the parietal cortex, occipital lobe, and hippocampus, near the mid-sagittal plane. In the early stages of infection in mice, a large number of viral antigens were detected in denatured and necrotic neurons, suggesting that JEV directly causes neuronal damage. From the time of its entry, JEV is widely distributed in the central nervous system thereby causing extensive damage.
Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host
Authors: Levy David Jessula , Goundry Amy , Laires Raquel S. S. , Costa Tatiana F. R. , Novo Carlos Mendes , Grab Dennis J. , Mottram Jeremy C. , Lima Ana Paula C. A.
Published: June 2021

Trypanosoma brucei rhodesienseis one of the causative agents of Human African Trypanosomiasis (HAT), known as sleeping sickness. The parasite invades the central nervous system and causes severe encephalitis that is fatal if left untreated. We have previously identified ecotin-like inhibitors of serine peptidases, named ISPs, in trypanosomatid parasitic protozoa. Here, we investigated the role of ISP2 in bloodstream formT.b.rhodesiense. We generated gene-deficient mutants lacking ISP2 (Δisp2), which displayed a growth profilein vitrosimilar to that of wild-type (WT) parasites. C57BL/6 mice infected with Δisp2displayed lower blood parasitemia, a delayed hind leg pathological phenotype and survived longer. The immune response was examined at two time-points that corresponded with two peaks of parasitemia. At 4 days, the spleens of Δisp2-infected mice had a greater percentage of NOS2+myeloid cells, IFN-γ+-NK cells and increased TNF-α compared to those infected with WT and parasites re-expressing ISP2 (Δisp2:ISP2). By 13 days the increased NOS2+population was sustained in Δisp2-infected mice, along with increased percentages of monocyte-derived dendritic cells, as well as CD19+B lymphocytes, and CD8+and CD4+T lymphocytes. Taken together, these findings indicate that ISP2 contributes toT.b.rhodesiensevirulence in mice and attenuates the inflammatory response during early infection.
Attitudes and practices of open data, preprinting, and peer-review—A cross sectional study on Croatian scientists
Authors: Baždarić Ksenija , Vrkić Iva , Arh Evgenia , Mavrinac Martina , Gligora Marković Maja , Bilić-Zulle Lidija , Stojanovski Jadranka , Malički Mario
Published: June 2021

Attitudes towards open peer review, open data and use of preprints influence scientists’ engagement with those practices. Yet there is a lack of validated questionnaires that measure these attitudes. The goal of our study was to construct and validate such a questionnaire and use it to assess attitudes of Croatian scientists. We first developed a 21-item questionnaire called Attitudes towards Open data sharing, preprinting, and peer-review (ATOPP), which had a reliable four-factor structure, and measured attitudes towards open data, preprint servers, open peer-review and open peer-review in small scientific communities. We then used the ATOPP to explore attitudes of Croatian scientists (n = 541) towards these topics, and to assess the association of their attitudes with their open science practices and demographic information. Overall, Croatian scientists’ attitudes towards these topics were generally neutral, with a median (Md) score of 3.3 out of max 5 on the scale score. We also found no gender (P = 0.995) or field differences (P = 0.523) in their attitudes. However, attitudes of scientist who previously engaged in open peer-review or preprinting were higher than of scientists that did not (Md 3.5 vs. 3.3, P<0.001, and Md 3.6 vs 3.3, P<0.001, respectively). Further research is needed to determine optimal ways of increasing scientists’ attitudes and their open science practices.
Differential effects of acute cerebellectomy on cough in spontaneously breathing cats
Authors: Musselwhite M. Nicholas , Shen Tabitha Y. , Rose Melanie J. , Iceman Kimberly E. , Poliacek Ivan , Pitts Teresa , Bolser Donald C.
Published: June 2021

The role of the cerebellum in controlling the cough motor pattern is not well understood. We hypothesized that cerebellectomy would disinhibit motor drive to respiratory muscles during cough. Cough was induced by mechanical stimulation of the tracheobronchial airways in anesthetized, spontaneously breathing adult cats (8 male, 1 female), and electromyograms (EMGs) were recorded from upper airway, chest wall, and abdominal respiratory muscles. Cough trials were performed before and at two time points after total cerebellectomy (10 minutes and >1 hour). Unlike a prior report in paralyzed, decerebrated, and artificially ventilated animals, we observed that cerebellectomy had no effect on cough frequency. After cerebellectomy, thoracic inspiratory muscle EMG magnitudes increased during cough (diaphragm EMG increased by 14% at 10 minutes,p= 0.04; parasternal by 34% at 10 minutes and by 32% at >1 hour,p= 0.001 and 0.03 respectively). During cough at 10 minutes after cerebellectomy, inspiratory esophageal pressure was increased by 44% (p= 0.004), thyroarytenoid (laryngeal adductor) muscle EMG amplitude increased 13% (p= 0.04), and no change was observed in the posterior cricoarytenoid (laryngeal abductor) EMG. Cough phase durations did not change. Blood pressure and heart rate were reduced after cerebellectomy, and respiratory rate also decreased due to an increase in duration of the expiratory phase of breathing. Changes in cough-related EMG magnitudes of respiratory muscles suggest that the cerebellum exerts inhibitory control of cough motor drive, but not cough number or phase timing in response to mechanical stimuli in this model early after cerebellectomy. However, results varied widely at >1 hour after cerebellectomy, with some animals exhibiting enhancement or suppression of one or more components of the cough motor behavior. These results suggest that, while the cerebellum and behavior-related sensory feedback regulate cough, it may be difficult to predict the nature of the modulation based on total cerebellectomy.
Allele and haplotype frequencies of human leukocyte antigen-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 by next generation sequencing-based typing in Koreans in South Korea
Authors: Baek In-Cheol , Choi Eun-Jeong , Shin Dong-Hwan , Kim Hyoung-Jae , Choi Haeyoun , Kim Tai-Gyu
Published: June 2021

Allele frequencies and haplotype frequencies of HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 have been rarely reported in South Koreans using unambiguous, phase-resolved next generation DNA sequencing. In this study, HLA typing of 11 loci in 173 healthy South Koreans were performed using next generation DNA sequencing with long-range PCR, TruSight®HLA v2 kit, Illumina MiSeqDx platform system, and Assign™for TruSight™HLA software. Haplotype frequencies were calculated using the PyPop software. Direct counting methods were used to investigate the association with DRB1 for samples with only one copy of a particular secondary DRB locus. We compared these allele types with the ambiguous allele combinations of the IPD-IMGT/HLA database. We identified 20, 40, 26, 31, 19, 16, 4, and 16 alleles of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, respectively. The number of HLA-DRB3/4/5 alleles was 4, 5, and 3, respectively. The haplotype frequencies of most common haplotypes were as follows: A*33:03:01-B*44:03:01-C*14:03-DRB1*13:02:01-DQB1*06:04:01-DPB1*04:01:01 (2.89%), A*33:03:01-B*44:03:01-C*14:03 (4.91%), DRB1*08:03:02-DQA1*01:03:01-DQB1*06:01:01-DPA1*02:02:02-DPB1*05:01:01 (5.41%), DRB1*04:05:01-DRB4*01:03:01 (12.72%), DQA1*01:03:01-DQB1*06:01:01 (13.01%), and DPA1*02:02:02-DPB1*05:01:01 (30.83%). In samples with only one copy of a specific secondary DRB locus, we examined its association with DRB1. We, thus, resolved 10 allele ambiguities in HLA-B, -C (each exon 2+3), -DRB1, -DQB1, -DQA1, and -DPB1 (each exon 2) of the IPD-IMGT/HLA database. Korean population was geographically close to Japanese and Han Chinese populations in the genetic distances by multidimensional scaling (MDS) plots. The information obtained by HLA typing of the 11 extended loci by next generation sequencing may be useful for more exact diagnostic tests on various transplantations and the genetic population relationship studies in South Koreans.
FRAILTY AND DRUG USE
Authors: PALMER K. , MARENGONI A. , RUSSO P. , MAMMARELLA F. , ONDER G.
Published: June 2021

Older adults often have co-occurring multiple chronic and acute diseases, which progressively and steadily increase in prevalence with age (1, 2). The treatment of these diseases usually requires multiple drugs (polypharmacy); it has been estimated that more than 50% of persons aged 65 years or older receive five or more drugs concomitantly (3, 4). Drug use in the older population might raise several concerns related to an increased risk of drug-drug and drug-disease interactions, poor adherence to treatment, and increased risk of adverse drug reactions (5-7). In this chapter we will discuss what role drugs and polypharmacy play in the development, management and treatment of frailty.
MEASURING THE EFFECT OF CARERS ON PATIENTS’ RISK OF ADVERSE HEALTHCARE OUTCOMES USING THE CAREGIVER NETWORK SCORE
Authors: O’CAOIMH R. , CORNALLY N. , SVENDROVSKI A. , WEATHERS E. , FITZGERALD C. , HEALY E. , O’CONNELL E. , O’KEEFFE G. , O’HERLIHY E. , GAO Y. , O’DONNELL R. , O’SULLIVAN R. , LEAHY-WARREN P. , ORFILA F. , PAÚL C. , CLARNETTE R. , MOLLOY D.W.
Published: June 2021

Background: Although caregivers are important in the management of frail, community-dwelling older adults, the influence of different caregiver network types on the risk of adverse healthcare outcomes is unknown. Objective: To examine the association between caregiver type and the caregiver network subtest of The Risk Instrument for Screening in the Community (RISC), a five point Likert scale scored from one (“can manage”) to five (“absent/liability”). To measure the association between caregiver network scores and the one-year incidence of institutionalisation, hospitalisation and death. Design: Observational cohort study. Setting and Participants: Community-dwelling adults, aged >65,attending health centres in Ireland,(n=779). Procedure and Measurements: The caregiver network subtest of the RISC was scored by public health nurses. Caregivers were grouped dichotomously into low-risk (score of one) or high-risk (scores two-five). Results: The majority of patients had a primary caregiver (582/779;75%), most often their child (200/582;34%). Caregiver network scores were highest, indicating greatest risk, when patients had no recognised primary caregiver and lowest when only a spouse or child was available. Despite this, patients with a caregiver were significantly more likely to be institutionalised than those where none was required or identified (11.5% versus 6.5%,p=0.047). The highest one-year incidence of adverse outcomes occurred when state provided care was the sole support; the lowest when private care was the sole support. Significantly more patients whose caregiver networks were scored high-risk required institutionalisation than low-risk networks; this association was strongest for perceived difficulty managing medical domain issues, odds ratio (OR) 3.87:(2.22-6.76). Only perceived difficulty managing ADL was significantly associated with death, OR 1.72:(1.06-2.79). There was no association between caregiver network scores and risk of hospitalisation. Conclusion: This study operationalizes a simple method to evaluate caregiver networks. Networks consisting of close family (spouse/children) and those reflecting greater socioeconomic privilege (private supports) were associated with lower incidence of adverse outcomes. Caregiver network scores better predicted institutionalisation than hospitalisation or death.
SYSTEMATIC LITERATURE REVIEW ON THE RELATIONSHIP BETWEEN BIOMARKERS OF SARCOPENIA AND QUALITY OF LIFE IN OLDER PEOPLE
Authors: WOO T. , YU S. , VISVANATHAN R.
Published: June 2021

Sarcopenia is a multi-faceted geriatric syndrome that is prevalent in the older population. It is an independent risk factor for a variety of devastating health outcomes that threaten the independence of older people. Quality of life is also very important to older people. The objective of this systematic review therefore was to determine the relationship between the biomarkers of sarcopenia (or sarcopenia) and health related quality of life in older people. Systematic searches were done using the electronic databases from MEDLINE and EMBASE. Search terms included sarcopenia, biomarkers of sarcopenia (e.g. muscle mass, grip strength, muscle performance), and health related quality of life. A total of 20 studies were finally included in this review. Only four studies were deemed of good quality. Sarcopenia was associated with poor health related quality of life in both genders from the one cross sectional study defining sarcopenia as per consensus definition. One high quality longitudinal study demonstrated that better physical performance and muscle strength was associated with a slower rate of decline in health related quality of life over six years. Muscle performance and strength were associated with health related quality of life but muscle mass was not in cross-sectional studies. Good quality and longitudinal studies where sarcopenia is defined as per consensus guidelines are required if the impact of the disease on quality of life is to be clarified.
Some hardy type inequalities with finsler norms
Authors: Duy Nguyen Tuan
Published: June 2021

We establish several versions of the subcritical and critical Hardy type inequalities with Bessel pairs on the Euclidean space endowed with a Finsler norm.
L-fuzzy cosets in universal algebras
Authors: Addis Gezahagne Mulat
Published: June 2021

In this paper, we introduce the notion of fuzzy costs in a more general context, in universal algebra by the use of coset terms. We study the structure of fuzzy cosets by applying the general theory of algebraic fuzzy systems. Fuzzy cosets generated by a fuzzy set are characterized in different ways. It is also proved that the class of fuzzy cosets determined by an element forms an algebraic closure fuzzy set system. Finally, we give a set of necessary and sufficient conditions for a given variety of algebras to be congruence permutable by applying the theory of fuzzy cosets.
Jordan amenability of banach algebras
Authors: Valaei Mohammad , Zivari-Kazempour Abbas , Bodaghi Abasalt
Published: June 2021

In this paper, we introduce and study the concepts of Jordan amenability and Jordan biflatness of Banach algebras and compare those with the classical notions of amenability and biflatness. We also find some relations between Jordan amenability and the existence of Jordan approximate and virtual diagonals. These could be considered as Jordan versions of the classical results due to Johnson and Helemskii. We show that, for allC*-algebras, the concepts of amenability and Jordan amenability coincide.
Osmišljavanje smrti i strah od smrti iliti COVID, smrt i baba
Authors: Delić Lidija
Published: June 2021

Na temelju strategija osmišljavanja smrti i bolesti u usmenom folkloru analiziraju se aktuelni narativi o bolesti COVID-19 na internet stranicama i u dnevnoj štampi. Folklorni model sveta kao celovit i konzistentan sistem nema “lakune” kada su u pitanju uzrok, smisao i svrha događanja. Stoga se teške bolesti i iznenadne smrti (smrti koje nisu posledica izbora, epskog podviga, “prirodne” starosti i sl.) sagledavaju kao sustizanje kletve, teškog ogrešenja, predačkog greha i sl. Ista strategija odlikuje, međutim, i dela pop kulture, što govori o fundamentalnoj ljudskoj potrebi da smrt “objasni”. Pažnju nam je privukla činjenica da su se u vestima o smrtima od bolesti COVID-19 permanentno davale informacije o tome da su pacijenti bili stari, sa dijabetesom, onkološki ili dijalizni bolesnici, gojazni i sl., zato što se na taj način od neutralne informacije o smrti išlo ka informaciji koja kreira koncept “zaštićene” većine. Strah od smrti oslonio se u konkretnom slučaju na diskriminatorski koncept Drugog, što istovremeno govori i o alterniranju koncepata drugosti u folkloru i urbanom narativu (greh vs. bolest/starost).
Wix Web-Based Dance Learning Media to Support Teaching in The Pandemic Era in High School
Authors: Sekarningsih Frahma , Budiman Agus , Gustiaji Gaung Rizki
Published: June 2021

This study intends to develop and design a web for dance learning for high school students. This design-based research focuses on two problems, namely (1) the concept of a dance website design which is expected to be suitable for use as a medium for learning dance in the current pandemic era, and (2) the effectiveness of the dance website that is developed as a digital literacy source that can be used as a medium for learning dance in senior high schools. The research method used in this research is design-based research (DBR) with research stages that include design process, design development, evaluation, and design revision. Data collection techniques were carried out by interview and document study. Data analysis was carried out by combining qualitative and quantitative methods. The results show that the website design developed is relevant to the needs and online-based student learning methods needed during the current Covid-19 pandemic. After going through the validation and testing process, the website design developed can be applied properly. The website developed is easily accessible by students and teachers to support the implementation of dance learning that takes place online. Access mechanisms, material structure, content, and existing supporting features can be used as a means of technology literacy education for students.