bluuebunny/crossref_metadata_2025 huggingface dataset:
Large eddy simulations of high-magnetic Reynolds number magnetohydrodynamic turbulence for non-helical and helical initial conditions: A study of two sub-grid scale models
Authors: Jadhav Kiran , Chandy Abhilash J.
Published: August 2021

Pseudo-spectral large eddy simulation (LES) calculations of high-magnetic Reynolds number (Rem) incompressible magnetohydrodynamic (MHD) turbulence are carried out for two initial conditions, namely, the non-helical Orszag–Tang vortex and the strongly helical Arnold–Beltrami–Childress (ABC) flows using two eddy-viscosity-based sub-grid scale (SGS) approaches: the cross-helicity (CH) and dynamic Smagorinsky (DS) models. Validation is conducted through comparisons of 1923 LES calculations with in-house 5123 direct numerical simulations (DNS) at Reynolds number, Re=Rem=800. The results show that the CH model performs better than the DS model. The performance of the SGS models at higher Re is further evaluated by carrying out 3843 LES calculations at Re=Rem=7500. Various quantities including turbulent kinetic energy, turbulent magnetic energy, cross-helicity, helicity, vorticity structures, cosine of angle between velocity and magnetic field, cosine of angle between velocity and vorticity field, kinetic and magnetic energy spectra, and energy fluxes are analyzed to understand the capability of the two LES models in predicting the evolution of MHD turbulence. The higher Reynolds number flow shows a delay in the maximum dissipation with increased transfer of energy toward small scales, resulting in a −5/3 Kolmogorov inertial sub-range scaling. In addition, the effect of Reynolds number on the alignment between velocity and magnetic field, and the energy transfer between kinetic and magnetic energy, is studied. With the ABC flow having strong helicity and zero cross-helicity at low and high Reynolds numbers, a strong dynamo effect is also observed using the LES models, which is consistent with previous DNS.
Environmental factors and predator abundance predict the distribution and occurrence of two sympatric urchin species at Ningaloo Reef, Western Australia
Authors: Westlake Emma L. , Bessey Cindy , Fisher Rebecca , Thomson Damian P. , Haywood Michael D. E.
Published: August 2021

Sea urchins can play a critical ecological role in the functioning of marine benthic ecosystems, mediating competitive interactions between corals and algae. Yet, little is known about factors affecting urchin distribution in intact coral reef systems. This study aims to determine the spatial distribution of two sympatric urchin species, Echinometra mathaei and Echinostrephus molaris, and potential factors contributing to this, within the intact coral reef system of Ningaloo Marine Park, north-western Western Australia. Benthic photographs and surveys were conducted on SCUBA at 126 sites across the Park to determine urchin presence, rugosity, substrate cover, water velocity, and fish predation for each site. Generalised additive models found that E. mathaei presence was positively related to algal cover, rugosity and non-sanctuary zones, suggesting that distribution may be driven by foraging behaviour, habitat complexity and predation. Echinostrephus molaris presence was positively related to habitat and region, suggesting its distribution may be largely driven by hydrodynamics, feeding strategy and regional variation. This study highlighted species-habitat associations and the complexities of these in structuring urchin communities. Although occupying similar niches, the predominantly non-overlapping feeding preferences, and morphological and behavioural differences between E. mathaei and E. molaris enable these species to coexist within the intact reef system of Ningaloo Marine Park.
The spatial pattern of agricultural land use in China during the Holocene Megathermal
Authors: Wu J. , Zhu T. , Li C. B. , Zhang C. H. , Adu Benjamin
Published: August 2021

During the Holocene Megathermal, China entered a stage of extensive agricultural farming, although there are few reports on the possible distribution pattern of agricultural land use. The main objective of this paper is to discuss issues related to the spatial pattern of agricultural land use in China during the Holocene Megathermal. According to historic and archaeological information, three widely planted crops (foxtail millet, broom millet and rice) were selected to represent the main crops, and their distribution was assumed to reflect the agricultural land-use pattern at that time. From the perspective of these crops and their required climate conditions and based on proxy-based ancient temperature and precipitation data combined with modern climate data, an average annual accumulated temperature of ≥10°C in the Holocene Megathermal was retrieved and spatially interpolated to capture a picture of land use. Validation was conducted using archaeological data from 141 agricultural heritage sites. The results indicated that in the Holocene Megathermal, agricultural farming activities were widespread in China The northern-most boundary of agricultural land use was north of Daxinganling, and the southern-most boundary extended to Hainan Island. In the region of the Qinghai–Tibet Plateau where climate is currently much colder than during the Holocene Megathermal, the environment for foxtail millet and broom millet was suitable from the eastern segment of the Qilian Mountains to Lhasa. This study provides a reference for exploring the distribution pattern of agricultural land use in the early period of agricultural production in China and provides useful information for agricultural archaeology.
A production-scale evaluation of nutritional monitoring and decision support software for free-ranging cattle in an arid environment
Authors: Brooks (Turner) Rachel J. , Tolleson Douglas R. , Ruyle George B. , Faulkner Dan B.
Published: August 2021

Range cattle in semi-arid regions are commonly limited by lack of nitrogen and other nutrients from grazing low-quality forage, with managers needing to monitor diet quality to address nutrient limitations. Near-infrared spectroscopy of faecal samples (FNIRS) is an accurate method used to determine diet quality in grazing animals. When combined with a nutritional balance software such as the Nutritional Balance Analyser (NUTBAL), FNIRS can monitor nutritional status and estimate weight change. We aimed to test the ability of NUTBAL to predict animal performance as represented by body condition score (BCS) in cattle grazing on a semi-desert rangeland. BCS and faecal samples were collected from a Red Angus herd (n = 82) at the Santa Rita Ranch (June 2016–July 2017). Standing biomass and botanical composition were measured before each grazing period, and relative utilisation was measured following each grazing period. During the midpoint of grazing in each pasture, 30 BCS and a faecal composite of 15 samples were collected. Faecal derived diet quality varied between a maximum of 10.75% crude protein (CP) and 61.25% digestible organic matter (DOM) in early August 2016, to a minimum value of 4.22% CP and 57.68% DOM in January 2017. Three NUTBAL evaluations were conducted to determine the likelihood of accurately predicting animal performance: one with typical user defined inputs; one with improved environment and herd descriptive inputs; and one with these improvements plus the use of metabolisable protein in the model. This third evaluation confirmed the ability of FNIRS:NUTBAL to predict future BCS within 0.5 BCS more than 75% of the time. With this information, cattle managers in semi-arid regions can better address animal performance needs and nutrient deficiencies.
Social mindfulness and prosociality vary across the globe
Authors: Van Doesum Niels J. , Murphy Ryan O. , Gallucci Marcello , Aharonov-Majar Efrat , Athenstaedt Ursula , Au Wing Tung , Bai Liying , Böhm Robert , Bovina Inna , Buchan Nancy R. , Chen Xiao-Ping , Dumont Kitty B. , Engelmann Jan B. , Eriksson Kimmo , Euh Hyun , Fiedler Susann , Friesen Justin , Gächter Simon , Garcia Camilo , González Roberto , Graf Sylvie , Growiec Katarzyna , Guimond Serge , Hřebíčková Martina , Immer-Bernold Elizabeth , Joireman Jeff , Karagonlar Gokhan , Kawakami Kerry , Kiyonari Toko , Kou Yu , Kuhlman D. Michael , Kyrtsis Alexandros-Andreas , Lay Siugmin , Leonardelli Geoffrey J. , Li Norman P. , Li Yang , Maciejovsky Boris , Manesi Zoi , Mashuri Ali , Mok Aurelia , Moser Karin S. , Moták Ladislav , Netedu Adrian , Pammi Chandrasekhar , Platow Michael J. , Raczka-Winkler Karolina , Reinders Folmer Christopher P. , Reyna Cecilia , Romano Angelo , Shalvi Shaul , Simão Cláudia , Stivers Adam W. , Strimling Pontus , Tsirbas Yannis , Utz Sonja , van der Meij Leander , Waldzus Sven , Wang Yiwen , Weber Bernd , Weisel Ori , Wildschut Tim , Winter Fabian , Wu Junhui , Yong Jose C. , Van Lange Paul A. M.
Published: August 2021

Significance

Cooperation is key to well-functioning groups and societies. Rather than addressing high-cost cooperation involving giving money or time and effort, we examine social mindfulness—a form of interpersonal benevolence that requires basic perspective-taking and is aimed at leaving choice for others. Do societies differ in social mindfulness, and if so, does it matter? Here, we find not only considerable variation across 31 nations and regions but also an association between social mindfulness and countries’ performance on environmental protection. We conclude that something as small and concrete as interpersonal benevolence can be entwined with current and future issues of global importance.
The genetic structure of the Turkish population reveals high levels of variation and admixture
Authors: Kars M. Ece , Başak A. Nazlı , Onat O. Emre , Bilguvar Kaya , Choi Jungmin , Itan Yuval , Çağlar Caner , Palvadeau Robin , Casanova Jean-Laurent , Cooper David N. , Stenson Peter D. , Yavuz Alper , Buluş Hakan , Günel Murat , Friedman Jeffrey M. , Özçelik Tayfun
Published: August 2021

Significance

We delineated the fine-scale genetic structure of the Turkish population by using sequencing data of 3,362 unrelated Turkish individuals from different geographical origins and demonstrated the position of Turkey in terms of human migration and genetic drift. The results show that the genetic structure of present-day Anatolia was shaped by historical and modern-day migrations, high levels of admixture, and inbreeding. We observed that modern-day Turkey has close genetic relationships with the neighboring Balkan and Caucasus populations. We generated a Turkish Variome which defines the extent of variation observed in Turkey, listed homozygous loss-of-function variants and clinically relevant variants in the cohort, and generated an imputation panel for future genome-wide association studies.
Phosphoenolpyruvate depletion mediates both growth arrest and drug tolerance of
Mycobacterium tuberculosis
in hypoxia
Authors: Lim Juhyeon , Lee Jae Jin , Lee Sun-Kyung , Kim Seoyong , Eum Seok-Yong , Eoh Hyungjin
Published: August 2021

Significance

Nonreplicating (NR)
Mycobacterium tuberculosis
(Mtb) was thought to be drug tolerant due to its low metabolic activity. However, drug tolerance often gradually increases by exposure to antibiotics, inferring the role of an adaptive strategy. This study established that drug tolerance of NR Mtb is associated with phosphoenolpyruvate (PEP) anabolic down-regulation. PEP is a substrate of multiple pathways needed for replication; in NR Mtb, their functions were abolished due to PEP depletion. Intriguingly, PEP supplementation partly restored drug sensitivity and prevented the emergence of drug resistance (DR). The results expand our knowledge of how NR Mtb remodels its metabolic networks and propose potential Mtb metabolites as a source of therapeutic adjuvants to synthetically kill NR Mtb and prevent development of DR.
Communicating the unknown
Authors: Müller Marcus , Bartsch Sabine , Zinn Jens O.
Published: August 2021

This paper presents an annotation approach to examine uncertainty in British and German newspaper articles on the coronavirus pandemic. We develop a tagset in an interdisciplinary team from corpus linguistics and sociology. After working out a gold standard on a pilot corpus, we apply the annotation to the entire corpus drawing on an “annotation-by-query” approach inCQPWeb, based on uncertainty constructions that have been extracted from the gold standard data. The annotated data are then evaluated and sociologically contextualised. On this basis, we study the development of uncertainty markers in the period under study and compare media discourses in Germany and the UK. Our findings reflect the different courses of the pandemic in Germany and the UK as well as the different political responses, media traditions and cultural concerns: While markers of fear are more important in British discourse, we see a steadily increasing level of disagreement in German discourse. Other forms of uncertainty such as ‘possibility’ or ‘probability’ are similarly frequent in both discourses.
Narrative evaluation in patient feedback
Authors: Brookes Gavin , McEnery Tony , McGlashan Mark , Smith Gillian , Wilkinson Mark
Published: August 2021

This study examines how patients use narratives to evaluate their experiences of healthcare services online. The analysis draws on corpus linguistic techniques, specifically annotation, applyingLabov and Waletzky’s (1967)framework to a sample of online comments about the NHS in England. Narratives are pervasive in this context, being present more than absent in the patients’ comments, but are particularly prominent in comments which evaluate care negatively. Evaluations can be accomplished through all the structural elements of the narrative, including in combination with one another. However, the presence and ordering of these elements does not seem to be influenced by the type of evaluation given (i.e. positive, negative or more neutral). As mediated social practice, the narratives are shaped by the technological affordances and social dynamics of this context, for instance in the placement of particular structural elements and the design of narratives for particular “imagined” audiences.
The early interferon catches the SARS-CoV-2
Authors: Decker Thomas
Published: August 2021

Interferons establish innate antiviral immunity. Two recent papers inJEM by Lopez et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20211211) and Cheemarla et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210583) show that an appropriate supply of antiviral interferon enables epithelial cells of the nasopharyngeal mucosa to inhibit SARS-CoV-2 growth and that interferon-induced mucosal genes serve as biomarkers of infection.
Shell thickness-controlled synthesis of Au@Ag core–shell nanorods structure for contaminants sensing by SERS
Authors: Thi Dang Lan , Le Nguyen Huy , Van Pham Hai , Nguyen Mai Thi Tuyet
Published: August 2021

The accessibility of contaminants detection methods is urgently required for environmental and food safety control. In this report, we developed the Au@Ag core–shell nanorod structures for contaminants sensing by surface-enhanced Raman spectroscopy (SERS). The silver shell thickness and the corresponding plasmon wavelength of Au@Ag core–shell nanorods were tuned by changing the coating time and the silver precursor amount. Moreover, these structures exhibit ultra-sensitive detection ability for Nile blue A dye and Fenobucarb pesticide sensing by SERS. Interestingly, the highest Raman enhancement factor is obtained for the Au@Ag core–shell sample with a minimal silver shell thickness leaded by the optimal enhancement of the electromagnetic field of bimetallic structures. Hence, our report demonstrates that the combination of unique features of two plasmonic metals into core–shell structures promises potential applicability in SERS-based analysis.
Controlling extended criticality via modular connectivity
Authors: Gutjahr Nikita , Hövel Philipp , Viol Aline
Published: August 2021

Criticality has been conjectured as an integral part of neuronal network dynamics. Operating at a critical threshold requires precise parameter tuning and a corresponding mechanism remains an open question. Recent studies have suggested that topological features observed in brain networks give rise to a Griffiths phase, leading to power-law scaling in brain activity dynamics and the operational benefits of criticality in an extended parameter region. Motivated by growing evidence of neural correlates of different states of consciousness, we investigate how topological changes affect the expression of a Griffiths phase. We analyze the activity decay in modular networks using a susceptible-infected-susceptible propagation model and find that we can control the extension of the Griffiths phase by altering intra- and intermodular connectivity. We find that by adjusting system parameters, we can counteract changes in critical behavior and maintain a stable critical region despite changes in network topology. Our results give insight into how structural network properties affect the emergence of a Griffiths phase and how its features are linked to established topological network metrics. We discuss how those findings could contribute to an understanding of the changes in functional brain networks.
Digital transformation of major scientific meetings induced by the COVID-19 pandemic: insights from the ESC 2020 annual congress
Authors: Roffi Marco , Casadei Barbara , Gouillard Christine , Nambatingué Nata , Daval Ghislain , Bardinet Isabel , Priori Silvia G
Published: August 2021

As a consequence of the COVID-19 pandemic, the European Society of Cardiology (ESC) was forced to pivot the scientific programme of the ESC Congress 2021 into a totally new format for online consumption, The Digital Experience. A variety of new suppliers were involved, including experts in TV studio, cloud infrastructure, online platforms, video management, and online analytics. An information technology platform able to support hundreds of thousands simultaneous connections was built and cloud computing technologies were put in place to help scale up and down the resources needed for the high number of users at peak times. The video management system was characterized by multiple layers of security and redundancy and offered the same fluidity, albeit at a different resolution, to all user independently of the performance of their internet connection. The event, free for all users, was an undisputed success, both from a scientific/educational as well as from a digital technology perspective. The number of registrations increased by almost four-fold when compared with the 2019 record-breaking edition in Paris, with a greater proportion of younger and female participants as well as of participants from low- and middle-income countries. No major technical failures were encountered. For the first time in history, attendees from all around the globe had the same real-time access to the world’s most popular cardiovascular conference.
Molecular alterations of low-grade gliomas in young patients: Strategies and platforms for routine evaluation
Authors: Dandapath Iman , Chakraborty Rituparna , Kaur Kavneet , Mahajan Swati , Singh Jyotsna , Sharma Mehar C , Sarkar Chitra , Suri Vaishali
Published: August 2021

In recent years, it has been established that molecular biology of pediatric low-grade gliomas (PLGGs) is entirely distinct from adults. The majority of the circumscribed pediatric gliomas are driven by mitogen-activated protein kinase (MAPK) pathway, which has yielded important diagnostic, prognostic, and therapeutic biomarkers. Further, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT) Steering Committee in their fourth meeting, suggested including a panel of molecular markers for integrated diagnosis in “pediatric-type” diffuse gliomas. However, a designated set of platforms for the evaluation of these alterations has yet not been mentioned for easier implementation in routine molecular diagnostics. Herein, we have reviewed the relevance of analyzing these markers and discussed the strategies and platforms best apposite for clinical laboratories.
Microsurgical Management of a Marginal Sinus Dural Arteriovenous Fistula: 2-Dimensional Operative Video
Authors: Srinivasan Visish M , Catapano Joshua S , Frisoli Fabio A , Mooney Michael A , Lawton Michael T
Published: August 2021

Dural arteriovenous fistulas (DAVFs) are benign but may present with life-threatening hemorrhage or symptoms of venous hypertension (eg, progressive myelopathy).
1-3
DAVFs follow well-described anatomic patterns.
4
The marginal sinus is located between the layers of the dura, circumferentially around the foramen magnum. It communicates with the basal venous plexus of the clivus anteriorly and the occipital sinus posteriorly.
5,6
Arterial supply to the dura in this region that fistulizes into the sinus arises from meningeal branches from the V3 or V4 segments.

 A man in his early 70s presented with chronic neck pain and new onset of left arm and face paresthesias. He had brisk patellar reflexes bilaterally and a marginal sinus DAVF, with numerous dilated veins around the cisterna magna, causing dorsal cervicomedullary compression. Angiography confirmed the diagnosis of DAVF rather than arteriovenous malformation. Endovascular embolization was considered, but surgery was preferable because of poor transarterial access.

 The patient underwent left far lateral craniotomy and C1 laminectomy with exposure of the condylar fossa. The dura was carefully elevated laterally, revealing a network of dilated tortuous veins, with multiple points of fistulous connection within the dura emanating in a large venous varix. Indocyanine green videoangiography showed the aberrant flow dynamics. The fistulous point was occluded with aneurysm clips on the venous side, then cauterized and interrupted. The patient was discharged within 3 d of surgery and had full resolution of symptoms at 6 wk. Angiography confirmed complete obliteration of the DAVF. The patient provided written informed consent for treatment. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Endonasal Free Flap Reconstruction Combined With Draf Frontal Sinusotomy for Complex Cerebrospinal Fluid Leak: A Technical Report & Case Series
Authors: Lee Jake J , Wick Elizabeth H , Chicoine Michael R , Dowling Joshua L , Leuthardt Eric C , Santiago Paul , Pipkorn Patrik
Published: August 2021

BACKGROUND

Frontal sinus cranialization with closure via bifrontal pericranial flaps is the gold standard for separating the nasofrontal recess from the intracranial cavity for posterior table defects. Despite the high success rate, cerebrospinal fluid (CSF) leak may persist and is particularly challenging when vascularized reconstructive options from the bicoronal incision are exhausted.

OBJECTIVE

To assess a novel endonasal technique using an adipofascial radial forearm free flap delivered to the frontal recess through a Draf sinusotomy to repair complex CSF leaks from the frontal sinus.

METHODS

A retrospective review of 3 patients (all male; ages 42, 43, and 69 yr) with persistent CSF leak despite frontal sinus cranialization and repair with bifrontal pericranium was performed. Etiology of injury was traumatic in 2 patients and iatrogenic in 1 patient after anaplastic meningioma treatment. To create space for the flap and repair the nasofrontal ducts, endoscopic Draf III (Case 1, 3) or Draf IIb left frontal sinusotomy (Case 2) was performed. The forearm flap was harvested, passed through a Caldwell-Luc exposure, and placed within the Draf frontal sinustomy. The flap vessels were tunneled to the left neck and anastomosed to the facial vessels by the mandibular notch.

RESULTS

Intraoperatively, the flaps were well-seated and provided a watertight seal. Postoperative hospital courses were uncomplicated. There were no new CSF leaks or flap necrosis at 12, 14, and 16 mo.

CONCLUSION

Endoscopic endonasal free flap reconstruction through a Draf procedure is a novel viable option for persistent CSF leak after failed frontal sinus cranialization.
Acute injury or illness related to the inhalation of vaping aerosols among children and adolescents across Canada: A cross-sectional survey of Canadian paediatricians
Authors: Zutrauen Sarah , Do Minh T , Ghandour Lina , Moore-Hepburn Charlotte , Beno Suzanne , Richmond Sarah A , Chadi Nicholas
Published: August 2021

Background

Vaping prevalence rates have increased among Canadian youth. Evidence suggests that vaping poses signiﬁcant health risks to children and adolescents.

Objectives

The objectives of the study were to investigate epidemiological characteristics of acute injury/illness cases due to the inhalation of vaping aerosols among children and adolescents across Canada and to explore factors contributing to severe cases.

Methods

Data from the 2019 Canadian Paediatric Surveillance Program cross-sectional survey on vaping-related injury/illness were used. Analyses focused on injury/illness cases (n=71) among children and adolescents aged 0 to 17 years who presented to participating paediatricians for a harm related to the inhalation of vaping aerosols. We conducted descriptive analyses and performed logistic regression to explore associations between severe presentations requiring hospitalization or intensive care unit (ICU) admission and selected case characteristics.

Results

Of the 71 reported injury/illness cases related to inhalation of vaping aerosols, 56% of patients were male, and 68% were aged 15 to 17 years. Nicotine vaping was reported in 42% of cases, and cannabis vaping in 24%. Fifty-four per cent presented with respiratory distress, 18% with symptoms of nicotine toxicity, and 41% required hospitalization and/or admission to the ICU. Cases presenting with respiratory distress were more likely to be hospitalized/admitted to the ICU (odds ratio [OR]=5.37, 95% confidence interval [CI]:1.76 to 16.39).

Conclusions

The inhalation of vaping aerosols among children and adolescents may contribute to acute injury/illness. Clear associations between study variables and severe cases could not be established due to a small sample size. Additional research is needed to determine predictors and preventable risk factors of severe vaping-related injuries.
Macrophage‐derived extracellular vesicles regulates USP5‐mediated HDAC2/NRF2 axis to ameliorate inflammatory pain
Authors: Qu Yao , Xu Yunhe , Jiang Yuncheng , Yu Dehai , Jiang Xi , Zhao Ling
Published: August 2021

Emerging research has highlighted the capacity of microRNA‐23a‐3p (miR‐23a‐3p) to alleviate inflammatory pain. However, the molecular mechanism by which miR‐23a‐3p attenuates inflammatory pain is yet to be fully understood. Hence, the current study aimed to elucidate the mechanism by which miR‐23a‐3p influences inflammatory pain. Bioinformatics was initially performed to predict the inflammatory pain related downstream targets of miR‐23a‐3p in macrophage‐derived extracellular vesicles (EVs). An animal inflammatory pain model was established using Complete Freund's Adjuvant (CFA). The miR‐23a‐3p expression was downregulated in the microglia of CFA‐induced mice, after which the inflammatory factors were determined by ELISA. FISH and immunofluorescence were performed to analyze the co‐localization of miR‐23a‐3p and microglia. Interestingly, miR‐23a‐3p was transported to the microglia via M2 macrophage‐EVs, which elevated the mechanical allodynia and the thermal hyperalgesia thresholds in mice model. The miR‐23a‐3p downstream target, USP5, was found to stabilize HDAC2 via deubiquitination to promote its expression while inhibiting the expression of NRF2. Taken together, the key findings of the current study demonstrate that macrophage‐derived EVs containing miR‐23a‐3p regulates the HDAC2/NRF2 axis by decreasing USP5 expression to alleviate inflammatory pain, which may provide novel therapeutic targets for the treatment of inflammatory pain.
The Characteristics and Risk Factors of Very Asymmetric Keratoconus
Authors: Nakao Gen , Koh Shizuka , Inoue Ryota , Maeno Sayo , Maeda Naoyuki , Nishida Kohji
Published: August 2021

Purpose:

To characterize very asymmetric keratoconus (KC) in terms of clinical demographics and risk factors in the Japanese population.

Methods:

We retrospectively reviewed the clinical records of patients with very asymmetric KC attending a university hospital. Patients with very asymmetric KC had defined clinical KC in one eye and normal topography in the fellow eye. All patients completed a questionnaire on potential risk factors (family history of KC, atopy, asthma, allergy, heart disease, sleep apnea, Down syndrome, eye rubbing, prone sleep position, and dominant hand). These data were compared with those of patients with clinical or topographic KC in both eyes. Subgroup analysis of very asymmetric KC eyes were performed based on the KC status: mild and severe.

Results:

We retrospectively investigated 66 patients with very asymmetric KC and 505 patients with KC. Patients reported eye rubbing (53%–56%), allergy (62%–63%), and atopy (28%–29%) in both groups. There was no significant difference in terms of risk factors between the two groups. Approximately half of the 66 patients with very asymmetric KC had KC eyes ipsilateral to the dominant hand. Subgroup analysis of very asymmetric KC showed that atopy and asthma were more frequent in the mild KC group than in the severe KC group. Forty-four of 60 patients (73.3%) were using corneal, rigid, gas-permeable contact lenses (corneal GPs) for the KC eye, of which 30 patients (68.2%) were also using a corneal GP for the fellow eye.

Conclusions:

The patient-reported frequency of eye rubbing, allergy, and atopy were similar between KC and very asymmetric KC. Furthermore, we found no association between hand dominance and KC laterality.
Salivary Hyalinizing Clear Cell Carcinoma: Report of a Genetically Confirmed Pediatric Case and Review of the Literature
Authors: Palsgrove Doreen N. , Wilson Patrick A. , Oliai Bahram R. , Bishop Justin A.
Published: August 2021

Hyalinizing clear cell carcinoma (HCCC) is a rare but well-recognized low-grade salivary gland malignancy. In addition to being a morphologically distinct neoplasm with cords and nests of predominantly clear cells in hyalinized fibrous stroma, it harbors a characteristic EWSR1 gene rearrangement that can be readily exploited as a diagnostic marker to help distinguish it from other salivary gland tumors with overlapping histomorphology. We herein report a pediatric case of salivary HCCC arising in the oral cavity of an 11-year-old girl. The tumor cells contained moderate amounts of eosinophilic to clear cytoplasm and hyperchromatic nuclei. The stroma was notable for a biphasic spatial arrangement alternating between fibrocellular regions and hyalinized basement membrane–like areas immediately adjacent to tumor cell nests. By immunohistochemistry, the tumor was positive for p40 and negative for SOX10, S100 protein, and smooth muscle actin. Fluorescence in situ hybridization was positive for an EWSR1 chromosomal rearrangement. This is the first reported, molecularly confirmed pediatric case of HCCC. It further expands the diagnostic age range of HCCC to include the pediatric population and highlights the potential risk of misdiagnosis.
Extreme precision in rhythmic interaction is enabled by role-optimized sensorimotor coupling: analysis and modelling of West African drum ensemble music
Authors: Jacoby Nori , Polak Rainer , London Justin
Published: August 2021

Human social interactions often involve carefully synchronized behaviours. Musical performance in particular features precise timing and depends on the differentiation and coordination of musical/social roles. Here, we study the influence of musical/social roles, individual musicians and different ensembles on rhythmic synchronization in Malian drum ensemble music, which features synchronization accuracy near the limits of human performance. We analysed 72 recordings of the same piece performed by four trios, in which two drummers in each trio systematically switched roles (lead versus accompaniment). Musical role, rather than individual or group differences, is the main factor influencing synchronization accuracy. Using linear causal modelling, we found a consistent pattern of bi-directional couplings between players, in which the direction and strength of rhythmic adaptation is asymmetrically distributed across musical roles. This differs from notions of musical leadership, which assume that ensemble synchronization relies predominantly on a single dominant personality and/or musical role. We then ran simulations that varied the direction and strength of sensorimotor coupling and found that the coupling pattern used by the Malian musicians affords nearly optimal synchronization. More broadly, our study showcases the importance of ecologically valid and culturally diverse studies of human behaviour.

This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.
Cross-frequency coupling explains the preference for simple ratios in rhythmic behaviour and the relative stability across non-synchronous patterns
Authors: Dotov Dobromir , Trainor Laurel J.
Published: August 2021

Rhythms are important for understanding coordinated behaviours in ecological systems. The repetitive nature of rhythms affords prediction, planning of movements and coordination of processes within and between individuals. A major challenge is to understand complex forms of coordination when they differ from complete synchronization. By expressing phase as ratio of a cycle, we adapted levels of the Farey tree as a metric of complexity mapped to the range between in-phase and anti-phase synchronization. In a bimanual tapping task, this revealed an increase of variability with ratio complexity, a range of hidden and unstable yet measurable modes, and a rank-frequency scaling law across these modes. We use the phase-attractive circle map to propose an interpretation of these findings in terms of hierarchical cross-frequency coupling (CFC). We also consider the tendency for small-integer attractors in the single-hand repeated tapping of three-interval rhythms reported in the literature. The phase-attractive circle map has wider basins of attractions for such ratios. This work motivates the question whether CFC intrinsic to neural dynamics implements low-level priors for timing and coordination and thus becomes involved in phenomena as diverse as attractor states in bimanual coordination and the cross-cultural tendency for musical rhythms to have simple interval ratios.

This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.
The dual benefits of synchronized mating signals in a Japanese treefrog: attracting mates and manipulating predators
Authors: Legett Henry D. , Aihara Ikkyu , Bernal X. E.
Published: August 2021

In dense mating aggregations, such as leks and choruses, acoustic signals produced by competing male conspecifics often overlap in time. When signals overlap at a fine temporal scale the ability of females to discriminate between individual signals is reduced. Yet, despite this cost, males of some species deliberately overlap their signals with those of conspecifics, synchronizing signal production in the chorus. Here, we investigate two hypotheses of synchronized mating signals in a Japanese treefrog (
Buergeria japonica
): (1) increased female attraction to the chorus (the beacon effect hypothesis) and (2) reduced attraction of eavesdropping predators (the eavesdropper avoidance hypothesis). Our results from playback experiments on female frogs and eavesdropping micropredators (midges and mosquitoes) support both hypotheses. Signal transmission and female phonotaxis experiments suggest that away from the chorus, synchronized calls are more attractive to females than unsynchronized calls. At the chorus, however, eavesdroppers are less attracted to calls that closely follow an initial call, while female attraction to individual signals is not affected. Therefore, synchronized signalling likely benefits male
B. japonica
by both increasing attraction of females to the chorus and reducing eavesdropper attacks. These findings highlight how multiple selective pressures likely promoted the evolution and maintenance of this behaviour.

This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.
Genome-based reclassification of Caldicellulosiruptor lactoaceticus and Caldicellulosiruptor kristjanssonii as later heterotypic synonyms of Caldicellulosiruptor acetigenus
Authors: Habib Neeli , Rao Manik Prabhu Narsing , Xiao Min , Jan Sohail Ahmad , Li Wen-Jun
Published: August 2021

The present study was carried out to re-clarify the taxonomic relationship of

Caldicellulosiruptor acetigenus

,

Caldicellulosiruptor lactoaceticus

and

Caldicellulosiruptor kristjanssonii

. The 16S rRNA sequence similarities between these species of the genus

Caldicellulosiruptor

were above the threshold values (98.65%) for bacterial species delineation. Similarly, the digital DNA–DNA hybridization and average nucleotide and amino acid identity values were greater than the thresholds for bacterial species delineation. In phylogenetic (based on 16S rRNA gene sequences) and phylogenomic trees

Caldicellulosiruptor acetigenus

,

Caldicellulosiruptor lactoaceticus

and

Caldicellulosiruptor kristjanssonii

clade together. The results of our analysis indicated that these three taxa are conspecific. Therefore,

Caldicellulosiruptor lactoaceticus

Mladenovska et al. 1997 and

Caldicellulosiruptor kristjanssonii

Bredholt et al. 1999 should be reclassified as later heterotypic synonyms of

Caldicellulosiruptor acetigenus

(Nielsen et al. 1994) Onyenwoke et al. 2006.
The emerging role of perivascular cells (pericytes) in viral pathogenesis
Authors: Butsabong Teemapron , Felippe Mariana , Campagnolo Paola , Maringer Kevin
Published: August 2021

Viruses may exploit the cardiovascular system to facilitate transmission or within-host dissemination, and the symptoms of many viral diseases stem at least in part from a loss of vascular integrity. The microvascular architecture is comprised of an endothelial cell barrier ensheathed by perivascular cells (pericytes). Pericytes are antigen-presenting cells (APCs) and play crucial roles in angiogenesis and the maintenance of microvascular integrity through complex reciprocal contact-mediated and paracrine crosstalk with endothelial cells. We here review the emerging ways that viruses interact with pericytes and pay consideration to how these interactions influence microvascular function and viral pathogenesis. Major outcomes of virus-pericyte interactions include vascular leakage or haemorrhage, organ tropism facilitated by barrier disruption, including viral penetration of the blood-brain barrier and placenta, as well as inflammatory, neurological, cognitive and developmental sequelae. The underlying pathogenic mechanisms may include direct infection of pericytes, pericyte modulation by secreted viral gene products and/or the dysregulation of paracrine signalling from or to pericytes. Viruses we cover include the herpesvirus human cytomegalovirus (HCMV, Human betaherpesvirus 5), the retrovirus human immunodeficiency virus (HIV; causative agent of acquired immunodeficiency syndrome, AIDS, and HIV-associated neurocognitive disorder, HAND), the flaviviruses dengue virus (DENV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV), and the coronavirus severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2; causative agent of coronavirus disease 2019, COVID-19). We touch on promising pericyte-focussed therapies for treating the diseases caused by these important human pathogens, many of which are emerging viruses or are causing new or long-standing global pandemics.
Prevalence of bovine astroviruses and their genotypes in sampled Chinese calves with and without diarrhoea
Authors: Zhu Jie , Qi Mingpu , Jiang Chuanwen , Peng Yongchong , Peng Qingjie , Chen Yingyu , Hu Changmin , Chen Jianguo , Chen Xi , Chen Huanchun , Guo Aizhen
Published: August 2021

Bovine astrovirus (BoAstV) belongs to genus Mamastravirus (MAstV). It can be detected in the faeces of both diarrhoeal and healthy calves. However, its prevalence, genetic diversity, and association with cattle diarrhoea are poorly understood. In this study, faecal samples of 87 diarrhoeal and 77 asymptomatic calves from 20 farms in 12 provinces were collected, and BoAstV was detected with reverse transcription-polymerase chain reaction (RT-PCR). The overall prevalence rate of this virus in diarrhoeal and asymptomatic calves was 55.17 % (95 % CI: 44.13, 65.85 %) and 36.36 % (95 % CI: 25.70, 48.12 %), respectively, indicating a correlation between BoAstV infection and calf diarrhoea (OR=2.15, P=0.024). BoAstV existed mainly in the form of co-infection (85.53 %) with one to five of nine viruses, and there was a strong positive correlation between BoAstV co-infection and calf diarrhoea (OR=2.83, P=0.004). Binary logistic regression analysis confirmed this correlation between BoAstV co-infection and calf diarrhoea (OR=2.41, P=0.038). The co-infection of BoAstV and bovine rotavirus (BRV) with or without other viruses accounted for 70.77 % of all the co-infection cases. The diarrhoea risk for the calves co-infected with BoAstV and BRV was 8.14-fold higher than that for the calves co-infected with BoAstV and other viruses (OR=8.14, P=0.001). Further, the co-infection of BoAstV/BRV/bovine kobuvirus (BKoV) might increase the risk of calf diarrhoea by 14.82-fold, compared with that of BoAstV and other viruses (OR=14.82, P <0.001). Then, nearly complete genomic sequences of nine BoAstV strains were assembled by using next-generation sequencing (NGS) method. Sequence alignment against known astrovirus (AstV) strains at the levels of both amino acids and nucleotides showed a high genetic diversity. Four genotypes were identified, including two known genotypes MAstV-28 (n=3) and MAstV-33 (n=2) and two novel genotypes designated tentatively as MAstV-34 (n=1) and MAstV-35 (n=3). In addition, seven out of nine BoAstV strains showed possible inter-genotype recombination and cross-species recombination. Therefore, our results increase the knowledge about the prevalence and the genetic evolution of BoAstV and provide evidence for the association between BoAstV infection and calf diarrhoea.
Treatment with Soluble CD24 Attenuates COVID-19-Associated Systemic Immunopathology
Authors: Song No-Joon , Allen Carter , Vilgelm Anna E. , Riesenberg Brian P. , Weller Kevin P. , Reynolds Kelsi , Chakravarthy Karthik B. , Kumar Amrendra , Khatiwada Aastha , Sun Zequn , Ma Anjun , Chang Yuzhou , Yusuf Mohamed , Li Anqi , Zeng Cong , Evans John P. , Bucci Donna , Gunasena Manuja , Xu Menglin , Liyanage Namal P.M. , Bolyard Chelsea , Velegraki Maria , Liu Shan-Lu , Ma Qin , Devenport Martin , Liu Yang , Zheng Pan , Malvestutto Carlos D. , Chung Dongjun , Li Zihai
Published: August 2021

BACKGROUND

SARS-CoV-2 causes COVID-19 through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns (DAMPs) and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) is able to blunt the broad inflammatory response induced by DAMPs in multiple models. A recent randomized phase III trial evaluating the impact of CD24Fc in patients with severe COVID-19 demonstrated encouraging clinical efficacy.

METHODS

We studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial (NCT04317040) collected before and after treatment with CD24Fc or placebo. We performed high dimensional spectral flow cytometry analysis of peripheral blood mononuclear cells and measured the levels of a broad array of cytokines and chemokines. A systems analytical approach was used to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19.

FINDINGS

Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found systemic hyper-activation of multiple cellular compartments in the placebo group, including CD8+ T cells, CD4+ T cells, and CD56+ NK cells. By contrast, CD24Fc-treated patients demonstrated blunted systemic inflammation, with a return to homeostasis in both NK and T cells within days without compromising the ability of patients to mount an effective anti-Spike protein antibody response. A single dose of CD24Fc significantly attenuated induction of the systemic cytokine response, including expression of IL-10 and IL-15, and diminished the coexpression and network connectivity among extensive circulating inflammatory cytokines, the parameters associated with COVID-19 disease severity.

INTERPRETATION

Our data demonstrates that CD24Fc treatment rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19.

FUNDING

NIH
Comparative study of protein aggregation propensity and mutation tolerance between naked mole-rat and mouse
Authors: Besse Savandara , Poujol Raphaël , Hussin Julie G.
Published: August 2021

The molecular mechanisms of aging and life expectancy have been studied in model organisms with short lifespans. However, long-lived species may provide insights into successful strategies of healthy aging, potentially opening the door for novel therapeutic interventions in age-related diseases. Notably, naked mole-rats, the longest-lived rodent, present attenuated aging phenotypes in comparison to mice. Their resistance toward oxidative stress has been proposed as one hallmark of their healthy aging, suggesting their ability to maintain cell homeostasis, and specifically their protein homeostasis. To identify the general principles behind their protein homeostasis robustness, we compared the aggregation propensity and mutation tolerance of naked mole-rat and mouse orthologous proteins. Our analysis showed no proteome-wide differential effects in aggregation propensity and mutation tolerance between these species, but several subsets of proteins with a significant difference in aggregation propensity. We found an enrichment of proteins with higher aggregation propensity in naked mole-rat involved the inflammasome complex, and in nucleic acid binding. On the other hand, proteins with lower aggregation propensity in naked mole-rat have a significantly higher mutation tolerance compared to the rest of the proteins. Among them, we identified proteins known to be associated with neurodegenerative and age-related diseases. These findings highlight the intriguing hypothesis about the capacity of the naked mole-rat proteome to delay aging through its proteomic intrinsic architecture.

Significance statement

The molecular mechanisms behind naked mole-rat longevity are still poorly understood. Here, we address how the proteome architecture can help delay the onset of aging in naked mole-rat by studying properties that modulate protein aggregation. We identify ∼1,000 proteins with significant differences in aggregation propensity and mutation tolerance involved in processes known to be dysfunctional during aging. These findings highlight how evolutionary adaptations in protein aggregation in distinct biological processes could explain naked mole-rat longevity.