bluuebunny/crossref_metadata_2025 huggingface dataset:
Defective dystrophic thymus determines degenerative changes in skeletal muscle
Authors: Farini Andrea , Sitzia Clementina , Villa Chiara , Cassani Barbara , Tripodi Luana , Legato Mariella , Belicchi Marzia , Bella Pamela , Lonati Caterina , Gatti Stefano , Cerletti Massimiliano , Torrente Yvan
Published: April 2021

In Duchenne muscular dystrophy (DMD), sarcolemma fragility and myofiber necrosis produce cellular debris that attract inflammatory cells. Macrophages and T-lymphocytes infiltrate muscles in response to damage-associated molecular pattern signalling and the release of TNF-α, TGF-β and interleukins prevent skeletal muscle improvement from the inflammation. This immunological scenario was extended by the discovery of a specific response to muscle antigens and a role for regulatory T cells (Tregs) in muscle regeneration. Normally, autoimmunity is avoided by autoreactive T-lymphocyte deletion within thymus, while in the periphery Tregs monitor effector T-cells escaping from central regulatory control. Here, we report impairment of thymus architecture of mdx mice together with decreased expression of ghrelin, autophagy dysfunction and AIRE down-regulation. Transplantation of dystrophic thymus in recipient nude mice determine the up-regulation of inflammatory/fibrotic markers, marked metabolic breakdown that leads to muscle atrophy and loss of force. These results indicate that involution of dystrophic thymus exacerbates muscular dystrophy by altering central immune tolerance.
Primate ventral striatum maintains neural representations of the value of previously rewarded objects for habitual seeking
Authors: Kang Joonyoung , Kim Hyeji , Hwang Seong Hwan , Han Minjun , Lee Sue-Hyun , Kim Hyoung F.
Published: April 2021

The ventral striatum (VS) is considered a key region that flexibly updates recent changes in reward values for habit learning. However, this update process may not serve to maintain learned habitual behaviors, which are insensitive to value changes. Here, using fMRI in humans and single-unit electrophysiology in macaque monkeys we report another role of the primate VS: that the value memory subserving habitual seeking is stably maintained in the VS. Days after object-value associative learning, human and monkey VS continue to show increased responses to previously rewarded objects, even when no immediate reward outcomes are expected. The similarity of neural response patterns to each rewarded object increases after learning among participants who display habitual seeking. Our data show that long-term memory of high-valued objects is retained as a single representation in the VS and may be utilized to evaluate visual stimuli automatically to guide habitual behavior.
ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H+-ATPases is essential for brain development in humans and mice
Authors: Aoto Kazushi , Kato Mitsuhiro , Akita Tenpei , Nakashima Mitsuko , Mutoh Hiroki , Akasaka Noriyuki , Tohyama Jun , Nomura Yoshiko , Hoshino Kyoko , Ago Yasuhiko , Tanaka Ryuta , Epstein Orna , Ben-Haim Revital , Heyman Eli , Miyazaki Takehiro , Belal Hazrat , Takabayashi Shuji , Ohba Chihiro , Takata Atsushi , Mizuguchi Takeshi , Miyatake Satoko , Miyake Noriko , Fukuda Atsuo , Matsumoto Naomichi , Saitsu Hirotomo
Published: April 2021

Vacuolar H+-ATPases (V-ATPases) transport protons across cellular membranes to acidify various organelles. ATP6V0A1 encodes the a1-subunit of the V0 domain of V-ATPases, which is strongly expressed in neurons. However, its role in brain development is unknown. Here we report four individuals with developmental and epileptic encephalopathy with ATP6V0A1 variants: two individuals with a de novo missense variant (R741Q) and the other two individuals with biallelic variants comprising one almost complete loss-of-function variant and one missense variant (A512P and N534D). Lysosomal acidification is significantly impaired in cell lines expressing three missense ATP6V0A1 mutants. Homozygous mutant mice harboring human R741Q (Atp6v0a1R741Q) and A512P (Atp6v0a1A512P) variants show embryonic lethality and early postnatal mortality, respectively, suggesting that R741Q affects V-ATPase function more severely. Lysosomal dysfunction resulting in cell death, accumulated autophagosomes and lysosomes, reduced mTORC1 signaling and synaptic connectivity, and lowered neurotransmitter contents of synaptic vesicles are observed in the brains of Atp6v0a1A512P/A512P mice. These findings demonstrate the essential roles of ATP6V0A1/Atp6v0a1 in neuronal development in terms of integrity and connectivity of neurons in both humans and mice.
Author Correction: In situ conversion of defective Treg into SuperTreg cells to treat advanced IPEX-like disorders in mice
Authors: Li Yongqin , Chen Yuxin , Mao Shaoshuai , Kaundal Ravinder , Jing Zhengyu , Chen Qin , Wang Xinxin , Xia Jing , Liu Dahai , Sun Jianlong , Wang Haopeng , Chi Tian
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22629-8
Reprogrammable and high-precision holographic optical addressing of trapped ions for scalable quantum control
Authors: Shih Chung-You , Motlakunta Sainath , Kotibhaskar Nikhil , Sajjan Manas , Hablützel Roland , Islam Rajibul
Published: April 2021

High-precision, individually programmable manipulation of quantum particles is crucial for scaling up quantum information processing (QIP) systems such as laser-cooled trapped-ions. However, restricting undesirable “crosstalk” in optical manipulation of ion qubits is fundamentally challenging due to micron-level inter-ion separation. Further, inhomogeneous ion spacing and high susceptibility to aberrations at UV wavelengths suitable for most ion-species pose severe challenges. Here, we demonstrate high-precision individual addressing (λ = 369.5 nm) of Yb+ using a reprogrammable Fourier hologram. The precision is achieved through in-situ aberration characterization via the trapped ion, and compensating (to λ/20) with the hologram. Using an iterative Fourier transformation algorithm (IFTA), we demonstrate an ultra-low (<10−4) intensity crosstalk error in creating arbitrary pair-wise addressing profiles, suitable for over fifty ions. This scheme relies on standard commercial hardware, can be readily extended to over a hundred ions, and adapted to other ion-species and quantum platforms.
Superconductor-to-metal transition in overdoped cuprates
Authors: Li Zi-Xiang , Kivelson Steven A. , Lee Dung-Hai
Published: April 2021

We present a theoretical framework for understanding the behavior of the normal and superconducting states of overdoped cuprate high temperature superconductors in the vicinity of the doping-tuned quantum superconductor-to-metal transition. The key ingredients on which we focus are d-wave pairing, a flat antinodal dispersion, and disorder. Even for homogeneous disorder, these lead to effectively granular superconducting correlations and a superconducting transition temperature determined in large part by the superfluid stiffness rather than the pairing scale.
Author Correction: Dense sampling of bird diversity increases power of comparative genomics
Authors: Feng Shaohong , Stiller Josefin , Deng Yuan , Armstrong Joel , Fang Qi , Reeve Andrew Hart , Xie Duo , Chen Guangji , Guo Chunxue , Faircloth Brant C. , Petersen Bent , Wang Zongji , Zhou Qi , Diekhans Mark , Chen Wanjun , Andreu-Sánchez Sergio , Margaryan Ashot , Howard Jason Travis , Parent Carole , Pacheco George , Sinding Mikkel-Holger S. , Puetz Lara , Cavill Emily , Ribeiro Ângela M. , Eckhart Leopold , Fjeldså Jon , Hosner Peter A. , Brumfield Robb T. , Christidis Les , Bertelsen Mads F. , Sicheritz-Ponten Thomas , Tietze Dieter Thomas , Robertson Bruce C. , Song Gang , Borgia Gerald , Claramunt Santiago , Lovette Irby J. , Cowen Saul J. , Njoroge Peter , Dumbacher John Philip , Ryder Oliver A. , Fuchs Jérôme , Bunce Michael , Burt David W. , Cracraft Joel , Meng Guanliang , Hackett Shannon J. , Ryan Peter G. , Jønsson Knud Andreas , Jamieson Ian G. , da Fonseca Rute R. , Braun Edward L. , Houde Peter , Mirarab Siavash , Suh Alexander , Hansson Bengt , Ponnikas Suvi , Sigeman Hanna , Stervander Martin , Frandsen Paul B. , van der Zwan Henriette , van der Sluis Rencia , Visser Carina , Balakrishnan Christopher N. , Clark Andrew G. , Fitzpatrick John W. , Bowman Reed , Chen Nancy , Cloutier Alison , Sackton Timothy B. , Edwards Scott V. , Foote Dustin J. , Shakya Subir B. , Sheldon Frederick H. , Vignal Alain , Soares André E. R. , Shapiro Beth , González-Solís Jacob , Ferrer-Obiol Joan , Rozas Julio , Riutort Marta , Tigano Anna , Friesen Vicki , Dalén Love , Urrutia Araxi O. , Székely Tamás , Liu Yang , Campana Michael G. , Corvelo André , Fleischer Robert C. , Rutherford Kim M. , Gemmell Neil J. , Dussex Nicolas , Mouritsen Henrik , Thiele Nadine , Delmore Kira , Liedvogel Miriam , Franke Andre , Hoeppner Marc P. , Krone Oliver , Fudickar Adam M. , Milá Borja , Ketterson Ellen D. , Fidler Andrew Eric , Friis Guillermo , Parody-Merino Ángela M. , Battley Phil F. , Cox Murray P. , Lima Nicholas Costa Barroso , Prosdocimi Francisco , Parchman Thomas Lee , Schlinger Barney A. , Loiselle Bette A. , Blake John G. , Lim Haw Chuan , Day Lainy B. , Fuxjager Matthew J. , Baldwin Maude W. , Braun Michael J. , Wirthlin Morgan , Dikow Rebecca B. , Ryder T. Brandt , Camenisch Glauco , Keller Lukas F. , DaCosta Jeffrey M. , Hauber Mark E. , Louder Matthew I. M. , Witt Christopher C. , McGuire Jimmy A. , Mudge Joann , Megna Libby C. , Carling Matthew D. , Wang Biao , Taylor Scott A. , Del-Rio Glaucia , Aleixo Alexandre , Vasconcelos Ana Tereza Ribeiro , Mello Claudio V. , Weir Jason T. , Haussler David , Li Qiye , Yang Huanming , Wang Jian , Lei Fumin , Rahbek Carsten , Gilbert M. Thomas P. , Graves Gary R. , Jarvis Erich D. , Paten Benedict , Zhang Guojie
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03473-8.
Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients
Authors: de la Morena-Barrio María Eugenia , Bravo-Pérez Carlos , Miñano Antonia , de la Morena-Barrio Belén , Fernandez-Perez María Piedad , Bernal Enrique , Gómez-Verdu José Miguel , Herranz María Teresa , Vicente Vicente , Corral Javier , Lozano María Luisa
Published: April 2021

SARS-CoV-2 infection increases the risk of thrombosis by different mechanisms not fully characterized. Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with thromboembolic risk and unfavorable prognosis. We aim to systematically and comprehensively evaluate the association between thrombin generation parameters and the inflammatory and hypercoagulable state, as well as their prognostic value in COVID-19 patients. A total of 127 hospitalized patients with confirmed COVID-19, 24 hospitalized patients with SARS-CoV-2-negative pneumonia and 12 healthy subjects were included. Clinical characteristics, thrombin generation triggered by tissue factor with and without soluble thrombomodulin, and also by silica, as well as other biochemical parameters were assessed. Despite the frequent use of heparin, COVID-19 patients had similar thrombin generation to healthy controls. In COVID-19 patients, the thrombin generation lag-time positively correlated with markers of cell lysis (LDH), inflammation (CRP, IL-6) and coagulation (D-dimer), while the endogenous thrombin potential (ETP) inversely correlated with D-dimer and LDH, and positively correlated with fibrinogen levels. Patients with more prolonged lag-time and decreased ETP had higher peak ISTH-DIC scores, and had more severe disease (vascular events and death). The ROC curve and Kaplan Meier estimate indicated that the D-dimer/ETP ratio was associated with in-hospital mortality (HR 2.5; p = 0.006), and with the occurrence of major adverse events (composite end-point of vascular events and death) (HR 2.38; p = 0.004). The thrombin generation ETP and lag-time variables correlate with thromboinflammatory markers, and the D-dimer/ETP ratio can predict major adverse events in COVID-19.
Chest beats as an honest signal of body size in male mountain gorillas (Gorilla beringei beringei)
Authors: Wright Edward , Grawunder Sven , Ndayishimiye Eric , Galbany Jordi , McFarlin Shannon C. , Stoinski Tara S. , Robbins Martha M.
Published: April 2021

Acoustic signals that reliably indicate body size, which usually determines competitive ability, are of particular interest for understanding how animals assess rivals and choose mates. Whereas body size tends to be negatively associated with formant dispersion in animal vocalizations, non-vocal signals have received little attention. Among the most emblematic sounds in the animal kingdom is the chest beat of gorillas, a non-vocal signal that is thought to be important in intra and inter-sexual competition, yet it is unclear whether it reliably indicates body size. We examined the relationship among body size (back breadth), peak frequency, and three temporal characteristics of the chest beat: duration, number of beats and beat rate from sound recordings of wild adult male mountain gorillas. Using linear mixed models, we found that larger males had significantly lower peak frequencies than smaller ones, but we found no consistent relationship between body size and the temporal characteristics measured. Taken together with earlier findings of positive correlations among male body size, dominance rank and reproductive success, we conclude that the gorilla chest beat is an honest signal of competitive ability. These results emphasize the potential of non-vocal signals to convey important information in mammal communication.
Effects of both climate change and human water demand on a highly threatened damselfly
Authors: Khelifa Rassim , Mahdjoub Hayat , Baaloudj Affef , Cannings Robert A. , Samways Michael J.
Published: April 2021

While climate change severely affects some aquatic ecosystems, it may also interact with anthropogenic factors and exacerbate their impact. In dry climates, dams can cause hydrological drought during dry periods following a great reduction in dam water discharge. However, impact of these severe hydrological droughts on lotic fauna is poorly documented, despite climate change expected to increase drought duration and intensity. We document here how dam water discharge was affected by climate variability during 2011–2018 in a highly modified watershed in northeastern Algeria, and how an endemic endangered lotic damselfly, Calopteryx exul Selys, 1853 (Odonata: Calopterygidae), responded to hydrological drought episodes. Analysis was based on a compilation of data on climate (temperature, precipitation, and drought index), water dam management (water depth and discharge volume and frequency), survey data on C. exul occurrence, and capture–mark–recapture (CMR) of adults. The study period was characterized by a severe drought between 2014 and 2017, which led to a lowering of dam water depth and reduction of discharge into the river, with associated changes in water chemistry, particularly during 2017 and 2018. These events could have led to the extirpation of several populations of C. exul in the Seybouse River (Algeria). CMR surveys showed that the species was sensitive to water depth fluctuations, avoiding low and high water levels (drought and flooding). The study shows that climate change interacts with human water requirements and affects river flow regimes, water chemistry and aquatic fauna. As drought events are likely to increase in the future, the current study highlights the need for urgent new management plans for lotic habitats to maintain this species and possible others.
Single molecule network analysis identifies structural changes to caveolae and scaffolds due to mutation of the caveolin-1 scaffolding domain
Authors: Wong Timothy H. , Khater Ismail M. , Joshi Bharat , Shahsavari Mona , Hamarneh Ghassan , Nabi Ivan R.
Published: April 2021

Caveolin-1 (CAV1), the caveolae coat protein, also associates with non-caveolar scaffold domains. Single molecule localization microscopy (SMLM) network analysis distinguishes caveolae and three scaffold domains, hemispherical S2 scaffolds and smaller S1B and S1A scaffolds. The caveolin scaffolding domain (CSD) is a highly conserved hydrophobic region that mediates interaction of CAV1 with multiple effector molecules. F92A/V94A mutation disrupts CSD function, however the structural impact of CSD mutation on caveolae or scaffolds remains unknown. Here, SMLM network analysis quantitatively shows that expression of the CAV1 CSD F92A/V94A mutant in CRISPR/Cas CAV1 knockout MDA-MB-231 breast cancer cells reduces the size and volume and enhances the elongation of caveolae and scaffold domains, with more pronounced effects on S2 and S1B scaffolds. Convex hull analysis of the outer surface of the CAV1 point clouds confirms the size reduction of CSD mutant CAV1 blobs and shows that CSD mutation reduces volume variation amongst S2 and S1B CAV1 blobs at increasing shrink values, that may reflect retraction of the CAV1 N-terminus towards the membrane, potentially preventing accessibility of the CSD. Detection of point mutation-induced changes to CAV1 domains highlights the utility of SMLM network analysis for mesoscale structural analysis of oligomers in their native environment.
A longitudinal residential relocation study of changes in street layout and physical activity
Authors: McCormack Gavin R. , Koohsari Mohammad Javad , Vena Jennifer E. , Oka Koichiro , Nakaya Tomoki , Chapman Jonathan , Martinson Ryan , Matsalla Graham
Published: April 2021

Few longitudinal residential relocation studies have explored associations between urban form and physical activity, and none has used the Space Syntax theory. Using a Canadian longitudinal dataset (n = 5944), we estimated: (1) differences in physical activity between non-movers, and those relocating to neighbourhoods with less or more integrated street layouts, and; (2) associations between changes in street layout integration exposure and differences in physical activity. Adjusting for covariates, we found relative to non-movers, those who moved to more integrated neighbourhoods undertook significantly (p < .05) more leisure walking (27.3 min/week), moderate-intensity (45.7 min/week), and moderate-to-vigorous intensity physical activity (54.4 min/week). Among movers, a one-unit increase in the relative change in street integration exposure ([Street integration at follow-up—street integration at baseline]/street integration at baseline) was associated with a 7.5 min/week increase in leisure walking. Our findings suggest that urban design policies that improve neighbourhood street integration might encourage more physical activity in adults.
Mitochondria-targeted antioxidant protects against irradiation-induced salivary gland hypofunction
Authors: Liu Xibao , Subedi Krishna P. , Zheng Changyu , Ambudkar Indu
Published: April 2021

A severe consequence of radiation therapy in patients with head and neck cancer is persistent salivary gland hypofunction which causes xerostomia and oral infections. We previously showed that irradiation (IR) of salivary glands in mice triggers initial transient increases in mitochondrial reactive oxygen species (ROSmt), mitochondrial [Ca2+] ([Ca2+]mt), and activated caspase-3 in acinar cells. In contrast, loss of salivary secretion is persistent. Herein we assessed the role of ROSmt in radiation-induced irreversible loss of salivary gland function. We report that treatment of mice with the mitochondrial-targeted antioxidant, MitoTEMPO, resulted in almost complete protection of salivary gland secretion following either single (15 Gy) or fractionated (5 × 3 Gy) doses of irradiation. Salivary gland cells isolated from MitoTEMPO-treated, irradiated, mice displayed significant attenuation of the initial increases in ROSmt, ([Ca2+]mt, and activated caspase-3 as compared to cells from irradiated, but untreated, animals. Importantly, MitoTEMPO treatment prevented radiation-induced decrease in STIM1, consequently protecting store-operated Ca2+ entry which is critical for saliva secretion. Together, these findings identify the initial increase in ROSmt, that is induced by irradiation, as a critical driver of persistent salivary gland hypofunction. We suggest that the mitochondrially targeted antioxidant, MitoTEMPO, can be potentially important in preventing IR-induced salivary gland dysfunction.
Thymol nanoemulsion promoted broiler chicken’s growth, gastrointestinal barrier and bacterial community and conferred protection against Salmonella Typhimurium
Authors: Ibrahim Doaa , Abdelfattah-Hassan Ahmed , Badawi M. , Ismail Tamer Ahmed , Bendary Mahmoud M. , Abdelaziz Adel M. , Mosbah Rasha A. , Mohamed Dalia Ibrahim , Arisha Ahmed H. , El-Hamid Marwa I. Abd
Published: April 2021

The present study involved in vivo evaluation of the growth promoting effects of thymol and thymol nanoemulsion and their protection against Salmonella Typhimurium infection in broilers. One-day old 2400 chicks were randomly divided into eight groups; negative and positive control groups fed basal diet without additives and thymol and thymol nanoemulsion groups (0.25, 0.5 and 1% each). At d 23, all chicks except negative control were challenged with S. Typhimurium. Over the total growing period, birds fed 1% thymol nanoemulsion showed better growth performance even after S. Typhimurium challenge, which came parallel with upregulation of digestive enzyme genes (AMY2A, PNLIP and CCK). Additionally, higher levels of thymol nanoemulsion upregulated the expression of MUC-2, FABP2, IL-10, IgA and tight junction proteins genes and downregulated IL-2 and IL-6 genes expression. Moreover, 1% thymol nanoemulsion, and to lesser extent 0.5% thymol nanoemulsion and 1% thymol, corrected the histological alterations of cecum and liver postinfection. Finally, supplementation of 1% thymol, 0.5 and 1% thymol nanoemulsion led to increased Lactobacilli counts and decreased S. Typhimurium populations and downregulated invA gene expression postinfection. This first report of supplying thymol nanoemulsion in broiler diets proved that 1% nano-thymol is a potential growth promoting and antibacterial agent.
Robenacoxib shows efficacy for the treatment of chronic degenerative joint disease-associated pain in cats: a randomized and blinded pilot clinical trial
Authors: Adrian Derek , King Jonathan N. , Parrish Rudolph S. , King Stephen B. , C. Budsberg Steven , Gruen Margaret E. , Lascelles B. Duncan X.
Published: April 2021

The main objective of this pilot clinical trial was to evaluate outcome measures for the assessment of the nonsteroidal anti-inflammatory drug (NSAID) robenacoxib in cats with degenerative joint disease-associated pain (DJD-pain). Otherwise healthy cats (n = 109) with DJD-pain entered a parallel group, randomized, blinded clinical trial. Cats received placebo (P) or robenacoxib (R) for two consecutive 3-week periods. Treatment groups were PP, RR, and RP. Actimetry and owner-assessment data were collected. Data were analyzed using mixed-effects and generalized mixed-effects linear models. Activity data showed high within-cat and between-cat variability, and 82.4% of the values were zero. Compared to placebo, mean total activity was higher (5.7%) in robenacoxib-treated cats (p = 0.24); for the 80th percentile of activity, more robenacoxib-treated cats had a > 10% increase in activity after 3 (p = 0.046) and 6 weeks (p = 0.026). Robenacoxib treatment significantly decreased owner-assessed disability, (p = 0.01; 49% reduction in disability; effect size ~ 0.3), and improved temperament (p = 0.0039) and happiness (p = 0.021) after 6 weeks. More robenacoxib-treated cats were successes at 6 weeks (p = 0.018; NNT: 3.8). Adverse effect frequencies were similar across groups. Results identified suitable endpoints for confirmatory studies, while also indicating efficacy of robenacoxib in cats with DJD-pain.
Heterogeneous interventions reduce the spread of COVID-19 in simulations on real mobility data
Authors: Wang Haotian , Ghosh Abhirup , Ding Jiaxin , Sarkar Rik , Gao Jie
Published: April 2021

Major interventions have been introduced worldwide to slow down the spread of the SARS-CoV-2 virus. Large scale lockdown of human movements are effective in reducing the spread, but they come at a cost of significantly limited societal functions. We show that natural human movements are statistically diverse, and the spread of the disease is significantly influenced by a small group of active individuals and gathering venues. We find that interventions focused on these most mobile individuals and popular venues reduce both the peak infection rate and the total infected population while retaining high social activity levels. These trends are seen consistently in simulations with real human mobility data of different scales, resolutions, and modalities from multiple cities across the world. The observation implies that compared to broad sweeping interventions, more heterogeneous strategies that are targeted based on the network effects in human mobility provide a better balance between pandemic control and regular social activities.
A novel, hands-free ultrasound patch for continuous monitoring of quantitative Doppler in the carotid artery
Authors: Kenny Jon-Émile S. , Munding Chelsea E. , Eibl Joseph K. , Eibl Andrew M. , Long Bradley F. , Boyes Aaron , Yin Jianhua , Verrecchia Pietro , Parrotta Matthew , Gatzke Ronald , Magnin Paul A. , Burns Peter N. , Foster F. Stuart , Demore Christine E. M.
Published: April 2021

Quantitative Doppler ultrasound of the carotid artery has been proposed as an instantaneous surrogate for monitoring rapid changes in left ventricular output. Tracking immediate changes in the arterial Doppler spectrogram has value in acute care settings such as the emergency department, operating room and critical care units. We report a novel, hands-free, continuous-wave Doppler ultrasound patch that adheres to the neck and tracks Doppler blood flow metrics in the common carotid artery using an automated algorithm. String and blood-mimicking test objects demonstrated that changes in velocity were accurately measured using both manually and automatically traced Doppler velocity waveforms. In a small usability study with 22 volunteer users (17 clinical, 5 lay), all users were able to locate the carotid Doppler signal on a volunteer subject, and, in a subsequent survey, agreed that the device was easy to use. To illustrate potential clinical applications of the device, the Doppler ultrasound patch was used on a healthy volunteer undergoing a passive leg raise (PLR) as well as on a congestive heart failure patient at resting baseline. The wearable carotid Doppler patch holds promise because of its ease-of-use, velocity measurement accuracy, and ability to continuously record Doppler spectrograms over many cardiac and respiratory cycles.
Development and characterization of Nb3Sn/Al2O3 superconducting multilayers for particle accelerators
Authors: Sundahl Chris , Makita Junki , Welander Paul B. , Su Yi-Feng , Kametani Fumitake , Xie Lin , Zhang Huimin , Li Lian , Gurevich Alex , Eom Chang-Beom
Published: April 2021

Superconducting radio-frequency (SRF) resonator cavities provide extremely high quality factors > 1010 at 1–2 GHz and 2 K in large linear accelerators of high-energy particles. The maximum accelerating field of SRF cavities is limited by penetration of vortices into the superconductor. Present state-of-the-art Nb cavities can withstand up to 50 MV/m accelerating gradients and magnetic fields of 200–240 mT which destroy the low-dissipative Meissner state. Achieving higher accelerating gradients requires superconductors with higher thermodynamic critical fields, of which Nb3Sn has emerged as a leading material for the next generation accelerators. To overcome the problem of low vortex penetration field in Nb3Sn, it has been proposed to coat Nb cavities with thin film Nb3Sn multilayers with dielectric interlayers. Here, we report the growth and multi-technique characterization of stoichiometric Nb3Sn/Al2O3 multilayers with good superconducting and RF properties. We developed an adsorption-controlled growth process by co-sputtering Nb and Sn at high temperatures with a high overpressure of Sn. The cross-sectional scanning electron transmission microscope images show no interdiffusion between Al2O3 and Nb3Sn. Low-field RF measurements suggest that our multilayers have quality factor comparable with cavity-grade Nb at 4.2 K. These results provide a materials platform for the development and optimization of high-performance SIS multilayers which could overcome the intrinsic limits of the Nb cavity technology.
The influence of biophysical parameters in a biomechanical model of cortical folding patterns
Authors: Wang Xiaoyu , Lefèvre Julien , Bohi Amine , Harrach Mariam Al , Dinomais Mickael , Rousseau François
Published: April 2021

Abnormal cortical folding patterns, such as lissencephaly, pachygyria and polymicrogyria malformations, may be related to neurodevelopmental disorders. In this context, computational modeling is a powerful tool to provide a better understanding of the early brain folding process. Recent studies based on biomechanical modeling have shown that mechanical forces play a crucial role in the formation of cortical convolutions. However, the effect of biophysical parameters in these models remain unclear. In this paper, we investigate the effect of the cortical growth, the initial geometry and the initial cortical thickness on folding patterns. In addition, we not only use several descriptors of the folds such as the dimensionless mean curvature, the surface-based three-dimensional gyrification index and the sulcal depth, but also propose a new metric to quantify the folds orientation. The results demonstrate that the cortical growth mode does almost not affect the complexity degree of surface morphology; the variation in the initial geometry changes the folds orientation and depth, and in particular, the slenderer the shape is, the more folds along its longest axis could be seen and the deeper the sulci become. Moreover, the thinner the initial cortical thickness is, the higher the spatial frequency of the folds is, but the shallower the sulci become, which is in agreement with the previously reported effects of cortical thickness.
Anthracene induces oxidative stress and activation of antioxidant and detoxification enzymes in Ulva lactuca (Chlorophyta)
Authors: González Alberto , Vidal Constanza , Espinoza Daniela , Moenne Alejandra
Published: April 2021

In order to analyze whether the marine macroalga Ulva lactuca can absorb and metabolize anthracene (ANT), the alga was cultivated with 5 µM ANT for 0–72 h, and the level of ANT was detected in the culture medium, and in the alga. The level of ANT rapidly decreased in the culture medium reaching a minimal level at 6 h, and rapidly increased in the alga reaching a maximal level at 12 h and then decreased to reach a minimal level at 48 h of culture. In addition, ANT induced an increase in hydrogen peroxide that remained until 72 h and a higher increase in superoxide anions that reach a maximal level at 24 h and remained unchanged until 72 h, indicating that ANT induced an oxidative stress condition. ANT induced an increase in lipoperoxides that reached a maximal level at 24 h and decreased at 48 h indicating that oxidative stress caused membrane damage. The activity of antioxidant enzymes SOD, CAT, AP, GR and GP increased in the alga treated with ANT whereas DHAR remained unchanged. The level of transcripts encoding these antioxidant enzymes increased and those encoding DHAR did not change. Inhibitors of monooxygenases, dioxygenases, polyphenol oxidases, glutathione-S-transferases and sulfotransferases induced an increase in the level of ANT in the alga cultivated for 24 h. These results strongly suggest that ANT is rapidly absorbed and metabolized in U. lactuca and the latter involves Phase I and II metabolizing enzymes.
Limnological response from high-altitude wetlands to the water supply in the Andean Altiplano
Authors: García-Sanz Ignacio , Heine-Fuster Inger , Luque José A. , Pizarro Héctor , Castillo Rodrigo , Pailahual Matías , Prieto Manuel , Pérez-Portilla Pablo , Aránguiz-Acuña Adriana
Published: April 2021

The Andean Altiplano-Puna is located at an elevation of approximately 4000 m.a.s.l. and is delineated by the Western and the Eastern Andes Cordillera. The high-altitude wetlands (HAWs) in the Central Andes are unique ecosystems located in the Altiplano that provide many ecosystem services. The objective of this study was to characterize the spatial heterogeneity of the environmental conditions associated with varying hydrology of the HAW, Salar de Tara, in the Andean Altiplano. Sediment samples of up to 20 cm in depth were obtained from various salt flat sub-environments. The samples were analyzed using proxies for mineralogical and chemical composition, thermal analysis, and magnetic susceptibility. Diatom and ostracod communities were also identified and analyzed. The results reflected changes in the geochemistry, carbon content, mineralogy, and magnetic properties of the sediments that can be explained by variations in the sources of water input to the Salar de Tara. The sub-environments depend on the supply of water via the groundwater recharge of springs adjacent to the streamflow from the Zapaleri River, which promotes greater diversity and richness of genera. Our results suggest that water extraction at industrial levels greatly impacts the persistence of hydrologically connected HAWs, which concentrate a worldwide interest in brine mining.
Radiation-induced acute injury of intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in induction chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a prospective cohort study
Authors: Yao Zexin , Zhang Bing , Huang Jialin , Shi Lei , Cheng Biao
Published: April 2021

To address whether the addition of intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT) aggravate radiation-induced acute injury of locoregionally advanced nasopharyngeal carcinoma (LANPC) patients with induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). We conducted a prospective study of 182 patients in the stage III to IVb with biopsy-proven nonmetastatic LANPC who newly underwent radiotherapy and sequentially received IC, followed by CCRT at our institution. Occurring time of radiation-induced toxicities were estimated and compared using the Kaplan–Meier method and Log-rank test. The most severe acute toxicities included oral mucositis in 97.25% and dermatitis in 90.11%. Subset analysis revealed that Grade 3–4 acute dermatitis were significantly higher in the IMRT than 3D-CRT. Oral mucositis and dermatitis were the earliest occurrence of acute injuries (2 years: 60.44% and 17.58%). Patients in IMRT group achieved significantly lower risk of bone marrow toxicity, but higher risk of leukopenia and gastrointestinal injury. Multivariate analyses also demonstrated that IMRT, female gender and hepatitis were the independent prognostic factors for bone marrow toxicity. In a combined regimen of IC followed by CCRT for the treatment of LANPC, IMRT seems to be an aggressive technique with a trend towards increased gastrointestinal and hematological toxicities, but decreased bone marrow toxicity than those treated with 3D-CRT. This study provides a comprehensive summary of prospective evidence reporting the side effects in the management of LANPC patients. We quantify the occurrence risks of chemoradiotherapy-induced acute injuries through analysis of time-to-event.
Untuned broadband spiral micro-coils achieve sensitive multi-nuclear NMR TX/RX from microfluidic samples
Authors: Davoodi Hossein , Nordin Nurdiana , Munakata Hirokazu , Korvink Jan G. , MacKinnon Neil , Badilita Vlad
Published: April 2021

The low frequency plateau in the frequency response of an untuned micro-resonator permits broadband radio-frequency reception, albeit at the expense of optimal signal-to-noise ratio for a particular nucleus. In this contribution we determine useful figures of merit for broadband micro-coils, and thereby explore the parametric design space towards acceptable simultaneous excitation and reception of a microfluidic sample over a wide frequency band ranging from 13C to 1H, i.e., 125–500 MHz in an 11.74 T magnet. The detector achieves 37% of the performance of a comparably sized, tuned and matched resonator, and a linewidth of 17 ppb using standard magnet shims. The use of broadband detectors circumvents numerous difficulties introduced by multi-resonant RF detector circuits, including sample loading effects on matching, channel isolation, and field distortion.
Making the choice between bioelectrical impedance measures for body hydration status assessment
Authors: Davydov Dmitry M. , Boev Andrey , Gorbunov Stas
Published: April 2021

Situational or persistent body fluid deficit (i.e., de- or hypo-hydration) is considered a significant health risk factor. Bioimpedance analysis (BIA) has been suggested as an alternative to less reliable subjective and biochemical indicators of hydration status. The present study aimed to compare various BIA models in the prediction of direct measures of body compartments associated with hydration/osmolality. Fish (n = 20) was selected as a biological model for physicochemically measuring proximate body compartments associated with hydration such as water, dissolved proteins, and non-osseous minerals as the references or criterion points. Whole-body and segmental/local impedance measures were used to investigate a pool of BIA models, which were compared by Akaike Information Criterion in their ability to accurately predict the body components. Statistical models showed that ‘volumetric-based’ BIA measures obtained in parallel, such as distance2/Rp, could be the best approach in predicting percent of body moisture, proteins, and minerals in the whole-body schema. However, serially-obtained BIA measures, such as the ratio of the reactance to resistance and the resistance adjusted for distance between electrodes, were the best fitting in predicting the compartments in the segmental schema. Validity of these results should be confirmed on humans before implementation in practice.
Gaze-pattern similarity at encoding may interfere with future memory
Authors: klein Selle Nathalie , Gamer Matthias , Pertzov Yoni
Published: April 2021

Human brains have a remarkable ability to separate streams of visual input into distinct memory-traces. It is unclear, however, how this ability relates to the way these inputs are explored via unique gaze-patterns. Moreover, it is yet unknown how motivation to forget or remember influences the link between gaze similarity and memory. In two experiments, we used a modified directed-forgetting paradigm and either showed blurred versions of the encoded scenes (Experiment 1) or pink noise images (Experiment 2) during attempted memory control. Both experiments demonstrated that higher levels of across-stimulus gaze similarity relate to worse future memory. Although thisacross-stimulus interference effectwas unaffected by motivation, it depended on the perceptual overlap between stimuli and was more pronounced for different scene comparisons, than scene–pink noise comparisons. Intriguingly, these findings echo the pattern similarity effects from the neuroimaging literature and pinpoint a mechanism that could aid the regulation of unwanted memories.
Detection of chronic wasting disease in mule and white-tailed deer by RT-QuIC analysis of outer ear
Authors: Ferreira Natalia C. , Charco Jorge M. , Plagenz Jakob , Orru Christina D. , Denkers Nathanial D. , Metrick Michael A. , Hughson Andrew G. , Griffin Karen A. , Race Brent , Hoover Edward A. , Castilla Joaquín , Nichols Tracy A. , Miller Michael W. , Caughey Byron
Published: April 2021

Efforts to contain the spread of chronic wasting disease (CWD), a fatal, contagious prion disease of cervids, would be aided by the availability of additional diagnostic tools. RT-QuIC assays allow ultrasensitive detection of prion seeds in a wide variety of cervid tissues, fluids and excreta. The best documented antemortem diagnostic test involving RT-QuIC analysis targets lymphoid tissue in rectal biopsies. Here we have tested a more easily accessed specimen, ear pinna punches, using an improved RT-QuIC assay involving iron oxide magnetic extraction to detect CWD infections in asymptomatic mule and white-tailed deer. Comparison of multiple parts of the ear pinna indicated that a central punch spanning the auricular nerve provided the most consistent detection of CWD infection. When compared to results obtained from gold-standard retropharyngeal lymph node specimens, our RT-QuIC analyses of ear samples provided apparent diagnostic sensitivity (81%) and specificity (91%) that rivaled, or improved upon, those observed in previous analyses of rectal biopsies using RT-QuIC. These results provide evidence that RT-QuIC analysis of ear pinna punches may be a useful approach to detecting CWD infections in cervids.
Novel approach to modeling high-frequency activity data to assess therapeutic effects of analgesics in chronic pain conditions
Authors: Xu Zekun , Laber Eric , Staicu Ana-Maria , Lascelles B. Duncan X.
Published: April 2021

Osteoarthritis (OA) is a chronic condition often associated with pain, affecting approximately fourteen percent of the population, and increasing in prevalence. A globally aging population have made treating OA-associated pain as well as maintaining mobility and activity a public health priority. OA affects all mammals, and the use of spontaneous animal models is one promising approach for improving translational pain research and the development of effective treatment strategies. Accelerometers are a common tool for collecting high-frequency activity data on animals to study the effects of treatment on pain related activity patterns. There has recently been increasing interest in their use to understand treatment effects in human pain conditions. However, activity patterns vary widely across subjects; furthermore, the effects of treatment may manifest in higher or lower activity counts or in subtler ways like changes in the frequency of certain types of activities. We use a zero inflated Poisson hidden semi-Markov model to characterize activity patterns and subsequently derive estimators of the treatment effect in terms of changes in activity levels or frequency of activity type. We demonstrate the application of our model, and its advance over traditional analysis methods, using data from a naturally occurring feline OA-associated pain model.
Evaluation of carboxyfluorescein-labeled 7-methylguanine nucleotides as probes for studying cap-binding proteins by fluorescence anisotropy
Authors: Wojtczak Anna , Kasprzyk Renata , Warmiński Marcin , Ubych Krystian , Kubacka Dorota , Sikorski Pawel J. , Jemielity Jacek , Kowalska Joanna
Published: April 2021

Fluorescence anisotropy (FA) is a powerful technique for the discovery of protein inhibitors in a high-throughput manner. In this study, we sought to develop new universal FA-based assays for the evaluation of compounds targeting mRNA 5′ cap-binding proteins of therapeutic interest, including eukaryotic translation initiation factor 4E and scavenger decapping enzyme. For this purpose, a library of 19 carboxyfluorescein probes based on 7-methylguanine nucleotides was evaluated as FA probes for these proteins. Optimal probe:protein systems were further investigated in competitive binding experiments and adapted for high-throughput screening. Using a small in-house library of compounds, we verified and confirmed the accuracy of the developed FA assay to study cap-binding protein binders. The applications of the most promising probes were then extended to include evaluation of allosteric inhibitors as well as RNA ligands. From this analysis, we confirmed the utility of the method to study small molecule ligands and evaluate differently 5′ capped RNAs.
Fragmented sleep relates to hallucinations across perceptual modalities in the general population
Authors: Brederoo Sanne G. , de Boer Janna N. , de Vries Jacqueline , Linszen Mascha M. J. , Sommer Iris E. C.
Published: April 2021

Although previous studies reported a link between sleep problems and the occurrence of hallucinations, more detailed information is needed to translate this association into clinical practice. This study investigates sleep quality and its relation to prevalence, type, content, and phenomenology of hallucinations, using an online survey in a large population sample (n = 10,299). Based on community-based cluster analysis, four groups could be distinguished that differed in terms of sleep quality. Our results confirm previous studies in showing that poor sleep is associated with the occurrence of hallucinations, and extend previous results on a number of aspects. First, we show that particularly fragmented sleep relates to the occurrence of hallucinations. Second, we show that this is the case for hallucinations across the auditory, visual, olfactory, and tactile domains. Third, our results show that fragmented sleep not only relates to the occurrence, but also to the content, frequency, duration, and associated distress of hallucinations. Finally, compared to poor sleep, good sleep quality is associated with hallucinations that are less negative and disruptive. We conclude that sleep hygiene measures could have a large positive impact on individuals whose fragmented sleep underlies the occurrence of bothersome hallucinations.
Using mounting, orientation, and design to improve bat box thermodynamics in a northern temperate environment
Authors: Fontaine Amélie , Simard Anouk , Dubois Bryan , Dutel Julien , Elliott Kyle H.
Published: April 2021

Wildlife managers design artificial structures, such as bird houses and bat boxes, to provide alternative nesting and roosting sites that aid wildlife conservation. However, artificial structures for wildlife may not be equally efficient at all sites due to varying climate or habitat characteristics influencing thermal properties. For example, bat boxes are a popular measure employed to provide compensatory or supplementary roost sites for bats and educate the public. Yet, bat boxes are often thermally unstable or too cold to fulfill reproductive females needs in northern temperate environments. To help improve the thermodynamics of bat boxes, we tested the effect of (1) three mountings, (2) four orientations, and (3) twelve bat box designs on the internal temperature of bat boxes. We recorded temperatures in bat boxes across a climate gradient at seven sites in Quebec, Canada. Bat boxes mounted on buildings had warmer microclimates at night than those on poles and those facing east warmed sooner in the morning than those facing west or south. Our best new model based on passive solar architecture (Ncube PH1) increased the time in the optimal temperature range (22–40 °C) of targeted species by up to 13% compared to the most commonly used model (Classic 4-chamber) when mounted on a building with an east orientation (other designs presented in the Supplementary Information). Based on bioenergetic models, we estimated that bats saved up to 8% of their daily energy using the Ncube PH1 compared to the Classic 4-chamber when mounted on a building with an east orientation. We demonstrate that the use of energy-saving concepts from architecture can improve the thermal performance of bat boxes and potentially other wildlife structures as well.