bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-human demonstration of floating EMG sensors and stimulators wirelessly powered and operated by volume conduction
Authors: Becerra-Fajardo Laura , Minguillon Jesus , Krob Marc Oliver , Rodrigues Camila , Sánchez Miguel González- , Megía-García Álvaro , Galán Carolina Redondo , Henares Francisco Gutiérrez , Comerma Albert , del-Ama Antonio J. , Gil-Agudo Angel , Grandas Francisco , Schneider-Ickert Andreas , Barroso Filipe Oliveira , Ivorra Antoni 
Published: July 2023

AbstractBackgroundRecently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation.MethodsA proof-of-concept device, consisting of implantable thin-film electrodes and a non-implantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant.ResultsFour devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device.ConclusionsThis is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.
Non-invasive modulation of the human dorsal anterior cingulate attenuates acute pain perception and homeostatic cardiovascular responses
Authors: Strohman Andrew , Payne Brighton , In Alexander , Stebbins Katelyn , Legon Wynn 
Published: July 2023

ABSTRACTHomeostasis is the process of maintaining physiologic balance in the body that is critical for maintaining health and is dysfunctional in several disorders like chronic pain. The dorsal anterior cingulate cortex (dACC) is a critical brain area for homeostatic cardiovascular responses and pain processing, making it a promising non-invasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to non-invasively modulate the dACC for an effect on behavioral and cardiac autonomic responses using a transient heat pain stimulus. N = 16 healthy human volunteers (6M/10F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included perceived pain ratings, homeostatic measures including heart-rate variability, blood pressure, EDR response as well as the amplitude of the contact heat-evoked potential (CHEP).LIFU reduced pain ratings by 1.08 ± 0.21 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on blood pressure or EDR. LIFU resulted in a 25.1% reduction in the N1-P1 CHEP amplitude driven primarily by effects on the P1 amplitude. Our results demonstrate LIFU to the dACC reduces perceived pain and alters homeostatic cardiovascular responses to a transient heat pain stimulus. These results have implications for the causal understanding of human pain and autonomic processing in the dACC and the potential for future therapeutics for pain relief and homeostatic modulation.SIGNIFICANCE STATEMENTNew lines of inquiry now demonstrate cardiac homeostatic signals like heart rate variability (HRV) are aberrant in mental health disorders, addiction, and chronic pain and may contribute to their underlying etiology. The dorsal anterior cingulate cortex (dACC) is a key homeostatic center with direct influences on cardiovascular autonomic function, but its depth precludes direct access without invasive surgery. For the first time in humans, we demonstrate low-intensity focused ultrasound (LIFU) can non-invasively and selectively modulate the dACC to reduce acute pain perception and homeostatic cardiovascular responses as well as pain processing signals. This work helps establish a causal role of the dACC in pain perception and homeostatic signaling with potential future clinical applications in chronic pain and neuropsychological populations.
Both systemic Calcitonin Gene Related Peptide (CGRP) and a vestibular challenge promote anxiety-related behaviors and dynamic imbalance in mice
Authors: Rahman Shafaqat M. , Hauser Catherine , Faucher Stefanie , Fine Elana , Luebke Anne E. 
Published: July 2023

AbstractMotion-induced anxiety and agoraphobia are more frequent symptoms in patients with vestibular migraine than migraine without vertigo. The neuropeptide calcitonin gene-related peptide (CGRP) is a therapeutic target for migraine and vestibular migraine, but the link between motion hypersensitivity, anxiety, and CGRP is relatively unexplored, especially in preclinical mouse models. To further examine this link, we tested the effects of systemic CGRP and off-vertical axis rotation (OVAR) on elevated plus maze (EPM) and rotarod performance in male and female C57BL/6J mice. Rotarod ability was assessed using two different dowel diameters: mouse dowel (r = 1.5 cm) versus rat dowel (r = 3.5 cm). EPM results indicate CGRP increased anxiety indexes and time spent in the closed arms in females but not males, while OVAR increased anxiety indexes and time spent in the closed arms in both sexes. The combination of CGRP and OVAR elicited even greater anxiety-like behavior. On the rotarod, CGRP reduced performance in both sexes on a mouse dowel but had no effect on a rat dowel, whereas OVAR had a significant effect on the rat dowel. Rotarod performance is influenced by dowel diameter, with larger dowels presenting greater challenges on balance function. These results suggest that both CGRP and vestibular stimulation induce anxiety-like behavior and that CGRP affects dynamic balance function in mice depending on the type of challenge presented. Findings highlight the potential translation of anti-CGRP receptor signaling therapeutics for treating motion hypersensitivity and motion-induced anxiety that manifests in vestibular migraine.Significance statementAnxiety is very common in patients with dizziness and vestibular migraine (VM). Elevated CGRP levels have been linked to migraine symptoms of increased light and touch sensitivity in mice and humans and we wondered if a systemic injection of CGRP into mice would increase anxiety and imbalance; and if mice further exposed to a vestibular stimulus would have their anxiety measures sharpened. We observed a female preponderance in both CGRP and motion-induced anxiety-like behaviors, suggesting that the role of CGRP in migraine’s anxiety symptoms can be recapitulated in the mouse. Our findings suggest that CGRP signaling has a pertinent role in motion-induced anxiety and dynamic imbalance, and warrants the potential use of anti-CGRP therapies for the treatment of these symptoms.
Antigenic cartography using variant-specific hamster sera reveals substantial antigenic variation among Omicron subvariants
Authors: Mühlemann Barbara , Trimpert Jakob , Walper Felix , Schmidt Marie L. , Schroeder Simon , Jeworowski Lara M. , Beheim-Schwarzbach Jörn , Bleicker Tobias , Niemeyer Daniela , Adler Julia M. , Vidal Ricardo Martin , Langner Christine , Vladimirova Daria , Smith Derek J. , Voß Mathias , Paltzow Lea , Martínez Christophersen Christina , Rose Ruben , Krumbholz Andi , Jones Terry C. , Corman Victor M. , Drosten Christian 
Published: July 2023

AbstractSARS-CoV-2 has developed substantial antigenic variability. As the majority of the population now has pre-existing immunity due to infection or vaccination, the use of experimentally generated animal immune sera can be valuable for measuring antigenic differences between virus variants. Here, we immunized Syrian hamsters by two successive infections with one of eight SARS-CoV-2 variants. Their sera were titrated against 14 SARS-CoV-2 variants and the resulting titers visualized using antigenic cartography. The antigenic map shows a condensed cluster containing all pre-Omicron variants (D614G, Alpha, Delta, Beta, Mu, and an engineered B.1+E484K variant), and a considerably more distributed positioning among a selected panel of Omicron subvariants (BA.1, BA.2, BA.4/5, the BA.5 descendants BF.7 and BQ.1.18; the BA.2.75 descendant BN.1.3.1; and the BA.2-derived recombinant XBB.2). Some Omicron subvariants were as antigenically distinct from each other as the wildtype is from the Omicron BA.1 variant. The results highlight the potential of using variant-specifically infected hamster sera for the continued antigenic characterisation of SARS-CoV-2.
Lack of detection of SARS-CoV-2 in Wildlife from Kerala, India in 2020-21
Authors: Zachariah Arun , Krishnankutty Sajesh P , Manazhi Jishnu , Omanakuttan Vishnu , Santhosh Sam , Blanchard Adam , Tarlinton Rachael 
Published: July 2023

2.AbstractSpill over of SARs-CoV-2 into a variety of wild and domestic animals has been an ongoing feature of the human pandemic. The establishment of a new reservoir in white tailed deer in North America and increasing divergence of the viruses circulating in them from those circulating in the human population has highlighted the ongoing risk this poses for global health. Some parts of the world have seen more intensive monitoring of wildlife species for SARS-CoV-2 and related coronaviruses but there are still very large gaps in geographical and species-specific information. This paper reports negative results for SARS-CoV-2 PCR based testing using a pan coronavirus end point RDRP PCR and a Sarbecovirus specific E gene qPCR on lung and or gut tissue from wildlife from the Indian State of Kerala. These animals included: 121Rhinolophus rouxii(Rufous Horsehoe Bat),6 Rhinolophus bedommei(Lesser Woolly Horseshoe Bat),15 Rossettus leschenaultii(Fulvous Fruit Bat),47 Macaca radiata(Bonnet macaques),35 Paradoxurus hermaphroditus (Common Palm Civet),5 Viverricula indica(Small Indian Civet),4 Herpestes edwardsii(Common Mongoose),10 Panthera tigris(Bengal Tiger),8 Panthera pardus fusca(Indian Leopard), 4Prionailurus bengalensis(Leopard cats), 2Felis chaus(Jungle cats), 2Cuon alpinus(Wild dogs) and 1Melursus ursinus(sloth bear).
Mechanism of branching morphogenesis inspired by diatom silica formation
Authors: Babenko Iaroslav , Kröger Nils , Friedrich Benjamin M. 
Published: July 2023

AbstractThe silica-based cell walls of diatoms are prime examples of genetically controlled, species-specific mineral architectures. The physical principles underlying morphogenesis of their hierarchically structured silica patterns are not understood, yet such insight could indicate novel routes towards synthesizing functional inorganic materials. Recent advances in imaging nascent diatom silica allow rationalizing possible mechanisms of their pattern formation. Here, we combine theory and experiments on the model diatomThalassiosira pseudonanato put forward a minimal model of branched rib patterns – a fundamental feature of the silica cell wall. We quantitatively recapitulate the time-course of rib pattern morphogenesis by accounting for silica biochemistry with autocatalytic formation of diffusible silica precursors followed by conversion into solid silica. We propose that silica deposition releases an inhibitor that slows down up-stream precursor conversion, thereby implementing a self-replicating reaction-diffusion system featuring a non-classical Turing mechanism. The proposed mechanism highlights the role of geometrical cues for guided self-organization, rationalizing the instructive role for the single initial pattern seed known as primary silicification site. The mechanism of branching morphogenesis that we characterize here is possibly generic and may apply also in other biological systems.Significance statementThe formation of minerals by living organisms is a widespread biological phenomenon occurring throughout the evolutionary tree-of-life. The silica-based cell walls of diatom microalgae are impressive examples featuring intricate architectures and outstanding materials properties that still defy their reconstitutionin vitro. Here, we developed a minimal mathematical model that explains the formation of branched patterns of silica ribs, providing unprecedented understanding of basic physico-chemical processes capable of guiding silica morphogenesis in diatoms. The generic mechanism of branching morphogenesis identified here could provide recipes for bottom-up synthesis of mineral-nanowire networks for technological applications. Moreover, similar mechanisms may apply in the biological morphogenesis of other branched structures, like corals, bacterial colonies, tracheal networks, fungal plexuses, or the vascular system.
Solute Transport in Engineered Living Materials using Bone Inspired Microscale Channel Networks
Authors: van Wijngaarden Ellen W. , Bratcher Samantha , Lewis Karl J. , Hernandez Christopher J. 
Published: July 2023

AbstractEngineered living materials (ELMs) are an emerging class of materials that is synthesized and/or populated by living cells. Maintaining living cells within an ELM over prolonged periods remains a major technical challenge that limits the service life of a material. Biological materials regularly maintain robust populations of living cells. Bone maintains living cells for decades by delivering nutrients through a network of nanoscale channels punctuated by microscale pores. Nutrient transfer in bone is enabled by mechanical loading experienced during regular use. Here we identify the characteristics of channel-pore network geometries and external mechanical loading that can be used in engineered living materials to deliver nutrients to resident cell populations. Transport occurs when deformation in the microscale pore network exceeds the volume of the connecting channels. Computational models show that transport is enhanced at greater load magnitudes and lower loading frequencies and are consistent with experimental validation using microfluidic systems. Our findings provide quantitative design principles for channel-pore networks capable of delivering nutrients to materials designed to house living cells.
Effect of Aging on the Human Myometrium at Single-Cell Resolution
Authors: Punzón-Jiménez P , Machado-Lopez A , Pérez-Moraga R , Llera-Oyola J , Grases D , Galvez-Viedma M , AlSibai M , Satorres E , Badenes R , Ferrer C , Porta-Pardo E , Roson B , Simón C , Mas A 
Published: July 2023

AbstractThe myometrial dysfunction associated with aging can prompt complications during pregnancy and labor, causing a 7.8-fold increase in maternal mortality in women over 40. Using single-cell/single-nucleus RNA sequencing and spatial transcriptomics, we constructed a cellular atlas of the aging myometrium from 186,120 cells across twenty peri- and post-menopausal women. We identified 23 myometrial cell subpopulations, including novel contractile capillary, venous capillary, immune-modulated fibroblasts, and nervous system regulatory fibroblasts. Myometrial aging leads to fewer contractile capillary cells, a reduced level of ion channel expression in smooth muscle cells, and impaired gene expression in endothelial, smooth muscle, fibroblast, perivascular, and immune cells. We observed altered myometrial cell-to-cell communication as an aging hallmark associated with the loss of 25/229 signaling pathways, including those related to angiogenesis, tissue repair, contractility, immunity, and nervous system regulation. These insights may contribute to a better understanding of the complications faced by older women during pregnancy and labor.
Unraveling the Interplay of Different Traits and Parameters Related to Nitrogen Use Efficiency in Wheat: Insights for Grain Yield Influence
Authors: Gayatri  , Mandal Puja , Venkatesh Karnam , Mandal Pranab Kumar 
Published: July 2023

AbstractEnhancing Nitrogen Use Efficiency (NUE) in wheat to optimize grain yield is a significant challenge. To address this challenge, a comprehensive study was conducted to investigate various morphological, biochemical, molecular parameters, and agronomic traits related to NUE. By examining various traits under both optimum-N (ON) and stressed-N (SN) conditions, the study explores the interrelationships among these traits, providing novel insights not previously reported. A set of 278 diverse wheat genotypes were assessed, encompassing eight NUE-related traits: Grain Yield, Biomass, Grain nitrogen, N at head, N at harvest, N-uptake, Nitrogen Uptake Efficiency, Nitrogen Utilization Efficiency, and NUE under both ON and SN conditions in the field. The findings demonstrated a significant positive correlation between grain yield and all NUE-related traits, highlighting their significance in comprehending the biological NUE of wheat plants. Notably, the study identified N-uptake and N-uptake related traits as key factors influencing the impact of soil nitrogen status on yield and associated parameters. These traits hold particular importance for selecting wheat genotypes with optimal yield and NUE in wheat cultivation. To complement the field data, representative genotypes were further subjected to a hydroponics experiment under absolute nitrogen control. This experiment provided insights into the effects of nitrogen stress on morphological parameters and the performance of eight essential nitrogen and carbon metabolizing enzymes. Correlation analysis highlighted the substantial influence of four key N-metabolizing enzymes, namely Nitrate Reductase, Glutamine Synthetase, Glutamate Oxo-Glutarate Amino Transferase, and Glutamate Dehydrogenase, on grain yield. Additionally, this study underscored the direct and indirect associations between seedling parameters and field traits, emphasizing the significance of shoot and root length parameters in nitrogen acquisition under nitrogen stress. In conclusion, these findings offer valuable insights into the intricate network of traits and parameters that influence wheat grain yield under varying nitrogen regimes. This knowledge can aid in the selection of wheat genotypes with enhanced NUE and grain yield, particularly in scenarios of reduced nitrogen application.Key PointsA comprehensive study in field and hydroponics conditions revealed differential responses of various morphological, biochemical, molecular parameters, and agronomic traits to different nitrogen levels.N-uptake related traits in field condition and chlorophyll content and morphological parameters in hydroponics condition were found as essential factors contributing to variations under both optimum and stressed N conditions.Among the parameters observed in the seedling stage, SL and RL, along with the enzymes NR, GS, GOGAT, and GDH, demonstrated their influence on GY.
Incorporating slow NMDA-type receptors with nonlinear voltage-dependent magnesium block in a next generation neural mass model: derivation and dynamics
Authors: Sheheitli Hiba , Jirsa Viktor 
Published: July 2023

AbstractWe derive a next generation neural mass model of a population of quadratic-integrate-and-fire neurons, with slow adaptation, and conductance-based AMPAR, GABAR and nonlinear NMDAR synapses. We show that the Lorentzian ansatz assumption can be satisfied by introducing a piece-wise polynomial approximation of the nonlinear voltage-dependent magnesium block of NMDAR current. We study the dynamics of the resulting system for two example cases of excitatory cortical neurons and inhibitory striatal neurons. Bifurcation diagrams are presented comparing the different dynamical regimes as compared to the case of linear NMDAR currents, along with sample comparison simulation time series demonstrating different possible oscillatory solutions. The omission of the nonlinearity of NMDAR currents results in a shift in the range (and possible disappearance) of the constant high firing rate regime, along with a modulation in the amplitude and frequency power spectrum of oscillations. Moreover, nonlinear NMDAR action is seen to be state-dependent and can have opposite effects depending on the type of neurons involved and the level of input firing rate received. The presented model can serve as a computationally efficient building block in whole brain network models for investigating the differential modulation of different types of synapses under neuromodulatory influence or receptor specific malfunction.Statements and DeclarationsThe authors have no competing interests to declare.FundingWe acknowledge support by H2020 Research and Innovation Action grants Human Brain Project SGA3 number 945539.
Efficient inference of large pangenomes with PanTA
Authors: Le Duc Quang , Nguyen Tien Anh , Nguyen Son Hoang , Nguyen Tam Thi , Nguyen Canh Hao , Phung Huong Thanh , Ho Tho Huu , Vo Nam S. , Nguyen Trang , Nguyen Hoang Anh , Cao Minh Duc 
Published: July 2023

AbstractPangenome analysis is an indispensable step in bacterial genomics to address the high variability of bacteria genomes. However, speed and scalability remain a challenge for pangenome inference software tools to cope with the fast-growing genomic collections. We present PanTA, a software package for constructing the pangenomes of large bacterial collections. We show that PanTA exhibits an unprecedented multiple times more efficient than the current state-of-the-arts while maintaining a similar pangenome accuracy. In addition, PanTA introduces a novel mechanism to construct the pangenome progressively where new samples are added into an existing pangenome without rebuilding the accumulated collection from scratch. In the progressive mode, PanTA is demonstrated to consume orders of magnitude less computational resource than existing solutions in managing the pangenomes of growing microbial datasets. We further show that PanTA can build the pangenome of the entire collection of >28000Escherichia coligenomes from the RefSeq database on a laptop computer in 32 hours, highlighting the scalability and practicality of PanTA.The software is open source and is publicly available athttps://github.com/amromics/pantaunder an MIT license.