bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose-Response in Modulating Brain Function with Transcranial Direct Current Stimulation: From Local to Network Levels
Authors: Soleimani Ghazaleh , Kupliki Rayus , Paulus Martin , Ekhtiari Hamed
Published: November 2022

Background

Non-invasive brain stimulation methods for modulating brain activity via transcranial technologies like transcranial direct current stimulation (tDCS) are increasingly prevalent to investigate the relationship between modulated brain regions and stimulation outcomes. However, the inter-individual variability of tDCS has made it challenging to detect intervention effects at the group level. Collecting multiple modalities of magnetic resonance imaging data (i.e., structural and functional MRI) helps to investigate how dose-response ultimately shapes brain function in response to tDCS.

Method

We collected data in a randomized, triple-blind, sham-controlled trial with two parallel arms. Sixty participants with MUD were randomly assigned to sham or active tDCS (n=30 per group, 2 mA, 20 minutes, anode/cathode over F4/Fp1). Structural and functional MRI (including high-resolution T1 and T2-weighted MRI, resting-state fMRI, and methamphetamine cue-reactivity task with meth versus neutral cues) were collected immediately before and after tDCS. T1 and T2-weighted MRI data were used to generate head models for each individual to simulate electric fields. Associations between electric fields (dose) and changes in brain function (response) were investigated at four different levels: (1) voxel level, (2) regional level (atlas-based parcellation), (3) cluster level (active clusters in the contrast of interest), and (4) network level (both task-based and resting-state networks).

Result

At the (1) voxel-level, (2) regional level, and (3) cluster level, our results showed no significant correlation between changes in the functional activity and electric fields. However, (4) at the network level, a significant negative correlation was found between the electric field and ReHo in the default mode network (r=-0.46 (medium effect size), p corrected=0.018). For the network-level analysis of task-based fMRI data, frontoparietal connectivity showed a positive significant correlation with the electric field in the frontal stimulation site (r=0.41 (medium effect size), p corrected=0.03).

Conclusion

The proposed pipeline provides a methodological framework to analyze tDCS effects in terms of dose-response relationships at four different levels to directly link the electric field (dose) variability to the variability of the neural response to tDCS. The results suggest that network-based analysis might be a better approach to provide novel insights into the dependency of the neuromodulatory effects of tDCS on the brain’s regional current dose in each individual. Dose-response integration can be informative for dose optimization/customization or predictive/treatment-response biomarker extraction in future brain stimulation studies.
Incidence of perioperative anaphylaxis in 2021 in Japan: Survey of 34 hospitals of Social Welfare Organization Saiseikai Imperial Gift Foundation, Inc
Authors: Suzuki Yasuyuki , Liu Shuang , Yamashita Natsumi , Yamaguchi Naohito , Takasaki Yasushi , Yorozuya Toshihiro , Mogi Masaki
Published: November 2022

Perioperative anaphylaxis (POA) is a severe complication with a low incidence and diverse risk factors. Its low incidence makes a detailed survey of POA challenging. Recent large-scale surveys in Japan have focused on identifying the causative agents using the basophil activation test. Only facilities, such as university hospitals, that can dispatch samples for this test participate, which may introduce bias. We surveyed the incidence of POA primarily in secondary hospitals, such as the Saiseikai hospitals, throughout Japan.

We targeted data collection for the year 2021. Thirty-five facilities answered (Supplementary 1, 2); we excluded 1 reporting no surgeries. In total, 70,523 surgeries were performed, with POA diagnosed in 7 cases. For diagnosis, the skin test was used in 3 cases and quantification of histamine and tryptase in 1 case. In 3 cases, diagnosis was based on the time to onset of POA after drug use. Multiple tests are important to ensure patient safety. However, in this survey, no hospital performed in vitro tests to identify the cause. This is major limitation, however, as many hospitals do not have experimental laboratories, we believe that this study, which focuses on secondary care institutions, contributes to the literature significantly by presenting the current situation in clinical practice.
A Novel Use of a Tissue Oxygenation Monitor at Time of Uterus Transplantation and Hysterectomy – A Feasibility Study
Authors: Applebaum Jeremy , Zhao Dan , Barry Dan , Latif Nawar , O’Neill Kathleen
Published: November 2022

While thrombosis is the most common indication for graft failure and immediate hysterectomy of a transplanted uterus, there is no optimal method to monitor graft perfusion. In this feasibility study, a near-infrared spectroscopy probe that monitors local tissue oxygenation (StO2) was attached to four uterine cervices and three donor cervices at the time of hysterectomy and transplantation respectively. Real-time StO2measurements were gathered at key surgical steps of the hysterectomies and uterus transplantations. The average StO2for the sequential steps of a hysterectomy of baseline, ovarian vessel ligation, contralateral ovarian vessel ligation, uterine vessel ligation, contralateral uterine vessel ligation, and colpotomy was 70.2%, 56.7%, 62.1%, 50.5%, 35.8%, and 8.5% respectively. The average StO2for the sequential steps of uterus transplantation of iliac vein anastomosis, iliac artery anastomosis, contralateral iliac vein anastomosis, contralateral iliac artery anastomosis, and vaginal anastomosis was 8.9%, 27.9%, 56.9%, 65.9%, and 65.2% respectively. As uterine blood supply decreases in a hysterectomy, the measured StO2also decreases, and vice versa for uterus transplantation. Tissue oximetry may be a reliable, non-invasive means of monitoring perfusion of a uterine graft. Additional studies are needed to determine if these devices complement current assessments of uterine graft viability and salvage thrombosed grafts.
White matter tract integrity is reduced in major depression and in individuals with genetic liability for depression
Authors: Nothdurfter David , Jawinski Philippe , Markett Sebastian
Published: November 2022

0.

Major depression has been linked to alterations of the brain’s white matter architecture. Major depression has also a considerable genetic component. It is, however, unclear if genetic liability for depression relates directly to the suggested alterations at the brain level.

We re-evaluated white matter fiber tract alterations in major depression and aimed to relate polygenic risk for depression in unaffected individuals to these alterations.

We conducted a population-based retrospective cohort study with N=17183 participants (n=287 currently depressed, n=5536 formerly depressed, n= 13360 healthy) aged 44 to 82 from the UK Biobank imaging cohort, collected between 2015 and 2020.

Depression status was assessed based on questionnaire data. We derived 27 major white matter tracts from diffusion MRI and indexed their integrity according to mean fractional anisotropy. Genetic liability for depression was quantified by polygenic scores based on three recent case-control GWAS.

White matter integrity was globally reduced in depression. The reduction was most pronounced on thalamic and intracortical fiber tracts, where the reduction was observed irrespective of current symptom status. Non-depressed individuals showed already a reduction in relevant fiber tracts with increasing polygenic risk, particularly in thalamic radiations. Subsequent in-silico simulations and non-parametric tests confirmed that the polygenic association was stronger than expected given the low-level statistical dependencies between target and discovery samples. White matter integrity on thalamic and association tracts is reduced in depression irrespective of current disease status and relates to the underlying genetic risk factors in unaffected individuals. The observed statistical links between genes, brain, and disorder adhere to the definition of an intermediate phenotype at the brain level.
Artificial intelligence and MRI: the source of a new epilepsy taxonomy
Authors: Xiao Fenglai , Caciagli Lorenzo , Wandschneider Britta , Sone Daichi , Young Alexandra L. , Vos Sjoerd B. , Winston Gavin P. , Zhang Yingying , Liu Wenyu , An Dongmei , Kanber Baris , Zhou Dong , Sander Josemir W. , Duncan John S. , Alexander Daniel C. , Galovic Marian , Koepp Matthias J.
Published: November 2022

Artificial intelligence (AI)-based tools are widely employed, but their use for diagnosis and prognosis of neurological disorders is still evolving. We capitalise on a large-scale, cross-sectional structural MRI dataset of 814 people with epilepsy. We use a recently developed machine-learning algorithm, Subtype and Stage Inference (SuStaIn), to develop a novel data-driven disease taxonomy based on distinct patterns of spatiotemporal progression of brain atrophy. We identify two subtypes common to focal and idiopathic generalised epilepsies, characterised by neocortical-driven or basal ganglia-driven progression, and a third subtype, only detected in focal epilepsies, characterised by hippocampus-driven progression. We corroborate external validity via an independent cohort of 254 people and decode associations between progression subtypes and clinical measures of epilepsy severity. Our findings suggest fundamental processes underlying the progression of epilepsy-related brain atrophy. We deliver a novel MRI- and AI-guided epilepsy taxonomy, which could be used for individualised prognostics and targeted therapeutics.
Decoding Motor Plans Using a Closed-Loop Ultrasonic Brain-Machine Interface
Authors: Griggs Whitney S. , Norman Sumner L. , Deffieux Thomas , Segura Florian , Osmanski Bruno-Félix , Chau Geeling , Christopoulos Vasileios , Liu Charles , Tanter Mickael , Shapiro Mikhail G. , Andersen Richard A.
Published: November 2022

Brain-machine interfaces (BMIs) can be transformative for people living with chronic paralysis. BMIs translate brain signals into computer commands, bypassing neurological impairments and enabling people with neurological injury or disease to control computers, robots, and more with nothing but thought. State-of-the-art BMIs have already made this future a reality in limited clinical trials. However, high performance BMIs currently require highly invasive electrodes in the brain. Device degradation limits longevity to about 5 years. Their field of view is small, restricting the number, and type, of applications possible. The next generation of BMI technology should include being longer lasting, less invasive, and scalable to sense activity from large regions of the brain. Functional ultrasound neuroimaging is a recently developed technique that meets these criteria. In this present study, we demonstrate the first online, closed-loop ultrasonic brain-machine interface. We used 2 Hz real-time functional ultrasound to measure the neurovascular activity of the posterior parietal cortex in two nonhuman primates (NHPs) as they performed memory-guided movements. We streamed neural signals into a classifier to predict the intended movement direction. These predictions controlled a behavioral task in real-time while the NHP did not produce overt movements. Both NHPs quickly succeeded in controlling up to eight independent directions using the BMI. Furthermore, we present a simple method to “pretrain” the BMI using data from previous sessions. This enables the BMI to work immediately from the start of a session without acquiring extensive additional training data. This work establishes, for the first time, the feasibility of an ultrasonic BMI and prepares for future work on a next generation of minimally invasive BMIs that can restore function to patients with neurological, physical, or even psychiatric impairments.
X-inactivation states of single cell transcriptomes reveal cellular phylogenies in human females
Authors: Predeus Alexander , Arutyunyan Anna , Jardine Laura , Suo Chenqu , Dann Emma , Hoo Regina , Prete Martin , Haniffa Muzlifah , Mitchell Thomas J. , Vento-Tormo Roser , Young Matthew D.
Published: November 2022

Human females undergo X-inactivation (Xi), whereby one copy of X is randomly inactivated early in development, then propagated through cell division. Because Xi state is inherited, its measurement in populations of cells encodes information about the phylogeny that created them and their relationships to other cells. We present a method, inactiveXX, to determine the Xi state of single cell transcriptomes, and demonstrate its accuracy using cancer and gold standard reference data. We apply inactiveXX to single cell transcriptomes from 190 human females, revealing that Xi in humans likely occurs around the 16 cell blastocyst stage and affects both embryonic and extra-embryonic tissues. We further find significant cell type specific variability in Xi skew, only detectable with cell type specific resolution, with certain cell types exhibiting strong population bottlenecks across tissues and disease state.
GlyLES: Grammar-based Parsing of Glycans from IUPAC-condensed to SMILES
Authors: Joeres Roman , Bojar Daniel , Kalinina Olga V.
Published: November 2022

Glycans are important polysaccharides on cellular surfaces that are bound to glycoproteins and glycolipids. These are one of the most common post-translational modifications of proteins in eukaryotic cells. They play important roles in protein folding, cell-cell interactions, and other extracellular processes. Changes in glycan structures may influence the course of different diseases, such as infections or cancer.

Glycans are commonly represented using the IUPAC-condensed notation. IUPAC-condensed is a textual representation of the Symbol Nomenclature for Glycans (SNFG) that assigns a colored, geometrical shape to the main monosaccharides. These symbols are then connected in tree-like structures, visualizing the glycan structure on a polymeric level. Yet for a representation on the atomic level, notations such as SMILES should be used. To our knowledge, there is no easy-to-use, general, open-source, and offline tool to convert the IUPAC-condensed notation to SMILES. Here, we present the open-access Python package GlyLES for the generalizable generation of SMILES representations out of IUPAC-condensed representations. GlyLES uses a grammar to read in the monomer tree from the IUPAC-condensed notation. From this tree, the tool can compute atomic structures of each monomer based on their IUPAC-condensed descriptions. In the last step, it merges all monomers into the atomic structure of a glycan in the SMILES notation.

GlyLES is the first package that allows conversion between IUPAC-condensed notations of glycans and SMILES strings. This may have multiple applications, including straightforward visualization, substructure search, molecular modelling and docking, and a new featurization strategy for machine-learning algorithms. GlyLES is available athttps://github.com/kalininalab/GlyLES.
Slower, but deeper community change: anthropogenic impacts on species temporal turnover are regulated by intrinsic dynamics
Authors: Terry J. Christopher D. , Rossberg Axel G.
Published: November 2022

Understanding the mechanisms behind biodiversity is central to assessing and forecasting anthropogenic impacts on ecological communities. However, quite how intrinsic ecological processes and external environmental drivers act together in natural systems to influence local temporal turnover is currently largely unexplored. Here, we determine how human impacts affect multiple metrics of bird community turnover to establish the ecological mechanisms behind compositional change. We used US Breeding Bird Survey data to calculate transect-level rates of three measures of temporal species turnover: a) short-term (initial rate of decline of Sørensen similarity), b) long-term (asymptotic Sørensen similarity), and c) overall species accumulation rate (species-time relationship exponents) over 2692 transects across 27 habitat types. We then hierarchically fit linear models to estimate the effect on these turnover metrics of anthropogenic impact via the Human Modification Index proxy, while accounting for observed species richness, the size of the species pool and annual environmental variability. We found broadly consistent impacts of increased anthropogenic pressures across diverse habitat types. The Human Modification Index was associated with greater turnover at long-timescales, but marginally slower short-term turnover. The species accumulation rate through time was not notably influenced. Examining anthropogenic impacts on different aspects of species turnover in combination allows greater ecological insight. Observed human impacts on short-term turnover were the opposite of existing expectations and suggest humans are disrupting the background turnover of these systems, rather than simply driving rapid directed turnover. The increased long-term turnover was driven by more frequent species changes between core and occasional status rather than greater arrival of ‘new’ species. These results highlight the role of intrinsic dynamics and caution against simple interpretations of increased species turnover as reflections of environmental change.

Open Research Statement

No new empirical data are used in the manuscript as all primary data is publicly available, as cited in the manuscript. Our code repository (including fitted model objects and markdown documents detailing all steps) is available athttps://figshare.com/s/f5b9152ff7643efb347d.
Grip-preference distribution among Asian-Oceanian floorball players is opposite that of European and North American players – How environmental constraints may influence human motor behaviour
Authors: Ekman Karen Emilia , Pedersen Arve Vorland
Published: November 2022

Whilst most humans are right-handed, handedness alone cannot explain the large variability observed in bimanual motor behaviour. Sport-specific motor behaviour provides a natural laboratory for laterality and motor-control research. It is common knowledge that, in floorball, European players more often play using a left-sided grip, whereas most Asian players are right-gripped, with no logical explanation. However, the exact grip-side distribution is unknown. The present study investigated the influence of environmental constraints on lateral motor behaviour by assessing geographic variabilities in floorball-specific grip preferences between European and Asian national team floorball players. A small-scale Big Data approach was utilised to collect data on lateral preferences for both field players and goalkeepers from the International Floorball Federation website. In all, data for 2,935 players representing 40 national teams from three different confederations (Europe, Asia-Oceania, and North America) were included. More than two-thirds of European and North American players preferred a left-sided grip, whereas the same number of Asian-Oceanian players preferred a right-sided grip. To the best of our knowledge, these are the first findings of such large geographic variations in any lateralised motor behaviour. No biological factors are likely responsible for the difference in lateral-preference distribution. Environmental and task-specific constraints are discussed as possible explanations.
Cholinergic-estrogen interaction underpins the effect of education on attenuating cognitive sex differences in a Thai healthy population
Authors: Chen Chen , Khanthiyong Bupachad , Charoenlappanit Sawanya , Roytrakul Sittiruk , Thanoi Samur , Nudmamud-Thanoi Sutisa
Published: November 2022

The development of human brain is shaped by both genetic and environmental factors. Sex differences in cognitive function have been found in humans as a result of sexual dimorphism in neural information transmission. Numerous studies have reported the positive effects of education on cognitive functions. However, little work has investigated the effect of education on attenuating cognitive sex differences and the neural mechanisms behind it based on healthy population. In this study, the Wisconsin Card Sorting Test (WCST) was employed to examine sex differences in cognitive function in 135 Thai healthy subjects, and label-free proteomic method and bioinformatic analysis were used to study sex-specific neurotransmission-related protein expression profiles. The results showed a sex difference in two WCST subscores: percentage of Total corrects and Total errors in the primary education group (Bayes factor>100) with males performed better, while such differences eliminated in secondary and tertiary education level. Moreover, 11 differentially expressed proteins (DEPs) between men and women (FDR<0.1) were presented in both education groups, with majority of them upregulated in females. Half of those DEPs interacted directly with nAChR3, whereas the other DEPs were indirectly connected to the cholinergic pathways through interaction with estrogen. These findings implied that Cholinergic-estrogen interaction underpins the effect of education on attenuating cognitive sex differences in a Thai healthy population.
Pilot MRI study of carbon monoxide (CO) against ischemic stroke in mice: blood brain barrier integrity and metabolic pattern
Authors: Oliveira Sara R. , Castelhano João , Sereno José , Petrella Lorena , Castelo-Branco Miguel , Vieira Helena L. A. , Duarte Carlos B.
Published: November 2022

Although stroke is the main cause of brain damage worldwide, stroke therapies are based on blood reperfusion and do not target cerebral parenchyma. Ischemic stroke (representing 87% of all strokes) causes cerebral damage due to oxygen and tissue energy depletion, which lead to acidosis, inflammation, excitotoxicity and oxidative stress. Carbon monoxide (CO) is an endogenous gasotransmitter produced by heme oxygenase cleavage of the heme group. CO promotes cytoprotection by limiting inflammation and preventing cell death in several tissues including the brain. Previous studies have demonstrated the protective role of CO in the mouse ischemic stroke model, middle cerebral artery occlusion (MCAo) by histological analysis when CO is when applied before ischemia. Herein, there are two main novelties. First CO is administrated following stroke, which better mimics its potential future use as therapeutic drug. Secondly, imaging techniques were used to elucidate the effect of this gasotransmitter at the metabolic, vascular and anatomic levels.

The putative neuroprotective effects of CO following MCAo were assessed by 3 i.p. injections of the CO-releasing molecule CORM-A1 (3 mg/kg), administered 6, 24 and 48h after reperfusion. Magnetic Resonance Imaging was performed 1 day and 7 days after reperfusion using T2-weighted, diffusion weighted images, proton spectroscopy (1H-MRS) and perfusion (dynamic contrast enhanced images).1H-MRS also allowed the comparison between metabolite signatures at day 1 versus 7 day following MCAo. Furthermore, CORM-A1 limited the loss of blood-brain barrier (BBB) integrity as it reduced the edema formation. Furthermore, the CO donor minimized the metabolite load loss at an early stage after MCAo, both in striatum and cortex.

In conclusion and based on MRI analysis, CO has a protective role in the recovery from stroke injury, mainly by acting on BBB integrity and brain metabolism.
Central extended amygdala neurons in the development of activity-based anorexia
Authors: Schnapp Wesley Ilana , Kim JungMin , Wang Yong , Timilsena Sayujya , Fang Caohui , Cai Haijiang
Published: November 2022

Anorexia nervosa (AN) is a serious psychiatric disease characterized by restricted eating, fear of gaining weight, as well as excessive exercise, and also is often comorbid with emotional disorders such as anxiety and depression. However, the etiology of AN is unknown and the neural mechanism that leads to AN remains to be determined. Here, we show that a specific subpopulation of neurons, marked by the expression of protein kinase C-delta (PKC-δ), in two nuclei of the central extended amygdala (EAc)— central nucleus (CeA) and oval region of bed nucleus of stria terminalis (ovBNST)—regulates development of activity-based anorexia (ABA), the current best animal model of AN. Specifically, simultaneous dual ablation of CeAPKC-δand ovBNSTPKC-δneurons prevents the key phenotypes of ABA: increases in wheel activity, decreases in food intake, and life-threatening body weight loss. However, ablating PKC-δ neurons in CeA or ovBNST alone is not sufficient to prevent ABA. Correspondingly, activation of PKC-δ neurons in one type of nuclei continues to suppress food intake even when PKC-δ neurons in the other nuclei are silenced. Consistent with their role in suppressing food intake when activated, these PKC-δ neurons show increased activity with ABA development. Together, our study illuminates how neurons in the amygdala regulate ABA development and supports the complex and heterogenous etiology of AN.
Evolution shapes metabolic function and niche-specific antimicrobial targets in pathobionts
Authors: Glass Emma M. , Dillard Lillian R. , Kolling Glynis L. , Warren Andrew S. , Papin Jason A.
Published: November 2022

Treatment of infections with traditional antimicrobials has become difficult due to the growing antimicrobial resistance crisis, necessitating the development of innovative approaches for deeply understanding pathogen function. Here, we generated a collection of genome-scale metabolic network reconstructions to gain insight into evolutionary drivers of metabolic function. We determined physiological location is a major driver of evolution of metabolic function. We observed that stomach-associated pathobionts had the most unique metabolic phenotypes and identified three essential genes unique to stomach pathobionts across diverse phylogenetic relationships. We demonstrate that inhibition of one such gene,thyX, inhibited growth of stomach- specific pathobionts exclusively, indicating possible physiological niche-specific targeting. This pioneering approach is the first step to using unique metabolic signatures to inform targeted antimicrobial therapies.

One sentence summary

A data-driven approach to drug target discovery through metabolic signatures of diverse pathogens conserved across body-sites.
Direct Cortical Inputs to Hippocampal Area CA1 Transmit Complementary Signals for Goal-directed Navigation
Authors: Bowler John C , Losonczy Attila
Published: November 2022

The entorhinal cortex (EC) is central to the brain’s navigation system. Its subregions are conventionally thought to compute dichotomous representations for spatial processing: medial entorhinal cortex (MEC) provides a global spatial map, while lateral entorhinal cortex (LEC) encodes specific sensory details of experience. While local recordings of EC circuits have amassed a vast catalogue of specialized cell types that could support navigation computations in the brain, we have little direct evidence for how these signals are actually transmitted outside of the EC to its primary downstream reader, the hippocampus, which itself is critical for the formation of spatial and episodic memories. Here we exploitin vivosub-cellular imaging to directly record from EC axon terminals as they locally innervate hippocampal area CA1, while mice performed navigational and spatial learning tasks in virtual reality. We find both distinct and overlapping representations of task, location, and context in both MEC and LEC axons. While MEC transmitted a highly location- and context-specific code, LEC inputs were strongly biased by ongoing navigational goals and reward. Surprisingly, the position of the animal could be accurately decoded from either entorhinal subregion. Our results challenge prevailing dogma on the routing of spatial and non-spatial information from the cortex to the hippocampus, indicating that cortical interactions upstream of the hippocampus are critical for combining these processing streams to support navigation and memory.
More hot air: measuring the paradox of European ecology conferences
Authors: Smith Graham C , Begeman Lineke , Coles Alexia , Gilot-Fromont Emmanuelle , López-Olvera Jorge R , Vale Ana , Vogler Barbara R , Kuiken Thijs
Published: November 2022

As scientists we cause an above average carbon footprint for work-related travel. International conferences are a common way for us to meet and discuss, and we do not address the environmental costs of these meetings. Knowing the costs might help us to reduce them. Here we estimated the carbon footprint of the last five physical conferences of the European Wildlife Disease Association (EWDA). We obtained the number of participants from each country for those conferences, and along with assumed travel options, commuting, accommodation, meals and printing, estimated the carbon emissions for each conference. The estimate ranged from 155 to 1205 tons CO2per conference, or 0.7 to 2.4 tons per person. The outlying upper value was due to one joint global conference of the EWDA and the American mother association (WDA), which takes place every eight years. The geocentre was calculated for both the country of origin of the average conference attendants and for the society membership. The former was located in Luxembourg, and the latter near Dusseldorf, Germany, just approximately 170 km to the north. This represents the shortest total distance attendees would travel. Air transport to the conference country was the major source of CO2emissions (87-97%), and the average distance flown per person increased from 1000 km (2010) to over 2000 km (2018), since later conferences were generally further from the geocentre. The biggest reduction in carbon emissions (up to 100 tons CO2) could therefore be achieved by decreasing air travel. This could be brought about by reducing the overall travel distance to the conference, i.e. a conference location near the membership geocentre, or – by a lesser amount – by encouraging travel to the conference by train or bus, i.e. conference location near good public travel hubs, and by promoting virtual attendance. Minor but yet substantial savings could be made elsewhere (2-6 tons CO2), including providing accommodation in greener hotels located closer to the conference venue and offering vegan/local food as the default option.
Fast reoptimization of human motor patterns in non-Earth gravity fields locally induced by a robotic exoskeleton
Authors: Verdel Dorian , Bastide Simon , Geffard Franck , Bruneau Olivier , Vignais Nicolas , Berret Bastien
Published: November 2022

Gravity is a ubiquitous component of our environment that we learnt to optimally integrate in movement control. Yet, altered gravity conditions arise in numerous applications from space exploration to rehabilitation, thereby pressing the sensorimotor system to adapt. Here, we used a robotic exoskeleton to test whether humans can quickly reoptimize their motor patterns in arbitrary gravity fields, ranging from 1g to −1g and passing through Mars- and Moon-like gravities. By comparing the motor patterns of actual arm movements with those predicted by an optimal control model, we show that our participants (N = 61) quickly and optimally adapted their motor patterns to each local gravity condition. These findings show that arbitrary gravity-like fields can be efficiently apprehended by humans, thus opening new perspectives in arm weight support training in manipulation tasks, whether it be for patients or astronauts.
Neuroelectrophysiology-Compatible Electrolytic Lesioning
Authors: Bray Iliana E. , Clarke Stephen E. , Casey Kerriann , Nuyujukian Paul ,   the Brain Interfacing Laboratory
Published: November 2022

Lesion studies have historically been instrumental for establishing causal connections between brain and behavior. They stand to provide additional insight if integrated with multielectrode techniques common in systems neuroscience. Here we present and test a platform for creating electrolytic lesions through chronically implanted, intracortical multielectrode probes without compromising the ability to acquire neuroelectrophysiology. A custom-built current source provides stable current and allows for controlled, repeatable lesions in awake-behaving animals. Performance of this novel lesioning technique was validated using histology fromex vivoandin vivotesting, current and voltage traces from the device, and measurements of spiking activity before and after lesioning. This electrolytic lesioning method avoids disruptive procedures, provides millimeter precision over the extent and submillimeter precision over the location of the injury, and permits electrophysiological recording of single-unit activity from the remaining neuronal population after lesioning. This technique can be used in many areas of cortex, in several species, and theoretically with any multielectrode probe. The low-cost, external lesioning device can also easily be adopted into an existing electrophysiology recording setup. This technique is expected to enable future causal investigations of the recorded neuronal population’s role in neuronal circuit function, while simultaneously providing new insight into local reorganization after neuron loss.
Default But Not Rest: Topological Discrimination Defines the Default Mode Network
Authors: Wang Bo , Zhou Tiangang , He Sheng , Chen Lin
Published: November 2022

The default mode network (DMN), a set of transmodal cortical regions, has historically been argued to serve the internal functions of brain. The discovery of this network highlighted the brain’s intrinsic operations. The DMN generally decreases its activity during tasks and increases its activity during relaxed non-task states. It is important to investigate the nature of the DMN in order to understand the human brain in health and disease. In the current study, we discovered a task-related cortical network we called the Topological Discrimination Network (TDN), which was consistently revealed by contrasting activations from topological discrimination tasks with local geometric discrimination tasks. The TDN and the DMN consist of essentially the same group of brain regions and the fMRI response of topological discrimination in those regions exhibited consistent temporal dynamics with resting state. The robustness of the TDN is supported by multiple experiments performed at different field strengths (3T and 7T MRI scanner) as well as different types of signals measured (BOLD and CBF). The collective results suggest that the process of topological discrimination could almost be considered as a functional “default mode” of our brain. The TDN, like the DMN, could define the functional baseline of brain, with the advantage of functional consistency across participants and experimental sessions.
COVID Seq as Laboratory Developed Test (LDT) for diagnosis of SARS-CoV-2 Variants of Concern (VOC)
Authors: Carpenter Rob E. , Tamrakar Vaibhav K. , Almas Sadia , Brown Emily , Sharma Rahul
Published: November 2022

Rapid classification and detection of SARS-CoV-2 variants have been critical in comprehending the virus’s transmission dynamics. Clinical manifestation of the infection is influenced by comorbidities such as age, immune status, diabetes, and the infecting variant. Thus, clinical management may differ for new variants. For example, some monoclonal antibody treatments are variant-specific. Yet, an FDA-approved test for detecting the SARS-CoV-2 variant is unavailable. A laboratory-developed test (LDT) remains a viable option for reporting the infecting variant for clinical intervention or epidemiological purposes. Accordingly, we have validated the Illumina COVID-Seq assay as an LDT according to the guidelines prescribed by the College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). The limit of detection (LOD) of this test is Ct<30 (∼15 viral copies) and >200X genomic coverage, and the test is 100% specific in the detection of existing variants. The test demonstrated 100% precision in inter-day, intra-day, and intra-laboratory reproducibility studies. It is also 100% accurate, defined by reference strain testing and split sample testing with other CLIA laboratories. Advanta Genetics LDT COVID Seq has been reviewed by CAP inspectors and is under review by FDA for Emergency Use Authorization.
Preliminary Study on the Diagnostic Value of Ultrasonic Shear Wave Dispersion for High-risk Esophageal Gastric Varices in Cirrhosis
Authors: Wang Jiayin , Zhou Hongyu , Li Tinghong , Liu Chuan , Zhao Lei , Xu Baiguo , Yin Weili , Wang Fang , Liang Jing , Jing Xiang , Xiang Huiling
Published: November 2022

Objective

To explore the clinical value of two-dimensional ultrasonic shear wave elastography (SWE) and shear wave dispersion (SWD) in the diagnosis of high-risk esophageal gastric varices with cirrhosis.

Methods

A total of 123 people were included, which were divided into the high-risk esophageal gastric varices (high-risk EGV) group (n =60) and low-risk esophageal gastric varices (low-risk EGV) group (n =63). Both shear wave elastography (SWE) and SWD were adopted to examine each patient’s liver synchronously with the Doppler ultrasonic instrument.

Results

In total patients, the results of SWD and SWE of the high-risk EGV group were significantly higher than low-risk EGV group respectively. According to SWD examination, the area under the curve (AUC) of high-risk EGV was 0.709(95%CI:0.616-0.802), the optimal cutoff value was 14.35 m/s/kHz, the sensitivity and specificity was 81.7% and 57.1%, the AUC of high-risk EGV in patients with compensated cirrhosis was 0.786(95%CI:0.656-0.916), the optimal cutoff value was 14.35 m/s/kHz, the sensitivity and specificity was 86.4% and 61.1%, while the AUC of high-risk EGV in patients with decompensated cirrhosis was 0.637(95%CI: 0.494-0.780). According to SWE, the AUC of high-risk EGV in all patients, patients with compensated cirrhosis, and patients with decompensated cirrhosis was 0.606(95%CI: 0.506-0.706), 0.596(95%CI: 0.449-0.743), and 0.579(95%CI: 0.434-0.725), respectively, indicating limited diagnostic value.

Conclusion

SWD predicted the existence of high-risk EGV in patients with compensated cirrhosis non-invasively and provided a supplementary method to determine whether high-risk EGV exists or not in patients, while SWE had limited diagnostic value.
The Eating Disorders Genetics Initiative (EDGI) United Kingdom
Authors: Monssen Dina , Davies Helena L , Bristow Shannon , Kakar Saakshi , Curzons Susannah C B , Davies Molly R , Ahmad Zain , Bradley John R , Bright Steven , Coleman Jonathan R I , Glen Kiran , Hotopf Matthew , Kelly Emily J , Kuile Abigail R Ter , Malouf Chelsea Mika , Kalsi Gursharan , Kingston Nathalie , McAtarsney-Kovacs Monika , Mundy Jessica , Peel Alicia J , Palmos Alish B , Rogers Henry C , Skelton Megan , Adey Brett N , Lee Sang Hyuck , Virgo Hope , Quinn Tom , Price Tom , Zvrskovec Johan , Eley Thalia C , Treasure Janet , Hübel Christopher , Breen Gerome
Published: November 2022

Objective

The Eating Disorders Genetics Initiative United Kingdom (EDGI UK), part of the National Institute for Health and Care Research (NIHR) Mental Health BioResource, aims to deepen our understanding of the environmental and genetic aetiology of eating disorders. EDGI UK launched in February 2020 and is partnered with the UK eating disorders charity, Beat. There are multiple EDGI branches worldwide.

Method

EDGI UK recruits via media and clinical services. Anyone living in England, at least 16 years old, with a lifetime probable or clinical eating disorder is eligible to sign up online:edgiuk.org. Participants complete online questionnaires, donate a saliva sample for genetic analysis, and consent to medical record linkage and recontact for future studies.

Results

As of September 2022, EDGI UK has recruited 8,397 survey participants: 98% female, 93% white, 97.7% cisgender, 67% heterosexual, and 52% have a university degree. Half (51.7%) of participants have returned their saliva kit. The most common diagnoses are anorexia nervosa (42.7%), atypical anorexia nervosa (31.4%), bulimia nervosa (33.2%), binge-eating disorder (14.6%), and purging disorder (33.5%).

Conclusion

EDGI UK is the largest UK eating disorders study but needs to increase its diversity, and efforts are underway to do so. It also offers a unique opportunity to accelerate eating disorder research, and collaboration between researchers and participants with lived experience, with unparalleled sample size.
Comparing Models of Information Transfer in the Structural Brain Network and Their Relationship to Functional Connectivity: Diffusion Versus Shortest Path Routing
Authors: Neudorf Josh , Kress Shaylyn , Borowsky Ron
Published: November 2022

The relationship between structural and functional connectivity in the human brain is a core question in network neuroscience, and a topic of paramount importance to our ability to meaningfully describe and predict functional outcomes. Graph theory has been used to produce measures based on the structural connectivity network that are related to functional connectivity. These measures are commonly based on either the shortest path routing model or the diffusion model, which carry distinct assumptions about how information is transferred through the network. Unlike shortest path routing, which assumes the most efficient path is always known, the diffusion model makes no such assumption, and lets information diffuse in parallel based on the number of connections to other regions. Past research has also developed hybrid measures that use concepts from both models, which have better predicted the functional connectivity from structural connectivity than shortest path length alone. We examined the extent to which each of these models can account for the structure-function relationship of interest using graph theory measures that are exclusively based on each model. This analysis was performed on multiple parcellations of the Human Connectome Project using multiple approaches, which all converged on the same finding. We found that the diffusion model accounts for much more variance in functional connectivity than the shortest path routing model, suggesting that the diffusion model is better suited to describing the structure-function relationship in the human brain at the macroscale.
Immediate reuse of patch-clamp pipettes with sonification
Authors: Jehasse Kevin , Wetz Sophie , Neumann-Raizel Peter , Kampa Björn M.
Published: November 2022

The patch-clamp technique has revolutionized neurophysiology by allowing to study single neuronal excitability, synaptic connectivity, morphology, and the transcriptomic profile. However, the throughput in recordings is limited because of the manual replacement of patch-pipettes after each attempt which are often also unsuccessful. This has been overcome by automated cleaning the tips in detergent solutions, allowing to reuse the pipette for further recordings. Here, we developed a novel method of automated cleaning by sonicating the tips within the bath solution wherein the cells are placed, reducing the risk of contaminating the bath solution or internal solution of the recording pipette by any detergent and avoiding the necessity of a separate chamber for cleaning. We showed that the patch-pipettes can be used consecutively at least 10 times and that the cleaning process does not negatively impact neither the brain slices nor other patched neurons. This method, combined with automated patch-clamp, highly improves the throughput for single and especially multiple recordings.
CelltypeR: A flow cytometry pipeline to annotate, characterize and isolate single cells from brain organoids
Authors: Thomas Rhalena A. , Sirois Julien , Li Shuming , Gestin Alexandre , Deyab Ghislaine , Piscopo Valerio E. , Lépine Paula , Mathur Meghna , Chen Carol X.Q. , Soubannier Vincent , Goldsmith Taylor M. , Fawaz Lama , Durcan Thomas M. , Fon Edward A.
Published: November 2022

Motivated by the growing number of single cell RNA sequencing datasets (scRNAseq) revealing the cellular heterogeneity in complex tissues, particularly in brain and induced pluripotent stem cell (iPSC)-derived brain models, we developed a high-throughput, standardized approach for reproducibly characterizing cell types in complex neuronal tissues based on protein expression levels. Our approach combines a flow cytometry (FC) antibody panel targeting brain cells with a computational pipeline called CelltypeR, with functions for aligning and transforming datasets, optimizing unsupervised clustering, annotating and quantifying cell types, and statistical comparisons. We applied this workflow to human iPSC-derived midbrain organoids and identified the expected brain cell types, including neurons, astrocytes, radial glia, and oligodendrocytes. Defining gates based on the expression levels of our protein markers, we performed Fluorescence-Activated Cell Sorting of astrocytes, radial glia, and neurons, cell types were then confirmed by scRNAseq. Among the sorted neurons, we identified three subgroups of dopamine (DA) neurons; one reminiscent of substantia nigra DA neurons, the cell type most vulnerable in Parkinson’s disease. Finally, we use our workflow to track cell types across a time course of organoid differentiation. Overall, our adaptable analysis framework provides a generalizable method for reproducibly identifying cell types across FC datasets.
Synaptic and circuit mechanisms prevent detrimentally precise correlation in developing visual system
Authors: Tikidji-Hamburyan Ruben A. , Govindaiah Gubbi , Guido William , Colonnese Matthew T.
Published: November 2022

During development, retinal axons create broad and imprecise connections in the thalamus. This topology, very different from adults, supplies developing thalamic neurons with locally homogeneous synaptic currents and should cause spike correlation between thalamocortical neurons on a millisecond timescale. Such correlations have not been observedin vivo, at these ages, and would likely be maladaptive. Here, we use a biophysical model of the visual thalamus with the membrane and synaptic properties of 7-10 day-old mice to show that the developmentally appropriate dominance of NMDA-receptor currents and absence of strong recurrent inhibitory and excitatory connections prevents precise correlation and preserves topographic information in thalamic spikes. We illustrate possible reasons for this desynchronization using a phenomenological cortical model, which shows impaired network diversity when driven with precisely correlated inputs. Our results suggest that developing synapses and circuits evolved mechanisms to compensate for detrimental, “parasitic” correlation arising from the unrefined and immature circuit.
Behavioral dissection of hunger states inDrosophila
Authors: Weaver KJ , Raju S , Rucker RA , Chakraborty TS , Holt RA , Pletcher SD
Published: November 2022

Hunger is a motivational drive that promotes feeding, and it can be generated by the physiological need to consume nutrients as well as the hedonic properties of food. Brain circuits and mechanisms that regulate feeding have been described, but which of these contribute to the generation of motive forces that drive feeding is unclear. Here, we describe our first efforts at behaviorally and neuronally distinguishing hedonic from homeostatic hunger states inDrosophila melanogasterand propose that this system can be used as a model to dissect the molecular mechanisms that underlie feeding motivation. We visually identify and quantify behaviors exhibited by hungry flies and find that increased feeding duration is a behavioral signature of hedonic feeding motivation. Using a genetically-encoded marker of neuronal activity, we find that the mushroom body (MB) lobes are activated by hedonic food environments, and we use optogenetic inhibition to implicate a dopaminergic neuron cluster (PAM) to α’/β’ MB circuit in hedonic feeding motivation. The identification of discrete hunger states in flies and the development of behavioral assays to measure them offers a framework to begin dissecting the molecular and circuit mechanisms that generate motivational states in the brain.