bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human dorsal root ganglia after plexus injury: either preservation or loss of the multicellular unit
Authors: Schulte Annemarie , Degenbeck Johannes , Aue Annemarie , Schindehütte Magnus , Schlott Felicitas , Schneider Max , Monoranu Camelia Maria , Bohnert Michael , Pham Mirko , Antoniadis Gregor , Blum Robert , Rittner Heike L 
Published: February 2023

AbstractObjectivePlexus injury results in lifelong suffering of flaccid paralysis, sensory loss, and intractable pain. For this clinical problem, regenerative medicine concepts, such as cell replacement for restoring dorsal root ganglion (DRG) function, set high expectations. However, it is completely unclear which DRG cell types are affected by plexus injury.MethodsWe investigated the cellular composition of human DRG in a clinically characterized cohort of patients with plexus injury. Avulsed DRG of 13 patients were collected during reconstructive nerve surgery. Then, we analyzed the cellular composition of the DRG with a human-adapted objective deep learning-based analysis of large-scale microscopy images.ResultsSurprisingly, in about half of the patients, the injury-affected DRG no longer contained DRG cells. The complete entity of neurons, satellite glial cells, and microglia was lost and replaced by mesodermal/connective tissue. In the other half of patients, the cellular entity of the DRG was well preserved. We found no loss of neurons, no gliosis, and macrophages close to single sensory neuron/satellite glial cell entities. Patients with ‘neuronal preservation’ had less pain than patients with ‘neuronal loss’.InterpretationThe findings classify plexus injury patients in two categories: type I (neuronal preservation) and type II (neuronal loss). We call for early, post-accidental interventions to protect the entire DRG and improved MRI diagnostics to detect ‘neuronal loss’. Regenerative medicine to restore DRG function will need at least two translational directions: reafferentation of existing DRG units for type I injuries; or replacement of the entire DRG structure for type II patients.
Odor imagery but not perception drives risk for food cue reactivity and increased adiposity
Authors: Perszyk Emily E. , Davis Xue S. , Djordjevic Jelena , Jones-Gotman Marilyn , Trinh Jessica , Hutelin Zach , Veldhuizen Maria G. , Koban Leonie , Wager Tor D. , Kober Hedy , Small Dana M. 
Published: February 2023

ABSTRACTMental imagery has been proposed to play a critical role in the amplification of cravings. Here we tested whether olfactory imagery drives food cue reactivity strength to promote adiposity in 45 healthy individuals. We measured odor perception, odor imagery ability, and food cue reactivity using self-report, perceptual testing, and neuroimaging. Adiposity was assessed at baseline and one year later. Brain responses to real and imagined odors were analyzed with univariate and multivariate decoding methods to identify pattern-based olfactory codes. We found that the accuracy of decoding imagined, but not real, odor quality correlated with a perceptual measure of odor imagery ability and with greater adiposity changes. This latter relationship was mediated by cue-potentiated craving and intake. Collectively, these findings establish odor imagery ability as a risk factor for weight gain and more specifically as a mechanism by which exposure to food cues promotes craving and overeating.
Altered IL-6 signalling and risk of tuberculosis disease: a meta-analysis and Mendelian randomisation study
Authors: Hamilton Fergus , Schurz Haiko , Yates Tom A. , Gilchrist James J. , Möller Marlo , Naranbhai Vivek , Ghazal Peter , Timpson Nicholas J ,   International Host TB Genetics Consortium, Parks Tom , Pollara Gabriele 
Published: February 2023

SummaryIL-6 responses are ubiquitous inMycobacterium tuberculosis (Mtb)infections, but their role in determining human tuberculosis (TB) disease risk is unknown. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor(IL6R)gene, focusing on the non-synonymous variant, rs2228145, associated with reduced classical IL-6 signalling, to assess the effect of altered IL-6 activity on TB disease risk. We identified 16 genome wide association studies (GWAS) of TB disease collating 17,982 cases of TB disease and 972,389 controls across 4 continents. Meta-analyses and Mendelian randomisation analyses revealed that reduced classical IL-6 signalling was associated with lower odds of TB disease, a finding replicated using multiple, independent SNP instruments and 2 separate exposure variables. Our findings establish a causal relationship between IL-6 signalling and the outcome ofMtbinfection, suggesting IL-6 antagonists do not increase the risk of TB disease and should be investigated as adjuncts in treatment.
Month-to-month all-cause mortality forecasting: A method to rapidly detect changes in seasonal patterns
Authors: Léger Ainhoa-Elena , Silvia Rizzi 
Published: February 2023

AbstractBackgroundShort-term forecasts of all-cause mortality are used retrospectively to estimate the baseline mortality and to obtain excess death after mortality shocks, such as heatwaves and pandemics, have occurred. In this study we propose a flexible method to forecast all-cause mortality in real-time and to rapidly identify short-term changes in all-cause mortality seasonal patterns within an epidemiological year.MethodsWe use all-cause monthly death counts and ratios of death counts between adjacent months as inputs. The ratio between one month (earlier month) and the consecutive month (later month) is called later/earlier ratio. We forecast the deaths one-month-ahead based on their proportion to the previous month, defined by the average later/earlier ratio over the preceding years. We provide forecasting intervals by way of a bootstrapping procedure.ResultsThe method is applied to monthly mortality data for Denmark, France, Spain, and Sweden from 2012 through 2022. Over the epidemiological years before COVID-19, the method captures the variations in winter and summer mortality peaks. The results reflect the synchrony of COVID-19 waves and the corresponding mortality burdens in the four analyzed countries. The forecasts show a higher level of accuracy compared to traditional models for short-term forecasting, i.e., 5-year-average method and Serfling model.ConclusionThe method proposed is attractive for health researchers and governmental offices to aid public health responses, because it uses minimal input data, i.e., monthly all-cause mortality data, which are timely available and comparable across countries.KeymessagesWhat is already known on this topic: There is a lack of methods to forecast all-cause mortality in the short-term in a timely or near real-time manner.What this study adds: The method that we propose forecasts all-cause mortality one month ahead assuming a seasonal mortality structure and adjusting it to the level of mortality of the epidemic year. These aspects make the method suitable for forecasting in a timely manner also during mortality shocks, such as the current COVID-19 pandemic.How this study might affect research, practice or policy: The forecasts obtained with the proposed method detects changes in all-cause mortality patterns in a timely manner and can be used to aid public health responses.
Should bionic limb control mimic the human body? Impact of control strategy on bionic hand skill learning
Authors: Schone Hunter R. , Udeozor Malcolm , Moninghoff Mae , Rispoli Beth , Vandersea James , Lock Blair , Hargrove Levi , Makin Tamar R , Baker Chris I. 
Published: February 2023

ABSTRACTA longstanding engineering ambition has been to design anthropomorphic bionic limbs: devices that look like and are controlled in the same way as the biological body (biomimetic). The untested assumption is that biomimetic motor control enhances device embodiment, learning, generalization, and automaticity. To test this, we compared biomimetic and non-biomimetic control strategies for able-bodied participants when learning to operate a wearable myoelectric bionic hand. We compared motor learning across days and behavioural tasks for two training groups: Biomimetic (mimicking the desired bionic hand gesture with biological hand) and Arbitrary control (mapping an unrelated biological hand gesture with the desired bionic gesture). For both trained groups, training improved bionic limb control, reduced cognitive reliance, and increased embodiment over the bionic hand. Biomimetic users had more intuitive and faster control early in training. Arbitrary users matched biomimetic performance later in training. Further, arbitrary users showed increased generalization to a novel control strategy. Collectively, our findings suggest that biomimetic and arbitrary control strategies provide different benefits. The optimal strategy is likely not strictly biomimetic, but rather a flexible strategy within the biomimetic to arbitrary spectrum, depending on the user, available training opportunities and user requirements.
Corticosterone enhances formation of non-fear but not fear memory during infectious illness
Authors: Hill Alice , Johnston Colin , Agranoff Isaac , Gavade Swapnil , Spencer-Segal Joanna 
Published: February 2023

AbstractSurvivors of critical illness are at high risk of developing post-traumatic stress disorder (PTSD) but administration of glucocorticoids during the illness can lower that risk. The mechanism is not known but may involve glucocorticoid modulation of hippocampal- and amygdalar-dependent memory formation. In this study, we sought to determine whether glucocorticoids given during an acute illness influence the formation and persistence of fear and non-fear memories from the time of the illness. We performed cecal ligation and puncture in male and female mice to induce an acute infectious illness. During the illness, mice were introduced to a neutral object in their home cage and separately underwent contextual fear conditioning. We then tested the persistence of object and fear memories after recovery. Glucocorticoid treatment enhanced object discrimination but did not alter the expression of contextual fear memory. During context re-exposure, neural activity was elevated in the dentate gyrus irrespective of fear conditioning. Our results suggest that glucocorticoids given during illness enhance hippocampal-dependent non-fear memory processes. This indicates that PTSD outcomes in critically ill patients may be improved by enhancing non-fear memories from the time of their illness.
Parkinsonian rest tremor can be distinguished from voluntary hand movements based on subthalamic and cortical activity using machine learning
Authors: Todorov Dmitrii , Schnitzler Alfons , Hirschmann Jan 
Published: February 2023

AbstractTremor is one of the cardinal symptoms of Parkinson’s disease. The neurophysiology of tremor is not completely understood, and so far it has not been possible to distinguish tremor from voluntary hand movements based on local brain signals.Here, we re-analyzed magnetoencephalography and local field potential recordings from the subthalamic nucleus of six patients with Parkinson’s disease. Data were obtained after withdrawal from dopaminergic medication (Med Off) and after administration of levodopa (Med On). Using gradient-boosted tree learning, we classified epochs as tremor, self-paced fist-clenching, static forearm extension or tremor-free rest.While decoding performance was low when using subthalamic activity as the only feature (balanced accuracy mean: 38%, std: 7%), we could distinguish the four different motor states when considering cortical and subthalamic features (balanced accuracy mean: 75%, std: 17%). Adding a single cortical area improved classification by 17% on average, as compared to classification based on subthalamic activity alone. In most patients, the most informative cortical areas were sensorimotor cortical regions. Decoding performance was similar in Med On and Med Off.Our results demonstrate the advantage of monitoring cortical signals in addition to subthalamic activity for movement classification. By combining cortical recordings, subcortical recordings and machine learning, future adaptive systems might be able to detect tremor specifically and distinguish between several motor states.
A Novel Single Vector Intersectional AAV Strategy for Interrogating Cellular Diversity and Brain Function
Authors: Hughes Alex C. , Pollard Brittany G. , Xu Beisi , Gammons Jesse W. , Chapman Phillip , Bikoff Jay B. , Schwarz Lindsay A. 
Published: February 2023

AbstractAs the discovery of cellular diversity in the brain accelerates, so does the need for functional tools that target cells based on multiple features, such as gene expression and projection target. By selectively driving recombinase expression in a feature-specific manner, one can utilize intersectional strategies to conditionally promote payload expression only where multiple features overlap. We developed Conditional Viral Expression by Ribozyme Guided Degradation (ConVERGD), a single-construct intersectional targeting strategy that combines a self-cleaving ribozyme with traditional FLEx switches. ConVERGD offers benefits over existing platforms, such as expanded intersectionality, the ability to accommodate larger and more complex payloads, and a vector design that is easily modified to better facilitate rapid toolkit expansion. To demonstrate its utility for interrogating neural circuitry, we employed ConVERGD to target an unexplored subpopulation of norepinephrine (NE)-producing neurons within the rodent locus coeruleus (LC) identified via single-cell transcriptomic profiling to co-express the stress-related endogenous opioid gene prodynorphin (Pdyn). These studies showcase ConVERGD as a versatile tool for targeting diverse cell types and revealPdyn-expressing NE+LC neurons as a small neuronal subpopulation capable of driving anxiogenic behavioral responses in rodents.
Fast and artifact-free excitation multiplexing using synchronized image scanning
Authors: Bruggeman Ezra , Van den Eynde Robin , Amouroux Baptiste , Venneman Tom , Vanden Berghe Pieter , Müller Marcel , Vandenberg Wim , Dedecker Peter 
Published: February 2023

AbstractWe present the Resonator, a simple optical device that provides quasi-simultaneous fluorescence imaging with multiple excitation wavelengths. The device uses a resonant scanning mirror to periodically displace the sample image on a camera sensor at a rate that is much faster than the image acquisition rate. The excitation light is synchronized with the scanner motion to create two laterally shifted copies of the image, each containing the fluorescence excited by a single wavelength. The additional information is then encoded either into the point-spread function of the imaging or as multiple distinct images. Since this multiplexing is performed at very high rates, our design can eliminate or mitigate artifacts caused by temporal aliasing in conventional sequential imaging. We demonstrate the use of our system for the monitoring of fast light-induced dynamics in single quantum dots and for the imaging of Ca2+signalling in hippocampal neurons.
Counterintuitive effect of antiviral therapy on influenza A-SARS-CoV-2 coinfection due to viral interference
Authors: Cheemarla Nagarjuna R. , Mihaylova Valia T. , Watkins Timothy A. , Foxman Ellen F. 
Published: February 2023

AbstractThe resurgence of influenza and continued circulation of SARS-CoV-2 raise the question of how these viruses interact in a co-exposed host. Here we studied virus-virus and host-virus interactions during influenza A virus (IAV) -SARS-CoV-2 coinfection using differentiated cultures of the human airway epithelium. Coexposure to IAV enhanced the tissue antiviral response during SARS-CoV-2 infection and suppressed SARS-CoV-2 replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the antiviral response and paradoxically restored SARS-CoV-2 replication. These results highlight the importance of diagnosing coinfections and compel further study of how coinfections impact the outcome of antiviral therapy.
Stimulus-induced theta band LFP oscillations format neuronal representations of social chemosignals in the mouse accessory olfactory bulb
Authors: Cohen Oksana , Kahan Anat , Steinberg Idan , Malinowski Sebastian , Rokni Dan , Spehr Marc , Ben-Shaul Yoram 
Published: February 2023

AbstractSocial communication is crucial for survival of many species. In most vertebrates, a dedicated chemosensory system, the vomeronasal system (VNS), evolved to process ethologically relevant chemosensory cues. The first central VNS stage is the accessory olfactory bulb (AOB), which sends information to downstream brain regions via AOB mitral cells (AOB-MCs). Recent studies provided important insights about the functional properties of AOB-MCs, but little is known about the principles that govern their coordinated activity. Here, we recorded local field potentials (LFPs) and single unit activity in the AOB while presenting natural stimuli to adult male and female mice. Our recordings reveal prominent LFP theta band oscillatory episodes with a characteristic spatial pattern across the AOB. We find that the AOB network shows varying degrees of similarity to this pattern throughout an experiment, as a function of sensory stimulation. Analysis of LFP signal polarity and single unit activity indicate that oscillatory episodes are generated locally within the AOB, likely representing a reciprocal interaction between AOB-MCs and granule cells (GCs). Notably, spike times of many AOB-MCs are constrained to the negative LFP oscillation phase, in a manner that can drastically affect integration by downstream processing stages. Based on these observations, we propose that LFP oscillations may gate, bind, and organize outgoing signals from individual AOB neurons to downstream processing stages. Our findings suggest that, as in other neuronal systems and brain regions, population level oscillations play a key role in organizing and enhancing transmission of socially relevant chemosensory information.
Sharp wave ripple coupling in zebrafish hippocampus and basolateral amygdala
Authors: Blanco I. , Caccavano A. , Wu J. , Vicini S. , Glasgow E. , Conant K. 
Published: February 2023

ABSTRACTThe mammalian hippocampus exhibits sharp wave events (1-30 Hz) with an often-present superimposed fast ripple oscillation (120-200 Hz) forming a sharp wave ripple (SWR) complex. During slow wave sleep or consummatory behaviors, SWRs result from the sequential spiking of hippocampal cell assemblies initially activated during imagined or learned experiences. SWRs occur in tandem with cortical/subcortical assemblies critical to the long-term storage of specific memory types. Leveraging juvenile zebrafish, we show that SWR events in their hippocampal homologue, the anterodorsolateral lobe (ADL), inex vivowhole-brains are locally generated and maintained. SWR events were also recorded in the basolateral amygdala (BLA). Concomitant single cell calcium imaging and local field potential (LFP) recordings showed that BLA SWs couple to ADL SWs. Calcium imaging recordings of whole-brains demonstrated that ADL and BLA SWRs are endogenously and spontaneously silenced by the activation of a more caudal population of putative cholinergic cells. Electrical stimulation of this caudal region silenced ADL SWs. Our results suggest that the SWR-generating circuit is evolutionarily conserved through shared acetylcholine modulating mechanisms. These findings further our understanding of neuronal population dynamics in the zebrafish brain and highlights their advantage for simultaneously recording SW/SWRs and single cell activity in diverse brain regions.
HiExM: high-throughput expansion microscopy enables scalable super-resolution imaging
Authors: Day John H. , Della Santina Catherine Marin , Maretich Pema , Auld Alexander L. , Schnieder Kirsten K. , Shin Tay , Boyden Edward S. , Boyer Laurie A. 
Published: February 2023

AbstractExpansion microscopy (ExM) enables nanoscale imaging using a standard confocal microscope through the physical, isotropic expansion of fixed immunolabeled specimens. ExM is widely employed to image proteins, nucleic acids, and lipid membranes in single cells; however, current methods limit the number of samples that can be processed simultaneously. We developed High-throughput Expansion Microscopy (HiExM), a robust platform that enables expansion microscopy of cells cultured in a standard 96-well plate. Our method enables ∼4.2x expansion of cells within individual wells, across multiple wells, and between plates. We also demonstrate that HiExM can be combined with high-throughput confocal imaging platforms to greatly improve the ease and scalability of image acquisition. As an example, we analyzed the effects of doxorubicin, a known cardiotoxic agent, on human cardiomyocytes (CMs) as measured by Hoechst signal across the nucleus. We show a dose dependent effect on nuclear DNA that is not observed in unexpanded CMs, suggesting that HiExM improves the detection of cellular phenotypes in response to drug treatment. Our method broadens the application of ExM as a tool for scalable super-resolution imaging in biological research applications.Significance StatementExpansion microscopy (ExM) is an accessible and widely used technique for super-resolution imaging of fixed biological specimens. For many ExM users, slide-based sample preparation and manual imaging limit the number of experimental conditions and samples that can be processed in parallel. Here, we develop a simple and inexpensive device that enables ExM within the wells of a standard 96-well cell culture plate. We show that samples prepared with our workflow can be imaged with a high-throughput autonomous confocal microscope, allowing for scalable super-resolution image acquisition, greatly increasing data output. Our device retains the accessibility of ExM while extending its application to research questions that require the analysis of many conditions, treatments, and time points.