bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rate versus synchrony codes for cerebellar control of motor behavior
Authors: Herzfeld David J. , Joshua Mati , Lisberger Stephen G. 
Published: February 2023

AbstractControl of movement requires the coordination of multiple brain areas, each containing populations of neurons that receive inputs, process these inputs via recurrent dynamics, and then relay the processed information to downstream populations. Information transmission between neural populations could occur through either coordinated changes in firing rates or the precise transmission of spike timing. We investigate the nature of the code for transmission of signals to downstream areas from a part of the cerebellar cortex that is crucial for the accurate execution of a quantifiable motor behavior. Simultaneous recordings from Purkinje cell pairs in the cerebellar flocculus of rhesus macaques revealed how these cells coordinate their activity to drive smooth pursuit eye movements. Purkinje cells show millisecond-scale coordination of spikes (synchrony), but the level of synchrony is small and likely insufficient to impact the firing of downstream neurons in the vestibular nucleus. Further, analysis of previous metrics for assaying Purkinje cell synchrony demonstrates that these metrics conflate changes in firing rate and neuron-neuron covariance. We conclude that the output of the cerebellar cortex uses primarily a rate code rather than synchrony code to drive activity of downstream neurons and thus control motor behavior.Impact statementInformation transmission in the brain can occur via changes in firing rate or via the precise timing of spikes. Simultaneous recordings from pairs of Purkinje cells in the floccular complex reveals that information transmission out of the cerebellar cortex relies almost exclusively on changes in firing rates rather than millisecond-scale coordination of spike timing across the Purkinje cell population.
Segmental infralesional lower motor neuron abnormalities in patients with sub-acute traumatic spinal cord injury
Authors: Berger Michael J. , Adewuyi Adenike A. , Doherty Christopher , Hanlan Amy K. , Morin Cynthia , O’Connor Russ , Sharma Radhika , Sproule Shannon , Swong Kevin N. , Wu Harvey , Franz Colin K. , Brown Erin 
Published: February 2023

AbstractThe health of the infralesional lower motor neuron (LMN) has received little attention in individuals with traumatic cervical spinal cord injuries (SCI). Infralesional LMN health is clinically relevant in the context of nerve transfer surgery to restore critical upper limb functions, as those demonstrating LMN damage below the neurological level of injury may experience irreversible sequelae of denervation (e.g., atrophy, fibrosis) without timely intervention. In this two-centre retrospective cohort study, we examined the health of the infralesional LMN in individuals with traumatic cervical SCI, using data derived from the clinical electrodiagnostic examination performed early after SCI. We assessed 66 limbs in 42 individuals with traumatic cervical SCI (40 males, mean age = 43.6±17.2, mean duration from injury = 3.3±1.5 months, 25 with motor complete injuries). Analysis was stratified by injury level as 1) C4 and above, 2) C5 and 3) C6-7. EMG performed on representative muscles from C5-6, C6-7, C7-8 and C8-T1, were included in analysis. LMN abnormality was dichotomized as present (abnormal spontaneous activity) or absent. Data were pooled for the most caudal infralesional segment (C8-T1). Overall, a high frequency of denervation potentials was seen in all infralesional segments for all injury levels. The pooled frequency of denervation potentials at C8-T1 was 74.6% of limbs tested. There was also evidence of denervation potentials at the rostral border of the neurological level of injury, as high as 64.3% of C5-6 muscles for C5 injuries. These data support a high prevalence of infralesional LMN abnormality following SCI, which has implications to candidacy, timing of the intervention, donor nerve options and motor prognosis following SCI.
Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice
Authors: Sánchez-León Carlos A , Campos Guillermo Sánchez-Garrido , Fernández Marta , Sánchez-López Alvaro , Medina Javier F , Márquez-Ruiz Javier 
Published: February 2023

AbstractTranscranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuitsin vivo. We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS.Mice (n = 9) were prepared for the chronic recording of LFPs to assess the actual electric field gradient imposed by Cb-tDCS in our experimental design. Single-neuron extracellular recording of PCs in awake (n = 24) and anesthetized (n = 27) mice was combined with juxtacellular recordings and subsequent staining of PC with neurobiotin under anesthesia (n = 8) to correlate their neuronal orientation with their response to Cb-tDCS. Finally, a high-density Neuropixels recording system was used to demonstrate the relevance of neuronal orientation during the application of Cb-tDCS in awake mice (n = 6).In this study, we observe that Cb-tDCS induces a heterogeneous polarity-dependent modulation of the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex. We demonstrate that the apparently heterogeneous effects of tDCS on PC activity can be explained by taking into account the somatodendritic orientation relative to the electric field. Our findings highlight the need to consider neuronal orientation and morphology to improve tDCS computational models, enhance stimulation protocol reliability, and optimize effects in both basic and clinical applications.
Arousal state transitions occlude sensory-evoked neurovascular coupling in neonatal mice
Authors: Gheres Kyle W. , Ünsal Hayreddin S , Han Xu , Zhang Qingguang , Turner Kevin L. , Zhang Nanyin , Drew Patrick J. 
Published: February 2023

AbstractIn the adult sensory cortex, increases in neural activity elicited by sensory stimulation usually drives vasodilation mediated by neurovascular coupling. However, whether neurovascular coupling is the same in neonatal animals as adults is controversial, as both canonical and inverted responses have been observed. We investigated the nature of neurovascular coupling in unanesthetized neonatal mice using optical imaging, electrophysiology, and BOLD fMRI. We find in neonatal (postnatal day 15, P15) mice, sensory stimulation induces a small increase in blood volume/BOLD signal, often followed by a large decrease in blood volume. An examination of arousal state of the mice revealed that neonatal mice were asleep a substantial fraction of the time, and that stimulation caused the animal to awaken. As cortical blood volume is much higher during REM and NREM sleep than the awake state, awakening occludes any sensory-evoked neurovascular coupling. When neonatal mice are stimulated during an awake period, they showed relatively normal (but slowed) neurovascular coupling, showing that that the typically observed constriction is due to arousal state changes. These result show that sleep-related vascular changes dominate over any sensory-evoked changes, and hemodynamic measures need to be considered in the context of arousal state changes.Significance StatementIn the adult brain, increases in neural activity are often followed by vasodilation, allowing activity to be monitored using optical or magnetic resonance imaging. However, in neonates, sensory stimulation can drive vasoconstriction, whose origin was not understood. We used optical and magnetic resonance imaging approaches to investigate hemodynamics in neonatal mice. We found that sensory-induced vasoconstriction occurred when the mice were asleep, as sleep is associated with dilation of the vasculature of the brain relative to the awake state. The stimulus awakens the mice, causing a constriction due to the arousal state change. Our study shows the importance of monitoring arousal state, particularly when investigating subjects that may sleep, and the dominance arousal effects on brain hemodynamics.
The power of family? Family social capital and the risk of externalising behaviours among youth with multiple childhood adversities
Authors: Kysar‐Moon Ashleigh 
Published: February 2023

AbstractExternalising behaviour problems (EBP), or aggressive and delinquent behaviours, among youth pose a significant problem for their peers, parents, teachers and society. Many types of childhood adversities increase the risk of EBP, including maltreatment, physical punishment, domestic violence, family poverty and living in violent neighbourhoods. This study asks, to what extent do children who face multiple adversities during childhood suffer an increased risk of EBP and is family social capital (FSC) associated with a lower risk? Using seven waves of panel data from the Longitudinal Studies of Child Abuse and Neglect, I examine the accumulation of adversities associated with greater risk of EBP among youth and investigate whether FSC—family network, support and cohesion—in early childhood is associated with a reduction in EBP risk. Experiencing early and multiple adversities resulted in the worst EBP trajectories throughout childhood. Although, among youth with the highest adversities, if early family support was also high, their EBP trajectories are more favourable than their disadvantaged peers with less support. FSC may protect against EBP when multiple childhood adversities are experienced. The need for early EBP interventions and bolstering FSC are discussed.
Fetal heart rate responses in chronic hypoxaemia with superimposed repeated hypoxaemia consistent with early labour: a controlled study in fetal sheep
Authors: Lear C. A. , Georgieva A. , Beacom M. J. , Wassink G. , Dhillon S. K. , Lear B. A. , Mills O. J. , Westgate J. A. , Bennet L. , Gunn A. J. 
Published: February 2023

AbstractObjectiveDeceleration area (DA) and capacity (DC) of the fetal heart rate can help predict risk of intrapartum fetal compromise. However, their predictive value in higher risk pregnancies is unclear. We investigated whether they can predict the onset of hypotension during brief hypoxaemia repeated at a rate consistent with early labour in fetal sheep with pre‐existing hypoxaemia.DesignProspective, controlled study.SettingLaboratory.SampleChronically instrumented, unanaesthetised near‐term fetal sheep.MethodsOne‐minute complete umbilical cord occlusions (UCOs) were performed every 5 minutes in fetal sheep with baseline paO2 <17 mmHg (hypoxaemic, n = 8) and >17 mmHg (normoxic, n = 11) for 4 hours or until arterial pressure fell <20 mmHg.Main outcome measuresDA, DC and arterial pressure.ResultsNormoxic fetuses showed effective cardiovascular adaptation without hypotension and mild acidaemia (lowest arterial pressure 40.7 ± 2.8 mmHg, pH 7.35 ± 0.03). Hypoxaemic fetuses developed hypotension (lowest arterial pressure 20.8 ± 1.9 mmHg, P < 0.001) and acidaemia (final pH 7.07 ± 0.05). In hypoxaemic fetuses, decelerations showed faster falls in FHR over the first 40 seconds of UCOs but the final deceleration depth was not different to normoxic fetuses. DC was modestly higher in hypoxaemic fetuses during the penultimate (P = 0.04) and final (P = 0.012) 20 minutes of UCOs. DA was not different between groups.ConclusionChronically hypoxaemic fetuses had early onset of cardiovascular compromise during labour‐like brief repeated UCOs. DA was unable to identify developing hypotension in this setting, while DC only showed modest differences between groups. These findings highlight that DA and DC thresholds need to be adjusted for antenatal risk factors, potentially limiting their clinical utility.
Symptoms of postural orthostatic tachycardia syndrome in pregnancy: a cross‐sectional, community‐based survey
Authors: Bourne Kate M. , Nerenberg Kara A. , Stiles Lauren E. , Shibao Cyndya A. , Okamoto Luis E. , Garland Emily M. , Gamboa Alfredo , Peltier Amanda , Diedrich André , Biaggioni Italo , Sheldon Robert S. , Gibson Paul S. , Kealey Angela J. , Raj Satish R. 
Published: February 2023

AbstractObjectiveTo evaluate the relationship between postural orthostatic tachycardia syndrome (POTS) and pregnancy.DesignCross‐sectional survey.SettingInternational.SampleA total of 8941 female patients with a diagnosis of POTS.MethodsData from the survey were analysed using descriptive measures and stratified for comparisons.Main outcome measuresSymptom course of POTS during pregnancy. Secondary outcomes included pregnancy loss, POTS onset during pregnancy and the impacts of a comorbid diagnosis of Ehlers–Danlos syndrome or an autoimmune disorder on symptoms during pregnancy.ResultsOverall, 40.8% (n = 3652) of participants reported one or more pregnancies. Most participants experienced worsening of symptoms in the first (62.6%) and third (58.9%) trimesters and 3 months after pregnancy (58.7%), and 81.1% experienced worsening symptoms at any point in their pregnancy. Most participants with worsening symptoms in the first trimester also experienced worsening symptoms in the second (61.6%) and third (68.1%) trimesters, but if they improved in the first trimester then this improvement persisted in the second and third trimesters. Of participants who reported that POTS was triggered by a specific event (41.3%), 8.1% reported pregnancy as the trigger for the onset.ConclusionsPostural orthostatic tachycardia syndrome symptoms in the first trimester of pregnancy may help predict symptom course throughout the duration of pregnancy. Some individuals may experience an initial onset of POTS during pregnancy. This novel information may guide clinicians in counselling patients with POTS who are planning pregnancy.
Engineering resource allocation in artificially minimized cells: Is genome reduction the best strategy?
Authors: Marquez‐Zavala Elisa , Utrilla Jose 
Published: February 2023

AbstractThe elimination of the expression of cellular functions that are not needed in a certain well‐defined artificial environment, such as those used in industrial production facilities, has been the goal of many cellular minimization projects. The generation of a minimal cell with reduced burden and less host‐function interactions has been pursued as a tool to improve microbial production strains. In this work, we analysed two cellular complexity reduction strategies: genome and proteome reduction. With the aid of an absolute proteomics data set and a genome‐scale model of metabolism and protein expression (ME‐model), we quantitatively assessed the difference of reducing genome to the correspondence of reducing proteome. We compare the approaches in terms of energy consumption, defined in ATP equivalents. We aim to show what is the best strategy for improving resource allocation in minimized cells. Our results show that genome reduction by length is not proportional to reducing resource use. When we normalize calculated energy savings, we show that strains with the larger calculated proteome reduction show the largest resource use reduction. Furthermore, we propose that reducing highly expressed proteins should be the target as the translation of a gene uses most of the energy. The strategies proposed here should guide cell design when the aim of a project is to reduce the maximum amount or cellular resources.
Microbe–Anode Interactions: Comparing the impact of genetic and material engineering approaches to improve the performance of microbial electrochemical systems (MES)
Authors: Klein Edina M. , Knoll Melanie T. , Gescher Johannes 
Published: February 2023

AbstractMicrobial electrochemical systems (MESs) are a highly versatile platform technology with a particular focus on power or energy production. Often, they are used in combination with substrate conversion (e.g., wastewater treatment) and production of value‐added compounds via electrode‐assisted fermentation. This rapidly evolving field has seen great improvements both technically and biologically, but this interdisciplinarity sometimes hampers overseeing strategies to increase process efficiency. In this review, we first briefly summarize the terminology of the technology and outline the biological background that is essential for understanding and thus improving MES technology. Thereafter, recent research on improvements at the biofilm–electrode interface will be summarized and discussed, distinguishing between biotic and abiotic approaches. The two approaches are then compared, and resulting future directions are discussed. This mini‐review therefore provides basic knowledge of MES technology and the underlying microbiology in general and reviews recent improvements at the bacteria–electrode interface.
Performance of systemic lupus erythematosus responder index for detecting clinician‐rated responders in patients with active systemic lupus erythematosus
Authors: Leosuthamas Pornsawan , Narongroeknawin Pongthorn , Chaiamnuay Sumapa , Asavatanabodee Paijit , Pakchotanon Rattapol 
Published: February 2023

AbstractObjectiveDisease activity measures in systemic lupus erythematosus (SLE) are critical tools for trial endpoints. We aimed to evaluate the performance of current treatment outcome measures in SLE.MethodsIndividuals with active SLE with a clinical SLE Disease Activity Index‐2000 (SLEDAI‐2K) score of at least 4 were followed up for two or more visits and classified as responders and non‐responders based on a physician's judgment of improvement. The treatment outcome measures including SLEDAI‐2K responder index‐50 (SRI‐50), SLE responder index‐4 (SRI‐4), substituting SLEDAI‐2K with SRI‐50 in SRI‐4 (SRI‐4(50)), SLE Disease Activity Score (SLE‐DAS) responder index (Δ ≥ 1.72) and the British Isles Lupus Assessment Group (BILAG)‐based Composite Lupus Assessment (BICLA) were tested. The performance of those measures was shown by sensitivity, specificity, predictive value, positive likelihood ratio, accuracy, and agreement against a physician‐rated improvement.ResultsTwenty‐seven patients with active SLE were followed. The total cumulative pair of visits (baseline and follow up) was 48. The overall accuracies (95% confidence interval [CI]) of SRI‐50, SRI‐4, SRI‐4(50), SLE‐DAS, and BICLA for detecting responders in all patients were 72.9 (58.2‐84.7), 75.0 (60.4‐86.4), 72.9 (58.2‐84.7), 75.0 (60.4‐86.4), and 64.6 (49.5‐77.8), respectively. Subgroup analyses of lupus nephritis (23 patients had a pair of visits) found the accuracies (95% CI) of SRI‐50, SRI‐4, SRI‐4(50), SLE‐DAS, and BICLA were 82.6 (61.2‐95.0), 73.9 (51.6‐89.8), 82.6 (61.2‐95.0), 82.6 (61.2‐95.0), and 78.3 (56.3‐92.5), respectively. However, there were no significant differences between the groups (P > 0.05).ConclusionSRI‐4, SRI‐50, SRI‐4(50), SLE‐DAS responder index, and BICLA demonstrated comparable abilities to identify clinician‐rated responders in patients with active SLE and lupus nephritis.
Focal 18F‐FDG uptake predicts progression of pre‐invasive squamous bronchial lesions to invasive cancers
Authors: Smesseim Illaa , van Boerdonk Robert A. , Dickhoff Chris , Heineman David J. , Dahele Max R. , Radonic Teodora , Bahce Idris , Rauh Simone P. , Comans Emile F. I. , Daniels Hans (J. M. A.) 
Published: February 2023

AbstractIntroductionPre‐invasive squamous lesions of the central airways can progress into invasive lung cancers. Identifying these high‐risk patients could enable detection of invasive lung cancers at an early stage. In this study, we investigated the value of 18F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET) scans in predicting progression in patients with pre‐invasive squamous endobronchial lesions.MethodsIn this retrospective study, patients with pre‐invasive endobronchial lesions, who underwent an 18F‐FDG PET scan at the VU University Medical Center Amsterdam, between January 2000 and December 2016, were included. Autofluorescence bronchoscopy (AFB) was used for tissue sampling and was repeated every 3 months. The minimum and median follow‐up was 3 and 46.5 months. Study endpoints were the occurrence of biopsy proven invasive carcinoma, time‐to‐progression and overall survival (OS).ResultsA total number of 40 of 225 patients met the inclusion criteria of which 17 (42.5%) patients had a positive baseline 18F‐FDG PET scan. A total of 13 of 17 (76.5%) developed invasive lung carcinoma during follow‐up, with a median time to progression of 5.0 months (range, 3.0–25.0). In 23 (57.5%) patients with a negative 18F‐FDG PET scan at baseline, 6 (26%) developed lung cancer, with a median time to progression of 34.0 months (range, 14.0–42.0 months, p < 0.002). With a median OS of 56.0 months (range, 9.0–60.0 months) versus 49.0 months (range, 6.0–60.0 months) (p = 0.876) for the 18F‐FDG PET positive and negative groups, respectively.ConclusionsPatients with pre‐invasive endobronchial squamous lesions and a positive baseline 18F‐FDG PET scan were at high‐risk for developing lung carcinoma, highlighting that this patient group requires early radical treatment.
Type I IFN stimulates lymph node stromal cells from adult and old mice during a West Nile virus infection
Authors: Bennett Allison K. , Richner Michelle , Mun Madeline D. , Richner Justin M. 
Published: February 2023

AbstractAdvanced age is a significant risk factor during viral infection due to an age‐associated decline in the immune response. Older individuals are especially susceptible to severe neuroinvasive disease after West Nile virus (WNV) infection. Previous studies have characterized age‐associated defects in hematopoietic immune cells during WNV infection that culminate in diminished antiviral immunity. Situated amongst immune cells in the draining lymph node (DLN) are structural networks of nonhematopoietic lymph node stromal cells (LNSCs). LNSCs are comprised of numerous, diverse subsets, with critical roles in the coordination of robust immune responses. The contributions of LNSCs to WNV immunity and immune senescence are unclear. Here, we examine LNSC responses to WNV within adult and old DLNs. Acute WNV infection triggered cellular infiltration and LNSC expansion in adults. Comparatively, aged DLNs exhibited diminished leukocyte accumulation, delayed LNSC expansion, and altered fibroblast and endothelial cell subset composition, signified by fewer LECs. We established an ex vivo culture system to probe LNSC function. Adult and old LNSCs both recognized an ongoing viral infection primarily through type I IFN signaling. Gene expression signatures were similar between adult and old LNSCs. Aged LNSCs were found to constitutively upregulate immediate early response genes. Collectively, these data suggest LNSCs uniquely respond to WNV infection. We are the first to report age‐associated differences in LNSCs on the population and gene expression level during WNV infection. These changes may compromise antiviral immunity, leading to increased WNV disease in older individuals.