bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late Component of the Trigemino-Cervical Reflex: Clinical and Neuroradiological Correlations
Authors: Asan Furkan , Gündüz Ayşegül , Kızıltan Meral E. 
Published: October 2021

Introduction:
The authors aimed to analyze the possible relationship of the late response of trigemino-cervical reflex (TCR) with various clinical conditions having brainstem lesions and lesion localizations in the brainstem.

Methods:
The authors enrolled 30 healthy subjects, 16 patients with stroke, 14 patients with multiple sclerosis (MS), and 9 patients with neuro-Behçet disease. All patients had at least one MRI, and lesion localization was classified into midbrain, pons, medulla oblongata, or their combinations. The TCR was recorded simultaneously from bilateral sternocleidomastoid and splenius capitis muscles.

Results:
There was no significant difference based on lesion localization within the brainstem. Trigemino-cervical reflex latency was significantly longer in patients with MS compared with all other groups (P < 0.005 for each comparison). The Receiver Operating Characteristic curve analysis of sternocleidomastoid showed a cut-off value of 76.9 ms with 44% sensitivity and 92.7% specificity to predict MS. Similarly, the authors determined a cut-off value of 61.5 ms of splenius capitis latency with 38.5% sensitivity and 91.5% specificity to predict MS.

Conclusions:
This study showed that TCR might be abnormal in a given patient with one brainstem lesion, independently from the lesion localization. This may be attributed to a broad network of TCR at the brainstem. Thus, abnormally delayed TCR responses can be used as a tool for the discrimination of MS among other brainstem lesions.
Winged Scapula: Clinical and Electrophysiological Features and Common Causes Based on 20 Years of Experience in a Referral Center in Turkey
Authors: Azman Filiz , Yildiz Fatma Gokcem , Temucin Cagri Mesut 
Published: October 2021

Purpose:
Winged scapula (WS) is a functionally disabling problem and it occurs because of neurogenic causes frequently. The authors aimed to assess WS patients by physical and electrodiagnostic examinations as well as some further investigations and define the common causes of WS.

Methods:
The authors reviewed clinical and neurophysiological findings of 52 patients who were referred for electrodiagnostic examination because of WS in the period of 20 years.

Results:
The mean age was 39 (range, 11–73) years and 32 were male patients. Right side was involved in 60% of patients (n = 31). According to electrodiagnostic examinations, 44 patients (85%) had neurogenic causes; 29 spinal accessory nerve palsy (17 occurred after surgical procedure), nine long thoracic nerve palsy (four occurred after strenuous activity), two dorsal scapular nerve (both neuralgic amyotrophy), one long thoracic nerve and spinal accessory nerve (relevant with strenuous trauma), one spinal accessory nerve and dorsal scapular nerve palsies (after surgical procedure and radiotherapy), one C5-7 radiculopathy (avulsion), and one brachial plexopathy (obstetric trauma). Five patients (10%) had muscle-related findings (four facio-scapulo-humeral dystrophy and one Duchenne muscular dystrophia) and three patients (5%) had normal findings (bone-joint related).

Conclusions:
This study presents a relatively large series of patients with WS because of several causes from a referral tertiary EMG laboratory. The authors found that spinal accessory nerve palsy after neck surgery is the most common cause and long thoracic nerve palsy is the second common cause of unilateral WS. Electrodiagnostic examinations should be performed in WS patients to establish exact diagnosis and reveal some coexistence of WS causes.
Mobility network reveals the impact of spatial vaccination heterogeneity on COVID-19
Authors: Yuan Yuan , Jahani Eaman , Zhao Shengjia , Ahn Yong-Yeol , Pentland Alex 
Published: October 2021

ABSTRACTMass vaccination is one of the most effective epidemic control measures. Because one’s vaccination decision is shaped by social processes, the pattern of vaccine uptake tends to show strong social and spatial heterogeneity, such as urban-rural divide and clustering. Examining through network perspectives, we develop a framework for estimating the impact of spatial vaccination heterogeneity on epidemic outbreaks. Leveraging fine-grained mobility data and computational models, we investigate two network effects—the “hub effect” (vaccinating mobility hubs reduces transmission) and the “homophily effect” (stronger homophily in vaccination rates increases transmission). Applying Bayesian deep learning and fine-grained epidemic simulations, our study suggests a negative effect of homophily and a positive effect of highly vaccinated hubs on reducing case counts for both the synthetic network and the U.S. mobility network. Our framework enables us to evaluate outcomes from various hypothetical spatial vaccine distributions and to study a hypothetical vaccination campaign strategy that targets a small number of regions with the largest gain in protective power using the data from January 2022. Our simulation suggests that our strategy can potentially prevent about 2.5 times more cases than a uniform strategy with an additional 1% of the population vaccinated. Notably, our simulation also shows that this strategy could even better protect vulnerable or disadvantaged communities through network effects than strategies that directly target them. Our study suggests that we need to examine the interplay between vaccination patterns and mobility networks beyond the overall vaccination rate, and that understanding geographical pattern of vaccine uptake could be just as important as improving the overall vaccination rate.
Dampening of the respiratory cytokine storm is promoted by inhaled budesonide in patients with early COVID-19
Authors: Baker Jonathan R , Mahdi Mahdi , Nicolau Dan V , Ramakrishnan Sanjay , Barnes Peter J , Simpson Jodie L , Cass Steven P , Russell Richard EK , Donnelly Louise E , Bafadhel Mona 
Published: October 2021

SummaryVaccinations against SARS-CoV-2 are effective in COVID-19. However, with limited vaccine access, vaccine hesitancy and variant breakthroughs, there is still a need for effective and safe early treatments. Two community-based clinical trials of the inhaled corticosteroid, budesonide, have recently been published showing and improvement in patients with COVID-19 treated early with budesonide1,2. To understand mechanistically how budesonide was beneficial, inflammatory mediators were assessed in the nasal mucosa of patients recruited to the Steroids in COVID (STOIC1) trial and a cohort of SARS-CoV-2 negative individuals. Here we show that in early COVID-19, elevation in viral response proteins and Th1 and Th2 inflammation occurs. Longitudinal sampling in the natural course of COVID-19 showed persistently high interferon levels and elevated concentrations of the eosinophil chemokine, CCL11. In patients who deteriorate, the initial nasal mucosal signal is characterised by a marked suppression of the early inflammatory response, with reduced concentrations of interferon and inflammatory cytokines, but elevated eosinophil chemokines. Systemic inflammation remained altered in COVID-19 patients, implying that even after symptom resolution, changes in immunological mediators do not resolve. Budesonide treatment decreased IL-33 and IFN-γ, implying a reduction in epithelial damage and dampening of the interferon response. Budesonide treatment also increased CCL17 concentrations, suggesting an improved T-cell response; and significantly alters inflammatory pathways giving further insight into how this treatment can accelerate patient recovery.Abstract Figure
A miniature kinematic coupling device for mouse head fixation
Authors: Kim Su Jin , Slocum Alexander H. , Scott Benjamin B. 
Published: October 2021

AbstractHead-fixation is a common technique in the preparation of subjects for neuroscience experiments. Accurate alignment, stability, and repeatability during fixation provide experimental consistency, thus enabling the subject to return to the same position over time to provide meaningful data. Head restraint systems inspired by kinematic clamps have been developed to allow micron scale repositioning across imaging epochs in rats. Here we report the development of a light-weight, implantable kinematic coupling (clamp) system that is wearable by mice, and enables repeated positioning to submicron accuracy across imaging epochs. This system uses a stainless steel headplate and a Maxwell-style three-groove kinematic mounting system with magnetic force clamping load. Spheres on the dorsal surface of the headplate provide contact points for vee-groove kinematic features machined into a tabletop mount. Evaluation of the clamp using multiphoton microscopy revealed submicron precision in registration accuracy and stability, allowing cellular resolution calcium imaging in awake, behaving mice. These results indicate that miniaturized implantable kinematic clamps for mice could be valuable for future experiments which require repositioning of subjects across time and different instruments.HighlightsDevelopment of a kinematic clamp for mice for precise repositioning in chronic studies.Headplate and clamp provide stability for cellular resolution imaging during behavior.Ruby contact features enable submicron registration repeatability.
Spatial-temporal analysis of nanoparticles in live tumor spheroids impacted by cell origin and density
Authors: Ahmed-Cox Aria , Pandzic Elvis , Johnston Stuart T. , Heu Celine , McGhee John , Mansfeld Friederike M. , Crampin Edmund J. , Davis Thomas P. , Whan Renee M. , Kavallaris Maria 
Published: October 2021

ABSTRACTNanoparticles hold great preclinical promise in cancer therapy but continue to suffer attrition through clinical trials. Advanced, three dimensional (3D) cellular models such as tumor spheroids can recapitulate elements of the tumor environment and are considered the superior model to evaluate nanoparticle designs. However, there is an important need to better understand nanoparticle penetration kinetics and determine how different cell characteristics may influence this nanoparticle uptake. A key challenge with current approaches for measuring nanoparticle accumulation in spheroids is that they are often static, losing spatial and temporal information which may be necessary for effective nanoparticle evaluation in 3D cell models. To overcome this challenge, we developed an analysis platform, termed the Determination of Nanoparticle Uptake in Tumor Spheroids (DONUTS), which retains spatial and temporal information during quantification, enabling evaluation of nanoparticle uptake in 3D tumor spheroids. Outperforming linear profiling methods, DONUTS was able to measure silica nanoparticle uptake to 10 µm accuracy in both isotropic and irregularly shaped cancer cell spheroids. This was then extended to determine penetration kinetics, first by a forward-in-time, center-in-space model, and then by mathematical modelling, which enabled the direct evaluation of nanoparticle penetration kinetics in different spheroid models. Nanoparticle uptake was shown to inversely relate to particle size and varied depending on the cell type, cell stiffness and density of the spheroid model. The automated analysis method we have developed can be applied to live spheroids in situ, for the advanced evaluation of nanoparticles as delivery agents in cancer therapy.
Electro-mechanical transfection for non-viral primary immune cell engineering
Authors: Sido Jessica M. , Hemphill James B. , McCormack Rameech N. , Beighley Ross D. , Grant Bethany F. , Buie Cullen R. , Garcia Paulo A. 
Published: October 2021

AbstractNon-viral approaches to transfection have emerged a viable option for gene transfer. Electro-mechanical transfection involving use of electric fields coupled with high fluid flow rates is a scalable strategy for cell therapy development and manufacturing. Unlike purely electric field-based or mechanical-based delivery methods, the combined effects result in delivery of genetic material at high efficiencies and low toxicity. This study focuses on delivery of reporter mRNA to show electro-mechanical transfection can be used successfully in human T cells. Rapid optimization of delivery to T cells was observed with efficiency over 90% and viability over 80%. Confirmation of optimized electro-mechanical transfection parameters was assessed in multiple use cases including a 50-fold scale up demonstration. Transcriptome and ontology analysis show that delivery, via electro-mechanical transfection, does not result in gene dysregulation. This study demonstrates that non-viral electro-mechanical transfection is an efficient and scalable method for cell and gene therapy engineering and development.One Sentence SummaryThis study demonstrates that non-viral electro-mechanical transfection is an efficient and scalable method for development of engineered cellular therapies.
Fruit flies subjected to TBI exhibit genotype-dependent changes in seizure incidence and duration
Authors: Krcmarik Tori R , Willes Ashley M , Yang A , Weber Sydney L , Brusich Douglas J 
Published: October 2021

AbstractTraumatic brain injury (TBI) is common and often debilitating. One complication following TBI is post-traumatic seizures (PTS). However, there is a poor understanding of PTS, in part, because it is challenging to model. We sought to develop a fly model of PTS. We used a high-impact trauma (HIT) device to inflict TBI and followed this with behavioral, bang-testing methods to assess seizure behavior. Our results showed PTS incidence was sensitive to genetic background. We also found seizure duration was most pronounced at 30 minutes after injury. Our findings support the efficacy of our fly model for coarse screening of seizure behavior. We expect this model will be useful in first-pass screens intended to identify modifiers of seizure risk following TBI.
Pharmacological impacts on schizophrenia functional analysis: a postmortem proteome study
Authors: Alnafisah Rawan S. , Reigle James , O’Donovan Sinead M , Funk Adam J. , Meller Jaroslaw , Mccullumsmith Robert E. , Shukla Rammohan 
Published: October 2021

ABSTRACTSchizophrenia (SCZ) is a severe and debilitating mental illness. Antipsychotic drugs (APDs) are used to treat both positive and negative SCZ symptoms, by influencing the cellular, subcellular-synaptic, and molecular processes. We posit that these effects influence our understanding of SCZ. To address this, we analyzed postmortem dorsolateral prefrontal cortex grey matter samples from control and SCZ subjects (n=10/group) using liquid-chromatography mass-spectrometry-based proteomics. We retrieved SCZ-altered and APD-influenced proteome-sets using linear and mixed linear models, respectively, and validated them experimentally using independent cohorts and insilico using published datasets. Functional analysis of proteome-sets was contrasted at the biological pathway, cell-type, subcellular-synaptic, and drug-target levels. The SCZ-altered proteome was conserved across several studies from DLPFC and other brain areas and was dependent on drug effect. At the pathway level, we observed an aberrant extracellular event and, except for homeostasis, signal-transduction, cytoskeleton, and dendrites associated downregulated changes, the APDs compensated for the majority of the SCZ-altered pathways. At the cell-type level, the up-and down-regulated SCZ-altered events were associated with two different subsets of striatum projecting layer-5 pyramidal-neurons regulating dopaminergic secretion. At the subcellular synaptic level, compensatory pre- and post-synaptic events were observed. At the drug target level, dopaminergic processes influence the SCZ-altered up-regulated proteome, whereas non-dopaminergic and a diverse array of non-neuromodulatory mechanisms influence the SCZ-altered down-regulated proteome. While these findings are dependent on pharmacological effects, they are also consistent with previous SCZ studies, implying the need to re-evaluate previous results. We discuss our findings in the context of cortico-striatal influence in SCZ-pathology.
FiberNeat: Unsupervised White Matter Tract Filtering
Authors: Chandio Bramsh Qamar , Chattopadhyay Tamoghna , Owens-Walton Conor , Reina Julio E. Villalon , Nabulsi Leila , Thomopoulos Sophia I. , Garyfallidis Eleftherios , Thompson Paul M. 
Published: October 2021

AbstractWhole-brain tractograms generated from diffusion MRI digitally represent the white matter structure of the brain and are composed of millions of streamlines. Such tractograms can have false positive and anatomically implausible streamlines. To obtain anatomically relevant streamlines and tracts, supervised and unsupervised methods can be used for tractogram clustering and tract extraction. Here we propose FiberNeat, an unsupervised white matter tract filtering method. FiberNeat takes an input set of streamlines that could either be unlabeled clusters or labeled tracts. Individual clusters/tracts are projected into a latent space using nonlinear dimensionality reduction techniques, t-SNE and UMAP, to find spurious and outlier streamlines. In addition, outlier streamline clusters are detected using DBSCAN and then removed from the data in streamline space. We performed quantitative comparisons with expertly delineated tracts. We ran FiberNeat on 131 participants’ data from the ADNI3 dataset. We show that applying FiberNeat as a filtering step after bundle segmentation improves the quality of extracted tracts and helps improve tractometry.
Single nuclear transcriptional signatures of dysfunctional brain vascular homeostasis in Alzheimer’s disease
Authors: Tsartsalis Stergios , Fancy Nurun , Smith Amy M. , Khozoie Combiz , Yang Xin , Davey Karen , Willumsen Nanet , McGarry Aisling , Muirhead Robert C. J. , Debette Stephanie , Owen David R. , Matthews Paul M. 
Published: October 2021

AbstractBrain perfusion and normal blood brain barrier integrity are reduced early in Alzheimer’s disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD and control brains to characterise pathological transcriptional signatures. We found that endothelial cells (EC) are enriched for expression of genes associated with susceptibility to AD. EC transcriptional signatures identified mechanisms for impaired β-amyloid clearance. Evidence for immune activation was found with upregulation of interferon signalling genes in EC and in pericytes (PC). Transcriptional signatures suggested dysregulation of vascular homeostasis and angiogenesis with upregulation of pro-angiogenic signals (HIF1A) and metabolism in EC, but downregulation of homeostatic growth factor pathways (VEGF, EGF, insulin) in EC and PC and of extracellular matrix genes in fibroblasts (FB). Our genomic dissection of vascular cell risk gene enrichment suggests a potentially causal role for EC and defines transcriptional signatures associated with microvascular dysfunction in AD.
Oxford Nanopore R10.4 long-read sequencing enables near-perfect bacterial genomes from pure cultures and metagenomes without short-read or reference polishing
Authors: Sereika Mantas , Kirkegaard Rasmus Hansen , Karst Søren Michael , Michaelsen Thomas Yssing , Sørensen Emil Aarre , Wollenberg Rasmus Dam , Albertsen Mads 
Published: October 2021

ABSTRACTLong-read Oxford Nanopore sequencing has democratized microbial genome sequencing and enables the recovery of highly contiguous microbial genomes from isolates or metagenomes. However, to obtain near-perfect genomes it has been necessary to include short-read polishing to correct insertions and deletions derived from homopolymer regions. Here, we show that Oxford Nanopore R10.4 can be used to generate near-perfect microbial genomes from isolates or metagenomes without shortread or reference polishing.
Balancing memory fidelity and representational stability in the female mouse accessory olfactory bulb
Authors: Yoles-Frenkel Michal , Shea Stephen D. , Davison Ian G. , Ben-Shaul Yoram 
Published: October 2021

AbstractSensory systems must balance the value of efficient coding schemes against the need to update specific memorized representations without perturbing other memories. Here we describe a unique solution to this challenge that is implemented by the vomeronasal system (VNS) to encode and remember multiple conspecific individuals as part of the Bruce Effect (BE). In the BE, exposure of a pregnant female mouse to the odors of an unfamiliar male leads to failure of the pregnancy (‘pregnancy block’) via the VNS. Following mating and sensory exposure, however, the female becomes protected from a pregnancy block by the stud individual. While this form of natural learning has been proposed to depend on changes in the representation of his odors in her accessory olfactory bulb (AOB), a key VNS structure, there are no direct comparisons of in vivo sensory responses before and after imprinting. It has further been suggested that these changes simply render the AOB insensitive to stud odors. However, the combinatorial odor code used by the AOB and the significant overlap in the odor composition of different males means that silencing responses to one individual is likely to degrade responses to others, posing potential problems for more general sensory encoding. To identify the neuronal correlates of learning in the context of the BE, we recorded extracellular responses of AOB neurons in vivo in mated and unmated female mice upon controlled presentation of urinary chemosignals, including urine from both the stud and males of a distinct strain. We find that while initial sensory responses in the AOB (within a timescale required to guide social interactions) remain stable, responses to extended stimulation (as required for eliciting the pregnancy block) display selective attenuation of stud-responsive neurons. Based on our results, we propose a model that reconciles the formation of strong, selective memories with the need to sustain robust representational bandwidth by noting a distinction between the representations of brief and extended stimuli. This temporal disassociation allows attenuation of slow-acting endocrine processes in a stimulus-specific manner, without compromising consistent ongoing representations of stimuli that guide behavior.