bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electron microscopic visualization of single molecules by tag-mediated metal particle labeling
Authors: Shigemoto Ryuichi 
Published: November 2021

Abstract
Genetically encoded tags have introduced extensive lines of application from purification of tagged proteins to their visualization at the single molecular, cellular, histological and whole-body levels. Combined with other rapidly developing technologies such as clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, proteomics, super-resolution microscopy and proximity labeling, a large variety of genetically encoded tags have been developed in the last two decades. In this review, I focus on the current status of tag development for electron microscopic (EM) visualization of proteins with metal particle labeling. Compared with conventional immunoelectron microscopy using gold particles, tag-mediated metal particle labeling has several advantages that could potentially improve the sensitivity, spatial and temporal resolution, and applicability to a wide range of proteins of interest (POIs). It may enable researchers to detect single molecules in situ, allowing the quantitative measurement of absolute numbers and exact localization patterns of POI in the ultrastructural context. Thus, genetically encoded tags for EM could revolutionize the field as green fluorescence protein did for light microscopy, although we still have many challenges to overcome before reaching this goal.
ASSESSMENT OF OCCUPATIONAL RADIATION DOSE FROM CAMERA MODEL INTRAORAL HANDHELD X-RAY DEVICE WITHOUT STRAY RADIATION PROTECTION SHIELD
Authors: Moshfeghi Mahkameh , Safi Yaser , Afzalan Alireza , Ghazizadeh Ahsaie Mitra 
Published: November 2021

AbstractThe aim of this study was to assess the occupational exposure from portable X-ray device without stray radiation protection shield measured using thermoluminescent dosemeters (TLDs). A total of 108 intraoral periapical radiographies of six sextants were performed. The TLDs were located on right index finger and left palm, between the pupils of the eyes at the edges of the Nasion point, Manubrium of Sternum bone and genital area. The detected mean doses per procedure were 70, 99, 60, 51, 51 and 58 μSv in the right finger, left palm, level of the Nasion point, under left clavicle, above the sternum manubrium and at the gonad area, respectively. Maximum number of radiographic images that the operator is allowed to perform depends on eye exposure and in accordance with International Commission on Radiological Protection is 0.16 (0.12–0.23) per hour or 1.28 (0.96–1.84) per day.
Management of a Pelvic Abscess and Abdominal Fistula after Palliative Total Pelvic Exenteration with Intraoperative Radiotherapy in Recurrent Rectal Cancer Without NPWT: A Case Report
Authors: Yang Hui , Rui Yuanyi , Chen Hong 
Published: November 2021

ABSTRACT
A 59-year-old man with recurrent rectal cancer and type 2 diabetes mellitus underwent palliative total pelvic exenteration and intraoperative radiotherapy. After surgery, he experienced a pelvic abscess and abdominal-perineal fistula. Profuse exudate contaminated the midline abdominal incision through the abdominal-perineal fistula and delayed healing. Because of a residual tumor and the high cost, negative-pressure wound therapy was not performed. After 76 days of local treatment that involved removing necrotic tissue, controlling inflammation with an antimicrobial silver dressing, absorbing and draining exudate with a hypertonic saline dressing, promoting granulation and preventing infection with a silver alginate dressing, and promoting re-epithelialization with recombinant human epidermal growth factor gel, the abdominal wound and abdominal-perineal fistula healed successfully.
Graded Chronic Pain Scale
Authors: Sharma Sonia , Kallen Michael A. , Ohrbach Richard 
Published: November 2021

Objectives:
The 1-month Graded Chronic Pain Scale (GCPS) commonly used in clinical studies has never been validated. This study compares the GCPS 1-month with the 6 months version for reliability and validity.

Methods:
The Validation Project included 521 participants with at least one temporomandibular disorder for cross-sectional data and 74 participants for test-retest data. Internal reliability, stability, and construct validity were used for testing the 1-month version. Comparisons were made between the 2 versions for characteristic pain intensity (CPI), interference, and chronic pain grade (CPG).

Results:
For GCPS 1-month, internal consistency for pain intensity and interference was high (Cronbach α=0.87 and 0.94, respectively), and temporal stability was high for CPI (intraclass correlation coefficient [ICC]=0.91), interference (ICC=0.85), and CPG (weighted κ=0.88). ICC or κ between the 2 versions was 0.78 (CPI), 0.66 (interference), and 0.69 (CPG); high-impact pain, in contrast, was 0.50. Construct validity exhibited higher correlations with predictor variables for 1-month version attributes of CPI, interference, and CPG. Modified Bland-Altman plots indicated that both versions measure CPI well.

Discussion:
Overall, reliability of the 1-month GCPS is equal to or better than the 6-months version for pain intensity, disability days, pain interference, CPG, and high-impact pain. However, consistency between versions is lower for measures of disability days and interference, and for the derived measures of CPG and high-impact pain; highly skewed distributions and increasing disagreement in reported status over the time periods affect the measures of function. Therefore, we recommend that GCPS-1 month only be used to calculate pain intensity and pain interference.
Food Insecurity Negatively Impacts Gluten Avoidance and Nutritional Intake in Patients With Celiac Disease
Authors: Ma Christopher , Singh Siddharth , Jairath Vipul , Radulescu Gabriela , Ho Stephanie K.M. , Choi May Y. 
Published: November 2021

Background:
Food insecurity is a major public health challenge. For patients with celiac disease (CeD), food insecurity may be particularly detrimental as it threatens the cornerstone of their treatment: adoption of a gluten-free diet (GFD). We aimed to characterize the prevalence of food insecurity in patients with CeD and evaluate its impact on GFD adoption and nutritional intake.

Methods:
We analyzed data from patients with CeD participating in the US National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014. Food insecurity was defined using the US Department of Agriculture 18-Item Standard Food Security Survey Module. Survey-weighted logistic regression was used to assess differences in demographic characteristics of CeD patients living with food insecurity and the impact of food security on GFD adoption. Multivariable survey-weighted linear regression was used to evaluate the effect of food insecurity on nutritional intake of macronutrients and micronutrients.

Results:
Overall, 15.9% (95% confidence interval: 10.6%, 23.1%) of patients with CeD in the United States [weighted N=2.9 million (95% confidence interval: 2.2, 3.5 million)] are food insecure. Food insecure patients with CeD were disproportionately younger, poorly educated, nonwhite, living in poverty, and were significantly less likely to adopt a GFD (24.1% vs. 67.9%, P=0.02). Food insecurity was associated with significantly lower consumption of protein, carbohydrates, fat, and most vitamins and minerals.

Conclusions:
One in 6 patients with CeD are food insecure, negatively impacting GFD adoption and the ability to meet recommended daily intake of most micronutrients. Less than one quarter of food insecure CeD patients adhere to a GFD.
Longitudinal Trends in Pediatric Return Visits to US Emergency Departments
Authors: Holmstrom Sara E. , Varma Selina , Augustine Erin , Wilson Paria M. , Ramgopal Sriram 
Published: November 2021

Objectives
This study aimed to evaluate trends in pediatric emergency department (ED) 72-hour return visits and factors associated with return visits.

Methods
We performed a cross-sectional study from 2002 to 2018 using the National Hospital Ambulatory Medical Care Survey, a complex survey of nonfederal US ED encounters. Patients 18 years or older were excluded. Our outcome of interest was 72-hour return ED encounter. We assessed changes in proportions of return visits over time using the Spearman rank-correlation test. We performed survey-weighted univariable and multivariable logistic regressions to identify factors associated with 72-hour return visit status.

Results
A total of 501 million (95% confidence interval [CI], 452–551 million) pediatric survey-weighted ED encounters occurred during the 17-year study period, of which 14,353,697 (3.2%; 95% CI, 2.7%–3.7%) represented 72-hour return visits. The proportion of pediatric ED return visits increased from 22.9 to 36.5 per 1000 pediatric encounters over the study period (ρ = 0.68, P < 0.01). Most return visits were of lower acuity (73.0%; 95% CI, 68.6%–11.5%), and 8.1% (95% CI, 6.3%–9.9%) of return visits were admitted to the hospital or transferred to a different facility. In multivariable analyses, older age, abnormal heart rate, and abnormal temperature had lower adjusted odds ratio (aOR) of 72-hour return visits compared with encounters not classified as return visit. Complaints of returning for test results, treatment, and diagnostic screening/administrative purposes were associated with a higher aOR of return visit. Admission/transfer (in comparison with discharge) had a higher odds of return visit status in univariable (odds ratio, 1.59; 95% CI, 1.24–2.04) and multivariable (aOR, 1.31; 95% CI, 1.03–1.68) analyses.

Conclusions
The proportion of 72-hour US pediatric ED return visits is increasing over time. Return visit status was associated with admission/transfer, but otherwise with markers of lower patient acuity. These findings inform quality improvement efforts aimed at improving pediatric transition to outpatient care after an ED encounter.
Genotyping strategies for detecting CRISPR mutations in polyploid species: a case study-based approach in hexaploid wheat
Authors: Gupta Ajay , Li Wanlong 
Published: November 2021

AbstractAs a versatile tool for genome engineering, CRISPR-Cas9 has been revolutionizing the field of molecular biology, biotechnology, and crop improvement. By precisely targeting pre-selected genomic sites, CRISPR-Cas9 primarily induces insertions or deletions (indels) of variable size. Despite the significant advance in the technology per se, detecting these indels is the major and difficult part of the CRISPR program in polyploid species, like wheat, with relatively low mutation rates. A plethora of methods are available for detecting mutations, but no method is perfect for all mutation types. In this case study, we demonstrated a new, protocol for capturing length polymorphism from small indels using a nested PCR approach. This new method is tractable, efficient, and cost-effective in detecting and genotyping indels >3-bp. We also discussed the major genotyping platforms used in our wheat CRISPR projects, such as mismatch cleavage assay, restriction enzyme assay, ribonucleoprotein assay, and Sanger sequencing, for their advantages and pitfalls in wheat CRISPR mutation detection.
A method to estimate the cellular composition of the mouse brain from heterogeneous datasets
Authors: Rodarie Dimitri , Verasztó Csaba , Roussel Yann , Reimann Michael , Keller Daniel , Ramaswamy Srikanth , Markram Henry , Gewaltig Marc-Oliver 
Published: November 2021

AbstractThe mouse brain contains a rich diversity of inhibitory neuron types that have been characterized by their patterns of gene expression. However, it is still unclear how these cell types are distributed across the mouse brain. We developed a computational method to estimate the densities of different inhibitory neuron types across the mouse brain. Our method allows the unbiased integration of diverse and disparate datasets into one framework to predict inhibitory neuron densities for uncharted brain regions. We constrained our estimates based on previously computed brain-wide neuron densities, gene expression data from in situ hybridization image stacks together with a wide range of values reported in the literature. Using constrained optimization, we derived coherent estimates of cell densities for the different inhibitory neuron types. We estimate that 20.3% of all neurons in the mouse brain are inhibitory. Among all inhibitory neurons, 18% predominantly express parvalbumin (PV), 16% express somatostatin (SST), 3% express vasoactive intestinal peptide (VIP), and the remainder 63% belong to the residual GABAergic population. We find that our density estimations improve as more literature values are integrated. Our pipeline is extensible, allowing new cell types or data to be integrated as they become available. The data, algorithms, software, and results of our pipeline are publicly available and update the Blue Brain Cell Atlas. This work therefore leverages the research community to collectively converge on the numbers of each cell type in each brain region.Author summaryObtaining a global understanding of the cellular composition of the brain is a very complex task, not only because of the great variability that exists between reports of similar counts but also because of the numerous brain regions and cell types that make up the brain. Previously, we presented a model of a cell atlas, which provided an estimate of the densities of neurons, glia and their subtypes for each region in the mouse brain. Here, we describe an extension of this model to include more inhibitory neuron types. We collected estimates of inhibitory neuron counts from literature and built a framework to combine them into a consistent cell atlas. Using brain slice images, we also estimated inhibitory neuron density in regions where no literature data are available. We estimated that in the mouse brain 20.3% of all neurons are inhibitory. Among all inhibitory neurons, 18% predominantly express parvalbumin (PV), 16% express somatostatin (SST), 3% express vasoactive intestinal peptide (VIP), and the remainder 63% belong to the residual GABAergic population.Our approach can be further extended to any other cell type and provides a resource to build tissue-level models of the rodent brain.
Humans can track but fail to predict accelerating objects
Authors: Kreyenmeier Philipp , Kämmer Luca , Fooken Jolande , Spering Miriam 
Published: November 2021

AbstractObjects in our visual environment often move unpredictably and can suddenly speed up or slow down. The ability to account for acceleration when interacting with moving objects can be critical for survival. Here, we investigate how human observers track an accelerating target with their eyes and predict its time of reappearance after a temporal occlusion by making an interceptive hand movement. Before occlusion, the target was initially visible and accelerated for a brief period. We tested how observers integrated target motion information by comparing three alternative models that predicted time-to-contact (TTC) based on the (1) final target velocity sample before occlusion, (2) average target velocity before occlusion, or (3) target acceleration. We show that visually-guided smooth pursuit eye movements reliably reflect target acceleration prior to occlusion. However, systematic saccade and manual interception timing errors reveal an inability to consider acceleration when predicting TTC. Interception timing is best described by the final velocity model that relies on extrapolating the last available velocity sample before occlusion. These findings provide compelling evidence for differential acceleration integration mechanisms in vision-guided eye movements and prediction-guided interception and a mechanistic explanation for the function and failure of interactions with accelerating objects.
A deep learning framework for inference of single-trial neural population dynamics from calcium imaging with sub-frame temporal resolution
Authors: Zhu Feng , Grier Harrison A. , Tandon Raghav , Cai Changjia , Agarwal Anjali , Giovannucci Andrea , Kaufman Matthew T. , Pandarinath Chethan 
Published: November 2021

AbstractIn many brain areas, neural populations act as a coordinated network whose state is tied to behavior on a moment-by-moment basis and millisecond timescale. Two-photon (2p) calcium imaging is a powerful tool to probe network-scale computation, as it can measure the activity of many individual neurons, monitor multiple cortical layers simultaneously, and sample from identified cell types. However, estimating network state and dynamics from 2p measurements has proven challenging because of noise, inherent nonlinearities, and limitations on temporal resolution. Here we describe RADICaL, a deep learning method to overcome these limitations at the population level. RADICaL extends methods that exploit dynamics in spiking activity for application to deconvolved calcium signals, whose statistics and temporal dynamics are quite distinct from electrophysiologically-recorded spikes. It incorporates a novel network training strategy that capitalizes on the timing of 2p sampling to recover network dynamics with high temporal precision. In synthetic tests, RADICaL infers network state more accurately than previous methods, particularly for high-frequency components. In real 2p recordings from sensorimotor areas in mice performing a “water grab” task, RADICaL infers network state with close correspondence to single-trial variations in behavior, and maintains high-quality inference even when neuronal populations are substantially reduced.
Anxiety attenuates learning advantages conferred by statistical stability and induces loss of volatility-attuning in brain activity
Authors: Rowe Elise G. , Harris Clare D. , Dzafic Ilvana , Garrido Marta I. 
Published: November 2021

ABSTRACTAnxiety can alter an individual’s perception of their external sensory environment. Previous studies suggest that anxiety can increase the magnitude of neural responses to unexpected (or surprising) stimuli. Additionally, surprise responses are reported to be boosted during stable compared to volatile environments. Few studies, however, have examined how learning is impacted by both threat and volatility. To investigate these effects, we used threat-of-shock to transiently increase subjective anxiety in healthy adults during an auditory oddball task, in which the regularity could be stable or volatile, while undergoing functional Magnetic Resonance Imaging (fMRI) scanning. We then used Bayesian Model Selection (BMS) mapping to pinpoint the brain areas where different models of anxiety displayed the highest evidence. Behaviourally, we found that threat-of-shock eliminated the accuracy advantage conferred by environmental stability over volatility in the task at hand. Neurally, we found that threat-of-shock led to both attenuation and loss of volatility-attuning of neural activity evoked by surprising sounds across most subcortical and limbic brain regions including the thalamus, basal ganglia, claustrum, insula, anterior cingulate, hippocampal gyrus and also the superior temporal gyrus. Conversely, within two small clusters in the left medial frontal gyrus and extrastriate area, threat-of-shock boosted the neural activity (relative to the safe and volatile condition) to the levels observed during the safe and stable condition, while also inducing a loss of volatility-attuning. Taken together, our findings suggest that threat eliminates the learning advantage conferred by statistical stability compared to volatility. Thus, we propose that anxiety disrupts behavioural adaptation to environmental statistics, and that multiple subcortical and limbic regions are implicated in this process.
Immunogenomic, single-cell and spatial dissection of CD8+T cell exhaustion reveals critical determinants of cancer immunotherapy
Authors: Naulaerts Stefan , Borras Daniel M , Martinez Asier Antoranz , Messiaen Julie , Van Herck Yannick , Gelens Lendert , Venken Tom , Vanmeerbeek Isaure , More Sanket , Sprooten Jenny , Bechter Oliver , Bergers Gabriele , Liston Adrian , De Vleeschouwer Steven , Van Den Eynde Benoit J , Lambrechts Diether , Borst Jannie , Bosisio Francesca , Tejpar Sabine , De Smet Frederik , Garg Abhishek D 
Published: November 2021

ABSTRACTTumoural-CD8+T cells exhibit exhausted or dysfunctional states. Contrary to immunotherapy-responsive exhausted-CD8+T cells, the clinical features of dysfunctional-CD8+T cells are disputed. Hence, we conducted large-scale multi-omics and multi-dimensional mapping of CD8+T cell-states across multiple cancer patient-cohorts. This identified tumour-specific continuum of CD8+T cell-states across 6 human cancers, partly imprinted by organ-specific immuno-modulatory niches. Herein, melanoma and glioblastoma enriched prototypical exhausted (CD8+TEXT) and severely-dysfunctional (CD8+TSDF) states, respectively. Contrary to CD8+TEXT, CD8+TSDF displayed transcriptomic and epigenetic effector/cytolytic dysfunctions, and dysregulated effector/memory single-cell trajectories, culminating into maladaptive prodeath stress and cell-cycle defects. Suboptimal antigen-priming underscored CD8+TSDF, which was distinct from immune-checkpoints “rich” CD8+TEXT, reflecting chronic antigen-stimulation. Continuum variation also existed on tumour spatial-level, with convergent (CD8+TEXT-supportive vascular regions) and divergent features (dysfunctional CD4+T::CD8+TSDFcell-to-cell interactions) between melanoma and glioblastoma. Globally, IFNγ-IL2 disparities, paucity of intra-tumoural CD4+/CD8+T cells, and myeloid TGFβ/wound healing responses, distinguished CD8+TSDF-landscape. Within immuno-oncology clinical-trials, anti-PD1 immunotherapy failed to “reinvigorate” CD8+TSDF-landscape, and instead facilitated effector-dysfunction and TGFβ/wound healing. However, cellular immunotherapies (dendritic cell-vaccines, adoptive T-cell therapy) ameliorated assorted CD8+TSDF-landscape disparities, highlighting a roadmap for anti-glioblastoma multimodal-immunotherapy. Collectively, our study comprehensively expands clinical-knowledge on CD8+T cell-exhaustion and suggests that tumour-specific, pre-existing CD8+TEXT/TSDF-states, determine immunotherapy-responses.
Ion-bridges and lipids drive aggregation of same-charge nanoparticles on lipid membranes
Authors: Lavagna Enrico , Bochicchio Davide , De Marco Anna L. , Güven Zekiye P. , Stellacci Francesco , Rossi Giulia 
Published: November 2021

ABSTRACTThe control of the aggregation of biomedical nanoparticles (NP) in physiological conditions is crucial as clustering may change completely the way they interact with the biological environment. Here we show that Au nanoparticles, functionalized by an anionic, amphiphilic shell, spontaneously aggregate in fluid zwitterionic lipid bilayers. We use Molecular Dynamics and enhanced sampling techniques to disentangle the short-range and long-range driving forces of aggregation. At short inter-particle distances, ion-mediated, charge-charge interactions (ion bridging) stabilize the formation of large NP aggregates, as confirmed by cryo-electron microscopy. Lipid depletion and membrane curvature are the main membrane deformations driving long-range NP-NP attraction. Ion bridging, lipid depletion, and membrane curvature stem from the configurational flexibility of the nanoparticle shell. Our simulations show, more in general, that the aggregation of same-charge membrane inclusions can be expected as a result of intrinsically nanoscale effects taking place at the NP-NP and NP-bilayer soft interfaces.