Miracle-dz/UniFAR-FTUs huggingface dataset:
Expertise Modulates Students’ Perception of Pain From a Self-Perspective: Quasi-Experimental Study

Background Perception of stimuli presented in a virtual dentistry environment affects regions of the brain that are related to pain perception. Objective We investigated whether neural correlates of virtual pain perception are affected by education in dentistry. Methods In this functional magnetic resonance imaging study, a sample of 20 dental students and 20 age-matched controls viewed and listened to video clips presenting a dental treatment from the first‐person perspective. An anxiety questionnaire was used to assess the level of dental anxiety. Neural correlates of pain perception were investigated through classic general linear model analysis and in-house classification methods. Results Dental students and naïve controls exhibited similar anxiety levels for invasive stimuli. Invasive dentistry scenes evoked a less affective component of pain in dental students compared with naïve controls (P<.001). Reduced affective pain perception went along with suppressed brain activity in pain matrix regions including the insula, anterior cingulate cortex, and basal ganglia. Furthermore, a substantial reduction of brain activity was observed in motor-related regions, particularly the supplementary motor area, premotor cortex, and basal ganglia. Within this context, a classifier analysis based on neural activity in the nucleus lentiformis could identify dental students and controls on the individual subject level in 85% of the cases (34 out of 40 participants, sensitivity=90%, specificity=80%). Conclusions Virtual dental treatment activates pain-related brain regions in controls. By contrast, dental students suppress affective and motor-related aspects of pain. We speculate that dental students learn to control motoric aspects of pain perception during their education because it is a prerequisite for the professional manual treatment of patients. We discuss that a specific set of learning mechanisms might affect perceived self-efficacy of dental students, which in turn might reduce their affective component of pain perception.
Differential radio-adaptive responses in BALB/c and C57BL/6 mice: pivotal role of calcium and nitric oxide signalling

Abstract Purpose: Our earlier studies demonstrated that transient radio-adaptive responses (RAR) in BALB/c mice were due to MAPK hyperactivation. The objective of this study was to determine the time duration of this low dose induced MAPK activation in BALB/c mice and to find out if similar adaptive responses are observed in C57BL/6 mice. Materials and methods: Mice were irradiated with 0.1 Gy priming dose (PD), 2 Gy challenge dose (CD) with an interval of 4 h (P + CD) and radiation induced immunosuppression in splenic lymphocytes was monitored as the endpoint for RAR. Results: Time kinetics following 0.1 Gy demonstrated persistence of MAPK hyperactivation till 48 h. Similar experiments in C57BL/6 mice indicated absence of RAR at 24 h following CD, in spite of MAPK activation which was also confirmed by time kinetics. Therefore, upstream activators of MAPK, viz., reactive oxygen and nitrogen species (ROS, RNS) and calcium levels were estimated. There was increased intracellular calcium (Ca2+) and nitric oxide (NO) in BALB/c and an increase in intracellular ROS in C57BL/6 mice 24 h after PD. Inhibition of NO and calcium chelation abrogated RAR in BALB/c mice. In vitro treatment of spleen cells with combination of NO donor and Ca2+ ionophore mimicked the effect of PD and induced adaptive response after 2 Gy not only in BALB/c but also in C57BL/6 mice confirming their crucial role in RAR. Conclusions: These results suggest that low dose induced differential induction of Ca2+ and NO signaling along with MAPK was responsible for contrasting RAR with respect to immune system of BALB/c and C57BL/6 mice. Abbreviations [3H]-TdR: 3H-methyl-thymidine; BAPTA: 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid; CD: Challenge Dose; CFSE: Carboxy Fluorescein Succinamidyl Ester; on A: Concanavalin A; DAF-FM: 4-amino-5-methylamino-2′,7′-difluorescein; DCF-DA: 2’,7’-dichlorofluorescein diacetate; DSB: Double Strand Break; ELISA: Enzyme Linked ImmunoSorbent Assay; ERK: Extracellular signal-Regulated protein Kinase; FBS: Fetal Bovine Serum; HIF-1A: Hypoxia-Inducible Factor 1-alpha; LDR: Low Dose Radiation; MAPK: Mitogen Activated Protein Kinase; MAPKK/MKK: MAPK Kinase; MAPKKK: MAPK Kinase Kinase; NO: Nitric Oxide; NOS: Nitric Oxide Synthase; P + CD: Priming + Challenge dose; PBS: Phosphate Buffered Saline; PBST: Phosphate Buffered Saline-Tween 20; PD: Priming Dose; PI3K: Phosphatidyl Inositol 3-Kinase; PKC: Protein Kinase C; RAR: Radio Adaptive Response; RNS: Reactive Nitrogen Species; ROS: Reactive Oxygen Species; RPMI-1640: Roswell Park Memorial Institute-1640 medium; SAPK/JNK: Stress-Activated Protein Kinase/ c-Jun NH2-terminal Kinase; SEM: Standard Error of Mean; SNAP: S-nitro amino penicillamine; TP53: Tumor Protein 53; γ-H2AX: Gamma- H2A histone family member X; Th1: Type 1 helper T cell responses; Th2: Type 2 helper T cell responses
Coincidence Detection within the Excitable Rat Olfactory Bulb Granule Cell Spines

In the mammalian olfactory bulb, the inhibitory axonless granule cells (GCs) feature reciprocal synapses that interconnect them with the principal neurons of the bulb, mitral, and tufted cells. These synapses are located within large excitable spines that can generate local action potentials (APs) upon synaptic input (“spine spike”). Moreover, GCs can fire global APs that propagate throughout the dendrite. Strikingly, local postsynaptic Ca2+ entry summates mostly linearly with Ca2+ entry due to coincident global APs generated by glomerular stimulation, although some underlying conductances should be inactivated. We investigated this phenomenon by constructing a compartmental GC model to simulate the pairing of local and global signals as a function of their temporal separation Δt. These simulations yield strongly sublinear summation of spine Ca2+ entry for the case of perfect coincidence Δt = 0 ms. Summation efficiency (SE) sharply rises for both positive and negative Δt. The SE reduction for coincident signals depends on the presence of voltage-gated Na+ channels in the spine head, while NMDARs are not essential. We experimentally validated the simulated SE in slices of juvenile rat brain (both sexes) by pairing two-photon uncaging of glutamate at spines and APs evoked by somatic current injection at various intervals Δt while imaging spine Ca2+ signals. Finally, the latencies of synaptically evoked global APs and EPSPs were found to correspond to Δt ≈ 10 ms, explaining the observed approximately linear summation of synaptic local and global signals. Our results provide additional evidence for the existence of the GC spine spike. SIGNIFICANCE STATEMENT Here we investigate the interaction of local synaptic inputs and global activation of a neuron by a backpropagating action potential within a dendritic spine with respect to local Ca2+ signaling. Our system of interest, the reciprocal spine of the olfactory bulb granule cell, is known to feature a special processing mode, namely, a synaptically triggered action potential that is restricted to the spine head. Therefore, coincidence detection of local and global signals follows different rules than in more conventional synapses. We unravel these rules using both simulations and experiments and find that signals coincident within ≈±7 ms around 0 ms result in sublinear summation of Ca2+ entry because of synaptic activation of voltage-gated Na+ channels within the spine.
Evolutionary pathways toward gigantism in sharks and rays

Through elasmobranch (sharks and rays) evolutionary history, gigantism evolved multiple times in phylogenetically distant species, some of which are now extinct. Interestingly, the world's largest elasmobranchs display two specializations found never to overlap: filter feeding and mesothermy. The contrasting lifestyles of elasmobranch giants provide an ideal case study to elucidate the evolutionary pathways leading to gigantism in the oceans. Here, we applied a phylogenetic approach to a global dataset of 459 taxa to study the evolution of elasmobranch gigantism. We found that filter feeders and mesotherms deviate from general relationships between trophic level and body size, and exhibit significantly larger sizes than ectothermic‐macropredators. We confirm that filter feeding arose multiple times during the Paleogene, and suggest the possibility of a single origin of mesothermy in the Cretaceous. Together, our results elucidate two main evolutionary pathways that enable gigantism: mesothermic and filter feeding. These pathways were followed by ancestrally large clades and facilitated extreme sizes through specializations for enhancing prey intake. Although a negligible percentage of ectothermic‐macropredators reach gigantic sizes, these species lack such specializations and are correspondingly constrained to the lower limits of gigantism. Importantly, the very adaptive strategies that enabled the evolution of the largest sharks can also confer high extinction susceptibility.
Valence and Core-Level X-ray Photoelectron Spectroscopy of a Liquid Ammonia Microjet

Photoelectron spectroscopy of microjets expanded into vacuum allows access to orbital energies for solute or solvent molecules in the liquid phase. Microjets of water, acetonitrile and alcohols have previously been studied; however, it has been unclear whether jets of low temperature molecular solvents could be realized. Here we demonstrate a stable 20 μm jet of liquid ammonia (−60 °C) in a vacuum, which we use to record both valence and core-level band photoelectron spectra using soft X-ray synchrotron radiation. Significant shifts from isolated ammonia in the gas-phase are observed, as is the liquid-phase photoelectron angular anisotropy. Comparisons with spectra of ammonia in clusters and the solid phase, as well as spectra for water in various phases potentially reveal how hydrogen bonding is reflected in the condensed phase electronic structure.
Building and Connecting: Family Strategies for Developing Social Support Networks for Adults With Down Syndrome

Being embedded in social networks is crucial for well-being and health. While this is particularly the case for people with Down syndrome (DS), our knowledge of how their support networks are developed is limited. This article investigates the role of family members in developing and maintaining the social support networks of their adult children with DS. Based on 29 interviews with family members, a grounded theory study was conducted. The Family Building and Connecting (BAC) framework was developed, which distinguishes a “building” and a “connecting” approach. The building approach includes strategies that rely on family members and close friends for building a support network for the person with DS. The connecting approach includes strategies that connect the person with DS to external and often professional resources and services. Distinguishing these approaches is important for future research and for strengthening the support networks of people with DS and their families.
The Development Process of Bipolar Bone Defects From Primary to Recurrent Instability in Shoulders With Traumatic Anterior Instability

Background: Recurrence of glenohumeral joint instability after primary traumatic anterior instability is not rare, and bipolar bone loss is one of the most critical factors for recurrent instability, but the development process of bipolar bone defects is still unclear. Purpose: To investigate the development process of bipolar bone defects from primary to recurrent instability among shoulders with traumatic anterior instability evaluated at least twice by computed tomography (CT). Study Design: Case series; Level of evidence, 4. Methods: There were 44 patients (47 shoulders) with recurrence after primary instability in which bone morphology was evaluated by 3-dimensional reconstructed CT at primary instability (initial CT) and after recurrence. As CT was performed 3 times for 3 shoulders including primary injury and the second episode of instability (first recurrence), there were 50 CT evaluations. Morphological changes between the initial CT evaluation at primary instability and the second CT evaluation at first recurrence were investigated for 25 shoulders, with the mean interval since initial CT being 9.8 months (range, 2-23 months). Changes between initial CT evaluation and final CT evaluation after ≥2 recurrences were also investigated for 25 shoulders, while the mean number of instability episodes including primary instability was 8.0 (range, 3-40) and the mean interval since initial CT was 18.5 months (range, 5-56 months). Results: At primary instability, the prevalence of Hill-Sachs lesions (66.0%) was almost double that of glenoid defects (34.0%), but their prevalence was different between shoulders with primary subluxation (42.3% and 23.8%, respectively) and those with primary dislocation (84.7% and 42.3%, respectively). After recurrence, glenoid defects became significantly more frequent (at first recurrence, 72%; after ≥2 recurrences, 76%), while Hill-Sachs lesions showed a smaller increase (88% and 80%, respectively), so there was no difference between the prevalence of the 2 lesions. The sizes of glenoid defects and Hill-Sachs lesions also enlarged after recurrence, and large bone defects were frequently recognized after recurrence. While bipolar bone loss was not so frequent at primary instability (29.8%), bipolar bone loss increased significantly after recurrence (at first recurrence, 72%; after ≥2 recurrences, 72%). All Hill-Sachs lesions were on track at primary instability, but off-track lesions were recognized in 3 of 47 shoulders (6.4%) after recurrence. Conclusion: In most shoulders with recurrent instability, a Hill-Sachs lesion developed first, followed by a glenoid defect, leading to bipolar bone loss. Off-track Hill-Sachs lesions were detected only after recurrence.
First prototyping of a dedicated PET system with the hemisphere detector arrangement

A strong demand is expected for high-sensitivity, high-resolution and low-cost brain positron emission tomography (PET) imaging for early diagnosis of dementia, as well as for general neuroscience studies. Therefore, we have proposed novel geometries of a hemisphere detector arrangement for high-sensitivity brain imaging, in which an add-on detector at the chin position or neck position helps in sensitivity uniformity improvement. In this study, we developed the first prototype system for proof-of-concept using four-layer depth-of-interaction detectors, each of which consisted of 16 × 16 × 4 Zr-doped GSO crystals with dimensions of 2.8 × 2.8 × 7.5 mm3 and a high-sensitivity 64-channel flat-panel photomultiplier tube. We used 47 detectors to form a hemisphere detector with a hemisphere shape of 25 cm inner diameter and 50 cm outer diameter, and we used seven detectors for each of the add-on detectors. The total detector number of 54 was about one-fourth that of a typical whole-body PET scanner. The hemisphere detector for the prototype system was realized by multiple rings having different numbers of detectors and a cross-shaped top detector unit covering the top. Performance evaluation showed uniform spatial resolutions of 3–4 mm by the filtered back-projection method. Imaging tests of a hot-rod phantom done with an iterative method were able to resolve 2.2 mm rods. Peak sensitivity was measured as more than 10% at a region near the top of the head, which was achieved with the help of the top detector unit. In addition, using the prototype system, we performed the first FDG clinical test with a healthy volunteer. The results showed that the proposed geometries had high potential for realizing high-sensitivity, high-resolution, and low-cost brain PET imaging. As for the add-on detector position, it was shown that the neck position resulted in higher sensitivity and wider field of view (FOV) than the chin position because the add-on detector at the neck position can be placed continuously to the hemisphere detector and close to the FOV.
Predicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment

Sparse data exist on the penetration of antiretrovirals into brain tissue. In this work, we present a framework to use efavirenz (EFV) pharmacokinetic (PK) data in plasma, cerebrospinal fluid (CSF), and brain tissue of eight rhesus macaques to predict brain tissue concentrations in HIV‐infected individuals. We then perform exposure‐response analysis with the model‐predicted EFV area under the concentration‐time curve (AUC) and neurocognitive scores collected from a group of 24 HIV‐infected participants. Adult rhesus macaques were dosed daily with 200 mg EFV (as part of a four‐drug regimen) for 10 days. Plasma was collected at 8 time points over 10 days and at necropsy, whereas CSF and brain tissue were collected at necropsy. In the clinical study, data were obtained from one paired plasma and CSF sample of participants prescribed EFV, and neuropsychological test evaluations were administered across 15 domains. PK modeling was performed using ADAPT version 5.0 Biomedical Simulation Resource, Los Angeles, CA) with the iterative two‐stage estimation method. An eight‐compartment model best described EFV distribution across the plasma, CSF, and brain tissue of rhesus macaques and humans. Model‐predicted median brain tissue concentrations in humans were 31 and 8,000 ng/mL, respectively. Model‐predicted brain tissue AUC was highly correlated with plasma AUC (γ = 0.99, P < 0.001) but not CSF AUC (γ = 0.34, P = 0.1) and did not show any relationship with neurocognitive scores (γ < 0.05, P > 0.05). This analysis provides an approach to estimate PK the brain tissue in order to perform PK/pharmacodynamic analyses at the target site.
Choice architecture interventions to improve diet and/or dietary behaviour by healthcare staff in high-income countries: a systematic review

Objectives We were commissioned by the behavioural insights team at Public Health England to synthesise the evidence on choice architecture interventions to increase healthy purchasing and/or consumption of food and drink by National Health Service (NHS) staff. Data sources MEDLINE, EMBASE, CINAHL, Cochrane Central register of Controlled Trials, PsycINFO, Applied Social Sciences Index and Abstracts and Web of Science were searched from inception until May 2017 and references were screened independently by two reviewers. Design A systematic review that included randomised experimental or intervention studies, interrupted time series and controlled before and after studies. Participants Healthcare staff of high-income countries. Intervention Choice architecture interventions that aimed to improve dietary purchasing and/or consumption (outcomes) of staff. Appraisal and synthesis Eligibility assessment, quality appraisal, data abstraction and analysis were completed by two reviewers. Quality appraisal of randomised trials was informed by the Cochrane Handbook, and the Risk of Bias Assessment Tool for Nonrandomized Studies was used for the remainder. Findings were narratively synthesised. Results Eighteen studies met the inclusion criteria. Five studies included multiple workplaces (including healthcare settings), 13 were conducted in healthcare settings only. Interventions in 10 studies were choice architecture only and 8 studies involved a complex intervention with a choice architecture element. Interventions involving a proximity element (making behavioural options easier or harder to engage with) appear to be frequently effective at changing behaviour. One study presented an effective sizing intervention. Labelling alone was generally not effective at changing purchasing behaviour. Interventions including an availability element were generally reported to be successful at changing behaviour but no included study examined this element alone. There was no strong evidence for the effect of pricing on purchasing or dietary intake. Conclusion Proximity, availability and sizing are choice architecture elements that are likely to be effective for NHS organisations. Trial registration number CRD42017064872.
Biomimetic mineralization using matrix vesicle nanofragments

Abstract In vitro synthesis of bone tissue has been paid attention in recent years; however, current methods to fabricate bone tissue are still ineffective due to some remaining gaps in the understanding of real in vivo bone formation process, and application of the knowledge in bone synthesis. Therefore, the objectives of this study were first, to perform a systematic and ultrastructural investigation of the initial mineral formation during intramembranous ossification of mouse calvaria from a material scientists' viewpoint, and to develop novel mineralization methods based on the in vivo findings. First, the very initial mineral deposition was found to occur at embryonic day E14.0 in mouse calvaria. Analysis of the initial bone formation process showed that it involved the following distinct steps: collagen secretion, matrix vesicle (MV) release, MV mineralization, MV rupture, and collagen fiber mineralization. Next, we performed in vitro mineralization experiments using MVs and hydrogel scaffolds. Intact MVs embedded in collagen gel did not mineralize, whereas, interestingly, MV nanofragments obtained by ultrasonication could promote rapid mineralization. These results indicate that mechanically ruptured MV membrane can be a promising material for in vitro bone tissue synthesis. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1021–1030, 2019.
In‐season adaptations to intense intermittent training and sprint interval training in sub‐elite football players

This study investigated the in‐season effect of intensified training comparing the efficacy of duration‐matched intense intermittent exercise training with sprint interval training in increasing intermittent running performance, sprint ability, and muscle content of proteins related to ion handling and metabolism in football players. After the first two weeks in the season, 22 sub‐elite football players completed either 10 weeks of intense intermittent training using the 10‐20‐30 training concept (10‐20‐30, n = 12) or sprint interval training (SIT, n = 10; work/rest ratio: 6‐s/54‐s) three times weekly, with a ~20% reduction in weekly training time. Before and after the intervention, players performed a Yo‐Yo intermittent recovery test level 1 (Yo‐Yo IR1) and a 30‐m sprint test. Furthermore, players had a muscle biopsy taken from the vastus lateralis. Yo‐Yo IR1 performance increased by 330 m (95%CI: 178‐482, P ≤ 0.01) in 10‐20‐30, whereas no change was observed in SIT. Sprint time did not change in 10‐20‐30 but decreased by 0.04 second (95%CI: 0.00‐0.09, P ≤ 0.05) in SIT. Muscle content of HADHA (24%, P ≤ 0.01), PDH‐E1α (40%, P ≤ 0.01), complex I‐V of the electron transport chain (ETC) (51%, P ≤ 0.01) and Na+, K+‐ATPase subunits α2 (33%, P ≤ 0.05) and β1 (27%, P ≤ 0.05) increased in 10‐20‐30, whereas content of DHPR (27%, P ≤ 0.01) and complex I‐V of the ETC (31%, P ≤ 0.05) increased in SIT. Intense intermittent training, combining short sprints and a high aerobic load, is superior to regular sprint interval training in increasing intense intermittent running performance during a Yo‐Yo IR1 test and muscle content of PDH‐E1α and HADHA in sub‐elite football players.