Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative Evaluation of Vascular Microcirculation Using Contrast-Enhanced Ultrasound Imaging In Rabbit Models of Choroidal Melanoma.

Purpose We investigated the application of contrast-enhanced ultrasound (CEUS) to quantify vascular perfusion in two animal models of choroidal melanoma. Methods B16F10 and choroidal melanoma cell line (OCM1) melanoma xenografts were implanted into the cyclodialysis cleft of rabbits' right eyes. Fundus photography, indocyanine green angiography (ICGA), B-mode ultrasound, and CEUS were used to examine the tumors. Standard vascular parameters of CEUS imaging were evaluated, including the area under the receiver operating characteristic curve (AUC), peak intensity (IMAX), mean transit time (mTT), rise time, and time to peak. Kruskal-Wallis tests followed by Nemenyi tests and Bonferroni corrections were used to analyze the findings. Results OCM1 and B16F10 animal models of choroidal melanoma were established. Tumor size was larger in the animals receiving B16F10 xenografts compared with the OCM1. Choroidal melanoma received a more abundant blood supply and had higher blood flow velocities than normal eye tissue. The animals receiving B16F10 xenografts had larger blood volume but smaller blood flow velocity compared with the OCM1 models. Vascular mimicry was present in seven of eight OCM1 tumors (87.5%). Growth and blood circulation patterns differed between OCM1 and B16F10 melanomas. Conclusions CEUS could be used to noninvasively dynamically, and safely detect the microcirculation patterns, quantify blood circulation volume, and velocity in ocular melanoma in animal models. The blood circulation patterns of two models were different in both qualitatively and quantitative analysis under CEUS and ICGA.
Synthesized zinc peroxide nanoparticles (ZnO2-NPs): a novel antimicrobial, anti-elastase, anti-keratinase, and anti-inflammatory approach toward polymicrobial burn wounds

Increasing of multidrug resistance (MDR) remains an intractable challenge for burn patients. Innovative nanomaterials are also in high demand for the development of new antimicrobial biomaterials that inevitably have opened new therapeutic horizons in medical approaches and lead to many efforts for synthesizing new metal oxide nanoparticles (NPs) for better control of the MDR associated with the polymicrobial burn wounds. Recently, it seems that metal oxides can truly be considered as highly efficient inorganic agents with antimicrobial properties. In this study, zinc peroxide NPs (ZnO2-NPs) were synthesized using the co-precipitation method. Synthesized ZnO2-NPs were characterized by X-ray diffraction, Fourier transformed infrared, transmission electron microscopy, thermogravimetric analysis, differential scanning calorimetry, and ultraviolet-visible spectroscopy. The characterization techniques revealed synthesis of the pure phase of non-agglomerated ZnO2-NPs having sizes in the range of 15–25 nm with a transition temperature of 211°C. Antimicrobial activity of ZnO2-NPs was determined against MDR Pseudomonas aeruginosa (PA) and Aspergillus niger (AN) strains isolated from burn wound infections. Both strains, PA6 and AN4, were found to be more susceptible strains to ZnO2-NPs. In addition, a significant decrease in elastase and keratinase activities was recorded with increased concentrations of ZnO2-NPs until 200 µg/mL. ZnO2-NPs revealed a significant anti-inflammatory activity against PA6 and AN4 strains as demonstrated by membrane stabilization, albumin denaturation, and proteinase inhibition. Moreover, the results of in vivo histopathology assessment confirmed the potential role of ZnO2-NPs in the improvement of skin wound healing in the experimental animal models. Clearly, the synthesized ZnO2-NPs have demonstrated a competitive capability as antimicrobial, anti-elastase, anti-keratinase, and anti-inflammatory candidates, suggesting that the ZnO2-NPs are promising metal oxides that are potentially valued for biomedical applications.
Auditory Hallucinations as Translational Psychiatry: Evidence from Magnetic Resonance Imaging

In this invited review article, I present a translational perspective and overview of our research on auditory hallucinations in schizophrenia at the University of Bergen, Norway, with a focus on the neuronal mechanisms underlying the phenomenology of experiencing “hearing voices”. An auditory verbal hallucination (i.e. hearing a voice) is defined as a sensory experience in the absence of a corresponding external sensory source that could explain the phenomenological experience. I suggest a general frame or scheme for the study of auditory verbal hallucinations, called Levels of Explanation. Using a Levels of Explanation approach, mental phenomena can be described and explained at different levels (cultural, clinical, cognitive, brain-imaging, cellular and molecular). Another way of saying this is that, to advance knowledge in a research field, it is not only necessary to replicate findings, but also to show how evidence obtained with one method, and at one level of explanation, converges with evidence obtained with another method at another level. To achieve breakthroughs in our understanding of auditory verbal hallucinations, we have to advance vertically through the various levels, rather than the more common approach of staying at our favourite level and advancing horizontally (e.g., more advanced techniques and data acquisition analyses). The horizontal expansion will, however, not advance a deeper understanding of how an auditory verbal hallucination spontaneously starts and stops. Finally, I present data from the clinical, cognitive, brain-imaging, and cellular levels, where data from one level validate and support data at another level, called converging of evidence. Using a translational approach, the current status of auditory verbal hallucinations is that they implicate speech perception areas in the left temporal lobe, impairing perception of and attention to external sounds. Preliminary results also show that amygdala is implicated in the emotional «colouring» of the voices and that excitatory neurotransmitters might be involved. What we do not know is why hallucinatory episodes occur spontaneously, why they fluctuate over time, and what makes them spontaneously stop. Moreover, is voice hearing a category or dimension in its own right, independent of diagnosis, and why is the auditory modality predominantly implicated in psychotic disorders, while the visual modality dominates in, for example, neurological diseases?
Physiological Stress Mediates the Honesty of Social Signals

Background Extravagant ornaments used as social signals evolved to advertise their bearers' quality. The Immunocompetence Handicap Hypothesis proposes that testosterone-dependent ornaments reliably signal health and parasite resistance; however, empirical studies have shown mixed support. Alternatively, immune function and parasite resistance may be indirectly or directly related to glucocorticoid stress hormones. We propose that an understanding of the interplay between the individual and its environment, particularly how they cope with stressors, is crucial for understanding the honesty of social signals. Methodology/Principal Findings We analyzed corticosterone deposited in growing feathers as an integrated measure of hypothalamic-pituitary-adrenal activity in a wild territorial bird, the red grouse Lagopus lagopus scoticus. We manipulated two key, interrelated components, parasites and testosterone, which influence both ornamentation and fitness. Birds were initially purged of parasites, and later challenged with parasites or not, while at the same time being given testosterone or control implants, using a factorial experimental design. At the treatment level, testosterone enhanced ornamentation, while parasites reduced it, but only in males not implanted with testosterone. Among individuals, the degree to which both parasites and testosterone had an effect was strongly dependent on the amount of corticosterone in the feather grown during the experiment. The more stressors birds had experienced (i.e., higher corticosterone), the more parasites developed, and the less testosterone enhanced ornamentation. Conclusions/Significance With this unique focus on the individual, and a novel, integrative, measure of response to stressors, we show that ornamentation is ultimately a product of the cumulative physiological response to environmental challenges. These findings lead toward a more realistic concept of honesty in signaling as well as a broader discussion of the concept of stress.
Effects of Psychiatric Comorbidity in Immune-Mediated Inflammatory Disease: Protocol for a Prospective Study

Background Immune-mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), multiple sclerosis (MS), and rheumatoid arthritis (RA), are highly prevalent in Canada and the United States and result in substantial personal and societal burden. The prevalence of psychiatric comorbidities, primarily depression and anxiety, in IMID exceeds those in the general population by two- to threefold, but remains underdiagnosed and undertreated. Furthermore, the effects of psychiatric comorbidity on IMID are not well understood. Objective The objectives of this study were (1) to compare health-related quality of life and work ability in persons with IMID and psychiatric comorbidity with those of persons with IMID without psychiatric comorbidity and with those of persons with depression and anxiety disorders alone, and (2) to validate existing case identification tools for depression and anxiety in persons with IMID to facilitate improved identification of depression and anxiety by clinicians. To achieve these objectives, we designed a prospective 3-year longitudinal study. In this paper, we aim to describe the study rationale and design and the characteristics of study participants. Methods Between November 2014 and July 2016, we recruited 982 individuals from multiple clinic and community sources; 18 were withdrawn due to protocol violations. Results The final study sample included 247 participants with IBD, 255 with MS, 154 with RA, and 308 with depression or anxiety. The majority were white, with the proportion ranging from 85.4% (IBD [210/246]; MS [217/254]) to 74.5% (114/153, RA; P=.01). There was a female predominance in all groups, which was highest in the RA cohort (84.4%, 130/154) and least marked in the IBD cohort (62.7%, 155/247). Participants with depression or anxiety were more likely to be single (36.0%, 111/308) than participants in any other group (11.8% [30/255]-22.7% [56/247], P<.001). Conclusions This paper presents the rationale for this study, describes study procedures, and characterizes the cohort enrolled. Ultimately, the aim is improved care for individuals affected by IMID.
Remapping cortical modulation for electrocorticographic brain–computer interfaces: a somatotopy-based approach in individuals with upper-limb paralysis

Objective. Brain–computer interface (BCI) technology aims to provide individuals with paralysis a means to restore function. Electrocorticography (ECoG) uses disc electrodes placed on either the surface of the dura or the cortex to record field potential activity. ECoG has been proposed as a viable neural recording modality for BCI systems, potentially providing stable, long-term recordings of cortical activity with high spatial and temporal resolution. Previously we have demonstrated that a subject with spinal cord injury (SCI) could control an ECoG-based BCI system with up to three degrees of freedom (Wang et al 2013 PLoS One). Here, we expand upon these findings by including brain-control results from two additional subjects with upper-limb paralysis due to amyotrophic lateral sclerosis and brachial plexus injury, and investigate the potential of motor and somatosensory cortical areas to enable BCI control. Approach. Individuals were implanted with high-density ECoG electrode grids over sensorimotor cortical areas for less than 30 d. Subjects were trained to control a BCI by employing a somatotopic control strategy where high-gamma activity from attempted arm and hand movements drove the velocity of a cursor. Main results. Participants were capable of generating robust cortical modulation that was differentiable across attempted arm and hand movements of their paralyzed limb. Furthermore, all subjects were capable of voluntarily modulating this activity to control movement of a computer cursor with up to three degrees of freedom using the somatotopic control strategy. Additionally, for those subjects with electrode coverage of somatosensory cortex, we found that somatosensory cortex was capable of supporting ECoG-based BCI control. Significance. These results demonstrate the feasibility of ECoG-based BCI systems for individuals with paralysis as well as highlight some of the key challenges that must be overcome before such systems are translated to the clinical realm. ClinicalTrials.gov Identifier: NCT01393444.
Simulation of the Effective of Friction on the Deformation in Equal Channel Angular Pressing (ECAP)

A influence of friction on the deformation behavior and strain homogeneity during ECAP has been studied by conducting 2D and 3D finite element simulations for a range of friction conditions m = 0 – 0.2. The deformation was more uniform in central steady zone as compared to the ends of the sample. The calculated ram load was higher in 3D simulations than 2D simulations. For a frictionless condition, the ram load was similar in both 2D and 3D simulations. Keywords: ECAP, SPD, FEM, Coulomb friction model, friction condition, ram load.
Taking it easy when playing ultimatum game with a Down syndrome proposer: Effects on behavior and medial frontal negativity

ABSTRACT The ultimatum game (UG) is an endowment sharing game in which a proposer suggests a division of an asset to a recipient, who must accept or reject it. Economic studies showed that despite recipients usually rejecting unfair offers, perception and reaction to unfairness are highly dependent on who is the proposer. Event-related potentials (ERPs) commonly detected in UG games are the medial frontal negativity (MFN), a component detected in recipients facing unfair offers, and the P300, a component related to attentional and memory processes. Given this, we aimed to investigate the behavioral and ERP responses of healthy people playing the UG game with Down syndrome (DS) and typical development (TD) proposers. Nineteen subjects participated in this study. The UG behavioral data were similar to previous studies. ERP analysis showed no MFN in participants facing unfair offers. A higher P300 amplitude was detected when participants faced fair offers from TD compared to DS fair offers. We also found a positive correlation between P300 amplitude for TD offers and self-esteem scale score. Together these findings indicate that insertion of an atypical player in the UG led to changes in participants’ perception and expectancy of the game.
TIM-4 is differentially expressed in the distinct subsets of dendritic cells in skin and skin-draining lymph nodes and controls skin Langerhans cell homeostasis

T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on dendritic cells (DC) and macrophages, plays an essential role in regulating immune responses. Langerhans cells (LC), which are the sole DC subpopulation residing at the epidermis, are potent mediators of immune surveillance and tolerance. However, the significance of TIM-4 on epidermal LCs, along with other cutaneous DCs, remains totally unexplored. For the first time, we discovered that epidermal LCs expressed TIM-4 and displayed an increased level of TIM-4 expression upon migration. We also found that dermal CD207+ DCs and lymph node (LN) resident CD207−CD4+ DCs highly expressed TIM-4, while dermal CD207− DCs and LN CD207−CD4− DCs had limited TIM-4 expressions. Using TIM-4-deficient mice, we further demonstrated that loss of TIM-4 significantly upregulated the frequencies of epidermal LCs and LN resident CD207−CD4+ DCs. In spite of this, the epidermal LCs of TIM-4-deficient mice displayed normal phagocytic and migratory abilities, comparable maturation status upon the stimulation as well as normal repopulation under the inflamed state. Moreover, lack of TIM-4 did not affect dinitrofluorobenzene-induced contact hypersensitivity response. In conclusion, our results indicated that TIM-4 was differentially expressed in the distinct subsets of DCs in skin and skin-draining LNs, and specifically regulated epidermal LC and LN CD207−CD4+ DC homeostasis.
Universal 2 total wrist arthroplasty: high satisfaction but high complication rates

The Universal 2 total wrist arthroplasty is intended to alleviate wrist pain and restore function. There is limited evidence regarding its success and safety. We report outcomes in 48 wrists of 46 patients with Universal 2 arthroplasty between 2006 and 2014. We recorded range of motion of the operated wrist, patient satisfaction, complication and revision rates, and radiological appearances of the wrists with mean follow-up of 7 years (3.5 to 11 years). We found a significant improvement in DASH scores after surgery, with active range of wrist motion being 33° flexion and 24° extension. Thirty-nine patients would undergo the procedure again if he had similar wrist problems. Twenty-three patients had loosening of at least one component of the implant. Complications were found in 13 wrists; seven underwent revision. We conclude that the Universal 2 arthroplasty produces significant improvements in DASH scores and high levels of satisfaction of the patients. However, the surgery has a high complication rate. Level of evidence: IV
Skull base erosion and associated complications in sphenoid sinus fungal balls

Background Sphenoid sinus fungal balls (SSFB) are rare entities that can result in serious orbital and intracranial complications. There are few published reports of complications that result from SSFB. Objective To review the incidence of skull base erosion and orbital or intracranial complications in patients who present with SSFB. Methods A retrospective review was performed of all the patients with SSFB who were treated at the Massachusetts Eye and Ear Infirmary from 2006 to 2014. Presenting clinical data, radiology, operative reports, pathology, and postoperative course were reviewed. Results Forty-three patients with SSFB were identified. Demographic data were compared between patients with (39.5%) and those without (61.5%) skull base erosion. Two patients underwent emergent surgery for acute complications of SSFB (one patient with blindness, one patient who had a seizure). Both patients with acute complications had evidence of skull base erosion, whereas no patients with an intact skull base developed an orbital or intracranial complication (p = 0.15). All the patients were surgically managed via an endoscopic approach. Conclusion SSFBs are rare but may cause significant skull base erosion and potentially severe orbital and intracranial complications if not treated appropriately. Endoscopic sphenoidotomy is effective in treating SSFB and should be performed emergently in patients who presented with associated complications.
Root hairs increase rhizosphere extension and carbon input to soil

Background and Aims Although it is commonly accepted that root exudation enhances plant-microbial interactions in the rhizosphere, experimental data on the spatial distribution of exudates are scarce. Our hypothesis was that root hairs exude organic substances to enlarge the rhizosphere farther from the root surface. Methods Barley (Hordeum vulgare 'Pallas' - wild type) and its root-hairless mutant (brb) were grown in rhizoboxes and labelled with 14CO2. A filter paper was placed on the soil surface to capture, image and quantify root exudates. Key Results Plants with root hairs allocated more carbon (C) to roots (wild type: 13 %; brb: 8 % of assimilated 14C) and to rhizosheaths (wild type: 1.2 %; brb: 0.2 %), while hairless plants allocated more C to shoots (wild type: 65 %; brb: 75 %). Root hairs increased the radial rhizosphere extension three-fold, from 0.5 to 1.5 mm. Total exudation on filter paper was three times greater for wild type plants compared to the hairless mutant. Conclusion Root hairs increase exudation and spatial rhizosphere extension, which probably enhance rhizosphere interactions and nutrient cycling in larger soil volumes. Root hairs may therefore be beneficial to plants under nutrient-limiting conditions. The greater C allocation below ground in the presence of root hairs may additionally foster C sequestration.
Placental Nano-vesicles Target to Specific Organs and Modulate Vascular Tone In Vivo

STUDY QUESTION How do nano-vesicles extruded from normal first trimester human placentae affect maternal vascular function? SUMMARY ANSWER Placental nano-vesicles affect the ability of systemic mesenteric arteries to undergo endothelium- and nitric oxide- (NO-) dependent vasodilation in vivo in pregnant mice. WHAT IS KNOWN ALREADY Dramatic cardiovascular adaptations occur during human pregnancy, including a substantial decrease in total peripheral resistance in the first trimester. The human placenta constantly extrudes extracellular vesicles that can enter the maternal circulation and these vesicles may play an important role in feto-maternal communication. STUDY DESIGN, SIZE, DURATION Human placental nano-vesicles were administered into CD1 mice via a tail vein and their localization and vascular effects at 30 min and 24 h post-injection were investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS Nano-vesicles from normal first trimester human placentae were collected and administered into pregnant (D12.5) or non-pregnant female mice. After either 30 min or 24 h of exposure, all major organs were dissected for imaging (n = 7 at each time point) while uterine and mesenteric arteries were dissected for wire myography (n = 6 at each time point). Additional in vitro studies using HMEC-1 endothelial cells were also conducted to investigate the kinetics of interaction between placental nano-vesicles and endothelial cells. MAIN RESULTS AND THE ROLE OF CHANCE Nano-vesicles from first trimester human placentae localized to the lungs, liver and kidneys 24 h after injection into pregnant mice (n = 7). Exposure of pregnant mice to placental nano-vesicles for 30 min in vivo increased the vasodilatory response of mesenteric arteries to acetylcholine, while exposure for 24 h had the opposite effect (P < 0.05, n = 6). These responses were prevented by L-NAME, an NO synthase inhibitor. Placental nano-vesicles did not affect the function of uterine arteries or mesenteric arteries from non-pregnant mice. Placental nano-vesicles rapidly interacted with endothelial cells via a combination of phagocytosis, endocytosis and cell surface binding in vitro. LARGE SCALE DATA N/A. LIMITATIONS REASONS FOR CAUTION As it is not ethical to administer labelled placental nano-vesicles to pregnant women, pregnant CD1 mice were used as a model of pregnancy. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to report the localization of placental nano-vesicles and their vascular effects in vivo. This work provides new insight into how the dramatic maternal cardiovascular adaptations to pregnancy may occur and indicates that placental extracellular vesicles may be important mediators of feto-maternal communication in a healthy pregnancy. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Faculty of Medical and Health Science (FMHS) School of Medicine PBRF research fund to L.W. C. M.T. is a recipient of a University of Auckland Health Research Doctoral Scholarship and the Freemasons Postgraduate Scholarship. No authors have any competing interests to disclose.