Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization of Ultrasound-Mediated Drug Delivery for Treatment of Onychomycosis.

BACKGROUND Onychomycosis is a fungal nail disorder that does not have a successful cure due to the poor permeability of topical anti-fungal drugs through the nail. This study utilizes ultrasound to increase the permeability of the nail to the topical drugs currently used in clinic. The first aim of this study was to optimize ultrasonic parameters within the temperature increase limits set by the American Institute of Ultrasound in Medicine (AIUM) and the British Medical Ultrasound Society (BMUS). The second aim of the study was to evaluate the optimized parameters for a cause of action of either cavitation (the creation of micrometer pores in the nail barrier) or acoustic streaming (a steady fluid motion which may help push the drug through the nail). METHODS Porcine and human nails are used in the five studies. PZFlex Modeling Software is used to model the temperature increase in the toe as a result of ultrasonic application and these results were used to develop the three parameters tested throughout the rest of the studies. The three parameters tested were 1 min of continuous ultrasonic application, 3 min of 50% ultrasonic application and 5 min of 50% ultrasonic application. In order to address the second aim of our research work, these three parameters were tested for the presence of streaming and cavitation. RESULTS At the three tested parameters, the most permeation of the nail occurs with 1 min of continuous application of ultrasound to the nail. It was also found that there was limited cavitation and significant streaming at all three parameters. This suggests that streaming may be the main mechanism-of-action in ultrasound-mediated drug delivery through the nail. CONCLUSION The parameter of 1 min of continuous ultrasonic testing will continue to be employed as the testing is moved to a rabbit model of onychomycosis.
Contraceptive Decision Making Among Latina Immigrants: Developing Theory-Based Survey Items

Background: Contraception is important for reproductive autonomy, yet many Latinas do not use contraception consistently despite research reporting a desire to do so. Factors varying in priority and value come into play during contraceptive decision making. When measuring these, relevant survey items may vary by populations. Aim: This study focused on developing an ethnically responsive, patient-centered, content-valid survey for measuring factors that influence contraceptive decision making among immigrant Latinas. Method: Nonpregnant self-identified Latinas ages 15 to 24 years in Baltimore, MD, were recruited from a family planning facility. Using the theory of planned behavior as a theoretical framework and prior formative research, initial survey items were drafted (Step 1). Content validation and cognitive interviewing procedures (Step 2 and Step 3) were used to develop final items. Results: Final items (27) were content-validated by the target population; items reflect important factors and relevant contexts affecting contraceptive decision making among Latinas in Baltimore. Discussion: These theory-based items provide an important contribution to the literature because they measure and explore factors related to contraceptive decision making in an understudied population. Providers might consider these factors during counseling to build patient-centered communication. These items might serve to measure responses to theory of planned behavior–based interventions designed to improve the contraceptive counseling of Latinas.
3D Shape Modeling and Analysis of Retinal Microvasculature in OCT-Angiography Images

3D optical coherence tomography angiography (OCT-A) is a novel and non-invasive imaging modality for analyzing retinal diseases. The studies of microvasculature in 2D en face projection images have been widely implemented, but comprehensive 3D analysis of OCT-A images with rich depth-resolved microvascular information is rarely considered. In this paper, we propose a robust, effective, and automatic 3D shape modeling framework to provide a high-quality 3D vessel representation and to preserve valuable 3D geometric and topological information for vessel analysis. Effective vessel enhancement and extraction steps by means of curvelet denoising and optimally oriented flux (OOF) filtering are first designed to produce 3D microvascular networks. Afterwards, a novel 3D data representation of OCT-A microvasculature is reconstructed via advanced mesh reconstruction techniques. Based on the 3D surfaces, shape analysis is established to extract novel shape-based microvascular area distortion via the Laplace-Beltrami eigen-projection. The extracted feature is integrated into a graph-cut segmentation system to categorize large vessels and small capillaries for more precise shape analysis. The proposed framework is validated on a dedicated repeated scan dataset including 260 volume images and shows high repeatability. Statistical analysis using the surface area biomarker is performed on small capillaries to avoid the effect of tailing artifact from large vessels. It shows significant differences ( $p< 0.001$ ) between DR stages on 100 subjects in a OCTA-DR dataset. The proposed shape modeling and analysis framework opens the possibility for further investigating OCT-A microvasculature in a new perspective.
Long‐term obesogenic diet and targeted deletion of potassium channel Kv1.3 have differing effects on voluntary exercise in mice

Voluntary exercise is frequently employed as an intervention for obesity. The voltage‐gated potassium channel Kv1.3 is also receiving attention as a therapeutic target for obesity, in addition to potential therapeutic capabilities for neuroinflammatory diseases. To investigate the combinatorial effects of these two therapies, we have compared the metabolic status and voluntary exercise behavior of both wild‐type mice and a transgenic line of mice that are genetic knockouts for Kv1.3 when provided with a running wheel and maintained on diets of differing fat content and caloric density. We tracked the metabolic parameters and wheel running behavior while maintaining the mice on their assigned treatment for 6 months. Wild‐type mice maintained on the fatty diet gain a significant amount of bodyweight and adipose tissue and display significantly impaired glucose tolerance, though all these effects were partially reduced with provision of a running wheel. Similar to previous studies, the Kv1.3‐null mice were resistant to obesity, increased adiposity, and impaired glucose tolerance. Both wild‐type and Kv1.3‐null mice maintained on the fatty diet displayed increased wheel running activity compared to control‐fed mice, which was caused primarily by a significant increase in the amount of time spent running as opposed to an increase in running velocity. Interestingly, the patterns of running behavior differed between wild‐type and Kv1.3‐null mice. Kv1.3‐null mice spent significantly less time running during the light phase and displayed a decrease in running 1–2 h before the onset of the light phase, seemingly in anticipation of the dark‐to‐light phase transition. These studies indicate that voluntary exercise combats metabolic maladies and running behavior is modified by both consumption of an obesogenic diet and deletion of the Kv1.3 channel.
Mass spectrometry-based methods for analysing the mitochondrial interactome in mammalian cells

Abstract Protein–protein interactions are essential biologic processes that occur at inter- and intracellular levels. To gain insight into the various complex cellular functions of these interactions, it is necessary to assess them under physiologic conditions. Recent advances in various proteomic technologies allow to investigate protein–protein interaction networks in living cells. The combination of proximity-dependent labelling and chemical cross-linking will greatly enhance our understanding of multi-protein complexes that are difficult to prepare, such as organelle-bound membrane proteins. In this review, we describe our current understanding of mass spectrometry-based proteomics mapping methods for elucidating organelle-bound membrane protein complexes in living cells, with a focus on protein–protein interactions in mitochondrial subcellular compartments.
The Good Enough Space in Art Therapy

This paper provides context for the zine, “The Good Enough Space”, printed in March 2015, distributed to students at Creative Arts Therapies Programs at Concordia University, and available online. The zine illustrates the fictionalized account of two art therapy interns in their second year practicum and presents some of the challenges they face creating consistency for their clients and conducting art therapy in the spaces provided at their practicum sites. Motivated by my experience of having to shift my expectations of the art therapy room and to learn to adapt to what was available to me, I was interested in finding out what was necessary to creating consistency for our clients in changing circumstances. This research explores the ideal art therapy space, art therapy in hospital settings, art therapy in school settings, positive therapist qualities, and affect regulation modeled in the client therapist relationship.
Self-reported sleep disturbances are associated with poorer cognitive performance in older adults with hypertension: a multi-parameter risk factor investigation

ABSTRACT Objectives: Given the evidence of multi-parameter risk factors in shaping cognitive outcomes in aging, including sleep, inflammation, cardiometabolism, and mood disorders, multidimensional investigations of their impact on cognition are warranted. We sought to determine the extent to which self-reported sleep disturbances, metabolic syndrome (MetS) factors, cellular inflammation, depressive symptomatology, and diminished physical mobility were associated with cognitive impairment and poorer cognitive performance. Design: This is a cross-sectional study. Setting: Participants with elevated, well-controlled blood pressure were recruited from the local community for a Tai Chi and healthy-aging intervention study. Participants: One hundred forty-five older adults (72.7 ± 7.9 years old; 66% female), 54 (37%) with evidence of cognitive impairment (CI) based on Montreal Cognitive Assessment (MoCA) score ≤24, underwent medical, psychological, and mood assessments. Measurements: CI and cognitive domain performance were assessed using the MoCA. Univariate correlations were computed to determine relationships between risk factors and cognitive outcomes. Bootstrapped logistic regression was used to determine significant predictors of CI risk and linear regression to explore cognitive domains affected by risk factors. Results: The CI group were slower on the mobility task, satisfied more MetS criteria, and reported poorer sleep than normocognitive individuals (all p < 0.05). Multivariate logistic regression indicated that sleep disturbances, but no other risk factors, predicted increased risk of evidence of CI (OR = 2.00, 95% CI: 1.26–4.87, 99% CI: 1.08–7.48). Further examination of MoCA cognitive subdomains revealed that sleep disturbances predicted poorer executive function (β = –0.26, 95% CI: –0.51 to –0.06, 99% CI: –0.61 to –0.02), with lesser effects on visuospatial performance (β = –0.20, 95% CI: –0.35 to –0.02, 99% CI: –0.39 to 0.03), and memory (β = –0.29, 95% CI: –0.66 to –0.01, 99% CI: –0.76 to 0.08). Conclusions: Our results indicate that the deleterious impact of self-reported sleep disturbances on cognitive performance was prominent over other risk factors and illustrate the importance of clinician evaluation of sleep in patients with or at risk of diminished cognitive performance. Future, longitudinal studies implementing a comprehensive neuropsychological battery and objective sleep measurement are warranted to further explore these associations.
On Robot Compliance: A Cerebellar Control Approach

The work presented here is a novel biological approach for the compliant control of a robotic arm in real time (RT). We integrate a spiking cerebellar network at the core of a feedback control loop performing torque-driven control. The spiking cerebellar controller provides torque commands allowing for accurate and coordinated arm movements. To compute these output motor commands, the spiking cerebellar controller receives the robot’s sensorial signals, the robot’s goal behavior, and an instructive signal. These input signals are translated into a set of evolving spiking patterns representing univocally a specific system state at every point of time. Spike-timing-dependent plasticity (STDP) is then supported, allowing for building adaptive control. The spiking cerebellar controller continuously adapts the torque commands provided to the robot from experience as STDP is deployed. Adaptive torque commands, in turn, help the spiking cerebellar controller to cope with built-in elastic elements within the robot’s actuators mimicking human muscles (inherently elastic). We propose a natural integration of a bioinspired control scheme, based on the cerebellum, with a compliant robot. We prove that our compliant approach outperforms the accuracy of the default factory-installed position control in a set of tasks used for addressing cerebellar motor behavior: controlling six degrees of freedom (DoF) in smooth movements, fast ballistic movements, and unstructured scenario compliant movements.
Molecular phylogeny and morphology reveal a new epiphytic species of Habenaria (Orchidaceae; Orchideae; Orchidinae) from Nepal

Habenaria is almost cosmopolitan in distribution having predominantly terrestrial orchids, however; a remarkable epiphytic species with some unique morphological characters was collected from Nepal. We conducted a molecular phylogeny of this unusual Habenaria species using nuclear (ITS) and chloroplast (matK, rbcl) DNA sequence regions to infer its systematic position. Our molecular analyses and morphological treatment recognized this newly collected plant as an undescribed species. This species is described here which is closely related to Habenaria plurifoliata but can be distinguished by having its multiple growing callus-shaped tuber, smaller stature with short stem, longer and wider oblanceolate leaves, peduncle with a foliaceous bract and only one sterile bract, lateral sepals oblong, obtuse, petal apex obtuse, lateral lobes of lip spreading upwards, spur not exceeding the ovary and pedicel.
Quantitative Assessment of Breast Density: Transmission Ultrasound is Comparable to Mammography with Tomosynthesis

Elevated breast density is among the strongest independent predictors of breast cancer. Breast density scores are critical inputs in models used to calculate a patient's lifetime risk of developing breast cancer. Today, the only FDA-cleared technology for assessing breast density uses mammography. An alternative modality for breast density quantification is 3D transmission ultrasound (TU). In this retrospective study, we compared automated breast density calculations derived from TU using quantitative breast density (QBD) and mammography with tomosynthesis using VolparaDensity 3.1 for 225 breasts. Pearson correlation coefficients (r) and intraclass correlation coefficients were compared. Subset analyses of extremely dense breasts, premenopausal, and postmenopausal breasts were also performed. Comparative analysis between radiologist-derived density assessment and objective automated scores was performed. Calculations from TU and mammography with tomosynthesis for breast density, total breast volume (TBV), and fibroglandular volume (FGV) were strongly correlated (r = 0.91, 0.92, and 0.67, respectively). We observed moderate absolute agreement for FGV and breast density, and strong absolute agreement for TBV. A subset of 56 extremely dense breasts showed similar trends, however with lower breast density agreement in the subset than in the full study. No significant difference existed in density correlation between premenopausal and postmenopausal breasts across modalities. QBD calculations from TU were strongly correlated with breast density scores from VolparaDensity. TU systematically measured higher FGV and breast density compared with mammography, and the difference increased with breast density. Impact: TU of the breast can accurately quantify breast density comparable with mammography with tomosynthesis.
Emerging phenotypes of sarcoidosis based on 18F-FDG PET/CT: a hierarchical cluster analysis

ABSTRACT Objectives: In sarcoidosis, the definition of organ involvement with traditional means appears laborious and somewhat controversial, and phenotyping by the above overlapping. 18F-FDG PET/CT defines disease extent by activity more precisely, and may result in a better understanding of sarcoidosis disease behavior and phenotypes expression. We hypothesized that 18F-FDG PET/CT could add in the phenotyping of sarcoidosis patients by unveiling in detail sites of involvement even in clinically and physiologically silent disease. Methods: This study was designed to investigate the role of 18F-FDG PET/CT in phenotyping sarcoidosis using cluster analysis by adding this new means in the routine work-up of 195 sarcoidosis patients of a single academic center. Results: 18F-FDG PET/CT succeeded to identify despite the random distribution of the disease, an ordered stratification into 4 phenotypes: I) thoracic nodal hilar-mediastinal, II) thoracic nodal hilar-mediastinal and lungs, III) an extended thoracic and extra-thoracic only nodal phenotype including inguinal-abdominal-supraclavicular stations, and IV) all the above plus systemic organs and tissues such as muscles-bones-spleen and skin. Conclusion: Though further studies are necessary to confirm findings as patterns of disease behavior; the proposed phenotypes may prove useful in the design of future studies with homogeneous cohorts facilitating in sarcoidosis patients a personalized medicine approach.
Cooperative Immune-Mediated Mechanisms of the HDAC Inhibitor Entinostat, an IL15 Superagonist, and a Cancer Vaccine Effectively Synergize as a Novel Cancer Therapy

Purpose: Immunotherapy has demonstrated clinical efficacy in subsets of patients with solid carcinomas. Multimodal therapies using agents that can affect different arms of the immune system and/or tumor microenvironment (TME) might increase clinical responses. Experimental Design: We demonstrate that entinostat, a class I histone deacetylase inhibitor, enhances the antitumor efficacy of the IL15 superagonist N-803 plus vaccine in 4T1 triple-negative breast and MC38-CEA colon murine carcinoma models. A comprehensive immune and gene-expression analysis was performed in the periphery and/or TME of MC38-CEA tumor–bearing mice. Results: Although N-803 plus vaccine induced peripheral CD8+ T-cell activation and cytokine production, there was no reduction in tumor burden and poor tumor infiltration of CD8+ T cells with minimal levels of granzyme B. For the first time, we demonstrate that the addition of entinostat to N-803 plus vaccine promoted significant tumor control, correlating with increased expression of genes associated with tumor inflammation, enhanced infiltration of activated CD8+ T cells with maximal granzyme B, T-cell responses to multiple tumor-associated antigens, increased serum IFNγ, reduction of regulatory T cells in the TME, and decreased expression of the checkpoint V-domain Ig suppressor of T-cell activation (VISTA) on multiple immune subsets. Conclusions: Collectively, these data demonstrate that the synergistic combination of entinostat, N-803, and vaccine elicits potent antitumor activity by generating a more inflamed TME. These findings thus form the rationale for the use of this combination of agents for patients harboring poorly or noninflamed solid carcinomas.
A Theoretically Grounded Exploration of Individual and Family Self-Management of Polycystic Ovary Syndrome in Adolescents

ABSTRACT Polycystic ovary syndrome (PCOS) is highly prevalent and increasingly diagnosed during adolescence. This study explored the context and processes of self-management among adolescents, and parents of adolescents, who have PCOS. Adolescents with PCOS (n = 7) and their parents (n = 8) participated in a series of focus groups. Deductive thematic analysis was guided by the Individual and Family Self-Management Theory (IFSMT), and the patterns that were identified aligned with the contexts and processes described therein. A secondary inductive approach was employed as a novel contextual pattern emerged: psychological health and well-being. Study findings suggest that adolescents and their families have a desire to engage in optimal self-management, and particularly effective strategies may consider a holistic, family intervention approach that addresses psychological health and well-being in addition to behavior change. Study findings are the first to reflect the unique needs of adolescents with PCOS and their families.
Influence of Ibuprofen on Bone Healing After Colles' Fracture: A Randomized Controlled Clinical Trial

Non‐steroidal anti‐inflammatory drugs (NSAIDs) may delay bone healing. [Therefore, it is important to establish whether NSAID preparations delay bone healing and what correlations, if any, exist between different bone studies—DEXA—scanning, bone markers, roentgenology controls, and histological examination of newly formed bone]. The purpose of this prospective controlled study was to investigate whether ibuprofen affects bone mineral density, turnover biomarkers, and histomorphometric characteristics of the callus after a Colles' fracture. This study was a single‐center, triple‐blinded, randomized clinical trial. Ninety‐five patients (80 females) with displaced Colles' fracture, median age 65 (range 40–85) years were included in the study and operated on by external fixation from June 2012 through to June 2015. Eighty‐nine patients received interventional medicine and 83 completed the 1‐year follow‐up. The 7‐day ibuprofen group received 600 mg of ibuprofen three times a day (N = 29), the 3‐day ibuprofen group received ibuprofen for 3 days (N = 30) and a placebo for the following 4 days, and finally, the placebo group received a placebo for 7 days (N = 30). The primary outcome was the difference in bone mineral density between the ultra‐distal region of the injured and non‐injured radius at 3 months after surgery. The histomorphometric outcomes included the assessment of callus tissue volume and surface fractions at 6 weeks postoperatively. The biomarkers Osteocalcin and CrossLaps were measured at baseline, 1 week, 2 weeks, 6 weeks, 3 months, and 1 year. We included the results of the dropped‐out patients in the intention to treat analysis. There was no difference between treatment groups in bone mineral density, histomorphometric estimations, and changes in bone biomarkers. These findings may offer an indication of ibuprofen as a bone‐safe analgesic treatment in an acute fracture‐phase. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:545–554, 2020