Miracle-dz/UniFAR-FTUs huggingface dataset:
Robust Methods for Real-Time Diabetic Foot Ulcer Detection and Localization on Mobile Devices

Current practice for diabetic foot ulcers (DFU) screening involves detection and localization by podiatrists. Existing automated solutions either focus on segmentation or classification. In this work, we design deep learning methods for real-time DFU localization. To produce a robust deep learning model, we collected an extensive database of 1775 images of DFU. Two medical experts produced the ground truths of this data set by outlining the region of interest of DFU with an annotator software. Using five-fold cross-validation, overall, faster R-CNN with InceptionV2 model using two-tier transfer learning achieved a mean average precision of 91.8%, the speed of 48 ms for inferencing a single image and with a model size of 57.2 MB. To demonstrate the robustness and practicality of our solution to real-time prediction, we evaluated the performance of the models on a NVIDIA Jetson TX2 and a smartphone app. This work demonstrates the capability of deep learning in real-time localization of DFU, which can be further improved with a more extensive data set.
Distribution of preoperative and postoperative astigmatism in a large population of patients undergoing cataract surgery in the UK

Purpose To assess the prevalence and severity of preoperative and postoperative astigmatism in patients with cataract in the UK. Setting Data from 8 UK National Health Service ophthalmology clinics using MediSoft electronic medical records (EMRs). Design Retrospective cohort study. Methods Eyes from patients aged ≥65 years undergoing cataract surgery were analysed. For all eyes, preoperative (corneal) astigmatism was evaluated using the most recent keratometry measure within 2 years prior to surgery. For eyes receiving standard monofocal intraocular lens (IOLs), postoperative refractive astigmatism was evaluated using the most recent refraction measure within 2–12 months postsurgery. A power vector analysis compared changes in the astigmatic 2-dimensional vector (J0, J45) before and after surgery, for the subgroup of eyes with both preoperative and postoperative astigmatism measurements. Visual acuity was also assessed preoperatively and postoperatively. Results Eligible eyes included in the analysis were 110 468. Of these, 78% (n=85 650) had preoperative (corneal) astigmatism ≥0.5 dioptres (D), 42% (n=46 003) ≥1.0 D, 21% (n=22 899) ≥1.5 D and 11% (n=11 651) ≥2.0 D. After surgery, the refraction cylinder was available for 39 744 (36%) eyes receiving standard monofocal IOLs, of which 90% (n=35 907) had postoperative astigmatism ≥0.5 D and 58% (n=22 886) ≥1.0 D. Visual acuity tended to worsen postoperatively with increased astigmatism (ρ=−0.44, P<0.01). Conclusions There is a significant burden of preoperative astigmatism in the UK cataract population. The available refraction data indicate that this burden is not reduced after surgery with implantation of standard monofocal IOLs. Measures should be taken to improve visual outcomes of patients with astigmatic cataract by simultaneously correcting astigmatism during cataract surgery.
Computational Modeling of Ultrasonic Subthalamic Nucleus Stimulation

Objective: To explore the potential of ultrasonic modulation of plateau-potential generating subthalamic nucleus neurons (STN), by modeling their interaction with continuous and pulsed ultrasonic waves. Methods: A computational model for ultrasonic stimulation of the STN is created by combining the Otsuka-model with the bilayer sonophore model. The neuronal response to continuous and pulsed ultrasonic waves is computed in parallel for a range of frequencies, duty cycles, pulse repetition frequencies, and intensities. Results: Ultrasonic intensity in continuous-wave stimulation determines the firing pattern of the STN. Three observed spiking modes in order of increasing intensity are low frequency spiking, high frequency spiking with significant spike-frequency and spike-amplitude adaptation, and a silenced mode. Continuous-wave stimulation has little capability to manipulate the saturated spiking rate in the high frequency spiking mode. In contrast, STN firing rates induced by pulsed ultrasound insonication will saturate to the pulse repetition frequency with short latencies, for sufficiently large intensity and repetition frequency. Conclusion: Computational results show that the activity of plateau-potential generating STN can be modulated by selection of the stimulus parameters. Low intensities result in repetitive firing, while higher intensities silence the STN. Pulsed ultrasonic stimulation results in a shorter saturation latency and is able to modulate spiking rates. Significance: Stimulation or suppresion of the STN is important in the treatment of Parkinson's disease, e.g., in deep brain stimulation. This explorative study on ultrasonic modulation of the STN, could be a step in the direction of minimally invasive alternatives to conventional deep brain stimulation.
CAMSAP3 maintains neuronal polarity through regulation of microtubule stability

Significance Each neuron forms a single axon and multiple dendrites, and this configuration is important for wiring the brain. How only a single axon extends from a neuron, however, remains unknown. This study demonstrates that CAMSAP3, a protein that binds the minus-end of microtubules, preferentially localizes along axons in hippocampal neurons. Remarkably, mutations of CAMSAP3 lead to production of multiple axons in these neurons. In attempts to uncover mechanisms underlying this abnormal axon extension, the authors found that CAMSAP3-anchored microtubules escape from acetylation, a process mediated by α-tubulin acetyltransferase-1, and depletion of this enzyme abolishes abnormal axon formation in CAMSAP3 mutants. These findings reveal that CAMSAP3 controls microtubule dynamics, preventing tubulin acetylation; this mechanism is required for single-axon formation. The molecular mechanisms that guide each neuron to become polarized, forming a single axon and multiple dendrites, remain unknown. Here we show that CAMSAP3 (calmodulin-regulated spectrin-associated protein 3), a protein that regulates the minus-end dynamics of microtubules, plays a key role in maintaining neuronal polarity. In mouse hippocampal neurons, CAMSAP3 was enriched in axons. Although axonal microtubules were generally acetylated, CAMSAP3 was preferentially localized along a less-acetylated fraction of the microtubules. CAMSAP3-mutated neurons often exhibited supernumerary axons, along with an increased number of neurites having nocodazole-resistant/acetylated microtubules compared with wild-type neurons. Analysis using cell lines showed that CAMSAP3 depletion promoted tubulin acetylation, and conversely, mild overexpression of CAMSAP3 inhibited it, suggesting that CAMSAP3 works to retain nonacetylated microtubules. In contrast, CAMSAP2, a protein related to CAMSAP3, was detected along all neurites, and its loss did not affect neuronal polarity, nor did it cause increased tubulin acetylation. Depletion of α-tubulin acetyltransferase-1 (αTAT1), the key enzyme for tubulin acetylation, abolished CAMSAP3 loss-dependent multiple-axon formation. These observations suggest that CAMSAP3 sustains a nonacetylated pool of microtubules in axons, interfering with the action of αTAT1, and this process is important to maintain neuronal polarity.
Pigs that recover from porcine reproduction and respiratory syndrome virus infection develop cytotoxic CD4+CD8+ and CD4+CD8- T-cells that kill virus infected cells

Porcine reproductive and respiratory syndrome virus (PRRSV) infection is difficult to control because the virus undergoes antigenic variation during infection and also modulates the protective host immune response. Although current vaccines do not provide full protection, they have provided insight into the mechanisms of protection. Live PRRSV vaccines induce partial protection before the appearance of neutralizing antibody, suggesting cell-mediated immunity or other mechanisms may be involved. Herein, we demonstrate recovery from infection is associated with development of cytotoxic T-lymphocytes (CTL) that can kill PRRSV-infected target cells. Initial experiments showed survival of PRRSV-infected monocyte derived macrophage (MDM) targets is reduced when overlaid with peripheral blood mononuclear cells (PBMC) from gilts that had recovered from PRRSV infection. Further studies with PBMC depleted of either CD4+ or CD8+ T-cells and positively selected subpopulations of CD4+ and CD8+ T-cells showed that both CD4+ and CD8+ T-cells were involved in killing. Examination of killing at different time points revealed killing was biphasic and mediated by CTL of different phenotypes. CD4+CD8+high were associated with killing target cells infected for 3–6 hours. CD4+CD8- CTL were associated with killing at 16–24 hours. Thus, all the anti-PRRSV CTL activity in pigs was attributed to two phenotypes of CD4+ cells which is different from the anti-viral CD4-CD8+ CTL phenotype found in most other animals. These findings will be useful for evaluating CTL responses induced by current and future vaccines, guiding to a novel direction for future vaccine development.
Cell wall integrity modulates Arabidopsis thaliana cell cycle gene expression in a cytokinin- and nitrate reductase-dependent manner

ABSTRACT During plant growth and defense, cell cycle activity needs to be coordinated with cell wall integrity. Little is known about how this coordination is achieved. Here, we investigated coordination in Arabidopsis thaliana seedlings by studying the impact of cell wall damage (CWD, caused by cellulose biosynthesis inhibition) on cytokinin homeostasis, cell cycle gene expression and cell shape in root tips. CWD inhibited cell cycle gene expression and increased transition zone cell width in an osmosensitive manner. These results were correlated with CWD-induced, osmosensitive changes in cytokinin homeostasis. Expression of CYTOKININ OXIDASE/DEHYDROGENASE 2 and 3 (CKX2, CKX3), which encode cytokinin-degrading enzymes, was induced by CWD and reduced by osmoticum treatment. In nitrate reductase1 nitrate reductase2 (nia1 nia2) seedlings, CKX2 and CKX3 transcript levels were not increased and cell cycle gene expression was not repressed by CWD. Moreover, established CWD-induced responses, such as jasmonic acid, salicylic acid and lignin production, were also absent, implying a central role of NIA1/2-mediated processes in regulation of CWD responses. These results suggest that CWD enhances cytokinin degradation rates through a NIA1/2-mediated process, leading to attenuation of cell cycle gene expression. Summary: A mechanism is identified in Arabidopsis thaliana that mediates cell cycle modification in response to plant cell wall damage through controlled changes in cytokinin levels.
Thermostable Xylanase Production by Geobacillus sp. Strain DUSELR13, and Its Application in Ethanol Production with Lignocellulosic Biomass

The aim of the current study was to optimize the production of xylanase, and its application for ethanol production using the lignocellulosic biomass. A highly thermostable crude xylanase was obtained from the Geobacillus sp. strain DUSELR13 isolated from the deep biosphere of Homestake gold mine, Lead, SD. Geobacillus sp. strain DUSELR13 produced 6 U/mL of the xylanase with the beechwood xylan. The xylanase production was improved following the optimization studies, with one factor at a time approach, from 6 U/mL to 19.8 U/mL with xylan. The statistical optimization with response surface methodology further increased the production to 31 U/mL. The characterization studies revealed that the crude xylanase complex had an optimum pH of 7.0, with a broad pH range of 5.0–9.0, and an optimum temperature of 75 °C. The ~45 kDa xylanase protein was highly thermostable with t1/2 of 48, 38, and 13 days at 50, 60, and 70 °C, respectively. The xylanase activity increased with the addition of Cu+2, Zn+2, K+, and Fe+2 at 1 mM concentration, and Ca+2, Zn+2, Mg+2, and Na+ at 10 mM concentration. The comparative analysis of the crude xylanase against its commercial counterpart Novozymes Cellic HTec and Dupont, Accellerase XY, showed that it performed better at higher temperature, hydrolyzing 65.4% of the beechwood at 75 °C. The DUSEL R13 showed the mettle to hydrolyze, and utilize the pretreated, and untreated lignocellulosic biomass: prairie cord grass (PCG), and corn stover (CS) as the substrate, and gave a maximum yield of 20.5 U/mL with the untreated PCG. When grown in co-culture with Geobacillus thermoglucosidasius, it produced 3.53 and 3.72 g/L ethanol, respectively with PCG, and CS. With these characteristics the xylanase under study could be an industrial success for the high temperature bioprocesses.
Recovering a Single Community With Side Information

We study the effect of the quality and quantity of side information on the recovery of a hidden community of size <inline-formula> <tex-math notation="LaTeX">$K=o(n)$ </tex-math></inline-formula> in a graph of size <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula>. Side information for each node in the graph is modeled by a random vector in which either the vector dimension or the LLR of each component with respect to node labels is independent of <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula>. These two models represent the variation in quality and quantity of side information. Under maximum likelihood detection, we calculate tight necessary and sufficient conditions for exact recovery of the labels. We demonstrate how side information needs to evolve with <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula> in terms of either its quantity, or quality, to improve the exact recovery threshold. A similar set of results are obtained for weak recovery. Under belief propagation, tight necessary and sufficient conditions for weak recovery are calculated when the LLRs are constant, and sufficient conditions when the LLRs vary with <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula>. Moreover, we design and analyze a local voting procedure using side information that can achieve exact recovery when applied after belief propagation.
Detection of regulatory T cell phenotypic markers and cytokines in patients with human papillomavirus infection

Infection with human papillomavirus (HPV) is the main cause of cervical cancer. Viral persistence is considered the main risk factor for neoplastic progression and evidence suggests that regulatory T cells (Treg) play an important role in the failure of viral elimination. The aim of this study was to detect phenotypic markers of Treg and cytokines interleukin (IL)‐10 and transforming growth factor (TGF)‐β, in the cervical microenvironment of HPV‐infected patients. One hundred and one samples of uterine cervix embedded in paraffin were analyzed. We used immunohistochemistry to examine the coexpression of the CD25/FOXP3 and CD4/TGF‐β markers, and the expression of GITR and IL‐10 in cells present in the cervical stroma. We detected a microenvironment composed of high proportions of CD25+FOXP3+, CD4+TGFβ+, IL‐10+, and GITR+ cells in samples with high viral loads and severe lesions of HPV‐infected patients. The abundance of these markers, indicative of the presence of Treg cells and immunosuppressive cytokines, was significantly associated with severe lesions and elevated viral loads in the examined samples. These results suggest that Treg cells may be involved in maintaining a microenvironment favorable for viral persistence and neoplastic progression. Our findings support those of previous studies that suggested that these markers could be used to predict HPV persistence and neoplastic progression, and as potential targets for immune response modulation.
Hyper-Objective Vortices

Almost all properties of vector fields, including magnitude, direction, <inline-formula><tex-math notation="LaTeX">$\lambda _2$</tex-math><alternatives><mml:math><mml:msub><mml:mi>λ</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:math><inline-graphic xlink:href="guenther-ieq1-2868760.gif"/></alternatives></inline-formula> and vorticity change under arbitrary movements of the observer. This is undesirable since measurements of physical properties should ideally not depend on the way the (virtual) measurement device moves. There are some properties that are invariant under certain types of reference frame transformations: Galilean invariance (invariance under equal-speed translation) and objectivity (invariance under any smooth rotation and translation of the reference frame). In this paper, we introduce even harder conditions than objectivity: we demand invariance under any smooth similarity transformation (rotation, translation and uniform scale) as well as invariance under any smooth affine transformation of the reference frame. We show that these new hyper-objective measures allow the extraction of vortices that change their volume or deform. Further, we present a generic approach that transforms almost any vortex measure into a hyper-objective one. We apply our methods to vortex extraction in 2D and 3D vector fields, and analyze the numerical robustness, extraction time and the minimization residuals for the Galilean invariant, objective, and the two new hyper-objective approaches.
Blood lysosphingolipids accumulation in patients with parkinson's disease with glucocerebrosidase 1 mutations

Introduction: Glucocerebrosidase 1 mutations, the most common genetic contributor to Parkinson's disease (PD), have been associated with decreased glucocerebrosidase enzymatic activity in PD patients with glucocerebrosidase 1 mutations (glucocerebrosidase 1–PD). However, it is unknown whether this decrease in enzymatic activity leads to lysosphingolipid accumulations.
The Association between US Adolescents’ Weight Status, Weight Perception, Weight Satisfaction, and Their Physical Activity and Dietary Behaviors

Background: It remain unclear that the association between weight status, weight perception, weight satisfaction and the clustering of physical activity (PA) and dietary behaviors in adolescents. Method: A cross-sectional analysis of National Health and Nutrition Examination Survey and the US Department of Agriculture’s Food Patterns Equivalents 2007–2014 data from adolescents aged 12–17 years (n = 2965) was conducted. Multivariable logistic regression models adjusted for demographic characteristics examined the association between weight status, weight perception, weight satisfaction, and the four created lifestyle groups (healthier behaviors, healthier diet only, physically active only, unhealthier behaviors). Results: Males with obesity were more likely to be in the healthier diet only group than males with a normal weight (OR = 1.90, 95% CI: 1.02, 3.52). Similar patterns were found in males who perceived themselves as being overweight or having obesity (OR = 2.09, 95% CI: 1.09, 3.99) and males with obesity who perceived their weight status accurately (OR = 2.33, 95% CI: 1.12, 4.88). Female respondents who were satisfied with their weight were 59% less likely to be in the healthier diet only group than healthier behaviors group compared with females who were weight dissatisfied (OR = 0.41, 95% CI: 0.23, 0.75). This pattern was not observed in males. Conclusions: Clustering PA and dietary behaviors were associated with weight status and weight perception for males but not females. Weight satisfaction was associated with clustered PA and dietary behaviors for females. These findings are important for obesity prevention policies and programs to better address adolescents’ obesity and reduce health disparities in this population.
Towards understanding aromatase inhibitory activity via QSAR modeling

Aromatase is a rate-limiting enzyme for estrogen biosynthesis that is overproduced in breast cancer tissue. To block the growth of breast tumors, aromatase inhibitors (AIs) are employed to bind and inhibit aromatase in order to lower the amount of estrogen produced in the body. Although a number of synthetic aromatase inhibitors have been released for clinical use in the treatment of hormone-receptor positive breast cancer, these inhibitors may lead to undesirable side effects (e.g. increased rash, diarrhea and vomiting; effects on the bone, brain and heart) and therefore, the search for novel AIs continues. Over the past decades, there has been an intense effort in employing medicinal chemistry and quantitative structure-activity relationship (QSAR) to shed light on the mechanistic basis of aromatase inhibition. To the best of our knowledge, this article constitutes the first comprehensive review of all QSAR studies of both steroidal and non-steroidal AIs that have been published in the field. Herein, we summarize the experimental setup of these studies as well as summarizing the key features that are pertinent for robust aromatase inhibition.
Optical and thermal simulations for the design of optodes for minimally invasive optogenetics stimulation or photomodulation of deep and large cortical areas in non-human primate brain

The use of optogenetics or photobiomodulation in non-human primate (NHP) requires the ability to noninvasively stimulate large and deep cortical brain tissues volumes. In this context, the optical and geometrical parameters of optodes are critical. Methods and general guidelines to optimize these parameters have to be defined. Objective. We propose the design of an optode for safe and efficient optical stimulation of a large volume of NHP cortex, down to 3–5 mm depths without inserting fibers into the cortex. Approach. Monte Carlo simulations of optical and thermal transport have been carried out using the Geant4 application for tomographic emission (GATE) platform. Parameters such as the fiber diameter, numerical aperture, number of fibers and their geometrical arrangement have been studied. Optimal hardware parameters are proposed to obtain homogeneous fluence above the fluence threshold for opsin activation without detrimental thermal effects. Main results. The simulations show that a large fiber diameter and a large numerical aperture are preferable since they allow limiting power concentration and hence the resulting thermal increases at the brain surface. To obtain a volume of 200–500 mm3 of brain tissues receiving a fluence above the opsin activation threshold for optogenetics or below a phototocixity threshold for photobiomodulation, a 4 fibers configuration is proposed. The optimal distance between the fibers was found to be 4 mm. A practical implementation of the optode has been performed and the corresponding fluence and thermal maps have been simulated. Significance. The present study defines a method to optimize the design of optode and the choice of stimulation parameters for optogenetics and more generally light delivery to deep and large volumes of tissues in NHP brain with a controlled irradiance dosimetry. The general guidelines are the use of silica fibers with a large numerical aperture and a large diameter. The combination of several fibers is required if large volumes need to be stimulated while avoiding thermal effects.