Miracle-dz/UniFAR-FTUs huggingface dataset:
Oscillatory recurrent gated neural integrator circuits (ORGaNICs), a unifying theoretical framework for neural dynamics

Significance Oscillatory recurrent gated neural integrator circuits (ORGaNICs) are a family of recurrent neural circuits that can simulate a wide range of neurobiological phenomena, various of which have each been explained by different models. This theoretical framework can be used to simulate neural activity with complex dynamics, including sequential and traveling waves of activity. When used to model cognitive processing in the brain, these circuits can both maintain and manipulate information during a working memory task. When used to model motor control, these circuits convert spatial patterns of premotor activity to temporal profiles of motor control activity. ORGaNICs offer a conceptual framework; rethinking cortical computation in these terms should have widespread implications, motivating a variety of experiments. Working memory is an example of a cognitive and neural process that is not static but evolves dynamically with changing sensory inputs; another example is motor preparation and execution. We introduce a theoretical framework for neural dynamics, based on oscillatory recurrent gated neural integrator circuits (ORGaNICs), and apply it to simulate key phenomena of working memory and motor control. The model circuits simulate neural activity with complex dynamics, including sequential activity and traveling waves of activity, that manipulate (as well as maintain) information during working memory. The same circuits convert spatial patterns of premotor activity to temporal profiles of motor control activity and manipulate (e.g., time warp) the dynamics. Derivative-like recurrent connectivity, in particular, serves to manipulate and update internal models, an essential feature of working memory and motor execution. In addition, these circuits incorporate recurrent normalization, to ensure stability over time and robustness with respect to perturbations of synaptic weights.
Quantitative Analysis of Major Metals in Agricultural Biochar Using Laser-Induced Breakdown Spectroscopy with an Adaboost Artificial Neural Network Algorithm

To promote the green development of agriculture by returning biochar to farmland, it is of great significance to simultaneously detect heavy and nutritional metals in agricultural biochar. This work aimed first to apply laser-induced breakdown spectroscopy (LIBS) for the determination of heavy (Pb, Cr) and nutritional (K, Na, Ca, Mg, Cu, and Zn) metals in agricultural biochar. Each batch of collected biochar was prepared to a standardized sample using the separating and milling method. Two types of univariate analysis model were developed using peak intensity and integration area of the sensitive emission lines, but the performance did not satisfy the requirements of practical application because of the poor correlations between the measured values and predicted values, as well as large relative standard deviation of the prediction (RSDP) values. An ensemble learning algorithm, adaboost backpropagation artificial neural network (BP-Adaboost), was then used to develop the multivariate analysis models, which had a more robust performance than traditional univariate analysis, partial least squares regression (PLSR), and backpropagation artificial neural network (BP-ANN). The optimized RSDP values for K, Ca, Mg, and Cu were less than 10%, while the RSDP values for Pb, Cr, Zn, and Na were in the range of 10–20%. Moreover, the pairwise t-test of its prediction set showed that there was no significant difference between the measurements of LIBS and ICP-MS. The promising results indicate that rapid and simultaneous detection of major heavy and nutritional metals in agricultural biochar can be achieved using LIBS and reasonable chemometric algorithms.
Gender affirmative HIV care framework: Decisions on feminizing hormone therapy (FHT) and antiretroviral therapy (ART) among transgender women

Background Integration of feminizing hormone therapy (FHT) and antiretroviral therapy (ART) is critical in providing gender-affirming HIV care for transgender (trans) women living with HIV. However, interpersonal communications with HIV providers who are not competent with FHT may complicate this integration. Methods We conducted semi-structured interviews with trans women (n = 9) who self-reported as HIV-positive and their HIV providers (n = 15) from community-based venues (e.g., clinics) in Manila, Philippines. Results We identified five key themes from our qualitative data: (1) provider’s concerns; (2) patient’s goals; (3) affirmative vs. non-affirmative provider rhetoric; (4) alignment vs. misalignment of provider rhetoric to patient goals; and (5) FHT and ART-related decisions. Based on these themes, we describe a gender-affirmative HIV care framework to understand FHT-ART decisions among trans women living with HIV. Based on our data, this framework shows that provider-patient communications regarding ART and FHT consists primarily of provider concerns and patient goals regarding FHT. These communications can take on a gender-affirmative or non-affirmative style of rhetoric that either aligns or misaligns with patient goals and may lead to differences in FHT and ART-related decisions among trans women living with HIV. Conclusion There exist mixed regimens and beliefs about taking FHT and ART among this sample of trans women. While trans participants’ main source of health information is their HIV provider, providers are likely to communicate non-affirmative rhetoric that negatively impacts trans women’s decision to take FHT and ART. Research is needed to elucidate co-prescriptions of gender-affirmative services with HIV care among this group in the Philippines.
Advances in Understanding the Relationship between Sleep and Attention Deficit-Hyperactivity Disorder (ADHD)

Starting from the consolidated relationship between sleep and cognition, we reviewed the available literature on the association between Attention Deficit-Hyperactivity Disorder (ADHD) and sleep. This review analyzes the macrostructural and microstructural sleep features, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria (PRISMA). We included the polysomnographic studies published in the last 15 years. The results of macrostructural parameters are mixed. Almost half of the 18 selected investigations did not find differences between sleep architecture of children with ADHD and controls. Five studies observed that children with ADHD show a longer Rapid Eye Movement (REM) sleep duration than controls. Eight studies included microstructural measures. Remarkable alterations in sleep microstructure of ADHD are related to slow wave activity (SWA) and theta oscillations, respectively, during Non-REM (NREM) and REM sleep. Specifically, some studies found higher SWA in the ADHD group than controls. Similarly, higher theta activity appears to be detrimental for memory performance and inhibitory control in ADHD. These patterns could be interpreted as a maturational delay in ADHD. Also, the increased amount of these activities would be consistent with the hypothesis that the poor sleep could imply a chronic sleep deprivation in children with ADHD, which in turn could affect their cognitive functioning.
Cerium Oxide Nanoparticles Absorption through Intact and Damaged Human Skin

Cerium oxide (CeO2) nanoparticles (NPs) are used in polishing products and absorbents, as promoters in wound healing, and as organopesticide decontaminants. While systemic bioaccumulation and organ toxicity has been described after inhalation, data on CeO2 NPs’ transdermal permeation are lacking. Our study was an in vitro investigation of the permeation of 17-nm CeO2 NPs dispersed in synthetic sweat (1 g L−1) using excised human skin on Franz cells. Experiments were performed using intact and needle-abraded skin, separately. The average amount of Ce into intact and damaged skin samples was 3.64 ± 0.15 and 7.07 ± 0.78 µg cm−2, respectively (mean ± SD, p = 0.04). Ce concentration in the receiving solution was 2.0 ± 0.4 and 3.3 ± 0.7 ng cm−2 after 24 h (p = 0.008). The Ce content was higher in dermal layers of damaged skin compared to intact skin (2.93 ± 0.71 µg cm−2 and 0.39 ± 0.16 µg cm−2, respectively; p = 0.004). Our data showed a very low dermal absorption and transdermal permeation of cerium, providing a first indication of Ce skin uptake due to contact with CeO2.
Mimicking Sub-Structures Self-Organization in Microtubules

Microtubules (MTs) are highly dynamic polymers distributed in the cytoplasm of a biological cell. Alpha and beta globular proteins constituting the heterodimer building blocks combine to form these tubules through polymerization, controlled by the concentration of Guanosine-triphosphate (GTPs) and other Microtubule Associated Proteins (MAPs). MTs play a crucial role in many intracellular processes, predominantly in mitosis, organelle transport and cell locomotion. Current research in this area is focused on understanding the exclusive behaviors of self-organization and their association with different MAPs through organized laboratory experiments. However, the intriguing intelligence behind these tiny machines resulting in complex self-organizing structures is mostly unexplored. In this study, we propose a novel swarm engineering framework in modeling rules for these systems, by combining the principles of design with swarm intelligence. The proposed framework was simulated on a game engine and these simulations demonstrated self-organization of rings and protofilaments in MTs. Analytics from these simulations assisted in understanding the influence of GTPs on protofilament formation. Also, results showed that the population density of GTPs rather than their bonding probabilities played a crucial role in polymerization in forming microtubule substructures.
AMPK Activation Promotes Tight Junction Assembly in Intestinal Epithelial Caco-2 Cells

The AMP-activated protein kinase (AMPK) is principally known as a major regulator of cellular energy status, but it has been recently shown to play a key structural role in cell-cell junctions. The aim of this study was to evaluate the impact of AMPK activation on the reassembly of tight junctions in intestinal epithelial Caco-2 cells. We generated Caco-2 cells invalidated for AMPK α1/α2 (AMPK dKO) by CRISPR/Cas9 technology and evaluated the effect of the direct AMPK activator 991 on the reassembly of tight junctions following a calcium switch assay. We analyzed the integrity of the epithelial barrier by measuring the trans-epithelial electrical resistance (TEER), the paracellular permeability, and quantification of zonula occludens 1 (ZO-1) deposit at plasma membrane by immunofluorescence. Here, we demonstrated that AMPK deletion induced a delay in tight junction reassembly and relocalization at the plasma membrane during calcium switch, leading to impairments in the establishment of TEER and paracellular permeability. We also showed that 991-induced AMPK activation accelerated the reassembly and reorganization of tight junctions, improved the development of TEER and paracellular permeability after calcium switch. Thus, our results show that AMPK activation ensures a better recovery of epithelial barrier function following injury.
Efficient Parameter Estimation for Sparse SAR Imaging Based on Complex Image and Azimuth-Range Decouple

Sparse signal processing theory has been applied to synthetic aperture radar (SAR) imaging. In compressive sensing (CS), the sparsity is usually considered as a known parameter. However, it is unknown practically. For many functions of CS, we need to know this parameter. Therefore, the estimation of sparsity is crucial for sparse SAR imaging. The sparsity is determined by the size of regularization parameter. Several methods have been presented for automatically estimating the regularization parameter, and have been applied to sparse SAR imaging. However, these methods are deduced based on an observation matrix, which will entail huge computational and memory costs. In this paper, to enhance the computational efficiency, an efficient adaptive parameter estimation method for sparse SAR imaging is proposed. The complex image-based sparse SAR imaging method only considers the threshold operation of the complex image, which can reduce the computational costs significantly. By utilizing this feature, the parameter is pre-estimated based on a complex image. In order to estimate the sparsity accurately, adaptive parameter estimation is then processed in the raw data domain, combining with the pre-estimated parameter and azimuth-range decouple operators. The proposed method can reduce the computational complexity from a quadratic square order to a linear logarithm order, which can be used in the large-scale scene. Simulated and Gaofen-3 SAR data processing results demonstrate the validity of the proposed method.
Patients report inferior quality of care for knee osteoarthritis prior to assessment for knee replacement surgery – a cross-sectional study of 517 patients in Denmark

Background and purpose — Clinical care pathways for knee osteoarthritis (OA) are not always in line with clinical guidelines. We investigated (1) the patient-perceived quality of OA management, (2) which physiotherapist-delivered treatments patients with knee OA have attempted, and (3) patients’ expected subsequent treatment, at the time of referral to an orthopedic surgeon. Patients and methods — This cross-sectional study included all patients with scheduled first-time appointments for knee OA at an orthopedic outpatient clinic from April 2017 to February 2018. Postal questionnaires included the 16-item OsteoArthritis Quality Indicator (OA-QI) questionnaire and questions about physiotherapist-delivered treatment for knee OA. Results — 517 of 627 (82%) eligible patients responded. Responders’ (63% female) mean age was 67 years. The mean pass rate for the 16 independent quality indicators was 32% (8–74%). Sub-grouped into 4 categories, pass rates for independent quality indicators ranged from 16–52% regarding information, 9–50% regarding pain and functional assessment, 8–35% regarding referrals, and 16–74% regarding pharmacological treatment. While half of responders felt informed of physical activity benefits, only one-third had consulted a physiotherapist during the past year. Commonest physiotherapist-delivered treatments were exercise therapy for 22% and participation in the Good Life with osteoArthritis in Denmark (GLA:D) program for12% of responding patients. 65% expected surgery as subsequent treatment. Interpretation — Patients with knee OA are undertreated in primary care in Denmark; however, our findings may only reflect healthcare settings that are comparably organized. Our results call for better structure and uniform pathways for primary care knee OA treatment before referral to an orthopedic surgeon.
Serotonin 2C receptors in the basolateral amygdala mediate the anxiogenic effect caused by serotonergic activation of the dorsal raphe dorsomedial subnucleus

Background: Stimulation of serotonergic neurons within the dorsal raphe dorsomedial subnucleus facilitates inhibitory avoidance acquisition in the elevated T-maze. It has been hypothesized that such anxiogenic effect is due to serotonin release in the basolateral nucleus of the amygdala, where facilitation of serotonin 2C receptor-mediated neurotransmission increases anxiety. Besides the dorsal raphe dorsomedial subnucleus, the dorsal raphe caudal subnucleus is recruited by anxiogenic stimulus/situations. However, the behavioral consequences of pharmacological manipulation of this subnucleus are still unknown. Aims: Investigate whether blockade of serotonin 2C receptors in the basolateral nucleus of the amygdala counteracts the anxiogenic effect caused by the stimulation of dorsal raphe dorsomedial subnucleus serotonergic neurons. Evaluate the effects caused by the excitatory amino acid kainic acid or serotonin 1A receptor-modulating drugs in the dorsal raphe caudal subnucleus. Methods: Male Wistar rats were tested in the elevated T-maze and light-dark transition tests after intra-basolateral nucleus of the amygdala injection of the serotonin 2C receptor antagonist SB-242084 (6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride) followed by intra-dorsal raphe dorsomedial subnucleus administration of the serotonin 1A receptor antagonist WAY-100635 (N-[2-[4-2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinil-cyclohexanecarboxamide maleate). In the dorsal raphe caudal subnucleus, animals were injected with kainic acid, WAY-100635 or the serotonin 1A receptor agonist 8-OH-DPAT ((±)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide) and tested in the elevated T-maze. Results: SB-242084 in the basolateral nucleus of the amygdala blocked the anxiogenic effect caused by the injection of WAY-100635 in the dorsal raphe dorsomedial subnucleus. Kainic acid in the dorsal raphe caudal subnucleus increased anxiety, but also impaired escape expression in the elevated T-maze. Neither WAY-100635 nor 8-OH-DPAT in the dorsal raphe caudal subnucleus affected rat’s behavior in the elevated T-maze. Conclusion: Serotonin 2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect caused by the stimulation of serotonergic neurons in the dorsal raphe dorsomedial subnucleus. The dorsal raphe caudal subnucleus regulates anxiety- and panic-like behaviors, presumably by a serotonin 1A receptor-independent mechanism.
Creatine is Neuroprotective to Retinal Neurons In Vitro But Not In Vivo.

Purpose To investigate the neuroprotective properties of creatine in the retina using in vitro and in vivo models of injury. Methods Two different rat retinal culture systems (one containing retinal ganglion cells [RGC] and one not) were subjected to either metabolic stress, via treatments with the mitochondrial complex IV inhibitor sodium azide, or excitotoxic stress, via treatment with N-methyl-D-aspartate for 24 hours, in the presence or absence of creatine (0.5, 1.0, and 5.0 mM). Neuronal survival was assessed by immunolabeling for cell-specific antigens. Putative mechanisms of creatine action were investigated in vitro. Expression of creatine kinase (CK) isoenzymes in the rat retina was examined using Western blotting and immunohistochemistry. The effect of oral creatine supplementation (2%, wt/wt) on retinal and blood creatine levels was determined as well as RGC survival in rats treated with N-methyl-D-aspartate (NMDA; 10 nmol) or high IOP-induced ischemia reperfusion. Results Creatine significantly prevented neuronal death induced by sodium azide and NMDA in both culture systems. Creatine administration did not alter cellular adenosine triphosphate (ATP). Inhibition of CK blocked the protective effect of creatine. Retinal neurons, including RGCs, expressed predominantly mitochondrial CK isoforms, while glial cells expressed exclusively cytoplasmic CKs. In vivo, NMDA and ischemia reperfusion caused substantial loss of RGCs. Creatine supplementation led to elevated blood and retinal levels of this compound but did not significantly augment RGC survival in either model. Conclusions Creatine increased neuronal survival in retinal cultures; however, no significant protection of RGCs was evident in vivo, despite elevated levels of this compound being present in the retina after oral supplementation.
Extensive left atrial ablation was associated with exacerbation of left atrial stiffness and dyspnea

The left atrium (LA), including the pulmonary vein antrum, is the main target of catheter ablation for atrial fibrillation (AF). However, there is a lack of data on the effect of extensive LA ablation on LA stiffness. This study sought to investigate the impact of extensive LA ablation on LA stiffness and dyspnea after the restoration of sinus rhythm.
Hearing loss mutations alter the functional properties of human P2X2 receptor channels through distinct mechanisms

Significance In the cochlea, extracellular ATP-activated P2X2 receptor channels play important roles in adaptation to elevated sound, and several hP2X2 mutations cause inherited progressive sensorineural hearing loss. We investigated the functional properties of 3 mutants (V60L, D273Y, and G353R) and show that only the D273Y mutant results in nonfunctional channels. The V60L mutant exhibits constitutive activation and uncoupling between ATP binding and pore opening, while the G353R mutant exhibits altered sensitivity to ATP, inward rectification, and ion selectivity. Our results demonstrate that mutations in P2X2 receptors can cause hearing loss without completely disrupting channel function, highlighting the importance of these channels for protecting hearing. Activation of P2X2 receptor channels by extracellular ATP is thought to play important roles in cochlear adaptation to elevated sound levels and protection from overstimulation. Each subunit of a trimeric P2X2 receptor is composed of intracellular N and C termini, a large extracellular domain containing the ATP binding site and 2 transmembrane helices (TM1 and TM2) that form a cation permeable pore. Whole-exome sequencing and linkage analysis have identified 3 hP2X2 receptor mutations (V60L, D273Y, and G353R) that cause dominantly inherited progressive sensorineural hearing loss (DFNA41). Available structures of related P2X receptors suggest that these 3 mutations localize to TM1 (V60L), TM2 (G353R), or the β-sheet linking the TMs to the extracellular ATP binding sites (D273Y). Previous studies have concluded that the V60L and G353R mutants are nonfunctional, whereas the D273Y mutant has yet to be studied. Here, we demonstrate that both V60L and G353R mutations do form functional channels, whereas the D273Y mutation prevents the expression of functional channels on the cell membrane. Our results show that the V60L mutant forms constitutively active channels that are insensitive to ATP or the antagonist suramin, suggesting uncoupling of the pore and the ligand binding domains. In contrast, the G353R mutant can be activated by ATP but exhibits alterations in sensitivity to ATP, inward rectification, and ion selectivity. Collectively, our results demonstrate that the loss of functional P2X2 receptors or distinct alterations of its functional properties lead to noise-induced hearing loss, highlighting the importance of these channels in preserving hearing.
Personalized treatment selection using data from crossover designs with carry‐over effects

In this work, we propose a semiparametric method for estimating the optimal treatment for a given patient based on individual covariate information for that patient when data from a crossover design are available. Here, we assume there are carry‐over effects for patients switching from one treatment to another. For the K treatment (K ≥ 2) scenario, we show that nonparametric estimation of carry‐over effects can have the undesirable property that comparison of treatment means can only be done using independent outcome measurements from different groups of patients rather than using available joint measurements for each patient. To overcome this barrier, we compare probabilities of outcome variable of each treatment dominating outcome variables for all other treatments conditional on patient‐specific scores constructed from patient covariates. We suggest single‐index models as appropriate models connecting outcome variables to covariates and our empirical investigations show that frequencies of correct treatment assignments are highly accurate. The proposed method is also rather robust against departures from a single‐index model structure. We also conduct a real data analysis to show the applicability of the proposed procedure.