Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple Modulation of Acid-Sensing Ion Channel 1a by the Alkaloid Daurisoline

Acid-sensing ion channels (ASICs) are proton-gated sodium-selective channels that are expressed in the peripheral and central nervous systems. ASIC1a is one of the most intensively studied isoforms due to its importance and wide representation in organisms, but it is still largely unexplored as a target for therapy. In this study, we demonstrated response of the ASIC1a to acidification in the presence of the daurisoline (DAU) ligand. DAU alone did not activate the channel, but in combination with protons, it produced the second peak component of the ASIC1a current. This second peak differs from the sustained component (which is induced by RF-amide peptides), as the second (DAU-induced) peak is completely desensitized, with the same kinetics as the main peak. The co-application of DAU and mambalgin-2 indicated that their binding sites do not overlap. Additionally, we found an asymmetry in the pH activation curve of the channel, which was well-described by a mathematical model based on the multiplied probabilities of protons binding with a pool of high-cooperative sites and a single proton binding with a non-cooperative site. In this model, DAU targeted the pool of high-cooperative sites and, when applied with protons, acted as an inhibitor of ASIC1a activation. Moreover, DAU’s occupation of the same binding site most probably reverses the channel from steady-state desensitization in the pH 6.9–7.3 range. DAU features disclose new opportunities in studies of ASIC structure and function.
Cobalt-Containing Nanoporous Nitrogen-Doped Carbon Nanocuboids from Zeolite Imidazole Frameworks for Supercapacitors

Pyrolyzing metal–organic frameworks (MOFs) typically yield composites consisting of metal/metal oxide nanoparticles finely dispersed on carbon matrices. The blend of pseudocapacitive metal oxides and conductive metals, as well as highly porous carbon networks, offer unique opportunities to obtain supercapacitor electrodes with mutually high capacitances and excellent rate capabilities. Herein, we demonstrate nitrogen-doped carbon nanocuboid arrays grown on carbon fibers and incorporating cobalt metal and cobalt metal oxides. This composite was synthesized via pyrolysis of a chemical bath deposited MOF, cobalt-containing zeolite imidazole framework (Co–ZIF). The active materials for charge storage are the cobalt oxide and nitrogen-doped carbon. Additionally, the Co metal and the nanoporous carbon network facilitated electron transport and the rich nanopores in each nanocuboid shortened ion diffusion distance. Benefited from these merits, our Co–ZIF-derived electrode delivered an areal capacitance of 1177 mF cm−2 and excellent cycling stability of ~94% capacitance retained after 20,000 continuous charge–discharge cycles. An asymmetric supercapacitor prototype having the Co–ZIF-derived hybrid material (positive electrode) and activated carbon (negative electrode) achieved a maximal volumetric energy density of 1.32 mWh cm−3 and the highest volumetric power density of 376 mW cm−3. This work highlights the promise of metal–metal oxide–carbon nanostructured composites as electrodes in electrochemical energy storage devices.
Cross-cultural adaptation and psychometric properties of the European Portuguese version of the Global Perceived Effect Scale in patients with chronic low back pain

Abstract Purpose To cross-culturally adapt the Global Perceived Effect Scale (GPES) into Portuguese and investigate its psychometric properties in patients with chronic low back pain. Methods Cross-cultural adaptation was carried out according to published guidelines. Along with measures for pain and disability, GPES was administered at baseline, 48-h later and post-intervention. To estimate test-retest reliability, the intraclass correlation coefficient was used. The validity was examined through the correlation between the GPES and the Patient Global Improvement Change Scale and the contribution of baseline status to GPES scores. Responsiveness was assessed by analyzing hypotheses regarding areas under the curve and correlations with changes in other measures. Results The test-retest reliability, the convergent validity and the contribution of the baseline status to GPES scores were demonstrated. The EPES correlated strongly with global perception of change (r = 0.677), and moderately with pain and disability changes (r = 0.457 and r = 0.452, respectively). Areas under the curve values of 0.71(95% CI = 0.607–0.825) and 0.83 (95% CI = 0.749–922) were found. Conclusion The GPES demonstrated adequate psychometric properties. This study’s findings supported its use in clinical and research studies with patients with chronic low back pain. IMPLICATIONS FOR REHABILITATION The European Portuguese version of the Global Perceived Effect Scale demonstrated adequate reliability, validity and responsiveness. This instrument is suitable to evaluate meaningful changes in patients with chronic low back pain. The contribution of baseline status to GPES scores was confirmed by specific and recommended methods. The use of the GPES as external criterion of change in clinimetric studies was supported. The minimum important change was 2.5 points out of 11 of the GPES. Only improvements above this point should be considered as relevant to patients with chronic low back pain undergoing physiotherapy.
NOP receptor antagonists decrease alcohol drinking in the dark in C57BL/6J mice.

BACKGROUND The nociceptin/orphanin FQ opioid peptide (NOP) receptor and its endogenous ligand N/OFQ have been implicated in the regulation of drug and alcohol use disorders. In particular, evidence demonstrated that NOP receptor activation blocks reinforcing and motivating effects of alcohol across a range of behavioral measures, including alcohol intake, conditioned place preference and vulnerability to relapse. METHODS Here, we show the effects of pharmacological activation and inhibition of NOP receptors on binge-like alcohol consumption, as measured by the "drinking in the dark" (DID) model in C57BL/6J mice. RESULTS We found that two potent and selective NOP agonists AT-202 (0, 0.3, 1, 3 mg/kg) and AT-312 (0, 0.3, 1 mg/kg) did not affect binge alcohol drinking at doses that do not affect locomotor activity. AT-202 also failed to alter DID behavior when administered to mice previously exposed to chronic alcohol treatment with an alcohol-containing liquid diet. Conversely, treatment with either the high affinity NOP receptor antagonist SB-612111 (0, 3, 10, 30 mg/kg) or the selective antagonist LY2817412 (0, 3, 10, 30 mg/kg) decreased binge drinking. SB-612111 was effective at all doses examined, LY2817412 was effective at 30 mg/kg. Consistently, NOP receptor knockout mice consumed less alcohol compared to wild type. SB-612111 reduced DID and increased sucrose consumption at doses that do not appear to affect locomotor activity. However, the high dose of SB-612111 (30 mg/kg) reduced alcohol intake but failed to inhibit preference in a two-bottle choice DID model that can assess moderate alcohol intake. CONCLUSIONS The present results suggest that NOP receptor inhibition rather than activation may represent a valuable approach for treatment of alcohol use disorders characterized by excessive alcohol consumption such as binge drinking. This article is protected by copyright. All rights reserved.
Clinical pathologies of bone fracture modelled in zebrafish

ABSTRACT Reduced bone quality or mineral density predict susceptibility to fracture and also attenuate subsequent repair. Bone regrowth is also compromised by bacterial infection, which exacerbates fracture site inflammation. Because of the cellular complexity of fracture repair, as well as genetic and environmental influences, there is a need for models that permit visualisation of the fracture repair process under clinically relevant conditions. To characterise the process of fracture repair in zebrafish, we employed a crush fracture of fin rays, coupled with histological and transgenic labelling of cellular responses; the results demonstrate a strong similarity to the phased response in humans. We applied our analysis to a zebrafish model of osteogenesis imperfecta (OI), which shows reduced bone quality, spontaneous fractures and propensity for non-unions. We found deficiencies in the formation of a bone callus during fracture repair in our OI model and showed that clinically employed antiresorptive bisphosphonates can reduce spontaneous fractures in OI fish and also measurably reduce fracture callus remodelling in wild-type fish. The csf1ra mutant, which has reduced osteoclast numbers, also showed reduced callus remodelling. Exposure to excessive bisphosphonate, however, disrupted callus repair. Intriguingly, neutrophils initially colonised the fracture site, but were later completely excluded. However, when fractures were infected with Staphylococcus aureus, neutrophils were retained and compromised repair. This work elevates the zebrafish bone fracture model and indicates its utility in assessing conditions of relevance to an orthopaedic setting with medium throughput. This article has an associated First Person interview with the first author of the paper. Summary: The effect of osteogenesis imperfecta, bisphosphonate treatment and bacterial infection on phases of bone fracture repair are determined using a zebrafish fracture model.
Deep tumor penetration of drug-loaded nanoparticles by click reaction-assisted immune cell targeting strategy.

Nanoparticles have been extensively used to deliver therapeutic drugs to tumor tissues through extravasation from a leaky vessel via enhanced permeation and retention effect (EPR, passive targeting) or targeted interaction of tumor-specific ligands (active targeting). However, the therapeutic efficacy of drug-loaded nanoparticles is hampered by heterogeneous distribution owing to limited penetration in tumor tissue. Inspired by the fact that cancer cells can recruit inflammatory immune cells to support their survival, we developed a click reaction-assisted immune cell targeting (CRAIT) strategy to deliver drug-loaded nanoparticles deep into avascular regions of the tumor. Immune cell-targeting CD11b antibodies are modified with trans-cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 hr results in targeted conjugation of the nanoparticles onto CD11b+ myeloid cells, which serve as active vectors into tumor interiors. We show that the CRAIT strategy allows deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model. The CRAIT strategy does not require ex vivo manipulation of cells and can be applied to various types of cells and nanovehicles.
Mitochondrial translocation of cyclin C stimulates intrinsic apoptosis through Bax recruitment

Intrinsic apoptosis requires mitochondrial outer membrane disruption triggered by recruitment, activation, and oligomerization of the Bcl‐2 homology protein Bax. Following oxidative stress, we demonstrated that the transcriptional regulator cyclin C is released into the cytosol where it directs mitochondrial fragmentation and efficient apoptotic induction. This study reveals that cytoplasmic cyclin C is required for both normal Bax activation and its efficient mitochondrial localization. This activity appears direct as cyclin C co‐immunoprecipitates with active Bax in stressed cells and binds recombinant Bax in vitro. In addition, stable cyclin C–Bax association requires the fission complex. Pharmacologically stimulating cyclin C nuclear release is sufficient for Bax association and their mitochondrial localization in the absence of any stress signals. However, these cells do not undergo cell death as Bax fails to oligomerize. These data support a model that cyclin C association defines an initial step in Bax mitochondrial recruitment and provides a physical connection between the fission and apoptotic factors. This strategy allows the cell to discriminate stress‐induced fission able to recruit Bax from other types of mitochondrial divisions.
Blood Pressure Estimation from Photoplethysmogram Using a Spectro-Temporal Deep Neural Network

Blood pressure (BP) is a direct indicator of hypertension, a dangerous and potentially deadly condition. Regular monitoring of BP is thus important, but many people have aversion towards cuff-based devices, and their limitation is that they can only be used at rest. Using just a photoplethysmogram (PPG) to estimate BP is a potential solution investigated in our study. We analyzed the MIMIC III database for high-quality PPG and arterial BP waveforms, resulting in over 700 h of signals after preprocessing, belonging to 510 subjects. We then used the PPG alongside its first and second derivative as inputs into a novel spectro-temporal deep neural network with residual connections. We have shown in a leave-one-subject-out experiment that the network is able to model the dependency between PPG and BP, achieving mean absolute errors of 9.43 for systolic and 6.88 for diastolic BP. Additionally we have shown that personalization of models is important and substantially improves the results, while deriving a good general predictive model is difficult. We have made crucial parts of our study, especially the list of used subjects and our neural network code, publicly available, in an effort to provide a solid baseline and simplify potential comparison between future studies on an explicit MIMIC III subset.
Normal Versus Abnormal ECG Classification by the Aid of Deep Learning

With the development of telemedicine systems, collected ECG records are accumulated on a large scale. Aiming to lessen domain experts ’ workload, we propose a new method based on lead convolutional neural network (LCNN) and rule inference for classification of normal and abnormal ECG records with short duration. First, two different LCNN models are obtained through different filtering methods and different training methods, and then the multipoint-prediction technology and the Bayesian fusion method are successively applied to them. As beneficial complements, four newly developed disease rules are also involved. Finally, we utilize the bias-average method to output the predictive value. On the Chinese Cardiovascular Disease Database with more than 150,000 ECG records, our proposed method yields an accuracy of 86.22% and 0.9322 AUC (Area under ROC curve), comparable to the state-of-the-art results for this subject.
Unhealthy Lifestyle Associated with Higher Intake of Sugar-Sweetened Beverages among Malaysian School-Aged Adolescents

High consumption of sugar-sweetened beverages (SSBs) among adolescents has turned into a global concern due to its negative impact on health. This cross-sectional study determined the amount of SSB consumption among adolescents and its associated factors. A total of 421 adolescents aged 13.3 ± 1.3 years (41.8% males, 58.2% females) completed a self-administered questionnaire on sociodemographic characteristics, physical activity, screen-viewing behavior, sleep quality, frequency of eating at fast food restaurants, home food availability, peer social pressure, parenting practice, and SSB consumption. Weight and height were measured. Results showed that the mean daily consumption of SSBs among adolescents was 1038.15 ± 725.55 mL. The most commonly consumed SSB was malted drink, while the least commonly consumed SSB was instant coffee. The multiple linear regression results revealed that younger age (β = −0.204, p < 0.001), higher physical activity (β = 0.125, p = 0.022), higher screen time (β = 0.147, p = 0.007), poorer sleep quality (β = 0.228, p < 0.001), and unhealthy home food availability (β = 0.118, p = 0.032) were associated with a higher SSB intake. Therefore, promoting a healthy lifestyle may help to reduce the excessive consumption of SSBs among adolescents.
The effect of action observation and motor imagery combinations on upper limb kinematics and EMG during dart‐throwing

Recent research has begun to employ interventions that combine action observation and motor imagery (AOMI) with positive results. However, little is known about the underpinning facilitative effect on performance. Participants (n = 50) were randomly allocated to one of five training groups: action observation (AO), motor imagery (MI), simultaneous action observation and motor imagery (S‐AOMI), alternate action observation and motor imagery (A‐AOMI), and control. The task involved dart‐throwing at a concentric circle dartboard at pre‐ and post‐test. Interventions were conducted 3 times per week for 6 weeks. Data were collected from performance outcomes and mean muscle activation of the upper and forearm muscles. Angular velocity and peak angular velocity measurements of the elbow were also collected from the throwing arm. Results showed performance of the A‐AOMI group improved to a significantly greater degree than the AO (P = .04), MI (P = .04), and control group (P = .02), and the S‐AOMI group improved to a greater degree than the control group (P = .02). Mean muscle activation of the triceps brachii significantly reduced in the S‐AOMI and A‐AOMI (P < .01) groups, and participants in the AO (P = .04), A‐AOMI, and S‐AOMI (P < .01) groups significantly reduced activation in the bicep brachii from pre‐ to post‐test. Peak angular velocity significantly decreased from pre‐ to post‐test in both A‐AOMI and S‐AOMI (P < .01) groups. The results reaffirm the benefits of AOMI for facilitating skill learning and provide an insight how these interventions produce favorable changes in EMG and movement kinematics.
Treatment Attitudes and Adherence Among Patients with Bipolar Disorder: A Systematic Review of Quantitative and Qualitative Studies.

BACKGROUND Systematic reviews about treatment attitudes of patients influencing adherence in bipolar disorder (BD) are rare. METHODS A systematic review was conducted according to the PRISMA guidelines and principles of thematic synthesis. Selectively identified quantitative and qualitative studies were used to examine the attitude-adherence relationship in BD, the types and correlates of treatment attitudes, and the impact of psychosocial interventions on attitudes. RESULTS The final list of 163 articles included 114 observational reports (incorporating 21 psychosocial intervention trials), 45 qualitative/descriptive studies, and 4 patient surveys. A positive association between treatment attitudes and adherence was found in most quantitative and qualitative studies, though the strength of the relationship was unclear. Thematic analysis of qualitative studies suggested that patient attitudes influencing adherence were based on perceived advantages and disadvantages of treatment. The principal correlates of patients' attitudes were family attitudes, the clinician-patient alliance, social support, and patients' knowledge of BD. Though negative attitudes such as denial, concerns about adverse treatment consequences, and stigmatizing effects of treatment were common, many patients believed treatment to be beneficial and necessary. The limited data on the effect of psychosocial interventions indicated that treatments selectively targeting attitudes enhanced adherence. LIMITATIONS The studies were heterogeneous in design; the quality was uneven (fair to poor); and the risk of bias moderate to high. CONCLUSIONS Despite these flaws, awareness of the existing evidence on the attitude-adherence association and other aspects of treatment attitudes in BD can help in efforts to address nonadherence in BD.
Successful Invasions of Short Internally Deleted Elements (SIDEs) and Its Partner CR1 in Lepidoptera Insects

Abstract Although DNA transposons often generated internal deleted derivatives such as miniature inverted-repeat transposable elements, short internally deleted elements (SIDEs) derived from nonlong terminal-repeat retrotransposons are rare. Here, we found a novel SIDE, named Persaeus, that originated from the chicken repeat 1 (CR1) retrotransposon Zenon and it has been found widespread in Lepidoptera insects. Our findings suggested that Persaeus and the partner Zenon have experienced a transposition burst in their host genomes and the copy number of Persaeus and Zenon in assayed genomes are significantly correlated. Accordingly, the activity though age analysis indicated that the replication wave of Persaeus coincided with that of Zenon. Phylogenetic analyses suggested that Persaeus may have evolved at least four times independently, and that it has been vertically transferred into its host genomes. Together, our results provide new insights into the evolution dynamics of SIDEs and its partner non-LTRs.
Every aspect of advanced retinal imaging laser eyewear: principle, free focus, resolution, laser safety, and medical welfare applications

Retinal imaging laser eyewear has a miniature laser projector inside the frame which provides the wearer with digital image information through the pupil using the retina as a screen. Its principle is based on the geometric optics of the Maxwellian view combined with a parallel and narrow RGB laser beam. A prototype with the trademark of RETISSA® was invented with a miniature laser projector inside the glasses frame using a non-axisymmetric free-surface reflecting mirror. The image resolution was measured based on the visual acuity testing using a retinal projected image of Landolt ring for four subjects with the different naked visual acuity of 0.04, 0.5, 0.9 and 1.2. Also, the theoretical image resolution was studied based on the beam propagation simulation under the eyeball model. The results show how to achieve high resolution and free focus in proper balance by adjusting the laser beam characteristics of the beam diameter and divergence. On the laser safety, RETISSA® was found to be in the Class I category, which has the safety factor of over 700 in the RGB radiation intensity under the international standard of IEC60825-1. RETISSA® also met the thousand times more strict Class I criteria of FDA/CDRH 21CFR1040.10 with the total RGB radiation intensity of less than 0.37 μW, indicating its laser radiation is not considered to be hazardous as stated in the definition of FDA Class I. The experimental evidence that the radiation of RETISSA® is equal to or weaker than displays of conventional digital devices also provide its proof of safety, including its long-term use as one of daily digital devices. The potential of retinal laser imaging is mentioned for use in ophthalmology medicine. The current activity on the medical welfare applications as low vision aids and ophthalmic testing equipment is reviewed including clinical research and trials in Japan and Europe.
Thickness-Dependence Electrical Characterization of the One-Dimensional van der Waals TaSe3 Crystal

Needle-like single crystalline wires of TaSe3 were massively synthesized using the chemical vapor transport method. Since the wedged-shaped single TaSe3 molecular chains were stacked along the b-axis by weak van der Waals interactions, a few layers of TaSe3 flakes could be easily isolated using a typical mechanical exfoliation method. The exfoliated TaSe3 flakes had an anisotropic planar structure, and the number of layers could be controlled by a repeated peeling process until a monolayer of TaSe3 nanoribbon was obtained. Through atomic force and scanning Kelvin probe microscope analyses, it was found that the variation in the work function with the thickness of the TaSe3 flakes was due to the interlayer screening effect. We believe that our results will not only help to add a novel quasi-1D block for nanoelectronics devices based on 2D van der Waals heterostructures, but also provide crucial information for designing proper contacts in device architecture.