Miracle-dz/UniFAR-FTUs huggingface dataset:
Scale-Free Amplitude Modulation of Low-Frequency Fluctuations in Episodic Migraine.

Arrhythmic fluctuations in neural activity occur at many levels of the nervous system. Such activity does not have a characteristic temporal periodicity but can exhibit statistical similarities, most commonly power-law scaling behavior, which is indicative of scale-free dynamics. The recurrence of scaling laws across many different systems and its manifestation in behavior has prompted a search for unifying principles in human brain function. With this in mind, a focused search for abnormities in scale-free dynamics is of considerable clinical relevance to migraine and other clinical pain disorders. Here we examined the scale-free properties of the resting-state fMRI signal in the broadband frequency range known to be related to spontaneous neural activity (0.01-0.1Hz). In a large cohort of episodic migraine patients (N=40), we observed that the strength of long-range temporal correlations in the fMRI signal (captured by the scaling exponent α) was significantly higher in the sensorimotor network compared to healthy controls. Increases in the scaling exponent were positively correlated with fMRI signal variance and negatively correlated with patient's self-reported headache intensity. These changes in the fMRI signal suggest that the temporal structure of amplitude fluctuations carries valuable information about the dynamic state of the underlying neuronal networks and ensuing sensory impairments in migraine. The demonstrated scaling laws pose a novel quantitative approach for examining clinically relevant inter-individual variability in migraine and other pain disorders.
Using bispecific antibodies in forced degradation studies to analyze the structure–function relationships of symmetrically and asymmetrically modified antibodies

ABSTRACT Forced degradation experiments of monoclonal antibodies (mAbs) aid in the identification of critical quality attributes (CQAs) by studying the impact of post-translational modifications (PTMs), such as oxidation, deamidation, glycation, and isomerization, on biological functions. Structure-function characterization of mAbs can be used to identify the PTM CQAs and develop appropriate analytical and process controls. However, the interpretation of forced degradation results can be complicated because samples may contain mixtures of asymmetrically and symmetrically modified mAbs with one or two modified chains. We present a process to selectively create symmetrically and asymmetrically modified antibodies for structure-function characterization using the bispecific DuoBody® platform. Parental molecules mAb1 and mAb2 were first stressed with peracetic acid to induce methionine oxidation. Bispecific antibodies were then prepared from a mixture of oxidized or unoxidized parental mAbs by a controlled Fab-arm exchange process. This process was used to systematically prepare four bispecific mAb products: symmetrically unoxidized, symmetrically oxidized, and both combinations of asymmetrically oxidized bispecific mAbs. Results of this study demonstrated chain-independent, 1:2 stoichiometric binding of the mAb Fc region to both FcRn receptor and to Protein A. The approach was also applied to create asymmetrically deamidated mAbs at the asparagine 330 residue. Results of this study support the proposed 1:1 stoichiometric binding relationship between the FcγRIIIa receptor and the mAb Fc. This approach should be generally applicable to study the potential impact of any modification on biological function.
The design and evaluation of a novel low‐cost portable ventilator

Modern mechanical ventilator technologies broadly consist of digitally‐controlled electronic devices and analogue systems driven by compressed gas sources. Drawbacks such as high cost, complex maintenance and the need for cumbersome sources of compressed driving gas hinder adoption in pre‐hospital and low‐resource environments. We describe the evaluation and testing of a simple, low‐cost alternative ventilator that uses a novel pressure‐sensing approach and control algorithm. This is designed to provide portable positive‐pressure mechanical ventilation at a reduced cost, while autonomously monitoring patient condition and important safety parameters. A prototype ventilator was constructed and evaluated using an anaesthetic test‐lung as a patient surrogate. Using a modifiable test‐lung and digital pressure sensor, we investigated ventilation pressure waveform circuit leak detection, and compliance and resistance change detection. During intermittent positive‐pressure ventilation to the test‐lung, the prototype system showed acceptable pressure waveform parameters: all simulated circuit leaks ≥ 6 mm2 in size were detected; compliance changes were detected between 10 ml.cmH2O−1, 20 ml.cmH2O−1 and 50 ml.cmH2O−1; and resistance changes were detected across the available simulated range. These results show this prototype technology has the potential to provide safe emergency ventilation without the use of any complex digital sensors or software while its construction and design enables significant reductions in cost and complexity. The study suggests further work is now justified in progressing the technology to clinical trials.
Impact of IL12B Polymorphisms on Genetic Susceptibility and IL-12p40 and IL-23 Serum Levels in Rheumatoid Arthritis

ABSTRACT The aim of this study was to evaluate the possible association of IL12B gene polymorphisms with serum levels of IL-12p40, IL-23 and genetic susceptibility to rheumatoid arthritis (RA) in the Bulgarian population. Genotyping for IL12Bpro (rs17860508) and IL12B A/C − 3ʹ UTR (rs3212227) polymorphisms was performed by polymerase chain reaction (PCR)-based methods in 125 RA patients and 239 healthy controls. The IL-23 and IL-12p40 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). An association was established between the rs17860508 polymorphism and RA susceptibility in Bulgarian population with an increased frequency of rs17860508 minor allele-2 and homozygous genotype-22 in RA patients. The rs17860508 risk RA genotype-22 was also significantly correlated to elevated serum IL-23 in RA patients. Although, there was no association between the rs3212227 and genetic predisposition to RA, significantly increased serum levels of both Il-12p40 and IL-23 were observed in RA patients with the rs3212227 AA genotype. Furthermore, the distribution of haplotypes and genotype combination in our cohort indicated increased RA risk in individuals carrying the rs17860508/rs3212227 2/A haplotype or 2.2/AC+CC combination, while 1/A haplotype or 1.1/AA combination may be protective for RA. In conclusion, our study demonstrates a functional effect of IL12B polymorphisms on IL-12p40 and IL-23 cytokine levels in RA patients and suggests a leading role for IL12B rs17860508 in the genetic predisposition to RA, while IL12B rs3212227 significantly modify the RA risk in Bulgarian population.
Automatic hand phantom map detection methods

Many amputees have maps of referred sensation from their missing hand on their residual limb (phantom maps). This skin area can serve as a target for providing amputees with tactile sensory feedback. Providing tactile feedback on the phantom map can improve the object manipulation ability, enhance embodiment of myoelectric prostheses users and help reduce phantom limb pain. The distribution of the phantom map varies with the individual. Here, we investigate a fast and accurate method for hand phantom map shape detection. We present three elementary (group testing, adaptive edge finding and support vector machines (SVM)) and two combined methods (SVM with majority-pooling and SVM with active learning) tested with different types of phantom map models and compare the classification error rates. The results show that SVM with majority-pooling has the smallest classification error rate.
PPAR Ligands Containing Stilbene Scaffold.

Peroxisome proliferator activated receptors (PPARs) are transcriptional factors belonging to the ligand-activated nuclear receptor superfamily. They are ubiquitously expressed throughout the body. So far, three major subtypes have been identified, PPAR, PPARand PPAR. They are crucial for lipid and glucose metabolism, and are also involved in the regulation of several types of tumors, inflammation, cardiovascular diseases and infertility. The importance of these transcription factors in physiology and pathophysiology has been largely investigated. Synthetic PPAR ligands are widely used in the treatment of dyslipidemia (e.g. fibrates - PPARα activators) or in diabetes mellitus (e.g. thiazolidinediones - PPARγ agonists) while new generation of dual agonists reveals hypolipemic, hypotensive, antiatherogenic, anti-inflammatory and anticoagulant action. Many natural ligands, including polyphenolic compounds, influence the expression of these receptors. They have several health-promoting properties, including antioxidant, anti-inflammatory, and antineoplastic activities. Resveratrol, a stilbene polyphenol, is a biological active modulator of several signaling proteins, including PPARs. Given the enormous pharmacological potential of resveratrol, stilbene-based medicinal chemistry has had a rapid increase covering various areas of research. The present review discusses about ligands of PPARs that contain stilbene scaffold and summarize the different types of compounds on the basis of chemical structure.
Intraluminal brachytherapy of de novo TIPS: a prospective randomized double-blind study.

OBJECTIVE The aim of this prospective double-blind and randomized study was to assess whether intraluminal brachytherapy of de novo transjugular intrahepatic portosystemic shunts (TIPS) can prevent significant shunt stenosis. SUBJECTS AND METHODS Forty patients with portal hypertension due to liver cirrhosis were enrolled. In the irradiation group of 20 patients, the gamma radiation source, iridium-192, was introduced into the shunt within a special balloon catheter that allows the radionuclide to be centered within the shunt. A dose of 14 Gy in the shunt wall at a depth of 2 mm should be achieved. In the control group of 20 patients, a dummy source was used. Doppler sonography was performed immediately, 1 day, 1 week, 4 weeks, and 3 months after TIPS placement and then at an interval of 3 months during the first year. The primary end point of the study was the percentage of patients who developed significant shunt stenosis, defined as a reduction of maximum flow velocity below 50 cm/sec in the proximal part of the shunt 1 cm from the entry of the stent into the punctured portal vein branch. Fisher's exact test was used. RESULTS The TIPS procedure was technically successful in all patients. Seventeen patients in the irradiation group and 15 patients in the control group were followed up. Five patients (29.4%) in the irradiation group and 10 (66.7%) in the control group developed significant shunt stenosis during the first year after TIPS placement (p = 0.0392). The time until such stenosis occurred did not differ significantly between the two groups. CONCLUSION Our results suggest that brachytherapy can be useful in reducing the incidence of TIPS stenosis. A larger study with histopathologic analysis may be needed to confirm these findings.
Inhibitory Effects of Quercetin and Its Human and Microbial Metabolites on Xanthine Oxidase Enzyme

Quercetin is an abundant flavonoid in nature and is used in several dietary supplements. Although quercetin is extensively metabolized by human enzymes and the colonic microflora, we have only few data regarding the pharmacokinetic interactions of its metabolites. Therefore, we investigated the interaction of human and microbial metabolites of quercetin with the xanthine oxidase enzyme. Inhibitory effects of five conjugates and 23 microbial metabolites were examined with 6-mercaptopurine and xanthine substrates (both at 5 μM), employing allopurinol as a positive control. Quercetin-3′-sulfate, isorhamnetin, tamarixetin, and pyrogallol proved to be strong inhibitors of xanthine oxidase. Sulfate and methyl conjugates were similarly strong inhibitors of both 6-mercaptopurine and xanthine oxidations (IC50 = 0.2–0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC50 = 1.8 μM) with higher potency vs. 6-MP oxidation (IC50 = 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC50 = 0.2–0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC50 = 7.0 μM), and induced more potent inhibition compared to quercetin (IC50 = 1.4 μM). These observations highlight that some quercetin metabolites can exert similar or even a stronger inhibitory effect on xanthine oxidase than the parent compound, which may lead to the development of quercetin–drug interactions (e.g., with 6-mercaptopurin or azathioprine).
The Influence of Social Support and Care Burden on Depression among Caregivers of Patients with Severe Mental Illness in Rural Areas of Sichuan, China

Depression is one of the most common psychological consequences of caregiving. Caring for patients with severe mental illness (SMI) adds significant challenges to family caregivers’ mental health. The purpose of this study was to describe the prevalence of depression among caregivers of SMI patients in rural areas of Sichuan province of China, to examine the influence of social support and care burden on depression, and to explore the intermediary effect of care burden between social support and depression among caregivers of SMI patients. Data were collected from 256 primary caregivers of SMI patients in rural Sichuan Province in China. We used structural equation modeling (SEM) to test the hypothesized relationship among the variables. We found that a total of 53.5% of caregivers had depression. Both care burden (β = 0.599, 95%CI: 0.392–0.776) and social support (β = −0.307, 95%CI: (−0.494)–(−0.115)) were directly related to depression, while social support had a direct association with care burden (β = −0.506, 95%CI: (−0.672)–(−0.341)). Care burden mediated the relationship between social support and depression. For the socio-demographic variables, gender, education level and per capita annual income of household had significant correlations with depression (p < 0.05). The results strongly demonstrated that social support and care burden were predictors of depression, especially social support. Policymakers should fully recognize the role of primary family caregivers in caring for SMI patients and promote interventions to decrease care burden and reduce caregivers’ depression by improving social support and network. More attention should be given to female caregivers and caregivers with lower education and lower household income levels.
Mung Bean (Vigna radiata L.): Bioactive Polyphenols, Polysaccharides, Peptides, and Health Benefits

Mung bean (Vigna radiata L.) is an important pulse consumed all over the world, especially in Asian countries, and has a long history of usage as traditional medicine. It has been known to be an excellent source of protein, dietary fiber, minerals, vitamins, and significant amounts of bioactive compounds, including polyphenols, polysaccharides, and peptides, therefore, becoming a popular functional food in promoting good health. The mung bean has been documented to ameliorate hyperglycemia, hyperlipemia, and hypertension, and prevent cancer and melanogenesis, as well as possess hepatoprotective and immunomodulatory activities. These health benefits derive primarily from the concentration and properties of those active compounds present in the mung bean. Vitexin and isovitexin are identified as the major polyphenols, and peptides containing hydrophobic amino acid residues with small molecular weight show higher bioactivity in the mung bean. Considering the recent surge in interest in the use of grain legumes, we hope this review will provide a blueprint to better utilize the mung bean in food products to improve human nutrition and further encourage advancement in this field.
Fabrication of Various Plasmonic Pt Nanostructures via Indium Assisted Solid-State Dewetting: From Small Nanoparticles to Widely Connected Networks

In this paper, the modified solid-state dewetting (MSSD) of well-defined and various uniform Pt nanostructures is demonstrated by the auxiliary diffusion enhancement. The MSSD utilizes the introduction of metallic indium (In) layers with high diffusivity in between sapphire and platinum (Pt) layer, through which the global diffusion and dewetting of metallic atoms can be significantly enhanced. Subsequently, the In atoms can be sublimated from the NP matrix, resulting in the formation of pure Pt NPs. By the systematic control of In and Pt bi-layer thickness, various areal density, size and configuration of Pt NPs are demonstrated. The In2 nm/Pt2 nm bilayers establish very small and highly dense NPs throughout the temperature range due to the early maturation of growth. Intermediate size of NPs is demonstrated with the In45 nm/Pt15 nm bilayers with the much improved interparticle spacings by annealing between 650 and 900 °C for 450 s. Finally, the In30 nm/Pt30 nm bilayers demonstrate the widely connected network-like nanostructures. In addition, the finite difference time domain (FDTD) simulation is employed to exploit the local electric field distributions at resonance wavelengths. The dewetting characteristics of In/Pt bilayers is systematically controlled by the modifications of layer thickness and annealing temperature and is systematically described based on the diffusion of atoms, Rayleigh instability and surface energy minimization mechanism. The optical properties demonstrate dynamic and widely tunable localized surface plasmon resonance (LSPR) responses depending upon the various surface morphologies of Pt nanostructures.
Deco: A Decentralized, Cooperative Atomic Commit Protocol

An atomic commit protocol can cause long-term locking of databases if the coordinator crashes or becomes disconnected from the network. In this paper we describe how to eliminate the coordinator. This decentralized, cooperative atomic commit protocol piggybacks transaction statuses of all transaction participants onto tokens which are passed among the participants. Each participant uses the information in the tokens to make a decision of when to go to the next state of a three-phase commit protocol. Transactions can progress to ensure a uniform agreement on success or failure, even if the network is partitioned or nodes temporarily crash.
Rapsyn facilitates recovery from desensitization in fetal and adult acetylcholine receptors expressed in a muscle cell line

The physiological significance of the developmental switch from fetal to adult acetylcholine receptors in muscle (AChRs) and the functional impact of AChR clustering by rapsyn are not well studied. Using patch clamp experiments, we show that recovery from desensitization is faster in the adult AChR isoform. Recovery from desensitization is determined by the AChR isoform‐specific cytoplasmic M3–M4 domain. The co‐expression of rapsyn in muscle cells induced AChR clustering and facilitated recovery from desensitization in both fetal and adult AChRs. In fetal AChRs, facilitation of recovery kinetics by rapsyn was independent of AChR clustering. These effects could be crucial adaptations to motor neuron firing rates, which, in rodents, have been shown to increase around the time of birth when AChRs cluster at the developing neuromuscular junctions.
Clinical Outcomes of Metachronous Gastric Cancer after Endoscopic Resection for Early Gastric Cancer

Background/Aims Patients treated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) are at risk of developing metachronous gastric cancer (MGC). The aim of this study was to evaluate the clinical outcomes of MGC after ESD for EGC between the re-ESD and surgery groups. Methods In total, data from 1,510 patients who underwent ESD for EGC from January 2005 to May 2014 were retrospectively reviewed, and data from 112 patients with MGC were analyzed according to the type of treatment, namely, re-ESD and surgery. The clinicopathological factors affecting the subsequent treatment and outcomes of MGC were evaluated. Results The median duration to the development of MGC was 47 months. In multivariate analysis, lower body mass index (BMI) (p=0.037) and multiplicity (p=0.014) of index cases were significantly associated with subsequent surgery for MGC. In cases of MGC, a diffuse or mixed-type Lauren classification (p=0.009), the depth of tumor mucosal invasion (p=0.001), and an upper stomach location (p=0.049) were associated with surgery. Overall survival was significantly shorter in the surgery group than in the re-ESD group after treatment for MGC (log-rank test, p=0.01). Conclusions Lower BMI and multiplicity of index cancers were significantly associated with the surgical resection of MGC. Close follow-up is needed to minimize additional treatment for cases at high risk of advanced MGC after ESD for EGC.
The effects of educational interventions on suicide: A systematic review and meta-analysis

Background: Suicide is a major public health problem. Educational interventions for preventing suicidal behaviour are widely used, although little is known regarding the collective effectiveness of these interventions. Aim: We evaluated the existing evidence for the effectiveness of education interventions in the prevention of suicidal behaviour. Methods: In this systematic review and meta-analysis, we searched multiple databases using terms related to suicide prevention. The articles were reviewed by two independent reviewers, and the quality of evidence was rated according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data from individual studies were combined in meta-analyses. Results: We identified 41 studies evaluating two different types of interventions: school-based education interventions and gatekeeper training. Education interventions showed significant gains in terms of knowledge and attitudes, though the effects seem to vary depending on subjects’ personal characteristics. School-based education interventions significantly reduced suicidal ideation and suicide attempts in youths. Gatekeeper training showed no significant effect on suicide attempts or gatekeeper skills, though the quality of evidence for the estimate, according to GRADE criteria, was rated as very low. Conclusion: The results of this study indicate that school-based education interventions are effective in preventing suicidal ideation and suicide attempts. In clinical practice, as well as in research, the development and implementation of educational interventions should focus on participants’ individual characteristics.
Concurrent detection of soft errors based on current monitoring

Transient faults in future ICs turns to be a major consideration as the silicon process scales down. In this paper we propose a new soft error detecting technique with low area overhead, high detection speed and negligible performance penalty on the functional circuit under check. Among the already known techniques for soft error detection in logic circuits the proposed technique is the only one that is based on current monitoring.