Miracle-dz/UniFAR-FTUs huggingface dataset:
Machine learning suggests sleep as a core factor in chronic pain.

Patients with chronic pain have complex pain profiles and associated problems. Subgroup analysis can help identify key problems. We used a data-based approach to define pain phenotypes and their most relevant associated problems in 320 patients undergoing tertiary pain management. Unsupervised machine learning analysis of parameters "pain intensity", "number of pain areas", "pain duration", "activity pain interference" and "affective pain interference", implemented as emergent self-organizing maps, identified three patient phenotype clusters. Supervised analyses, implemented as different types of decision rules, identified "affective pain interference" and the "number of pain areas" as most relevant for cluster assignment. These appeared 698 and 637 times, respectively, in 1000 cross-validation runs among the most relevant characteristics in an item categorization approach in a computed ABC analysis. Cluster assignment was achieved with a median balanced accuracy of 79.9%, a sensitivity of 74.1%, and a specificity of 87.7%. In addition, among 59 demographic, pain etiology, comorbidity, lifestyle, psychological, and treatment-related variables, sleep problems appeared 638 and 439 times among the most important characteristics in 1000 cross-validation runs where patients were assigned to the two extreme pain phenotype clusters. Also important were the parameters "fear of pain", "self-rated poor health", and "systolic blood pressure". Decision trees trained with this information assigned patients to the extreme pain-phenotype with an accuracy of 67%. Machine learning suggested sleep problems as key factors in the most difficult pain presentations, therefore deserving priority in the treatment of chronic pain.
Pyrroloquinoline quinone can prevent chronic heart failure by regulating mitochondrial function.

Background Myocardial mitochondrial dysfunction is the leading cause of chronic heart failure (CHF). Increased reactive oxygen species (ROS) levels, disruption of mitochondrial biogenesis and mitochondrial Ca2+([Ca2+]m) homeostasis and reduction of the mitochondrial membrane potential (ΔΨm) cause myocardial mitochondrial dysfunction. Therefore, treating CHF by targeting mitochondrial function is a focus of current research. For the first time, this study investigated the effects of the strong antioxidant pyrroloquinoline quinone (PQQ) on mitochondrial function in a cardiac pressure overload model, and the mechanism by which PQQ regulates [Ca2+]m homeostasis was explored in depth. Methods After transaortic constriction (TAC), normal saline and PQQ (0.4, 2 and 10 mg/kg) were administered intragastrically to Sprague Dawley (SD) rats for 12 weeks. In vitro, neonatal rat left ventricle myocytes (NRVMs) were pretreated with 200 nm angiotensin II (Ang II) with or without PQQ (1, 10 and 100 μM). Rat heart remodelling was verified by assessment of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels (qRT-PCR), cell surface area (wheat germ agglutinin (WGA) staining in vivo and α-actin in vitro) and echocardiography. Myocardial mitochondrial morphology was assessed by transmission electron microscopy. Western blotting was used to assess mitochondrial biogenesis [peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and transcription factor A, mitochondrial (TFAM)]. The ΔΨm was determined by tetraethyl benzimidazolyl carbocyanine iodide (JC-1) staining and flow cytometry, and ROS levels were measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) and MitoSOX Red staining. [Ca2+]m was measured by isolating rat mitochondria, and mitochondrial Ca2+ channel proteins [the mitochondrial Na+/Ca2+ exchanger (NCLX) and mitochondrial Ca2+ uniporter (MCU)] were detected by Western blot. Results In vivo and in vitro, PQQ pretreatment improved pressure overload-induced cardiac remodelling and cell hypertrophy, thus preventing the occurrence of CHF. PQQ also prevented mitochondrial morphology damage and reduced the PGC-1α and TFAM downregulation caused by TAC or Ang II. In addition, in NRVMs treated with Ang II + PQQ, PQQ regulated ROS levels and increased the ΔΨm. PQQ also regulated [Ca2+]m homeostasis and prohibited [Ca2+]m overloading by increasing NCLX expression. Conclusions These results show that PQQ can prevent [Ca2+]m overload by increasing NCLX expression and thereby reducing ROS production and protecting the ΔΨm. At the same time, PQQ can increase PGC-1α and TFAM expression to regulate mitochondrial biogenesis. These factors can prevent mitochondrial dysfunction, thereby reducing cardiac damage caused by pressure overload and preventing the occurrence of CHF.
Resolution Recovery with Pre-Reconstruction Fourier Transforms Filtering for a High Resolution Animal SPECT System

Purpose: Spatial resolution and accurate quantification in animal SPECT plays a critical role in preclinical imaging. Appropriate Projections filtering can help to address the issue of resolution compensation and recovery coefficients. The main aim of current study was to explore a new version of MLEM algorithm with pre-reconstruction Fourier transform filtering to improve the Recovery Coefficient RC by filtering the projections. Materials and Methods: A complete set of measurements was performed using HiReSPECT system. Different phantom studies were performed using point sources, NEMA NU 4 and dedicated hot rod phantom. All data was reconstructed using the developed Maximum-Likelihood Expectation-Maximization (MLEM) algorithm with and without resolution recovery information and also with our presented pre-reconstruction Fourier transform filter. Image quality was assessed by different parameters such as Coefficient Of Variation (COV), Recovery Coefficient (RC) and FWHM. Results: FWHM in tangential direction was improved 0.6 and 0.2 for our presented algorithm against MLEM without and with CDRF, respectively. Fourier filtering image led to improvement of image quality where hot rods with 1.6 and 1.8 mm in diameter could be recognized clearly in our presented algorithm in dedicated hot rod phantom. Our presented algorithm resulted in rapid convergence and growth of RC in lower iteration. Conclusion: The purpose of the current study was to introduce new pre-reconstruction filter. The results of this investigation showed that the inclusion of our proposed filter can lead to better image quality and quantification in lower iteration. These data suggest that current filter can provide higher RC in lower iteration.
Management of small-incision lenticule extraction ectasia using tissue addition and pocket crosslinking.

The feasibility of managing ectasia after small-incision lenticule extraction (SMILE) using tissue addition and pocket collagen crosslinking (CXL) is described. Four eyes of 3 patients (mean age 25.7 years) developed features of keraectasia at a mean period of 3 years after SMILE for myopia. All cases were managed with insertion of heterologous SMILE lenticules in the previously created pocket, followed by simultaneous accelerated CXL. At a mean follow-up of 7.67 months, there was an improvement in corrected distance visual acuity and reduction in keratometry and higher-order aberrations in all eyes. The visual, refractive, and topographic parameters remained stable at the last visit compared to the 2-week follow-up visit. No eye developed haze, infection, or rejection requiring tissue explantation. Early experience showed tissue addition with simultaneous pocket CXL to be a feasible approach for managing ectasia after SMILE. However, further follow-up is required to establish the long-term safety and effects on corneal stabilization.
Fixation of Unstable Osteochondritis Dissecans Lesions and Displaced Osteochondral Fragments Using New Biodegradable Magnesium Pins in Adolescents

Objective Fixation of unstable osteochondritis dissecans (OCD) lesions and displaced osteochondral fragments are frequently performed procedures in pediatric orthopedic surgery. Since 2018, CE-certified MAGNEZIX pins are used in our institution in these cases. The aim of this study was (1) to analyze safety, efficiency, and limitations of magnesium-pin-based fixation of unstable OCD lesions and displaced osteochondral fragments and (2) to report clinical and radiological outcomes at short-term follow-up (FU). Design In this prospective cohort study, 19 patients (10 girls and 9 boys) were included. Inclusion criteria were (1) magnetic resonance imaging–confirmed unstable OCD lesion or displaced osteochondral fragment, (2) fixation with magnesium-based pins, and (3) minimum FU of 6 months. X-rays were taken 6 weeks and 6 months after operation and magnetic resonance imaging scans every 4 to 6 months to assess the healing progress. Results In total 67 pins were used, with a mean of 3.6 ± 1.4 per patient. Average age at surgery was 13.7 years (11-17 years). Mean time of operation was 56 ± 31 minutes, including arthroscopy, fixation, and patellar realignment (n = 6). No intraoperative complications occurred. Average FU was 11.3 ± 4.2 months (6-20 months). No redislocation or new dislocation occurred. Until now a complete radiographic healing occurred in 12 cases. Due to an implant failure in one case 11 weeks after the index surgery a revision became necessary. Conclusions In short-term FU of 11 ± 4 months MAGNEZIX pins provide high stability after fixation of unstable OCDs and displaced osteochondral fragments leading to uncomplicated and timely healing.
Inclusive inheritance for residual feed intake in pigs and rabbits

Abstract Non‐genetic information (epigenetic, microbiota, behaviour) that results in different phenotypes in animals can be transmitted from one generation to the next and thus is potentially involved in the inheritance of traits. However, in livestock species, animals are selected based on genetic inheritance only. The objective of the present study was to determine whether non‐genetic inherited effects play a role in the inheritance of residual feed intake (RFI) in two species: pigs and rabbits. If so, the path coefficients of the information transmitted from sire and dam to offspring would differ from the expected transmission factor of 0.5 that occurs if inherited information is of genetic origin only. Two pigs (pig1, pig2) and two rabbits (rabbit1, rabbit2) datasets were used in this study (1,603, 3,901, 5,213 and 4,584 records, respectively). The test of the path coefficients to 0.5 was performed for each dataset using likelihood ratio tests (null model: transmissibility model with both path coefficients equal to 0.5, full model: unconstrained transmissibility model). The path coefficients differed significantly from 0.5 for one of the pig datasets (pig2). Although not significant, we observed, as a general trend, that sire path coefficients of transmission were lower than dam path coefficients in three of the datasets (0.46 vs 0.53 for pig1, 0.39 vs 0.44 for pig2 and 0.38 vs 0.50 for rabbit1). These results suggest that phenomena other than genetic sources of inheritance explain the phenotypic resemblance between relatives for RFI, with a higher transmission from the dam's side than from the sire's side.
Short communication. Evaluation of a commercial kit based on acridine orange/propidium iodide to assess the plasma membrane integrity of ram sperm

This study was designed to develop a semiautomatic computer assisted methodology to evaluate the membrane integrity of ram spermatozoa using a commercial kit based on acridine orange/propidium iodide (AO/PI) labelling and ImageJ software. The study was divided into two experiments. In the first trial, the new computer-assisted method was validated by mixing fresh semen samples with different volumes of freeze killed spermatozoa to determine proportions of damaged spermatozoa in the final samples. The proportion of damaged spermatozoa in each sample determined by the automated procedure where highly correlated (R2=0.97, p<0.001) with the predicted theoretical values. In the second trial, the new method was compared with a previously validated method of membrane integrity assessment based on phase-contrast/propidium iodide (PH/PI) methodology. Measurements by AO/PI were, on average, 4.0% larger than measurements by PH/PI (SD=7.02%) and 1.79% smaller than measurements of sperm motility determined by CASA (SD=4.83). The AO/PI method was also more repeatable than the PH/PI. The double staining methodology coupled with the routine for image analysis allowing automatic determination of sperm membrane integrity means a reduction in processing time of 75% compared to the previously developed method using a single fluorochrome (3 vs 12 min on average if the incubation period was included). This facilitates its use when a large number of samples are analysed. Our results validate the new computer assisted method for assessing sperm membrane integrity in sheep. The new method developed, in addition to being a free tool, allows quick automatic determination of sperm viability, which facilitates its use in routine semen analysis.
Hypervisor-Based Protection of Code

The code of a compiled program is susceptible to reverse-engineering attacks on the algorithms and the business logic that are contained within the code. The main existing countermeasure to reverse-engineering is obfuscation. Generally, obfuscation methods suffer from two main deficiencies: 1) the obfuscated code is less efficient than the original and 2) with sufficient effort, the original code may be reconstructed. We propose a method that is based on cryptography and virtualization. The most valuable functions are encrypted and remain inaccessible even during their execution, thus preventing their reconstruction. A specially crafted hypervisor is responsible for decryption, execution, and protection of the encrypted functions. We claim that the system can provide protection even if the attacker: 1) has access to the operating system kernel and 2) can intercept communication over the system bus. The evaluation of the system’s efficiency suggests that it can compete with and outperform obfuscation-based methods.
3-Pyridinylboronic acid normalizes the effects of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure in zebrafish embryos

Abstract 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is a neurotoxin that damages dopaminergic neurons. Zebrafish has been shown to be a suitable model organism to investigate the molecular pathways in the pathogenesis of Parkinson’s disease and also for potential therapeutic agent research. Boron has been shown to play an important role in the neural activity of the brain. Boronic acids are used in combinatorial approaches in drug design and discovery. The effect of 3-pyridinylboronic acid which is an important sub-class of heterocyclic boronic acids has not been evaluated in case of MPTP exposure in zebrafish embryos. Accordingly, this study was designed to investigate the effects of 3-pyridinylboronic acid on MPTP exposed zebrafish embryos focusing on the molecular pathways related to neurodegeneration and apoptosis by RT-PCR. Zebrafish embryos were exposed to MPTP (800 μM); MPTP + Low Dose 3-Pyridinylboronic acid (50 μM) (MPTP + LB) and MPTP + High Dose 3-Pyridinylboronic acid (100 μM) (MPTP + HB) in well plates for 72 hours post fertilization. Results of our study showed that MPTP induced a P53 dependent and Bax mediated apoptosis in zebrafish embryos and 3-pyridinylboronic acid restored the locomotor activity and gene expressions related to mitochondrial dysfunction and oxidative stress due to the deleterious effects of MPTP, in a dose-dependent manner.
Antimalarial-agent artemisinin and derivatives portray more potent binding to Lys353 and Lys31-binding hotspots of SARS-CoV-2 spike protein than hydroxychloroquine: potential repurposing of artenimol for COVID-19

Abstract Medicinal herbs have proved along history to be a source of multiple cures. In this paper, we demonstrate how hydroxychloroquine can act as a good inhibitor of SARS-CoV-2 Spike protein receptor-binding-domain using molecular docking studies. We also unveil how hydroxychloroquine can interfere in the prevention of Lys353 in hACE2 from interacting with the corresponding binding hotspot present on the Spike protein. Further screening of artemisinin & derived compounds produced better Vina docking score than hydroxychloroquine (-7.1 kcal mol−1 for artelinic acid vs. −5.5 kcal mol−1 for hydroxychloroquine). Artesunate, artemisinin and artenimol, showed two mode of interactions with Lys353 and Lys31 binding hotspots of the Spike protein. Molecular dynamics analysis confirmed that the formed complexes are able to interact and remain stable in the active site of their respective targets. Given that these molecules are effective antivirals with excellent safety track records in humans against various ailment, we recommend their potential repurposing for the treatment of SARS-CoV-2 patients after successful clinical studies. In addition, an extraction protocol for artemisinin from Artemisia annua L. is proposed in order to cope with the potential urgent global demand. Communicated by Ramaswamy H. Sarma GRAPHICAL ABSTRACT Highlights Hydroxychloroquine role to prevent hACE2 from interacting with SARS-CoV-2 Spike protein is unveiled Artemisinin & derivatives entangle Lys353 & Lys31 binding hotspots of virus Spike protein and prevent infection Artemisinin, artesunate and artenimol stand as strong repurposing cadidates for COVID-19 clinical trials
Knowledge of, and attitudes to, shared decision-making in orthodontics in the UK

Objective: To establish UK orthodontic treatment providers’ knowledge of, and attitudes to, shared decision-making (SDM). SDM involves patients as equal partners in decisions about treatment. Design: Cross-sectional survey. Setting: Online survey across the UK. Population: Dentists and orthodontists providing orthodontic treatment in the UK. Methods: Potential participants were contacted through the British Orthodontic Society mailing lists. An online survey was developed to examine knowledge of, and attitudes to, SDM using a combination of evidence-based statements and free text boxes. Questions regarding previous training in SDM and preferences for further training were also included. Results: The survey was completed by 210 respondents, yielding an approximate response rate of 15%. Respondents were mainly consultants (34%) and specialist orthodontists (42%). SDM was well described in terms of the people involved in this process, how it is approached, the components and topics of discussion, and the overall purpose of SDM. Generally, there was consistency in attitudinal responses, with the largest variance in responses to questions about the professional–patient partnership, the interface between SDM and clinical guidelines, and accepting a decision that is discordant with the professional’s opinion. Fifty-one respondents reported having some previous teaching/training in SDM, with the majority (87%) indicating that they would like more training. Conclusion: Clinicians providing orthodontic treatment in the UK have a good understanding of the meaning of shared decision-making. Concerns raised about using SDM and knowledge gaps suggest there is value in providing SDM training for the orthodontic team and that orthodontic providers would welcome it.
CrowdTracking: Real-Time Vehicle Tracking Through Mobile Crowdsensing

Traditionally, vehicle tracking is accomplished using predeployed video camera networks, which relies on stationary cameras and searches for the target vehicle from videos. In this paper, we develop CrowdTracking, i.e., a crowd tracking system that people can collaboratively keep track of the moving vehicle by taking photographs, especially in areas where video cameras are deficient. In other words, the underlying support of CrowdTracking is mobile crowdsensing. Several novel ideas underpin CrowdTracking. First, the vehicle can be rapidly localized by using both photographing contexts (including the location and the shooting direction) of the photographer and the road network. Second, the moving speed of the vehicle can be estimated according to two localization results and the trajectory will be predicted. As a result, through continuously collecting photographs of the moving vehicle on different roads, the vehicle can be tracked and localized almost in real time. Through precisely localizing the specified vehicle, two optimization objectives are met: 1) maximizing the tracking coverage to the vehicle’s actual trajectory and 2) minimizing the number of participants who are assigned vehicle-tracking tasks. We evaluate the localization method with a real dataset and report about 6 m error. We also evaluate the vehicle-tracking method of CrowdTracking using a synthetic data set and experimental results validate its effectiveness and efficiency.
Universal Controllers for Architecture Simulation

For optimization studies of dynamical systems, it is common practice to model and tune local controllers for miscellaneous subsystems. For instance, a model of a chemical plant may contain a valve motor model, and a model of a PID controller may be included to control the motor. The associated controller tuning effort is ultimately wasted. The actual controller will be retuned anyway after finalization of the system design, or will be structurally different. For this reason, control algorithms are needed that just provide the functionality of the actual control algorithm that will be designed in a later phase of the system design. These temporary algorithms need to have low tuning requirements, and it must be possible for non-controlspecialist to generate them. On the other hand, they only need to function inside a simulation environment. Several mainstream control approaches are reviewed, and boundary layer sliding mode control is proposed as a suitable approach for this kind of task. This class of controllers can be used without any tuning effort, and is able to compete with tuned PID-controllers in terms of tracking performance. An end-user friendly implementation of a universal controller in the equation-based and object-oriented modelling language Modelica is presented. Several examples are shown to demonstrate the performance of the proposed approach.
Alteration of Iron Level in Drinking Water by Aeration in Gonbad Kavoos (North East of Iran)

Problem statement: In this study, removal of iron was surveyed in well water in Gonbad Kavoos City. Approach: Samples were taken before and after aeration. Concentration of iron in each sample was measured by spectrophotometer. Results: The results showed that the iron concentration was decreased after aeration (0.55, 0.44, 0.44, 0.46, 0.40 and 0.41 mg L-1) when compared with before aeration of water (0.64, 0.68, 0.65, 0.62, 0.65 and 0.67 mg L-1), respectively. Conclusion: It was concluded that using aeration technology can reduce iron concentration conform to internationally approved guidelines for iron.