Miracle-dz/UniFAR-FTUs huggingface dataset:
P2X receptor antagonists and their potential as therapeutics: a patent review (2010–2021)

ABSTRACT Introduction Purinergic receptors play a critical role in neurotransmission, and modulation of complex physiological functions and thus have implications in numerous disease states. The past decade has seen substantial progress in the design of novel chemical compounds that act on the P2X class of receptors and warrants an updated review of this field. Areas covered This review provides a summary of the patent literature describing the discovery and clinical uses of P2X receptor antagonists published between 2010 and September 2021. The reader will gain information on structural claims, representative structures, and biological data of recently reported P2X antagonists. Expert opinion Despite continual advancement in both crystallography and chemical biology strengthening our understanding of purinergic signalling, there remains an absence of clinically approved chemotypes. A testament to both the therapeutic potential and academic perseverance in purinergic research is the multitude of research initiatives that maintain active P2X receptor programs that have spanned decades. Very recently, the FDA declined Merck Pharmaceuticals application for Gefapixant, a P2X3 selective inhibitor as a treatment for chronic cough, requesting additional data. This unfortunate setback will ultimately be insignificant considering the long history of P2X investigation and the preclinical and clinical development that will undoubtedly occur over the next decade.
Long-term mitochondrial stress induces early steps of Tau aggregation by increasing reactive oxygen species levels and affecting cellular proteostasis

Accumulating evidence indicates that mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases. Both of these conditions are often associated with an increase in protein aggregation. However, still unknown are the specific defects of mitochondrial biology that play a critical role in the development of Alzheimer’s disease, in which Tau protein aggregates are observed in the brains of some patients. Here, we report that long-term mitochondrial stress triggered Tau dimerization, which is the first step of protein aggregation. Mitochondrial dysfunction was induced in HEK293T cells that received prolonged treatment with rotenone and in HEK293T cells with the knockout of NDUFA11 protein. To monitor changes in Tau protein aggregation, we took advantage of the bimolecular fluorescence complementation assay using HEK293T cells that were transfected with plasmids that encoded Tau. Inhibition of the ISR with ISRIB induced Tau dimerization, whereas ISR activation with salubrinal, guanabenz, and sephin1 partially reversed this process. Cells that were treated with ROS scavengers, N-acetyl-l-cysteine or MitoQ, significantly reduced the amount of ROS and Tau dimerization, indicating the involvement of oxidative stress in Tau aggregation. Our results indicate that long-term mitochondrial stress may induce early steps of Tau protein aggregation by affecting oxidative balance and cellular proteostasis.
Методика и автоматизированная система оценки взрываемости горных пород на карьерах

He technique of an estimation of explosibility of rocks on the open-cast mines, providing a remote (photometric) way of reception of the initial data about block structure of rocks in ledges of an open-cast mine and lumpiness of the blasted mass of rocks, mathematical modeling and computer technologies of processing of the information is stated, the characteristic of the automated system in which these technologies are realized.
Implementation of virtual reality technology to decrease patients' pain and nervousness during colonoscopies: a prospective randomised controlled single-blinded trial.

BACKGROUND Improved patient satisfaction in endoscopy is worthy of study as it is an invasive and potentially uncomfortable procedure. There is growing literature on patient satisfaction assessment in endoscopy as part of improving quality assurance. This study aimed to determine whether virtual reality (VR) technology can decrease patients' pain and nervousness during colonoscopies. METHODS Patients enrolled without sedation were randomly categorised into groups that watched VR (VR group; n=58) and those that did not watch VR (control group; n=59). The primary outcomes were pain score and skin conductance. Secondary endpoints included heart rate, systolic and diastolic arterial pressures, overall patient satisfaction, willingness to repeat the procedure, the difficulty of the procedure, the procedure duration, and bowel preparation. RESULTS The median (interquartile range (IQR)) pain scores were 7 (6-8) and 5 (4-6) in the control and VR groups, respectively (p<0.001). The median (IQR) skin conductance values after colonoscope insertion were 0.660 (0.490-0.840) and 0.390 (0.280-0.600) in the control and VR groups, respectively (p<0.001). Overall, patient satisfaction was significantly improved with the use of VR, along with a significant reduction in the difficulty perceived by the endoscopist. CONCLUSION VR technology helped to reduce patients' pain and nervousness and to improve patients' satisfaction during colonoscopies.
Sistema de medición de contaminación auditiva, empleando una red de sensores inalámbricos y sensores Ban

At the present time, noise pollution is a phenomenon that affects millions of people around the world. It causes several inconveniences because of automotive traffic, airplanes, construction equipment, factories, personal noise, and others. Noise pollution is an unpleasant noise created by people, electronic devices, or mechanical elements. Because of noise pollution, there are negative consequences such as hearing loss, stress, blood pressure changes, migraine, insomnia, nervous system problems, less productivity, mental health problems, and other difficulties. This graduation project presents a system that is able to measure noise pollution. It has a first step that includes a Wireless Sensor Network (WSN) that has nodes. The microcontroller ATmega328, which works in conjunction with a Global Positioning System (GPS), commands one of them. In addition, it has a sound level meter to measure noise, and a radio frequency device called XBee to transmit data to 1500 meters in length.
Changes in satisfaction with female genital self-image and sexual function after a Qigong exercise intervention in Spanish postmenopausal women: a randomized-controlled trial

Abstract Objective: To analyze the effectiveness of a Qigong exercise program on satisfaction with female genital self-image and female sexual function in postmenopausal Spanish women. Methods: A total of 49 women were randomly assigned to an experimental group (n = 22) that carried out training based on Qigong exercises for 12 weeks and a control group (n = 27) that did not carry out any type of intervention. Female genital self-image was measured through the Female Genital Self-Tmage Scale and female sexual function through the Female Sexual Function Tndex; both variables were measured before and just after the intervention. Results: Results showed that women who participated in the Qigong exercise program showed significant improvements with respect to female genital self-image, as well as in the domains of desire, arousal, lubrication, satisfaction, and pain and the total score of the Female Sexual Function Index, but, on the contrary, were not found in the orgasm domain. Conclusions: Our results suggest that Qigong has the potential to improve female genital self-image and female sexual function among postmenopausal Spanish women.
Investigation of the Experience of Immigrant Nurses in a Diverse Cultural Setting

ABSTRACT Background Work-related stress (WRS) is one of the most common stressors in healthcare workplace settings. Purpose This research study was designed to examine and discuss perceived WRS, job performance, social support, and the desire of immigrant nurses to work in a multicultural workplace. Methods A case research mixed-methodology approach, a quantitative survey, and semistructured qualitative interviews were used in this research study. Three hundred twenty-one respondents were invited, of which 246 (76.6%) returned valid questionnaires. A purposeful sampling technique was used in the qualitative portion of the study. A semistructured interviewing system was used on 20 nurses. Results “Workload” was the most common traumatic occurrence, whereas “treatment” and “death and dying” were the least common traumatic occurrences. Similarly, the mean of the social support scale, as defined using the McCain and Marklin Social Integration Scale, was moderate to high, suggesting that most of the participants received strong social support from their colleagues. The qualitative research found that the participants faced high pressures related to work and have struggled to acquire cultural skills, while having difficulties meeting their patients' cultural and spiritual needs and sustaining high-quality nursing care. Conclusions The findings of this study support that immigrant nurses working in the Kingdom of Saudi Arabia are stressed. A significant difference between the qualitative and quantitative results was found. The findings further contribute to our understanding of WRS, social support, job performance, and intention to stay among immigrant nurses in the Kingdom of Saudi Arabia.
Calmodulin Binding Activates Chromobacterium CopC Effector to ADP-Riboxanate Host Apoptotic Caspases

Programmed cell death is a suicidal defense mechanism for eukaryotes to combat pathogen infection. In the evolutionary arms race with the host, bacteria are endowed with ingenious tactics to block host cell death to facilitate their replication. ABSTRACT Blocking host cell death is an important virulence strategy employed by many bacterial pathogens. We recently reported that Shigella flexneri inhibits host pyroptosis by delivering a type III secretion system (T3SS) effector OspC3 that catalyzes a novel arginine ADP-riboxanation modification on caspase-4/11. Here, we investigated the OspC3 homologue CopC from Chromobacterium violaceum, an opportunistic but sometimes deadly bacterial pathogen. CopC bears the same arginine ADP-riboxanase activity as OspC3, but with a different substrate specificity. Through proteomic analysis, we first identified host calmodulin (CaM) as a binding partner of CopC. The analyses additionally revealed that CopC preferably modifies apoptotic caspases including caspase-7, -8 and -9. This results in suppression of both extrinsic and intrinsic apoptosis programs in C. violaceum-infected cells. Biochemical reconstitution showed that CopC requires binding to CaM, specifically in the calcium-free state, to achieve efficient ADP-riboxanation of the caspases. We determined crystal structure of the CaM-CopC-CASP7 ternary complex, which illustrates the caspase recognition mechanism and a unique CaM-binding mode in CopC. Structure-directed mutagenesis validated the functional significance of CaM binding for stimulating CopC modification of its caspase substrates. CopC adopts an ADP-ribosyltransferase-like fold with a unique His-Phe-Glu catalytic triad, featuring two acidic residues critical for site-specific arginine ADP-riboxanation. Our study expands and deepens our understanding of the OspC family of ADP-riboxanase effectors. IMPORTANCE Programmed cell death is a suicidal defense mechanism for eukaryotes to combat pathogen infection. In the evolutionary arms race with the host, bacteria are endowed with ingenious tactics to block host cell death to facilitate their replication. Here, we report that the C. violaceum effector CopC ADP-riboxanates caspase-7/8/9, enabled by interacting with the host factor calmodulin, to block host cell apoptosis, illustrating a unique and sophisticated strategy adopted by the pathogen to counteract host defense.
Antibody Profiling in COVID-19 Patients with Different Severities by Using Spike Variant Protein Microarrays

The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants. Next, we collected the serums from healthy subjects and COVID-19 patients with different severities and profile the neutralizing activity as well as antibody isotypes. We identified the inhibition of ACE2 binding was stronger against multiple variants in severe compared to mild/moderate or critical patients. Moreover, the serum IgG against nonstructural protein 3 was elevated in severe but not in mild/moderate and critical cases. Finally, we evaluated two ACE2 inhibitors, Ramipril and Perindopril, and found the dose-dependent inhibition of ACE2 binding to all the spike variants except for B.1. 617.3. Together, the SVPM and the assay procedures provide a tool for profiling neutralizing antibodies, antibody isotypes, and reagent specificities.
Improving Multispike Learning With Plastic Synaptic Delays

Emulating the spike-based processing in the brain, spiking neural networks (SNNs) are developed and act as a promising candidate for the new generation of artificial neural networks that aim to produce efficient cognitions as the brain. Due to the complex dynamics and nonlinearity of SNNs, designing efficient learning algorithms has remained a major difficulty, which attracts great research attention. Most existing ones focus on the adjustment of synaptic weights. However, other components, such as synaptic delays, are found to be adaptive and important in modulating neural behavior. How could plasticity on different components cooperate to improve the learning of SNNs remains as an interesting question. Advancing our previous multispike learning, we propose a new joint weight-delay plasticity rule, named TDP-DL, in this article. Plastic delays are integrated into the learning framework, and as a result, the performance of multispike learning is significantly improved. Simulation results highlight the effectiveness and efficiency of our TDP-DL rule compared to baseline ones. Moreover, we reveal the underlying principle of how synaptic weights and delays cooperate with each other through a synthetic task of interval selectivity and show that plastic delays can enhance the selectivity and flexibility of neurons by shifting information across time. Due to this capability, useful information distributed away in the time domain can be effectively integrated for a better accuracy performance, as highlighted in our generalization tasks of the image, speech, and event-based object recognitions. Our work is thus valuable and significant to improve the performance of spike-based neuromorphic computing.
Developing additional herbicide control options for rubber vine (Cryptostegia grandiflora R.BR.)

Herbicide control of rubber vine (Cryptostegia grandiflora R.Br.), a Weed of National Significance in Australia, can be effectively achieved in most situations using a range of chemicals and various techniques, including basal bark, cut stump, foliar and aerial applications. Nevertheless control in areas with poor access and with native vegetation still poses difficulties for some land managers, particularly doing so in a cost effective manner. The successful incorporation of low-volume high-concentration herbicide applications into control programs for several woody weeds in recent years prompted further testing of this technique for control of rubber vine. The efficacy of single rates of four herbicides plus a combination of two herbicides was compared against an untreated control. The herbicide treatments tested contained the active ingredients aminopyralid/ metsulfuron-methyl (375/300 g a.i. kg−1), metsulfuron-methyl (600 g a.i. kg−1), metsulfuronmethyl + glyphosate (600 + 360 g a.i. kg−1), triclopyr/ picloram (300/100 g a.i. kg−1) and triclopyr/picloram/ aminopyralid (200/100/25 g a.i. kg−1). Two years after application, triclopyr/picloram was the only treatment to have given 100% mortality, but statistically it was not significantly different (P >0.05) to aminopyralid/metsulfuron-methyl, metsulfuronmethyl or triclopyr/picloram/aminopyralid, which averaged between 82–91% mortality. The metsulfuronmethyl + glyphosate treatment performed poorly (49% mortality): this appears to be associated with some antagonistic effect given that metsulfuron-methyl on its own performed much better. Based on these results, two more trials have been initiated to refine rates for metsulfuron-methyl and triclopyr/picloram and to compare low-volume high-concentration applications against traditional foliar spraying using the same herbicide (triclopyr/picloram) (in terms of efficacy and cost).
The autophagy-related proteins FvAtg4 and FvAtg8 are involved in virulence and fumonisin biosynthesis in Fusarium verticillioides

ABSTRACT Autophagy is the main intracellular degradation system by which cytoplasmic materials are transported to and degraded in the vacuole/lysosome of eukaryotic cells, and it also controls cellular differentiation and virulence in a variety of filamentous fungi. However, the contribution of the autophagic pathway to fungal development and pathogenicity in the important maize pathogen and mycotoxigenic fungus Fusarium verticillioides is still unknown. In this study, we characterized two autophagy-related proteins, FvAtg4 and FvAtg8. The F. verticillioides deletion mutants ΔFvAtg4 and ΔFvAtg8 were impaired in autophagosome formation, aerial hyphal formation, sexual growth, lipid turnover, pigmentation and fungal virulence. Interestingly, ΔFvAtg4 and ΔFvAtg8 were defective in fumonisin B1 (FB1) synthesis, which may have resulted from decreased intracellular levels of alanine in the mutants. Our results indicate that FvAtg4 and FvAtg8 contribute to F. verticillioides pathogenicity by regulating the autophagic pathway to control lipid turnover, fumonisin biosynthesis, and pigmentation during its infectious cycle.
A review of hepatic fibrosis‐associated histopathology in aged cadavers

This article reviews hepatic fibrosis‐associated histopathology of aged cadavers (mean age 82 years). A study of 68 livers identified steatosis in 35.5%, central vein fibrosis in 49.2%, perisinusoidal fibrosis in 63.2%, portal tract fibrosis in 47.7%, septa formation in 44.1%, bridging fibrosis in 30.8%, and cirrhosis in 4.4% of the samples as well as one hepatocellular carcinoma and six metastatic tumors. Other studies have revealed that collagens I, III, IV, V, and VI and fibronectin constitute the matrices of fibrous central veins, perisinusoidal space, portal tracts, and septa. Elastin is rich in portal tracts and fibrous septa but absent from the perisinusoidal space. Hepatic stellate cells are ubiquitous in the liver parenchyma while myofibroblasts localize in fibrotic foci. Factor VIII‐related antigen expression signals sinusoidal to systemic vascular endothelium transformation while collagen IV and laminin codistribution indicates formation of perisinusoidal membranes. Their coincidence reflects focalized capillarization of sinusoids in the aged liver. In response to fibrogenesis, hepatic progenitor cells residing in the canal of Hering in the periportal parenchyma undergo expansion and migration deep into the lobule. Concomitantly, intermediate hepatocyte‐like cells increase in advanced fibrosis stages, which is possibly related to hepatic regeneration. Metabolic zonation of glutamine synthetase expands from the perivenous to non‐perivenous parenchyma in fibrosis progression but its expression is lost in cirrhosis, while cytochrome P‐4502E1 expression is maintained in centrilobular and midlobular zones in fibrosis progression and expressed in cirrhosis. Hence, cadaveric livers provide a platform for further investigation of hepatic histopathologies associated with the aging liver.
A Campus Big-Data Platform Architecture for Data Mining and Business Intelligence in Education Institutes

Although the commercial business area has witnessed successful applications of BI technologies, in the noncommercial education institute, BI is still in its early adoption phase, partly due to the budget constraint. In addition, the introduction of new Internet-of-Things technologies in campuses brings unprecedented rich data that reflect students' activities in their campus life. The big data provides valuable insight for further improvement of the campus management as well as strategic decision-making of the institutes. On the other hand, it also sets forward challenges on the traditional campus information system. In this paper, we present our big data platform architecture design for the BI application system on the basis of the successful project experience of the university. The architecture has the outstanding advantages in the cost, expandability and scalability. The realized BI analytical functions have played a significant role in the decision making in the university's strategic and routine management.
Mapping the Lay of the Land: Using Interactive Network Analytic Tools for Collaboration in Rural Cancer Prevention and Control

Abstract Background: Cancer mortality rates in the United States are higher in rural than urban areas, especially for colorectal cancer. Modifiable cancer risks (e.g., tobacco use, obesity) are more prevalent among U.S. rural than urban residents. Social network analyses are common, yet rural informal collaborative networks for cancer prevention and control and practitioner uses of network findings are less well understood. Methods: In five service areas in rural Missouri and Illinois, we conducted a network survey of informal multisector networks among agencies that address cancer risk (N = 152 individuals). The survey asked about contact, collaborative activities, and referrals. We calculated descriptive network statistics and disseminated network visualizations with rural agencies through infographics and interactive Network Navigator platforms. We also collected feedback on uses of network findings from agency staff (N = 14). Results: Service areas had more connections (average degree) for exchanging information than for more time-intensive collaborative activities of co-developing and sustaining ongoing services and programs, and co-developing and sharing resources. On average, collaborative activities were not dependent on just a few agencies to bridge gaps to hold networks together. Users found the network images and information useful for identifying gaps, planning which relationships to establish or enhance to strengthen certain collaborative activities and cross-referrals, and showing network strengths to current and potential funders. Conclusions: Rural informal cancer prevention and control networks in this study are highly connected and largely decentralized. Impact: Disseminating network findings help ensure usefulness to rural health and social service practitioners who address cancer risks.