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Endometriosis is a chronic and debilitating condition affecting ~10% of women. Endometriosis is characterized by infertility and chronic pelvic pain, yet treatment options remain limited. In many respects this is related to an underlying lack of knowledge of the aetiology and mechanisms contributing to endometriosis-induced pain. Whilst many studies focus on retrograde menstruation, and the formation and development of lesions in the pathogenesis of endometriosis, the mechanisms underlying the associated pain remain poorly described. Here we review the recent clinical and experimental evidence of the mechanisms contributing to chronic pain in endometriosis. This includes the roles of inflammation, neurogenic inflammation, neuroangiogenesis, peripheral sensitization and central sensitization. As endometriosis patients are also known to have co-morbidities such as irritable bowel syndrome and overactive bladder syndrome, we highlight how common nerve pathways innervating the colon, bladder and female reproductive tract can contribute to co-morbidity via cross-organ sensitization.

Once activated at the surface of cells, G protein-coupled receptors (GPCRs) redistribute to endosomes, where they can continue to signal. Whether GPCRs in endosomes generate signals that contribute to human disease is unknown. We evaluated endosomal signaling of protease-activated receptor-2 (PAR₂), which has been proposed to mediate pain in patients with irritable bowel syndrome (IBS). Trypsin, elastase, and cathepsin S, which are activated in the colonic mucosa of patients with IBS and in experimental animals with colitis, caused persistent PAR₂-dependent hyperexcitability of nociceptors, sensitization of colonic afferent neurons to mechanical stimuli, and somatic mechanical allodynia. Inhibitors of clathrin- and dynamin-dependent endocytosis and of mitogen-activated protein kinase kinase-1 prevented trypsin-induced hyperexcitability, sensitization, and allodynia. However, they did not affect elastase- or cathepsin S-induced hyperexcitability, sensitization, or allodynia. Trypsin stimulated endocytosis of PAR₂, which signaled from endosomes to activate extracellular signal-regulated kinase. Elastase and cathepsin S did not stimulate endocytosis of PAR₂, which signaled from the plasma membrane to activate adenylyl cyclase. Biopsies of colonic mucosa from IBS patients released proteases that induced persistent PAR₂-dependent hyperexcitability of nociceptors, and PAR₂ association with β-arrestins, which mediate endocytosis. Conjugation to cholestanol promoted delivery and retention of antagonists in endosomes containing PAR₂. A cholestanol-conjugated PAR₂ antagonist prevented persistent trypsin- and IBS protease-induced hyperexcitability of nociceptors. The results reveal that PAR₂ signaling from endosomes underlies the persistent hyperexcitability of nociceptors that mediates chronic pain of IBS. Endosomally targeted PAR₂ antagonists are potential therapies for IBS pain. GPCRs in endosomes transmit signals that contribute to human diseases.

This project aimed to develop a mobile app tool to teach the Hiligaynon language to elementary pupils, designed with Machine Learning features using the Hiligaynon-Filipino-English Translation RNN Model. The app included games as a pedagogical tool, background music, and incentives to engage learners. The RNN model was developed using Data Science Methodology, while Rapid Agile Development Methodology was used to develop the mobile app for Android operating systems. To assess the app’s effectiveness, elementary teachers and IT professionals evaluated its compliance with standards for acceptability. The app was found to be very acceptable, recommended for use in a gamified classroom setting and by parents. Overall, this project promotes technology in language learning to make it more accessible and enjoyable for elementary pupils.

The mechanisms underlying chronic bladder conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder syndrome (OAB) are incompletely understood. However, targeting specific receptors mediating neuronal sensitivity to specific stimuli is an emerging treatment strategy. Recently, irritant-sensing receptors including the bile acid receptor TGR5, have been identified within the viscera and are thought to play a key role in neuronal hypersensitivity. Here, in mice, we identify mRNA expression of TGR5 ( Gpbar1 ) in all layers of the bladder as well as in the lumbosacral dorsal root ganglia (DRG) and in isolated bladder-innervating DRG neurons. In bladder-innervating DRG neurons Gpbar1 mRNA was 100% co-expressed with Trpv1 and 30% co-expressed with Trpa1 . In vitro live-cell calcium imaging of bladder-innervating DRG neurons showed direct activation of a sub-population of bladder-innervating DRG neurons with the synthetic TGR5 agonist CCDC, which was diminished in Trpv1 −/− but not Trpa1 −/− DRG neurons. CCDC also activated a small percentage of non-neuronal cells. Using an ex vivo mouse bladder afferent recording preparation we show intravesical application of endogenous (5α-pregnan-3β-ol-20-one sulphate, Pg5α) and synthetic (CCDC) TGR5 agonists enhanced afferent mechanosensitivity to bladder distension. Correspondingly, in vivo intravesical administration of CCDC increased the number of spinal dorsal horn neurons that were activated by bladder distension. The enhanced mechanosensitivity induced by CCDC ex vivo and in vivo was absent using Gpbar1 −/− mice. Together, these results indicate a role for the TGR5 receptor in mediating bladder afferent hypersensitivity to distension and thus may be important to the symptoms associated with IC/BPS and OAB.

The aqua-agriculture food sector, challenged by climate change, exploited biodiversity, food insecurity, water crisis, and global pandemic, urgently needs the sustainability transition and more sustainable practices. Sustainability transitions aim to transform current patterns of production and consumption into sustainable ones while enhancing the ecological and economic situation. This agenda is much possible with the integration of IIoT and AI/ML into the aqua agriculture. In this study, the researchers integrated a Prediction Model based on Bagging and Boosting Ensemble Technique in the Decision Support System of an Autonomous Smart IIoT Smart Aquaponic System that autonomously monitored, controlled, and managed the aquaponic systems.

The Transneptunian Automated Occultation Survey (TAOS II) is a blind occultation survey with the aim of measuring the size distribution of Trans-Neptunian Objects with diameters in the range of 0.3 D 30 km. TAOS II will observe as many as 10,000 stars at a cadence of 20 Hz with all three telescopes simultaneously. This will produce up to ∼20 billion photometric measurements per night, and as many as ∼6 trillion measurements per year, corresponding to over 70 million individual light curves. A very fast analysis pipeline for event detection and characterization is needed to handle this massive data set. The pipeline should be capable of real-time detection of events (within 24 hours of observations) for follow-up observations of any occultations by larger TNOs. In addition, the pipeline should be fast and scalable for large simulations where simulated events are added to the observed light curves to measure detection efficiency and biases in event characterization. Finally, the pipeline should provide estimates of the size of and distance to any occulting objects, including those with non-spherical shapes. This paper describes a new data analysis pipeline for the detection and characterization of occultation events.

Anterior segment optical coherence tomography (AS-OCT) is a non-invasive imaging modality used to evaluate anterior segment features. This report aims to inform clinicians of best practices to obtain high-resolution AS-OCT images of anterior segment features of eyes implanted with the Port Delivery Platform (PDP). In PDP trials, AS-OCT imaging of the anterior segment was performed using Heidelberg Spectralis OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) equipped with the Anterior Segment Module. Images from over 2500 separate study visits were obtained using standardized imaging parameters. The following stepwise approach was recommended to properly orient the volume scans over the extrascleral flange of the PDP ensuring that the scans are centered on the implant with adequate depth: (1) the volume scan was aligned such that: (i) the long axis of the scan was oriented parallel to the implant flange long axis, (ii) the imaging field was centered on the implant septum center, and (iii) it covered the entirety of the implant, with equal margins on either side of the implant flange; (2) the depth of the scan focus was adjusted to ensure that the conjunctiva and Tenon's capsule over the overmold, as well as sclera under the implant flange, and the septum of the implant, were captured; and (3) Steps 1 and 2 were then repeated after the scan orientation was changed so that the short-axis scans were oriented parallel to the implant flange short axis. Utilization of AS-OCT during clinical development of the PDP allowed visualization of anterior segment features, including the conjunctiva, Tenon's capsule, and sclera, surrounding the PDP. Overall, these best practices enabled detailed structural imaging of the implant's interface with surrounding ocular tissues. Common errors resulting in poor AS-OCT image acquisition included off-center raster scans, scans not being aligned parallel to the long and/or short axes of the PDP implant, or not being oriented along the implant axes, and inappropriate scan depths. Application of a standardized AS-OCT imaging procedure was used to obtain high-quality, high-resolution images of anterior segment features in the presence of the PDP implant. The best practices reported are not a requirement for managing eyes with the PDP, but a recommendation for how to obtain high-quality images of the anterior segment of eyes with the PDP implant.

Cardiac electrophysiological simulations are computationally intensive tasks. The growing complexity of cardiac models, together with the increasing use of large ensembles of models (known as populations of models), make extensive simulation studies unfeasible for regular stand-alone computers. To address this problem, we developed DENIS, a cardiac electrophysiology simulator based on the volunteer computing paradigm. We evaluated the performance of DENIS by testing the effect of simulation length, task deadline, and batch size, on the time to complete a batch of simulations. In the experiments, the time to complete a batch of simulations did not increase with simulation length, and had little dependence on batch size. In a test case involving the generation of a population of models, DENIS was able to reduce the simulation time from years to a few days when compared to a stand-alone computer. Such capacity makes it possible to undertake large cardiac simulation projects without the need for high performance computing infrastructure.

Simultaneous activation of multiphotonic absorption and nonlinear optical refraction were employed for developing a multipath load balancing technique assisted by light and zinc oxide nanostructures. Data storage as the real and imaginary part of the third-order nonlinear optical behavior of different regions in bidimensional systems was proposed. By recording the third-order nonlinear optical response exhibited by the nanomaterials, a straightforward XOR encryption system controlled by laser pulses was developed. Identification of nonlinear optical signals in propagation through the samples was monitored by a standard optical Kerr gate configuration. Vectorial two-wave mixing experiments were carried out for measuring the third-order optical nonlinearities of the samples explored by nanosecond pulses at 532 nm wavelength. A spray pyrolysis processing route was employed for the preparation of the samples in thin film form. Third-order nonlinear optical characteristics were analyzed taking into account the modification in the ZnO-based nanocomposites by single-pulsed irradiation close to the ablation threshold effect. The combination of nonlinear optics and nanostructured films can be considered for developing ultrafast smart objects with immediate applications for signal processing functions driven by multiphotonic phenomena.

Improved understanding of vestibulodynia pathophysiology is required to develop appropriately targeted treatments. Established features include vulvovaginal hyperinnervation, increased nociceptive signalling and hypersensitivity. Emerging evidence indicates macrophage-neuron signalling contributes to chronic pain pathophysiology. Macrophages are broadly classified as M1 or M2, demonstrating pro-nociceptive or anti-nociceptive effects respectively. This study investigates the impact of clodronate liposomes, a macrophage depleting agent, on nociceptive signalling in a mouse model of vestibulodynia. Microinjection of complete Freund's adjuvant (CFA) at the vaginal introitus induced mild chronic inflammation in C57Bl/6J mice. A subgroup was treated with the macrophage depleting agent clodronate. Control mice received saline. After 7 days, immunolabelling for PGP9.5, F4/80+CD11c+ and F4/80+CD206+ was used to compare innervation density and presence of M1 and M2 macrophages respectively in experimental groups. Nociceptive signalling evoked by vaginal distension was assessed using immunolabelling for phosphorylated MAP extracellular signal-related kinase (pERK) in spinal cord sections. Hyperalgesia was assessed by visceromotor response to graded vaginal distension. CFA led to increased vaginal innervation (p < 0.05), increased pERK-immunoreactive spinal cord dorsal horn neurons evoked by vaginal-distension (p < 0.01) and enhanced visceromotor responses compared control mice (p < 0.01). Clodronate did not reduce vaginal hyperinnervation but significantly reduced the abundance of M1 and M2 vaginal macrophages and restored vaginal nociceptive signalling and vaginal sensitivity to that of healthy control animals. We have developed a robust mouse model of vestibulodynia that demonstrates vaginal hyperinnervation, enhanced nociceptive signalling, hyperalgesia and allodynia. Macrophages contribute to hypersensitivity in this model. Macrophage-sensory neuron signalling pathways may present useful pathophysiological targets.