Transformer-based approach to variable typing.

The upsurge of multifarious endeavors across scientific fields propelled Big Data in the scientific domain. Despite the advancements in management systems, researchers find that mathematical knowledge remains one of the most challenging to manage due to the latter's inherent heterogeneity. One novel recourse being explored is variable typing where current works remain preliminary and, thus, provide a wide room for contribution. In this study, a primordial attempt to implement the end-to-end Entity Recognition (ER) and Relation Extraction (RE) approach to variable typing was made using the BERT (Bidirectional Encoder Representations from Transformers) model. A micro-dataset was developed for this process. According to our findings, the ER model and RE model, respectively, have Precision of 0.8142 and 0.4919, Recall of 0.7816 and 0.6030, and F1-Scores of 0.7975 and 0.5418. Despite the limited dataset, the models performed at par with values in the literature. This work also discusses the factors affecting this BERT-based approach, giving rise to suggestions for future implementations.

Descending Control of Nociception Poorly Predicts the Development of Persistent Postsurgical Pain-like Behavior in Consomic Dahl S Rat Strains.

BACKGROUND: Chronic postsurgical pain is a poorly recognized outcome of surgery where patients experience pain long after healing from the surgical insult. Descending control of nociception, a phenomenon whereby application of a strong nociceptive stimulus to one part of the body of animals inhibits pain in remote body regions, offers one strategy to identify a propensity to develop chronic postsurgical pain-like behavior. Here, consomic rat panel was used to test the hypothesis that pain persistence is mechanistically linked to ineffective descending control of nociception. METHODS: Male and female Brown Norway, Dahl S, and eight consomic strains (SS-xBN) were used to determine the presence of chronic postsurgical pain-like behaviors by using paw-withdrawal threshold evaluation (von Frey method) in the area adjacent to a hind paw plantar incision. Descending control of nociception was assessed by measuring hind paw-withdrawal thresholds (Randall-Selitto method) after capsaicin (125 µg) injection into a forepaw. Consomic rats were developed by introgressing individual Brown Norway chromosomes on the Dahl S rat genetic background, as Dahl S rats lack preoperative descending control of nociception. RESULTS: Substitution of several chromosomes from the "pain-resistant" Brown Norway to the "pain-prone" Dahl S/Medical College of Wisconsin reduced mechanical nociceptive sensitivity and increased endogenous pain modulation capacity by differing degrees. Statistical modeling of these data revealed that descending control of nociception is a poor general predictor of the propensity to develop chronic postsurgical pain-like behavior (poor fit for model 1). However, a significant strain-by-descending control of nociception interaction was revealed (model 3, -2*log likelihood; 550.668, -2ll change; 18.093, P = 0.034) with SS-13BN and SS-15BN strains showing a negative descending control of nociception relationship with chronic postsurgical pain-like behavior. CONCLUSIONS: Descending control of nociception poorly predicted which rat strains developed chronic postsurgical pain-like behavior despite controlling for genetic, environmental, and sex differences. Two consomic strains that mimic clinical chronic postsurgical pain criteria and display a strong negative correlation with descending control of nociception were identified, offering novel candidates for future experiments exploring mechanisms that lead to chronic postsurgical pain.

Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain.

Animal models are essential for studying the pathophysiology of chronic pain disorders and as screening tools for new therapies. However, most models available do not reproduce key characteristics of clinical persistent pain. This has limited their ability to accurately predict which new medicines will be clinically effective. Here, we characterize the Dahl salt-sensitive (SS) rat strain as the first rodent model of inherited widespread hyperalgesia. We show that this strain exhibits physiological phenotypes known to contribute to chronic pain, such as neuroinflammation, defective endogenous pain modulation, dysfunctional hypothalamic-pituitary-adrenal axis, increased oxidative stress and immune cell activation. When compared with Sprague Dawley and Brown Norway rats, SS rats have lower nociceptive thresholds due to increased inflammatory mediator concentrations, lower corticosterone levels, and high oxidative stress. Treatment with dexamethasone, the reactive oxygen species scavenger tempol, or the glial inhibitor minocycline attenuated the pain sensitivity in SS rats without affecting the other strains while indomethacin and gabapentin provided less robust pain relief. Moreover, SS rats presented impaired diffuse noxious inhibitory controls and an exacerbated response to the proalgesic mediator PGE2, features of generalized pain conditions. These data establish this strain as a novel model of spontaneous, widespread hyperalgesia that can be used to identify biomarkers for chronic pain diagnosis and treatment.

Excitation of Putative Glutamatergic Neurons in the Rat Parabrachial Nucleus Region Reduces Delta Power during Dexmedetomidine but not Ketamine Anesthesia.

BACKGROUND: Parabrachial nucleus excitation reduces cortical delta oscillation (0.5 to 4 Hz) power and recovery time associated with anesthetics that enhance γ-aminobutyric acid type A receptor action. The effects of parabrachial nucleus excitation on anesthetics with other molecular targets, such as dexmedetomidine and ketamine, remain unknown. The hypothesis was that parabrachial nucleus excitation would cause arousal during dexmedetomidine and ketamine anesthesia. METHODS: Designer Receptors Exclusively Activated by Designer Drugs were used to excite calcium/calmodulin-dependent protein kinase 2α-positive neurons in the parabrachial nucleus region of adult male rats without anesthesia (nine rats), with dexmedetomidine (low dose: 0.3 µg · kg-1 · min-1 for 45 min, eight rats; high dose: 4.5 µg · kg-1 · min-1 for 10 min, seven rats), or with ketamine (low dose: 2 mg · kg-1 · min-1 for 30 min, seven rats; high dose: 4 mg · kg-1 · min-1 for 15 min, eight rats). For control experiments (same rats and treatments), the Designer Receptors Exclusively Activated by Designer Drugs were not excited. The electroencephalogram and anesthesia recovery times were recorded and analyzed. RESULTS: Parabrachial nucleus excitation reduced delta power in the prefrontal electroencephalogram with low-dose dexmedetomidine for the 150-min analyzed period, excepting two brief periods (peak median bootstrapped difference [clozapine-N-oxide - saline] during dexmedetomidine infusion = -6.06 [99% CI = -12.36 to -1.48] dB, P = 0.007). However, parabrachial nucleus excitation was less effective at reducing delta power with high-dose dexmedetomidine and low- and high-dose ketamine (peak median bootstrapped differences during high-dose [dexmedetomidine, ketamine] infusions = [-1.93, -0.87] dB, 99% CI = [-4.16 to -0.56, -1.62 to -0.18] dB, P = [0.006, 0.019]; low-dose ketamine had no statistically significant decreases during the infusion). Recovery time differences with parabrachial nucleus excitation were not statistically significant for dexmedetomidine (median difference for [low, high] dose = [1.63, 11.01] min, 95% CI = [-20.06 to 14.14, -20.84 to 23.67] min, P = [0.945, 0.297]) nor low-dose ketamine (median difference = 12.82 [95% CI: -3.20 to 39.58] min, P = 0.109) but were significantly longer for high-dose ketamine (median difference = 11.38 [95% CI: 1.81 to 24.67] min, P = 0.016). CONCLUSIONS: These results suggest that the effectiveness of parabrachial nucleus excitation to change the neurophysiologic and behavioral effects of anesthesia depends on the anesthetic's molecular target.

D2 Receptors in the Periaqueductal Gray/Dorsal Raphe Modulate Peripheral Inflammatory Hyperalgesia via the Rostral Ventral Medulla.

Dopamine neurons in the periaqueductal gray (PAG)/dorsal raphe are key modulators of antinociception with known supraspinal targets. However, no study has directly tested whether these neurons contribute to descending pain inhibition. We hypothesized that PAG dopamine neurons contribute to the analgesic effect of D-amphetamine via a mechanism that involves descending modulation via the rostral ventral medulla (RVM). Male C57BL/6 mice showed increased c-FOS expression in PAG dopamine neurons and a significant increase in paw withdrawal latency to thermal stimulation after receiving a systemic injection of D-amphetamine. Targeted microinfusion of D-amphetamine, L-DOPA, or the selective D2 agonist quinpirole into the PAG produced analgesia, while a D1 agonist, chloro APB, had no effect. In addition, inhibition of D2 receptors in the PAG by eticlopride prevented the systemic D-amphetamine analgesic effect. D-amphetamine and PAG D2 receptor-mediated analgesia were inhibited by intra-RVM injection of lidocaine or the GABAA receptor agonist muscimol, indicating a PAG-RVM signaling pathway in this model of analgesia. Finally, both systemic D-amphetamine and local PAG microinjection of quinpirole, inhibited inflammatory hyperalgesia induced by carrageenan. This hyperalgesia was transiently restored by intra-PAG injection of eticlopride, as well as RVM microinjection of muscimol. We conclude that D-amphetamine analgesia is partially mediated by descending inhibition and that D2 receptors in the PAG are responsible for this effect via modulating neurons that project to the RVM. These results further our understanding of the antinociceptive effects of dopamine and elucidate a mechanism by which clinically available dopamine modulators produce analgesia.

Acoustic levitation: recent developments and emerging opportunities in biomaterials research.

Containerless sample environments (levitation) are useful for study of nucleation, supercooling, and vitrification and for synthesis of new materials, often with non-equilibrium structures. Elimination of extrinsic nucleation by container walls extends access to supercooled and supersaturated liquids under high-purity conditions. Acoustic levitation is well suited to the study of liquids including aqueous solutions, organics, soft materials, polymers, and pharmaceuticals at around room temperature. This article briefly reviews recent developments and applications of acoustic levitation in materials R&D. Examples of experiments yielding amorphous pharmaceutical materials are presented. The implementation and results of experiments on supercooled and supersaturated liquids using an acoustic levitator at a high-energy X-ray beamline are described.