Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of topical and systemic administration of Eugenia caryophyllata buds essential oil on corneal anesthesia and analgesia

Clinical studies suggest that essential oil of Eugenia caryophyllata (Clove) buds (EOEC) is efficacious in the treatment of dental pain. In the present study, we investigated the analgesic and local anesthetic effects of EOEC and its possible mechanisms of action in acute corneal pain in rats. EOEC was extracted by hydro-distillation in a Clevenger type apparatus from clove buds. The acute corneal pain was induced by applying a drop (40 µl) of 5 M NaCl solution on the corneal surface, and the numbers of eye wipes were counted during the first 30 s. The mechanical sensation of the cornea was evaluated by calibrated Von Frey filaments. Systemic administration of EOEC (100 and 200 mg/kg, SC) and morphine (2.5 and 5 mg/kg, IP) produced a significant antinociceptive effect in acute corneal pain. Pretreatment with naloxone or atropine prevented the EOEC-induced analgesia. However, L-arginine and methylene blue did not change the suppressive effect of EOEC on corneal pain response. Topical application of EOEC, eugenol and lidocaine significantly decreased corneal sensitivity. Combination treatments of eugenol (25 µg) with lidocaine (0.5%) and EOEC (50 µg) with lidocaine (0.5%) also significantly suppressed corneal sensitivity. Systemic administration of EOEC produced analgesia in the acute corneal pain through mechanisms that involved both opioidergic and cholinergic systems. In addition, topical instillation of EOEC, eugenol, and lidocaine produced local anesthesia in the rat cornea. Sub-anesthetic doses of EOEC or eugenol produced a significant local anesthetic effect when concurrently used with the sub-anesthetic dose of lidocaine.
Comparative Anticonvulsant and Mechanistic Profile of the Established and Newer Antiepileptic Drugs

Since 1993, several new antiepileptic drugs (AEDs) have been introduced for management of partial seizures. Like the established AEDs, the new drugs are believed to exert their anticonvulsant action through enhancement of inhibitory‐mediated neurotransmission, or reduction of excitatory‐mediated neurotransmission, or by a combination of both. Among the new drugs, vigabatrin (VGB) and tiagabine (TGB) are unique in that they were derived from mechanistic‐based drug discovery programs designed to identify effective AEDs that inhibit the metabolism and reuptake of the inhibitory neurotransmitter GABA, respectively. For many of the newer AEDs, several molecular mechanisms of action have been identified. For example, felbamate (FBM), lamotrigine (LTG), zonisamide (ZNS), topiramate (TPM), oxcarbazepine (OCBZ), and possibly gabapentin (GBP) share a similar mechanism with that defined for phenytoin (PHT) and carbamazepine (CBZ), i.e., a voltage‐ and use‐dependent block of voltage‐sensitive sodium (Na+) channels. In addition to their effects on Na+ currents, TPM, ZNS, and FBM also appear to act as allosteric modulators of the GABAA receptor, whereas GBP appears to increase brain GABA levels. GBP, ZNS, FBM, LTG, and OCBZ attenuate voltage‐sensitive calcium (Ca2+) channels, albeit through different mechanisms and with different classes of Ca2+ channels. FBM and TPM differ from both the established and newer AEDs in their ability to modulate NMDA‐ and AMPA/kainate‐mediated excitatory neurotransmission, respectively. The multiple mechanisms of action associated with FBM, TPM, ZNS, GBP, and perhaps LTG, and the unique modulation of GABA levels by VGB and TGB, are likely to account for the anticonvulsant efficacy of these newer AEDs in patients with epilepsy. For each of the new drugs, their proposed mechanisms of action are discussed in relationship to their preclinical and clinical anticonvulsant profiles.
Explorer Recognizing emotions in dialogue with disfluences and non-verbal vocalisations

We investigate the usefulness of DISfluencies and Non-verbal Vocalisations (DIS-NV) for recognizing human emotions in dialogues. The proposed features measure filled pauses, fillers, stutters, laughter, and breath in utterances. The predictiveness of DISNV features is compared with lexical features and state-of-the-art low-level acoustic features. Our experimental results show that using DIS-NV features alone is not as predictive as using lexical or acoustic features. However, adding them to lexical or acoustic feature set yields improvement compared to using lexical or acoustic features alone. This indicates that disfluencies and non-verbal vocalisations provide useful information overlooked by the other two types of features for emotion recognition.
From Colombo to Athens : Areal and Universalist Perspectives on Bilingual Compound Verbs

Most or all bilingual varieties of the languages spoken in the area between Sri Lanka and Greece have bilingual compound verbs, consisting of a lexical content verb from a donor language and a helping verb from the matrix language. In this paper, these verbs are described and analyzed, and the question is raised whether this widespread occurrence is specifically an areal feature, or a universally available pattern and a question of typological poise—the possibility of a construction arising due to propitious typological circumstances. Pleading for the areal perspective, it is concluded there is the fact that two large and important language families—Turkic and Indo-Iranian—either rapidly developed or already had a productive [noun + verb] construction. On the universalist side, it is clear that native [noun + verb] constructions very easily develop into [verb + verb] constructions in bilingual settings, though not in monolingual settings. This is a cross-generational change that is a contact phenomenon; that is to say, this development does not occur in monolingual, non-contact language settings.
Health savings accounts and health care spending.

OBJECTIVE The impact of consumer-driven health plans (CDHPs) has primarily been studied in a small number of large, self-insured employers, but this work may not generalize to the wide array of firms that make up the overall economy. The goal of our research is to examine effects of health savings accounts (HSAs) on total, medical, and pharmacy spending for a large number of small and midsized firms. DATA SOURCES Health plan administrative data from a national insurer were used to measure spending for 76,310 enrollees over 3 years in 709 employers. All employers began offering a HSA-eligible plan either on a full-replacement basis or alongside traditional plans in 2006 and 2007 after previously offering only traditional plans in 2005. STUDY DESIGN We employ difference-in-differences generalized linear regression models to examine the impact of switching to HSAs. DATA EXTRACTION METHODS; Claims data were aggregated to enrollee-years. PRINCIPAL FINDINGS For total spending, HSA enrollees spent roughly 5-7 percent less than non-HSA enrollees. For pharmacy spending, HSA enrollees spent 6-9 percent less than traditional plan enrollees. More of the spending decrease was observed in the first year of enrollment. CONCLUSIONS Our findings are consistent with the notion that CDHP benefit designs affect decisions that are at the discretion of the consumer, such as whether to fill or refill a prescription, but have less effect on care decisions that are more at the discretion of the provider.
Nucleosynthesis, Reionization, and the Mass Function of the First Stars

We critique the hypothesis that the first stars were very massive stars (VMSs; M > 140 M☉). We review the two major lines of evidence for the existence of VMSs: (1) that the relative metal abundances of extremely metal-poor Galactic halo stars show evidence of VMS enrichment and (2) that the high electron-scattering optical depth (τe) to the cosmic microwave background found by the Wilkinson Microwave Anisotropy Probe (WMAP) requires VMSs for reionization in a concordance ΛCDM cosmology. The yield patterns of VMSs exploding as pair-instability supernovae are incompatible with the Fe-peak and r-process abundances in halo stars. Models including Type II supernovae and/or "hypernovae" from zero-metallicity progenitors with M = 8-40 M☉ can better explain the observed trends. We use the nucleosynthesis results and stellar evolution models to construct an initial mass function (IMF) for reionization. With a simple metal transport model, we estimate that halo enrichment curtails metal-free star formation after ~108 yr at z ~ 20. Because the lifetime-integrated ionizing photon efficiency of metal-free stars peaks at ~120 M☉ and declines at higher mass, an IMF with an approximate lower bound at M ~ 10-20 M☉ and no VMS can maximize the ionizing photon budget and still be consistent with the nucleosynthetic evidence. An IMF devoid of low-mass stars is justified independently by models of the formation of primordial stars. Using a semianalytic model for H I and He II reionization, we find that such an IMF can reproduce τe ≃ 0.10-0.14, consistent with the range from WMAP, without extreme astrophysical assumptions, provided that metal-free star formation persists 107-108 yr after star formation begins. Because stars in the mass range 50-140 M☉ are the most efficient sources of ionizing photons but are expected to collapse to black holes without releasing metals, this IMF effectively decouples early metal enrichment and early ionization. Such an IMF may allow the unique properties of the zero-metallicity IMF to persist longer than they would in the pure VMS case and to contribute significantly to the global ionizing photon budget before halo self-enrichment and/or interhalo metal transport truncates metal-free star formation. We conclude, on the basis of these results, that VMSs are not necessary to meet the existing constraints commonly taken to motivate them.
Willow: A User-Programmable SSD

We explore the potential of making programmability a central feature of the SSD interface. Our prototype system, called Willow, allows programmers to augment and extend the semantics of an SSD with application-specific features without compromising file system protections. The SSD Apps running on Willow give applications low-latency, high-bandwidth access to the SSD's contents while reducing the load that IO processing places on the host processor. The programming model for SSD Apps provides great flexibility, supports the concurrent execution of multiple SSD Apps in Willow, and supports the execution of trusted code in Willow. We demonstrate the effectiveness and flexibility of Willow by implementing six SSD Apps and measuring their performance. We find that defining SSD semantics in software is easy and beneficial, and that Willow makes it feasible for a wide range of IO-intensive applications to benefit from a customized SSD interface.
Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir

Objective:Atazanavir (ATV) and lopinavir (LPV) have been associated with kidney disease progression in HIV positive patients, with no data reported for darunavir (DRV). We examined kidney function in patients who switched their protease inhibitor from ATV or LPV to DRV. Design:Cohort study. Methods:Data were from the UK CHIC study. We compared pre and post switch estimated glomerular filtration rate (eGFR) slopes (expressed in ml/min per 1.73 m2 per year) in all switchers and those with rapid eGFR decline (>5 ml/min per 1.73 m2 per year) on ATV or LPV. Mixed-effects models were adjusted for age, gender, ethnicity, eGFR at switch and time updated CD4+ cell count, HIV RNA and cumulative tenofovir (tenofovir disoproxil fumarate) exposure. Results:Data from 1430 patients were included. At the time of switching to DRV, median age was 45 years, 79% were men, 76% had an undetectable viral load, and median eGFR was 93 ml/min per 1.73 m2. Adjusted mean (95% confidence interval) pre and post switch eGFR slopes were −0.84 (−1.31, −0.36) and 1.23 (0.80, 1.66) for ATV (P < 0.001), and −0.57 (−1.09, −0.05) and 0.62 (0.28, 0.96) for LPV (P < 0.001). Stable or improved renal function was observed in patients with rapid eGFR decline on ATV or LPV who switched to DRV [−15.27 (−19.35, −11.19) and 3.72 (1.78, 5.66), P < 0.001 for ATV, −11.93 (−14.60, −9.26) and 0.87 (−0.54, 2.27), P < 0.001 for LPV]. Similar results were obtained if participants who discontinued tenofovir disoproxil fumarate at the time of switch were excluded. Conclusions:We report improved kidney function in patients who switched from ATV or LPV to DRV, suggesting that DRV may have a more favourable renal safety profile.
Biological Evidence That SOCS-2 Can Act Either as an Enhancer or Suppressor of Growth Hormone Signaling*

Suppressor of cytokine signaling (SOCS)-2 is a member of a family of intracellular proteins implicated in the negative regulation of cytokine signaling. The generation of SOCS-2-deficient mice, which grow to one and a half times the size of their wild-type littermates, suggests that SOCS-2 may attenuate growth hormone (GH) signaling. In vitro studies indicate that, while SOCS-2 can inhibit GH action at low concentrations, at higher concentrations it may potentiate signaling. To determine whether a similar enhancement of signaling is observed in vivo or alternatively whether increased SOCS-2 levels repress growth in vivo, we generated and analyzed transgenic mice that overexpress SOCS-2 from a human ubiquitin C promoter. These mice are not growth-deficient and are, in fact, significantly larger than wild-type mice. The overexpressed SOCS-2 was found to bind to endogenous GH receptors in a number of mouse organs, while phosphopeptide binding studies with recombinant SOCS-2 defined phosphorylated tyrosine 595 on the GH receptor as the site of interaction. Together, the data implicate SOCS-2 as having dual effects on GH signaling in vivo.
Impact of Acetazolamide and CPAP on Cortical Activity in Obstructive Sleep Apnea Patients

Study Objectives 1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy. Design Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed. Setting Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m. Patients Study 1: 39 OSAS patients. Study 2: 41 OSAS patients. Interventions Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500–750 mg) or placebo at moderate altitudes. Measurements and Results An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5–10%) and increase in beta activity (approximately 25%). Conclusions The higher evening dose of 500 mg acetazolamide showed the “spectral fingerprint” of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.
Evidence for Involvement of Th17 Type Responses in Post Kala Azar Dermal Leishmaniasis (PKDL)

Background Post kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis, caused by Leishmania donovani, constitutes an important reservoir for the parasite. Parallel functioning of counter acting immune responses (Th1/Th2) reflects a complex immunological scenario, suggesting the involvement of additional regulatory molecules in the disease pathogenesis. Methodology/Principal Findings In the present study, human cytokine/chemokine/receptor specific cDNA array technique was employed to identify modulations in gene expression of host immuno-determinants during PKDL, followed by evaluation of Th17 type responses by analyzing mRNA and protein expression of Th17 markers (IL-23, IL-17, RORγt) and performing functional assays using Leishmania antigen (TSLA) or recombinant (rec)IL-17. Array analysis identified key immuno-regulatory molecules including cytokines (TNF-α, IFN-γ, IL-10, IL-17), chemokines (MCP-1, MIP-1α), apoptotic molecules (FasL, TRAIL, IRF-1) and receptors (CD40, Fas). Up regulation in lesional expression of Th17 markers was observed during PKDL compared to control (IL-17 and IL-23, P = 0.0008; RORγt, P = 0.02). In follow-up samples, chemotherapy significantly down regulated expression of all markers. In addition, lesional expression of IL-17 was confirmed at protein level by Immuno-histochemistry. Further, systemic presence of Th17 responses (IL-17 and IL-23) was observed in plasma samples from PKDL patients. In functional assays, TSLA stimulated the secretion of IL-17 and IL-23 from PBMCs of PKDL patients, while recIL-17 enhanced the production of TNF-α as well as nitric oxide (NO) in PKDL compared to control (TNF-α, P = 0.0002; NO, P = 0.0013). Further, a positive correlation was evident between lesional mRNA expression of IL-17 and TNF-α during PKDL. Conclusion/Significance The results highlight key immune modulators in PKDL and provide evidence for the involvement of Th17 type responses in the disease pathogenesis.
Transfer of a Catabolic Pathway for Chloromethane in Methylobacterium Strains Highlights Different Limitations for Growth with Chloromethane or with Dichloromethane

Chloromethane (CM) is an ozone-depleting gas, produced predominantly from natural sources, that provides an important carbon source for microbes capable of consuming it. CM catabolism has been difficult to study owing to the challenging genetics of its native microbial hosts. Since the pathways for CM catabolism show evidence of horizontal gene transfer, we reproduced this transfer process in the laboratory to generate new CM-catabolizing strains in tractable hosts. We demonstrate that six putative accessory genes improve CM catabolism, though heterologous expression of only one of the six is strictly necessary for growth on CM. In contrast to growth of Methylobacterium strains with the closely related compound dichloromethane (DCM), we find that chloride export does not limit growth on CM and, in general that the ability of a strain to grow on DCM is uncorrelated with its ability to grow on CM. This heterologous expression system allows us to investigate the components required for effective CM catabolism and the factors that limit effective catabolism after horizontal transfer.
Current Knowledge on Phylogeny and Taxonomy of Rickettsia spp.

Due to improved diagnostic methods and increased interest, the number of representatives of the genus Rickettsia has increased dramatically over the past 20 years, with 25 currently validated species. These arthropod‐associated intracellular bacteria are now recognized in all parts of the world. The comparison of the phylogenic organizations obtained from the study of several genes with different functions, and more recently from genomic sequences, provided basis to establish a reliable taxonomy of the bacteria induded in the genus Rickettsia. These data were incorporated into polyphasic consensus guidelines that provide clear recommendations for the taxonomic classification and nomenclature of rickettsiae and rickettsial diseases.
Association of 3 Common Polymorphisms of IL-27 Gene with Susceptibility to Cancer in Chinese: Evidence From an Updated Meta-Analysis of 27 Studies

Background Many epidemiology studies have indicated that several functional polymorphisms of the IL-27 gene may contribute to individual susceptibility to cancer. Nevertheless, the data arising from these studies were inconclusive. Therefore, we conducted the current meta-analysis aiming to elucidate the effects of IL-27 polymorphisms (rs153109, rs17855750, and rs181206) on cancer susceptibility. Material/Methods We searched the CNKI (Chinese National Knowledge Infrastructure), Wanfang database, PubMed, Web of Science, and Google Scholar for all eligible publications. We used odds ratios (ORs) corresponding with 95% confidence intervals (CIs) by using the random/fixed-effects model to evaluate the association. Finally, a total of 12 publications, including 27 case-control studies comprising of 7570 patients and 9839 controls, were enrolled in our meta-analysis. Results Our work demonstrates that IL-27 rs17855750 polymorphism is significantly associated with cancer susceptibility, particularly for bladder cancer. However, no association between IL-27 rs153109 and rs181206 polymorphisms and cancer susceptibility was identified. When a stratification analysis was performed by cancer type, we identified an increased susceptibility of bladder cancer in rs153109 polymorphism. Moreover, in the stratification analysis by genotyping method, we identified an increased susceptibility for PCR-RFLP group in rs17855750 polymorphism, whereas a decreased susceptibility was identified in rs153109 polymorphism. Conclusions Our study shows that IL-27 rs17855750 polymorphism is significantly associated with increased susceptibility to cancer in Chinese.
A New Generation of Drugs: Synthetic Peptides Based on Natural Regulatory Peptides

Natural regulatory peptides are biologically active compounds that are produced by various cells and provide a link among the main regulatory systems of the body. The field of research into the biologic activity of endogenous regulatory peptides is extremely vast. These peptides affect the cardiovascular, immune, reproductive, endocrine, digestive, and other systems, alter energy metabolism, and are especially effective in the regulation of the central nervous system. Despite of the wide range of preventive and therapeutic effects of natural regulatory peptides and proteins, their application in clinical practice is difficult. This is primarily because of their extreme instability, as they are rapidly degraded by proteases of the gastrointestinal tract, blood, cerebrospinal fluid, and other biologic media. Compounds with higher stability (i.e., a considerably longer half-life compared with that of natural molecules) and the ability to provide a directional effect on the various body systems were obtained from modifications of endogenous regulatory peptides. Synthetic analogs of regulatory peptides, as a rule, contain only natural amino acids in their composition, and their biodegradation does not lead to the formation of toxic products; thus, they have fewer side effects. This review focuses on the consideration of two synthetic regulatory peptides, Semax and Selank, which were the bases for the creation of new drugs that are used effectively in the treatment of various diseases of the nervous system. The synthetic analog of an adrenocorticotropic hormone 4-10 fragment (ACTH4-10) Semax is a powerful neuroprotective agent that is particularly effective as a therapy for stroke. Selank was synthesized on the basis of the natural immunomodulator tuftsin. Selank is a powerful anxiolytic that is used as a therapy for generalized anxiety disorder and neurasthenia without sedative and muscle-relaxant effects. This review presents the results of research aimed at studying the influence of these peptides on the transcriptome of brain cells. The problems of drugs developed based on the clinical activities of Semax and Selank are discussed separately.