Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of opioid receptor gene variation on targeted nalmefene treatment in heavy drinkers.

BACKGROUND Recent studies examining the moderating effects of polymorphic variation in opioid receptor genes have yielded conflicting results. We examined opioid receptor gene polymorphisms as moderators of the therapeutic effects of the opioid antagonist nalmefene. METHODS Participants (n = 272) were subjects who consented to the pharmacogenetic analysis of a multi-site, randomized, placebo-controlled trial of targeted nalmefene for the reduction of heavy drinking. We genotyped two single nucleotide polymorphisms (SNPs) in OPRM1 (including A118G, a commonly studied SNP that encodes an Asn40Asp amino acid substitution), two SNPs in OPRD1, and one SNP in OPRK1, which encode the mu-, delta-, and kappa-opioid receptors, respectively. Regression analysis served to examine the moderating effects of these SNPs on medication response. RESULTS As previously described by Karhuvaara et al. (2007), nalmefene significantly reduced the number of heavy drinking and very heavy drinking days per week, compared with placebo. There were no main or moderating effects of the genotypes examined on these outcomes. CONCLUSIONS Our finding that the therapeutic effects of targeted nalmefene were not moderated by polymorphic variation in opioid receptor genes is consistent with two recent reports showing that variation in opioid receptor genes does not moderate the response to naltrexone. However, these findings contrast with those from two other studies, in which the Asn40Asp polymorphism in OPRM1 moderated the naltrexone treatment response. Additional research is needed to clarify the role of variation in opioid receptor genes on the response to opioid antagonist treatment of alcoholism.
Referral rates of postlingually deafened adult hearing aid users for a cochlear implant candidacy assessment

Abstract Objective: The aims of this study were: to investigate the referral rates of postlingually deafened adult cochlear implant (CI) candidates from a hearing aid (HA) clinic for a CI candidacy assessment and to gain insight about factors influencing the referral pathways to CI assessments. Design: Two methodologies were used: a retrospective cohort study reviewing clinical files and a questionnaire to clinicians. Study sample: The files of 1249 adult clients from the HA clinic who had average puretone hearing thresholds greater or equal to 65 dB HL in the better hearing ear and unaided phoneme recognition scores of less than 50% in both ears were reviewed. All of the clinicians completed the online questionnaire. Results: Eighteen adults met the CI candidacy criteria, of whom 16 (89%) had a CI discussion with their audiologist, with 11 (61%) being referred for a CI evaluation. Of these 11, four proceeded to implantation. Questionnaire responses revealed the need for better information on candidacy and referral guidelines for HA audiologists, in addition to enhanced communication between HA and CI clinics. Conclusions: Overall the results indicate that the referral pathway to obtain a CI assessment is a barrier contributing to the low CI penetration rate in adults.
Limitations of Energy Expenditure Calculation Based on a Mobile Phone Accelerometer

Sensors available in a mobile device, e.g., a smartphone, a smartwatch, or others, allow the capture of several signals, that may be used to the estimation of the energy expenditure. This paper describes the adaption of a previous research, using different signals and validated with a golden standard, consisting in the comparison between the units of the data acquired by a tri-axial accelerometer and an electromyography signal and the data collected by a mobile device accelerometer. The validation of the system showed that the energy expenditure may not be as correct as expected. The data related to this research is available in an open repository and the platform is available for testing. The creation of a validated method for the measurement of energy expenditure during physical activities capable for the implementation in a mobile application is an important issue to increase the confidence of the mobile applications in this market area.
Properties and functions of Na(+)‐activated K+ channels in the soma of rat motoneurones.

1.Properties and functions of Na(+)‐activated K+ (KNa) channels in the soma of motoneurones were studied in spinal cord slices of newborn rat. KNa channels had a conductance of 44.8 pS in 5.6 mM external K+ (Ko+)/106 mM internal K+ (Ki+) solutions and 139.2 pS in 155 mM Ko+/85 mM Ki+ solutions. KNa channels were voltage independent and needed a relatively high [Na+]i to become active (EC50 = 39.9 mM). Li+ could not substitute for Na+ in activation of KNa channels. The channels were predominantly found in the vicinity of cell processes, in the regions of most probable accumulation of cytoplasmic Na+. 2. In current‐clamp experiments, the shape of the single action potential (AP) recorded in Ca(2+)‐free Ringer solution was not changed after substitution of external Na+ with Li+. However, 0.4‐0.8 s trains of APs were followed by a slow (1‐2s) after‐hyperpolarization (sAHP), which reversibly disappeared when external Na+ was replaced by Li+. Na(+)‐activated sAHP persisted after addition of ouabain and its amplitude was even increased in K(+)‐free Ringer solution. sAHP disappeared when the membrane potential was equal to the K+ equilibrium potential. This indicated that sAHP resulted from activation of a Na(+)‐dependent K+ conductance, rather than from activation of the electrogenic Na(+)‐K+ pump. 3. In conclusion, KNa channels can play an important role in excitability of motoneurones. KNa channels do not make a contribution to the single AP, but they can be activated by a local accumulation of internal Na+ during trains of APs. A Na(+)‐activated K+ conductance can reduce membrane excitability and contribute to regulation of AP firing in motoneurones.
Genetic Variation in the Acute Lethal Response of Four Inbred Mouse Strains to Whole Body X-Irradiation.

HE existence of geneticvariation in radiation sensitivity within a species has been T acknowledged since HENSHAW (1944) reported a difference in the acute lethal response of C3H and LAFl mice to X-radiation. Since that time, strain or genetic differences in the radiation response of small laboratory mammals have been indicated for the sterilization dose (LORENZ et al. 1947), susceptibility to leukemia induction (KIRSCHBAUM and MIXER 1947), changes in blood chemistry (KOHN 1951), hematopoietic response after spleen protection (KAPLAN and PAULI, 1952), changes in body and organ weight (GRAHN 1954a,b) and for the reduction of life expectancy (HENSHAW et al. 1947; EVANS 1948; SACHER 1950; GOWEN 1956). Although the single dose LDSO value is often used in radiobiological studies as an experimental end point, information concerning genetic variation in this value is inadequate. Strain differences in the L D ~ o f llowing X-irradiation are known to exist in mice (LORENZ et al. 1952) and rats (KOHN 1951). RUGH (1953), reviewing several independent studies, indicated that the LDSO value in mice may vary from 400r to 650r of X-rays, depending upon the strain employed. This range of LD50 values is confounded, however, with differences in age a t exposure, radiation quality, and unaccountable environmental factors that certainly must vary among laboratories. No attempt has been made to quantify, in a single experimental effort, strain differences in acute lethality. Consequently, certain features such as age changes in sensitivity, dosage-mortality slopes and sex differenccs are known only in general terms.
Androgen Receptor Phosphorylation

Activation of signal transduction kinase cascades has been shown to alter androgen receptor (AR) activity. Although it has been suggested that changes in AR phosphorylation might be directly responsible, the basal and regulated phosphorylations of the AR have not been fully determined. We have identified the major sites of AR phosphorylation on ARs expressed in COS-1 cells using a combination of peptide mapping, Edman degradation, and mass spectrometry. We describe the identification of seven AR phosphorylation sites, show that the phosphopeptides seen with exogenously expressed ARs are highly similar to those seen with endogenous ARs in LNCaP cells and show that specific agonists differentially regulate the phosphorylation state of endogenous ARs in LNCaP prostate cancer cells. Treatment of LNCaP cells with the synthetic androgen, R1881, elevates phosphorylation of serines 16, 81, 256, 308, 424, and 650. Ser-94 appears constitutively phosphorylated. Forskolin, epidermal growth factor, and phorbol 12-myristate 13-acetate increase the phosphorylation of Ser-650. The kinetics of phosphorylation of most sites in response to hormone or forskolin is temporally delayed, reaching a maximum at 2 h post-stimulation. The exception is Ser-81, which continues to display increasing phosphorylation at 6 h. These data provide a basis for analyzing mechanisms of cross-talk between growth factor signaling and androgen in prostate development, physiology, and cancer.
What is the evidence on evidence-based nursing? An epistemological concern.

AIM This paper adopts an epistemological perspective in order to support the assertion that there is very little evidence to support the existence of evidence-based nursing as a distinct construct or process. RATIONALE This analysis of concept meaning is based on the theory of symbolic interactionism. By adopting this theory the commonalities and inconsistencies in the use of evidence-based symbolism by nurses and other health care professionals can be used to evaluate the perceived meaning of the term. METHODS A frequency analysis of relevant key words in one publications data-base demonstrates the increasing use of evidence-based terminology and its euphemistic status visa vi research. An epistemological analysis is conducted on a sample of concept clarification statements taken from the popular literature, defining the nature of 'evidence' and 'evidence-based practice'. FINDINGS The results of the frequency analysis show that the keywords 'evidence-based medicine' revealed 5612 papers, evidence-based practice (EBP) 432 papers, evidence-based nursing 47 papers, evidence-based health care 60 papers, and evidence-based decision making 43. Almost all of these papers have been published since 1995 and the earliest use of the symbol 'evidence-based' is 1992. There is also an increase in papers adopting 'evidence-based' symbolism along with a commensurate decrease in the use of the term 'research' in the nursing context. CONCLUSION 'Evidence-based practice' is commonly a euphemism for information management, clinical judgement, professional practice development or managed care. There is insufficient evidence to demonstrate that evidence-based nursing is a single construct or process that can be distinguished from its concomitants. The term adds little more to the existing long standing traditions of quality assurance and research-based practice. Nurses must avoid the inefficiency brought about by the 'intense enthusiasm followed by sad disenchantment' that has been associated with other attempts to introduce innovation in health care delivery (Fienstein & Horowitz 1997).
Decomposition strategies for configuration problems

The paper introduces and discusses the notion of decomposition of a configuration problem within the framework of a structured logical approach. The paper describes under which conditions a given configuration problem can be decomposed into a set of noninteracting subproblems and how to exploit such a decomposition, both for improving the performance of the configurator and for supporting interactive configuration. Different kinds of decomposition are considered, but all of them exploit, as much as possible, the explicit representation of the partonomic relations in the language, a KL-One like representation formalism augmented with constraints for expressing complex interrole relations. The paper introduces a notion of boundness among constraints, which is used for formally specifying different types of decomposition. One decomposition strategy aims at singling out the components and subcomponents that are directly related to the constraints put by the user's requirements; the configurator exploits such decomposition by first configuring that portion of the product and then configuring the parts that are not related to the user's requirements. Another decomposition strategy verifies whether the set of constraints for the product to be configured can be split into a set of noninteracting problems. In such a case the configurator solves the configuration problem by splitting the whole search space into a set of smaller search spaces. Different combinations of these two decomposition techniques are considered, and the impact of the decomposition strategies on the performance of the configurator is evaluated via a set of experiments using the configuration of computer systems as a test bed. The results of the experiments show a significant reduction of the computational effort (both in terms of number of backtrackings and in CPU time) when decomposition strategies are used.
Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1. We also identified mutations in KRAS, TP53, and TERT. Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of &ggr;&dgr; T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.
Roles of FliK and FlhB in determination of flagellar hook length in Salmonella typhimurium

The length of flagellar hooks isolated from wild-type and mutant cells with various hook lengths were measured on electron micrographs. The length of the wild-type hook showed a narrow distribution with a peak (+/- standard deviation) at 55.0 +/- 5.9 nm, whereas fliK mutants (so-called polyhook mutants) showed a broad distribution of hook lengths ranging from 40 to 900 nm, strongly indicating that FliK is involved in hook length determination. Among pseudorevertants isolated from such polyhook mutants, fliK intragenic suppressors gave rise to polyhook filaments. However, intergenic suppressors mapping to flhB also gave rise to hooks of abnormal length, albeit they were much shorter than polyhooks. Furthermore, double mutations of flhB and flgK (the structural gene for hook-associated protein 1; HAP1) resulted in polyhooks, suggesting another way in which hook length can be affected. The roles of FliK, FlhB, and HAP1 in hook length determination are discussed.
Consonant‐free words: Evidence from Hebrew speaking children with cochlear implants

This paper reports on a rare phenomenon in language development—the production of words without consonants, and thus syllables without an onset. Such words, which are referred as Consonant‐free words (CFWs), appeared for a short period in the early speech of hearing impaired Hebrew‐speaking children, who produced words consisting of one or two vowels (where the latter were disyllabic). The quantitative data are drawn from the speech of six monolingual hearing‐impaired Hebrew‐speaking children using a cochlear implant device. Their age ranged from 1;5–2;8 years at their first recording session. The elicitation procedure was based on spontaneous speech and picture naming. Findings indicate that cochlear implant users produce CFWs at the initial stage of the prosodic word development. This study claims the CFWs characterize a transitional period between babbling and speech, which varies between different types of populations. The transitional period is rather short in typically developing children, who hardly ever produce CFWs, greater in cochlear implant children, and the greatest in developmental speech disorders such as dyspraxia. Clinical implications of these findings are also discussed.
Price Fluctuations and the Use of Bitcoin: An Empirical Inquiry

ABSTRACT Over recent years, interest has been growing in Bitcoin, an innovation that has the potential to play an important role in e-commerce and beyond. The aim of our paper is to provide a comprehensive empirical study of the payment and investment features of Bitcoin, and their implications for the conduct of e-commerce. Since network externality theory suggests that the value of a network and its take-up are interlinked, we investigate both adoption and price formation. We discover that its returns are driven primarily by Bitcoin’s popularity, the sentiment expressed in newspaper reports on cryptocurrency, and total number of transactions. The paper also reports on the first global survey of merchants who have adopted this technology, and we model the share of sales paid for with this alternative currency, using both ordinary and Tobit regressions. Our analysis examines how country-, customer-, and company-specific characteristics interact with the proportion of sales attributed to Bitcoin. We find that company features, use of other payment methods, customers’ knowledge about Bitcoin, and the size of both the official and unofficial economy are significant determinants. The results will be of interest to traders who seek to understand factors driving prices and will help to inform vendors as to the most favorable circumstances for adopting the currency for online transactions.
FGF/MAPK signaling is required in the gastrula epiblast for avian neural crest induction

Neural crest induction involves the combinatorial inputs of the FGF, BMP and Wnt signaling pathways. Recently, a two-step model has emerged where BMP attenuation and Wnt activation induces the neural crest during gastrulation, whereas activation of both pathways maintains the population during neurulation. FGF is proposed to act indirectly during the inductive phase by activating Wnt ligand expression in the mesoderm. Here, we use the chick model to investigate the role of FGF signaling in the amniote neural crest for the first time and uncover a novel requirement for FGF/MAPK signaling. Contrary to current models, we demonstrate that FGF is required within the prospective neural crest epiblast during gastrulation and is unlikely to operate through mesodermal tissues. Additionally, we show that FGF/MAPK activity in the prospective neural plate prevents the ectopic expression of lateral ectoderm markers, independently of its role in neural specification. We then investigate the temporal participation of BMP/Smad signaling and suggest a later involvement in neural plate border development, likely due to widespread FGF/MAPK activity in the gastrula epiblast. Our results identify an early requirement for FGF/MAPK signaling in amniote neural crest induction and suggest an intriguing role for FGF-mediated Smad inhibition in ectodermal development.
Evaluating the Variance of Likelihood-Ratio Gradient Estimators

The likelihood-ratio method is often used to estimate gradients of stochastic computations, for which baselines are required to reduce the estimation variance. Many types of baselines have been proposed, although their degree of optimality is not well understood. In this study, we establish a novel framework of gradient estimation that includes most of the common gradient estimators as special cases. The framework gives a natural derivation of the optimal estimator that can be interpreted as a special case of the likelihood-ratio method so that we can evaluate the optimal degree of practical techniques with it. It bridges the likelihood-ratio method and the reparameterization trick while still supporting discrete variables. It is derived from the exchange property of the differentiation and integration. To be more specific, it is derived by the reparameterization trick and local marginalization analogous to the local expectation gradient. We evaluate various baselines and the optimal estimator for variational learning and show that the performance of the modern estimators is close to the optimal estimator.
Epidemiology of death in the emergency department of a tertiary health centre south-south of Nigeria.

BACKGROUND The emergency department (E.D) of any hospital is an important entry point of critically ill patients. The initial management of these patients is often challenging, and for valuable lives to be saved, the in fracture and manpower should be up to date. OBJECTIVE To analyze the epidemiology of death in our Emergency Department within 72hours after admission, the death rate, and to establish any contributory factors. METHOD Demographic data, time of arrival at the ED, physical finding, the Glasgow coma scale(GCS), the injury severity score(ISS), the diagnosis, investigations done, treatment offered, the time of death and the autopsy report, were entered into a Proforma. These data was analyzed using EPI-Info statistical programme version 3.4. 3 of 2007. RESULTS Four thousand and eleven (4,011) patients were seen in the E.D during the period. A total of three hundred and fifty five (355) mortalities were recorded. Their ages ranged from 4-87years, with an average of 34.5years. The male: female ratio was 2.1:1. The overall mortality in the hospital during the period was 859: the E.D mortality figure representing 41.3%. Fifteen patients were brought in dead. The 355 deaths fell into two categories: trauma and non-trauma. One hundred and forty-seven (41.4%) persons died from trauma; road traffic accidents (RTAs) accounting for 118 (80.3%). Two hundred and eight (58.6%) persons died from nontrauma related causes, with chronic cardiovascular disorders been the most frequent cause of death 52[25.0]. Majority of the mortalities were between 26-50 years age range. 86.2% of the mortalities presented late, greater than 6hours after the incidence. Within the 72 hours period, only 129(36.3%) were able to do the requested tests. Out of the 355 deaths, only 4[1.1%] were autopsied. An in-hospital 72hours death rate of 8.6 was recorded. CONCLUSION Road traffic accidents and cardiovascular disorders are the common causes of emergency death in UCTH. A recorded death rate of 8.6% is high, suspected contributory factors include systemic deficiencies such as the lack of a trauma system, prehospital care; late presentation, the role of chemist operators, traditional healers, and delayed referral systems.