Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Throughput Screening Assays for the Assessment of CYP2C9*1, CYP2C9*2, and CYP2C9*3 Metabolism Using Fluorogenic Vivid® Substrates

CYP2C9 is a genetically polymorphic human cytochrome P450 isozyme involved in the oxidative metabolism of many drugs, including nonsteroidal anti-inflammatory compounds. Individuals genotyped heterozygous or homozygous for CYP2C9 allelic variants have demonstrated altered metabolism of some drugs primarily metabolized by CYP2C9. The ability to expand screening of CYP2C9 allelic variants to a larger set of drugs and pharmaceutical agents would contribute to a better understanding of the significance of CYP2C9 polymorphisms in the population and to predictions of possible outcomes. The authors report the development of an in vitro fluorescence-based assay employing recombinant CYP2C9 variants (CYP2C9*1, CYP2C9*2, and CYP2C9*3) and fluorogenic Vivid® CYP2C9 substrates to explore the effects of CYP2C9 polymorphisms on drug metabolism, using drugs primarily metabolized by CYP2C9. Several chemically diverse fluorogenic substrates (Vivid® CYP2C9 blue, green, and red substrates) were used as prototypic probes to obtain in vitro CYP2C9 metabolic rates and kinetic parameters, such as apparent Km, Vmax, and Vmax/Km ratios for each allelic variant. In addition, a diverse panel of drugs was screened as assay modifiers with CYP2C9*1, CYP2C9*2, CYP2C9*3, and the fluorogenic Vivid® CYP2C9 substrates. The inhibitory potential of this large group of chemically diverse drugs and compounds has been assessed on the basis of their ability to compete with Vivid® CYP2C9 substrates in fluorescent reporter assays, thus providing a sensitive and quick assessment of polymorphism-dependent changes in CYP2C9 metabolism.
Endoscopic treatment of early oesophageal or gastric cancer.

BACKGROUND AND AIMS: Endoscopic treatment has become increasingly popular in recent years as an alternative to surgical treatment with the hope of offering superior quality of life (QOL) for the patient. The results of endoscopic treatment of mucosal lesions of mostly early oesophageal or gastric cancer performed in 145 patients (155 lesions) over the past eight years were reviewed from the standpoint of QOL. RESULTS: In 56 patients who underwent radical resection of the oesophageal mucosa, no serious complications and symptoms occurred, with epithelialisation completed within about a month. Patients also showed good results regarding dietary intake and performance status (PS), and all are currently alive without any sign of recurrence. One time fractionated endoscopic resection was carried out in about 40% of the 57 patients who underwent gastric mucosal resection. In these 57 patients, an artificial ulcer measuring 3 cm or more was formed, resulting in a favourable outcome after healing. An overwhelming proportion of these subjects had no symptoms and good PS after the treatment. CONCLUSIONS: The introduction of this method, endoscopic mucosal resection using a cap fitted panendoscope, is expected to permit additional indications for endoscopic treatment. Endoscopic Nd-YAG laser irradiation was applied mainly to early gastric cancer lesions (32 patients), usually for relative indications for endoscopic treatment. This procedure is safe and advantageous in that it requires no hospitalisation, permits fractionated irradiation, and secures good QOL.
Vegetation replacement in Rio de Janeiro during the last 7,000 years B.C., genetic variation in the medicinal plant Lippia alba (Verbenaceae), and short review of Chagas disease in prehistory.

(AABC) presents an important contribution thatsheds new light on this problem. Luz et al. (2011) have studied two core samples from the municipality of Camposdos Goytacazes, located in the northern costal region of Rio de Janeiro. Their aim was to understand the changes ofthe vegetation during the last 7,000 years B.C. based on palynological evidences. Palynomorphs have already beenfound in this region (e.g., Luz et al. 2010), but were not studied in detail throughout the cores.Luz et al. (2011) have shown that there were changes in successions of vegetational patterns, some due to floodingevents during the Holocene and others as a response to sea level changes. However, no evidence of the use of fire orother agricultural activities by the Goitacas Indians was showed in the cores studied by these authors. This contradictstheories that have at least partially attributed the actions of these indigenous groups to the origin of these fields.Another interesting study published in this volume of the AABC is on the genetic variation in
The contribution of hydroxyl radical to radiosensitization: a study of DNA damage.

Using the radioprotector dimethylsulfoxide, DMSO, as a scavenger of hydroxyl radicals, the proportions of DNA damage caused by OH. were determined in mammalian cells irradiated in hypoxia with or without the radiosensitizers misonidazole and TAN or in air. Yields of both single-strand breaks (SSB) and base/sugar damage (MLS for Micrococcus luteus sensitive sites) were measured for each situation. Most of the damage enhanced by the sensitizers was found to be OH. dependent, for both MLS and SSB classes of damage: most breaks (greater than 80%) enhanced by oxygen and about two-thirds of the breaks enhanced by misonidazole (hypoxia) occur at OH. -damaged sites; most if not all base/sugar damage enhanced by the sensitizers misonidazole and TAN (in hypoxia) occurs only in the presence of OH. , whereas in air, some (about one-quarter) of the enhanced MLS damage does not require OH. The sensitizer enhancement ratios in the presence of scavenger and the degree of protection afforded by the scavenger determined for total (MLS + SSB) damage agree well with those derived from corresponding survival experiments.
Simulation Fellowship Programs: An International Survey of Program Directors

Purpose To report on the evolution of simulation-based training (SBT) by identifying the composition and infrastructure of existing simulation fellowship programs, describing the current training practices, disclosing existing program barriers, and highlighting opportunities for standardization. Method Investigators conducted a cross-sectional survey study among English-speaking simulation fellowship program directors (September 2014–September 2015). They identified fellowships through academic/institutional Web sites, peer-reviewed literature, Web-based search engines, and snowball sampling. They invited programs to participate in the Web-based questionnaire via e-mail and follow-up telephone calls. Results Forty-nine programs met the inclusion criteria. Of these, 32 (65%) responded to the survey. Most programs were based in the United States, but others were from Canada, England, and Australia. Over half of the programs started in or after 2010. Across all 32 programs, 186 fellows had graduated since 1998. Fellows and directors were primarily departmentally funded; programs were primarily affiliated with hospitals and/or medical schools, many of which had sponsoring centers accredited by governing bodies. Fellows were typically medical trainees; directors were typically physicians. The majority of programs (over 90%) covered four core objectives, and all endorsed similar educational outcomes. Respondents identified no significant universal barriers to program success. Most directors (18/28 [64%]) advocated standardized fellowship guidelines on a national level. Conclusions Paralleling the fast growth and integration of SBT, fellowship training opportunities have grown rapidly in the United States, Canada, and beyond. This study highlights potential areas for standardization and accreditation of simulation fellowships which would allow measurable competencies in graduates.
A novel visual sputum suctioning system is useful for endotracheal suctioning in a dog model.

OBJECTIVE This study is to test the effectiveness of fiber-optic-guided endotracheal suction catheter (visual sputum suctioning system or VSSS) in dog models. METHODS Dog sputum models were established by administering dimethoate emulsifiable. Twenty-seven intubated dogs were equally randomized into three groups of conventional suctioning (CS) group, VSSS with no supplemental oxygen (VSSS) group and VSSS with 100% oxygen (VSSS/O2) group. The suctioning efficiency, vital signs and tracheal wall injury were assessed. RESULTS The VSSS/O2 (8.6 ± 0.7g) and VSSS groups (8.5 ± 0.9 g) collected significantly more sputum than the CS group (5.9 ± 0.8 g) (P < 0.05 for VSSS/O2 group versus CS group; P < 0.05 for VSSS group versus CS group). Immediately after suctioning, the arterial partial pressure of oxygen (PaO2 ) of VSSS/O2 group was significantly higher than that of the VSSS group or the CS group (both P < 0.05), and 5 min after suction the PaO2 , the mean arterial pressure (MAP) and heart rate (HR) in all groups returned to the baseline (p = 0.54, P = 0.67, P = 0.11, respectively). Moreover, in the VSSS/O2 and VSSS groups all the three variables were higher than the CS group at 5 min after suctioning (P < 0.01, P = 0.03; P = 0.02, P < 0.01; P = 0.02, P = 0.01 respectively). CONCLUSIONS Visual sputum suctioning system collected more sputum and caused less tracheal mucosa damage than conventional suctioning.
An Examination of the Word Memory Test as a Measure of Memory

This study examined the utility of the Word Memory Test (WMT) as a measure of verbal episodic memory by comparing select WMT subtests to the California Verbal Learning Test (CVLT) First and Second Editions (CVLT-II) across two samples. Correlations between the WMT and CVLT/CVLT-II subtests were statistically significant in the expected direction. Effect sizes were examined to assess the degree to which the WMT memory subtests and the CVLT First Edition subtests discriminated between groups of people who would be expected to differ from each other in verbal memory abilities. Comparison groups included cases of mild, moderate, and severe traumatic brain injury, mixed neurological patients, healthy adult controls, and patients with possible early dementia. Once invalid data were removed by studying only those who passed performance validity testing, it was found that the effect sizes between these groups were comparable. The WMT, CVLT, and CVLT-II were found to discriminate to about the same degree between people differing from each other in age, intelligence levels, and gender. Based on these data from a total sample of more than 3,000 cases, it is concluded that select WMT subtests are commensurate with the CVLT subtests as measures of memory within primarily disability-seeking samples.
Magnetic Resonance Imaging Aids in Detecting Concomitant Injuries in Patients with Tibial Spine Fractures

Tibial spine fracture is one of the clinical entities of anterior cruciate ligament injury, and sometimes is accompanied by concomitant injuries. The purpose of this study was to review magnetic resonance imaging findings in 25 patients with tibial spine fractures and to assess the use of these findings in determining the presence of concomitant injuries. Of these 25 patients, 10 were children and 15 were considered adults (average age, 24.2 years old). A radiologist retrospectively assessed tibial spine fractures and concomitant injuries, such as meniscus and ligament injuries. Comparing the pediatric and adult groups, all additional ligament injuries were confirmed in the adult group. In the pediatric group, only one patient with a chronic injury had meniscus injuries. There were no meniscus tears in pediatric patients with acute injuries. In the adult group, three medial meniscus tears were found in two patients with chronic injuries and one patient with acute injury, and four lateral meniscus tears were found in one patient with a chronic injury and three patients with acute injuries. Because tibial spine fractures in adults may be accompanied by concomitant injuries requiring surgical treatment, magnetic resonance imaging is recommended. Level of Evidence: Diagnostic study, Level III-1 (study of nonconsecutive patients—no consistently applied reference “gold” standard). See the Guidelines for Authors for a complete description of levels of evidence.
Optimization of prednisolone acetate-loaded chitosan microspheres using a 23 factorial design for preventing restenosis

Prednisolone acetate (PA)-loaded microspheres were prepared by the spray-drying technique using different polymer (1% and 2%) and drug concentrations (10% and 20%). To obtain the optimum formulation, a three-factor two-level (23) design was employed. The independent variables were polymer molecular weight, polymer concentration, and theoretical drug loading. Responses were the particle size, percentage of encapsulation efficiency, and the t50% release. The best formulation was prepared with 20% of PA and 1% of chitosan with medium molecular weight showing relative good yield of production (48.0 ± 6.7%) and encapsulation efficiency (45.7 ± 0.3%), and released the drug at a constant rate in 11 days.
Prospective Surveillance for Primary Bloodstream Infections Occurring in Canadian Hemodialysis Units

Objective: Bloodstream infections are a major cause of morbidity and mortality in patients receiving long-term hemodialysis. We wanted to determine the incidence of hemodialysis-related bloodstream infections in Canadian centers participating in the Canadian Nosocomial Infection Surveillance Program. Methods: Prospective surveillance for hemodialysis-related bloodstream infections was performed in 11 centers during a 6-month period. Bloodstream infections were defined by published criteria. Hemodialysis denominators included the number of dialysis procedures, the number of patient-days on dialysis, and the frequencies of different types of vascular access. Results: There were 184 bloodstream infections in 133,158 dialysis procedures (1.4 per 1,000) and 316,953 patient-days (0.6 per 1,000). Hemodialysis access through arteriovenous (AV) fistulae was associated with the lowest risk for bloodstream infection (0.2 per 1,000 dialysis procedures). The relative risk for infection was 2.5 with AV graft access, 15.5 with cuffed and tunneled central venous catheter (CVC) access, and 22.5 with uncuffed CVC access (P < .001). There was marked variation among the 11 centers in the means of vascular access used for hemodialysis. Significant variation in infection rates was observed among the centers when controlling for types of access. Conclusions: There was a hierarchy of risk of hemodialysis-related bloodstream infection according to type of vascular access. There was significant variation in the type of vascular access being used among the Canadian hemodialysis centers, and also variation in access-specific infection rates between centers.
Antioxidant treatments do not improve force recovery after fatiguing stimulation of mouse skeletal muscle fibres

Increased free radical production may contribute to decreased muscle force production during fatiguing exercise, and might delay recovery from fatigue. We exposed mouse fast‐twitch single fibres to antioxidants targeting specific cellular sites to determine whether these compounds delay fatigue development and/or improve the recovery from fatigue. Antioxidants had no effect on the fatigue‐induced decrease in contractile force. During recovery from fatigue, a mitochondria‐targeted antioxidant, SS‐31, restored the fatigue‐induced decrease in sarcoplasmic reticulum Ca2+ release, but did not improve force recovery. We conclude that antioxidants cannot counteract the force decline during or after induction of muscle fatigue, although they may affect the underlying mechanisms.
Molecular Determinants for Subcellular Localization of Hepatitis C Virus Core Protein

ABSTRACT Hepatitis C virus (HCV) core protein is a putative nucleocapsid protein with a number of regulatory functions. In tissue culture cells, HCV core protein is mainly located at the endoplasmic reticulum as well as mitochondria and lipid droplets within the cytoplasm. However, it is also detected in the nucleus in some cells. To elucidate the mechanisms by which cellular trafficking of the protein is controlled, we performed subcellular fractionation experiments and used confocal microscopy to examine the distribution of heterologously expressed fusion proteins involving various deletions and point mutations of the HCV core combined with green fluorescent proteins. We demonstrated that a region spanning amino acids 112 to 152 can mediate association of the core protein not only with the ER but also with the mitochondrial outer membrane. This region contains an 18-amino-acid motif which is predicted to form an amphipathic α-helix structure. With regard to the nuclear targeting of the core protein, we identified a novel bipartite nuclear localization signal, which requires two out of three basic-residue clusters for efficient nuclear translocation, possibly by occupying binding sites on importin-α. Differences in the cellular trafficking of HCV core protein, achieved and maintained by multiple targeting functions as mentioned above, may in part regulate the diverse range of biological roles of the core protein.
Red meat, diseases, and healthy alternatives: A critical review

ABSTRACT Meat is an important food for human nutrition, by especially providing high-quality protein and also some essential micronutrients, in front iron, zinc, and vitamin B12. However, a high intake of red and processed meat is associated with an increased risk for diseases, especially type 2 diabetes and colorectal cancer, as several epidemiological studies and meta-analyses have shown. This review summarizes meta-analyses of publications studying the association between red and processed meat intake and type 2 diabetes, cardiovascular diseases, colorectal and other cancers, and all-cause mortality. Various potential mechanisms involved in the increased disease risk are discussed. Furthermore, the beneficial effects of healthy alternatives for meat, like fish, nuts, vegetables and fruits, pulses and legumes, whole grains, and dairy products are reviewed by including selected papers and recent meta-analyses.
A novel source of resistance in lentil (Lens culinaris ssp. culinaris) to ascochyta blight caused by Ascochyta lentis

The lentil accession ILL7537 was resistant in glasshouse bioassays to isolates of Ascochyta lentis Vassilievsky from a range of Australian pathotype groups, confirming its status as a highly resistant cultivated accession. Two dominant complementary genes were determined to condition the genetic mechanism and mode of inheritance of resistance in ILL7537. Accession ILL7537 was screened with molecular markers that were linked to, and flanking, the major resistance gene AbR1 from the accession ILL5588. The absence of all of the markers from the AbR1 linkage group indicated that the resistance mechanism in ILL7537 was potentially novel.
A phenomenological study of music teachers' approaches to inclusive education practices among disaffected youth

The drive for 'inclusion' has become a prominent feature in UK educational policy agendas and school improvement programmes. The term refers to all children achieving and participating despite challenges stemming from poverty, class, race, religion, linguistic and cultural heritage or gender. While much has been written about inclusion, evidence on how teachers perceive inclusive education practices among young people who are disengaged from learning and educational opportunity (as manifested by non-attendance or under-achievement at school) has been less thoroughly explored. This multiple case study draws on research on secondary school music teachers in 'poorly performing', so-called 'under-achieving' schools, including three comprehensive secondary schools in the east and south-east regions of England. It reports on what it is that three music teachers can tell us about their beliefs and approaches to inclusive teaching and learning in their pedagogical settings. A phenomenological approach utilizing semi-structured interview was employed to explore music teachers' perceptions of what it is that they think they do in responding to and overcoming the challenge of re-engaging disaffected youth - their perceptions of their own inclusive pedagogic practices. In order to explore the teachers' perceptions further, some artefact prompts in interviews, such as curriculum planning documents, were employed to provide an opportunity to discuss key factors concerning the content of the music courses. The findings emphasize that, for these teachers, inclusive pedagogies involve more than the accumulation of teaching strategies employed by teachers for supporting troubled and troublesome learners. These teachers' pedagogies are informed largely by particular views of music, views of musical learning and learners, views of the kind of knowledge that is created and the educational outcomes that are desired in overcoming the particular challenges of attuning to and re-engaging disaffected learners. Inclusive pedagogic practices in this study were foregrounded and framed by attuning to and re-engaging disaffected learners by: (a) democratizing music learning as social practice; (b) foregrounding high-status creative projects; and (c) using digital technology as pedagogic levers for re-engaging learners. The emergent themes provide a preliminary basis for theorizing about the role of music education in the schooling of disaffected youth.
The growth of the eye and its components: Japanese studies

Fig. 1 compiles the refractive distribution curves of Wibaut (1926), Goldschmidt (1969) and by myself (1962). The distributions of refraction in the new-born babies appear very similar in different countries and in different eras. There is a peak by hypermetropia about 1-2 diopters, and the frequency of myopia is only 5%. In the following years, elongation of the ocular axis, relative thinning of the crystalline lens and flattening of the cornea lead to a change so that most children are emmetropic at the age of 8 to 10 years.
Breast conservation after neoadjuvant chemotherapy

The appropriate selection criteria for breast‐conserving therapy (BCT) after neoadjuvant chemotherapy are poorly defined. The purpose of the current report was to develop a prognostic index to help refine selection criteria and to serve as a general framework for clinical decision‐making for patients treated by this multimodality approach.
Fiscal Consolidation As a Self-Fulfilling Prophecy on Fiscal Multipliers

Fiscal policy may affect the size of the fiscal multiplier or lengthen the elevated multipliers period. This notion at first seems controversial, however it is only an outcome of combining two strands of already available literature together. The first strand touches the effects of fiscal policy on economic situation, the second one suggests economic situation affects fiscal multiplier. Having those two premises implies that fiscal policy could indirectly influence the fiscal multiplier size or the length of the elevated multiplier period. This possibility is fitted into a simple model of liquidity trap with hysteresis effects. One of the main outcomes of the model is that, when the government expectations on the size of the fiscal multiplier influence fiscal actions - as it is possibly the case - those expectations may become selffulfilling prophecies.