Miracle-dz/UniFAR-FTUs huggingface dataset:
Cocktail-substrate assay system for mechanism-based inhibition of CYP2C9, CYP2D6, and CYP3A using human liver microsomes at an early stage of drug development

We established a mechanism-based inhibition cocktail-substrate assay system using human liver microsomes and drug–probe substrates that enabled simultaneous estimation of the inactivation of main cytochrome P450 (CYP) enzymes, CYP2C9, CYP2D6, and CYP3A, in drug metabolism. The inactivation kinetic parameters of typical mechanism-based inhibitors, tienilic acid, paroxetine, and erythromycin, for each enzyme in the cocktail-substrate assay were almost in agreement with the values obtained in the single-substrate assay. Using this system, we confirmed that multiple CYP inactivation caused by mechanism-based inhibitors such as isoniazid and amiodarone could be detected simultaneously. Mechanism-based inhibition potency can be estimated by the determination of the observed inactivation rate constants (kobs) at a single concentration of test compounds because the kobs of eleven CYP3A inactivators at 10 μM in the assay system nearly corresponded to kinact/KI values, an indicator of a compound’s propensity to alter the activity of a CYP in vivo (R2 = 0.97). Therefore, this cocktail-substrate assay is considered to be a powerful tool for evaluating mechanism-based inhibition at an early stage of drug development.
Walk a Mile in Their Shoes: Implementing Family‐Centered Care in Serving Children and Families Affected by Autism Spectrum Disorder

It is critical that speech–language pathologists and other service providers understand the specifics of applied family-centered practice. This article presents a qualitative study that describes these specifics and provides an example of applied family-centered practice through the experiences of graduates of the Vermont Rural Autism Project. The Vermont Rural Autism Project was a 3-year grant-funded project that trained speech–language graduate students and related professionals in family-centered assessment and intervention for children with autism (J. E. Beatson & P. A. Prelock, 2002). Ten trainee participants were interviewed using a standardized, open-ended interview guide (M. Patton, 1990). Data were coded and organized into several themes. Most interviewees reported that their values, beliefs, and practice were transformed through their experiences with families, coupled with the increased knowledge and skills in collaborative teaming, assessment, and intervention in autism they acquired through the program. Practice implications are discussed.
On Being Holier-Than-Thou or Humbler-Than-Thee: A Social-Psychological Perspective on Religiousness and Humility

This research examined the association between religiousness and humility. Participants in Studies 1 and 2 completed measures of religiousness, socially desirable responding, and their own and other people’s adherence to biblical commandments. Participants in Study 2 also rated how characteristic nonreligious positive and negative trait terms were of the self and others. Humility was operationalized as the magnitude of difference between individuals’ evaluations of self and other. Overvaluing the self in relation to others or undervaluing others in relation to the self was considered evidence of less humility. Participants rated the self to be more adherent to biblical commandments than others (the holier-than-thou effect) and rated the self to be more positive and less negative than others (the self-other bias). In both studies, intrinsic religiousness was associated with an increase in the tendency to rate the self as more adherent to biblical commandments than others. Quest was associated with a slight decrease in the magnitude of the holier-than-thou effect. Religious motivations did not account for unique variation in the general self-other bias. Irrespective of motivations for being religious, however, highly religious people (i.e., upper thirds on general religiousness and religious fundamentalism) more so than less religious people (i.e., lower thirds on general religiousness and religious fundamentalism) rated the self to be better on nonreligious attributes than others.
The ethics of protocells : moral and social implications of creating life in the laboratory

Teams of scientists around the world are racing to create protocells--microscopic, self-organizing entities that spontaneously assemble from simple organic and inorganic materials. The creation of fully autonomous protocells--a technology that can, for all intents and purposes, be considered literally alive--is only a matter of time. This book examines the pressing social and ethical issues raised by the creation of life in the laboratory. Protocells might offer great medical and social benefits and vast new economic opportunities, but they also pose potential risks and threaten cultural and moral norms against tampering with nature and "playing God. " The Ethics of Protocells offers a variety of perspectives on these concerns. After a brief survey of current protocell research (including the much-publicized "top-down" strategy of J. Craig Venter and Hamilton Smith, for which they have received multimillion dollar financing from the U.S. Department of Energy), the chapters treat risk, uncertainty, and precaution; lessons from recent history and related technologies; and ethics in a future society with protocells. The discussions range from new considerations of the precautionary principle and the role of professional ethicists to explorations of what can be learned from society's experience with other biotechnologies and the open-source software movement. Contributors: Mark A. Bedau, Gaymon Bennett, Giovanni Boniolo, Carl Cranor, Bill Durodie, Mickey Gjerris, Brigitte Hantsche-Tangen, Christine Hauskeller, Andrew Hessel, Brian Johnson, George Khushf, Emily C. Parke, Alain Pottage, Paul Rabinow, Per Sandin, Joachim Schummer, Mark Triant, Laurie Zoloth
Medical Outcomes in African American Live Kidney Donors: A Matched Cohort Study

It is uncertain if live kidney donation increases future risk of hypertension and kidney disease in African Americans. We conducted a cohort study across two transplant centers enrolling African Americans who donated between 1993 and 2006. A comparison group of African American nondonors were selected from healthy participants in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study. A total of 103 donors and 235 matched nondonors were assessed at mean ( ± SD) of 6.8 ± 2.3 and 6.4 ± 2.2 years after donation or cohort entry, respectively. The primary outcome was risk of hypertension in donors at follow‐up. The secondary outcomes were proportion of donors with eGFR <60 mL/min/1.73 m2 and microalbuminuria. Hypertension risk was higher in donors compared to nondonors (42/103 [40.8%] vs. 42/235 [17.9%]), absolute risk difference 22.9% (95% confidence interval 12.2–33.6%) and relative risk 2.4 (95% confidence interval 1.7–3.4). Of the 42 donors with hypertension, 22 (52.4%) were untreated. Sixteen donors (15.5%) had an eGFR <60 mL/min/1.73 m2, 6 (5.8%) had microalbuminuria and none were on dialysis. Our retrospective study shows that live kidney donation is associated with increased risk of hypertension in African Americans and emphasizes the importance of donor follow‐up.
High Fasting Plasma Glucose Mortality Effect: A Comparative Risk Assessment in 25–64 Years Old Iranian Population

Background: High fasting plasma glucose (FPG) is one of the main leading risk factors of ischemic heart disease (IHD), stroke, and chronic kidney diseases (CKDs). We estimated population attributable fraction (PAF) and attributed death of these fatal outcomes of high FPG at national and subnational levels in 25–64 years old Iranian adult. Methods: We used national and subnational data of the Non-Communicable Disease Surveillance Survey for exposure to risk factors in 2005 and 2011 among Iranian adults of 25–64 years old. For estimating the attributed death, using the death registration system data of Iran, we multiply the cause-specific PAFs by the number of outcome-specific deaths. Results: In Iran, high FPG was responsible for about 31% of attributed total deaths of IHD, stroke, and CKD in 2011. The related attributed deaths had increased from 2005 to 2011. In females, the PAFs for the effect of high FPG on IHD, stroke, and CKD were higher in 2011 than 2005 in all age groups. In males, this increase has occurred in over 45 years old. The highest PAFs of high FPG outcomes mostly related to central provinces of Iran. The central region of Iran had the highest and the southeast of the country had the lowest levels of attributed deaths. Conclusions: Considering the global 25 × 25 targets for noncommunicable disease mortality reduction, high FPG as a leading risk factor of fatal outcomes should be more targeted through the dietary, behavioral, and pharmacological interventions in Iran.
What's in a Story? The Relationship Between Narrative Completeness and Adjustment to Relationship Dissolution

The construction of narratives has been shown to assist sufferers of emotional or traumatic events - such as the ending of relationships - in making sense of and coming to terms with the event. Despite this connection, few studies have explored how the completeness of the narratives contributes to positive outcomes. Building on research in both communication and psychology, we conceptualized a complete narrative as one that clearly and extensively (1) segmented the experience episodically/sequentially, (2) represented causes and consequences in the explained events, (3) developed characters relative to the story, (4) evoked and made sense of affect, (5) drew meaning from the events in the narrative, (6) provided a coherent narrative, and (7) attributed responsibility to the characters in the story. We collected and analyzed the break-up stories of 90 participants. We then rated the narratives to see if relationships exist between narrative completeness and adjustment to relationship dissolution as well as to the teller's role in the break-up and his or her current relationship status. In addition to the implementation of a new method for coding and analyzing narrative content, the results indicate that certain elements of completeness are more related to adjustment than are others.
Recreation Specialisation among New Zealand Whitewater Kayakers: A study of motivation and site preference

Abstract The purpose of this study was to examine the relationship of specialisation to motivations and site preferences among whitewater kayakers. Subjects consisted of 358 whitewater kayakers in New Zealand. Data was collected via an internet survey in New Zealand in 2008. Research questions addressed the delineation between levels of specialisation and associated relationships with motivation and site preference variables. Results found that high levels of motivation and site preference for wilderness values, enjoyment of nature, similar people, achievement, and physical fitness were supportive of a social world perspective, regardless of the specialisation level. Specialisationrelated differences emerged for achievement, teaching others, and challenge/safety. Low motivation and preference were found for introspection, family togetherness, escape, equipment, facilities, and novelty. Hammett, Backlund, and Bixler (2004) indicate that recreation resource managers would find this information to be instrumental in aiding future policy and planning decisions.
Psychosocial Correlates of Adolescent Cannabis Use: Data from the Italian Subsample of the Second International Self-Reported Delinquency Study

To provide a comprehensive picture of the whole spectrum of psychosocial factors potentially associated with adolescent cannabis use, bivariate and multivariate analyses were used to assess a variety of social, demographic, psychological, and behavioral correlates of last-month cannabis use and age of first use among 6,838 students. Results showed that only family problems, alcohol and/or other drug use/misuse, deviant behavior, and victimization were independently associated with either recent cannabis use or early onset of cannabis use when multiple, interacting factors were considered. Certain family and behavioral factors might be more important than other psychosocial correlates of adolescent cannabis use.
Self‐directed work groups and team competence

The study examines the impact of self-directed group work on team competence. The sample consists of 83 production groups from 20 medium-sized enterprises: 44 self-directed work groups and 39 traditional work groups. Results based on process-analytic behavioural data, collected at the group level of analysis, show that self-directed teams are more competent than traditional work groups on seven out of 12 aspects of competence. Self-directed teams show greater methodological competence, to some extent greater professional and self-competence but no greater social competence when completing optimization tasks. In addition, the work characteristics participation, formal team communication, continuous improvement process, training and team-oriented tasks were related to team competence in the subsample of self-directed work teams.
AIDS in the twenty-first century: Disease and globalization

guided by statistics. It concerns the intersection between religion and death, and what this might tell us about ourselves and our societies, and it succeeds admirably in this task. Most authors adopt theories to elucidate the social aspects of death, and religion’s role in this. Berger’s sacred canopy looms large, and Douglas Davies helpfully explains the role of theory and interpretation (p. 229). Terms which might perplex non-specialist readers have been unobtrusively glossed as they occur, and one senses a laudable editorial attention to detail, though some misplaced and repeated text occurs on p. 98 and on p. 298. I would have liked to know what a sand dollar is (Echinarachnius parma). Some authors use their data to challenge prevailing theories or models; Denis Kelley rejects the view that academics can identify ‘‘authentic’’ Native American practices, and posits the notion of a ‘‘reprise’’ rather than authenticity or continuity of tradition, while Tony Walter, who sees the media taking on the role of religions, bending narratives of tragedy into stories of hope (but regardless of the feelings of those closely involved), challenges (p. 280) the Giddens and Mellor/Shilling view that death has been sequestered. I wonder, however, if the strict self-censorship imposed by Western media outlets which seldom show damaged bodies is a kind of sequestration by propriety. Mark Elmore’s Hindus in Himachal Pradesh (p. 30) have a humorous approach to death, except when it actually happens and solemn ritual takes over. Surely the plethora of humorous synonyms for death in English (most of them rehearsed in the Monty Python ‘‘dead parrot’’ sketch) suggests that humour except in the face of death is not a particularly Hindu trait.
Extramarital sex: A review of the research literature

Abstract Research literature in the field of extramarital sex (EMS) is reviewed. Initially, definitional problems which reveal the need for increased rigor in specifying the sexual behavior under consideration, the dyad or group outside of which the behavior occurs, and the consensual or non‐consensual nature of the behavior are discussed. Twelve surveys of EMS are examined and the limitations of incidence rate figures discussed. Empirical studies have attempted to identify key variables which discriminate between EMS and non‐EMS samples. The findings of this research are summarized according to four variable categories: social background characteristics, characteristics of the marriage, personal readiness characteristics, and sex and gender differences. Characteristics of the marriage and personal readiness characteristics are found to be of prime importance in understanding EMS, although sex and gender differences frequently qualify major empirical relationships. The attitude continuum of extramarital s.
Bloodlands: Europe between Hitler and Stalin

Tim Snyder’s ambitious Bloodlands set out to place the murderous regimes of the Third Reich and Stalin’s Soviet Union in their overlapping European contexts. Snyder proceeded from the central observation that the annihilation fantasies of Hitler and Stalin were to a large part played out in the same space: ‘in the middle of Europe, in the middle of the twentieth century, the Nazi and Soviet regimes murdered some 14 million people. The place where all of the victims died, the bloodlands, extends from central Poland to western Russia, through Ukraine, Belarus, and the Baltic states’ (pp. vii-viii) And yet, Snyder argued, these histories were seldom considered together – not least because the Holocaust overshadows all as a result of its dominance in modern memory cultures, preventing understanding of a wider culture and history of murder and annihilation.
Estimating Species Richness and Modelling Habitat Preferences of Tropical Forest Mammals from Camera Trap Data

Medium-to-large mammals within tropical forests represent a rich and functionally diversified component of this biome; however, they continue to be threatened by hunting and habitat loss. Assessing these communities implies studying species’ richness and composition, and determining a state variable of species abundance in order to infer changes in species distribution and habitat associations. The Tropical Ecology, Assessment and Monitoring (TEAM) network fills a chronic gap in standardized data collection by implementing a systematic monitoring framework of biodiversity, including mammal communities, across several sites. In this study, we used TEAM camera trap data collected in the Udzungwa Mountains of Tanzania, an area of exceptional importance for mammal diversity, to propose an example of a baseline assessment of species’ occupancy. We used 60 camera trap locations and cumulated 1,818 camera days in 2009. Sampling yielded 10,647 images of 26 species of mammals. We estimated that a minimum of 32 species are in fact present, matching available knowledge from other sources. Estimated species richness at camera sites did not vary with a suite of habitat covariates derived from remote sensing, however the detection probability varied with functional guilds, with herbivores being more detectable than other guilds. Species-specific occupancy modelling revealed novel ecological knowledge for the 11 most detected species, highlighting patterns such as ‘montane forest dwellers’, e.g. the endemic Sanje mangabey (Cercocebus sanjei), and ‘lowland forest dwellers’, e.g. suni antelope (Neotragus moschatus). Our results show that the analysis of camera trap data with account for imperfect detection can provide a solid ecological assessment of mammal communities that can be systematically replicated across sites.
The Electoral Behavior of the Poor in Brazil: A Research Agenda

Some deem the Bolsa Família program (BF) in Brazil to be a quintessentially clientelistic tool, thought to have produced colossal sociodemographic transformations in the base of support of President Luiz Inácio Lula da Silva, particularly in the 2006 election. An earlier article (Bohn 2011) maintained that significant changes in Lula’s electoral base took place prior to his reelection; other social policies, such as the Benefício de Prestação Continuada, contributed significantly to the changes in Lula’s camp; and, most important, that the link between the receipt of social benefits and vote is less straightforward than those who view Bolsa Família as a clientelistic program assume it to be. This work addresses some of the criticisms that the article received and reinforces the need for further research that uses individual-based data to disentangle the complexity of the electoral behavior of the poor in highly unequal societies.
Self-Configuring and Evolving Fuzzy Image Thresholding

Every segmentation algorithm has parameters that need to be adjusted in order to achieve good results. Evolving fuzzy systems for adjustment of segmentation parameters have been proposed recently (Evolving fuzzy image segmentation -- EFIS [1]). However, similar to any other algorithm, EFIS too suffers from a few limitations when used in practice. As a major drawback, EFIS depends on detection of the object of interest for feature calculation, a task that is highly application-dependent. In this paper, a new version of EFIS is proposed to overcome these limitations. The new EFIS, called self-configuring EFIS (SC-EFIS), uses available training data to auto-configure the parameters that are fixed in EFIS. As well, the proposed SCEFIS relies on a feature selection process that does not require the detection of a region of interest (ROI).
HIV Prevention and Rehabilitation Models for Women Who Inject Drugs in Russia and Ukraine

Women who inject drugs require gender-specific approaches to drug rehabilitation, modification of risk behaviors, and psychosocial adaptation. Improved outcomes have been demonstrated when the specific needs of women's subpopulations have been addressed. Special services for women include prenatal care, child care, women-only programs, supplemental workshops on women-focused topics, mental health services, and comprehensive programs that include several of the above components. To address the special needs of women injecting drug user (IDU) subpopulations, such as HIV-positive pregnant women and women with young children, recently released female prisoners, and street-involved girls and young women, HealthRight International and its local partners in Russia and Ukraine have developed innovative service models. This paper presents each of these models and discusses their effectiveness and implementation challenges specific to local contexts in Russia and Ukraine.
Cynomolgus Monkey as a Surrogate for Human Aldehyde Oxidase Metabolism of the EGFR Inhibitor BIBX1382

BIBX1382 was an epidermal growth factor receptor inhibitor under clinical investigation for treatment of cancer. This candidate possessed an attractive preclinical absorption, distribution, metabolism, and excretion profile, yet failed in clinical studies due in part to poor oral exposure, resulting from extensive metabolism by aldehyde oxidase (AO). In vitro metabolism studies were performed in liver cytosol and cryopreserved hepatocytes from multiple species. In addition, a pharmacokinetic study was performed in cynomolgus monkey for comparison with the reported human pharmacokinetics of BIBX1382. Estimated hepatic clearance of BIBX1382 in rhesus (42 ml/min per kg) and cynomolgus monkey (43 ml/min per kg) liver cytosol was comparable to human (≥93% of liver blood flow). Metabolite identification after incubation of BIBX1382 in liver cytosol fortified with the AO inhibitor raloxifene confirmed that AO is involved in the formation of the predominant metabolite (BIBU1476, M1) in cynomolgus monkey. After intravenous and oral administration of BIBX1382 to cynomolgus monkeys, high plasma clearance (118 ml/min per kg) and low oral exposure (Cmax = 12.7 nM and 6% oral bioavailability) was observed, with the exposure of M1 exceeding BIBX1382 after oral dosing. This pharmacokinetic profile compared favorably with the human clinical data of BIBX1382 (plasma clearance 25–55 ml/min per kg and 5% oral bioavailability). Thus, it appears that cynomolgus monkey represents a suitable surrogate for the observed human AO metabolism of BIBX1382. To circumvent clinical failures due to uncharacterized metabolism by AO, in vitro studies in the appropriate subcellular fraction, followed by pharmacokinetic and toxicokinetic studies in the appropriately characterized surrogate species should be conducted for substrates of AO.