Miracle-dz/UniFAR-FTUs huggingface dataset:
THE EVOLUTION OF GENETIC ARCHITECTURE UNDER FREQUENCY-DEPENDENT DISRUPTIVE SELECTION

Abstract We propose a model to analyze a quantitative trait under frequency-dependent disruptive selection. Selection on the trait is a combination of stabilizing selection and intraspecific competition, where competition is maximal between individuals with equal phenotypes. In addition, there is a density-dependent component induced by population regulation. The trait is determined additively by a number of biallelic loci, which can have different effects on the trait value. In contrast to most previous models, we assume that the allelic effects at the loci can evolve due to epistatic interactions with the genetic background. Using a modifier approach, we derive analytical results under the assumption of weak selection and constant population size, and we investigate the full model by numerical simulations. We find that frequency-dependent disruptive selection favors the evolution of a highly asymmetric genetic architecture, where most of the genetic variation is concentrated on a small number of loci. We show that the evolution of genetic architecture can be understood in terms of the ecological niches created by competition. The phenotypic distribution of a population with an adapted genetic architecture closely matches this niche structure. Thus, evolution of the genetic architecture seems to be a plausible way for populations to adapt to regimes of frequency-dependent disruptive selection. As such, it should be seen as a potential evolutionary pathway to discrete polymorphisms and as a potential alternative to other evolutionary responses, such as the evolution of sexual dimorphism or assortative mating.
Serotonin2C receptors modulate dopamine transmission in the nucleus accumbens independently of dopamine release: behavioral, neurochemical and molecular studies with cocaine

In keeping with its ability to control the mesoaccumbens dopamine (DA) pathway, the serotonin2C receptor (5‐HT2CR) plays a key role in mediating the behavioral and neurochemical effects of drugs of abuse. Studies assessing the influence of 5‐HT2CR agonists on cocaine‐induced responses have suggested that 5‐HT2CRs can modulate mesoaccumbens DA pathway activity independently of accumbal DA release, thereby controlling DA transmission in the nucleus accumbens (NAc). In the present study, we assessed this hypothesis by studying the influence of the 5‐HT2CR agonist Ro 60‐0175 on cocaine‐induced behavioral, neurochemical and molecular responses. The i.p. administration of 1 mg/kg Ro 60‐0175 inhibited hyperlocomotion induced by cocaine (15 mg/kg, i.p.), had no effect on cocaine‐induced DA outflow in the shell, and increased it in the core subregion of the NAc. Furthermore, Ro 60‐0175 inhibited the late‐onset locomotion induced by the subcutaneous administration of the DA‐D2R agonist quinpirole (0.5 mg/kg), as well as cocaine‐induced increase in c‐Fos immunoreactivity in NAc subregions. Finally, Ro 60‐0175 inhibited cocaine‐induced phosphorylation of the DA and c‐AMP regulated phosphoprotein of Mr 32 kDa (DARPP‐32) at threonine residues in the NAc core, this effect being reversed by the selective 5‐HT2CR antagonist SB 242084 (0.5 mg/kg, i.p.). Altogether, these findings demonstrate that 5‐HT2CRs are capable of modulating mesoaccumbens DA pathway activity at post‐synaptic level by specifically controlling DA signaling in the NAc core subregion. In keeping with the tight relationship between locomotor activity and NAc DA function, this interaction could participate in the inhibitory control of cocaine‐induced locomotor activity.
Antigenic characterization of endothelial cell‐derived microparticles and their detection ex vivo

Summary. Background: Endothelial activation and dysfunction are associated with several diseases. However, hardly any specific markers are available. Microparticles (MP) from endothelial cells (EC; EMP) were reported in patient groups and healthy individuals. The antibodies used to detect EMP, however, were mainly directed against antigens without EC specificity. Objectives: We evaluated the antigens on EC and EMP to establish proper markers for EMP detection. Methods: EMP were isolated from supernatants of resting and interleukin (IL)‐1α activated human umbilical vein EC (HUVEC; n = 3; 0–72 h), stained with annexin V and monoclonal antibodies, and analyzed by flow cytometry. Human platelet‐MP (PMP), the main MP population in plasma, were prepared in vitro. EMP and PMP were studied in plasma from systemic lupus erythematosus (SLE) patients (n = 11) and healthy individuals (n = 10). Results: Platelet–endothelial cell adhesion molecule‐1 (PECAM‐1), αν and β3 were constitutively exposed on HUVEC, but (almost) absent on EMP (<15% positive for αν and β3), or only exposed on a subpopulation (PECAM‐1; 30–60%). Activated HUVEC (>80%) and (subpopulations of) EMP exposed E‐selectin and tissue factor. PMP strongly exposed PECAM‐1, β3, and glycoprotein (GP)Ib (CD42b), but not αν or E‐selectin. GPIb and P‐selectin (CD62P) were absent on EMP. Plasma samples contained 0.5% MP staining for E‐selectin and/or αν. Plasma from one SLE patient contained E‐selectin exposing MP (21%), but little αν‐positive MP. Conclusions: EC release EMP in vitro. The antigenic phenotype of EMP released from resting and IL‐1α‐stimulated EC differs among each other as well as from resting and stimulated EC, respectively. E‐selectin exposed on IL‐1α‐stimulated EC is a valid marker for EMP detection ex vivo to establish endothelial cell activation.
RivR Is a Negative Regulator of Virulence Factor Expression in Group A Streptococcus

ABSTRACT The bacterial pathogen group A Streptococcus (GAS) causes human diseases ranging from self-limiting pharyngitis (also known as strep throat) to severely invasive necrotizing fasciitis (also known as the flesh-eating syndrome). To control virulence factor expression, GAS utilizes both protein- and RNA-based mechanisms of regulation. Here we report that the transcription factor RivR (RofA-like protein IV) negatively regulates the abundance of mRNAs encoding the hyaluronic acid capsule biosynthesis proteins (hasABC; ∼7-fold) and the protein G-related α2-macroglobulin-binding protein (grab; ∼29-fold). Our data differ significantly from those of a previous study of the RivR regulon. Given that grab and hasABC are also negatively regulated by the two-component system CovR/S (control of virulence), we tested whether RivR functions through CovR/S. A comparison of riv and cov single and double mutant strains showed that RivR requires CovR activity for grab and hasABC regulation. Analysis of the upstream region of rivR identified a novel promoter the deletion of which reduced rivR mRNA abundance by 70%. A rivR mutant strain had a reduced ability to adhere to human keratinocytes relative to that of the parental and complemented strains, a phenotype that was abolished upon GAS pretreatment with hyaluronidase, highlighting the importance of capsule regulation by RivR during colonization. The rivR mutant strain was also attenuated for virulence in a murine model of bacteremia infection. Thus, we identify RivR as an important regulator of GAS virulence and provide new insight into the regulatory networks controlling virulence factor production in this pathogen.
Tadalafil rehabilitation therapy preserves penile size after bilateral nerve sparing radical retropubic prostatectomy.

OBJECTIVE To evaluate the change in penile size r bilateral nerve sparing retropubic radical prostatectomy (BNSRRP) and possible effect of Tadalafil. MATERIALS AND METHODS A total of 65 patients underwent BNSRRP and they were evaluated prospectively for a whole year of follow-up. The patients were randomized to control without rehabilitation (Group 1) or Tadalafil rehabilitation group (Group 2). The patients were evaluated at months 3, 6 and 12 postoperatively for erectile function, penile measurements (flaccid penile length, penile length at maximum erection, penile circumference at flaccid status, and penile circumference at maximum erection), penile abnormalities and general health status. Statistical analysis was performed by Chi-Square test and significance was defined as p value < 0.05. RESULTS In Group 1 there was significant decrease in penile measurements at month 3 compared to preoperative measurements. There was decrease in all parameters at month 6 compared to month 3 but only the decrease in penile length at maximum erection was significant. There were no significant differences between postoperative months 6 and 12 for all measurements. In Group 2 there was a tendency to decrease in all measurements at month 3 compared to baseline. There was no significant difference for penile measurements between postoperative 3rd and 6th months and between 6th month and the first year. CONCLUSION Although further large sampled trials are needed to describe the possible positive effect of tadalafil or other PDE5-I 's on penile size after BNSRRP, tadalafil rehabilitation is effective in preserving penile size especially in the early postoperative period after BNSRRP.
ASSESSMENT GROWTH LIMITS AND MOBILITY: EVIDENCE FROM HOME SALE DATA IN DETROIT, MICHIGAN

In 1994 the State of Michigan imposed a limit on the growth of property values for tax purposes. The assessment growth cap resulted in the emergence of a differential in effective tax rates between new and long-time property owners. This article examines the degree to which this differential creates a lock-in effect. Using parcel-level data from the City of Detroit, we find that homeowners who have lower effective tax rates are less likely to sell their properties; the average duration of property ownership is 7.5 years longer as a result of the assessment growth cap.
Cost-effectiveness of fall prevention programs based on home visits for seniors aged over 65 years: a systematic review

Abstract Background: Preventive home visits (PHVs) are considered a promising intervention to improve health and independent functioning of the elderly whilst reducing health care costs. This systematic review focuses on cost-effectiveness of PHVs, analyzing randomized controlled trials evaluating incremental cost-effectiveness ratios in fall prevention interventions. Methods: Based on an online search (PubMed) and bibliographic findings in the eligible articles, five studies providing relevant information were reviewed. Results: While three studies indicate cost-effectiveness, one delivered no statistically significant results, and one proved cost-effectiveness only for a subgroup of the study sample. Conclusions: Cost-effectiveness of PHVs appears to depend on careful adaptation of particular measures, for certain settings in special environments for designated patients and disease patterns, on a case-by-case basis. Starting points for further research are the components of the economic evaluation, the setting, personnel and measures of the intervention, as well as the careful selection and analysis of the study sample and its subgroups. A uniform follow-up time, standardized cost measurement as well as the use of standardized denominators like quality adjusted life years (based on the EQ-5D questionnaire) could build a foundation for comparable results.
Alcohol sensitizes cerebral responses to the odors of alcoholic drinks: an fMRI study.

BACKGROUND Small, priming doses of alcohol enhance desire to drink, and thus play a role in the loss of control of alcohol consumption. Using functional magnetic resonance imaging (fMRI), we previously showed that alcoholic drink odors (AO; subjects' drinks of choice) induce greater nucleus accumbens (NAc) activity than non-appetitive odors (NApO; grass, leather) in subjects at risk for alcoholism. Here we hypothesized that priming exposure to alcohol would enhance responses to AO in the NAc and orbitofrontal cortex in comparison to NApO (grass, leather) and to the appetitive control odors (ApCO) of chocolate and grape. METHODS Ten hazardous drinkers (mean age = 22.7; SD = 2.9, average drinks per drinking day = 5.9, SD = 2.3; drinking days/90 days = 50.4, SD = 13.7) were scanned on a 1.5 T GE Signa MR scanner during intravenous infusion of lactated Ringer's or 6% ethanol in lactated Ringer's that was pharmacokinetically modeled to achieve a constant breath alcohol concentration (BrAC) of 50 mg% throughout imaging. During scanning, subjects sniffed AO, NApO, and ApCO. RESULTS Alcohol infusion enhanced the contrast between AO and NApO in the NAc, and in orbitofrontal, medial frontal, and precuneus/posterior cingulate regions. The contrast between AO and appetitive control odors (ApCO; chocolate and grape) was similarly larger in the orbital, medial frontal, precuneus, and posterior cingulate/retrosplenial areas, with the most robust finding being a potentiated response in the posterior cingulate/retrosplenial area. The orbital region is similar to an area previously shown to manifest satiety-related decreases in activity induced by food cues. CONCLUSIONS The results suggest that priming exposure to alcohol renders a limbic network more responsive to alcohol cues, potentially enhancing desire to drink.
Identity and the Theory of Planned Behavior: Predicting Maintenance of Volunteering After Three Years

ABSTRACT Is identity an important predictor of social behavior? The present longitudinal study is focused on identity in order to understand why people continue to volunteer over an extended period of time. The theory of planned behavior and the role identity model of volunteering are used as theoretical framework. Two hundred thirty Italian volunteers were sampled and followed for 3 years. We analyzed functions of role identity as a volunteer. Results showed a significant impact of role identity in predicting volunteer performance after 3 years, mediated through behavioral intentions. Role identity fully mediated the relationships between behavioral intention and attitude, social norms, past behavior and parental modelling.
Ischaemic stroke: a thrombo‐inflammatory disease?

Abstract Ischaemic stroke is a leading cause of death and disability worldwide. The complex cellular interactions leading from thromboembolic vessel occlusion to infarct development within the brain parenchyma in acute stroke are poorly understood, which translates into only one approved effective treatment, thrombolysis. Importantly, however, patients can develop progressive stroke despite reperfusion of previously occluded major intracranial arteries, a process referred to as ‘reperfusion injury’ which can be reproduced in the mouse model of transient middle cerebral artery occlusion (tMCAO). Although pathological platelet and coagulant activity have long been recognized to be involved in the initiation of ischaemic stroke, their contribution to infarct maturation remained elusive. Experimental evidence now suggests that early platelet adhesion/activation mechanisms involving the von Willebrand factor (vWF) receptor glycoprotein (GP) Ib, its ligand vWF, and the collagen receptor GPVI are critical pathogenic factors in infarct development following tMCAO, whereas platelet aggregation through GPIIb/IIIa is not. Further experimental work indicates that these pathways in conjunction with coagulation factor XII (FXII)‐driven processes orchestrate a ‘thrombo‐inflammatory’ cascade in acute stroke that results in infarct growth. This review summarizes these recent developments and briefly discusses their potential clinical impact.
Validity and reliability of the 13C-methionine breath test for the detection of moderate hyperhomocysteinemia in Mexican adults

Abstract Background: Hyperhomocysteinemia (Hhcy) is considered an independent risk factor for vascular diseases and, more recently, for dementia. The methionine loading test (MLT) is useful for diagnosing additional subjects with moderate Hhcy. However, it is a complex and time-consuming procedure. A noninvasive test for the diagnosis of moderate Hhcy is desirable. Methods: The study protocol consisted of three consecutive visits. During the first visit, we performed an MLT to characterize the Hhcy status of 75 healthy adult subjects. For the breath test protocol, we selected a subsample and assigned to the control group 17 subjects with fasting and post-loading homocysteine (Hcy) ≤12 and <42.3 μmol/L, respectively, and to the Hhcy group 16 subjects with fasting Hcy ≤12 and >42.3 μmol/L after loading. Selected subjects were requested to have a second visit to perform a breath test within 1–4 weeks following the MLT test and received an oral dose of 2.5 mg/kg of 1-13C-methionine dissolved in water. Breath samples were collected at basal, 20, 40, 60, 80, 100 and 120 min (test 1). The same procedure was repeated within 1 week (test 2). Results: MLT was useful for diagnosing almost twice the number of individuals with Hhcy (24%) in comparison with the fasting determination alone (13.3%). The 13C-methionine breath test reported a sensitivity of 81.3% and a specificity of 64.7% against the MLT. The coefficient of variation between breath test 1 and breath test 2 was 9.0±5.4%. Conclusions: The 13C-methionine breath test is a valid and reliable method for identifying subjects with moderate Hhcy.
Intra-articular injection of hyaluronic acid is not superior to saline solution injection for ankle arthritis: a randomized, double-blind, placebo-controlled study.

BACKGROUND Intra-articular injections of hyaluronic acid are potentially useful to treat ankle osteoarthritis, yet their effectiveness has not been proven. Both single and multiple-dose treatments for ankle arthritis with use of various hyaluronic acid products have been recommended, but few high-quality studies have been published. The aim of this study was to compare the effectiveness of a single intra-articular injection of hyaluronic acid with a single intra-articular injection of normal saline solution (placebo) for osteoarthritis of the ankle. METHODS Sixty-four patients with ankle osteoarthritis who met all study criteria were randomly assigned to a single intra-articular injection of 2.5 mL of low-molecular-weight, non-cross-linked hyaluronic acid or a single intra-articular injection of 2.5 mL of normal saline solution. The primary outcome measure was the change from baseline in the American Orthopaedic Foot & Ankle Society (AOFAS) clinical rating score at the six-week and twelve-week follow-up examination. Secondary outcome measures included the Ankle Osteoarthritis Scale score and patient-reported pain with use of a visual analog pain scale. RESULTS Of the sixty-four patients randomized and treated, eight patients withdrew, leaving fifty-six patients who completed the entire study. There was one mild adverse event (1.6%) among the sixty-four patients. At six weeks and twelve weeks, the mean AOFAS scores in the hyaluronic acid group had improved from baseline by 4.9 and 4.9 points, respectively, whereas the mean AOFAS scores in the placebo group initially worsened by 0.4 point at six weeks and then improved by 5.4 points at twelve weeks. While the change at twelve weeks from baseline was substantial for both groups, the between-group differences were not significant. CONCLUSIONS We found that a single intra-articular injection of low-molecular-weight, non-cross-linked hyaluronic acid is not demonstrably superior to a single intra-articular injection of saline solution for the treatment of osteoarthritis of the ankle.
Prevalence and factors predictive of long-acting reversible contraceptive use in a tertiary hospital in urban Ghana

Abstract Objective To determine the prevalence, socio-demographic and reproductive factors associated with long-acting reversible contraceptive (LARC) use among clients resorting to reversible birth control methods in a tertiary hospital in Ghana. Methods Retrospective review of records of clients who opted for reversible family planning (FP) methods at Komfo Anokye Teaching Hospital, Kumasi, Ghana, from 1 July 2003 to 30 June 2008. We recorded data on their contraceptive history, and socio-demographic- and reproductive characteristics. Categorical variables were compared using the χ2 test and factors associated with LARC uptake examined by binomial regression with a log-link function to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results Of 5946 clients who opted for reversible contraception, 71% chose LARCs, and the remaining 29% chose shorter-acting contraceptives. LARCs were employed mainly by women with more living children (p trend < 0.001) who had previously used LARCs (adjusted RR: 1.49; 95% CI: 1.39–1.60). Over half of non-contraceptive users started with LARCs while 27% of women switched from shorter-acting contraceptives to LARCs. Conclusion The prevalence of LARC uptake was much higher than the national average. Significant factors associated with current LARC use were the number of surviving children and previous LARC use.
Gaze + pinch interaction in virtual reality

Virtual reality affords experimentation with human abilities beyond what's possible in the real world, toward novel senses of interaction. In many interactions, the eyes naturally point at objects of interest while the hands skilfully manipulate in 3D space. We explore a particular combination for virtual reality, the Gaze + Pinch interaction technique. It integrates eye gaze to select targets, and indirect freehand gestures to manipulate them. This keeps the gesture use intuitive like direct physical manipulation, but the gesture's effect can be applied to any object the user looks at --- whether located near or far. In this paper, we describe novel interaction concepts and an experimental system prototype that bring together interaction technique variants, menu interfaces, and applications into one unified virtual experience. Proof-of-concept application examples were developed and informally tested, such as 3D manipulation, scene navigation, and image zooming, illustrating a range of advanced interaction capabilities on targets at any distance, without relying on extra controller devices.
Overcoming recruitment challenges in construction safety intervention research.

BACKGROUND Recruiting workers in small construction companies and securing their participation in voluntary safety programs or safety research poses unique challenges. Worker turnover and worksite changes contribute to difficulties in locating and enrolling participants. Economic pressures and time demands potentially threaten ongoing participation. METHODS Six simulation exercises designed to reduce back and fall injuries in small construction companies were developed based on data from focus groups of workers and company owners. Working with a workers' compensation insurer, we had access to owner-operators of general, heavy, and special trade construction companies reporting less than $10,000 in payroll expenses. Recruitment methods included a participation incentive, mailed invitations followed by phone contacts, and follow-up reminders. RESULTS Despite using recruitment methods recommended in the literature, participation rates were low over a 2-year intervention period. Because of these difficulties, factors affecting participation or nonparticipation became an additional research focus. Owners' perceptions of already having a good safety record and of the time demands of participation were the most commonly cited reasons for not participating. CONCLUSIONS Literature on recruitment emphasizes processes and procedures under investigator control rather than understanding potential participants' judgments about the adequacy of their existing practices and the potential benefits of intervention participation relative to potential time and productivity trade-offs. Greater attention to such judgments may enhance recruitment and participation in under-studied and difficult to access populations.