Miracle-dz/UniFAR-FTUs huggingface dataset:
A study of linkage and association of body mass index in the old order Amish

Obesity is thought to have a genetic component with the estimates of heritability ranging from 0.25–0.40. As part of an ongoing study of obesity in the Old Order Amish, seven two‐ and three‐generation families (157 individuals) were assessed for 21 traits related to obesity, including body mass index (BMI) and BMI‐percentile (a standardized distribution of BMI adjusted for age and sex). Genotyping was performed using a panel of 384 short‐tandem repeat markers. In this sample, the estimates of heritability ranged from 0.16–0.31 for BMI and from 0.40–0.52 for BMI‐percentile. Model‐independent linkage analysis identified candidate regions on chromosomes 1, 5, 7, 8, and 11. Given that several markers on 7q were significant for both BMI and BMI‐percentile (P ≤ 0.001) and that the structural locus for leptin was located on 7q, this region was considered to be the primary candidate region. Subsequent typing of additional flanking markers on 7q corroborated the original findings. Tests of intrafamilial association for alleles at markers in this candidate region were significant at similar levels. Although there is some evidence for linkage and association in the region containing leptin, there appears to be stronger evidence for linkage (P ≤ 0.001) and association (P ≤ 0.00001) with BMI in a region 10–15 cM further downstream of leptin, flanked by markers D7S1804 and D7S3070 with peak values from D7S495–D7S1798. Evidence from linkage and association studies suggests that this region (D7S1804–D7S3070) may be responsible, at least in part, for variation in BMI and BMI‐percentile in the Old Order Amish. Published 2003 Wiley‐Liss, Inc.
Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation, characterization, plasma, and kidney pharmacokinetics

Abstract The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6 ± 5.95 nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71 ± 3.02%, and the drug loading was 1.56 ± 0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUCkidney/AUCplasma = 0.586 ± 0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.
Evaluation of molecular typing methods for identification of outbreak‐associated Neisseria meningitidis isolates

It is essential in an outbreak investigation that strain characterization of Neisseria meningitidis is performed in a rapid and accurate manner. This study evaluated two new molecular typing methods, multiple‐locus variable number tandem repeat analysis (MLVA) and repetitive sequence‐based PCR (rep‐PCR) (DiversiLab; bioMérieux) and compared them with current recommended methodologies. This retrospective study included 36 invasive N. meningitidis serogroup C isolates collected in Sweden 2001 through 2009 and previously subjected to outbreak investigation. All strains were typed with highly variable‐MLVA (HV‐MLVA) and rep‐PCR. The isolates were further characterized by multilocus sequence typing (MLST) and sequencing of the fetA, fHbp, penA, porA and porB genes. The results showed that HV‐MLVA had the highest index of diversity (0.99) and rep‐PCR had the highest congruence (40%) with the currently recommended typing methods. The HV‐MLVA correlated best to the spatiotemporal connections and had the overall highest Adjusted Wallace coefficients, suggesting that HV‐MLVA can predict the results of the other typing methods in the study. We therefore suggest that after initial confirmation of species, serogroup and genosubtype, HV‐MLVA should be used as the most discriminatory method for first hand investigation of N. meningitidis serogroup C isolates.
Administration of Liposomal Agents and Blood Clearance Capacity of the Mononuclear Phagocyte System

ABSTRACT As liposomes are cleared from the circulation to a substantial extent by the phagocytic cells of the mononuclear phagocyte system (MPS), there is a question whether administration of liposome-based therapeutic agents interferes with clearance of infectious organisms by the MPS from blood. In the present study, at first the effect of administration of three types of empty liposomes (devoid of drug), differing in blood residence time, on carbon clearance and bacterial clearance from blood was studied with mice. Classical liposomes (LIP A) and placebo liposomes with lipid composition as in AmBisome (LIP B) or as in Doxil (LIP C) were used. Liposomes were administered intravenously as a single dose. Second, the effect of multiple-dose administration of AmBisome on bacterial blood clearance was studied with rats. AmBisome was administered with two different dosage schedules. The blood clearance capacity of the MPS was monitored at different time points after the last liposome injection. It was shown that the carbon blood clearance capacity of the MPS was impaired only at a high lipid dose of empty classical liposomes. The bacterial blood clearance capacity was never impaired, not even after prolonged treatment with AmBisome administered in a clinically relevant regimen.
Pulmonary arterial hypoxic contraction: signal transduction.

The response of isolated rat pulmonary arteries to acute hypoxia has previously been reported to be biphasic, consisting of an initial rapid contraction of short duration, followed by partial relaxation (phase 1) and then a second slowly developed but sustained contraction (phase 2). The purpose of this study was to determine the following: 1) whether products from the endothelium might be required, 2) whether extra- and/or intracellular calcium or protein kinase C might be second messengers in mediating the pulmonary arterial hypoxic contraction, and 3) whether or not guanosine 3',5'-cyclic monophosphate (cGMP), endothelium-derived relaxing factor (EDRF), prostaglandin I2 (PGI2) or A2 adenosine receptor activation is involved in phase 1 relaxation. Neither Ca(2+)-free media nor verapamil (a Ca2+ channel blocker) altered the phase 1 contraction, but the phase 2 contraction was abolished by either of these treatments. Ryanodine (a sarcoplasmic reticulum Ca2+ depleter) had no effect on phase 1 contraction. H-7 (a PKC inhibitor) inhibited the phase 2 contraction, whereas it had no effect on phase 1 contraction. Removal of the endothelium abolished phase 1 contraction in either Ca(2+)-free media or normal Ca2+ media but did not alter phase 2 contraction or phase 1 relaxation. Neither methylene blue (guanylate cyclase inhibitor), N omega-nitro-L-arginine, (EDRF blocker), acetylsalicylic acid (cyclooxygenase inhibitor), xanthine amino congener (adenosine receptor blocker), nor glybenclamide blocked the phase 1 relaxation. (ABSTRACT TRUNCATED AT 250 WORDS)
Mapping circular economy activities in the European Union: Patterns of implementation and their correlates in small and medium‐sized enterprises

With the European Commission looking for ways to incentivize the adoption of circular economy (CE) activities by small and medium‐sized enterprises (SMEs) in the European Union (EU), further insights into the implementation of CE activities across member states are needed. We analyse a European Commission survey conducted in 2016 among approximately 11,000 firms in EU‐28 member states in order to throw light on the conditions in which SMEs engage in five specific CE activities. In contrast to previous studies arguing that CE activities are independent of each other, we present novel findings demonstrating that seven patterns of engagement in CE can be identified in which activities are systematically interdependent. Further, we show that these patterns are associated with the organizational properties of SMEs and are differentially distributed among EU member states and industrial sectors. The interdependency of activities forms a hierarchy in which waste minimization is the most likely activity to be implemented in SMEs, followed, in descending order of likelihood, by replanning of energy use, redesigning products and services, and finally using renewable energy and replanning water usage. The findings have theoretical, managerial, and policy implications for the adoption of interdependent CE activities.
Hepatitis B Virus X Protein Stimulates Viral Genome Replication via a DDB1-Dependent Pathway Distinct from That Leading to Cell Death

ABSTRACT The hepatitis B virus (HBV) X protein (HBx) is essential for virus infection and has been implicated in the development of liver cancer associated with chronic infection. HBx can interact with a number of cellular proteins, and in cell culture, it exhibits pleiotropic activities, among which is its ability to interfere with cell viability and stimulate HBV replication. Previous work has demonstrated that HBx affects cell viability by a mechanism that requires its binding to DDB1, a highly conserved protein implicated in DNA repair and cell cycle regulation. We now show that an interaction with DDB1 is also needed for HBx to stimulate HBV genome replication. Thus, HBx point mutants defective for DDB1 binding fail to complement the low level of replication of an HBx-deficient HBV genome when provided in trans, and one such mutant regains activity when directly fused to DDB1. Furthermore, DDB1 depletion by RNA interference specifically compromises replication of wild-type HBV, indicating that HBx produced from the viral genome also functions in a DDB1-dependent fashion. We also show that HBx in association with DDB1 acts in the nucleus and stimulates HBV replication mainly by enhancing viral mRNA levels, regardless of whether the protein is expressed from the HBV genome itself or supplied in trans. Interestingly, whereas HBx induces cell death in both HepG2 and Huh-7 hepatoma cell lines, it enhances HBV replication only in HepG2 cells, suggesting that the two activities involve distinct DDB1-dependent pathways.
Utility of Immunohistochemistry in Separating Thymic Neoplasms From Germ Cell Tumors and Metastatic Lung Cancer Involving the Anterior Mediastinum

A variety of primary and metastatic neoplasms can involve the anterior mediastinum and have similar radiographic or histologic appearances. We report an immunohistochemical (IHC) panel that includes CD5, placental-like alkaline phosphatase (PLAP), thyroid transcription factor 1 (TTF-1), cytokeratin (CK) 7, CK20, CK5/6, and CD57 for the separation of thymic neoplasms from germ cell tumors (GCTs) and metastatic lung malignancies. One hundred cases representing different types of neoplasms involving the anterior mediastinum were retrieved and consisted of 20 pulmonary adenocarcinomas (PAs), 20 pulmonary large cell carcinomas (PLCs), 20 pulmonary squamous cell carcinomas (PSCCs), 20 thymomas (Ths), 10 invasive thymomas (IThs), and 10 thymic carcinomas (TCs). Fifteen cases of GCTs were also included in the study. CD5 was positive in 17 of 20 PAs, 11 of 20 PLCs, 2 of 15 GCTs, and 9 of 10 TCs. PLAP was positive in 5 of 20 PAs, 2 of 20 PLCs, 1 of 20 PSCCs, and 11 of 15 GCTs. TTF-1 was positive in 18 of 20 PAs, 10 of 20 PLCs, and 2 of 20 PSCCs. CK7 was positive in 20 of 20 PAs, 15 of 20 PLCs, 8 of 20 PSCCs, 5 of 15 GCTs, 11 of 20 Ths, 7 of 10 IThs, and 4 of 10 TCs. CK20 was positive only in 2 of 20 PAs. CK5/6 was positive in all cases of PSCC, Th, ITh, and TC, in 9 of 20 PLCs, and 1 of 15 GCTs. CD57 was positive in 9 of 20 PAs, 3 of 20 PLCs, 8 of 15 GCTs, 13 of 20 Ths, and 6 of 10 IThs. In conclusion, CD5 had low specificity for TC (60%) because it also stained 85% of PA and 55% of PLC. CK5/6 was a sensitive but not a specific IHC marker for the epithelial component of thymic neoplasms (100%); TTF-1 had a good sensitivity (90%) and excellent specificity (100%) for distinguishing PA from thymic neoplasms. An IHC panel consisting of CD5, CK5/6, PLAP, TTF-1, and CD57 is useful for the separation of thymic neoplasms from other epithelial malignancies involving the mediastinum.
THE PARADOX OF THE FLIPPED CLASSROOM: ONE METHOD, MANY INTENTIONS

The Flipped Classroom is a teaching model where content attainment is shifted forward to outside of class, to be followed up by the teacher in class. In Sweden this way of teaching has become very popular during recent years. But what is gained by this way of teaching? Research on the Flipped Classroom in the context of the Swedish High School system is close to non-existent; why studies within this field are of great importance. In order to find appropriate informants, an electronic survey was constructed. Informants matching the selection criteria were then selected for qualitative interviews. In total nine informants agreed to participate in interviews (semi-structured) to describe their experiences from flipping their own classrooms. The informants reported that the transition from more conventional ways of teaching to using the Flipped Classroom entailed major changes. The informants pointed out that the process of moving away from the more conventional way of teaching improved their teaching. All of the informants expressed they all used the Flipped Classroom methodology but they all did it with different goals in mind and their approach varied a lot. By using the same terminology, it might seem that they worked with the Flipped Classroom in similar ways, but the results show they did not. Herein lies the problem: Teachers say they flip their classrooms, which they do, but they do not share the same goals or approaches, just the term: The Flipped Classroom. Keywords: flipped classroom, flipped education, qualitative interviews, teaching methodology.
Functional gastrointestinal disorders as a public health problem

Summary The functional gastrointestinal disorders (FGIDs) are a heterogeneous group of chronic conditions that are considered to be important to public health because they are remarkably common, can be disabling, and induce a major social and economic burden. Despite the Rome consensus process, the line defining true abnormality from health is as yet imprecise. Furthermore, the concept that the FGIDs have no pathological or biochemical correlates is starting to unravel, and some candidate morphometric abnormalities (e.g. duodenal eosinophilia, colonic mastocytosis) have been documented. The quality of care that patients with FGIDs receive is not well understood, despite the high volume of patients seen in primary and specialty care. There are a remarkable number of symptom‐based and disease‐based co‐morbidities that appear to be more common in those with FGIDs that are not alone explained by coexistent somatization. Whether there is any means of preventing the development of FGIDs post‐infection is untested but has vast public health implications. Defining disease severity remains key to better understanding the public health impact of FGIDs; severity is probably influenced by the intestinal and extra‐intestinal symptom burden, psychological distress and the impact on quality of life, but how these factors interact remains uncertain. An important future research direction must be to quantify at what risk level it is reasonable to prescribe a medication that may be dangerous, and stratify which subsets of patients with FGIDs would qualify for such an approach using objective well validated tools (e.g. based on accurately defining gradations of severity of disease). Finally, there are some reasons to suspect that there may be an increase in mortality in FGID sufferers; for example, unnecessary surgery or invasive testing has a small but not zero associated mortality, and this should be a factor in view of the high prevalence of disease.
Skin conductance conditioning to potentially phobic stimuli as a function of interstimulus interval and delay versus trace paradigm.

Because prepared learning has been defined in terms of response acquisition in spite of degraded input, it was expected that differences in resistance to extinction between skin conductance responses conditioned to potentially phobic and neutral stimuli would increase with increased interstimulus interval (ISI) and be larger with a trace than with a delay conditioning paradigm. Twelve groups with 10 subjects each were observed in a differential conditioning experiment manipulating ISI (2, 8, or 16 sec), paradigm (delay versus trace), and fear-relevance of the conditioned stimulus (potentially phobic versus neutral). The results showed highly reliable resistance to extinction of first-interval anticipatory responses to phobic stimuli, and no resistance to extinction of the corresponding responses to the neutral stimuli. This difference did not interact either with the ISI or the paradigm factor. Thus, although underscoring the reliability of the difference in conditioning to potentially phobic and neutral stimuli, the results did not support the specific hypothesis of conditioning to phobic stimuli as being less dependent on the ISI parameters than conditioning to neutral stimuli.
Personalizing Intraocular Pressure: Target Intraocular Pressure in the Setting of 24-Hour Intraocular Pressure Monitoring

AbstractDetermining target intraocular pressure (IOP) in glaucoma patients is multifaceted, requiring attention to many different factors such as glaucoma type, severity of disease, age, race, family history, corneal thickness and hysteresis, and initial IOP. Even with all these variables accounted for, there are still patients who have progression of the disease despite achieving target IOP. Intraocular pressure variability has been identified as a potential independent risk factor for glaucoma progression but is currently difficult to quantify in individual patients. New technologies enabling measurement of both diurnal and nocturnal IOP may necessitate modifying our concept of target pressure.
Non‐selective vs. selective beta‐blocker treatment and the risk of thrombo‐embolic events in patients with heart failure

Heart failure (HF) is associated with a prothrombotic state, resulting in an increased risk for thrombo‐embolic events. Studies suggest a reduced prothrombotic state when non‐selective beta‐blockers relative to selective beta‐blockers are given. We studied the influence of non‐selective beta‐blockers compared with selective beta‐blockers on the occurrence of arterial and venous thrombo‐embolic events in patients with HF.
Consumer satisfaction with involvement in drug research: a social validity study.

OBJECTIVE To assess the social importance and personal benefit attached to involvement in drug research for participating families. METHOD Parents of children with mental retardation or borderline IQ who took part in two drug studies were surveyed by mail 4 weeks after their involvement. The questionnaire addressed the acceptability of study procedures and satisfaction with study outcomes ("social validity"). RESULTS Forty (63.5%) of 63 families responded to the survey. In all, 83% felt that their questions were satisfactorily answered regarding the role of medication for their children, and 88% were satisfied with the individual conclusions reached regarding pharmacotherapy for their children. Virtually all parents believed that the study assessments used were important, and 88% indicated that they would join the study again if faced with the same choices. CONCLUSIONS These parents appear to have found the research experience to be of practical benefit to them, and they were generally positive about their experiences. As this seems to be the only published study of the social or perceived validity of drug research, more surveys of this type are needed to assess consumer reactions to a broader array of research experiences.
Macrophage activation is associated with poorer long‐term outcomes in renal transplant patients

Grebe SO, Kuhlmann U, Fogl D, Luyckx VA, Mueller TF. Macrophage activation is associated with poorer long‐term outcomes in renal transplant patients. Clin Transplant 2011: 25: 744–754. © 2010 John Wiley & Sons A/S.
Wound-Inducible Biosynthesis of Phytoalexin Hydroxycinnamic Acid Amides of Tyramine in Tryptophan and Tyrosine Decarboxylase Transgenic Tobacco Lines1

The wound-activated biosynthesis of phytoalexin hydroxycinnamic acid amides of tyramine was compared in untransformed and transgenic tobacco (Nicotiana tabacum) lines that express tryptophan decarboxylase (TDC), tyrosine decarboxylase (TYDC), or both activities. Transgenic in vitro-grown tobacco lines expressing TDC activity accumulated high levels of tryptamine but not hydroxycinnamic amides of tryptamine. In contrast, transgenic tobacco lines expressing TYDC accumulated tyramine as well as p-coumaroyltyramine and feruloyltyramine. The MeOH-soluble and cell wall fractions showed higher concentrations of wound-inducible p-coumaroyltyramine and feruloyltyramine, especially at and around wound sites, in TYDC and TDC ×TYDC tobacco lines compared to wild-type or TDC lines. All the enzymes involved in the biosynthesis of hydroxycinnamic acid amides of tyramine were found to be similarly wound inducible in all tobacco genotypes investigated. These results provide experimental evidence that, under some circumstances, TYDC activity can exert a rate-limiting control over the carbon flux allocated to the biosynthesis of hydroxycinnamic acid amides of tyramine.
The influence of mean climate trends and climate variance on beaver survival and recruitment dynamics

Ecologists are increasingly aware of the importance of environmental variability in natural systems. Climate change is affecting both the mean and the variability in weather and, in particular, the effect of changes in variability is poorly understood. Organisms are subject to selection imposed by both the mean and the range of environmental variation experienced by their ancestors. Changes in the variability in a critical environmental factor may therefore have consequences for vital rates and population dynamics. Here, we examine ≥90‐year trends in different components of climate (precipitation mean and coefficient of variation (CV); temperature mean, seasonal amplitude and residual variance) and consider the effects of these components on survival and recruitment in a population of Eurasian beavers (n = 242) over 13 recent years. Within climatic data, no trends in precipitation were detected, but trends in all components of temperature were observed, with mean and residual variance increasing and seasonal amplitude decreasing over time. A higher survival rate was linked (in order of influence based on Akaike weights) to lower precipitation CV (kits, juveniles and dominant adults), lower residual variance of temperature (dominant adults) and lower mean precipitation (kits and juveniles). No significant effects were found on the survival of nondominant adults, although the sample size for this category was low. Greater recruitment was linked (in order of influence) to higher seasonal amplitude of temperature, lower mean precipitation, lower residual variance in temperature and higher precipitation CV. Both climate means and variance, thus proved significant to population dynamics; although, overall, components describing variance were more influential than those describing mean values. That environmental variation proves significant to a generalist, wide‐ranging species, at the slow end of the slow‐fast continuum of life histories, has broad implications for population regulation and the evolution of life histories.