Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized Study of Persistent Atrial Fibrillation Ablation: Ablate in Sinus Rhythm Versus Ablate Complex-Fractionated Atrial Electrograms in Atrial Fibrillation

Background—Achieving long-term successful outcomes with ablation of persistent atrial fibrillation (AF) remains a clinical and procedural challenge. We aimed to assess 2 ablation strategies for persistent AF: pulmonary vein antral isolation (PVAI) in sinus rhythm after direct current cardioversion versus PVAI and ablation targeting complex-fractionated atrial electrograms while in AF. Methods and Results—Between June 2009 and July 2013, patients with continuous persistent AF for ≥3 months were prospectively randomized to either direct current cardioversion before PVAI and posterior wall/septum ablation while in sinus rhythm (group 1), versus same ablation in group 1 in addition to complex-fractionated atrial electrogram ablation while in AF (group 2). The procedural profiles and clinical outcomes of the 2 strategies were compared. Ninety patients were randomized to group 1 (n=46) or group 2 (n=44). There were no differences in baseline characteristics between groups. Over 365 days of follow-up after the index procedure, 16 patients (35%) in group 1 and 13 patients (30%) in group 2 remained arrhythmia-free off antiarrhythmic medications. Over long-term follow-up (median, 867 days), arrhythmia-free survival off antiarrhythmic medications was more likely in group 1 than in group 2 in Kaplan–Meier analysis (Log Rank P=0.04). Group 1 ablation was associated with significantly shorter procedural duration and fluoroscopy time (231±72 versus 273±76 min; P=0.008 and 54 [Q1–Q3: 46–67] versus 66 (Q1–Q3: 53–83] min; P=0.018, respectively). Conclusions—In patients with persistent AF, PVAI in sinus rhythm after direct current cardioversion is associated with higher success and shorter procedural and fluoroscopy times compared with PVAI in AF with additional complex-fractionated atrial electrogram ablation. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifier: NCT02429648.
Regulation of Adaptive NK Cells and CD8 T Cells by HLA-C Correlates with Allogeneic Hematopoietic Cell Transplantation and with Cytomegalovirus Reactivation

Mass cytometry was used to investigate the effect of CMV reactivation on lymphocyte reconstitution in hematopoietic cell transplant patients. For eight transplant recipients (four CMV negative and four CMV positive), we studied PBMCs obtained 6 mo after unrelated donor hematopoietic cell transplantation (HCT). Forty cell-surface markers, distinguishing all major leukocyte populations in PBMC, were analyzed with mass cytometry. This group included 34 NK cell markers. Compared with healthy controls, transplant recipients had higher HLA-C expression on CD56−CD16+ NK cells, B cells, CD33bright myeloid cells, and CD4CD8 T cells. The increase in HLA-C expression was greater for CMV-positive HCT recipients than for CMV negative recipients. Present in CMV-positive HCT recipients, but not in CMV-negative HCT recipients or controls, is a population of killer cell Ig-like receptor (KIR)-expressing CD8 T cells not previously described. These CD8 T cells coexpress CD56, CD57, and NKG2C. The HCT recipients also have a population of CD57+NKG2A+ NK cells that preferentially express KIR2DL1. An inverse correlation was observed between the frequencies of CD57+NKG2C+ NK cells and CD57+NKG2A+ NK cells. Although CD57+NKG2A+ NK cells are less abundant in CMV-positive recipients, their phenotype is of a more activated cell than the CD57+NKG2A+ NK cells of controls and CMV-negative HCT recipients. These data demonstrate that HCT and CMV reactivation are associated with an increased expression of HLA-C. This could influence NK cell education during lymphocyte reconstitution. The increased inhibitory KIR expression by proliferating CMV-specific CD8 T cells suggests regulatory interactions between HLA-C and KIR might promote Graft-versus-Leukemia effects following transplantation.
A Revised Activities of Daily Living/Instrumental Activities of Daily Living Instrument Increases Interpretive Power: Theoretical Application for Functional Tasks Exercise

Background: As the number of adults in older age groups expands, difficulty performing usual activities of daily life is a rising health concern. A common exercise regimen employed to attenuate functional decline and disability has been resistance strength training. However, recent evidence suggests that functional tasks exercise may be more effective in preventing disability. Objective: Activities of Daily Living (ADL) measures are one of the most widely used tools in gerontology, and yet the full sensitivity of these instruments is often not realized. The purpose of this study is to enhance the interpretive power of ADL by formally confirming a hierarchy of decline, assessing discriminatory power, and examining option characteristic curves. Theoretically, a revised ADL instrument can improve the efficacy of functional tasks training programs. Methods: This was a cross-sectional study that employed Item Response Theory (IRT) to interpret ADL outcomes. Participants consisted of community-dwelling older adults (n = 548, aged 79) living in Scotland. Results: A Mokken scale with ρ = 0.77 was obtained, indicating good reliability, and satisfying the IRT assumption that a single unidimensional scale is present. The set H coefficient of 0.48 indicated that the scale may be ordered by decreasing difficulty, with the ‘Cut your own toe-nails? ’ item being the most difficult and ‘Tie a good knot in a piece of string? ’ being the least difficult. Discriminatory and option characteristic parameters revealed ‘Get on a bus? ’ to be the task most closely related to the latent construct and that item options can be used to ascertain critical thresholds for prevention type strategies. Conclusions: Examining parameters relating to difficulty, discriminatory power, and option characteristics facilitated the identification of ADL/Instrumental ADL items that may serve to enhance functional task training in community-dwelling older adults. These analyses demonstrated that functional tasks have differing levels of discriminatory power, and that a task’s discriminatory power is likely to change with varying levels of disability. This observation reinforces the notion that exercises based on functional tasks may differ significantly in their therapeutic effect. Lastly, this study was able to highlight statistically meaningful cut-points relating to when older adults should begin ‘prehabilitation’ interventions.
Diel rhythms and sex differences in the locomotor activity of hawkmoths

ABSTRACT Circadian patterns of activity are considered ubiquitous and adaptive, and are often invoked as a mechanism for temporal niche partitioning. Yet, comparisons of rhythmic behavior in related animal species are uncommon. This is particularly true of Lepidoptera (butterflies and moths), in which studies of whole-animal patterns of behavior are far outweighed by examinations of tissue-specific molecular clocks. Here, we used a comparative approach to examine the circadian patterns of flight behavior in Manduca sexta and Hyles lineata [two distantly related species of hawkmoth (Sphingidae)]. By filming isolated, individual animals, we were able to examine rhythmic locomotor (flight) activity at the species level, as well as at the level of the individual sexes, and in the absence of interference from social interaction. Our results confirmed classic descriptions of strictly nocturnal behavior in M. sexta and demonstrated a dramatically different activity pattern in H. lineata. Furthermore, we showed distinct species and sex-specific differences in the maintenance of the endogenous rhythm under conditions of constant darkness. In both species, female activity peaked in advance of males whereas male activity coincided with periods of female sexual receptivity. This suggests a role for circadian patterns of locomotor activity in synchronizing periods of sexual receptivity between the sexes. Summary: Analysis of circadian rhythmicity in the locomotor activity of two hawkmoth species (Manduca sexta and Hyles lineata) reveals consistent sex differences in the timing of activity.
POU5F1 Isoforms Show Different Expression Patterns in Human Embryonic Stem Cells and Preimplantation Embryos

The contribution of the POU domain, class 5, transcription factor‐1 (POU5F1) in maintaining totipotency in human embryonic stem cells (hESCs) has been repeatedly proven. In humans, two isoforms are encoded: POU5F1_iA and POU5F1_iB. So far, no discrimination has been made between the isoforms in POU5F1 studies, and it is unknown which isoform contributes to the undifferentiated phenotype. Using immunocytochemistry, expression of POU5F1_iA and POU5F1_iB was examined in hESCs and all stages of human preimplantation development to look for differences in expression, biological activity, and relation to totipotency. POU5F1_iA and POU5F1_iB displayed different temporal and spatial expression patterns. During human preimplantation development, a significant POU5F1_iA expression was seen in all nuclei of compacted embryos and blastocysts and a clear POU5F1_iB expression was detected from the four‐cell stage onwards in the cytoplasm of all cells. The cytoplasmic localization might imply no or other biological functions beyond transcription activation for POU5F1_iB. The stemness properties of POU5F1 can be assigned to POU5F1_iA because hESCs expressed POU5F1_iA but not POU5F1_iB. However, POU5F1_iA is not the appropriate marker to identify totipotent cells, because POU5F1_iA was also expressed in the nontotipotent trophectoderm and was not expressed in zygotes and early cleavage stage embryos, which are assumed to be totipotent. The expression pattern of POU5F1_iA may suggest that POU5F1_iA alone cannot sustain totipotency and that coexpression with other stemness factors might be the key to totipotency.
Dewatering of septic tank sludge in alternative sludge drying bed

In dewatering of septic tank sludge, the sludge drying bed is one of the main techniques used, but it demands a great deal of area and time for the removal of sludge cake. Modification of this system using permeable pavements and polymer can minimize such problems, facilitating the management of sludge when decentralized sanitation is used. Therefore, the objective of this study was to compare the dewatering of septic tank sludge using conventional sludge drying bed (CSDB) and a sludge drying bed with permeable pavement (SDBPP). At the same time of dewatering, the volume drained by the SDBPP was 37.4 ± 4.6% higher than that obtained in the CSDB. Therefore, a lower drying bed could be used. It was found that the use of synthetic polymer allowed dewatering to occur in less time, but did not interfere in the solids content of the sludge cake. The reuse of the pavement was proven possible, but required large volumes of water and mechanical equipment.
Comparative molecular field analysis (CoMFA) model using a large diverse set of natural, synthetic and environmental chemicals for binding to the androgen receptor

A large number of natural, synthetic and environmental chemicals are capable of disrupting the endocrine systems of experimental animals, wildlife and humans. These so-called endocrine disrupting chemicals (EDCs), some mimic the functions of the endogenous androgens, have become a concern to the public health. Androgens play an important role in many physiological processes, including the development and maintenance of male sexual characteristics. A common mechanism for androgen to produce both normal and adverse effects is binding to the androgen receptor (AR). In this study, we used Comparative Molecular Field Analysis (CoMFA), a three-dimensional quantitative structure–activity relationship (3D-QSAR) technique, to examine AR-ligand binding affinities. A CoMFA model with and was developed using a large training data set containing 146 structurally diverse natural, synthetic, and environmental chemicals with a 106-fold range of relative binding affinity (RBA). By comparing the binding characteristics derived from the CoMFA contour map with these observed in a human AR crystal structure, we found that the steric and electrostatic properties encoded in this training data set are necessary and sufficient to describe the RBA of AR ligands. Finally, the CoMFA model was challenged with an external test data set; the predicted results were close to the actual values with average difference of 0.637 logRBA. This study demonstrates the utility of this CoMFA model for real-world use in predicting the AR binding affinities of structurally diverse chemicals over a wide RBA range.
Liver fatty acid‐binding protein is required for high rates of hepatic fatty acid oxidation but not for the action of PPAR‐α in fasting mice

Liver fatty acid binding protein (L‐FABP) has been proposed to limit the availability of long‐chain fatty acids (LCFA) for oxidation and for peroxisome proliferator‐activated receptor α (PPAR‐α), a fatty acid binding transcription factor that determines the capacity of hepatic fatty acid oxidation. Here, we used L‐FABP null mice to test this hypothesis. Under fasting conditions, this mutation reduced β‐hydroxybutyrate (BHB) plasma levels as well as BHB release and palmitic acid oxidation by isolated hepatocytes. However, the capacity for ketogenesis was not reduced: BHB plasma levels were restored by octanoate injection; BHB production and palmitic acid oxidation were normal in liver homogenates; and hepatic expression of key PPAR‐α target (MCAD, mitochondrial HMG CoA synthase, ACO, CYP4A3) and other (CPT1, LCAD) genes of mitochondrial and extramitochondrial LCFA oxidation and ketogenesis remained at wild‐type levels. During standard diet, mitochondrial HMG CoA synthase mRNA was selectively reduced in L‐FABP null liver. These results suggest that under fasting conditions, hepatic L‐FABP contributes to hepatic LCFA oxidation and ketogenesis by a nontranscriptional mechanism, whereas L‐FABP can activate ketogenic gene expression in fed mice. Thus, the mechanisms whereby L‐FABP affects fatty acid oxidation may vary with physiological condition.
A longitudinal examination of social capital as a predictor of depression

ABSTRACT Depression is the world’s most common mental health disorder and its prevalence is higher among women and the poor. This article seeks to examine the effect that social capital has on mental health, in a longitudinal study. We used data from the Fragile Families and Child Wellbeing Study, which has followed a cohort of families born in large US cities to mostly minority, unmarried parents for over 15 years. Two measures of social capital are constructed, an index of social support and trust, and a measure of social participation. Data from four waves (totalling 8 years) of the study are analyzed in a panel logit model. After controlling for socioeconomic and demographic factors, the measure of social support and trust is found to be a significant predictor of depression, and remains so even after controlling for the effect of social participation. Our measure of social participation, based on attendance at religious services, does not appear to be a significant predictor of depression. Intervention and policy initiatives that increase social capital, particularly social support and trust, may be viable for improving depression among low-income urban, minority women.
Biphasic effects of leukemia inhibitory factor on osteoblastic differentiation *

Leukemia inhibitory factor (LIF) is a cytokine produced by multiple cell types including osteoblasts and which is active on bone metabolism. We have previously shown that in a bone nodule forming in vitro model of osteogenesis, the fetal rat calvaria (RC) cell model, LIF inhibits osteoblast differentiation, acting on late osteoprogenitors and/or early osteoblasts. These results are in contrast to in vivo experiments, in which LIF has been found to increase bone formation. To resolve this discrepancy, we have tested the effect of LIF on rat bone marrow (RBM) stromal cell cultures, an in vitro model encompassing earlier osteoprogenitor stages. LIF inhibited cell growth in early, proliferating RBM cultures, but increased the culture saturation density. The effect of LIF on bone nodule formation in this model was cell density dependent and biphasic. Continuous treatment with LIF reduced the number of bone nodules present in confluent, more mature cultures, and the inhibitory effect was strongest when cells were plated at higher cell density than lower. In contrast, during the early stages of RBM culture, nodule numbers were higher in LIF‐treated dishes than in controls, and this effect was greater in lower density cultures. Acute LIF treatment restricted to early time points increased the final number of bone nodules formed in mature RBM cell cultures, but not in RC cell cultures. Our results indicate that LIF exerts complex, stage‐specific effects on osteoprogenitor recruitment, differentiation, and bone formation, and that the effects are cell nonautonomous, in the rat bone marrow stromal cell model. J. Cell. Biochem. Suppl. 36: 63–70, 2001. © 2001 Wiley‐Liss, Inc.
Data Protection and the Role of Fairness

The purpose of this article is to examine the principle of fairness as it appears in EU data protection law. Despite the fact that this principle is often referred to as a key tenet of the data protection framework, a precise understanding of its role remains elusive. As such, this article aims to provide the first steps towards a more thorough understanding of the fairness principle. This is significant as it is argued that fairness is delineated from the other data protection principles and thus this article aims to clarify its overarching role and importance in the General Data Protection Regulation (GDPR). The article divides the fairness principle into procedural fairness and fair balancing elements which are evident in the fairness checks and balances in the GDPR. Building on this analysis the article identifies gaps, shortcomings and areas for future research thus calling for further analysis on the precise contours of the fairness principle.
Unexpected patterns of mitochondrial DNA variation among Native Americans from the southeastern United States.

Mitochondrial DNA (mtDNA) haplogroups were determined by restriction fragment length polymorphism-typing for 66 individuals from four southeastern North American populations, and the HVS I portion of the mtDNA control region was sequenced in 48 of these individuals. Although populations from the same geographic region usually exhibit similar haplogroup frequency distributions (Lorenz and Smith [1996] Am. J. Phys. Anthropol. 101:307-323; Malhi et al. [2001] Hum. Biol. 73:17-55), those from the Southeast instead exhibit haplogroup frequency distributions that differ significantly from one another. Such divergent haplogroup frequency distributions are unexpected for the Muskogean-speaking southeastern populations, which share many sociocultural traits, speak closely related languages, and have experienced extensive admixture both with each other and with other eastern North American populations. Independent origins, genetic isolation from other Native American populations due to matrilocality, differential admixture, or a genetic bottleneck could be responsible for this heterogeneous distribution of haplogroup frequencies. Within a given haplogroup, however, the HVS I sequences from the four Muskogean-speaking populations appear relatively similar to one another, providing evidence for close relationships among them and for reduced diversity within haplogroups in the Southeast. Given additional archaeological, linguistic, and ethnographic evidence, these results suggest that a genetic bottleneck associated with the historical population decline is the most plausible explanation for such patterns of mtDNA variation.
High-Throughput Screen for Inhibitors of Androgen Receptor-RUNX2 Transcriptional Regulation in Prostate Cancer

Runt-related transcription factor 2 (RUNX2) plays a critical role in prostate cancer progression. RUNX2 interacts with the androgen receptor (AR) and modulates its transcriptional activity in a locus-specific manner. RUNX2 and AR synergistically stimulate a subset of genes, including the pro-oncogene snail family zinc finger 2 (SNAI2). AR-RUNX2 signaling cooperatively induces invasiveness of prostate cancer cells via SNAI2; and coexpression of AR, RUNX2, and SNAI2 in prostate cancer biopsy samples predicts disease recurrence. Competitive inhibition of AR alone could not disrupt the synergistic activation of SNAI2. We therefore established a phenotypic cell-based screening assay for compounds that could inhibit AR-RUNX2 synergistic activity either directly or indirectly. This assay was used to screen 880 compounds as a proof of concept, resulting in identification of several compounds that disrupted the synergistic stimulation of genes. Further investigation suggested the involvement of epidermal growth factor receptor (EGFR) signaling in AR/RUNX2 synergistic activity. Our assay is amenable to high-throughput screening and can be used to identify inhibitors of the AR-RUNX2 interaction in prostate cancer cells.