Miracle-dz/UniFAR-FTUs huggingface dataset:
Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes.

OBJECTIVE The purpose of this study was to determine whether abnormal placentation (defined as the failure of physiologic transformation of spiral arteries) is present in patients with preterm labor and intact membranes who delivered a preterm neonate. STUDY DESIGN A cross-sectional study was conducted to examine the histopathologic findings in the placental bed and placenta of patients with preterm labor and intact membranes (n=27), preeclampsia (n=43), and healthy pregnant women at term (n=103). Immunohistochemistry studies with cytokeratin 7 and periodic acid-Schiff were used to detect trophoblast and fibrinoid, respectively, and diagnose the failure of physiologic transformation of the spiral arteries. RESULTS The mean percentage of spiral arteries with failure of physiologic transformation in the myometrium was significantly higher in patients with preterm labor and preeclampsia than in normal pregnant women at term (P=.0004 and P<.0001, respectively). Similar findings were observed in the decidual segment of spiral arteries within the placental bed (P=.001 and P<.0001). In contrast, the mean percentage of the spiral arteries with failure of physiologic transformation in the decidua of the basal plate was not significantly different between patients with preterm labor and normal pregnant women (P=.17). CONCLUSION Failure of physiologic transformation of the spiral arteries in the myometrial and decidual segments of the placental bed is frequent in patients with preterm labor and intact membranes.
Limbic Corticostriatal Systems and Delayed Reinforcement

Abstract: Impulsive choice, one aspect of impulsivity, is characterized by an abnormally high preference for small, immediate rewards over larger delayed rewards, and can be a feature of adolescence, but also attention‐deficit/hyperactivity disorder (ADHD), addiction, and other neuropsychiatric disorders. Both the serotonin and dopamine neuromodulator systems are implicated in impulsivity; manipulations of these systems affect animal models of impulsive choice, though these effects may depend on the receptor subtype and whether or not the reward is signaled. These systems project to limbic cortical and striatal structures shown to be abnormal in animal models of ADHD. Damage to the nucleus accumbens core (AcbC) causes rats to exhibit impulsive choice. These rats are also hyperactive, but are unimpaired in tests of visuospatial attention; they may therefore represent an animal model of the hyperactive‐impulsive subtype of ADHD. Lesions to the anterior cingulate or medial prefrontal cortex, two afferents to the AcbC, do not induce impulsive choice, but lesions of the basolateral amygdala do, while lesions to the orbitofrontal cortex have had opposite effects in different tasks measuring impulsive choice. In theory, impulsive choice may emerge as a result of abnormal processing of the magnitude of rewards, or as a result of a deficit in the effects of delayed reinforcement. Recent evidence suggests that AcbC‐lesioned rats perceive reward magnitude normally, but exhibit a selective deficit in learning instrumental responses using delayed reinforcement, suggesting that the AcbC is a reinforcement learning system that mediates the effects of delayed rewards.
No evidence for association between the −112G/A polymorphism of UGRP1 and childhood atopic asthma

Background Susceptibility to asthma is known to involve genetic factors. Genome‐wide screens have indicated that the chromosome 5q31–q34 region is linked to and/or associated with asthma. A new gene, named UGRP1 and reported by Niimi et al., encodes uteroglobin‐related protein and is expressed in the lung and trachea. Niimi et al. showed the −112G/A polymorphism of the UGRP1 gene to be associated with asthma in a case–control study.
δ-Opioid Receptor Expression in the Ventral Tegmental Area Protects Against Elevated Alcohol Consumption

Alcoholism is a complex and debilitating syndrome affecting ∼140 million people worldwide. However, not everyone who consumes ethanol develops abuse, raising the possibility that some individuals have a protective mechanism that inhibits elevated alcohol consumption. We tested the hypothesis that the δ-opioid receptor (DOR) plays such a protective role. Here we show that DOR activity in the ventral tegmental area (VTA) robustly decreases ethanol consumption in rats and that these effects depend on baseline ethanol consumption. Intra-VTA microinjection of the DOR agonist DPDPE decreases drinking, particularly in low-drinking animals. Furthermore, VTA microinjection of the DOR selective antagonist TIPP-Ψ increases drinking in low, but not high, drinkers and this increase is blocked by comicroinjection of the GABAA antagonist bicuculline. Using electrophysiological techniques we found that in VTA brain slices from drinking rats DPDPE presynaptically inhibits GABAA receptor mediated IPSCs in low drinkers, but not in high drinkers or naive animals, most likely through activation of DORs on GABA terminals. This DOR-mediated inhibition of IPSCs also correlates inversely with behavioral correlates of anxiety measured in the elevated plus maze. In contrast, presynaptic inhibition of VTA GABAA IPSCs by the μ- opioid receptor agonist DAMGO is significantly reduced in both high- and low-drinking rats (<30%) compared with age-matched nondrinking controls (>70%). Together, our findings demonstrate the protective nature of VTA DORs and identify an important new target for therapeutic intervention for alcoholism.
Effect of apolipoprotein A-V on plasma triglyceride, lipoprotein size, and composition in genetically engineered mice Published, JLR Papers in Press, December 3, 2007.

Transgenic (Tg) mice that overexpress the human apolipoprotein A-V gene (APOA5) yet lack an endogenous mouse apoa5 gene (APOA5 Tg mice) were generated. Subsequently, the effect of human apoA-V expression on plasma triglyceride (TG) concentration and lipoprotein and apolipoprotein distribution was determined and compared with that in mice deficient in apoA-V (apoa5−/− mice). NMR analysis of plasma lipoproteins revealed that APOA5 Tg mice had a very low VLDL concentration (26.4 ± 7.7 nmol/dl), whereas VLDL in apoa5−/− mice was 18- fold higher (467 ± 152 nmol/dl). SDS-PAGE analysis of the d < 1.063 g/ml plasma fraction revealed that the apoB-100/apoB-48 ratio was 14-fold higher in APOA5 Tg versus apoa5−/− mice and that the apoE/total apoB ratio was 7-fold greater in APOA5 Tg versus apoa5−/− mice. It is anticipated that a reduction in apoB-100/apoB-48 ratio as well as that for apoE/apoB would impair the uptake of VLDL and remnants in apoa5−/− mice, thereby contributing to increased plasma TG levels. The concentration of apoA-V in APOA5 Tg mice was 12.5 ± 2.9 μg/ml, which is ∼50- to 100-fold higher than that reported for normolipidemic humans. ApoA-V was predominantly associated with HDL but was rapidly and efficiently redistributed to apoA- V-deficient VLDL upon incubation. Consistent with findings reported for human subjects, apoA-V concentration was positively correlated with TG levels in normolipidemic APOA5 Tg mice. It is conceivable that, in a situation in which apoA-V is chronically overexpressed, complex interactions among factors regulating TG homeostasis may result in a positive correlation of apoA-V with TG concentrations.
Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells by blocking the PDGF receptor

Hepatic fibrosis is an outcome of chronic liver diseases. The activation and proliferation of hepatic stellate cells (HSCs) is a key event in liver injury. The fruiting body of Ganoderma lucidum has long been a popular oriental medicine for treating liver diseases. The aim of this present study was to investigate the antiproliferative effects of the triterpenoid‐rich extract (GLT) of G. lucidum in a cell line of rat HSCs (HSC‐T6) stimulated with platelet‐derived growth factor (PDGF)‐BB. DNA synthesis was investigated by bromodeoxyuridine (BrdU) incorporation. Flow cytometry using propidium iodide (PI) labeling was carried out to analyse the cell cycle distribution and apoptosis. α‐Smooth muscle actin (α‐SMA) was used to evaluate extracellular matrix deposition, and western blotting was performed to measure cyclins D1 and D2, and phosphorylation of the PDGFβ‐receptor (PDGFβR), Akt and JNK. The results indicated that the GLT attenuated BrdU incorporation in a concentration‐dependent manner with an IC50 of 8.52 ± 0.33 µg/mL. The inhibitory effect of the GLT was associated with downregulation of cyclins D1 and D2, and PDGFβR and Akt phosphorylation, upregulation of JNK phosphorylation, and a reduction in α‐SMA expression. These results indicated that G. lucidum inhibits PDGF‐BB‐activated HSC proliferation possibly through blocking PDGFβR phosphorylation, thereby indicating its efficacy for preventing and treating hepatic fibrosis. Copyright © 2008 John Wiley & Sons, Ltd.
3D motion flow estimation using local all-pass filters

Fast and accurate motion estimation is an important tool in biomedical imaging applications such as motion compensation and image registration. In this paper, we present a novel algorithm to estimate motion in volumetric images based on the recently developed Local All-Pass (LAP) optical flow framework. The framework is built upon the idea that any motion can be regarded as a local rigid displacement and is hence equivalent to all-pass filtering. Accordingly, our algorithm aims to relate two images, on a local level, using a 3D all-pass filter and then extract the local motion flow from the filter. As this process is based on filtering, it can be efficiently repeated over the whole image volume allowing fast estimation of a dense 3D motion. We demonstrate the effectiveness of this algorithm on both synthetic motion flows and in-vivo MRI data involving respiratory motion. In particular, the algorithm obtains greater accuracy for significantly reduced computation time when compared to competing approaches.
Retinal Capillary Density and Foveal Avascular Zone Area Are Age-Dependent: Quantitative Analysis Using Optical Coherence Tomography Angiography.

Purpose The purpose of this study was to quantify retinal capillary density and the foveal avascular zone (FAZ) area in normal subjects according to age, using optical coherence tomography angiography (OCTA). Methods All eyes in this cross-sectional study underwent OCTA using RTVue XR Avanti with AngioVue. OCTA scans were analyzed and processed, and vessel density and FAZ dimensions were calculated. Results A total of 113 normal eyes from 70 subjects were included (30 males, 40 females; mean 48 ± 20 years of age). The mean vessel density and FAZ dimensions were significantly smaller in the superficial retinal capillary plexus (SCP) than in the deep retinal capillary plexus (DCP), using quantitative OCTA analysis (all P< 0.0001). With 3 × 3-mm scans, the mean vessel density was 13.431 ± 1.758 mm-1 in the SCP, 18.812 ± 1.796 mm-1 in the DCP, and 5.913 ± 1.308 mm-1 and 10.447 ± 1.262 mm-1 with 6 × 6-mm scans in the SCP and DCP, respectively. Mean FAZ areas were 0.289 ± 0.108 mm2 at the SCP and 0.614 ± 0.200 mm2 at the DCP. Age was a predictor of SCP and DCP vessel density and FAZ area in the SCP. Vessel density decreased 0.0393 mm-1 (0.26%) per year in the SCP and 0.0574 mm-1 (0.27%) per year in the DCP. FAZ areas increased 0.0014 mm2 (0.63%) and 0.0011 mm2 (0.20%) per year in the SCP and DCP, respectively. Conclusions SCP and DCP vessel density decreased with increasing age, while FAZ area increased with age. Normal age-matched measurements provide important standardized values that may facilitate management of retinal vascular disorders.
Effects of moderating factors including serotonin transporter polymorphisms on smoking behavior: a systematic review and meta-analysis update.

INTRODUCTION The aim of this review was to report an update of a previous meta-analysis (by another group) of a possible relationship between serotonin transporter (5-HTTLPR) genotype and smoking behavior, and extend previous work by factoring in some demographic parameters (age, gender, and ethnicity) in a multiple regression model to examine the relationship between these demographic factors and the effect of 5-HTTLPR polymorphism on smoking behavior. METHODS Effect sizes were calculated for each study selected for meta-analysis and were pooled using the random-effects model, which assumes within-study sampling and between-study variance and provides wider confidence intervals. Effect sizes calculated in each study were used to evaluate the correlations with participant data for age, gender, and ethnicity (moderating variable) by multiple regression analysis. RESULTS Meta-analysis indicated a relationship between smoking rate and the 5-HTTLPR genotype, but not smoking initiation and persistence, which was consistent with that of the previous review. Publication bias was not indicated for smoking initiation or persistence. Multiple regression analysis revealed that mean participant age significantly affected effect sizes for smoking initiation and persistence of each study. The proportion of Caucasians may have been partially influenced by the difference in effect sizes for smoking persistence among the studies. CONCLUSION A significant relationship stratified by ancestry was observed between the 5-HTTLPR genotype and smoking rate, but not between the 5-HTTLPR genotype and smoking initiation and persistence. Regression analysis detected effects of age and/or ethnicity as moderating factors on smoking initiation and persistence.
Therapeutics , Targets , and Chemical Biology 4-Hydroxytamoxifen Induces Autophagic Death through KRas Degradation

Tamoxifen is widely used to treat estrogen receptor–positive breast cancer. Recent findings that tamoxifen and its derivative 4-hydroxytamoxifen (OHT) can exert estrogen receptor–independent cytotoxic effects have prompted the initiation of clinical trials to evaluate its use in estrogen receptor–negative malignancies. For example, tamoxifen and OHT exert cytotoxic effects in malignant peripheral nerve sheath tumors (MPNST) where estrogen is not involved. In this study, we gained insights into the estrogen receptor–independent cytotoxic effects of OHT by studying how it kills MPNST cells. Although caspases were activated following OHT treatment, caspase inhibition provided no protection from OHT-induced death. Rather, OHT-induced death in MPNST cells was associated with autophagic induction and attenuated by genetic inhibition of autophagic vacuole formation. Mechanistic investigations revealed that OHT stimulated autophagic degradation of K-Ras, which is critical for survival of MPNST cells. Similarly, we found that OHT induced K-Ras degradation in breast, colon, glioma, and pancreatic cancer cells. Our findings describe a novel mechanism of autophagic death triggered by OHT in tumor cells that may be more broadly useful clinically in cancer treatment. Cancer Res; 73(14); 4395–405. 2013 AACR.
Multiple Purkinje Cell Recording in Rodent Cerebellar Cortex

The spatial and temporal organization of climbing fibre activation of Purkinje cells, the so‐called complex spikes, were studied in the rat cerebellar Crus II folium utilizing a multiple microeletrode recording technique. As many as 32 Purkinje cells could be simultaneously recorded by using a custom‐built electronic amplifier system and a special data storage device. Analysis of the auto‐correlation activity of complex spikes in any given group of Purkinje cells indicated that activation occurs with a particular rhythmicity having a base firing of 10 Hz. Cross‐correlation of spontaneous complex spikes demonstrated, in addition to a particular rhythmicity, an extraordinarily high degree of synchronicity within a particular spatial distribution of Purkinje cells. Thus, Purkinje cells organized in rostra‐caudal rows tend to fire within 1 ms of each other for distances as far as 800 μm (the width of a folium) from the ‘master’ neuron. By contrast, Purkinje cells located medial or lateral to the master neuron showed almost no cross‐correlation. Administration of harmaline to the animal increased the degree of auto‐ and cross‐correlation but did not change the spatial order of the distribution of the cross‐correlation. The results indicate that the olivo‐cerebellar system is organized in such a way that climbing fibre afferents may be activated in a close‐to‐synchronous and rhythmic fashion. The spatial distribution of these afferents over the cortex is such as to activate rostro‐caudal bands of Purkinje cells which tend to fire in a close‐to‐synchronous manner.
Does Litigation Increase or Decrease Health Care Quality?: A National Study of Negligence Claims Against Nursing Homes

Background:The tort system is supposed to help improve the quality and safety of health care, but whether it actually does so is controversial. Most previous studies modeling the effect of negligence litigation on quality of care are ecologic. Objective:To assess whether the experience of being sued and incurring litigation costs affects the quality of care subsequently delivered in nursing homes. Research Design, Subjects, Measures:We linked information on 6471 negligence claims brought against 1514 nursing homes between 1998 and 2010 to indicators of nursing home quality drawn from 2 US national datasets (Online Survey, Certification, and Reporting system; Minimum Data Set Quality Measure/Indicator Reports). At the facility level, we tested for associations between 9 quality measures and 3 variables indicating the nursing homes’ litigation experience in the preceding 12–18 months (total indemnity payments; total indemnity payments plus administrative costs; ≥1 paid claims vs. none). The analyses adjusted for quality at baseline, case-mix, ownership, occupancy, year, and facility and state random effects. Results:Nearly all combinations of the 3 litigation exposure measures and 9 quality measures—27 models in all—showed an inverse relationship between litigation costs and quality. However, only a few of these associations were statistically significant, and the effect sizes were very small. For example, a doubling of indemnity payments was associated with a 1.1% increase in the number of deficiencies and a 2.2% increase in pressure ulcer rates. Conclusions:Tort litigation does not increase the quality performance of nursing homes, and may decrease it slightly.
Automatic Fastener Classification and Defect Detection in Vision-Based Railway Inspection Systems

The detection of fastener defects is an important task in railway inspection systems, and it is frequently performed to ensure the safety of train traffic. Traditional inspection is usually operated by trained workers who walk along railway lines to search for potential risks. However, the manual inspection is very slow, costly, and dangerous. This paper proposes an automatic visual inspection system for detecting partially worn and completely missing fasteners using probabilistic topic model. Specifically, our method is able to simultaneously model diverse types of fasteners with different orientations and illumination conditions using unlabeled data. To assess the damages, the test fasteners are compared with the trained models and automatically ranked into three levels based on the likelihood probability. The experimental results demonstrate the effectiveness of this method.
Epidemiology of the Association Between Somatoform Disorders and Anxiety and Depressive Disorders: An Update

Objective: To review the available epidemiological evidence on associations between somatoform disorders with anxiety and depressive disorders. Results: Clinical and population-based studies have found that the co-occurrence of some types of somatoform disorders (e.g., somatization disorder, somatic-symptom-index (SSI)4,6, and pain disorder) and anxiety and depressive disorders is common. These findings may suggest either a causal relationship between these disorders or that they share some common etiological factors. For other forms of somatoform disorders, empirical evidence about co-occurrence is even thinner or not available at all, especially from non-western settings. Conclusion: Some implications of how these findings, or the absence of them, can help us understand better the etiology of somatoform disorders and improve the classification of mental disorders as a whole are discussed. DSM = Diagnostic and Statistical Manual of Mental Disorders; DIS = Diagnostic Interview Schedule; ECA = Epidemiological Catchment Area Program; FGD = functional gastrointestinal disorders; GAD = general anxiety disorder; OR = odds ratio; PTSD = posttraumatic stress disorder; SSI = Somatic Symptom Index.
Rapid Induction of Allergic Encephalomyelitis in Rats without the Use of Mycobacteria

Rats, in contrast to certain other species of animals reported, have a striking capacity to develop allergic encephalomyelitis within 2 to 3 weeks following one injection of spinal cord antigen combined with Freund's incomplete adjuvant—that is, adjuvant prepared without addition of killed mycobacteria.
TNFR-Associated Factor 2 Deficiency in B Lymphocytes Predisposes to Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in Mice

We have previously shown that transgenic (tg) mice expressing in B lymphocytes both BCL-2 and a TNFR-associated factor 2 (TRAF2) mutant lacking the really interesting new gene and zinc finger domains (TRAF2DN) develop small lymphocytic lymphoma and chronic lymphocytic leukemia with high incidence (Zapata et al. 2004. Proc. Nat. Acad. Sci. USA 101: 16600–16605). Further analysis of the expression of TRAF2 and TRAF2DN in purified B cells demonstrated that expression of both endogenous TRAF2 and tg TRAF2DN was negligible in Traf2DN-tg B cells compared with wild-type mice. This was the result of proteasome-dependent degradation, and rendered TRAF2DN B cells as bona fide TRAF2-deficient B cells. Similar to B cells with targeted Traf2 deletion, Traf2DN-tg mice show expanded marginal zone B cell population and have constitutive p100 NF-κB2 processing. Also, TRAF3, X-linked inhibitor of apoptosis, and Bcl-XL expression levels were increased, whereas cellular inhibitors of apoptosis 1 and 2 levels were drastically reduced compared with those found in wild-type B cells. Moreover, consistent with previous results, we also show that TRAF2 was required for efficient JNK and ERK activation in response to CD40 engagement. However, TRAF2 was deleterious for BCR-mediated activation of these kinases. In contrast, TRAF2 deficiency had no effect on CD40-mediated p38 MAPK activation but significantly reduced BCR-mediated p38 activation. Finally, we further confirm that TRAF2 was required for CD40-mediated proliferation, but its absence relieved B cells of the need for B cell activating factor for survival. Altogether, our results suggest that TRAF2 deficiency cooperates with BCL-2 in promoting chronic lymphocytic leukemia/small lymphocytic lymphoma in mice, possibly by specifically enforcing marginal zone B cell accumulation, increasing X-linked inhibitor of apoptosis expression, and rendering B cells independent of B cell activating factor for survival.