Miracle-dz/UniFAR-FTUs huggingface dataset:
Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial.

PURPOSE To determine the clinical significance of flow cytometric minimal residual disease (MRD) quantification in chronic lymphocytic leukemia (CLL) in addition to pretherapeutic risk factors and to compare the prognostic impact of MRD between the arms of the German CLL Study Group CLL8 trial. PATIENTS AND METHODS MRD levels were prospectively quantified in 1,775 blood and bone marrow samples from 493 patients randomly assigned to receive fludarabine and cyclophosphamide (FC) or FC plus rituximab (FCR). Patients were categorized by MRD into low- (< 10(-4)), intermediate- (≥ 10(-4) to <10(-2)), and high-level (≥ 10(-2)) groups. RESULTS Low MRD levels during and after therapy were associated with longer progression-free survival (PFS) and overall survival (OS; P < .0001). Median PFS is estimated at 68.7, 40.5, and 15.4 months for low, intermediate, and high MRD levels, respectively, when assessed 2 months after therapy. Compared with patients with low MRD, greater risks of disease progression were associated with intermediate and high MRD levels (hazard ratios, 2.49 and 14.7, respectively; both P < .0001). Median OS was 48.4 months in patients with high MRD and was not reached for lower MRD levels. MRD remained predictive for OS and PFS in multivariate analyses that included the most important pretherapeutic risk markers in CLL. PFS and OS did not differ between treatment arms within each MRD category. However, FCR induced low MRD levels more frequently than FC. CONCLUSION MRD levels independently predict OS and PFS in CLL. Therefore, MRD quantification might serve as a surrogate marker to assess treatment efficacy in randomized trials before clinical end points can be evaluated.
Assessment of dietary patterns in nutritional epidemiology: principal component analysis compared with confirmatory factor analysis.

BACKGROUND In the field of nutritional epidemiology, principal component analysis (PCA) has been used to derive patterns, but the robustness of interpretation might be an issue when the sample size is small. The authors proposed the alternative use of confirmatory factor analysis (CFA) to define such patterns. OBJECTIVE The aim was to compare dietary patterns derived through PCA and CFA used as equivalent approaches in terms of stability and relevance. DESIGN PCA and CFA were performed in 2 different studies: the Epidemiological Study on the Genetics and Environment of Asthma 2-France (EGEA2-France; n = 1236) and the Phenotype and Course of Chronic Obstructive Pulmonary Disease study-Spain (n = 274). To check for stability, PCA and CFA were also performed in 2 subsamples from the EGEA2 study (n = 618 and 309). Statistical proprieties were evaluated by 1000 bootstrapped random sets of observations for each of the 4 subsamples. For each random set of observations, the distribution of the factor loading for each pattern was obtained and represented by using box-plots. To check for relevance, partial correlations between different nutrients and the different patterns derived by either PCA or CFA were calculated. RESULTS With the use of CFA, 2 consistent dietary patterns were derived in each subsample (the Prudent and the Western patterns), whereas dietary factors were less interpretable with the use of PCA (smaller median of factor loadings and higher dispersion), especially for the smallest subsample. Higher correlations were reported among total fiber, vitamins, minerals, and total lipids with patterns derived by using CFA than with patterns derived by using PCA. CONCLUSION The current study shows that CFA may be a useful alternative to PCA in epidemiologic studies, especially when the sample size is small.
Anatomic Localization and Quantitative Analysis of Gradient Refocused Echo-Planar fMRI Susceptibility Artifacts

Functional magnetic resonance imaging (fMRI) techniques, such as echo-planar imaging, can permit rapid, sensitive, whole-brain measurements of local blood flow-induced MR signal changes seen during cognitive paradigms. Changes in blood oxygenation due to mismatch of flow and oxygen metabolism cause dynamic variations in microscopic susceptibility effects, leading to the blood oxygenation level-dependent (BOLD) signal measured by fMRI techniques. A related static macroscopic susceptibility effect is known to cause artifacts that attenuate the MR signal, leading to "blind spots" in some regions of brain adjacent to bone and air sinuses. The anatomical location, spatial extent, and magnitude of signal loss artifact are quantitated for a common whole-brain fMRI technique. Resting gradient-echo EPI studies were obtained in four healthy volunteers. Signal loss was primarily localized to inferior frontal regions (medial orbital gyri and gyrus rectus) and to inferior lateral temporal lobe (including part of fusiform gyrus) bilaterally. Increased echo time (TE) uniformly produced larger artifacts. The orientation of acquired slices and choice of phase-encoding direction influenced the location, shape, and extent of the artifacts. Regions of the brain with severe artifact may have attenuated activation signal, with potential implications for the design and interpretation of fMRI studies targeting activations in these areas.
The Long Way From Government Open Data to Mobile Health Apps: Overcoming Institutional Barriers in the US Federal Government

Background Government agencies in the United States are creating mobile health (mHealth) apps as part of recent policy changes initiated by the White House’s Digital Government Strategy. Objective The objective of the study was to understand the institutional and managerial barriers for the implementation of mHealth, as well as the resulting adoption pathways of mHealth. Methods This article is based on insights derived from qualitative interview data with 35 public managers in charge of promoting the reuse of open data through Challenge.gov, the platform created to run prizes, challenges, and the vetting and implementation of the winning and vendor-created apps. Results The process of designing apps follows three different pathways: (1) entrepreneurs start to see opportunities for mobile apps, and develop either in-house or contract out to already vetted Web design vendors; (2) a top-down policy mandates agencies to adopt at least two customer-facing mobile apps; and (3) the federal government uses a policy instrument called “Prizes and Challenges”, encouraging civic hackers to design health-related mobile apps using open government data from HealthData.gov, in combination with citizen needs. All pathways of the development process incur a set of major obstacles that have to be actively managed before agencies can promote mobile apps on their websites and app stores. Conclusions Beyond the cultural paradigm shift to design interactive apps and to open health-related data to the public, the managerial challenges include accessibility, interoperability, security, privacy, and legal concerns using interactive apps tracking citizen.
Folding mechanism of the (H3–H4)2 histone tetramer of the core nucleosome

To further understand oligomeric protein assembly, the folding and unfolding kinetics of the H3–H4 histone tetramer have been examined. The tetramer is the central protein component of the core nucleosome, which is the basic unit of DNA compaction into chromatin in the eukaryotic nucleus. This report provides the first kinetic folding studies of a protein containing the histone fold dimerization motif, a motif observed in several protein–DNA complexes. Previous equilibrium unfolding studies have demonstrated that, under physiological conditions, there is a dynamic equilibrium between the H3–H4 dimer and tetramer species. This equilibrium is shifted predominantly toward the tetramer in the presence of the organic osmolyte trimethylamine‐N‐oxide (TMAO). Stopped‐flow methods, monitoring intrinsic tyrosine fluorescence and far‐UV circular dichroism, have been used to measure folding and unfolding kinetics as a function of guanidinium hydrochloride (GdnHCl) and monomer concentrations, in 0 and 1 M TMAO. The assignment of the kinetic phases was aided by the study of an obligate H3–H4 dimer, using the H3 mutant, C110E, which destabilizes the H3–H3′ hydrophobic four‐helix bundle tetramer interface. The proposed kinetic folding mechanism of the H3–H4 system is a sequential process. Unfolded H3 and H4 monomers associate in a burst phase reaction to form a dimeric intermediate that undergoes a further, first‐order folding process to form the native dimer in the rate‐limiting step of the folding pathway. H3–H4 dimers then rapidly associate with a rate constant of ≥107 M−1sec−1 to establish a dynamic equilibrium between the fully assembled tetramer and folded H3–H4 dimers.
Increased bone resorption and osteopenia in Dlx5 heterozygous mice

Distal‐less (Dlx) homeobox transcription factors play a central role in the control of osteogenesis. In particular, Dlx5 regulates osteoblasts/osteoclasts coupling during perinatal bone formation. We analyze here the effect of Dlx5 allelic reduction in the control of bone remodeling. We first show that Dlx5 expression persists during postnatal bone development. We then compare the skeletal phenotype of 10‐ and 20‐week‐old Dlx5+/− mice to that of wild‐type (WT) littermates. Dlx5+/− male mice exhibit lower bone mineral density (BMD) at both ages while only 20‐week‐old females are affected. µCT analyses reveal a reduction in cortical thickness of femoral midshafts in Dlx5+/− mice. Histomorphometry on distal femora shows no changes in trabecular structure and confirms a reduction in Dlx5+/− cortical thickness. The cortical decrease of 10‐week‐old mice does not derive from a reduction in periosteal bone apposition, but results from increased bone resorption with a significantly higher number of endosteal osteoclasts per bone surface and a larger marrow diameter. Urinary level of deoxypyridinoline is also higher in heterozygous mice confirming an increase in bone resorption activity. Our findings might be relevant for understanding complex, multifactorial diseases such as osteoporosis in which quantitative deregulation of gene expression leads to disruption of bone homeostasis. J. Cell. Biochem. 107: 865–872, 2009. © 2009 Wiley‐Liss, Inc.
Temporal monitoring of the nor‐1 (aflD) gene of Aspergillus flavus in relation to aflatoxin B1 production during storage of peanuts under different water activity levels

Aims: A relative quantification system (RQ‐PCR) was used to monitor the correlations between the activity of the nor‐1 (=aflD) gene of Aspergillus flavus using real‐time PCR in relation to phenotypic aflatoxin B1 (AFB1) production and populations of A. flavus in stored peanuts at three water activity levels (aw, 0·95, 0·90 and 0·85) for 6 weeks.
Tauroursodeoxycholic Acid Partially Prevents Apoptosis Induced by 3‐Nitropropionic Acid

Abstract: Ursodeoxycholic acid (UDCA) has been shown to be a strongmodulator of the apoptotic threshold in both hepatic and nonhepatic cells.3‐Nitropropionic acid (3‐NP), an irreversible inhibitor of succinatedehydrogenase, appears to cause apoptotic neuronal cell death in the striatum,reminiscent of the neurochemical and anatomical changes associated withHuntington's disease (HD). This study was undertaken (a) to characterizefurther the mechanism by which 3‐NP induces apoptosis in rat neuronal RN33Bcells and (b) to determine if and how the taurine‐conjugated UDCA,tauroursodeoxycholic acid (TUDCA), inhibits apoptosis induced by 3‐NP. Ourresults indicate that coincubation of cells with TUDCA and 3‐NP was associatedwith an ∼80% reduction in apoptosis (p < 0.001), whereasneither taurine nor cyclosporin A, a potent inhibitor of the mitochondrialpermeability transition (MPT), inhibited cell death. Moreover, TUDCA, as wellas UDCA and its glycine‐conjugated form, glycoursodeoxycholic acid, preventedmitochondrial release of cytochrome c (p < 0.001), whichprobably accounts for the observed inhibition of DEVD‐specific caspaseactivity and poly(ADP‐ribose) polymerase cleavage. 3‐NP decreasedmitochondrial transmembrane potential (p < 0.001) and increasedmitochondrial‐associated Bax protein levels (p < 0.001). Coincubation with TUDCA was associated with significant inhibition of thesemitochondrial membrane alterations (p < 0.01). The results suggestthat TUDCA inhibits 3‐NP‐induced apoptosis via direct inhibition ofmitochondrial depolarization and outer membrane disruption, together withmodulation of Bax translocation from cytosol to mitochondria. In addition,cell death by 3‐NP apparently occurs through pathways that are independent ofthe MPT.
Accuracy of diffusion tensor magnetic resonance imaging tractography assessed using intraoperative subcortical stimulation mapping and magnetic source imaging.

OBJECT Resecting brain tumors involves the risk of damaging the descending motor pathway. Diffusion tensor (DT)-imaged fiber tracking is a noninvasive magnetic resonance (MR) technique that can delineate the subcortical course of the motor pathway. The goal of this study was to use intraoperative subcortical stimulation mapping of the motor tract and magnetic source imaging to validate the utility of DT-imaged fiber tracking as a tool for presurgical planning. METHODS Diffusion tensor-imaged fiber tracks of the motor tract were generated preoperatively in nine patients with gliomas. A mask of the resultant fiber tracks was overlaid on high-resolution T1- and T2-weighted anatomical MR images and used for stereotactic surgical navigation. Magnetic source imaging was performed in seven of the patients to identify functional somatosensory cortices. During resection, subcortical stimulation mapping of the motor pathway was performed within the white matter using a bipolar electrode. RESULTS A total of 16 subcortical motor stimulations were stereotactically identified in nine patients. The mean distance between the stimulation sites and the DT-imaged fiber tracks was 8.7 +/- 3.1 mm (+/- standard deviation). The measured distance between subcortical stimulation sites and DT-imaged fiber tracks combines tracking technique errors and all errors encountered with stereotactic navigation. CONCLUSIONS Fiber tracks delineated using DT imaging can be used to identify the motor tract in deep white matter and define a safety margin around the tract.
Evidence Against Altered Expression of GLUT1 or GLUT4 in Skeletal Muscle of Patients With Obesity or NIDDM

Studies of experimental diabetes in rodents induced by the β-cell toxin streptozocin have shown that the insulin-resistant glucose transport of peripheral tissues (muscle and adipose) in these animals can be ascribed in part to a pretranslational reduction of the major insulin-sensitive glucose transporter (GLUT4) in these tissues. Because a central feature of non-insulin-dependent diabetes mellitus (NIDDM) is an impaired ability of insulin to enhance glucose disposal in skeletal muscle, we examined the hypothesis that reduced expression of GLUT4 is a characteristic finding in the skeletal muscle of subjects with NIDDM. Biopsies of skeletal muscles were obtained from 17 patients with NIDDM and 10 lean and 9 obese nondiabetic subjects. Among the diabetic subjects, 7 were newly diagnosed and untreated. Compared with age-matched and body-weight-matched healthy control subjects, there was no significant alteration in the level of GLUT4 mRNA demonstrated by Northern blot and slot blot or GLUT4 protein determined by immunoblotting muscle membranes. Neither GLUT4 mRNA nor protein concentration correlated with the degree of glycemic control, fasting plasma insulin or glucose, diabetes duration, body mass index, sex, or age. GLUT1 mRNA and protein levels were also not significantly different between diabetic and matched control subjects. Thus, unlike streptozocin-induced diabetes in rodents, there is no evidence that impaired expression of the major insulin-responsive glucose transporter is responsible for insulin-resistant glucose transport in the skeletal muscle of these lean and moderately obese NIDDM patients.
Unified hybrid (Ac/Dc) active distribution networks droop-based load-sharing strategy

Dc transmission and distribution will become more common in the future as power electronics technology advances and costs are reduced. This work describes a novel hybrid droop-based unified strategy for power sharing among both ac and dc generating units within a hybrid ac/dc active power distribution network. The hybrid droop power sharing strategy is discussed, the proposed approach for controlling power inverters is presented and simulations using MATLAB/Simulink and SimPowerSystems are carried out. These show satisfactory results that confirm the effectiveness of the hybrid droop strategy. An experimental microgrid setup and preliminary results are presented.
Racial differences in perception of healthy body weight in midlife women: results from the Do Stage Transitions Result in Detectable Effects study

ObjectivePerception of healthy body weight may influence health behaviors, including physical activity level, nutritional habits, and health outcomes, and these perceptions may vary importantly by race. Midlife is a critical period for women that typically includes weight gain. We assessed the associations between perception of healthy body weight and body mass index (BMI) and whether they vary by race. MethodsIn the Do Stage Transitions Result in Detectable Effects study, BMI and perception of body weight (healthy, underweight, or overweight) were measured at baseline examination. Multinomial logistic regression models examined the associations, with race (white vs black) as moderator variable. ResultsOf 729 women enrolled, 689 women (95%; black, n = 145; white, n = 544) were included in these analyses. Even though the average BMI was higher for black women than for white women (33.1 vs 29.2 kg/m2, respectively; P < 0.0001), black women were less likely to report that they weighed too much (relative risk ratio, 0.4; 95% CI, 0.2-0.9; P = 0.022) and more likely to think that they did not weigh enough (relative risk ratio, 14.2; 95% CI, 1.8-110; P = 0.011). ConclusionsAlthough black women, in general, face a greater threat of morbidity from weight-related chronic diseases, they are more likely to be accepting of their weight at higher BMIs relative to whites. Weight loss interventions and counseling about healthy body size may influence healthy behavior and reduce the risk of chronic diseases.
Erythrocyte antioxidant defenses as a potential biomarker of liver mitochondrial status in different oxidative conditions

The need for minimally invasive biomarkers to predict the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis is a priority. Oxidative stress and mitochondrial dysfunction contribute in this physiopathological process. The aim of this study was to analyze the potential role of erythrocytes as surrogate biomarkers of hepatic mitochondrial oxidative status in an animal model under different dietary oxidative conditions. Interestingly, we found that erythrocyte antioxidant status correlated with triglyceride content (p < 0.05–p < 0.001), thiobarbituric acid reactive species levels (p < 0.001) and with liver mitochondrial antioxidant levels (p < 0.001). These data suggest that erythrocyte antioxidant defenses could be used as sensitive and minimally invasive biomarkers of mitochondrial status in diverse oxidative conditions.
Total chemical synthesis of a functional interacting protein pair: The protooncogene H-Ras and the Ras-binding domain of its effector c-Raf1

Generation of biological function by chemical methods is potentially of great importance for the understanding and targeting of physiological processes. Chemical synthesis of proteins offers the ability to alter the properties of target protein molecules in a tailor-made fashion. In the present work it is demonstrated that this methodology can be expanded to the elucidation of protein–protein interactions as exemplified by the complete chemical synthesis of the protooncogene product H-Ras as well as of the Ras-binding domain (RBD) of its effector c-Raf1. The 166-aa polypeptide chain of H-Ras was synthesized by native chemical ligation of three unprotected peptide segments. Similarly, the 81-aa RBD was prepared by ligation of two peptide segments. Both RBD and Ras displayed functional and spectroscopic properties indistinguishable from their recombinant forms as judged by CD spectroscopy and from transient kinetic measurements of the Ras–RBD interaction as well as from nucleotide replacement reactions in Ras. An unnatural amino acid bearing a nitrobenzofurazan side chain was introduced into position 91 of the RBD, providing unique fluorescence properties. The association transient of nitrobenzofurazan labeled with Ras⋅guanosine 5′-β,γ-imidotriphosphate showed a slow phase that had not been detected in earlier work by using other signals.
Serological, Hematologic, and PCR Studies of Cattle in an Area of Switzerland in Which Tick-Borne Fever (Caused by Ehrlichia phagocytophila) Is Endemic

ABSTRACT The purpose of this study was to examine the seasonal variations in seroprevalence to Ehrlichia phagocytophila in cattle pastured during the summer months in an area where tick-borne fever is endemic. The study was performed during a 1-year period from April 1996 to March 1997 and involved 34 cows, 22 pregnant heifers, and 14 calves. Blood samples, collected from all 70 cattle once a month, were used to determine serum immunoglobulin G titers by indirect immunofluorescence. In addition, blood smears were examined for Ehrlichiaorganisms, and PCR amplification was performed for the molecular detection of E. phagocytophila. Prior to the pasture period, the seroprevalence was 16%. Two weeks after the start of pasturing, it was 43%, after which it progressively increased and reached a maximum of 63% in September. The seroprevalence progressively decreased after the end of pasturing to a low of 23%. The variation in antibody titers was similar to that of seroprevalence.E. phagocytophila organisms were detected in blood smears of 7 animals and by nested PCR in 12. Only four cows, which were on the pastures of endemicity for the first time, had clinical signs of ehrlichiosis. This study demonstrated marked seasonal variations in seroprevalence and in serum titers of antibody to E. phagocytophila in cattle. The incidence of clinical signs of ehrlichiosis was increased in cattle grazing on the pastures of endemicity for the first time.
Adaptive Fuzzy-Neural-Network Design for Voltage Tracking Control of a DC–DC Boost Converter

In this study, an adaptive fuzzy-neural-network control (AFNNC) scheme is designed for the voltage tracking control of a conventional dc-dc boost converter. First, the description of the circuit framework of a conventional boost converter and system modeling is introduced. Then, a total sliding-mode control (TSMC) strategy without the reaching phase in the conventional SMC is developed for enhancing system robustness during the transient response of the voltage control. In order to alleviate the control chattering phenomena caused by the sign function in the TSMC design and relax the requirement of detailed system dynamics, an AFNNC scheme is further investigated to imitate the TSMC law for the boost converter. In the AFNNC scheme, online learning algorithms are derived in the sense of Lyapunov stability theorem and projection algorithm to ensure the stability of the controlled system without the requirement of auxiliary compensated controllers despite the existence of uncertainties. The output of the AFNNC scheme can be easily supplied to the duty cycle of the power switch in the boost converter without strict constraints on control parameters selection in conventional control strategies. In addition, the effectiveness of the proposed AFNNC scheme is verified by realistic experimentations, and its advantages are indicated in comparison with the TSMC strategy.