Miracle-dz/UniFAR-FTUs huggingface dataset:
Early versus late start of immunosuppressive therapy in idiopathic membranous nephropathy: a randomized controlled trial.

BACKGROUND Immunosuppressive therapy in idiopathic membranous nephropathy (iMN) is debated. Accurate identification of patients at high risk for end-stage renal disease (ESRD) allows early start of therapy in these patients. It is unknown if early start of therapy is more effective and/or less toxic than late start (i.e. when GFR deteriorates). METHODS We conducted a randomized open-label study in patients with iMN, a normal renal function and a high risk for ESRD (urinary beta2m >0.5 microg/min, UIgG >125 mg/day). Patients started with immunosuppressive therapy (cyclophosphamide for 12 months, and steroids) either immediately after randomization or when renal function deteriorated (DeltasCr > or =+25% and sCr >135 micromol/l or DeltasCr > or =+50%). End points were remission rates, duration of the nephrotic syndrome (NS), renal function and complications. RESULTS The study included 26 patients (24 M/2 F), age 48 +/- 12 years; sCr 96 micromol/l (range 68-126) and median proteinuria 10.0 g/10 mmol Cr. Early treatment resulted in a more rapid onset of remission (P = 0.003) and a shorter duration of the NS (P = 0.009). However, at the end of the follow-up (72 +/- 22 m), there were no differences in overall remission rate, sCr (93 versus 105 micromol/l), proteinuria, relapse rate and adverse events. CONCLUSIONS In high-risk patients with iMN, immunosuppressive treatment is effective in inducing a remission. Early treatment shortens the duration of the nephrotic phase, but does not result in better preservation of renal function. Our study indicates that treatment decisions must be based on risk and benefit assessment in the individual patient.
Socioemotional Factors in Child Sexual Abuse Investigations

Two socioemotional factors were explored in association with children's production of forensic information during sexual abuse investigations: rapport building and interviewer's support. The study tested to what extent (a) the length and questioning style in the rapport-building session and (b) the level of support interviewers provided to the children, were associated with the amount of forensic details children provided in their investigation. These associations were explored for more talkative and less talkative children as well as for children of two age groups (4-6 and 7-9 years). A total of 71 forensic interviews of alleged victims of child sexual abuse were subject to a detailed psycholinguistic analysis. Results suggest that richer information in the child's responses is associated with a short and open style rapport-building session as well as with a higher level of interviewer's support. This association is especially marked for less talkative children who might be in special need of support and for whom the rapport with the interviewer might be more meaningful.
High-performance liquid chromatography-tandem mass spectrometry as a reference for analysis of tacrolimus to assess two immunoassays in patients with liver and renal transplants.

The accuracy and imprecision of three assays used for therapeutic monitoring of tacrolimus were tested using blood-containing weighed-in amounts of the drug, an enzyme-linked immunosorbent assay (ELISA), a microparticle enzyme immunoassay (MEIA I), and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS2) assay. Accuracy was acceptable for the HPLC-MS2 assay at all concentrations tested (< 10% deviation) and for the ELISA at 1.0 and 4.0 microg/l. Accuracy was not acceptable for the ELISA at 15.0 and 50.0 microg/l or for the MEIA I at all concentrations tested. Imprecision was acceptable for the HPLC-MS2 assay at all concentrations tested (coefficient of variation < 10%), for the ELISA at 15.0 and 50.0 microg/l, and for the MEIA I at 15.0 and 50.0 microg/l. Imprecision was not acceptable for the ELISA at 1.0 and 4.0 microg/l or for the MEIA I at 1.0 and 4.0 microg/l. This assessment with weighed-in amounts of tacrolimus verified the HPLC-MS2 assay as a reference method. The performance of the two immunoassays with HPLC-MS2 was then compared in the clinical setting using blood from patients with liver (n = 30) and renal (n = 37) transplants. In the liver transplant group (127 samples), the range of tacrolimus concentrations measured by HPLC-MS2, ELISA, and MEIA I was 1.9 to 31.8, 2.1 to 35.0, and less than 0.1 to 36.5 mg/l, respectively. In the renal transplant group (129 samples), the ranges were 1.7 to 26.1, 1.9 to 24.4, and 0.9 to 28.5 microg/l, respectively. Compared with the HPLC-MS2, the ELISA had minimal bias (0.1 to 0.2 microg/l) but unacceptable variability in values (SD > 13%). The MEIA I had unacceptable bias (1.7-1.8 microg/l) and variability (SD > 23%). These data indicated that neither the ELISA nor MEIA I is interchangeable with HPLC-MS2. Moreover, in view of the current trend to reduce the therapeutic dose of tacrolimus, quantitative results using the MEIA I would not be obtainable during therapeutic drug monitoring in some patients in whom effective therapeutic concentrations can be less than 5.0 microg/l.
The effect of leads on cognitive load and learning in a conceptually rich hypertext environment

iv Introduction . 1 Cognitive Processing of Hypertext . 2 Cognitive Load and Hypertext . 4 Working Memory Limitations . 6 Effects of Split Attention . 7 Research Design . 10 Literature Review . 12 Theoretical Foundations . 12 Cognitive Flexibility Theory . 13 Role of Prior Knowledge . 15 Role of Metacognition and User Control . 16 Cognitive Load Theory . 19 Human Cognitive Architecture . 20 Cognitive Load Types . 22 Split Attention . 23 Leads as a Tool to Reduce Split Attention in Hypertext . 25 Methodological Rationale . 30 Measurement of Cognitive Load . 30 Analytic Measures . 31 Subjective Measures . 31 Behavioral Measures . 32 Psychophysiological Measures . 33 Brain Activity Measures: Event-Related Potentials and Electroencephalogram . 34 Neural Oscillations and Cognitive Activity . 36 Alpha . 37 Beta . 38 Theta . 38 Event-Related Desynchronization as a Measure of Cognitive Load . 40 Localization of Cognitive Load Recording Sites . 45 Cognitive Load Measurement Hypotheses . 48 Summary . 48 Methodology . 50 Subjects . 50 Subject Identification . 50 Demographics . 51 Materials . 52
Knowledge, Attitude and Practice of Breast Cancer Screening among Female General Practitioners in Riyadh, Saudi Arabia

Background: Breast cancer has been ranked as the 1st cancer in women in Kingdom of Saudi Arabia. Screening, early detection and proper treatment of Breast Cancer was associated with more chances of better prognosis and long-term survival. The role general practitioner’s role is to provide professional knowledge, skills and support for patients as well as their caregiver about screening and prevention. This study aimed to investigate the level of knowledge of Breast Cancer risk factors, beliefs, diagnosis and practice of Breast Self Examination, Clinical Breast Examination and mammography among female General Practitioners who are currently working in primary health care center in Riyadh city, Kingdom of Saudi Arabia. Methods: A cross-sectional study was conducted using a self-administered questionnaire among female physicians, currently working as General Practitioners in Primary Health Care centers were invited. Descriptive statistics: mean, standard deviation, frequencies, percentage were calculated. Results: The majority (90%) of the respondents believed that Breast Cancer is a major health problem and 96% were aware of the importance of mammography as a screening method. But only 19% of the studied physicians requested mammogram as screening tool for women aged 40 years or more. Conclusion: The current study demonstrated that knowledge about breast cancer screening was satisfactory and highlighted the need for the provision of continuing medical education programs to improve the general practitioners' practice on cancer screening tools.
Microxarxa d'alimentació híbrida, amb suport fotovoltaic i generació dièsel, per a instal·lacions d'ús públic amb xarxa elèctrica feble

Aquest treball de fi de grau te la finalitat de dur a terme el desenvolupament d'una microxarxa hibrida, en primer lloc, es descriu el que s'enten que es una microxarxa dibrida intel·ligent aixi com el funcionament i els components essencials, comprovant l'estat de l'art d'aquesta tecnologia. Fruit que el treball esta basat en les dades aportades pel projecte Medsolar, especialment de l'hospital universitari An-Najah a Nablus, Palestina, s'explica en que va consistir aquest i les seves caracteristiques. Per tal de fer el disseny de la microxarxa es proposa una metodologia generica que despres s'aplica al cas concret de l'hospital. Amb el software Homer s'ha dut a terme el dimensionament optim de la microxarxa, ja que es una eina especialment dissenyada per a la realitzacio d'aquestes tasques. Finalment amb la voluntat de realitzar la simulacio de la microxarxa dissenyada s'ha emparat el programa Matlab-Simulink, amb especial atencio al model dels panells fotovoltaics. El treball s'ha fet amb la voluntat de mostrar l'amplitud dels coneixements i capacitats adquirides en la realitzacio del grau d'enginyeria electrica.
Rhamnolipid Surfactant Production Affects Biofilm Architecture in Pseudomonas aeruginosa PAO1

ABSTRACT In response to certain environmental signals, bacteria will differentiate from an independent free-living mode of growth and take up an interdependent surface-attached existence. These surface-attached microbial communities are known as biofilms. In flowing systems where nutrients are available, biofilms can develop into elaborate three-dimensional structures. The development of biofilm architecture, particularly the spatial arrangement of colonies within the matrix and the open areas surrounding the colonies, is thought to be fundamental to the function of these complex communities. Here we report a new role for rhamnolipid surfactants produced by the opportunistic pathogen Pseudomonas aeruginosa in the maintenance of biofilm architecture. Biofilms produced by mutants deficient in rhamnolipid synthesis do not maintain the noncolonized channels surrounding macrocolonies. We provide evidence that surfactants may be able to maintain open channels by affecting cell-cell interactions and the attachment of bacterial cells to surfaces. The induced synthesis of rhamnolipids during the later stages of biofilm development (when cell density is high) implies an active mechanism whereby the bacteria exploit intercellular interaction and communication to actively maintain these channels. We propose that the maintenance of biofilm architecture represents a previously unrecognized step in the development of these microbial communities.
The Circumorbital Bones of the Gekkota (Reptilia: Squamata)

The enormous variation of the orbit in lepidosaurs is better conceptualized in terms of composition and configuration. Broadly, the orbit varies from having totally closed rim to being open posteriorly. Two processes are responsible for changes in the components of the circumorbital series, element loss and fusion. The resulting contacts among elements are the main factors determining orbital configuration. Here, we present a revision of the gekkotan circumorbital bones in the general context of the Lepidosauria. From observations of a sample of 105 species of gekkotans prepared using different techniques, we describe the main changes in the orbit and corroborate the presence or absence of some of the ambiguous elements such as the lacrimal and the jugal. The supraorbital bones of squamates are reviewed and some problems of homology are evaluated using recent phylogenenetic hypothesis. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.
TreatYoSelf: empathy-driven behavioral intervention for marginalized youth living with HIV

Behavioral intervention technologies are well suited to addressing health behavior such as medication adherence, but only if successfully integrated into a user's daily life. Little is known about how to design such technologies to be adoptable, adaptable, useful, and feasible in everyday life. We report on the design process for TreatYoSelf, a smartphone application designed to improve medication adherence among youth living with HIV through reminders and positive reinforcement. Using participatory design, our aim was to understand factors related to adoption and acceptance of behavioral intervention technology as part of daily life. Two challenges of living with HIV led to an empathy-driven approach in our design process: (1) HIV is a stigmatized condition, which (2) disproportionately affects the marginalized populations of young African American men who have sex with men and transgender women. We discuss five empathy-driven design strategies: positive and nonjudgmental tone; minimal, avatar-based gamification; motivational and corny messages; nondisclosure through neutral signifiers; and social support through camaraderie. Our approach enabled us to identify and work through factors, often related to stigma and marginalization, which would lead to rejection of TreatYoSelf use in daily life.
The tissue micro-array as a translational research tool for biomarker profiling and validation

Abstract High-throughput molecular technologies have provided a wealth of putative biomarkers representing potential diagnostic, prognostic and therapeutic targets. Target validation commonly requires abundant and well-characterized tissue resources, as well as linked clinicopathologic data-sets. The tissue micro-array (TMA) is a validation and discovery platform of increasing popularity and necessity. TMAs provide a rapid means of examining in situ gene expression in a wide spectrum and large number of tissue samples. This paper describes the uses of TMAs as a translational research tool in biomarker profiling. The laboratory has performed numerous biomarker studies on several types of epithelial cancers. As an example, Epithelial Protein Cell Adhesion Molecule (EpCAM), a panepithelial antigen used to target tumours with immunotherapy, was examined in patients with renal cell carcinoma (RCC). EpCAM was an independent prognosticator for improved disease-specific survival in 318 clear cell RCCs examined, with a Cox proportional hazards multivariate hazard ratio of 0.63 (p=0.017; 95% confidence interval 0.43–0.92). Interestingly, despite a typically widespread epithelial expression, EpCAM is instead infrequently expressed in clear cell RCC, the most common type of renal cancer, making it a poor target for immunotherapy. In this capacity the TMA provided strong support for halting lengthy and costly clinical trials for this application.
Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases

Dipeptidyl peptidase I (DPPI) or cathepsin C is the physiological activator of groups of serine proteases from immune and inflammatory cells vital for defense of an organism. The structure presented shows how an additional domain transforms the framework of a papain‐like endopeptidase into a robust oligomeric protease‐processing enzyme. The tetrahedral arrangement of the active sites exposed to solvent allows approach of proteins in their native state; the massive body of the exclusion domain fastened within the tetrahedral framework excludes approach of a polypeptide chain apart from its termini; and the carboxylic group of Asp1 positions the N‐terminal amino group of the substrate. Based on a structural comparison and interactions within the active site cleft, it is suggested that the exclusion domain originates from a metallo‐protease inhibitor. The location of missense mutations, characterized in people suffering from Haim–Munk and Papillon–Lefevre syndromes, suggests how they disrupt the fold and function of the enzyme.
Integrin α2β1 Mediates Tyrosine Phosphorylation of Vascular Endothelial Cadherin Induced by Invasive Breast Cancer Cells*

Background: The disruption of endothelial barrier function by tumor cells was studied. Results: The attachment of tumor cells to endothelial cells leads to the disorganization of endothelial adherens junction. Conclusion: Interaction of tumor cells with endothelial cells alters endothelial signaling and facilitates cancer cell diapedesis. Significance: This study introduces new therapeutic targets for treating metastatic breast cancer. The molecular mechanisms that regulate the endothelial response during transendothelial migration (TEM) of invasive cancer cells remain elusive. Tyrosine phosphorylation of vascular endothelial cadherin (VE-cad) has been implicated in the disruption of endothelial cell adherens junctions and in the diapedesis of metastatic cancer cells. We sought to determine the signaling mechanisms underlying the disruption of endothelial adherens junctions after the attachment of invasive breast cancer cells. Attachment of invasive breast cancer cells (MDA-MB-231) to human umbilical vein endothelial cells induced tyrosine phosphorylation of VE-cad, dissociation of β-catenin from VE-cad, and retraction of endothelial cells. Breast cancer cell-induced tyrosine phosphorylation of VE-cad was mediated by activation of the H-Ras/Raf/MEK/ERK signaling cascade and depended on the phosphorylation of endothelial myosin light chain (MLC). The inhibition of H-Ras or MLC in endothelial cells inhibited TEM of MDA-MB-231 cells. VE-cad tyrosine phosphorylation in endothelial cells induced by the attachment of MDA-MB-231 cells was mediated by MDA-MB-231 α2β1 integrin. Compared with highly invasive MDA-MB-231 breast cancer cells, weakly invasive MCF-7 breast cancer cells expressed lower levels of α2β1 integrin. TEM of MCF-7 as well as induction of VE-cad tyrosine phosphorylation and dissociation of β-catenin from the VE-cad complex by MCF-7 cells were lower than in MDA-MB-231 cells. These processes were restored when MCF-7 cells were treated with β1-activating antibody. Moreover, the response of endothelial cells to the attachment of prostatic (PC-3) and ovarian (SKOV3) invasive cancer cells resembled the response to MDA-MB-231 cells. Our study showed that the MDA-MB-231 cell-induced disruption of endothelial adherens junction integrity is triggered by MDA-MB-231 cell α2β1 integrin and is mediated by H-Ras/MLC-induced tyrosine phosphorylation of VE-cad.
Oxidative Damage in the Senescence‐accelerated Mouse

ABSTRACT: The senescence‐accelerated mouse (SAM) exhibited a shortened life span (about 18 months) and early manifestation of various signs of senescence, including changes in physical activity, skin, and spinal curvature. The mechanism of senescence acceleration in SAM is thought to be related to free radical damage. Oxidative phosphorylation was estimated in liver mitochondria from SAMPS and the senescence‐resistant subtrain, SAMR1. The respiratory control ratio decreased during aging, and the ATP/O, an index of ATP synthesis, was depressed at 18 months of age in SAMPS. DNP‐dependent uncoupled respiration in liver mitochondria was markedly decreased, and active uptake of calcium was markedly dysfunctional with aging. These findings suggest that the functional disorders in mitochondria may be closely related to the shorter life span of SAMPS. White‐footed (WF) mice can live at least to 5.5 years, when some animals are still capable of reproducing and their external body condition remains healthy. The mitochondrial functions were examined in the same way as in the SAM experiments. However, no particular finding responsible for their longevity was observed in WF mice at 3 and 12 months old. More comprehensive examinations on more aged WF mice are needed for explanation of their greater longevity.
Dietary nitrate reduces resting metabolic rate: a randomized, crossover study in humans.

BACKGROUND Nitrate, which is an inorganic anion abundant in vegetables, increases the efficiency of isolated human mitochondria. Such an effect might be reflected in changes in the resting metabolic rate (RMR) and formation of reactive oxygen species. The bioactivation of nitrate involves its active accumulation in saliva followed by a sequential reduction to nitrite, nitric oxide, and other reactive nitrogen species. OBJECTIVE We studied effects of inorganic nitrate, in amounts that represented a diet rich in vegetables, on the RMR in healthy volunteers. DESIGN In a randomized, double-blind, crossover study, we measured the RMR by using indirect calorimetry in 13 healthy volunteers after a 3-d dietary intervention with sodium nitrate (NaNO₃) or a placebo (NaCl). The nitrate dose (0.1 mmol · kg⁻¹ · d⁻¹) corresponded to the amount in 200-300 g spinach, beetroot, lettuce, or other vegetable that was rich in nitrate. Effects of direct nitrite exposure on cell respiration were studied in cultured human primary myotubes. RESULTS The RMR was 4.2% lower after nitrate compared with placebo administration, and the change correlated strongly to the degree of nitrate accumulation in saliva (r² = 0.71). The thyroid hormone status, insulin sensitivity, glucose uptake, plasma concentration of isoprostanes, and total antioxidant capacity were unaffected by nitrate. The administration of nitrite to human primary myotubes acutely inhibited respiration. CONCLUSIONS Dietary inorganic nitrate reduces the RMR. This effect may have implications for the regulation of metabolic function in health and disease.
A pragmatic view of proper name reference

I argue, in this thesis, that proper name reference is a wholly pragmatic phenomenon. The reference of a proper name is neither constitutive of, nor determined by, the semantic content of that name, but is determined, on an occasion of use, by pragmatic factors. The majority of views in the literature on proper name reference claim that reference is in some way determined by the semantics of the name, either because their reference simply constitutes their semantics (which generally requires a very fine-grained individuation of names), or because names have an indexical-like semantics that returns a referent given certain specific contextual parameters. I discuss and criticize these views in detail, arguing, essentially, in both cases, that there can be no determinate criteria for reference determination—a claim required by both types of semantic view. I also consider a less common view on proper name reference: that it is determined wholly by speakers’ intentions. I argue that the most plausible version of this view—a strong neo-Gricean position whereby all utterance content is determined by the communicative intentions of the speaker—is implausible in light of psychological data. In the positive part of my thesis, I develop a pragmatic view of proper name reference that is influenced primarily by the work of Charles Travis. I argue that the reference of proper names can only be satisfactorily accounted for by claiming that reference occurs not at the level of word meaning, but at the pragmatic level, on an occasion of utterance. I claim that the contextual mechanisms that determine the reference of a name on an occasion are the same kinds of thing that determine the truth-values of utterances according to Travis. Thus, names are, effectively, occasionsensitive in the way that Travis claims predicates and sentences (amongst other expressions) are. Finally, I discuss how further research might address how my pragmatic view of reference affects traditional issues in the literature on names, and the consequences of the view for the