Miracle-dz/UniFAR-FTUs huggingface dataset:
A Primer in Longitudinal Data Analysis

Longitudinal data, comprising repeated measurements of the same individuals over time, arise frequently in cardiology and the biomedical sciences in general. For example, Frison and Pocock1 used repeated measurements of the liver enzyme creatine kinase in serum of cardiac patients to study changes in liver function over a 12-month study period. The main goal, indeed the raison d’etre , of a longitudinal study is characterization of changes in the response of interest over time. Ordinarily, changes in the response are also related to selected covariates. For example, Frison and Pocock1 compared changes in creatine kinase between patients randomized to active drug and placebo. The past 25 years have witnessed remarkable developments in statistical methods for the analysis of longitudinal data. Despite these important advances, researchers in the biomedical sciences have been somewhat slow to adopt these methods and often rely on statistical techniques that fail to adequately account for longitudinal study designs. The goal of the present report is to provide an overview of some recently developed methods for longitudinal analyses that are more appropriate, with a focus on 2 methods for continuous responses: the analysis of response profiles and linear mixed-effects models. The analysis of response profiles is better suited to settings with a relatively small number of repeated measurements, obtained on a common set of occasions, whereas linear mixed-effects models are suitable in more general settings. Before describing these methods, we review some of the defining features of longitudinal studies and highlight the main aspects of longitudinal data that complicate their analysis. ### Covariance Structure A common feature of repeated measurements on an individual is correlation; that is, knowledge of the value of the response on one occasion provides information about the likely value of the response on a future occasion. Another common feature of longitudinal data is heterogeneous …
The molecular mechanisms of the anti-amyloid effects of phenols

Previous investigations demonstrated that various aromatic compounds, many of which are known antioxidants, inhibit amyloid fibril formation. Yet, the mechanism of action of these compounds is not fully understood and contribution of their antioxidative potency has not been addressed. In recent publications, Ono et al. (2003, 2004) studied the anti-amyloid effects of 11 phenols on each of three consecutive processes: (1) seeding (formation) of nascent fibrils, (2) elongation (extension) of the fibrils, and (3) depolymerization (destabilization) of the formed assemblies. The aim of the present study was to evaluate the molecular mechanisms that mediate the effects of the studied inhibitors on each of these processes. Hierarchical clustering analyses indicated that the studied inhibitors can be categorized into three groups: ‘slightly active’ inhibitors, ‘highly active’ inhibitors and ‘selective inhibitors’ that differ markedly in their effects on these three stages. Analyses of the correlations between the effects of the studied compounds on the various stages of amyloid fibril formation, and their known physicochemical properties provided novel insights on the specific role of hydrophobic and aromatic interactions as well as the antioxidative potency on the process of amyloid fibril formation and dissociation. Specifically, the hydrophobic and/or aromatic character of the compounds makes the major contribution to the anti-formation and anti-extension effects, whereas the antioxidative potency relates mostly to the promotion of destabilization.
MIXED EFFECTS IN STOCHASTIC DIFFERENTIAL EQUATION MODELS

† A class of statistical models is proposed where random efiects are incorporated into a stochastic difierential equations model, and an expression for the likelihood function is derived. In general, though, it is not possible to flnd an explicit expression for the likelihood function, but in a very simple example it is derived and explicit maximum likelihood estimators are found. The estimators are evaluated in a simulation study, and illustrated on dissolution data of metoprolol tartrate tablets.
Antiviral therapy in patients after treatment for hepatitis C-related hepatocellular carcinoma.

BACKGROUND/AIMS Despite great progress, antiviral treatment for chronic hepatitis C in patients with prior hepatocellular carcinoma (HCC) has been rarely investigated. We evaluated the efficacy and safety of antiviral therapy following treatment for hepatitis C-related HCC. METHODS Thirteen patients (age 34 to 60 years) who were treated with peginterferon plus ribavirin after treatment for HCC were reviewed. RESULTS There were 6 patients with genotype 1 and 7 patients with genotype 2. All patients showed advanced fibrosis (≥F3) but belonged to the Child-Pugh class A. Treatment was stopped in 2 patients because of recurrent HCC and in 1 patient due to a lack of early virologic response. Seven patients achieved sustained virologic response and three patients relapsed. The sustained virologic response rate was 54% overall, 17% in genotype 1, and 86% in genotype 2. No significant adverse events were reported. CONCLUSIONS Antiviral therapy should not be excluded in patients who were previously treated with HCC with genotype 2 chronic hepatitis C, in which an efficacious antiviral treatment for chronic hepatitis C was feasible. Additional study is needed to prove the validity of antiviral therapy in patients with genotype 1 hepatitis C-related HCC.
Assessment of the Quality of Antenatal Care Services Provided by Health Workers Using a Mobile Phone Decision Support Application in Northern Nigeria: A Pre/Post-Intervention Study

Background Given the shortage of skilled healthcare providers in Nigeria, frontline community health extension workers (CHEWs) are commonly tasked with providing maternal and child health services at primary health centers. In 2012, we introduced a mobile case management and decision support application in twenty primary health centers in northern Nigeria, and conducted a pre-test/post-test study to assess whether the introduction of the app had an effect on the quality of antenatal care services provided by this lower-level cadre. Methods Using the CommCare mobile platform, the app dynamically guides CHEWs through antenatal care protocols and collects client data in real time. Thirteen health education audio clips are also embedded in the app for improving and standardizing client counseling. To detect changes in quality, we developed an evidence-based quality score consisting of 25 indicators, and conducted a total of 266 client exit interviews. We analyzed baseline and endline data to assess changes in the overall quality score as well as changes in the provision of key elements of antenatal care. Results Overall, the quality score increased from 13.3 at baseline to 17.2 at endline (p<0.0001), out of a total possible score of 25, with the most significant improvements related to health counseling, technical services provided, and quality of health education. Conclusion These study results suggest that the introduction of a low-cost mobile case management and decision support application can spur behavior change and improve the quality of services provided by a lower level cadre of healthcare workers. Future research should employ a more rigorous experimental design to explore potential longer-term effects on client health outcomes.
Exploring 3D manipulation on large stereoscopic displays

In the last years stereoscopic 3D has seen a drastic increase in popularity especially in terms of consumer-ready hardware and software. While the technology for input (smart-phone, Kinect, etc.) as well as output (passive/active stereoscopic and auto-stereoscopic displays etc.) is market ready, only few solutions for natural interaction with such devices exist. In this paper we propose an approach for mobile and gestural interaction with stereoscopic 3D content. We evaluate our technique in a 3D docking task on a large 3D display. In an experiment the interaction technique was evaluated for monoscopic and stereoscopic displayed data. Our results show that the translation and rotation precision benefits from the usage of stereoscopic 3D. Especially for tasks that require simultaneous rotation on all three axes stereoscopic displays outperform monoscopic 3D drastically.
Phenylalanine 169 in the Second Extracellular Loop of the Human Histamine H4 Receptor Is Responsible for the Difference in Agonist Binding between Human and Mouse H4 Receptors

Using the natural variation in histamine H4 receptor protein sequence, we tried to identify amino acids involved in the binding of H4 receptor agonists. To this end, we constructed a variety of chimeric human-mouse H4 receptor proteins to localize the domain responsible for the observed pharmacological differences between human and mouse H4 receptors in the binding of H4 receptor agonists, such as histamine, clozapine, and VUF 8430 [S-(2-guanidylethyl)-isothiourea]. After identification of a domain between the top of transmembrane domain 4 and the top of transmembrane domain 5 as being responsible for the differences in agonist affinity between human and mouse H4Rs, detailed site-directed mutagenesis studies were performed. These studies identified Phe169 in the second extracellular loop as the single amino acid responsible for the differences in agonist affinity between the human and mouse H4Rs. Phe169 is part of a Phe-Phe motif, which is also present in the recently crystallized β2-adrenergic receptor. These results point to an important role of the second extracellular loop in the agonist binding to the H4 receptor and provide a molecular explanation for the species difference between human and mouse H4 receptors.
Optimized design of medium frequency transformers with high isolation requirements

For future DC electric power systems, high-power DC-DC converters will play a major role as they will substitute today's bulky 50/60Hz transformers. One key component within this DC-DC converters is the medium frequency transformer that provides the isolation level and the step up/down of the different voltage levels. As a consequence, an optimized design methodology that considers this high isolation requirements is needed. This paper presents a step-by-step design for medium frequency transformers with high isolation requirements. Each step in the design is carefully discussed and the required design considerations, such as flux density limits, isolation and thermal management, are explained in detail. The proposed design procedure is applied to a core-type transformer analyzing the outcome of the optimization process.
Comparative study of tissue reactions to calcium phosphate ceramics among cancellous, cortical, and medullar bone sites in rabbits.

In order to understand the influence of the implantation site on bone biomaterial evaluation, we implanted cylinders of HA and beta-TCP ceramics in the femoral diaphysis and condyle of rabbits. After 3, 8, 12, and 24 weeks of implantation, histological investigation and histomorphometry were performed on undecalcified samples. Our results show that spontaneous bone healing in the empty cavities is significantly different (p < 0.05) between cortical (SBH > 80%) and cancellous bone sites (SBH < 31%) and that no new bone is formed in marrow tissue. For both porous ceramics, the highest osteogenesis was obtained in the cortical site. Osteogenesis was intermediate in the cancellous site and weak in the medullar site. The material biodegradation was the strongest in the medullar site and higher in the cancellous site than in the cortical site. Both activities were better in the beta-TCP than in the HA (p > 0.05). The marrow tissue presents a foreign-body reaction more reliable, sensitive, and durable than other bone tissues. Therefore, the cancellous bone site is a good site for evaluation of the biofunctionality of biomaterials because of the equilibrium of the osteogenesis and the biodegradation activities, but marrow tissue seems to be better for testing material biocompatibility in vivo.
Serum Levels of Progranulin Are Closely Associated with Microvascular Complication in Type 2 Diabetes

Objective. Progranulin (PGRN) was recently introduced as a novel marker of chronic inflammatory response in obesity and type 2 diabetes capable of directly affecting the insulin signaling pathway. This study aimed to investigate the correlation between PGRN and type 2 diabetics with microvascular complications. Methods. PGRN serum levels and glucose metabolism related substance were measured in 84 type 2 diabetic patients with or without microangiopathies and 12 health persons. Further analyses of serum PGRN in different stages of diabetic microangiopathies were conducted. Results. Serum levels of PGRN were markedly higher in type 2 diabetic patients with microangiopathies. PGRN serum levels increased with the progress of diabetic microangiopathies with significantly highest values detectable in clinical diabetic nephropathy (CDN) and proliferative diabetic retinopathy (PDR) groups. Serum PGRN concentrations in all individuals positively and markedly correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), triglyceride (TG), urinary albumin excretion rate (UAER), blood urea nitrogen (BUN), creatinine (CRE), white blood cell (WBC), disease duration, IL-6, and TNF-α, while correlating negatively and significantly with eGFR. Multiple linear regression analysis showed that only UAER and CRE were independently associated with serum PGRN. Conclusion. PGRN might be considered as a marker for diabetic microangiopathy and its severity.
Integration and scaling of UV‐B radiation effects on plants: from molecular interactions to whole plant responses

Abstract A process based model integrating the effects of UV‐B radiation to molecular level processes and their consequences to whole plant growth and development was developed from key parameters in the published literature. Model simulations showed that UV‐B radiation induced changes in plant metabolic and/or photosynthesis rates can result in plant growth inhibitions. The costs of effective epidermal UV‐B radiation absorptive compounds did not result in any significant changes in plant growth, but any associated metabolic costs effectively reduced the potential plant biomass. The model showed significant interactions between UV‐B radiation effects and temperature and any factor leading to inhibition of photosynthetic production or plant growth during the midday, but the effects were not cumulative for all factors. Vegetative growth were significantly delayed in species that do not exhibit reproductive cycles during a growing season, but vegetative growth and reproductive yield in species completing their life cycle in one growing season did not appear to be delayed more than 2–5 days, probably within the natural variability of the life cycles for many species. This is the first model to integrate the effects of increased UV‐B radiation through molecular level processes and their consequences to whole plant growth and development.
Low-radio-frequency eclipses of the redback pulsar J2215+5135 observed in the image plane with LOFAR.

The eclipses of certain types of binary millisecond pulsars (i.e. 'black widows' and 'redbacks') are often studied using high-time-resolution, 'beamformed' radio observations. However, they may also be detected in images generated from interferometric data. As part of a larger imaging project to characterize the variable and transient sky at radio frequencies <200 MHz, we have blindly detected the redback system PSR J2215+5135 as a variable source of interest with the Low-Frequency Array (LOFAR). Using observations with cadences of two weeks - six months, we find preliminary evidence that the eclipse duration is frequency dependent (∝ν-0.4), such that the pulsar is eclipsed for longer at lower frequencies, in broad agreement with beamformed studies of other similar sources. Furthermore, the detection of the eclipses in imaging data suggests an eclipsing medium that absorbs the pulsed emission, rather than scattering it. Our study is also a demonstration of the prospects of finding pulsars in wide-field imaging surveys with the current generation of low-frequency radio telescopes.
Noninvasive Dynamic Imaging of Tumor Early Response to Nanoparticle-mediated Photothermal Therapy

In spite of rapidly increasing interest in the use of nanoparticle-mediated photothermal therapy (PTT) for treatment of different types of tumors, very little is known on early treatment-related changes in tumor response. Using graphene oxide (GO) as a model nanoparticle (NP), in this study, we tracked the changes in tumors after GO NP-mediated PTT by magnetic resonance imaging (MRI) and quantitatively identified MRI multiple parameters to assess the dynamic changes of MRI signal in tumor at different heating levels and duration. We found a time- and temperature-dependent dynamic change of the MRI signal intensity in intratumor microenvironment prior to any morphological change of tumor, mainly due to quick and effective eradication of tumor blood vessels. Based on the distribution of GO particles, we also demonstrated that NP-medited PTT caused heterogeneous thermal injury of tumor. Overall, these new findings provide not only a clinical-related method for non-invasive early tracking, identifying, and monitoring treatment response of NP-mediated PTT but also show a new vision for better understanding mechanisms of NP-mediated PTT.
Dendritic Cell Mediated Delivery of Plasmid DNA Encoding LAMP/HIV-1 Gag Fusion Immunogen Enhances T Cell Epitope Responses in HLA DR4 Transgenic Mice

This report describes the identification and bioinformatics analysis of HLA-DR4-restricted HIV-1 Gag epitope peptides, and the application of dendritic cell mediated immunization of DNA plasmid constructs. BALB/c (H-2d) and HLA-DR4 (DRA1*0101, DRB1*0401) transgenic mice were immunized with immature dendritic cells transfected by a recombinant DNA plasmid encoding the lysosome-associated membrane protein-1/HIV-1 Gag (pLAMP/gag) chimera antigen. Three immunization protocols were compared: 1) primary subcutaneous immunization with 1×105 immature dendritic cells transfected by electroporation with the pLAMP/gag DNA plasmid, and a second subcutaneous immunization with the naked pLAMP/gag DNA plasmid; 2) primary immunization as above, and a second subcutaneous immunization with a pool of overlapping peptides spanning the HIV-1 Gag sequence; and 3) immunization twice by subcutaneous injection of the pLAMP/gag DNA plasmid. Primary immunization with pLAMP/gag-transfected dendritic cells elicited the greatest number of peptide specific T-cell responses, as measured by ex vivo IFN-γ ELISpot assay, both in BALB/c and HLA-DR4 transgenic mice. The pLAMP/gag-transfected dendritic cells prime and naked DNA boost immunization protocol also resulted in an increased apparent avidity of peptide in the ELISpot assay. Strikingly, 20 of 25 peptide-specific T-cell responses in the HLA-DR4 transgenic mice contained sequences that corresponded, entirely or partially to 18 of the 19 human HLA-DR4 epitopes listed in the HIV molecular immunology database. Selection of the most conserved epitope peptides as vaccine targets was facilitated by analysis of their representation and variability in all reported sequences. These data provide a model system that demonstrates a) the superiority of immunization with dendritic cells transfected with LAMP/gag plasmid DNA, as compared to naked DNA, b) the value of HLA transgenic mice as a model system for the identification and evaluation of epitope-based vaccine strategies, and c) the application of variability analysis across reported sequences in public databases for selection of historically conserved HIV epitopes as vaccine targets.
Household water treatment uptake during a public health response to a large typhoid fever outbreak in Harare, Zimbabwe.

Locally manufactured sodium hypochlorite (chlorine) solution has been sold in Zimbabwe since 2010. During October 1, 2011-April 30, 2012, 4,181 suspected and 52 confirmed cases of typhoid fever were identified in Harare. In response to this outbreak, chlorine tablets were distributed. To evaluate household water treatment uptake, we conducted a survey and water quality testing in 458 randomly selected households in two suburbs most affected by the outbreak. Although 75% of households were aware of chlorine solution and 85% received chlorine tablets, only 18% had reportedly treated stored water and had the recommended protective level of free chlorine residuals. Water treatment was more common among households that reported water treatment before the outbreak, and those that received free tablets during the outbreak (P < 0.01), but was not associated with chlorine solution awareness or use before the outbreak (P > 0.05). Outbreak response did not build on pre-existing prevention programs.
Commitment in organizations: Accumulated wisdom and new directions.

Series Foreword. Preface. Part 1. The Meaning and Relevance of Commitment. H.J. Klein, J.C. Molloy, J.T. Cooper, Conceptual Foundations: Construct Definitions and Theoretical Representations of Workplace Commitment. J.P. Meyer, Commitment in a Changing World of Work. M. Riketta, R.Van Dick, Commitment's Place in the Literature. Part 2. Multiple Foci of Commitment. C. Vandenberghe, Organizational Commitments. T.E. Becker, Interpersonal Commitments. M.J. Neubert, C. Wu, Action Commitments. Part 3. Building and Maintaining Commitments. M.E. Bergman, J.K. Benzer, J.B. Henning, The Role of Individual Differences as Contributors to the Development of Commitment. S.J. Wayne, J.A-M. Coyle-Shapiro, R. Eisenberger, R.C. Liden, D.M. Rousseau, L.M. Shore, Social Influences. P.M. Wright, R. Kehoe, Organizational Level Antecedents and Consequences of Commitment. S.A. Wasti, C. OEnder, Commitment across Cultures: Progress, Pitfalls and Propositions. Part 4. Methodological Issue and Challenges. S. Jaros, Measurement of Commitment. R.J. Vandenberg, L.J. Stanley, Statistical and Methodological Challenges for Commitment Researchers: Issues of Invariance, Change Across Time, and Profile Differences. Part 5. Integration and Future Directions. T.E. Becker, H.J. Klein, J.P. Meyer, Accumulated Wisdom and New Directions for Workplace Commitments.
The epidemiology of rubella disease in Ethiopia: data from the measles case-based surveillance system.

BACKGROUND Rubella is usually a mild rash illness. However, when a woman contracts rubella early in pregnancy, serious consequences may occur, including birth defects known as congenital rubella syndrome (CRS). Information is limited on the epidemiology of rubella and CRS in Ethiopia. METHOD Rubella cases reported through the measles case-based surveillance system during 2004-2009 were analyzed. RESULTS A total of 8212 samples were tested for rubella immunoglobulin (Ig) M, and 992 (12.1%) of these specimens had test results that were positive for rubella IgM. The age distribution of patients with rubella-positive cases ranged from 3 months to 44 years. The majority (94.7%) of the cases were in individuals <15 years of age. The proportion of positive specimens from urban areas (19.4%) was higher than that from rural areas (11.6%). CONCLUSIONS Rubella is endemic in Ethiopia and mainly occurs among children and young adolescents. To better understand the burden of rubella and CRS, and to develop a national strategy for rubella control in Ethiopia, CRS surveillance will need to be established, and appropriate studies need to be conducted.