Miracle-dz/UniFAR-FTUs huggingface dataset:
Canadian Rheumatology Association Recommendations for the Pharmacological Management of Rheumatoid Arthritis with Traditional and Biologic Disease-modifying Antirheumatic Drugs: Part II Safety

Objective. The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of rheumatoid arthritis (RA) with traditional and biologic disease-modifying antirheumatic drugs (DMARD) in 2 parts. Part II, focusing on specific safety aspects of treatment with traditional and biologic DMARD in patients with RA, is reported here. Methods. Key questions were identified a priori based on results of a national needs-assessment survey. A systematic review of all clinical practice guidelines and consensus statements regarding treatment with traditional and biologic DMARD in patients with RA published between January 2000 and June 2010 was performed in Medline, Embase, and CINAHL databases, and was supplemented with a “grey literature” search including relevant public health guidelines. Systematic reviews of postmarketing surveillance and RA registry studies were performed to update included guideline literature reviews as appropriate. Guideline quality was independently assessed by 2 reviewers. Guideline characteristics, recommendations, and supporting evidence from observational studies and randomized trials were synthesized into evidence tables. The working group voted on recommendations using a modified Delphi technique. Results. Thirteen recommendations addressing perioperative care, screening for latent tuberculosis infection prior to the initiation of biologic DMARD, optimal vaccination practices, and treatment of RA patients with active or a history of malignancy were developed for rheumatologists, other primary prescribers of RA drug therapies, and RA patients. Conclusion. These recommendations were developed based on a synthesis of international RA and public health guidelines, supporting evidence, and expert consensus in the context of the Canadian health system. They are intended to help promote best practices and improve healthcare delivery for persons with RA.
Incident Anemia in Older Adults with Heart Failure Rate, Etiology, and Association with Outcomes.

AIMS Limited data exist on the epidemiology, evaluation, and prognosis of otherwise unexplained anemia of the elderly in HF. Thus, we aimed to determine the incidence of anemia, to characterize diagnostic testing patterns for potentially reversible causes of anemia, and to evaluate the independent association between incident anemia and long-term morbidity and mortality. METHODS AND RESULTS Within the Cardiovascular Research Network (CVRN), we identified adults age ≥65 years with diagnosed HF between 2005-2012 and no anemia at entry. Incident anemia was defined using World Health Organization (WHO) hemoglobin thresholds (<13.0 g/dL in men; <12.0 g/dL in women). All-cause death and hospitalizations for HF and any cause were identified from electronic health records. Among 38,826 older HF patients, 22,163 (57.1%) developed incident anemia over a median (interquartile range) follow-up of 2.9 (1.2, 5.6) years. The crude rate (95% Confidence Interval [CI]) per 100 person-years of incident anemia was 26.4 (CI:26.0-26.7) and was higher for preserved ejection fraction (EF) (29.2 [CI:28.6-29.8]) compared with borderline EF (26.5 [CI: 25.4-27.7]) or reduced EF (26.6 [CI: 25.8-27.4]). Iron indices, vitamin B12 level, and thyroid testing were performed in 21.8%, 14.9% and 40.2% of patients, respectively. Reduced iron stores, vitamin B12 deficiency, and/or hypothyroidism were present in 29.7%, 3.2% and 18.6% of tested patients, respectively. In multivariable analyses, incident anemia was associated with excess mortality (hazard ratio [HR] 2.14, CI:2.07-2.22) as well as hospitalization for HF (HR 1.80, CI:1.72-1.88) and any cause (HR 1.77, CI:1.72-1.83). CONCLUSION Among older adults with HF, incident anemia is common and independently associated with substantially increased risks of morbidity and mortality. Additional research is necessary to clarify the value of routine evaluation and treatment of potentially reversible causes of anemia.
Asymptotic Modeling of the Thin Film Flow with a Pressure-Dependent Viscosity

We study the lubrication process with incompressible fluid taking into account the dependence of the viscosity on the pressure. Assuming that the viscosity-pressure relation is given by the well-known Barus law, we derive an effective model using asymptotic analysis with respect to the film thickness. The key idea is to conveniently transform the governing system and then apply two-scale expansion technique.
Inhibition of N‐myristoyltransferase1 affects dengue virus replication

Dengue virus (DENV) causes dengue fever, a self‐limiting disease that could be fatal due to serious complications. No specific treatment is currently available and the preventative vaccine is only partially protective. To develop a potential drug target for dengue fever, we need to understand its biology and pathogenesis thoroughly. N‐myristoyltransferase (NMT) is an N‐terminal protein lipidation enzyme that catalyzes the covalent cotranslational attachment of fatty acids to the amino‐terminal glycine residue of a number of proteins, leading to the modulation of various signaling molecules. In this study, we investigated the interaction of dengue viral proteins with host NMT and its subsequent effect on DENV. Our bioinformatics, molecular docking, and far‐western blotting analyses demonstrated the interaction of viral envelope protein (E) with NMT. The gene expression of NMT was strongly elevated in a dependent manner during the viral replication phase in dendritic cells. Moreover, NMT gene silencing significantly inhibited DENV replication in dendritic cells. Further studies investigating the target cell types of other host factors are suggested.
Relationship between myocardial edema and regional myocardial function after reperfused acute myocardial infarction: an MR imaging study.

PURPOSE To compare the relationship of myocardial edema and corresponding contractile function over time in patients with reperfused acute myocardial infarction (AMI). MATERIALS AND METHODS This study was approved by the regional ethics committee; all patients gave written informed consent. Thirty-nine patients (34 men; mean age, 57 years; age range, 35-73 years) underwent T2-weighted, tagging, and late gadolinium enhancement magnetic resonance imaging at three time points after primary percutaneous coronary intervention for ST-elevation AMI. Circumferential strain, T2-weighted signal intensity, and volume of infarct zones, peri-infarct zones, and remote myocardium were measured. Patients were stratified by presence or absence of peri-infarct edema, defined as areas with T2-weighted signal intensity of two or more standard deviations above that of remote myocardium. Statistical analysis was performed with repeated-measures analysis of variance with post hoc Bonferroni correction. RESULTS Edematous peri-infarct myocardium had attenuated strain compared with remote myocardium at day 2 (-0.137 vs -0.226, P < .001), day 30 (-0.188 vs -0.240, P < .01), and day 90 (-0.207 vs -0.241, P = .01). Nonedematous peri-infarct myocardium had similar (P > .05) strain to remote myocardium at all time points. Strain improved in edematous peri-infarct myocardium at day 30 (P = .02) and day 90 (P < .01), closely mirroring resolution of intensity and volume of edema. Decreased strain correlated with edema volume (r = 0.30, P = .01) and normalized edema signal intensity (r = 0.28, P < .01). In eight patients with fully transmural infarction, infarct zone strain improved between day 2 and day 90 (P = .02). CONCLUSION Improvement of strain in peri-infarct myocardium closely follows regression of myocardial edema. Volume of edema and intensity of signal on T2-weighted images relate to functional recovery after reperfused AMI.
Characterization of Multipath Effects in Indoor Positioning Systems by AoA and PoA Based on Optical Signals†

In this paper, we characterize and measure the effects of the errors introduced by the multipath when obtaining the position of an agent by means of Indoor Positioning Systems (IPS) based on optical signal. These effects are characterized in Local Positioning Systems (LPSs) based on two different techniques: the first one by determining the Angle of Arrival (AoA) of the infrared signal (IR) to the detector; and the second one by working with the measurement of the Phase shift of signal Arrival from the transmitter to a receiver (PoA). We present the obtained results and conclusions, which indicate that using Position Sensitive Devices (PSD) the multipath effects for AoA have little impact on the measurement, while for PoA the positioning errors are very significant, making the system useless in many cases.
Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants

Two smyd1 paralogues, smyd1a and smyd1b, have been identified in zebrafish. Although Smyd1b function has been reported in fast muscle, its function in slow muscle and the function of Smyd1a, in general, are uncertain. In this study, we generated 2 smyd1a mutant alleles and analyzed the muscle defects in smyd1a and smyd1b single and double mutants in zebrafish. We demonstrated that knockout of smyd1a alone had no visible effect on muscle development and fish survival. This was in contrast to the smyd1b mutant, which exhibited skeletal and cardiac muscle defects, leading to early embryonic lethality. The smyd1a and smyd1b double mutants, however, showed a stronger muscle defect compared with smyd1a or smyd1b mutation alone, namely, the complete disruption of sarcomere organization in slow and fast muscles. Immunostaining revealed that smyd1a; smyd1b double mutations had no effect on myosin gene expression but resulted in a dramatic reduction of myosin protein levels in muscle cells of zebrafish embryos. This was accompanied by the up‐regulation of hsp40 and hsp90‐α1 gene expression. Together, our studies indicate that both Smyd1a and Smyd1b partake in slow and fast muscle development although Smyd1b plays a dominant role compared with Smyd1a. —Cai, M. , Han, L. , Liu, L. , He, F. , Chu, W. , Zhang, J., Tian, Z. , Du, S. Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants. FASEB J. 33, 6209–6225 (2019). www.fasebj. org
Effect of Erythropoiesis-Stimulating Agent Therapy in Patients Receiving Palliative Care of Chronic Kidney Disease

Background: Despite the increasing use of erythropoiesis-stimulating agent (ESA) in patients receiving dialysis, few studies have examined the benefits of ESA for patients with chronic kidney disease receiving palliative care. Objective: We designed a retrospective observational study to evaluate the effect of ESA in treating anemia of renal disease among adult patients receiving palliative care instead of dialysis. The primary objective was to assess whether ESA can reduce the transfusion burden and hospitalization. Results: Thirty-nine patients receiving ESA were matched with a control group of 39 patients without ESA. Their mean age and glomerular filtration rates were 76.7 (10.2) years and 11.6 (5.7) mL/min/1.73 m2, respectively. Baseline hemoglobin levels were comparable in the ESA and control groups; their corresponding values were 10.2 (1.5) and 10.1 (1.4) g/dL. During 1-year observation period, 34 units of red cell transfusion occurred in patients receiving ESA, whereas 128 units of red cell were transfused to patients in control group. Patients in the control group had higher transfusion rate (incidence rate ratio [IRR]: 3.63; 95% confidence interval [CI]: 2.49-5.31; P < .00001) and higher admission rates (IRR: 2.34; 95% CI: 1.80-3.03; P < .000001) than the ESA group even after adjustment for comorbidities. Conclusions: High disease burden of palliative care among patients with stage 4 to 5 chronic kidney disease was reflected by transfusion requirement and hospitalization rates, both of which were shown to be significantly ameliorated by ESA treatment.
Exploring the neural basis for paternal protection: an investigation of the neural response to infants in danger

Abstract Perceiving potential threat to an infant and responding to it is crucial for offspring survival and parent–child bonding. Using a combination of functional magnetic resonance imaging and multi-informant reports, this longitudinal study explores the neural basis for paternal responses to threat to infants pre-natally (N = 21) and early post-natally (n = 17). Participants viewed videos showing an infant in danger and matched control videos, while instructed to imagine that the infant was their own or someone else’s. Effects were found for infant-threatening vs neutral situations in the amygdala (region-of-interest analyses) and in clusters spanning cortical and subcortical areas (whole-brain analyses). An interaction effect revealed increased activation for own (vs unknown) infants in threatening (vs neutral) situations in bilateral motor areas, possibly indicating preparation for action. Post-natal activation patterns were similar; however, in part of the superior frontal gyrus the distinction between threat to own and unknown infant faded. Fathers showing more protective behavior in daily life recruited part of the frontal pole more when confronted with threat to their own vs an unknown infant. This exploratory study is the first to describe neural mechanisms involved in paternal protection and provides a basis for future work on fathers’ protective parenting.
Anxiety sensitivity as a moderator of the relationship between trait anxiety and illicit substance use.

Anxiety and substance use problems are common and often comorbid, and past research has shown that young adults in particular are especially at risk for developing these disorders. To further delineate the relationship between anxiety and substance use, the current study evaluated anxiety sensitivity (AS)-a cognitive vulnerability factor-as a moderator of the association between trait anxiety and illicit substance use in a large sample of young adults (N = 845; M = 18.7 years, SD = 1.0). It was hypothesized that AS would moderate the association between trait anxiety and illicit substance use, such that trait anxiety would significantly predict illicit substance use among those with high, but not low, AS. Consistent with prediction, a significant trait Anxiety × AS interaction was found, χ²(5) = 29.38, p < . 001. Specifically, analyses of simple slopes revealed that for the high-AS group, as trait anxiety increased, so did frequency of illicit substance use (odds ratio [OR] = 1.03, p = .005; 95% confidence interval [CI] [1.01, 1.06]). The slope for the low AS was not significant (OR = 0.98, p = .100; 95% CI [0.95, 1.01]). Results also showed significant moderation effects for the AS physical concerns and cognitive concerns facets but not AS social concerns. These findings suggest that AS may be an important cognitive vulnerability that may help to identify those at particular risk for substance use, and that interventions should target AS reduction in anxiety-prone individuals to reduce and prevent substance abuse.
An Advanced Strategy for Comprehensive Profiling of ADP-ribosylation Sites Using Mass Spectrometry-based Proteomics*

We augmented our MS-based proteomics strategy for the purification and identification of ADP-ribosylated peptides, through side-by-side comparison of complementary proteolytic digestions by trypsin or Lys-C, and ETD and EThcD fragmentation of precursors. This allowed us to identify an unprecedented number of ADP-ribosylated peptides (>11,000) and sites (>7000), gain insight into crosstalk between phosphorylation and ADP-ribosylation, and elucidate a spatial regulatory component in the targeting of ADP-ribosylation to distinct amino acid residue types. Graphical Abstract Highlights Comparing proteolytic digestions and precursor fragmentation methods for MS of ADPr Identification of 11,265 unique ADPr-modified peptides Mapping of hundreds of peptides co-modified by phosphorylation and ADPr ADPr modification of specific residue types displays spatial preferences ADP-ribosylation is a widespread post-translational modification (PTM) with crucial functions in many cellular processes. Here, we describe an in-depth ADP-ribosylome using our Af1521-based proteomics methodology for comprehensive profiling of ADP-ribosylation sites, by systematically assessing complementary proteolytic digestions and precursor fragmentation through application of electron-transfer higher-energy collisional dissociation (EThcD) and electron transfer dissociation (ETD), respectively. Although ETD spectra yielded higher identification scores, EThcD generally proved superior to ETD in identification and localization of ADP-ribosylation sites regardless of protease employed. Notwithstanding, the propensities of complementary proteases and fragmentation methods expanded the detectable repertoire of ADP-ribosylation to an unprecedented depth. This system-wide profiling of the ADP-ribosylome in HeLa cells subjected to DNA damage uncovered >11,000 unique ADP-ribosylated peptides mapping to >7,000 ADP-ribosylation sites, in total modifying over one-third of the human nuclear proteome and highlighting the vast scope of this PTM. High-resolution MS/MS spectra enabled identification of dozens of proteins concomitantly modified by ADP-ribosylation and phosphorylation, revealing a considerable degree of crosstalk on histones. ADP-ribosylation was confidently localized to various amino acid residue types, including less abundantly modified residues, with hundreds of ADP-ribosylation sites pinpointed on histidine, arginine, and tyrosine residues. Functional enrichment analysis suggested modification of these specific residue types is directed in a spatial manner, with tyrosine ADP-ribosylation linked to the ribosome, arginine ADP-ribosylation linked to the endoplasmic reticulum, and histidine ADP-ribosylation linked to the mitochondrion.
In vitro evaluation of barium titanate nanoparticle/alginate 3D scaffold for osteogenic human stem cell differentiation

Nanomaterials can mimic properties of extracellular matrix molecules, promising great potential for scaffold composition in tissue engineering. In the present study, we investigated whether barium titanate nanoparticles (BT NP) combined with alginate polymer would provide a new cytocompatible three-dimensional (3D) scaffold to induce osteogenic stem cell differentiation. In vitro cytocompatibility and osteogenic differentiation potential were investigated using human mesenchymal stem cells (MSC). Firstly, we studied the cell viability and oxidative stress by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) thiazolyl blue tetrazolium bromide (MTT) and superoxide dismutase (SOD) assays. Overall, neither pure BT NP or BT NP/alginate 3D scaffold induced cytotoxicity. The scanning electron and atomic force microscopy revealed that BT NP/alginate 3D scaffold produced exhibited highly interconnected pores and surface nanotopography that were favorable for MSC differentiation. Von Kossa staining showed mineralization nodules and MSCs morphology changed from spindle to cuboid shape after 21 d. Finally, BMP-2 and ALP mRNA were significantly upregulated on cells grown into the BT NP/alginate 3D scaffold. Thus, the BT NP/alginate 3D scaffold showed an osteogenic differentiation induction potential, without the addition of osteogenic supplements. These results indicate that the BT NP/alginate 3D scaffold provides a cytocompatible and bioactive microenvironment for osteogenic human MSC differentiation.
Maternal perception about child oral health is associated to child dental caries and to maternal self-report about oral health

Abstract Objective: To test the association between maternal perception about child’s oral health and child dental caries experience and maternal self-perception about oral health. Materials and methods: A cross-sectional study was performed with mothers and their children aged six to 13 years. A questionnaire was applied to mothers. Children were dentally examined using the DMF-T/dmf-t Index. For analysis, Poisson regression models with robust variance were employed for each variable of interest (child dental caries experience and maternal self-report about oral health). Magnitudes of associations were estimated through Prevalence Ratio (PR) as effect measure with 95% confidence intervals (CI). A significant level of p ≤ . 05 was adopted. Results: Overall, 131 mothers-children dyads were included. Most of children were girls (52.7%) and aged between 10 to 13 years (60.3%). Negative maternal perception about child’s oral health was associated to maternal negative self-perception about oral health (PR 2.54; 95%CI 1.54–4.30) and to higher child dental caries experience (PR 2.21; 95%CI 1.41–3.47). Conclusion: Maternal perception about child oral health was associated to child dental caries and to maternal self-report about oral health.
Sorting through chickens and eggs: a longitudinal examination of the associations between attitudes, norms, and sexual risk behavior.

OBJECTIVE Health behavior theories posit that health-relevant attitudes, beliefs, and behavioral skills drive subsequent actions people take to protect themselves from health threats. Within the realm of HIV-related sexual risk behavior, much of the research in support of this notion is cross-sectional, rather than longitudinal, particularly in studies of gay and bisexual men. Other psychological theories (e.g., self-perception or cognitive dissonance theories) suggest that the opposite could be true--that health-relevant attitudes and beliefs might change as a function of previous risk or precautionary behavior. Appreciating the complex nature of these associations is essential for modifying theory and developing appropriate interventions. DESIGN Using longitudinal data from gay and bisexual men (n = 1465), we used structural equation modeling to examine three possibilities--that perceived norms and attitudes about sexual risk would be (a) related to unprotected anal intercourse cross-sectionally, (b) related to unprotected anal intercourse at a subsequent time point, and/or (c) predicted from previous instances of unprotected anal intercourse. RESULTS Safe-sex norms and attitudes were related to unprotected anal intercourse cross-sectionally, but did not predict unprotected sex longitudinally. Rather, perceived norms and attitudes changed as a function of previous risk behavior. CONCLUSIONS These results raise the possibility that modified theoretical models might be necessary to adequately describe sexual risk behavior among gay and bisexual men.
Injury of the Spino-Thalamo-Cortical Pathway Is Necessary for Central Post-Stroke Pain

Objectives: We investigated the relationship between injury of the spino-thalamo-cortical pathway (STP) and central post-stroke pain (CPSP) in patients with intracerebral hemorrhage, using diffusion tensor tractography (DTT). Methods: 30 consecutive chronic patients, in whom integrity of the STP and the medial lemnisco-thalamo-cortical pathway (MLP) were spared in both hemispheres, were recruited. We classified the patients into two groups according to the presence of the CPSP. DTTs were obtained using the FMRIB Software Library. Fractional anisotropy (FA), mean diffusivity (MD), and tract volume were measured. A laterality index (LI) was used to determine asymmetry of DTT parameters between the hemispheres. Results: The LI for tract volume of the STP in the CPSP group was lower than that of the non-CPSP group (p = 0.000). However, there were no differences between the CPSP group and non-CPSP group for the LIs of FA or MD of the STP or for the LIs of FA, MD, or tract volume of the MLP (p > 0.05). Conclusions: Decrease of tract volume without changes in the STP FA or MD values in the CPSP group indicates partial injury of STP. Therefore, injury of the STP seems to be a requirement for the development of CPSP in patients with intracerebral hemorrhage.