Miracle-dz/UniFAR-FTUs huggingface dataset:
CpG-Oligodeoxynucleotide Inhibits Smad-Dependent Bone Morphogenetic Protein Signaling: Effects on Myeloma Cell Apoptosis and In Vitro Osteoblastogenesis

The TLR9 agonist CpG-oligodeoxynucleotide (CpG-ODN) with a phosphorothioate backbone (PTO-CpG-ODN) is evaluated in clinical trials as a vaccine adjuvant or as treatment of cancers. Bone morphogenetic proteins (BMPs) regulate growth and differentiation of several cell types, and also induce apoptosis of cancer cells. Cross-talk between BMP- and TLR-signaling has been reported, and we aimed to investigate whether CpG-ODN influenced BMP-induced osteoblast differentiation or BMP-induced apoptosis of malignant plasma cells. We found that PTO-CpG-ODN inhibited BMP-2–induced osteoblast differentiation from human mesenchymal stem cells. Further, PTO-CpG-ODN counteracted BMP-2– and BMP-6–induced apoptosis of the human myeloma cell lines IH-1 and INA-6, respectively. In contrast, PTO-CpG-ODN did not antagonize the antiproliferative effect of BMP-2 on hMSCs or IH-1 cells. Inhibition of Smad-signaling and p38 MAPK-signaling indicated that apoptosis of IH-1 cells is dependent on Smad-signaling downstream of BMP, whereas the antiproliferative effect of BMP-2 on IH-1 cells also involves p38 MAPK-signaling. Together, the data suggested a specific inhibition by PTO-CpG-ODN on BMP–Smad-signaling. Supporting this we found that PTO-CpG-ODN inhibited BMP-induced phosphorylation of receptor-Smads in human mesenchymal stem cells and myeloma cell lines. This effect appeared to be independent of TLR9 because GpC-ODN and other ODNs with the ability to form multimeric structures inhibited Smad-signaling as efficiently as PTO-CpG-ODNs, and because knockdown of TLR9 by small interfering RNA in INA-6 cells did not blunt the effect of PTO-CpG-ODN. In conclusion, our results demonstrate that PTO-CpG-ODN inhibits BMP-signaling, and thus might provoke unwanted TLR9-independent side effects in patients.
A recombinant human hyaluronidase sustained release gel for the treatment of post‐surgical edema

Edema commonly accompanies surgical procedures and when excessive, can adversely affect surgical outcomes. The skin extracellular matrix, including one of its primary components, hyaluronan (HA), is a significant barrier to effective drainage of accumulated edematous fluid. Recombinant human hyaluronidase (rHuPH20) is a human hyaluronidase that acts transiently and locally to depolymerize HA. A non‐liposomal gel formulation that provides a sustained release of rHuPH20 was tested in vivo in a preclinical murine model of acquired lymphedema.
Myosin Va Acts in Concert with Rab27a and MyRIP to Regulate Acute Von‐Willebrand Factor Release from Endothelial Cells

Von‐Willebrand factor (vWF) is a highly multimerized hemostatic glycoprotein that is stored in endothelial Weibel–Palade bodies (WPB) and secreted upon cell stimulation to act in recruiting platelets to sites of vessel injury. Only fully matured multimeric vWF represents an efficient anchor for platelets, and endothelial cells have developed mechanisms to prevent release of immature vWF. Full maturation of vWF occurs within WPB following their translocation from a perinuclear site of emergence at the trans‐Golgi network (TGN) to the cell periphery. The WPB‐associated small GTPase Rab27a is involved in restricting immature WPB exocytosis and we searched for links between Rab27a and the actin cytoskeleton that could anchor WPB inside endothelial cells until they are fully matured. We here identify myosin Va as such link. Myosin Va forms a tripartite complex with Rab27a and its effector MyRIP and depletion of or dominant‐negative interference with myosin Va leads to an increase in the ratio of perinuclear to more peripheral WPB. Concomitantly, myosin Va depletion results in an elevated secretion of less‐oligomeric vWF from histamine‐stimulated endothelial cells. These results indicate that a Rab27a/MyRIP/myosin Va complex is involved in linking WPB to the peripheral actin cytoskeleton of endothelial cells to allow full maturation and prevent premature secretion of vWF.
Convallatoxin-Induced Reduction of Methionine Import Effectively Inhibits Human Cytomegalovirus Infection and Replication

ABSTRACT Cytomegalovirus (CMV) is a ubiquitous human pathogen that increases the morbidity and mortality of immunocompromised individuals. The current FDA-approved treatments for CMV infection are intended to be virus specific, yet they have significant adverse side effects, including nephrotoxicity and hematological toxicity. Thus, there is a medical need for safer and more effective CMV therapeutics. Using a high-content screen, we identified the cardiac glycoside convallatoxin as an effective compound that inhibits CMV infection. Using a panel of cardiac glycoside variants, we assessed the structural elements critical for anti-CMV activity by both experimental and in silico methods. Analysis of the antiviral effects, toxicities, and pharmacodynamics of different variants of cardiac glycosides identified the mechanism of inhibition as reduction of methionine import, leading to decreased immediate-early gene translation without significant toxicity. Also, convallatoxin was found to dramatically reduce the proliferation of clinical CMV strains, implying that its mechanism of action is an effective strategy to block CMV dissemination. Our study has uncovered the mechanism and structural elements of convallatoxin, which are important for effectively inhibiting CMV infection by targeting the expression of immediate-early genes. IMPORTANCE Cytomegalovirus is a highly prevalent virus capable of causing severe disease in certain populations. The current FDA-approved therapeutics all target the same stage of the viral life cycle and induce toxicity and viral resistance. We identified convallatoxin, a novel cell-targeting antiviral that inhibits CMV infection by decreasing the synthesis of viral proteins. At doses low enough for cells to tolerate, convallatoxin was able to inhibit primary isolates of CMV, including those resistant to the anti-CMV drug ganciclovir. In addition to identifying convallatoxin as a novel antiviral, limiting mRNA translation has a dramatic impact on CMV infection and proliferation.
Comparison of Lipid Profile Status between Hypertensive and Normotensive People of Bangladesh

Introduction lood pressure is the force that drives blood through blood vessels to supply oxygen and nutrients to the body’s organs and tissues and carry away metabolites and waste materials. Blood pressure is optimal if the systolic blood pressure (SBP) is lower than 120mmHg and diastolic blood pressure (DBP) is less than 80mm Hg. Hypertension is one of the most common diseases treated by physicians. It is a common health problem worldwide and with ongoing global increase in the incidence. Hypertension is defined as a systolic BP ≥ 140 mm Hg and or diastolic BP ≥ 90 mm Hg. 3 Essential hypertension is a complex multifaceted disorder, which may include other abnormalities including dyslipidemia, central obesity, glucose intolerance and hyperinsulinemia.
Clinical and financial analysis of an acute palliative care unit in an oncological department

The aim of this article is to describe the clinical activity and medical intervention of an acute model of palliative care unit (APC), as well as the reimbursement procedures and economic viability. A sample of 504 patients admitted at an APC in 1 year was surveyed. Indications for admission, pain and symptom intensity, analgesic treatments, procedures, instrumental examinations and modalities of discharge were recorded. For each patient, tariff for reimbursement was calculated according to the existent disease related grouping (DRG) system. The mean age was 62 years, and 246 patients were males. The mean hospital stay was 5.4 days. Pain control was the most frequent indication for admission. All patients had laboratory tests and several instrumental examinations. Almost all patients were prescribed one or more opioids at significant doses, and different routes of administration, as well as medication as needed. 59 patients received blood cell transfusions and 34 interventional procedures. Only 40 patients died in the unit, 11 of them being sedated at the end of life. Treatment efficacy was considered optimal and mild in 264 and 226 patients respectively. A mean of 3019 euros for admission was reimbursed by the Health Care System. APCs are of paramount importance within an oncological department, as they provide effective and intensive treatments during the entire course of disease, providing a simultaneous and integrated approach. Our findings also suggest both a cost and quality incentive for oncological departments to develop APC.
Structure, dynamics and binding characteristics of the second PDZ domain of PTP-BL.

The PDZ domains of the protein tyrosine phosphatase PTP-BL mediate interactions by binding to specific amino acid sequences in target proteins. The solution structure of the second PDZ domain of PTP-BL, PDZ2, displays a compact fold with six beta strands and two alpha-helices. A unique feature of this domain compared to the canonical PDZ fold is an extended flexible loop at the base of the binding pocket, termed L1, that folds back onto the protein backbone, a feature that is shared by both the murine and human orthologues. The structure of PDZ2 differs significantly from the orthologous human structure. A comparison of structural quality indicators clearly demonstrates that the PDZ2 ensemble is statistically more reasonable than that of the human orthologue. The analysis of (15)N relaxation data for PDZ2 shows a normal pattern, with more rigid secondary structures and more flexible loop structures. Close to the binding pocket, Leu85 and Thr88 display greater mobility when compared to surrounding residues. Peptide binding studies demonstrated a lack of interaction between murine PDZ2 and the C terminus of the murine Fas/CD95 receptor, suggesting that the Fas/CD95 receptor is not an in vivo target for PDZ2. In addition, PDZ2 specifically binds the C termini of both human Fas/CD95 receptor and the RIL protein, despite RIL containing a non-canonical PDZ-interacting sequence of E-x-V. A model of PDZ2 with the RIL peptide reveals that the PDZ2 binding pocket is able to accommodate the bulkier side-chain of glutamic acid while maintaining crucial protein to peptide hydrogen bond interactions.
Bodenin: A novel murine gene expressed in restricted areas of the brain

A gene trap screen designed to isolate novel mouse genes involved in nervous system development was performed. Here, we describe the isolation and characterization of a novel gene, bodenin, which is expressed in restricted areas of the brain. β‐Galactosidase marker gene activity was detected in the embryo at the start of organogenesis (embryonic day 8.5; E8.5). Staining gradually became stronger until E12.5, when embryos exhibited widespread expression. In brains of newborn and adult mice, β‐galactosidase staining was confined predominantly to forebrain structures. Transcriptional activity was also observed in kidney, liver, lung, heart, skeletal muscle, and testes. Part of the trapped gene was isolated by 5′‐rapid amplification of cDNA ends (5′‐RACE). Isolation and sequencing of the complete cDNA revealed an unknown gene encoding a 200 amino acid protein. Comparison with published sequences showed 94% amino acid identity to a human integrin cytoplasmic domain‐associated protein. Mice homozygous for the mutation were viable and did not exhibit any obvious abnormal phenotype. However, concealed phenotypic abnormalities cannot be excluded. The lack of readily visible abnormalities may also be due to functional compensation or to the production of low levels of wild‐type protein in mice homozygous for the gene trap vector insertion. Nevertheless, the restricted expression of bodenin in the brain of newborn and adult mice suggests a role for this novel gene in the developing and mature central nervous system. Dev. Dyn. 1998;212:293–303. © 1998 Wiley‐Liss, Inc.
Evidence for association between a Toll-like receptor 4 gene polymorphism and moderate/severe periodontitis in the Japanese population.

BACKGROUND AND OBJECTIVE Chronic periodontitis is an inflammatory disease caused by bacteria in subgingival pockets. Because Toll-like receptor 2 and Toll-like receptor 4 have been shown to play an important role in the recognition of periodontal pathogens, we investigated the relevance of genetic variations in TLR2 and TLR4 to susceptibility to periodontitis. MATERIAL AND METHODS A total of 97 patients with chronic periodontitis and 100 control subjects were examined for mutations in TLR2 and TLR4. Case-control analysis was performed using individual single nucleotide polymorphisms detected during the mutation search. RESULTS The missense mutations reported previously in TLR2 (677 Arg>Trp and 753 Arg>Gln) and in TLR4 (299 Asp>Gly and 399 Thr>Ile) were not detected in 97 of the Japanese patients with chronic periodontitis or in 100 of the Japanese control subjects. Nine single nucleotide polymorphisms were identified in exons of TLR2 and TLR4. The case-control analysis revealed that the frequency of the C/C genotype at base-pair position +3725 in TLR4 was significantly higher in both the moderate and the severe periodontitis patient group than in the control group. CONCLUSION A genetic variation of TLR4 might be associated with moderate and severe periodontitis in the Japanese population.
Three-compartment wrist arthrography: correlation of pain site with location of uni- and bidirectional communications.

OBJECTIVE Our objective was twofold: (1) to determine whether the site of patients' pain correlates with abnormal findings on three-compartment wrist arthrograms and (2) to determine whether the directional nature (uni- vs bidirectional) of communication(s) between adjacent wrist joint compartments shown on three-compartment wrist arthrograms correlates with the presence and site of pain. MATERIALS AND METHODS We retrospectively studied 462 three-compartment wrist arthrograms of 458 patients. The patients were divided into four groups according to the site of pain, the correlation of that site with the site of the communication, and the directional characteristics of communications shown on the arthrogram: (1) exact correlation between site of pain and arthrographic findings, (2) correlation only between side of pain (ulnar or radial) and arthrographic findings, (3) ambiguous correlations (e.g., multifocal, midline, or diffuse pain), and (4) no correlation between site of pain and arthrographic findings. RESULTS In 191 patients (42%), 226 intercompartmental communications were detected (51 uni- or 173 bidirectional). One hundred sixty-one patients had only one communication (uni- or bidirectional), and 30 patients had more than one (uni- and/or bidirectional) communication for a total of 65 defects. Regardless of the directional nature of the communication, no positive association between sites and/or the side of symptoms and sites of communications was demonstrable. However, a potential association appears to exist between ulnar-sided pain and combined lunotriquetral and triangular fibrocartilage tears. CONCLUSION Our results suggest that the directional nature of interjoint communications has little or no clinical significance. Thus, with the exception of seeking the cause of ulnar-sided pain, our results question the usefulness of routine arthrography for correlating sites of patients' symptoms and individual interjoint communications.
Classification of Human Emotions from Electroencephalogram (EEG) Signal using Deep Neural Network

Estimation of human emotions from Electroencephalogram (EEG) signals plays a vital role in developing robust Brain-Computer Interface (BCI) systems. In our research, we used Deep Neural Network (DNN) to address EEG-based emotion recognition. This was motivated by the recent advances in accuracy and efficiency from applying deep learning techniques in pattern recognition and classification applications. We adapted DNN to identify human emotions of a given EEG signal (DEAP dataset) from power spectral density (PSD) and frontal asymmetry features. The proposed approach is compared to state-of-the-art emotion detection systems on the same dataset. Results show how EEG based emotion recognition can greatly benefit from using DNNs, especially when a large amount of training data is available.
Quantitative Validation of Media for Transportation and Storage of Streptococcus pneumoniae

ABSTRACT The need to design effective Streptococcus pneumoniae vaccines and to monitor resistance means that it is essential to have efficient methods to determine carriage rates. Two liquid media, consisting of skim milk, glycerol, glucose, and tryptone soya broth (STGG) or skim milk, glycerol, and glucose (SGG) alone, were evaluated for their ability to maintain pneumococcal viability. Optimal recovery of S. pneumoniae was achieved when swabs were transferred to STGG medium prior to plating onto blood agar-gentamicin selective plates (22%) compared to 7% when plated out directly (P < 0.0001 by Fisher's exact test). Both STGG and SGG media are appropriate for the long-term storage of pneumococci and primary swab samples at −70°C, with no decrease in viable count observed following repeated freeze-thaw cycles. Samples could be stored refrigerated for up to 3 days in either STGG or SGG medium with no significant loss of viability. Viability decreased progressively in storage at 20 to 30°C, with greater losses of viability occurring at the higher temperatures. There were no significant differences in viability between isolates in the two media. STGG preserved pneumococci significantly better (about twofold) than SGG medium at 21°C (P < 0.0001) and 30°C (P < 0.0001). Samples can be stored for 4 and 2.5 days at 6 to 8°C, 28 and 17 h at 21°C, and 15 and 7 h at 30°C in STGG and SGG media, respectively. For field studies undertaken in resource-limited environments, SGG medium can be prepared by using locally available materials. The quantitative data reported in this study will enable researchers to plan appropriate transport and storage protocols.
Poly I:C Accelerates Development of Diabetes Mellitus in Diabetes-Prone BB Rat

We developed a new experimental model of accelerated diabetes mellitus in the genetically susceptible diabetes-prone BB rat with the administration of the IFN-α inducer poly I:C. With this model, there was both an increased incidence and accelerated onset of insulin-dependent-diabetes in poly I:C–treated animals compared with saline-treated controls. All twelve rats administered poly I:C (5 μg/gm body weight 3 times/wk) developed diabetes by 57 days of age (100%) compared with 1 of 27 (3.7%) saline-treated controls. Furthermore, the development of diabetes was accelerated in the poly I:C–treated group (mean age ± SE at onset 52.8 ± 0.58 days) compared with saline-treated controls (89.3 ± 2.4 days, P < 0.01). Additionally, poly I:C–treated rats had higher mean serum IFN-α levels than saline-treated rats at weeks 2 and 3 of treatment (210 vs. 27 and 183 vs. 25 U/ml, respectively, P < 0.001). Poly I:C treatment of 5 Wistar rats, the parental strain, which is not susceptible to diabetes, did not result in insulitis, diabetes, or hyperglycemia. The histopathologic findings of insulitis and decreased immunoreactive islet insulin in poly I:C–accelerated diabetic BB rats and in BB rats with spontaneous diabetes suggest a similar pathophysiology.
Timing of Hospice Referral

In general, satisfaction with timing of hospice referral was measured in mortality follow-back surveys of patients who died in hospice. In contrast in this study, investigators assessed timing of the hospice referral in patients enrolled in hospice for a minimum of 2 weeks. About one third of patients or families identified that it would have been easier if they had started hospice earlier. Barriers to early hospice access were associated primarily with access to the health care system.
Home Is Where the Help Is

Abstract Policy regarding long-term care has been an issue of rising national concern. In this paper we examine the transition of Danish long-term care policy with special attention to Skævinge, the first community in Denmark to integrate institutional and community-based services for the elderly. Recent studies on the variation between costs and services in Danish communities and the results of U.S. studies on community-based care suggest that successful implementation of integrated institutional and community-based long-term care is feasible in the United States. Lessons from Denmark highlight conditions that will facilitate success in this endeavor.
Explaining the labour performance of immigrant women in Spain: The interplay between family, migration and legal trajectories

The labour performance of migrants has been largely assumed to vary with individuals’ reasons to migrate. Accordingly, migrants who migrate to join their relatives at destination are commonly expected to be negatively selected in terms of their labour characteristics. However, family and economic reasons for migration are not mutually exclusive but often complementary, especially among women. In addition, there exists a large variation in the post-migration employment rates of the so-called ‘family migrants’. In this article, I argue that the temporal sequence of migration and key family life-cycle events may help us in explaining the post-migration employment patterns of migrants, especially that of females. To test this hypothesis I first construct a comprehensive typology that classifies all immigrants according to the timing of marriage and migration for each spouse, and their immigrant or native origin. Next, I examine the explanatory power of this typology by estimating the employment probability of migrants in multivariate logit regressions that include the resulting types of ‘family migrants’ as independent. The obtained results confirm the theoretical and empirical utility of studying marriage and migration jointly in order to explain differences in the labour performance of immigrant women. Moreover, the main conclusions concerning cross-type differences in female labour behaviour remain valid ever after controlling for current legal status and legal status at entry, and running separate analyses for the main origin groups in Spain.
Implied volatility skews and stock return skewness and kurtosis implied by stock option prices

The Black-Scholes* option pricing model is commonly applied to value a wide range of option contracts. However, the model often inconsistently prices deep in-the-money and deep out-of-the-money options. Options professionals refer to this well-known phenomenon as a volatility 'skew' or 'smile'. In this paper, we examine an extension of the Black-Scholes model developed by Corrado and Su that suggests skewness and kurtosis in the option-implied distributions of stock returns as the source of volatility skews. Adapting their methodology, we estimate option-implied coefficients of skewness and kurtosis for four actively traded stock options. We find significantly nonnormal skewness and kurtosis in the option-implied distributions of stock returns.