Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetics of cytokine production in experimental systemic lupus erythematosus: involvement of T helper cell 1/T helper cell 2-type cytokines in disease.

We followed cytokine production from induction through disease progression in a murine model of experimental systemic lupus erythematosus (SLE). SLE was induced by immunization with the human monoclonal anti-DNA Ab that bears the common Id designated 16/6 Id. BALB/c and C3H.SW mice that are susceptible to SLE induction and C57BL/6 mice that are resistant were immunized with the 16/6 Id. Cytokine production was tested periodically for 7 mo. Increased production of IL-2 and IFN-gamma, the Th1-type cytokines, was detected in BALB/c and C3H.SW mice 2 to 4 mo following immunization. IL-4 and IL-10, the Th2-type cytokines predominated later in disease course, and peaked 5 mo following disease induction. At this stage the Th1 type cytokines dropped to levels below those observed in controls. IL-4 production also dropped rapidly to very low levels, while IL-10 production decreased but remained above control levels. The ratio of IgG2a/IgG1 of DNA and 16/6 Id-specific Abs peaked at 2 mo following disease induction and decreased later, in concordance with the higher production of Th2-type cytokines. Thus, the development of experimental SLE in mice involves two stages: increased production of Th1-type, followed by increased induction of Th2-type cytokines. High levels of the proinflammatory cytokines, TNF-alpha and IL-1, were maintained throughout disease course. No significant changes were detected in the cytokine profile of C57BL/6 immunocytes following immunization with the 16/6 Id, supporting the possible role of the cytokine network in SLE.
Interaction with the Na,K-ATPase and Tissue Distribution of FXYD5 (Related to Ion Channel)*

FXYD5 (related to ion channel, dysadherin) is a member of the FXYD family of single span type I membrane proteins. Five members of this group have been shown to interact with the Na,K-ATPase and to modulate its properties. However, FXYD5 is structurally different from other family members and has been suggested to play a role in regulating E-cadherin and promoting metastasis (Ino, Y., Gotoh, M., Sakamoto, M., Tsukagoshi, K., and Hirohashi, S. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 365–370). The goal of this study was to determine whether FXYD5 can modulate the Na,K-ATPase activity, establish its cellular and tissue distribution, and characterize its biochemical properties. Anti-FXYD5 antibodies detected a 24-kDa polypeptide that was preferentially expressed in kidney, intestine, spleen, and lung. In kidney, FXYD5 resides in the basolateral membrane of the connecting tubule, the collecting tubule, and the intercalated cells of the collecting duct. However, there is also labeling of the apical membrane in long thin limb of Henle's loop. FXYD5 was effectively immunoprecipitated by antibodies to the α subunit of Na,K-ATPase and the anti-FXYD5 antibody immunoprecipitates α. Co-expressing FXYD5 with the α1 and β1 subunits of the Na,K-ATPase in Xenopus oocytes elicited a more than 2-fold increase in pump activity, measured either as ouabain-blockable outward current or as ouabain-sensitive 86Rb+ uptake. Thus, as found with other FXYD proteins, FXYD5 interacts with the Na,K-ATPase and modulates its properties.
Inter-Quantile Ranges and Volatility of Financial Data

We propose to estimate the variance of a time series of financial returns through a quantile autoregressive model (QAR) and demonstrate that the return QAR model contains all information that is commonly captured in two separate equations for the mean and variance of a GARCH-type model. In particular, QAR allows to characterize the entire distribution of returns conditional on a positive or negative return of any given size. We show theoretically and in an empirical application that the inter-quantile range spanned by conditional quantile estimates identifies the asymmetric response of volatility to lagged returns, resulting in broader conditional densities for negative returns than for positive returns. Finally, we estimate the conditional variance based on the estimated conditional density and illustrate its accuracy with an evaluation of Value-at-Risk and variance forecasts.
RUS skeletal maturity of children in Beijing

Background: RUS (radius–ulna–short bones) maturity of children has been estimated in two provinces in China, but not in the capital. In order to obtain a clearer picture of skeletal maturity in China, it is indispensable to include children from Beijing in the study. Aim: The aims of this study were three-fold: (1) to establish RUS skeletal maturity of children in Beijing, (2) to compare RUS skeletal maturity in Beijing with the Tanner–Whitehouse 3 (TW3) standard and the Tokyo standard, and (3) to examine regional variation in skeletal maturity in China. Methods: Hand and wrist radiographs of 631 boys and 642 girls, aged 6–18, were obtained in Beijing in 1997, and their RUS skeletal maturity was estimated using the TW3 method. Results: RUS maturity of the Beijing children was very similar to the TW3 standard until the age of 10 years in the girls, and the age of 12 years in the boys. The girls attained full maturity at 15 years of age, matching the TW3 and Tokyo standards, while the boys reached full maturity at the age of 16 years, as in Tokyo boys, but 1 year earlier than the TW3 standards. Beijing children showed progressively more rapid bone maturation than the Harbin and Changsha children, and attained full maturation 1 year earlier, in both girls and boys. Conclusion: The RUS maturity of the Beijing children was comparable with that of Tokyo children, except for the boys between 11 and 13 years. Variability of the RUS maturation among the Chinese children was greater than that found among the TW3, Tokyo and Beijing children.
Qualitative and quantitative salivary changes and subjective oral dryness among patients with thyroid dysfunction

Context: There is a paucity of literature regarding the effects of thyroid disorders on the oral cavity by influencing the salivary gland function. Aims: This study aims to understand the qualitative and quantitative changes that thyroid disorder can cause in the salivary function. Settings and Design: After obtaining ethical clearance, 46 consecutive newly diagnosed thyroid dysfunction patients were enrolled in this cross-sectional study, along with 45 age-and sex-matched controls. Subjects and Methods: Unstimulated and stimulated salivary flow rates, pH, and buffering capacity of the whole saliva were studied in addition to subjective oral dryness in the study participants. Statistical Analysis Used: The independent t-test was employed to compare the means between the two groups and Pearson's Chi-square test was used to assess the goodness of fit. Results: The findings showed that females are more affected with thyroid disorders and that hypothyroidism is more commonly reported than hyperthyroidism. A significant reduction in the salivary flow rates and buffering capacity was observed among the affected group compared to the controls, whereas the salivary pH did not show significant differences between genders and also between the case and control groups. A feeling of subjective oral dryness was perceived by many affected patients. Conclusions: The study was able to establish an association between thyroid dysfunction and salivary gland function. We hope that this study leads to more high-impact research in this field as salivary diagnostics is gaining more popularity with every passing day.
Cognitive intervention for community‐dwelling older persons with memory problems: telemedicine versus face‐to‐face treatment

Memory complaints and decline in cognitive function are common in the elederly. Cognitive intervention has been shown to be beneficial in Alzheimer's disease (AD). However, few community‐based cognitive intervention programs are available in Hong Kong. The aim of this project is to examine and compare the feasibility, acceptability, and clinical outcome of a cognitive intervention program for older patients with mild cognitive impairment and mild dementia using telemedicine versus a conventional face‐to‐face method.
Matrix metalloproteinases and their inhibition in periodontal treatment.

Matrix metalloproteinases (MMPs), produced by both infiltrating and resident cells of the periodontium, play a role in physiologic (e.g., tooth eruption) and pathologic (e.g., periodontitis) events. The evidence for the role of MMPs in periodontal destruction has accumulated over three and a half decades, and it is now recognized that an imbalance between activated MMPs and their endogenous inhibitors leads to pathologic breakdown of the extracellular matrix during periodontitis. This understanding has stimulated the search for a number of synthetic inhibitors that could be used as potential therapeutic agents. Tetracycline analogues, as proteinase inhibitors, are currently closer to being used clinically than any other agents in periodontal therapy. Other MMP inhibitors, such as Batimastat (British Bio-technology, Oxford, UK), are currently being tested clinically for inhibition of cancer metastasis and other diseases. Multiple mechanisms of MMP inhibition by tetracycline analogues have been proposed. The nonantimicrobial chemically modified tetracyclines are potent inhibitors of MMPs, preventing collagen breakdown and alveolar bone loss in animal models of periodontitis. In addition, nonantimicrobial low doses of the commercially available semisynthetic tetracycline doxycycline, have been used in human clinical trails to reduce MMP activity in the gingival crevicular fluid and gingival tissues, with a resultant reduction in pocket depth and attachment loss. Of particular interest, periodontal research on the nonantimicrobial properties of tetracycline has generated new therapeutic approaches to a variety of medical disorders characterized by excess MMP activity.
Excessively crying infant in the family: mother-infant, father-infant and mother-father interaction.

METHOD We studied mother-infant, father-infant and mother-father interaction in 32 families with an excessively crying infant and in 30 control families. The group with excessive criers was divided further into subgroups of severe colic (n=13) and moderate colic (n=19). The three dyads of the family were video-recorded when the infants were an average of 5 weeks old. The assessment was carried out during the infant's feeding, nappy change and discussion between the parents. During the assessment, only four infants were crying. The Parent Child Early Relational Assessment Scale and the Beavers Scale were used. RESULTS The main findings suggest that both parents of colicky infants had less optimal parent-child interaction compared with the control parents. The problems in the interaction were most pronounced between the fathers and infants in the severe colic group. The father-infant interaction was less optimal in 13 items of 65 (20%) in the severe colic group, in one item of 65 (2%) in the moderate colic group and in none of the items in the control group. The mother-infant interaction was less optimal in six items out of 65 (9%) in the severe colic group, in three items out of 65 (5%) in the moderate colic, and in none of the items in the control group. Severely colicky infants were also less competent in interacting with their parents. In addition, interaction between the parents was more often dysfunctional in the severe colic group. CONCLUSIONS The problems in early family interaction may threaten the well-being of families with excessively crying infants and they therefore deserve special attention from the health care professionals.
Piling Pills? Forward-Looking Behavior and Stockpiling of Prescription Drugs

This paper provides evidence of forward-looking behavior in the demand for prescription drugs, while relying on registry-based, individual-level information about the universe of Danish prescription drug purchases from 1995–2014. We exploit a universal shift in policy in early 2000 from a flat-rate to a non-linear insurance plan for prescription drugs that incentivizes stockpiling at the end of the coverage year. We extend the original framework of Keeler et al. (1977) and discuss how the institutional features of most health insurance contracts, at least theoretically, incentivize intertemporal substitution in purchases across coverage years. We describe how consumers react to the introduction of the non-linear plan by increasing spending by 80% immediately before the implementation of the new regime. Next, our main analysis takes advantage of the policy experiment to formally analyze behavior immediately prior to the end-of-year reset in the non-linear plan using a difference-in-difference strategy. We provide evidence that consumers react to this reset by stockpiling toward the end of the coverage year: consumers buy what amounts to an additional 20%. We detect heterogeneity in the size of the response by individual-level characteristics, proxies for health status, and drug type. We find no evidence of any immediate adverse health utilization effects associated with the stockpiling. We round off the paper with an analysis of the importance of stockpiling for estimates of price sensitivity. We find that ignoring intertemporal substitution across coverage years inflates price sensitivity estimates by a non-negligible amount.
β-2 microglobulin level is negatively associated with global left ventricular longitudinal peak systolic strain and left atrial volume index in patients with chronic kidney disease not on dialysis

Objective: There are many factors related to high left atrial volume index (LAVI) and global left ventricular longitudinal peak systolic strain (GLS-%) decline in chronic kidney disease. The purpose of our study is to investigate the relation between the β-2 microglobulin (β-2µ) and GLS-% and LAVI in patients with chronic kidney disease not yet on dialysis. Methods: Our study was a non-randomized, controlled, prospective study. We included 87 consecutive patients with eGFR levels below 60 ml/min/m2 not on dialysis and 82 normal healthy individuals with complaints of atypical chest pain and negative stress tests as control group in our study. Patients with hospitalization related to dialysis or heart failure attacks within 3 months, active malignancy, malnutrition, pregnancy, and uncontrolled hypertension were excluded. Brachial pulse wave velocity (PWV), augmentation index, augmentation pressure and central hemodynamics, and PWV analysis were performed in order to assess the arterial stiffness and blood pressure. According to the distribution of data, Spearman and Pearson correlations and multiple linear regression were used to determine significant and independent factor associated with high LAVI and low GLS-%. Results: There were significant correlations between β-2µ with LAVI (r=0.313, p=0.004) and with GLS-% (r=–0.222, p=0.04). In multiple linear regression, the relationship between β-2µ with GLS-% [β=–0.037, 95% CI (–0.062, –0.013), p=0.004] and LAVI [β=4.522, 95% CI (2.806, 6.238), p<0.001] was independent of age, PWV, central and peripheral blood pressures, parathormone, CalciumXPhospor, Hgb levels, and eGFR. Conclusion: Increasing β-2µ levels were found to be associated with increased LAVI and decreased GLS-%. Additional experimental studies are needed to clarify these relationships.
What surgical resection margins are required to achieve oncological control in men with primary penile cancer?

To evaluate the surgical excision margin required for local oncological control in primary penile cancers, as patients with penile cancer who undergo radical amputation suffer marked psychological, functional and cosmetic sequelae, and although organ‐sparing surgery has improved the quality of life of these men, the optimum surgical excision margin to achieve oncological control is unknown.
Presenilin Proteins Undergo Heterogeneous Endoproteolysis between Thr291and Ala299and Occur as Stable N- and C-Terminal Fragments in Normal and Alzheimer Brain Tissue

Humans inheriting missense mutations in the presenilin (PS)1 and -2 genes undergo progressive cerebral deposition of the amyloid beta-protein at an early age and develop a clinically and pathologically severe form of familial Alzheimer's disease (FAD). Because PS1 mutations cause the most aggressive known form of AD, it is important to elucidate the structure and function of this multitransmembrane protein in the brain. Using a panel of region-specific PS antibodies, we characterized the presenilin polypeptides in mammalian tissues, including brains of normal, AD, and PS1-linked FAD subjects, and in transfected and nontransfected cell lines. Very little full-length PS1 or -2 was detected in brain and untransfected cells; instead the protein occurred as a heterogeneous array of stable N- and C-terminal proteolytic fragments that differed subtly among cell types and mammalian tissues. Sequencing of the major C-terminal fragment from PS1-transfected human 293 cells showed that the principal endoproteolytic cleavage occurs at and near Met298 in the proximal portion of the large hydrophilic loop. Full-length PS1 in these cells is quickly turned over (T1/2 approximately 60 min), in part to the two major fragments. The sizes and amounts of the PS fragments were not significantly altered in four FAD brains with the Cys410Tyr PS1 missense mutation. Our results indicate that presenilins are rapidly processed to N- and C-terminal fragments in both neural and nonneural cells and that interference with this processing is not an obligatory feature of FAD-causing mutations.
Advanced High Torque Density PM Vernier Machine With Multiple Working Harmonics

In recent years, permanent magnet (PM) vernier machines have gained more and more attention due to their high torque density and simple mechanical structure. However, PM vernier (PMV) machines with lap windings always suffer from long end winding length, and regular nonoverlapping winding may result in torque reduction for PMV machines. In this paper, an advanced PMV machine topology with multiple working harmonics is proposed. With specially designed stator auxiliary teeth, this topology could achieve ∼20% higher torque density than that of a regular nonoverlapping winding PMV machine, with the same magnet usage. Through finite element algorithm and theoretical analysis, the production of additional flux density harmonics and their contributions to back-electromotive force (EMF) are verified. Moreover, the electromagnetic performances of this novel machine topology, such as back-EMF and output torque, are quantitatively investigated with the geometric parameters’ effect considered. Finally, analysis results are verified by experimental test on a 21 Nm prototype, which is designed to have similar volume and weight with a 14 Nm regular commercial PM machine.
Rhes, a Striatal-selective Protein Implicated in Huntington Disease, Binds Beclin-1 and Activates Autophagy*

Background: The striatal-specific protein Rhes is implicated in the selective pathology of HD. Results: Rhes binds Beclin-1 and activates autophagy, a lysosomal degradation pathway critical in aging and neurodegeneration. Conclusion: Rhes-induced autophagy occurs independent of mTOR and JNK-1 signaling and is inhibited by huntingtin. Significance: The restricted expression of Rhes and its effect on autophagy may explain the selective striatal pathology and delayed onset of HD. The protein mutated in Huntington disease (HD), mutant huntingtin (mHtt), is expressed throughout the brain and body. However, the pathology of HD is characterized by early and dramatic destruction selectively of the striatum. We previously reported that the striatal-specific protein Rhes binds mHtt and enhances its cytotoxicity. Moreover, Rhes-deleted mice are dramatically protected from neurodegeneration and motor dysfunction in mouse models of HD. We now report a function of Rhes in autophagy, a lysosomal degradation pathway implicated in aging and HD neurodegeneration. In PC12 cells, deletion of endogenous Rhes decreases autophagy, whereas Rhes overexpression activates autophagy. These effects are independent of mTOR and opposite in the direction predicted by the known activation of mTOR by Rhes. Rhes robustly binds the autophagy regulator Beclin-1, decreasing its inhibitory interaction with Bcl-2 independent of JNK-1 signaling. Finally, co-expression of mHtt blocks Rhes-induced autophagy activation. Thus, the isolated pathology and delayed onset of HD may reflect the striatal-selective expression and changes in autophagic activity of Rhes.
The role of topoisomerase II beta on breakage and proximity of RUNX1 to partner alleles RUNX1T1 and EVI1

Rearrangements involving the RUNX1 gene account for approximately 15% of balanced translocations in therapy‐related acute myeloid leukemia (t‐AML) patients and are one of the most common genetic abnormalities observed in t‐AML. Drugs targeting the topoisomerase II (TOP2) enzyme are implicated in t‐AML; however, the mechanism is not well understood and to date a single RUNX1‐RUNX1T1 t‐AML breakpoint junction sequence has been published. Here we report an additional five breakpoint junction sequences from t‐AML patients with the RUNX1‐ RUNX1T1 translocation. Using a leukemia cell line model, we show that TOP2 beta (TOP2B) is required for induction of RUNX1 chromosomal breaks by the TOP2 poison etoposide and that, while TOP2 alpha (TOP2A) and TOP2B proteins are both present on RUNX1 and RUNX1T1 chromatin, only the TOP2B enrichment reached significance following etoposide exposure at a region on RUNX1 where translocations occur. Furthermore, we demonstrate that TOP2B influences the separation between RUNX1 and two translocation partners (RUNX1T1 and EVI) in the nucleus of lymphoid cells. Specifically, we identified a TOP2B‐dependent increase in the number of nuclei displaying juxtaposed RUNX1 and RUNX1T1 loci following etoposide treatment. © 2013 Wiley Periodicals, Inc.
Severe and fatal pharmaceutical poisoning in young children in the UK

Objective Accidental poisoning in young children is common, but severe or fatal events are rare. This study was performed to identify the number of such events occurring in the UK and the medications that were most commonly responsible. Design Analysis of national data sets containing information relating to severe and fatal poisoning in children in the UK. Data sources Office of National Statistics mortality data for fatal poisoning; Paediatric Intensive Care Audit Network admissions database and the National Poisons Information Service for severe non-fatal poisoning; Hospital Episode Statistics for admission data for implicated agents. Results Between 2001 and 2013, there were 28 children aged 4 years and under with a death registered as due to accidental poisoning by a pharmaceutical product in England and Wales. Methadone was the responsible drug in 16 (57%) cases. In the UK, 201 children aged 4 years and under were admitted to paediatric intensive care with pharmaceutical poisoning between 2002 and 2012. The agent(s) responsible was identified in 115 cases, most commonly benzodiazepines (22/115, 19%) and methadone (20/115, 17%). Conclusions Methadone is the most common pharmaceutical causing fatal poisoning and a common cause of intensive care unit admissions in young children in the UK.