Miracle-dz/UniFAR-FTUs huggingface dataset:
A Structural View on the Functional Importance of the Sugar Moiety and Steroid Hydroxyls of Cardiotonic Steroids in Binding to Na,K-ATPase*

Background: Cardiotonic steroids are specific inhibitors of Na,K-ATPase important for treatment of congestive heart failure. Results: The sugar moiety and the steroid hydroxyls are pivotal for inhibition and pH dependence. Conclusion: The sugar moiety is necessary for closing the access pathway for cardiotonic steroids. Significance: Knowledge of structural and functional features of cardiotonic steroid binding could be important for drug design. The Na,K-ATPase is specifically inhibited by cardiotonic steroids (CTSs) like digoxin and is of significant therapeutic value in the treatment of congestive heart failure and arrhythmia. Recently, new interest has arisen in developing Na,K-ATPase inhibitors as anticancer agents. In the present study, we compare the potency and rate of inhibition as well as the reactivation of enzyme activity following inhibition by various cardiac glycosides and their aglycones at different pH values using shark Na,K-ATPase stabilized in the E2MgPi or in the E2BeFx conformations. The effects of the number and nature of various sugar residues as well as changes in the positions of hydroxyl groups on the β-side of the steroid core of cardiotonic steroids were investigated by comparing various cardiac glycoside compounds like ouabain, digoxin, digitoxin, and gitoxin with their aglycones. The results confirm our previous hypothesis that CTS binds primarily to the E2-P ground state through an extracellular access channel and that binding of extracellular Na+ ions to K+ binding sites relieved the CTS inhibition. This reactivation depended on the presence or absence of the sugar moiety on the CTS, and a single sugar is enough to impede reactivation. Finally, increasing the number of hydroxyl groups of the steroid was sterically unfavorable and was found to decrease the inhibitory potency and to confer high pH sensitivity, depending on their position on the steroid β-face. The results are discussed with reference to the recent crystal structures of Na,K-ATPase in the unbound and ouabain-bound states.
Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers.

PURPOSE The wild-type or variant mRNAs of several kallikrein (KLK) genes, such as KLK4, are highly expressed in ovarian carcinomas and may have potential as tumor markers. Two of these KLK genes (KLK5 and KLK7) and their proteins (hK5 and hK7) were first identified in the skin epidermis, where hK5 may be the physiological activator of hK7. The purpose of this study was to reexamine the expression of KLK5/hK5 and KLK7/hK7 and their association and to determine whether cancer-related variant transcripts were expressed. EXPERIMENTAL DESIGN The expression of KLK5/hK5 and KLK7/hK7 was analyzed in the same cohort (n = 37) of benign (n = 4) and malignant ovarian tissue (n = 23) samples and primary cultured cells (n = 21) and in 8 ovarian cancer cell lines using semiquantitative RT-PCR; Southern, Northern, and Western blot analyses; and immunohistochemistry techniques. RESULTS We showed the concordant higher expression of both KLK5/hK5 and KLK7/hK7 in ovarian carcinomas, especially late-stage serous carcinomas, compared with normal ovaries and benign adenomas. We also found that one novel KLK5 transcript with a short 5'-untranslated region and a novel KLK7 transcript with a long 3'-untranslated region were highly expressed in the ovarian cancer cell lines OVCAR-3 and PEO1, respectively, but were expressed at very low levels in normal ovarian epithelial cells. Both Western blot and immunohistochemistry analyses showed that these two enzymes are secreted from ovarian carcinoma cells. CONCLUSIONS Our study demonstrated that hK5 and hK7, or more specifically, the short KLK5 and long KLK7 transcripts, may be useful as tumor markers for epithelial-derived serous carcinomas. However, additional clinical studies assessing serum levels of these putative biomarkers are required to confirm their usefulness in the diagnosis and/or monitoring of these tumors.
Efficacy of music therapy treatment based on cycles of sessions: A randomised controlled trial

We undertook a randomised controlled trial to assess whether a music therapy (MT) scheme of administration, including three working cycles of one month spaced out by one month of no treatment, is effective to reduce behavioural disturbances in severely demented patients. Sixty persons with severe dementia (30 in the experimental and 30 in the control group) were enrolled. Baseline multidimensional assessment included demographics, Mini Mental State Examination (MMSE), Barthel Index and Neuropsychiatry Inventory (NPI) for all patients. All the patients of the experimental and control groups received standard care (educational and entertainment activities). In addition, the experimental group received three cycles of 12 active MT sessions each, three times a week. Each 30-min session included a group of three patients. Every cycle of treatment was followed by one month of wash-out. At the end of this study, MT treatment resulted to be more effective than standard care to reduce behavioural disorders. We observed a significant reduction over time in the NPI global scores in both groups (F 7,357 = 9.06, p < 0.001) and a significant difference between groups (F 1,51 = 4.84, p < 0.05) due to a higher reduction of behavioural disturbances in the experimental group at the end of the treatment (Cohen's d = 0.63). The analysis of single NPI items shows that delusions, agitation and apathy significantly improved in the experimental, but not in the control group. This study suggests the effectiveness of MT approach with working cycles in reducing behavioural disorders of severely demented patients.
Item Response Patterns on the Patient Health Questionnaire-8 in a Nationally Representative Sample of US Adults

Recent studies have shown that item responses on the Center for Epidemiologic Studies Depression Scale (CES-D) and Kessler Screening Scale for Psychological Distress (K6) exhibit the same characteristic item response patterns among the general population. However, the distributional patterns of responses on the Patient Health Questionnaire-8 (PHQ-8) among the general population have not been adequately studied. Thus, we conducted a pattern analysis of PHQ-8 item responses among US adults. Data (18,446 individuals) were obtained from the 2015 Behavioral Risk Factor Surveillance Survey (BRFSS). Item responses on the BRFSS version of the PHQ-8 were scored using the number of days response set and then converted to the original 4-point scale. The patterns of item responses were analyzed through graphical analysis. Lines of item responses scored using the number of days response set showed the same pattern among the eight items, characterized by crossing at a single point between “0 days” and “1 day,” and parallel fluctuation from “1 day” to “14 days” on a semi-logarithmic scale. Lines of item responses converted to the 4-point scale also showed the same characteristic pattern among the eight items. The present results demonstrate that the item responses on the PHQ-8 show the same characteristic patterns among items, consistent with the CES-D and the K6.
Evaluation of the Efficacy of Curcumin in the Treatment of Oral Lichen Planus: A Randomized Controlled Trial.

INTRODUCTION Oral Lichen Planus (OLP) is a chronic immunological, mucocutaneous disease with a wide range of clinical appearances. The treatment of oral lichen planus is often difficult and disappointing. AIM We have studied the efficacy of curcumin, a low molecular weight flavonoid with anti-inflammatory and anti-oxidant activities, in the treatment of OLP. MATERIALS AND METHODS In this study, a randomized, double-blind, placebo-controlled trial was conducted with a total of 20 OLP patients. The patients were randomly divided into two groups, each treated with curcumin tablets at a dose of 2000 mg/day or placebo for a period of four weeks. Furthermore, the patients of both groups received routine treatment for OLP (i.e. Mouthwash Dexamethasone 0.5 mg and suspension Nystatin 100,000 Units). The baseline data were recorded for each patient. Patients were evaluated on day 14 and after completing the course of treatment. Pain and burning sensation were measured based on the Visual Analogue Scale, and the Thongprasom Index was used for clinical improvement and healing. Mann-Whitney and independent t-test were used to compare the responses between the two groups, p-value < 0.05 was considered statistically significant. RESULTS Our analyses demonstrated no significant difference between the curcumin and placebo treated groups. CONCLUSION In conclusion, curcumin had no detectable effect in the treatment of OLP. However, a higher dose of curcumin administration and other forms of curcumin with improved bioavailability may be considered in future studies.
Nomograms for the Administration of Unfractionated Heparin in the Initial Treatment of Acute Thromboembolism – an Overview

Summary Despite the availability of low-molecular-weight heparins, unfractionated heparin (UFH) still remains the drug of choice for the initial treatment of acute venous thromboembolism in many countries. When appropriately employed, UFH treatment results in a degree of efficacy and safety that is fully comparable with that obtained with the use of heparin derivatives. The use of nomograms for the intravenous or subcutaneous administration of UFH assures that virtually all patients will promptly achieve adequate levels of anticoagulation, thus decreasing the likelihood of recurrent venous thromboembolism without extra bleeding-risk. In this article we reviewed clinical studies on the implementation and validation of UFH dosing nomograms, and attempted a quantitative analysis of their performance. According to the results of our analysis, a statistically significantly higher proportion of patients treated on the basis of a nomogram reached a therapeutic anticoagulant level within 24 h of treatment, as compared to patients treated following the standard practice (odds ratio, 3.6; 95% CI, 2.6 to 4.9). The rate of recurrent thromboembolic events was significantly lower for patients treated according to a nomogram (odds ratio, 0.3; 95% CI, 0.1 to 0.8), while no significant differences in terms of either major or minor bleedings were detected between nomogram patients and controls.
Accuracy of Visible Plaque Identification by Pediatric Clinicians During Well-Child Care

Objectives. Assess pediatric providers’ ability to identify visible plaque on children’s teeth. Methods. Pediatric providers (residents, nurse practitioners, and attendings) conducting well-child care on 15-month to 5-year-olds in an academic practice examined children’s maxillary incisors for visible plaque (recorded yes/no). A dental hygienist then examined the children and recorded the degree of visible plaque present. Results. The children’s mean age was 34 months (±15 months), and 50% had visible plaque. Providers (n = 28) identified visible plaque on 39% of children (n = 118), with 55% sensitivity and 80% specificity, and agreement with hygienist measured as a κ score was 0.34. Subgroup analyses (based on provider training level, exam experience, child age, and plaque scores) did not appreciably improve sensitivity, specificity, positive predictive value, negative predictive value, or κ scores. Conclusions. Visible plaque exams performed during well-child care may not be accurate. To comply with caries-risk assessment guidelines, providers require further education in oral exams.
Grocery purchasing among older adults by chewing ability, dietary knowledge and socio-economic status

Abstract Objectives Nutrition plays a central role in health, with poor dietary habits and nutritional intake being associated with a range of chronic diseases. The aim was to examine grocery purchasing behaviour in relation to chewing ability, dietary knowledge and socio-economic status (SES) among older adults. Design Data were collected by mailed survey in 2008. Grocery purchasing was measured using a sixteen-item index of compliance of food purchasing with dietary guidelines. Self-reported number of teeth was classified as an inadequate dentition if less than twenty-one teeth were present. Chewing ability was based on a five-item chewing index. Dietary knowledge was collected using twenty true/false items. SES was assessed using a subjective social status rating representing where people stand in society. Setting Population survey in Adelaide, South Australia. Subjects Adults aged 60–71 years. Results Responses were collected from 444 persons (response rate = 68·8 %). Among dentate persons, 24·4 % had an inadequate dentition with 10·3 % defined as ‘chewing deficient’. Multivariate regression coefficients adjusted for age, sex and income showed chewing deficiency (−5·8) and low SES (−3·6) was associated (P < 0·05) with lower grocery purchasing scores, but dietary knowledge was not statistically significant. Conclusions For older adults, chewing deficiency and lower social status were associated with lower compliance with dietary guidelines, independent of dietary knowledge.
Meiotic Arrest In Vitro by Phosphodiesterase 3-Inhibitor Enhances Maturation Capacity of Human Oocytes and Allows Subsequent Embryonic Development1

Abstract Controlling nuclear maturation during oocyte culture might improve nuclear-cytoplasmic maturation synchrony. We aimed to evaluate the quality of in vitro-matured, germinal vesicle (GV)-stage human oocytes following a prematuration culture (PMC) with a meiotic arrester, phosphodiesterase 3-inhibitor (PDE3-I). Follicles (diameter, 6–12 mm) were retrieved 34–36 h post-hCG administration from informed, consenting patients who had undergone controlled ovarian stimulation. Cumulus-enclosed oocytes (CEOs) presenting moderate expansion or full compaction were placed in PMC with the PDE3-I, Org9935, for 24 or 48 h. Subsequently, oocytes were removed from PMC, denuded of cumulus cells, matured in vitro, and fertilized, and the resulting embryos were cultured. In the presence of PDE3-I, approximately 98% of the oocytes were arrested at the GV stage. Following PDE3-I removal, oocytes acquired a higher maturation rate than oocytes that were immediately denuded of cumulus cells after retrieval and in vitro matured (67% vs. 46%, P = 0.01). In controls, immature CEOs retrieved with moderate expansion reached higher maturation rates compared to fully compacted CEOs, but in PMC groups, high values of maturation were achieved for both morphological classes of CEOs. No effect of PMC on fertilization was observed. A 24-h PMC period proved to be the most effective in preserving embryonic integrity. Similar proportions of nuclear abnormalities were observed in embryos of all in vitro groups. In summary, PMC with the specific PDE3-I had a beneficial effect on human CEOs by enhancing maturation, benefiting mainly the fully compacted CEOs. This resulted in an increased yield of mature oocytes available for insemination without compromising embryonic development. These results suggest that applying an inhibitor to control the rate of nuclear maturity by regulating intraoocyte PDE3 activity may allow the synchronization of nuclear and ooplasmic maturation.
Institutional- and Individual-Level Influences on Service Representation and Casework in Canadian Cities

Service representation—the extent to which elected officials act as ombudsmen and engage in casework to assist their constituents with problems—is a crucial aspect of contemporary democratic representation. The local level of government is a potentially fruitful location in which to explore the practice of service representation. Despite this, service representation in local governments is understudied. Using data from interviews with 52 sitting councillors and a survey of 589 sitting councillors in Canadian cities, this article explores both the commitment of councillors to service and influences on time committed to service. This research finds that service representation is an important but secondary role of Canadian councillors. Furthermore, councillors elected in wards commit more time to service than councillors elected at-large, and councillors with strong service role perceptions also commit more time to service.
Unexpected Presence of Graminan- and Levan-Type Fructans in the Evergreen Frost-Hardy Eudicot Pachysandra terminalis (Buxaceae): Purification, Cloning, and Functional Analysis of a 6-SST/6-SFT Enzyme1[W]

About 15% of flowering plants accumulate fructans. Inulin-type fructans with β(2,1) fructosyl linkages typically accumulate in the core eudicot families (e.g. Asteraceae), while levan-type fructans with β(2,6) linkages and branched, graminan-type fructans with mixed linkages predominate in monocot families. Here, we describe the unexpected finding that graminan- and levan-type fructans, as typically occurring in wheat (Triticum aestivum) and barley (Hordeum vulgare), also accumulate in Pachysandra terminalis, an evergreen, frost-hardy basal eudicot species. Part of the complex graminan- and levan-type fructans as accumulating in vivo can be produced in vitro by a sucrose:fructan 6-fructosyltransferase (6-SFT) enzyme with inherent sucrose:sucrose 1-fructosyltransferase (1-SST) and fructan 6-exohydrolase side activities. This enzyme produces a series of cereal-like graminan- and levan-type fructans from sucrose as a single substrate. The 6-SST/6-SFT enzyme was fully purified by classic column chromatography. In-gel trypsin digestion led to reverse transcription-polymerase chain reaction-based cDNA cloning. The functionality of the 6-SST/6-SFT cDNA was demonstrated after heterologous expression in Pichia pastoris. Both the recombinant and native enzymes showed rather similar substrate specificity characteristics, including peculiar temperature-dependent inherent 1-SST and fructan 6-exohydrolase side activities. The finding that cereal-type fructans accumulate in a basal eudicot species further confirms the polyphyletic origin of fructan biosynthesis in nature. Our data suggest that the fructan syndrome in P. terminalis can be considered as a recent evolutionary event. Putative connections between abiotic stress and fructans are discussed.
Hymenobacter koreensis sp. nov. and Hymenobacter saemangeumensis sp. nov., isolated from estuarine water.

Two Gram-reaction-negative, rod-shaped, non-motile and red-pink-pigmented bacterial strains, designated GYR3077(T) and GSR0100(T), were isolated from a water sample of the Mangyung estuary enclosed by the Saemangeum Embankment in JEOLlabuk-do, South Korea, and were characterized using a polyphasic approach. 16S rRNA genes of strains GYR3077(T) and GSR0100(T) exhibited sequence similarities of 95.9 % to Hymenobacter deserti ZLB-3(T) and 96.6 % to Hymenobacter soli PB17(T), respectively, and indicated that these isolates belonged to the phylum Bacteroidetes. The major cellular fatty acids present in the two isolates were iso-C15 : 0, C16 : 1ω5c, summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B) and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The major respiratory quinone and polyamine patterns were menaquinone-7 and sym-homospermidine, characteristic of the genus Hymenobacter. Flexirubin-type pigments were absent in both strains. The DNA G+C contents of strains GYR3077(T) and GSR0100(T) were 60.2 mol% and 61.9 mol%, respectively. The major polar lipid of strains GYR3077(T) and GSR0100(T) was phosphatidylethanolamine. Based on the morphological and physiological properties, strains GYR3077(T) and GSR0100(T) were considered to represent two novel species of the genus Hymenobacter, for which the names Hymenobacter koreensis sp. nov. (type strain GYR3077(T) = KACC 16451(T) = JCM 17924(T)) and Hymenobacter saemangeumensis sp. nov. (type strain GSR0100(T) = KACC 16452(T) = JCM 17923(T)) are proposed.
Diacetylbis(N(4)-methylthiosemicarbazonato) Copper(II) (CuII(atsm)) Protects against Peroxynitrite-induced Nitrosative Damage and Prolongs Survival in Amyotrophic Lateral Sclerosis Mouse Model*

Background: CuII(atsm) [(diacetylbis(N(4)-methylthiosemicarbazonato) copper(II)] was orally administrated to transgenic SOD1G93A mice. Results: Treatment significantly prolonged lifespan with preservation of motor neurons. Reduced protein oxidation, attenuated astrocyte, and microglial activation also resulted from treatment. Conclusion: CuII(atsm) is neuroprotective in this model even when treatment begins after the onset of disease symptoms. Significance: The drug has therapeutic potential for amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis (ALS) is a progressive paralyzing disease characterized by tissue oxidative damage and motor neuron degeneration. This study investigated the in vivo effect of diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)), which is an orally bioavailable, blood-brain barrier-permeable complex. In vitro the compound inhibits the action of peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) and subsequent nitration of cellular proteins. Oral treatment of transgenic SOD1G93A mice with CuII(atsm) at presymptomatic and symptomatic ages was performed. The mice were examined for improvement in lifespan and motor function, as well as histological and biochemical changes to key disease markers. Systemic treatment of SOD1G93A mice significantly delayed onset of paralysis and prolonged lifespan, even when administered to symptomatic animals. Consistent with the properties of this compound, treated mice had reduced protein nitration and carbonylation, as well as increased antioxidant activity in spinal cord. Treatment also significantly preserved motor neurons and attenuated astrocyte and microglial activation in mice. Furthermore, CuII(atsm) prevented the accumulation of abnormally phosphorylated and fragmented TAR DNA-binding protein-43 (TDP-43) in spinal cord, a protein pivotal to the development of ALS. CuII(atsm) therefore represents a potential new class of neuroprotective agents targeting multiple major disease pathways of motor neurons with therapeutic potential for ALS.
Cell-Mediated Immune Responses to Smallpox Vaccination

ABSTRACT We report that vaccine dilution (1:1 or 1:10) and previous vaccinia virus vaccination status had no significant effect on cell-mediated immune responses (i.e., the immediate vaccinia virus-specific gamma interferon-producing T-cell response measured by enzyme-linked immunospot assay) 1 month after smallpox vaccination (Lancy-Vaxina; Berna Biotech, Switzerland).
STAT RAD: A Potential Real-Time Radiation Therapy Workflow

The American Cancer Society estimates that approximately 1.5 million people in the United States will be diagnosed with cancer, and 560,000 will die of cancer in 2010 (Jemal et al., 2010). These numbers are projected to increase rapidly in the near future due to national demographics with a large number of Americans reaching retirement age over the next 15-20 years, resulting in a doubling of projected new cancer diagnoses in 2050 to 3 million (Hayat et al., 2007). Most cancer deaths involve extensive locoregional tumors or metastatic disease to brain, lung, liver, or bone causing pain, disability, and decreased quality of life. As treatments for cancer improve, patients are living longer with advanced cancer than ever before, and the management of metastatic disease is becoming increasingly more multi-disciplinary and complex with patients treated simultaneously with systemic therapy, surgery, and radiation. It is well documented that cancer-related pain is often inadequately controlled in the palliative care setting, and both the pain and opioid medication interfere with patient function and quality of life (Bruera & Kim, 2003; Cleeland et al., 1994; McGuire, 2004). Radiotherapy is an important treatment for the alleviation of pain and suffering for cancer patients. It prevents pathologic bone fractures, and palliates tumor-induced obstruction, bleeding, and pain that is not well palliated with pharmacologic treatment (Halperin et al., 2008).