Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging role of Radium-223 in the growing therapeutic armamentarium of metastatic castration-resistant prostate cancer

ABSTRACT Introduction: During the last few years, the therapeutic armamentarium of castration resistant prostate cancer (mCRPC) has been enriched with the introduction of new effective therapies with proved survival benefit and quality of life gain, including cabazitaxel, abiraterone, enzalutamide, and Radium-223. Areas covered: Bone metastases represent a substantial cause of morbidity in mCRPC with a high rate of related skeletal events (SREs). In case of multifocal pain due to diffuse osteoblastic metastases, treatment with bone-targeting radiopharmaceutical agents can provide palliation from pain. Radium-223, a calcium-mimetic, is the first α-particle emitting radiopharmaceutical that prolonged overall survival, delayed symptomatic skeletal events and improved quality of life in mCRPC. Expert opinion: In this therapeutic scenario, no clear evidences support the best way to sequence these available agents and there is an urgent need for prospective studies to define it. 223Ra is a firmly established therapeutic option in CRPC with symptomatic bone metastases and no visceral/bulky nodal involvement, with an undeniable advantage over new hormonal agents, given its peculiar mechanism of action. Current ongoing randomized clinical trials will clarify the optimal use of this effective therapy in the therapeutic armamentarium of CRPC either alone or combined with other new approved agents and whether there is a role in patients with asymptomatic disease.
Vasculitis and anti-thyroid medication.

We appreciate the opportunity to respond to the comments made by Woywodt et al., regarding our evaluation of the association of thyroid disease and vasculitis [1]. Their major concern is that our study does not support our statement that the use of anti-thyroid agents does not account for many cases of ANCA-Small Vessel Vasculitis (ANCA-SVV) in the general population, a contention we continue to support.
Frame-of-reference training and cognitive categorization: an empirical investigation of rater memory issues.

We considered the effects of frame-of-reference (FOR) training on raters' ability to correctly classify ratee performance as well as their ability to recognize previously observed behaviors. The purpose was to examine the cognitive changes associated with FOR training to better understand why such training generally improves rating accuracy. We trained college students (N = 94) using either FOR or control procedures, had them observe three managers on videotape, and rate the managers on three performance dimensions. Results supported our hypotheses that, compared with control training, FOR training led to better rating accuracy and better classification accuracy. Also consistent with predictions, FOR training resulted in lower decision criteria (i.e., higher bias) and lower behavioral accuracy on a recognition memory task involving impression-consistent behaviors. The implications of these results are discussed, particularly in terms of the ability of FOR-trained raters to provide accurate performance feedback to ratees.
A database of vertebrate longevity records and their relation to other life‐history traits

Longevity is a major characteristic of animals that has long fascinated scientists. In this work, we present a comprehensive database of animal longevity records and related life‐history traits entitled AnAge, which we compiled and manually curated from an extensive literature. AnAge started as a collection of longevity records, but has since been expanded to include quantitative data for numerous other life‐history traits, including body masses at different developmental stages, reproductive data such as age at sexual maturity and measurements of reproductive output, and physiological traits related to metabolism. AnAge features over 4000 vertebrate species and is a central resource for applying the comparative method to studies of longevity and life‐history evolution across the tree of life. Moreover, by providing a reference value for longevity and other life‐history traits, AnAge can prove valuable to a broad range of biologists working in evolutionary biology, ecology, zoology, physiology and conservation biology. AnAge is freely available online (http://genomics.senescence.info/species/).
Determinants of FDI and its Impact on BRICS Countries: A Panel Data Approach

Abstract This paper examines the impact of factors determining Foreign Direct Investment (FDI) inflows of BRICS countries using annual dataset from the period 1994–2014. The paper proposes to compare the overall trends and factors impact on the FDI in the BRICS countries. The study employs Panel Data analysis and examines the selected variables like Index of Industrial Production (IIP), Gross Domestic Product (GDP), Foreign Exchange Rate (FOREX), Stock Market Capitalization, Infrastructure Index, and Stock Market Turnover ratio. The empirical results are robust in general for alternative variables determining FDI flows. The policy implication of this study is that increasing interest of economic integration around the globe and interdependence of FDI between member's countries is an important feature for maintaining sustainability of growth.
Activation of Toll-Like Receptor 2 on Human Dendritic Cells Triggers Induction of IL-12, But Not IL-101

Mammalian Toll-like receptors (TLRs) are required for cell activation by bacterial lipoproteins (bLP) and LPS. Stimulation of monocytes with bLP and LPS results in a TLR-dependent induction of immunomodulatory genes leading to the production of pro-inflammatory cytokines. In this paper, we compared the expression and response of TLRs on monocytes and dendritic cells (DC). TLR2, but not TLR4, was detected on peripheral blood monocytes and DC, in lymphoid tissue CD1a+ DC as well as on in vitro monocyte-derived DC. Upon stimulation with bLP or LPS, monocytes produced IL-12 and IL-10 at similar levels, whereas monocyte-derived DC produced comparable levels of IL-12, but little IL-10. Greater than 90% of the bLP-induced production of IL-12 was blocked by anti-TLR2 mAb. Thus, DC express TLR2 and activation of this receptor by bLP provides an innate mechanism by which microbial pathogens preferentially activate cell-mediated immunity.
Analysis of p53/BAX/p16(ink4a/CDKN2) in esophageal squamous cell carcinoma: high BAX and p16(ink4a/CDKN2) identifies patients with good prognosis.

PURPOSE We have previously shown that loss of BAX expression is a negative prognostic factor in metastatic colorectal cancer. In the present study, we addressed the prognostic relevance of BAX and its upstream regulator p53 in squamous cell carcinoma (SCC) of the esophagus. Analysis of p16(ink4a/CDKN2) was included because p16(ink4a/CDKN2) and p53 were shown previously to cooperate during induction of cell cycle arrest and apoptosis. PATIENTS AND METHODS Retrospective analysis of 53 patients with curative intended R0 resection of esophageal SCC was done. Protein expression of BAX, p53, and p16(ink4a/CDKN2) was investigated by immunohistochemistry. In addition, tumor DNA was screened for BAX frameshift mutations by fragment length analysis and for p53 mutations by single-strand conformation polymorphism-polymerase chain reaction. RESULTS Overall median survival was 13.7 months. Patients with high BAX protein expression had a median survival of 19.5 months versus 8.0 months with low BAX expression (P <.005). High p16(ink4a/CDKN2) protein expression was associated with a median survival of 23.8 months versus 9.7 months with low p16(ink4a/CDKN2) (P =.011). The best survival (median, 45.8 months) was seen in a subgroup of 12 patients whose tumors bore the combination of both favorite phenotypes (ie, high BAX and high p16(ink4a/CDKN2) protein expression). CONCLUSION In this retrospective investigation, the combined analysis of BAX and p16(ink4a/CDKN2) shows subgroups in SCC of the esophagus with favorable (p16(ink4a/CDKN2)/BAX high expressing) or poor prognosis (loss of p16(ink4a/CDKN2)/loss of BAX). We suggest that such a multimarker analysis of apoptosis pathways could be useful for individualization of therapeutic strategies in the future, and suggest prospective studies to confirm these results.
Biocompatible Azide–Alkyne “Click” Reactions for Surface Decoration of Glyco‐Engineered Cells

Bio‐orthogonal copper (I)‐catalyzed azide–alkyne cycloaddition (CuAAC) has been widely used to modify azide‐ or alkyne‐bearing monosaccharides on metabolic glyco‐engineered mammalian cells. Here, we present a systematic study to elucidate the design space for the cytotoxic effects of the copper catalyst on NIH 3T3 fibroblasts and on HEK 293‐F cells. Monitoring membrane integrity by flow cytometry and RT‐PCR analysis with apoptotic and anti‐apoptotic markers elucidated the general feasibility of CuAAC, with exposure time of the CuAAC reaction mixture having the major influence on biocompatibility. A high labeling efficiency of HEK 293‐F cells with a fluorescent alkyne dye was rapidly achieved by CuAAC in comparison to copper free strain‐promoted azide–alkyne cycloaddition (SPAAC). The study details effective and biocompatible conditions for CuAAC‐based modification of glyco‐engineered cells in comparison to its copper free alternative.
Gastrointestinal motor-stimulating activity of macrolide antibiotics and analysis of their side effects on the canine gut

For clarification of the nature of the side effects of macrolide antibiotics on the gastrointestinal tract, the motor-stimulating activity of these agents was studied in unanesthetized dogs. The results showed that erythromycin and oleandomycin, the 14-membered macrolides with two side chain sugars combined at C3 and C5 in a glycosidic linkage in parallel, strongly stimulate gastrointestinal motor activity, an action accompanied by vomiting at large doses. On the other hand, leucomycin, acetylspiramycin, and tylosin, belonging to a 16-membered macrolide with two side chain sugars in series combined at C5 of the lactone ring, did not induce contractions of the gastrointestinal tract. Motor-stimulating activity by erythromycin and oleandomycin was greatly inhibited by atropine sulfate. These results point to structure-physiological activity relationships.
Magnetic resonance brain imaging in patients with visual vertigo

Patients with visual vertigo (VV) report dizziness provoked by moving visual surroundings. It has been suggested that these subjects develop a compensation strategy for a vestibulo‐proprioceptive deficit and rely excessively on visual input. We have postulated that patients with VV might have brain abnormalities that interfere with appropriate processing of visual stimulation and performed a brain MRI study to verify this hypothesis.
Revisiting Nurse Turnover Costs: Adjusting for Inflation

Organizational knowledge of nurse turnover costs is important, but gathering these data frequently may not always be feasible in today's fast-paced and complex healthcare environment. The author presents a method to inflation adjust baseline nurse turnover costs using the Consumer Price Index. This approach allows nurse executives to gain current knowledge of organizational nurse turnover costs when primary data collection is not practical and to determine costs and potential savings if nurse retention investments are made.
Disorders of sex development among Sudanese children: 5-year experience of a pediatric endocrinology clinic

Abstract Background: The birth of a child with disorders of sex development (DSDs) is considered a medical and psychosocial emergency. Management of these cases requires facilities and a multidisciplinary team. In developing countries, this is made difficult by the lack of facilities in addition to sociocultural and religious factors that can affect management. This is the first experience to be published from Sudan. Objective: The aim of this study was to see the prevalence, etiological factors, management, and problems faced in handling these cases. Methods: This is a retrospective descriptive study reviewing the records of all cases referred to a pediatric endocrinology clinic over a 5-year period. Cases were managed by a multidisciplinary team. Results: One hundred fifty-six cases were seen, of which 122 were included in the study. A total of 79 (64.8%) were born at home, whereas 59 (52.2%) of the cases were not observed at birth by health-care providers. The average cost of investigating a case was $250–300. The investigations showed that 69 had XX DSD and 45 had XY DSD. The most common cause of XX DSD was congenital adrenal hyperplasia and that of XY DSD was androgen insensitivity syndrome. Twenty-three (19%) needed sex reassignment. There was a preference for the male sex. Conclusion: DSDs are not uncommon in Sudan. Because of lack of awareness and sociocultural reasons cases are referred late. Investigating these cases is expensive and has to be supported, and more multidisciplinary teams have to be trained to make services accessible and affordable.
Growth differentiation factor 9 reverses activin A suppression of steroidogenic acute regulatory protein expression and progesterone production in human granulosa-lutein cells.

BACKGROUND We have reported that growth differentiation factor 9 (GDF9) can enhance activin A (β(A)β(A))-induced inhibin B (αβ(B)) secretion in human granulosa-lutein (hGL) cells, but its effects on steroidogenic acute regulatory protein (StAR), ovarian steroidogenic enzymes, and progesterone production are unknown. We undertook this study to further evaluate GDF9 in this regard. METHODS hGL cells from women undergoing in vitro fertilization treatment were cultured with and without small interfering RNA (siRNA) transfection targeted at inhibin α-subunit or GDF9 before treatment with GDF9, activin A, FSH, or combinations. We compared StAR, P450 side-chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase expression in hGL cells and progesterone levels in culture media after these treatments. mRNA, protein, and hormone levels were assessed with real-time RT-PCR, immunoblotting, and ELISA, respectively. Data were analyzed by ANOVA followed by Tukey's test. RESULTS Activin A alone reduced basal and FSH-induced progesterone production by decreasing the expression of StAR protein, which regulates the rate-limiting step in steroidogenesis but not P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase. GDF9 attenuated these activin A effects on StAR and progesterone. After transfection of α-subunit siRNA, activin A level increased (P < 0.001), whereas basal and activin A-induced inhibin B levels (with and without GDF9) decreased. Furthermore, the effects of GDF9 in reversing activin A suppression of progesterone production were attenuated (P < 0.001). Transfection of GDF9 siRNA decreased GDF9 as expected and led to lower StAR expression and progesterone secretion than those observed with activin A treatment alone. CONCLUSION GDF9 attenuates the suppressive effects of activin A on StAR expression and progesterone production by increasing the expression of inhibin B, which acts as an activin A competitor.
Pilot Evaluation of Parent–Child Interaction Therapy Delivered in an Australian Community Early Childhood Clinic Setting

Objective: Parent–child interaction therapy (PCIT) is a short-term, evidence-based parent training intervention used widely in the treatment of behaviourally disordered preschool-aged children. Outcome studies have shown PCIT to be associated with lasting improvements in child and sibling behaviours and in the interactional styles, stress levels, confidence, and psychological functioning of parents. To date, however, all outcome studies have been conducted in university research clinic settings, and therefore understanding about the effectiveness of PCIT applied in a real-world setting has been limited. The present study evaluated the effectiveness of PCIT delivered to families in an Australian community-based early childhood clinic. Method: Participants included 43 families with children aged 19–52 months who were referred for treatment of disruptive child behaviours and who completed PCIT treatment at the Karitane Toddler Clinic, in Sydney, Australia. Parents provided pre- and post-treatment ratings of child behaviours, parental stress, parental psychopathology and parental attitudes to therapy. Results: At the end of the programme, clinically and statistically significant improvements were seen in child behaviours and parental well-being, and parents reported high levels of satisfaction with treatment. Conclusions: Implications for the implementation of PCIT programmes in community-based settings are discussed and areas of further research are identified.
The Intonation Of English Statements And Questions A Compositional Interpretation

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Associations of serum C-reactive protein with physical activity, fitness and fatness in South African adolescents

Globally the prevalence of overweight is increasing significantly, not only in economically developed regions, but also in developing countries. In South Africa, the prevalence of combined overweight and obesity among high-school children increased from 21.2% in 20021 to 25% in 2008,2 with 35% of high-school girls being overweight or obese.2
Political Connection,Marketization Process and the Cost of Equity Capital——Empirical Evidence from Chinese Private Listed Companies

Choosing Chinese private listed enterprises as samples,this paper studies the impact of political connections on the cost of equity capital,the results show that:in the region of lower degree of marketization,the operating performance of firms is uncertainty because of government's interventions,PCFs(political - connected firms ) bear the higher costs of equity capital;in the region of higher degree of marketization,because of government's interventions are less,political connection represents an honor for firms or a good relationship with government,so PCFs have the lower costs of equity capital.PCFs must bear the higher costs of equity capital when listed firms transfer interests to controlling shareholders, because minority shareholders know that they can't share the benefits of political connection.This study provides a meaningful perspective for clarifying the pros and cons of political connection for firms and investors.
When Smart Devices Interact With Pervasive Screens

The meeting of pervasive screens and smart devices has witnessed the birth of screen-smart device interaction (SSI), a key enabler to many novel interactive use cases. Most current surveys focus on direct human-screen interaction, and to the best of our knowledge, none have studied state-of-the-art SSI. This survey identifies three core elements of SSI and delivers a timely discussion on SSI oriented around the screen, the smart device, and the interaction modality. Two evaluation metrics (i.e., interaction latency and accuracy) have been adopted and refined to match the evaluation criterion of SSI. The bottlenecks that hinder the further advancement of the current SSI in connection with this metrics are studied. Last, future research challenges and opportunities are highlighted in the hope of inspiring continuous research efforts to realize the next generation of SSI.
Internal medicine house officers’ attitudes and experience with patients who overstep patient–physician boundaries

Maintenance of appropriate social boundaries is an essential aspect of patient care. Given limited clinical experience, house officers may be especially vulnerable to such transgressions. We studied the frequency of patients’ transgressions of boundaries and house officer responses to these transgressions. An online survey was administered to internal medicine house officers at the University of Michigan Health System that addressed the frequency of patient–physician boundary transgressions, house officer responses to transgressions, and the perceived need for education regarding transgressions. The frequency of reported patient transgressions of various boundaries during the past 6 months ranged from 0 to more than 30. The most common reported incident was being called by their first name, and the least common incidents included patients engaging/attempting to engage in sexual contact and attempting to give expensive gifts. Most respondents denied the need for education regarding appropriate boundaries with patients; however, most perceived a need for training on how to respond to transgressions. Overall, there was a wide range in reported frequencies of transgressions. The frequency of transgressions reported by house officers was greater than what is previously described for attending physicians though their responses to transgressions were similar.
Rare congenital absence of tail (anury) and anus (atresia ani) in male camel (Camelus dromedarius) calf

A one-day old male camel calf was presented to the Al-Qattara Veterinary Hospital with complaints of abdominal straining and lack of defecation. On examination it was found that the calf had no tail, the posterior sacral margin was blunt and the anal opening was absent. The case was diagnosed as congenital anury with atresia ani. The animal was sedated with 0.1 mg/kg of xylazine administered intramuscularly and under local infiltration with 2% lidocaine a circular incision was made at the anal area to create an anal opening. The animal passed plenty of meconium. The cut edges were sutured with horizontal mattress sutures. The animal was administered penicillin and streptomycin for 5 days and had an uneventful recovery. It is reported that congenital anury rarely occurs in one humped camel and accompanied atresia ani can be surgically treated.
Comparative Study on Signal Transduction in Endothelial Cells After Anti-A/B and Human Leukocyte Antigen Antibody Reaction: Implication of Accommodation

Background. Recent development of immunosuppressive therapy has provided a platform for clinical human leukocyte antigen (HLA)- and ABO-incompatible kidney transplantation. However, the prognosis seems to be different between the two. Accommodation, the condition of no injury even in the presence of antidonor antibody, is one of the key factors for successful transplantation with antidonor antibody. The purpose of this study was to compare signal transduction between anti-A/B and anti-HLA antibody reaction and to elucidate the mechanisms underlying accommodation. Methods. Blood type A- or B-transferase gene was transfected into human EA.hy926 endothelial cells. After cell sorting, A- or B-expressing cells at high levels were obtained. The effects of anti-HLA and anti-A/B antibody binding on complement-mediated cytotoxicity and signal transduction were examined. Results. Preincubation with anti-HLA antibodies only at low levels (<10% of saturation level) or anti-A/B antibodies at high levels (even at near saturation levels) for 24 hr resulted in resistance to complement-mediated cytotoxicity. Anti-A/B antibody ligation inactivated ERK1/2 pathway and increased complement regulatory proteins such as CD55 and CD59, whereas anti-HLA ligation activated PI3K/AKT pathway and increased cytoprotective genes such as hemeoxygenase-1 and ferritin H. Conclusion. Complement inhibition by upregulation of CD55 and CD59 through ERK1/2 inactivation might play a substantial role in accommodation after ABO-incompatible transplantation, which could also explain the intriguing finding of C4d deposition in the graft without rejection.