Miracle-dz/UniFAR-FTUs huggingface dataset:
Second-line hormonal therapy for advanced prostate cancer: a shifting paradigm.

PURPOSE To discuss the evolution of new concepts in the Use of second-line hormonal therapy for patients with progressive prostate cancer despite androgen deprivation. DESIGN Pertinent contemporary prostate-specific antigen (PSA)-based reports of the utility of secondary hormonal maneuvers after treatment with combined androgen blockade (CAB) were reviewed. RESULTS The use of PSA as an end point in hormonerefractory prostate cancer (HRPC) trials is more widely accepted, but still remains somewhat controversial. Using PSA as an end point, it is clear that a variety of secondary hormonal maneuvers can result in responses. Antiandrogen withdrawal is efficacious in approximately 20% of patients and can be observed with a variety of antiandrogens, including flutamide, bicalutamide, and megestrol acetate. A variety of regimens, including megestrol, bicalutamide, glucocorticoids, aminoglutethimide, and ketoconazole, retain activity (14% to 75% PSA response proportion) even in patients who have failed to respond to CAB and flutamide withdrawal. CONCLUSION Once CAB (suppression of gonadal and adrenal androgen) is undertaken, further hormonal maneuvers remain efficacious in some patients with progressive prostate cancer. Antiandrogen withdrawal is now a mandatory maneuver before proceeding to other regimens. It is clear that certain patients will continue to respond to hormonal maneuvers even after antiandrogen withdrawal. An understanding of the molecular basis of these responses may result in the development of a more targeted therapy in the future.
Conditional Tail-Risk in Cryptocurrency Markets

Abstract In this paper we use C o V a R to estimate the conditional tail-risk in the markets for bitcoin, ether, ripple and litecoin and find that these cryptocurrencies are highly exposed to tail-risk within cryptomarkets, while they are not exposed to tail-risk with respect to other global assets, like the U.S. equity market or gold. Although cryptocurrency returns are highly correlated one with the other, we find that idiosyncratic risk can be significantly reduced and that portfolios of cryptocurrencies offer better risk-adjusted and conditional returns than individual cryptocurrencies. These results indicate that portfolios of cryptocurrencies could offer attractive returns and hedging properties when included in investors’ portfolios. However, when we account for liquidity, the share of crypto assets in investors’ optimal portfolio is small.
Carer distress in the general population: results from the Sydney Older Persons Study.

OBJECTIVE To assess distress in a sample of carers who were selected from a community survey rather than recruited via community-service agencies. METHODS A community survey was carried out on 630 people aged 75 or over living in Sydney, Australia. Informants nominated by these elderly people were divided into full carer (n = 21), partial carer (n = 187) and non-carer groups (n = 344). Informants completed the General Health Questionnaire (a continuous measure of psychiatric symptoms), the life satisfaction index (a measure of well-being) and the interpersonal bonding measure (a measure of quality of the relationship with the elderly person). Elderly participants had a medical examination, were assessed for disability and were questioned about use of services. RESULTS Elderly people who had a full carer were more disabled and had more medical diagnoses. Full, but not partial, carers reported more psychiatric symptoms and lower life satisfaction. In multivariate analysis, the main determinant of carer distress was a relationship in which the carer felt controlled by the elderly person. CONCLUSION When carers are selected from a population-based sample, only those who are full carers are more distressed. However, relationship factors are the most important determinant of distress.
Binding of Elongation Factor eEF1A2 to Phosphatidylinositol 4-Kinase β Stimulates Lipid Kinase Activity and Phosphatidylinositol 4-Phosphate Generation*

Eukaryotic protein translation elongation factor 1 α 2 (eEF1A2) is an oncogene that transforms mammalian cell lines and increases their tumorigenicity in nude mice. Increased expression of eEF1A2 occurs during the development of breast, ovarian, and lung cancer. Here, we report that eEF1A2 directly binds to and activates phosphatidylinositol 4-kinase III β (PI4KIIIβ), an enzyme that converts phosphatidylinositol to phosphatidylinositol 4-phosphate. Purified recombinant eEF1A2 increases PI4KIIIβ lipid kinase activity in vitro, and expression of eEF1A2 in rat and human cells is sufficient to increase overall cellular phosphatidylinositol 4-kinase activity and intracellular phosphatidylinositol 4-phosphate abundance. siRNA-mediated reduction in eEF1A2 expression concomitantly reduces phosphatidylinositol 4-kinase activity. This identifies a physical and functional relationship between eEF1A2 and PI4KIIIβ.
A novel percutaneous system for bone graft delivery and containment for elevation and stabilization of vertebral compression fractures. Technical note.

OBJECT Vertebroplasty and kyphoplasty are minimally invasive procedures used to treat persistently symptomatic vertebral compression fractures (VCFs). Both interventions usually involve injection of polymethyl methacrylate (PMMA). The purpose of this technical note was to review the theory and surgical technique for a novel percutaneous system for fracture reduction and stabilization of VCFs by using bone graft. METHODS This technical note highlights the Optimesh system as an alternative method of minimally invasive VCF reduction and stabilization with the delivery of a bone graft containment device. Instead of using PMMA as in vertebroplasty or kyphoplasty, this system allows the delivery of allograft and/or autograft bone, with its osteoinductive, osteoconductive, and osteogenic properties. CONCLUSIONS This system allows for restoration of sagittal alignment of the spine with direct control of bone graft delivery by using a mesh graft containment device that allows for ingrowth of new bone and vascular tissue.
Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women.

BACKGROUND Mammographic density and circulating sex hormones are two well-confirmed predictors of breast cancer risk. Whether mammographic density reflects levels of endogenous sex hormones is unclear. We examined whether these predictors are independently associated with breast cancer risk in a prospective study. METHODS We conducted a nested case-control study within the Nurses' Health Study cohort of 253 case subjects with breast cancer and 520 control subjects. All participants were postmenopausal women who were not using postmenopausal hormones at the time of both blood collection and mammography. Plasma levels of estradiol, free estradiol, testosterone, and free testosterone were evaluated. Mammographic density was assessed by use of computer-assisted analysis of mammograms. Logistic regression models that were adjusted for matching variables and potential confounders were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS Levels of circulating sex steroids and mammographic density were both statistically significantly and independently associated with breast cancer risk. The relative risk of breast cancer associated with mammographic density (RR for highest quartile compared with lowest quartile = 3.8, 95% CI = 2.2 to 6.6; P(trend)<. 001) changed little when the analysis was adjusted for circulating estradiol (RR = 3.9, 95% CI = 2.2 to 6.9; P(trend)<. 001) or circulating testosterone (RR = 4.1, 95% CI = 2.3 to 7.2; P(trend)<. 001). Circulating levels of estradiol (RR = 2.4, 95% CI = 1.4 to 4.0) and of testosterone (RR = 2.0, 95% CI = 1.2 to 3.1) were both associated with breast cancer risk, before and after adjustment for mammographic density. In a joint analysis of mammographic density and plasma testosterone, the risk of breast cancer was highest in the highest tertiles of both relative to the lowest tertiles of both (RR = 6.0, 95% CI = 2.6 to 14.0). A similar pattern was observed in the joint analysis of estradiol and mammographic density (RR = 4.1, 95% CI = 1.7 to 9.8). CONCLUSIONS Circulating sex steroid levels and mammographic density appear strongly and independently associated with the risk of breast cancer in postmenopausal women.
Performance of a whole-body PET scanner using curve-plate NaI(Tl) detectors.

UNLABELLED A whole-body PET scanner, without interplane septa, has been designed to achieve high performance in clinical applications. The C-PET scanner, an advancement of the PENN PET scanners, is unique in the use of 6 curved NaI(Tl) detectors (2.54 cm thick). The scanner has a ring diameter of 90 cm, a patient port diameter of 56 cm, and an axial field of view of 25.6 cm. A (137)Cs point source is used for transmission scans. METHODS Following the protocols of the International Electrotechnical Commission ([IEC] 61675-1) and the National Electrical Manufacturers Association ([NEMA] NU-2-1994 and an updated version, NU2-2001), point and line sources, as well as uniform cylinders, were used to determine the performance characteristics of the C-PET scanner. An image-quality phantom and patient data were used to evaluate image quality under clinical scanning conditions. Data were rebinned with Fourier rebinning into 2-dimensional (slice-oriented) datasets and reconstructed with an iterative reconstruction algorithm. RESULTS The spatial resolution for a point source in the transaxial direction was 4.6 mm (full width at half maximum) at the center, and the axial resolution was 5.7 mm. For the NU2-1994 analysis, the sensitivity was 12.7 cps/Bq/mL (444 kcps/microCi/mL), the scatter fraction was 25%, and the peak noise equivalent count rate (NEC) for a uniform cylinder (diameter = 20 cm, length = 19 cm) was 49 kcps at an activity concentration of 11.2 kBq/mL. For the IEC protocol, the peak NEC was 41 kcps at 12.3 kBq/mL, and for the NU2-2001 protocol, the peak NEC was 14 kcps at 3.8 kBq/mL. The NU2-2001 NEC value differed significantly because of differences in the data analysis and the use of a 70-cm-long phantom. CONCLUSION Compared with previous PENN PET scanners, the C-PET, with its curved detectors and improvements in pulse shaping, integration dead time, and triggering, has an improved count-rate capability and spatial resolution. With the refinements in the singles transmission technique and iterative reconstruction, image quality is improved and scan time is shortened. With single-event transmission scans interleaved between sequential emission scans, a whole-body study can be completed in <1 h. Overall, C-PET is a cost-effective PET scanner that performs well in a broad variety of clinical applications.
Cerebral, facial, and orbital involvement in Erdheim-Chester disease: CT and MR imaging findings.

PURPOSE To retrospectively review the brain magnetic resonance (MR) imaging and computed tomographic (CT) findings in patients with Erdheim-Chester disease (ECD). MATERIALS AND METHODS The ethics committee required neither institutional review board approval nor informed patient consent for retrospective analyses of the patients' medical records and imaging data. The patients' medical files were retrospectively reviewed in accordance with human subject research protocols. Three neuroradiologists in consensus analyzed the signal intensity, location, size, number, and gadolinium uptake of lesions detected on brain MR images obtained in 33 patients with biopsy-proved ECD. RESULTS Thirty patients had intracranial, facial bone, and/or orbital involvement, and three had normal neurologic imaging findings. The hypothalamic-pituitary axis was involved in 16 (53%) of the 30 patients, with six (20%) cases of micronodular or nodular masses of the infundibular stalk. Meningeal lesions were observed in seven (23%) patients. Three (10%) patients had bilateral symmetric T2 high signal intensity in the dentate nucleus areas, and five (17%) had multiple intraaxial enhancing masses. Striking intracranial periarterial infiltration was observed in three (10%) patients. Another patient (3%) had a lesion in the lumen of the superior sagittal sinus. Nine (30%) patients had orbital involvement. Twenty-four (80%) patients had osteosclerosis of the facial and/or skull bones. At least two anatomic sites were involved in two-thirds (n = 20) of the patients. Osteosclerosis of the facial bones associated with orbital masses and either meningeal or infundibular stalk masses was seen in eight (27%) patients. CONCLUSION Lesions of the brain, meninges, facial bones, and orbits are frequently observed and should be systematically sought on the brain MR and CT images obtained in patients with ECD, even if these patients are asymptomatic. Careful attention should be directed to the periarterial environment.
Role of reciprocity and innovativeness on performance in a developing context: Empirical evidence from Africa

Generally, investors tend to invest when likelihood of success is high. Many investors consider Africa as one market and neglect individual differences among African countries. Africa is mostly considered a high-risk market and conceptually innovativeness involves uncertainty, which precedes risk. However, it is known that when uncertainty is high there is a stronger correspondence between innovativeness and performance. As uncertainty is high in Africa, this paper claims that it is plausible to find correspondence between innovativeness and performance. This argument is developed since investors typically cope with uncertainty by networking on a reciprocal basis and preferring munificent markets. This link leads us to ask if innovativeness mediates the effect of relatively rich/poor environmental munificence and reciprocal exchange on performance in South Sudan (S. Sudan) and Tanzania. A tested model reveals that four components and an underlying 12 different observations are equivalent across both countries. Furthermore, a tested structural model confirms that the business logic of investors is quite different in S. Sudan and Tanzania. Innovativeness completely mediates effects of reciprocity and munificence on performance in Tanzania but not in S. Sudan. We found some support for the relationship between reciprocity and innovativeness but no support for munificence on innovativeness and performance.
Institutional and Organizational Analysis

What explains the great variability in economic growth and political development across countries? Institutional and organizational analysis has developed since the 1970s into a powerful toolkit, which argues that institutions and norms rather than geography, culture, or technology are the primary causes of sustainable development. Institutions are rules that recognized authorities create and enforce. Norms are rules created by long-standing patterns of behavior, shared by people in a society or organization. They combine to play a role in all organizations, including governments, firms, churches, universities, gangs, and even families. This introduction to the concepts and applications of institutional and organizational analysis uses economic history, economics, law, and political science to inform its theoretical framework. Institutional and organizational analysis becomes the basis to show why the economic and political performance of countries worldwide have not converged, and reveals the lessons to be learned from it for business, law, and public policy.
Do integrated economies grow faster? Evidence from domestic equity holdings

This paper aims to investigate the impact of financial integration on economic growth. Home bias, which is the tendency of over-investing in domestic stock bourse, is proposed as a proxy of advanced financial integration. The persistence of home bias reflects the existence of international friction. A high degree of home bias reflects imperfect integration of the national stock market with world capital markets and suggests a slower pace of economic expansion. Home bias is utilised, through its own lags, to address the reverse causality implied by potential endogeneity between home bias and real GDP growth. A dynamic GMM approach is employed to address the endogeneity and serial correlation concern. The results indicate the lagged real GDP per capita growth, home bias, government consumption, and variability in real effective exchange rates are found to explain cross-country variation in growth.
On the History of Unified Field Theories. Part II. (ca. 1930–ca. 1965)

The present review intends to provide an overall picture of the research concerning classical unified field theory, worldwide, in the decades between the mid-1930 and mid-1960. Main themes are the conceptual and methodical development of the field, the interaction among the scientists working in it, their opinions and interpretations. Next to the most prominent players, A. Einstein and E. Schrödinger, V. Hlavatý and the French groups around A. Lichnerowicz, M. -A. Tonnelat, and Y. Thiry are presented. It is shown that they have given contributions of comparable importance. The review also includes a few sections on the fringes of the central topic like Born-Infeld electromagnetic theory or scalar-tensor theory. Some comments on the structure and organization of research-groups are also made.
Cadherin-Cadherin Engagement Promotes Cell Survival via Rac1/Cdc42 and Signal Transducer and Activator of Transcription-3

Signal transducer and activator of transcription-3 (Stat3) is activated by a number of receptor and nonreceptor tyrosine kinases, whereas a constitutively active form of Stat3 alone is sufficient to induce neoplastic transformation. In the present report, we show that Stat3 can also be activated through homophilic interactions by the epithelial (E)-cadherin. Indeed, by plating cells onto surfaces coated with fragments encompassing the two outermost domains of this cadherin, we clearly show that cadherin engagement can activate Stat3, even in the absence of direct cell-to-cell contact. Most importantly, our results also reveal for the first time an unexpected and dramatic surge in total Rac1 and Cdc42 protein levels triggered by cadherin engagement and an increase in Rac1 and Cdc42 activity, which is responsible for the Stat3 stimulation observed. Inhibition of cadherin interactions using a peptide, a soluble cadherin fragment, or genetic ablation induced apoptosis, points to a significant role of this pathway in cell survival signaling, a finding that could also have important therapeutic implications. (Mol Cancer Res 2009;7(8):1310–27)
Involvement of the Nonhomologous End Joining DNA Repair Pathway in the Bystander Effect for Chromosomal Aberrations

Abstract Little, J. B. , Nagasawa, H. , Li, G. C. and Chen, D. J. Involvement of the Nonhomologous End Joining DNA Repair Pathway in the Bystander Effect for Chromosomal Aberrations. Radiat. Res. 159, 262–267 (2003). Cells of mouse knockout cell lines for Ku80 (now known as Xrcc5), Ku70 (now known as G22p1), DNA-PKcs (now known as Prkdc) and PARP (now known as Adprt) were synchronized in G1 phase and exposed to very low fluences of α particles. The frequency of gross chromosomal aberrations was scored at the first postirradiation metaphase. At the two lowest doses examined, aberrations were induced in 4–9% of wild-type cells and 36–55% of Xrcc5−/− cells, whereas only 2–3% of the nuclei were traversed by an α particle and thus received any radiation exposure. G22p1−/− cells responded similarly to Xrcc5−/− cells, whereas Prkdc−/− and Adprt−/− cells showed an intermediate effect. The frequency of aberrations per nuclear traversal increased approximately 30-fold for Xrcc5−/− and G22p1−/− cells at the lowest mean dose examined (0.17 cGy), compared with 10-fold in Prkdc−/− cells and 3-fold in wild-type cells. Based on these and other findings, we hypothesize that the marked sensitization of repair-deficient bystander cells to the induction of chromosomal aberrations is a consequence of unrejoined DNA double-strand breaks occurring as a result of clustered damage arising from opposed oxidative lesions and single-strand breaks.
Sonoembryology and early prenatal diagnosis of neural anomalies

In the following review, the early development of the central nervous system (CNS), as described by embryologists and anatomists in modern embryological textbooks, is compared with sonoanatomic descriptions from two‐dimensional (2D) and three‐dimensional (3D) ultrasound studies, week by week in the first trimester. The anatomic descriptions are limited to details that are of interest for the understanding of ultrasound examinations. Further, the detection of main CNS anomalies including spina bifida during the first trimester are presented and discussed. Empty or enlarged brain cavities, or abnormal contours of the head and spine are important diagnostic markers for the detection of CNS anomalies in the very early pregnancy. Copyright © 2009 John Wiley & Sons, Ltd.
Cloning of a New Mouse Two-P Domain Channel Subunit and a Human Homologue with a Unique Pore Structure*

Mouse KCNK6 is a new subunit belonging to the TWIK channel family. This 335-amino acid polypeptide has four transmembrane segments, two pore-forming domains, and a Ca2+-binding EF-hand motif. Expression of KCNK6 transcripts is principally observed in eyes, lung, stomach and embryo. In the eyes, immunohistochemistry reveals protein expression only in some of the retina neurons. Although KCNK6 is able to dimerize as other functional two-P domain K+ channels when it is expressed in COS-7 cells, it remains in the endoplasmic reticulum and is unable to generate ionic channel activity. Deletions, mutations, and chimera constructions suggest that KCNK6 is not an intracellular channel but rather a subunit that needs to associate with a partner, which remains to be discovered, in order to reach the plasma membrane. A closely related human KCNK7-A subunit has been cloned. KCNK7 displays an intriguing GLE sequence in its filter region instead of the G(Y/F/L)G sequence, which is considered to be the K+ channel signature. This subunit is alternatively spliced and gives rise to the shorter forms KCNK7-B and -C. None of the KCNK7 structures can generate channel activity by itself. The KCNK7 gene is situated on chromosome 11, in the q13 region, where several candidate diseases have been identified.