Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of human transforming growth factor α by chinese hamster ovarian tumors in nude mice causes hypercalcemia and increased osteoclastic bone resorption

Transforming growth factor α (TGF‐α) is a polypeptide regulator of cell growth produced by many malignant tumors. It stimulates osteoclastic resorption in bone organ culture and osteoclast‐like cell formation in marrow culture. To determine whether tumor production of TGF‐α can cause hypercalcemia in vivo, we used Chinese hamster ovarian (CHO) cells transfected with the human TGF‐α gene (TCHO), which stably express and secrete TGF‐α. We used nontransfected CHO cells as controls (CCHO). TCHO and CCHO were inoculated intramuscularly into one hindlimb of nude mice and grew as local solid tumors. After 4 weeks of TCHO tumor growth, plasma ionized calcium (Ca2+) increased to reach 1.48 ± 0.03 mM (mean ± SEM), whereas mice bearing similarly sized CCHO tumors and non‐tumor‐bearing mice (NTB) remained normocalcemic (normal range for Ca2+, 1.15–1.30 mM). Plasma TGF‐α was undetectable by an ELIFA assay in all NTB mice, was markedly increased in all TCHO mice (5.75 ± 0.78 ng/ml), and was slightly increased in CCHO mice (0.50 ± 0.22 ng/ml). Quantitative bone histomorphometry showed a prominent increase in osteoclastic bone resorption in TCHO mice. These data suggest that TGF‐α is a mediator of hypercalcemia and increased osteoclastic bone resorption in tumors that produce it in sufficient quantity.
Importance of intraoperative magnetic resonance imaging for pediatric brain tumor surgery

Background: High-field intraoperative MRI (IoMRI) is gaining increasing recognition as an invaluable tool in pediatric brain tumor surgery where the extent of tumor resection is a major prognostic factor. We report the initial experience of a dedicated pediatric 3-T intraoperative MRI (IoMRI) unit with integrated neuronavigation in the management of pediatric brain tumors. Methods: Seventy-three children (mean age 9.5 years; range 0.2–19 years) underwent IoMRI between October 2009 and January 2012, during 79 brain tumor resections using a 3-T MR scanner located adjacent to the neurosurgical operating theater that is equipped with neuronavigation facility. IoMRI was performed either to assess the extent of tumor resection after surgical impression of complete/intended tumor resection or to update neuronavigation. The surgical aims, IoMRI findings, extent of tumor resection, and follow-up data were reviewed. Results: Complete resection was intended in 47/79 (59%) operations. IoMRI confirmed complete resection in 27/47 (57%). IoMRI findings led to further resection in 12/47 (26%). In 7/47 (15%), IoMRI was equivocal for residual tumor and no evidence of residual tumor was found on re-inspection. In 32/79 (41%) operations, the surgical aim was partial tumor resection. In this subset, surgical resection was extended following IoMRI in 13/32 (41%) operations. None of the patients required early second look procedure for residual disease. Conclusions: At our institution, IoMRI has led to increased rate of tumor resection and a change in surgical strategy with further tumor resection in 32% of patients. While interpreting IoMRI, it is important to be aware of the known pitfalls.
Effect of renin–angiotensin–aldosterone system blockade in adults with diabetes mellitus and advanced chronic kidney disease not on dialysis: a systematic review and meta-analysis

The presumed superiority of renin-angiotensin-aldosterone system (RAAS)-blocking agents over other antihypertensive agents in patients with diabetes to delay development of end-stage kidney disease (ESKD) has recently been challenged. In addition, there is ongoing uncertainty whether RAAS-blocking agents reduce mortality and/or delay ESKD in patients with diabetes and chronic kidney disease (CKD) stages 3-5. In this subgroup, there might be an expedited need for renal replacement therapy (RRT) when RAAS-blocking agents are used. We conducted a meta-analysis of randomized controlled trials (RCTs) of at least 6-months duration in adult patients with diabetes who also have non-dialysis CKD stages 3-5. RCTs comparing single RAAS-blocking agents to placebo or alternative antihypertensive agents were included. Outcomes of interest were all-cause mortality, cardiovascular morbidity, progression of renal function, ESKD and adverse events. A total of nine trials (n = 9797 participants with CKD stages 3-5) fit our inclusion criteria. There was no difference between the RAAS group and control group regarding all-cause mortality {relative risk [RR] = 0.97 [95% confidence interval (CI) 0.85-1.10]}, cardiovascular mortality [RR = 1.03 (95% CI 0.75-1.41)] and adverse events [RR = 1.05 (95% CI 0.89-1.25)]. There was a trend for a favourable effect for non-fatal cardiovascular events [RR = 0.90 (95% CI 0.81-1.00)] and a lower risk of the composite endpoint need for RRT/doubling of serum creatinine [RR = 0.81 (95% CI 0.70-0.92)] in the RAAS-blocking agents group versus the control group. We found evidence that in patients with diabetes mellitus and CKD stages 3-5, treatment with RAAS-blocking agents did not result in a clear survival advantage. The effect on renal outcomes did depend on the selected outcome measure. However, we did not find evidence that the use of RAAS-blocking agents expedited the need for RRT in patients with CKD stages 3-5.
Molecular characterization of Celtix‐1, a bromodomain protein interacting with the transcription factor interferon regulatory factor 2

Transcriptional control at the G1/S‐phase transition of the cell cycle requires functional interactions of multimeric promoter regulatory complexes that contain DNA binding proteins, transcriptional cofactors, and/or chromatin modifying enzymes. Transcriptional regulation of the human histone H4/n gene (FO108) is mediated by Interferon Regulatory Factor‐2 (IRF‐2), as well as other histone gene promoter factors. To identify proteins that interact with cell‐cycle regulatory factors, we performed yeast two‐hybrid analysis with IRF‐2 and identified a novel human protein termed Celtix‐1 which binds to IRF‐2. Celtix‐1 contains several phylogenetically conserved domains, including a bromodomain, which is found in a number of transcriptional cofactors. Using a panel of IRF‐2 deletion mutants in yeast two‐hybrid assays, we established that Celtix‐1 contacts the C‐terminus of IRF‐2. Celtix‐1 directly interacts with IRF‐2 based on binding studies with glutathione S‐transferase (GST)/IRF‐2 fusion proteins, and immunofluorescence studies suggest that Celtix‐1 and IRF‐2 associate in situ. Celtix‐1 is distributed throughout the nucleus in a heterodisperse pattern. A subset of Celtix‐1 colocalizes with the hyperacetylated forms of histones H3 and H4, as well as with the hyperphosphorylated, transcriptionally active form of RNA polymerase II. We conclude that the bromodomain protein Celtix‐1 is a novel IRF‐2 interacting protein that associates with transcriptionally active chromatin in situ. J. Cell. Physiol. 185:269–279, 2000. © 2000 Wiley‐Liss, Inc.
The Netherlands: A heartland full of insights into populist communication

Populism has played a pivotal role in the Dutch political landscape since the 2000s. The rise and rapid decline of Pim Fortuyn’s right-wing populist party Lijst Pim Fortuyn (LPF) in 2002 marks the start of inuential Dutch populism (Schafraad, Scheepers, & Wester, 2010). Although the party’s success was short-lived, Lijst Pim Fortuyn was the rst populist party that managed to obtain a large share of the vote in the national elections, eventually winning 26 seats in parliament. After Fortuyn’s death in 2002, Dutch politics witnessed a few relatively quiet years, with a quarreling Lijst Pim Fortuyn and several offshoots of Fortuyn’s party, such as One Netherlands and the Party for the Netherlands. Successful populism re-entered the stage with Wilders’ Freedom Party (PVV) in 2005. In 2010, the Freedom Party even became the third largest party in the general elections, winning 24 seats in parliament. During the last decade, various populist parties such as Verdonk’s right-wing Proud of the Netherlands (ToN) and the 50Plus Party (for the senior population) entered the political stage in the slipstream of Lijst Pim Fortuyn and the Freedom Party, albeit with less electoral success.
Subclavian Venous Catheterization in Children

During a 12‐month period, infraclavicular subclavian catheterization, using a Seldinger technique, was attempted on 77 occasions in 54 children with a median age of 2 years (range newborn to 10 years). General anaesthesia was used in the majority of cases, and catheterization was successful in 74 cases (96%). The initial catheter tip position was satisfactory in 81% of the cases, and catheters remained in situ for a median period of 7 days (range 1–28 days). There were few complications. Providing extensive experience in subclavian venous cannulation is gained in the adult, there is in our experience no minimal age or size which should limit the use of a subclavian vein catheter.
A prospective randomized study of use of drain versus no drain after burr-hole evacuation of chronic subdural hematoma.

OBJECTIVE Chronic subdural hematoma (CSDH) recurs after surgical evacuation in 5-30% of patients. Inserting subdural drain might reduce the recurrence rate, but is not commonly practiced. There are few prospective studies to evaluate the effect of subdural drains. MATERIALS AND METHODS A prospective randomized study to investigate the effect of subdural drains in the on recurrence rates and clinical outcome following burr-hole drainage (BHD) of CSDH was undertaken. During the study period, 246 patients with CSDH were assessed for eligibility. Among 200 patients fulfilling the eligibility criteria, 100 each were assigned to "drain group" (drain inserted into the subdural space following BHD) and "without drain group" (subdural drain was not inserted following BHD) using random allocation software. The primary end point was recurrence needing re-drainage up to a period of 6 months from surgery. RESULTS Recurrence occurred in 9 of 100 patients with a drain, and 26 of 100 patients in without drain group (P = 0.002). The mortality was 5% in patients with drain and 4% in patients without drain group (P = 0.744). The medical and surgical complications were comparable between the two study groups. CONCLUSION Use of a subdural drain after burr-hole evacuation of a CSDH reduces the recurrence rate and is not associated with increased complications.
Resection of a Pontine Cavernous Malformation via an Endoscopic Endonasal Approach: A Case Report

BACKGROUND AND IMPORTANCE: Cavernous malformations of the brainstem are a dilemma in terms of deciding when to operate, and they remain difficult to access surgically. We present a novel approach for the resection of a brainstem cavernous malformation CLINICAL PRESENTATION: A 59-year-old woman presented with a 1-month history of intermittent dysarthria, right facial weakness, and left arm and leg weakness. A magnetic resonance image revealed a 2-cm mass in the pons with blood products of differing ages, consistent with a cavernous malformation. We discussed with her the risks of surgical resection and conservative management. She decided to pursue conservative management. Two weeks later, she returned to the emergency room with diplopia and left-sided hemiplegia. Acute hemorrhage within the right pons was seen. She then chose to undergo surgical resection. CONCLUSION: The patient underwent an endoscopic transnasal approach for resection of a pontine cavernous malformation. Image guidance was used to identify key anatomic landmarks. A gross total resection was achieved without new neurological deficits. With physical and occupational therapy, the patient developed antigravity strength in her left upper and lower extremities before discharge. At her 4-week follow-up, she was ambulating independently with the assistance of a cane. We report the successful gross total resection of a pontine cavernous malformation via an endoscopic transnasal approach. This patient had improvement in neurological symptoms after surgical resection with minimal surgical morbidity. Technologic advances in endoscopic skull base approaches have provided access to lesions of the skull base previously requiring more invasive approaches.
Impact of Macroeconomic Factors on Underpricing of Initial Public Offerings before and after the Recent Global Financial Crisis: Evidence from Istanbul Stock Exchange

Underpricing of Initial Public Offerings (IPO) has always been a big deal to see the money left on the table by the issuers. This study analyzes the after-market performances of IPOs observed in 2006-2011 period in Istanbul Stock Exchange (ISE). Besides looking at the period as a whole, we divide that period into three regarding the Eight Annual Ernst & Young Global IPO Trends. This gives the opportunity to analyze the impact of macroeconomic factors before financial crisis (2006-2007), during the financial crisis (2008-2009), and after the financial crisis (2010-2011). There are 33 IPOs in 2006-2007 period, 8 IPOs in 2008-2009 period and 53 IPOs between 2009 and 2010. We use multiple regression analysis to discover the effects of the macroeconomic factors as ISE 100 index, consumer price index, consumer confidence index, interest rate, world oil price, GDP per capita on the first day performances of IPOs.
Restoration of impaired phosphorylation of cyclic AMP response element‐binding protein (CREB) by EGb 761 and its constituents in Aβ‐expressing neuroblastoma cells

Cyclic AMP response element‐binding protein (CREB) plays important roles in neuronal plasticity and amyloid β‐peptide (Aβ)‐induced cognitive impairment in Alzheimer's disease (AD). Here we demonstrated that Ginkgo biloba extract, EGb 761, displayed the neuron protective effect by activating the CREB signaling pathway. Wild‐type neuroblastoma cells cultured in a conditioned medium containing cell‐secreted Αβ exhibited reduced levels of phosphorylated CREB (pCREB). Addition of EGb 761 (100 µg/mL) or an anti‐oligomer‐specific antibody (A‐11) to the conditioned medium could restore pCREB level. In a neuroblastoma cell line expressing Αβ, treatment with EGb 761 increased levels of pCREB and brain‐derived neurotrophic factor. Furthermore, CREB phosphorylation induced by EGb 761 was blocked by inhibitors of several upstream signaling pathways of CREB, including protein kinase C, ERK, ribosomal S6 kinase(RSK)90 and nitric oxide pathway. Moreover, these inhibitors differentially blocked the effects of individual components of EGb 761, ginkgolide C, quercetin and bilobalide, which suggest diverse effects of the EGb 761 individual components. Actions of individual EGb 761 components provide further insights into direct mechanisms underlying the effect of EGb 761 on enhancing the cognitive performance of patients with AD.
Neuromuscular Diseases Associated With Chronic Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection is a growing international health problem, and more than 170 million people are chronic carriers. Up to 50% of HCV-positive patients develop at least one extrahepatic manifestation during the course of disease. To varying degrees of certainty, there is evidence of an association between chronic HCV infection and a variety of neuromuscular diseases. The pathogenesis of most extrahepatic diseases remains unclear but possibly includes HCV lymphotropism and/or HCV-induced autoantibodies. The therapeutic approach to HCV-associated autoimmune disorders entails eradication of HCV with one of the recombinant interferon-alpha preparations with or without additional immunosuppressive drugs.
Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls

Background Voluntary lumbopelvic control is compromised in patients with back pain. Loss of proprioceptive acuity is one contributor to decreased control. Several reasons for decreased proprioceptive acuity have been proposed, but the integrity of cortical body maps has been overlooked. We investigated whether tactile acuity, a clear clinical signature of primary sensory cortex organisation, relates to lumbopelvic control in people with back pain. Methods Forty-five patients with back pain and 45 age- and sex-matched healthy controls participated in this cross-sectional study. Tactile acuity at the back was assessed using two-point discrimination (TPD) threshold in vertical and horizontal directions. Voluntary motor control was assessed using an established battery of clinical tests. Results Patients performed worse on the voluntary lumbopelvic tasks than healthy controls did (p<0.001). TPD threshold was larger in patients (mean (SD)=61 (13) mm) than in healthy controls (44 (10) mm). Moreover, larger TPD threshold was positively related to worse performance on the voluntary lumbopelvic tasks (Pearson's r=0.49; p<0.001). Discussion Tactile acuity, a clear clinical signature of primary sensory cortex organisation, relates to voluntary lumbopelvic control. This relationship raises the possibility that the former contributes to the latter, in which case training tactile acuity may aid recovery and assist in achieving normal motor performance after back injury.
Market calibration under a long memory stochastic volatility model

ABSTRACT In this article, we study a long memory stochastic volatility model (LSV), under which stock prices follow a jump-diffusion stochastic process and its stochastic volatility is driven by a continuous-time fractional process that attains a long memory. LSV model should take into account most of the observed market aspects and unlike many other approaches, the volatility clustering phenomenon is captured explicitly by the long memory parameter. Moreover, this property has been reported in realized volatility time-series across different asset classes and time periods. In the first part of the article, we derive an alternative formula for pricing European securities. The formula enables us to effectively price European options and to calibrate the model to a given option market. In the second part of the article, we provide an empirical review of the model calibration. For this purpose, a set of traded FTSE 100 index call options is used and the long memory volatility model is compared to a popular pricing approach – the Heston model. To test stability of calibrated parameters and to verify calibration results from previous data set, we utilize multiple data sets from NYSE option market on Apple Inc. stock.
Erythropoietin directly stimulates osteoclast precursors and induces bone loss

Erythropoietin (EPO) primarily regulates red blood cell formation, and EPO serum levels are increased on hypoxic stress (e.g., anemia and altitude). In addition to anemia, recent discoveries suggest new therapeutic indications for EPO, unrelated to erythropoiesis. We investigated the skeletal role of EPO using several models of overexpression (Tg6 mice) and EPO administration (intermittent/continuous, high/low doses) in adult C57B16 female mice. Using microcomputed tomography, histology, and serum markers, we found that EPO induced a 32%‐61% trabecular bone loss caused by increased bone resorption (+60%‐88% osteoclast number) and reduced bone formation rate (‐19 to ‐74%; P < 0.05 throughout). EPO targeted the monocytic lineage by increasing the number of bone monocytes/macrophages, preosteoclasts, and mature osteoclasts. In contrast to the attenuated bone formation in vivo, EPO treatment in vitro did not inhibit osteoblast differentiation and activity, suggesting an indirect effect of EPO on osteoblasts. However, EPO had a direct effect on preosteoclasts by stimulating osteoclastogenesis in isolated cultures (+60%) via the Jak2 and PI3K pathways. In summary, our findings demonstrate that EPO negatively regulates bone mass and thus bears significant clinical implications for the potential management of patients with endogenously or therapeutically elevated EPO levels. —Hiram‐Bab, S. , Liron, T. , Deshet‐Unger, N. , Mittelman, M. , Gassmann, M. , Rauner, M. , Franke, K. , Wielockx, B. , Neumann, D. , Gabet, Y. Erythropoietin directly stimulates osteoclast precursors and induces bone loss. FASEB J. 29, 1890‐1900 (2015). www.fasebj. org
A 60GHz CMOS phased-array transceiver pair for multi-Gb/s wireless communications

Recent advances in silicon technology, mm-Wave integrated circuit/antenna/package design, and beam-forming techniques at 60GHz, together with the emergence of suitable wireless standards, have enabled consumer electronics products to support wireless transmission of multi-Gb/s data such as high-definition (HD) audio/video content [1,2]. Further expansion into portable and mobile platforms will require lower power consumption, smaller form factor, and lower cost. This paper describes a fully integrated, low-cost 60GHz phased-array transceiver pair, implemented in 65nm standard digital CMOS and packaged with an embedded antenna array, capable of robust 10m non-line of sight (NLOS) communication. The array is configurable from 32 elements to 8 or fewer elements, making the transceiver pair suitable for both fixed, high-data-rate and portable, low-power applications. To enhance the robustness of the multi-element design, dynamic phase shifters allow the beam direction to be changed in real time to adapt to changing environments without interruption of the multi-Gb/s data stream. The transceiver pair supports the WirelessHD and draft 802.11ad (WiGig) standards at maximum data rates of 7.14Gb/s and 6.76Gb/s, respectively.
Path- and place-dependence of entrepreneurial ventures at times of war and conflict

Studies have previously examined the path-development of entrepreneurs within a penurious environment, but what if their path encounters a conflict situation? Does conflict engender greater resource poverty and subsequently msqueeze out any remaining life from entrepreneurism? Utilising Isaksen’s characterisation of path-dependence, we examine how entrepreneurs negotiate their path through the ‘double whammy’ of penurious environment and conflict. Through an event-based approach examining the entrepreneurial paths of three wartime entrepreneurs, our study indicates that while the immediate aftermath is chaos leading to limited path-extension and even path-exhaustion, once initial challenges are addressed, entrepreneurial individuals find different ways to adapt, not only through path-extension but also through path-renewal and path-creation. These opportunities are place-dependent, the recognition of which requires considerable local knowledge and resources acquired through experience and prior local investment as well as interdependent networks.