Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical profile and treatment outcome of chronic pancreatitis in children: a long-term follow-up study of 156 cases

Abstract Aim: There is a paucity of literature in pediatric chronic pancreatitis (CP) and most information is derived from adult literature. We, therefore, analyzed our experience of CP to look for clinical profile and long-term outcome. Methods: From January 2003 to December 2015, 156 consecutive children (≤18 years) diagnosed as CP were included. Their clinical profile, management, and follow-up data were retrieved. Genetic markers (PRSS1, SPINK1, and CFTR) were studied in 40 idiopathic cases. Results: The median age of the patients was 13 [inter-quartile range (IQR): 10–14] years (93 males) and 134 (86%) were idiopathic. Genetic mutations were found in 22/40 (55%) idiopathic cases. All but two presented with pain abdomen (episodic pain in 93.6%) and symptom duration was 12 (IQR: 6–24) months. There were two subsets; calcific (CCP) 68 (43.5%) and non-calcific (NCCP) 88 (56.5%). In CCP group, significantly more children had Cambridge grade 5 magnetic resonance cholangiopancreatography changes, low weight Z-score, and had continuous pain more compared to NCCP group. Over a median follow-up of 23 (IQR: 8–45.5) months, more children in CCP group had complications. Endoscopic therapy (done for persistent pain in 40) relieved pain in 52.5% of cases while medical therapy did so in 36% of cases. Conclusion: Pediatric CP in Asia presents with episodic pain and genetic predisposition seems to be a major cause. There are two subsets; CCP and NCCP with former showing marked imaging changes, more often associated with malnutrition and complications. Endoscopic therapy for pain relief gives modest benefit but medical therapy is not encouraging.
Craniosynostosis : Updates in Radiologic Diagnosis

The purpose of this article is to review imaging findings and to discuss the optimal imaging methods for craniosynostosis. The discussion of imaging findings are focused on ultrasonography, plain radiography, magnetic resonance imaging and computed tomography with 3-dimensional reconstruction. We suggest a strategy for imaging work-up for the diagnosis, treatment planning and follow-up to minimize or avoid ionized radiation exposure to children by reviewing the current literature.
Liquidity Risk, Credit Risk and the Overnight Interest Rate Spread: A Stochastic Volatility Modelling Approach

In this paper we model the volatility of the spread between the overnight interest rate and the central bank policy rate (the policy spread) for the euro area and the UK during the two main phases of the financial crisis that began in late 2007. During the crisis, the policy spread exhibited signs of volatility, owing to the breakdown in interbank market activity. The determinants of this volatility are assessed using Stochastic Volatility models to gauge the role played by liquidity risk, credit risk (financial and sovereign), and interest rate expectations. Our results suggest that liquidity risk is the main determinant of the volatility of the policy spread, but also that private bank credit risk has become more apparent in the post-Lehman collapse phase of the crisis for the euro area as financial CDS premia rose due to possible default fears. In addition, the ECB appears to have been more effective in addressing liquidity risk since the onset of the crisis, and this may be related to its greater direct access to a broader range of counterparties and its acceptance of a broader range of eligible collateral. The main implication is that, in crisis times, a sufficiently flexible operational framework for monetary policy implementation produces the most timely response to market tensions.
Analgesic Compound from Sea Anemone Heteractis crispa Is the First Polypeptide Inhibitor of Vanilloid Receptor 1 (TRPV1)*

Venomous animals from distinct phyla such as spiders, scorpions, snakes, cone snails, or sea anemones produce small toxic proteins interacting with a variety of cell targets. Their bites often cause pain. One of the ways of pain generation is the activation of TRPV1 channels. Screening of 30 different venoms from spiders and sea anemones for modulation of TRPV1 activity revealed inhibitors in tropical sea anemone Heteractis crispa venom. Several separation steps resulted in isolation of an inhibiting compound. This is a 56-residue-long polypeptide named APHC1 that has a Bos taurus trypsin inhibitor (BPTI)/Kunitz-type fold, mostly represented by serine protease inhibitors and ion channel blockers. APHC1 acted as a partial antagonist of capsaicin-induced currents (32 ± 9% inhibition) with half-maximal effective concentration (EC50) 54 ± 4 nm. In vivo, a 0.1 mg/kg dose of APHC1 significantly prolonged tail-flick latency and reduced capsaicin-induced acute pain. Therefore, our results can make an important contribution to the research into molecular mechanisms of TRPV1 modulation and help to solve the problem of overactivity of this receptor during a number of pathological processes in the organism.
Nervous control of ciliary beating by Cl-, Ca2+ and calmodulin in Tritonia diomedea

SUMMARY In vertebrates, motile cilia line airways, oviducts and ventricles. Invertebrate cilia often control feeding, swimming and crawling, or gliding. Yet control and coordination of ciliary beating remains poorly understood. Evidence from the nudibranch mollusc, Tritonia diomedea, suggests that locomotory ciliated epithelial cells may be under direct electrical control. Here we report that depolarization of ciliated pedal epithelial (CPE) cells increases ciliary beating frequency (CBF), and elicits CBF increases similar to those caused by dopamine and the neuropeptide, TPep-NLS. Further, four CBF stimulants (zero external Cl-, depolarization, dopamine and TPep-NLS) depend on a common mode of action, viz. Ca2+ influx, possibly through voltage-gated Ca2+ channels, and can be blocked by nifedipine. Ca2+ influx alone, however, does not provide all the internal Ca2+ necessary for CBF change. Ryanodine receptor (RyR) channel-gated internal stores are also necessary for CBF excitation. Caffeine can stimulate CBF and is sensitive to the presence of the RyR blocker dantrolene. Dantrolene also reduces CBF excitation induced by dopamine and TPep-NLS. Finally, W-7 and calmidazolium both block CBF excitation by caffeine and dopamine, and W-7 is effective at blocking TPep-NLS excitation. The effects of calmidazolium and W-7 suggest a role for Ca2+-calmodulin in regulating CBF, either directly or via Ca2+-calmodulin dependent kinases or phosphodiesterases. From these results we hypothesize dopamine and TPep-NLS induce depolarization-driven Ca2+ influx and Ca2+ release from internal stores that activates Ca2+-calmodulin, thereby increasing CBF.
Pupil responses to foveal exchange of monochromatic lights.

Temporal exchanges of equiluminant monochromatic lights of different spectral distributions produced a momentary constriction of the pupil in man. This is not a stimulus artifact because exchanges of two lights with identical distributions in the same apparatus produced no response. Responses evoked by rod signals were successfully obviated by presenting the foveal stimulus inside a large rod saturating annulus. The amplitude of the response varied systematically with stimulus wavelength. The exchange of a standard light to either shorter or longer wavelength lights produced a momentary constriction of the pupil; the greater the wavelength difference (between them); the larger the constriction. This ability to respond to exchanges of one spectral distribution for another is not a consequence of chromatic aberration or chromatic differences in magnification. Chromatic exchanges between lights of equal chromatic aberration do not produce identical pupillary response in deuteranopes: The exchange 560 nm→650 nm produced no pupil response, while the 560 nm→498 nm exchange produced a sizable response. Exchange of equally luminant heterochromatic lights evoked a response with 50 ms longer latency than the same amplitude constriction evoked by a step increase in luminance of a homochromatic light. The homochromatic contrast needed to evoke the same constriction as a given equal luminance heterochromatic exchange closely follows the homochromatic contrast which matched the residual flicker in flicker photometry of that same wavelength pair.
Up-Regulation of Regulator of G Protein Signaling 4 Expression in a Model of Neuropathic Pain and Insensitivity to Morphine

We hypothesized that the up-regulated expression of one or more members of the regulator of G protein signaling (RGS) family can cause an attenuation of signaling via Gi/Go-coupled opioid receptors, and thereby play a role in the development of hyperalgesia and accompanying insensitivity to morphine observed in animal models of neuropathic pain. Accordingly, we examined the mRNA expression of several RGS genes in a rat model of chronic neuropathic pain induced by partial ligation of the sciatic nerve. During the development of hyperalgesia, RGS4 was the only isoform examined whose mRNA levels increased significantly (up to 230%) in the lumbar spinal cord. In situ hybridization studies confirmed that RGS4 is present in the dorsal horn of the spinal cord where μ-opioid receptors (MORs) are also expressed. Overexpression of RGS4 in human embryonic kidney 293 cells stably expressing μ-opioid receptors predictably attenuated opioid agonist-induced inhibition of adenylyl cyclase. This inhibitory effect was overcome partially at high agonist concentrations, supporting the view that morphine insensitivity is promoted by RGS4 overexpression. These studies provide evidence that the up-regulation of RGS4 expression may contribute to changes in pain signal processing that lead to the development of hyperalgesia, and further affect its modulation by morphine.
A FRAMEWORK FOR MEASURING HAPPINESS IN ONLINE SOCIAL NETWORKS

Research on happiness has been conducted for many decades with various interesting results reported by different groups of researchers. While there is a plethora of research efforts on happiness in general, there is little work being done to study the effects of online social networks on happiness. This is mainly due to the relative (in)maturity of online social networking as it has only been around for the last few years. This research attempts to answer if the offline social network phenomenon can be carried towards its online social network counterpart such as Facebook and MySpace, both of which have millions of active users. This paper describes the first phase of the research, where a framework for modeling happiness from a more comprehensive perspective is presented. A multi-dimensional happiness measure is developed based on Ryff‟s well-being theory [8] and its reliability and validity are discussed in this paper.
Information hiding-a survey

Information-hiding techniques have recently become important in a number of application areas. Digital audio, video, and pictures are increasingly furnished with distinguishing but imperceptible marks, which may contain a hidden copyright notice or serial number or even help to prevent unauthorized copying directly. Military communications systems make increasing use of traffic security techniques which, rather than merely concealing the content of a message using encryption, seek to conceal its sender, its receiver, or its very existence. Similar techniques are used in some mobile phone systems and schemes proposed for digital elections. Criminals try to use whatever traffic security properties are provided intentionally or otherwise in the available communications systems, and police forces try to restrict their use. However, many of the techniques proposed in this young and rapidly evolving field can trace their history back to antiquity, and many of them are surprisingly easy to circumvent. In this article, we try to give an overview of the field, of what we know, what works, what does not, and what are the interesting topics for research.
End-to-end Congestion Control for Flows with Variable Packet Size

Current TCP-friendly congestion control mechanisms such as those used in TFRC adjust the packet rate in order to adapt to network conditions and obtain a throughput not exceeding that of a TCP connection operating under the same conditions. In an environment where the bottleneck resource is packet processing, this is the correct behavior. However, if the bottleneck resource is bandwidth, and flows may use packets of different sizes, resource sharing then depends on packet size and is no longer fair. Now for some applications, such as Internet telephony, it is more natural to adjust the packet size, while keeping the packet rate as constant as possible. In this paper we study the impact of variations in packet size on equation-based congestion control and propose methods to remove the throughput bias resulting from the use of different packet sizes. We investigate in detail the design space of the approaches by means of mathematical analysis and propose a number of possible designs. We evaluate these designs through simulation and conclude with some concrete proposals. Our findings can be used to design a TCP-friendly congestion control mechanism for applications that adjust packet size rather than rate, or that are forced to use a small packet size. We base our analysis on the TFRC protocol, but similar considerations also hold for other congestion control mechanisms.
Preterm infants’ behaviors and skin conductance responses to nurse handling in the NICU

Abstract Stress response patterns are indicative of the neonate's unique ability to cope with environmental demands and can be evaluated through autonomic and behavioral response parameters. Objective: To characterize stress responses during tactile stimulation to standard nurse handling in the NICU, and their association with severity of illness in preterm infants. Methods: Thirty preterm neonates were studied at postnatal day 4–5 during standard nurse caregiving. Heart rate (HR), respiratory rate (RR), skin conductance responses per second (SCR/s), and NIDCAP® stress behaviors were recorded before and during care. Non-parametric tests were used to assess differences from before to during care. Pearson’s correlations were used to determine the association of biological and behavioral variables to the score for neonatal acute physiology (SNAP), a severity of illness index. Results: HR, RR, SCR/s and NIDCAP® behaviors (motor and attentional cues, and ability to self-console) increased from before to during the care (p < 0.01). NIDCAP® behaviors showed a significant negative association to the SNAP score (R = −0.45, p < 0.05). Conclusions: HR, RR, SCR/s and NIDCAP® behaviors significantly increased during care. NIDCAP® stress behaviors were influenced by the severity of illness of the infant, while SCR/s was not influenced by severity of illness.
Elevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease

BackgroundElevated C-reactive protein (CRP) serum levels, an exquisitely sensitive objective marker of inflammation, relate to long-term prognosis in patients with coronary artery disease and in apparently healthy men. Because abnormalities of endothelial regulation of vascular function may contribute to the occurrence of coronary events, we tested the hypothesis that elevated CRP levels are associated with an abnormal systemic endothelial vascular reactivity. Methods and ResultsEndothelium-dependent (10 to 50 &mgr;g/min acetylcholine) and endothelium-independent (2 to 8 &mgr;g/min sodium nitroprusside) forearm blood flow responses were measured with venous occlusion plethysmography in 60 male patients with angiographically documented coronary artery disease. Forearm blood flow responses to acetylcholine were inversely correlated with CRP serum levels (r =−0.46, P =0.001). With multivariate analysis that included the classic risk factors for coronary artery disease, elevated CRP serum level remained a statistically significant independent predictor of a blunted endothelial vasodilator capacity. Most important, normalization of elevated CRP levels over time was associated with a normalization of endothelium-mediated forearm blood flow responses after 3 months. ConclusionsThus, elevated CRP serum levels indicative of a systemic inflammatory response are associated with a blunted systemic endothelial vasodilator function. The identification of elevated CRP levels as a transient independent risk factor for endothelial dysfunction might provide an important clue to link a systemic marker of inflammation to atherosclerotic disease progression.
Exogenous Hydrogen Sulfide (H2S) Reduces Blood Pressure and Prevents the Progression of Diabetic Nephropathy in Spontaneously Hypertensive Rats

The coexistence of hypertension and diabetes results in the rapid development of nephropathy. Hydrogen sulfide (H2S) is claimed to control the vascular and renal functions. This study tested the hypothesis that exogenous H2S lowers the blood pressure and decreases the progression of nephropathy in spontaneously hypertensive rats (SHR) that were diabetic. Eighteen SHR were divided into three groups: SHR, SHR diabetic, and SHR diabetic treated with a group of Wistar–Kyoto rats serving as normotensive nondiabetic control. Diabetes was induced with streptozotocin (STZ) in two groups and one diabetic group received sodium hydrosulfide (NaHS), a H2S donor for 5 weeks. Blood pressure was measured in conscious and anesthetized states and renal cortical blood perfusion in acute studies. Plasma and urinary H2S levels, creatinine concentrations, and electrolytes were measured on three different occasions throughout the 35-day period. Diabetic SHR had higher blood pressure, lower plasma and urinary H2S levels, and renal dysfunction as evidenced by increased plasma creatinine, creatinine clearance, and decreased urinary sodium-to-potassium ratio and renal cortical blood perfusion. NaHS reduced blood pressure, increased H2S levels in plasma and urinary excretion, and reversed the STZ-induced renal dysfunction. The findings of this study suggest that the administration of exogenous H2S lowers the blood pressure and confers protection against the progression of STZ-induced nephropathy in SHR.
Transforming Constructivist Learning into Action: Design Thinking in Education.

In an ever changing society of the 21st century, there is a demand to equip students with meta competences going beyond cognitive knowledge. Education, therefore, needs a transition from transferring knowledge to developing individual potentials with the help of constructivist learning. Advantages of constructivist learning, and criteria for its realisation have been well-determined through theoretical findings in pedagogy (Reich 2008, de Corte, OECD 2010). However, the practical implementation leaves a lot to be desired (Gardner 2010, Wagner 2011). Knowledge acquisition is still fragmented into isolated subjects. Lesson layouts are not efficiently designed to help teachers execute a holistic and interdisciplinary learning. As is shown in this paper, teachers are having negative classroom experience with project work or interdisciplinary teaching, due to a constant feeling of uncertainty and chaos, as well as lack of a process to follow. We therefore conclude: there is a missing link between theoretical findings and demands by pedagogy science and its practical implementation. We claim that, Design Thinking as a team-based learning process offers teachers support towards practice-oriented and holistic modes of constructivist learning in projects. Our case study confirms an improvement of classroom experience for teacher and student alike when using Design Thinking. This leads to a positive attitude towards constructivist learning and an increase of its implementation in education. The ultimate goal of this paper is to prove that Design Thinking gets teachers empowered to facilitate constructivist learning in order to foster 21st century skills.
Metastasis‐associated in colon cancer 1 is an independent prognostic biomarker for survival in klatskin tumor patients

Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or orthotopic liver transplantation. However, not all patients benefit from a surgical approach and suffer from early tumor recurrence. Response to chemotherapy is generally poor and, until today, no targeted therapy could be established. Metastasis‐associated in colon cancer 1 (MACC1) is a recently discovered regulator of the hepatocyte growth factor (HGF)/Met/mitogen‐activated protein kinase pathway, which induces proliferation, migration, and invasion in cell culture, as well as metastasis in mice. MACC1 expression shows a significant correlation with Met expression in colon cancer tissue and is highly prognostic for occurrence of distant metastasis and survival in colon cancer patients. Thus, we aimed to measure the expression of MACC1, Met, and HGF messenger RNA in microdissected tumor tissue and corresponding normal liver tissue of 156 patients with Klatskin tumors (n = 76) and ICC (n = 80) using real‐time quantitative reverse‐transcriptase polymerase chain reaction. We used immunohistochemical staining to validate the results. MACC1 expression in tumor tissue of both tumor entities was significantly higher than in corresponding normal liver tissue (P < 0.001). Klatskin tumor patients with a history of tumor recurrence had significantly higher MACC1 expression than those without tumor recurrence (P = 0.005). Uni‐ und multivariate survival analysis showed that Klatskin tumor patients with high MACC1 had a significantly shorter overall (OS) and disease‐free survival (DFS; P = 0.001 and P < 0.001, respectively). The multivariate analysis confirmed MACC1 to be an independent factor for overall survival in Klatskin tumor patients (hazard ratio: 2.777; 95% confidence interval: 1.389‐5.555; P = 0.004). Conclusion: Our study identified MACC1 as a highly prognostic biomarker for OS and DFS in Klatskin tumor patients. MACC1 expression could become an important diagnostic tool and might be a candidate for targeted therapy. (Hepatology 2015;62:841–850)
Characterizing Cannabinoid CB 2 Receptor Ligands Using DiscoveRx PathHunter™ β-Arrestin Assay

The authors have characterized a set of cannabinoid CB2 receptor ligands, including triaryl bis sulfone inverse agonists, in a cell-based receptor/β-arrestin interaction assay (DiscoveRx PathHunter™). The results were compared with results using a competitive ligand binding assay, and with effects on forskolin-stimulated cAMP levels (PerkinElmer LANCE™). The authors show good correlation between the 3 assay systems tested, with the β-arrestin protein complementation assay exhibiting a more robust signal than the cAMP assay for cannabinoid CB2 agonists. Further assay validation shows that DiscoveRx PathHunter™ HEK293 CB2 β-arrestin assay can be carried out from cryopreserved cell suspensions, eliminating variations caused by the need for multiple cell pools during live cell screening campaigns. These results, and the authors' results evaluating a test set of random library compounds, validate the use of ligand-induced interaction between the human cannabinoid CB2 receptor and β-arrestin as an appropriate and valuable screening platform for compounds specific for the cannabinoid CB2 receptor. (Journal of Biomolecular Screening 2009:49-58)