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Clouds are key to understanding the atmosphere and climate, and a long series of satellite observations provide invaluable information to study their properties. EUMETSAT has published Release 1 of the Optimal Cloud Analysis (OCA) Climate Data Record (CDR), which provides a homogeneous time series of cloud properties of up to two overlapping layers, together with uncertainties. The OCA product is derived using the 15 min Spinning Enhanced Visible and Infrared Imager (SEVIRI) measurements onboard Meteosat Second Generation (MSG) in geostationary orbit and covers the period from 19 January 2004 until 31 August 2019. This paper presents the validation of the OCA cloud-top pressure (CTP) against independent lidar-based estimates and the quality assessment of the cloud optical thickness (COT) and cloud particle effective radius (CRE) against a combination of products from satellite-based active and passive instruments. The OCA CTP is in good agreement with the CTP sensed by lidar for low thick liquid clouds and substantially below in the case of high ice clouds, in agreement with previous studies. The retrievals of COT and CRE are more reliable when constrained by solar channels and are consistent with other retrievals from passive imagers. The resulting cloud properties are stable and homogeneous over the whole period when compared against similar CDRs from passive instruments. For CTP, the OCA CDR and the near-real-time OCA products are consistent, allowing for the use of OCA near-real time products to extend the CDR beyond August 2019. [ABSTRACT FROM AUTHOR]

Background: Cartilage transplantation is commonly used to treat large (>4 cm2) articular cartilage defects of the knee. The 2 most common transplants are osteochondral allograft transplantation and autologous chondrocyte implantation. Several patient-reported outcome measures (PROMs) have been used to determine the efficacy of treatment, but it is unknown which measures are the most effective. Purpose: To report the multiple PROMs used after large knee articular cartilage transplantation surgery and to compare the responsiveness between them. Study Design: Meta-analysis; Level of evidence, 4. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search of the PubMed/MEDLINE and Web of Science databases was performed. A total of 181 articles met inclusion criteria. Patient and study characteristics were extracted, including pre- and postoperative means for PROMs. From the articles that met inclusion criteria for responsiveness analysis (2+ PROMs reported, 1-year minimum follow-up, reported pre- and postoperative means and standard deviations; n = 131), the authors compared the responsiveness between PROM instruments using effect size and relative efficiency (RE) if a PROM could be compared with another in ≥10 articles. Results: A total of 10,015 patients (10,093 knees; mean age, 34.8 years; mean body mass index, 26.1) were included in this study. The mean follow-up time was 58.3 months (range, 1.5-247.2 months), imaging findings were reported in 80 articles (44.2%), patient satisfaction was reported in 39 articles (21.5%), and range of motion was reported in 10 articles (5.5%). There were 58 unique PROM instruments identified, with the most used being the International Knee Documentation Committee (IKDC) score (n = 118; 65.2%), followed by Knee injury and Osteoarthritis Outcome Score (KOOS) Pain (n = 58; 32.0%), KOOS Sport and Recreation (n = 58; 32.0%), KOOS Quality of Life (n = 57; 31.5%), KOOS Activities of Daily Living (n = 57; 31.5%), and KOOS Symptoms (n = 57; 31.5%). Overall, IKDC was found to have the greatest effect size (1.68) and the best responsiveness of the other PROMs, which include KOOS Pain (RE, 1.38), KOOS Symptoms (RE, 3.06), KOOS Activities of Daily Living (RE, 1.65), KOOS Sport and Recreation (RE, 1.44), Lysholm (RE, 1.76), and Tegner (RE, 1.56). Conclusion: The IKDC is the most responsive PROM after large knee articular cartilage transplantation surgery. The IKDC score is recommended for assessing outcomes after cartilage transplantation surgery. [ABSTRACT FROM AUTHOR]

Three small Baltic economies of Estonia, Latvia and Lithuania have undergone extreme economical system change from the planned economy to the market one. The institutional infrastructure have been reorganized and all three countries joined the EU and Euro area. We aim to answer which channels of economic integration are of the largest importance for the small open European economies. We showed that all three countries could be treated as one region due to development, institutional and economic similarities. Secondly, we explore whether the trade or common currency is the main channel for the business cycle synchronization across the region of three small Baltic economies. The business cycle synchronization and trade intensity (TI) between the Baltic States and their main trading partners before and after joining the EU have been investigated as an example of an ex-post case for the small economies. We have observed a large increase in TI with the trading partners from EMU and EU countries, irrespective of the TI calculation method. The analysis of business cycle synchronization of the Baltic States with their main trading partners is captured by the correlations of the cyclical component of GDP series, using the quarterly real and de-trended GDP growth data from 1995 Q1 to 2019 Q4. The panel model has indicated an important empirical feature that the common currency strongly and significantly impacted the business cycle synchronization whilst the bilateral trade intensity between the Baltic States and their main trading partners have a significant negative effect on the business cycle synchronization when controlling for time effects. The Granger causality test confirmed that the most robust impulses to the Baltic States are coming from EU trading partners. [ABSTRACT FROM AUTHOR]

Amid the evolving global economic landscape, the BRICS nations (Brazil, Russia, India, China, and South Africa) have emerged as proponents of economic multilateralism, challenging traditional paradigms of economic governance and integration. This article explores the prospects and challenges of economic integration among the BRICS nations, with specific reference to calls for an optimum currency area (OCA). With diverse economic capacities and global aspirations, these countries face significant challenges in policy coordination and structural alignment. This comprehensive literature analysis reveals the potential for and the complexity of achieving economic integration among the BRICS, underscoring the necessity for enhanced cooperation and policy harmonisation. Achieving economic integration, including the establishment of a common currency, requires an understanding of the national and collective economic goals, disparities and challenges. Offering insights into the BRICS' role in reshaping the global economic system, this analysis contributes to the discourse on economic integration among developing and emerging economies. [ABSTRACT FROM AUTHOR]

In foldable display products, an adhesive is affected by the fatigue delamination force. F‐d curve and Gc value of dynamic and static test do not exhibit a significant difference, but microbubbles are observed in dynamic folding. In this study, the fatigue delamination of adhesive in real user scene is investigated and its measurement methodology is constructed. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI), a common complication of sepsis, might be caused by overactivated inflammation, mitochondrial damage, and oxidative stress. However, the mechanisms underlying sepsis-induced AKI (SAKI) have not been fully elucidated, and there is a lack of effective therapies for AKI. To this end, this study aimed to investigate whether obeticholic acid (OCA) has a renoprotective effect on SAKI and to explore its mechanism of action. Through bioinformatics analysis, our study confirmed that the mitochondria might be a critical target for the treatment of SAKI. Thus, a septic rat model was established by cecal ligation puncture (CLP) surgery. Our results showed an evoked inflammatory response via the NF-κB signaling pathway and NLRP3 inflammasome activation in septic rats, which led to mitochondrial damage and oxidative stress. OCA, an Farnesoid X Receptor (FXR) agonist, has shown anti-inflammatory effects in numerous studies. However, the effects of OCA on SAKI remain unclear. In this study, we revealed that pretreatment with OCA can inhibit the inflammatory response by reducing the synthesis of proinflammatory factors (such as IL-1β and NLRP3) via blocking NF-κB and alleviating mitochondrial damage and oxidative stress in the septic rat model. Overall, this study provides insight into the excessive inflammation-induced SAKI caused by mitochondrial damage and evidence for the potential use of OCA in SAKI treatment.

AbstractThis paper analyzes Finland and Greece’s GDP growth and debt-to-GDP ratio post-European Monetary Union (EMU) accession. Using a robust ARDL with cointegration bounds model (2002–2021), and Johansen approach for cointegration, we find a positive impact of favorable trade balance on GDP growth and a negative impact on debt-to-GDP ratio in both nations long-term. Finland’s GDP growth is negatively affected by the country to EU average inflation ratio, while Greece sees increased debt-to-GDP due to it. Greece’s elevated government spending hampers its economic growth short- and long-term, and Finland’s debt rises in the long run with higher country to EU average unemployment. [ABSTRACT FROM AUTHOR]

This article seeks to add a new element to the 5‐decade debate over the theory of Optimal Currency Area. In the euro area, the accumulation of economic imbalances caused by the loss of the automatic adjustment functions of the exchange rate have served as a structural background to limit its self‐sustaining resilience during financial shocks. To enhance the stability of Optimal Currency Area (OCA) through the revitalization of those functions, this article argues that if the euro area had adopted some form of fiscal risk‐sharing mechanisms, which could have generated a similar economic effect as if they had maintained a flexible F/X system as that which had existed in pre‐euro days, the fiscal crisis hypothetically could have been more easily overcome within a shorter period with less financial support. The result suggests that if 'Adjustment Fund for Foreign Exchange rate Loss (AFFEL)', originally devised within these pages, had operated, the interest rates in crisis‐hit members could have been significantly lower than actual levels during the crisis, while safely maintaining the euro system. [ABSTRACT FROM AUTHOR]

Summary: Background: Low phospholipid‐associated cholelithiasis (LPAC) syndrome is a rare genetic cause of hepatolithiasis. A pathogenic variant of the ABCB4 gene is reported in half of all patients. Ursodeoxycholic acid (UDCA) is the only drug approved. However, in some patients, UDCA fails to prevent recurrence of symptoms and complications. Experimental evidence suggests that agonists of the farnesoid‐X receptor (FXR), the main transcription factor regulating ABCB4, may be beneficial in this context. Aim: To study the efficacy of obeticholic acid (OCA) in patients with LPAC syndrome with an inadequate response or intolerance to UDCA. Methods: This was a retrospective study of patients with LPAC syndrome treated with OCA, a selective FXR agonist. Results: We reviewed the records of five OCA‐treated patients (4 women; median age 29; ABCB4 variant in 4; no hepatic fibrosis). All patients received OCA at an initial dose of 5 mg daily and then 10 mg daily for a median period of 36 months in combination with UDCA (4 patients) or as a monotherapy (one patient). There were no adverse effects reported. Four patients had improvement in their symptoms ‐ three completely and one partially. One patient had no clinical benefit. Abnormalities of blood liver tests persisted in one patient despite resolution of symptoms. Radiological signs of hepatolithiasis persisted in three of the four patients who responded clinically to OCA. Conclusions: These preliminary observations suggest that OCA may have the potential to effectively treat LPAC syndrome in patients with inadequate response or intolerance to UDCA. Larger studies are needed to confirm these data. [ABSTRACT FROM AUTHOR]

Background and Aims: We have previously shown in a model of hepatic ischaemia/reperfusion injury that the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) restores reversion‐inducing‐cysteine‐rich protein with Kazal motifs (RECK), an inverse modulator of metalloproteases (MMPs) and inhibitor of the sheddases ADAM10 and ADAM17 involved in inflammation and fibrogenesis. Here, the effects of FXR agonists OCA and INT‐787 on hepatic levels of RECK, MMPs, ADAM10 and ADAM17 were compared in a diet‐induced ob/ob mouse model of non‐alcoholic steatohepatitis (NASH). Methods: Lep ob/ob NASH mice fed a high‐fat diet (HFD) or control diet (CD) for 9 weeks (wks) were treated with OCA or INT‐787 0.05% dosed via HFD admixture (30 mg/kg/day) or HFD for further 12 wks. Serum alanine transaminase (ALT) and inflammatory cytokines, liver RECK, MMP‐2 and MMP‐9 activity as well as ADAM10, ADAM17, collagen deposition (Sirius red), hepatic stellate cell activation (α‐SMA) and pCK+ reactive biliary cells were quantified. Results: Only INT‐787 significantly reduced serum ALT, IL‐1β and TGF‐β. A downregulation of RECK expression and protein levels observed in HFD groups (at 9 and 21 wks) was counteracted by both OCA and INT‐787. HFD induced a significant increase in liver MMP‐2 and MMP‐9; OCA administration reduced both MMP‐2 and MMP‐9 while INT‐787 markedly reduced MMP‐2 expression. OCA and INT‐787 reduced both ADAM10 and ADAM17 expression and number of pCK+ cells. INT‐787 was superior to OCA in decreasing collagen deposition and α‐SMA levels. Conclusion: INT‐787 is superior to OCA in controlling specific cell types and clinically relevant anti‐inflammatory and antifibrotic molecular mechanisms in NASH. [ABSTRACT FROM AUTHOR]

Background & Aims: Intestine-restricted inhibitors of the apical sodium-dependent bile acid transporter (ASBT, or ileal bile acid transporter) are approved as treatment for several inheritable forms of cholestasis but are also associated with abdominal complaints and diarrhoea. Furthermore, blocking ASBT as a single therapeutic approach may be less effective in moderate to severe cholestasis. We hypothesised that interventions that lower hepatic bile salt synthesis in addition to intestinal bile salt uptake inhibition provide added therapeutic benefit in the treatment of cholestatic disorders. Here, we test combination therapies of intestinal ASBT inhibition together with obeticholic acid (OCA), cilofexor, and the non-tumorigenic fibroblast growth factor 15 (Fgf15)/fibroblast growth factor 19 (FGF19) analogue aldafermin in a mouse model of cholestasis. Methods: Wild-type male C57Bl6J/OlaHsd mice were fed a 0.05% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet and received daily oral gavage with 10 mg/kg OCA, 30 mg/kg cilofexor, 10 mg/kg ASBT inhibitor (Linerixibat; ASBTi), or a combination. Alternatively, wild-type male C57Bl6J/OlaHsd mice were injected with adeno-associated virus vector serotype 8 (AAV8) to express aldafermin, to repress bile salt synthesis, or to control AAV8. During a 3-week 0.05% DDC diet, mice received daily oral gavage with 10 mg/kg ASBTi or placebo control. Results: Combination therapy of OCA, cilofexor, or aldafermin with ASBTi effectively reduced faecal bile salt excretion. Compared with ASBTi monotherapy, aldafermin + ASBTi further lowered plasma bile salt levels. Cilofexor + ASBTi and aldafermin + ASBTi treatment reduced plasma alanine transaminase and aspartate transaminase levels and fibrotic liver immunohistochemistry stainings. The reduction in inflammation and fibrogenesis in mice treated with cilofexor + ASBTi or aldafermin + ASBTi was confirmed by gene expression analysis. Conclusions: Combining pharmacological intestinal bile salt uptake inhibition with repression of bile salt synthesis may form an effective treatment strategy to reduce liver injury while dampening the ASBTi-induced colonic bile salt load. Impact and Implications: Combined treatment of intestinal ASBT inhibition with repression of bile salt synthesis by farnesoid X receptor agonism (using either obeticholic acid or cilofexor) or by expression of aldafermin ameliorates liver damage in cholestatic mice. In addition, compared with ASBT inhibitor monotherapy, combination treatments lower colonic bile salt load.

En las décadas que siguieron a la creación de la diócesis de Burgos hacia 1068, el flanco centro-oriental de la circunscripción, con una compleja historia geopolítica a caballo entre Castilla y Navarra, apenas figuraba en la documentación conservada en el archivo catedralicio. Todo apunta a que la actividad episcopal se circunscribía al entorno de la ciudad de Burgos. No obstante, a partir de 1160, se aprecia un renovado interés en el espacio periférico, primero en la reactivación de la antigua sede aukense y después, entre aproximadamente 1215-1235, en el espacio limítrofe con la vecina diócesis de Calahorra. La abadía de Froncea sería clave en el proceso, su cartulario el mejor testimonio de ello, y sus abades figuras claves en la imposición de la autoridad episcopal en estas tierras antaño olvidadas.

Obeticholic acid (OCA) is a first-in-class farnesoid X receptor agonist and antifibrotic agent in development for the treatment of pre-cirrhotic liver fibrosis due to non-alcoholic steatohepatitis (NASH). We aimed to validate the original 18-month liver biopsy analysis from the phase III REGENERATE trial of OCA for the treatment of NASH with a consensus panel analysis, provide additional histology data in a larger population, and evaluate safety from >8,000 total patient-years' exposure with nearly 1,000 participants receiving study drug for >4 years. Digitized whole-slide images were evaluated independently by panels of three pathologists using the NASH Clinical Research Network scoring system. Primary endpoints were (1) ≥1 stage improvement in fibrosis with no worsening of NASH or (2) NASH resolution with no worsening of fibrosis. Safety was assessed by laboratory values and adverse events. Prespecified efficacy analyses included 931 participants. The proportion of participants achieving a ≥1 stage improvement in fibrosis with no worsening of NASH was 22.4% for OCA 25 mg vs. 9.6% for placebo (p <0.0001). More participants receiving OCA 25 mg vs. placebo achieved NASH resolution with no worsening of fibrosis (6.5% vs. 3.5%, respectively; p = 0.093). Histology data in a larger population of 1,607 participants supported these results. Safety data included 2,477 participants. The incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and deaths was not substantively different across treatment groups. Pruritus was the most common TEAE. Rates of adjudicated hepatic, renal, and cardiovascular events were low and similar across treatment groups. These results confirm the antifibrotic effect of OCA 25 mg. OCA was generally well tolerated over long-term dosing. These data support a positive benefit:risk profile in patients with pre-cirrhotic liver fibrosis due to NASH. Patients with non-alcoholic steatohepatitis (NASH) often have liver scarring (fibrosis), which causes an increased risk of liver-related illness and death. Preventing progression of fibrosis to cirrhosis or reversing fibrosis are the main goals of drug development for NASH. In this clinical trial of obeticholic acid (OCA) in patients with NASH (REGENERATE), we reaffirmed our previous results demonstrating that OCA was superior to placebo in improving fibrosis using a more rigorous consensus panel analysis of liver biopsies taken at month 18. We also showed that OCA treatment resulted in dose-dependent reductions of serum liver biochemistries and liver stiffness measurements compared with placebo, even in participants in whom histologic fibrosis did not change at 18 months, providing evidence that the benefit of OCA extends beyond what is captured by the ordinal NASH CRN scoring system. OCA was well tolerated with a favorable safety profile supporting a positive benefit: risk profile in patients with pre-cirrhotic liver fibrosis due to NASH. [Display omitted] • OCA was superior to placebo in improving fibrosis by ≥1 stage with no worsening of NASH. • OCA treatment resulted in dose-dependent reductions of serum ALT levels. • OCA reduced liver stiffness compared to placebo regardless of histologic response. • OCA was generally well tolerated and demonstrated a favorable safety profile. [ABSTRACT FROM AUTHOR]

Se analiza la trayectoria plenomedieval de la antigua sede episcopal de Oca, abandonada tras la invasión islámica de 711. Nos basamos en el análisis documental, principalmente en los fondos catedralicios, emilianenses y, como novedad, el inédito cartulario de Froncea. Oca nunca recuperó una función relevante en el organigrama diocesano, perjudicada por la creación de una gran diócesis castellana centrada en Burgos y por la enajenación a San Millán de la Cogolla de su antigua sede material en el monasterio de San Felices de Oca. Acabó como una pequeña e intranscendente iglesia subordinada a la abadía de Froncea.

Successful development of treatments for non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH), has been challenging. Because NASH and fibrosis lead to progression towards cirrhosis and clinical outcomes, approaches have either sought to attenuate metabolic dysregulation and cell injury, or directly target the inflammation and fibrosis that ensue. Targets for reducing the activation of inflammatory cascades include nuclear receptor agonists (e.g. resmetirom, lanifibranor, obeticholic acid), modulators of lipotoxicity (e.g. aramchol, acetyl-CoA carboxylase inhibitors) or modification of genetic variants (e.g. PNPLA3 gene silencing). Extrahepatic inflammatory signals from the circulation, adipose tissue or gut are targets of hormonal agonists (semaglutide, tirzepatide, FGF19/FGF21 analogues), microbiota or lifestyle interventions. Stress signals and hepatocyte death activate immune responses, engaging innate (macrophages, innate lymphocyte populations) and adaptive (auto-aggressive T cells) mechanisms. Therapies have also been developed to blunt immune cell activation, recruitment (chemokine receptor inhibitors), and responses (e.g. galectin-3 inhibitors, anti-platelet drugs). The disease-driving pathways of NASH converge to elicit fibrosis, which is reversible. The activation of hepatic stellate cells into matrix-producing myofibroblasts can be inhibited by antagonising soluble factors (e.g. integrins, cytokines), cellular crosstalk (e.g. with macrophages), and agonising nuclear receptor signalling. In advanced fibrosis, cell therapy with restorative macrophages or reprogrammed (CAR) T cells may accelerate repair through hepatic stellate cell deactivation or killing, or by enhancing matrix degradation. Heterogeneity of disease – either due to genetics or divergent disease drivers – is an obstacle to defining effective drugs for all patients with NASH that will be overcome incrementally. [ABSTRACT FROM AUTHOR]

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In this work, we attempt to solve the problem of achieving more consecutive degrees of freedom (DOF) in a coprime array for direction-of-arrival (DOA) estimation. Specifically, we propose a novel coprime array, which we term as optimal coprime array (OCA). OCA has attractive features in terms of achieving a large number of uniform DOF. Also, closed-form expression of the maximum uniform DOF for a specific number of sensors is available for the OCA, which is generally not found in the coprime arrays. Another advantage of the OCA is that it has less mutual coupling as a subarray of the OCA is translated. The properties of the OCA are analyzed considering two different situations. To increase the number of uniform DOF further, we extend it up to k -times and prove that the proposed k -times extended OCA ( k -OCA) works better than the existing k -times extended coprime array in both attaining more consecutive DOF and reducing the mutual coupling effect. The k -OCA achieves the maximum number of uniform DOF for a specified number of elements among all the existing coprime arrays. The simulation results show the effectiveness of the proposed OCA and the k -OCA. [ABSTRACT FROM AUTHOR]

Since 2019, more than 20 foldable products have been released, and the categories released increased year by year. It can be seen that foldable products are increasingly favored by consumers and mobile phone manufacturers due to their advantages in expandable display size. It is expected that there will be explosive growth in the future. However, there are still some technical challenges for foldable product, such as waviness, poor impact/press resistance, and low temperature folding failure. This paper focuses on the research on improving the low temperature folding reliability of AMOLED modules. The difficulties of folding, the main failures and improvement methods, and the analysis of bending force in low temperature are introduced. Finally, the reliability for 50k times at ‐30℃ of out‐folding R 5mm, in‐folding U form R 1.5mm, in‐folding water drop form R 2mm are achieved. [ABSTRACT FROM AUTHOR]

BACKGROUND & AIMS: Metabolism supports cell proliferation and growth. Surprisingly, the tumor suppressor miR-22 is induced by metabolic stimulators like bile acids. Thus, this study examines whether miR-22 could be a metabolic silencer. METHODS: The relationship between miR-22 and the expression of fibroblast growth factor 21 (FGF21) and its receptor FGFR1 was studied in cells and fatty livers obtained from patients and mouse models. We evaluated the effect of an miR-22 inhibitor alone and in combination with obeticholic acid (OCA) for the treatment of steatosis. RESULTS: The levels of miR-22 were inversely correlated with those of FGF21, FGFR1, and PGC1α in human and mouse fatty livers, suggesting that hepatic miR-22 acts as a metabolic silencer. Indeed, miR-22 reduced FGFR1 by direct targeting and decreased FGF21 by reducing the recruitment of PPARα and PGC1α to their binding motifs. In contrast, an miR-22 inhibitor increases hepatic FGF21 and FGFR1, leading to AMPK and ERK1/2 activation, which was effective in treating alcoholic steatosis in mouse models. The farnesoid x receptor-agonist OCA induced FGF21 and FGFR1, as well as their inhibitor miR-22. An miR-22 inhibitor and OCA were effective in treating diet-induced steatosis, both alone and in combination. The combined treatment was the most effective at improving insulin sensitivity, releasing glucagon-like peptide 1, and reducing hepatic triglyceride in obese mice. CONCLUSION: The simultaneous induction of miR-22, FGF21 and FGFR1 by metabolic stimulators may maintain FGF21 homeostasis and restrict ERK1/2 activation. Reducing miR-22 enhances hepatic FGF21 and activates AMPK, which could be a novel approach to treat steatosis and insulin resistance. LAY SUMMARY: This study examines the metabolic role of a tumor suppressor, miR-22, that can be induced by metabolic stimulators such as bile acids. Our novel data revealed that the metabolic silencing effect of miR-22 occurs as a result of reductions in metabolic stimulators, which likely contribute to the development of fatty liver. Consistent with this finding, an miR-22 inhibitor effectively reversed both alcohol- and diet-induced fatty liver; miR-22 inhibition is a promising therapeutic option which could be used in combination with obeticholic acid.

Background & aimsObeticholic acid (OCA), a farnesoid X receptor agonist, increases total and low-density lipoprotein cholesterol (LDL-C) in patients with non-alcoholic steatohepatitis. In the present study, we aimed to evaluate the impact of OCA therapy on lipoprotein sub-particles.MethodThis study included 196 patients (99 OCA group and 97 placebo group) who were enrolled in the FLINT trial and had samples available for lipid analysis and liver biopsies at enrollment and end-of-treatment (EOT) at 72 weeks. Very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particles were evaluated at baseline, 12 and 72 weeks after randomization, and 24 weeks following EOT.ResultsBaseline lipoprotein profiles were similar among OCA and placebo groups. OCA did not affect total VLDL particle concentrations, but OCA vs. placebo treatment was associated with decreased large VLDL particle concentration at 12 weeks (baseline-adjusted mean: 6.8 vs. 8.9 nmol/L; p = 0.002), mirrored by an increase in less atherogenic, small VLDL particle concentration (33.9 vs. 28.0 nmol/L; p = 0.02). After 12 weeks, total LDL particle concentration was higher in the OCA group than the placebo group (1,667 vs. 1,329 nmol/L; p

Sentiment analysis is a technique for determining whether data is positive, negative, or neutral using Natural Language Processing (NLP). The particular challenge in classifying huge amounts of data is that it takes a long time and requires the employment of specialist human resources. Various deep learning techniques have been employed by different researchers to train and classify different datasets with varying outcomes. However, the results are not satisfactory. To address this challenge, this paper proposes a novel Sentiment Analysis approach based on Hybrid Neural Network Techniques. The preprocessing step is first applied to the Amazon Fine Food Reviews dataset in our architecture, which includes a number of data cleaning and text normalization techniques. The word embedding technique is then used to capture the semantics of the input by clustering semantically related inputs in the embedding space on the cleaned dataset. Finally, generated features were classified using three different deep learning techniques, including Recurrent Neural Network (RNN), Convolutional Neural Network (CNN), and Hybrid CNN-RNN models, in two different ways, with each technique as follows: classification on the original feature set and classification on the reduced feature set based on Binary Coordinate Ascent (BCA) and Optimal Coordinate Ascent (OCA). The experimental results show that a hybrid CNN-RNN with the BCA and OCA algorithms outperforms state-of-the-art methods with 97.91% accuracy.

This paper examines the argument that a small open economy with goods and service markets integrated into a major currency block has decreased autonomy over its monetary policy. The idea is derived from Optimum Currency Area theory (OCA), which tries to answer the question of what economic area is supposed to share one common currency. The main cost of joining a common currency area is a loss of independent monetary policy of the economy. Independence of monetary policy can be interpreted as the ability to set interest rates autonomously of the international interest rates. The de facto independence of an economy is strongly influenced by its size and market integration as R. McKinnon famously noted. Therefore, the paper's question is: do the countries abstaining from joining the Eurozone have a truly independent monetary policy? If the independence of their monetary policy is low, then the cost of joining the Eurozone is also low. The topic is highly relevant for the examined countries as five of them are legally bound to accept Euro. Therefore, the costs of losing "not so independent" monetary policy should not be so high. We analyze the data if the European countries with sovereign currency follow the monetary policy of the Eurozone and the United States. As previous literature stated, the independent monetary policy sets the interest rates to impact the economy's internal balance. On the other hand, if the central bank uses its interest rate tool to affect the exchange rate, then the monetary policy is not so independent. The results show that the monetary authorities of the United Kingdom, Sweden, and Denmark follow the lead of the European Central Bank much more evidently than the Czech Republic, Hungary, Poland, and Romania.

Rehabilitation after knee cartilage repair or restoration can be a challenging and nuanced process. Historically, conservative rehabilitation protocols have been characterized by limited weightbearing and restricted range of motion (ROM) were created to primarily protect the repaired cartilage but did little for progression into higher level activity. Recent literature has supported accelerated protocols in a variety of cartilage procedures ranging from osteochondral allograft (OCA) Osteochondral autograft surgery (OATS) to matrix-based scaffolding procedures such as Matrix Induced Chondrocyte Implantation (MACI) or Denovo procedures. Advances in technology such as blood flow restriction (BFR) and testing equipment with progressive rehabilitation from the acute phase through the return to sport continuum have made it possible to return to a higher level of activity and performance than first thought of for these procedures. This clinical viewpoint discusses the evolution of knee cartilage rehabilitation characterized by early but progressive weightbearing and early ROM while maintaining early homeostasis in the knee, and then its progression to return to sport and performance in the higher-level athlete. [ABSTRACT FROM AUTHOR]

Andean tubers are an ancient food crop of the Inca culture, and recently, there has been interested in determining their compounds, which can be applied as ingredients in food preparations. This review aimed to analyze the actual knowledge of the chemical, structural, technological properties and applications of Andean tuber starches reported in scientific journals and propose some end-uses. Andean tuber starches showed amylose contents between 16.5–35.3%, which influenced the physicochemical and functional properties. Few studies have reported structural features such as molecular weight, gyration radius, and amylopectin chains' chain-length distribution. More studies on structural characteristics are necessary to find structure-function relationships and suggest applications of those starches obtained from underused Andean tubers. [ABSTRACT FROM AUTHOR]

Oca Oxalis tuberosa is an Andean tuber with an important concentration of polyphenols and anthocyanins in the peel and flesh of the tuber. To exploit health and antioxidant benefits from these compounds they need to be extracted from the plant. Nowadays ultrasound and enzymatic extractions have demonstrated that they can enhance biocompound recovery over short periods of time and minimal solvent use. Therefore, the aim in this investigation is optimize pH, temperature and time for ultrasound, enzymatic extraction and their combination of anthocyanins from O. tuberosa peel. This peel is rich in carbohydrates (68.29 ± 0.37%), while starch and hemicellulose are the main constituents in the cell wall. The enzyme-ultrasound combination method showed the best results for obtaining anthocyanins using the following conditions: a 5-value of pH solvent, 30 °C temperature and 30 min of time. The concentration of monomeric anthocyanins reaches up to 583.50 ± 1.87 mg Cyn-3-glu g− 1, while antioxidant activity using DPPH increases from 806.32 ± 8.33 to 823.08 ± 1.98 mg. ET g− 1 for the extract. When ABTS radical was used the activity increased from 618.83 ± 1.45 to 657.40 ± 1.76 mg. ET g− 1 and in FRAP increased from 334.30 to 360.89 µmol Eq. Trolox g− 1. Extracts with a high content of polyphenol and anthocyanin can be used in the food and pharmaceutical industries to prevent degenerative diseases. [ABSTRACT FROM AUTHOR]

Oculocutaneous albinism (OCA) is a group of rare, inherited disorders associated with reduced melanin biosynthesis. Clinical manifestations of the eight known subtypes of OCA include hypopigmented skin, eyes, and hair and ocular manifestations, such as decreased visual acuity and nystagmus. OCA affects people globally but is most prevalent in African countries. Individuals with oculocutaneous albinism lack UV protection and are prone to skin damage and skin cancers. For many African albino individuals, there are significant challenges in seeking treatment for skin cancer and preventing sun damage due to psychosocial factors and poor education. This review summarizes the current understanding of the epidemiology, genetics, and clinical manifestations of OCA. We also discuss the medical and psychosocial challenges that affect individuals with OCA and the current landscape of albinism treatment modalities. The extent of the psychosocial challenges needs to be better understood and additional educational interventions may improve quality of life for people with albinism. [ABSTRACT FROM AUTHOR]

Background & aimsNonalcoholic steatohepatitis (NASH) is a leading cause of liver transplantation, and many trials are underway to evaluate potential therapies. The farnesoid X receptor ligand obeticholic acid in the NASH treatment trial evaluated the effects of obeticholic acid vs placebo on histologic response (defined as decrease in nonalcoholic fatty liver disease activity score [NAS] by ≥2, with no worsening of fibrosis); 45% of patients had a histologic response to obeticholic acid (25 mg), and 21% had a response to placebo (P < .01). We performed a secondary analysis of data from this trial to identify clinical parameters associated with a histologic response.MethodsWe used a logistic regression model with a stepwise selection procedure to identify baseline and early on-treatment factors associated with a histologic response at 72 weeks. Baseline demographics, liver histology, medical history, concomitant medications, cardiometabolic parameters, and serum biochemistry, as well as the changes over the course of the trial (at weeks 12 and 24), were evaluated as potential predictors of a histologic response. The model was cross-validated by a jackknife method, and performance was evaluated with the area under the receiver operating characteristic curve.ResultsThe logistic regression model found that obeticholic acid treatment, baseline NAS > 5, baseline triglyceride level ≤ 154 mg/dL, baseline international normalized ratio ≤ 1, baseline aspartate aminotransferase level ≤ 49 U/L, and a decrease in alanine aminotransferase level at week 24 by 17 U/L or more, to be significantly associated with histologic response (area under the receiver operating characteristic curve, 0.83; 95% confidence interval, 0.77-0.89; P < .0001).ConclusionsIn a secondary analysis of data from a clinical trial of obeticholic acid in patients with NASH, we identified routine clinical and laboratory parameters during the first 24 weeks of treatment (such as baseline NAS, triglyceride levels, and a decrease in alanine aminotransferase level) to significantly associate with histologic markers of response.

Background: Chondral injuries in the knee are commonly discovered during knee arthroscopy procedures. Due to the poor restoration potential and avascular nature of cartilage, large defects are commonly treated with such surgical procedures. Treatment utilizing an osteochondral allograft (OCA) transplant for symptomatic focal cartilage defects in the patellofemoral joint has demonstrated strong, lasting clinical and radiographic outcomes. Indications: Active and otherwise healthy patients are indicated for surgery when presenting with significant joint-line pain and a large focal chondral defect verified on advanced imaging after an extensive course of nonoperative management. Technique Description: Beginning with diagnostic arthroscopy to confirm the large defect of the medial femoral condyle, we proceeded with OCA transplantation. A small medial peripatellar arthrotomy is performed. The fat pad is removed for visualization and retractors are placed both medially and laterally to appropriately visualize the defect. The defect is then sized according to the appropriate sizing guide. The guide is then placed perpendicular to the defect, and a central guide pin is drilled. A scoring reamer is used to carefully cut the size of the defect followed by a central reamer to prepare the defect. Any debris is removed, and the incision is thoroughly irrigated. The defect is then carefully measured in all four quadrants to match the donor. Any underlying bone is impacted for a stable base. A drill is then used for appropriate marrow venting underneath the defect. The corresponding donor site is selected and reamed with continuous irrigation to prevent thermal necrosis. The plug is removed and carefully measured to match the recipient site. The plug is thoroughly irrigated with pulse lavage to remove marrow elements. The graft is carefully inserted with gentle manual pressure until it is seated perfectly flush with the surrounding cartilage. Results: Clinical research has demonstrated good-to-excellent long-term survivorship of OCA transplantation. Long-term return to sport rates for recreational and competitive athletes are upward of 75%. Discussion/Conclusion: As surgical techniques continue to develop, surgeons should consider utilizing OCA transplants to treat large chondral defects in the patellofemoral joint. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. [ABSTRACT FROM AUTHOR]

The discovery of nuclear receptors and transporters has contributed to the development of new drugs for the treatment of cholestatic liver diseases. Particular progress has been made in the development of second-line therapies for PBC. These new drugs can be separated into compounds primarily targeting cholestasis, molecules targeting fibrogenesis and molecules with immune-mediated action. Finally, drugs aimed at symptom relief (pruritus and fatigue) are also under investigation. Obeticholic acid is currently the only approved second-line therapy for PBC. Drugs in the late phase of clinical development include peroxisome proliferator-activated receptor agonists, norursodeoxycholic acid and NADPH oxidase 1/4 inhibitors. [ABSTRACT FROM AUTHOR]

Copyright of Espacio, Tiempo y Forma. Serie III, Historia Medieval is the property of Editorial UNED and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Compared with the traditional keyboard and mouse input method, touch screen technique has high convenience for users. With the development of technology, touch screen is widely application in various electronic products because of their high transmittance, clear images, and convenient operation. This review mainly introduces the optical clear adhesive (OCA), liquid optical clear adhesive (LOCA), and the most commonly used LOCA ultra violet (UV)‐curable adhesives. Preparation and performance of UV‐curable adhesives are deeply explored. The structure of touch screen, such as one glass solution (OGS), on‐cell and in‐cell is discussed. Moreover, lamination process includes full lamination and non‐full lamination is also discussed. This review introduces the alignment technique comprise mechanical alignment technique and non‐mechanical alignment technique (such as machine vision) and laminating equipment. The recent development and existing problems with the touch screen lamination process are discussed. Furthermore, this review describes the latest developments in the adhesive of touch screen lamination process and predicts possible future development trends, which could provide references for subsequent research work. [ABSTRACT FROM AUTHOR]

Objective: Obesity-associated nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver failure and death. However, the pathogenesis of NAFLD and its severe form, nonalcoholic steatohepatitis (NASH), is poorly understood. The energy sensor, AMP-activated protein kinase (AMPK), has decreased activity in obesity and NAFLD, but the mechanisms are unclear. Here, we examined whether obesity-induced miR-802 has a role in promoting NASH by targeting AMPK. We also investigated whether miR-802 and AMPK have roles in modulating beneficial therapeutic effects mediated by obeticholic acid (OCA), a promising clinical agent for NASH. Methods: Immunoblotting, luciferase assays, and RNA-protein interaction studies were performed to test whether miR-802 directly targets AMPK. The roles of miR-802 and AMPK in NASH were examined in mice fed a NASH-promoting diet. Results: Hepatic miR-802 and AMPK levels were inversely correlated in both NAFLD patients and obese mice. MicroRNA in silico analysis, together with biochemical studies in hepatic cells, suggested that miR-802 inhibits hepatic expression of AMPK by binding to the 3’ untranslated regions of both human AMPKα1 and mouse Ampkβ1. In diet-induced NASH mice, OCA treatment reduced hepatic miR-802 levels and improved AMPK activity, ameliorating steatosis, inflammation, and apoptosis, but these OCA-mediated beneficial effects on NASH pathologies, particularly reducing apoptosis, were reversed by overexpression of miR-802 or downregulation of AMPK. Conclusions: These results indicate that miR-802 inhibits AMPK by directly targeting Ampkβ1, promoting NAFLD/NASH in mice. The miR-802-AMPK axis that modulates OCA-mediated beneficial effects on NASH may represent a new therapeutic target.

Copyright of Chinese Journal of Liquid Crystal & Displays is the property of Chinese Journal of Liquid Crystal & Displays and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The replacement of synthetic polymers by starch biofilms entails a significant potentiality. They are non-toxic materials, biodegradable, and relatively easy to gather from several sources. However, various applications may require physicochemical properties that might prevent the use of some types of starch biofilms. Causes should be explored at the nanoscale. Here we present an atomic force microscopy surface analysis of starch biofilms extracted from the Andean tubers melloco (Ullucus tuberosus), mashua (Tropaeolum tuberosum), oca (Oxalis tuberosa), and potato (Solanum tuberosum) and relate the results to the macroscopic effects of moisture content, water activity, total soluble matter, water vapor permeability, elastic properties, opacity and IR absorption. Characterization reveals important differences at the nanoscale between the starch-based biofilms examined. Comparison permitted correlating macroscopic properties observed to the topography and tapping phase contrast segregation at the nanoscale. For instance, those samples presenting granular topography and disconnected phases at the nanoscale are associated with less elastic strength and more water molecule affinity. As an application example, we propose using the starch biofilms developed as a matrix to dispose of mouthwash and discover that melloco films are quite appropriate for this purpose. [ABSTRACT FROM AUTHOR]

Due to the versatile uses of starch, worldwide demand for it is constantly growing, compelling the exploration of new potential sources for its extraction and industrialization. In this study, the functional and microstructural properties of the starch from Oxalis tuberosa dried by oven drying (ODS), freeze-drying (FDS), and spray drying (SDS), were evaluated. Regarding the particle analysis, average sizes of 33.61 μm for ODS, 35.7 μm for SDS, and 39.16 μm for FDS were found, while the convexity of the granules was higher for SDS (0.86) and FDS (0.87) compared to ODS (0.92). The crystallinity obtained by XRD was higher in ODS (37.31%) and SDS (36.23%) compared to FDS (24.55%). The clarity of the paste was highest in FDS (80.93 ± 0.66%) followed by SDS (76.33 ± 0.3%). The swelling power was higher in SDS (16.07 ± 0.7), followed by FDS (13.16 ± 1.23) and ODS (8.59 ± 0.69). Regarding the water solubility index, FDS showed the highest solubility followed by SDS and ODS. An improvement in powder flow was noticed for SDS, followed by FDS and ODS, respectively. The results showed that the properties of O. tuberosa starch varied according to the drying method. [ABSTRACT FROM AUTHOR]

Chronic itch is a debilitating symptom profoundly impacting the quality of life in patients with liver diseases like cholestasis. Activation of the human G-protein coupled receptor, MRGPRX4 (hX4), by bile acids (BAs) is implicated in promoting cholestasis itch. However, the detailed underlying mechanisms remain elusive. Here, we identified 3-sulfated BAs that are elevated in cholestatic patients with itch symptoms. We solved the cryo-EM structure of hX4-Gq in a complex with 3-phosphated deoxycholic acid (DCA-3P), a mimic of the endogenous 3-sulfated deoxycholic acid (DCA-3S). This structure revealed an unprecedented ligand-binding pocket in MRGPR family proteins, highlighting the crucial role of the 3-hydroxyl (3-OH) group on BAs in activating hX4. Guided by this structural information, we designed and developed compound 7 (C7), a BA derivative lacking the 3-OH. Notably, C7 effectively alleviates hepatic injury and fibrosis in liver disease models while significantly mitigating the itch side effects., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Oculocutaneous albinism is an autosomal recessive disorder characterized by the presence of typical ocular features, such as foveal hypoplasia, iris translucency, hypopigmented fundus oculi and reduced pigmentation of skin and hair. Albino patients can show significant clinical variability; some individuals can present with only mild depigmentation and subtle ocular changes. Here, we provide a retrospective review of the standardized clinical charts of patients firstly addressed for evaluation of foveal hypoplasia and slightly subnormal visual acuity, whose diagnosis of albinism was achieved only after extensive phenotypic and genotypic characterization. Our report corroborates the pathogenicity of the two common TYR polymorphisms p.(Arg402Gln) and p.(Ser192Tyr) when both are located in trans with a pathogenic TYR variant and aims to expand the phenotypic spectrum of albinism in order to increase the detection rate of the albino phenotype. Our data also suggest that isolated foveal hypoplasia should be considered a clinical sign instead of a definitive diagnosis of an isolated clinical entity, and we recommend deep phenotypic and molecular characterization in such patients to achieve a proper diagnosis. [ABSTRACT FROM AUTHOR]

This paper examines the argument that a small open economy with goods and service markets integrated into a major currency block has decreased autonomy over its monetary policy. The idea is derived from Optimum Currency Area theory (OCA), which tries to answer the question of what economic area is supposed to share one common currency. The main cost of joining a common currency area is a loss of independent monetary policy of the economy. Independence of monetary policy can be interpreted as the ability to set interest rates autonomously of the international interest rates. The de facto independence of an economy is strongly influenced by its size and market integration as R. McKinnon famously noted. Therefore, the paper's question is: do the countries abstaining from joining the Eurozone have a truly independent monetary policy? If the independence of their monetary policy is low, then the cost of joining the Eurozone is also low. The topic is highly relevant for the examined countries as five of them are legally bound to accept Euro. Therefore, the costs of losing "not so independent" monetary policy should not be so high. We analyze the data if the European countries with sovereign currency follow the monetary policy of the Eurozone and the United States. As previous literature stated, the independent monetary policy sets the interest rates to impact the economy's internal balance. On the other hand, if the central bank uses its interest rate tool to affect the exchange rate, then the monetary policy is not so independent. The results show that the monetary authorities of the United Kingdom, Sweden, and Denmark follow the lead of the European Central Bank much more evidently than the Czech Republic, Hungary, Poland, and Romania. [ABSTRACT FROM AUTHOR]

In this paper, we present a new approach to contrast-agent-free angiographic visualization in optical coherence tomography (OCT). The proposed approach has much in common with imaging of local interframe strains in OCT-based elastography and utilizes the fact that the interframe motion of blood particles leads to discontinuity of strains within the vessel cross section. By this reasoning, we call this approach "elastography-inspired". Here, we first elucidate the essence and main features of the elastography-inspired approach using numerical simulation of OCT data. The simulations allow one to introduce both moving scatterers imitating blood flow in vessels as well as various masking motions imitating natural motions of living "solid" tissue surrounding the vessels. Second, using real OCT signals, we present comparative results of angiographic processing using the proposed elastography-inspired approach and a realization of OCA based on high-pass filtering of temporal variability of a series of OCT B-scans. The two methods can use the same initial dataset and the high-pass filtering OCA has already been routinely applied in both animal experiments and on patients. The new elastography-inspired method has a similar computational efficiency, and it is intrinsically able to compensate spatially-inhomogeneous masking tissue motions and demonstrates high robustness with respect to motion artefacts. Thus, the new approach looks very promising for enabling wider application of OCA in both laboratory studies on animals and, most importantly, for wider clinical applications on patients. [ABSTRACT FROM AUTHOR]

The aim of this work was to study the influence of chemical modification of Mexican Oxalis tuberosa starch by lipophilic substitution using OSA (2-octenyl-1-succinic anhydride) on its degree of substitution (DS), color, particle size (CILAS), microstructural and functional properties. The modified starches showed a dose-dependent relationship for DS with respect to the used OSA concentration (0.0167 for 2% and 0.0076 for 0.25%), as well as an increase in the % of succinic groups (from 0.983 to 2.126); high substitution efficiency is associated with the amorphous region formed by amylose, where esterification with OSA and some amylopectin branching points is suggested. An improvement in modified starch (MS1-MS5) functional properties was observed with respect to the native starch (NSO) due to the lipophilic substitution with OSA, which is generated on the molecular structure of starch. The whiteness for modified starch (MS1 to MS5) was higher (91.94–89.84%) than to native starch (87.90%). Microstructural characterization by SEM and CILAS showed starches with ovoid shape and increase in roughness (as the DS increased), the ellipse relationship trend to increasing as the DS increased (2.30–3.26), while the Feret diameter showed an inverse relationship (30.64–25.53), due to OSA chemical modifications. Modified starches of Oxalis tuberosa generated an improvement in their physicochemical, microstructural, and functional properties with respect to the native starch. These properties could be used in the food and pharmaceutical industries in gel formation, encapsulation, emulsification, films, and coatings. [ABSTRACT FROM AUTHOR]

Copyright of Geominas is the property of FUNDA-GEOMINAS. (Fundacion de Egresados d Amigos de la Escuela de Ingenieria Geologica y de Minas) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)