bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nicotinic receptor alpha5 coding polymorphism rs16969968 as a major target in disease: Functional dissection and remaining challenges
Authors: Maskos Uwe 
Published: February 2020

AbstractNicotinic acetylcholine receptors (nAChRs) are major signalling molecules in the central and peripheral nervous system. Over the last decade, they have been linked to a number of major human psychiatric and neurological conditions, like smoking, schizophrenia, Alzheimer's disease and many others. Human Genome‐Wide Association Studies (GWAS) have robustly identified genetic alterations at a locus of chromosome 15q to several of these diseases. In this review, we discuss a major coding polymorphism in the alpha5 subunit, referred to as α5SNP, and its functional dissection in vitro and in vivo. Its presence at high frequency in many human populations lends itself to pharmaceutical intervention in the context of ‘positive allosteric modulators’ (PAMs). We will present the prospects of this novel treatment, and the remaining challenges to identify suitable molecules.
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Option Profit and Loss Attribution and Pricing: A New Framework
Authors: CARR PETER , WU LIUREN 
Published: February 2020

ABSTRACTThis paper develops a new top‐down valuation framework that links the pricing of an option investment to its daily profit and loss attribution. The framework uses the Black‐Merton‐Scholes option pricing formula to attribute the short‐term option investment risk to variation in the underlying security price and the option's implied volatility. Taking risk‐neutral expectation and demanding no dynamic arbitrage result in a pricing relation that links an option's fair implied volatility level to the underlying volatility level with corrections for the implied volatility's own expected direction of movement, its variance, and its covariance with the underlying security return.
Optimal cutoff of mean corpuscular volume (MCV) for screening of alpha‐thalassemia 1 trait
Authors: Nunchai Chanhathai , Sirichotiyakul Supatra , Tongsong Theera 
Published: February 2020

AbstractAimTo identify the optimal cutoff of mean corpuscular volume (MCV) for screening of alpha‐thalassemia 1 trait.MethodsThe database of pregnant women who attended antenatal care clinic at Department of Obstetrics and Gynecology, Chiang Mai University during January 1st, 2015 to December 31st, 2017 was accessed and reviewed. A total of 1264 cases who had MCV ≤80 fL and met the inclusion criteria were enrolled to the study. Cases with hemoglobin level ≤10.0 gm/dL, iron deficiency anemia, chronic medical diseases and other types of thalassemia trait except alpha‐thalassemia 1 trait were excluded.ResultsAfter exclusion, 438 cases were available for analysis. Of them, 139 were alpha‐thalassemia 1 trait. Based on the receiver operating characteristic curves, the best cutoff value of MCV for screening of alpha‐thalassemia 1 trait was ≤76.15 fL, giving 100% sensitivity, and 60.9% specificity with the area under curve of 0.925. Compared to the conventional cutoff (≤80 fL), the new cutoff gave much less false positive tests (117 vs 299 cases), whereas capability to detect alpha‐thalassemia 1 trait was the same.ConclusionWith the new MCV cutoff (≤76.15 fL) as a secondary cutoff for screening alpha‐thalassemia 1 carrier, a substantial number of positive cases requiring DNA analysis could be avoided without compromising the detection efficacy.
Future time perspective and affect in daily life across adulthood and old age: Findings from two micro‐longitudinal studies
Authors: Katana Marko , Hill Patrick L. , Allemand Mathias 
Published: February 2020

AbstractObjectiveFuture time perspective (FTP) refers to individuals’ perceptions of the future as either open‐ended or limited. Despite well‐documented individual differences in FTP across the adult life span, little is known about short‐term variations of FTP within individuals and the within‐person associations between FTP and affective experiences.MethodStudy 1 used data from a daily diary study over 10 days (N = 564) with a wide age range across the adult life span (M = 48.30). Study 2 used data from an ambulatory assessment study over 10 days (N = 136) obtained from healthy older adults (M = 70.45).ResultsFindings suggest that 10% to 20% of the total variance in FTP was within‐person and 29% to 62% of the total variance in affect was within‐person. Multilevel modeling showed that occasions with a more open‐ended FTP were occasions with more positive affect, energetic arousal, calmness, and positive valence, and less negative affect. Age moderated the within‐person associations between FTP and positive and negative affect as well as energetic arousal, with weaker associations for older adults.ConclusionsThis research demonstrates the importance of looking at both within‐person and between‐person differences with respect to the associations between FTP and affective experiences in daily life.
Current management of non‐alcoholic steatohepatitis
Authors: Muthiah Mark D. , Sanyal Arun J. 
Published: February 2020

AbstractNon‐alcoholic steatohepatitis (NASH) is the most common cause of liver disease in Western populations, and its prevalence is increasing rapidly. It is part of a multisystem disease affecting other organs such as the kidneys, heart and blood vessels, and is closely associated with the components of the metabolic syndrome. Physicians managing patients with NASH should not only focus on the management of NASH, but also on associated comorbidities in individual patients. The approaches to treatment of NASH include either limiting energy surplus alone, or in combination with targeting of downstream pathways of inflammation and fibrosis. In this mini‐review, we discuss the currently available treatment options for NASH, as well as those in late‐stage clinical trials. We discuss the challenges of managing these patients with a limited number of approved therapies, as well as managing advanced‐stage patients with NASH and cirrhosis. We also discuss the specific management of comorbidities in NASH patients, in particular diabetes, hypertension, dyslipidaemia and cardiovascular diseases. Finally, we present the screening protocols for both hepatocellular carcinoma and extrahepatic malignancies in these patients.
The role of nutrition in non‐alcoholic fatty liver disease: Pathophysiology and management
Authors: Berná Genoveva , Romero‐Gomez Manuel 
Published: February 2020

AbstractA healthy diet together with physical activity could induce weight loss and control the progression of non‐alcoholic fatty liver disease (NAFLD). However, the composition of diet has not been clearly established. Macronutrients such as saturated fatty acids (SFA), trans‐fats, simple sugars and animal proteins have a harmful effect on the liver. On the other hand, monounsaturated fats (MUFAs), polyunsaturated (PUFAs) omega‐3‐fats, plant‐based proteins and dietary fibres are considered to be beneficial to the liver. The impact of specific micronutrients is less well‐known. Nutrients are part of the food we eat. Food makes up our meals, which compose our dietary patterns. Non‐alcoholic fatty liver disease patients usually follow Western diets which are rich in soda, frozen junk food, juice, red meat, lard, processed meats, whole fat dairy foods, fatty snack foods, take‐away foods, cakes and biscuits and poor in cereals, whole grains, fruit, vegetables, extra virgin olive oil (EVOO) and fish. On the other hand, the Mediterranean diet (MD) is beneficial for NAFLD even when it is iso‐caloric or there are no changes in body weight. A new approach, called ‘nutritional geometry’ considers the importance of integrating nutrition, animals and the environment. The goal of this approach is to combine nutrients and foods in a model to understand how food components interact to regulate the properties of diets affecting health and disease. The use of algorithms developed by artificial intelligence (AI) to create a personalized diet for patients can provide customized nutritional counselling to prevent and treat NAFLD.
Natural history of NASH and HCC
Authors: Negro Francesco 
Published: February 2020

AbstractWidespread unhealthy dietary habits associated with a sedentary lifestyle have made NAFLD the most frequent chronic liver disease worldwide, with a global prevalence of ~25%. Although NAFLD is mainly considered to be a benign disease, it can progress to severe liver fibrosis and hepatocellular carcinoma (HCC), with the latter found in non‐cirrhotic livers in about 40% of cases. Factors favouring the progression of liver disease in NAFLD are only partially understood. Male sex, older age and Caucasian ethnicity have frequently been identified as factors accelerating the progression of fibrosis in NAFLD, although data are not consistent. Host genetic variants appear to be very important, especially in the gene coding for the patatin‐like phospholipase domain‐containing 3 (PNPLA3), and they may also play a role in the development of HCC, independent of activity and the extent of liver damage. However, the most important factors affecting disease progression are found in the metabolic syndrome, that is, obesity, type 2 diabetes and arterial hypertension. This mini‐review will discuss the contribution of these factors to NAFLD‐associated morbidity, emphasizing the importance of preventive measures such as physical activity and weight control in view of the current pandemic of the metabolic syndrome.
Can we cure hepatitis B virus with novel direct‐acting antivirals?
Authors: Martinez Maria G. , Villeret François , Testoni Barbara , Zoulim Fabien 
Published: February 2020

AbstractCurrent treatments against chronic hepatitis B (CHB) include pegylated interferon alpha (Peg‐IFNα) and nucleos(t)ide analogs (NAs), the latter targeting the viral retrotranscriptase, thus inhibiting de novo viral production. Although these therapies control infection and improve the patient's quality of life, they do not cure HBV‐infected hepatocytes. A complete HBV cure is currently not possible because of the presence of the stable DNA intermediate covalently closed circular DNA (cccDNA). Current efforts are focused on achieving a functional cure, defined by the loss of Hepatitis B surface antigen (HBsAg) and undetectable HBV DNA levels in serum, and on exploring novel targets and molecules that are in the pipeline for early clinical trials. The likelihood of achieving a long‐lasting functional cure, with no rebound after therapy cessation, is higher using combination therapies targeting different steps in the hepatitis B virus (HBV) replication cycle. Novel treatments and their combinations are discussed for their potential to cure HBV infection, as well as exciting new technologies that could directly target cccDNA and cure without killing the infected cells.
Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues
Authors: Buti Maria , Roade Luisa , Riveiro‐Barciela Mar , Esteban Rafael 
Published: February 2020

AbstractManagement of chronic hepatitis B (CHB) is still considered a challenge in clinical practice. Patients must be carefully evaluated before starting therapy. This includes virology and laboratory assessments, an estimation of fibrosis by invasive and/or noninvasive methods, and an estimation of the risk of hepatocellular carcinoma (HCC). Nucleos(t)ide analogues (NAs) with a high barrier to resistance (tenofovir disoproxil fumarate [TDF], entecavir [ETV] and tenofovir alafenamide [TAF]) are the most frequently used treatments because of their good long‐term efficacy and tolerability. None of these options has been shown to be more effective than the other, but certain factors should be considered when selecting the best therapy for specific populations. Most patients achieve a virological and biochemical response to these agents, with a low rate of emerging resistance during long‐term treatment. However, the rate of hepatitis B surface antigen (HBsAg) loss is low and in most cases NAs therapy is lifelong. Safety concerns for long‐term NA use have become a priority in the management of CHB, in particular, the risk of impaired kidney function and bone marrow density loss described with TDF regimens. The risk of HCC is not completely eliminated by NAs. Thus, patients at higher risk should be identified and provided with appropriate surveillance.
Where medical education meets artificial intelligence: ‘Does technology care?’
Authors: van der Niet Anneke G. , Bleakley Alan 
Published: February 2020

Abstract‘Cold’ technologies and ‘warm’ hands‐on medicine need to walk hand‐in‐handTechnologies, such as deep learning artificial intelligence (AI), promise benign solutions to thorny, complex problems; but this view is misguided. Though AI has revolutionised aspects of technical medicine, it has brought in its wake practical, conceptual, pedagogical and ethical conundrums. For example, widespread adoption of technologies threatens to shift emphasis from ‘hands‐on’ embodied clinical work to disembodied ‘technology enhanced’ fuzzy scenarios muddying ethical responsibilities. Where AI can offer a powerful sharpening of diagnostic accuracy and treatment options, ‘cold’ technologies and ‘warm’ hands‐on medicine need to walk hand‐in‐hand. This presents a pedagogical challenge grounded in historical precedent: in the wake of Vesalian anatomy introducing the dominant metaphor of ‘body as machine,’ a medicine of qualities was devalued through the rise of instrumental scientific medicine. The AI age in medicine promises to redouble the machine metaphor, reducing complex patient experiences to linear problem‐solving interventions promising ‘solutionism.’ As an instrumental intervention, AI can objectify patients, frustrating the benefits of dialogue, as patients’ complex and often unpredictable fleshly experiences of illness are recalculated in solution‐focused computational terms.Suspicions about solutionsThe rate of change in numbers and sophistication of new technologies is daunting; they include surgical robotics, implants, computer programming and genetic interventions such as clustered regularly interspaced short palindromic repeats (CRISPR). Contributing to the focus of this issue on ‘solutionism,’ we explore how AI is often promoted as an all‐encompassing answer to complex problems, including the pedagogical, where learning ‘hands‐on’ bedside medicine has proven benefits beyond the technical. Where AI and embodied medicine have differing epistemological, ontological and axiological roots, we must not imagine that they will readily walk hand‐in‐hand down the aisle towards a happy marriage. Their union will be fractious, requiring lifelong guidance provided by a perceptive medical education suspicious of ‘smart’ solutions to complex problems.
A single amino acid substitution in the movement protein enables the mechanical transmission of a geminivirus
Authors: Lee Chia‐Hwa , Zheng You‐Xiu , Chan Chin‐Hsiang , Ku Hsin‐Mei , Chang Chung‐Jan , Jan Fuh‐Jyh 
Published: February 2020

AbstractBegomoviruses of the Geminiviridae are usually transmitted by whiteflies and rarely by mechanical inoculation. We used tomato leaf curl New Delhi virus (ToLCNDV), a bipartite begomovirus, to address this issue. Most ToLCNDV isolates are not mechanically transmissible to their natural hosts. The ToLCNDV‐OM isolate, originally identified from a diseased oriental melon plant, is mechanically transmissible, while the ToLCNDV‐CB isolate, from a diseased cucumber plant, is not. Genetic swapping and pathological tests were performed to identify the molecular determinants involved in mechanical transmission. Various viral infectious clones were constructed and successfully introduced into Nicotiana benthamiana, oriental melon, and cucumber plants by Agrobacterium‐mediated inoculation. Mechanical transmissibility was assessed via direct rub inoculation with sap prepared from infected N. benthamiana. The presence or absence of viral DNA in plants was validated by PCR, Southern blotting, and in situ hybridization. The results reveal that mechanical transmissibility is associated with the movement protein (MP) of viral DNA‐B in ToLCNDV‐OM. However, the nuclear shuttle protein of DNA‐B plays no role in mechanical transmission. Analyses of infectious clones carrying a single amino acid substitution reveal that the glutamate at amino acid position 19 of MP in ToLCNDV‐OM is critical for mechanical transmissibility. The substitution of glutamate with glycine at this position in the MP of ToLCNDV‐OM abolishes mechanical transmissibility. In contrast, the substitution of glycine with glutamate at the 19th amino acid position in the MP of ToLCNDV‐CB enables mechanical transmission. This is the first time that a specific geminiviral movement protein has been identified as a determinant of mechanical transmissibility.
Family happiness among people in a Southeast Asian city: Grounded theory study
Authors: Napa Wilai , Granger Jumpee , Kejkornkaew Siranee , Phuagsachart Pornsiri 
Published: February 2020

AbstractHappiness is a fundamental human aspiration. However, many families live in places where the cost of living is high, and there is a need for people to balance their lives to maintain happiness. This study explored the characteristics of happiness for families living in a city in Thailand. A grounded theory methodology was used to collect and analyze data. Thirteen participants were recruited into the study by purposive sampling based on a set of inclusion criteria, followed by theoretical sampling. The findings demonstrated that living together without financial problems was a core category of family happiness, which involved close connections, caring for one another and financial security. Families needed to balance these components when facing stress, using coping methods to restore happiness. To enhance family happiness, health professionals should focus on caring and communication within families, including coping techniques to maintain family happiness.
From cyanobacteria to Archaeplastida: new evolutionary insights into PII signalling in the plant kingdom
Authors: Selim Khaled A. , Ermilova Elena , Forchhammer Karl 
Published: February 2020

SummaryThe PII superfamily consists of signal transduction proteins found in all domains of life. Canonical PII proteins sense the cellular energy state through the competitive binding of ATP and ADP, and carbon/nitrogen balance through 2‐oxoglutarate binding. The ancestor of Archaeplastida inherited its PII signal transduction protein from an ancestral cyanobacterial endosymbiont. Over the course of evolution, plant PII proteins acquired a glutamine‐sensing C‐terminal extension, subsequently present in all Chloroplastida PII proteins. The PII proteins of various algal strains (red, green and nonphotosynthetic algae) have been systematically investigated with respect to their sensory and regulatory properties. Comparisons of the PII proteins from different phyla of oxygenic phototrophs (cyanobacteria, red algae, Chlorophyta and higher plants) have yielded insights into their evolutionary conservation vs adaptive properties. The highly conserved role of the controlling enzyme of arginine biosynthesis, N‐acetyl‐l‐glutamate kinase (NAGK), as a main PII‐interactor has been demonstrated across oxygenic phototrophs of cyanobacteria and Archaeplastida. In addition, the PII signalling system of red algae has been identified as an evolutionary intermediate between that of Cyanobacteria and Chloroplastida. In this review, we consider recent advances in understanding metabolic signalling by PII proteins of the plant kingdom.
Restoration of Proximal Femoral Anatomy during Total Hip Arthroplasty for High Developmental Dysplasia of the Hip: An Original Technique
Authors: Wu Kerong , Zhang Xianzuo , Chen Min , Shang Xifu 
Published: February 2020

ObjectiveTo introduce a modified osteotomy method for proximal femur reconstruction (PFR) in total hip arthroplasty (THA) for high developmental dysplasia of the hip (DDH).MethodA retrospective study was performed in a series of 24 patients (26 hips) with Crowe III/IV DDH who underwent THA and simultaneous PFR. We used an animated video to illustrate and help understand the procedure for this technique. Patients were reviewed clinically and radiographically with an average follow‐up of 31 months. The Harris hip score (HHS) was recorded preoperatively and at 3 and 12 months postoperatively.ResultsAll patients achieved primary bone union. No revision was needed up to the latest follow‐up. One patient had a dislocation due to self‐fall and received manual reduction under general anesthesia. No patient had intraoperative femoral fractures, sciatic nerve injury, or infection. The mean HHS improved from 33.48 ± 9.06 preoperatively to 84.61 ± 4.78 immediately after surgery and 90.84 ± 4.96 at 12 months.ConclusionProximal femur reconstruction is a simple and practical technique for femoral remolding during THA in patients with high DDH.
Development and Clinical Application of a New Open‐Powered Nail Anterior Cervical Plate System
Authors: Zhao Xiao‐feng , Zhao Yi‐bo , Lu Xiang‐dong , Qi De‐tai , Yang Xu , Wang Wen‐xuan , Wang Xiao‐nan , Zhou Run‐tian , Jin Yuan‐zhang , Zhao Bin 
Published: February 2020

ObjectiveTo observe and evaluate the clinical curative effect of a new type of open‐powered cervical spine system developed for anterior cervical surgery.MethodsA retrospective analysis was performed in our hospital in 2015–2017 of 329 orthopaedic patients treated with cervical anterior decompression, cage or titanium mesh graft fusion, new open‐powered nail plate or traditional cervical anterior screw plate. A total of 154 (control group) and 175 (observation group) cases were fixed with conventional cervical‐ and new open‐powered nail plates, respectively. Postoperative follow‐up was performed. Cervical stability, internal fixation position, and bone graft fusion were evaluated by imaging. Operative time, intraoperative blood loss, cervical Cobb angle, pain visual analogue scale (VAS) score, and Japanese orthopaedic association (JOA) score were compared between the groups. JOA scoring (spinal cord function) and neurological function improvement rate (IR) were used to assess clinical efficacy.ResultsThe patients were followed up for 8–36 months with an average of 19.48 months. There was no significant difference in the operation time and intraoperative blood loss between the two groups (P > 0.05). In the control group, the Cobb angles of the cervical spine were 5.13° ± 1.28°, 10.46° ± 1.07°, and 9.72° ± 1.43° before and after the operation. The observation group was followed by the Cobb angle of the cervical spine before and after the operation. They were 4.96° ± 1.39°, 11.67° ± 0.93°, and 11.13° ± 1.19°, respectively; the JOA scores before the operation, 1 week after the operation, and at the last follow‐up were (8.07 ± 1.13) points and (13.57 ± 0.82) points, and (14.19 ± 0.96) points, respectively; the IR was 86.52% ± 9.33%. The preoperative, postoperative 1 week, and last follow‐up JOA scores in the observation group were (8.37 ± 1.29) points, (14.11 ± 0.93) points, and (14.95 ± 0.78) points respectively. The IR was 88.74% ± 8.16% in the scores; the VAS scores were (5.54 ± 0.89) points, (1.73 ± 0.71) points, and (1.48 ± 0.52) points in the preoperative, postoperative 1 week, and last follow‐up in the control group. The VAS scores were (5.81 ± 0.94) points, (1.82 ± 0.61) points, and (1.16 ± 0.49) points before, 1 week, and after the final follow‐up. The JOA score and IR, VAS score and preoperative comparison between the two groups were statistically significant (P < 0.05), but there was no statistically significant difference between the two groups (P > 0.05).ConclusionThe new open‐powered nail anterior cervical plate system can achieve the same clinical effect as the traditional anterior cervical plate fixation in anterior cervical surgery, but it can simplify the operation process, effectively make up for the shortcomings of the traditional anterior cervical plate operation, and obtain satisfactory clinical application effect, which is worthy of clinical promotion.