bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hereditary Transthyretin Amyloidosis: Clinical Presentation and Management Updates
Authors: Schwartzlow Coreen , Kazamel Mohamed 
Published: February 2020

Abstract
Hereditary transthyretin amyloidosis, once a rare progressive neuropathy and/or cardiomyopathy, is now recognized with increasing worldwide frequency, various phenotypes, and over 130 gene mutations identified to date. This inherited disorder develops as a result of mutated transthyretin amyloid aggregation and systematic deposition throughout the body. With increasing knowledge about the pathophysiology of this disease, new disease-modifying therapies are being developed. In addition to slowing progression, these new agents were found to improve quality of life and reduce the severity of neuropathic symptoms. Two new gene-modifying therapies recently received Food and Drug Administration approval following the positive results from phase III trials. These include an antisense oligonucleotide, inotersen, and small interfering RNA, patisiran, which were reported to reduce the production of transthyretin and had promising safety profiles. Additional novel therapies are being explored with hopes to prolong survival. Therefore, early diagnosis of this treatable disorder has become increasingly important in clinical practice.
Possible Sampling Error in Corneal Specular Microscopy: Can Central Endothelial Data Generated by Specular Microscope Represent the Real Clinical Condition of the Whole Cornea?
Authors: van den Berg Arthur Buffara , Holzchuh Ricardo , Hida Richard Yudi 
Published: February 2020

Purpose:
To estimate the minimum number of cells required to obtain reliable data in a specular microscope, which could possibly represent the real clinical condition of the corneal endothelium.

Methods:
A cross-sectional study of 122 eyes of 61 individuals submitted to noncontact specular microscope was conducted. Data generated by the manufacturer's software were uploaded to specific statistical software for sampling relative error calculation. When relative error was above 5%, new images were acquired and more cells counted until the desired relative error was reached. Data analyzed in this study for the desired relative error were number of cells marked by the examiner for each eye (marked cells), number of cells used for data analysis (analyzed cells), endothelial area used for analysis, sampling error, and absolute number of images used for each eye.

Results:
The average number of marked cells required to obtain a relative sampling error of less than 5% was 425.2 ± 102.2 cells. The average number of analyzed cells used by the specular microscope to generate the data was 247.4 ± 51.6 cells. The average endothelial area of the analyzed cells was 0.43 ± 0.08 mm2. The mean sampling error was 3.7% ± 0.6%, and an average of 2.95 ± 0.74 images was needed to obtain a relative sampling error of less than 5%.

Conclusions:
We conclude that, theoretically, a minimum of 425.2 cells from 2.95 images must be marked to obtain reliable results, which could possibly represent the real endothelial clinical condition of the whole cornea.
Current state of adult intestinal transplantation in Europe
Authors: Clarysse Mathias , Canovai Emilio , Vanuytsel Tim , Pirenne Jacques 
Published: February 2020

Purpose of reviewIn Europe, adult intestinal transplantation (ITx) has continuously evolved since the first successful case in 1989. However, despite several recent innovations, no significant improvement in survival has been seen since 2005, illustrating the unique difficulty of transplanting the intestine. In this review, a subanalysis of adult ITx in Europe is discussed and recent publications on adult ITx in Europe are presented.Recent findingsIncreased medical and surgical arsenal in the treatment of intestinal failure reduce the need for ITx. At the same time, new indications (diffuse ischemia) have emerged. Static cold storage after vascular flush remains the gold standard but promising results are shown with additional luminal preservation. Pretransplant embolization facilitates multivisceral transplantation. Chronic rejection remains a major difficulty to tackle and currently, liver inclusion is the only effective strategy. Treatment of graft-versus-host-disease remains debated. Quality of life substantially improves after successful ITx. ITx becomes cost-effective three years after transplantation.SummaryITx remains more challenging than other solid organ transplants. However, long term outcome, particularly after combined liver and ITx, is excellent and similar to other solid organ transplants. Further studies are warranted to tackle the fundamental immunobiological challenge that ITx represents.
Material security and adherence to antiretroviral therapy among HIV-positive people who use illicit drugs
Authors: Mohd Salleh Nur Afiqah , Van Draanen Jenna , Nosova Ekaterina , Barrios Rolando , Milloy M.-.J. , Richardson Lindsey 
Published: February 2020

Objective:
To examine the relationship between poverty, operationalized using a novel material security measure, and adherence to antiretroviral therapy (ART) among people who use illicit drugs (PWUD) in a context of universal access to HIV care.

Design:
We analyzed data from a community-recruited prospective cohort in Vancouver, Canada (n = 623), from 2014 to 2017.

Methods:
We used multivariable generalized mixed-effects analyses to estimate longitudinal factors associated with mean material security score. We then estimated the association between achieving at least 95% adherence to ART and overall mean material score, as well as mean score for three factors derived from a factor analysis. The three-factor structure, employed in the current analyses, were factor 1 (basic needs); factor 2 (housing-related variables) and factor 3 (economic resources).

Results:
Recent incarceration [β-coefficient (β) = −0.176, 95% confidence interval (95% CI): −0.288 to −0.063], unmet health needs [β = −0.110, 95% CI: −0.178 to −0.042), unmet social service needs (β = −0.264, 95% CI: −0.336 to −0.193) and having access to social services (β= −0.102, 95% CI: −0.1586 to −0.0465) were among the factors associated with lower material security scores. Contrary to expectations that low levels of material security in this population would lead to poor ART adherence, we did not observe a significant relationship between adherence and overall material security score, or for each factor individually.

Conclusion:
Our findings highlight the potentially important role of no-cost, universal access to HIV prevention and treatment, in mitigating the impact of socioeconomic disadvantage on ART adherence.
Clinical Feasibility of Abbreviated Magnetic Resonance With Breath-Hold 3-Dimensional Magnetic Resonance Cholangiopancreatography for Surveillance of Pancreatic Intraductal Papillary Mucinous Neoplasm
Authors: Kang Hyo-Jin , Lee Dong Ho , Lee Jeong Min , Yoo Jeongin , Weiland Elisabeth , Kim EunJu , Son Yohan 
Published: February 2020

Objectives
To determine the clinical feasibility of abbreviated magnetic resonance image (MRI) using breath-hold 3-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) (aMRI-BH) for pancreatic intraductal papillary mucinous neoplasm (IPMN) surveillance.

Materials and Methods
In this retrospective study, 123 patients with 158 pancreatic IPMNs (pathologically proven [n = 73] and typical image feature with ≥2-year stability [n = 85]) who underwent conventional MRI (cMRI) consisting of contrast-enhanced pancreatobiliary MRI with conventional and BH-3D-MRCP were included. Two readers independently evaluated aMRI-BH protocols consisting of heavily T2-weighted, precontrast T1-weighted, and BH-3D-MRCP sequences. The diagnostic performance of aMRI-BH for detecting malignant IPMNs was assessed using the following criteria: category 3, presence of mural nodule 5 mm or bigger and/or main pancreatic duct (MPD) 10 mm or bigger; category 2, more than one of the following: cyst size 30 mm or greater, mural nodule smaller than 5 mm, thickened cyst walls, MPD of 5 to 9 mm, lymphadenopathy, and an abrupt MPD caliber change with distal atrophy; and category 1, none of the above. Categories 2 or 3 were considered positive results of surveillance. Interreader agreement of image features by intraclass correlation and κ statistics were analyzed.

Results
The total acquisition times of cMRI and aMRI-BH were 32.7 ± 8 and 5.5 ± 2.1 minutes, respectively (P < 0.01). Among 158 IPMNs, 33 lesions were malignant. The aMRI-BH presented a sensitivity of 100% and a negative predictive value of 100% for evaluating malignant IPMNs in both readers, with substantial interreader agreements (intraclass correlation or к values, range: 0.73–0.93 for cMRI and 0.57–0.94 for aMRI-BH) in significant imaging features based on revised Fukuoka guidelines, except for thickened cyst walls and lymphadenopathy (к values: 0.10 and 1.00 for cMRI and 0.13 and 0.49 for aMRI-BH, respectively).

Conclusions
The aMRI-BH provided high sensitivity and negative predictive value to evaluate malignant IPMNs by using predetermined criteria, and aMRI-BH might be a potential tool for pancreatic IPMN surveillance with significantly lower acquisition time.
Assortative mating and within-spouse pair comparisons
Authors: Howe Laurence J , Battram Thomas , Morris Tim T , Hartwig Fernando P , Hemani Gibran , Davies Neil M , Smith George Davey 
Published: February 2020

AbstractComparisons between cohabitating spouses have been proposed as an aetiological design method to reduce confounding and evaluate effects of the shared adulthood environment. However, assortative mating, a phenomenon where individuals select phenotypically similar mates, could distort associations. We evaluated the use of spousal comparisons, as in the within-spouse pair (WSP) model, for aetiological epidemiological research.Using directed acyclic graphs and simulations, we demonstrated that the WSP model can reduce confounding if spouses are correlated for an unmeasured confounder, but that WSP comparisons are susceptible to collider bias induced by assortative mating. Empirical analyses using spouse pairs in UK Biobank found evidence that genetic association estimates from the WSP model are attenuated compared to random pairs for single nucleotide polymorphisms (SNPs) associated with height (shrinkage: 23%; 95% CI 20%, 25%), educational attainment (74%; 95% CI 66%, 81%) and body mass index (23%; 95% CI 14%, 32%) as well as for an alcohol consumption SNP (29%, 95% CI 5%, 46%). Some of these attenuations are likely to reflect effects of assortative mating because height and educational attainment are unlikely to be strongly influenced by the adulthood environment. In contrast, effect estimates of increasing age on coronary artery disease and systolic blood pressure were found to be concordant between random and spouse pairs.Assortative mating is likely to induce phenotypic and genetic structure between an individual and their spouse which complicates the interpretation of spousal comparisons in an aetiological context. A further consideration is that the joint participation of non-independent spouses in cohort studies could induce selection bias.
GADL1 is a multifunctional decarboxylase with tissue-specific roles in β-alanine and carnosine production
Authors: Mahootchi Elaheh , Homaei Selina Cannon , Kleppe Rune , Winge Ingeborg , Hegvik Tor-Arne , Megias-Perez Roberto , Totland Christian , Mogavero Floriana , Baumann Anne , Glennon Jeffrey , Miletic Hrvoje , Kursula Petri , Haavik Jan 
Published: February 2020

ABSTRACTCarnosine and related β-alanine-containing peptides are believed to be important antioxidants, pH-buffers and neuromodulators. However, their biosynthetic routes and therapeutic potential are still being debated. This study describes the first animal model lacking the enzyme glutamic acid decarboxylase-like 1 (GADL1). We show that Gadl1-/-mice are deficient in β-alanine, carnosine and anserine, particularly in the olfactory bulb, cerebral cortex, and skeletal muscle. Gadl1-/-mice also exhibited decreased anxiety, increased levels of oxidative stress markers, alterations in energy and lipid metabolism, and age-related changes. Examination of the GADL1 active site indicated that the enzyme may have multiple physiological substrates, including aspartate and cysteine sulfinic acid, compatible with organ-specific functions. Human genetic studies show strong associations of the GADL1 locus with plasma levels of carnosine, subjective well-being, and muscle strength, also indicating a role for β-alanine and its peptide derivatives in these traits. Together, this shows the multifaceted and organ specific roles of carnosine peptides and establishes Gadl1 knockout mice as a versatile model to explore carnosine biology and its therapeutic potential.
Buckling of fiber metal laminated plates – numerical and experimental studies
Authors: Prasad Elluri Venkata , Sahu Shishir Kumar 
Published: February 2020

Purpose
The purpose of this study is to study the buckling behavior of new aircraft material, i.e. glass fiber metal laminated (GFML) plates.

Design/methodology/approach
The first-order Reissner–Mindlin theory is used in the present finite element formulation to determine the buckling loads of GFML plates. A program is developed in MATLAB for analyzing the effect of different parameters on buckling loads GFML plates. A set of experiments was performed to determine critical buckling loads of GFML plates using universal testing machine INSTRON 8862 and compared with predictions using the numerical model.

Findings
The effects of various parameters such as aspect ratio, side to thickness ratio, ply orientation and boundary conditions on buckling loads of GFMLs are examined. With the increase of aspect ratio, the reduction in buckling load is observed, while the increase inside to thickness ratio decreases the buckling load of GFML plates. There is a slight variation in buckling load with the increase of ply orientation. The buckling load is significantly influenced by boundary conditions because of restraint at the edges.

Practical implications
These types of materials are used in lightweight structures such as aircraft, aerospace and military vehicles. The results reported in the present study can be used as design guidelines while designing fiber metal laminated (FML) plated structures.

Originality/value
For the first time, the authors have studied the buckling behavior of bidirectional woven FML plates using both numerical and experimental techniques.
The group matters: examining the effect of group characteristics in online brand communities
Authors: Liao Junyun , Wang Lu , Huang Minxue , Yang Defeng , Wei Haiying 
Published: February 2020

PurposeIn an online brand community (OBC), consumers as a group occupy a dominant position, and their horizontal interactions are pivotal for the consumer–brand relationship. However, little is known about the effect of group characteristics on brands. To partially fill this gap, this study examines how group characteristics influence brand loyalty from the perspective of social identity theory. Specifically, by collecting data from an online survey, this paper investigates the effects of group similarity, group receptivity and group involvement on brand loyalty, the mediating role of community identification and the moderating effect of tenure in a community.Design/methodology/approachData from 482 brand community members were analyzed using structural equation modeling.FindingsThe results show that group similarity, group receptivity and group involvement increase brand loyalty; furthermore, the effect is mediated by community identification. Moreover, group receptivity is more effective in fostering community identification of short-tenure members, whereas group similarity plays a more important role for long-tenure members.Originality/valueThis paper enriches the brand community literature from a group perspective and provides implications for how brand communities develop customer loyalty strategies.
The combination of artesunate and carboplatin exerts a synergistic anti‐tumour effect on non‐small cell lung cancer
Authors: Wang Zhu , Wang Qianqian , He Tao , Li Wen , Liu Yan , Fan Yuan , Wang Yanping , Wang Qi , Chen Jie 
Published: February 2020

AbstractCarboplatin (CBP) is a widely used targeted anticancer therapeutic drug; however, multi‐drug resistance induced by the accumulation of CBP eventually causes diseases progression. The anti‐malarial drug artesunate (ART) also exerts anticancer effects in various cancers; however, the combined effect of ART and CBP on non‐small cell lung cancer (NSCLC) remains unclear. In the present study, the NSCLC cell line A549 was pretreated with various concentrations of CBP, ART and gemcitabine (GEM). 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays were conducted to detect cell viability. Cell apoptosis was evaluated by both flow cytometry and TUNEL apoptotic assay. The expression profiles of cell cycle‐related proteins and apoptotic proteins were determined by western blot. Cell clone numbers were visualized using crystal violet staining. Here, we found that both CBP and ART suppressed cell viability, and promoted cell apoptosis, and the combined application of ART and CBP at a lower concentration exhibited synergistic effects. Specifically, the combination of ART and CBP at a lower concentration suppressed cell clone numbers, promoted cell cycle arrest at the G2/M phase, and induced the expression of the cell cycle and apoptosis‐related proteins BAX, p21, p53, and Caspase‐3, while decreasing Bcl‐2 and Cyclin B1 expression. Based on these results, we concluded that combined application of ART and CBP exerts synergistic anti‐tumour effects on NSCLC by enhancing cell apoptosis in a mitochondria‐dependent manner.
Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges
Authors: Arenas‐Jal Marta , Suñé‐Negre J. M. , García‐Montoya Encarna 
Published: February 2020

AbstractWorld population growth and aging are posing unprecedented challenges in sustaining the health of 9.1 billion people that will be occupying the planet by 2050. Although noncommunicable diseases such as cardiovascular and neurodegenerative diseases, cancer, and diabetes are among the top 10 global causes of death, they can be prevented by risk factor reduction, early detection, and adequate treatment. Since a healthy diet along with dietary supplementation could play an important role to reduce morbidity and cut off its associated health care costs, research in the food and nutrition area is required to find solutions to global challenges affecting health.As a result of the healthy living trend, dietary supplements category is growing fast, leading to an urgent need for dietitians, physicians, and policy makers to broaden the scientific evidence on the efficacy and safety of a wide range of active ingredients. Coenzyme Q10 (CoQ10), as the third most consumed dietary supplement, and as a potential candidate for the treatment of various noncommunicable diseases that are among the global top 10 causes of death, has gained interest over years. Scientific evidence regarding mainly CoQ10 efficacy and safety, as well as formulation challenges, is addressed in this review.
The in vitro effect of VEGF receptor inhibition on primary alveolar osteoblast nodule formation
Authors: McLaughlin KI , Milne TJ , Zafar S , Zanicotti DG , Cullinan MP , Seymour GJ , Coates DE 
Published: February 2020

AbstractBackgroundVascular endothelial growth factor (VEGF) is a master regulator and is required for the effective coupling of angiogenesis and osteogenesis supporting both skeletal development and postnatal bone repair. A direct role for VEGF in intramembranous‐derived osteoblast growth and differentiation is not clear. We investigated the expression of primary alveolar osteoblast VEGF receptors and the subsequent effects on mineralization and nodule formation in vitro following VEGFR inhibition.MethodsPrimary human alveolar osteoblasts (HAOBs) were cultured in the presence of VEGF receptor inhibitors, exogenous VEGF or the bisphosphonate, zoledronic acid. VEGF, VEGFR1 and VEGFR2 mRNA expression and nodule formation following 21 days of culture. VEGFR1 protein expression was examined using immunofluorescence after 48 h.ResultsThe HAOBs expressed high levels of VEGF and VEGFR1 protein but VEGFR2 was not detected. The VEGFR1/2 inhibitors, ZM306416 and KRN633, lead to a dose‐dependent decrease in mineralization. Treatment with zoledronic acid showed no difference in HAOB VEGF receptor expression.ConclusionVEGF/VEGFR1 pathway appears to be important for intramembranous‐derived osteoblast differentiation and maturation in vitro.
Ceramide/sphingosine‐1‐phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma
Authors: Kim Seung‐Hyun , Jung Hae‐Won , Kim Minji , Moon Ji‐Young , Ban Ga‐Young , Kim Su Jung , Yoo Hyun‐Ju , Park Hae‐Sim 
Published: February 2020

AbstractBackgroundAsthma is associated with inflammatory dysregulation, but the underlying metabolic signatures are unclear. This study aimed to classify asthma inflammatory phenotypes based on cellular and metabolic features.MethodsTo determine cellular and metabolic profiles, we assessed inflammatory cell markers using flow cytometry, sphingolipid (SL) metabolites using LC‐MS/MS, and serum cytokines using ELISA. Targeted gene polymorphisms were determined to identify genetic predispositions related to the asthma inflammatory phenotype.ResultsIn total, 137 patients with asthma and 20 healthy controls (HCs) were enrolled. Distinct cellular and metabolic profiles were found between them; patients with asthma showed increased expressions of inflammatory cell markers and higher levels of SL metabolites compared to HCs (P < .05 for all). Cellular markers (CD66+ neutrophils, platelet‐adherent eosinophils) and SL metabolic markers (C16:0 and C24:0 ceramides) for uncontrolled asthma were also identified; higher levels were observed in uncontrolled asthma compared to controlled asthma (P < .05 for all). Asthmatics patients with higher levels of CD66+ neutrophils had lower FEV1(%), higher ACQ (but lower AQLO) scores, and higher sphingosine and C16:0 ceramide levels compared to those with low levels of CD66+ neutrophils. Asthmatics patients with higher levels of platelet‐adherent eosinophils had higher S1P levels compared to those with lower levels of platelet‐adherent eosinophils. Patients carrying TT genotype of ORMDL3 had more CD66+ neutrophils; those with AG/ GG genotypes of SGMS1 exhibited higher platelet‐adherent eosinophils.ConclusionPatients with uncontrolled asthma possess distinct inflammatory phenotypes including increased CD66+ neutrophils and platelet‐adherent eosinophils, with an imbalanced ceramide/S1P rheostat, potentially involving ORMDL3 and SGMS1 gene polymorphisms. Ceramide/S1P synthesis could be targeted to control airway inflammation.