bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dipeptidyl peptidase-4 inhibitor cardiovascular safety in patients with type 2 diabetes, with cardiovascular and renal disease: a retrospective cohort study
Authors: Baksh Sheriza , Wen Jiajun , Mansour Omar , Chang Hsien-Yen , McAdams-DeMarco Mara , Segal Jodi B. , Ehrhardt Stephan , Alexander G. Caleb 
Published: August 2021

AbstractClinical trials investigating cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) among patients with cardiovascular and renal disease rarely recruit patients with renal impairment, despite associations with increased risk for major adverse cardiovascular events (MACE). We investigated the risk of MACE associated with the use of DPP-4i among these high-risk patients. Using a new-user, retrospective, cohort design, we analyzed 2010–2015 IBM MarketScan Commercial Claims and Encounters for patients with diabetes, comorbid with cardiovascular disease and/or renal impairment. We compared time to first MACE for DPP-4i versus sulfonylurea and versus metformin. Of 113,296 individuals, 9146 (8.07%) were new DPP-4i users, 17,481 (15.43%) were new sulfonylurea users, and 88,596 (78.20%) were new metformin users. Exposure groups were not mutually exclusive. DPP-4i was associated with lower risk for MACE than sulfonylurea (aHR 0.84; 95% CI 0.74, 0.93) and similar risk for MACE to metformin (aHR 1.07; 95% CI [1.04, 1.16]). DPP-4i use was associated with lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin. This association was most evident in the first year of therapy, suggesting that DPP-4i is a safer choice than sulfonylurea for diabetes treatment initiation in high-risk patients.
Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation
Authors: Hummel Julia , Fritsche Louise , Vosseler Andreas , Dannecker Corinna , Hoene Miriam , Kantartzis Konstantinos , Häring Hans-Ulrich , Stefan Norbert , Machann Jürgen , Birkenfeld Andreas L. , Weigert Cora , Wagner Robert , Peter Andreas , Fritsche Andreas , Heni Martin 
Published: August 2021

AbstractThe selection of carbohydrates or fat to generate intracellular energy is thought to be crucial for long-term metabolic health. While most studies assess fuel selection after a metabolic challenge, the determinants of substrate oxidation in the fasted state remain largely unexplored. We therefore assessed the respiratory quotient by indirect calorimetry as a read-out for substrate oxidation following an overnight fast. This cross-sectional analysis consisted of 192 (92 women, 100 men) either lean or obese participants. Following an overnight fast, the respiratory quotient (RQ) was assessed, after which a 5-point 75-g oral glucose tolerance test was performed. Unlike glucose and insulin, fasting free fatty acids (FFA) correlated negatively with fasting RQ (p < 0.0001). Participants with high levels of the ketone body β-hydroxybutyric acid had significantly lower RQ values. Fasting levels of glucose-dependent insulinotropic polypeptide (GIP) and glicentin were positively associated with fasting RQ (allp ≤ 0.03), whereas GLP-1 showed no significant association. Neither BMI, nor total body fat, nor body fat distribution correlated with fasting RQ. No relationship between the RQ and diabetes or the metabolic syndrome could be observed. In the fasting state, FFA concentrations were strongly linked to the preferentially oxidized substrate. Our data did not indicate any relationship between fasting substrate oxidation and metabolic diseases, including obesity, diabetes, and the metabolic syndrome. Since glicentin and GIP are linked to fuel selection in the fasting state, novel therapeutic approaches that target these hormones may have the potential to modulate substrate oxidation.
Comparison between intervertebral oblique lumbar interbody fusion and transforaminal lumbar interbody fusion: a multicenter study
Authors: Takaoka Hiromitsu , Inage Kazuhide , Eguchi Yawara , Shiga Yasuhiro , Furuya Takeo , Maki Satoshi , Aoki Yasuchika , Inoue Masahiro , Fujiyoshi Takayuki , Miyamoto Takuya , Noguchi Yuji , Nakamura Shinichiro , Kinoshita Tomoaki , Kamada Takahito , Takahashi Hiroshi , Saito Junya , Norimoto Masaki , Kotani Toshiaki , Sakuma Tsuyoshi , Iijima Yasushi , Ishikawa Tetsuhiro , Umimura Tomotaka , Ohta Mitsutoshi , Suzuki-Narita Miyako , Enomoto Keigo , Sato Takashi , Sato Masashi , Suzuki Masahiro , Hozumi Takashi , Kim Geundong , Mizuki Norichika , Tsuchiya Ryuto , Otagiri Takuma , Mukaihata Tomohito , Hishiya Takahisa , Ohtori Seiji , Orita Sumihisa 
Published: August 2021

AbstractThis study aimed to perform a comparative analysis of postoperative results between lumbar degenerative spondylolisthesis (LDS) treated with oblique lateral interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) from the Chiba spine surgery registry database. Sixty-five patients who underwent single-level OLIF (O group) for LDS with ≥ 3 years’ follow-up were retrospectively reviewed. The control group comprised 78 patients who underwent single-level TLIF (T group). The analyzed variables included global alignment, radiological parameters of fused segments, asymptomatic and symptomatic ASD incidence, clinical outcomes at 3 years postoperatively using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire data, visual analogue scale scores for low back pain, lower extremity pain, and lower extremity numbness. There was no significant change in global alignment between the two groups. The rate of improvement in anterior intervertebral disc height was not significantly different between the groups at 1-month postoperatively. However, at the final evaluation, the anterior intervertebral disc height and incidence of asymptomatic ASD were significantly higher in the O group. There was no significant difference in symptomatic ASD, reoperation cases, or clinical results between groups. Thus, single-level OLIF can maintain the corrected disc height, but as it has no effect on global alignment, its benefit is limited.
Cartilage oligomeric matrix protein as a marker of progressive liver fibrosis in biliary atresia
Authors: Udomsinprasert Wanvisa , Angkathunyakul Napat , Jittikoon Jiraphun , Chaikledkaew Usa , Vejchapipat Paisarn , Poovorawan Yong , Honsawek Sittisak 
Published: August 2021

AbstractThis study aimed to determine whether mRNA and protein levels of cartilage oligomeric matrix protein (COMP), a glycoprotein responsible for modulating homeostasis of extracellular matrix, in the systemic and local liver environments were associated with clinical parameters of biliary atresia (BA) patients and might serve as a biomarker for BA severity. COMP protein levels in the circulation of 96 BA patients and 56 healthy controls and its mRNA and protein expressions in the liver of 20 BA patients and 5 non-BA patients were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry, respectively. In the circulation of BA patients, COMP levels were significantly higher than those in healthy controls. Compared with early-stage BA patients, those with advanced-stage including jaundice, fibrosis, and hepatic dysfunction had significantly increased circulating COMP levels. Raised circulating COMP levels were found to be independently correlated with degree of liver fibrosis. Survival analysis showed that elevated circulating COMP levels were significantly associated with decreased survival of BA patients. Receiver-operating characteristic curve analysis unveiled a diagnostic value of circulating COMP as a non-invasive biomarker of BA (AUC = 0.99), with a sensitivity of 100.0% and a specificity of 98.2%. In the liver, both COMP mRNA and protein expressions of BA patients with fibrosis were significantly greater than those of BA patients without fibrosis and non-BA patients. Collectively, increased circulating COMP might reflect unfavorable outcome of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.
A study of ladder-like silk foothold for the locomotion of bagworms
Authors: Yoshioka Taiyo , Yukuhiro Fumiko , Kameda Tsunenori 
Published: August 2021

AbstractWhile walking on horizontal substrates, caterpillars skilfully engage all their legs, including three pairs of thoracic legs and a maximum of five pairs of prolegs, to move in a flexible wave-like motion. Such locomotory behaviours, represented by ‘crawling’ and ‘inching’ motions, have widely inspired the development of locomotion systems in soft robotics. However, bagworms are unable to use their prolegs for walking because these are always accommodated in a portable bag; thus, they are unable to walk using such general locomotory behaviours. Indeed, how they walk with only three pairs of thoracic legs is unknown at present. In this study, we show that bagworms construct a ladder-like foothold using their silk to walk without using prolegs. This enables them to walk not only on horizontal floor surfaces but also on wall and ceiling surfaces, even those with slippery or smooth surfaces. They construct the foothold by spinning a continuous silk thread in a zigzag manner and controlling the discharge of adhesive to attach the folded parts of the silk to a substrate. Discovery of this elaborate silk utilisation technique offers fresh insights into the diversity of silk use in lepidopteran larvae and provides potential designs for robot locomotion systems.
Continuous subcutaneous insulin infusion alters microRNA expression and glycaemic variability in children with type 1 diabetes
Authors: Scott Emma S. , Januszewski Andrzej S. , Carroll Luke M. , Fulcher Gregory R. , Joglekar Mugdha V. , Hardikar Anandwardhan A. , Jones Timothy W. , Davis Elizabeth A. , Jenkins Alicia J. 
Published: August 2021

AbstractTo determine whether continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) therapy from near-diagnosis of type 1 diabetes is associated with reduced glycaemic variability (GV) and altered microRNA (miRNAs) expression. Adolescents (74% male) within 3-months of diabetes diagnosis (n = 27) were randomized to CSII (n = 12) or MDI. HbA1c, 1-5-Anhydroglucitol (1,5-AG), high sensitivity C-peptide and a custom TaqMan qPCR panel of 52 miRNAs were measured at baseline and follow-up (median (LQ-UQ); 535 (519–563) days). There were no significant differences between groups in baseline or follow-up HbA1c or C-peptide, nor baseline miRNAs. Mean ± SD 1,5-AG improved with CSII vs. MDI (3.1 ± 4.1 vs. − 2.2 ± − 7.0 mg/ml respectively, P = 0.029). On follow-up 11 miRNAs associated with diabetes vascular complications had altered expression in CSII-users. Early CSII vs. MDI use is associated with lower GV and less adverse vascular-related miRNAs. Relationships with future complications are of interest.
A genome-wide association study of quantitative computed tomographic emphysema in Korean populations
Authors: Sin Sooim , Choi Hye-Mi , Lim Jiwon , Kim Jeeyoung , Bak So Hyeon , Choi Sun Shim , Park Jinkyeong , Lee Jin Hwa , Oh Yeon-Mok , Lee Mi Kyeong , Hobbs Brian D. , Cho Michael H. , Silverman Edwin K. , Kim Woo Jin 
Published: August 2021

AbstractEmphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10–8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10–6) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10–6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.
The ABCC4 gene is associated with pyometra in golden retriever dogs
Authors: Arendt Maja , Ambrosen Aime , Fall Tove , Kierczak Marcin , Tengvall Katarina , Meadows Jennifer R. S. , Karlsson Åsa , Lagerstedt Anne-Sofie , Bergström Tomas , Andersson Göran , Lindblad-Toh Kerstin , Hagman Ragnvi 
Published: August 2021

AbstractPyometra is one of the most common diseases in female dogs, presenting as purulent inflammation and bacterial infection of the uterus. On average 20% of intact female dogs are affected before 10 years of age, a proportion that varies greatly between breeds (3–66%). The clear breed predisposition suggests that genetic risk factors are involved in disease development. To identify genetic risk factors associated with the disease, we performed a genome-wide association study (GWAS) in golden retrievers, a breed with increased risk of developing pyometra (risk ratio: 3.3). We applied a mixed model approach comparing 98 cases, and 96 healthy controls and identified an associated locus on chromosome 22 (p = 1.2 × 10–6, passing Bonferroni corrected significance). This locus contained five significantly associated SNPs positioned within introns of the ATP-binding cassette transporter 4 (ABCC4) gene. This gene encodes a transmembrane transporter that is important for prostaglandin transport. Next generation sequencing and genotyping of cases and controls subsequently identified four missense SNPs within the ABCC4 gene. One missense SNP at chr22:45,893,198 (p.Met787Val) showed complete linkage disequilibrium with the associated GWAS SNPs suggesting a potential role in disease development. Another locus on chromosome 18 overlapping the TESMIN gene, is also potentially implicated in the development of the disease.
Single cell morphology distinguishes genotype and drug effect in Hereditary Spastic Paraplegia
Authors: Wali Gautam , Berkovsky Shlomo , Whiten Daniel R. , Mackay-Sim Alan , Sue Carolyn M. 
Published: August 2021

AbstractA central need for neurodegenerative diseases is to find curative drugs for the many clinical subtypes, the causative gene for most cases being unknown. This requires the classification of disease cases at the genetic and cellular level, an understanding of disease aetiology in the subtypes and the development of phenotypic assays for high throughput screening of large compound libraries. Herein we describe a method that facilitates these requirements based on cell morphology that is being increasingly used as a readout defining cell state. In patient-derived fibroblasts we quantified 124 morphological features in 100,000 cells from 15 people with two genotypes (SPAST and SPG7) of Hereditary Spastic Paraplegia (HSP) and matched controls. Using machine learning analysis, we distinguished between each genotype and separated them from controls. Cell morphologies changed with treatment with noscapine, a tubulin-binding drug, in a genotype-dependent manner, revealing a novel effect on one of the genotypes (SPG7). These findings demonstrate a method for morphological profiling in fibroblasts, an accessible non-neural cell, to classify and distinguish between clinical subtypes of neurodegenerative diseases, for drug discovery, and potentially for biomarkers of disease severity and progression.
Towards a better understanding of the posttreatment hemodynamic behaviors in femoropopliteal arteries through personalized computational models based on OCT images
Authors: Gökgöl Can , Ueki Yasushi , Abler Daniel , Diehm Nicolas , Engelberger Rolf P. , Otsuka Tatsuhiko , Räber Lorenz , Büchler Philippe 
Published: August 2021

AbstractThe hemodynamic behavior following endovascular treatment of patients with peripheral arterial disease plays a significant role on the occurrence of restenosis in femoro-popliteal (FP) arteries. The atheroprone flow conditions that are generally accepted to promote restenosis can be calculated by computational fluid dynamics (CFD) analyses, and these results can be used to assess individualized treatment outcomes. However, the impact of endovascular therapy on the flow behaviors of FP arteries are still poorly understood, as the imaging modalities used in existing numerical works (X-ray angiography, computed tomography angiography) are unable to accurately represent the post-treatment arterial geometry due to their low resolutions. Therefore, this study proposes a new algorithm that combines intra-arterial lumen geometry obtained from high-resolution optical coherence tomography (OCT) images with centerlines generated from X-ray images to reconstruct the FP artery with an in-plane resolution of 10 µm. This superior accuracy allows modeling characteristic geometrical structures, such as angioplasty-induced arterial dissections, that are too small to be reconstructed with other imaging modalities. The framework is applied on the clinical data of patients treated either with only-percutaneous transluminal angioplasty (PTA) (n = 4) or PTA followed by stenting (n = 4). Based on the generated models, PTA was found to cause numerous arterial dissections, covering approximately 10% of the total surface area of the lumen, whereas no dissections were identified in the stented arteries. CFD simulations were performed to investigate the hemodynamic conditions before and after treatment. Regardless of the treatment method, the areas affected by low time-averaged wall shear stress (< 0.5 Pa) were significantly higher (p < 0.05) following endovascular therapy (pre-PTA: 0.95 ± 0.59 cm2; post-PTA: 2.10 ± 1.09cm2; post-stent: 3.10 ± 0.98 cm2). There were no statistical differences between the PTA and the stent groups. However, within the PTA group, adverse hemodynamics were mainly concentrated at regions created by arterial dissections, which may negatively impact the outcomes of a leave-nothing-behind strategy. These observations show that OCT-based numerical models have great potential to guide clinicians regarding the optimal treatment approach.
The Upper Triassic Polzberg palaeobiota from a marine Konservat-Lagerstätte deposited during the Carnian Pluvial Episode in Austria
Authors: Lukeneder Alexander , Lukeneder Petra 
Published: August 2021

AbstractA rich assemblage of various marine taxa from the lower Carnian Polzberg Konservat-Lagerstätte near Lunz am See (Northern Calcareous Alps, Lower Austria) is described for the first time in detail. The fossiliferous layers were deposited during the Julian 2 Ib (Austrotrachyceras austriacum Zone, Austrotrachyceras minor biohorizon). The fine-laminated Reingraben Shales comprise abundant and well-preserved members of the marine Carnian food chain. Invertebrates with the bivalve Halobia, the ammonite Austrotrachyceras and the coleoid Phragmoteuthis dominate over vertebrate actinopterygian fishes. Fragile groups such as polychaetes and isopods are entirely preserved as soft body fossils. The diverse assemblage comprises ammonites (Austrotrachyceras, Carnites, Sageceras, Simonyceras), coleoids (Phragmoteuthis, Lunzoteuthis), bivalves (Halobia), gastropods (caenogastropods/heterobranchs), one echinoid, thylacocephalan arthropods (Austriocaris), crustaceans (the decapod Platychela and isopods such as Obtusotelson, Discosalaputium), polychaetes (Palaeoaphrodite sp., eunicid polychaete), acytinopterygians (Saurichthys, Polzbergia, Peltopleurus, Habroichthys), cartilaginous fishes (Acrodus), coelacanth fish (“Coelacanthus”), a lungfish (Tellerodus), and a conodont cluster (Mosherella). Regurgitalites produced by large durophagous fish and coprolites produced by piscivorous actinopterygians accompany the Polzberg palaeobiota along with rare plant remains (Voltzia). The entire fauna of Polzberg and the excellent preservation of the specimens present a window into the Upper Triassic assemblage and palaeoenvironment during the so-called Carnian Pluvial Episode (CPE) in the early Mesozoic. The occurrence of the freshwater lungfish Tellerodus and the branchiopod Eustheria, a member of brackish to freshwater environments, points to the influence of occasional freshwater pulses or sediment transport events on the marine environment. The Polzberg palaeobiota was deposited during the global CPE, triggering the environmental conditions of the Polzberg Basin and resulting in the formation of the Reingraben Shales with the Polzberg Konservat-Lagerstätte.
Evaluation of focus and deep learning methods for automated image grading and factors influencing image quality in adaptive optics ophthalmoscopy
Authors: Sampson Danuta M. , Alonso-Caneiro David , Chew Avenell L. , La Jonathan , Roshandel Danial , Wang Yufei , Khan Jane C. , Chelva Enid , Stevenson Paul G. , Chen Fred K. 
Published: August 2021

AbstractAdaptive optics flood illumination ophthalmoscopy (AO-FIO) is an established imaging tool in the investigation of retinal diseases. However, the clinical interpretation of AO-FIO images can be challenging due to varied image quality. Therefore, image quality assessment is essential before interpretation. An image assessment tool will also assist further work on improving the image quality, either during acquisition or post processing. In this paper, we describe, validate and compare two automated image quality assessment methods; the energy of Laplacian focus operator (LAPE; not commonly used but easily implemented) and convolutional neural network (CNN; effective but more complex approach). We also evaluate the effects of subject age, axial length, refractive error, fixation stability, disease status and retinal location on AO-FIO image quality. Based on analysis of 10,250 images of 50 × 50 μm size, at 41 retinal locations, from 50 subjects we demonstrate that CNN slightly outperforms LAPE in image quality assessment. CNN achieves accuracy of 89%, whereas LAPE metric achieves 73% and 80% (for a linear regression and random forest multiclass classifier methods, respectively) compared to ground truth. Furthermore, the retinal location, age and disease are factors that can influence the likelihood of poor image quality.