bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal venular tortuosity and fractal dimension predict incident retinopathy in adults with type 2 diabetes: the Edinburgh Type 2 Diabetes Study
Authors:   on behalf of the Edinburgh Type 2 Diabetes Study (ET2DS) investigators, Forster Rachel B. , Garcia Emmanuel Sandoval , Sluiman Anniek J. , Grecian Sheila M. , McLachlan Stela , MacGillivray Tom J. , Strachan Mark W. J. , Price Jackie F. 
Published: January 2021

Abstract
Aims/hypothesis
Our aim was to determine whether a range of prespecified retinal vessel traits were associated with incident diabetic retinopathy in adults with type 2 diabetes.

Methods
In the prospective observational cohort Edinburgh Type 2 Diabetes Study of 1066 adults with type 2 diabetes, aged 60–75 years at recruitment, 718 were free from diabetic retinopathy at baseline. Baseline retinal traits including vessel widths, tortuosity (curvature) and fractal dimensions (network complexity), were quantified using fundus camera images and semiautomated software, and analysed using logistic regression for their association with incident diabetic retinopathy over 10 years.

Results
The incidence of diabetic retinopathy was 11.4% (n = 82) over 10 years. After adjustment for a range of vascular and diabetes-related risk factors, both increased venular tortuosity (OR 1.51; 95% CI 1.15, 1.98; p = 0.003) and decreased fractal dimension (OR 0.75; 95% CI 0.58, 0.96; p = 0.025) were associated with incident retinopathy. There was no evidence of an association with arterial tortuosity, and associations between measurements of vessel widths and retinopathy lost statistical significance after adjustment for diabetes-related factors and vascular disease. Adding venular tortuosity to a model including established risk factors for diabetic retinopathy (HbA1c, BP and kidney function) improved the discriminative ability (C statistic increased from 0.624 to 0.640, p = 0.013), but no such benefit was found with fractal dimension.

Conclusions/interpretation
Increased retinal venular tortuosity and decreased fractal dimension are associated with incident diabetic retinopathy, independent of classical risk factors. There is some evidence that venular tortuosity may be a useful biomarker to improve the predictive ability of models based on established retinopathy risk factors, and its inclusion in further risk prediction modelling is warranted.

Graphical abstract
Identification of potential novel drug resistance mechanisms by genomic and transcriptomic profiling of colon cancer cells with p53 deletion
Authors: Kadioglu Onat , Saeed Mohamed , Mahmoud Nuha , Azawi Shaymaa , Mrasek Kristin , Liehr Thomas , Efferth Thomas 
Published: January 2021

AbstractTP53 (p53) is a pivotal player in tumor suppression with fifty percent of all invasive tumors displaying mutations in the TP53 gene. In the present study, we characterized colon cancer cells (HCT116 p53 −/−) with TP53 deletion, a sub-line derived from HCT116-p53 +/+ cells. RNA sequencing and network analyses were performed to identify novel drug resistance mechanisms. Chromosomal aberrations were identified by multicolor fluorescence in situ hybridization (mFISH) and array comparative genomic hybridization (aCGH). Numerous genes were overexpressed in HCT116 p53 −/− cells: RND3/RhoE (235.6-fold up-regulated), DCLK1 (60.2-fold up-regulated), LBH (31.9-fold up-regulated), MYB (28.9-fold up-regulated), TACSTD2 (110.1-fold down-regulated), NRIP1 (81.5-fold down-regulated) and HLA-DMB (69.7-fold down-regulated) are among the identified genes with potential influence on multidrug resistance (MDR) and they are associated with cancer progression and tumorigenesis, according to previously published studies. Probably due to TP53 deletion, disturbances in DNA repair and apoptosis are leading to aberrancies in cellular and organismal organization, ultimately increasing tumorigenesis and cancer progression potential. With NFκB, PI3K and HSP70, being at the center of merged protein network, and TH1-2 pathways, being among the influenced pathways, it can be speculated that the inflammatory pathway contributes to a resistance phenotype together with cell cycle regulation and heat-shock response. HCT116-p53 −/− cells have more chromosomal aberrations, gains and losses in copy numbers than HCT116-p53 +/+ cells. In conclusion, numerous genomic aberrations, which might be associated with yet unknown drug resistance mechanisms, were identified. This may have important implications for future treatment strategies.
The Efficacy of Anti-Arrhythmic Drugs in Children With Idiopathic Frequent Symptomatic or Asymptomatic Premature Ventricular Complexes With or Without Asymptomatic Ventricular Tachycardia: a Retrospective Multi-Center Study
Authors: Bertels Robin A. , Kammeraad Janneke A. E. , Zeelenberg Anna M. , Filippini Luc H. , Knobbe Ingmar , Kuipers Irene M. , Blom Nico A. 
Published: January 2021

AbstractThe aim of the study is to compare the efficacy of flecainide, beta-blockers, sotalol, and verapamil in children with frequent PVCs, with or without asymptomatic VT. Frequent premature ventricular complexes (PVCs) and asymptomatic ventricular tachycardia (VT) in children with structurally normal hearts require anti-arrhythmic drug (AAD) therapy depending on the severity of symptoms or ventricular dysfunction; however, data on efficacy in children are scarce. Both symptomatic and asymptomatic children (≥ 1 year and < 18 years of age) with a PVC burden of 5% or more, with or without asymptomatic runs of VT, who had consecutive Holter recordings, were included in this retrospective multi-center study. The groups of patients receiving AAD therapy were compared to an untreated control group. A medication episode was defined as a timeframe in which the highest dosage at a fixed level of a single drug was used in a patient. A total of 35 children and 46 medication episodes were included, with an overall change in PVC burden on Holter of -4.4 percentage points, compared to -4.2 in the control group of 14 patients. The mean reduction in PVC burden was only significant in patients receiving flecainide (− 13.8 percentage points; N = 10; p = 0.032), compared to the control group and other groups receiving beta-blockers (− 1.7 percentage points; N = 18), sotalol (+ 1.0 percentage points; N = 7), or verapamil (− 3.9 percentage points; N = 11). The efficacy of anti-arrhythmic drug therapy on frequent PVCs or asymptomatic VTs in children is very limited. Only flecainide appears to be effective in lowering the PVC burden.
Frailty predicts outcome of partial nephrectomy and guides treatment decision towards active surveillance and tumor ablation
Authors: Walach M. T. , Wunderle M. F. , Haertel N. , Mühlbauer J. K. , Kowalewski K. F. , Wagener N. , Rathmann N. , Kriegmair M. C. 
Published: January 2021

Abstract
Purpose
To examine frailty and comorbidity as predictors of outcome of nephron sparing surgery (NSS) and as decision tools for identifying candidates for active surveillance (AS) or tumor ablation (TA).

Methods
Frailty and comorbidity were assessed using the modified frailty index of the Canadian Study of Health and Aging (11-CSHA) and the age-adjusted Charlson-Comorbidity Index (aaCCI) as well as albumin and the radiological skeletal-muscle-index (SMI) in a cohort of n = 447 patients with localized renal masses. Renal tumor anatomy was classified according to the RENAL nephrometry system. Regression analyses were performed to assess predictors of surgical outcome of patients undergoing NSS as well as to identify possible influencing factors of patients undergoing alternative therapies (AS/TA).

Results
Overall 409 patient underwent NSS while 38 received AS or TA. Patients undergoing TA/AS were more likely to be frail or comorbid compared to patients undergoing NSS (aaCCI: p < 0.001, 11-CSHA: p < 0.001). Gender and tumor complexity did not vary between patients of different treatment approach. 11-CSHA and aaCCI were identified as independent predictors of major postoperative complications (11-CSHA ≥ 0.27: OR = 3.6, p = 0.001) and hospital re-admission (aaCCI ≥ 6: OR = 4.93, p = 0.003) in the NSS cohort. No impact was found for albumin levels and SMI. An aaCCI > 6 and/or 11-CSHA ≥ 0.27 (OR = 9.19, p < 0.001), a solitary kidney (OR = 5.43, p = 0.005) and hypoalbuminemia (OR = 4.6, p = 0.009), but not tumor complexity, were decisive factors to undergo AS or TA rather than NSS.

Conclusion
In patients with localized renal masses, frailty and comorbidity indices can be useful to predict surgical outcome and support decision-making towards AS or TA.
Flow visualization and skin friction determination in transitional channel flow
Authors: Yimprasert Sattaya , Kvick Mathias , Alfredsson P. Henrik , Matsubara Masaharu 
Published: January 2021

Abstract
The present study experimentally determines the transitional Reynolds number range for plane channel flow and characterizes its transitional state. The pressure along the channel is measured to determine the skin friction coefficient as function of Reynolds number from the laminar state, through the transitional region into the fully turbulent state. The flow structure was studied through flow visualisation which shows that as the Reynolds number increases from the laminar state the transitional region starts showing randomly occurring turbulent spots. With increasing Reynolds number the spots shift into oblique patches and bands of small scale turbulence that form across the channel width, together with large-scale streaky structures found in areas between the turbulent regions. An image analysing technique was used to determine the intermittency factor, i.e. the turbulence fraction in the flow, as function of Reynolds number. It is found that the skin friction coefficient reaches its turbulent value before the flow is fully turbulent (the intermittency factor is still below one). This suggests that the observed streaky structures in non-turbulent regions contribute to the enhancement of the wall-normal transfer of momentum. Also above the Reynolds numbers where the turbulent skin friction coefficient has been established large-scale features consisting of irregular streaky structures are found. They have an oblique shape similar to the non-turbulent and turbulent patches in the transitional flow indicating that the transition process is not fully complete even above the Reynolds number where the skin friction reaches its turbulent level.

Graphic abstract
Fundamental flow measurement capabilities of optical Doppler and time-of-flight principles
Authors: Fischer Andreas 
Published: January 2021

AbstractIn order to understand the fundamental measurement capabilities of different flow velocity measurement principles based on Mie scattering, a fundamental equation of how to calculate the shot noise limit for a respective signal model is derived. The derivation is based on the well-known rules of uncertainty propagation and yields the Cramér–Rao bound without the necessity to calculate the Fisher information. The derived equation is next applied to compare the shot noise limit for Doppler and time-of-flight principles including laser Doppler anemometry (LDA), planar Doppler velocimetry (PDV), laser-two-focus velocimetry (L2F), particle tracking velocimetry (PTV) and particle image velocimetry (PIV). The comparison is performed for an identical mean laser power, while two cases are studied in detail: measuring on a single seeding particle as well as measuring on multiple seeding particles and averaging. LDA, L2F and PTV/PIV obey a similar shot noise limit. For the case of a measurement on multiple seeding particles, the minimal achievable measurement uncertainty is directly proportional to the absolute value of the measured velocity component and inversely proportional to the spatial resolution. The respective shot noise limit for PDV is almost independent of the measured flow velocity component and the spatial resolution. Since PDV is sensitive with respect to a different flow velocity component depending on the observation direction, a comparison with the other principles is only reasonable to a certain extent. However, all shot noise limits in case of measuring on multiple seeding particles show the expected inverse proportionality to the square root of the total number of detected photons and thus also to the square root of the measurement time. Considering a comparable spatiotemporal resolution, an identical mean light power and typical measurement configurations, the PDV shot noise limit is the largest. As a final result, it is derived that each measurement principle obeys an uncertainty principle between position and the respective component of the wave vector, which is in agreement with Heisenberg’s uncertainty principle. Therefore, a common basis is provided to assess the fundamental measurement capabilities of Doppler and time-of-flight measurement systems on the basis of what is possible within the quantum mechanical constraints.Graphic abstract
First experience with augmented reality neuronavigation in endoscopic assisted midline skull base pathologies in children
Authors: Pennacchietti Valentina , Stoelzel Katharina , Tietze Anna , Lankes Erwin , Schaumann Andreas , Uecker Florian Cornelius , Thomale Ulrich Wilhelm 
Published: January 2021

Abstract
Introduction
Endoscopic skull base approaches are broadly used in modern neurosurgery. The support of neuronavigation can help to effectively target the lesion avoiding complications. In children, endoscopic-assisted skull base surgery in combination with navigation systems becomes even more important because of the morphological variability and rare diseases affecting the sellar and parasellar regions. This paper aims to analyze our first experience on augmented reality navigation in endoscopic skull base surgery in a pediatric case series.

Patients and methods
A retrospective review identified seventeen endoscopic-assisted endonasal or transoral procedures performed in an interdisciplinary setting in a period between October 2011 and May 2020. In all the cases, the surgical target was a lesion in the sellar or parasellar region. Clinical conditions, MRI appearance, intraoperative conditions, postoperative MRI, possible complications, and outcomes were analyzed.

Results
The mean age of our patients was 14.5 ± 2.4 years. The diagnosis varied, but craniopharyngiomas (31.2%) were mostly represented. AR navigation was experienced to be very helpful for effectively targeting the lesion and defining the intraoperative extension of the pathology. In 65% of the oncologic cases, a radical removal was proven in postoperative MRI. The mean follow-up was 89 ± 79 months. There were no deaths in our series. No long-term complications were registered; two cerebrospinal fluid (CSF) fistulas and a secondary abscess required further surgery.

Conclusion
The implementation of augmented reality to endoscopic-assisted neuronavigated procedures within the skull base was feasible and did provide relevant information directly in the endoscopic field of view and was experienced to be useful in the pediatric cases, where anatomical variability and rarity of the pathologies make surgery more challenging.
Ten-year all-cause death following percutaneous or surgical revascularization in patients with prior cerebrovascular disease: insights from the SYNTAX Extended Survival study
Authors: Wang Rutao , Takahashi Kuniaki , Garg Scot , Thuijs Daniel J. F. M. , Kappetein Arie Pieter , Mack Michael J. , Morice Marie-Claude , Mohr Friedrich-Wilhelm , Curzen Nick , Davierwala Piroze , Milojevic Milan , van Geuns Robert Jan , Head Stuart J. , Onuma Yoshinobu , Holmes David R. , Serruys Patrick W. 
Published: January 2021

Abstract
Background
Coronary bypass artery grafting (CABG) has a higher procedural risk of stroke than percutaneous coronary intervention (PCI), but may offer better long-term survival. The optimal revascularization strategy for patients with prior cerebrovascular disease (CEVD) remains unclear.

Methods and results
The SYNTAXES study assessed the vital status out to 10 year of patients with three-vessel disease and/or left main coronary artery disease enrolled in the SYNTAX trial. The relative efficacy of PCI vs. CABG in terms of 10 year all-cause death was assessed according to prior CEVD. The primary endpoint was 10 year all-cause death. The status of prior CEVD was available in 1791 (99.5%) patients, of whom 253 patients had prior CEVD. Patients with prior CEVD were older and had more comorbidities (medically treated diabetes, insulin-dependent diabetes, metabolic syndrome, peripheral vascular disease, chronic obstructive pulmonary disease, impaired renal function, and congestive heart failure), compared with those without prior CEVD. Prior CEVD was an independent predictor of 10 year all-cause death (adjusted HR: 1.35; 95% CI: 1.04–1.73; p = 0.021). Patients with prior CEVD had a significantly higher risk of 10 year all-cause death (41.1 vs. 24.1%; HR: 1.92; 95% CI: 1.54–2.40; p < 0.001). The risk of 10 year all-cause death was similar between patients receiving PCI or CABG irrespective of the presence of prior CEVD (p-interaction = 0.624).

Conclusion
Prior CEVD was associated with a significantly increased risk of 10 year all-cause death which was similar in patients treated with PCI or CABG. These results do not support preferential referral for PCI rather than CABG in patients with prior CEVD.
Trial registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

Graphic abstract
Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders
Authors: Erskine Daniel , Koss David , Korolchuk Viktor I. , Outeiro Tiago F. , Attems Johannes , McKeith Ian 
Published: January 2021

AbstractAccumulation of the protein α-synuclein into insoluble intracellular deposits termed Lewy bodies (LBs) is the characteristic neuropathological feature of LB diseases, such as Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with LB (DLB). α-Synuclein aggregation is thought to be a critical pathogenic event in the aetiology of LB disease, based on genetic analyses, fundamental studies using model systems, and the observation of LB pathology in post-mortem tissue. However, some monogenic disorders not traditionally characterised as synucleinopathies, such as lysosomal storage disorders, iron storage disorders and mitochondrial diseases, appear disproportionately vulnerable to the deposition of LBs, perhaps suggesting the process of LB formation may be a result of processes perturbed as a result of these conditions. The present review discusses biological pathways common to monogenic disorders associated with LB formation, identifying catabolic processes, particularly related to lipid homeostasis, autophagy and mitochondrial function, as processes that could contribute to LB formation. These findings are discussed in the context of known mediators of α-synuclein aggregation, highlighting the potential influence of impairments to these processes in the aetiology of LB formation.
The role of serum C-reactive protein in the diagnosis of periprosthetic shoulder infection
Authors: Akgün Doruk , Wiethölter Mats , Siegert Paul , Danzinger Victor , Minkus Marvin , Braun Karl Friedrich , Moroder Philipp 
Published: January 2021

Abstract
Introduction
There is a paucity of literature regarding serum C-reactive protein (CRP) in the evaluation of a shoulder periprosthetic joint infection (PJI). The purpose of the current study was to establish cutoff values for diagnosing shoulder PJI and evaluate the influence of the type of infecting microorganism and the classification subgroups according to last proposed International Consensus Meeting (ICM) criteria on the CRP level.

Materials and methods
A retrospective analysis of all 136 patients, who underwent septic or aseptic revision shoulder arthroplasty in our institution between January 2010 and December 2019, was performed. Shoulder PJI was defined according to the last proposed definition criteria of the ICM. Serum CRP levels were compared between infected and non-infected cases, between infection subgroups, as well as between different species of infecting microorganisms. A receiver-operating characteristic (ROC) analysis was performed to display sensitivity and specificity of serum CRP level for shoulder PJI.

Results
A total of 52 patients (38%) were classified as infected, 18 meeting the criteria for definitive infection, 26 for probable infection and 8 for possible infection. According to the ROC curve, an optimized serum CRP threshold of 7.2 mg/l had a sensitivity of 69% and specificity of 74% (area under curve = 0.72). Patients with definitive infection group demonstrated significantly higher median serum CRP levels (24.3 mg/l), when compared to probable, possible infection groups and PJI unlikely group (8 mg/l, 8.3 mg/l, 3.6 mg/l, respectively, p < 0.05). The most common isolated microorganism was Cutibacterium acnes in 25 patients (48%) followed by coagulase-negative staphylococci (CNS) in 20 patients (39%). Patients with a PJI caused by high-virulent microorganisms had a significantly higher median serum CRP level compared to patients with PJI caused by low-virulent microorganisms (48 mg/l vs. 11.3 mg/l, p = 0.04).

Conclusions
Serum CRP showed a low sensitivity and specificity for the diagnosis of shoulder PJI, even applying cutoffs optimized by receiver-operating curve analysis. Low-virulent microorganisms and patients with probable and possible infections are associated with lower CRP levels compared to patients with definitive infection and infections caused by high-virulent microorganisms.

Level of evidence
Diagnostic Level III.
Development of the mouse anterior amygdalar radial unit marked by Lhx9-expression
Authors: Garcia-Calero Elena , Puelles Luis 
Published: January 2021

AbstractThe amygdala in mammals plays a key role in emotional processing and learning, being subdivided in pallial and subpallial derivatives. Recently, the cortical ring model and the pallial amygdalar radial model (Puelles et al. 2019; Garcia-Calero et al. 2020) described the pallial amygdala as an histogenetic field external to the allocortical ring, and subdivided it in five major radial domains calledlateral, basal, anterior, posterior and retroendopiriformunits. Theanteriorradial unit, whose cells typically express theLhx9gene (see molecular profile in Garcia-Calero et al. 2020), is located next to the pallial/subpallial boundary. This radial domain shows massive radial translocation and accumulation of its derivatives into its intermediate and superficial strata, with only a glial palisade representing its final periventricular domain. To better understand the development of this singular radial domain, not described previously, we followed the expression ofLhx9during mouse amygdalar development in the context of the postulated radial subdivisions of the pallial amygdala and other telencephalic developmental features.
Neural pathways of olfactory kin imprinting and kin recognition in zebrafish
Authors: Gerlach Gabriele , Wullimann Mario F. 
Published: January 2021

AbstractTeleost fish exhibit extraordinary cognitive skills that are comparable to those of mammals and birds. Kin recognition based on olfactory and visual imprinting requires neuronal circuits that were assumed to be necessarily dependent on the interaction of mammalian amygdala, hippocampus, and isocortex, the latter being a structure that teleost fish are lacking. We show that teleosts—beyond having a hippocampus and pallial amygdala homolog—also have subpallial amygdalar structures. In particular, we identify the medial amygdala and neural olfactory central circuits related to kin imprinting and kin recognition corresponding to an accessory olfactory system despite the absence of a separate vomeronasal organ.