bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermally-Induced Shape-Memory Behavior of Degradable Gelatin-Based Networks
Authors: Neffe Axel T. , Löwenberg Candy , Julich-Gruner Konstanze K. , Behl Marc , Lendlein Andreas
Published: May 2021

Shape-memory hydrogels (SMH) are multifunctional, actively-moving polymers of interest in biomedicine. In loosely crosslinked polymer networks, gelatin chains may form triple helices, which can act as temporary net points in SMH, depending on the presence of salts. Here, we show programming and initiation of the shape-memory effect of such networks based on a thermomechanical process compatible with the physiological environment. The SMH were synthesized by reaction of glycidylmethacrylated gelatin with oligo(ethylene glycol) (OEG) α,ω-dithiols of varying crosslinker length and amount. Triple helicalization of gelatin chains is shown directly by wide-angle X-ray scattering and indirectly via the mechanical behavior at different temperatures. The ability to form triple helices increased with the molar mass of the crosslinker. Hydrogels had storage moduli of 0.27–23 kPa and Young’s moduli of 215–360 kPa at 4 °C. The hydrogels were hydrolytically degradable, with full degradation to water-soluble products within one week at 37 °C and pH = 7.4. A thermally-induced shape-memory effect is demonstrated in bending as well as in compression tests, in which shape recovery with excellent shape-recovery rates Rr close to 100% were observed. In the future, the material presented here could be applied, e.g., as self-anchoring devices mechanically resembling the extracellular matrix.
The Significance of COVID-19 Immunological Status in Severe Neurological Complications and Multiple Sclerosis—A Literature Review
Authors: Kulikowska Joanna , Kulczyńska-Przybik Agnieszka , Mroczko Barbara , Kułakowska Alina
Published: May 2021

SARS-CoV-2/Coronavirus 2019 (COVID-19) is responsible for the pandemic, which started in December 2019. In addition to the typical respiratory symptoms, this virus also causes other severe complications, including neurological ones. In diagnostics, serological and polymerase chain reaction tests are useful not only in detecting past infections but can also predict the response to vaccination. It is now believed that an immune mechanism rather than direct viral neuroinvasion is responsible for neurological symptoms. For this reason, it is important to assess the presence of antibodies not only in the serum but also in the cerebrospinal fluid (CSF), especially in the case of neuro-COVID. A particular group of patients are people with multiple sclerosis (MS) whose disease-modifying drugs weaken the immune system and lead to an unpredictable serological response to SARS-CoV-2 infection. Based on available data, the article summarizes the current serological information concerning COVID-19 in CSF in patients with severe neurological complications and in those with MS.
Elevating the Levels of Calcium Ions Exacerbate Alzheimer’s Disease via Inducing the Production and Aggregation of β-Amyloid Protein and Phosphorylated Tau
Authors: Guan Pei-Pei , Cao Long-Long , Wang Pu
Published: May 2021

Alzheimer’s disease (AD) is a neurodegenerative disease with a high incidence rate. The main pathological features of AD are β-amyloid plaques (APs), which are formed by β-amyloid protein (Aβ) deposition, and neurofibrillary tangles (NFTs), which are formed by the excessive phosphorylation of the tau protein. Although a series of studies have shown that the accumulation of metal ions, including calcium ions (Ca2+), can promote the formation of APs and NFTs, there is no systematic review of the mechanisms by which Ca2+ affects the development and progression of AD. In view of this, the current review summarizes the mechanisms by which Ca2+ is transported into and out of cells and organelles, such as the cell, endoplasmic reticulum, mitochondrial and lysosomal membranes to affect the balance of intracellular Ca2+ levels. In addition, dyshomeostasis of Ca2+ plays an important role in modulating the pathogenesis of AD by influencing the production and aggregation of Aβ peptides and tau protein phosphorylation and the ways that disrupting the metabolic balance of Ca2+ can affect the learning ability and memory of people with AD. In addition, the effects of these mechanisms on the synaptic plasticity are also discussed. Finally, the molecular network through which Ca2+ regulates the pathogenesis of AD is introduced, providing a theoretical basis for improving the clinical treatment of AD.
Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential
Authors: Brandão Bruna B. , Poojari Ankita , Rabiee Atefeh
Published: May 2021

The concerning worldwide increase of obesity and chronic metabolic diseases, such as T2D, dyslipidemia, and cardiovascular disease, motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there has been growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat, as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Furthermore, we discuss the alterations in brown and beige adipose tissue function during obesity and explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.
Re-Evaluation of the Prevalence of Permanent Congenital Hypothyroidism in Niigata, Japan: A Retrospective Study
Authors: Nagasaki Keisuke , Sato Hidetoshi , Sasaki Sunao , Nyuzuki Hiromi , Shibata Nao , Sawano Kentaro , Hiroshima Shota , Asami Tadashi
Published: May 2021

Although newborn screening (NBS) for congenital hypothyroidism (CH) in Japan started more than 40 years ago, the prevalence of CH remains unclear. Prevalence estimations among NBS-positive CH individuals include those with transient hypothyroidism and transient hyperthyrotropinemia, and re-evaluation with increasing age is necessary to clarify the actual incidence. Thus, we re-evaluated the incidence of permanent CH. Of the 106,114 patients who underwent NBS in the Niigata Prefecture, Japan, between April 2002 and March 2006, 116 were examined further due to high thyroid-stimulating hormone levels (>8 mIU/L) and were included in the study. We retrospectively evaluated their levothyroxine sodium (LT4) replacement therapy status from the first visit to 15 years of age. Of the 116 NBS-positive patients, 105 (91%) were initially examined in our department. Of these, 72 (69%) started LT4 replacement therapy on the first visit. Subsequently, 27 patients continued LT4 replacement until 15 years of age after multiple re-evaluations. The prevalence of permanent CH in the Niigata Prefecture during this period was 1 in 2500–3500 children. Ultimately, 62.5% of patients on LT4 replacement discontinued treatment by 15 years of age. This is the first study to clarify the true prevalence of permanent CH in Japan.
Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report
Authors: Corre Camille S. , Matern Dietrich , Pellegrino Joan E. , Saavedra-Matiz Carlos A. , Orsini Joseph J. , Thompson-Stone Robert
Published: May 2021

Krabbe disease (KD) is a rare inherited neurodegenerative disorder caused by a deficiency in galactocerebrosidase enzyme activity, which can present in early infancy, requiring an urgent referral for hematopoietic stem cell transplantation, or later in life. Newborn screening (NBS) for KD requires identification and risk-stratification of patients based on laboratory values to predict disease onset in early infancy or later in life. The biomarker psychosine plays a key role in NBS algorithms to ascertain probability of early-onset disease. This report describes a patient who was screened positive for KD in New York State, had a likely pathogenic genotype, and showed markedly reduced enzyme activity but surprisingly low psychosine levels. The patient ultimately developed KD in late infancy, an outcome not clearly predicted by existing NBS algorithms. It remains critical that psychosine levels be evaluated alongside genotype, enzyme activity levels, and the patient’s evolving clinical presentation, ideally in consultation with experts in KD, in order to guide diagnosis and plans for monitoring.
Research on Estimation Method of Geometric Features of Structured Negative Obstacle Based on Single-Frame 3D Laser Point Cloud
Authors: Li Xingdong , Gao Zhiming , Chen Xiandong , Sun Shufa , Liu Jiuqing
Published: May 2021

A single VLP-16 LiDAR estimation method based on a single-frame 3D laser point cloud is proposed to address the problem of estimating negative obstacles’ geometrical features in structured environments. Firstly, a distance measurement method is developed to determine the estimation range of the negative obstacle, which can be used to verify the accuracy of distance estimation. Secondly, the 3D point cloud of a negative obstacle is transformed into a 2D elevation raster image, making the detection and estimation of negative obstacles more intuitive and accurate. Thirdly, we compare the effects of a StatisticalOutlierRemoval filter, RadiusOutlier removal, and Conditional removal on 3D point clouds, and the effects of a Gauss filter, Median filter, and Aver filter on 2D image denoising, and design a flowchart for point cloud and image noise reduction and denoising. Finally, a geometrical feature estimation method is proposed based on the elevation raster image. The negative obstacle image in the raster is used as an auxiliary line, and the number of pixels is derived from the OpenCV-based Progressive Probabilistic Hough Transform to estimate the geometrical features of the negative obstacle based on the raster size. The experimental results show that the algorithm has high accuracy in estimating the geometric characteristics of negative obstacles on structured roads and has a practical application value for LiDAR environment perception research.
Native and Non-Native Egg Parasitoids Associated with Brown Marmorated Stink Bug (Halyomorpha halys [Stål, 1855]; Hemiptera: Pentatomidae) in Western Slovenia
Authors: Rot Mojca , Maistrello Lara , Costi Elena , Bernardinelli Iris , Malossini Giorgio , Benvenuto Luca , Trdan Stanislav
Published: May 2021

Halyomorpha halys (Hemiptera: Pentatomidae), native to East Asia, has become a globally invasive pest, as a serious threat to agricultural production and a notorious nuisance pest in urban areas. Considerable efforts have been made so far to develop effective pest control measures to prevent crop damage. Biological control of this invasive stink bug by egg parasitoids has proven to be the most environmentally sustainable long-term solution. Knowledge of the native egg parasitoid fauna is of key importance when implementing a biological control program. Therefore, the main objective of our study was to detect egg parasitoid species associated with H. halys in the Goriška region (Western Slovenia) and to evaluate their impact on the pest population under field conditions. In the years 2019 and 2020, around 4600 H. halys eggs were collected in the wild and more than 3400 sentinel eggs were exposed to detect parasitoids in the field. Five egg-parasitoid species emerged from H. halys eggs: Anastatus bifasciatus (Hymenoptera: Eupelmidae), Telenomus sp., Trissolcus basalis, Trissolcus mitsukurii (Hymenoptera: Scelionidae) and Ooencyrtus telenomicida (Hymenoptera: Encyrtidae), all of them are new records for Slovenia. The native species, An. bifasciatus, dominated in urban and suburban areas, while non-native Tr. mitsukurii prevailed in agricultural areas. Overall parasitism rates of naturally laid eggs by the parasitoid species complex in 2019 and 2020 was 3.0 and 14.4%, respectively. Rapid recruitment of native parasitoids, early detection of an effective alien parasitoid species and increasing overall parasitism rates are very encouraging results, which need to be followed and verified in future research.
Psychometric Characteristics of the Patient-Reported Outcome Measures Applied in the CENTER-TBI Study
Authors: Steinbuechel Nicole , Rauen Katrin , Bockhop Fabian , Covic Amra , Krenz Ugne , Plass Anne , Cunitz Katrin , Polinder Suzanne , Wilson Lindsay , Steyerberg Ewout , Maas Andrew , Menon David , Wu Yi-Jhen , Zeldovich Marina , the CENTER-TBI Participants and Investigators
Published: May 2021

Traumatic brain injury (TBI) may lead to impairments in various outcome domains. Since most instruments assessing these are only available in a limited number of languages, psychometrically validated translations are important for research and clinical practice. Thus, our aim was to investigate the psychometric properties of the patient-reported outcome measures (PROM) applied in the CENTER-TBI study. The study sample comprised individuals who filled in the six-months assessments (GAD-7, PHQ-9, PCL-5, RPQ, QOLIBRI/-OS, SF-36v2/-12v2). Classical psychometric characteristics were investigated and compared with those of the original English versions. The reliability was satisfactory to excellent; the instruments were comparable to each other and to the original versions. Validity analyses demonstrated medium to high correlations with well-established measures. The original factor structure was replicated by all the translations, except for the RPQ, SF-36v2/-12v2 and some language samples for the PCL-5, most probably due to the factor structure of the original instruments. The translation of one to two items of the PHQ-9, RPQ, PCL-5, and QOLIBRI in three languages could be improved in the future to enhance scoring and application at the individual level. Researchers and clinicians now have access to reliable and valid instruments to improve outcome assessment after TBI in national and international health care.
Short- and Long-Term Impact of Smoking Donors in Lung Transplantation: Clinical and Pathological Analysis
Authors: Schiavon Marco , Lloret Madrid Andrea , Lunardi Francesca , Faccioli Eleonora , Lorenzoni Giulia , Comacchio Giovanni Maria , Rebusso Alessandro , Dell’Amore Andrea , Mammana Marco , Nicotra Samuele , Braccioni Fausto , Gregori Dario , Cozzi Emanuele , Calabrese Fiorella , Rea Federico
Published: May 2021

Background: The use of smoking donors (SD) is one strategy to increase the organ pool for lung transplantation (LT), but the benefit-to-risk ratio has not been demonstrated. This study aimed to evaluate the impact of SD history on recipient outcomes and graft alterations. Methods: LTs in 293 patients were retrospectively reviewed and divided into non-SD (n = 225, group I), SD < 20 pack-years (n = 45, group II), and SD ≥ 20 pack-years (n = 23, group III) groups. Moreover, several lung donor biopsies before implantation (equally divided between groups) were evaluated, focusing on smoking-related lesions. Correlations were analyzed between all pathological data and smoking exposure, along with other clinical parameters. Results: Among the three groups, donor and recipient characteristics were comparable, except for higher Oto scores and age in group III. Group III showed a longer intensive care unit (ICU) and hospital stay compared with the other two groups. This finding was confirmed when SD history was considered as a continuous variable. However, survival and other mid- and long-term major outcomes were not affected by smoking history. Finally, morphological lesions did not differ between the three groups. Conclusions: In our study, SDs were associated with a longer post-operative course, without affecting graft aspects or mid- and long-term outcomes. A definition of pack-years cut-off for organ refusal should be balanced with the other extended criteria donor factors.
Influence of Metabolic Syndrome on Cancer Risk in HBV Carriers: A Nationwide Population Based Study Using the National Health Insurance Service Database
Authors: Choe Jung Wan , Hyun Jong Jin , Kim Bongseong , Han Kyung-Do
Published: May 2021

Purpose: Hepatitis B virus (HBV) infection and metabolic syndrome (MS) are known independent risk factors for hepatocellular carcinoma (HCC) and other extrahepatic organ malignancies. The purpose of this study was to investigate whether MS and HBV have synergistic effects on cancers and to examine whether increasing the number of MS components could lead to higher risk of cancer development. Materials and Methods: We evaluated data from 1,504,880 HBV-infected adults who underwent a regular HCC screening program provided by the Korean National Health Insurance Service between 2009 and 2016. Results: The prevalence of MS in Korean HBV patients was 38.7% (582,449/1,504,880). Among individuals with HBV infection, the presence of MS was associated with an increased risk for the majority of malignancies except for HCC (HR = 0.862, p-value < 0.05). The presence of a higher number of MS components was associated with a significantly increased risk of developing cancers in most organs; only HCC was negatively associated with an increasing number of MS components (p < 0.01). Conclusions: Our data show that the presence of MS increases the risk for most malignancies, excluding HCC. Moreover, we found that as the number of MS components increased, the risk for most cancers also increased; this trend was reversed in HCC.
Epithelial-to-Mesenchymal Transition in the Light of Plasticity and Hybrid E/M States
Authors: Bornes Laura , Belthier Guillaume , van Rheenen Jacco
Published: May 2021

Epithelial-to-mesenchymal transition (EMT) is a cellular program which leads to cells losing epithelial features, including cell polarity, cell–cell adhesion and attachment to the basement membrane, while gaining mesenchymal characteristics, such as invasive properties and stemness. This program is involved in embryogenesis, wound healing and cancer progression. Over the years, the role of EMT in cancer progression has been heavily debated, and the requirement of this process in metastasis even has been disputed. In this review, we discuss previous discrepancies in the light of recent findings on EMT, plasticity and hybrid E/M states. Moreover, we highlight various tumor microenvironmental cues and cell intrinsic signaling pathways that induce and sustain EMT programs, plasticity and hybrid E/M states. Lastly, we discuss how recent findings on plasticity, especially on those that enable cells to switch between hybrid E/M states, have changed our understanding on the role of EMT in cancer metastasis, stemness and therapy resistance.
Diagnosing SARS-CoV-2 with Antigen Testing, Transcription-Mediated Amplification and Real-Time PCR
Authors: Dierks Sascha , Bader Oliver , Schwanbeck Julian , Groß Uwe , Weig Michael , Mese Kemal , Lugert Raimond , Bohne Wolfgang , Hahn Andreas , Feltgen Nicolas , Torkieh Setare , Denker Fenja , Lauermann Peer , Storch Marcus , Frickmann Hagen , Zautner Andreas
Published: May 2021

This study was performed as a head-to-head comparison of the performance characteristics of (1) two SARS-CoV-2-specific rapid antigen assays with real-time PCR as gold standard as well as (2) a fully automated high-throughput transcription-mediated amplification (TMA) assay and real-time PCR in a latent class analysis-based test comparison without a gold standard with several hundred samples in a low prevalence “real world” setting. Recorded sensitivity and specificity of the NADAL and the LumiraDx antigen assays and the Hologic Aptima SARS-CoV-2 TMA assay were 0.1429 (0.0194, 0.5835), 0.7644 (0.7016, 0.8174), and 0.7157 (0, 1) as well as 0.4545 (0.2022, 0.7326), 0.9954 (0.9817, 0.9988), and 0.9997 (not estimable), respectively. Agreement kappa between the positive results of the two antigen-based assays was 0.060 (0.002, 0.167) and 0.659 (0.492, 0.825) for TMA and real-time PCR. Samples with low viral load as indicated by cycle threshold (Ct) values > 30 were generally missed by both antigen assays, while 1:10 pooling suggested higher sensitivity of TMA compared to real-time PCR. In conclusion, both sensitivity and specificity speak in favor of the use of the LumiraDx rather than the NADAL antigen assay, while TMA results are comparably as accurate as PCR, when applied in a low prevalence setting.
Diagnostic Performance of Selected Baseline Electrocardiographic Parameters for Prediction of Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Kasprzak Michał , Fabiszak Tomasz , Koziński Marek , Kubica Jacek
Published: May 2021

Objective: To evaluate the diagnostic performance of selected baseline electrocardiographic (ECG) parameters as predictors of left ventricular remodeling (LVR) in patients with a first ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Methods: The study was performed as a single-center cohort study, with 249 patients (74.7% males) included in the final analysis. Nine baseline ECG parameters were evaluated, with respect to occurrence of LVR 6 months after STEMI (defined as an echocardiography-assessed relative >20% increase in end-diastolic left ventricular volume compared with the value at discharge from hospital). Results: The baseline ECG predictors of LVR, identified in univariate analysis, included the number of leads with ST-segment elevation (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.03–1.38, p = 0.0212), number of leads with Q-waves (OR 1.21, 95% CI 1.07–1.37, p = 0.0033), sum of ST-segment elevation (OR 1.04, 95% CI 1.00–1.08; p = 0.0253) and maximal ST-segment elevation (OR 1.14; 95% CI 1.00–1.29; p = 0.0446). When added to demographic, clinical and angiographic data, the number of leads with ST-segment elevation (OR 1.17, 95% CI 1.01–1.36; p = 0.0413), number of leads with Q-waves (OR 1.15, 95% CI 1.01–1.32; p = 0.0354) and the sum of ST-segment elevation (OR 1.04, 95% CI 1.00–1.08; p = 0.0331) successfully predicted development of LVR in multivariate logistic regression models. However, after inclusion of biochemical data in multivariate models, none of the electrocardiographic parameters, but increasing body weight, TIMI flow after PCI < 3 and higher maximal values of myocardial necrosis biomarker, was independently associated with the occurrence of LVR 6 months after STEMI. Conclusions: Our study demonstrates modest utility of pre-reperfusion ECG for the prediction of LVR occurrence after six months of STEMI.
Outcome of Unilateral Pulmonary Edema after Minimal-Invasive Mitral Valve Surgery: 10-Year Follow-Up
Authors: Puehler Thomas , Friedrich Christine , Lutter Georg , Kornhuber Maike , Salem Mohamed , Schoettler Jan , Ernst Markus , Saad Mohammed , Seoudy Hatim , Frank Derk , Schoeneich Felix , Cremer Jochen , Haneya Assad
Published: May 2021

The study was approved by the institutional review board (IRB) at the University Medical Center Campus Kiel, Kiel, Germany (reference number: AZ D 559/18) and registered at the German Clinical Trials Register (reference number: DRKS00022222). Objective. Unilateral pulmonary edema (UPE) is a complication after minimally invasive mitral valve surgery (MIMVS). We analyzed the impact of this complication on the short- and long-term outcome over a 10-year period. Methods. We retrospectively observed 393 MIMVS patients between 01/2009 and 12/2019. The primary endpoint was a radiographically and clinically defined UPE within the first postoperative 24 h, secondary endpoints were 30-day and long-term mortality and the percentage of patients requiring ECLS. Risk factors for UPE incidence were evaluated by logistic regression, and risk factors for mortality in the follow-up period were assessed by Cox regression. Results. Median EuroSCORE II reached 0.98% in the complete MIMVS group. Combined 30-day and in-hospital mortality after MIMVS was 2.0% with a 95, 93 and 77% survival rate after 1, 3 and 10 years. Seventy-two (18.3%) of 393 patients developed a UPE 24 h after surgery. Six patients (8.3%) with UPE required an extracorporeal life-support system. Logistic regression analysis identified a higher creatinine level, a worse LV function, pulmonary hypertension, intraoperative transfusion and a longer aortic clamp time as predictors for UPE. Combined in hospital mortality and 30-day mortality was slightly but not significantly higher in the UPE group (4.2 vs. 1.6%; p = 0.17). Predictors for mortality during follow-up were age ≥ 70 years, impaired RVF, COPD, drainage loss ≥ 800 mL and length of ventilation ≥ 48 h. During a median follow-up of 4.6 years, comparable survival between UPE and non-UPE patients was seen in our analysis after 5 years (89 vs. 88%; p = 0.98). Conclusions. In-hospital outcome with UPE after MIMVS was not significantly worse compared to non-UPE patients, and no differences were observed in the long-term follow-up. However, prolonged aortic clamp time, worse renal and left ventricular function, pulmonary hypertension and transfusion are associated with UPE.
Mobile Robot-Based Gait Training after Total Hip Arthroplasty (THA) Improves Walking in Biomechanical Gait Analysis
Authors: Röhner Eric , Mayfarth Anke , Sternitzke Christian , Layher Frank , Scheidig Andrea , Groß Horst-Michael , Matziolis Georg , Böhle Sabrina , Sander Klaus
Published: May 2021

There are multiple attempts to decrease costs in the healthcare system while maintaining a high treatment quality. Digital therapies receive increasing attention in clinical practice, mainly relating to home-based exercises supported by mobile devices, eventually in combination with wearable sensors. The aim of this study was to determine if patients following total hip arthroplasty (THA) could benefit from gait training on crutches conducted by a mobile robot in a clinical setting. Method: This clinical trial was conducted with 30 patients following total hip arthroplasty. Fifteen patients received the conventional physiotherapy program in the clinic (including 5 min of gait training supported by a physiotherapist). The intervention group of 15 patients passed the same standard physiotherapy program, but the 5-min gait training supported by a physiotherapist was replaced by 2 × 5 min of gait training conducted by the robot. Length of stay of the patients was set to five days. Biomechanical gait parameters of the patients were assessed pre-surgery and upon patient discharge. Results: While before surgery no significant difference in gait parameters was existent, patients from the intervention group showed a significant higher absolute walking speed (0.83 vs. 0.65 m/s, p = 0.029), higher relative walking speed (0.2 vs. 0.16 m/s, p = 0.043) or shorter relative cycle time (3.35 vs. 3.68 s, p = 0.041) than the patients from the control group. Conclusion: The significant higher walking speed of patients indicates that such robot-based gait training on crutches may shorten length of stay (LOS) in acute clinics. However, the number of patients involved was rather small, thus calling for further studies.
Influence of Retinal Microsecond Pulse Laser Treatment in Central Serous Chorioretinopathy: A Short-Term Optical Coherence Tomography Angiography Study
Authors: Prasuhn Michelle , Miura Yoko , Tura Aysegül , Rommel Felix , Kakkassery Vinodh , Sonntag Svenja , Grisanti Salvatore , Ranjbar Mahdy
Published: May 2021

Background: Central serous chorioretinopathy (CSC) is a common macular condition characterized by detachment of the neuroretina and is a frequent cause of central vision loss in adults. Among the various therapeutic strategies, subthreshold microsecond pulsed laser (SML) treatment has become a useful option. Despite the suggested involvement of choroidal circulatory disturbances in CSC, the effects of this treatment on macular microperfusion have not been fully evaluated yet. Herein, we report the impact of SML on retinal and choroidal microvascular flow using non-invasive optical coherence tomography (OCT) angiography (OCTA). Methods: In this study, CSC patients with persistent subretinal fluid (SRF) with or without secondary choroidal neovascularization (CNV) were included (referred to as the pachychoroid neovasculopathy (PNV) group and the CSC group, respectively). SML was conducted using a yellow (577 nm) laser with a duty cycle of 10%, spot size of 200 µm and duration of 200 ms. Best corrected visual acuity (BCVA) as well as OCT and OCTA images were evaluated at baseline and 4 weeks after SML. OCTA parameters of interest included full retinal perfusion (FRP), choriocapillaris perfusion (CCP), Sattler’s layer perfusion (SLP), and Haller’s layer perfusion (HLP), which were evaluated longitudinally and compared to unaffected fellow eyes. Results: 27 affected eyes and 17 fellow eyes from 27 patients were included. Before treatment, central retinal thickness (CRT) and subfoveal choroidal thickness (SFCT) of affected eyes were significantly larger than in fellow eyes. Four weeks after SML, CRT decreased significantly, whereas perfusion parameters did not change. In subgroup analyses, the CSC group showed a significant decrease in SFCT, whereas the PNV group did not despite the decrease in CRT. Conclusion: Our results suggest that the SML may affect the SFCT of the CSC, but not the PNV patients at least within four weeks following treatment. This effect seems to be independent of the change in choroidal perfusion measured with OCTA.
Tolerability and Efficacy of s.c. IgG Self-Treatment in ME/CFS Patients with IgG/IgG Subclass Deficiency: A Proof-of-Concept Study
Authors: Scheibenbogen Carmen , Sotzny Franziska , Hartwig Jelka , Bauer Sandra , Freitag Helma , Wittke Kirsten , Doehner Wolfram , Scherbakov Nadja , Loebel Madlen , Grabowski Patricia
Published: May 2021

Background: Chronic fatigue syndrome (ME/CFS) is a complex disease frequently triggered by infections. IgG substitution may have therapeutic effect both by ameliorating susceptibility to infections and due to immunomodulatory effects. Methods: We conducted a proof of concept open trial with s.c. IgG in 17 ME/CFS patients suffering from recurrent infections and mild IgG or IgG subclass deficiency to assess tolerability and efficacy. Patients received s.c. IgG therapy of 0.8 g/kg/month for 12 months with an initial 2 months dose escalation phase of 0.2 g and 0.4 g/kg/month. Results: Primary outcome was improvement of fatigue assessed by Chalder Fatigue Scale (CFQ; decrease ≥ 6 points) and of physical functioning assessed by SF-36 (increase ≥ 25 points) at month 12. Of 12 patients receiving treatment per protocol 5 had a clinical response at month 12. Two additional patients had an improvement according to this definition at months 6 and 9. In four patients treatment was ceased due to adverse events and in one patient due to disease worsening. We identified LDH and soluble IL-2 receptor as potential biomarker for response. Conclusion: Our data indicate that self-administered s.c. IgG treatment is feasible and led to clinical improvement in a subset of ME/CFS patients.
Task-Oriented Circuit Training as an Alternative to Ergometer-Type Aerobic Exercise Training after Stroke
Authors: Kelly Liam P. , Devasahayam Augustine J. , Chaves Arthur R. , Curtis Marie E. , Randell Edward W. , McCarthy Jason , Basset Fabien A. , Ploughman Michelle
Published: May 2021

Moderate-intensity aerobic exercise training is an important treatment strategy to enhance functional recovery and decrease cardiometabolic risk factors after stroke. However, stroke related impairments limit access to ergometer-type exercise. The aims of the current study were (1) to evaluate whether our task-oriented circuit training protocol (intermittent functional training; IFT) could be used to sustain moderate-intensity aerobic workloads over a 10-week intervention period, and (2) to investigate its preliminary effects on cardiorespiratory fitness and metabolic profiles compared to constant-load ergometer-type exercise (CET). Forty chronic hemiparetic stroke survivors were randomized to receive 30 sessions of IFT or CET over ten weeks. Similar proportions of participants were randomized to IFT (7/19) and CET (9/18) sustained workloads associated with moderate-intensity aerobic exercise over the study period (p = 0.515). However, CET was associated with more substantial changes in maximal oxygen uptake (MD = 2.79 mL min−1 kg−1 CI: 0.84 to 4.74) compared to IFT (MD = 0.62 mL min−1 kg−1 CI: −0.38 to 1.62). Pre to post changes in C-reactive protein (−0.9 mg/L; p =0.017), short-term glycemia (+14.7 mol/L; p = 0.026), and resting whole-body carbohydrate oxidation (+24.2 mg min−1; p = 0.046) were observed when considering both groups together. Accordingly, IFT can replicate the aerobic intensities sustained during traditional ergometer-type exercise training. More work is needed to evaluate the dose–response effects of such task-oriented circuit training protocols on secondary prevention targets across the continuum of stroke recovery.
Brolucizumab for Choroidal Neovascular Membrane with Pigment Epithelial Tear and Subretinal Fluid
Authors: Bilgic Alper , Kodjikian Laurent , Vasavada Shail , Jha Shyamal , Srivastava Samaresh , Sudhalkar Aditya , Mathis Thibaud
Published: May 2021

The aim of this study was to determine the utility of brolucizumab in the management of choroidal neovessels (CNV) with a retinal pigment epithelial (RPE) tear and subretinal fluid. We used a case series of patients with CNV who developed an RPE tear either spontaneously or following an intravitreal injection. All patients received intravitreal brolucizumab as primary or switch therapy. Appropriate data were collected. Follow-up was one year. The paired t-test was used to determine the significance of the results. The primary outcome measure was the change in best corrected visual acuity (BCVA). Secondary outcome measures were the change in subretinal fluid and complications, if any. A total of five patients were included in the analysis. The age range was 67−74 years and baseline BCVA was from 20/80 to 20/100. On average, all patients showed improvement in BCVA (p = 0.012) and also showed a significant anatomical improvement (p = 0.03). None of the patients had any complications, and all patients responded to additional anti-VEGF injections. In conclusion, all patients showed significant visual and anatomical improvement with brolucizumab; no complications were noted. All patients, including those who received switch, demonstrated a favorable anatomical and visual response to intravitreal brolucizumab without safety concerns.
Do-It-Yourself Preoperative High-Resolution Ultrasound-Guided Flap Design of the Superficial Circumflex Iliac Artery Perforator Flap (SCIP)
Authors: Schiltz Daniel , Lenhard Jasmin , Klein Silvan , Anker Alexandra , Lonic Daniel , Heidekrueger Paul I. , Prantl Lukas , Jung Ernst-Michael , Platz Batista Da Silva Natascha , Kehrer Andreas
Published: May 2021

The superficial circumflex iliac artery perforator (SCIP) flap is a well-documented, thin, free tissue flap with a minimal donor site morbidity, and has the potential to become the new method for resurfacing moderate-size skin defects. The aim of this study is to describe an easy, reliable, systematic, and standardized approach for preoperative SCIP flap design and perforator characterization, using color-coded duplex sonography (CCDS). A list of customized settings and a straightforward algorithm are presented, which are easily applied by an operator with minimal experience. Specific settings for SCIP flap perforator evaluation were investigated and tested on 12 patients. Deep and superficial superficial circumflex iliac artery (SCIA) branches, along with their corresponding perforators and cutaneous veins, were marked individually with a permanent marker and the anatomy was verified intraoperatively. From this, a simplified procedure for preoperative flap design of the SCIP flap was developed. Branches could be localized and evaluated in all patients. A preoperative structured procedure for ultrasonically guided flap design of the SCIP flap is described. A 100% correlation between the number and emergence points of the branches detected by preoperative CCDS mapping and the intraoperative anatomy was found.
The Role of Surgical Resection and Liver Transplantation for the Treatment of Intrahepatic Cholangiocarcinoma
Authors: Panayotova Guergana , Guerra Jarot , Guarrera James V. , Lunsford Keri E.
Published: May 2021

Intrahepatic cholangiocarcinoma (iCCA) is a rare and complex malignancy of the biliary epithelium. Due to its silent presentation, patients are frequently diagnosed late in their disease course, resulting in poor overall survival. Advances in molecular profiling and targeted therapies have improved medical management, but long-term survival is rarely seen with medical therapy alone. Surgical resection offers a survival advantage, but negative oncologic margins are difficult to achieve, recurrence rates are high, and the need for adequate future liver remnant limits the extent of resection. Advances in neoadjuvant and adjuvant treatments have broadened patient treatment options, and these agents are undergoing active investigation, especially in the setting of advanced, initially unresectable disease. For those who are not able to undergo resection, liver transplantation is emerging as a potential curative therapy in certain cases. Patient selection, favorable tumor biology, and a protocolized, multidisciplinary approach are ultimately necessary for best patient outcomes. This review will discuss the current surgical management of locally advanced, liver-limited intrahepatic cholangiocarcinoma as well as the role of liver transplantation for select patients with background liver disease.
Associations between High-Density Lipoprotein Functionality and Major Adverse Cardiovascular Events in Patients Who Have Undergone Coronary Computed Tomography Angiography
Authors: Inoue Hiroko , Shiga Yuhei , Norimatsu Kenji , Tashiro Kohei , Futami Makito , Suematsu Yasunori , Sugihara Makoto , Nishikawa Hiroaki , Katsuda Yousuke , Miura Shin-ichiro
Published: May 2021

The present study aimed to investigate the associations between high-density lipoprotein (HDL) functionality and major adverse cardiovascular events (MACE) in patients who have undergone coronary computed tomography angiography (CCTA). We performed a prospective cohort study and enrolled 151 patients who underwent CCTA and had a follow-up of up to 5 years. We measured cholesterol efflux capacity (CEC), caspase-3/7 activity and monocyte chemoattractant protein-1 (MCP-1) secretion as bioassays of HDL functionality. The patients were divided into MACE(−) (n = 138) and MACE(+) (n = 13) groups. While there was no significant difference in %CEC, caspase-3/7 activity or MCP-1 secretion between the MACE(−) and MACE(+) groups, total CEC and HDL cholesterol (HDL-C) in the MACE(+) group were significantly lower than those in the MACE(−) group. Total CEC was correlated with HDL-C. A receiver-operating characteristic curve analysis showed that there was no significant difference between the areas under the curves for total CEC and HDL-C. In conclusion, total CEC in addition to HDL-C, but not %CEC, was associated with the presence of MACE. On the other hand, HDL functionality with regard to anti-inflammatory and anti-apoptosis effects was not associated with MACE.
Visual Outcome after Intravitreal Anti-VEGF Therapy for Macular Neovascularisation Secondary to Sorsby’s Fundus Dystrophy: A Systematic Review
Authors: Baston Arthur , Gerhardt Christin , Zandi Souska , Garweg Justus G.
Published: May 2021

The aim of this paper is to summarise our own and to review published experience regarding the long-term outcome of intravitreal treatment for macular neovascularisation (MNV) secondary to Sorsby’s fundus dystrophy (SFD). A systematic literature search using the MeSH terms [Sorsby] and [anti-vascular endothelial growth factor (VEGF)] was conducted in NCBI/PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ScienceDirect, Google Scholar and ClinicalTrials.gov to identify publications reporting anti-VEGF treatment outcomes in SFD. Treatment outcomes were extracted for this meta-analysis from 14 publications and an own patient reporting a total of 31 cases with a mean follow-up (FU) of 54 months. Both eyes were affected in ten (32.3%) instances. Heterogenous reporting limited the comparability of the outcomes. All papers in common, however, reported satisfied to excellent responses to anti-VEGF therapy if patients were diagnosed and treated immediately after onset of symptoms. Of 20 eyes, for which visual acuity was reported before and after treatment, five worsened and seven improved by more than 1 line, whereas eight eyes maintained their function by end of the follow up, and 11 eyes (55%) maintained a driving vision (Snellen VA ≥ 0.5). Of six eyes with a VA < 0.5, VA improved in one to VA ≥ 0.5, whereas of 14 eyes with an initial VA ≥ 0.5, this dropped to <0.5 despite therapy. In MNV secondary to SFD, the delay between first symptoms and access to anti-VEGF treatment determines subretinal scar formation and thereby, functional prognosis. If treated early, this is generally favourable under regular controls and a consequent anti-VEGF treatment of MNV activity.
Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex
Authors: Innocenzi Elisa , Cariati Ida , De Domenico Emanuela , Tiberi Erika , D’Arcangelo Giovanna , Verdile Veronica , Paronetto Maria Paola , Tancredi Virginia , Barchi Marco , Rossi Pellegrino , Sette Claudio , Grimaldi Paola
Published: May 2021

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.
Thermal Effects on Surface and Subsurface Modifications in Laser-Combined Deep Rolling
Authors: Zmich Robert , Meyer Daniel
Published: May 2021

Knowledge of the relationships between thermomechanical process loads and the resulting modifications in the surface layer enables targeted adjustments of the required surface integrity independent of the manufacturing process. In various processes with thermomechanical impact, thermal and mechanical loads act simultaneously and affect each other. Thus, the effects on the modifications are interdependent. To gain a better understanding of the interactions of the two loads, it is necessary to vary thermal and mechanical loads independently. A new process of laser-combined deep rolling can fulfil exactly this requirement. The presented findings demonstrate that thermal loads can support the generation of residual compressive stresses to a certain extent. If the thermal loads are increased further, this has a negative effect on the surface layer and the residual stresses are shifted in the direction of tension. The results show the optimum range of thermal loads to further increase the compressive residual stresses in the surface layer and allow to gain a better understanding of the interactions between thermal and mechanical loads.
Identification of New Sub-Fossil Diatoms Flora in the Sediments of Suncheonman Bay, Korea
Authors: Park Mirye , Lee Sang Deuk , Lee Hoil , Lee Jin-Young , Kwon Daeryul , Choi Jeong-Min
Published: May 2021

Suncheonman Bay, Korea’s most representative estuary, is an invasive coastal wetland composed of 22.6 km2 of tidal flats surrounded by the Yeosu and Goheung Peninsulas. In January 2006, this region was registered in the Ramsar Convention list in Korea, representing the first registered wetland. Estuaries are generally known to have high species diversity. In particular, several studies have been conducted on planktonic and epipelic diatoms as primary producers. Suncheonman Bay has already been involved in many biological and geochemical studies, but fossil diatoms have not been evaluated. Therefore, we investigated fossil diatoms in Suncheonman Bay and introduced sub-fossil diatoms recorded in Korea. One sedimentary core has been extracted in 2018. We identified 87 diatom taxa from 52 genera in the SCW03 core sample. Of these, six species represent new records in Korea: Cymatonitzschia marina, Fallacia hodgeana, Navicula mannii, Metascolioneis tumida, Surirella recedens, and Thalassionema synedriforme. These six newly recorded diatom species were examined by light microscopy and scanning electron microscopy. The ecological habitats for all the investigated taxa are presented.
ANN-Based Decision Making in Station Keeping for Geotechnical Drilling Vessel
Authors: Ramasamy Murugan , Hannan Mohammed Abdul , Ahmed Yaseen Adnan , Dev Arun Kr
Published: May 2021

Offshore vessels (OVs) often require precise station-keeping and some vessels, for example, vessels involved in geotechnical drilling, generally use Spread Mooring (SM) or Dynamic Positioning (DP) systems. Most of these vessels are equipped with both systems to cover all ranges of water depths. However, determining which system to use for a particular operational scenario depends on many factors and requires significant balancing in terms of cost-benefit. Therefore, this research aims to develop a platform that will determine the cost factors for both the SM and DP station-keeping systems. Operational information and cost data are collected for several field operations, and Artificial Neural Networks (ANN) are trained using those data samples. After that, the trained ANN is used to predict the components of cost for any given environmental situation, fieldwork duration and water depth. Later, the total cost is investigated against water depth for both DP and SM systems to determine the most cost-effective option. The results are validated using two operational scenarios for a specific geotechnical vessel. This decision-making algorithm can be further developed by adding up more operational data for various vessels and can be applied in the development of sustainable decision-making business models for OVs operators.