bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case Study on the Use of Virtual Fencing to Intensively Graze Angus Heifers Using Moving Front and Back-Fences
Authors: Verdon Megan , Horton Brian , Rawnsley Richard
Published: April 2021

Virtual fencing contains and controls grazing cattle using sensory cues rather than physical fences. The technology comprises a neckband-mounted device that delivers an audio cue when the animal nears a virtual boundary that has been set via global positioning system, followed by an electrical stimulus if it walks beyond the boundary. Virtual fencing has successfully been used to intensively graze cattle using a simple virtual front-fence, but a more complex intensive grazing system comprising moving virtual front and back-fences has not been assessed. We studied the effectiveness of virtual fencing technology to contain groups of Angus heifers within grazing cells defined by semi-permanent electric side-fences and virtual front and back-fences, compared to groups of heifers contained in cells defined only by electric fencing. Four groups of 10 Angus heifers were randomly allocated to a “control” (grazed with a conventional electric front and back-fence, n = 2 groups) or “virtual fence” treatment (grazed with a virtual front and back-fence, n = 2 groups). The groups of heifers grazed four adjacent experimental paddocks that were established using TechnoGrazing™ infrastructure. An estimated 9.5 kg pasture DM/heifer.day was offered in each of three 3 day allocations (9 day study period). Data collected include cues delivered by the neckbands, time beyond the virtual boundaries, pasture consumption for each allocation and heifer live weight changes over the study period. The virtual front and back-fences successfully contained one group of heifers in their grazing cell, but the second group of heifers spent an increasing amount of time in the exclusion zone during the second and third allocations and consequently received an increasing number of audio and electrical stimuli. There were no effects of electric or virtual-fence treatment on live weight change or pasture utilization. By grazing heifers in adjacent paddocks our experimental design may have produced a motivation for some heifers to cross the virtual boundary to regain close contact with familiar conspecifics. Despite this, valuable learnings were gained from this study. Most notably, virtual fencing should not be used to manage cattle that have close visual contact to other mobs. We conclude that the successful application of virtual fencing technology needs to accommodate the natural behaviors of cattle.
Data Driven Cell Cycle Model to Quantify the Efficacy of Cancer Therapeutics Targeting Specific Cell-Cycle Phases From Flow Cytometry Results
Authors: James David W. , Filby Andrew , Brown M. Rowan , Summers Huw D. , Francis Lewis W. , Rees Paul
Published: April 2021

Many chemotherapeutic drugs target cell processes in specific cell cycle phases. Determining the specific phases targeted is key to understanding drug mechanism of action and efficacy against specific cancer types. Flow cytometry experiments, combined with cell cycle phase and division round specific staining, can be used to quantify the current cell cycle phase and number of mitotic events of each cell within a population. However, quantification of cell interphase times and the efficacy of cytotoxic drugs targeting specific cell cycle phases cannot be determined directly. We present a data driven computational cell population model for interpreting experimental results, where in-silico populations are initialized to match observable results from experimental populations. A two-stage approach is used to determine the efficacy of cytotoxic drugs in blocking cell-cycle phase transitions. In the first stage, our model is fitted to experimental multi-parameter flow cytometry results from untreated cell populations to identify parameters defining probability density functions for phase transitions. In the second stage, we introduce a blocking routine to the model which blocks a percentage of attempted transitions between cell-cycle phases due to therapeutic treatment. The resulting model closely matches the percentage of cells from experiment in each cell-cycle phase and division round. From untreated cell populations, interphase and intermitotic times can be inferred. We then identify the specific cell-cycle phases that cytotoxic compounds target and quantify the percentages of cell transitions that are blocked compared with the untreated population, which will lead to improved understanding of drug efficacy and mechanism of action.
Enhancement of Migration and Tenogenic Differentiation of Macaca Mulatta Tendon-Derived Stem Cells by Decellularized Tendon Hydrogel
Authors: Ning Liang-Ju , Zhang Ya-Jing , Zhang Yan-Jing , Zhu Min , Ding Wei , Jiang Yan-Lin , Zhang Yi , Luo Jing-Cong , Qin Ting-Wu
Published: April 2021

Decellularized tendon hydrogel from human or porcine tendon has been manufactured and found to be capable of augmenting tendon repair in vivo. However, no studies have clarified the effect of decellularized tendon hydrogel upon stem cell behavior. In the present study, we developed a new decellularized tendon hydrogel (T-gel) from Macaca mulatta, and investigated the effect of T-gel on the proliferation, migration and tenogenic differentiation of Macaca mulatta tendon-derived stem cells (mTDSCs). The mTDSCs were first identified to have universal stem cell characteristics, including clonogenicity, expression of mesenchymal stem cell and embryonic stem cell markers, and multilineage differentiation potential. Decellularization of Macaca mulatta Achilles tendons was confirmed to be effective by histological staining and DNA quantification. The resultant T-gel exhibited highly porous structure or similar nanofibrous structure and approximately swelling ratio compared to the collagen gel (C-gel). Interestingly, stromal cell-derived factor-1 (SDF-1) and fibromodulin (Fmod) inherent in the native tendon extracellular matrix (ECM) microenvironment were retained and the values of SDF-1 and Fmod in the T-gel were significantly higher than those found in the C-gel. Compared with the C-gel, the T-gel was found to be cytocompatible with NIH-3T3 fibroblasts and displayed good histocompatibility when implanted into rat subcutaneous tissue. More importantly, it was demonstrated that the T-gel supported the proliferation of mTDSCs and significantly promoted the migration and tenogenic differentiation of mTDSCs compared to the C-gel. These findings indicated that the T-gel, with its retained nanofibrous structure and some bioactive factors of native tendon ECM microenvironment, represents a promising hydrogel for tendon regeneration.
FOXC1 Negatively Regulates DKK1 Expression to Promote Gastric Cancer Cell Proliferation Through Activation of Wnt Signaling Pathway
Authors: Jiang Jiang , Li Jianfang , Yao Weiwu , Wang Wenfang , Shi Bowen , Yuan Fei , Dong Jingyan , Zhang Huan
Published: April 2021

Gastric cancer (GC), characterized by uncontrolled growth, is a common malignant tumor of the digestive system. The Wnt signaling pathway plays an important role in the tumorigenesis and proliferation of GC. Many studies on this signaling pathway have focused on its intracellular regulatory mechanism, whereas little attention has been given to extracellular regulatory factors. Dickkopf-1 (Dkk1) is a secretory glycoprotein, and it can bind inhibit activation of the Wnt pathway. However, the regulation and mechanism of DKK1 in the proliferation of GC remain unclear. FOXC1 plays an important role in organ development and tumor growth, but its role in GC tumor growth remains unknown. In this study, we found that the FOXC1 is highly expressed in patients with GC and high expression of FOXC1 correlates to poor prognosis. In addition, we found that the Wnt signaling pathway in GC cells with high FOXC1 expression was strongly activated. FOXC1 negatively regulates DKK1 expression by binding to its promoter region, thereby promoting the activation of Wnt pathway. FOXC1 can also form a complex with unphosphorylated β-catenin protein in the cytoplasm and then dissociates from β-catenin in the nucleus, thereby promoting the entry of β-catenin into the nucleus and regulating expression of c-MYC, which promotes the proliferation of GC cells. Our study not only reveals the function and mechanism of FOXC1 in GC, but also provides a potential target for clinic GC treatment.
Blood Omega-3 Fatty Acids Are Inversely Associated With Albumin-Creatinine Ratio in Young and Healthy Adults (The Omega-Kid Study)
Authors: Filipovic Mark G. , Reiner Martin F. , Rittirsch Saskia , Irincheeva Irina , Aeschbacher Stefanie , Grossmann Kirsten , Risch Martin , Risch Lorenz , Limacher Andreas , Conen David , Beer Juerg H.
Published: April 2021

Background: Omega-3 fatty acids are associated with a lower risk of cardiovascular disease (CVD) and with beneficial effects on CV risk factors. The albumin-creatinine ratio (ACR) is a risk factor for CVD, all-cause mortality and accelerated glomerular filtration rate (GFR) decline in the general population. We aimed to investigate the association between n-3 PUFAS and ACR in heathy individuals with preserved GFR.

Design and Methods: The present cross-sectional analysis is part of the GAPP study, a population-based cohort of healthy adults aged 25–41 years. Individuals with known CVD, diabetes, or a BMI >35 kg/m2 were excluded. eGFR was calculated according to the combined Creatinine/Cystatin C CKD-EPI formula. ACR was obtained from a fasting morning urine sample. The Omega-3 Index (relative amount of EPA and DHA of total fatty acids in %) was obtained from whole blood aliquots.

Results: Overall, 2001 participants (median age 37 years IQR 31; 40, 53% female) were included in this analysis. Median Omega-3 Index was 4.59 (IQR 4.06; 5.25) and median eGFR 111 ml/min/1.73 m2 (IQR 103; 118). Median ACR was 0.14 mg/mmol (IQR 0; 0.43). We found a significant inverse association of the Omega-3 Index with ACR (ratio 0.84, 95%CI 0.73–0.96; p = 0.011) which remained after comprehensive adjustment (ratio 0.86, 95%CI 0.74–1.00; p = 0.048). No association of the Omega-3 Index with eGFR was found. The adjusted difference in eGFR per 1-unit increase in Omega3-Index was −0.21 (95%CI −0.76; 0.35; p = 0.47).

Conclusions: A higher Omega-3 Index was significantly associated with lower ACR in this young and healthy population with preserved eGFR. Omega-3 fatty acids may exhibit cardio- and nephroprotective effects in healthy individuals through modulation of ACR.
Long Term Outcome of Postoperative Atrial Fibrillation After Cardiac Surgery—A Propensity Score-Matched Cohort Analysis
Authors: Hsu Jung-Chi , Huang Chen-Yu , Chuang Shu-Lin , Yu Hsu-Yu , Chen Yih-Sharng , Wang Chih-Hsien , Lin Lian-Yu
Published: April 2021

Background: Postoperative atrial fibrillation (POAF) results in a longer hospital stay and excess mortality. However, whether POAF would increase stroke rate has been debated for years. When and how long should anticoagulation be used to prevent stroke are unknown. In the study, we planned to investigate the clinical demographics and long-term outcomes of POAF after cardiac surgery in a single-center cohort.

Methods: The cohort study used a database from National Taiwan University Hospital, a single tertiary medical center in Taiwan, between 2007 and 2017, to identify patients with prior normal sinus rhythm developing POAF after cardiac surgery. Patients without POAF after cardiac surgery were used as controls. Propensity score matching with 1:1 ratio and Cox regression models were employed to estimate the risk of transient ischemic accident (TIA) or ischemic stroke.

Results: From 2007 to 2017, a total of 8,374 patients received open-heart surgery, in which 1,585 patients with a history of AF were excluded. The overall incidence of TIA/ischemic stroke was 3.9% in a median 9.2-years of follow-up. After propensity matching, 1,965 matched paired subjects were included for analysis. Postoperative atrial fibrillation was associated with an increased risk of future AF [Hazard ratio (HR) 1.40, 95% confidence interval (95%CI) = 1.09–1.79, p = 0.008] and heart failure (HF) hospitalization (HR 1.58, 95%CI 1.23–2.04, p < 0.001); however, POAF did not significantly correlate with the risk of TIA/ischemic stroke (HR 1.17, 95%CI 0.85–1.60, p = 0.043). Kaplan-Meier analysis showed that POAF was a significant predictor for future AF, HF hospitalization, and overall mortality, but not for TIA/ischemic stroke.

Conclusion: In the Asian population, POAF after cardiac surgery increased the risk of future AF, HF, and overall mortality, but was not associated with future TIA/ischemic stroke.
Epigenetic Mechanisms Involved in the Cardiovascular Toxicity of Anticancer Drugs
Authors: Papazoglou Panagiota , Peng Luying , Sachinidis Agapios
Published: April 2021

The cardiovascular toxicity of anticancer drugs promotes the development of cardiovascular diseases. Therefore, cardiovascular toxicity is an important safety issue that must be considered when developing medications and therapeutic applications to treat cancer. Among anticancer drugs, members of the anthracycline family, such as doxorubicin, daunorubicin and mitoxantrone, are known to cause cardiotoxicity and even heart failure. Using human-induced pluripotent stem cell-derived cardiomyocytes in combination with “Omic” technologies, we identified several cardiotoxicity mechanisms and signal transduction pathways. Moreover, these drugs acted as cardiovascular toxicants through a syndrome of mechanisms, including epigenetic ones. Herein, we discuss the main cardiovascular toxicity mechanisms, with an emphasis on those associated with reactive oxygen species and mitochondria that contribute to cardiotoxic epigenetic modifications. We also discuss how to mitigate the cardiotoxic effects of anticancer drugs using available pharmaceutical “weapons.”
Clinical Value of Complex Echocardiographic Left Ventricular Hypertrophy Classification Based on Concentricity, Mass, and Volume Quantification
Authors: Barbieri Andrea , Albini Alessandro , Maisano Anna , De Mitri Gerardo , Camaioni Giovanni , Bonini Niccolò , Mantovani Francesca , Boriani Giuseppe
Published: April 2021

Echocardiography is the most validated, non-invasive and used approach to assess left ventricular hypertrophy (LVH). Alternative methods, specifically magnetic resonance imaging, provide high cost and practical challenges in large scale clinical application. To include a wide range of physiological and pathological conditions, LVH should be considered in conjunction with the LV remodeling assessment. The universally known 2-group classification of LVH only considers the estimation of LV mass and relative wall thickness (RWT) to be classifying variables. However, knowledge of the 2-group patterns provides particularly limited incremental prognostic information beyond LVH. Conversely, LV enlargement conveys independent prognostic utility beyond LV mass for incident heart failure. Therefore, a 4-group LVH subdivision based on LV mass, LV volume, and RWT has been recently suggested. This novel LVH classification is characterized by distinct differences in cardiac function, allowing clinicians to distinguish between different LV hemodynamic stress adaptations in various cardiovascular diseases. The new 4-group LVH classification has the advantage of optimizing the LVH diagnostic approach and the potential to improve the identification of maladaptive responses that warrant targeted therapy. In this review, we summarize the current knowledge on clinical value of this refinement of the LVH classification, emphasizing the role of echocardiography in applying contemporary proposed indexation methods and partition values.
Deciphering the Role of Endolysosomal Ca2+ Channels in Immunity
Authors: Alharbi Abeer F. , Parrington John
Published: April 2021

The role of endolysosomal Ca2+ signalling in immunity has been a subject of increasing interest in recent years. Here, we discuss evolving knowledge relating to the contribution of endolysosomal Ca2+ channels that include TPCs, TRPMLs, and P2X4R in physiological processes related to innate and adaptive immunity—including phagocytosis, inflammation, cytokine/chemokine release, dendritic, natural killer, and T cell activation and migration—and we underscore the paucity of clinical studies in this field. Emerging biomedical and translational data have led to important new insights into the critical roles of these channels in immune cell function and the regulation of innate and adaptive immune responses. The evolving immunological significance of endolysosomal Ca2+ signalling warrants further investigations to better characterize the roles of these channels in immunity in order to expand our knowledge about the pathology of inflammatory and autoimmune diseases and develop endolysosomal Ca2+ channels as viable biomarkers and therapeutic and preventive targets for remodelling the immune response.
How Microbes Defend Themselves From Incoming Hydrogen Peroxide
Authors: Sen Ananya , Imlay James A.
Published: April 2021

Microbes rely upon iron as a cofactor for many enzymes in their central metabolic processes. The reactive oxygen species (ROS) superoxide and hydrogen peroxide react rapidly with iron, and inside cells they can generate both enzyme and DNA damage. ROS are formed in some bacterial habitats by abiotic processes. The vulnerability of bacteria to ROS is also apparently exploited by ROS-generating host defense systems and bacterial competitors. Phagocyte-derivedO2−can toxify captured bacteria by damaging unidentified biomolecules on the cell surface; it is unclear whether phagocytic H2O2, which can penetrate into the cell interior, also plays a role in suppressing bacterial invasion. Both pathogenic and free-living microbes activate defensive strategies to defend themselves against incoming H2O2. Most bacteria sense the H2O2viaOxyR or PerR transcription factors, whereas yeast uses the Grx3/Yap1 system. In general these regulators induce enzymes that reduce cytoplasmic H2O2concentrations, decrease the intracellular iron pools, and repair the H2O2-mediated damage. However, individual organisms have tailored these transcription factors and their regulons to suit their particular environmental niches. Some bacteria even contain both OxyR and PerR, raising the question as to why they need both systems. In lab experiments these regulators can also respond to nitric oxide and disulfide stress, although it is unclear whether the responses are physiologically relevant. The next step is to extend these studies to natural environments, so that we can better understand the circumstances in which these systems act. In particular, it is important to probe the role they may play in enabling host infection by microbial pathogens.
A Review on Synthesis and Optoelectronic Applications of Nanostructured ZnO
Authors: Shahzad Shazrah , Javed Sofia , Usman Muhammad
Published: April 2021

Nanostructured ZnO has gained a lot of interest as a suitable material for various applications, especially sensing, energy conversion, and storage. ZnO nanostructures can be synthesized in several ways. It is one of the materials that can be prepared in a variety of morphologies including hierarchical nanostructures. This review article presents a review of current research activities on the growth of ZnO Nanorods. The article covers various water-based routes of synthesis and is further characterized by the type of substrate used for the growth. The growth factors involved in the hydrothermal and chemical bath deposition methods are discussed. These factors include the variety of precursors, time, temperature, and the seeding method employed. At the end, applications such as gas sensing and improvement in Opto-electric properties are discussed.
Understanding the Impact of Machine Learning Models on the Performance of Different Flexible Strain Sensor Modalities
Authors: Hannigan Brett C. , Cuthbert Tyler J. , Geng Wanhaoyi , Tavassolian Mohammad , Menon Carlo
Published: April 2021

Fibre strain sensors commonly use three major modalities to transduce strain—piezoresistance, capacitance, and inductance. The electrical signal in response to strain differs between these sensing technologies, having varying sensitivity, maximum measurable loading rate, and susceptibility to deleterious effects like hysteresis and drift. The wide variety of sensor materials and strain tracking applications makes it difficult to choose the best sensor modality for a wearable device when considering signal quality, cost, and difficulty of manufacture. Fibre strain sensor samples employing the three sensing mechanisms are fabricated and subjected to strain using a tensile tester. Their mechanical and electrical properties are measured in response to strain profiles designed to exhibit particular shortcomings of sensor behaviour. Using these data, the sensors are compared to identify materials and sensing technologies well suited for different textile motion tracking applications. Several regression models are trained and validated on random strain pattern data, providing guidance for pairing each sensor with a model architecture that compensates for non-ideal effects. A thermoplastic elastomer-core piezoresistive sensor had the highest sensitivity (average gauge factor: 12.6) and a piezoresistive sensor of similar construction with a polyether urethane-urea core had the largest bandwidth, capable of resolving strain rates above 300% s−1 with 36% signal amplitude attenuation. However, both piezoresistve sensors suffered from larger hysteresis and drift than a coaxial polymer sensor using the capacitive strain sensing mechanism. Machine learning improved the piezoresistive sensors’ root-mean-squared error when tracking a random strain signal by up to 58% while maintaining their high sensitivity, bandwidth, and ease of interfacing electronically.
Microbiome Data Analysis by Symmetric Non-negative Matrix Factorization With Local and Global Regularization
Authors: Zhao Junmin , Ma Yuanyuan , Liu Lifang
Published: April 2021

A network is an efficient tool to organize complicated data. The Laplacian graph has attracted more and more attention for its good properties and has been applied to many tasks including clustering, feature selection, and so on. Recently, studies have indicated that though the Laplacian graph can capture the global information of data, it lacks the power to capture fine-grained structure inherent in network. In contrast, a Vicus matrix can make full use of local topological information from the data. Given this consideration, in this paper we simultaneously introduce Laplacian and Vicus graphs into a symmetric non-negative matrix factorization framework (LVSNMF) to seek and exploit the global and local structure patterns that inherent in the original data. Extensive experiments are conducted on three real datasets (cancer, cell populations, and microbiome data). The experimental results show the proposed LVSNMF algorithm significantly outperforms other competing algorithms, suggesting its potential in biological data analysis.
Cognitive and Structural Correlates of Conversational Speech Timing in Mild Cognitive Impairment and Mild-to-Moderate Alzheimer’s Disease: Relevance for Early Detection Approaches
Authors: De Looze Céline , Dehsarvi Amir , Crosby Lisa , Vourdanou Aisling , Coen Robert F. , Lawlor Brian A. , Reilly Richard B.
Published: April 2021

Background: Increasing efforts have focused on the establishment of novel biomarkers for the early detection of Alzheimer’s disease (AD) and prediction of Mild Cognitive Impairment (MCI)-to-AD conversion. Behavioral changes over the course of healthy ageing, at disease onset and during disease progression, have been recently put forward as promising markers for the detection of MCI and AD. The present study examines whether the temporal characteristics of speech in a collaborative referencing task are associated with cognitive function and the volumes of brain regions involved in speech production and known to be reduced in MCI and AD pathology. We then explore the discriminative ability of the temporal speech measures for the classification of MCI and AD.

Method: Individuals with MCI, mild-to-moderate AD and healthy controls (HCs) underwent a structural MRI scan and a battery of neuropsychological tests. They also engaged in a collaborative referencing task with a caregiver. The associations between the conversational speech timing features, cognitive function (domain-specific) and regional brain volumes were examined by means of linear mixed-effect modeling. Genetic programming was used to explore the discriminative ability of the conversational speech features.

Results: MCI and mild-to-moderate AD are characterized by a general slowness of speech, attributed to slower speech rate and slower turn-taking in conversational settings. The speech characteristics appear to be reflective of episodic, lexico-semantic, executive functioning and visuospatial deficits and underlying volume reductions in frontal, temporal and cerebellar areas.

Conclusion: The implementation of conversational speech timing-based technologies in clinical and community settings may provide additional markers for the early detection of cognitive deficits and structural changes associated with MCI and AD.
Suppression of Human Coronavirus 229E Infection in Lung Fibroblast Cells via RNA Interference
Authors: Montazeri Aliabadi Hamidreza , Totonchy Jennifer , Mahdipoor Parvin , Parang Keykavous , Uludağ Hasan
Published: April 2021

Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will result in lower viral load and reduced cell death. Two different categories of nucleic acid delivery systems, Peptide/Lipid-Associated Nucleic Acids (PLANAs) and lipophilic polymers, were investigated for their toxicity in human lung fibroblast cells and their ability to deliver specific siRNAs targeting Spike and Envelope proteins in order to prevent cell death in infected cells. Selected siRNAs were effectively delivered to human lung fibroblast cells with negligible toxicity. Cell death due to viral infection was significantly reduced with individual and combinatorial silencing of selected viral proteins. The combinatorial silencing of Spike and Envelope proteins restored the cell viability completely and eliminated plaques in the investigated system. Our cell culture data indicate promising results for the RNAi based approach as an alternative antiviral treatment.
Comparing the Clinical and Neuropsychological Characteristics of Parkinson’s Disease With and Without Freezing of Gait
Authors: Taximaimaiti Reyisha , Wang Xiao-Ping
Published: April 2021

Introduction

Freezing of gait (FOG) is one of the most common walking problems in Parkinson’s disease (PD). Impaired cognitive function is believed to play an important role in developing and aggravating FOG in PD. But some evidence suggests that motor function discrepancy may affect testing results. Therefore, we think it is necessary for PD-FOG(+) and PD-FOG(−) patients to complete neuropsychological tests under similar motor conditions.

Methods

This study recruited 44 idiopathic PD patients [PD-FOG(+) n = 22, PD-FOG(−) n = 22] and 20 age-matched healthy controls (HC). PD-FOG(+) and PD-FOG(−) patients were matched for age, year of education, and Hoehn and Yahr score (H&Y). All participants underwent a comprehensive battery of neuropsychological assessment, and demographical and clinical information was also collected.

Results

PD patients showed poorer cognitive function, higher risks of depression and anxiety, and more neuropsychiatric symptoms compared with HC. When controlling for age, years of education, and H&Y, there were no statistical differences in cognitive function between PD-FOG(+) and PD-FOG(−) patients. But PD-FOG(+) patients had worse motor and non-motor symptoms than PD-FOG(−) patients. PD patients whose motor symptoms initiated with rigidity and initiated unilaterally were more likely to experience FOG.

Conclusion

Traditional neuropsychological testing may not be sensitive enough to detect cognitive impairment in PD. Motor symptoms initiated with rigidity and initiated unilaterally might be an important predictor of FOG.
TERT-Promoter Mutational Status in Glioblastoma – Is There an Association With Amino Acid Uptake on Dynamic 18F-FET PET?
Authors: Unterrainer Marcus , Ruf Viktoria , von Rohr Katharina , Suchorska Bogdana , Mittlmeier Lena Maria , Beyer Leonie , Brendel Matthias , Wenter Vera , Kunz Wolfgang G. , Bartenstein Peter , Herms Jochen , Niyazi Maximilian , Tonn Jörg C. , Albert Nathalie Lisa
Published: April 2021

Objective

The mutation of the ‘telomerase reverse transcriptase gene promoter’ (TERTp) has been identified as an important factor for individual prognostication and tumorigenesis and will be implemented in upcoming glioma classifications. Uptake characteristics on dynamic 18F-FET PET have been shown to serve as additional imaging biomarker for prognosis. However, data on the correlation of TERTp-mutational status and amino acid uptake on dynamic 18F-FET PET are missing. Therefore, we aimed to analyze whether static and dynamic 18F-FET PET parameters are associated with the TERTp-mutational status in de-novo IDH-wildtype glioblastoma and whether a TERTp-mutation can be predicted by dynamic 18F-FET PET.

Methods

Patients with de-novo IDH-wildtype glioblastoma, WHO grade IV, available TERTp-mutational status and dynamic 18F-FET PET scan prior to any therapy were included. Here, established clinical parameters maximal and mean tumor-to-background-ratios (TBRmax/TBRmean), the biological-tumor-volume (BTV) and minimal-time-to-peak (TTPmin) on dynamic PET were analyzed and correlated with the TERTp-mutational status.

Results

One hundred IDH-wildtype glioblastoma patients were evaluated; 85/100 of the analyzed tumors showed a TERTp-mutation (C228T or C250T), 15/100 were classified as TERTp-wildtype. None of the static PET parameters was associated with the TERTp-mutational status (median TBRmax 3.41 vs. 3.32 (p=0.362), TBRmean 2.09 vs. 2.02 (p=0.349) and BTV 26.1 vs. 22.4 ml (p=0.377)). Also, the dynamic PET parameter TTPmin did not differ in both groups (12.5 vs. 12.5 min, p=0.411). Within the TERTp-mutant subgroups (i.e., C228T (n=23) & C250T (n=62)), the median TBRmax (3.33 vs. 3.69, p=0.095), TBRmean (2.08 vs. 2.09, p=0.352), BTV (25.4 vs. 30.0 ml, p=0.130) and TTPmin (12.5 vs. 12.5 min, p=0.190) were comparable, too.

Conclusion

Uptake characteristics on dynamic 18F-FET PET are not associated with the TERTp-mutational status in glioblastoma However, as both, dynamic 18F-FET PET parameters as well as the TERTp-mutation status are well-known prognostic biomarkers, future studies should investigate the complementary and independent prognostic value of both factors in order to further stratify patients into risk groups.
Characteristics of Ground-Glass Nodules Detected by Low-Dose Computed Tomography as a Regular Health Examination Among Chinese Hospital Employees and Their Parents
Authors: Ouyang Bihan , Li Maoyuan , Li Li , Liu Shaohui , Li Min
Published: April 2021

Introduction

Annual LDCT has been offered as a regular examination among many unit staff in China. Along with the wide application of LDCT, more and more ground-glass nodules were found. We focused on characteristics and relationship of ground-glass nodules detected by LDCT as a regular health examination among Chinese hospital employees and their parents.

Methods

We recorded LDCT-detected ground-glass nodules (GGNs) in the hospital employees and parents between 2019 and 2020. Clinical information, including age, gender, smoking status was collected and analyzed.

Results

A total of 5,574 employees and 2,686 employs’ parents ≥60 years in Xiangya hospital performed annual physical examination. In total, LDCT incidentally detected ground-glass nodules 392 (24.78%, 392/1,582) in hospital employees and 254 in parents (10.80%, 254/2,352). The GGN-detection rate was significantly greater in employee group than parent group and more non-smokers in former (P <0.001). The detection rate was significantly greater in female than male both in employees group and parents group, and the proportion of female was bigger in employees group (P <0.001). There were more pure-GGNs both in employees group and parents group. There were less participants with solitary GGN in employee group than parent group (P = 0.033). Besides, there were more large GGNs (≥10 mm) (P <0.001), LU-RADS 4 GGNs (P <0.001) and LU-RADS 4B GGNs (P = 0.003), LU-RADS 4C-5 GGNs (P = 0.001) in parent group than employee group. There were 36 employee–parent pairs (27.07%) both had GGNs among 133 pairs who both performed LDCT. GGNs in employees were smaller and lower-grade than their parents (P < 0.001, P = 0.001).

Conclusions

Among the employees and parents who had ground glass nodules, 1/4 of them both detected GGNs. Although the detection rate of GGNs in the parent group was lower than that in the employee group, the grade of nodules was significantly higher. All these suggest that the occurrence and development of ground glass nodules may be related to genetic factors.
Case Report: Cardiac Involvement by Lymphoma: Rare but Heterogeneous Condition With Challenging Behaviors
Authors: Lucchini Elisa , Merlo Marco , Ballerini Mario , Porcari Aldostefano , Sinagra Gianfranco , Pagnan Lorenzo , Rensi Marco , Romano Andrea , Bussani Rossana , Ballotta Laura , Zaja Francesco
Published: April 2021

Cardiac lymphomas are rare extranodal lymphomas involving primarily and secondarily the heart and/or pericardium. Here we describe three cases of cardiac involvement from lymphoma with specific peculiarities: two primary cardiac Diffuse Large B-cell Lymphomas and one secondary involvement from Marginal Zone Lymphoma (MZL). The first case highlights the issue of early CNS relapse and the possible role for CNS prophylaxis; the second case demonstrates the difficulties of interpretation and possible mistakes of different radiologic techniques adopted to evaluate cardiac involvement by lymphoma during follow-up; the third is a unique case of MZL with cardiac involvement. Our aim is to share the findings observed in these cases putting them in relation with data from the literature.
Effects of Fish Oil Supplementation on Cardiometabolic Risk Factors in Overweight or Obese Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials
Authors: Wu Shaojing , Zhu Chunhong , Wang Zhen , Wang Shumei , Yuan Pengfei , Song Tao , Hou Xiaoli , Lei Zhixian
Published: April 2021

Background: Influences of fish oil supplementation on body weight and other cardiometabolic factors in overweight or obese children and adolescents remain not fully understood. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of fish oil for these children.

Methods: Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model, which incorporates the potential heterogeneity of the included studies, was used to pool the results.

Results: Twelve RCTs including 1,028 overweight or obese children and adolescents were included. Compared to control, fish oil supplementation significantly reduced body mass index [BMI, mean difference (MD): −0.96 kg/m2, 95% confidence interval (CI): −1.69 to −0.23, P = 0.01] but did not significantly reduce body weight or waist circumference (P = 0.68 and 0.76). Moreover, fish oil supplementation significantly reduced serum triglyceride (MD: −0.24 mmol/L, 95% CI: −0.40 to −0.08, P = 0.004) but did not significantly affect serum total cholesterol and high-density or low-density lipoprotein cholesterol (P = 0.83, 0.42, and 0.31, respectively). Additionally, fish oil supplementation significantly lowered systolic blood pressure (SBP, MD: −2.46 mmHg, 95% CI: −4.93 to −0.01, P = 0.04) but did not significantly change diastolic blood pressure (P = 0.22). Supplementation with fish oil did not significantly affect fasting plasma glucose (P = 0.33).

Conclusions: In overweight or obese children and adolescents, supplementation with fish oil could reduce BMI, decrease serum triglyceride, and lower SBP, while serum cholesterol and fasting glucose may not be significantly affected.
Current Status and Trends in Peptide Receptor Radionuclide Therapy in the Past 20 Years (2000–2019): A Bibliometric Study
Authors: Lu Xiaojing , Lu Cuncun , Yang Yongjie , Shi Xiangfen , Wang Haibo , Yang Nan , Yang Kehu , Zhang Xiaojian
Published: April 2021

Background: Peptide receptor radionuclide therapy (PRRT) is an emerging therapeutic option for the treatment of neuroendocrine tumors (NETs), and the number of publications in this field has been increasing in recent years. The aim of the present study was to present the research status and summarize the key topics through bibliometric analysis of published PRRT literature.

Methods: A literature search for PRRT research from 2000 to 2019 was conducted using the Science Citation Index Expanded of Web of Science Core Collection (limited to SCIE) on August 4, 2020. The VOSviewer, R-bibliometrix, and CiteSpace software were used to conduct the bibliometric analysis.

Results: From 2000 to 2019, a total of 681 publications (523 articles and 158 reviews) were retrieved. Annual publication outputs grew from three to 111 records. Germany had the largest number of publications, making the largest contribution to the field (n = 151, 22.17%). Active cooperation between countries/regions was observed. Kwekkeboom from the Erasmus Medical Center is perhaps a key researcher in the field of PRRT. The European Journal of Nuclear Medicine and Molecular Imaging and Journal of Nuclear Medicine ranked first for productive (n = 84, 12.33%) and co-cited (n = 3,438) journals, respectively. Important topics mainly included matters related to the efficacy of PRRT (e.g., 90Y-dotatoc and 177Lu-dotatate), the long-term adverse effects of PRRT (e.g., hematologic and renal toxicities), standardization of NETs and PRRT in practice, the development of medical imaging techniques, and the individual dose optimization of PRRT.

Conclusion: Using bibliometric analysis, we gained deep insight into the global status and trends of studies investigating PRRT for the first time. The PRRT field is undergoing a period of rapid development, and our study provides a valuable reference for clinical researchers and practitioners.
Medication-Related Problems in Liver Transplant Recipients in the Outpatient Setting: A Dutch Cohort Study
Authors: Mulder Midas B. , Borgsteede Sander D. , Darwish Murad Sarwa , Landman Catelijne S. , Metselaar Herold J. , Hunfeld Nicole G.M.
Published: April 2021

Background: After liver transplantation (LTx), adherence to immunosuppressive medication and avoidance of contra-indicated drugs is essential for long-term survival. This study aimed to investigate the prevalence, types and severity of medication-related problems (MRPs) and interventions initiated by a clinical pharmacist (CP) in a cohort of LTx recipients in the outpatient setting.

Method: This study was a retrospective, observational study in LTx recipients that visited the outpatient clinic for an annual check-up. A 20-minutes consultation with a CP consisted of medication reconciliation and consultation about medication, adherence, and adverse drug reactions (ADRs). Discrepancies between actual and intended drug use, and MRPs were identified and the severity of MRPs was assessed. Potential interventions were discussed with the patient and the treating physician and evaluated after one year.

Results: The CP counseled 64 LTx recipients and found 96 discrepancies in 37 patients. Most discrepancies (60.4%, n = 58) concerned missing medications.

In total, 98 MRPs were identified in 53 patients (median 2; range 1-5 per patient), with a total of 113 interventions. Most frequent MRPs were: ADRs (22.4%, n = 22), nonadherence (19.3%, n = 19), unnecessary drugs (16.3%, n = 16) and undertreatment (12.2%, n = 12). Interventions most frequently proposed included optimization of dosage regimen (21.2%, n = 24), individualized recommendation regarding compliance (16.8%, n = 19) and drug discontinuation (12.4%, n = 14). After one year, 15 of the 19 patients (79%) experienced no longer compliance issues and 27 of the 29 patients (93%) used no drugs with indication issues anymore.

Conclusion: The CP in an outpatient monitoring program for LTx recipients can signal relevant discrepancies and MRPs. This leads to interventions that are accepted by both the patients and the physicians, with a positive effect after one year.
Interactions of Echinacea spp. Root Extracts and Alkylamides With the Endocannabinoid System and Peripheral Inflammatory Pain
Authors: Liu Rui , Caram-Salas Nadia L. , Li Wei , Wang Lili , Arnason John Thor , Harris Cory Steven
Published: April 2021

Historical ethnobotanies of indigenous peoples of the North American prairies reveal treatment of many painful conditions by Echinacea spp. Recent evidence suggests a pharmacological basis for such use as the bioactivity of E. angustifolia and E. purpurea is mediated, in part, through activation of the endocannabinoid system (ECS). Whereas the cannabimimetic effects of individual echinacea products and alkylamides have been described, the activity of crude extracts has not been compared between cannabinoid (CB) receptors or across species or genotypes. Moreover, few studies have explored echinacea’s engagement of the ECS for historic treatments or new therapeutic applications in peripheral inflammatory pain. We hypothesized that 1) the in vitro effects of root extracts on CB receptor internalization would vary with species and phytochemistry, and that echinacea root extracts would reduce inflammatory pain in vivo through activation of the ECS. Root extracts of different E. angustifolia and E. purpurea accessions were prepared, analyzed by HPLC-DAD to quantify caffeic acid derivatives and alkylamides (AKA), and tested for agonist and antagonist activities using receptor redistribution assays. Linear regression of activity relative to phytochemistry identified predictive compounds that were assessed individually in redistribution assays. Extracts were evaluated in the Hargreaves model of chronic inflammatory pain in rats with co-administration of selective CB1/2 antagonists to gauge involvement of the ECS. CB receptor agonist activity varied among accessions of both species with linear regression revealing a significant relationship between CB1 activity and AKA2 for E angustifolia, and AKA 9 + 10 for E purpurea. CB2 activity was positively related with AKA 9 + 10 and total AKAs in E. angustifolia. Four isolated AKA demonstrated agonist activity in the CB2, but not CB1, assay. In the inflammatory pain model, oral administration of either E angustifolia or E. purpurea root extract produced dose-dependent analgesic effects that were partially reversed by co-administration of CB receptor antagonists. This study demonstrates that in vitro effects of crude echinacea root extracts on CB receptors is predicted by phytochemistry. In vivo, echinacea has potential applications for peripheral inflammatory pain such as arthritis and burns, reflecting the traditional uses of Indigenous North Americans.
Cigarette Smoke Exposure, Pediatric Lung Disease, and COVID-19
Authors: Schiliro Marta , Vogel Elizabeth R. , Paolini Lucia , Pabelick Christina M.
Published: April 2021

The detrimental effects of tobacco exposure on children’s health are well known. Nonetheless, the prevalence of secondhand or direct cigarette smoke exposure (CSE) in the pediatric population has not significantly decreased over time. On the contrary, the rapid incline in use of e-cigarettes among adolescents has evoked public health concerns since increasing cases of vaping-induced acute lung injury have highlighted the potential harm of these new “smoking” devices. Two pediatric populations are especially vulnerable to the detrimental effects of cigarette smoke. The first group is former premature infants whose risk is elevated both due to their prematurity as well as other risk factors such as oxygen and mechanical ventilation to which they are disproportionately exposed. The second group is children and adolescents with chronic respiratory diseases, in particular asthma and other wheezing disorders. Coronavirus disease 2019 (COVID-19) is a spectrum of diseases caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has spread worldwide over the last year. Here, respiratory symptoms ranging from mild to acute respiratory distress syndrome (ARDS) are at the forefront of COVID-19 cases among adults, and cigarette smoking is associated with worse outcomes in this population, and cigarette smoking is associated with worse outcomes in this population. Interestingly, SARS-CoV-2 infection affects children differently in regard to infection susceptibility, disease manifestations, and complications. Although children carry and transmit the virus, the likelihood of symptomatic infection is low, and the rates of hospitalization and death are even lower when compared to the adult population. However, multisystem inflammatory syndrome is recognized as a serious consequence of SARS-CoV-2 infection in the pediatric population. In addition, recent data demonstrate specific clinical patterns in children infected with SARS-CoV-2 who develop multisystem inflammatory syndrome vs. severe COVID-19. In this review, we highlight the pulmonary effects of CSE in vulnerable pediatric populations in the context of the ongoing SARS-CoV-2 pandemic.