bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Identification, Expression Profile of the TIFY Gene Family in Brassica oleracea var. capitata, and Their Divergent Response to Various Pathogen Infections and Phytohormone Treatments
Authors: Liu Xing , Zhao Cunbao , Yang Limei , Zhang Yangyong , Wang Yong , Fang Zhiyuan , Lv Honghao
Published: January 2020

TIFY, a plant-specific gene family with the conserved motif TIF[F/Y]XG, plays important roles in various plant biological processes. Here, a total of 36 TIFY genes were identified in the Brassica oleracea genome and classified into JAZ (22 genes), TIFY (7 genes), ZML (5 genes), and PPD (2 genes) subfamilies based on their conserved motifs, which were distributed unevenly across nine chromosomes with different lengths (339–1077 bp) and exon numbers (1–8). Following phylogenetic analysis with A. thaliana and B. rapa TIFY proteins, ten clades were obtained. The expression of these TIFY genes was organ-specific, with thirteen JAZ genes and two PPD genes showing the highest expression in roots and leaves, respectively. More importantly, the JAZs showed divergent responses to various pathogen infections and different phytohormone treatments. Compared with the susceptible line, most JAZs were activated after Plasmodiophora brassicae infection, while there were both induced and inhibited JAZs after Fusarium oxysporum or Xanthomonas campestris infection in the resistance line, indicating their probably distinct roles in disease resistance or susceptibility. Further, the JAZs were all upregulated after MeJA treatment, but were mostly downregulated after SA/ET treatment. In summary, these results contribute to our understanding of the TIFY gene family, revealing that JAZs may play crucial and divergent roles in phytohormone crosstalk and plant defense.
Numerical Simulation of a Debris Flow on the Basis of a Two-Dimensional Continuum Body Model
Authors: Takebayashi Hiroshi , Fujita Masaharu
Published: January 2020

A two-dimensional debris and mud flow model that considers both laminar and turbulence flow was developed. Subsequently, the model was applied to a debris flow that occurred in Asaminami, Hiroshima, Japan in August 2014. The applicability of the model and the debris flow characteristics are discussed. The calculated horizontal distribution of sediment deposited in the Asaminami residential area was in good agreement with the horizontal distribution of the deposited large rocks and driftwood. This result indicates that the fine material in the downstream area was transported by water flow resulting from heavy rain that occurred after the debris flow. The scale of the initial debris flow was small; however, it increased with time, because eroded bed material and water were entrained to it. Therefore, it is important to reproduce the development process of debris flows to predict the amount of sediment produced, the deepest flow depth, the maximum flow velocity, and the inundation area. The averaged velocity of the simulated debris flow was about 9 m/s, and the velocity at the entrance to the residential area was about 8 m/s. This kind of information can be used to design sediment deposition dams. The travel time of the simulated debris flow from the upstream end of the main channel to the entrance of the residential area was 96 s. This kind of information can be used for making evacuation plans. Valley bed steps can suppress the deepest flow depth which is very important for the design of check dams; therefore, the high-resolution elevation data and fine numerical grids that reproduce step shapes are required to accurately calculate the deepest flow depth and maximum flow velocity.
Comprehensive Geriatric Assessment for Frail Older People in Swedish Acute Care Settings (CGA-Swed): A Randomised Controlled Study
Authors: Wilhelmson Katarina , Andersson Hammar Isabelle , Ehrenberg Anna , Niklasson Johan , Eckerblad Jeanette , Ekerstad Niklas , Westgård Theresa , Holmgren Eva , Åberg N. David , Dahlin Ivanoff Synneve
Published: January 2020

The aim of the study is to evaluate the effects of the Comprehensive Geriatric Assessment (CGA) for frail older people in Swedish acute hospital settings – the CGA-Swed study. In this study protocol, we present the study design, the intervention and the outcome measures as well as the baseline characteristics of the study participants. The study is a randomised controlled trial with an intervention group receiving the CGA and a control group receiving medical assessment without the CGA. Follow-ups were conducted after 1, 6 and 12 months, with dependence in activities of daily living (ADL) as the primary outcome measure. The study group consisted of frail older people (75 years and older) in need of acute medical hospital care. The study design, randomisation and process evaluation carried out were intended to ensure the quality of the study. Baseline data show that the randomisation was successful and that the sample included frail older people with high dependence in ADL and with a high comorbidity. The CGA contributed to early recognition of frail older people’s needs and ensured a care plan and follow-up. This study is expected to show positive effects on frail older people’s dependence in ADL, life satisfaction and satisfaction with health and social care.
Assessing Digital Soil Inventories for Predicting Streamflow in the Headwaters of the Blue Nile
Authors: Adem Anwar A. , Dile Yihun T. , Worqlul Abeyou W. , Ayana Essayas K. , Tilahun Seifu A. , Steenhuis Tammo S.
Published: January 2020

Comprehensive spatially referenced soil data are a crucial input in predicting biophysical and hydrological landscape processes. In most developing countries, these detailed soil data are not yet available. The objective of this study was, therefore, to evaluate the detail needed in soil resource inventories to predict the hydrologic response of watersheds. Using three distinctively different digital soil inventories, the widely used and tested soil and water assessment tool (SWAT) was selected to predict the discharge in two watersheds in the headwaters of the Blue Nile: the 1316 km2 Rib watershed and the nested 3.59 km2 Gomit watershed. The soil digital soil inventories employed were in increasing specificity: the global Food and Agricultural Organization (FAO), the Africa Soil Information Service (AfSIS) and the Amhara Design and Supervision Works Enterprise (ADSWE). Hydrologic simulations before model calibration were poor for all three soil inventories used as input. After model calibration, the streamflow predictions improved with monthly Nash–Sutcliffe efficiencies greater than 0.68. Predictions were statistically similar for the three soil databases justifying the use of the global FAO soil map in data-scarce regions for watershed discharge predictions.
Development and Investigation of a Wearable Aid for a Load Carriage Task
Authors: Alabdulkarim Saad A. , Farhan Abdulsalam M. , Ramadan Mohamed Z.
Published: January 2020

Anterior load carriage tasks are common and can lead to musculoskeletal disorders such as lower back pain. The objectives of this study were to develop a wearable carriage aid and examine its effectiveness on physical demands while considering the potential moderating influence of the carried load. The study consisted of two within-subject factors: device and load. For the former, two levels were tested: with and without the device worn. For the latter, two loads were examined: 15 and 30% of each individual’s body mass. Sixteen participants walked on a treadmill for five minutes at a constant speed for each condition. Physical demands were quantified using objective (EMG-based) and subjective (discomfort) measures. Wearing the device reduced static and median anterior deltoid, trapezius, and biceps brachii muscle activations. Increasing the carried load increased most physical demand measures. Two significant Device × Load interactions were observed; for the anterior deltoid and trapezius median activation measures, the influence of increasing load was lower when the device was worn. While slightly increasing perceived discomfort in the lower back, wearing the device reduced shoulder, neck, and hand/wrist discomfort. While the study demonstrated a potential for the device, future work is required under more realistic and diverse testing conditions.
The Impact of Dengue on Economic Growth: The Case of Southern Taiwan
Authors: Sher Chien-Yuan , Wong Ho Ting , Lin Yu-Chun
Published: January 2020

Dengue has long been a public health problem in tropical and subtropical countries. In 2015, a dengue outbreak occurred in Taiwan, where 43,784 cases were reported. This study aims to assess the impact of dengue on Southern Taiwan’s economic growth according to the economic growth model-based regression approach recommended by the World Health Organization (WHO). Herein, annual data from Southern Taiwan on the number of dengue cases, income growth, and demographics from 2010–2015 were analyzed. The percentage of reduction of the average income per capita in 2015 due to the dengue outbreak was estimated. Dengue was determined to have a negative linear economic impact on Southern Taiwan’s economic growth. In particular, a reduction of 0.26% in the average income per capita was estimated in Southern Taiwan due to the 2015 outbreak. If the model is applied alongside other dengue outbreak forecast models, then the forecast for economic reduction due to a future dengue outbreak may also be estimated. Prevention and recovery policies may subsequently be decided upon based on not only the number of dengue cases but also the degree of economic burden resulting from an outbreak.
Cross-Cultural Adaptation and Psychometric Testing of the International Sedentary Assessment Tool for the Spanish Population
Authors: Cuesta-Vargas Antonio I. , Roldán-Jiménez Cristina , Martín-Martín Jaime , González-Sánchez Manuel , Gutiérrez Sánchez Daniel
Published: January 2020

Sedentary behavior (SB) is currently considered a public health problem with a high cost of care. Evaluating SB is essential for prevention and early management of physical inactivity. The International Sedentary Assessment Tool (ISAT) is an instrument that has been developed to assess SB. The aim of this study was to carry out a cross-cultural adaptation and a psychometric analysis of the Spanish version of the ISAT. A cross-sectional study was conducted. A total of 432 participants were included in this study. A double forward method and a backward method were used to translate the ISAT. A psychometric analysis of internal consistency and concurrent criterion validity was performed according to the most up-to-date Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN). No language difficulties were found in the translation process. The Spanish version of ISAT was readable and acceptable. Internal consistency was satisfactory (α = 0.80). Criterion validity was demonstrated (rho=0.63). The Spanish version of the ISAT is a valid and reliable measure that can be used clinically to assess SB. Further studies assessing other psychometric properties are needed.
Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases
Authors: Subedi Lalita , Lee Si Eun , Madiha Syeda , Gaire Bhakta Prasad , Jin Mirim , Yumnam Silvia , Kim Sun Yeou
Published: January 2020

Tumor necrosis factor-alpha (TNF-α) is a well-known pro-inflammatory cytokine responsible for the modulation of the immune system. TNF-α plays a critical role in almost every type of inflammatory disorder, including central nervous system (CNS) diseases. Although TNF-α is a well-studied component of inflammatory responses, its functioning in diverse cell types is still unclear. TNF-α functions through its two main receptors: tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), also known as p55 and p75, respectively. Normally, the functions of soluble TNF-α-induced TNFR1 activation are reported to be pro-inflammatory and apoptotic. While TNF-α mediated TNFR2 activation has a dual role. Several synthetic drugs used as inhibitors of TNF-α for diverse inflammatory diseases possess serious adverse effects, which make patients and researchers turn their focus toward natural medicines, phytochemicals in particular. Phytochemicals targeting TNF-α can significantly improve disease conditions involving TNF-α with fewer side effects. Here, we reviewed known TNF-α inhibitors, as well as lately studied phytochemicals, with a role in inhibiting TNF-α itself, and TNF-α-mediated signaling in inflammatory diseases focusing mainly on CNS disorders.
The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis
Authors: Villalobo Antonio , Berchtold Martin W.
Published: January 2020

Calmodulin (CaM) is the principal Ca2+ sensor protein in all eukaryotic cells, that upon binding to target proteins transduces signals encoded by global or subcellular-specific changes of Ca2+ concentration within the cell. The Ca2+/CaM complex as well as Ca2+-free CaM modulate the activity of a vast number of enzymes, channels, signaling, adaptor and structural proteins, and hence the functionality of implicated signaling pathways, which control multiple cellular functions. A basic and important cellular function controlled by CaM in various ways is cell motility. Here we discuss the role of CaM-dependent systems involved in cell migration, tumor cell invasiveness, and metastasis development. Emphasis is given to phosphorylation/dephosphorylation events catalyzed by myosin light-chain kinase, CaM-dependent kinase-II, as well as other CaM-dependent kinases, and the CaM-dependent phosphatase calcineurin. In addition, the role of the CaM-regulated small GTPases Rac1 and Cdc42 (cell division cycle protein 42) as well as CaM-binding adaptor/scaffold proteins such as Grb7 (growth factor receptor bound protein 7), IQGAP (IQ motif containing GTPase activating protein) and AKAP12 (A kinase anchoring protein 12) will be reviewed. CaM-regulated mechanisms in cancer cells responsible for their greater migratory capacity compared to non-malignant cells, invasion of adjacent normal tissues and their systemic dissemination will be discussed, including closely linked processes such as the epithelial–mesenchymal transition and the activation of metalloproteases. This review covers as well the role of CaM in establishing metastatic foci in distant organs. Finally, the use of CaM antagonists and other blocking techniques to downregulate CaM-dependent systems aimed at preventing cancer cell invasiveness and metastasis development will be outlined.
Intracellular Calcium Dysregulation by the Alzheimer’s Disease-Linked Protein Presenilin 2
Authors: Galla Luisa , Redolfi Nelly , Pozzan Tullio , Pizzo Paola , Greotti Elisa
Published: January 2020

Alzheimer’s disease (AD) is the most common form of dementia. Even though most AD cases are sporadic, a small percentage is familial due to autosomal dominant mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes. AD mutations contribute to the generation of toxic amyloid β (Aβ) peptides and the formation of cerebral plaques, leading to the formulation of the amyloid cascade hypothesis for AD pathogenesis. Many drugs have been developed to inhibit this pathway but all these approaches currently failed, raising the need to find additional pathogenic mechanisms. Alterations in cellular calcium (Ca2+) signaling have also been reported as causative of neurodegeneration. Interestingly, Aβ peptides, mutated presenilin-1 (PS1), and presenilin-2 (PS2) variously lead to modifications in Ca2+ homeostasis. In this contribution, we focus on PS2, summarizing how AD-linked PS2 mutants alter multiple Ca2+ pathways and the functional consequences of this Ca2+ dysregulation in AD pathogenesis.
Transcriptome Analysis of Drought-Resistant and Drought-Sensitive Sorghum (Sorghum bicolor) Genotypes in Response to PEG-Induced Drought Stress
Authors: Abdel-Ghany Salah E. , Ullah Fahad , Ben-Hur Asa , Reddy Anireddy S. N.
Published: January 2020

Drought is a major limiting factor of crop yields. In response to drought, plants reprogram their gene expression, which ultimately regulates a multitude of biochemical and physiological processes. The timing of this reprogramming and the nature of the drought-regulated genes in different genotypes are thought to confer differential tolerance to drought stress. Sorghum is a highly drought-tolerant crop and has been increasingly used as a model cereal to identify genes that confer tolerance. Also, there is considerable natural variation in resistance to drought in different sorghum genotypes. Here, we evaluated drought resistance in four genotypes to polyethylene glycol (PEG)-induced drought stress at the seedling stage and performed transcriptome analysis in seedlings of sorghum genotypes that are either drought-resistant or drought-sensitive to identify drought-regulated changes in gene expression that are unique to drought-resistant genotypes of sorghum. Our analysis revealed that about 180 genes are differentially regulated in response to drought stress only in drought-resistant genotypes and most of these (over 70%) are up-regulated in response to drought. Among these, about 70 genes are novel with no known function and the remaining are transcription factors, signaling and stress-related proteins implicated in drought tolerance in other crops. This study revealed a set of drought-regulated genes, including many genes encoding uncharacterized proteins that are associated with drought tolerance at the seedling stage.
Clinical Implications of Estimating Glomerular Filtration Rate with Three Different Equations among Older People. Preliminary Results of the Project “Screening for Chronic Kidney Disease among Older People across Europe (SCOPE)”
Authors: Corsonello Andrea , Roller-Wirnsberger Regina , Wirnsberger Gerhard , Ärnlöv Johan , Carlsson Axel C. , Tap Lisanne , Mattace-Raso Francesco , Formiga Francesc , Moreno-Gonzalez Rafael , Weingart Christian , Sieber Cornel , Kostka Tomasz , Guligowska Agnieszka , Gil Pedro , Lainez Martinez Sara , Artzi-Medvedik Rada , Melzer Itshak , Lattanzio Fabrizia
Published: January 2020

We aimed at investigating to what extent CKD may be staged interchangeably by three different eGFR equations in older people, and evaluating the source of discrepancies among equations in a population of 2257 patients older than 75 years enrolled in a multicenter observational study. eGFR was calculated by CKD-EPI, BIS and FAS equations. Statistical analysis was carried out by Bland–Altman analysis. κ statistic was used to quantify the agreement between equations in classifying CKD stages. The impact of selected variables on the difference among equations was graphically explored. The average difference between BIS and FAS was −0.24 (95% limits of agreement (95%LA = −4.64–4.14) mL/min/1.73 m2. The difference between CKD-EPI and BIS and between CKD-EPI and FAS was 8.97 (95%LA = −2.90–20.84) and 8.72 (95%LA = −2.11–19.56) mL/min/1.73 m2, respectively. As regards CKD stage classification, κ value was 0.47 for both CKD-EPI vs. FAS and CKD-EPI vs. BIS, while BIS and FAS had similar classificatory properties (κ = 0.90). Muscle mass was found related to the difference between CKD-EPI and BIS (R2 = 0.11) or FAS (R2 = 0.14), but not to the difference between BIS and FAS. In conclusion, CKD-EPI and BIS/FAS equations are not interchangeable to assess eGFR among older people. Muscle mass may represent a relevant source of discrepancy among eGFR equations.
VEGFR2 Blockade Improves Renal Damage in an Experimental Model of Type 2 Diabetic Nephropathy
Authors: Lavoz Carolina , Rodrigues-Diez Raul R. , Plaza Anita , Carpio Daniel , Egido Jesús , Ruiz-Ortega Marta , Mezzano Sergio
Published: January 2020

The absence of optimal treatments for Diabetic Nephropathy (DN) highlights the importance of the search for novel therapeutic targets. The vascular endothelial growth factor receptor 2 (VEGFR2) pathway is activated in experimental and human DN, but the effects of its blockade in experimental models of DN is still controversial. Here, we test the effects of a therapeutic anti-VEGFR2 treatment, using a VEGFR2 kinase inhibitor, on the progression of renal damage in the BTBR ob/ob (leptin deficiency mutation) mice. This experimental diabetic model develops histological characteristics mimicking the key features of advanced human DN. A VEGFR2 pathway-activation blockade using the VEGFR2 kinase inhibitor SU5416, starting after kidney disease development, improves renal function, glomerular damage (mesangial matrix expansion and basement membrane thickening), tubulointerstitial inflammation and tubular atrophy, compared to untreated diabetic mice. The downstream mechanisms involved in these beneficial effects of VEGFR2 blockade include gene expression restoration of podocyte markers and downregulation of renal injury biomarkers and pro-inflammatory mediators. Several ligands can activate VEGFR2, including the canonical ligands VEGFs and GREMLIN. Activation of a GREMLIN/VEGFR2 pathway, but not other ligands, is correlated with renal damage progression in BTBR ob/ob diabetic mice. RNA sequencing analysis of GREMLIN-regulated genes confirm the modulation of proinflammatory genes and related-molecular pathways. Overall, these data show that a GREMLIN/VEGFR2 pathway activation is involved in diabetic kidney disease and could potentially be a novel therapeutic target in this clinical condition.
Predictors of Mental Health Outcomes in Road Traffic Accident Survivors
Authors: Kovacevic Jelena , Miskulin Maja , Degmecic Dunja , Vcev Aleksandar , Leovic Dinko , Sisljagic Vladimir , Simic Ivana , Palenkic Hrvoje , Vcev Ivan , Miskulin Ivan
Published: January 2020

Mental health outcomes of road traffic accidents (RTAs) are always investigated in assessments of those involved. The aim of this study was to investigate the psychological consequences and associated factors in all RTA survivors, irrelevant of their injury status. A cohort of 155 people was assessed one month after experiencing a RTA using self-reported measures for posttraumatic stress disorder (PTSD), depression, and anxiety. Associations between mental health outcomes and sociodemographic factors, pre-RTA health status, injury-related factors, and RTA details were analyzed. RTA survivors reported substantial rates of PTSD (32.3%) and depression (17.4%) symptoms, and low rates of anxiety (5.8%). Symptoms of depression were associated with below-average self-perceived economic status, irreligiousness, medication use, psychiatric medication use, and injury-related factors. PTSD symptoms were associated with female gender, below-average self-perceived economic status, previous psychiatric illness, medication use, psychiatric medication use, not being at fault in the relevant RTA, claiming compensation, and injury-related factors. Anxiety symptoms were associated with previous chronic or psychiatric illness, previous permanent pain, psychiatric medication use, and self-perceived threat to life, but not with sustaining injury. Along with the evaluation and treatment of RTA injuries, health care providers should evaluate the pre-RTA health status of all RTA victims. Psychological support to those at risk may prevent psychological disorders after RTAs.
Skin Cutibacterium acnes Mediates Fermentation to Suppress the Calcium Phosphate-Induced Itching: A Butyric Acid Derivative with Potential for Uremic Pruritus
Authors: Keshari Sunita , Wang Yanhan , Herr Deron Raymond , Wang Sung-Min , Yang Wu-Chang , Chuang Tsung-Hsien , Chen Chien-Lung , Huang Chun-Ming
Published: January 2020

Pruritus and inflammation associated with accumulation of calcium phosphate (CaP) under the skin are common problems among dialysis patients with chronic kidney disease (CKD). The role of skin commensal microbiota in the CaP-induced uremic pruritus remains uncharacterized. Skin Cutibacterium acnes (C. acnes) can solubilize CaP by the production of short-chain fatty acids (SCFAs), such as butyric acid, through glucose fermentation. Like butyric acid, the N-[2-(2-Butyrylamino-ethoxy)-ethyl]-butyramide (BA-NH-NH-BA), a butyric acid derivative, remarkably induced acetylation of histone H3 lysine 9 (AcH3K9) in keratinocytes. Topical application of fermenting C. acnes, butyric acid or BA-NH-NH-BA onto mouse skin effectively ameliorated CaP-induced skin itching, interleukin (IL)-6 up-regulation in keratinocytes, and extracellular signal-regulated kinase (ERK) 1/2 activation in dorsal root ganglia (DRG). Activation of ERK 1/2 by CaP was markedly reduced in IL-6 knockout mice. Genus Cutibacterium was detected in relatively low abundance in itchy skin of patients with CKD. Our results identify a role for the skin fermenting C. acnes in ameliorating CaP-induced activation of IL-6/p-ERK signaling and resulting skin inflammation. Furthermore, we provide evidence for the potential therapeutic efficacy of BA-NH-NH-BA as a postbiotic for the treatment of uremic pruritus.
Impact of Grape Products on Lipid Profile: A Meta-Analysis of Randomized Controlled Studies
Authors: Lupoli Roberta , Ciciola Paola , Costabile Giuseppina , Giacco Rosalba , Di Minno Matteo Nicola Dario , Capaldo Brunella
Published: January 2020

Background: Growing evidence shows that grape polyphenols can improve cardiovascular risk factors. Although there are clear data supporting a beneficial effect of grape supplementation on blood pressure and glucose metabolism, the effects of grape polyphenols on lipid metabolism are still controversial. Objective: We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of grape products on lipid profile. Design: A systematic search was performed in the PubMed, Web of Science, Scopus, and EMBASE databases without any language or publication year restriction. The reference lists of all retrieved articles were manually reviewed. RCTs evaluating the impact of grape products/juice/extracts on lipid profile were included. Difference in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), oxidized low-density lipoprotein cholesterol (oxLDL-C), apolipoprotein (apo) A, apo B before and after administration of grape products or placebo were expressed as mean differences (MD) with pertinent 95% confidence intervals (95% CI). The impact of clinical and demographic features on effect size was assessed by meta-regression. Results: The administration of grape products is associated with a significant improvement of lipid profile, as evidenced by changes in TC (MD: −7.6 mg/dL (−0.2 mmol/L); 95% CI: −10.8, −4.4; p < 0.001), HDL-C (MD: 1.4 mg/dL (0.04 mmol/L); 95% CI: 0.8, 1.9; p < 0.001, I2 = 74.7%, p < 0.001), LDL-C (−6.3 mg/dL (−0.16 mmol/L); 95% CI: −9.5, −3.0; p < 0.001), oxLDL-C (MD: −4.5 U/L; 95% CI: −7.5, −1.5; p = 0.003, I2 = 90.6%, p < 0.001), apo B (MD: −2.4 mg/dL (−0.05 µmol/L); 95% CI: −4.5, −0.3; p = 0.026), and TG (MD: −14.5 mg/dL (−0.16 mmol/L); 95% CI: −17.7, −11.2; p < 0.001) levels in subjects receiving grape products compared to placebo. With regard to the extent of the lipid-lowering effect, compared to baseline values, the highest reduction was reported for LDL-C (MD: −5.6 mg/dL (−0.14 mmol/L); 95% CI: −9.5, −1.7; p = 0.005) and for oxLDL-C (MD: −5.0 U/L; 95% CI: −8.8, −1.2; p = 0.010, I2 = 0%, p = 0.470). Conclusions: Grape polyphenols exert a favorable effect on lipid profile in humans by significantly reducing plasma levels of LDL-C and oxLDL-C.
Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
Authors: Sandlers Yana , Shah Rohan R. , Pearce Ryan W. , Dasarathy Jaividhya , McCullough Arthur J. , Dasarathy Srinivasan
Published: January 2020

Nonalcoholic liver disease (NAFLD) is manifested with a wide spectrum of clinical symptoms and is closely associated with the metabolic syndrome, inflammation, and mitochondrial dysfunction. Although the mechanism of mitochondrial dysfunction in NAFLD is still not fully elucidated, multiple studies have demonstrated evidence of molecular, biochemical, and biophysical mitochondrial abnormalities in NAFLD. Given the association between NAFLD and mitochondrial dysfunction, the aim of this study is to analyze circulating levels of Krebs cycle intermediates in a cohort of NAFLD-affected individuals and matching healthy controls and to correlate our findings with the liver function metrics. Standard serum biochemistry and Krebs cycle intermediates were analyzed in NAFLD (n = 22) and matched control (n = 67) cohorts. Circulating levels of isocitrate and citrate were significantly (p < 0.05) elevated in the NAFLD cohort of patients. The area under the curve (AUROC) for these two metabolites exhibited a moderate clinical utility. Correlations between plasma Krebs cycle intermediates and standard clinical plasma metrics were explored by Pearson’s correlation coefficient. The data obtained for plasma Krebs cycle intermediates suggest pathophysiological insights that link mitochondrial dysfunction with NAFLD. Our findings reveal that plasma isocitrate and citrate can discriminate between normal and NAFLD cohorts and can be utilized as noninvasive markers of mitochondrial dysfunction in NAFLD. Future studies with large populations at different NAFLD stages are warranted.
Simultaneously Improved Pulmonary and Cardiovascular Autonomic Function and Short-Term Functional Outcomes in Patients with Parkinson’s Disease after Respiratory Muscle Training
Authors: Huang Chih-Cheng , Lai Yun-Ru , Wu Fu-An , Kuo Nai-Ying , Tsai Yuh-Chyn , Cheng Ben-Chung , Tsai Nai-Wen , Lu Cheng-Hsien
Published: January 2020

Both pulmonary function and autonomic function are impaired in patients with Parkinson’s diseases (PD). This study tested the hypothesis that respiratory muscle training (RMT) can not only improve pulmonary function, but also simultaneously improve cardiovascular autonomic function and short-term functional outcomes in patients with PD. Pulmonary function was measured by the forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum inspiratory pressures (MIP), and maximum expiratory pressures (MEP). Cardiovascular autonomic function was measured by the heart rate response to deep breathing (HRDB), Valsalva ratio, baroreflex sensitivity, and spectral analysis. The functional and severity scores were measured by the Hoehn and Yahr stage and Unified Parkinson’s Disease Rating Scale (UPDRS). These measures were evaluated in patients with PD before and after 3 months of RMT, compared with a control group of PD patients without RMT. The results showed significant improvement of clinical scores (total UPDRS and UPDRS I, II and III) after RMT (p < 0.0001). Concerning pulmonary function, the parameters of MIP and MEP improved significantly. The parameters of cardiovascular function also improved after RMT, although only HRDB reached statistical significance. Based on the results of our study, RMT can not only improve both pulmonary and cardiovascular autonomic function, but can also improve short-term functional outcomes in patients with PD.
Role of Arginase 2 in Murine Retinopathy Associated with Western Diet-Induced Obesity
Authors: Atawia Reem T. , Bunch Katharine L. , Fouda Abdelrahman Y. , Lemtalsi Tahira , Eldahshan Wael , Xu Zhimin , Saul Alan , Elmasry Khaled , Al-Shabrawey Mohamed , Caldwell Ruth B. , Caldwell R. William
Published: January 2020

Western diet-induced obesity is linked to the development of metabolic dysfunctions, including type 2 diabetes and complications that include retinopathy, a leading cause of blindness. Aberrant activation of the inflammasome cascade leads to the progression of obesity-induced pathologies. Our lab showed the critical role of arginase 2 (A2), the mitochondrial isoform of this ureahydrolase, in obesity-induced metabolic dysfunction and inflammation. A2 deletion also has been shown to be protective against retinal inflammation in models of ischemic retinopathy and multiple sclerosis. We investigated the effect of A2 deletion on western diet-induced retinopathy. Wild-type mice fed a high-fat, high-sucrose western diet for 16 weeks exhibited elevated retinal expression of A2, markers of the inflammasome pathway, oxidative stress, and activation of microglia/macrophages. Western diet feeding induced exaggerated retinal light responses without affecting visual acuity or retinal morphology. These effects were reduced or absent in mice with global A2 deletion. Exposure of retinal endothelial cells to palmitate and high glucose, a mimic of the obese state, increased expression of A2 and inflammatory mediators and induced cell death. These effects, except for A2, were prevented by pretreatment with an arginase inhibitor. Collectively, our study demonstrated a substantial role of A2 in early manifestations of diabetic retinopathy.
Nanosystems for Improved Targeted Therapies in Melanoma
Authors: Beiu Cristina , Giurcaneanu Calin , Grumezescu Alexandru Mihai , Holban Alina Maria , Popa Liliana Gabriela , Mihai Mara Mădălina
Published: January 2020

Melanoma is one of the most aggressive forms of skin cancer, with limited therapeutic options. Since its incidence has been rapidly rising in recent years, the study of new targeted therapeutic strategies has increased. The implication of nanoscience in the development of alternative targeted therapies for melanoma has multiple benefits and could significantly improve the outcome of melanoma patients. In this paper, we review the most recent progress in the field of targeted therapies, emphasizing the impact of nanoscale materials on the targeting and controlled release of anti-tumor drugs. The applications of nanomedicine in the management of melanoma are extensive and refer to sentinel lymph node mapping, chemotherapy, and RNA interference; each of these applications harboring the potential to develop efficient and personalized diagnostic techniques and therapies. Further research, especially in clinical trials, is needed to establish whether fighting melanoma on the nanoscale level represents the key to reaching a critical inflection point in mankind’s battle with metastatic melanoma.
Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index
Authors: Garcia Erwin , Shalaurova Irina , Matyus Steven P. , Oskardmay David N. , Otvos James D. , Dullaart Robin P.F. , Connelly Margery A.
Published: January 2020

Background: Quantifying mildly elevated ketone bodies is clinically and pathophysiologically relevant, especially in the context of disease states as well as for monitoring of various diets and exercise regimens. As an alternative assay for measuring ketone bodies in the clinical laboratory, a nuclear magnetic resonance (NMR) spectroscopy-based test was developed for quantification of β-hydroxybutyrate (β-HB), acetoacetate (AcAc) and acetone. Methods: The ketone body assay was evaluated for precision, linearity and stability and method comparisons were performed. In addition, plasma ketone bodies were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1198; 373 type 2 diabetes mellitus (T2DM) subjects). Results: β-HB and AcAc quantified using NMR and mass spectrometry and acetone quantified using NMR and gas chromatography/mass spectrometry were highly correlated (R2 = 0.996, 0.994, and 0.994 for β-HB, AcAc, acetone, respectively). Coefficients of variation (%CVs) for intra- and inter-assay precision ranged from 1.3% to 9.3%, 3.1% to 7.7%, and 3.8% to 9.1%, for β-HB, AcAc and acetone, respectively. In the IRAS, ketone bodies were elevated in subjects with T2DM versus non-diabetic individuals (p = 0.011 to ≤0.001). Age- and sex-adjusted multivariable linear regression analysis revealed that total ketone bodies and β-HB were associated directly with free fatty acids (FFAs) and T2DM and inversely with triglycerides and insulin resistance as measured by the Lipoprotein Insulin Resistance Index. Conclusions: Concentrations of the three main ketone bodies can be determined by NMR with good clinical performance, are elevated in T2DM and are inversely associated with triglycerides and insulin resistance.
Impact of Using Different Levels of Threshold-Based Artefact Correction on the Quantification of Heart Rate Variability in Three Independent Human Cohorts
Authors: Alcantara Juan M. A. , Plaza-Florido Abel , Amaro-Gahete Francisco J. , Acosta Francisco M. , Migueles Jairo H. , Molina-Garcia Pablo , Sacha Jerzy , Sanchez-Delgado Guillermo , Martinez-Tellez Borja
Published: January 2020

Heart rate variability (HRV) is a non-invasive indicator of autonomic nervous system function. HRV recordings show artefacts due to technical and/or biological issues. The Kubios software is one of the most used software to process HRV recordings, offering different levels of threshold-based artefact correction (i.e., Kubios filters). The aim of the study was to analyze the impact of different Kubios filters on the quantification of HRV derived parameters from short-term recordings in three independent human cohorts. A total of 312 participants were included: 107 children with overweight/obesity (10.0 ± 1.1 years, 58% men), 132 young adults (22.2 ± 2.2 years, 33% men) and 73 middle-aged adults (53.6 ± 5.2 years, 48% men). HRV was assessed using a heart rate monitor during 10–15 min, and the Kubios software was used for HRV data processing using all the Kubios filters available (i.e., 6). Repeated-measures analysis of variance indicated significant differences in HRV derived parameters in the time-domain (all p < 0.001) across the Kubios filters in all cohorts, moreover similar results were observed in the frequency-domain. When comparing two extreme Kubios filters, these statistical differences could be clinically relevant, e.g. more than 10 ms in the standard deviation of all normal R-R intervals (SDNN). In conclusion, the results of the present study suggest that the application of different Kubios filters had a significant impact on HRV derived parameters obtained from short-term recordings in both time and frequency-domains.
Preclinical and Clinical Evidence of Immune Responses Triggered in Oncologic Photodynamic Therapy: Clinical Recommendations
Authors: Beltrán Hernández Irati , Yu Yingxin , Ossendorp Ferry , Korbelik Mladen , Oliveira Sabrina
Published: January 2020

Photodynamic therapy (PDT) is an anticancer strategy utilizing light-mediated activation of a photosensitizer (PS) which has accumulated in tumor and/or surrounding vasculature. Upon activation, the PS mediates tumor destruction through the generation of reactive oxygen species and tumor-associated vasculature damage, generally resulting in high tumor cure rates. In addition, a PDT-induced immune response against the tumor has been documented in several studies. However, some contradictory results have been reported as well. With the aim of improving the understanding and awareness of the immunological events triggered by PDT, this review focuses on the immunological effects post-PDT, described in preclinical and clinical studies. The reviewed preclinical evidence indicates that PDT is able to elicit a local inflammatory response in the treated site, which can develop into systemic antitumor immunity, providing long-term tumor growth control. Nevertheless, this aspect of PDT has barely been explored in clinical studies. It is clear that further understanding of these events can impact the design of more potent PDT treatments. Based on the available preclinical knowledge, recommendations are given to guide future clinical research to gain valuable information on the immune response induced by PDT. Such insights directly obtained from cancer patients can only improve the success of PDT treatment, either alone or in combination with immunomodulatory approaches.
Transdiagnostic or Disorder Specific? Indicators of Substance and Behavioral Addictions Nominated by People with Lived Experience
Authors: Kim Hyoun S. , Hodgins David C. , Kim Benjamin , Wild T. Cameron
Published: January 2020

Using a transdiagnostic perspective, the present research examined the prominent indicators of substance (alcohol, cocaine, marijuana, tobacco) and behavioral (gambling, video games, sex, shopping, work, eating) addictions nominated by people with lived experiences. Specifically, we aimed to explore whether the perceived most important indicators nominated were consistent across the 10 addictions or differed based on the specific addiction. Additionally, we explored gender differences in the perceived most important indicators across addictive behaviors. A large online sample of adults recruited from a Canadian province (n = 3503) were asked to describe the most important signs or symptoms of problems with these substances and behaviors. Open-ended responses were analyzed among a subsample of 2603 respondents (n = 1562 in the past year) who disclosed that they had personally experienced a problem with at least one addiction listed above. Content analyses revealed that dependence (e.g., craving, impairments in control) and patterns of use (e.g., frequency) were the most commonly perceived indicators for both substance and behavioral addictions, accounting for over half of all the qualitative responses. Differences were also found between substance and behavioral addictions regarding the proportion of the most important signs nominated. Consistent with the syndrome model of addiction, unique indicators were also found for specific addictive behaviors, with the greatest proportion of unique indicators found for eating. Supplemental analyses found that perceived indicators across addictions were generally gender invariant. Results provide some support for a transdiagnostic conceptualization of substance and behavioral addictions. Implications for the study, prevention, and treatment of addictions are discussed.
Acknowledgement to Reviewers of Journal of Low Power Electronics and Applications in 2019
Authors:   Journal Of Low Power Electronics And Applications Editorial Office
Published: January 2020

The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...]
Entropy-Stabilized Oxides owning Fluorite Structure obtained by Hydrothermal Treatment
Authors: Spiridigliozzi Luca , Ferone Claudio , Cioffi Raffaele , Accardo Grazia , Frattini Domenico , Dell’Agli Gianfranco
Published: January 2020

Entropy-Stabilized Oxides (ESO) is a modern class of multicomponent advanced ceramic materials with attractive functional properties. Through a five-component oxide formulation, the configurational entropy is used to drive the phase stabilization over a reversible solid-state transformation from a multiphase to a single-phase state. In this paper, a new transition metal/rare earth entropy-stabilized oxide, with composition Ce0.2Zr0.2Y0.2Gd0.2La0.2O2−δ, was found after several investigations on alternative candidate systems. X-Ray Diffraction (XRD) analyses of calcined powders pointed out different behavior as a function of the composition and a single-phase fluorite structure was obtained after a specific thermal treatment at 1500 °C. Powders presented the absence of agglomeration, so that the sintered specimen exhibited sufficient densification with a small porosity, uniformly distributed in the sample.
Submicron-Sized Nb-Doped Lithium Garnet for High Ionic Conductivity Solid Electrolyte and Performance of Quasi-Solid-State Lithium Battery
Authors: Ji Yan , Zhou Cankai , Lin Feng , Li Bingjing , Yang Feifan , Zhu Huali , Duan Junfei , Chen Zhaoyong
Published: January 2020

The garnet Li7La3Zr2O12 (LLZO) has been widely investigated because of its high conductivity, wide electrochemical window, and chemical stability with regards to lithium metal. However, the usual preparation process of LLZO requires high-temperature sintering for a long time and a lot of mother powder to compensate for lithium evaporation. In this study submicron Li6.6La3Zr1.6Nb0.4O12 (LLZNO) powder―which has a stable cubic phase and high sintering activity―was prepared using the conventional solid-state reaction and the attrition milling process, and Li stoichiometric LLZNO ceramics were obtained by sintering this powder―which is difficult to control under high sintering temperatures and when sintered for a long time―at a relatively low temperature or for a short amount of time. The particle-size distribution, phase structure, microstructure, distribution of elements, total ionic conductivity, relative density, and activation energy of the submicron LLZNO powder and the LLZNO ceramics were tested and analyzed using laser diffraction particle-size analyzer (LD), X-Ray Diffraction (XRD), Scanning Electron Microscope (SEM), Electrochemical Impedance Spectroscopy (EIS), and the Archimedean method. The total ionic conductivity of samples sintered at 1200 °C for 30 min was 5.09 × 10−4 S·cm−1, the activation energy was 0.311 eV, and the relative density was 87.3%. When the samples were sintered at 1150 °C for 60 min the total ionic conductivity was 3.49 × 10−4 S·cm−1, the activation energy was 0.316 eV, and the relative density was 90.4%. At the same time, quasi-solid-state batteries were assembled with LiMn2O4 as the positive electrode and submicron LLZNO powder as the solid-state electrolyte. After 50 cycles, the discharge specific capacity was 105.5 mAh/g and the columbic efficiency was above 95%.
Fracture Resistance of Zirconia Oral Implants In Vitro: A Systematic Review and Meta-Analysis
Authors: Bethke Annalena , Pieralli Stefano , Kohal Ralf-Joachim , Burkhardt Felix , von Stein-Lausnitz Manja , Vach Kirstin , Spies Benedikt Christopher
Published: January 2020

Various protocols are available to preclinically assess the fracture resistance of zirconia oral implants. The objective of the present review was to determine the impact of different treatments (dynamic loading, hydrothermal aging) and implant features (e.g., material, design or manufacturing) on the fracture resistance of zirconia implants. An electronic screening of two databases (MEDLINE/Pubmed, Embase) was performed. Investigations including > 5 screw-shaped implants providing information to calculate the bending moment at the time point of static loading to fracture were considered. Data was extracted and meta-analyses were conducted using multilevel mixed-effects generalized linear models (GLMs). The Šidák method was used to correct for multiple testing. The initial search resulted in 1864 articles, and finally 19 investigations loading 731 zirconia implants to fracture were analyzed. In general, fracture resistance was affected by the implant design (1-piece > 2-piece, p = 0.004), material (alumina-toughened zirconia/ATZ > yttria-stabilized tetragonal zirconia polycrystal/Y-TZP, p = 0.002) and abutment preparation (untouched > modified/grinded, p < 0.001). In case of 2-piece implants, the amount of dynamic loading cycles prior to static loading (p < 0.001) or anatomical crown supply (p < 0.001) negatively affected the outcome. No impact was found for hydrothermal aging. Heterogeneous findings of the present review highlight the importance of thoroughly and individually evaluating the fracture resistance of every zirconia implant system prior to market release.