bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabinoids in the Older Person: A Literature Review
Authors: Beedham William , Sbai Magda , Allison Isabel , Coary Roisin , Shipway David
Published: January 2020

Introduction: Medical cannabinoids have received significant mainstream media attention in recent times due to an evolving political and clinical landscape. Whilst the efficacy of cannabinoids in the treatment of some childhood epilepsy syndromes is increasingly recognized, medical cannabinoids may also have potential clinical roles in the treatment of older adults. Prescribing restrictions for medical cannabinoids in certain jurisdictions (including the UK) has recently been relaxed. However, few geriatricians have the detailed knowledge or awareness of the potential risks or rewards of utilizing cannabinoids in the older person; even fewer geriatricians have direct experience of using these drugs in their own clinical practice. Older persons are more likely to suffer from medical illness representing potential indications for medical cannabinoids (e.g., pain); equally they may be more vulnerable to any adverse effects. Aim: This narrative literature review aims to provide a brief introduction for the geriatrician to the potential indications, evidence-base, contra-indications and side effects of medical cannabinoids in older people. Methods: A search was conducted of CENTRAL, Medline, Embase, CINAHL and psycINFO, Cochrane and Web of Science databases. Reference lists were hand searched. Abstracts and titles were screened, followed by a full text reading of relevant articles. Results: 35 studies were identified as relevant for this narrative review. Conclusions: Cannabinoids demonstrate some efficacy in the treatment of pain and chemotherapy-related nausea; limited data suggest potential benefits in the treatment of spasticity and anxiety. Risks of cannabinoids in older patients appear to be moderate, and their frequency comparable to other analgesic drug classes. However, the quality of research is weak, and few older patients have been enrolled in cannabinoid studies. Dedicated research is needed to determine the efficiency and safety of cannabinoids in older patients.
Self-Reported General Health, Overall and Work-Related Stress, Loneliness, and Sleeping Problems in 335,625 Swedish Adults from 2000 to 2016
Authors: Blom Victoria , Kallings Lena V. , Ekblom Björn , Wallin Peter , Andersson Gunnar , Hemmingsson Erik , Ekblom Örjan , Söderling Jonas , Ekblom Bak Elin
Published: January 2020

The prevalence of poor health, in particular stress-related mental ill-health, is increasing over time and birth cohorts. As rapid societal changes have occurred in the last decade and still are occurring, there is an interest in investigating the trends in health-related factors. The aim of the present study was to investigate trends in self-reported general health, overall stress, work-related stress, feelings of loneliness, and sleeping problems in 335,625 Swedish adults across categories of gender, geographic regions, length of education, and age from 2000 to 2016. On population level, sleeping problems and poor general health have increased markedly and significantly, while experiences of work stress decreased between 2000 and 2016 (p < 0.05). Overall stress and level of loneliness were unchanged (p > 0.05). The risk of having ≥3 symptoms (any of poor or very poor general health, often or very often perceived overall stress, loneliness, or sleeping problems) has increased significantly from 2000 to 2016 (ß = 1034 (1027–1040)). This increase was significantly higher in young (ß = 1052 (1038–1065)) and individuals with lower education (ß = 1056 (1037–1076)) compared to older and high length of education.
Response to Buonocore et al. Comments on Wendt Hess et al. “Assessing Agreement in Exposure Classification between Proximity-Based Metrics and Air Monitoring Data in Epidemiology Studies of Unconventional Resource Development.” Int. J. Environ. Res. Public Health 2019, 16, 3055
Authors: Hess Judy Wendt , Bachler Gerald , Momin Fayaz , Sexton Krystal
Published: January 2020

We appreciate the comments by Buonocore et al [...]
Effect of the Modification of the Number of Players, the Size of the Goal, and the Size of the Field in Competition on the Play Actions in U-12 Male Football
Authors: García-Angulo Antonio , Palao José Manuel , Giménez-Egido José María , García-Angulo Francisco Javier , Ortega-Toro Enrique
Published: January 2020

A player’s sports development involves a long process. The modification of rules for youth players seeks to adapt the sport to the child and his/her development. The manipulation of rules affects the technical and tactical skills demonstrated by players and, therefore, their development. The objective of this study was to analyse the effect of a reduction in the number of players (from 8 per team to 5 per team), the size of the goal (from 6 × 2 m to 3 × 2 m) and the playing space (from 58 × 38 m to 38 × 20 m), on the technical and tactical actions in youth football players. A quasi-experimental A-B-A design was implemented to assess the effect of the rule changes. The players (n = 40) played three tournaments using two competition formats (official rules, modified rules, and official rules). The results show that the use of the modified rules generated a greater number and variability in the technical–tactical actions, a greater number of actions with teammates in the pass line, a greater continuity in the game, a greater number of attack and defence actions in areas close to the goal, and favours team play. The experimental format fits the players’ individual progression better (U-12) as well as the players’ and teams’ collective development, and it will allow players to evolve from the individual development of previous stages.
E-Cigarette Use by Smoking Status in Estonia, 2012–2018
Authors: Reile Rainer , Pärna Kersti
Published: January 2020

Background: In the context of declining smoking rates in Estonia, this study aims to analyze the recent trends in e-cigarette use and its associations with smoking status and sociodemographic factors. Methods: Nationally representative data from biennial cross-sectional health surveys in 2012–2018 (n = 9988) were used to describe the prevalence of smoking and e-cigarette use by smoking status in Estonia. Multivariate logistic regression analysis was used to describe the sociodemographic patterns of e-cigarette use in three subgroups: the general population, smokers, and ex-smokers. Results: The prevalence of current smoking decreased from 45.4% in 2012 to 31.5% in 2018 among men and from 26.6% to 20.0% among women. At the same time, e-cigarette use in the general population had increased to 3.7% among men and to 1.2% among women. The increase in the prevalence of e-cigarette use was statistically significant among men in the general population, smokers, and ex-smokers, but non-significant among women. In addition to period effects, e-cigarette use was patterned by age, gender, and education. Conclusion: In 2002–2018, the e-cigarette use had increased but smoking had decreased in Estonia. A timely and targeted tobacco policy may alleviate the harm of e-cigarette use from the public health perspective.
Effect of Aerobic Physical Activity on Health-Related Quality of Life in Middle Aged Women with Osteoarthritis: Korea National Health and Nutrition Examination Survey (2016–2017)
Authors: Ryu Mikyung , Lee Sol , Kim Ho , Baek Weon-Chil , Kimm Heejin
Published: January 2020

Background: There have been few studies reporting the association between health-related quality of life (HRQoL) and osteoarthritis (OA) in female subjects performing aerobic exercise or not. The aim of this study is to compare HRQoL between OA patients and non-OA subjects in middle aged Korean women (40–59 years) with/without aerobic physical activity, and also to identify an association between EQ-5D instrument based HRQoL and OA controlling for aerobic exercise. Methods: This study used the cross-sectional data, the Korea National Health and Nutrition Examination Survey (KNANES) from 2016 to 2017. We only selected those who had completed the evaluations of aerobic physical activity and osteoarthritis diagnosis. In total, 2445 middle aged women were finally selected for this study. The European quality of life-5 dimensions (EQ-5D) was used for the evaluation of HRQoL as a dependent variable. In socio-demographic factors, age, sex, income level, education level, marital status, economic activity, type of insurance and private insurance and behaviour-related factors were included. One-way analysis of variance was conducted to compare the EQ-5D index and multiple linear regression analysis was employed to identify associated factors with the EQ-5D index. Results: In total, 2445 middle aged women were included in this study, in which 2209 participants were normal (90.0%) with aerobic physical activity (no: 55.0%, yes: 45.0%) and 246 participants were diagnosed with osteoarthritis (10.0%) with aerobic physical activity (no: 56.1%, yes: 43.9%). In group 2-2 (OA with aerobic), the moderate level of muscle exercise (less than 5 days per week) showed the highest HRQoL (p < 0.05) and high level exercise showed the lowest HRQoL (p < 0.05). In menopause status, the participants under menopause status showed lower HRQoL (p < 0.05) than those not under menopause status in group 2-2 (OA with aerobic) only. Conclusions: The HRQoL of OA patients was significantly lower than that of normal participants in middle aged Korean women (40–59 years). Especially, OA patients with maintained aerobic physical activity showed significantly higher HRQoL than those without that under controlling covariates such as age, income level, education level, marital status, economic activity, type of insurance, etc.
Multidimensional Self-Concept Depending on Levels of Resilience and the Motivational Climate Directed towards Sport in Schoolchildren
Authors: Ramirez-Granizo Irwin Andrés , Sánchez-Zafra María , Zurita-Ortega Félix , Puertas-Molero Pilar , González-Valero Gabriel , Ubago-Jiménez Jose Luis
Published: January 2020

(1) Background: Motivation towards sports practice is fundamental at an early age, as this can favor the integral development of the student body. (2) Methods: The main objective of this study was to describe and analyze the relationships between the different dimensions of self-concept based on motivational climate, body mass index and resilience in a sample of 203 children from the third cycle of primary education, with an age between 11 and 13 years (M = 11.54). They completed the motivational climate questionnaires (PMCSQ-2), the self-concept questionnaire (AF-5) and the questionnaire that measures resilience levels (the Connor–Davidson Resilience Scale (CD-RISC)). (3) Results: The results showed that boys are more resilient than girls and, in turn, have a greater tendency to task climate compared to them. Regarding self-concept, males presented higher scores in the academic, social and physical dimensions. In the same line as resilience, the motivational climate in males is oriented to the ego climate and the feminine to the task climate. Negative correlations of physical self-concept were found with the ego and task climate. (4) Conclusions: The task climate was identified as a predictor of resilience levels.
Understanding the Factors Influencing Junior Doctors’ Career Decision-Making to Address Rural Workforce Issues: Testing a Conceptual Framework
Authors: Cuesta-Briand Beatriz , Coleman Mathew , Ledingham Rebekah , Moore Sarah , Wright Helen , Oldham David , Playford Denese
Published: January 2020

Medical graduates’ early career is known to be disorienting, and career decision-making is influenced by a complex set of factors. There is a strong association between rural background and rural undergraduate training and rural practice, and personal and family factors have been shown to influence workplace location, but the interaction between interest, training availability, and other work-relevant factors has not yet been fully explored. A qualitative study conducted by the Rural Clinical School of Western Australia (RCSWA) and WA Country Health Service (WACHS) explored factors influencing the decision to pursue rural work among junior doctors. Data collection and analysis was iterative. In total, 21 junior doctors were recruited to participate in semi-structured telephone interviews. Two main themes relating to the systems of influence on career decision-making emerged: (1) The importance of place and people, and (2) the broader context. We found that career decision-making among junior doctors is influenced by a complex web of factors operating at different levels. As Australia faces the challenge of developing a sustainable rural health workforce, developing innovative, flexible strategies that are responsive to the individual aspirations of its workforce whilst still meeting its healthcare service delivery needs will provide a way forward.
Preferences for Sweet and Fatty Taste in Children and Their Mothers in Association with Weight Status
Authors: Sobek Grzegorz , Łuszczki Edyta , Dąbrowski Mariusz , Dereń Katarzyna , Baran Joanna , Weres Aneta , Mazur Artur
Published: January 2020

Strong preferences for sweet and fat tastes (characters) are associated with the consumption of foods high in calories. The taste preferences, especially the sweet and fat tastes (characters), might be one of the factors predisposing children to become overweight and/or develop obesity. The aim of the study is to assess taste preferences in children and their mothers in association with their weight status. In the study, 150 children aged 8–15 were included; among them, 75 had overweight and/or obesity, and 150 mothers of whom 69 were overweight and/or obese. Body composition estimates were obtained using a bioelectrical impedance analysis-body height was measured using a stadiometerSeca 213. Sensory tests were carried out using apple juice of various sugar content and crackers of various fat content. Results show that children prefer a sweet taste more often than their mothers (50.0% vs. 35.3%, p = 0.009). In the group of children who preferred the high-sweet taste, there were twice as many obese children when compared to the group who preferred the low-sweet taste. Similar relationships applied to mothers. Preferences for fat taste (character) among mothers increased the risk of obesity among their children (39% vs. 20%; p = 0.039). Taste preferences, especially a sweet taste preference, seem to be one of the important factors determining overweight and obesity in children and adults. The fat taste(character) preferences in mothers correlate with the overweight and/or obesity of their children, while such preferences among children were not significantly different irrespective of body weight status.
How Does Walkability Change Behavior? A Comparison between Different Age Groups in the Netherlands
Authors: Liao Bojing , E. W. van den Berg Pauline , van Wesemael Pieter J. V. , A. Arentze Theo
Published: January 2020

Empirical research provides evidence that, in neighborhoods with higher walkability, individuals make more walking trips. However, it is not clear what the exact nature is of the relationships between neighborhood walkability and walking trips, since a higher walking frequency can be explained in different ways. This study examined whether the extra walking trips in better walkable neighborhoods are related primarily to trip generation, destination choice, or transport mode choice and whether this is the same for different age groups. A neighborhood fixed effects regression analysis was conducted in a first step to obtain a walkability measure for each neighborhood in the Netherlands including systematic as well as unobserved effects. Subsequently, the estimated fixed effects were used as walkability data for a path analysis based on a causal model to test the hypotheses stated. The results of the path analysis show direct relationships of neighborhood walkability with trip generation, destination choice, and transport mode choice, after controlling for the mutual relationships between the activity and trip variables. Comparing different age groups (i.e., children, adults, and elderly), the differences found mostly concerned the relationship between neighborhood walkability and trip generation. We concluded therefore that conditions for walkability are not the same for all age groups.
Metabolite Profiling Revealed That a Gardening Activity Program Improves Cognitive Ability Correlated with BDNF Levels and Serotonin Metabolism in the Elderly
Authors: Park Sin-Ae , Son Su Young , Lee A-Young , Park Hee-Geun , Lee Wang-Lok , Lee Choong Hwan
Published: January 2020

Metabolomics is useful for evaluating the fundamental mechanisms of improvements in the health functions of the elderly. Additionally, gardening intervention as a regular physical activity for the elderly maintained and improved physical, psychology, cognitive, and social health. This study was conducted to determine whether the cognitive ability of the elderly is affected by participating in a gardening activity program as a physical activity with a metabolomic potential biomarker. The gardening program was designed as a low to moderate intensity physical activity for the elderly. Serum metabolites resulting from gardening were subjected to metabolite profiling using gas chromatography time-of-flight mass spectrometry and ultra-high-performance liquid chromatography-linear trap quadruple-orbitrap-mass spectrometry followed by multivariate analyses. The partial least squares-discriminant analysis showed distinct clustering patterns among the control, non-gardening, and gardening groups. According to the pathway analysis, tryptophan metabolism including tryptophan, kynurenine, and serotonin showed significantly distinctive metabolites in the gardening group. Brain-derived neurotrophic factor levels (BDNF) in the gardening group were significantly increased after the gardening program. Correlation map analysis showed that the relative levels of tryptophan metabolites were positively correlated with BDNF. Our results show that tryptophan, kynurenine, and serotonin may be useful as metabolic biomarkers for improved cognitive ability by the gardening intervention.
A Comparison of Frequency- and Agreement-Based Response Formats in the Measurement of Burnout and Engagement
Authors: Tong Jiajin , Bickmeier Robert M. , Rogelberg Steven G.
Published: January 2020

The present research compares and contrasts frequency versus agreement response formats, two approaches to measuring job burnout and work engagement. Construct-based and measurement-based arguments for the superiority of the frequency response format in measuring burnout/engagement are provided, demonstrating that frequency-based measurements will explain relatively more variance in outcome variables. Fair comparison, time order counterbalance, and multiple measuring waves justify the comparison and reduce common method errors of self-report measures. Sample 1 (N = 242) was composed of employees from multiple organizations, while the participants in Sample 2 (N = 281) were employees from one company. Relative importance analysis showed that frequency outperforms the agreement response format in measuring burnout and engagement in both samples. These findings suggest that the frequency response format provides a more valuable method of detecting the dynamic nature of burnout/engagement, which offers methodological guidance for future research involving dynamic constructs. These findings can lead to improvements in the measurement of the dynamic experiences of burnout and engagement. This is one of the first studies to provide evidence whether the dynamic nature of the constructs would have any bearing on the response formats.
Assessing Emergency Shelter Demand Using POI Data and Evacuation Simulation
Authors: Chen Wei , Fang Yao , Zhai Qing , Wang Wei , Zhang Yijie
Published: January 2020

Mapping the fine-scale spatial distribution of emergency shelter demand is crucial for shelter planning during disasters. To provide shelter for people within a reasonable evacuation distance under day and night disaster scenarios, we formed an approach for examining the distribution of day and night shelter demand at the plot-scale using point of interest (POI) data, and then analyzed the supply and demand status of shelters after an evacuation simulation built in Python programming language. Taking the downtown areas of Guangzhou, China as a case study, the results show that significant differences exist in the size and spatial distribution of shelter demand in daytime and nighttime, and the total demand is 7.929 million people, which is far larger than the resident population. The average evacuation time of all 16,883 routes is 12.6 min, and after the evacuation, 558 of 888 shelters exceed their capacity to varying degrees, accounting for 62.84% of the total, indicating that the shelters cannot completely receive the potential evacuees. The method proposed in this paper provides a direct quantitative basis for the number and size of new shelter resources being planned during urban renewal activities, and form a reference for land reuse and disaster prevention space organization in future urban planning.
Optimization-Based Construction of Quadrilateral Table Cartograms
Authors: Inoue Ryo , Li Mao
Published: January 2020

A quadrilateral table cartogram is a rectangle-shaped figure that visualizes table-form data; quadrilateral cells in a table cartogram are transformed to express the magnitude of positive weights by their areas, while maintaining the adjacency of cells in the original table. However, the previous construction method is difficult to implement because it consists of multiple operations that do not have a unique solution and require complex settings to obtain the desired outputs. In this article, we propose a new construction for quadrilateral table cartograms by recasting the construction as an optimization problem. The proposed method is formulated as a simple minimization problem to achieve mathematical clarity. It can generate quadrilateral table cartograms with smaller deformation of rows and columns, thereby aiding readers to recognize the correspondence between table cartograms and original tables. In addition, we also propose a means of sorting rows and/or columns prior to the construction of table cartograms to reduce excess shape deformation. Applications of the proposed method confirm its capability to output table cartograms that clearly visualize the characteristics of datasets.
Crosstalk between NLRP12 and JNK during Hepatocellular Carcinoma
Authors: Khan Shahanshah , Zaki Hasan
Published: January 2020

Hepatocellular carcinoma (HCC), a leading cause of cancer-related death, is initiated and promoted by chronic inflammation. Inflammatory mediators are transcriptionally regulated by several inflammatory signaling pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). cJun N-terminal kinase (JNK), a member of the MAPK family, plays a central role in HCC pathogenesis. Pathogen-associated molecular patterns (PAMPs) activate JNK and other MAPK upon recognition by toll-like receptors (TLRs). Apart from TLRs, PAMPs are sensed by several other pattern recognition receptors, including cytosolic NOD-like receptors (NLRs). In a recent study, we demonstrated that the NLR member NLRP12 plays a critical role in suppressing HCC via negative regulation of the JNK pathway. This article briefly reviews the crosstalk between NLRP12 and JNK that occurs during HCC.
Finding the Keys to the CAR: Identifying Novel Target Antigens for T Cell Redirection Immunotherapies
Authors: Abbott Rebecca C. , Cross Ryan S. , Jenkins Misty R.
Published: January 2020

Oncology immunotherapy has been a significant advancement in cancer treatment and involves harnessing and redirecting a patient’s immune response towards their own tumour. Specific recognition and elimination of tumour cells was first proposed over a century ago with Paul Erlich’s ‘magic bullet’ theory of therapy. In the past decades, targeting cancer antigens by redirecting T cells with antibodies using either bispecific T cell engagers (BiTEs) or chimeric antigen receptor (CAR) T cell therapy has achieved impressive clinical responses. Despite recent successes in haematological cancers, linked to a high and uniformly expressed CD19 antigen, the efficacy of T cell therapies in solid cancers has been disappointing, in part due to antigen escape. Targeting heterogeneous solid tumours with T cell therapies will require the identification of novel tumour specific targets. These targets can be found among a range of cell-surface expressed antigens, including proteins, glycolipids or carbohydrates. In this review, we will introduce the current tumour target antigen classification, outline existing approaches to discover novel tumour target antigens and discuss considerations for future design of antibodies with a focus on their use in CAR T cells.
The Use of Nanomaterials in Tissue Engineering for Cartilage Regeneration; Current Approaches and Future Perspectives
Authors: Eftekhari Aziz , Maleki Dizaj Solmaz , Sharifi Simin , Salatin Sara , Rahbar Saadat Yalda , Zununi Vahed Sepideh , Samiei Mohammad , Ardalan Mohammadreza , Rameshrad Maryam , Ahmadian Elham , Cucchiarini Magali
Published: January 2020

The repair and regeneration of articular cartilage represent important challenges for orthopedic investigators and surgeons worldwide due to its avascular, aneural structure, cellular arrangement, and dense extracellular structure. Although abundant efforts have been paid to provide tissue-engineered grafts, the use of therapeutically cell-based options for repairing cartilage remains unsolved in the clinic. Merging a clinical perspective with recent progress in nanotechnology can be helpful for developing efficient cartilage replacements. Nanomaterials, < 100 nm structural elements, can control different properties of materials by collecting them at nanometric sizes. The integration of nanomaterials holds promise in developing scaffolds that better simulate the extracellular matrix (ECM) environment of cartilage to enhance the interaction of scaffold with the cells and improve the functionality of the engineered-tissue construct. This technology not only can be used for the healing of focal defects but can also be used for extensive osteoarthritic degenerative alterations in the joint. In this review paper, we will emphasize the recent investigations of articular cartilage repair/regeneration via biomaterials. Also, the application of novel technologies and materials is discussed.
Usefulness of the Inferior Articular Process’s Cross-Sectional Area as a Morphological Parameter for Predicting Central Lumbar Spinal Stenosis
Authors: Lee Sooho , Lim Taeha , Lim Young-Seob , Kim Young Uk
Published: January 2020

Hypertrophy of facet joints is associated with a high risk of central lumbar spinal stenosis (CLSS). However, no research has reported the effect of inferior articular process hypertrophy in CLSS. We hypothesize that the inferior articular process’s cross-sectional area (IAPCSA) is larger in patients with CLSS compared to those without CLSS. Data on IAPCSA were obtained from 116 patients with CLSS. A total of 102 control subjects underwent lumbar spine magnetic resonance imaging (LS-MRI) as part of a routine medical examination. Axial T1-weighted images were obtained from the two groups. Using an imaging analysis system, we investigated the cross-sectional area of the inferior articular process. The average IAPCSA was 70.97 ± 13.02 mm2 in control subjects and 88.77 ± 18.52 mm2 in patients with CLSS. CLSS subjects had significantly greater levels of IAPCSA (p < 0.001) than controls. A receiver operating characteristic (ROC) curve was plotted to determine the validity of IAPCSA as a predictor of CLSS. The most suitable cut-off point of IAPCSA for predicting CLSS was 75.88 mm2, with a sensitivity of 71.6%, a specificity of 68.6%, and an area under the curve (AUC) of 0.78 (95% CI: 0.72–0.84). Greater IAPCSA levels were associated with a higher incidence of CLSS. These results demonstrate that IAPCSA is a useful morphological predictor in the evaluation of CLSS.
Presbycusis: An Update on Cochlear Mechanisms and Therapies
Authors: Wang Jing , Puel Jean-Luc
Published: January 2020

Age-related hearing impairment (ARHI), also referred to as presbycusis, is the most common sensory impairment seen in the elderly. As our cochlea, the peripheral organ of hearing, ages, we tend to experience a decline in hearing and are at greater risk of cochlear sensory-neural cell degeneration and exacerbated age-related hearing impairments, e.g., gradual hearing loss, deterioration in speech comprehension (especially in noisy environments), difficulty in the localization sound sources, and ringing sensations in the ears. However, the aging process does not affect people uniformly; nor, in fact, does the aging process appear to be uniform even within an individual. Here, we outline recent research into chronological cochlear age in healthy people, and exacerbated hearing impairments during aging due to both extrinsic factors including noise and ototoxic medication, and intrinsic factors such as genetic predisposition, epigenetic factors, and aging. We review our current understanding of molecular pathways mediating ARHL and discuss recent discoveries in experimental hearing restoration and future prospects.
A Real-World Experience of Clinical, Biochemical and Genetic Assessment of Patients with Homozygous Familial Hypercholesterolemia
Authors: Di Taranto Maria Donata , Giacobbe Carola , Buonaiuto Alessio , Calcaterra Ilenia , Palma Daniela , Maione Giovanna , Iannuzzo Gabriella , Di Minno Matteo Nicola Dario , Rubba Paolo , Fortunato Giuliana
Published: January 2020

Homozygous familial hypercholesterolemia (HoFH), the severest form of familial hypercholesterolemia (FH), is characterized by very high LDL-cholesterol levels and a high frequency of coronary heart disease. The disease is caused by the presence of either a pathogenic variant at homozygous status or of two pathogenic variants at compound heterozygous status in the LDLR, APOB, PCSK9 genes. We retrospectively analyzed data of 23 HoFH patients (four children and 19 adults) identified during the genetic screening of 724 FH patients. Genetic screening was performed by sequencing FH causative genes and identifying large rearrangements of LDLR. Among the HoFH patients, four out of 23 (17.4%) were true homozygotes, whereas 19 out of 23 (82.6%) were compound heterozygotes for variants in the LDLR gene. Basal LDL-cholesterol was 12.9 ± 2.9 mmol/L. LDL-cholesterol levels decreased to 7.2 ± 1.8 mmol/L when treated with statin/ezetimibe and to 5.1 ± 3.1 mmol/L with anti-PCSK9 antibodies. Homozygous patients showed higher basal LDL-cholesterol and a poorer response to therapy compared with compound heterozygotes. Since 19 unrelated patients were identified in the Campania region (6,000,000 inhabitants) in southern Italy, the regional prevalence of HoFH was estimated to be at least 1:320,000. In conclusion, our results revealed a worse phenotype for homozygotes compared with compound heterozygotes, thereby highlighting the role of genetic screening in differentiating one genetic status from the other.
Targeting the Host for New Therapeutic Perspectives in Hepatitis D
Authors: Turon-Lagot Vincent , Saviano Antonio , Schuster Catherine , Baumert Thomas F. , Verrier Eloi R.
Published: January 2020

Hepatitis D virus (HDV) is a small satellite virus of hepatitis B virus (HBV) requiring HBV infection to complete its life cycle. It has been recently estimated that 13% of chronic HBV infected patients (60 million) are co-infected with HDV. Chronic hepatitis D is the most severe form of viral hepatitis with the highest risk to develop cirrhosis and liver cancer. Current treatment is based on pegylated-interferon-alpha which rarely controls HDV infection and is complicated by serious side effects. The development of novel antiviral strategies based on host targeting agents has shown promising results in phase I/II clinical trials. This review summarizes HDV molecular virology and physiopathology as well as new therapeutic approaches targeting HDV host factors.
Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update
Authors: Gellrich Frank , Schmitz Marc , Beissert Stefan , Meier Friedegund
Published: January 2020

Until recently, distant metastatic melanoma was considered refractory to systemic therapy. A better understanding of the interactions between tumors and the immune system and the mechanisms of regulation of T-cells led to the development of immune checkpoint inhibitors. This review summarizes the current novel data on the treatment of metastatic melanoma with anti-programmed cell death protein 1 (PD-1) antibodies and anti-PD-1-based combination regimens, including clinical trials presented at major conference meetings. Immune checkpoint inhibitors, in particular anti-PD-1 antibodies such as pembrolizumab and nivolumab and the combination of nivolumab with the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab can achieve long-term survival for patients with metastatic melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab were also approved for adjuvant treatment of patients with resected metastatic melanoma. Anti-PD-1 antibodies appear to be well tolerated, and toxicity is manageable. Nivolumab combined with ipilimumab achieves a 5 year survival rate of more than 50% but at a cost of high toxicity. Ongoing clinical trials investigate novel immunotherapy combinations and strategies (e.g., Talimogene laherparepvec (T-VEC), Bempegaldesleukin (BEMPEG), incorporation or sequencing of targeted therapy, incorporation or sequencing of radiotherapy), and focus on poor prognosis groups (e.g., high tumor burden/LDH levels, anti-PD-1 refractory melanoma, and brain metastases).
Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues
Authors: Portela Joana M. D. , Heckmann Laura , Wistuba Joachim , Sansone Andrea , van Pelt Ans M. M. , Kliesch Sabine , Schlatt Stefan , Neuhaus Nina
Published: January 2020

Cancer therapy and conditioning treatments of non-malignant diseases affect spermatogonial function and may lead to male infertility. Data on the molecular properties of spermatogonia and the influence of disease and/or treatment on spermatogonial subpopulations remain limited. Here, we assessed if the density and percentage of spermatogonial subpopulation changes during development (n = 13) and due to disease and/or treatment (n = 18) in tissues stored in fertility preservation programs, using markers for spermatogonia (MAGEA4), undifferentiated spermatogonia (UTF1), proliferation (PCNA), and global DNA methylation (5mC). Throughout normal prepubertal testicular development, only the density of 5mC-positive spermatogonia significantly increased with age. In comparison, patients affected by disease and/or treatment showed a reduced density of UTF1-, PCNA- and 5mC-positive spermatogonia, whereas the percentage of spermatogonial subpopulations remained unchanged. As an exception, sickle cell disease patients treated with hydroxyurea displayed a reduction in both density and percentage of 5mC- positive spermatogonia. Our results demonstrate that, in general, a reduction in spermatogonial density does not alter the percentages of undifferentiated and proliferating spermatogonia, nor the establishment of global methylation. However, in sickle cell disease patients’, establishment of spermatogonial DNA methylation is impaired, which may be of importance for the potential use of this tissues in fertility preservation programs.
Identification of Crack Length and Angle at the Center Weld Seam of Offshore Platforms Using a Neural Network Approach
Authors: Yang Qingxi , Li Gongbo , Mu Weilei , Liu Guijie , Sun Hailiang
Published: January 2020

The reconstruction algorithm for the probabilistic inspection of damage (RAPID) is aimed at localizing structural damage via the signal difference coefficient (SDC) between the signals of the present and reference conditions. However, tomography is only capable of presenting the approximate location and not the length and angle of defects. Therefore, a new quantitative evaluation method called the multiple back propagation neural network (Multi-BPNN) is proposed in this work. The Multi-BPNN employs SDC values as input variables and outputs the predicted length and angle, with each output node depending on an individual hidden layer. The cracks of different lengths and angles at the center weld seam of offshore platforms are simulated numerically. The SDC values of the simulations and experiments were normalized for each sample to eliminate external interference in the experiments. Then, the normalized simulation data were employed to train the proposed neural network. The results of the simulations and experimental verification indicated that the Multi-BPNN can effectively predict crack length and angle, and has better stability and generalization capacity than the multi-input to multi-output back propagation neural network.
A Cloud Based Disaster Management System
Authors: Cheikhrouhou Omar , Koubaa Anis , Zarrad Anis
Published: January 2020

The combination of wireless sensor networks (WSNs) and 3D virtual environments opens a new paradigm for their use in natural disaster management applications. It is important to have a realistic virtual environment based on datasets received from WSNs to prepare a backup rescue scenario with an acceptable response time. This paper describes a complete cloud-based system that collects data from wireless sensor nodes deployed in real environments and then builds a 3D environment in near real-time to reflect the incident detected by sensors (fire, gas leaking, etc.). The system’s purpose is to be used as a training environment for a rescue team to develop various rescue plans before they are applied in real emergency situations. The proposed cloud architecture combines 3D data streaming and sensor data collection to build an efficient network infrastructure that meets the strict network latency requirements for 3D mobile disaster applications. As compared to other existing systems, the proposed system is truly complete. First, it collects data from sensor nodes and then transfers it using an enhanced Routing Protocol for Low-Power and Lossy Networks (RLP). A 3D modular visualizer with a dynamic game engine was also developed in the cloud for near-real time 3D rendering. This is an advantage for highly-complex rendering algorithms and less powerful devices. An Extensible Markup Language (XML) atomic action concept was used to inject 3D scene modifications into the game engine without stopping or restarting the engine. Finally, a multi-objective multiple traveling salesman problem (AHP-MTSP) algorithm is proposed to generate an efficient rescue plan by assigning robots and multiple unmanned aerial vehicles to disaster target locations, while minimizing a set of predefined objectives that depend on the situation. The results demonstrate that immediate feedback obtained from the reconstructed 3D environment can help to investigate what–if scenarios, allowing for the preparation of effective rescue plans with an appropriate management effort.
Sustainable Land Management, Wildfire Risk and the Role of Grazing in Mediterranean Urban-Rural Interfaces: A Regional Approach from Greece
Authors: Colantoni Andrea , Egidi Gianluca , Quaranta Giovanni , D’Alessandro Roberto , Vinci Sabato , Turco Rosario , Salvati Luca
Published: January 2020

Mediterranean regions are likely to be the most vulnerable areas to wildfires in Europe. In this context, land-use change has promoted land abandonment and the consequent accumulation of biomass (fuel) in (progressively less managed) forests and (non-forest) natural land, causing higher fire density and severity, economic damage, and land degradation. The expansion of Wildland-Urban Interfaces (WUIs) further affects fire density by negatively impacting peri-urban farming and livestock density. Assuming the role of grazing in controlling fuel accumulation in forests and non-forest natural land as an indirect measure of wildfire containment around large Mediterranean cities, our work focuses on the role of nomadic livestock, i.e., sheep and goats—the most abundant and traditional farm species in the area. The present study (i) investigates the relationship between fire frequency/extent and livestock decline at the regional level in Greece, (ii) explores changes over time in regional wildfire regimes, comparing Attica, a particularly vulnerable peri-urban region which includes Athens (the Greek capital city), with the rest of the country, and (iii) quantifies trends over time in livestock characteristics (population structure and dynamics) over a sufficiently long time interval (1961–2017) at the same spatial scale, with the aim to document the progressive reduction of nomadic livestock in peri-urban districts. A comprehensive analysis of statistical data, corroborated with a literature review, outlined the relationship between livestock decline over time and changes in specific wildfire characteristics at the regional scale, evidencing peculiar environmental conditions in Attica. In this region, a rapid decline of nomadic livestock was observed compared to in the rest of Greece, leading to a higher wildfire risk. The results of this study suggest that nomadic livestock contributes to sustainable management of peri-urban land, stimulating grazing that may prevent fuel accumulation in fringe woodlands.
Turning Tissue Waste into High-Performance Microfiber Filters for Oily Wastewater Treatment
Authors: Wei Gaoliang , Dong Jun , Bai Jing , Zhao Yongsheng , Qin Chuanyu
Published: January 2020

Developing low-cost, durable, and high-performance materials for the separation of water/oil mixtures (free oil/water mixtures and emulsions) is critical to wastewater treatment and resource recovery. However, this currently remains a challenge. In this work, we report a biopolymer microfiber assembly, fabricated from the recovery of tissue waste, as a low-cost and high-performance filter for oily wastewater treatment. The microfiber filters demonstrate superhydrophilicity (water contact angle of 28.8°) and underwater superoleophobicity (oil contact angle of 154.2°), and thus can achieve separation efficiencies of >96% for both free oil/water mixtures and surfactant-stabilized emulsions even in highly acidic (pH 2.2)/alkaline (pH 11.8) conditions. Additionally, the prepared microfiber filters possess a much higher resistance to oil fouling than conventional membranes when filtering emulsions, which is because the large-sized 3D interconnected channels of the filters can delay the formation of a low-porosity oil gel layer on their surface. The filters are expected to practically apply for the oily wastewater treatment and reduce the amount of tissue waste entering the environment.
Characterization of PTFE Film on 316L Stainless Steel Deposited through Spin Coating and Its Anticorrosion Performance in Multi Acidic Mediums
Authors: Akram Waseem , Farhan Rafique Amer , Maqsood Nabeel , Khan Afzal , Badshah Saeed , Khan Rafi Ullah
Published: January 2020

Polytetrafluoroethylene (PTFE) was coated on 316L stainless steel (SS) substrate through a spin coating technique to enhance its corrosion resistance properties in hydrochloric acid (HCl) and nitric acid (HNO3) medium. Scanning electron microscopy (SEM) revealed the morphology of the coated and uncoated substrates and showed a uniform and crack-free PTFE coating on 316L SS substrate, while a damaged surface with thick corrosive layers was observed after the electrochemical test on the uncoated sample. However, an increased concentration of HCl and HNO3 slightly affected the surface morphology by covering the corrosive pits. An atomic force microscope (AFM) showed that the average surface roughness on 316L SS and PTFE coating was 26.3 nm and 24.1 nm, respectively. Energy dispersive X-ray spectroscopy (EDS) was used for the compositional analysis, which confirmed the presence of PTFE coating. The micro Vickers hardness test was used to estimate the hardness of 316L SS and PTFE-coated substrate, while the scratch test was used to study the adhesion properties of PTFE coating on 316L SS. The anticorrosion measurements of 316L SS and PTFE-coated substrates were made in various HCl and HNO3 solutions by using the electrochemical corrosion test. A comparison of the corrosion performance of PTFE-coated substrate with that of bare 316L SS substrate in HCl medium showed a protection efficiency (PE) of 96.7%, and in the case of HNO3 medium, the PE was 99.02%, by slightly shifting the corrosion potential of the coated sample towards the anodic direction.
Under-Drilling versus Hybrid Osseodensification Technique: Differences in Implant Primary Stability and Bone Density of the Implant Bed Walls
Authors: Delgado-Ruiz Rafael , Gold Joshua , Somohano Marquez Tanya , Romanos Georgios
Published: January 2020

The goal of this study was to evaluate the effects of two implant bed preparation techniques on the implant primary stability (IPS) and the bone density of the implant site. We completed 40 implant bed osteotomies in pig ribs using two techniques: osseodensification (OD) plus under-drilling (UD) with universal osseodensification drills (Test A), and under-drilling alone with drills of the same implant system (Test B). Implants with a 4.1 mm diameter and 10 mm length were inserted, and the IPS was evaluated with three methods: (insertion torque (IT), periotest (PTV), and resonance frequency analysis (RFA). The bone density was evaluated using micro-computed tomography. ANOVA and Tukey’s post-hoc test were used for comparison of the IPS values, and Kruskal–Wallis was used to evaluate the bone density. Statistical significance was set at p < 0.05. The tested B technique (UD) achieved a higher IPS compared to the Test A technique (OD + UD) for all the evaluation methods (p < 0.05). Bone density was higher at the apical and middle region in Test A compared to Test B and control sites (p < 0.05). We concluded that although the bone density increased with the hybrid OD technique with universal drills, implant beds prepared with UD using drills with geometry similar to that of the implant are more efficient at increasing IPS values.
Improving Initial Guess for the Iterative Solution of Linear Equation Systems in Incompressible Flow
Authors: Ye Shuai , Lin Yufei , Xu Liyang , Wu Jiaming
Published: January 2020

The pressure equation, generated while solving the incompressible Navier–Stokes equations with the segregated iterative algorithm such as PISO, produces a series of linear equation systems as the time step advances. In this paper, we target at accelerating the iterative solution of these linear systems by improving their initial guesses. We propose a weighted group extrapolation method to obtain a superior initial guess instead of a general one, the solution of the previous linear equation system. In this method, the previous solutions that are used to extrapolate the predicted solutions are carefully organized to address the oscillatory solution on each grid. The proposed method uses a weighted average of the predicted solutions as the new initial guess to avoid over extrapolating. Three numerical test results show that the proposed method can accelerate the iterative solution of most linear equation systems and reduce the simulation time up to 61.3%.