bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the Evaluation Index System of the Construction of Communities Suitable for Aging by the Fuzzy Delphi Method
Authors: Mei Wen-Bing , Hsu Che-Yu , Ou Sheng-Jung
Published: October 2020

In order to cope with the rapidly aging society and the Chinese traditional idea of old-age care, community home-based care has become a major mode of care for the aged in China, and the construction of communities suitable for the aged has also become the focus of the whole society. In order to build an objective and scientific evaluation index system of communities suitable for aging, the hierarchical structure and relative important values of the indicators for the assessment were obtained through data text rooted coding and the fuzzy Delphi expert questionnaire survey. The results prove that: the evaluation index system of communities suitable for aging consists of 4 criteria (i.e., humanistic care, public environment, health care, and economic security), 14 sub-criteria, and 48 evaluation indexes. The important values of the four criteria are “health care” (7.35), “public environment” (7.18), “humanistic care” (6.92), and “economic security” (6.87). This shows that with the aging of the elderly and the decline of physical function, health care is the most important material basis for community home care, and is also the core criterion for the construction of communities suitable for aging. Of the 48 important values of the evaluation indexes, “setting up an emergency assistance system” (7.89), “ensuring the accessibility of roads” (7.79), and “handling related affairs” (7.60) ranked the highest. This shows that the protection of the physical and mental health of the elderly and the rights and interests of the elderly are the core values of the construction of communities suitable for aging. This study believes that through constructing an evaluation index system of the communities suitable for aging, the past general constructions suitable for aging according to the standard can be further clarified through the scientific procedure of the ‘community suitable for aging construction evaluation method’, and be a reference for the academic and practical fields.
Secure Communication for Uplink Cellular Networks Assisted with Full-Duplex Device-to-Device User
Authors: Song Xin , Xia Lin , Xu Siyang , Wang Yue
Published: October 2020

In this paper, the secure communication based on the full-duplex (FD) device-to-device (D2D) in cellular networks is proposed. For the proposed scheme, the novel model is established, in which a D2D user is played as a relay operating in FD mode to assist in the secure transmission of uplink information. Considering that the D2D user as a relay is untrusted, D2D link rate maximization is formulated with the constraint of secrecy rate, which ensures the security of uplink cellular networks. To cope with the optimization problem, the optimal power allocation factors of the cellular user (CU) and the D2D user are jointly optimized. Firstly, by using the monotonicity of the objective function, the optimal solution of the power allocation factor at the D2D user can be obtained. Subsequently, the closed-form expression of the optimal power allocation factor at the CU is derived and verified that the solution is the global minimum point. Simulation results verify that the proposed scheme has better output performance than the conventional scheme.
An Analysis of the Mineral Composition of Pink Salt Available in Australia
Authors: Fayet-Moore Flavia , Wibisono Cinthya , Carr Prudence , Duve Emily , Petocz Peter , Lancaster Graham , McMillan Joanna , Marshall Skye , Blumfield Michelle
Published: October 2020

Little is known about the mineral composition of pink salt. The aim of this study was to evaluate for the first time the mineral composition of pink salt available for purchase in Australia and its implications for public health. Pink salt samples were purchased from retail outlets in two metropolitan Australian cities and one regional town. Color intensity, salt form, and country of origin were coded. A mass spectrometry scan in solids was used to determine the amount of 25 nutrients and non-nutritive minerals in pink salt (n = 31) and an iodized white table salt control (n = 1). A wide variation in the type and range of nutrients and non-nutritive minerals across pink salt samples were observed. One pink salt sample contained a level of lead (>2 mg/kg) that exceeded the national maximum contaminant level set by Food Standards Australia New Zealand. Pink salt in flake form, pink salt originating from the Himalayas, and darker colored pink salt were generally found to contain higher levels of minerals (p < 0.05). Despite pink salt containing nutrients, >30 g per day (approximately 6 teaspoons) would be required to make any meaningful contribution to nutrient intake, a level that would provide excessive sodium and potential harmful effects. The risk to public health from potentially harmful non-nutritive minerals should be addressed by Australian food regulations. Pink salt consumption should not exceed the nutrient reference values for Australia and New Zealand guidelines of <5 g of salt per day.
Non-Viable Lactobacillus johnsonii JNU3402 Protects against Diet-Induced Obesity
Authors: Yang Garam , Hong Eunjeong , Oh Sejong , Kim Eungseok
Published: October 2020

In this study, the role of non-viable Lactobacillus johnsonii JNU3402 (NV-LJ3402) in diet-induced obesity was investigated in mice fed a high-fat diet (HFD). To determine whether NV-LJ3402 exhibits a protective effect against diet-induced obesity, 7-week-old male C57BL/6J mice were fed a normal diet, an HFD, or an HFD with NV-LJ3402 for 14 weeks. NV-LJ3402 administration was associated with a significant reduction in body weight gain and in liver, epididymal, and inguinal white adipose tissue (WAT) and brown adipose tissue weight in HFD-fed mice. Concomitantly, NV-LJ3402 administration to HFD-fed mice also decreased the triglyceride levels in the plasma and metabolic tissues and slightly improved insulin resistance. Furthermore, NV-LJ3402 enhanced gene programming for energy dissipation in the WATs of HFD-fed mice as well as in 3T3-L1 adipocytes with increased peroxisome proliferator-activated receptor-γ (PPARγ) transcriptional activity, suggesting that the PPARγ pathway plays a key role in mediating the anti-obesity effect of NV-LJ3402 in HFD-fed mice. Furthermore, NV-LJ3402 administration in HFD-fed mice enhanced mitochondrial levels and function in WATs and also increased the body temperature upon cold exposure. Together, these results suggest that NV-LJ3402 could be safely used to develop dairy products that ameliorate diet-induced obesity and hyperlipidemia.
Age-Related Diseases and Driving Safety
Authors: Falkenstein Michael , Karthaus Melanie , Brüne-Cohrs Ute
Published: October 2020

Due to demographic changes, the number of older drivers is steadily increasing. Mobility is highly relevant for leading an independent life in the elderly. It largely depends on car driving, which is a complex task requiring a multitude of cognitive and motor skills vulnerable to age- related functional deterioration. The almost inevitable effects of senescence may be potentiated by age-related diseases, such as stroke or diabetes mellitus. Respective pharmacological treatment may cause side effects, additionally affecting driving safety. The present article reviews the impact of age-related diseases and drug treatment of these conditions on driving fitness in elderly drivers. In essence, we focus on diseases of the visual and auditory systems, diseases of the central nervous system (i.e., stroke, depression, dementia and mild cognitive disorder, and Parkinson’s disease), sleep disorders, as well as cardiovascular diseases, diabetes mellitus, musculoskeletal disorders, and frailty. We will outline the role of functional tests and the assessment of driving behavior (by a driving simulator or in real traffic), as well as the clinical interview including questions about frequency of (near) accidents, etc. in the evaluation of driving fitness of the elderly. We also address the impact of polypharmacy on driving fitness and end up with recommendations for physicians caring for older patients.
Optimization of Ecological Water Supplement Scheme for Improved Suitable Habitat Area for Rare Migratory Birds in Nature Reserves Using Interval-Parameter Fuzzy Two-Stage Stochastic Programming Model
Authors: Liao Xianrui , Meng Chong , Ren Zhixing , Zhao Wenjin
Published: October 2020

The optimization of ecological water supplement scheme in Momoge National Nature Reserve (MNNR), using an interval-parameter two-stage stochastic programming model (IPTSP), still experiences problems with fuzzy uncertainties and the wide scope of the obtained optimization schemes. These two limitations pose a high risk of system failure causing high decision risk for decision-makers and render it difficult to further undertake optimization schemes respectively. Therefore, an interval-parameter fuzzy two-stage stochastic programming (IPFTSP) model derived from an IPTSP model was constructed to address the random variable, the interval uncertainties and the fuzzy uncertainties in the water management system in the present study, to reduce decision risk and narrow down the scope of the optimization schemes. The constructed IPFTSP model was subsequently applied to the optimization of the ecological water supplement scheme of MNNR under different scenarios, to maximize the recovered habitat area and the carrying capacity for rare migratory water birds. As per the results of the IPFTSP model, the recovered habitat areas for rare migratory birds under low, medium and high flood flow scenarios were (14.06, 17.88) × 103, (14.92, 18.96) × 103 and (15.83, 19.43) × 103 ha, respectively, and the target value was (14.60, 18.47) × 103 ha with a fuzzy membership of (0.01, 0.83). Fuzzy membership reflects the possibility level that the model solutions satisfy the target value and the corresponding decision risk. We further observed that the habitat area recovered by the optimization schemes of the IPFTSP model was significantly increased compared to the recommended scheme, and the increases observed were (5.22%, 33.78%), (11.62%, 41.88%) and (18.44%, 45.39%). In addition, the interval widths of the recovered habitat areas in the IPFTSP model were reduced by 17.15%, 17.98% and 23.86%, in comparison to those from the IPTSP model. It was revealed that the IPFTSP model, besides generating the optimal decision schemes under different scenarios for decision-makers to select and providing decision space to adjust the decision schemes, also shortened the decision range, thereby reducing the decision risk and the difficulty of undertaking decision schemes. In addition, the fuzzy membership obtained from the IPFTSP model, reflecting the relationship among the possibility level, the target value, and the decision risk, assists the decision-makers in planning the ecological water supplement scheme with a preference for target value and decision risk.
Associations between High Serum Adipocyte Fatty Acid Binding Protein and First Hospitalization in Kidney Transplantation Patients: A 5-Year Follow-up Study
Authors: Lee Wei-Chen , Lee Ming-Che , Chen Ming-Chun , Hsu Bang-Gee
Published: October 2020

Adipocyte fatty acid binding protein (A-FABP) is predictive of type 2 diabetes mellitus incidences and metabolic syndrome and is independently associated with atherosclerosis. The present study aimed to assess the association between serum A-FABP levels and future first hospitalization events in kidney transplantation (KT). We enrolled 72 KT patients from January through April 2012 and followed up on these subjects until June 2017. The first hospitalization events incidence was the primary endpoint. Using a commercially available enzyme immunoassay, serum A-FABP levels were measured from the patient’s fasting blood samples. During a median 65-month follow-up, 49 first hospitalization events occurred. KT patients with first hospitalization events had greater incidences of hypertension, diabetes, and higher serum blood urea nitrogen, creatinine, triglyceride, and A-FABP levels than those without the events. Kaplan–Meier analysis showed that the cumulative incidence of first hospitalization events was greater in the high A-FABP group than in the low A-FABP group. Multivariate Cox analysis with significant variables showed that serum A-FABP (hazard ratio = 1.012; 95% confidence interval = 1.000–1.025; p = 0.044) was independently associated with first hospitalization events among KT patients. The results revealed that serum A-FABP is associated with first hospitalization events in KT patients. However, further prospective studies are needed to determine the mechanisms underlying this association.
Serum Calprotectin and Chemerin Concentrations as Markers of Low-Grade Inflammation in Prepubertal Children with Obesity
Authors: Rowicka Grażyna , Dyląg Hanna , Chełchowska Magdalena , Weker Halina , Ambroszkiewicz Jadwiga
Published: October 2020

In adults, obesity is associated with chronic low-grade inflammation, which may cause long-term adverse health consequences. We evaluated whether obesity in prepubertal children also generates this kind of inflammation and whether calprotectin and chemerin may be useful markers for early detection of such inflammation in this group of children. The study population included 83 children aged 2 to 10 years; 62 with obesity and without components of metabolic syndrome and 21 healthy controls with normal body weight. White blood cell (WBC) count, concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), calprotectin, and chemerin were determined in peripheral blood. Our study showed that in the group with obesity, serum concentrations of calprotectin and chemerin, as well as CRP were significantly higher as compared with the controls. We found a significant positive correlation between serum chemerin concentrations and BMI z-score (r = 0.33, p < 0.01) in children with obesity. Chemerin concentration was also positively correlated with CRP level (r = 0.36, p < 0.01) in the whole group of children. These findings suggest that obesity may generate chronic low-grade inflammation as early as in the prepubertal period which can be indicated by significantly higher serum concentrations of calprotectin and chemerin. Calprotectin and especially chemerin seem to be promising indicators of this type of inflammation in children with obesity, but the correlation between these markers requires further research.
A Multicenter, Prospective, Observational, Open-Label Study of the Safety and Comfort of Gensulin® Delivery Device Use in a Large Cohort of Adult and Elderly Patients with Type 2 Diabetes
Authors: Masierek Małgorzata , Nabrdalik Katarzyna , Kwiendacz Hanna , Sawczyn Tomasz , Gumprecht Janusz
Published: October 2020

Insulin treatment is necessary for many patients with type 2 diabetes, and its delivery must be safe and comfortable. This study evaluated patients’ safety and comfort when using a Gensulin® delivery device, GensuPen (Bioton), a reusable insulin pen device for injecting Gensulin® insulin among adult and elderly patients with type 2 diabetes. This was a 4-week multicenter, prospective, observational, open-label study in patients with diabetes mellitus type 2 who have recently started using a GensuPen. Overall, 10,309 patients (mean age: 63 ± 12.0 years; 47.9% female) were analyzed in this study. Of these, 2.5% had used an insulin delivery device before, and for 97.5%, GensuPen was the first delivery device they had used. Most (87.8%) of the patients rated the GensuPen as very good in setting the dose, 92.0% in confirmation of successful insulin administration, 80.9% in trigger location, and 75.0% in force needed for injection. The overall safety of the GensuPen use was high since severe hypoglycemia occurred only in 0.2% of the studied patients. There were 0.6% adverse events, none of which were serious. This real-life observation data shows that the GensuPen was well accepted and safe in this large patient population of adult and elderly patients with type 2 diabetes.
The Economic Burden of Cancers Attributable to Infection in the Republic of Korea: A Prevalence-Based Study
Authors: Nguyen Thi Xuan Trinh , Han Minji , Ki Moran , Kim Young Ae , Oh Jin-Kyoung
Published: October 2020

Infection is a major cause of cancers. We estimated the economic burden of cancers attributable to infection in 2014 in Korea, where cancer causing infection is prevalent, but the economic burden of it has never been examined. Cancer patients were defined as those having made medical claims as recorded by the National Health Insurance Service, which is a mandatory insurance for all citizen. We multiplied the costs by the population-attributable fraction for each type of cancer. The study included direct and indirect costs, where direct costs comprised direct medical and non-medical costs of inpatients and outpatients, while indirect costs were estimated by identifying future income loss due to premature death, productivity loss during hospitalization/outpatient visits, and job loss. In 2014, there were 100,054 infection-related cancer patients, accounting for 10.7% of all Korean cancer cases for that year. Direct costs of cancers associated with infection stood at nearly USD 676.9 million, while indirect costs were much higher at USD 2.57 billion. The average expenditure of a typical patient was USD 32,435. Economic burden of cancers attributable to infection is substantial in Korea, accounting for 0.23% of the national gross domestic product and 1.36% of national healthcare expenditure in 2014.
The Role of Sleep Quality, Trait Anxiety and Hypothalamic-Pituitary-Adrenal Axis Measures in Cognitive Abilities of Healthy Individuals
Authors: Labad Javier , Salvat-Pujol Neus , Armario Antonio , Cabezas Ángel , de Arriba-Arnau Aida , Nadal Roser , Martorell Lourdes , Urretavizcaya Mikel , Monreal José Antonio , Crespo José Manuel , Vilella Elisabet , Palao Diego José , Menchón José Manuel , Soria Virginia
Published: October 2020

Sleep plays a crucial role in cognitive processes. Sleep and wake memory consolidation seem to be regulated by glucocorticoids, pointing out the potential role of the hypothalamic-pituitary-adrenal (HPA) axis in the relationship between sleep quality and cognitive abilities. Trait anxiety is another factor that is likely to moderate the relationship between sleep and cognition, because poorer sleep quality and subtle HPA axis abnormalities have been reported in people with high trait anxiety. The current study aimed to explore whether HPA axis activity or trait anxiety moderate the relationship between sleep quality and cognitive abilities in healthy individuals. We studied 203 healthy individuals. We measured verbal and visual memory, working memory, processing speed, attention and executive function. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. Trait anxiety was assessed with the State-Trait Anxiety Inventory. HPA axis measures included the cortisol awakening response (CAR), diurnal cortisol slope and cortisol levels during the day. Multiple linear regression analyses explored the relationship between sleep quality and cognition and tested potential moderating effects by HPA axis measures and trait anxiety. Poor sleep quality was associated with poorer performance in memory, processing speed and executive function tasks. In people with poorer sleep quality, a blunted CAR was associated with poorer verbal and visual memory and executive functions, and higher cortisol levels during the day were associated with poorer processing speed. Trait anxiety was a moderator of visual memory and executive functioning. These results suggest that subtle abnormalities in the HPA axis and higher trait anxiety contribute to the relationship between lower sleep quality and poorer cognitive functioning in healthy individuals.
Assessment of the Range of Movement of the Lower Limb in Sport: Advantages of the ROM-SPORT I Battery
Authors: Cejudo Antonio , Sainz de Baranda Pilar , Ayala Francisco , De Ste Croix Mark , Santonja-Medina Fernando
Published: October 2020

Range of movement (ROM) assessment is an important strategy to increase physical-technical performance and minimize the risk of sports-related injuries. Currently, there is no consensus regarding which ROM assessment method is the most appropriate. The main objective of this study was to perform a systematic review of the test batteries available for the assessment of lower limb ROM; additionally, we compare the ROM-SPORT I battery with those previously reported in the literature. The systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The identification of publications was made by using the databases SciELO, Medline, Scopus, PubMed, and Web of Science. Based on the inclusion criteria, sixteen publications were selected and analyzed. The ROM-SPORT I battery is the most valid of the analyzed methods. This battery evaluates the ROM of eleven lower limb movements. The inclinometer with a telescopic arm and a box is a simpler, more comfortable, and faster procedure than others. The Lumbosant support and use of two examiners are essential to avoid compensatory movements to obtain reliable measurements during ROM assessment. The ROM-SPORT I is a field-based battery of tests that may be used by sports professionals, clinics, and researchers in applied settings to accurately assess and monitor lower extremity ROM.
Stigma, Health and Well-Being
Authors: Lin Chung-Ying , Tsang Hector W. H.
Published: October 2020

In order to understand the phenomenon of stigma in different populations (e.g., different ethnicities, different diseases, and different conditions), this Special Issue collects papers from around the world to illustrate the stigma phenomenon. After a rigorous process of peer review, a total of 24 papers were published and included in the Special Issue. These papers were contributed from different continents and countries, including the Americas (e.g., United States), Europe (e.g., Finland), and Asia (e.g., Saudi Arabia). Therefore, the diversity of ethnicity was ensured in the Special Issue. Moreover, these papers address different stigmatized populations/conditions (e.g., mental illness, obesity, public housing, homosexuality, and transgender). The most discussed populations were those with mental illness and those with obesity/overweight. However, additional evidence on the stigma topic is still needed. Specifically, future studies could consider the following directions to explore in depth the issues of stigma in different populations: (1) using longitudinal designs to understand the temporal or causal relationship between stigma and other related psychosocial factors; (2) designing treatment programs to fight stigma—this could be carried out in healthcare providers, healthcare trainees, the public, caregivers, and the stigmatized populations.
Work Schedule Irregularity and the Risk of Work-Related Injury among Korean Manual Workers
Authors: Lee Won-Tae , Lim Sung-Shil , Kim Jihyun , Yun Sehyun , Yoon Jin-Ha , Won Jong-Uk
Published: October 2020

Work schedules comprise various variables and generate health and safety outcomes, including work-related injury, which causes socioeconomic problems, such as productivity loss and damage to worker health. We investigated the association between work schedule irregularity and the incidence of work-related injury among South Korean manual workers using data from the 5th Korean Working Conditions Survey. In total, 18,330 manual workers were included. A multivariate logistic regression analysis was performed to understand the association between work schedule and work-related injury and the influence of sufficient safety information and work schedule on work-related injury. We calculated the influence of an irregular work schedule on occupational injury after controlling for personal and work environment-related factors. The adjusted odds ratio (OR) for work-related injury was 1.66 (95% confidence interval (CI) 1.32–2.09) for an irregular work schedule. The interaction had an additive effect when the work schedule was irregular, even when sufficient safety information was provided. Manual workers had a higher incidence of injury (2.1%). Even in adjusted analyses, work schedule irregularity conferred greater risks of work injury, particularly when not working the same number of days weekly (OR 1.52, 95% CI 1.21–1.90). Policymakers and health professionals need to consider the impact of work schedule irregularity on worker safety and health.
Multiple-Purpose Connectivity Map Analysis Reveals the Benefits of Esculetin to Hyperuricemia and Renal Fibrosis
Authors: Wang Yiming , Kong Weikaixin , Wang Liang , Zhang Tianyu , Huang Boyue , Meng Jia , Yang Baoxue , Xie Zhengwei , Zhou Hong
Published: October 2020

Hyperuricemia (HUA) is a risk factor for chronic kidney disease (CKD). Serum uric acid (SUA) levels in CKD stage 3–4 patients closely correlate with hyperuricemic nephropathy (HN) morbidity. New uric acid (UA)-lowering strategies are required to prevent CKD. The multiple-purpose connectivity map (CMAP) was used to discover potential molecules against HUA and renal fibrosis. We used HUA and unilateral ureteral occlusion (UUO) model mice to verify renoprotective effects of molecules and explore related mechanisms. In vitro experiments were performed in HepG2 and NRK-52E cells induced by UA. Esculetin was the top scoring compound and lowered serum uric acid (SUA) levels with dual functions on UA excretion. Esculetin exerted these effects by inhibiting expression and activity of xanthine oxidase (XO) in liver, and modulating UA transporters in kidney. The mechanism by which esculetin suppressed XO was related to inhibiting the nuclear translocation of hexokinase 2 (HK2). Esculetin was anti-fibrotic in HUA and UUO mice through inhibiting TGF-β1-activated profibrotic signals. The renoprotection effects of esculetin in HUA mice were associated with lower SUA, alleviation of oxidative stress, and inhibition of fibrosis. Esculetin is a candidate urate-lowering drug with renoprotective activity and the ability to inhibit XO, promote excretion of UA, protect oxidative stress injury, and reduce renal fibrosis.
Three-Dimensional Structures of Carbohydrates and Where to Find Them
Authors: Scherbinina Sofya I. , Toukach Philip V.
Published: October 2020

Analysis and systematization of accumulated data on carbohydrate structural diversity is a subject of great interest for structural glycobiology. Despite being a challenging task, development of computational methods for efficient treatment and management of spatial (3D) structural features of carbohydrates breaks new ground in modern glycoscience. This review is dedicated to approaches of chemo- and glyco-informatics towards 3D structural data generation, deposition and processing in regard to carbohydrates and their derivatives. Databases, molecular modeling and experimental data validation services, and structure visualization facilities developed for last five years are reviewed.
Impact of Mitophagy and Mitochondrial Unfolded Protein Response as New Adaptive Mechanisms Underlying Old Pathologies: Sarcopenia and Non-Alcoholic Fatty Liver Disease
Authors: Urbina-Varela Rodrigo , Castillo Nataly , Videla Luis A. , del Campo Andrea
Published: October 2020

Mitochondria are the first-line defense of the cell in the presence of stressing processes that can induce mitochondrial dysfunction. Under these conditions, the activation of two axes is accomplished, namely, (i) the mitochondrial unfolded protein response (UPRmt) to promote cell recovery and survival of the mitochondrial network; (ii) the mitophagy process to eliminate altered or dysfunctional mitochondria. For these purposes, the former response induces the expression of chaperones, proteases, antioxidant components and protein import and assembly factors, whereas the latter is signaled through the activation of the PINK1/Parkin and BNIP3/NIX pathways. These adaptive mechanisms may be compromised during aging, leading to the development of several pathologies including sarcopenia, defined as the loss of skeletal muscle mass and performance; and non-alcoholic fatty liver disease (NAFLD). These age-associated diseases are characterized by the progressive loss of organ function due to the accumulation of reactive oxygen species (ROS)-induced damage to biomolecules, since the ability to counteract the continuous and large generation of ROS becomes increasingly inefficient with aging, resulting in mitochondrial dysfunction as a central pathogenic mechanism. Nevertheless, the role of the integrated stress response (ISR) involving UPRmt and mitophagy in the development and progression of these illnesses is still a matter of debate, considering that some studies indicate that the prolonged exposure to low levels of stress may trigger these mechanisms to maintain mitohormesis, whereas others sustain that chronic activation of them could lead to cell death. In this review, we discuss the available research that contributes to unveil the role of the mitochondrial UPR in the development of sarcopenia, in an attempt to describe changes prior to the manifestation of severe symptoms; and in NAFLD, in order to prevent or reverse fat accumulation and its progression by means of suitable protocols to be addressed in future studies.
Nonsequential Splicing Events Alter Antisense-Mediated Exon Skipping Outcome in COL7A1
Authors: Ham Kristin A. , Aung-Htut May Thandar , Fletcher Sue , Wilton Steve D.
Published: October 2020

The COL7A1 gene encodes homotrimer fibrils essential for anchoring dermal and epidermal layers, and pathogenic mutations in COL7A1 can cause recessive or dominant dystrophic epidermolysis bullosa. As a monogenic disease gene, COL7A1 constitutes a potential target for antisense oligomer-mediated exon skipping, a therapy applicable to a growing number of other genetic disorders. However, certain characteristics of COL7A1: many exons, low average intron size, and repetitive and guanine-cytosine rich coding sequence, present challenges to the design of specific and effective antisense oligomers. While targeting COL7A1 exons 10 and 73 for excision from the mature mRNA, we discovered that antisense oligomers comprised of 2′-O-methyl modified bases on a phosphorothioate backbone and phosphorodiamidate morpholino oligomers produced similar, but distinctive, splicing patterns including excision of adjacent nontargeted exons and/or retention of nearby introns in some transcripts. We found that the nonsequential splicing of certain introns may alter pre-mRNA processing during antisense oligomer-mediated exon skipping and, therefore, additional studies are required to determine if the order of intron removal influences multiexon skipping and/or intron retention in processing of the COL7A1 pre-mRNA.
Setup and Validation of a Reliable Docking Protocol for the Development of Neuroprotective Agents by Targeting the Sigma-1 Receptor (S1R)
Authors: Rossino Giacomo , Rui Marta , Pozzetti Luca , Schepmann Dirk , Wünsch Bernhard , Zampieri Daniele , Pellavio Giorgia , Laforenza Umberto , Rinaldi Silvia , Colombo Giorgio , Morelli Laura , Linciano Pasquale , Rossi Daniela , Collina Simona
Published: October 2020

Sigma-1 receptor (S1R) is a promising molecular target for the development of novel effective therapies against neurodegenerative diseases. To speed up the discovery of new S1R modulators, herein we report the development of a reliable in silico protocol suitable to predict the affinity of small molecules against S1R. The docking method was validated by comparing the computational calculated Ki values of a test set of new aryl-aminoalkyl-ketone with experimental determined binding affinity. The druggability profile of the new compounds, with particular reference to the ability to cross the blood–brain barrier (BBB) was further predicted in silico. Moreover, the selectivity over Sigma-2 receptor (S2R) and N-methyl-d-aspartate (NMDA) receptor, another protein involved in neurodegeneration, was evaluated. 1-([1,1’-biphenyl]-4-yl)-4-(piperidin-1-yl)butan-1-one (12) performed as the best compound and was further investigated for acetylcholinesterase (AchE) inhibitor activity and determination of antioxidant activity mediated by aquaporins (AQPs). With a good affinity against both S1R and NMDA receptor, good selectivity over S2R and favorable BBB penetration potential together with its AChE inhibitory activity and its ability to exert antioxidant effects through modulation of AQPs, 12 represents a viable candidate for further development as a neuroprotective agent.
Adipokines and Inflammation: Focus on Cardiovascular Diseases
Authors: Feijóo-Bandín Sandra , Aragón-Herrera Alana , Moraña-Fernández Sandra , Anido-Varela Laura , Tarazón Estefanía , Roselló-Lletí Esther , Portolés Manuel , Moscoso Isabel , Gualillo Oreste , González-Juanatey José Ramón , Lago Francisca
Published: October 2020

It is well established that adipose tissue, apart from its energy storage function, acts as an endocrine organ that produces and secretes a number of bioactive substances, including hormones commonly known as adipokines. Obesity is a major risk factor for the development of cardiovascular diseases, mainly due to a low grade of inflammation and the excessive fat accumulation produced in this state. The adipose tissue dysfunction in obesity leads to an aberrant release of adipokines, some of them with direct cardiovascular and inflammatory regulatory functions. Inflammation is a common link between obesity and cardiovascular diseases, so this review will summarise the role of the main adipokines implicated in the regulation of the inflammatory processes occurring under the scenario of cardiovascular diseases.
Genome-Wide Identification of the Gossypium hirsutum NHX Genes Reveals That the Endosomal-Type GhNHX4A Is Critical for the Salt Tolerance of Cotton
Authors: Ma Wenyu , Ren Zhongying , Zhou Yang , Zhao Junjie , Zhang Fei , Feng Junping , Liu Wei , Ma Xiongfeng
Published: October 2020

Soil salinization, which is primarily due to excessive Na+ levels, is a major abiotic stress adversely affecting plant growth and development. The Na+/H+ antiporter (NHX) is a transmembrane protein mediating the transport of Na+ or K+ and H+ across the membrane to modulate the ionic balance of plants in response to salt stress. Research regarding NHXs has mainly focused on the vacuolar-type NHX family members. However, the biological functions of the endosomal-type NHXs remain relatively uncharacterized. In this study, 22 NHX family members were identified in Gossypium hirsutum. A phylogenetic analysis divided the GhNHX genes into two categories, with 18 and 4 in the vacuolar and endosomal groups, respectively. The chromosomal distribution of the NHX genes revealed the significant impact of genome-wide duplication during the polyploidization process on the number of GhNHX genes. Analyses of gene structures and conserved motifs indicated that GhNHX genes in the same phylogenetic cluster are conserved. Additionally, the salt-induced expression patterns confirmed that the expression levels of most of the GhNHX genes are affected by salinity. Specifically, in the endosomal group, GhNHX4A expression was substantially up-regulated by salt stress. A yeast functional complementation test proved that GhNHX4A can partially restore the salt tolerance of the salt-sensitive yeast mutant AXT3. Silencing GhNHX4A expression decreased the resistance of cotton to salt stress because of an increase in the accumulation of Na+ in stems and a decrease in the accumulation of K+ in roots. The results of this study may provide the basis for an in-depth characterization of the regulatory functions of NHX genes related to cotton salt tolerance, especially the endosomal-type GhNHX4A. Furthermore, the presented data may be useful for selecting appropriate candidate genes for the breeding of new salt-tolerant cotton varieties.
Endoglin Promotes Myofibroblast Differentiation and Extracellular Matrix Production in Diabetic Nephropathy
Authors: Gerrits Tessa , Zandbergen Malu , Wolterbeek Ron , Bruijn Jan A. , Baelde Hans J. , Scharpfenecker Marion
Published: October 2020

Diabetic nephropathy (DN) is a complication of diabetes mellitus that can lead to proteinuria and a progressive decline in renal function. Endoglin, a co-receptor of TGF-β, is known primarily for regulating endothelial cell function; however, endoglin is also associated with hepatic, cardiac, and intestinal fibrosis. This study investigates whether endoglin contributes to the development of interstitial fibrosis in DN. Kidney autopsy material from 80 diabetic patients was stained for endoglin and Sirius Red and scored semi-quantitatively. Interstitial endoglin expression was increased in samples with DN and was correlated with Sirius Red staining (p < 0.001). Endoglin expression was also correlated with reduced eGFR (p = 0.001), increased creatinine (p < 0.01), increased systolic blood pressure (p < 0.05), hypertension (p < 0.05), and higher IFTA scores (p < 0.001). Biopsy samples from DN patients were also co-immunostained for endoglin together with CD31, CD68, vimentin, or α-SMA Endoglin co-localized with both the endothelial marker CD31 and the myofibroblast marker α-SMA. Finally, we used shRNA to knockdown endoglin expression in a human kidney fibroblast cell line. We found that TGF-β1 stimulation upregulated SERPINE1, CTGF, and ACTA2 mRNA and α-SMA protein, and that these effects were significantly reduced in fibroblasts after endoglin knockdown. Taken together, these data suggest that endoglin plays a role in the pathogenesis of interstitial fibrosis in DN.
Rapid Expansion of Virus-Specific CD4+ T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus
Authors: Kang Hyun Seok , Hou Wanqiu , Kim Byung S.
Published: October 2020

The infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) induces a T cell-mediated demyelinating disease. This system has been studied as a relevant infection model for multiple sclerosis (MS). Therefore, defining the type of T cell responses and their functions is critically important for understanding the relevant pathogenic mechanisms. In this study, we adoptively transferred naive VP2-specific TCR-Tg CD4+ T cells into syngeneic susceptible SJL mice and monitored the development of the disease and the activation and proliferation of CD4+ T cells during the early stages of viral infection. The preexisting VP2-specific naive CD4+ T cells promoted the pathogenesis of the disease in a dose-dependent manner. The transferred VP2-specific CD4+ T cells proliferated rapidly in the CNS starting at 2–3 dpi. High levels of FoxP3+CD4+ T cells were found in the CNS early in viral infection (3 dpi) and persisted throughout the infection. Activated VP2-specific FoxP3+CD4+ T cells inhibited the production of IFN-γ, but not IL-17, via the same VP2-specific CD4+ T cells without interfering in proliferation. Thus, the early presence of regulatory T cells in the CNS with viral infection may favor the induction of pathogenic Th17 cells over protective Th1 cells in susceptible mice, thereby establishing the pathogenesis of virus-induced demyelinating disease.
Single-Dose Cisplatin Pre-Treatment Enhances Efficacy of ROBO1-Targeted Radioimmunotherapy
Authors: Fujiwara Kentaro , Koyama Keitaro , Tsuji Atsushi B. , Iwanari Hiroko , Kusano-Arai Osamu , Higashi Tatsuya , Momose Toshimitsu , Hamakubo Takao
Published: October 2020

We previously reported that radioimmunotherapy (RIT) using 90Y-labeled anti-ROBO1 IgG (90Y-B5209B) achieved significant anti-tumor effects against small-cell lung cancer (SCLC) xenografts. However, subsequent tumor regrowth suggested the necessity for more effective therapy. Here, we evaluated the efficacy of combination 90Y-B5209B and cisplatin therapy in NCI-H69 SCLC xenograft mice. Mice were divided into four therapeutic groups: saline, cisplatin only, RIT only, or combination therapy. Either saline or cisplatin was administered by injection one day prior to the administration of either saline or 90Y-B5209B. Tumor volume, body weight, and blood cell counts were monitored. The pathological analysis was performed on day seven post injection of 90Y-B5209B. The survival duration of the combination therapy group was significantly longer than that of the group treated with RIT alone. No significant survival benefit was observed following the isolated administration of cisplatin (relative to saline). Pathological changes following combination therapy were more significant than those following the isolated administration of RIT. Although combination therapy was associated with an increase of several adverse effects such as weight loss and pancytopenia, these were transient. Thus, cisplatin pre-treatment can potentially enhance the efficacy of 90Y-B5209B, making it a promising therapeutic strategy for SCLC.
Insights into the Function and Evolution of Taste 1 Receptor Gene Family in the Carnivore Fish Gilthead Seabream (Sparus aurata)
Authors: Angotzi Anna Rita , Puchol Sara , Cerdá-Reverter Jose M. , Morais Sofia
Published: October 2020

A plethora of molecular and functional studies in tetrapods has led to the discovery of multiple taste 1 receptor (T1R) genes encoding G-protein coupled receptors (GPCRs) responsible for sweet (T1R2 + T1R3) and umami (T1R1 + T1R3) taste. In fish, the T1R gene family repertoires greatly expanded because of several T1R2 gene duplications, and recent studies have shown T1R2 functional divergence from canonical mammalian sweet taste perceptions, putatively as an adaptive mechanism to develop distinct feeding strategies in highly diverse aquatic habitats. We addressed this question in the carnivore fish gilthead seabream (Sparus aurata), a model species of aquaculture interest, and found that the saT1R gene repertoire consists of eight members including saT1R1, saT1R3 and six saT1R2a-f gene duplicates, adding further evidence to the evolutionary complexity of fishT1Rs families. To analyze saT1R taste functions, we first developed a stable gene reporter system based on Ca2+-dependent calcineurin/NFAT signaling to examine specifically in vitro the responses of a subset of saT1R heterodimers to L-amino acids (L-AAs) and sweet ligands. We show that although differentially tuned in sensitivity and magnitude of responses, saT1R1/R3, saT1R2a/R3 and saT1R2b/R3 may equally serve to transduce amino acid taste sensations. Furthermore, we present preliminary information on the potential involvement of the Gi protein alpha subunits saGαi1 and saGαi2 in taste signal transduction.
Toward Evaluation of the Subjective Experience of a General Class of User-Controlled, Robot-Mediated Rehabilitation Technologies for Children with Neuromotor Disability
Authors: Schladen Manon Maitland , Cleary Kevin , Koumpouros Yiannis , Monfaredi Reza , Salvador Tyler , Talari Hadi Fooladi , Slagle Jacob , Coley Catherine , Kovelman Staci , Belschner Justine , Evans Sarah Helen
Published: October 2020

Technological advances in game-mediated robotics provide an opportunity to engage children with cerebral palsy (CP) and other neuromotor disabilities in more frequent and intensive therapy by making personalized, programmed interventions available 24/7 in children’s homes. Though shown to be clinically effective and feasible to produce, little is known of the subjective factors impacting acceptance of what we term assistive/rehabilitative (A/R) gamebots by their target populations. This research describes the conceptualization phase of an effort to develop a valid and reliable instrument to guide the design of A/R gamebots. We conducted in-depth interviews with 8 children with CP and their families who had trialed an exemplar A/R gamebot, PedBotHome, for 28 days in their homes. The goal was to understand how existing theories and instruments were either appropriate or inappropriate for measuring the subjective experience of A/R gamebots. Key findings were the importance of differentiating the use case of therapy from that of assistance in rehabilitative technology assessment, the need to incorporate the differing perspectives of children with CP and those of their parents into A/R gamebot evaluation, and the potential conflict between the goals of preserving the quality of the experience of game play for the child while also optimizing the intensity and duration of therapy provided during play.
Changes in the Honeybee Antioxidant System after 12 h of Exposure to Electromagnetic Field Frequency of 50 Hz and Variable Intensity
Authors: Migdał Paweł , Murawska Agnieszka , Strachecka Aneta , Bieńkowski Paweł , Roman Adam
Published: October 2020

In recent years, on a global scale, more and more reports of a phenomenon called CCD (Colony Collapse Disorder) have been reported. In addition to pesticides, diseases, and other environmental stressors, electromagnetic fields are also mentioned as one of the possible causes of CCD. One of the body’s first lines of defense against harmful factors is the antioxidant system. We hypothesized that electromagnetic field upregulate the activity of SOD (superoxide dismutase), CAT (catalases), and changed FRAP (total antioxidant potential) in honeybee hemolymph. In our research, 12 h bee’s exposure to E-field was analyzed to determine changes in the antioxidant system. The frequency of 50 Hz and various intensities were used: 5.0 kV/m, 11.5 kV/m, 23.0 kV/m, and 34.5 kV/m. Superoxide dismutase was characterized by four times higher activity in the study groups as compared to the control group. Catalase activity in all groups was characterized by statistically significantly different activity between the groups. The highest activity was recorded in the 34.5 kV/m group. The lowest activity was recorded in the 11.5 kV/m group. A relationship was found between different E-field intensities and changes in the antioxidant system.
Can Additional Patient Information Improve the Diagnostic Performance of Deep Learning for the Interpretation of Knee Osteoarthritis Severity
Authors: Kim Dong Hyun , Lee Kyong Joon , Choi Dongjun , Lee Jae Ik , Choi Han Gyeol , Lee Yong Seuk
Published: October 2020

The study compares the diagnostic performance of deep learning (DL) with that of the former radiologist reading of the Kellgren–Lawrence (KL) grade and evaluates whether additional patient data can improve the diagnostic performance of DL. From March 2003 to February 2017, 3000 patients with 4366 knee AP radiographs were randomly selected. DL was trained using knee images and clinical information in two stages. In the first stage, DL was trained only with images and then in the second stage, it was trained with image data and clinical information. In the test set of image data, the areas under the receiver operating characteristic curve (AUC)s of the DL algorithm in diagnosing KL 0 to KL 4 were 0.91 (95% confidence interval (CI), 0.88–0.95), 0.80 (95% CI, 0.76–0.84), 0.69 (95% CI, 0.64–0.73), 0.86 (95% CI, 0.83–0.89), and 0.96 (95% CI, 0.94–0.98), respectively. In the test set with image data and additional patient information, the AUCs of the DL algorithm in diagnosing KL 0 to KL 4 were 0.97 (95% confidence interval (CI), 0.71–0.74), 0.85 (95% CI, 0.80–0.86), 0.75 (95% CI, 0.66–0.73), 0.86 (95% CI, 0.79–0.85), and 0.95 (95% CI, 0.91–0.97), respectively. The diagnostic performance of image data with additional patient information showed a statistically significantly higher AUC than image data alone in diagnosing KL 0, 1, and 2 (p-values were 0.008, 0.020, and 0.027, respectively).The diagnostic performance of DL was comparable to that of the former radiologist reading of the knee osteoarthritis KL grade. Additional patient information improved DL diagnosis in interpreting early knee osteoarthritis.