bluuebunny/crossref_metadata_2025 huggingface dataset:
Alleviating insomnia should decrease the risk of irritable bowel syndrome: Evidence from Mendelian randomization
Authors: Bao Wenzhao , Qi Li , Bao Yin , Wang Sai , Li Wei
Published: August 2022

Background: Associations have been reported between sleep and irritable bowel syndrome (IBS). However, whether there exists a causation between them is still unknown.

Methods: We employed the Mendelian randomization (MR) design to explore the causal relationship between sleep and IBS. All genetic associations with sleep-related traits reached genome-wide significance (p-value < 5 × 10-8). The genetic associations with IBS were obtained from two independent large genome-wide association studies (GWAS), where non-FinnGen GWAS was in the discovery stage and FinnGen GWAS was in the validation stage. Primarily, the inverse-variance weighted method was employed to estimate the causal effects, and a meta-analysis was performed to combine the MR estimates.

Results: In the discovery, we observed that genetic liability to the “morning” chronotype could lower the risk of IBS [OR = 0.81 (0.76, 0.86)]. Also, the genetic liability to insomnia can increase the risk of IBS [OR = 2.86 (1.94, 4.23)] and such causation was supported by short sleep duration. In the validation stage, only insomnia displayed statistical significance [OR = 2.22 (1.09, 4.51)]. The meta-analysis suggested two genetically-determined sleep exposures can increase the risk of IBS, including insomnia [OR = 2.70 (1.92, 3.80)] and short sleep duration [OR = 2.46 (1.25, 4.86)]. Furthermore, the multivariable MR analysis suggested insomnia is an independent risk factor for IBS after adjusting for chronotype [OR = 2.32 (1.57, 3.43)] and short sleep duration [OR = 1.45 (1.13, 1.85)]. IBS cannot increase the risk of insomnia in the reverse MR analysis.

Conclusion: Genetic susceptibility to insomnia can increase the risk of IBS, and improving sleep quality, especially targeting insomnia, can help to prevent IBS.
Modulation of Leukocyte Subsets Mobilization in Response to Exercise by Water Immersion Recovery
Authors: Ottone Vinícius de Oliveira , De Paula Fabrício , Brozinga Paula Fernandes Aguiar , Matos Mariana Aguiar de , Duarte Tamiris Campos , Costa Karine Beatriz , Garcia Bruna Caroline Chaves , Silva Thyago José , Magalhães Flavio De Castro , Coimbra Cândido Celso , Esteves Elizabethe Adriana , Pinto Kelerson Mauro de Castro , Amorim Fabiano Trigueiro , Rocha-Vieira Etel
Published: August 2022

Purpose:To investigate the effect of different water immersion temperatures on the kinetics of blood markers of skeletal muscle damage and the main leukocyte subpopulations.

Methods:Eleven recreationally trained young men participated in four experimental sessions consisting of unilateral eccentric knee flexion and 90 min of treadmill running at 70% of peak oxygen uptake, followed by 15 min of water immersion recovery at 15, 28 or 38°C. In the control condition participants remained seated at room temperature. Four hours after exercise recovery, participants completed a performance test. Blood samples were obtained before and immediately after exercise, after immersion, immediately before and after the performance test and 24 h after exercise. The number of leukocyte populations and the percentage of lymphocyte and monocytes subsets, as well as the serum activity of creatine kinase and aspartate aminotransferase were determined.

Results:Leukocytosis and increase in blood markers of skeletal muscle damage were observed after the exercise. Magnitude effect analysis indicated that post-exercise hot-water immersion likely reduced the exercise-induced lymphocytosis and monocytosis. Despite reduced monocyte count, recovery by 38°C immersion, as well as 28°C, likely increased the percentage of non-classical monocytes in the blood. The percentage of CD25+cells in the CD4 T cell subpopulation was possibly lower after immersion in water at 28 and 15°C. No effect of recovery by water immersion was observed for serum levels of creatine kinase and aspartate aminotransferase.

Conclusions:Recovery by hot-water immersion likely attenuated the leukocytosis and increased the mobilization of non-classical monocytes induced by a single session of exercise combining resistance and endurance exercises, despite no effect of water immersion on markers of skeletal muscle damage. The monocyte response mediated by hot water immersion may lead to the improvement of the inflammatory response evoked by exercise in the skeletal muscle.
Thinking on your feet: Beauty and auto small businesses maneuver the risks of the COVID-19 pandemic
Authors: Moreno Ramírez Denise , Gutenkunst Shannon , Honan Jenna , Ingram Maia , Quijada Carolina , Chaires Marvin , Sneed Sam J. , Sandoval Flor , Spitz Rachel , Carvajal Scott , Billheimer Dean , Wolf Ann Marie , Beamer Paloma I.
Published: August 2022

On March 11, 2020, the World Health Organization officially declared SARS-CoV-2 a pandemic, and governments and health institutions enacted various public health measures to decrease its transmission rate. The COVID-19 pandemic made occupational health disparities for small businesses more visible and created an unprecedented financial burden, particularly for those located in communities of color. In part, communities of color experienced disproportionate mortality and morbidity rates from COVID-19 due to their increased exposure. The COVID-19 pandemic has prompted the public to reflect on risks daily. Risk perception is a critical factor influencing how risk gets communicated and perceived by individuals, groups, and communities. This study explores competing risk perceptions regarding COVID-19, economic impacts, vaccination, and disinfectant exposures of workers at beauty salons and auto shops in Tucson, Arizona, using a perceived risk score measured on a scale of 1–10, with higher scores indicating more perceived risk. The primary differences between respondents at beauty salons and auto shops regarding their perceived risks of COVID-19 vaccination were between the vaccinated and unvaccinated. For every group except the unvaccinated, the perceived risk score of getting the COVID-19 vaccine was low, and the score of not getting the COVID-19 vaccine was high. Study participants in different demographic groups ranked economic risk the highest compared to the other five categories: getting the COVID-19 vaccine, not getting the COVID-19 vaccine, COVID-19, disinfection, and general. A meaningful increase of four points in the perceived risk score of not getting the COVID-19 vaccine was associated with a 227% (95% CI: 27%, 740%) increase in the odds of being vaccinated. Analyzing these data collected during the coronavirus pandemic may provide insight into how to promote the health-protective behavior of high-risk workers and employers in the service sector during times of new novel threats (such as a future pandemic or crisis) and how they process competing risks.
Machine learning: A non-invasive prediction method for gastric cancer based on a survey of lifestyle behaviors
Authors: Jiang Siqing , Gao Haojun , He Jiajin , Shi Jiaqi , Tong Yuling , Wu Jian
Published: August 2022

Gastric cancer remains an enormous threat to human health. It is extremely significant to make a clear diagnosis and timely treatment of gastrointestinal tumors. The traditional diagnosis method (endoscope, surgery, and pathological tissue extraction) of gastric cancer is usually invasive, expensive, and time-consuming. The machine learning method is fast and low-cost, which breaks through the limitations of the traditional methods as we can apply the machine learning method to diagnose gastric cancer. This work aims to construct a cheap, non-invasive, rapid, and high-precision gastric cancer diagnostic model using personal behavioral lifestyles and non-invasive characteristics. A retrospective study was implemented on 3,630 participants. The developed models (extreme gradient boosting, decision tree, random forest, and logistic regression) were evaluated by cross-validation and the generalization ability in our test set. We found that the model developed using fingerprints based on the extreme gradient boosting (XGBoost) algorithm produced better results compared with the other models. The overall accuracy of which test set was 85.7%, AUC was 89.6%, sensitivity 78.7%, specificity 76.9%, and positive predictive values 73.8%, verifying that the proposed model has significant medical value and good application prospects.
The design and techno economic analysis of a succinic acid production facility
Authors: Tomczyk Sarah , Ozturk Serdar , Wawrzyniak Thomas , Tessman Monica , Ehrlich Christopher , Shaikh Faisal
Published: August 2022

Succinic acid is an industrially important commodity chemical that acts as a precursor to numerous other chemicals. This article explores an alternative biochemical route (as opposed to the traditional route from petroleum), by modeling a succinic acid production plant using Actinobacillus succinogenes, to convert the renewable sugars of corn stover feedstock. The model developed with SuperPro Designer v9.0 was used to evaluate the feasibility of this approach. This design is on par with the throughput of currentlarge scale manufacturers, by achieving an annual production rate of 11.5 US kilotons of succinic acid. The plant's economic standing is very attractive with a payback time of just under 5 years and return on investment of 20.4%. This article shows a facility design that maximizes profitability for a feasible and sustainable solution for bio-based succinic acid production.
The contemporary design of endovascular aneurysm stent-graft materials: PTFE versus polyester
Authors: Hynes Niamh , Acharya Yogesh , Sultan Sherif
Published: August 2022

Endovascular aneurysm repair of the abdominal aorta (EVAR) and of the thoracic aorta (TEVAR) have revolutionised therapeutic strategies in the management of aortic pathology, and endovascular repair is now an established and attractive alternative to open surgical repair (OSR) due to its superior short-term safety profile. However, opinions are divided regarding its long-term cost-effectiveness, which is reflected in the controversial NICE guidelines on abdominal aortic aneurysm (AAA) repair published in 2018, which advised against EVAR for elective aortic repair due to high secondary intervention rates and resultant associated costs. There is no doubt that OSR continues to have a valuable role to play in aortic repair, but it is not universally applicable, especially in older and sicker patients. Therefore, we should not dismiss EVAR and TEVAR without examining the reasons for long-term failure, and the most obvious starting point is stent graft material properties. Polytetrafluoroethylene (PTFE) and polyester are the two most common stent-graft materials; however, there has been no objective comparison of PTFE and polyester stent-graft post-procedural outcomes in EVAR and TEVAR, or even OSR. This lack of definitive data on different stent-graft materials and their configuration necessitates a comprehensive review to elucidate the post-procedural outcome in terms of endograft failure, cardiovascular events, and aortic-related mortality and morbidity.
Gender and Racial Disparity Among Liver Transplantation Professionals: Report of a Global Survey
Authors: Aguilera Victoria , Andacoglu Oya , Francoz Claire , Berlakovich Gabriela , Pai Sher-Lu , Adelmann Dieter , Ghosh Simantika , Lunsford Keri E. , Montenovo Martin , Mrzljak Anna , Scalera Irene , Xie Qinfen , Becchetti Chiara , Berenguer Marina , Selzner Nazia
Published: August 2022

Equality, diversity, and inclusion (EDI) are fundamental principles. Little is known about the pattern of practice and perceptions of EDI among liver transplant (LT) providers. International Liver Transplant Society (ILTS) EDI Committee survey around topics related to discrimination, mentorship, and gender. Answers were collected and analyzed anonymously. Worldwide female leadership was also queried via publicly available data. The survey was e-mailed to 1312 ILTS members, 199 responses (40.7% female) were collected from 38 countries (15.2% response rate). Almost half were surgeons (45.7%), 27.6% hepatologists and 26.6% anesthetists. Among 856 LT programs worldwide, 8.2% of leadership positions were held by females, and 22% of division chiefs were female across all specialties. Sixty-eight of respondents (34.7%) reported some form of discrimination during training or at their current position, presumably related to gender/sexual orientation (20.6%), race/country of origin (25.2%) and others (7.1%). Less than half (43.7%) received mentorship when discrimination occurred. An association between female responses and discrimination, differences in compensation, and job promotion was observed. This survey reveals alarmingly high rate of experience with racial and gender disparity, lack of mentorship, and very low rates of female leadership in the LT field and calls to action to equity and inclusion.
Effects of Controlled Release Urea Formula and Conventional Urea Ratio on Grain Yield and Nitrogen Use Efficiency of Direct-Seeded Rice
Authors: Cheng Shuang , Xing Zhipeng , Tian Chao , Li Shaoping , Tian Jinyu , Liu Qiuyuan , Hu Yajie , Guo Baowei , Hu Qun , Wei Haiyan , Gao Hui , Zhang Hongcheng
Published: August 2022

A one-off application of bulk blend urea (BBU), which includes a controlled release urea formula and conventional urea, has been recommended to simplify fertilisation management for direct-seeded rice. However, the effects of different basal application ratios of controlled-release urea formula and conventional urea on yield and nitrogen (N) use efficiency remain unknown in direct-seeded rice. This study set up three BBU treatments in which the controlled-release urea formula provided 50% (BBU1), 60% (BBU2), and 70% (BBU3) of the total N. This study measured their effects on grain yield and N use efficiency of direct-seeded rice. Split fertilisation with conventional urea was used as the control (CK). The study concluded four key points: (i) the grain yield of direct-seeded rice decreased as the proportion of controlled-release urea formula increased, (ii) BBU1 increased grain yields by 8.1–8.6% and 10.2–10.6% compared to BBU2 and BBU3, respectively, as well as a greater number of panicles and spikelets per m2, and post-anthesis dry matter accumulation, (iii) the N recovery efficiency and N agronomic efficiency of BBU1 were significantly higher than those of BBU2 and BBU3 treatments, and the nitrogen accumulation was also found to be more, and (iv) compared with the CK, BBU1 achieved considerable grain yield and nitrogen use efficiency while reducing the amount of fertilisation. In conclusion, the appropriate reduction of the basal application ratio of the controlled-release urea formula for direct-seeded rice increased grain yield and nitrogen use efficiency.
Seed-Soaking with Melatonin for the Improvement of Seed Germination, Seedling Growth, and the Antioxidant Defense System under Flooding Stress
Authors: Zeng Hongli , Liu Minghao , Wang Xin , Liu Ling , Wu Huiyi , Chen Xuan , Wang Haodong , Shen Quansheng , Chen Guanghui , Wang Yue
Published: August 2022

Flooding is the main cause of inhibited seed germination and seedling growth during the direct seeding of rice. As a growth-regulating hormone, melatonin plays an important role in promoting seed germination and enhancing plant stress resistance. However, there are still many unknown mechanisms related to the exogenous-melatonin-mediated regulation of submergence tolerance during seed germination. To overcome these challenges, this study investigated the effects of seed-soaking with different melatonin concentrations on the germination and physiological characteristics of rice seeds over different flooding times. The results showed that the exogenous administration of 100 μM of melatonin significantly improved the germination potential, germination rate, germination index, and vigor index of seeds and increased the size of the aboveground and underground biomass. By increasing the activities of superoxide dismutase (SOD) and peroxidase (POD) in shoots and roots, and reducing the content of malondialdehyde (MDA), the 100 μM melatonin alleviated the damage of rice seeds under flooding stress. The gray relational grade between the root MDA content and the melatonin seed-soaking treatment was the highest, and this was used to evaluate the effect of melatonin in alleviating flooding stress. A two-factor analysis of variance showed that the flooding stress treatment and the melatonin treatment had more significant effects on rice seed germination than the flooding and melatonin interaction treatments (p < 0.01). The optimal number of days for rice seeds to resist flooding stress was two, and the optimal concentration for the melatonin seed-soaking treatment was 100 μM. In sum, a 100 μM melatonin seed-soaking treatment can effectively alleviate the damage of flooding stress on rice seeds and promote the growth and development of seedlings. This study provides the theoretical basis for a light and simple cultivation technique for the direct seeding of rice.
Synthesis and Antioxidant Properties of HeteroBisNitrones Derived from Benzene Dicarbaldehydes
Authors: Diez-Iriepa Daniel , Iriepa Isabel , López-Muñoz Francisco , Marco-Contelles José , Hadjipavlou-Litina Dimitra
Published: August 2022

We report herein the synthesis and antioxidant profile of nine novel heterobisnitrones (hBNs) as new α-phenyl-tert-butylnitrone (PBN) analogues. The synthesized hBNs 1–9 were evaluated for their antioxidant activity using different in vitro techniques, while they were also tested as inhibitors of soybean LOX, as an indication of their anti-inflammatory effect. Nitrone hBN9 is the most potent antioxidant presenting higher anti-lipid peroxidation and hydroxyl radicals scavenging activities as well as higher lipoxygenase inhibition. In silico calculations reveal that hBN9 follows Lipinski’s rule of five and that the molecule is able to penetrate theoretically the brain. All these results led us to propose hBN9 as a new potent antioxidant nitrone.
Microwave-Assisted Deep Eutectic Solvent Extraction, Structural Characteristics, and Biological Functions of Polysaccharides from Sweet Tea (Lithocarpus litseifolius) Leaves
Authors: Wu Ding-Tao , Fu Meng-Xi , Guo Huan , Hu Yi-Chen , Zheng Xiao-Qin , Gan Ren-You , Zou Liang
Published: August 2022

The leaf of sweet tea (Lithocarpus litseifolius) is widely used as an edible and medicinal plant in China, which is rich in bioactive polysaccharides. In order to explore and promote the application of sweet tea polysaccharides in the functional food industry, the microwave-assisted deep eutectic solvent extraction (MDAE) of polysaccharides from sweet tea leaves was optimized, and the structural properties and biological functions of sweet tea polysaccharides prepared by MDAE (P-DM) were investigated and compared with that of hot water extraction (P-W). The maximum yield (4.16% ± 0.09%, w/w) of P-DM was obtained under the optimal extraction conditions (extraction time of 11.0 min, extraction power of 576.0 W, water content in deep eutectic solvent of 21.0%, and liquid–solid ratio of 29.0 mL/g). Additionally, P-DM and P-W possessed similar constituent monosaccharides and glycosidic bonds, and the homogalacturonan (HG) and arabinogalactan (AG) might exist in both P-DM and P-W. Notably, the lower molecular weight, higher content of total uronic acids, and higher content of conjugated polyphenols were observed in P-DW compared to P-W, which might contribute to its much stronger in vitro antioxidant, anti-diabetic, antiglycation, and prebiotic effects. Besides, both P-DW and P-W exhibited remarkable in vitro immunostimulatory effects. The findings from the present study indicate that the MDAE has good potential to be used for efficient extraction of bioactive polysaccharides from sweet tea leaves and P-DM can be developed as functional food ingredients in the food industry.
Micro-Encapsulation of Phytochemicals in Passion Fruit Peel Waste Generated on an Organic Farm: Effect of Carriers on the Quality of Encapsulated Powders and Potential for Value-Addition
Authors: Kobo Gift Kabelo , Kaseke Tafadzwa , Fawole Olaniyi Amos
Published: August 2022

The passion (Passiflora edulis Sims) fruit peel is rich in phenolics and other bioactive compounds and has great potential as a natural food preservative. The present study investigated the value-adding potential of passion fruit peel waste generated on an organic farm. The effect of carriers in encapsulating the peel extract to develop a polyphenolic-rich powder was investigated. The passion fruit peel extracts were prepared using 70% ethanol (1:10 w/v), and encapsulated using waxy starch (WS), gum arabic (GA), and maltodextrin (MT) before freeze-drying. The effects of carriers on the passion fruit peel powder (PFPP) production yield, physicochemical, rheological, phytochemical, and antioxidant properties were investigated. GA-and MT-encapsulated powders had better physical, phytochemical, and antioxidant properties, including yield, total soluble solids, solubility, bulk density, total phenolic content, and ferric reducing antioxidant powder. A total of 18 metabolites, including phenolic acids (10), flavonoids (6), and stilbenes (2), were tentatively identified in all the PFPP samples, with WS exhibiting a higher concentration of the compounds compared to GA and MT. Our results indicated that no single carrier was associated with all the quality attributes; therefore, better results could be produced by compositing these carriers. Nonetheless, our results highlight the potential of passion fruit peels as a source of polyphenols and functional ingredient in formulating natural food additives.
Tolerance Assessment of Atractylodes macrocephala Polysaccharide in the Diet of Largemouth Bass (Micropterus salmoides)
Authors: Dong Bo , Wu Liyun , Chen Qiaozhen , Xu Wenjie , Li Dinggang , Han Dong , Zhu Xiaoming , Liu Haokun , Yang Yunxia , Xie Shouqi , Jin Junyan
Published: August 2022

Atractylodes macrocephala polysaccharide (AMP) can enhance antioxidant defense and anti-inflammation, as the tolerance levels of AMP in aquaculture is important for additive utilization. However, the tolerance dose of AMP is unknown. We assess the tolerance levels of AMP in juvenile largemouth bass (3.38 ± 0.11 g) by feeding them a 0, 400, 4000, or 8000 mg/kg AMP supplemented diet for 10 weeks. The 400 mg/kg AMP dose increased growth performance. The Nrf2/Keap1 signaling pathway was activated, as indicated by Keap1 and Nrf2 protein levels in the liver. Enhanced activity of antioxidant enzymes (SOD, GPx), together with increased mRNA levels of antioxidant genes (sod, gpx) and decreased accumulation of reactive oxygen species (ROS) and MDA, was found in the liver, implying the antioxidant effect of AMP. Nutrient absorption was enhanced by AMP, as reflected by the increased length of intestinal villi and microvilli. However, 4000 and 8000 mg/kg AMP induced oxidant stress, as indicated by increased plasma ALT and AST content and decreased mRNA levels of antioxidant genes (sod, gpx) in the liver and intestinal tissues. Inflammatory reactions were also induced by high doses of AMP, as reflected by enhanced levels of pro-inflammatory cytokines (tnfα, nfκb) in the liver, intestinal, and kidney tissues and inhibited levels of anti-inflammatory cytokines (tgfβ, iκb). Histological analysis reveals inflammatory cell infiltration and tissue damage. Thus, the safe tolerance margin of AMP supplement for largemouth bass was 400–4000 mg/kg.
NRF2 Regulates Cystathionine Gamma-Lyase Expression and Activity in Primary Airway Epithelial Cells Infected with Respiratory Syncytial Virus
Authors: Jamaluddin Mohammad , Haas de Mello Aline , Tapryal Nisha , Hazra Tapas K. , Garofalo Roberto P. , Casola Antonella
Published: August 2022

Cystathionine-y-lyase (CSE) is a critical enzyme for hydrogen sulfide (H2S) biosynthesis and plays a key role in respiratory syncytial virus (RSV) pathogenesis. The transcription factor NRF2 is the master regulator of cytoprotective and antioxidant gene expression, and is degraded during RSV infection. While some evidence supports the role of NRF2 in CSE gene transcription, its role in CSE expression in airway epithelial cells is not known. Here, we show that RSV infection decreased CSE expression and activity in primary small airway epithelial (SAE) cells, while treatment with tert-butylhydroquinone (tBHQ), an NRF2 inducer, led to an increase of both. Using reporter gene assays, we identified an NRF2 response element required for the NRF2 inducible expression of the CSE promoter. Electrophoretic mobility shift assays demonstrated inducible specific NRF2 binding to the DNA probe corresponding to the putative CSE promoter NRF2 binding sequence. Using chromatin immunoprecipitation assays, we found a 50% reduction in NRF2 binding to the endogenous CSE proximal promoter in SAE cells infected with RSV, and increased binding in cells stimulated with tBHQ. Our results support the hypothesis that NRF2 regulates CSE gene transcription in airway epithelial cells, and that RSV-induced NRF2 degradation likely accounts for the observed reduced CSE expression and activity.
A Modeling Method of Agents and SOA in Advanced Avionics System Based on AADL
Authors: Deng Pingyu , Zhou Qing , An Dong , Wang Shihai , Li Kui
Published: August 2022

The modeling method of agents and service-oriented architecture (SOA) in avionics systems describes agents and SOA in avionics systems with models. To our knowledge, however, the current modeling methods cannot describe the behavior of agents and SOA accurately and do not fit well with the existing avionics system models. This paper addresses the above problems by presenting a modeling method based on architecture analysis and design language (AADL). In this method, the working states of agents are described by the mode components, with the working process being triggered by the input of agents; and the services are described by the process component. The application of the software system is described by the system components that contain several process components. Moreover, different modes of the system are used to describe different applications, and the transitions of application are triggered by specific application requests. Software architecture of an avionics system is modeled by the proposed method. This case demonstrates that the proposed method can accurately describe how agents and SOA work in a new way and fit well with the existing avionics system models.
The Effectiveness of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis, Familial Pulmonary Fibrosis and Progressive Fibrosing Interstitial Lung Diseases: A Real-World Study
Authors: Cameli Paolo , Alonzi Valerio , d’Alessandro Miriana , Bergantini Laura , Pordon Elena , Guerrieri Marco , Refini Rosa Metella , Sestini Piersante , Bargagli Elena
Published: August 2022

Background: Nintedanib is an oral multitarget tyrosine kinase inhibitor approved for the treatment of patients with idiopathic pulmonary fibrosis (IPF). Recent evidence demonstrated that nintedanib reduced functional disease progression also in subjects with non-IPF progressive fibrosing interstitial lung disease (PF-ILD). However, real-life data on the effectiveness of nintedanib in PF-ILD and familial pulmonary fibrosis (FPF) are lacking. Methods: this retrospective monocentric study enrolled 197 patients affected with IPF, PF-ILD and FPF treated with nintedanib at the Referral Centre of Siena from 2014 to 2021. Pulmonary functional tests and survival data were collected throughout the observation period for the evaluation of mortality and disease progression outcomes. Results: nintedanib treatment significantly reduced the FVC decline rate in IPF and PF-ILD subgroups, but not in FPF subjects. No significant differences were observed among the subgroups in terms of survival, which appeared to be influenced by gender and impaired lung function (FVC < 70% of predicted value). Concerning disease progression rate, a diagnosis of FPF is associated with more pronounced FVC decline despite nintedanib treatment. Conclusions: our research studies the effectiveness and safety of nintedanib in reducing functional disease progression of IPF and PF-ILD. FPF appeared to be less responsive to nintedanib, even though no differences were observed in terms of survival.
Mixed-Phenotype Acute Leukemia: Clinical Diagnosis and Therapeutic Strategies
Authors: George Binsah S. , Yohannan Binoy , Gonzalez Anneliese , Rios Adan
Published: August 2022

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. The prognosis of adults and children with MPAL varies; this justifies modulating the intensity of therapy, including the use of allo-sct as a consolidation strategy.
Interleukin-4 Receptor Targeting Peptide Decorated Extracellular Vesicles as a Platform for In Vivo Drug Delivery to Thyroid Cancer
Authors: Gangadaran Prakash , Gunassekaran Gowri Rangaswamy , Rajendran Ramya Lakshmi , Oh Ji Min , Vadevoo Sri Murugan Poongkavithai , Lee Ho Won , Hong Chae Moon , Lee Byungheon , Lee Jaetae , Ahn Byeong-Cheol
Published: August 2022

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been demonstrated to deliver therapeutic drugs in preclinical studies. However, their use is limited, as they lack the ability to specifically deliver drugs to tumor tissues in vivo. In the present study, we propose the use of a targeting peptide, IL-4R-binding peptide (IL4RPep-1), to specifically deliver intravenously (i.v.) infused EVs to thyroid tumors. In vivo, a xenograft tumor model was treated with either the control peptide (NSSSVDK) or IL4RPep-1-Flamma; mice were fluorescently imaged (FLI) using an in vivo imaging system at 0–3 h post-treatment. EVs (labeled with DiD dye) were conjugated with IL4RPep-1 through a DOPE-NHS linker and administered to mice intravenously. FLI was performed 0–24 h post-injection, and the animals were sacrificed for further experiments. The morphology and size of EVs, the presence of EV markers such as CD63 and ALIX, and the absence of the markers GM130 and Cyto-C were confirmed. In vivo, FLI indicated an accumulation of i.v. injected IL4RPep-1-Flamma at the tumor site 90 min post-injection. No accumulation of NSSSVDK-Flamma was detected. In vivo, IL4RPep-1-EVs targeted the Cal-62 tumor 2 h post-injection. NSSSVDK-EVs were not even detected in the tumor 24 h post-injection. The quantification of FLI showed a significant accumulation of MSC-EVs in the tumor 2 h, 3 h, and 24 h post-injection. Furthermore, ex vivo imaging and an IF analysis confirmed the in vivo findings. Our results demonstrate the use of the IL4RPep-1 peptide as a targeting moiety of EVs for IL-4R-expressing anaplastic thyroid tumors.
Protein Kinase CK2 and Its Potential Role as a Therapeutic Target in Huntington’s Disease
Authors: White Angel , McGlone Anna , Gomez-Pastor Rocio
Published: August 2022

Huntington’s Disease (HD) is a devastating neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene, for which no disease modifying therapies are currently available. Much of the recent research has focused on developing therapies to directly lower HTT expression, and while promising, these therapies have presented several challenges regarding administration and efficacy. Another promising therapeutic approach is the modulation of HTT post-translational modifications (PTMs) that are dysregulated in disease and have shown to play a key role in HTT toxicity. Among all PTMs, modulation of HTT phosphorylation has been proposed as an attractive therapeutic option due to the possibility of orally administering specific kinase effectors. One of the kinases described to participate in HTT phosphorylation is Protein Kinase CK2. CK2 has recently emerged as a target for the treatment of several neurological and psychiatric disorders, although its role in HD remains controversial. While pharmacological studies in vitro inhibiting CK2 resulted in reduced HTT phosphorylation and increased toxicity, genetic approaches in mouse models of HD have provided beneficial effects. In this review we discuss potential therapeutic approaches related to the manipulation of HTT-PTMs with special emphasis on the role of CK2 as a therapeutic target in HD.
The Acid Ceramidase Is a SARS-CoV-2 Host Factor
Authors: Geiger Nina , Kersting Louise , Schlegel Jan , Stelz Linda , Fähr Sofie , Diesendorf Viktoria , Roll Valeria , Sostmann Marie , König Eva-Maria , Reinhard Sebastian , Brenner Daniela , Schneider-Schaulies Sibylle , Sauer Markus , Seibel Jürgen , Bodem Jochen
Published: August 2022

SARS-CoV-2 variants such as the delta or omicron variants, with higher transmission rates, accelerated the global COVID-19 pandemic. Thus, novel therapeutic strategies need to be deployed. The inhibition of acid sphingomyelinase (ASM), interfering with viral entry by fluoxetine was reported. Here, we described the acid ceramidase as an additional target of fluoxetine. To discover these effects, we synthesized an ASM-independent fluoxetine derivative, AKS466. High-resolution SARS-CoV-2–RNA FISH and RTqPCR analyses demonstrate that AKS466 down-regulates viral gene expression. It is shown that SARS-CoV-2 deacidifies the lysosomal pH using the ORF3 protein. However, treatment with AKS488 or fluoxetine lowers the lysosomal pH. Our biochemical results show that AKS466 localizes to the endo-lysosomal replication compartments of infected cells, and demonstrate the enrichment of the viral genomic, minus-stranded RNA and mRNAs there. Both fluoxetine and AKS466 inhibit the acid ceramidase activity, cause endo-lysosomal ceramide elevation, and interfere with viral replication. Furthermore, Ceranib-2, a specific acid ceramidase inhibitor, reduces SARS-CoV-2 replication and, most importantly, the exogenous supplementation of C6-ceramide interferes with viral replication. These results support the hypotheses that the acid ceramidase is a SARS-CoV-2 host factor.
Maternal Anxiety Associated with Nocturnal Childhood Enuresis
Authors: Quiroz-Guerrero Javier , Ortega-Pardo Alejandra , Maldonado-Valadez Rafael Edgardo , García-Díaz de León Raúl , Mercado-Villareal Lorena , Rodea-Montero Edel Rafael
Published: August 2022

Introduction: Nocturnal enuresis is a common problem affecting 20% of 5-year-old children; its prevalence decreases with age. Nocturnal bedwetting in children younger than 5 is generally accepted by parents and society, but the expectation of parents is that children will achieve a higher degree of responsibility and increased control with age. Some studies have identified maternal distress as a factor associated with childhood urinary incontinence; specifically, maternal stress, maternal depression, and maternal anxiety. The aim of this study was to compare the degree of anxiety (trait and state) among mothers of children with nocturnal enuresis and mothers of healthy children. Methods: This was a prospective, cross-sectional, comparative study including two groups: a control group of 25 mothers of healthy children from open population, and an enuresis group of 25 mothers of children with nocturnal enuresis of the pediatric urology clinic of a third-level Mexican Hospital. STAI-T and STAI-S tests were performed and assessed blindly. Quantitative variables were compared using the Mann–Whitney U test, and qualitative determinations using a chi-square test or Fischer’s exact test. Results: The STAI-S and STAI-T tests results identified 14 (56%) mothers of enuretic children with moderate-to-severe trait anxiety versus 4 (16%) mothers from the control group and moderate-to-severe state anxiety in 23 (92%) of the mothers of enuretic children compared to 7 (28%) control-group mothers. The anxiety scores were significantly higher for the enuresis group for both tests: STAI-T: 53.00 ± 8.39 versus 41.52 ± 9.61 (p < 0.001) and STAI-S: 56.48 ± 6.83 versus 43.84 ± 10.57 (p < 0.001). Conclusion: Mothers of children with nocturnal enuresis present state anxiety ranging from moderate to severe. In clinical practice, our results indicate that the transitory emotion experienced by mothers of enuretic children cannot be neglected in an enuresis treatment program, state anxiety needs to be evaluated, and psychological interventions need to be implemented.
Multifunctionality of Clausena harmandiana Extract and Its Active Constituents against Alzheimer’s Disease
Authors: Boonyarat Chantana , Yenjai Chavi , Monthakantirat Orawan , Kaewamatawong Rawiwun , Poonsawas Pattaporn , Wangboonskul Jinda , Chaiwiwatrakul Suchada , Waiwut Pornthip
Published: August 2022

This study was designed to investigate the effects of the root-bark extract of Clausena harmandiana (CH) and its active constituents (nordentatin and 7-methoxyheptaphylline) on pharmacological activities regarding selected targets associated with AD, namely, its antioxidant activity, inhibition of Aβ aggregation, acetylcholinesterase (AChE) activity, and neuroprotective effects. The effect of the CH extract on the cognitive impairment induced by scopolamine was also evaluated in mice. The effects of the CH extract and its active constituents on radical scavenging, Aβ aggregation, and AChE activity were investigated with a 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assay, a thioflavin-T assay, and Ellman’s method. The neuroprotective effects of the extract against hydrogen-peroxide and Aβ toxicity were evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. In addition, the effects on cognitive impairment induced by scopolamine in mice were evaluated using Morris-water-maze and modified-Y-maze test models. The results of the present study demonstrate that the root-bark extract of CH shows multimodal actions relevant to the AD pathological cascade, including antioxidant effects, the inhibition of Aβ aggregation, the inhibition of AChE function, and neuroprotection against oxidative stress and Aβ toxicity. The extracts could improve both the short- and long-term memory deficits induced by scopolamine in mice.
Human Exposure Influence Analysis for Wireless Electric Vehicle Battery Charging
Authors: El-Shahat Adel , Danjuma Joshua , Abdelaziz Almoataz Y. , Abdel Aleem Shady H. E.
Published: August 2022

Wireless charging schemes aim to counter some drawbacks of electric vehicles’ wired charging, such as the fact that it does not encourage mobility, leads to safety issues regarding high voltage cables, power adapters high cost, and has more battery waste by companies. In this paper, a comparative study of wireless power transfer multiple coil geometries is performed to analyze the efficiency, coupling coefficient, mutual inductance, and magnetic flux density production for each geometry. Results show that coil geometry, current excitation, and shielding techniques within the Wireless Electric Vehicle Charging (WEVC) system substantially influence magnetic flux leakage. In addition, the paper proposes an analytical framework for a WEVC scheme via electromagnetic resonance coupling. Safety considerations of the WEVC system, including the effects on humans, are investigated in several scenarios based on the relative location of the human while EV charging is conducted as the leading paper’s goal. The exposure measurements are performed across various radial distances from the coils using 3-D FEA ANSYS Maxwell Software (American technology company, Pennsylvania, United States). The analysis shows that WEVC systems can achieve high power transfer, resulting in increased magnetic flux leakage around the coils. The safe distance for humans and animals during the charging sequence is attained from research results. For instance, in the 120 mm spiral coil, 120 mm square coil, and 600 mm spiral coil operating at 1 A, excitation, the SAR levels are under the threshold of 700 mm away from the coils. For the 600 mm spiral coil excited at 8 A, the SAR levels fall under the threshold at 900 mm away from the coils. When shielding is utilized, the safe distance is improved by up to 350 mm. Considering the regulations of the Non-Ionizing Radiation Protection (ICNIRP) standards, 600 mm is a safe distance away from the coils, and, vertically, anywhere past 300 mm is safe for humans.
Deep Transfer Network with Multi-Space Dynamic Distribution Adaptation for Bearing Fault Diagnosis
Authors: Zheng Xiaorong , Gu Zhaojian , Liu Caiming , Jiang Jiahao , He Zhiwei , Gao Mingyu
Published: August 2022

Domain adaptation-based bearing fault diagnosis methods have recently received high attention. However, the extracted features in these methods fail to adequately represent fault information due to the versatility of the work scenario. Moreover, most existing adaptive methods attempt to align the feature space of domains by calculating the sum of marginal distribution distance and conditional distribution distance, without considering variable cross-domain diagnostic scenarios that provide significant cues for fault diagnosis. To address the above problems, we propose a deep convolutional multi-space dynamic distribution adaptation (DCMSDA) model, which consists of two core components: two feature extraction modules and a dynamic distribution adaptation module. Technically, a multi-space structure is proposed in the feature extraction module to fully extract fault features of the marginal distribution and conditional distribution. In addition, the dynamic distribution adaptation module utilizes different metrics to capture distribution discrepancies, as well as an adaptive coefficient to dynamically measure the alignment proportion in complex cross-domain scenarios. This study compares our method with other advanced methods, in detail. The experimental results show that the proposed method has excellent diagnosis performance and generalization performance. Furthermore, the results further demonstrate the effectiveness of each transfer module proposed in our model.
Pressure Injury Link to Entropy of Abdominal Temperature
Authors: Padhye Nikhil , Rios Denise , Fay Vaunette , Hanneman Sandra K.
Published: August 2022

This study examined the association between pressure injuries and complexity of abdominal temperature measured in residents of a nursing facility. The temperature served as a proxy measure for skin thermoregulation. Refined multiscale sample entropy and bubble entropy were used to measure the irregularity of the temperature time series measured over two days at 1-min intervals. Robust summary measures were derived for the multiscale entropies and used in predictive models for pressure injuries that were built with adaptive lasso regression and neural networks. Both types of entropies were lower in the group of participants with pressure injuries (n=11) relative to the group of non-injured participants (n=15). This was generally true at the longer temporal scales, with the effect peaking at scale τ=22 min for sample entropy and τ=23 min for bubble entropy. Predictive models for pressure injury on the basis of refined multiscale sample entropy and bubble entropy yielded 96% accuracy, outperforming predictions based on any single measure of entropy. Combining entropy measures with a widely used risk assessment score led to the best prediction accuracy. Complexity of the abdominal temperature series could therefore serve as an indicator of risk of pressure injury.
Current Interventions for the Digital Onboarding of First-Year Students in Higher Education Institutions: A Scoping Review
Authors: Schilling Hannes , Wittner Britta , Kauffeld Simone
Published: August 2022

Every year, students around the globe embark upon their higher education journey, making the onboarding of these students a critical task for colleges and universities. Combined with the growth in distance learning and the rapid development in technologies, the onboarding process occurs increasingly in the digital setting. For this reason, the objective of this scoping review was to report and map interventions, which are used in digital onboarding of first-year students in higher education institutions and explore the digital settings that characterized these interventions. The PRISMA-ScR Guidelines and the JBI Manual for Evidence Synthesis guided this investigation, which included researching four databases and screening the resulting titles and abstracts to identify the 17 sources of evidence included in the final analysis. According to our results, digital and virtual onboarding interventions were categorized into four onboarding dimensions: information interventions, socialization interventions, counseling interventions, and self-study interventions. Examples of the purposes and outcomes of these onboarding interventions included the transfer of information and the socialization of incoming students. Of the five onboarding settings that were also identified in the categorization, telecommunication software and virtual environments predominated. An independently developed onboarding tool could combine the identified onboarding settings and dimensions in the future.
AR4FSM: Mobile Augmented Reality Application in Engineering Education for Finite-State Machine Understanding
Authors: Nadeem Muhammad , Lal Mayank , Cen Jiaming , Sharsheer Mohammad
Published: August 2022

Students in the twenty-first century are accustomed to using technology in all aspects of their lives and have never known a world without it; the classroom is no exception. Augmented reality (AR) is a technology that bridges the virtual and physical worlds to make learning more engaging and enjoyable. In this paper, we present a mobile application aimed at novice learners that makes use of technology for the teaching and learning of computer system engineering concepts. Currently, students typically learn about finite-state machine (FSM) concepts from lectures, tutorials, and practical hands-on experience combined with commercial timing simulation tools. We aimed to enhance these traditional, lecture-based instruction and information delivery methods. We developed an AR-based FSM visualization tool called AR4FSM to help students more easily grasp concepts through immersion and natural interaction with an FSM. We used a blend of multimedia information, such as text, images, sound, and animations superimposed on real-world-state machine diagrams, presenting the information in an interactive and compelling way. An experiment with 60 students showed that the app was perceived positively by the students and helped to deliver FSM-related concepts in a way that was easier to understand than traditional, lecture-based teaching methods. This instruction methodology not only engaged the students but also motivated them to learn the material. The findings of this study have inspired us to use this application to teach FSM topics in the classroom.