bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Bariatric Surgery on Metabolic Syndrome, Framingham Risk Scores and Thyroid Function during One-Year Follow-Up: A Saudi Retrospective Study
Authors: Alamro Nuha , Azhri Afnan S. , Almuqati Asma , Azzeh Firas , Azhar Wedad , Qadhi Alaa , Almohmadi Najlaa H. , Abusudah Wafaa F. , Ghafouri Khloud
Published: December 2022

Bariatric surgery (BS) has been demonstrated to achieve sustained weight loss with significant metabolic improvement, including a reduction in cardiovascular disease and diabetes. The aim of this retrospective study is to measure the effect of BS on the Framingham risk score (FRS) and metabolic syndrome (MetS) among patients who underwent bariatric surgery. Additionally, we determine the effect of BS on thyroid-stimulating hormone (TSH) among euthyroid obese patients. A retrospective follow-up study was conducted at King Abdullah Medical City, Makkah, Saudi Arabia. A total of 160 patients underwent BS and completed one-year follow-up visits. Medical history, anthropometric, biochemical, and hormonal parameters were evaluated at baseline and 3–12 months after BS. The International Diabetes Federation (IDF) criteria were used to diagnose MetS. There was a significant decrease in systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (Hba1c), TSH, low-density lipoprotein (LDL), triglycerides, and total cholesterol (p < 0.001). A significant decrease was seen in MetS, BMI, FRS, SBP, DBP, Hba1c, LDL, triglycerides, cholesterol, and liver enzymes, with a significant increase in high-density lipoprotein levels 12 months postoperatively (p < 0.001). At 12 months, the prevalence of MetS, DM, and HTN and the FRS significantly decreased from 72.5%, 43.1%, 78.1%, and 11.4 to 16.3%, 9.4%, 22.5%, and 5.4, respectively. In addition to achieving substantial weight loss, BS improves MetS prevalence and cardiovascular risk profiles.
Greenhouse Management for Better Vegetable Quality, Higher Nutrient Use Efficiency, and Healthier Soil
Authors: Li Xun , Hu Xiaohui , Song Shiwei , Sun Da
Published: December 2022

Greenhouse cultivation provides an artificially controlled environment for the off-season production of vegetables, and has played an increasingly important role in agriculture production systems in recent decades [...]
Aquatic Macroinvertebrate Community Structure along a Continuum in a Spring Dominated River, Missouri, USA
Authors: Heth Rachel L. S. , Bowles David E.
Published: December 2022

The Current River is a cold-water, thermally constant Missouri Ozark stream and is one of the few remaining free-flowing rivers in the U.S. The Current River’s baseflow is largely fed by hundreds of springs, which include five first-magnitude springs. Little attention has been given to the influence of spring inflows on river temperature and spring influence on biodiversity. The objectives of this study were to demonstrate how large springs affect river macroinvertebrate communities, and to explore the relationships among macroinvertebrate diversity and habitat variables to estimate spring influences on community structure and diversity. Aquatic macroinvertebrates were collected from 42 riffle/run habitats of the Current River main-stem, tributaries, and springs during the winter season. Samples at each site were collected using a Slack-Surber sampler for macroinvertebrates with additional habitat variables collected: substrate size, embeddedness, periphyton, filamentous green algae, vegetation, depth, current velocity, temperature, dissolved oxygen, specific conductance, and pH. Beta diversity analysis was performed on consecutive pairs of site taxa richness values using the Wilson–Shmida calculation to determine the impact of main-stem confluences with either tributaries or springs, and invertebrate community relationships were explored using nonmetric multidimensional scaling (NMDS). Water temperature and taxa richness exhibited similar patterns, with higher temperatures being associated with lower taxa richness. Downstream of each large-magnitude spring, taxa richness sharply decreased, while taxa richness increased downstream of tributaries. Beta diversity usually declined downstream of the confluences with springs, but increased downstream of the tributaries. Data from large springs were closely grouped in NMDS, while tributaries and main-stem sites were more widely scattered. These data indicate spring inputs produce more homogenous conditions in the main-stem river compared to more heterogenous conditions produced by tributary inputs. Macroinvertebrate diversity along the Current River also does not follow predictions from the river continuum concept, but rather diversity peaks are downstream of springs. Our data clearly demonstrate the strong influence of large springs on macroinvertebrate communities in the Current River.
Daily Streamflow Forecasting in Mountainous Catchment Using XGBoost, LightGBM and CatBoost
Authors: Szczepanek Robert
Published: December 2022

Streamflow forecasting in mountainous catchments is and will continue to be one of the important hydrological tasks. In recent years machine learning models are increasingly used for such forecasts. A direct comparison of the use of the three gradient boosting models (XGBoost, LightGBM and CatBoost) to forecast daily streamflow in mountainous catchment is our main contribution. As predictors we use daily precipitation, runoff at upstream gauge station and two-day preceding observations. All three algorithms are simple to implement in Python, fast and robust. Compared to deep machine learning models (like LSTM), they allow for easy interpretation of the significance of predictors. All tested models achieved Nash-Sutcliffe model efficiency (NSE) in the range of 0.85–0.89 and RMSE in the range of 6.8–7.8 m3s−1. A minimum of 12 years of training data series is required for such a result. The XGBoost did not turn out to be the best model for the daily streamflow forecast, although it is the most popular model. Using default model parameters, the best results were obtained with CatBoost. By optimizing the hyperparameters, the best forecast results were obtained by LightGBM. The differences between the model results are much smaller than the differences within the models themselves when suboptimal hyperparameters are used.
Evolutionary Game Research on Green Construction Considering Consumers’ Preference under Government Supervision
Authors: Geng Xiaoxiao , Lv Ling , Wang Yingchen , Sun Ran , Wang Xiangmei
Published: December 2022

Construction is closely related to people’s lives and public activities. With regard to issues of energy conservation, emission reduction, and sustainable development put forth, the word “green” is increasingly used in the construction industry. Green construction is an inevitable requirement for the sustainable development of the construction industry. In addition, the government regulation mechanism is also the key to the establishment and development of green construction. Thus, on the basis of evolutionary game theory, this paper constructs an evolutionary game model of developers, general contractors, and the government. Then, the evolutionary stability strategies under different conditions are discussed. Lastly, the evolution mechanism in the game process of the green construction system and the influence of relevant parameters on the evolution path of the game model are analyzed through numerical simulation. The results show that (1) when consumer preferences change, the evolutionary stability strategies also change. Consumer preference plays a positive role in the establishment and development of green construction, but a certain increase in consumer preference will lead to free-rider behavior. (2) The government’s control mechanism can not only effectively mobilize the enthusiasm of enterprises to participate but also effectively inhibit the free-rider behavior of enterprises; however, it cannot completely prevent the occurrence of free-rider behavior. (3) On the one hand, the government can advocate green consumption to promote the improvement of consumers’ green preferences; on the other hand, enterprises actively carry out technological innovation and equipment advances to enhance the likelihood that consumers will embrace green preferences to achieve the optimal ESS. This study not only provides good guidance for developers and general contractors to make optimal strategic choices under different consumers’ green preferences, but also provides a reference for the government to formulate reasonable regulatory policies. At the same time, it promotes the development of green construction and further promotes environmental protection.
The Association between Occupational Stress and Mental Health among Chinese Soccer Referees in the Early Stage of Reopening Soccer Matches during the COVID-19 Pandemic Outbreak: A Moderated Mediation Model
Authors: Liu Zongyu , Zhao Liangyu , Wang Shuzhen , Gao Yubo , Zhang Liguo
Published: December 2022

Background: The sudden and unpredictable changes caused by the COVID-19 pandemic are a serious threat to the occupational stress and mental health of referees worldwide, which has not attracted widespread attention. The mental health of football referees has a certain influence on their job satisfaction or the accuracy of judgments. Methods: This study constructed a moderated mediation model to explore the buffer factors between occupational stress and mental health in Chinese soccer referees in the early stage of reopening soccer matches during the COVID-19 pandemic outbreak. Data from 317 Chinese soccer referees (aged 19–45) were collected through an online questionnaire in September–October 2022. Occupational stress, mental health, job burnout and perceived social support were measured, and moderated mediation model was analyzed. Results: The results of this study showed that occupational stress was negatively correlated with mental health through the mediating effect of job burnout and the moderated effect of perceived social support after controlling for demographic variables. Specifically, the association between occupational stress and mental health was weaker when perceived social support was higher and stronger. Conclusions: The results demonstrate that job burnout and perceived social support played important roles in buffering the negative effects of occupational stress on the mental health of Chinese soccer referees in the early stage of reopening soccer matches during the COVID-19 pandemic outbreak. The findings provide implications for mental health interventions in soccer referees during the public health crises.
Polysubstance Use Patterns among Outpatients Undergoing Substance Use Disorder Treatment: A Latent Class Analysis
Authors: Bonfiglio Natale Salvatore , Portoghese Igor , Renati Roberta , Mascia Maria Lidia , Penna Maria Pietronilla
Published: December 2022

Substance Use Disorders (SUDs) pose significant challenges to both individuals and society at large. The primary focus of existing research with clinical SUD populations has been on individual substances, but research is required to better understand the profiles of individuals who use different substances simultaneously. The purpose of the current study was, therefore, to identify patterns of use among subjects (n = 1025) who reported using multiple substances by adopting a Latent Class Analysis (LCA) methodology. The Addiction Severity Index (ASI-lite) was included as a measure of substance misuse, we performed LCA to identify patterns of substance use through the administration of the ASI-Lite. Responses were collected from the following substances: alcohol, cannabis/cannabinoids, opioids and heroin, and cocaine. Results identified two latent classes: (1) alcohol use dominant, and (2) poly-abuser use dominants. Class 1 represented 60.0% of the sample and refers to individuals with the dominant use of alcohol, of those a higher proportion (47%) reported low-frequency use (1 to 7 days per month) and 26% reported a frequency of use of 24 to 30 days per month. Furthermore, 18% used alcohol in combination with cocaine. Class 2 represents 40.0% of the sample. This class is characterized by low-frequency and high-frequency users of several substances. The results obtained highlight the importance of deepening the study of the concomitant use of substances in individuals with SUDs to better understand the health risk of the combined use of two or more substances.
Delivering Digital Healthcare for Elderly: A Holistic Framework for the Adoption of Ambient Assisted Living
Authors: Almalki Manal , Alsulami Majid H. , Alshdadi Abdulrahman A. , Almuayqil Saleh N. , Alsaqer Mohammed S. , Atkins Anthony S. , Choukou Mohamed-Amine
Published: December 2022

Adoption of Ambient Assisted Living (AAL) technologies for geriatric healthcare is suboptimal. This study aims to present the AAL Adoption Diamond Framework, encompassing a set of key enablers/barriers as factors, and describe our approach to developing this framework. A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. SCOPUS, IEEE Xplore, PubMed, ProQuest, Science Direct, ACM Digital Library, SpringerLink, Wiley Online Library and grey literature were searched. Thematic analysis was performed to identify factors reported or perceived to be important for adopting AAL technologies. Of 3717 studies initially retrieved, 109 were thoroughly screened and 52 met our inclusion criteria. Nineteen unique technology adoption factors were identified. The most common factor was privacy (50%) whereas data accuracy and affordability were the least common factors (4%). The highest number of factors found per a given study was eleven whereas the average number of factors across all studies included in our sample was four (mean = 3.9). We formed an AAL technology adoption framework based on the retrieved information and named it the AAL Adoption Diamond Framework. This holistic framework was formed by organising the identified technology adoption factors into four key dimensions: Human, Technology, Business, and Organisation. To conclude, the AAL Adoption Diamond Framework is holistic in term of recognizing key factors for the adoption of AAL technologies, and novel and unmatched in term of structuring them into four overarching themes or dimensions, bringing together the individual and the systemic factors evolving around the adoption of AAL technology. This framework is useful for stakeholders (e.g., decision-makers, healthcare providers, and caregivers) to adopt and implement AAL technologies.
Effects of Aquatic versus Land High-Intensity Interval Training on Acute Cardiometabolic and Perceptive Responses in Healthy Young Women
Authors: Kwok Manny M. Y. , Poon Eric T. C. , Ng Shamay S. M. , Lai Matthew C. Y. , So Billy C. L.
Published: December 2022

The effects of aquatic high-intensity interval training (AHIIT) on cardiometabolic and perceptive responses when compared to similar land-based exercise (LHIIT) remain unknown. Here, we aimed to (1) establish a matched intensity between mediums and (2) compare the acute cardiometabolic and perceptive responses to the two interventions in healthy young women. Twenty healthy young women performed a stationary running exercise at a matched exercise intensity. The incremental stages, in terms of percentage of heart rate (HR), maximal oxygen uptake (%VO2max), percentage of oxygen uptake reserve (%VO2R), percentage of heart rate reserve (%HRR), and rate of perceived exertion (RPE), were examined and acute cardiometabolic and perceptive responses were evaluated. The results showed that HR was significantly reduced (AHIIT: W 150 ± 19, R 140 ± 18, LHIIT: W 167 ± 16, R 158 ± 16 p < 0.01) and oxygen pulse (AHIIT: W 12 ± 2, R 10 ± 2, LHIIT: W 11 ± 2, R 9 ± 2 p < 0.05) was significantly increased with AHIIT compared to LHIIT. No significant group differences were observed for the perceptive responses. The comparable results demonstrated by the aquatic and land incremental tests allow precise AHIIT and LHIIT prescriptions. AHIIT had distinct differences in HR and oxygen pulse, despite having no distinct difference from LHIIT for some cardiometabolic and affective responses.
The Correlation of Built Environment on Hypertension, and Weight Status amongst Adolescence in Saudi Arabia
Authors: Al-Nuaim Anwar , Safi Ayazullah
Published: December 2022

The prevalence of hypertension is becoming more common in children and adolescents than ever before. Thus, the aim of this study was to evaluate the associations between the built environment on physical activity, sedentary behaviour, waist circumference, and health amongst adolescents in Saudi Arabia. A systolic and diastolic blood pressure, resting heart rate and waist circumference of 380 boys and girls aged between 15–19 years old (male = 199 and females = 181) were measured. The International physical activity Questionnaire Short Form was used to assess the physical activity levels and time spent sitting. The statistical analysis conducted were means and standard deviation, 2-way and 3-way of variance (ANOVA), Bonferroni post hoc tests, Chi-squared distribution and Pearson’s correlations. Among males, 16.75% were classified as hypertensive, 12.69% as pre-hypertensive, and 70.56% as normal whereas, females, 23.20% were classified as hypertensive, 12.15% as pre-hypertensive and 64.64% as normal. There were significant differences (F1,379 = 16.50, p < 0.001) between males and females waist circumference. Pearson’s correlation also revealed significant positive relationships in sedentary time (r = 0.123, p < 0.016), WC (r = 0.104, p < 0.043), and systolic blood pressure (r = 0.110, p < 0.032). The results revealed that systolic and diastolic blood pressure are significantly related to multiple measures of weight status, and sedentary behaviour. The results also highlight that active youth had lower resting heart rate compared to inactive peers. The present findings provide a foundation of knowledge for future research and highlight the major need for research and policy interventions, to address the concerning health habits of Al-Ahsa youth and broader Kingdom of Saudi Arabia.
New Models for Estimating the Sorption of Sulfonamide and Tetracycline Antibiotics in Soils
Authors: Hu Jinsheng , Tang Xiangyu , Qi Minghui , Cheng Jianhua
Published: December 2022

Sulfonamides (SAs) and tetracyclines (TCs) are two classes of widely used antibiotics. There is a lack of easy models for estimating the parameters of antibiotic sorption in soils. In this work, a dataset of affinity coefficients (Kf and Kd) of seven SA/TC antibiotics (i.e., sulfachlorpyridazine, sulfamethazine, sulfadiazine, sulfamethoxazole, oxytetracycline, tetracycline, and chlortetracycline) and associated soil properties was generated. Correlation analysis of these data showed that the affinity coefficients of the SAs were predominantly affected by soil organic matter and cation exchange capacity, while those of the TCs were largely affected by soil organic matter and pH. Pedotransfer functions for estimating Kf and Kd were built by multiple linear regression analysis and were satisfactorily validated. Their performances would be better for soils having higher organic matter content and lower pH. These pedotransfer functions can be used to aid environmental risk assessment, prioritization of antibiotics and identification of vulnerable soils.
Epidemiological Characteristics and Spatio-Temporal Distribution of Hepatitis A in Spain in the Context of the 2016/2017 European Outbreak
Authors: Guerrero-Vadillo María , Peñuelas Marina , Domínguez Ángela , Godoy Pere , Gómez-Barroso Diana , Soldevila Nuria , Izquierdo Conchita , Martínez Ana , Torner Nuria , Avellón Ana , Rius Cristina , Varela Carmen
Published: December 2022

The aim of our study was to describe the results of the epidemiological surveillance of hepatitis A infections in Spain in the context of the 2016/2017 European outbreak, particularly of hepatitis A outbreaks reported in the MSM population, incorporating the results of a spatio-temporal analysis of cases. Hepatitis A cases and outbreaks reported in 2016–2017 to the National Epidemiological Surveillance Network were reviewed: outbreaks in which some of the cases belonged to the MSM group were described, and clusters of hepatitis A cases in men and women were analysed using a space–time scan statistic. Twenty-six outbreaks were identified, with a median size of two cases per outbreak, with most of the outbreak-related cases belonging to the 15–44 years-old group. Nearly 85% occurred in a household setting, and in all outbreaks, the mode of transmission was direct person-to-person contact. Regarding space–time analysis, twenty statistically significant clusters were identified in the male population and eight in the female population; clusters in men presented a higher number of observed cases and affected municipalities, as well as a higher percentage of municipalities classified as large urban areas. The elevated number of cases detected in clusters of men indicates that the number of MSM-related outbreaks may be higher than reported, showing that spatio-temporal analysis is a complementary, useful tool which may improve the detection of outbreaks in settings where epidemiological investigation may be more challenging.
Family Life Cycle, Asset Portfolio, and Commercial Health Insurance Demand in China
Authors: Tian Ling , Dong Haisong
Published: December 2022

Based on the cross-sectional data of the China household finance survey (CHFS) in 2017, this paper aims to empirically examine the effects of the family life cycle, financial status, and asset portfolio on commercial health insurance demand (breadth and depth) by constructing Probit and Tobit models, respectively. Based on all of the samples, it has been found that family life cycle, family financial status, and family asset portfolio have different influences on the breadth and the depth of health insurance. In terms of the family life cycle, there is an “inverted U-shaped” relationship with the breadth and the depth of health insurance, and the effect is obvious. In terms of family financial status, total household consumption has positive and significant effects on the breadth and depth of health insurance. Total household income and total household debt only have a significant positive impact on health insurance breadth. The total household asset portfolio is only positively correlated with health insurance depth. In terms of the family asset portfolio, the share of real estate assets has a crowding out effect on the breadth and the depth of health insurance. The share of savings assets has no significant effect on the breadth and the depth of health insurance but is positively correlated with the former and negatively correlated with the latter. Both the share of vehicle assets and the share of investment assets only have a significant impact on the breadth of health insurance; however, the positive and negative correlation is different. Based on the sub-samples, it has been found that the breadth and the depth of health insurance vary greatly in the regions and household registration characteristics.
Thermodynamic Modeling and Exergy Analysis of A Combined High-Temperature Proton Exchange Membrane Fuel Cell and ORC System for Automotive Applications
Authors: Li Yanju , Yang Mingfei , Ma Zheshu , Zheng Meng , Song Hanlin , Guo Xinjia
Published: December 2022

A combined system consisting of a high-temperature proton exchange membrane fuel cell (HT-PEMFC) and an organic Rankine cycle (ORC) is provided for automotive applications in this paper. The combined system uses HT-PEMFC stack cathode exhaust gas to preheat the inlet gas and the ORC to recover the waste heat from the stack. The model of the combined system was developed and the feasibility of the model was verified. In addition, the evaluation index of the proposed system was derived through an energy and exergy analysis. The numerical simulation results show that the HT-PEMFC stack, cathode heat exchanger, and evaporator contributed the most to the total exergy loss of the system. These components should be optimized as a focus of future research to improve system performance. The lower current density increased the ecological function and the system efficiency, but reduced the system’s net out-power. A higher inlet temperature and higher hydrogen pressures of the stack and the lower oxygen pressure helped improve the system performance. Compared to the HT-PEFC system without an ORC subsystem, the output power of the combined system was increased by 12.95%.
The Modular Architecture of Metallothioneins Facilitates Domain Rearrangements and Contributes to Their Evolvability in Metal-Accumulating Mollusks
Authors: Calatayud Sara , Garcia-Risco Mario , Pedrini-Martha Veronika , Niederwanger Michael , Dallinger Reinhard , Palacios Òscar , Capdevila Mercè , Albalat Ricard
Published: December 2022

Protein domains are independent structural and functional modules that can rearrange to create new proteins. While the evolution of multidomain proteins through the shuffling of different preexisting domains has been well documented, the evolution of domain repeat proteins and the origin of new domains are less understood. Metallothioneins (MTs) provide a good case study considering that they consist of metal-binding domain repeats, some of them with a likely de novo origin. In mollusks, for instance, most MTs are bidomain proteins that arose by lineage-specific rearrangements between six putative domains: α, β1, β2, β3, γ and δ. Some domains have been characterized in bivalves and gastropods, but nothing is known about the MTs and their domains of other Mollusca classes. To fill this gap, we investigated the metal-binding features of NpoMT1 of Nautilus pompilius (Cephalopoda class) and FcaMT1 of Falcidens caudatus (Caudofoveata class). Interestingly, whereas NpoMT1 consists of α and β1 domains and has a prototypical Cd2+ preference, FcaMT1 has a singular preference for Zn2+ ions and a distinct domain composition, including a new Caudofoveata-specific δ domain. Overall, our results suggest that the modular architecture of MTs has contributed to MT evolution during mollusk diversification, and exemplify how modularity increases MT evolvability.
FLIM of NAD(P)H in Lymphatic Nodes Resolves T-Cell Immune Response to the Tumor
Authors: Izosimova Anna V. , Shirmanova Marina V. , Shcheslavskiy Vladislav I. , Sachkova Daria A. , Mozherov Artem M. , Sharonov George V. , Zagaynova Elena V. , Yuzhakova Diana V.
Published: December 2022

Assessment of T-cell response to the tumor is important for diagnosis of the disease and monitoring of therapeutic efficacy. For this, new non-destructive label-free methods are required. Fluorescence lifetime imaging (FLIM) of metabolic coenzymes is a promising innovative technology for the assessment of the functional status of cells. The purpose of this work was to test whether FLIM can resolve metabolic alterations that accompany T-cell reactivation to the tumors. The study was carried out on C57Bl/6 FoxP3-EGFP mice bearing B16F0 melanoma. Autofluorescence of the immune cells in fresh lymphatic nodes (LNs) was investigated. It was found that fluorescence lifetime parameters of nicotinamide adenine dinucleotide (phosphate) NAD(P)H are sensitive to tumor development. Effector T-cells in the LNs displayed higher contribution of free NADH, the form associated with glycolysis, in all tumors and the presence of protein-bound NADPH, associated with biosynthetic processes, in the tumors of large size. Flow cytometry showed that the changes in the NADH fraction of the effector T-cells correlated with their activation, while changes in NADPH correlated with cell proliferation. In conclusion, FLIM of NAD(P)H in fresh lymphoid tissue is a powerful tool for assessing the immune response to tumor development.
N-Functionalization of 5-Aminotetrazoles: Balancing Energetic Performance and Molecular Stability by Introducing ADNP
Authors: Xiong Jin , Chang Jinjie , Cai Jinxiong , Yin Ping , Pang Siping
Published: December 2022

5-aminotetrazole is one of the most marked high-nitrogen tetrazole compounds. However, the structural modification of 5-aminotetrazole with nitro groups often leads to dramatically decreased molecular stability, while the N-bridging functionalization does not efficiently improve the density and performance. In this paper, we report on a straightforward approach for improving the density of 5-aminotetrazole by introducing 4-amino-3,5-dinitropyrazole. The following experimental and calculated properties show that nitropyrazole functionalization competes well with energetic performance and mechanic sensitivity. All compounds were thoroughly characterized using IR and NMR spectroscopy, elemental analysis, and differential scanning calorimetry (DSC). Two energetic compounds (DMPT-1 and DMPT-2) were further confirmed by implementing single-crystal X-ray diffraction studies. Compound DMPT-1 featured a high crystal density of 1.806 g cm−3, excellent detonation velocity (vD = 8610 m s−1), detonation pressure (P = 30.2 GPa), and impact sensitivity of 30 J.
Application of Long-Read Nanopore Sequencing to the Search for Mutations in Hypertrophic Cardiomyopathy
Authors: Salakhov Ramil R. , Golubenko Maria V. , Valiakhmetov Nail R. , Pavlyukova Elena N. , Zarubin Aleksei A. , Babushkina Nadezhda P. , Kucher Aksana N. , Sleptcov Aleksei A. , Nazarenko Maria S.
Published: December 2022

Increasing evidence suggests that both coding and non-coding regions of sarcomeric protein genes can contribute to hypertrophic cardiomyopathy (HCM). Here, we introduce an experimental workflow (tested on four patients) for complete sequencing of the most common HCM genes (MYBPC3, MYH7, TPM1, TNNT2, and TNNI3) via long-range PCR, Oxford Nanopore Technology (ONT) sequencing, and bioinformatic analysis. We applied Illumina and Sanger sequencing to validate the results, FastQC, Qualimap, and MultiQC for quality evaluations, MiniMap2 to align data, Clair3 to call and phase variants, and Annovar’s tools and CADD to assess pathogenicity of variants. We could not amplify the region encompassing exons 6–12 of MYBPC3. A higher sequencing error rate was observed with ONT (6.86–6.92%) than with Illumina technology (1.14–1.35%), mostly for small indels. Pathogenic variant p.Gln1233Ter and benign polymorphism p.Arg326Gln in MYBPC3 in a heterozygous state were found in one patient. We demonstrated the ability of ONT to phase single-nucleotide variants, enabling direct haplotype determination for genes TNNT2 and TPM1. These findings highlight the importance of long-range PCR efficiency, as well as lower accuracy of variant calling by ONT than by Illumina technology; these differences should be clarified prior to clinical application of the ONT method.
Diosgenin Exerts Analgesic Effects by Antagonizing the Selective Inhibition of Transient Receptor Potential Vanilloid 1 in a Mouse Model of Neuropathic Pain
Authors: Rahman Md. Mahbubur , Jo Hyun Jung , Park Chul-Kyu , Kim Yong Ho
Published: December 2022

Diosgenin is a botanical steroidal saponin with immunomodulatory, anti-inflammatory, anti-oxidative, anti-thrombotic, anti-apoptotic, anti-depressant, and anti-nociceptive effects. However, the effects of diosgenin on anti-nociception are unclear. Transient receptor potential vanilloid 1 (TRPV1) plays an important role in nociception. Therefore, we investigated whether TRPV1 antagonism mediates the anti-nociceptive effects of diosgenin. In vivo mouse experiments were performed to examine nociception-related behavior, while in vitro experiments were performed to examine calcium currents in dorsal root ganglion (DRG) and Chinese hamster ovary (CHO) cells. The duration of capsaicin-induced licking (pain behavior) was significantly reduced following oral and intraplantar administration of diosgenin, approaching levels observed in mice treated with the TRPV1 antagonist N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl) tetrahydropyrazine-1(2H)-carbox-amide. Additionally, oral administration of diosgenin blocked capsaicin-induced thermal hyperalgesia. Further, diosgenin reduced capsaicin-induced Ca2+ currents in a dose-dependent manner in both DRG and CHO cells. Oral administration of diosgenin also improved thermal and mechanical hyperalgesia in the sciatic nerve constriction injury-induced chronic pain model by reducing the expression of TRPV1 and inflammatory cytokines in DRG cells. Collectively, our results suggest that diosgenin exerts analgesic effects via antagonism of TRPV1 and suppression of inflammation in the DRG in a mouse model of neuropathic pain.
Differential Effects of Somatostatin, Octreotide, and Lanreotide on Neuroendocrine Differentiation and Proliferation in Established and Primary NET Cell Lines: Possible Crosstalk with TGF-β Signaling
Authors: Ungefroren Hendrik , Künstner Axel , Busch Hauke , Franzenburg Sören , Luley Kim , Viol Fabrice , Schrader Jörg , Konukiewitz Björn , Wellner Ulrich F. , Meyhöfer Sebastian M. , Keck Tobias , Marquardt Jens-Uwe , Lehnert Hendrik
Published: December 2022

GEP-NETs are heterogeneous tumors originating from the pancreas (panNET) or the intestinal tract. Only a few patients with NETs are amenable to curative tumor resection, and for most patients, only palliative treatments to successfully control the disease or manage symptoms remain, such as with synthetic somatostatin (SST) analogs (SSAs), such as octreotide (OCT) or lanreotide (LAN). However, even cells expressing low levels of SST receptors (SSTRs) may exhibit significant responses to OCT, which suggests the possibility that SSAs signal through alternative mechanisms, e.g., transforming growth factor (TGF)-β. This signaling mode has been demonstrated in the established panNET line BON but not yet in other permanent (i.e., QGP) or primary (i.e., NT-3) panNET-derived cells. Here, we performed qPCR, immunoblot analyses, and cell counting assays to assess the effects of SST, OCT, LAN, and TGF-β1 on neuroendocrine marker expression and cell proliferation in NT-3, QGP, and BON cells. SST and SSAs were found to regulate a set of neuroendocrine genes in all three cell lines, with the effects of SST, mainly LAN, often differing from those of OCT. However, unlike NT-3 cells, BON cells failed to respond to OCT with growth arrest but paradoxically exhibited a growth-stimulatory effect after treatment with LAN. As previously shown for BON, NT-3 cells responded to TGF-β1 treatment with induction of expression of SST and SSTR2/5. Of note, the ability of NT-3 cells to respond to TGF-β1 with upregulation of the established TGF-β target gene SERPINE1 depended on cellular adherence to a collagen-coated matrix. Moreover, when applied to NT-3 cells for an extended period, i.e., 14 days, TGF-β1 induced growth suppression as shown earlier for BON cells. Finally, next-generation sequencing-based identification of microRNAs (miRNAs) in BON and NT-3 revealed that SST and OCT impact positively or negatively on the regulation of specific miRNAs. Our results suggest that primary panNET cells, such as NT-3, respond similarly as BON cells to SST, SSA, and TGF-β treatment and thus provide circumstantial evidence that crosstalk of SST and TGF-β signaling is not confined to BON cells but is a general feature of panNETs.
µ-Opioid Receptors Expressed by Intrinsically Photosensitive Retinal Ganglion Cells Contribute to Morphine-Induced Behavioral Sensitization
Authors: Bergum Nikolas , Berezin Casey-Tyler , King Connie M. , Vigh Jozsef
Published: December 2022

Opioid drugs are the most effective tools for treating moderate to severe pain. Despite their analgesic efficacy, long-term opioid use can lead to drug tolerance, addiction, and sleep/wake disturbances. While the link between opioids and sleep/wake problems is well-documented, the mechanism underlying opioid-related sleep/wake problems remains largely unresolved. Importantly, intrinsically photosensitive retinal ganglion cells (ipRGCs), the cells that transmit environmental light/dark information to the brain’s sleep/circadian centers to regulate sleep/wake behavior, express μ-opioid receptors (MORs). In this study, we explored the potential contribution of ipRGCs to opioid-related sleep/circadian disruptions. Using implanted telemetry transmitters, we measured changes in horizontal locomotor activity and body temperature in mice over the course of a chronic morphine paradigm. Mice lacking MORs expressed by ipRGCs (McKO) exhibited reduced morphine-induced behavioral activation/sensitization compared with control littermates with normal patterns of MOR expression. Contrastingly, mice lacking MORs globally (MKO) did not acquire morphine-induced locomotor activation/sensitization. Control mice also showed morphine-induced hypothermia in both the light and dark phases, while McKO littermates only exhibited morphine-induced hypothermia in the dark. Interestingly, only control animals appeared to acquire tolerance to morphine’s hypothermic effect. Morphine, however, did not acutely decrease the body temperature of MKO mice. These findings support the idea that MORs expressed by ipRGCs could contribute to opioid-related sleep/wake problems and thermoregulatory changes.
Aphicidal Activity and Phytotoxicity of Citrus sinensis Essential-Oil-Based Nano-Insecticide
Authors: Laudani Francesca , Campolo Orlando , Caridi Roberta , Latella Ilaria , Modafferi Antonino , Palmeri Vincenzo , Sorgonà Agostino , Zoccali Paolo , Giunti Giulia
Published: December 2022

Due to its high polyphagy, Aphis gossypii is considered a key pest of many crops, and it can feed on hundreds of plant species belonging to the families Cucurbitaceae, Malvaceae, Solanaceae, Rutaceae, and Asteraceae. The control of this pest mainly relies on synthetic insecticides whose adverse effects on the environment and human health are encouraging researchers to explore innovative, alternative solutions. In this scenario, essential oils (EOs) could play a key role in the development of ecofriendly pesticides. In this study, the development of a citrus peel EO-based nano-formulation and its biological activity against A. gossypii both in the laboratory and field were described and evaluated. The phytotoxicity towards citrus plants was also assessed. The developed nano-insecticide highlighted good aphicidal activity both in the laboratory and field trials, even at moderate EO concentrations. However, the highest tested concentrations (4 and 6% of active ingredient) revealed phytotoxic effects on the photosynthetic apparatus; the side effects need to be carefully accounted for to successfully apply this control tool in field conditions.
Copper Exposure Affects Anti-Predatory Behaviour and Acetylcholinesterase Levels in Culex pipiens (Diptera, Culicidae)
Authors: Amer Nermeen R. , Lawler Sharon P. , Zohdy Nawal M. , Younes Aly , ElSayed Wael M. , Wos Guillaume , Abdelrazek Samah , Omer Hind , Connon Richard E.
Published: December 2022

Copper is an essential metal that occurs chronically in the environment and affects the development and physiology of aquatic insects. In excess amounts, it can impair their nervous system and behaviour. We tested the anti-predatory behaviour of Cx. pipiens larvae after seven days exposure with several concentrations of copper up to 500 mg L−1. We measured responses to non- consumptive (predation cues) and consumptive predation (dragonfly larvae) across two generations. We also tested the accumulated effect of copper on AChE enzyme activity. We exposed half of treated and control larvae to predation cues (water with predator odour and crushed conspecifics) and the other half to water without predation cues. We evaluated total distance moved and velocity. Copper reduced the distance moved and velocity, with stronger effects in the second generation. Copper had no significant effect on larvae eaten by dragonflies. Copper inhibited the AChE enzyme across both generations at 500 µg L−1. Copper can affect the nervous system directly by inhibiting AChE activity, and possibly also by impairing the olfaction sensors of the larvae, resulting in larval inability to detect predation cues.
In Silico Modelling to Assess the Electrical and Thermal Disturbance Provoked by a Metal Intracoronary Stent during Epicardial Pulsed Electric Field Ablation
Authors: González-Suárez Ana , Pérez Juan J. , O’Brien Barry , Elahi Adnan
Published: December 2022

Background: Pulsed Electric Field (PEF) ablation has been recently proposed to ablate cardiac ganglionic plexi (GP) aimed to treat atrial fibrillation. The effect of metal intracoronary stents in the vicinity of the ablation electrode has not been yet assessed. Methods: A 2D numerical model was developed accounting for the different tissues involved in PEF ablation with an irrigated ablation device. A coronary artery (with and without a metal intracoronary stent) was considered near the ablation source (0.25 and 1 mm separation). The 1000 V/cm threshold was used to estimate the ‘PEF-zone’. Results: The presence of the coronary artery (with or without stent) distorts the E-field distribution, creating hot spots (higher E-field values) in the front and rear of the artery, and cold spots (lower E-field values) on the sides of the artery. The value of the E-field inside the coronary artery is very low (~200 V/cm), and almost zero with a metal stent. Despite this distortion, the PEF-zone contour is almost identical with and without artery/stent, remaining almost completely confined within the fat layer in any case. The mentioned hot spots of E-field translate into a moderate temperature increase (<48 °C) in the area between the artery and electrode. These thermal side effects are similar for pulse intervals of 10 and 100 μs. Conclusions: The presence of a metal intracoronary stent near the ablation device during PEF ablation simply ‘amplifies’ the E-field distortion already caused by the presence of the vessel. This distortion may involve moderate heating (<48 °C) in the tissue between the artery and ablation electrode without associated thermal damage.
Effect of Scanning Origin Location on Data Accuracy of Abutment Teeth Region in Digital Impression Acquired Using Intraoral Scanner for Removable Partial Denture: A Preliminary In Vitro Study
Authors: Kim Eung-Yeol , Wada Junichiro , Sakamoto Kazuki , Ishioka Yurika , Arai Yuki , Murakami Natsuko , Yamazaki Toshiki , Hayama Hironari , Utsumi Miona , Inukai Shusuke , Wakabayashi Noriyuki
Published: December 2022

The aim of this study was to investigate the effect of scanning origin location on the data accuracy of removable partial denture (RPD) abutment teeth region in digital impressions acquired by an intraoral scanner. A mandibular partially edentulous model including the following target abutment teeth was used: the left second molar (#37); left first premolar (#34); and right second premolar (#45). The following scanning strategies were tested: the strategy starting from #37 to mesial direction (37M); strategies starting from #34 to mesial (34M) and distal directions (34D), and strategies starting from #45 to mesial (45M) and distal directions (45D). The evaluated measures were trueness, precision, and linear accuracy. One-way and two-way ANOVA were performed for the comparison of trueness and linear accuracy, while Kruskal–Wallis test was performed for the precision comparison (α = 0.05). 45M and 45D showed significantly superior trueness of #34 to 37M and 34D. 45M also showed significantly superior trueness of #45 to 34. 45D showed significantly inferior linear accuracy of #34 and superior linear accuracy of #45 compared to other strategies. It was concluded that scanning origin location would have an impact on data accuracy of RPD abutment teeth region in digital impressions acquired by intraoral scanner.
Long-Term Follow-Up of Lower Urinary Tract Outcome in Children with Dysfunctional Voiding
Authors: Peng Chung-Hsin , Chen Sheng-Fu , Kuo Hann-Chorng
Published: December 2022

Objective: To investigate the long-term clinical and urodynamic outcomes of a small cohort of children who received short-term urotherapy for confirmed dysfunctional voiding (DV) and lower urinary tract symptoms (LUTS). Materials and Methods: This study included 26 children with confirmed LUTS and DV via video urodynamic study (VUDS) and received standard urological therapy, pelvic floor muscle training, or surgical intervention in childhood. Their current lower urinary tract conditions were assessed by chart review and direct and telephone interviews. Charts of 14 patients who underwent follow-up VUDS were reviewed to investigate their bladder and voiding dysfunction or follow-up on previous treatment results. The satisfaction of lower urinary tract status was assessed using the global response assessment (GRA) scale. Results: At initial enrolment, the mean age was 9.54 ± 3.88 years, and urological treatment was performed during the first 1–5 years thereafter. Most patients were not regularly followed in the urology clinic. Among the 14 children available for follow-up, a GRA score of 3 was reported by 10 (71.4%) after a mean follow-up period of 10.3 ± 6.74 (range, 2–20) years, indicating satisfactory bladder and voiding conditions. Four children with less favorable outcomes (GRA score of <3) had significantly more post-void residual urine volume at baseline, and 75% of these patients had central nervous system diseases. Daytime incontinence and enuresis rates were significantly decreased at follow-up compared with the baseline. Significantly increased bladder capacity and sensation and significantly decreased voiding detrusor pressure were found on follow-up VUDS. Conclusions: Children with DV who received standard urotherapy upon diagnosis exhibited improved LUTS at a 10-year follow-up. Of the 14 children available for follow-up, 10 (71.4%) reported satisfactory bladder and voiding status without further medication or urotherapy, with significantly decreased voiding detrusor pressure.
Changes in Sleep Problems in Patients Who Underwent Surgical Treatment for Degenerative Spinal Disease with a Concurrent Sleep Disorder: A Nationwide Cohort Study in 3183 Patients during a Two-Year Perioperative Period
Authors: Kim Jihye , Kim Jang Hyun , Kim Tae-Hwan
Published: December 2022

Sleep disturbance is prevalent in patients with degenerative spinal disease, and recent studies have reported that surgical treatment is more effective for improving sleep quality than conservative treatment. We aimed to investigate the perioperative changes of sleep problems in patients who underwent surgical treatment for degenerative spinal disease with a concurrent sleep disorder, and presented them according to various clinical profiles possibly associated with sleep disturbance. In addition, we identified factors associated with poor sleep improvement after surgery. This study used data from the Korea Health Insurance Review and Assessment Service database from 2016 to 2018. We included 3183 patients aged ≥19 years who underwent surgery for degenerative spinal disease and had a concurrent sleep disorder. Perioperative changes in the two target outcomes, including the use of sleep medication and hospital visits owing to sleep disorders, were precisely investigated according to factors known to be associated with sleep disturbance, including demographics, comorbidities, and spinal regions. Logistic regression analysis was performed to identify factors associated with poor improvement in terms of sleep medication after surgery. All estimates were validated using bootstrap sampling. During the 1-year preoperative period, the use of sleep medications and hospital visits owing to sleep disorder increased continuously. However, they abruptly decreased shortly after surgical treatment, and throughout the 1-year postoperative period, they remained lower than those in the late preoperative period. At the 1-year follow-up, 75.6% (2407 of 3183) of our cohort showed improvement in sleep medication after surgery. Multivariable analysis identified only two variables as significant factors associated with non-improvement in sleep medication after surgery: depressive disorder (odds ratio (OR) = 1.25 [1.06–1.48]; p = 0.008), and migraine (OR = 1.42 [1.04–1.94]; p = 0.028). We could not investigate the actual sleep quality and resultant quality of life; however, our results justify the necessity for further high-quality studies that include such information and would arouse clinicians’ attention to the importance of sleep disturbance in patients with degenerative spinal disease.