bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA SNHG6 binds to EEF1D through COPS5/P27 pathway to affect the cycle and proliferation of hepatocellular carcinoma
Authors: Ma Weijie , Liu Bin , Li Xiaomian , Guo Yonghua , Gao Meng , Hao Xingyuan , Liu Fusheng , Zhang Yang-Wen-Qing , Zhou Jitong , Yuan Yufeng
Published: August 2023

Our previous work had suggested that LncRNA SNHG6 interacted with COPS5 and their expression was positively correlated in hepatocellular carcinoma(HCC). In this study we found that SNHG6 and COPS5 was upregulated in HCC patients, and patients with high expression of SNHG6 and COPS5 had worse overall survival(OS). After RNA pulldown experiments and mass spectrometry analysis of SNHG6, and CO-IP experiments and mass spectrometry analysis of COPS5, we finally determined that EEF1D interacted both SNHG6 and COPS5. EEF1D, which had high expression in HCC tissues and cell lines, was related to poor prognosis. Meanwhile, SNHG6, EEF1D and COPS5 could affect the cell cycle and promote proliferation of HCC. Subcutaneous tumors grown from SNHG6-knockdown cells were inhibited compared to control cells. Knocking down SNHG6 or EEF1D leads to faster degradation of COPS5 protein, and activate COPS5/P27 pathway. The first domain leucine zipper of EEF1D was the binding site to COPS5. Eventually, SNHG6 binds to EEF1D and stabilize COPS5 and activate the P27 pathway, affecting the cell cycle to accelerate cell proliferation. SNHG6 may serve as a new target for the diagnosis and treatment of HCC.
Sea Level Variability and Predictions Using Artificial Neural Networks and Machine Learning Techniques in the Gulf of Guinea
Authors: Ayinde Akeem Shola , YU Huaming , WU Kejian
Published: August 2023

The rising sea level due to climate change poses a critical threat, particularly affecting vulnerable low-lying coastal areas such as the Gulf of Guinea (GoG). This impact necessitates precise sea level prediction models to guide planning and mitigation efforts for safeguarding coastal communities and ecosystems. This study presents a comprehensive analysis of mean sea level anomaly (MSLA) trends in the GoG between 1993 and 2020. The assessment covers three distinct periods (1993–2002, 2003–2012, and 2013–2020) and investigates connections between interannual sea level variability and large-scale oceanic and atmospheric forcings. Additionally, the performance of artificial neural networks (LSTM and MLPR) and machine learning techniques (MLR, GBM, and RFR) is evaluated to optimize sea level predictions. The findings reveal a consistent rise in MSLA linear trends across the basin, particularly pronounced in the north, with a total linear trend of 88 mm/year over the entire period. The highest decadal trend (38.7 mm/year) emerged during 2013–2020, and the most substantial percentage increment (100%) occurred in 2003–2012. Spatial variation in decadal sea-level trends was influenced by subbasin physical forcings. Strong interannual signals in the spatial sea level distribution were identified, linked to large-scale oceanic and atmospheric phenomena. Seasonal variations in sea level trends are attributed to seasonal changes in the forcing factors. Model evaluation indicates RFR and GBR as accurate methods, reproducing interannual sea level patterns with 97% and 96% accuracy, respectively. These findings contribute essential insights for effective coastal management and climate adaptation strategies in the GoG.
Longitudinal association of oral function and dementia in Japanese elderly people
Authors: Iwai Komei , Azuma Tetsuji , Yonenaga Takatoshi , Sasai Yasuyuki , Nomura Taketsugu , Sugiura Iwane , Inagawa Yujo , Matsumoto Yusuke , Nakashima Seiji , Abe Yoshikazu , Tomofuji Takaaki
Published: August 2023

The relationship between oral function and dementia was examined in 7384 elderly people (age ≥ 75 years) who visited a dental clinic in Gifu, Japan. Participants without dementia in a baseline survey in April 2018 were followed until March 2021. As oral functions, chewing function, tongue and lip function, and swallowing function were assessed by self-administered questionnaire, by oral diadochokinesis test, and by repetitive saliva swallowing test, respectively. The presence of systemic diseases was based on data obtained from the National Database of Health Insurance of Japan (NDB). At follow-up, 415 (6%) participants were diagnosed with dementia. Multivariate logistic regression analyses showed the presence of dementia at follow-up was associated with female (odds ratio [OR], 1.386; 95% confidence interval [CI], 1.117–1.719), elderly (OR, 1.078; CI, 1.056–1.101), regular dental checkups (absence; OR, 1.452; CI, 1.180–1.788), brushing frequency ≥ twice/day (absence; OR, 1.510; CI, 1.194–1.911), decayed teeth (presence; OR, 1.328; CI, 1.071–1.648), swallowing function (poor; OR, 1.484; CI, 1.135–1.939) at baseline. It was found that poor swallowing function was associated with the future onset of dementia.
Inequality in exposure and knowledge drives vulnerability to rat-associated leptospirosis among Chicago communities
Authors: Dyer Alexandre , Byers Kaylee A. , Buckley Jacqueline Y. , German Danielle , Murray Maureen H.
Published: August 2023

To predict and prevent public health risks from urban rats, studies often examine zoonotic pathogen prevalence in rats in different urban environments. However, human exposure to rats and their awareness of the associated risks are poorly understood. In this study, we aimed to identify factors associated with two aspects of vulnerability to leptospirosis as a model rat-associated disease: 1) exposure to rat urine in the home and 2) lack of awareness that rats carry leptospirosis. To collect data on residents’ experiences and knowledge about rats, we mailed a survey to randomly-selected households along an income gradient in Chicago. Of 432 complete cases, 36% had observed rat urine in the home and 73% were unaware that rats carry leptospirosis. Using logistic regression, we found that non-white respondents had over three times higher odds of observing rat urine in the home than white respondents. Dog owners and respondents who sought out information about rats, regardless of source, were more likely to be aware that rats carry leptospirosis. When we examined both aspects of vulnerability simultaneously using multinomial regression, we found that residents most vulnerable to leptospirosis (who had been exposed to urine and were not aware that rats carry leptospirosis) were significantly less likely to be white and less likely to be dog owners. Our results suggest that more public education is needed about rat-associated diseases spread through feces and urine and that exposure to rats should be considered another environmental health burden that is disproportionately persistent in underserved communities of color.
Is the development of personality beliefs related to childhood traumas and emotional intelligence levels?: A prospective cross-sectional study
Authors: MADEN Ozgur
Published: August 2023

Background
In this study, it was aimed to determine whether there is a relationship between childhood traumas and emotional intelligence levels and personality beliefs.
Methods
University students who applied for a health board examination, did not have any psychiatric disease history, had childhood trauma (CT (+), 45.0%, n = 174) and had no childhood trauma (CT (-), 55.0%, n = 213) were included in the study. students participated. Sociodemographic data form and Childhood Trauma Scale, Bar-On Emotional Intelligence Scale and Personality Beliefs Scale were given to the participants. Statistical analysis was performed using the SPSS (ver.22.0, Chicago, II, USA) program.
Results
Of the students, 91.0% (n = 352) were male and 46.3% (n = 179) were in the 20–21 age group. Most of them were studying at the faculty of engineering. In those with CT (+), avoidant-personality beliefs, dependent-personality beliefs, passive-aggressive-personality beliefs, antisocial-personality beliefs, histrionic-personality beliefs, schizoid-personality beliefs, paranoid-personality beliefs and borderline-personality beliefs levels and intrapersonal skills, interpersonal skills, adaptability, stress management and general mood emotional intelligence levels were statistically significant compared to those with CT (-) degree was higher. A moderate, positive, statistically significant relationship was found between childhood trauma levels and personality beliefs and emotional intelligence levels, excluding obsessive-compulsive personality beliefs. Furthermore, there was no statistically significant relationship between obsessive-compulsive-personality beliefs and emotional intelligence levels in those with childhood traumas.
Conclusion
Childhood traumas, which can be effective in personality development, may contribute to the development of different components of emotional intelligence and different personality beliefs. Different dimensions of emotional intelligence can also be effective in the emergence of personality beliefs. We would like to emphasize that childhood traumas and emotional intelligence levels are not related to the emergence of obsessive-compulsive beliefs.
Investigating the Potential of 6-Substituted 3-Formyl Chromone Derivatives as Anti-Diabetic Agents Using DFT, Molecular Docking and Molecular Dynamics Methods
Authors: Saif Minhaz Zabin , Esha Nusrat Jahan Ikbal , Quayum Syeda Tasnim , Rahman Shofiur , Al-Gawati Mahmoud , Alsowygh Ghadah , Albrithen Hamad , Alodhayb Abdullah , Poirier Raymond A. , Uddin Kabir M.
Published: August 2023

The focus of this research is to investigate the potential of 6-substituted 3-formyl chromone derivatives (1-16) for various biological activities such as antifungal, antiviral, antibacterial, antiallergenic etc. The research examined the formyl group at the chromone’s C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO-LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of -8.5 kcal mol⁻¹. This result outperformed the affinity of the reference standard dapagliflozin (-7.9 kcal mol⁻¹) as well as two other compounds that target human IDE, namely vitexin (-8.3 kcal mol⁻¹) and myricetin (-8.4 kcal mol⁻¹). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein-ligand complex at the active site.
Augmenting MEK inhibitor Efficacy in BRAF Wild-Type Melanoma: Synergistic Effects of Disulfiram Combination Therapy
Authors: Meraz-Torres Francisco , Niessner Heike , Plöger Sarah , Riel Simon , Schörg Barbara , Casadei Nicolas , Kneilling Manfred , Schaller Martin , Flatz Lukas , Macek Boris , Eigentler Thomas , Rieß Olaf , Garbe Claus , Amaral Teresa , Sinnberg Tobias
Published: August 2023

Background
MEK inhibitors (MEKi) were shown to be clinically insufficiently effective in patients suffering from BRAF wild-type (BRAF WT) melanoma, even if the MAPK pathway was constitutively activated due to mutations in NRAS or NF-1. Thus, novel combinations are needed to increase the efficacy and duration of response to MEKi in BRAF WT melanoma. Disulfiram and its metabolite diethyldithiocarbamate are known to have antitumor effects related to cellular stress, and induction of endoplasmic reticulum (ER) stress was found to synergize with MEK inhibitors in NRAS-mutated melanoma cells. Therefore, we investigated the combination of both therapeutics to test their effects on BRAF-WT melanoma cells and compared them with monotherapy using the MEKi trametinib.
Methods
The effects of combined therapy with disulfiram or its metabolite diethyldithiocarbamate and the MEKi trametinib were evaluated in a series of BRAF-WT melanoma cell lines by measuring cell viability and apoptosis induction. Cytotoxicity was additionally assessed in 3D spheroids, ex vivo melanoma slice cultures, and in vivo xenograft mouse models. The response of melanoma cells to treatment was studied at the RNA and protein levels to decipher the mode of action. Intracellular and intratumoral copper measurements were performed to investigate the role of copper ions in the antitumor cytotoxicity of disulfiram and its combination with the MEKi.
Results
Diethyldithiocarbamate enhanced trametinib-induced cytotoxicity and apoptosis induction in 2D and 3D melanoma culture models. Mechanistically, copper-dependent induction of oxidative stress and ER stress led to Janus kinase (JNK)-mediated apoptosis in melanoma cells. This mechanism was also detectable in patient-derived xenograft melanoma models and resulted in a significantly improved therapeutic effect compared to monotherapy with the MEKi trametinib.
Conclusions
Disulfiram and its metabolite represent an attractive pharmaceutical approach to induce ER stress in melanoma cells that potentiates the antitumor effect of MEK inhibition and may be an interesting candidate for combination therapy of BRAF WT melanoma.
Quantitative differentiation of non-invasive bladder urothelial carcinoma and inverted papilloma based on CT urography
Authors: Jin Pengfei , Yang Liqin , Liu Yitao , Huang Jiehui , Wang Xu
Published: August 2023

Purpose
To investigate the value of CT urography (CTU) indicators in the quantitative differential diagnosis of bladder urothelial carcinoma (BUC) and inverted papilloma of the bladder (IPB).
Material and methods
Retrospective analysis of clinical and imaging data of 103 patients who underwent CTU prior to transurethral resection of the bladder tumor or radical cystectomy from January 2019 to December 2022. The imaging data included 6 qualitative indicators and 7 quantitative measures. The recorded clinical information and imaging features were subjected to univariate and multivariate logistic regression analysis to find independent risk factors for BUC, and a combined multi-indicator prediction model was constructed, and the prediction model was visualized using nomogram. ROC curve analysis was used to calculate and compare the predictive efficacy of independent risk factors and nomogram.
Results
Junction smoothness, maximum longitudinal diameter, tumor-wall interface and arterial reinforcement rate were independent risk factors for distinguishing BUC from IPB. The AUC of the combined model was 0.934 (sensitivity = 0.808, specificity = 0.920, accuracy = 0.835), and its diagnostic efficiency was higher than that of junction smoothness (AUC = 0.667, sensitivity = 0.654, specificity = 0.680, accuracy = 0.660), maximum longitudinal diameter (AUC = 0.757, sensitivity = 0.833, specificity = 0.604, accuracy = 0.786), tumor-wall interface (AUC = 0.888, sensitivity = 0.755, specificity = 0.808, accuracy = 0.816) and Arterial reinforcement rate (AUC = 0.786, sensitivity = 0.936, specificity = 0.640, accuracy = 0.864).
Conclusion
Above qualitative and quantitative indicators based on CTU and the combination of them may be helpful to the differential diagnosis of BUC and IPB, thus better assisting in clinical decision-making.
Comparative Studies on the Seismic Performances of Precast Segmental Columns with Different Concrete, Reinforcement and Tendon Materials
Authors: Li Canjun , Bi Kaiming , Hao Hong , Li Chao
Published: August 2023

In recent years, precast segmental columns cast with Portland cement concrete (OPC) and reinforced with steel rebars have gained popularity in engineering practices owing to its obvious advantages. However, the use of OPC in the construction associates to significant emission of carbon dioxide. Moreover, the corrosion of steel reinforcements and tendon are unavoidable during the lifetime of the structure, which will significantly lower the structural strength and durability. To overcome these issues, very recently, we have proposed using green and sustainable construction materials, i.e., the geopolymer concrete (GPC), together with basalt fibre reinforced polymer (BFRP) reinforcements and tendons, which possess the characteristics of less CO2 emission and excellent corrosion resistant capability, to construct precast segmental columns (i.e., to construct GPC-BFRP segmental columns) for seismic resistant applications. Experimental studies on the proposed GPC-BFRP and the conventional OPC-steel segmental columns were then performed to examine the performances of the proposed design. However, the comparisons of the experimental results were not strictly fair since the key parameters of the two types of columns, e.g., concrete strength and posttension force, in the experiments could not exactly be the same even though they were designed to be the same. This paper therefore extends the recent experimental study and performs numerical simulations. In particular, the experimentally tested columns were used to validate the three-dimensional (3D) finite element models (FEMs) of the two segmental columns with different materials (i.e., OPC-steel and GPC-BFRP). The validated numerical models are then used to examine the seismic performances of these two types of columns under the same design parameters. Numerical results show that under small earthquakes, the two types of columns present almost identical structural responses. Under moderate to severe earthquakes, the two columns also have comparable performances, but GPC-BFRP segmental column presents slightly larger displacement responses and failed slightly earlier because of the smaller BFRP elastic modulus. The results in this study demonstrate the potentials of constructing sustainable and durable GPC-BFRP segmental columns in seismic regions.
Comparative study of the effect of different treatments on infestation development by the red palm weevil Rhynchophorus ferrugineus (Olivier) in Tunisia
Authors: Ouali Othmen , Slimane-Kharrat Saida , Rahmouni Mohamed , Boughanmi Néziha Ghanem
Published: August 2023

Since its entry into Tunisia in 2010, the red palm weevil has dispersed to many parts of the country and killed thousands of canary palms. The purpose of this study is to test several treatment models of RPW control strategies in order to deduce which strategy is the most effective, efficient, ecological and least expensive. These experiments lasted one year and according to the obtained results, the foliar treatments can be reduced from 12 times to 8 times only without having any difference in the evolution of the infestation of this pest. It can have less environmental impact and can make more money. Endotherapy demonstrate a relevant efficacy in the treatment of palm trees, except that specialists should do it in accordance with the rules of the art. Confidor 200 SL prove to be efficacious because the treated palms have not evolved only from 3 months of treatment, so the latter is effective for a duration of only 3 months, Furthermore, the Pro Act 50 CE has at least 7 months of palm protection. On the other hand, foliar treatment in combination with endotherapy did not significantly change the results compared to endotherapy alone. Using pheromone traps with foliar treatments and endotherapies with confidor 200 SL did not show much of a difference from endotherapy alone. In the case of the Pro Act 50 EC, there is no major difference either. Using traps, foliar treatments should be performed to protect the palms from new infestations by females that have won the palms without the traps. This triple treatment in the long term proves effective. Finally, for all stage 4 palms (umbrella) no treatment is curative.
Investigation of the role of rs4238001 genetic polymorphism of SR-B1 gene on serum level of lipids in Iraqi patients with myocardial infarction treated with rosuvastatin
Authors: Abdulfattah shaimaa , Alagely Huda , Samawi Farah
Published: August 2023

The scavenger receptor type B (SR-BI) is a receptor that binds both native and altered lipoproteins. It was revealed to facilitate the utilization of high-density lipoprotein HDL and significantly affect the reverse transport of cholesterol. The present work aims to explore the risk of rs4238001, a nonsynonymous genetic variant in patients of ischemic heart disease (IHD), diagnosis with myocardial infarction, and how this variant could perhaps impact the response of rosuvastatin drug. The genotyping of the rs4238001 genetic polymorphism of the SR-B1 gene was performed in 300 participants, including 150 MI patients treated with 20mg/day/4 weeks of rosuvastatin and 150 healthy using Taq man probes (FAM probe for common C allele and VIC probe for mutant T allele) by Real time-PCR technique. The concentrations of the lipid profile were evaluated. The significance of the anthropometric data was revealed in the ejection fraction and smoking status (p < 0.05) between groups. The lipid profile shows either significant differences between control and MI patient (pre-treatment) or between pre-and post-treatment of MI patients (p < 0.05), but not HDL-c (p > 0.05). The minor allele frequency MAF% of the T allele and TT genotype were more frequent in MI patients than in controls (P = 0.173; OR = 3.62; 95%CI = 0.74–17.64). CC genotype was found to be associated with response to rosuvastatin therapy with a change of % (29.08 ± 53.2; p = 0.021). In the Iraqi population, the rs4238001 polymorphism of the SR-B1 gene is associated with variations in serum lipids, and the CC genotype of the SNP is related to higher HDL-C in the lipid-lowering rosuvastatin response.
Remote Sensing Image Change Detection based on Cross Mixing Attention Network
Authors: WU Xiaosuo , YANG Le , WU Chaoyang , GUO Cunge , WANG Liling , YAN Haowen
Published: August 2023

Change detection is a crucial undertaking in the field of remote sensing. Current change detection methods tend to emphasize modelling difference features, ignoring the alignment error of dual-temporal images and the spatio-temporal relationship between dual-temporal images, which affects the recognition ability of features and makes it difficult to distinguish the real change region. Aiming at the above problems, this paper proposes a remote sensing image change detection method based on cross mixing attention network. The method employs the feature alignment module to obtain dual-temporal correction features to improve the classification effect of the boundary pixels of the target region. The spatio-temporal relationship of the dual-temporal phase images is better exploited by the cross mixing attention module to obtain attention maps at different scales to guide the up-sampling and enhancing the detection performance of target areas at different scales. Our introduced network demonstrates promising performance, as evidenced by extensive experimental results on both the LEVIR-CD dataset and SYSU-CD dataset.
Applicability and Clinical Utility of the German Rivermead Post-Concussion Symptoms Questionnaire in Proxies of Children after Traumatic Brain Injury: An Instrument Validation Study
Authors: Bockhop Fabian , Greving Sven , Zeldovich Marina , Krenz Ugne , Cunitz Katrin , Timmermann Dagmar , Kieslich Matthias , Andelic Nada , Buchheim Anna , Koerte Inga K. , Roediger Maike , Brockmann Knut , Bonfert Michaela V. , Berweck Steffen , Lendt Michael , Staebler Michael , von Steinbuechel Nicole
Published: August 2023

Background. The German Rivermead Post-Concussion Symptoms Questionnaire (RPQ) can be used to assess post-concussion symptoms (PCS) after traumatic brain injury (TBI) in adults, adolescents, and children.
Methods. In this study, we examined the psychometric properties of the German RPQ proxy version (N = 146) for children (8—12 years) after TBI on the item, total and scale score level. Construct validity was analyzed using rank correlations with the proxy-assessed Post-Concussion Symptoms Inventory (PCSI-P), the Patient Health Questionnaire 9 (PHQ-9), and the Generalized Anxiety Disorder Scale 7 (GAD-7). Furthermore, sensitivity testing concerning subjects’ sociodemographic and injury-related characteristics was performed. Differential item functioning (DIF) was conducted to evaluate the comparability of RPQ proxy ratings in children compared to adolescents.
Results. Good internal consistency was shown regarding Cronbach’s α (0.81—0.90) and McDonald’s ω (0.84—0.92). Factorial validity was superior for a three-factor model compared to the original one-factor model. Proxy ratings of the RPQ total and scale scores had strong correlations with the PCSI-P (ϱ = 0.50—0.69), as well as moderate to strong correlations with the PHQ-9 (ϱ = 0.49—0.65) and the GAD-7 (ϱ = 0.44—0.64). DIF analysis revealed no relevant differences between children and adolescent proxy versions.
Conclusions: The German RPQ proxy is a psychometrically reliable and valid instrument to assess PCS in children after TBI. Therefore, RPQ self- and proxy-ratings can be used to assess PCS in childhood as well as along the lifespan of an individual after TBI.
The burden of mental, and substance use disorders in Saudi Arabia: results from the Global Burden of Disease Study 2019
Authors: Ramadan Majed , Aboalola Doaa A. , Alsiary Rawiah , Batwa Yara F.
Published: August 2023

Background Mental and substance use disorders represent a significant global public health challenge causing considerable morbidity and mortality worldwide. This paper assessed the prevalence, incidence, and trends in disability-adjusted life-years (DALYs) rates due to mental and substance use disorders over a 30-year period in Saudi Arabia. Method This is a systematic analysis of the Global Burden of Disease (GBD) 2019 study. Data for the disease burden of mental and substance use disorders were used to Saudi Arabia from 1990 to 2019. Results In 2019, there were 5,032,669 million (95% uncertainty intervals (UI) 3·5–9·9)) adults in Saudi Arabia with mental disorder, and 166,989 thousand with substance use disorder. The largest proportion of prevalence increase from 1990 to 2019 was in eating disorder with 9.8% (95% UI 7.03–12.6). The most significant proportion of prevalence and incidence increase from 1990 to 2019 was in opioid disorders with 69.72% (95% UI 67-72.5), 42.14% (95% UI 32.414–54.75). Gender and age variations were observed in the DALYs due to mental and substance use disorders. From 1990 to 2019 there was + 26.46% increase in the annual change rate of age standardized DALYs due to substance use disorders Conclusion This study highlights the modest increase in the prevalence, incidence, and disability-adjusted life years (DALYs) rates associated with mental disorders in Saudi Arabia over the past three decades. However, there has been a significant rise in the prevalence, incidence, and DALYs rates related to substance use disorders across different gender and age groups. These findings underscore the significance of taking into account age and gender differences in mental and substance use disorders when formulating prevention and treatment initiatives. Further research is warranted to identify the factors contributing to the upward trend in substance use disorders and to devise effective strategies for addressing this critical public health concern.
High Intensity Interval Training (HIIT) Ameliorates the Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats
Authors: Hosseini Najmeh Sadat , Meymandi Manzumeh Shamsi , Sepehri Gholamreza , Dabiri Shahriar , Shirazpour Sara , Zangiabadizadeh Mahla , Bashiri Hamideh
Published: August 2023

Introduction: Tramadol (TRA) is an opioid analgesic widely prescribed for moderate to severe pain; however, its chronic use is associated with kidney damage. Objectives: This study aimed to assess the impacts of high intensity interval training (HIIT) on the male rat's kidney following chronic TRA administration. Methods: In this experimental study, 30 male Wistar rats were assigned to the following groups: CON; animals received normal saline five days a week in the first month and three days a week second month, EXE; animals conducted (HIIT) according to exercise protocol five days a week for two months, TRA; animals received tramadol 50 mg/kg (i.p.) as described for the CON group. TRA-EXE; animals received tramadol and conducted exercise protocol, and EXE-SL; animals received normal saline and conducted exercise protocol. Then serum malondialdehyde (MDA), total antioxidant capacity (TAC), Glutathione peroxidase (GPx), superoxide dismutase (SOD), albumin (ALB), urea, creatinine (CR), and tissue level of TNFα, IL-6, IL-10 with pathological changes in kidney were measured. P < 0.05 was considered significant using Graph-pad Prism v.9. Results: Exercise in TRA-EXE group increased significantly IL-10, IL-6, MDA, urea, and CR levels compared with TRA group (but not compared to CON). As well, SOD, TAC, GPx, and ALB levels were decreased significantly in TRA-EXE compared with TRA group (but not compared to CON). Pathological findings showed increased inflammatory effect of HIIT even in EXE-TRA due to severe hyperemia seen in all exercise groups. Other findings were in line with the above results. Conclusion: The results showed that HIIT was able to reverse most of harmful effects of tramadol on kidney, including tramadol-induced apoptosis, oxidative stress, and kidney function indices. However, HIIT may lead to increased inflammation, unlike chronic use of tramadol which appeared to ameliorate inflammation. Finally, HIIT might be proposed as a therapeutic strategy for chronic users of tramadol.
Disrupted brain mitochondrial morphology after in vivo hydrogen sulfide exposure
Authors: Rumbeiha Wilson K. , Kim Dong-Suk , Min Angela , Nair Maya , Giulivi Cecilia
Published: August 2023

Changes in mitochondrial dynamics are often associated with dietary patterns, medical treatments, xenobiotics, and diseases. Toxic exposures to hydrogen sulfide (H2S) harm mitochondria by inhibiting Complex IV and other mechanisms. However, changes in mitochondrial dynamics, including morphology following acute exposures to H2S, are not yet fully understood. This study followed mitochondrial morphology changes over time after an acute dose (1000 ppm) of H2S by examining electron microscopy images of mouse thalami. Our findings revealed that within the initial 48 h after H2S exposure, the energy-producing capacity of mitochondria was impaired by H2S, supported by the disruption and scarcity of the cristae, which are required to enhance the surface area for ATP production. At the 72-h mark point, a spectrum of morphological cellular changes was observed, and the disordered mitochondrial network, accompanied by the probable disruption of mitophagy, was tied to changes in mitochondrial shape. In summary, this study sheds light on how acute exposure to high levels of H2S triggers alterations in mitochondrial shape and structure as early as 24 h that become more evident at 72 h post-exposure. These findings underscore the impact of H2S on mitochondrial function and overall cellular health.
A Rat Model of Chronic Heart Failure Combined with Intestinal Dysfunction and Alterations in the Microbiome and Metabolomics
Authors: Liu Jiahui , Wei Xiunan , Dai Yonggang , Li Gongyi , Zhang Miaomiao , Liang Junwei , Cheng Yan , Chi Lili
Published: August 2023

Intestinal dysfunction (ID) is considered a critical comorbidity of chronic heart failure (CHF) and can exacerbate the condition. The pathophysiology underlying chronic heart failure combined with intestinal dysfunction (CHF&ID) remains elusive, and animal models are lacking. In this study, we compared four modeling methods, abdominal aortic constriction (AAC), transverse aortic constriction (TAC), TAC combined with cecum ligation (TAC + CL), and AAC combined with cecum ligation (AAC + CL), to establish a rat CHF&ID model. The results demonstrated that TAC + CL elicited a significant elevation in B-type natriuretic peptide (BNP) and trimethylamine N-oxide (TMAO) levels, accompanied by a notable decrease in heart function as assessed by echocardiography. Moreover, this method induced myocardial fibrosis, and cardiomyocyte hypertrophy in rats. Additionally, it was found to induce mechanical barrier damage to the small intestinal, including disorganization of epithelial structure, and increased diamine oxidase (DAO) and lipopolysaccharide (LPS) in rats. Afterward, analysis of the cecal intestinal microbiota using 16S rRNA sequencing technology revealed significant alterations in CHF&ID rats, characterized by an increased abundance of Bacteroides, Ruminococcaceae_UCG-005, NK4A214_group, Family_XIII_AD3011_group, Lachnospiraceae_UCG-010, and Bifidobacterium (p < 0.05), as well as a decreased abundance of Roseburia, Oscillibacter and Tuzzerella (p < 0.05). Detection of serum metabolites by the LC‒MS coupling technique revealed that LysoPC (0:0/18:2(9Z,12Z)), LysoPC (18:3(9Z,12Z,15Z)/0:0), PC (17:1(9Z)/0:0), glycoursodeoxycholic acid were upregulated. Correlation analysis showed that the intestinal microbiota was significantly associated with several lipid metabolites, cardiac remodeling and leaky gut indicators. These results suggest that intestinal microbiota disorders and serum metabolites crosstalk with each other to induce the development of CHF&ID.
Attitudes of Parents of Children with Rare Neurological Disorders Toward Clinical Genetic Testing
Authors: Salayev Kamran , Guliyeva Ulviyya , Guliyeva Sugra , Kaiyrzhanov Rauan , Aslanova Ulviyya , Guliyeva Narmin , Houlden Henry , Munir Kerim
Published: August 2023

Purpose: To study attitudes among parents of probands with rare pediatric-onset neurological and neurodevelopmental disorders on Clinical Genetic Testing (CGT).
Methods: We administered an 8-item direct structured questionnaire comprising statements regarding attitudes on CGT to 101 consenting parents of probands enrolled in the Central Asia and Transcaucasia Disease Diversity Project. The probands comprised pediatric-onset diseases that included cerebral palsy, epilepsy, severe physical, language, and intellectual developmental delays, and autism spectrum symptoms
in children with rare neurological disorders. We studied correlations between parents’ opinions and demographic and clinical characteristics.
Results: The majority of parents (82.1%–91.9%) agreed on statements reflecting the positive effects of CGT (causal explanation, research support, treatment relevance, recurrence prevention, and family planning). The opinions on the negative effects (discrimination, parental concern, and family conflicts) were less uniform. The level of education of parents correlated with statements about causal explanation, research support, and family planning (p < 0.05). Individual concurrent symptoms (severe developmental delay, epilepsy, autism, and microcephaly) correlated with several statements (p < 0.05).
Conclusion: Parents showed positive attitudes toward clinical genetic testing. Parents’ educational level was the most significant factor influencing their opinions. The spectrum and severity of clinical symptoms may shape the attitudes of the parents toward individual aspects of CGT.
Unveiling cell metabolic bioprocess of programmed cell death ligand 1 (PD-L1) expression through nutrients-driven cancer immunomarker progression using SERS technique
Authors: Huang Qing , Muhammad Muhammad , Shao Chang-Sheng , Bashir Mona , Wu Yahui , Zhan Jie , Zhang Leisheng
Published: August 2023

In recent years, the expression and progression of programmed cell death ligand 1 (PD-L1) as an immunomarker in the context of cell metabolic environments have gained significant attention in cancer research. This study aims to explore the dynamic changes of PD-L1 expression and progression within the cell metabolic environment using SERS. The SERS technique offers a sensitive, rapid, and powerful analytical tool that allows for targeted and non-destructive detection of immunomarker with high-sensitivity and specificity. By combining SERS with cell metabolic state-profiling, we investigated the correlation between the metabolic state of cells and PD-L1 immunomarker expression. We assessed the changes in PD-L1 expression under different metabolic states including glucose deprivation, metabolic co-enzyme activity, and altered metabolic cytokines availability. SERS nanotags based on aptamer combined Au/4-ATP/Ag were employed in cells, providing molecular fingerprints of the Raman reporter in cells that reflected the PD-L1 expression levels. Our intricate exploration utilizing PD-L1-aptamer functionalized SERS nanotags underscores the intricate modulation of PD-L1 expression across diverse cellular scenarios. Specifically, we observed that glucose deprivation led to upregulated PD-L1 expression, suggesting a potential link between cellular energy metabolism and immune checkpoint regulation. Additionally, NADPH lead glucose metabolism was found to significantly influence PD-L1 expression dynamics. Our results elucidate concentration-dependent PD-L1 responses to immune signaling molecules, illuminating the sophisticated interplay between glucose metabolism, redox dynamics, and cytokine-mediated regulation in shaping immune checkpoint expression. These findings hold implications for precision-targeted therapeutic interventions in the realm of cancer treatment.
Aberrant structural and functional alterations in patients with insomnia comorbid anxiety: A combined voxel-based morphometry and functional connectivity study
Authors: Xu Minghe , Li Bo , Wang Shuang , Chen Chunlian , Liu Zhe , Ji Yuqing , Liu Kai , Niu Yujun
Published: August 2023

Chronic insomnia disorder (CID) is commonly comorbid with generalized anxiety disorder (GAD), resulting in possible alterations in patient's brain structure and function. However, its imaging manifestation and pathogenesis remains unclear. To investigate the imaging manifestations of patient with CID comorbid GAD, as well as its possible pathogenesis. A total of 57 patients with CID comorbid GAD and 57 healthy controls (HC) were respectively recruited in this study. Voxel-based morphometry (VBM) and functional connectivity (FC) were used to observe the gray matter volume (GMV) and functional alterations. Correlation analysis was used to discover associations between brain alterations and clinical features. The patients presented with decreased GMV in the left cerebellum, right cerebellar peduncle and left insula, increased FC in the left cerebellum-right angular gyrus and the left insula-anterior left cingulate gyrus, and decreased FC in left cerebellum-middle left cingulate gyrus, left cerebellum-left medial superior frontal gyrus, and left insula-left superior postcentral gyrus. There was an association between CID comorbid with GAD and some of these brain alterations. Reduced GMV in left insula and decreased FC in left cerebellum-middle left cingulate gyrus and left cerebellum-left medial superior frontal gyrus may contribute to the comorbidity of CID and GAD.
"Characteristics and Variability of Porcine Reproductive and Respiratory Syndrome Virus Strains: Implications for Virulence and Control - A Scoping Review"
Authors: Martinez Natalia , Machado Gustavo , Golding Megan , Deza-Cruz Inaki , Prada Joaquin M.
Published: August 2023

Background
Porcine reproductive and respiratory syndrome virus (PRRSV) is the responsible agent of one of the most important diseases in the pig industry and is distributed worldwide. There are two main classifications of the virus, PRRSV 1 and PRRSV 2, the first common in Europe and the second in the United States and China. The major challenge in controlling the agent is the significant variation in the strains, which limits the efficiency of vaccines and control measures. We examined peer-reviewed literature to investigate the characteristics and distinctions among various strains and identify the attributes enabling the virus to thrive within pig herds.
We searched the PubMed, Scopus, and Web of Science databases between July and August 2022. We identified 2,847 articles published between 2012 and 2022 and evaluated their eligibility based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Thirty-one articles were finally selected, analysed, and compared to extract and systematise as many factors that account for PRRSV virulence as possible.
Results/conclusions
The selected studies focused on experimental models of PRRSV infection that compared the virulence and pathogenic characteristics of different strains in different age groups. These studies aimed to identify differences in disease development, transmission, and host susceptibility between breeding-age and young pigs. By comparing different parameters, we provided insights into the varying virulence of PRRSV strains. Future research aims to monitor markers that can help understand the complex interactions between the host, pathogen, and environment, improve animal health, and effectively control the consequences of PRRSV infection.
Cathepsin B degrades RbcL during freezing-induced programmed cell death in Arabidopsis
Authors: Yang Gang , Chen Tao , Fan Ting-ting , Lin Xiang-yu , Cui Yu-qiong , Dong Wei-chao , An Li-zhe , Zhang Hua
Published: August 2023

Programmed cell death (PCD) has been well documented in both development and in response to environmental stresses in plants; however, PCD induced by freezing stress and its molecular mechanisms remain poorly understood. In the present study, we characterised freezing-induced PCD and explored its mechanisms in Arabidopsis. PCD induced by freezing stress was similar to that induced by other stresses and senescence in Arabidopsis plants with cold acclimation. Inhibitor treatment assays and immunoblotting indicated that cathepsin B mainly contributed to increased caspase-3-like activity during freezing-induced PCD. Cathepsin B was involved in freezing-induced PCD and degraded the large subunit, RbcL, of Rubisco. Our results demonstrate an essential regulatory mechanism of cathepsin B for Rubisco degradation in freezing-induced PCD, improving our understanding of freezing-induced cell death and nitrogen and carbohydrate remobilisation in plants.
Hardware in Loop Quasi-Static Simulations Dedicated to Evaluation of On Load Tap Changers Distribution Voltage Regulators
Authors: Palma Marcelle Alves Bezerra , Junior José Eduardo da Rocha Alves , Taranto Glauco Nery
Published: August 2023

This paper proposes a new approach for evaluating distribution voltage regulators using quasi-static hardware-in-the-loop (HIL) simulation. Distribution voltage regulators are used to control the voltage using tap change transformers and are equipped with static control algorithms in order to accomplish different configurations of the distribution electric grid with typical load profiles. The growing penetration of renewable energy in electrical distribution systems is a great challenge for this equipment and it becomes paramount that its measurement and control algorithms adapt to this new reality. Hardware in loop testing (HIL) techniques could be used for assessing the performance of the voltage regulator equipment. Most applications of HIL are concerned with accessing the dynamics of electrical system including not only grid modelling, but also the real equipment involved and should be used to test the efficiency of voltage regulation. However, a more simplified approach concerning the HIL tool could be applied to testing distribution voltage regulators in the laboratory prior to installation, evaluating the performance of algorithms and equipment by conducting quasi-static simulations. This paper presents this approach, joining NI LABVIEW laboratory controller software [1] and an open-source program OpenDSS [2]. It is demonstrated the effectiveness of quasi-static HIL platforms for assessing several aspects of static voltage tap regulators before installing them in the electric grid. The major advantage is the smaller computation complexity of a static simulations compared to dynamic simulators, allowing simpler hardware requirements. In this sense, a large number of medium to long term simulations could be easily performed providing a broader view of the behavior of the electric system including voltage regulators.
A rare case of fungal keratitis caused by Tintelnotia destructans
Authors: Barranca Isabel Romero , Caro-Magdaleno Manuel , Mataix-Albert Beatriz , López-Barba José , Cordero-Ramos Jaime , Rodríguez-de-la-Rúa Enrique
Published: August 2023

Background
Fungal keratitis is a rare, potentially sight-threatening fungal infection of the cornea, and a major global cause of visual impairment and blindness. Tintelnotia destructans, a filamentous fungus, is an unusual virulent ocular pathogen. Little is known about this fungi’s association with ophthalmological conditions and there is no standardized treatment protocol in guidelines.
Case presentation:
We report a rare case of T. destructans-associated keratitis in a 45-year-old woman, without history of corneal trauma and a regular contact lenses user, presenting with eye discomfort and redness. Conjunctival hyperemia and a corneal abscess located inferiorly parapupilarly with an epithelial lesion was detected and topical ciprofloxacin eye drops was initiated. In vivo confocal microscopy (IVCM) revealed fungal hyphae growing perpendicularly through the corneal collagen lamellae, suggesting keratomycosis. Culture from corneal scrapings identified the hyphomycete as T. destructans. The diagnosed corneal abscess was treated successfully with natamycin and terbinafine, resulting in symptom regression.
Conclusions
T. destructans is an opportunistic pathogen causing severe keratomycosis with no standardized treatment. Early diagnosis using IVCM and fungal culture, guided by in vitro susceptibility testing, can allow prompt intervention.
RETRACTED: When is the radiology report of a posterior fossa containing cyst/cystic-like CSF collection of clinical or surgical significance?
Authors: Quezada Jeffrey J. , Nelson Marvin D. , McComb J. Gordon
Published: August 2023

The authors have requested that this preprint be removed from Research Square.
Relationship between intraoperative requirement for inhalational anesthetic or opioid and postoperative analgesic consumption: a randomized controlled study
Authors: Lee Jun Ho , Doo A Ram , Oh Jeongmin , Jang Jieun , Ko Seonghoon
Published: August 2023

Background
This study investigated the relationship between intraoperative requirement for an inhalational anesthetic (sevoflurane) or an opioid (remifentanil) and postoperative analgesic consumption.
Methods
The study included 200 adult patients undergoing elective laparoscopic colectomy. In the sevoflurane group, the effect-site concentration of remifentanil was fixed at 1.0 ng/ml, while the inspiratory sevoflurane concentration was adjusted to maintain an appropriate anesthetic depth. In the remifentanil group, the end-expiratory sevoflurane concentration was fixed at 1.0 volume%, and the remifentanil concentration was adjusted. Pain scores and cumulative postoperative analgesic consumptions were evaluated at 2, 6, 24, and 48 h after surgery.
Results
Average end-tidal concentration of sevoflurane and effect-site concentration of remifentanil were 2.0 ± 0.4 volume% and 3.9 ± 1.4 ng/ml in the sevoflurane and remifentanil groups, respectively. Cumulative postoperative analgesic consumption at 48 h postoperatively was 55 ± 26 ml in the sevoflurane group and 57 ± 33 ml in the remifentanil group. In the remifentanil group, the postoperative cumulative analgesic consumptions at 2 and 6 h were positively correlated with intraoperative remifentanil requirements (2 h: r = 0.36, P < 0.01; 6 h: r = 0.38, P < 0.01). However, there was no significant correlation in the sevoflurane group (r = 0.04, P = 0.69).
Conclusion
The amount of intraoperative requirement of short acting opioid, remifentanil, is correlated with postoperative analgesic consumption within postoperative 6 h. It may be contributed by the development of acute opioid tolerance. However, intraoperative sevoflurane requirement had no effect on postoperative analgesic consumption.
Trial registration:
KCT0004743