bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Ground Motion Non-Gaussianity on Seismic Performance of Buildings
Authors: Ma Xingliang , Liu Zhen
Published: July 2024

The non-Gaussian feature of seismic ground motion has been reported in some works. However, there remains a lack of research on the influence of the ground motion non-Gaussianity on the seismic performance of buildings, which motivates this study. By employing a non-Gaussian non-stationary random process simulation method previously proposed by the authors, 40,000 ground motion acceleration signals are efficiently generated, including 20,000 Gaussian and 20,000 non-Gaussian records. As computational examples, a four-story frame building and a three-tower super-tall building are selected. The generated acceleration signals serve as external excitations for the two buildings, allowing for a comparison of the differences in seismic structural responses caused by the Gaussian and non-Gaussian earthquake groups. Probability analysis is performed using top-layer displacement and maximum inter-story drift ratio as damage indicators. The results show that the structural responses induced by both Gaussian and non-Gaussian earthquake groups have identical first- and second-order moments but different higher-order moments. The responses from non-Gaussian earthquakes display distinct non-Gaussian traits, with their distribution of extreme values exhibiting a longer tail compared to the Gaussian counterparts. This leads to a notably larger value of non-Gaussian responses under high crossing probabilities, with an amplification that can surpass 18%.
Incidence and Long-Term Outcomes of Biliary Tract Cancers in Olmsted County, Minnesota from 1976 to 2018
Authors: Nwankwo Eugene C. , Guta Amerti , Cao Scarlett S. , Yang Ju Dong , Abdalla Abubaker , Taha Wesam , Larson Joseph J. , Yin Jun , Gores Gregory J. , Cleary Sean P. , Roberts Lewis R.
Published: July 2024

Biliary tract cancers, including cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, rank second among hepatobiliary cancers, known for their poor prognoses. The United States has witnessed a notable increase in intrahepatic cholangiocarcinoma incidence. This study examines the incidence and survival outcomes of biliary tract cancers in Olmsted County, Minnesota from 1976 to 2018. Using data from the Rochester Epidemiology Project (REP), residents aged 20 and above were analyzed across four eras. Incidence rates were calculated and adjusted for age and sex, and temporal trends were assessed using Poisson regression. Intrahepatic cholangiocarcinoma exhibited a significant escalation in incidence rates over time, while gallbladder cancers showed a decline among women. Median survival times for biliary tract cancers notably improved. These findings confirm the rising incidence of intrahepatic cholangiocarcinoma and suggest improving survival rates. Nevertheless, the overall prognosis for biliary tract cancers remains very poor, emphasizing the continual need for enhanced management strategies and further research.
Differential miRNA and Protein Expression Reveals miR-1285, Its Targets TGM2 and CDH-1, as Well as CD166 and S100A13 as Potential New Biomarkers in Patients with Diabetes Mellitus and Pancreatic Adenocarcinoma
Authors: Kolokotronis Theodoros , Majchrzak-Stiller Britta , Buchholz Marie , Mense Vanessa , Strotmann Johanna , Peters Ilka , Skrzypczyk Lea , Liffers Sven-Thorsten , Menkene Louise Massia , Wagner Mathias , Glanemann Matthias , Betsou Fay , Ammerlaan Wim , Schmidt Ronny , Schröder Christoph , Uhl Waldemar , Braumann Chris , Höhn Philipp
Published: July 2024

Early detection of PDAC remains challenging due to the lack of early symptoms and the absence of reliable biomarkers. The aim of the present project was to identify miRNA and proteomics signatures discriminating PDAC patients with DM from nondiabetic PDAC patients. Proteomics analysis and miRNA array were used for protein and miRNA screening. We used Western blotting and Real-Time Quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) for protein and miRNA validation. Comparisons between experimental groups with normal distributions were performed using one-way ANOVA followed by Tukey’s post hoc test, and pairwise tests were performed using t-tests. p ≤ 0.05 was considered statistically significant. Protein clusters of differentiation 166 (CD166), glycoprotein CD63 (CD63), S100 calcium-binding protein A13 (S100A13), and tumor necrosis factor-β (TNF-β) were detected in the proteomics screening. The miRNA assay revealed a differential miRNA 1285 regulation. Previously described target proteins of miR-1285 cadherin-1 (CDH-1), cellular Jun (c-Jun), p53, mothers against decapentaplegic homolog 4 (Smad4), human transglutaminase 2 (TGM2) and yes-associated protein (YAP), were validated via Western blotting. miR-1285-3p was successfully validated as differentially regulated in PDAC + DM via qRT-PCR. Overall, our data suggest miRNA1285-3p, TGM2, CDH-1, CD166, and S100A13 as potential meaningful biomarker candidates to characterize patients with PDAC + DM. Data are available via ProteomeXchange with the identifier PXD053169.
Chronic Lymphocytic Leukemia: Prognostic Factors in the Era of Novel Drugs
Authors: Urso Antonio , Martino Enrica Antonia , Cuneo Antonio , Gentile Massimo , Rigolin Gian Matteo
Published: July 2024

Novel drugs have profoundly changed the outcomes in chronic lymphocytic leukemia (CLL) patients, and the traditional prognostic factors that were identified in the era of chemoimmunotherapy need to be validated in the context of these new targeted therapies. Currently, the most important prognostic genetic biomarkers are the immunoglobulin heavy chain variable (IGHV) mutational status, genetic aberrations including del(17p)/TP53 abnormalities, and the complex karyotype. In this review, we discuss the prognostic role of these genomic markers in relation to novel treatments. Moreover, we present and discuss new scoring systems that were elaborated and validated in the era of new drugs. In routine clinical practice, the application of an extensive genomic work-up with validated prognostic markers could improve the identification of “very high-risk” CLL patients who could benefit from novel, more effective targeted treatments.
N-Formylation of Carbon Dioxide and Amines with EDTA as a Recyclable Catalyst under Ambient Conditions
Authors: Zhou Qiqi , Chen Yu , Yuan Xuexin , Yang Hai-Jian , Jiang Qingqing , Hu Juncheng , Guo Cun-Yue
Published: July 2024

The reduction of CO2 is an important method to produce chemicals such as methanol, formic acid, formaldehyde, etc. In general, the reduction of CO2 is carried out at high temperatures and pressures with precious metals as catalysts, which is not favorable for industrial procedures. Thus, it will be very useful if researchers can find cost-effective catalysts for industrial application in CO2 reduction. In this work, commercially available ethylenediaminetetraacetic acid (EDTA) was tested as a cheap, non-toxic, and recyclable catalyst to initiate the N-carbonylation reaction of CO2 with amines. After screening various reaction parameters, including temperature, pressure, time, solvent, and reducing agent, the optimal reaction conditions were obtained: 80 °C, 2 MPa, 6 h, 50 mmol% catalyst dosage, 1 mL DMSO, and 1:1 molar ratio of amine to reducing agent. Notably, further studies confirmed that EDTA could also be effective for N-formylation even under ambient conditions (0.1 MPa and room temperature). The suitability of the catalyst for 26 kinds of substrates (including aliphatic amines, aromatic amines, and alicyclic amines) and its reusability were also investigated, with satisfactory results. Scale-up research has been performed effectively with a high conversion of amine (83%) to obtain the mono-formylated product selectively. Finally, the mechanism of the reaction between amine and CO2 has been proposed via control experiments and compared with results in the literature.
Diagnostic Accuracy of Non-Contrast-Enhanced Time-Resolved MR Angiography to Assess Angioarchitectural Classification Features of Brain Arteriovenous Malformations
Authors: Chauvet Grégoire , Cheddad El Aouni Mourad , Magro Elsa , Sabardu Ophélie , Ben Salem Douraied , Gentric Jean-Christophe , Ognard Julien
Published: July 2024

This study aims to assess the diagnostic accuracy of non-contrast-enhanced 4D MR angiography (NCE-4D-MRA) compared to contrast-enhanced 4D MR angiography (CE-4D-MRA) for the detection and angioarchitectural characterisation of brain arteriovenous malformations (bAVMs). Utilising a retrospective design, we examined 54 MRA pairs from 43 patients with bAVMs, using digital subtraction angiography (DSA) as the reference standard. Both NCE-4D-MRA and CE-4D-MRA were performed using a 3-T MR imaging system. The primary objectives were to evaluate the diagnostic performance of NCE-4D-MRA against CE-4D-MRA and DSA and to assess concordance between imaging modalities in grading bAVMs according to four main scales: Spetzler–Martin, Buffalo, AVM embocure score (AVMES), and R2eDAVM. Our results demonstrated that NCE-4D-MRA had a higher accuracy and specificity compared to CE-4D-MRA (0.85 vs. 0.83 and 95% vs. 85%, respectively) and similar agreement, with DSA detecting shunts in bAVMs or residuals. Concordance in grading bAVMs was substantial between NCE-4D-MRA and DSA, particularly for the Spetzler–Martin and Buffalo scales, with CE-4D-MRA showing slightly higher kappa values for interobserver agreement. The study highlights the potential of NCE-4D-MRA as a diagnostic tool for bAVMs, offering comparable accuracy to CE-4D-MRA while avoiding the risks associated with gadolinium-based contrast agents. The safety profile of imaging techniques is a significant concern in the long-term follow up of bAVMs, and further prospective research should focus on NCE-4D-MRA protocol improvement for clinical use.
Systematic Review on the Use of 3D-Printed Models for Planning, Training and Simulation in Vascular Surgery
Authors: Catasta Alexandra , Martini Chiara , Mersanne Arianna , Foresti Ruben , Bianchini Massoni Claudio , Freyrie Antonio , Perini Paolo
Published: July 2024

The use of 3D-printed models in simulation-based training and planning for vascular surgery is gaining interest. This study aims to provide an overview of the current applications of 3D-printing technologies in vascular surgery. We performed a systematic review by searching four databases: PubMed, Web of Science, Scopus, and Cochrane Library (last search: 1 March 2024). We included studies considering the treatment of vascular stenotic/occlusive or aneurysmal diseases. We included papers that reported the outcome of applications of 3D-printed models, excluding case reports or very limited case series (≤5 printed models or tests/simulations). Finally, 22 studies were included and analyzed. Computed tomography angiography (CTA) was the primary diagnostic method used to obtain the images serving as the basis for generating the 3D-printed models. Processing the CTA data involved the use of medical imaging software; 3DSlicer (Brigham and Women’s Hospital, Harvard University, Boston, MA), ITK-Snap, and Mimics (Materialise NV, Leuven, Belgium) were the most frequently used. Autodesk Meshmixer (San Francisco, CA, USA) and 3-matic (Materialise NV, Leuven, Belgium) were the most frequently employed mesh-editing software during the post-processing phase. PolyJet™, fused deposition modeling (FDM), and stereolithography (SLA) were the most frequently employed 3D-printing technologies. Planning and training with 3D-printed models seem to enhance physicians’ confidence and performance levels by up to 40% and lead to a reduction in the procedure time and contrast volume usage to varying extents.
A Research on Emotion Recognition of the Elderly Based on Transformer and Physiological Signals
Authors: Feng Guohong , Wang Hongen , Wang Mengdi , Zheng Xiao , Zhang Runze
Published: July 2024

Aiming at problems such as the difficulty of recognizing emotions in the elderly and the inability of traditional machine-learning models to effectively capture the nonlinear relationship between physiological signal data, a Recursive Map (RM) combined with a Vision Transformer (ViT) is proposed to recognize the emotions of the elderly based on Electroencephalogram (EEG), Electrodermal Activity (EDA), and Heart Rate Variability (HRV) signals. The Dung Beetle Optimizer (DBO) is used to optimize the variational modal decomposition of EEG, EDA, and HRV signals. The optimized decomposed time series signals are converted into two-dimensional images using RM, and then the converted image signals are applied to the ViT for the study of emotion recognition of the elderly. The pre-trained weights of ViT on the ImageNet-22k dataset are loaded into the model and retrained with the two-dimensional image data. The model is validated and compared using the test set. The research results show that the recognition accuracy of the proposed method on EEG, EDA, and HRV signals is 99.35%, 86.96%, and 97.20%, respectively. This indicates that EEG signals can better reflect the emotional problems of the elderly, followed by HRV signals, while EDA signals have poorer effects. Compared with Support Vector Machine (SVM), Naive Bayes (NB), and K-Nearest Neighbors (KNN), the recognition accuracy of the proposed method is increased by at least 9.4%, 11.13%, and 12.61%, respectively. Compared with ResNet34, EfficientNet-B0, and VGG16, it is increased by at least 1.14%, 0.54%, and 3.34%, respectively. This proves the superiority of the proposed method in emotion recognition for the elderly.
You Are Not Alone! Care Professionals’ Acceptance of Telemedicine in Nursing Homes Comparing Pre- and Post-Implementation Evaluations
Authors: Offermann Julia ,   Optimal@NRW Research Group, Ziefle Martina
Published: July 2024

A lack of personnel in care institutions and high proportions of older people in need of care pose central challenges for today’s aging society, often resulting in the hospitalization of geriatric patients. In many cases, these hospitalizations are not medically necessary and cause deterioration of health. Applying telemedicine in nursing homes represents one approach aimed at a reduction of unnecessary hospitalizations of geriatric patients and supporting care personnel in medically uncertain situations. For a sustainable and successful implementation of technical innovations such as telemedical consultations, the care personnel’s perspectives and acceptance are especially essential. The Optimal@NRW project implemented telemedical consultations in 24 nursing homes in Germany, investigating medical and economic efficiency and in particular also the social acceptance of digital care in nursing homes. This paper presents quantitative results comparing the acceptance evaluations before (PRE: N = 130) and after (POST: N = 87) the implementation of the telemedical consultations in the nursing homes from the perspective of care professionals. The results showed positive evaluations of the telemedical consultations in both evaluation phases: POST evaluations especially showed a lower evaluation of perceived barriers of using telemedical consultations in nursing homes. This study’s insights enable one to derive guidelines and recommendations regarding the communication and information of telemedical applications considering the needs and wishes of care personnel as a central user group.
Improved Active Disturbance Rejection Control for Permanent Magnet Synchronous Motor
Authors: Huang Zhiwei , Cheng Yuanhao , Chen Si , Zhang Xuhui , Xiang Jiawei , Wang Sun’an
Published: July 2024

To improve the control performance of a permanent magnet synchronous motor (PMSM) under external disturbances, an improved active disturbance rejection control (IADRC) algorithm is proposed. Since the nonlinear function in the conventional ADRC algorithm is not smooth enough at the breakpoints, which directly affects the control performance, an innovative nonlinear function is proposed to effectively improve the convergence and stability. On this basis, the proposed IADRC is constructed, and comparative simulation results with ADRC and other IADRC show that faster response speed, higher accuracy and stronger robustness are obtained.
Experimental and Numerical Study of Carbon Fibre-Reinforced Polymer-Strengthened Reinforced Concrete Beams under Static and Impact Loads
Authors: Mussa Mohamed H. , Mutalib Azrul A. , Hao Hong
Published: July 2024

This study aims to investigate the behaviour of reinforced concrete (RC) beams strengthened by Carbon Fibre-Reinforced Polymer (CFRP) under static and impact loads. A series of RC beams were tested and categorized into four groups, namely, unstrengthened RC beams (B1), RC beams strengthened with a CFRP longitudinal strip in the tension zone (B2), RC beams wrapped with CFRP fabric (B3), and RC beams strengthened with a combination of both CFRP longitudinal strips and wraps (B4). The results show that the average load–displacement capacity of RC beam group (B4) was improved by 84.88% as compared with the unstrengthened beam (B1) under static loads. The dynamic test results demonstrated an increase in the deflection resistance of RC beam group (B4) by −57.89% as compared with unstrengthened RC beam group (B1) under identical drop weights of 1 m. In addition, a collapse failure mode was noticed in the unstrengthened beams, while minor damage was recorded mainly in the case of RC beam group (B4). Furthermore, the numerical analysis conducted using LS-DYNA software (V 971 R6.0.0) proved that the adopted numerical models can efficiently predict the behaviour of RC beams under dynamic loads, with maximum differences reaching up to −12.5% compared with the experimental test results.
Stability or Instability of a Static Liquid Bridge Appearing in Shaped Crystal Growth from Melt via the Pulling-Down Method
Authors: Cojocaru Andreea V. , Balint Stefan
Published: July 2024

This study presents sufficient conditions for the stability or instability of the static liquid bridge appearing in crystal growth from the melt of micro-fibers, thin plates, and hollow micro-tubes of predetermined sizes using the pulling-down method. The case in which the contact angle and the growth angle verify the inequality αc>π/2−αg is considered. Experimentally, only stable static liquid bridges can be created; unstable static liquid bridges exist just in theory, because in reality they collapse. The results of this study are significant for shaped crystal growth from melted materials, with given macroscopic dimensions, and using specific equipment. This is because the obtained inequalities represent limits for what can and cannot be achieved experimentally.
Therapeutic Implication of miRNAs as an Active Regulatory Player in the Management of Pain: A Review
Authors: Hassan Mubashir , Shahzadi Saba , Yasir Muhammad , Chun Wanjoo , Kloczkowski Andrzej
Published: July 2024

Chronic pain is frequently associated with neuropathy, inflammation, or the malfunctioning of nerves. Chronic pain is associated with a significant burden of morbidity due to opioid use, associated with addiction and tolerance, and disability. MicroRNAs (miRs) are emerging therapeutic targets to treat chronic pain through the regulation of genes associated with inflammation, neuronal excitability, survival, or de-differentiation. In this review, we discuss the possible involvement of miRs in pain-related molecular pathways. miRs are known to regulate high-conviction pain genes, supporting their potential as therapeutic targets.
Vision-Specific Tools for the Assessment of Health-Related Quality of Life (HR-QoL) in Children and Adolescents with Visual Impairment: A Scoping Review
Authors: Magakwe Tshubelela Sello Simon , Hansraj Rekha , Xulu-Kasaba Zamadonda Nokuthula
Published: July 2024

Vision-related quality-of-life (QoL) measures offer a comprehensive evaluation of the impact of eye conditions and the effectiveness of treatment on important aspects of QoL. A substantial number of tools for assessing health-related quality of life (HR-QoL) in adults have been reviewed. However, despite the high prevalence of uncorrected refractive errors causing visual impairment (VI) in children, there is a notable lack of similar tools for this vulnerable population. This review aimed to systemically map evidence on the availability and use of vision-specific instruments for assessing HR-QoL in children and adolescents with VI. This review follows the Joanna Briggs Institute (JBI) guidelines (2020) and the framework by Arksey and O’Malley and Levac et al. (2010). We conducted systematic searches through databases PubMed, Science Direct, and Scopus and search platforms Web of Science and EBSCOhost to source reviews published in English from the date of their inception to December 2023. The findings are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR). We reviewed twenty tools, nine of which were developed for children in the United States and three of which were developed for children in developing countries; no tools specifically developed for children in Africa were found. In the reviewed papers, the tools were presented to children, parents, or proxies in an interview or questionnaire format. For most of the tools, reliability was assessed using internal consistency (n = 12) and test–retest reliability (n = 12). The most dominant measures of validity were construct (n = 16), content (n = 8), internal (n = 4), and criterion (n = 4). There appears to be a need for more tools developed for children in middle–low-income countries, especially for African children.
Examining Relationships between Perceptions of Air Quality—Objectively Assessed Particulate Matter—And Health-Related Attributions among Midlife and Older Adults from the San Francisco Bay Area, California, USA
Authors: Zamora Astrid N. , Campero Maria I. , Garcia Dulce M. , King Abby C.
Published: July 2024

This investigation explored (1) correlations between midlife and older adults’ air quality perceptions with objective particulate matter 2.5 (PM2.5) and diesel PM, and (2) correlations between air quality perceptions with health-related attributions among a sample of midlife and older adults (n = 66) living in or around senior affordable public housing sites in California’s San Francisco Bay Area. The adapted air quality perception scale was used to measure perceptions of air quality, while health-related attributions were obtained from the vitality plus scale (VPS), with higher values indicating worse perceptions of air quality and poorer responses to health-related attributions, respectively. Self-reported data were linked to zip code level PM2.5 and diesel PM obtained from the CalEnviroScreen 4.0. All correlations were evaluated using Spearman’s rank correlations. The mean (SD) age was 70.6 (9.1) years, and 75.7% were female. We observed moderate, positive correlations between both PM2.5 and diesel PM with three domains: perceptions related to protection measures against air quality, emotional/mental perceptions, and sensorial perceptions. We also found evidence of moderate, positive correlations between the domains of physical symptoms, perceptions related to protection measures against air quality, and emotional/mental perceptions with health-related attributions, such as sleep-related items and feelings of restlessness or agitation. Results from this exploratory study suggest that midlife and older adults’ perceptions of air quality may be moderately related to both objective air quality data and certain health behaviors and symptoms. Findings underscore the importance of considering individual perceptions as an additional area in public health strategies aimed at protecting midlife and older adults from the impacts of air pollution.
Second-Hand Tobacco Smoke Exposure: Results of Particulate Matter (PM2.5) Measurements at Hospitality Venues in Addis Ababa, Ethiopia
Authors: Hirpa Selamawit , Mdege Noreen Dadirai , Argefa Terefe Gelibo , Tefera Yifokire , Kassa Selam Abraham , Awuor Winnie , Deressa Wakgari
Published: July 2024

Introduction: In Ethiopia, a comprehensive smoke-free law that bans smoking in all public areas has been implemented since 2019. This study aimed to evaluate compliance with these laws by measuring the air quality and conducting covert observations at 154 hospitality venues (HVs) in Addis Ababa. Methods: Indoor air quality was measured using Dylos air quality monitors during the peak hours of the venues, with concentrations of particulate matter <2.5 microns in diameter (PM2.5) used as a marker of second-hand tobacco smoke. A standardized checklist was used to assess compliance with smoke-free laws during the same peak hours. The average PM2.5 concentrations were classified as good, moderate, unhealthy for sensitive groups, unhealthy for all, or hazardous using the World Health Organization’s (WHO) standard air quality index breakpoints. Results: Only 23.6% of the venues complied with all smoke-free laws indicators. Additionally, cigarette and shisha smoking were observed at the HVs. Overall, 63.9% (95% confidence interval: 56–72%) of the HVs had PM2.5 concentrations greater than 15 µg/m3. The presence of more than one cigarette smoker in the venue, observing shisha equipment in the indoor space, and the sale of tobacco products in the indoor space were significantly associated with higher median PM2.5 concentration levels (p < 0.005). Hazardous level of PM2.5 concentrations—100 times greater than the WHO standard—were recorded at HVs where several people were smoking shisha and cigarettes. Conclusions: Most HVs had PM2.5 concentrations that exceeded the WHO average air quality standard. Stricter enforcement of smoke-free laws is necessary, particularly for bars and nightclubs/lounges.
Assessment of Tie2-Rejuvenated Nucleus Pulposus Cell Transplants from Young and Old Patient Sources Demonstrates That Age Still Matters
Authors: Otani Yuto , Schol Jordy , Sakai Daisuke , Nakamura Yoshihiko , Sako Kosuke , Warita Takayuki , Tamagawa Shota , Ambrosio Luca , Munesada Daiki , Ogasawara Shota , Matsushita Erika , Kawachi Asami , Naiki Mitsuru , Sato Masato , Watanabe Masahiko
Published: July 2024

Cell transplantation is being actively explored as a regenerative therapy for discogenic back pain. This study explored the regenerative potential of Tie2+ nucleus pulposus progenitor cells (NPPCs) from intervertebral disc (IVD) tissues derived from young (<25 years of age) and old (>60 years of age) patient donors. We employed an optimized culture method to maintain Tie2 expression in NP cells from both donor categories. Our study revealed similar Tie2 positivity rates regardless of donor types following cell culture. Nevertheless, clear differences were also found, such as the emergence of significantly higher (3.6-fold) GD2 positivity and reduced (2.7-fold) proliferation potential for older donors compared to young sources. Our results suggest that, despite obtaining a high fraction of Tie2+ NP cells, cells from older donors were already committed to a more mature phenotype. These disparities translated into functional differences, influencing colony formation, extracellular matrix production, and in vivo regenerative potential. This study underscores the importance of considering age-related factors in NPPC-based therapies for disc degeneration. Further investigation into the genetic and epigenetic alterations of Tie2+ NP cells from older donors is crucial for refining regenerative strategies. These findings shed light on Tie2+ NPPCs as a promising cell source for IVD regeneration while emphasizing the need for comprehensive understanding and scalability considerations in culture methods for broader clinical applicability.
Increase in the Expression of Glucose Transporter 2 (GLUT2) on the Peripheral Blood Insulin-Producing Cells (PB-IPC) in Type 1 Diabetic Patients after Receiving Stem Cell Educator Therapy
Authors: Zhao Yong , Veysman Boris , Antolijao Kristine , Zhao Yelu , Papagni Yldalina , Wang Honglan , Ross Robin , Tibbot Terri , Povrzenic Darinka , Fox Richard
Published: July 2024

Multicenter international clinical trials demonstrated the clinical safety and efficacy by using stem cell educator therapy to treat type 1 diabetes (T1D) and other autoimmune diseases. Previous studies characterized the peripheral blood insulin-producing cells (PB-IPC) from healthy donors with high potential to give rise to insulin-producing cells. PB-IPC displayed the molecular marker glucose transporter 2 (GLUT2), contributing to the glucose transport and sensing. To improve the clinical efficacy of stem cell educator therapy in the restoration of islet β-cell function, we explored the GLUT2 expression on PB-IPC in recent onset and longstanding T1D patients. In the Food and Drug Administration (FDA)-approved phase 2 clinical studies, patients received one treatment with the stem cell educator therapy. Peripheral blood mononuclear cells (PBMC) were isolated for flow cytometry analysis of PB-IPC and other immune markers before and after the treatment with stem cell educator therapy. Flow cytometry revealed that both recent onset and longstanding T1D patients displayed very low levels of GLUT2 on PB-IPC. After the treatment with stem cell educator therapy, the percentages of GLUT2+CD45RO+ PB-IPC were markedly increased in these T1D subjects. Notably, we found that T1D patients shared common clinical features with patients with other autoimmune and inflammation-associated diseases, such as displaying low or no expression of GLUT2 on PB-IPC at baseline and exhibiting a high profile of the inflammatory cytokine interleukin (IL)-1β. Flow cytometry demonstrated that their GLUT2 expressions on PB-IPC were also markedly upregulated, and the levels of IL-1β-positive cells were significantly downregulated after the treatment with stem cell educator therapy. Stem cell educator therapy could upregulate the GLUT2 expression on PB-IPC and restore their function in T1D patients, leading to the improvement of clinical outcomes. The clinical data advances current understanding about the molecular mechanisms underlying the stem cell educator therapy, which can be expanded to treat patients with other autoimmune and inflammation-associated diseases.
Neurological Disorders Induced by Drug Use: Effects of Adolescent and Embryonic Drug Exposure on Behavioral Neurodevelopment
Authors: Karatayev Olga , Collier Adam D. , Targoff Stella R. , Leibowitz Sarah F.
Published: July 2024

Clinical studies demonstrate that the risk of developing neurological disorders is increased by overconsumption of the commonly used drugs, alcohol, nicotine and cannabis. These drug-induced neurological disorders, which include substance use disorder (SUD) and its co-occurring emotional conditions such as anxiety and depression, are observed not only in adults but also with drug use during adolescence and after prenatal exposure to these drugs, and they are accompanied by long-lasting disturbances in brain development. This report provides overviews of clinical and preclinical studies, which confirm these adverse effects in adolescents and the offspring prenatally exposed to the drugs and include a more in-depth description of specific neuronal systems, their neurocircuitry and molecular mechanisms, affected by drug exposure and of specific techniques used to determine if these effects in the brain are causally related to the behavioral disturbances. With analysis of further studies, this review then addresses four specific questions that are important for fully understanding the impact that drug use in young individuals can have on future pregnancies and their offspring. Evidence demonstrates that the adverse effects on their brain and behavior can occur: (1) at low doses with short periods of drug exposure during pregnancy; (2) after pre-conception drug use by both females and males; (3) in subsequent generations following the initial drug exposure; and (4) in a sex-dependent manner, with drug use producing a greater risk in females than males of developing SUDs with emotional conditions and female offspring after prenatal drug exposure responding more adversely than male offspring. With the recent rise in drug use by adolescents and pregnant women that has occurred in association with the legalization of cannabis and increased availability of vaping tools, these conclusions from the clinical and preclinical literature are particularly alarming and underscore the urgent need to educate young women and men about the possible harmful effects of early drug use and to seek novel therapeutic strategies that might help to limit drug use in young individuals.
Hormetic Response of Photosystem II Function Induced by Nontoxic Calcium Hydroxide Nanoparticles
Authors: Tryfon Panagiota , Sperdouli Ilektra , Moustaka Julietta , Adamakis Ioannis-Dimosthenis S. , Giannousi Kleoniki , Dendrinou-Samara Catherine , Moustakas Michael
Published: July 2024

In recent years, inorganic nanoparticles, including calcium hydroxide nanoparticles [Ca Ca(OH)2 NPs], have attracted significant interest for their ability to impact plant photosynthesis and boost agricultural productivity. In this study, the effects of 15 and 30 mg L−1 oleylamine-coated calcium hydroxide nanoparticles [Ca(OH)2@OAm NPs] on photosystem II (PSII) photochemistry were investigated on tomato plants at their growth irradiance (GI) (580 μmol photons m−2 s−1) and at high irradiance (HI) (1000 μmol photons m−2 s−1). Ca(OH)2@OAm NPs synthesized via a microwave-assisted method revealed a crystallite size of 25 nm with 34% w/w of oleylamine coater, a hydrodynamic size of 145 nm, and a ζ-potential of 4 mV. Compared with the control plants (sprayed with distilled water), PSII efficiency in tomato plants sprayed with Ca(OH)2@OAm NPs declined as soon as 90 min after the spray, accompanied by a higher excess excitation energy at PSII. Nevertheless, after 72 h, the effective quantum yield of PSII electron transport (ΦPSII) in tomato plants sprayed with Ca(OH)2@OAm NPs enhanced due to both an increase in the fraction of open PSII reaction centers (qp) and to the enhancement in the excitation capture efficiency (Fv’/Fm’) of these centers. However, the decrease at the same time in non-photochemical quenching (NPQ) resulted in an increased generation of reactive oxygen species (ROS). It can be concluded that Ca(OH)2@OAm NPs, by effectively regulating the non-photochemical quenching (NPQ) mechanism, enhanced the electron transport rate (ETR) and decreased the excess excitation energy in tomato leaves. The delay in the enhancement of PSII photochemistry by the calcium hydroxide NPs was less at the GI than at the HI. The enhancement of PSII function by calcium hydroxide NPs is suggested to be triggered by the NPQ mechanism that intensifies ROS generation, which is considered to be beneficial. Calcium hydroxide nanoparticles, in less than 72 h, activated a ROS regulatory network of light energy partitioning signaling that enhanced PSII function. Therefore, synthesized Ca(OH)2@OAm NPs could potentially be used as photosynthetic biostimulants to enhance crop yields, pending further testing on other plant species.
Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer’s Disease and Frontotemporal Dementia: A Pilot Study
Authors: Saraceno Claudia , Cervellati Carlo , Trentini Alessandro , Crescenti Daniela , Longobardi Antonio , Geviti Andrea , Bonfiglio Natale Salvatore , Bellini Sonia , Nicsanu Roland , Fostinelli Silvia , Mola Gianmarco , Riccetti Raffaella , Moretti Davide Vito , Zanetti Orazio , Binetti Giuliano , Zuliani Giovanni , Ghidoni Roberta
Published: July 2024

Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are the two major neurodegenerative diseases causing dementia. Due to similar clinical phenotypes, differential diagnosis is challenging without specific biomarkers. Beta-site Amyloid Precursor Protein cleaving enzyme 1 (BACE1) is a β-secretase pivotal in AD pathogenesis. In AD and mild cognitive impairment subjects, BACE1 activity is increased in brain/cerebrospinal fluid, and plasma levels appear to reflect those in the brain. In this study, we aim to evaluate serum BACE1 activity in FTD, since, to date, there is no evidence about its role. The serum of 30 FTD patients and 30 controls was analyzed to evaluate (i) BACE1 activity, using a fluorescent assay, and (ii) Glial Fibrillary Acid Protein (GFAP) and Neurofilament Light chain (NfL) levels, using a Simoa kit. As expected, a significant increase in GFAP and NfL levels was observed in FTD patients compared to controls. Serum BACE1 activity was not altered in FTD patients. A significant increase in serum BACE1 activity was shown in AD vs. FTD and controls. Our results support the hypothesis that serum BACE1 activity is a potential biomarker for the differential diagnosis between AD and FTD.
One-Stage Pathway from Hollongdione to C17-Alkyne and Vinyl Chloride Following Mannich Bases and Carboxylic Acid
Authors: Galimova Zarema , Smirnova Irina , Lobov Alexander , Polovyanenko Dmitriy , Rybalova Tatyana , Kazakova Oxana
Published: July 2024

Hollongdione is the first recorded example of the occurrence of a dammarane hexanor-triterpene in nature possessing antiviral and cytotoxic activity. Its simple one-stage transformation into compounds with terminal alkyne and vinyl chloride fragments via the interaction with phosphorus halides is reported. The copper(I)-catalyzed Mannich reaction of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20(21)-in 3 led to a series of aminomethylated products, while 17-carboxylic acid was obtained by ozone oxidation of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20-chloro-20(21)-en 4; the following direct amidation of the latter has been developed. The structures of all new molecules were established by spectroscopic studies that included 2D NMR correlation methods; the molecular structures of compounds 2–5 were determined by X-ray analysis.
Transcriptomic Identification of Potential C2H2 Zinc Finger Protein Transcription Factors in Pinus massoniana in Response to Biotic and Abiotic Stresses
Authors: Wang Dengbao , Qiu Zimo , Xu Tao , Yao Sheng , Chen Meijing , Li Qianzi , Agassin Romaric Hippolyte , Ji Kongshu
Published: July 2024

Biotic and abiotic stresses have already seriously restricted the growth and development of Pinus massoniana, thereby influencing the quality and yield of its wood and turpentine. Recent studies have shown that C2H2 zinc finger protein transcription factors play an important role in biotic and abiotic stress response. However, the members and expression patterns of C2H2 TFs in response to stresses in P. massoniana have not been performed. In this paper, 57 C2H2 zinc finger proteins of P. massoniana were identified and divided into five subgroups according to a phylogenetic analysis. In addition, six Q-type PmC2H2-ZFPs containing the plant-specific motif ‘QALGGH’ were selected for further study under different stresses. The findings demonstrated that PmC2H2-ZFPs exhibit responsiveness towards various abiotic stresses, including drought, NaCl, ABA, PEG, H2O2, etc., as well as biotic stress caused by the pine wood nematode. In addition, PmC2H2-4 and PmC2H2-20 were nuclear localization proteins, and PmC2H2-20 was a transcriptional activator. PmC2H2-20 was selected as a potential transcriptional regulator in response to various stresses in P. massoniana. These findings laid a foundation for further study on the role of PmC2H2-ZFPs in stress tolerance.
Cerebrovascular Involvement in Transthyretin Amyloid Cardiomyopathy
Authors: Haider Lukas , Schrutka Lore , Tommasino Emanuele , Avanzini Nicolas , Hauck Sven , Nowak Nikolaus , Hengstenberg Christian , Bonderman Diana , Thurnher Majda
Published: July 2024

Background: Intracardiac thrombosis is common in transthyretin amyloid cardiomyopathy (ATTR-CM), and patients are at risk for thromboembolic events. However, silent cerebral infarcts and the extent of cerebral small vessel disease in patients with cardiac amyloidosis are unknown. Methods: Thirty-two consecutively selected ATTR-CM patients were prospectively studied by cerebral magnetic resonance imaging (cMRI) and compared with 43 CHA2DS2-VASc-matched controls (Co). Structural clinical standard cMRI sequences and features of cerebral vessel involvement were included and quantified by two board certified neuroradiologists in consensus blinded to clinical status. Group differences were estimated using generalized (logistic) linear regression models adjusting for vascular risk factors based on the CHA2DS2-VASc score. Results: The median CHA2DS2-VASc score was 4 for ATTR-CM and Co (p = 0.905). There were no differences between groups in the frequency of current or former smokers (p = 0.755), body-mass-index > 30 (p = 0.106), and hyperlipidemia (p = 0.869). The number of territorial infarcts (4 vs. 0, p = 0.018) was higher in ATTR-CM compared to Co, as was the mean number of cerebral microbleeds (1.4 vs. 0.3, p ≤ 0.001) and the number of Virchow–Robin spaces (43.8 vs. 20.6, p ≤ 0.001). Lacunar lesion presence was higher in ATTR-CM (6 vs. 2, p = 0.054). CHA2DS2-VASc score, atrial fibrillation, anticoagulation, and the interaction term of CHA2DS2-VASc score and atrial fibrillation did not affect the probability of a territorial ischemic lesion or lacunar lesion in logistic regression modeling. Conclusions: In patients with ATTR-CM free from clinically apparent neurological symptoms, cMRI revealed unreported significant small cerebral vessel disease and territorial ischemia. Our findings may support low thresholds for anticoagulation and cMRI in patients with ATTR-CM.
Model for Predicting the Effect of Sibutramine Therapy in Obesity
Authors: Danilov Sergey D. , Matveev Georgiy A. , Babenko Alina Yu. , Shlyakhto Evgeny V.
Published: July 2024

Background: The development of models predicting response to weight loss therapy using sibutramine is found in only a few cases. The objective of the work is to develop a data-driven method of personalized recommendation for obesity treatment that would predict the response to sibutramine based on the current set of patient parameters. Methods: The decision system is built on the XGBoost classification algorithm along with recursive feature selection and Shapley data valuation. Using the results of clinical trials, it was trained to estimate the probability of overcoming a weight loss threshold. The model was evaluated by the accuracy metric using the Leave-One-Out cross-validation. Results: The model for predicting response to sibutramine treatment over 3 months has an accuracy of 71%. The model for predicting outcomes at the sixth month visit based on results at 3 months has an accuracy of 80%. Conclusions: Although our developed prediction model may not exhibit high precision compared to certain benchmarks, it significantly outperforms random chance or models relying only on BMI parameters. Our model used the available range of laboratory tests, which makes it possible to use this model for routine clinical use and help doctors decide whether to prescribe sibutramine.
Identification of Time-Series Pattern Marker in Its Application to Mortality Analysis of Pneumonia Patients in Intensive Care Unit
Authors: Lee Suhyeon , Kim Suhyun , Koh Gayoun , Ahn Hongryul
Published: July 2024

Electronic Health Records (EHRs) are a significant source of big data used to track health variables over time. The analysis of EHR data can uncover medical markers or risk factors, aiding in the diagnosis and monitoring of diseases. We introduce a novel method for identifying markers with various temporal trend patterns, including monotonic and fluctuating trends, using machine learning models such as Long Short-Term Memory (LSTM). By applying our method to pneumonia patients in the intensive care unit using the MIMIC-III dataset, we identified markers exhibiting both monotonic and fluctuating trends. Specifically, monotonic markers such as red cell distribution width, urea nitrogen, creatinine, calcium, morphine sulfate, bicarbonate, sodium, troponin T, albumin, and prothrombin time were more frequently observed in the mortality group compared to the recovery group throughout the 10-day period before discharge. Conversely, fluctuating trend markers such as dextrose in sterile water, polystyrene sulfonate, free calcium, and glucose were more frequently observed in the mortality group as the discharge date approached. Our study presents a method for detecting time-series pattern markers in EHR data that respond differently according to disease progression. These markers can contribute to monitoring disease progression and enable stage-specific treatment, thereby advancing precision medicine.
Study on Low-Velocity Impact and Residual Compressive Mechanical Properties of Carbon Fiber–Epoxy Resin Composites
Authors: Qiang Xueyuan , Wang Te , Xue Hua , Ding Jun , Deng Chengji
Published: July 2024

Room temperature drop hammer impact and compression after impact (CAI) experiments were conducted on carbon fiber–epoxy resin (CF/EP) composites to investigate the variation in impact load and absorbed energy, as well as to determine the residual compressive strength of CF/EP composites following impact damage. Industrial CT scanning was employed to observe the damage morphology after both impact and compression, aiding in the study of impact-damage and compression-failure mechanisms. The results indicate that, under the impact load, the surface of a CF/EP composite exhibits evident cratering as the impact energy increases, while cracks form along the length direction on the back surface. The residual compressive strength exhibits an inverse relationship with the impact energy. Impact damage occurring at an energy lower than 45 J results in end crushing during the compression of CF/EP composites, whereas energy exceeding 45 J leads to the formation of long cracks spanning the entire width of the specimen, primarily distributed symmetrically along the center of the specimen.
Iron Loss and Temperature Rise Analysis of a Transformer Core Considering Vector Magnetic Hysteresis Characteristics under Direct Current Bias
Authors: Shi Minxia , Li Teng , Yuan Shuai , Zhang Leran , Ma Yuzheng , Gao Yi
Published: July 2024

Direct current (DC) bias induced by the DC transmission and geomagnetically induced current is a critical factor in the abnormal operation of electrical equipment and is widely used in the field of power transmission and distribution system state evaluation. As the main affected component, the vector magnetization state of a transformer core under DC bias has rarely been studied, resulting in inaccurate transformer operation state estimations. In this paper, a dynamic vector hysteresis model that considers the impact of rotating and DC-biased fields is introduced into the numerical analysis to simulate the distribution of magnetic properties, iron loss and temperature of the transformer core model and a physical 110 kV single-phase autotransformer core. The maximum values of B, H and iron loss exist at the corners and T-joint of the core under rotating and DC-biased fields. The corresponding maximum value of the temperature increase is found in the main core limb area. The temperature rise of the 110 kV transformer core under various DC-biased conditions is measured and compared with the FEM (Finite Element Method) results of the proposed model and the model solely based on the magnetization curve B||H. The calculation error of the temperature rise obtained by the improved model is approximately 3.76–15.73% and is much less than the model solely based on magnetization curve B||H (approximately 50.71–66.92%).