bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Two Bacterial Characterization Techniques for the Genomic Analysis of River Microbiomes
Authors: Bonnelly Roberto , Calderon Victor V. , Ortiz Irene , Ovando Argeny , Pinales Confesora , Lara Willy , Mateo-Perez Santo E. , Cardenas-Alegria Oscar , Ramos Rommel T. , Rodríguez-Rodríguez Yaset , Martín Luis O. Maroto , Franco Edian F.
Published: September 2023

This study compares the feasibility of matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry with whole genome sequencing (WGS) for identifying bacteria in river surface water samples. We collected samples from four rivers in the Dominican Republic and used both techniques to characterize bacterial profiles. MALDI-TOF demonstrated high precision, with 86.2% similarity to WGS results, except for a few discordant cases due to database limitations. MALDI-TOF provided cost-effective and rapid identification, making it a promising alternative to WGS in resource-constrained regions. In particular, good effectiveness of MALDI-TOF in identifying bacteria with a high probability of being resistant to antibiotics was observed, which allows this technology to be used in the monitoring processes of this type of microorganism for their rapid, accurate, and low-cost identification. We found this technology to be advantageous for environmental bacterial profiling, with potential applications in understanding waterborne pathogenic bacteria. Our findings underline the relevance of MALDI-TOF in microbiology and its potential to expand its capabilities in bacterial identification and protein profiling.
Non-Fungible Tokens and Select Art Law Considerations
Authors: Ekinci Zeynep
Published: September 2023

Since 2021, non-fungible tokens (NFTs) have been a popular topic which has kindled the interest of art and technology enthusiasts and professionals. Some had very high expectations for the potential of NFTs, and in some cases, made an assessment for NFTs that go beyond the existing limits of NFTs. There have also been others who approached NFTs suspiciously and in some cases, described them as a hoax. The purpose of this study is to examine the important effects of NFTs on the art world and art law, and to consider NFTs’ current and potential impacts. In this context, this article first provides an introduction to NFTs and why the author finds it interesting to think about legal issues surrounding NFTs. After providing definitions of non-fungible tokens and highlighting technical aspects of NFTs, the article then discusses select legal issues surrounding NFTs, such as the importance of legal terms and conditions of an NFT purchase, legal qualifications of NFTs, artwork ownership, artwork authenticity, artwork provenance and intermediary liability for NFT sales. One of the aims of this study is to put forward clearly what should be expected of non-fungible tokens and their potential. Another objective is to underline the fact that the unique dynamics of the art world necessitate having a unique perspective for legal matters relating to them, which is satisfied with art law and its professionals. Ultimately, this paper aims to contribute to having a more comprehensive understanding of non-fungible tokens and their impact on the art world and surrounding legal questions.
Influence of Key Climate Factors on Desertification in Inner Mongolia
Authors: Liu Zhihui , Ma Long , Liu Tingxi , Qiao Zixu , Chen Yang
Published: September 2023

Desertification is a major environmental problem facing the world today, and climate change is an important factor influencing desertification. This study investigates the impact of changes in key climate factors on desertification based on normalized difference vegetation index data, precipitation data and evaporation data from Inner Mongolia between 1982 and 2020 using correlation analysis, regression modelling, and residual analysis. The results show that precipitation and evaporation are significantly correlated with mild desertification and severe desertification, respectively, with correlation coefficients reaching 0.98 and −0.96, respectively. In severely desertified areas in central-eastern Inner Mongolia, there is a high correlation between desertification and temperature, the characteristics of the correlation of average maximum and minimum temperatures with desertification are similar to those of the correlation of average temperature with desertification, and the average maximum and minimum temperatures are well correlated with mild desertification, with correlation coefficients as high as 0.98 and 0.978, respectively. Climate contribution accounts for 97% of desertification in severely desertified areas, indicating that climate change has increased desertification in these areas. In regions with improved desertification, approximately 75% are primarily influenced by climate change (with a relative contribution greater than 50%), with climate factors exhibiting a relative contribution greater than 75% to desertification in 30% of these regions.
CloudY-Net: A Deep Convolutional Neural Network Architecture for Joint Segmentation and Classification of Ground-Based Cloud Images
Authors: Hu Feiyang , Hou Beiping , Zhu Wen , Zhu Yuzhen , Zhang Qinlong
Published: September 2023

Ground-based cloud images contain a wealth of cloud information and are an important part of meteorological research. However, in practice, ground cloud images must be segmented and classified to obtain the cloud volume, cloud type and cloud coverage. Existing methods ignore the relationship between cloud segmentation and classification, and usually only one of these is studied. Accordingly, our paper proposes a novel method for the joint classification and segmentation of cloud images, called CloudY-Net. Compared to the basic Y-Net framework, which extracts feature maps from the central layer, we extract feature maps from four different layers to obtain more useful information to improve the classification accuracy. These feature maps are combined to produce a feature vector to train the classifier. Additionally, the multi-head self-attention mechanism is implemented during the fusion process to enhance the information interaction among features further. A new module called Cloud Mixture-of-Experts (C-MoE) is proposed to enable the weights of each feature layer to be automatically learned by the model, thus improving the quality of the fused feature representation. Correspondingly, experiments are conducted on the open multi-modal ground-based cloud dataset (MGCD). The results demonstrate that the proposed model significantly improves the classification accuracy compared to classical networks and state-of-the-art algorithms, with classification accuracy of 88.58%. In addition, we annotate 4000 images in the MGCD for cloud segmentation and produce a cloud segmentation dataset called MGCD-Seg. Then, we obtain a 96.55 mIoU on MGCD-Seg, validating the efficacy of our method in ground-based cloud imagery segmentation and classification.
Investigating Whether the Ensemble Average of Multi-Global-Climate-Models Can Necessarily Better Project Seasonal Drought Conditions in China
Authors: Liu Jinping , Ren Yanqun , Willems Patrick , Liu Tie , Yong Bin , Shalamzari Masoud Jafari , Gao Huiran
Published: September 2023

Global drought patterns are substantially impacted by climate change, with far-reaching implications for socioeconomic and ecological systems. Existing global climate models (GCMs) are unable to accurately project precipitation and drought characteristics, particularly in countries or regions with complex topography and significant seasonal variability, such as China. Consequently, the purpose of this study is to assess the efficacy of GCMs, and their multi-model ensemble mean, as well as to investigate the seasonal drought characteristics in China using precipitation data from CMIP6 under various “possible future” scenarios. This study selected five GCMs with historical (1961–2014) and future (2015–2100) periods, namely CNRM-CM6-1, GFDL-ESM4, MPI-ESM1-2-HR, MPI-ESM1-2-LR, and NorESM2-MM, as well as their ensemble mean ENS-CGMMN. Based on the China Daily Precipitation Analysis Product (CPAP) as the reference precipitation, the performance of these models is evaluated using the DISO index and the quantile mapping (QM) method for calibration, as well as seasonal-scale drought using the standardized precipitation index (SPI) and spatiotemporal variability analysis methods. In comparison to other climate models and the ensemble mean, the calibrated MPI-ESM1-2-HR model can more precisely describe the actual precipitation conditions at the seasonal scale. Under four scenarios, China’s climate will shift from arid to moist in the future period (2015–2100) (SSP126, SSP245, SSP370, and SSP585). Autumn and summer will see a considerable increase in China’s moisture levels. During the autumn, winter, and spring, the moisture will generally increase in the northern subregions of China, including the Qinghai-Tibet Plateau (QTP), Xinjiang (XJ), Northwest (NW), Northeast (NE), and North China (NC). Dryness will decrease in southern subregions, such as the Southwest (SW) and South China (SC). In contrast to these three seasons, summer in XJ exhibits a distinct trend of aridity, especially in the SSP245 scenario, whereas the NE, NC, and SC exhibit a distinct trend of moisture. To be more specific, the aridity changes in subregions during various seasons under different future climate scenarios vary significantly. This study’s findings can provide significant support for future research on climate change and drought, which can help improve the accuracy of future climate projections and serve as a reference for drought risk management and policy formulation.
Cochlear Function in Individuals with and without Spontaneous Otoacoustic Emissions
Authors: Mo Changgeng , McPherson Bradley , Ma Ting-Fung
Published: September 2023

Purpose: This study investigated the status of spontaneous otoacoustic emissions (SOAEs) on cochlear function in a cohort of male/female participants with a wide age range. It examined whether there was a correlation between the presence of SOAEs and measurements of transient evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), SOAEs and extended high-frequency (EHF) hearing thresholds. Methods: 463 participants (222 male, 241 female; age range 20–59 years) with pure-tone thresholds ≤25 dB HL for octave frequencies of 500–8000 Hz were included in the study, divided into three age groups (20–29, 30–39, and 40–59 years). Evaluations included EHF (9000–16,000 Hz) hearing thresholds and TEOAE, DPOAE and SOAE measures. Results: Multiple regression models showed that participants with SOAEs had larger expected amplitudes and signal-to-noise ratios (SNRs) for TEOAE and DPOAE responses than participants without SOAEs, holding gender and age variables constant. Spearman correlation tests identified deterioration in TEOAE and DPOAE amplitudes and SNRs, and EHF hearing thresholds with age in participants without SOAEs. Among participants with SOAEs, no significant decreases in TEOAE and DPOAE measures were shown in participants with older age. Nonetheless, as expected, EHF hearing thresholds did become worse with age, with or without SOAEs. Conclusions: Participants with identifiable SOAEs had greater TEOAE and DPOAE amplitudes and SNRs than participants without SOAEs. SOAEs appear to be a useful marker of cochlear health in adults.
Investigating the Effect of Different Bidirectional Pulsed Current Parameters on the Heat Generation of Lithium-Ion Battery at Low Temperatures
Authors: Huang Ranjun , Wei Gang , Jiang Bo , Zhu Jiangong , Pan Xiangmin , Wang Xueyuan , Zhou Xiangyang , Ye Jiping , Wei Xuezhe , Dai Haifeng
Published: September 2023

Bidirectional pulsed current (BPC) heating has proven to be an effective method for internal heating. However, current research has primarily focused on the impact of symmetrical BPC on battery heat generation, while neglecting the influence of different BPC parameters. To address this gap, this paper investigates the effects of various BPC parameters on battery heat generation. Initially, an electro-thermal coupled model of the battery is constructed based on the results of electrochemical impedance spectroscopy (EIS) tests conducted at different temperatures and amplitudes at 20% state of charge (SOC). The validation results of the model demonstrate that the absolute errors of voltage and temperature are generally less than 50 mV and 1.2 °C. Subsequently, the influence of BPC parameters on battery heat generation is examined under different terminal voltage constraints, temperatures, and frequencies. The findings at 20% SOC reveal that symmetrical BPC does not consistently correspond to the maximum heating power. The proportion of charge time and discharge time in one cycle, corresponding to the maximum heating power, varies depending on the charge and discharge cut-off voltages. Moreover, these variations differ across frequencies and temperatures. When the terminal voltage is constrained between 3 V and 4.2 V, the maximum heat power corresponds to a discharge time share of 0.55 in one cycle. In conclusion, the results underscore the complex relationship between BPC parameters and battery heat generation, which can further enhance our understanding of effective heating strategies for batteries.
Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites
Authors: Später Thomas , Kaneda Giselle , Chavez Melissa , Sheyn Julia , Wechsler Jacob , Yu Victoria , Del Rio Patricia , Huang Dave , Metzger Melodie , Tawackoli Wafa , Sheyn Dmitriy
Published: September 2023

In regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger strong inflammatory host responses, other studies report antibody formation and immune rejection following xenotransplantation. Accordingly, the goal of our study was to test the cellular retention and survival of human-induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) and primary nucleus pulposus cells (NPCs) following their xenotransplantation into immune-privileged knee joints (14 days) and intervertebral discs (IVD; 7 days) of immunocompromised Nude and immunocompetent Sprague Dawley (SD) rats. At the end of both experiments, we could demonstrate that both rat types revealed comparably low levels of systemic IL-6 and IgM inflammation markers, as assessed via ELISA. Furthermore, the number of recovered cells was with no significant difference between both rat types. Conclusively, our results show that xenogeneic injection of human iMSC and NPC into immunoprivileged knee and IVD sites did not lead to an elevated inflammatory response in immunocompetent rats when compared to immunocompromised rats. Hence, immunocompetent rats represent suitable animals for xenotransplantation studies targeting immunoprivileged sites.
Transcriptomic Analysis of Light-Induced Genes in Nasonia vitripennis: Possible Implications for Circadian Light Entrainment Pathways
Authors: Wang Yifan , Beukeboom Leo W. , Wertheim Bregje , Hut Roelof A.
Published: September 2023

Circadian entrainment to the environmental day–night cycle is essential for the optimal use of environmental resources. In insects, opsin-based photoreception in the compound eye and ocelli and CRYPTOCHROME1 (CRY1) in circadian clock neurons are thought to be involved in sensing photic information, but the genetic regulation of circadian light entrainment in species without light-sensitive CRY1 remains unclear. To elucidate a possible CRY1-independent light transduction cascade, we analyzed light-induced gene expression through RNA-sequencing in Nasonia vitripennis. Entrained wasps were subjected to a light pulse in the subjective night to reset the circadian clock, and light-induced changes in gene expression were characterized at four different time points in wasp heads. We used co-expression, functional annotation, and transcription factor binding motif analyses to gain insight into the molecular pathways in response to acute light stimulus and to form hypotheses about the circadian light-resetting pathway. Maximal gene induction was found after 2 h of light stimulation (1432 genes), and this included the opsin gene opblue and the core clock genes cry2 and npas2. Pathway and cluster analyses revealed light activation of glutamatergic and GABA-ergic neurotransmission, including CREB and AP-1 transcription pathway signaling. This suggests that circadian photic entrainment in Nasonia may require pathways that are similar to those in mammals. We propose a model for hymenopteran circadian light-resetting that involves opsin-based photoreception, glutamatergic neurotransmission, and gene induction of cry2 and npas2 to reset the circadian clock.
Flaxseed Supplementation in Chicken Feed Accelerates Salmonella enterica subsp. enterica Serovar Enteritidis Clearance, Modulates Cecum Microbiota, and Influences Ovarian Gene Expression in Laying Hens
Authors: Wang De , Ma Boheng , Liao Ziwei , Li Wenjing , Zhang Tiejun , Lei Changwei , Wang Hongning
Published: September 2023

Salmonella is a foodborne pathogen that poses a serious threat to both human and animal health and food safety. Flaxseed is rich in unsaturated fatty acids; has anti-metabolic syndrome, anti-inflammatory, and neuroprotective properties; and may be a potential source of feed additives. To investigate the impact of flaxseed on Salmonella-infected laying hens, we administered Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) after adding flaxseed to the feed of laying hens (15% [750 mg/kg]). S. Enteritidis colonization was reduced and its clearance was accelerated from the laying hens. Furthermore, flaxseed supplementation mitigated the damage to the ileum caused by S. Enteritidis. We analyzed alterations in intestinal flora through 16S rRNA amplicon sequencing. S. Enteritidis infection increased the abundance of Akkermansia and triggered the host inflammatory response. Conversely, the addition of flaxseed to the feed increased the abundance of beneficial intestinal bacteria, such as Lactobacilli and Bacteroides. Ovarian health is important for egg production performance in laying hens and our findings indicate that S. Enteritidis can persist in the ovaries for an extended period. Therefore, we further performed transcriptome sequencing analysis of ovarian tissues on day seven after S. Enteritidis infection. S. Enteritidis infection leads to altered ovarian gene expression, including the downregulation of lipid metabolism and growth and development genes and the upregulation of host immune response genes in laying hens. The upregulation of genes associated with growth and development may have stimulated ovarian growth and development.
The Effect of SERCA Activation on Functional Characteristics and Signaling of Rat Soleus Muscle upon 7 Days of Unloading
Authors: Sharlo Kristina A. , Lvova Irina D. , Tyganov Sergey A. , Zaripova Ksenia A. , Belova Svetlana P. , Kostrominova Tatiana Y. , Shenkman Boris S. , Nemirovskaya Tatiana L.
Published: September 2023

Skeletal muscle abnormalities and atrophy during unloading are accompanied by the accumulation of excess calcium in the sarcoplasm. We hypothesized that calcium accumulation may occur, among other mechanisms, due to the inhibition of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity. Consequently, the use of the SERCA activator will reduce the level of calcium in the sarcoplasm and prevent the negative consequences of muscle unloading. Wistar rats were randomly assigned into one of three groups (eight rats per group): control rats with placebo (C), 7 days of unloading/hindlimb suspension with placebo (7HS), and 7 days of unloading treated with SERCA activator CDN1163 (7HSC). After seven days of unloading the soleus muscle, the 7HS group displayed increased fatigue in the ex vivo test, a significant increase in the level of calcium-dependent CaMK II phosphorylation and the level of tropomyosin oxidation, as well as a decrease in the content of mitochondrial DNA and protein, slow-type myosin mRNA, and the percentage of slow-type muscle fibers. All of these changes were prevented in the 7HSC group. Moreover, treatment with CDN1163 blocked a decrease in the phosphorylation of p70S6k, an increase in eEF2 phosphorylation, and an increase in MuRF-1 mRNA expression. Nevertheless, there were no differences in the degree of fast and slow muscle fiber atrophy between the 7HS and 7HSC groups. Conclusion: SERCA activation during 7 days of unloading prevented an increase in soleus fatigue, the decrease of slow-type myosin, mitochondrial markers, and markers of calcium homeostasis but had no effect on muscle atrophy.
The Potential Mechanisms behind Loperamide-Induced Cardiac Arrhythmias Associated with Human Abuse and Extreme Overdose
Authors: Lu Hua Rong , Damiano Bruce P. , Kreir Mohamed , Rohrbacher Jutta , van der Linde Henk , Saidov Tamerlan , Teisman Ard , Gallacher David J.
Published: September 2023

Loperamide has been a safe and effective treatment for diarrhea for many years. However, many cases of cardiotoxicity with intentional abuse of loperamide ingestion have recently been reported. We evaluated loperamide in in vitro and in vivo cardiac safety models to understand the mechanisms for this cardiotoxicity. Loperamide slowed conduction (QRS-duration) starting at 0.3 µM [~1200-fold (×) its human Free Therapeutic Plasma Concentration; FTPC] and reduced the QT-interval and caused cardiac arrhythmias starting at 3 µM (~12,000× FTPC) in an isolated rabbit ventricular-wedge model. Loperamide also slowed conduction and elicited Type II/III A-V block in anesthetized guinea pigs at overdose exposures of 879× and 3802× FTPC. In ion-channel studies, loperamide inhibited hERG (IKr), INa, and ICa currents with IC50 values of 0.390 µM, 0.526 µM, and 4.091 µM, respectively (i.e., >1560× FTPC). Additionally, in silico trials in human ventricular action potential models based on these IC50s confirmed that loperamide has large safety margins at therapeutic exposures (≤600× FTPC) and confirmed repolarization abnormalities in the case of extreme doses of loperamide. The studies confirmed the large safety margin for the therapeutic use of loperamide but revealed that at the extreme exposure levels observed in human overdose, loperamide can cause a combination of conduction slowing and alterations in repolarization time, resulting in cardiac proarrhythmia. Loperamide’s inhibition of the INa channel and hERG-mediated IKr are the most likely basis for this cardiac electrophysiological toxicity at overdose exposures. The cardiac toxic effects of loperamide at the overdoses could be aggravated by co-medication with other drug(s) causing ion channel inhibition.
Signaling Mechanisms of Stem Cell Therapy for Intervertebral Disc Degeneration
Authors: Du Xiaotian , Liang Kejiong , Ding Shili , Shi Haifei
Published: September 2023

Low back pain is the leading cause of disability worldwide. Intervertebral disc degeneration (IDD) is the primary clinical risk factor for low back pain and the pathological cause of disc herniation, spinal stenosis, and spinal deformity. A possible approach to improve the clinical practice of IDD-related diseases is to incorporate biomarkers in diagnosis, therapeutic intervention, and prognosis prediction. IDD pathology is still unclear. Regarding molecular mechanisms, cellular signaling pathways constitute a complex network of signaling pathways that coordinate cell survival, proliferation, differentiation, and metabolism. Recently, stem cells have shown great potential in clinical applications for IDD. In this review, the roles of multiple signaling pathways and related stem cell treatment in IDD are summarized and described. This review seeks to investigate the mechanisms and potential therapeutic effects of stem cells in IDD and identify new therapeutic treatments for IDD-related disorders.
Reduced Lipid Peroxidation Predicts Unfavorable Prognosis in Hepatocellular Carcinoma, but Not Intrahepatic Cholangiocarcinoma
Authors: Gerber Tiemo Sven , Witzel Hagen Roland , Weinmann Arndt , Bartsch Fabian , Schindeldecker Mario , Galle Peter R. , Lang Hauke , Roth Wilfried , Ridder Dirk Andreas , Straub Beate Katharina
Published: September 2023

Primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a significant contributor to cancer-related mortality worldwide. Oxidative stress and lipid peroxidation play a key role in chronic liver diseases and have been shown to be pivotal for tumor initiation and progression. 4-hydroxy-nonenal (4-HNE), one of the major mediators of oxidative stress and a well-established biomarker for lipid peroxidation, can act as a signal transducer, inducing inflammation and exerting carcinogenic effects. However, the role of 4-HNE in primary liver cancer remains poorly explored. In this study, we investigated 4-HNE levels in 797 liver carcinomas, including 561 HCC and 236 iCCA, by immunohistochemistry. We then correlated 4-HNE levels with comprehensive clinical data and survival outcomes. In HCC, lower expression levels of 4-HNE were associated with vascular invasion, a high tumor grade, a macrotrabecular-massive HCC subtype, and poor overall survival. Concerning iCCA, large duct iCCA showed significantly higher 4-HNE levels when compared to small duct iCCA. Yet, in iCCA, 4-HNE levels did not correlate with known prognostic parameters or survival outcomes. To conclude, in HCC but not in iCCA, low amounts of 4-HNE predict unfavorable survival outcomes and are associated with aggressive tumor behavior. These findings provide insights into the role of 4-HNE in liver cancer progression and may enable novel therapeutic strategies.
Comprehensive Analysis Identifies PKP3 Overexpression in Pancreatic Cancer Related to Unfavorable Prognosis
Authors: Du Yan , Hou Shuang , Chen Zhou , Li Wancheng , Li Xin , Zhou Wence
Published: September 2023

Plakophilin 3 (PKP3) affects cell signal transduction and cell adhesion and performs a crucial function in tumorigenesis. The current investigation evaluated the predictive significance and underlying processes of PKP3 within pancreatic cancer (PC) tissues. The assessment of differences in PKP3 expression was conducted through an analysis of RNA-seq data acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, clinical samples were collected to validate the findings. The predictive significance of PKP3 was investigated by analyzing survival data derived from TCGA and clinical specimens. PKP3′s biological function was assessed via phenotypic experiments after the suppression of PKP3 expression within PC cells. Functional enrichment analysis, encompassing KEGG, GO, and GSEA, was employed to assess the underlying mechanism of PKP3. Immune infiltration analysis was conducted in the present investigation to determine the association between PKP3 and tumor-infiltrating immune cells (TICs). In PC tissues, PKP3 expression was abnormally upregulated and correlated with a negative prognosis in individuals with PC. PKP3 can promote the progression, migration, and invasive capacity of PC cells and is relevant to the regulation of the PI3K–Akt and MAPK signaling pathways. Immune infiltration analysis demonstrated that PKP3 impeded CD8+ T-cell infiltration and immune cytokine expression within the tumor microenvironment. The PKP3 protein was identified as a prospective independent predictive indicator and represents a viable approach for immunotherapy in the context of PC. PKP3 may impact prognosis by broadly inhibiting immune cell infiltration and promoting the activation of tumor-associated signaling pathways.
Role of Cardio-Renal Dysfunction, Inflammation Markers, and Frailty on In-Hospital Mortality in Older COVID-19 Patients: A Cluster Analysis
Authors: Spannella Francesco , Giulietti Federico , Laureti Giorgia , Di Rosa Mirko , Di Pentima Chiara , Allevi Massimiliano , Garbuglia Caterina , Giordano Piero , Landolfo Matteo , Ferrara Letizia , Fumagalli Alessia , Lattanzio Fabrizia , Bonfigli Anna Rita , Sarzani Riccardo
Published: September 2023

Our study aimed to identify clusters of hospitalized older COVID-19 patients according to their main comorbidities and routine laboratory parameters to evaluate their association with in-hospital mortality. We performed an observational study on 485 hospitalized older COVID-19 adults (aged 80+ years). Patients were aggregated in clusters by a K-medians cluster analysis. The primary outcome was in-hospital mortality. Medical history and laboratory parameters were collected on admission. Frailty, defined by the Clinical Frailty Scale (CFS), referred to the two weeks before hospitalization and was used as a covariate. The median age was 87 (83–91) years, with a female prevalence (59.2%). Three different clusters were identified: cluster 1 (337), cluster 2 (118), and cluster 3 (30). In-hospital mortality was 28.5%, increasing from cluster 1 to cluster 3: cluster 1 = 21.1%, cluster 2 = 40.7%, and cluster 3 = 63.3% (p < 0.001). The risk for in-hospital mortality was higher in clusters 2 [HR 1.96 (95% CI: 1.28–3.01)] and 3 [HR 2.87 (95% CI: 1.62–5.07)] compared to cluster 1, even after adjusting for age, sex, and frailty. Patients in cluster 3 were older and had a higher prevalence of atrial fibrillation, higher admission NT-proBNP and C-reactive protein levels, higher prevalence of concurrent bacterial infections, and lower estimated glomerular filtration rates. The addition of CFS significantly improved the predictive ability of the clusters for in-hospital mortality. Our cluster analysis on older COVID-19 patients provides a characterization of those subjects at higher risk for in-hospital mortality, highlighting the role played by cardio-renal impairment, higher inflammation markers, and frailty, often simultaneously present in the same patient.
Contributions to the Dynamic Regime Behavior of a Bionic Leg Prosthesis
Authors: Drăgoi Marius-Valentin , Hadăr Anton , Goga Nicolae , Baciu Florin , Ștefan Amado , Grigore Lucian Ștefăniță , Gorgoteanu Damian , Molder Cristian , Oncioiu Ionica
Published: September 2023

The purpose of prosthetic devices is to reproduce the angular-torque profile of a healthy human during locomotion. A lightweight and energy-efficient joint is capable of decreasing the peak actuator power and/or power consumption per gait cycle, while adequately meeting profile-matching constraints. The aim of this study was to highlight the dynamic characteristics of a bionic leg with electric actuators with rotational movement. Three-dimensional (3D)-printing technology was used to create the leg, and servomotors were used for the joints. A stepper motor was used for horizontal movement. For better numerical simulation of the printed model, three mechanical tests were carried out (tension, compression, and bending), based on which the main mechanical characteristics necessary for the numerical simulation were obtained. For the experimental model made, the dynamic stresses could be determined, which highlights the fact that, under the conditions given for the experimental model, the prosthesis resists.
Targeted Strategies for Degradation of Key Transmembrane Proteins in Cancer
Authors: Sakanyan Vehary , Iradyan Nina , Alves de Sousa Rodolphe
Published: September 2023

Targeted protein degradation is an attractive technology for cancer treatment due to its ability to overcome the unpredictability of the small molecule inhibitors that cause resistance mutations. In recent years, various targeted protein degradation strategies have been developed based on the ubiquitin–proteasome system in the cytoplasm or the autophagy–lysosomal system during endocytosis. In this review, we describe and compare technologies for the targeted inhibition and targeted degradation of the epidermal growth factor receptor (EGFR), one of the major proteins responsible for the onset and progression of many types of cancer. In addition, we develop an alternative strategy, called alloAUTO, based on the binding of new heterocyclic compounds to an allosteric site located in close proximity to the EGFR catalytic site. These compounds cause the targeted degradation of the transmembrane receptor, simultaneously activating both systems of protein degradation in cells. Damage to the EGFR signaling pathways promotes the inactivation of Bim sensor protein phosphorylation, which leads to the disintegration of the cytoskeleton, followed by the detachment of cancer cells from the extracellular matrix, and, ultimately, to cancer cell death. This hallmark of targeted cancer cell death suggests an advantage over other targeted protein degradation strategies, namely, the fewer cancer cells that survive mean fewer chemotherapy-resistant mutants appear.
An Evaluation of the Effectiveness of Repetitive Transcranial Magnetic Stimulation (rTMS) for the Management of Treatment-Resistant Depression with Somatic Attributes: A Hospital-Based Study in Oman
Authors: Al-Ruhaili Intisar , Al-Huseini Salim , Al-Kaabi Said , Mahadevan Sangeetha , Al-Sibani Nasser , Al Balushi Naser , Islam M. Mazharul , Jose Sachin , Mehr Gilda Kiani , Al-Adawi Samir
Published: September 2023

Depressive illnesses in non-Western societies are often masked by somatic attributes that are sometimes impervious to pharmacological agents. This study explores the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for people experiencing treatment-resistant depression (TRD) accompanied by physical symptoms. Data were obtained from a prospective study conducted among patients with TRD and some somatic manifestations who underwent 20 sessions of rTMS intervention from January to June 2020. The Hamilton Rating Scale for Depression (HAMD) was used for clinical evaluation. Data were analysed using descriptive and inferential techniques (multiple logistic regression) in SPSS. Among the 49 participants (mean age: 42.5 ± 13.3), there was a significant reduction in posttreatment HAMD scores compared to baseline (t = 10.819, p < 0.0001, and 95% CI = 8.574–12.488), indicating a clinical response. Approximately 37% of the patients responded to treatment, with higher response rates among men and those who remained in urban areas, had a history of alcohol use, and were subjected to the standard 10 HZ protocol. After adjusting for all extraneous variables, the rTMS protocol emerged as the only significant predictor of response to the rTMS intervention. To our knowledge, this is the first study to examine the effectiveness of rTMS in the treatment of somatic depression.
A New Factor “Otherism” Added to the Hedonic and Eudaimonic Motives for Activities Scale (HEMA) in Chinese Culture
Authors: Dong Rong , Wang Yunxi , Wei Chenguang , Hou Xiangling , Ju Kang , Liang Yiming , Xi Juzhe
Published: September 2023

Due to different understandings of happiness, people adopt different tendencies to act, which is called orientation to happiness (OTH). Our previous study found that OTH had two core themes, Self-focused and Other-focused in Chinese culture, which was different from OTH structures in Western culture. However, no corresponding measurement tool has been developed or revised. The Hedonic and Eudaimonic Motives for Activities Scale (HEMA) was the most commonly used measurement tool of OTH in recent years. The present study aimed to develop a Chinese version of the HEMA. A total of 1729 Chinese adults participated in this study. The exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the underlying structure of the Chinese version of the HEMA. The results supported the 3-factor structure of the translation instrument, and the 15-item scale had good convergent and discriminant validity. The three dimensions were named Hedonism, Eudaimonism, and Otherism. Among them, Otherism is a new dimension, which means “the pursuit of the harmony of the group and achieving happiness by fulfilling their responsibilities in the group”. The revised tool was named the Hedonic, Eudaimonic, and Otheristic Motives for Activities Scale-Chinese (HEOMA-C). The results showed that the HEOMA-C has good reliability and validity. Overall, the present study provided an effective tool to assess the OTH in Chinese culture.
Mechanical Model and Damping Effect of a Particle-Inertial Damper
Authors: Xie Mengfei , Xu Weibing , Wang Jin , Chen Yanjiang , Zhou Daxing , Hou Liqun , Sun Yulong , Li Yong
Published: September 2023

Particle dampers (PD) are safe, economical, and effective energy-dissipation devices for structures. However, the additional mass of PD must be sufficiently large to provide a better damping effect, and the initial movement condition of particles has a significant impact on the damping effect of PD. In this study, a particle-inertial damper (PID) is proposed to overcome these problems, and its mechanical model is established with and without considering particle collision. Subsequently, the influence of particle rolling friction and particle collision on the inertial amplification capacity as well as the dynamic response of a single degree of freedom (SDOF) structure with non-collision and collision PID (SDOF-PID) are systematically analysed. Finally, the control effects of a PID and a tuned mass damper (TMD) are compared based on two typical optimisation methods. The results indicate that particle rolling friction has little influence on the inertia amplification effect of a PID and the displacement response of a SDOF-PID. Under harmonic excitation, particle collision significantly affects the damping mechanism of a PID by its equivalent inertia coefficient, equivalent damping coefficient, and equivalent stiffness coefficient. The fixed-point theory and ‘performance-cost’ theory can be used to optimise the PID to a certain extent. The damping effect of a PID on the SDOF under the most severe seismic excitation is better than that of the PID under white noise excitation. With respect to the decreasing ratio of 40~50%, the additional mass of the PID is only one thousandth that of the TMD under the same damping capacity demand.
Prognostic Factors in Patients with Metastatic Spinal Cord Compression Secondary to Lung Cancer—A Retrospective UK Single-Centre Study
Authors: Vassiliou Anna , Osunronbi Temidayo , Enyioma Synthia , Rago Gerardo , Karathanasi Afroditi , Ghose Aruni , Sheriff Matin , Mikropoulos Christos , Sanchez Elisabet , Moschetta Michele , Chargari Cyrus , Rassy Elie , Boussios Stergios
Published: September 2023

Purpose: Metastatic spinal cord compression (MSCC) is a severe complication of cancer that can lead to irreversible neurological impairment, necessitating prompt recognition and intervention. This retrospective, single-centre study aimed to determine the prognostic factors and survival rates among patients presenting with MSCC secondary to lung cancer. Methods and Materials: We identified 74 patients with epidural metastases-related spinal cord compression and a history of lung cancer through the electronic database of Medway Maritime Hospital in the United Kingdom (UK), spanning the period from April 2016 to September 2021. Among them, 39 were below 55 years old, while 35 were aged 55 years or older; 24 patients were diagnosed with small cell lung cancer (SCLC), and 50 patients had non-small cell lung cancer (NSCLC). Results: The median overall survival (OS) was 5.5 months, with 52 out of 74 patients dying within 6 months of diagnosis with MSCC. For the entire cohort, the statistically significant variables on multi-variate analysis were cancer type (NSCLC had improved OS), the number of involved vertebrae (one to two vertebrae involvement had improved OS), and the time taken to develop motor deficits (≤10 days to develop motor deficits had worsened OS). For the NSCLC cohort, the statistically significant variables on multivariate analysis were molecular alterations (patients with epidermal growth factor receptor (EGFR) mutation), pre-treatment ambulatory status, Eastern Cooperative Oncology Group (ECOG) performance status, and the time taken to develop motor deficits. Conclusions: Within the entire cohort, patients diagnosed with NSCLC and spinal metastases affecting one to two vertebrae exhibited enhanced OS. Within the NSCLC subgroup, those with EGFR mutations who were ambulatory and possessed an ECOG performance status of 1–2 demonstrated improved OS. In both the entire cohort and the NSCLC subgroup, the development of motor deficits within a period of ≤10 days was associated with poor OS.
F-box DNA Helicase 1 (FBH1) Contributes to the Destabilization of DNA Damage Repair Machinery in Human Cancers
Authors: Watson Alizhah J. , Shaffer Michaela L. , Bouley Renee A. , Petreaca Ruben C.
Published: September 2023

Homologous recombination (HR) is the major mechanism of rescue of stalled replication forks or repair of DNA double-strand breaks (DSBs) during S phase or mitosis. In human cells, HR is facilitated by the BRCA2-BRCA1-PALB2 module, which loads the RAD51 recombinase onto a resected single-stranded DNA end to initiate repair. Although the process is essential for error-free repair, unrestrained HR can cause chromosomal rearrangements and genome instability. F-box DNA Helicase 1 (FBH1) antagonizes the role of BRCA2-BRCA1-PALB2 to restrict hyper-recombination and prevent genome instability. Here, we analyzed reported FBH1 mutations in cancer cells using the Catalogue of Somatic Mutations in Cancers (COSMIC) to understand how they interact with the BRCA2-BRCA1-PALB2. Consistent with previous results from yeast, we find that FBH1 mutations co-occur with BRCA2 mutations and to some degree BRCA1 and PALB2. We also describe some co-occurring mutations with RAD52, the accessory RAD51 loader and facilitator of single-strand annealing, which is independent of RAD51. In silico modeling was used to investigate the role of key FBH1 mutations on protein function, and a Q650K mutation was found to destabilize the protein structure. Taken together, this work highlights how mutations in several DNA damage repair genes contribute to cellular transformation and immortalization.
PLAC8-Mediated Activation of NOX4 Signalling Restores Angiogenic Function of Endothelial Colony-Forming Cells in Experimental Hypoxia
Authors: Pun Shun Hay , O’Neill Karla M. , Edgar Kevin S. , Gill Eleanor K. , Moez Arya , Naderi-Meshkin Hojjat , Malla Sudhir B. , Hookham Michelle B. , Alsaggaf Mohammed , Madishetti Vinuthna Vani , Botezatu Bianca , King William , Brunssen Coy , Morawietz Henning , Dunne Philip D. , Brazil Derek P. , Medina Reinhold J. , Watson Chris J. , Grieve David J.
Published: September 2023

Ischaemic cardiovascular disease is associated with tissue hypoxia as a significant determinant of angiogenic dysfunction and adverse remodelling. While cord blood-derived endothelial colony-forming cells (CB-ECFCs) hold clear therapeutic potential due to their enhanced angiogenic and proliferative capacity, their impaired functionality within the disease microenvironment represents a major barrier to clinical translation. The aim of this study was to define the specific contribution of NOX4 NADPH oxidase, which we previously reported as a key CB-ECFC regulator, to hypoxia-induced dysfunction and its potential as a therapeutic target. CB-ECFCs exposed to experimental hypoxia demonstrated downregulation of NOX4-mediated reactive oxygen species (ROS) signalling linked with a reduced tube formation, which was partially restored by NOX4 plasmid overexpression. siRNA knockdown of placenta-specific 8 (PLAC8), identified by microarray analysis as an upstream regulator of NOX4 in hypoxic versus normoxic CB-ECFCs, enhanced tube formation, NOX4 expression and hydrogen peroxide generation, and induced several key transcription factors associated with downstream Nrf2 signalling. Taken together, these findings indicated that activation of the PLAC8–NOX4 signalling axis improved CB-ECFC angiogenic functions in experimental hypoxia, highlighting this pathway as a potential target for protecting therapeutic cells against the ischaemic cardiovascular disease microenvironment.
Rat Plantar Fascia Stem/Progenitor Cells Showed Lower Expression of Ligament Markers and Higher Pro-Inflammatory Cytokines after Intensive Mechanical Loading or Interleukin-1β Treatment In Vitro
Authors: Siu Wing Sum , Ma Hui , Ko Chun Hay , Shiu Hoi Ting , Cheng Wen , Lee Yuk Wa , Kot Cheuk Hin , Leung Ping Chung , Lui Pauline Po Yee
Published: September 2023

The pathogenesis of plantar fasciitis is unclear, which hampers the development of an effective treatment. The altered fate of plantar fascia stem/progenitor cells (PFSCs) under overuse-induced inflammation might contribute to the pathogenesis. This study aimed to isolate rat PFSCs and compared their stem cell-related properties with bone marrow stromal cells (BMSCs). The effects of inflammation and intensive mechanical loading on PFSCs’ functions were also examined. We showed that plantar fascia-derived cells (PFCs) expressed common MSC surface markers and embryonic stemness markers. They expressed lower Nanog but higher Oct4 and Sox2, proliferated faster and formed more colonies compared to BMSCs. Although PFCs showed higher chondrogenic differentiation potential, they showed low osteogenic and adipogenic differentiation potential upon induction compared to BMSCs. The expression of ligament markers was higher in PFCs than in BMSCs. The isolated PFCs were hence PFSCs. Both IL-1β and intensive mechanical loading suppressed the mRNA expression of ligament markers but increased the expression of inflammatory cytokines and matrix-degrading enzymes in PFSCs. In summary, rat PFSCs were successfully isolated. They had poor multi-lineage differentiation potential compared to BMSCs. Inflammation after overuse altered the fate and inflammatory status of PFSCs, which might lead to poor ligament differentiation of PFSCs and extracellular matrix degeneration. Rat PFSCs can be used as an in vitro model for studying the effects of intensive mechanical loading-induced inflammation on matrix degeneration and erroneous stem/progenitor cell differentiation in plantar fasciitis.
Developmental Exposure to Kynurenine Affects Zebrafish and Rat Behavior
Authors: Marszalek-Grabska Marta , Gawel Kinga , Kosheva Nataliia , Kocki Tomasz , Turski Waldemar A.
Published: September 2023

Proper nutrition and supplementation during pregnancy and breastfeeding are crucial for the development of offspring. Kynurenine (KYN) is the central metabolite of the kynurenine pathway and a direct precursor of other metabolites that possess immunoprotective or neuroactive properties, with the ultimate effect on fetal neurodevelopment. To date, no studies have evaluated the effects of KYN on early embryonic development. Thus, the aim of our study was to determine the effect of incubation of larvae with KYN in different developmental periods on the behavior of 5-day-old zebrafish. Additionally, the effects exerted by KYN administered on embryonic days 1–7 (ED 1–7) on the behavior of adult offspring of rats were elucidated. Our study revealed that the incubation with KYN induced changes in zebrafish behavior, especially when zebrafish embryos or larvae were incubated with KYN from 1 to 72 h post-fertilization (hpf) and from 49 to 72 hpf. KYN administered early during pregnancy induced subtle differences in the neurobehavioral development of adult offspring. Further research is required to understand the mechanism of these changes. The larval zebrafish model can be useful for studying disturbances in early brain development processes and their late behavioral consequences. The zebrafish-medium system may be applicable in monitoring drug metabolism in zebrafish.