bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of age and cognitive demand on motor decision making under uncertainty: a study on goal directed reaching movements
Authors: Krüger Melanie , Puri Rohan , Summers Jeffery J. , Hinder Mark R.
Published: April 2024

In everyday life, we constantly make decisions about actions to be performed subsequently. Research on motor decision making has provided empirical evidence for an influence of decision uncertainty on movement execution in young adults. Further, decision uncertainty was suggested to be increased in older adults due to limited cognitive resources for the integration of information and the prediction of the decision outcomes. However, the influence of cognitive aging on decision uncertainty during motor decision making and movement execution has not been investigated, yet. Thus, in the current study, we presented young and older adults with a motor decision making task, in which participants had to decide on pointing towards one out of five potential targets under varying cognitive demands. Statistical analyses revealed stronger decreases in correctly deciding upon the pointing target, i.e. task performance, from low to higher cognitive demand in older as compared to young adults. Decision confidence also decreased more strongly in older adults with increasing cognitive demand, however, only when collapsing across correct and incorrect decision trials, but not when considering correct decision trials, only. Further, older adults executed reaching movements with longer reaction times and increased path length, though the latter, again, not when considering correct decision trials, only. Last, reaction time and variability in movement execution were both affected by cognitive demand. The outcomes of this study provide a differentiated picture of the distinct and joint effects of aging and cognitive demand during motor decision making.
Interleukin-1α links peripheral CaV2.2 channel activation to rapid adaptive increases in heat sensitivity in skin
Authors: Salib Anne-Mary N. , Crane Meredith J. , Lee Sang Hun , Wainger Brian J. , Jamieson Amanda M. , Lipscombe Diane
Published: April 2024

Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated CaV2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1α (IL-1α), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1α was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1α levels were also dependent on peripheral CaV2.2 channel activity. Neutralizing IL-1α in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1α enhances behavioral responses to stimuli and, in culture, IL-1α enhances the responsiveness of Trpv1-expressing sensory neurons. Together, our data suggest that IL-1α is the key cytokine that underlies rapid and reversible neuroinflammatory responses in skin.
Optimizing vitiligo diagnosis with ResNet and Swin transformer deep learning models: a study on performance and interpretability
Authors: Zhong Fan , He Kaiqiao , Ji Mengqi , Chen Jianru , Gao Tianwen , Li Shuli , Zhang Junpeng , Li Chunying
Published: April 2024

Vitiligo is a hypopigmented skin disease characterized by the loss of melanin. The progressive nature and widespread incidence of vitiligo necessitate timely and accurate detection. Usually, a single diagnostic test often falls short of providing definitive confirmation of the condition, necessitating the assessment by dermatologists who specialize in vitiligo. However, the current scarcity of such specialized medical professionals presents a significant challenge. To mitigate this issue and enhance diagnostic accuracy, it is essential to build deep learning models that can support and expedite the detection process. This study endeavors to establish a deep learning framework to enhance the diagnostic accuracy of vitiligo. To this end, a comparative analysis of five models including ResNet (ResNet34, ResNet50, and ResNet101 models) and Swin Transformer series (Swin Transformer Base, and Swin Transformer Large models), were conducted under the uniform condition to identify the model with superior classification capabilities. Moreover, the study sought to augment the interpretability of these models by selecting one that not only provides accurate diagnostic outcomes but also offers visual cues highlighting the regions pertinent to vitiligo. The empirical findings reveal that the Swin Transformer Large model achieved the best performance in classification, whose AUC, accuracy, sensitivity, and specificity are 0.94, 93.82%, 94.02%, and 93.5%, respectively. In terms of interpretability, the highlighted regions in the class activation map correspond to the lesion regions of the vitiligo images, which shows that it effectively indicates the specific category regions associated with the decision-making of dermatological diagnosis. Additionally, the visualization of feature maps generated in the middle layer of the deep learning model provides insights into the internal mechanisms of the model, which is valuable for improving the interpretability of the model, tuning performance, and enhancing clinical applicability. The outcomes of this study underscore the significant potential of deep learning models to revolutionize medical diagnosis by improving diagnostic accuracy and operational efficiency. The research highlights the necessity for ongoing exploration in this domain to fully leverage the capabilities of deep learning technologies in medical diagnostics.
NET-related gene signature for predicting AML prognosis
Authors: Wang Jiajia , Wang Huiping , Ding Yangyang , Jiao Xunyi , Zhu Jinli , Zhai Zhimin
Published: April 2024

Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS). The least absolute shrinkage and selection operator were utilized to assess the predictive efficacy of NRGs. Kaplan–Meier plots visualized survival estimates. ROC curves assessed the prognostic value of NRG-based features. A nomogram, integrating clinical information and prognostic scores of patients, was constructed using multivariate logistic regression and Cox proportional hazards regression models. Twenty-seven NRGs were found to significantly impact patient OS. Six NRGs—CFTR, ENO1, PARVB, DDIT4, MPO, LDLR—were notable for their strong predictive ability regarding patient survival. The ROC values for 1-, 3-, and 5-year survival rates were 0.794, 0.781, and 0.911, respectively. In the training set (TCGA-LAML), patients in the high NRG risk group showed a poorer prognosis (p < 0.001), which was validated in two external datasets (GSE71014 and GSE106291). The 6-NRG signature and corresponding nomograms exhibit superior predictive accuracy, offering insights for pre-immune response evaluation and guiding future immuno-oncology treatments and drug selection for AML patients.
Stability of transcranial magnetic stimulation electroencephalogram evoked potentials in pediatric epilepsy
Authors: She Xiwei , Nix Kerry C. , Cline Christopher C. , Qi Wendy , Tugin Sergei , He Zihuai , Baumer Fiona M.
Published: April 2024

Transcranial magnetic stimulation paired with electroencephalography (TMS–EEG) can measure local excitability and functional connectivity. To address trial-to-trial variability, responses to multiple TMS pulses are recorded to obtain an average TMS evoked potential (TEP). Balancing adequate data acquisition to establish stable TEPs with feasible experimental duration is critical when applying TMS–EEG to clinical populations. Here we aim to investigate the minimum number of pulses (MNP) required to achieve stable TEPs in children with epilepsy. Eighteen children with Self-Limited Epilepsy with Centrotemporal Spikes, a common epilepsy arising from the motor cortices, underwent multiple 100-pulse blocks of TMS to both motor cortices over two days. TMS was applied at 120% of resting motor threshold (rMT) up to a maximum of 100% maximum stimulator output. The average of all 100 pulses was used as a “gold-standard” TEP to which we compared “candidate” TEPs obtained by averaging subsets of pulses. We defined TEP stability as the MNP needed to achieve a concordance correlation coefficient of 80% between the candidate and “gold-standard” TEP. We additionally assessed whether experimental or clinical factors affected TEP stability. Results show that stable TEPs can be derived from fewer than 100 pulses, a number typically used for designing TMS-EEG experiments. The early segment (15–80 ms) of the TEP was less stable than the later segment (80–350 ms). Global mean field amplitude derived from all channels was less stable than local TEP derived from channels overlying the stimulated site. TEP stability did not differ depending on stimulated hemisphere, block order, or antiseizure medication use, but was greater in older children. Stimulation administered with an intensity above the rMT yielded more stable local TEPs. Studies of TMS-EEG in pediatrics have been limited by the complexity of experimental set-up and time course. This study serves as a critical starting point, demonstrating the feasibility of designing efficient TMS–EEG studies that use a relatively small number of pulses to study pediatric epilepsy and potentially other pediatric groups.
Identification of metabolism-related key genes as potential biomarkers for pathogenesis of immune thrombocytopenia
Authors: Xu Xiangmei , Zhang Jiamin , Xing Hongyun , Han Liying , Li Xiaoming , Wu Pengqiang , Tang Jirui , Jing Li , Luo Jie , Luo Jing , Liu Lin
Published: April 2024

Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that contributes to disease pathogenesis and reflects disease activity. Metabolic alterations are reported to be associated with the occurrence of various diseases. As metabolic biomarkers for ITP have not been identified. This study aimed to identify metabolism-related differentially expressed genes as potential biomarkers for pathogenesis of ITP using bioinformatic analyses.The microarray expression data of the peripheral blood mononuclear cells were downloaded from the Gene Expression Omnibus database (GSE112278 download link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112278). Key module genes were intersected with metabolism-related genes to obtain the metabolism-related key candidate genes. The hub genes were screened based on the degree function in the coytoscape sofware. The key ITP-related genes were subjected to functional enrichment analysis. Immune infiltration analysis was performed using a single-sample gene set enrichment analysis algorithm to evaluate the differential infiltration levels of immune cell types between ITP patient and control. Molecular subtypes were identified based on the expression of hub genes. The expression of hub genes in the ITP patients was validated using quantitative real-time polymerase chain reaction analysis. This study identified five hub genes (ADH4, CYP7A1, CYP1A2, CYP8B1, and NR1H4), which were be associated with the pathogenesis of ITP, and two molecular subtypes of ITP. Among these hub genes, CYP7A1 and CYP8B1 involved in cholesterol metabolism,were further verified in clinical samples.
Dynamics of CD44+ bovine nucleus pulposus cells with inflammation
Authors: Ferreira J. R. , Caldeira J. , Sousa M. , Barbosa M. A. , Lamghari M. , Almeida-Porada G. , Gonçalves R. M.
Published: April 2024

Intervertebral Disc (IVD) degeneration has been associated with a chronic inflammatory response, but knowledge on the contribution of distinct IVD cells, namely CD44, to the progression of IVD degeneration remains elusive. Here, bovine nucleus pulposus (NP) CD44 cells were sorted and compared by gene expression and proteomics with the negative counterpart. NP cells were then stimulated with IL-1b (10 ng/ml) and dynamics of CD44 gene and protein expression was analyzed upon pro-inflammatory treatment. The results emphasize that CD44 has a multidimensional functional role in IVD metabolism, ECM synthesis and production of neuropermissive factors. CD44 widespread expression in NP was partially associated with CD14 and CD45, resulting in the identification of distinct cell subsets. In conclusion, this study points out CD44 and CD44-based cell subsets as relevant targets in the modulation of the IVD pro-inflammatory/degenerative cascade.
Dynamic equilibrium of skeletal muscle macrophage ontogeny in the diaphragm during homeostasis, injury, and recovery
Authors: Li Qian , Liang Feng , Bhattarai Salyan , Divangahi Maziar , Kaufmann Eva , Petrof Basil J.
Published: April 2024

The diaphragm is a unique skeletal muscle due to its continuous activation pattern during the act of breathing. The ontogeny of macrophages, pivotal cells for skeletal muscle maintenance and regeneration, is primarily based on two distinct origins: postnatal bone marrow-derived monocytes and prenatal embryonic progenitors. Here we employed chimeric mice to study the dynamics of these two macrophage populations under different conditions. Traditional chimeric mice generated through whole body irradiation showed virtually complete elimination of the original tissue-resident macrophage pool. We then developed a novel method which employs lead shielding to protect the diaphragm tissue niche from irradiation. This allowed us to determine that up to almost half of tissue-resident macrophages in the diaphragm can be maintained independently from bone marrow-derived monocytes under steady-state conditions. These findings were confirmed by long-term (5 months) parabiosis experiments. Acute diaphragm injury shifted the macrophage balance toward an overwhelming predominance of bone marrow (monocyte)-derived macrophages. However, there was a remarkable reversion to the pre-injury ontological landscape after diaphragm muscle recovery. This diaphragm shielding method permits analysis of the dynamics of macrophage origin and corresponding function under different physiological and pathological conditions. It may be especially useful for studying diseases which are characterized by acute or chronic injury of the diaphragm and accompanying inflammation.
Serum neurofilament light chain and inflammatory cytokines as biomarkers for early detection of mild cognitive impairment
Authors: Jing Xinyang , Wang Lan , Song Mei , Geng Hao , Li Wei , Huo Yaxin , Huang Anqi , Wang Xueyi , An Cuixia
Published: April 2024

To investigate the association between serum neurofilament light chain (NfL) levels, inflammatory cytokines, and cognitive function to assess their utility in the early detection of mild cognitive impairment (MCI). We conducted a cross-sectional study involving 157 community-dwelling individuals aged 55 years and above, categorized into healthy controls, MCI, and probable Alzheimer's disease (AD). Serum levels of NfL, inflammatory cytokines, and AD pathology markers were measured using enzyme-linked immunosorbent assay (ELISA). Correlations between these biomarkers and cognitive function were analyzed, and the diagnostic performance of the cognitive assessment scales and serum biomarker concentrations was evaluated using receiver operating characteristic (ROC) curve analysis. Serum NfL levels were significantly elevated in MCI and probable AD groups compared to healthy controls. Positive correlations were found between serum NfL and inflammatory cytokines IL-1β, IL-6, and Aβ40. Combining serum NfL with p-tau217 and the Boston Naming Test significantly enhanced the predictive accuracy for MCI. However, combining serum NfL with inflammatory markers did not improve MCI prediction accuracy. Elevated serum NfL is associated with cognitive impairment and inflammatory markers, suggesting its potential as a peripheral serum biomarker for MCI detection. The combination of serum NfL with p-tau217 and cognitive tests could offer a more accurate prediction of MCI, providing new insights for AD treatment strategies.
L-NAC and L-NAC methyl ester prevent and overcome physical dependence to fentanyl in male rats
Authors: Bates James N. , Baby Santhosh M. , Getsy Paulina M. , Coffee Gregory A. , Hsieh Yee-Hsee , Knauss Zackery T. , Dahan Albert , Bubier Jason A. , MacFarlane Peter M. , Mueller Devin , Lewis Stephen J.
Published: April 2024

N-acetyl-L-cysteine (L-NAC) is a proposed therapeutic for opioid use disorder. This study determined whether co-injections of L-NAC (500 μmol/kg, IV) or its highly cell-penetrant analogue, L-NAC methyl ester (L-NACme, 500 μmol/kg, IV), prevent acquisition of acute physical dependence induced by twice-daily injections of fentanyl (125 μg/kg, IV), and overcome acquired dependence to these injections in freely-moving male Sprague Dawley rats. The injection of the opioid receptor antagonist, naloxone HCl (NLX; 1.5 mg/kg, IV), elicited a series of withdrawal phenomena (i.e. behavioral and cardiorespiratory responses, hypothermia and body weight loss) in rats that received 5 or 10 injections of fentanyl and similar numbers of vehicle co-injections. With respect to the development of dependence, the NLX-precipitated withdrawal phenomena were reduced in rats that received had co-injections of L-NAC, and more greatly reduced in rats that received co-injections of L-NACme. In regard to overcoming established dependence, the NLX-precipitated withdrawal phenomena in rats that had received 10 injections of fentanyl (125 μg/kg, IV) were reduced in rats that had received co-injections of L-NAC, and more greatly reduced in rats that received co-injections of L-NACme beginning with injection 6 of fentanyl. This study provides compelling evidence that co-injections of L-NAC and L-NACme prevent the acquisition of physical dependence and overcome acquired dependence to fentanyl in male rats. The higher efficacy of L-NACme is likely due to its greater cell penetrability in brain regions mediating dependence to fentanyl and interaction with intracellular signaling cascades, including redox-dependent processes, responsible for the acquisition of physical dependence to fentanyl.
A high-precision wound healing assay based on photosensitized culture substrates
Authors: Azzam Saphia , Tomasova Lea , Danner Carina , Skiba Michael , Klein Maren , Guttenberg Zeno , Michaelis Stefanie , Wegener Joachim
Published: April 2024

Quantitative assessment of cell migration in vitro is often required in fundamental and applied research from different biomedical areas including wound repair, tumor metastasis or developmental biology. A collection of assays has been established throughout the years like the most widely used scratch assay or the so-called barrier assay. It is the principle of these assays to introduce a lesion into an otherwise confluent monolayer in order to study the migration of cells from the periphery into this artificial wound and determine the migration rate from the time necessary for wound closure. A novel assay makes use of photosensitizers doped into a polystyrene matrix. A thin layer of this composite material is coated on the bottom of regular cell culture ware showing perfect biocompatibility. When adherent cells are grown on this coating, resonant excitation of the photosensitizer induces a very local generation of 1O2, which kills the cells residing at the site of illumination. Cells outside the site of illumination are not harmed. When excitation of the photosensitizer is conducted by microscopic illumination, high-precision wounding in any size and geometry is available even in microfluidic channels. Besides proof-of-concept experiments, this study gives further insight into the mechanism of photosensitizer-mediated cell wounding.
Geochemical characteristics, hazards impact assessment and radiogenic heat production of the alkaline rocks
Authors: Sidique Essam , Elhaddad Mervat A. , Sami Mabrouk , Sanislav Ioan V. , Alshehri Fahad , Ahmed Mohamed S. , Abbas Hassan
Published: April 2024

This study primarily investigates the natural radioactivity level in alkaline rocks collected from the Wadi El-Dib ring complex (WDRC) in North Eastern Desert of Egypt, and assesses potential health risks associated with their use as decorative building materials. The work was accomplished using a high-purity germanium detector as well as ICP-MS and ICP-AES techniques. The WDRC composed essentially of trachyte, quartz syenite, granite and syenite. Geochemically, these rocks contain high SiO2 and alkalis with metaluminous to slightly peraluminous features. All rocks contain high concentrations of rare earth elements (∑REEs = 109–1075 ppm), with clear enrichment in light REEs compared to heavy REEs [(La/Yb)N = 8.3–25.3. Radiometrically, the concentrations of the natural radioisotopes (238U, 232Th, and 40K) in the studied rock types surpassed the worldwide average values assigned for building materials by UNSCEAR. This elevation of the radioisotope concentration values is due to the presence of supplement minerals such as monazite, zircon, allanite, and rutile. Granites exhibit the highest mean concentrations of 238U (av. 164.24 ± 14.76 Bq/kg) and 232Th (av. 214.37 ± 23.33 Bq/kg), while trachytes demonstrate the highest 40K (av. 1352.56 ± 65.56 Bq/kg) concentrations. In contrast, syenites exhibite the lowest mean concentrations for 238U (av. 54.51 ± 6.81 Bq/kg) and 232Th (av. 56.76 ± 6.25 Bq/kg), while quartz syenites display the lowest mean concentration of 40K (av. 1144.78 ± 96.19 Bq/kg). The radiogenic heat production (RHP) associated with U, Th, and K range between 1.41 to 9.33 μW/m3, exceeding the typical crustal mean value of 0.8 to 1.2 μW/m3. The radiological parameters and indices evaluating risks of the outdoor and indoor radiation doses due to the investigated rocks were assessed. The results indicated that these rocks meet globally accepted values and safety standards (approved by UNSCEAR, ICRP, and EC) for surface building materials, as well as they underscore the importance of adhering to safety protocols to safeguard workers from radiation exposure within the WDRC area. Ultimately, the data herein provide a valuable database for assessing the compatibility of geochemical data and natural radioactivity level in WDRC rocks. Additionally, it reveals that from the radiological perspective, the investigated rocks are considered safe for use as decorative construction materials.
Longitudinal vibration control of a double-rod system by employing nonlinear energy sinks
Authors: Zhao Yuhao , Li Zheng , Cui Haijian , Xu Deshui
Published: April 2024

This study aims to potential the potential utilization of nonlinear energy sinks (NESs) for controlling longitudinal vibrations in a double-rod system. The research introduces a longitudinal vibration prediction model for a double-rod system equipped with NESs. The generalized Hamilton principle is employed to derive governing equations of the double-rod system. The longitudinal vibration responses of the double-rod system are numerically solved through the application of Galerkin truncation method. The longitudinal vibration responses of the double-rod system are impacted by NESs, as they yield accurate numerical results. The installation of both NES 1 and NES 2 concurrently is recommended for mitigating the vibration of the double-rod system. Under reasonable single-frequency excitations, modifying the parameters of NESs can significantly alter both the vibration state and magnitudes of vibration in the double-rod system. Furthermore, the synchronous optimization of parameters in NES 1 and NES 2 is crucial for effectively controlling vibrations in the double-rod system. Sensitive parameter areas of NESs provide the possibility of controlling the vibration of the double-rod system by utilizing NESs.
The overlooked evolutionary dynamics of 16S rRNA revises its role as the “gold standard” for bacterial species identification
Authors: Bartoš Oldřich , Chmel Martin , Swierczková Iva
Published: April 2024

The role of 16S rRNA has been and largely remains crucial for the identification of microbial organisms. Although 16S rRNA could certainly be described as one of the most studied sequences ever, the current view of it remains somewhat ambiguous. While some consider 16S rRNA to be a variable marker with resolution power down to the strain level, others consider them to be living fossils that carry information about the origin of domains of cellular life. We show that 16S rRNA is clearly an evolutionarily very rigid sequence, making it a largely unique and irreplaceable marker, but its applicability beyond the genus level is highly limited. Interestingly, it seems that the evolutionary rigidity is not driven by functional constraints of the sequence (RNA–protein interactions), but rather results from the characteristics of the host organism. Our results suggest that, at least in some lineages, Horizontal Gene Transfer (HGT) within genera plays an important role for the evolutionary non-dynamics (stasis) of 16S rRNA. Such genera exhibit an apparent lack of diversification at the 16S rRNA level in comparison to the rest of a genome. However, why it is limited specifically and solely to 16S rRNA remains enigmatic.
Increased prevalence but decreased survival of nonviral hepatocellular carcinoma compared to viral hepatocellular carcinoma in recent ten years
Authors: Chen Ting-Chun , Hsiao Shun-Wen , Chen Yang-Yuan , Yen Hsu-Heng , Su Wei-Wen , Hsu Yu-Chun , Huang Siou-Ping , Su Pei-Yuan
Published: April 2024

Due to the comprehensive hepatitis B virus vaccination program in Taiwan since 1986, the development of antiviral therapy for chronic hepatitis B and chronic hepatitis C infection and covered by National health insurance. Besides, the increased prevalence of nonalcoholic fatty liver disease (NAFLD) and currently, approved therapy for NAFLD remain developing. The etiology of liver-related diseases such as cirrhosis and hepatocellular carcinoma required reinterpretation. This study aimed to analyze the incidence and outcome of hepatocellular carcinoma (HCC) due to viral (hepatitis B and hepatitis C) infection compared to that of nonviral etiology. We retrospectively analyzed patients with HCC from January 2011 to December 2020 from the cancer registry at our institution. Viral-related hepatitis was defined as hepatitis B surface antigen positivity or anti-hepatitis C virus (HCV) antibody positivity. A total of 2748 patients with HCC were enrolled, of which 2188 had viral-related HCC and 560 had nonviral-related HCC. In viral HCC group, the median age at diagnosis was significantly lower (65 years versus 71 years, p < 0.001), and the prevalence of early-stage HCC, including stage 0 and stage A Barcelona Clinic Liver Cancer, was significantly higher (52.9% versus 33.6%, p < 0.001). In nonviral HCC group, alcohol use was more common (39.9% versus 30.1%, p < 0.001), the prevalence of type 2 diabetes mellitus (T2DM) was higher (54.5% versus 35.1%, p < 0.001), and obesity was common (25.0% versus 20.5%, p = 0.026). The prevalence of nonviral HCC increased significantly from 19.2 to 19.3% and 23.0% in the last 10 years (p = 0.046). Overall survival was better in the viral HCC group (5.95 years versus 4.00 years, p < 0.001). In the early stage of HCC, overall survival was still better in the viral HCC group (p < 0.001). The prevalence of nonviral HCC has significantly increased in the last ten years. The overall survival was significantly lower in the nonviral HCC, perhaps because the rate of early HCC detection is lower in nonviral HCC and anti-viral therapy. To detect nonviral HCC early, we should evaluate liver fibrosis in high-risk groups (including people with obesity or T2DM with NAFLD/NASH and alcoholic liver disease) and regular follow-up for those with liver fibrosis, regardless of cirrhosis.
Optimization of plasma-based BioID identifies plasminogen as a ligand of ADAMTS13
Authors: Madarati Hasam , DeYoung Veronica , Singh Kanwal , Sparring Taylor , Kwong Andrew C. , Fredenburgh James C. , Teney Cherie , Koschinsky Marlys L. , Boffa Michael B. , Weitz Jeffrey I. , Kretz Colin A.
Published: April 2024

ADAMTS13, a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13, regulates the length of Von Willebrand factor (VWF) multimers and their platelet-binding activity. ADAMTS13 is constitutively secreted as an active protease and is not inhibited by circulating protease inhibitors. Therefore, the mechanisms that regulate ADAMTS13 protease activity are unknown. We performed an unbiased proteomics screen to identify ligands of ADAMTS13 by optimizing the application of BioID to plasma. Plasma BioID identified 5 plasma proteins significantly labeled by the ADAMTS13-birA* fusion, including VWF and plasminogen. Glu-plasminogen, Lys-plasminogen, mini-plasminogen, and apo(a) bound ADAMTS13 with high affinity, whereas micro-plasminogen did not. None of the plasminogen variants or apo(a) bound to a C-terminal truncation variant of ADAMTS13 (MDTCS). The binding of plasminogen to ADAMTS13 was attenuated by tranexamic acid or ε-aminocaproic acid, and tranexamic acid protected ADAMTS13 from plasmin degradation. These data demonstrate that plasminogen is an important ligand of ADAMTS13 in plasma by binding to the C-terminus of ADAMTS13. Plasmin proteolytically degrades ADAMTS13 in a lysine-dependent manner, which may contribute to its regulation. Adapting BioID to identify protein-interaction networks in plasma provides a powerful new tool to study protease regulation in the cardiovascular system.
Hemoglobin levels are associated with retinal vascular caliber in a middle-aged birth cohort
Authors: Sakko Samuli , Karpale Mikko , Tapio Joona , Leppänen Iina , Ahokas Oona , Saarela Ville , Liinamaa M. Johanna , Koivunen Peppi
Published: April 2024

Vascular and neural structures of the retina can be visualized non-invasively and used to predict ocular and systemic pathologies. We set out to evaluate the association of hemoglobin (Hb) levels within the national reference interval with retinal vascular caliber, optical coherence tomography (OCT) and visual field (VF) parameters in the Northern Finland 1966 Birth Cohort (n = 2319, 42.1% male, average age 47 years). The studied parameters were evaluated in Hb quintiles and multivariable linear regression models. The lowest Hb quintile of both sexes presented the narrowest central retinal vein equivalent (CRVE) and the healthiest cardiometabolic profile compared to the other Hb quintiles. In the regression models, CRVE associated positively with Hb levels in both sexes, (Bmales = 0.068 [0.001; 0.135], Bfemales = 0.087 [0.033; 0.140]), after being adjusted for key cardiometabolic and inflammatory parameters, smoking status, and fellow vessel caliber. No statistically significant associations of Hb levels with central retinal artery equivalent, OCT or VF parameters were detected. In conclusion, Hb levels were positively and specifically associated with CRVE, indicating that Hb levels are an independent factor affecting CRVE and the effect is in parallel with established risk factors for cardiometabolic diseases.
Photoresponse of new azo pyridine functionalized poly(2-hydroxyethyl methacrylate-co-methyl methacrylate)
Authors: Konieczkowska Jolanta , Neugebauer Dorota , Kozanecka-Szmigiel Anna , Mazur Aleksy , Kotowicz Sonia , Schab-Balcerzak Ewa
Published: April 2024

A new azo polymer containing photoisomerizable azo pyridine functionalities was synthesized via Mitsunobu reaction of 4-(4-hydroxyphenylazo)pyridine with poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) for creating new photochromic materials. The resulting polymer with azo pyridine side groups was characterized for structural, thermal, and optical properties. UV–vis, 1H NMR and IR spectroscopies confirmed that all hydroxyl groups in p(HEMA-co-MMA) were substituted with azo dye. The obtained azo copolymer exhibited high thermal stability (around 240 °C) and a glass transition temperature (113 °C), promising for applications. The trans-to-cis isomerization upon UV irradiation and the thermal back reaction of the azo chromophore in the copolymer in the solid state was studied. A photostationary state with 50% content of cis-isomers upon 6 min of UV irradiation was reached, and during 48 h dark relaxation at ambient temperature, all cis-isomers converted to the trans form. Additionally, the possibility of efficient photogeneration of surface relief gratings with high amplitude of azo copolymer surface modulation was demonstrated.
Mechanism study of tyrosine phosphatase shp-1 in inhibiting hepatocellular carcinoma progression by regulating the SHP2/GM-CSF pathway in TAMs
Authors: Wei Qiang , Luo ShuBin , He Gang
Published: April 2024

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Macrophage-mediated innate immune responses play a crucial role in tumor development. This study revealed the mechanism of SHP-1 in regulating HCC progression. SHP-1 inhibits tumour development in vivo. Increasing SHP-1 expression in macrophages promotes the expression of p-SHP-1, SHP2, and p-SHP-2. In macrophages GM-CSF recruits SHP-2 to the GM-CSF receptor GM-CSFR induces p-SHP-2 dephosphorylation. GM-CSF recruits p-SHP-2 for dephosphorylation by up-regulating HoxA10HOXA10 activates the transcription of TGFβ2 by interacting with tandem cis-elements in the promoter thereby regulating the proliferation and migration of liver cancer cells. GM-CSF inhibits SHP-1 regulation of p-SHP-1, SHP2, and p-SHP-2 in macrophages. Detailed studies have shown that SHP-1 regulates SHP2 expression, and SHP-1 and SHP2 are involved in macrophage M2 polarisation. SHP-1 inhibits HOXA10 and TGFβ2 which in turn regulates the expression of the migration-associated proteins, MMP2/9, and the migration of hepatocellular carcinoma cells. Overexpression of SHP-1 inhibits macrophage M2 polarisation via the p-STAT3/6 signalling pathway Classical markers arginase-1, CD206, CD163 and regulate the expression of M2 polarisation cytokines IL-4 and IL-10. In addition, hypoxia-induced ROS inhibited SHP-1 regulation by suppressing the expression of p-SHP-1. The combined effect of GM-CSF and ROS significantly increased p-HOXA10/TGFβ2 and macrophage M2 polarisation, and the regulatory effect of ROS was significantly suppressed by GM-CSF knockdown. These findings suggest that increasing the expression of tyrosine phosphatase SHP-1 can inhibit hepatocellular carcinoma progression by modulating the SHP2/GM-CSF pathway in TAM and thus inhibit the progression of hepatocellular carcinoma.
Temporal meta-optimiser based sensitivity analysis (TMSA) for agent-based models and applications in children’s services
Authors: White Luke , Basurra Shadi , Alsewari Abdulrahman A. , Saeed Faisal , Addanki Sudhamshu Mohan
Published: April 2024

With current and predicted economic pressures within English Children’s Services in the UK, there is a growing discourse around the development of methods of analysis using existing data to make more effective interventions and policy decisions. Agent-Based modelling shows promise in aiding in this, with limitations that require novel methods to overcome. This can include challenges in managing model complexity, transparency, and validation; which may deter analysts from implementing such Agent-Based simulations. Children’s Services specifically can gain from the expansion of modelling techniques available to them. Sensitivity analysis is a common step when analysing models that currently has methods with limitations regarding Agent-Based Models. This paper outlines an improved method of conducting Sensitivity Analysis to enable better utilisation of Agent-Based models (ABMs) within Children’s Services. By using machine learning based regression in conjunction with the Nomadic Peoples Optimiser (NPO) a method of conducting sensitivity analysis tailored for ABMs is achieved. This paper demonstrates the effectiveness of the approach by drawing comparisons with common existing methods of sensitivity analysis, followed by a demonstration of an improved ABM design in the target use case.
The influence of environmental factors on the job burnout of physical education teachers in tertiary education
Authors: Li KunZhan , Xu XiaoShu , Zhang YunFeng , Xu XinYu
Published: April 2024

This study takes environmental factors and individual factors as variables to explore the deep internal mechanism of the impact of a comprehensive environment on higher education physical education (PE) teachers’ job burnout. Little research has been done on how environmental factors affect the internal mechanism of college and university PE teachers’ job burnout through individual factors (e.g., professional pressure and teaching efficacy). In this study, the participants were 231 PE teachers from seven comprehensive universities, and four questionnaires were administered to measure the participants’ job burnout, perceived overall environment, teaching efficacy, and occupational stress. Research has found that environmental factors have a significant negative impact on occupational stress, and occupational stress plays an important mediating role between environment and occupational burnout. Research has shown that differences in external environments lead to varying levels of personal stress among college physical education teachers, which in turn affects their level of occupational burnout. The study concludes that a good social, working, and living environment helps to reduce the work pressure on PE teachers, improves their sense of teaching efficacy, and inhibits the occurrence of teachers’ job burnout.
Water adsorption on surfaces of calcium aluminosilicate crystal phase of stone wool: a DFT study
Authors: Ho Thi H. , Hoang Nguyen-Hieu , Wilhelmsen Øivind , Trinh Thuat T.
Published: April 2024

Stone wool is widely used as an efficient thermal insulator within the construction industry; however, its performance can be significantly impacted by the presence of water vapor. By altering the material’s characteristics and effective thermo-physical properties, water vapor can reduce overall efficacy in various environmental conditions. Therefore, understanding water adsorption on stone wool surfaces is crucial for optimizing insulation properties. Through the investigation of interaction between water molecules and calcium aluminosilicate (CAS) phase surfaces within stone wool using density functional theory (DFT), we can gain insight into underlying mechanisms governing water adsorption in these materials. This research aims to elucidate the molecular-level interaction between water molecules and CAS surfaces, which is essential for understanding fundamental properties that govern their adsorption process. Both dissociative and molecular adsorptions were investigated in this study. For molecular adsorption, the adsorption energy ranged from $$-$$
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 84 to $$-$$
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 113 kJ mol$$^{-1}$$

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1

depending on surface orientation. A wider range of adsorption energy ($$-$$
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 132 to $$-$$
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 236 kJ mol$$^{-1}$$

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1

) was observed for dissociative adsorption. Molecular adsorption was energetically favored on (010) surfaces while dissociative adsorption was most favorable on (111) surfaces. This DFT study provides valuable insights into the water adsorption behavior on low index surfaces of CAS phase in stone wool, which can be useful for designing effective strategies to manage moisture-related issues in construction materials. Based on these findings, additional research on the dynamics and kinetics of water adsorption and desorption processes of this thermal isolation material is suggested.
Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation
Authors: Feng Fang , Ko Hyun-A , Truong Thi My Tien , Song Woo-Jin , Ko Eun-Ju , Kang Inhae
Published: April 2024

Brown adipose tissue (BAT) which is a critical regulator of energy homeostasis, and its activity is inhibited by obesity and low-grade chronic inflammation. Ginsenoside Rg3, the primary constituent of Korean red ginseng (steamed Panax ginseng CA Meyer), has shown therapeutic potential in combating inflammatory and metabolic diseases. However, it remains unclear whether Rg3 can protect against the suppression of browning or activation of BAT induced by inflammation. In this study, we conducted a screening of ginsenoside composition in red ginseng extract (RGE) and explored the anti-adipogenic effects of both RGE and Rg3. We observed that RGE (exist 0.25 mg/mL of Rg3) exhibited significant lipid-lowering effects in adipocytes during adipogenesis. Moreover, treatment with Rg3 (60 μM) led to the inhibition of triglyceride accumulation, subsequently promoting enhanced fatty acid oxidation, as evidenced by the conversion of radiolabeled 3H-fatty acids into 3H-H2O with mitochondrial activation. Rg3 alleviated the attenuation of browning in lipopolysaccharide (LPS)-treated beige adipocytes and primary brown adipocytes by recovered by uncoupling protein 1 (UCP1) and the oxygen consumption rate compared to the LPS-treated group. These protective effects of Rg3 on inflammation-induced inhibition of beige and BAT-derived thermogenesis were confirmed in vivo by treating with CL316,243 (a beta-adrenergic receptor agonist) and LPS to induce browning and inflammation, respectively. Consistent with the in vitro data, treatment with Rg3 (2.5 mg/kg, 8 weeks) effectively reversed the LPS-induced inhibition of brown adipocyte features in C57BL/6 mice. Our findings confirm that Rg3-rich foods are potential browning agents that counteract chronic inflammation and metabolic complications.
Nanoindentation into a bcc high-entropy HfNbTaTiZr alloy—an atomistic study of the effect of short-range order
Authors: Alhafez Iyad Alabd , Deluigi Orlando R. , Tramontina Diego , Merkert Nina , Urbassek Herbert M. , Bringa Eduardo M.
Published: April 2024

The plastic response of the Senkov HfNbTaTiZr high-entropy alloy is explored by means of simulated nanoindentation tests. Both a random alloy and an alloy with chemical short-range order are investigated and compared to the well understood case of an elementary Ta crystal. Strong differences in the dislocation plasticity between the alloys and the elementary Ta crystal are found. The high-entropy alloys show only little relaxation of the indentation dislocation network after indenter retraction and only negligible dislocation emission into the sample interior. Short-range order—besides making the alloy both stiffer and harder—further increases the size of the plastic zone and the dislocation density there. These features are explained by the slow dislocation migration in these alloys. Also, the short-range-ordered alloy features no twinning plasticity in contrast to the random alloy, while elemental Ta exhibits twinning under high stress but detwins considerably under stress relief. The results are in good qualitative agreement with our current knowledge of plasticity in high-entropy alloys.
Optimizing support vector machine (SVM) by social spider optimization (SSO) for edge detection in colored images
Authors: Wang Jianfei
Published: April 2024

Edge detection in images is a vital application of image processing in fields such as object detection and identification of lesion regions in medical images. This problem is more complex in the domain of color images due to the combination of color layer information and the need to achieve a unified edge boundary across these layers, which increases the complexity of the problem. In this paper, a simple and effective method for edge detection in color images is proposed using a combination of support vector machine (SVM) and the social spider optimization (SSO) algorithm. In the proposed method, the input color image is first converted to a grayscale image, and an initial estimation of the image edges is performed based on it. To this end, the proposed method utilizes an SVM with a Radial Basis Function (RBF) kernel, in which the model's hyperparameters are tuned using the SSO algorithm. After the formation of initial image edges, the resulting edges are compared with pairwise combinations of color layers, and an attempt is made to improve the edge localization using the SSO algorithm. In this step, the optimization algorithm's task is to refine the image edges in a way that maximizes the compatibility with pairwise combinations of color layers. This process leads to the formation of prominent image edges and reduces the adverse effects of noise on the final result. The performance of the proposed method in edge detection of various color images has been evaluated and compared with similar previous strategies. According to the obtained results, the proposed method can successfully identify image edges more accurately, as the edges identified by the proposed method have an average accuracy of 93.11% for the BSDS500 database, which is an increase of at least 0.74% compared to other methods.
Rice quality prediction and assessment of pesticide residue changes during storage based on Quatformer
Authors: Jiang Tongqiang , Deng Furong , Dong Wei , Zhang Qingchuan , Liu Peng
Published: April 2024

Rice serves as a fundamental food staple for humans. Its production process, however, unavoidably exposes it to pesticides which may detrimentally impact its quality due to residues. Therefore, it is extremely necessary to monitor pesticide residues on rice during storage. In this research, the Quatformer model, which considers the effects of temperature and humidity on pesticide residues in rice grains, was utilized to forecast the amount of pesticide residues in rice grains during the storage process, and the predicted results were combined with actual observations to form a quality assessment index. By applying the K-Means algorithm, the quality of rice grains was graded and assessed. The findings indicated that the model had high prediction accuracy, and the MAE, MSE, MAPE, RMSE and SMAPE indexes were calculated to be 0.0112, 0.0814, 0.1057, 0.1055 and 0.0204, respectively. These findings provide valuable technical and theoretical support for planning storage conditions, enhancing pesticide residue decomposition, and monitoring rice quality during storage.