bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a ferroptosis-related gene signature to construct diagnostic and prognostic models for assessing immune infiltration in metabolic dysfunction-associated fatty liver disease
Authors: Lian Xin , Tang Xulei 
Published: October 2023

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD), a serious health problem worldwide, can involve ferroptosis. This study aimed to comprehensively analyze the ferroptosis-related genes associated with MAFLD.Methods: Ferroptosis-related differentially expressed genes (FRDEGs) were identified in patients with MAFLD and healthy individuals. Gene ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and gene set enrichment analysis (GSEA) were used to analyze the relevant action pathways of the FRDEGs. The Encyclopedia of RNA Interactomes, CHIPBase, and comparative toxicogenomics databases were used to build mRNA-miRNA, mRNA-transcription factor (TF), and mRNA-drug interaction networks, respectively. A diagnostic model was constructed and bioinformatics analysis methods, such as least absolute shrinkage and selection operator regression analysis, Cox regression analysis, nomogram-based analysis, consensus clustering analysis, and single-sample GSEA, were used to systematically investigate the prognostic values and immunologic characteristics.Results: A total of 13 FRDEGs were obtained and eight were used to construct a diagnostic model and perform a prognostic analysis. Hub genes were also used to construct mRNA-miRNA and mRNA-TF interaction networks and potential drug or molecular compounds. Two MAFLD subtypes were identified: cluster2, which represents an “immunoactive” type, and cluster1, which represents an “immunosuppressive” type; a significant correlation was observed between the immune cell contents and the expression of three FRDEGs (NR4A1, FADS2, and SCD).Conclusion: A ferroptosis-related gene signature was constructed to diagnose MAFLD-associated steatohepatitis, predict the prognosis of MAFLD patients, and analyze the immunologic characteristics of MAFLD. Our findings may provide insights into developing innovative MAFLD treatment techniques.
Modeling and optimization study on degradation of organic contaminants using nZVI activated persulfate based on response surface methodology and artificial neural network: a case study of benzene as the model pollutant
Authors: Luo Moye , Zhang Xiaodong , Long Tao , Chen Sheng , Zhan Manjun , Zhu Xin , Yu Ran 
Published: October 2023

Due to the complicated transport and reactive behavior of organic contamination in groundwater, the development of mathematical models to aid field remediation planning and implementation attracts increasing attentions. In this study, the approach coupling response surface methodology (RSM), artificial neural networks (ANN), and kinetic models was implemented to model the degradation effects of nano-zero-valent iron (nZVI) activated persulfate (PS) systems on benzene, a common organic pollutant in groundwater. The proposed model was applied to optimize the process parameters in order to help predict the effects of multiple factors on benzene degradation rate. Meanwhile, the chemical oxidation kinetics was developed based on batch experiments under the optimized reaction conditions to predict the temporal degradation of benzene. The results indicated that benzene (0.25 mmol) would be theoretically completely oxidized in 1.45 mM PS with the PS/nZVI molar ratio of 4:1 at pH 3.9°C and 21.9 C. The RSM model predicted well the effects of the four factors on benzene degradation rate (R2 = 0.948), and the ANN with a hidden layer structure of [8-8] performed better compared to the RSM (R2 = 0.980). In addition, the involved benzene degradation systems fit well with the Type-2 and Type-3 pseudo-second order (PSO) kinetic models with R2 &gt; 0.999. It suggested that the proposed statistical and kinetic-based modeling approach is promising support for predicting the chemical oxidation performance of organic contaminants in groundwater under the influence of multiple factors.
Sex differences in ventricular arrhythmia, atrial fibrillation and atrioventricular block complicating acute myocardial infarction
Authors: Alnsasra Hilmi , Tsaban Gal , Weinstein Jean Marc , Nasasra Mhamad , Ovdat Tal , Beigel Roy , Orvin Katia , Haim Moti 
Published: October 2023

BackgroundAcute myocardial infarction (AMI) complicated by tachyarrhythmias or high-grade atrioventricular block (HAVB) may lead to increased mortality.PurposeTo evaluate the sex differences in patients with AMI complicated by tachyarrhythmias and HAVB and their associated outcomes.Materials and methodsWe analyzed the incidence rates of arrhythmias following AMI from the Acute Coronary Syndrome Israeli Survey database from 2000 to 2018. We assessed the differences in arrhythmias incidence and the associated mortality risk between men and women.ResultsThis cohort of 14,280 consecutive patients included 3,159 (22.1%) women and 11,121 (77.9%) men. Women were less likely to experience early ventricular tachyarrhythmia (VTA), (1.6% vs. 2.3%, p = 0.034), but had similar rates of late VTA (2.3% vs. 2.2%, p = 0.62). Women were more likely to experience atrial fibrillation (AF) (8.6% vs. 5.0%, p &lt; 0.001) and HAVB (3.7% vs. 2.3%, p &lt; 0.001). The risk of early VTAs was similar in men and women [adjusted Odds Ratio (aOR) = 0.76, p = 0.09], but women had a higher risk of AF (aOR = 1.27, p = 0.004) and HAVB (aOR = 1.30, p = 0.03). Early [adjusted hazard ratio (aHR) = 2.84, p &lt; 0.001] and late VTA (aHR =- 4.59, p &lt; 0.001), AF (aHR = 1.52, p &lt; 0.001) and HAVB (aHR = 2.83, p &lt; 0.001) were associated with increased 30-day mortality. Only late VTA (aHR = 2.14, p &lt; 0.001) and AF (aHR = 1.44, p = 0.002) remained significant in the post 30 days period.ConclusionsDuring AMI women experienced more AF and HAVB but fewer early VTAs than men. Early and late VTAs, AF, and HAVB were associated with increased 30-day mortality. Only late VTA and AF were associated with increased post-30-day mortality.
Portal vein tumour thrombosis radiotherapy improves the treatment outcomes of immunotherapy plus bevacizumab in hepatocellular carcinoma: a multicentre real-world analysis with propensity score matching
Authors: Tang Cuiping , He Qin , Feng Jian , Liao Ziyue , Peng Yunli , Gao Jian 
Published: October 2023

BackgroundThis study aimed to evaluate the efficacy and safety of sequential immune checkpoint inhibitors (ICIs) plus bevacizumab therapy after radiotherapy for portal vein tumour thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC).MethodsRetrospective data were collected from 113 patients with HCC with PVTT. Patients in the PVTT radiotherapy (radiotherapy + ICIs + bevacizumab) and control groups (ICIs + bevacizumab) were enrolled according to propensity score matching (PSM) analysis (1:1). The differences in progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and potential factors affecting PFS between the groups were analysed. The adverse events (AEs) were compared between the two groups.ResultsThere were 47 patients in the two groups after PSM (1:1). The differences in neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), CRP, and CD4, CD8, and CD4-to-CD8 ratio before and after radiotherapy for PVTT (P &lt; 0.05) in the PVTT radiotherapy group were significant. The patients in the PVTT radiotherapy group had a longer PFS (median, 9.6 vs. 5.4 months, P &lt; 0.001), and the PFS rates of 3, 6, 9, and 12 months were 97.87% vs. 94.19%, 80.85% vs. 44.68%, 53.19% vs. 6.38%, and 23.40% vs. 0.00%, respectively (P &lt; 0.001). There were also significant differences in the ORR (48.94% vs. 27.66%, P = 0.0339) and DCR (97.87% vs. 82.98%, P = 0.0141) between the two groups, and no serious AEs were observed. Multivariate Cox analysis showed that AFP expression, gross classification of HCC, PVTT type, extrahepatic metastasis, PVTT radiotherapy, and reduction in PVTT were independent factors influencing PFS (P &lt; 0.05).ConclusionsSequential ICIs plus bevacizumab therapy after radiotherapy for PVTT in patients with HCC is safe and feasible and may further prolong the PFS of patients.
The optimal use of tildrakizumab in the elderly via improvement of Treg function and its preventive effect of psoriatic arthritis
Authors: Fukasawa Takemichi , Yamashita Takashi , Enomoto Atsushi , Norimatsu Yuta , Toyama Satoshi , Yoshizaki-Ogawa Asako , Tateishi Shoko , Kanda Hiroko , Miyagawa Kiyoshi , Sato Shinichi , Yoshizaki Ayumi 
Published: October 2023

IntroductionAs a form of precision medicine, this study aimed to investigate the specific patient population that would derive the greatest benefit from tildrakizumab, as well as the mechanism of action and efficacy of tildrakizumab in reducing the occurrence of psoriatic arthritis (PsA).MethodsTo achieve this, a multi-center, prospective cohort study was conducted, involving a population of 246 psoriasis patients who had not received any systemic therapy or topical finger therapy between January 2020 and April 2023. Two independent clinicians, who were blinded to the study, analyzed nailfold capillary (NFC) abnormalities, such as nailfold bleeding (NFB) and enlarged capillaries, as well as the incidence of new PsA. Additionally, the factors that determined the response of psoriasis after seven months of tildrakizumab treatment were examined. The study also examined the quantity and role of regulatory T cells (Tregs) and T helper 17 cells both pre- and post-treatment.ResultsThe severity of psoriasis, as measured by the Psoriasis Area and Severity Index (PASI), was found to be more pronounced in the tildrakizumab group (n=20) in comparison to the topical group (n=226). At 7 months after tildrakizumab treatment, multivariate analysis showed that those 65 years and older had a significantly better response to treatment in those achieved PASI clear or PASI 2 or less (Likelihood ratio (LR) 16.15, p&lt;0.0001; LR 6. 16, p=0.01). Tildrakizumab improved the number and function of Tregs, which had been reduced by aging. Tildrakizumab demonstrated significant efficacy in improving various pathological factors associated with PsA. These factors include the reduction of NFB, enlargement of capillaries, and inhibition of PsA progression. The hazard ratio for progression to PsA was found to be 0.06 (95% confidence interval: 0.0007-0.46, p=0.007), indicating a substantial reduction in the risk of developing PsA.DiscussionTildrakizumab's effectiveness in improving skin lesions can be attributed to its ability to enhance the number and function of Tregs, which are known to decline with age. Furthermore, the drug's positive impact on NFB activity and capillary enlargement, both of which are recognized as risk factors for PsA, further contribute to its inhibitory effect on PsA progression.
Summer and spring elbow rashes is a variant of polymorphous light eruption: confirmation by photoprovocation and histopathology in a series of five cases
Authors: de Gálvez María Victoria , Castillo-Muñoz Rosa Maria , López-Navarro Norberto , López-Jiménez Patricio , Navarrete-de Gálvez Enrique , Bosch-García Ricardo , Herrera-Acosta Enrique , Aguilera José 
Published: October 2023

BackgroundSummer and spring eruptions on the elbows are a variant of polymorphous light eruption described on clinical and histopathological grounds; however, to our knowledge, they have not been confirmed by photobiological studies.ObjectiveBased on photobiological studies, this study aimed to demonstrate the involvement of ultraviolet-A (UVA) radiation in this variant of polymorphous light eruption occurring exclusively on the elbows.MethodsA series of five patients with polymorphous light eruption lesions on the elbows were included in our study. All patients underwent phototesting and photoprovocation of the skin lesions after exposure to a UVA light source [Philips UVA HPA lamp (400 W)]. All patients underwent punch biopsy and histopathological and immunohistochemical studies with anti-CD123.ResultsIn all the cases, UVA irradiation caused the appearance of skin lesions on the elbows with characteristic polymorphous light eruption. Histological data showed edema in the superficial dermis and a perivascular lymphocytic infiltrate compatible with polymorphous light eruption. Immunohistochemical staining for CD1-23 showed negative results.ConclusionsFor the first time, photobiological photoprovocation studies demonstrated that repeated exposure to UVA radiation leads to the generation of skin lesions on the elbows, which are clinically and histologically consistent with summer and spring eruptions, confirming that elbow rash is a variant of polymorphous light eruption.
Two-carbon tethered artemisinin–isatin hybrids: design, synthesis, anti-breast cancer potential, and in silico study
Authors: Wang Ruo , Huang Renhong , Yuan Yaofeng , Wang Zheng , Shen Kunwei 
Published: October 2023

Eleven two-carbon tethered artemisinin–isatin hybrids (4a–k) were designed, synthesized, and evaluated for their antiproliferative activity against MCF-7, MDA-MB-231, and MDA-MB-231/ADR breast cancer cell lines, as well as cytotoxicity toward MCF-10A cells in this paper. Among them, the representative hybrid 4a (IC50: 2.49–12.6 µM) was superior to artemisinin (IC50: 72.4-&gt;100 µM), dihydroartemisinin (IC50: 69.6–89.8 µM), and Adriamycin (IC50: 4.46–&gt;100 µM) against the three tested breast cancer cell lines. The structure–activity relationship revealed that the length of the alkyl linker between artemisinin and isatin was critical for the activity, so further structural modification could focus on evaluation of the linker. The in silico studies were used to investigate the mechanism of the most promising hybrid 4a. Target prediction, bioinformatics, molecular docking, and molecular dynamics revealed that the most promising hybrid 4a may exert anti-breast cancer activity by acting on multiple targets such as EGFR, PIK3CA, and MAPK8 and thus participating in multiple tumor-related signaling pathways.
Thermal acclimation and habitat-dependent differences in temperature robustness of a crustacean motor circuit
Authors: Stein Wolfgang , Torres Gabriela , Giménez Luis , Espinosa-Novo Noé , Geißel Jan Phillipp , Vidal-Gadea Andrés , Harzsch Steffen 
Published: October 2023

IntroductionAt the cellular level, acute temperature changes alter ionic conductances, ion channel kinetics, and the activity of entire neuronal circuits. This can result in severe consequences for neural function, animal behavior and survival. In poikilothermic animals, and particularly in aquatic species whose core temperature equals the surrounding water temperature, neurons experience rather rapid and wide-ranging temperature fluctuations. Recent work on pattern generating neural circuits in the crustacean stomatogastric nervous system have demonstrated that neuronal circuits can exhibit an intrinsic robustness to temperature fluctuations. However, considering the increased warming of the oceans and recurring heatwaves due to climate change, the question arises whether this intrinsic robustness can acclimate to changing environmental conditions, and whether it differs between species and ocean habitats.MethodsWe address these questions using the pyloric pattern generating circuits in the stomatogastric nervous system of two crab species, Hemigrapsus sanguineus and Carcinus maenas that have seen a worldwide expansion in recent decades.Results and discussionConsistent with their history as invasive species, we find that pyloric activity showed a broad temperature robustness (&gt;30°C). Moreover, the temperature-robust range was dependent on habitat temperature in both species. Warm-acclimating animals shifted the critical temperature at which circuit activity breaks down to higher temperatures. This came at the cost of robustness against cold stimuli in H. sanguineus, but not in C. maenas. Comparing the temperature responses of C. maenas from a cold latitude (the North Sea) to those from a warm latitude (Spain) demonstrated that similar shifts in robustness occurred in natural environments. Our results thus demonstrate that neuronal temperature robustness correlates with, and responds to, environmental temperature conditions, potentially preparing animals for changing ecological conditions and shifting habitats.
Screening of postoperative cerebral hyperperfusion syndrome in moyamoya disease: a three-dimensional pulsed arterial-spin labeling magnetic resonance imaging approach
Authors: Gao Feng , Cong Jianhua , Duan Yu , Zhao Wei , Zhu Zhenfang , Zheng Yu , Jin Liang , Ji Ming , Li Ming 
Published: October 2023

IntroductionMoyamoya disease (MMD) is associated with a risk of postoperative cerebral hyperperfusion syndrome (CHS) after revascularization surgery. This study aimed to explore the feasibility of using three-dimensional pulsed arterial spin labeling (3D PASL) and phase contrast (PC) magnetic resonance imaging (MRI) for predicting CHS occurrence in patients with MMD before revascularization surgery.MethodsOverall, 191 adult patients (207 hemispheres) with MMD who underwent combined revascularization surgery were included in this study. Preoperative 3D PASL-MRI and PC-MRI were performed before surgery. The PASL-MRI data were analyzed using SPM12. Patient clinical information, average flow, and preoperative cerebral blood flow (CBF) were compared between the non-CHS and CHS groups.ResultsAmong the patients, 45 (21.74%) developed CHS after revascularization surgery. No significant differences were noted in age, sex, clinical symptoms, hypertension, diabetes, surgical side, or history of revascularization surgery between the non-CHS and CHS groups. However, the average flow in the superficial temporal artery was significantly lower in the CHS group than in the non-CHS group (p &lt; 0.05). Furthermore, 11 clusters of preoperative CBF values were significantly greater in the CHS group than in the non-CHS group [p &lt; 0.05, false discovery rate (FDR) corrected]. A significant correlation was also observed between the preoperative time-to-flight MR angiography (MRA) scores and CBF values in patients with MMD (p &lt; 0.05).ConclusionCompare patients with lower preoperative CBF and higher preoperative average flow in the STA, patients with higher preoperative CBF and lower preoperative average flow in the STA are more likely to develop postoperative CHS Preoperative PASL-MRI and PC-MRI examinations may help to screen patients at high risk of developing CHS after revascularization surgery.
Temperature modulates PVN pre-sympathetic neurones via transient receptor potential ion channels
Authors: O’Brien Fiona , Feetham Claire H. , Staunton Caroline A. , Hext Kathryn , Barrett-Jolley Richard 
Published: October 2023

The paraventricular nucleus (PVN) of the hypothalamus plays a vital role in maintaining homeostasis and modulates cardiovascular function via autonomic pre-sympathetic neurones. We have previously shown that coupling between transient receptor potential cation channel subfamily V Member 4 (Trpv4) and small-conductance calcium-activated potassium channels (SK) in the PVN facilitate osmosensing, but since TRP channels are also thermosensitive, in this report we investigated the temperature sensitivity of these neurones.Methods: TRP channel mRNA was quantified from mouse PVN with RT-PCR and thermosensitivity of Trpv4-like PVN neuronal ion channels characterised with cell-attached patch-clamp electrophysiology. Following recovery of temperature-sensitive single-channel kinetic schema, we constructed a predictive stochastic mathematical model of these neurones and validated this with electrophysiological recordings of action current frequency.Results: 7 thermosensitive TRP channel genes were found in PVN punches. Trpv4 was the most abundant of these and was identified at the single channel level on PVN neurones. We investigated the thermosensitivity of these Trpv4-like channels; open probability (Po) markedly decreased when temperature was decreased, mediated by a decrease in mean open dwell times. Our neuronal model predicted that PVN spontaneous action current frequency (ACf) would increase as temperature is decreased and in our electrophysiological experiments, we found that ACf from PVN neurones was significantly higher at lower temperatures. The broad-spectrum channel blocker gadolinium (100 µM), was used to block the warm-activated, Ca2+-permeable Trpv4 channels. In the presence of gadolinium (100 µM), the temperature effect was largely retained. Using econazole (10 µM), a blocker of Trpm2, we found there were significant increases in overall ACf and the temperature effect was inhibited.Conclusion: Trpv4, the abundantly transcribed thermosensitive TRP channel gene in the PVN appears to contribute to intrinsic thermosensitive properties of PVN neurones. At physiological temperatures (37°C), we observed relatively low ACf primarily due to the activity of Trpm2 channels, whereas at room temperature, where most of the previous characterisation of PVN neuronal activity has been performed, ACf is much higher, and appears to be predominately due to reduced Trpv4 activity. This work gives insight into the fundamental mechanisms by which the body decodes temperature signals and maintains homeostasis.
Prognostic and predictive value of human equilibrative nucleoside transporter 1 (hENT1) in extrahepatic cholangiocarcinoma: a translational study
Authors: Boyd Lenka N. C. , Nooijen Lynn E. , Ali Mahsoem , Puik Jisce R. , Moustaquim Jasmine , Fraga Rodrigues Stephanie M. , Broos Robert , Belkouz Ali , Meijer Laura L. , Le Large Tessa Y. S. , Erdmann Joris I. , Hooijer Gerrit K. J. , Heger Michal , Van Laarhoven Hanneke W. M. , Roos Eva , Kazemier Geert , Giovannetti Elisa , Verheij Joanne , Klümpen Heinz-Josef 
Published: October 2023

Introduction: Effective (neo) adjuvant chemotherapy for cholangiocarcinoma is lacking due to chemoresistance and the absence of predictive biomarkers. Human equilibrative nucleoside transporter 1 (hENT1) has been described as a potential prognostic and predictive biomarker. In this study, the potential of rabbit-derived (SP120) and murine-derived (10D7G2) antibodies to detect hENT1 expression was compared in tissue samples of patients with extrahepatic cholangiocarcinoma (ECC), and the predictive value of hENT1 was investigated in three ECC cell lines.Methods: Tissues of 71 chemonaïve patients with histological confirmation of ECC were selected and stained with SP120 or 10D7G2 to assess the inter-observer variability for both antibodies and the correlation with overall survival. Concomitantly, gemcitabine sensitivity after hENT1 knockdown was assessed in the ECC cell lines EGI-1, TFK-1, and SK-ChA-1 using sulforhodamine B assays.Results: Scoring immunohistochemistry for hENT1 expression with the use of SP120 antibody resulted in the highest interobserver agreement but did not show a prognostic role of hENT1. However, 10D7G2 showed a prognostic role for hENT1, and a potential predictive role for gemcitabine sensitivity in hENT1 in SK-ChA-1 and TFK-1 cells was found.Discussion: These findings prompt further studies for both preclinical validation of the role of hENT1 and histochemical standardization in cholangiocarcinoma patients treated with gemcitabine-based chemotherapy.