bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of fatty acids synthesis and metabolism-related gene signature and prediction of prognostic model in hepatocellular carcinoma
Authors: Zhengdong Ai , Xiaoying Xing , Shuhui Fu , Rui Liang , Zehui Tang , Guanbin Song , Li Yang , Xi Tang , Wanqian Liu 
Published: April 2024

Abstract
Background
Fatty acids synthesis and metabolism (FASM)-driven lipid mobilization is essential for energy production during nutrient shortages. However, the molecular characteristics, physiological function and clinical prognosis value of FASM-associated gene signatures in hepatocellular carcinoma (HCC) remain elusive.

Methods
The Gene Expression Omnibus database (GEO), the Cancer Genome Atlas (TCGA), and International Cancer Genome Consortium (ICGC) database were utilized to acquire transcriptome data and clinical information of HCC patients. The ConsensusClusterPlus was employed for unsupervised clustering. Subsequently, immune cell infiltration, stemness index and therapeutic response among distinct clusters were decoded. The tumor immune dysfunction and exclusion (TIDE) algorithm was utilized to anticipate the response of patients towards immunotherapy, and the genomics of drug sensitivity in cancer (GDSC) tool was employed to predict their response to antineoplastic medications. Least absolute shrinkage and selection operator (LASSO) regression analysis and protein–protein interaction (PPI) network were employed to construct prognostic model and identity hub gene. Single cell RNA sequencing (scRNA-seq) and CellChat were used to analyze cellular interactions. The hub gene of FASM effect on promoting tumor progression was confirmed through a series of functional experiments.

Results
Twenty-six FASM-related genes showed differential expression in HCC. Based on these FASM-related differential genes, two molecular subtypes were established, including Cluster1 and Cluster2 subtype. Compared with cluster2, Cluster1 subtype exhibited a worse prognosis, higher risk, higher immunosuppressive cells infiltrations, higher immune escape, higher cancer stemness and enhanced treatment-resistant. PPI network identified Acetyl-CoA carboxylase1 (ACACA) as central gene of FASM and predicted a poor prognosis. A strong interaction between cancer stem cells (CSCs) with high expression of ACACA and macrophages through CD74 molecule (CD74) and integrin subunit beta 1 (ITGB1) signaling was identified. Finally, increased ACACA expression was observed in HCC cells and patients, whereas depleted ACACA inhibited the stemness straits and drug resistance of HCC cells.

Conclusions
This study provides a resource for understanding FASM heterogeneity in HCC. Evaluating the FASM patterns can help predict the prognosis and provide new insights into treatment response in HCC patients.
A thermoresponsive nanocomposite integrates NIR-II-absorbing small molecule with lonidamine for pyroptosis-promoted synergistic immunotherapy
Authors: Chen Pengfei , Zhang Chi , He Liuliang , Li Mingfei , Rong Jie , Sun Pengfei , Chen Yingying , Li Daifeng 
Published: April 2024

AbstractPhotothermal immunotherapy is regarded as the ideal cancer therapeutic modality to against malignant solid tumors; however, its therapeutic benefits are often modest and require improvement. In this study, a thermoresponsive nanoparticle (BTN@LND) composed of a photothermal agent (PTA) and pyroptosis inducer (lonidamine) were developed to enhance immunotherapy applications. Specifically, our “two-step” donor engineering strategy produced the strong NIR-II-absorbing organic small-molecule PTA (BTN) that exhibited high NIR-II photothermal performance (ε1064 = 1.51 × 104 M−1 cm−1, η = 75.8%), and this facilitates the diagnosis and treatment of deep tumor tissue. Moreover, the fabricated thermally responsive lipid nanoplatform based on BTN efficiently delivered lonidamine to the tumor site and achieved spatiotemporal release triggered by the NIR-II photothermal effect. In vitro and in vivo experiments demonstrated that the NIR-II photothermal therapy (PTT)-mediated on-demand release of cargo effectively faciliated tumor cell pyroptosis, thereby intensifying the immunogenic cell death (ICD) process to promote antitumor immunotherapy. As a result, this intelligent component bearing photothermal and chemotherapy can maximally suppress the growth of tumors, thus providing a promising approach for pyroptosis/NIR-II PTT synergistic therapy against tumors.
Graphical Abstract
Increased risk of psychiatric disorder in patients with hearing loss: a nationwide population-based cohort study
Authors: Nian Qun-Yi , Cheng Chun-An , Cheng Li-Hsiang , Lin Yuan-Yung , Wang Chin-Hung , Chien Wu-Chien , Chu Yueng-Hsiang , Shih Cheng-Ping , Kuo Chao-Yin , Chen Hsin-Chien , Lee Jih-Chin , Chung Chi-Hsiang , Shangkuan Wei-Chuan , Lin Hung-Che 
Published: April 2024

Abstract
Background
Hearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time.

Methods
This was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The Kaplan‒Meier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders.

Results
A total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P < 0.001). Multivariate analysis indicated that hearing loss significantly elevated the risk of psychiatric disorders (adjusted HR = 2.587, 95% CI 1.723–3.346, p < 0.001).

Conclusion
Our findings indicate that patients with hearing loss are more likely to develop psychiatric disorders. Furthermore, the various psychiatric disorders are more likely to occur at different times. Our findings have important clinical implications, including a need for clinicians to implement early intervention for hearing loss and to pay close attention to patients’ psychological status.
Trial registration TSGHIRB No. E202216036.
Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord
Authors: Huang Jinxin , Hu Xuyang , Chen Zeqiang , Ouyang Fangru , Li Jianjian , Hu Yixue , Zhao Yuanzhe , Wang Jingwen , Yao Fei , Jing Juehua , Cheng Li 
Published: April 2024

Abstract
Background
Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood.

Methods
Spinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery.

Results
Spinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI.

Conclusions
We reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.
SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway
Authors: Yamada Shigeru , Hashita Tadahiro , Yanagida Shota , Sato Hiroyuki , Yasuhiko Yukuto , Okabe Kaori , Noda Takamasa , Nishida Motohiro , Matsunaga Tamihide , Kanda Yasunari 
Published: April 2024

Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is associated with various neurological symptoms, including nausea, dizziness, headache, encephalitis, and epileptic seizures. SARS-CoV-2 is considered to affect the central nervous system (CNS) by interacting with the blood–brain barrier (BBB), which is defined by tight junctions that seal paracellular gaps between brain microvascular endothelial cells (BMECs). Although SARS-CoV-2 infection of BMECs has been reported, the detailed mechanism has not been fully elucidated.

Methods
Using the original strain of SARS-CoV-2, the infection in BMECs was confirmed by a detection of intracellular RNA copy number and localization of viral particles. BMEC functions were evaluated by measuring transendothelial electrical resistance (TEER), which evaluates the integrity of tight junction dynamics, and expression levels of proinflammatory genes. BMEC signaling pathway was examined by comprehensive RNA-seq analysis.

Results
We observed that iPSC derived brain microvascular endothelial like cells (iPSC-BMELCs) were infected with SARS-CoV-2. SARS-CoV-2 infection resulted in decreased TEER. In addition, SARS-CoV-2 infection decreased expression levels of tight junction markers CLDN3 and CLDN11. SARS-CoV-2 infection also increased expression levels of proinflammatory genes, which are known to be elevated in patients with COVID-19. Furthermore, RNA-seq analysis revealed that SARS-CoV-2 dysregulated the canonical Wnt signaling pathway in iPSC-BMELCs. Modulation of the Wnt signaling by CHIR99021 partially inhibited the infection and the subsequent inflammatory responses.

Conclusion
These findings suggest that SARS-CoV-2 infection causes BBB dysfunction via Wnt signaling. Thus, iPSC-BMELCs are a useful in vitro model for elucidating COVID-19 neuropathology and drug development.
Optimization of preparation conditions for Salsola laricifolia protoplasts using response surface methodology and artificial neural network modeling
Authors: Guo Hao , Xi Yuxin , Guzailinuer Kuerban , Wen Zhibin 
Published: April 2024

Abstract
Background
Salsola laricifolia is a typical C3–C4 typical desert plant, belonging to the family Amaranthaceae. An efficient single-cell system is crucial to study the gene function of this plant. In this study, we optimized the experimental conditions by using Box-Behnken experimental design and Response Surface Methodology (RSM)-Artificial Neural Network (ANN) model based on the previous studies.

Results
Among the 17 experiment groups designed by Box-Behnken experimental design, the maximum yield (1.566 × 106/100 mg) and the maximum number of viable cells (1.367 × 106/100 mg) were obtained in group 12, and the maximum viability (90.81%) was obtained in group 5. Based on these results, both the RSM and ANN models were employed for evaluating the impact of experimental factors. By RSM model, cellulase R-10 content was the most influential factor on protoplast yield, followed by macerozyme R-10 content and mannitol concentration. For protoplast viability, the macerozyme R-10 content had the highest influence, followed by cellulase R-10 content and mannitol concentration. The RSM model performed better than the ANN model in predicting yield and viability. However, the ANN model showed significant improvement in predicting the number of viable cells. After comprehensive evaluation of the protoplast yield, the viability and number of viable cells, the optimal results was predicted by ANN yield model and tested. The amount of protoplast yield was 1.550 × 106/100 mg, with viability of 90.65% and the number of viable cells of 1.405 × 106/100 mg. The corresponding conditions were 1.98% cellulase R-10, 1.00% macerozyme R-10, and 0.50 mol L−1 mannitol. Using the obtained protoplasts, the reference genes (18SrRNA, β-actin and EF1-α) were screened for expression, and transformed with PEG-mediated pBI121-SaNADP-ME2-GFP plasmid vector. There was no significant difference in the expression of β-actin and EF1-α before and after treatment, suggesting that they can be used as internal reference genes in protoplast experiments. And SaNADP-ME2 localized in chloroplasts.

Conclusion
The current study validated and evaluated the effectiveness and results of RSM and ANN in optimizing the conditions for protoplast preparation using S. laricifolia as materials. These two methods can be used independently of experimental materials, making them suitable for isolating protoplasts from other plant materials. The selection of the number of viable cells as an evaluation index for protoplast experiments is based on its ability to consider both protoplast yield and viability. The findings of this study provide an efficient single-cell system for future genetic experiments in S. laricifolia and can serve as a reference method for preparing protoplasts from other materials.
Medicine, emotience, and reason
Authors: Clark John F. 
Published: April 2024

AbstractMedicine is faced with a number of intractable modern challenges that can be understood in terms of hyper-intellectualization; a compassion crisis, burnout, dehumanization, and lost meaning. These challenges have roots in medical philosophy and indeed general Western philosophy by way of the historic exclusion of human emotion from human reason. The resolution of these medical challenges first requires a novel philosophic schema of human knowledge and reason that incorporates the balanced interaction of human intellect and human emotion. This schema of necessity requires a novel extension of dual-process theory into epistemology in terms of both intellect and emotion each generating a distinct natural kind of knowledge independent of the other as well as how these two forms of mental process together construct human reason. Such a novel philosophic schema is here proposed. This scheme is then applied to the practice of medicine with examples of practical applications with the goal of reformulating medical practice in a more knowledgable, balanced, and healthy way. This schema’s expanded epistemology becomes the philosophic foundation for more fully incorporating the humanities in medicine.
Application direct anterior approach in pediatric femoral head and neck lesions
Authors: Zheng Jian , Zhang Yanting , Nan Guoxin 
Published: April 2024

Abstract
Background
Femoral neck is one of the high-risk areas for benign tumors and tumor-like lesions. Small range of lesions may also lead to pathological fracture, femoral head necrosis and other serious problems.

Purpose
To investigate a new minimally invasive surgical approach to resect femoral head and neck lesions in children.

Patients and methods
Retrospective study of 20 patients with femoral neck and femoral head lesions from February 2019 to March 2023 in our hospital. Among them, 14 were boys and 6 were girls, 17 were femoral neck lesions and 3 were femoral head lesions. The age of the patients ranged from 3.2 to 12.6 years, with a mean of 7.1 years. The patients were divided into group A and group B according to different surgical approaches; group A used the Smith-Peterson approach, Watson-Jones approach or surgical dislocation approach and group B used the DAA. Intra-operatively, incision length, operative time and blood loss were recorded in both groups. Group A consisted of 1 femoral head lesion and 8 femoral neck lesions, including 5 cases of bone cyst and 4 cases of eosinophilic granuloma. Group B consisted of 2 femoral head lesion and 9 femoral neck lesions. A total of 11 patients with different types of disease were included in group B, including bone cysts (3 cases), aneurysmal bone cysts (1 case), eosinophilic granulomas (6 cases), Kaposi's sarcoma (1 case).

Results
The two groups of patients differed in terms of incision length (P < 0.05), operative blood loss (P < 0.05) and operative time (P < 0.05). At 6–48 months post-operatively, there were no significant differences in function and all patients had good hip function.

Conclusion
The direct anterior approach is effective for resection of paediatric femoral head and neck lesions. It provides clear exposure of the surgical site, minimal trauma and does not compromise the integrity of the anterior musculature.
Level of evidence: III.
Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder
Authors: Chen Chen , Xu Jian-Lin , Gu Zhan-Cheng , Zhou Shan-Shan , Wei Guo-Li , Gu Jia-Lin , Ma Hai-Long , Feng Yan-Qi , Song Zi-Wei , Yan Zhan-Peng , Deng Shan , Ding Rong , Li Song-Lin , Huo Jie-Ge 
Published: April 2024

Abstract
Background
Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated.

Methods
The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation.

Results
DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, l-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota.

Conclusion
DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.
Application of immersive virtual reality in the training of wheelchair boxers: evaluation of exercise intensity and users experience additional load– a pilot exploratory study
Authors: Polechoński Jacek , Langer Alan , Akbaş Anna , Zwierzchowska Anna 
Published: April 2024

Abstract
Background
Over the last few years, there has been a growing interest in workout apps and active virtual reality video games (AVRGs), which provide entertainment and enable users to undertake various forms of physical activity (PA) at home. Presumably, these types of exercises can be particularly useful for people with physical disabilities, who experience problems with access to sports and leisure facilities due to architectural and communication barriers. However, it is interesting whether the intensity of PA in VR is high enough to provide users with health benefits, as it is mainly based on arm movements.

Objective
The main aim of the study was to evaluate the intensity of physical exercise of wheelchair boxers during a boxing training session using the FitXR app in immersive VR in light of health-related PA recommendations. The effect of Velcro-fastened hand-held weights (HHWs) on the intensity of PA undertaken by people in VR was also examined, and the attractiveness of virtual exercise were assessed in the opinion of users.

Methods
PA intensity was evaluated using a heart rate monitor based on the percentage of maximal heart rate (% HRmax) and the Borg’s rating of perceived exertion (RPE 6–20). The attractiveness perceived during exercise by users were evaluated using the Physical Activity Enjoyment Scale (PACES 1–7 scale).

Results
The study shows that the exercise intensity of the athletes during wheelchair boxing training in VR is at a beneficial moderate level for health (HRave=68.98% HRmax). The use of HHWs (0.5 kg) does not significantly increase the PA intensity of the individuals during virtual exercise. Users with disabilities highly rated the attractiveness (6.32 ± 0.79 points) of PA during virtual boxing training.

Conclusions
Boxing exercises in VR can be an attractive and health-related form of PA for wheelchair boxers and a supplement to their conventional training.
Comprehensive machine learning boosts structure-based virtual screening for PARP1 inhibitors
Authors: Caba Klaudia , Tran-Nguyen Viet-Khoa , Rahman Taufiq , Ballester Pedro J. 
Published: April 2024

AbstractPoly ADP-ribose polymerase 1 (PARP1) is an attractive therapeutic target for cancer treatment. Machine-learning scoring functions constitute a promising approach to discovering novel PARP1 inhibitors. Cutting-edge PARP1-specific machine-learning scoring functions were investigated using semi-synthetic training data from docking activity-labelled molecules: known PARP1 inhibitors, hard-to-discriminate decoys property-matched to them with generative graph neural networks and confirmed inactives. We further made test sets harder by including only molecules dissimilar to those in the training set. Comprehensive analysis of these datasets using five supervised learning algorithms, and protein–ligand fingerprints extracted from docking poses and ligand only features revealed one highly predictive scoring function. This is the PARP1-specific support vector machine-based regressor, when employing PLEC fingerprints, which achieved a high Normalized Enrichment Factor at the top 1% on the hardest test set (NEF1% = 0.588, median of 10 repetitions), and was more predictive than any other investigated scoring function, especially the classical scoring function employed as baseline.