bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the supraspinal sensorimotor control of walking using MRI-compatible system: a systematic review
Authors: Hong Yinglu , Bao Dapeng , Manor Brad , Zhou Junhong 
Published: March 2024

Abstract
Background
The regulation of gait is critical to many activities of everyday life. When walking, somatosensory information obtained from mechanoreceptors throughout body is delivered to numerous supraspinal networks and used to execute the appropriate motion to meet ever-changing environmental and task demands. Aging and age-related conditions oftentimes alter the supraspinal sensorimotor control of walking, including the responsiveness of the cortical brain regions to the sensorimotor inputs obtained from the peripheral nervous system, resulting in diminished mobility in the older adult population. It is thus important to explicitly characterize such supraspinal sensorimotor elements of walking, providing knowledge informing novel rehabilitative targets. The past efforts majorly relied upon mental imagery or virtual reality to study the supraspinal control of walking. Recent efforts have been made to develop magnetic resonance imaging (MRI)-compatible devices simulating specific somatosensory and/or motor aspects of walking. However, there exists large variance in the design and functionality of these devices, and as such inconsistent functional MRI (fMRI) observations.

Methods
We have therefore completed a systematic review to summarize current achievements in the development of these MRI-compatible devices and synthesize available imaging results emanating from studies that have utilized these devices.

Results
The device design, study protocol and neuroimaging observations of 26 studies using 13 types of devices were extracted. Three of these devices can provide somatosensory stimuli, eight motor stimuli, and two both types of stimuli. Our review demonstrated that using these devices, fMRI data of brain activation can be successfully obtained when participants remain motionless and experience sensorimotor stimulation during fMRI acquisition. The activation in multiple cortical (e.g., primary sensorimotor cortex) and subcortical (e.g., cerebellum) regions has been each linked to these types of walking-related sensorimotor stimuli.

Conclusion
The observations of these publications suggest the promise of implementing these devices to characterize the supraspinal sensorimotor control of walking. Still, the evidence level of these neuroimaging observations was still low due to small sample size and varied study protocols, which thus needs to be confirmed via studies with more rigorous design.
The POU-HD TFs impede the replication efficiency of several human papillomavirus genomes
Authors: Kala Martin , Babok Sofiya , Mikhailava Nika , Piirsoo Marko , Piirsoo Alla 
Published: March 2024

AbstractHuman papillomavirus (HPV) is a double-stranded DNA virus that infects cutaneous and mucosal epithelial cells. HPV replication initiates at the origin (ori), located within a noncoding region near the major early promoter. Only two viral proteins, E1 and E2, are essential for replication, with the host cell contributing other necessary factors. However, the role of host cell proteins in regulating HPV replication remains poorly understood. While several binding sites for cellular transcription factors (TFs), such as POU-HD proteins, have been mapped in the regulatory region, their functional importance is unclear. Some POU-HD TFs have been shown to influence replication in a system where E1 and E2 are provided exogenously. In this study, we investigated the impact of several POU-HD TFs on the replication of the HPV5, HPV11, and HPV18 genomes in U2OS cells and human primary keratinocytes. We demonstrated that OCT1, OCT6, BRN5A, and SKN1A are expressed in HPV host cells and that their overexpression inhibits HPV genome replication, whereas knocking down OCT1 had a positive effect. Using the replication-deficient HPV18-E1− genome, we demonstrated that OCT1-mediated inhibition of HPV replication involves modulation of HPV early promoters controlling E1 and E2 expression. Moreover, using Oct6 mutants deficient either in DNA binding or transcriptional regulation, we showed that the inhibition of HPV18 replication is solely dependent on Oct6’s DNA binding activity. Our study highlights the complex regulatory roles of POU-HD factors in the HPV replication.
Does unequal economic development contribute to the inequitable distribution of healthcare resources? Evidence from China spanning 2001–2020
Authors: Qin Afei , Qin Wenzhe , Hu Fangfang , Wang Meiqi , Yang Haifeng , Li Lei , Chen Chiqi , Bao Binghong , Xin Tianjiao , Xu Lingzhong 
Published: March 2024

Abstract
Background
There is a dearth of research combining geographical big data on medical resource allocation and growth with various statistical data. Given the recent achievements of China in economic development and healthcare, this study takes China as an example to investigate the dynamic geographical distribution patterns of medical resources, utilizing data on healthcare resources from 290 cities in China, as well as economic and population-related data. The study aims to examine the correlation between economic growth and spatial distribution of medical resources, with the ultimate goal of providing evidence for promoting global health equity.

Methods
The data used in this study was sourced from the China City Statistical Yearbook from 2001 to 2020. Two indicators were employed to measure medical resources: the number of doctors per million population and the number of hospital and clinic beds per million population. We employed dynamic convergence model and fixed-effects model to examine the correlation between economic growth and the spatial distribution of medical resources. Ordinary least squares (OLS) were used to estimate the β values of the samples.

Results
The average GDP for all city samples across all years was 36,019.31 ± 32,029.36, with an average of 2016.31 ± 1104.16 doctors per million people, and an average of 5986.2 ± 6801.67 hospital beds per million people. In the eastern cities, the average GDP for all city samples was 47,672.71 ± 37,850.77, with an average of 2264.58 ± 1288.89 doctors per million people, and an average of 3998.92 ± 1896.49 hospital beds per million people. Cities with initially low medical resources experienced faster growth (all β < 0, P < 0.001). The long-term convergence rate of the geographic distribution of medical resources in China was higher than the short-term convergence rate (|βi + 1| > |βi|, i = 1, 2, 3, …, 9, all β < 0, P < 0.001), and the convergence speed of doctor density exceeded that of bed density (bed: |βi| >doc: |βi|, i = 3, 4, 5, …, 10, P < 0.001). Economic growth significantly affected the convergence speed of medical resources, and this effect was nonlinear (doc: βi < 0, i = 1, 2, 3, …, 9, P < 0.05; bed: βi < 0, i = 1, 2, 3, …, 10, P < 0.01). The heterogeneity between provinces had a notable impact on the convergence of medical resources.

Conclusions
The experiences of China have provided significant insights for nations worldwide. Governments and institutions in all countries worldwide, should actively undertake measures to actively reduce health inequalities. This includes enhancing healthcare standards in impoverished regions, addressing issues of unequal distribution, and emphasizing the examination of social determinants of health within the domain of public health research.
Cayratia albifolia C.L.Li exerts anti-rheumatoid arthritis effect by inhibiting macrophage activation and neutrophil extracellular traps (NETs)
Authors: Wang Wei , Zhang Zai-Qi , Zhang Yi-Chi , Wu Yi-Qiang , Yang Zhuo , Zheng Yong-Zhe , Lu Jia-Hong , Tu Peng-Fei , Zeng Ke-Wu 
Published: March 2024

Abstract
Background
Cayratia albifolia C.L.Li (CAC), commonly known as “Jiao-Mei-Gu” in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established.

Methods
Twenty-four Sprague–Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot.

Results
CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA.

Conclusions
We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation.

Graphical Abstract
MOCAT: multi-omics integration with auxiliary classifiers enhanced autoencoder
Authors: Yao Xiaohui , Jiang Xiaohan , Luo Haoran , Liang Hong , Ye Xiufen , Wei Yanhui , Cong Shan 
Published: March 2024

AbstractBackgroundIntegrating multi-omics data is emerging as a critical approach in enhancing our understanding of complex diseases. Innovative computational methods capable of managing high-dimensional and heterogeneous datasets are required to unlock the full potential of such rich and diverse data.MethodsWe propose a Multi-Omics integration framework with auxiliary Classifiers-enhanced AuToencoders (MOCAT) to utilize intra- and inter-omics information comprehensively. Additionally, attention mechanisms with confidence learning are incorporated for enhanced feature representation and trustworthy prediction.ResultsExtensive experiments were conducted on four benchmark datasets to evaluate the effectiveness of our proposed model, including BRCA, ROSMAP, LGG, and KIPAN. Our model significantly improved most evaluation measurements and consistently surpassed the state-of-the-art methods. Ablation studies showed that the auxiliary classifiers significantly boosted classification accuracy in the ROSMAP and LGG datasets. Moreover, the attention mechanisms and confidence evaluation block contributed to improvements in the predictive accuracy and generalizability of our model.ConclusionsThe proposed framework exhibits superior performance in disease classification and biomarker discovery, establishing itself as a robust and versatile tool for analyzing multi-layer biological data. This study highlights the significance of elaborated designed deep learning methodologies in dissecting complex disease phenotypes and improving the accuracy of disease predictions.
Mutant α-synuclein causes death of human cortical neurons via ERK1/2 and JNK activation
Authors: Suzuki Hidefumi , Egawa Naohiro , Imamura Keiko , Kondo Takayuki , Enami Takako , Tsukita Kayoko , Suga Mika , Yada Yuichiro , Shibukawa Ran , Takahashi Ryosuke , Inoue Haruhisa 
Published: March 2024

AbstractSynucleinopathies refer to a group of disorders characterized by SNCA/α-synuclein (α-Syn)-containing cytoplasmic inclusions and neuronal cell loss in the nervous system including the cortex, a common feature being cognitive impairment. Still, the molecular pathogenesis of cognitive decline remains poorly understood, hampering the development of effective treatments. Here, we generated induced pluripotent stem cells (iPSCs) derived from familial Parkinson’s disease (PD) patients carrying SNCA A53T mutation, differentiating them into cortical neurons by a direct conversion method. Patient iPSCs-derived cortical neurons harboring mutant α-Syn exhibited increased α-Syn-positive aggregates, shorter neurites, and time-dependent vulnerability. Furthermore, RNA-sequencing analysis, followed by biochemical validation, identified the activation of the ERK1/2 and JNK cascades in cortical neurons with SNCA A53T mutation. This result was consistent with a reverted phenotype of neuronal death in cortical neurons when treated with ERK1/2 and JNK inhibitors, respectively. Our findings emphasize the role of ERK1/2 and JNK cascades in the vulnerability of cortical neurons in synucleinopathies, and they could pave the way toward therapeutic advancements for synucleinopathies.
KLF7 regulates super-enhancer-driven IGF2BP2 overexpression to promote the progression of head and neck squamous cell carcinoma
Authors: Cai Hongshi , Liang Jianfeng , Jiang Yaoqi , Wang Ziyi , Li Hongyu , Wang Wenjin , Wang Cheng , Hou Jinsong 
Published: March 2024

Abstract
Background
Head and neck squamous carcinoma (HNSCC) is known for its high aggressiveness and susceptibility to cervical lymph node metastasis, which greatly contributes to its poor prognosis. During tumorigenesis, many types of cancer cells acquire oncogenic super-enhancers (SEs) that drive the overexpression of oncogenes, thereby maintaining malignant progression. This study aimed to identify and validate the role of oncogenic SE-associated genes in the malignant progression of HNSCC.

Methods
We identified HNSCC cell-specific SE-associated genes through H3K27Ac ChIP-seq and overlapped them with HNSCC-associated genes obtained from The Cancer Genome Atlas (TCGA) dataset and Gene Expression Omnibus (GEO) datasets using weighted gene coexpression network analysis (WGCNA) to identify hub genes. The expression of IGF2BP2 and KLF7 in HNSCC was detected using clinical samples. To determine the biological role of IGF2BP2, we performed CCK-8, colony formation assay, Transwell migration assay, invasion assay, and orthotopic xenograft model experiments. Furthermore, we utilized a CRISPR/Cas9 gene-editing system, small-molecule inhibitors, ChIP-qPCR, and dual-luciferase reporter assays to investigate the molecular mechanisms of IGF2BP2 and its upstream transcription factors.

Results
Our study identified IGF2BP2 as a hub SE-associated gene that exhibited aberrant expression in HNSCC tissues. Increased expression of IGF2BP2 was observed to be linked with malignant progression and unfavorable prognosis in HNSCC patients. Both in vitro and in vivo experiments confirmed that IGF2BP2 promotes the tumorigenicity and metastasis of HNSCC by promoting cell proliferation, migration, and invasion. Mechanistically, the IGF2BP2-SE region displayed enrichment for H3K27Ac, BRD4, and MED1, which led to the inhibition of IGF2BP2 transcription and expression through deactivation of the SE-associated transcriptional program. Additionally, KLF7 was found to induce the transcription of IGF2BP2 and directly bind to its promoter and SE regions. Moreover, the abundance of KLF7 exhibited a positive correlation with the abundance of IGF2BP2 in HNSCC. Patients with high expression of both KLF7 and IGF2BP2 showed poorer prognosis. Lastly, we demonstrated that the small molecule inhibitor JQ1, targeting BRD4, attenuated the proliferation and metastatic abilities of HNSCC cells.

Conclusions
Our study reveals the critical role of IGF2BP2 overexpression mediated by SE and KLF7 in promoting HNSCC progression. Targeting SE-associated transcriptional programs may represent a potential therapeutic strategy in managing HNSCC.
A real-world study of treatment patterns following disease progression in epithelial ovarian cancer patients undergoing poly-ADP-ribose polymerase inhibitor maintenance therapy
Authors: Zhang Nan , Zheng Hong , Gao Yunong , Shu Tong , Wang Hongguo , Cai Yan 
Published: March 2024

Abstract
Background
The efficacy of subsequent therapy after poly-ADP-ribose polymerase (PARP) inhibitor maintenance treatment has raised concerns. Retrospective studies show worse outcomes for platinum-based chemotherapy after progression of PARP inhibitor-maintenance therapy, especially in BRCA-mutant patients. We aimed to describe subsequent therapy in ovarian cancer patients after PARP inhibitor-maintenance therapy and evaluate their response to treatment. We focused on chemotherapy for patients with a progression-free interval (PFI) of ≥ 6 months after prior platinum treatment, based on BRCA status.

Methods
We analyzed real-world data from Peking University Cancer Hospital, subsequent therapy after progression to PARP inhibitor-maintenance therapy for epithelial ovarian cancer between January 2016 and December 2022. Clinicopathological characteristics and treatment outcomes were extracted from medical records. The last follow-up was in May 2023.

Results
A total of 102 patients were included, of which 29 (28.4%) had a germline BRCA1/2 mutation and 73 (71.6%) exhibited BRCA1/2 wild-type mutations. The PARP inhibitors used were Olaparib (n = 62, 60.8%), Niraparib (n = 35, 34.3%), and others (n = 5, 4.9%). The overall response rate (ORR) was 41.2%, and the median time to second progression (mTTSP) was 8.1 months (95%CI 5.8–10.2). Of 91 platinum-sensitive patients (PFI ≥ 6 months) after progression to PARP inhibitor-maintenance therapy, 65 patients subsequently received platinum regimens. Among them, 30 had received one line of chemotherapy before PARP inhibitor-maintenance therapy. Analysis of these 30 patients by BRCA status showed an ORR of 16.7% versus 33.3% and mTTSP of 7.1 (95% CI 4.9–9.1) versus 6.2 months (95% CI 3.7–8.3, P = 0.550), for BRCA-mutant and wild-type patients, respectively. For the remaining 35 patients who had received two or more lines of chemotherapy before PARP inhibitor-maintenance therapy, ORR was 57.1% versus 42.9%, and mTTSP was 18.0 (95% CI 5.0–31.0) versus 8.0 months (95% CI 4.9–11.1, P = 0.199), for BRCA-mutant and wild-type patients, respectively.

Conclusion
No differences in survival outcomes were observed among patients with different BRCA statuses. Furthermore, for patients who had undergone two or more lines of chemotherapy before PARP inhibitor maintenance therapy, no negative effects of PARP inhibitors on subsequent treatment were found, regardless of BRCA status.
Fatal food anaphylaxis in adults and children
Authors: Novembre Elio , Gelsomino Mariannita , Liotti Lucia , Barni Simona , Mori Francesca , Giovannini Mattia , Mastrorilli Carla , Pecoraro Luca , Saretta Francesca , Castagnoli Riccardo , Arasi Stefania , Caminiti Lucia , Klain Angela , del Giudice Michele Miraglia 
Published: March 2024

AbstractAnaphylaxis is a life-threatening reaction characterized by the acute onset of symptoms involving different organ systems and requiring immediate medical intervention. The incidence of fatal food anaphylaxis is 0.03 to 0.3 million/people/year. Most fatal food-induced anaphylaxis occurs in the second and third decades of life. The identified risk factors include the delayed use of epinephrine, the presence of asthma, the use of recreational drugs (alcohol, nicotine, cannabis, etc.), and an upright position. In the United Kingdom (UK) and Canada, the reported leading causal foods are peanuts and tree nuts. In Italy, milk seems to be the most common cause of fatal anaphylaxis in children < 18 years. Fatal food anaphylaxis in Italian children and adolescents almost always occurs outside and is characterized by cardiorespiratory arrest; auto-injectable adrenaline intramuscular was available in few cases. Mortality from food anaphylaxis, especially in children, is a very rare event with stable incidence, but its risk deeply impacts the quality of life of patients with food allergy and their families. Prevention of fatal food anaphylaxis must involve patients and their families, as well as the general public, public authorities, and patients’ associations.
Severe fever with thrombocytopenia syndrome virus infection shapes gut microbiome of the tick vector Haemaphysalis longicornis
Authors: Sun Yu , Chen Chen , Zeng Chenghong , Xia Qianfeng , Yuan Chuanfei , Pei Hua 
Published: March 2024

Abstract
Background
Ticks serve as vectors for a diverse array of pathogens, including viruses responsible for both human and livestock diseases. Symbiotic bacteria hold significant potential for controlling tick-borne disease. However, the alteration of tick gut bacterial community in response to pathogen infection has not been analyzed for any tick-borne viruses. Here, the impact of severe fever with thrombocytopenia syndrome virus (SFTSV) infection on bacterial diversity in the gut of Haemaphysalis longicornis is investigated.

Methods
Unfed tick females were artificially infected with SFTSV. The gut samples were collected and the genomic DNA was extracted. We then investigated alterations in gut bacterial composition in response to SFTSV infection through 16S rRNA gene sequencing.

Results
The study found that a reduction in the number of operational taxonomic units (OTUs) in the tick gut following SFTSV infection. However, there were no significant changes in alpha diversity indices upon infection. Four genera, including Corynebacterium, Arthrobacter, Sphingomonas, and Escherichia, were identified as biomarkers for the tick gut without SFTSV infection. Notably, the predicted correlation network indicated that the biomarkers Sphingomonas and Escherichia exhibited positive correlations within the same subcommunity, which was altered upon viral infection.

Conclusions
These findings revealed that the change in tick gut bacterial composition upon SFTSV infection and could facilitate the discovery new target for tick-borne viral disease control.

Graphical Abstract