bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-intensity pulsed ultrasound (LIPUS) enhances the anti-inflammatory effects of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles
Authors: Li Xueke , Zhong Yi , Zhou Wuqi , Song Yishu , Li Wenqu , Jin Qiaofeng , Gao Tang , Zhang Li , Xie Mingxing 
Published: January 2023

AbstractBackgroundBone marrow-derived mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) have shown potent anti-inflammatory function in various pathological conditions, such as osteoarthritis and neurodegenerative diseases. Since the number of EVs naturally secreted by cells is finite and they usually bear specific repertoires of bioactive molecules to perform manifold cell–cell communication, but not one particular therapeutic function as expected, their practical application is still limited. Strategies are needed to increase the production of EVs and enhance their therapeutic function. Recent studies have suggested that low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive method to increase the secretion of EVs and promote their anti-inflammatory effects. However, the effect of LIPUS stimulation of BMSCs on EVs derived from the cells remains unclear. The objective of this study was to investigate whether LIPUS stimulation on BMSCs could increase the secretion of EVs and enhance their anti-inflammatory effects.MethodsBMSCs were exposed to LIPUS (300 mW/cm2) for 15 min and EVs were isolated by ultracentrifugation. Anti-inflammatory effects of EVs were investigated on RAW264.7 cells in vitro and in the allogeneic skin transplantation model. Small RNA-seq was utilized to identify components difference in EVs with/without LIPUS irradiation.ResultsIn this study, we found that LIPUS stimulation could lead to a 3.66-fold increase in the EVs release from BMSCs. Moreover, both in vitro and in vivo experimental results suggested that EVs secreted from LIPUS-treated BMSCs (LIPUS-EVs) possessed stronger anti-inflammatory function than EVs secreted from BMSCs without LIPUS stimulation (C-EVs). RNA-seq analysis revealed that miR-328-5p and miR-487b-3p were significantly up-regulated in LIPUS-EVs compare with C-EVs. The suppression of MAPK signaling pathway by these two up-regulated miRNAs could be the potential mechanism of strengthened anti-inflammatory effects of LIPUS-EVs.ConclusionLIPUS stimulation on BMSCs could significantly increase the secretion of EVs. Moreover, EVs generated from LIPUS-treated BMSCs possessed much stronger anti-inflammatory function than C-EVs. Therefore, LIPUS could be a promising non-invasive strategy to promote the production of EVs from BMSCs and augment their anti-inflammatory effects.
Clinical relationship between dry eye disease and uveitis: a scoping review
Authors: Rojas-Carabali William , Mejía-Salgado Germán , Cifuentes-González Carlos , Villabona-Martínez Valeria , Barraquer-López Nicolás Doménico , Valdés-Arias David , de-la-Torre Alejandra 
Published: January 2023

AbstractThis scoping review examined the relationship between Dry Eye Disease (DED) and Uveitis. We searched Pubmed, Embase, and LILACS databases for articles in which at least one patient had DED and uveitis concomitantly. The search produced 2381 records, and 24 studies were included in the qualitative synthesis. We concluded that DED and uveitis of any etiology could appear concomitantly in patients of any age. However, both diseases seem to coexist more frequently in middle-aged women and cases of anterior uveitis. Therefore, it is crucial that ophthalmologists actively look for the coexistence of ocular surface abnormalities, especially in patients with these characteristics. Future studies should establish and quantify the risk factors and pathophysiological mechanisms of this coexistence to achieve an early diagnosis of both etiologies and comprehensive management of these patients.
Bradyrhizobium japonicum IRAT FA3 promotes salt tolerance through jasmonic acid priming in Arabidopsis thaliana
Authors: Gomez Melissa Y. , Schroeder Mercedes M. , Chieb Maha. , McLain Nathan K. , Gachomo Emma W. 
Published: January 2023

Abstract
Background
Plant growth promoting rhizobacteria (PGPR), such as Bradyrhizobium japonicum IRAT FA3, are able to improve seed germination and plant growth under various biotic and abiotic stress conditions, including high salinity stress. PGPR can affect plants’ responses to stress via multiple pathways which are often interconnected but were previously thought to be distinct. Although the overall impacts of PGPR on plant growth and stress tolerance have been well documented, the underlying mechanisms are not fully elucidated. This work contributes to understanding how PGPR promote abiotic stress by revealing major plant pathways triggered by B. japonicum under salt stress.

Results
The plant growth-promoting rhizobacterial (PGPR) strain Bradyrhizobium japonicum IRAT FA3 reduced the levels of sodium in Arabidopsis thaliana by 37.7%. B. japonicum primed plants as it stimulated an increase in jasmonates (JA) and modulated hydrogen peroxide production shortly after inoculation. B. japonicum-primed plants displayed enhanced shoot biomass, reduced lipid peroxidation and limited sodium accumulation under salt stress conditions. Q(RT)-PCR analysis of JA and abiotic stress-related gene expression in Arabidopsis plants pretreated with B. japonicum and followed by six hours of salt stress revealed differential gene expression compared to non-inoculated plants. Response to Desiccation (RD) gene RD20 and reactive oxygen species scavenging genes CAT3 and MDAR2 were up-regulated in shoots while CAT3 and RD22 were increased in roots by B. japonicum, suggesting roles for these genes in B. japonicum-mediated salt tolerance. B. japonicum also influenced reductions of RD22, MSD1, DHAR and MYC2 in shoots and DHAR, ADC2, RD20, RD29B, GTR1, ANAC055, VSP1 and VSP2 gene expression in roots under salt stress.

Conclusion
Our data showed that MYC2 and JAR1 are required for B. japonicum-induced shoot growth in both salt stressed and non-stressed plants. The observed microbially influenced reactions to salinity stress in inoculated plants underscore the complexity of the B. japonicum jasmonic acid-mediated plant response salt tolerance.
Analysis of related factors of portal vein thrombosis in liver cirrhosis
Authors: Xu Xiaotong , Jin Jinglan , Liu Yuwei , Li Hang 
Published: January 2023

Abstract
Background and aims
To investigate the usefulness of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), protein C (PC), and thromboelastography (TEG) to serve as a predictor of portal vein thrombosis (PVT) in patients with liver cirrhosis. Additionally, we examined the clinical significance of the above indicators in terms of disease progression.

Methods
A total of 123 patients with liver cirrhosis were recruited from May 2021 to December 2021, according to the imaging findings. They were divided into the PVT group (n = 52) and the non-PVT group (n = 71). Furthermore, patients with PVT were divided into plasma transfusion groups (n = 13) and non-plasma transfusion groups (n = 39). The basic general information, past medical history, laboratory, and imaging examination data were collected and analyzed.

Results
In univariate analysis, there was no significant difference between the two groups in IL-6, PC, reaction time (R), alpha angle (Angle), maximum amplitude, or coagulation index (CI) (P > 0.05). TNF-α in the PVT group was significantly lower than that in the non-PVT group (P = 0.001). K-time (K) in the PVT group was significantly higher than that in the non-PVT group (P = 0.031). There was no significant difference in IL-6, TNF-α, PC, or TEG between different Child–Pugh classification groups (P > 0.05). There were no significant differences in TEG between the plasma transfusion group and the non-plasma transfusion group. In Binary logistic regression analysis, TNF-α (OR = 0.9881, 95%CI = 0.971, 0.990, P < 0.001), K(OR = 1.28, 95% = 1.053, 1.569, P = 0.014), activate partial thromboplastin time (APTT) (OR = 0.753, 95%CI = 0.656, 0.865, P < 0.001), portal vein diameter (OR = 1.310, 95%CI = 1.108, 1.549, P = 0.002)and the history of splenectomy or embolism (OR = 7.565, 95%CI = 1.514, 37.799, P = 0.014)were related to the formation of PVT.

Conclusions
TNF-α, K, APTT, portal vein diameter, and splenectomy or embolism history were associated with PVT formation, but IL-6 was not.
The burden of disease-specific multimorbidity among older adults in India and its states: evidence from LASI
Authors: Patel Priyanka , Muhammad T. , Sahoo Harihar 
Published: January 2023

Abstract
Background
Around the world, advances in public health and changes in clinical interventions have resulted in increased life expectancy. Multimorbidity is becoming more of an issue, particularly in countries where the population is rapidly ageing. We aimed to determine the prevalence of multimorbidity and disease-specific multimorbidity and examine its association with demographic and socioeconomic characteristics among older adults in India and its states.

Methods
The individual data from the longitudinal ageing study in India (LASI) were used for this study, with 11 common chronic conditions among older adults aged 60 and above years (N = 31,464). Descriptive statistics were used to report the overall prevalence of multimorbidity and disease-specific burden of multimorbidity. Multinomial logistic regression has been used to explore the factors associated with multimorbidity.

Results
Prevalence of single morbidity was 30.3%, and multimorbidity was 32.1% among older people in India. Multimorbidity was higher among females and in urban areas and increased with age and among those living alone. Hypertension, arthritis and thyroid were highly prevalent among females and chronic lung diseases and stroke were highly prevalent among males. The older people in the state of Kerala had a high prevalence of multimorbidity (59.2%). Multimorbidity was found to be more likely in older age groups of 75–79 years (RR-1.69; CI: 1.53–1.87) and 80 years and above (RR-1.40; CI: 1.27–1.56) and in the Western (RR-2.16; CI: 1.90–2.44) and Southern regions (RR-2.89; CI: 2.57–3.24). Those who were living with a spouse (RR-1.60; CI: 1.15–2.23) were more likely to have multimorbidity. Disease-specific multimorbidity was high in chronic heart disease (91%) and low in angina (64.8%).

Conclusions
The findings suggest that multimorbidity has a positive relationship with advancing age, and disease-specific burden of multimorbidity is higher among chronic heart patients. Comorbidity, especially among those who already have chronic heart disease, stroke, cholesterol or thyroid disorder can have severe consequences on physical functioning, therefore, disease-specific health management needs to be enhanced.
Classification of benign and malignant subtypes of breast cancer histopathology imaging using hybrid CNN-LSTM based transfer learning
Authors: Srikantamurthy Mahati Munikoti , Rallabandi V. P. Subramanyam , Dudekula Dawood Babu , Natarajan Sathishkumar , Park Junhyung 
Published: January 2023

Abstract
Background
Grading of cancer histopathology slides requires more pathologists and expert clinicians as well as it is time consuming to look manually into whole-slide images. Hence, an automated classification of histopathological breast cancer sub-type is useful for clinical diagnosis and therapeutic responses. Recent deep learning methods for medical image analysis suggest the utility of automated radiologic imaging classification for relating disease characteristics or diagnosis and patient stratification.

Methods
To develop a hybrid model using the convolutional neural network (CNN) and the long short-term memory recurrent neural network (LSTM RNN) to classify four benign and four malignant breast cancer subtypes. The proposed CNN-LSTM leveraging on ImageNet uses a transfer learning approach in classifying and predicting four subtypes of each. The proposed model was evaluated on the BreakHis dataset comprises 2480 benign and 5429 malignant cancer images acquired at magnifications of 40×, 100×, 200× and 400×.

Results
The proposed hybrid CNN-LSTM model was compared with the existing CNN models used for breast histopathological image classification such as VGG-16, ResNet50, and Inception models. All the models were built using three different optimizers such as adaptive moment estimator (Adam), root mean square propagation (RMSProp), and stochastic gradient descent (SGD) optimizers by varying numbers of epochs. From the results, we noticed that the Adam optimizer was the best optimizer with maximum accuracy and minimum model loss for both the training and validation sets. The proposed hybrid CNN-LSTM model showed the highest overall accuracy of 99% for binary classification of benign and malignant cancer, and, whereas, 92.5% for multi-class classifier of benign and malignant cancer subtypes, respectively.

Conclusion
To conclude, the proposed transfer learning approach outperformed the state-of-the-art machine and deep learning models in classifying benign and malignant cancer subtypes. The proposed method is feasible in classification of other cancers as well as diseases.
The optimal minimum lymph node count for carcinoembryonic antigen elevated colon cancer: a population-based study in the SEER set and External set
Authors: Zhang Hao , Wang Chunlin , Liu Yunxiao , Hu Hanqing , Tang Qingchao , Huang Rui , Wang Meng , Wang Guiyu 
Published: January 2023

AbstractPurposeThe aim of this paper was to clarify the optimal minimum number of lymph node for CEA-elevated (≥ 5 ng/ml) colon cancer patients.MethodsThirteen thousand two hundred thirty-nine patients from the SEER database and 238 patients from the Second Affiliated Hospital of Harbin Medical University (External set) were identified. For cancer-specific survival (CSS), Kaplan-Meier curves were drawn and data were analyzed using log-rank test. Using X-tile software, the optimal cut-off lymph node count was calculated by the maximal Chi-square value method. Cox regression model was applied to perform survival analysis.ResultsIn CEA-elevated colon cancer, 18 nodes were defined as the optimal minimum node. The number of lymph node examined (< 12, 12-17 and ≥ 18) was an independent prognosticator in both SEER set (HR12-17 nodes = 1.329,P <  0.001; HR< 12 nodes = 1.985,P <  0.001) and External set (HR12-17 nodes = 1.774,P <  0.032; HR< 12 nodes = 2.741,P <  0.006). Moreover, the revised 18-node standard could identify more positive lymph nodes compared with the 12-node standard in this population.ConclusionsWith the purpose of favorable long-term survival and accurate nodal stage for CEA-elevated colon cancer patients, the 18-node standard could be regarded as an alternative to the 12-node standard advocated by the ASCO and NCCN guidelines.
Global burden of prostate cancer attributable to smoking among males in 204 countries and territories, 1990–2019
Authors: Zhang Hanfei , Huang Dingping , Zhang Yingfeng , Wang Xia , Wu Jiangtao , Hong Daqing 
Published: January 2023

Abstract
Introduction
Understanding the latest global spatio-temporal pattern of prostate cancer burden attributable to smoking can help guide effective global health policy. This study aims to elucidate the trends in smoking-related prostate cancer from 1990 to 2019 using Global Burden of Disease (GBD) 2019 study data.

Methods
Data on prostate cancer attributable to smoking were extracted from Global Burden of Disease Study (GBD) 2019. The numbers and age-standardized rates on smoking-related prostate cancer mortality (ASMR) and disability-adjusted life years (ASDR) were analyzed by year, age, region, country, and socio-demographic index (SDI) level. Estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of ASMR and ASDR from 1990 to 2019.

Results
Of all prostate cancer deaths and DALYs globally in 2019, 6% and 6.6% were attributable to smoking, which contributed to 29,298 (95% CI 12,789 to 46,609) deaths and 571,590 (95% CI 253,490 to 917,820) disability-adjusted life-years (DALYs) in 2019. The number of smoking-related deaths and DALYs showed an upward trend, increasing by half from 1990 to 2019, while ASMR and ASDR declined in five sociodemographic indexes (SDI) regions, with the fastest decline in high SDI regions. For geographical regions, Western Europe and East Asia were the high-risk areas of prostate cancer deaths and DALYs attributable to smoking, among which China and the United States were the countries with the heaviest burden. The ASMR has decreased in all age groups, with the fastest decrease occurring in 75–79 years old. The ASMR or ASDR tended to increase in countries with the lowest SDI, but declined in countries with the highest SDI. The EAPC in ASMR or ASDR was highly negatively correlated with Human Development Index (HDI) in 2019, with coefficients 0.46.

Conclusion
The number of smoking-related prostate cancer deaths and DALYs continued to increase globally, whereas its ASMR and ASDR have been decreasing. This substantial progress is particularly significant in developed regions and vary across geographic regions. Medical strategies to prevent and reduce the burden should be adjusted and implemented based on country-specific disease prevalence.
Multi-omics analyses of CD276 in pan-cancer reveals its clinical prognostic value in glioblastoma and other major cancer types
Authors: Dai Lirui , Guo Xuyang , Xing Zhe , Tao Yiran , Liang Wulong , Shi Zimin , Hu Weihua , Zhou Shaolong , Wang Xinjun 
Published: January 2023

Abstract
Background
CD276 (also known as B7-H3) is one of the most important immune checkpoints of the CD28 and B7 superfamily, and its abnormal expression is closely associated with various types of cancer. It has been shown that CD276 is able to inhibit the function of T cells, and that this gene may potentially be a promising immunotherapy target for different types of cancer.

Methods
Since few systematic studies have been published on the role of CD276 in cancer to date, the present study has employed single-cell sequencing and bioinformatics methods to analyze the expression patterns, clinical significance, prognostic value, epigenetic alterations, DNA methylation level, tumor immune cell infiltration and immune functions of CD276 in different types of cancer. In order to analyze the potential underlying mechanism of CD276 in glioblastoma (GBM) to assess its prognostic value, the LinkedOmics database was used to explore the biological function and co-expression pattern of CD276 in GBM, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In addition, a simple validation of the above analyses was performed using reverse transcription-quantitative (RT-q)PCR assay.

Results
The results revealed that CD276 was highly expressed, and was often associated with poorer survival and prognosis, in the majority of different types of cancer. In addition, CD276 expression was found to be closely associated with T cell infiltration, immune checkpoint genes and immunoregulatory interactions between lymphoid and a non-lymphoid cell. It was also shown that the CD276 expression network exerts a wide influence on the immune activation of GBM. The expression of CD276 was found to be positively correlated with neutrophil-mediated immunity, although it was negatively correlated with the level of neurotransmitters, neurotransmitter transport and the regulation of neuropeptide signaling pathways in GBM. It is noteworthy that CD276 expression was found to be significantly higher in GBM compared with normal controls according to the RT-qPCR analysis, and the co-expression network, biological function and chemotherapeutic drug sensitivity of CD276 in GBM were further explored. In conclusion, the findings of the present study have revealed that CD276 is strongly expressed and associated with poor prognosis in most types of cancer, including GBM, and its expression is strongly associated with T-cell infiltration, immune checkpoint genes, and immunomodulatory interactions between lymphocytes and non-lymphoid cells.

Conclusions
Taken together, based on our systematic analysis, our findings have revealed important roles for CD276 in different types of cancers, especially GBM, and CD276 may potentially serve as a biomarker for cancer.
Novel cuproptosis-related long non-coding RNA signature to predict prognosis in prostate carcinoma
Authors: Cheng Xiaofeng , Zeng Zhenhao , Yang Heng , Chen Yujun , Liu Yifu , Zhou Xiaochen , Zhang Cheng , Wang Gongxian 
Published: January 2023

Abstract
Background
Cuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA) signature and the prognosis in prostate carcinoma remains elusive. This study aims to develop the novel cuproptosis-related lncRNA signature in prostate cancer and explore its latent molecular function.

Methods
RNA-seq data and clinical information were downloaded from the TCGA datasets. Then, cuproptosis-related gene was identified from the previous literature and further applied to screen the cuproptosis-related differentially expressed lncRNAs. Patients were randomly assigned to the training cohort or the validation cohort with a 1:1 ratio. Subsequently, the machine learning algorithms (Lasso and stepwise Cox (direction = both)) were used to construct a novel prognostic signature in the training cohorts, which was validated by the validation and the entire TCGA cohorts. The nomogram base on the lncRNA signature and several clinicopathological traits were constructed to predict the prognosis. Functional enrichment and immune analysis were performed to evaluate its potential mechanism. Furthermore, differences in the landscape of gene mutation, tumour mutational burden (TMB), microsatellite instability (MSI), drug sensitivity between both risk groups were also assessed to explicit their relationships.

Results
The cuproptosis-related lncRNA signature was constructed based on the differentially expressed cuproptosis-related lncRNAs, including AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1. Kaplan–Meier survival and ROC curves demonstrate that the prognosis signature as an independent risk indicator had excellent potential to predict the prognosis in prostate cancer. The signature was closely associated with age, T stage, N stage, and the Gleason score. Immune analysis shows that the high-risk group was in an immunosuppressive microenvironment. Additionally, the significant difference in landscape of gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity between both risk groups was observed.

Conclusions
A novel cuproptosis-related lncRNA signature was constructed using machine learning algorithms to predict the prognosis of prostate cancer. It was closely with associated with several common clinical traits, immune cell infiltration, immune-related functions, immune checkpoints, gene mutation, TMB, MSI, and the drug sensitivity, which may be useful to improve the clinical outcome.