bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Pathway Activities are Associated with Prognosis and Response to Bortezomib- containing Treatment in MCL1-M Based Molecular Subtypes of Multiple Myeloma
Authors: Yang Yuan , Jiang Sitao , Du Hang , Tang Jingling , Xiao Pengli , Wu Yin , Li Jiuyi , Feng Jing , Wei Yanfei , Samo Ayaz Ali , Lu Xuzhang , Fan Xiaolong 
Published: March 2024

Abstract

Multiple myeloma (MM) is the second most prevalent hematological malignancy and remains incurable with remarkable heterogeneity in prognosis and treatment response across the patients. Clinical diagnosis and the existing molecular classification systems are inadequate for predicting treatment responses. Based on the convergence between plasma cell development and MM pathogenesis, we identified a gene co-expression module centered on the plasma cell survival regulator MCL1 (MCL1 module, MCL1-M) in the transcriptomes of pre-treated MM, which enabled stratification of MM patients into MCL1-M high and MCL1-M low molecular subtypes with subtype-specific prognosis and response to Bortezomib-containing treatment. Here, we aimed to examine the mechanism underlying the disparate prognosis and treatment responses between the two molecular subtypes. Our findings reveal that MCL1-M high MM displays significant activation of pathways associated with cell proliferation, while MCL1-M low MM exhibits activation of immune-related signaling pathways. The relative enrichment of immune cells within the bone marrow microenvironment of MCL1-M low MM, particularity plasmacytoid dendritic cells, likely contributes to the activation of immune-related signaling pathways in this subset of myeloma cells. Using phase III trial data, we show that responses to Bortezomib-containing treatment is associated with the extent of unfolded protein response (UPR) signaling activity. Further, Bortezomib-mediated killing of MM cells could be enhanced or inhibited by in vitro manipulation of UPR activities in representative cell lines. In conclusion, MCL1-M based molecular subtypes of MM are characterized by distinct signaling activities from both malignant cells and bone marrow microenvironment, which may drive distinct prognosis and treatment responses.
Neoadjuvant treatment using chemotherapy and targeted therapy in a patient with resectable lung adenocarcinoma harboring BRAF V600E-mutation
Authors: Xiong Bingwan , Jiang Wenyang 
Published: March 2024

Abstract
In recent years, there has been significant progress in the treatment of non-small cell lung cancer (NSCLC). Besides conventional chemotherapy, targeted therapy and immunotherapy have demonstrated considerable efficacy in treating advanced NSCLC patients in both first and second-line settings. However, neoadjuvant therapy, as a promising therapeutic approach, requires further evaluation of its efficacy. Although targeted therapy for some common driver genes (EGFR, ALK) has been established as an effective treatment in the neoadjuvant setting, the efficacy of targeted therapy for other rare mutations remains uncertain. Within NSCLC, BRAF is one such rare driver gene and published data on the efficacy of neoadjuvant chemotherapy with targeted therapy for the BRAF V600E mutation in the treatment of advanced NSCLC is limited. Here, we report the first case successful neoadjuvant chemotherapy with targeted therapy followed by radical surgical excision in a patient with lung adenocarcinoma harboring the BRAF V600E mutation. The case informs us that chemotherapy with targeted therapy could be administered as a neoadjuvant strategy for selected cases of NSCLC harboring the BRAF V600E mutation.
CircRNA-0013747 induces mesangial cell proliferation in IgA nephropathy by targeting the Warburg effect via miR-330- 3p/PKM2 signaling
Authors: Zou Huimei , Chen Peilei , Deng Wenli , Liu Lu , Liu Miao , Xu Lifen , Xie Yin , Chen Min , Yu Jie , Luo Yingqin , Liu Xingmei , Liu Jun , Zhang Fan 
Published: March 2024

Abstract
Aberrant mesangial cell proliferation is a prevailing histopathological feature of immunoglobulin A nephropathy (IgAN) and is the primary driver of glomerular sclerosis and impaired renal function in IgAN patients. Prior research has revealed that PKM2-mediated aerobic glycolysis (the Warburg effect) frequently promotes mesangial cell growth and contributes to the development of various acute and chronic kidney diseases. However, the expression and functionality of PKM2 in IgA nephropathy, as well as the underlying molecular mechanisms governing its abnormal expression, remain elusive. Circular RNAs, a subset of noncoding RNAs, have garnered increasing attention due to mounting evidence of their pivotal roles in the initiation and progression of numerous disorders. The present study aimed to explore the effects of circRNA_0013747 on IgAN and the potential underlying mechanisms. The results indicated notable overexpression of circRNA_0013747 in lipopolysaccharide (LPS)-treated human mesangial cells (HMCs) and kidney biopsy samples from IgAN patients. CircRNA_0013747 was shown to facilitate mesangial cell proliferation and activate PKM2-mediated aerobic glycolysis, although these effects were mitigated by an increase in miR-330-3p. Mechanistically, circRNA_0013747 physically interacted with microRNA-330-3p (miR-330-3p) and hindered its function by directly binding to it. These findings imply that circRNA_0013747 can enhance glycolysis and proliferation in mesangial cells by modulating the miR-330-3p/PKM2 signaling pathway. In conclusion, the present results underscore the possibility of circRNA_0013747 serving as a promising therapeutic target for IgAN, suggesting new prospects for treating this disease.
Cytoskeletal gene alterations linked to sorafenib resistance in hepatocellular carcinoma
Authors: Hong Xiao , Chen Hangyu , Zhang Lei , Duolikun Maimaitiyasen , Zhen Baixin , Kuerban Subinuer , Li Xuehui , Wang Yuxi , Chen Long , Lin Jian 
Published: March 2024

Abstract
Background
Although sorafenib has been consistently used as a first-line treatment for advanced hepatocellular carcinoma (HCC), most patients will develop resistance, and the mechanism of resistance to sorafenib needs further study.
Methods
Using KAS-seq technology, we obtained the ssDNA profiles within the whole genome range of 7721 cells treated with sorafenib for differential analysis. We then intersected the differential genes obtained from the analysis of hepatocellular carcinoma patients in GSE109211 who were ineffective and effective with sorafenib treatment, constructed a PPI network, and obtained hub genes. We then analyzed the relationship between the expression of these genes and the prognosis of hepatocellular carcinoma patients.
Results
In this study, we identified 7 hub ERGs (ACTB, CFL1, ACTG1, ACTN1, WDR1, TAGLN2, HSPA8) related to drug resistance, and these genes are associated with the cytoskeleton.
Conclusions
The cytoskeleton is associated with sorafenib resistance in hepatocellular carcinoma. Using KAS-seq to analyze the early changes in tumor cells treated with drugs is feasible for studying the drug resistance of tumors, which provides reference significance for future research.
Heterogeneous expression of the atypical chemokine receptor ACKR3 in glioblastoma patient-derived tissue samples and cell cultures.
Authors: Isci Damla , Kuppens Amandine , Scalisi Joshua , Cokaiko Julie , D’Uonnolo Giulia , Wantz May , Szpakowska Martyna , Chevigné Andy , Rogister Bernard , Neirinckx Virginie 
Published: March 2024

Abstract
Background: Glioblastoma (GBM) is the most aggressive glial tumor of the adult brain, associated with invariably fatal outcome, and a deeper understanding of the underlying malignant mechanisms is necessary to address the current therapeutic failure. We previously demonstrated the role of the CXCL12/CXCR4 axis in GBM cell migration and resistance to ionizing radiation. The atypical receptor ACKR3, responsible for CXCL12 scavenging, was previously suggested as additional important player in the context of GBM.
Methods: Flow cytometry was used on GBM cell lines and patient-derived GBM cell cultures to quantify the level of ACKR3 expression. Moreover, we have at our disposal patient- derived formalin-fixed paraffin-embedded (FFPE) tissue, which is used for immunofluorescent analysis to characterize precisely ACKR3-positive cells. We used also an orthotopic xenograft model to study the impact of ACKR3 in vivo. Finally, qPCR analysis was also realized to study different gene expression on GBM cells.
Results: Following validation of our detection tools, we observed that ACKR3 is expressed within GBM patient tumor tissue, distributed in diverse cell types. In contrast to CXCR4, ACKR3 expression in patient-derived stem-like cells (GSCs) remains very low while ACKR3gene expression by tumor cells appears to be modulated by the in vivo environment. Using overexpression models, we also showed that in vitro ACKR3 had no significant effect on cell proliferation or invasion.
Conclusions: Altogether, these results suggest that ACKR3 plays a minor role in malignant GBM cells, although its expression is possibly regulated by in vivo influences. The subtle and multifaceted functions ACKR3 could exert in GBM should therefore only be tackled within a comprehensive tumor microenvironment considering tumoral but also non-tumoral cells.
Effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome: a randomized controlled trial
Authors: Wen Xinling , Li Fen , Yu Xuewen , Wang Li 
Published: March 2024

Abstract

Objective
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine and metabolic disease. The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters of PCOS women.
Methods
A total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment (4 weeks, 8 weeks and 12 weeks), including body mass index (BMI), waist to hip ratio (WHR), blood pressure, oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters.
Results
The serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (P < 0.05). In addition, with the extension of treatment time, the serum 25(OH)D concentration gradually increased. The BMI, WHR, insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in women of Vitamin D group after 12 weeks of treatment were significantly lower than that in women of control group (P < 0.05). Additionally, The serum insulin concentrations and HOMA-IR at different time points of OGTT, serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower than that in control group (obesity) (P < 0.05). The BMI, WHR, TG, TC and LDL-C concentration in women of vitamin D group (IR) were significantly lower compared with control group (IR) (P < 0.05). No significant difference was seen in metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity) (P > 0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) (P > 0.05).
Conclusion
The findings of this study supported that vitamin D supplementation had beneficial effects on metabolic parameters of PCOS women, especially in women with obesity or IR.
Effect of visceral fat on onset of metabolic syndrome
Authors: Bushita Hiroto , Ozato Naoki , Mori Kenta , Kawada Hiromitsu , Katsuragi Yoshihisa , Osaki Noriko , Mikami Tatsuya , Itoh Ken , Murashita Koichi , Nakaji Shigeyuki , Tamada Yoshinori 
Published: March 2024

Abstract
Background
Metabolic syndrome (MetS) increases the risk of cardiovascular and lifestyle-related diseases. Therefore, early detection is important to prevent MetS. This study analysed the effects of visceral fat on MetS using health examination. A MetS onset prediction algorithm was developed.
Methods
Health examination data were obtained from the Iwaki Health Promotion Project conducted in Aomori Prefecture in Japan, wherein labels indicated the development of MetS within the three years (213 onset and 1320 non-onset cases). The data were divided into training and test data (8:2 ratio), and 18 onset prediction models were developed to support the SHapley Additive exPlanations (SHAP) value. The onset labels and non-invasive input data were used as the output and input variables, respectively. We selected the model with the highest area under the curve (AUC) score when conducting five-fold cross validation, and the AUC of the test data was calculated. Feature impact was calculated based on SHAP.
Results
There were 169 and 1058 people in the metabolic and non-metabolic syndrome groups, respectively. The visceral fat area was significantly higher in the onset group than in the non-onset group (p < 0.00001). The cut-off value based on the receiver operating characteristic curve was 82 cm2, and the AUC was 0.86. Machine learning was employed on six items reported to contribute to the onset of MetS in addition to visceral fat to build an onset prediction algorithm. The cross-validation AUC = 0.90 and test AUC = 0.88 indicated a high-accuracy algorithm. The visceral fat was found to be the main factor, as confirmed by conventional feature importance in machine learning.
Conclusions
Visceral fat is crucial to determining the onset of MetS in the future. A high-accuracy onset prediction algorithm was developed based on non-invasive parameters, including visceral fat.
Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups
Authors: Holm Jonas Busk , Baggesen Emma , Cronin-Fenton Deirdre , Frystyk Jan , Bruun Jens Meldgaard , Christiansen Peer , Borgquist Signe 
Published: March 2024

Abstract

Purpose
Obesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI).
Methods
We assembled a cohort of women with BC (stage I-III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2,673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95%CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (BMI ≥ 30 kg/m2)).
Results
During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.24 mg/L) was associated with an increased risk of events (HRadj:1.58 [95%CI = 1.12–2.24]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HRadj:1.70 [95%CI = 1.09–2.66]; HRadj:1.75 [95%CI = 1.08–2.86]), but in obesity, the estimate was less precise (HRadj:1.73 [95%CI = 0.78–3.83]). For OS, high CRP was associated with increased risk of death (HRadj:2.47 [95%CI = 1.62–3.76]). The association was strong in normal-weight and overweight (HRadj:3.66 [95%CI = 1.95–6.87]; HRadj:1.92 [95%CI = 1.06–3.46]), but less clear in obesity (HRadj:1.40 [95%CI = 0.64–3.09]).
Conclusion
High CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.
Study on influence of laser processing parameters on thermal effects and surface morphology of GDL
Authors: Xie Xuan , Tang Changwu , Wang Changguo , Xu Sheng , Yin Bifeng 
Published: March 2024

Abstract

Traditional macroscopic structural design for proton exchange membrane fuel cells (PEMFC) has gradually become insufficient to meet the demands for improving fuel cell performance. Femtosecond laser processing is a promising solution capable of achieving precise control over the material structure and improving the quality of the processed material. In this study, femtosecond laser processing technology is used to modify the surface microstructure of gas diffusion layers (GDL) in PEMFC, aiming to enhance the characteristics of gas-liquid two-phase flow and electrochemical performance. In this paper, a novel coupled model based on the coupling of the two-temperature equation, phase transition and thermal stress is proposed. Comparison of the effects of different laser processing parameters on the surface morphology and thermal effects of carbon fibre materials. The impact of repetition rate on the heat-affected zone and pit quality is most significant. When rate increases from 100 kHz to 400 kHz, the heat-affected zone decreases from 42.8% to 29.3%. This process model can provide guidance and prediction for optimizing the laser processing parameters and improving the performance of the microporous structures.
GiMeFive: Towards Interpretable Facial Emotion Classification
Authors: Wang Jiawen , Kawka Leah 
Published: March 2024

Abstract
Deep convolutional neural networks have been shown to successfully recognize facial emotions for the past years in the realm of computer vision. However, the existing detection approaches are not always reliable or explainable, we here propose our model GiMeFive with interpretations, i.e., via layer activations and gradient-weighted class activation mapping. We compare against the state-of-the-art methods to classify the six facial emotions. Empirical results show that our model outperforms the previous methods in terms of accuracy on two Facial Emotion Recognition (FER) benchmarks and our aggregated FER GiMeFive. Furthermore, we explain our work in real-world image and video examples, as well as real-time live streams. Our code and supplementary material are available at https: //github.com/werywjw/SEP-CVDL.
Differential changes in the morphology and fuel loads of British obligatory and partial migrant passerines over half a century
Authors: Pickett Holly , Robinson Robert , Nudds Robert L. 
Published: March 2024

Abstract

Migratory distances and stop-over locations are changing for many passerines in response to climate change. Morphological changes have been linked to rising global temperatures in both migrants and residents, but the implications of these changes on fuel loads, and associated flight ranges are little studied. Wing length (lwing) and body mass (Mb) changes between 1964 and 2020 were calculated for 15 British migrant and partially migrant passerines. Changes in fuel load (Mf) and lean body mass (Mb−lean) were also estimated and used to predict flight ranges. Twelve of the species have undergone morphological and eight fuel load changes. Nine species were estimated to have reduced flight ranges, indicating that the morphological changes have not compensated fully for the reduction in flight range experienced since 1964. Partial migrants showed greater decreases in flight ranges than did full migrants, which may indicate greater behavioural plasticity in the former. Those species which do not adapt morphologically or behaviourally may be unable to complete long migrations, resulting in restriction to sub-optimal breeding/wintering habitats, or a need for more stops en route. This highlights the importance of conserving migratory stop-overs in the Mediterranean and north Africa.
Heat Removal from a Human Eye for Different Environmental Conditions - A CFD Study Using a Full-Scale Manikin
Authors: Feyli Farnaz , Yaghoubi Mahmood , Ahmadi Goodarz , Abouali Omid 
Published: March 2024

Abstract
The eye is an important organ of the human body, and its physiology can change mainly due to the ambient air temperature and velocity. In this study, a three-dimensional computational model for airflow around a full-scale manikin and the flow inside the eye is developed and used to evaluate the heat removal from the manikin eyes due to natural and forced convection under different environmental conditions. For natural convection, it was assumed that the movement of surrounding air was only due to the buoyancy effect in the body's thermal plume. Uniform air velocity and temperature far from the manikin were assumed for combined natural and forced convection. For simulating the velocity and temperature distribution, equations of continuity, momentum, energy, and turbulence transport model were solved numerically. The results for specific conditions were compared with the available experimental data reported in the literature and acceptable agreement was found. The validated computation model was used for several simulations of wind velocities and air temperatures. It was found that the eye surface temperature distribution predicted by the present model is closer to the experimental data than the earlier numerical studies for detached eyeballs using a constant convective heat transfer coefficient. The present results showed that the convective heat transfer coefficient over an eye surface depends strongly on the airflow velocity and temperature near the head.
The effects of radiotherapy and prognostic nomogram for pancreatic cancer patients with liver-only metastases
Authors: Liu Miaomiao , Yang Ping , Peng Jin , Zhou Fuxiang 
Published: March 2024

Abstract
Background: This study aimed to investigate the effect of radiotherapy on pancreatic cancer patients with liver metastasis only, and to establish a prognostic model.
Methods: Pancreatic cancer patients with liver-only metastases were obtained from 2010 to 2019 in the Surveillance, Epidemiology, and End Results (SEER) database. Then they were divided into a radiotherapy group and a non-radiotherapy group. Cancer-specific survival (CSS) before and after propensity score matching(PSM) was compared between the two groups. The radiotherapy group was then divided into training and validation cohorts. The prognostic nomogram for 6-, and 12-mouth CSS was constructed based on the training set. In addition, 38 patients were recruited from our hospital as an external validation set. The calibration curves, receiver operating characteristic (ROC) curve, Harrell’s concordance index (C-index), decision curve analysis (DCA), and Kaplan-Meier analysis based on risk stratification were performed to evaluate and verify this model.
Results: A total of 17453 patients with hepatic oligometastatic pancreatic cancer were included, of which 622 ( 3.6 % ) received radiotherapy and 16831 ( 96.4 % ) did not. Radiotherapy can significantly prolong survival time [median CSS: 8 months vs 5 months (HR, 0.716; 95%CI=0.655–0.783; p<0.001)]. After PSM, similar results can be obtained [median CSS: 8 months vs 7 months (HR, 0877; 95% CI=0.772–0.997; P=0.045)]. Independent prognostic factors in radiotherapy patients included age, race, histology, N staging, surgery, and chemotherapy. The ROC, C-index and Calibration curves showed good discrimination and calibration. DCA and KM curves further demonstrated the model's clinical applicability.
Conclusion: Radiotherapy significantly improves survival compared to non-radiotherapy. Patients younger than 70 years old, non-black, with no lymph node metastasis, primary tumor surgery, and systemic chemotherapy have better prognosis. Finally, we developed and validated a model for prognostication and patient counseling.