bluuebunny/crossref_metadata_2025_split huggingface dataset:
GAD1 contributes to the progression and drug resistance in castration resistant prostate cancer
Authors: Wan Lilin , Liu Yifan , Liu Ruiji , Mao Weipu 
Published: October 2023

Abstract
Background
Prostate cancer is currently the second most lethal malignancy in men worldwide due to metastasis and invasion in advanced stages. Studies have revealed that androgen deprivation therapy can induce stable remission in patients with advanced prostate cancer, although most patients will develop castration-resistant prostate cancer (CRPC) in 1–2 years. Docetaxel and enzalutamide improve survival in patients with CRPC, although only for a short time, eventually patients develop primary or secondary resistance, causing disease progression or biochemical relapse.

Methods
The gene expression profiles of docetaxel-sensitive or -resistant prostate cancer cell lines, namely GSE33455, GSE36135, GSE78201, GSE104935, and GSE143408, were sequentially analyzed for differentially expressed genes and progress-free interval significance. Subsequently, the overall survival significance and clinic-pathological features were analyzed by the R package. The implications of hub genes mutations, methylation in prostate cancer and the relationship with the tumor immune cell infiltration microenvironment were assessed with the help of cBioPortal, UALCAN and TISIDB web resources. Finally, effects of the hub genes on the progression and drug resistance in prostate cancer were explored using reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, cell phenotype, and drug sensitivity.

Result
Glutamate decarboxylase 1 (GAD1) was tentatively identified by bioinformatic analysis as an hub gene for the development of drug resistance, including docetaxel and enzalutamide, in prostate cancer. Additionally, GAD1 expression, mutation and methylation were significantly correlated with the clinicopathological features and the tumor immune microenvironment. RT-PCR, immunohistochemistry, cell phenotype and drug sensitivity experiments further demonstrated that GAD1 promoted prostate cancer progression and decreased the therapeutic effect of docetaxel or enzalutamide.

Conclusion
This research confirmed that GAD1 was a hub gene in the progression and development of drug resistance in prostate cancer. This helped to explain prostate cancer drug resistance and provides new immune-related therapeutic targets and biomarkers for it.
Rapid Mycobacterium abscessus antimicrobial susceptibility testing based on antibiotic treatment response mapping via Raman Microspectroscopy
Authors: Ren Weicong , Mao Yuli , Li Shanshan , Gao Bo , Fu Xiaoting , Liu Xiaolu , Zhu Pengfei , Shang Yuanyuan , Li Yuandong , Ma Bo , Sun Luyang , Xu Jian , Pang Yu 
Published: October 2023

Abstract
Objectives
Antimicrobial susceptibility tests (ASTs) are pivotal tools for detecting and combating infections caused by multidrug-resistant rapidly growing mycobacteria (RGM) but are time-consuming and labor-intensive.

Design
We used a Mycobacterium abscessus-based RGM model to develop a rapid (24-h) AST from the beginning of the strain culture, the Clinical Antimicrobials Susceptibility Test Ramanometry for RGM (CAST-R-RGM). The ASTs obtained for 21 clarithromycin (CLA)-treated and 18 linezolid (LZD)-treated RGM isolates.

Results
CAST-R-RGM employs D2O-probed Raman microspectroscopy to monitor RGM metabolic activity, while also revealing bacterial antimicrobial drug resistance mechanisms. The results of clarithromycin (CLA)-treated and linezolid (LZD)-treated RGM isolates exhibited 90% and 83% categorical agreement, respectively, with conventional AST results of the same isolates. Furthermore, comparisons of time- and concentration-dependent Raman results between CLA- and LZD-treated RGM strains revealed distinct metabolic profiles after 48-h and 72-h drug treatments, despite similar profiles obtained for both drugs after 24-h treatments.

Conclusions
Ultimately, the rapid, accurate, and low-cost CAST-R-RGM assay offers advantages over conventional culture-based ASTs that warrant its use as a tool for improving patient treatment outcomes and revealing bacterial drug resistance mechanisms.
Regulation of the integrin αVβ3- actin filaments axis in early osteogenic differentiation of human mesenchymal stem cells under cyclic tensile stress
Authors: Peng Yan , Qu Rongmei , Yang Yuchao , Fan Tingyu , Sun Bing , Khan Asmat Ullah , Wu Shutong , Liu Wenqing , Zhu Jinhui , Chen Junxin , Li Xiaoqing , Dai Jingxing , Ouyang Jun 
Published: October 2023

Abstract
Background
Integrins are closely related to mechanical conduction and play a crucial role in the osteogenesis of human mesenchymal stem cells. Here we wondered whether tensile stress could influence cell differentiation through integrin αVβ3.

Methods
We inhibited the function of integrin αVβ3 of human mesenchymal stem cells by treating with c(RGDyk). Using cytochalasin D and verteporfin to inhibit polymerization of microfilament and function of nuclear Yes-associated protein (YAP), respectively. For each application, mesenchymal stem cells were loaded by cyclic tensile stress of 10% at 0.5 Hz for 2 h daily. Mesenchymal stem cells were harvested on day 7 post-treatment. Western blotting and quantitative RT-PCR were used to detect the expression of alkaline phosphatase (ALP), RUNX2, β-actin, integrin αVβ3, talin-1, vinculin, FAK, and nuclear YAP. Immunofluorescence staining detected vinculin, actin filaments, and YAP nuclear localization.

Results
Cyclic tensile stress could increase the expression of ALP and RUNX2. Inhibition of integrin αVβ3 activation led to rearrangement of actin filaments and downregulated the expression of ALP, RUNX2 and promoted YAP nuclear localization. When microfilament polymerization was inhibited, ALP, RUNX2, and nuclear YAP nuclear localization decreased. Inhibition of YAP nuclear localization could reduce the expression of ALP and RUNX2.

Conclusions
Cyclic tensile stress promotes early osteogenesis of human mesenchymal stem cells via the integrin αVβ3-actin filaments axis. YAP nuclear localization participates in this process of human mesenchymal stem cells.
Indacaterol inhibits collective cell migration and IGDQ-mediated single cell migration in metastatic breast cancer MDA-MB-231 cells
Authors: Ayama-Canden Sophie , Tondo Rodolfo , Pineros Leyton Martha Liliana , Ninane Noëlle , Demazy Catherine , Dieu Marc , Fattaccioli Antoine , Sauvage Aude , Tabarrant Tijani , Lucas Stéphane , Bonifazi Davide , Michiels Carine 
Published: October 2023

SummaryMetastasis is the main cause of deaths related to breast cancer. This is particular the case for triple negative breast cancer. No targeted therapies are reported as efficient until now. The extracellular matrix, in particular the fibronectin type I motif IGDQ, plays a major role in regulating cell migration prior metastasis formation. This motif interacts with specific integrins inducing their activation and the migratory signal transduction.Here, we characterized the migratory phenotype of MDA-MB-231 cells, using functionalized IGDQ-exposing surfaces, and compared it to integrin A5 and integrin B3 knock-down cells. A multiomic analysis was developed that highlighted the splicing factor SRSF6 as a putative master regulator of cell migration and of integrin intracellular trafficking. Indacaterol-induced inhibition of SRSF6 provoked: i) the inhibition of collective and IGDQ-mediated cell migration and ii) ITGA5 sequestration into endosomes and lysosomes. Upon further studies, indacaterol may be a potential therapy to prevent cell migration and reduce metastasis formation in breast cancer.
The association of serum betaine concentrations with the risk of new-onset cancers: results from two independent nested case-control studies
Authors: Xie Hailun , Zhang Kangping , Wei Yaping , Ruan Guotian , Zhang Heyang , Li Shuqun , Song Yun , Chen Ping , Liu Lishun , Wang Binyan , Shi Hanping 
Published: October 2023

AbstractEvidence from epidemiologic studies on the association of circulating betaine levels with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective association of serum betaine concentrations with the risk of cancer. We performed two, nested, case-control studies utilizing data from the “H-type Hypertension Prevention and Control Public Service Project” (HHPCP) and the China Stroke Primary Prevention Trial (CSPPT), with 2782 participants (1391 cancer cases and 1391 matched controls) in the discovery cohort, and 228 participants (114 cancer cases and 114 matched controls) in the validation cohort. Odds ratios (OR) of the association between betaine and cancer were calculated using conditional logistic regression models. There was an association between serum betaine as a continuous variable and total cancer (OR = 1.03, 95%CI = 0.99–1.07, p = 0.097). Among cancer subtypes, a positive association was found between serum betaine and the risk of lung cancer, and an inverse association was found with other cancers. Interestingly, a U-shaped association was observed between serum betaine and digestive cancers, with a turning point of 5.01 mmol/L for betaine (betaine < 5.01 mmol/L, OR = 0.82, 95%CI = 0.59–1.14, p = 0.228; betaine ≥ 5.01 mmol/L, OR = 1.08, 95%CI = 1.01–1.17, p = 0.036). In the validation cohort, a significant association between serum betaine as a continuous variable and total cancer (OR = 1.48, 95%CI = 1.06–2.05, P = 0.020) was also found. High serum betaine was associated with increased risk of total cancer and lung cancer, and a U-shaped association was found with the risk of digestive cancers, with a turning point at about 5.01 mmol/L.
Polyploid cell dynamics and death before and after PEG-treatment of a NIH/3T3 derived culture: vinblastine effects on the regulation of cell subpopulations heterogeneity
Authors: Spano Alessandra , Sciola Luigi 
Published: October 2023

Abstract
Background
Neoplastic subpopulations can include polyploid cells that can be involved in tumor evolution and recurrence. Their origin can be traced back to the tumor microenvironment or chemotherapeutic treatment, which can alter cell division or favor cell fusion, generating multinucleated cells. Their progeny, frequently genetically unstable, can result in new aggressive and more resistant to chemotherapy subpopulations. In our work, we used NIHs cells, previously derived from the NIH/3T3 line after serum deprivation, that induced a polyploidization increase with the appearance of cells with DNA content ranging from 4 to 24c. This study aimed to analyze the cellular dynamics of NIHs culture subpopulations before and after treatment with the fusogenic agent polyethylene glycol (PEG), which allowed us to obtain new giant polyploid cells. Successively, PEG-untreated and PEG-treated cultures were incubated with the antimicrotubular poison vinblastine. The dynamics of appearance, decrease and loss of cell subpopulations were evaluated by correlating cell DNA content to mono-multinuclearity resulting from cell fusion and division process alteration and to the peculiarities of cell death events.

Results
DNA microfluorimetry and morphological techniques (phase contrast, fluorescence and TEM microscopies) indicated that PEG treatment induced a 4–24c cell increase and the appearance of new giant elements (64–140c DNA content). Ultrastructural analysis and autophagosomal–lysosomal compartment fluorochromization, which allowed us to correlate cytoplasmic changes to death events, indicated that cell depletion occurred through distinct mechanisms: apoptotic death involved 2c, 4c and 8c cells, while autophagic-like death involved intermediate 12–24c cells, showing nuclear (lobulation/micronucleation) and autophagic cytoplasm alterations. Death, spontaneously occurring, especially in intermediate-sized cells, was increased after vinblastine treatment. No evident cell loss by death events was detected in the 64–140c range.

Conclusions
PEG-treated NIHs cultures can represent a model of heterogeneous subpopulations originating from cell fusion and division process anomalies. Altogether, our results suggest that the different cell dynamics of NIHs subpopulations can affect the variability of responses to stimuli able to induce cell degeneration and death. Apoptptic, autophagic or hybrid forms of cell death can also depend on the DNA content and ability to progress through the cell cycle, which may influence the persistence and fate of polyploid cell descendants, also concerning chemotherapeutic agent action.
MiR-210 promotes bone formation in ovariectomized rats by regulating osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells through downregulation of EPHA2
Authors: Ren Lijue , Zhu Xiaohui , Tan Jiuting , Lv Xiangyu , Wang Jiahui , Hua Fei 
Published: October 2023

Abstract
Purpose
In osteoporosis, the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) is disrupted. The osteogenic differentiation of bone marrow MSCs (BMSCs) is important for improving osteoporosis. The aim of this study was to explore the role and molecular mechanism of miR-210 in the balance of osteogenic/adipogenic differentiation of BMSCs in postmenopausal osteoporosis.

Methods
Postmenopausal osteoporosis rat models were constructed by ovariectomy (OVX). BMSCs were isolated from the femur in rats of Sham and OVX groups. MiR-210 was overexpressed and suppressed by miR-210 mimics and inhibitor, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of miR-210, ephrin type-A receptor 2 (EPHA2), alkaline phosphatase (ALP), osterix (OSX), osteocalcin (Bglap), Runt-related transcription factor 2 (Runx2), peroxisome proliferator activated receptor gamma, and fatty acid binding protein 4 (FABP4) in each group of rat femoral tissues or BMSCs. Western blot was applied to detect the protein expression level of EPHA2 in rat femoral tissues and cells. Alizarin red S staining and oil red O staining were performed to assess the osteogenic and adipogenic differentiation of BMSCs, respectively. In addition, the targeting relationship between miR-210 and EPHA2 was verified by a dual luciferase gene reporter assay.

Results
The expression of miR-210 was significantly reduced in femoral tissues and BMSCs of OVX rats, and its low expression was associated with reduced bone formation. The osteogenic differentiation was enhanced in OVX rats treated with miR-210 mimic. Overexpression of miR-210 in transfected BMSCs was also found to significantly promote osteogenic differentiation and even inhibit adipogenic differentiation in BMSCs, while knockdown of miR-210 did the opposite. Further mechanistic studies showed that miR-210 could target and inhibit the expression of EPHA2 in BMSCs, thus promoting osteogenic differentiation and inhibiting adipogenic differentiation of BMSCs.

Conclusion
MiR-210 promotes osteogenic differentiation and inhibits adipogenic differentiation of BMSCs by down-regulating EPHA2 expression. As it plays an important role in the osteogenic/adipogenic differentiation of osteoporosis, miR-210 can serve as a potential miRNA biomarker for osteoporosis.
Development and evaluation of short-form version of the Constitution in Chinese Medicine Questionnaire: study a new and best brief instrument of Chinese medicine for health management
Authors: Bai Ming-Hua , Li Zhu-Qing , Wang Huai-Yu , Ma Xiao-Li , Wang Zhong-Li , Li Shi-Jun , Dong Si-Ying , Zhang Zi-Ling , Li Wen-Le , Chen Shun-Qi , Cai Yu-Yang , Zhao Xiao-Shan , Wang Ji , Wang Qi 
Published: October 2023

Abstract
Background
More efficient instruments for body constitution identification are needed for clinical practice. We aimed to develop the short-form version of the Constitution in Chinese Medicine Questionnaire (CCMQ) and evaluate for health management.

Methods
First, the short forms were developed through expert survey, classical test theory (CTT), and modern item response (IRT) based on the CCMQ. A combination of e-mail and manual methods was used in expert survey. Then, five indexes of CTT including criteria value-critical ratio, correlation coefficient, discrete tendency, internal consistency, and factor loading were used. And, IRT method was used through analyzing the discrimination and difficulty parameters of items. Second, the three top-ranked items of each constitution scale were selected for the simplified CCMQ, based on the three combined methods of different conditions and weights. Third, The psychometric properties such as completion time, validity (Construct, criterion, and divergent validity), and reliability (test–retest and internal consistency reliability) were evaluated. Finally, the diagnostic validity of the best short-form used receiver operating characteristic (ROC) curve.

Results
Three short-form editions were developed, and retained items 27, 23 and 27, which are named as WangQi nine body constitution questionnaire of Traditional Chinese Medicine (short-form) (SF-WQ9CCMQ)- A, B, and C, respectively. SF-WQ9CCMQ- A is showed the best psychometric property on Construct validity, Criterion validity, test–retest reliability and internal consistency reliability. The diagnostic validity indicated that the area under the ROC curve was 0.928 (95%CI: 0.924–0.932) for the Gentleness constitution scale, and were 0.895–0.969 and 0.911–0.981 for unbalance constitution scales using the cut-off value of the original CCMQ as 40 (“yes” standard) and 30 (“tendency” standard), respectively.

Conclusions
Our study successfully developed a well short-form which has good psychometric property, and excellent diagnostic validity consistent with the original. New and simplified instrument and opportunity are provided for body constitution identification, health management and primary care implementation.
MLKL regulates Cx43 ubiquitinational degradation and mediates neuronal necroptosis in ipsilateral thalamus after focal cortical infarction
Authors: Tang Yanyan , Chu Quanhong , Xie Guanfeng , Tan Yafu , Ye Ziming , Qin Chao 
Published: October 2023

AbstractNecroptosis is known to play an important role in the pathophysiology of cerebral ischemia; however, its role in the occurrence of secondary thalamic injury after focal cerebral infarction and the mechanism about how mixed lineage kinase domain-like (MLKL) executes necroptosis in this pathophysiology are still unclear. In this study, Sprague-Dawley rats were subjected to distal branch of middle cerebral artery occlusion (dMCAO). The expression of MLKL, connexin 43 (Cx43) and Von Hippel-Lindau (VHL) in vitro and in vivo were assessed by Western blot. Bioinformatic methods were used to predict the potential binding sites where MLKL interacted with Cx43, and the ubiquitination degradation of Cx43 regulated by VHL. The interactions among MLKL, Cx43, VHL, and Ubiquitin were assessed by immunoprecipitation. Dye uptake assay were used to examine the Cx43 hemichannels. Intracellular Ca2+ concentration was measured using Fluo-4 AM. Overexpression and site-directed mutagenesis studies were used to study the mechanisms by which MLKL regulates Cx43 ubiquitinational degradation to mediate neuronal necroptosis. We found that MLKL and Cx43 were upregulated in the ventral posterolateral nucleus (VPN) of the ipsilateral thalamus after dMCAO. In the in vitro experiments MLKL and Cx43 were upregulated after TSZ-mediated necroptosis in SH-SY5Y cells. The interaction between MLKL and Cx43 inhibited the K48-linked ubiquitination of Cx43 in necroptotic SH-SY5Y cells. VHL is an E3 ubiquitin ligase for Cx43, and MLKL competes with VHL for binding to Cx43. Interaction of MLKL Ser454 with Cx43 can trigger the opening of Cx43 hemichannels, causing increased intracellular Ca2+, and cell necroptosis. This innovative study at animal models, cellular, and molecular levels is anticipated to clarify the roles of MLKL and Cx43 in thalamic damage after focal cortical infarction. Our findings may help identify novel targets for neurological recovery after cortical infarction.
Translation and psychometric evaluation of the Spanish version of the problem areas in diabetes–pediatric version (PAID-Peds) survey
Authors: Casanovas-Marsal Josep-Oriol , Civitani Monzón Elisa , Ferrer Duce M. Pilar , Ferrer Lozano Marta , Vara Callau Marta , González de la Cuesta Delia , Yelmo Valverde Rosa , Pérez Repiso Victoria , Goicoechea Manterola Irune , de Arriba Muñoz Antonio 
Published: October 2023

Abstract
Background
Metabolic control and psychological management of paediatric type 1 diabetes mellitus (T1DM) can be challenging over time. Development of an instrument to assess the youth-reported burden could aid in preventing T1DM-associated diseases.

Methods
The aim of this study was to translate and validate the Spanish version of the Problem Area in Diabetes Survey–Pediatric version (PAID-Peds). A multicentre, cross-sectional translation and linguistic validation study was performed on a sample of 30 participants aged 8–17 years with a minimum 1-year history of T1DM diagnosed at the Miguel Servet University Hospital in Zaragoza (Aragon, Spain), Ramón y Cajal University Clinical Hospital in Madrid (Spain), and Sant Joan de Déu Hospital in Barcelona (Catalonia, Spain). The qualitative validation consisted of translation into Spanish and back-translation into English of the Paid-Peds survey and subsequent administration to the sample population. Data were gathered on parameters related to sociodemographic characteristics and metabolic control. Validity, feasibility, and test-retest reliability were evaluated. Internal consistency was determined using Cronbach’s alpha coefficient, test-retest reliability by means of interclass correlation, and paired samples using the Wilcoxon W-test. The study was approved by the ethics and research committees at each participating centre.

Results
The study assessed 30 children (46.7% female) with an average age of 13.33 ± 2.98 years; mean age at onset was 5.70 ± 3.62 years, and the mean disease duration was 7.63 ± 4.36 years. The mean score on the PAID-Peds survey was 42.88 ± 17.85. Cronbach’s alpha coefficient was 0.90. Test-retest reliability measured by interclass correlation coefficient was 0.8 (95% CI: 0.63–0.90). No significant differences in total scores were found between test and retest (Wilcoxon W-test: 289; p = 0.051).

Conclusions
The Spanish version of the PAID-Peds survey is a feasible, valid, and reliable instrument to assess the youth-perceived burden of T1DM.
Dedifferentiated endometrial carcinoma metastasis to axillary lymph node: a case report
Authors: Morrison Chase William , Sanjasaz Kayvon Nick , Nathanson Saul David , Raina-Hukku Supriya , Pinkney David Matthew , Davenport Alexis Anna 
Published: October 2023

Abstract
Background
We present an unusual case of a left axillary lymph node metastasis from a primary dedifferentiated endometrial carcinoma. This pattern of metastasis is likely the result of circulating tumor cells reaching the node through its arterial blood supply.

Case presentation
In this report, a 68-year-old white woman with a dedifferentiated endometrial carcinoma underwent a hysterectomy. She later developed an enlarged axillary lymph node due to metastatic dedifferentiated endometrial carcinoma, treated with chemotherapy and anti-programmed cell death protein 1 immunotherapy resulting in a complete clinical and radiological response.

Conclusion
A review of the literature reveals the rarity of blood-borne lymph node metastasis, especially with uterine carcinoma. Immunotherapy has shown promising results in the treatment of some subtypes of metastatic uterine carcinoma.