bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rapid therapeutic drug monitoring method of carbamazepine in serum by using coffee ring effect-based surface-enhanced Raman spectroscopy
Authors: Zhu Qingxia , Li Xinhang , Li Dan , Lu Feng , Zhao Yunli , Yuan Yongfang 
Published: October 2022

Abstract
Carbamazepine (CBZ) has a narrow therapeutic concentration range, and therapeutic drug monitoring (TDM) is necessary for its safe and effective administration. This study aims to develop a procedure for CBZ detection in plasma using coffee ring effect-based surface-enhanced Raman spectroscopy (SERS). Silver nanoparticles deposited onto silicon wafers were used as the SERS-active material. Surface treatment optimization of the silicon wafers and the liquid–liquid extraction method were conducted to eliminate the influence of impurities on the silicon wafer surface and the protein matrix. The proposed detection procedure allows for the fast determination of CBZ in artificially spiked serum samples within a concentration range of 2.5–40 μg·mL–1, which matches the range of the drug concentrations in the serum after oral medication. The limit of detection for CBZ was found to be 0.01 μg·mL–1. The developed method allowed CBZ and its metabolites to be ultimately distinguished from real serum samples. It is anticipated that the developed method will have great potential for monitoring other drug concentrations.
Antemortem Domain-Specific Cognitive Functions Predict Postmortem Neuropathological Traits in the Framingham Heart Study
Authors: Li Donghe , Wang Yuehting , Ang Ting F.A. , Xia Weiming , Aytan Nurgul , Mez Jesse , Devine Sherral , Au Rhoda , Farrer Lindsay A. , Stein Thor D. , Jun Gyungah 
Published: October 2022

Abstract
Background: Clinical diagnosis of Alzheimer’s disease is aided by neuropsychological (NP) tests. However, correlations between antemortem domain specific cognitive functions from NP tests and neuropathological outcomes at autopsy are not well known.
Methods: We conducted association tests between antemortem NP tests and postmortem neuropathological traits in 159 participants from the Framingham Heart Study (FHS). The NP tests included memory, language, executive, and visuospatial domains. Neuropathological traits contained neuropathological diagnosis of AD (AD), Braak stage, neuritic plaque score, and quantitative measures of site-specific tau phosphorylation (pTau), density of microglia and synaptic protein density from the dorsolateral prefrontal cortex area of the autopsied brains in the FHS subjects. For the most significantly associated postmortem outcome (pTau) with antemortem cognitive domains, we compared prediction models containing significant cognitive domains with those including all cognitive domains, adjusting for interval age and APOE ɛ4 status as covariates.
Results: We identified significant associations for AD pathology with memory, language, and executive domains (best P with memory=1.1x10-4). At least three distinct cognitive domains were nominally associated (P<0.05) with Braak stages, plaque scores, and phosphorylated paired helical filament tau (AT8). Language domain impairment was associated with microglia (Iba1) density, while language and executive function impairments were significantly associated with complement component C4a and C4b levels, respectively (P<0.05). Impairment in the memory domain was significantly associated with levels of pTau181, pTau202, pTau231, postsynaptic density protein 95 (PSD95), and ratio of Aβ42/40 (best P with pTau231=0.008). Impairment in the visuospatial domain was associated with pTau396, and the area under the curve (AUC) for a model predicting high pTau396 utilizing the block design was better (AUC=0.81, 95% confidence interval [CI]: 0.46-0.85) than for a model including tests for all domains (AUC=0.61, 95% CI=0.31-0.84).
Conclusions: These findings confirm significant associations between antemortem domain specific cognitive tests and neuropathological traits at autopsy, especially postmortem measures of phosphorylated tau levels. Prediction models demonstrated that impairment in block design alone is sufficient to predict a high-level of pTau396 at autopsy.
Automatic tool for analysis of morphometric changes in the tumor spheroids regions treated with cisplatin
Authors: Fonseca-Benitez Angela , Casallas Luz Helena Camargo , Guarnizo-Mendez Hector , Perdomo-Lara Sandra Janneth 
Published: October 2022

Abstract
Spheroids provides an in vitro cell culture model that mimics cancer cell growth in the in vivo solid tumor microenvironment. This cell culture model has revolutionized drug response studies. The architecture of the spheroid allows the cells to form different layers depending on oxygen, nutrients, and pH gradients. These layers, called proliferative, quiescent, and necrotic zones, are relevant in the treatment response evaluation because the cells present there have different behavior, which provides a better approach to evaluate treatments that can be correlated to in vivo response. Consequently, a key aspect for evaluation in this culture type is to analyze its morphology features; this is added to the main problem in extracting all parameters necessary for analysis. To overcome this difficulty, in this work, we proposed a MATLAB script for analyzing layers or zones of CAL27 spheroids with automatic computation of different morphological parameters. We correlated with in vitro experiments to improve the development and evaluation of antitumor drugs. This analysis utilizes inverted microscopy imaging of squamous oral carcinoma cells growing in spheroids treated or untreated with cisplatin. We developed and tested a software tool that detects each zone of the spheroid from threshold values and the changes in treatment response. The morphological parameters sphericity and solidity changes were observed in spheroids treated and untreated with cisplatin 20µM in the different zones. Besides, we observed that the quiescent zone was increased after treatment.
The overexpression and clinical significance of TBX15 in human gliomas
Authors: Yan Dongming , Yu Yaping , Ni Qiongwei , Meng Qingwen , Wu Haolin , Ding Shun , Liu Xiaoqian , Tang Caiying , Liu Qibing , Yang Kun 
Published: October 2022

Abstract
T-box transcription factor 15 (TBX15) is upregulated in a variety of tumors and has been reported to promote uncontrolled proliferation of tumor cells and induce tumor cells to avoid apoptosis, thus accelerating the malignant transformation of malignant tumors. However, the prognostic value of TBX15 in glioma and its relationship with immune infiltration remain unknown. In this study, we intended to explore the prognostic value of TBX15 and its link to glioma immune infiltration and examine TBX15 expression in pan-cancer using RNAseq data in TPM format from TCGA and GTEx. TBX15 mRNA and protein expressions in glioma cells and adjacent normal tissue were detected and compared by RT-qPCR and Western blot. The effect of TBX15 on survival was assessed by Kaplan-Meier Method. The correlation between TBX15 upregulation and the clinicopathological characteristics of glioma patients was assessed by using CGGA and TCGA databases, and the relationship between TBX15 and other genes in glioma was evaluated by using TCGA data. The top 300 genes most significantly associated with TBX15 were selected to establish a PPI network through the STRING database. The relationship between TBX15 mRNA expression and immune cell infiltration was explored by using ssGSEA and the TIMER Database. It was found that TBX15 mRNA expression in glioma tissues was significantly higher than that in the adjacent normal tissues, and this difference was most obvious in high-grade gliomas. TBX15 expression was increased in human gliomas and associated with worse clinicopathological characteristics and poorer survival prognosis in glioma patients. In addition, elevated TBX15 expression was linked to a collection of genes involved in immunosuppression. In conclusion, TBX15 played an important role in immune cell infiltration in glioma and may prove to be a predictor of the prognosis in glioma patients.
Prediction of surgical outcome by tumor volume doubling time via stereo imaging software in early non-small cell lung cancer
Authors: Liu Chia-Chi , Cheng Ya-Fu , Ke Pei-Cing , Chen Yi-Ling , Lin Ching-Min , Wang Bing‑Yen 
Published: October 2022

Abstract
Background:
Volume doubling time (VDT) has been proven to be a powerful predictor of lung cancer progression. In non-small cell lung cancer (NSCLC) patients receiving sublobar resection, the discussion of correlation between VDT and surgery was absent. We propose to investigate the surgical outcomes according to VDT, to see if it could serve as a prognostic predictor preoperatively.
Methods:
We retrospectively studied 96 NSCLC patients post sublobar resection from 2012 to 2018, collecting two chest CT scans preoperatively of each case and calculating VDT. The receiver operating characteristic curve was constructed to identify the optimal cut-off point of VDTs as 133 days. We divided patients into two groups: VDT < 133 days (n=22) and VDT ≥ 133 days (n=74). Univariable and multivariable analyses were performed for comparative purposes.
Results:
Clinical characteristics including gender, smoking history, chronic obstructive pulmonary disease, epidermal growth factor receptor gene mutation, tumor stage, and histological type were significantly different between the two groups. Univariable and multivariable analyses revealed that the consolidation and tumor diameter ratio was the factor of overall survival (OS), and VDT was the only factor of disease-free survival (DFS). The 5-year OS rates of patients with VDTs ≥ 133 days and VDTs < 133 days, respectively, were 89.9% and 71.9% (p = 0.003), and the 5-year DFS rates were 95.9% and 61.5% (p = 0.002).
Conclusions:
As the VDT serves as a powerful prognostic predictor and provides an essential role in planning surgical procedures, the evaluation of VDT preoperatively is highly suggested.
Increase of fibrosis-related genes in doxorubicin-induced senescent human dermal fibroblasts but their secretome does not trigger a paracrine fibrotic response in non-senescent cells
Authors: Nosrati Fariba , Grillari Johannes , Azarnia Mahnaz , Nabiuni Mohammad , Moghadasali Reza , Karimzadeh Latifeh , lammermann Ingo 
Published: October 2022

Abstract
Tissue fibrosis is associated with the aging process of most of our organs, and organ aging correlates with the chronic accumulation of senescent cells. Fibrosis occurs when fibroblasts proliferate and deposit pathological amounts of extracellular matrix (ECM), leading to progressive tissue scarring and organ dysfunction. Fibroblasts play a key role in fibrosis, especially in the skin where fibroblasts are the most abundant cell type in the dermis and are mainly responsible for the synthesis of ECM. This study aims to investigate how senescent fibroblasts and their secretome influence dermal fibrosis. Here we used human dermal fibroblasts (HDFs) treated with doxorubicin (doxo) to induce senescence. The senescent phenotype of these stress-induced premature senescent (SIPS) cells was confirmed with several markers. The expression of pro-fibrotic genes was quantified and finally, the impact of their secretome on the fibrotic response of non-senescent fibroblasts was assessed. Doxorubicin treatment, induced senescence in fibroblasts which has been confirmed with elevated senescence-associated β- galactosidase (SA-β-gal) activity, absence of BrdU incorporation, upregulation of p21, and loss of Lamin b1. Expression levels of the pro-fibrotic genes ACTA2 and FN1 increased in SIPS cells, but in contrast to studies using lung fibroblasts the secretome of these cells failed to induce a paracrine fibrotic response in non-senescent cells. In general, these results suggest that these senescent cells are potentially profibrotic, and their accumulation can trigger fibrosis in organs.
Analysis and occurrence of organophosphorus flame retardants and their metabolites in animal derived food
Authors: Li Yuanwei , Li Jinyang , Fu Xiaojiao 
Published: October 2022

Abstract
An optimized QuEChERS method for simultaneous extraction of 11 OPFRs and 7 mOPFRs in animal derived food was established and analyzed by UHPLC-MS/MS. Briefly, for beef, 4% FA/ACN was used as the extractant and Captiva EMR-Lipid was used to purify the substrate. For fish, 40% MeOH/CAN was used for extraction, followed by 200 mg PSA for purification to achieve the effective extraction of the target compounds. The method has been verified in terms of accuracy and precision. The recoveries of the method were 70%-120%, and the relative standard deviation were less than 20%. This validated method was successfully applied to determine the concentrations of the OPFRs and mOPFRs in animal derived food. The results indicated that TMP and TPrP were below the LODs in all the samples, and the remaining targets were detected to varying degrees. TCEP、TCIPP and BCEP were the primary pollutants in the fish and shrimp, indicating the transformability of OPFRs and mOPFRs. Based on the current research, exposure to OPFRs and mOPFRs through food consumption are safe to human body. However, long term exposure to OPFRs and mOPFRs still needs further study.
Effect of ouabain on glutamate transport in the hippocampus of rats with LPS-induced neuroinflammation
Authors: Garcia Israel José Pereira , Kinoshita Paula Fernanda , Valadares Jéssica Martins Moura , Carvalho Luciana Estefani Drumond , Scavone Cristoforo , Cortes Vanessa Faria , Barbosa Leandro Augusto , Santos Hérica Lima 
Published: October 2022

Abstract
A lipopolysaccharide (LPS)-induced neuroinflammation rat model was used to study the effects of ouabain (OUA) at low concentrations, which can interact with the Na, K-ATPase, causing the modulation of intracellular signalling pathways in the central nervous system. Our study aimed to analyse the effects of OUA on glutamate transport in the hippocampus of rats with LPS-induced neuroinflammation. Adult male Wistar rats were divided into four groups: OUA (1.8 µg/kg), saline (CTR), LPS (200 µg/kg), and OUA + LPS (OUA 20 min before LPS). The animals were sacrificed after 2 h, and the hippocampus was collected for analysis. After treatment, we determined the activities of Na, K-ATPase and glutamine synthetase (GS). In addition, expression of the α1, α2, and α3 isoforms of Na, K-ATPase and the glutamate transporters, EAAT1 and EAAT2, were also analysed. Analysis of the expression of the α-isoform of the Na, K-ATPase revealed that treatment with OUA caused an increase in α2 isoform expression (~ 20%), whereas LPS decreased its expression (~ 22%), and the OUA pre-treatment prevented the deleterious effect of LPS. Moreover, LPS caused a decrease of approximately 50% in GS activity compared to that in the CTR group; however, OUA pre-treatment attenuated the LPS effect. Notably, it was found that treatment with OUA caused an increase in the expression of EAAT1 (~ 30%) and EAAT2 (~ 25%), whereas LPS caused a decrease in the expression of EAAT1 (~ 23%) and EAAT2 (~ 25%) compared to that in the CTR group. However, OUA pre-treatment abrogated the effect of LPS. OUA also interacts with FXYD2 and glutamate transporters. Our data suggest a neuroprotective effect of OUA against LPS-induced injury in the rat hippocampus.
Stay here, but keep quiet: the effects of anthropogenic noise on Guiana dolphins (Sotalia guianensis) in Southeastern Brazil.
Authors: Maciel Israel , Belderrain Teresa , Alves Maria Alice Santos , Tardin Rodrigo 
Published: October 2022

Abstract
Shipping is the principal source of anthropogenic noise in the aquatic soundscape of coastal areas. Noise can have temporary or permanent effects on the physiology, behavior, and ecology of the marine mammals and, as noise pollution is considered to be an important threat to Guiana dolphins (Sotalia guianensis), we focused on this question in the present study. We modeled the impacts of anthropogenic noise on the acoustic behavior and distribution of these dolphins. We considered the acoustic parameters and occurrence of Guiana dolphins as the response variables and Sound Exposure Levels (SEL) and environmental factors as the explanatory variables. The dolphins used noisier areas but communicated mainly in less noisy areas, given that anthropogenic noise levels induced a reduction in whistle rates. Although the dolphins did not appear to avoid the noisiest areas, their communication was impaired, and there may be areas in which communication is impracticable in this species.
Slc11a1 gene polymorphism influences dextran sulfate sodium (DSS)-induced colitis in a murine model of acute inflammation
Authors: Andrade Stephane Tereza , Guidugli Tamiris , Rodrigues Bridilla Luiza , Fernandes Natalia Coelho , Guerra Juliana , Borrego Andrea , de Souza Jean Gabriel , Starobinas Nancy , Jensen Jose , Cabrera Wafa , De Franco Marcelo , Ibañez Olga , Massa Solange , Ribeiro Orlando 
Published: October 2022

Abstract
Ulcerative Colitis (UC) is an inflammatory disease characterized by colonic mucosal lesions associated with an increased risk of carcinogenesis. UC pathogenesis involves environmental and genetic factors. Genetic studies have indicated the association of gene variants coding for the divalent metal ion transporter SLC11A1 protein (formerly NRAMP1) with UC susceptibility in several animal species. Two mouse lines were genetically selected for high (AIRmax) or low (AIRmin) acute inflammatory responses (AIR). AIRmax is susceptible, and AIRmin is resistant to DSS-induced colitis and colon carcinogenesis. Furthermore, AIRmin mice present polymorphism of the Slc11a1 gene. Here we investigated the possible modulating effect of the Slc11a1 R and S variants in DSS-induced colitis by using AIRmin mice homozygous for Slc11a1 R (AIRminRR) or S (AIRminSS) alleles. We evaluated UC by the disease activity index (DAI), considering weight loss, diarrhea, blood in the anus or feces, cytokines, histopathology, and cell populations in the distal colon epithelium. AIRminSS mice have become susceptible to DSS effects, with higher DAI, IL6, G-CSF, and MCP-1 production and morphological and colon histopathological alterations than AIRminRR mice. The results point to a role of the Slc11a1 S allele in UC induction in the genetic background of AIRmin mice.
Exploring the lymph node’s microenvironment for personalized management of Luminal A breast cancer
Authors: Gante Inês , Ribeiro Joana Martins , Mendes João , Gomes Ana , Almeida Vânia , Regateiro Frederico S. , Caramelo Francisco , Silva Henriqueta Coimbra , Dias Margarida Figueiredo 
Published: October 2022

Abstract
Background
Lymph nodes (LNs) are the main doorway for tumor cell metastases from the primary site and its evaluation is a major prognostic factor. The One Step Nucleic Acid Amplification (OSNA) is being adopted worldwide for sentinel-LNs (SLNs) staging in breast cancer (BC). SLNs´ OSNA lysate may be used for gene expression studies, being the potentially ideal samples to search for new markers related to immune response. Using a targeted gene expression approach, we aim to identify transcriptomic patterns of SLNs immune response and biomarkers that may improve risk stratification and personalized therapy for patients with Luminal A BC.
Methods
This was an observational, prospective, pilot study that included 32 patients with Luminal A early-stage BC: 16 patients with OSNA negative SLNs and 16 patients with OSNA positive SLNs. After the OSNA assay, rather than being discarded, the remaining OSNA lysates were prepared for target RNA sequencing (RNA-seq) analysis, using the Oncomine™ Immune Response Research Assay. Identification of differentially expressed genes (DEGs) for group comparisons was performed by DESeq2 R package (version 1.36.0) in R (version 4.2.0). Data analysis was performed using STATA software, version 13.1, and statistical significance was set at p < 0.05.
Results
In Luminal A BC patients, several genes were upregulated in metastatic SLNs, including KRT7, VTCN1, CD44, GATA3, ALOX15B, RORC and NECTIN2. In macrometastatic SLNs, LRG1, CD276, FOXM1 and IGF1R were also upregulated. In metastatic SLNs, higher values of total tumor load (TTL) correlated with a higher expression of most DEGs. Hierarchical clustering analysis revealed three different clusters, not coincident with pN0, pN1mi and pN1 classification.
Conclusions
A better understanding of the complex interplay between cancer cells and host immunity is essential for the choice of personalized treatments in Luminal A BC. The identified DEGs codify proteins mainly involved in cancer aggressiveness and with impact in immune response. These DEGs may improve prognosis accuracy and increase the efficacy and safety of targeted therapies in Luminal A BC patients. As OSNA assay is being implemented for SLNs staging in other cancers, RNA-seq in the OSNA lysate could also have a wider utility.
TSH Level as a Risk Factor for Thyroid Malignancy in Euthyroid Nodules
Authors: Alaraifi Abdulaziz K , Alessa Mohammed , Hijazi Leen O , Alayed Areej M , Alsalem Abdulaziz A 
Published: October 2022

Abstract
Objective
With the increased prevalence of incidental thyroid cancer, determining the predictors of thyroid malignancy has become a source of debate. This study aimed to determine the impact of Thyroid Stimulating Hormone (TSH) levels on thyroid cancer incidence in euthyroid nodules.
Methods
A retrospective study included 421 patients who underwent thyroidectomy at a tertiary hospital between 2016 and 2020. Patients' demographics, history of cancer, preoperative workup, and final histology reports were obtained. The study sample was divided into two groups based on the final histopathology (benign vs. malignant). The two groups were compared using the appropriate statistical tests to determine the predictors of thyroid cancer in euthyroid nodules.
Results
TSH level was significantly higher in malignant nodules compared to benign nodules (1.94 vs. 1.62, p = 0.002). It was 1.54 times more likely for thyroid nodules to be malignant when TSH levels were higher (p = 0.038). Meanwhile, larger nodules (> 4 cm) were significantly more prevalent in benign nodules (43.1%) than in malignant nodules (21.1%). Larger nodules decreased the possibility of thyroid cancer by 24% (OR = 0.760, p-value 0.004).
Conclusion
High TSH levels in euthyroid nodules were significantly correlated with the risk of thyroid malignancy. In addition, as Bethesda category proceeded toward malignancy, TSH levels increased. High TSH levels and small nodule sizes can be used as additional parameters in predicting thyroid cancer in euthyroid nodules.
Patient Management With Severe Maxillofacial Infection in Tertiary Hospitals: a Multidisciplinary Treatment Algorithm
Authors: Vergetti Francisco de Assis Crescêncio , Filho Josfran da Silva Ferreira , Gondim Ricardo Franklin , Junior José Maria Sampaio Menezes , Lima Daniel Souza , Silva Paulo Goberlânio de Barros , Carvalho Abrahão Cavalcante Gomes Souza 
Published: October 2022

Abstract
Background: The general objective of this study was to evaluate the management of patients with severe maxillofacial infections in a tertiary care hospital.
Methods: A study was performed whose methodology consisted of evaluating the epidemiological profile of 35 patients with serious maxillofacial infections, including age group, and gender. The patients were evaluated between December 2020 and November 2021. A total of 35 patients (18 male and 17 female) were recorded in this study.
Results: The most frequent etiological factor leading to infection was dental (91.4%), followed by infected fractures (5.7%). The teeth most frequently involved were the lower third and other lower molars (1st, 2nd, and premolars). The most performed treatment (14 patients) was drainage of the infected space, removal of the etiological agent and intravenous antibiotic therapy. 10 patients (8.6%) were treated with incision, drainage, and antibiotic IV therapy..
Conclusions: Multidisciplinary management can decrease morbidity and mortality in patients with severe maxillofacial infections.