bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse associations between maternal deoxynivalenol exposure and birth outcomes: a prospective cohort study in China
Authors: Tan Tianqi , Chen Tingting , Zhu Wenwen , Gong Lin , Yan Yizhong , Li Qian , Chen Li , Li Yiling , Liu Jialin , Li Yanan , Yang Xuefeng , Hao Liping , Wang Huaiji , Yang Nianhong , Wei Sheng 
Published: August 2023

Abstract
Background
Deoxynivalenol (DON), one of the most prevalent mycotoxins, has been found to cause fetal growth retardation in animals. However, limited evidence exists regarding its effects on pregnant women.

Methods
Maternal urinary concentration of total DON (tDON) and free DON (fDON) in the second trimester was measured using liquid chromatography with tandem mass spectrometry. Provisional daily intake (PDI) of DON was calculated based on tDON concentration. Linear and logistic regression models were used to evaluate the association between DON exposure levels and birth weight, birth length, and the risk of small for gestational age (SGA).

Results
Among 1538 subjects, the median concentrations of tDON and fDON were 12.1 ng/mL and 5.1 ng/mL, respectively. The PDI values revealed that the median DON intake was 0.7 µg/kg bw, and 35.9% of the total population exceeded the provisional maximum tolerable daily intake (PMTDI) of 1 µg/kg bw. Compared with the lowest tertile, birth weight decreased by 81.11 g (95% CI: -127.00, -35.23) for tDON (P-trend < 0.001) and 63.02 g (95% CI: -108.72, -17.32) for fDON (P-trend = 0.004) in the highest tertile. Each unit increase in Ln-tDON and Ln-fDON was also inversely associated with birth weight. Furthermore, compared to those who did not exceed PMTDI, pregnant women whose PDI exceeded PMTDI had lower birth weight (β = -79.79 g; 95% CI: -119.09, -40.49) and birth length (β = -0.21 cm; 95% CI: -0.34, -0.07), and a higher risk of SGA (OR = 1.48; 95% CI: 1.02, 2.15) in their offspring. Similar associations with birth weight, birth length, and SGA were found when comparing the highest tertile of PDI to the lowest tertile (all P-trend < 0.05).

Conclusions
Maternal DON exposure is related to decreased birth weight. Our findings implicate that DON exposure during pregnancy may cause fetal growth faltering, and measures should be taken to reduce DON exposure in pregnant women.
Targeted delivery of a PD-1-blocking scFv by CD133-specific CAR-T cells using nonviral Sleeping Beauty transposition shows enhanced antitumour efficacy for advanced hepatocellular carcinoma
Authors: Yang Chaopin , You Jinqi , Pan Qiuzhong , Tang Yan , Cai Liming , Huang Yue , Gu Jiamei , Wang Yizhi , Yang Xinyi , Du Yufei , Ouyang Dijun , Chen Hao , Zhong Haoran , Li Yongqiang , Yang Jieying , Han Yulong , Sun Fengze , Chen Yuanyuan , Wang Qijing , Weng Desheng , Liu Zhongqiu , Xiang Tong , Xia Jianchuan 
Published: August 2023

Abstract
Background
CD133 is considered a marker for cancer stem cells (CSCs) in several types of tumours, including hepatocellular carcinoma (HCC). Chimeric antigen receptor-specific T (CAR-T) cells targeting CD133-positive CSCs have emerged as a tool for the clinical treatment of HCC, but immunogenicity, the high cost of clinical-grade recombinant viral vectors and potential insertional mutagenesis limit their clinical application.

Methods
CD133-specific CAR-T cells secreting PD-1 blocking scFv (CD133 CAR-T and PD-1 s cells) were constructed using a sleeping beauty transposon system from minicircle technology, and the antitumour efficacy of CD133 CAR-T and PD-1 s cells was analysed in vitro and in vivo.

Results
A univariate analysis showed that CD133 expression in male patients at the late stage (II and III) was significantly associated with worse progression-free survival (PFS) (P = 0.0057) and overall survival (OS) (P = 0.015), and a multivariate analysis showed a trend toward worse OS (P = 0.041). Male patients with advanced HCC exhibited an approximately 20-fold higher PD-L1 combined positive score (CPS) compared with those with HCC at an early stage. We successfully generated CD133 CAR-T and PD-1 s cells that could secrete PD-1 blocking scFv based on a sleeping beauty system involving minicircle vectors. CD133 CAR-T and PD-1 s cells exhibited significant antitumour activity against HCC in vitro and in xenograft mouse models. Thus, CD133 CAR-T and PD-1 s cells may be a therapeutically tractable strategy for targeting CD133-positive CSCs in male patients with advanced HCC.

Conclusions
Our study provides a nonviral strategy for constructing CAR-T cells that could also secrete checkpoint blockade inhibitors based on a Sleeping Beauty system from minicircle vectors and revealed a potential benefit of this strategy for male patients with advanced HCC and high CD133 expression (median immunohistochemistry score > 2.284).
Molecular characterization of Glaesserella parasuis strains circulating in North American swine production systems
Authors: Mugabi Robert , Silva Ana Paula S. Poeta , Hu Xiao , Gottschalk Marcelo , Aragon Virginia , Macedo Nubia R. , Sahin Orhan , Harms Perry , Main Rodger , Tucker Alexander W. , Li Ganwu , Clavijo Maria J. 
Published: August 2023

Abstract
Background
Glaesserella parasuis is the causative agent of Glässer’s disease in pigs. Serotyping is the most common method used to type G. parasuis isolates. However, the high number of non-typables (NT) and low discriminatory power make serotyping problematic. In this study, 218 field clinical isolates and 15 G. parasuis reference strains were whole-genome sequenced (WGS). Multilocus sequence types (MLST), serotypes, core-genome phylogeny, antimicrobial resistance (AMR) genes, and putative virulence gene information was extracted.

Results
In silico WGS serotyping identified 11 of 15 serotypes. The most frequently detected serotypes were 7, 13, 4, and 2. MLST identified 72 sequence types (STs), of which 66 were novel. The most predominant ST was ST454. Core-genome phylogeny depicted 3 primary lineages (LI, LII, and LIII), with LIIIA sublineage isolates lacking all vtaA genes, based on the structure of the phylogenetic tree and the number of virulence genes. At least one group 1 vtaA virulence genes were observed in most isolates (97.2%), except for serotype 8 (ST299 and ST406), 15 (ST408 and ST552) and NT (ST448). A few group 1 vtaA genes were significantly associated with certain serotypes or STs. The putative virulence gene lsgB, was detected in 8.3% of the isolates which were predominantly of serotype 5/12. While most isolates carried the bcr, ksgA, and bacA genes, the following antimicrobial resistant genes were detected in lower frequency; blaZ (6.9%), tetM (3.7%), spc (3.7%), tetB (2.8%), bla-ROB-1 (1.8%), ermA (1.8%), strA (1.4%), qnrB (0.5%), and aph3''Ia (0.5%).

Conclusion
This study showed the use of WGS to type G. parasuis isolates and can be considered an alternative to the more labor-intensive and traditional serotyping and standard MLST. Core-genome phylogeny provided the best strain discrimination. These findings will lead to a better understanding of the molecular epidemiology and virulence in G. parasuis that can be applied to the future development of diagnostic tools, autogenous vaccines, evaluation of antibiotic use, prevention, and disease control.
Unravelling factors associated with malaria parasitaemia among children 6–24 months to inform malaria interventions in Nigeria: evidence from 2021 Malaria Indicator Survey
Authors: Ujuju Chinazo N. , Mokuolu Olugbenga A. , Nwafor-Okoli Chinyere , Nnamani Kenechi O. 
Published: August 2023

Abstract
Background
As an additional two million malaria cases were reported in 2021 compared to the previous year, concerted efforts toward achieving a steady decline in malaria cases are needed to achieve malaria elimination goals. This work aimed at determining the factors associated with malaria parasitaemia among children 6–24 months for better targeting of malaria interventions.

Methods
A cross-sectional study analysed 2021 Nigeria Malaria Indicator Survey dataset. Data from 3058 children 6–24 months were analyzed. The outcome variable was children 6–24 months whose parasitaemia was determined using a rapid diagnostic test (RDT). Independent variables include child age in months, mothers’ age, mothers’ education, region, place of residence, household ownership and child use of insecticide-treated net (ITN), exposure to malaria messages and knowledge of ways to prevent malaria. Logistic regression analysis was conducted to examine possible factors associated with malaria parasitaemia in children 6–24 months.

Results
Findings revealed that 28.7% of the 3058 children aged 6–24 months tested positive for malaria by RDT. About 63% of children 12–17 months (aOR = 1.63, 95% CI 1.31–2.03) and 91% of children 18 to 24 months (aOR = 1.91, 95% CI 1.51–2.42) were more likely to have a positive malaria test result. Positive malaria test result was also more likely in rural areas (aOR = 1.79, 95% CI 2.02–24.46), northeast (aOR = 1.54, 95% CI 1.02–2.31) and northwest (aOR = 1.63, 95% CI 1.10–2.40) region. In addition, about 39% of children who slept under ITN had a positive malaria test result (aOR = 1.39 95% CI 1.01–1.90). While children of mothers with secondary (aOR = 0.40, 95% CI 0.29–0.56) and higher (aOR = 0.26, 95% CI 0.16–0.43) levels of education and mothers who were aware of ways of avoiding malaria (aOR = 0.69, 95% CI 0.53–0.90) were less likely to have a malaria positive test result.

Conclusion
As older children 12 to 24 months, children residing in the rural, northeast, and northwest region are more likely to have malaria, additional intervention should target them in an effort to end malaria.
Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery
Authors: El Asmar Antoine , Pop Florin , Helou Etienne El , Demetter Pieter , Veys Isabelle , Polastro Laura , Bohlok Ali , Liberale Gabriel 
Published: August 2023

Abstract
Background
Complete cytoreductive surgery (CRS), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any “peritoneal scar-like tissues” (PST) during CRS, hasn’t been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS ± HIPEC.

Methods
This is a retrospective study, conducted at our comprehensive cancer center, including patients with PMOC, presenting for curative-intent CRS. During CRS, benign-looking peritoneal lesions, lacking the typical hard nodular, aggressive, and invasive morphology, were systematically resected or electro fulgurated. PSTs were analyzed for the presence of tumoral cells by our pathologist. Correlations between the presence of PST and their positivity, and the different patients’ variables, were studied.

Results
In 51% of patients, PST harbored malignant cells. Those were associated with poorly differentiated serous tumors, a high PCI (> 8) and a worse DFS: 17 months in the positive PST group versus 29 months in the negative PST group (p = 0.05), on univariate analysis. Multivariate analysis revealed that PCI > 8 and poorly differentiated primary tumor histology were correlated with a worse DFS, and that higher PCI and advanced FIGO were correlated with a worse OS.

Conclusion
Benign-looking PST harbors malignancy in 51% of cases. The benefit of their systematic resection and their prognostic value should be further investigated in larger cohorts.
Elective nodal irradiation versus involved-field irradiation for stage II–IV cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy: a retrospective propensity study with 8-year survival outcomes
Authors: Wang Jianing , Wu Yajing , Zhang Wei , Chen Yujia , Liu Qing , Jing Shaowu , Zhang Jiandong , Wu Fengpeng , Wang Jun , Qiao Xueying 
Published: August 2023

Abstract
Background
Definitive concurrent chemoradiotherapy (dCCRT) is suggested as the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). This retrospective propensity study compared the 8-year survival outcomes and acute treatment toxicities of these patients treated with elective nodal irradiation (ENI) versus involved-field irradiation (IFI).

Materials and methods
Patients with stage II–IV CESCC treated with dCCRT at the Fourth Hospital of Hebei Medical University between January 1, 2007 and December 31, 2020 were enrolled in the study. All the patients were restaged according to the American Joint Commission 8th edition criteria. The propensity score matching (PSM) was used to minimize the effects of treatment selection bias and potential confounding factors including sex, age, ECOG score, clinical T stage, clinical N stage, clinical TNM stage and radiation dose between the ENI group and IFI group. Survival and the prognostic factors were evaluated.

Results
The 131 eligible patients underwent ENI (60 patients, 45.8%) or IFI (71 patients, 54.2%). The median follow-up time was 91.1 months (range, 23.8–182.0 months) for all the patients. The median OS, 1-, 3-, 5-, and 8-year OS rates were 44.4 months, 87.8%, 55.1%, 38.3%, and 27.2%, respectively. After PSM, there were 49 patients in each group. The median OS, 1-, 3-, 5-, and 8-year OS rates for ENI and IFI group were 32.0 months, 83.7%, 48.5%, 38.5% and 31.1% versus 45.2 months, 89.8%, 52.5%, 37.5%, 26.1%, respectively (P = 0.966; HR 0.99, 95% CI 0.61–1.61). Similar locoregional control was obtained in both groups. The tendency of leukocytopenia and neutropenia was higher in ENI than in IFI (59.2% vs. 38.8%; P = 0.068 and 30.6% vs. 14.3%; P = 0.089) at the end of dCCRT.

Conclusion
Cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy has a satisfactory prognosis with organ conservation. The involved-field irradiation might be a better alternative owing to similar overall survival outcomes and local control with less toxicity of myelosuppression.
A clinical model to predict the progression of knee osteoarthritis: data from Dryad
Authors: Shen Lianwei , Yue Shouwei 
Published: August 2023

Abstract
Background
Knee osteoarthritis (KOA) is a multifactorial, slow-progressing, non-inflammatory degenerative disease primarily affecting synovial joints. It is usually induced by advanced age and/or trauma and eventually leads to irreversible destruction of articular cartilage and other tissues of the joint. Current research on KOA progression has limited clinical application significance. In this study, we constructed a prediction model for KOA progression based on multiple clinically relevant factors to provide clinicians with an effective tool to intervene in KOA progression.

Method
This study utilized the data set from the Dryad database which included patients with Kellgren–Lawrence (KL) grades 2 and 3. The KL grades was determined as the dependent variable, while 15 potential predictors were identified as independent variables. Patients were randomized into training set and validation set. The training set underwent LASSO analysis, model creation, visualization, decision curve analysis and internal validation using R language. The validation set is externally validated and F1-score, precision, and recall are computed.

Result
A total of 101 patients with KL2 and 94 patients with KL3 were selected. We randomly split the data set into a training set and a validation set by 8:2. We filtered “BMI”, “TC”, “Hypertension treatment”, and “JBS3 (%)” to build the prediction model for progression of KOA. Nomogram used to visualize the model in R language. Area under ROC curve was 0.896 (95% CI 0.847–0.945), indicating high discrimination. Mean absolute error (MAE) of calibration curve = 0.041, showing high calibration. MAE of internal validation error was 0.043, indicating high model calibration. Decision curve analysis showed high net benefit. External validation of the metabolic syndrome column-line graph prediction model was performed by the validation set. The area under the ROC curve was 0.876 (95% CI 0.767–0.984), indicating that the model had a high degree of discrimination. Meanwhile, the calibration curve Mean absolute error was 0.113, indicating that the model had a high degree of calibration. The F1 score is 0.690, the precision is 0.667, and the recall is 0.714. The above metrics represent a good performance of the model.

Conclusion
We found that KOA progression was associated with four variable predictors and constructed a predictive model for KOA progression based on the predictors. The clinician can intervene based on the nomogram of our prediction model.

Key information
This study is a clinical predictive model of KOA progression. KOA progression prediction model has good credibility and clinical value in the prevention of KOA progression.
Ultrasound characteristics of follicular and parafollicular thyroid neoplasms: diagnostic performance of artificial neural network
Authors: Cordes Michael , Götz Theresa Ida , Coerper Stephan , Kuwert Torsten , Schmidkonz Christian 
Published: August 2023

Abstract
Background
Ultrasound is the first-line imaging modality for detection and classification of thyroid nodules. Certain features observable by ultrasound have recently been equated with potential malignancy. This retrospective cohort study was conducted to test the hypothesis that radiomics of the four categorical divisions (medullary [MTC], papillary [PTC], or follicular [FTC] carcinoma and follicular thyroid adenoma [FTA]) demonstrate distinctive sonographic characteristics. Using an artificial neural network model for proof of concept, these sonographic features served as input.

Methods
A total of 148 patients were enrolled for study, all with confirmed thyroid pathology in one of the four named categories. Preoperative ultrasound profiles were obtained via standardized protocols. The neural network consisted of seven input neurons; three hidden layers with 50, 250, and 100 neurons, respectively; and one output layer.

Results
Radiomics of contour, structure, and calcifications differed significantly according to nodule type (p = 0.025, p = 0.032, and p = 0.0002, respectively). Levels of accuracy shown by artificial neural network analysis in discriminating among categories ranged from 0.59 to 0.98 (95% confidence interval [CI]: 0.57–0.99), with positive and negative predictive ranges of 0.41–0.99 and 0.78–0.97, respectively.

Conclusions
Our data indicate that some MTCs, PTCs, FTCs, and FTAs have distinctive sonographic characteristics. However, a significant overlap of these characteristics may impede an explicit classification. Further prospective investigations involving larger patient and nodule numbers and multicenter access should be pursued to determine if neural networks of this sort are beneficial, helping to classify neoplasms of the thyroid gland.
Opening of Cx43-formed hemichannels mediates the Ca2+ signaling associated with endothelial cell migration
Authors: Espinoza Hilda , Figueroa Xavier F. 
Published: August 2023

AbstractEndothelial cell migration is a key process in angiogenesis. Progress of endothelial cell migration is orchestrated by coordinated generation of Ca2+ signals through a mechanism organized in caveolar microdomains. Connexins (Cx) play a central role in coordination of endothelial cell function, directly by cell-to-cell communication via gap junction and, indirectly, by the release of autocrine/paracrine signals through Cx-formed hemichannels. However, Cx hemichannels are also permeable to Ca2+ and Cx43 can be associated with caveolin-1, a structural protein of caveolae. We proposed that endothelial cell migration relies on Cx43 hemichannel opening. Here we show a novel mechanism of Ca2+ signaling in endothelial cell migration. The Ca2+ signaling that mediates endothelial cell migration and the subsequent tubular structure formation depended on Cx43 hemichannel opening and is associated with the translocation of Cx43 with caveolae to the rear part of the cells. These findings indicate that Cx43 hemichannels play a central role in endothelial cell migration and provide new therapeutic targets for the control of deregulated angiogenesis in pathological conditions such as cancer.
3DDPDs: describing protein dynamics for proteochemometric bioactivity prediction. A case for (mutant) G protein-coupled receptors
Authors: Gorostiola González Marina , van den Broek Remco L. , Braun Thomas G. M. , Chatzopoulou Magdalini , Jespers Willem , IJzerman Adriaan P. , Heitman Laura H. , van Westen Gerard J. P. 
Published: August 2023

AbstractProteochemometric (PCM) modelling is a powerful computational drug discovery tool used in bioactivity prediction of potential drug candidates relying on both chemical and protein information. In PCM features are computed to describe small molecules and proteins, which directly impact the quality of the predictive models. State-of-the-art protein descriptors, however, are calculated from the protein sequence and neglect the dynamic nature of proteins. This dynamic nature can be computationally simulated with molecular dynamics (MD). Here, novel 3D dynamic protein descriptors (3DDPDs) were designed to be applied in bioactivity prediction tasks with PCM models. As a test case, publicly available G protein-coupled receptor (GPCR) MD data from GPCRmd was used. GPCRs are membrane-bound proteins, which are activated by hormones and neurotransmitters, and constitute an important target family for drug discovery. GPCRs exist in different conformational states that allow the transmission of diverse signals and that can be modified by ligand interactions, among other factors. To translate the MD-encoded protein dynamics two types of 3DDPDs were considered: one-hot encoded residue-specific (rs) and embedding-like protein-specific (ps) 3DDPDs. The descriptors were developed by calculating distributions of trajectory coordinates and partial charges, applying dimensionality reduction, and subsequently condensing them into vectors per residue or protein, respectively. 3DDPDs were benchmarked on several PCM tasks against state-of-the-art non-dynamic protein descriptors. Our rs- and ps3DDPDs outperformed non-dynamic descriptors in regression tasks using a temporal split and showed comparable performance with a random split and in all classification tasks. Combinations of non-dynamic descriptors with 3DDPDs did not result in increased performance. Finally, the power of 3DDPDs to capture dynamic fluctuations in mutant GPCRs was explored. The results presented here show the potential of including protein dynamic information on machine learning tasks, specifically bioactivity prediction, and open opportunities for applications in drug discovery, including oncology.