bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical phenotyping of plasma thrombospondin-2 reveals relationship to right ventricular structure and function in pulmonary hypertension
Authors: Dittrich Anna M. , Mienert Julia , Pott Julian , Engels Lena , Sinning Christoph , Hennigs Jan K. , Klose Hans , Harbaum Lars 
Published: January 2023

BackgroundConverging evidence from proteogenomic analyses prioritises thrombospondin-2 (TSP2) as a potential biomarker for idiopathic or heritable pulmonary arterial hypertension (PAH). We aimed to assess TSP2 levels in different forms of pulmonary hypertension (PH) and to define its clinical phenotype.MethodsAbsolute concentrations of TSP2 were quantified in plasma samples from a prospective single-centre cohort study including 196 patients with different forms of PH and 16 disease controls (suspected PH, but normal resting pulmonary haemodynamics). In an unbiased approach, TSP2 levels were related to 152 clinical variables.ResultsConcentrations of TSP2 were increased in patients with PHversusdisease controls (p<0.001 for group comparison). The discriminatory ability of TSP2 levels to distinguish between patients and controls was superior to that of N-terminal pro-brain natriuretic peptide (p=0.0023 for comparison of areas under the curve). Elevation of TSP2 levels was consistently found in subcategories of PAH, in PH due to lung disease and due to left heart disease. Phenotypically, TSP2 levels were robustly related to echocardiographic markers that indicate the right ventricular (RV) response to chronically increased afterload with increased levels in patients with impaired systolic function and ventriculoarterial uncoupling. Focusing on PAH, increased TSP2 levels were able to distinguish between adaptive and maladaptive RV phenotypes (area under the curve 0.87, 95% CI 0.76–0.98).InterpretationThe study indicates that plasma TSP2 levels inform on the presence of PH and associate with clinically relevant RV phenotypes in the setting of increased afterload, which may provide insight into processes of RV adaptability.
Feature importance measures from random forest regressor using near-infrared spectra for predicting carbonization characteristics of kraft lignin-derived hydrochar
Authors: Hwang Sung-Wook , Chung Hyunwoo , Lee Taekyeong , Kim Jungkyu , Kim YunJin , Kim Jong-Chan , Kwak Hyo Won , Choi In-Gyu , Yeo Hwanmyeong 
Published: January 2023

AbstractThis study investigated the feature importance of near-infrared spectra from random forest regression models constructed to predict the carbonization characteristics of hydrochars produced by hydrothermal carbonization of kraft lignin. The model achieved high coefficients of determination of 0.989, 0.988, and 0.985 with root mean square errors of 0.254, 0.003, and 0.008 when predicting the carbon content, atomic O/C ratio, and H/C ratio, respectively. The random forest models outperformed the multilayer perceptron models for all predictions. In the feature importance analysis, the spectral regions at 1600–1800 nm, the first overtone of C–H stretching vibrations, and 2000–2300 nm, the combination bands, were highly important for predicting the carbon content and O/C predictions, whereas the region at 1250–1711 nm contributed to predicting H/C. The random forest models trained with the high-importance regions achieved better prediction performances than those trained with the entire spectral range, demonstrating the usefulness of the feature importance yielded by the random forest and the feasibility of selective application of the spectral data.
Dyskinesia as a unique presentation of subarachnoid hemorrhage: a case report
Authors: Jaffery Aleq , Morchel Herman , Poon Jessica 
Published: January 2023

Abstract
Background
Subarachnoid hemorrhage (SAH) is a diagnosis that emergency physicians must have a high index of suspicion for. Many common chief complaints such as headache, nausea, altered mental status, and even syncope may alert clinicians to the possibility of a SAH.

Case presentation
The authors present an unusual case of SAH in a patient presenting with acute dyskinesia and altered mental status, which has seldom been documented as the presenting feature of SAH, as well as the diagnostic pitfalls encountered in assessing this patient.

Conclusion
Emergency physicians should maintain a high index of suspicion for dangerous pathology in cases without a clear etiology; they should also utilize metacognition to assess their own biases and thought patterns so as to avoid missing critical diagnoses.
Comparative transcriptome analysis of skin color-associated genes in leopard coral grouper (Plectropomus leopardus)
Authors: Wu Hung-Yi , Chen Kao-Sung , Huang You-Syu , Hsieh Hern-Yi , Tsai HsinYuan 
Published: January 2023

Abstract
Background
The leopard coral grouper (Plectropomus leopardus) is an important economic species in East Asia-Pacific countries. To meet the market demand, leopard coral grouper is facing overfishing and their population is rapidly declining. With the improvement of the artificial propagation technique, the leopard coral grouper has been successfully cultured by Fisheries Research Institute in Taiwan. However, the skin color of farmed individuals is often lacking bright redness. As such, the market price of farmed individuals is lower than wild-type.

Results
To understand the genetic mechanisms of skin coloration in leopard coral grouper, we compared leopard coral grouper with different skin colors through transcriptome analysis. Six cDNA libraries generated from wild-caught leopard coral grouper with different skin colors were characterized by using the Illumina platform. Reference-guided de novo transcriptome data of leopard coral grouper obtained 24,700 transcripts, and 1,089 differentially expressed genes (DEGs) were found between red and brown skin color individuals. The results showed that nine candidate DEGs (epha2, sema6d, acsl4, slc7a5, hipk1, nol6, timp2, slc25a42, and kdf1) significantly associated with skin color were detected by using comparative transcriptome analysis and quantitative real-time polymerase chain reaction (qRT-PCR).

Conclusions
The findings may provide genetic information for further skin color research, and to boost the market price of farmed leopard coral grouper by selective breeding.
Oropharyngeal, proximal colonic, and vaginal microbiomes of healthy Korean native black pig gilts
Authors: Bugenyi Andrew Wange , Lee Ma-Ro , Choi Yeon-Jae , Song Ki-Duk , Lee Hak-Kyo , Son Young-Ok , Lee Dong-Sun , Lee Sang-Chul , Son Young-June , Heo Jaeyoung 
Published: January 2023

Abstract
Background
Exploring the microbiome in multiple body sites of a livestock species informs approaches to promote its health and performance through efficient and sustainable modulation of these microbial ecosystems. Here, we employed 16S rRNA gene sequencing to describe the microbiome in the oropharyngeal cavity, proximal colon, and vaginal tract of Jeju Black pigs (JBP), which are native to the Korean peninsula.

Results
We sampled nine 7-month-old JBP gilts raised under controlled conditions. The most abundant phyla that we found within the oropharyngeal microbiota were Proteobacteria, Bacteroidetes, Fusobacteria and Firmicutes, collectively providing core features from twenty-five of their genera. We also found a proximal colonic microbial core composed of features from twenty of the genera of the two predominant phyla, Firmicutes, and Bacteroidetes. Remarkably, within the JBP vaginal microbiota, Bacteroidetes dominated at phylum level, contrary to previous reports regarding other pig breeds. Features of the JBP core vaginal microbiota, came from seventeen genera of the major phyla Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. Although these communities were distinct, we found some commonalities amongst them. Features from the genera Streptococcus, Prevotella, Bacillus and an unclassified genus of the family Ruminococcaceae were ubiquitous across the three body sites. Comparing oropharyngeal and proximal colonic communities, we found additional shared features from the genus Anaerorhabdus. Between oropharyngeal and vaginal ecosystems, we found other shared features from the genus Campylobacter, as well as unclassified genera from the families Fusobacteriaceae and Flavobacteriaceae. Proximal colonic and vaginal microbiota also shared features from the genera Clostridium, Lactobacillus, and an unclassified genus of Clostridiales.

Conclusions
Our results delineate unique and ubiquitous features within and across the oropharyngeal, proximal colonic and vaginal microbial communities in this Korean native breed of pigs. These findings provide a reference for future microbiome-focused studies and suggest a potential for modulating these communities, utilizing ubiquitous features, to enhance health and performance of the JBP.
The plastid genome of twenty-two species from Ferula, Talassia, and Soranthus: comparative analysis, phylogenetic implications, and adaptive evolution
Authors: Qin Huan-Huan , Cai Jing , Liu Chang-Kun , Zhou Ren-Xiu , Price Megan , Zhou Song-Dong , He Xing-Jin 
Published: January 2023

AbstractBackgroundTheFerulagenus encompasses 180–185 species and is one of the largest genera in Apiaceae, with many ofFerulaspecies possessing important medical value. The previous studies provided more information forFerula, but its infrageneric relationships are still confusing. In addition, its genetic basis of its adaptive evolution remains poorly understood. Plastid genomes with more variable sites have the potential to reconstruct robust phylogeny in plants and investigate the adaptive evolution of plants. Although chloroplast genomes have been reported within theFerulagenus, few studies have been conducted using chloroplast genomes, especially for endemic species in China.ResultsComprehensively comparative analyses of 22 newly sequenced and assembled plastomes indicated that these plastomes had highly conserved genome structure, gene number, codon usage, and repeats type and distribution, but varied in plastomes size, GC content, and the SC/IR boundaries. Thirteen mutation hotspot regions were detected and they would serve as the promising DNA barcodes candidates for species identification inFerulaand related genera. Phylogenomic analyses with high supports and resolutions showed thatTalassia transiliensisandSoranthus meyeriwere nested in theFerulagenus, and thus they should be transferred into theFerulagenus. Our phylogenies also indicated the monophyly of subgeneraSinoferulaand subgeneraNarthexinFerulagenus. Twelve genes with significant posterior probabilities for codon sites were identified in the positively selective analysis, and their function may relate to the photosystem II, ATP subunit, and NADH dehydrogenase. Most of them might play an important role to helpFerulaspecies adapt to high-temperatures, strong-light, and drought habitats.ConclusionPlastome data is powerful and efficient to improve the support and resolution of the complicatedFerulaphylogeny. Twelve genes with significant posterior probabilities for codon sites were helpful forFerulato adapt to the harsh environment. Overall, our study supplies a new perspective for comprehending the phylogeny and evolution ofFerula.
Low thyroid function is associated with an increased risk of advanced fibrosis in patients with metabolic dysfunction-associated fatty liver disease
Authors: Fan Hong , Li Lili , Liu Zhenqiu , Zhang Pengyan , Wu Sheng , Han Xinyu , Chen Xingdong , Suo Chen , Cao Liou , Zhang Tiejun 
Published: January 2023

Abstract
Aims
Observational studies showed that low thyroid function may perturb liver function. We aimed to evaluate the association of low thyroid function with both metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced hepatic fibrosis.

Methods
Participants who underwent abdominal ultrasonography and thyroid function test in a Chinese hospital from 2015 to 2021were enrolled. Fibrosis-4 index (FIB-4) > 2.67 and/or non-alcoholic fatty liver disease fibrosis score (NFS) > 0.676 were used to define advanced fibrosis. Descriptive analyses were performed to characterize the epidemiology of MAFLD according to levels of thyroid-stimulating hormone (TSH). The logistic regression model was applied to estimate the association of low thyroid function with MAFLD and advanced fibrosis.

Results
A total of 19,946 participants (52.78% males, mean age: 47.31 years, 27.55% MAFLD) were included, among which 14,789 were strict-normal thyroid function, 4,328 were low-normal thyroid function, 829 were subclinical hypothyroidism. TSH levels were significantly higher in MAFLD patients with a FIB-4 > 2.67 and /or NFS > 0.676 than their counterparts. The logistic regression model adjusted for age and sex showed that low-normal thyroid function increased the risk of MAFLD (odds ratio [OR] = 1.09; 95% confidence interval [CI] 1.01–1.18). Multivariable regression model adjusted for age, sex, body mass index, type 2 diabetes, and hypertension showed low-normal thyroid function increased the risk of advanced fibrosis in patients with MAFLD (FIB-4 > 2.67: OR = 1.41, 95% CI 1.02–1.93; NFS > 0.676: OR = 1.72, 95% CI 1.08–2.72).

Conclusion
Elevated TSH concentrations are associated with advanced hepatic fibrosis, even in the euthyroid state.
Deep medullary veins: a promising neuroimaging marker for mild cognitive impairment in outpatients
Authors: Chen Xiuqi , Luo Yufan , Zhang Shufan , Yang Xiaoli , Dong Zhiyuan , Wang Yilin , Wu Danhong 
Published: January 2023

Abstract
Background and purpose
Mild cognitive impairment is an age-dependent pre-dementia state caused by varied reasons. Early detection of MCI helps handle dementia. Vascular factors are vital for the occurrence of MCI. This study investigates the correlation between deep medullary veins and multi-dimensional cognitive outcomes.

Materials and methods
A total of 73 participants with MCI and 32 controls were enrolled. Minimum Mental State Examination and Montreal Cognitive Assessment were used to examine the global cognitive function, and different cognitive domains were measured by specific neuropsychological tests. MRI was used to assess the visibility of the DMV and other neuroimage markers.

Results
DMV score was statistically significantly higher in the MCI group compared with the control group (P = 0.009) and independently related to MCI (P = 0.007). Linear regression analysis verified that DMV score was linearly related to global cognition, memory, attention, and executive function after adjusting for cerebrovascular risk factors.

Conclusion
DMV score was independently related to the onset of MCI, and correlates with overall cognition, memory, attention, and executive function in outpatients.
PD-L1 is highly expressed in ovarian cancer and associated with cancer stem cells populations expressing CD44 and other stem cell markers
Authors: Alwosaibai Kholoud , Aalmri Salmah , Mashhour Miral , Ghandorah Salim , Alshangiti Abdulraheem , Azam Faisal , Selwi Waleed , Gharaibeh Lubna , Alatawi Yasser , Alruwaii Zainab , Alsaab Hashem O. 
Published: January 2023

Abstract
Background
Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer.

Methods
A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients’ medical record to investigate the association with PD-L1, TILs, and stem cells expressions.

Results
We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5.

Conclusions
PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.
The efficacy of small molecule anti-angiogenic drugs in previously treated Thymic carcinoma
Authors: Guan Yelan , Gu Xiaodong , Si Jinfei , Xiang Jing , Wei Jingwen , Hao Yue , Wang Wenxian , Sun Yan 
Published: January 2023

Abstract
Background
Antiangiogenic drugs have shown initial efficacy in the treatment of advanced thymic carcinomas (TCs); however, data are limited. In this study, we provide real-world data relating to the efficacy of antiangiogenic drugs for the treatment of patients with TCs.

Methods
We retrospectively collected data on clinical progress after first-line chemotherapy in TCs patients who were treated with small molecule antiangiogenic drugs at our institution between January 2010 and December 2021. Tumor response was evaluated according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Progression free survival and overall survival were calculated using the Kaplan-Meier method.

Results
Of the 17 patients enrolled, 13 (76.5%) received apatinib and four (23.5%) anlotinib monotherapy with an objective response rate of 23.5%. Eleven (64.7%) patients had stable disease. The median follow-up period was 46.0 months (95% confidence interval [CI], 33.0–59.0 months). The median progression survival and overall survival were 7.9 months (95% CI, 6.5–9.3) and 47.0 months (95% CI, 35.4–58.6), respectively. In the 13 patients receiving apatinib, the median PFS was 7.0 months (95% CI, 5.0–9.0), compared with 8.0 months (95% CI, 2.7–13.3 months) for patients in the anlotinib group (P = 0.945). The most common grade 3 adverse events (AEs) were hypertension (n = 3, 23.1%), followed by proteinuria and hand-foot syndrome (HFS, n = 2, 15.4%). There were no grade 4 AEs although eight patients (47.1%) required mid-course discontinuation.

Conclusion
For refractory TCs, small molecule antiangiogenic drugs are efficacious as second- or post-line treatments. The toxicity of antiangiogenic therapy is manageable.
Inference of core needle biopsy whole slide images requiring definitive therapy for prostate cancer
Authors: Tsuneki Masayuki , Abe Makoto , Ichihara Shin , Kanavati Fahdi 
Published: January 2023

Abstract
Background
Prostate cancer is often a slowly progressive indolent disease. Unnecessary treatments from overdiagnosis are a significant concern, particularly low-grade disease. Active surveillance has being considered as a risk management strategy to avoid potential side effects by unnecessary radical treatment. In 2016, American Society of Clinical Oncology (ASCO) endorsed the Cancer Care Ontario (CCO) Clinical Practice Guideline on active surveillance for the management of localized prostate cancer.

Methods
Based on this guideline, we developed a deep learning model to classify prostate adenocarcinoma into indolent (applicable for active surveillance) and aggressive (necessary for definitive therapy) on core needle biopsy whole slide images (WSIs). In this study, we trained deep learning models using a combination of transfer, weakly supervised, and fully supervised learning approaches using a dataset of core needle biopsy WSIs (n=1300). In addition, we performed an inter-rater reliability evaluation on the WSI classification.

Results
We evaluated the models on a test set (n=645), achieving ROC-AUCs of 0.846 for indolent and 0.980 for aggressive. The inter-rater reliability evaluation showed s-scores in the range of 0.10 to 0.95, with the lowest being on the WSIs with both indolent and aggressive classification by the model, and the highest on benign WSIs.

Conclusion
The results demonstrate the promising potential of deployment in a practical prostate adenocarcinoma histopathological diagnostic workflow system.
A delta-radiomic lymph node model using dynamic contrast enhanced MRI for the early prediction of axillary response after neoadjuvant chemotherapy in breast cancer patients
Authors: Liu Shasha , Du Siyao , Gao Si , Teng Yuee , Jin Feng , Zhang Lina 
Published: January 2023

Abstract
Background
The objective of this paper is to explore the value of a delta-radiomic model of the axillary lymph node (ALN) using dynamic contrast-enhanced (DCE) MRI for early prediction of the axillary pathological complete response (pCR) of breast cancer patients after neoadjuvant chemotherapy (NAC).

Methods
A total of 120 patients with ALN-positive breast cancer who underwent breast MRI before and after the first cycle of NAC between October 2018 and May 2021 were prospectively included in this study. Patients were divided into a training (n = 84) and validation (n = 36) cohort based on the temporal order of their treatments. Radiomic features were extracted from the largest slice of targeted ALN on DCE-MRI at pretreatment and after one cycle of NAC, and their changes (delta-) were calculated and recorded. Logistic regression was then applied to build radiomic models using the pretreatment (pre-), first-cycle(1st-), and changes (delta-) radiomic features separately. A clinical model was also built and combined with the radiomic models. The models were evaluated by discrimination, calibration, and clinical application and compared using DeLong test.

Results
Among the three radiomic models, the ALN delta-radiomic model performed the best with AUCs of 0.851 (95% CI: 0.770–0.932) and 0.822 (95% CI: 0.685–0.958) in the training and validation cohorts, respectively. The clinical model yielded moderate AUCs of 0.742 (95% CI: 0.637–0.846) and 0.723 (95% CI: 0.550–0.896), respectively. After combining clinical features to the delta-radiomics model, the efficacy of the combined model (AUC = 0.932) in the training cohort was significantly higher than that of both the delta-radiomic model (Delong p = 0.017) and the clinical model (Delong p < 0.001) individually. Additionally, in the validation cohort, the combined model had the highest AUC (0.859) of any of the models we tested although this was not statistically different from any other individual model’s validation AUC. Calibration and decision curves showed a good agreement and a high clinical benefit for the combined model.

Conclusion
This preliminary study indicates that ALN-based delta-radiomic model combined with clinical features is a promising strategy for the early prediction of downstaging ALN status after NAC. Future axillary MRI applications need to be further explored.