bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival trends and prognostic factors for patients with extramedullary plasmacytoma: A population-based study
Authors: Shen Xuxing , Zhang Lina , Wang Jing , Chen Lijuan , Liu Shu , Zhang Run 
Published: December 2022

BackgroundExtramedullary plasmacytoma (EMP) is a localized plasma cell neoplasm that originates from tissues other than bone. The survival trends and prognostic factors of patients with EMP in recent years remain unreported.MethodsWe used the SEER databases to extract the data. Survival curves were calculated using the Kaplan-Meier method and a nomogram was created based on the Cox’s proportional hazards model.ResultsA total of 1676 cases of EMP were identified. Patients in period-2 (2008-2016) show similar survival (p=0.8624) to those in period-1(1975-2007). Age, gender, race, and sites were prognostic of patient outcomes. And the use of surgery was associated with improved survival. The patients were randomly assigned to the training cohort and the validation cohort in a ratio of 2:1. Four factors including age, gender, race, and sites were identified to be independently predictive of the overall survival of patients with EMP. A prognostic model (EMP prognostic index, EMP-PI) comprising these four factors was constructed. Within the training cohort, three risk groups displayed significantly different 10-year survival rates: low-risk (73.0%, [95%CI 66.9-78.2]), intermediate-risk (39.3%, [95%CI 34.3-44.3]), and high-risk (22.6%, [95%CI 15.3-30.9]) (p&lt;0.0001). Three risk groups were confirmed in the internal validation cohort. We also constructed a 5-factor nomogram based on multivariate logistic analyses.ConclusionThe survival of patients with EMP did not improve in recent years. The EMP-PI will facilitate the risk stratification and guide the risk-adapted therapy in patients with EMP.
Prognostic value of KRAS subtype in patients with PDAC undergoing radical resection
Authors: Dai Manxiong , Jahanzaib Raja , Liao Yan , Yao Fengxuan , Li Jia , Teng Xiong , Chen Kang , Cheng Wei 
Published: December 2022

ObjectiveTo explore the frequency distribution of KRAS mutant subtypes in patients with resectable PDAC in China and then evaluate the prognostic value of different KRAS subtypes in patients with PDAC undergoing radical resection.MethodsThe clinicopathological data and gene test reports of 227 patients undergoing PDAC radical surgery at Hunan Provincial People’s Hospital from 1 January 2016 to 1 January 1 2020 were retrospectively evaluated. There were 118 men (52%) and 109 women (48%). The mean age was 58.8 ± 10.3 years. After univariate analysis of the clinicopathological factors (sex, age, presence or absence of underlying disease, location of the primary tumour, tumour TNM stage, T stage, N stage, presence or absence of vascular invasion, presence or absence of nerve invasion, surgical margin, KRAS mutation subtype), variables with P &lt; 0.1 were included in the multivariate Cox regression model analysis, and the log-rank sum test and Kaplan−Meier curves were used to assess the correlation of the KRAS mutation subtype with the overall survival time.ResultsKRAS mutations were detected in 184 of 227 patients (81.1%) (G12D: 66; G12V: 65; G12R: 27; Q61:26) and were not detected in 43 patients (18.9%). KRAS mutations were associated with tumour differentiation (P = 0.001), TNM stage (P = 0.013), and T stage (P &lt; 0.001). Multivariate Cox regression model analysis showed that N stage, surgical margin, tumour differentiation, and KRAS-G12D mutation were independent prognostic factors for DFS and OS. Patients with the KRAS-G12D subtype had shorter OS with a median OS of 12 months (HR: 0.55, CI: 0.39–0.77, P &lt; 0.001), and patients with KRAS wild-type had longer OS with a median OS of 19 months (HR: 0.57, CI: 0.42–0.76, P &lt; 0.001).ConclusionKRAS wild-type individuals are more prevalent in the Chinese population than in European or American populations. Patients undergoing surgery had a reduced percentage of tumors with KRAS-G12D. When determining the prognosis of individuals with radically resected PDAC, reference markers for KRAS mutation subtypes can be employed.
Diagnosis of architectural distortion on digital breast tomosynthesis using radiomics and deep learning
Authors: Chen Xiao , Zhang Yang , Zhou Jiahuan , Wang Xiao , Liu Xinmiao , Nie Ke , Lin Xiaomin , He Wenwen , Su Min-Ying , Cao Guoquan , Wang Meihao 
Published: December 2022

PurposeTo implement two Artificial Intelligence (AI) methods, radiomics and deep learning, to build diagnostic models for patients presenting with architectural distortion on Digital Breast Tomosynthesis (DBT) images.Materials and MethodsA total of 298 patients were identified from a retrospective review, and all of them had confirmed pathological diagnoses, 175 malignant and 123 benign. The BI-RADS scores of DBT were obtained from the radiology reports, classified into 2, 3, 4A, 4B, 4C, and 5. The architectural distortion areas on craniocaudal (CC) and mediolateral oblique (MLO) views were manually outlined as the region of interest (ROI) for the radiomics analysis. Features were extracted using PyRadiomics, and then the support vector machine (SVM) was applied to select important features and build the classification model. Deep learning was performed using the ResNet50 algorithm, with the binary output of malignancy and benignity. The Gradient-weighted Class Activation Mapping (Grad-CAM) method was utilized to localize the suspicious areas. The predicted malignancy probability was used to construct the ROC curves, compared by the DeLong test. The binary diagnosis was made using the threshold of ≥ 0.5 as malignant.ResultsThe majority of malignant lesions had BI-RADS scores of 4B, 4C, and 5 (148/175 = 84.6%). In the benign group, a substantial number of patients also had high BI-RADS ≥ 4B (56/123 = 45.5%), and the majority had BI-RADS ≥ 4A (102/123 = 82.9%). The radiomics model built using the combined CC+MLO features yielded an area under curve (AUC) of 0.82, the sensitivity of 0.78, specificity of 0.68, and accuracy of 0.74. If only features from CC were used, the AUC was 0.77, and if only features from MLO were used, the AUC was 0.72. The deep-learning model yielded an AUC of 0.61, significantly lower than all radiomics models (p&lt;0.01), which was presumably due to the use of the entire image as input. The Grad-CAM could localize the architectural distortion areas.ConclusionThe radiomics model can achieve a satisfactory diagnostic accuracy, and the high specificity in the benign group can be used to avoid unnecessary biopsies. Deep learning can be used to localize the architectural distortion areas, which may provide an automatic method for ROI delineation to facilitate the development of a fully-automatic computer-aided diagnosis system using combined AI strategies.
Pharmacist-led olaparib follow-up service for ambulatory ovarian cancer patients: A prospective study in a tertiary specialized cancer hospital in China
Authors: Wang Yanting , Du Di , Yang Jun , Lau Alan H. , Dai Yuanyuan , Qin Wangjun , Li Ning , Li Guohui 
Published: December 2022

Purpose: To establish a pharmacist-led olaparib follow-up program for ovarian cancer patients, provide patient education, get information on adverse drug reactions (ADRs), and identify and manage drug-related problems.Methods: Ambulatory adult patients with ovarian cancer receiving olaparib were enrolled. At least one follow-up session was conducted by clinical pharmacists. Pharmacists collected data on the type and grade of ADRs, drug adherence, olaparib dosing, concomitant medications, and pharmacists’ suggestions.Results: 83 patients were enrolled with the median age of 58. The average number of the follow-up sessions provided to each patient was 1.31, and the average duration of each follow-up was 17.78 min. The olaparib starting dose for most patients (97.59%) was 600 mg/d. 36.14% of the patients had missed olaparib doses and 27.71% of the patients had dose adjustments due to ADRs. The most common ADRs (incidence≥10%) were: fatigue (40.96%), anemia (36.14%), leukopenia (36.14%), nausea (28.92%), thrombocytopenia (16.87%), anorexia (16.87%), dyspepsia (15.66%). The tolerability profiles were generally similar between patients treated for “first-line maintenance” and those treated for “recurrence maintenance” (p &gt; .05). There were 42% of the patients who were concomitantly taking medications without exact chemical contents (such as formulated Chinese medicines and Chinese decoctions), and common types of concomitant medications with exact drug names were antihypertensive, anti-hyperglycemic, and anti-hyperlipidemic medications. The pharmacists identified 4 clinically significant drug-drug interactions (DDIs) in two patients. Pharmacists made 196 suggestions mainly related to rational use of the medications and management of ADRs.Conclusion: The study provides the first report about pharmacist-led follow-up service for olaparib. The types of ADRs were similar to those previously observed in clinical trials, and the profiles of ADRs in different types of patients (first-line maintenance vs. recurrence maintenance) were also similar. Pharmacists identified drug-related problems (such as adherence, DDIs and management of ADRs) and offer suggestions for the patients.
Cost-effectiveness of janus kinase inhibitors for rheumatoid arthritis: A systematic review and meta-analysis of cost-utility studies
Authors: Kumar S. Sajith , Haridoss Madhumitha , Venkataraman Krishnamurthy , Bagepally Bhavani Shankara 
Published: December 2022

Introduction: Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in rheumatoid arthritis (RA). Synthesized cost-effective evidence would aid in informed decision-making given the similar clinical effectiveness of JAKi, but incongruent cost-effectiveness reports.Methods: Literature search was conducted in PubMed, Embase, Scopus, and Tufts Medical Centers’ cost-effective analysis registry. We pooled the incremental net benefit (INB) with 95% confidence interval (CI) using random-effects model and the heterogeneity was assessed using Cochrane-Q test and I2 statistic. Modified economic evaluation bias checklist was used to assess the quality of selected studies. Publication bias was assessed using a funnel plot and Egger’s test. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment was performed to assess the certainty of outcomes presented.Results: We included seventeen relevant studies for systematic review, of which fifteen were eligible for meta-analysis. The meta-analysis results showed that JAK-i is cost-effective compared to csDMARDS/bDMARDs with a pooled INB (INBp) of $19,886 (95% CI, 1,635 to 38,137) but with considerable heterogeneity (I2 = 99.14). As a second-line treatment for csDMARD failed RA, JAK-i is cost-effective than csDMARD/bDMARD with a pooled INB of $23,144 (74.1–46,214) and high heterogeneity (I2 = 99.67). But on a separate analysis JAK-i as second-line treatment is not cost-effective than TNF-a-i (INBp = $25,813, -5,714 to 57,340). However, leave-one-out analysis found that omitting a single outlier makes JAK-i cost-effective. Further, JAK-i is not cost-effective as a third-line treatment for csDMARD-TNF-a-I failed RA, compared to csDMARDs/bDMARDs with INBp $26,157 (-7,284 to 59,598).Conclusion: Meta-analysis suggests that JAK-i is cost-effective when used after csDMARD failure but not cost-effective when used after csDMARD-TNF-a-i failure with low certainty of evidence.Clinical Trial Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021222541, identifier CRD42021222541
Toward a high-precision mass–energy test of the equivalence principle with atom interferometers
Authors: Zhou Lin , Yan Si-Tong , Ji Yu-Hang , He Chuan , Jiang Jun-Jie , Hou Zhuo , Xu Run-Dong , Wang Qi , Li Zhi-Xin , Gao Dong-Feng , Liu Min , Ni Wei-Tou , Wang Jin , Zhan Ming-Sheng 
Published: December 2022

The equivalence principle (EP) is a basic assumption of the general relativity. The quantum test of the equivalence principle with atoms is an important way to examine the applicable scope of the current physical framework so as to discover new physics. Recently, we extended the traditional pure mass or energy tests of the equivalence principle to the joint test of mass–energy by atom interferometry (Zhou et al.,Phys.Rev.A 104,022822). The violation parameter of mass is constrained to η0 = (−0.8 ± 1.4) × 10–10 and that of internal energy to ηE = (0.0 ± 0.4) × 10–10 per reduced energy ratio. Here, we first briefly outline the joint test idea and experimental results, and then, we analyze and discuss how to improve the test accuracy. Finally, we report the latest experimental progress toward a high-precision mass–energy test of the equivalence principle. We realize atom interference fringes of 2T = 2.6 s in the 10-m long-baseline atom interferometer. This free evolution time T, to the best of our knowledge, is the longest duration realized in the laboratory, and the corresponding resolution of gravity measurement is 4.5 × 10−11 g per shot.
An evaluation of the rat intestinal monoamine biogeography days following exposure to acute stress
Authors: Bauer Ella E. , Reed Carter H. , Lyte Mark , Clark Peter J. 
Published: December 2022

Stress-induced abnormalities in gut monoamine levels (e.g., serotonin, dopamine, norepinephrine) have been linked to gastrointestinal (GI) dysfunction, as well as the worsening of symptoms in GI disorders. However, the influence of stress on changes across the entire intestinal monoamine biogeography has not been well-characterized, especially in the days following stress exposure. Therefore, the aim of this study was to comprehensively assess changes to monoamine neurochemical signatures across the entire rat intestinal tract days after exposure to an acute stressor. To the end, adult male F344 rats were subjected to an episode of unpredictable tail shocks (acute stress) or left undisturbed. Forty-eight hours later rats were euthanized either following a 12 h period of fasting or 30 min of food access to evaluate neurochemical profiles during the peri- and early postprandial periods. Monoamine-related neurochemicals were measured via UHPLC in regions of the small intestine (duodenum, jejunum, ileum), large intestine (cecum, proximal colon, distal colon), cecal contents, fecal contents, and liver. The results suggest a relatively wide-spread increase in measures of serotonin activity across intestinal regions can be observed 48 h after exposure to acute stress, however some evidence was found supporting localized differences in serotonin metabolization. Moreover, acute stress exposure reduced catecholamine-related neurochemical concentrations most notably in the ileum, and to a lesser extent in the cecal contents. Next, stress-related fecal serotonin concentrations were consistent with intestinal profiles. However, fecal dopamine was elevated in association with stress, which did not parallel findings in any other intestinal area. Finally, stress exposure and the food access period together only had minor effects on intestinal monoamine profiles. Taken together, these data suggest nuanced differences in monoaminergic profiles exist across intestinal regions the days following exposure to an acute stressor, highlighting the importance of assessments that consider the entire intestinal tract biogeography when investigating stress-related biological outcomes that may be relevant to GI pathophysiology.
Combinatorial transient gene expression strategies to enhance terpenoid production in plants
Authors: Park Soyoung , Mani Vimalraj , Kim Jin A. , Lee Soo In , Lee Kijong 
Published: December 2022

IntroductionThe monoterpenoid linalool and sesquiterpenoid costunolide are ubiquitous plant components that have been economically exploited for their respective essential oils and pharmaceutical benefits. In general, monoterpenes and sesquiterpenes are produced by the plastid 2-C-methyl-D-erythritol 4-phosphate (MEP) and cytosolic mevalonate (MVA) pathways, respectively. Herein, we investigated the individual and combinatorial potential of MEP and MVA pathway genes in increasing linalool and costunolide production in Nicotiana benthamiana.MethodsFirst, six genes from the MEP (1-deoxy-D-xylulose-5-phosphate synthase, 1-deoxy-D-xylulose 5-phosphate reductoisomerase, 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase, geranyl pyrophosphate synthase, and linalool synthase) and MVA (acetoacetyl-CoA-thiolase, hydroxy-3-methylglutaryl-CoA reductase, farnesyl pyrophosphate synthase, germacrene A synthase, germacrene A oxidase, and costunolide synthase) pathways were separately cloned into the modular cloning (MoClo) golden gateway cassette. Second, the cassettes were transformed individually or in combination into the leaves of N. benthamiana by agroinfiltration.Results and discussionFive days post infiltration (DPI), all selected genes were transiently 5- to 94-fold overexpressed. Quantification using gas chromatography-Q-orbitrap-mass spectrometry (GC-Q-Orbitrap-MS) determined that the individual and combinatorial expression of MEP genes increased linalool production up to 50–90ng.mg-1 fresh leaf weight. Likewise, MVA genes increased costunolide production up to 70–90ng.mg-1 fresh leaf weight. Our findings highlight that the transient expression of MEP and MVA pathway genes (individually or in combination) enhances linalool and costunolide production in plants.
Genetic variation and marker−trait association affect the genomic selection prediction accuracy of soybean protein and oil content
Authors: Sun Bo , Guo Rui , Liu Zhi , Shi Xiaolei , Yang Qing , Shi Jiayao , Zhang Mengchen , Yang Chunyan , Zhao Shugang , Zhang Jie , He Jianhan , Zhang Jiaoping , Su Jianhui , Song Qijian , Yan Long 
Published: December 2022

IntroductionGenomic selection (GS) is a potential breeding approach for soybean improvement.MethodsIn this study, GS was performed on soybean protein and oil content using the Ridge Regression Best Linear Unbiased Predictor (RR-BLUP) based on 1,007 soybean accessions. The SoySNP50K SNP dataset of the accessions was obtained from the USDA-ARS, Beltsville, MD lab, and the protein and oil content of the accessions were obtained from GRIN.ResultsOur results showed that the prediction accuracy of oil content was higher than that of protein content. When the training population size was 100, the prediction accuracies for protein content and oil content were 0.60 and 0.79, respectively. The prediction accuracy increased with the size of the training population. Training populations with similar phenotype or with close genetic relationships to the prediction population exhibited better prediction accuracy. A greatest prediction accuracy for both protein and oil content was observed when approximately 3,000 markers with -log10(P) greater than 1 were included.DiscussionThis information will help improve GS efficiency and facilitate the application of GS.
Genome-wide identification and comprehensive analysis reveal potential roles of long non-coding RNAs in fruit development of southern highbush blueberry (Vaccinium corymbosum L.)
Authors: Li Shuigen , Zhang Jiaying , Zhang Liqing , Fang Xianping , Luo Jun , An Haishan , Zhang Xueying 
Published: December 2022

IntroductionBlueberries have a high antioxidant content and are produced as healthy food worldwide. Long non-coding RNAs (lncRNAs) are a type of regulatory RNAs that play a variety of roles in plants. Nonetheless, information on lncRNAs and their functions during blueberry fruit development is scarce in public databases.MethodsIn the present study, we performed genome-wide identification of lncRNAs in a southern highbush blueberry using strand-specific RNA sequencing (ssRNA-Seq). Differentially expressed lncRNAs (DE-lncRNAs) and their potential target genes were analyzed at four stages of fruit development. Cis-regulatory DE-lncRNAs were predicted using co-localization analysis.ResultsThese findings included a total of 25,036 lncRNAs from 17,801 loci. Blueberry lncRNAs had shorter transcript lengths, smaller open reading frame (ORF) sizes, fewer exons, and fewer isoforms than protein-coding RNAs, as well as lower expression levels and higher stage-specificity during fruit development. A total of 105 DE-lncRNAs were identified among the comparison group of PAD vs. CUP, 443 DE-lncRNAs were detected when comparing CUP with PINK fruits, and 285 DE-lncRNAs were revealed when comparing PINK and BLUE fruits. According to Kyoto Encyclopedia of Genes and Genomes annotation, target genes of DE-lncRNAs were primarily enriched in the “Autophagy-other”, “DNA replication”, “Endocytosis”, ‘photosynthesis’ and ‘chlorophyll metabolism’ pathways, suggesting that lncRNAs may pay potential roles in fruit expansion and ripening. Moreover, several lncRNAs have been proposed as cis-regulators of the key genes involved in flavonoid biosynthesis. MSTRG.107242.6, and its putative target gene, BTB/POZ and TAZ domain-containing protein, might play critical roles in anthocyanin accumulation in blueberries.DiscussionThese findings highlight the regulatory function of lncRNAs and aid in elucidating the molecular mechanism underlying blueberry fruit growth.
The effect of color coding and layout coding on users’ visual search on mobile map navigation icons
Authors: Zhang Mengzhe , Gong Yong , Deng Rong , Zhang Sanyuan 
Published: December 2022

Color and spatial layout are important factors that affect users’ icon cognition and play a huge role in the visual search process of icons. Guided by the user’s interactive needs, this paper aims to improve the visual search efficiency of mobile map navigation icons. The mixed design within and between subjects is adopted through the combination of theoretical and experimental research, and the subjective questionnaire method is used to explore the research. This paper explores the visual search problem of mobile map navigation icons based on color coding and layout coding. The experimental results mainly include reaction time, accuracy rate, user experience, and statistical and variance analysis. The results show that the layout of the mobile map navigation icons significantly impacts the user’s visual search. The navigation icons that use color for layout coding have the highest visual search efficiency and better user experience. Among the icons, the layout with regular color distribution and a larger area of the same color has the highest visual search efficiency for users and the best user experience; the visual search efficiency of navigation icons using color for layout coding is significantly higher than that of mobile map navigation icons.Relevance to industry: The user scale of mobile information maps is huge and the usage rate is high, but the large number of navigation icons increases the burden of user information identification and acquisition. As a result, the efficiency of user information acquisition is low, and the user experience is reduced. A clear, easy-to-search navigation icon design can enhance the user experience of the entire product. The results of this research provide theoretical support and practical guidance for the design optimization and improvement of mobile map navigation icons.