bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origin and implication of two newly identified peraluminous A-type granites in the early Paleozoic orogeny, Southeast Asia
Authors: Shu Xu-Jie , Jiang Wei , Wang Dan , Cheng Cheng , Wang Hong-Zuo 
Published: February 2023

Abstract: The amalgamation of the Yangtze and the Cathaysia Block in Neoproterozoic time led to the formation of the South China Block (SCB) and generated the Jiangnan Orogen with the occurrences of juvenile magmatic rocks. After this orogeny, a typical collisional orogen formed during the early Paleozoic period in Southeast Asia which is mainly distributed in the Wuyi-Nanling-Yunkai area in the SCB. However, the transitional time from syn-collisional compression to post-collisional extension is debatable. Here, we present new data on zircon U-Pb zircon ages, Lu-Hf isotopes, and geochemistry for the Guzhang and Shadi granites from the Nanling area, South China. Both plutons have similar zircon 238U/206Pb ages of ca. 430 Ma. Petrographic and geochemical characteristics (e.g., FeOt/(FeOt+MgO) = 0.82–0.95) indicate that both granites are peraluminous A-type, with high Ga/Al ratios (2.43–2.91) as well as high concentrations of Zr, Nb, Ce, Y (sum values from 327 to 527 ppm), and formation temperature (820°C–845°C). Shadi granite exhibit high positive εHf(t) values (clustering within 0 to +6) while Guzhang granite show relatively lower εHf(t) values (−8.7 to −2.9). Their mildly negative to positive zircon εHf(t) values are higher than that of many coeval granites and can be derived from anhydrous melting of tonalitic genesis in the middle crustal depth, with the Shadi pluton having more orthometamorphite in the source. The ages and Hf isotopic compositions of inherited zircons (εHf(t = 960 Ma) = 9.2, εHf(t = 950 Ma) = 7.3) suggest that the Neoproterozoic juvenile magmatic rocks in the Jiangnan Orogen were a significant source for these granites. We interpret these A-type granites derived at the post-collisional stage. Their occurrence indicates that the geological setting of this Paleozoic orogen shifted from compression to extension no later than 430 Ma.
Different sleep pattern in over-weight/obese women with polycystic ovary syndrome
Authors: Oberg Emma , Blomberg Liselotte , Åkerstedt Torbjörn , Hirschberg Angelica Lindén 
Published: February 2023

ContextSleep duration and sleep quality have important health implications although our knowledge of objectively measured sleep variables in women with Polycystic Ovary Syndrome (PCOS) is limited.ObjectiveTo compare sleep variables assessed by actigraphy in over-weight/obese women with PCOS and controls, and to assess sleep variables after behavioral modification intervention in comparison with minimal intervention in a randomized trial.DesignRandomized controlled trial, and a control group.SettingOutpatient gynecological clinic at a university hospital in Sweden.Participants39 women fulfilling all Rotterdam PCOS criteria, randomized to behavioral modification intervention or minimal intervention and 21 controls with no other metabolic disease, all aged 18‐40 years with a BMI ≥ 27 kg/m2.InterventionA four-month behavioral modification intervention including weekly group meetings focusing on behavioral and healthy lifestyle aspects. Minimal intervention reflecting standard care.Main outcome measureSleep durations and sleep efficiency assessed by actigraphy.ResultsCompared to the control group, women with PCOS had significantly shorter time in bed (501 vs 548 min, p= 0.049), sleep time over 24 hours (448 vs 567 min, p=0.005) and sleep time at night (434 vs 511 min, p=0.002), poorer sleep efficiency (87 vs 93%, p&lt;0.001), and longer wakefulness after sleep onset (64 vs 38 min, p&lt;0.001). However, total sleep time at night for women with PCOS (7.2hrs) was within the normal range. Following behavioral modification intervention, the reduction from baseline in sleep over 24 hours and in the daytime sleep were significant compared to the minimal intervention group (78 min, p=0.009 and 43 min, p=0.003 respectively).ConclusionsWe found over-weight/obese women with PCOS to have normal sleep duration, but worse sleep efficiency than controls. Behavioral modification intervention seems to reduce the amount of daytime sleep, suggesting improved sleep behavior.Clinical trials registrationhttps://doi.org/10.1186/ISRCTN48947168, identifier ISRCTN48947168.
A user-friendly nomogram for predicting radioiodine refractory differentiated thyroid cancer
Authors: Meng Chao , Song Juanjuan , Long Wen , Mu Zhuanzhuan , Sun Yuqing , Liang Jun , Lin Yansong 
Published: February 2023

BackgroundThe diagnosis of radioiodine refractory differentiated thyroid cancer (RAIR-DTC) is primarily based on clinical evolution and iodine uptake over the lesions, which is still time-consuming, thus urging a predictive model for timely RAIR-DTC informing. The aim of this study was to develop a nomogram model for RAIR prediction among DTC patients with distant metastases (DM).MethodsData were extracted from the treatment and follow-up databases of Peking Union Medical College Hospital between 2010 and 2021. A total of 124 patients were included and divided into RAIR (n=71) and non-RAIR (n=53) according to 2015 ATA guidelines. All patients underwent total thyroidectomy followed by at least two courses of RAI treatment. Serological markers and various clinical, pathological, genetic status, and imaging factors were integrated into this study. The pre-treatment stimulated Tg and pre- and post-treatment suppressed Tg at the first and second course RAI treatment were defined as s-Tg1, s-Tg2, sup-Tg1, and sup-Tg2, respectively. Δs-Tg denoted s-Tg1/s-Tg2, and Δs-TSH denoted s-TSH1/s-TSH2. Multivariate logistic regression and correlation analysis were utilized to determine the independent predictors of RAIR. The performance of the nomogram was assessed by internal validation and receiver operating characteristic (ROC) curve, and benefit in clinical decision-making was assessed using decision curve.ResultsIn univariate logistic regression, nine possible risk factors were related to RAIR. Correlation analysis showed four of the above factors associated with RAIR. Through multivariate logistic regression, Δs-Tg/Δs-TSH&lt;1.50 and age upon diagnosis were obtained to develop a convenient nomogram model for predicting RAIR. The model was internally validated and had good predictive efficacy with an AUC of 0.830, specificity of 0.830, and sensitivity of 0.755. The decision curve also showed that if the model is used for clinical decision-making when the probability threshold is between 0.23 and 0.97, the net benefit of patients is markedly higher than that of the TreatAll and TreatNone control groups.By using 1.50 as a cut-off ofΔs-Tg/Δs-TSH, differing biochemical progression among the generally so-called RAIR can be further stratified as meaningfully rapidly or slowly progressive patients (P=0.012).ConclusionsA convenient user-friendly nomogram model was developed with good predictive efficacy for RAIR. The progression of RAIR can be further stratified as rapidly or slowly progressive by using 1.50 as a cut-off value of Δs-Tg/Δs-TSH.
A deep learning-based framework for the operation prediction of primary heat transfer loop in nuclear power plants
Authors: Shi Tianzi , She Jingke , Li Pingfan , Jiang Jianjian , Chen Wei 
Published: February 2023

A deep learning-based multi-node framework is constructed in this work to provide a data-driven platform that provides predictions for the operation condition of the primary heat transfer (PHT) loop in nuclear power plants (NPPs). Several deep learning models that have been verified and demonstrated in previous researches, such as Long-Short Term Memory (LSTM), Convolutional Neural Network (CNN), and zigmoid-based LSTM (zLSTM), are applied to modeling critical system parameters at three important nodes in the PHT loop. The feature extraction and process memory are enhanced via the collaborative work of CNN and LSTM. zLSTM, on the other hand, is successfully utilized to strengthen the long-term memory, especially for predictions of a node with multivariate inputs such as the steam generator. The node prediction results are also adopted for a polynomial fitting that generates an additional input to the next node, allowing each node to select a more accurate input. According to the verification experiments based on Loss of Coolant Accident (LOCA), the Mean Squared Error (MSE) result (1.29 × 10−3) and the Mean Absolute Error (MAE) result (1.37 × 10−2) of 0.7 cm2 LOCA case demonstrate the functionality and accuracy of the proposed framework. It is found that the fitting error (MSE) in the outlet node at 0.7 cm2 case is 38.5% lower than the prediction, showing the advantage of applying both deep learning and fitting methods. The best performance, in term of MSE, is obtained at SG node in the 0.7 cm2 case, where its processing error (0.001285) is 93.2% lower than that of the baseline models. Both the validation and verification experiments successfully proved the feasibility and advantages of the proposed framework, which offers an alternative option for the operation analysis of PHT performance.
Spatial convergence and influencing factors of green total factor productivity of China’s urban agglomerations
Authors: Mao Jinhuang , Yu Zhi , Wang Yifan , Wang Lintao , Wang Meimei 
Published: February 2023

Introduction: Based on the green economic growth theory and the background of comprehensive promotion of high-quality development, the article evaluates and analyzes the dynamic evolution, convergence mechanism and influencing factors of Green Total Factor Productivity (GTFP) growth in 19 major urban agglomerations.Methods: By using the SBM-GML model method, the paper aims to study the existence of differences in green economic operation in urban agglomerations.Results: (1) The GTFP of Chinese urban agglomerations is in an effective state driven by technological progress, and the core driving role of technical efficiency has not been fully exploited, the constraints and limitations of resources, energy and environment on the space of high-quality development of urban agglomerations still exist. (2) There is no δ convergence in the GTFP growth of urban agglomerations, but there is a trend of β convergence, the pattern of coordinated regional development is gradually forming. (3) The eastern urban agglomerations show the competitiveness of green development and spatial convergence rate of GTFP growth better than other regions, and even present a synergistic development situation. (4) Industrial structure and financial service level have positive effects on GTFP growth of urban agglomerations, while business environment and capital deepening level have negative effects on them.Discussion: The research aims to provide reference for decision making to comprehensively promote regional synergistic development strategy in urban agglomerations of mainland China.
An advanced molecular medicine case report of a rare human tumor using genomics, pathomics, and radiomics
Authors: Ma Li , Peterson Erich A. , Shin Ik Jae , Muesse Jason , Marino Katy , Steliga Mathew A. , Atiq Omar , Arnaoutakis Konstantinos , Wardell Christopher , Wooldridge Jacob , Prior Fred , Johann Donald J. 
Published: February 2023

Background: Pulmonary Sclerosing Pneumocytoma (PSP) is a rare tumor of the lung with a low malignant potential that primarily affects females. Initial studies of PSP focused primarily on analyzing features uncovered using conventional X-ray or CT imaging. In recent years, because of the widespread use of next-generation sequencing (NGS), the study of PSP at the molecular-level has emerged.Methods: Analytical approaches involving genomics, radiomics, and pathomics were performed. Genomics studies involved both DNA and RNA analyses. DNA analyses included the patient’s tumor and germline tissues and involved targeted panel sequencing and copy number analyses. RNA analyses included tumor and adjacent normal tissues and involved studies covering expressed mutations, differential gene expression, gene fusions and molecular pathways. Radiomics approaches were utilized on clinical imaging studies and pathomics techniques were applied to tumor whole slide images.Results: A comprehensive molecular profiling endeavor involving over 50 genomic analyses corresponding to 16 sequencing datasets of this rare neoplasm of the lung were generated along with detailed radiomic and pathomic analyses to reveal insights into the etiology and molecular behavior of the patient’s tumor. Driving mutations (AKT1) and compromised tumor suppression pathways (TP53) were revealed. To ensure the accuracy and reproducibility of this study, a software infrastructure and methodology known as NPARS, which encapsulates NGS and associated data, open-source software libraries and tools including versions, and reporting features for large and complex genomic studies was used.Conclusion: Moving beyond descriptive analyses towards more functional understandings of tumor etiology, behavior, and improved therapeutic predictability requires a spectrum of quantitative molecular medicine approaches and integrations. To-date this is the most comprehensive study of a patient with PSP, which is a rare tumor of the lung. Detailed radiomic, pathomic and genomic molecular profiling approaches were performed to reveal insights regarding the etiology and molecular behavior. In the event of recurrence, a rational therapy plan is proposed based on the uncovered molecular findings.
Systemic inflammatory regulators and proliferative diabetic retinopathy: A bidirectional Mendelian randomization study
Authors: Shi Qiqin , Wang Qiangsheng , Wang Zhenqian , Lu Jiawen , Wang Ruobing 
Published: February 2023

BackgroundIncreasing evidence shows that systemic inflammation is an embedded mechanism of proliferative diabetic retinopathy (PDR). However, the specific systemic inflammatory factors involved in this process remained obscure. The study aimed to identify the upstream and downstream systemic regulators of PDR by using Mendelian randomization (MR) analyses.MethodsWe performed a bidirectional two-sample MR analysis implementing the results from genome-wide association studies for 41 serum cytokines from 8,293 Finnish individuals, and PDR from FinnGen consortium (2,025 cases vs. 284,826 controls) and eight cohorts of European ancestry (398 cases vs. 2,848 controls), respectively. The inverse-variance-weighted method was adopted as the main MR method, and four additional MR methods (MR-Egger, weighted-median, MR-pleiotropy residual sum and outlier (MR-PRESSO), and MR-Steiger filtering methods) were used for the sensitivity analyses. Results from FinnGen and eight cohorts were pooled into a meta-analysis.ResultsOur results showed that genetically predicted higher stem cell growth factor-β (SCGFb) and interleukin-8 were positively associated with an elevated risk of PDR, with a combined effect of one standard deviation (SD) increase in SCGFb and interleukin-8 causing 11.8% [95% confidence interval (CI): 0.6%, 24.2%]) and 21.4% [95% CI: 3.8%, 41.9%]) higher risk of PDR, respectively. In contrast, genetically predisposition to PDR showed a positive association with the increased levels of growth-regulated oncogene-α (GROa), stromal cell-derived factor-1 alpha (SDF1a), monocyte chemotactic protein-3 (MCP3), granulocyte colony-stimulating factor (GCSF), interleukin-12p70, and interleukin-2 receptor subunit alpha (IL-2ra).ConclusionsOur MR study identified two upstream regulators and six downstream effectors of PDR, providing opportunities for new therapeutic exploitation of PDR onset. Nonetheless, these nominal associations of systemic inflammatory regulators and PDR require validation in larger cohorts.
Anti-inflammatory effects of vagus nerve stimulation in pediatric patients with epilepsy
Authors: Kaur Supender , Selden Nathan R. , Aballay Alejandro 
Published: February 2023

IntroductionThe neural control of the immune system by the nervous system is critical to maintaining immune homeostasis, whose disruption may be an underlying cause of several diseases, including cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer’s disease.MethodsHere we studied the role of vagus nerve stimulation (VNS) on gene expression in peripheral blood mononuclear cells (PBMCs). Vagus nerve stimulation is widely used as an alternative treatment for drug-resistant epilepsy. Thus, we studied the impact that VNS treatment has on PBMCs isolated from a cohort of existing patients with medically refractory epilepsy. A comparison of genome-wide changes in gene expression was made between the epilepsy patients treated and non-treated with vagus nerve stimulation.ResultsThe analysis showed downregulation of genes related to stress, inflammatory response, and immunity, suggesting an anti-inflammatory effect of VNS in epilepsy patients. VNS also resulted in the downregulation of the insulin catabolic process, which may reduce circulating blood glucose.DiscussionThese results provide a potential molecular explanation for the beneficial role of the ketogenic diet, which also controls blood glucose, in treating refractory epilepsy. The findings indicate that direct VNS might be a useful therapeutic alternative to treat chronic inflammatory conditions.
Vaccination using mutated receptor binding domains of SARS-CoV-2: Evidence for partial immune escape but not serotype formation
Authors: Chang Xinyue , Liu Xuelan , Martina Byron , Zeltins Andris , Augusto Gilles , Vogel Monique , Mohsen Mona O. , Speiser Daniel E. , Bachmann Martin F. 
Published: February 2023

IntroductionSARS-CoV-2 has developed a number of Variants of Concern (VOC) with increased infectivity and/or reduced recognition by neutralizing antibodies specific for the receptor binding domain (RBD) of the spike protein. Extended studies of other viruses have shown that strong and broad viral escape from neutralizing serum antibodies is typically associated with the formation of serotypes.MethodsTo address the question of serotype formation for SARS-CoV-2 in detail, we generated recombinant RBDs of VOCs and displayed them on virus-like particles (VLPs) for vaccination and specific antibody responses. ResultsAs expected, mice immunized with wild type (wt) RBD generated antibodies that recognized wt RBD well but displayed reduced binding to VOC RBDs, in particular those with the E484K mutation. Unexpectedly, however, antibodies induced by the VOC vaccines typically recognized best the wt RBDs, often more than the homologous VOC RBDs used for immunization. Hence, these data do not reveal different serotypes but represent a newly observed viral evolution, suggesting a unique situation where inherent differences of RBDs are responsible for induction of neutralizing antibodies. DiscussionTherefore, besides antibody (fine) specificity, other qualities of antibodies (e.g. their affinity) determine neutralizing capability. Immune escape of SARS-CoV-2 VOCs only affects a fraction of an individual’s serum antibodies. Consequently, many neutralizing serum antibodies are cross-reactive and thus protective against multiple current and future VOCs. Besides considering variant sequences for next generation vaccines, broader protection will be achieved with vaccines that induce elevated titers of high-quality antibodies.
Genome-wide copy number variant screening of Saudi schizophrenia patients reveals larger deletions in cases versus controls
Authors: Abumadini Mahdi S. , Al Ghamdi Kholoud S. , Alqahtani Abdullah H. , Almedallah Dana K. , Callans Lauren , Jarad Jumanah A. , Cyrus Cyril , Koeleman Bobby P. C. , Keating Brendan J. , Pankratz Nathan , Al-Ali Amein K. 
Published: February 2023

IntroductionGenome-wide association studies have discovered common polymorphisms in regions associated with schizophrenia. No genome-wide analyses have been performed in Saudi schizophrenia subjects.MethodsGenome-wide genotyping data from 136 Saudi schizophrenia cases and 97 Saudi controls in addition to 4,625 American were examined for copy number variants (CNVs). A hidden Markov model approach was used to call CNVs.ResultsCNVs in schizophrenia cases were twice as large on average than CNVs in controls (p = 0.04). The analyses focused on extremely large &gt;250 kilobases CNVs or homozygous deletions of any size. One extremely large deletion was noted in a single case (16.5 megabases on chromosome 10). Two cases had an 814 kb duplication of chromosome 7 spanning a cluster of genes, including circadian-related loci, and two other cases had 277 kb deletions of chromosome 9 encompassing an olfactory receptors gene family. CNVs were also seen in loci previously associated with schizophrenia, namely a 16p11 proximal duplication and two 22q11.2 deletions.DiscussionRuns of homozygosity (ROHs) were analyzed across the genome to investigate correlation with schizophrenia risk. While rates and sizes of these ROHs were similar in cases and controls, we identified 10 regions where multiple cases had ROHs and controls did not.
GA-OH enhances the cytotoxicity of photon and proton radiation in HPV+ HNSCC cells
Authors: Chitsike Lennox , Bertucci Antonella , Vazquez Marcelo , Lee Steve , Unternaehrer Juli J. , Duerksen-Hughes Penelope J. 
Published: February 2023

IntroductionTreatment-related toxicity following either chemo- or radiotherapy can create significant clinical challenges for HNSCC cancer patients, particularly those with HPV-associated oropharyngeal squamous cell carcinoma. Identifying and characterizing targeted therapy agents that enhance the efficacy of radiation is a reasonable approach for developing de-escalated radiation regimens that result in less radiation-induced sequelae. We evaluated the ability of our recently discovered, novel HPV E6 inhibitor (GA-OH) to radio-sensitize HPV+ and HPV- HNSCC cell lines to photon and proton radiation.MethodsRadiosensitivity to either photon or proton beams was assessed using various assays such as colony formation assay, DNA damage markers, cell cycle and apoptosis, western blotting, and primary cells. Calculations for radiosensitivity indices and relative biological effectiveness (RBE) were based on the linear quadratic model.ResultsOur results showed that radiation derived from both X-ray photons and protons is effective in inhibiting colony formation in HNSCC cells, and that GA-OH potentiated radiosensitivity of the cells. This effect was stronger in HPV+ cells as compared to their HPV- counterparts. We also found that GA-OH was more effective than cetuximab but less effective than cisplatin (CDDP) in enhancing radiosensitivity of HSNCC cells. Further tests indicated that the effects of GA-OH on the response to radiation may be mediated through cell cycle arrest, particularly in HPV+ cell lines. Importantly, the results also showed that GA-OH increases the apoptotic induction of radiation as measured by several apoptotic markers, even though radiation alone had little effect on apoptosis.ConclusionThe enhanced combinatorial cytotoxicity found in this study indicates the strong potential of E6 inhibition as a strategy to sensitize cells to radiation. Future research is warranted to further characterize the interaction of GA-OH derivatives and other E6-specific inhibitors with radiation, as well as its potential to improve the safety and effectiveness of radiation treatment for patients with oropharyngeal cancer.