bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the T-cell repertoire and transcriptome identifies mechanisms of regulatory T-cell suppression of GVHD
Authors: Lohmeyer Juliane K. , Hirai Toshihito , Turkoz Mustafa , Buhler Stephane , Lopes Ramos Teresa , Köhler Natalie , Baker Jeanette , Melotti Astrid , Wagner Ingrid , Pradier Amandine , Wang Sisi , Ji Xuhuai , Becattini Simone , Villard Jean , Merkler Doron , Chalandon Yves , Negrin Robert S. , Simonetta Federico 
Published: December 2022

Abstract
CD4+FOXP3+ regulatory T cells (Tregs) have demonstrated efficacy in the prevention and treatment of graft-versus-host disease (GVHD). Preclinical and clinical studies indicate that Tregs are able to protect from GVHD without interfering with the graft-versus-tumor (GVT) effect of hematopoietic cell transplantation (HCT), although the underlying molecular mechanisms are largely unknown. To elucidate Treg suppressive function during in vivo suppression of acute GVHD, we performed paired T-cell receptor (TCRα and ΤCRβ genes) repertoire sequencing and RNA sequencing analysis on conventional T cells (Tcons) and Tregs before and after transplantation in a major histocompatibility complex –mismatched mouse model of HCT. We show that both Tregs and Tcons underwent clonal restriction, and Tregs did not interfere with the activation of alloreactive Tcon clones and the breadth of their TCR repertoire but markedly suppressed their expansion. Transcriptomic analysis revealed that Tregs predominantly affected the transcriptome of CD4 Tcons and, to a lesser extent, that of CD8 Tcons, thus modulating the transcription of genes encoding pro- and anti-inflammatory molecules as well as enzymes involved in metabolic processes, inducing a switch from glycolysis to oxidative phosphorylation. Finally, Tregs did not interfere with the induction of gene sets involved in the GVT effect. Our results shed light onto the mechanisms of acute GVHD suppression by Tregs and will support the clinical translation of this immunoregulatory approach.
Synchronization and Stability of a Nonlinear Vibrating Mechanical System Characterized by Asymmetrical Piecewise Linearity
Authors: Zhang Xueliang , Li Zhenmin , Hu Wenchao , Wen Bangchun 
Published: December 2022

AbstractIn previous studies about the synchronization of vibrators, the restoring forces of springs are mainly treated as linear directly, whereas the nonlinear features are rarely considered in vibrating systems. To make up this drawback, a dynamical model of a nonlinear vibrating mechanical system with double rigid frames (RFs), driven by two vibrators, is proposed to explore the synchronization and stability of the system. In this paper, the nonlinearity is reflected in nonlinear restoring forces of springs characterized by asymmetrical piecewise linear, where the nonlinear stiffness of springs is linearized equivalently using the asymptotic method. Based on the average method and Hamilton’s principle, the theory conditions to achieve synchronization and stability of two vibrators are deduced. After the theory analyses, some numerical qualitative analyses are given to reveal the coupling dynamical characteristics of the system and the relative motion properties between two RFs. Besides, some experiments are carried out to examine the validity of the theoretical results and the correctness of the numerical analyses results. Based on the comparisons of the theory, numeric and experiment, the ideal working regions of the system are suggested. Based on the present work, some new types of vibrating equipment, such as vibrating discharging centrifugal dehydrators/conveyers/screens, can be designed.
LC-MS/MS based metabolomics and proteomics reveal candidate biomarkers and molecular mechanism of early IgA nephropathy
Authors: Zhang Di , Li Yaohan , Liang Mingzhu , Liang Yan , Tian Jingkui , He Qiang , Yang Bingxian , Jin Juan , Zhu Wei 
Published: December 2022

Abstract
Background
Immunoglobulin A nephropathy (IgAN), a globally common primary chronic glomerulopathy, is one of the leading causes of end-stage renal disease. However, the underlying mechanisms of IgAN have yet to be demonstrated. There were no adequate and reliable plasma biomarkers for clinical diagnosis, especially at the early stage. In the present study, integrative proteomics and metabolomics were aimed at exploring the mechanism of IgAN and identifying potential biomarkers.

Methods
Plasma from IgAN and healthy individuals were collected and analyzed in a randomized controlled manner. Data-independent acquisition quantification proteomics and mass spectrometry based untargeted metabolomics techniques were used to profile the differentially expressed proteins (DEPs) and differentially abundant metabolites (DAMs) between two groups and identify potential biomarkers for IgAN from health at the early stage. Disease-related pathways were screened out by clustering and function enrichment analyses of DEPs and DAMs. And the potential biomarkers for IgAN were identified through the machine learning approach. Additionally, an independent cohort was used to validate the priority candidates by enzyme-linked immunosorbent assay (ELISA).

Results
Proteomic and metabolomic analyses of IgAN plasma showed that the complement and the immune system were activated, while the energy and amino acid metabolism were disordered in the IgAN patients. PRKAR2A, IL6ST, SOS1, and palmitoleic acid have been identified as potential biomarkers. Based on the AUC value for the training and test sets, the classification performance was 0.994 and 0.977, respectively. The AUC of the external validation of the four biomarkers was 0.91.

Conclusion
In this study, we combined proteomics and metabolomics techniques to analyze the plasma of IgAN patients and healthy individuals, constructing a biomarker panel, which could provide new insights and provide potential novel molecular diagnoses for IgAN.
OsSAP6 Positively Regulates Soda Saline–Alkaline Stress Tolerance in Rice
Authors: Zhu Fengjin , Wang Kai , Li Danni , Liu Ziang , Li Minghui , Wang Zhenyu , Li Xiufeng , Lan Xingguo , Guan Qingjie 
Published: December 2022

Abstract
Background
Soil salinization is a worldwide environmental problem, especially in the arid and semiarid regions of northeastern China, which are heavily affected by soda saline–alkaline stress. At present, there is an urgent need to improve the soda saline–alkaline stress tolerance of rice.

Results
Stress-associated proteins are involved in regulating the abiotic stresses in plants. There are 18 members of the rice stress-associated protein (OsSAP) gene family. In this study, the expression levels of OsSAP6 in leaves and roots were upregulated with increasing NaHCO3 stress duration. OsSAP6 was located in nucleus and cytoplasm. The bud length and total root length of OsSAP6 overexpression rice were significantly longer than those of Lj11 (Oryza sativa longjing11) during germination stage, and the survival rates, plant height and malondialdehyde content at the seedling stage showed tolerance growth of saline–alkaline stress. The expression of OsCu/Zn-SOD, OsAPX2, and OsCAT1 in transgenic lines was increased significantly under SAE (soda saline–alkali soil eluent) stress. OsSAP6 interacts with OsPK5 according to yeast two-hybrid screening and luciferase complementation experiments. The expression of OsPK5 increased under NaHCO3 and H2O2 stress, and the overexpression of OsPK5 in rice improved soda saline–alkaline tolerance.

Conclusion
Overexpression of OsSAP6 in rice significantly enhanced saline–alkaline tolerance compared with the wild type. It is speculated that OsSAP6 responds to soda salinity stress and interacts with OsPK5 to positively regulate soda saline–alkaline tolerance through ROS homeostasis. This study revealed the features of OsSAP6 involved in response to soda saline–alkaline stress and the interaction with OsPK5, which provided resources for breeding aimed at improving the soda saline–alkaline stress tolerance of rice.
Deciphering the role of RNA structure in translation efficiency
Authors: Lin Jianan , Chen Yang , Zhang Yuping , Lin Haifan , Ouyang Zhengqing 
Published: December 2022

Abstract
Background
RNA secondary structure has broad impact on the fate of RNA metabolism. The reduced stability of secondary structures near the translation initiation site/start codon of the coding region promotes the efficiency of translation in both prokaryotic and eukaryotic species. However, the inaccuracy of in silico folding and the focus on the coding region limit our understanding of the global relationship between the whole mRNA structure and translation efficiency. Leveraging high-throughput RNA structure probing data in the transcriptome, we aim to systematically investigate the role of RNA structure in regulating translation efficiency.

Results
Here, we analyze the influences of hundreds of sequence and structural features on translation efficiency in the mouse embryonic stem cells (mESCs) and zebrafish developmental stages. Our findings reveal that overall in vivo RNA structure has a higher relative importance in predicting translation efficiency than in vitro RNA structure in both mESCs and zebrafish. Also, RNA structures in 3’ untranslated region (UTR) have much stronger influence on translation efficiency compared to those in coding regions or 5' UTR. Furthermore, strong alternation between in vitro and in vivo structures in 3' UTR are detected in highly translated mRNAs in mESCs but not zebrafish. Instead, moderate alteration between in vitro and in vivo RNA structures in the 5’ UTR and proximal coding regions are detected in highly translated mRNAs in zebrafish.

Conclusions
Our results suggest the openness of the 3’ UTR promotes the translation efficiency in both mice and zebrafish, with the in vivo structure in 3’ UTR more important in mice than in zebrafish. This reveals a novel role of RNA secondary structure on translational regulation.
Comparative epigenomics by machine learning approach for neuroblastoma
Authors: Sugino Ryuichi P. , Ohira Miki , Mansai Sayaka P. , Kamijo Takehiko 
Published: December 2022

Abstract
Background
Neuroblastoma (NB) is the second most common pediatric solid tumor. Because the number of genetic mutations found in tumors are small, even in some patients with unfavorable NB, epigenetic variation is expected to play an important role in NB progression. DNA methylation is a major epigenetic mechanism, and its relationship with NB prognosis has been a concern. One limitation with the analysis of variation in DNA methylation is the lack of a suitable analytical model. Therefore, in this study, we performed a random forest (RF) analysis of the DNA methylome data of NB from multiple databases.

Results
RF is a popular machine learning model owing to its simplicity, intuitiveness, and computational cost. RF analysis identified novel intermediate-risk patient groups with characteristic DNA methylation patterns within the low-risk group. Feature selection analysis based on probe annotation revealed that enhancer-annotated regions had strong predictive power, particularly for MYCN-amplified NBs. We developed a gene-based analytical model to identify candidate genes related to disease progression, such as PRDM8 and FAM13A-AS1. RF analysis revealed sufficient predictive power compared to other machine learning models.

Conclusions
RF is a useful tool for DNA methylome analysis in cancer epigenetic studies, and has potential to identify a novel cancer-related genes.
Identification of quantitative trait loci (QTL) and meta-QTL analysis for kernel size-related traits in wheat (Triticum aestivum L.)
Authors: Ma Jingfu , Liu Yuan , Zhang Peipei , Chen Tao , Tian Tian , Wang Peng , Che Zhuo , Shahinnia Fahimeh , Yang Delong 
Published: December 2022

Abstract
Background
Kernel size-related traits, including kernel length (KL), kernel width (KW), kernel diameter ratio (KDR) and kernel thickness (KT), are critical determinants for wheat kernel weight and yield and highly governed by a type of quantitative genetic basis. Genome-wide identification of major and stable quantitative trait loci (QTLs) and functional genes are urgently required for genetic improvement in wheat kernel yield. A hexaploid wheat population consisting of 120 recombinant inbred lines was developed to identify QTLs for kernel size-related traits under different water environments. The meta-analysis and transcriptome evaluation were further integrated to identify major genomic regions and putative candidate genes.

Results
The analysis of variance (ANOVA) revealed more significant genotypic effects for kernel size-related traits, indicating the moderate to high heritability of 0.61–0.89. Thirty-two QTLs for kernel size-related traits were identified, explaining 3.06%—14.2% of the phenotypic variation. Eleven stable QTLs were detected in more than three water environments. The 1103 original QTLs from the 34 previous studies and the present study were employed for the MQTL analysis and refined into 58 MQTLs. The average confidence interval of the MQTLs was 3.26-fold less than that of the original QTLs. The 1864 putative candidate genes were mined within the regions of 12 core MQTLs, where 70 candidate genes were highly expressed in spikes and kernels by comprehensive analysis of wheat transcriptome data. They were involved in various metabolic pathways, such as carbon fixation in photosynthetic organisms, carbon metabolism, mRNA surveillance pathway, RNA transport and biosynthesis of secondary metabolites.

Conclusions
Major genomic regions and putative candidate genes for kernel size-related traits in wheat have been revealed by an integrative strategy with QTL linkage mapping, meta-analysis and transcriptomic assessment. The findings provide a novel insight into understanding the genetic determinants of kernel size-related traits and will be useful for the marker-assisted selection of high yield in wheat breeding.
Time to trimethoprim/sulfamethoxazole initiation among patients with rheumatic disease complicated by Pneumocystis jirovecii pneumonia: impact on 90-day mortality
Authors: Song Siyang , Zhang Yang , Yu Jie , Xie Cuiying , Chen Yi , Zhang Xingyu 
Published: December 2022

Abstract
Background
Pneumocystis jirovecii pneumonia (PJP) is a life-threatening disease with increasing prevalence in patients with rheumatic disease. Trimethoprim/sulfamethoxazole (TMP/SMX) is an effective treatment for patients with rheumatic disease hospitalized for PJP. This study aimed to describe the 90-day mortality of patients with rheumatic disease complicated by PJP and investigate whether the administration of TMP/SMX after 7 days from initial symptoms correlates with 90-day mortality.

Methods
We enrolled consecutive patients with rheumatic disease complicated with PJP in our center from August 2018 to August 2021. The participants were classified into two groups according to when TMP/SMX was initiated: early (within the first 7 days) and late (after 7 days). The primary outcome was 90-day PJP-related mortality. Multivariate cox regression and Kaplan–Meier survival analyses were conducted to identify the risk factors for mortality and examine differences in survival between early and late use of TMP/SMX.

Results
Thirty-seven patients with rheumatic disease (median age 50.1 years, 24.3% male) complicated by PJP were enrolled in our study, and 15 (40.5%) patients died at or before 90 days of follow-up. The most common comorbidity was systemic lupus erythematosus (14, 37.8%), followed by inflammatory myopathy (11, 27.9%). Patients in the early group were less likely to require mechanical ventilation (8/27, 29.6% vs. 9/10, 90.0%, P = 0.002), lower doses glucocorticoids (43.2 mg/d vs. 72.2 mg/d, P = 0.039) and had lower mortality (7/27, 25.9% vs. 8/10, 80.0%, P = 0.006) than those in the late group. In the Kaplan–Meier analysis, the survivor probability of the early group was notably higher than that of the late group (P = 0.007). Multivariate cox regression analysis showed that initiation of TMP/SMX after 7 days from admission (hazard ratio [HR]: 5.9, 95% confidence interval [CI]: 1.1–30.4; P = 0.034) and a higher level of lactate dehydrogenase (LDH; HR: 6.0, 95% CI: 1.1–31.8; P = 0.035) were associated with 90-day mortality in patients with rheumatic disease complicated by PJP.

Conclusion
Patients with rheumatic disease complicated by PJP had poor prognoses, with mortality rates as high as 40.5%. TMP/SMX initiation after 7 days from initial symptoms and a higher level of serum LDH were significantly associated with increased 90-day mortality.
A radiomic model to classify response to neoadjuvant chemotherapy in breast cancer
Authors: McAnena Peter , Moloney Brian M. , Browne Robert , O’Halloran Niamh , Walsh Leon , Walsh Sinead , Sheppard Declan , Sweeney Karl J. , Kerin Michael J. , Lowery Aoife J. 
Published: December 2022

AbstractBackgroundMedical image analysis has evolved to facilitate the development of methods for high-throughput extraction of quantitative features that can potentially contribute to the diagnostic and treatment paradigm of cancer. There is a need for further improvement in the accuracy of predictive markers of response to neo-adjuvant chemotherapy (NAC). The aim of this study was to develop a radiomic classifier to enhance current approaches to predicting the response to NAC breast cancer.MethodsData on patients treated for breast cancer with NAC prior to surgery who had a pre-NAC dynamic contrast enhanced breast MRI were included. Response to NAC was assessed using the Miller–Payne system on the excised tumor. Tumor segmentation was carried out manually under the supervision of a consultant breast radiologist. Features were selected using least absolute shrinkage selection operator regression. A support vector machine learning model was used to classify response to NAC.Results74 patients were included. Patients were classified as having a poor response to NAC (reduction in cellularity < 90%, n = 44) and an excellent response (> 90% reduction in cellularity, n = 30). 4 radiomics features (discretized kurtosis, NGDLM contrast, GLZLM_SZE and GLZLM_ZP) were identified as pertinent predictors of response to NAC. A SVM model using these features stratified patients into poor and excellent response groups producing an AUC of 0.75. Addition of estrogen receptor status improved the accuracy of the model with an AUC of 0.811.ConclusionThis study identified a radiomic classifier incorporating 4 radiomics features to augment subtype based classification of response to NAC in breast cancer.
Improving awareness of kidney function through electronic urine output monitoring: a comparative study
Authors: Murad Omar , Orjuela Cruz Daniel F , Goldman Aliza , Stern Tal , van Heerden Peter Vernon 
Published: December 2022

Abstract
Background
The current classification for acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria integrates both serum creatinine (SCr) and urine output (UO). Most reports on AKI claim to use KDIGO guidelines but fail to include the UO criterion. It has been shown that patients who had intensive UO monitoring, with or without AKI, had significantly less cumulative fluid volume and fluid overload, reduced vasopressor use, and improved 30-day mortality. We examined whether real-time monitoring of this simple, sensitive, and easy-to-use biomarker in the ICU led to more appropriate intervention by healthcare providers and better outcomes.

Methods
RenalSense Clarity RMS Consoles were installed in the General ICU at the Hadassah Medical Center, Israel, from December 2019 to November 2020. The Clarity RMS system continuously and electronically monitors UO in real-time. 100 patients were randomly selected from this period as the study group (UOelec) and compared to a matched control group (UOmanual) from the same period two years earlier. To test whether there was an association between oliguric hours and fluid treatment in each group, the correlation was calculated and analyzed for each of the different UO monitoring methods.

Results
Therapeutic intervention: The correlation of the sum of all oliguric hours on Day 1 and 2 with the sum of any therapeutic intervention (fluid bolus or furosemide) showed a significant correlation for the study group UOelec (P = 0.017). The matched control group UOmanual showed no such correlation (P = 0.932). Length of Stay (LOS): Median LOS [IQR] in the ICU of UOelec versus UOmanual was 69.46 [44.7, 125.9] hours and 116.5 [62.46, 281.3] hours, respectively (P = 0.0002).

Conclusions
The results of our study strongly suggest that ICU patients had more meaningful and better medical intervention, and improved outcomes, with electronic UO monitoring than with manual monitoring.
Construction and validation of the Oxford Neurodevelopment Assessment (OX-NDA) in 1-year-old Brazilian children
Authors: Fernandes Michelle , Bassani Diego , Albernaz Elaine , Bertoldi Andrea D. , Silveira Mariangela F. , Matijsevich Alicia , Anselmi Luciana , Cruz Suélen , Halal Camila S. , Tovo-Rodrigues Luciana , Cruz Gloria Isabel Nino , Metgud Deepa , Santos Ina S. 
Published: December 2022

Abstract
Background
Over 250 million children under 5 years, globally, are at risk of developmental delay. Interventions during the first 2 years of life have enduring positive effects if children at risk are identified, using standardized assessments, within this window. However, identifying developmental delay during infancy is challenging and there are limited infant development assessments suitable for use in low- and middle-income (LMIC) settings. Here, we describe a new tool, the Oxford Neurodevelopment Assessment (OX-NDA), measuring cognition, language, motor, and behaviour, outcomes in 1-year-old children. We present the results of its evaluation against the Bayley Scales of Infant Development IIIrd edition (BSID-III) and its psychometric properties.

Methods
Sixteen international tools measuring infant development were analysed to inform the OX-NDA’s construction. Its agreement with the BSID-III, for cognitive, motor and language domains, was evaluated using intra-class correlations (ICCs, for absolute agreement), Bland-Altman analyses (for bias and limits of agreement), and sensitivity and specificity analyses (for accuracy) in 104 Brazilian children, aged 12 months (SD 8.4 days), recruited from the 2015 Pelotas Birth Cohort Study. Behaviour was not evaluated, as the BSID-III’s adaptive behaviour scale was not included in the cohort’s protocol. Cohen’s kappas and Cronbach’s alphas were calculated to determine the OX-NDA’s reliability and internal consistency respectively.

Results
Agreement was moderate for cognition and motor outcomes (ICCs 0.63 and 0.68, p < 0.001) and low for language outcomes (ICC 0.30, p < 0.04). Bland-Altman analysis showed little to no bias between measures across domains. The OX-NDA’s sensitivity and specificity for predicting moderate-to-severe delay on the BSID-III was 76, 73 and 43% and 75, 80 and 33% for cognition, motor and language outcomes, respectively. Inter-rater (k = 0.80-0.96) and test-rest (k = 0.85-0.94) reliability was high for all domains. Administration time was < 20 minutes.

Conclusion
The OX-NDA shows moderate agreement with the BSID-III for identifying infants at risk of cognitive and motor delay; agreement was low for language delay. It is a rapid, low-cost assessment constructed specifically for use in LMIC populations. Further work is needed to evaluate its use (i) across domains in populations beyond Brazil and (ii) to identify language delays in Brazilian children.