bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybrid single staged treatment of coronary arteries and aorto-iliac obstruction disease: a case report
Authors: Kasama Keiichiro , Uranaka Yasuko , Tomita Hiroto , Matsumoto Atsushi , Suzuki Shinichi 
Published: March 2022

Abstract
Background
If the internal thoracic artery is a collateral circulation to the lower extremities, careful consideration should be given to its use when coronary artery bypass grafting is required. We report a case of CABG with bilateral common iliac artery lesions and collateral circulation from the bilateral ITAs on the peripheral side.

Case presentation
A 58-year-old man was admitted to our department with claudication and dyspnea upon exertion. He was diagnosed with right common iliac artery obstruction and 90% stenosis of the left common iliac artery. Coronary angiography revealed three-vessel disease with 50% stenosis of the left main trunk. The bilateral ITA showed a rich collateral flow to the lower extremities. Hybrid single staged repair with percutaneous transluminal angioplasty for the left iliac lesion was performed, followed by off-pump coronary artery bypass grafting (CABG) and femoro-femoral crossover bypass. Postoperative angiography revealed that all grafts were patent. The postoperative course was uneventful, except that the patient’s creatinine kinase level increased to 7177 U/L on postoperative day 1.

Conclusion
To treat coronary artery disease with peripheral artery disease, especially those with iliac artery occlusion lesions with collateral circulation from the ITA, not only graft selection but also the treatment strategies for peripheral lesions are considered extremely important. Hybrid single staged coronary and lower limb artery revascularization could be safely achieved by multidisciplinary team strategies.
Reductive TCA cycle catalyzed by wild-type IDH2 promotes acute myeloid leukemia and is a metabolic vulnerability for potential targeted therapy
Authors: Zeng Peiting , Lu Wenhua , Tian Jingyu , Qiao Shuang , Li Jiangjiang , Glorieux Christophe , Wen Shijun , Zhang Hui , Li Yiqing , Huang Peng 
Published: March 2022

Abstract
Background
Isocitrate dehydrogenase-2 (IDH2) is a mitochondrial enzyme that catalyzes the metabolic conversion between isocitrate and alpha-ketoglutarate (α-KG) in the TCA cycle. IDH2 mutation is an oncogenic event in acute myeloid leukemia (AML) due to the generation of 2-hydroxyglutarate. However, the role of wild-type IDH2 in AML remains unknown, despite patients with it suffer worse clinical outcome than those harboring mutant type.

Methods
IDH2 expression in AML cell lines and patient samples was evaluated by RT-qPCR, western blotting and database analyses. The role of wild-type IDH2 in AML cell survival and proliferation was tested using genetic knockdown and pharmacological inhibition in AML cells and animal models. LC–MS, GC–MS, isotope metabolic tracing, and molecular analyses were performed to reveal the underlying mechanisms.

Results
We found that wild-type IDH2 was overexpressed in AML and played a major role in promoting leukemia cell survival and proliferation in vitro and in vivo. Metabolomic analyses revealed an active IDH2-mediated reductive TCA cycle that promoted the conversion of α-KG to isocitrate/citrate to facilitate glutamine utilization for lipid synthesis in AML cells. Suppression of wild-type IDH2 by shRNA resulted in elevated α-KG and decreased isocitrate/citrate, leading to reduced lipid synthesis, a significant decrease in c-Myc downregulated by α-KG, and an inhibition of AML viability and proliferation. Importantly, pharmacological inhibition of IDH2 showed significant therapeutic effect in mice inoculated with AML cells with wt-IDH2 and induced a downregulation of C-MYC in vivo.

Conclusions
Wt-IDH2 is an essential molecule for AML cell survival and proliferation by promoting conversion of α-KG to isocitrate for lipid synthesis and by upregulating c-Myc expression and could be a potential therapeutic target in AML.
Association of recurrent mutations in BRCA1, BRCA2, RAD51C, PALB2, and CHEK2 with the risk of borderline ovarian tumor
Authors: Ogrodniczak Alicja , Menkiszak Janusz , Gronwald Jacek , Tomiczek-Szwiec Joanna , Szwiec Marek , Cybulski Cezary , Dębniak Tadeusz , Huzarski Tomasz , Tołoczko-Grabarek Aleksandra , Byrski Tomasz , Białkowska Katarzyna , Prajzendanc Karolina , Baszuk Piotr , Lubiński Jan , Jakubowska Anna 
Published: March 2022

Abstract
Background
There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs.

Methods
The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated.

Results
The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45–15.43, p=0.01).

Conclusions
Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.
Phosphorylation regulation of cardiac proteins in Babesia microti infected mice in an effort to restore heart function
Authors: Yang Xiaohong , Wang Ningmei , Ren Shuguang , Hu Yuhong , Wang Han , Ji Aimeng , Cao Lihui , Li Mengxue , Liu Jingze , Wang Hui 
Published: March 2022

Abstract
Background
Babesia is a common protozoan parasite that infects red blood cells. In mice infected with Babesia microti, the red blood cells were lysed, resulting in decreased oxygen-carrying capacity. To compensate for low blood oxygen levels, stress on the heart was greatly increased. Babesiosis induces a variety of pathologies; meanwhile, heart tissues initiate self-repair responses to babesiosis-induced tissue damage to restore heart function.

Methods
To discover the molecular mechanisms of the damage and self-repair in the heart after B. microti infection in mice, we investigated the changes in protein expression and phosphorylation modification levels in heart tissues at 0, 5, 8, 11, and 19 days post-infection using data-independent acquisition (DIA) quantitative proteomics.

Results
The numbers of global proteins we identified were 1934, 1966, 1984, 1989, and 1955 and of phosphopeptides were 5118, 5133, 5130, 5133, and 5140 at 0, 5, 8, 11, and 19 days, respectively, in heart cells after infection with B. microti. The results showed that after B. microti infection the differentially expressed proteins in mice mainly include fibrinogen α (Fgα), fibrinogen β (Fgβ), Serpina1b, Serpina1c, cathepsin Z, cytochrome c oxidases (COXs), RPS11, and RPS20. The proteins with phosphorylation changes mainly include 20-kDa light chain of myosin II (MLC20), myosin light chain kinase (MLCK), mitogen-activated protein kinase 14 (MAPK14), and Akt1. These proteins were mainly involved in coagulation processes, cell apoptosis, oxidative phosphorylation, and ribosomes.

Conclusions
The coagulation cascade-related proteins, apoptosis-related proteins, oxidative phosphorylation-related proteins, and other types of proteins are all involved in the damage and self-repair process in the heart after B. microti infection. These results offer a wealth of new targets for further exploration into the causes of heart disease induced by Babesia infection and are of great significance for novel drug development and new opportunities for targeted therapies.

Graphical Abstract
Glucose-6-Phosphate dehydrogenase deficiency associated hemolysis in a cohort of new onset type 1 diabetes children in Guangdong province, China
Authors: Xu Aijing , Jiang Minyan , Zhang Wen , Lin Yunting , Shao Yongxian , Mei Huifen , Cheng Jing , Liang Cuili , Li Cuiling , Li Xiuzhen , Liu Li 
Published: March 2022

AbstractBackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, with a high prevalence in Guangdong, China. The purpose of this study was to explore the characteristics of newly diagnosed type 1 diabetes (T1D) patients with G6PD deficiency in a cohort of Chinese children and to investigate the relationship between the diabetic ketoacidosis (DKA) and hemolysis due to G6PD deficiency in these patients.MethodsA total of 503 newly diagnosed T1D children aged 6 months–18 years were collected and their G6PD enzyme activity were measured. Fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), andG6PDgene were analysed. The pH, HCO3, and plasma osmotic pressure between DKA patients with and without hemolysis at the presentation were compared.ResultsIn the present study, G6PD deficiency accounted for 5.3% of newly diagnosed T1D children. There were no significant differences in FPG/HbA1c and HbA1c levels between T1D children alone and T1D children with G6PD deficiency. Hemolysis appeared in five of the twenty-two DKA patients with G6PD deficiency. Two patients had fever at onset and were given ibuprofen and cefazolin. The other three patients did not have infection or ingestion of hemolytic drugs. There were no significant difference in pH, HCO3, and osmotic pressure between the children with DKA with and without hemolysis at the presentation. The hemolysis occurred between 2 and 7 days after admission and the hyperglycaemia had been corrected by the time hemolysis occurs. FourG6PDgene mutations were found in the diabetes with G6PD deficiency patients: c.1376G > T, c.1388G > A, c.95A > G, and c.871G > A, all of which were genes with high frequency of G6PD deficiency in Guangdong Province. No correlation between genotype and hemolysis was found.ConclusionIn the present study, we found the frequency of G6PD deficiency among newly diagnosed T1D children was similar to that of the general population. However, DKA children with G6PD deficiency are prone to occur hemolytic anemia, and these hemolysis usually occurs when DKA is corrected and blood glucose is in homeostatic state, which is easy to be ignored. To reduce the risk of this complication, especially in areas with high incidence of G6PD deficiency, screening for G6PD activity in people with newly diagnosed diabetes should be considered.
Musculoskeletal pain and its association with health status, maturity, and sports performance in adolescent sport school students: a 2-year follow-up
Authors: Malmborg Julia S. , Bremander Ann , Bergman Stefan , Haglund Emma , Olsson M. Charlotte 
Published: March 2022

Abstract
Background
Musculoskeletal pain and its risk factors are rarely assessed in studies on adolescent athletes. The aim was to identify risk factors at baseline that were associated with the persistence or development of musculoskeletal pain at a two-year follow-up in adolescent sport school students, and to study cross-sectional associations at follow-up between musculoskeletal pain and sports performance.

Methods
Sport school students (79 boys and 52 girls, aged 14 years at baseline) were divided into infrequent (never–monthly) or frequent (weekly–almost daily) pain groups, based on frequency of pain using a pain mannequin. Logistic regression analyses were performed to study longitudinal associations between frequent pain at follow-up and baseline variables: pain group, number of regions with frequent pain, health status by EQ-5D, maturity offset (pre, average, or post peak height velocity), and sports (contact or non-contact). Linear regression analyses were used to study cross-sectional associations between pain groups and 20-m sprint, agility T-test, counter-movement jump, and grip strength at follow-up. Results were stratified by sex.

Results
A higher percentage of girls than boys reported frequent pain at follow-up (62% vs. 37%; p = 0.005). In boys, frequent pain at follow-up was associated with being pre peak height velocity at baseline (OR 3.884, CI 1.146–13.171; p = 0.029) and participating in non-contact sports (OR 3.429, CI 1.001–11.748; p = 0.050). In girls, frequent pain at follow-up was associated with having frequent pain in two or more body regions at baseline (OR 3.600, CI 1.033–12.542; p = 0.044), having a worse health status at baseline (OR 3.571, CI 1.026–12.434; p = 0.045), and participating in non-contact sports (OR 8.282, CI 2.011–34.116; p = 0.003). In boys, frequent pain was associated with worse performances in 20-m sprint and counter-movement jump, but not in agility T-test and grip strength.

Conclusions
Baseline risk factors for having frequent pain at follow-up were late maturation in boys, frequent pain and worse health status in girls, and participation in non-contact sports in both sexes. Boys with pain performed worse in sports tests. Coaches and school health-care services should pay attention to the risk factors and work towards preventing pain from becoming persistent.
The Autism Biomarkers Consortium for Clinical Trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials
Authors: Shic Frederick , Naples Adam J. , Barney Erin C. , Chang Shou An , Li Beibin , McAllister Takumi , Kim Minah , Dommer Kelsey J. , Hasselmo Simone , Atyabi Adham , Wang Quan , Helleman Gerhard , Levin April R. , Seow Helen , Bernier Raphael , Charwaska Katarzyna , Dawson Geraldine , Dziura James , Faja Susan , Jeste Shafali Spurling , Johnson Scott P. , Murias Michael , Nelson Charles A. , Sabatos-DeVito Maura , Senturk Damla , Sugar Catherine A. , Webb Sara J. , McPartland James C. 
Published: March 2022

Abstract
Background
Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD).

Methods
The Autism Biomarkers Consortium for Clinical Trials conducted a multisite, observational study of 6–11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications.

Results
All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills.

Limitations
No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts.

Conclusions
All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA’s Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.
Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells
Authors: Deng Chunhao , Zhang Zhaoying , Xu Faxiang , Xu Jiaqi , Ren Zhili , Godoy-Parejo Carlos , Xiao Xia , Liu Weiwei , Zhou Zhou , Chen Guokai 
Published: March 2022

Abstract
Background
Thyroid hormone triiodothyronine (T3) is essential for embryogenesis and is commonly used during in vitro fertilization to ensure successful implantation. However, the regulatory mechanisms of T3 during early embryogenesis are largely unknown.

Method
To study the impact of T3 on hPSCs, cell survival and growth were evaluated by measurement of cell growth curve, cloning efficiency, survival after passaging, cell apoptosis, and cell cycle status. Pluripotency was evaluated by RT-qPCR, immunostaining and FACS analysis of pluripotency markers. Metabolic status was analyzed using LC–MS/MS and Seahorse XF Cell Mito Stress Test. Global gene expression was analyzed using RNA-seq. To study the impact of T3 on lineage-specific differentiation, cells were subjected to T3 treatment during differentiation, and the outcome was evaluated using RT-qPCR, immunostaining and FACS analysis of lineage-specific markers.

Results
In this report, we use human pluripotent stem cells (hPSCs) to show that T3 is beneficial for stem cell maintenance and promotes trophoblast differentiation. T3 enhances culture consistency by improving cell survival and passaging efficiency. It also modulates cellular metabolism and promotes energy production through oxidative phosphorylation. T3 helps maintain pluripotency by promoting ERK and SMAD2 signaling and reduces FGF2 dependence in chemically defined culture. Under BMP4 induction, T3 significantly enhances trophoblast differentiation.

Conclusion
In summary, our study reveals the impact of T3 on stem cell culture through signal transduction and metabolism and highlights its potential role in improving stem cell applications.
Exendin-4 and eldecalcitol synergistically promote osteogenic differentiation of bone marrow mesenchymal stem cells through M2 macrophages polarization via PI3K/AKT pathway
Authors: Lu Yupu , Liu Shanshan , Yang Panpan , Kou Yuying , Li Congshan , Liu Hongrui , Li Minqi 
Published: March 2022

Abstract
Background
The incidence of diabetic osteoporosis is increasing. This article evaluates the effect of combination treatment with the hypoglycemic drug exendin-4 (Ex-4) and the vitamin D analog eldecalcitol (ED-71) on improving diabetic osteoporosis and explores the relevant mechanism of action.

Method
Micro-CT, HE staining, immunohistochemistry, qPCR and ELISA were used to evaluate the impact of Ex-4 and ED-71 on bone formation and macrophage polarization in a mouse model of diabetic osteoporosis in vivo. Immunofluorescence, flow cytometry and qPCR were used to characterize the polarization type of macrophages treated with Ex-4 and ED-71 in vitro. A co-culture system of BMSCs and macrophages was established. Subsequently, crystal violet staining, alkaline phosphatase staining and alizarin red staining were used to evaluate the migration and osteogenesis differentiation of BMSCs.

Results
Ex-4 combined with ED-71 significantly reduced blood glucose levels and enhanced bone formation in mice with diabetic osteoporosis. In addition, Ex-4 synergized with ED-71 to induce the polarization of macrophages into M2 through the PI3K/AKT pathway. Macrophages treated with the combination of Ex-4 and ED-71 can significantly induce the osteogenic differentiation of BMSCs.

Conclusion
Ex-4 synergized with ED-71 to reduce blood glucose levels significantly. And this combination therapy can synergistically induce osteogenic differentiation of BMSCs by promoting M2 macrophages polarization, thereby improving diabetic osteoporosis. Therefore, the combination of Ex-4 and ED-71 may be a new strategy for the treatment of diabetic osteoporosis.
StemSC: a cross-dataset human stemness index for single-cell samples
Authors: Zheng Hailong , Xie Jiajing , Song Kai , Yang Jing , Xiao Huiting , Zhang Jiashuai , Li Keru , Yuan Rongqiang , Zhao Yuting , Gu Yunyan , Zhao Wenyuan 
Published: March 2022

Abstract
Background
Stemness is defined as the potential of cells for self-renewal and differentiation. Many transcriptome-based methods for stemness evaluation have been proposed. However, all these methods showed low negative correlations with differentiation time and can’t leverage the existing experimentally validated stem cells to recognize the stem-like cells.

Methods
Here, we constructed a stemness index for single-cell samples (StemSC) based on relative expression orderings (REO) of gene pairs. Firstly, we identified the stemness-related genes by selecting the genes significantly related to differentiation time. Then, we used 13 RNA-seq datasets from both the bulk and single-cell embryonic stem cell (ESC) samples to construct the reference REOs. Finally, the StemSC value of a given sample was calculated as the percentage of gene pairs with the same REOs as the ESC samples.

Results
We validated the StemSC by its higher negative correlations with differentiation time in eight normal datasets and its higher positive correlations with tumor dedifferentiation in three colorectal cancer datasets and four glioma datasets. Besides, the robust of StemSC to batch effect enabled us to leverage the existing experimentally validated cancer stem cells to recognize the stem-like cells in other independent tumor datasets. And the recognized stem-like tumor cells had fewer interactions with anti-tumor immune cells. Further survival analysis showed the immunotherapy-treated patients with high stemness had worse survival than those with low stemness.

Conclusions
StemSC is a better stemness index to calculate the stemness across datasets, which can help researchers explore the effect of stemness on other biological processes.
Identification of differentially expressed genes and signaling pathways with Candida infection by bioinformatics analysis
Authors: Zhu Guo-Dong , Xie Li-Min , Su Jian-Wen , Cao Xun-Jie , Yin Xin , Li Ya-Ping , Gao Yuan-Mei , Guo Xu-Guang 
Published: March 2022

Abstract
Background
Opportunistic Candida species causes severe infections when the human immune system is weakened, leading to high mortality.

Methods
In our study, bioinformatics analysis was used to study the high-throughput sequencing data of samples infected with four kinds of Candida species. And the hub genes were obtained by statistical analysis.

Results
A total of 547, 422, 415 and 405 differentially expressed genes (DEGs) of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis groups were obtained, respectively. A total of 216 DEGs were obtained after taking intersections of DEGs from the four groups. A protein–protein interaction (PPI) network was established using these 216 genes. The top 10 hub genes (FOSB, EGR1, JUNB, ATF3, EGR2, NR4A1, NR4A2, DUSP1, BTG2, and EGR3) were acquired through calculation by the cytoHubba plug-in in Cytoscape software. Validated by the sequencing data of peripheral blood, JUNB, ATF3 and EGR2 genes were significant statistical significance.

Conclusions
In conclusion, our study demonstrated the potential pathogenic genes in Candida species and their underlying mechanisms by bioinformatic analysis methods. Further, after statistical validation, JUNB, ATF3 and EGR2 genes were attained, which may be used as potential biomarkers with Candida species infection.