bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-type specific distribution and activation of type I IFN pathway molecules at the placental maternal-fetal interface in response to COVID-19 infection
Authors: Wang Yuping , Gu Yang , Lewis David F. , Gu Xin , Brown Karisa , Lachute Courtney , Hankins Miriam , Scott Rona S. , Busada Caitlin , Cooper Danielle B. , McCathran Charles E. , Barrilleaux Perry 
Published: January 2023

Background and objectiveCOVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy.MethodsExpression of IFN activation signaling pathway molecules, including cyclic GMP–AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNβ were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review.ResultsExcept BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells; IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs); and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells.ConclusionsSTING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.
Adrenal gland involvement in 11-ketotestosterone production analyzed using LC-MS/MS
Authors: Ikegawa Kento , Hasegawa Yukihiro 
Published: January 2023

Introduction11-ketotestosterone (11KT), which is derived by the bioconversion of testosterone via 11β-hydroxytestosterone (11OHT), is a potent agonist of the human androgen receptor. The adrenal gland is considered an important organ in 11KT production because CYP11B1, which catalyzes testosterone to 11OHT, is expressed in the adrenal glands. The present study aimed to demonstrate adrenal gland involvement in 11KT production in prepubertal children, a topic which has not yet been addressed by any previous studies.MethodsThree, retrospective, observational studies were performed. Study 1 enrolled patients aged 8 months to 7 years with severe Kawasaki disease (KD) who were treated with mPSL pulse. Studies 2 and 3 included patients who had received a corticotropin-releasing hormone (CRH) stimulation test and adrenocorticotropic hormone (ACTH) stimulation test, respectively. Samples were collected before and after treatment or drug administration, and serum 11KT, 11OHT, and other 11-oxygenated androgens were measured by LC-MS/MS. Steroid hormone values before and after medication were analyzed using the Wilcoxon signed rank test.ResultsStudies 1, 2, and 3 included twenty patients with severe KD, eight patients with a CRH stimulation test, and eight patients with an ACTH stimulation test, respectively. Study 1 demonstrated that the median (IQR) 11KT level was significantly higher before, than after, mPSL pulse (0.39 (0.28-0.47) nmol/L versus 0.064 (0.012-0.075) nmol/L; P &lt; 0.001). Studies 2 and 3 indicated no significant difference in the median 11KT value before and after the CRH or ACTH stimulation test while the 11OHT value was significantly higher after the test.ConclusionIn conclusion, the mediation of 11KT production by ACTH demonstrated the importance of the adrenal glands in the synthesis of this androgen in prepubertal children.
Integration of metabolomics and transcriptomics provides insights into enhanced osteogenesis in Ano5Cys360Tyr knock-in mouse model
Authors: Li Hongyu , Liu Sirui , Miao Congcong , Lv Yan , Hu Ying 
Published: January 2023

IntroductionGnathodiaphyseal dysplasia (GDD; OMIM#166260) is a rare autosomal dominant disorder characterized by diaphyseal sclerosis of tubular bones and cemento-osseous lesions in mandibles. GDD is caused by point mutations in the ANO5 gene. However, the mechanisms underlying GDD have not been disclosed. We previously generated the first knock-in mouse model for GDD expressing a human mutation (p.Cys360Tyr) in ANO5 and homozygous Ano5 knock-in (Ano5KI/KI) mice exhibited representative traits of human GDD especially including enhanced osteogenesis.MethodsMetabolomics and transcriptomics analyses were conducted for wildtype (Ano5+/+) and Ano5KI/KI mature mouse calvarial osteoblasts (mCOBs) grown in osteogenic cultures for 14 days to identify differential intracellular metabolites and genes involved in GDD. Subsequently, related differential genes were validated by qRT-PCR. Cell proliferation was confirmed by CCK8 assay and calcium content in mineral nodules was detected using SEM-EDS.ResultsMetabolomics identified 42 differential metabolites that are primarily involved in amino acid and pyrimidine metabolism, and endocrine and other factor-regulated calcium reabsorption. Concomitantly, transcriptomic analysis revealed 407 differentially expressed genes in Ano5KI/KI osteoblasts compared with wildtype. Gene ontology and pathway analysis indicated that Ano5Cys360Tyr mutation considerably promoted cell cycle progression and perturbed calcium signaling pathway, which were confirmed by validated experiments. qRT-PCR and CCK-8 assays manifested that proliferation of Ano5KI/KI mCOBs was enhanced and the expression of cell cycle regulating genes (Mki67, Ccnb1, and Ccna2) was increased. In addition, SEM-EDS demonstrated that Ano5KI/KI mCOBs developed higher calcium contents in mineral nodules than Ano5+/+ mCOBs, while some calcium-related genes (Cacna1, Slc8a1, and Cyp27b1) were significantly up-regulated. Furthermore, osteocalcin which has been proved to be an osteoblast-derived metabolic hormone was upregulated in Ano5KI/KI osteoblast cultures.DiscussionOur data demonstrated that the Ano5Cys360Tyr mutation could affect the metabolism of osteoblasts, leading to unwonted calcium homeostasis and cellular proliferation that can contribute to the underlying pathogenesis of GDD disorders.
LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
Authors: Cruz David , Rodríguez-Romanos Rocío , González-Bartulos Marta , García-Cadenas Irene , de la Cámara Rafael , Heras Inmaculada , Buño Ismael , Santos Nazly , Lloveras Natàlia , Velarde Pilar , Tuset Esperanza , Martínez Carmen , González Marcos , Sanz Guillermo F. , Ferrá Christelle , Sampol Antonia , Coll Rosa , Pérez-Simón Jose A. , López-Jiménez Javier , Jurado Manuel , Gallardo David 
Published: January 2023

IntroductionThe association of polymorphisms in molecules involved in the immune response (checkpoint inhibitors) with the clinical outcome after allogeneic transplantation (alloHSCT) has been described. Lymphocyte Activation 3 (LAG3) is a surface protein that plays a regulatory role in immunity as an inhibitory immune checkpoint molecule.MethodsTo determine its role in the alloHSCT setting, we analyzed 797 patients transplanted from HLA-identical sibling donors. The LAG3 rs870849 C&gt;T polymorphism was genotyped in donors.ResultsWe detected a higher incidence of severe acute GVHD in patients transplanted from donors with TT genotype (p: 0.047, HR 1.64; 95% CI 1.01 – 2.67). Overall survival (OS) was worse for patients transplanted from donors with the rs870849 CT/TT genotype (0.020; HR, 1.44; 95% CI 1.06 – 1.96), as well as disease-free survival (DFS) (p: 0.002; HR 1.58, 95%CI: 1.18 – 2.14) and transplant-related mortality (TRM) (p&lt; 0.001; HR: 1.88, 95% CI 1.29 – 2.74). When combining the LAG3 rs870849 and the PDCD1 rs36084323 genotypes of the donor, three genetic groups were well defined, allowing a good stratification of the risk of acute GVHD, TRM, OS and DFS.DiscussionWe conclude that the LAG3 genotype of the donor may be considered in donors’ selection. As this selection may be limited in the HLA-identical sibling donor scenario, further studies exploring the impact of LAG3 genotype of the donor in unrelated transplantation are warranted.
Litter size influences rumen microbiota and fermentation efficiency, thus determining host early growth in goats
Authors: Wang Dangdang , Tang Guangfu , Yu Junjian , Li Yuanyuan , Wang Yannan , Chen Luyu , Lei Xinjian , Cao Yangchun , Yao Junhu 
Published: January 2023

IntroductionMultiple litters are accompanied by low birth weight, low survival rates, and growth rates in goats during early life. Regulating rumen microbiota structure can indirectly or directly affect host metabolism and animal growth. However, the relationship between high litter size and rumen microbiome, rumen fermentation, and growth performance in goat kids is unclear.MethodsIn the present study, thirty 6-month-old, female goats were investigated, of which 10 goats were randomly chosen from single, twin and triplet goats respectively, and their birth weight was recorded. From birth, all goats were subjected to the same feed and management practices. Individual weaning and youth body weight were measured, and the rumen fluid samples were collected to characterize the bacterial communities and to determine the ruminal volatile fatty acids (VFA), free amino acids (AA), and free fatty acids (FA) concentration of those young goats.Results and DiscussionCompared with the single and twin goats, triplet goats have lower weaning and youth body weight and average daily gain (ADG). Ruminal propionate, butyrate, and total VFA were decreased in triplet goats. Meanwhile, ruminal AA, such as branched chain amino acids (BCAA), essential amino acids (EAA), unsaturated fatty acids (UFA), and monounsaturated fatty acids (MUFA) were decreased, while saturated fatty acids (SFA) and odd and branched chain fatty acids (OBCFA) were increased in triplet goats. Our results also revealed that litter size significantly affected the rumen bacterial communities, and triplet goats had a lower the Firmicutes: Bacteroidota ratio, the abundance of Firmicutes phylum, Rikenellaceae family, andRikenellaceae RC9 gut group, and had a higher proportion of Prevotellaceae family, and several genera of Prevotellaceae, such asPrevotella, andunclassified f Prevotellaceae. Furthermore, Spearman’s correlation network analysis showed that the changes in the rumen bacteria were associated with changes in rumen metabolites. In conclusion, this study revealed that high litter size could bring disturbances to the microbial communities and decrease the rumen fermentation efficiency and growth performance, which can be utilized to better understand variation in microbial ecology that will improve growth performance in triplet goats.
The impact of aging on morphometric changes in the cerebellum: A voxel-based morphometry study
Authors: Stalter Johannes , Yogeswaran Vinuya , Vogel Wolfgang , Sörös Peter , Mathys Christian , Witt Karsten 
Published: January 2023

IntroductionAging influences the morphology of the central nervous system. While several previous studies focused on morphometric changes of the supratentorial parts, investigations on age-related cerebellar changes are rare. The literature concerning the morphological changes in the cerebellum is heterogenous depending (i) on the methods used (cerebellar analysis in the context of a whole brain analysis or specific methods for a cerebellar analysis), (ii) the life span that was investigated, and (iii) the analytic approach (i.e., using linear or non-linear methods).MethodsWe fill this research gap by investigating age-dependent cerebellar changes in the aging process occurring before the age of 70 in healthy participants, using non-linear methods and the spatially unbiased infratentorial template (SUIT) toolbox which is specifically developed to examine the cerebellum. Furthermore, to derive an overview of the possible behavioral correlates, we relate our findings to functional maps of the cerebellum. Twenty-four older participants (mean age 64.42 years, SD ± 4.8) and 25 younger participants (mean age 24.6 years, SD ± 2.14) were scanned using a 3 T-MRI, and the resulting data were processed using a SUIT.ResultsGray matter (GM) volume loss was found in older participants in three clusters in the right cerebellar region, namely crus I/II and lobule VI related to the frontoparietal network, with crus I being functionally related to the default-mode network and lobule VI extending into vermis VIIa related to the ventral-attention-network.DiscussionOur results underline an age-related decline in GM volume in the right cerebellar regions that are functionally predominantly related to non-motor networks and cognitive tasks regions of the cerebellum before the age of 70.
Effects of acute exercise fatigue on the spatiotemporal dynamics of resting-state large-scale brain networks
Authors: Zhao Shanguang , Lin Hao , Chi Aiping , Gao Yuanyuan 
Published: January 2023

IntroductionVarious approaches have been used to explore different aspects of the regulation of brain activity by acute exercise, but few studies have been conducted on the effects of acute exercise fatigue on large-scale brain functional networks. Therefore, the present study aimed to explore the effects of acute exercise fatigue on resting-state electroencephalogram (EEG) microstates and large-scale brain network rhythm energy.MethodsThe Bruce protocol was used as the experimental exercise model with a self-controlled experimental design. Thirty males performed incremental load exercise tests on treadmill until exhaustion. EEG signal acquisition was completed before and after exercise. EEG microstates and resting-state cortical rhythm techniques were used to analyze the EEG signal.ResultsThe microstate results showed that the duration, occurrence, and contribution of Microstate C were significantly higher after exhaustive exercise (p’s &lt; 0.01). There was a significantly lower contribution of Microstate D (p &lt; 0.05), a significant increase in transition probabilities between Microstate A and C (p &lt; 0.05), and a significant decrease in transition probabilities between Microstate B and D (p &lt; 0.05). The results of EEG rhythm energy on the large-scale brain network showed that the energy in the high-frequency β band was significantly higher in the visual network (p &lt; 0.05).DiscussionOur results suggest that frequently Microstate C associated with the convexity network are important for the organism to respond to internal and external information stimuli and thus regulate motor behavior in time to protect organism integrity. The decreases in Microstate D parameters, associated with the attentional network, are an important neural mechanism explaining the decrease in attention-related cognitive or behavioral performance due to acute exercise fatigue. The high energy in the high-frequency β band on the visual network can be explained in the sense of the neural efficiency hypothesis, which indicates a decrease in neural efficiency.
Case Report: Octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma
Authors: Wang Zilong , Liu Feifan , Li Chao , Yuan Huisheng , Xiang Yuzhu , Wei Chunxiao , Zhu Dongyuan , Wang Muwen 
Published: January 2023

BackgroundMetastatic pheochromocytomas and paragangliomas are rare neuroendocrine tumors with a poor prognosis. Bladder paraganglioma concomitant with urothelial papilloma is even rarer. However, the rate of tumor response to cyclophosphamide–vincristine–dacarbazine (CVD) chemotherapy and 5-year overall survival for patients with metastatic PPGLs remained lower. We described, for the first time, a case of a patient with multiple metastatic bladder PGL who received octreotide LAR combined with CVD chemotherapy after urological surgery and then octreotide therapy was continued during follow-up.Case presentationA 43-year-old male patient was admitted to the urology department for frequent micturition syncope concomitant with malignant hypertension. Preoperative findings were elevated levels of normetanephrine in 24-h urine or plasma. CT and MRI indicated diagnosis of suspicious bladder paraganglioma. Transurethral resection of bladder tumor combined with laparoscopic partial cystectomy was performed successfully after preoperative phenoxybenzamine with aggressive volume repletion for 7 days. The result of postoperative pathology was immediate-risk functional bladder paraganglioma (T2N0M0, Stage II) concomitant with urothelial papilloma, and the immunohistochemistry results of PPGL were positive for Ki-67 (15%), SDHB, CgA, and SSTR2. The patient achieved enhanced recovery with normal urination and no syncope after surgery. However, the results of 18F-FDG and 18F-DOTATATE PET/CT found that the metastatic localizations of bladder PGLs were in the liver, lung, and bones at the 8th month after surgery. The patient received octreotide long-acting repeatable plus six courses of CVD chemotherapy for 6 months, and then octreotide therapy was continued every 3 months until now. Metastatic localizations were stable in CT scans, and vanillylmandelic acid in 24-h urine was maintained at lower levels during follow-up.ConclusionOctreotide long-acting repeatable plus CVD chemotherapy after surgery could achieve stable disease in the case with multiple metastatic bladder PGLs, and the following octreotide therapy could maintain a state of stable disease during the period of 6-month follow-up.
Breast cancer and dietary fat quality indices in Iranian women: A case–control study
Authors: Shafie Fatemeh , Tajadod Shirin , Aslany Zahra , Allahyari Pooneh , Vahdat Mahsa , Shekari Soheila , Mohseni Golsa Khalatbari , Gholamalizadeh Maryam , Mohammadi Saeideh , Bahar Bojlul , Shafaei Hanieh , Doaei Saeid 
Published: January 2023

BackgroundThe association between breast cancer (BC) and different indices of dietary fats has not been well-studied. Thus, this study aimed to investigate the association between BC and dietary fat quality (DFQ) indices in Iranian women.MethodsThis case–control study was conducted on 120 women with breast cancer and 240 healthy women in Tehran, Iran. Food Frequency Questionnaire and nutritionist IV software were used to assess the intake of dietary fats and to calculate the DFQ indices.ResultsThe patients with BC had a higher total fat (TF) (P &lt; 0.01) and a lower ratio of polyunsaturated fatty acids (PUFAs) omega-3 to PUFAs omega-6 (ω-3/ω-6) compared with the controls (P &lt; 0.001). TF had a significant association with BC risk (OR: 1.16; 95% CI: 1.01–1.33, P &lt; 0.001). No significant association was found between BC and PUFA/saturated fatty acid ratio or the ω-3/ω-6 ratio.ConclusionThe patients with BC had a lower ω-3/ω-6 ratio and a higher total dietary fat intake than the healthy women. Total dietary fat intake was also directly associated with the risk of BC. Thus, low-fat diets may have beneficial effects for BC prevention. Further longitudinal studies are warranted.
Multiomics integration reveals the effect of Orexin A on glioblastoma
Authors: Yang Sha , Huan Renzheng , Yue Jianhe , Guo Jin , Deng Mei , Wang Liya , Peng Shuo , Lin Xin , Liu Lin , Wang Jia , Han Guoqiang , Zha Yan , Liu Jian , Zhang Jiqin , Tan Ying 
Published: January 2023

Objectives: This study involved a multi-omics analysis of glioblastoma (GBM) samples to elaborate the potential mechanism of drug treatment.Methods: The GBM cells treated with or without orexin A were acquired from sequencing analysis. Differentially expressed genes/proteins/metabolites (DEGs/ DEPs/ DEMs) were screened. Next, combination analyses were conducted to investigate the common pathways and correlations between the two groups. Lastly, transcriptome-proteome-metabolome association analysis was carried out to determine the common pathways, and the genes in these pathways were analyzed through Kaplan-Meier (K-M) survival analysis in public databases. Cell and animal experiments were performed to investigate the anti-glioma activity of orexin A.Results: A total of 1,527 DEGs, 52 DEPs, and 153 DEMs were found. Moreover, the combination analyses revealed that 6, 4, and 1 common pathways were present in the transcriptome-proteome, proteome-metabolome, and transcriptome-metabolome, respectively. Certain correlations were observed between the two data sets. Finally, 11 common pathways were discovered in association analysis, and 138 common genes were screened out in these common pathways. Six genes showed significant differences in terms of survival in both TCGA and CGGA. In addition, orexin A inhibited the proliferation, migration, and invasion of glioma in vitro and in vivo.Conclusion: Eleven common KEGG pathways with six common genes were found among different omics participations, revealing the underlying mechanisms in different omics and providing theoretical basis and reference for multi-omics research on drug treatment.