bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bilateral multifocality is an independent predictor of patients’ outcome in Middle Eastern papillary thyroid carcinoma
Authors: Parvathareddy Sandeep Kumar , Siraj Abdul K. , Annaiyappanaidu Padmanaban , Siraj Nabil , Al-Sobhi Saif S. , Al-Dayel Fouad , Al-Kuraya Khawla S. 
Published: January 2023

BackgroundTumor multifocality is frequently seen in Papillary thyroid carcinoma (PTC). However, few studies have analysed the impact of bilateral multifocality in PTC. The incidence of bilateral multifocality, its clinico-pathological associations and prognostic impact in PTC from Middle Eastern ethnicity remains unestablished.MethodsWe retrospectively evaluated 1283 patients who underwent total thyroidectomy for PTC. Bilateral and unilateral multifocality were decided based on the final pathology result. Primary outcome was recurrence free survival (RFS). Risk factors for bilateral multifocality were analyzed by multivariate logistic regression analysis.ResultsMultifocal PTC was found in 54.3% (697/1283) of patients. Among the 697 multifocal PTCs, 210 patients (30.1%) had unilateral multifocal PTC and 487 patients (69.9%) had bilateral multifocality. Bilateral multifocality was significantly associated with older age at diagnosis (p = 0.0263), male gender (p = 0.0201), gross extrathyroidal extension (p = 0.0332), larger primary tumor size (&gt;4cm; p = 0.0002), lateral lymph node metastasis (p = 0.0008), distant metastasis at diagnosis (p = 0.0195) and recurrence (p = 0.0001). Bilateral multifocality was also found to be an independent predictor of RFS (Hazard ratio = 1.60; 95% Confidence Interval = 1.05 – 2.55; p = 0.0300). Multivariate logistic regression analysis demonstrated tumor diameter &gt;4cm to be the only independent risk factors for bilaterality in multifocal PTC (Odds ratio = 1.86; 95% Confidence Interval = 1.13 – 3.07; p = 0.0155).ConclusionsIncidence of bilateral multifocality is high in Middle Eastern PTC. Tumor diameter &gt;4cm can be considered as a predictive factor for bilateral multifocal PTC. Bilateral multifocality appears to be an important prognostic factor for PTC and an independent predictor of RFS. Therefore, patients with bilateral multifocal PTC may benefit from more frequent follow-up to identify recurrences earlier.
Ontogeny of ependymoglial cells lining the third ventricle in mice
Authors: Lopez-Rodriguez David , Rohrbach Antoine , Lanzillo Marc , Gervais Manon , Croizier Sophie , Langlet Fanny 
Published: January 2023

IntroductionDuring hypothalamic development, the germinative neuroepithelium gives birth to diverse neural cells that regulate numerous physiological functions in adulthood.MethodsHere, we studied the ontogeny of ependymal cells in the mouse mediobasal hypothalamus using the BrdU approach and publicly available single-cell RNAseq datasets.ResultsWe observed that while typical ependymal cells are mainly produced at E13, tanycyte birth depends on time and subtypes and lasts up to P8. Typical ependymocytes and β tanycytes are the first to arise at the top and bottom of the dorsoventral axis around E13, whereas α tanycytes emerge later in development, generating an outside-in dorsoventral gradient along the third ventricle. Additionally, α tanycyte generation displayed a rostral-to-caudal pattern. Finally, tanycytes mature progressively until they reach transcriptional maturity between P4 and P14.DiscussionAltogether, this data shows that ependyma generation differs in time and distribution, highlighting the heterogeneity of the third ventricle.
Analysis of the epidemiological status, microbiology, treatment methods and financial burden of hematogenous osteomyelitis based on 259 patients in Northwest China
Authors: Lu Shuaikun , Wang Linhu , Luo Wen , Wang Guoliang , Zhu Zhenfeng , Liu Yunyan , Gao Hao , Fu Congxiao , Ren Jun , Zhang Yunfei , Zhang Yong 
Published: January 2023

BackgroundThe incidence of hematogenous osteomyelitis is on the rise, and the prognosis is poor. There has been no large-scale epidemiological analysis of hematogenous osteomyelitis in the world, and the treatment method is still controversial.MethodsA retrospective case study method was used to collect and analyze clinical data obtained from patients with hematogenous osteomyelitis in a tertiary hospital in Northwest China from January 1, 2011, to December 31, 2020. The aim of this study was to investigate the epidemiological status, microbiological characteristics, treatment and financial burden of hematogenous osteomyelitis in Northwest China to explore the therapeutic effects of different treatment methods, elucidate the epidemiological characteristics of hematogenous osteomyelitis and to provide a basis for the choice of treatment.ResultsWe included 259 patients with hematogenous osteomyelitis, including 96 patients with acute hematogenous osteomyelitis and 163 patients with chronic hematogenous osteomyelitis. The cause of the disease was not obvious in most patients, the sex ratio of males to females was 1.98, and the three most common infected sites were the tibia, femur and phalanx. Regarding preoperative serum inflammatory markers, the rate of positivity for ESR was the highest at 67.58%. Among pathogenic microorganisms, Staphylococcus aureus was the most common. Regarding the financial burden, the median total cost per patient was 25,754 RMB, and medications accounted for the largest proportion of the main costs.ConclusionsThe most common pathogen associated with HO infection was MSSA. Oxacillin has good PK and PD and is recommended as the first-line drug. Some blood-borne bone infections may lead to complications, such as pulmonary infection through bacteremia, which requires early detection to avoid a missed diagnosis. Regarding surgical intervention, debridement plus absorbable calcium sulfate bone cement and calcium sulfate calcium phosphate bone cement exclusion have achieved good therapeutic effects, but they are worthy of further in-depth research. Regarding the financial burden, the median total cost per patient was 25,754 RMB. The financial burden of blood-borne osteomyelitis was lower than that of traumatic osteomyelitis. Among the main costs, drugs accounted for the largest proportion.
Effect of calcium ionophore (A23187) on embryo development and its safety in PGT cycles
Authors: Zhang Junya , Yao Guidong , Zhang Tongwei , Hu Jingyi , Yang Guang , He Jiahuan , He Qina , Fan Huiying , Bai Yucheng , Sun Yingpu 
Published: January 2023

BackgroundIntracytoplasmic sperm injection (ICSI) has tremendous advantages for resolving the problem of male infertility. However, ICSI fertilization can fail in some patients because of various reasons, primarily because of the failure of oocyte activation. Oocytes have been activated using calcium ionophore (A23187) in previous clinical cases of ICSI fertilization failure. However, studies on the efficiency of calcium ionophore (A23187) activation, its effects on the developmental potential of embryos, and its effects on pregnancy outcomes after embryo transfer are relatively limited.MethodsIn this study, we investigated the safety and long-term efficacy of calcium ionophore (A23187) by analyzing its effects on fertilization, embryonic development, aneuploidy, and pregnancy outcomes in patients undergoing preimplantation genetic testing (PGT) cycles.ResultsComparative analyses of the activation followed by PGT (A-PGT) and PGT groups revealed no significant differences between the oocyte cleavage rate and high-quality embryo rate (98.19% vs. 98.63% and 63.13% vs. 68.39%, respectively, p &gt; 0.05). Although the blastocyst formation rate was significantly lower in the A-PGT group than that in the PGT group (52.22% vs. 59.90%, p &lt; 0.05), no significant difference was observed in the blastocyst aneuploidy rates of the two groups (24.49% vs. 24.55%, p &gt; 0.05). Furthermore, no significant differences were observed between the two groups in terms of the live birth rate (43.75% vs. 52.99%), week of delivery, and birth weight of the infants after transfer of euploid blastocysts (p &gt; 0.05). Furthermore, the 2PN rate, oocyte cleavage rate, blastocyst formation rate, and live birth rate were found to be significantly lower in the A-ICSI group than those in the ICSI group (p &lt; 0.01), but there was no significant difference between the two groups in the week of delivery and birth weight of live births (p &gt; 0.05).DiscussionThese results suggest that the use of calcium ionophore (A23187) activation as an option in cases of ICSI fertilization failure does not affect the ploidy of developing blastocysts and has no significant effects on the week of delivery or birth weight after transfer. Thus, we provide a scientific basis for the clinical safety of oocyte activation using calcium ionophore (A23187).
Using publicly available datasets to identify population-based transcriptomic landscape contributing to the aggressiveness of breast cancer in young women
Authors: Tabbal Marah , Hachim Mahmood Y. , Jan Reem Kais , Adrian Thomas E. 
Published: January 2023

Introduction: Although the risk of breast cancer increases with advancing age, some regions have larger number of young breast cancer patients (≤45 years-old), such as the Middle East, Eastern Asia, and North Africa, with more aggressive and poorly differentiated tumors. We aimed to conduct an in-silico analysis in an attempt to understand the aggressive nature of early-onset breast cancer, and to identify potential drivers of early-onset breast cancer using gene expression profiling datasets in a population-dependent manner.Methods: Functional genomics experiments data were acquired from cBioPortal database for cancer genomics, followed by the stratification of patients based on the age at representation of breast cancer and race. Differential gene expression analysis and gene amplification status analysis were carried out, followed by hub gene, transcription factor, and signalling pathway identification.Results: PAM50 subtype analysis revealed that young patients (≤45 years-old) had four-fold more basal tumors and worst progression-free survival (median of 101 months), compared with the 45–65 years group (median of 168 months). Fourteen genes were amplified in more than 14% of patients with an early-onset breast cancer. Interestingly, FREM2, LINC00332, and LINC00366 were exclusively amplified in younger patients. Gene expression data from three different populations (Asian, White, and African) revealed a unique transcriptomic profile of young patients, which was also reflected on the PAM50 subtype analysis. Our data indicates a higher tendency of young African patients to develop basal tumors, while young Asian patients are more prone to developing Luminal A tumors. Most genes that were found to be upregulated in younger patients are involved in important signaling pathways that promote cancer progression and metastasis, such as MAPK pathway, Reelin pathway and the PI3K/Akt pathway.Conclusion: This study provides strong evidence that the molecular profile of tumors derived from young breast cancer patients of different populations is unique and may explain the aggressiveness of these tumors, stressing the need to conduct population- based multi-omic analyses to identify the potential drivers for tumorigenesis and molecular profiles of young breast cancer patients.
Untargeted metabolomics reveals the effect of rearing systems on bone quality parameters in chickens
Authors: Li Dongfeng , Wu Yongfu , Shi Kai , Shao Minghui , Duan Ying , Yu Minli , Feng Chungang 
Published: January 2023

The objective of this study was to investigate the effects of rearing systems on the bone quality parameters in chickens using a metabolomics strategy. A total of 419 male one-day-old chicks were randomly allocated to two groups, a floor rearing group (FRG, n = 173) and a cage rearing group (CRG, n = 246). At 6, 8, 10, and 12 weeks of age, all chickens were radiographed by a digital X-ray machine, and body weight was recorded. At 12 weeks of age, 12 birds were selected from each group to obtain tibia and femur, and bone quality parameters of bone mineral density (BMD), mineral content (BMC), breaking strength (BBS), stiffness, Young’s modulus (YM), ash content, calcium content, and phosphorus content were determined. An untargeted metabolomics assay was performed to identify changes in the serum metabolic profile (n = 8 birds/group). The results showed that cage-reared chickens had wider tibiae and greater body weight compared with floor-reared chickens. There were no significant differences in BMC or BBS between the two groups (p &gt; 0.05), but BMD, ash content, calcium content, and phosphorus content of the tibia and femur of FRG were significantly higher than those of CRG (p &lt; 0.05). Greater stiffness and YM of the femur were also observed in birds raised in the FRG compared with those raised in the CRG (p &lt; 0.05). Taken together, the results suggest that rearing systems affected bone quality parameters. Furthermore, 148 and 149 differential metabolites were identified in positive and negative ion modes by LC-MS/MS analysis, among which 257 metabolites were significantly correlated with 16 bone quality parameters, including leucine, myristoleic acid, glycocholic acid, and N-phenylacetamide. KEGG analysis indicated that 15 metabolic pathways, including six pathways of amino acid metabolism, two pathways of lipid metabolism, and two pathways of carbohydrate metabolism, were responsible for bone quality. Overall, the present study demonstrated the effect of rearing systems on bone quality parameters, and identified several metabolites and metabolic pathways associated with bone quality parameters.
Immune-related gene signature to predict TACE refractoriness in patients with hepatocellular carcinoma based on artificial neural network
Authors: Xu Qingyu , Wang Chendong , Yin Guowen 
Published: January 2023

Background: Transarterial chemoembolization (TACE) is the standard treatment option for intermediate-stage hepatocellular carcinoma (HCC), while response varies among patients. This study aimed to identify novel immune-related genes (IRGs) and establish a prediction model for TACE refractoriness in HCC patients based on machine learning methods.Methods: Gene expression data were downloaded from GSE104580 dataset of Gene Expression Omnibus (GEO) database, differential analysis was first performed to screen differentially expressed genes (DEGs). The least absolute shrinkage and selection operator (LASSO) regression analysis was performed to further select significant DEGs. Weighted gene co-expression network analysis (WGCNA) was utilized to build a gene co-expression network and filter the hub genes. Final signature genes were determined by the intersection of LASSO analysis results, WGCNA results and IRGs list. Based on the above results, the artificial neural network (ANN) model was constructed in the training cohort and verified in the validation cohort. Receiver operating characteristics (ROC) analysis was used to assess the prediction accuracy. Correlation of signature genes with tumor microenvironment scores, immune cells and immune checkpoint molecules were further analyzed. The tumor immune dysfunction and exclusion (TIDE) score was used to evaluate the response to immunotherapy.Results: One hundred and forty-seven samples were included in this study, which was randomly divided into the training cohort (n = 103) and validation cohort (n = 44). In total, 224 genes were identified as DEGs. Further LASSO regression analysis screened out 25 genes from all DEGs. Through the intersection of LASSO results, WGCNA results and IRGs list, S100A9, TREM1, COLEC12, and IFIT1 were integrated to construct the ANN model. The areas under the curves (AUCs) of the model were .887 in training cohort and .765 in validation cohort. The four IRGs also correlated with tumor microenvironment scores, infiltrated immune cells and immune checkpoint genes in various degrees. Patients with TACE-Response, lower expression of COLEC12, S100A9, TREM1 and higher expression of IFIT1 had better response to immunotherapy.Conclusion: This study constructed and validated an IRG signature to predict the refractoriness to TACE in patients with HCC, which may have the potential to provide insights into the TACE refractoriness in HCC and become the immunotherapeutic targets for HCC patients with TACE refractoriness.
Effect of maternity waiting homes use on maternal and perinatal birth outcomes and its challenges in Amhara region, Northwest Ethiopia
Authors: Molla Muluye , Tesfa Mulugeta , Alle Atsede , Molla Firehiwot , Aschale Abiot , Endalew Bekalu , Gietaneh Wodaje 
Published: January 2023

BackgroundWomen's death due to complications of pregnancy and childbirth is still high. Maternity waiting homes are one of the strategies to reduce it. However, there is limited evidence on the effect of using maternity waiting homes on birth outcomes, particularly in this study area. Therefore, this study was aimed to estimate the effect of staying in maternity waiting homes use on maternal and perinatal birth outcomes and its challenges in the Amhara region, Northwest Ethiopia 2018.MethodsInstitutional-based comparative cross-sectional study using both quantitative and qualitative approaches was conducted. Data were collected using structured questionnaire interviews, in-depth interview and chart reviews. Propensity score matching analysis was used to estimate the effect of maternity waiting homes use on birth outcomes. Propensity score matching analysis was used to match potential differences in background characteristics that affect pregnancy outcomes between comparison groups. We used thematic analysis for qualitative data.ResultA total of 548 pregnant mothers (274 stayed in maternity waiting homes 274 did not stay) took part in this study. The proportion of adverse birth outcomes of mothers who stayed in maternity waiting homes were 15(5.5%) which is lower than those who didn't stay 35 (12.8%). After matching with baseline covariates, mean difference of adverse maternal birth outcomes, the difference between didn't use maternity waiting home and used was 10.4%, at (t = 3.78) at 5% level of significance. Similarly, the mean adverse perinatal birth outcomes difference between mothers who didn't use MWHs and used was 11% (t = 4.33).ConclusionsMaternity waiting home showed a significant positive effect on birth outcomes. Mothers who stayed in the maternity waiting homes had low adverse maternal and perinatal birth outcomes compared to non-users. Accommodations and quality health care services were the challenges mothers faced during their stay in the maternity waiting homes. Therefore, all concerned bodies should give attention accordingly to maternity waiting home services to reduce adverse birth outcomes through the strengthening of the quality of health care provided.
Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape
Authors: Oliveira Jamille Ramos , Ruiz Cesar Manuel Remuzgo , Machado Rafael Rahal Guaragna , Magawa Jhosiene Yukari , Daher Isabela Pazotti , Urbanski Alysson Henrique , Schmitz Gabriela Justamante Händel , Arcuri Helen Andrade , Ferreira Marcelo Alves , Sasahara Greyce Luri , de Medeiros Giuliana Xavier , Júnior Roberto Carlos Vieira Silva , Durigon Edison Luiz , Boscardin Silvia Beatriz , Rosa Daniela Santoro , Schechtman Deborah , Nakaya Helder I. , Cunha-Neto Edecio , Gadermaier Gabriele , Kalil Jorge , Coelho Verônica , Santos Keity Souza 
Published: January 2023

IntroductionConsidering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information.MethodsWe used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. ResultsWe found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity.DiscussionThis peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.
Transcriptome and single-cell analysis reveal the contribution of immunosuppressive microenvironment for promoting glioblastoma progression
Authors: Ni Lulu , Sun Ping , Zhang Sujuan , Qian Bin , Chen Xu , Xiong Mengrui , Li Bing 
Published: January 2023

Background and objectivesGBM patients frequently exhibit severe local and systemic immunosuppression, limiting the possible efficacy of immunotherapy strategies. The mechanism through which immunosuppression is established in GBM tumors is the key to successful personalized immunotherapies.MethodsWe divided GBM patients into subtypes according to the expression characteristics of the TME typing-related signature matrix. WGCNA analysis was used to get co-expressed gene modules. The expression activity of hub genes retrieved from co-expressed modules was validated in two single-cell datasets. Then, cell–cell interaction was calculated.ResultsFour subtypes were identified in the TCGA and CGGA RNA-seq datasets simultaneously, one of which was an immunosuppressive subtype rich in immunosuppressive factors with low lymphocyte infiltration and an IDH1 mutation. Three co-expressed gene modules related to the immunosuppressive subtype were identified. These three modules are associated with the inflammatory response, angiogenesis, hypoxia, and carbon metabolism, respectively. The genes of the inflammatory response were mainly related to myeloid cells, especially TAM, angiogenesis was related to blood vessels; hypoxia and glucose metabolism were related to tumors, TAM, and blood vessels. Moreover, there was enhanced interaction between tumor cells and TAM.DiscussionThis research successfully found the immunosuppressive subtype and the major cell types, signal pathways, and molecules involved in the formation of the immunosuppressive subtype and will provide new clues for the improvement of GBM personalized immunotherapy in the future.