bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common Core Genes Play Vital Roles in Gastric Cancer With Different Stages
Authors: Yu Zhiyuan , Liang Chen , Tu Huaiyu , Qiu Shuzhong , Dong Xiaoyu , Zhang Yonghui , Ma Chao , Li Peiyu 
Published: July 2022

Background: Owing to complex molecular mechanisms in gastric cancer (GC) oncogenesis and progression, existing biomarkers and therapeutic targets could not significantly improve diagnosis and prognosis. This study aims to identify the key genes and signaling pathways related to GC oncogenesis and progression using bioinformatics and meta-analysis methods.Methods: Eligible microarray datasets were downloaded and integrated using the meta-analysis method. According to the tumor stage, GC gene chips were classified into three groups. Thereafter, the three groups’ differentially expressed genes (DEGs) were identified by comparing the gene data of the tumor groups with those of matched normal specimens. Enrichment analyses were conducted based on common DEGs among the three groups. Then protein–protein interaction (PPI) networks were constructed to identify relevant hub genes and subnetworks. The effects of significant DEGs and hub genes were verified and explored in other datasets. In addition, the analysis of mutated genes was also conducted using gene data from The Cancer Genome Atlas database.Results: After integration of six microarray datasets, 1,229 common DEGs consisting of 1,065 upregulated and 164 downregulated genes were identified. Alpha-2 collagen type I (COL1A2), tissue inhibitor matrix metalloproteinase 1 (TIMP1), thymus cell antigen 1 (THY1), and biglycan (BGN) were selected as significant DEGs throughout GC development. The low expression of ghrelin (GHRL) is associated with a high lymph node ratio (LNR) and poor survival outcomes. Thereafter, we constructed a PPI network of all identified DEGs and gained 39 subnetworks and the top 20 hub genes. Enrichment analyses were performed for common DEGs, the most related subnetwork, and the top 20 hub genes. We also selected 61 metabolic DEGs to construct PPI networks and acquired the relevant hub genes. Centrosomal protein 55 (CEP55) and POLR1A were identified as hub genes associated with survival outcomes.Conclusion: The DEGs, hub genes, and enrichment analysis for GC with different stages were comprehensively investigated, which contribute to exploring the new biomarkers and therapeutic targets.
Identification and Validation of Cuproptosis-Related Prognostic Signature and Associated Regulatory Axis in Uterine Corpus Endometrial Carcinoma
Authors: Chen Yun 
Published: July 2022

Background: Uterine corpus endometrial carcinoma (UCEC) is a common gynecological malignancy globally with high recurrence and mortality rates. Cuproptosis is a new type of programmed cell death involved in tumor cell proliferation and growth, angiogenesis, and metastasis.Methods: The difference in cuproptosis-related genes (CRGs) between UCEC tissues and normal tissues deposited in The Cancer Genome Atlas database was calculated using the “limma” R package. LASSO Cox regression analysis was conducted to construct a prognostic cuproptosis–related signature. Kaplan–Meier analysis was conducted to compare the survival of UCEC patients. A ceRNA network was constructed to identify the lncRNA–miRNA–mRNA regulatory axis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to verify CRG expression in UCEC.Results: The expression of FDX1, LIAS, DLAT, and CDKN2A were upregulated, whereas the expression of LIPT1, DLD, PDHB, MTF1, and GLS were downregulated in UCEC versus normal tissues. The genetic mutation landscape of CRGs in UCEC was also summarized. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these CRGs were enriched in the tricarboxylic acid (TCA) cycle, glycolysis, and HIF-1 signaling pathway. LASSO Cox regression analysis was performed and identified a cuproptosis-related prognostic signature including these three prognostic biomarkers (CDKN2A, GLS, and LIPT1). UCEC patients with high risk scores had a poor prognosis with an area under the curve of 0.782 and 0.764 on 3- and 5-year receiver operating characteristic curves. Further analysis demonstrated a significant correlation between CDKN2A and pTNM stage, tumor grade, immune cell infiltration, drug sensitivity, tumor mutational burden (TMB) score, and microsatellite instable (MSI) score. The data validation of qRT-PCR further demonstrated the upregulation of CDKN2A and the downregulation of LIPT1 and GLS in UCEC versus normal tissues. The ceRNA network also identified lncRNA XIST/miR-125a-5p/CDKN2A regulatory axis for UCEC.Conclusion: The current study identified a cuproptosis-related prognostic signature including these three prognostic biomarkers (CDKN2A, GLS, and LIPT1) for UCEC. The ceRNA network also identified that lncRNA XIST/miR-125a-5p/CDKN2A regulatory axis may be involved in the progression of UCEC. Further in vivo and in vitro studies should be conducted to verify these results.
Identification and functional analysis of novel SOX11 variants in Chinese patients with Coffin-Siris syndrome 9
Authors: Ding Yu , Chen Jiande , Tang Yijun , Chen Li-Na , Yao Ru-En , Yu Tingting , Yin Yong , Wang Xiumin , Wang Jian , Li Niu 
Published: July 2022

SOX11 is a transcription factor belonging to the sex determining region Y-related high-mobility group box family that plays a vital role in early embryogenesis and neurogenesis. De novo variants in SOX11 have been initially reported to cause a rare neurodevelopmental disorder, mainly referred to Coffin-siris syndrome 9 (CSS9, OMIM# 615866) which is characterized with growth deficiency, intellectual disability (ID), microcephaly, coarse facies, and hypoplastic nails of the fifth fingers and/or toes. A recent large-scale cohort study suggests that SOX11 variation would result in a clinically and molecularly distinct disease from CSS. Here, we describe three unrelated Chinese cases with variable phenotype, mainly involving developmental delay, ID, short statute, microcephaly, facial deformities (i.e., prominent forehead, arched eye brow, flat nasal bridge, broad nose and short philtrum), and cryptorchidism. Whole-exome sequencing (WES) revealed three novel heterozygous variants in the SOX11 gene, including two missense variants of c.337T&gt;C (p.Y113H) and c.425C&gt;G (p.A142G), and one nonsense variant of c.820A&gt;T (p. K142*). Luciferase reporting assay shows that the two missense variants impair the transcriptional activity of the SOX11 target gene GDF5. Additionally, WES uncovered a 4,300 kb deletion involving the region of 1q24.2-q25.1 (hg19,chr1:169,433,149-173,827,682) in patient 1, which also contributes to the condition of the patient. In summary, this is the first report of Chinese cases with de novo variants of SOX11. Our study partially supports the previous observation that the phenotype caused by SOX11 variants somewhat differs from classical CSS.
The lymphocyte-to-monocyte ratio predicts intracranial atherosclerotic stenosis plaque instability
Authors: Wu Xiao-Bing , Huang Li-Xin , Huang Zhong-Run , Lu Li-Ming , Luo Bin , Cai Wang-Qing , Liu An-Min , Wang Sheng-Wen 
Published: July 2022

Background and purposeGadolinium enhancement on high-resolution vessel wall imaging (HR-VWI) is an imaging marker of intracranial atherosclerotic stenosis (ICAS) plaque instability. This study aimed to evaluate the relationships between hematological inflammatory indicators and the enhancement of ICAS plaques and to search for hematological indicators that can predict ICAS plaque instability.MethodsConsecutive adult patients diagnosed with ICAS from April 2018 to December 2021 were recruited retrospectively, and every patient underwent HR-VWI. Plaque enhancement was measured qualitatively and quantitatively. The plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Clinical and laboratory data, including the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII), were recorded. The hematological inflammatory indicators were compared between ICAS patients with and without plaque enhancement and between patients with and without symptomatic plaque. The hematological inflammatory indicators and the CR were compared using linear regression. Furthermore, receiver operating characteristic curve analysis was performed to assess the discriminative abilities of the inflammatory indicators to predict plaque instability.ResultsFifty-nine patients were included. The NLR, SII and LMR were significantly correlated with plaque enhancement. The LMR was independently associated with plaque enhancement, and a linear negative correlation was observed between the LMR and CR (R = 0.716, P &lt; 0.001). The NLR, LMR, plaque enhancement and CR were significantly associated with symptomatic ICAS, and the LMR and plaque enhancement were independent risk factors for symptomatic ICAS. The optimal cutoff value of the admission LMR to distinguish symptomatic plaque from asymptomatic plaque was 4.0 (80.0% sensitivity and 70.6% specificity).ConclusionThe LMR was independently associated with ICAS plaque enhancement and showed a linear negative correlation with CR. The LMR and plaque enhancement were independent risk factors for symptomatic ICAS. An LMR ≤ 4.0 may predict ICAS plaque instability.
Boosting the VZV-Specific Memory B and T Cell Response to Prevent Herpes Zoster After Kidney Transplantation
Authors: Kho Marcia M. L. , Weimar Willem , Malahe S. Reshwan K. , Zuijderwijk Joke M. , de Kuiper Ronella , Boer-Verschragen Marieken J. , Eijk Annemiek A. van der , Hesselink Dennis A. , Reinders Marlies E. J. , van Besouw Nicole M. 
Published: July 2022

BackgroundSolid organ transplant recipients are at high risk to develop (complicated) herpes zoster (HZ). Booster vaccination could prevent HZ. However, end-stage renal disease (ESRD) patients show poor immunological responses to vaccinations. We studied the effect of a live attenuated VZV booster vaccine on VZV-specific B and T cell memory responses in ESRD patients and healthy controls. NL28557.000.09, www.toetsingonline.nlMethodsVZV-seropositive patients, aged ≥50 years, awaiting kidney transplantation, were vaccinated with Zostavax®. Gender and age-matched VZV-seropositive potential living kidney donors were included as controls. VZV-specific IgG titers were measured before, at 1, 3 and 12 months post-vaccination. VZV-specific B and T cell responses before, at 3 months and 1 year after vaccination were analysed by flow-cytometry and Elispot, respectively. Occurrence of HZ was assessed at 5 years post-vaccination.Results26 patients and 27 donors were included. Median VZV-specific IgG titers were significantly higher at all time-points post-vaccination in patients (mo 1: 3104 IU/ml [1967-3825], p&lt;0.0001; mo 3: 2659 [1615-3156], p=0.0002; mo 12: 1988 [1104-2989], p=0.01 vs. pre: 1397 [613-2248]) and in donors (mo 1: 2981 [2126-3827], p&lt;0.0001; mo 3: 2442 [2014-3311], p&lt;0.0001; mo 12: 1788 [1368-2460], p=0.0005 vs. pre: 1034 [901-1744]. The patients’ IgG titers were comparable to the donors’ at all time-points. The ratio VZV-specific B cells of total IgG producing memory B cells had increased 3 months post-vaccination in patients (0.85 [0.65-1.34] vs. pre: 0.56 [0.35-0.81], p=0.003) and donors (0.85 [0.63-1.06] vs. pre: 0.53 [0.36-0.79], p&lt;0.0001) and remained stable thereafter in donors. One year post-vaccination, the percentage of CD4+ central memory cells had increased in both patients (0.29 [0.08-0.38] vs. 0.12 [0.05-0.29], p=0.005) and donors (0.12 [0.03-0.37] vs. 0.09 [0.01-0.20], p=0.002) and CD4+ effector memory cells had increased in donors (0.07 [0.02-0.14] vs. 0.04 [0.01-0.12], p=0.007). Only 1 patient experienced HZ, which was non-complicated.ConclusionVZV booster vaccination increases VZV-specific IgG titers and percentage VZV-specific memory T-cells for at least 1 year both in ESRD patients and healthy controls. VZV-specific memory B cells significantly increased in patients up to 3 months after vaccination. Prophylactic VZV booster vaccination prior to transplantation could reduce HZ incidence and severity after transplantation.
The intellectual base and research fronts of IL-37: A bibliometric review of the literature from WoSCC
Authors: Qin Ya-fei , Ren Shao-hua , Shao Bo , Qin Hong , Wang Hong-da , Li Guang-ming , Zhu Yang-lin , Sun Cheng-lu , Li Chuan , Zhang Jing-yi , Wang Hao 
Published: July 2022

BackgroundIL-37 is a recently identified cytokine with potent immunosuppressive functions. The research fronts of IL-37 are worth investigating, and there is no bibliometric analysis in this field. The purpose of this study is to construct the intellectual base and predict research hotspots of IL-37 research both quantitatively and qualitatively according to bibliometric analysis.MethodsThe articles were downloaded from the Web of Science Core Collection (WoSCC) database from the inception of the database to 1 April 2022. CiteSpace 5.8.R3 (64-bit, Drexel University, Philadelphia, PA, USA) and Online Analysis Platform of Literature Metrology (https://bibliometric.com/) were used to perform bibliometric and knowledge-map analyses.ResultsA total of 534 papers were included in 200 academic journals by 2,783 authors in 279 institutions from 50 countries/regions. The journal Cytokine published the most papers on IL-37, while Nature Immunology was the most co-cited journal. The publications belonged mainly to two categories of Immunology and Cell Biology. USA and China were the most productive countries. Meanwhile, the University of Colorado Denver in USA produced the highest number of publications followed by Radboud University Nijmegen in the Netherlands and Monash University in Australia. Charles A. Dinarello published the most papers, while Marcel F. Nold had the most co-citations. Top 10 co-citations on reviews, mechanisms, and diseases were regarded as the knowledge base. The keyword co-occurrence and co-citations of references revealed that the mechanisms and immune-related disorders were the main aspects of IL-37 research. Notably, the involvement of IL-37 in various disorders and the additional immunomodulatory mechanisms were two emerging hotspots in IL-37 research.ConclusionsThe research on IL-37 was thoroughly reviewed using bibliometrics and knowledge-map analyses. The present study is a benefit for academics to master the dynamic evolution of IL-37 and point out the direction for future research.
Microstructure and Mechanical Properties of High-Carbon-Containing Fe-Ni-Mn-Al-Cr High-Entropy Alloy: Effect of Thermomechanical Treatment
Authors: Mohanty S. , Kothari A. , Raghavan R. , Sahu V. K. , Gurao N. P. , Sahu K. K. , Dhindaw B. K. , Zeng L. , Xia M. , Gollapudi S. 
Published: July 2022

The effect of heat treatment on the mechanical properties of two high-carbon-containing (1.5 and 3 at%) single-phase face-centered cubic (fcc) Fe40.4Ni11.3Mn34.8Al7.5Cr6 high-entropy alloys is reported in this study. In the cold-rolled (CR) condition, the 1.5 and 3 at% C-containing alloys, referred to as CR1 and CR2, respectively, demonstrated yield strength values of 1,423 and 1,197 MPa, respectively. The corresponding values of elongation to failure was noted to be 4.05 and 4.46%, respectively. Upon heat treatment at 1,050°C, the CR1 and CR2 samples, referred to as HT1 and HT2 in the heat-treated (HT) condition, demonstrated yield strength values of 358 and 327 MPa, respectively. The elongation to failure of HT1 and HT2 was found to be 37.2 and 26.4%, respectively. The change in mechanical properties brought about by heat treatment was understood by studying the phase composition, microstructure, and crystallographic texture of the material in the CR and HT conditions. Despite the high-temperature heat treatment, the Fe40.4Ni11.3Mn34.8Al7.5Cr6 alloy retained a single-phase structure, indicating good phase stability. However, heat treatment caused a change in the grain structure. The CR materials exhibited an elongated grain structure, whereas the HT materials had an equiaxed microstructure. The CR and HT samples were found to exhibit a weak crystallographic texture although heat treatment had caused the {111} poles to orient themselves parallel to the rolling plane, whereas the CR material had a distribution of {200} poles at 45° to the rolling plane.
The numerical analysis of the acoustic streaming effect of a cavity acoustic black hole
Authors: Huang Meilian , Liang Xiao , Su Liang , He Xingyun , Li Danni , Chu Jiaming , Wang Shengsheng , Liang Haofeng , Zhang Yongyan 
Published: July 2022

In this study, we use numerical methods to study the acoustic streaming effect of the acoustic black hole (ABH). Firstly, we build an ABH model to study the acoustic streaming effect. By deriving the waves equations and solving the Navier–Stokes equations, we obtain the flow field, sound field, and temperature field under the acoustic excitation. Secondly, the simulation result reveals the mechanism of acoustic streaming effects on the sound transmission characteristics of cavity ABH. The numerical results show that the abrupt decrease in the sound pressure is caused by the great changes in the velocity gradient caused by the catastrophe of cross section. The energy of the sound waves can also be dissipated by the thermal viscous layer at low frequencies. Finally, based on the acoustic streaming effects of the acoustic medium in the ABH, we propose feasible methods to enhance the sound insulation. Increasing the cross section of the cavity in ABH can get a better sound insulation effect at high frequencies, and decreasing the cross section can improve Sound Transmission Loss (STL). Through optimization, STL can reach more than 25 dB at low frequencies.
The regulatory challenges of innovative customized combination products
Authors: Reis Mariana E. , Bettencourt Ana , Ribeiro Helena M. 
Published: July 2022

Background/aimsCombination products are therapeutic and/or diagnostic products that can combine drugs and medical devices and which increasing complexity has raised new regulatory framework challenges. To reach the market, a combination product must be classified based on the principal mode of action (PMOA). However, research and technological progress has been leading to the development of novel combination products with no clearly defined PMOA, emphasizing the lack of a systematization process, thus challenging the correct classification of these products. To illustrate the regulatory challenge, two case studies are discussed: innovative combination products with PMOA that can change due to an external stimulus, specifically custom-made 3D-printed scaffolds with incorporated medicinal substances.MethodsData was collected through computational search engines, regulatory agencies and equally relevant associations. The analysis of the data resulted on this state-of-the-art review, a description of the decision-making process by the regulatory authorities, and case studies analysis that culminated in the proposal of a decision-tree scheme.FindingsCurrent regulations do not fully address complex combination products namely personalized 3D-printed scaffolds. Two merged regulatory approaches are suggested along with the schematization of the rational assisted by a decision-tree tool.ConclusionCombination products have become increasingly sophisticated, which has furthered the need to develop multidisciplinary collaborations within the health sector to adapt to these innovative healthcare solutions as well as with regulators to overcome the challenges posed for their classification.
New integrated weaning indices from mechanical ventilation: A derivation-validation observational multicenter study
Authors: Vahedian-Azimi Amir , Gohari-Moghadam Keivan , Rahimi-Bashar Farshid , Samim Abbas , Khoshfetrat Masoum , Mohammadi Seyyede Momeneh , de Souza Leonardo Cordeiro , Mahmoodpoor Ata 
Published: July 2022

BackgroundTo develop ten new integrated weaning indices that can predict the weaning outcome better than the traditional indices.MethodsThis retrospective-prospective derivation-validation observational multicenter clinical trial (Clinical Trial.Gov, NCT 01779297), was conducted on 1,175 adult patients admitted at 9 academic affiliated intensive care units (ICUs; 4 surgical and 5 medical), from Jan 2013 to Dec 2018. All patients, intubated and mechanically ventilated for at least 24 h and ready for weaning were enrolled. The study had two phases: at first, the threshold values of each index that best discriminate between a successful and an unsuccessful weaning outcome was determined among 208 patients in the derivation group. In the second phase, the predictive performance of these values was prospectively tested in 967 patients in the validation group. In the prospective-validation set we used Bayes’ theorem to assess the probability of each test in predicting weaning.ResultsIn the prospective validation group, sensitivity, specificity, diagnostic accuracy, positive and negative predictive values, and finally area under the receiver operator characteristic curves and standard errors for each index (ten formulae) were calculated. Statistical values of ten formulae for aforesaid variables were higher than 87% (0.87–0.99).ConclusionThe new indices can be used for hospitalized patients in intensive care settings for accurate prediction of the weaning outcome.
Burden of tuberculosis and its association with socio-economic development status in 204 countries and territories, 1990–2019
Authors: Xue Yi , Zhou Jie , Wang Peng , Lan Jun-hong , Lian Wen-qin , Fan Yue-Ying , Xu Bei-Ni , Yin Jia-Peng , Feng Zi-hao , Zhou Jian , Jia Chi-Yu 
Published: July 2022

BackgroundTuberculosis (TB) always runs in the forefront of the global burden when it comes to infectious diseases. Tuberculosis, which can lead to impairment of quality of life, financial hardship, discrimination, marginalization, and social barriers, is a major public health problem. The assessment of TB burden and trend can provide crucial information for policy decision and planning, and help countries in the world to achieve the goal of sustainable development of ending the epidemic of TB in 2030.MethodsAll data are from the Global Burden of Disease 2019 (GBD 2019) database, which analyzed the burden trend of age-standardized incidence, DALYs, and deaths rate in TB and HIV/AIDS-infected TB over the past 30 years. Also, GBD 2019 not only analyzed the burden distribution of TB in 204 countries and main regions of the world but also analyzed the relationship between the burden of global TB and the socio–demographic Index (SDI).ResultsThe age-standardized incidence, age-standardized disability-adjusted life years (DALYs), and age-standardized deaths rate for HIV-negative TB were 10,671.45 (9,395.60–12,194.10), 59,042.45 (53,684.78–64,641.53), and 1,463.62 (1,339.24–1,602.71) (95% CI, per 100,000 person-years) in 2019, respectively. Age-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of HIV/AIDS-XDR-TB (95% CI, per 1,000 person-years) were 2.10 (1.51–2.90), 64.23 (28.64–117.74), and 1.01 (0.42–1.86), respectively. We found that TB is inversely proportional to SDI, the age-standardized incidence, DALYs, and deaths rate low burden countries were in high SDI areas, while high burden countries were in low SDI areas. The global TB showed a slow decline trend, but the age-standardized incidence of HIV-positive TB was increasing, and mainly distributed in sub-Saharan Africa.ConclusionAge-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of TB is related to SDI, and the burden of low SDI countries is lighter than that of high SDI countries. Without effective measures, it will be difficult for countries around the world to achieve the goal of ending the TB epidemic by 2030. Effective control of the spread of TB requires concerted efforts from all countries in the world, especially in the countries with low SDI, which need to improve the diagnosis and preventive measures of TB and improve the control of HIV/AIDS-TB.