bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of Different Hypoxia Patterns and Construction of a Hypoxia-Related Gene Prognostic Index in Colorectal Cancer
Authors: Bai Shuheng , Chen Ling , Yan Yanli , Li Rong , Zhou Yun , Wang Xuan , Kang Haojing , Feng Zhaode , Li Guangzu , Zhou Shuling , Drokow Emmanuel Kwateng , Ren Juan 
Published: June 2022

IntroductionImmune checkpoint inhibitor (ICI) therapy has been proven to be a highly efficacious treatment for colorectal adenocarcinoma (COAD). However, it is still unclear how to identify those who might benefit the most from ICI therapy. Hypoxia facilitates the progression of the tumor from different aspects, including proliferation, metabolism, angiogenesis, and migration, and improves resistance to ICI. Therefore, it is essential to conduct a comprehensive understanding of the influences of hypoxia in COAD and identify a biomarker for predicting the benefit of ICI.MethodsAn unsupervised consensus clustering algorithm was used to identify distinct hypoxia-related patterns for COAD patients from TCGA and the GEO cohorts. The ssGSEA algorithm was then used to explore the different biological processes, KEGG pathways, and immune characteristics among distinct hypoxia-related clusters. Some hypoxia-related hub genes were then selected by weighted gene coexpression network analysis (WGCNA). Subsequently, univariate Cox regression analysis, multivariate Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) regression were utilized to construct a hypoxia-related gene prognostic index (HRGPI). Finally, validation was also conducted for HRGPI in prognostic value, distinguishing hypoxia-related characteristics and benefits of ICI.ResultsWe identified four hypoxia-related clusters and found that different hypoxia response patterns induced different prognoses significantly. Again, we found different hypoxia response patterns presented distinct characteristics of biological processes, signaling pathways, and immune features. Severe hypoxia conditions promoted activation of some cancer-related signaling pathways, including Wnt, Notch, ECM-related pathways, and remodeled the tumor microenvironment of COAD, tending to present as an immune-excluded phenotype. Subsequently, we selected nine genes (ANO1, HOXC6, SLC2A4, VIP, CD1A, STC2, OLFM2, ATP6V1B1, HMCN2) to construct our HRGPI, which has shown an excellent prognostic value. Finally, we found that HRGPI has an advantage in distinguishing immune and molecular characteristics of hypoxia response patterns, and it could also be an excellent predictive indicator for clinical response to ICI therapy.ConclusionDifferent hypoxia response patterns activate different signaling pathways, presenting distinct biological processes and immune features. HRGPI is an independent prognostic factor for COAD patients, and it could also be used as an excellent predictive indicator for clinical response to ICI therapy.
Low Memory T Cells Blood Counts and High Naïve Regulatory T Cells Percentage at Relapsing Remitting Multiple Sclerosis Diagnosis
Authors: Canto-Gomes João , Silva Carolina S. , Rb-Silva Rita , Boleixa Daniela , da Silva Ana Martins , Cheynier Rémi , Costa Patrício , González-Suárez Inés , Correia-Neves Margarida , Cerqueira João J. , Nobrega Claudia 
Published: June 2022

ObjectiveThe aim of this study is to assess the peripheral immune system of newly diagnosed patients with relapsing remitting multiple sclerosis (RRMS) and compare it to healthy controls (HC).MethodsThis cross-sectional study involves 30 treatment-naïve newly diagnosed patients with RRMS and 33 sex- and age-matched HC. Peripheral blood mononuclear cells were analyzed regarding: i) thymic function surrogates [T cell receptor excision circles (TRECs) and recent thymic emigrants (RTEs)]; ii) naïve and memory CD4+ and CD8+ T cells subsets; iii) T helper (Th) phenotype and chemokine receptors expression on CD8+ T cells subsets; iv) regulatory T cell (Tregs) phenotype; and exclude expression of activating/inhibitory receptors by natural killer (NK) and NKT cells. Analyses were controlled for age, sex, and human cytomegalovirus (HCMV) IgG seroprevalence.ResultsNewly diagnosed patients with RRMS and HC have equivalent thymic function as determined by similar numbers of RTEs and levels of sjTRECs, DJβTRECs, and sj/DJβTREC ratio. In the CD8+ T cells compartment, patients with RRMS have a higher naive to memory ratio and lower memory cell counts in blood, specifically of effector memory and TemRA CD8+ T cells. Interestingly, higher numbers and percentages of central memory CD8+ T cells are associated with increasing time from the relapse. Among CD4+ T cells, lower blood counts of effector memory cells are found in patients upon controlling for sex, age, and anti-HCMV IgG seroprevalence. Higher numbers of CD4+ T cells (both naïve and memory) and of Th2 cells are associated with increasing time from the relapse; lower numbers of Th17 cells are associated with higher MS severity scores (MSSS). Patients with RRMS have a higher percentage of naïve Tregs compared with HC, and lower percentages of these cells are associated with higher MSSS. Percentages of immature CD56bright NK cells expressing the inhibitory receptor KLRG1 and of mature CD56dimCD57+ NK cells expressing NKp30 are higher in patients. No major alterations are observed on NKT cells.ConclusionCharacterization of the peripheral immune system of treatment-naïve newly diagnosed patients with RRMS unveiled immune features present at clinical onset including lower memory T cells blood counts, particularly among CD8+ T cells, higher percentage of naïve Tregs and altered percentages of NK cells subsets expressing inhibitory or activating receptors. These findings might set the basis to better understand disease pathogenesis.
Vertical Profiles of 226Ra and 228Ra Activity Concentrations in the Western Subarctic Gyre of the Pacific Ocean
Authors: Tazoe Hirofumi , Obata Hajime , Hara Takuya , Inoue Mutsuo , Tanaka Takahiro , Nishioka Jun 
Published: June 2022

The vertical activity concentration distributions of the radium isotopes, 226Ra and 228Ra, which are useful as radiotracers, were obtained for the first time in the western Subarctic Pacific Gyre (WSAG). It was possible to detect short-lived 228Ra present from the surface to 400 m depth by analyzing large seawater samples. Low 228Ra and high 226Ra activity concentrations in the surface layer in the WSAG were strongly influenced by upwelled deeper water with nutrients. The activity concentration distribution of 226Ra especially was in good agreement with the silicate concentration distribution, which was consistent with previous reported findings. These distributions were uniform from the surface to 100 m of the dichothermal layer due to vertical mixing in winter. 228Ra activity concentration decreased with water depth below the pycnocline and reached the undetectable level at 600 m which was within the oxygen minimum layer. Estimations of vertical fluxes of 228Ra and nitrate according to 228Ra decay indicated that the vertical transport by eddy diffusion was a minor process for the 228Ra and nitrate fluxes, and lateral transport mainly affected 228Ra in the intermediate warm water, that is, the mesothermal layer below the main pycnocline. Vertical mixing or submarine underground water and lateral transport to the WSAG could yield this 228Ra in the intermediate depth.
Defining an Optimal Sample Size for Corneal Epithelial Immune Cell Analysis Using in vivo Confocal Microscopy Images
Authors: Zhang Xin Yuan , Wu Mengliang , Chinnery Holly R. , Downie Laura E. 
Published: June 2022

PurposeIn vivo confocal microscopy (IVCM) images are frequently used to quantify corneal epithelial immune cell (IC) density in clinical studies. There is currently limited evidence to inform the selection of a representative image sample size to yield a reliable IC density estimate, and arbitrary numbers of images are often used. The primary aim of this study was to determine the number of randomly selected, unique IVCM images required to achieve an acceptable level of accuracy when quantifying epithelial IC density, in both the central and peripheral cornea. The secondary aim was to evaluate the consistency and precision of an image selection approach where corneal epithelial IC density was quantified from “three representative images” selected independently by three experienced observers.MethodsAll combinations of two to 15 non-overlapping IVCM images were used for deriving IC density estimates, for both the central and peripheral cornea, in 20 healthy participants; the density value from averaging quantifications in the 16 images was defined as the “true mean”. IC density estimates were compared with the true mean in each corneal region using a mean ratio. Intraclass correlation coefficients (ICCs) were used to evaluate the consistency of the mean ratios of IC density estimates derived from the method involving the manual selection of “three representative images” by the observers. The precision of the IC density estimates was compared to a scenario involving three randomly selected images.ResultsA total of 12 randomly selected, non-overlapping IVCM images were found to be required to produce a corneal epithelial IC density estimate that was within 30% of the true mean, 95% of the time, for the central cornea; seven such images produced an equivalent level of precision in the peripheral cornea. Mean ratios of corneal IC density estimates derived from “three representative images” methods had poor consistency between observers (ICC estimates &lt;0.5) and similar levels of precision when compared with using three randomly selected images (p &gt; 0.05 for all comparisons), in both the central and peripheral cornea.ConclusionsData presented in this study can inform image selection methods, and the sample size required for a preferred level of accuracy, when quantifying IC densities in the central and peripheral corneal epithelium using IVCM images.
A Bibliometric Analysis of 100 Most-Cited Articles on Corneal Cross-Linking
Authors: Yang Kaili , Xu Liyan , Wang Shaopei , Zhu Meng , Fan Qi , Gu Yuwei , Wang Yawen , Wang Qing , Zhao Dongqing , Pang Chenjiu , Ren Shengwei 
Published: June 2022

BackgroundHighly cited papers are expected to have high-quality data that significantly contribute to the body of knowledge. The study aimed to evaluate the characters of the 100 most-cited articles on corneal cross-linking (CXL) through a bibliometric analysis.Materials and MethodsThe Web of Science database was searched to identify papers published from 1950 to 2020. A bibliometric analysis of the top 100-cited articles was conducted in the current study. The citation differences between basic research, clinical research, and reviews were compared by Kruskal–Wallis test. The association between citations and publication year was evaluated by Spearman correlation analysis. The VOSviewer software was used to create networks of co-authorship and keywords map.ResultsThe median values of the number of citations, citations/year since publication, and citations since 2013 were 101, 9.5, and 11.92, respectively. A total of 61% of articles were clinical research. The citations since 2013 of clinical research were lower than basic research and the reviews (all p &lt; 0.001). The publication year was positively correlated with the number of publications (r = 0.665, p = 0.013), and the total number of citations decreased for basic research (r = –0.447, p = 0.017), and clinical research (r = –0.433, p &lt; 0.001). The J REFRACT SURG publishes the highest number of articles. The corresponding authors were predominantly from the Italy (N = 17), Germany (N = 16), and United States (N = 15). Spoerl Eberhard has the highest number of citations and total link strength with 15 articles. Extensive collaboration existed among the main core nodes containing “cross-linking (N = 45),” “riboflavin (N = 44),” and “ultraviolet A (UVA) (N = 42).”ConclusionThe present study focused on the comprehensive analysis of the top 100-cited articles on the CXL research, providing insight into research developments over the past decades.
Integration of scRNA-Seq and TCGA RNA-Seq to Analyze the Heterogeneity of HPV+ and HPV- Cervical Cancer Immune Cells and Establish Molecular Risk Models
Authors: Wei Erdong , Reisinger Amin , Li Jiahua , French Lars E. , Clanner-Engelshofen Benjamin , Reinholz Markus 
Published: June 2022

BackgroundNumerous studies support that Human papillomavirus (HPV) can cause cervical cancer. However, few studies have surveyed the heterogeneity of HPV infected or uninfected (HPV+ and HPV-) cervical cancer (CESC) patients. Integration of scRNA-seq and TCGA data to analyze the heterogeneity of HPV+ and HPV- cervical cancer patients on a single-cell level could improve understanding of the cellular mechanisms during HPV-induced cervical cancer.MethodsCESC scRNA-seq data obtained from the Gene Expression Omnibus (GEO) database and the Seurat, Monocle3 package were used for scRNA-seq data analysis. The ESTIMATE package was used for single-sample gene immune score, CIBERSORT package was used to identify immune scores of cells, and the “WGCNA” package for the weighted correlation network analysis. Univariate Cox and LASSO regression were performed to establish survival and relapse signatures. KEGG and GO analyses were performed for the signature gene. Gene Expression Profiling Interactive Analysis was used for Pan-cancer analysis.ResultsIn the HPV+ CESC group, CD8+ T cells and B cells were down-regulated, whereas T reg cells, CD4+ T cells, and epithelial cells were up-regulated according to scRNA-seq data. Survival analysis of TCGA-CESC revealed that increased expression of naive B cells or CD8+ T cells favors the survival probability of CESC patients. WGCNA, univariate Cox, and LASSO Cox regression established a 9-genes survival signature and a 7-gene relapse model. Pan-cancer analysis identified IKZF3, FOXP3, and JAK3 had a similar distribution and effects in HPV-associated HNSC.ConclusionAnalysis of scRNA-seq and bulk RNA-seq of HPV+ and HPV- CESC samples revealed heterogeneity from transcriptional state to immune infiltration. Survival and relapse models were adjusted according to the heterogeneity of HPV+ and HPV- CESC immune cells to assess the prognostic risk accurately. Hub genes represent similar protection in HPV- associated HNSC while showing irrelevant to other potential HPV-related cancers.
Meta-Analysis of Risk Factors and Incidence of Interstitial Pneumonia With CHOP-Like Regimens for Non-Hodgkin Lymphoma
Authors: Yang Jing , Chai Limin , Jia Junting , Su Liping , Hao Zhiying 
Published: June 2022

ObjectivesInterstitial pneumonitis (IP), a potentially fatal complication of non-Hodgkin Lymphoma (NHL) patients received CHOP (cyclophosphamide and doxorubicin and vincristine and prednisone)-like chemotherapy, negatively affected patients’ clinical outcome and quality of life. We aimed to explore patient-related, disease-related and drug-related risk factors associated with IP and gain a better understanding of the incidence in NHL patients.MethodsDatabases, including PubMed, Ovid, China National Knowledge Internet (CNKI), and Wanfang Database from inception to January 20, 2022, were searched to identify studies evaluating the risk factors and incidence of IP. The included studies were assessed by Newcastle-Ottawa Quality Scale and above 7 points was considered high quality. The statistical analysis of risk factors was assessed by RevMan software (version 5.3) and incidence of IP was calculated by R software (version 4.1.2). Fixed-or random-effects models were applied to estimated the relative risks (RRs) and 95% confidence interval (Cl).ResultsA total of 12 studies comprised of 3423 NHL patients were included in the analysis. Among the 3 available patient-related risk factors, 6 disease-related risk factors and 3 drug-related risk factors, it was found that only drug-related risk factors were significantly associated with IP development: pegylated liposomes doxorubicin (PLD) replacement (RR = 3.25, 95% CI = 1.69-6.27, I2 =64%), rituximab (RTX) addition (RR = 4.24, 95% CI = 2.58-6.96, I2 =0) and granulocyte colony stimulating factor (G-CSF) administration (RR = 5.80, 95% CI = 3.05-11.05, I2 =0). The pooled incidence of CHOP, R-CHOP, and R-CDOP regimen was 1.0% (95% CI 0.00-0.01, I2 = 8%), 7.0% (95% CI 0.05-0.09, I2 = 64%) and 22.0% (95% CI 0.13-0.32, I2 = 87%) respectively.ConclusionPLD replacement, RTX addition and G-CSF administration were significant risk factors of IP for NHL patients received the CHOP-like chemotherapy. Clinicians should focus on these patients to detect and treat the IP development timely, which might bring benefit in patients’ survival.Systematic Review RegistrationPROSPERO, identifier CRD42022309884.
Neuronal Sprouting and Reorganization in Bone Tissue Infiltrated by Human Breast Cancer Cells
Authors: Hansen Rie B. , Sayilekshmy Manasi , Sørensen Michala S. , Jørgensen Astrid H. , Kanneworff Ida B. , Bengtsson Emma K. E. , Grum-Schwensen Tomas A. , Petersen Michael M. , Ejersted Charlotte , Andersen Thomas L. , Andreasen Christina M. , Heegaard Anne-Marie 
Published: June 2022

BackgroundPain is a common complication for patients with metastatic bone disease. Animal models suggest that the pain, in part, is driven by pathological sprouting and reorganization of the nerve fibers innervating the bone. Here, we investigate how these findings translate to humans.MethodsBone biopsies were collected from healthy volunteers (n = 7) and patients with breast cancer and metastatic bone disease (permissions H-15000679, S-20180057 and S-20110112). Cancer-infiltrated biopsies were from patients without recent anticancer treatment (n = 10), patients with recent anticancer treatment (n = 10), and patients with joint replacement surgery (n = 9). Adjacent bone sections were stained for (1) protein gene product 9.5 and CD34, and (2) cytokeratin 7 and 19. Histomorphometry was used to estimate the area of bone marrow and tumor burden. Nerve profiles were counted, and the nerve profile density calculated. The location of each nerve profile within 25 μm of a vascular structure and/or cancer cells was determined.ResultsCancer-infiltrated bone tissue demonstrated a significantly higher nerve profile density compared to healthy bone tissue. The percentage of nerve profiles found close to vascular structures was significantly lower in cancer-infiltrated bone tissue. No difference was found in the percentage of nerve profiles located close to cancer between the subgroups of cancer-infiltrated bone tissue. Interestingly, no correlation was found between nerve profile density and tumor burden.ConclusionsTogether, the increased nerve profile density and the decreased association of nerve profiles to vasculature strongly suggests that neuronal sprouting and reorganization occurs in human cancer-infiltrated bone tissue.
Formononetin Ameliorates Renal Dysfunction, Oxidative Stress, Inflammation, and Apoptosis and Upregulates Nrf2/HO-1 Signaling in a Rat Model of Gentamicin-Induced Nephrotoxicity
Authors: Althunibat Osama Y. , Abukhalil Mohammad H. , Aladaileh Saleem H. , Qaralleh Haitham , Al-Amarat Wesam , Alfwuaires Manal A. , Algefare Abdulmohsen I. , Namazi Nader Ibrahim , Melebary Sahar J. , Babalghith Ahmad O. , Conte-Junior Carlos Adam 
Published: June 2022

Gentamicin (GEN) is a bactericidal aminoglycoside known to cause nephrotoxicity. Formononetin (FN) is a potent flavonoid that exhibits numerous promising pharmacological activities. In this study, we have assessed the nephroprotective efficacy of FN against GEN-induced renal injury in rats. Rats were orally administered with FN (60 mg/kg/day, for 2 weeks) and were co-treated with intraperitoneal (i.p.) injection of GEN (100 mg/kg/day) during the days 8–14. GEN-treated rats demonstrated increased urea and creatinine levels in serum associated with marked histopathological changes in the kidney. Malondialdehyde (MDA) and protein carbonyl contents were elevated, whereas glutathione concentration and catalase and superoxide dismutase activities were lowered in GEN-administered rats. The FN largely prevented tissue damage, attenuated renal function, reduced MDA and protein carbonyl, and enhanced antioxidant capacity in the kidney of GEN-administrated animals. The kidney of GEN-treated rats demonstrated elevated Bax and caspase-3 protein expression, accompanied by lowered Bcl-2 protein expression, an effect that FN attenuated. Moreover, FN treatment caused upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in renal tissue of GEN-intoxicated animals. Collectively, FN protects against GEN-caused renal damage via exhibiting antioxidant, anti-inflammatory, and antiapoptotic activities and augmenting Nrf2 signaling, suggesting FN as a promising agent for preventing drug-induced organ damage.
Oscillatoria sp. as a Potent Anti-phytopathogenic Agent and Plant Immune Stimulator Against Root-Knot Nematode of Soybean cv. Giza 111
Authors: Ghareeb Rehab Y. , Abdelsalam Nader R. , El Maghraby Dahlia M. , Ghozlan Mahmoud H. , EL-Argawy Eman , Abou-Shanab Reda A. I. 
Published: June 2022

BackgroundPlant-parasitic nematodes are one of the major constraints to soybean production around the world. Plant-parasitic nematodes cause an estimated $78 billion in annual crop losses worldwide, with a 10–15% crop yield loss on average. Consequently, finding and applying sustainable methods to control diseases associated with soybean is currently in serious need.MethodsIn this study, we isolated, purified, characterized, and identified a novel cyanobacterial strainOscillatoriasp. (blue-green alga). Based on its microscopic examination and 16S rRNA gene sequence, the aqueous and methanolic extracts ofOscillatoriawere used to test their nematicidal activity againstMeloidogyne incognitahatchability of eggs after 72 h of exposure time and juvenile mortality percentagein vitroafter 24, 48, and 72 h of exposure time and reduction percentage of galls, eggmass, female number/root, and juveniles/250 soil. Also, the efficacy of the extract on improving the plant growth parameter and chlorophyll content under greenhouse conditions on soybean plant cv. Giza 111 was tested. Finally, the expression of PR-1, PR-2, PR-5, and PR15 (encoding enzymes) genes contributing to plant defense in the case ofM. incognitainvasion was studied and treated withOscillatoriaextract.ResultsThe aqueous and methanolic extracts ofOscillatoriasp. had nematicidal activity againstM. incognita. The percentage of mortality and egg hatching ofM. incognitawere significantly increased with the increase of time exposure toOscillatoriaextract 96.7, 97, and 98 larvae mortality % with S concentration after 24, 48, and 72 h of exposure time. The aqueous extract significantly increased the percentage of Root-Knot nematodes (RKN) of egg hatching, compared with Oxamyl and methanol extract at 96.7 and 97% after 72 h and 1 week, respectively. With the same concentration in the laboratory experiment. Furthermore, water extracts significantly reduced the number of galls in soybean root, egg masses, and female/root by 84.1, 87.5, and 92.2%, respectively, as well as the percentage of J2s/250 g soil by 93.7%. Root, shoot lengths, dry weight, number of pods/plant, and chlorophyll content of soybean treated withOscillatoriawater extract were significantly higher than the control increasing by 70.3, 94.1, 95.5, and 2.02%, respectively. The plant defense system's gene expression was tracked using four important pathogenesis-related genes, PR-1, PR-2, PR-5, and PR15, which encode enzymes involved in plant defense.ConclusionsOscillatoriaextract is a potential nematicide against root-knot nematode invasion in soybean.