bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclophilin A causes severe fever with thrombocytopenia syndrome virus-induced cytokine storm by regulating mitogen-activated protein kinase pathway
Authors: Huang Huaying , Jin Ke , Ouyang Ke , Jiang Zhengyi , Yang Zhan , Hu Nannan , Dai Yan , Zhang Yaqin , Zhang Qian , Han Ying , Zhao Jie , Lin Hong , Wang Chunhui , Wang Chunyan , Sun Xuewei , Lu Dafeng , Zhu Jin , Li Jun 
Published: December 2022

IntroductionSevere fever with thrombocytopenia syndrome (SFTS) has become a global threat to public health since its first report in China in 2009. However, the pathogenesis of SFTS virus (SFTSV) in humans remains unclear. Also, there are no effective therapeutics for SFTS. Cyclophilin A (CyPA) regulates protein folding and trafficking involved in various viral infectious diseases, but its role in SFTSV infection has not been elucidated.MethodsWe detected plasma CyPA levels in 29 healthy subjects and 30 SFTS patients by ELISA. In THP-1 cells and normal human peripheral blood mononuclear cells (PBMCs), SFTSV-induced extracellular CyPA (eCyPA) was also detected by ELISA. In THP-1, the effects of CyPA on Mitogen-activated protein kinase (MAPK) pathway and NF-κB were determined by Western blot. We validated the interaction between CypA and CD147 by human recombinant CyPA (hrCyPA) and the CD147 inhibitor. Effects of CyPA inhibitor Cyclosporine A (CsA) on cytokines and SFTSV replication in THP-1 cells was also detected. 8-week-old Interferon-α/β Receptor (IFNAR) knockout (IFNAR-/-) C57BL/6 mice were divided into mock group, 106TCID50 SFTSV (Untreated) group and 106TCID50 SFTSV+CsA (CsA-treated) group. The changes of body weight, animal behavior and survival time of each group were recorded. Blood samples were collected from tail vein regularly. After death, the liver, spleen, lung, kidney and brain were collected for pathological HE staining and SFTSV-NP immunohistochemical staining.ResultsCompared to healthy subjects and SFTS patients in the febrile phase of the disease, plasma CyPA levels in SFTS patients at the multi-organ dysfunction (MOD) phase showed significantly elevated (P &lt; 0.01). Extracellular CyPA activates the MAPK pathway by binding to CD147 in THP-1 infected with SFTSV. CsA inhibits the pro-inflammatory and promoting replication effects of CyPA after SFTSV infection in vitro. In vivo, CsA can prolong the survival time and delay the weight loss of SFTSV mice. CsA reduces multi-organ dysfunction in IFNAR−/− mice infected with SFTSV.DiscussionOur results indicate that CyPA is associated with SFTSV-induced cytokine storm, which can be a potential target for SFTS therapy.
Individual and combined contamination of oxytetracycline and cadmium inhibited nitrification by inhibiting ammonia oxidizers
Authors: Cao Xiaoxu , Zhao Wei , Zhang He , Lin Jitong , Hu Jingying , Lou Yanhong , Wang Hui , Yang Quangang , Pan Hong , Zhuge Yuping 
Published: December 2022

IntroductionThe large-scale development of animal husbandry and industrialization lead to more and more serious co-contamination from heavy metals and antibiotics in soils. Ecotoxic effects of residues from antibiotics and heavy metals are of increasing concern.Materials and MethodsIn this study, oxytetracycline (OTC) and cadmium (Cd) were selected as target pollutants to evaluate the individual and combined effects on nitrification process using four different soil types sampled from North to South China through a 56-day incubation experiment.Results and DiscussionThe results demonstrated that the contaminations of OTC and Cd, especially combined pollution had significant inhibitory effects on net nitrification rates (NNRs) as well as on AOA and AOB abundance. The toxic effects of contaminants were greatly enhanced with increasing OTC concentration. AOB was more sensitive than AOA to exogenous contaminants. And the interaction effects of OTC and Cd on ammonia oxidizers were mainly antagonistic. Furthermore, Cd contaminant (with or without OTC) had indirect effects on nitrification activity via inhibiting mineral N and AOA/AOB, while OTC alone indirectly inhibited nitrification activity by inhibiting ammonia oxidizers. The results could provide theoretical foundation for exploring the eco-environmental risks of antibiotics and heavy metals, as well as their toxic effects on nitrification processes.
Alpha retinal ganglion cells in pigmented mice retina: number and distribution
Authors: Gallego-Ortega Alejandro , Norte-Muñoz María , Di Pierdomenico Johnny , Avilés-Trigueros Marcelino , de la Villa Pedro , Valiente-Soriano Francisco Javier , Vidal-Sanz Manuel 
Published: December 2022

Purpose: To identify and characterize numerically and topographically the population of alpha retinal ganglion cells (αRGCs) and their subtypes, the sustained-response ON-center αRGCs (ONs-αRGCs), which correspond to the type 4 intrinsically photosensitive RGCs (M4-ipRGCs), the transient-response ON-center αRGCs (ONt-αRGCs), the sustained-response OFF-center αRGCs (OFFs-αRGCs), and the transient-response OFF-center αRGCs (OFFt-αRGCs) in the adult pigmented mouse retina.Methods: The αRGC population and its subtypes were studied in flat-mounted retinas and radial sections immunodetected against non-phosphorylated high molecular weight neurofilament subunit (SMI-32) or osteopontin (OPN), two αRGCs pan-markers; Calbindin, expressed in ONs-αRGCs, and amacrines; T-box transcription factor T-brain 2 (Tbr2), a key transcriptional regulator for ipRGC development and maintenance, expressed in ipRGCs and GABA-displaced amacrine cells; OPN4, an anti-melanopsin antibody; or Brn3a and Brn3c, markers of RGCs. The total population of RGCs was counted automatically and αRGCs and its subtypes were counted manually, and color-coded neighborhood maps were used for their topographical representation.Results: The total mean number of αRGCs per retina is 2,252 ± 306 SMI32+αRGCs and 2,315 ± 175 OPN+αRGCs (n = 10), representing 5.08% and 5.22% of the total number of RGCs traced from the optic nerve, respectively. αRGCs are distributed throughout the retina, showing a higher density in the temporal hemiretina. ONs-αRGCs represent ≈36% [841 ± 110 cells (n = 10)] of all αRGCs and are located throughout the retina, with the highest density in the temporal region. ONt-αRGCs represent ≈34% [797 ± 146 cells (n = 10)] of all αRGCs and are mainly located in the central retinal region. OFF-αRGCs represent the remaining 32% of total αRGCs and are divided equally between OFFs-αRGCs and OFFt-αRGCs [363 ± 50 cells (n = 10) and 376 ± 36 cells (n = 10), respectively]. OFFs-αRGCs are mainly located in the supero-temporal peripheral region of the retina and OFFt-αRGCs in the mid-peripheral region of the retina, especially in the infero-temporal region.Conclusions: The combination of specific antibodies is a useful tool to identify and study αRGCs and their subtypes. αRGCs are distributed throughout the retina presenting higher density in the temporal area. The sustained ON and OFF response subtypes are mainly located in the periphery while the transient ON and OFF response subtypes are found in the central regions of the retina.
Prognostic value of susceptibility-weighted imaging of prominent veins in acute ischemic stroke: A systematic review and meta-analysis
Authors: Xiang Wei , Liang Zhigang , Zhang Manman , Wei Hongchun , Sun Zhongwen , Lv Yaodong , Meng Yuedan , Li Wei , Zheng Huaguang , Zhang Hongxia 
Published: December 2022

BackgroundThe prominent veins sign (PVS) on susceptibility-weighted imaging (SWI) has been suggested to be related to the prognosis of patients with acute ischemic stroke (AIS). This meta-analysis aims to clarify the association between PVS and the prognosis of patients with AIS.MethodsThis meta-analysis was registered in PROSPERO (no. CRD42022343795). We performed systematic research in PubMed, Web of Science, EMBASE, and Cochrane Library databases for studies investigating the prognostic value of PVS. Based on the enrolled studies, patients were divided into two groups as follows: those with PVS cohort and those without PVS cohort. Outcomes were unfavorable functional outcome, early neurological deterioration (END), and hemorrhagic transformation (HT). The random-effects models were used for the meta-analytical pooled. Heterogeneity was estimated using Cochran's Q-test and I2 value. Subgroup and sensitivity analyses were also performed to explore the potential sources of heterogeneity. Publication bias was assessed with funnel plots and using Begger's and Egger's tests.ResultsA total of 19 studies with 1,867 patients were included. PVS was correlated with an unfavorable functional outcome in patients with AIS (risk ratio [RR] 1.61, 95% CI 1.28–2.02), especially in those receiving recanalization therapy (RR 2.00, 95% CI 1.52–2.63), but not in those treated conservatively (RR 1.33, 95% CI 0.87–2.04). Moreover, PVS was related to END (RR 2.77, 95% CI 2.21–3.46), while without an increased risk of HT (RR 0.97, 95% CI 0.64–1.47).ConclusionPVS was associated with an unfavorable prognosis of patients with AIS and increased the risk of END, while not correlated with an increased risk of HT. PVS might be useful for predicting functional outcomes of patients with AIS as a novel imaging maker.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022343795.
Neurodevelopmental outcomes and volumetric analysis of brain in preterm infants with isolated cerebellar hemorrhage
Authors: Kim Seh Hyun , Shin Seung Han , Yang Hyo Ju , Park Seul Gi , Lim Soo Yeon , Choi Young Hun , Kim Ee-Kyung , Kim Han-Suk 
Published: December 2022

BackgroundCerebellar hemorrhage (CBH) is a major form of cerebellar injury in preterm infants. We aimed to investigate the risk factors and neurodevelopmental outcomes of isolated CBH and performed volumetric analysis at term-equivalent age.MethodsThis single-centered nested case-control study included 26 preterm infants with isolated CBH and 52 infants without isolated CBH and any significant supratentorial injury.ResultsIsolated CBH was associated with PCO2 fluctuation within 72 h after birth (adjusted odds ratio 1.007, 95% confidence interval 1.000–1.014). The composite score in the motor domain of the Bayley Scales of Infant and Toddler Development at 24 month of corrected age was lower in the punctate isolated CBH group than that in the control group (85.3 vs. 94.5, P = 0.023). Preterm infants with isolated CBH had smaller cerebellum and pons at term-equivalent age compared to the control group. Isolated CBH with adverse neurodevelopment had a smaller ventral diencephalon and midbrain compared to isolated CBH without adverse neurodevelopmental outcomes.ConclusionsIn preterm infants, isolated CBH with punctate lesions were associated with abnormal motor development at 24 months of corrected age. Isolated CBH accompanied by a smaller ventral diencephalon and midbrain at term equivalent had adverse neurodevelopmental outcomes.
Acupuncture decreases amygdala functional connectivity in subjective tinnitus
Authors: Zhang Yating , Zha Bixiang , Shi Haiping , Cheng Ling , Fan Yinqiu , Zhang Wanlin , Rong Zhihao , Jin Zhaoxing , Gao Nan , Yang Jun , Zhang Qingping 
Published: December 2022

IntroductionSubjective tinnitus is a common and intractable ear disease. The effectiveness of acupuncture in the treatment of subjective tinnitus has been confirmed, but its mechanism of action is not clear. The structures of the amygdala (AMYG) are mainly closely related to emotion in the human brain. This study aimed to investigate the changes in functional connectivity (FC) of AMYG in subjective tinnitus to elucidate the neural mechanism of acupuncture.MethodsCorrelation scale scores of 26 patients with subjective tinnitus were collected, including Tinnitus Evaluation Questionnaire (TEQ), Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS). Meanwhile, rs-fMRI data were collected before and after acupuncture treatment in the patients, and in healthy controls (HC) matching the patient's gender and age. Then, AMYG was selected as region of interest to perform FC analysis. Finally, FC patterns of AMYG were first compared between patients with subjective tinnitus and HC, and then within subjects pre-acupuncture and post-acupuncture. Simple linear regression models between correlation scale scores and FC-values were established as well.ResultsAcupuncture treatment relieved the severity of tinnitus. With the acupuncture treatment, the total THI score, TEQ score, and VSA score of patients were significantly lower than before (p &lt; 0.05). Compared with HC, FC of tinnitus patients between AMYG and right inferior temporal gyrus and right precuneus significantly decreased before acupuncture (voxel p &lt; 0.001, cluster p &lt; 0.05, corrected with GRF), while FC of tinnitus patients between AMYG and left superior frontal gyrus and right superior temporal gyrus significantly decreased after acupuncture treatment (voxel p &lt; 0.001, cluster p &lt; 0.05, corrected with GRF). FC of tinnitus patients between the AMYG and right superior frontal gyrus and left paracingulate gyrus showed significant decrease after acupuncture treatment (voxel p &lt; 0.001, cluster p &lt; 0.05, corrected with GRF). Besides, the linear regression models of the effect of THI on FC and VAS on FC performed were statistically significant (p &lt; 0.05).DiscussionThe findings demonstrate that acupuncture can decrease FC of AMYG, which could be positively correlated with the relief of tinnitus symptoms. This result suggests that acupuncture stimulation can effectively relieve the severity of tinnitus by decreasing FC of AMYG in subjective tinnitus patients.
High-pressure treatment enhanced aromatic compound concentrations of melon juice and its mechanism
Authors: Liu Xiao , Wang Ruiqi , Liu He , Wang Yubin , Shi Yue , Zhang Chao 
Published: December 2022

IntroductionThe flavor deterioration blocks the development of melon juice.MethodsThe effects of ultra-high temperature (UHT) and high pressure (HP) treatments on the aromatic compound concentrations of melon juice and their mechanisms were explored with fresh juice as the control.ResultsA total of 57 volatile compounds were identified by gas chromatography-tandem mass spectrometry analysis. β-ionone was shown to be the major aromatic component of melon juice for the first time. The HP at 200 MPa for 20 min increased the total volatile concentration of melon juice by 1.54 and 3.77 times the control and UHT, respectively. Moreover, the sum concentration of a major aromatic component in the HP treatment was 1.49 and 5.94 times higher than that of the control and UHT, respectively.DiscussionThe HP treatment raised the concentration of volatile and aromatic components of melon juice by reducing their surface tension.
IL-1β enhances cell viability and decreases 5-FU sensitivity in novel colon cancer cell lines derived from African American patients
Authors: Spagnardi Marzia , Paredes Jenny , Zabaleta Jovanny , Garai Jone , Reyes Tiana , Martello Laura A. , Williams Jennie L. 
Published: December 2022

BackgroundIn the U.S., African Americans (AAs) present with the highest incidence and mortality rates for Colorectal Cancer (CRC). When compared to Caucasian American (CA) patients, AAs also have reduced response to the first line standard of care chemotherapeutic agent 5-Fluorouracil (5-FU). Previously, we observed differential gene expression between the two populations, suggesting that colon tumors from AA patients display a decreased antitumor immune response and an increased expression of genes encoding proteins involved in inflammatory processes, such as Interleukin-1β (IL-1β). Here, we investigate the role of IL-1β in modifying chemotherapeutic response and altering expression of proteins in novel AA and well-established CA colon cancer cell lines.MethodsRNA sequencing analysis was performed to detect expression of genes involved in inflammation in AA and CA colon cancer cells. The effects of IL-1β on 5-FU response was evaluated by assessing cell viability (MTS assay) and apoptosis (flow cytometry analysis) following treatment with 5-FU alone or in combination with the cytokine. Further, we used an IL-1 receptor antagonist (IL-1Ra) to inhibit IL-1β-induced effects on 5-FU sensitivity and NF-kB pathway activation.ResultsAA colon cancer cell lines present significant increase in expression of genes IL1R2 (373-fold change (FC), IRAK1 (3.24 FC), IKBKB, (5.33 FC) NF-KB IA (5.95 FC), MYD88, (3.72 FC), IRAK3 (161 FC), TRAF5 (4.1 FC). A significant decrease in the response to 5-FU treatment, as well as a significant increase in phosphorylation of IκBα and secretion of IL-8, was seen following IL-1β treatment, in both AA and CA cell lines. Finally, treatment with IL-1Ra was able to reverse the effects induced by IL-1β, by increasing the cells sensitivity to 5-FU. IL-1Ra also inhibited phosphorylation of IκBα and IL-8 secretion.ConclusionsOur results suggest a differential expression of inflammatory genes and proteins that might regulate the different response to IL-1β between AA and CA colon cancer cell lines. Our data also demonstrates that IL-1β is involved in modulating 5-FU response in both AA and CA colon cancer cell lines. Further investigation of these mechanisms might help elucidate the differences seen in incidence, mortality and response to therapy in AA colon cancer patients.
An autophagy-related four-lncRNA signature helps to predict progression-free survival of neuroblastoma patients
Authors: Wang Jing , Meng Xinyao , Chen Ke , Feng Jiexiong 
Published: December 2022

BackgroundThis study aimed to identify autophagy-related long non-coding RNAs (lncRNAs) associated with progression of neuroblastoma (NB), and to build an autophagy-related lncRNA signature that helps to predict progression-free survival (PFS) of NB.MethodsThree independent gene expression datasets were utilized in this study. Autophagy-related genes (ARG) associated with PFS of NB patients were firstly identified by univariate Cox survival analysis. lncRNAs correlated with those PFS-related ARGs were then identified. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to select out those lncRNAs with the best prognostic value for PFS. The Receiver Operating Characteristic (ROC) and Area Under Curve (AUC) analyses were performed to assess the prediction accuracy.ResultsFour autophagy-related lncRNAs (AL356599.1, AC022075.1, AC020928.1 and LINC02076) were found to be with the best prognostic value and integrated into a four-lncRNA risk signature for predicting PFS of NB patients. The four-lncRNA signature significantly stratify NB patients into two risk groups, with high-risk group has significantly poorer PFS than the low-risk group. The prognostic role of the lncRNA signature was independent with other clinical risk factors. The ROC curves revealed that the lncRNA signature has a good performance in predicting PFS (AUC &gt; 0.70). A nomogram based on COG (Children’s Oncology Group) risk and the lncRNA risk score was constructed, showing good prediction accuracy (C-index = 0.700). The prognostic ability of the nomogram was better than that of COG risk alone (AUC = 0.790 versus AUC = 0.748). GSEA analyses revealed that multiple autophagy-related gene sets are significantly enriched in the low-risk group.ConclusionsWe identified an autophagy-related four-lncRNA signature that could help to predict the PFS of NB patients. Autophagy-related gene sets are significantly enriched in low-risk group, suggesting tumor suppressive roles of autophagy in NB.
Weighted gene co-expression network reveals driver genes contributing to phenotypes of anaplastic thyroid carcinoma and immune checkpoint identification for therapeutic targets
Authors: Dong Xingxing , Yang Yalong , Hou Jinxuan , Chen Weizhen , Yuan Qianqian , Xu Gaoran , Liu Jiuyang , Li Chengxin , Wu Gaosong 
Published: December 2022

BackgroundAnaplastic thyroid carcinoma (ATC) is a rare but extremely malignant tumor, with a rapid growth rate and early metastasis thus leading to poor survival of patients. The molecular mechanisms underlying these aggressive traits of ATC remain unknown, which impedes the substantial progress in treatment to prolong ATC patient survival.MethodsWe applied weighted gene co-expression network analysis (WGCNA) to identify ATC-specific modules. The Metascape web and R package clusterProfiler were employed to perform enrichment analysis. Combined with differentially expressed gene analysis, we screened out the most potential driver genes and validated them using receiver operator characteristic (ROC) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry (IHC), and triple immunofluorescence staining.ResultsA gene expression matrix covering 75 normal samples, 83 papillary thyroid carcinoma (PTC), 26 follicular thyroid carcinoma (FTC), 19 poor-differentiated thyroid carcinoma (PDTC), and 41 ATC tissue samples were integrated, based on which we detected three most potential ATC-specific modules and found that hub genes of these modules were enriched in distinct biological signals. Hub genes in the turquoise module were mainly enriched in mitotic cell cycle, tube morphogenesis, and cell differentiation, hub genes in the magenta module were mainly clustered in the extracellular matrix organization, positive regulation of cell motility, and regulation of Wnt signaling pathway, while hub genes in the blue module primarily participated in the inflammatory response, innate immune response, and adaptive immune response. We showed that 9 top genes, 8 transcription factors (TFs), and 4 immune checkpoint genes (ICGs) were differentially expressed in ATC compared to other thyroid samples and had high diagnostic values for ATC, among which, 9 novel ATC-specific genes (ADAM12, RNASE2, CASP5, KIAA1524, E2F7, MYBL1, SRPX2, HAVCR2, and TDO2) were validated with our clinical samples. Furthermore, we illustrated that ADAM12, RNASE2, and HAVCR2 were predominantly present in the cytoplasm.ConclusionOur study identified a set of novel ATC-specific genes that were mainly related to cell proliferation, invasion, metastasis, and immunosuppression, which might throw light on molecular mechanisms underlying aggressive phenotypes of ATC and provide promisingly diagnostic biomarkers and therapeutic targets.
Safety profile of robotic-assisted transperineal MRI-US-fusion guided biopsy of the prostate
Authors: Walter Manuel , Trotsenko Pawel , Breit Hanns-Christian , Keller Nicola , Meyer Anja , Winkel David Jean , Seifert Hans Helge , Wetterauer Christian 
Published: December 2022

IntroductionRobotic-assisted transperineal MRI-US-fusion guided biopsy of the prostate is a novel and highly accurate procedure. The aim of this study was to evaluate the MonaLisa prostate biopsy system in terms of safety, tolerability, and patient-related outcomes.MethodsThis prospective study included 228 patients, who had undergone Robotic-assisted transperineal MRI-US-fusion guided biopsy of the prostate at the University Hospital Basel between January 2020 and June 2022. Peri-operative side effects, functional outcomes and patient satisfaction were assessed.ResultsMean pain score on the day of biopsy was 1.3 points on VAS, which remained constant on the day after biopsy. Overall, 32 of 228 patients (14%) developed grade I complications according to Clavien-Dindo classification. No higher-grade complications occurred. Gross haematuria, hematospermia and acute urinary retention occurred in 145/228 (63.6%), 98/228 (43%) and 32/228 (14%) patients, respectively. One patient (0.4%) developed urinary tract infection.ConclusionsRobotic-assisted transperineal MRI-US-fusion guided biopsy of the prostate performed under general anesthesia is a safe and well tolerated procedure. This technique allows to omit perioperative prophylaxis and at the same time minimizes the risk of infectious complications. We attribute the favorable risk profile and tolerability to the minimal invasive approach via two entry points.