bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of cachexia index in patients with colorectal cancer: A retrospective study
Authors: Wan Qianyi , Yuan Qian , Zhao Rui , Shen Xiaoding , Chen Yi , Li Tao , Song Yinghan 
Published: September 2022

BackgroundCurrent diagnostic criteria for cancer cachexia are inconsistent, and arguments still exist about the impact of cachexia on the survival of patients with colorectal cancer. In this study, we aim to investigate the prognostic value of a novel cachexia indicator, the cachexia index (CXI), in patients with colorectal cancer.MethodsThe CXI was calculated as skeletal muscle index (SMI) × serum albumin/neutrophil-lymphocyte ratio. The cut-off value of CXI was determined by the receiver operating characteristic (ROC) curves and Youden’s index. The major outcomes were major complications, overall survival (OS), and recurrence-free survival (RFS).ResultsA total of 379 patients (234 men and 145 women) were included. The ROC curves indicated that CXI had a significantly diagnostic capacity for the detection of major complications. Based on Youden’s index, there were 231 and 148 patients in the low and high CXI groups, respectively. Patients in the low CXI group had significantly older age, lower BMI, and a higher percentage of cachexia and TNM stage II+III. Besides, Patients in low CXI group were associated with a significantly higher rate of major complications, blood transfusion, and longer length of stay. Logistic regression analysis indicated that low CXI, cachexia, and coronary heart disease were independent risk factors for the major complications. Kaplan Meier survival curves indicated that patients with high CXI had a significantly more favorable OS than those with low CXI, while no significant difference was found in RFS between the two groups. Besides, there were no significant differences in OS or RFS between patients with and without cachexia. The univariate and multivariate Cox regression analysis indicated that older age, low CXI, and coronary heart disease instead of cachexia were associated with a decreased OS.ConclusionCXI was better than cachexia in predicting OS and could be a useful prognostic indicator in patients with colorectal cancer, and greater attention should be paid to patients with low CXI.
A pulmonary enteric adenocarcinoma patient harboring a rare EGFR exon 19 P753S mutation: Case report and review
Authors: Xu Xiaohu , Chen Dong , Wu Xiao , Wang Qi 
Published: September 2022

Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of non–small cell lung cancer (NSCLC), accounting for about 0.6% of all primary lung adenocarcinoma. Although epidermal growth factor receptor (EGFR) mutation is common in primary lung adenocarcinoma, it is rarely reported in PEAC. This case report describes a PEAC patient with co-mutations of EGFR, Kirsten rat sarcoma viral oncogene (KRAS), and TP53, being treated with immunotherapy combined with chemotherapy. A 69-year-old man complained of cough and expectoration with bloody sputum for 2 weeks. The lung-enhanced CT scan showed a massive soft tissue shadow, about 46 × 35 mm in the lower lobe of the right lung. The neoplasm sample in the lower lobe of the right lung was obtained using CT-guided fine-needle aspiration (FNA). Immunohistochemical assays showed that the tumor was positive for CK7, CDX-2, C-MET, and villin. Gastroscopy and rectal colonoscopy had been performed respectively to exclude a diagnosis of colorectal adenocarcinoma. The patient was finally diagnosed with pulmonary intestinal adenocarcinoma. Next-generation sequencing (NGS) analysis showed a rare EGFR exon 19 missense mutation (c.2257C&gt;T, p.P753S), KRAS exon 2 missense mutation (c.35G&gt;T, p.G12V), and TP53 exon 5 missense mutation (c.401T&gt;C, p.F134S). The lung-enhanced CT scan showed that the tumor shrank after four cycles of chemotherapy combined with immunotherapy. We hope that this case report can increase the understanding of this rare type of tumor and provide new molecular indications for diagnosis and individualized treatment. Furthermore, the combination of chemotherapy and immunotherapy seems to be an effective therapy for PEAC. Whether the use of immunotherapy can provide clinical benefits needs to be further explored with more samples in future studies.
HIF-2α regulates proliferation, invasion, and metastasis of hepatocellular carcinoma cells via VEGF/Notch1 signaling axis after insufficient radiofrequency ablation
Authors: Yang Yongguang , Chen Weifeng , Mai Weiheng , Gao Yi 
Published: September 2022

Background and AimsAlthough insufficient radiofrequency ablation (RFA) promotes the recurrence and metastasis of liver cancer, the underlying mechanism remains unclear. This study aimed to investigate the role and mechanism of HIF-2α in hepatocellular carcinoma cells (HCCs) after Insufficient RFA.MethodsWe established a model of insufficient RFA in MHCC97H hepatoma cells and screened for stable sublines. We inhibited HIF-2α expression in the Insufficient RFA group using PT2385 and assessed the resulting changes in proliferation and biological function of HCCs. Cell viability and proliferation were detected by the MTT method, and scratch and Transwell chamber invasion tests detected migration and invasion abilities of HCCs. The mRNA and protein expression levels of VEGF, HIF-2α, and Notch1 were detected using qPCR, immunofluorescence, and western blotting.ResultsCompared with normal HCCs without RFA treatment, insufficient RFA enhanced the proliferation and invasion abilities of hepatocellular carcinoma subline MHCC97H (P &lt; 0.001), as well as their migration ability (P = 0.046). The HIF-2α-specific inhibitor PT2385 downregulated the migration (P = 0.009) and invasion (P &lt; 0.001) of MHCC97H cells but did not affect cell proliferation (P &gt; 0.05). Insufficient ablation increased the mRNA and protein expression of VEGF, HIF-2α, and Notch1 in HCCs, whereas inhibition of HIF-2α reversed these changes.ConclusionsInsufficient RFA increases the proliferation, migration, and invasion of HCCs via the HIF-2α/VEGF/Notch1 signaling axis; HIF-2α is a potential target for novel treatments of HCC after insufficient RFA.
Changes in the incidence of acute bacterial meningitis caused by Streptococcus pneumoniae and the implications of serotype replacement in children in Colombia after mass vaccination with PCV10
Authors: Farfán-Albarracín Juan David , Camacho-Moreno Germán , Leal Aura Lucia , Patiño Jaime , Coronell Wilfrido , Gutiérrez Iván Felipe , Beltrán Sandra , Álvarez-Olmos Martha I. , Mariño Cristina , Barrero Rocio , Rojas Juan Pablo , Espinosa Fabio , Arango-Ferreira Catalina , Suarez Maria Alejandra , Trujillo Monica , López-Medina Eduardo , López Pio , Pinzón Hernando , Ramos Nicolás , Moreno Vivian Marcela , Montañez Anita 
Published: September 2022

IntroductionAcute bacterial meningitis (ABM) is a public health problem. The disease has reemerged after the introduction of pneumococcal conjugate vaccines (PCVs) due to an increase in serotypes that are not covered. The objective was to determine the changes in the disease incidence before and after the introduction of the 10-valent vaccine (PCV10) in Colombia.MethodsThis multicenter study was conducted in 17 hospitals in Colombia. Data were collected from January 2008 to December 2019 in 10 hospitals in Bogotá and from January 2017 to December 2019 in seven hospitals in Cali, Medellín and Cartagena. The data were grouped into three periods: 2008–2011, 2012–2015, and 2016-2019.ResultsOf the 706 cases of invasive pneumococcal disease, 81 (11.4%) corresponded to meningitis. The relative incidence in Bogotá in the first period was 0.6 per 100,000 patients ≤ 5 years, decreased to 0.4 per 100,000 patients ≤ 5 years in the second period and increased in the third period to 0.7 per 100,000 patients ≤ 5 years. Serotypes covered by PCV10 decreased from 75 to 9.1%, with Spn19A (31.8%) and Spn34 (13.6%) emerging in the third period. Increased resistance to penicillin (13 to 37%) and to ceftriaxone (5.9 to 16%) was due to the emergence of multidrug-resistant Spn19A. The total mortality rate was 23.5% and increased from 12 to 33%.ConclusionsABM due to pneumococcus has high morbidity and mortality rates. Reemergence of the disease has been observed due to the inclusion of polymerase chain reaction (PCR) for diagnosis and replacement of circulating serotypes after the introduction of PCV10, with an increase in Spn19A, which causes death and exhibits antimicrobial resistance. Continued surveillance is needed.
Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes
Authors: Zhang Juan-juan , Wang Jun-qi , Xu Xu , Zhang Li-dan , Zhang Cai-ping , Lu Wen-li , Gu Wei-qiong , Dong Zhi-ya , Xiao Yuan , Xia Zhen-wei 
Published: September 2022

IntroductionThe frequency of celiac disease autoantibody (CDAb) positivity in type 1 diabetes (T1D) has increased due to unclear mechanisms, including autoimmune injury. Circular ribonucleic acids (circRNAs) participate in autoimmune diseases, but the roles of circRNAs in T1D with CDAbs are currently unknown. This study aimed to determine the frequency of CDAbs in Chinese children with T1D and describe the relationship between CDAbs and circRNAs.Materials and methodsEighty patients diagnosed with T1D were screened for CDAbs and CD-predisposing genes, and circRNAs in peripheral blood mononuclear cells (PBMCs) were collected from 47 patients. The Gene Expression Omnibus (GEO) database was searched for candidate circRNAs in related studies on T1D PBMCs. Data on clinical characteristics (i.e., blood glucose control, residual islet function, and daily insulin dosage) and immunophenotypes (i.e., islet autoantibodies and immune cell subsets) were collected.ResultsIn total, 35.0% of patients were positive for CDAbs. CD-predisposing genes accounted for 52.5% of the genes, and no significant difference in frequency was found between the CDAb-positive (CDAb+) and CDAb-negative (CDAb–) groups. In addition, among the differentially expressed circRNAs from the GEO database, five highly conserved circRNAs homologous to humans and mice were screened, and only the expression of hsa_circ_0004564 in the CDAb+ group significantly decreased (CDAb+ vs. CDAb–:1.72 ± 1.92 vs. 11.12 ± 8.59, p = 6.0 × 10–6), while the expression of hsa_circ_0004564 was upregulated in the general T1D population. Moreover, its parental gene RAPH1 was significantly upregulated (CDAb+ vs. CDAb–:1.26 ± 0.99 vs. 0.61 ± 0.46, p = 0.011). Importantly, the positive correlation between hsa_circ_0004564 and CD3+ cells was validated in children with T1D after adjustments for CDAbs (p = 0.029), while there were no correlations between hsa_circ_0004564 and clinical characteristics or other immune cell subsets (i.e., CD4+ T cells, CD8+ T cells, and natural killer cells).ConclusionThis study highlights the importance of screening for CD in Chinese children with T1D, considering the high prevalence of CDAb positivity and CD-predisposing genes. The profile of candidate circRNAs in children with T1D with CDAbs was different from that in previous reports on general T1D patients from the GEO database. Moreover, hsa_circ_0004564 and its parental gene RAPH1 may be new targets for studying immune mechanisms in children with T1D and CD.
The exploration of the potential mechanism of oxymatrine-mediated antipruritic effect based on network pharmacology and weighted gene co-expression network analysis
Authors: Luo Zhenhui , Zhao Tingting , Yi Mengqin , Wang Tingting , Zhang Zhenglang , Li Wenbin , Lin Na , Liang Shangdong , Verkhratsky Alexei , Nie Hong 
Published: September 2022

The treatment of chronic itch is considered to be a challenge for its non-histamine dependence and the search for alternative medicine is still striving. The pathology of the chronic itch is closely related to immune system regulation and inflammatory response. Oxymatrine (OMT) is a traditional Chinese medicine ingredient extracted from the roots of Sophora flavescens Aiton with significant antitumor, analgesic, and anti-inflammatory effects. However, the underlying mechanism of OMT on chronic itch is obscure, which limits clinical application. Hence, this study is aimed to clarify the pruritus alleviation mechanism of OMT by combining network pharmacology analysis, weighted gene co-expression analysis (WGCNA), and molecular docking. We screened 125 common targets of OMT regulating inflammation and pruritus with pharmacology technology, the GO enrichment function analysis and KEGG signaling pathway analysis to demonstrate the close relation to the signaling pathways regulating inflammation such as MAPK signaling pathway and PI3K-AKT signaling pathway. We adopted the most relevant templates for pruritus diseases, combined with network pharmacology to preliminarily screen out 3 OMT functions and regulatory targets, exerting a good connection and correlation with the target at the screened disease targets. Further experiments were conducted to explore the potential mechanism of OMT using the LPS-induced RAW264.7 cell inflammation model. The results showed that pretreatment with different concentrations of OMT (25 μM, 50 μM, and 100 μM) for 24 h, inhibited expression of IL-6, iNOS TLR4 and TGFR-1 as well as apoptosis of Raw264.7 cells induced by LPS. Moreover, OMT effectively inhibited LPS-induced MAPK pathway activation and the expression of related sites MAP2K1, MAPK8 MAP2K4, and MAPKAP-K2 in RAW 264.7 cells. The OMT also reduced the phosphorylation of p-38, associated with site in the activation of MAPK signaling pathway. These results could contribute to a better understanding of the mechanisms underlying how OMT alleviates inflammation to treat chronic pruritic diseases and provide a potential drug for the treatment of chronic itch.
Detection of pediatric drug-induced kidney injury signals using a hospital electronic medical record database
Authors: Yu Yuncui , Nie Xiaolu , Zhao Yiming , Cao Wang , Xie Yuefeng , Peng Xiaoxia , Wang Xiaoling 
Published: September 2022

Background: Drug-induced kidney injury (DIKI) is one of the most common complications in clinical practice. Detection signals through post-marketing approaches are of great value in preventing DIKI in pediatric patients. This study aimed to propose a quantitative algorithm to detect DIKI signals in children using an electronic health record (EHR) database.Methods: In this study, 12 years of medical data collected from a constructed data warehouse were analyzed, which contained 575,965 records of inpatients from 1 January 2009 to 31 December 2020. Eligible participants included inpatients aged 28 days to 18 years old. A two-stage procedure was adopted to detect DIKI signals: 1) stage 1: the suspected drugs potentially associated with DIKI were screened by calculating the crude incidence of DIKI events; and 2) stage 2: the associations between suspected drugs and DIKI were identified in the propensity score-matched retrospective cohorts. Unconditional logistic regression was used to analyze the difference in the incidence of DIKI events and to estimate the odds ratio (OR) and 95% confidence interval (CI). Potentially new signals were distinguished from already known associations concerning DIKI by manually reviewing the published literature and drug instructions.Results: Nine suspected drugs were initially screened from a total of 652 drugs. Six drugs, including diazepam (OR = 1.61, 95%CI: 1.43–1.80), omeprazole (OR = 1.35, 95%CI: 1.17–1.54), ondansetron (OR = 1.49, 95%CI: 1.36–1.63), methotrexate (OR = 1.36, 95%CI: 1.25–1.47), creatine phosphate sodium (OR = 1.13, 95%CI: 1.05–1.22), and cytarabine (OR = 1.17, 95%CI: 1.06–1.28), were demonstrated to be associated with DIKI as positive signals. The remaining three drugs, including vitamin K1 (OR = 1.06, 95%CI: 0.89–1.27), cefamandole (OR = 1.07, 95%CI: 0.94–1.21), and ibuprofen (OR = 1.01, 95%CI: 0.94–1.09), were found not to be associated with DIKI. Of these, creatine phosphate sodium was considered to be a possible new DIKI signal as it had not been reported in both adults and children previously. Moreover, three other drugs, namely, diazepam, omeprazole, and ondansetron, were shown to be new potential signals in pediatrics.Conclusion: A two-step quantitative procedure to actively explore DIKI signals using real-world data (RWD) was developed. Our findings highlight the potential of EHRs to complement traditional spontaneous reporting systems (SRS) for drug safety signal detection in a pediatric setting.
The microtubule network enables Src kinase interaction with the Na,K-ATPase to generate Ca2+ flashes in smooth muscle cells
Authors: Rognant Salomé , Kravtsova Violetta V. , Bouzinova Elena V. , Melnikova Elizaveta V. , Krivoi Igor I. , Pierre Sandrine V. , Aalkjaer Christian , Jepps Thomas A. , Matchkov Vladimir V. 
Published: September 2022

Background: Several local Ca2+ events are characterized in smooth muscle cells. We have previously shown that an inhibitor of the Na,K-ATPase, ouabain induces spatially restricted intracellular Ca2+ transients near the plasma membrane, and suggested the importance of this signaling for regulation of intercellular coupling and smooth muscle cell contraction. The mechanism behind these Na,K-ATPase-dependent “Ca2+ flashes” remains to be elucidated. In addition to its conventional ion transport function, the Na,K-ATPase is proposed to contribute to intracellular pathways, including Src kinase activation. The microtubule network is important for intracellular signaling, but its role in the Na,K-ATPase-Src kinase interaction is not known. We hypothesized the microtubule network was responsible for maintaining the Na,K-ATPase-Src kinase interaction, which enables Ca2+ flashes.Methods: We characterized Ca2+ flashes in cultured smooth muscle cells, A7r5, and freshly isolated smooth muscle cells from rat mesenteric artery. Cells were loaded with Ca2+-sensitive fluorescent dyes, Calcium Green-1/AM and Fura Red/AM, for ratiometric measurements of intracellular Ca2+. The Na,K-ATPase α2 isoform was knocked down with siRNA and the microtubule network was disrupted with nocodazole. An involvement of the Src signaling was tested pharmacologically and with Western blot. Protein interactions were validated with proximity ligation assays.Results: The Ca2+ flashes were induced by micromolar concentrations of ouabain. Knockdown of the α2 isoform Na,K-ATPase abolished Ca2+ flashes, as did inhibition of tyrosine phosphorylation with genistein and PP2, and the inhibitor of the Na,K-ATPase-dependent Src activation, pNaKtide. Ouabain-induced Ca2+ flashes were associated with Src kinase activation by phosphorylation. The α2 isoform Na,K-ATPase and Src kinase colocalized in the cells. Disruption of microtubule with nocodazole inhibited Ca2+ flashes, reduced Na,K-ATPase/Src interaction and Src activation.Conclusion: We demonstrate that the Na,K-ATPase-dependent Ca2+ flashes in smooth muscle cells require an interaction between the α2 isoform Na, K-ATPase and Src kinase, which is maintained by the microtubule network.
Heat-shock and methyl-jasmonate: The cultivar-specific responses of pepper plants
Authors: Otálora Ginés , Piñero María Carmen , Collado-González Jacinta , Gálvez Amparo , López-Marín Josefa , del Amor Francisco M. 
Published: September 2022

Frequency, intensity and duration heat-related events have profound implications for future food supply through effects on plant growth and development. This concern needs effective and urgent mitigation tools. However, the effectiveness of potential solutions may decrease according to the specific cultivar response rather consider at specie level. The metyl-jasmonates are essential cellular regulators which are involved in pivotal plant development processes and related to confer protection to heat shock. Thus, our aim was to study the response of three pepper cultivars, Agio (Hungarian type), Basque (Chilli type), and Loreto (Lamuyo type), subjected to heat shock (40°C/72 h) and foliarly-sprayed with methyl-jasmonate (MeJA; 100 µmol), and the effects on several physiological traits. Our results show that despite the important differential impact of heat shock caused on each cultivar, MeJA application did not affect gas exchange, chlorophyll A concentration or efficiency of the photosystem in these cultivars. However, P concentration was reduced when MeJA was applied to Basque chilli, and a significant effect on leaf carbohydrates concentration was observed for Agio and Loreto. Moreover, Agio was the only cultivar in which the amino-acid profile was affected by MeJA under heat shock. Under that condition, putrescine increased for all cultivars, whist the effect of MeJA was only observed for spermine and histamine for Agio and Loreto. Thus, the results indicated that the ameliorative impact of MeJA on this stressor was clearly influenced by cultivar, revealing specific traits. Thus, these results could be used as valuable tools for the characterization of this intraspecific tolerance to heat shock during the vegetative growth stage of pepper.
The Influence of Preoperative Mood and Treatment Expectations on Early Postsurgical Acute Pain After a Total Knee Replacement
Authors: Stuhlreyer Julia , Klinger Regine 
Published: September 2022

BackgroundReducing postoperative pain immediately after surgery is crucial because severe postoperative pain reduces quality of life and increases the likelihood that patients develop chronic pain. Even though postoperative pain has been widely studied and there are national guidelines for pain management, the postoperative course is differently from one patient to the next. Different postoperative courses could be explained by factors related to the treatment context and the patients. Preoperative emotional states and treatment expectations are significant predictors of postoperative pain. However, the interaction between emotional states and preoperative treatment expectations and their effect on postoperative pain have not yet been studied. The aim of our study was to identify the interaction between emotional states, treatment expectation and early postsurgical acute pain.MethodsIn this prospective clinical trial, we enrolled patients who had received a TKR at a German hospital between October 2015 and March 2019. Patients rated their preoperative pain on a numeric rating scale (NRS) 0–10 (0 = no pain and 10 = worst pain imaginable), their emotional states preoperatively on the Pain and State of Health Inventory (PHI), their preoperative treatment expectations on the Stanford Expectation of Treatment Scale (SETS), and their postoperative level of pain on a NRS 0–10.FindingsThe questionnaires were completed by 122 patients (57% female). Emotional states predict negative treatment expectation F(6, 108) = 8.32, p &lt; 0.001, with an excellent goodness-of-fit, R2 = 0.31. Furthermore, a mediator analysis revealed that the indirect effects and therefore relationship between the emotional states sad (ab = 0.06, 95% CI[0.01, 0.14]), anxious (ab = 0.13, 95% CI[0.04, 0.22]), and irritable (ab = 0.09, 95% CI[0.03, 0.17]) and postoperative pain is fully mediated by negative treatment expectations. Whereas the emotional states tired (ab = 0.09, 95% CI[0.03, 0.17]), dizzy/numb (ab = 0.07, 95% CI[0.01, 0.20]), weak (ab = 0.08, 95% CI[0.03, 0.16] are partially mediated by negative treatment expectations.ConclusionThe relationship between emotional states and postoperative pain is mediated by negative treatment expectations. Therefore, innovative treatment strategies to reduce postoperative pain should focus on eliminating negative treatment expectation through establishing a differentiated preoperative expectation management program that also focuses on emotional states.