bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of risk factors for lymph node metastasis and prognosis study in patients with early gastric cancer: A SEER data-based study
Authors: Li Jinzhou , Cui Ting , Huang Zeping , Mu Yanxi , Yao Yalong , Xu Wei , Chen Kang , Liu Haipeng , Wang Wenjie , Chen Xiao 
Published: March 2023

BackgroundLymph node status is an important factor in determining the prognosis of patients with early gastric cancer (EGC) and preoperative diagnosis of lymph node metastasis (LNM) has some limitations. This study explored the risk factors and independent prognostic factors of LNM in EGC patients and constructed a clinical prediction model to predict LNM.MethodsClinicopathological data of EGC patients was collected from the public Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression was used to identify risk factors for LNM in EGC patients. The performance of the LNM model was evaluated by C-index, calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA) curve, and clinical impact curve (CIC) based on the results of multivariate regression to develop a nomogram. An independent data set was obtained from China for external validation. The Kaplan-Meier method and Cox regression model were used to identify potential prognostic factors for overall survival (OS) in EGC patients.ResultsA total of 3993 EGC patients were randomly allocated to a training cohort (n=2797) and a validation cohort (n=1196). An external cohort of 106 patients from the Second Hospital of Lanzhou University was used for external validation. Univariate and multivariate logistic regression showed that age, tumor size, differentiation, and examined lymph nodes count (ELNC) were independent risk factors for LNM. Nomogram for predicting LNM in EGC patients was developed and validated. The predictive model had a good discriminatory performance with a concordance index (C-index) of 0.702 (95% CI: 0.679-0.725). The calibration plots showed that the predicted LNM probabilities were the same as the actual observations in both the internal validation cohort and external validation cohort. The AUC values for the training cohort, internal validation cohort and external validation cohort were 0.702 (95% CI: 0.679-0.725), 0.709 (95% CI: 0.674-0.744) and 0.750(95% CI: 0.607-0.892), respectively, and the DCA curves and CIC showed good clinical applicability. The Cox regression model identified age, sex, race, primary site, size, pathological type, LNM, distant metastasis, and ELNC were prognostic factors for OS in EGC patients, while a year at diagnosis, grade, marital status, radiotherapy, and chemotherapy were not independent prognostic factors.ConclusionIn this study, we identified risk factors and independent prognostic factors for the development of LNM in EGC patients, and developed a relatively accurate model to predict the development of LNM in EGC patients.
Toripalimab in combination with Anlotinib for unresectable hepatocellular carcinoma after SBRT: A prospective, single-arm, single-center clinical study
Authors: Chen Yongbiao , Hong Hanyin , Fang Wenzheng , Zhang Xia , Luo Huachun , Chen Zhijian , Yu Jianda , Fan Weiqiang , Chi Xiaobin , Peng Yonghai 
Published: March 2023

ObjectiveExposing tumor antigens to the immune system is the key to ensuring the efficacy of immunotherapy. SBRT is the main way to reveal the specifical antigens of tumors which can enhance the immune response. We aimed to explore the clinical efficacy and safety of Toripalimab combined with Anlotinib for uHCC after SBRT.MethodsThis is a prospective, single-arm, explorative clinical study. uHCC patients with an ECOG PS score of 0–1, Child–Pugh class A or B, and BCLC stage B or C were included and treated with SBRT(8Gy*3) followed by 6-cycle combinational therapy with Toripalimab and Anlotinib. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of treatment-related adverse events (TRAEs). Continuous variables were presented as medians and ranges. Survivals were studied with the Kaplan-Meier method. Categorical data were expressed as n (percentage).ResultsBetween June 2020 and October 2022, a total of 20 patients with intermediate-advanced uHCC were enrolled. All cases had multiple intrahepatic metastases, or macrovascular invasion, or both, among whom 5 cases with lymph node or distant metastases. Until September 2022, the median follow-up time was 7.2 months (range, 1.1-27.7 months). Median survival time could not be assessed at the moment, based on iRecist, median PFS was 7.4 months (range, 1.1-27.7 months), ORR 15.0%, and DCR 50.0%. 14 patients experienced treatment-related adverse events with an incidence of 70%. The overall survival rates at 18 months and 24 months were 61.1% and 50.9%, respectively. And the progression-free survival rates were 39.3% and 19.7%.ConclusionExposure of specific antigens of HCC via SBRT may improve the efficacy of combinational therapy with Toripalimab and Anlotinib for uHCC with manageable adverse effects, which deserves further exploration.Clinical trial registrationwww.clinicaltrials.gov, identifier ChiCTR2000032533.
Elevated temperatures and longer durations improve the efficacy of oxaliplatin- and mitomycin C-based hyperthermic intraperitoneal chemotherapy in a confirmed rat model for peritoneal metastasis of colorectal cancer origin
Authors: Helderman Roxan F. C. P. A. , Bokan Bella , van Bochove Gregor G. W. , Rodermond Hans M. , Thijssen Elsy , Marchal Wouter , Torang Arezo , Löke Daan R. , Franken Nicolaas A. P. , Kok H. Petra , Tanis Pieter J. , Crezee Johannes , Oei Arlene L. 
Published: March 2023

IntroductionIn patients with limited peritoneal metastasis (PM) originating from colorectal cancer, cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment option. This combined treatment modality using HIPEC with mitomycin C (MMC) for 90 minutes proved to be superior to systemic chemotherapy alone, but no benefit of adding HIPEC to CRS alone was shown using oxaliplatin-based HIPEC during 30 minutes. We investigated the impact of treatment temperature and duration as relevant HIPEC parameters for these two chemotherapeutic agents in representative preclinical models. The temperature- and duration- dependent efficacy for both oxaliplatin and MMC was evaluated in an in vitro setting and in a representative animal model.MethodsIn 130 WAG/Rij rats, PM were established through i.p. injections of rat CC-531 colon carcinoma cells with a signature similar to the dominant treatment-resistant CMS4 type human colorectal PM. Tumor growth was monitored twice per week using ultrasound, and HIPEC was applied when most tumors were 4-6 mm. A semi-open four-inflow HIPEC setup was used to circulate oxaliplatin or MMC through the peritoneum for 30, 60 or 90 minutes with inflow temperatures of 38°C or 42°C to achieve temperatures in the peritoneum of 37°C or 41°C. Tumors, healthy tissue and blood were collected directly or 48 hours after treatment to assess the platinum uptake, level of apoptosis and proliferation and to determine the healthy tissue toxicity.ResultsIn vitro results show a temperature- and duration- dependent efficacy for both oxaliplatin and MMC in both CC-531 cells and organoids. Temperature distribution throughout the peritoneum of the rats was stable with normothermic and hyperthermic average temperatures in the peritoneum ranging from 36.95-37.63°C and 40.51-41.37°C, respectively. Treatments resulted in minimal body weight decrease (&lt;10%) and only 7/130 rats did not reach the endpoint of 48 hours after treatment.ConclusionsBoth elevated temperatures and longer treatment duration resulted in a higher platinum uptake, significantly increased apoptosis and lower proliferation in PM tumor lesions, without enhanced normal tissue toxicity. Our results demonstrated that oxaliplatin- and MMC-based HIPEC procedures are both temperature- and duration-dependent in an in vivo tumor model.
BRCA1-methylated triple negative breast cancers previously exposed to neoadjuvant chemotherapy form RAD51 foci and respond poorly to olaparib
Authors: Velazquez Carolina , Orhan Esin , Tabet Imene , Fenou Lise , Orsetti Béatrice , Adélaïde José , Guille Arnaud , Thézénas Simon , Crapez Evelyne , Colombo Pierre-Emmanuel , Chaffanet Max , Birnbaum Daniel , Sardet Claude , Jacot William , Theillet Charles 
Published: March 2023

BackgroundAbout 15% of Triple-Negative-Breast-Cancer (TNBC) present silencing of the BRCA1 promoter methylation and are assumed to be Homologous Recombination Deficient (HRD). BRCA1-methylated (BRCA1-Me) TNBC could, thus, be eligible to treatment based on PARP-inhibitors or Platinum salts. However, their actual HRD status is discussed, as these tumors are suspected to develop resistance after chemotherapy exposure.MethodsWe interrogated the sensitivity to olaparib vs. carboplatin of 8 TNBC Patient-Derived Xenografts (PDX) models. Four PDX corresponded to BRCA1-Me, of which 3 were previously exposed to NeoAdjuvant-Chemotherapy (NACT). The remaining PDX models corresponded to two BRCA1-mutated (BRCA1-Mut) and two BRCA1-wild type PDX that were respectively included as positive and negative controls. The HRD status of our PDX models was assessed using both genomic signatures and the functional BRCA1 and RAD51 nuclear foci formation assay. To assess HR restoration associated with olaparib resistance, we studied pairs of BRCA1 deficient cell lines and their resistant subclones.ResultsThe 3 BRCA1-Me PDX that had been exposed to NACT responded poorly to olaparib, likewise BRCA1-WT PDX. Contrastingly, 3 treatment-naïve BRCA1-deficient PDX (1 BRCA1-Me and 2 BRCA1-mutated) responded to olaparib. Noticeably, the three olaparib-responsive PDX scored negative for BRCA1- and RAD51-foci, whereas all non-responsive PDX models, including the 3 NACT-exposed BRCA1-Me PDX, scored positive for RAD51-foci. This suggested HRD in olaparib responsive PDX, while non-responsive models were HR proficient. These results were consistent with observations in cell lines showing a significant increase of RAD51-foci in olaparib-resistant subclones compared with sensitive parental cells, suggesting HR restoration in these models.ConclusionOur results thus support the notion that the actual HRD status of BRCA1-Me TNBC, especially if previously exposed to chemotherapy, may be questioned and should be verified using the BRCA1- and RAD51-foci assay.
Human gut, breast, and oral microbiome in breast cancer: A systematic review and meta-analysis
Authors: Thu May Soe , Chotirosniramit Korn , Nopsopon Tanawin , Hirankarn Nattiya , Pongpirul Krit 
Published: March 2023

IntroductionDysbiosis characterises breast cancer through direct or indirect interference in a variety of biological pathways; therefore, specific microbial patterns and diversity may be a biomarker for the diagnosis and prognosis of breast cancer. However, there is still much to determine about the complex interplay of the gut microbiome and breast cancer.ObjectiveThis study aims to evaluate microbial alteration in breast cancer patients compared with control subjects, to explore intestine microbial modification from a range of different breast cancer treatments, and to identify the impact of microbiome patterns on the same treatment-receiving breast cancer patients.MethodsA literature search was conducted using electronic databases such as PubMed, Embase, and the CENTRAL databases up to April 2021. The search was limited to adult women with breast cancer and the English language. The results were synthesised qualitatively and quantitatively using random-effects meta-analysis.ResultsA total of 33 articles from 32 studies were included in the review, representing 19 case-control, eight cohorts, and five nonrandomised intervention researches. The gut and breast bacterial species were elevated in the cases of breast tumours, a significant increase in Methylobacterium radiotolerans (p = 0.015), in compared with healthy breast tissue. Meta-analysis of different α-diversity indexes such as Shannon index (p = 0.0005), observed species (p = 0.006), and faint’s phylogenetic diversity (p &lt; 0.00001) revealed the low intestinal microbial diversity in patients with breast cancer. The microbiota abundance pattern was identified in different sample types, detection methods, menopausal status, nationality, obesity, sleep quality, and several interventions using qualitative analysis.ConclusionsThis systematic review elucidates the complex network of the microbiome, breast cancer, and therapeutic options, with the objective of providing a link for stronger research studies and towards personalised medicine to improve their quality of life.
Adaptations of the Walking Corsi Test (WalCT) for 2- and 3-year-old preterm and term-born toddlers: A preliminary study
Authors: Martín-Pozuelo Nuria , Robles-García Verónica , Piccardi Laura , Quintela del Rio Alejandro , Cudeiro Javier , De las Cuevas-Terán Isabel 
Published: March 2023

IntroductionTopographical memory is crucial for navigation and environmental representation. The Walking Corsi Test (WalCT) has been used to evaluate topographical memory in children from 4 years upward. The present study aims to determine whether adapted versions of the WalCT- by simplifying instructions and increasing motivation- can be adopted to test topographical memory in 2- and 3-year-old toddlers born at term and preterm. Assessing this skill in such young children is important in light of recent studies that have shown how spatial cognition underlies the development of skills in other cognitive domains as well. Methods: For this purpose, 47 toddlers (27.39 ± 4.34 months, 38.3% females), 20 born at term and 27 preterm, performed two aimed-designed versions of WalCT.ResultsThe results showed better performance of the term groups with increasing age and for both versions. On the other hand, performance was better in 2-year-old term toddlers vs. preterm. When rising motivation, 2-year-old preterm toddlers improve their performance but differences between both groups were still significant. The preterm group showed lower performance related to lower levels of attention.DiscussionThis study provides preliminary data on the suitability of the adapted versions of WalCT in early ages and prematurity conditions.
Case report: Progressive skin rash and lymphadenopathy associated with lamotrigine−valproic acid combination in a bipolar adolescent
Authors: Duan Yingxu , Qiu Fangxinrui , Zhou Jingyuan , Liu Shiyu , Zhao Die , Qiu Changjian 
Published: March 2023

Background: Lamotrigine may cause severe skin reactions. There is a known interaction between lamotrigine and valproic acid with an increase in lamotrigine levels and lamotrigine toxicity risk. Few cases of severe rash and systemic reactions in bipolar patients using lamotrigine and valproate have been reported. Here, we report a rare case of severe skin rash and lymphadenopathy associated with lamotrigine−valproic acid combination.Case presentation: An 18-year-old female adolescent with bipolar disorder type I was treated with lamotrigine, magnesium valproate, and perospirone for 12 days. After the last dose of lamotrigine, she abruptly developed generalized rash and swollen lymph nodes, which continued to progress over the next 3 days. This finally subsided after stopping valproate and with glucocorticoid treatment.Conclusion: This case suggests that lamotrigine−valproic acid combination may cause not only rash but also lymphadenopathy. Even though the aforementioned reactions appear after the last dose of lamotrigine, it cannot be ruled out as suspicious. We recommend caution during titration of lamotrigine and valproate and early withdrawal of both when signs of hypersensitivity appear.
Modified 5-aminolevulinic acid photodynamic therapy suppresses cutaneous squamous cell carcinoma through blocking Akt/mTOR-mediated autophagic flux
Authors: Zeng Qingyu , Liu Jia , Yan Yu , Zhang Guolong , Wang Periru , Zhang Haiyan , Liu Xiaojing , Zhang Linglin , Wang Xiuli 
Published: March 2023

Background: We previously found that modified 5-aminolevulinic acid photodynamic therapy (M-PDT) is painless and effective in cutaneous squamous cell carcinoma (cSCC) treatment, however, the regulatory mechanism of M-PDT in cSCC is still unclear.Objective: To clarify the effect and relevant regulatory mechanism of M-PDT in cSCC.Methods: The cSCC apoptosis was examined by flow cytometry, TUNEL staining and Cleaved-caspase-3 immunofluorescence, respectively. The autophagy-related characterization was detected by monodansylcadaverine (MDC) staining, transmission electron microscopy (TEM), GFP-LC3B autophagic vacuoles localization and mRFP-EGFP tandem fluorescence-tagged LC3B construct, respectively. The expression of autophagy-related proteins and Akt/mTOR signaling molecules were examined by Western blot. ROS generation was measured by DCFH-DA probe.Results: We found that M-PDT induced cSCC apoptosis in a dose-dependent manner, and this result was related to autophagic flux blockage. The phenomenon is confirmed by the results that M-PDT could induce autophagosomes accumulation and upregulate LC3-II and p62 expression. M-PDT elevated co-localization of RFP and GFP tandem-tagged LC3B puncta in cSCC cell, reflecting autophagic flux blockage, and this was confirmed by transmission electron microscopy. Furthermore, we noticed that M-PDT induced accumulated autophagosomes-dependent apoptosis via targeting ROS-mediated Akt/mTOR signaling. Suppression of Akt potentiated M-PDT-induced upregulation of LC3-II and p62 levels, whereas Akt activation and ROS inhibition rendered resistance to these events. In addition, we observed that lysosomal dysfunction was involved in M-PDT-triggered accumulated autophagosomes-dependent cSCC apoptosis.Conclusion: Our data demonstrates that M-PDT inhibits cSCC through blocking Akt/mTOR-mediated autophagic flux.
Sales trends of psychotropic drugs in the COVID-19 pandemic: A national database study in Brazil
Authors: Del Fiol Fernando de Sá , Bergamaschi Cristiane de Cássia , Lopes Luciane Cruz , Silva Marcus Tolentino , Barberato-Filho Silvio 
Published: March 2023

Background: The social restrictions among coronavirus disease 2019 (COVID-19) pandemic have posed a thoughtful risk to mental health and have implications in the use of drugs, including antidepressants, anxiolytics and other psychotropics.Objective: This study analyzed the sales data of the psychotropics prescribed in Brazil, in order to verify the change in consumption trends of these drugs during the COVID-19 pandemic.Methods: This interrupted time-series analyzed psychotropic sales data, between January 2014 and July 2021, using the National System of Controlled Products Management from The Brazilian Health Regulatory Agency. The monthly mean DDDs per 1,000 inhabitants per day of psychotropic drugs was evaluated by analysis of variance (ANOVA) followed by Dunnett Multiple Comparisons Test. The changes in monthly trends in the use of the psychotropic studied were evaluated by Joinpoint regression.Results: During the period studied, clonazepam, alprazolam, zolpidem and escitalopram were the most sold psychotropic drugs in Brazil. According to Joinpoint regression, an upward trend was observed in sales during the pandemic of pregabalin, escitalopram, lithium, desvenlafaxine, citalopram, buproprion and amitriptyline. An increase in psychotropic consumption was noted throughout the pandemic period, with the maximum consumption (2.61 DDDs) occurring in April 2021, with a downward trend in consumption that accompanied the drop in the number of deaths.Conclusions: The increase in sales, mainly of antidepressants during the COVID-19 pandemic, draws attention to issues related to the mental health of the Brazilian population and on the need for greater monitoring in the dispensing of these drugs.
Potent anti-inflammatory responses: Role of hydrogen in IL-1α dominated early phase systemic inflammation
Authors: Wei Youzhen , Wang Kun , Zhang Yafang , Duan Yi , Tian Yan , Yin Hongling , Fu Xuelian , Ma Zuan , Zhou Jianjun , Yu Min , Ni Qingbin , Tang Wenjie 
Published: March 2023

Introduction: It has been proven that hydrogen has obvious anti-inflammatory effects in animal experiments and clinical practice. However, the early dynamic process of the inflammatory response caused by lipopolysaccharide (LPS) and the anti-inflammatory effect of hydrogen has not been definitively reported. Methods: Inflammation in male C57/BL6J mice or RAW264.7 cells was induced with LPS, for which hydrogen was immediately administered until samples were taken. Pathological changes in lung tissue were assessed using hematoxylin and eosin (HE) staining. Levels of inflammatory factors in serum were determined using liquid protein chip. The mRNA levels of chemotactic factors in lung tissues, leukocytes, and peritoneal macrophages were measured by qRT-PCR. The expression levels of IL-1α and HIF-1α were measured by immunocytochemistry. Results: Hydrogen alleviated LPS-induced inflammatory infiltration in the lung tissues of mice. Among the 23 inflammatory factors screened, LPS-induced upregulation of IL-1α etc. was significantly inhibited by hydrogen within 1 hour. The mRNA expression of MCP-1, MIP-1α, G-CSF, and RANTES was inhibited obviously by hydrogen at 0.5 and 1 h in mouse peritoneal macrophages. In addition, hydrogen significantly blocked LPS or H2O2-induced upregulation of HIF-1α, and IL-1α in 0.5 h in RAW264.7 cells. Discussion: The results suggested that hydrogen is potentially inhibitive against inflammation by inhibiting HIF-1α and IL-1α release at early occurrence. The target of the inhibitive LPS-induced-inflammatory action of hydrogen is chemokines in macrophages in the peritoneal cavity. This study provides direct experimental evidence for quickly controlling inflammation with the translational application of a hydrogen-assisted protocol.
Discrimination between human normal renal tissue and renal cell carcinoma by dielectric properties using in-vitro BIA
Authors: Wang Hang , Shi Xuetao , Cao Xinsheng , Dong Xiuzhen , Yang Lin 
Published: March 2023

Renal cell carcinoma (RCC) poses a serious threat to human health, which urgently requires a method that can quickly distinguish between human normal renal tissue (NRT) and RCC for the purpose of accurate detection in clinical practice. The significant difference in cell morphology between NRT and RCC tissue underlies the great potential of the bioelectrical impedance analysis (BIA) to distinguish two types of human tissues. The study aims to achieve such discrimination through comparison of their dielectric properties within the frequency range from 10 Hz to 100 MHz. The dielectric properties of 69 cases of human normal and cancer renal tissue were measured 15 min after tissue isolation in a strictly controlled environment (37°C, 90% humidity). In addition to the impedance parameters (resistivity, conductivity and relative permittivity), the characteristic parameters extracted from the Cole curve were also compared between NRT and RCC. Furthermore, a novel index, distinguishing coefficient (DC), was used to obtain the optimal frequency for discrimination between NRT and RCC. In terms of impedance parameters, the RCC conductivity at low frequencies (&lt;1 kHz) was about 1.4 times as large as that of NRT, and its relative permittivity was also significantly higher (p &lt; 0.05). In terms of characteristic parameters, two characteristic frequencies (14.1 ± 1.1 kHz and 1.16 ± 0.13 MHz) were found for NRT while only one for RCC (0.60 ± 0.05 MHz). A significant difference of low-frequency resistance (R0) between RCC and NRT was also observed (p &lt; 0.05). As for the new index DC, relative permittivity DCs below 100 Hz and at around 14 kHz were both greater than 1. These findings further confirm the feasibility of discrimination between RCC and NRT and also provide data in favor of further clinical study of BIA to detect the surgical margins.