bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of endoscopic nasobiliary cutting in the treatment of hilar cholangiocarcinoma
Authors: Jiang Shujuan , Zhou Zhongyin
Published: June 2023

Objective

The aim of the study was to study the clinical efficacy and prognosis of endoscopically cutting the nasobiliary duct and leaving its residual segment as a biliary stent in the treatment of hilar cholangiocarcinoma (HC).

Methods

The clinical data of 55 patients with HC treated by endoscopic biliary drainage at the Gastrointestinal Endoscopy Center of our hospital (Renmin Hospital of Wuhan University, China) from August 2017 to August 2019 were retrospectively analyzed. According to different drainage schemes, patients were divided into the endoscopic nasobiliary cutting group (n = 26) and the endoscopic retrograde biliary drainage (ERBD) group (n = 29). The postoperative liver function indexes, incidence of postoperative complications, median patency period of stents, and median survival time of patients were compared between the two groups.

Results

Liver function indexes (total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase) were significantly decreased in 55 patients a week postoperaticely (P < 0.05), and decreases in liver function indexes in the endoscopic nasobiliary cutting group were more significant than those in the ERBD group (P < 0.05). The incidence of biliary tract infection in the endoscopic nasobiliary cutting group was significantly lower than that in the ERBD group (15.40% vs. 41.4%, P < 0.05). In the endoscopic nasobiliary cutting subgroups, there were 1 and 3 cases of biliary tract infection in the gastric antrum cutting group (n = 21) and duodenal papilla cutting group (n = 5), respectively, and 0 cases and 2 cases of displacement, respectively; there was a statistically significant difference in terms of complications between the two subgroups (P < 0.05). The median patency period (190 days) and median survival time (230 days) in the nasobiliary duct cutting group were higher than those (169 days and 202 days) in the ERBD group, but there was no significant difference (P > 0.05).

Conclusion

The nasobiliary duct was cut by using endoscopic scissors in Stage II after the bile was fully drained through the nasobiliary duct. The residual segment could still support the bile duct and drain bile. The reduction of jaundice and the recovery of liver enzymes were significant, and the incidence of biliary tract infection was low. Cutting off the nasobiliary duct at the duodenal papilla results in a higher incidence of biliary tract infection, and the residual segment of the nasobiliary duct is more likely to be displaced. Endoscopic nasobiliary-cutting drainage is an effective, simple, and safe method to reduce jaundice in the palliative treatment of HC.
Enhancing the treatment effects of tumor cell purified autogenous heat shock protein 70-peptide complexes on HER-3-overexpressing breast cancer*
Authors: Chen Xia , Zhang Xiaoming , Lu Xiangji , Ren Meng , Su Rina , Gao Weishi , Gao Yanwei
Published: June 2023

Objective

The aim of this study was to enhance the treatment effect of tumor purified autogenous heat shock protein 70-peptide complexes (HSP70-PCs) on HER-3-overexpressing breast cancer.

Methods

In this study, we first studied the expression of HER-3 in breast cancer tissues and its relationship with patient characteristics. We then purified HSP70-PCs from primary breast cancer cells with different HER-2 and HER-3 expression profiles and determined the cytotoxicity of autogenous dendritic cells (DCs) and CD8+ T cells induced by these complexes. Third, recombinant human HSP70-HER-3 protein complexes were used to inhibit the autogenous HSP70-PCs purified from HER-3-overexpressing breast cancer cells, and the resulting immunological response was examined.

Results

The results show that HSP70-PCs can be combined with recombinant HSP70-HER-3 protein complexes to induce stronger immunological responses than autogenous HSP70-PCs alone and that these treatments induce autogenous CD8+ T cell killing of HER-3-positive breast cancer cells.

Conclusion

These findings provide a new direction for HSP70-DC-based immunotherapy for patients with HER-3-overexpressing breast cancer.
Recombinant human vascular endostatin injection to synchronize craniospinal radiotherapy for the treatment of recurrent medulloblastoma in children: A retrospective clinical study*
Authors: Song Yang , Xiao He , Chen Chuan , Liang Ping , Ji Wenyuan , Geng Mingying
Published: June 2023

Objective

Medulloblastoma (MB) is the most common primary central nervous system malignancy in children. Nonetheless, there is no standard treatment for recurrent MB. The purpose of this study was to investigate the clinical value and toxicity of recombinant human endostatin injection (Endostar®) combined with craniospinal radiotherapy for the treatment of recurrent MB in children.

Methods

This study retrospectively analyzed 13 patients with recurrent MB aged 5-18 years. Endostar® 7.5 mg/m2/d was synchronized during craniospinal radiotherapy for 7 children with a portable micro uniform speed infusion pump. Endostar®was applied 3 days prior to the initiation of radiotherapy. The drug was in continuous use for 7 days. Similarly, the withdrawal of the drug took place over 7 days. This represented a cycle. During radiotherapy, the application was repeated until the end of radiotherapy (experimental group). In the other 6 cases, only craniospinal radiotherapy was used (control group).

Results

The complete remission rate was 71.4% in the experimental group and 16.7% in the control group. The median progression-free survival (PFS) was 14 months (95% CI: 0.0-29.60) and 19 months (95% CI: 0.0-39.53) in the experimental and control groups, respectively. The median overall survival (OS) was 19 months (95% CI: 0.0-38.20) and 23 months (95% CI: 2.47-43.53) in the experimental and control groups, respectively. The most common adverse events included grade 1 thrombocytopenia (7.7%), grade 3 neutropenia (38.5%), and grade 1 anemia (30.8%).

Conclusion

Endostar®synchronizing craniospinal radiotherapy significantly improved the complete response rate of children with recurrent MB. It did not increase the side effects of radiation therapy. However, it did not improve the PFS or OS.
A case of sorafenib-induced severe thrombocytopenia during treatment of unresectable hepatocellular carcinoma
Authors: Quan Xiaoying , Chen Xiaoyan , Lei Lei , Wu Chunzhi , Jia Xiaoli , Ye Bin
Published: June 2023

An 81-year-old male with unresectable hepatocellular carcinoma underwent transarterial chemoembolization (TACE) combined with sorafenib. Platelet count was normal before and after TACE treatment, after which oral administration of sorafenib (400 mg po bid) was initiated. During this period, the patient experienced significant diarrhea, so the dosage was reduced to 200 mg po bid. Later, the patient showed obvious gingival bleeding with progressive exacerbation, and his blood routine examination showed a platelet count of 2 × 109 cells/L. The patient was clinically diagnosed with extreme severe thrombocytopenia. The patient was advised to stop taking sorafenib and was immediately treated with hemostasis, platelet transfusion, and suspended red blood cells. After the above treatment, the patient’s symptoms improved, and he was discharged. Up to the date of follow-up, there was no further bleeding.
Relationship between miR-7-5p expression and 125I seed implantation efficacy in pancreatic cancer and functional analysis of target genes*
Authors: Hao Tingting , Wang Chaoqi , Song Yingjie , Wu Wanyan , Li Xuetao , Fan Tao
Published: June 2023

Objective

The aim of this study was to investigate the relationship between miR-7-5p expression and intertissue-125I irradiation sensitivity in pancreatic cancer tissues and to analyze the function of target genes.

Methods

Thirty-seven patients with unresectable pancreatic ductal adenocarcinoma (PDAC) treated with radioactive 125I seed implantation were enrolled. RT-PCR was used to detect the expression level of miR-7-5p in cancer tissues and analyze the relationship between miR-7-5p expression and 125I radiation sensitivity. Bioinformatic software and online tools were used to predict the miR-7-5p target genes and analyze their functional annotation and pathway enrichment.

Results

Radioactive 125I seed implantation was followed up for 2 months. The objective response rate of the miR-7-5p high expression group was 65.0% (13/20), whereas the objective response rate of the miR-7-5p low expression group was 5.88% (1/17), and the difference between the two groups was statistically significant (χ
2 = 13.654, P < 0.001). A total of 187 target genes were predicted using three databases. GO functional annotation showed that target genes were mainly involved in cellular response to insulin stimulus, regulation of gene expression by genetic imprinting, cytosol, peptidyl-serine phosphorylation, bHLH transcription factor binding, cargo loading into vesicles, cellular response to epinephrine stimulus, and nucleoplasm. KEGG pathway enrichment analysis showed that target genes were mainly involved in the ErbB signaling pathway, HIF-1 signaling pathway, axon guidance, longevity regulatory pathway, endocrine resistance, glioma, choline metabolism in cancer, and EGFR tyrosine kinase inhibitor drug resistance. Molecular complex detection analysis by Cytoscape revealed that PIGH, RAF1, EGFR, NXT2, PIK3CD, PIK3R3, ERBB4, TRMT13, and C5orf22 were the key modules of miR-7-5p target gene clustering.

Conclusion

The expression of miR-7-5p in pancreatic cancer tissues positively correlated with the radiosensitivity of 125I seeds. Via targeted gene regulation, miR-7-5p acts on the network of multiple signaling pathways in PDAC and participates in its occurrence and development. Thus, miR-7-5p may become a predictive index of 125I seed implantation therapy sensitivity in PDAC patients.
Recent progress in understanding the role of genes in the pathogenesis of cutaneous squamous cell carcinoma*
Authors: He Yong , Wu Yilin , Zhang Yueyue , Lv Qun , Li Liming , Jiang Mingjun
Published: June 2023

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin tumor in humans. Ultraviolet (UV) radiation is an important environmental risk factor for cSCC; other risk factors include human papilloma virus (HPV) infection, chronic inflammation, and chronic wounds. A large proportion of patients present with an aggressive form of cSCC at the time of diagnosis, which is often accompanied by regional lymph node involvement and distant metastases. The long-term prognosis for these highly metastatic diseases is extremely poor, with a 10-year survival rate of less than 10%. Therefore, clarifying the pathogenesis of this tumor is of great significance and may contribute to the identification of novel biomarkers and development of new therapeutic strategies. In this review, we focus on the recent progress in genes related to the development of this tumor, intending to aid future investigations into the genetic alterations related to cSCC.
Differential gene screening and functional analysis in docetaxel-resistant prostate cancer cell lines*
Authors: Wang Ming , Wang Lei , Zhang Yan , Wang Chaoqi , Li Shuang , Fan Tao
Published: June 2023

Objective

Docetaxel-based combination chemotherapy has traditionally been the standard treatment for metastatic castration-resistant prostate cancer (PCa). However, most patients eventually develop resistance to this treatment, which further reduces their survival. This study aimed to determine key molecular genes in docetaxel-resistant PCa cell lines using bioinformatic approaches.

Methods

The analysis of microarray data GSE33455 (including DU-145/DU-145R and PC-3/PC-3R cell lines) obtained from the Gene Expression Omnibus (GEO) database was performed using GEO2R. Differentially expressed genes (DEGs) of DU-145/DU-145R and PC-3/PC-3R cell lines were selected, and the intersection of DEGs between the two groups was obtained. DEGs were annotated with the Gene Ontology (GO) function and enriched with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway using an online platform (https://cloud.oebiotech.cn/task/detail/array_enrichment/). The online tool Search Tool for the Retrieval of Interacting Genes (https://string-db.org/) was used to obtain the DEG network graph and matrix list, which was imported into Cytoscape 3.6.1 and analyzed using the Molecular Complex Detection plug-in to detect potential functional modules in the network.

Results

A total of 131 intersection DEGs were identified between non-treated and docetaxel-resistant PCa cell lines. GO functional annotation showed that the main genes involved were present in the plasma membrane and were involved in positive regulation of ubiquitin-protein transferase activity, positive regulation of pseudopodium assembly, centriolar subdistal appendage, and heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules. KEGG pathway enrichment analysis revealed that DEGs were mainly involved in IL-17 signaling pathway, cytokine-cytokine receptor interaction, rheumatoid arthritis, legionellosis, and folate biosynthesis. We identified two distinct hubs of DEGs: (1) CD274, C-X-C motif chemokine ligand (CXCL)1, DExD/H-box helicase 58, CXCL2, CXCL8, colony-stimulating factor 2, C-X-C motif chemokine receptor 4 (CXCR4), CXCL5, and CXCL6 and (2) argininosuccinate lyase, argininosuccinate synthase 1, and asparagine synthetase. Except for the CXCR4 gene that was downregulated, the other 11 genes showed upregulated expression.

Conclusion

Certain differential genes may be potential targets for predicting and treating metastatic docetaxel-resistant PCa.
Radiosensitization by microRNA30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft*
Authors: Guo Yuyan , Cui Yingtao , Bao Xing , Ke Yue , Ren Hongtao , Pan Jiyuan , Song Liping , Ma Hongbing
Published: June 2023

Objective

We aimed to observe the radiosensitization effect of mir-30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft and to explore the underlying mechanism.

Methods

A549 cell lines with either stable upregulation or downregulation of mir-30a-5p, and their negative control, were transfected with lentivirus vectors. These cell lines were used to establish a nude mouse model with subcutaneous lung-cancer xenograft. Each group was randomly divided into irradiated and non-irradiated groups. The radiosensitization effect of mir-30a-5p in vivo was studied by observing xenograft growth trends and tumor weight. The mechanisms involved in this radiosensitization were investigated by detecting expressed radiosensitization-related proteins, using immunohistochemistry and Western blotting.

Results

The expression level of mir-30a-5p in the lenti-mir-30a-5p group was higher than that in the negative control (lenti-GFP) group and lower in the lenti-inhibitor group (P < 0.05). Subcutaneous lung-cancer xenografts in the irradiation group and lenti-mir-30a-5p increased in size slowly; tumors were lighter and tumor inhibition rates were higher than those in the non-irradiation and lenti-GFP groups. In contrast, the opposite of these effects was observed in the lenti-inhibitor group. Immunohistochemistry and Western blotting indicated that ATM protein expression level was lower in the lenti-mir-30a-5p group, with or without irradiation, compared to that in the lenti-GFP group. ATM protein levels were higher in the lenti-inhibitor groups. The phosphorylation level of ATM at residue 1981 was low in the groups without irradiation and increased significantly after irradiation (P < 0.05). Moreover, the phosphorylation level was lower in the lenti-mir-30a-5p group and higher in the lenti-inhibitor group than that in the lenti-GFP group after irradiation (P < 0.05).

Conclusion

Mir-30a-5p enhanced the radiosensitivity of nude mice with subcutaneous lung-cancer xenografts by inhibiting ATM phosphorylation.
Nasal-type extranodal NK/T cell lymphoma in association with hemophagocytic syndrome: a case report and literature review*
Authors: Chen Shuang , Huang Yongchu , Cao Yuchun , Zhang Yong
Published: June 2023

We present a rare case of nasal-type CD56-negative NK/T-cell lymphoma. The patient developed hemophagocytic syndrome during diagnosis and treatment. The patient presented to our hospital (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) with “nasal congestion for 3 months and scattered erythema, nodules, and ulcers all over the body for 1 month.” We analyzed clinical manifestations, skin histopathology, immunohistochemistry, and in situ hybridization results. Histopathology of the skin revealed a moderate amount of atypical lymphocyte infiltration between the entire dermis and collagen bundles. Immunohistochemistry showed the following: CD30 (+), TIA-1 (+), CD3(2GV6) (+), CD5 part (+), CD8 part (+), CD43 (+), CD56 (-), CD4 (-), CD20 (-), PAX5 (-), PCK (-), P63 (-), P40 (-), EGFR (-), Ki-67 (the hot spot LI is approximately 80%), and in situ hybridization EBER-ROCH (+). The diagnosis made was “NK/T cell lymphoma nasal type”. This type of lymphoma is aggressive, progresses quickly, and has a poor prognosis. Early clinical manifestations are extremely atypical, especially in the absence of rash. Analysis of the skin manifestations of the disease has a positive effect on its early diagnosis, early treatment, and prognosis.
Research progress on immune checkpoint inhibitors in neoadjuvant therapy for gastric cancer
Authors: Li Wenting , Yu Shiying
Published: June 2023

In recent years, immune checkpoint inhibitors (ICIs) have become an important treatment strategy for advanced gastric cancer. Immunotherapy has gradually transitioned from a later-line to a first-line treatment for advanced gastric cancer. Simultaneously, more and more researchers have begun to pay attention to whether immunotherapy can be used for resectable gastric cancer. The current use of ICIs in the neoadjuvant treatment of gastric cancer is still in its exploratory stage, with a number of clinical trials currently underway. However, the available data show good application prospects. This article reviews the research progress on ICIs in the neoadjuvant therapy for gastric cancer and evokes some unresolved problems.
Analysis of the intestinal flora in patients with primary liver cancer*
Authors: Liu Chengcong , Sun Guoxin , Wang Huizhe , Shang Gaishuang , Yan Xiong , Zou Xiao
Published: June 2023

Objective

To investigate the differences in intestinal flora of patients with primary liver cancer and of healthy individuals and to investigate the effect of the differential flora on the development of liver cancer.

Methods

Overall, 67 patients with primary liver cancer who received systematic and complete treatment between January 2019 and December 2020 at the Sixth People’s Hospital of Qingdao and had complete clinical data were enrolled in this study, and 26 individuals who were healthy on physical examination in the same period were used as healthy controls. Macro genome and 16s ribosome Deoxyribo Nucleic Acid (rDNA) high-throughput sequencing were performed on the stool flora of the enrolled patients and controls, and the differences in the intestinal flora were analyzed using the LEfSe bioinformatics software.

Results

Compared with the control samples, all the tested patient samples showed statistically significant differences in the number of colonies of 5 bacterial phyla, 5 orders, 8 families, 11 genera, and 14 species (P < 0.05).

Conclusion

Compared with healthy people, patients with primary liver cancer have significant differences in the intestinal flora composition. The alteration of the intestinal flora may be correlated with the occurrence of primary liver cancer, and the intestinal flora may become a novel target for the prevention and treatment of primary liver cancer.
Downregulated lncRNA DRAIC enhances the radiotherapy sensitivity of human HCC cell line HepG2 by targeting miR-223-3p
Authors: Li Shuyan , Zhang Jian , Wang Zhengming , Li Wenjun
Published: June 2023

Objective

This study aims to investigate the effects of the long noncoding RNA (lncRNA) DRAIC on the proliferation, apoptosis, and radiosensitivity of hepatocellular carcinoma (HCC) cells and the molecular mechanisms involved.

Methods

Cancer tissues and their corresponding adjacent tissues from 30 patients with HCC were collected, and the expression levels of DRAIC and miR-223-3p were detected via RT-qPCR. DRAIC interference and miR-223-3p overexpression vectors were transfected into HepG2 cells. In addition, DRAIC and miR-223-3p interference vectors were co-transfected into HepG2 cells. The constructed cells were irradiated at 4 Gy. Cell colony formation assay, MTT assay, and flow cytometry were performed to detect the radiosensitivity, proliferation inhibition rate, and apoptosis rate of HepG2 cells, respectively. Dual luciferase reporter gene assay was performed to detect the targeted regulation of DRAIC on miR-223-3p expression.

Results

The expression level of DRAIC in HCC tissues was higher than that in paracancer tissues, whereas the expression level of miR-223-3p was lower in HCC tissues than that in paracancer tissues (P < 0.05). Inhibition of DRAIC expression or overexpression of miR-223-3p increased the proliferation inhibition and apoptosis rates of HepG2 cells (P < 0.05). After irradiation, cell survival fraction decreased and cell proliferation inhibition and apoptosis rates increased (P < 0.05). DRAIC targeted the regulation of miR-223-3p expression, and interference of miR-223-3p expression reversed the effects of inhibiting DRAIC expression on the proliferation, apoptosis, and radiosensitivity of HepG2 cells.

Conclusion

Inhibition of DRAIC expression can inhibit the proliferation of HepG2 cells, promote cell apoptosis, and enhance the radiosensitivity of cells via upregulation of miR-223-3p.
Preliminary security investigation and short-time follow-up of intraoperative intraperitoneal chemotherapy with lobaplatin for advanced colorectal cancer
Authors: Li Qin , Li Xianrong , Feng Libo , Chen Xiaolong , Xia Dong , Xu Linxia
Published: June 2023

Objective

The aim of this study was to conduct a security assessment of intraoperative intraperitoneal chemotherapy using lobaplatin for advanced colorectal cancer.

Methods

From February 2015 to February 2016, 143 patients with colorectal cancer who underwent surgery in our department were selected prospectively. All patients were randomly screened and enrolled into the intraperitoneal chemotherapy (IPC) (74 cases) and control (69 cases) groups, depending on the distribution of cases in the random table. In the trial group, patients were administered 40 mg lobaplatin by intraperitoneal implantation intraoperatively, together with intravenous chemotherapy post-operatively using a typical FOLFOX strategy with oxaliplatin, fluorouracil, and leucovorin. In the control group, only FOLFOX was administered. Bowel function recovery time, adverse reactions and complications, and pre-and post-chemotherapy laboratory examinations were compared. In addition, a 5-year-long follow-up was performed.

Results

Recovery times of bowel function were 73.5 ± 9.7 h and 74.8 ± 10.3 h respectively, and the difference was not significant (P > 0.05). Wound fat liquefaction was observed in five cases in both groups (6.8% vs. 7.2%, P > 0.05). The outcomes of nausea and vomiting (57 cases, 77.0% vs. 50 cases, 72.5%), constipation (43 cases, 58.1% vs. 36 cases, 52.2%), and diarrhea (5 cases, 6.8% vs. 5 cases, 7.2%) were not statistically significant (all P > 0.05). Indices of white blood cell count, blood platelet count, and hepatorenal function were not significantly different (all P>0.05) neither post-operatively nor post-chemotherapy. The 5-year survival rate was not significantly different between the groups (58.1% vs. 56.5%, P > 0.05).

Conclusion

Intraoperative chemotherapy with lobaplatin for advanced colorectal cancer is safe and tolerable.
Treatment-related adverse events of combined anti-angiogenic and immune checkpoint inhibitors: systematic review and meta-analysis
Authors: Chen Lian , Wu Ling , Lu Zhang , Huang Qin , Huang Liu
Published: June 2023

Objective

Immune checkpoint inhibitor (ICI) plus angiogenesis inhibitor (AI) combination therapy is a novel treatment model for multiple cancers that normalizes vascular-immune crosstalk to potentiate cancer immunity. In this review, we summarize the characteristics of adverse effects (AEs) and all fatal cases reported in clinical studies involing ICI + AI therapy.

Methods

Four databases were systematically searched for eligible studies, and 28 relevant studies were selected for inclusion.

Results

Of the patients included, 58.1% developed grade ≥ 3 AEs. The most common fatal AEs were cardiovascular events, severe infections, and hemorrhage. Compared with AI alone, ICI + AI therapy resulted in more cases of grade ≥ 3 proteinuria, liver injury, and fatal AEs (2.49% vs. 1.28%, P = 0.0041), especially respiratory toxicities and severe infections; however, ICI + AI therapy reduced hematological toxicity.

Conclusion

We shared comprehensive and practical safety data to review the adverse events associated with ICI + AI treatment.
Adnexal tumor found during a brain-dead donor organ retrieval: a case report*
Authors: Zhang Bo , Shi Huibo , Xu Jing , Li Xiaoqin , Zeng Mengjun , Tao Ying , Wu Xing , Jiang Jipin
Published: June 2023

Pre-donation evaluation of organ donors is important. Organ quality directly affects both short- and long-term survival rates of transplanted organs and recipients after transplantation. Contraindications to donation are directly related to recipient survival and medical ethics. The following information is included in this organ donation case report: detailed medical history (primary disease and surgical history), blood type, infectious diseases, coagulation function, biochemical function, tumor biomarker, indicators related to tuberculosis infection, microbial culture indicators, lung computed tomography (CT) scan, and abdominal ultrasound (heart, liver, gallbladder, pancreas, spleen, kidneys, ureters, bladder, adnexa). We found a 10 cm × 10 cm space-occupying lesion in the abdominal cavity in this donor organ retrieval surgery. Frozen or paraffin sections showed that the space-occupying lesion was malignant. The organ donor was not suitable due to the malignant tumor, and the transplantation surgery was canceled. We analyzed this case of organ donation to provide a reference for the follow-up donation evaluation process. This case study reveals the limitations of preoperative non-invasive assessment, the necessity of preoperative multi-dimensional assessment of organ function, and the exclusion of donation contraindications.
Successful surgical resection of large hepatocellular carcinoma with portal vein tumor thrombus after conversion therapy with mFOLFOX-HAIC combined with donafenib and sintilimab: two case reports and a literature review*
Authors: Guo Zhitang , Zhang Ming , Liu Ang , Zhang Zhihong , Li Kejia , Ge Jiayun
Published: June 2023

The aim of our study was to evaluate the clinical efficacy of mFOLFOX-HAIC combined with donafenib and sintilimab conversion therapy followed by surgical resection of large hepatocellular carcinoma with portal vein tumor thrombus (PVTT). The clinical data of two patients with large hepatocellular carcinoma who were admitted to the Second Affiliated Hospital of Kunming Medical University were retrospectively collected. Both patients received mFOLFOX-HAIC combined with donafenib and sintilimab conversion therapy, followed by hepatectomy. Clinical data were reported, and clinical efficacy was evaluated. One patient had a 14.5 × 11.1 cm tumor with a tumor thrombus in the right portal vein. The other patient had a 12.1 × 8.3 cm tumor with portal and hepatic vein tumor thrombi. Both patients had CNLC stage IIIa prior to conversion therapy, which was reduced to stage Ib after conversion therapy. Subsequently, the patient underwent open and laparoscopic right hemihepatectomies. Short-term high-intensity conversion therapy with mFOLFOX-HAIC combined with donafenib and sintilimab is a feasible and effective treatment for patients with large hepatocellular carcinoma with PVTT.
Constructing smarter and more sustainable urban ecosystems: a dynamic analysis of challenges and initiatives
Authors: Rodrigues Maria I. R. P. R. , Ferreira Fernando A. F. , Ferreira Neuza C. M. Q. F.
Published: June 2023

Cities’ weaknesses have been revealed by their struggle to respond to current challenges (e.g., pandemic crises and population and urbanization exponential growth). Urban planners are thus increasingly concerned about implementing initiatives in their metropolises that favor a better present and future quality of life. In this context, cities need to become enablers of economic and social development and increased prosperity through the integration of technologies into projects promoting smarter and more sustainable urban ecosystems. These ecosystems are, however, highly complex due to their specificities and multifaceted nature, which makes analyzing them a difficult endeavor. Based on a constructivist and complementarity logic, this study sought to develop a multicriteria analysis model to support relevant decision-making processes in this study context. A panel of experts was recruited to create the analysis system using a combination of cognitive mapping and the decision-making trial and evaluation laboratory technique in an neutrosophic context. This approach overcomes various flaws identified in previous related research. The entire procedure focused on enhancing the experts’ learning through participation not only to structure the problem under analysis but also to identify and prioritize the factors and/or determinants of smartness and urban sustainability. The model provides a holistic, solid, and clear vision of the decision problem that fosters appropriate choices when creating and evaluating smart, sustainable urban ecosystems.
Ordoliberalism goes China? A comparison of recent developments in EU and chinese competition law considering the digital economy
Authors: Küsters Anselm
Published: June 2023

The rapidly advancing digitalisation of the global economy, particularly the emergence of quasi-monopolists with the ability to define the rules of the game, poses numerous challenges to competition law as it is now practised worldwide. The European Union and China, in particular, have recently taken up these challenges with far-reaching reforms of their respective competition law regimes. This paper analyses these reforms and trends from a critical perspective informed by ordoliberalism, one of the arguably most influential schools of competition thought. First, the core ideas of the early Freiburg School on competition are distilled. The subsequent sections compare this ideal type with current developments in EU and Chinese competition law. The discussion of similarities and differences shows that both reform agendas suffer from similar problems connected to the rule of law and suggests that a modernised ordoliberal competition law approach must be guided not only by substantive but also by procedural aspects.
Modelling the sustainability of a primary school digital education curricular reform and professional development program
Authors: El-Hamamsy Laila , Monnier Emilie-Charlotte , Avry Sunny , Chevalier Morgane , Bruno Barbara , Dehler Zufferey Jessica , Mondada Francesco
Published: June 2023

Sustaining changes in teachers’ practices is a challenge that determines the success of curricular reforms, from which Digital Education (DE) is not exempt. As the literature on sustainability is considered “scarce” and “scattered”, long-term studies modelling the factors impacting teachers’ sustained uptake of DE pedagogical content are lacking. Thus, we investigate whether and how 287 in-service teachers sustained a primary school DE curricular reform over a year after they completed their two-year DE professional development program. We model the sustainability of the reform through Structural Equation Modelling, and identify critical sustainability-factors. The validated Sustainable Adoption of Digital Education (SADE) model confirms that sustainability in the fourth year of the reform depends on perceived usefulness of teaching the new content, ease of implementation, and access to sufficient support in schools. Such factors should thus be evaluated, accounted for in the implementation phase of the reform, and sustained over time. The findings confirm that the DE curricular reform model contributes to positive self-efficacy to teach DE, provides sufficient in-school support, and promotes increasing adoption over time. However, as teachers’ practices have not yet stabilised, and teachers may still adopt more to cover the breadth of DE-concepts, it is important to remain attentive to remaining sustainability barriers: lack of time, effort required to teach DE with teachers preferring to delegate, and lack of student-learning evidence, the latter being a significant challenge to address in the literature. These barriers must therefore be jointly addressed by researchers and practitioners in the field in order to promote the sustainability of the reform.
Target trial emulation of aspirin after diagnosis of colorectal polyps
Authors: Emilsson Louise , Song Mingyang , Ludvigsson Jonas F.
Published: June 2023

Backgound and Aims

Previous research on the potential chemoprotective effect of aspirin for colorectal cancer (CRC) shows conflicting results. We aimed to emulate a trial of aspirin intiation in individuals with incident polyps.

Methods

We identified individuals registered with their first colorectal polyp in the nationwide gastrointestinal ESPRESSO histopathology cohort in Sweden. Individuals aged 45–79 years diagnosed with colorectal polyps 2006–2016 in Sweden without CRC or contraindications for preventive aspirin (cerebrovascular disease, heart failure, aortic aneurysms, pulmonary emboli, myocardial infarction, gastric ulcer, dementia, liver cirrhosis, or any other metastatic cancer) registered until the month of first polyp detection were eligible. Using duplication and inverse probability weighting, we emulated a target trial of aspirin initiation within 2 years of initial polyp detection. The main outcome measures were incident CRC, CRC mortality and all-cause mortality registered until 2019.

Results

Of 31,633 individuals meeting our inclusion criteria, 1716 (5%) initiated aspirin within 2 years of colon polyp diagnosis. Median follow-up was 8.07 years. The 10-year cumulative incidence in initiators versus non-initiators was 6% versus 8% for CRC incidence, 1% versus 1% for CRC mortality and 21% versus 18% for all-cause mortality. The corresponding hazard ratios were 0.88 (95% confidence interval, 95%CI = 0.86–0.90), 0.90 (95%CI = 0.75–1.06) and 1.18 (95%CI = 1.12–1.24).

Conclusion

Aspirin initiation in individuals with polyp removal was linked to 2% lower cumulative incidence of CRC after 10 years but did not alter CRC mortality. We also observed a 4% increased risk difference of all-cause mortality at 10 years after the initiation of aspirin.
Refactoring with domain-driven design in an industrial context
Authors: Özkan Ozan , Babur Önder , van den Brand Mark
Published: June 2023

Context

Software developers need to constantly work on evolving the structure and the stability of the code due to changing business needs of the product. There are various refactoring approaches in industry which promise improvements over source code composition and maintainability.

Objective

In our research, we want to improve the maintainability of an existing system through refactoring using Domain-Driven Design (DDD) as a software design approach. We also aim for providing empirical evidence on its effect on maintainability and the challenges as perceived by developers.

Method

In this study, we applied the action research methodology, which facilitates close academia-industry collaboration and regular presence in the studied product. We utilized focus groups to discover problems of the existing system with a qualitative approach. We reviewed the subject codebase to construct our own expert opinion as well and identified problems in the codebase and matched them with the ones raised by engineers in the team. We refactored the existing software system according to DDD principles. To measure the effects of our actions, we utilized Technology Acceptance Model (mTAM) questionnaire, and also semi-structured interviews with the development team for data collection, and card sorting methodology for qualitative analysis. For minimizing bias that might affect our results with the existing software engineers in the team, we extended our measurement with three new joiner software engineers in the team through the think aloud protocol.

Results

We have identified that engineers mostly gave positive answers to our interview questions, which are mapped to software maintainability metrics defined by ISO/IEC 25010. Our DDD refactoring scored 85 in PU and 83 in PEU, leading to an overall mTAM score of 84. This means acceptable on the acceptability scale, B on the grade scale, and good on the adjective rating scale.

Conclusion

Our research led us to conclude that a powerful design approach, like DDD, is an effective tool for restructuring and resolving software issues in this situation. It offers standardization to the software and the refactoring efforts. We realized that DDD entails a certain degree of complexity and cognitive load, which is a barrier for software engineers, but they are aware of its benefits.
Genome resources for underutilised legume crops: genome sizes, genome skimming and marker development
Authors: Diakostefani Antonia , Velissaris Rania , Cvijanovic Emilia , Bulgin Robin , Pantelides Andriana , Leitch Ilia J. , Mian Sahr , Morton Joseph A. , Gomez Marybel Soto , Chapman Mark A.
Published: June 2023

Underutilised crops suffer from under-investigation relative to more mainstream crops, but often possess improved stress tolerance and/or nutrition, making them potentially important for breeding programmes in the context of climate change and an expanding human population. Developing basic genome resources for underutilised crops may therefore catalyse analyses to facilitate their use, through improved understanding of population structure, phylogeny, candidate genes, and linkage mapping. We carried out nuclear and plastid genome sequencing and assembly for five underutilised legumes: jack bean, sword bean, Kersting’s groundnut, moth bean, and zombi pea. Using only ‘off-the-shelf’, free-to-use bioinformatic tools, we also developed a simple but effective pipeline to identify thousands of markers, which could be applied in other species. We assembled 53–68% of the genome and 73–95% of the gene space in the five legumes. The assemblies were fragmented but nevertheless useful for identifying between 34,000—60,000 microsatellites. Examination of 32 markers in zombi pea revealed 16 primer pairs which amplified in at least half of the eight accessions tested and were polymorphic. We also present nuclear genome size estimates for 17 legume taxa (12 for the first time), comprising the above five species as well as other domesticated legume species and crop wild relatives. We aim for the newly developed markers and genome size estimates presented here to be useful for the research community by aiding genomic and population genetic studies for these taxa, and to provide information on approaches that can be applied for investigating other important yet underutilised crops.
Comparative analysis of tear cytokines in patients with glaucoma, ocular hypertension, and healthy controls
Authors: Mravec Bencurova Dominika , Vyborny Petr , Dankova Pavlina
Published: June 2023

Purpose

To investigate the ocular surface inflammation in patients with primary open angle glaucoma and ocular hypertension by analyzing tears and to compare findings with healthy controls.

Methods

Observational case–control study. Tear samples were collected by 5 µl microcapillary tube from 24 patients with glaucoma treated by antiglaucoma drops, 9 non-treated patients with ocular hypertension and 45 healthy controls. Tears were analyzed from right eye by multiplex Bio-Plex system for the presence of 6 cytokines: IL1β, IL10, IL4, IFNγ, MIF and VEGF.

Results

Significantly higher concentrations of IL1β and IL10 (glaucoma or ocular hypertension vs. healthy controls, p < 0.0001), VEGF (glaucoma vs. ocular hypertension, p < 0.05; ocular hypertension vs. healthy controls, p < 0.02) and MIF (glaucoma vs. healthy controls, p < 0.03) were detected in patients’ tears. Both patient groups have activated to a significantly lower extent the Th1 pathway represented by IFNγ than Th2 pathway represented by IL10 (p < 0.001) and, at the same time, the IFNγ/IL4 ratio was significantly increased in healthy controls (p < 0.001) and patients with ocular hypertension (p < 0.02) compared to glaucoma individuals.

Conclusion

This study shows that secretion of inflammation-related cytokines by conjunctival cells is increased in both, glaucoma and ocular hypertension patients and can be detected in their tears. Nevertheless, data indicates stronger ocular surface inflammation in non-treated follow-up patients diagnosed with ocular hypertension than in glaucoma subjects treated by antiglaucoma drops.
Configurations of business model themes and strategies in small firms: a qualitative comparative analysis
Authors: Campagnolo Diego , Gianecchini Martina , Mosca Luigi
Published: June 2023

Firms’ strategies and business model themes (BMTs) entail choices that create a configuration of interdependent elements that ultimately affect a firm’s performance. So far, extant studies on BMTs (i.e. novelty, efficiency, complementarity and lock-in) have neglected an explorative analysis of how configurations of BMTs and the choices of a firm’s strategy (namely, the source of the competitive advantage and the market scope) are associated with a firm’s performance in small and medium enterprises (SMEs). We address this limitation by analysing a sample of 96 small firms using a configurational approach. We identified four equifinal configurations leading to high performance and five equifinal configurations associated with low performance. Overall, our results suggest that in small firms, it is essential to combine a differentiation strategy with either consistent pairs of BMTs or the search for new avenues of value creation and capture, while featuring too many BMTs might be detrimental to their growth. Our study contributes to the scholarly debate about the relationship between business models and strategy.
Strategies for transnational projection through international book fairs
Authors: Villarino Pardo M. Carmen
Published: June 2023

The following article aims to analyze the projection and representation of literary systems in some of the main international book fairs (IBF) at present, based on theoretical-methodological proposals from the Sociology of Literature and Culture (Bourdieu in ARSS 145, 3–8, 2002; Sapiro Translatio. Le marché de la traduction en France à l’heure de la mondialisation, CNRS Éditions, 2008; Even-Zohar, Polisistemas de Cultura. Laboratorio de investigación de la cultura, 2017). We begin with the hypothesis of considering IBFs as places for the acquisition of capital (literary, cultural, economic and symbolic) and for negotiating struggles for positions of greater or lesser centrality in the transnational literary field and in the world publishing market, and in terms of the image of countries, cultures, or cities. In those IBFs offering the position of Guest of Honor, this becomes a privileged opportunity—for governments, institutions and different actors involved in the book chain—for the international projection of the image of a country, culture, city or literary system. Different strategies for cultural and literary promotion in this worldwide scenario of symbolic goods will be discussed, with special attention to the case of Brazil (contrasted, partly, with that of Spain).
Non-Oxidative Ethane Dehydrogenation in a Packed-Bed DBD Plasma Reactor
Authors: Cameli Fabio , Dimitrakellis Panagiotis , Stefanidis Georgios D. , Vlachos Dionisios G.
Published: June 2023

Plasma-assisted conversion of ethane (C2H6) can produce value-added chemical building blocks using green electricity. Here we employ a simple packed-bed coaxial dielectric barrier discharge (DBD) reactor to convert C2H6 at mild operating conditions unattainable by conventional thermocatalysis. Ethylene (C2H4), acetylene (C2H2), and methane (CH4) are the main products along with small fractions of C3 and C4 hydrocarbons. Interestingly, the C2H4 selectivity is primarily correlated to C2H6 conversion, dominated by electron dissociation and recombination reactions irrespective of the dielectric properties of the packed bed material (SiO2, Al2O3, ZrO2, TiO2, and BaTiO3), packing material size, supplied power, and C2H6 concentration. While a distortion of the electric field and discharge propagation results in varying dissipated power as materials change, the C2H4 energy yield remains constant. The particle size appears to affect conversion mainly due to pressure alterations. Pd/SiO2 catalyst can change the selectivity, favoring saturated species by expending hydrogen.
Diurnal water fluxes and growth patterns in potato tubers under drought stress
Authors: Huntenburg Katharina , Pflugfelder Daniel , Koller Robert , Dodd Ian Charles , van Dusschoten Dagmar
Published: June 2023

Background and aims

Potato tubers comprise 83% water at harvest, but surprisingly few studies address tuber water relations in drying soil. This study aims to understand whether soil drying alters tuber water fluxes and their effect on tuber volume growth.

Methods

Tuber water content and volume growth were investigated every 4 h using magnetic resonance imaging (MRI) during soil drying and re-watering, with leaf gas exchange, leaf water potential and foliar abscisic acid (ABA) concentration measured concurrently.

Results

Tubers of well-watered plants showed a diurnal growth pattern with their volume and average water content (TWC) increasing overnight. Withholding irrigation caused typical shoot drought stress responses (e.g. stomatal closure), dampened fluctuations in total TWC and paused nocturnal volume growth. Irrespective of soil moisture, tubers lost water (likely to the shoot) during the daytime when the plant transpires, while tuber water loss to the soil was minimal. Re-watering restored tuber volume growth and average TWC due to root water uptake and transport to the tuber.

Conclusions

Potato tubers can supply water to the shoot. Nocturnal water influx needs to exceed daytime water efflux for net tuber volume growth, which should be considered in irrigation management.