bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

AbstractCities’ 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

AbstractThe 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

AbstractSustaining 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

Abstract
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

Abstract
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

AbstractUnderutilised 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

Abstract
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

AbstractFirms’ 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.