bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA21: Molecular Pathogenesis and Cells of Origin of Intrahepatic Cholangiocarcinoma
Authors: Ilyas Sumera I 
Published: September 2022

Abstract
Intrahepatic cholangiocarcinoma (iCCA) originates in the intrahepatic biliary tree above the second order bile ducts. There are two primary histological subtypes of iCCA: small bile duct iCCAs which arise at the level of the smaller intrahepatic bile ducts, and large bile duct iCCAs which arise in the large intrahepatic bile ducts. Hepatic stem or progenitor cells and cuboidal cholangiocytes are the cells of origin of small bile duct iCCA, whereas large bile duct iCCAs arise from columnar mucous cholangiocytes or peribiliary glands. The molecular pathogenesis of iCCA is distinct from the other anatomic subtypes of CCA. Potentially actionable genomic aberrations that occur in iCCA include fibroblast growth factor receptor 2 (FGFR2) gene fusions, isocitrate dehydrogenase (IDH) 1 and 2 mutations, BRAF mutations, and neutrotrophic tyrosine receptor kinase (NTRK) gene fusions. Epigenetic aberrations that occur in iCCA include inactivating mutations of chromatin remodeling genes such as BAP1 and ARIDIA. Additionally, IDH 1/2 mutations lead to the production of oncometabolites with consequent widespread epigenetic changes. IDH inhibitors and FGFR inhibitors have now received FDA approval for IDH mutated and FGFR altered CCA, respectively. Immune checkpoint inhibition has received tissue agnostic FDA approval for mismatch repair deficient/MSI high CCAs. Other targeted therapies such as PARP inhibitors and CDK4/6 inhibitors are under active investigation.
Citation Format: Sumera I Ilyas. Molecular Pathogenesis and Cells of Origin of Intrahepatic Cholangiocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr IA21.
Abstract IA22: Molecular classes and landscape of drivers of intrahepatic and extrahepatic cholangiocarcinoma
Authors: Sia Daniela 
Published: September 2022

Abstract
Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the neoplastic transformation of the epithelial cells of the bile ducts, both intrahepatic (iCCA) and extrahepatic (eCCA), and among the fastest growing cancers in the United states. Therapeutic options for CCA patients at advanced stages are limited and palliative chemotherapy remains the main treatment option. Over the past decade, the application of next-generation sequencing has significantly impacted the management of CCA where clinically-relevant subgroups have been identified based on the recurrence of specific structural aberrations (i.e. FGFR2 fusions, IDH1 mutations) with important differences according to the anatomical site. These efforts have increased the molecular understanding of this disease and ultimately suggested that iCCA and eCCA may represent distinct entities. Thereby, increasing efforts have tried to generate molecular classifications specific for each subtype, although initial studies analyzed CCA samples regardless of their anatomic site of origin. We will review current knowledge of the molecular landscape and immunogenomic classifications proposed to date for iCCA and eCCA.
Citation Format: Daniela Sia. Molecular classes and landscape of drivers of intrahepatic and extrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr IA22.
Abstract IA26: FGFR2 fusion inhibitors: Clinical benefit and mechanisms of resistance
Authors: Borad Mitesh 
Published: September 2022

Abstract
The fibroblast growth factor pathway (FGFR) has been implicated in a subset of hepatobiliary cancers. Predominant amongst these are fusions/rearrangements for FGFR2 in ~10-15% of intrahepatic cholangiocarcinomas. In this talk we will review: (1) the FGFR pathway and its role in normal physiology, (2) sequencing studies in cholangiocarcinoma with emphasis on discovery of FGFR2 fusions, (3) clinical data for FDA approved FGFR small molecule tyrosine kinase inhibitors, (4) clinical data for second and third generation FGFR inhibitors, (5) determinants of response to therapy for FGFR inhibitors, (6) mechanisms of resistance to FGFR inhibitors and (7) on and off target toxicities for first generation FGFR inhibitors.
Citation Format: Mitesh Borad. FGFR2 fusion inhibitors: Clinical benefit and mechanisms of resistance [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr IA26.
Abstract PO012: In silico drug repurposing identifies mebendazole as a treatment option for chemoresistant hepatoblastoma
Authors: Li Qian , Demir Salih , Bao Xuanwen , Wagner Alexandra , Fan Yanxin , Cairo Stefano , Kappler Roland 
Published: September 2022

Abstract
Resistance to conventional chemotherapy remains a huge challenge in the clinical management and treatment of hepatoblastoma, the most common liver tumor of childhood. The in silico repurposing of drugs with known pharmacokinetics and safety profiles, which have been approved for other indications, represents a promising strategy to identify new drugs effective in chemoresistant hepatoblastoma. In this study, we integrated RNA sequencing-derived gene expression data into the pharmacologic perturbation prediction tool Connectivity Map (CMap) and identified the clinical widely used anthelmintic drug mebendazole as a putative drug to circumvent chemoresistance in hepatoblastoma. Consequently, we experimentally validated the efficacy of mebendazole in permanent and patient-derived xenograft cell lines that are resistant to cisplatin, the therapeutic backbone of hepatoblastoma treatment. Viability assays clearly indicated a potent reduction of tumor cell growth upon mebendazole treatment in a dose-dependent manner. In contrast, similar mebendazole concentrations had little inhibitory effect on the growth of normal neonatal and adult skin fibroblasts. The combination of mebendazole and cisplatin revealed a strong synergistic effect, which was comparable to the one seen with cisplatin and doxorubicin (cardiotoxic), the current standard treatment for high-risk hepatoblastoma patients. Moreover, mebendazole treatment resulted in reduced colony formation capability, induction of apoptosis, and cell cycle arrest of hepatoblastoma cells. Immunofluorescent staining of alpha-tubulin showed that mebendazole causes blockage of microtubule formation and subsequent RNA sequencing analyses confirmed the transcriptional downregulation of tubulins as the major mode of action of mebendazole treatment. Most importantly, mebendazole significantly reduced tumor growth in a subcutaneous xenograft transplantation mouse model. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for doxorubicin in the treatment of chemoresistant hepatoblastoma. This could potentially not only improve outcome but also reduce severe long-term side effects.
Citation Format: Qian Li, Salih Demir, Xuanwen Bao, Alexandra Wagner, Yanxin Fan, Stefano Cairo, Roland Kappler. In silico drug repurposing identifies mebendazole as a treatment option for chemoresistant hepatoblastoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO012.
Abstract PO020: Identification of lipid species: potential biomarkers for early detection of hepatocellular carcinoma
Authors: Leung Kit Yee , Freitas KayLee , Kuang Yu 
Published: September 2022

Abstract
Purpose of Study To investigate alterations in lipid metabolism during carcinogenesis from pretumor tissue towards hepatocellular carcinoma (HCC) and to identify lipid species biomarkers for early detection of HCC. Methods Liver tissue samples were collected from HCC patients. The samples were used to investigate the differences in lipid compositions between tumor and its surrounding hepatic tissue (SHT). A sample of the liver tumor and a sample of SHT were collected from each patient. A total of 32 samples were included in this study. Lipid profiling was performed using an automated electrospray ionization–tandem mass spectrometry with continuous infusion at 30 μl/min. The signal detection limit is 0.0005 mol. Concentrations of 1881 lipid species in tissue samples were analyzed. These lipid species include 348 species in 13 polar lipid groups, 44 species in triacylglycerol (TAG) group and 1489 species containing specific fatty acyl (FA). Lipid species with signal detected above or equal to the detection limit and coefficient of variation below 0.3 were retained for statistical analysis. Concentration differences in lipid species between HCC and SHT were compared using paired t-test or Wilcox signed rank. Differences in lipid compositions between HCC and SHT were assessed. Results Our study shows that significant difference (p &lt; 0.05) of lipid species between SHT and HCC was found in 61 species including 50 species from polar lipid groups and 11 species from TAG group. Most of these species are phosphatidylcholine, ether-linked phosphatidylcholine and TAG species accounted for 36.07%, 13.11% and 18.03% respectively. In addition, significant changes in total ether-linked phosphatidylethanolamine (ePE) and total phosphatidylinositol (PI) were observed. Furthermore, there were significant decreases in FA 18:2 and FA18:3, but significant increase in FA 18:0 in HCC compared with that in SHT. Conclusions Our study suggests that total ePE, total PI, FA 18:0, FA 18:2 and FA 18:3 may serve as biomarkers for the early detection of HCC. Additional study is needed to understand the detailed mechanism of lipid alteration. Our study provides novel insights in the progress of pretumor tissue towards HCC.
Citation Format: Kit Yee Leung, KayLee Freitas, Yu Kuang. Identification of lipid species: potential biomarkers for early detection of hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO020.
Abstract PR03: Pretreatment immune cell composition and checkpoint ligand expression define the response to immunotherapy in advanced HCC: a study using single-cell sequencing
Authors: Cappuyns Sarah , Philips Gino , Vandecaveye Vincent , Verslype Chris , Van Cutsem Eric , Lambrechts Diether , Derkervel Jeroen 
Published: September 2022

Abstract
The novel combination of atezolizumab/bevacizumab has demonstrated unprecedented response rates in a subgroup of advanced hepatocellular carcinoma (aHCC) patients. In order to understand why only a subset of aHCC patients respond to immunotherapy targeting the PD-1/PD-L1 axis, we subjected pre-treatment tissue biopsies from 31 aHCC patients, with mainly non-viral etiologies, to simultaneous single-cell transcriptome (scRNAseq) and T-cell receptor (scTCRseq) sequencing, providing an integrative view of the tumor-microenvironment of aHCC (n=91 169 cells). The therapeutic targets, PD-1 and PD-L1 are expressed in tumor-infiltrating T- cells versus myeloid cells and tumor cells, respectively. Myeloid cells in tumors responding to immunotherapy (according to mRECIST) express significantly higher levels of PD-L1 (p=0.014) compared to non-responders and this is driven by pro-inflammatory PD-L1 expressing CXCL10+ macrophages, involved in T-cell recruitment. In contrast, non-responding tumors are infiltrated by immature CX3CR1+ macrophages and CCR2+ ‘monocyte-like’ macrophages (p=0.009 and p=0.01, respectively). Interestingly, the composition of tumor-infiltrating T-cells did not differ significantly between patient groups. However, responding tumors were characterized by a more clonal baseline T-cell receptor repertoire (p=0.007). Single-cell T-cell receptor sequencing revealed that this clonality was present in activated, effector T-cells, while non-responders had a higher proportion of non-clonal T-cells (p=0.01) concentrated within naïve and memory-like T-cell phenotypes. In conclusion, this is the first and largest aHCC cohort to correlate single-cell sequencing data with clinical outcomes. Prior to treatment, differences in abundancy and ligand expression in small clusters of immune cells as well as difference in baseline T-cell clonality drive response to checkpoint inhibition in aHCC.
Citation Format: Sarah Cappuyns, Gino Philips, Vincent Vandecaveye, Chris Verslype, Eric Van Cutsem, Diether Lambrechts, Jeroen Derkervel. Pretreatment immune cell composition and checkpoint ligand expression define the response to immunotherapy in advanced HCC: a study using single-cell sequencing [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PR03.
Emojilogía: propuesta metodológica para la transformación escolar desde y con el estudiantado
Authors: Yañez-Urbin Cristopher , Figueroa Ignacio , Fica Esteban 
Published: September 2022

(analítico)Este artículo sistematiza una propuesta metodológica denominada emojilogía, la cual se enfoca en el desarrollo de procesos de investigación- acción participativa con y desde el estudiantado. En primer lugar, se aborda la «caja de herramientas» teórico-epistemológica que permite repensar al colectivo estudiantil como agentes sociales válidos para gatillar procesos de transformación escolar. Luego, se profundiza sobre el procedimiento que involucra la propuesta, dando cuenta de la preparación grupal para iniciar el trabajo, la co-construcción de consignas de exploración, la producción de narrativas desde el uso de emojis y la consolidación de espacios de diálogo con el resto de la comunidad educativa. Se concluyen los beneficios y limitaciones de la metodología, vinculados al rol del conflicto como un medio para gatillar transformaciones, pero también como barrera por la generación de resistencias institucionales.
Palabras clave: Educación inclusiva; investigación participativa; cambio social; estudiante.
Medios escolares como procesos significativos en instituciones educativas de Medellín y Montería
Authors: Ceballos-Sepúlveda Juan Carlos , Vélez-Carvajal Julian David 
Published: September 2022

(analítico)El estudio aborda aspectos diferenciadores en la producción de medios escolares que trascienden la visión divulgativa y tradicional de estas experiencias. La indagación se adelantó en instituciones educativas del Valle de Aburrá (Antioquia) y Montería (Córdoba). Desde el punto de vista teórico, se asumen los medios escolares en el campo de la comunicación/educación. La investigación cualitativa se basó en testimonios y reflexiones de estudiantes consultados mediante grupos focales. Los resultados se estructuraron a partir de dos categorías emergentes: temas propios y atribución de sentido. El hallazgo principal indica que los medios escolares se constituyen en un espacio y un proceso que hacen posible la discusión, la deliberación y el establecimiento de acuerdos para la producción, construcción de significados y circulación de contenidos relacionados con el contexto de los estudiantes.
Palabras clave: Medios escolares; medios de comunicación; proceso educativo; comunicación; comunicación y educación.
Two new species of deep water south Brazilian turriforms (Neogastropoda, Conoidea, Turridae and Cochlespiridae)
Authors: Simone Luiz Ricardo Lopes de , Tarasconi José Carlos 
Published: September 2022

Two deep water new species of turriforms are described from south Brazilian coast. One of them is the turrid Polystira tupan sp. nov., one of the largest species of the genus (~80 mm), with proper sculpture, shallow anal notch, collected off Santa Catarina, 350 m. The other is a cochlespirid that has been confused with Cochlespira elegans, a north Atlantic species; as it has different sculpture, shape, peripheric spines, etc., a new species, Cochlespira notomaris sp. nov., is introduced, occurring so far from off Santa Catarina to Rio Grande do Sul, 200‑1,000 m. For comparative purposes, the holotype of C. elegans is also illustrated.
Local farmers’ attitudes towards artificial wildlife bridges in a fragmented agroforestry environment
Authors: Nekaris K.A.I. , Hedger Katherine , Hathaway Amanda , Adinda Esther , Ahmad Nabil , Balestri Michela , Imron Muhammad Ali , Manson Sophie , Nijman Vincent , Campera Marco 
Published: September 2022

Abstract
Fragmentation of tropical forests has severe consequences for global biodiversity. The island of Java, Indonesia has a long history of deforestation and outside the protected area system, the island contains a patchwork of small forest fragments among expanding agricultural land, human settlements, and infrastructure. The arboreal Javan slow loris’ (Nycticebus javanicus) remaining habitat largely occurs in these anthropogenic landscapes. Arboreal canopy bridges have proven to be a successful conservation intervention for Javan slow lorises but must be built on the private land of farmers. Here, we describe the process of collaborating with local farmers to construct and maintain canopy bridges over their farms to aid in connecting habitat for Javan slow lorises. We held non-structured conversations with ten farmers to understand their perceptions of the bridges. We found an overall positive attitude towards slow lorises, as well as acknowledgement of the economic importance of the bridges. Farmers also recommended improvements, including ensuring equity of the bridges in the community and increased financial commitment from the conservation project. There is growing appreciation amongst conservationists that trust and collaboration with local communities are essential for carrying out successful initiatives. We recommend regular discussions with community members in similar interventions to ensure the long-term trust and involvement of local people.
Impact of Reference Mismatch on Procedure Outcomes of Percutaneous Coronary Intervention
Authors: Phan Quang Tan , Nguyen Hieu Lan , Lee Wang Soo , Won Ho Youn , Cho Iksung , Shin Seung Yong , Hong Joon Hwa , Lee Jin Bae , Kim Sang Wook 
Published: September 2022

A significant mismatch between proximal and distal reference lumen diameters of the target lesion may pose challenges during percutaneous coronary intervention (PCI) and therefore influence the outcomes. We investigated total 1706 lesions underwent IVUS guided percutaneous coronary intervention, that were divided into 2 groups, including 411 lesions in Mismatch group and 1295 lesions in Non-Mismatch group. After propensity score matching, 397 lesions in each group were selected for final data set. The analysis showed that Mismatch group PCI required more frequently use of post-stenting optimization (79.6% vs 53.9%, P < .001) using higher max pressure (19.5 ± 3.9 vs 16.7 ± 3.7 atm, P < .001). Besides, Mismatch group also encountered more PCI major complications (7.8% vs 4.0%, P = .024) and lower procedure success rate (91.4% vs 95.5%, P = .022). On final angiogram, Mismatch group had smaller minimum lumen diameter (2.62 ± .45 vs 2.90 ± .57 mm, P < .001) and lower angiographic success rate (93.2% vs 96.7%, P = .023). On final IVUS, Mismatch group had higher rate of incomplete stent apposition and stent edge dissection (6.3% vs 3.0%, P = .029 and 2.5% vs .5%, P = .021, respectively). In conclusion, reference mismatch posed significant challenging during PCI that led to unfavorable procedural outcomes. These impacts may translate into long-term clinical implications that need to be addressed in future studies.
Understanding the Evolution of Environment, Social and Governance Research: Novel Implications From Bibliometric and Network Analysis
Authors: Singh Amit Kumar , Zhang Yifang , Anu  
Published: September 2022

Given the scarcity of comprehensive review studies in the literature, this bibliometric analysis thrives on taking a scientific approach to delivering quantitative and qualitative information on the ever-evolving field of ESG. Utilizing the performance analysis and science mapping techniques which includes citation analysis, co-word analysis, the study reports a holistic overview of 693 (ESG) papers from 1991 to 2020. The paper aims to provide a unified perspective on the evolution and further identify future research directions in this field. The findings point to the most important countries, authors, studies, and top journals in this field. Results show that published articles on ESG gained momentum after 2006; however, an exponential rise is being observed in the past 5 years, with research focusing on sustainable finance, sustainable development, ESG, and CSR with themes extending to risk management, stakeholder engagement, and portfolio construction, among others. Furthermore, the research identifies how the practice of ESG reporting affects many variables such as financial performance, social performance, environmental performance, and sustainability score. The findings also indicate that the field of ESG is still evolving, with numerous unexplored themes. The work is novel and relevant on the pretext that it uses the Scopus and Web of Science databases for bibliometric mapping, whereas previous studies have used the Scopus database but have lacked a robust methodology, so the findings of this study provided strong support for identifying emerging paradigms in the ESG literature.
Assessment of the effects of sodium nitrate (NaNO3) on the reproductive system, liver, pancreas, and kidney of male rats
Authors: SV Rajini , B Chaithra , Basavaiah Shiva 
Published: September 2022

Nitrate (NO3) toxicity is a serious global issue that results in impairment of physiological systems of our body. The present study aimed to investigate the effects of different concentration of NaNO3 (10, 100, 500 and 1000 mg/kg bw) on the male reproductive system, liver, kidney and pancreas. Adult male Wistar rats were divided into five groups of five animals each ( n = 5). The first group served as controls. The second, third, fourth and fifth groups of rat were orally intubated with 10, 100, 500 and 1000 mg/kg bw of NaNO3 for 52 days. After the treatment period, the rats were sacrificed and NO3 induced alterations on selected organs were assessed. There was a dose dependent decrease in sperm motility, serum concentration of testosterone, body weight and organ weight, and increase in abnormal sperm morphology in the NaNO3 treated groups compared with the controls. Further, histological analysis confirmed that NO3 induced toxicity. Shrunken seminiferous tubules and loss of spermatids in testes, shrinkage of acinar cells of the pancreas, sinusoidal congestion and necrosis in the liver, atrophy of glomeruli and congestion of renal tubules of the kidney were the histological alterations observed in rats treated with100 and 500 mg/kg NaNO3. However, 100% mortality was observed in rats treated with 1000 mg/kg NaNO3. The present study clearly demonstrated the toxic effects of NaNO3 on both the reproductive system and other organs of the body. The study might inform human studies; where in the chances of male infertility may be more a problem for individuals in areas with NO3‐rich ground water.