bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P48: Advancing Personalized Anti-Cancer Pharmacotherapy: Magnetic Bioprinting of a Ductal Drug Screening Platform for Salivary Gland Mucoepidermoid Carcinoma
Authors: Oo Yamin , Truong Tien T.T. , Phan Toan V. , Ahmed Khurshid , Rodboon Teerapat , Chaisuparat Risa , Souza Glauco R. , Ferreira Joao N. 
Published: April 2024

Abstract
Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the salivary glands (SG), and it arises from “reserve” stem cells within the ductal network. Recently, our research team has consistently generated acinar-like epithelial SG organoids using a magnetic three-dimensional bioprinting (M3DB) platform. However, 3D ductal constructs with lumenized and functional features have not been established by biofabrication strategies due to challenges related to the lack of epithelial polarity and reproducibility. Consequently, our research unit is developing an in vitro high throughput drug screening platform with bio-printed ductal constructs as avatars of MEC ductal units towards a more effective and personalized anti-cancer pharmacotherapy. M3DB, multiplex immunofluorescence, western blot, and functional assays were performed. M3DB induced the formation of ring-like organoid 3D constructs after the magnetic bioassembly of MEC HTB41 cells overnight. These bio-printed constructs had a lumen formation efficiency of ~70% and contained functional E-cadherin+ cell clusters expressing ZO-1 with mainly K14+ and K5+ ductal progenitor populations with high pro-mitotic activity (Ki-67). These bio-printed ductal-like constructs were then proteomic and functionally evaluated in the presence or absence of 5-fluorouracil (5-FU), a chemotherapy drug. Proteomic assessments revealed changes in cellular antioxidant response (Nrf2) as well as DNA damage repair (γ-H2AX) after 5-FU exposure, potentially safeguarding cells from damage and halting cancer cell cycle progression. Tumor cell invasion capabilities within co-culture in mili-fluidic platforms, and functional evaluation with cholinergic and adrenergic agonists and swelling assays confirmed the 5-FU-induced cytotoxicity, decreased invasion potential, and ductal hypofunction. In summary, our team successfully established novel bio-printed MEC ductal-like avatar platforms that will pave the way for personalized pharmacotherapy and precision oncology in SG malignant tumors.
Citation Format: Yamin Oo, Tien T.T. Truong, Toan V. Phan, Khurshid Ahmed, Teerapat Rodboon, Risa Chaisuparat, Glauco R. Souza, Joao N. Ferreira. Advancing Personalized Anti-Cancer Pharmacotherapy: Magnetic Bioprinting of a Ductal Drug Screening Platform for Salivary Gland Mucoepidermoid Carcinoma [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P48.
Abstract P52: Combination of 5-fluorouracil and Menadione Exerts Synergistic Effect on Colorectal Cancer Cells by Targeting Wnt/β-catenin Signaling Pathway
Authors: Warrier Vidya P , Venkatachalam Sankaran , Ramasamy Sakthivel , Gromiha M Michael , Karunagaran Devarajan 
Published: April 2024

Abstract
Colorectal cancer is the third most common type of cancer and the second most in terms of mortality rate worldwide. 5-fluorouracil (5-FU), the fluoropyrimidine drug, that interferes with DNA replication and repair processes, is the first-line-of-treatment against colorectal cancer. However, cells gain resistance over time and relapses occur upon continuous 5-FU therapy. Interestingly, 5-FU promotes stemness in colorectal cancer via Wnt signaling pathway which is critical for its progression. Studies have pointed out the possibility of using a Wnt signaling inhibitor along with 5-FU as a better strategy to overcome the poor outcomes of current 5-FU based therapies. We have previously shown that menadione (vitamin K3) suppresses Wnt signaling pathway in colorectal cancer cells. In the present study, we attempted to evaluate if the combination of menadione and 5-FU can exert a synergistic effect in the human colorectal cancer cell lines HCT116 and SW620. Analysis of the cell viability assay results using CompuSyn software confirmed that the combination indeed acts synergistically. The combination efficiently downregulated the expression of the Wnt signal transducer protein, β-catenin, and the expression of other proteins in the pathway such as phospho-GSK3β in the cell lines HCT116 and SW620. Docking of the individual drugs and their combination on β-catenin using Autodock Vina showed that 5-FU and menadione in combination bind to key protein-protein interaction (PPI) sites of β-catenin whereby they may inhibit β-catenin-TCF interaction or activate the β-catenin destruction complex. Taken together, our data possibly explains that the synergistic action of 5-FU and menadione in colorectal cancer cells may be due to the simultaneous binding of the two drugs to multiple PPI sites thereby blocking the activity of β-catenin.
Citation Format: Vidya P Warrier, Sankaran Venkatachalam, Sakthivel Ramasamy, M Michael Gromiha, Devarajan Karunagaran. Combination of 5-fluorouracil and Menadione Exerts Synergistic Effect on Colorectal Cancer Cells by Targeting Wnt/β-catenin Signaling Pathway [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P52.
Abstract P57: A Transcriptome-Wide Meta-Analysis Reveals Lack Of Cancer-Cell Intrinsic Determinants Of Response To Immune Checkpoint Blockade
Authors: Guo Yu Amanda , Kulshrestha Tanmay , Chang Mei Mei , Kassam Irfahan , Revkov Egor , Rizzetto Simone , Tan Aaron C. , Tan Daniel S.W. , Tan Iain Beehuat , Skanderup Anders Jacobsen 
Published: April 2024

Abstract
Immune-checkpoint blockade therapy (ICB) has conferred significant and durable clinical benefit to some cancer patients. However, most patients do not respond to ICB, and reliable biomarkers of ICB response are needed to improve patient stratification. Current FDA-approved biomarkers for ICB include PD-L1 expression, microsatellite instability (MSI), and high tumor mutation burden (TMB) of &gt;10mutations/Mb. In addition, gene expression signatures of tumor immune phenotypes have been proposed to predict for ICB response. Despite these efforts, there is a lack of large-scale transcriptome-wide studies to identify and characterize potential biomarkers of ICB response conserved across cancer types in a cell type specific manner. Here, we performed a transcriptome-wide meta-analysis across 1,486 tumors from ICB-treated patients and tumors with expected ICB outcomes based on microsatellite status. Using a robust transcriptome deconvolution approach, we inferred cancer and stroma-specific gene expression differences and identified cell-type specific features of ICB response across cancer types. We identified 59 stroma-specific differentially expressed genes associated with ICB-response, which were strongly enriched in immune-related pathways and processes. Stromal expression of CXCL9, CXCL13, IFNG, and CD274 were among the top positive determinants of ICB response, consistent with current knowledge. Interestingly, we also identified a group of potential immune-suppressive genes, including FCER1A, associated with poor response to ICB. Surprisingly, the unbiased transcriptome-wide analysis failed to identify cancer-cell intrinsic features of ICB response conserved across tumor types. Overall, our results suggest that cancer cells lack tissue-agnostic molecular determinants of ICB response, which has implications for the development of improved ICB diagnostics and treatments.
Citation Format: Yu Amanda Guo, Tanmay Kulshrestha, Mei Mei Chang, Irfahan Kassam, Egor Revkov, Simone Rizzetto, Aaron C. Tan, Daniel S.W. Tan, Iain Beehuat Tan, Anders Jacobsen Skanderup. A Transcriptome-Wide Meta-Analysis Reveals Lack Of Cancer-Cell Intrinsic Determinants Of Response To Immune Checkpoint Blockade [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P57.
Abstract P64: Adipose-enriched Peri-tumoral Stroma Prognosticates Poorer Survival in Breast Cancers
Authors: Lau Hannah Si Hui , Tan Veronique Kiak Mien , Tan Benita Kiat Tee , Sim Yirong , Quist Jelmar , Thike Aye Aye , Tan Puay Hoon , Pervaiz Shazib , Grigoriadis Anita , Sabapathy Kanaga 
Published: April 2024

Abstract
Background: Breast cancers display a large degree of diversity between and within tumors. Intra-tumoral heterogeneity is contributed by variations in tumor cells and non-malignant stromal and immune cells of the tumor microenvironment (TME). So far, studies on the TME have focused on intra-tumoral stroma, whereas little attention has been given to the peri-tumoral microenvironment, extending beyond the tumor margins into the surrounding histologically normal-appearing tissues. Here, we hypothesized that intrinsic intra-tumoral heterogeneity impacts the more distal peri-tumoral stroma, which may in turn affect tumor growth and development.
Methods: A systematic, multi-regional transcriptomic profiling analysis of the tumor and peri-tumoral regions from 8 ER+/PR+/HER2− invasive breast carcinomas was performed using the human Clariom™ S Assay. For each patient, 5 spatially distinct tumor samples were obtained, while peri-tumoral samples were collected from 4 different sides and at varying distances up to 7 cm from tumor margins. Pathway enrichment analyses and cellular deconvolution were performed to determine their molecular characteristics and cell type compositions. Gene expression signatures identified from peri-tumoral samples were applied to tumor-adjacent normal RNA-seq samples from 50 TCGA ER+/PR+/HER2− breast cancer patients to determine their prognostic value.
Results: The 8 tumors displayed varying levels of spatial diversity in their biological properties, including 3 tumors with basal-classified regions. Four peri-tumoral clusters with distinct pathway activities and cell compositions were identified, but were independent of distance and location to the tumor. Two clusters reflect the major breast peri-tumoral states – a pro-inflammatory, adipose-enriched phenotype which was significantly associated with poorer overall survival (HR=4.28, p-value=0.02), and an adaptive immune cell- and myofibroblast-enriched phenotype.
Conclusion: This suggests that the peri-tumoral stroma may be an important determinant in cancer progression. Moreover, independent of spatially-defined patterns, the peri-tumoral phenotype appears to be driven by inter-individual variations in the proportion of fibroglandular and fat tissue of the breast.
Citation Format: Hannah Si Hui Lau, Veronique Kiak Mien Tan, Benita Kiat Tee Tan, Yirong Sim, Jelmar Quist, Aye Aye Thike, Puay Hoon Tan, Shazib Pervaiz, Anita Grigoriadis, Kanaga Sabapathy. Adipose-enriched Peri-tumoral Stroma Prognosticates Poorer Survival in Breast Cancers [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P64.
Exploring an EM-algorithm for banded regression in computational neuroscience
Authors: Fuglsang Søren A. , Madsen Kristoffer H. , Puonti Oula , Siebner Hartwig R. , Hjortkjær Jens 
Published: April 2024

Abstract
Regression is a principal tool for relating brain responses to stimuli or tasks in computational neuroscience. This often involves fitting linear models with predictors that can be divided into groups, such as distinct stimulus feature subsets in encoding models or features of different neural response channels in decoding models. When fitting such models, it can be relevant to allow differential shrinkage of the different groups of regression weights. Here, we explore a framework that allows for straightforward definition and estimation of such models. We present an expectation-maximization algorithm for tuning hyperparameters that control shrinkage of groups of weights. We highlight properties, limitations, and potential use-cases of the model using simulated data. Next, we explore the model in the context of a BOLD fMRI encoding analysis and an EEG decoding analysis. Finally, we discuss cases where the model can be useful and scenarios where regularization procedures complicate model interpretation.
Understanding stunting risk factors in Kampar Regency: Insights from mothers with stunted children (qualitative study)
Authors: Suyanto Suyanto , Wahyuni Sri , Zulharman Zulharman , Restila Ridha , Irfansya Raffhy , Aprillianty Erfa Natasya , Adraf Natasha Widya 
Published: April 2024

Objective: To assess the perceptions of mothers with stunted children regarding the factors contributing to stunting in Kampar Regency, Riau Province, Indonesia. Introduction: Stunting is intricately linked to underlying risk factors, and understanding these factors is crucial for preventing its recurrence, particularly for mothers who play a central role in caring for stunted children. Methods: The research sample consisted of mothers referred by the Perhentian Raja Community Health Center with stunted children. Purposive sampling was employed to select informants and thematic analysis was used for data analysis. Results: A total of 15 informants were interviewed, leading to the identification of five themes related to stunting risks: (1) before pregnancy, (2) during pregnancy, (3) postnatal, (4) infectious disease factors, and (5) socio-demographic factors. Conclusion: The study indicates that mothers hold diverse opinions about factors contributing to stunting, with their views being shaped by health programs and personal experiences, specifically focusing on aspects like breastfeeding and weaning foods. Additionally, it underscores that education and economic challenges introduce complexity to understanding how mothers perceive the risk factors associated with stunting.
From symptom onset to ED departure: understanding the acute care chain for patients with undifferentiated complaints: a prospective observational study
Authors: Claassen Lieke , Ritter Laura Magdalena , Latten Gideon Hubertus Petrus , Zelis Noortje , Cals Jochen Willo Lennert , Stassen Patricia Maria 
Published: April 2024

Abstract
Background
For most acute conditions, the phase prior to emergency department (ED) arrival is largely unexplored. However, this prehospital phase has proven an important part of the acute care chain (ACC) for specific time-sensitive conditions, such as stroke and myocardial infarction. For patients with undifferentiated complaints, exploration of the prehospital phase of the ACC may also offer a window of opportunity for improvement of care. This study aims to explore the ACC of ED patients with undifferentiated complaints, with specific emphasis on time in ACC and patient experience.

Methods
This Dutch prospective observational study, included all adult (≥ 18 years) ED patients with undifferentiated complaints over a 4-week period. We investigated the patients’ journey through the ACC, focusing on time in ACC and patient experience. Additionally, a multivariable linear regression analysis was employed to identify factors independently associated with time in ACC.

Results
Among the 286 ED patients with undifferentiated complaints, the median symptom duration prior to ED visit was 6 days (IQR 2–10), during which 58.6% of patients had contact with a healthcare provider before referral. General Practitioners (GPs) referred 80.4% of the patients, with the predominant patient journey (51.7%) involving GP referral followed by self-transportation to the ED. The median time in ACC was 5.5 (IQR 4.0-8.4) hours of which 40% was spent before the ED visit. GP referral and referral to pulmonology were associated with a longer time in ACC, while referral during evenings was associated with a shorter time in ACC. Patients scored both quality and duration of the provided care an 8/10.

Conclusion
Dutch ED patients with undifferentiated complaints consulted a healthcare provider in over half of the cases before their ED visit. The median time in ACC is 5.5 h of which 40% is spent in the prehospital phase. Those referred by a GP and to pulmonology had a longer, and those in the evening a shorter time in ACC. The acute care journey starts hours before patients arrive at the ED and 6 days of complaints precede this journey. This timeframe could serve as a window of opportunity to optimise care.
The prevalence of accessory renal arteries in sudanese population in Khartoum State: a cross-sectional CT study from 2017 to 2020
Authors: Mohammed Safaa. , AbdAlla Eltayeb. , Elhag Amal. , El-Mardi Abdelmoniem. 
Published: April 2024

Abstract
Background
Renal artery variations are clinically significant due to their implications for surgical procedures and renal function. However, data on these variations in Sudanese populations are limited. This study aimed to determine the prevalence and characteristics of renal artery variations in a Sudanese population.

Methods
A cross-sectional retrospective study was conducted in Khartoum state from October 2017 to October 2020. A total of 400 Sudanese participants who underwent abdominal CT scans were included. Data on demographic characteristics, kidney measurements, and renal vasculature were collected and analyzed using descriptive statistics and inferential tests.

Results
The mean age of participants was 46.7 ± 18 years, with a nearly equal gender distribution. Overall, renal artery variations were present in 11% of participants, with accessory renal arteries observed in 6% of the study population. Among those with accessory vessels, 50% were on the right side, 29.2% on the left, and 20.8% bilateral, distributed across hilar 29.2%, lower polar 29.2%, and upper polar 41.7% regions. No significant associations were found between accessory renal arteries and age or gender (p-value > 0.05). However, participants with accessory renal arteries exhibited significantly narrower width 5.0 ± 1.4 than those with no with accessory renal arteries 5.8 ± 1.1 (p-value 0.002) Early dividing renal arteries were found in 5% of participants, with nearly half being bilateral. No significant associations were found between the presence of early dividing renal arteries and demographic or renal measurements (p-value > 0.05).

Conclusion
This study provides valuable insights into the prevalence and characteristics of renal artery variations in a Sudanese population. The findings contribute to our understanding of renal anatomy in this demographic and can inform clinical practice and surgical planning, particularly in renal transplantation and other renal procedures.
Impact of hepatic inflammation and fibrosis on the recurrence and long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after hepatectomy
Authors: Hao Xiangyong , Xu Liangliang , Lan Xiang , Li Bo , Cai Hui 
Published: April 2024

Abstract
Background
Underlying liver disease is correlated with hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV) infection. However, the impact of hepatic inflammation and fibrosis on the patients’ prognoses remains unclear.

Methods
The clinicopathological data of 638 HBV-infected patients with early-stage HCC between 2017 and 2019 were prospectively collected. Hepatic inflammation and fibrosis were evaluated by experienced pathologists using the Scheuer score system. Survival analysis was analyzed using the Kaplan–Meier analysis.

Results
Application of the Scheuer scoring system revealed that 50 (7.9%), 274 (42.9%), and 314 (49.2%) patients had minor, intermediate, and severe hepatic inflammation, respectively, and 125 (15.6%), 150 (23.5%), and 363 (56.9%) patients had minor fibrosis, advanced fibrosis, and cirrhosis, respectively. Patients with severe hepatitis tended to have a higher rate of HBeAg positivity, higher HBV-DNA load, elevated alanine aminotransferase (ALT) levels, and a lower proportion of capsule invasion (all Pp < 0.05). There were no significant differences in the recurrence-free and overall survival among the three groups (P = 0.52 and P = 0.66, respectively). Patients with advanced fibrosis or cirrhosis had a higher proportion of HBeAg positivity and thrombocytopenia, higher FIB-4, and larger tumor size compared to those with minor fibrosis (all P < 0.05). Patients with minor, advanced fibrosis, and cirrhosis had similar prognoses after hepatectomy (P = 0.48 and P = 0.70). The multivariate analysis results indicated that neither hepatic inflammation nor fibrosis was an independent predictor associated with prognosis.

Conclusions
For HBV-related HCC patients receiving antiviral therapy, hepatic inflammation and fibrosis had little impact on the post-hepatectomy prognosis.
Survival analysis of Sudanese oral squamous cell carcinoma patients with field of cancerization
Authors: Eltohami Yousif , Suleiman Ahmed 
Published: April 2024

Abstract
Background
The late presentation and diagnosis of OSCC account for the large number of patients with the advanced form of the disease. In Sudan, cases with delayed presentation, particularly those with risk factors such as Toombak dipping and alcohol consumption, frequently present with extensive lesions and a wide area of Field cancerization which characterized by the presence of genetic and epigenetic changes in histologically normal-appearing tissues, and have increased risk for recurrent and second primary tumors. This necessitates more aggressive treatment and is usually associated with poorer outcomes. The present study aims to investigate the survival of oral squamous cell carcinoma patients with a wide field of cancerization.

Methods
This prospective longitudinal study includes ninety-three oral cancer patients with extensive fields of cancerization who underwent surgical treatment at Khartoum Teaching Dental Hospital (KTDH) conducted from 2019 to 2023. These patients were regularly assessed for clinical changes such as recurrence, the development of second primary tumours, and overall survival over a period of one year.

Results
Out of the 93 patients, 57 (61.3%) were males, and 36 (38.7%) were females. The majority of the patients (82%) had stage IV tumours, and 62.3% had nodal metastasis. Twenty-eight (30%) patients developed recurrences, and 14 (15%) developed second primary tumours. The overall one-year survival rate was 89%, and all deceased patients passed away within 12 months. The survival rate for patients with different types of recurrences varied, with patients who had regional, local, and locoregional recurrences having survival rates of 87%, 74%, and 72%, respectively. Patients who did not experience a recurrence had a one-year survival rate of 92%. Patients who developed second primary tumours had an 86% survival rate. The survival rates for OSCC patients at stages III, IVa, and IVb were 90%, 90%, and 71%, respectively.

Conclusion
In this study, 62% of patients had nodal metastasis, 30% developed recurrence, and 15% developed second primary tumours. The overall one-year survival rate was 89%, although the development of recurrences and second primary tumours had a negative impact on the survival rate.