bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating microbial profiling and machine learning for inference of drowning sites: a forensic investigation in the Northwest River
Authors: Su Qin , Zhang Xiaofeng , Chen Xiaohui , Yu Zhonghao , Wu Weibin , Xiang Qingqing , Yang Chengliang , Zhao Jian , Chen Ling , Xu Quyi , Liu Chao 
Published: December 2024

ABSTRACT

Drowning incidents present significant challenges for forensic investigators in determining the exact site of occurrence. Traditional forensic methods often rely on physical evidence and circumstantial clues, but the emerging field of forensic microbiology offers a promising avenue for enhancing precision and reliability in site inference. Our study investigates the application of microbiome analysis in inferring drowning sites, focusing on microbial diversity in water samples and lung tissues of drowned animals from different sites in the Northwest River. We utilized 16S rDNA sequencing to analyze microbial diversity in water samples and lung tissues, revealing distinct microbial signatures associated with drowning sites. Our findings highlight variations in species richness and diversity across different sampling points, indicating the influence of environmental factors on microbial community structure. Machine learning models trained on microbial data from lung tissues demonstrated high accuracy in predicting drowning sites, with cross-validation accuracy ranging from 83.53% ± 3.99% to 95.07% ± 3.17%. Notably, the Gradient Boosting Machine (GBM) method achieved a classification accuracy of 95.07% ± 3.17% for different sampling points at a submersion time of 1 day. Moreover, our cross-species site inference results revealed that utilizing data from drowned mice to predict the drowning sites of rabbits in location W5 achieved an accuracy of 72.22%. In conclusion, our study underscores the potential of microbiome analysis in forensic investigations of drowning incidents. By integrating microbial data with traditional forensic techniques, there is significant potential to enhance the reliability of scene inferences, thereby making substantial contributions to case investigations and judicial trials.

IMPORTANCE
By employing advanced techniques like microbial profiling and machine learning, the study aims to enhance the accuracy of determining drowning sites, which is crucial for both legal proceedings. By analyzing microbial diversity in water samples and drowned animal lung tissues, the study sheds light on how environmental factors and victim-related variables influence microbial communities. The findings not only advance our understanding of forensic microbiology but also offer practical implications for improving investigative techniques in cases of drowning.
Emergency clinician perceptions of end-of-life care in Irish emergency departments: a cross-sectional survey
Authors: Foley James , Umana Etimbuk , Saeed Saema , Mulcaire Jeffrey , Keane Owen , Browne Leonard , O' Leary Mary Jane , Deasy Conor 
Published: December 2024

BackgroundPatients with end-of-life care (EoLC) needs present to the emergency departments (ED) frequently and at times, it can be difficult to provide a high standard of care. Within the Irish setting, there is limited literature on the provision of EoLC in EDs and this study, therefore, aimed to evaluate the perceptions of emergency medicine (EM) clinicians regarding the provision of EoLC in EDs in Ireland.MethodsThe End-of-Life Care in Emergency Department Study was a cross-sectional electronic survey study of EM doctors working across 23 of the 29 EDs in the Ireland. This study was conducted through the Irish Trainee Emergency Research Network over a 6-week period from 27 September 2021 to 8 November 2021. Analysis of the survey domains regarding knowledge and attitude has been published previously by the present authors, with this current analysis focusing on communication, education and resources for the provision of EoLC in EDs. Descriptive data on outcomes are reported with additional subgroup analysis according to years of experience in EM.ResultsOf the 694 potential respondents, 311 (44.8%) had fully completed surveys. The majority (62% n=193) were between 25 and 35 years of age with 60% (n=186) having <5 years’ experience in EM; 58% (n=180) were men. Experienced respondents (>10 years’ experience) were more likely to agree that they were comfortable discussing EoL with patients and families than those with <5 years’ experience (80% vs 32%) (p<0.001). Questions on ED infrastructure revealed that just 23.5% agreed that appropriate rooms are allocated for EoL patients, with just 11.6% agreeing that the physical environment is conducive to the provision of EoLC.ConclusionEM clinicians agree that they are comfortable breaking bad news and discussing EoLC with patients and families, but disagree that adequate resources and infrastructure are in place to provide a high standard of EoLC in Irish EDs. Challenges exist centred on training and infrastructure and addressing these may lead to enhanced EoLC in the future.
Sports Image Feature Extraction Based on Machine Learning and Global Search Algorithm
Authors: Li Haiting , Yan Jinghao 
Published: December 2024

This study utilizes a combination of machine learning and a global search algorithm to enhance the quality of feature extraction in sports images. A deep residual generative adversarial network is employed to deblur images and sharpen their clarity, while the optimized particle swarm optimization algorithm is utilized to extract image features with precision and identify critical information. According to the experimental results, the research method improves the peak signal-to-noise ratios in ball sports image deblurring by 12.45%, 13.91%, and 17.18%, respectively, and in track and field sports image deblurring by 11.71%, 12.91%, and 21.61%, respectively, when compared with the generative adversarial network, generative adversarial network incorporating the attention mechanism, and multi-scale convolution-based algorithm. The accuracy-recall curve of the particle swarm algorithm that has been optimised for research completely encircles the accuracy-recall curves of the other four algorithms, which verifies the efficacy of the research methodology. The research will offer a more comprehensive perspective on sports image processing.
Adolescents’ Sexual Reproductive Health Service Utilization and Associated Factors Among Bahir Dar City High School Students, Amhara Region, Ethiopia: A Cross‐Sectional Study
Authors: Elefachew Addis , Alemu Yibeltal , Chanie Belaynesh , Getachew Eyob , Bogale Solomon Ketema , Bogale Eyob Ketema 
Published: December 2024

Introduction: All across the world, youths struggle with a variety of health issues. Adolescents everywhere are entering puberty earlier and engaging in more premarital sex. There was limited evidence about the current adolescent sexual reproductive health (RH) service utilization status and its associated factors in the study area, especially after the occurrence of COVID‐19 and the war between the Ethiopian federal government and Tigray regional forces.Objective: The study is aimed at assessing the magnitude of sexual RH service utilization and associated factors among Bahir Dar City high school students, Amhara region, Ethiopia, in 2022.Methods: An institution‐based cross‐sectional study design was conducted among Bahir Dar City high school students from December 18, 2022, to January 12, 2022. A multistage sampling technique was applied to select study participants. A total of 629 respondents participated in the study. The data were collected using a pretested, structured, self‐administered questionnaire. The data were entered into EpiData Version 3.1 and then exported to SPSS Version 25 for analysis. Bivariable and multivariable logistic regression was used for analysis.Results: The magnitude of adolescent sexual RH service utilization was found to be 30.4%. School RH club participation (AOR = 5.93, CI: 3.29–10.71), having ever had sexual exposure (AOR = 6.03, CI: 3.31–10.98), history of sexual RH problems (AOR = 3.26, CI: 1.41–7.51), being perceived as at risk of sexual RH problems (AOR = 6, CI: 3.26–11.04), hearing information about adolescent sexual RH (AOR = 5.19, CI: 3–8.97), and knowing the place to use RH service (AOR = 2.37, CI: 1.47–3.82) were associated with utilization of adolescent sexual RH service.Conclusions: The magnitude of adolescent sexual RH service utilization was found to be 30.4%. School RH club participation, having ever had sexual exposure, a history of sexual RH problems, being perceived as at risk of sexual RH problems, hearing information about sexual RH, and knowing the place where to get RH services were associated with the utilization of sexual RH services.
Development and Psychometric Evaluation of a Questionnaire to Assess Attitudes Towards Invisible Gender‐Based Violence (Q‐AIGV)
Authors: Fernández-Férez Alba , Fernández-Vargas Anabel , Dobarrio-Sanz Iria , Ochoa-Pineda Amada Cesibel , Abarca-Duran Ximena , Martínez-Abarca Ana Lucía , Fernández-Sola Cayetano , Hernández-Padilla José Manuel 
Published: December 2024

Objective: To develop and psychometrically evaluate a questionnaire to assess attitudes towards invisible gender‐based violence (Q‐AIGV).Background: Invisible gender‐based violence is defined as discriminatory attitudes and beliefs towards women that are culturally accepted and normalised in society.Methodology: This is a cross‐sectional descriptive observational study. The development of the initial version of the questionnaire, a pilot study (N = 63) and a final validation study (N = 1264) were carried out. Reliability, validity, stability and readability were tested.Results: Exploratory factor analysis revealed that the Q‐AIGV is composed of 15 items distributed in three factors. Known‐groups analysis detected significant differences in two groups with different characteristics (age and relationship duration). Criterion validity indicated the existence of a moderate and significant correlation (r = 0.469; p < 0.001) between the mean score of the Q‐AIGV and the ‘Scale of Attitudes towards Gender‐based Violence’. The Q‐AIGV’s content validity index (CVI‐t = 0.96) and internal consistency (α = 0.906) were excellent.Conclusion: The Q‐AIGV showed very good results for reliability, validity, stability and readability. This suggests that the Q‐AIGV could be a good tool for assessing attitudes towards invisible gender‐based violence.
Gain-of-Function Chromatin Remodeling Activity of Oncogenic FOXL2-C134W Reprograms Glucocorticoid Receptor Occupancy to Drive Granulosa Cell Tumors
Authors: Welte Thomas , Vuttaradhi Veena K. , Khlebus Eleonora Y. , Brodsky Allison , Flores Legarreta Alejandra , Celestino Joseph , Powell Reid T. , Stephan Clifford C. , Nguyen Nghi , Li Jian , Takamatsu Shiro , Calzoncinth Katherine , Sood Anil K. , Gershenson David M. , Futreal P. Andrew , Lawson Barrett , Hillman Robert Tyler. 
Published: December 2024

Abstract
Adult type ovarian granulosa cell tumors (AGCTs) are rare malignancies with the near universal c.C402G (p.Cys134Trp) somatic mutation in FOXL2, a Forkhead box-family transcription factor important for ovarian function. Relapsed AGCT is incurable, but the mechanism of the unique FOXL2 mutation could confer therapeutic vulnerabilities. To identify FOXL2-C134W-dependent pharmacologic synergies, we created and characterized endogenous FOXL2 isogenic AGCT cells and an AGCT tumoroid biobank. A drug screen identified that glucocorticoids promote FOXL2-C134W-dependent AGCT growth. Epigenetic investigation revealed that the Cys134Trp mutation exposes latent DNA sequence-specific chromatin remodeling activity in FOXL2. FOXL2-C134W-dependent chromatin remodeling activity redirected glucocorticoid receptor chromatin occupancy to drive hyaluronan synthase 2 gene expression and increase extracellular hyaluronan secretion. Treatment of AGCT models with hyaluronidase reduced viability, and dexamethasone rescued this effect. Combinatorial drug-drug interaction experiments demonstrated that dexamethasone antagonizes the potency of paclitaxel, a chemotherapy agent frequently used in the treatment of AGCT. Thus, gain-of-function pioneering activity contributes to the oncogenic mechanism of FOXL2-C134W and creates a potentially targetable synergy with glucocorticoid signaling.
Abstract A002: Computational identification for missense mutations of bladder cancer candidate genes using TCGA datasets
Authors: He Kai , Wang Lucas , Bai Yongsheng 
Published: December 2024

Abstract
Bladder cancer is the fourth most common cancer in men. According to the American Cancer Society, there were roughly over 80,000 cases in the United States in 2023, and nine out of ten people with this cancer are over the age of 55. The Cancer Genome Atlas (TCGA) project has made it possible for researchers to study mutations and other types of genetic signatures for multiple cancers including Bladder Urothelial Carcinoma (BLCA). A missense mutation is where a single nucleotide change in the DNA sequence results in the substitution of one amino acid for another in the protein. This could lead to a protein with an altered function. The impact of a missense mutation could be benign or harmful. In our previous study, 54 significant clusters for 15 cancer types were identified in The Cancer Genome Atlas (TCGA) network. In this study, we further investigated genes in two significant clusters reported for BLCA. We initially aim to identify genes that have missense mutations that have functional impact. To achieve this goal, we plugged the two clusters of genes (199) into the cBioPortal website and identified eight genes that had missense mutations or met three criteria (Firstly, numbers of mutations in sample must be greater than or equal to 5; secondly, functional impact must meet the following both: SIFT impact is deleterious and Polyphen-2 impact is possibly damaging or probably damaging): AKT3, PARP1, PRKN, APC, GNA11, KMT2A, NEGR1, and FYN. Further analysis showed what specific amino acid had been substituted at what specific position on the sequence. For example, for gene AKT3, at position 286, amino acid K had been substituted into amino acid N. Similarly, for gene PARP1, at position 913, amino acid G had been substituted into amino acid A. We then identified every amino acid missense substitution for all eight genes. By examining the mutation pattern, we hope to identify key genes as biomarkers so that therapeutic efficacy can be optimized.
Citation Format: Kai He, Lucas Wang, Yongsheng Bai. Computational identification for missense mutations of bladder cancer candidate genes using TCGA datasets. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A002
Abstract A015: Design and deciphering of precision peptide inhibitors for cancer stemness using generative deep learning and molecular dynamics simulations
Authors: Selvaraj Gurudeeban , Kaliamurthi Satyavani , Peslherbe Gilles H. 
Published: December 2024

Abstract
The use of artificial intelligence (AI) and machine learning (ML) for exploring vast amino acid sequence spaces has recently gained traction in the discovery of antibiotics and the design of biomaterials with a wide array of algorithms. However, despite some advancements, designing peptide inhibitors to specifically modulate protein-protein interactions remains a significant challenge. In this contribution, we explore the use of a Long Short-Term Memory (LSTM) network - a type of recurrent neural network - to model peptide sequences, given its ability to process sequential data and capture long-term dependencies, critical for peptide design. Our research focuses on developing precision peptides that target the interaction between the Notch intracellular domain (NICD) and CBF1/RBPJ transcription factors, key regulators of the Notch signaling pathway implicated in breast and pancreatic cancer stemness. We inferred hydrophobic, hydrophilic, van der Waals, and salt bridge interactions from experimentally determined three-dimensional protein complex structures, which were used for feature engineering via one-hot encoding. Peptides, each 20 amino acids in length, were generated using temperature scaling in the LSTM model. These peptides were then structurally optimized and subjected to molecular dynamics (MD) simulations, followed by molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) analysis to assess their interactions and binding affinities with the Notch receptor. The MD simulations provide valuable molecular-level insights into the peptide-Notch interactions, helping to evaluate their binding strength. Further biological testing is underway to validate the efficacy of these lead peptide inhibitors and elucidate their molecular mechanisms in targeting cancer stem cells associated with breast cancer.
Citation Format: Gurudeeban Selvaraj, Satyavani Kaliamurthi, Gilles H. Peslherbe. Design and deciphering of precision peptide inhibitors for cancer stemness using generative deep learning and molecular dynamics simulations. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A015
Abstract A016: Targeting calpain-1 and calpain-2 for prevention of breast cancer metastasis: In vivo insights and drug discovery approaches
Authors: Shapovalov Ivan , Poudel Pitambar , Panday Shailesh K. , Harper Danielle , Min Jung Yeon , Gao Yan , Nouri Kazem , Alexov Emil , Greer Peter A. 
Published: December 2024

Abstract
Calpain-1 and calpain-2 are heterodimeric calcium-dependent cysteine proteases composed of the catalytic subunits CAPN1 or CAPN2, respectively, and the common regulatory subunit CAPNS1. They are associated with cancer progression, metastasis, and treatment resistance in breast cancer. Here, we present novel insights into the therapeutic potential of calpain inhibition by combining genetic disruption and preclinical mouse tumor models and biosensor-based detection of calpain heterodimerization with ongoing efforts to discover small-molecule and peptide inhibitors. CRISPR-Cas9-mediated knockout of CAPN1, CAPN2, or CAPNS1 in MDA-MB-231 human triple-negative breast cancer (TNBC) cells revealed that disruption of both calpains, through CAPNS1 knockout, significantly reduced cell migration and inhibited spontaneous metastasis in a mouse orthotopic engraftment model by over 80%. Individual knockouts of CAPN1 or CAPN2 also reduced metastasis but to a lesser extent, highlighting the necessity of dual inhibition for optimal therapeutic effect. In parallel, we have been actively seeking small molecules and peptide inhibitors to target calpain through two approaches: inhibiting the PEF-PEF interaction that mediates heterodimerization using small molecules; and targeting the active site using a calpastatin (CAST)-based peptide. To identify small molecules capable of disrupting the PEF-PEF interaction, we conducted in silico screens of over 3.6 million compounds from several libraries. These compounds were evaluated based on their calculated binding affinity and potential to sterically hinder the conformational changes required for calpain activity. The CAST-based peptide inhibitor was designed based on the active site binding B-domain and tested on a purified calpain-2. These efforts lay the groundwork for novel therapeutic approaches targeting calpain-1 and calpain-2, which have emerged as promising targets for preventing metastasis in TNBC. We will present our progress in identifying and validating these small molecules and peptides for further development.
Citation Format: Ivan Shapovalov, Pitambar Poudel, Shailesh K. Panday, Danielle Harper, Jung Yeon Min, Yan Gao, Kazem Nouri, Emil Alexov, Peter A. Greer. Targeting calpain-1 and calpain-2 for prevention of breast cancer metastasis: In vivo insights and drug discovery approaches. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A016
Abstract A018: Somatic mutations in the PIK3CA gene and its prognostic implications among Ethiopian Breast cancer patients
Authors: Desalegn Woldesonbet Zelalem 
Published: December 2024

Abstract
Purpose: The phosphatidylinositol-4, 5-bisphosphate 3-kinase (PIK3CA), catalytic subunit alpha (c) is frequently mutated in breast cancer (BC). Although the biological impact of PIK3CA mutations in BC has been studied in various parts of the world, limited data is available from sub-Saharan Africa. In this study, the frequency and the prognostic role of PIK3CA mutations were investigated among BC patients from Ethiopia. Objective: The aim of the study was to determine the frequency of PIK3CA mutations and its prognostic role in patients with breast cancer in Ethiopia. Methods: Formalin-fixed paraffin-embedded blocks and fresh frozen BC tissue samples were collected from patients newly diagnosed with BC. Histopathological evaluation was carried out using immunohistochemistry (IHC). PIK3CA mutation profiling was carried out using TaqMan® Mutation detection assay. The association between PIK3CA mutation status and clinical and histopathological features was evaluated. A survival regression (Cox’s model) was employed to assess the effect of PIK3CA mutation and other variables on survival. Results: The prevalence of the PIK3CA mutations was 20.4%. Mutation of the PIK3CA gene was mainly observed among younger (24%), early pT stage (19.4%), and G1/G2 tumors (22.3%). The proportion of mutation was 24.4%, 27.3% and 20% in ER+, PR+ and HER2- tumors, respectively. A marked difference was observed in the PIK3CA mutation frequency across the four major tumor subgroups. However, most of the mutated tumors were found among HR+/HER2− (24.1%) followed by HR+/HER2+ tumors (27.8%). In his study, only TNBC was negatively associated with the proportion of mutation in the PIK3CA gene (p-value= 0.02) in comparison to HR+/HER2- tumors. In multivariate Cox’s regression analysis, the advanced pT stage and HR−/HER2- IHC group independently predicted worse overall survival. However, PIK3CA mutation status was not associated with survival. Conclusions: The PIK3CA mutation was relatively high in HR+ tumors. Mutation rates of PIK3CA in Ethiopian BC tumors are similar to those reported for other populations. This finding highlighted that molecular aberrations including mutations in a specific could give insight on prognosis and clinical outcome.
Citation Format: Zelalem Desalegn Woldesonbet. Somatic mutations in the PIK3CA gene and its prognostic implications among Ethiopian Breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A018.