bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma
Authors: Calitz Carlemi , Rosenquist Jenny , Degerstedt Oliver , Khaled Jaafar , Kopsida Maria , Fryknäs Mårten , Lennernäs Hans , Samanta Ayan , Heindryckx Femke 
Published: January 2023

AbstractThe tumor micro-environment (TME) of hepatocellular carcinoma (HCC) consists out of cirrhotic liver tissue and is characterized by an extensive deposition of extracellular matrix proteins (ECM). The evolution from a reversible fibrotic state to end-stage of liver disease, namely cirrhosis, is characterized by an increased deposition of ECM, as well as changes in the exact ECM composition, which both contribute to an increased liver stiffness and can alter tumor phenotype. The goal of this study was to assess how changes in matrix composition and stiffness influence tumor behavior. HCC-cell lines were grown in a biomimetic hydrogel model resembling the stiffness and composition of a fibrotic or cirrhotic liver. When HCC-cells were grown in a matrix resembling a cirrhotic liver, they increased proliferation and protein content, compared to those grown in a fibrotic environment. Tumour nodules spontaneously formed outside the gels, which appeared earlier in cirrhotic conditions and were significantly larger compared to those found outside fibrotic gels. These tumor nodules had an increased expression of markers related to epithelial-to-mesenchymal transition (EMT), when comparing cirrhotic to fibrotic gels. HCC-cells grown in cirrhotic gels were also more resistant to doxorubicin compared with those grown in fibrotic gels or in 2D. Therefore, altering ECM composition affects tumor behavior, for instance by increasing pro-metastatic potential, inducing EMT and reducing response to chemotherapy.
Investigation of early molecular alterations in tauopathy with generative adversarial networks
Authors: Kim Hyerin , Kim Yongjin , Lee Chung-Yeol , Kim Do-Geun , Cheon Mookyung 
Published: January 2023

AbstractThe recent advances in deep learning-based approaches hold great promise for unravelling biological mechanisms, discovering biomarkers, and predicting gene function. Here, we deployed a deep generative model for simulating the molecular progression of tauopathy and dissecting its early features. We applied generative adversarial networks (GANs) for bulk RNA-seq analysis in a mouse model of tauopathy (TPR50-P301S). The union set of differentially expressed genes from four comparisons (two phenotypes with two time points) was used as input training data. We devised four-way transition curves for a virtual simulation of disease progression, clustered and grouped the curves by patterns, and identified eight distinct pattern groups showing different biological features from Gene Ontology enrichment analyses. Genes that were upregulated in early tauopathy were associated with vasculature development, and these changes preceded immune responses. We confirmed significant disease-associated differences in the public human data for the genes of the different pattern groups. Validation with weighted gene co-expression network analysis suggested that our GAN-based approach can be used to detect distinct patterns of early molecular changes during disease progression, which may be extremely difficult in in vivo experiments. The generative model is a valid systematic approach for exploring the sequential cascades of mechanisms and targeting early molecular events related to dementia.
Validation of data mining models by comparing with conventional methods for dental age estimation in Korean juveniles and young adults
Authors: Kumagai Akiko , Jeong Seoi , Kim Daeyoun , Kong Hyoun-Joong , Oh Sehyun , Lee Sang-Seob 
Published: January 2023

AbstractTeeth are known to be the most accurate age indicators of human body and are frequently applied in forensic age estimation. We aimed to validate data mining-based dental age estimation, by comparing the accuracy of the estimation and classification performance of 18-year thresholds with conventional methods and with data mining-based age estimation. A total of 2657 panoramic radiographs were collected from Koreans and Japanese populations aged 15 to 23 years. They were subdivided into a training and internal test set of 900 radiographs each from Koreans, and an external test set of 857 radiographs from Japanese. We compared the accuracy and classification performance of the test sets from conventional methods with those from the data mining models. The accuracy of the conventional method with the internal test set was slightly higher than that of the data mining models, with a slight difference (mean absolute error < 0.21 years, root mean square error < 0.24 years). The classification performance of the 18-year threshold was also similar between the conventional method and the data mining models. Thus, conventional methods can be replaced by data mining models in forensic age estimation using second and third molar maturity of Korean juveniles and young adults.
Genome-wide siRNA screens identify RBBP9 function as a potential target in Fanconi anaemia-deficient head-and-neck squamous cell carcinoma
Authors: Pai Govind , Roohollahi Khashayar , Rockx Davy , de Jong Yvonne , Stoepker Chantal , Pennings Charlotte , Rooimans Martin , Vriend Lianne , Piersma Sander , Jimenez Connie R. , De Menezes Renee X. , Van Beusechem Victor W. , Brakenhoff Ruud H. , Te Riele Hein , Wolthuis Rob M. F. , Dorsman Josephine C. 
Published: January 2023

AbstractFanconi anaemia (FA) is a rare chromosomal-instability syndrome caused by mutations of any of the 22 known FA DNA-repair genes. FA individuals have an increased risk of head-and-neck squamous-cell-carcinomas (HNSCC), often fatal. Systemic intolerance to standard cisplatin-based protocols due to somatic-cell hypersensitivity underscores the urgent need to develop novel therapies. Here, we performed unbiased siRNA screens to unveil genetic interactions synthetic-lethal with FA-pathway deficiency in FA-patient HNSCC cell lines. We identified based on differential-lethality scores between FA-deficient and FA-proficient cells, next to common-essential genes such as PSMC1, PSMB2, and LAMTOR2, the otherwise non-essential RBBP9 gene. Accordingly, low dose of the FDA-approved RBBP9-targeting drug Emetine kills FA-HNSCC. Importantly both RBBP9-silencing as well as Emetine spared non-tumour FA cells. This study provides a minable genome-wide analyses of vulnerabilities to address treatment challenges in FA-HNSCC. Our investigation divulges a DNA-cross-link-repair independent lead, RBBP9, for targeted treatment of FA-HNSCCs without systemic toxicity.
Mechanical compression creates a quiescent muscle stem cell niche
Authors: Tao Jiaxiang , Choudhury Mohammad Ikbal , Maity Debonil , Kim Taeki , Sun Sean X. , Fan Chen-Ming 
Published: January 2023

AbstractTissue stem cell niches are regulated by their mechanical environment, notably the extracellular matrix (ECM). Skeletal muscles consist of bundled myofibers for force transmission. Within this macroscopic architecture, quiescent Pax7-expressing (Pax7+) muscle stem cells (MuSCs) are compressed between ECM basally and myofiber apically. Muscle injury causes MuSCs to lose apical compression from the myofiber and re-enter the cell cycle for regeneration. While ECM elasticities have been shown to affect MuSC’s renewal, the significance of apical compression remains unknown. To investigate the role of apical compression, we simulate the MuSCs’ in vivo mechanical environment by applying physical compression to MuSCs’ apical surface. We demonstrate that compression drives activated MuSCs back to a quiescent stem cell state, regardless of basal elasticities and chemistries. By mathematical modeling and cell tension manipulation, we conclude that low overall tension combined with high axial tension generated by compression leads to MuSCs’ stemness and quiescence. Unexpectedly, we discovered that apical compression results in up-regulation of Notch downstream genes, accompanied by the increased levels of nuclear Notch1&3 in a Delta ligand (Dll) and ADAM10/17 independent manner. Our results fill a knowledge gap on the role of apical compression for MuSC fate and have implications to stem cells in other tissues.
The neoepitope of the complement C5b-9 Membrane Attack Complex is formed by proximity of adjacent ancillary regions of C9
Authors: Bayly-Jones Charles , Ho Bill H. T. , Lau Corinna , Leung Eleanor W. W. , D’Andrea Laura , Lupton Christopher J. , Ekkel Susan M. , Venugopal Hariprasad , Whisstock James C. , Mollnes Tom E. , Spicer Bradley A. , Dunstone Michelle A. 
Published: January 2023

AbstractThe Membrane Attack Complex (MAC) is responsible for forming large β-barrel channels in the membranes of pathogens, such as gram-negative bacteria. Off-target MAC assembly on endogenous tissue is associated with inflammatory diseases and cancer. Accordingly, a human C5b-9 specific antibody, aE11, has been developed that detects a neoepitope exposed in C9 when it is incorporated into the C5b-9 complex, but not present in the plasma native C9. For nearly four decades aE11 has been routinely used to study complement, MAC-related inflammation, and pathophysiology. However, the identity of C9 neoepitope remains unknown. Here, we determined the cryo-EM structure of aE11 in complex with polyC9 at 3.2 Å resolution. The aE11 binding site is formed by two separate surfaces of the oligomeric C9 periphery and is therefore a discontinuous quaternary epitope. These surfaces are contributed by portions of the adjacent TSP1, LDLRA, and MACPF domains of two neighbouring C9 protomers. By substituting key antibody interacting residues to the murine orthologue, we validated the unusual binding modality of aE11. Furthermore, aE11 can recognise a partial epitope in purified monomeric C9 in vitro, albeit weakly. Taken together, our results reveal the structural basis for MAC recognition by aE11.
Anti‐noise diesel engine misfire diagnosis using a multi‐scale CNN‐LSTM neural network with denoising module
Authors: Qin Chengjin , Jin Yanrui , Zhang Zhinan , Yu Honggan , Tao Jianfeng , Sun Hao , Liu Chengliang 
Published: January 2023

AbstractCurrently, accuracy of existing diesel engine fault diagnosis methods under strong noise and generalisation performance between different noise levels are still limited. A novel multi‐scale CNN‐LSTM neural network (MSCNN‐LSTMNet) is proposed with a residual‐CNN denoising module for anti‐noise diesel engine misfire diagnosis. First, a residual‐CNN module is designed for denoising the original vibration signal measured from the diesel engine cylinder and residual loss for constructing a new loss function is utilised. Considering the essential characteristics of measured vibration signals at different scales, a multi‐scale convolutional NN (CNN) block is designed to realize multi‐scale feature extraction. Specifically, multiple convolution layers with different branches and different convolution kernel sizes are utilised to extract different time scales features, enhancing the robustness of the model. On this basis, the LSTM is utilised to further extract sequential features for improving anti‐noise and generalisation performances. The effectiveness of MSCNN‐LSTMNet is validated by experimental results of both one‐ and hybrid‐cylinder diesel engine misfires diagnosis under various noise levels and working conditions. The results demonstrate that MSCNN‐LSTMNet achieved much better anti‐noise and generalisation performances than the existing methods. Under strong noise conditions (−10 dB signal‐to‐noise ratio) for four datasets, MSCNN‐LSTMNet obtained 97.561% average accuracy, while average accuracy for random forest, deep neural network, CNN and MSCNNNet were 73.828%, 79.544%, 82.247%, and 89.741%, respectively. Moreover, for 11 noise generalisation tasks between different noise levels, MSCNN‐LSTMNet obtained at least 96.679%, 97.849%, 98.892%, and 94.010% accuracy on the four datasets, which are much higher than those of the existing methods.
Exploring extreme conditions for star formation: A deep search for molecular gas in the Leo ring
Authors: Corbelli Edvige , Thilker David , Mannucci Filippo , Cresci Giovanni 
Published: January 2023

Aims. We carried out sensitive searches for the 12CO J = 1–0 and J = 2–1 lines in the giant extragalactic HI ring in Leo to investigate the star formation process within environments where gas metallicities are close to solar, but physical conditions are different than those typical of bright galaxy disks. Our aim is to check the range of validity of known scaling relations.
Methods. We used the IRAM-30 m telescope to observe 11 regions close to HI gas peaks or where sparse young massive stars have been found. For all pointed observations we reached spectral noise between 1 and 5 mK for at least one of the observed frequencies at 2 km s−1 spectral resolution.
Results. We marginally detect two 12CO J = 1–0 lines in the star-forming region Clump 1 of the Leo ring, whose radial velocities are consistent with those of Hα lines, but whose line widths are much smaller than observed for virialized molecular clouds of similar mass in galaxies. The low signal-to-noise ratio, the small line widths, and the extremely low number densities inferred by virialized cloud models suggest that a more standard population of molecular clouds, still undetected, might be in place. Using upper limits to the CO lines, the most sensitive pointed observations show that the molecular gas mass surface density is lower than expected from the extrapolation of the molecular Kennicutt–Schmidt relation established in the disk of galaxies. The sparse stellar population in the ring, possibly forming ultra diffuse dwarf galaxies, might then be the result of a short molecular gas depletion time in this extreme environment.
Alternative Strategy for Teaching and Learning during COVID-19 pandemic – A case study from Middle East College, OMAN
Authors: Najah Samiha , Rao Vikas , Al Qassabi Suad 
Published: January 2023

Education witnessed great evolution thanks to Technological advances (Raja and Nagasubramani 2018). Although Online learning has many benefits such as flexibility and scalability, many higher education institutions do not opt to it since it was considered less effective than traditional classrooms. The outbreak of COVID19 pandemic and Social distancing measures taken in most countries in the world have revived the need for Online learning and greatly impacted the educational landscape.
In this research, we target to study the effectiveness of online teaching through a case study from Middle East College during Spring 2020 semester. A layered approach has been adopted in the form of methodology which could be further elaborated and customized as per the nature and level of module. To this end, assessment of online teaching implementation from both teacher’s point of view and student’s perspective have been accomplished. Challenges will then be analyzed and recommendations in the future will be suggested.
Transitioning from Pandemic to Endemic Pedagogy: Redesigning Teaching and Learning
Authors: Farrag Siham G. , Abushammala Mohammed F. , Kuckian Sachin 
Published: January 2023

COVID-19 was declared a pandemic by the World Health Organization in 2020. A year later, we consider the shift and accept the necessity of continually re-imagining blended learning for life and work in the wake of COVID-19. This paper offers strategies initiated in teaching and learning at Middle East College, Muscat, Sultanate of Oman, during and post-pandemic. This research also shows how these changes have affected students' learning. It involved three stages of Practise: Surviving during the pandemic without compromising on any loss of education, managing continuity, and accelerating the education system by using the opportunity.
All students registered in the Civil Engineering Programme in the Spring 2020, Spring 2021, and Spring 2022 semesters were involved in this study. The teaching and learning practise was evaluated utilising quantitative and qualitative methods. The quantitative method involved the students' performance in the assessment and findings from the survey. The qualitative method includes online analysis of students' feedback through Blitz Survey and Module Evaluation Survey (MES) by the Quality Assurance Office (QAO). The results indicated the approach adopted was quite effective in enhancing students' learning. The findings support the intuition of teachers seeking to help their students become digitally fluent in creating better tools and methods to support effective blended teaching and learning.
Tubercular Subdural Empyema with Tubercular Abscess: Lessons Learnt
Authors: Pannem Rajkumar , Kanderia Ridham Ashokbhai , Arora Rajnish Kumar , Mittal Radhey Shyam 
Published: January 2023

AbstractTuberculosis (TB) is still one of the major health care problems in many developing countries. Among various forms of TB, central nervous system (CNS) TB causes significant morbidity and mortality. CNS TB can present in various forms: cerebritis, abscess, meningitis, tuberculoma, calcified granuloma, meningitis, or hydrocephalus. But subdural empyema is a very rare form of presentation. Very few cases have been reported till now in the literature. So, high level of suspicion, thorough microbiological and histological investigations to diagnosis, and early and timely inception of anti-TB medication are keys in its management. Here, we are presenting a case of tubercular subdural empyema that was successfully treated with surgical evacuation and anti-TB medication.
Comparison of Bretschneider HTK and Blood Cardioplegia (4:1): A Prospective Randomized Study
Authors: Ak Koray , Dericioğlu Okan , Midi Ahmet , Kararmaz Alper , Er Zafer , Doğusan Zeynep , Arsan Sinan 
Published: January 2023

Abstract
Background We compared the effect of intermittent blood and histidine-tryptophan-ketoglutarate (HTK) solution of Bretschneider on myocardial histopathology and perioperative outcome.
Methods Forty adult cardiac surgery patients were grouped into two (n = 20 for each): (1) Intermittent blood cardioplegia (IBC): had repeated cold 4:1 blood cardioplegia and (2) HTK: had a single dose of cold HTK for cardioprotection. Creatine kinase (CK)-MB, Troponin-I (cTn-I), pH, and lactate were studied in coronary sinus blood before and after aortic cross-clamping (AXC) and systemic blood at postoperative 6th, 24th, and 48th hours. Myocardial biopsy was performed before and after AXC for light microscopy. Vacuolation, inflammation, edema, and glycogen were graded semiquantitatively (from 0 to 3). The myocardial apoptotic index was evaluated via the terminal deoxynucleotidyl transferase dUTP nick end labeling.
Results There were no differences in perioperative clinical outcomes between the groups. The coronary sinus samples after AXC were more acidotic (7.15 ± 0.14 vs. 7.32 ± 0.07, p = 0.001) and revealed higher CK-MB (21.0 ± 12.81 vs. 12.60 ± 11.80, p = 0.008) in HTK compared with IBC. The HTK had significantly a higher amount of erythrocyte suspension intraoperatively compared with IBC (0.21 ± 0.53 vs. 1.68 ± 0.93 U, p = 0.001). Microscopically, myocardial edema was more pronounced in HTK compared with IBC after AXC (2.25 ± 0.91 vs. 1.50 ± 0.04, p = 0.013). While a significant increase in the apoptotic index was seen after AXC in both groups (p = 0.001), no difference was detected between the groups (p = 0.417).
Conclusion IBC and HTK have a similar clinical outcome and protective effect, except for more pronounced myocardial edema and increased need for intraoperative transfusion with HTK.
Comparison of Endoscopic Ultrasound-Guided Fine-Needle Aspiration with Fine-Needle Biopsy for Solid Gastrointestinal Lesions: A Randomized Crossover Single-Center study
Authors: Afzalpurkar Shivaraj , Rai Vijay Kumar , Sonthalia Nikhil , Rodge Gajanan , Tewary Awanesh , Goenka Mahesh 
Published: January 2023

Abstract
Background/Aims The purpose of this study was to compare the results of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) and fine-needle biopsy (FNB) performed at the same site in a single session in the same patient.
Methods Consecutive patients with solid gastrointestinal lesions referred for EUS evaluation underwent EUS-FNA and FNB using 22G needles with three and two passes, respectively, in the same session. Patients were randomized to one group having EUS-FNA first followed by EUS-FNB, while other group had EUS-FNB first followed by EUS-FNA.
Results Total 50 patients (31 male) of mean age 56.58 ± 14.2 years and mean lesion size of 2.6 (±2) cm were included. The Kappa agreement for final diagnosis for FNA and FNB was 0.841 and 0.61, respectively. The sensitivity and specificity of FNA versus FNB were 85.19 versus 62.96% and 100 versus 100%, respectively, in comparison with final diagnosis.
Conclusion Both EUS-FNA and FNB are equally safe when compared between the two techniques simultaneously in same lesion. EUS-FNA is better than FNB in terms of sensitivity, diagnostic accuracy, and tissue yield for solid GI lesion. However, the specificity and positive predictive value were equally good for both the modalities.
Performance of the Mean, Highest, and Admission Day Pediatric Sequential Organ Failure Assessment Scores As Outcome Predictors in a Pediatric Intensive Care Unit: A Prospective Observational Study
Authors: Maity Debasis , Samanta Moumita , Sen Sandipan , SinhaMahapatra Tapan Kumar , Mallick Asim Kumar 
Published: January 2023

AbstractThe pediatric sequential organ failure assessment (pSOFA) score has been recently validated from its adult version having included the six clinical and biochemical parameters of organ dysfunction (respiratory, coagulation, cardiovascular, neurological, hepatic, and renal) and adapting age-adjusted cutoffs. Our goal was to find out which among the pSOFA scores (recorded on admission, highest score, and the mean score i.e., pSOFA1, pSOFAh, and pSOFAm respectively) performed better to predict mortality among the patients admitted in our pediatric intensive care unit (PICU). This prospective observational study was conducted on 104 patients (1 month to 12 years of age) admitted in the eight bedded PICU of a tertiary care hospital in India who met the inclusion criteria. The highest values of serial pSOFA scores were recorded on every alternate day starting from the day of admission up to day 9. The mean and median values of the pSOFA1, pSOFAm, and pSOFAh were higher in the nonsurvivor group than in the survivors. The mean pSOFA (with a diagnostic accuracy of 92.3% at a mean cut-off value of 12.8) has outperformed the other two pSOFA scores. In this exploratory analysis, the pSOFAm is the best tool in predicting the mortality outcome of any critically ill child. The use of the pSOFA score at admission and the mean values helps the clinician to quantify the organ dysfunction, and it may be helpful for the clinicians to take steps for further management. It may be useful to communicate to the parents of the sick child for prognostication too. The pSOFA1 also reflects well on the early prognostication when multiple pSOFA scores are unavailable. In the resource constraint settings, one may rely on the pSOFA1 and the approximate pSOFAm value may be predicted from the pSOFA1 as pSOFAm=[(1.03 XpSOFA1) – 0.9] within limitations.