bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemization of Knowledge: Robust Deep Learning using Hardware-software co-design in Centralized and Federated Settings
Authors: Zhang Ruisi , Hussain Shehzeen , Chen Huili , Javaheripi Mojan , Koushanfar Farinaz
Published: August 2023

Deep learning (DL) models are enabling a significant paradigm shift in a diverse range of fields, including natural language processing and computer vision, as well as the design and automation of complex integrated circuits. While the deep models – and optimizations based on them, e.g., Deep Reinforcement Learning (RL) – demonstrate a superior performance and a great capability for automated representation learning, earlier works have revealed the vulnerability of DL to various attacks. The vulnerabilities include adversarial samples, model poisoning, and fault injection attacks. On the one hand, these security threats could divert the behavior of the DL model and lead to incorrect decisions in critical tasks. On the other hand, the susceptibility of DL to potential attacks might thwart trustworthy technology transfer as well as reliable DL deployment. In this work, we investigate the existing defense techniques to protect DL against the above-mentioned security threats. Particularly, we review end-to-end defense schemes for robust deep learning in both centralized and federated learning settings. Our comprehensive taxonomy and horizontal comparisons reveal an important fact that defense strategies developed using DL/software/hardware co-design outperform the DL/software-only counterparts and show how they can achieve very efficient and latency-optimized defenses for real-world applications. We believe our systemization of knowledge sheds light on the promising performance of hardware-software co-design of DL security methodologies and can guide the development of future defenses.
Acrobats and Safety Nets: Problematizing Large-Scale Agile Software Development
Authors: Rolland Knut H. , Fitzgerald Brian , Dingsøyr Torgeir , Stol Klaas-Jan
Published: August 2023

Agile development methods have become a standard in the software industry, including in large-scale projects. These methods share a set of underlying assumptions that distinguish them from more traditional plan-driven approaches. In this article, we adopt Alvesson and Sandberg's problematization approach to challenge three key assumptions that are prevalent in the large-scale agile literature: (1) agile and plan-driven methods are mutually exclusive; (2) self-managing and hierarchically organized teams are mutually exclusive; and (3) agile methods can scale through simple linear composition. Using a longitudinal case study of large-scale agile development, we describe a series of trigger events and episodes whereby the agile approach was tailored to address the needs of the large-scale development context, which was very much at odds with these fundamental assumptions. We develop a set of new underlying assumptions which suggest that agile and plan-driven practices are mutually enabling and necessary for coordination and scaling in large-scale agile projects. We develop nine propositions for large-scale agile projects based on these new alternative underlying assumptions. Finally, we summarize our theoretical contribution in a generic process model of continuously adjusting agile and plan-driven practices in order to accommodate process challenges in large-scale agile projects.
“It’s Weird That it Knows What I Want”: Usability and Interactions with Copilot for Novice Programmers
Authors: Prather James , Reeves Brent N. , Denny Paul , Becker Brett A. , Leinonen Juho , Luxton-Reilly Andrew , Powell Garrett , Finnie-Ansley James , Santos Eddie Antonio
Published: August 2023

Recent developments in deep learning have resulted in code-generation models that produce source code from natural language and code-based prompts with high accuracy. This is likely to have profound effects in the classroom, where novices learning to code can now use free tools to automatically suggest solutions to programming exercises and assignments. However, little is currently known about how novices interact with these tools in practice. We present the first study that observes students at the introductory level using one such code auto-generating tool, Github Copilot, on a typical introductory programming (CS1) assignment. Through observations and interviews we explore student perceptions of the benefits and pitfalls of this technology for learning, present new observed interaction patterns, and discuss cognitive and metacognitive difficulties faced by students. We consider design implications of these findings, specifically in terms of how tools like Copilot can better support and scaffold the novice programming experience.
A Prospective Cohort Study on the Respiratory Effect on Modified Mallampati Scoring
Authors: Naftalovich Rotem , Oydanich Marko , Adeola Janet , Eloy Jean Daniel , Rodriguez-Correa Daniel , Tewfik George L.
Published: August 2023

Background. Mallampati scoring is a common exam method for evaluating the oropharynx as a part of the airway assessment and for anticipation of difficult intubation. It partitions the oropharynx into 4 categories with scores of 1, 2, 3, and 4. Even though its reliability is known to be limited by confounding factors such as patient positioning, patient phonation, tongue protrusion, and examiner variability, the effect of respiration, i.e., inspiration and expiration, has not yet been formally studied. Methods. Mallampati scores were collected from 100 surgical patients during both inspiration and expiration and later compared to the score obtained in the medical record, determined by a board certified anesthesiologist. Results. Score deviations from the medical record reference were compared for both inspiration and expiration showing that respiration affects Mallampati scores; for some patients, the scores improved (i.e., decreased), while in others they worsened (i.e., increased). The respiratory change effect was quantified and visualized by plotting the area under the curve of the histogram of the deviations. 42% of the patients had a worsening of scores by 1 or 2 points with inspiration while 36% of the patients had a worsening of scores by 1 or 2 points with expiration. Conclusions. Mallampati scoring is commonly used in evaluating the oropharynx as a part of the airway assessment and as a screening tool for difficult intubations. However, as this study points out, the respiratory cycle substantially affects the Mallampati scoring system, with significant deviations of 1 or 2 points. In a scoring system of 4 score categories, these deviations are remarkable.
Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide: Role of the PI3K/Akt and TLR4 Signaling Pathways
Authors: Elbaset Marawan A. , Mohamed Bassim M. S. A. , Moustafa Passant E. , Mansour Dina F. , Afifi Sherif M. , Esatbeyoglu Tuba , Abdelrahman Sahar S. M. , Fayed Hany M.
Published: August 2023

Erythropoietin (EPO) is recognized for its function in erythropoiesis; however, its potential antifibrotic effect against liver fibrosis remains unknown. This study examined whether EPO affects thioacetamide (TAA)-induced liver fibrosis by concentrating on the Toll-like receptor 4 (TLR4) cascade and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway as possible pathways. Male Wistar rats were randomized into four groups, which included: the negative control group, the TAA group (intraperitoneal; TAA 100 mg/kg three times per week for 2 weeks), and EPO-treated groups (150 and 300 IU/kg, i.p.) for 2 weeks after TAA injections. EPO attenuated hepatic fibrosis in a dosage-dependent way, as manifested by the diminution in serum alanine aminotransferase and aspartate aminotransferase activities, as well as the increase in albumin level. EPO inhibited the increase in tissue levels of tumor necrosis factors-α, interleukin-1β, transforming growth factor-β1, and TLR4 and raised tissue levels of PI3K and p-PI3K. EPO antioxidant properties were demonstrated by restoring hepatic glutathione and superoxide dismutase by preventing the accumulation of hepatic malondialdehyde. Further, EPO increased the protein expression of PI3K and Akt and decreased TLR4 protein expression. Immunohistochemically, EPO treatment altered tissue histology and downregulated mitogen-activated protein kinase protein expression. Overall, the research suggested that EPO could prevent TAA-induced hepatic fibrosis through upregulating the PI3K/Akt signaling cascade and downregulation the TLR4 downstream axis.
Nephroprotective Effects of Caffeine, Vanillin, and Their Combination against Experimental AlCl3-Induced Renal Toxicity in Adult Male Wistar Rats
Authors: Afolabi Olakunle Bamikole , Olasehinde Oluwaseun Ruth , Olaoye Oyindamola Adeniyi , Jaiyesimi Kikelomo Folake , Ekakitie Ilobekemen Lisa , Oloyede Omotade Ibidun
Published: August 2023

Aluminum (Al) is known to be a nephrotoxic metal that can cause renal toxicity in both humans and animals. The use of functional foods has been reported to have significance in managing the toxic effects associated with such metals. This study aimed to assess the potential protective effects of caffeine, vanillin, and their combination in mitigating AlCl3-induced renal toxicity in adult male Wistar rats. A total of thirty (30) adult male Wistar rats weighing between 150 and 200 g were randomly divided into five groups, each consisting of six rats (n = 6). Group 1 served as the control, while the remaining treatment groups received a daily oral dose of 100 mg/kg AlCl3 for a duration of 21 days. In addition, groups 3–5 were coadministered 50 mg/kg body weight (bw) of caffeine, vanillin, and a combination (50/50 mg/kg bw) of both substances, respectively. In the results, AlCl3-treated showed a significant (

p

 < 0.05) increase in serum biomarkers such as ALT, ALP, urea, and creatinine, and a significant (

p

 < 0.05) decrease in serum total proteins (TPs). The renal tissue’s antioxidant system, including SOD, CAT, GPx, and GSH, exhibited a significant (

p

 < 0.05) reduction, accompanied by an elevated MDA level. However, the administration of caffeine, vanillin, and their combination resulted in a significant (

p

 < 0.05) decrease in serum ALT, ALP, urea, and creatinine, and a significant (

p

 < 0.05) increase in serum TP. Furthermore, following the treatment, there was a significant (

p

 < 0.05) increase in renal SOD, CAT, GPx, and GSH levels, along with a reduction in the MDA level. In addition, the treatment for 21 days caused a significant (

p

 < 0.05) reversal to the altered histomorphological architecture. These findings suggest that caffeine, vanillin, and their combination could potentially be an effective regimen in managing AlCl3-induced renal toxicity.
Matrix Stiffness Triggers Lipid Metabolic Cross-talk between Tumor and Stromal Cells to Mediate Bevacizumab Resistance in Colorectal Cancer Liver Metastases
Authors: Zheng Yannan , Zhou Rui , Cai Jianan , Yang Nanyan , Wen Zhaowei , Zhang Zhihua , Sun Huiying , Huang Genjie , Guan Yijin , Huang Na , Shi Min , Liao Yulin , Bin Jianping , Liao Wangjun
Published: August 2023

Bevacizumab is an anti-VEGF monoclonal antibody that plays an important role in the combination treatment of advanced colorectal cancer. However, resistance remains a major hurdle limiting bevacizumab efficacy, highlighting the importance of identifying a mechanism of antiangiogenic therapy resistance. Here, we investigated biophysical properties of the extracellular matrix (ECM) related to metabolic processes and acquired resistance to bevacizumab. Evaluation of paired pre- and posttreatment samples of liver metastases from 20 colorectal cancer patients treated with combination bevacizumab therapy, including 10 responders and 10 nonresponders, indicated that ECM deposition in liver metastases and a highly activated fatty acid oxidation (FAO) pathway were elevated in nonresponders after antiangiogenic therapy compared with responders. In mouse models of liver metastatic colorectal cancer (mCRC), anti-VEGF increased ECM deposition and FAO in colorectal cancer cells, and treatment with the FAO inhibitor etomoxir enhanced the efficacy of antiangiogenic therapy. Hepatic stellate cells (HSC) were essential for matrix stiffness–mediated FAO in colon cancer cells. Matrix stiffness activated lipolysis in HSCs via the focal adhesion kinase (FAK)/yes-associated protein (YAP) pathway, and free fatty acids secreted by HSCs were absorbed as metabolic substrates and activated FAO in colon cancer cells. Suppressing HSC lipolysis using FAK and YAP inhibition enhanced the efficacy of anti-VEGF therapy. Together, these results indicate that bevacizumab-induced ECM remodeling triggers lipid metabolic cross-talk between colon cancer cells and HSCs. This metabolic mechanism of bevacizumab resistance mediated by the physical tumor microenvironment represents a potential therapeutic target for reversing drug resistance.

Significance:

Extracellular matrix stiffening drives bevacizumab resistance by stimulating hepatic stellate cells to provide fuel for mCRC cells in the liver, indicating a potential metabolism-based therapeutic strategy for overcoming resistance.
TABLE 3 from A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer
Authors: Nguyen Vina P. , Campbell Katie M. , Nowicki Theodore S. , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L. , Chang Helena R. , Oseguera Denise K. , Ribas Antoni , Glaspy John A.
Published: August 2023

Tumor sizes, response to therapy, and follow-up events
Supplementary Table S2 from A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer
Authors: Nguyen Vina P. , Campbell Katie M. , Nowicki Theodore S. , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L. , Chang Helena R. , Oseguera Denise K. , Ribas Antoni , Glaspy John A.
Published: August 2023

Summary of antibodies, antigen retrieval conditions, incubation conditions, and opal dye labeling for multiplex immunofluorescence experiments
Supplementary Figure S2 from A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer
Authors: Nguyen Vina P. , Campbell Katie M. , Nowicki Theodore S. , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L. , Chang Helena R. , Oseguera Denise K. , Ribas Antoni , Glaspy John A.
Published: August 2023

Immune cell deconvolution of bulk RNA-seq data. MCPcounter was used to summarize gene expression scores for immune cell populations from bulk RNA-seq expression data across ten cell types. Each point represents one sample, and paired baseline/surgery samples are connected by a line. Individual patients and their responses are indicated by color and point shape.
Supplementary Figure S1 from A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer
Authors: Nguyen Vina P. , Campbell Katie M. , Nowicki Theodore S. , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L. , Chang Helena R. , Oseguera Denise K. , Ribas Antoni , Glaspy John A.
Published: August 2023

Surgical specimens after neoadjuvant therapy from patients who did not respond to treatment. Color scheme: Yellow: CD8, Red: IgG4, White: CK7, Green: PD-L1, Magenta: PD-1, Blue: DAPI. Staining demonstrates minor CD8 T-cell infiltration within viable tumor tissue, with no detectable PD-1, PD-L1, or IgG4 signal present.
Data from A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer
Authors: Nguyen Vina P. , Campbell Katie M. , Nowicki Theodore S. , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L. , Chang Helena R. , Oseguera Denise K. , Ribas Antoni , Glaspy John A.
Published: August 2023

Purpose:
Neoadjuvant combination immune checkpoint blockade and intralesional oncolytic virotherapy have the potential to activate antitumor responses in patients with breast cancer.
Experimental Design:
Eligibility for this pilot phase I trial included patients with localized HER2-negative breast cancer who received systemic nivolumab and ipilimumab and intratumor talimogene laherparepvec (T-VEC; NCT04185311). The primary objective was to evaluate the safety and adverse event profile of immunotherapy combined with T-VEC in patients with localized, HER2-negative breast cancer.
Results:
Six patients were enrolled, 4 having relapses after prior neoadjuvant chemotherapy and 2 who were previously untreated. Toxicities included 1 patient having grade 3 hypotension and type 1 diabetes mellitus, 3 patients with hypothyroidism, and all patients having constitutional symptoms known to be associated with the administration of T-VEC. One patient had a pathologic complete response, 3 patients had pathologic partial responses, 1 showed no significant response, and 1 had disease progression. Biopsies demonstrated increased immune cell infiltration in samples from patients who responded to therapy.
Conclusions:
This triple immunotherapy regimen provided responses in patients with advanced or relapsed HER2-negative breast cancer, at the expense of long-term toxicities.
Significance:
Systemic immune checkpoint blockade with a programmed death receptor 1 and a CTL antigen-4 blocking antibody, combined with intralesional oncolytic virotherapy, is a chemotherapy-free combination aimed at inducing an antitumor immune response locally and systemic immunity.
O Bildungsroman na concepção emancipatória do sujeito judeu colonizado na obra de Albert Memmi
Authors: Barbosa Daiani da Silva
Published: August 2023

O presente artigo analisa a obra A estátua de sal, do escritor franco-tunisiano Albert Memmi em diálogo com a teoria sobre o Bildungsroman, entendido como “romance de formação”, e o campo dos Estudos Culturais. Desse modo, inserimos a obra neste gênero literário mas, ao mesmo tempo, a apresentamos como uma subversão dos modelos clássicos ao desviar a trajetória do herói do enredo padrão em obras paradigmáticas de autoformação. Assim, além da formação da personalidade do sujeito, discutiremos a herança judaica do personagem e sua condição de colonizado pelo império francês, bem como a relação tradição-modernidade no contexto neocolonial do século XX.
Racial and Ethnic Disparities in Treatment of Critical Limb Ischemia: A National Perspective
Authors: Wahood Waseem , Duval Sue , Takahashi Edwin A. , Secemsky Eric A. , Misra Sanjay
Published: August 2023

Background

Recent guidelines have emphasized the use of medical management, early diagnosis, and a multidisciplinary team to effectively treat patients with critical limb ischemia (CLI). Previous literature briefly highlighted the current racial disparities in its intervention. Herein, we analyze the trend over a 14‐year time period to investigate whether the disparities gap in CLI management is closing.

Methods and Results

The National Inpatient Sample was queried between 2005 and 2018 for hospitalizations involving CLI. Nontraumatic amputations and revascularization were identified. Utilization trends of these procedures were compared between races (White, Black, Hispanic, Asian and Pacific Islander, Native American, and Other). Multivariable regression assessed differences in race regarding procedure usage. There were 6 904 562 admissions involving CLI in the 14‐year study period. The rate of admissions in White patients who received any revascularization decreased by 0.23% (
P
<0.001) and decreased by 0.25% (
P
=0.025) for Asian and Pacific Islander patients. Among all patients, the annual rate of admission in White patients who received any amputation increased by 0.21% (
P
<0.001), increased by 0.19% (
P
=0.001) for Hispanic patients, and increased by 0.19% (
P
=0.012) for the Other race patients. Admissions involving Black, Hispanic, Asian and Pacific Islander, or Other race patients had higher odds of receiving any revascularization compared with White patients. All races had higher odds of receiving major amputation compared with White patients.

Conclusions

Our analysis highlights disparities in CLI treatment in our nationally representative sample. Non‐White patients are more likely to receive invasive treatments, including major amputations and revascularization for CLI, compared with White patients.
Association of a Healthy Lifestyle, Life's Essential 8 Scores With Incident Macrovascular and Microvascular Disease Among Individuals With Type 2 Diabetes
Authors: He Panpan , Li Huan , Ye Ziliang , Liu Mengyi , Zhou Chun , Wu Qimeng , Zhang Yanjun , Yang Sisi , Zhang Yuanyuan , Qin Xianhui
Published: August 2023

Background

The association of a healthy lifestyle with the prognosis of type 2 diabetes remains uncertain. We aimed to evaluate the associations of a healthy lifestyle and a higher American Heart Association's Life's Essential 8 score with incident macrovascular and microvascular diseases in type 2 diabetes.

Methods and Results

A total of 13 543 participants with baseline type 2 diabetes and free of macrovascular and microvascular diseases from the UK Biobank were included. A healthy lifestyle was determined based on body mass index, smoking, alcohol consumption, physical activity, sleep duration, and diet. Life's Essential 8 scores were generated from 8 metrics according to the American Heart Association's cardiovascular health advisory, ranging from 0 to 100. During a median follow‐up of 12.1 years, 3279 (24.2%) incident macrovascular diseases and 2557 (18.9%) microvascular diseases were documented. Compared with those with a poor lifestyle, participants with an ideal lifestyle had significantly lower risks of incident macrovascular disease (hazard ratio [HR], 0.46 [95% CI, 0.36–0.59]) and microvascular disease (HR, 0.60 [95% CI, 0.47–0.77]). Significantly lower risks of macrovascular disease (HR, 0.20 [95% CI, 0.05‐0.79]) and microvascular disease (HR, 0.24 [95% CI, 0.06‐0.98]) were also found in the high cardiovascular health group (Life's Essential 8 scores: 80–100), compared to the low cardiovascular health group (scores: 0–49). Adhering to an ideal lifestyle may prevent 37.0% of macrovascular disease and 24.7% of microvascular disease, and attaining a high cardiovascular health may prevent 71.9% of macrovascular disease and 67.5% of microvascular disease.

Conclusions

A healthy lifestyle and a higher Life's Essential 8 score were associated with lower risks of macrovascular and microvascular diseases among participants with type 2 diabetes.
Judging Abstract Expressionist and Conceptual Artworks under Different Information Conditions
Authors: Gonzalez Federico M. , Burin Débora I.
Published: August 2023

Verbal information presented alongside artworks affects how they are judged and experienced, with diverse effects depending on aspects like information type and artistic style. The aim of the present studies was to explore the effect of different types of information (image only, short label, descriptive text, and interpretive text) on a range of responses to abstract expressionist and conceptual artworks, including aesthetic and epistemic emotions, judgments of understanding, and artistic value. Interpretive texts had positive effects on appraised ability to understand, epistemic emotions, and artistic value judgments, while descriptive texts affected aesthetic emotions. Artistic style was only relevant for the effect on epistemic emotions. Additionally, viewing times were shorter for images presented after texts. Overall, results suggest that different types of information might relate to different facets of the aesthetic experience.
9. From Turing’s Speculations to an Academic Discipline: A History of AI Existential Safety
Authors: Burden John , Clarke Sam , Whittlestone Jess
Published: August 2023

Through a short history of research into artificial intelligence, this chapter emphasises the need to ensure the safety of such technology. From longstanding fears of hubris to contemporary technical challenges, concerns around this modern technology are discussed, and the need to make progress on AI existential safety to avoid dangers to future generations is scrutinised.
Foreword
Authors: Anderson Terry
Published: August 2023

This collection of reflective essays is a treasure trove of advice, reflection and hard-won experience from experts in the field of open and distance education. Each chapter offers tried-and-tested advice for nascent academic writers, delivered with personal, rich, and wonderful stories of the authors’ careers, their process, their research and their writing, and the struggles and triumphs they have encountered in the course of their careers.
Effects of Computer Virtual Screening and Treatment Based on Pharmacophore BRD4-Targeted Small-Molecule Inhibitors on NSE and CA19-9 Levels in Patients with Liver Cancer
Authors: Wang Ying , Wang Hongwei , Liang Li , Jia Chongyang
Published: August 2023

Objective: Neuron-specific enolase (NSE) and carbohydrate antigen 19-9 (CA19-9) levels were compared before and after treatment with brd4-targeting small-molecule inhibitors based on pharmacophores and computer technology to investigate an efficient virtual screening method for
bromodomain protein 4 (brd4)-targeted small-molecule inhibitors. The purpose of this research was to examine the efficacy of pharmacophore screening and BRD4 targeting by small-molecule inhibitors in the management of liver cancer. Methods: Subjects included 106 individuals with hepatocellular
cancer who were hospitalised between July 2019 and December 2021. Using a receiver operating characteristic (ROC) curve, we assessed the clinical relevance and utility of pharmacophore-based virtual screening for brd4-targeted small-molecule inhibitors. The levels of the tumour markers NSE
and CA19-9 were analysed for changes using computational methods. Results: The pharmacophore model was built using the HipHop technique, and its results were validated and optimised utilising computational technology analysis. Twenty-four small-molecule classes were covered by the pharmacophore,
and the number of mismatched pharmacodynamic characteristics was 0. The first eight pharmacophores each had two clusters of hydrophobic atoms, a hydrogen bond receptor, and an aromatic ring at its core. There were no changes to the pharmacodynamic characteristics, although their locations
varied. False-positive and true-positive rates are depicted on the horizontal and vertical axes, respectively, in the figure below; the other two pharmacophore groups contained a hydrophobic cluster, a hydrogen bond receptor, and the centre of an aromatic ring. The ROC curve was quite consistent,
as indicated by an AUC value close to 1, which was between 0 and 1. For pharmacophores 07 and 06, the area under the curve (AUC) was 0.949 and 0.955, respectively, very near to 1. Both the hydrophobic cluster and the hydrogen bond receptor are required for a pharmacophore to exist. The examination
of pharmacodynamic definitions revealed a positive correlation between database reliability and element type (P <0.05). Compared to pre-healing levels, post-healing CA19-9 and NSE levels were statistically considerably reduced (P < 0.05). Conclusions: The assessment
approach was highly accurate and specific, and the pharmacophore-based virtual screening method and computer technology for brd4-targeting small-molecule inhibitors were of great benefit in the regulation of the cell cycle and the process of cell proliferation. Effective treatment modalities
can be created to increase levels of tumour markers NSE and CA19-9, and pharmacophore and computational-based small-molecule inhibitors of brd4 can be employed as crucial virtual screening criteria for the evaluation of liver cancer.
High Ribonucleotide Reductase M2 Expression as an Independent Prognostic Biomarker and Correlated with Immune Infiltrates in Live Hepatocellular Carcinoma
Authors: Zheng Yukun , Wang Xiaoyi , Wang Xiaoliang
Published: August 2023

Hepatocellular carcinoma (LIHC) is a prevalent cancer worldwide. High expression of Ribonucleotide reductase M2 (RRM2), a gene expressed in various tumors including LIHC, has been associated with poor prognosis, yet its correlation with immune cell infiltration in LIHC remains unclear.
We aimed to develop a prognosis model for patient prognosis analysis and immunotherapy using RRM2 expression data and corresponding clinical data collected from The Cancer Genome Atlas (TCGA) database. Patients were divided into high- and low-risk groups based on their median risk score. Our
analysis revealed that high expression of RRM2 was associated with T-stage, pathological stage, histologic grade, AFP levels, and age. Further analysis showed that cell cycle checkpoints, B cell receptor, cell cycle, MHC class II antigen, cancer pathway, and TP53 were differentially enriched
in the RRM2 high expression phenotype. Additionally, RRM2 correlated with the majority of immune cell infiltration levels and was positively correlated with Th2 cells and negatively correlated with neutrophil cells, DC, CD8 T cells, and NK cells. The levels of these immune cells were significantly
different between the RRM2 high and low expression groups. Our study suggests that overexpression of RRM2 is associated with poor prognosis in LIHC and may represent a valuable prognostic biomarker for this cancer.
FTO-Mediated lncRNA-FNDRR Axis Demethylation Promotes Cell Proliferation, Invasion, and Migration in Esophageal Squamous Cell Carcinoma
Authors: Liang Xuyang , Wang Libo , Wang Lu , Zhang Shuxian , Ren Ling , Li Shouying , Xu Jing , Xu Ping
Published: August 2023

Esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and has a significant impact on patient survival and quality of life. The role of N6-methyladenosine (m6A) modification in the regulation of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) has been
reported in various diseases, including cancer. Although the clinical value of lncRNA-FNDRR in predicting ESCC prognosis is well-established, its molecular mechanism in ESCC remains incompletely understood. Therefore, in this study, we aimed to investigate the involvement of the m6A-lncRNA-FNDRR
axis in ESCC progression. Results revealed that overexpression of lncRNA-FNDRR exerted inhibitory effects on ESCC cell proliferation, migration, and invasion. Interestingly, knockdown of the demethylase enzyme fat mass and obesity-associated protein (FTO) resulted in similar effects to those
achieved by overexpressing lncRNA-FNDRR in ESCC cells. Moreover, we found that FTO had the ability to reverse the m6A modification of lncRNA-FNDRR. Importantly, simultaneous knockdown of FTO and overexpression of lncRNA-FNDRR promoted ESCC cell proliferation and metastasis, suggesting a synergistic
effect between these two factors. These results provide valuable insights into the molecular mechanisms underlying ESCC and highlight the significance of m6A modifications in this context. Further investigations on m6A modifications in ESCC are warranted to deepen our understanding of this
disease and explore potential therapeutic strategies.
Investigation of Breakdown in Vertical E-Mode Ga2O3 MOSFET with Different Structural Parameters
Authors: Li Xuanlin , Liu Weijing , Li Qinghua
Published: August 2023

In order to control drain-induced barrier lowering (DIBL) and thus premature breakdown in enhancement-mode (E-mode) Ga2O3 MOSFETs, the effect of structure and process parameters on the breakdown voltage (VBK) and DIBL is systematically investigated.
The results show that the small gate work function, the small oxide dielectric constant, the thick oxide thickness, the excessive doping concentration of the epitaxial layer, and the wide and short channel will lead to a severe DIBL effect, causing the device to breakdown prematurely. On the
other hand, the thickness of the drift region has a marginal effect on the DIBL, and after excluding other structural parameters that generate a strong DIBL effect, a reasonable increase in the thickness of the drift region is beneficial to improve the VBK of devices. This study
can contribute to the design of Ga2O3 MOSFETs in the application scenario with high VBK reliability requirements.
4T Complementary Metal Oxide Semiconductor Image Sensor Charge Transfer Efficiency Optimization
Authors: Zhang Kai , Li Ting , Xu Weidong , He Jie , Li Haisong
Published: August 2023

4T CMOS image sensors are widely used in various imaging fields by virtue of low noise, high integration and low cost, but their pixel cells are manufactured with non-ideal effects causing trap energy levels and potential deviations, resulting in incomplete charge transfer of photogenerated
signals, thus producing image trailing and affecting the imaging effect. Traditionally, the improvement of charge transfer efficiency is only limited to the optimization of one or two parameters or the optimization of the working state. In this paper, we propose a more systematic research
method to optimize the charge transfer efficiency through five aspects: TG channel threshold voltage injection adjustment, PPD N-type impurity injection dose and injection angle, as well as TG operating voltage and FD reset voltage, respectively. The optimal process state and operating
conditions are obtained: TG channel injection dose of 8.0 e12 cm−2, PPD N-type impurity injection dose of 3.0 e12 cm−2, injection angle of −4°, TG operating voltage of 2.7 V and FD reset voltage of 3.9 V, where the residual
charge in the signal transfer path is minimal, and the design method in this paper has some guidance for the design of CIS pixels.
Cytotoxic Activity of Vitex leucoxylon Aqueous Leaf Extract Against A549 and NCIH-460 Lung Cancer Cell Lines
Authors: Shaikh Ibrahim Ahmed , Nasreen Aayesha , Mahnashi Mater H. , Hoskeri Joy H. , Shettar Arun K. , Mannasaheb Basheerahmed Abdulaziz , Ghoneim Mohammed M. , Asdaq Syed Mohammed Basheeruddin , Muddapur Uday M. , Khan Aejaz Abdullatif , Dafalla Salah Eldeen , Mohammed Tasneem
Published: August 2023

The primary goal of this research was to determine the cytotoxic potential of an aqueous extract of Vitex leucoxylon aerial parts on the lung cancer A549 and non-small cell lung cancer NCIH-460 cell lines. The Soxhlet apparatus and distilled water were used for the extraction
of the medicinal plant. The MTT in vitro assay was used to test the compounds for anticancer activity against two different lines of lung cancer. The cytotoxic activity of V. leucoxylon in the present study was very substantial as measured by its ability to suppress the growth
of both cell lines. The IC50 values for A549 and NCI-H460 were determined to be 315.57 and 560.48 μg/mL, respectively. The current research confirmed that V. leucoxylon’s aqueous leaf extract possessed potent anticancer properties. Both the cancer cell lines
were significantly inhibited in their ability to differentiate when subjected to the MTT assay. In future, flavonoid compounds in the aqueous extract need to be purified, characterized, and structurally elucidated for in-vivo studies, which could lead to the creation of new drug candidates.
Preparation of Morphologically and Dimensionally Controlled MIL-53(Al)
Authors: Chen Lin , Zhang Hang , Fouad Hassan , Akhtar M. S. , Wang Zhihong
Published: August 2023

This study presents a straightforward hydrothermal synthesis technique for modifying the crystal size and shape of MIL-53(Al) via the use of a mixed solvent solution consisting of water and DMF. Without the use of coordination inhibitors or surfactants, a sequence of nanosized MIL-53(Al)
crystals was efficiently synthesized. The lowest crystal size we were able to achieve in this work was 100 nm, but present technologies are not suited to creating nanoscale crystals of this size. Large crystallinity and yield were attained, and the samples’ very large specific surface
areas expanded the usefulness of this MOF material for gas adsorption and storage. X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, nitrogen gas adsorption/desorption, and infrared spectroscopy were all used to characterize the samples. Finally, the effect of moisture
concentration on crystal size and shape was investigated.
The Role of PRMT7 and KLF4 in Driving the Malignant Progression of Gastric Cancer
Authors: Dong Peng , Liu Meng , Feng Yanfei , Bi Xiaochen
Published: August 2023

This study investigates the impact of PRMT7 on the malignant behaviors of gastric cancer (GC) and explores its potential as a therapeutic target for GC treatment. Clinical specimens and cytological experiments were analyzed to assess the effects of PRMT7. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure relative levels of PRMT7 in 48 pairs of GC and adjacent normal tissues. The influence of PRMT7 on clinical features and prognosis in GC patients was examined. The regulatory effects of PRMT7 on proliferative and migratory potentials in GC cells were evaluated using cell counting kit-8 (CCK-8) and transwell assay, respectively. Additionally, the role of PRMT7 and its downstream target in regulating malignant behaviors of GC was elucidated. Results showed that PRMT7 was upregulated in GC tissues, and its high expression in GC patients was associated with tumor staging and lymphatic metastasis, indicating a poor prognosis. PRMT7 stimulated proliferative and migratory potentials in GC cells, and KLF4 was identified as the downstream gene of PRMT7 responsible for the PRMT7-mediated malignant phenotypes of GC. In conclusion, PRMT7 is upregulated in GC tissues and its elevated levels are closely linked to tumor staging and lymphatic metastasis, predicting an unfavorable prognosis. PRMT7 drives the proliferative and migratory potentials of GC cells through the negative regulation of KLF4. The findings suggest that PRMT7 could be a potential therapeutic target for GC.
Ultrasonic Velocity, Viscosity and Thermal Conductivity Studies on Barium Oxide: Silicone Oil Nanofluids
Authors: Prakash P. , Jeevaraj A. Kingson Solomon , Mahmoud Mohamed H. , Akhtar M. S. , Altinawi Amir
Published: August 2023

In this study, we focused on the preparation and characterization of Barium oxide (BaO): Silicone oil nanofluids with the assistance of ultrasonication. The purpose was to investigate the potential impact of these nanofluids on solar radiation absorption. To achieve this, six different concentrations (ranging from 0.01 g to 0.06 g) of BaO: Silicone oil nanofluids were prepared. The nanofluids were subjected to various characterization techniques to evaluate their properties. Ultrasonic velocity measurements were conducted to assess the dispersion quality and stability of the nanofluids. Fourier transform infrared (FTIR) spectroscopy was utilized to examine any potential interactions between the nanoparticles and the fluid medium. Ultraviolet-Visible (UV-Visible) spectroscopy was employed to investigate the optical properties of the nanofluids, particularly their ability to absorb solar radiation. Additionally, electron microscopy analysis provided insights into the morphology and size distribution of the BaO nanoparticles. The results obtained from the UV-Visible analysis provided valuable information regarding the solar radiation absorption efficiency of the BaO: Silicone oil nanofluid systems. These findings contribute to our understanding of the potential application of these nanofluids in solar energy harvesting. Furthermore, the ultrasonic studies and FTIR analysis confirmed that there were no significant particle-fluid interactions, indicating the stability of the nanofluids. Thermal conductivity measurements were carried out to determine the heat transfer efficiency of the BaO: Silicone oil nanofluid system at different concentrations. The results revealed an optimal concentration that exhibited the highest heat transfer efficiency, suggesting the potential of these nanofluids for enhancing heat transfer processes. In conclusion, this study successfully prepared and characterized BaO: Silicone oil nanofluids. The analysis of their optical properties, stability, and thermal conductivity provides valuable insights into their potential application in solar radiation absorption and heat transfer systems. Further research can explore the practical implementation of these nanofluids in solar energy conversion and thermal management technologies.
Verif: A Weather-Prediction Verification Tool for Effective Product Development
Authors: Nipen Thomas N. , Stull Roland B. , Lussana Cristian , Seierstad Ivar A.
Published: August 2023

Verif is an open-source tool for verifying weather predictions against a ground truth. It is suitable for a range of applications and designed for iterative product development involving fine-tuning of algorithms, comparing methods, and addressing scientific issues with the product. The tool generates verification plots based on user-supplied input files containing predictions and observations for multiple point-locations, forecast lead times, and forecast initialization times. It supports over 90 verification metrics and diagrams and can evaluate deterministic and probabilistic predictions. An extensive set of command-line flags control how the input data are aggregated, filtered, stratified, and visualized. The broad range of metrics and data manipulation options allows the user to gain insight from both summary scores and detailed time series of individual weather events. Verif is suitable for many applications, including assessing numerical weather prediction models, climate models, reanalyses, machine learning models, and even the fidelity of emerging observational sources. The tool has matured through long-term development at the Norwegian Meteorological Institute and the University of British Columbia. Verif comes with an extensive wiki page and example input files covering a wide range of prediction applications, allowing students and researchers interested in verification to get hands-on experience with real-life datasets. This article describes the functionality of Verif version 1.3 and shows how the tool can be used for effective product development.
MJO Influence on Subseasonal-to-Seasonal Prediction in the Northern Hemisphere Extratropics
Authors: Kim Hera , Son Seok-Woo , Kim Hyemi , Seo Kyong-Hwan , Kang Min-Jee
Published: August 2023

The impacts of the Madden–Julian oscillation (MJO) on the subseasonal-to-seasonal (S2S) prediction in the Northern Hemisphere extratropics are examined using the reforecasts from the S2S Project and Subseasonal Experiment Project (SubX). When forecasts are initialized during an active MJO, extratropical prediction skill becomes significantly higher at 3–4-week windows compared to inactive MJO. Such prediction skill improvement is evident in the 500-hPa geopotential height over the Pacific–North America region and the North Atlantic and in surface temperature over North America, especially when the model is initialized during the MJO phases 6–7 and 8–1. However, the extratropical prediction skill is not modulated by the MJO phases 2–3 and 4–5. This phase dependency is likely determined by the arrival time of the MJO at the Maritime Continent (MC) barrier that substantially enhances the MJO amplitude error. This result suggests that only MJO phases whose convection lies east of the MC are a source of wintertime S2S predictability in the extratropics.
Using a Reanalysis-Driven Land Surface Model for Initialization of a Numerical Weather Prediction System
Authors: Bakketun Åsmund , Blyverket Jostein , Müller Malte
Published: August 2023

Realistic initialization of the land surface is important to produce accurate NWP forecasts. Therefore, making use of available observations is essential when estimating the surface state. In this work, sequential land surface data assimilation of soil variables is replaced with an offline cycling method. To obtain the best possible initial state for the lower boundary of the NWP system, the land surface model is rerun between forecasts with an analyzed atmospheric forcing. We found a relative reduction of 2-m temperature root-mean-square errors and mean errors of 6% and 12%, respectively, and 4.5% and 11% for 2-m specific humidity. During a convective event, the system was able to produce useful (fractions skill score greater than the uniform forecast) forecasts [above 30 mm (12 h)−1] down to a 100-km length scale where the reference failed to do so below 200 km. The different precipitation forcing caused differences in soil moisture fields that persisted for several weeks and consequently impacted the surface fluxes of heat and moisture and the forecasts of screen level parameters. The experiments also indicate diurnal- and weather-dependent variations of the forecast errors that give valuable insight on the role of initial land surface conditions and the land–atmosphere interactions in southern Scandinavia.
Exchange of Extracorporeal Membrane Oxygenation Cannulas for Hemodialysis Catheters in Children Requiring Renal Replacement Therapy
Authors: Cruz-Centeno Nelimar , Stewart Shai , Marlor Derek R. , Rivard Douglas C. , Daniel John M. , Oyetunji Tolulope A. , Hendrickson Richard J.
Published: August 2023

Background

Pediatric patients requiring extracorporeal membrane oxygenation (ECMO) may require renal replacement therapy even after decannulation. However, data regarding transition from ECMO cannulation to a hemodialysis catheter in pediatric patients is not currently available.

Methods

Patients <18 years old who had an ECMO cannula exchanged for a hemodialysis catheter during decannulation at a tertiary care children’s center from January 2011 to September 2022 were identified. Data was collected from the electronic medical record.

Results

A total of 10 patients were included. The cohort was predominantly male (80.0%, n = 8) with a median age of 1 day (IQR 1.0, 24.0). All ECMO cannulations were veno-arterial in the right common carotid artery and internal jugular vein. The median time on ECMO was 8.5 days (IQR 6.0, 15.0). One patient had the venous cannula exchanged for a tunneled hemodialysis catheter during decannulation, two were transitioned to peritoneal dialysis, and seven had the temporary hemodialysis catheter converted to a tunneled catheter by Interventional Radiology (when permanent access was required) at a median time of 10 days (IQR 8.0, 12.5). Of these 7 patients, 28.6% (n = 2) developed catheter-associated infection within 30 days of replacement, with one requiring catheter replacement. Transient bloodstream infection occurred in 10.0% (n = 1) within 30 days of ECMO cannula exchange.

Conclusion

Venous ECMO cannula exchange for a hemodialysis catheter in children requiring renal replacement therapy after decannulation is possible as a bridge to a permanent hemodialysis or peritoneal catheter if renal function does not recover, while supporting vein preservation.