bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and assessment of new PIM2 inhibitors for treating hematologic cancers: A combined approach of energy‐based virtual screening and machine learning evaluation
Authors: Chen Xi , Zhao Jingyi , Chen Roufen , Shen Liteng , Lu Jialiang , Guo Yu , Chi Xinglong , Geng Shuangshuang , Zhang Qingnan , Pan Zhichao , He Xinjun , Xu Lei , Shen Zheyuan , Yang Haiyan , Lei Tao 
Published: January 2024

AbstractPIM2, part of the PIM kinase family along with PIM1 and PIM3, is often overexpressed in hematologic cancers, fueling tumor growth. Despite its significance, there are no approved drugs targeting it. In response to this challenge, we devised a thorough virtual screening workflow for discovering novel PIM2 inhibitors. Our process includes molecular docking and diverse scoring methods like molecular mechanics generalized born surface area, XGBOOST, and DeepDock to rank potential inhibitors by binding affinities and interaction potential. Ten compounds were selected and subjected to an adequate evaluation of their biological activity. Compound 2 emerged as the most potent inhibitor with an IC50 of approximately 135.7 nM. It also displayed significant activity against various hematological cancers, including acute myeloid leukemia, mantle cell lymphoma, and anaplastic large cell lymphoma (ALCL). Molecular dynamics simulations elucidated the binding mode of compound 2 with PIM2, offering insights for drug development. These results highlight the reliability and efficacy of our virtual screening workflow, promising new drugs for hematologic cancers, notably ALCL.
How hermeneutics can guide grading in integrated STEAM education: An evidence‐informed perspective
Authors: DeLuca Christopher , Dubek Michelle , Rickey Nathan 
Published: January 2024

AbstractAddressing calls to develop assessment theories for integrated teaching and learning, we propose an evidence‐informed perspective on grading in Science, Technology, Engineering, Arts and Mathematics (STEAM) education. We leveraged a qualitative collective case study design to generate rich profiles of three exemplary STEAM teachers' grading approaches and practices. Data sources included semi‐structured interviews and artefacts of teachers' instruction and assessment practice. We analysed qualitative data from interviews and artefacts using a general inductive approach. The teachers in our study pushed back against ‘objective’ views of grading, whereby grades are composites of summative assessments, in favour of informed and contextualised grading, which aims to document and support a negotiated understanding of each student's learning journey. Teachers' grading practices aligned with a hermeneutic approach to classroom assessment validity: the teachers (a) collected and interpreted a wide range of evidence of student (re)learning; (b) centred students' perspectives and evidences; and (c) employed their professional judgement to determine students' grades. Teachers characterised grading as a process of accounting for all available evidence, blurring the boundaries between formative and summative assessment. Documenting the learning process, rather than focusing on products, can support deeply integrated learning. Importantly, the teachers supported students in documenting their own learning and negotiating their grades with reference to self‐generated evidence. This practice stands to reduce power imbalances between students and teachers and foster students' self‐regulated learning. Our findings inform a framework which STEAM educators can use to guide grading in integrated classrooms, an enduring challenge for integrated learning.
A novel experimental method to determine substrate uptake kinetics of gaseous substrates applied to the carbon monoxide‐fermenting Clostridium autoethanogenum
Authors: Allaart Maximilienne T. , Korkontzelos Charilaos , Sousa Diana Z. , Kleerebezem Robbert 
Published: January 2024

AbstractSyngas fermentation has gained momentum over the last decades. The cost‐efficient design of industrial‐scale bioprocesses is highly dependent on quantitative microbial growth data. Kinetic and stoichiometric models for syngas‐converting microbes exist, but accurate experimental validation of the derived parameters is lacking. Here, we describe a novel experimental approach for measuring substrate uptake kinetics of gas‐fermenting microbes using the model microorganism Clostridium autoethanogenum. One‐hour disturbances of a steady‐state chemostat bioreactor with increased CO partial pressures (up to 1.2 bar) allowed for measurement of biomass‐specific CO uptake‐ and CO2 production rates (, ) using off‐gas analysis. At a pCO of 1.2 bar, a of −119 ± 1 mmol g−1X h−1 was measured. This value is 1.8–3.5‐fold higher than previously reported experimental and kinetic modeling results for syngas fermenters. Analysis of the catabolic flux distribution reveals a metabolic shift towards ethanol production at the expense of acetate at pCO  0.6 atm, likely to be mediated by acetate availability and cellular redox state. We characterized this metabolic shift as acetogenic overflow metabolism. These results provide key mechanistic understanding of the factors steering the product spectrum of CO fermentation in C. autoethanogenum and emphasize the importance of dedicated experimental validation of kinetic parameters.
Corporate digitalization and green innovation: Evidence from textual analysis of firm annual reports and corporate green patent data in China
Authors: Fang Liting , Li Zhaohua 
Published: January 2024

AbstractWe investigate the effect of corporate digitalization capabilities on green innovation among Chinese‐listed firms. Using a panel dataset of 2908 companies from 2011 to 2020, we use textual analysis and entropy weighting on corporate annual reports to construct a yearly corporate digitalization index. Our findings show that corporate digitalization promotes green innovation, as evidenced by patent applications and grants. This relationship is stronger for firms with fewer financial constraints and in provinces with strong intellectual property protection. We also find the national digital policy of the “Internet Plus” strategy has a stronger positive effect on corporate green innovation for corporations with a higher degree of digitalization. Our results are robust to various alternative measures, econometric models, and different samples.
Exploring the potential of blockchain‐enabled smart contracts for achieving net‐zero emissions: An empirical study
Authors: Bag Surajit , Rahman Muhammad Sabbir , Routray Susmi , Shrivastav Santosh Kumar , Agrawal Soni 
Published: January 2024

AbstractA sustainable future entails addressing net‐zero emissions, which balances greenhouse gas emissions, thereby mitigating climate change. This study explores the relationship between the information quality, system quality, and service quality of blockchain‐enabled smart contracts (BSCs) with collaboration quality to achieve net‐zero emissions. The study further explores the role of collaboration quality in influencing the intention‐to‐use BSC and organizational satisfaction. The study employed the revised DeLone and McLean model and validated it with data from 434 respondents using structural equation modeling. The results validate all the hypotheses derived from the updated DeLone and McLean information system (IS) success model. There exist significant relationships between information quality, system quality, and service quality in the BSCs leading to collaboration quality to achieve net‐zero emissions. The study establishes the significant role of collaboration quality which positively impacts usage behavior and organizational satisfaction, mediated by the intention to use. The findings of this study offer insights for organizations and policymakers seeking to harness blockchain for environmental sustainability.
Chemometrics‐based Chemical Analysis of Myrrh and Its Vinegar‐processed Products by UPLC‐MS/MS
Authors: Wang Yuan , Li Na , Rao Jinqiu , Wang Tianwang , Li Wei , Ren Xiaoliang , Wang Kai , Qiu Feng 
Published: January 2024

AbstractMyrrh is widely used in clinical practice but accompanied by obvious toxicity. According to traditional Chinese medicines theory, processing with vinegar can effectively reduce its toxicity. However, the detoxification processing technology of Myrrh and the corresponding mechanism have been unclear. The objective of this study is to systematically analyze the variation in chemical composition of raw Myrrh and its processed products using UPLC‐Q‐TOF‐MS/MS coupled with chemometrics. A total of 75 compounds including 56 sesquiterpenoids, 2 diterpenoids, 15 triterpenoids and 2 other types were identified. Raw Myrrh and its processed products were divided into two major groups, and 14 chemical markers were selected out by principal component analysis and partial least square discriminant analysis. Additionally, the exact content of 5 representative chemical markers was determined to be significantly reduced after vinegar‐processing by UPLC‐QQQ‐MS/MS. Moreover, multivariate statistical analysis and the quantitative results comprehensively indicated that the optimized processing method was processing at a ratio of 200 : 5 (Myrrh:vinegar). This research provides not only a reliable foundation for the study of Myrrh, but also a scientific reference for clinical use of this herb.
Development of Novel Indazolyl‐Acyl Hydrazones as Antioxidant and Anticancer Agents that Target VEGFR‐2 in Human Breast Cancer Cells
Authors: Parameshwaraiah Sindhu M. , Shivakumar Rashmi , Xi Zhang , Siddappa Tejaswini P. , Ravish Akshay , Mohan Arunkumar , Poonacha Lisha K. , Uppar Pradeep M. , Basappa Shreeja , Dukanya Dukanya , Gaonkar Santhosh L. , Kemparaju Kempaiah , Lobie Peter E. , Pandey Vijay , Basappa Basappa 
Published: January 2024

AbstractThe increased expression of VEGFR‐2 in a variety of cancer cells promotes a cascade of cellular responses that improve cell survival, growth, and proliferation. Heterocycles are common structural elements in medicinal chemistry and commercially available medications that target several biological pathways and induce cell death in cancer cells. Herein, the evaluation of indazolyl‐acyl hydrazones as antioxidant and anticancer agents is reported. Compounds 4e and 4j showed inhibitory activity in free radical scavenging assays (DPPH and FRPA). The titled compounds were employed in cell viability studies using MCF‐7 cells, and it was observed that compounds 4f and 4j exhibited IC50 values 15.83 μM and 5.72 μM, respectively. In silico docking revealed the favorable binding energies of ‐7.30 kcal/mol and ‐8.04 kcal/mol for these compounds towards Vascular Endothelial Growth Factor Receptor‐2 (VEGFR‐2), respectively. In conclusion, compounds with antioxidant activity and that target VEGFR‐2 in breast cancer cells are reported.
What makes SARS‐CoV‐2 unique? Focusing on the spike protein
Authors: Qian Jingbo , Zhang Shichang , Wang Fang , Li Jinming , Zhang Jiexin 
Published: January 2024

AbstractSevere acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) seriously threatens public health and safety. Genetic variants determine the expression of SARS‐CoV‐2 structural proteins, which are associated with enhanced transmissibility, enhanced virulence, and immune escape. Vaccination is encouraged as a public health intervention, and different types of vaccines are used worldwide. However, new variants continue to emerge, especially the Omicron complex, and the neutralizing antibody responses are diminished significantly. In this review, we outlined the uniqueness of SARS‐CoV‐2 from three perspectives. First, we described the detailed structure of the spike (S) protein, which is highly susceptible to mutations and contributes to the distinct infection cycle of the virus. Second, we systematically summarized the immunoglobulin G epitopes of SARS‐CoV‐2 and highlighted the central role of the nonconserved regions of the S protein in adaptive immune escape. Third, we provided an overview of the vaccines targeting the S protein and discussed the impact of the nonconserved regions on vaccine effectiveness. The characterization and identification of the structure and genomic organization of SARS‐CoV‐2 will help elucidate its mechanisms of viral mutation and infection and provide a basis for the selection of optimal treatments. The leaps in advancements regarding improved diagnosis, targeted vaccines and therapeutic remedies provide sound evidence showing that scientific understanding, research, and technology evolved at the pace of the pandemic.
Overexpression of Fut 2, 4, and 8, and nuclear localization of Fut 4 in ovarian cancer cell lines induced by ascitic fluids from epithelial ovarian cancer patients
Authors: Alvear‐Hernandez Nayely Paulina , Hernández‐Ramírez Verónica Ivonne , Villegas‐Pineda Julio César , Osorio‐Trujillo Juan Carlos , Guzmán‐Mendoza José Jesús , Gallardo‐Rincón Dolores , Toledo‐Leyva Alfredo , Talamás‐Rohana Patricia 
Published: January 2024

AbstractFucosyltransferases (Fut) regulate the fucosylation process associated with tumorogenesis in different cancer types. Ascitic fluid (AF) from patients diagnosed with advanced stage of epithelial ovarian cancer (EOC) is considered as a dynamic tumor microenvironment associated with poor prognosis. Previous studies from our laboratory showed increased fucosylation in SKOV‐3 and OVCAR‐3, cancer‐derived cell lines, when these cells were incubated with AFs derived from patients diagnosed with EOC. In the present work we studied three fucosyltransferases (Fut 2, Fut 4, and Fut 8) in SKOV‐3, OVCAR‐3 and CAOV‐3 cell lines in combination with five different AFs from patients diagnosed with this disease, confirming that all tested AFs increased fucosylation. Then, we demonstrate that mRNAs of these three enzymes were overexpressed in the three cell lines under treatment with AFs. SKOV‐3 showed the higher overexpression of Fut 2, Fut 4, and Fut 8 in comparison with the control condition. We further confirmed, in the SKOV‐3 cell line, by endpoint PCR, WB, and confocal microscopy, that the three enzymes were overexpressed, being Fut 4 the most overexpressed enzyme compared to Fut 2 and Fut 8. These enzymes were concentrated in vesicular structures with a homogeneous distribution pattern throughout the cytoplasm. Moreover, we found that among the three enzymes, only Fut 4 was located inside the nuclei. The nuclear location of Fut 4 was confirmed for the three cell lines. These results allow to propose Fut 2, Fut 4, and Fut 8 as potential targets for EOC treatment or as diagnostic tools for this disease.
Awareness of the impact of sex and gender in the disease risk and outcomes in hematology and medical oncology—a survey of Swiss clinicians
Authors: Darphin Xenia , Moor Jeanne , da Silva Cristina Espinosa , Richters Anke , Özdemir Berna C. 
Published: January 2024

AbstractBackgroundAlthough male and female cancer patients are distinct in many ways, there is a limited understanding in the differences between male and female biology and differing pharmacokinetic responses to cancer drugs. In fact, sex and gender are currently not considered in most treatment decisions in the fields of oncology and hematology. The lack of knowledge about potential sex differences in both disciplines may lead to differences in treatment efficacy, toxicity, and the overall survival (OS) of patients.AimTo evaluate their awareness about sex and gender in clinical practice we surveyed Swiss hematologists and oncologists from September to November 2022.MethodsWe collected data about the clinical knowledge, experimental research, palliative care, quality of life, as well as the participant perception of the importance of sex and gender. We identified 767 eligible clinicians, of whom 150 completed the survey (20% response rate).ResultsWhile most participants agreed that sex and gender were relevant when treating patients, it became clear that fewer participants knew about sex and gender differences in treatment toxicity and survival, which in turn would affect the treatment of their patients. Most participants agreed that this topic should be integrated into continuing education and research.ConclusionOur findings indicate the need for more awareness and training on sex and gender in cancer research and clinical care among oncologists and hematologists. Ideally, by better educating medical students and health professionals, a demand is created for improving research policies, publications and therefore patient care.
DDoS attack detection in SDN: Enhancing entropy‐based detection with machine learning
Authors: Santos‐Neto Marcos J. , Bordim Jacir L. , Alchieri Eduardo A. P. , Ishikawa Edison 
Published: January 2024

SummarySoftware defined network (SDN) has emerged as a new paradigm in terms of network architecture, providing flexibility, agility, and programmability to network management. These benefits boosted the SDN adoption, bringing new challenges mainly related to security, in particular, those related to Denial of Service (DoS) and Distributed Denial of Service (DDoS) attacks. The detection, prevention, and mitigation of these attacks are important since they can affect the entire network. Many current security measures use statistical techniques, as entropy, or machine learning (ML) algorithms to detect DoS and DDoS attacks. While the definition of a threshold to determine whether a traffic is an attack is not trivial in statistical techniques, ML solutions may provide better accuracy but require considerable computational resources and time to converge to a model able to detect these attacks. Trying to circumvent these limitations, current hybrid approaches either use the results from entropy as input in ML algorithms (EntropyML) or use entropy as a filter and ML algorithms to identify attacks. This work goes one step ahead and combines these techniques in a three‐step approach (EntropyMLEntropy), called ML‐Entropy, which inherits the intelligence of ML algorithms to adjust the threshold used by entropy. The proposed solution was implemented and evaluated in two datasets, the well‐known synthetic DARPA dataset and a dataset composed by traffic collected from a real‐corporate environment. Experimental results show that, in general, ML‐Entropy presents an accuracy above 99%, similar to support vector machine (SVC) and random forest (RF) algorithms, being able to converge to a detection model up to and faster than RF and SVC, respectively.
Electron interaction with DNA constituents in aqueous phase
Authors: Parikh Smruti , Limbachiya Chetan 
Published: January 2024

AbstractElectron driven chemistry of biomolecules in aqueous phase presents the realistic picture to study molecular processes. In this study we have investigated the interactions of electrons with the DNA constituents in their aqueous phase in order to obtain the quantities useful for DNA damage assessment. We have computed the inelastic mean free path (IMFP), mass stopping power (MSP) and absorbed dose (D) for the DNA constituents (Adenine, Cytosine, Guanine, Thymine and Uracil) in the aqueous medium from ionisation threshold to 5000 eV. We have modified complex optical potential formalism to include band gap of the systems to calculate inelastic cross sections which are used to estimate these entities. This is the maiden attempt to report these important quantities for the aqueous DNA constituents. We have compared our results with available data in gas and other phase and have observed explicable accord for IMFP and MSP. Since these are the first results of absorbed dose (D) for these compounds, we have explored present results vis‐a‐vis dose absorption in water.
Affect trajectories surrounding binge eating episodes and heavy drinking episodes in adults with binge‐spectrum eating disorders
Authors: Wilkinson Megan L. , Manasse Stephanie M. , Juarascio Adrienne S. 
Published: January 2024

AbstractObjectiveThe comorbidity of binge eating and heavy drinking (BE + HD) is concerning due to high prevalence and associated consequences. Affective pathways may maintain BE + HD, yet more micro‐level research is needed. This study used ecological momentary assessment (EMA) to examine between‐person and day‐level relationships between positive and negative affect and binge eating or heavy drinking episodes in BE + HD.MethodsParticipants (N = 53) were adults with binge‐spectrum eating disorders who completed between 7 and 14 days of EMA prior to a treatment for binge eating.ResultsAnxiety was highest on days with both binge eating and heavy drinking, while excitement and confidence were highest on days with only heavy drinking episodes for BE + HD. Global negative affect was relatively stable surrounding binge eating episodes. Guilt significantly increased prior to binge eating, and sadness significantly decreased following binge eating. Global positive affect significantly decreased prior to and stopped decreasing following heavy drinking episodes.DiscussionResults support binge eating being negatively reinforced by specific aspects of negative affect, while heavy drinking may be positively reinforced by global positive affect for individuals with BE + HD. Clinicians should incorporate interventions that focus on specific negative affect dimensions and that promote alternative rewarding activities besides heavy drinking.
Telemedicine‐medical “snack community”‐PHS ecosystem: Insights into the double‐edged sword role of telemedicine in clinical practice and medical education during the COVID‐19 pandemic and beyond
Authors: Feng Dechao , Shi Xu , Wang Jie , Zhang Liying , Xiao Yuhan , Li Dengxiong , Wu Ruicheng , Wei Wuran , Miyamoto Akira , Yoo Koo Han , Ye Xing , Zhang Chi , Han Ping 
Published: January 2024

AbstractTelemedicine has gained tremendous development during the COVID‐19 pandemic. With deblocking and opening, telemedicine accelerates the evolvution of the medical “snack community” and undermines the perception of medical students and staff, which promotes the incidence of psychosocial‐related disorders. Moreover, the inconsistent telemedicine adaptability between medical workers and patients aggravates the doctor–patient conflict due to the aging population and COVID‐19 squeal. Telemedicine is colliding with the national healthcare system, whose synchronization with conventional medical service is crucial to coordinate the relationship among medical payment, patient privacy and qualifications of clinicians. This study puts more emphasis on the double‐edged sword role of telemedicine in clinical practice and medical education during the COVID‐19 pandemic and beyond. Overall, while telemedicine has demonstrated its utility in health care throughout the COVID pandemic, it is pretty critical to continue evaluating the efficacy and limitations of telemedicine in order to maintain equal access to medical service and high‐quality medical education. A new concept as telemedicine‐medical “snack community”‐PHS ecosystem, where the psychological health education system and partners healthcare system with enough bandwidth, especially 5G technology, could optimize the effect of telemedicine on medical practice and education, is proposed.