bluuebunny/crossref_metadata_2025_split huggingface dataset:
Realizing the promise of Project Optimus: Challenges and emerging opportunities for dose optimization in oncology drug development
Authors: Gao Wei , Liu Jiang , Shtylla Blerta , Venkatakrishnan Karthik , Yin Donghua , Shah Mirat , Nicholas Timothy , Cao Yanguang 
Published: November 2023

AbstractProject Optimus is a US Food and Drug Administration Oncology Center of Excellence initiative aimed at reforming the dose selection and optimization paradigm in oncology drug development. This project seeks to bring together pharmaceutical companies, international regulatory agencies, academic institutions, patient advocates, and other stakeholders. Although there is much promise in this initiative, there are several challenges that need to be addressed, including multidimensionality of the dose optimization problem in oncology, the heterogeneity of cancer and patients, importance of evaluating long‐term tolerability beyond dose‐limiting toxicities, and the lack of reliable biomarkers for long‐term efficacy. Through the lens of Totality of Evidence and with the mindset of model‐informed drug development, we offer insights into dose optimization by building a quantitative knowledge base integrating diverse sources of data and leveraging quantitative modeling tools to build evidence for drug dosage considering exposure, disease biology, efficacy, toxicity, and patient factors. We believe that rational dose optimization can be achieved in oncology drug development, improving patient outcomes by maximizing therapeutic benefit while minimizing toxicity.
A critical analysis of the binding pocket of Plasmodium falciparum Phosphatidylinositol‐4‐kinase enzyme
Authors: Ncube Nomagugu B. , Govender Krishna K. , Tukulula Matshawandile 
Published: November 2023

AbstractThe Plasmodium falciparum phosphatidylinositol 4‐kinase type III beta (PfPI4KIIIβ), a protease kinase enzyme, has been shown to be vitally important for the survival of the malaria parasite, both in the host and the vector. However, the lack of the three‐dimensional structure and the full structural characterisation of its binding pocket limits its utility and subsequently the development of new, selective, and highly efficacious inhibitors. Thus, the current study is employing a homology modelling and docking strategy in analysing the binding site morphology and key amino acids that are involved in ligand‐substrate complex formation. Our results reveal a homology model whose stability is confirmed by Ramachandran plots and RMSD. Furthermore, docking a few reported PfPI4KIIIβ inhibitors on this model revealed that the binding pocket of PfPI4KIIIβ is hydrophobic and prefers ligands that adopt a twisted conformation. Based on this analysis it can be concluded that these may possibly be the key amino acids whose interaction with the ligands are influenced by the presence of certain functional groups present in a ligand.
Synthesis and Intracellular Localization of 5,6‐Disubsutituted Pyrido[1′,2′;2,3]imidazo[5,1‐a]isoquinolinium Iodides
Authors: Kawakubo Masato , Inoh Yoshikazu , Inaguma Yuko , Kokubugata Rina , Murata Yuki , Matsumura Mio , Furuno Tadahide , Yasuike Shuji 
Published: November 2023

AbstractNovel pyrido[1’,2’;2,3]imidazo[5,1‐a]isoquinolinium iodides independently substituted at their 5‐ and 6‐position were prepared from 5‐iodopyrido[1’,2’;2,3]imidazo[5,1‐a]isoquinolinium iodides using Suzuki‐Miyaura cross‐coupling reaction. The desired coupling products had cationic extended π‐conjugated skeletons and fluoresced strongly in the 420–460 nm region in methanol. In cell staining assay, the 5‐styryl‐substituted compounds, which showed lower fluorescence quantum yields in methanol, emitted high fluorescence in the intracellular environment and were specifically distributed to the endoplasmic reticulum.
Nonclassical Nucleation and Crystallization of LiNbO3 Nanoparticles from the Aqueous Solvothermal Alkoxide Route
Authors: Riporto Florian , Dhouib Ameni , Gheata Adrian , Beauquis Sandrine , Molina Emilie , Guené‐Girard Simon , Galez Christine , Bornet Aurélien , Gautier‐Luneau Isabelle , Gerber‐Lemaire Sandrine , Monnier Virginie , Le Dantec Ronan , Mugnier Yannick 
Published: November 2023

AbstractThe exact molecular reaction pathway and crystallization mechanisms of LiNbO3 nanoparticles under solvothermal conditions are derived through extensive time‐ and temperature‐resolved experiments allowing to track all the transient molecular and solid species. Starting with a simple mixing of Li/Nb ethoxides, water addition is used to promote condensation after ligand exchange with different co‐solvents including alcohols and glycols of variable carbon‐chain length. A nonclassical nucleation scheme is first demonstrated after the identification of new octanuclear complexes with a {Li4Nb4O10} core whose solvophobic interactions mediate their aggregation, thus, resulting in a colloidal gel at room‐temperature. Upon heating, a more or less frustrated aggregation‐mediated crystallization process is then evidenced leading to LiNbO3 nanocrystals of adjustable mean size between 20 and 100 nm. Such a fine control can be attributed to the variable Nb−OR (R = alkoxy/glycoxy ligand) binding interactions at the surface of crystalline intermediates. Demonstration of such a nonclassical nucleation process and crystallization mechanism for LiNbO3 not only sheds light on the entire growth process of multifunctional nanomaterials with non‐perovskite crystalline structures, but also opens new avenues for the identification of novel bimetallic oxoclusters involved in the formation of several mixed oxides from the aqueous alkoxide route.
A fuzzy cognitive map approach to understand agricultural system and food prices in Türkiye: Policy recommendations for national food security
Authors: Ekici Ahmet , Ekici Şule Önsel , Yumurtacı Hüseyinoğlu Işık Özge , Watson Forrest 
Published: November 2023

AbstractOnce one of the few self‐sufficient food countries in the world, Turkey has become dependent on imports to feed its population. Food prices have climbed to among the highest in the world, severely threatening the food security of the country. Most researchers generally attributed the high prices to the increased input costs of agriculture. Although the role of input prices cannot be denied, this paper focuses on a neglected problem that can account for food price inflation: the attitudes and behaviours of farming communities towards agriculture. Through fuzzy cognitive map methodology, known to be very effective in understanding complex networks of problems, we identify and map the relationships among the factors affecting the agriculture system, develop interview and literature‐driven scenarios, and test these scenarios to demonstrate their role in explaining the relationship between attitudes and behaviours of farming communities and food prices in Turkey. Our findings provide recommendations to policymakers.
Understanding the Emotional Labor of English Language Teaching while Black in the United States
Authors: Stevenson Malik 
Published: November 2023

ABSTRACTThere is a robust literature examining emotional labor as it is experienced by English language teachers and how it is prompted by the emotional rules of their employers. However, it has not been sufficiently inclusive of native English‐speaking Black English language teachers (BELTs). Using the method of autoethnography I examine my experiences with emotional labor as I struggle to manage feelings stemming from race‐related stress to present feelings that are aligned with the emotional rules of an intensive English program (IEP) in the United States. Ultimately, this study highlights some of the unique challenges and emotional labor experienced by BELTs, including the endured triggering of race‐related stress in response to workplace racial microaggression and how and why, through the process of emotional labor, outward responses are constructed. I argue that enduring emotional labor brings about implicit oppressive messages for BELTs to either detach from their racial identity to some extent or to leave their field. Additionally, I provide suggestions for how TESOL programs housed in U.S. higher education contexts can address anti‐Black racism.
“My Book Ideas were Spinning in my Head”: Arts‐Rich Bookmaking Experiences to Create and Sustain Multilingual Children's Meaning Making Flows and Authorial Voices
Authors: Choi Julie , Cleeve Gerkens Rafaela , Tomsic Mary 
Published: November 2023

AbstractImportant theoretical developments in TESOL education challenge the monolingual mindset, instead valuing and leveraging students' complex linguistic repertoires alongside their funds of knowledge and identity through translanguaging practices to foster literacy development. Through a case study of an arts‐rich book making experience facilitated by community organization, Kids' Own Publishing, this article uses assemblage thinking to examine how children's semiotic, knowledge, and identity resources interact to support them to create and sustain meaning making flow and to express distinctive authorial voices. Employing a critical content analysis guided by assemblage thinking, we highlight the literacy skills demonstrated in five students' published eight‐page books and show how the interaction of children's meaning‐making resources is best understood through an “assemblage” lens, a process which is under‐researched. Through this lens, we examine the facilitative role of the arts‐rich experience in furnishing vibrant activities, artifacts, and an inspiring physical space that shaped how the children's meaning‐making resources came together as flows. We consider implications for literacy learning, including the need to create conditions for all children's meaning making resources to be drawn upon in text creation in an approach that values what all students, whether they identify as monolingual or multilingual, bring to their learning.
Occurrence, persistence, and ecological risk of bisphenol A in surface water receiving raw leachate from a municipal solid waste open dump in Kerawalapitiya, Sri Lanka
Authors: Matharage Hashinika , Jayaweera Mahesh , Bandara Nilanthi , Jayawardana Daham , Zoysa Kasun 
Published: November 2023

AbstractBisphenol A (BPA) is an anthropogenic chemical compound utilized to manufacture a wide range of consumer products, such as polycarbonate, polyvinyl chloride (PVC), food packages, and thermal papers. Because of its extensive worldwide use, BPA is pervasive in the environment, negatively affecting aquatic life. Therefore, we studied the occurrence, persistence, and ecological risk of BPA in surface water receiving raw leachate from a municipal solid waste (MSW) open dump in Kerawalapitiya, Sri Lanka. Our findings corroborate that the BPA average concentrations in the canal network were 0.4–42.6 µg/L during the wet season and 0.2–4.9 µg/L during the dry season. The levels of BPA at 11 locations (out of 16) during both seasons differed significantly from the upstream sample, where there was no impact from the dump site (p < 0.05), indicating the ubiquitous occurrence and persistence of BPA in the canal network. BPA levels in the waterbodies are greater in the wet period than in the dry period because of the continuous ingress of run‐off‐driven leachate to the canal network. Our study infers that pH and salinity correlate positively with BPA, while temperature, DO, and TSS are negatively correlated with BPA. BPA levels in five locations during the wet season and one during the dry season surpassed the tolerable level of BPA stipulated by the Canadian Federal Environmental Quality Guidelines to safeguard aquatic life, which is 3.5 µg/L. The findings of the acute ecological risk assessment articulate that during the wet season, Mozambique tilapia (Oreochromis mossambicus) and orange chromide (Etroplus maculatus) constitute a high acute risk, while they pose a medium acute risk during the dry season. Our study suggests that the relevant authorities must prevent the ingress of runoff rich with BPA onto the canal network to protect aquatic life.
Re-Storying African (Studies) Pedagogies: Decolonizing Knowledge and Centering Black Agency?
Authors: Andrews Nathan , Khalema Nene Ernest 
Published: November 2023

AbstractThe quest to decolonize this or that has become quite popular these days. In some instances, it is even being applied to general institutional strategies on equity, diversity, and inclusion. But what really is at stake in this endeavor? With specific reference to what we teach and how we engage our pedagogy toward the subject at hand, we ask: What does epistemic decolonization look like? How do we center the voices and perspectives of Black theorists, peoples, and communities in the way we teach and study ‘Africa’? In responding to such questions, this introductory chapter to the volume highlights an argument that accentuates the need to rethink entrenched narratives about Africa and the place of African agency in knowledge production as a way of tackling the enduring legacies of epistemic imperialism. It provides a thematic review of research that has been done on this topic while also suggesting alternative ways of understanding the current context. Overall, the contribution seeks to provide some justification for why the notion of ‘re-storying’ is a useful concept to imagining the possibilities of centering Black agency in our pedagogical choices and our field of study at large, including an account of the hard work that ‘true’ epistemic decolonization will require.
Promoting Entrepreneurship and Innovation: The Institutional Framework
Authors: Braunerhjelm Pontus , Henrekson Magnus 
Published: November 2023

AbstractIn the previous chapters, we have consistently emphasized the importance of entrepreneurship for innovation, renewal, growth, and job creation. However, these beneficial forces do not automatically reflect the individual entrepreneur’s aims. Even if factors such as social recognition and testing one’s ideas influence the desire to become an entrepreneur, the pursuit of profit plays a part that cannot be ignored. When entrepreneurs search for and attempt to create entrepreneurial rents, they are largely governed by the incentives—the reward structure—that prevail in the environment in which they pursue their entrepreneurship. These incentives are essentially determined by the institutional setup of the economic system, which is sometimes called “the rules of the game.” Good institutions or favorable rules are prerequisites for encouraging innovation and entrepreneurship and for channeling entrepreneurial effort towards socially productive venturing.
Modular binary octahedral symmetry for flavor structure of Standard Model
Authors: Ding Gui-Jun , Liu Xiang-Gan , Lu Jun-Nan , Weng Ming-Hua 
Published: November 2023

Abstract
We have investigated the modular binary octahedral group 2O as a flavor symmetry to explain the structure of Standard Model. The vector-valued modular forms in all irreducible representations of this group are constructed. We have classified all possible fermion mass models based on the modular binary octahedral group 2O. A comprehensive numerical analysis is performed, and we present some benchmark quark/lepton mass models in good agreement with the experimental data. Notably we find a minimal modular invariant model for leptons and quarks, which is able to explain simultaneously the masses and mixing parameters of both quarks and leptons in terms of 14 real free parameters including the modulus τ. The fermion mass hierarchies around the vicinity of the modular fixed points are explored.
Psychosocial interventions seem redact kinesiophobia after anterior cruciate ligament reconstruction but higher level of evidence is needed: a systematic review and meta‐analysis
Authors: Naderi Aynollah , Fallah Mohammadi Mohammad , Dehghan Azizallah , Baker Julien S. 
Published: November 2023

AbstractPurposePsychosocial interventions have shown potential in reducing the fear of re‐injury after anterior cruciate ligament reconstruction (ACLR), but this has not been systematically reviewed. The aim of this study was to assess the available evidence on the effect of psychosocial interventions on kinesiophobia after ACLR.MethodsTwo independent researchers conducted a systematic search in the electronic databases including Scopus, PubMed, Web of Science (WOS), SPORTDiscus, PsycINFO, and CINAHL from their inception until May 2022. They included studies that utilised a randomised controlled study design with a control group, and measured kinesiophobia using the Tampa Scale for kinesiophobia in patients who underwent primary ACLR. The outcome of interest was the mean and standard deviation of kinesiophobia. Extracted data were analysed using Comprehensive Meta‐Analysis software, version 3.0 (CMA.V2), employing a random‐effects model to calculate the overall effect estimates of psychosocial interventions on Kinesiophobia. The standardised mean difference with 95% confidence intervals (CIs) was computed based on the mean and standard deviation in each group.ResultsThis systematic review and meta‐analysis included 5 randomised controlled trials with a total of 213 patients who underwent ACLR. The results of the meta‐analysis showed that psychosocial intervention was more effective than non‐psychosocial comparators in reducing kinesiophobia among patients who underwent a primary ACLR (5 trials, MD 0.56, 95% CI 0.28–0.83, p < 0.001). The heterogeneity score was zero (I2 = 0%; n.s. for Cochran’s Q test), indicating no significant variation among the studies.ConclusionsPsychosocial interventions can alleviate kinesiophobia in patients with primary ACLR. Although the limited number of reviewed studies and their methodological limitations precludes drawing a definitive conclusion regarding the effectiveness of psychosocial interventions on kinesiophobia, these promising findings can serve as a basis for developing psychological strategies to manage kinesiophobia in patients with primary ACLR and can also guide future research this issue.Level of evidenceII.Trial registrationThis trial is registered in PROSPERO on December 2021 (CRD42021282413).
Liraglutide ameliorates delirium-like behaviors of aged mice undergoing cardiac surgery by mitigating microglia activation via promoting mitophagy
Authors: Jia Min , Lv Xin , Zhu Tong , Shen Jin-Chun , Liu Wen-xue , Yang Jian-jun 
Published: November 2023

Abstract
Objective
Postoperative delirium (POD) is a prevalent complication in cardiac surgery patients, particularly the elderly, with neuroinflammation posited as a crucial contributing factor. We investigated the prophylactic effects of liraglutide, a GLP-1 analog, on delirium-like behaviors in aged mice undergoing cardiac surgery and explored the underlying mechanisms focusing on neuroinflammation, mitochondrial dysfunction, and synaptic plasticity.

Methods
Using a cardiac ischemia-reperfusion animal model to mimic cardiac surgery, we assessed delirium-like behaviors, microglial activation, NLRP3 inflammasome activation, mitophagy, synaptic engulfment, and synaptic plasticity.

Results
Cardiac surgery triggered delirium-like behaviors, concomitant with heightened microglial and NLRP3 inflammasome activation and impaired mitochondrial function and synaptic plasticity. Pretreatment with liraglutide ameliorated these adverse outcomes. Mechanistically, liraglutide enhanced mitophagy, thereby inhibiting NLRP3 inflammasome activation and subsequent microglial activation. Furthermore, liraglutide counteracted surgery-induced synaptic loss and impairment of synaptic plasticity.

Conclusion
Liraglutide exerts protective effects against delirium-like behaviors in aged mice post-cardiac surgery, potentially through bolstering microglia mitophagy, curtailing neuroinflammation, and preserving synaptic integrity. This highlights the potential of liraglutide as a promising perioperative strategy for delirium prevention in cardiac surgery patients.
Effect of lanthanide and transition metal on the structure, magnetic, and electric properties of nickel ferrites
Authors: Kaiser M. 
Published: November 2023

AbstractA series of nanocrystalline Ni1−xMnxCexFe2−xO4 (x = 0.0, 0.02, 0.04, 0.06, 0.08, and 0.1) were prepared using the citrate auto-combustion method. X-ray diffraction (XRD) indicates that the spinel materials formed in a cubic single phase up to the sample x = 0.02. The average crystallite size is reduced from 61 to 31 nm due to the suppression of grain growth upon cerium occupation at the octahedral site. The cubic spinel structure was confirmed by Fourier-transform infrared (FT-IR) analysis. Scanning electron microscope (SEM) showed agglomerated and rod-shaped structures at various concentrations. AC conductivity and dielectric properties were measured over a frequency range of 20 Hz to 8 MHz. The AC conductivity increases with an enhancement in frequency. The prepared materials have great potential for utilization in microwave devices. The magnetic parameters were estimated from the measured hysteresis loops at room temperature and 100 K using a vibrating sample magnetometer (VSM), which indicated that the samples were suitable for magnetic memory device applications.
Chemical investigation of biological trace evidence; toxicological screening of waste residues obtained from DNA extraction processes
Authors: Di Candia Domenico , Giordano Gaia , Boracchi Michele , Bailo Paolo , Primignani Paola , Piccinini Andrea , Zoja Riccardo 
Published: November 2023

AbstractIn a forensic scenario, if biological stains are found in very small quantities, these are usually collected for DNA analyses, considered essential for the forensic investigation and thus excluding possible investigations by other forensic disciplines as forensic toxicology. We developed an experimental study to evaluate the feasibility of analyzing DNA extraction residues obtained from DNA extraction procedures to perform toxicological analysis, with the aim to extract both genetic and toxicological information without affecting or compromising the genetic sample and/or DNA extraction. DNA extraction from four blood samples (fortified with 5 molecules of interest with a final concentrations of 1 µg/mL, 100 ng/mL, 10 ng/mL and 5 ng/mL, respectively) were analyzed with QIAGEN QIAmp® DNA Mini kit. Three waste residues collected from the DNA extraction were analyzed for the toxicological investigation via Solid-Phase Extraction and High-Performance Liquid Chromatography—Tandem Mass Spectrometry analyses (Thermo Scientific™ TSQ Fortis™ II Triple-Quadrupole Mass Spectrometer). The analytical investigation revealed that our analytes of interest were detected in two different residues of the DNA extraction procedure, allowing both genetic and toxicological analyses without affecting the DNA identification. At last, the experimental protocol was applied to a hypothetical case, with encouraging results and allowing the identification of our molecules of interest.