bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Investigation of Secondary Cooling Effect on the Endwall Surface With Vane Trailing Edge Coolant Injection
Authors: Yang Xi , He Wenbin , Lei Jiang , Luo Ding , Chen Wenbin , Hao Xusheng 
Published: August 2024

Abstract
Considering the adequate use of coolant, the secondary cooling effect of trailing edge coolant injection on the downstream endwall surface is investigated in this study. Distributions of adiabatic cooling effectiveness on the endwall surface are obtained through pressure-sensitive paint (PSP) technique in a linear cascade at four mass flowrate ratios (MFR = 1%, 2%, 3%, and 4%) and two density ratios (DR = 1.0 and 1.5). The configurations of trailing edge pressure-side cutback (PC) and central cutback (CC) with three compound angles (β = 15 deg, 30 deg, and 45 deg) are implemented in this study. Reynolds-averaged Navier–Stokes simulations are performed to present the flow field. Results show that the geometry of the cutback slot has a significant effect on the endwall cooling performance. As the compound angle increases, the coolant coverage is expanded in width. A higher density ratio leads to a decrease in the area of coolant coverage, while the distribution is more uniform. Generally, with a higher mass flow ratio, the coolant coverage is greatly improved in area and value, which almost covers the entire downstream endwall surface.
Public health case for microbiome-sparing antibiotics and new opportunities for drug development
Authors: McDonald L. Clifford , Young Vincent B. , Wilcox Mark H. , Halpin Alison Laufer , Chaves Ricardo L. 
Published: August 2024

ABSTRACT

Although antibiotics remain a cornerstone of modern medicine, the issues of widespread antibiotic resistance and collateral damage to the microbiome from antibiotic use are driving a need for drug developers to consider more tailored, patient-directed products to avoid antibiotic-induced perturbations of the structure and function of the indigenous microbiota. This perspective summarizes a cascade of microbiome health effects that is initiated by antibiotic-mediated microbiome disruption at an individual level and ultimately leads to infection and transmission of multidrug-resistant pathogens across patient populations. The scientific evidence behind each of the key steps of this cascade is presented. The interruption of this cascade through the use of highly targeted, microbiome-sparing antibiotics aiming to improve health outcomes is discussed. Further, this perspective reflects on some key clinical trial design and reimbursement considerations to be addressed as part of the drug development path.
Is precarious employment an occupational hazard? Evidence from Ontario, Canada
Authors: Shahidi Faraz Vahid , Liao Qing , Landsman Victoria , Mustard Cameron , Robson Lynda S , Biswas Aviroop , Smith Peter M 
Published: August 2024

ObjectivesTo examine the association between precarious employment and risk of occupational injury or illness in Ontario, Canada.MethodsWe combined accepted lost-time compensation claims from the Workplace Safety and Insurance Board with labour force statistics to estimate injury and illness rates between January 2016 and December 2019. Precarious employment was imputed using a job exposure matrix and operationalised in terms of temporary employment, low wages, irregular hours, involuntary part-time employment and a multidimensional measure of ‘low’, ‘medium’, ‘high’ and ‘very high’ probabilities of exposure to precarious employment. Negative binomial regression models examined exposure to precarious employment in relation to risk of occupational injury or illness.ResultsAfter adjusting for age, sex and year, all indicators of precarious employment were associated with increased risk of injury or illness. Workers with ‘high’ and ‘very’ high’ exposure to precarious employment presented a nearly threefold risk of injury or illness (rate ratio (RR): 2.81, 95% CI 2.73 to 2.89; RR: 2.82, 95% CI 2.74 to 2.90). Further adjustment for physical demands and workplace hazards attenuated associations, though a statistically and substantively significant exposure–outcome relationship persisted for workers with ‘high’ and ‘very high’ exposures to precarious employment (RR: 1.65, 95% CI 1.58 to 1.72; RR: 2.00, 95% CI 1.92 to 2.08).ConclusionsWorkers exposed to precarious employment are more likely to sustain a lost-time injury or illness in Ontario, Canada. Workplace health and safety strategies should consider the role of precarious employment as an occupational hazard and a marker of work injury risk.
Longyearbyen CO2 lab project—from a vision of a CO2-neutral Svalbard to a geoscience data eldorado
Authors: Senger Kim , Betlem Peter , Braathen Alvar , Olaussen Snorre , Sand Gunnar 
Published: August 2024

The Longyearbyen CO2 lab project was initiated in 2006 by the University Centre in Svalbard (UNIS) to establish whether subsurface storage of locally produced CO2 is feasible. Over a decade of drilling operations and geoscientific research concluded that the subsurface was suitable for storing the CO2 generated from the local power plant. The geological ingredients for successful CO2 storage are in place, comprising a ca. 300 m thick, sandstone-dominated reservoir rock capped by an impermeable mudstone-dominated succession. No CO2 was ever injected for storage in Svalbard for economic and political reasons. However, the project generated a wealth of new data, some of which proved critical for studies related to CO2 storage elsewhere. The data were also key to the characterization of fluid flow and geothermal potential in Svalbard, deciphering past climatic changes, unravelling past tectonic events, some of relevance for understanding the plate tectonic evolution of the Arctic, as well as updating the global geological timescale. In this contribution, we briefly outline the history and main achievements of the Longyearbyen CO2 lab project, before describing, categorizing and openly sharing the publicly available data from the project, including peer-reviewed publications (123 so far) and theses (18 PhD and 34 MSc).
Eco-Friendly Synthesis of Novel and Potential Anisylation Adduct and Its DFT Study
Authors: Ravula Shivakumar , Shivunapuram Mahesh , Shaik Khaja Samiuddin , Kothakapu Sridhar Reddy , Laxmi Somarapu Vijaya 
Published: August 2024

This work describes the preparation of [DMAPAS][Formula: see text]Cl− using an eco-friendly approach. Third, fourth, sixth, and seventh green chemical principles were executed in this optimization process. About 99% of yield was obtained by using 1.0 equivalents of 4-methoxybenzenesulfonyl chloride and N, N-dimethylpyridin-4-amine (DMAP) at r.t., in EtOAc (class 3 solvent) under inert atmosphere free and column chromatography free conditions. DFT comparison studies of three regioisomeric anisylation reagents such as [DMAPpAS][Formula: see text]Cl−, [DMAPmAS][Formula: see text]Cl−, and [DMAPoAS][Formula: see text]Cl− were carried out to understand the stability and reactivity of [DMAPpAS][Formula: see text]Cl− adduct. It also gives scope to develop novel protecting groups like O-tosylation and to prepare novel sulfonates and sulphonamides.
An Electrochemical Study Using Experimental Design for the Determination of Prucalopride Succinate via the Optimized Ion Selective Electrode
Authors: Hadad Ghada M. , Abdelsalam Randa A. , Ahmed Bassant S. , Hamdy Abdallah M. 
Published: August 2024

Prucalopride succinate (PCP) was determined by potentiometry using an ion-selective electrode to obtain the most optimum ion-selective electrode. A screening study was carried out to determine the best membrane components, in which a PCP selective electrode was investigated with dioctyl phthalate as a plasticizer in a polymeric polyvinyl chloride polymeric matrix. Sensors were fabricated using phosphotungstic acid as an exchanger and β-cyclodextrin as an ionophore. Then, an optimization process was carried out, which involved the detection of significant factors affecting membrane response variables followed by the establishment of Box Behnken design in which levels of the selected factors, namely, percent of matrix, a ratio of plasticizer: polyvinyl chloride, and Log of soaking concentration were carefully selected (three levels for each factor). The optimized membrane was examined by measuring the slope, LOQ, linearity of PCP, and response time as response variables. Linear responses of PCP within the concentration ranges of 9.99 × 10−8−3.39 × 10−5 mol l−1 were obtained, and a slope of 61.591 ± 1.112 was observed. The selectivity coefficients of the developed sensors indicated excellent selectivity for PCP. The proposed sensor displayed useful analytical characteristics for the sensitive and selective determination of PCP.
Integrative Modeling of Signaling Network Dynamics Identifies Cell Type–Selective Therapeutic Strategies for FGFR4-Driven Cancers
Authors: Shin Sung-Young , Chew Nicole J. , Ghomlaghi Milad , Chüeh Anderly C. , Jeong Yunhui , Nguyen Lan K. , Daly Roger J. 
Published: August 2024

Abstract
Oncogenic FGFR4 signaling represents a potential therapeutic target in various cancer types, including triple-negative breast cancer and hepatocellular carcinoma. However, resistance to FGFR4 single-agent therapy remains a major challenge, emphasizing the need for effective combinatorial treatments. Our study sought to develop a comprehensive computational model of FGFR4 signaling and to provide network-level insights into resistance mechanisms driven by signaling dynamics. An integrated approach, combining computational network modeling with experimental validation, uncovered potent AKT reactivation following FGFR4 targeting in triple-negative breast cancer cells. Analyzing the effects of cotargeting specific network nodes by systematically simulating the model predicted synergy of cotargeting FGFR4 and AKT or specific ErbB kinases, which was subsequently confirmed through experimental validation; however, cotargeting FGFR4 and PI3K was not synergistic. Protein expression data from hundreds of cancer cell lines was incorporated to adapt the model to diverse cellular contexts. This revealed that although AKT rebound was common, it was not a general phenomenon. For example, ERK reactivation occurred in certain cell types, including an FGFR4-driven hepatocellular carcinoma cell line, in which there is a synergistic effect of cotargeting FGFR4 and MEK but not AKT. In summary, this study offers key insights into drug-induced network remodeling and the role of protein expression heterogeneity in targeted therapy responses. These findings underscore the utility of computational network modeling for designing cell type–selective combination therapies and enhancing precision cancer treatment.
Significance: Computational predictive modeling of signaling networks can decipher mechanisms of cancer cell resistance to targeted therapies and enable identification of more effective cancer type–specific combination treatment strategies.
Targeting Catechol-O-Methyltransferase Induces Mitochondrial Dysfunction and Enhances the Efficacy of Radiotherapy in Glioma
Authors: Jiao Meng , Pirozzi Christopher J. , Yu Chen , Bao Xuhui , Hu Mengjie , Pan Dong , Littleton Sejiro , Reynolds Nathan , Saban Daniel R. , Li Fang , Li Chuan-Yuan 
Published: August 2024

Abstract
Radiotherapy (RT) is commonly used to try to eliminate any remaining tumor cells following surgical resection of glioma. However, tumor recurrence is prevalent, highlighting the unmet medical need to develop therapeutic strategies to enhance the efficacy of RT in glioma. Focusing on the radiosensitizing potential of the currently approved drugs known to cross the blood-brain barrier can facilitate rapid clinical translation. Here, we assessed the role of catechol-O-methyltransferase (COMT), a key enzyme to degrade catecholamines and a drug target for Parkinson’s disease, in glioma treatment. Analysis of The Cancer Genome Atlas data showed significantly higher COMT expression levels in both low-grade glioma and glioblastoma compared to normal brain tissues. Inhibition of COMT by genetic knockout or FDA-approved COMT inhibitors significantly sensitized glioma cells to RT in vitro and in vivo. Mechanistically, COMT inhibition in glioma cells led to mitochondria dysfunction and increased mitochondrial RNA release into the cytoplasm, activating the cellular antiviral double-stranded RNA sensing pathway and type I interferon (IFN) response. Elevated type I IFNs stimulated the phagocytic capacity of microglial cells, enhancing RT efficacy. Given the long-established safety record of the COMT inhibitors, these findings provide a solid rationale to evaluate them in combination with RT in patients with glioma.
Significance: Inhibition of catechol-O-methyltransferase, a well-established drug target in Parkinson’s disease, interferes with mitochondrial electron transport and induces mitochondrial double-stranded RNA leakage, activating type I interferon signaling and sensitizing glioma to radiotherapy.
Blood Leukocyte DNA Methylation Markers of Periodontal Disease and Risk of Lung Cancer in a Case–Control Study Nested in the CLUE II Cohort
Authors: Mulvaney Rachel , Pan Yongyi , Zhao Naisi , Teles Flavia , Lu Jiayun , Platz Elizabeth A. , Kelsey Karl T. , Michaud Dominique S. 
Published: August 2024

Abstract

Background:
Periodontal disease and DNA methylation markers have separately been associated with lung cancer risk. Examining methylation levels at genomic regions previously linked to periodontal disease may provide insights on the link between periodontal disease and lung cancer.

Methods:
In a nested case–control study drawn from the CLUE II cohort, we measured DNA methylation levels in 208 lung cancer cases and 208 controls. We examined the association between 37 DNA-methylated 5′—C—phosphate—G—3′ (CpG) sites at three genomic regions, homeobox 4 (HOXA4), zinc finger protein (ZFP57), and a long noncoding RNA gene located in Chr10 (ENSG00000231601), and lung cancer risk.

Results:
Statistically significant associations with lung cancer risk were observed for all 14 CpG sites from HOXA4 (OR ranging 1.41–1.62 for 1 SD increase in the DNA methylation level, especially within 15 years) and 1 CpG site on gene ENSG00000231601 (OR = 1.34 for 1 SD increase in the DNA methylation level). Although CpG sites on gene ZFP57 were not associated with lung cancer risk overall, statistically significant inverse associations were noted for six CpG sites when restricting follow-up to 15 years (OR = 0.73–0.77 for 1 SD increase in the DNA methylation level).

Conclusions:
Key methylation levels associated with periodontal disease are also associated with lung cancer risk. For both HOXA4 and ZFP57, the associations were stronger within 15 years of follow-up, which suggest that, if causal, the impact of methylation is acting late in the natural history of lung cancer.

Impact:
Identifying biological pathways that link periodontal disease and lung cancer could provide new opportunities for lung cancer detection and prevention.
FDA Approval Summary: Asciminib for Ph+ CML in Chronic Phase Treated with Two or More Tyrosine Kinase Inhibitors and for the T315I Mutation
Authors: Pamuk Gulsum E. , Chow Edwin C.Y. , Ionan Alexei C. , Chen Haiyan , Lee Shwu-Luan , Hsu Vicky , Grimstein Manuela , Zheng Nan , Sun Jielin , Charlab Rosane , Gehrke Brenda J. , Vallejo Jonathon , Ehrlich Lori A. , de Claro R. Angelo , Theoret Marc R. 
Published: August 2024

Abstract
On October 29, 2021, FDA granted accelerated approval to asciminib (SCEMBLIX; Novartis), a tyrosine kinase inhibitor (TKI), for the treatment of adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more TKIs, and granted traditional approval to asciminib for adult patients with Ph+ CML in CP with the T315I mutation. The first indication was approved based on major molecular response (MMR) at 24 weeks in the ASCEMBL study, a randomized trial comparing asciminib with bosutinib in patients who had failed two or more TKIs. This indication was ultimately granted traditional approval on October 12, 2022, based on safety data and MMR rate at 96 weeks of 38% [95% confidence interval (CI), 30–46] in the asciminib arm versus 16% (95% CI, 8–26) in the bosutinib arm (P value: 0.001). The second indication was approved based on MMR rate by 96 weeks of 49% (95% CI, 34–64) in the single-arm CABL001X2101 study. The most common (≥20%) adverse reactions included upper respiratory tract infections, musculoskeletal pain, headache, fatigue, nausea, rash, and diarrhea. The most common (≥20%) laboratory abnormalities were thrombocytopenia, neutropenia, anemia, lymphopenia, hypertriglyceridemia, hyperuricemia, and increases in creatine kinase, alanine aminotransferase, aspartate aminotransferase, lipase, and amylase. This manuscript describes the basis for approval of these indications.
Initial learning in the brain: From rules to action
Authors: Fregni Sofia , Wolfensteller Uta , Ruge Hannes 
Published: August 2024

Abstract
We used fMRI to investigate the neural changes and representational dynamics associated with different learning modes during initial learning and subsequent implementation of previously acquired stimulus-response (S-R) associations. We compared instruction-based learning (INS) and trial-and-error learning (TE) via a third observation-based learning (OBS) condition. This was yoked to the TE condition and shared features with both, the INS and TE conditions. During learning, neural changes were observed in the Frontoparietal and Default Mode Networks across learning modes, consistent with a general decrease in cognitive control demand as learning progresses. INS and TE exhibited condition-specific signal changes, which we interpreted in the context of covert motor preparation during INS, and intentional action and increased cognitive control demand during early TE trials, respectively. Multivariate pattern analysis revealed individual rule information in bilateral prefrontal, premotor, and parietal cortices across learning modes. Most regions revealed consistent representations of individual S-R rules between the learning stage and subsequent implementation stage, regardless of the learning mode. This suggests that initially formed S-R rule representations guide task performance during S-R rule implementation, irrespective of how they are acquired. Finally, within the primary motor and sensory cortices, individual S-R rules were decodable during the learning stage not only when motor responses were overtly executed, as in TE, but also in the absence of overt motor execution, as in INS. This finding substantiates previous claims of covert motor preparatory mechanisms during INS.
Primates in the Hood (Primates en el Barrio): Improving knowledge of threatened primates through schools science projects in rural settings in San Martin, Peru
Authors: Ramirez Karla G. , Shanee Sam , Allgas Nestor , Huachaca Karen , Chumbimuni Cindy , Villaseca Andrea 
Published: August 2024

Abstract
We aimed to improve knowledge among high school students on local environmental issues, with emphasis on the ecology and threats to primates in the Alto Mayo Valley of San Martin Region, Peru. The Alto Mayo Valley is home to at least 8 species of primate, including the endemic and Critically Endangered San Martín titi monkey (Plecturocebus oenanthe). San Martin is also the most deforested region of Peru. We used two participatory teaching methods: Experiential learning and inquiry-based education. The learning experiences were activities that guided students to look for solutions to real-life situations. The project consisted of 8 lessons co-designed by us and the participating school teachers, and implemented by the same teachers with our guidance. Lesson 5 was a field trip to a local community conservation area to apply primatological field techniques and gather scientific data. The students’ final product was a video presentation and a poster of their results. One hundred percent of students acknowledged they learned something new about their local environment, primates, conservation, and research. Experiential learning techniques are effective in developing awareness, knowledge and self-advocacy amongst school students. Our inquiry-based method placed students and teachers closer to scientists, helping them to see the role of science in their neighbourhood. This method can be easily adapted to other regions in Peru and globally.
Resonant Experience: An Exploration of the Relational Nature of Meaning and Value
Authors: Barrett Nathaniel F. 
Published: August 2024

Abstract
This paper examines the common notion of “resonant experience”—an experience marked by extraordinarily rich, powerful, or deep meaning—as a manifestation of the relational nature of meaning and value. I propose to define resonance as an enhanced feeling of the relational context in which experience is determined, and I then proceed to show how this concept of resonance can be used to understand the experience of enriched meaning and value in art. This exploration of resonance is inspired by William James’s claim that meaning is based in the direct experience of relation, together with John Dewey’s claim that basic features of experience are intensified in the enjoyment of art. It also draws from the relational framework of ecological psychology, and is intended to contribute to that framework from a philosophical standpoint.
With Swiss Seniors the Climate-Litigation Movement Chalks up Another Hollow Victory
Authors: Zahar Alexander 
Published: August 2024

Abstract
With the European Court of Human Rights’ April 2024 decision, the climate-litigation movement might feel confident that it has demonstrated that a state’s mitigation policy is subject to human rights law. In fact, all that it has managed to do is to convince the Strasbourg court to overextend itself and discredit itself by concocting a position that defies not only law but logic. The human rights framing is too narrow for the problem of climate change. It focuses on the comfort of one particular species, ignoring the rest. Worse, it is irrelevant to the problem, as the reality of it is that each and every member of this species is causing climate change, not their governments, so the issue cannot be presented as one of protecting individuals from the power of government – and therefore not one that engages human rights law.
Diverging Development Paths between China and the West during the Early Modern Period: the Example of the Suction-Lift Pump
Authors: Kink Sabine 
Published: August 2024

Abstract
The need to lift water by means of appropriate equipment is a global phenomenon and has preoccupied all cultures since earliest times. While most basic methods (for example, the bailing with some kind of container by means of a sweep well or a windlass) were shared all over the world, local conditions and crafting skills produced regional developments of more sophisticated devices. This essay examines the impact of the strategically motivated Jesuit transfer of knowledge about the suction-lift pump from the West to China in the early seventeenth century. There, in the face of constant drought disasters, more efficient implements to get hold of well water would seem to have been desperately needed. The nevertheless sluggish adoption of this innovative, though not yet fully mature, hydraulic technology by the responsible Chinese scholar-officials highlights some of the reasons for the emergence of the Great Divergence between China and the West.