bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary Sclerosing Cholangitis due to Drugs With a Special Emphasis on Checkpoint Inhibitors
Authors: Bjornsson Einar S. , Arnedillo Daiana , Bessone Fernando 
Published: December 2024

ABSTRACTBackgroundSecondary sclerosing cholangitis (SSC), is one of the phenotypes of DILI first described in the 1980s. Check point inhibitors (CPIs) are currently the most frequent cause of SCC. Aims: To describe the epidemiology, clinical and biochemical features at presentation, differential diagnoses, pathophysiology, imaging, histological characteristics and management associated with SSC.Materials and MethodsA language and date‐unrestricted Medline literature search was conducted to identify case reports and clinical series on SSC with special emphasis on CPIs (2007‐2023).ResultsWe identified 19 different drugs that have been shown to induce SSC. A total of 64 cases with SSC due to CPIs are presented. This was mostly seen in patients treated with anti‐Programmed cell death (PD)‐1/PD‐L1 inhibitors. The most frequent presenting signs and symptoms were abdominal pain and jaundice. Large‐duct cholangitis induced by CPIs is a very rare condition while small‐duct cholangitis is more common. Nivolumab and pembrolizumab were the most commonly implicated agents. Biopsies have revealed predominant CD8+ T cell infiltration in biliary strictures. Corticosteroids is linked to a low frequency of success and is the only agent recommended to begin the treatment.ConclusionsCPIs‐induced SSC seems to affect the entire biliary system. Clinicians should consider and suspect SSC when a probable CPIs‐induced hepatitis does not respond to corticosteroids. Additionally, further randomized, controlled trials should prospectively investigate alternative therapies for treatment.
Diagnostic ecologies: Medical standards, tinkering, and worker health in Turkey
Authors: Gül Zeynel 
Published: December 2024

AbstractIn Turkey's occupational health system, doctors must use the International Labor Organization's (ILO) standards to classify the chest radiographs of workers at risk of lung diseases caused by dust exposure. Yet these standards do not provide a uniformity of care within the tripartite structure of the occupational health system, which divides disease surveillance, disease diagnosis, and worker compensation into distinct silos. This division often produces ambiguity and unpredictable outcomes for occupational disease claims. The traffic of diagnostic decisions among workplaces and medico‐legal institutions—what I refer to as diagnostic ecologies—shapes medical knowledge. The tripartite organization of the occupational health system in Turkey makes the evaluation of chest radiographs a space where professional expertise and professional ethics are constantly negotiated. A focus on diagnostic ecologies illustrates how disease ontology is distributed across the occupational health system's components.
How Focal Firms Navigate Resource Complementarity Uncertainty of Innovation Ecosystems in Emerging Economies
Authors: Shengxi Yang , Jiaming Yang , Jiang Wei 
Published: December 2024

ABSTRACTThe highly collective uncertainty of the innovation ecosystem is portrayed as unclear resource complementary participants, unstable allocation of participants' relationships, and untimely updating of complementary rules, which led to the complicacy of complementary resource gap identification, the generation of complementary resources, as well as final innovation results. Considering the significant role of innovation ecosystems in emerging economies and the limited understanding of the resource complementary process of innovation ecosystem, we conduct an abductive, exploratory multi‐case analysis to identify the strategies employed by the focal firm within the innovation ecosystem to overcome this collective uncertainty and further reveal the full picture of innovation ecosystem's resource complementarity process. Our study contributes to innovation ecosystem literature by deconstructing ecosystem‐level collective uncertainty in the context of emerging economies. We also fulfill the complementarity research by identifying four resource complementary strategies based on an integrated framework and providing a comprehensive understanding of not only what ecosystem complementarity is but also how it comes from.
Locke and Leibniz on epistemic autonomy
Authors: Marušić Jennifer Smalligan 
Published: December 2024

AbstractThis article argues that Locke's views about the nature of knowledge, on the one hand, and about the proper regulation of probable judgment, on the other hand, give rise to a radical form of individual epistemic autonomy. Three theses are defended: First, Locke's conception of the nature of knowledge implies that the knowledge of other individuals has little (to no) influence on whether one knows something. Locke denies that knowledge is the kind of thing that could, even in theory, be transmitted by testimony. Second, Locke's treatment of probability and probable judgment gives a specific role to testimonial evidence, but within such strict limits that the probable judgments of others should play no role in influencing the strength of one's own judgments. Third, in his New Essays Concerning Human Understanding, Leibniz recognizes the radicalness of Locke's position and sees this as reason to reject aspects of Locke's account of knowledge and his treatment of probable judgment. Finally, these views have implications for how Locke conceives of collective inquiry and the division of epistemic labor among inquirers.
Faith in Frames: Constructing a Digital Game‐Based Learning Framework for Religious Education
Authors: Papakostas Christos 
Published: December 2024

ABSTRACTThis paper discusses the potential of DGBL to facilitate transformation in the context of religious education, arguing for the fact that it is immersive, interactive, and experiential. The paper outlines how this could substantially provide a more engaging learning environment for students, develop critical thinking, and ensure effective learning outcomes. This study explores the advantages and challenges involved in integrating DGBL into curricula for religious education in regard to the alignment between digital game design and pedagogical objectives. These are the important discussions of the application of methodologies in education, constructivist and experiential learning theories, and incorporation of cognitive load optimization strategies to ensure that DGBL does not just enchant students with games but fosters deep understanding of religiously related concepts. Of importance is sharing information to ensure that the content of digital games correctly exemplifies the various traditions of religion and student identity to foster belongingness and respect towards cultural diversity. This paper also takes on board some of the pragmatic issues, among which are professional development by teachers, game design challenges, and possible resistance from other stakeholders who are concerned by the perceived risks associated with gaming. This paper argues that the strategic use of DGBL as a methodology will permit educators to design personalized, engaging, and culturally sensitive learning contexts that enhance students' understanding of and engagement with religious teachings, thus working towards a framework of more inclusive religious education.
VOZ‐dependent priming of salicylic acid‐dependent defense against Rhizopus stolonifer by β‐aminobutyric acid requires the TCP protein TCP2 in peach fruit
Authors: Wang Kaituo , Li Chunhong , Cao Shifeng , Lei Changyi , Ji Nana , Zou Yanyu , Tan Meilin , Wang Jinsong , Zheng Yonghua , Gao Haiyan 
Published: December 2024

SUMMARYVascular plant one‐zinc finger (VOZ) transcription factors (TFs) play crucial roles in plant immunity. Nevertheless, how VOZs modulate defense signaling in response to elicitor‐induced resistance is not fully understood. Here, the defense elicitor β‐aminobutyric acid (BABA) resulted in the visible suppression of Rhizopus rot disease of peach fruit caused by Rhizopus stolonifer. Defense priming by BABA was notably associated with increased levels of salicylic acid (SA) and SA‐dependent gene expression. Data‐independent acquisition proteomic analysis revealed that two VOZ proteins (PpVOZ1 and PpVOZ2) were substantially upregulated in BABA‐induced resistance (BABA‐IR). Furthermore, the interaction of PpVOZ1 and PpVOZ2 and their potential target of the TEOSINTE‐BRANCHED1/CYCLOIDEA/PCF (TCP)‐family protein PpTCP2 screened from protein–protein interaction networks was confirmed by yeast two‐hybrid (Y2H), luciferase complementation imaging and glutathione S‐transferase pull‐down assays. Furthermore, subcellular localization, yeast one‐hybrid, electrophoretic mobility shift assay and dual‐luciferase reporter assays demonstrated that nuclear localization of both PpVOZ1 and PpVOZ2 was critical for their contribution to BABA‐IR, as these proteins potentiated the PpTCP2‐mediated transcriptional activation of isochorismate synthase genes (ICS1/2). The overexpression of both PpVOZ1 and PpVOZ2 could activate the transcription of SA‐dependent genes and provide disease resistance in transgenic Arabidopsis. In contrast, the ppvoz1cas9 and ppvoz2cas9 loss‐of‐function mutations and the voz1cas9 voz2cas9 double mutation attenuated BABA‐IR against R. stolonifer. Therefore, the three identified positive TFs, PpVOZ1, PpVOZ2, and PpTCP2, synergistically contribute to the BABA‐activated priming of systemic acquired resistance in postharvest peach fruit by a VOZ‐TCP‐ICS regulatory module.
Displacement of extracellular chloride by immobile anionic constituents of the brain's extracellular matrix
Authors: Normoyle Kieran P. , Lillis Kyle P. , Egawa Kiyoshi , McNally Melanie A. , Paulchakrabarti Mousumi , Coudhury Biswa P. , Lau Lauren , Shiu Fu Hung , Staley Kevin J. 
Published: December 2024

AbstractGABA is the primary inhibitory neurotransmitter. Membrane currents evoked by GABAA receptor activation have uniquely small driving forces: their reversal potential (EGABA) is very close to the resting membrane potential. As a consequence, GABAA currents can flow in either direction, depending on both the membrane potential and the local intra and extracellular concentrations of the primary permeant ion, chloride (Cl). Local cytoplasmic Cl concentrations vary widely because of displacement of mobile Cl ions by relatively immobile anions. Here, we use new reporters of extracellular chloride (Cl−o) to demonstrate that Cl is displaced in the extracellular space by high and spatially heterogenous concentrations of immobile anions including sulfated glycosaminoglycans (sGAGs). Cl−o varies widely, and the mean Cl−o is only half the canonical concentration (i.e. the Cl concentration in the cerebrospinal fluid). These unexpectedly low and heterogenous Cl−o domains provide a mechanism to link the varied but highly stable distribution of sGAGs and other immobile anions in the brain's extracellular space to neuronal signal processing via the effects on the amplitude and direction of GABAA transmembrane Cl currents.
imageKey points
Extracellular chloride concentrations in the brain were measured using a new chloride‐sensitive organic fluorophore and two‐photon fluorescence lifetime imaging.
In vivo, the extracellular chloride concentration was spatially heterogenous and only half of the cerebrospinal fluid chloride concentration
Stable displacement of extracellular chloride by immobile extracellular anions was responsible for the low extracellular chloride concentration
The changes in extracellular chloride were of sufficient magnitude to alter the conductance and reversal potential of GABAA chloride currents
The stability of the extracellular matrix, the impact of the component immobile anions, including sulfated glycosaminoglycans on extracellular chloride concentrations, and the consequent effect on GABAA signalling suggests a previously unappreciated mechanism for modulating GABAA signalling.
Research on the Emissions and Fuel Efficiency Sensitive Factors of Gasoline Engine Using a Support Vector Machine Coupling Sobol Method
Authors: Li Yinlong , Han Yongqiang , Zhang Kechao 
Published: December 2024

Abstract
With the increasing prominence of energy and environmental issues, research in the field of internal combustion engines is becoming more and more refined. Engines are affected by the coupling of many factors, and it is necessary to decouple and quantify the impact of inputs on the objectives. In this paper, the effect of engine configuration parameters, operating conditions, and fuel parameters on fuel efficiency and emissions was investigated based on a support vector machine coupling Sobol method. The results of Sobol sensitivity analysis show that the most sensitive parameters for both brake specific fuel consumption and carbon monoxide emission are excess air ratio, total hydrocarbon emission and nitrogen oxides emission, engine load, and intake pressure; the first-order indices are 0.72, 0.27, 0.17, and 0.20, respectively. The most sensitive combustion parameters are maximum pressure in the cylinder, indicated mean effective pressure, maximum temperature in the cylinder, and high-temperature range, and the first-order indices are 0.40, 0.25, 0.39, and 0.57, respectively. It can be summarized through all the Sobol indices that, on the one hand, some input parameters, such as excess air ratio, affect fuel efficiency and emissions through the combustion process and, on the other hand, such as oxygen mass fraction directly affects carbon monoxide emission and total hydrocarbon emission by affecting the oxygen concentration in the cylinder. Sensitivity analysis based on the Sobol method coupling support vector machine was proved to be feasible and will provide valuable guidance for the optimization of internal combustion engines.
Effect of Fuel Injection Pressure on Stoichiometric and Lean-Burn Characteristics of Methanol Blended DISI Engine
Authors: Kumar Singh Rahul , Kalwar Ankur , Agarwal Avinash Kumar 
Published: December 2024

Abstract
Alternative fuels and low engine out emissions are the major focus of the engine research community to tackle future fuel demand and meet emission norms. Methanol is a suitable alternative sustainable fuel for spark ignition engines. Methanol has a high-octane number, inherent oxygen in the molecule, and low carbon-containing fuel. In this study, the effect of fuel injection pressure on stoichiometric and lean combustion of M20 (20% v/v methanol + 80% v/v gasoline) was investigated. The results were also compared for M20 and baseline G100 (gasoline). The combustion and performance characteristics of M20 and gasoline changed slightly with fuel injection pressure. However, the effect of fuel injection pressure was significant on emissions. At medium engine speed and load, overall combustion, performance, and emissions characteristics for gasoline were marginally better than M20 for lean and stoichiometric combustion. This study explains the fast combustion of gasoline observed at medium speed and load. Only the advantage of the M20 was seen for NOx emissions. Lean combustion of M20 improved brake-specific fuel consumption, brake thermal efficiency, carbon monoxide, and NOx emissions. The hydrocarbon and smoke opacity were higher for the lean mixture than the stoichiometric mixture for M20. Cyclic variations were within the drivability limit for lean and stoichiometric mixture combustion of M20 and gasoline. A higher fuel injection pressure is suitable for stoichiometric and lean combustion of M20 to achieve high peak pressure, better performance, and lower emissions at medium speed and load.
Exploring Pilot-Assisted Hydrogen High-Pressure Direct-Injection Engines by Numerical Modeling
Authors: Leenders Tom P. E. , Diepstraten Nick , Bekdemir Cemil , van Oijen Jeroen A. 
Published: December 2024

Abstract
Hydrogen (H2) High-Pressure Direct-Injection (HPDI) emerges as a promising combustion concept in heavy-duty engines for GHG emissions reduction through the use of a carbon-free main fuel while preserving the high efficiency of a compression ignition engine. A pilot injection of diesel is employed to act as an ignition source for the main fuel, hydrogen, both of which are directly injected into the combustion chamber. H2 HPDI measurements are conducted under various conditions. To gain insights into the details of the fuel injection and combustion processes, an adequate Computational Fluid Dynamics (CFD) simulation is desired. Modeling such a system requires that the injection properties are accurately prescribed. It is found in the literature, that substantial uncertainties exist in these parameters. This research aims to increase the understanding of H2 HPDI combustion through a numerical investigation. Both measurement and CFD simulation are processed identically, enabling a fair comparison of the apparent rate of heat release (aROHR), which is a key indicator of their combustion phenomena. Reasonable agreement is observed between CFD simulations and measurement data. The uncertainty in the main fuel injection is investigated by varying the inflow boundary conditions. Here it is observed that with the increasing injection pressure and fuel temperature, the jet is ignited earlier and more mixing-controlled combustion is observed. Additionally, a pilot separation sweep is performed, highlighting the importance of the spatial position of the pilot combustion. Retarding the pilot injection significantly suppresses the peak aROHR.
A Fundamental Study on the Potential LSPI Promoting Mechanisms of Ca and Mg Based Oil Detergents
Authors: McAllister Matthew J. , Davy Martin H. , Doherty Luke J. , LePage Laurent M. , Wheeler Christopher 
Published: December 2024

Abstract
Abnormal combustion, in its various forms, has presented a challenge to the design and operation of spark-ignited internal combustion engines for well over a century. During the last decade the relative prevalence of low speed pre-ignition (LSPI) in highly boosted and downsized engines has led to significant research efforts directed at understanding its origins. Two key mechanisms; oil droplet release from the piston top land crevice region and the accumulation and release of in-cylinder deposits, have both been shown to trigger LSPI. With respect to the oil release mechanism, multiple authors have reported a link between LSPI propensity and the calcium treat rate as detergent in the oil additive pack. It is, similarly, widely reported that magnesium based detergent packs do not promote LSPI in the same way. However, no fundamental explanation as to why calcium is ‘bad’ and why magnesium is ‘good’ has yet been presented in the literature. This paper reports the preliminary results from a series of fundamental shock tube experiments exploring the reactions between calcium and magnesium oxides, and a range of gases in relation to their potential as a trigger for LSPI. Visible light emissions are shown from shock heated calcium oxide particles in a 100% carbon dioxide environment at high temperature, T &gt; 1173 K. Unexpectedly, light emitting reactions are also shown for calcium oxide in a 100% nitrogen environment at temperatures T &gt; 773 K, suggesting that there may be a previously unidentified LSPI trigger mechanism in which nitrogen plays a key role. No visible emissions were seen from magnesium oxide powders.
Accelerating Detailed Chemistry Simulations of Hydrogen Combustion in IC Engines Using Reynolds-Averaged Navier-Stokes (RANS) Turbulence Modeling and a Thickened Flame Model
Authors: Sapkota Pradeep , Wijeyakulasuriya Sameera , Liu Shuaishuai , Zhang Yu , Parmar Basu , Gomez-Soriano Josep , Novella Ricardo 
Published: December 2024

Abstract
Green hydrogen, with its potential to significantly reduce transportation CO2 emissions, emerges as a promising solution to combat human-induced climate change. However, challenges such as flame instability and pre-ignition pose significant obstacles to its integration into internal combustion engines (ICEs). Computational fluid dynamics (CFD) is an important tool available for engineers to overcome these challenges towards enhancing engine efficiency, combustion stability and reducing emissions. Hence, novel CFD approaches to simulate hydrogen ICEs in an economical way is of importance. In the current study, hydrogen combustion is simulated in a turbocharged port fuel injection (PFI) spark ignited (SI) engine utilizing detailed chemistry along with a thickened flame model (TFM). The primary objective of employing a TFM is to increase the turbulent flame thickness, thus enabling more economical simulations while maintaining solution accuracy. The turbulence model utilized in this investigation is the RNG k-ϵ model, as this model also facilitates economical simulations. While TFMs are conventionally used with Large Eddy Simulation (LES) turbulence models, the current implementation extends this approach to Reynolds-Averaged Navier-Stokes (RANS) models. RANS models inherently introduce a thickening effect on the flame due to their higher turbulent viscosity. However, additional thickening can be beneficial for hydrogen flames, which tend to be thinner compared to traditional hydrocarbon fuel flames. This model effectively alleviates the computational burden associated with resolving thin hydrogen flames, rendering them computationally efficient for CFD simulations of H2 ICEs. In this study, a mixture-averaged diffusion model combined with detailed chemistry is employed to account for both preferential diffusion and H2 combustion. Several engine operating points are simulated and compared against measured cylinder pressure data, demonstrating good agreement. The utilization of TFM enables the simulation of multiple engine cycles with a significantly reduced wall clock time. The paper compares the cylinder pressure predictions and the run times from RANS simulations with and without the use of TFM with that of LES simulations with TFM to show how the use of TFMs with RANS in hydrogen ICE simulations offer a promising avenue for advancing research in sustainable transportation technologies.
Comparison of Ring Axial Position Measurements and Simulation Results in a Large Bore Engine
Authors: Marzemin Francesco , Higgs Ansel , Rossegger Bernhard , Vareka Martin , Engelmayer Michael , Wimmer Andreas 
Published: December 2024

Abstract
Liner-piston-ring interaction is a crucial driver of blow-by emission and lube-oil consumption in internal combustion engines (ICE). It also largely influences friction losses, as up to 50 percent of the internal friction losses can be attributed to the liner-piston-ring system. A deeper understanding of this tribological system and the complex combustion process in an ICE is necessary for creating cleaner and more robust combustion engines. New ICEs must be capable of facing new industry demands, such as higher peak firing pressures and lower emissions for established and new fuels. Using simulations as an explanatory tool combined with new state-of-the-art measuring systems is fundamental for a better understanding of liner-piston-ring dynamics. Simulation tools, such as the commercial Software AVL EXCITE Piston&Rings, paired with calibration and validation, can be used to simulate the axial ring movement inside the piston grooves during the combustion cycle. The simulation is calibrated using measurements obtained from a large single-cylinder engine equipped with an LEC Smart Telemetry system. It is equipped with displacement sensors capable of measuring the distance between the ring and groove flank during engine operation. This paper compares the simulation’s ring axial position results, before and after calibration from the measurement results, with the sensor outputs and discusses the discrepancies. Ring dynamics are shown to be less stable than simulated values. The ring movement of the second ring and third ring are shown to change between cycles during similar engine operation conditions.