bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure 1 from ETx-22, a Novel Nectin-4–Directed Antibody–Drug Conjugate, Demonstrates Safety and Potent Antitumor Activity in Low-Nectin-4–Expressing Tumors
Authors: Lopez Marc , Crompot Emerence , Josselin Emmanuelle , Farina Anne , Rubis Marion , Castellano Remy , Fares Joanna , Wehbe Maria , Collette Yves , Charafe Emmanuelle , Blanchin Stéphanie , Romagne François , Pálfi Anikó , Hechler Torsten , Pahl Andreas , Azim Hatem A. , Lhospice Florence , Mamessier Emilie , Bertucci François , Elands Jack , Préville Xavier , Olive Daniel
Published: November 2024

Epitope characterization of the 15A7.5 antibody. A, The apparent EC50 ratio of chimeric 15A7.5 and 5A12.2 and human HA22 anti–nectin-4 mAbs on normal differentiated human keratinocytes vs. the SUM190 cell line. B, Specificity of chimeric mAb 15A7.5 for human nectin-4. Flow cytometry normalized MFI signal from MDA-MB-231 cells (open triangles) and MDA-MB-231 cells transfected with human nectin-4–expressing plasmid (plain triangles) after incubation with a dose range of chimeric 15A7.5 mAb and staining with a PE goat anti-human antibody. Inlay: MFI signal recovered from MDA-MB-231 cells stained with anti-hNectin-1 (R1.302), anti-hNectin-2 (R2.477), or anti-hNectin-3 (N3.12) mAbs. C, Specificity of humanized mAb 15A7.5 for human nectin-4. The binding profile of humanized 15A7.5 was assessed with a human plasma membrane protein cell array. Shown are confirmation screen images of 293HEK live cells expressing membrane nectin-4 (green) or secreted tethered (blue) that demonstrate the specificity for nectin-4 of humanized mAbs 15A7.5 and 5A12.2. D, Chimeric 15A7.5 mAb binds to the IgV domain of nectin-4. Binding of chimeric 15A7.5 mAb was evaluated by ELISA on wells coated with the complete extra cellular domain of nectin-1 (Nec1-VCC), the complete extra cellular domain of nectin-4 (Nec4-VCC), or the IgV domain of nectin-4 only (Nec4-V). E, Cross-reactivity of chimeric 15A7.5 for cynomolgus nectin-4. Cos cells were transiently transfected with expression plasmids coding for human, cynomolgus, rat, or mouse nectin-4. Cells were incubated with a dose range of chimeric 15A7.5 and stained with PE goat anti-human antibody. F, Epitope of humanized 15A7.5, as determined by deep mutational scanning and represented on the reference structure of human nectin-4. MFI, mean fluorescence intensity.
Global research trends in building-integrated photovoltaics: a bibliometric analysis (1971-2022)
Authors: Tambunan Handrea Bernando , Digwijaya Wigas , Nurfanani Achmad
Published: November 2024

The number of academic publications in the building-integrated photovoltaics (BIPV) field has rapidly grown. Most published articles focus on a specific topic, such as mathematical model, solar architecture design, photovoltaic effect, solar cell, grid-connected, efficiency, performance assessment, economic analysis, optimization, and others with broader focus areas. This work focuses on BIPV research with bibliometric analysis through documents, cited references, authors, affiliations, countries, funding sponsors, sources, words, and conceptual structure based on the Scopus-indexed database between 1971 and 2022. The result shows that BIPV research constantly grows annually with strong collaboration authorship. China is the most relevant country with the top affiliation and funding sponsor to support the BIPV research. The terms conjugated polymers, photovoltaic properties, and organic polymer are identified as niche themes. On the other hand, the terms of conversion efficiency, perovskite, photovoltaic devices, solar cells, efficiency, and photoelectrochemical cell clusters are emerging themes. In the future, BIPV research will move towards microgrids, energy, performance, energy management systems, and energy efficiency issues. The finding will also provide researchers and organizations with a comprehensive understanding of BIPV research areas and new directions for future research.
Web system to enhance technical supervision of incidents at the hydrocarbons regulatory institution in Lima–2023
Authors: Caceres Sanchez Cynthia Elvia , Diburga Evangelista Luis Alfredo , Cano Lengua Miguel Angel , Rosas Culcos Fredy Robert
Published: November 2024

In this article, the implementation of a web system was carried out to improve the process of technical supervision of incidents of a hydrocarbon regulatory company because time was lost in carrying out each process; this research was developed using the SCRUM methodology as it is an agile methodology and adapted to our research. Using the process, events and artifact, it was possible to design the prototypes of the system, architecture, and database. Finally, the implementation was carried out among other important points obtained as results; the average level of optimization of the incident assignment process, derived from the observations, is 91.05% efficiency in assigning incidents to specialists. Regarding the 95% confidence interval for this indicator, it is between 88.98% and 93.11% efficiency, representing two standard deviations with respect to the mean. Regarding the average response time to incidents in all states, obtained from observations, it is 15 days. The 95% confidence interval for this indicator ranges between 14 and 18 days, which represents two standard deviations from the mean. The system is intuitive and not complex. With the implementation of the web system, processes are automated and end user satisfaction is obtained.
Enhanced student attendance and communication in educational management systems
Authors: El Mustapha Louragli , Gmih Yassine , Soussi Sohaib , Abdelmajid Farchi
Published: November 2024

The internet of things (IoT) and radio frequency identification (RFID) technology were explored to devise a beneficial approach for managing student attendance. The research developed a system that uses RFID tags embedded in student bracelets to gather presence data via strategically placed sensors. The system leverages real-time databases and Google technologies to enhance the student experience through an online platform, while also utilizing RFID for authentication. Focusing on improving user experience (UX) through effective design, the proposed system offers a pleasurable and cost-effective solution. Developed using popular web technologies such as Firebase, React.js, and Tailwind, along with Arduino chips and sensors, the system provides a practical solution for managing student attendance, academic performance, and administrative communication. The research highlights the potential of RFID technology in improving student management and academic performance. By decreasing the effort needed by traditional systems and proving cost-effective in the long term, it could act as a potential choice for implementation in educational institutions worldwide.
Impact of usability on continuance usage intention in language learning apps with gamification features
Authors: Ulfiah Ulfiah , Rahthin Rasyadan Muhammad Faris , Utami Wening Tyas , Sunardi Sunardi , Fitria Murad Dina
Published: November 2024

With the increasing popularity of language learning applications, gamification has become one of the approaches frequently integrated to enhance continuance usage intention (CUI). However, how the usability of these gamification features influences the intention to continue usage is not yet fully understood. Through the usability testing and system usability scale (SUS) method, this study evaluates the level of usability of gamification features in language learning applications with a novel research approach that also involves specific analysis regarding usability aspects according to Nielsen, including learnability, efficiency, memorability, errors, and satisfaction towards the CUI, categorized through the SUS statements grouping and then processed using the SPSS application. The study results indicate that the SUS scores show above-average scores for all three applications: Duolingo application at 77.08, Elsa Speak at 70, and Cake Learn at 70.58. Other findings suggest that usability aspects generally significantly influence CUI; however, only the satisfaction variable impacts CUI, which was observed only in Duolingo and Elsa Speak. These findings indicate that the overall usability of gamification features positively impacts CUI using language learning applications, thereby implying the need for continuous development.
Deep learning approaches for analyzing and controlling rumor spread in social networks using graph neural networks
Authors: Manurung Jonson , Sihombing Poltak , Andri Budiman Mohammad , Sawaluddin Sawaluddin
Published: November 2024

The pervasive influence of social networks on information dissemination necessitates robust strategies for understanding and mitigating the spread of rumors within these interconnected ecosystems. This research endeavors to address this imperative through the application of a graph neural network (GNN) model, designed to capture intricate relationships among users and content in social networks. The study integrates user-level attributes, content characteristics, and network structures to develop a comprehensive model capable of predicting the likelihood of rumor propagation. The proposed model is situated within a broader conceptual framework that incorporates sociological theories on information diffusion, user behavior, and network dynamics. The results of this research offer insights into the interpretability of the GNN model’s predictions and lay the groundwork for future investigations. The iterative refinement of the model, consideration of ethical implications, and comparison against traditional machine learning baselines emerge as crucial steps in advancing the understanding and application of deep learning methodologies for rumor control in social networks. By embracing the complexities of real-world scenarios and adhering to ethical standards, this research strives to contribute to the development of proactive tools for rumor management, fostering resilient and trustworthy online information ecosystems.
Exploring Bengali speech for gender classification: machine learning and deep learning approaches
Authors: Dewan Arpita Habiba , Al Ryan Abdullah , Fahad Hossain Md. , Sadekur Rahman Md. , Sajjad Md , Noor Islam Prova Nuzhat
Published: November 2024

Speech enables clear and powerful idea transmission. The human voice, rich in tone and emotion, holds unique beauty and significance in daily life. Vocal pitches vary by gender and are influenced by emotions and languages. While people naturally perceive these nuances, machines often struggle to capture these subtle distinctions. Machines may struggle to detect these nuances, but people effortlessly perceive them. This project aims to use various machine learning (ML) and deep learning (DL) techniques to reliably determine an individual’s gender from a corpus of Bengali conversations. Our dataset comprises 3185 Bengali speeches, with 1100 delivered by males, 1035 by women, and 1050 by those who identify as third gender. We employed six distinct feature extraction techniques to examine the audio data: roll-off, spectral centroid, chroma-stft, spectral bandwidth, zero crossing rate, and Mel-frequency cepstral coefficients (MFCC). Extreme gradient boosting (XGBoost), support vector machines (SVM), K-nearest neighbors (KNN), decision trees classifier (DTC), and random forest (RF) were employed as the five ML algorithms to comprehensively analyze the dataset. For a full study, we also included 1D convolutional neural networks (CNN) from the DL area. The 1D CNN performed extraordinarily well, exceeding the accuracy of all other algorithms with a stunning 99.37%.
Swift and efficient cinnamon plant disease classification using robust feature extraction and machine learning techniques
Authors: Thandapani Sujithra , Selvaraj Durai , Iqbal Mahaboob Mohamed , Chakravarathi Bharathi Venkatakrishnan , Vinayagam Prabhu
Published: November 2024

The extraction of features and textures holds a crucial significance in the realm of image processing and machine vision systems. Even though artificial intelligence (AI) techniques are superior in attaining the best results in image processing, several challenges remain open for further research in computation complexity, memory, and power requirements. In this context, robust preprocessing techniques are required to address such shortcomings and reduce the computational cost of predictive tasks. This paper employed two feature extraction levels to extract the best possible features from images of the cinnamon plant. Local directional positional pattern (LDPP) extracts global image features, while local triangular coded pattern (LTCP) extracts local features. It helps to provide detailed and more relevant information about the image texture. Once features are extracted, identifying and categorizing diverse textures within an image relies on recognizing their unique features. Typically, descriptors serve as the means for representing images in our work. Afterwards, we used ensemble learning to attain better classification results with the help of weak classifiers. Extracted features are provided to machine learning (ML) models like support vector machines (SVM), random forest (RF), and k-nearest neighbors (KNN) for better classification of the cinnamon category.
The use of generative adversarial network as a domain adaptation method for cross-corpus speech emotion recognition
Authors: Farhan Fadhil Muhammad , Zahra Amalia
Published: November 2024

The research of speech emotion recognition (SER) is growing rapidly. However, SER still faces a cross-corpus SER problem which is performance degradation when a single SER model is tested in different domains. This study shows the impact of implementing a generative adversarial network (GAN) model for adapting speech data from different domains and performs emotion classification from the speech features using a 1D convolutional neural network (CNN) model. The results of this study found that the domain adaptation approach using a GAN model could improve the accuracy of emotion classification in speech data from 2 different domain such as the ryerson audio-visual database of emotional speech and song (RAVDESS) speech corpus and the EMO-DB speech corpus ranging from 10.88% to 28.77%, with the highest average performance increase across three different class balancing method reaching 18.433%.
Development a decision support system for selection healthcare chatbot
Authors: Phooriyaphan Sirirak , Rachsiriwatcharabul Natworapol
Published: November 2024

It’s an increasing number of healthcare in many countries. Healthcare chatbot can save money, time and meet patient satisfaction. The healthcare would like to select the best or optimal healthcare chatbot but in the real situations, some healthcare may select the healthcare chatbot by own opinions in the organization with several criteria. The purpose of this research is to design and develop a decision support system (DSS) to select healthcare chatbot under the criteria of: i) functionalities; ii) multilingual ability; iii) usability; and iv) security and privacy. According to this research, it can help healthcare to make a reliable decision. The DSS allows users to select the most suitable alternatives of chatbot. The DSS is analyzed by using analytic hierarchy process (AHP). The result show that the DSS was designed to help in complex decision making and show the making decision of decision maker in the reliable and accurate decision. The result found that it is an appropriate technique for using in the DSS to select the suitable healthcare chatbot in accordance with overall criteria effectively including the sensitivity analysis.
Cascaded H-bridge 7-level inverter application for air exhaust fan drive control of Thu Thiem road tunnel
Authors: Thu Anh An Thi Hoai , Cuong Tran Hung , Khoi Tran Van
Published: November 2024

The Thu Thiem road tunnel in Vietnam is crucial in reducing traffic congestion and ensuring the safety of those passing through, thanks to its ventilation system that generates clean air. This fresh air production is primarily supported by two exhaust fans at both ends of the tunnel in the eastern and western towers. However, the fans have a power capacity of several hundred kW and operate at kilovolt-level voltage, which is unsuitable for conventional inverters. Therefore, this paper proposes a 7-level inverter to feed the exhaust fan drive motor. The 7-level inverter improves the output voltage quality, and the output current and voltage have reduced the harmonic distortion significantly. The outstanding advantages of this inverter are verified through MATLAB/Simulink simulation software compared to a 3-level inverter.
Design and optimization of a linear fiber-reinforced soft actuator for improved linear motion performance
Authors: Md Ghazaly Mariam , Yee Wong Min , Abdullah Zulkeflee , Hasim Norhaslinda , Maisarah Mohd Sobran Nur , Izzuan Jaafar Hazriq , Zainal Nasharuddin
Published: November 2024

The demand for safe and flexible actuators has increased as traditional actuators pose safety risks due to their rigid materials, especially in applications requiring human-machine interaction. This study focuses on designing and optimizing a linear fiber-reinforced soft actuator to enhance linear motion performance while maintaining safety and flexibility. Finite element method (FEM) analysis was used to evaluate the effects of varying key design parameters, including core radius, actuator length, and core wall thickness. The analysis revealed that increasing the core radius leads to greater linear extension, while increasing the actuator’s length and wall thickness reduces extension. Among the tested designs, the R10 design exhibited the highest linear extension, with a 44.41% increase in length compared to the original design. However, the R10 design also showed undesirable bulging at the free end under pressure, which necessitated further optimization. By increasing the thickness of the sheath wall, the bulging was reduced, and the optimized design achieved a 34.53% increase in extension. This study highlights the significance of parameter optimization in fiber-reinforced soft actuators to achieve superior linear motion performance. Future work will explore further improvements in structural stability, sensor integration for precise control, and advanced fabrication techniques for better customization and durability.
Non-centroid-based discrete differential evolution for data clustering
Authors: Poonthong Tanapon , Wetweerapong Jeerayut
Published: November 2024

Data clustering can find similarities and hidden patterns within data. Given a predefined number of groups, most partitional clustering algorithms use representative centers to determine their corresponding clusters. These algorithms, such as K-means and optimization-based algorithms, create and update centroids to give (hyper) spherical shape clusters. This research proposes a non-centroid-based discrete differential evolution (NCDDE) algorithm to solve clustering problems and provide non-spherical shape clusters. The algorithm directs the population of discrete vectors to search for data group labels. It uses a novel discrete mutation strategy analogous to the continuous mutation in classical differential evolution. It also combines a sorting mutation to enhance convergence speed. The algorithm adaptively selects crossover rates in high and low ranges. We use the UCI datasets to compare the NCDDE with other continuous centroid-based algorithms by intra-cluster distance and clustering accuracy. The results show that NCDDE outperforms the compared algorithms overall by intra-cluster distance and achieves the best accuracy for several datasets.
O Gótico Feminino e o Papel da Mulher nos Contos 'Sob as Estrelas' e 'A Neurose da Cor', de Júlia Lopes de Almeida
Authors: Oliveira Tharcylla Beatriz Fontenele
Published: November 2024

The present work comprises the constitution of the feminine gothic in the tales “Sob as estrelas” and “A neurose da cor”, both present in the collection of tales Ânsia eterna (1903), by the brazilian writer Júlia Lopes de Almeida. In this sense, the hypothesis is presented that aspects of this strand are aligned with a female perspective that is expressed by the role of female characters in the narratives. With this, the objective is to investigate the aspects of the feminine gothic in the author's tales, in addition to analyzing the role of the protagonists in relation to this feminine perspective that, sometimes, expresses the anguish of being a woman in society, which results in the presence of an identity narrative.  Thus, the research that followed this article is bibliographical, descriptive and analytical, using for theoretical support the studies proposed by Beauvoir (1949), Woolf (1929), Zolin (2009), Moers (1976) and Williams (1995), which have as a focus the study of aspects of literary fiction written by women.  With the verification of the role played by the protagonists of the short stories in terms of this gender perspective, a recurrent characteristic in women's authorship, it is possible to conclude that Almeida's production impacts the scenario of brazilian female literary historiography, as it verbalizes, in your texts, the challenge and weight of the female experience in the patriarchal context as “the second sex”, becoming a reference in the representation of the desire of countless women for freedom of expression.
Horror e Monstruosidade em Raça Maldita (1900) de Carolina Invernizio: retratos do Gótico Italiano
Authors: Lobão Júlia , Simoni Karine
Published: November 2024

This article aims to analyze the short story Razza maledetta, written by Carolina Invernizio (1851-1916) and published in the collection Nella rete in 1900, highlighting the Gothic and horrific elements of the characters Toni and Mary, namely, the explicit and implicit monstrosity that manifests at different moments in the plot. Simultaneously, there will be a reflection on possible political and sociological meanings of horror in the aforementioned story, and on the author's modus operandi in using characteristic elements of Gothic and horror to describe and incorporate women’s experiences in Italian society at the turn of the 19th to the 20th century. Firstly, a reflection on the absence of women and the Gothic in the Italian literary canon is presented, followed by biobibliographical aspects about the author, and finally, the presentation and analysis of the short story, as indicated.
O eco-horror vegetal em Invasores de Corpos (1955 [2020]), de Jack Finney: simulacro, hiper-realidade e consumo desenfreado
Authors: Garcia Jaimeson Machado , Magossi Priscila Gonçalves
Published: November 2024

Escrito por Jack Finney e publicado originalmente na década de 1950, em meio às tensões da Guerra Fria, Invasores de Corpos ([1955] 2020) aborda o tema da invasão alienígena. A narrativa, ao longo dos anos, tem sido reinterpretada em consonância com as mudanças culturais e sociais, demonstrando sua atemporalidade por permitir diversas leituras. Frente às crescentes preocupações ambientais que dominam os debates contemporâneos, este estudo propõe uma nova análise da obra a partir da perspectiva do eco-horror vegetal (Keetley, 2016). O objetivo é fomentar uma discussão sobre o consumo desenfreado, caracterizado pela liquidação dos sentidos (Baudrillard, 1991), saturação da informação (Morin, 1986) e a mecânica do conformismo (Marcuse, 1979), que culmina na emergência de simulações, simulacros e hiper-realidade (Baudrillard, 1991). A análise conclui que narrativas como Invasores de Corpos ([1955] 2020) podem ser vistas, sob a ótica do horror ecológico vegetal como reflexos da nossa desconexão crítica com a natureza e os desafios dessa relação.
Perfusion‐Based Relative Cerebral Blood Volume Is Associated With Functional Dependence in Large‐Vessel Occlusion Ischemic Stroke
Authors: Lakhani Dhairya A. , Balar Aneri B. , Koneru Manisha , Wen Sijin , Ozkara Burak Berksu , Caplan Justin , Dmytriw Adam A. , Wang Richard , Lu Hanzhang , Hoseinyazdi Meisam , Nabi Mehreen , Mazumdar Ishan , Cho Andrew , Chen Kevin , Sepehri Sadra , Hyson Nathan , Xu Risheng , Urrutia Victor , Luna Licia P. , Hillis Argye , Heit Jeremy J. , Albers Greg W. , Rai Ansaar T. , Faizy Tobias , Wintermark Max , Nael Kambiz , Yedavalli Vivek S.
Published: November 2024

Background

Pretreatment computed tomography perfusion parameter relative cerebral blood volume (rCBV) lesion volume has been shown to predict 90‐day modified Rankin Scale score in small‐core strokes with Alberta Stroke Program Early Computed Tomography Score ≥5, including those with medium‐vessel occlusions (mid and distal M2 segment occlusions). Hence, in this study we aim to assess the performance of different rCBV lesion volume thresholds (rCBV <42%, rCBV <38%, and rCBV <34%) with 90‐day modified Rankin Scale score including patients with large core (Alberta Stroke Program Early Computed Tomography Score <5) and strictly including only patients with anterior circulation large‐vessel occlusion.

Methods and Results

In this retrospective evaluation of our prospectively collected database, inclusion criteria were (1) Computed tomographic angiography confirmed anterior circulation large‐vessel occlusion from September 1, 2017, to October 1, 2023; and (2) diagnostic computed tomography perfusion. Student
t
test, Mann–Whitney
U
test, and χ
2
test were used in the univariate data analysis. Spearman's rank correlation analysis was used to assess correlations. Outcome measure was dichotomized into good functional outcome (90‐day modified Rankin Scale score, 0–2) and poor functional outcome (90‐day modified Rankin Scale score, 3–6) for logistic regression and receiver operating characteristic analysis.
P
≤0.05 was considered significant. In total, 229 patients met our inclusion criteria. The majority of the patients (n=161) in our cohort had M1 occlusion. All the rCBV thresholds were significantly higher in patients with poor 90‐day functional outcomes and were independently associated with the outcome. Spearman's rank correlation analysis revealed a slightly stronger correlation of rCBV <42% (ρ=0.27,
P
<0.001), as compared with rCBV <38% (ρ=0.25,
P
<0.001) and rCBV <34% (ρ=0.24,
P
<0.001) with functional outcome. Receiver operating characteristic analysis revealed that rCBV <42% (area under the curve, 0.67 [95% CI, 0.60–0.74];
P
<0.001) performed marginally better than rCBV <38% (area under the curve, 0.66 [95% CI, 0.59–0.73];
P
<0.001), and rCBV <34% (area under the curve, 0.65 [95% CI, 0.58–0.72];
P
<0.001).

Conclusions

All the rCBV thresholds were independently associated with poor 90‐day functional outcome; however, the rCBV <42% marginally outperformed rCBV <38% and rCBV <34% lesion volumes.
P‐Wave Duration Is Associated With Aging Patterns in Structural Brain Networks
Authors: Haddad Elizabeth , Matloff William , Park Gilsoon , Liu Mengting , Jahanshad Neda , Kim Ho Sung
Published: November 2024

Background

Impaired cardiac function is associated with cognitive impairment and brain imaging features of aging. Cardiac arrhythmias, including atrial fibrillation, are implicated in clinical and subclinical brain injuries. Even in the absence of a clinical diagnosis, subclinical or prodromal substrates of arrhythmias, including an abnormally long or short P‐wave duration (PWD), a measure associated with atrial abnormalities, have been associated with stroke and cognitive decline. However, the extent to which PWD has subclinical influences on overall aging patterns of the brain is not clearly understood.

Methods and Results

Here, using neuroimaging and ECG data from the UK Biobank, we use a novel regional “brain age” method to identify the brain aging networks associated with abnormal PWD. We find associations between short PWD and accelerated brain aging in the sensorimotor, frontoparietal, ventral attention, and dorsal attention networks, even in the absence of overt cardiac diseases.

Conclusions

These findings contribute to our understanding of the relationship between PWD and structural brain aging. This work emphasizes the need for continued study designs that consider brain‐based outcomes related to abnormally short PWD.
Metabolic Syndrome Nonalcoholic Steatohepatitis Male Mouse With Adeno‐Associated Viral Renin as a Novel Model for Heart Failure With Preserved Ejection Fraction
Authors: Shi Yuji , Perez‐Bonilla Patricia , Chen Xian , Tam Kelly , Marshall Mackenzie , Morin Jeffrey , LaViolette Brianna , Kue Nouaying R. , Damilano Federico , Miller Russell A. , Zhang Bei B. , Roth Flach Rachel J. , Hirenallur‐Shanthappa Dinesh
Published: November 2024

Background

Heart failure with preserved ejection fraction (HFpEF) currently accounts for more than half of patients with HF, with limited approved evidence‐based therapies. HFpEF is a complex multifactorial disease associated with hypertension, obesity, diabetes, and renal dysfunction. In addition to our limited understanding of HFpEF pathophysiology, the development of new therapies is partially hindered by the existing translationally relevant preclinical HFpEF models.

Methods and Results

Here, we report the development of a novel 2‐hit HFpEF male mouse model through adding hypertensive stress from the activation of the renin‐angiotensin‐aldosterone system with adeno‐associated viral‐renin (AAV‐renin), to the metabolic syndrome nonalcoholic steatohepatitis (MSNASH, formerly FATZO) mouse (MSNASH+AAV‐renin). To further demonstrate model translatability, MSNASH+AAV‐renin mice were then treated with approved HFpEF therapies sacubitril/valsartan or a combination of sacubitril/valsartan and empagliflozin. We found that the MSNASH+AAV‐renin mouse model demonstrates clinically relevant features of human HFpEF, including preserved ejection fraction, cardiac hypertrophy, left atrial enlargement, diastolic dysfunction, elevated natriuretic peptides, inflammation, and low exercise capacity. We also demonstrate that treatment with approved HFpEF therapies sacubitril/valsartan and the combination of sacubitril/valsartan with empagliflozin improves the cardiac phenotypes of HFpEF in this model.

Conclusions

The MSNASH+AAV‐renin model faithfully represents a severe cardiometabolic HFpEF phenogroup that can be used as a new tool for HFpEF preclinical research and drug discovery.
Phosphodiesterase 9 Inhibition Combined With Valsartan and With Sacubitril/Valsartan in Experimental Ovine Heart Failure
Authors: Scott Nicola J. A. , Charles Christopher J. , Prickett Timothy C. R. , Frampton Christopher M. , Richards A. Mark , Rademaker Miriam T.
Published: November 2024

Background

LCZ696 (sacubitril/valsartan) antagonizes the renin–angiotensin system while simultaneously augmenting the natriuretic peptides (NPs). Inhibition of phosphodiesterase 9 inhibition (PDE9i), which hydrolyses NP‐generated cGMP may be a more specific means of enhancing NP bioactivity. The objective of the present study was to compare for the first time effects of LCZ696 and PDE9i+valsartan in experimental heart failure (HF) and investigate combination PDE9i+LCZ696.

Methods and Results

Seven sheep received, on separate days, intravenous boli of (1) LCZ696, (2) PDE9i+valsartan, (3) PDE9i+LCZ696, and (4) vehicle control, during mild HF and severe HF. Compared with control, LCZ696 and PDE9i+LCZ696 induced similar increases in plasma NPs (greater increments in severe HF), whereas PDE9i+valsartan reduced NP levels. Circulating cGMP was elevated following LCZ696 and PDE9i+valsartan, and further increased with combination PDE9i+LCZ696. All active treatments increased plasma renin and angiotensin II (greater increments in severe HF). Plasma aldosterone was unchanged. Plasma endothelin‐1 was elevated by LCZ696 and PDE9i+LCZ696, but not PDE9i+valsartan. Active treatments reduced arterial and left atrial pressure and peripheral resistance and increased cardiac output (more pronounced in severe‐HF). PDE9i+LCZ696 induced greater hemodynamic changes relative to LCZ696 and PDE9i+valsartan. Treatments had minimal renal effect in mild HF. In severe HF, treatments elevated urine cGMP in association with significant increases in creatinine clearance and diuresis and natriuresis, effects especially prominent with PDE9i+LCZ696.

Conclusions

LCZ696 and PDE9i+valsartan have similar beneficial hemodynamic and renal effects in HF, with combined PDE9i+LCZ696 producing additional improvements. Overall, effects were significantly greater in severe HF. Findings suggest PDE9i might serve as a replacement for neprilysin inhibition or as an adjunct therapy to LCZ696.
Cytokine Adsorption During Ex Vivo Blood Perfusion Improves Contractility of Donation After Circulatory Death Hearts
Authors: Saemann Lars , Pohl Sabine , Wächter Kristin , Georgevici Adrian‐Iustin , Köhler Conny , Jünger Jennifer , Hoorn Fabio , Gharpure Nitin , Großkopf Anne , Korkmaz‐Icöz Sevil , Wenzel Folker , Karck Matthias , Simm Andreas , Szabó Gábor
Published: November 2024

Background

Donation after circulatory death (DCD) hearts have to withstand ischemia/reperfusion injury that is partially driven by proinflammatory cytokines and decreases ventricular contractility. We hypothesize that cytokine adsorption during normothermic ex vivo blood perfusion of DCD hearts reduces the cytokine levels and improves ventricular contractility.

Methods and Results

Porcine DCD hearts were maintained 4 hours by ex vivo blood perfusion with (DCD‐BP
CytoS
, all groups: N=8) or without (DCD‐BP) CytoSorb, followed by 2 hours reperfusion with fresh blood, including left ventricular functional analysis using a balloon catheter. In a control and a DCD group, hearts were evaluated after procurement. We determined lactate and cytokines after ex vivo blood perfusion and the myocardial and left anterior descending artery transcriptome using microarrays after reperfusion. In DCD‐BP
CytoS
, the developed pressure (control: 124±7 mm Hg/s, DCD: 86±4 mm Hg/s, DCD‐BP: 69±11 mm Hg/s, DCD‐BP
CytoS
: 112±9 mm Hg/s;
P
<0.05) and maximal slope of pressure increment (control: 2010±39 mm Hg/s, DCD: 1219±164 mm Hg/s, DCD‐BP: 964±163 mm Hg/s, DCD‐BP
CytoS
: 1794±205 mm Hg/s;
P
<0.05) were higher compared with DCD‐BP and DCD hearts. However, contractility decreased later during reperfusion without CytoSorb. After 4 hours, troponin, lactate (45±5% versus 69±9%,
P
<0.05), IL (interleukin)‐1β, ‐1ra, and ‐8 were lower in DCD‐BP
CytoS
hearts. In the myocardium of DCD‐BP
CytoS
compared with DCD‐BP hearts, inflammatory mediator receptor activity/binding pathways were enriched, and pathways for collagen‐containing extracellular matrix and contractile fiber were underrepresented. In the left anterior descending artery of DCD‐BP
CytoS
hearts, serine/threonine/tyrosine kinase activity and wound‐healing pathways were enriched, and mitochondrial protein‐containing complex and respiratome‐associated pathways were underrepresented.

Conclusions

CytoSorb during ex vivo blood perfusion enhances the maintenance of DCD hearts and is likely to improve graft function after transplantation.
Acute Effects of Cannabis Inhalation on Arterial Stiffness, Vascular Endothelial Function, and Cardiac Function
Authors: Cheung Christian P. , Coates Alexandra M. , Baker Ryleigh E. , Burr Jamie F.
Published: November 2024

Background

The cardiovascular impact of cannabis use is incompletely understood. Although evidence links chronic use to an increased risk of disease and adverse cardiovascular events, few studies have investigated the acute effects of cannabis inhalation on subclinical dysfunction. Furthermore, it remains unknown how method of inhalation and cannabinoid profile modify risk. While controlling for inhalation method and the effects of either Δ‐9‐tetrahydrocannabinol (THC) or cannabidiol (CBD), we examined the acute cardiovascular effects of cannabis use on arterial stiffness, vascular endothelial responsiveness, and cardiac function, as markers of cardiovascular impairment.

Methods and Results

Twenty‐two young, healthy, cannabis users were assessed for arterial stiffness via pulse wave velocity, vascular endothelial function via brachial artery flow mediated dilation, and cardiac function via echocardiography, before and after (1) smoking THC‐predominant cannabis (S‐THC), (2) vaporizing THC‐predominant THC (V‐THC), and (3) vaporizing cannabidiol‐predominant cannabis (V‐CBD). S‐THC and V‐THC increased heart rate (S‐THC: ∆17±15 bpm, V‐THC: ∆16±16 bpm;both
P
<0.0001) and mean arterial pressure (S‐THC: ∆7±6 mm Hg, V‐THC: ∆5±5 mm Hg;both
P
<0.0001) whereas V‐CBD did not (∆1±4 bpm, ∆3±4 mm Hg;both
P
>0.05). After inhalation, pulse wave velocity increased (S‐THC: ∆0.29±0.75 m/s, V‐THC: ∆0.42±0.74 m/s, V‐CBD: ∆0.10±0.44 m/s;
P
=0.002) and diastolic function was reduced ([early/late ratio] S‐THC: ∆‐0.2±0.53, V‐THC: ∆‐0.33±58, V‐CBD: ∆0.01±66;
P
=0.03). Differences in heart rate were related to changes in pulse wave velocity (r
2
=0.2;
P
=0.0002) and diastolic function (r
2
=0.26;
P
<0.0001). Inhalation method did not alter these cannabinoid‐dependent responses.

Conclusions

THC predominant, but not cannabidiol predominant, cannabis elicits increases in heart rate and blood pressure irrespective of inhalation method, which may increase arterial stiffness and reduce diastolic function. These findings implicate THC as a relevant factor for cannabis‐related subclinical cardiovascular dysfunction.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04693884.
The Interaction between Administrative Courts and Investment Tribunals in Egypt
Authors: Elsisi Ahmed A. , Ali Arif H.
Published: November 2024

Investment arbitration has increasingly become one of the primary methods for the settlement of legal disputes between foreign investors and sovereign States. International investment agreements provide foreign investors with direct legal recourse to international arbitration against host States’ adverse actions. However, on the national level, administrative courts may also have jurisdiction to exercise judicial review over the same challenged government actions. The adjudication of the same measures on both levels often leads to an inevitable interaction between investment tribunals and administrative courts. This article examines the interaction between the courts of Majlis al-Dawla in Egypt and international arbitral tribunals and attempts to highlight the points of their collaboration and mutual reliance. The analysis of the interaction shows that the risk of investment tribunals exercising de facto appellate review over domestic courts’ decisions is minimal, not least because both institutions adjudicate disputes under different and distinct legal bases.
The Shaping of Heracles in Creophylus, Pisander, and Panyassis
Authors: Alepidou Apostolia
Published: November 2024

This article explores the shaping of Heracles’s persona in the lost epics of Creophylus, Pisander, and Panyassis. In consultation with relevant literary and artistic accounts, I investigate the hero’s modus operandi within each of these so-called Heracles epics. While scholars have been hindered from envisioning Heracles as a fully fledged character within the framework of these poorly preserved poems, my examination aims to shed light on his dynamic representation in early Greek epic.
al-Yūsī, Tawḥīd and the Theological Structure of Islamic Knowledge
Authors: Gallien Claire
Published: November 2024

Academic studies of Islamic epistemology have predominantly focused on the classical and post-classical periods and neglected works in the “organization of sciences (tartīb al-ʿulūm)” genre from the early-modern period. At that time, the field had already developed several models, including one inspired by Aristotle, the encyclopedic template, and the pedagogical ordering of sciences. These models have been studied by scholars in the history of philosophy and science, history of religion, as well as pedagogy and learning. However, scholars in Divinity faculties have long ignored these works, leading to an inadequate treatment of their theological foundation and function. Bringing theology to the fore, this article offers an appreciation of how theological principles and epistemic holism have framed and shaped the contours of the “organization of sciences” genre from the early-modern period onwards. The article focuses on al-Qānūn fī Aḥkām al-ʿIlm written by Abū ʿAlī al-Ḥasan b. Masʿūd al-Yūsī (d. 1102 AH / 1691 CE) and explains how the interdependent, cohesive, and holistic dimensions of al-Yūsī’s organization of the sciences is directly derived from Islamic theology. More specifically, the article explores the unique structural role of the tri-partite definition of the religion (dīn) as “faith, religion, and spiritual excellence (imān-islām-iḥsān)” in al-Yūsī’s organization of the sciences and the function of tawḥīd in his conception of knowledge.
Toward Dissolving the Institutionalization of “Othering”: Organizational Conditions that Support Shared Responsibility
Authors: Cowhy Jennifer R. , Wong Lok-Sze , Hopkins Megan
Published: November 2024

Federal entitlement policies like Title III and the IDEA help grant multilingual learners (MLs) and students with disabilities (SWDs) access to public schools. Yet they have operated in ways that continue to “other” the very student populations they intend to integrate. Drawing on social network surveys and semi-structured interviews collected from one urban district over 18 months, we ask: To what degree do central office leaders share responsibility for instructional decision-making in literacy and math? And, how did organizational conditions disrupt or perpetuate the “othering” of MLs and SWDs among central office staff? Leveraging a conceptual framework of critical social network analysis and institutional theory, we found that, despite efforts to promote joint-work and shared responsibility across central office departments, regulative, normative, and cultural-cognitive dimensions of the institutional environment continued to “other” special populations leaders from content-area leaders and, thus, the core of instructional decision-making.
Understanding intracity housing market dynamics: A state-space model with Bayesian nonparametric clustering approach
Authors: Wang Yaopei , Tu Yong , Wan Wayne Xinwei
Published: November 2024

Understanding the intracity heterogeneities in housing market dynamics across microgeographic areas is important but challenging due to infrequent transactions. Unlike traditional methods that use trend-based clustering to improve the accuracy of local housing price and rent indices, we propose a novel hybrid model that combines the state-space model and the Bayesian nonparametric clustering approach to cluster neighbourhoods according to their temporal price volatility. We show that our methods improve the performance of traditional methods by 10-40%, using over 889,428 housing transactions in Singapore between 2006 and 2018. We also demonstrate a practical application of our method – monitoring neighbourhoods’ distinct market reactions to macroeconomic or policy shocks, which has important implications for urban planning and housing investment.
Grain Quality of Panicle Portions in Chalky and Low-Chalky Rice Cultivars
Authors: Samonte Stanley Omar PB. , Ponce Kimberly S. , Sanchez Darlene L.
Published: November 2024

Carbohydrate stress reduces grain size and head rice percentage and increases the chalkiness in rice. This study aims to compare low and high-quality cultivars for their milled rice and chalky grain percentages, as well as grain size, in the top, middle, and bottom panicle portions. Low-chalky and chalky long-grain rice cultivars were grown at Beaumont in 2019 and 2022. Panicles were harvested, partitioned into top, middle, and bottom portions, and phenotyped for grain size, head rice percentage, and chalkiness. Grain area reduction percentage from top to middle panicle portions is higher in the low-chalky cultivars, Presidio and Kaybonnet. This could relieve the carbohydrate stress that leads to chalkiness. The rice cultivars were also genotyped for Chalk5 and OsPPDK. The low-chalky cultivars had the same allele as the low-chalk Lemont for Chalk5. Presidio had a different allele for OsPPDK compared with the cultivars tested. Consistent with the genotyping result for Chalk5, Presidio and Kaybonnet had lower chalkiness than LaGrue and Leah. There was a positive correlation between the number of primary panicle branches and head rice percentage. The improvement in breeding efficiency for high grain quality requires phenotypic screening for a high number of primary panicle branches and for low chalky and partially chalky grain percentages.
Effect of kaolin on productivity, anatomical and biochemical responses to water deficit in Pelargonium graveolens grown in sandy soil
Authors: AbuEl-Leil Eman F. , AbdelRahman Mohamed A. E. , Desoukey S. F.
Published: November 2024

The objective of this study was to examine the response of geranium plants to different irrigation levels (100%, 80%, and 60% based on ETo) and Kaolin application rates (0, 100, 200 and 300 ppm) during 2022 and 2023 seasons, at Aly Mobarak Experimental Farm, Horticulture Research Station, located at El-Bustan site, El-Behiera Governorate, Egypt, by using a two-way factorial analysis experimental design. The results revealed that water deficit significantly reduced most studied traits. Irrigation level at 60% based on ETo exhibited poorest performance on growth parameters and decreased fresh yield and essential oil yield by 27.77% 10.73%, respectively as compared with full irrigated plants. However, foliar application of kaolin at 200 and 300 ppm led to increasing biomass accumulation by 28.51, 26.16%, and essential oil yield by 79.51, 89.95%, respectively, as compared with untreated plants grown under the same level of water deficit (60% based on ETo). GC–MS analysis of essential oil showed that water deficit and kaolin application increased geraniol/citronellol ratio and consequently improved oil quality. Results highlight the positive influence of water deficit and kaolin rates on the development and performance of anatomical parameters. Enzymes assay in leaves revealed in an increase superoxide dismutase (SOD) and peroxidase (POD) activities, and decreased in catalase (CAT) activity under water deficit. As for WUE at 60%, followed by 80% based on ETo recorded excellent response for geranium plants which led to more water saving. So, it could be concluded that foliar application of kaolin at 200 and 300 ppm obtained the optimal characteristics of geranium plants under experimental conditions. In particular, essential oil yield and productivity.
Bio-organic fertilizer affects secondary cell wall biosynthesis of Dendrocalamus farinosus by inhibiting the phenylpropanoid metabolic pathway
Authors: Li Shangmeng , Cao Ying , Wang Boya , Fan Wei , Hu Shanglian
Published: November 2024

Bamboo, as a timber plant, holds significant environmental and economic value. Dendrocalamus farinosus is particularly valuable as it serves both as a source of bamboo shoots and timber, offering high yield, strong disease resistance, and superior fiber quality. Our previous study demonstrated that bio-organic fertilizers promoted the growth of D. farinosus and significantly altered the cellulose and lignin content, key components of the secondary cell wall in culms. However, the underlying regulatory mechanisms remain unclear. In this study, we used metabolomic and transcriptomic analyses to uncover the potential mechanisms by which bio-organic fertilizers affect the secondary cell wall biosynthesis in D. farinosus. A total of 1,437 metabolites were identified, with 20 differential metabolites significantly enriched in the phenylpropanoid metabolic pathway in bamboo shoots (7 upregulated; 13 downregulated). We identified 8,075 differentially expressed genes in bamboo shoots, including 72 genes potentially involved in lignin and flavonoid biosynthesis (6 upregulated; 66 downregulated). In internodes, we identified 5,324 differentially expressed genes, including 83 genes potentially involved in secondary cell wall biosynthesis (43 upregulated; 39 downregulated). Quantitative real-time PCR (qRT-PCR) validated the expression patterns of 8 key genes in internodes. The results suggest that bio-organic fertilizers may affect secondary cell wall biosynthesis in internodes by inhibiting the phenylpropanoid metabolic pathway in D. farinosus shoots. Our study offers insights into the efficient utilization of bamboo and lignocellulosic biomass, serving as a valuable resource for future research.