bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting Poisoning Attacks in Collaborative IDSs of Vehicular Networks Using XAI and Shapley Value
Authors: Bataineh Ahmed Saleh , Zulkernine Mohammad , Abusitta Adel , Halabi Talal
Published: September 2024

Machine learning-based Intrusion Detection Systems (IDSs) for vehicle networks can collaborate to enhance their performance by sharing crucial decisions when individual datasets lack diversity, which hinders effective model training. However, such collaborative coalitions are vulnerable to poisoning attacks, where certain members tamper with training data, leading to wrong predictions by the IDSs. The current solutions to this problem have the following issues: (1) They require accessing the training dataset of IDSs, which raises critical privacy concerns; (2) their heavy reliance on voting mechanisms may exclude clients and fail to detect malicious coalition members when attackers form the majority coalition; and (3) the verification process can potentially expose sensitive information, posing privacy risks. To address these issues and improve the resilience of collaborative IDSs against poisoning attacks, we propose a novel approach that combines XAI (Explainable AI) technology with Shapley value from cooperative game theory. XAI justifies IDS decisions, while the Shapley value identifies poisoning attacks in training datasets by capturing contradictions between explanations and decisions. We tested our implementation using a publicly available dataset and various machine learning models (e.g., RFC, SVM, and LSTM). Our results prove highly promising in detecting poisoning attacks and overcoming the flaws in existing solutions.
EiAP-BC: A Novel Emoji Aware Inter-Attention Pair Model for Contextual Spam Comment Detection Based on Posting Text
Authors: Chrismanto Antonius Rachmat , Winarko Edi , Suyanto Yohanes
Published: September 2024

Detecting spam comments on social media remains a continuously discussed research topic to this day, especially on public figure/celebrity accounts in Indonesia. However, the previous studies only focused on the comments themselves, without considering the context of the posting and the use of emojis in social media. This study proposes a new deep learning model called EiAP-BC (Emoji-aware Inter-Attention Pair BiLSTM CNN) for spam comment detection through a novel approach that considers the contextual information of the posts, enabling the detection of spam comments using the relatedness between the comment and its corresponding post that is usually discarded. This model can also handle emoji content in comments and posts, which is widely used in social media. The model was tested using the SPAMID-PAIR dataset created from social media in the Indonesian language, achieving the highest accuracy of 88% and performing competitively with existing deep learning models. To assess its generalization capabilities, the EiAP-BC model was also evaluated using similar public datasets and models in sentence-pair classification tasks, and an ablation study was conducted to determine the importance of each layer and its coordination. The EiAP-BC model exhibits several advantages in size, training speed, and parameter count compared to existing state-of-the-art models.
Mechanical Characterization of Electrolyzer Membranes and Components Under Compression
Authors: Arthurs Claire , Kusoglu Ahmet
Published: September 2024

Proton-exchange membrane (PEM) water electrolysis is a promising technology for producing clean hydrogen by electrochemically splitting water when paired with renewable energy sources. A major roadblock to improving electrolyzer durability is the mechanical degradation of the cell components, which requires an understanding of their mechanical response under device-relevant conditions. However, there is a lack of studies on the mechanical characterization of the PEM and other components, as well as and their interactions. This study aims to address this gap by using a custom-designed testing apparatus to investigate the mechanics of electrolyzer components in uniaxial compression at 25 and 80 °C. Findings show stress-strain response of components have a varying degree of nonlinearity owing to their distinct deformation mechanisms and morphologies, from porous structures to polymers. These results are used to develop an expression for compressive stress-strain response of Nafion membranes and then analyze the deformation of components under applied pressure by using a 1-D spring network model of cell assembly. This work provides a new understanding of mechanical responses of the electrolyzer membrane and cell components, which can help assess material design and cell assembly strategies for improved electrolyzer durability.
Investigation of SDS on Corrosion Behavior and Discharge Performance of AZ31B Magnesium Alloys in Aqueous Magnesium Air Batteries
Authors: Lu Xiangyu , Zhao Yang , Zheng Zhiteng , Hu Jing , Feng Xingguo
Published: September 2024

To address the issue of high self-corrosion rate of Mg anodes in seawater batteries leading to low discharge efficiency, the green inhibitor, sodium dodecyl sulfate (SDS), was utilized to enhance the discharging performance of AZ31B alloy. The addition of SDS in a 3.5% NaCl solution led to a reduction in the corrosion rate of AZ31B alloy due to the formation of S-containing compounds. During the continuous-discharging period, the addition of 0.05 M SDS increased the anodic utilization efficiency from 64% to 81% and the specific energy density of the entire battery elevated from 1280 to 1912 mAh g−1 (an increase of 49%). The enhancement of the discharge performance of AZ31B Mg alloy in a 3.5% NaCl solution by SDS can be attributed to three aspects: reducing the negative difference effect of the Mg alloy, decreasing the accumulation of corrosion products on the surface of the Mg alloy, and promoting a more uniform dissolution of the Mg alloy.
Optimized n-Butanol Sensing Performance of ZnCeO2 and ZnCuCeO2 Nanocomposites at Room Temperature
Authors: Gopi Krishna Kurugundla , Parne Saidi Reddy , P Nagaraju , Edla Damodar Reddy
Published: September 2024

ZnCeO2 and ZnCuCeO2 nanocomposites (NCs) were successfully synthesized using a simplistic co-precipitation method. The structural, morphological, and optical properties of the nanocomposites were thoroughly characterized using X-ray diffraction (XRD), X-ray photoelectron spectroscopy, Raman spectroscopy, scanning electron microscopy, and ultraviolet-visible spectroscopy. The XRD analysis confirmed the formation of nanocomposites without any secondary phases, revealing average particle sizes of 11.21 nm for ZnCeO2 and 7.02 nm for ZnCuCeO2. The direct band gaps of the nanocomposites were determined to be 3.05 eV for ZnCeO2 and 3.12 eV for ZnCuCeO2, with corresponding refractive indices of 2.19 and 2.14, respectively. Furthermore, the gas-sensing properties of the synthesized nanocomposites were systematically investigated, with a specific focus on their response to n-Butanol gas. Notably, the room-temperature n-Butanol sensing of ZnCuCeO2 NC exhibited enhanced sensing performance, including a rapid response time of 13 s, a quick recovery time of 7 s, and a remarkable sensitivity of 458 for 20 ppm concentration of n-Butanol. These findings underscore the potential of ZnCuCeO2 nanocomposites for practical sensor applications, particularly in the detection of n-Butanol gas, showcasing their promising characteristics for real-world sensing scenarios.
Subthalamic nucleus neurons encode syllable sequence and phonetic characteristics during speech
Authors: Lipski W. J. , Bush A. , Chrabaszcz A. , Crammond D. J. , Fiez J. A. , Turner R. S. , Richardson R. M.
Published: September 2024

Speech is a unique human behavior that requires dynamic execution of precisely timed and coordinated movements, resulting in intelligible vocalizations. Here, we demonstrate that activity of individual neurons in the subthalamic nucleus (STN) of the basal ganglia encode syllable sequence order and phoneme identity during a speech production task. These findings advance our understanding of neural substrates of human speech and shed light on potential involvement of the STN in complex human behaviors.
Phytochemical Characterization and Assessment of Crude Extracts from Justicia adhatoda for Phytotoxic and Cytotoxic Activity
Authors: Nasir Muhammad , Ramash Roha , Fatima Hira , Ashraf Sana , Munir Iqra , Asghar Sundas , Adnan Muhammad , Masood Atifa , Chaudhari Sunbal Khalil
Published: September 2024

Background. The aim of the study was to investigate the cytotoxicity, phytotoxicity, and proximate and phytochemical analysis of methanolic extracts of the leaves of Justicia adhatoda. Methods. Methanolic leaf extract of J. adhatoda was screened for phytotoxic activity by using root length inhibition and seed germination assays. Cytotoxic activity was calculated using brine shrimp lethality bioassay. Plant extracts were also investigated for their proximate composition. The presence of several phytochemicals was tested by employing different methods. Results. Decrease in seed germination and root length, 62.67% and 83.11%, was proportional to the increasing concentration of the methanolic extract of the plant. Cytotoxicity assay results indicated that the methanolic extract possessed significant cytotoxic potential with an LC‐50 of 217 µg/ml. Proximate analysis revealed that the leaves of J. adhatoda contain 9.4% moisture, 90.6% dry matter, 19.25% crude protein, 4.5% crude fat, 8.0% crude fiber, and 11.5% total ash. Conclusion. Methanolic extracts of J. adhatoda leaves showed significant cytotoxic effects and may have potential use in medicine. The J. adhatoda foliar extract shows good inhibitory effects against seed germination and root growth. Therefore, it might be used as soil additive in crops to control weeds. Further research is required to detect and isolate phytotoxins from the plant that might replace synthetic herbicides with eco‐friendly herbicides.
Ethanol Fuel Blending Program in India: Analysis of Environmental, Economic, and Policy Aspects Using System Dynamics Approach
Authors: Kumar Gaurav , Padhy Ramakrushna , Das Debabrata , Narayana Sushmita A.
Published: September 2024

India initiated its ethanol fuel blending program (EBP) two decades ago to enhance energy security, reduce crude imports, and promote low‐carbon transportation. However, despite government initiatives and policies, the EBP has made slower progress than anticipated. For the long‐term adoption and success of the EBP, the following critical areas must be analyzed: integrated ethanol production from multiple feedstocks, demand and linkage to industries requiring ethanol, impact on the environment and revenue prospects, and evaluation of the policy measures adopted. This study addresses these topics by analyzing the interaction between various industries (demand) and ethanol production from multiple sources (supply) using system dynamics modeling. Simulation and scenario analysis have been used to evaluate the environmental and economic performance of ethanol blends under the influence of various policy parameters. The findings indicate that, contrary to the conventional belief, the production of ethanol directly from sugarcane juice does not significantly threaten food security. Higher blending ratios yield enhanced environmental benefits and revenues in the short term, but these are outweighed by the long‐term benefits of lower blending ratios. The findings also indicate that encouraging second‐generation ethanol production from rice stalks and increasing the blending ratios will reduce CO2 emissions. However, the goals set for blending cannot be achieved until measures to diversify feedstocks and improve the infrastructure for ethanol production are scaled up.
In Pursuit of Healthier Learning Environments: High‐Altitude Classroom Ventilation
Authors: Avila Carlos , Tapia Paola , Vallejo Ricardo , Avila Alvaro , Rivera Edgar
Published: September 2024

This study addresses the critical issue of indoor air quality (IAQ) and pathogen transmission within enclosed spaces at high altitudes, focusing on university classrooms in Quito, an Andean city in South America. The aim is to establish safety thresholds for room occupancy and permissible durations of exposure, tailored to this unique environmental context. Through an experimental approach conducted at an elevation of 2900 m above sea level, various natural ventilation strategies were evaluated for their efficacy in mitigating pathogen transmission risks. The study employs the Concentration Decay Test Method to characterize air changes per hour (ACH) and utilizes the Bazant mathematical model to predict occupancy levels based on ventilation, dimensions of the room, respiratory activity, infectiousness rates, and other parameters. Findings highlight the significant impact of ventilation strategies on room occupancy. Notably, higher infectiousness rates and large exposure times drastically reduce permissible occupancy levels, underscoring the importance of effective ventilation in maintaining safety. This research contributes valuable insights for informed decision‐making regarding classroom capacity and safety protocols in Andean higher education settings.
Optimization of the Extraction Process of Effective Components of Eleutherococcus senticosus Using Mathematical Models
Authors: Zhang Shunjie , Wang Yudan , Liu Tianyang , Li Xinzhi , Wang Meiliang , Qiu Youwen
Published: September 2024

Eleutheroside B, eleutheroside E, and isofraxidin are all important active ingredients for medicinal purposes of Eleutherococcus senticosus (Rupr. and Maxim).To improve the efficacy and quality of Chinese medicinal materials, optimizing the extraction process is necessary. By improving and innovating the process, the utilization efficiency of medicinal materials can be enhanced, promoting the effective utilization of Chinese medicinal materials. This experiment focused on three traditional components of Eleutherococcus senticosus, a medicinal plant known for its various bioactive properties. High‐performance liquid chromatography and response surface methodology were employed to investigate the effects of extraction parameters on the yield of these components. Mathematical model analysis was used to optimise the response surface experimental design and to determine the exact extraction conditions for each ingredient. In the extraction method prediction model, the method described in the best group extracted more of the three active ingredients. The extraction rate of the components was increased by 1.33 percent compared to the conventional extraction method. Meanwhile, the R‐square of this prediction model was as high as 0.938. A validated method was used to quantify the three components in 21 samples of Eleutherococcus senticosus from different origins. The results revealed significant variations in the component content among the samples. The recall F1 of cross‐validation sets in the GA‐decision tree of the classifier reaches 0.833. K‐means cluster analysis was performed to classify the samples based on their component profile, providing a basis for quality assessment. The novel content evaluation model developed in this study enabled a reliable and visual comparison of the component differences among the samples and extraction conditions, determining the optimal extraction parameters for each component of Eleutherococcus senticosus. This study offers new techniques and insights for the development and utilization of natural active ingredients from Chinese herbs, with important scientific and practical implications.
Dietary Nanozeolite Powder to Reduce Water Total Ammonia Nitrogen (TAN) and Improve Growth Performance and Plasma Biochemical Indices of Nile Tilapia (Oreochromis niloticus)
Authors: Sarkheil Mehrdad , Ahmadniaye Motlagh Hamidreza , Safari Omid
Published: September 2024

The effects of nanoscale synthetic zeolite powder (NZeP) levels in diet on water quality, growth performance, muscle proximate composition, and some blood biochemical indices of Nile tilapia (Oreochromis niloticus) fingerlings were evaluated in a 60‐day experiment. One hundred eighty fish with an average weight of 5.91 ± 0.45 g were distributed in three different groups of control (basal diet without NZeP), NZP0.5% (basal diet + 0.5% NZeP), and NZeP1% (basal diet + 1% NZeP) with triplicate. The zeolite particles were characterized via field emission scanning electron microscopy coupled with X‐ray energy dispersive spectroscopy (FE‐SEM/EDS), dynamic light scattering (DLS), and X‐ray diffraction (XRD) techniques. The results revealed that the total ammonia nitrogen (TAN) concentration in the NZeP dietary groups decreased compared to the control group after the 20th day of the experiment (p  < 0.05). The TAN concentration in the NZeP1% group was lower than in the NZeP0.5% group on days 50 and 60 (p  < 0.05). The final weight, weight gain, and average daily gain parameters were lower in the fish fed on NZeP1%‐supplemented diet than in other dietary groups (p  < 0.05). The feed conversion ratio value decreased in the NZeP dietary groups compared to the control (p  < 0.05). The lowest FCR value was recorded in the NZeP1% dietary group (p  < 0.05). The muscle crude protein content increased in the fish fed on diet supplemented with NZeP1% in comparison to the control (p  < 0.05). The aspartate aminotransferase (AST) concentration decreased in the plasma of fish fed on NZeP‐supplemented diets compared to the control (p  < 0.05). The plasma glucose concentration was lower in the NZeP1% dietary group than the control (p  < 0.05). In conclusion, the adding nanozeolite powder at a level of 1% to diet had positive effects on water quality, the growth performance, and muscle proximate composition of Nile tilapia fingerlings.
Studying the Humoral Response against SARS‐CoV‐2 in Cuban COVID‐19 Recovered Patients
Authors: Orosa Vázquez Ivette , Díaz Marianniz , Zúñiga Rosales Yaima , Amada Klayris , Chang Janoi , Relova Hernández Ernesto , Tundidor Yaima , Roblejo Balbuena Hilda , Monzón Giselle , Torres Rives Bárbara , Noa Romero Enrique , Carrillo Valdés Danay , Valdivia Álvarez Irinia , Delahanty Fernández Aurora , Díaz Claudia , Solozabal Joaquín , Gil Mileidys , Sánchez Belinda , Rojas Gertrudis , Marcheco Beatriz , Carmenate Tania
Published: September 2024

Understanding the immune response generated by SARS‐CoV‐2 is critical for assessing efficient therapeutic protocols and gaining insights into the durability of protective immunity. The current work was aimed at studying the specific humoral responses against SARS‐CoV‐2 in Cuban COVID‐19 convalescents. We developed suitable tools and methods based on ELISA methodology, for supporting this evaluation. Here, we describe the development of an ELISA for the quantification of anti‐RBD IgG titers in a large number of samples and a similar test in the presence of NH4SCN as chaotropic agent for estimating the RBD specific antibody avidity. Additionally, a simple and rapid ELISA based on antibody‐mediated blockage of the binding RBD‐ACE2 was implemented for detecting, as a surrogate of conventional test, the levels of anti‐RBD inhibitory antibodies in convalescent sera. In a cohort of 273 unvaccinated convalescents, we identified higher anti‐RBD IgG titer (1 : 1,330, p  < 0.0001) and higher levels of inhibitory antibodies blocking RBD‐ACE2 binding (1 : 216, p  < 0.05) among those who had recovered from severe illness. Our results suggest that disease severity, and not demographic features such as age, sex, and skin color, is the main determinant of the magnitude and neutralizing ability of the anti‐RBD antibody response. An additional paired longitudinal assessment in 14 symptomatic convalescents revealed a decline in the antiviral antibody response and the persistence of neutralizing antibodies for at least 4 months after the onset of symptoms. Overall, SARS‐CoV‐2 infection elicits different levels of antibody response according to disease severity that declines over time and can be monitored using our homemade serological assays.
Enhanced Stochastic Approaches of 1 : 4 PCCV in Nuclear Power Plant: Uncertainty Quantification and Fragility Assessment
Authors: Ju Bu-Seog , Son Ho-Young
Published: September 2024

Probabilistic evaluation of the internal pressure capacity before excessive leakage is essential for ensuring preemptive response in case of a severe accident in a prestressed concrete containment vessel (PCCV) subjected to internal pressure in a nuclear power plant. Therefore, in this study, we conducted a fragility analysis to evaluate the probabilistic internal pressure capacity for damage states before excessive leakage. Three damage states were classified, and a finite element (FE) model was developed based on the experimental test results of a 1 : 4 scale PCCV under the overpressurization condition at Sandia National Laboratory. The three damage states were determined as the onset of inelastic behavior (DS1), onset of leakage (DS2), and excessive leakage (DS3). Fragility analysis was performed using a validated FE model to consider uncertainties in material properties and prestressing force. The Latin hypercube sampling method was used to perform uncertainty quantification, and normality tests verified that the samples exhibited normal distributions. The internal pressure capacity variability in DS1 and DS2 was higher than that in DS3. DS1 is the point at which the compressive deformation caused by the prestressing force was converted into tensile deformation because of the increase in the internal pressure, which resulted in tensile concrete cracking. Furthermore, DS2 is the state in which localized damage of the liner occurred and cracks in the concrete spread. Thus, the internal pressure capacity for DS1 and DS2 exhibited high variability because of the uncertainty of the prestressing force and material properties. Moreover, the median capabilities of DS1, DS2, and DS3 were ~1.85, 2.61, and 3.45 times the design pressure, respectively. Therefore, material and structural uncertainties in nuclear power plants should be appropriately considered, and a conservative assessment of the damage state before excessive leakage should be performed for preemptive response in the case of severe accidents.
Moxibustion Regulates the BRG1/Nrf2/HO‐1 Pathway by Inhibiting MicroRNA‐222‐3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis‐Associated Colorectal Cancer
Authors: Wang Xuejun , Ji Haiyang , Yang Yanting , Zhang Dan , Kong Xiehe , Li Xiaoying , Li Hongna , Lu Yunqiong , Yang Guang , Liu Jie , Wu Huangan , Hong Jue , Ma Xiaopeng
Published: September 2024

Oxidative stress is crucial in ulcerative colitis (UC) and colitis‐associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA‐222‐3p (miR‐222‐3p) can protect against oxidative stress in IECs, which ameliorates colonic injuries in UC mice and prevents the conversion of UC to CAC. In this case, we hope to explore whether moxibustion can alleviate UC and CAC by inhibiting miR‐222‐3p based on mouse models of UC and CAC. After herb‐partitioned moxibustion (HPM) intervention, the disease activity index (DAI) and colon macroscopic damage index (CMDI) were significantly reduced in UC mice, and the number and volume of intestinal tumors were decreased considerably in CAC mice. Meanwhile, we found that HPM suppressed miR‐222‐3p expression and upregulated the mRNA and protein expression of Brahma‐related gene 1 (BRG1), nuclear factor erythroid 2‐related factor 2 (Nrf2), heme oxygenase‐1 (HO‐1), while inhibiting Kelch‐like ECH‐associated protein 1 (Keap1) expression in IECs of UC and CAC mice. With changes in reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH‐Px), and inflammatory cytokines interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α), we verified that HPM protects against oxidative stress and inflammation in IECs of UC and CAC mice. The effect of HPM was inhibited in miR‐222‐3p overexpression mice, further demonstrating that the protective effect of HPM on UC and CAC mice was through inhibiting miR‐222‐3p. In summary, HPM regulates the BRG1/Nrf2/HO‐1 pathway by inhibiting miR‐222‐3p to attenuate oxidative stress in IECs in UC and CAC.
Energy‐Saving Optimization Design of Propeller Boss Cap Fin Based on BP Neural Network Coupled with Northern Goshawk Optimization Algorithm
Authors: Li Chunjin , Cao Yang , Xu Hongrui , Jiang Tao , Liu Chengyu
Published: September 2024

Facing the escalating global energy demand and environmental pressures, efforts to enhance ship efficiency and reduce carbon emissions have become pivotal strategies in addressing energy challenges. This study focuses on optimizing propeller boss cap fin (PBCF), proposing a strategy that integrates a backpropagation neural network (BPNN) with an intelligent optimization algorithm. PBCF’s positions relative to the propeller are expressed parametrically, and the sample space for PBCF parameters is constructed using Latin hypercube sampling. Building upon this, a BPNN model is established, with design parameters as inputs and hydrodynamic performance calculated by computational fluid dynamics as outputs. Simultaneously, the approximate model trained by the neural network serves as the objective function for the northern goshawk optimization algorithm, significantly enhancing the iteration speed. After determining the PBCF’s position parameters, the optimal performance airfoil is chosen as the PBCF profile from seven airfoil types. Finally, visualization techniques were employed to compare the flow field distributions of the optimized fin and the original propeller. The results demonstrate that the optimized fins effectively absorb tangential kinetic energy from blade flow, reduce hub cap pressure differences, and suppress post‐hub vortices. Under specified design conditions, the optimized fins enhance the propulsion system’s efficiency by 1.5%. This study underscores the transformative potential of intelligent optimization techniques in shaping the future of maritime engineering, providing sustainable solutions to global energy challenges.
Empowering of Oncology Patients and Informal Caregivers: Analysis of an Interdisciplinary Seminar Model for Breast Cancer and Gyneco-Oncological Patients
Authors: Hollaender Hannah , Ortner Petra , Koenig Alexander , Erickson Nicole , Hermelink Kerstin , Degenhardt Tom , Di Gioia Dorit , Mahner Sven , Harbeck Nadia , Wuerstlein Rachel
Published: September 2024

Introduction: The interdisciplinary empowerment seminar aims to familiarize patients and informal caregivers (ICs) with supportive measures, focusing on understanding disease, therapy, and side effect management. Methods: The seminar, conducted in two courses over 1-month intervals prior to chemotherapy, included lectures, supportive materials, Q and A sessions, and individual discussions with experts in nutrition, exercise, psycho-oncology, and complementary medicine. Evaluation is based on a self-developed questionnaire and questionnaires on QoL (EORTC-QLQ-C30, BR23, CX24, OV28), anxiety and depression (HADS-D) at week 0, 5, 9, and 12. A control group with standard of care was evaluated at baseline and after 12 weeks. Results: Between October 2020 and May 2021, 19 patients and 9 ICs participated in the seminar. The control group included 20 patients. 96.4% of participants were highly satisfied with the seminar and would recommend it. QoL deterioration was more pronounced in the control group (control: week 0 = 67.6; week 12 = 61.7; intervention: week 0 = 60.8; week 12 = 60.7). This trend could not be proven by analysis of interaction (mixed ANOVA: p = 0.114). Increased confidence of participants’ knowledge about side effects was shown, and ICs reported higher confidence in knowledge and coping with the disease. Conclusions: The seminar received positive feedback and indicated increased knowledge and a trend toward better QoL preservation. Larger studies are needed for confirmation. The seminar effectively addressed unique needs, bolstering confidence and knowledge. Interdisciplinary patient and caregiver empowerment seminars can improve disease-related knowledge and positively affect QoL at the start of chemotherapy. Informational needs can be satisfied. Offering educational seminars and fostering individualized support networks can increase quality of care.
Paroxysmal Nocturnal Hemoglobinuria, Pathophysiology, Diagnostics, and Treatment
Authors: Panse Jens Peter , Höchsmann Britta , Schubert Jörg
Published: September 2024

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis (IVH) due to diminished or absent inhibition of the complement system because of deficient expression of cell-anchored complement regulating surface proteins. IVH leads to heterogeneous symptoms such as anemia, abdominal pain, dyspnea, fatigue and increased rates of thrombophilia. Inhibitors of the terminal Complement cascade can reverse IVH leading to a significant reduction of disease burden such as thrombembolic events and also mortality. Summary: Therapeutic inhibitors of the terminal complement cascade such as eculizumab or ravulizumab significantly improve overall survival through IVH-inhibition. However, not all patients experience complete disease control with normalization of hemoglobin levels and absolute reticulocyte counts (ARC) under terminal complement inhibition as a significant part of patients develop extravascular hemolysis (EVH). EVH can be clinically relevant causing persistent anemia and fatigue. New proximal complement inhibitors (CI) mainly targeting complement component C3 or factors of the amplification pathway such as pegcetacoplan, danicopan, and iptacopan became available and are meanwhile approved for marketing. Additional complement-inhibiting strategies are under clinical development. A switch from terminal to proximal CI in patients with significant EVH can achieve hemoglobin and ARC normalization and significant improvement in quality of life (QoL). Additional approvals of proximal CI agents for the treatment of hemolytic PNH in the first line are available for pegcetacoplan and iptacopan. So far, no evidence-based algorithm is available for decision-making in first-line treatment of which type of drug should be used for individual patients. Key Messages: Terminal CIs in hemolytic PNH patients can block IVH and have led to a dramatically improved survival. Proximal CIs ameliorate anemia and improve QoL in patients with relevant EVH. However, more (real-world) data are needed to demonstrate long-term improvement in all patients with hemolytic PNH, especially those under first-line treatment with proximal CI.
A Retrospective Analysis of the Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors at The Ottawa Hospital Cancer Center over the Last Decade Including COVID-19 Pandemic Period
Authors: Alrehaili Mohammad , Phillips William J. , Asmis Tim , Vickers Michael , Marginean Horia , Goodwin Rachel
Published: September 2024

Introduction: The incidence of neuroendocrine tumors (NETs) is rising. Our objective was to assess trends in gastroenteropancreatic (GEP)-NETs diagnosis (June 2010 to June 2021) at TOHCC and to explore whether early COVID-19 pandemic data impacted these trends. Methods: This was a single-center retrospective chart review of data collected from June 2010 to June 2021. We searched all databases, including OACIS/EPIC, PACS, and OPIS and found 647 GEP-NET patients. Descriptive analyses were performed using frequencies and related percentages. Results: Of 647 patients with GEP-NETs, the small bowel was the most common primary location (n = 210, 32.4%), followed by the pancreas (n = 118, 18.2%), and unknown primary location (n = 99, 15.3%). Most of the cases were classified as metastatic or locally advanced at the initial presentation. There has been no significant variation in the frequency distribution of these cases over the last decade. Stages 1 and 2 were found in 158 cases (23.8%), and lower gastrointestinal (GI) tumors were the most common disease among them (n = 88, 55.7%). There were 5 lower GI cases in 2010–2011 and average number per registration year was 5.5 until 2016–2017, after which time the number of cases increased to 10, 15, 11, and 13 during the last 4 years. Regarding early-stage pancreatic and upper GI NETs, the total number of cases was 52 (32.9%) and 18 (11.4%), respectively. The average number of cases per registration year for pancreatic tumors was 4.7, while that for upper GI tumors was 1.6 over the last decade. Discussion: At our center, most GEP-NETs presented in an advanced setting. Small bowel is the most common location overall. The incidence of early-stage disease has increased. Disease detection for all GEP-NETs was consistent throughout the last decade, except for the lower GI cases that have increased since mid-2017, perhaps reflecting the adoption of Ontario FIT testing. Despite endoscopy closures and disruption of some diagnostic services during the pandemic, cases of GEP-NETs for all stages did not decrease.
Efficacy and Safety of Etrasimod in Patients with Ulcerative Colitis in Japan: Data from the Phase 3 ELEVATE UC 12 and ELEVATE UC 40 JAPAN Trials
Authors: Takeuchi Ken , Hisamatsu Tadakazu , Nakase Hiroshi , Matsuoka Katsuyoshi , Keating Michael , Yuasa Hirotoshi , Oe Motoki , Arai Shoko , Mazur Rafal , Hibi Toshifumi
Published: September 2024

Introduction: Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Here, we report the primary analysis of a phase 3 trial evaluating the efficacy and safety of etrasimod in patients from Japan with moderately to severely active UC. Methods: Patients from Japan who completed the 12-week ELEVATE UC 12 induction trial could enroll in the 40-week ELEVATE UC 40 JAPAN maintenance trial for a combined 52-week treatment period. Patients in this Japan cohort continued their baseline assigned treatment (etrasimod 2 mg QD or placebo) from ELEVATE UC 12. Efficacy was assessed at week 12 and week 52. Treatment-emergent adverse events (TEAEs) pooled from both trials were assessed up to 52 weeks of exposure. Results: The Japan cohort comprised 32 and 16 patients who received etrasimod and placebo, respectively. A numerically greater proportion of patients who received etrasimod versus placebo achieved clinical remission at week 12 (etrasimod: 14.3%; placebo: 7.1%) and week 52 (etrasimod: 25.0%; placebo: 7.1%); a similar trend was observed for all key secondary efficacy endpoints. TEAEs occurred in 84.4% (27/32) and 62.5% (10/16) of patients who received etrasimod and placebo, respectively. No new safety signals were detected. Conclusion: In these induction and maintenance trials evaluating etrasimod in patients from Japan with UC, numerically higher proportions of patients who received etrasimod versus placebo achieved efficacy endpoints. Efficacy and safety findings were consistent with those from the global ELEVATE UC trial populations.
Impact of Pre-Stroke Frailty on Outcome Three Years after Acute Stroke: The Nor-COAST Study
Authors: Munthe-Kaas Ragnhild , Lydersen Stian , Quinn Terry , Aam Stina , Pendlebury Sarah T. , Ihle-Hansen Hege
Published: September 2024

Introduction: We aimed to explore the predictive value of pre-stroke frailty index (FI) on functional dependency and mortality 3 years after stroke. Methods: Based on the Rockwood 36-item FI score, we calculated the pre-stroke FI from medical conditions recorded at baseline in the multicenter prospective Nor-COAST study 2015–2017. Participants with a FI score and a modified Rankin scale (mRS) 0–6 3 years post-stroke were included in this study. We used logistic regression analysis with unfavorable mRS (over 2 vs. 0–2) at 3 years, or dead within 3 years, as dependent variable, and frailty and pre-stroke mRS, one at a time, and simultaneously, as predictors. The analyses were carried out unadjusted and adjusted for the following variables one at a time: Age, sex, years of education, stroke severity at admission, infections treated with antibiotics and stroke progression. We report odds ratio (OR) per 0.10 increase in FI. Results: At baseline, the 609 included patients had mean age 72.8 (standard deviation [SD] 11.8), 261 (43%) were females, and had a FI mean score of 0.16 (SD 0.12), range 0–0.69. During 3 years, 138 (23%) had died. Both the FI, and pre-stroke mRS, were strong predictors for unfavorable mRS (OR 4.1 and 2.7) and dead within 3 years (OR 2.2 and 1.7). Only adjusting for age affected the result. The OR for pre-stroke mRS decreased relatively more than the OR for FI when entered as predictors simultaneously. Conclusions: FI is a stronger predictor than premorbid mRS for prognostication after stroke.
Impact of Lipidic Plaque on In-Stent and Stent Edge–Related Events After PCI in Myocardial Infarction: A PROSPECT II Substudy
Authors: Kjøller-Hansen Lars , Maehara Akiko , Kelbæk Henning , Matsumura Mitsuaki , Maeng Michael , Engstrøm Thomas , Fröbert Ole , Persson Jonas , Wiseth Rune , Larsen Alf Inge , Jensen Lisette Okkels , Nordrehaug Jan Erik , Omerovic Elmir , Held Claes , James Stefan , Mintz Gary S. , Ali Ziad A. , Stone Gregg W. , Erlinge David
Published: September 2024

BACKGROUND:

Lipid content in untreated nonobstructive coronary artery lesions is associated with adverse clinical outcomes, and residual in-stent or stent edge lipid may worsen outcomes after percutaneous coronary intervention (PCI).

METHODS:

Near-infrared spectroscopy-intravascular ultrasound was performed before and after PCI in patients with myocardial infarction. We evaluated the impact of lipid assessed by near-infrared spectroscopy (maximal lipid core burden index over 4 mm [maxLCBI
4mm
]) along with intravascular ultrasound information including residual plaque burden on in-stent or edge-related major adverse cardiac events (MACE) in de novo PCI-treated culprit coronary artery lesions. The primary end point was culprit lesion-related MACE (CL-MACE), defined as cardiac death, myocardial infarction, or unstable or progressive angina either requiring revascularization or with rapid lesion progression and classified as in-stent or stent edge–related.

RESULTS:

During a median follow-up of 3.8 years, 25 CL-MACE (11 stent edge–related, 13 in-stent, and 1 in-lesion without a stent) occurred in 1041 PCI-treated lesions in 768 patients. Pre-PCI or post-PCI measures of lipid content were not related to in-stent CL-MACE. However, stent edge–related CL-MACE was increased if both the post-PCI stent edge maxLCBI
4mm
was greater than the upper quartile (108.7) and the stent edge plaque burden was >50% (adjusted odds ratio, 4.11 [95% CI, 1.12–15.2];
P
=0.03).

CONCLUSIONS:

In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), CL stent implantation leaving behind greater stent edge–related lipid and uncovered plaque burden was associated with an increased risk of stent edge–related CL-MACE during follow-up. In contrast, CL lipid content was not related to in-stent CL-MACE.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02171065.
Prognostic Value of Murray Law-Based QFR (μQFR)-Guided Virtual PCI in Patients With Physiological Ischemia
Authors: Chen Lianglong , Yan Yuanming , Zhong Jiaxin , Chen Ping , Chen Wei , Xu Chaoxiang , Chen Long , Tu Shengxian , Luo Yukun
Published: September 2024

BACKGROUND:

Quantitative flow ratio (QFR)-based virtual percutaneous coronary intervention (PCI) is associated with improved post-PCI physiological results. Murray law-based QFR (μQFR) is a new method for physiological assessment that has higher feasibility and efficiency. The purpose of this study was to investigate the performance of μQFR-guided virtual PCI in improving post-PCI outcomes.

METHODS:

The QUITE RIGHT study (Quantitative Flow Ratio Virtual Stenting and Angiography Guided Percutaneous Coronary Intervention) is a prospective, multicenter, blinded, randomized, controlled superiority study. Eligible patients were randomized 1:1 to either the μQFR-guided virtual PCI group or the angiography-guided PCI group. The primary end point was the proportion of the target vessels with a post-PCI μQFR ≥0.90, accepted as an optimal post-PCI physiological outcome.

RESULTS:

A total of 622 patients with 666 vessels were enrolled. The optimal physiological outcome was reached more often in the μQFR-guided virtual PCI group (absolute difference, 9.1% [95% CI, 4.53–13.76];
P
<0.001). The μQFR-guided virtual PCI group had a better QFR value, a lower contrast agent dose and x-ray dose, and a more appropriate stent length than the angiography-guided group.

CONCLUSIONS:

The QUITE RIGHT study showed that the μQFR-guided virtual PCI strategy is superior to angiography-guided PCI in terms of physiological outcomes. The μQFR-guided virtual PCI strategy is associated with lower contrast and x-ray doses and a more appropriate stent length.

REGISTRATION:

URL:
https://www.chictr.org.cn/
; Unique identifier: ChiCTR2100045452.
Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial
Authors: Jia Ping , Ji Qiang , Zou Zhouping , Zeng Qi , Ren Ting , Chen Weize , Yan Zhixin , Shen Daoqi , Li Yang , Peng Fangyuan , Su Ying , Xu Jiarui , Shen Bo , Luo Zhe , Wang Chunsheng , Ding Xiaoqiang
Published: September 2024

BACKGROUND:

Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery.

METHODS:

This prospective, single-center, double-blind, randomized controlled trial involved 509 patients at high risk for AKI who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. Patients were randomized to receive RIPC (4 cycles of 5-minute inflation and 5-minute deflation on 1 upper arm with a blood pressure cuff) 24 hours before surgery or a sham condition (control group) that was induced by 4 cycles of 5-minute inflation to a pressure of 20 mm Hg followed by 5-minute cuff deflation. The primary end point was the incidence of AKI within the prior 7 days after cardiac surgery. The secondary end points included renal replacement therapy during hospitalization, change in urinary biomarkers of AKI and markers of myocardial injury, duration of intensive care unit stay and mechanical ventilation, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90.

RESULTS:

A total of 509 patients (mean age, 65.2±8.2 years; 348 men [68.4%]) were randomly assigned to the RIPC group (n=254) or control group (n=255). AKI was significantly reduced in the RIPC group compared with the control group (69/254 [27.2%] versus 90/255 [35.3%]; odds ratio, 0.68 [95% CI, 0.47–1.00];
P
=0.048). There were no significant between-group differences in the secondary end points of perioperative myocardial injury (assessed by the concentrations of cardiac troponin T, creatine kinase myocardial isoenzyme, and NT-proBNP [N-terminal pro-brain natriuretic peptide]), duration of stay in the intensive care unit and hospital, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90.

CONCLUSIONS:

Among high-risk patients undergoing cardiac surgery, delayed RIPC significantly reduced the occurrence of AKI.

REGISTRATION:

URL:
https://www.chictr.org.cn
; Unique identifier: ChiCTR2000035568.
Kinetics and Prognosis Value of CCL5/RANTES at the Acute Phase of ST‐Segment–Elevation Myocardial Infarction
Authors: Brun Camille , Moulin Florentin , Leboube Simon , Hayek Ahmad , Kaczmarczyk Andrea , Saleh Iyad Abou , Prieur Cyril , Varillon Yvonne , Bonnefoy‐Cudraz Eric , Mewton Nathan O. , Bidaux Gabriel , Crola Da Silva Claire , Paillard Melanie , Ducreux Sylvie , Bochaton Thomas
Published: September 2024

Background

RANTES (regulated upon activation, normal T cell expressed, and secreted) or CCL5 (CC chemokine ligand 5) is a chemokine that mediates chemotaxis and activation of T cells, monocytes, mast cells, and dendritic cells. It is involved in the pathogenesis of several diseases, including atherosclerosis, but its role at the acute phase of myocardial infarction (MI) is unclear. Our objective is to determine whether the serum level of RANTES is a marker of the severity of acute MI.

Methods and Results

The study included 250 consecutive patients with ST‐segment–elevation MI who underwent percutaneous coronary intervention in a prospective cohort. Peripheral venous blood samples were taken at 5 time points and ELISA was performed. Major adverse cardiovascular events were prospectively recorded over the 12‐month follow‐up. Serum RANTES level raised from 12.9 (8.0–20.7) ng/mL at H0 to 13.9 (7.4–22.4) ng/mL at H4 and decreased gradually until 1 month at 9.7 (5.4–13.6) ng/mL (
P
<0.0001). RANTES area under the curve (AUC) level was not correlated with infarct size (
r
=−0.03,
P
=0.70) or left ventricular ejection fraction assessed by magnetic resonance imaging (
r
=0.02,
P
=0.80). Patients with a RANTES AUC serum level below the first tertile value of the population (411.0 ng.h.mL
−1
) were more likely to have a major adverse cardiovascular event during the first 12 months after ST‐segment–elevation MI (hazard ratio [HR], 2.9 [1.3–6.6],
P
=0.01). In a multivariable Cox regression analysis, serum level below the first tertile remained associated with an increased risk of experiencing major adverse cardiovascular event during the follow‐up (adjusted HR, 2.6 [1.2–5.8],
P
=0.02).

Conclusions

A low level of circulating RANTES post ST‐segment–elevation MI was associated with an increased risk of experiencing major adverse cardiovascular event and might be a valuable prognostic marker in patients with ST‐segment–elevation MI.
Prediction of Severe Baseline Asymptomatic Carotid Stenosis and Subsequent Risk of Stroke and Cardiovascular Disease
Authors: Poorthuis Michiel H.F. , Hageman Steven H.J. , Fiolet Aernoud T.L. , Kappelle L. Jaap , Bots Michiel L. , Steg Ph. Gabriel , Visseren Frank L.J. , Bhatt Deepak L. , de Borst Gert J.
Published: September 2024

BACKGROUND:

Risk models to identify patients at high risk of asymptomatic carotid artery stenosis (ACAS) can help in selecting patients for screening, but long-term outcomes in these patients are unknown. We assessed the diagnostic and prognostic value of the previously published Prevalence of ACAS (PACAS) risk model to detect ACAS at baseline and to predict subsequent risk of stroke and cardiovascular disease (CVD) during follow-up.

METHODS:

We validated the discrimination and calibration of the PACAS risk model to detect severe (≥70% narrowing) ACAS with patients from the Reduction of Atherothrombosis for Continued Health registry. We subsequently calculated the incidence rates of stroke and CVD (fatal and nonfatal stroke or myocardial infarction or vascular death) during follow-up in 4 risk groups (low, medium, high, and very high, corresponding to sum scores of ≤9, 10–13, 14–17, and ≥18, respectively).

RESULTS:

Among 26 384 patients, aged between 45 and 80 years, without prior carotid procedures, 1662 (6.3%) had severe baseline ACAS. During ≈70 000 patient-years of follow-up, 1124 strokes and 2484 CVD events occurred. Discrimination of the PACAS model was 0.67 (95% CI, 0.65–0.68), and calibration showed adequate concordance between predicted and observed risks of severe baseline ACAS after recalibration. Significantly higher incidence rates of stroke (
P
trend
<0.011) and CVD (
P
trend
<0.0001) during follow-up were found with increasing PACAS risk groups. Among patients with high PACAS sum score of ≥14 (corresponding to 27.7% of all patients), severe baseline ACAS prevalence was 11.4%. In addition, 56.6% of incident strokes and 64.9% of incident CVD events occurred in this group.

CONCLUSIONS:

The PACAS risk model can reliably identify patients at high risk of severe baseline ACAS. Incidence rates of stroke and CVD during follow-up were significantly higher in patients with high PACAS sum scores. Selective screening of patients with high PACAS sum scores may help to prevent future stroke or CVD.