bluuebunny/crossref_metadata_2025 huggingface dataset:
Relativistic spin-0 Duffin–Kemmer–Petiau equation in Bonnor–Melvin–Lambda solution
Authors: Ahmed Faizuddin , Bouzenada Abdelmalek
Published: March 2024

In this paper, we conduct a comprehensive exploration of the relativistic quantum dynamics of spin-0 scalar particles, as described by the Duffin–Kemmer–Petiau (DKP) equation, within the framework of a magnetic space-time. Our focus is on the Bonnor–Melvin–Lambda (BML) solution, a four-dimensional magnetic universe characterized by a magnetic field that varies with axial distance. To initiate this investigation, we derive the radial equation using a suitable wave function ansatz and subsequently employ special functions to solve it. Furthermore, we extend our analysis to include Duffin–Kemmer–Petiau oscillator fields within the same BML space-time background. We derive the corresponding radial equation and solve it using special functions. Significantly, our results show that the geometry’s topology and the cosmological constant (both are related to the magnetic field strength) influence the eigenvalue solution of spin-0 DKP fields and DKP-oscillator fields, leading to substantial modifications in the overall outcomes.
A Novel Automatic Map Matching Method Based on Hybrid Computing Framework of Hidden Markov Model and Conditional Random Field
Authors: Hu Dongfeng , Zong Liansong
Published: March 2024

In recent years, automatic map matching has received great technical progress. However, when it comes to vague matching situations such as improper vocabulary use, there still lack reliable solutions. To handle the current gap, this paper proposes a novel automatic map matching method based on the hybrid computing framework of hidden Markov model (HMM) and conditional random field. First, the data filtering is completed by performing second-order transformation towards automatic matching conditions of HMM. Then, the data classification is completed using automatic data classification based on the conditional random field. After that, a hybrid computing framework with spatial elements and layer selection is built to generate map matching results. Finally, some simulation experiments are conducted for evaluation. For one thing, the trend of matching accuracy changes under specified conditions is basically the same as that of nonspecified conditions. The maximum difference in matching calculation values is about 3 times. However, once the vocabulary continues to increase, the difference in matching results between the two narrows to 10–20%. For the other thing, the matching accuracy of a specified state is higher than that of sending a specified state. While nonspecified fuzzy matching accuracy is about 3 times higher and nonspecified precision matching accuracy is about 50% higher.
Intelligent Financial Risk Warning for Enterprises Through Knowledge Graph-Based Deep Learning
Authors: Zheng Jie , Wu Xiaoyao , Tan Lan , Xu Peng , Xu Haiyu , Guo Zhiwei , Li Chun
Published: March 2024

The financial risk warning methods for enterprises have always been a practical concern. In digital society, the computational intelligence has brought more spirit to this demand. This paper first introduces the current situation of the development of Knowledge graph technology, describes the deep learning fusion method based on Knowledge graph, and expresses the feasibility of this study. Then, according to the requirements of Knowledge graph, it completes the method fusion of core data training and extraction, and completes the adaptive deep learning design for the Beautiful SCOP database, and establishes a STDE-FG financial risk early warning model. Through empirical analysis, the shortcomings of this model were identified, and a comparison of optimized and optimized results was completed. Two aspects of phenomenon can be found from experimental results. For one thing, the accuracy of the unoptimized STDE-FG early warning model has been improved by 37.5–55.3% compared to traditional prediction models, but the prediction value during legal person changes has a greater error than traditional prediction values. For another, the optimized STDE-FG early warning model has also improved its accuracy in predicting new investments and equity changes, with improvements of 17–32% and 16–28%, respectively, with significant changes. This model will have a positive impact on improving enterprise risk management capabilities and reducing financial risk costs.
Development of a Fully Differential-Difference Transconductance-Based Filter for Cardiac Troponin Sensor
Authors: Shailaja J. , Ravindran R. S. Ernest
Published: March 2024

Acute myocardial infarction (AMI) is one of the foremost global health threats. Human cardiac troponin I (cTnI) is an effective and golden biomarker for accurately diagnosing AMI. Owing to higher fatality worldwide, an accurate, rapid diagnosis of AMI is highly significant at the early stage for effective treatment. This study designed a novel portable cardiac troponin sensor using a fully differential-difference transconductance-based fifth-order double-notch low pass filter (FDdiff_5thDNLPF) for accurate and early diagnosis of AMI by identifying cTnI. The developed biosensor system can identify cTnI from the blood samples. The twofold ion-sensitive gated field effect transistor (TISG-FET), which can provide a dynamic range, high sensitivity, and high selectivity to target analyte, is used to identify cTnI level and transform the cTnI concentration to drain the current signal. The differential-input instrumentation amplifier (DiffInp_IA) is used as a preamplifier to receive and amplify the input current. The FDdiff_5thDNLPF circuit removes unwanted noises and eliminates available frequencies greater than 50 Hz powerline interference. The signals are then provided to an intermediate amplifier and converted to digital form using an analog-to-digital converter (ADC) circuit. Further, the digital signals have been processed through a central processing unit (CPU), and the data can be displayed. The proposed system for cTnI detection is simulated on the cadence Virtuoso tool. As a result, the proposed system exhibited a minimum detection limit of 0.31 pg/ml, a wide linear range among 1–1000 pg/ml and higher sensitivity of 131 pA pg[Formula: see text] ml[Formula: see text].
IMPULSIVE DIFFERENTIAL EQUATION MODEL IN HIV-1 INHIBITION: ADVANCES IN DUAL INHIBITORS OF HIV-1 RT AND IN FOR THE PREVENTION OF HIV-1 REPLICATION
Authors: MONDAL SRIJITA , PETERS JAMES F. , GHOSH PRIYANKA , SARKAR ASHIS KUMAR , SASMAL SOURAV KUMAR
Published: March 2024

Reverse transcriptase (RT) and integrase (IN) are two pivotal enzymes in HIV-1 replication. RT converts the single-stranded viral RNA genome into double-stranded DNA and IN catalyzes the integration of viral double-stranded DNA into host DNA. Currently, dual inhibitors of HIV-1 RT and IN have become a hotspot in new anti-HIV drug research and development. A dual inhibitor of HIV-1 RT/IN does the same thing as the two independent drugs would do. In this paper, we develop a mathematical model comprising a system of nonlinear differential equations describing HIV-1 RT/IN catalyzed biochemical reactions based on Michaelis–Menten enzyme kinetic reaction. In the formulated model we incorporate HIV-1 RT/IN dual inhibitor which simultaneously works as a non-nucleoside RT inhibitor and IN inhibitor. To examine the efficacy of HIV-1 RT/IN dual inhibitor in the treatment of HIV-1 infection, we have introduced a one-dimensional impulsive differential equation model and determined an effective dosing regimen for applying the inhibitor numerically. Furthermore, the exact closed form solution of the impulsive differential equation model is carried out by using the Lambert W function and the local stability of the periodic solution is also obtained analytically. The results obtained from analytical as well as numerical studies provide a basic idea to investigate the minimum dose with the highest efficacy for administering HIV-1 RT/IN dual inhibitors to prevent HIV-1 infection.
DYNAMICS AND BLOW-UP CONTROL OF A LESLIE–GOWER PREDATOR–PREY MODEL WITH GROUP DEFENCE IN PREY
Authors: PATRA RAJESH RANJAN , MAITRA SARIT , KUNDU SOUMEN
Published: March 2024

In this paper, we designed a population model that shows how a prey species defends itself against a generalist predator by exhibiting group defence. A non-monotonic functional response is used to represent the group defence functionality. We have demonstrated the model’s local stability in the vicinity of the coexisting equilibrium solution employing a local Lyapunov function. Condition for existence of Hopf bifurcation is obtained along with its normal form. The suggested model has been validated by numerical simulations, which have also been used to verify the acquired analytical results. The parameters are subjected to sensitivity analysis by utilizing partial rank correlation coefficient (PRCC) and Latin hypercube sampling (LHS). The Z-type dynamic method is used to prevent population blow-up.
On Construction of Subgame Perfect Nash Equilibria in Stackelberg Games
Authors: Caruso Francesco , Carmela Ceparano Maria , Morgan Jacqueline
Published: March 2024

Identifying a Subgame Perfect Nash Equilibrium (SPNE) of a two-player Stackelberg game could be not a manageable task, especially when the players have a continuum of actions and the follower’s best reply correspondence is not single-valued. Aim of the paper is to investigate the issue of construction of SPNEs in Stackelberg games by exploiting perturbations of both the action sets and the payoff functions of the leader and the follower. To achieve the goal, since the limit of SPNEs of perturbed games is not necessarily an SPNE of the original game even for classical perturbations, we prove under nonrestrictive convergence conditions how to produce an SPNE starting from a sequence of SPNEs of general perturbed games. This result allows to describe a procedure to find SPNEs that can accommodate various types of perturbations. More precisely, under mild assumptions on the data of the original game, we show that a large class of perturbed games (including, for example, perturbation approaches relying on the Tikhonov and entropic regularizations or motivated by altruistic and antagonistic behaviors) satisfies the convergence conditions for constructing an SPNE. The specific SPNE selections associated to such a class, together with their possible behavioral interpretations, are discussed and an illustrative example is provided.
Simultaneous Identification of Vehicle Load and Structural Damage on Renyihe Bridge
Authors: Ji Guo-Mu , Liu Xiao-Chen , Yuan Yuan , Guo Ya-Xin , Chen Jin-Qiao , Hu Hao-Ran , Yang Wei-Jie , Liu Guang-Dong , Fan Xiao , Cheng Xiao-Xiang , Hou Shi-Tong
Published: March 2024

Simultaneous identification of vehicle load and structural damage is an issue of practical significance in structural health monitoring and maintenance of in-service concrete bridges. However, most methods proposed in history to deal with this engineering issue are solely based on data from a single source of structural vibration response measurement, which are subjected to problems such as incomplete understanding of the structural health, the computational inefficiency and the easy failure of the monitoring system. To this end, this paper proposes a new method of synthesizing data generated from two different types of sensors (the strain gauges and the accelerometers) to simultaneously identify the vehicle load and the structural damage which is established on the theories of weigh-in-motion method based on the strain influence line. The new method, which is supposed to be able to well solve the problems with the traditional approaches disseminated to the profession, is formulated in a flowchart for use, and applied to the actual Renyihe Bridge (a concrete rigid-frame continuous highway bridge with spans of [Formula: see text]) to validate its effectiveness. The results suggest that the new method is of high accuracy in use in low vehicle speed scenarios and superior to the traditional simultaneous identification approach based on unitary structural acceleration sensing.
An Enhanced Mapping Interpolation ISPH–FVM Coupling Method for Simulating Two-Phase Flows with Complex Interfaces
Authors: Xu Yixiang , Yang Gang , Hu Dean
Published: March 2024

In this paper, an enhanced mapping interpolation ISPH–FVM coupling method is developed to improve the accuracy and stability of two-phase flows simulation. Similar to the original ISPH–FVM coupling method, the coupling framework between the numerical schemes of ISPH and FVM is established at the overlapping region of the ISPH particles and the FVM grids. Although the original ISPH–FVM coupling method can effectively predict movement and deformation of the two-phase interface, it is difficult to ensure the mass conservation in the flow domain during the information transfer between ISPH particles and FVM grids, thus weakening the numerical accuracy of interaction between different fluid phases. To improve the mapping interpolation accuracy and ensure the mass conservation, a volume fraction correction scheme combined with the particle approximate interpolation technique is introduced to form an enhanced mapping interpolation ISPH–FVM coupling method. The effect of surface tension is assessed by the continuum surface force (CSF) model. Several 2D/3D numerical cases are given to verify the efficiency and robustness of the present ISPH–FVM coupling method. Numerical results demonstrate that the enhanced mapping interpolation developed in the ISPH–FVM coupling method can reproduce the two-phase flow with complex interfaces effectively.
Remarks on the global monopole topological effects on spherical symmetric potentials
Authors: Bakke K.
Published: March 2024

In this paper, we study the topological effects of the global monopole spacetime on the energy eigenvalues of spherical symmetric potentials in the nonrelativistic regime. We deal with the radial equation by using the Wentzel, Kramers and Brillouim (WKB) approximation. In the cases where the energy levels of the [Formula: see text]-waves can be achieved, the WKB approximation is used based on the Langer transformation.
On the performance of carbon fiber structural batteries with temperature
Authors: Du Chunzhi , Zhu Shaoqian
Published: March 2024

Carbon fiber structural batteries, which combine structural and functional properties, have good energy storage capacity while bearing loads have received attention from scholars at home and abroad in recent years as a new type of energy storage device. However, in the process of use, temperature changes will lead to the occurrence of thermal stresses, which may cause structural failure under multiple cycles. In this paper, the thermal-stress coupled model of structural batteries was established first using the temperature and thermal stress models of structural batteries, considering the heat exchange with the external environment of structural batteries. Then based on the coupled model, the thermal stress in the structural battery was simulated and analyzed in COMSOL considering different charge and discharge rates and ambient temperatures of the structural batteries. The results show that: (1) The higher the charging and discharging rates, the higher the temperature of the structural battery, resulting in greater thermal stress. (2) The higher the ambient temperature of the structural battery, the longer its discharge time and the lower the voltage at which discharge terminates, which is beneficial for the electrochemical performance of the battery. But the higher the ambient temperature, the greater the temperature change inside the structural battery, which is not conducive to the mechanical performance of the structural battery. This study can provide reference for the safety analysis of structural batteries in thermal environments.
Matrix Mechanics of a Particle in a One-Dimensional Infinite Square Well
Authors: Vedral Vlatko
Published: March 2024

We solve the infinite-potential well problem using the method of Heisenberg’s matrix mechanics. In addition to being of educational value, the matrix mechanics allows us to deal with various unphysical issues caused by this potential in a seemingly unproblematic fashion. We also show how to treat many particles within this representation.
On the Success Probability of Quantum Order Finding
Authors: Ekerå Martin
Published: March 2024

We prove a lower bound on the probability of Shor’s order-finding algorithm successfully recovering the order 
r
in a single run. The bound implies that by performing two limited searches in the classical post-processing part of the algorithm, a high success probability can be guaranteed, for any 
r
, without re-running the quantum part or increasing the exponent length compared to Shor. Asymptotically, in the limit as 
r
tends to infinity, the probability of successfully recovering 
r
in a single run tends to one. Already for moderate 
r
, a high success probability exceeding e.g. 1 - 10
-4
can be guaranteed. As corollaries, we prove analogous results for the probability of completely factoring any integer 
N
in a single run of the order-finding algorithm.
Fighting Fire with Fire: Can ChatGPT Detect AI-generated Text?
Authors: Bhattacharjee Amrita , Liu Huan
Published: March 2024

Large language models (LLMs) such as ChatGPT are increasingly being used for various use cases, including text content generation at scale. Although detection methods for such AI-generated text exist already, we investigate ChatGPT's performance as a detector on such AI-generated text, inspired by works that use ChatGPT as a data labeler or annotator. We evaluate the zeroshot performance of ChatGPT in the task of human-written vs. AI-generated text detection, and perform experiments on publicly available datasets. We empirically investigate if ChatGPT is symmetrically effective in detecting AI-generated or human-written text. Our findings provide insight on how ChatGPT and similar LLMs may be leveraged in automated detection pipelines by simply focusing on solving a specific aspect of the problem and deriving the rest from that solution. All code and data is available at https://github.com/AmritaBh/ChatGPT-as-Detector.
Investigation of Polisher Head and Slurry Sweep Effect in Oxide Film Polishing
Authors: Liu Pengzhan , Kang Chul , Park Kihong , Jeon Sanghuck , Wang Ziyang , Lee Hyeonjeong , Jeong Hyunjin , Lee Euihaeng , Kim Taesung
Published: March 2024

Chemical mechanical polishing (CMP) has undergone rapid advancements in global and local planarization. The synergy between the process control and the consumables is critical to overall CMP performance. In addition to optimizing consumables and equipment including a polisher, metrology, and inspection, the polishing protocol plays a crucial role in effective process management. In fabrication scenarios, protocol revision is a convenient and practical approach for problem-solving. This research focuses on the study of head sweep direction, head sweep distance, and slurry sweep effects in oxide film polishing. Sweeping toward the outside resulted in an average increase of 12.66% removal amount for ceria and 11.57% for silica compared to fixed head polishing. Moreover, a longer head sweep distance reduced non-uniformity. While the slurry sweep exhibited a non-significant effect on the removal amount, it proved valuable in optimizing the removal amount profile.
Utilizing a medical school outreach program to help high school students explore the impact of food security and ultraprocessed foods on health risks
Authors: Kemp Kyeorda , Lewis Brianne , Naik Akshata R. , Uhley Virginia E.
Published: March 2024

We describe how we integrated guided learning teaching modules in an enrichment program for high school students with the aim of enhancing their knowledge and skills to empower them to take charge of their own health risks and well-being.
Regulation of the water channel aquaporin-2 by cullin E3 ubiquitin ligases
Authors: Murali Sathish K. , McCormick James A. , Fenton Robert A.
Published: March 2024

Aquaporin 2 (AQP2) is essential for body water homeostasis and is regulated by the antidiuretic hormone vasopressin. The posttranslational modification ubiquitylation is a key regulator of AQP2 abundance and plasma membrane localization. Here we demonstrate that cullin-RING E3 ligases play a vital role in mediating some of the effects of vasopressin to increase AQP2 abundance and plasma membrane accumulation. The results suggest that manipulating cullin activity could be a novel strategy to alter kidney water handling.
Cardiovascular Disease Burden in Persons with Mental Illness: Comparison between a U.S. Psychiatry Outpatient Sample and a U.S. General Population Sample
Authors: Dhingra Radha , He Fan , Saunders Erika F. H. , Waschbusch Daniel A. , Pearl Amanda M. , Bixler Edward O. , Greaney Jody L. , Swigart Alison R. , Al-Shaar Laila , Chinchilli Vernon M. , Yanosky Jeff D. , Liao Duanping
Published: March 2024

Background. Cardiovascular disease (CVD) and depression are the leading causes of disability in the U.S. Using electronic health record data, we describe the CVD burden among persons with mental illness enrolled in the Penn State Psychiatry Clinical Assessment and Rating Evaluation System (PCARES) Registry between 2015 and 2020. Methods. CVD burden assessment included prevalence of CVD conditions (any major CVD or individual CVD risk factors), indicated medication prescriptions for CVD risk factors, and mean levels of body mass index (BMI, kg/m2), glycosylated hemoglobin (HbA1C, %), glucose (mg/dl), and lipids (mg/dl). We compared the CVD burden between the PCARES sample to a representative sample of adults from the U.S. general population (NHANES 2013‐2016) using one‐sample chi‐square/t‐tests for proportions/means. The CVD burden in NHANES participants was adjusted to PCARES age, race, and sex statistics. Results. The PCARES sample (N = 3556) had a mean (SE) age of 42.4 (0.3) years and comprised 63.0% women, 85.0% non‐Hispanic Caucasians, and 41.0% with major depressive disorder. CVD burden was higher in the PCARES sample compared to NHANES participants for any major CVD (8.6% vs. 4.6%), diabetes (18.4% vs. 10.4%), BMI (30.3 vs. 28.3), HbA1C (6.1 vs. 5.6), cholesterol (185.6 vs. 181.7), triglycerides (153.3 vs. 136.1), and indicated antihypertensive (94.3% vs. 76.9%) and cholesterol‐lowering (49.5% vs. 36.7%) medications (Bonferroni‐corrected p = 0.03 for each outcome). The CVD burden was lower in the PCARES sample compared to NHANES participants for hypertension (45.9% vs. 50.4%), dyslipidemia (43.2% vs. 61.9%), HDL‐C (48.4 vs. 41.4), and LDL‐C (107.9 vs. 112.0) (Bonferroni‐corrected p = 0.03 for each outcome). Glucose levels (110.9 vs. 111.9) and indicated antidiabetic medications (87.4% vs. 86.6%) were similar in the two samples (p > 0.05). Conclusions. The CVD burden was higher in persons with mental illness compared to the U.S. general population. Integrated mental and physical healthcare services could reduce long‐term disability among persons with mental illness.
Recycling of Polycarbonate/Acrylonitrile Butadiene Styrene Blends with Flame Retardant Additives for 3D Printing Filament
Authors: Zegeye Lejalem Haile , Atalie Desalegn
Published: March 2024

Recycling waste from electrical and electronic equipment (WEEE) for valuable materials is a critical aspect of the circular economy and sustainable waste management. Recycling these solid wastes into value‐added products is one method for reducing landfill waste and pollution. The purpose of this research was to investigate the recyclability of plastic wastes of Polycarbonate Acrylonitrile Butadiene Styrene blends with Brominated Flame‐Retardant additives (PC‐ABS‐FR). Two types of plastic wastes, PC‐ABS‐FR (GL) and PC‐ABS‐FR (DB), were collected and converted into polymer chips using a mechanical process. To study the effectiveness of waste recyclability, 3D printing filaments were produced through the extrusion process. Chemical elements, functional groups, and thermal and mechanical properties of recycled products were evaluated using EDX, FTIR, DSC, and universal tensile testing equipment, respectively. TGA, cone calorimetry, and melt flow index analyses were also carried out. The results showed that recycled PC‐ ABS–FR (GL) waste‐based filament samples had better thermal and mechanical properties. On the contrary, PC‐ ABS–FR (DB) waste recyclability was not effective in filament extrusion. The mechanical properties of the 3D printing filaments produced from PC‐ABS‐FR electronic waste were found to be similar to those observed in commercially available and previously reported filaments. The strength, thermal property, cross‐sectional homogeneity, and filament diameter of 1.8 ± 0.03 mm of the 3D printer filament made from PC‐ ABS–FR (GL) were suitable for 3D printing applications such as children’s toys, dust bins, and flower vases.
SNHG12 Promotes Autophagy by Blocking the mTOR-Primary Cilia-mTOR Loop via Activating the miR-181a-5p/miR-138-5p-INPP5E Axis in Chondrocyte
Authors: Feng Weijia , Liu Lei , Sha Lin , Wu Zhenkai , Ding Jing
Published: March 2024

Diseases related to cartilage abnormalities pose a serious threat to human health. Normal cartilage contains only one type of cell, chondrocytes. This study aims to investigate the impact of inositol polyphosphate-5-phosphatase E (INPP5E) on chondrocytes and its underlying mechanisms. Following transfection of small interfering RNA INPP5E into chondrocytes, real-time quantitative PCR (RT-PCR) and western blot (WB) assays were conducted to detect the expression of intraflagellar transport 88 (IFT88), Bcl-2-interacting protein 1 (Beclin1), microtubule-associated protein 1 light chain 3 alpha (MAP1LC3A), microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), collagen type II alpha 1 chain (COL2A1), and cyclin D1 (CCND1). Furthermore, immunofluorescence was used to detect the expression of acetylated α-tubulin and microtubule-associated protein 1 light chain 3 (LC3) II. RT-PCR, WB, and the dual luciferase assay demonstrated the regulation between SNHG12, hsa-miR-181a-5p, hsa-miR-138-5p, and INPP5E. Functional recovery experiments were used to observe the regulation of these factors on IFT88, Beclin1, LC3 I, LC3 II, p-PI3K, p-Akt, p-mTOR, collagen II, and cyclin D1 in chondrocytes. The results showed that silencing INPP5E inhibited the mRNA and protein expressions of the investigated factors in chondrocytes. SNHG12 promoted INPP5E expression by inhibiting hsa-miR-181a-5p or hsa-miR-138-5p, which resulted in regulation of the expression of various factors via the hsa-miR-181a-5p/hsa-miR-138-5p-INPP5E axis in chondrocytes. These findings provide a theoretical basis for the treatment of patients with cartilage-related abnormalities.
Piloting Eyes on the Baby: A Multiagency Training and Implementation Intervention Linking Sudden Unexpected Infant Death Prevention and Safeguarding
Authors: Ball Helen L. , Grieve Laura M. , Keegan Alice-Amber , Cooper Louise , Lovell-Kennedy Sophie , Newbury-Birch Dorothy , Cleghorn Nicola , Healy Amanda
Published: March 2024

We describe the coproduction, pilot implementation, and user evaluation of an evidence‐based training intervention addressing prevention of Sudden Unexpected Deaths in Infancy (SUDI) for the multiagency workforce supporting vulnerable families with babies in a northern English county. We aimed in this pilot study to improve knowledge, skills, and engagement of professionals and support staff providing services for vulnerable families with increased risk of SUDI. The training intervention was co‐produced by the academic team and the project Steering Committee which comprised senior leaders from the local authority, health and care sectors, and third‐sector organisations, and rolled out to multiagency teams between November 2022 and March 2023. Evaluation data were collected using a post‐training questionnaire, followed up by the Normalisation Process Theory (NPT) NoMAD survey issued at two time‐points post‐training, and interviews with stakeholders. The evaluation, conducted from January to May 2023, aimed to assess how well the multiagency workforce accepted SUDI prevention as part of their remit and incorporated SUDI prevention activities into their everyday work. Most multiagency professionals and support staff were enthusiastic about the training and their role in SUDI prevention. Fewer health professionals completed the training than expected. Forty percent (397/993) of invited staff completed the training. Our results revealed initial lack of knowledge and confidence around SUDI prevention and targeted provision for vulnerable families which improved following the Eyes on the Baby training. The proportion of nonhealth professionals rating their knowledge of SUDI prevention as good or excellent increased significantly from 28% before training to 57% afterwards. Self‐rated confidence in discussing SUDI prevention with families increased significantly from 71% to 97%. Health professionals’ ratings increased significantly for knowledge from 62% to 96%, and confidence from 85% to 100%. Use of NPT allowed us to identify that by the time of evaluation, the earliest adopters were cognitively involved with the programme and engaged in collective action, while later adopters had not yet reached this stage. We conclude that effective implementation of multiagency working for SUDI prevention can be accomplished by providing clear training and guidance for all staff who have regular or opportunistic contact with vulnerable families. Our next step is to evaluate the sustainability of MAW SUDI prevention over the medium to long term and assess the responses of recipient families to this approach.
Symptoms and Severity of COVID-19 in Patients with Immune-Mediated Inflammatory Diseases: Experience of a University Medical Center
Authors: Schlosser Tobias , Krasselt Marco , Elsing Louis , Hecker Martin , Holler Babett , Hoffmeister Albrecht
Published: March 2024

Background. The pandemic situation of the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) and its associated disease (coronavirus disease 2019 (COVID-19)) represents a challenging condition with a plethora of aspects. The course of COVID-19 in patients with immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD) and rheumatic diseases (RD) is not well known. Our study is one step toward closing this gap by collecting data on vaccination rates, infection-free survival, and individual symptom severity. Methods. We conducted a prospective questionnaire-based study between April 2022 and October 2022 at our university hospital. Outward patients over the age of 18 years were screened for participation and reported about their infection/infection-free survival since the start of the pandemic. Results. Finally, 156 patients were included in the study, 117 (75.0%) of which had inflammatory bowel disease and 39 (25.0%) patients with rheumatic disease. Altogether, 143 (91.7%) persons had received at least one vaccination against SARS-CoV-2. A total of 153 patients provided information regarding their COVID-19 history: 81 patients (52.0%) self-reported about their SARS-CoV-2 infection. In general, courses of infection were mild: only two patients (2.5% of patients with reported COVID-19) were hospitalized due to COVID-19 with one (1.2%) of the two needing intensive care. Asymptomatic COVID-19 had been described by 7 persons (8.6% of patients with reported COVID-19). Acute COVID-19 was accompanied by fatigue/tiredness in 58 persons (71.6% of patients with history of COVID-19) as the most frequent symptom. Other complaints were common cold (55 patients = 67.9%), cough (51 patients = 63.0%), headache (44 patients = 54.3%), and fever (35 patients = 43.2%). Stratified by vaccination status (unvaccinated vs. at least once vaccinated), the time to infection differed significantly (logrank test: p=0.04, Chi2 4.1). At least once vaccinated people had a median COVID-19-free survival of 28.5 months (confidence interval (CI): 23.6 months-not reached). Without any vaccination, the estimated time to infection was 25.1 months (CI: 23.6 months-not reached). Conclusion. Our IMID patients have a high rate of vaccination against SARS-CoV-2. Data show a significantly longer infection-free survival in vaccinated IMID patients as compared to unvaccinated patients. Discrimination between symptoms of COVID-19 and a concomitant inflammatory disease is difficult as complaints might be overlapping. This trial is registered with DRKS00028880.
Efficient Bioelectrochemical Cell Generation and Green Synthesis of Silver Nanoparticles Using Pomegranate and Pineapple Peel Extracts: A Comprehensive Characterization Study
Authors: Mehrin Shamima , Tanisa Nilufer Yesmin , Awal Rabiul , Alam Khan Md. Kamrul , Shaqur Abdus , Ahmed Shamim , Islam Shahidul , Mia Asad
Published: March 2024

The present study investigates an environmentally conscious method for synthesizing silver nanoparticles (AgNPs) by employing extracts from pomegranate peel (PgP) and pineapple peel (PnP). This green synthesis approach offers a sustainable alternative to traditional chemical methods, thereby reducing the ecological footprint associated with nanoparticle production. The PgP and PnP extracts serve as both reducing and capping agents during the synthesis process, enhancing the biocompatibility of the resultant AgNPs. Various characterization techniques, including UV-Vis spectroscopy, Raman analysis, X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared (FTIR), and transmission electron microscopy (TEM), were utilized to analyze the synthesized AgNPs. UV-Vis spectroscopy confirmed the formation of AgNPs through characteristic surface plasmon resonance peaks, while FTIR examined the interaction between biomaterial components and the oxidation and coating of silver nanoparticles. Raman analysis elucidated the functional groups responsible for reducing and stabilizing AgNPs, while XRD provided insights into their crystalline structure. TEM images revealed the size and morphology of the nanoparticles, while DLS characterized their average size and morphology. In addition, the synthesized AgNPs were utilized in a bioelectrochemical cell to leverage their unique properties for enhanced electrochemical performance, showcasing their potential application in energy storage and conversion systems. Overall, this study demonstrates the feasibility of utilizing agricultural waste products such as PgP and PnP for sustainable AgNP synthesis, offering promising prospects for environmentally friendly nanotechnology advancement.
Chemical Profiling and Biological Activities of Ziziphus Mauritiana var. spontanea (Edgew.) R.R. Stewart ex Qaiser & Nazim. and Oenothera Biennis L.
Authors: Ambrin Ambrin , Adil Muhammad , Filimban Faten Zubair , Naseer Muhammad
Published: March 2024

Bioactive compounds of medicinal plants, including polyphenols, flavonoids, terpenoids, and alkaloids, are essential sources for developing analgesic, anti-inflammatory, and antidiarrheal drugs. In the current study, secondary metabolites were assessed through phytochemical screening and GC-MS analysis whereas analgesic activity was carried out through hot plate (HP) and acetic acid-induced method (AAI), anti-inflammatory through paw edema model (PEM), and antispasmodic activity via charcoal meal test (CMT) using ethyl acetate and ethanolic extract of Ziziphus mauritiana var. spontanea and Oenothera biennis. The phytochemical screening revealed that the ethyl acetate and ethanolic extracts of Z. mauritiana and O. biennis were rich in alkaloids, flavonoids, tannins, steroids, triterpenoids, and saponins. GC-MS analysis of Z. mauritiana and O. biennis of ethyl acetate and ethanolic extract showed the existence of many bioactive substances at various retention durations (min). These included pharmacologically active compounds such as heptadecane, 2-methoxy-4-vinylphenol, hexadecanoic acid, and tetradecanoic acid. The results of the HP method revealed that ethanolic and ethyl acetate extracts of Z. mauritiana and O. biennis at 300 mg/kg increased basal reaction time significantly (p<0.001) after 90 min. The results of the AAI method revealed that the ethanolic and ethyl acetate extract of Z. mauritiana and O. biennis showed significant (p<0.001) peripheral analgesic activity at the dose of 200 and 300 mg/kg body weight. The dosage of 100, 200, and 300 mg/kg body weight of the ethyl acetate and ethanolic extracts of Z. mauritiana and O. biennis showed significant (p<0.001) anti-inflammatory activity. According to PEM, the ethanolic extract of O. biennis showed the highest reduction in paw volume (73.3%) at 300 mg/kg. The results of CMT revealed that ethanolic and ethyl acetate extract of Z. mauritiana and O. biennis significantly (p<0.001) inhibited charcoal movement at 300 mg/kg. The maximum percent inhibition (67.2%) was shown by ethyl acetate of O. biennis at 300 mg/kg. From the present study, it can be concluded that ethanolic and ethyl acetate extracts of Z. mauritiana and O. biennis have the potential to manage inflammation, pain, and diarrhea-related problems mainly at a higher dose, i.e., 300 mg/kg. The presence of alkaloids, flavonoids, tannins, steroids, triterpenoids, and saponins might be among the responsible bioactive constituents. These plants showed significant medicinal and therapeutic efficacy which are novel. However, further studies are required to investigate the mechanism responsible for the activity.
Nitrosyl-heme and Heme Iron Intake from Processed Meats and Risk of Colorectal Cancer in the EPIC-Spain Cohort
Authors: Rizzolo-Brime Lucía , Lujan-Barroso Leila , Farran-Codina Andreu , Bou Ricard , Lasheras Cristina , Amiano Pilar , Aizpurua Amaia , Sánchez Maria-Jose , Molina-Montes Esther , Guevara Marcela , Moreno-Iribas Conchi , Gasque Alba , Chirlaque-López María Dolores , Colorado-Yohar Sandra M. , Huerta José María , Zamora-Ros Raul , Agudo Antonio , Jakszyn Paula
Published: March 2024

Background:

The International Agency for Research on Cancer classified processed meats (PM) as “carcinogenic” and red meat as “probably carcinogenic” for humans. The possible relationship between colorectal cancer risk and the mechanisms involved in the carcinogenesis of PMs have not been established yet. Nitrosyl-heme and heme iron have been proposed as potential-related compounds. The aim of this study was to determine the association between nitrosyl-heme and heme iron intake and colorectal cancer risk among participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain study.

Methods:

This prospective study included 38,262 men and women from the EPIC-Spain study. Food consumption was assessed using diet history and food composition tables. Heme iron and nitrosyl-heme intake were determined by estimating the intake of PM items and conducting laboratory analyses. HR estimates were obtained by proportional hazard models, stratified by age at recruitment and study center and adjusted for sex, total energy intake, education, smoking, body mass index, waist size, physical activity, lifetime alcohol, fibre, calcium, and familiar colorectal cancer history.

Results:

During a mean follow-up of 16.7 years, 577 participants were diagnosed with colorectal cancer. We found no overall association between nitrosyl-heme [HRT3vsT1, 0.98; 95% confidence interval (CI), 0.79–1.21] or heme iron intakes (HRT3vsT1, 0.88; 95% CI, 0.70–1.10) with colorectal cancer risk, nor according to tumor subtypes.

Conclusions:

Our study found no evidence supporting a link between nitrosyl-heme or heme iron intake and colorectal cancer risk in Spanish subjects.

Impact:

As research on nitrosyl-heme is preliminary, more heterogeneous studies are necessary to provide more convincing evidence on their role in colorectal cancer carcinogenesis.
Safety, Efficacy, and Biological Data of T-Cell–Enabling Oncolytic Adenovirus TILT-123 in Advanced Solid Cancers from the TUNIMO Monotherapy Phase I Trial
Authors: Pakola Santeri A. , Peltola Katriina J. , Clubb James H.A. , Jirovec Elise , Haybout Lyna , Kudling Tatiana V. , Alanko Tuomo , Korpisaari Riitta , Juteau Susanna , Jaakkola Marjut , Sormunen Jorma , Kemppainen Jukka , Hemmes Annabrita , Pellinen Teijo , van der Heijden Mirte , Quixabeira Dafne C.A. , Kistler Claudia , Sorsa Suvi , Havunen Riikka , Santos Joao M. , Cervera-Carrascon Victor , Hemminki Akseli
Published: March 2024

Purpose:

TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cytotoxicity in solid tumors.

Patients and Methods:

TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial designed to assess the safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123. The primary endpoint was safety by adverse events (AE), laboratory values, vital signs, and electrocardiograms. Secondary endpoints included tumor response, pharmacokinetics, and predictive biomarkers.

Results:

Twenty patients were enrolled, with a median age of 58 years. Most prevalent cancer types included sarcomas (35%), melanomas (15%) and ovarian cancers (15%). No dose-limiting toxicities were observed. The most frequent treatment-related AEs included fever (16.7%), chills (13.0%), and fatigue (9.3%). Ten patients were evaluable for response on day 78 with RECIST 1.1, iRECIST or PET-based evaluation. The disease control rate by PET was 6/10 (60% of evaluable patients) and 2/10 by RECIST 1.1 and iRECIST(20%of evaluable patients). Tumor size reductions occurred in both injected and non-injected lesions. TILT-123 was detected in injected and non-injected tumors, and virus was observed in blood after intravenous and intratumoral injections. Treatment resulted in reduction of lymphocytes in blood, with concurrent lymphocyte increases in tumors, findings compatible with trafficking.

Conclusions:

TILT-123 was safe and able to produce antitumor effects in local and distant lesions in heavily pre-treated patients. Good tolerability of TILT-123 facilitates combination studies, several of which are ongoing (NCT04217473, NCT05271318, NCT05222932, and NCT06125197).

See related commentary by Silva-Pilipich and Smerdou, p. 3649
FIGURE 7 from MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases
Authors: Ito Koichi , Harada Ibuki , Martinez Criseyda , Sato Katsutoshi , Lee EunJee , Port Elisa , Byerly Jessica H. , Nayak Anupma , Tripathi Ekta , Zhu Jun , Irie Hanna Y.
Published: March 2024

MARCH2 suppresses metastases of TNBC cells. A, Metastatic lung colonization by MDA-MB-231/Luciferase cells expressing vector control, WT MARCH2, or RING domain–mutant (W97A) MARCH2 following tail vein injection was serially assessed by IVIS imaging. Total photons/second in a 3.3 × 3.3 cm2 area around the lung area of each mouse was used for statistical analysis. P values were calculated by Student t test, and the P value less than 0.05 was regarded as statistically significant (*, P < 0.05; **, P < 0.01; ***, P < 0.001). Data represent mean ± SD. B, Spontaneous metastases formation in the lungs by MDA-MB-231/LM2-4/Luciferase cells expressing vector control or WT MARCH2 following implantation into left fourth mammary fat pad implantation was serially assessed by IVIS imaging. Total photons/second in a 3.3 × 3.3 cm2 area around the upper body area of each mouse was used for statistical analysis. P values were calculated by Student t test. Data represent mean ± SD.
FIGURE 2 from MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases
Authors: Ito Koichi , Harada Ibuki , Martinez Criseyda , Sato Katsutoshi , Lee EunJee , Port Elisa , Byerly Jessica H. , Nayak Anupma , Tripathi Ekta , Zhu Jun , Irie Hanna Y.
Published: March 2024

PTK6 inhibition increases ubiquitination and degradation of SNAIL in TNBC. A, PTK6 inhibitor (P21d) treatment or PTK6 shRNA downregulates SNAIL in TNBC cells. Human MDA-MB-231 or mouse MMTV-myc cells were treated with P21d for 24 hours and SNAIL expression was assessed by Western blot analysis. Lysates of MDA-MB-231 cells expressing vector control or either of two independent PTK6 shRNA vectors were assessed for SNAIL expression. B, MDA-MB-231 cells overexpressing HA-ubiquitin and Flag-SNAIL were treated with P21d for 8 hours with MG132 cotreatment for the last 4 hours. Lysates were immunoprecipitated with anti-FLAG antibody and probed with anti-HA or FLAG antibody. The result is representative of three independent experiments. C, Representative images of Duolink PLA using MDA-MB-231 cells coexpressing HA-ubiquitin and Flag-SNAIL. Cells were treated with P21d (5 µmol/L) for 24 hours with MG132 cotreatment for the last 4 hours and incubated with antibodies against HA (Ubiquitin) and FLAG (SNAIL) for PLA (red) and Phalloidin for F-actin and counterstaining. PLA signals (red)/cell were quantitated using ImageJ (left). Scale bar, 15 µm. D, Representative images of PLA using MDA-MB-231 cells overexpressing HA-ubiquitin only. Cells were treated with P21d for 24 hours and with MG132 cotreatment for the last 4 hours and incubated with antibodies against HA (Ubiquitin) and SNAIL for PLA (red) and Phalloidin for F-actin counterstaining. PLA signals/cell were quantitated using ImageJ (left). Scale bar, 15 µm. E, Representative images of PLA using MDA-MB-231 cells overexpressing HA-ubiquitin only that were transfected with control or PTK6 siRNA for 48 hours. Cells were treated with MG132 for the last 4 hours and incubated with antibodies against HA (Ubiquitin) and SNAIL for PLA (red) and Phalloidin for F-actin counterstaining. PLA signals/cell were quantitated using Image (left). Scale bar, 15 µm. All the PLA signals were counted by ImageJ with a fixed setting. Data represent mean ± SEM. *, P = 0.05; ***, P = 0.0001 by Student t test.
FIGURE 1 from MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases
Authors: Ito Koichi , Harada Ibuki , Martinez Criseyda , Sato Katsutoshi , Lee EunJee , Port Elisa , Byerly Jessica H. , Nayak Anupma , Tripathi Ekta , Zhu Jun , Irie Hanna Y.
Published: March 2024

Expression of SNAIL and PTK6 in TNBC. A, Prognostic significance of SNAIL expression in TNBC. KM survival curves of SNAIL expression in patients with TNBC (defined as estrogen receptor, progesterone receptor, and HER2 negative) using the METBRIC dataset (n = 290) and KM plotter (n = 734). SNAIL expression was divided along the median into low versus high expressors. B, Representative images of IHC staining for PTK6 and SNAIL expression in TNBC tissue microarray (n = 48). Low (0, 1+) and high (2+, 3+) expression was scored by two independent reviewers. C, Expression of PTK6 and SNAIL in triple-negative PDX tumors.