bluuebunny/crossref_metadata_2025 huggingface dataset:
Pentaquark molecular states with hidden bottom and double strangeness
Authors: Song Jing , Duan Man-Yu , Roca Luis , Oset Eulogio
Published: October 2024

We investigate the meson-baryon interaction in coupled channels with the quantum numbers of the pentaquarks $$P_{bss}$$

P

bss

and $$P_{bsss}$$

P

bsss

. The interaction is derived from an extension of the local hidden gauge approach to the heavy quark sector, which has demonstrated accurate results compared to experiments involving $$\Omega _{b}$$

Ω
b

, $$\Xi _{b}$$

Ξ
b

states, and pentaquarks $$P_{c}$$

P
c

and $$P_{cs}$$

P

cs

. In our study, we identify several molecular states with small decay widths within the chosen set of coupled channels. The spin-parity ($$J^P$$

J
P

) of these states is as follows: $$J^P={\frac{1}{2}}^-$$

J
P

=

1
2

-

for pseudoscalar-baryon ($${\frac{1}{2}}^+$$

1
2

+

) coupled channels, $$J^P={\frac{3}{2}}^-$$

J
P

=

3
2

-

for pseudoscalar-baryon ($${\frac{3}{2}}^+$$

3
2

+

) coupled channels, $$J^P={\frac{1}{2}}^-$$

J
P

=

1
2

-

and $${\frac{3}{2}}^-$$

3
2

-

for vector-baryon ($${\frac{1}{2}}^+$$

1
2

+

) coupled channels, and $$J^P={\frac{1}{2}}^-$$

J
P

=

1
2

-

, $${\frac{3}{2}}^-$$

3
2

-

, $${\frac{5}{2}}^-$$

5
2

-

for vector-baryon ($${\frac{3}{2}}^+$$

3
2

+

) coupled channels. We search for the poles of these states and evaluate their couplings to the different channels.
Effective Pest Control Through Natural Predators: A Dynamical Plant–Pest–Predator Model
Authors: Shivam  , Singh Teekam , Kumar Mukesh , Singh Kamred Udham , Barik Mamta , Chauhan Sudipa
Published: October 2024

The impact of pests on crop yield is a significant worry for farmers, and finding an effective strategy to control insect population growth has become a pressing matter. This study explores the dynamic analysis of a model that incorporates natural predators to control crop pests. In the research, an analysis is conducted on the model’s positivity and boundedness, followed by an examination of the existence and stability of the equilibrium points. The study focused on analyzing bifurcations at a biologically feasible equilibrium point. The parameters considered for bifurcation are the predation rate by pests and the consumption rate of natural predators. In addition, an optimal control technique has been employed to enhance the growth of the plant population through the utilization of Pontryagin’s maximum principle. Moreover, the impact of the nine parameters on the model is examined through sensitivity analysis using the partial rank correlation coefficient method. Numerical simulations are conducted to validate the analytical findings, revealing the occurrence of bifurcation and the positive impact of control on plant population growth.
Multiple episodes of late Neoproterozoic rifting in the Tarim Craton during its separation from the supercontinent Rodinia
Authors: Wang Caiyun , Wu Hongxiang , Dilek Yildirim , Zhang Fengqi , Chen Hanlin , Li Feng , Qiu Duwei , Shi Xuhua , Lin Xiubin , Cheng Xiaogan
Published: October 2024

In this paper, we review and evaluate the magmatic history, regional stratigraphy, structural patterns and sedimentary provenance features of the Late Neoproterozoic Tarim Craton to elucidate the nature and different modes of extensional tectonics during the Latest Neoproterozoic, a critical time coinciding with the disintegration of the supercontinent Rodinia. New detrital zircon U–Pb ages and geochemical data acquired from quartz schists and spatially associated granites in the Tugerming anticline along the northern margin of the Tarim Craton have revealed Cryogenian ages, as opposed to Early Neoproterozoic and older ages as reported in previous studies. Granitic intrusions are dated at 656–637 Ma, which involved remelting of the ancient crust following the decline of the initial (Cryogenian) rift stage. They are unconformably overlain by terrestrial clastic deposits. Based on the available detrital zircons from the Late Neoproterozoic sedimentary rock assemblages, we identify a major change in the provenance of the basinal strata at the end of the Cryogenian period. This inferred provenance change, associated with basement exhumation, overlaps in time with resumed magmatic activities, basin inversion and uplift along the northern margin of the craton. The initial, Cryogenian rifting stage was facilitated by pure shear deformation that produced rift basins in and across the Tarim Craton. The subsequent rifting stage was facilitated by simple shear deformation, confined to the northern edge of the craton as the break-up of the supercontinent Rodinia further progressed. Episodic rifting of the Tarim Craton and its separation from Rodinia were aided by thermal weakening of its lithosphere owing to the periodic impingement of mantle upwelling beneath it throughout the Cryogenian and Ediacaran periods.
A Unified Framework for Multi-Domain CTR Prediction via Large Language Models
Authors: Fu Zichuan , Li Xiangyang , Wu Chuhan , Wang Yichao , Dong Kuicai , Zhao Xiangyu , Zhao Mengchen , Guo Huifeng , Tang Ruiming
Published: October 2024

Multi-Domain Click-Through Rate (MDCTR) prediction is crucial for online recommendation platforms, which involves providing personalized recommendation services to users in different domains. However, current MDCTR models are confronted with the following limitations. Firstly, due to varying data sparsity in different domains, models can easily be dominated by some specific domains, which leads to significant performance degradation in other domains (i.e., the “seesaw phenomenon”). Secondly, when new domain emerges, the scalability of existing methods is limited, making it difficult to adapt to the dynamic growth of the domain. Traditional MDCTR models usually use one-hot encoding for semantic information such as product titles, thus losing rich semantic information and leading to insufficient generalization of the model. In this paper, we propose a novel solution Uni-CTR to address these challenges. Uni-CTR leverages Large Language Model (LLM) to extract layer-wise semantic representations that capture domain commonalities, mitigating the seesaw phenomenon and enhancing generalization. Besides, it incorporates a pluggable domain-specific network to capture domain characteristics, ensuring scalability to dynamic domain growth. Experimental results on public datasets and industrial scenarios show that Uni-CTR significantly outperforms state-of-the-art (SOTA) models. In addition, Uni-CTR shows significant results in zero shot prediction. Code is available at
https://anonymous.4open.science/r/multi-domain
.
A Comprehensive Survey on Rare Event Prediction
Authors: Shyalika Chathurangi , Wickramarachchi Ruwan , Sheth Amit P.
Published: October 2024

Rare event prediction involves identifying and forecasting events with a low probability using machine learning (ML) and data analysis. Due to the imbalanced data distributions, where the frequency of common events vastly outweighs that of rare events, it requires using specialized methods within each step of the ML pipeline, that is, from data processing to algorithms to evaluation protocols. Predicting the occurrences of rare events is important for real-world applications, such as Industry 4.0, and is an active research area in statistical and ML. This article comprehensively reviews the current approaches for rare event prediction along four dimensions: rare event data, data processing, algorithmic approaches, and evaluation approaches. Specifically, we consider 73 datasets from different modalities (i.e., numerical, image, text, and audio), four major categories of data processing, five major algorithmic groupings, and two broader evaluation approaches. This article aims to identify gaps in the current literature and highlight the challenges of predicting rare events. It also suggests potential research directions, which can help guide practitioners and researchers.
An Unbiased Risk Estimator for Partial Label Learning with Augmented Classes
Authors: Hu Jiayu , Shu Senlin , Li Beibei , Xiang Tao , He Zhongshi
Published: October 2024

Partial Label Learning (PLL) is a typical weakly supervised learning task, which assumes each training instance is annotated with a set of candidate labels containing the ground-truth label. Recent PLL methods adopt identification-based disambiguation to alleviate the influence of false positive labels and achieve promising performance. However, they require all classes in the test set to have appeared in the training set, ignoring the fact that new classes will keep emerging in real applications. To address this issue, in this article, we focus on the problem of Partial Label Learning with Augmented Class (PLLAC), where one or more augmented classes are not visible in the training stage but appear in the inference stage. Specifically, we propose an unbiased risk estimator with theoretical guarantees for PLLAC, which estimates the distribution of augmented classes by differentiating the distribution of known classes from unlabeled data and can be equipped with arbitrary PLL loss functions. Besides, we provide a theoretical analysis of the estimation error bound of the estimator, which guarantees the convergence of the empirical risk minimizer to the true risk minimizer as the number of training data tends to infinity. Furthermore, we add a risk-penalty regularization term in the optimization objective to alleviate the influence of the over-fitting issue caused by negative empirical risk. Extensive experiments on benchmark, UCI, and real-world datasets demonstrate the effectiveness of the proposed approach.
P2FTrack: Multi-Object Tracking with Motion Prior and Feature Posterior
Authors: Zhang Hong , Wan Jiaxu , Zhang Jing , Yuan Ding , Li Xuliang , Yang Yifan
Published: October 2024

Multiple object tracking (MOT) has emerged as a crucial component of the rapidly developing computer vision. However, existing multi-object tracking methods often overlook the relationship between features and motion, hindering the ability to strike a performance balance between coupled motion and complex scenes. In this work, we propose a novel end-to-end multi-object tracking method that integrates motion and feature information. To achieve this, we introduce a motion prior generator that transforms motion information into attention masks. Additionally, we leverage prior-posterior fusion multi-head attention to combine the motion-derived priors and attention-based posteriors. Our proposed method is extensively evaluated on MOT17 and DanceTrack datasets through comprehensive experiments and ablation studies, demonstrating state-of-the-art performance in the feature-based method with reasonable speed.
A Systematic Literature Review on Multi-Robot Task Allocation
Authors: K A Athira , J Divya Udayan , Subramaniam Umashankar
Published: October 2024

Muti-Robot system is gaining attention and is one of the critical areas of research when it comes to robotics. Coordination among multiple robots and how different tasks are allocated to different system agents are being studied. The objective of this Systematic Literature Review (SLR) is to provide insights on the recent advancement in Multi-Robot Task Allocation (MRTA) problems emphasizing promising approaches for task allocation. In this study, we collected scientific papers from five different databases for MRTA. We outline the different approaches for task allocation algorithms, classifying them according to the methods, and emphasizing recent advances. In addition, we discuss the function of uncertainty in task allocation and typical coordination techniques utilized in task allocation to identify gaps in the literature and suggest the most promising ones.
Development of a Robotic Device that Performs Head Bunting to Relieve User Tension
Authors: Adachi Yuga , Tanaka Fumihide
Published: October 2024

Inspired by an animal behavior called bunting, in which the animal rubs its head against other objects, including humans, we developed robotic prototypes capable of performing such bunting behaviors. Since physical contact plays an important role in therapeutic interactions between pets and their owners, we hypothesize that robot bunting can have a similar effect on its user. This article reports on the development of such a robot with a flexible neck that can change its stiffness while the robot is rubbing its head against the user. An exploratory study was also conducted with 22 human participants, on whom the developed robot performed head bunting with three different (low/high/variable) stiffness conditions. The results show that the participants’ psychological tension, as measured by the temporary mood scale (TMS), was significantly reduced (p

\(\lt\)

0.001) after interacting with the robot. The difference between the three stiffness conditions was not significant in this study. Due to the lack of a control condition, we cannot confirm a clear effect of the stiffness change; however, some participants commented that the stiffness change made the robot's behavior lifelike and relaxing.
A Very Simple and Feasible Colorimetric-Electrochemical Bimodal Method for H2O2 Detection in Human Serum
Authors: Han Chen-Yang , Wang Kun-Zhi , Chen Xin , Chen Zhencheng , Han Guo-Cheng , Feng Xiao-Zhen , Kraatz Heinz-Bernhard
Published: October 2024

Hydrogen peroxide (H2O2) possesses disinfectant, antiseptic, deodorizing, and cleansing properties. It is commonly used to clean wounds, ulcers, abscessed sinuses, and pus in the ear. Herein, a colorimetric-electrochemical bimodal method for the detection of hydrogen peroxide in serum was constructed, when using a platinum sheet electrode electrocatalyzes H2O2 producing hydroxyl radical, resulting in oxidising TMB and giving a color and current change. After optimaztion, cyclic voltammetry, differential pulse voltammetry and ultraviolet spectrophotometry constituting a colorimetric-electrochemical bimodal method were used to establish four linear relationships within the concentration range of 10.00–1000.00 μM. The limit of detection was found to be 3.33 μM. Additionally, the method’s recoveries ranged from 98.88% to 101.10% with a relative standard deviation of no more than 3.70% when using the standard addition method in serum, which indicates its potential for practical medical testing.
Innate players in Th2 and non-Th2 asthma: emerging roles for the epithelial cell, mast cell, and monocyte/macrophage network
Authors: Kotrba Johanna , Müller Ilka , Pausder Alexander , Hoffmann Aaron , Camp Belinda , Boehme Julia D. , Müller Andreas J. , Schreiber Jens , Bruder Dunja , Kahlfuss Sascha , Dudeck Anne , Stegemann-Koniszewski Sabine
Published: October 2024

Asthma is one of the most common chronic respiratory diseases and is characterized by airway inflammation, increased mucus production, and structural changes in the airways. Recently, there is increasing evidence that the disease is much more heterogeneous than expected, with several distinct asthma endotypes. Based on the specificity of T cells as the best-known driving force in airway inflammation, bronchial asthma is categorized into T helper cell 2 (Th2) and non-Th2 asthma. The most studied effector cells in Th2 asthma include T cells and eosinophils. In contrast to Th2 asthma, much less is known about the pathophysiology of non-Th2 asthma, which is often associated with treatment resistance. Besides T cells, the interaction of myeloid cells such as monocytes/macrophages and mast cells with the airway epithelium significantly contributes to the pathogenesis of asthma. However, the underlying molecular regulation and particularly the specific relevance of this cellular network in certain asthma endotypes remain to be understood. In this review, we summarize recent findings on the regulation of and complex interplay between epithelial cells and the “nonclassical” innate effector cells mast cells and monocytes/macrophages in Th2 and non-Th2 asthma with the ultimate goal of providing the rationale for future research into targeted therapy regimens.
Parenteral nutrition results in peripheral ileal to hepatic circadian discordance in mice
Authors: Shearn Colin T. , Anderson Aimee L. , Devereaux Michael W. , Sokol Ronald J.
Published: October 2024

This study used a novel short-term model of parenteral nutrition (PN) that is translationally relevant. We find that short-term PN is sufficient to induce hepatic and ileal changes in circadian transcription factor expression and to prevent normal concordant coordination of circadian transcription factors between the ileum and liver. These data suggest that targeting circadian transcription may have some clinical benefit in patients receiving parenteral nutrition.
Residual Convolutional Attention Model With Transfer Learning for Detecting Multianomalous Features in Structural Vibration Data
Authors: Li Tao , Zhang Zhongyu , Hou Rui , Zheng Kangkang , Ren Dongwei , Yuan Ruiqi , Jia Xinyu
Published: October 2024

In response to the data anomalies and frequent false alarms caused by harsh environments in long‐term structural health monitoring (SHM), this study has reframed the detection of abnormal vibration data as a time series classification problem. This approach identifies multiple anomalous features, thereby reducing manual detection costs. The novel developed Convolutional Neural Network with Squeeze‐and‐Excitation and Multi‐Head Self‐Attention (CNN–SE–MHSA) employs a deep residual network structure with channel and spatial attention mechanisms, effectively handling the global long‐term dependencies required for anomaly feature learning. It better understands and utilizes feature information across different levels and dimensions, enhancing classification accuracy in complex anomaly situations. Through t‐SNE dimensionality reduction visualization and interpretability analysis, it is demonstrated that the model excels in identifying critical features. Furthermore, by generating simulated data with a variational autoencoder (VAE) and implementing transfer learning strategies based on these data, the issue of low recognition accuracy for complex anomaly data due to data imbalance can be effectively mitigated. In a 25‐day long‐term monitoring experiment of indoor tunnel lining structures, this method demonstrated an average accuracy rate exceeding 96% and a rapid detection capability within 16 min. The results indicate that this method achieves high accuracy in anomaly detection for long‐term monitoring data, even when relying exclusively on time‐domain data.
Performance and Characteristics of Sprayed Flexible Sensor for Strain Monitoring of Steel Bridges
Authors: Zhang Qing-Hua , Chen Jun , Huang Qi-Bin , Shao Shao-Bing , Cui Chuang
Published: October 2024

Monitoring stress and strain at the critical details of steel bridges is essential for ensuring structural integrity. This study introduces a three‐layer flexible strain sensor produced through a spraying process, using flake‐shaped silver‐coated copper powder as the conductive filler and modified acrylic emulsion as the matrix material. The study investigated the impact of size parameters on sensor sensitivity, determining optimal dimensions of 20 mm in length, 2 mm in width, and an initial resistance value ranging from 1.0 Ω to 1.8 Ω. Analysis of the optimized sensor’s performance unveiled high sensitivity and linear response capabilities under low strain conditions with a gauge factor (GF) value of up to 25.6 and a linear correlation coefficient R2 ≥ 0.971 under 300 με. Notably, the sensor exhibits an extremely low strain detection limit of 0.005% and a broad response range spanning from 0.005% to 0.19% strain. It demonstrates swift response and recovery times of 500–800 ms, showcases directional strain response, exhibits good repeatability, and endures durability tests (withstanding 3000 cycles). Furthermore, a fitting formula is proposed to accurately depict the strain and relative resistance change relationship across a wide response range. The study and initial application of this sensor’s sensing characteristics and performance signify its potential for practical engineering applications.
Clinical, Pathologic, and Genetic Spectrum of Collagen VI–Related Disorder in China—A Retrospective Observational Multicenter Study
Authors: Hu Chaoping , Shi Yiyun , Zhao Lei , Zhu Wenhua , Jiao Kexin , Yu Lifei , Li Xihua , Wang Yi
Published: October 2024

Background: Collagen VI‐related disorder (COLVI‐RD) is one of the most common congenital muscular dystrophies. However, data is limited in China.

Methods: We conducted a retrospective study at two tertiary centers. Clinical presentations, lab findings (including serum creatine kinase levels), muscle biopsy, and molecular test results for patients diagnosed with definite COLVI‐RD were collected.

Results: A total of 82 patients were enrolled in the study, including 4 with early–severe Ullrich congenital muscular dystrophy (E–S UCMD) (4.8%), 45 with moderate–progressive Ullrich congenital muscular dystrophy (M–P UCMD, 54.9%), 19 with mild UCMD (23.2%), and 14 with Bethlem myopathy (BM, 17.1%). Feeding difficulty, DDH, and neurogenic damage were more common in E–S and M–P UCMD, while contracture of distal joints, atrophic scars, and hyperkeratosis was more prominent in mild UCMD and BM. Seventy patients harbored 64 pathogenic mutations in COLVI‐related genes: 28 patients in COL6A1 gene, 25 patients in the COL6A2 gene, and 17 patients in the COL6A3 gene, among which 33 mutations were novel. Missense and splicing mutations were predominant for COL6A1 and COL6A3 genes, which were mostly located in N‐terminus of THD, in a dominant pattern, while mutations in the COL6A2 gene were much more polymorphic, which spread throughout the whole length of the gene, in a dominant or recessive pattern. Immunofluorescence dual labeling of Collagen VI/IV in 44 patients showed complete deficiency of Collagen VI in 10 patients (22.7%), sarcolemma‐specific Collagen VI deficiency in 25 patients (56.8%), and normal Collagen VI staining in 9 patients (20.5%).

Conclusion: Our study reported the largest cohort of COLVI‐RD in China, which showed M–P UCMD was the most common phenotype, followed by mild UCMD and BM. We identified 30 novel mutations and expanded the genetic spectrum. Missense and splicing mutations were predominant for COL6A1 and COL6A3 genes, while mutations in the COL6A2 gene were much more polymorphic. For severe phenotypes, most mutations are sporadic, while some are AD or recessive inherited. For milder phenotypes, sporadic and AD inherited were both common, while only 1 patient with recessive mutations was observed.
Serum Neurofilament Light Chain Levels Correlate With Skin Inflammation and Scratch Lesions in Patients With Pruritus
Authors: Mueller Simon M. , Zhu Jie , Brandt Oliver , Navarini Alexander A. , Yaldizli Oezguer , Papadopoulou Athina , Kuhle Jens
Published: October 2024

Background: Neurofilament light chain (NfL) has been identified as a biomarker in neuroaxonal injury. Cutaneous nerve injury resulting from inflammation and/or forced scratching may also potentially affect serum NfL (sNfL) levels.

Objectives: We aimed to explore the relationship between sNfL levels and the severity of skin inflammation and scratch lesions in patients with pruritus.

Methods: In this cross‐sectional pilot study, we measured the sNfL levels of 10 patients with pruritus of different aetiologies, and calculated age‐ and BMI‐adjusted sNfL percentiles based on a normative database consisting of 4532 control individuals. Next, we investigated the relationship between the levels of sNfL and the severity of skin inflammation and scratching injuries in these patients using a newly‐created Skin Inflammation and Scratch Lesions (SISL) score.

Results: A positive correlation was observed between sNfL levels and the severity of skin inflammation and scratch lesions as measured by the SISL score (Spearman’s rho = 0.70, p = 0.031). When correlated separately, both the “skin inflammation only” and “scratch lesions only” scores correlated positively with sNfL levels (Spearman’s rho = 0.68, p = 0.031; Spearman’s rho = 0.66, p = 0.041, respectively).

Conclusions: sNfL may be a potential biomarker for cutaneous nerve injury associated with skin inflammation and/or scratching.
Global Trends in LADA Type Diabetes Research: A Bibliometric Analysis of Publications from Web of Science and Scopus, 1994–2024
Authors: Kudabayeva Khatimya , Tleumagambetova Bibigul , Bazargaliyev Yerlan , Kosmuratova Raikul , Zhylkybekova Aliya
Published: October 2024

The prevalence of T2DM has been increasing dramatically over recent decades, about 537 million people in 2021. LADA type diabetes, a subtype of diabetes that exhibits characteristics of both T2DM and autoimmune beta‐cell destruction similar to T1DM, but with a later onset. The aim of this study is to analyze the main research field on LADA type, including analysis of countries, institutions, journals, authors, and keywords. This research utilized a descriptive bibliometric design. We collected and analyzed data from 672 publications indexed in the Web of Science and Scopus databases, covering the period from 1994 to January 2024. The bibliometric analysis included English‐language research articles that involved studies on patients with LADA type diabetes, aged 18 years or older. RStudio and the Bibliometrix R package were used for data merging and for performing statistical and visual analyses. The annual publication shows an upward trend over the period, with the highest number of publications per year in 2021. The study showed that China leads in the number of articles, with 101 papers published. The United Kingdom demonstrates significant international collaborations, particularly with Germany. The top institutions in terms of the number of published articles are the Norwegian University of Science and Technology in the Kingdom of Norway, followed by the Central South University in China. Tuomi has shown significant long‐term publication impact, while Zhou ranks among the most frequently cited authors. Diabetes Care is one of the most important scientific journals in diabetology with the highest impact factor of 16.2. This abstract summarizes a comprehensive bibliometric analysis that provides insights into the global research field of LADA type, underscoring the importance of international collaboration and the significant contributions of leading countries and institutions in shaping our understanding of this complex subtype of diabetes.
Supplementary Data from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: October 2024

Overview of supplementary data
Figure S2 from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: October 2024

CBX2 expression associates with epithelial state 6. CBX2 protein expression does not correlate with T cell infiltration. CXCL1, 5, and CXCL8 expression correlation with Macrophage M0_CIBERSORT infiltration.
Impact of Concomitant Prescriptions and Lifestyle Factors on the Initial Course of Newly Diagnosed Inflammatory Bowel Disease
Authors: Morikubo Hiromu , Nagahama Takayoshi , Nagai Katsuhiko , Yamazaki Hajime , Kobayashi Taku
Published: October 2024

Introduction: There is a close relationship between the relapse of inflammatory bowel disease (IBD) and lifestyle factors, including concomitant medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), antithrombotic drugs, smoking status, and alcohol consumption. However, solid evidence is limited regarding the risk factors at diagnosis and initial disease course. This study aimed to explore the impact of concomitant prescriptions and lifestyle factors in patients with newly diagnosed IBD using a large-scale real-world database. Methods: This is a retrospective inception cohort study using the insurance claims database. Newly diagnosed patients with UC and CD were enrolled between January 2005 and May 2020. Concomitant prescriptions and lifestyle factors were assessed for new biologics use, surgery, and hospitalization during the first year. Results: In total, 6,743 patients with UC and 1,000 patients with CD were enrolled. Proton pump inhibitors, antithrombotics, antibiotics, and NSAIDs were identified as associated factors for both biologics use and hospitalization in UC patients (all p < 0.01), and antithrombotics were identified as associated factors for both biologics use and hospitalization in CD patients (all p < 0.01) in multivariable analyses. Interestingly, smoking was protective against hospitalization in UC patients (p < 0.01) but not in CD patients (p = 0.997), analyzed by univariate analysis. Alcohol consumption was protective against hospitalization outcomes in UC patients (p = 0.02) but not in CD patients (p = 0.27), analyzed by univariate analysis. Conclusion: Immediate attention should be paid to concomitant medications at diagnosis because they may have impact on the initial course of IBD.
Vizinhos
Authors: Francoy Daniel
Published: October 2024

Conto de Daniel Francoy.
Biological, social, and healthcare factors for death due to influenza A(H1N1) during the 2009 epidemic in Brazil
Authors: Braga Jose Ueleres , Ribeiro Ana Freitas
Published: October 2024

OBJECTIVE: To identify risk factors for death from inf luenza A(H1N1), including the effectiveness of the vaccine against influenza A(H1N1) concerning mortality. METHODS: A case-control of incident cases of inf luenza A(H1N1) reported in the epidemiological information systems of the states of São Paulo, Paraná, Pará, Amazonas, and Rio Grande do Sul was conducted. RESULTS: 305 participants were included, 70 of them cases and 235 controls, distributed as follows: Amazonas, 9 cases/10 controls; Pará, 22 cases/77 controls, São Paulo, 19 cases/49 controls; Paraná, 10 cases/54 controls; Rio Grande do Sul, 10 cases/45 controls. These participants had a mean age of 30 years, with 33 years among cases and 25 years among controls. There was a predominance of females both among the cases and controls. Biological (age), pre-existing diseases (congestive heart failure, respiratory disease, and diabetes mellitus), and care factors (ICU admission) associated with death from influenza A(H1N1) were identified. CONCLUSION: The risk factors identified in this investigation not only allowed subsidizing the elaboration of clinical conducts but also indicate important aspects for facing “new” influenza epidemics that are likely to occur in our country.
Abstract 10: Adrenal Zona Glomerulosa Long Form Leptin Receptor (LepRb) Protects from Leptin-Mediated Vascular Disorders in Female Mice
Authors: Ono Yoichi , Kennard Simone , Breault David , Belin De Chantemele Eric
Published: October 2024

Introduction:
Previous work from our group demonstrated that leptin is a major contributor to obesity-associated cardiovascular disease, in females, by acting on the adrenal gland to promote aldosterone production.

Hypothesis:
This leptin-mediated aldosterone secretion is dependent on the presence of the long form leptin receptor (LepRb) in adrenal aldosterone synthase (AS) expressing cells.

Methods:
We generated AS LepRb deficient mice, ASKO and WT control (ASWT), by crossing LepRb
flox/flox
mice with AS-Cre mice to investigate the role of LepRb in AS expressing cells in leptin-mediated cardiovascular alteration in females and also generated db/AS
+
mice that have LepRb only in AS expressing cells by crossing LepR
TBflox/flox
(db/db) with AS-Cre mice to compare their phenotype.

Results:
Under baseline conditions, ASKO female mice exhibited no alteration in adrenal AS, plasma aldosterone, systolic blood pressure, and aortic endothelium-dependent relaxation. To mimic obese conditions, we submitted ASWT and ASKO to chronic leptin infusion for a week. Leptin increased adrenal AS expression, aldosterone levels, and blood pressure and impaired endothelial function, which were further elevated in ASKO compared to ASWT, suggesting protective effects of AS LeRb. Both mineralocorticoid receptor (MR) antagonist. eplerenone, or AS antagonist, fadrazole, rescued endothelial function in ASWT and ASKO mice treated with leptin, indicating that leptin-mediated endothelial dysfunction is still aldosterone-dependent in ASKO mice. Restoration of LepRb in AS expressing cells in db/db decreased adrenal AS and plasma aldosterone and improved endothelial function further indicating that AS LepRb blunts leptin-mediated aldosterone production. On a molecular level, leptin treatment elevated aorta NOX1 expression in ASWT, which was further increased in ASKO. Aldosterone treatment increased NOX1 expression in cultured microvascular endothelial cells. Incubation of aortic rings with a selective NOX1 inhibitor restored endothelial function in both ASWT and ASKO treated with leptin, suggesting leptin-mediated aldosterone increased NOX1 expression in the aorta, which causes endothelial dysfunction.

Conclusion:
These data indicate that AS LepRb protects from leptin-mediated aldosterone production and vascular dysfunction by mitigating the effects of leptin on aldosterone production and suggests that other isoforms of LepR are involved in stimulating aldosterone production.
Abstract 16: A Novel H2 Relaxin B-Chain-Only Peptide Variant B7-33 Improves The Pathophysiology Of Placental Ischemia In The Reduced Uterine Perfusion Pressure Rat Model Of Preeclampsia
Authors: Pantho Ahmed F , Amaral Lorena , Campbell Nathan , Afroze Syeda , Vora Niraj , Kuehl Thomas , Lindheim Steven , Lamarca Babbette , Bathgate Ross , Hossain Mohammed , Uddin Mohammad
Published: October 2024

Background:
Preeclampsia (PE) is a hypertensive pregnancy disorder, which occurs in approximately 10% of all gestations. The literature suggests the potential therapeutic role of H2 relaxin in PE. A novel H2 relaxin B-chain-only peptide variant B7-33 (27 amino acids without any disulfide bonds) has recently been developed.

Objective:
The goal of this study was to test the hypothesis that a novel H2 relaxin B-chain-only peptide variant B7-33 could improve the pathophysiology of placental ischemia in the Reduced Uterine Perfusion Pressure (RUPP) rat model of PE.

Methods:
The efficacy of B7-33 was evaluated in the RUPP model as described previously. RUPP rats are randomly assigned to 4 groups (N=8/group): 1) vehicle, 2) B733; 3) B733-Fc; and 4) B733-HSA. Rats are dosed twice weekly (i.v.) from GD10 to GD 20. On GD 18, rats are anesthetized with isoflurane, and carotid arterial catheters are inserted into the carotid artery, tunneled under the skin, and externalized at the back of the neck. On the following day, mean arterial pressure (MAP) is monitored with a pressure transducer (Cobe III Tranducer CDX Sema) and recorded continuously for 30 min. On GD18, uterine artery resistance index (UARI) of rats is measured by Doppler sonography. The nitric oxide bioavailability, soluble fms-like tyrosine kinase-1 (sFlt-1), and TNF-α) were measured by commercially available kits. Statistical comparisons were performed using analysis of variance with Duncan’s post hoc test.

Results:
The RUPP rats have increased MAP (122.2 ± 8.1 mm Hg), plasma TNF-α (223 ±11.4 pg/mL), and plasma sFlt-1(863 ±18.2 pg/mL) along with decreased NO index (14±2 µM) compared to normal pregnancy: MAP (102 ± 5.2 mm Hg); plasma TNF-α (28 ± 4.1 pg/mL); plasma sFlt-1(244 ± 9.4 pg/mL) and NO index (26 ±4.1 µM). Treatment with B733 and B7-33 fusion proteins significantly (*p<0.05) lowers MAP, plasma TNF-α, and plasma sFlt-1 and increased NO index back to that of normal pregnancy. The B7-33 data are consistent with earlier data with serelaxin in the RUPP model. All fusions tested ameliorate hypertension in the RUPP animals. B7-33 normalizes BP and proteinuria in the DOCA rat model of preE.

Conclusion:
The conclusion of the study is that both B7-33 and B7-33 fusion proteins demonstrate efficacy in attenuating the symptoms of PE including hypertension and inflammation in RUPP model. We conclude that B7-33 is an ideal candidate for development as a novel therapeutic in preE.
Abstract 19: Effect of the endothelin receptor antagonist aprocitentan on plasma endothelin, renin and aldosterone concentrations in patients with resistant hypertension. A biomarker analysis of the PRECISION study.
Authors: Iglarz Marc , Blattmann Peter , Dreier Roland , Danaietash Parisa , Sassi-Sayadi Mouna , Clozel Martine
Published: October 2024

Hypothesis:
Dual endothelin (ET) ET
A
/ET
B
receptor antagonist aprocitentan significantly reduced blood pressure in patients with resistant hypertension, who were still hypertensive despite standard background anti-hypertensive drugs including a diuretic, an ARB and a CCB (PRECISION trial, NCT03541174). The effect of aprocitentan in this population, characterized with low renin and elevated aldosterone levels, was assessed on a panel of plasma biomarkers: ET-1, CT-proET-1 (a stable peptide and biomarker for ET-1 production), renin, aldosterone.

Methods:
From the 730 randomized patients in PRECISION, ET-1 (n=700), CT-proET-1 (n=100, randomly selected), immunoreactive renin (n=679) and aldosterone (n=703) were measured in plasma samples collected at randomization (baseline) and after 4 weeks for either placebo, aprocitentan 12.5 or 25 mg.

Results:
Four-week placebo treatment had no effect on the studied biomarkers compared to baseline. Treatment with aprocitentan 12.5 and 25 mg increased plasma ET-1 by +34% and +53% and CT-proET-1 by +38% and +47% vs. baseline respectively. Aprocitentan had no effect on renin levels (p>0.05) while decreasing plasma aldosterone by -17% and -24% at the 12.5 and 25 mg dose respectively. Importantly, the reduction in aldosterone did not result in a change in kalemia (see
Table
).

Conclusions:
Aprocitentan caused reactive dose-dependent increases in plasma CT-proET-1 and ET-1, resulting from effective ET receptor blockade. The increase in CT-proET-1 may indicate a compensatory increase in ET-1 de novo synthesis, while the increase in ET-1 may reflect a reduced clearance due to blockade of ET
B
and increased production. The decrease of aldosterone by aprocitentan confirms the secretagogue role of ET-1 on aldosterone production by adrenal cortical cells via both ET
A
and ET
B
receptors This decrease of aldosterone was observed on top of the known decrease induced by an ARB but did not induce hyperkalemia nor aggravation of renal function.
Abstract 21: The Detrimental Effects of a Comorbidity of Increased Blood Pressure Variability and High Salt Diet on Cardiovascular and Neurovascular Outcomes
Authors: Mendiola Perenkita , Xie Kun , Oherron Philip , Brands Michael , Patterson Rachel , Folk Cameron , Filosa Jessica
Published: October 2024

Recent studies have identified increased blood pressure variability (BPV) as a novel risk factor for cognitive decline, independently from absolute BP values. However, the underlying mechanisms are poorly defined. In addition, whether a high salt diet (HSD) contributes to BPV and exacerbates cognitive decline is not known. We tested the hypothesis that vascular damage resulting from blood pressure fluctuations in BPV disrupts critical mechanisms regulating cerebral blood flow (CBF), impairing perfusion and leading to neurovascular dysfunction and cognitive decline. We established a murine BPV model and evaluated the impact of BPV on systemic BP (baroreceptor reflex) and CBF regulation (myogenic and functional hyperemia (FH) responses). Mice were implanted with a cranial window for in-vivo two-photon (2P) imaging. A programmable pump infused 6-8 pulses/day of angiotensin II ((Ang II 18 µg/day) (BPV) or saline (Control) for 25 days, and cardiovascular variables were measured via DSI telemetry. Ang II pulse infusions evoked transient BP increases (Δ43±4 mmHg, MAP; P<0.01,n=8); however,
did not induce hypertension
in the BPV group. BPV mice displayed increased BPV index (P=0.04,n=12) and cognitive decline (novel object recognition test (P=0.01,n=10)). Telemetry data showed a decrease in bradycardic responses following chronic BPV (P=0.03, n=8). Data from 2P studies showed enhanced myogenic response in parenchymal arterioles of BPV vs Controls (P<0.01,n=9-15 runs) when BP transitions from low to high BP. We observed a blunted FH in BPV vs Control during low BP (P<0.01,n=6-7). During high BP, FH was pronounced in Controls (P<0.01,n=6-7); however, pressure-induced vascular responses were abolished in BPV mice (P<0.01,n=6-7). In separate groups of mice, the Control and BPV protocol was repeated with all mice receiving a high-salt diet (HS; 4% NaCl chow+1% NaCl drinking water: Control+HS or BPV+HS). There were no changes in 24-hr MAP in Control+HS (P>0.85, n=5). Whereas BPV+HS mice developed sustained hypertension (increased 24-hr MAP; P<0.01, n=4). These data demonstrate that BPV alters mechanisms regulating CBF and BP, contributing to cognitive decline and that HSD may exacerbate the detrimental effects of BPV on BP regulating mechanisms. Ongoing studies are examining the comorbid effects of BPV+HS on the cerebrovasculature and direct CBF changes in BPV and BPV+HS mice.
Abstract 22: Evaluation of the effects of CD8 knock-out on cognitive decline in the TAC-induced hypertension mouse model
Authors: Pacella Jacopo , Fardella Valentina , Migliaccio Agnese , Pallante Fabio , Carnevale Daniela , Lembo Giuseppe , Carnevale Lorenzo
Published: October 2024

Hypertension is one of the main risk factors for cognitive impairment and dementia. We and others demonstrated the role of immunoinflammatory challenges in the establishment of cerebral injury following hypertension, highlighting a major role of inflammatory cytokines as interferon-gamma (IFN-γ) and finding increased parenchymal infiltration of CD8+ T cells.

To establish the mechanistic role of these cells in cognitive impairment we subjected mice lacking CD8 cells (CD8 KO) and matched controls to aortic coarctation (TAC) and performed advanced neuroimaging analyses with a dedicated 7T small animal MRI, evaluating perfusion, brain volumes, and white matter microstructural integrity. Cognitive performance was evaluated at 4 weeks using the Morris Water Maze (MWM) test.

Brain perfusion analyses shown protection from cerebral hypoperfusion in TAC CD8 KO mice compared to TAC WT mice (TAC WT vs TAC KO: 108 vs 148 ml/100g/min, p=0.0298) (Figure A). CD8 KO show preserved microstructural structure at DTI MRI, a typical trait of cerebral injury in clinical and experimental hypertension (Fimbria Fractional Anisotropy, TAC WT vs TAC KO: 0.45 vs 0.54, p=0.0210) , and show no a preserved cognition at MWM (Figure B), with a preserved learning curve at acquisition trial and a preserved memory retention capability evidenced at the probe trial (TAC WT vs TAC KO: 16,4 vs 32.2 seconds spent in platform quadrant, p=0.0014).

The rescue from cerebral injury evidenced at MRI and the absence of cognitive impairment in CD8 KO mice demonstrate the pivotal role of CD8+ lymphocytes in the pathogenesis of hypertension-induced cognitive impairment.
Abstract 23: Cognitive impairment during chronic i.c.v. angiotensin II is associated with increased tau phosphorylation in the cortex and hippocampus
Authors: Zarate Sara , Santner Ava , Vissa Udaykiran , Santisteban Monica
Published: October 2024

Cardiovascular risk factors, such as hypertension, are recognized as important contributors to cognitive impairment and dementia, including Alzheimer’s disease (AD). However, the mechanisms underlying the detrimental effects of hypertension on the brain remain to be fully established. Angiotensin II (Ang II) has known detrimental effects on the brain, including cerebrovascular damage, sympathetic activation, and neuroinflammation. Ang II activates neuronal glycogen synthase 3b (GSK-3b), a major kinase involved in the phosphorylation of the microtubule associated protein tau. Hyperphosphorylated tau and the subsequent formation of neurofibrillary tangles are a hallmark of AD and related dementias (tauopathies). Here, we tested the central hypothesis that brain Ang II leads to cognitive impairment by increasing tau hyperphosphorylation. 3-month old male C57BL6 mice were implanted with a s.c. osmotic minipump connected to an i.c.v. cannula delivering low dose Ang II (6ng/hr) or saline for 4 weeks. Blood pressure was monitored twice weekly using tail-cuff plethysmography. During the 4
th
week of infusion, mice underwent a battery of neurobehavioral testing assessing various cognitive domains including novel object recognition (recognition and short-term memory), Y-maze (spatial working memory), Barnes maze (spatial learning and long-term memory), and hippocampal/executive function (nest building). Tau phosphorylation was assessed in the cortex and hippocampus by Western blotting. Systolic blood pressure increased slightly by week 3 prior to start of behavioral tests (control: 115.3 ± 4.1 mmHg vs Ang II: 130.8 ± 4.7; n=10). We did not observe significant differences during novel object recognition (discrimination index: control: 0.49 ± 0.08 vs Ang II: 0.35 ± 0.23; n=5) or Y-maze (spontaneous alternations: control: 62.4 ± 6.1% vs Ang II: 59.0 ± 4.3%). Mice receiving i.c.v. Ang II had significantly delayed latency to find the escape hole during the Barnes maze learning trials (Treatment p=0.0006, Time p=0.0039, interaction: p=0.3028; two-way repeated measures ANOVA). The impairment in spatial learning was associated with an increase in tau phosphorylation in the cortex assessed by AT8 antibody. Ongoing studies are investigating whether this increase is mediated by activation of neuronal GSK-3b. We conclude that Ang II-mediated hyperphosphorylation of tau is a potential novel molecular mechanism driving the detrimental effects of hypertension on cognitive health.