bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALISIS SENTIMEN BAHASA PADA ULASAN DALAM MEMPENGARUHI CITRA MERK PRODUK
Authors: Hamizar Arizal
Published: June 2024

AbstractThis study aims to analyze the sentiment of consumer reviews language towards the formation of brand image of a product in the context of online purchasing. This research focuses on how the language used in consumer reviews can influence perceptions of a product's brand image. A qualitative method is employed to gain in-depth insights into how consumers respond to existing product reviews. The sample consists of consumers who actively read other consumers' reviews before making a purchase. The results of the research show that sentiment language plays a role in shaping consumers' perceptions of a product's brand image. Positive sentiments in reviews tend to reinforce a positive brand image, while negative sentiments tend to damage it. The interpretation of sentiments is influenced by how much they align with consumers' preferences and their intensity. Strong sentiments have a more significant impact on brand image formation. Contextual factors and product characteristics also play a role in the influence of sentiment language on brand image. Products that are important to consumers have a greater impact of sentiment on brand perception.Keywords: Sentiment Language, brand image, reviews  AbstrakPenelitian ini bertujuan untuk menganalisis sentimen bahasa ulasan konsumen terhadap pembentukan citra merek produk dalam konteks pembelian online. Penelitian ini difokuskan pada bagaimana bahasa yang digunakan dalam ulasan konsumen dapat mempengaruhi persepsi terhadap citra merek suatu produk. Metode kualitatif digunakan untuk mendapatkan wawasan yang mendalam tentang bagaimana konsumen merespons ulasan produk yang ada. Sampel terdiri dari konsumen yang secara aktif membaca ulasan konsumen lain sebelum melakukan pembelian produk. Hasil penelitian menunjukkan bahasa sentimen memiliki peran dalam membentuk persepsi konsumen terhadap citra merek produk. Sentimen positif dalam ulasan cenderung memperkuat citra merekpositif, sementara sentimen negatif cenderung merusak citra merek. Interpretasi sentimen dipengaruhi oleh sejauh mana sentimen tersebut sejalan dengan preferensi konsumen dan intensitasnya. Sentimen yang sangat kuat memiliki dampak yang lebih signifikan pada pembentukan citra merek. Faktor kontekstual dan karakteristik produk juga memainkan peran dalam pengaruh bahasa sentimen pada citra merek. Produk yang penting bagi konsumen memiliki dampak sentimen yang lebih besar pada persepsi merek.Kata Kunci: Bahasa Sentimen, Citra Merek, Ulasan
Troponin: Think Before Testing
Authors: Ganiyu Shakirat , Bello Fatimah , Stone Danielle , Ruhnke Gregory , Stone James
Published: June 2024

This is a high-value care-based quality improvement project that was carried out to decrease inappropriate troponin testing in the emergency department (ED) of a tertiary health institution in the United States with the goal of promoting evidence-based practices, minimizing waste, and enhancing the quality of care.
Киберэтничность чувашей: репрезентационные практики / Cyber-Ethnicity of the Chuvash: Representational Practices
Authors: Ягафова Е.А.
Published: June 2024

В статье рассмотрена структура чувашского киберпространства, дана характеристика этнического (чувашского) контента, представлены формы и способы репрезентации этничности, оценена роль интернет-пространства в формировании и поддержании этнической идентичности чувашей. Исследование показало, что виртуальное пространство этничности чувашей является проекцией реального, отражает самосознание народа и его региональных сообществ, содержит актуальные формы и способы выражения идентичности в публичной среде через этнически маркированные элементы культуры, с помощью которых конструируется этнический образ, влияющий на формирование и сохранение этничности чувашей в реальном мире. Киберпространство чувашей служит одним из эффективных способов и средств удовлетворения этнических потребностей в ограниченных условиях реального общения и приобщения к культурно-языковым ценностям своего народа, способствует трансляции знаний об истории традиционной культуре народа, внутриэтнической коммуникации, обмену информации пользователей сетей и их интеграции в виртуальное пространство.
The article examines the structure of the Chuvash cyberspace, characterizes the ethnic (Chuvash) content, describes the forms and methods of representing ethnicity, and evaluates the role of the Internet in the shaping and maintaning the Chuvash ethnic identity. The virtual space of Chuvash ethnicity is a projection of the real one, it reflects the self-awareness of the people and their regional communities, contains current forms and ways of expressing identity in the public environment through ethnically marked cultural elements, which help to construct an ethnic image that influences the formation and preservation of Chuvash ethnicity in the real world. The cyberspace of the Chuvash is an effective way of satisfying ethnic needs and familiarization with the cultural and linguistic values of their people when real communication is limited, promotes the transmission of knowledge about the history of the traditional culture of the people, intra-ethnic communication, the exchange of information among network users and their integration into the virtual space.
Анархия-в-деревне: переосмысление «сельского» как нового либертарного устройства общества / “In-Village Anarchy”: Rethinking “Rural” as a New Libertarian Way of Social Living
Authors: Крыков Е.А.
Published: June 2024

Идеи либертарной идеологии «зеленого» анархизма, в основе которой лежит радикальная критика городского индустриального производства и связанной с ним переориентации системы ценностей человека в капиталистическом обществе, находят свое выражение в создании экологических поселений, организованных по принципам неирархического и экологического сознания автономных хуторов как сетевых единиц и разработки горизонтальных социальных связей. В статье предлагается к рассмотрению анархистское переосмысление «сельского» в контексте практик освоения не-городского пространства с целью построить новое общество. Автор анализирует сквоттинг как специфический метод и философию в контексте опыта мировых проектов городских и сельских анархических объединений, включая мировые проекты идейных общин и соотнося его с ситуацией в России. На основе выводов о собранной информации от активистов по российской сквот-коммуне Сквошино анализируются особенности быта современных строителей анархии-в-деревне и рассматривается «новизна» иной формы устройства общества как декларируемой альтернативы провальной анархии-в-городе и городскому образу жизни в целом.
The ideas of the “green” anarchism libertarian ideology, based on a radical criticism of urban industrial production and the associated reorientation of the human value system in a capitalist society, find their expression in ecological settlements, organized according to the principles of non-hierarchical and ecological consciousness of autonomous homesteads as network units and development of horizontal social connections. This article proposes to consider the anarchist rethinking of the “rural” in the context of the practices of developing non-urban space in order to build a new society. The author analyzes squatting as a specific method and philosophy in the context of the experience of global projects of rural and urban anarchist communities, including global projects of ideological communes and comparing this experience with the situation in Russia. The paper analyzes the collected information from activists in the Russian squat commune Skvoshino and provides reflection on the life of modern builders of “in-village anarchy” and the “novelty” of a different form of social structure as a declared alternative to the “failed in-city anarchy” and the urban way of life in general.
Modeling and validation of drug release kinetics using hybrid method for prediction of drug efficiency and novel formulations
Authors: Alshahrani Saad M. , Alotaibi Hadil Faris , Alqarni Mohammed
Published: June 2024

This paper presents a thorough examination for drug release from a polymeric matrix to improve understanding of drug release behavior for tissue regeneration. A comprehensive model was developed utilizing mass transfer and machine learning (ML). In the machine learning section, three distinct regression models, namely, Decision Tree Regression (DTR), Passive Aggressive Regression (PAR), and Quadratic Polynomial Regression (QPR) applied to a comprehensive dataset of drug release. The dataset includes r(m) and z(m) inputs, with corresponding concentration of solute in the matrix (C) as response. The primary objective is to assess and compare the predictive performance of these models in finding the correlation between input parameters and chemical concentrations. The hyper-parameter optimization process is executed using Sequential Model-Based Optimization (SMBO), ensuring the robustness of the models in handling the complexity of the controlled drug release. The Decision Tree Regression model exhibits outstanding predictive accuracy, with an R2 score of 0.99887, RMSE of 9.0092E-06, MAE of 3.51486E-06, and a Max Error of 6.87000E-05. This exceptional performance underscores the model’s capability to discern intricate patterns within the drug release dataset. The Passive Aggressive Regression model, while displaying a slightly lower R2 score of 0.94652, demonstrates commendable predictive capabilities with an RMSE of 6.0438E-05, MAE of 4.82782E-05, and a Max Error of 2.36600E-04. The model’s effectiveness in capturing non-linear relationships within the dataset is evident. The Quadratic Polynomial Regression model, designed to accommodate quadratic relationships, yields a noteworthy R2 score of 0.95382, along with an RMSE of 5.6655E-05, MAE of 4.49198E-05, and a Max Error of 1.86375E-04. These results affirm the model’s proficiency in capturing the inherent complexities of the drug release system.
Rothia dentocariosa endocarditis with brain abscess and splenic abscess: case report and brief review
Authors: Zheng Xue , Liu Fang , Ma Qiaoli , Li Jing , Ma Huiping
Published: June 2024

Rothia dentocariosa is a conditionally pathogenic bacterium that may cause infective endocarditis (IE) in selected patients and give rise to a variety of clinical complications, albeit it is not a common IE pathogen. We present the case of a patient diagnosed with Rothia dentocariosa-associated IE secondary to influenza B and thrombocytopenic purpura. The blood culture revealed Rochebacterium caries, cardiac ultrasound detected vegetation, while brain and spleen abscesses manifested and progressively deteriorated. Despite a suboptimal response to anti-infective therapy, the patient ultimately underwent aortic valve replacement. Discharge from the hospital was achieved upon control of the brain abscess and spleen abscess.
Seismically-induced permanent displacements of slopes using 3D Nested Newmark method
Authors: Li Qiang , Tong Yan-Yang , Wang Jin-Nan , Xu Hui
Published: June 2024

The Newmark method is a classic method for evaluating the permanent displacements of a slope under seismic loads. This study aims at proposing a three-dimensional nested Newmark method (3D-NNM) in the framework of the kinematic theorem of limit analysis. The classical three-dimensional rotational failure mechanism is discretized into a series of nested rotating wedges, each of which is subjected to a corresponding yield acceleration determined by employing the work rate balance, and each of which produces relative displacements under seismic excitations when it exceeds the yield acceleration. The total permanent displacement profile is further obtained by integration of the relative displacements from the slope toe to the slope crest. The obtained results show that the proposed 3D-NNM can effectively evaluate the permanent displacement profile of slopes under earthquakes, and the proposed 3D-NNM improves the Leshchinsky’s 2D nested Newmark method by 30.7%; the obtained total horizontal displacement at the slope middle height reduces with the number of nested blocks, but increases with the increasing of the slope-width-to-height ratios. Besides, the traditional Newmark method with a single sliding block tends to overestimate the permanent displacements of slope under seismic shakings.
Model of motivational competence: creation of students’ motivation, assessment, and research
Authors: Satka Fjoralba , Garneva Emilia
Published: June 2024

The basic finding uniting the researchers is that motivation is the weakest educational component, which prompted us to create and suggest a practical model of motivational competence. The project is based on the researchers’ descriptions of students’ motivational leading variables. Our main finding is lack of a value system and moral virtues in the foundation of motivation. The constructive components of the model cognition, cogitation, and skills were built on that basis. The main functional approaches in the study with the model are communication, feedback, and critical thinking. The model aims: (1) to direct teachers in creating and maintaining students’ motivation through motivational competence based on human values and virtues and (2) to strongly recommend that educational policies must pinpoint a value system and moral criteria for schools and universities so that educators can rigorously develop them in students through motivation. The contributions of the model are: (1) it is based on the crucial need for a strong value system and moral virtues in the foundation of students’ motivation and behavior; (2) it is bidirectional—developing students’ motivational competence, in parallel it increases teachers’ motivational competencies; (3) it argues that motivational competence must be the professional imperative leading to the curriculum purposes of teaching–learning process on the foundation of competence, high spiritual qualities, and morality.
Updates in the skeletal and joint protective effects of tocotrienol: a mini review
Authors: Chin Kok-Yong
Published: June 2024

Osteoporosis and osteoarthritis continue to pose significant challenges to the aging population, with limited preventive options and pharmacological treatments often accompanied by side effects. Amidst ongoing efforts to discover new therapeutic agents, tocotrienols (TTs) have emerged as potential candidates. Derived from annatto bean and palm oil, TTs have demonstrated efficacy in improving skeletal and joint health in numerous animal models of bone loss and osteoarthritis. Mechanistic studies suggest that TTs exert their effects through antioxidant, anti-inflammatory, Wnt-suppressive, and mevalonate-modulating mechanisms in bone, as well as through self-repair mechanisms in chondrocytes. However, human clinical trials in this field remain scarce. In conclusion, TTs hold promise as agents for preventing osteoporosis and osteoarthritis, pending further evidence from human clinical trials.
Study on the optimum value of remanent magnetism for suppressing ferromagnetic resonance of voltage transformer in all-cable line
Authors: Yonghao Huang , Shuheng Dan , Zhiyuan Liu
Published: June 2024

Introduction: Due to the need for safety and aesthetics, 10 kV urban power grids are gradually dominated by all-cable lines. However, this trend also brings new challenges. Cables, which are equivalent to capacitors at industrial frequency, are prone to resonate with the voltage transformers (PTs) in the system, causing drastic changes in current and voltage and posing a threat to the stable operation of the system. In addition, the intrusion of lightning waves into the substation will lead to different residual magnetization in the PT core, which further changes the core inductance value and affects the ferromagnetic resonance of the system to a certain extent.

Methods: In order to deeply investigate the influence of remanent magnetism on the ferromagnetic resonance of the system, this paper establishes a simulation model of a 10 kV all-cable line based on the PSCAD software, and adopts a UMEC transformer capable of simulating the saturation characteristics to construct the PT, and simulates the intrusion currents by using a DC current source in order to generate remanent magnetism. By this method, the effect of remanent magnetization on the ferromagnetic resonance of the system is explored at different magnitudes and directions.

Results: The results of the study show that the residual magnetization has a significant effect on the ferromagnetic resonant inrush current of the voltage transformer. When the remanent magnetization value is positive and less than 0.6 pu, the ferromagnetic resonance inrush current of PT can be effectively suppressed, and the smaller the remanent magnetization value is, the better the suppression effect is. However, negative remanent magnetization cannot suppress the ferromagnetic resonance of the PT, but may exacerbate the inrush current, leading to more serious consequences.

Conclusion: This study helps to improve the stability of the power grid and also provides a valuable reference for future grid design and maintenance.
Burn pit exposure in military personnel and the potential resulting lung and neurological pathologies
Authors: Penuelas Veronica L. , Lo David D.
Published: June 2024

Introduction

Military personnel and local civilians at various deployment locations are plagued with serious health conditions. Evidence points to burn pit emissions as the cause of these pathologies; however, similar diseases are also caused by environmental exposures, smoking, genetic predispositions, or other comorbidities. Burn pits, which are large smoldering piles of refuse ignited with jet or diesel fuel, contain human and medical waste as well as paint, plastics, ammunition, and other materials—each of which can be attributed to health concerns in other industrial settings. Here we compare various pathologies attributable to toxic aerosol exposures and discuss distinct pathologies that may be linked to burn pit exposures.

Objectives

We performed a literature review where we provide information on toxic exposures that may pose relevance to burn pit exposure and furthermore, highlight what is already known about burn pit exposures and what steps need to be taken to diagnose and correlate certain respiratory pathologies to chronic exposure from overseas burn pits.

Data sources

We conducted searches through PubMed and Google Scholar to determine where gaps in our knowledge of burn pit exposure lie. Thorough review on jet-fuel properties and particulate matter were performed as supporting evidence of potential toxins from burn pit emissions.

Results

To date, studies on burn pit emissions consist mainly of systematic reviews and discussions to address the problem, with very few acute-exposure studies and little to no chronic-exposure studies. We found that symptoms range from respiratory pathologies to neurological deficits, but treatment has been limited as medical facilities, such as the Veterans Administration (VA), require proof that a condition is service-connected.

Conclusions

To determine the effects of burn pit exposure on humans, chronic exposure to mimicked burn pit emissions is necessary to draw definitive conclusions between phenotypic differences in pathologies linked to exposure. By determining phenotypic differences, conclusions can be made about the pathologic origins, potentially leading to future diagnoses and treatments for veterans and affected civilians.
The disutility of compartmental model forecasts during the COVID-19 pandemic
Authors: Sudhakar Tarini , Bhansali Ashna , Walkington John , Puelz David
Published: June 2024

During the COVID-19 pandemic, several forecasting models were released to predict the spread of the virus along variables vital for public health policymaking. Of these, the susceptible–infected–recovered (SIR) compartmental model was the most common. In this paper, we investigated the forecasting performance of The University of Texas COVID-19 Modeling Consortium SIR model. We considered the following daily outcomes: hospitalizations, ICU patients, and deaths. We evaluated the overall forecasting performance, highlighted some stark forecast biases, and considered forecast errors conditional on different pandemic regimes. We found that this model tends to overforecast over the longer horizons and when there is a surge in viral spread. We bolstered these findings by linking them to faults with the SIR framework itself.
IgG4-related disease with nasopharyngeal malignancy-like manifestations
Authors: Lin Xijun , Lin Peiliang , Fan Jianming , Zhang Biying , Liang Faya , Han Ping , Liu Xiang , Huang Xiaoming
Published: June 2024

Background

IgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD.

Case summary

Four patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD.

Conclusion

The described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases.
Phenolic acids from medicinal and edible homologous plants: a potential anti-inflammatory agent for inflammatory diseases
Authors: Xie Jingchen , Xiong Suhui , Li Yamei , Xia Bohou , Li Minjie , Zhang Zhimin , Shi Zhe , Peng Qiuxian , Li Chun , Lin Limei , Liao Duanfang
Published: June 2024

Inflammation has been shown to trigger a wide range of chronic diseases, particularly inflammatory diseases. As a result, the focus of research has been on anti-inflammatory drugs and foods. In recent years, the field of medicinal and edible homology (MEH) has developed rapidly in both medical and food sciences, with 95% of MEH being associated with plants. Phenolic acids are a crucial group of natural bioactive substances found in medicinal and edible homologous plants (MEHPs). Their anti-inflammatory activity is significant as they play a vital role in treating several inflammatory diseases. These compounds possess enormous potential for developing anti-inflammatory drugs and functional foods. However, their development is far from satisfactory due to their diverse structure and intricate anti-inflammatory mechanisms. In this review, we summarize the various types, structures, and distribution of MEHP phenolic acids that have been identified as of 2023. We also analyze their anti-inflammatory activity and molecular mechanisms in inflammatory diseases through NF-κB, MAPK, NLRP3, Nrf2, TLRs, and IL-17 pathways. Additionally, we investigate their impact on regulating the composition of the gut microbiota and immune responses. This analysis lays the groundwork for further exploration of the anti-inflammatory structure-activity relationship of MEHP phenolic acids, aiming to inspire structural optimization and deepen our understanding of their mechanism, and provides valuable insights for future research and development in this field.
The biological function of Serpinb9 and Serpinb9-based therapy
Authors: Huang Haozhe , Mu Yiqing , Li Song
Published: June 2024

Recent breakthroughs in discovering novel immune signaling pathways have revolutionized different disease treatments. SERPINB9 (Sb9), also known as Proteinase Inhibitor 9 (PI-9), is a well-known endogenous inhibitor of Granzyme B (GzmB). GzmB is a potent cytotoxic molecule secreted by cytotoxic T lymphocytes and natural killer cells, which plays a crucial role in inducing apoptosis in target cells during immune responses. Sb9 acts as a protective mechanism against the potentially harmful effects of GzmB within the cells of the immune system itself. On the other hand, overexpression of Sb9 is an important mechanism of immune evasion in diseases like cancers and viral infections. The intricate functions of Sb9 in different cell types represent a fine-tuned regulatory mechanism for preventing immunopathology, protection against autoimmune diseases, and the regulation of cell death, all of which are essential for maintaining health and responding effectively to disease challenges. Dysregulation of the Sb9 will disrupt human normal physiological condition, potentially leading to a range of diseases, including cancers, inflammatory conditions, viral infections or other pathological disorders. Deepening our understanding of the role of Sb9 will aid in the discovery of innovative and effective treatments for various medical conditions. Therefore, the objective of this review is to consolidate current knowledge regarding the biological role of Sb9. It aims to offer insights into its discovery, structure, functions, distribution, its association with various diseases, and the potential of nanoparticle-based therapies targeting Sb9.
Multidisciplinary approaches to combat emerging viruses: diagnostics, therapeutic gene and vaccine delivery, and nanotherapeutics
Authors: Yu Xianqiang , He Qing , Kong Qingming
Published: June 2024

Emerging viruses, such as filoviruses (Ebola, Marburg), SARS and MERS coronaviruses, and Zika, pose significant threats to global public health, particularly for individuals with co-morbidities. To address these challenges, this review article explores multidisciplinary strategies for combatting emerging viruses. We emphasize the importance of developing accurate diagnostics, innovative therapeutic gene and vaccine delivery systems, and long-acting nanotherapeutics. These approaches are designed to enhance the safety and efficacy of treatments against these deadly pathogens. We discuss the collaborative efforts of virologists, geneticists, formulation scientists, clinicians, immunologists, and medicinal chemists in advancing these therapeutic modalities.
Fermented Aronia melanocarpa pomace improves the nutritive value of eggs, enhances ovarian function, and reshapes microbiota abundance in aged laying hens
Authors: Li Zhihua , Qin Binghua , Chen Ting , Kong Xiangfeng , Zhu Qian , Azad Md. Abul Kalam , Cui Yadong , Lan Wei , He Qinghua
Published: June 2024

Introduction

There is a decline in the quality and nutritive value of eggs in aged laying hens. Fruit pomaces with high nutritional and functional values have gained interest in poultry production to improve the performance.

Methods

The performance, egg nutritive value, lipid metabolism, ovarian health, and cecal microbiota abundance were evaluated in aged laying hens (320 laying hens, 345-day-old) fed on a basal diet (control), and a basal diet inclusion of 0.25%, 0.5%, or 1.0% fermented Aronia melanocarpa pomace (FAMP) for eight weeks.

Results

The results show that 0.5% FAMP reduced the saturated fatty acids (such as C16:0) and improved the healthy lipid indices in egg yolks by decreasing the atherogenicity index, thrombogenic index, and hypocholesterolemia/hypercholesterolemia ratio and increasing health promotion index and desirable fatty acids (P < 0.05). Additionally, FAMP supplementation (0.25%−1.0%) increased (P < 0.05) the ovarian follicle-stimulating hormone, luteinizing hormone, and estrogen 2 levels, while 1.0% FAMP upregulated the HSD3B1 expression. The expression of VTG II and ApoVLDL II in the 0.25% and 0.5% FAMP groups, APOB in the 0.5% FAMP group, and ESR2 in the 1% FAMP group were upregulated (P < 0.05) in the liver. The ovarian total antioxidant capacity was increased (P < 0.05) by supplementation with 0.25%−1.0% FAMP. Dietary 0.5% and 1.0% FAMP downregulated (P < 0.05) the Keap1 expression, while 1.0% FAMP upregulated (P < 0.05) the Nrf2 expression in the ovary. Furthermore, 1.0% FAMP increased cecal acetate, butyrate, and valerate concentrations and Firmicutes while decreasing Proteobacteria (P < 0.05).

Conclusion

Overall, FAMP improved the nutritive value of eggs in aged laying hens by improving the liver–blood–ovary function and cecal microbial and metabolite composition, which might help to enhance economic benefits.
Changes in hippocampal volume, synaptic plasticity and amylin sensitivity in an animal model of type 2 diabetes are associated with increased vulnerability to amyloid-beta in advancing age
Authors: Tarhan Melih , Hartl Tim , Shchyglo Olena , Colitti-Klausnitzer Jens , Kuhla Angela , Breuer Tobias Maximilian , Manahan-Vaughan Denise
Published: June 2024

Type-2 diabetes (T2D) is a metabolic disorder that is considered a risk factor for Alzheimer's disease (AD). Cognitive impairment can arise due to hypoglycemia associated with T2D, and hyperamylinemia associated with insulin resistance can enhance AD pathology. We explored whether changes occur in the hippocampus in aging (6–12 months old) female V-Lep○b-/- transgenic (tg) mice, comprising an animal model of T2D. We also investigated whether an increase in vulnerability to Aβ (1–42), a known pathological hallmark of AD, is evident. Using magnetic resonance imaging we detected significant decreases in hippocampal brain volume in female tg-mice compared to wild-type (wt) littermates. Long-term potentiation (LTP) was impaired in tg compared to wt mice. Treatment of the hippocampus with Aβ (1–42) elicited a stronger debilitation of LTP in tg compared to wt mice. Treatment with an amylin antagonist (AC187) significantly enhanced LTP in wt and tg mice, and rescued LTP in Aβ (1–42)-treated tg mice. Taken together our data indicate that a T2D-like state results in an increased vulnerability of the hippocampus to the debilitating effects of Aβ (1–42) and that effects are mediated in part by changes in amylin receptor signaling.
NoC simulation steered by NEST: McAERsim and a Noxim patch
Authors: Robens Markus , Kleijnen Robert , Schiek Michael , van Waasen Stefan
Published: June 2024

Introduction

Great knowledge was gained about the computational substrate of the brain, but the way in which components and entities interact to perform information processing still remains a secret. Complex and large-scale network models have been developed to unveil processes at the ensemble level taking place over a large range of timescales. They challenge any kind of simulation platform, so that efficient implementations need to be developed that gain from focusing on a set of relevant models. With increasing network sizes imposed by these models, low latency inter-node communication becomes a critical aspect. This situation is even accentuated, if slow processes like learning should be covered, that require faster than real-time simulation.

Methods

Therefore, this article presents two simulation frameworks, in which network-on-chip simulators are interfaced with the neuroscientific development environment NEST. This combination yields network traffic that is directly defined by the relevant neural network models and used to steer the network-on-chip simulations. As one of the outcomes, instructive statistics on network latencies are obtained. Since time stamps of different granularity are used by the simulators, a conversion is required that can be exploited to emulate an intended acceleration factor.

Results

By application of the frameworks to scaled versions of the cortical microcircuit model—selected because of its unique properties as well as challenging demands—performance curves, latency, and traffic distributions could be determined.

Discussion

The distinct characteristic of the second framework is its tree-based source-address driven multicast support, which, in connection with the torus topology, always led to the best results. Although currently biased by some inherent assumptions of the network-on-chip simulators, the results suit well to those of previous work dealing with node internals and suggesting accelerated simulations to be in reach.
Composing recurrent spiking neural networks using locally-recurrent motifs and risk-mitigating architectural optimization
Authors: Zhang Wenrui , Geng Hejia , Li Peng
Published: June 2024

In neural circuits, recurrent connectivity plays a crucial role in network function and stability. However, existing recurrent spiking neural networks (RSNNs) are often constructed by random connections without optimization. While RSNNs can produce rich dynamics that are critical for memory formation and learning, systemic architectural optimization of RSNNs is still an open challenge. We aim to enable systematic design of large RSNNs via a new scalable RSNN architecture and automated architectural optimization. We compose RSNNs based on a layer architecture called Sparsely-Connected Recurrent Motif Layer (SC-ML) that consists of multiple small recurrent motifs wired together by sparse lateral connections. The small size of the motifs and sparse inter-motif connectivity leads to an RSNN architecture scalable to large network sizes. We further propose a method called Hybrid Risk-Mitigating Architectural Search (HRMAS) to systematically optimize the topology of the proposed recurrent motifs and SC-ML layer architecture. HRMAS is an alternating two-step optimization process by which we mitigate the risk of network instability and performance degradation caused by architectural change by introducing a novel biologically-inspired “self-repairing” mechanism through intrinsic plasticity. The intrinsic plasticity is introduced to the second step of each HRMAS iteration and acts as unsupervised fast self-adaptation to structural and synaptic weight modifications introduced by the first step during the RSNN architectural “evolution.” We demonstrate that the proposed automatic architecture optimization leads to significant performance gains over existing manually designed RSNNs: we achieve 96.44% on TI46-Alpha, 94.66% on N-TIDIGITS, 90.28% on DVS-Gesture, and 98.72% on N-MNIST. To the best of the authors' knowledge, this is the first work to perform systematic architecture optimization on RSNNs.
Renshen Yangrong decoction for secondary malaise and fatigue: network pharmacology and Mendelian randomization study
Authors: Wang Fanghan , Zhu Liping , Cui Haiyan , Guo Shanchun , Wu Jingliang , Li Aixiang , Wang Zhiqiang
Published: June 2024

Background

Renshen Yangrong decoction (RSYRD) has been shown therapeutic effects on secondary malaise and fatigue (SMF). However, to date, its bioactive ingredients and potential targets remain unclear.

Purpose

The purpose of this study is to assess the potential ingredients and targets of RSYRD on SMF through a comprehensive strategy integrating network pharmacology, Mendelian randomization as well as molecular docking verification.

Methods

Search for potential active ingredients and corresponding protein targets of RSYRD on TCMSP and BATMAN-TCM for network pharmacology analysis. Mendelian randomization (MR) was performed to find therapeutic targets for SMF. The eQTLGen Consortium (sample sizes: 31,684) provided data on cis-expression quantitative trait loci (cis-eQTL, exposure). The summary data on SMF (outcome) from genome-wide association studies (GWAS) were gathered from the MRC-IEU Consortium (sample sizes: 463,010). We built a target interaction network between the probable active ingredient targets of RSYRD and the therapeutic targets of SMF. We next used drug prediction and molecular docking to confirm the therapeutic value of the therapeutic targets.

Results

In RSYRD, network pharmacology investigations revealed 193 possible active compounds and 234 associated protein targets. The genetically predicted amounts of 176 proteins were related to SMF risk in the MR analysis. Thirty-seven overlapping targets for RSYRD in treating SMF, among which six (NOS3, GAA, IMPA1, P4HTM, RB1, and SLC16A1) were prioritized with the most convincing evidence. Finally, the 14 active ingredients of RSYRD were identified as potential drug molecules. The strong affinity between active components and putative protein targets was established by molecular docking.

Conclusion

This study revealed several active components and possible RSYRD protein targets for the therapy of SMF and provided novel insights into the feasibility of using Mendelian randomization for causal inference between Chinese medical formula and disease.
Thrombocytopenia and hyperprogression after radiotherapy and camrelizumab treatment in an esophageal cancer patient with increased JAK2 gene copies: a case report
Authors: Wang Hang , Li Yun , Qiu Min , Wang Jianmin
Published: June 2024

Radiotherapy (RT) and immune checkpoint inhibitor (ICI) are important treatments for esophageal cancer. Some studies have confirmed the safety and effectiveness of using RT in combination with ICI, while serious side effects have been exhibited by some patients. We report a patient with metastatic esophageal cancer who received RT combined with ICI. The patient experienced severe thrombocytopenia, and treatment with thrombopoietin and corticosteroids were ineffective. Finally, the patient developed abscopal hyperprogression outside the radiation field. Interestingly, next-generation sequencing revealed increased JAK2 gene copies in the surgical slices. The JAK2/STAT3 pathway is involved in the regulation of megakaryocyte development. Recurrent thrombocytopenia may activate the JAK2/STAT3 pathway, leading to megakaryocyte differentiation and platelet biogenesis. However, persistent activation of the JAK2/STAT3 pathway has been associated with immune ICI resistance and tumor progression. This case indicates that thrombocytopenia and increased JAK2 gene copies may be risk factors for poor prognosis after ICI and RT treatment.
A pharmacovigilance study of chronic kidney disease in diabetes mellitus patients with statin treatment by using the US Food and Drug Administration adverse event reporting system
Authors: Zhang Jingyi , Guo Yuting , Wei Chunyan , Yan Yu , Shan Huifang , Wu Bin , Wu Fengbo
Published: June 2024

Background

Statins were regarded as a main medication for managing hypercholesterolemia. Administration of statin therapy could reduce the incidence of cardiovascular disease in individuals diagnosed with type 2 diabetes mellitus (DM), which was recognized by multipal clinical guidelines. But previous studies had conflicting results on whether the long-term use of statins could benefit the renal function in diabetic patients.

Aim

To evaluate the association between statin treatment and Chronic Kidney Disease in DM patients.

Methods

This is a retrospective disproportionality analysis and cohort study based on real-world data. All DM cases reported in US Food and Drug Administration adverse event reporting system (FAERS) between the first quarter of 2004 and the fourth quarter of 2022 were included. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). We further compared the CKD odds ratio (OR) between the statins group and the other primary suspected drug group among the included diabetes mellitus cases.

Results

We finally included 593647 DM cases from FAERS, 5113 (5.31%) CKD cases in the statins group and 8810 (1.77%) CKD cases in the control group. Data analysis showed that the statins group showed a significant CKD signal (ROR: 3.11, 95% CI: 3.00–3.22; IC: 1.18, 95% CI: 1.07–1.29). In case group with two or more statins treatment history, the CKD signal was even stronger (ROR: 19.56, 95% CI: 18.10–21.13; IC: 3.70, 95% CI:3.44–3.93) compared with cases with one statin treatment history.

Conclusion

The impact of statin therapy on the progression of renal disease in individuals diagnosed with type 2 diabetes mellitus (DM) remains inconclusive. After data mining on the current FAERS dataset, we discovered significant signals between statin treatment and CKD in diabetic patients. Furthermore, the incidence rate of CKD was higher among DM patients who used statins compared to those who did not.
Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress
Authors: Barinda Agian Jeffilano , Hardi Harri , Louisa Melva , Khatimah Nurul Gusti , Marliau Rheza Meida , Felix Immanuel , Fadhillah Muhamad Rizqy , Jamal Arief Kurniawan
Published: June 2024

With the increase in life expectancy, aging has emerged as a significant health concern. Due to its various mechanisms of action, cardiometabolic drugs are often repurposed for other indications, including aging. This systematic review analyzed and highlighted the repositioning potential of cardiometabolic drugs to increase lifespan as an aging parameter in animal studies and supplemented by information from current clinical trial registries. Systematic searching in animal studies was performed based on PICO: “animal,” “cardiometabolic drug,” and “lifespan.” All clinical trial registries were also searched from the WHO International Clinical Trial Registry Platform (ICTRP). Analysis of 49 animal trials and 10 clinical trial registries show that various cardiovascular and metabolic drugs have the potential to target lifespan. Metformin, acarbose, and aspirin are the three most studied drugs in animal trials. Aspirin and acarbose are the promising ones, whereas metformin exhibits various results. In clinical trial registries, metformin, omega-3 fatty acid, acarbose, and atorvastatin are currently cardiometabolic drugs that are repurposed to target aging. Published clinical trial results show great potential for omega-3 and metformin in healthspan.

Systematic Review Registration:crd.york.ac.uk/prospero/display_record.php?RecordID=457358, identifier: CRD42023457358.
CaMKIIδ-dependent dysregulation of atrial Na+ homeostasis promotes pro-arrhythmic activity in an obstructive sleep apnea mouse model
Authors: Hegner Philipp , Ofner Florian , Schaner Benedikt , Gugg Mathias , Trum Maximilian , Lauerer Anna-Maria , Maier Lars Siegfried , Arzt Michael , Lebek Simon , Wagner Stefan
Published: June 2024

Background

Obstructive sleep apnea (OSA) has been linked to various pathologies, including arrhythmias such as atrial fibrillation. Specific treatment options for OSA are mainly limited to symptomatic approaches. We previously showed that increased production of reactive oxygen species (ROS) stimulates late sodium current through the voltage-dependent Na+ channels via Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ), thereby increasing the propensity for arrhythmias. However, the impact on atrial intracellular Na+ homeostasis has never been demonstrated. Moreover, the patients often exhibit a broad range of comorbidities, making it difficult to ascertain the effects of OSA alone.

Objective

We analyzed the effects of OSA on ROS production, cytosolic Na+ level, and rate of spontaneous arrhythmia in atrial cardiomyocytes isolated from an OSA mouse model free from comorbidities.

Methods

OSA was induced in C57BL/6 wild-type and CaMKIIδ-knockout mice by polytetrafluorethylene (PTFE) injection into the tongue. After 8 weeks, their atrial cardiomyocytes were analyzed for cytosolic and mitochondrial ROS production via laser-scanning confocal microscopy. Quantifications of the cytosolic Na+ concentration and arrhythmia were performed by epifluorescence microscopy.

Results

PTFE treatment resulted in increased cytosolic and mitochondrial ROS production. Importantly, the cytosolic Na+ concentration was dramatically increased at various stimulation frequencies in the PTFE-treated mice, while the CaMKIIδ-knockout mice were protected. Accordingly, the rate of spontaneous Ca2+ release events increased in the wild-type PTFE mice while being impeded in the CaMKIIδ-knockout mice.

Conclusion

Atrial Na+ concentration and propensity for spontaneous Ca2+ release events were higher in an OSA mouse model in a CaMKIIδ-dependent manner, which could have therapeutic implications.
Polymyxins: recent advances and challenges
Authors: Yang Shan , Wang Hairui , Zhao Dan , Zhang Shurong , Hu Chenggong
Published: June 2024

Antibiotic resistance is a pressing global health challenge, and polymyxins have emerged as the last line of defense against multidrug-resistant Gram-negative (MDR-GRN) bacterial infections. Despite the longstanding utility of colistin, the complexities surrounding polymyxins in terms of resistance mechanisms and pharmacological properties warrant critical attention. This review consolidates current literature, focusing on polymyxins antibacterial mechanisms, resistance pathways, and innovative strategies to mitigate resistance. We are also investigating the pharmacokinetics of polymyxins to elucidate factors that influence their in vivo behavior. A comprehensive understanding of these aspects is pivotal for developing next-generation antimicrobials and optimizing therapeutic regimens. We underscore the urgent need for advancing research on polymyxins to ensure their continued efficacy against formidable bacterial challenges.
Enhancing plant resilience: arbuscular mycorrhizal fungi’s role in alleviating drought stress in vegetation concrete
Authors: Guo Shiwei , Xia Lu , Xia Dong , Li Mingyi , Xu Wennian , Liu Liming
Published: June 2024

Introduction

Drought stress usually inhibits plant growth, which may increase the difficulty of greening slopes.

Methods

In this study, we systematically investigated the effects of arbuscular mycorrhizal (AM) fungi on the growth and drought tolerance of two plant species, Festuca elata and Cassia glauca, in a vegetation concrete environment by exogenously inoculating AM fungi and setting three drought levels: well water, moderate drought and severe drought. The results showed that plant growth was significantly inhibited under drought stress; however, AM fungi inoculation significantly promoted plant height, root length, and above- and belowground biomass in these two plant species.

Results

Compared with, those in the CK treatment, the greatest increases in the net photosynthesis rate, stomatal conductance and transpiration rate in the AM treatment group were 36.72%, 210.08%, and 66.41%, respectively. Moreover, inoculation with AM fungi increased plant superoxide dismutase and catalase activities by 4.70–150.73% and 9.10–95.70%, respectively, and reduced leaf malondialdehyde content by 2.79–55.01%, which alleviated the damage caused by oxidative stress. These effects alleviated the damage caused by oxidative stress and increased the content of soluble sugars and soluble proteins in plant leaves by 1.52–65.44% and 4.67–97.54%, respectively, which further increased the drought adaptability of plants. However, inoculation with AM fungi had different effects on different plants.

Conclusion

In summary, this study demonstrated that the inoculation of AM fungi in vegetation concrete environments can significantly increase plant growth and drought tolerance. The plants that formed a symbiotic structure with AM fungi had a larger root uptake area, greater water uptake capacity, and greater photosynthesis and gas exchange efficiency. In addition, AM fungi inoculation further increased the drought adaptability of the plants by increasing their antioxidant enzyme activity and regulating their metabolite content. These findings are highly important for promoting plant growth and increasing drought tolerance under drought conditions, especially for potential practical applications in areas such as slope protection, and provide useful references for future ecological engineering and sustainable development.