bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspirin reduces the mortality risk of sepsis-associated acute kidney injury: an observational study using the MIMIC IV database
Authors: Chen Sining , Li Shishi , Kuang Chaoying , Zhong Yuzhen , Yang Zhiqian , Yang Yan , Liu Fanna
Published: July 2023

Introduction: Sepsis-associated acute kidney injury (SA-AKI) is a complication of sepsis and is characterized by high mortality. Aspirin affects cyclooxygenases which play a significant role in inflammation, hemostasis, and immunological regulation. Sepsis is an uncontrolled inflammatory and procoagulant response to a pathogen, but aspirin can inhibit platelet function to attenuate the inflammatory response, thus improving outcomes. Several studies have generated contradictory evidence regarding the effect of aspirin on patients with sepsis-associated acute kidney injury (SA-AKI). We conducted an analysis of the MIMIC IV database to investigate the correlation between aspirin utilization and the outcomes of patients with SA-AKI, as well as to determine the most effective dosage for aspirin therapy.

Materials and methods: SA-AKI patients’ clinical data were extracted from MIMIC-IV2.1. Propensity score matching was applied to balance the baseline characteristics between the aspirin group and the non-user group. Subsequently, the relationship between aspirin and patient death was analyzed by Kaplan-Meier method and Cox proportional hazard regression models.

Results: 12,091 patients with SA-AKI were extracted from the MIMIC IV database. In the propensity score-matched sample of 7,694 individuals, lower 90-day mortality risks were observed in the aspirin group compared to the non-users group (adjusted HR: 0.722; 95%CI: 0.666, 0.783) by multivariable cox proportional hazards analysis. In addition, the Kaplan-Meier survival curves indicated a superior 90-day survival rate for aspirin users compared to non-users (the log-rank test p-value was 0.001). And the median survival time of patients receiving aspirin treatment was significantly longer than those not receiving (46.47 days vs. 24.26 days). In the aspirin group, the average ICU stay length was shorter than non-users group. (5.19 days vs. 5.58 days, p = 0.006). There was no significant association between aspirin and an increased risk of gastrointestinal hemorrhage (p = 0.144).

Conclusion: Aspirin might reduce the average ICU stay duration and the 30-day or 90-day mortality risks of SA-AKI patients. No statistically significant difference in the risk of gastrointestinal hemorrhage was found between the aspirin group and the control group.
Cryptotanshinone affects HFL-1 cells proliferation by inhibiting cytokines secretion in RAW264.7 cells and ameliorates inflammation and fibrosis in newborn rats with hyperoxia induced lung injury
Authors: Ma Mengmeng , Bao Tianping , Li Jingyan , Cao Linxia , Yu Bingrui , Hu Jingjing , Cheng Huaiping , Tian Zhaofang
Published: July 2023

Objective: Bronchopulmonary dysplasia (BPD) is a common complication of prematurity and has no specific treatment option. Moreover, inflammation and fibrosis play a vital role in the development of BPD. Thus, this study aimed to explore the role of the anti-inflammatory and anti-fibrotic drug cryptotanshinone (CTS) in the treatment of inflammation and fibrosis in BPD.

Methods:In vivo, Sprague–Dawley rats (male) were divided into air, hyperoxia and CTS groups with different dose interventions (7.5, 15, and 30 mg/kg). A BPD rat model was induced by continuous inhalation of hyperoxia (95%) for 7 days, during which different doses of CTS were injected intraperitoneally. Furthermore, histological examination, hydroxyproline content measurement, Western blot and real-time quantitative polymerase chain reaction were used to detect the levels of inflammation and fibrosis in the tissues. RAW264.7 cells exposed to 95% oxygen were collected and co-cultured with fibroblasts to determine the expression levels of α-SMA, collagen-Ⅰ and MMPs. The levels of pro-inflammatory cytokines such as TNF-α, IL-6 and pro-fibrotic factor TGF-β1 in the supernatants were measured using enzyme-linked immunosorbent assay.

Results: Haematoxylin and eosin staining revealed that CTS reduced the inflammatory response in rat lungs. Masson staining revealed that CTS alleviated the level of pulmonary fibrosis. CTS also reduced the levels of TNF-α, IL-6 and TGF-β1 along with the expression of the fibrosis marker α-SMA in lung tissue. Similarly, in vitro analysis revealed that CTS decreased the levels of TNF-α, IL-6 and TGF-β1 expressed in RAW 264.7 cells, and reduced α-SMA, collagen-Ⅰ, MMPs concentrations in HFL-1 cells co-cultured with the supernatant of RAW264.7 cells after hyperoxia.

Conclusion: CTS can attenuate the hyperoxia-induced inflammatory response and the level of fibrosis by regulating the levels of inflammatory factors and fibrotic factor TGF-β1 expressed by macrophages, thereby highlighting the therapeutic potential of CTS in the treatment of BPD.
Job satisfaction of village doctors in a rural-oriented tuition-waived medical education program in China
Authors: Jin Renmin , Chen Yan
Published: July 2023

Introduction

To address health inequity and relieve shortage of rural doctors, China initiated Rural-oriented Tuition-waived Medical Education (RTME) to train doctors in rural areas for free since 2010. Little is known about job satisfaction of this particular group of rural doctors.

Methods

Job Satisfaction Questionnaires for Village Doctors were distributed to 240 village doctors with RTME program in China, and 40 received in-depth semi-structured interviews. Descriptive analysis, chi-square test, univariate and multivariate logistic regressions in SPSS23.0 were conducted, and thematic analysis was applied to interviews.

Results

Job satisfaction rate of village doctors with RTME program was 56.50%. Full understanding of RTME policy, recognition of rural medical work, relevance of RTME curriculum with present job, education background, rural origin and renumeration were positively correlated with job satisfaction. Preferential policies of RTME program, relaxing working atmosphere, more promotion opportunity, and easier access to higher technical titles were the key factors to retain rural doctors.

Conclusion

Our findings may interest healthcare authorities, medical colleges and primary healthcare establishments. Studying the job satisfaction of village doctors in China may also be beneficial in developing community and rural health services, and provide valuable insights into the training and retention of primary healthcare providers in other countries.
Burden and patient characteristics associated with repeat consultation for unscheduled care within 30 days in primary care: a retrospective case control study with implications for aging and public health
Authors: Richard Valentin , Bouazzi Leila , Richard Clément , Sanchez Stéphane
Published: July 2023

Introduction

Repeated consultations in primary care represent a significant burden on healthcare services. Characterizing the patients who repeatedly attend ambulatory care would enhance our understanding of the healthcare needs of this population, with a view to providing appropriate services. The aim of this study was therefore to identify the factors associated with repeated consultation in unscheduled care. Our secondary aim was to explore the specific profile of patients aged >65 years.

Methods

A retrospective case–control study comparing re-consultation within 30 days at a primary care facility versus non-reconsulting patients, defined as those who did not reconsult within 30 days, among patients consulting over a period of 1 year (1 January to 31 December 2019). Data was collected for a random sample of 5,059 consultations. Patients and controls were matched for age ± 5 years, and sex.

Results

The main factors associated with repeat consultation were an initial consultation late at night (midnight to 6.00 am; OR 1.31, 95%CI 1.20–1.44), and psychological disorders as the main diagnosis (OR 1.33, 95%CI 1.20–1.48). Conversely, consulting at the weekend was associated with a lower likelihood of repeat consultation (OR 0.82, 95% 0.85–0.91).

Conclusion

30-day reconsultations were significantly more frequent after late night consultation. This could be used as an indicator of the quality of care to assess performance of general practice teams with implications for improving overall health of an aging population.
Chat agents respond more empathetically by using hearsay experience
Authors: Narimatsu Hiromi , Sugiyama Hiroaki , Mizukami Masahiro , Arimoto Tsunehiro
Published: July 2023

As the responses of chat dialogue systems have become more natural, the empathy skill of dialogue systems has become an important new issue. In text-based chat dialogue systems, the definition of empathy is not precise, and how to design the kind of utterance that improves the user’s impression of receiving empathy is not clear since the main method used is to imitate utterances and dialogues that humans consider empathetic. In this study, we focus on the necessity of grasping an agent as an experienceable Other, which is considered the most important factor when empathy is performed by an agent, and propose an utterance design that directly conveys the fact that the agent can experience and feel empathy through text. Our system has an experience database including the system’s pseudo-experience and feelings to show empathetic feelings. Then, the system understands the user’s experiences and empathizes with the user on the basis of the system’s experience database, in line with the dialogue content. As a result of developing and evaluating several systems with different ways of conveying the aforementioned rationale, we found that conveying the rationale as a hearsay experience improved the user’s impression of receiving empathy more than conveying it as the system’s own experience. Moreover, an exhaustive evaluation shows that our empathetic utterance design using hearsay experience is effective to improve the user’s impression about the system’s cognitive empathy.
Animals Helping Animals: How Dog Detectives Can Help Save Endangered Species
Authors: Burrows Hannah M. R. , McCreary Maeve K. , Shore Montana J. , Pinheiro Sylvia G. V. , Kuhlmeier Valerie A.
Published: July 2023

Dogs are working alongside humans to help protect animals in the wild that are endangered. People who work in the field of animal conservation can train dogs to use their powerful noses to sniff out where certain endangered species have been. Dogs help their human handlers by finding the scat (poop!) that members of an endangered species have left behind. Scat contains important information about these species that help us preserve their populations. In this article, you will learn why some animals are endangered, why studying scat is so important, and how teams of dogs and humans can work together to find scat.
What Is an Emotion?
Authors: Mohiyeddini Changiz , Baker Stephanie
Published: July 2023

Many moments make up a day. There may be times when we feel happy and other times when we feel sad. But what is really happening when we say we “feel” something? What is an emotion? This article explores this important question. Maybe this question seems simple, but it is actually very complicated. What do we know about emotions? Why do we have emotions at all? Are emotions good or bad? By asking these questions, we join thousands of other scientists and researchers in search of answers. Since all humans have emotions, this is certainly a topic that matters to us all.
Effects of essential mineral elements deficiency and supplementation on serum mineral elements concentration and biochemical parameters in grazing Mongolian sheep
Authors: Jin Xiwei , Meng Lingbo , Zhang Rui , Tong Mengjie , Qi Zhi , Mi Lan
Published: July 2023

Traditional sheep grazing is the pillar industry and the main source of income for local herders in the Inner Mongolia Autonomous Region of China. However, grazing sheep often suffer from mineral deficiency. In the present study, the feeding experiment was performed on 84 grazing Wu Ranke sheep. After being divided into calcium (Ca), zinc (Zn), copper (Cu), cobalt (Co), manganese (Mn), and selenium (Se) treatment groups, they were fed with a mineral deficient diet for 60 days and then a mineral supplement diet for 41 days. Serum samples were collected three times, 10 concentrations of essential mineral elements and 15 concentrations/activity of biochemical parameters were measured to assess the effects of mineral deficiency and supplementation on the physical health of sheep. The results revealed that the sheep showed mineral Ca, Cu, Co, Mn, and Se deficiencies after feeding their respective mineral deficient diet. Deficiency in dietary Ca, Zn, Cu, Co, Mn, and Se may adversely affect the liver, myocardium and pancreas of sheep. The prompt supplementation of dietary Zn, Cu, Co, Mn, and Se may alleviate the damage caused to the liver, myocardium and pancreas, while that of dietary Ca improved energy generation. In conclusion, the adequate supplementation of dietary Ca, Zn, Cu, Co, Mn, and Se is essential for avoiding the impairment caused to the liver, myocardium and pancreas function of sheep by the deficiency in essential dietary minerals.
Applied Techniques for Twitter Data Retrieval in an Urban Area: Insight for Trip Production Modeling
Authors: Rayat Rempu Sora , Dwicaksono Adenantera , Putro Heru P. H. , Dirgahayani Puspita
Published: July 2023

This paper presents methods of retrieving Twitter data, both streaming and archive data, using Application Programming Interfaces. Twitter data are a kind of Location Based Social Network Data that, nowadays, is emerging in transportation demand modeling. Data regarding the locations of trip makers represent the most crucial step in the modeling. No research article has specifically addressed this topic with an up-to-date method; hence, this paper aims to refresh methods for retrieving Twitter data that can capture relevant data. The method is unique as the data are gathered for trip production modeling in zonal urban areas. Python script programs were built for both data retrieving methods. The programs were run for streaming data from May 2020 to April 2021 and archive data from 2018. The data were collected within Serang City, which is the nearest provincial city to Jakarta, the capital of Indonesia. In order to gather streaming data with no loss, the program has been run with referencing on sub-district office coordinate locations. Retrieving the intended data produces 1,090,623 documents, of which 54,103 are geotagged data from 2495 users. The study concluded that streaming data produce more geolocation data, while historical data capture more Twitter user data with relatively very little geotagged data and greater textual data than the period covered in this research. Thus, both techniques of retrieving Twitter data for urban personal trip modeling are necessary. Obtaining sufficient data collection using data streaming retrieval resulted in the most effective data preprocessing. This research contributes to Location Based Social Network data mining knowledge, both geolocation and text mining, and is useful for insight into developing trip production modeling in passenger transportation demand modeling using Machine Learning. This study also aims to provide useful methods for transportation system researchers and data scientists in utilizing Location Based Social Network data.
Change of Competences in the Context of Industry 4.0 Implementation
Authors: Szabó Peter , Mĺkva Miroslava , Marková Petra , Samáková Jana , Janík Samuel
Published: July 2023

Industry 4.0 will not only change what we are and what we do, but also who we are. As a result of the rapid introduction of new technologies, which is characteristic for Industry 4.0, there will be a change in the labour market. It allows people, things and machines to be connected in real time, thus ensuring that the necessary information is exchanged between them. There are advantages, but also negatives: one of the impacts of Industry 4.0 is the gradual transformation of the labour market, leading to a demand for new professional skills and the digitalisation of work. Thus, it brings with it the need for employees to adapt to the changing sub-conditions of the labour market. The aim of this article is to identify and highlight the need for changes in the field of competences in connection with the application of Industry 4.0 methods and techniques. For the purpose of this research, a valid data collection instrument (questionnaire for the research) was developed and distributed to enterprises in the field of selected industry sectors in the Slovak Republic. In total, the research sample consisted of n = 556 respondents. On the basis of the obtained results, we conclude that early identification of future needs in terms of competences gives the possibility of setting up training activities aimed at acquiring new, missing and needed-for-the-future competences of employees.
Assessment of Load-Bearing Timber Elements for the Design for Disassembly
Authors: Laasonen Sonja , Pajunen Sami
Published: July 2023

This literature review examined the functionality of the connection or connections and disassembly as a general strategy. The prerequisites that arose for disassembly were, among other things, damage tolerance, reduction of emissions compared to raw materials, costs, and guaranteeing safety. The set of criteria for disassembly was defined from the structural engineers’ perspective through the literature review. The criteria focus on joints, which are key to the success of disassembly. Five different criteria were used to evaluate joints in this study. The criteria were ease of access to components, ease of disassembly, independence, simplicity, and standardization. The evaluation was executed for different widely used connections in timber constructions. The criteria were evaluated subjectively from one to four. As a conclusion, the load-bearing timber elements have a promising future in design for disassembly. Design for disassembly aims to promote reuse and other features to increase the life cycle of structural elements. It has the potential to reduce the usage of raw materials and significantly decrease the emissions of construction.
Influence of the Absolute Pressure of the Extraction System on the Yield and Composition of Corymbia citriodora (Hook.) K.D.Hill and L.A.S.Johnson Leaf Essential Oil Extracted by Steam Distillation
Authors: de Araujo Juliana , Silvestre Wendel Paulo , Pauletti Gabriel Fernandes , Muniz Luis Antonio Rezende
Published: July 2023

This study aimed to evaluate the extraction of Corymbia citriodora (Hook.) K.D.Hill and L.A.S.Johnson essential oil by steam distillation under reduced pressure. Yield and composition of the essential oils obtained at different system pressures were analyzed. System pressure had a significant influence on essential oil yield, resulting in a reduction of 78.6% when the pressure was reduced from 690 Torr to 240 Torr. There were also changes in essential oil composition, with an increase in citronellol content (oxygenated monoterpene). However, the major compound (citronellal) remained at a high content in all tests. Regarding the extracted mass of the major compounds (citronellal, citronellol), there was a significant reduction for all when the system pressure was reduced. Although the reduction in the pressure of the system caused a reduction in oil yield, it was possible to carry out the steps of extraction and purification of the major compound simultaneously. Reduced pressure extraction may decrease process time, increasing its efficiency and reducing costs in the extraction of essential oils.
Kernel-Free Quadratic Surface Regression for Multi-Class Classification
Authors: Wang Changlin , Yang Zhixia , Ye Junyou , Yang Xue
Published: July 2023

For multi-class classification problems, a new kernel-free nonlinear classifier is presented, called the hard quadratic surface least squares regression (HQSLSR). It combines the benefits of the least squares loss function and quadratic kernel-free trick. The optimization problem of HQSLSR is convex and unconstrained, making it easy to solve. Further, to improve the generalization ability of HQSLSR, a softened version (SQSLSR) is proposed by introducing an ε-dragging technique, which can enlarge the between-class distance. The optimization problem of SQSLSR is solved by designing an alteration iteration algorithm. The convergence, interpretability and computational complexity of our methods are addressed in a theoretical analysis. The visualization results on five artificial datasets demonstrate that the obtained regression function in each category has geometric diversity and the advantage of the ε-dragging technique. Furthermore, experimental results on benchmark datasets show that our methods perform comparably to some state-of-the-art classifiers.
Reasoning and Logical Proofs of the Fundamental Laws: “No Hope” for the Challengers of the Second Law of Thermodynamics
Authors: Kostic Milivoje
Published: July 2023

This comprehensive treatise is written for the special occasion of the author’s 70th birthday. It presents his lifelong endeavors and reflections with original reasoning and re-interpretations of the most critical and sometimes misleading issues in thermodynamics—since now, we have the advantage to look at the historical developments more comprehensively and objectively than the pioneers. Starting from Carnot (grand-father of thermodynamics to become) to Kelvin and Clausius (fathers of thermodynamics), and other followers, the most relevant issues are critically examined and put in historical and contemporary perspective. From the original reasoning of generalized “energy forcing and displacement” to the logical proofs of several fundamental laws, to the ubiquity of thermal motion and heat, and the indestructibility of entropy, including the new concept of “thermal roughness” and “inevitability of dissipative irreversibility,” to dissecting “Carnot true reversible-equivalency” and the critical concept of “thermal-transformer,” limited by the newly generalized “Carnot-Clausius heat-work reversible-equivalency (CCHWRE),” regarding the inter-complementarity of heat and work, and to demonstrating “No Hope” for the “Challengers” of the Second Law of thermodynamics, among others, are offered. It is hoped that the novel contributions presented here will enlighten better comprehension and resolve some of the fundamental issues, as well as promote collaboration and future progress.
Kolmogorov Entropy for Convergence Rate in Incomplete Functional Time Series: Application to Percentile and Cumulative Estimation in High Dimensional Data
Authors: Litimein Ouahiba , Alshahrani Fatimah , Bouzebda Salim , Laksaci Ali , Mechab Boubaker
Published: July 2023

The convergence rate for free-distribution functional data analyses is challenging. It requires some advanced pure mathematics functional analysis tools. This paper aims to bring several contributions to the existing functional data analysis literature. First, we prove in this work that Kolmogorov entropy is a fundamental tool in characterizing the convergence rate of the local linear estimation. Precisely, we use this tool to derive the uniform convergence rate of the local linear estimation of the conditional cumulative distribution function and the local linear estimation conditional quantile function. Second, a central limit theorem for the proposed estimators is established. These results are proved under general assumptions, allowing for the incomplete functional time series case to be covered. Specifically, we model the correlation using the ergodic assumption and assume that the response variable is collected with missing at random. Finally, we conduct Monte Carlo simulations to assess the finite sample performance of the proposed estimators.
Electrochemical Properties of Sputtered Ruthenium Oxide Neural Stimulation and Recording Electrodes
Authors: Chakraborty Bitan
Published: July 2023

A chronically stable electrode material with a low impedance for recording neural activity, and a high charge-injection capacity for functional electro-stimulation is desirable for the fabrication of implantable microelectrode arrays that aim to restore impaired or lost neurological functions in humans. For this purpose, we have investigated the electrochemical properties of sputtered ruthenium oxide (RuOx) electrode coatings deposited on planar microelectrode arrays, using an inorganic model of interstitial fluid (model-ISF) at 37 °C as the electrolyte. Through a combination of cyclic voltammetry (CV) and an electrochemical impedance spectroscopy (EIS) modelling study, we have established the contribution of the faradaic reaction as the major charge-injection contributor within the safe neural stimulation potential window of ±0.6 V vs. Ag|AgCl. We have also established the reversibility of the charge-injection process for sputtered RuOx film, by applying constant charge-per-phase current stimulations at different pulse widths, and by comparing the magnitudes of the leading and trailing access voltages during voltage transient measurements. Finally, the impedance of the sputtered RuOx film was found to be reasonably comparable in both its oxidized and reduced states, although the electronic contribution from the capacitive double-layer was found to be slightly higher for the completely oxidized film around 0.6 V than for its reduced counterpart around −0.6 V.
Effect of Electro-Oil Acclimation of an Indigenous Strain on the Performance of Sediment Microbial Fuel Cells (SMFC)
Authors: Pan Yao , Tang Shanfa , Ren Wen , Cheng Yuanpeng , Gao Jie , Huang Chunfeng , Fu Ke
Published: July 2023

Sediment microbial fuel cell (SMFC) is a type of MFC without a proton exchange membrane. However, SMFC have had problems with low-power production performance. In this paper, the effects of native bacteria (K1) in oily sludge and their electro-oil-induced domestication on the power generation and oil removal performance of SMFC were studied. The results showed that K1 belonged to Ochrobactrum intermedium. During the domestication process, an upward trend was shown in the OD600 and ORP values in the culture medium, and it grown best at 0.7 V. Ochrobactrum intermedium K1 significantly increased the average output voltage, electromotive force, and maximum power density of SMFC and reduced the apparent internal resistance of the battery. The maximum power density was 169.43 mW/m3, which was 8.59 times higher than that of the control group. Ochrobactrum intermedium K1 improved the degradation of crude oil by SMFC. Ochrobactrum intermedium K1 enhanced the degradation of high-carbon alkanes and even-carbon alkanes in n-alkanes. Cyclic voltammetry and chronoamperometry tests showed that after acclimation, Ochrobactrum intermedium K1 improved the extracellular electron transfer efficiency (EET) mediated by c-Cyts and flavin by increasing the surface protein redox potential.
Epigenetic Regulation in Heterosis and Environmental Stress: The Challenge of Producing Hybrid Epigenomes to Face Climate Change
Authors: Duarte-Aké Fátima , Us-Camas Rosa , De-la-Peña Clelia
Published: July 2023

Epigenetic regulation has the potential to revolutionize plant breeding and improve crop yields by regulating gene expression in plants. DNA methylation and histone modifications are key epigenetic modifications that can impact plant development, stress responses, productivity, and yields. Higher-yielding crops not only generate greater profits for farmers and seed producers, but also require less land, water, fuel, and fertilizer than traditional crops for equivalent yields. The use of heterosis in crops can influence productivity and food quality, but producing hybrids with superior agronomic traits to their parents remains challenging. However, epigenetic markers, such as histone methylation and acetylation, may help select parental and hybrid combinations with better performances than the parental plants. This review assesses the potential applications of epigenetics in crop breeding and improvement, rendering agriculture more efficient, sustainable, and adaptable to changing environmental conditions.
Elucidating Quadruplication Event of PHO1 Gene: A Key Regulator of Plant Phosphate Translocation in Brassica rapa
Authors: Shahbuddin Dahlia , Rusly Rosazlina , Shuid Ahmad Naqib , Ahmad Khair Ahmad Bukhary
Published: July 2023

In response to Pi deprivation, phosphate 1 (PHO1) is a significant regulator at trans-eQTL hotspots in Brassica rapa. Brassica rapa short-read sequencing data analysis revealed four PHO1 paralog genes, PHO1_A, PHO1_B, PHO1_C, and PHO1_D, placed in tandem with very high sequence similarity. However, based on short-read genomic sequence data, only three transcripts are accessible. Five bacterial artificial chromosomes (BACs) can be sequenced using a long-read sequencer, which improves de novo assembly and identifies structural variants. The PHO1 gene’s quadruplicating tandem positions in the genomic sequence were confirmed by an analysis of long-read data. Transcript analysis identified only three groups of PHO1 paralogs (ortholog AT1G14040 in Arabidopsis), i.e., PHO1_A, PHO1_B, and PHO1_D, expressed in B. rapa leaf tissues under Pi deficiency. PHO1_A, with transcript ID XM_009150437.2, has five different splice variants found. These splice variants’ truncated proteins demonstrated PHO1_A’s function in P control as opposed to protein encoding.
Tea Polyphenols Protects Tracheal Epithelial Tight Junctions in Lung during Actinobacillus pleuropneumoniae Infection via Suppressing TLR-4/MAPK/PKC-MLCK Signaling
Authors: Li Xiaoyue , Liu Zewen , Gao Ting , Liu Wei , Yang Keli , Guo Rui , Li Chang , Tian Yongxiang , Wang Ningning , Zhou Danna , Bei Weicheng , Yuan Fangyan
Published: July 2023

Actinobacillus pleuropneumoniae (APP) is the causative pathogen of porcine pleuropneumonia, a highly contagious respiratory disease in the pig industry. The increasingly severe antimicrobial resistance in APP urgently requires novel antibacterial alternatives for the treatment of APP infection. In this study, we investigated the effect of tea polyphenols (TP) against APP. MIC and MBC of TP showed significant inhibitory effects on bacteria growth and caused cellular damage to APP. Furthermore, TP decreased adherent activity of APP to the newborn pig tracheal epithelial cells (NPTr) and the destruction of the tight adherence junction proteins β-catenin and occludin. Moreover, TP improved the survival rate of APP infected mice but also attenuated the release of the inflammation-related cytokines IL-6, IL-8, and TNF-α. TP inhibited activation of the TLR/MAPK/PKC-MLCK signaling for down-regulated TLR-2, TLR4, p-JNK, p-p38, p-PKC-α, and MLCK in cells triggered by APP. Collectively, our data suggest that TP represents a promising therapeutic agent in the treatment of APP infection.
Intranasally Administered MSC-Derived Extracellular Vesicles Reverse Cisplatin-Induced Cognitive Impairment
Authors: Milutinovic Bojana , Mahalingam Rajasekaran , Mendt Mayela , Arroyo Luis , Seua Alexandre , Dharmaraj Shruti , Shpall Elizabeth , Heijnen Cobi J.
Published: July 2023

Neurotoxic side effects of chemotherapy include deficits in attention, memory, and executive functioning. Currently, there are no FDA-approved therapies. In mice, cisplatin causes long-term cognitive deficits, white matter damage, mitochondrial dysfunction, and loss of synaptic integrity. We hypothesized that MSC-derived small extracellular vesicles (sEVs) could restore cisplatin-induced cognitive impairments and brain damage. Animals were injected with cisplatin intraperitoneally and treated with MSC-derived sEVs intranasally 48 and 96 h after the last cisplatin injection. The puzzle box test (PBT) and the novel object place recognition test (NOPRT) were used to determine cognitive deficits. Synaptosomal mitochondrial morphology was analyzed by transmission electron microscopy. Immunohistochemistry using antibodies against synaptophysin and PSD95 was applied to assess synaptic loss. Black-Gold II staining was used to quantify white matter integrity. Our data show that sEVs enter the brain in 30 min and reverse the cisplatin-induced deficits in executive functioning and working and spatial memory. Abnormalities in mitochondrial morphology, loss of white matter, and synaptic integrity in the hippocampus were restored as well. Transcriptomic analysis revealed upregulation of regenerative functions after treatment with sEVs, pointing to a possible role of axonal guidance signaling, netrin signaling, and Wnt/Ca2+ signaling in recovery. Our data suggest that intranasal sEV treatment could become a novel therapeutic approach for the treatment of chemobrain.
Hyperacusis in the Adult Fmr1-KO Mouse Model of Fragile X Syndrome: The Therapeutic Relevance of Cochlear Alterations and BKCa Channels
Authors: Ferraguto Celeste , Bouleau Yohan , Peineau Thibault , Dulon Didier , Pietropaolo Susanna
Published: July 2023

Hyperacusis, i.e., an increased sensitivity to sounds, is described in several neurodevelopmental disorders (NDDs), including Fragile X Syndrome (FXS). The mechanisms underlying hyperacusis in FXS are still largely unknown and effective therapies are lacking. Big conductance calcium-activated potassium (BKCa) channels were proposed as a therapeutic target to treat several behavioral disturbances in FXS preclinical models, but their role in mediating their auditory alterations was not specifically addressed. Furthermore, studies on the acoustic phenotypes of FXS animal models mostly focused on central rather than peripheral auditory pathways. Here, we provided an extensive characterization of the peripheral auditory phenotype of the Fmr1-knockout (KO) mouse model of FXS at adulthood. We also assessed whether the acute administration of Chlorzoxazone, a BKCa agonist, could rescue the auditory abnormalities of adult mutant mice. Fmr1-KO mice both at 3 and 6 months showed a hyperacusis-like startle phenotype with paradoxically reduced auditory brainstem responses associated with a loss of ribbon synapses in the inner hair cells (IHCs) compared to their wild-type (WT) littermates. BKCa expression was markedly reduced in the IHCs of KOs compared to WT mice, but only at 6 months, when Chlorzoxazone rescued mutant auditory dysfunction. Our findings highlight the age-dependent and progressive contribution of peripheral mechanisms and BKCa channels to adult hyperacusis in FXS, suggesting a novel therapeutic target to treat auditory dysfunction in NDDs.
Recent Progress in the Characterization, Synthesis, Delivery Procedures, Treatment Strategies, and Precision of Antimicrobial Peptides
Authors: Bakare Olalekan Olanrewaju , Gokul Arun , Niekerk Lee-Ann , Aina Omolola , Abiona Ademola , Barker Adele Mariska , Basson Gerhard , Nkomo Mbukeni , Otomo Laetitia , Keyster Marshall , Klein Ashwil
Published: July 2023

Infectious diseases are constantly evolving to bypass antibiotics or create resistance against them. There is a piercing alarm for the need to improve the design of new effective antimicrobial agents such as antimicrobial peptides which are less prone to resistance and possess high sensitivity. This would guard public health in combating and overcoming stubborn pathogens and mitigate incurable diseases; however, the emergence of antimicrobial peptides’ shortcomings ranging from untimely degradation by enzymes to difficulty in the design against specific targets is a major bottleneck in achieving these objectives. This review is aimed at highlighting the recent progress in antimicrobial peptide development in the area of nanotechnology-based delivery, selectivity indices, synthesis and characterization, their doping and coating, and the shortfall of these approaches. This review will raise awareness of antimicrobial peptides as prospective therapeutic agents in the medical and pharmaceutical industries, such as the sensitive treatment of diseases and their utilization. The knowledge from this development would guide the future design of these novel peptides and allow the development of highly specific, sensitive, and accurate antimicrobial peptides to initiate treatment regimens in patients to enable them to have accommodating lifestyles.
Sarcospan Deficiency Increases Oxidative Stress and Arrhythmias in Hearts after Acute Ischemia-Reperfusion Injury
Authors: Hwang Hyun Seok , Kahmini Aida Rahimi , Prascak Julia , Cejas-Carbonell Alexis , Valera Isela C. , Champion Samantha , Corrigan Mikayla , Mumbi Florence , Parvatiyar Michelle S.
Published: July 2023

The protein sarcospan (SSPN) is an integral member of the dystrophin-glycoprotein complex (DGC) and has been shown to be important in the heart during the development and the response to acute stress. In this study, we investigated the role of SSPN in the cardiac response to acute ischemia-reperfusion (IR) injury in SSPN-deficient (SSPN−/−) mice. First, the hemodynamic response of SSPN−/− mice was tested and was similar to SSPN+/+ (wild-type) mice after isoproterenol injection. Using the in situ Langendorff perfusion method, SSPN−/− hearts were subjected to IR injury and found to have increased infarct size and arrhythmia susceptibility compared to SSPN+/+. Ca2+ handling was assessed in single cardiomyocytes and diastolic Ca2+ levels were increased after acute β-AR stimulation in SSPN+/+ but not SSPN−/−. It was also found that SSPN−/− cardiomyocytes had reduced Ca2+ SR content compared to SSPN+/+ but similar SR Ca2+ release. Next, we used qRT-PCR to examine gene expression of Ca2+ handling proteins after acute IR injury. SSPN−/− hearts showed a significant decrease in L-type Ca2+ channels and a significant increase in Ca2+ release channel (RyR2) expression. Interestingly, under oxidizing conditions reminiscent of IR, SSPN−/− cardiomyocytes, had increased H2O2-induced reactive oxygen species production compared to SSPN+/+. Examination of oxidative stress proteins indicated that NADPH oxidase 4 and oxidized CAMKII were increased in SSPN−/− hearts after acute IR injury. These results suggest that increased arrhythmia susceptibility in SSPN−/− hearts post-IR injury may arise from alterations in Ca2+ handling and a reduced capacity to regulate oxidative stress pathways.
The Role of Multimodality Imaging in Pediatric Cardiomyopathies
Authors: Moscatelli Sara , Leo Isabella , Bianco Francesco , Borrelli Nunzia , Beltrami Matteo , Garofalo Manuel , Milano Elena , Bisaccia Giandomenico , Iellamo Ferdinando , Bassareo Pier , Pradhan Akshyaya , Cimini Andrea , Perrone Marco
Published: July 2023

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause of heart transplantation in children. Diagnosing and classifying the different phenotypes can be challenging, particularly in this age group, where cardiomyopathies are often overlooked until the onset of severe symptoms. Cardiovascular imaging is crucial in the diagnostic pathway, from screening to classification and follow-up assessment. Several imaging modalities have been proven to be helpful in this field, with echocardiography undoubtedly representing the first imaging approach due to its low cost, lack of radiation, and wide availability. However, particularly in this clinical context, echocardiography may not be able to differentiate from cardiomyopathies with similar phenotypes and is often complemented with cardiovascular magnetic resonance. The latter allows a radiation-free differentiation between different phenotypes with unique myocardial tissue characterization, thus identifying the presence and extent of myocardial fibrosis. Nuclear imaging and computed tomography have a complementary role, although they are less used in daily clinical practice due to the concern related to the use of radiation in pediatric patients. However, these modalities may have some advantages in evaluating children with cardiomyopathies. This paper aims to review the strengths and limitations of each imaging modality in evaluating pediatric patients with suspected or known cardiomyopathies.
PET/CT and SPECT/CT Imaging of HER2-Positive Breast Cancer
Authors: McGale Jeremy , Khurana Sakshi , Huang Alice , Roa Tina , Yeh Randy , Shirini Dorsa , Doshi Parth , Nakhla Abanoub , Bebawy Maria , Khalil David , Lotfalla Andrew , Higgins Hayley , Gulati Amit , Girard Antoine , Bidard Francois-Clement , Champion Laurence , Duong Phuong , Dercle Laurent , Seban Romain-David
Published: July 2023

HER2 (Human Epidermal Growth Factor Receptor 2)-positive breast cancer is characterized by amplification of the HER2 gene and is associated with more aggressive tumor growth, increased risk of metastasis, and poorer prognosis when compared to other subtypes of breast cancer. HER2 expression is therefore a critical tumor feature that can be used to diagnose and treat breast cancer. Moving forward, advances in HER2 in vivo imaging, involving the use of techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), may allow for a greater role for HER2 status in guiding the management of breast cancer patients. This will apply both to patients who are HER2-positive and those who have limited-to-minimal immunohistochemical HER2 expression (HER2-low), with imaging ultimately helping clinicians determine the size and location of tumors. Additionally, PET and SPECT could help evaluate effectiveness of HER2-targeted therapies, such as trastuzumab or pertuzumab for HER2-positive cancers, and specially modified antibody drug conjugates (ADC), such as trastuzumab-deruxtecan, for HER2-low variants. This review will explore the current and future role of HER2 imaging in personalizing the care of patients diagnosed with breast cancer.
Whole Body Substrate Metabolism during Different Exercise Intensities with Special Emphasis on Blood Protein Changes in Trained Subjects—A Pilot Study
Authors: Mekonen Wondyefraw , Schwaberger Günther , Lamprecht Manfred , Hofmann Peter
Published: July 2023

Contrary to carbohydrate and fat metabolism, the influence of a single exercise dose on protein metabolism has not been adequately explored yet. We assessed the effects of different exercise intensities and durations on blood protein changes and their association with carbohydrate (CHO) and fat metabolism in six eligible trained subjects. Subjects performed maximal incremental (IE100: at 100%VO2max) and submaximal continuous exercise (CE) at 75%VO2max for 30 min (CE75) and at 50%VO2max for 90 min (CE50). Blood samples were collected at rest (R), end of exercise (EE), and 1 h after recovery to assess blood urea nitrogen (BUN), plasma amino acids (AA), glucose, lactate, FFA, and glycerol. In IE100 blood lactate, CHO-oxidation (g/min), energy expenditure (kcal/min), and RER were significantly increased during rest (p < 0.05). CE50 induced significantly higher BUN, FFA, glycerol, and fat oxidation (g/min) (p < 0.05). At recovery, the mean sum of the free AA pool (µmol/L) reduced by 8% (p < 0.03) during CE50. Values for CE75 were between IE100 and CE50. Beside lipolysis, also proteolysis (BUN) was an important source of fuel for low-to-moderate intensity CE50. An increased uptake of AA from the plasma bed during CE50 suggests the importance for oxidation and synthesis of other metabolic sources such as gluconeogenesis necessary for recovery. Therefore, one needs to be cautious of protein diet following prolonged cycle exercise training.
Assessment of the Vulnerability of the Coast of Lake Alakol to Modern Geomorphological Processes of Relief Formation
Authors: Medeu Akhmetkal , Valeyev Adilet , Akiyanova Farida , Lyy Yuisya , Issanova Gulnura , Ge Yongxiao
Published: July 2023

Over the last few decades, increasing water levels of Lake Alakol have led to the activation of processes of modern relief formation of the coastal territory. This study will make it possible to assess the vulnerability of the lake shore to modern relief-forming processes, which pose a threat to the economic and infrastructural development of the coast. Through a combination of field research methods, analysis of the archival materials and satellite images, GIS mapping, as well as the application of the Coastal Vulnerability Index, developed by Gornitz, a map of the modern relief of the coast of Lake Alakol was created, where 13 geomorphological types of relief were identified, and a map of relief-forming processes and leading exogenous processes were identified. The values of the assessment of the degree of vulnerability of the coast to dangerous processes by the Gornitz method were obtained, where a high vulnerability covers 67.4% of the coast, an average vulnerability covers 2.9%, a weak vulnerability covers 13.3%, and low vulnerability occupies 16.4% of the coast. The degree of vulnerability of types of relief in the study area, the coast of Lake Alakol, was determined. High degree occupies 42.8% of the study area, medium—30.7%, weak—25.4%, and low 1.1%. A map of the complex assessment of the degree of vulnerability of the coast of Lake Alakol was created. It was revealed that low accumulative types of relief of the northwest and northeast coasts and alluvial-proluvial types of relief are highly vulnerable due to waterlogging and the intensity of abrasion processes. Identified natural features of the relief formation of the coast of Lake Alakol are recommended as a basis for making decisions on the planning and implementation of any economic activities on the coast, including infrastructure development of the coast and strengthening of the shores.
On Actuality Entailments, Causation, and Telicity in Balkar
Authors: Privoznov Dmitry
Published: July 2023

This paper presents a study of actuality entailments in Balkar (a dialect of Karachay-Balkar, Turkic). The study focuses on the deontic and causal meanings of four morphemes: two suffixes (the causative suffix and the suffix -al (‘can/may’)) and two verbs (bujur (‘order’) and qoj (‘allow’)). In the first half of the paper, I provide empirical support for three generalizations: (a) only causal modals can have actuality entailments (all universal and some existential causal modals); (b) actuality entailments arise whenever a causal modal has a telic interpretation, more precisely, when it is not embedded under an imperfective or a delimitative operator (c) existential but not universal causal modals trigger an anti-actuality entailment under negation. In the second half of the paper, I propose a theory of root modality within the framework of situation semantics. In this framework, root modals describe a situation (the anchor situation) and quantify over situations that stand in a particular semantic relation to it. The proposed Causal Modality Theory (CMT) consists of two assumptions: (a) Causal modals quantify over causal chains initiated by the counterparts of the anchor situation. (b) Some existential causal modals have a conditional presupposition: if any counterpart of the anchor situation caused another situation, then the anchor situation itself caused the same situation. The first assumption explains why all universal causal modals have actuality entailments and why existential causal modals trigger an anti-actuality entailment under negation. The second assumption predicts that some existential causal modals (the ones with the conditional presupposition) also trigger an actuality entailment. CMT treats causal modals as bi-eventive predicates, like (non-culminating) accomplishments. They describe two situations: the anchor situation and a situation caused by it. As a result, causal modals are predicted to behave like (non-culminating) accomplishments, namely, they are predicted to trigger actuality entailments if and only if they are not embedded under an imperfective or a delimitative operator.