bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate Change and Corporate Regulation: A Critical Analysis of Egypt’s Legal and Regulatory Regime
Authors:   Law School, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.  Email: k.o.kila@hud.ac.uk, Kila Kikelomo Oluwaseun
Published: April 2023

Corporations operating in African states generally have apathy to climate change/environmental regulation, owing to their weak economic bargaining strength in these states. Egypt is one of the African states suffering the disproportionate impacts of climate change and although it has drawn up several climate policy documents, it has not yet enacted a Climate Change Act and has a weak regulatory capacity to restrain adverse corporate climate change-impacting activities. This article critically analyses the legal/ regulatory regime in Egypt for regulating corporate participation in climate change mitigation and its effectiveness in addressing climate change challenges. It critically analyses the implementation of the Dilute Interventionism Model. It evaluates the required legislative framework, regulator, and technical expertise necessary for its successful implementation. This paper also highlights the importance of the Veto Firewall protection to maintain the independence of the sole independent regulator responsible for regulating the climate change activities of corporations. This paper argues that the Dilute Interventionism Model, in conjunction with the veto firewall paradigm, provides a practical and effective approach to regulating corporations. However, successful implementation will require political will, corporate compliance, and technical capacity. This paper provides policymakers, stakeholders, and interested parties in Egypt and elsewhere with useful insights for addressing climate change challenges.
Variable Recursive Least Square Algorithm for Lithium-ion Battery Equivalent Circuit Model Parameters Identification
Authors: El Marghichi Mouncef , Loulijat Azedine , El Hantati Issam
Published: April 2023

For SOC (state of charge) assessment techniques based on electrical circuit models, the parameters of the model are strongly biased by: battery aging, temperature, causing some errors in the estimation of the SOC. One approach to solve this problem is to update the model parameters constantly. We suggest a new algorithm VRLS (variable recursive least squares) to update the parameters of a 2-resistor-capacitor (RC) network and to estimate the output battery voltage. VRLS is compared to the recursive least squares (RLS) and the adaptive forgetting factor recursive least squares (AFFRLS) algorithms. For algorithm assessment, we utilized real experimental data conducted on the Samsung 18650-20R lithium-ion cell. The tests indicate that compared to RLS and AFFRLS methods, VRLS recorded a low distribution in the high error range, in addition to small predictive performance indicators (RMSE, MAE, and MAPE) in all tests, which implies that VRLS has a good parameter identification ability.
Developing cartoon based educative mathematics learning media on mathematical representation ability of junior high school students
Authors: Haryadi Rahman , Hartinah Galuh
Published: April 2023

This study aimed to describe the level of validity, practicality, and effectiveness of cartoon film-based educative mathematics learning media on the mathematical representation abilities of junior high school students. This research method was the Research and Development method using the Borg and Gall model. The research subjects were students of class VIII at the Catholic Middle School of Saint Petrus Pontianak. Participants in this study included material expert validators and media expert validators and Class VII E students of St. Petrus Catholic Middle School Pontianak. Tools of data collection used including validation sheets, questionnaires, and test questions. Based on the results of the validation of material experts and media experts, the validity of the material was set at 89.57% with very valid criteria, a practical level of 91.50% with very practical criteria, an effectiveness level of 86.67% with very effective criteria.
Development of tourist travel pattern mathematically in Spermonde islands, South Sulawesi, Indonesia
Authors: Amirullah Amirullah , Rusdi Muhammad , Sarira Matthew Tinna , Djabbar Atriana , Hanafi Hasdar , Sudrajat Yayan
Published: April 2023

Travel patterns destination Region Loop, or a combination of Single Point and Chaining Loopused to go to zone A, zone B, zone C and zone D in the Spermonde archipelago for the purpose of marine tourism activities relation to activities at sea, both above sea level (marine) and activities carried out below sea level (submarine).
Improving the process of occupational risk ­management according to the Haddon matrix
Authors: Tsopa V. A , Cheberiachko S. I , Yavorska O. O , Deryugin O. V , Bilko T. O
Published: April 2023

Purpose. Improving the process of managing occupational risk (OR) in occupational safety and health management systems, due to the distribution of dangerous factors which increase the probability of a dangerous event into several phases: before the occurrence of a dangerous event and after its occurrence. Methodology. The method of morphological analysis is used, which is based on the selection of possible solutions for individual parts of the task based on several morphological typical features important for the problem being solved, and the compilation of all possible combinations of hazardous factors and precautionary measures that will allow reducing the amount of occupational risk. Findings. A new approach to occupational risk management is proposed, which involves the division of all dangerous factors into several phases: before the occurrence of a dangerous event, after its occurrence, provision of pre-medical assistance, provision of emergency and medical care. Typical dangerous factors are defined that increase the probability of the occurrence of a dangerous event, which relate to the first phase (before the occurrence of a dangerous event), as well as dangerous factors that affect the severity of accidents and are characteristic of the second, third and fourth phases (after the occurrence of a dangerous event). A concept was developed for calculating the magnitude of occupational risks, based on the consequences of the occurrence of a dangerous event or by the type of injury with the area of responsibility of the enterprise; from the consequences of pre-medical care or the condition of an injured person with the area of responsibility of the enterprise and with the consequences of emergency and inpatient medical care or the state of loss of health of the employee with the area of responsibility of the medical institution. The hierarchy of preventive measures has been improved due to the addition of protective measures consisting of pre-medical care, emergency medical care, in-patient medical care. Originality. When assessing professional risks, it is proposed to determine the amount in accordance with the area of responsibility of the enterprise and and medical institution taking into account dangerous factors corresponding to a specific phase. Practical value. Examples of three matrices for assessing the occupational risk have been developed, taking into account the classification of the severity of the consequences for the health of the employee, which occurred immediately after the occurrence of a dangerous event (accident), after the provision of pre-medical care and after the provision of emergency and medical care. A description of preventive actions to reduce the severity of the consequences is proposed, taking into account the sphere of responsibility.
Phenol adsorption onto olive pomace activated carbon: modelling and optimization
Authors: Merzeg F. Ait , Bait N , Mokrani T , Akkari I , Ladji R , Bachari K
Published: April 2023

Purpose. To depollute water contaminated by phenol using the adsorption process in a batch reactor with valorization of olive pomace for the preparation of activated carbon to be used as an adsorbent. Methodology. In this present work, study on the influence of four principal parameters on the adsorption yield during the treatment of polluted water by the process of adsorption were studied, namely: the activated carbon mass, the contact time, the phenol initial concentration and the stirring speed. In addition, the process was optimized with full factorial designs using the response surface methodology by the MINITAB software. Findings. The phenol removal by adsorption on the activated carbon made from olive pomace makes it possible to achieve an adsorption efficiency of 91 % with the use of following optimal conditions: adsorbent mass of 0.48 g, a contact time of 110.80 min, a phenol concentration of 100.98 mg/L, and a stirring speed of 462.89 rpm. Contact time and adsorbent mass showed a positive effect on phenol removal efficiency. The principal effect results illustrate that all four examined factors significantly affected the phenol removal by olive pomace activated carbon with a confidence level of 95 %. Originality. The experimental data of the phenol adsorption on the olive pomace activated carbon were examined by adjustment of a second-degree polynomial model. This model is validated by a statistical method using an analysis of variance (­ANOVA). Numerical optimization was performed by the desirability function to identify the optimal parameters for maximum phenol recovery. Practical value. In order to highlight a process for treating waters contaminated with phenol, we have chosen the processes that are considered to be best suited, which is adsorption with the recovery of a waste such as an adsorbent, which is prepared by physical and chemical activation of olive pomace. The full factorial design applied makes it possible to show the influence of each parameter independently and their dependencies, as well as to find the optimal experimental conditions quickly which lead to the realization of this process.
Phản ứng của thị trường chứng khoán Việt Nam trong bối cảnh đại dịch COVID
Authors: Trần Phạm Trác , Lê Thị Thuý Hằng
Published: April 2023

Đại dịch COVID-19 đã ảnh hưởng đến các nền kinh tế trên thế giới. Số lượng ca bệnh gia tăng trên toàn thế giới đã gây ra sự bất ổn của thị trường tài chính mỗi ngày. Những biến động này dẫn đến việc nhiều nền kinh tế chịu tổn thất lớn do sự lây lan của đại dịch. Bài báo này nhằm mục đích nghiên cứu tác động của đại dịch COVID-19 đối với thị trường chứng khoán của Việt Nam. Trong nghiên cứu này, mô hình VECM được sử dụng để nghiên cứu ước tính chuyển động của thị trường chứng khoán trong các giai đoạn của đại dịch COVID-19: giai đoạn đầu, giai đoạn khi lệnh giãn cách xã hội được thực hiện và giai đoạn bình thường mới, khi chính phủ ngừng thực hiện lệnh giãn cách xã hội. Khung thời gian nghiên cứu kéo dài từ ngày 30 tháng 01 năm 2020 đến ngày 29 tháng 06 năm 2022. Kết quả cho thấy đại dịch COVID-19 không còn những tác động tiêu cực mạnh mẽ đến chuyển động của thị trường chứng khoán trong dài hạn, nhất là khi chính phủ không còn thực hiện lệnh đóng cửa. Kết quả nghiên cứu cho thấy không ghi nhận những hạn chế kéo dài của đại dịch COVID-19 đối với thị trường chứng khoán.
FAMILY PLANNING ATTITUDE IN TURKISH CULTURE: RELATIONSHIP BETWEEN EXPERIENCING UNINTENDED PREGNANCY, RECEIVING COUNSELING, AND ACCESSING METHODS
Authors: DURAN Büşra , DAĞ TÜZMEN Hafize , DÖNER Şerife İrem
Published: April 2023

Objective: In this study, it was aimed to determine the frequency of married women using methods related to family planning and the factors associated with method use.

Method: 400 women between the ages of 15 and 49 were a part of the research, which was carried out as a descriptive and relationship-seeking study. The family planning attitude scale and a personal information form were utilized in the data collection phase of the study, and data were analyzed using the IBM SPSS 25 program. Ethics committee permission and written consent from the participants were obtained for the habituation to take place. T-test, one-way variance, and multiple regression analyzes were used in the analysis of the data.

Results: It was determined that the total mean score of the family planning attitude scale of the women was 133.49 ± 18.78, 67% of them used a modern family planning method, and 32.5% of them received counseling for family planning. It has been found that women's family planning attitudes are affected by age, income level, availability of family planning products and method selection reasons. It has been determined that the family planning attitude scale sub-dimensions of women who have experienced abortion/abortion have lower attitudes towards family planning and family planning method attitudes than women who have not experienced abortion/abortion.

Conclusion: According to the research, women have positive attitudes regarding family planning, but not at the level that is ideal. More effectively delivering training and consulting services is crucial to fostering a good attitude toward family planning.
INVESTIGASI DAN PENILAIAN STRUKTUR BANGUNAN GEDUNG INDOMARET BASUKI RAHMAT KOTA SORONG
Authors: A. Didik S. Purwantoro  , Asriadi  , M. N. Fajar
Published: April 2023

Abstrak

Bangunan gedung adalah bentuk fisik hasil pekerjaan konstruksi yang dilaksanakan berdasarkan spesifikasi teknis, dan berfungsi sesuai peruntukannya. Struktur bangunan gedung terdiri dari stuktur atas yaitu portal diantaranya struktur balok (sloof/ring), struktur kolom berikut lantai, dan struktur bawah pondasi atau basement yang mendukung seluruh beban kerja struktur. Elemen-elemen struktur tersebut terintegrasi sebagai satu kesatuan dalam menyebarkan semua jenis beban ke tanah dasar (sub-grade). Kegagalan struktur adalah kondisi bangunan yang apabila ditinjau dari segi teknis tidak berfungsi secara keseluruhan, terjadi apabila tidak mengikuti standart perencanaan dan pelaksanaan, kesalahan input data preliminary design. Metode yang digunakan dalam penelitian ini adalah observasi dan Structural Analysis, Concrete Hammer Test (CHT), Dutch Cone Penetrometer Test (DCP-T). Hasil penelitian menunjukkan, mutu beton (fc’) struktur pelat lantai 100% tidak terpenuhi, struktur portal kolom dan struktur balok rata-rata 40.95% mutu beton (fc’) tidak terpenuhi, Soil-test diperoleh nilai conus resistance (qc) 5-10 kg/cm2 digolongkan jenis tanah lunak. Kapasitas dukung tanah dipakai nilai  = 44,73 kN/m2, tegangan tanah maksimum pada dasar fondasi = 234,844 kN/m,  > , tidak aman. Rekomendasinya antara lain pengurangan beban, titik-titik pondasi lebar foot-plat ditarik menjadi plat menerus mengikuti balok sloof, dan dilakukan improvement soil atau reinforced soil dengan consolidation grouting atau jet grouting.
Mortalidad materna en Colombia, 2019
Authors: Pinilla Saraza María Eugenia
Published: April 2023

Introducción: La vigilancia de la mortalidad materna es una herramienta para el monitoreo y toma de decisiones que pueden impactar en su reducción, su análisis es fundamental. Según datos de la OMS cada día mueren en todo el mundo cerca de 830 mujeres por complicaciones relacionadas con el embarazo o el parto, en Colombia según datos oficiales del Departamento Administrativo Nacional de Estadísticas (DANE) la razón de mortalidad materna presenta una tendencia decreciente pasando de 73,3 casos en el 2007 a 51,0 casos por 100 000 nacidos vivos en el 2017. En 2018 y 2019 se presentaron 46,1 y 47,1 / 100 000 nacidos vivos respectivamente. Objetivo: describir el comportamiento de la mortalidad materna durante el 2019, realizando un análisis con el año anterior y relacionando las principales variables socio-demográficas. Metodología: Se realizó un análisis descriptivo retrospectivo de los casos de mortalidad materna notificados al Sistema Nacional de Vigilancia en Salud Pública, donde se incluyó el análisis de las principales variables sociales, demográficas y del sistema de salud. Resultados: Durante el 2019 se notificaron 511 muertes maternas, de las cuales 298 se clasificaron como mortalidades maternas tempranas, se incluyeron 24 casos de nacionalidad extranjera ya que cumplen con la definición de residencia habitual. La tendencia de la razón de mortalidad materna durante los años 2009 a 2019 presento tendencia a la disminución la cual es estadísticamente significativa (P=0,000359). Se presentó aumento en las entidades territoriales de Vichada (p=0,0000), Guainía (p=0,000), Vaupés (p=0,0003), Atlántico (p=0,0070), Barranquilla (p=0,0065) y Cartagena (p=0,0276). La principal causa de muerte es la hemorragia obstétrica seguida del trastorno hipertensivo asociado al embarazo. Conclusiones: La mortalidad materna en Colombia durante los años 2009 a 2019 presenta una tendencia a la disminución; sin embargo, la región atlántica y amazónica muestran tendencia al aumento de casos.
Data-driven reduced order modeling for mechanical oscillators using Koopman approaches
Authors: Geier Charlotte , Stender Merten , Hoffmann Norbert
Published: April 2023

Data-driven reduced order modeling methods that aim at extracting physically meaningful governing equations directly from measurement data are facing a growing interest in recent years. The HAVOK-algorithm is a Koopman-based method that distills a forced, low-dimensional state-space model for a given dynamical system from a univariate measurement time series. This article studies the potential of HAVOK for application to mechanical oscillators by investigating which information of the underlying system can be extracted from the state-space model generated by HAVOK. Extensive parameter studies are performed to point out the strengths and pitfalls of the algorithm and ultimately yield recommendations for choosing tuning parameters. The application of the algorithm to real-world friction brake system measurements concludes this study.
Small extracellular vesicles derived from four dimensional-culture of mesenchymal stem cells induce alternatively activated macrophages by upregulating IGFBP2/EGFR to attenuate inflammation in the spinal cord injury of rats
Authors: Wang Junhua , Wei Qingshuai , Yang Yue , Che Mingtian , Ma Yuanhuan , Peng Lizhi , Yu Haiyang , Shi Huijuan , He Guanheng , Wu Rongjie , Zeng Ting , Zeng Xiang , Ma Wenbin
Published: April 2023

Effectively reducing the inflammatory response after spinal cord injury (SCI) is a challenging clinical problem and the subject of active investigation. This study employed a porous scaffold-based three dimensional long-term culture technique to obtain human umbilical cord mesenchymal stem cell (hUC-MSC)-derived Small Extracellular Vesicles (sEVs) (three dimensional culture over time, the “4D-sEVs”). Moreover, the vesicle size, number, and inner protein concentrations of the MSC 4D-sEVs contained altered protein profiles compared with those derived from 2D culture conditions. A proteomics analysis suggested broad changes, especially significant upregulation of Epidermal Growth Factors Receptor (EGFR) and Insulin-like Growth Factor Binding Protein 2 (IGFBP2) in 4D-sEVs compared with 2D-sEVs. The endocytosis of 4D-sEVs allowed for the binding of EGFR and IGFBP2, leading to downstream STAT3 phosphorylation and IL-10 secretion and effective induction of macrophages/microglia polarization from the pro-inflammatory M1 to anti-inflammatory M2 phenotype, both in vitro and in the injured areas of rats with compressive/contusive SCI. The reduction in neuroinflammation after 4D-sEVs delivery to the injury site epicenter led to significant neuroprotection, as evidenced by the number of surviving spinal neurons. Therefore, applying this novel 4D culture-derived Small Extracellular Vesicles could effectively curb the inflammatory response and increase tissue repair after SCI.
Surgical robot-assisted tripod percutaneous reconstruction technique combined with bone cement filling technique for the treatment of acetabular metastasis
Authors: Huang Zhen , Zhu Kun-Peng , Hu Jian-Ping , Zhu Yu-Run , Xu En-Jie , Ma Xiao-Long , Wang Yong-Jie , Zhang Chun-Lin
Published: April 2023

Background: Acetabular metastasis is a type of metastatic bone cancer, and it mainly metastasizes from cancers such as lung cancer, breast cancer, and renal carcinoma. Acetabular metastasis often causes severe pain, pathological fractures, and hypercalcemia which may seriously affect the quality of life of acetabular metastasis patients. Due to the characteristics of acetabular metastasis, there is no most suitable treatment to address it. Therefore, our study aimed to investigate a novel treatment technique to relieve these symptoms.

Methods: Our study explored a novel technique to reconstruct the stability of the acetabular structure. A surgical robot was used for accurate positioning and larger-bore cannulated screws were accurately inserted under the robot’s guidance. Then, the lesion was curetted and bone cement was injected through a screw channel to further strengthen the structure and kill tumor cells.

Results: A total of five acetabular metastasis patients received this novel treatment technique. The data relating to surgery were collected and analyzed. The results found that this novel technique can significantly reduce operation time, intraoperative bleeding, visual analogue score scores, Eastern Cooperative Oncology Group scores, and postoperative complications (e.g., infection, implant loosening, hip dislocation) after treatment. Follow-up time ranged from 3 months to 6 months, and the most recent follow-up results showed that all patients survived and no acetabular metastasis progressed in any of the patients after surgery.

Conclusion: Surgical robot-assisted tripod percutaneous reconstruction combined with the bone cement filling technique may be a novel and suitable treatment in acetabular metastasis patients. Our study may provide new insights into the treatment of acetabular metastasis.
Stalk-derived carbon dots as nanosensors for Fe3+ ions detection and biological cell imaging
Authors: Du Yongchao , Li Yaxi , Liu Yunliang , Liu Naiyun , Cheng Yuanyuan , Shi Qiuzhong , Liu Xiang , Tao Zhimin , Guo Yumeng , Zhang Jianguo , Askaria Najmeh , Li Haitao
Published: April 2023

Introduction: Iron is one of the most important needed elements for the growth and reproduction of living organisms. The detection of iron levels is important and developing fluorescent probes with excellent sensitivity for Fe3+ ions is of great significance. Carbon dot (CDs) is a new type of fluorescent nanomaterial based on abundant and low-cost carbon elements. The use of widely distributed renewable agricultural waste straw as a carbon precursor to prepare CDs sensor can not only reduce the pollution caused by burning straw to the atmospheric environment, but also achieve the transformation of resources from waste to treasure.

Methods: In this study, CDs were obtained from corn stalk powder by pyrolysis and microwave process. The sensitivity and linear response range of CDs sensor was studied through analyzing the effect of different Fe3+ ions concentrations on the fluorescence quenching. The application of CDs in biological cell imaging was investigated using HGC-27 cells.

Results: The fluorescence quenching showed a good linear relationship with the Fe3+ concentration in the range from 0 to 128 μM, and a low detection limit of 63 nM. In addition, the CDs have high recognition for Fe3+ ions. Meanwhile, the CDs have a low cytotoxicity and desirable biocompatibility, allowing the multicolor living cell imaging.

Conclusion: The prepared CDs can be used as fluorescent sensors for the selective detection of Fe3+ ions and biological cell imaging. Our results supported that the conversion of agricultural waste into carbon nanomaterials has great potential to be developed.
A census of actin-associated proteins in humans
Authors: Meenakshi S Iyer , Rao Madan , Mayor Satyajit , Sowdhamini Ramanathan
Published: April 2023

Actin filaments help in maintaining the cell structure and coordinating cellular movements and cargo transport within the cell. Actin participates in the interaction with several proteins and also with itself to form the helical filamentous actin (F-actin). Actin-binding proteins (ABPs) and actin-associated proteins (AAPs) coordinate the actin filament assembly and processing, regulate the flux between globular G-actin and F-actin in the cell, and help maintain the cellular structure and integrity. We have used protein–protein interaction data available through multiple sources (STRING, BioGRID, mentha, and a few others), functional annotation, and classical actin-binding domains to identify actin-binding and actin-associated proteins in the human proteome. Here, we report 2482 AAPs and present an analysis of their structural and sequential domains, functions, evolutionary conservation, cellular localization, abundance, and tissue-specific expression patterns. This analysis provides a base for the characterization of proteins involved in actin dynamics and turnover in the cell.
The learning potential of streaming media: cultural sustainability in a post-digital society
Authors: Heuman Johannes , Rampazzo Gambarato Renira
Published: April 2023

The aim of this article is to contribute to a discussion on the challenges of and opportunities for using major streaming media platforms and fictional streaming series in an educational context. The article departs from research on the post-digital condition, platformization, cultural memory, and cultural sustainability. The tangible interest in cultural memory and heritage studies indicates the current need to include streaming services in these research fields, as the platforms for streaming media are vectors of popular culture and heritage in terms of digital archives. With the help of Astrid Erll's analytical model, the authors argue that perspectives from cultural memory studies are useful for deepening the learning potential of fictional series on streaming platforms. The article also supports the idea that major streaming services can be used in education as a supplement to other cultural resources if the potential sustainability risks are considered.
Congenital aortic valve stenosis: from pathophysiology to molecular genetics and the need for novel therapeutics
Authors: Yasuhara Jun , Schultz Karlee , Bigelow Amee M. , Garg Vidu
Published: April 2023

Congenital aortic valve stenosis (AVS) is one of the most common valve anomalies and accounts for 3%–6% of cardiac malformations. As congenital AVS is often progressive, many patients, both children and adults, require transcatheter or surgical intervention throughout their lives. While the mechanisms of degenerative aortic valve disease in the adult population are partially described, the pathophysiology of adult AVS is different from congenital AVS in children as epigenetic and environmental risk factors play a significant role in manifestations of aortic valve disease in adults. Despite increased understanding of genetic basis of congenital aortic valve disease such as bicuspid aortic valve, the etiology and underlying mechanisms of congenital AVS in infants and children remain unknown. Herein, we review the pathophysiology of congenitally stenotic aortic valves and their natural history and disease course along with current management strategies. With the rapid expansion of knowledge of genetic origins of congenital heart defects, we also summarize the literature on the genetic contributors to congenital AVS. Further, this increased molecular understanding has led to the expansion of animal models with congenital aortic valve anomalies. Finally, we discuss the potential to develop novel therapeutics for congenital AVS that expand on integration of these molecular and genetic advances.
A modern day perspective on smoking in peripheral artery disease
Authors: Behrooz Leili , Abumoawad Abdelrhman , Rizvi Syed Husain M. , Hamburg Naomi M.
Published: April 2023

Peripheral artery disease (PAD) is associated with increased risk of cardiovascular morbidity and mortality, poor functional status, and lower quality of life. Cigarette smoking is a major preventable risk factor for PAD and is strongly associated with a higher risk of disease progression, worse post-procedural outcomes, and increased healthcare utilization. The arterial narrowing due to atherosclerotic lesions in PAD leads to decreased perfusion to the limbs and can ultimately cause arterial obstruction and limb ischemia. Endothelial cell dysfunction, oxidative stress, inflammation, and arterial stiffness are among the key events during the development of atherogenesis. In this review, we discuss the benefits of smoking cessation among patients with PAD and the use of smoking cessation methods including pharmacological treatment. Given that smoking cessation interventions remain underutilized, we highlight the importance of incorporating smoking cessation treatments as part of the medical management of patients with PAD. Regulatory approaches to reduce the uptake of tobacco product use and support smoking cessation have the potential to reduce the burden of PAD.
PD-1 limits differentiation and plasticity of Tc17 cells
Authors: Arra Aditya , Lingel Holger , Pierau Mandy , Brunner-Weinzierl Monika C.
Published: April 2023

Blockade of surface co-inhibitory receptor programmed cell death-1 (PD-1; CD279) has been established as an important immunotherapeutic approach to treat malignancies. On a cellular level, PD-1 is demonstrated to be of particular importance in inhibiting differentiation and effector function of cytotoxic Tc1 cells (CTLs). Nevertheless, the role of PD-1 in modulating interleukin (IL)-17-producing CD8+ T-cells (Tc17 cells), which generally display suppressed cytotoxic nature, is not well understood. To evaluate the impact of PD-1 in Tc17 responses, we examined its functioning using different in vitro and in vivo models. Upon activation of CD8+ T-cells in Tc17 environment, we found that PD-1 was rapidly expressed on the surface of CD8+ T-cells and triggered a T-cell-internal mechanism that inhibited the expression of IL-17 and Tc17-supporting transcription factors pSTAT3 and RORγt. Expression of type17-polarising cytokine IL-21 and the receptor for IL-23 were also suppressed. Intriguingly, adoptively transferred, PD-1-/- Tc17 cells were highly efficient in rejection of established B16 melanoma in vivo and displayed Tc1 like characteristics ex vivo. When using IL-17A-eGFP reporter mice for in vitro fate tracking, IL-17A-eGFP expressing cells lacking PD-1 signaling upon re-stimulation with IL-12 quickly acquired Tc1 characteristics such as IFN-γ, and granzyme B expression, implicating lineage independent upregulation of CTL-characteristics that are needed for tumor control. In line with plasticity characteristics, absence of PD-1 signaling in Tc17 cells increased the expression of the stemness and persistence-associated molecules TCF1 and BCL6. Thus, PD-1 plays a central role in the specific suppression of Tc17 differentiation and its plasticity in relation to CTL-driven tumor rejection, which provides further explanation as to why the blockade of PD-1 is such an efficient therapeutic target for inducing tumor rejection.
Host M-CSF induced gene expression drives changes in susceptible and resistant mice-derived BMdMs upon Leishmania major infection
Authors: Bouabid Cyrine , Rabhi Sameh , Thedinga Kristina , Barel Gal , Tnani Hedia , Rabhi Imen , Benkahla Alia , Herwig Ralf , Guizani-Tabbane Lamia
Published: April 2023

Leishmaniases are a group of diseases with different clinical manifestations. Macrophage-Leishmania interactions are central to the course of the infection. The outcome of the disease depends not only on the pathogenicity and virulence of the parasite, but also on the activation state, the genetic background, and the underlying complex interaction networks operative in the host macrophages. Mouse models, with mice strains having contrasting behavior in response to parasite infection, have been very helpful in exploring the mechanisms underlying differences in disease progression. We here analyzed previously generated dynamic transcriptome data obtained from Leishmania major (L. major) infected bone marrow derived macrophages (BMdMs) from resistant and susceptible mouse. We first identified differentially expressed genes (DEGs) between the M-CSF differentiated macrophages derived from the two hosts, and found a differential basal transcriptome profile independent of Leishmania infection. These host signatures, in which 75% of the genes are directly or indirectly related to the immune system, may account for the differences in the immune response to infection between the two strains. To gain further insights into the underlying biological processes induced by L. major infection driven by the M-CSF DEGs, we mapped the time-resolved expression profiles onto a large protein-protein interaction (PPI) network and performed network propagation to identify modules of interacting proteins that agglomerate infection response signals for each strain. This analysis revealed profound differences in the resulting responses networks related to immune signaling and metabolism that were validated by qRT-PCR time series experiments leading to plausible and provable hypotheses for the differences in disease pathophysiology. In summary, we demonstrate that the host’s gene expression background determines to a large degree its response to L. major infection, and that the gene expression analysis combined with network propagation is an effective approach to help identifying dynamically altered mouse strain-specific networks that hold mechanistic information about these contrasting responses to infection.
Improvement of cognitive function in wild-type and Alzheimer´s disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells
Authors: Casares Noelia , Alfaro María , Cuadrado-Tejedor Mar , Lasarte-Cia Aritz , Navarro Flor , Vivas Isabel , Espelosin María , Cartas-Cejudo Paz , Fernández-Irigoyen Joaquín , Santamaría Enrique , García-Osta Ana , Lasarte Juan José
Published: April 2023

A complex network of interactions exists between the olfactory, immune and central nervous systems. In this work we intend to investigate this connection through the use of an immunostimulatory odorant like menthol, analyzing its impact on the immune system and the cognitive capacity in healthy and Alzheimer’s Disease Mouse Models. We first found that repeated short exposures to menthol odor enhanced the immune response against ovalbumin immunization. Menthol inhalation also improved the cognitive capacity of immunocompetent mice but not in immunodeficient NSG mice, which exhibited very poor fear-conditioning. This improvement was associated with a downregulation of IL-1β and IL-6 mRNA in the brain´s prefrontal cortex, and it was impaired by anosmia induction with methimazole. Exposure to menthol for 6 months (1 week per month) prevented the cognitive impairment observed in the APP/PS1 mouse model of Alzheimer. Besides, this improvement was also observed by the depletion or inhibition of T regulatory cells. Treg depletion also improved the cognitive capacity of the APPNL-G-F/NL-G-F Alzheimer´s mouse model. In all cases, the improvement in learning capacity was associated with a downregulation of IL-1β mRNA. Blockade of the IL-1 receptor with anakinra resulted in a significant increase in cognitive capacity in healthy mice as well as in the APP/PS1 model of Alzheimer´s disease. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals, highlighting the potential of odors and immune modulators as therapeutic agents for CNS-related diseases.
Dietary α-ketoglutarate alleviates glycinin and β-conglycinin induced damage in the intestine of mirror carp (Cyprinus carpio)
Authors: Luo Qiaohua , Qian Rendong , Qiu Zongsheng , Yamamoto Fernando Y. , Du Yingying , Lin Xiaowen , Zhao Jianhua , Xu Qiyou
Published: April 2023

This study investigated the glycinin and β-conglycinin induced intestinal damage and α-ketoglutarate alleviating the damage of glycinin and β-conglycinin in intestine. Carp were randomly divided into six dietary groups: containing fish meal (FM) as the protein source, soybean meal (SM), glycinin (FMG), β-conglycinin (FMc), glycinin+1.0% α-ketoglutarate (AKG) (FMGA), β-conglycinin+1.0% AKG (FMcA). The intestines were collected on 7th, and the hepatopancreas and intestines were collected on 56th. Fish treated with SM and FMc displayed reduced weight gain, specific growth rate, and protein efficiency. On 56th day, Fish fed on SM, FMG and FMc presented lower superoxide dismutase (SOD) activities. FMGA and FMcA had higher SOD activity than those fed on the FMG and FMc, respectively. In intestine, fish fed on the SM diets collected on 7th presented upregulated the expression of transforming growth factor beta (TGFβ1), AMP-activated protein kinase beta (AMPKβ), AMPKγ, and acetyl-CoA carboxylase (ACC). Fish fed FMG presented upregulated expression of tumor necrosis factor alpha (TNF-α), caspase9, and AMPKγ, while downregulated the expression of claudin7 and AMPKα. FMc group presented upregulated expression of TGFβ1, caspase3, caspase8, and ACC. Fish fed FMGA showed upregulated expression of TGFβ1, claudin3c, claudin7, while downregulating the expression of TNF-α and AMPKγ when compared to fish fed FMG diet. FMcA upregulated the expression of TGFβ1, claudin3c than fed on the FMc. In intestine, the villus height and mucosal thickness of the proximal intestine (PI) and the distal intestine (DI) were decreased and crypt depth of the PI and mid intestine (MI) were increased in SM, FMG and FMc. In addition, fish fed on SM, FMG and FMc presented lower citrate synthase (CS), isocitrate dehydrogenase (ICD), α-ketoglutarate dehydrogenase complex (α-KGDHC) Na+/K+-ATPase activity in DI. FMGA had higher CS, ICD, α-KGDHC, and Na+/K+-ATPase activity in PI and MI than those fed on the FMG. FMcA had higher Na+/K+-ATPase activity in MI. In conclusion, dietary soybean meal destroys the intestine’s health, the adverse effects are related to the presence of β-conglycinin and glycinin, especially glycinin. AKG may regulate intestinal energy via tricarboxylic acid cycle, thereby alleviating the damage intestinal morphology caused by the dietary soybean antigen proteins.
A predictive model for identifying secondary underlying diseases of hemophagocytic lymphohistiocytosis
Authors: Gao Wei-bo , Hu Li-juan , Ma Xiao-lu , Shi Mao-jing , Wang Chun-yu , Ma Yong , Song Xiao-jing , Zhu Ji-hong , Wang Tian-bing
Published: April 2023

Background

Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation that arises in the context of infectious, inflammatory, or neoplastic triggers. The aim of this study was to establish a predictive model for the timely differential diagnosis of the original disease resulting in HLH by validating clinical and laboratory findings to further improve the efficacy of therapeutics for HLH.

Methods

We retrospectively enrolled 175 secondary HLH patients in this study, including 92 patients with hematologic disease and 83 patients with rheumatic disease. The medical records of all identified patients were retrospectively reviewed and used to generate the predictive model. We also developed an early risk score using multivariate analysis weighted points proportional to the β regression coefficient values and calculated its sensitivity and specificity for the diagnosis of the original disease resulting in HLH.

Results

The multivariate logistic analysis revealed that lower levels of hemoglobin and platelets (PLT), lower levels of ferritin, splenomegaly and Epstein−Barr virus (EBV) positivity were associated with hematologic disease, but young age and female sex were associated with rheumatic disease. The risk factors for HLH secondary to rheumatic diseases were female sex [OR 4.434 (95% CI, 1.889-10.407), P =0.001], younger age [OR 6.773 (95% CI, 2.706-16.952), P<0.001], higher PLT level [OR 6.674 (95% CI, 2.838-15.694), P<0.001], higher ferritin level [OR 5.269 (95% CI, 1.995-13.920), P =0.001], and EBV negativity [OR 27.656 (95% CI, 4.499-169.996), P<0.001]. The risk score included assessments of female sex, age, PLT count, ferritin level and EBV negativity, which can be used to predict HLH secondary to rheumatic diseases with an AUC of 0.844 (95% CI, 0.836~0.932).

Conclusion

The established predictive model was designed to help clinicians diagnose the original disease resulting in secondary HLH during routine practice, which might be improve prognosis by enabling the timely treatment of the underlying disease.
Changes in HCMV immune cell frequency and phenotype are associated with chronic lung allograft dysfunction
Authors: Rousselière Amélie , Delbos Laurence , Foureau Aurore , Reynaud-Gaubert Martine , Roux Antoine , Demant Xavier , Le Pavec Jérôme , Kessler Romain , Mornex Jean-François , Messika Jonathan , Falque Loïc , Le Borgne Aurélie , Boussaud Véronique , Tissot Adrien , Hombourger Sophie , Bressollette-Bodin Céline , Charreau Béatrice
Published: April 2023

Background

Human cytomegalovirus (HCMV) infection is common and often severe in lung transplant recipients (LTRs), and it is a risk factor associated with chronic lung allograft dysfunction (CLAD). The complex interplay between HCMV and allograft rejection is still unclear. Currently, no treatment is available to reverse CLAD after diagnosis, and the identification of reliable biomarkers that can predict the early development of CLAD is needed. This study investigated the HCMV immunity in LTRs who will develop CLAD.

Methods

This study quantified and phenotyped conventional (HLA-A2pp65) and HLA-E-restricted (HLA-EUL40) anti-HCMV CD8+ T (CD8 T) cell responses induced by infection in LTRs developing CLAD or maintaining a stable allograft. The homeostasis of immune subsets (B, CD4T, CD8 T, NK, and γδT cells) post-primary infection associated with CLAD was also investigated.

Results

At M18 post-transplantation, HLA-EUL40 CD8 T responses were less frequently found in HCMV+ LTRs (21.7%) developing CLAD (CLAD) than in LTRs (55%) keeping a functional graft (STABLE). In contrast, HLA-A2pp65 CD8 T was equally detected in 45% of STABLE and 47.8% of CLAD LTRs. The frequency of HLA-EUL40 and HLA-A2pp65 CD8 T among blood CD8 T cells shows lower median values in CLAD LTRs. Immunophenotype reveals an altered expression profile for HLA-EUL40 CD8 T in CLAD patients with a decreased expression for CD56 and the acquisition of PD-1. In STABLE LTRs, HCMV primary infection causes a decrease in B cells and inflation of CD8 T, CD57+/NKG2C+ NK, and δ2−γδT cells. In CLAD LTRs, the regulation of B, total CD8 T, and δ2+γδT cells is maintained, but total NK, CD57+/NKG2C+ NK, and δ2−γδT subsets are markedly reduced, while CD57 is overexpressed across T lymphocytes.

Conclusions

CLAD is associated with significant changes in anti-HCMV immune cell responses. Our findings propose that the presence of dysfunctional HCMV-specific HLA-E-restricted CD8 T cells together with post-infection changes in the immune cell distribution affecting NK and γδT cells defines an early immune signature for CLAD in HCMV+ LTRs. Such a signature may be of interest for the monitoring of LTRs and may allow an early stratification of LTRs at risk of CLAD.
PR1P, a VEGF-stabilizing peptide, reduces injury and inflammation in acute lung injury and ulcerative colitis animal models
Authors: Adini Avner , Ko Victoria H. , Puder Mark , Louie Sharon M. , Kim Carla F. , Baron Joseph , Matthews Benjamin D.
Published: April 2023

Acute Respiratory Distress Syndrome (ARDS) and Ulcerative Colitis (UC) are each characterized by tissue damage and uncontrolled inflammation. Neutrophils and other inflammatory cells play a primary role in disease progression by acutely responding to direct and indirect insults to tissue injury and by promoting inflammation through secretion of inflammatory cytokines and proteases. Vascular Endothelial Growth Factor (VEGF) is a ubiquitous signaling molecule that plays a key role in maintaining and promoting cell and tissue health, and is dysregulated in both ARDS and UC. Recent evidence suggests a role for VEGF in mediating inflammation, however, the molecular mechanism by which this occurs is not well understood. We recently showed that PR1P, a 12-amino acid peptide that binds to and upregulates VEGF, stabilizes VEGF from degradation by inflammatory proteases such as elastase and plasmin thereby limiting the production of VEGF degradation products (fragmented VEGF (fVEGF)). Here we show that fVEGF is a neutrophil chemoattractant in vitro and that PR1P can be used to reduce neutrophil migration in vitro by preventing the production of fVEGF during VEGF proteolysis. In addition, inhaled PR1P reduced neutrophil migration into airways following injury in three separate murine acute lung injury models including from lipopolysaccharide (LPS), bleomycin and acid. Reduced presence of neutrophils in the airways was associated with decreased pro-inflammatory cytokines (including TNF-α, IL-1β, IL-6) and Myeloperoxidase (MPO) in broncho-alveolar lavage fluid (BALF). Finally, PR1P prevented weight loss and tissue injury and reduced plasma levels of key inflammatory cytokines IL-1β and IL-6 in a rat TNBS-induced colitis model. Taken together, our data demonstrate that VEGF and fVEGF may each play separate and pivotal roles in mediating inflammation in ARDS and UC, and that PR1P, by preventing proteolytic degradation of VEGF and the production of fVEGF may represent a novel therapeutic approach to preserve VEGF signaling and inhibit inflammation in acute and chronic inflammatory diseases.
The roles of ERIANIN in tumor and innate immunity and its’ perspectives in immunotherapy
Authors: Yang Zhen , Liu Ruxue , Qiu Minghan , Mei Hanwei , Hao Jie , Song Teng , Zhao Ke , Zou Dandan , Wang Huaqing , Gao Ming
Published: April 2023

Traditional Chinese medicine has been used in China for thousands of years. In 2022, the 14th Five-Year Plan for the Development of Traditional Chinese Medicine was released, aiming to enhance traditional Chinese medicine health services and improve policies and systems for high-quality traditional Chinese medicinal development by 2025. ERIANIN, the main component of the traditional Chinese medicine Dendrobium, plays an important role in anti-inflammatory, antiviral, antitumor, antiangiogenic, and other pharmacological effects. ERIANIN has broad-spectrum antitumor effects, and its tumor-suppressive effects have been confirmed in the study of various diseases, such as precancerous lesions of the stomach, gastric cancer, liver cancer, lung cancer, prostate cancer, bladder cancer, breast cancer, cervical cancer, osteosarcoma, colorectal cancer, leukaemia, nasopharyngeal cancer and melanoma through the multiple signaling pathways. Thus, the aim of this review was to systematically summarise the research on ERIANIN with the aim of serving as a reference for future research on this compound and briefly discuss some future perspectives development of ERIANIN in combined immunotherapy.