bluuebunny/crossref_metadata_2025 huggingface dataset:
Investment climate of countries in conditions of financial instability
Authors: Yarovenko Tetiana , Berezhna Sofiia
Published: September 2023

The article points out that financial crises are especially dangerous for the investment climate of developing countries or countries with transitional economies. It considers approaches to the interpretation of the concept of «investment climate of a country» and its features. Based on that, the author's own interpretation of this concept is presented as a complex of political, legal, financial, economic, social, institutional, innovative, infrastructural and other conditions of investment activity of recipients and other subjects of the investment system, which affect the investment process, facilitating or impeding it with a purpose of attracting investments into a certain country. It is determined that the main cause of financial instability in recent years has been the Covid-19 pandemic, which has led to a decrease in investment activity, insufficient liquidity of investments and a decline in their attractiveness in many sectors, and a deterioration in the investment climate in the world. It is noted that global financial instability has a negative impact on the countries' investment climate, which is reflected in: a decrease in investor trust in investment objects; increased riskiness of investments; and rising costs of attracting foreign investment to the country. The author analyses changes in the total volume of investments in the world for the period 1990–2021, which indicates a more favourable investment climate in economically developed countries, but it is more affected by financial instability compared to developing countries. It is established that in order to ensure a favourable investment climate in Ukraine, the legislative framework provides guarantees for investors' activities, opportunities for public-private investment partnerships, etc. The author identifies the shortcomings that make the investment climate in Ukraine unfavourable. The list of measures to improve the investment climate of world countries in the context of financial instability is substantiated. It is noted that ensuring an attractive investment climate in the country in crisis conditions is possible only through a targeted investment strategy and a specific system of measures that will provide conditions for economic recovery after the recession.
Formation of a competitive profile of domestic companies in the global business environment
Authors: Skrypnyk Nataliia , Zakharchenko Bohdan
Published: September 2023

The article examines the key aspects of the process of Ukrainian companies entering the global market: prerequisites and factors influencing the international development of companies during expansion and establishment in the context of modern competitive relations; forms of business and enterprise development. A brief structural analysis of the main development strategies of companies in the conditions of entering the markets of other countries is carried out, examples of the strategies of international development of large domestic companies, international cooperation and the construction of successful enterprises are given. The main trends of the entry of domestic companies into the international business environment are highlighted and the features of competitive opportunities of Ukrainian enterprises are revealed, the problems of competitiveness of Ukrainian companies in the international business arena are analyzed. It is analyzed how global economic processes affect the international division of production factors and the territorial location of productive forces. International competition, globalization of markets, large-scale penetration of foreign goods into the Ukrainian market transfer the problem of managing the competitiveness of the enterprise to the number of priority management tasks, the successful solution of which will ensure the survival and development of enterprises in the new environment. The globalization of the world economy opens up unprecedented opportunities for the development of international business, the characteristic features of which are: accessibility and generality, gradual development, the possibility of carrying out activities in real time, covering all markets of goods and services with the help of telecommunications. The importance and value of business for the world economy is determined by maintaining a competitive market environment, which is a key function at all stages of the development of the world economy. Modern competition is the competition of new companies in terms of strategy, production organization and business culture. The key factors of the successful development of domestic and international companies, such as investment attraction, the use of scientific and innovative developments, and the use of organizational and management experience, were studied.
Improvement of mechanisms of formation and implementation the state export policy in Ukraine
Authors: Zhabynets Olha
Published: September 2023

It was assessment the prospects for the application of an export-oriented growth strategy in Ukraine as the basis of the economic growth strategy based on the analysis of foreign practices and achieved economic results. It has been established that the effectiveness of the implementation of the export-oriented growth strategy in our country will be successful only with the active introduction of innovative technologies in the production of goods and services due to the inflow of direct foreign investments in export-oriented sectors of the economy. The draft plan of measures for the post-war recovery and development of Ukraine was analyzed. A number of measures necessary for the implementation of the export-oriented growth strategy were identified. The institutional, financial and resource support of export activity are analyzed. It has been established that the existing network of trade support institutions in Ukraine is not able to fully ensure the proper level of effective support for Ukrainian exporters on international markets. Furthermore, the mechanism of interaction and cooperation of state export support institutions, in particular the International Trade Council under the Cabinet of Ministers of Ukraine, with other institutions in the field of international trade and enterprises of the real sector of the economy is imperfect. It was noted that the realization of export entrepreneurial potential in Ukraine is held back today not only by global factors (pandemic, war etc.), but also by internal obstacles, among which, in particular, the absence of a strategic document in the export activity of the state - the Export Strategy of Ukraine, which would cover the main principles of export policy implementation during the war and during the post-war recovery period. It has been argued the necessity to updating and actualization the Export Strategy of Ukraine, which will determine the main directions of development of Ukraine's international trade and support of export-oriented enterprises, especially small and medium-sized businesses, taking into account new challenges and prospects. It was noted that state and non-state, including with the participation of international organizations, financial and non-financial support of export activities are important tools for financial and resource support of domestic exports today. It has been argued the necessity of introducing a mechanism of insurance of investments of domestic and foreign investors against military risks in Ukraine. Measures to increase the effectiveness of the consultative and advisory activities of the International Trade Council and the financial capacity of domestic exporters, including with the participation of the Export Credit Agency, was proposed.
Pensar la enseñanza en el Antropoceno. Implicancias de un sustento filosófico posible
Authors: Hereñú Adriana
Published: September 2023

Este trabajo es un intento por pensar la enseñanza en este tiempo denominado Antropoceno que reclama nuevos posicionamientos desde lo pedagógico, filosófico y político. Una breve descripción del momento actual de la humanidad nos ubica en una realidad donde es urgente otra relación con la naturaleza en el marco de la creciente digitalización. Esto implica necesariamente interpelar el capitalismo en su fase neoliberal de depredación de los recursos naturales y desigualdades que se profundizan cada vez más. Para sustentar el posicionamiento se propone un encuadre filosófico desde el cual pensar una política curricular posible para encarar este desafío, tomando como base algunos conceptos de Spinoza. También se plantea un abordaje curricular situado en las instituciones como ámbito capaz de producir conocimientos y de diseñar propuestas de enseñanzas situadas. Como educadores tenemos la tarea ineludible de considerar las nuevas problemáticas que se han ido configurando en estos últimos años para comprometernos con una discusión teórica urgente y a su vez para accionar diseñando y poniendo en práctica propuestas de enseñanza que las aborden desde distintas perspectivas y áreas de saber.
padres opinan sobre la formación. La voz del imaginario colectivo
Authors: Angulo Villanueva Rita Guadalupe , Moreno Martínez Nehemías , Pérez García Edgar Alfonso
Published: September 2023

Sobre el supuesto de que está surgiendo en el imaginario social un ideal formativo distinto (código curricular emergente) para las nuevas generaciones, nos preguntamos sí ¿los curricula deben ser modificados? Nuestro propósito es buscar el imaginario sobre la formación de las nuevas generaciones. Realizamos una investigación cualitativa mediante estudio de casos e interpretación por teoría fundamentada. Hemos seleccionado como población objetivo a los profesionistas, los estudiantes universitarios, los trabajadores en oficios diversos y los maestros, todos ellos padres de familia. En este texto presentamos el segundo sondeo que hemos levantado solamente con padres de familia; en sondeos posteriores se levantarán datos con los otros grupos poblacionales. Este sondeo se apoya en la categorización teórica elaborada previamente (Angulo, 2022) y el primer acercamiento mediante entrevistas a profundidad (Angulo, Moreno y Aguiñaga, 2022). En está ocasión, se aplicó un cuestionario con respuestas cerradas a 28 personas y una sola pregunta de respuesta abierta; se organizó en cuatro secciones (1ª correo, 2ª datos generales, 3ª rasgos de la formación, 4ª cuidarse a sí mismo, a los demás y convivir).  La última sección fue identificada en el primer acercamiento como el rasgo formativo más importante para los informantes entrevistados. En este levantamiento vuelve a mostrarse como el rasgo formativo esencial para los padres encuestados. Los resultados muestran que los curricula escolares, incluidos los universitarios, requieren ser reformulados a fin de brindar una formación integral que, si bien se ofrece en el nivel educativo de preescolar paulatinamente se difumina en favor de una formación más disciplinar y sin que este tipo de formación deje de ofrecerse, el rasgo formativo fundamental habrá de ser la formación para la vida, el cuidado de sí y el aprendizaje para vivir y convivir. Aparece también, el interés por contenidos útiles en la cotidineidad y que la escuela no ofrece.
Del texto escrito al presente postpandemia: nada volverá a ser como antes
Authors: Alderete Alicia
Published: September 2023

La pandemia de COVID-19 modificó las estructuras de las relaciones económicas, sociales, culturales, educativas; por mencionar solo algunas de las estructuras que organizan la vida cotidiana de las personas. Resulta clave el segmento temporal comprendido entre los años 2020-2022 al momento de construir y producir textos, saberes, discursos en torno al currículum, la didáctica, la enseñanza en este contexto pospandemia. Es (casi) irrefutable concebir a este fenómeno como una irrupción que se dio en todos los ámbitos y se coló por cada quebradura que se abría a su paso. Nada volverá a ser como antes es un imperativo que circula en este presente al que reconocemos como pospandemia. Advertir algunos pasajes que se dan del texto escrito (curricular) a las circunstancias institucionales educativas del presente nos permite percibir algunos desafíos actuales y evocar algunas orientaciones sobre lecturas y miradas en esta contingencia.
La pandemia, como rasgo disruptivo dislocante, y a posteriori los efectos pospandemia, están planteando un escenario en el que se dan por acabadas las instituciones del Estado. Esta vacuidad del significante por parte de los discursos hegemónicos es una preocupación, pues remite al acabose de la escuela como institución pública que articula lo común y en ello, al currículum como texto que representa lo común. Retomar el significante pospandemia y otorgarle sentidos incesantemente, reconocer las tramas discursivas y los juegos del lenguaje que lo constituyen en cada escenario particular donde dejó su rastro, ayudará a leer mejor las circunstancias del presente. Traducir el texto curricular en los escenarios educativos escolares de pospandemia exige dar sentidos políticos, identitarios, locales, internacionales a los discursos curriculares que allí se traman.
AFTER ACTION REVIEW AS A PART OF THE EDUCATIONAL PROCESS IN MILITARY EDUCATIONAL INSTITUTIONS
Authors:   National Academy of the National Guard of Ukraine, Mynko О. , Morozov I. ,   National Academy of the National Guard of Ukraine
Published: September 2023

The requirements of the governing documents regarding the organization of the analysis of the conducted actions ‒ After action Review, as a part of the internal communication work in the educational process and during the preparation and conduct of combat operations (conducting special operations) were analyzed. The experience of NATO member countries in implementing of the After Action Review conducted in the process of training and training of troops is considered. The relevance of the After Action Review and its role and place in the Lessons Learned System at the current stage of development of the security and defense forces of Ukraine are emphasized. The existing methodology for the implementation of the After Action Review in the training process and during the preparation and conduct of combat operations (conducting special operations) was analyzed. Prospects for the mandatory implementation of the process of studying the After Action Review methodology in military educational institutions and the expected effect were considered. It is expected that this will significantly contribute to the formation of commanders' growth mindset, which will transform consciousness and significantly improve the understanding of conclusions from the acquired training and combat experience. It will also allow to finally get rid of the fixed mindset that blocks any positive changes. In view of the ongoing Russian-Ukrainian war, the need for accelerated implementation of NATO standards ‒ the security and defense forces of Ukraine must undergo a process of important changes in the field of After Action Review process, Lessons Learned and exchange of combat experience as soon as possible.
ORGANIZATIONAL AND LEGAL PRINCIPLES OF COMBATING EXTREMISM AND WAYS OF IMPROVEMENT
Authors:   National University of Defense of Ukraine, Haman I.
Published: September 2023

The article examines the meaning of the concept of "extremism", reveals its illegal essence, signs and causes of its occurrence, and also outlines the lack of a legal definition of the concept of "extremism" in the legislation of Ukraine. The author emphasizes the organizational and legal principles of combating extremism and substantiates the opinion that the main source of extremism is the crisis state of society. A description of the types of extremism and its main forms and consequences for society is given. Thus, among the main forms of extremism we distinguish: production, storage or distribution of extremist materials (inscriptions, leaflets, audiovisual and other materials), use of Internet resources for extremist activities; public statements of extremist content; public appeals or incitement to commit extremist actsfinancing of extremist actions or other assistance in their organization, preparation and implementation, including by providing financial funds, real estate, educational, printing and material-technical base, telephone, fax and other types of communication, as well as providing information services. Derivatives of extremism are singled out, in particular: terrorism, collaborationism, separatism. The characteristics of subjects fighting extremism are presented separately (state authorities and local self-government bodies that participate within their competence; the Security Service of Ukraine and the State Bureau of Investigation, if representatives of authorities participate in extremist activities), as well as the content of the main directions of combating it. Prospective directions for further scientific research are the study of the experience of the countries of the European Union in countering extremism, the current state of countering extremism in Ukraine, and ways to improve the domestic legislation.
THE IMAGE OF AN EFFECTIVE SERGEANT OF THE NATIONAL GUARD OF UKRAINE
Authors:   National Academy of the National Guard of Ukraine, Matsegora Ya. , Kolesnychenko O. ,   National Academy of the National Guard of Ukraine, Batsamut V. ,   National Academy of the National Guard of Ukraine, Leshchenko S. ,   National Guard of Ukraine
Published: September 2023

The role of sergeants in military units is difficult to overestimate. Quite often, sergeants are more experienced than their immediate commanders ‒ junior officers. The reform of the sergeant's staff contributed to the formation in the minds of servicemen of the image of a sergeant as close as possible to the requirements of NATO, intensive participation in military operations and their provision put forward the requirements for the sergeant's reliability ‒ his ability to perform the task under any conditions, his loyalty to his comrades in arms ‒ to the leading positions and the Motherland. However, servicemen who perform tasks in the zone of direct combat conflict rate more highly the necessary characteristics of a sergeant, which ensure effective teamwork. In support units, sergeants are expected to have the most human-centered approach to personnel. The results of the study of the perception of the image of an effective sergeant in combat units and support units of the National Guard of Ukraine are presented. Reasoned groups of characteristics that determine the effectiveness of sergeants, as assessed by servicemen with intensive combat experience and rear support experience. It is proved that the structure of the characteristics of the sergeants of combat units and rear support units of the National Guard of Ukraine has similar features that allow us to describe them as effective managers who are able to organize the work of the unit and achieve the set goals in the existing circumstances, taking into account the characteristics of each of their subordinates and the available resources for their motivation. However, it is expected from the sergeants of combat units that they will be able to activate, so to speak, the "zone of immediate development", contribute to raising the level of training of subordinates to a qualitatively new level, and as motivation they will use not only personal needs, but also stimulators belonging to to semantic regulation, go beyond the boundaries of an individual personality.
Dynamics and Stability of $\Xi$-Hilfer Fractional Fuzzy Differential Equations with Impulses
Authors: VIVEK Ravichandran , K. Kangarajan , VİVEK Dvivek , ELSAYED Elsayed
Published: September 2023

This paper deals with the existence, uniqueness, and Ulam-stability outcomes for $\Xi$-Hilfer fractional fuzzy differential equations with impulse. Further, by using the techniques of nonlinear functional analysis, we study the Ulam-Hyers-Rassias stability.
B-cell small lymphocytic lymphoma in a free-ranging South American fur seal (Arctocephalus australis)
Authors: de Amorim DB , Ribeiro PR , Bandinelli MB , Echenique JVZ , Bianchi MV , Almeida PR , Spilki FR , Baumbach LF , Sonne L
Published: September 2023

Lymphomas are malignant neoplasms of the hematopoietic system arising from lymphocytes with highly variable biologic behavior. B-cell small lymphocytic lymphoma (B-SLL) is a non-Hodgkin lymphoma infrequently described in domestic and wild animals. The present study describes a case of B-SLL in a free-ranging adult male Arctocephalus australis in Brazil. The main necropsy findings included poor body condition, generalized lymphadenomegaly, severe and diffuse splenomegaly, and multiple, white to yellow nodules in the kidneys and small intestine. Histologically, these organs were partially or totally effaced by neoplastic small lymphocytes arranged in sheets, with moderate anisocytosis and anisokaryosis and a low mitotic count. These cells diffusely immunolabeled for CD79α and CD20, and were negative for CD3. A diagnosis of multicentric B-SLL was established and to the authors’ knowledge, it has not been previously described in this genus.
Marine heatwaves affect breeding, diet and population size but not body condition of a range-edge little penguin colony
Authors: Cannell BL , Kendall WL , Tyne JA , Bunce M , Hetzel Y , Murray D , Radford B
Published: September 2023

Significant marine heatwaves (MHWs) developed along the Western Australian coast in 1999 and 2011. Despite ecosystem losses and the southwards occurrence of many tropical fish species during and after the extreme MHW in 2011, there have been few studies on the effects of this MHW on seabirds, and no biological impacts related to the 1999 MHW have been reported. Using data from 1986-2019, we investigated the impacts of these events on breeding outcomes, body condition, diet composition, population size and mortality of little penguins on Penguin Island, in the temperate waters off Western Australia. Breeding outcomes were negatively impacted by the MHWs but body condition was not. Diet composition changed after the MHW, with sandy sprat Hyperlophus vittatus, the penguins’ typical major prey component, replaced by scaly mackerel Sardinella lemuru, a tropical fish species. Using an open robust design analysis that accounts for imperfect capture probabilities and staggered annual arrival and departure dates, we found that the population decreased by 80% following the 2011 MHW. Finally, more penguins died from starvation or from novel protozoal parasitic infections in 2011 and 2012 that were potentially introduced with the changed diet. This research highlights that the temporal and spatial influence of MHWs on seabirds depends on several factors. Furthermore, the magnitude and direction of a prey species’ response can be very localised and have significant impacts on avian predators. There are no obvious ways to mediate climate effects, but perhaps measures taken to reduce any synergistic impacts on prey abundance, particularly during MHW events, could be effective.
Resiliensi Matematis Siswa SMP pada Pembelajaran Matematika Secara Daring
Authors: Nuraini Aisyah , Hakim Dori Lukman
Published: September 2023

Sikap positif dalam pembelajaran matematika adalah bagian yang begitu penting dan harus ada dalam diri siswa karena dapat mengurangi hambatan yang dihadapi saat pembelajaran berlangsung. Wabah covid-19 telah merubah semua bidang, termasuk aspek pendidikan. Guru maupun siswa dituntut untuk melakukan pembelajaran secara daring, hal ini tentunya berpengaruh terhadap resiliensi matematis siswa. Oleh karena itu, artikel ini mempunyai tujuan untuk mendeskripsikan resiliensi matematis siswa SMP pada pembelajaran matematika secara daring. Penggunaan metode dalam artikel ini adalah deskriptif kualitatif dengan instrumen yang digunakan adalah instrumen non tes berupa angket berjumlah 30 butir pernyataan yang dapat ditanggapi oleh siswa melalui skala likert dengan rentang poin 1 sampai 5. Subjek yang diambil merupakan siswa kelas IX pada salah satu SMP di Kabupaten Karawang. Dari hasil analisis yang telah dilakukan, siswa masih mampu mengatasi kendala-kendala teknis saat pembelajaran berlangsung. Namun kendala siswa terletak pada tingkat pemahaman dan  kurangnya inovasi guru dalam penyampaian materi yang hanya berpaku pada buku saja sehingga perlu adanya pengembangan baik dari segi model pembelajaran maupun bentuk materi yang disampaikan.
Ecological risks of pesticide pollution of beekeeping products
Authors: Lishchuk A. , Horodyska І. , Karachinska N.
Published: September 2023

The article is focused on the actuality of the ecological risks researching of pesticide pollution of agricultural soils, which are the feed and raw material base for beekeeping. There is mentioned the importance of permanent control over the content of dangerous toxicants, in particular chlororganic pesticides, in the bee honey and other beekeeping products in the article. The results of researching the content of residual amounts of persistent chlororganic pesticides hexachlorocyclohexane (HCH) and dichlorodiphenyltrichlormethylmethane (DDT) in samples of the sunflower honey which are taken from the bee farm of three administrative districts of Cherkasy region are presented. Significant pollution of the sunflower honey from the bee farm which is placed in the village of Novoselytsia by residual amounts of pesticides is detected, the concentration of the sum of metabolites and isomers DDT exceeding the maximum allowable standards in 1.3 to 2.3 times. It should be noted that the determined concentrations of the above mentioned pesticide in the soil (from 6.41 to 23.53 mcg/kg for the MRL is equal 100 mcg/kg) cannot be a source of significant pollution of bee honey. It is suggested that the reason for the xenobiotic entering to bee products through the biological cycle (soil – honey plant – honey) is the presence in the range of honey collection area of anonactive compound of toxic chemicals, which is a powerful source of toxicants, including pesticides into environmental objects. It is detected the direct correlation dependance between the content of pesticides in honey and their concentration in the soil (in the range from r=0.61 for the village of Stebne to r=0.98 for villages of Novoselytsia and Chervone). The importance of assessment of ecological risks of environmental pollution by pesticide residues was proved, since even a small concentration of a toxic substance in soil, water, air, nectar or pollen of honey plants often leads to massive damage and death of bees. It is noted that honey can be used as a suitable bioindicator for assessing the ecological risks of environmental pollution by toxic substances, including chlororganic pesticides.
Influence of Vympel 2 and Oracul multicomplex biopreparations and their mixture on spring barley (Hordeum L.) plants of different varieties
Authors: Mosiychuk I. , Havryliuk L. , Beznosko I. , Turovnik Yu
Published: September 2023

The study of mechanisms of biological preparations influence on the plants of agricultural crops in order to improve and regulate their growth is an urgent task in agroecology. So, the article presents the results of studies of changes in biometric parameters of spring barley plants depending on the effect of biological preparations Vympel 2, Oracle multicomplex and their mixture (Vympel 2 + Oracle multicomplex). The research was conducted on the basis of temporary field experiments (Skvyra research station of organic production of IAEM of the National Academy of Sciences) and at the department of agrobioresources and ecologically safe technologies in the laboratory of biocontrol of agroecosystems and organic production of the IAEM of the National Academy of Sciences. In the course of the work, it was determined that under the influence of the mixture of Vympel 2 + Oracul multicomplex preparations, spring barley plants of varieties Sebastian and Helios, in the phase of full grain maturity, were 10 cm taller compared to the option without treatment (control). This shows that the treatment of spring barley plants with microfertilizer and growth stimulator ensured an increase in the linear dimensions of plants in height in all phases of their development. It has been established that the influence of preparations Vympel 2, Oracul multicomplex and their mixture (Vympel 2 + Oracul multicomplex) enhances the formation of the assimilation apparatus, which improves the conditions for the growth and development of spring barley plants, both due to the stimulating properties of the plant growth regulator and the improvement of soil nutrition conditions from the side of microfertilizer, which affects the formation of high-yielding crops. It was analyzed that the ear length, the number of grains in the ear, and the mass of grains of spring barley plants changed under the influence of the preparations, which depends on the varietal characteristics of the plants and the stimulating effect of the studied preparations. The best results were obtained by using the Vympel 2 + Oracul multicomplex mixture on plants of the Sebastian variety, where the length of the ear was 2 cm higher, and the weight of the grains was 22 g heavier compared to the control variant.
Is endoscopic sinus surgery sufficient to modify the evolution of adult AERD? Aspirin desensitization as a maintenance factor: systematic review
Authors: Conti Diego M. , Correa Eduardo J. , Scadding Glenis K.
Published: September 2023

Introduction

Aspirin desensitization (AD) and aspirin therapy after desensitization (ATAD) are therapeutic interventions for patients with aspirin-exacerbated respiratory disease (AERD). Our aim is to investigate whether its addition to endoscopic sinus surgery (ESS) improves the overall prognosis of the disease.

Methods

A systematic review of the current literature including adult patients with a positive diagnosis of AERD undergoing endoscopic sinus surgery (ESS) in the context or in absence of upper airway comorbidity, prior to AD + ATAD.

Conclusion

This review concludes that the surgical approach is beneficial in AERD, but its effects are short—lived. Surgery should be considered initially with subsequent AD + ATAD in AERD patients, due to the sustained improvement achieved compared to those receiving ESS alone.
Human engineered cardiac tissue model of hypertrophic cardiomyopathy recapitulates key hallmarks of the disease and the effect of chronic mavacamten treatment
Authors: Wang Kai , Schriver Brian J. , Aschar-Sobbi Roozbeh , Yi Alex Y. , Feric Nicole T. , Graziano Michael P.
Published: September 2023

Introduction: The development of patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offers an opportunity to study genotype-phenotype correlation of hypertrophic cardiomyopathy (HCM), one of the most common inherited cardiac diseases. However, immaturity of the iPSC-CMs and the lack of a multicellular composition pose concerns over its faithfulness in disease modeling and its utility in developing mechanism-specific treatment.

Methods: The Biowire platform was used to generate 3D engineered cardiac tissues (ECTs) using HCM patient-derived iPSC-CMs carrying a β-myosin mutation (MYH7-R403Q) and its isogenic control (WT), withal ECTs contained healthy human cardiac fibroblasts. ECTs were subjected to electro-mechanical maturation for 6 weeks before being used in HCM phenotype studies.

Results: Both WT and R403Q ECTs exhibited mature cardiac phenotypes, including a lack of automaticity and a ventricular-like action potential (AP) with a resting membrane potential < −75 mV. Compared to WT, R403Q ECTs demonstrated many HCM-associated pathological changes including increased tissue size and cell volume, shortened sarcomere length and disorganized sarcomere structure. In functional assays, R403Q ECTs showed increased twitch amplitude, slower contractile kinetics, a less pronounced force-frequency relationship, a smaller post-rest potentiation, prolonged AP durations, and slower Ca2+ transient decay time. Finally, we observed downregulation of calcium handling genes and upregulation of NPPB in R403Q vs. WT ECTs. In an HCM phenotype prevention experiment, ECTs were treated for 5-weeks with 250 nM mavacamten or a vehicle control. We found that chronic mavacamten treatment of R403Q ECTs: (i) shortened relaxation time, (ii) reduced APD90 prolongation, (iii) upregulated ADRB2, ATP2A2, RYR2, and CACNA1C, (iv) decreased B-type natriuretic peptide (BNP) mRNA and protein expression levels, and (v) increased sarcomere length and reduced sarcomere disarray.

Discussion: Taken together, we demonstrated R403Q ECTs generated in the Biowire platform recapitulated many cardiac hypertrophy phenotypes and that chronic mavacamten treatment prevented much of the pathology. This demonstrates that the Biowire ECTs are well-suited to phenotypic-based drug discovery in a human-relevant disease model.
Chlorpromazine affects autophagy in association with altered Rag GTPase–mTORC1–TFEB signaling
Authors: Li Ningning , Rao Lingling , Zhao Xueqing , Shen Junwen , Su Dan , Ma Guoqiang , Sun Shan , Ma Qilian , Zhang Li , Dong Chunsheng , Tam Kin Yip , Prehn Jochen H. M. , Wang Hongfeng , Ying Zheng
Published: September 2023

Autophagy is a critical protein and organelle quality control system, which regulates cellular homeostasis and survival. Growing pieces of evidence suggest that autophagic dysfunction is strongly associated with many human diseases, including neurological diseases and cancer. Among various autophagic regulators, microphthalmia (MiT)/TFE transcription factors, including transcription factor EB (TFEB), have been shown to act as the master regulators of autophagosome and lysosome biogenesis in both physiological and pathological conditions. According to the previous studies, chlorpromazine (CPZ), an FDA-approved antipsychotic drug, affects autophagy in diverse cell lines, but the underlying mechanism remains elusive. In our present study, we find that CPZ treatment induces TFEB nuclear translocation through Rag GTPases, the upstream regulators of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Meanwhile, CPZ treatment also blocks autophagosome–lysosome fusion. Notably, we find a significant accumulation of immature autophagosome vesicles in CPZ-treated cells, which may impede cellular homeostasis due to the dysfunction of the autophagy–lysosome pathway. Interestingly and importantly, our data suggest that the expression of the active form of Rag GTPase heterodimers helps in reducing the accumulation of autophagosomes in CPZ-treated cells, further suggesting a major contribution of the Rag GTPase–mTORC1–TFEB signaling axis in CPZ-induced autophagic impairment.
Longitudinal anti-SARS-CoV-2 antibody immune response in acute and convalescent patients
Authors: Pérez-Juárez Horacio , Serrano-Vázquez Angélica , Godínez-Alvarez Héctor , González Enrique , Rojas-Velázquez Liliana , Moran Patricia , Portillo-Bobadilla Tobías , Ramiro Manuel , Hernández Eric , Lau Clara , Martínez Marcela , Padilla Ma. de los Ángeles , Zaragoza Martha E. , Taboada Blanca , Palomares Laura A. , López Susana , Alagón Alejandro , Arias Carlos F. , Ximénez Cecilia
Published: September 2023

Despite global efforts to assess the early response and persistence of SARS-CoV-2 antibodies in patients infected with or recovered from COVID-19, our understanding of the factors affecting its dynamics remains limited. This work aimed to evaluate the early and convalescent immunity of outpatients infected with SARS-CoV-2 and to determine the factors that affect the dynamics and persistence of the IgM and IgG antibody response. Seropositivity of volunteers from Mexico City and the State of Mexico, Mexico, was evaluated by ELISA using the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein for 90 days, at different time points (1, 15, 45, 60, and 90 days) after molecular diagnosis (RT-qPCR). Gender, age range, body mass index (BMI), comorbidities, and clinical spectrum of disease were analyzed to determine associations with the dynamics of anti-SARS-CoV-2 antibodies. On 90 days post-infection, individuals with moderate and asymptomatic disease presented the lowest levels of IgM, while for IgG, at the same time, the highest levels occurred with mild and moderate disease. The IgM and IgG levels were related to the clinical spectrum of disease, BMI, and the presence/absence of comorbidities through regression trees. The results suggest that the dynamics of anti-SARS-CoV-2 IgM and IgG antibodies in outpatients could be influenced by the clinical spectrum of the disease. In addition, the persistence of antibodies against SARS-CoV-2 could be related to the clinical spectrum of the disease, BMI, and the presence/absence of comorbidities.
Comprehensive evaluation of time-varied outcomes for invasive and conservative strategies in patients with NSTE-ACS: a meta-analysis of randomized controlled trials
Authors: Zhao Yi-Jing , Sun Yangyang , Wang Fan , Cai Yuan-Yuan , Alolga Raphael N. , Qi Lian-Wen , Xiao Pingxi
Published: September 2023

Background

Results from randomized controlled trials (RCTs) and meta-analyses comparing invasive and conservative strategies in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are highly debatable. We systematically evaluate the efficacy of invasive and conservative strategies in NSTE-ACS based on time-varied outcomes.

Methods

The RCTs for the invasive versus conservative strategies were identified by searching PubMed, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov. Trial data for studies with a minimum follow-up time of 30 days were included. We categorized the follow-up time into six varied periods, namely, ≤6 months, 1 year, 2 years, 3 years, 5 years, and ≥10 years. The time-varied outcomes were major adverse cardiovascular event (MACE), death, myocardial infarction (MI), rehospitalization, cardiovascular death, bleeding, in-hospital death, and in-hospital bleeding. Risk ratios (RRs) and 95% confidence intervals (Cis) were calculated. The random effects model was used.

Results

This meta-analysis included 30 articles of 17 RCTs involving 12,331 participants. We found that the invasive strategy did not provide appreciable benefits for NSTE-ACS in terms of MACE, death, and cardiovascular death at all time points compared with the conservative strategy. Although the risk of MI was reduced within 6 months (RR 0.80, 95% CI 0.68–0.94) for the invasive strategy, no significant differences were observed in other periods. The invasive strategy reduced the rehospitalization rate within 6 months (RR 0.69, 95% CI 0.52–0.90), 1 year (RR 0.73, 95% CI 0.63–0.86), and 2 years (RR 0.77, 95% CI 0.60–1.00). Of note, an increased risk of bleeding (RR 1.80, 95% CI 1.28–2.54) and in-hospital bleeding (RR 2.17, 95% CI 1.52–3.10) was observed for the invasive strategy within 6 months. In subgroups stratified by high-risk features, the invasive strategy decreased MACE for patients aged ≥65 years within 6 months (RR 0.68, 95% CI 0.58–0.78) and 1 year (RR 0.75, 95% CI 0.62–0.91) and showed benefits for men within 6 months (RR 0.71, 95% CI 0.55–0.92). In other subgroups stratified according to diabetes, ST-segment deviation, and troponin levels, no significant differences were observed between the two strategies.

Conclusions

An invasive strategy is superior to a conservative strategy in reducing early events for MI and rehospitalizations, but the invasive strategy did not improve the prognosis in long-term outcomes for patients with NSTE-ACS.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289579, identifier PROSPERO 2021 CRD42021289579.
Effect of dual antiplatelet therapy prolongation in acute coronary syndrome patients with both high ischemic and bleeding risk: insight from the OPT-CAD study
Authors: Na Kun , Qiu Miaohan , Wei Ningxin , Li Jiayin , Yan Chenghui , Li Jing , Li Yi , Han Yaling
Published: September 2023

Background

In current clinical practice, controversy remains regarding the clinical benefits of prolonged dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients facing high risks of both ischemia and bleeding (“bi-risk”) following percutaneous coronary intervention (PCI). This study aimed to investigate the feasibility of identifying a group of bi-risk ACS patients after PCI using the OPT-BIRISK criteria, emphasizing extended DAPT treatment safety and efficacy beyond 12 months in these bi-risk ACS after PCI in real-world conditions.

Methods

This analysis compared extended DAPT and single antiplatelet therapy (SAPT) at 12–24 months in ACS patients undergoing PCI complicated with both ischemic and bleeding risk as defined by OPT-BIRISK criteria without premature DAPT discontinuation before 9 months or major clinical adverse events within 12 months. This was a post hoc analysis of the Optimal antiPlatelet Antiplatelet Therapy for Chinese Patients with Coronary Artery Disease (OPT–CAD) study. The main research outcome was the incidence of ischemic events within 12–24 months, which was determined as a composite of stroke, myocardial infarction, and cardiac death events. Through propensity score matching (PSM), groups were balanced. For the external validation of the OPT-BIRISK criteria to identify a bi-risk ACS patient, ischemic events, BARC 2, 3, 5 bleeding events, and BARC 3, 5 bleeding events at 5 years were analyzed.

Results

The total number of ACS patients analyzed in this analysis was 7,049, of whom 4,146 (58.8%) were bi-risk patients and 2,903 (41.2%) were not. The frequency of ischemic events was significantly different between the two groups at 5 years (11.70% vs. 5.55%, P < 0.001), and the incidence of BARC 2,3,5 bleeding was significantly higher in the bi-risk group (6.90% vs. 4.03%, P < 0.001) than in the non-bi-risk group. Among the bi-risk patients without any clinical adverse events within 12 months that underwent extended DAPT treatment (n = 2,374, 75.7%) exhibited a lower risk of stroke at 12–24 months (1.10% vs. 2.10%, P = 0.036) relative to those that underwent SAPT (n = 763, 24.3%), while bleeding risk did not differ significantly between these groups. PSM cohort analysis results were consistent with those of overall group analyses.

Conclusion

In conclusion, the findings showed that using the OPT-BIRISK criteria could help physicians identify ACS patients at a high risk of developing recurrent ischemia and bleeding episodes after PCI. Compared to antiplatelet monotherapy, a strategy of extended DAPT may offer potential benefits in lowering the risk of stroke without carrying a disproportionately high risk of serious bleeding problems among these patients who were event-free after a year of DAPT.
Conducting a child injury prevention RCT in the wake of COVID-19: lessons learned for virtual human subjects research
Authors: Prokos Sophia , Damashek Amy , Morrongiello Barbara , Arbour Emilie , Belachew Bethelhem , Zafreen Farzana
Published: September 2023

Unintentional injury is the leading cause of death among children in the United States, and children living in low-income households are particularly at risk for sustaining unintentional injuries. Close parental supervision has been found to reduce young children's risk for injury; however, few studies have examined interventions to increase parental supervision. This paper discusses COVID-19 related modifications that were made to a federally funded randomized controlled trial to reduce low-income children's risk for unintentional injury. The study's procedures (data collection and intervention delivery) had to be transitioned from in-person to a fully virtual format. Modifications that were made to the study included use of: participant cell phones to conduct data collection and intervention sessions; virtual meeting software to conduct sessions with participants and; an online platform to collect questionnaire data. In addition, many modifications were required to complete the in-home observation virtually. In terms of feasibility, the investigators were able to collect all of the data that was originally proposed; however, recruitment and retention was more challenging than anticipated. Lessons learned during the modification process are included to provide guidance to researchers seeking to conduct virtual human subjects research in the future.
COVID-19-related school closures and mathematical performance—findings from a study with grade 3 students in Germany
Authors: Gasteiger Hedwig , Sachse Karoline A. , Schumann Kristoph , Gerve Mona , Schulz Axel , Engelbert-Kocher Maria
Published: September 2023

Introduction

Due to the COVID-19 pandemic, measures were taken that had a considerable impact on the situation in schools. In Germany, these measures lasted more than a year and ranged from school closures and distance learning to alternating teaching phases with small groups. In the present study, we examined whether third-grade students’ mathematics performance changed in different content domains before and after the COVID-19-related changes in school.

Methods

In a repeated cross-sectional design, we compared two cohorts of third graders (2019: N = 1,905; 2021: N = 3,203) based on standardized mathematics tests, constructed according to the German National Educational Standards, which allowed for a differential competence diagnostic for five content domains. Generalized linear mixed models were used to model item and person properties and assess their effects on performance.

Results

There was a significant drop in performance overall. While the drop in the content domain Numbers & Operations was smaller than the overall drop in performance, the content domains Space & Shape and Data, Frequency, Probability were more affected.

Discussion

The findings of this study may be explained by the results of numerous surveys of students, teachers, and parents, which indicated that a lot of time was spent on exercises and reproduction tasks during distance learning.
Perspectives of children and young people with a sensory loss: opportunities and experiences of engagement in leisure activities
Authors: Hannah Elizabeth Fraser Selkirk
Published: September 2023

Research indicates that engaging in leisure activities has a positive effect on the wellbeing, development, and quality of life of children and young people with disabilities. However, there appears to be limited literature focusing on the participation of children and young people with a sensory loss in leisure activities and few studies which have gathered data from children and young people. To address this gap, this study explores the perspectives of children and young people with a sensory loss (visual impairment and/or deaf) about opportunities to participate in leisure activities with other children/young people and their experiences. The research was conducted in one locality in Scotland. Sixteen children and young people with a sensory loss from primary and secondary schools participated in four virtual focus groups. Findings revealed that the participants enjoyed having opportunities to be with other children outwith the school context. Psychosocial benefits from participation in leisure activities with other children with a sensory loss included feelings of not being alone and of being understood. Findings emphasised the lack of opportunities for children and young people with a sensory loss to engage in leisure activities in the community as well as barriers and facilitators to participation, such as communication. The study highlights the importance of increasing societal awareness of the needs of individuals with sensory loss and providing opportunities to engage in leisure activities in accessible environments.