bluuebunny/crossref_metadata_2025 huggingface dataset:
Production studies of the disinfectant “Enzidez”
Authors: Kozhyn V. , Salata V. , Kukhtyn M. , Horiuk Y. , Matviishyn T. S.
Published: October 2023

The main task of carrying out disinfection measures in veterinary medicine is to break the mechanisms of pathogen transmission through objects and objects of the environment from one animal to another. Therefore, disinfection measures are the basis of safe keeping of animals, carrying out treatment and preventive measures in clinics of veterinary medicine. The purpose of this study was to determine the effectiveness of the created disinfectant “Enzidez” in the production conditions of veterinary medicine clinics. The surfaces of walls, floors and tables were disinfected by wiping. Surgical, dental instruments and veterinary products by immersion in a solution or wiping. Before and after treatment, washings were taken for microbiological examination by generally accepted methods. It was established that the effectiveness of disinfection with “Enzidez” in a concentration of 0.25–1.00 % of walls, floors, tables in veterinary clinics, for their various microbial and organic contamination, was 100 %. Only in one case, after disinfection with a 0.25 % solution, microorganisms were released from the floor surfaces, amounting to 3.8 ± 0.1×101 CFU/cm3 of wash. However, even under this regime, the disinfection efficiency was 99.99 %. The effectiveness of disinfection with “Enzidez” during the presterilization cleaning of surgical instruments and veterinary products revealed that the main microflora before treatment was represented by staphylococci, micrococci, corynebacteria, streptococci, yeast, coliform bacteria in the amount of 103 to 105 CFU/cm3 of washing. After treatment with a concentration of 0.25 to 1.00 %, the disinfectant provided a bactericidal effect, as a result of which microorganisms were not isolated from the surfaces in any case. Therefore, we believe that the developed means for disinfection, pre-sterilization cleaning and sterilization in veterinary medicine clinics “Enzidez” is a highly effective disinfectant for use in a concentration of 0.25–1.0 % and exposure of solutions for 15–30 minutes.
Sultan Mehmed’in Eflâk Prensi III. Vlad Drakula (Kazıklı Voyvoda) İle Olan Mücadelesi
Authors: HEPER Yusuf
Published: October 2023

Eflâk Prensi Vlad Țepeş, Sigishoara kentinde 1431 yılında dünyaya geldi. Çocukluk yılları Transilvanya’da geçti. Daha sonra babasının Edirne’ye gelerek iki oğlunu rehin bırakmasıyla birlikte onun Anadolu topraklarında 6 yıl süren esaret hayatı başladı. 1448 yılında yakaladığı ilk fırsatta Osmanlı desteğiyle Eflâk voyvodası oldu. Ne var ki kuzeni II. Vladislav’ın Eflâk’a gelişiyle Boğdan’a geçti. Bir süre sonra Macar desteğiyle ikinci kez Eflâk voyvodalığına geçerek bu sefer silahlarını Osmanlı’ya karşı doğrulttu. Vlad Țepeş, Osmanlı’ya ödemesi gereken yıllık haracı göndermediği gibi Tuna Yalılarında bulunan Türk köy ve kasabalarını ateşe verdi. Bunun üzerine sultan Mehmed büyük bir orduyla Eflâk seferine çıktı. O, güçlü olan rakibinin karşısına çıkmaktansa stratejik geri çekilme yöntemiyle Fatih’i durdurmayı denedi. Hatta sultan Târgovişte’ye gelmezden evvel bir gece baskınıyla onu öldürmeyi dahi planladı. Ancak Fatih, Eflâk ordusuyla karşılaşmayınca onun yerine voyvodalığı kardeşi Radu’ya verdi
Rumeli’de Kurulan İlk Osmanlı Şehri: Ergene (Kuruluşundan XVI. Yüzyıl Sonlarına Kadar)
Authors: ATEŞ Hacer
Published: October 2023

Osmanlılar Rumeli’ye geçtikten sonra iskân faaliyetleri neticesinde mevcut Bizans şehirlerini geliştirmişlerdir. İlerleyen zaman içinde Rumeli coğrafyasında yeni şehirler de kurulmuştur. Rumeli’de Osmanlılar tarafından kurulan ilk şehir olma özelliğini taşıyan Ergene şehri Sultan II. Murad’ın Ergene Nehri üzerinde yaptırdığı taş köprü etrafında kurulmuş bir yerleşim ünitesidir. XV. yüzyılda Ergene olan ismi buradaki XVI. yüzyılda köprüye istinaden Cisr-i Ergene da anılmaya başlanmış, XIX. yüzyılda ise Uzunköprü ismini almıştır. Ergene şehri taş köprü civarında yine Sultan II. Murad’ın yaptırdığı imaret ve diğer vakıf yapıları etrafında gelişme göstermiştir. Vakıf yapıları bu Bu çalışmada öncelikli olarak tahrir defterleri ve muhtelif arşiv vesikaları incelenerek Osmanlı döneminde Rumeli’de bir şehrin oluşum ve şehirleşmenin hangi unsurlar çerçevesinde geliştiği Ergene şehri özelinde ele alınacaktır.
Directional Antenna for High Density Access Point Stadion Coverage
Authors: Radiles Hasdi , Sutoyo Sutoyo , Pratama Dio Alam , Faizal Ahmad
Published: October 2023

The existence of a Wi-Fi network in the stadium is an important issue because of the many requests for communication access from spectators. Implementation of HD-AP Wi-Fi using directional antennas is one solution to avoid severe interference. This study simulates the coverage of the AP installed on the roof of the tribune station. The simulator is designed using HPBW Elevations 200, 400 and 600. Testing also considers the use of the appropriate transmit power, to obtain the appropriate HPBW combination to avoid interference. The analysis is carried out by comparing the reception of the strongest signal with reception at the sector border. The results of the study show that Antenna directional with HPBW Elevation 400 is more effective in serving users in three service sectors.
Emergency Tower System For An Accident
Authors: Nurrizka Muhammad Raihan , Loniza Erika , Mukti Taqwa Anggara , Priyanto Oki
Published: October 2023

An emergency is an accident that cannot be predicted when it will happen. Emergency situation is a patient's clinical condition that need immediate medical action, to save lives and prevent further disability. campus is a place with high mobility of the academic community, so the potential for an emergency to occur in the campus area is quite large Apart from accidents, emergency cases that require prompt and appropriate treatment are sudden cardiac arrest. The life expectancy of cardiac arrest sufferers is very dependence on the competence of helpers to provide. Therefore, the process of handling emergency cases in the campus area can be carried out by developing a risk management ecosystem through an emergency tower that is integrated in the Detector Tower wirelessly. Emergency tower is a tower to provide information related to an emergency situation. This tower use an esp8266 as microcontroller to send information, sirins for an indicator to make an announcement there is an accident. Door lock to lock first aid box that only opens when push button got pressed. The result of emergency tower are can send alert information and do two-way communication with the Detector Tower, which can provide emergency handling through the Detector Tower installed at the location of the officer in charge. While waiting the Emergency tower is equipped with a first aid kit box that can be used as well as CCTV that will monitor events in the area. The emergency tower system has 100% that can help to handle emergency situation.
Estrategias para la prevención de conflictos entre alumnos en el aula
Authors: Velastegui Hernández Rommel Santiago , Arroba López Gissela Alexandra , Melo Fiallos Diego Fernando , Mayorga Ases María José
Published: October 2023

Introducción.  Los conflictos entre alumnos en el aula pueden definirse como desacuerdos, discusiones o disputas entre alumnos que perturban el ambiente de aprendizaje. Mediante la aplicación de estrategias para la prevención de conflictos entre alumnos, los profesores pueden crear un entorno de aprendizaje más positivo y productivo para todos los estudiantes. Existen varias estrategias que los profesores pueden utilizar para prevenir los conflictos entre alumnos en el aula. Implica la creación de una cultura de aula que valore el respeto, la empatía y la comunicación abierta, así como el establecimiento de unas expectativas claras de comportamiento y de las consecuencias de su incumplimiento. Cuando surgen conflictos, es esencial abordarlos con prontitud y eficacia. Los profesores pueden ayudarles a desarrollar las habilidades y actitudes necesarias para resolver conflictos de forma eficaz y respetuosa. Objetivo. Conceptualizar estrategias para la prevención de conflictos entre alumnos en el aula. Metodología.  Para la metodología propuesta contiene diez pasos: 1. Diseño de la investigación. 2. Tipo de investigación. 3. Nivel de investigación. 4. Modalidad de investigación. 5. Métodos, procedimientos y técnicas de investigación, contemplando. 6. Población o grupo de estudio. 7. Criterios de inclusión. 8. Criterios de exclusión. 9. Criterios de eliminación. 10. Aspectos. Resultados. Los resultados obtenidos se detallan a continuación: Establecer expectativas y normas claras. Fomentar relaciones positivas. Utilizar técnicas eficaces de gestión del aula. Fomentar la comunicación abierta. Enseñar técnicas de resolución de conflictos. Abordar la intimidación y el acoso. Ofrecer oportunidades de colaboración. Tener en cuenta las necesidades individuales de cada alumno. Evaluar y ajustar las estrategias. Conclusión.  Los conflictos entre alumnos en el aula pueden prevenirse mediante diversas estrategias. Estas estrategias incluyen el establecimiento de expectativas y normas claras, la promoción de relaciones positivas, y otras considerando la promoción de oportunidades para la colaboración y la consideración de las necesidades individuales de los estudiantes. La mejora continua de las estrategias de prevención de conflictos es la última estrategia clave para prevenir los conflictos de los alumnos en el aula. Esto implica un compromiso con el desarrollo profesional continuo, la búsqueda de nuevos recursos e información, y mantenerse al día con las últimas investigaciones y las mejores prácticas en este campo. Área de estudio general: Educación. Área de estudio específica: Prevención de conflictos en el aula.
«New economic reality» as an intermediate phase of development between capitalist and associated modes of production
Authors: Chikanova Elena S. , Brizhak Olga V.
Published: October 2023

The emergence of qualitatively new phenomena of social and economic life, economic theory receives impulses of its renewal and is being modernized. Among such phenomena are the new economic reality, its scale, complexity, as well as the saturation of acute contradictions predetermine the difficulties of its theoretical interpretation and significant differences in the interpretations of its content. At the same time, these peculiarities of the new economic reality make necessary to attract to its theoretical study the cognitive possibilities of the theory of modes of production. Drawing on such opportunities, the authors come to the conclusion that the new economic reality represents a special phase in the progressive movement of the capitalist mode of production. The boundary of such a phase is set by the transition of the threshold of measures in the accumulation of problems that are not provided with adequate solutions, generated by long and deep technological shifts, as well as related socio-economic transformations. A new economic reality arises in the process of transformation of the system of the capitalist mode of production, within which the prerequisites of the associated mode of production are intensively created and accumulated. The formation of a special theory of a new economic reality capable of interpreting a variety of factors characteristic of various aspects of the corresponding phenomenon makes possible to build a holistic picture of a special phase of the development of the capitalist mode of production system, as well as to develop applied tools that are in demand in the process of regulating the most important processes of this phase. The research conducted by the authors is focused on: defining a special subject area of the specified theory in the general space of the evolution of economic theory; developing a method of its research, providing the needs of its formation and development. The article contains practical recommendations for realizing the cognitive potential of the theory of new economic reality. The main results of the theoretical study carried out belong to one of the new directions in the development of economic theory, which predetermines the debatable nature of the conceptual provisions, final conclusions and practical recommendations received by the authors. In the process of research, the possibilities of the dialectical method, modern versions of the systemic and evolutionary approaches, as well as the resources of a number of theories were realized: the mode of production; capital; socio-economic transformations; personification of economic relations; threshold measures in the development of the phenomenon.
Risk-Oriented Model of HR-Management at the Enterprise (Theoretical and Methodological Aspects)
Authors: Stozhko Dmitrii K. , Stozhko Konstantin P.
Published: October 2023

The actuality of developing theoretical and methodological approaches to the formation of a risk-based model of enterprise personnel management is due to the growing macroeconomic instability and turbulence in the current crisis. The reasons for this global economic crisis are the gradual depletion of resources, difficulties in the transition to a new technological structure and compliance with its requirements, unfair competition that has developed over the past decades in the global markets, and growing opposition of the «collective West» to other centers of the world development. The aim of the study is to determine the theoretical and methodological aspects of the formation of a risk-based model of enterprise personnel management in the new reality based on comparative analysis and assessment of existing opportunities for optimizing economic activities, as well as assessing the key factors that determine the quality of modern personnel management. The objectives of the study are: analysis of the morphology of personnel risks and methods for their classification; determination and evaluation of qualitative features of a risk-based model of enterprise personnel management; development of a general algorithm for the formation of this model, taking into account the requirements of the internal and external environment of the enterprise. The study used a dialectical approach, methods of modeling (reconstruction, decomposition) and forecasting (extrapolation), structural-functional and program-targeted analysis. An algorithm for the formation of a risk-based model of enterprise personnel management is proposed, which is presented as a system of variable behavior management of business entities (enterprise personnel) in the context of building their multi-vector development strategy. The morphology of personnel risks is disclosed; the main principles and methods of work with personnel risks at different stages of their genesis are identified and characterized. The most promising organizational and economic tools for practical use of risk-based model of enterprise personnel management are identified. As a dominant condition for functioning of this model, the need to develop broad self-government within the framework of the operational and economic activities of specific divisions of enterprises is argued. The results of the study can be used in the personnel policy of enterprises as part of their operational and strategic reengineering.
Patient Centricity in Skin Treatments: Global Meeting of Experts in Dermatology
Authors: Boreham Helen
Published: October 2023

During this symposium, global experts in dermatology gave a series of lectures focused on skin treatments and their benefits for patients. Giuseppe Micali, University of Catania, Italy, provided a non-invasive skin imaging perspective on the skin journey over time, exploring the changes in the functional integrity of ageing skin, and associated dermatological needs. Positive findings from a clinical study evaluating U-Life™ 10 (Relife Menarini Group, Florence, Italy), a 10% urea cream, in the treatment of senile xerosis were also presented. The second lecture, presented by Giovanni Pellacani, Sapienza University, Rome, Italy, reviewed the pathogenesis of eczema, and the key role of oxidation in skin barrier impairment and inflammation. A recent study evaluating the clinical performance of Relizema™ cream (Menarini Group), a steroid-free medical device, for topical use demonstrated that it effectively reduced the severity of symptoms in adults with atopic and contact dermatitis, and was well-tolerated. The final presentation by Micali focused on salicylic acid-based products containing active ingredients that target multiple pathogenetic factors of acne. Findings from a multicentre, prospective, observational study of this new salicylic acid-based acne daily regimen showed promising improvements in patients with mild acne.
Penanganan Sampah Berbasis Pemberdayaan Masyarakat di Kabupaten Labuhanbatu
Authors: Sitorus Jonni , Lubis Siti Masliyah , Zetri Marlina , Husni Nobrya
Published: October 2023

Penelitian ini bertujuan untuk mendeskripsikan pola penanganan sampah serta upaya PemerintahDaerah Kabupaten Labuhanbatu dalam penanganan sampah. Penelitian ini dianalis secara kualitatifdengan pendekatan deskriptif dan kuantitatif dengan pendekatan statistic sederhana (tanpa ujistatistik). Hasil penelitian menunjukkan bahwa pola penanganan sampah di KabupatenLabuhanbatu adalah pengangkutan sampah dari sumbernya langsung ke Tempat Pemrosesan Akhir(TPA) sehingga TPA kelebihan kapasitas. Pemberdayaan masyarakat dalam penanganan sampahdi Kabupaten Labuhanbatu masih sangat minim, dengan persentase jumlah masyarakat yangpernah mengikuti program dan kegiatan pemberdayaan masyarakat yang dilakukan olehPemerintah Daerah maupun instansi lain per masing-masing indikator penilaian adalah sebagaiberikut: penyuluhan kesehatan lingkungan (10,16%); sosialisasi tentang penanganan sampah dankegiatan sejenisnya (13,115%); keikutsertaan anggota/pengurus organisasi peduli terhadappenanganan sampah (6,885%); pelatihan pengelolaan sampah menjadi bernilai ekonomis(6,885%); mendapat kesempatan bekerja dalam pengelolaan daur ulang sampah (1,311%);mendapat fasilitas pengelolaan sampah (1,311%); mendapat modal usaha pengelolaan sampah(1,311%); mendapat keuntungan secara ekonomi dari pengelolaan sampah (2,295%);menghasilkan beberapa produk dari pengelolaan daur ulang sampah (4,262%); dan upayaperlindungan dari Pemda saat terjadi konflik penanganan sampah (3,607%). PemerintahKabupaten Labuhanbatu telah memiliki 2 peraturan dan perundang-undangan terkait penanganandan pengelolaan sampah, yaitu Peraturan Daerah Kabupaten Labuhanbatu Nomor 8 Tahun 2017tentang Pengelolaan Sampah, dan Peraturan Bupati Labuhanbatu Nomor 48 Tahun 2021 tentangPelimpahan Sebagian Kewenangan Pengelolaan Persampahan kepada Camat di LingkunganPemerintah Kabupaten Labuhanbatu.Kata kunci: penanganan sampah, pemberdayaan masyarakat, kebijakan pemerintah
Biomechanical evaluation of novel intra- and extramedullary assembly fixation for proximal humerus fractures in the elderly
Authors: Zhu Zhengguo , Chang Zuhao , Zhang Wei , Qi Hongzhe , Guo Hao , Li JiaQi , Qi Lin , Nie Shaobo , Tang Peifu , Liang Yonghui , Wei Xing , Chen Hua
Published: October 2023

Purpose: A novel intra- and extramedullary assembly fixation method was introduced, which achieved good clinical results in complex proximal humeral fractures; however, evidence of its comparability with traditional fixation is lacking. This biomechanical study aimed to compare it with traditional fixation devices in osteoporotic proximal humeral fractures.

Methods: Three-part proximal humeral fractures with osteopenia were created on 12 pairs of fresh frozen humerus specimens and allocated to three groups: 1) lateral locking plate, 2) intramedullary nail, and 3) intra- and extramedullary assembly fixation. The specimens were loaded to simulate the force at 25° abduction. Thereafter, an axial stiffness test and a compound cyclic load to failure test were applied. Structural stiffness, number of cycles loaded to failure, and relative displacement values at predetermined measurement points were recorded using a testing machine and a synchronized 3D video tracking system.

Results: In terms of initial stiffness and the number of cycles loaded to failure, the intra- and extramedullary assembly fixation group showed notable improvements compared to the other groups (p <0.017). The mean relative displacement value of measurement points in the intra- and extramedullary assembly fixation group was smaller than that in the other two groups. However, there was no significant difference until 10,000 cycles. The mean relative displacement of the intramedullary nail group (3.136 mm) exceeded 3 mm at 7,500 cycles of loading.

Conclusion: In this test model, axial fixation can provide better mechanical stability than non-axial fixation. The intra- and extramedullary assembly fixation is better able to prevent the varus collapse for elderly proximal humeral fractures with posteromedial comminution.
Divergent features of ERβ isoforms in triple negative breast cancer: progress and implications for further research
Authors: Yan Shunchao , Wang Jinpeng , Chen Hong , Zhang Duo , Imam Murshid
Published: October 2023

Estrogen receptor β (ERβ) was discovered more than 20 years ago. However, the extent and role of ERβ expression in breast cancer remain controversial, especially in the context of triple-negative breast cancer (TNBC). ERβ exists as multiple isoforms, and a series of studies has revealed an inconsistent role of ERβ isoforms in TNBC. Our recent results demonstrated contrasting functions of ERβ1 and ERβ2/β5 in TNBC. Additional research should be conducted to explore the functions of individual ERβ isoforms and develop targeted drugs according to the relevant mechanisms. Consequently, a systematic review of ERβ isoforms is necessary. In this review, we overview the structure of ERβ isoforms and detail what is known about the function of ERβ isoforms in normal mammary tissue and breast cancer. Moreover, this review highlights the divergent features of ERβ isoforms in TNBC. This review also provides insights into the implications of targeting ERβ isoforms for clinical treatment. In conclusion, this review provides a framework delineating the roles and mechanisms of different ERβ isoforms in TNBC and sheds light on future directions for basic and clinical research.
Pharmacokinetic and pharmacodynamic studies of nicotine in rat brain: a simultaneous investigation of nicotine metabolites and the release of neurotransmitters in vivo
Authors: Guo Lulu , Mao Jian , Zhang Qidong , Fan Wu , Wang Dingzhong , Li Zhonghao , Huang Jiaqiang , Xie Jianping
Published: October 2023

Introduction: The body’s ability to metabolize nicotine and the disposition of nicotine in the brain are important determinants of its exposure. Limited knowledge about the near real-time changes of neurochemicals during the brain nicotine metabolic process hinders the recognition of its multiple neuropharmacological effects.

Methods: An online microdialysis coupled with UHPLC-HRMS/MS method for the in vivo multi-analysis of nicotine metabolites and several neurotransmitters in rat brain was developed. Whether the systemic modulation of metabolic enzyme CYP2B would modulate nicotine pharmacokinetics and local neurochemical effects was further investigated.

Results: The dynamic profiles of over 10 nicotine metabolites and neurotransmitters were simultaneously obtained after a single injection of nicotine (2 mg·kg−1, i.p.) using the new method. Proadifen pretreatment (50 mg·kg−1·d−1, i.p., 4 days) caused significant inhibition of brain CYP2B1 activity. When exposed to nicotine, the brain Cmax of nicotine was 1.26 times higher and the levels of nicotine metabolites, nornicotine, and nicotine-N-oxide, were decreased by 85.3% and 34.4% in proadifen-pretreated rats. The higher level of brain nicotine induced a greater release of dopamine, serotonin, glutamate, and γ-amino-butyric acid in the nucleus accumbens. The concentrations of nicotine and dopamine were positively correlated, and the average levels of γ-amino-butyric acid and serotonin were 2.7 and 1.2 times higher, respectively, under the inhibition of nicotine metabolism.

Discussion: These results demonstrated that inhibiting nicotine metabolism in rats can enhance the residence of brain nicotine and its local neurotransmitter effects. The metabolic activity of nicotine under different physiological conditions could regulate nicotine’s bioavailability and its resulting pharmacology.
A co-produced national climate change risk and vulnerability assessment framework for South Africa
Authors: Ziervogel Gina , Taylor Anna
Published: October 2023

Introduction

There are mounting demands to undertake climate risk and vulnerability (CRV) assessments for policy, planning, funding, insurance, and compliance reasons. In Africa, given the adaptation imperative, this is particularly important. Increasingly, it has become clear that sub-national assessments are needed to inform adaptation practice. However, there has been relatively little guidance on how to undertake these more local assessments and aggregate them making it difficult for national governments to know the extent and variability of climate vulnerability and risk across the country.

Methods

In South Africa, the national government, led by the Department of Forestry, Fisheries and the Environment (DFFE), undertook to establish a common framework to guide the development and review of CRV assessments. This paper presents the framework that was co-developed through a series of engagements with stakeholders active in implementing and supporting CRV assessments.

Results

The framework is intended to provide guidance on what to consider when undertaking CRV assessments within diverse South African contexts in order to enable alignment, comparison, and aggregation between them and work towards an effective climate adaptation response across scales. Rather than standardizing a methodology, the framework promotes the use of a standard set of concepts as the basis for each assessment and profiles a diversity of methods, tools and data sources for applying the concepts in a contextually sensitive way. This provides a flexible yet structured sequence of three interlinked steps in a risk and vulnerability assessment process, namely: (1) Planning, (2) Scoping and (3) Assessing. The framework guides users through the choice and application of three assessment depths, depending on decision-context, resourcing and extent of pre-existing data and information. It encourages the integration of participatory and indicator-based methods through an impact chain approach, profiling more than 30 freely available tools and resources. This process builds a strong evidence base and a deepening set of engagements and shared understanding between relevant stakeholders, upon which to act.

Discussion

This South African process can provide insight and support for actors driving the climate agenda in other countries looking to develop comparable assessments as the basis to drive equitable and transformative climate action and learning.
Direct wire pacing during measurement of fractional flow reserve: A randomized proof-of-concept noninferiority crossover trial
Authors: Faurie Benjamin , Acheampong Angela , Abdellaoui Mohamed , Dessus Ilona , Monsegu Jacques , Wintzer-Wehekind Jérôme
Published: October 2023

Background

Adenosine administration for fractional flow reserve (FFR) measurement may induce heart pauses.

Aims

To assess the accuracy and tolerability of direct wire pacing (DWP) during measurement of FFR.

Methods

Adults with at least one intermediate coronary artery stenosis (40%–80%) were consecutively enrolled between June 2021 and February 2022 in this randomized, noninferiority, crossover trial (NCT04970082) carried out in France. DWP was applied (DWP) or not (standard method) through the pressure guidewire used for FFR measurement during adenosine-induced maximal hyperaemia. Subjects were randomly assigned to the allocation sequence (DWP first or standard first). A 2-minute washout period was observed between the two FFR measurements performed for each stenosis. The primary endpoint was the reproducibility of FFR measurements between methods.

Results

A total of 150 focal lesions, presented by 94 subjects, were randomized (ratio: 1:1). The FFR values obtained with each method were nearly identical (R = 0.98, p = 0.005). The mean FFR difference of 0.00054 (95% confidence interval: 0.004 to 0.003) showed the noninferiority of FFR measurement with DWP vs. that with the standard method. Higher levels of chest discomfort were reported with DWP than with the standard method (0.61 ± 0.84 vs. 1.05 ± 0.89, p < 0.001), and a correlation was observed between the electrical sensations reported with DWP and chest discomfort (p < 0.001). Pauses (n = 20/148 lesions) were observed with the standard method, but did not correlate with chest discomfort (p = 0.21). No pauses were observed with DWP.

Conclusions

DWP during FFR measurement resulted in accurate and reproducible FFR values, and eliminated the pauses induced by adenosine.
Impact of daily artificial gravity on autonomic cardiovascular control following 60-day head-down tilt bed rest
Authors: Hoenemann J.-N. , Moestl S. , Diedrich A. , Mulder E. , Frett T. , Petrat G. , Pustowalow W. , Arz M. , Schmitz M.-T. , Heusser K. , Lee S. M. C. , Jordan J. , Tank J. , Hoffmann F.
Published: October 2023

Impaired cardiovascular autonomic control following space flight or immobilization may limit the ability to cope with additional hemodynamic stimuli. Head-down tilt bedrest is an established terrestrial analog for space flight and offers the opportunity to test potential countermeasures for autonomic cardiovascular deconditioning. Previous studies revealed a possible benefit of daily artificial gravity on cardiovascular autonomic control following head-down tilt bedrest, but there is a need for efficiency in a long-term study before an artificial gravity facility would be brought to space. We hypothesized that artificial gravity through short-arm centrifugation attenuates functional adaptions of autonomic function during head-down tilt bed rest. 24 healthy persons (8 women, 33.4 ± 9.3 years, 24.3 ± 2.1 kg/m2) participated in the 60-day head-down tilt bed rest (AGBRESA) study. They were assigned to three groups, 30 min/day continuous, or 6(5 min intermittent short-arm centrifugation, or a control group. We assessed autonomic cardiovascular control in the supine position and in 5 minutes 80° head-up tilt position before and immediately after bed rest. We computed heart rate variability (HRV) in the time (rmssd) and frequency domain, blood pressure variability, and baroreflex sensitivity (BRS). RR interval corrected rmssd was reduced supine (p = 0.0358) and during HUT (p = 0.0161). Heart rate variability in the high-frequency band (hf-RRI; p = 0.0004) and BRS (p < 0.0001) decreased, whereas blood pressure variability in the low-frequency band (lf-SBP, p = 0.0008) increased following bedrest in all groups. We did not detect significant interactions between bedrest and interventions. We conclude that up to daily 30 min of artificial gravity on a short-arm centrifuge with 1Gz at the center of mass do not suffice to prevent changes in autonomic cardiovascular control following 60-day of 6° head-down tilt bed rest.

Clinical Trial Registration: https://drks.de/search/en/trial/DRKS00015677, identifier, DRKS00015677
Case Report: Correlation between pulmonary capillary wedge pressure and left-ventricular diastolic pressure during treatment with veno-arterial extracorporeal membrane oxygenation
Authors: Kalra Rajat , Gaisendrees Christopher , Alexy Tamas , Kosmopoulos Marinos , Jaeger Deborah , Schlachtenberger Georg , Raveendran Ganesh , Bartos Jason A. , Gutierrez Bernal Alejandra , John Ranjit , Wahlers Thorsten , Yannopoulos Demetris
Published: October 2023

Background

Pulmonary capillary wedge pressure (PCWP) is often used as a surrogate for left-ventricular end-diastolic pressure in patients (LVEDP) who are on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support for cardiogenic shock and cardiac arrest. However, the correlation between PCWP and LVEDP is not clear in the setting of V-A ECMO usage. We sought to evaluate this correlation in this case series.

Methods

Patients were referred to our cardiac catheterization laboratory for invasive hemodynamic studies to assess their readiness for VA-ECMO decannulation. All patients underwent simultaneous left and right heart catheterization. Using standard techniques, we measured PCWP and LVEDP simultaneously. Continuous variables were reported as medians with interquartile ranges. The correlation between PCWP and LVEDP was evaluated using simple linear regression and reported as R2.

Results

Four patients underwent invasive hemodynamic studies 4 (2.5, 7) days after VA-ECMO cannulation. All four patients had suffered in-hospital cardiac arrest and had been put on VA-ECMO. At the baseline level of VA-ECMO flow of 4.1 (3.8, 4.4) L/min, the median LVEDP and PCWP were 6 (4, 7.5) mmHg and 12 (6.5, 16) mmHg, respectively. At the lowest level of VA-ECMO flow of 1.9 (1.6, 2.0) L/min, the median LVEDP and PCWP was 13.5 (8.5, 16) mmHg and 15 (13, 18) mmHg, respectively. There was a poor correlation between the simultaneously measured PCWP and LVEDP (R2 = 0.03, p = 0.66).

Conclusions

The PCWP may not correlate well with LVEDP in patients treated with VA-ECMO, particularly at high levels of VA-ECMO support.
Novel strategies in antithrombotic therapy: targeting thrombosis while preserving hemostasis
Authors: Sim Martha M. S. , Shiferawe Semekidus , Wood Jeremy P.
Published: October 2023

Antithrombotic therapy is a delicate balance between the benefits of preventing a thrombotic event and the risks of inducing a major bleed. Traditional approaches have included antiplatelet and anticoagulant medications, require careful dosing and monitoring, and all carry some risk of bleeding. In recent years, several new targets have been identified, both in the platelet and coagulation systems, which may mitigate this bleeding risk. In this review, we briefly describe the current state of antithrombotic therapy, and then present a detailed discussion of the new generation of drugs that are being developed to target more safely existing or newly identified pathways, alongside the strategies to reverse direct oral anticoagulants, showcasing the breadth of approaches. Combined, these exciting advances in antithrombotic therapy bring us closer than we have ever been to the “holy grail” of the field, a treatment that separates the hemostatic and thrombotic systems, preventing clots without any concurrent bleeding risk.
Smooth muscle cells-specific loss of OCT4 accelerates neointima formation after acute vascular injury
Authors: Shin Junchul , Tkachenko Svyatoslav , Gomez Delphine , Tripathi Rupande , Owens Gary K. , Cherepanova Olga A.
Published: October 2023

Introduction

There is growing evidence that smooth muscle cell (SMC) phenotypic transitions play critical roles during normal developmental and tissue recovery processes and in pathological conditions such as atherosclerosis. However, the molecular mechanisms responsible for these transitions are not well understood. Recently, we found that the embryonic stem cell/induced pluripotent stem cell (iPSC) factor OCT4, which was believed to be silenced in somatic cells, plays an atheroprotective role in SMC, and regulates angiogenesis after corneal alkali burn and hindlimb ischemia by mediating microvascular SMC and pericyte migration. However, the kinetics of OCT4 activation in arterial SMC and its role in acute pathological conditions are still unknown.

Methods and Results

Here, using an Oct4-IRES-GFP reporter mouse model, we found that OCT4 is reactivated in the carotid artery 18 hours post-acute ligation-induced injury, a common in vivo model of the SMC phenotypic transitions. Next, using a tamoxifen-inducible Myh11-CreERT2 Oct4 knockout mouse model, we found that the loss of OCT4, specifically in SMC, led to accelerated neointima formation and increased tunica media following carotid artery ligation, at least in part by increasing SMC proliferation within the media. Bulk RNA sequencing analysis on the cultured SMC revealed significant down-regulation of the SMC contractile markers and dysregulation of the genes belonging to the regulation of cell proliferation and, positive and negative regulation for cell migration ontological groups following genetic inactivation of Oct4. We also found that loss of Oct4 resulted in suppression of contractile SMC markers after the injury and in cultured aortic SMC. Further mechanistic studies revealed that OCT4 regulates SMC contractile genes, ACTA2 and TAGLN, at least in part by direct binding to the promoters of these genes.

Conclusion

These results demonstrate that the pluripotency factor OCT4 is quickly activated in SMC after the acute vascular injury and inhibits SMC hyperproliferation, which may be protective in preventing excessive neointima formation.
Inhibition or promotion: the impact of carbon emission trading on market structure: evidence from China
Authors: Zhang Gong , Bi Shulei
Published: October 2023

Market structure serves as a crucial basis for government economic policies and the formulation of competitive strategies by businesses. It determines the formation of prices, the functioning of supply and demand relationships, the degree of competition, and exerts a significant influence on market economies. This paper first deduces the theoretical implications of carbon emissions trading on market structure and its regulating factors-based Theory of the Firm. It then utilizes the quasi-natural experiment of China’s pilot carbon emissions trading policy implemented in 2013, employing DID model, to empirically examine the policy effects and influencing mechanisms of carbon emissions trading on market structure. We find that carbon emissions trading policies can significantly inhibit market concentration and promote the development of market liberalization. This conclusion remains robust after a series of rigorous tests. Additionally, the analysis of dynamic effects reveals a noticeable lagged and incremental impact of carbon emissions trading policies on market structure. The negative adjustment of market concentration due to carbon emissions trading policies initiates in the policy’s starting year and gradually intensifies in the third phase. As expectations towards the policy stabilize, the negative adjustment decreases, and the short-term effects of carbon emissions trading policies are greater than the long-term effects. To verify the role of carbon emissions trading policies in influencing market structure during their implementation, a mechanism analysis based on cost and benefit perspectives is conducted. The results suggest that carbon emissions trading policies not only increase the environmental costs for industry-leading companies but also reduce the potential gains from market structure adjustments. Therefore, we propose promoting market competition, encouraging technological innovation, and strengthening transparency and regulation while considering differences in market structure. The findings of this paper provide new policy insights for promoting high-quality economic development and deepening market structure reforms in the context of the dual carbon goals.
Spatio-temporal relationship between carbon emission and ecosystem service value under land use change: a case study of the Guanzhong Plain Urban Agglomeration, China
Authors: Yang Shuo , Zheng Xiaozheng
Published: October 2023

Changes in land use restructuring significantly impact carbon emissions and the provision of ecosystem service value (ESV). This study focuses on the Guanzhong Plain Urban Agglomeration, and accounts for carbon emissions and ecosystem service values caused by land use in the years 2000, 2005, 2010, 2015, and 2020. Carbon sources, carbon sinks, net carbon emission intensity, and ESV intensity were introduced as research variables and the spatial and temporal divergence and correlation patterns between them were examined. The results show that: 1) The carbon emission intensity of land use in the Guanzhong Plain Urban Agglomeration has increased significantly over the study period, showing a distribution pattern of high intensity in the centra regions and low intensity in the surrounding regions. Construction land was identified as the largest carbon source. 2) The overall ESV follows an increasing trend, with the total value increasing from 215,263.7 million to 216,776.2 million. The distribution of ESV intensity is low in the central regions and high in the surrounding regions, and significant changes were observed in the ESV loss and gain intensity of farmland and water body. 3) Carbon emissions and ESV show a significant negative spatial correlation, and both are dominated by low-high and high-low aggregation patterns. A spatial spillover effect of carbon emissions on ESV was observed. Through the correlation analysis of carbon emissions and ESV, theoretical support is provided for promoting regional low-carbon green development and eco-economic synergistic development.
Validation of next-generation sequencing-based chimerism testing for accurate detection and monitoring of engraftment in hematopoietic stem cell transplantation
Authors: Kakodkar Pramath , Zhao Yayuan , Pan Henry , Wu Fang , Pearce Twyla , Webster Destinie , Elemary Mohamed , Sabry Waleed , Kwan Luvinia , Pelzer Lindsay , Bosch Mark , Sherwood Karen R. , Lan James , Tran Jenny , Liwski Robert , Keown Paul , Mostafa Ahmed
Published: October 2023

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a life-saving treatment for various hematological disorders. The success of allo-HSCT depends on the engraftment of donor cells and the elimination of recipient cells monitored through chimerism testing. We aimed to validate a next-generation sequencing (NGS)-based chimerism assay for engraftment monitoring and to emphasize the importance of including the most prevalent cell subsets in proficiency testing (PT) programs. We evaluated the analytical performance of NGS-based chimerism testing (AlloSeq-HCT and CareDx) with a panel of targeted 202 informative single-nucleotide polymorphisms (SNPs) (i.e., linearity and precision, analytical sensitivity and specificity, system accuracy, and reproducibility). We further compared the performance of our NGS panel with conventional short tandem repeat (STR) analysis in unfractionated whole blood and cell-subset-enriched CD3 and CD66. Our NGS-based chimerism monitoring assay has an impressive detection limit (0.3% host DNA) for minor alleles and analytical specificity (99.9%). Pearson’s correlation between NGS- and STR-based chimerism monitoring showed a linear relationship with a slope of 0.8 and r = 0.973. The concordance of allo-HSCT patients using unfractionated whole blood, CD3, and CD66 was 0.95, 0.96, and 0.54, respectively. Utilization of CD3+ cell subsets for mixed chimerism detection yielded an average of 7.3 ± 7-fold higher donor percentage detection compared to their corresponding unfractionated whole blood samples. The accuracy of the NGS assay achieved a concordance of 98.6% on blinded external quality control STR samples. The reproducibility series showed near 100% concordance with respect to inter-assay, inter-tech, inter-instrument, cell flow kits, and AlloSeq-HCT software versions. Our study provided robust validation of NGS-based chimerism testing for accurate detection and monitoring of engraftment in allo-HSCT patients. By incorporating the cell subsets (CD3 and CD66), the sensitivity and accuracy of engraftment monitoring are significantly improved, making them an essential component of any PT program. Furthermore, the implementation of NGS-based chimerism testing shows potential to streamline high-volume transplant services and improve clinical outcomes by enabling early relapse detection and guiding timely interventions.
Adalimumab biosimilar ABP 501 is equally effective and safe in long-term management of inflammatory bowel diseases patients when used as first biologic treatment or as replace of the ADA originator for a non-medical reason
Authors: Mocci Giammarco , Cingolani Arianna , Orrù Giorgia , Felice Carla , Onidi Francesca Maria , Lombardi Gianmarco , Checchin Davide , Colucci Raffaele , Grossi Laurino , Ferronato Antonio , Rocchi Chiara , Ascolani Marta , Satta Paolo Usai , Fanini Lucia , Pilati Stefano , Tursi Antonio
Published: October 2023

Objective

Biosimilars represent a new opportunity for inflammatory bowel disease (IBD) treatment and economic sustainability of therapies. This study aimed to evaluate the efficacy and long-term safety of the adalimumab biosimilar ABP 501 in biologic-naïve vs. biologic-switched IBD patients.

Methods

A retrospective observational study was conducted using a database of patients with IBD treated with ABP 501, biologic-naïve or switched from the original, at eight IBD centers. We included adult patients with at least one year of follow-up. The primary objective of this study was to assess the efficacy (persistence) and safety (adverse event rate) of ABP 501 therapy.

Results

A total of 118 patients with IBD were included in the analysis: 84 patients with Crohn’s disease (CD) (39 women, 45 men, mean age 40.4 ± 14.3 years; 33% biologic-naïve) and 34 patients with ulcerative Colitis (UC) (16 women, 18 men, mean age 38.9 ± 14.9 years; 61.8% biologic-naïve). Regarding the primary endpoint, no difference was observed in the efficacy between biologic-naïve patients and patients with Adalimumab (ADA) originator replacement for non-medical reasons in terms of long-term persistence. However, ABP 501 showed a higher percentage of sustained clinical remission at 2 years in patients with CD (64 patients, 77%) than in those with UC (15 patients, 45.5%; p=0.00091). Nine patients (six with CD and three with UC) experienced adverse events that led to drug discontinuation in three.

Conclusions

APB 501 showed a good safety and efficacy profile in maintaining clinical response at 2 years in patients with IBD, both as a treatment-naïve and as a replacement for ADA originator for non-medical reasons.