bluuebunny/crossref_metadata_2025 huggingface dataset:
The Phenomenon of Delaying Loss of Stability in the Theory of Singular Perturbations
Authors: Alybaev K. , Nurmatova M.
Published: December 2023

This paper considers an autonomous system of singularly perturbed equations of fast variables, consisting of four first-order equations and one equation of a slow variable. The first approximation matrix has pairwise complex conjugate eigenfunctions. The system has an equilibrium position, and the stability of the equilibrium position is lost at a certain value of the slow variable. At this point, the real parts of all eigenfunctions vanish. Early works considered cases when the stability of the equilibrium position is lost by one pair of complex conjugate eigenfunctions. The problem of the phenomenon of prolongation of the loss of stability of the equilibrium position has been solved.
European standards in the field of higher education and their implementation in Ukraine: challenges and opportunities
Authors: Lupak Zh. P.
Published: December 2023

The article analyzes the process of adaptation of European standards of higher education in Ukraine and considers the challenges and opportunities associated with their implementation. European and national standards of higher education are compared, the role and requirements for educational institutions and scientific and pedagogical workers are determined, the importance of improving the quality of education is considered.

The author of the article established that the implementation of European standards of higher education in Ukraine is an urgent task that creates opportunities for improving the quality of education and increasing the competitiveness of Ukrainian graduates on the international labor market. In addition, the implementation of European standards of higher education will contribute to the integration of Ukraine into the European educational space, which will lead to the development of scientific relationship and cooperation between the universities of Ukraine and the countries of the European Union. The article also analyzes issues related to the introduction of European standards in the field of higher education in Ukraine, which were partially studied by Ukrainian and foreign scientists. Thus, there are the opinions of a group of scientists who actively support the process of integration of the higher education system of Ukraine into the European space. Another group of scientists expresses some concern about the implementation of European standards and notes their negative impact on higher education in Ukraine. Therefore, this topic requires further research.

The author of the article cited the reasons that prevent the full implementation of European standards in higher education in Ukraine, including the Russian invasion of Ukraine, insufficient financial support of higher educational institutions, lack of sustainable motivation among scientific and pedagogical workers, bureaucratic obstacles and ineffectiveness of mechanisms for monitoring and evaluating the quality of education. For the successful integration of Ukrainian education into the European area of higher education, the author of the article proposed ways to solve these problems, which include, among other things, developing effective mechanisms for monitoring and evaluating the quality of education.

The conclusion of the article states that the introduction of European standards of higher education in Ukraine is an important step in the direction of reforming the system of higher education and bringing it in line with the requirements of the modern world.

Key words: European standards, higher education, culture of education quality, student-centered learning, tutor, autonomy of universities, challenges, opportunities, competitiveness.
Sentencing for treason under martial law
Authors: Miskiv T. I.
Published: December 2023

The article examines the issue of punishment for treason under martial law. It was found that in view of the full-scale invasion of Russia on the territory of Ukraine, the criminal legislation was supplemented by Part 2 of Art. 111 of the Criminal Code of Ukraine, which provides for responsibility for treason committed under martial law, and establishes a more severe punishment in the form of imprisonment for a term of 15 years or life imprisonment, with mandatory confiscation of property. 50 guilty verdicts passed by courts of first instance in criminal proceedings under Part 2 of Art. 111 of the Criminal Code of Ukraine. The results of such a study made it possible to determine some trends in the imposition of punishment for such a crime.

It has been established that treason under martial law is committed under similar legal circumstances, which can be generalized and classified. During the research, it was established that in the absolute majority of cases for the commission of treason, regardless of the circumstances of the crime, mitigating and aggravating circumstances, data about the accused person, the courts impose a minimum sentence of 15 years of imprisonment with full or partial confiscation of property. At the same time, the maximum punishment in the form of life imprisonment is imposed in isolated cases, which, however, raises doubts about the expediency and justification of its appointment. It is established that the courts when choosing the amount of punishment, as required by Art. 65 of the Criminal Code of Ukraine, take into account data on the identity of the culprit and circumstances mitigating and aggravating the punishment.

There were also cases of a milder punishment than provided for by the sanction of Part 2 of Article 111 of the Criminal Code of Ukraine, on the basis of Art. 69 of the Criminal Code of Ukraine. It is assumed that such cases of application of Art. 69 of the Criminal Code of Ukraine are not always justified and sometimes excessively reduce the punishment in comparison with the size of the punishment provided for in Part 2 of Art. 111 of the Criminal Code of Ukraine. The situation with the appointment of a minimum punishment within the scope of the sanction and the application of Art. 69 of the Criminal Code of Ukraine is explained by the imperfection of the sanction, which is difficult from the point of view of law enforcement. Based on the results of the analysis, the assumption was made that the sanction under Part 2 of Art. 111 of the Criminal Code of Ukraine, as well as suggested ways to solve this problem.

Key words: treason, national security of Ukraine, martial law, punishment, sentencing, life imprisonment, an absolutely defined sanction, transfer to the side of the enemy, subversion, aggressor state, differentiation of criminal responsibility, individualization of punishment, confiscation of property.
Indexation of pensions in Ukraine: mechanism and problematic issues
Authors: Khomych I. O.
Published: December 2023

The article carries out a scientific and practical study of the procedure for calculating pensions in the solidarity system of pension insurance in connection with the annual indexation in accordance with the Law of Ukraine «On Mandatory State Pension Insurance» dated 07/09/2003 No. 1058-IV. The definition of the concept of indexation of monetary incomes of the population is given. Changes in the legal regulation of indexation of pensions for the period from 2004 to 2023 are highlighted. Attention has been drawn to the fact that since 2004, two parallel pension indexation procedures have been provided for: the first is stipulated by the first part of Art. 42 of Law No. 1058- IV in accordance with the legislation on indexation of monetary incomes of the population, and the second – in accordance with the second part of Art. 42 of the said Law. From October 1, 2017, the first part of Art. 42 of the specified law is excluded, therefore, from this date, indexation of pensions is carried out only in accordance with part 2 of Art. 42 of the said Law. A comparison and analysis of pension calculation procedures in connection with indexation, approved by the Cabinet of Ministers of Ukraine in the editions that were in effect until February 2019 and after, was carried out. The reason why pensions assigned during the last three years preceding the year in which the pension is recalculated in connection with indexation has not been increased in recent years has been revealed. It was emphasized that the current pension indexation mechanism is unfair and discriminatory. It is proposed to bring the Procedure for indexation of pensions approved by the Cabinet of Ministers of Ukraine into compliance with the Law of Ukraine «On Mandatory State Pension Insurance», including the provision that pensions assigned based on applications received by December 31 inclusive, that precedes the year in which the recalculation is carried out, are subject to recalculation in connection with indexation, and excluding the reference to October 1, 2017 as the date on which the indicator of the average salary (income) in Ukraine was taken into account, from which insurance premiums were paid, and which is subject to an increase by the corresponding factor increase in indexation of pensions.

Key words: pension provision, mandatory state pension insurance, pension, indexation, pension recalculation, average wage index.
2002 TÜRKİYE GENEL SEÇİM AFİŞLERİNE YÖNELİK GÖSTERGEBİLİM ANALİZİ*
Authors: USLU Mehmet , YOLCU Tuğba
Published: December 2023

Siyaset, temsili demokrasinin ortaya çıkışı ile birlikte siyasi partiler arasındaki yarışa dönüşmüştür. Bu süreçte seçim kampanyaları özelikle kitle iletişim araçlarının ortaya çıkışı ile birlikte önemli bir alan haline gelmiştir. Seçim kampanyalarınla yüz yüze iletişimin dışında farklı araçlar kullanılmaktadır. Bunlardan biri de seçim afişleridir. Afişler verilmek istenen mesajın en kısa yoldan sunulmasına katkı sağlamaktadır. Afişlerde kullanılan ifadeler ya da sembollerde bulundukları dönemin izlerini görmek mümkündür. Çalışmada bu yaklaşımdan hareketle seçim dönemine ait siyasal ortamın ve partilerin ideolojik unsurlarının siyasi partiler tarafından kullanılan seçim afişlerine yansıması üzerine bir araştırma gerçekleştirilecektir. Bu amaçla 2022 yılı seçimlerinde kullanılan ve çalışma örnekleminde belirlenen afişler göstergebilim metodu çerçevesinde incelenmiştir. Çalışmada 2002 Genel Seçimlerine katılan siyasi partilerden Demokratik Sol Parti, Anavatan Partisi, Milliyetçi Hareket Partisi, 2002 Genel Seçimleri öncesinde koalisyon hükümetini oluşturan siyasi partiler olmaları sebebiyle, Adalet ve Kalkınma Partisi ise 2002 Genel Seçimlerini kazanan siyasi parti olması sebebiyle incelenen partiler olmuşlardır. Çalışma neticesinde, siyasal yapının, siyasi partiler tarafından seçim afişleri hazırlanırken dikkate alındığı ve ideolojik unsurların afişlerde kullanılan sloganlarla, görsellerle ve metinlerle önemli derecede bağlantılı olduğu sonucuna varılmıştır.
Edukasi Dan Pemeriksaan Boraks Dengan Bahan Alami Pada Jajanan Sekolah Menengah Atas
Authors: Mamay Mamay , Sulhan Muhammad Hadi , Ananda Riki
Published: December 2023

Borax is a food additive which is prohibited from being used in food. Toxic effects of borax have been found to be harmful to human health. This compound is still widely abused in food samples. Detection of the presence of borax in the sample can be done with the use of natural materials. This community service aims to provide education that can increase the understanding of high school student participants about the dangers of borax and the identification with natural indicator such as turmeric (Curcuma longa), azalea flowers (Rhododendron concina) and red soka flower (Ixora auminta). The method used in the form of counseling and training on borax detection in samples with test paper from turmeric extract, azalea flower extract and red soka flower extract. In the implementation of the service, it was found that there was a change in understanding of borax and its toxic effects from 58% to 96% of science class students and 27% to 87% of social studies students. In the borax examination training, 92% of science student participants and 88% of social studies students were able to perform an examination with natural ingredients using test paper of turmeric extract, azalea flower, red soka flower. From the service process, it was found that, most of the  participants knew about borax as a additive food which is prohibited from using and is harmful to health and can carry out a borax examination using natural indicators from turmeric, azalea flowers and red soka flowers.
New statue of Athena for the National Library of Greece
Authors: THEODOROU DESPOINA
Published: December 2023

A modern era statue of Athena is necessary at the premises of the new building of the National Library of Greece. While the aesthetics and functionality of the Renzo Piano-designed NLG building at SNFCC are undoubtedly excellent, visitors and employees at the Library will benefit from a new statue of Pallas Athena. This draft argues for this necessity, and discusses a number of decisions that have to be made by the modern sculptors who will create the new work of art.
Performing Nature’s Valuation: The art of natural capital accounting
Authors: Maechler Sylvain , Boisvert Valérie
Published: December 2023

Accounting for nature as capital is touted as a promising way of aligning environmental conservation with global capitalism by valuing nature like economic assets. Both its proponents and detractors speculate on what its promises might achieve if they were fully realized, i.e., if nature were actually accounted for, capitalized or commodified. There is, however, an enduring disjunction between vision and execution in this field: the promises simply do not materialize. Economizing nature proves to be extremely complex, raising not only technical hurdles but also intractable conceptual and ontological issues. We suggest taking a critical realist approach to natural capital accounting, acknowledging the inherent resistance of nature to being treated as capital. We consider the arenas dedicated to natural capital accounting as the sites of singular dramaturgical performances, whose effects extend beyond the integration of nature into economic decision making. Drawing on documents, interviews and observations at events dedicated to natural capital accounting, we highlight their theatrical character and reveal the effects they produce. This article aims to contribute to the investigation of environmental governance arenas by emphasizing their significance as venues for symbolic performance and achievement, extending beyond the traditional emphasis on regulatory and hoped-for environmental transformations.
An insight into recent developments of copper, silver and gold carbon dots: cancer diagnostics and treatment
Authors: Ullah Ihsan , Suliman Hazrat , Alamzeb Muhammad , Abid Obaid-Ur-Rahman , Sohail Muhammad , Ullah Mohib , Haleem Abdul , Omer Muhammad
Published: December 2023

Cancer is one of the most fatal diseases globally, however, advancement in the field of nanoscience specifically novel nanomaterials with nano-targeting of cancer cell lines has revolutionized cancer diagnosis and therapy and has thus attracted the attention of researchers of related fields. Carbon Dots (CDs)–C-based nanomaterials–have emerged as highly favorable candidates for simultaneous bioimaging and therapy during cancer nano-theranostics due to their exclusive innate FL and theranostic characteristics exhibited in different preclinical results. Recently, different transition metal-doped CDs have enhanced the effectiveness of CDs manifold in biomedical applications with minimum toxicity. The use of group-11 (Cu, Ag and Au) with CDs in this direction have recently gained the attention of researchers because of their encouraging results. This review summarizes the current developments of group-11 (Cu, Ag and Au) CDs for early diagnosis and therapy of cancer including their nanocomposites, nanohybrids and heterostructures etc. All The manuscript highlights imaging applications (FL, photoacoustic, MRI etc.) and therapeutic applications (phototherapy, photodynamic, multimodal etc.) of Cu-, Ag- and Au-doped CDs reported as nanotheranostic agents for cancer treatment. Sources of CDs and metals alogwith applications to give a comparative analysis have been given in the tabulated form at the end of manuscript. Further, future prospects and challenges have also been discussed.
Early in-hospital discontinuation of aspirin on the first post-procedural day after percutaneous coronary stent implantation in patients on direct oral anticoagulation
Authors: von Stein Philipp , Seitz Lukas , Wienemann Hendrik , Hohmann Christopher , Baar Till , Baldus Stephan , Halbach Marcel
Published: December 2023

Background

Previous trials investigating antithrombotic therapy with a direct oral anticoagulant (DOAC) and a P2Y12 inhibitor after percutaneous coronary intervention (PCI), termed dual therapy, allowed a short period of triple therapy including a DOAC, a P2Y12 inhibitor, and aspirin.

Aims

This study aimed to determine whether discontinuation of aspirin on the first post-procedural day is safe or causes ischemic events.

Methods

Ischemic and bleeding events during hospitalization were investigated retrospectively in all patients treated with dual therapy (DOAC + P2Y12 inhibitor, designated as group 1) or triple therapy (DOAC + P2Y12 inhibitor+aspirin, designated as group 2) from day 1 after PCI at our center.

Results

Of 4,564 consecutive PCI procedures, 1,059 (23.2%) had an indication for OAC. Of these, 322 met the inclusion criteria for group 1 and 62 for group 2. Baseline characteristics, CHA2DS2-VASc and HAS-BLED scores showed no relevant differences between the two groups, and the main indication for DOAC therapy was atrial fibrillation in both groups. Approximately ¼ of patients were treated for acute coronary syndrome. The mean length of post-procedural hospitalization was 2.1 ± 2.5 and 2.2 ± 3.0 days in group 1 and 2, respectively (p = 0.305). One patient per group suffered a TIA (p = 0.297). There were no other ischemic events and no statistically significant differences in bleeding events. A subgroup analysis of cases hospitalized for ≥2 post-procedural days (group 1: 100 cases, mean 4.4 ± 3.4 days vs. group 2: 25 cases, mean 4.0 ± 4.1 days) confirmed these results.

Conclusion

The initiation of dual therapy and thus discontinuation of aspirin on the first postprocedural day appears to be safe with respect to short-term ischemic events in a real-world population. Almost ¼ of patients undergoing PCI have an indication for OAC, highlighting the relevance of this issue.
Digital technologies for step counting: between promises of reliability and risks of reductionism
Authors: Angelucci Alessandra , Canali Stefano , Aliverti Andrea
Published: December 2023

Step counting is among the fundamental features of wearable technology, as it grounds several uses of wearables in biomedical research and clinical care, is at the center of emerging public health interventions and recommendations, and is gaining increasing scientific and political importance. This paper provides a perspective of step counting in wearable technology, identifying some limitations to the ways in which wearable technology measures steps and indicating caution in current uses of step counting as a proxy for physical activity. Based on an overview of the current state of the art of technologies and approaches to step counting in digital wearable technologies, we discuss limitations that are methodological as well as epistemic and ethical—limitations to the use of step counting as a basis to build scientific knowledge on physical activity (epistemic limitations) as well as limitations to the accessibility and representativity of these tools (ethical limitations). As such, using step counting as a proxy for physical activity should be considered a form of reductionism. This is not per se problematic, but there is a need for critical appreciation and awareness of the limitations of reductionistic approaches. Perspective research should focus on holistic approaches for better representation of physical activity levels and inclusivity of different user populations.
Safety of corticosteroid therapy in sarcoidosis treatment
Authors: Di Marco Berardino Alessandro , Mei Federico , Zuccatosta Lina
Published: December 2023

Introduction: Sarcoidosis is a multisystemic granulomatous disease of unknown origin and unpredictable cause, characterized by a dysregulated immune response. If histopathological hallmark is represented by the presence of non-caseating granulomas, clinical manifestations are variable and symptoms are not specific, and they depend on organs affected. Although thoracic involvement (lung and mediastinum) is the most common clinical manifestation, any organ can be virtually affected.

Methods: This paper is structured as a narrative review. A literature search was performed in four electronic databases (Pubmed, Cochrane, Scopus, and Ovid Medline) and Google from inception until February 2023 for relevant studies, meta-analyses, and reviews on corticosteroids’ adverse events in sarcoidosis. English language only papers were included.

Discussion: Although antimetabolites (such as Methotrexate) and immunosuppressant agents can be used as alternative therapy in refractory cases, traditionally systemic glucocorticoids represent the first choice for sarcoidosis treatment. However, their use is still debated, due to potential adverse effects, leading to a wide spectrum of complications particularly in patients who required long-term therapy. Hence, this article aims to provide a comprehensive updated review on the safety profile of glucocorticoid treatment in patients with sarcoidosis and their systemic effects.

Conclusion: corticosteroids remain the first choice in Sarcoidosis, however, due to numerous side effects, dose and duration of treatment should be carefully adjusted and monitored by clinicians.
Association between serum total bilirubin and diabetic kidney disease in US diabetic patients
Authors: Lv Jian-Min , Shi Xiu-E , Ma Qiong , Chen Nan , Fu Mi , Liu Jian-Zheng , Fan Qiao-Rong
Published: December 2023

Background

Bilirubin has been widely reported to be a protective factor against diabetic kidney disease (DKD) in Asian populations. However, few large-sample analyses have been conducted in American populations. This study aimed to investigate the association between serum total bilirubin (STB) level and DKD in a US diabetic cohort.

Methods

This cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (NHANES) 2003–2018. Univariate and multivariate logistic regression analyses were performed to assess the association between STB level and DKD. Three models were conducted to control the potential confounding factors. Subgroup analysis was carried out for further validation.

Results

Among the 5,355 participants, the median age [interquartile range (IQR)] was 62 [52–71] years; 2,836 (52.96%) were male, and 1,576 (29.43%) were diagnosed with DKD. In the entire cohort, no significant association between STB level and DKD was observed in any logistic regression models (p > 0.05). Subgroup analysis revealed that, in U.S. diabetic males, STB levels > 11.98 µmol/L were associated with a nearly 30% lower risk of DKD than STB levels ≤ 8.55 µmol/L. Additionally, a moderate STB level (8.56–11.98 μmol/L) was found associated with a nearly 25% lower risk of DKD in U.S. diabetic patients over 65 years old.

Conclusion

The association of STB level with DKD may depict differences across diverse populations, among which the impact of race, sex, and age requires thorough consideration and relevant inferences should be interpreted cautiously.
Defining priorities for wildfire mitigation actions at the local scale: insights from a novel risk analysis method applied in Portugal
Authors: Benali Akli , Aparício Bruno A. , Gonçalves Ana , Oliveira Sandra
Published: December 2023

Introduction

In Portugal, the 2017 fire season was particularly extreme, leading to an unprecedented large number of fatalities, injured people, destruction of houses and infrastructures. These dramatic outcomes have contributed to raise awareness regarding the importance of ensuring the safety of people and assets from high intensity uncontrollable wildfires. It is crucial to identify the settlements at higher risk and the most suitable mitigation actions that can maximize the protection of people and assets.

Methods

We developed a simple methodology that combines exposure and vulnerability to estimate wildfire risk at the local level. Exposure was estimated using a fire spread simulation approach that was used to determine the probability of (i) a wildfire generating firebrands that could affect a settlement and (ii) a high intensity wildfire occurring adjacent to a settlement. Exposure was estimated using two fuel scenarios created to represent the current year of 2023 (short-term scenario) and 2030, assuming that no fuel management nor large fires occur in the meantime (medium-term worst-case scenario). Vulnerability was determined by the (i) Index of Total Dependence (IDT), and (ii) evacuation difficulty. Exposure and vulnerability metrics were normalized in percentiles, distributed into quadrants and combined to provide six levels of wildfire risk. For each vulnerability\exposure combination, we proposed a set of priority mitigation actions. The methodology was applied to three areas in Portugal where the risk estimates were analyzed and compared with the implementation rate of two risk mitigation programs already in place.

Results

Results showed that 8.7% of the settlements had “very high” wildfire risk and about 19.5% had “high” wildfire risk, potentially affecting 8,403 and 34,762 inhabitants, respectively. The spatial distribution of settlements at higher risk was very heterogeneous across the study areas and the total fraction ranged between 14% in Coimbra to 36% in Barlavento Algarvio. The overall implementation of mitigation programs in the study areas is very low, with only around 1% of the settlements in “very high” risk having any of the mitigation programs implemented. Conversely, our results also suggest that the implementation rate in settlements classified in lower risk classes is disproportionately high.

Discussion

The application of this risk analysis methodology can be used to assess the implementation status of mitigation actions, and contribute to tailor the actions that maximize the protection of people and assets according to the specific conditions found in each targeted area.
Cladribine and ocrelizumab induce differential miRNA profiles in peripheral blood mononucleated cells from relapsing–remitting multiple sclerosis patients
Authors: Arisi Ivan , Malimpensa Leonardo , Manzini Valeria , Brandi Rossella , Gosetti di Sturmeck Tommaso , D’Amelio Chiara , Crisafulli Sebastiano , Ferrazzano Gina , Belvisi Daniele , Malerba Francesca , Florio Rita , Pascale Esterina , Soreq Hermona , Salvetti Marco , Cattaneo Antonino , D’Onofrio Mara , Conte Antonella
Published: December 2023

Background and objectives

Multiple sclerosis (MS) is a chronic, progressive neurological disease characterized by early-stage neuroinflammation, neurodegeneration, and demyelination that involves a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. Even though several disease-modifying therapies (DMTs) are available to prevent MS-related brain damage—acting on the peripheral immune system with an indirect effect on MS lesions—individualizing therapy according to disease characteristics and prognostic factors is still an unmet need. Given that deregulated miRNAs have been proposed as diagnostic tools in neurodegenerative/neuroinflammatory diseases such as MS, we aimed to explore miRNA profiles as potential classifiers of the relapsing–remitting MS (RRMS) patients’ prospects to gain a more effective DMT choice and achieve a preferential drug response.

Methods

A total of 25 adult patients with RRMS were enrolled in a cohort study, according to the latest McDonald criteria before (pre-cladribine, pre-CLA; pre-ocrelizumab, pre-OCRE, time T0) and after high-efficacy DMTs, time T1, 6 months post-CLA (n = 10, 7 F and 3 M, age 39.0 ± 7.5) or post-OCRE (n = 15, 10 F and 5 M, age 40.5 ± 10.4) treatment. A total of 15 age- and sex-matched healthy control subjects (9 F and 6 M, age 36.3 ± 3.0) were also selected. By using Agilent microarrays, we analyzed miRNA profiles from peripheral blood mononuclear cells (PBMC). miRNA–target networks were obtained by miRTargetLink, and Pearson’s correlation served to estimate the association between miRNAs and outcome clinical features.

Results

First, the miRNA profiles of pre-CLA or pre-OCRE RRMS patients compared to healthy controls identified modulated miRNA patterns (40 and seven miRNAs, respectively). A direct comparison of the two pre-treatment groups at T0 and T1 revealed more pro-inflammatory patterns in the pre-CLA miRNA profiles. Moreover, both DMTs emerged as being capable of reverting some dysregulated miRNAs toward a protective phenotype. Both drug-dependent miRNA profiles and specific miRNAs, such as miR-199a-3p, miR-29b-3p, and miR-151a-3p, emerged as potentially involved in these drug-induced mechanisms. This enabled the selection of miRNAs correlated to clinical features and the related miRNA–mRNA network.

Discussion

These data support the hypothesis of specific deregulated miRNAs as putative biomarkers in RRMS patients’ stratification and DMT drug response.
Construction of a ferroptosis-based prognostic model for breast cancer helps to discriminate high/low risk groups and treatment priority
Authors: Zhang Liyong , Zhao Tingting , Wu Xiujuan , Tian Hao , Gao Pingping , Chen Qingqiu , Chen Ceshi , Zhang Yi , Wang Shushu , Qi Xiaowei , Sun Na
Published: December 2023

Introduction

Breast cancer is a common malignant tumor associated with high morbidity and mortality. The role of ferroptosis, a regulated form of cell death, in breast cancer development and prognosis remains unclear. This study aims to investigate the relationship between ferroptosis-related genes and breast cancer and develop a prognostic model.

Methods

RNA-seq expression datasets and clinical samples of breast cancer patients were obtained from public databases. Immunity- and drug resistance-related data were integrated. A preliminary screening was performed, resulting in the identification of 73 candidate ferroptosis factors. Univariate Cox regression analysis was conducted to select 12 genes, followed by LASSO Cox regression analysis to construct a prognostic risk prediction model consisting of 10 ferroptosis-related genes. The model was further characterized by immune cell infiltration. The expression levels of ferroptosis-related genes were validated in human breast cancer cell lines, and immunohistochemical (IHC) analysis was conducted on cancer specimens to assess ferroptosis-related protein expression.

Results:

The study identified 10 ferroptosis-related genes that were significantly associated with breast cancer prognosis. The constructed prognostic risk prediction model showed potential for predicting the prognostic value of these genes. In addition, the infiltration of immune cells was observed to be a characteristic of the model. The expression levels of ferroptosis-related genes were confirmed in human breast cancer cell lines, and IHC analysis provided evidence of ferroptosis-related protein expression in cancer specimens.

Discussion

This study provides a novel prognostic model for breast cancer, incorporating 10 ferroptosis-related genes. The model demonstrates the potential for predicting breast cancer prognosis and highlights the involvement of immune cell infiltration. The expression levels of ferroptosis-related genes and proteins further support the association between ferroptosis and breast cancer development.
Comprehensive analysis of mitophagy-related genes in NSCLC diagnosis and immune scenery: based on bulk and single-cell RNA sequencing data
Authors: Yu Haibo , Liu Qingtao , Jin Mingming , Huang Gang , Cai Qianqian
Published: December 2023

Lung cancer is the main cause of cancer-related deaths, and non-small cell lung cancer (NSCLC) is the most common type. Understanding the potential mechanisms, prognosis, and treatment aspects of NSCLC is essential. This study systematically analyzed the correlation between mitophagy and NSCLC. Six mitophagy-related feature genes (SRC, UBB, PINK1, FUNDC1, MAP1LC3B, and CSNK2A1) were selected through machine learning and used to construct a diagnostic model for NSCLC. These feature genes are closely associated with the occurrence and development of NSCLC. Additionally, NSCLC was divided into two subtypes using unsupervised consensus clustering, and their differences in clinical characteristics, immune infiltration, and immunotherapy were systematically analyzed. Furthermore, the interaction between mitophagy-related genes (MRGs) and immune cells was analyzed using single-cell sequencing data. The findings of this study will contribute to the development of potential diagnostic biomarkers for NSCLC and the advancement of personalized treatment strategies.
Emerging strategy towards mucosal healing in inflammatory bowel disease: what the future holds?
Authors: Wang Min , Shi Jingyan , Yu Chao , Zhang Xinyi , Xu Gaoxin , Xu Ziyan , Ma Yong
Published: December 2023

For decades, the therapeutic goal of conventional treatment among inflammatory bowel disease (IBD) patients is alleviating exacerbations in acute phase, maintaining remission, reducing recurrence, preventing complications, and increasing quality of life. However, the persistent mucosal/submucosal inflammation tends to cause irreversible changes in the intestinal structure, which can barely be redressed by conventional treatment. In the late 1990s, monoclonal biologics, mainly anti-TNF (tumor necrosis factor) drugs, were proven significantly helpful in inhibiting mucosal inflammation and improving prognosis in clinical trials. Meanwhile, mucosal healing (MH), as a key endoscopic and histological measurement closely associated with the severity of symptoms, has been proposed as primary outcome measures. With deeper comprehension of the mucosal microenvironment, stem cell niche, and underlying mucosal repair mechanisms, diverse potential strategies apart from monoclonal antibodies have been arising or undergoing clinical trials. Herein, we elucidate key steps or targets during the course of MH and review some promising treatment strategies capable of promoting MH in IBD.
Complete and early response to cemiplimab associated to severe immune toxicity in advanced cervical cancer: a case report
Authors: Passarelli Anna , Pisano Carmela , Coppola Elisabetta , Ventriglia Jole , Cecere Sabrina Chiara , Di Napoli Marilena , Carideo Luciano , Lastoria Secondo , Pignata Sandro
Published: December 2023

Cervical cancer (CC) is the second most commonly diagnosed cancer and the third leading cause of cancer death among females. The options of treatment for recurrent/advanced CC are limited and patients experiencing recurrence after first line platinum-based chemotherapy have a poor prognosis. In this context, immune checkpoint inhibitors (ICI)s antagonizing PD-1 and programmed death-ligand 1 (PD-L1) have profoundly changed the treatment scenario and outcomes in CC in the first or subsequent lines both as monotherapies or in combination with chemotherapy or other ICIs. Herein, we report the clinical case of a 74-year-old woman with metastatic CC with negative tumor PD-L1 expression who having disease progression after first-line of systemic treatment with platinum, thus undergoing to anti-PD-1 namely cemiplimab. The patient achieved a surprising, fast and complete metabolic response to cemiplimab immediately discontinued after only two cycles due to the onset of rare and severe immune-related adverse events (irAE)s such cardiovascular toxicity and hypertransaminasemia. Despite this, thirteen months later, the patient remains disease-free despite cemiplimab was withdrawn.
Fabrication and surface characterization of titanium dioxide nanotubes on titanium implants
Authors: Zheng Hongming , Xu Li , Jiao Yang , Xia Yan , Wu Xinglin , Lu Kaihang , Zhang Pengpeng , Zhao Quanming , Zhang Lu , Ni Xiaohui
Published: December 2023

Titanium has been widely used in orthopedics and dental implants due to its excellent biocompatibility and mechanical properties. However, the surface of titanium is biologically inert and lacks biological activity, resulting in poor integration between titanium-based implants and surrounding natural bone tissue, which is a common challenge in its clinical application. Surface modification is currently an effective means to improve the biocompatibility and bioactivity of titanium implants. The natural tissues of the human body are assembled from nanomodules, so from a biomimetic perspective, nanostructures should have better biological activity. TiO2 nanotubes have unique physical and chemical properties due to their elastic modulus, large specific surface area, and regular hollow structure similar to those of bone tissue. This study used anodic oxidation technology to prepare TiO2 nanotubes on the surface of titanium. The surface properties of the nanotubes were evaluated using field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), atomic force microscopy profilometry, contact angle measurements, etc. The corrosion resistance was tested using an electrochemical workstation. The results indicate that anodic oxidation can be used to successfully prepare titanium dioxide nanotube arrays on the surface of titanium. The nanotubes not only exhibit a good structure but also improve the surface hydrophilicity and corrosion resistance of titanium, thereby demonstrating potential for clinical application.
Perceptions and experiences of community-based healthcare professionals in the state of Qatar having do not attempt resuscitation discussions during the COVID-19 pandemic
Authors: Fitzgerald Audrey , Fitzgerald Conor , Anderson Louise , Hussain Ammar Ali , Alinier Guillaume
Published: December 2023

Introduction

The values and attitudes of healthcare professionals influence their handling of “do-not-attempt-resuscitation” (DNAR) orders, as does that of the families they interact with. The aim of this study was to describe attitudes, perceptions, and practices among community-based medical practitioners towards discussing cardiopulmonary resuscitation and DNAR orders with patients and their relatives, and to investigate if the COVID-19 pandemic affected their practice in having these discussions.

Methods

This is a researcher-developed online survey-based study which aimed to recruit a convenience sample of respondents from a total population of 106 healthcare professionals working for the Mobile Healthcare Service (MHS), Hamad Medical Corporation Ambulance Service in the State of Qatar.

Results

33 family physicians, 38 nurses, and 20 paramedics (n = 91) responded to the questionnaire, of who around 40, 8, and 50%, respectively, had engaged in Do Not Attempt Resuscitation discussions during their work with MHS. 15% of physicians who had experience with Do Not Attempt Resuscitation discussions in Qatar felt that the family or patient were not open to having such discussions. 90% of paramedics thought that Do Not Attempt Resuscitation was a taboo topic for their patients in Qatar, and this view was shared by 75% of physicians and 50% of nurses. Per the responses, the COVID-19 pandemic had not affected the likelihood of most of the physicians or nurses (and 50% of the paramedics) identifying patients with whom having a Do Not Attempt Resuscitation discussion would be clinically appropriate.

Discussion

Overall, for all three groups, the COVID-19 pandemic did not affect the likelihood of identifying patients with whom a Do Not Attempt Resuscitation discussion would be clinically appropriate. We found that the greatest barriers in having Do Not Attempt Resuscitation discussions were perceived to be the religious or cultural beliefs of the patient and/or their family, along with the factor of feeling the staff member did not know the patient or their family well enough. All three groups said they would be more likely to have a conversation about Do Not Attempt Resuscitation if barriers were addressed.
Therapeutic effects of curcumin on constipation-predominant irritable bowel syndrome is associated with modulating gut microbiota and neurotransmitters
Authors: Tu Xiaoting , Ren Hongyan , Bu Shurui
Published: December 2023

Introduction

Constipation-predominant irritable bowel syndrome (IBS-C) is a functional bowel disease that affects 10–20% of the population worldwide. Curcumin (CUR) is widely used in traditional Chinese medicine to treat IBS, but its mechanism of action needs further investigation.

Methods

In this study, we used mosapride (MOS) as a positive control to evaluate the changes in gut microbiota in IBS-C rat models after treatment with CUR or MOS by analyzing 16S rDNA variation. In addition, we used enzyme immunoassay kits and immunohistochemical analysis to investigate whether CUR or MOS influenced serotonin (5-HT), substance P (SP), and vasoactive intestinal peptide (VIP) levels in the serum and colon of IBS-C rats.

Results

The study showed that rats supplemented with CUR showed significantly increased fecal weight, fecal water content, small intestine transit rate and significantly decreased serum levels of 5-HT, VIP and SP compared to the IBS group (p < 0.05). In addition, treatment with CUR changed the relative abundance of Blautia, Sutterella, Acetanaerobacterium and Ruminococcus2 in the gut microbiota.

Discussion

This study showed that the efficacy of CUR on IBS-C was possibly by modulating the microbiota and lowering the serum levels of HT, SP, and VIP.
Yield components affected by rice black-streaked dwarf virus disease in rice cultivars with different resistance levels
Authors: Sun Yue , Jing Dedao , Zhang Jiayuan , Du Linlin , Li Chenyang , Lan Ying , Lin Feng , Zhou Tong
Published: December 2023

Introduction

Rice black-streaked dwarf virus disease (RBSDVD) is one of the most destructive rice viral diseases, leading to severe yield losses in rice production. However, little is known about the yield-related components associated with the disease and no resistance cultivars have been successfully used in rice breeding.

Methods

Seven rice cultivars were analyzed in this study, including six commercial rice varieties and a new line Zhongjian No. 201 (ZJ201) containing the resistance gene OsAP47. Resistance levels of these cultivars were evaluated by artificial inoculation and yield components were collected, including panicle length (PL), spikelets per panicle (SPP), ripened grains per panicle (RGPP), as well as panicles per square meter (PPSM) and 1000-grain weight (TGW). Seed setting rate (SSR) were calculated with the data of SPP and RGPP.

Results and discussion

The results showed that ZJ201 displayed the highest resistance level and most of the commercial rice cultivars exhibited susceptible to RBSDVD. Yields of all the rice cultivars were significantly declined except ZJ201 and yield losses produced by RBSDVD were mainly due to the reduction of PL, SPP, RGPP, and TGW, suggesting that developments of these traits are associated with RBSDV infection. Resistant rice cultivar could reduce yield losses by maintaining normal development of these traits. Significant correlations were identified between resistance levels and the yield components except SSR and PPSM. The results provided useful clues for understanding the mechanisms of RBSDV invasion and its effect on rice production. ZJ201 was demonstrated as a resistance material that could be used in rice breeding.
Promoter DNA recognition by the Enterococcus faecalis global regulator MafR
Authors: Moreno-Blanco Ana , Pluta Radoslaw , Espinosa Manuel , Ruiz-Cruz Sofía , Bravo Alicia
Published: December 2023

When Enterococcus faecalis is exposed to changing environmental conditions, the expression of many genes is regulated at the transcriptional level. We reported previously that the enterococcal MafR protein causes genome-wide changes in the transcriptome. Here we show that MafR activates directly the transcription of the OG1RF_10478 gene, which encodes a hypothetical protein of 111 amino acid residues. We have identified the P10478 promoter and demonstrated that MafR enhances the efficiency of this promoter by binding to a DNA site that contains the −35 element. Moreover, our analysis of the OG1RF_10478 protein AlphaFold model indicates high similarity to 1) structures of EIIB components of the bacterial phosphoenolpyruvate:carbohydrate phosphotransferase system, and 2) structures of receiver domains that are found in response regulators of two-component signal transduction systems. However, unlike typical EIIB components, OG1RF_10478 lacks a Cys or His residue at the conserved phosphorylation site, and, unlike typical receiver domains, OG1RF_10478 lacks a conserved Asp residue at the position usually required for phosphorylation. Different from EIIB components and receiver domains, OG1RF_10478 contains an insertion between residues 10 and 30 that, according to ColabFold prediction, may serve as a dimerization interface. We propose that OG1RF_10478 could participate in regulatory functions by protein-protein interactions.
Effect of neuromuscular electrical stimulation therapy using the StimaWELL 120MTRS system on erector spinae morphology in patients with chronic low back pain
Authors: Balthazard Loïck , Wolfe Daniel , Fortin Maryse
Published: December 2023

Objective

Chronic low-back pain (CLBP) is the leading cause of disability globally. CLBP is associated with a decrease in cross-sectional area (CSA) and an increase in fat infiltration (FI) of the lumbar paraspinal muscles, such as erector spinae (ES). Neuromuscular electrical stimulation (NMES) therapy showed promising outcomes in the treatment of CLBP, but its impact on ES morphology is unknown. Therefore, this study aimed to compare the effect of two NMES protocols on ES CSA and FI in a cohort of patients with CLBP.

Methods

Twenty participants with CLBP (aged 18–60 years old) were randomized into the phasic (n = 11) or the combined (n = 9) protocol groups. They completed a 10-week (20 sessions) NMES therapy using the StimaWELL 120MTRS device. Magnetic resonance imaging (MRI) examinations were acquired at baseline and post-intervention to assess ES CSA and FI at all spinal levels (e.g., L1–L2 to L5–S1). Statistical analyses were conducted to assess the effect of the intervention on ES morphology irrespective of groups, and between groups.

Results

Irrespective of groups, participants showed a decrease in left ES CSA (p = 0.005) at L2–L3 and left ES FI at L5–S1 (p = 0.040). We also observed a greater decrease in ES FI in the combined protocol compared to the phasic protocol on the right side at L3–L4 (p = 0.029) and L4–L5 (p = 0.015). No other changes in ES CSA or FI were observed (p > 0.05).

Conclusion

NMES therapy demonstrated minimal effect on ES morphology in patients with CLBP. Further research is needed to extend and confirm our findings.