bluuebunny/crossref_metadata_2025 huggingface dataset:
CD19-immunoPET for noninvasive visualization of CD19 expression in B-cell lymphoma patients
Authors: Sonanini Dominik , Schwenck Johannes , Blaess Simone , Schmitt Julia , Maurer Andreas , Ehrlichmann Walter , Ritter Malte , Skokowa Julia , Kneilling Manfred , Jung Gundram , Fend Falko , Krost Simon , Seitz Christian M. , Lang Peter , Reischl Gerald , Handgretinger Rupert , Fougère Christian la , Pichler Bernd J.
Published: May 2024

Cell- and antibody-based CD19-directed therapies have demonstrated great potential for treating B-cell non-Hodgkin lymphoma (B-NHL). However, all these approaches suffer from limited response rates and considerable toxicity. Until now, therapy decisions have been routinely based on histopathological CD19 staining of a single lesion at initial diagnosis or relapse, disregarding heterogeneity and temporal alterations in antigen expression. To visualize in vivo CD19 expression noninvasively, we radiolabeled anti-human CD19 monoclonal antibodies with copper-64 (64Cu-αCD19) for positron emission tomography (CD19-immunoPET). 64Cu-αCD19 specifically bound to subcutaneous Daudi xenograft mouse models in vivo. Importantly, 64Cu-αCD19 did not affect the anti-lymphoma cytotoxicity of CD19 CAR-T cells in vitro. Following our preclinical validation, 64Cu-αCD19 was injected into four patients with follicular lymphoma, diffuse large B-cell lymphoma or mantle zone lymphoma. We observed varying 64Cu-αCD19 PET uptake patterns at different lymphoma sites, both within and among patients, correlating with ex vivo immunohistochemical CD19 expression. Moreover, one patient exhibited enhanced uptake in the spleen compared to that in patients with prior B-cell-depleting therapy, indicating that 64Cu-αCD19 is applicable for identifying B-cell-rich organs. In conclusion, we demonstrated the specific targeting and visualization of CD19+ B-NHL in mice and humans by CD19-immunoPET. The intra- and interindividual heterogeneous 64Cu-αCD19 uptake patterns of lymphoma lesions indicate variability in CD19 expression, suggesting the potential of CD19-immunoPET as a novel tool to guide CD19-directed therapies.
Web-based diagnostic platform for microorganism-induced deterioration on paper-based cultural relics with iterative training from human feedback
Authors: Liu Chenshu , Ben Songbin , Liu Chongwen , Li Xianchao , Meng Qingxia , Hao Yilin , Jiao Qian , Yang Pinyi
Published: May 2024

Purpose

Paper-based artifacts hold significant cultural and social values. However, paper is intrinsically fragile to microorganisms, such as mold, due to its cellulose composition, which can serve as a microorganisms’ nutrient source. Mold not only can damage papers’ structural integrity and pose significant challenges to conservation works but also may subject individuals attending the contaminated artifacts to health risks. Current approaches for strain identification usually require extensive training, prolonged time for analysis, expensive operation costs, and higher risks of secondary damage due to sampling. Thus, in current conservation practices with mold-contaminated artifacts, little pre-screening or strain identification was performed before mold removal, and the cleaning techniques are usually broad-spectrum rather than strain-specific. With deep learning showing promising applications across various domains, this study investigated the feasibility of using a convolutional neural network (CNN) for fast in-situ recognition and classification of mold on paper.

Methods

Molds were first non-invasively sampled from ancient Xuan Paper-based Chinese books from the Qing and Ming dynasties. Strains were identified using molecular biology methods and the four most prevalent strains were inoculated on Xuan paper to create mockups for image collection. Microscopic images of the molds as well as their stains situated on paper were collected using a compound microscope and commercial microscope lens for cell phone cameras, which were then used for training CNN models with a transfer learning scheme to perform the classification of mold. To enable involvement and contribution from the research community, a web interface that actuates the process while providing interactive features for users to learn about the information of the classified strain was constructed. Moreover, a feedback functionality in the web interface was embedded for catching potential classification errors, adding additional training images, or introducing new strains, all to refine the generalizability and robustness of the model.

Results & Conclusion

In the study, we have constructed a suite of high-confidence classification CNN models for the diagnostic process for mold contamination in conservation. At the same time, a web interface was constructed that allows recurrently refining the model with human feedback through engaging the research community. Overall, the proposed framework opens new avenues for effective and timely identification of mold, thus enabling proactive and targeted mold remediation strategies in conservation.
Evolution of worldwide geothermal power 2020–2023
Authors: Gutiérrez-Negrín Luis C. A.
Published: May 2024

Only 32 countries in the world have geothermal power plants in operation, with a combined capacity of 16,318 MW installed in 198 geothermal fields with 673 individual power units. Almost 37% of those units are of flash type with a combined capacity of 8598 MW (52.7% of total), followed by binary ORC type units with 25.1% of the installed capacity. The select list of geothermal power countries continues to be headed by the US, followed by Indonesia, the Philippines and Türkiye, and generated 96,552 GWh of electricity, at an average annual capacity factor of 67.5%, which represented 0.34% of the worldwide electric generation. Electricity from geothermal origin represented more than 10% of the total generated in at least seven countries, headed by Kenya, Iceland, and El Salvador. Practically, all geothermal fields in operation are harnessing resources from hydrothermal, conventional reservoirs, through an estimate of 3700 production wells at an annual average production of almost 3 MWh per well. Things could be similar in the next few years if the current trend continues, but all can change due to the world urgency to maintain global warming below the 1.5 °C threshold in the following years.
Scanning the active center of formolase to identify key residues for enhanced C1 to C3 bioconversion
Authors: Cheng Guimin , Sun Hongbing , Wang Qian , Yang Jinxing , Qiao Jing , Zhong Cheng , Cai Tao , Wang Yu
Published: May 2024

Background

Formolase (FLS) is a computationally designed enzyme that catalyzes the carboligation of two or three C1 formaldehyde molecules into C2 glycolaldehyde or C3 dihydroxyacetone (DHA). FLS lays the foundation for several artificial carbon fixation and valorization pathways, such as the artificial starch anabolic pathway. However, the application of FLS is limited by its low catalytic activity and product promiscuity.

Findings

FLS, designed and engineered based on benzoylformate decarboxylase from Pseudomonas putida, was selected as a candidate for modification. To evaluate its catalytic activity, 25 residues located within an 8 Å distance from the active center were screened using single-point saturation mutagenesis. A screening approach based on the color reaction of the DHA product was applied to identify the desired FLS variants. After screening approximately 5,000 variants (approximately 200 transformants per site), several amino acid sites that were not identified by directed evolution were found to improve DHA formation. The serine-to-phenylalanine substitution at position 236 improved the activity towards DHA formation by 7.6-fold. Molecular dynamics simulations suggested that the mutation increased local hydrophobicity at the active site, predisposing the cofactor-C2 intermediate to nucleophilic attack by the third formaldehyde molecule for subsequent DHA generation.

Conclusions

This study provides improved FLS variants and valuable information into the influence of residues adjacent to the active center affecting catalytic efficiency, which can guide the rational engineering or directed evolution of FLS to optimize its performance in artificial carbon fixation and valorization.
Combined transcriptomics and proteomics unveil the impact of vitamin C in modulating specific protein abundance in the mouse liver
Authors: Aumailley Lucie , Bodein Antoine , Adjibade Pauline , Leclercq Mickaël , Bourassa Sylvie , Droit Arnaud , Mazroui Rachid , Lebel Michel
Published: May 2024

Background

Vitamin C (ascorbate) is a water-soluble antioxidant and an important cofactor for various biosynthetic and regulatory enzymes. Mice can synthesize vitamin C thanks to the key enzyme gulonolactone oxidase (Gulo) unlike humans. In the current investigation, we usedGulo−/−mice, which cannot synthesize their own ascorbate to determine the impact of this vitamin on both the transcriptomics and proteomics profiles in the whole liver. The study includedGulo−/−mouse groups treated with either sub-optimal or optimal ascorbate concentrations in drinking water. Liver tissues of females and males were collected at the age of four months and divided for transcriptomics and proteomics analysis. Immunoblotting, quantitative RT-PCR, and polysome profiling experiments were also conducted to complement our combined omics studies.

Results

Principal component analyses revealed distinctive differences in the mRNA and protein profiles as a function of sex between all the mouse cohorts. Despite such sexual dimorphism, Spearman analyses of transcriptomics data from females and males revealed correlations of hepatic ascorbate levels with transcripts encoding a wide array of biological processes involved in glucose and lipid metabolisms as well as in the acute-phase immune response. Moreover, integration of the proteomics data showed that ascorbate modulates the abundance of various enzymes involved in lipid, xenobiotic, organic acid, acetyl-CoA, and steroid metabolism mainly at the transcriptional level, especially in females. However, several proteins of the mitochondrial complex III significantly correlated with ascorbate concentrations in both males and females unlike their corresponding transcripts. Finally, poly(ribo)some profiling did not reveal significant enrichment difference for these mitochondrial complex III mRNAs betweenGulo−/−mice treated with sub-optimal and optimal ascorbate levels.

Conclusions

Thus, the abundance of several subunits of the mitochondrial complex III are regulated by ascorbate at the post-transcriptional levels. Our extensive omics analyses provide a novel resource of altered gene expression patterns at the transcriptional and post-transcriptional levels under ascorbate deficiency.
Attention capture by own name decreases with speech compression
Authors: Li Simon Y. W. , Lee Alan L. F. , Chiu Jenny W. S. , Loeb Robert G. , Sanderson Penelope M.
Published: May 2024

Auditory stimuli that are relevant to a listener have the potential to capture focal attention even when unattended, the listener’s own name being a particularly effective stimulus. We report two experiments to test the attention-capturing potential of the listener’s own name in normal speech and time-compressed speech. In Experiment 1, 39 participants were tested with a visual word categorization task with uncompressed spoken names as background auditory distractors. Participants’ word categorization performance was slower when hearing their own name rather than other names, and in a final test, they were faster at detecting their own name than other names. Experiment 2 used the same task paradigm, but the auditory distractors were time-compressed names. Three compression levels were tested with 25 participants in each condition. Participants’ word categorization performance was again slower when hearing their own name than when hearing other names; the slowing was strongest with slight compression and weakest with intense compression. Personally relevant time-compressed speech has the potential to capture attention, but the degree of capture depends on the level of compression. Attention capture by time-compressed speech has practical significance and provides partial evidence for the duplex-mechanism account of auditory distraction.
Unveiling emotion dynamics in problem-solving: a comprehensive analysis with an intelligent tutoring system using facial expressions and electrodermal activities
Authors: Zheng Juan , Li Shan , Wang Tingting , Lajoie Susanne P.
Published: May 2024

Emotions play a crucial role in the learning process, yet there is a scarcity of studies examining emotion dynamics in problem-solving with fine-grained data and advanced tools. This study addresses this gap by investigating the emotional trajectories during self-regulated learning (SRL) phases (i.e., forethought, performance, and self-reflection) among 47 medical students utilizing an intelligent tutoring system. Real-time facial expressions were analyzed through recurrence quantification analysis alongside an examination of electrodermal activities (EDA) across the SRL phases. The findings reveal that emotion stability varied across SRL phases, with students exhibiting more stable emotions during the performance phase. Compared to the forethought and self-reflection phases, students had less frequent and lower intensity of emotional arousal in the performance phase. Moreover, we found that students with better performance demonstrated more stable emotions in the forethought phase, less stable emotions in the self-reflection phase, and a higher level of emotional arousal in the self-reflection phase. These insights highlight the temporal and dynamic nature of emotions in SRL, offering methodological and educational implications for leveraging facial expressions and EDA to monitor and enhance students’ emotional experience during problem-solving.
Family business sustainability: the impact of governance and women’s empowerment in Saudi Arabia
Authors: Al Rawaf Razan Abdullah , Alfalih Abdulaziz Abdulmohsen
Published: May 2024

Due to their strong emotional interest and ownership control, family firm owners significantly influence their firm’s strategies and governance, which has consequences for their business sustainability practices. The failure to establish or maintain formal organizational structures, and adopt good governance principles, may hinder family firms in their pursuit of long-term sustainability. This study empirically investigated the impact of corporate governance on family firms’ sustainability, with women’s empowerment and culture as moderating and mediating factors, respectively. Data for the study were obtained from a sample of 126 family firms from Saudi Arabia. The study adopted the partial least squares structural equation modelling (PLS-SEM) method. The study results empirically confirmed that corporate governance is positively associated with women’s empowerment, which also assists in achieving business sustainability in family-controlled firms. The adoption of good corporate governance policies, and empowerment of women through their appointment on corporate boards operating in a supportive culture, can reinforce an organization’s mission, purpose and strategies, which can create an enabling environment for family business sustainability.
Child sexual abuse, adolescent/adult sexual violence, and sexual functioning among college women: a systematic review
Authors: Bhuptani Prachi H. , Mayer Elizabeth , Chan Georgia , Orchowski Lindsay M.
Published: May 2024

Background

Sexual violence, including childhood sexual abuse and adolescent/adult sexual assault, is a major public health concern, especially for college women. Sexual violence is associated with numerous negative consequences, including difficulties relating to sexual functioning. The current systematic review aimed to synthesize the existing research literature examining the association between sexual violence on sexual functioning among college women.

Methods

Only peer-reviewed articles reporting original data and written in English, which assessed for sexual functioning and sexual violence among a sample of college women, were included in the review. Articles were included if the research study assessed sexual violence occurring in childhood, adolescence, or adulthood.

Results

A total of 21 articles met these inclusion criteria and were included in the synthesis of the literature. In studies of college women, sexual violence occurring in adulthood was associated with worse sexual functioning outcomes among college women in 7 of the 21 studies. Findings were mixed regarding the association between childhood sexual abuse and sexual functioning among college women. Further, in three studies, psychological symptoms (e.g., depression, anxiety) mediated the association between sexual violence in adulthood and worse sexual functioning among college women. Studies varied in what domains of sexual functioning were assessed, and as a result, a limited number of studies included assessments of the same domain of sexual functioning. Further, some studies did not assess sexual violence at multiple points in development (i.e., childhood, adolescence, adulthood).

Conclusions

Future studies with longitudinal designs and a wider range of sexual functioning outcomes are needed, including studies focused on women attending 2-year and technical colleges.
Features of Teaching English to Students of Non-Linguistic Universities with the Manifestation of Semantic and Agrammatic Dyslexia
Authors: Polzikova Evgeniya , Soboleva Elena
Published: May 2024

The article is devoted to the study of the peculiarities of teaching English to students experiencing difficulties in semantic and agrammatic dyslexia. The purpose of the study is to identify effective methods and strategies that can help students overcome these difficulties in the process of learning English in a non-linguistic university. As part of this work, a literature review was conducted, including scientific publications and research on the topic of teaching English in the presence of dyslexia. The classification of dyslexia was considered, its semantic and agrammatic manifestations were highlighted.
As a result of the study, the main difficulties that students face when learning English in the context of dyslexia were highlighted. In the course of the work, recommendations were proposed for English language teachers that will help them to work effectively with students of non-linguistic universities with manifestations of semantic and agrammatic dyslexia.
Formation of Professional Competencies of Future Mathematics Teachers Through a Course in Theory and Methods of Teaching Mathematics
Authors: Kashicyna Yu.
Published: May 2024

The article is devoted to the implementation of the Federal state educational standard of higher education in teaching students of a pedagogical university the methodology of teaching mathematics at school. The tasks of laboratory work of the course of general methods of teaching mathematics, contributing to the formation of professional competencies and the development of labor functions of future teachers of mathematics, are considered. The article is addressed to teachers and students of pedagogical universities, methodologists, mathematics teachers.
Mentoring in Professional Education
Authors: Romanchenko M. , Romanchenko A. , Tinina A.
Published: May 2024

The article analyzes the problem of mentoring in the framework of vocational education, examines the degree of personal relationships between mentor and mentee. It provides an opportunity to understand the importance and relevance of one of the forms of systematic transfer of knowledge and skills by a professional to a young specialist, which is mentoring. Representing the process of introducing a young specialist into professional activity. The author formulates the provisions that make it possible to comprehend the features of mentoring activities carried out by teachers of secondary vocational education in order to form an environment of qualitative formation and intensive development of the process of professional adaptation of a young specialist through mentoring in educational institutions of the Novosibirsk region.
System Approach in the Process of Education of Ligel Literacy of Cadets of Military Universities
Authors: Stec A.
Published: May 2024

The article discusses the methodology of the research, the education of legal literacy of cadets of military universities. The author substantiates the need to use a systematic approach as a general scientific basis for solving the pedagogical problem of educating legal literacy. Based on the results of the study, elements, components, subjects, external and internal aspects and connections in the process of legal literacy education are identified. The effectiveness of the use of a systematic approach that contributes to the consideration of all aspects of legal literacy, from basic legal knowledge to the development of legal behavior and consciousness, has been updated.
Analysis of Anxiety of Students of 1-2 Courses (on the Example of Petrozavodsk State University)
Authors: Tihomirov R. , Guz' Sergey
Published: May 2024

The level of anxiety in modern stressful and foreign policy unfavorable conditions becomes one of the determining factors in the educational process, before the new reforms in the sphere of education there is a problem of organization of pedagogical process in students with high level of anxiety. In this article we study the actual indicators of personality and reactive anxiety in students of Petrozavodsk State University, we obtained data on statistically reliable differences in personality anxiety in students of different genders. We also conducted a systematic analysis of the literature on the platform elibrary.ru, which allowed us to obtain data on the average level of anxiety in students of different institutions of higher education from 2010 to 2022. The used indicators of the results were the values of the methodology ShRLT (Reactive (situational) and personality anxiety scale) C.D. Spielberger-J.L. Khanin.
The Use of the Digital Educational Environment in the Professional Activities of a Teacher
Authors: Khudoverdova S. , Sabel'nikova-Begashvili N. , Damianova E.
Published: May 2024

The article is devoted to one of the important problems of the modern education system – the creation of a modern digital educational environment in educational organizations through the use of digital educational resources, which requires the teacher to have a set of professional competencies. Particular attention is paid to digital educational platforms that can be used to organize educational activities using distance learning technologies and e-learning.
Professional and Public Accreditation As a Tool for Interaction Between Higher Education and Employers
Authors: Kozhuhov S. , Sharonova O. , Sharonov M.
Published: May 2024

The field of education today cannot develop as a closed system, without taking into account the request formulated by employers. The contradiction between the requirements of employers and the results provided by educational organizations is one of the reasons for the decline in the quality of training. It is obvious that the dialogue between the sphere of education and the sphere of work should be based on clear mutual obligations. In many countries, the National Qualifications System (hereinafter referred to as the NSC) is used as a tool that allows building such a dialogue. In our country, according to the 238-FZ “On the independent Assessment of Qualifications”, this is an independent assessment of qualifications, just its introduction into the employment relationship “employer – applicant” and leads to those serious changes in the field of education as a supplier of qualified personnel for the labor market. In this regard, the article attempts to assess the methodological impact of the process of implementing an independent assessment of qualifications on the field of higher education through the created interaction tools, which include professional standards and the procedure of professional and public accreditation, as a system for verifying the fulfillment of their requirements.
After all, it is necessary to be able to correctly assess the degree of achievement of the requirements of professional standards when students master the relevant educational programs of the university, and to focus on achieving this goal the process of designing the educational trajectory of future graduates. Because it is from the competent fulfillment of this condition that in the end the demand for trained personnel in the labor market, and, therefore, the educational program itself, which is already beneficial to the educational organization, will hang.
Berberine in the treatment of type 2 diabetes - literature review
Authors: Mazurek Aleksandra , Pawlicki Mateusz , Stachyrak Karol , Mika Dawid , Mazur Bartosz , Turek Kamila , Lambach Maciej , Greguła Anna , Kłos Aleksandra , Wilanowska Wiktoria
Published: May 2024

Introduction and purpose : 
Type 2 diabetes is currently a serious problem worldwide. Each year, the number of individuals with carbohydrate metabolism disorders is increasing. This is due to an unhealthy lifestyle, lack of physical activity, and a diet rich in highly processed foods. Currently, the treatment of type 2 diabetes is based on the use of oral antidiabetic medications, with the first choice often being a derivative of biguanides, such as metformin. Berberine has been used in China for many years as a hypoglycemic agent, and its efficacy is compared to metformin preparations. This paper focuses on the benefits of using berberine in patients with prediabetes or type 2 diabetes and compares the effects of berberine preparations to classical medications used in diabetes treatment. 
 
Material and methods :  
The literaue was reviewed in PubMed and Google Scholar scientific database in 2013-2023 using the following keywords : berberine, diabetes mellitus type 2, hyperlipidemia, hyperglicemia   
Conclusions : 
The studies included in this manuscript have shown that berberine is a promising agent for adjunctive treatment in type 2 diabetes. It exhibits a range of positive effects such as lowering blood glucose levels, improving lipid profile, with no serious adverse effects reported. However, further research is needed to confirm these findings and develop an effective treatment plan.
Neuroleptic Malignant Syndrome - review of pathophysiology, clinical presentation, differentiation and management
Authors: Strus Karolina , Madera Magdalena , Dąbrowska Natalia , Mazur Sylwia , Zdunek Roksana , Mazur Agata , Nagórska Emilia , Marcinkowski Krzysztof , Bizan Aleksy , Kublińska Aleksandra
Published: May 2024

Introduction and purpose: The number of invented and produced medications has increased over recent years. Besides their positive impact on health, they invariably provide various kinds of side effects. This review is focused on malignant neuroleptic syndrome, a rare condition with no fully confirmed pathogenesis, which at least partially can be explained as an adverse effect of blocking dopamine receptors. Even though it usually affects psychiatric or neurological patients, doctors of all medical specializations should stay alert, as the condition can often lead to premature death.
Brief description of knowledge: The main symptoms associated with NMS are hypertonia, hyperpyrexia, autonomic instability and altered consciousness. They can appear in any configuration, sometimes followed by less characteristic manifestations. It should be primarily differentiated from serotonin syndrome, malignant hyperpyrexia and catatonia, mostly through the interview of those who have taken medications and undergone surgeries, as there are not any specific lab tests available. Fundamental treatment methods consist of neuroleptic withdrawal, intensive supportive care, drug administration and eventually ECT. 
Summary: NMS is an uncommon, severe disease that should be carefully considered in patients treated with neuroleptics. Due to its rarity and sudden onset, it appears to be problematic to conduct widespread research and studies, so there are still no concrete, consistent and unquestioned guidelines on recognizing and treating the condition.
Current approach to diagnosing and treating necrotizing fasciitis
Authors: Ciulkiewicz Łukasz , Kryszpin Paulina , Jachimowski Piotr , Pełka Maciej , Kania Anna , Fijałkowska Justyna
Published: May 2024

Introduction: Necrotizing fasciitis is an infrequent yet highly fatal bacterial infection characterized by widespread necrosis of fascia and subcutaneous fat tissue. Though initial symptoms resemble typical infection, necrotizing fasciitis progresses rapidly triggering acute phase response. Individuals with advanced age, chronically ill, immunocompromised, or abusing alcohol are especially susceptible to developing necrotizing fasciitis. In order to reduce mortality, early diagnosis and appropriate treatment are indispensable.
Aim of the Study: Aim of this study is through evaluating existing literature to outline the contemporary diagnostic strategies and emerging therapy options for necrotizing fasciitis.

Description of the State of Knowledge: Primary diagnostic methods involve clinical evaluation and surgical exploration, complemented by fresh frozen sections for rapid diagnosis and the finger test. Diagnostic imaging incorporates the use of magnetic resonance imaging, computed tomography and ultrasound. The treatment is mostly centered around surgical debridement and antibiotic therapy. Therapies that display potential efficacy include low-dose radiotherapy, hyperbaric oxygen therapy, and the use of intact fish skin grafts for tissue reconstruction after successful treatment. The emerging approach includes therapy targeting systemic inflammatory response syndrome, sepsis induced coagulopathy and critical illness related corticosteroid insufficiency.

 Conclusions: The management of necrotizing fasciitis primarily depends on traditional methods. Fast identification and proper treatment are pivotal in reducing the mortality rate. Recognizing the significance of addressing the acute phase response in necrotizing fasciitis treatment introduces new possibilities for therapeutic interventions. Further research is vital to evaluate the existing approaches to necrotizing fasciitis management and explore new diagnoistic and therapeutic alternatives.
Alternative use of the cough drug - N-acetylcysteine in psychiatry: a review of recent clinical trials
Authors: Cieszkowska Joanna , Czubala Marta , Czerwik Julia , Dmochowska Joanna
Published: May 2024

Introduction and purpose
N-acetylcysteine (NAC) is one of the more popular drugs, widely available in pharmacies, used to treat wet cough. NAC's diverse mechanism of action has drawn the attention of researchers for its great potential in the treatment of many conditions. Indeed, it has been noted that administration of NAC allows indirect modulation of the central nervous system, which may be important in the treatment of psychiatric diseases. The following review focuses on recent reports of NAC's potentially beneficial effects on psychiatric conditions such as depression, schizophrenia, obsessive-compulsive disorder, and addiction.
Description of the state of knowledge
Based on studies conducted on animals (rats), a positive effect of NAC has been proven, observing a reduction in the severity of depressive symptoms. Based on the above data, more and more human studies are being conducted, where the effect of NAC on the symptoms of various mental conditions is being investigated. In recent years, the antioxidant, anti-inflammatory and neurotransmitter function modulating effects of NAC on the brain have been proven, with significant potential in the treatment of mental illness.
Conclusions
The potential impact of NAC on the treatment of mental illness is a rapidly developing topic in recent years. On the basis of available scientific data, partial reduction of symptoms of mental illnesses through the use of NAC has been confirmed. It is a very promising drug, which in this indication requires additional studies to unequivocally confirm its beneficial effects on the functioning of the central nervous system.
Cariprazine: An Antipsychotic Medication with High Therapeutic Potential
Authors: Wilanowska Wiktoria , Greguła Anna , Stachyrak Karol , Mika Dawid , Matuszewska Justyna , Mazur Bartosz , Babkiewicz-Jahn Kamila , Oleksak Izabela , Welian-Polus Iwona , Turek Kamila
Published: May 2024

Introduction and purposeCariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use.Methods and materialsA review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist.ConclusionsCariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations.
New drugs for the treatment of hyperlipidemia in statin-intolerant patients - review
Authors: Płonka Wojciech , Pelc Marcin , Sitarek Gracjan , Żerek Marta , Bułatowicz Monika , Liber Joanna , Banach Krzysztof , Chruścicki Damian , Pławiak Aleksandra
Published: May 2024

Introduction
Cardiovascular diseases are the most numerous group of diseases prevalent in the world. They are a challenge for many health systems, in terms of keeping life comfortable and also economics. The cause of selected disease entities is too much cholesterol in the blood. The most popular treatment for hypercholesterolemia is based on statins. Many patients are affected by intolerance to these drugs, so an important issue is the discovery and improvement of alternatives to statins.
Purpose of work
The purpose of this review is to collect literature data on the latest treatments for hypercholesterolemia with drugs other than statins and ezetimibe.
Materials and methods
Materials are from a review of recent literature available in PubMed. To search for articles, we used keywords such as: bempedoic acid, non-statin therapy, cardiovascular risk, inclisiran, alirocumab, cardiovascular disease, dyslipidemia, evolocumab.
Summary
Treatment of hypercholesterolemia with statins remains the most popular management strategy. Intolerance to treatment with these drugs creates serious clinical problems for patients. Recently, we could see the emergence of new drugs as alternatives to statins. As the results show, the new drugs can effectively replace statins in the hypolipemic treatment especially of patients who cannot be treated with them.
Therapeutic effects of lincomycin and level of drug degradation in broiler tissues after treatment
Authors: Wijayanti Agustina Dwi , Muzaki Alfian Yusak , Wibisono Cahyo , Widiasih Dyah Ayu
Published: May 2024

Background and Aim: Lincomycin is an antibiotic used in broiler farming and is commonly combined with other substances to achieve synergistic and complementary effects on the antibacterial spectrum and mechanism. We developed a specific high-performance liquid chromatography (HPLC) method to measure lincomycin levels in broiler tissues. This study aimed to determine the lincomycin level in tissues and compare it with the minimum inhibitory concentration (MIC) and maximum residue limit (MRL) of certain pathogenic bacteria.

Materials and Methods: Three groups of broiler chickens were involved in the study (n = 20 in each group): A control group without lincomycin treatment and two groups (each further divided into two sub-groups) that received oral lincomycin at a dose of 1 g/10 kg of body weight daily for 7 and 14 consecutive days. Tissue samples were collected from each group 1 day and 1 week after lincomycin administration (ALA). This study validated the development of a technique for analyzing drug level degradation in tissues using HPLC. Descriptive and statistical analyses were performed for drug levels to assess their therapeutic value and safety based on lincomycin MIC of certain pathogenic bacteria and MRL.

Results: The method validation resulted in linear regression and coefficient of determination for tissues with r2 > 0.99, with a recovery rate of 90%–110%, precision as the coefficient of variation 15%, and specificity with no peak overlap for lincomycin. The limits of detection for the liver and kidney were 0.01 μg/g, 0.05 μg/g, and 0.1 μg/g for the breast muscle and all tissues. Administration of lincomycin for 7 and 14 days resulted in therapeutic value concentrations. Lincomycin levels in the liver and kidney of ALA exceeded the MRL, whereas breast muscles were below the MRL for a week of ALA treatment.

Conclusion: Administration of lincomycin for 7 and 14 consecutive days resulted in therapeutic value; however, after a week, most tissues showed high drug concentrations that exceeded the MRL. It is necessary to carefully consider the prolonged therapeutic dose of lincomycin in broilers. Antibiotic therapy must be guided in such a way as to protect the product from harmful residues.

Keywords: : broiler tissues, lincomycin level, maximum residue limit, minimum inhibitory concentration.
Prevalence of the cagA Virulence Factor Varies by Race Among Helicobacter pylori–Infected Patients Undergoing Upper Endoscopy
Authors: Epplein Meira , McCall Shannon J. , Wang Frances , Alagesan Priya , Brown HannahSofia , Wawrzynski Joseph , Labriola Caroline , Zuzul Rachel , Cook Christian , Dillon Melanie , Hyslop Terry , Patierno Steven R. , Salama Nina R. , Garman Katherine S.
Published: May 2024

INTRODUCTION:

We designed a race-conscious study to assess the presence of Helicobacter pylori virulence factor cagA in a retrospective cohort of patients with active H. pylori infection.

METHODS:

We compared cagA status by race in gastric tissue samples from 473 patients diagnosed with active H. pylori infection from 2015 to 2019.

RESULTS:

H. pylori + Black patients were 2 times more likely to be cagA + than H. pylori + White patients (82% vs 36%, P < .0001).

DISCUSSION:

Presence of cagA is common among endoscopy patients with active H. pylori infection; appropriate testing and treatment of H. pylori can both reduce gastric cancer risk and address health disparities.
Ellagic Acid-Changed Epigenome of Ribosomal Genes and Condensed RPA194-Positive Regions of Nucleoli in Tumour Cells
Authors: Legartová S. , Sbardella G. , Kozubek S. , Bártová Eva
Published: May 2024

We studied the effect of ellagic acid (EA) on the morphology of nucleoli and on the pattern of major proteins of the nucleolus. After EA treatment of HeLa cells, we observed condensation of nucleoli as documented by the pattern of argyrophilic nucleolar organizer regions (AgNORs). EA also induced condensation of RPA194-positive nucleolar regions, but no morphological changes were observed in nucleolar compartments positive for UBF1/2 proteins or fibrillarin. Studied morphological changes induced by EA were compared with the morphology of control, non-treated cells and with pronounced condensation of all nucleolar domains caused by actinomycin D (ACT-D) treatment. Similarly as ACT-D, but in a lesser extent, EA induced an increased number of 53BP1-positive DNA lesions. However, the main marker of DNA lesions, γH2AX, was not accumulated in body-like nuclear structures. An increased level of γH2AX was found by immunofluorescence and Western blots only after EA treatment. Intriguingly, the levels of fibrillarin, UBF1/2 and γH2AX were increased at the promoters of ribosomal genes, while 53BP1 and CARM1 levels were decreased by EA treatment at these genomic regions. In the entire genome, EA reduced H3R17 dimethylation. Taken together, ellagic acid is capable of significantly changing the nucleolar morphology and protein levels inside the nucleolus.
Subcellular Localization of Proteins Responding to Mitoxantrone-Induced DNA Damage in Leukaemic Cells
Authors: Ćmielová Jana , Lesná M. , Řezáčová M.
Published: May 2024

The aim of the present study was to investigate the subcellular localization of proteins participating in the double-strand break response pathway – p53, Mdm2, p21 and Chk2. MOLT-4 cells were pre-treated with mitoxantrone in concentrations 1 nmol/l and 5 nmol/l. The trypan blue technique was used to determine cell viability and proliferation. Western blotting was used to evaluate changes in p53, Mdm2 and Chk2 protein expression and sandwich ELISA was used to evaluate changes in the p21 protein amount. After 1 nmol/l mitoxantrone cells did not die, but their ability to proliferate was decreased. The p53 protein was activated and phosphorylated at serines 15 and 392 and accumulated in the nucleus after 24 and 48 h. The Mdm2 protein was present in the cytoplasm with its maximal level after 8 and 16 h. The p21 protein was detected in the nucleus after 24 and 48 h. Increased levels of phosphorylated Chk2 at threonine 68 were observed in the cytoplasmic fraction after 24 and 48 h of mitoxantrone treatment. We used mitoxantrone as an inducer of double-strand breaks to bring new data about the subcellular distribution of proteins responding to DNA damage. In MOLT-4 cells, the p53 protein was activated. p53 was phosphorylated at serines 15 and 392 and accumulated in the nucleus. The Mdm2 protein was activated in advance to p53 and occurred in the cytoplasm. The p21 protein was present in the nucleus. Chk2 kinase was activated by the phosphorylation at threonine 68 and we observed increased levels of this protein in the cytoplasmic fraction.
Noise Stress-Induced Changes in mRNA Levels of Corticotropin-Releasing Hormone Family Molecules and Glucocorticoid Receptors in the Rat Brain
Authors: Eraslan Evren , Akyazi İ. , Ergül-Ekiz E. , Matur E.
Published: May 2024

Noise is a widespread stress resource that may lead to detrimental effects on the health. However, the molecular basis of the stress response caused by noise remains elusive. We have studied the effects of acute and chronic noise stress on stress-related molecules in the hypothalamus and hippocampus and also corticosterone responses. Sprague Dawley rats were randomized into control, acute and chronic noise stress groups. While the chronic noise stress group animals were exposed to 100 dB white noise for 4 h/a day during 30 days, the acute noise stress group of animals was exposed to the same level of stress once for 4 h. The expression profiles of corticotropin- releasing hormone (CRH), CRH1, CRH2 receptors and glucocorticoid receptor (GR) mRNAs were analysed by RT-PCR. Chronic noise stress upregulated CRH mRNA levels in the hypothalamus. Both acute and chronic noise increased CRH-R1 mRNA in the hypothalamus but decreased it in the hippocampus. GR mRNA levels were decreased by chronic noise stress in the hippocampus. The present results suggest that while corticosterone responses have habituated to continuous noise stress, the involvement of CRH family molecules and glucocorticoid receptors in the noise stress responses are different and structure specific.
Curcumin-Mediated Reversal of p15 Gene Promoter Methylation: Implication in Anti-Neoplastic Action against Acute Lymphoid Leukaemia Cell Line
Authors: Sharma V. , Jha A. K. , Kumar A. , Bhatnagar A. , Narayan G. , Kaur Jagdeep
Published: May 2024

Curcumin has been documented to exert anticancer effects by interacting with altered proliferative and apoptotic pathways in cancer models. In this study, we evaluated the potential of curcumin to reverse promoter methylation of thep15gene in Raji cells and its ability to induce apoptosis and genomic instability. Anti-neoplastic action of curcumin showed an augmentation in reactive oxygen species (ROS) and cell cycle arrest in G1 phase. Subsequently, curcumin- exposed Raji cells showed structural abnormalities in chromosomes. These observations suggest that curcumin also causes ROS-mediated apoptosis and genomic instability. The treatment of Raji cell line with 10 μM curcumin caused hypomethylation of thep15promoter after six days. Hypomethylation ofp15was further found to be favoured by downregulation of DNA methyltransferase 1 after 10 μM curcumin treatment for six days. Methylation-specific PCR suggested demethylation of thep15promoter. Demethylation was further validated by DNA sequencing. Reverse-transcription PCR demonstrated that treatment with curcumin (10 μM) for six days led to the up-regulation ofp15and down-regulation of DNA methyltransferase 1. Furthermore, curcumin- mediated reversal ofp15promoter methylation might be potentiated by down-regulation of DNA methyltransferase 1 expression, which was supported by cell cycle analysis. Furthermore, curcumin acts as a double-pronged agent, as it caused apoptosis and promoter hypomethylation in Raji cells.
Bioactivities of Prunus mahaleb: A Mini Review
Authors: Ibrahim Nabaa Mohammed , Abdul-jalil Thukaa Zuhair , Mahmood Ahmed Salim
Published: May 2024

The mahaleb cherry, which has the scientific name Prunus mahaleb L., is a fragrant shrub plant belonging to the Rosaceae family. The plant is commonly cultivated in the Mediterranean area. The people cultivated it for its essential oil and seeds, which have great therapeutic and nutritional value. It is widely distributed over North Africa, Central Asia, and Central-South Europe. The plant contains a variety of active constituents like coumarins, vital oils, polyphonic ingredients, and other phytochemical compounds that possess many pharmacological activities capable of improving people’s health. These activities include antioxidant, antimicrobial, anti-inflammatory, gastro-protective, neuroprotective, and diabetic management actions. Overall data for this literature review was collected from online sources such as Google Scholar, Science Direct, Scopus, Research Gate, Elsevier, PubMed, and Web Science. In addition to that, the library of the pharmacognosy department was utilized to collect supplementary information on photochemical constituents, pharmacognosy, and pharmacological applications of mahaleb cherry. The gathered data was carefully examined and authenticated. The main aim of this review article is to uncover potential therapeutic activities of this plant that could be valuable in the future for therapeutic nutrition, as well as food and pharmaceutical industries.