bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of drug-induced metabolic enzyme activity inhibition and CYP3A4 gene polymorphism on aumolertinib metabolism
Authors: Ye Feng , Ni Jinhuan , Li Xinyue , Wang Jing , Luo Jianchao , Wang Shiyu , Xu Xiaoyu , Zhong Yunshan , Qian Jianchang , Xiao Zhongxiang 
Published: May 2024

The purpose of this study is to clarify the drug interaction profile of aumolertinib, and the influence of CYP3A4 genetic polymorphism on aumolertinib metabolic characteristics. Through microsomal enzyme reactions, we screened 153 drugs and identified 15 that significantly inhibited the metabolism of aumolertinib. Among them, telmisartan and carvedilol exhibited potent inhibitory activities in rat liver microsomes (RLM) and human liver microsomes (HLM). In vivo, the pharmacokinetic parameters of aumolertinib, including AUC and Cmax, were significantly altered when co-administered with carvedilol, with a notable decrease in the clearance rate CLz/F. Interestingly, the pharmacokinetic parameters of the metabolite HAS-719 exhibited a similar trend as aumolertinib when co-administered. Mechanistically, both telmisartan and carvedilol exhibited a mixed-type inhibition on the metabolism of aumolertinib. Additionally, we used a baculovirus-insect cell expression system to prepare 24 recombinant CYP3A4 microsomes and obtained enzymatic kinetic parameters using aumolertinib as a substrate. Enzyme kinetic studies obtained the kinetic parameters of various CYP3A4 variant-mediated metabolism of aumolertinib. Based on the relative clearance rates, CYP3A4.4, 5, 7, 8, 9, 12, 13, 14, 17, 18, 19, 23, 24, 33, and 34 showed significantly lower clearance rates compared to the wild-type. Among the different CYP3A4 variants, the inhibitory potency of telmisartan and carvedilol on the metabolism of aumolertinib also varied. The IC50 values of telmisartan and carvedilol in CYP3A4.1 were 6.68 ± 1.76 μM and 0.60 ± 0.25 μM, respectively, whereas in CYP3A4.12, the IC50 exceeded 100 μM. Finally, we utilized adeno-associated virus to achieve liver-specific high expression of CYP3A4*1 and CYP3A4*12. In the group with high expression of the less active CYP3A4*12, the magnitude of the drug-drug interaction was significantly attenuated. In conclusion, CYP3A4 genetic polymorphism not only influences the pharmacokinetic characteristics of aumolertinib, but also the inhibitory potency of telmisartan and carvedilol on it.
Empathy in schizophrenia: neural alterations during emotion recognition and affective sharing
Authors: Knobloch Simon , Leiding Delia , Wagels Lisa , Regenbogen Christina , Kellermann Thilo , Mathiak Klaus , Schneider Frank , Derntl Birgit , Habel Ute 
Published: May 2024

IntroductionDeficits in emotion recognition and processing are characteristic for patients with schizophrenia [SCZ].MethodsWe targeted both emotion recognition and affective sharing, one in static and one in dynamic facial stimuli, during functional magnetic resonance imaging [fMRI] in 22 SCZ patients and 22 matched healthy controls [HC]. Current symptomatology and cognitive deficits were assessed as potential influencing factors.ResultsBehaviorally, patients only showed a prolonged response time in age-discrimination trials. For emotion-processing trials, patients showed a difference in neural response, without an observable behavioral correlate. During emotion and age recognition in static stimuli, a reduced activation of the bilateral anterior cingulate cortex [ACC] and the right anterior insula [AI] emerged. In the affective sharing task, patients showed a reduced activation in the left and right caudate nucleus, right AI and inferior frontal gyrus [IFG], right cerebellum, and left thalamus, key areas of empathy.DiscussionWe conclude that patients have deficits in complex visual information processing regardless of emotional content on a behavioral level and that these deficits coincide with aberrant neural activation patterns in emotion processing networks. The right AI as an integrator of these networks plays a key role in these aberrant neural activation patterns and, thus, is a promising candidate area for neurofeedback approaches.
Knowledge, attitude, and practice toward ultrasound screening for breast cancer among women
Authors: Liu Shaozhong , Zheng Shukai , Qin Mengzhen , Xie Yifeng , Yang Kun , Liu Xiaozhen 
Published: May 2024

BackgroundSeveral obstacles can hinder breast cancer screening. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward ultrasound screening for breast cancer in women.MethodsThis cross-sectional study recruited women who visited the breast specialist clinic of Zhongshan City People’s Hospital (a tertiary hospital) between August 2022 and April 2023 through convenience sampling. KAP scores ≥70% were considered adequate.ResultsThis study enrolled 501 participants. The mean knowledge, attitude, and practice levels were 8.56 ± 1.81/12 (possible range 0–12, 71.33%), 29.80 ± 2.71 (possible range 8–40, 74.50%), and 32.04 ± 3.09 (possible range 8–40, 80.10%). Senior high school education (vs. junior high school and below, coefficient = 1.531, 95%CI: 1.013–2.312, p = 0.044), bachelor’s education and above (vs. junior high school and below, coefficient = 5.315, 95%CI: 3.546–7.966, p &lt; 0.001), housewife or unemployed (vs. employed, coefficient = 0.671, 95%CI: 0.466–0.966, p = 0.032), and a history of breast ultrasound (vs. no, coefficient = 1.466, 95%CI: 1.121–1.917, p = 0.005) were independently and positively associated with knowledge. Knowledge (coefficient = 1.303, 95%CI: 1.100–1.544, p = 0.002) and monthly income &gt;10,000 (vs. &lt;5,000, coefficient = 4.364, 95%CI: 1.738–10.956, p = 0.002) were independently and positively associated with attitude. Only attitude (coefficient = 1.212, 95%CI: 1.096–1.340, p &lt; 0.001) was independently and positively associated with the practice. A structural equation modeling (SEM) analysis was used to estimate causality among KAP dimensions, showing that knowledge directly influenced attitude (β = −1.090, p = 0.015), knowledge did not directly influence practice (β = −0.117, p = 0.681) but had an indirect influence (β = 0.826, p = 0.028), and attitude directly influenced practice (β = −0.757, p = 0.016).ConclusionWomen in Zhongshan City had good knowledge, favorable attitudes, and active practice toward breast ultrasound screening for breast cancer. Women’s characteristics associated with a poorer KAP were identified, allowing for more targeted interventions.
Comprehensive transcriptomic and metabolomic analysis of porcine intestinal epithelial cells after PDCoV infection
Authors: Wang Guangzheng , Cao Yanan , Xu Chao , Zhang Shuoshuo , Huang Yanjie , Zhang Shuai , Bao Wenbin 
Published: May 2024

IntroductionPorcine deltacoronavirus (PDCoV), an emerging swine enteropathogenic coronavirus with worldwide distribution, mainly infects newborn piglets with severe diarrhea, vomiting, dehydration, and even death, causing huge economic losses to the pig industry. However, the underlying pathogenic mechanisms of PDCoV infection and the effects of PDCoV infection on host transcripts and metabolites remain incompletely understood.MethodsThis study investigated a combined transcriptomic and metabolomic analysis of porcine intestinal epithelial cells (IPEC-J2) following PDCoV infection by LC/MS and RNA-seq techniques. A total of 1,401 differentially expressed genes and 254 differentially accumulated metabolites were detected in the comparison group of PDCoV-infected vs. mock-infected.Results and discussionWe found that PDCoV infection regulates gene sets associated with multiple signaling pathways, including the neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, MAPK signaling pathway, chemokine signaling pathway, ras signaling pathway and so on. Besides, the metabolomic results showed that biosynthesis of cofactors, nucleotide metabolism, protein digestion and absorption, and biosynthesis of amino acid were involved in PDCoV infection. Moreover, integrated transcriptomics and metabolomics analyses revealed the involvement of ferroptosis in PDCoV infection, and exogenous addition of the ferroptosis activator erastin significantly inhibited PDCoV replication. Overall, these unique transcriptional and metabolic reprogramming features may provide a better understanding of PDCoV-infected IPEC-J2 cells and potential targets for antiviral treatment.
Oral Administration of Lactobacillus acidophilus LA5 Prevents Alveolar Bone Loss and Alters Oral and Gut Microbiomes in a Murine Periodontitis Experimental Model
Authors: Cataruci Amalia C. S. , Kawamoto Dione , Shimabukuro Natali , Ishikawa Karin H. , Ando-Suguimoto Ellen S. , Ribeiro Rodolfo A. , Nicastro Gianlucca G. , Albuquerque-Souza Emanuel , de Souza Robson F. , Mayer Marcia P. A. 
Published: May 2024

Periodontitis is a destructive inflammatory response triggered by dysbiosis. Lactobacillus acidophilus LA5 (LA5) may impair microbial colonization and alter the host. Thus, we evaluated the effect of LA5 on alveolar bone loss in a periodontitis murine model and investigated its effect on the oral and gut microbiomes. Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Streptococcus gordonii were inoculated in C57BL/6 mice (P+), with LA5 (L+). SHAM infected controls (P- and/or L- groups) were also evaluated. After 45 days, alveolar bone loss in the maxilla and oral and gut microbiomes were determined. The administration of LA5 controlled the microbial consortium-induced alveolar bone loss. Periodontopathogens infection resulted in shifts in the oral and gut microbiomes consistent with dysbiosis, and LA5 reshaped these changes. The oral microbiome of P+L- group showed the increased abundance of Enterococaccea, Streptoccocaceae, Staphylococcaceae, Moraxellaceae, and Pseudomonadaceae, which were attenuated by the administration of LA5 to the infected group (P+L+). The administration of LA5 to otherwise non-infected mice resulted in the increased abundance of the superphylum Patescibacteria and the family Saccharamonadaceae in the gut. These data indicate L. acidophilus LA5 as a candidate probiotic for the control of periodontitis.
Cough in Clinical Practice: Approaches to Assessment and Treatment
Authors: Антонович Ж.В. 
Published: May 2024

В повседневной клинической практике кашель является наиболее распространенным симптомом. Понимание причин и механизмов кашля помогает назначить оптимальную терапию. Оценка продолжительности кашля позволяет определить его возможные причины и потенциальные диагнозы, а также выбрать алгоритм ведения пациента. Монтелукаст (Синглон®) представляет собой препарат выбора при хроническом кашле и гиперреактивности дыхательных путей, включая постковидный период. Инозин пранобекс (Гроприносин®) может рассматриваться как эффективный и безопасный лекарственный препарат для лечения и профилактики вирусных инфекций, гриппа и COVID-19-инфекции, способных приводить к стойкой иммуносупрессии, гиперреактивности дыхательных путей и затяжному кашлю.
In everyday clinical practice, cough is the most common symptom. Understanding the causes and mechanisms of cough helps prescribe optimal therapy. Evaluation of the cough duration allows one to determine its possible causes and potential diagnoses, as well as to choose a patient management algorithm. Montelukast (Singlon®) is the drug of choice for chronic cough and airway hyperresponsiveness, including the post-COVID period. Inosine pranobex (Groprinosin®) can be considered as an effective and safe drug for the treatment and prevention of viral infections, influenza and COVID-19, which can lead to persistent immunosuppression, airway hyperresponsiveness and prolonged cough.
Clinical and Pharmacological Characterization of Sulfonylurea Preparations: Conclusions for Outpatient Practice
Authors: Голубев С.А. 
Published: May 2024

Арсенал средств для лечения сахарного диабета второго типа в настоящее время существенно расширился. Препараты – производные сульфонилмочевины являются одним из старейших классов сахароснижающих средств и широко применяются до настоящего времени. В данном практико-ориентированном обзоре представлены имеющиеся данные и научные доказательства по вопросам сравнительной эффективности и безопасности препаратов сульфонилмочевины. Кратко отражены вопросы разработки, классификации и механизма действия представителей данной группы. Представлены параметры фармакокинетики, требующие учета при рациональном клиническом применении, и характеристики сахароснижающего действия. Описаны основные вопросы оценки и коррекции профиля безопасности, включая гипогликемию, увеличение массы тела, сердечно-сосудистую безопасность. Отражены основания для индивидуального дифференцированного применения различных препаратов данного класса, включая учет нарушения функции почек и печени, длительности действия. Даны рекомендации по дифференцированному выбору препаратов сульфонилмочевины, врачебной тактике по оптимизации эффективности и безопасности применения. Подчеркнута оптимальность применения гликвидона при диабетической нефропатии. Определено место препаратов сульфонилмочевины в современной иерархии антигипергликемических средств. Препараты сульфонилмочевины продолжают занимать достойное место в качестве препаратов второй линии лечения сахарного диабета второго типа в составе комбинированной терапии с метформином.
The arsenal of agents for the treatment of type 2 diabetes mellitus has now significantly expanded. Sulfonylurea derivative drugs are one of the oldest classes of sugar-lowering agents and are widely used to date. This practice-oriented review presents the available data and scientific evidence on the comparative efficacy and safety of sulfonylureas. The development, classification and mechanism of action of this group are summarized. Pharmacokinetic parameters to be taken into account in rational clinical use and characteristics of sugar-lowering effect are presented. The main issues of safety profile assessment and correction are described, including hypoglycemia, weight gain, cardiovascular safety. The grounds for individual differentiated use of various drugs of this class, including consideration of renal and hepatic dysfunction, duration of action are reflected. Recommendations on differentiated choice of sulfonylurea drugs, medical tactics to optimize the effectiveness and safety of use are given. Optimality of glyquidone use in diabetic nephropathy is emphasized. The place of sulfonylurea drugs in the modern hierarchy of antihyperglycemic agents has been determined. SM drugs continue to occupy a worthy place as second-line drugs for the treatment of type 2 diabetes mellitus in combination therapy with metformin.
Peripheral Blood Biomarker Krebs von den Lungen 6 (KL-6) for Interstitial and Other Lung Diseases
Authors: Суркова Л.К. , Будник О.А. , Иванова А.Л. , Давидовская Е.И. , Богуш Л.С. 
Published: May 2024

В статье обсуждается диагностическая и прогностическая значимость сывороточного биомаркера Krebs von den Lungen 6 (KL-6) при различных интерстициальных и других заболеваниях легких. Показана возможность использования биомаркера KL-6 для прогнозирования течения и исхода заболевания, тяжести и оценки активности отдельных интерстициальных болезней легких. Отмечено, что повышение уровня KL-6 ассоциируется с тяжестью легочного фиброза. Биомаркер KL-6 может быть использован для прогнозирования развития легочного фиброза и других осложнений COVID-19. Материал содержит рекомендации экспертной группы ATS/ERS/JRS/АЛАТ по использованию сывороточных биомаркеров для дифференциальной диагностики идиопатического легочного фиброза от других интерстициальных заболеваний легких. Подчеркивается необходимость дальнейшего проведения исследований для получения доказательной базы клинической эффективности биомаркера KL-6 (в т. ч. в совокупности с другими биомаркерами).
The diagnostic and prognostic significance of the serum biomarker Krebs von den Lungen-6 (KL-6) in various interstitial and other lung diseases is discussed. The possibility of using the KL-6 biomarker for predicting the course and outcome of the disease, severity and evaluation of the activity of individual interstitial lung diseases is shown. It was noted that an increase in the level of KL-6 is associated with the severity of pulmonary fibrosis. The KL-6 biomarker can be used to predict the development of pulmonary fibrosis and other complications of COVID-19. The material contains the recommendations of the ATS/ERS/JERS/ALAT expert group on the use of serum biomarkers for differential diagnosis of idiopathic pulmonary fibrosis from other interstitial pulmonary diseases are given. The necessity of further research is emphasized in order to obtain an evidence base for the clinical efficacy of the KL-6 biomarker (including in combination with other biomarkers).
O ICMS/ST * E SUA INFLUÊNCIA NA FORMAÇÃO DO PREÇO: UM ESTUDO DE CASO EM UM COMÉRCIO VAREJISTA DE BOCA DO ACRE
Authors: Freitas Antonia Lima de , Freitas Nelciane Lima de , Santana Elizângela Leão 
Published: May 2024

O presente artigo trata sobre os efeitos do ICMS/ST na formação dos preços dos produtos no comércio varejista de Boca do Acre. Um estudo de caso em que o objeto analisado foi um comércio de varejo, inscrito sob a forma de microempresa individual, adepto do simples nacional e tem como finalidade comercial a venda de produtos de vários segmentos com dominância para os do gênero alimentício. Nesse sentido, visou-se destacar os desafios e dificuldades enfrentados pelo comércio na precificação dos produtos, enfatizando as implicações do ICMS/ST, os conceitos e legislações do ICMS/ST. Por meio do objetivo principal, buscou-se entender os efeitos do ICMS/ST na composição de preço das mercadorias que estão sujeitos à tributação e como o comércio analisado tem feito a precificação dos produtos. A pesquisa utilizou a abordagem qualitativa, realizada através de um longo estudo bibliográfico. As conclusões do estudo apontam a relevância do ICMS/ST sobre o preço final do produto, além de revelar que o tributo acima citado não é considerado para precificar os produtos, bem como, o administrador não usa métodos que considere todos os custos atrelado a mercadoria, fazendo-o de forma informal baseados na cultura local.
Vietnamese Speech Act Realization and Some Factors Influencing Refusal Strategies: A Pilot Study
Authors: Bui Tuyen 
Published: May 2024

The purpose of this pilot research was to explore the refusal strategies and factors influencing speech act realization of refusals employed by a group of Vietnamese language learners when making refusals to invitations, requests, offers, and suggestions by 5 participants at Tien Giang University to shed light on the possible problems leading to cross-cultural differences in communication. A Written Discourse Completion Test (WDCT) and 5 interview questions in English versions developed by the researcher were used to collect the data and analyze it qualitatively and quantitatively. The results illustrated that the participants frequently used indirect strategies for refusing each context given in the WDCT. Furthermore, based on the participants’ answers via the interview records, it could be concluded that social contexts, distance, and cross-cultural differences influenced L2 learners of English as a Foreign Language. The findings of this study highlight some strategies to help learners understand and gain more strategies in speech act realization of refusals and misunderstanding can be avoided. Besides, the interlocutors can receive appropriate responses to refusing invitations, requests, offers, and suggestions.
Pelatihan Manajemen Masjid bagi Pengurus Masjid Nurul Huda di Desa Hulim Kecamatan Sosopan, Tapanuli Selatan
Authors: Handayani Ricka , Lubis Armansyah , Hasibuan Hasbi Anshori , Yonda Ade , Azizah Wafiq , Harianto  , Siregar Aulina Safitri , Hasibuan Siti Aminah , Arnada Feby 
Published: May 2024

Pelatihan ini bertujuan meningkatkan pengetahuan dan keterampilan dalam manajemen organisasi bagi Pengurus Masjid Nurul Huda desa Hulim Kecamatan Sosopan. Hal ini bertujuan agar para pengurus dapat bekerja sama secara efisien dan terencana sesuai dengan tugas pokok dan fungsi untuk mencapai tujuan organisasi. Kegiatan ini dimaksudkan untuk memberikan pemahaman tentang manajemen masjid yang dapat mengakomodasi perubahan dalam masyarakat yang berkembang. Kami juga ingin membantu Pengurus Masjid Nurul Huda dalam Menyusun struktur organisasinya dengan baik, dengan usaha sekecil mungkin namun menghasilkan hasil maksimal. Pelatihan dimulai dengan penjelasan tentang konsep dasar manajemen, termasuk empat fungsi manajemen yaitu Perencanaan, Pengorganisasian, Pelaksanaan, dan Pengendalian. Pelatihan ini di akhiri dengan membantu pengurus masjid untuk Menyusun struktur organisasi masjid. Kami berharap melalui pelatihan ini, proses manajemen di masjid Nurul Huda dapat berjalan lancar, dan pengurus serta anggota organisasi dapat memahami tugas mereka serta prinsip-prinsip manajemen organisasi. Kegiatan pelatihan ini akan menekankan pada pengalaman langsung dan praktik dalam mengelola organisasi sehingga pengurus dan anggota masjid dapat mempraktekkan konsep manajemen yang telah dipelajari.
Bodies with Organs, Bodies without Organs
Authors: Thumiger Chiara 
Published: May 2024

Chapter 3 by Chiara Thumiger explores two key perspectives on the human body: localization (parts, organs, ‘systems’) and that of holism, with the first more often than the second expected to be coupled with mechanicistic views. This paper wants to probe this simplification by exploring how, in certain contexts, holistic images of the body have been seen as challenges to the oppressive, dehumanising potential of a fractured view of human physiology as reliant on mechanic, organ-based processes. As such, this ‘holistic body’ is cast as more private, less exposed to subjugation, even subversive by comparison with a body composed of purposeful ‘organs’ and ‘systems’ whose functions and workings are explicable and accessible through anatomical investigation; exposed to specific dynamics and rhythms (flows, beats, pulsations, contractions), and condemned to a predictable existence.
nuance: Efficient Detection of Planets Transiting Active Stars
Authors: Garcia Lionel J. , Foreman-Mackey Daniel , Murray Catriona A. , Aigrain Suzanne , Feliz Dax L. , Pozuelos Francisco J. 
Published: May 2024

Abstract
The detection of planetary transits in the light curves of active stars, featuring correlated noise in the form of stellar variability, remains a challenge. Depending on the noise characteristics, we show that the traditional technique that consists of detrending a light curve before searching for transits alters their signal-to-noise ratio and hinders our capability to discover exoplanets transiting rapidly rotating active stars. We present nuance, an algorithm to search for transits in light curves while simultaneously accounting for the presence of correlated noise, such as stellar variability and instrumental signals. We assess the performance of nuance on simulated light curves as well as on the Transiting Exoplanet Survey Satellite light curves of 438 rapidly rotating M dwarfs. For each data set, we compare our method to five commonly used detrending techniques followed by a search with the Box-Least-Squares algorithm. Overall, we demonstrate that nuance is the most performant method in 93% of cases, leading to both the highest number of true positives and the lowest number of false-positive detections. Although simultaneously searching for transits while modeling correlated noise is expected to be computationally expensive, we make our algorithm tractable and available as the JAX-powered Python package nuance, allowing its use on distributed environments and GPU devices. Finally, we explore the prospects offered by the nuance formalism and its use to advance our knowledge of planetary systems around active stars, both using space-based surveys and sparse ground-based observations.