bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety assessment of deutetrabenazine: real-world adverse event analysis from the FAERS database
Authors: Shu Yanping , Wang Yuanhe , Liu Jiaoying , Hu Lingyan , Tong Sichao , Wu Gang , Zhu Xianlin 
Published: December 2024

BackgroundDeutetrabenazine is a widely used drug for the treatment of tardive dyskinesia (TD), and post-marketing testing is important. There is a lack of real-world, large-sample safety studies of deutetrabenazine. In this study, a pharmacovigilance analysis of deutetrabenazine was performed based on the FDA Adverse Event Reporting System (FAERS) database to evaluate its relevant safety signals for clinical reference.MethodsAdverse events (AEs) of FAERS with deutetrabenazine as the primary suspect drug were collected from the first quarter (Q1) of 2017 to Q1 of 2024. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) were used to mine AEs risk signals of deutetrabenazine. AEs were standardized and classified using the System Organ Class (SOC) and Preferred Terms (PTs) from Medical Dictionary for Regulatory Activities (MedDRA) version 23.0.ResultsA total of 3,583 AEs with deutetrabenazine as the primary suspect drug were collected in this study. We found that these AEs involved 23 SOCs, and the positive signals were mainly concentrated in systemic disease and various reactions at the site of administration (n = 1816, ROR = 1.23, PRR = 1.18, IC = 0.24, EBGM = 1.18), neurological disorders (n = 1736, ROR = 3.02, PRR = 2.60, IC = 1.38, EBGM = 2.60) and psychiatric disorders (n = 1,659, ROR = 4.15, PRR = 3.52, IC = 1.82, EBGM = 3.52). We eventually identified 100 valid PTs that met the criteria of the four algorithms. Drug ineffective, dyskinesia, depression, somnolence, suicidal ideation were considered to be the common PTs of deutetrabenazine. Tongue thrust (n = 4, ROR 253.47, PRR 253.35, IC 7.88, EBGM 235.95), grunting (n = 5, ROR 78.49, PRR 78.45, IC 6.26, EBGM 76.71) and drooling (n = 17, ROR 13.21, PRR 13.19, IC 3.72, EBGM 13.14) were not mentioned in the specification, but the high signal intensity suggested that they may be the potential adverse reactions.ConclusionThe efficacy of deutetrabenazine may be accompanied by some potential adverse effects in several systems. Adverse events in psychiatric, neurologic, gastrointestinal and respiratory need to be monitored in clinical practice.
Suppression of MT5-MMP Reveals Early Modulation of Alzheimer’s Pathogenic Events in Primary Neuronal Cultures of 5xFAD Mice
Authors: Pilat Dominika , Paumier Jean-Michel , Louis Laurence , Manrique Christine , García-González Laura , Stephan Delphine , Bernard Anne , Pardossi-Piquard Raphaëlle , Checler Frédéric , Khrestchatisky Michel , Di Pasquale Eric , Baranger Kévin , Rivera Santiago 
Published: December 2024

We previously reported that membrane-type 5-matrix metalloproteinase (MT5-MMP) deficiency not only reduces pathological hallmarks of Alzheimer’s disease (AD) in 5xFAD (Tg) mice in vivo but also impairs interleukin-1 beta (IL-1β)-mediated neuroinflammation and Aβ production in primary Tg immature neural cell cultures after 11 days in vitro. We now investigate the effect of MT5-MMP on incipient pathogenic pathways that are activated in cortical primary cultures at 21–24 days in vitro (DIV), during which time neurons are organized into a functional mature network. Using wild-type (WT), MT5-MMP−/− (MT5−/−), 5xFAD (Tg), and 5xFADxMT5-MMP−/− (TgMT5−/−) mice, we generated primary neuronal cultures that were exposed to IL-1β and/or different proteolytic system inhibitors. We assessed neuroinflammation, APP metabolism, synaptic integrity, and electrophysiological properties using biochemical, imaging and whole-cell patch-clamp approaches. The absence of MT5-MMP impaired the IL-1β-mediated induction of inflammatory genes in TgMT5−/− cells compared to Tg cells. Furthermore, the reduced density of dendritic spines in Tg neurons was also prevented in TgMT5−/− neurons. IL-1β caused a strong decrease in the dendritic spine density of WT neurons, which was prevented in MT5−/− neurons. However, the latter exhibited fewer spines than the WT under untreated conditions. The spontaneous rhythmic firing frequency of the network was increased in MT5−/− neurons, but not in TgMT5−/− neurons, and IL-1β increased this parameter only in Tg neurons. In terms of induced somatic excitability, Tg and TgMT5−/− neurons exhibited lower excitability than WT and MT5−/−, while IL-1β impaired excitability only in non-AD backgrounds. The synaptic strength of miniature global synaptic currents was equivalent in all genotypes but increased dramatically in WT and MT5−/− neurons after IL-1β. MT5-MMP deficiency decreased endogenous and overexpressed C83 and C99 levels but did not affect Aβ levels. C99 appears to be cleared by several pathways, including γ-secretase, the autophagolysosomal system, and also α-secretase, via its conversion to C83. In summary, this study confirms that MT5-MMP is a pivotal factor affecting not only neuroinflammation and APP metabolism but also synaptogenesis and synaptic activity at early stages of the pathology, and reinforces the relevance of targeting MT5-MMP to fight AD.
Novel 4-alkoxy Meriolin Congeners Potently Induce Apoptosis in Leukemia and Lymphoma Cells
Authors: Krings Karina S. , Wassenberg Tobias R. , Cea-Medina Pablo , Schmitt Laura , Lechtenberg Ilka , Llewellyn Tanya R. , Qin Nan , Gohlke Holger , Wesselborg Sebastian , Müller Thomas J. J. 
Published: December 2024

Meriolins (3-(pyrimidin-4-yl)-7-azaindoles) are synthetic hybrids of the naturally occurring alkaloids variolin and meridianin and display a strong cytotoxic potential. We have recently shown that the novel derivative meriolin 16 is highly cytotoxic in several lymphoma and leukemia cell lines as well as in primary patient-derived lymphoma and leukemia cells and predominantly targets cyclin-dependent kinases (CDKs). Here, we efficiently synthesized nine novel 2-aminopyridyl meriolin congeners (3a–3i), i.e., pyrimeriolins, using a one-pot Masuda borylation-Suzuki coupling (MBSC) sequence, with eight of them bearing lipophilic alkoxy substituents of varying length, to systematically determine the influence of the alkoxy sidechain length on the biological activity. All the synthesized derivatives displayed a pronounced cytotoxic potential, with six compounds showing IC50 values in the nanomolar range. Derivatives 3b–3f strongly induced apoptosis and activated caspases with rapid kinetics within 3–4 h in Jurkat leukemia and Ramos lymphoma cells. The induction of apoptosis by the most potent derivative 3e was mediated by the intrinsic mitochondrial death pathway, as it was blocked in caspase-9 deficient and Apaf-1 knockdown Jurkat cells. However, as recently shown for meriolin 16, derivative 3e was able to induce apoptosis in the Jurkat cells overexpressing the antiapoptotic protein Bcl-2. Since tumor cells often inactivate the intrinsic mitochondrial apoptosis pathway (e.g., by overexpression of Bcl-2), these meriolin congeners represent promising therapeutic agents for overcoming therapeutic resistance.
Heat-Killed Lactobacillus delbrueckii subsp. lactis 557 Extracts Protect Chondrocytes from Osteoarthritis Damage by Reducing Inflammation: An In Vitro Study
Authors: Hu Yu-Chen , Huang Tzu-Ching , Hsieh Bau-Shan , Huang Li-Wen , Lin Jin-Seng , Hsu Han-Yin , Lee Chia-Chia , Chang Kee-Lung 
Published: December 2024

Background: Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed Lactobacillus delbrueckii subsp. lactis 557 (LDL557) could significantly decrease OA progression. Methods: Accordingly, we designed an in vitro cell culture study aimed at investigating the effects of heat-killed LDL557 extracts on chondrocytes using SW1353 cells (a human chondrosarcoma cell line) challenged with 5 μM MIA to mimic OA conditions. Results: The results showed that the 10 μg/mL LDL557 extracts protected SW1353 cells from MIA-induced death and reduced extracellular matrix (ECM) loss, as evaluated by toluidine blue O staining and extracellular matrix component synthesis with RT-qPCR measurement. This was achieved by decreasing the expression of MIA-induced pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, while slightly increasing the MIA-suppressed expression of the anti-inflammatory cytokine IL-10, which were evidenced by RT-qPCR analysis. Moreover, the RT-qPCR evaluation also indicated that the LDL557 extracts slightly reduced the expression of COX-2 compared with the control, while it did not reduce the MIA-increased expression of microsomal prostaglandin E synthase-1 (mPGES-1). In addition, the LDL557 extracts influenced neither the matrix-degrading protease expressions measured via RT-qPCR nor the oxidative stress measured via fluorescence flow cytometry in the cells with or without the MIA challenge. Conclusions: This study demonstrates that LDL557 extracts may protect chondrocytes from OA damage by reducing inflammation-related factors and thus mitigating cartilage matrix loss, suggesting LDL557 extracts are attractive alternatives for OA applications.
Depressive Symptoms in Adults with Autosomal Dominant Polycystic Kidney Disease
Authors: Yi. Caroline J. , Watnick Terry , Seliger Stephen L. 
Published: December 2024

Background:
Individuals with autosomal dominant polycystic kidney disease (ADPKD) face mental health challenges linked to disease progression and its heritable nature. Prior studies reported mixed associations between depressive symptoms and ADPKD severity and progression. Here, we assessed depressive symptoms and disease severity over three years in ADPKD patients without end-stage kidney disease.

Methods:
283 adults with ADPKD were enrolled from April 2013 to June 2023 in a single-center prospective observational study. ADPKD severity was assessed with estimated GFR and htTKV. Depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II). Depressive symptom burden was compared to previously reported cohorts of patients with other chronic, progressive diseases. The relationship of ADPKD severity and ADPKD-related pain with depressive symptoms was estimated using multiple linear regression, adjusting for potential confounders.

Results:
Among 283 adult ADPKD patients(mean age 45; 81% White; 61% female), 15.5% reported moderate depressive symptoms (BDI-II ≥ 11). Depressive symptom prevalence (all ages) was lower than in primary care samples. For the older individuals in our cohort, depressive symptom prevalence was similar to those in healthy older adults. ADPKD severity [eGFR: 73±33 ml/min/1.73m2, htTKV: 1104±80 cc/meter] was unrelated to depressive symptoms, although frequent pain (abdominal, back, and/or flank pain experienced at least daily) strongly associated with higher depressive symptom levels. Baseline depressive symptoms did not predict kidney function (eGFR, htTKV) at 36 months, adjusting for baseline measures and confounders.

Conclusions:
Our results reveal a relatively low prevalence of clinically significant depressive symptoms in a large sample of adult patients with ADPKD who were not undergoing renal replacement therapy. However, frequent pain was associated with a greater degree of depressive symptoms, underscoring the importance of adequate pain control. While these findings highlight the resilience of patients with ADPKD, routine mental health screening is recommended, and validated pain assessment tools may provide useful resources to quantify and manage pain in ADPKD.
Порівняння представлень k-мер-даних ДНК для класифікації через нейронні мережі
Authors: Терпіловський Єгор Олександрович 
Published: December 2024

Ключовим завданням геноміки, яке сприяє розумінню генетичних розладів і розробці точної медицини, є класифікація послідовностей ДНК здорових та хворих людей. Потужним інструментом для його вирішення стали нейронні мережі внаслідок своєї здатності моделювати складні шаблони у великих наборах даних. Фундаментальним кроком у цьому процесі стало представлення послідовностей ДНК у вигляді наборів k-мерів, які є підпослідовностями фіксованої довжини k. У статті оцінюються та порівнюються два методи представлення k-мер-даних. Перший використовує двійкове векторне представлення ознак, де кожен можливий k-мер відповідає двійковій ознаці. Це представлення, незважаючи на свою простоту, потребує високовимірних і розріджених векторів ознак, що висуває значні вимоги до пам’яті та потенційної неефективності обчислень. Другий метод базується на структурі Конвея–Бромейджа–Ліндона Lyndon (CBL — Conway–Bromage–Lyndon), яка вводить стисле та динамічне представлення k-мер-даних. Внаслідок використання найменших циклічних обертань, або намиста, метод CBL зменшує надмірність даних і оптимізує їх зберігання. Ці методи проаналізовано за трьома ключовими показниками: пам’ять, обчислювальна ефективність і продуктивність класифікації за допомогою нейронних мереж. Метод CBL демонструє високу ефективність пам’яті шляхом значного зменшення її обсягу, необхідного для зберігання функцій k-мерів. Він також досягає швидшого часу генерації вектора ознак при вирішенні обчислювальних проблем, пов’язаних з підходом бінарного вектора ознак. З погляду точності класифікації метод CBL працює релятивно, з незначними покращеннями в деяких випадках, що підкреслює його здатність ефективно охоплювати значущі ознаки послідовності. Наведено переваги представлення k-мер-даних на основі CBL, що робить його перспективною альтернативою для великомасштабного геномного аналізу, де і пам’ять, і обчислювальні ресурси є критично обмеженими.
Очистка воды от нефтепродуктов сорбентом на основе терморасширенного графита для орошения сельскохозяйственных угодий
Authors: Войташ А.А. , Берестнева Ю.В. , Ракша Е.В. , Савоськин М.В. 
Published: December 2024

В статье представлены исследования возможности применения терморасширенного графита (ТРГ) в качестве сорбента для удаления нерастворимых и малорастворимых нефтепродуктов с водной поверхности, а также сорбции растворенных в воде экотоксикантов. С помощью гравиметрического метода определена сорбционная емкость ТРГ относительно нефти и нефтепродуктов: бензина, керосина, дизельного топлива, машинного масла, вакуумного масла, бензола. Изучена сорбционная способность ТРГ относительно растворенного в воде бензола методом УФ-спектроскопии. Проведен сравнительный анализ сорбционной емкости полученного нами ТРГ и ряда углеродных сорбентов, описанных в отечественной и зарубежной литературе. Показано, что сорбционная способность полученного нами ТРГ сопоставима, а в некоторых случаях и превышает литературные данные. Полученные результаты свидетельствуют о возможности применения полученного ТРГ для ликвидации аварийных разливов нефтепродуктов на поверхность водоемов, очистки сточных вод промышленных предприятий и природных источников, применяемых, в том числе, для орошения сельскохозяйственных угодий.
The article explores the possibility of thermally expanded graphite (TEG) using as a sorbent for removing insoluble and partially soluble petroleum products from water surface. The sorption capacity of TEG in relation to petroleum and petroleum products (gasoline, kerosene, diesel fuel, engine oil, vacuum oil, benzene and phenol) was determinedby the gravimetric method and UV spectroscopy. A comparative sorption capacity analysis of the TEG obtained by us and a number of carbon sorbents described in literature was carried out. It was shown that the sorption capacity of the TEG obtained by us is comparable, and in some cases even exceeds the literature data. The results indicate to the possibility of obtained TEG using for liquidation of emergency spills of petroleum products on the surface of reservoirs, treatment of industrial wastewater and natural water sources, used, inter alia, for irrigation of agricultural grounds.
Влияние возраста посадочного материала на приживаемость саженцев в саду
Authors: Никольская О.А. , Киктева Е.Н. , Солонкин А.В. 
Published: December 2024

В статье рассматриваются результаты трехлетних наблюдений за приживаемостью саженцев косточковых культур в зависимости от возраста посадочного материала. Исследования проводились в условиях Волгоградской области на светло-каштановых почвах. Целью данной работы являлось изучение приживаемости саженцев разных возрастов в условиях сада для научного обоснования выбора возраста посадочного материала, дающего наибольший процент приживаемости растений. По результатам исследований представлены итоги приживаемости растений в саду. Определен оптимальный возраст посадочного материала, при котором зафиксирован наибольший процент прижившихся растений, а также приведены данные биометрических показателей развития саженцев в саду в первый и второй год после посадки. По итогам проведения опыта было выявлено, что однолетние саженцы имеют наиболее высокую и стабильную приживаемость.
The article deals with the three-year observations results of the stone crop seedlings survival rate depending on the age of the planting material. The research was carried in the Volgograd region on light chestnut soils. The seedlings of different ages survival rate studying in the garden conditions for scientific justification of the planting material age choice, which gives the highest percentage of plant survival was the aim of this research. Based on the researchresults, the outcomes of plant survival in the garden are presented. The optimal planting material age, at which recorded the highest percentage of plants that have taken root is determined, as well as data on seedlings development biometric indicators in the garden in the first and second year after planting are provided. Based on the experimentresults, it was found that annual seedlings have the highest and most stable survival rate.
Первый опыт проведения соревнований по полевому описанию и диагностике почв для студентов-экологов Волгоградского государственного университета
Authors: Годиенко О.А. 
Published: December 2024

Статья посвящена подробному анализу за- ключительного дня полевой учебной практики по почвоведению, которая является неотъемлемой частью учебного процесса в подготовке специали- стов экологов-природопользователей. В качестве исследовательской задачи автором была опреде- лена попытка оценить новый метод активного обучения путем наблюдения и анализа. Для при- влечения интереса студентов к более глубокому изучению морфологических свойств почв впервые были проведены соревнования по полевому описа- нию почв. Использовалась методика Буйволовой А.Ю., Прокофьевой Т.В., Курбановой Ф.Г. Регламент международного соревнования был переработан и адаптирован к учебному плану практики студен- тов-экологов первого курса. Работа студентов оценивалась по 100-балльной системе. Несмотря на то, что к максимальному показателю не при- близилась ни одна команда, в целом студенты лучше справились с описанием морфологических свойств почв, чем при традиционной форме прове- дения практики. В результате анализа проведен- ного по итогам соревнований были выявлены как положительные, так и отрицательные моменты нового активного метода обучения. Так, к положи- тельным моментам можно отнести знакомство студентов с новой российской и международной классификациями почв, а также формами описа- ния почвенного профиля. Применение междуна- родной практики использования цветовой шкалы Манселла позволили минимизировать ошибки при определении цвета почвы, которые при традици- онном формате практики встречались достаточ- но часто. Самые большие трудности у студентов как в процессе применения нового метода обучения, так и при традиционном формате вызвало опреде- ление структуры почвы, поскольку в большинстве методических учебных пособий по проведению пра- ктик по почвоведению отсутствуют иллюстра- тивные примеры различных почвенных структур и отдельностей, а лишь их текстовое описание или графические рисунки. В заключении автор фиксиру- ет, что в таких соревнованиях участники проявля- ют персональную ответственность за конечный общий результат. Также автором предлагается возможность использования в учебном процессе не- имитационных методов. Полученный опыт в при- менении нового метода обучения при прохождении полевой учебной практики по почвоведению, несом- ненно, будет интересен специалистам в области педагогики, преподающим естественнонаучные дисциплины.
The article is devoted to the detailed analysis of the field training practice final day in soil science, which is an integral part of the educational process in training specialists of ecologists and nature managers. As a research task, the author has identified an attempt to evaluate a new method of active learning through observation and analysis. In order to cause students’ interest tofurthersoils morphological properties study, the first competition on field soils description was held.
OPTIMIZING WIND POWER PLANTS: COMPARATIVE ENHANCEMENT IN LOW WIND SPEED ENVIRONMENTS
Authors: Ibrahim Mustafa Hussein , Ibrahim Muhammed A. , Khather Salam Ibrahim 
Published: December 2024

The study aims to optimize wind farm efficiency in low wind speed regions using the HOMER Pro tool to examine the impact of wind turbine ratings on overall efficiency of wind farms. boosting wind farm efficiency is essential for improving economic viability and grid integration. We propose the establishment of three wind farms, each possessing equal capacities but different in individual turbine capacities 1.5 kW, 3.4 kW and 5.1 kW, then optimize their performance in simulation environment. Through employing HOMER Pro optimization algorithm, we assess all wind farms over the period of one year, taking into account wind speed, temperature and geospatial coordinates. Although all wind farms have equal total capacities, simulation results revealed disparities in their generation abilities, reaching up to 22%, favouring the farm with smaller turbines. Furthermore, the results demonstrated that as wind speed decreases, the disparity in power generation between wind farms increases, reaching 51.9% in November, the month with the lowest wind speeds. These findings provide a comprehensive understanding of wind farm behaviour, particularly regarding turbine sizes, and contribute to the research community's efforts to enhance wind farm power production in low wind speed regions. They also help find solutions to enable the embrace of wind energy and decrease fossil fuel consumption in such regions, fulfilling their international sustainability commitments.