bluuebunny/crossref_metadata_2025 huggingface dataset:
ІНФОРМАТИЗАЦІЯ ОСВІТНЬОГО ПРОЦЕСУ В ЗАКЛАДАХ ВИЩОЇ ОСВІТИ ЯК СИСТЕМА
Authors: Кільдеров Дмитро , Микола Микола , Приходько Юрій
Published: July 2023

В статті обґрунтовуються основи інформатизації освітнього процесу в закладах вищої освіти як системи. Розглядаються основні проблеми, дефініції інформатизації освіти. Обгрунтовуються: дидактичні складові, закономірності, основоположні принципи інформатизації освітнього процесу, що характеризують його загальну практичну спрямованість. Визначаються основні системоутворюючі чинники інформатизації освіти з такими функціями: цілепокладання, правова, освітня, психологічна, наукова, інтеграційна, інноваційна, управлінська. Показується комплексність, багатоаспектність проблеми інформатизації освіти, пов’язаність її з вирішенням низки методологічних, правових, організаційних, методичних, програмних, матеріально-технічних задач.
СТАНДАРТИ НАТО ЩОДО ЗАБЕЗПЕЧЕННЯ ЯКОСТІ ПРОФЕСІЙНОЇ ВІЙСЬКОВОЇ ОСВІТИ
Authors: Шабатіна Надія
Published: July 2023

Проведено аналіз стандартів НАТО щодо забезпечення якості професійної військової освіти. Розглянуто принципи і стандарти НАТО, які забезпечують набуття спроможностей щодо надання якісних освітніх послуг у системі військової та професійної військової освіти. Окрему увагу приділено загальним питанням розвитку системи зовнішнього оцінювання якості професійної військової освіти, зокрема проведення інституційного аудиту та акредитації освітніх програм професійної військової освіти, механізмам акредитації, які передбачають використання програмного та інституційного оцінювання. На основі аналізу стандартів НАТО у сфері забезпечення якості військової освіти можна зробити висновок, що західні ЗВО вводять суворі академічні програми, які доповнюють військовий компонент підготовки офіцерів. Заклади військової освіти НАТО приймають цивільні стандарти для розробки академічних програм і курсів, впроваджують відповідні структури управління військовою освітою у рамках програм підготовки офіцерів, а також спрямовані на забезпечення якості військової та професійної військової освіти.
НОРМАТИВНО-ПРАВОВЕ ЗАБЕЗПЕЧЕННЯ ВОЄННОЇ НАУКИ: СТАН ТА НАПРЯМИ ВДОСКОНАЛЕННЯ
Authors: Орда Михайло , Горбачевський Сергій , Кітура Олег , Левицька Лариса
Published: July 2023

Досліджено питання нормативно-правового забезпечення воєнної науки, розглянуто його сучасний стан та напрями подальшого вдосконалення, гармонізовані із сучасними підходами у державах – членах НАТО.
Could Robot Judges Believe? Epistemic Ambitions of the Criminal Trial as we approach the Digital Age
Authors: Gless Sabine
Published: July 2023

Criminal proof is unique, in that it must be able to account for the justification of both: accurate fact-finding and a fair trial. This is Sarah Summers’ main message in her article on the epistemic ambitions of the criminal trial, which focusses on belief as a sort of proxy for societal acceptance of truth as a set of facts established by compliance to procedural rules. This commentary tests her finding by scrutinizing whether it is conceivable that robots, complying to all rules, assist in fact-finding with a specific form of legal belief based on a sophisticated probability weighting opaque to humans. The result is in accordance with Sarah Summers: as long as robots cannot explain their beliefs, any criminal proof based on them flounders as it can neither be part of a fair trial nor ensure acceptance in the existing institutional framework.
Michele Taruffo: pensamiento y evolución de los estudios sobre la prueba
Authors: Passanante Luca
Published: July 2023

El artículo recorre algunas etapas de la vida académica y personal de Michele Taruffo, así como el desarrollo de su pensamiento y de sus estudios sobre la prueba de los hechos en el proceso. El trabajo tiene como objetivo principal ilustrar los puntos centrales de la visión de Taruffo en torno a las complejas y controvertidas relaciones entre proceso, prueba, probabilidad y verdad. De esta manera, se intenta además situar la figura del Maestro en el panorama académico más amplio de colegas y amigos, con los que ha compartido intercambios científicos y experiencias de vida.
Faktor Risiko Kejadian Hemoroid pada Pekerja Usia Produktif
Authors: Widowati Felisitas Sinta , Ernawati Ernawati
Published: July 2023

Hemoroid merupakan salah satu penyakit rektum yang disebabkan oleh pembesaran serta inflamasi vena pada dubur yang bersumber dari hemorrhoidal plexus. Insiden penyakit hemoroid pada pekerja di Indonesia masih tinggi dengan berbagai faktor risikonya. Oleh sebab itu tujuan penelitian ini adalah untuk mengetahui hubungan berbagai faktor risiko dengan kejadian hemoroid pada pekerja usia produktif di perusahaan pra beton Indonesia. Penelitian dilakukan menggunakan metode observasional analitik dengan desain studi cross-sectional. Pengambilan data dengan pengisian kuesioner yang memenuhi kriteria inklusi. Hasil penelitian ini menemukan bahwa jumlah pekerja yang mengalami hemoroid sebanyak 30 responden (21,89%) dari 137 pekerja. Berdasarkan uji statistik, didapatkan tiga faktor risiko yang berhubungan dengan kejadian hemoroid yaitu konstipasi (nilai p = 0,000), keturunan (nilai p = 0,002), dan pola buang air besar (nilai p = 0,002). Sedangkan faktor yang tidak berhubungan yaitu konsumsi serat, usia, lama duduk, hubungan seks, pemasukan cairan, dan aktivitas fisik, nilai p > 0,05. Konsumsi serat, usia, lama duduk, pemasukan cairan, dan aktivitas fisik menunjukkan risiko >1 kali untuk terjadinya hemoroid. Konstipasi, keturunan, dan hubungan seks menunjukkan risiko >3 kali untuk terjadinya hemoroid. Pola buang air besar menunjukkan risiko >4 kali untuk terjadinya hemoroid. Kesimpulan yang didapat dari penelitian ini adalah kejadian hemoroid di Perusahaan Pra Beton Indonesia dipengaruhi oleh konstipasi, keturunan, dan pola buang air besar.
Theoretical and methodological aspects of sustainable development management of agricultural enterprises
Authors: Nadvodniuk O.
Published: July 2023

The article systematizes theoretical and methodological approaches to managing the sustainable development of agricultural enterprises and substantiates the need to form a new management model, the main goal of which is the creation of values. It is highlighted that the sustainable development of the enterprise can be defined as its ability to maintain competitiveness, profitability or break-even based on making effective management decisions. It is argued that the management of the sustainable development of the enterprise is a purposeful development that ensures the emergence of new opportunities for positive changes at the macro level in the aspect of sustainable development of the economy, ecology and society. It has been proven that the management of the sustainable development of the enterprise should be oriented towards meeting the needs of interested parties in order to achieve economic, social and environmental goals in the long term. It is proposed to consider the concept of managing the sustainable development of an agricultural enterprise as an abstract model designed to characterize organizational and economic relations formed in society at various levels of the economic system, in the process of interaction of interested parties to achieve the goals of long-term development. It is substantiated that with such an approach to the definition of managing the sustainable development of rural enterprise, due to the rational use of production resources, it will contribute to obtaining a high amount of added value, which is distributed within the social strata of the population, ensuring the balance of all spheres of the internal and external environment in terms of coordinating the interests of stakeholders in the early period. The main approaches to managing the sustainable development of the enterprise from the standpoint of the concept of corporate social responsibility have been supplemented, and the social, environmental, and economic aspects of management based on the principles of corporate social responsibility have been highlighted, which will allow the corporate structure to have a multiplier effect. It is indicated that the economic effect at the level of an agricultural enterprise is provided by its ability to create conditions for increasing economic indicators and the purchasing power of the rural population; social - the ability to ensure the improvement of the welfare of the rural population and workers (safety, health care, education), optimal distribution within social strata; ecological - the ability to preserve the main functions of the environment over a long period of time in the aspect of resource provision, waste collection and their use.
Key words: sustainable development, social corporate responsibility, management of sustainable development, agricultural enterprise.
Theoretical principles of the functioning of the social infrastructure of rural areas
Authors: Golovashenko Yu.
Published: July 2023

The article examines the theoretical aspects of the functioning of the social infrastructure of rural areas and systematizes the peculiarities of its functioning in modern conditions. It is argued that the state of rural social infrastructure is currently satisfactory and does not contribute to the formation of suitable living and working conditions for the rural population. As a result, a conclusion was made about the need for a comprehensive study of the functioning and development of rural social infrastructure and the development of a set of measures for its improvement in the conditions of the post-war period of the country. The important role of social infrastructure in ensuring the sustainable development of rural areas and agriculture has been proven, that in the conditions of war and the complicated post-war period, there will be a need for scientific developments regarding the improvement and restoration of social infrastructure objects in the direction of improving the living conditions of the rural population and strengthening the social capital of rural territory Approaches to the definition of social infrastructure are systematized and a conclusion is drawn that this category cannot be equated with the "social sphere". It is highlighted that in the evolutionary development of the essence of the economic category "social infrastructure of rural areas" there was a transformation of the understanding of the goals of social infrastructure - from the formation of the necessary living conditions of the population to ensuring the reproduction of man and society. It is presented that the purpose of the functioning of the social infrastructure is to create a comfortable environment aimed at improving the living conditions, lifestyle and activities of the rural population, ensuring its physical, intellectual and spiritual development. It has been proven that the rural social infrastructure is organized on the basis of an organic combination of territorial and sectoral principles, but it is not focused on a specialized sectoral consumer, but on a territorial one, i.e. the rural population. It is proposed to consider the definition of rural social infrastructure as a category based on numerous functions and taking into account their impact on the national economy of the country. The main functions of the social purpose infrastructure of the village and their impact on the achievement of sustainable development of agriculture and rural areas are considered. The author's definition of the category "social infrastructure of rural areas" is proposed as a complete system of interconnected links and elements of the rural economy (institutions, enterprises, industries and types of activities), which contributes to the socio-economic development of the territory, as well as ensures human life and affects its quality life through the satisfaction of needs.
Key words: social infrastructure, rural areas, social sphere, elements of social infrastructure, management of social infrastructure development.
Các yếu tố ảnh hưởng đến tính minh bạch thông tin báo cáo tài chính của các công ty niêm yết
Authors: Nguyễn Thị Ái Liên , Đào Thị Mai Anh , Trần Hà Anh , Nguyễn Thu Hà
Published: July 2023

Nghiên cứu này nhằm xác định các yếu tố ảnh hưởng đến minh bạch thông tin báo cáo tài chính của các công ty niêm yết trên Sở giao dịch chứng khoán Hà Nội và Sở giao dịch chứng khoán Thành phố Hồ Chí Minh. Nghiên cứu đã tính toán chỉ số minh bạch thông tin báo cáo tài chính với 53 tiêu chí dựa trên thông tin báo cáo tài chính của 450 doanh nghiệp. Bằng phương pháp hồi quy bình phương tối thiểu, kết quả nghiên cứu cho thấy các nhân tố như quy mô công ty, đòn bẩy tài chính, lợi nhuận, hiệu suất sử dụng tài sản, tỷ lệ sở hữu của cổ đông nước ngoài, công ty kiểm toán, chuẩn mực kế toán quốc tế, địa điểm niêm yết có ảnh hưởng đến mức độ minh bạch thông tin báo cáo tài chính của công ty niêm yết. Từ đó, nghiên cứu đề xuất một số kiến nghị nhằm nâng cao tính minh bạch thông tin, góp phần khơi thông tiềm năng đầu tư và phát triển bền vững thị trường chứng khoán Việt Nam.
Antihypertensive, Ameliorating Effect on Lipid Profile and Oxidative Stress Markers of Aqueous Extract of Pleurotus floridanus in Rats
Authors: Ines CHIEGUEN TCHIEGUEN , Alain Bertrand DONGMO , Audrey Judith MBANG MBARGA , Jacquy Joyce KOJOM WANCHE , Rodolphe DJESSISSEM , Kevine FANDIO MOUBE , Cunegonde Blanche ETOUNDI OMGBA
Published: July 2023

Context: Hypertension is a silent disease whose prevalence is constantly increasing. Its management is not always controlled. Thus, the objective of this work was to study the antihypertensive effect of the aqueous extract of the edible mushroom Pleurotus floridanus on the lipid profile and some markers of oxidative stress in Wistar rats. Methods: Phytochemical screening and the study of toxicity of the aqueous extract of Pleurotus floridanus were previously performed. The antihypertensive effect of the aqueous extract of Pleurotus floridanus (1000 mg/Kg of BW) was evaluated on Wistar rats, by co-administration of L-NAME (25 mg/Kg of BW) for three weeks. Hemodynamic parameters were measured once a week via the CODA system. Serum parameters such as lipid profile and oxidative stress markers (MDA, catalase, SOD) were evaluated. Results: The results showed that the aqueous extract of Pleurotus floridanus contained tannins, phenols, coumarins, flavonoids, glycosides, steroids and terpenoids and had no particular signs of toxicity. Co-administration of the aqueous extract and L-NAME in the test group resulted, as in the standard (captopril) group, in a moderate increase in systolic, diastolic and mean arterial blood pressure, significantly lower (P < 0.05) than that observed in the positive controls. Also, a significant decrease (P < 0.05) in heart rate during the last two weeks of treatment was observed in the test group. The administration of the aqueous extract regulated the lipid profile and serum stress markers like the reference drug. Conclusion: These results demonstrate the antihypertensive potential of the edible mushroom Pleurotus floridanus.
Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity
Authors: Kim Hong-Kyu , Bae Sung-Jin , Lee Min Jung , Kim Eun Hee , Park Hana , Kim Hwi Seung , Cho Yun Kyung , Jung Chang Hee , Lee Woo Je , Choe Jaewon
Published: July 2023

Background/Aims: To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis.Methods: This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography.Results: Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors.Conclusions: In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.
Mengatasi Permasalahan Pembelajaran Pendidikan Agama Islam Di Sekolah Umum
Authors: Puspita Fulan
Published: July 2023

This paper is background by the existence of Islamic Religious Education teachersin public schools who have a fundamental problem in the implementation ofIslamic Religion education, namely the lack of time to study Islamic Educationsubjects. This then requires the best solution so that the objectives of learning PAIin public schools can be achieved. The research method used is a qualitativelibrary research approach. The results of this paper found that to overcome the lack of PAI study hoursin schools, PAI teachers must innovate learning by using various approaches suchas the faith approach, the habituation approach, and the emotional approach. Allthree must be used to achieve learning objectives and students at school canpractice directly at school
Assistive robotic hand with bi-directional soft actuator for hand impaired patients
Authors: Heung Kelvin H. L. , Li Heng , Wong Thomson. W. L. , Ng Shamay S. M.
Published: July 2023

Soft wearable robotic hand can assist with hand function for the performance of activities of daily living (ADL). However, existing robotic hands lack a mathematical way to quantify the grip force generated for better controlling the grasp of objects during the performance of ADL. To address this issue, this article presents a soft wearable robotic hand with active control of finger flexion and extension through an elastomeric-based bi-directional soft actuator. This actuator bends and extends by pneumatic actuation at lower air pressure, and a flex sensor embedded inside the actuator measures the angles of the fingers in real-time. Analytical models are established to quantify the kinematic and tip force for gripping of the actuator in terms of the relationship between the input pressure and the bending angle, as well as the output force, and are validated experimentally and by the finite element method. Furthermore, the ability of the soft robotic hand to grasp objects is validated with and without being worn on a human hand. The robotic hand facilitates hand opening and closing by the wearer and successfully assists with grasping objects with sufficient force for ADL-related tasks, and the grip force provided by the actuator is further estimated by the analytical models on two healthy subjects. Results suggest the possibility of the soft robotic hand in providing controllable grip strength in rehabilitation and ADL assistance.
Interferon alpha and beta receptor 1 knockout in human embryonic kidney 293 cells enhances the production efficiency of proteins or adenoviral vectors related to type I interferons
Authors: Kim Aro , Park Jong-Hyeon , Lee Min Ja , Kim Su-Mi
Published: July 2023

Human embryonic kidney (HEK) 293 cells are widely used in protein and viral vector production owing to their high transfection efficiency, rapid growth, and suspension growth capability. Given their antiviral, anticancer, and immune-enhancing effects, type I interferons (IFNs) have been used to prevent and treat human and animal diseases. However, the binding of type I IFNs to the IFN-α and-β receptor (IFNAR) stimulates the expression of IFN-stimulated genes (ISGs). This phenomenon induces an antiviral state and promotes apoptosis in cells, thereby impeding protein or viral vector production. In this study, we generated an IFNAR subtype 1 knockout (KO) HEK 293 suspension (IFNAR-KO) cell line by using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) technology. Upon treatment with human IFN-α, the IFNAR-KO cells showed a constant expression of ISGs, including 2ʹ-5ʹ-oligoadenylate synthetase 1 (OAS1), myxovirus resistance 1 (Mx1), protein kinase RNA-activated (PKR), and IFN-induced transmembrane protein 1 (IFITM1), when compared with the wild-type HEK 293 (WT) cells, wherein the ISGs were significantly upregulated. As a result, the titer of recombinant adenovirus expressing porcine IFN-α was significantly higher in the IFNAR-KO cells than in the WT cells. Furthermore, the IFNAR-KO cells continuously produced higher amounts of IFN-α protein than the WT cells. Thus, the CRISPR-Cas9-mediated IFNAR1 KO cell line can improve the production efficiency of proteins or viral vectors related to IFNs. The novel cell line may be used for producing vaccines and elucidating the type I IFN signaling pathway in cells.
Assessment of enzymatically synthesized DNA for gene assembly
Authors: Simmons Brooke L. , McDonald Nathan D. , Robinett Natalie G.
Published: July 2023

Phosphoramidite chemical DNA synthesis technology is utilized for creating de novo ssDNA building blocks and is widely used by commercial vendors. Recent advances in enzymatic DNA synthesis (EDS), including engineered enzymes and reversibly terminated nucleotides, bring EDS technology into competition with traditional chemical methods. In this short study, we evaluate oligos produced using a benchtop EDS instrument alongside chemically produced commercial oligonucleotides to assemble a synthetic gene encoding green fluorescent protein (GFP). While enzymatic synthesis produced lower concentrations of individual oligonucleotides, these were available in half the time of commercially produced oligonucleotides and were sufficient to assemble functional GFP sequences without producing hazardous organic chemical waste.
Association of the use of psychotropic drugs with hospitalization, cardiovascular events, and mortality in patients with type 2 diabetes: a propensity score-matched cohort study
Authors: Hamasaki Hidetaka , Yanai Hidekatsu
Published: July 2023

Background

Use of psychotropic drugs (PD) may be associated with impairment of physical function. However, few studies have assessed the impact of PD on health outcomes in patients with type 2 diabetes. This study aimed to examine the associations between psychotropic drug use and handgrip strength (HGS) and between the use of PD and hospitalization in patients with type 2 diabetes.

Methods

From April 2013 to December 2015, we conducted a retrospective cohort study in patients with type 2 diabetes at the National Center for Global Health and Medicine Kohnodai Hospital. Patients aged 20 years and over who can measure HGS were included. All participants received nutritional guidance regarding diet therapy for type 2 diabetes at baseline. Nonpsychotropic drug users were matched one-to-one with the PD users using propensity score matching method with respect to their baseline covariates. The differences in HGS and the number of patients who had hospitalizations during the study period were examined. By Cox proportional hazard regression analysis, the association between the use of PD and repeated hospitalizations was estimated.

Results

A total of 1,282 patients were enrolled and followed up for 2.36 ± 0.73 years. In the propensity score matching cohort, HGS was significantly lower (p = 0.006) in PD users than non-PD users. PD users had more hospitalizations than non-PD users. Cox proportional hazard regression analysis confirmed the association of repeated hospitalizations with the use of PD (hazard ratio = 2.138; 95% confidence interval, 1.144–3.995, p = 0.017)). In addition, HGS was significantly and inversely correlated with the number of hospitalizations (r = −0.143, p = 0.013).

Conclusions

The use of PD could increase the risk of repeated hospitalizations. Skeletal muscle may play a role in reducing the risk of hospitalization in patients who are treated with PD.
HURP localization in metaphase is the result of a multi-step process requiring its phosphorylation at Ser627 residue
Authors: Didaskalou Stylianos , Efstathiou Christos , Galtsidis Sotirios , Kesisova Ilοna , Halavatyi Aliaksandr , Elmali Tountzai , Tsolou Avgi , Girod Andreas , Koffa Maria
Published: July 2023

Faithful chromosome segregation during cell division requires accurate mitotic spindle formation. As mitosis occurs rapidly within the cell cycle, the proteins involved in mitotic spindle assembly undergo rapid changes, including their interactions with other proteins. The proper localization of the HURP protein on the kinetochore fibers, in close proximity to chromosomes, is crucial for ensuring accurate congression and segregation of chromosomes. In this study, we employ photoactivation and FRAP experiments to investigate the impact of alterations in microtubule flux and phosphorylation of HURP at the Ser627 residue on its dynamics. Furthermore, through immunoprecipitations assays, we demonstrate the interactions of HURP with various proteins, such as TPX2, Aurora A, Eg5, Dynein, Kif5B, and Importin β, in mammalian cells during mitosis. We also find that phosphorylation of HURP at Ser627 regulates its interaction with these partners during mitosis. Our findings suggest that HURP participates in at least two distinct complexes during metaphase to ensure its proper localization in close proximity to chromosomes, thereby promoting the bundling and stabilization of kinetochore fibers.
Insights into structural, spectroscopic, and hydrogen bonding interaction patterns of nicotinamide–oxalic acid (form I) salt by using experimental and theoretical approaches
Authors: Verma Priya , Srivastava Anubha , Tandon Poonam , Shimpi Manishkumar R.
Published: July 2023

In the present work, nicotinamide–oxalic acid (NIC-OXA, form I) salt was crystallized by slow evaporation of an aqueous solution. To understand the molecular structure and spectroscopic properties of NIC after co-crystallization with OXA, experimental infrared (IR), Raman spectroscopic signatures, X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) techniques were used to characterize and validate the salt. The density functional theory (DFT) methodology was adopted to perform all theoretical calculations by using the B3LYP/6-311++G (d, p) functional/basis set. The experimental geometrical parameters were matched in good correlation with the theoretical parameters of the dimer than the monomer, due to the fact of covering the nearest hydrogen bonding interactions present in the crystal structure of the salt. The IR and Raman spectra of the dimer showed the red (downward) shifting and broadening of bands among (N15-H16), (N38-H39), and (C13=O14) bonds of NIC and (C26=O24), (C3=O1), and (C26=O25) groups of OXA, hence involved in the formation of NIC-OXA salt. The atoms in molecules (AIM) analysis revealed that (N8-H9···O24) is the strongest (conventional) intermolecular hydrogen bonding interaction in the dimer model of salt with the maximum value of interaction energy −12.1 kcal mol−1. Furthermore, the natural bond orbital (NBO) analysis of the Fock matrix showed that in the dimer model, the (N8-H9···O24) bond is responsible for the stabilization of the salt with an energy value of 13.44 kcal mol−1. The frontier molecular orbitals (FMOs) analysis showed that NIC-OXA (form I) salt is more reactive and less stable than NIC, as the energy gap of NIC-OXA (form I) salt is less than that of NIC. The global and local reactivity descriptor parameters were calculated for the monomer and dimer models of the salt. The electrophilic, nucleophilic, and neutral reactive sites of NIC, OXA, monomer, and dimer models of salt were visualized by plotting the molecular electrostatic potential (MESP) surface. The study provides valuable insights into combining both experimental and theoretical results that could define the physicochemical properties of molecules.
Novel kinetoplastid-specific cAMP binding proteins identified by RNAi screening for cAMP resistance in Trypanosoma brucei
Authors: Bachmaier Sabine , Gould Matthew K. , Polatoglou Eleni , Omelianczyk Radoslaw , Brennand Ana E. , Aloraini Maha A. , Munday Jane C. , Horn David , Boshart Michael , de Koning Harry P.
Published: July 2023

Cyclic AMP signalling in trypanosomes differs from most eukaryotes due to absence of known cAMP effectors and cAMP independence of PKA. We have previously identified four genes from a genome-wide RNAi screen for resistance to the cAMP phosphodiesterase (PDE) inhibitor NPD-001. The genes were named cAMP Response Protein (CARP) 1 through 4. Here, we report an additional six CARP candidate genes from the original sample, after deep sequencing of the RNA interference target pool retrieved after NPD-001 selection (RIT-seq). The resistance phenotypes were confirmed by individual RNAi knockdown. Highest level of resistance to NPD-001, approximately 17-fold, was seen for knockdown of CARP7 (Tb927.7.4510). CARP1 and CARP11 contain predicted cyclic AMP binding domains and bind cAMP as evidenced by capture and competition on immobilised cAMP. CARP orthologues are strongly enriched in kinetoplastid species, and CARP3 and CARP11 are unique to Trypanosoma. Localization data and/or domain architecture of all CARPs predict association with the T. brucei flagellum. This suggests a crucial role of cAMP in flagellar function, in line with the cell division phenotype caused by high cAMP and the known role of the flagellum for cytokinesis. The CARP collection is a resource for discovery of unusual cAMP pathways and flagellar biology.
Theoretical investigation of catalytic n-butane isomerization over H-SSZ-13
Authors: Spiske Lucas , Plessow Philipp N. , Kazmierczak Kamila , Vandegehuchte Bart D. , Studt Felix
Published: July 2023

Hybrid density functional theory calculations are used to investigate different mechanisms of the isomerization of n-butane to isobutane via intermediate formation of olefins. The monomolecular mechanism for isomerization of butene and isobutene is found to be prevalent, with a Gibbs free energy barrier of 155 kJ/mol at 400°C, compared to the bimolecular mechanism (190 kJ/mol) due to less favorable entropy for the latter. Hydrogen transfer reactions that convert olefins into alkanes (and vice versa) are also included in the investigations, and show a free energy barrier of 203 kJ/mol for conversion of isobutene to isobutane. Additionally, a methyl transfer mechanism is discussed as a possible pathway for formation of C3 and C5 side products, in comparison to the bimolecular mechanism; the highest barrier of the initial methyl transfer is calculated to be 227 kJ/mol. We discuss the influence of entropy and anharmonicity on all mechanisms, stating that through the uncertainties in computational methods when calculating these systems, the calculated reaction barriers are likely to be overestimated here.
A multi-dimensional nomogram to predict non-sentinel lymph node metastases in T1–2HR+ breast cancer
Authors: Xiang Ke , Chen Jialin , Min Yu , Chen Hang , Yang Jiaxin , Hu Daixing , Han Yuling , Yin Guobing , Feng Yang
Published: July 2023

Background

Axillary lymph node dissection (ALND) could be omitted for T1-2 breast cancer patients with 1-2 positive sentinel lymph node (SLN) after breast-conserving surgery when radiation is planned. However, whether ALND could be replaced by radiation in patients with 1-3 positive SLNs when no more non-SLN metastasis were observed after mastectomy are still controversial. The aim of our study was to develop and validate a nomogram for predicting the possibility of non-SLN metastasis in T1–2 and hormone receptor (HR) positive breast cancer patients with 1-3 positive SLNs after mastectomy.

Methods

We retrospectively reviewed and analyzed the data including the basic information, preoperative sonographic characteristics, and pathological features in breast cancer patients with 1-3 positive SLNs in our medical center between Jan 2016 and Dec 2021. The Chi-square, Fisher’s exact test, and t test were used for comparison of categorical and qualitative variables among patients with or without non-SLN metastasis. Univariate and multivariate logistic regression were used to determine the risk factors for non-SLN metastasis. These predictors were used to build the nomogram. The C-index and area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of the model.

Results

A total of 49 in 107 (45.8%) patients were identified with non-SLN metastasis. In multivariate analysis, four variables including younger age, lower estrogen receptor (ER) expression, higher histological score, and cortex thickening of the lymph nodes were determined to be significantly associated with non-SLN metastasis. An individualized nomogram was consequently established with a favorable C-index of 0.822 and verified via two internal validation cohorts.

Conclusions

The current study developed a nomogram predicting non-SLN metastasis for T1–2 and HR+ breast cancer with 1–3 positive SLNs after mastectomy and found that patients in the high-risk group exhibited worse relapse-free survival. The novel nomogram may further help surgeons to determine whether ALND could be omitted when 1-3 positive SLNs were observed in T1–2 and HR+ breast cancer patients.
Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study
Authors: Zhang Lilong , Zi Liuliu , Kuang Tianrui , Wang Kunpeng , Qiu Zhendong , Wu Zhongkai , Liu Li , Liu Rongqiang , Wang Peng , Wang Weixing
Published: July 2023

Objective

There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no studies have explored their causal relationship.

Methods

Instrumental variables of the gut microbiota (N = 13266) and gut microbiota-derived metabolites (N = 7824) were acquired, and a Mendelian randomization study was performed to explore their influence on NAFLD (1483 European cases and 17,781 European controls), ALD (2513 European cases and 332,951 European controls), and viral hepatitis risk (1971 European cases and 340,528 European controls). The main method for examining causality is inverse variance weighting (IVW).

Results

IVW results confirmed that Anaerotruncus (p = 0.0249), Intestinimonas (p = 0.0237), Lachnoclostridium (p = 0.0245), Lachnospiraceae NC2004 group (p = 0.0083), Olsenella (p = 0.0163), and Peptococcus (p = 0.0472) were protective factors for NAFLD, and Ruminococcus 1 (p = 0.0120) was detrimental for NAFLD. The higher abundance of three genera, Lachnospira (p = 0.0388), Desulfovibrio (p = 0.0252), and Ruminococcus torques group (p = 0.0364), was correlated with a lower risk of ALD, while Ruminococcaceae UCG 002 level was associated with a higher risk of ALD (p = 0.0371). The Alistipes (p = 0.0069) and Ruminococcaceae NK4A214 group (p = 0.0195) were related to a higher risk of viral hepatitis. Besides, alanine (p = 0.0076) and phenyllactate (p = 0.0100) were found to be negatively correlated with NAFLD, while stachydrine (Op = 0.0244) was found to be positively associated with NAFLD. The phenylacetate (p = 0.0353) and ursodeoxycholate (p = 0.0144) had a protective effect on ALD, while the threonate (p = 0.0370) exerted a detrimental influence on ALD. The IVW estimates of alanine (p = 0.0408) and cholate (p = 0.0293) showed their suggestive harmful effects against viral hepatitis, while threonate (p = 0.0401) displayed its suggestive protective effect against viral hepatitis.

Conclusion

In conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis.
Migrant orangutan males use social learning to adapt to new habitat after dispersal
Authors: Mörchen Julia , Luhn Frances , Wassmer Olivia , Kunz Julia A. , Kulik Lars , van Noordwijk Maria A. , van Schaik Carel P. , Rianti Puji , Utami Atmoko Sri Suci , Widdig Anja , Schuppli Caroline
Published: July 2023

Dispersal has been suggested to be challenging, especially for species that heavily rely on social learning for knowledge acquisition. One of the obstacles that migrants face is learning how to cope with an unfamiliar, new habitat, which may involve learning from resident individuals. So far, only very few studies have looked at social learning in migrants after dispersal. Here we examine how migrant male orangutans use a behavior called “peering” (an indicator of observational social learning), to learn from local individuals. In total, we analyzed 4,009 daily dyadic associations with and without peering events of 77 males of the highly sociable Sumatran orangutans (Pongo abelii) at the Suaq population and 75 males of the less sociable Bornean orangutans (Pongo pygmaeus wurmbii) at the Tuanan population, covering a combined study time of 30 years. Analysis using generalized linear mixed models supported our prediction that migrant males in Suaq preferentially peered at the local adult females. However, in Tuanan, migrants peered mostly at other adult males and local immatures. Migrants’ peering rates were highest shortly after their arrival, and significantly decreased with increasing time spent in the area. Migrants in both sites peered significantly more at peering targets’ feeding on food items that are rarely eaten within the locals’ diet, than at commonly eaten ones and peered significantly more at skill-intense food items than easy-to-process ones. Further, migrants interacted significantly more with the peered-at food item after the peering event, than before, suggesting that they practice the observed behavior. Our results therefore suggest that migrant males use peering to learn new ecological knowledge after dispersal (e.g., where and what to feed on), and continue to learn complex skills even within adulthood, (e.g., how to feed on skill-intense food items). To do so, migrants selectively attend to the most knowledgeable and/or available individuals, practice the new skill afterwards and even flexibly adjust their learning, e.g., when confronted with intolerant locals or when the need for learning decreases. Together, our study provides important evidence that social learning in great apes expands towards adulthood, an ability which critically impacted also human evolution.
Case report: A novel SON mutation in a Colombian patient with ZTTK syndrome
Authors: Vasquez-Forero Diana Marcela , Masotto Barbara , Ferrer-Avargues Rosario , Moya Christian Martin , Pachajoa Harry
Published: July 2023

Zhu–Tokita–Takenouchi–Kim syndrome is a multisystem disorder resulting from haploinsufficiency in the SON gene, which is characterized by developmental delay/intellectual disability, seizures, facial dysmorphism, short stature, and congenital malformations, primarily in the central nervous system, along with ophthalmic, dental, pulmonary, cardiologic, renal, gastrointestinal, and musculoskeletal anomalies. In this study, we describe the first Colombian patient with ZTT harboring a novel mutation that has not been previously reported and review the clinical and molecular features of previously reported patients in the literature.
RIG-I agonist SLR10 promotes macrophage M1 polarization during influenza virus infection
Authors: Wu Wenxin , Zhang Wei , Alexandar Jeremy S. , Booth J. Leland , Miller Craig A. , Xu Chao , Metcalf Jordan P.
Published: July 2023

Rationale

A family of short synthetic, triphosphorylated stem-loop RNAs (SLRs) have been designed to activate the retinoic-acid-inducible gene I (RIG-I) pathway and induce a potent interferon (IFN) response, which may have therapeutic potential. We investigated immune response modulation by SLR10. We addressed whether RIG-I pathway activation with SLR10 leads to protection of nonsmoking (NS) and cigarette smoke (CS)-exposed mice after influenza A virus (IAV) infection.

Methods

Mice were given 25 µg of SLR10 1 day before IAV infection. We compared the survival rates and host immune responses of NS and CS-exposed mice following challenge with IAV.

Results

SLR10 significantly decreased weight loss and increased survival rates in both NS and CS-exposed mice during IAV infection. SLR10 administration repaired the impaired proinflammatory response in CS-exposed mice without causing more lung injury in NS mice as assessed by physiologic measurements. Although histopathologic study revealed that SLR10 administration was likely to result in higher pathological scores than untreated groups in both NS and CS mice, this change was not enough to increase lung injury evaluated by lung-to-body weight ratio. Both qRT-PCR on lung tissues and multiplex immunoassay on bronchoalveolar lavage fluids (BALFs) showed that most IFNs and proinflammatory cytokines were expressed at lower levels in SLR10-treated NS mice than control-treaded NS mice at day 5 post infection (p.i.). Remarkably, proinflammatory cytokines IL-6, IL-12, and GM-CSF were increased in CS-exposed mice by SLR10 at day 5 p.i. Significantly, SLR10 elevated the ratio of the two chemokines (CXCL9 and CCL17) in BALFs, suggesting macrophages were polarized to classically activated (M1) status. In vitro testing also found that SLR10 not only stimulated human alveolar macrophage polarization to an M1 phenotype, but also reversed cigarette smoke extract (CSE)-induced M2 to M1 polarization.

Conclusions

Our data show that SLR10 administration in mice is protective for both NS and CS-exposed IAV-infected mice. Mechanistically, SLR10 treatment promoted M1 macrophage polarization in the lung during influenza infection. The protective effects by SLR10 may be a promising intervention for therapy for infections with viruses, particularly those with CS-enhanced susceptibility to adverse outcomes.
A unique maternal and placental galectin signature upon SARS-CoV-2 infection suggests galectin-1 as a key alarmin at the maternal–fetal interface
Authors: Zhao Fangqi , Tallarek Ann-Christin , Wang Yiru , Xie Yiran , Diemert Anke , Lu-Culligan Alice , Vijayakumar Pavithra , Kittmann Enrico , Urbschat Christopher , Bayo Juan , Arck Petra C. , Farhadian Shelli F. , Dveksler Gabriela S. , Garcia Mariana G. , Blois Sandra M.
Published: July 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic imposed a risk of infection and disease in pregnant women and neonates. Successful pregnancy requires a fine-tuned regulation of the maternal immune system to accommodate the growing fetus and to protect the mother from infection. Galectins, a family of β-galactoside–binding proteins, modulate immune and inflammatory processes and have been recognized as critical factors in reproductive orchestration, including maternal immune adaptation in pregnancy. Pregnancy-specific glycoprotein 1 (PSG1) is a recently identified gal-1 ligand at the maternal–fetal interface, which may facilitate a successful pregnancy. Several studies suggest that galectins are involved in the immune response in SARS-CoV-2–infected patients. However, the galectins and PSG1 signature upon SARS-CoV-2 infection and vaccination during pregnancy remain unclear. In the present study, we examined the maternal circulating levels of galectins (gal-1, gal-3, gal-7, and gal-9) and PSG1 in pregnant women infected with SARS-CoV-2 before vaccination or uninfected women who were vaccinated against SARS-CoV-2 and correlated their expression with different pregnancy parameters. SARS-CoV-2 infection or vaccination during pregnancy provoked an increase in maternal gal-1 circulating levels. On the other hand, levels of PSG1 were only augmented upon SARS-CoV-2 infection. A healthy pregnancy is associated with a positive correlation between gal-1 concentrations and gal-3 or gal-9; however, no correlation was observed between these lectins during SARS-CoV-2 infection. Transcriptome analysis of the placenta showed that gal-1, gal-3, and several PSG and glycoenzymes responsible for the synthesis of gal-1-binding glycotopes (such as linkage-specific N-acetyl-glucosaminyltransferases (MGATs)) are upregulated in pregnant women infected with SARS-CoV-2. Collectively, our findings identify a dynamically regulated “galectin-specific signature” that accompanies the SARS-CoV-2 infection and vaccination in pregnancy, and they highlight a potentially significant role for gal-1 as a key pregnancy protective alarmin during virus infection.
Interplay between RNA interference and transposable elements in mammals
Authors: Cornec Alexis , Poirier Enzo Z.
Published: July 2023

RNA interference (RNAi) plays pleiotropic roles in animal cells, from the post-transcriptional control of gene expression via the production of micro-RNAs, to the inhibition of RNA virus infection. We discuss here the role of RNAi in regulating the expression of self RNAs, and particularly transposable elements (TEs), which are genomic sequences capable of influencing gene expression and disrupting genome architecture. Dicer proteins act as the entry point of the RNAi pathway by detecting and degrading RNA of TE origin, ultimately leading to TE silencing. RNAi similarly targets cellular RNAs such as repeats transcribed from centrosomes. Dicer proteins are thus nucleic acid sensors that recognize self RNA in the form of double-stranded RNA, and trigger a silencing RNA interference response.
The effect of cytokines on osteoblasts and osteoclasts in bone remodeling in osteoporosis: a review
Authors: Xu Jie , Yu Linxin , Liu Feng , Wan Longbiao , Deng Zhenhua
Published: July 2023

The complicated connections and cross talk between the skeletal system and the immune system are attracting more attention, which is developing into the field of Osteoimmunology. In this field, cytokines that are among osteoblasts and osteoclasts play a critical role in bone remodeling, which is a pathological process in the pathogenesis and development of osteoporosis. Those cytokines include the tumor necrosis factor (TNF) family, the interleukin (IL) family, interferon (IFN), chemokines, and so on, most of which influence the bone microenvironment, osteoblasts, and osteoclasts. This review summarizes the effect of cytokines on osteoblasts and osteoclasts in bone remodeling in osteoporosis, aiming to providing the latest reference to the role of immunology in osteoporosis.