bluuebunny/crossref_metadata_2025 huggingface dataset:
TRANSFORMASI DIGITAL MELALUI INOVASI E-GOVERNMENT PADA PEMERINTAH DAERAH KABUPATEN BUTON SELATAN
Authors: Nastia Nastia
Published: September 2024

The 4.0 and 5.0 era in utilizing technology to improve public services and governance will be a challenge for the government, especially local governments today. Digital transformation for better governance can have an impact on public services, increase citizen engagement, and encourage economic growth. The focus of this research is how digital transformation policies are implemented through the implementation of e-government in the South Buton Regency Regional Government. The observation method is combined with qualitative descriptive analysis. The results show that, compared to other countries, especially in Southeast Asia, Indonesia is still far behind in terms of local government digital transformation. The absence of implementation standardization, inadequate human resources, uneven infrastructure, lack of community involvement, and lack of government commitment are some of the inhibiting factors. The West Java Provincial Government is undergoing digital transformation. One example is the implementation of e-government by the South Buton government. For e-government development to run smoothly, everyone must work together.
Growth and Yield of Mustard (Brassica rapa L.) and Microflora Populations Around the Rhizosphere Due to Urea Fertilizer with Various Biuret Levels
Authors: Sugesti Rahmawita
Published: September 2024

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The Impact of Earthworm Biopore Holes on Groundwater Absorption
Authors: Widyawati Widyawati
Published: September 2024

which is in nature both ossifying and closing ground surface, causes the decline of ground water infiltration. Some efforts to enlarge ground water infiltration have already been done, for example, by making infiltration wells and bioporic infiltration holes. Earthworms naturally do some activities which contribute to make ground water infiltrate. Due to this fact, a research needs conducting on bioporic infiltration holes of earthworms. This research was performed in Sukoharjo, Surakarta from September 2007 up to July 2008. The study aimed to search the diameter and amount of width units of bioporic infiltration holes of earthworms. The number of infiltration holes of earthworms was counted on the basis of measurement plots of 50 cm x 50 cm. The plots, 20 in number, were placed on a piece of land randomly. Each hole of earthworms (biopore) in every plot was measured to find its diameter. The result of the research showed that the average diameter of bioporic infiltration holes of earthworms was 4,58 mm, and there were 20 holes found in every square meter of land. The bioporic infiltration holes of earthworm could extend the infiltration area of ground water as many as 873 times.
Legal Effects Of Fiduciary Guarantee Registration In Online Systems
Authors: Kurniawan Deni , Anggoro Teddy
Published: September 2024

Fiduciary security institutions are regulated through legislation, Act No. 42 of 1999. This law governs the obligation of the registration of fiduciary security in order to provide legal certainty to the interested parties and this fiduciary security registration gives the rights of preference to the fiduciary recipient of other creditors. In 2013, the Government issued a regulation to Administration System of Fiduciary Security Registration electronically in order to improve services to people who need legal services in the field of fiduciary security. Laws of Fiduciary Security are positive law applicable to the fiduciary security, but there are some things that are not regulated in the law, that is, the  registration done with the online system and the legal consequences that are not registered. This study used normative legal research, which explains the existence of the absence of norms in  the Law of Fiduciary Security, i.e. the registration done with the online system and the legal consequences of fiduciary security which are not registered. This study used a source of legal materials consisting of primary, secondary and tertiary legal materials. The results showed that registration of fiduciary security with the online system is regulated through the Regulation of the Minister of Justice and Human Rights of the Republic of Indonesia Number 9  of 2013 concerning the electronic imposition of Fiduciary Security and Regulation of the Minister of Justice and Human Rights of the Republic of Indonesia Number 10 of 2013 concerning the System for Registration of Fiduciary Security done Electronically. The legal consequence of the Agreement of Fiduciary Security which is not registered with the online system is that it does not produce the collateral agreement of the fiduciary security so that the collateral character such as droit de suite and the rights of preference is not inherent in the creditor of the grantor of the fiduciary security and it does not have the executorial power.
Портрет російського дипломата у повсякденному житті його подільського помістя кінця 18 ст.: Аркадій Морков
Authors: Zemskyi Yurii , Mudryk Yurii
Published: September 2024

Мета статті – на життєвому прикладі Аркадія Моркова, одного із чільних російських дипломатів, відтворено зміст характерних рис світоглядно-правового мислення та поведінки представників правлячої еліти росіян у період розширення кордонів імперії кінця 18 ст., у зіткненні зі світоглядними переконаннями і традиціями поведінки представників привілейованих верств у системі європейського політичного простору.
Наукова новизна. На документальних джерелах розкрито особливості поведінки провідних вельмож Російської імперії, котрі, отримавши великі землеволодіння у Подільській губернії, прагнули чимшвидше встановити звичні для російської системи суспільно-політичних відносин порядки, вступаючи через те у непримиренний конфлікт із емансипованим світоглядно-правовим мисленням, звичним для станової еліти і навіть для нижчих верств Українського Правобережжя.
Висновки. Прихильність сучасних росіян до жорстко централізованої системи політичного правління у власній державі значною мірою справедливо обумовлюється історичною спадщиною. Адже питомо російським механізмом, що традиційно лежить в основі побудови та функціонування їхнього соціуму – є принцип абсолютної залежності соціально-політичного успіху/неуспіху всіх осіб (незалежно від щабля розташування в ієрархії) від рівня довіри/недовіри з боку «першої особи», чи то наближеного до «першої особи» довіреного оточення. Водночас, повна залежність навіть «кровно» знатних і впливових сановників від «волі й ласки» «першої особи» компенсується абсолютним зазвичай самовладдям у межах отриманих «за вірну службу» територіальних/адміністративних вотчин.
Така усталена для росіян світоглядно-правова парадигма мислення та поведінка була і залишається категорично неприйнятною й навіть відразною для традиційного європейського середовища, в якому сформувалася, в тому числі, польська та українська національно-світоглядні системи. Оскільки особа, почуваючись вільною – завжди підкреслено шанує власний індивідуалізм і повсякчас прагне забезпечити собі збереження особистої свободи, як головної ознаки людської гідності та честі, а на тому будується також і самоповага.
Київський землеробський синдикат (1894-1919 рр.): основні напрями діяльності для потреб сільського господарства на теренах України
Authors: Chalavan Victor
Published: September 2024

Метою статті є аналіз основних напрямів діяльності Київського землеробського синдикату (1894-1919 рр.), направлених на розвиток сільського господарства та сільськогосподарської промисловості на теренах України.
Наукова новизна дослідження полягає у комплексній оцінці усіх складових діяльності Київського землеробського синдикату для потреб сільського господарства на основі уперше введених до наукового обігу документів.
Висновки. До основних завдань Київського землеробського синдикату, що функціонував у 1894-1919 рр., належало сприяння сільським господарям у придбанні дешевих, але якісних продуктів і предметів вжитку, сільськогосподарських машин і знарядь, а також у збуті на внутрішніх і зовнішніх ринках вироблених господарствами товарів без послуг посередників.
Поряд із функціями посередництва та постачання перед синдикатом стояла низка важливих науково-практичних завдань: влаштування лабораторій і дослідних станцій з метою допомоги як своїм членам, так і розвитку сільського господарства регіону. Київському землеробському синдикату, поряд з низкою фахових сільськогосподарських товариств та інших об’єднань, належить вагома заслуга в організаційному забезпеченні розвитку контрольно-насіннєвої справи на теренах України у кінці 19 – на початку 20 ст.
Створення у 1897 р. Київської контрольної насіннєвої станції і хімічної лабораторії за підтримки синдикату сприяло системним науковим дослідженням якості посівного насіння й інших продуктів сільськогосподарського виробництва. У науковій літературі утвердилася думка, що станція та лабораторія, незмінно очолювані відомими вченими-аграріями П.Р. Сльозкіним (1897-1900), С.Л. Франкфуртом (1900-1913) і В.В. Задлером (1913-1919), стали центрами контрольно-насіннєвої справи для цукробурякового виробництва Південно-Західного регіону Російської імперії, започаткувавши теоретично, методично та практично новий напрям у вітчизняному насінництві – контроль якості насіннєвого матеріалу.
Ентомологічна станція, заснована при Київському землеробському синдикаті у 1903 р. (у подальшому – «Станція по боротьбі зі шкідниками рослин»), стала першою у Російській імперії установою подібного типу, завдячуючи діяльності видатного зоолога-ентомолога В.П. Поспєлова. Станція здійснила вагомий внесок у справу захисту сільськогосподарських рослин від шкідників.
Proteomics of severe SARS-COV-2 infection and paraquat poisoning in human lung tissue samples: comparison of microbial infected and toxic pulmonary fibrosis
Authors: Min Jiang , Jiaqi Hou , Lihua Lin , Qianqian Chai , Shujuan Wang , Xiang Liu , Liang Liu , Liang Ren , Yiwu Zhou , Qian Liu
Published: September 2024

Introduction

Pulmonary fibrosis (PF) encompasses a spectrum of lung conditions characterized by the abnormal accumulation of scar tissue in the lungs, leading to impaired respiratory function. Various conditions can result in severe PF, among which viral infections have emerged as significant triggers. In addition to viral infections, exposure to toxic substances such as paraquat represents another significant risk factor for PF. Therefore, this study aimed to explore the dissimilarities and similarities between PF triggered by viral infections and chemical toxicants, using the mechanism of PF in IPF as a reference.

Methods

Data-independent acquisition proteomics technology was employed to identify COVID-19 and paraquat-induced PF from the autopsy of lung tissue samples obtained from individuals who died due to PF. Bioinformatics was employed for differential protein analysis, and selected indicators were validated on pathological sections.

Results

Our results showed that the differential proteins associated with the two causes of PF were enriched in similar lung fibrosis-related signaling pathways, such as the Wnt signaling pathway. However, differences were observed in proteins such as CACYBP, we verified the consistency of the results with proteomics using the IHC approach

Conclusion

This study illuminates distinct protein-level differences by investigating pulmonary fibrosis pathways in severe COVID-19 and paraquat poisoning. Although both conditions activate lung-protective and repair pathways, COVID-19 shows limited phosphorylation-independent ubiquitination of β-catenin compared to paraquat toxicity. These findings shed light on potential therapeutic targets for PF induced via diverse factors.
Differences in cardiovascular risk factors associated with sex and gender identity, but not gender expression, in young, healthy cisgender adults
Authors: Williams Jennifer S. , Wiley Elise , Cheng Jem L. , Stone Jenna C. , Bostad William , Cherubini Joshua M. , Gibala Martin J. , Tang Ada , MacDonald Maureen J.
Published: September 2024

Background

Sex differences exist in cardiovascular disease risk factors including elevated blood pressure and arterial stiffness, and decreased endothelial function in males compared to females. Feminine gender expression may be associated with elevated risk of acute coronary syndrome. However, no study has investigated the associations between sex, gender identity, and gender expression and cardiovascular disease risk factors in young adults.

Methods

One hundred and thirty participants (22 ± 3 years) underwent assessments of hemodynamics, arterial stiffness [pulse wave velocity (PWV)], and brachial artery endothelial function (flow-mediated dilation; %FMD). Participants completed a questionnaire capturing sex category (50 male/80 female), gender identity category (49 men/79 women/2 non-binary), and aspects of gender expression assessed by the Bem Sex Role Inventory-30 (39 androgynous/33 feminine/29 masculine/29 undifferentiated). Sex/gender identity category groups were compared using unpaired t-tests and gender expression groups compared using one-way ANOVAs.

Results

Resting systolic and mean arterial pressure (p < 0.01) were elevated in males vs. females. Central PWV was elevated in males [median (interquartile range): 6.4 (1.8) vs. 5.8 (2.2) m/s, p = 0.02]; however, leg and arm PWV were not different between sexes. %FMD was elevated in males vs. females, after accounting for a larger baseline artery diameter in males (8.8 ± 3.3% vs. 7.2 ± 3.1%, p = 0.02); since the majority of participants were cisgender, the same results were found examining gender identity (men vs. women). There were no differences across gender expression groups (p > 0.05).

Conclusions

Sex/gender identity category, but not gender expression, influence cardiovascular risk factors (blood pressure, arterial stiffness, endothelial function) in cisgender adults; further research is needed in gender-diverse populations.
Genesis of Permian granitoids in the southeast of Inner Mongolia and their response to the Xing’an-Mongolia orogenic belt evolution: constraints from zircon U-Pb age, geochemistry and Hf isotopes
Authors: Xue Xiaogang , Zhang Peng , Chen Guoqiang , Zhang Haihong , Zhang Xuebin
Published: September 2024

Research on the geological process of the Xing’an - Mongolia Orogenic Belt has attracted the attention of scholars both domestically and internationally. Its genesis and tectonic location may help revealing the geological processes asscoaited with the evolution of the Xing’an - Mongolia Orogenic Belt. This study focuses on the development of the Permian granitic complex in Jielin Ranch, and we conduct systematic geological, petrographic, zircon U-Pb chronology, Hf isotope, and geochemical tracing of rock elements for evidence. The results show that the granitic complex is mainly composed of monzogranite and syenogranite, which obtained zircon U-Pb ages of 291.1 ± 1.1 Ma and 260.8 ± 1.1 Ma, respectively. The monzogranite and syenogranite are all acidic and aluminum rich rocks, and the monzogranite is a potassium rich, high potassium calcium alkaline rock series with relatively low REE content, high degree of fractionation, and insignificant europium anomalies, enriched with LILE (Rb, Th, U, K), deficient elements such as Ba, Sr, Nb, Ti, and P, εHf(t) values are from +4.1 to +7.0 (TDM2=1130–920 Ma). Geochemistry shows that the monzogranite belongs to high fractionation of I-type granite, which formed in a subduction-compressional or extension tectonic environment, and Middle Neoproterozoic lower crust rocks as the major source material of magma. The syenogranite is a potassium high potassium transitional rock series with a high rare earth content (214 × 10−6∼325 × 10−6), low LREE/HREE (2.54–6.41), δEu (0.04–0.15) and the typical “four component effect” fractionation mode is enriched in large ion lithophilic elements such as Rb, Th, K, and strongly depleted in elements such as Ba, Sr, Nb, Ta, Ti, P, εHf(t) values are from +4.2 to +8.6 (TDM2=738–1228 Ma), suggesting the characteristics of an “A2 type” granite. The magma originated from partial melting of the lower crust of the Middle and Neoproterozoic with the participation of mantle derived melts, and was formed in a back-arc extensional environment. This suggests that the study area experienced a subduction-compressional or extension tectonic environment during the early Permian and a brief backarc extension process in the late Permian.
Detrital zircon U-Pb geochronology of sediments from the Okinawa Trough: implications for sedimentary provenance
Authors: Yang Bao-Ju , Liu Ji-Hua , Wu Yong-Hua
Published: September 2024

In order to distinguish terrestrial material sources in the Okinawa Trough (OT), this study analyzed four surface sediment samples from the northern, middle, and southern parts of the OT using detrital zircon U-Pb age analysis. The detrital zircon age distributions in the northern Okinawa Trough (N-OT) predominantly fall into 1,000−2,300 Ma and 100−600 Ma age groups. In contrast, in the middle Okinawa Trough (M-OT) and southern Okinawa Trough (S-OT), the detrital zircon age groups of 100−600 Ma and 600–1,000 Ma increase significantly, while the age groups of 1,000−2,300 Ma and >2,300 Ma decrease. Detrital zircons from the N-OT primarily originate from the Yellow River and mixed with the Old Yellow River, while those from the M-OT come mainly from the Yellow River, Yangtze Rivers, and East China Sea. And Zhuoshui River maybe a potential source for the M-OT. The detrital zircons from the S-OT are mainly influenced by the Yangtze River, with some effects from the Lanyang River. This study utilizes detrital zircon U-Pb age analysis to gain a better understanding of the terrestrial material sources in various regions of the OT. Most of the zircon grain are coarse, with grain sizes of 40–150 μm long and 30–100 μm wide in the N-OT, smaller in the M-OT and S-OT in this study, which are probably not modern deposits, but the products in the low sea level period of last glaciation mixed with modern sediments. The transport and sedimentation processes reflect the comprehensive influence of sea level change, Kuroshio Current, river input, East Asian monsoon and other factors from last glaciation to present.
Humoral and cellular immune response from first to fourth SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients—a longitudinal cohort study
Authors: Novak Frederik , Nilsson Anna Christine , Christensen Emil Birch , Stougaard Caroline Louise , Barnkob Mike Bogetofte , Holm Dorte K. , Witt Agnes Hauschultz , Byg Keld-Erik , Johansen Isik S. , Nielsen Christian , Sejbaek Tobias
Published: September 2024

Background

This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection.

Methods

Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ T-cells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests.

Results

The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 – 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 – 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response.

Discussion

Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections.
Type V collagen-induced nasal tolerance prevents lung damage in an experimental model: new evidence of autoimmunity to collagen V in COPD
Authors: Robertoni Fabíola Santos Zambon , Velosa Ana Paula Pereira , Oliveira Luana de Mendonça , Almeida Francine Maria de , Silveira Lizandre Keren Ramos da , Queiroz Zelita Aparecida de Jesus , Lobo Thays de Matos , Contini Vitória Elias , Baldavira Camila Machado , Carrasco Solange , Fernezlian Sandra de Morais , Sato Maria Notomi , Capelozzi Vera Luiza , Lopes Fernanda Degobbi Tenorio Quirino dos Santos , Teodoro Walcy Paganelli Rosolia
Published: September 2024

Background

Chronic obstructive pulmonary disease (COPD) has been linked to immune responses to lung-associated self-antigens. Exposure to cigarette smoke (CS), the main cause of COPD, causes chronic lung inflammation, resulting in pulmonary matrix (ECM) damage. This tissue breakdown exposes collagen V (Col V), an antigen typically hidden from the immune system, which could trigger an autoimmune response. Col V autoimmunity has been linked to several lung diseases, and the induction of immune tolerance can mitigate some of these diseases. Evidence suggests that autoimmunity to Col V might also occur in COPD; thus, immunotolerance to Col V could be a novel therapeutic approach.

Objective

The role of autoimmunity against collagen V in COPD development was investigated by analyzing the effects of Col V-induced tolerance on the inflammatory response and lung remodeling in a murine model of CS-induced COPD.

Methods

Male C57BL/6 mice were divided into three groups: one exposed to CS for four weeks, one previously tolerated for Col V and exposed to CS for four weeks, and one kept in clean air for the same period. Then, we proceeded with lung functional and structural evaluation, assessing inflammatory cells in bronchoalveolar lavage fluid (BALF) and inflammatory markers in the lung parenchyma, inflammatory cytokines in lung and spleen homogenates, and T-cell phenotyping in the spleen.

Results

CS exposure altered the structure of elastic and collagen fibers and increased the pro-inflammatory immune response, indicating the presence of COPD. Col V tolerance inhibited the onset of emphysema and prevented structural changes in lung ECM fibers by promoting an immunosuppressive microenvironment in the lung and inducing Treg cell differentiation.

Conclusion

Induction of nasal tolerance to Col V can prevent inflammatory responses and lung remodeling in experimental COPD, suggesting that autoimmunity to Col V plays a role in COPD development.
Adriamycin-induced podocyte injury via the Sema3A/TRPC5/Rac1 pathway
Authors: Liu Yan , Ge Ri-Li , Shan Zhen-Zhen , Wang Yan-Jun , Yang Yan-Yan , Sun Xue , Luo Peng-Li
Published: September 2024

Podocytopathies encompass kidney diseases where direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Although Semaphorin3A (Sema3A) is expressed in podocytes and tubular cells in adult mammalian kidneys and has a common effect on the progression of podocyte injury, its mechanism remains unclear. Previous studies have shown increased Sema3A expression in various glomerulopathies, indicating a gap in understanding its role. In this study, analysis of human data revealed a positive correlation between the levels of urinary Sema3A and Podocalyxin (PCX), suggesting a close relationship between Sema3A and podocyte loss. Furthermore, the impact of Adriamycin on podocytes was investigated. Adriamycin induced podocyte migration and apoptosis, along with an increase in Sema3A expression, all of which were ameliorated by the inhibition of Sema3A. Importantly, TRPC5 was found to increase the overexpression of Sema3A in podocytes. A TRPC5 inhibitor, AC1903, alleviated podocyte migration and apoptosis, inhibiting the formation of lamellar pseudopodia in the podocyte cytoskeleton by lowering the expression of Rac1. Furthermore, AC1903 relieved massive albuminuria and foot process effacement in the kidneys of Adriamycin-treated mice in vivo. In conclusion, our findings suggest that Sema3A may impact the cytoskeletal stability of podocytes through TRPC5 ion channels, mediated by Rac1, ultimately leading to foot process effacement. Notably, AC1903 demonstrates the potential to reverse Adriamycin-induced foot process fusion and urine protein. These results contribute to a deeper understanding of the mechanisms involved in podocytopathies and highlight the therapeutic potential of targeting the Sema3A-TRPC5 pathway.
Machine learning models for predicting risks of MACEs for myocardial infarction patients with different VEGFR2 genotypes
Authors: Kirdeev Alexander , Burkin Konstantin , Vorobev Anton , Zbirovskaya Elena , Lifshits Galina , Nikolaev Konstantin , Zelenskaya Elena , Donnikov Maxim , Kovalenko Lyudmila , Urvantseva Irina , Poptsova Maria
Published: September 2024

Background

The development of prognostic models for the identification of high-risk myocardial infarction (MI) patients is a crucial step toward personalized medicine. Genetic factors are known to be associated with an increased risk of cardiovascular diseases; however, little is known about whether they can be used to predict major adverse cardiac events (MACEs) for MI patients. This study aimed to build a machine learning (ML) model to predict MACEs in MI patients based on clinical, imaging, laboratory, and genetic features and to assess the influence of genetics on the prognostic power of the model.

Methods

We analyzed the data from 218 MI patients admitted to the emergency department at the Surgut District Center for Diagnostics and Cardiovascular Surgery, Russia. Upon admission, standard clinical measurements and imaging data were collected for each patient. Additionally, patients were genotyped for VEGFR-2 variation rs2305948 (C/C, C/T, T/T genotypes with T being the minor risk allele). The study included a 9-year follow-up period during which major ischemic events were recorded. We trained and evaluated various ML models, including Gradient Boosting, Random Forest, Logistic Regression, and AutoML. For feature importance analysis, we applied the sequential feature selection (SFS) and Shapley’s scheme of additive explanation (SHAP) methods.

Results

The CatBoost algorithm, with features selected using the SFS method, showed the best performance on the test cohort, achieving a ROC AUC of 0.813. Feature importance analysis identified the dose of statins as the most important factor, with the VEGFR-2 genotype among the top 5. The other important features are coronary artery lesions (coronary artery stenoses ≥70%), left ventricular (LV) parameters such as lateral LV wall and LV mass, diabetes, type of revascularization (CABG or PCI), and age. We also showed that contributions are additive and that high risk can be determined by cumulative negative effects from different prognostic factors.

Conclusion

Our ML-based approach demonstrated that the VEGFR-2 genotype is associated with an increased risk of MACEs in MI patients. However, the risk can be significantly reduced by high-dose statins and positive factors such as the absence of coronary artery lesions, absence of diabetes, and younger age.
SR9883 is a novel small-molecule enhancer of α4β2* nicotinic acetylcholine receptor signaling that decreases intravenous nicotine self-administration in rats
Authors: Braunscheidel Kevin M. , Voren George , Fowler Christie D. , Lu Qun , Kuryatov Alexander , Cameron Michael D. , Ibañez-Tallon Ines , Lindstrom Jon M. , Kamenecka Theodore M. , Kenny Paul J.
Published: September 2024

Background

Most smokers attempting to quit will quickly relapse to tobacco use even when treated with the most efficacious smoking cessation agents currently available. This highlights the need to develop effective new smoking cessation medications. Evidence suggests that positive allosteric modulators (PAM) and other enhancers of nicotinic acetylcholine receptor (nAChR) signaling could have therapeutic utility as smoking cessation agents.

Methods

3-[3-(3-pyridyl)-1,2,4-oxadiazol-5-yl]benzonitrile (NS9283) was used as a starting point for medical chemistry efforts to develop novel small molecule enhancers of α4β2* nAChR stoichiometries containing a low-affinity agonist binding site at the interface of α4/α4 and α4/α5 subunits.

Results

The NS9283 derivative SR9883 enhanced the effect of nicotine on α4β2* nAChR stoichiometries containing low-affinity agonist binding sites, with EC50 values from 0.2–0.4 μM. SR9883 had no effect on α3β2* or α3β4* nAChRs. SR9883 was bioavailable after intravenous (1 mg kg−1) and oral (10–20 mg kg−1) administration and penetrated into the brain. When administered alone, SR9883 (5–10 mg kg−1) had no effect on locomotor activity or intracranial self-stimulation (ICSS) thresholds in mice. When co-administered with nicotine, SR9883 enhanced locomotor suppression and elevations of ICSS thresholds induced by nicotine. SR9883 (5 and 10 mg kg−1) decreased responding for intravenous nicotine infusions (0.03 mg kg−1 per infusion) but had no effect on responding for food rewards in rats.

Conclusions

These data suggest that SR9883 is useful for investigating behavioral processes regulated by certain α4β2* nAChR stoichiometries. SR9883 and related compounds with favorable drug-like physiochemical and pharmacological properties hold promise as novel treatments of tobacco use disorder.
Prediction of lymphovascular invasion of gastric cancer based on contrast-enhanced computed tomography radiomics
Authors: Zhen Si-Yu , Wei Yong , Song Ran , Liu Xiao-Huan , Li Pei-Ru , Kong Xiang-Yan , Wei Han-Yu , Fan Wen-Hua , Liang Chang-Hua
Published: September 2024

Background

Lymphovascular invasion (LVI) is a significant risk factor for lymph node metastasis in gastric cancer (GC) and is closely related to the prognosis and recurrence of GC. This study aimed to establish clinical models, radiomics models and combination models for the diagnosis of GC vascular invasion.

Methods

This study enrolled 146 patients with GC proved by pathology and who underwent radical resection of GC. The patients were assigned to the training and validation cohorts. A total of 1,702 radiomic features were extracted from contrast-enhanced computed tomography images of GC. Logistic regression analyses were performed to establish a clinical model, a radiomics model and a combined model. The performance of the predictive models was measured by the receiver operating characteristic (ROC) curve.

Results

In the training cohort, the age of LVI negative (−) patients and LVI positive (+) patients were 62.41 ± 8.41 and 63.76 ± 10.08 years, respectively, and there were more male (n = 63) than female (n = 19) patients in the LVI (+) group. Diameter and differentiation were the independent risk factors for determining LVI (−) and (+). A combined model was found to be relatively highly discriminative based on the area under the ROC curve for both the training (0.853, 95% CI: 0.784–0.920, sensitivity: 0.650 and specificity: 0.907) and the validation cohorts (0.742, 95% CI: 0.559–0.925, sensitivity: 0.736 and specificity: 0.700).

Conclusions

The combined model had the highest diagnostic effectiveness, and the nomogram established by this model had good performance. It can provide a reliable prediction method for individual treatment of LVI in GC before surgery.
Targeted inhibition of BET proteins in HPV16-positive head and neck squamous cell carcinoma reveals heterogeneous transcriptional responses
Authors: Rao Aakarsha , Stosic Milan S. , Mohanty Chitrasen , Suresh Dhruthi , Wang Albert R. , Lee Denis L. , Nickel Kwangok P. , Chandrashekar Darshan S. , Kimple Randall J. , Lambert Paul F. , Kendziorski Christina , Rounge Trine B. , Iyer Gopal
Published: September 2024

Human papillomaviruses (HPV), most commonly HPV16, are associated with a subset of head and neck squamous cell carcinoma (HNSCC) tumors, primarily oropharyngeal carcinomas, with integration of viral genomes into host chromosomes associated with worse survival outcomes. We analyzed TCGA data and found that HPV+ HNSCC expressed higher transcript levels of the bromodomain and extra terminal domain (BET) family of transcriptional coregulators. The role of BET protein-mediated transcription of viral-cellular genes in the viral-HNSCC genomes needs to be better understood. Using a combination of TAME-Seq, qRT-PCR, and immunoblot analyses, we show that BET inhibition downregulates E6 and E7 significantly, with heterogeneity in the downregulation of viral transcription across different HPV+ HNSCC cell lines. Chemical BET inhibition was phenocopied with the knockdown of BRD4, mirroring the downregulation of viral E6 and E7 expression. We found that BET inhibition directly downregulated c-Myc and E2F expression and induced CDKN1A (p21) expression, leading to a G1-cell cycle arrest with apoptotic activity. Overall, our studies demonstrate that BET inhibition regulates both E6 and E7 viral and key cellular cell cycle regulator E2F gene expression and cellular gene expression in HPV-associated HNSCC and highlight the potential of BET inhibitors as a therapeutic strategy for this disease while also underscoring the importance of considering the heterogeneity in cellular responses to BET inhibition.
A nomogram for predicting neonatal apnea: a retrospective analysis based on the MIMIC database
Authors: Huang Huisi , Shi Yanhong , Hong Yinghui , Zhu Lizhen , Li Mengyao , Zhang Yue
Published: September 2024

Introduction

The objective of this study is to develop a model based on indicators in the routine examination of neonates to effectively predict neonatal apnea.

Methods

We retrospectively analysed 8024 newborns from the MIMIC IV database, building logistic regression models and decision tree models. The performance of the model is examined by decision curves, calibration curves and ROC curves. Variables were screened by stepwise logistic regression analysis and LASSO regression.

Results

A total of 7 indicators were ultimately included in the model: gestational age, birth weight, ethnicity, gender, monocytes, lymphocytes and acetaminophen. The mean AUC (the area under the ROC curve) of the 5-fold cross-validation of the logistic regression model in the training set and the AUC in the validation set are 0.879 and 0.865, respectively. The mean AUC (the area under the ROC curve) of the 5-fold cross-validation of the decision tree model in the training set and the AUC in the validation set are 0.861 and 0.850, respectively. The calibration and decision curves in the two cohorts also demonstrated satisfactory predictive performance of the model. However, the logistic regression model performs relatively well.

Discussion

Our results proved that blood indicators were valuable and effective predictors of neonatal apnea, which could provide effective predictive information for medical staff.
Unraveling the nexus of age, epilepsy, and mitochondria: exploring the dynamics of cellular energy and excitability
Authors: Xie Wen , Koppula Sushruta , Kale Mayur B. , Ali Lashin S. , Wankhede Nitu L. , Umare Mohit D. , Upaganlawar Aman B. , Abdeen Ahmed , Ebrahim Elturabi E. , El-Sherbiny Mohamed , Behl Tapan , Shen Bairong , Singla Rajeev K.
Published: September 2024

Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible for energy production and calcium regulation. This review offers an in-depth examination of the interplay between epilepsy, mitochondrial function, and aging. Many factors might account for the correlation between epilepsy and aging. Mitochondria, integral to cellular energy dynamics and neuronal excitability, perform a critical role in the pathophysiology of epilepsy. The mechanisms linking epilepsy and mitochondria are multifaceted, involving mitochondrial dysfunction, reactive oxygen species (ROS), and mitochondrial dynamics. Mitochondrial dysfunction can trigger seizures by compromising ATP production, increasing glutamate release, and altering ion channel function. ROS, natural byproducts of mitochondrial respiration, contribute to oxidative stress and neuroinflammation, critical factors in epileptogenesis. Mitochondrial dynamics govern fusion and fission processes, influence seizure threshold and calcium buffering, and impact seizure propagation. Energy demands during seizures highlight the critical role of mitochondrial ATP generation in maintaining neuronal membrane potential. Mitochondrial calcium handling dynamically modulates neuronal excitability, affecting synaptic transmission and action potential generation. Dysregulated mitochondrial calcium handling is a hallmark of epilepsy, contributing to excitotoxicity. Epigenetic modifications in epilepsy influence mitochondrial function through histone modifications, DNA methylation, and non-coding RNA expression. Potential therapeutic avenues targeting mitochondria in epilepsy include mitochondria-targeted antioxidants, ketogenic diets, and metabolic therapies. The review concludes by outlining future directions in epilepsy research, emphasizing integrative approaches, advancements in mitochondrial research, and ethical considerations. Mitochondria emerge as central players in the complex narrative of epilepsy, offering profound insights and therapeutic potential for this challenging neurological disorder.
A simple two-stage carrier-phase estimation algorithm for 32-QAM coherent optical communication systems
Authors: Peng Min , Wang Xiangqing , Yang Xiaokun , Wang Dongfei
Published: September 2024

The combination of high-order modulation formats and linewidth-tolerant carrier phase estimation (CPE) can effectively improve spectrum efficiency and relax the limitation of laser linewidth. This paper presents a simple two-stage CPE algorithm for polarization-multiplexed (PM) 32-quadrature amplitude modulation (32-QAM) coherent optical communication systems. The algorithm uses an enhanced QPSK partitioning algorithm combined with a simplified 4th power CPE method for coarse estimation in the initial stage and maximum likelihood (ML) detection in the subsequent fine stage. The CPE algorithm significantly increases the number of symbols used in the first stage of coarse estimation. This results in a significant increase in the stability and reliability of the phase estimation, and the CPE algorithm significantly reduces the computational complexity. The optimal parameters, phase estimation performance, and system performance of the algorithm were investigated by building a 22 Gbaud PM 32-QAM coherent system simulation platform and a 5 Gbaud PM 32-QAM coherent system experimental platform. The results show that the proposed two-stage CPE algorithm has a stronger linewidth tolerance difference than the conventional QPSK, and the two-stage CPE algorithm with an optimal block length of 105 performs comparable to blind phase search (BPS). The optical signal noise Ratio (OSNR) value is 21.2 dB and the bit error rate (BER) is 1.8 × 10−3 for the optimal block length of 105. The receiving-end DSP unit with a flexible scheme and good communication performance will have potential applications in adaptive elastic optical networks.
A qualitative investigation on career barriers and career preparation behaviors of third culture kids in south Korean colleges
Authors: Shin Kahyen , Ra Young-An
Published: September 2024

Introduction

The purpose of this study is to explore career experiences of South Korean Third Culture Kids (TCKs) and to examine their career barriers and career preparation behaviors.

Methods

For these aims, eight South Korean TCKs were interviewed and Consensual Qualitative Research (CQR) was used to analyze the interview data.

Results

As results, two domains, career barriers and career preparation behaviors were developed. For career barriers and career preparation behaviors of TCKs, five each core ideas were reported.

Discussion

At the end of the study, we offered discussions and implications for higher education professionals and career counselors. The findings of the present study will contribute to the career development of TCK populations.
The genetic advantage of healthy centenarians: unraveling the central role of NLRP3 in exceptional healthspan
Authors: Verlinden Stef F.
Published: September 2024

Despite extensive research into extending human healthspan (HS) and compressing morbidity, the mechanisms underlying aging remain elusive. However, a better understanding of the genetic advantages responsible for the exceptional HS of healthy centenarians (HC), who live in good physical and mental health for one hundred or more years, could lead to innovative health-extending strategies. This review explores the role of NLRP3, a critical component of innate immunity that significantly impacts aging. It is activated by pathogen-associated signals and self-derived signals that increase with age, leading to low-grade inflammation implicated in age-related diseases. Furthermore, NLRP3 functions upstream in several molecular aging pathways, regulates cellular senescence, and may underlie the robust health observed in HC. By targeting NLRP3, mice exhibit a phenotype akin to that of HC, the HS of monkeys is extended, and aging symptoms are reversed in humans. Thus, targeting NLRP3 could offer a promising approach to extend HS. Additionally, a paradigm shift is proposed. Given that the HS of the broader population is 30 years shorter than that of HC, it is postulated that they suffer from a form of accelerated aging. The term ‘auto-aging’ is suggested to describe accelerated aging driven by NLRP3.
Active Disturbance Rejection Control for the Trajectory Tracking of a Quadrotor
Authors: Ramírez-Neria Mario , Luviano-Juárez Alberto , González-Sierra Jaime , Ramírez-Juárez Rodrigo , Aguerrebere Joaquín , Hernandez-Martinez Eduardo G.
Published: September 2024

In the last decade, quadrotors have gained popularity among industry and academia due to their capabilities and the various applications in which they can be found. In addition to the above, because this is an underactuated system, researchers have found it a great challenge to control. Despite this, there is a wide variety of methodologies in the literature to control this type of system. Based on the above, this work proposed an alternative to trajectory tracking control for quadrotor unmanned aerial vehicles (UAV). The problem was divided into two main control loops: an outer control loop for the position coordinates, tackled through linear active disturbance rejection controllers (ADRC), and an inner control loop related to the orientation variables, addressed via robust proportional-integral-differential (PID) controllers. Furthermore, a generalized proportional integral observer (GPIO) was implemented to estimate the velocity and internal and external disturbances; therefore, the control strategy only depended on the attitude (position and orientation) quadrotor measurements. Then, the control performance was tested through numerical simulations and experimental tests, including wind disturbance inputs.
Microbiological Soil Quality Indicators Associated with Long-Term Agronomical Management of Mediterranean Fruit Orchards
Authors: Arous Aissa , Gargouri Kamel , Palese Assunta Maria , Pane Catello , Scotti Riccardo , Zaccardelli Massimo , Altieri Gessica , Celano Giuseppe
Published: September 2024

Soil microorganisms play a crucial role in maintaining soil fertility sensu lato. Sustainable soil management aims to make the soil environment more hospitable increasing microorganism diversity and complexity by means of the minimal disturbance of soil and inputs of organic material. This results in the effective functioning of agricultural systems, better crop productivity, and a reduction in environmental impacts. A study was carried out to evaluate the effects of the long-term application (more than 15 years) of sustainable practices versus conventional ones on soil microbial biomass activity and its functional diversity within different Mediterranean commercial fruit orchards located in Southern Italy. A preliminary survey—performed using the electromagnetic induction technique (EMI)—guided the collection of representative soil samples by reducing the spatial heterogeneity of soil microorganisms. Soil management practices, based on no tillage and the recycling of organic materials of different origins and quality produced within the orchard, increased soil organic carbon, telluric microorganisms activity and their functional diversity compared to ‘non-conservative’ management methods such as continuous tillage. In addition, the rational use of the orchard-inside organic matter (natural/seeded grass cover and pruning material) allowed it to virtuously transform from useless waste into precious resources, eliminating the logistical and economic constraints for their disposal. The simultaneous use of different types of soil management strategies aimed at soil conservation reinforced the positive effects on the microbiological indicators of soil quality rather than the application of a single strategy. This study provides the opportunity to represent what could be the possible evolution of tilled orchards towards more balanced soil conditions when subjected to conservative practices, offering a reference model for fruit growers and technicians who want to improve the stability and the resiliency of their agrosystems.
Design and Test of Electromagnetic Vibration Type Fine and Small-Amount Seeder for Millet
Authors: Zhang Yanqing , Tang Yaocheng , He Ding , Shi Jie , Hao Lirong , Li Jiabao , Sun Deng , Li Hongbo , Zhang Zhiyong , Ye Shaobo , He Yongqiang , Cui Qingliang
Published: September 2024

To solve the problem of large sowing amount and poor sowing uniformity for millet, according to the physical characteristics of the millet seed and its sowing agronomic requirements, an electromagnetic vibration type fine and small-amount seeder was designed, and the main technical parameters of the seeder were determined, in order to realize the functions of furrow opening, electronically controlled seed metering, soil covering and pressing. Based on the principle of electromagnetic vibration, an electromagnetic vibration type seed metering device was designed to achieve uniform seeding of the millet seed with a small sowing amount; a seeding amount electronic control device was designed using an STM32 microcontroller, which realized the switching to sowing agronomic mode and the adjustment of the seeding amount with sowing operation speed; a vibration experimental bench was set up to simulate the vibration state of field operation, and studies on the seeding performance and vibration damping of the seed metering device by the isolation spring were carried out, as well as field sowing tests for verification. When the working voltage of the seed metering device is 80–160 V, the coefficients of variation for seeding uniformity per row and for total seeding uniformity are not greater than 3.57% and 2.39%, respectively, and the seed damage rate is less than 0.5%. The installation of isolation springs can increase the maximum vibration acceleration of the seed metering device by 10.61–28.20%, significantly reducing the impact of external vibrations on the seed metering device. Within the range of suitable sowing operation speeds, the electronic control device can meet the seeding amounts along with sowing operation speed in the 6, 7.5 and 9 kg/hm2 sowing agronomic modes, and the coefficient of variation for seeding uniformity per row, for total seeding uniformity and for sowing uniformity are not greater than 4.63%, 2.48% and 23.38%, respectively. This study provides a reference for the development of sowing machinery for millet crop.