bluuebunny/crossref_metadata_2025 huggingface dataset:
Kun Young PARK, Letter from Joseon to Korea: International Politics of the Korean Peninsula
Authors: Yildirim Muhammed Eren
Published: December 2024

South Korea has indispensable military relations with the United States (US), especially in the context of its hostile relations with North Korea. In addition, China’s giant economic power makes South Korea reluctant to abandon its relations with China. Yet another significant factor complicating the regional dynamics for South Korea is the unresolved historical issues inherited from the imperial exploitation by the Japanese Empire on the Korean peninsula. This book aims to replace the narrative of South Korea’s as an “agent” in the global arena, considering its historical values and above-mentioned transforming conditions, with a multifaceted approach called “strategic pragmatism.” The author asks the following questions: what resources does South Korea have in its foreign policy-making processes?, what is its strategy based on these resources?, and what are the sources of the fundamental beliefs that construct the policymakers’ perception of South Korea’s foreign policy strategy?
Burnout and Professional Development: A Study of Lithuanian Physiotherapists
Authors: Žlibinaitė Laura , Yucel Hulya
Published: December 2024

Background. Physiotherapists’ qualifications involve treatment, responsibility, and communication, putting them at risk of burnout. This study aimed to evaluate the prevalence of burnout in Lithuanian physiotherapists and its impact on their professional development.
Methods. A total of 133 physiotherapists working both in the public and private sectors completed an anonymous survey between January and March 2024 through an online form linked to www.apklausa.lt. Burnout syndrome was measured using the Copenhagen Burnout Inventory (CBI). Socio-demographics and questions related to professional development were utilized.
Results. Total CBI score was 54.92 (moderate burnout). The overall prevalence of physiotherapists reporting moderate burnout was 50.4% (n=67). Thirteen (9.8%) physiotherapists reported high levels and none had severe burnout. Respondents engaged in relevant scientific literature reading (50.8%) and felt confident in solving patients’ problems (64.4%), focused on enhancing general skills (45.5%), and strongly agreed that physiotherapy seminars contribute to knowledge improvement (51.9%). There was a negative correlation (r = -0.26, p < 0.05), indicating a significant inverse relationship between burnout and professional development.
Conclusions. Lithuanian physiotherapists in our study group experience moderate level burnout syndrome. Despite this, they maintain a positive or neutral attitude towards professional development, actively engage in skill improvement activities, and effectively solve patients’ problems.
Keywords: burnout syndrome; Copenhagen Burnout Inventory; physiotherapist; professional development.
Study on EDTA-assisted
phytoremediation of heavy metal contaminated soil by Portulaca oleracea
Authors: Pandey Khusboo , Kumar Tiwari Kamlesh
Published: December 2024

The removal of heavy metal from the soil is necessary in order to protect the environment. Phytoremediation is a process that uses plants to remove the pollutant and helps in the rehabilitation of damaged sites. In different circumstances, along with phytoremediation, chelating chemicals such as ethylenediaminetetraacetic acid (EDTA) are used to enhance the extraction of heavy metals from soil. Experiments were conducted to evaluate the potential role of Portulaca oleracea in the removal of heavy metals from contaminated soil, and to evaluate the effectiveness of EDTA on the removal of heavy metals by Portulaca oleracea. The results revealed that Portulaca oleracea accumulated 126.11 mg/kg of cadmium and 146.22 mg/kg of copper. Translocation factor (TF) for lead, cadmium, chromium, and copper was < 1, and bioconcentration factor (BCF) for cadmium, lead, chromium, and cooper was 4.254, 6.223, 4.385 and 10.97, respectively. After treatment with 0.1 mg/kg of EDTA, the accumulation of cadmium was 187.8 mg/kg, and the accumulation of copper was 196.2 mg/kg. TF for lead, cadmium, chromium, and cooper was > 1 and BCF for lead was 16.19, cadmium 10.75, chromium 8.141 and cooper 12.37. The accumulation of cadmium and lead after treatment with 0.3 mg/kg of EDTA was 222.49 mg/kg and 181.3 mg/kg, respectively. TF for lead, cadmium, chromium, and cooper was > 1 and BCF for lead was 16.34, cadmium 11.53, chromium 8.647 and cooper 7.005. Therefore, the results showed that 0.1 mg/kg of ETDA was the optimal dose for enhanced accumulation of heavy metals.
Non trivial zeros of the generalized Zeta function
Authors: OUKIL Walid
Published: December 2024

In this paper, the generalized Riemann Zeta function is defined on the right half-plane. In particular, this allows us to prove that for every $\tau\in \mathbb{R}$ there exists at most one point $r\in (0,1)$ such that $|\zeta(r+i\tau) |=0$.
VALUE OF THE COSMOLOGICAL CONSTANT Ʌ FROM THE COSMOLOGICAL EQUATIONS OF THE UNIVERSE. CONNECTION OF THE COSMOLOGICAL CONSTANT Ʌ WITH FUNDAMENTAL PHYSICAL CONSTANTS
Authors: Kosinov Mykola
Published: December 2024

A mathematical method for obtaining the value of the cosmological constant Ʌ from the cosmological equations of the Universe has been found. The method is based on the revealed connection of the cosmological constant Ʌ with fundamental physical constants. The new large scale numbers 10^140, 10^160 and 10^180 obtained from the scaling law allowed us to obtain cosmological equations linking the cosmological constant Ʌ with the fine structure constant "alpha", Planck's constant, the speed of light and the electron constants. The approximate Eddington equation Ʌ≈[(me/αћ)^4][(2Gmp/π)^2] is refined to an exact equation. A large number of new cosmological equations are derived, which include the cosmological constant Ʌ. The value of the constant Ʌ is obtained by different methods: from the finalized Eddington equations; from the coincidence of large numbers; from the cosmological equations of the universe and the speed of light; from the cosmological equations of the universe and Planck's constant; from the experimental value of the Pioneer anomaly; from the Kepler relation for the universe. All methods give the same value of the cosmological constant Ʌ (Ʌ = 1.36285...x 10^(-52) m^(-2) ). The theory based on the law of scaling of large numbers predicts a value of the constant Ʌ close to the experimental one. The accuracy of the calculated value of Ʌ is close to the accuracy of the Newtonian constant of gravitation G. The reason for the large number of equivalent equations that include the cosmological constant Ʌ remains a mystery.
Euler Perfect Box 2nd Way
Authors: Muhammad Taha
Published: December 2024

Euler Perfect Box 2nd Way a, b, c, d, e, f, g ∈ N_+ ⟺ Euler Perfect Box Substitute any value of a, b, c into expressions a^2 + b^2+ c^2, & (a + b+ c)^2 in order to know, which one is a complete square! Example (a+b)^2 = a^2 + 2ab + b^2 (2+3)^2 = 25 & 2^2 +2(2)3 +3^2 = 25, then we know (a+b)^2 & (a^2 + 2ab + b^2) are squares. But a^2 + ab = 2^2 + 2(3) = 10, then we know a^2 + ab is not a square.
The Topology of Subspaces of the Configuration Space of Spatial Hexagons
Authors: Kamiyama Yasuhiko
Published: December 2024

We assume that four bond angles of a spatial hexagon are
. According to the choice of the four bond angles, we define the configuration spaces
,
and
. We determine the topological types of these spaces.
Fodder production in peasant-farmers farms of the Non-Chernozem Zone: scientific support
Authors: Shpakov Anatoly
Published: December 2024

The soil, climate and plant resources of the forest zone of the Russian Federation are most favorable for intensive dairy and meat farming. The total area of agricultural land in the zone is about 43914 thousand hectares, including arable land 28669, hayfields 5692 and pastures 7701. With a total population of 61.5 million, there are 0.71 hectares of agricultural land per person. Such an amount of land resources makes it possible to fully provide the population, including the megacities of Moscow, St. Petersburg, Yekaterinburg with livestock and poultry products, to develop the export potential of the territories. To provide the population of the zone with food standards, it is necessary to produce more than 20 million tons of milk, 4.3 million tons of meat, 16 billion eggs. In solving this problem, an important role belongs to peasant farms, individual entrepreneurs and households of the population [1–5].
Accommodated in the Gallery: Unfreedom in the Early History of Boston’s Old North Church
Authors: Crumley Jaimie , Matthews Catherine , Spence Emily
Published: December 2024

Christ Church in Boston, better known by its nickname, Old North Church, held its first worship service in 1723. Old North is the oldest extant church building in Boston and was the second Church of England parish to form in Puritan Boston. While it is best known as the church where, in April 1775, parishioners hung two steeple lanterns to announce the approach of British troops “by sea” across the Charles River, the church’s records reveal that from its early days, African and Indigenous peoples attended the church and participated in baptisms, marriages, and burials there. The customs of the time segregated seating in English churches by race and social class. Therefore, African and Indigenous members were confined to seating in the church’s gallery (balcony). This separation created a discriminatory geography of space in the churches that functioned as a microcosm of the racialized and classed geography of space throughout colonial Boston. Yet those who were “accommodated in the gallery” used the space as what postcolonial scholar Edward W. Said has called a “rival geography” where they exercised their freedom despite their physical and social constraints. This article asserts that although Old North is known for its contributions to Revolutionary War history, another revolution happened concurrently in the church as African and Indigenous peoples who affiliated with the church used it as a space to forge friendships and deepen their faith during an era of social, political, and economic upheavals. Furthermore, the article asserts the importance of studying the lesser-known histories of the African, Indigenous, and multiracial peoples in Old North’s early history because their stories complicate the mythology surrounding the church and reveal the contradictions of freedom in colonial Boston.
ANALISIS PREDIKSI HARGA SAHAM PT GUDANG GARAM TBK INDONESIA
Authors: Michael Michael , Amrizal Amrizal
Published: December 2024

This research aims to predict PT Gudang Garam Tbk's stock prices using the ARIMA method. Historical daily stock price data were analyzed to detect trends and seasonality. The ARIMA model was developed and tested, demonstrating significant predictive accuracy. Evaluation metrics such as Mean Absolute Error and Root Mean Squared Error were employed for performance assessment. The research contributes to stock price prediction methodologies, offering practical implications for investors and financial analysts. In conclusion, the study establishes a robust foundation for utilizing the ARIMA method in forecasting PT Gudang Garam Tbk's future stock prices.
FUZZY LOGIC UNTUK MENENTUKAN KEPUASAN ANGGOTA SERIKAT TERHADAP KINERJA PENGURUS SERIKAT MENGGUNAKAN METODE MAMDANI
Authors: Nuri Nuri Hidayati , Nopriadi Nopriadi
Published: December 2024

A trade union is an organization founded to protect the rights of every worker.In the world of work, this organization is the most important element of the Union Organization established by workers, by workers and also for workers. Which means that this union organization was founded to foster, protect and also fight for every human being who works in a company. This organization has the aims of being free, independent, open, democratic and responsible. Almost all companies in Indonesia are members of worker or labor union organizations, including the city of Batam which is famous as an industrial city. One of the companies in Batam that is part of a trade union or labor organization and that organization is still active is a company operating in the electronics sector, namely PT TEC INDONESIA. The trade union organization or workers at this company is named SPEE-FSPMI PUK TEC which was founded in 2020 led by Mochamad Mustofa, and secretary Masrial, treasurer Fitri Kurniawati, along with management who have responsibilities in their fields.
Flow-cytometry reveals mitochondrial DNA accumulation in Saccharomyces cerevisiae cells during cell cycle arrest
Authors: Potapenko Elena Yu , Kashko Nataliia D. , Knorre Dmitry A.
Published: December 2024

Mitochondria are semi-autonomous organelles containing their own DNA (mtDNA), which is replicated independently of nuclear DNA (nDNA). While cell cycle arrest halts nDNA replication, mtDNA replication continues. In Saccharomyces cerevisiae, flow cytometry enables semi-quantitative estimation of mtDNA levels by measuring the difference in signals between cells lacking mtDNA and those containing mtDNA. In this study, we used flow cytometry to investigate mtDNA accumulation in yeast cells under G1 and G2 phase cell cycle arrest conditions utilising thermosensitive mutants cdc4-3 and cdc15-2. In line with the previous studies, cell cycle arrest induced a several-fold accumulation of mtDNA in both mutants. The total DNA levels in arrested cells correlated with cell forward scattering, suggesting a relationship between individual cell mtDNA quantity and size. In cell cycle-arrested cells, we observed no correlation between cell size and intercellular mtDNA copy number variability. This implies that as cell size increases during arrest, the mtDNA content remains within a specific limited range for each size class. This observation suggests that mtDNA quantity control mechanisms can function in cell cycle-arrested cells.
Homogenous catalysis of peroxynitrite conversion to nitrate by diaryl selenide: a theoretical investigation of the reaction mechanism
Authors: Xue Yuan , Salmon Carrie , Gogonea Valentin
Published: December 2024

Quenching peroxynitrite (a reactive oxidant species) is a vital process in biological systems and environmental chemistry as it maintains redox balance and mitigates damaging effects in living cells and the environment. In this study, we report a systematic analysis of the mechanism of transforming peroxynitrite into nitrate using diaryl selenide in water. Through quantum mechanical calculations, we investigate the dynamic isomerization of peroxynitrite in a homogeneous catalytic environment. The mapped potential energy surfaces (PESs) generated using various methods in conjunction with different basis sets suggest that the isomerization mechanism includes four major steps: the reaction of peroxynitrite with diaryl selenide via oxygen-bound selenium; selenium oxidation in the presence of an appropriate oxidant; oxygen transfer; and ultimately, the generation of nitrate. The molecular orbital analysis suggests a substituent effect on the aromatic ring of diaryl selenide in this reaction. Changes in both molecular orbitals and electrostatic potential highlight the significance of the electron transfer step in ensuring the progression of this reaction.
New tools to monitor Pseudomonas aeruginosa infection and biofilms in vivo in C. elegans
Authors: Xue Feng , Ragno Martina , Blackburn Sarah A. , Fasseas Michael , Maitra Sushmita , Liang Mingzhi , Rai Subash , Mastroianni Giulia , Tholozan Frederique , Thompson Rachel , Sellars Laura , Hall Rebecca , Saunter Chris , Weinkove David , Ezcurra Marina
Published: December 2024

Introduction

Antimicrobial resistance is a growing health problem. Pseudomonas aeruginosa is a pathogen of major concern because of its multidrug resistance and global threat, especially in health-care settings. The pathogenesis and drug resistance of P. aeruginosa depends on its ability to form biofilms, making infections chronic and untreatable as the biofilm protects against antibiotics and host immunity. A major barrier to developing new antimicrobials is the lack of in vivo biofilm models. Standard microbiological testing is usually performed in vitro using planktonic bacteria, without representation of biofilms, reducing translatability. Here we develop tools to study both infection and biofilm formation by P. aeruginosa in vivo to accelerate development of strategies targeting infection and pathogenic biofilms.

Methods

Biofilms were quantified in vitro using Crystal Violet staining and fluorescence biofilm assays. For in vivo assays, C. elegans were infected with P. aeruginosa strains. Pathogenicity was quantified by measuring healthspan, survival and GFP fluorescence. Healthspan assays were performed using the WormGazerTM automated imaging technology.

Results

Using the nematode Caenorhabditis elegans and P. aeruginosa reporters combined with in vivo imaging we show that fluorescent P. aeruginosa reporters that form biofilms in vitro can be used to visualize tissue infection. Using automated tracking of C. elegans movement, we find that that the timing of this infection corresponds with a decline in health endpoints. In a mutant strain of P. aeruginosa lacking RhlR, a transcription factor that controls quorum sensing and biofilm formation, we find reduced capacity of P. aeruginosa to form biofilms, invade host tissues and negatively impact healthspan and survival.

Discussion

Our findings suggest that RhlR could be a new antimicrobial target to reduce P. aeruginosa biofilms and virulence in vivo and C. elegans could be used to more effectively screen for new drugs to combat antimicrobial resistance.
The potential of the BBNJ clearing house mechanism to enhance knowledge pluralism in marine carbon dioxide removal assessment
Authors: Boettcher Miranda , Brent Kerryn
Published: December 2024

As the global community intensifies efforts to achieve net-zero greenhouse gas emissions, active carbon dioxide removal (CDR) is being planned alongside emission reductions. The open ocean, which already absorbs a substantial portion of anthropogenic carbon dioxide, is increasingly seen as a promising site for various types of marine CDR (mCDR). All of these approaches are in the preliminary stages of development, and many questions remain with regard to their assessment and governance. This paper discusses the potential role of the newly established Agreement on the Conservation and Sustainable Use of Marine Biological Diversity of Areas Beyond National Jurisdiction (BBNJ Agreement) in assessing and governing mCDR. A step-by-step mapping of the various stages of the BBNJ environmental impact assessment process shows that the new Clearing House Mechanism (CHM) could facilitate knowledge pluralism and contribute to the holistic assessment of mCDR proposals. The paper concludes by identifying challenges in operationalizing the CHM and putting forward recommendations to strengthen its capacity for fostering knowledge pluralism in decision-making on mCDR research and implementation.
A new prediction model for sustained ventricular tachycardia in arrhythmogenic cardiomyopathy
Authors: Zhang Baowei , Xie Xin , Yu Jinbo , Wu Yizhang , Zhou Jian , Li Xiaorong , Yang Bing
Published: December 2024

Background

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterized by high risks of sustained ventricular tachycardia (sVT) and sudden cardiac death. Identifying patients with high risk of sVT is crucial for the management of ACM.

Methods

A total of 147 ACM patients were retrospectively enrolled in the observational study and divided into training and validation groups. The least absolute shrinkage and selection operator (LASSO) regression model was employed to identify factors associated with sVT. Subsequently, a nomogram was constructed based on multivariable logistic regression analysis. The performance of the nomogram was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis was conducted to assess the clinical utility of the nomogram.

Results

Seven parameters were incorporated into the nomogram: age, male sex, syncope, heart failure, T wave inversion in precordial leads, left ventricular ejection fraction (LVEF), SDNN level. The AUC of the nomogram to predict the probability of sVT was 0.867 (95% CI, 0.797–0.938) in the training group and 0.815 (95% CI, 0.673–0.958) in the validation group. The calibration curve demonstrated a good consistency between the actual clinical results and the predicted outcomes. Decision curve analysis indicated that the nomogram had higher overall net benefits in predicting sVT.

Conclusion

We have developed and internally validated a new prediction model for sVT in ACM. This model could serve as a valuable tool to accurately identify ACM patients with high risk of sVT.
New isotopic evidence for micro and mesothermal valleys camelids from Northwest Argentina
Authors: Killian Galván Violeta Anahí , Belotti López de Medina Carlos Raúl , Bugliani María Fabiana , Spano Romina Clara
Published: December 2024

Introduction

Domestic and wild camelids were the most significant meat resource for pre-Hispanic agropastoral societies in the Argentine Northwest's micro valleys (between 2,500 and 3,400 masl) and mesothermal valleys (2,500 and 1,500 masl), with varying relative importance in comparison to cultivated and collected plants. Examining pastoral movement techniques, as well as the areas available for wild resource gathering, allows us to acquire a better understanding of the nature and scale of social structure among these human communities. Stable isotope analyses of carbon (13C/12C; δ13C) and nitrogen (15N/14N; δ15N) provide efficient tools for understanding these features.

Methods

The article shows the bone collagen measurements of a sample of camelid bones from archaeofaunas recovered from Soria 2 sites (n = 7) and structure 93 of Loma l'Ántigo (n = 5), all in Catamarca province. The first is a residential unit in the Yocavil valley (2,400 masl), and its chronology corresponds to the beginning of the region's Formative Period. The second is in the Cajón Valley (2,700 masl) and dates to the Regional Developments Period. Bone specimens were previously categorized to genus or species rank employing morphological and osteometric criteria.

Results

Our results suggest that C4 plants have been important in animal diets since the Formative period. At the same time, access to pastures or wildlife at high altitudinal levels persisted during the Regional Developments, with the possibility of a fodder intensification strategy also based on C3 plants.

Discussion

Such kind of data allows us to assess whether a livestock intensification plan based on corn provision coincided with social, political, and economic changes in the early second millennium AD.
Tree-ring δ18O and δ2H stable isotopes reflect the global meteoric water line
Authors: Arosio Tito , Büntgen Ulf , Nicolussi Kurt , Moseley Gina E. , Saurer Matthias , Pichler Thomas , Smith M. Paul , Gutierrez Emilia , Andreu-Hayles Laia , Hajdas Irka , Bebchuk Tatiana , Leuenberger Markus
Published: December 2024

Introduction

The Global Meteoric Water Line (GMWL) describes the linear relationship between stable hydrogen (δ2H) and oxygen (δ18O) isotopes in precipitation over large spatial scales and therefore represents a unique reference for water isotopic values. Although trees have the potential to capture the isotopic composition of precipitation, it remains unclear if the GMWL can be reconstructed from tree-ring stable isotopes, since δ18O and δ2H undergo in vivo physiological fractionation.

Methods

We analyze the tree rings δ18O and δ2H values from six regions along a latitudinal gradient from Spain to Greenland.

Results

The data show that the covariance between δ18O and δ2H closely follows the GMWL, which reflects the isotopic signature of large-scale precipitation patterns. We show that changes in regional tree-ring δ18O and δ2H values along wide latitudinal ranges are influenced by the isotopic composition of precipitation with temperature and latitude being the most significant drivers of spatial variation across the studied regions. In contrast, local tree-ring δ18O and δ2H values are mainly controlled by plant physiological fractionation processes that mask the isotopic signature of precipitation.

Conclusion

We conclude that covariance in tree-ring δ18O and δ2H reflects the GMWL at larger spatial scales, but not when evaluating them at individual sites.
Case report: A 51-year-old diabetic patient with primary bilateral macronodular adrenal hyperplasia and primary hyperparathyroidism
Authors: Zhong Yuan , Zhang Tao , Li Fan , Chen Yong , Tong Liwei , Xia Chenxi , Wei Dong
Published: December 2024

A 51-year-old female patient with diabetes mellitus and hypertension, exhibiting poor control of blood sugar and blood pressure, was unexpectedly found to have multiple large adrenal nodules, excessive cortisol secretion, and adrenocorticotropic hormone inhibition. Cortisol levels remained unresponsive to both low-dose and high-dose dexamethasone tests, leading to a diagnosis of primary bilateral macronodular adrenal hyperplasia. Concurrently, elevated blood calcium and parathyroid hormone levels, along with 99mTc-methoxyisobutyl isonitrile (99mTc-MIBI) imaging revealing increased 99mTc-MIBI uptake in the right inferior parathyroid gland, suggest the consideration of primary hyperparathyroidism. This case is presented in light of the uncommon clinical coexistence of primary bilateral macronodular adrenal hyperplasia and primary hyperparathyroidism.
The characteristic expression of circulating MicroRNAs in osteoporosis: a systematic review and meta-analysis
Authors: Gao Jie , Zhang Xiuzhen , Ding Jing , Zhang Houli , Zhang Xu , Jiang Juan , Chen Wenwen
Published: December 2024

Objective

To evaluate the characteristics of the circulating microRNA expression profiles in patients with osteoporosis.

Methods

A systematic literature search was performed using the Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and WANFANG databases from inception until 1 March 2024. The search strategy employed keywords, encompassing “osteoporosis”, “bone loss”, or “osteopenia” and “miRNA” or “microRNA”. The Newcastle-Ottawa Scale (NOS) quality assessment scale was used to evaluate the methodological quality. Heterogeneity tests and statistical analyses of all data were performed by Stata 16.0. The differences in microRNA levels between groups were illustrated by the weighted mean difference (WMD) and 95% confidence interval (95% CI).

Results

A total of 27 studies were included and analyzed in the meta-analysis, with 2,263 participants. The results showed that miR-21-5p (WMD 0.88, 95% CI: 0.22 to 1.55), miR-125b-5p (WMD 6.63, 95% CI: 0.19 to 13.08), miR-483-5p(WMD 6.43, 95% CI: 3.26 to 9.61), miR-133a (WMD 1.43, 95% CI: 1.39 to 1.47), miR-422a (WMD 1, 95% CI: 0.28 to 1.72), and miR-214-3p (WMD 2.03, 95% CI: 0.14 to 3.92) were significantly upregulated, and miR-497-5p (WMD -0.57, 95% CI: -0.98 to -0.17) was significantly downregulated.

Conclusion

miR-21-5p, miR-125b-5p, miR-483-5p, miR-133a, miR-497-5p, miR-422a, and miR-214-3p might serve as potential diagnostic biomarkers for osteoporosis. In the future, integrating these miRNAs to build a diagnostic model might be a promising diagnosis strategy for osteoporosis.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023481209.
Localization is the key to action: regulatory peculiarities of lncRNAs
Authors: Poloni Joice de Faria , Oliveira Fábio Henrique Schuster de , Feltes Bruno César
Published: December 2024

To understand the transcriptomic profile of an individual cell in a multicellular organism, we must comprehend its surrounding environment and the cellular space where distinct molecular stimuli responses are located. Contradicting the initial perception that RNAs were nonfunctional and that only a few could act in chromatin remodeling, over the last few decades, research has revealed that they are multifaceted, versatile regulators of most cellular processes. Among the various RNAs, long non-coding RNAs (LncRNAs) regulate multiple biological processes and can even impact cell fate. In this sense, the subcellular localization of lncRNAs is the primary determinant of their functions. It affects their behavior by limiting their potential molecular partner and which process it can affect. The fine-tuned activity of lncRNAs is also tissue-specific and modulated by their cis and trans regulation. Hence, the spatial context of lncRNAs is crucial for understanding the regulatory networks by which they influence and are influenced. Therefore, predicting a lncRNA’s correct location is not just a technical challenge but a critical step in understanding the biological meaning of its activity. Hence, examining these peculiarities is crucial to researching and discussing lncRNAs. In this review, we debate the spatial regulation of lncRNAs and their tissue-specific roles and regulatory mechanisms. We also briefly highlight how bioinformatic tools can aid research in the area.
Impaired interhemispheric synchrony in patients with iridocyclitis and classification using machine learning: an fMRI study
Authors: Tong Yan , Wen Zhi , Huang Xin
Published: December 2024

Background

This study examined the interhemispheric integration function pattern in patients with iridocyclitis utilizing the voxel-mirrored homotopic connectivity (VMHC) technique. Additionally, we investigated the ability of VMHC results to distinguish patients with iridocyclitis from healthy controls (HCs), which may contribute to the development of objective biomarkers for early diagnosis and intervention in clinical set.

Methods

Twenty-six patients with iridocyclitis and twenty-six matched HCs, in terms of sex, age, and education level, underwent resting-state functional magnetic resonance imaging (fMRI) examinations. The study employed the voxel-mirrored homotopic connectivity (VMHC) technique to evaluate interhemispheric integration functional connectivity indices at a voxel-wise level. The diagnostic efficacy of VMHC was evaluated using a support vector machine (SVM) classifier, with classifier performance assessed through permutation test analysis. Furthermore, correlation analyses was conducted to investigate the associations between mean VMHC values in various brain regions and clinical features.

Results

Patients with iridocyclitis exhibited significantly reduced VMHC signal values in the bilateral inferior temporal gyrus, calcarine, middle temporal gyrus, and precuneus compared to HCs (voxel-level P < 0.01, Gaussian Random Field correction; cluster-level P < 0.05). Furthermore, the extracted resting-state zVMHC features effectively classified patients with iridocyclitis and HCs, achieving an area under the receiver operating characteristic curve (AUC) of 0.74 and an overall accuracy of 0.673 (P < 0.001, non-parametric permutation test).

Conclusion

Our findings reveal disrupted interhemispheric functional organization in patients with iridocyclitis, offering insight into the pathophysiological mechanisms associated with vision loss and cognitive dysfunction in this patient population. This study also highlights the potential of machine learning in ophthalmology and the importance of establishing objective biomarkers to address diagnostic heterogeneity.
The histamine analogue clobenpropit modulates IRF7 phosphorylation and interferon production by targeting CXCR4 in systemic lupus erythematosus models
Authors: Bekaddour Nassima , Smith Nikaïa , Caspar Birgit , Grinberg Severine , Giorgiutti Stephane , Rodeschini Vincent , Dupuy Stephanie , Leboulanger Nicolas , Duffy Darragh , Soulas-Sprauel Pauline , Gies Vincent , Korganow Anne-Sophie , Nisole Sébastien , Herbeuval Jean-Philippe
Published: December 2024

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an overactive immune response, particularly involving excessive production of type I interferons. This overproduction is driven by the phosphorylation of IRF7, a crucial factor in interferon gene activation. Current treatments for SLE are often not very effective and can have serious side effects.

Methods

Our study introduces clobenpropit, a histamine analogue, as a potential new therapy targeting the CXCR4 receptor to reduce IRF7 phosphorylation and subsequent interferon production. We employed various laboratory techniques to investigate how clobenpropit interacts with CXCR4 and its effects on immune cells from healthy individuals and SLE patients.

Results

Clobenpropit binds effectively to CXCR4, significantly inhibiting IRF7 phosphorylation and reducing interferon production. Additionally, clobenpropit lowered levels of pro-inflammatory cytokines in a mouse model of lupus, demonstrating efficacy comparable to the standard treatment, prednisolone.

Discussion

These results suggest that clobenpropit could be a promising new treatment for SLE, offering a targeted approach with potential advantages over current therapies.
C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis
Authors: Yin Junping , Verschoor Admar , Yue Xiaoyang , Goldmann Torsten , Heidecke Harald , Riemekasten Gabriela , Petersen Frank , Yu Xinhua
Published: December 2024

Introduction

Autoantibody-mediated complement activation plays an essential role in a variety of autoimmune disorders. However, the role of complement in systemic sclerosis (SSc) remains largely unknown. In this study, we aimed to determine the role of complement C3 in the development of a recently described SSc mouse model based on autoimmunity to angiotensin II receptor type 1 (AT1R).

Methods

Mice were immunized with cell membrane extract isolated from Chinese hamster ovary (CHO) cells overexpressing AT1R or non-transfected CHO cells as a control. Peripheral blood, dorsal skin and the lung were then collected to evlauate disease characteristics. Apoptotic cells in the lung of mice were detected using the DeadEnd™ Fluorometric TUNEL System.

Results

Our results showed that experimental SSc in this model was featured by the deposition of IgG, but not of complement C3, in the lung. After immunization with AT1R, C3-deficient mice developed more severe pulmonary inflammations than wild type controls, whereas skin inflammation and fibrosis were not different as well as the anti-AT1R ab levels. Further, C3-deficient mice showed an increased rate of pulmonary cell apoptosis as compared to controls. The apoptosis rate correlated with the corresponding degree of lung inflammation.

Discussion

Taken together, our findings suggest an anti-apoptotic and anti-inflammatory role of complement C3 in pulmonary autoimmune inflammation.
Single-cell transcriptomics reveals heterogeneity and prognostic markers of myeloid precursor cells in acute myeloid leukemia
Authors: He Guangfeng , Jiang Lai , Zhou Xuancheng , Gu Yuheng , Tang Jingyi , Zhang Qiang , Hu Qingwen , Huang Gang , Zhuang Ziye , Gao Xinrui , Xu Ke , Xiao Yewei
Published: December 2024

Background

Acute myeloid leukemia (AML) is a hematologic tumor with poor prognosis and significant clinical heterogeneity. By integrating transcriptomic data, single-cell RNA sequencing data and independently collected RNA sequencing data this study aims to identify key genes in AML and establish a prognostic assessment model to improve the accuracy of prognostic prediction.

Materials and methods

We analyzed RNA-seq data from AML patients and combined it with single-cell RNA sequencing data to identify genes associated with AML prognosis. Key genes were screened by bioinformatics methods, and a prognostic assessment model was established based on these genes to validate their accuracy.

Results

The study identified eight key genes significantly associated with AML prognosis: SPATS2L, SPINK2, AREG, CLEC11A, HGF, IRF8, ARHGAP5, and CD34. The prognostic model constructed on the basis of these genes effectively differentiated between high-risk and low-risk patients and revealed differences in immune function and metabolic pathways of AML cells.

Conclusion

This study provides a new approach to AML prognostic assessment and reveals the role of key genes in AML. These genes may become new biomarkers and therapeutic targets that can help improve prognostic prediction and personalized treatment of AML.
Regulation of epidermal barrier function and pathogenesis of psoriasis by serine protease inhibitors
Authors: Wang Juanjuan , Li Junqin , Zhou Ling , Hou Hui , Zhang Kaiming
Published: December 2024

Serine protease inhibitors (Serpins) are a protein superfamily of protease inhibitors that are thought to play a role in the regulation of inflammation, immunity, tumorigenesis, coagulation, blood pressure and cancer metastasis. Serpins is enriched in the skin and play a vital role in modulating the epidermal barrier and maintaining skin homeostasis. Psoriasis is a chronic inflammatory immune-mediated skin disease. At present, most serpins focus on the pathogenesis of psoriasis vulgaris. Only a small number, such as the mutation of SerpinA1/A3/B3, are involved in the pathogenesis of GPP. SerpinA12 and SerpinG1 are significantly elevated in the serum of patients with psoriatic arthritis, but their specific mechanism of action in psoriatic arthritis has not been reported. Some Serpins, including SerpinA12, SerpinB2/B3/B7, play multiple roles in skin barrier function and pathogenesis of psoriasis. The decrease in the expression of SerpinA12, SerpinB7 deficiency and increase in expression of SerpinB3/4 in the skin can promote inflammation and poor differentiation of keratinocyte, with damaged skin barrier. Pso p27, derived from SerpinB3/B4, is an autoantigen that can enhance immune response in psoriasis. SerpinB2 plays a role in maintaining epidermal barrier integrity and inhibiting keratinocyte proliferation. Here we briefly introduce the structure, functional characteristics, expression and distribution of serpins in skin and focus on the regulation of serpins in the epidermal barrier function and the pathogenic role of serpins in psoriasis.
Case report: Detecting giant cell arteritis in [68Ga]Ga-DOTA-Siglec-9-PET/CT
Authors: Petzinna Simon M. , Küppers Jim , Schemmer Benedikt , Kernder Anna L. , Bauer Claus-Jürgen , von der Emde Leon , Salam Babak , Distler Jörg H. W. , Winklbauer Anja , Essler Markus , Schäfer Valentin S.
Published: December 2024

Objectives

This study aimed to evaluate the diagnostic utility of [68Ga]Ga-DOTA-Siglec-9 positron emission tomography-computed tomography (PET/CT) in assessing disease activity in a patient experiencing a relapse of giant cell arteritis (GCA).

Case presentation

A 90-year-old male patient with GCA, diagnosed in 2018, was enrolled. Demographic data, disease history, and laboratory parameters, including soluble VAP-1 (sVAP-1) levels, were recorded. The patient underwent a [68Ga]Ga-DOTA-Siglec-9 PET/CT scan. Additional imaging assessments included vascular ultrasound of the superficial temporal arteries, their branches, and the facial, axillary, subclavian, carotid, and vertebral arteries, along with magnetic resonance imaging (MRI) of the aorta.

The patient’s sVAP-1 level was 284 ng/ml compared to 123 ng/ml in the control group (SD ± 55). The [68Ga]Ga-DOTA-Siglec-9 PET/CT scan revealed increased tracer uptake (SUVmax) in the subclavian artery (2.5), aortic arch (2.9), and heart (2.9). Notably, the increased uptake in the descending aorta (3.5) abruptly diminished to 2.2 when passing the diaphragm, with no changes in vessel caliber observed in CT. The injection of [68Ga]Ga-DOTA-Siglec-9 was well tolerated. Aortic MRI revealed no signs of inflammatory involvement.

Conclusions

This study introduces the first application of [68Ga]Ga-DOTA-Siglec-9 PET/CT in a patient with GCA experiencing a relapse, revealing enhanced tracer uptake in the subclavian artery and aortic arch with a localized and abrupt reduction, absent in conventional imaging. These findings suggest that [68Ga]Ga-DOTA-Siglec-9 PET/CT has significant potential for precise, inflammation-specific detection of affected vascular tissue in GCA during relapse.
Enhancement of body red coloration in juvenile spotted scat (Scatophagus argus) by dietary supplementation with Lianjiang red orange peels as a natural carotenoid source
Authors: Han Tong , Liao Yongguan , Yang Lei , Li Xinyi , Shi Gang , Jiang Dong-Neng , Zhu Chunhua , Li Guangli , Shi Hongjuan
Published: December 2024

Spotted scat (Scatophagus argus) is an economically important marine species in China, with high ornamental and edible value. The effects of dietary supplementation of Lianjiang red orange peels, a natural carotenoid source, at 0, 3, 6, 9 and 12%, hereafter referred to as G0, G3, G6, G9 and G12, were measured on color values, carotenoid content, expression of genes such as cyp2j6, cyp1a1, hsp70, slc2a11, bco2, cyp26c1 after 4 weeks. Subsequently, the different color values (L*, a*, and b*), total carotenoids content, and gene expression pattern were analyzed. In the groups fed diets containing more than 9% Lianjiang red orange peels (9% and 12%), the L* value (lightness) decreased, while the a* value (redness) increased in red skin, and b* value (yellowness) increased in caudal fin (P < 0.05). Additionally, the total carotenoids content in red skin of the G9 group and caudal fin of the G12 group was substantially higher than in the other groups (P < 0.05). By comparative transcriptome analysis of the red skin in G0 and G9 groups, 419 differentially expressed genes (DEGs) were identified, of which 237 were upregulated and 182 were downregulated. Genes involved in carotenoid deposition (cyp2j6, cyp1a1) and pigment cell development (hsp70, slc2a11) were significantly upregulated, whereas genes related to carotenoid decomposition (bco2) and retinoic acid metabolism (cyp26c1) were significantly downregulated in the G9 group. These findings suggest that Lianjiang red orange peels, as a natural carotenoid source, enhance body coloration by influencing the deposition of carotenoid, pteridine pigments, erythrophore development, and inhibiting the oxidative cleavage of carotenoid and retinoic acid metabolism. This study enhances body coloration by influencing carotenoid and pteridine pigment deposition, and provides theoretical guidance for aquaculture practices involving spotted scat.
Alpha-1 antitripsyn deficiency and augmentation therapy in pregnancy: two case reports
Authors: Annunziata Anna , Fiorentino Giuseppe , Coppola Antonietta , Cauteruccio Rosa , Ferrentino Laura , Fiorentino Luigi , Calabrese Cecilia
Published: December 2024

Alpha-1 antitrypsin deficiency (AATD) is an inherited condition characterized by reduced plasma levels of alpha-1 antitrypsin (AAT), often leading to pulmonary diseases primarily emphysema and/or chronic obstructive pulmonary disease (COPD), but also bronchiectasis, bronchial asthma, or other less common disorders. Early diagnosis enables AAT augmentation therapy, which has proven to be effective in slowing down functional decline and improving survival rates. This article presents two cases of pregnant women with rare allelic variants of AATD who received AAT augmentation therapy, exploring the limited evidence on its safety during pregnancy and the potential role of decreased serum AAT levels in pregnancy-related complications.
Altered brain glymphatic function on diffusion-tensor MRI in patients with spontaneous intracerebral hemorrhage: an exploratory study
Authors: Xia Xiaona , Ren Qingguo , Zhang Juntao , Guan Shuai , Jiang Qingjun , Wei Ying , Hua Rui , Zhao Shen , Hu Xiangjun , Shi Feng , Meng Xiangshui
Published: December 2024

Objectives

To investigate the function of the glymphatic system (GS) and its association with neuropsychological tests in spontaneous intracerebral hemorrhage (sICH) by diffusion tensor imaging analysis along the perivascular space (DTI-ALPS).

Methods

This retrospective study included 58 patients with sICH and 63 age- and sex-matched healthy controls (HCs). Partial correlation analyses were performed to examine the relationships between the DTI-ALPS index and radiological as well as clinical data. Mediation analyses were performed to explore the mediating role of the grey matter proportion (GM%) in the relationship between DTI-ALPS index and Montreal Cognitive Assessment (MoCA) score.

Results

Significantly lower DTI-ALPS index values were observed in sICH compared with HCs (FDR-p < 0.001). In the acute-subacute sICH group, the ALPS index was significantly correlated with hematoma volume (r = −0.572, FDR-p = 0.031). In the chronic sICH group, the ALPS index was significantly correlated with MoCA scores (r = 0.425, FDR-p = 0.014). In chronic sICH groups, GM% served as a significant mediator in the relationship between the DTI-ALPS index and MoCA scores (indirect effects β = 4.925, 95%CI: 0.028, 11.841). The ALPS index was identified as an independent prognostic indicator for unfavorable outcomes in sICH (β = −9.851, p = 0.018).

Conclusion

Our study demonstrated that the DTI-ALPS index decreased in sICH patients, suggesting potential functional impairment of the lymphoid system. Additionally, the DTI-ALPS index served as an independent predictor of poor 90-day prognosis. In the acute-subacute stage of sICH, the DTI-ALPS index had negative correlation with hematoma volume. In the chronic sICH group, the GM% partially mediated the relationship between the GS and cognitive function.
Heterogeneous appetite patterns in depression: computational modeling of nutritional interoception, reward processing, and decision-making
Authors: Uchida Yuuki , Hikida Takatoshi , Honda Manabu , Yamashita Yuichi
Published: December 2024

Accurate interoceptive processing in decision-making is essential to maintain homeostasis and overall health. Disruptions in this process have been associated with various psychiatric conditions, including depression. Recent studies have focused on nutrient homeostatic dysregulation in depression for effective subtype classification and treatment. Neurophysiological studies have associated changes in appetite in depression with altered activation of the mesolimbic dopamine system and interoceptive regions, such as the insular cortex, suggesting that disruptions in reward processing and interoception drive changes in nutrient homeostasis and appetite. This study aimed to explore the potential of computational psychiatry in addressing these issues. Using a homeostatic reinforcement learning model formalizing the link between internal states and behavioral control, we investigated the mechanisms by which altered interoception affects homeostatic behavior and reward system activity via simulation experiments. Simulations of altered interoception demonstrated behaviors similar to those of depression subtypes, such as appetite dysregulation. Specifically, reduced interoception led to decreased reward system activity and increased punishment, mirroring the neuroimaging study findings of decreased appetite in depression. Conversely, increased interoception was associated with heightened reward activity and impaired goal-directed behavior, reflecting an increased appetite. Furthermore, effects of interoception manipulation were compared with traditional reinforcement learning parameters (e.g., inverse temperature β and delay discount γ), which represent cognitive-behavioral features of depression. The results suggest that disruptions in these parameters contribute to depressive symptoms by affecting the underlying homeostatic regulation. Overall, this study findings emphasize the importance of integrating interoception and homeostasis into decision-making frameworks to enhance subtype classification and facilitate the development of effective therapeutic strategies.