bluuebunny/crossref_metadata_2025 huggingface dataset:
Kopioita, korvikkeita ja aidon veroisia?
Authors: Haittoniemi Mia
Published: December 2024

Synteettiset jalokivet ovat ihmisen valmistamia mineraaleja, jotka vastaavat ominaisuuksiltaan lähes täydellisesti luonnossa syntyneitä esikuviaan. Niiden kaupallinen tuotanto jalokivialaa varten alkoi 1900-luvun alussa. Vuosisadan edetessä synteettiset kivet muodostivat jatkuvasti kehittyvän tuoteryhmän, jonka vaiheita jalokivien parissa toimivien täytyi seurata aktiivisesti. Lähilukemalla kultasepänalan ammattioppaita ja jalokivikirjoja artikkeli tutkii, mitä suomalaiset jalokiviasiantuntijat kirjoittivat synteettisistä jalokivistä vuosina 1900–1969. Miten he suhtautuivat jalokiven synteettisyyteen, synteettisten jalokivien kaupalliseen merkitykseen ja mahdollisuuksiin erottaa ihmisen valmistamat jalokivet luonnossa syntyneistä? Miten suhtautuminen muuttui ajan kuluessa?
Tutkimusjakson alussa synteettisiin jalokiviin liittyvä jalokiviasiantuntijuus nojasi silmämääräisiin havaintoihin ja kokemukseen. Niiden merkitys alkoi kuitenkin vähitellen väistyä ja 1960-luvulle tultaessa gemmologisten tutkimuslaitteiden tuottamat, varmoina pidetyt, tutkimustulokset saivat yhä enemmän painoarvoa. Asiantuntijoiden mukaan synteettisillä jalokivillä oli oma paikkansa jalokivikaupassa ja niiden kaupallinen merkitys oli suuri. Tarve tunnistaa synteettisyys ja erotella synteettiset jalokivet aidoista vauhditti uuden toimijaryhmän – gemmologien – muodostumista Suomessa. Samalla gemmologiasta kehittyi erityisala, joka ei enää täysin auennut muille jalokivien parissa toimiville.
Sistem Pendukung Keputusan dalam Menentukan Penerima Program Indonesia Pintar (PIP) Menggunakan Metode SAW pada SMA Negeri 6 Padang
Authors: Puspita Retchi , Selvanda Alifia Restu
Published: December 2024

Pendidikan merupakan kebutuhan dasar yang harus dipenuhi oleh seluruh masyarakat Indonesia karena berfungsi sebagai sarana utama untuk mencerdaskan kehidupan bangsa. Di Indonesia, pemerintah telah menerapkan program wajib belajar selama 6 tahun yang mencakup pendidikan di tingkat sekolah dasar, sekolah menengah pertama, dan sekolah menengah atas. Saat ini, pemerintah telah menghadirkan inovasi baru di bidang pendidikan untuk meningkatkan kesejahteraan masyarakat melalui bantuan berupa Program Indonesia Pintar (PIP) yang disalurkan melalui Kartu Indonesia Pintar (KIP). Sistem Pendukung Keputusan (SPK) adalah sistem berbasis komputer yang dirancang untuk membantu proses pengambilan keputusan dengan menggunakan data dan model tertentu guna menyelesaikan masalah yang bersifat semi-terstruktur. SPK diterapkan dalam berbagai bidang, salah satunya adalah bidang perkantoran, misalnya untuk menentukan karyawan terbaik. Penelitian ini bertujuan untuk merancang sistem yang dapat memberikan rekomendasi terbaik dalam menentukan penerima Program Indonesia Pintar (PIP) di SMA N 6 Padang. Metode yang digunakan adalah metode Simple Additive Weighting (SAW). Dengan adanya sistem pendukung keputusan berbasis web, diharapkan SMA N 6 Padang dapat terbantu dalam proses seleksi penerima Program Indonesia Pintar (PIP). Berdasarkan pengujian, metode ini menghasilkan tingkat akurasi lebih dari 90% berdasarkan data yang diolah. Melalui hasil evaluasi menggunakan metode SAW, penelitian ini berhasil menentukan penerima Program Indonesia Pintar di SMA N 6 Padang berdasarkan nilai tertinggi yang diperoleh.
Detection and Identification of Wheat Pest Chaetopteroplia segetum (Coleoptera: Scarabaeidae)
Authors: Beram Refika Ceyda , Tashıgul Nurzhan , Bayındır Erol Alime
Published: December 2024

Anisopliines are an important group of insects associated with both cultivated plants and wild weeds. Chaetopteroplia segetum (Herbst, 1783) (Coleoptera: Scarabaeidae), although preferring natural plants, can cause significant damage to agricultural crops such as wheat, rye, and corn, posing a major threat to agricultural fields. This species is widely distributed across Europe and Asia, and C. segetum has been reported in several provinces in Türkiye. However, despite its extensive geographical range, the phylogenetic relationships within the Scarabaeidae family remain poorly understood. This study aimed to detect, identify, and investigate the phylogenetic relationships of this wheat pest across various agricultural fields in the Çivril district of Denizli province, Türkiye. The surveys were systematically conducted between June and July 2023, with monthly sample collections carried out at predetermined locations within twelve different fields. The collected samples were morphologically characterized, and the morphological identification was further confirmed through molecular analysis of representative samples from each field. After DNA isolation, a partial fragment of the cytochrome oxidase I (COI) gene was amplified using universal barcode primers LCO1490F and HCO2198R. BLAST analysis revealed that all collected individuals exhibited 99%–100% similarity with previously reported C. segetum sequences. Furthermore, a phylogenetic tree was constructed using the neighbor-joining method with MEGA X software, based on COI gene region data, to elucidate the relationships among the individuals. Currently, there is limited information on the molecular classification of the Scarabaeidae family in Türkiye. The findings of this study contribute to bridging this gap by providing a foundation for future molecular research aimed at better understanding the genetic structure and phylogenetic relationships within this family.
Perancangan Peta Wisata Interaktif Kota Cilegon Sebagai Panduan Komprehensif Bagi Wisatawan
Authors: Wildan Rian Agni , Gumelar Rangga Galura
Published: December 2024

Penelitian ini mengembangkan Peta Wisata Interaktif Kota Cilegon sebagai panduan komprehensif bagi wisatawan. Tujuan dari penelitian ini adalah untuk memudahkan wisatawan dalam mencari informasi mengenai objek wisata, akomodasi, dan fasilitas umum di Kota Cilegon. Proses pengembangan melibatkan penggunaan software Ibis Paint X dan Canva untuk desain peta. Data dikumpulkan dari sumber terpercaya seperti situs web resmi, brosur wisata, dan wawancara dengan penduduk lokal. Hasilnya adalah pamflet digital dalam format PDF yang interaktif dan informatif. Peta ini dirancang untuk dapat diakses secara digital maupun cetak, memberikan fleksibilitas bagi pengguna.
MAUPASSANT’IN L’INUTILE BEAUTÉ BAŞLIKLI ÖYKÜSÜNÜN ÇEVİRİLERİNİN ANLAM EVRİLMESİ EĞİLİMLERİ AÇISINDAN DEĞERLENDİRİLMESİ
Authors: Şen Dağtekin Gülseren
Published: December 2024

Fransız ve dünya edebiyatının önde gelen isimlerinden öykü ve roman yazarı Guy de Maupassant’ın L’Inutile Beauté başlıklı öyküsü, yazarın eserleri arasında önemli bir yere sahiptir. Bu çalışmada incelediğimiz çeviriler, eserin 1924 yılında yayınlanan İngilizce çevirisi ile Türkiye’de 2000 ve 2023 yıllarında yayınlanan Türkçe çevirileridir. Bu çalışmada hedeflenen, “Öykünün üzerine kurulu olduğu bir gizem söz konusu olduğu için özellikle bu gizeme ilişkin kısımlar ile ilgili çevirmenlerin tercihleri okurun okuma etkinliğini nasıl etkilemektedir?” sorusuna cevap aramaktır. Çevirilerin değerlendirmesine başlamadan önce yazar ve öykü tanıtılmış, öykü ayrıntılı bir şekilde özetlenmiştir. Daha sonra, metnin çeviri açısından en önemli unsurları göstergebilimsel çözümleme ile ele alınmıştır. Bu çözümleme, metnin kesitlenmesi, öykünün sorunsalı ve metnin başlığı, birincil söyleyen ve tasarlanmış sözceleyenler, bakış açıları ve öyküdeki bilmece, öykü zamanı ve söylem zamanı, anlatı izlenceleri, eyleyenlerin donanımları, söyleyenlerin öznelik dönüşümleri, hakikate uygunluk ve metinde oluşan yerdeşlikler ile ilgili incelemeler aracılığıyla yapılmıştır. Çevirileri incelemek için Sündüz Öztürk Kasar’ın geliştirdiği “Anlam Evrilmesi Dizgeselliği”nden yararlanılmıştır. Çevirilerin değerlendirilmesi, çeviri metinlerde tespit edilen anlam evrilmesi eğilimleri (otuz örnek) hakkında yorumlardan ve gözlemlerden oluşmaktadır. En çok anlam evrilmesi eğilimi gösteren metin, on sekiz örnek ile “Sorun Yaratan Güzellik” başlıklı çeviridir. “Beyhude Güzellik” başlıklı çeviride ise on örnek bulunurken, Useless Beauty başlıklı çeviride yalnızca iki örnek tespit edilmiştir. Bu alanda yapılan birçok çalışmanın da gösterdiği gibi, göstergebilim ve çeviri göstergebilimi, yazınsal çeviri yapanların, edebi eserlerin bir dilden başka bir dile anlam yolculuğunu gerçekleştirmesinde başvurabileceği bir kılavuz niteliğindedir. Bu çalışma, çevirilerdeki anlam evrilmelerinden kaynaklanan müdahalelerin, Maupassant’ın öykülerinin çevirileri aracılığıyla okuyanların anlamlandırma sürecini de etkileyebileceğini göstermektedir.
Current Techniques and Engineering Opportunities for Advancement and Improvement in Electroencephalographic Acquisition and Analyses
Authors: Swaminathan Arun
Published: December 2024

Epilepsy is a highly prevalent condition and affects about 50-65 million people worldwide with great impact on health and quality of life, including medical and social aspects. Electroencephalography (EEG) represents the main diagnostic approach to evaluate patients with epilepsy. EEG techniques have achieved significant improvement over the years and keep evolving to meet increasing demands such as higher accuracy, innovation and better quality and technique to enable improved diagnosis and treatment of epilepsy and other conditions. We use this paper to discuss current techniques and future opportunities for advancement of different types of EEG and various aspects of its use, along with avenues for improving EEG related engineering and technology. We wish to enumerate various aspects of EEG hardware and capturing techniques to discuss opportunities for improvement, along with detailing the utility of software advances including quantitative EEG and EEG analyses. We also aim to discuss neurostimulation and its role in advancing the management of epilepsy. Finally, we also discuss the use of EEG in non-epilepsy conditions. We aim to showcase current capabilities and expand on these to describe opportunities for advancement in diagnosis and management using EEG for a variety of indications. Our paper seeks to detail various aspects of EEG advancement that can improve overall patient care and research.
TWO NEW LAWS OF GRAVITATION GIVE A COMPLETE DESCRIPTION OF GRAVITATIONAL INTERACTION IN THE UNIVERSE
Authors: Kosinov Mykola
Published: December 2024

For more than 300 years, the formula for the force of gravitational interaction is represented by Newton's Uniform Law of Universal Gravitation. During this period the facts that Newton's law of gravitation gives predictions that do not agree with observations have been revealed. Here we show that Newton's law of gravitation is not the only law of gravitational interaction in the universe. In addition to Newton's law of gravitation, a new law of gravitation is obtained: FCos=(mc^2)√Ʌ. The two laws of gravitation (FN=GmM/r^2, FCos=(mc^2)√Ʌ) revitalize classical gravity and develop Newtonian dynamics towards a complete model of gravity. Newton's law of gravitation together with the new law of gravitation provide a complete and consistent description of the gravitational interaction in the universe. The real law of universal gravitation is presented in a new form. The law of universal gravitation is represented by two equivalent formulas: FU=GmM/r^2+(mc^2)√Ʌ; FU=mR^3/T^2*r^2+(mc^2)√Ʌ. The law of universal gravitation turned out to be much more complicated than Newton claimed.
Hur presenteras olika sexualiteter och kroppar i biologiböcker och klassrumsundervisning?
Authors: Junkala Hannele
Published: December 2024

Skolan har en viktig roll för lärande om sexuell mångfald och hur normer kan begränsa identitet och relationer. Samtidigt är det den plats där unga hbtq-personer är mest utsatta för kränkningar. Ämnesområdet ”Sexualitet, samtycke och relationer” ska enligt läroplanen integreras i de flesta av skolans ämnen. Det kan dock vara utmanande för lärare att ge elever en vidgad och aktuell undervisning inom området. Syftet med den här artikeln är att presentera verktyg som lärare kan inspireras av, baserat på resultat från min avhandling om hur olika sexualiteter och kroppar konstrueras i sexualundervisning inom biologiämnet på högstadiet.
Anticarcinogenic effects of ursodeoxycholic acid in pancreatic adenocarcinoma cell models
Authors: Kovács Patrik , Schwarcz Szandra , Nyerges Petra , Bíró Tímea Ingrid , Ujlaki Gyula , Bai Péter , Mikó Edit
Published: December 2024

Changes to the composition of the microbiome in neoplasia, is termed oncobiosis, may affect tumor behavior through the changes to the secretion of bacterial metabolites. In this study we show, that ursodeoxycholic acid (UDCA), a bacterial metabolite, has cytostatic properties in pancreatic adenocarcinoma cell (PDAC) models. UDCA in concentrations corresponding to the human serum reference range suppressed PDAC cell proliferation. UDCA inhibited the expression of epithelial mesenchymal transition (EMT)-related markers and invasion capacity of PDAC cells. UDCA treatment increased oxidative/nitrosative stress by reducing the expression of nuclear factor, erythroid 2-like 2 (NRF2), inducing inducible nitric oxide synthase (iNOS) and nitrotyrosine levels and enhancing lipid peroxidation. Furthermore, UDCA reduced the expression of cancer stem cell markers and the proportion of cancer stem cells. Suppression of oxidative stress by antioxidants, blunted the UDCA-induced reduction in cancer stemness. Finally, we showed that UDCA induced mitochondrial oxidative metabolism. UDCA did not modulate the effectiveness of chemotherapy agents used in the chemotherapy treatment of pancreatic adenocarcinoma. The antineoplastic effects of UDCA, observed here, may contribute to the induction of cytostasis in PDAC cell models by providing a more oxidative/nitrosative environment.
Multi-omics in exploring the pathophysiology of diabetic retinopathy
Authors: Li Xinlu , Dong XiaoJing , Zhang Wen , Shi Zhizhou , Liu Zhongjian , Sa Yalian , Li Li , Ni Ninghua , Mei Yan
Published: December 2024

Diabetic retinopathy (DR) is a leading global cause of vision impairment, with its prevalence increasing alongside the rising rates of diabetes mellitus (DM). Despite the retina’s complex structure, the underlying pathology of DR remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) and recent advancements in multi-omics analyses have revolutionized molecular profiling, enabling high-throughput analysis and comprehensive characterization of complex biological systems. This review highlights the significant contributions of scRNA-seq, in conjunction with other multi-omics technologies, to DR research. Integrated scRNA-seq and transcriptomic analyses have revealed novel insights into DR pathogenesis, including alternative transcription start site events, fluctuations in cell populations, altered gene expression profiles, and critical signaling pathways within retinal cells. Furthermore, by integrating scRNA-seq with genetic association studies and multi-omics analyses, researchers have identified novel biomarkers, susceptibility genes, and potential therapeutic targets for DR, emphasizing the importance of specific retinal cell types in disease progression. The integration of scRNA-seq with metabolomics has also been instrumental in identifying specific metabolites and dysregulated pathways associated with DR. It is highly conceivable that the continued synergy between scRNA-seq and other multi-omics approaches will accelerate the discovery of underlying mechanisms and the development of novel therapeutic interventions for DR.
Comprehensive plasma metabolomics analysis of berberine treatment in ulcerative colitis rats by LC-MS/MS
Authors: Feng Baodong , Su Linqi , Yang Yang , Liu Renyan , Zhang Yu , Xin Lingyi , Wang Li , Yang Zhiming , Wei Xuemei , Chen Qinhua
Published: December 2024

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) influenced by multiple factors. Berberine, an isoquinoline alkaloid derived from the root and bark of Coptis chinensis Franch., has shown promise in managing UC, but its underlying mechanisms remain unclear.

Methods

To elucidate the relationship between berberine, ulcerative colitis (UC), and the organism’s metabolome, we established a dextran sulfate sodium (DSS)-induced UC model in rats. Colonic tissue was collected for histopathological examination, while plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with dynamic Multiple Reaction Monitoring (dMRM). This approach, characterized by its short analysis time of 20 min per sample, excellent reproducibility, and straightforward data processing, allowed for the comprehensive detection of a wide array of metabolites, including amino acids, lipids, and organic acids, many of which are implicated in the pathophysiology of UC.

Results

Our results showed that berberine modulated the metabolic disturbances of 33 compounds in the plasma of UC rats, primarily including amino acids, pyrimidines, organic phosphoric acids, fatty acyls, and organonitrogen compounds. These altered metabolites were associated with various pathways, such as amino acid metabolism, glutathione metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, pyrimidine metabolism, glyoxylate and dicarboxylate metabolism, and the citrate cycle (TCA cycle). Notably, 3-hydroxyproline, homocysteic acid, L-threonine, L-lysine, carbamoyl phosphate, O-phosphoethanolamine, taurine, leucine, and phosphorylcholine exhibited significant differences between the Treatment and Model groups, with levels reverting to those of the Control group (p < 0.001). These findings suggested that these compounds may serve as potential plasma biomarkers for UC.

Conclusion

This study provided valuable insights into the mechanism by which berberine exerted its therapeutic effects on UC through metabolomics. Our results highlighted berberine’s potential to modulate key metabolic pathways and restore the levels of several metabolites, suggesting its utility as a therapeutic agent for UC. These findings underscored the importance of metabolomics in understanding the pathophysiology and treatment of UC.
Application of a localized morphometrics approach to imaging-derived brain phenotypes for genotype-phenotype associations in pediatric mental health and neurodevelopmental disorders
Authors: Dagasso Gabrielle , Wilms Matthias , MacEachern Sarah J. , Forkert Nils D.
Published: December 2024

Introduction

Quantitative global or regional brain imaging measurements, known as imaging-specific or -derived phenotypes (IDPs), are commonly used in genotype-phenotype association studies to explore the genomic architecture of the brain and how it may be affected by neurological diseases (e.g., Alzheimer's disease), mental health (e.g., depression), and neurodevelopmental disorders (e.g., attention-deficit hyperactivity disorder [ADHD]). For this purpose, medical images have been used as IDPs using a voxel-wise or global approach via principal component analysis. However, these methods have limitations related to multiple testing or the inability to isolate high variation regions, respectively.

Methods

To address these limitations, this study investigates a localized, principal component analysis-like approach for dimensionality reduction of cross-sectional T1-weighted MRI datasets utilizing diffeomorphic morphometry. This approach can reduce the dimensionality of images while preserving spatial information and enables the inclusion of spatial locality in the analysis. In doing so, this method can be used to explore morphometric brain changes across specific components and spatial scales of interest and to identify associations with genome regions in a multivariate genome-wide association study. For a first clinical feasibility study, this method was applied to data from the Adolescent Brain Cognitive Development (ABCD) study, including adolescents with ADHD (n = 1,359), obsessive-compulsive disorder (n = 1,752), and depression (n = 1,766).

Results

Meaningful associations of specific morphometric features with genome regions were identified with the data and corresponded to previous found brain regions in the respective mental health and neurodevelopmental disorder cohorts.

Discussion

In summary, the localized, principal component analysis-like approach can reduce the dimensionality of medical images while still being able to identify meaningful local brain region alterations that are associated with genomic markers across multiple scales. The proposed method can be applied to various image types and can be easily integrated in many genotype-phenotype association study setups.
Characteristics of strong earthquake preparation in main-seismic type and multi-seismic type earthquake segments in the North China tectonic region
Authors: Zhu Hongbin , Hu Leyin , Chen Yuxuan , Li Hong
Published: December 2024

The North China Tectonic Zone (NCTZ) is the most seismically active area in eastern China, where a large number of strong earthquakes, especially M8 or so, had occurred. In order to study the risk of future strong earthquakes in the NCTZ, we study tectonic features of strong earthquakes and the time series features of Ms ≥ 5 earthquakes since the year 1484 (MT). The results show that the 14 seismic segments of faults are classified into Main-seismic types and multi-seismic types. The characteristics of the main seismic segment include: NNE dextral strike-slip faults, only one prominent around M8 main shock has occurred since the year 1484, most of the deep and large faults cutting the Moho surface below the main earthquakes with high angles, the flower structures of tectonics. The characteristics of multi-seismic type include: NWW left-lateral strike-slip faults, NEE oriented tensional faults, convergence areas of several sets of faults since the year 1484, and the magnitude of most of them was not greater than M7.0. Finally, we analyze the strong-earthquake-generating characteristics of the similar seismic segments and discuss their strong-earthquake-generating patterns based on the relationship between the rupture zone and the main compressive stress field.
Investigation into vibration propagation and attenuation characteristics of shield construction based on field measurement
Authors: Liang Xu , Xu Jian , Zhang Yapeng , Zhou Xuetao , Xie Kuangqin , Yuan Zonghao , Zhang Min , Wu Jian , Liu Long
Published: December 2024

Vibration caused by shield tunneling construction have adverse impacts on surrounding environment. To ascertain the influence of shield tunneling construction on ambient vibration, based on the shield tunnel project of Zhijiang Road in Hangzhou, the on-site vibration tests were carried out on the deep soil and surface during the excavation, and the vibration characteristics and vibration attenuation law during shield construction were investigated. The results show that the main frequency of vibration near the vibration source is wide, and the response components can be observed at 0–100 Hz. Under the filtering effect of the surface-covering soil layer, the high-frequency components of the vibration response are significantly attenuated, and the surface vibration is mainly distributed within 40 Hz. In the shield crossing, the deep measurement point is 5 dB higher than the vibration level of the same position on the surface. After the shield is pushed forward 20 m, the average attenuation of the surface vibration response is 10 dB, and the average attenuation of the deep vibration response is 12 dB.
The impacts of international exchange programs on Moroccan teachers’ professional development: the case of in- presence programs
Authors: Oubit Sidi Mohamed , El Farahi Abdellatif
Published: December 2024

During the last decades, many Moroccan TEFL teachers have participated in different international exchange programs. Although much attention has been paid to such programs globally, there is no study that assesses the impact nationally. The actual study aims to explore the benefits of such programs on Moroccan TEFL teachers’ personal and professional development. It surveys their attitudes, knowledge and practices after they participate. This includes language awareness, techniques and strategies in teaching, leadership, soft skills and cultural competence. The results of the study prove that exchange programs promote the development of teachers’ personal, professional and intercultural competencies, namely language acquisition, intercultural understanding, easy integration in unfamiliar contexts, and efficiency in teaching. Thereafter, it in the end gives some recommendations to different partners in the educative sector in order to encourage this type of programs.
The embryo stage at fresh ET does not affect the cumulative live birth rate in women with a thin endometrium: a retrospective matched-controlled cohort study
Authors: Han Qiao-Song , Chen Yan-Hua , Zhang Bin , Song Jing-Yan , Xu Ying , Li Heng-Bing , Guo Zi-Zhen , Sun Zhen-Gao
Published: December 2024

Background

The blastocyst-stage embryo has been considered more advantageous for increasing the cumulative live birth rate (CLBR) at fresh embryo transfer (ET) compared to the cleavage-stage embryo. However, it remains uncertain whether this advantage extends to specialized subpopulations, such as women with thin endometrium (TE), who are characteristic of impaired endometrial receptivity. Thus, this study aims to evaluate the difference in the CLBR between cleavage-stage and blastocyst-stage embryos at fresh ET specifically in women with TE.

Methods

A retrospective cohort comprising 1089 women from three centers, ranging from September 2017 to January 2022, was established. These women were diagnosed with TE (defined as endometrium thickness <= 8 mm) and underwent their first fresh ET. To create a comparable cohort between the cleavage and blastocyst groups while adjusting for key covariates, the propensity score matching (PSM) method was employed. The primary outcome assessed was the CLBR per woman. Both cohorts underwent Kaplan-Meier analysis, Cox proportional hazard models, cumulative incidence function (CIF) curve analysis, and Fine-Grey competing risk models to ascertain the impact of embryo stage at fresh ET on CLBR. Additionally, a sensitivity analysis was conducted within a subgroup defining thin endometrium as an endometrium thickness (EMT) < 7 mm.

Results

In the matched cohort after PSM, the CLBR was comparable between groups (p=0.331). However, the cleavage-stage fresh ET was associated with an elevated risk of low birth weight (LBW) (p=0.005) and small for gestational age (SGA) (p=0.037). Kaplan-Meier analysis showed that the median number of embryo transfer cycles was 2 in the cleavage group and 3 in the blastocyst group. The CLBR for the cleavage group reached 78.1%, while the blastocyst group reached 60.0% after 5 cycles of embryo transfers (log-rank test, p=0.09). A multivariable Cox proportional hazard model indicated no significant association between the embryo stage at fresh ET and CLBR (HR=0.80, 95% CI=0.60-1.07). The CIF curve and Fine-Grey competing risk models demonstrated similar results. These analyses were repeated in the original cohort before PSM and in the subgroup with EMT < 7 mm, and the results remained robust.

Conclusion

For TE women receiving fresh ET, the choice between the cleavage-stage embryo and the blastocyst-stage embryo yields comparable CLBR. However, selecting the cleavage-stage embryo is associated with increased risks of LBW and SGA births.
Elevated circulating homocysteine concentrations delayed nerve conduction velocity and increase the risk of diabetic kidney disease in patients with type 2 diabetes
Authors: Lv Nannan , Jia Luzhu , Liu Fei , Cheng Lan , Liu Feng , Kuang Jinsong , Chen Xin
Published: December 2024

Introduction

China has the largest population of individuals with diabetes, and the prevalence of various complications among patients with type 2 diabetes remains high. Diabetic nephropathy affects approximately 20% to 40% of diabetic patients, becoming a major cause of chronic kidney disease and end-stage renal disease. Furthermore, around 50% of patients develop diabetic peripheral neuropathy (DPN), which is closely associated with physical disability, increased healthcare costs, and reduced work productivity. There is an urgent need for novel strategies in prevention, diagnosis, and treatment to improve patient outcomes.

Methods

In this study, 163 patients with type 2 diabetes were selected as the observation group and further divided into three subgroups based on homocysteine (HCY) levels. The study measured several clinical parameters, including homocysteine, blood glucose, blood lipids, glycated hemoglobin, urinary microalbumin, urinary albumin-to-creatinine ratio (ACR), electromyography, and highly-sensitive C-reactive protein (CRP), among others. The levels of these indicators were analyzed and compared across the subgroups.

Results

The results revealed significant differences in uric acid, creatinine, urinary microalbumin, urinary ACR, and nerve conduction velocity (right tibial nerve sensory conduction) among different HCY levels in patients with type 2 diabetes (P < 0.05). Linear regression analysis indicated that homocysteine levels were associated with systolic blood pressure, glycated hemoglobin, fasting C-peptide, uric acid, creatinine, urinary microalbumin, and nerve conduction velocity (including motor conduction velocity of the ulnar nerve and sensory conduction velocity of the sural nerve).

Discussion

The clinical assessment of homocysteine in diabetic patients holds significant importance in the prevention of microvascular complications. Lowering HCY levels may offer a promising therapeutic approach for managing microvascular disease in diabetes.
Unveiling risk factors for post-COVID-19 syndrome development in people with type 2 diabetes
Authors: Matviichuk Anton , Yerokhovych Viktoriia , Zemskov Sergii , Ilkiv Yeva , Gurianov Vitalii , Shaienko Zlatoslava , Falalyeyeva Tetyana , Sulaieva Oksana , Kobyliak Nazarii
Published: December 2024

Introduction

Post-COVID-19 syndrome (PCS) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated chronic condition characterized by long-term violations of physical and mental health. People with type 2 diabetes (T2D) are at high risk for severe COVID-19 and PCS.

Aim

The current study aimed to define the predictors of PCS development in people with T2D for further planning of preventive measures and improving patient outcomes.

Materials and methods

The data were collected through the national survey targeting persons with T2D concerning the history of COVID-19 course and signs and symptoms that developed during or after COVID-19 and continued for more than 12 weeks and were not explained by an alternative diagnosis. In total, 469 patients from different regions of Ukraine were enrolled in the study. Among them, 227 patients reported PCS development (main group), while 242 patients did not claim PCS symptoms (comparison group). Stepwise multivariate logistic regression and probabilistic neural network (PNN) models were used to select independent risk factors.

Results

Based on the survey data, 8 independent factors associated with the risk of PCS development in T2D patients were selected: newly diagnosed T2D (OR 4.86; 95% CI 2.55–9.28; p<0.001), female sex (OR 1.29; 95% CI 0.86–1.94; p=0.220), COVID-19 severity (OR 1.35 95% CI 1.05–1.70; p=0.018), myocardial infarction (OR 2.42 95% CI 1.26–4.64; p=0.002) and stroke (OR 3.68 95% CI 1.70–7.96; p=0.001) in anamnesis, HbA1c above 9.2% (OR 2.17 95% CI 1.37–3.43; p=0.001), and the use of insulin analogs (OR 2.28 95% CI 1.31–3.94; p=0.003) vs human insulin (OR 0.67 95% CI 0.39–1.15; p=0.146). Although obesity aggravated COVID-19 severity, it did not impact PCS development. In ROC analysis, the 8-factor multilayer perceptron (MLP) model exhibited better performance (AUC 0.808; 95% CІ 0.770–0.843), allowing the prediction of the risk of PCS development with a sensitivity of 71.4%, specificity of 76%, PPV of 73.6% and NPV of 73.9%.

Conclusions

Patients who were newly diagnosed with T2D, had HbA1c above 9.2%, had previous cardiovascular or cerebrovascular events, and had severe COVID-19 associated with mechanical lung ventilation were at high risk for PCS.
Association between thyroid hormone sensitivity and carotid plaque risk: a health examination cohort-based study
Authors: Gong Rui , Wang Shi , Ding Hongqiong , Yu Lixia , Xu Ming , Xu Sanping , Ling Yan
Published: December 2024

Introduction

The involvement of thyroid hormone in cardiovascular disease remains debated. The aim of our research was to ascertain whether thyroid hormone sensitivity indices are related to carotid plaque (CAP) risk in the general population.

Methods

We recruited 5,360 participants for health examinations to explore the correlation between thyroid hormone sensitivity indices and CAP risk. We then compared baseline characteristics of participants with CAP to those without CAP based on multivariate logistic regression analysis. Additionally, we conducted subgroup analyses stratified by gender and age to further elucidate this relationship.

Results

Among the 5,360 participants, 1,055 (19.7%) were diagnosed with CAP. After adjusting for various confounding factors, our results showed a positive association between CAP risk and the indices (TFQI, PTFQI, TSHI, and TT4RI). Conversely, the FT3/FT4 ratio showed a negative correlation with CAP risk. Sex-based subgroup analysis revealed a stronger correlation between thyroid hormone sensitivity and CAP in females compared to males. In the age subgroup, the significant association was observed in older individuals (age >60) compared to middle-aged participants (age ≤60).

Conclusion

Our study suggests a significant correlation between thyroid hormone sensitivity and CAP, particularly in females and participants over the age of 60.
Association between arthropathies and postpartum hemorrhage: a bidirectional Mendelian randomization study
Authors: Wu Zhao , Yuan Chengyu , Peng Xue
Published: December 2024

Background

Research links arthropathies with adverse pregnancy outcomes. This study aims to explore its connection to postpartum hemorrhage (PPH) through Mendelian randomization (MR) analysis.

Methods

The study used GWAS data from the IEU OpenGWAS database for PPH and arthropathies. After selecting instrumental variables, bidirectional MR analysis was conducted using MR-Egger, Weighted median, Simple mode, Weighted mode, and IVW methods. Sensitivity analysis was then performed to assess MR results reliability. Finally, enrichment analysis of genes corresponding to arthropathies SNPs in forward MR was conducted to explore their biological function and signaling pathways.

Results

The forward MR results revealed that arthropathies was causally related to PPH, and arthropathies was a risk factor for PPH. Whereas, there was not a causal relationship between PPH and arthropathies by reverse MR analysis. It illustrated the reliability of the MR analysis results by the sensitivity analysis without heterogeneity, horizontal pleiotropy, and SNPs of severe bias by LOO analysis. Furthermore, a total of 33 genes corresponding to SNPs of arthropathies were obtained, which were mainly enriched in regulation of response to biotic stimulus, spliceosomal snRNP complex and ligase activity in GO terms, and natural killer cell-mediated cytotoxicity in KEGG pathways.

Conclusion

This study supported that arthropathies was a risk factor for PPH, and the pathways involved the genes corresponding to SNPs were analyzed, which could provide important reference and evidence for further exploring the molecular mechanism between arthropathies and PPH.
Widening the infantile hypotonia with psychomotor retardation and characteristic Facies-1 Syndrome’s clinical and molecular spectrum through NALCN in-silico structural analysis
Authors: Vecchio Davide , Macchiaiolo Marina , Gonfiantini Michaela V. , Panfili Filippo M. , Petrizzelli Francesco , Liorni Niccolò , Cortellessa Fabiana , Sinibaldi Lorenzo , Rana Ippolita , Agolini Emanuele , Cocciadiferro Dario , Colantoni Nicole , Semeraro Michela , Rizzo Cristiano , Deodati Annalisa , Cotugno Nicola , Caggiano Serena , Verrillo Elisabetta , Nucci Carlotta G. , Alkan Serpil , Saraiva Jorge M. , De Sá Joaquim , Almeida Pedro M. , Krishna Jayanth , Buonuomo Paola S. , Martinelli Diego , Dionisi Vici Carlo , Caputo Viviana , Bartuli Andrea , Novelli Antonio , Mazza Tommaso
Published: December 2024

Introduction

Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1, MIM#615419) is a rare, birth onset, autosomal recessive disorder caused by homozygous or compound heterozygous truncating variants in NALCN gene (MIM#611549) resulting in a loss-of-function effect.

Methods

We enrolled a new IHPRF1 patients’ cohort in the framework of an international multicentric collaboration study. Using specialized in silico pathogenicity predictors and ad hoc structural analyses, we assessed the mechanistic consequences of the deleterious variants retrieved on NALCN structure and function.

Results

To date 38 different NALCN variants have been retrieved from 33 different families, 26 from unrelated and 22 from related patients. We report on five new IHPRF1 patients from four different families, harboring four newly identified and one previously retrieved variant that exhibited a markedly significant functional impact, thereby compromising the functionality of the protein complex.

Discussion

By widening the functional spectrum of biallelic variants affecting the NALCN gene, this article broadens the IHPRF1 syndrome’s genotype-phenotype correlation and gives new insight into its pathogenic mechanism, diagnosis, and clinical management.
Unraveling metabolic signatures in SARS-CoV-2 variant infections using multiomics analysis
Authors: Lee Sunho , Lee Jueun , Lyoo Kwang-Soo , Shin Yourim , Shin Dong-Min , Kim Jun-Won , Yang Jeong-Sun , Kim Kyung-Chang , Lee Joo-Yeon , Hwang Geum-Sook
Published: December 2024

Introduction

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, notably delta and omicron, has significantly accelerated the global pandemic, worsening conditions worldwide. However, there is a lack of research concerning the molecular mechanisms related to immune responses and metabolism induced by these variants.

Methods

Here, metabolomics combined with transcriptomics was performed to elucidate the immunometabolic changes in the lung of hamsters infected with delta and omicron variants.

Results

Both variants caused acute inflammation and lung pathology in intranasally infected hamsters. Principal component analysis uncovered the delta variant significantly altered lung metabolite levels between the pre- and post-infection states. Additionally, metabolic pathways determined by assessment of metabolites and genes in lung revealed significant alterations in arginine biosynthesis, glutathione metabolism, and tryptophan metabolism upon infection with both variants and closely linked to inflammatory cytokines, indicating immune activation and oxidative stress in response to both variants. These metabolic changes were also evident in the serum, validating the presence of systemic alterations corresponding to those identified in lung. Notably, the delta variant induced a more robust metabolic regulation than the omicron variant.

Discussion

The study suggests that multi-omics is a valuable approach for understanding immunometabolic responses to infectious diseases, and providing insights for effective treatment strategies.
Linsitinib inhibits proliferation and induces apoptosis of both IGF-1R and TSH-R expressing cells
Authors: Luffy Maximilian , Ganz Anna-Lena , Wagner Stefanie , Wolf Jan , Ropertz Julian , Zeidan Ryan , Kent Jeffrey D. , Douglas Raymond S. , Kahaly George J.
Published: December 2024

Background

The insulin-like growth factor 1 receptor (IGF-1R) and the thyrotropin receptor (TSH-R) are expressed on orbital cells and thyrocytes. These receptors are targeted in autoimmune-induced thyroid eye disease (TED). Effective therapeutic treatment of TED inhibits activation of the IGF-1R/TSH-R complex.

Methods

The inhibitory effect on cell proliferation of a small molecule targeting IGF-1R phosphorylation (Linsitinib) was investigated in an IGF-1R expressing cell line and a Chinese Hamster Ovary (CHO) cell line overexpressing TSH-R. An IGF-1R monoclonal antibody antagonist, Teprotumumab served as control. Both cell lines were plated in a 96-well format and treated with both compounds for 24 hours. After addition of tetrazolium, absorbance was measured. The apoptosis marker caspase-3/7 activity was measured. The half-maximal inhibitory concentration (IC50) of TSH-R-Ab induced stimulation (stimulatory monoclonal antibody, mAb, M22) of the TSH-R cell line was evaluated with a cell-based bioassay for blocking TSH-R-Ab. Cells were treated with ten rising concentrations of either Linsitinib, Linsitinib + Metformin, Teprotumumab, or a blocking TSH-R mAb (K1-70).

Results

Linsitinib strongly inhibited the proliferation of both cell lines at several concentrations: 31,612.5 ng/mL (IGF-1R cell line -78%, P=0.0031, TSH-R cell line -75%, P=0.0059), and at 63,225 ng/mL (IGF-1R cell line -73%, P=0.0073, TSH-R cell line -73%, P=0.0108). Linsitinib induced apoptosis of both cell lines, both morphologically confirmed and with an increased caspase-3/7 activity at concentrations of 31,612.5 ng/mL (IGF-1R cell line P=0.0158, TSH-R cell line P=0.0048) and 63,225 ng/mL (IGF-1R cell line P=0.0005, TSH-R cell line P=0.0020). Linsitinib markedly inhibited proliferation of the IGF-1R cell line at all concentrations compared to Teprotumumab (P=0.0286). Teprotumumab inhibition was significant only at 15,806.25 ng/mL with the TSH-R cell line (-15%, P=0.0396). In addition, in the TSH-R-Ab blocking bioassay, Linsitinib and the tested compounds demonstrated strong inhibition across all ten dilutions (100%).

Conclusions

Linsitinib effectively induces apoptosis and inhibits proliferation of both IGF-1R and TSH-R expressing target cells, therefore demonstrating its therapeutic potential to block the reported crosstalk of the two mediators in autoimmune TED.
Targeting inerleukin-6 for renoprotection
Authors: Gubernatorova Ekaterina O. , Samsonov Mikhail Y. , Drutskaya Marina S. , Lebedeva Svetlana , Bukhanova Darya , Materenchuk Maria , Mutig Kerim
Published: December 2024

Sterile inflammation has been increasingly recognized as a hallmark of non-infectious kidney diseases. Induction of pro-inflammatory cytokines in injured kidney tissue promotes infiltration of immune cells serving to clear cell debris and facilitate tissue repair. However, excessive or prolonged inflammatory response has been associated with immune-mediated tissue damage, nephron loss, and development of renal fibrosis. Interleukin 6 (IL-6) is a cytokine with pleiotropic effects including a major role in inflammation. IL-6 signals either via membrane-bound (classic signaling) or soluble receptor forms (trans-signaling) thus affecting distinct cell types and eliciting various metabolic, cytoprotective, or pro-inflammatory reactions. Antibodies neutralizing IL-6 or its receptor have been developed for therapy of autoimmune and chronic non-renal inflammatory diseases. Small molecule inhibitors of Janus kinases acting downstream of the IL-6 receptor, as well as recombinant soluble glycoprotein 130 variants suppressing the IL-6 trans-signaling add to the available therapeutic options. Animal data and accumulating clinical experience strongly suggest that suppression of IL-6 signaling pathways bears therapeutic potential in acute and chronic kidney diseases. The present work analyses the renoprotective potential of clinically relevant IL-6 signaling inhibitors in acute kidney injury, chronic kidney disease, and kidney transplantation with focus on current achievements and future prospects.
Cross-language orthographic neighborhood density effects in Dutch–English and Spanish–English bilinguals
Authors: Biedermann Britta , Beyersmann Elisabeth , Blosfelds Mara , Macapagal Christella , Rosevear Ashleigh , Marinovic Welber
Published: December 2024

Processing a word in a second language (L2) may be hindered or helped by the simultaneous activation of similar words present in L2 and in addition by similar words that occur in the first language (L1). Precise mechanisms for influencing variables within L2 and cross-language processing are still little understood. The current visual word recognition study explored orthographic neighborhood density (ND) effects in L2 English, replicating the effects for Dutch–English while expanding the exploration to a new language combination, Spanish–English. The within- and across-language effects were explored in a group of Dutch–English and Spanish–English bilinguals. English L2 targets were subdivided into four ND conditions: high L1 + high L2, high L1 + low L2, low L1 + high L2, and low L1 + low L2. For Experiment 1, an analysis of generalized linear mixed-effects models (GLMMs) revealed that Dutch (L1)–English (L2) bilinguals showed a facilitatory main effect of English ND on reaction times and error rates. However, an inhibitory main effect of L1 Dutch ND on L2 visual word recognition was only observed for reaction times, not error rates. Overall, no interaction was detected between L1 and L2 NDs for reaction times or error rates. Additionally, a factorial permutation test confirmed the L2 facilitatory effect on both reaction times and error rates, while it supported an L1 inhibitory effect for error rates only. In Experiment 2, a GLMM analysis replicated the L2 facilitatory effect on reaction times in Spanish (L1)–English (L2) bilinguals but did not reveal an inhibitory main effect of L1 on L2 word recognition. Instead, we found a significant interaction between English (L2) and Spanish (L1) ND. Reaction time patterns were confirmed by the non-parametric analysis, although with only a marginally significant interaction. For error rates, no effect for ND was detected using GLMMs. However, the permutation test revealed significant L2 facilitatory and L1 inhibitory effects on L2 word recognition but no significant interaction. Our data confirm a robust L2 facilitatory main effect of ND on reaction times across experiments and analyses, while L1 inhibitory main and interaction effects were less robust across experiments and analyses. The latter may be dependent on language specificity and speaker characteristics.
Risk performance analysis model of escort operation in Arctic waters via an integrated FRAM and Bayesian network
Authors: Li Zhuang , Zhu Xiaoming , Liao Shiguan , Gao Kaixian , Hu Shenping
Published: December 2024

Escort operation is an effective mean to ensure the safety of ship navigation in the Arctic ice area and expand the window period for ship navigation. At the same time, the operation mode between icebreaker and escorted ship may also causes collision accident. In order to scientifically reflect the complex coupling relationship in the escort operation system in Arctic waters and effectively manage the navigation risks. This study proposes to use the functional resonance analysis method (FRAM) to identify the risk factors of ship escort operation in Arctic waters, and uses the Bayesian network (BN) method to establish a risk assessment model for escort operation collision accident. The cloud model is used to process the uncertain data information. The proposed method is applied during the actual escort operation of a commercial ship on the Arctic Northeast Passage. According to the model simulation results, the risk performance of ship escort operation in Arctic waters is quantitatively analyzed, and the key risk causes are further analyzed. This study has positive significance for better understanding the risk evolution mechanism of ship escort operation in Arctic ice area and helping relevant management departments to take risk control measures.