bluuebunny/crossref_metadata_2025 huggingface dataset:
Back to the Future: Revisiting Nonpremixed Designs for Fuel Flexible (H2/NH3/CH4), Low NOx Combustion
Authors:   Georgia Institute of Technology, Patel Shivam J. , Noble David R. ,   Electric Power Research Institute, Emerson Benjamin L. ,   Georgia Institute of Technology, Lieuwen Timothy C. ,   Georgia Institute of Technology
Published: October 2024

The future of the energy sector requires highly flexible gas turbines that can adapt to a dynamic energy environment. These gas turbines must accommodate a wide range of fuels across a large operating envelope, including natural gas, hydrogen, and ammonia. State-of-the-art gas turbines for power generation have all adopted lean premixed (LPM) combustion strategies as the de facto method to reduce NOx emissions. However, their premixed nature inherently limits their fuel- and operational flexibility. Reverting to non-premixed combustion, the dominant legacy technology before the advent of LPM, would regain much of this flexibility. However, this must be done without sacrificing the low-NOx benefits of modern LPM engines. This paper explores the NOx emissions of a novel Non-premixed Rich Relaxation Lean (NRRL) combustor across various fuels: CH4, NH3, and H2. We demonstrate emissions and performance characteristics via chemical reactor network modeling and compare them to LPM ones at equivalent operating conditions. All these fuels achieve similarly low NOx levels with this concept. H2 decreases the residence time requirements, without a significant impact on exit NOx. NRRL NOx levels are as low as or lower than comparable LPM systems and have dramatically lower sensitivities to pressure or temperature.
Numerical simulation of flow characteristics and heat transfer in ribbed channel using gas method
Authors:   School of Energy and Power Engineering, Beihang University National Key Laboratory of Science and Technology on Aero-Engine Aero- Thermodynamics, Beihang University, Liu Yangwei , Wang Guangyu ,   School of Energy and Power Engineering, Beihang University National Key Laboratory of Science and Technology on Aero-Engine Aero- Thermodynamics, Beihang University, Tang Yumeng ,   School of Energy and Power Engineering, Beihang University National Key Laboratory of Science and Technology on Aero-Engine Aero- Thermodynamics, Beihang University
Published: October 2024

Ribbed channel is widely used in internal cooling of engineering, especially in turbine blades. The flow passing through a rib is typically characterized by flow separation and reattachment, which can significantly enhance the heat transfer. Accurate numerical simulation of such flow and heat transfer characteristics has profound engineering significance. The grid-adaptive simulation (GAS) method, as a novel hybrid Reynolds-averaged Navier–Stokes (RANS) and large-eddysimulation (LES) method, can further reduce computational costs while ensuring high accuracy. In this study, the GASSST model has been applied to predict flow and heat transfer in ribbed channel. Firstly, sensitive studies of the GAS model are thoroughly performed across three computational meshes with varying resolutions. Then, the widely used hybrid RANS-LES methods are selected for comparison, including scale-adaptive simulation (SAS) and delayed detached-eddy simulation (DDES). Results indicate that GAS-SST demonstrates robust grid-adaptive ability in predicting the flow and heat transfer characteristics in ribbed channel flow under different grid resolutions. GAS method can alleviate the conventional gray area problem associated with hybrid RANS-LES methods, and it accurately predicts the mean flow fields, turbulent characteristics, mean thermal fields, and heat transfer characteristics in ribbed channel flow, aligning closely with experimental results. Overall, GAS method demonstrates superior capability in predicting the ribbed channel flow under low grid resolution, and shows great potential for accurately predicting heat transfer.
PENGARUH KUALITAS PRODUK, HARGA, DAN PROMOSITTERHADAPKKEPUTUSAN PEMBELIAN SMARTPHONE VIVO (STUDI KASUS REE ONE CELL)
Authors: Pradistya Vionetta Nuriana , Santoso Rohmad Prio
Published: October 2024

Penelitian ini bertujuan mengetahui pengaruh kualitas produk, harga, dan promosi terhadap keputusan pembelian. Obyek dari penelitian ini adalah toko Ree one cell Jombang. Penelitian ini menggunakan Teknik nonprobability sampling dengan teknik pengambilan sampel menggunakan sampling jenuh berjumlah 90 responden. Hasil penelitian menunjukkan bahwa: (1) Kualitas produk berpengaruh secara signifikan dan positif parsial terhadap keputusan pembelian produk smartphone vivo (studi kasus konsumen toko Ree one cell jombang). (2) Harga berpengaruh secara signifikan dan positif parsial terhadap keputusan pembelian produk smartphone vivo (studi kasus konsumen toko Ree one cell Jombang). (3) Promosi berpengaruh secara signifikan dan positif parsial terhadap keputusan pembelian produk smartphone vivo (studi kasus konsumen toko Ree one cell Jombang). (4) Kualitas produk, harga, dan promosi secara bersama-sama berpengaruh secara simultan dan signifikan terhadap keputusan pembelian produk smartphone vivo (studi kasus konsumen toko Ree one cell jombang)
PENGARUH LINGKUNGAN KERJA DAN KOMUNIKASI TERHADAP PRODUKTIVITAS KERJA KARYAWAN DI CV. TIGA AGUNG JOMBANG
Authors: A’izzah Qismatul , Anah Lik
Published: October 2024

Penelitian ini bertujuan untuk mengetahui pengaruh lingkungan kerja dan komunikasi terhadap produktivitas kerja pada CV.Tiga Agung Jombang. Metode yang digunakan pada penelitian ini adalah metode kuantitatif dengan jenis penilitian asosiatif. Jumlah sampel sebanyak 100 karyawan dengan menggunakan sampel jenul atau sampel total. Teknik pengumpulan data menggunakan kuesioner. Analisis yang digunakan yaitu analisis linier berganda dengan bantuan software SPSS 25. Hasil penelitian ini menunjukan bahwa: (1) lingkungan kerja tidak berpengaruh terhadap produktivitas kerja karyawan CV. Tiga Agung Jombang dilihat dari nilai thitung lebih Kecil dari ttabel yaitu 0,907<1,9847 dan nilai signifikan 0,367. (2) terdapat pengaruh komunikasi terhadap produktivitas kerja karyawan CV. Tiga Agung Jombang Dengan nilai thitung lebih besar dari ttabel 7,290>1,9847 dan nilai signifikasi 0,000. (3) lingkungan kerja dan komunikasi secara simultan berpengaruh terhadap produktivitas kerja karyawan CV.Tiga agung Jombang sebesar 54.115.
Clientelistic Linkage Mechanisms in Post-Communist Democracies 2009-2023. DALP Evidence
Authors: Bliznakovski Jovan
Published: October 2024

This paper presents initial findings from the expert survey data collection conducted as part of the Democratic Accountability and Linkages Project (DALP) during 2022-2024, with a focus on post-communist democracies. The study examines the prevalence and interplay of political clientelism and programmatism—two key partisan mobilization strategies—across the region. Utilizing data from DALP I (2008-2009) and DALP II (2022-2024), the paper explores the progression of these strategies over time. Additionally, the analysis investigates partisan reliance on different sub-strategies of clientelism—specifically electoral and relational—and their relationship with various voter groups, drawing on data from DALP II. The findings reveal significant variation in the mobilization profiles of both party systems and political parties, with some major parties effectively combining clientelism and programmatism. Notably, relational clientelism emerges as the dominant form of linkage in clientelistic politics within the post-communist space, overshadowing the more globally researched exchange of benefits for electoral services.
Dysfunctional lens syndrome: a literature review
Authors: Borisov F. G. , Loskutov I. A.
Published: October 2024

Introduction. The term “Dysfunctional Lens Syndrome” (DLS) refers to age-related changes in the lens, including early cataracts and presbyopia, that do not significantly reduce visual acuity. This syndrome is characterized by a decrease in accommodative amplitude, an increase in light scattering, and a reduction in contrast sensitivity. With rising life expectancy, the prevalence of DLS is increasing, necessitating a more in-depth study of the pathogenic mechanisms underlying the syndrome and the refinement of its diagnostic criteria to establish standards for treatment correction. Aim: to summarize information on the pathogenesis of DLS, the potential for staging the syndrome using objective examination methods, and to provide treatment recommendations. Materials and methods. A bibliographic study of scientific publications was conducted using the Pubmed, ScienceDirect, and Cyberleninka databases. Literature sources were searched using the following keywords: dysfunctional lens syndrome (DLS), presbyopia correction, cataract, age-related lens changes. A total of 32 publications, primarily from the last 10 years, were included in the study from more than 100 viewed sources. Results. The DLS encompasses a wide range of conditions, from early stages characterized by a loss of accommodative amplitude and minor refractive anomalies to later stages involving a decrease in visual acuity and quality due to increased light scattering and aberrations. Currently, the evaluation of age-related lens changes involves assessing visual acuity and determining the degree of lens opacification using slit-lamp examination. Additionally, objective instrumental methods, such as optical coherence tomography and Scheimpflug imaging, can be used to assess the degree of lens opacification. Various methods are employed for the correction and treatment of DLS, ranging from glasses and contact lenses to surgical interventions, such as lens extraction and intraocular lens implantation. Research is also ongoing into drugs aimed at slowing the progression of lens changes. Conclusion. The term “Dysfunctional Lens Syndrome” is currently used to describe early cataracts and presbyopia, where the reduction in visual acuity is still minor, but patients experience visual complaints due to age-related lens changes. Further research is necessary to develop and standardize diagnostic criteria and to evaluate the effectiveness of new treatment methods and interventions in order to create the most effective and adequate approach to correcting DLS and alleviating the associated visual complaints.
Penerapan Neural Network sebagai Klasifikasi Kualitas Air Hasil Filtrasi Reverse Osmosis
Authors: Muhammad Dzi Washfil Hasin  , Didik Sukoco  , Ii Munadhif
Published: October 2024

Air adalah unsur yang tak tergantikan dan penting bagi kehidupan, termasuk manusia yang memerlukan air berkualitas sesuai dengan standar kimia, fisika, dan biologi. Penelitian ini bertujuan untuk menguji dan mengklasifikasikan kualitas air hasil filtrasi reverse osmosis (RO) menggunakan metode Neural Network. Air waduk yang telah difiltrasi diuji dengan tiga sensor yang mendeteksi total kepadatan terlarut, pH, dan konduktivitas listrik (EC), dengan data dikirim ke modul ESP32 dan ditampilkan pada LCD. Neural Network digunakan untuk menganalisis kandungan air berdasarkan parameter yang sesuai dengan Permenkes Nomor 2 Tahun 2023 dan Peraturan Pemerintah Republik Indonesia Nomor 22 Tahun 2021. Hasil pengujian dibandingkan dengan standar baku mutu air untuk menentukan kategori kualitas air. Dari 15 percobaan, sistem klasifikasi menunjukkan hasil yang merata: 7 percobaan untuk kategori 1, 4 untuk kategori 2, dan 4 untuk kategori 3. Temuan ini menunjukkan potensi yang baik dalam penerapan Neural Network pada sistem filtrasi RO untuk menangani variasi data yang kompleks.
Lessons from External Quality Control in Laboratory Medicine: Important Implications for Public Health!
Authors: Norris Douglas , Schellenberg Ingo
Published: October 2024

Data on the general impact of the quality of laboratory testing on public health and patient care are scarce despite the fact that billons of tests worth trillions of dollars are performed each year around the world both, in the medical inpatient and outpatient sector. This remains true also because medical testing remains largely underregulated in many parts of the world and most internal quality control materials are provided by the manufacturers themselves, and the majority of medical tests have not been evaluated further concerning their validity by sound clinical studies. This is why external quality control measures including round robin trials and external quality control surveys are so important in assessing the quality of modern assays. Moreover, better insight is needed into the many areas of in vitro diagnostics and into the cornucopia of problems with test quality in the different areas of laboratory medicine, and the impact of such problems on medical care and the public health sector. This Research Topic is focused on possible lessons to be learned from the continuous work of INSTAND, e.V., Duesseldorf, an independent scientific society, devoted to the complex field of external quality control in laboratory medicine over the past 20 years. This includes, but is not limited to, the areas of regulatory issues in molecular diagnostics, and external quality control in connection with the identification of diagnostic and therapeutic tools for clinical use. As such, this article collection aims to accumulate better knowledge on the ongoing problems and pitfalls with insufficiently evaluated test systems and the possible impact of such problems on medical care and public health. Findings from the different studies included in this special issue will pave the way for a better understanding related to the impact of test quality on patient care on the individual level and at large, to help improving future medical care and high quality patient management.
Comparative analysis of porcine-uterine decellularization for bioactive-molecule preservation and DNA removal
Authors: Fazel Anvari Yazdi Abbas , Tahermanesh Kobra , Ejlali Maryam , Babaei-Ghazvini Amin , Acharya Bishnu , Badea Ildiko , MacPhee Daniel J. , Chen Xiongbiao
Published: October 2024

Introduction

Decellularized uterine extracellular matrix has emerged as a pivotal focus in the realm of biomaterials, offering a promising source in uterine tissue regeneration, research on disease diagnosis and treatments, and ultimately uterine transplantation. In this study, we examined various protocols for decellularizing porcine uterine tissues, aimed to unravel the intricate dynamics of DNA removal, bioactive molecules preservation, and microstructural alterations.

Methods

Porcine uterine tissues were treated with 6 different, yet rigorously selected and designed, protocols with sodium dodecyl sulfate (SDS), Triton® X-100, peracetic acid + ethanol, and DNase I. After decellularization, we examined DNA quantification, histological staining (H&E and DAPI), glycosaminoglycans (GAG) assay, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and Thermogravimetric Analysis (TGA).

Results

A comparative analysis among all 6 protocols was conducted with the results demonstrating that all protocols achieved decellularization; while 0.1% SDS + 1% Triton® X-100, coupled with agitation, demonstrated the highest efficiency in DNA removal. Also, it was found that DNase I played a key role in enhancing the efficiency of the decellularization process by underscoring its significance in digesting cellular contents and eliminating cell debris by 99.79% (19.63 ± 3.92 ng/mg dry weight).

Conclusions

Our findings enhance the nuanced understanding of DNA removal, GAG preservation, microstructural alteration, and protein decomposition in decellularized uterine extracellular matrix, while highlighting the importance of decellularization protocols designed for intended applications. This study along with our findings represents meaningful progress for advancing the field of uterine transplantation and related tissue engineering/regenerative medicine.
Protocol for unifying cross-chain liquidity on polkadot
Authors: Valaštín Viktor , Morháč Dušan , Košťál Kristián , Kotuliak Ivan
Published: October 2024

Liquidity is critical for a healthy and thriving blockchain ecosystem, enabling value exchange between participants. However, achieving unified liquidity across heterogeneous blockchain platforms remains challenging due to disparities in architecture, virtual machines, and asset management logic. These disparities force assets to be wrapped into other formats to ensure compatibility with underlying systems, thus fragmenting liquidity into multiple pools. This paper proposes LiquiSpell, a novel protocol that aims to unify liquidity across multiple parachains within the Polkadot ecosystem. By leveraging the cross-chain message passing (XCMP), LiquiSpell introduces the concept of a universal transaction that can be constructed to be compatible with any parachain, regardless of its underlying architecture or asset management pallet. This approach overcomes the obstacles posed by the diverse nature of parachains, enabling seamless asset sharing and enhancing cross-chain interoperability. The proposed solution mitigates liquidity fragmentation within the Polkadot ecosystem. It presents a framework that can be extended to other multichain environments outside Polkadot. Ultimately, LiquiSpell aims to foster a thriving ecosystem by facilitating the introduction of new assets and increasing overall liquidity, thereby driving innovation and adoption within the decentralized finance (DeFi) landscape.
Decoding persuasion: a survey on ML and NLP methods for the study of online persuasion
Authors: Bassi Davide , Fomsgaard Søren , Pereira-Fariña Martín
Published: October 2024

The proliferation of digital communication has profoundly transformed the landscape of persuasive discourse. Online platforms have amplified the reach and impact of persuasive techniques. However, they have also enabled the rapid spread of manipulative content, targeted propaganda, and divisive rhetoric. Consequently, a wide range of computational approaches has emerged to address the multifaceted nature of digital persuasion, to detect and mitigate its harmful practices. In light of this, the paper surveys computational methods for detecting persuasive means in digital communication, focusing on how they integrate humanistic knowledge to operationalize this construct. Additionally, special emphasis is placed on models' explainability, a pivotal aspect considering these models are used by institutions to influence societal interactions. For the analysis, two primary perspectives in persuasion are defined: linguistic and argumentative. The linguistic approach analyzes specific textual features, allowing for highly accountable algorithms based on explicit rules. The argumentative approach focuses on broader persuasive mechanisms, offering greater scalability but often resulting in less explainable models due to their complexity. This tension between model sophistication and explainability presents a key challenge in developing effective and transparent persuasion detection systems. The results highlight the spectrum of methodologies for studying persuasion, ranging from analyzing stylistic elements to detecting explicitly propagandist messages. Our findings highlight two key challenges in using these algorithms to tackle societal issues of persuasion misuse: the opacity of deep learning models and the absence of a theoretically grounded distinction between vicious and virtuous persuasion. To address these challenges, we propose integrating social sciences and humanities theories to enhance the effectiveness and ethical robustness of persuasion detection systems. This interdisciplinary approach enables a more nuanced characterization of text, facilitating the differentiation between vicious and virtuous persuasion through analysis of rhetorical, argumentative, and emotional aspects. We emphasize the potential of hybrid approaches that combine rule-based methods with deep learning techniques, as these offer a promising avenue for implementing this interdisciplinary framework. The paper concludes by outlining future challenges, including the importance of multimodal and multilingual analysis, ethical considerations in handling user-generated data and the growing challenge of distinguishing between human and AI-generated persuasive content.
Do social cognitive factors influence final-year undergraduate students’ intentions to pursue advanced degrees? An examination of the moderating effect of sex
Authors: Bayon Chembelyn , Abejo Maximino , Guinocor Marvin , Garciano Martha Joyce , Literatus Jonita , Reveche Shaleen Jean , Nudalo Arnel , Gonzaga Maria Cristina , Caminos Israeli , Caminos Roger , Borres Vincent , Cortes Sylvester
Published: October 2024

This study explores the factors influencing final-year undergraduate students’ intentions to pursue advanced degrees through the lens of social cognitive theory (SCT). In addition, it investigates the moderating effect of sex on the causal pathways in the proposed model. Using a quantitative cross-sectional survey design, 578 final-year undergraduate students from various degree programs participated in an online survey. The results revealed that outcome expectations and social support are significant predictors of intention, while intention itself predicts the implementation of intentions to pursue an advanced degree. However, self-efficacy was not found to influence intention, and sex did not moderate the hypothesized paths in the model. These findings suggest that SCT provides a useful and robust framework for understanding the factors shaping undergraduate students’ intentions to pursue advanced degrees, as evidenced by the high explanatory power of the structural model. The study also offers practical and theoretical implications, along with suggestions for future research.
The influence of adult urine lead exposure on bone mineral densit: NHANES 2015-2018
Authors: Wang Shaokang , Zhao Xiaofeng , Zhou Runtian , Jin Yuanzhang , Wang Xiaonan , Ma Xiaotian , Lu Xiangdong
Published: October 2024

Introduction

Previous studies have indicated that exposure to heavy metals related to bone health is primarily limited to some common harmful metals, and the impact of lead has not been fully understood. This study aims to explore the relationship between urine lead exposure and bone density.

Methods

1,310 adults were included from the NHANES database (2015-2018), and through generalized linear regression analysis and constrained cubic spline models, the association between lead levels and total bone density as well as lumbar spine bone density was explored. The study also examined the impact of combined exposure to lead and cadmium on bone density.

Results and conclusions

Urinary lead levels were significantly negatively correlated with total bone mineral density (β: −0.015; 95%CI: −0.024, −0.007) and lumbar spine bone mineral density (β: −0.019; 95%CI: −0.031, −0.006). Compared to the lowest three quartiles of lead levels, the adjusted odds ratios for T3 changes in total bone mineral density and lumbar spine bone mineral density were 0.974 (95%CI: 0.959, 0.990) and 0.967 (95%CI: 0.943, 0.991), indicating a significant negative trend. Further analysis with constrained cubic spline models revealed a non-linear decreasing relationship between urinary lead and total bone mineral density as well as lumbar spine bone mineral density. Stratified analyses suggested that the relationship between urinary lead levels and bone mineral density might be significantly influenced by age, while gender showed no significant impact on the relationship. Moreover, combined exposure to lead and cadmium was found to be associated with decreased bone mineral density, emphasizing the potential synergistic effects between lead and cadmium on bone health. However, the specific mechanisms of lead and its effects on different populations require further comprehensive research. This study provides valuable insights for further exploration and development of relevant public health policies.
A biochar-based amendment improved cadmium (Cd) immobilization, reduced its bioaccumulation, and increased rice yield
Authors: Han Junnan , Wu Donghai , Yang John , Shi Yuan , Abid Ghassen , Wang Lingjun , Li Zhengguo
Published: October 2024

Cadmium (Cd) contamination of soil threatens human health, food security, and ecosystem sustainability. The in situ stabilization of Cd has been recognized as a potentially economical technology for the remediation of Cd-contaminated soil. Recently, biochar (BC) and activated carbon (AC) have received widespread attention as eco-friendly soil amendments that are more beneficial for plant growth, soil health, and remediation of contaminated soil. An experiment was performed in a paddy field to investigate the effects of two different types of BC (maize straw biochar and bamboo biochar) and AC (coconut shell activated carbon) in combination with rape organic fertilizer (R), calcium magnesium phosphate fertilizer (P), and fulvic acid (F), respectively, on soil Cd immobilization, Cd accumulation in rice, and yield. The results indicated that the BC/AC-based amendments reduced soil bioavailable Cd (DTPA-Cd) and brown rice Cd by 9.58%–27.06% and 19.30%–71.77%, respectively. The transformation of exchangeable Cd (Ex-Cd) to carbonate-bound Cd (Ca-Cd), Fe-Mn oxide bond (Ox-Cd), and residual (Re-Cd) in soil accounted for the mitigation of Cd uptake and enrichment by rice. Additionally, BC-/AC-based amendments altered soil physicochemical properties, which significantly increased the soil pH and cation exchange capacity (CEC), total nitrogen (TN), total phosphorus (TP), soil organic carbon (SOC), and dissolved organic carbon (DOC), directly promoting soil health. All BC-/AC-based amendments significantly increased FeIMP and MnIMP concentrations by 47.31%–160.34% and 25.72%–73.09% in the Fe/Mn plaque (IMP), respectively. Maize straw and bamboo biochar-based amendments significantly increased rice yield by 10.46%–20.41% and 9.94%–16.17%, respectively, while coconut shell-activated carbon severely reduced rice yield by 65.06%–77.14%. The correlation analysis revealed that leaf Cd and IMP primarily controlled Cd uptake by rice, and soil pH, Eh, CEC, SOC, IMP, and TP influenced DTPA-Cd in soil. This field study demonstrated that maize straw and bamboo biochar-based amendments not only reduced soil DTPA-Cd in paddy fields but also decreased the accumulation of Cd in brown rice, as well as improved rice yield, which has potential application in Cd-contaminated agriculture fields. Coconut shell-activated carbon severely decreased rice yields, which is not appropriate for rice production.
Modulating effects of temperature on CO2-inhibited isoprene emissions in Eucalyptus urophylla
Authors: Pang Weihua , Zhang Yanli , Zeng Jianqiang , Tian Xiao , Wang Xinming
Published: October 2024

Terrestrial vegetation emits substantial amounts of highly reactive isoprene, significantly impacting atmospheric chemistry and climate change. Both atmospheric carbon dioxide (CO2) concentration and temperature can influence plant isoprene emissions; however, whether these factors have a synergistic effect remains unclear, particularly for tropical/subtropical plants. In this study, we conducted in-situ controlled experiments on Eucalyptus urophylla, a representative tropical/subtropical species, to investigate the seasonal variation in the response of isoprene emissions to CO2 concentrations (ISOP-CO2 response) and to identify potential controlling factors. The results showed that high CO2 exerts a nearly linear inhibitory effect on isoprene emissions, as indicated by the slope of the ISOP-CO2 response curve. This inhibitory effect exhibited evident seasonal changes, with stronger suppression during cooler seasons and weaker suppression during warmer seasons. This finding contrasts with the default ISOP-CO2 response in the MEGAN model, which ignored seasonal variation. Further analysis showed a significant correlation between the slope of the ISOP-CO2 response curve and growth temperature from the past 10 days, indicating that these metrics are effective indicators for predicting seasonal changes. Our findings reveal a synergistic mechanism between temperature and CO2 concentration effects on isoprene emissions. By coupling the effects of growth temperature with the ISOP-CO2 response, this mechanism can be integrated into models to provide more accurate predictions of future isoprene emissions, reducing prediction biases, especially during cooler seasons.
Molecular diagnosis of patients with syndromic short stature identified by trio whole-exome sequencing
Authors: Sun Huihui , Zhang Geng , Li Na , Bu Xiangfang
Published: October 2024

Background

Short stature is a complex disorder with phenotypic and genetic heterogeneity. This study aimed to investigate clinical phenotypes and molecular basis of a cohort of patients with short stature.

Methods

Trio whole-exome sequencing (Trio-WES) was performed to explore the genetic aetiology and obtain a molecular diagnosis in twenty Chinese probands with syndromic and isolated short stature.

Results

Of the twenty probands, six (6/20, 30%) patients with syndromic short stature obtained a molecular diagnosis. One novel COMP pathogenic variant c.1359delC, p.N453fs*62 and one LZTR1 likely pathogenic variant c.509G>A, p.R170Q were identified in a patient with short stature and skeletal dysplasia. One novel de novo NAA15 pathogenic variant c.63T>G, p.Y21X and one novel de novo KMT2A pathogenic variant c.3516T>A, p.N1172K was identified in two probands with short stature, intellectual disability and abnormal behaviours, respectively. One patient with short stature, cataract, and muscle weakness had a de novo POLG pathogenic variant c.2863 T>C, p.Y955H. One PHEX pathogenic variant c.1104G>A, p.W368X was identified in a patient with short stature and rickets. Maternal uniparental disomy 7 (mUPD7) was pathogenic in a patient with pre and postnatal growth retardation, wide forehead, triangular face, micrognathia and clinodactyly. Thirteen patients with isolated short stature had negative results.

Conclusion

Trio-WES is an important strategy for identifying genetic variants and UPD in patients with syndromic short stature, in which dual genetic variants are existent in some individuals. It is important to differentiate between syndromic and isolated short stature. Genetic testing has a high yield for syndromic patients but low for isolated patients.
The indispensability of methyltransferase-like 3 in the immune system: from maintaining homeostasis to driving function
Authors: Zhang Mingfu , Gou Zhixian , Qu Yi , Su Xiaojuan
Published: October 2024

Methyltransferase-like 3(METTL3), recognized as the primary N6-methyladenosine methyltransferase, influences cellular functions such as proliferation, migration, invasion, differentiation, and fate determination by regulating gene expression post-transcriptionally. Recent studies have highlighted the indispensability of METTL3 in various immune cells such as hematopoietic stem/progenitor cells, innate immune cells (monocytes, macrophages, dendritic cells), and adaptive immune cells (thymic epithelial cell, T cells, natural killer cells). However, a comprehensive summary and analysis of these findings to elucidate the relationship between METTL3 and the immune system is yet to be undertaken. Therefore, in this review, we systematically collate reports detailing the mechanism underlying the role of METTL3 in regulating various immune processes and examine the modification of METTL3 and its potential implications. This review suggests that METTL3 plays an essential role in the immune system, ranging from maintaining homeostasis to regulating functions. Collectively, this review provides a comprehensive analysis of the relationship between METTL3 and the immune system, serving convenient researchers to understand the frontiers of immunological research and facilitate future clinical applications.
Spermidine attenuates chondrocyte inflammation and cellular pyroptosis through the AhR/NF-κB axis and the NLRP3/caspase-1/GSDMD pathway
Authors: Guo Xiaocheng , Feng Xinyuan , Yang Yue , Zhang He , Bai Lunhao
Published: October 2024

Introduction

Osteoarthritis (OA) is a prevalent chronic degenerative disease, marked by a complex interplay of mechanical stress, inflammation, and metabolic imbalances. Recent studies have highlighted the potential of spermidine (SPD), a naturally occurring polyamine known for its anti-inflammatory and antioxidant properties, as a promising therapeutic agent for OA. This study delves into the therapeutic efficacy and mechanistic pathways of SPD in mitigating OA symptoms.

Methods

Forty Sprague-Dawley rats were randomly assigned to four groups, including the CG (sham operation), model (anterior cruciate ligament transection [ACLT], and treatment (ACLT + two different doses of SPD) groups. In vivo, correlations between OA severity and different interventions were assessed by ELISA, X-rays, CT imaging, histological staining, and immunohistochemistry. In vitro, IL-1β was used to trigger chondrocyte inflammation, and SPD’s cytotoxicity was assessed in primary rat chondrocytes. Next, inflammatory markers, extracellular matrix (ECM) proteins, and pathway marker proteins were detected in chondrocytes administered IL-1β alone, SPD, or aryl hydrocarbon receptor (AhR) silencing, by qRT-PCR, Griess reaction, ELISA, Western blot, and immunofluorescence. Morphological alterations and pyroptosis in chondrocytes were examined by transmission electron microscopy (TEM) and flow cytometry.

Results

Our research reveals that SPD exerts significant anti-inflammatory and antipyroptotic effects on IL-1β-treated chondrocytes and in anterior cruciate ligament transection (ACLT) rat models of OA, primarily through interaction with the Aryl hydrocarbon receptor (AhR). Specifically, SPD’s binding to AhR plays a crucial role in modulating the inflammatory response and cellular pyroptosis by inhibiting both the AhR/NF-κB and NLRP3/caspase-1/GSDMD signaling pathways. Furthermore, the knockdown of AhR was found to negate the beneficial effects of SPD, underscoring the centrality of the AhR pathway in SPD’s action mechanism. Additionally, SPD was observed to promote the preservation of cartilage integrity and suppress ECM degradation, further supporting its potential as an effective intervention for OA.

Discussion

Collectively, our findings propose SPD as a novel therapeutic approach for OA treatment, targeting the AhR pathway to counteract the disease’s progression and highlighting the need for further clinical evaluation to fully establish its therapeutic utility.
Targeting the CSF1/CSF1R signaling pathway: an innovative strategy for ultrasound combined with macrophage exhaustion in pancreatic cancer therapy
Authors: Wang Qian , Wang Jianhong , Xu Ke , Luo Zhibin
Published: October 2024

Pancreatic cancer (PC) is a highly aggressive and lethal malignancy characterized by a complex tumor microenvironment (TME) and immunosuppressive features that limit the efficacy of existing treatments. This paper reviews the potential of combining ultrasound with macrophage exhaustion in the treatment of pancreatic cancer. Macrophages, particularly tumor-associated macrophages (TAMs), are crucial in pancreatic cancer progression and immune escape. Prolonged exposure to the immunosuppressive TME leads to macrophage exhaustion, reducing their anti-tumor ability and instead promoting tumor growth. The CSF1/CSF1R signaling pathway is key in macrophage recruitment and functional regulation, making it an effective target for combating macrophage exhaustion. Ultrasound technology not only plays a significant role in diagnosis and staging but also enhances therapeutic efficacy by guiding radiofrequency ablation (RFA) and percutaneous alcohol injection (PEI) in combination with immunomodulators. Additionally, ultrasound imaging can monitor the number and functional status of TAMs in real-time, providing a basis for optimizing treatment strategies. Future studies should further investigate the combined use of ultrasound and immunomodulators to refine treatment regimens, address challenges such as individual variability and long-term effects, and offer new hope for pancreatic cancer patients.
Clinical applications of STING agonists in cancer immunotherapy: current progress and future prospects
Authors: Wang Bin , Yu Wanpeng , Jiang Hongfei , Meng Xiangwei , Tang Dongmei , Liu Dan
Published: October 2024

The STING (Stimulator of Interferon Genes) pathway is pivotal in activating innate immunity, making it a promising target for cancer immunotherapy. STING agonists have shown potential in enhancing immune responses, particularly in tumors resistant to traditional therapies. This scholarly review examines the diverse categories of STING agonists, encompassing CDN analogues, non-CDN chemotypes, CDN-infused exosomes, engineered bacterial vectors, and hybrid structures of small molecules-nucleic acids. We highlight their mechanisms, clinical trial progress, and therapeutic outcomes. While these agents offer significant promise, challenges such as toxicity, tumor heterogeneity, and delivery methods remain obstacles to their broader clinical use. Ongoing research and innovation are essential to overcoming these hurdles. STING agonists could play a transformative role in cancer treatment, particularly for patients with hard-to-treat malignancies, by harnessing the body’s immune system to target and eliminate cancer cells.
Magnesium geochemistry of authigenic carbonate at marine cold seep
Authors: Tang Yukai , Lu Hailong , Yang Hailin
Published: October 2024

Cold seeps, featured by their extremely methane-rich sedimentary environments, play a significant role in the geological history and are common in marine sediments across the seafloor. Primary dolomite, possibly mediated by microorganisms, can be widely discovered in methane-rich environments. Hence, cold seeps may provide new insights into the ‘dolomite problem’, which has confused geologists for decades. Magnesium isotope geochemistry of seep carbonates contributes to the understanding of the dolomite formation mechanism in marine environments. In this paper, magnesium geochemical characteristics of carbonates in modern sediments are summarized, along with rare researches on magnesium isotopes of seep carbonates. Methane vigorously interacts with sulfate by anaerobic oxidation of methane at cold seeps, producing vast amounts of dissolved sulfide which can significantly promote dolomitization of seep carbonates. Compared with temperature, alkalinity, mineralogy, etc., the competition between rapid carbonate precipitation rates and aqueous ligands may be the main factor of the magnesium fractionation at cold seeps, which is controlled by the kinetic effect. The range of magnesium isotopes of seep carbonates is narrow (from -3.46‰ to -2.36‰), and an upper limit of magnesium content seems to exist. This characteristic may be a good indicator for identifying dolomitization related to anaerobic oxidation of methane. Whereas, mechanisms of magnesium isotope fractionation and dolomitization at cold seeps remain unclear, necessitating more natural samples tested, stimulated calculation and laboratory experiment.
Study on increasing load capacity of wooden arch bridge by CFRP strengthening: experimental and numerical Verification
Authors: Li Liping , Wang Yan , Zhang Yafei , Wang Xu , Ji Guangyao , Li Xuping
Published: October 2024

The wooden arch corridor bridge is a typical representative of Chinese wooden bridges, holding significant historical research value. Currently, these bridges face issues of severe component deformation and insufficient load-bearing capacity. To address these problems, this study employs CFRP reinforcement on the components of wooden arch corridor bridges to reduce deformation and enhance load-bearing capacity. Experimental research on CFRP reinforcement has yielded the elastic modulus of the bonding interface. Given the lack of an accurate numerical model for wooden arch corridor bridges, this study establishes a precise numerical model by setting parameters based on load test data from wooden arch corridor bridges. The elastic modulus obtained from the experiments is input into the numerical model for analysis. The results indicate that CFRP exhibits excellent reinforcement performance, with the load-bearing capacity of the reinforced damaged components still reaching 75%–85% of their original capacity, while the load-bearing capacity of the reinforced undamaged components increases to 130%–140% of their original capacity. The failure modes of the CFRP-reinforced wooden components suggest that allowing for some gaps in the bonding of CFRP can enhance overall ductility. The application of CFRP to wooden arch corridor bridges also demonstrates favorable reinforcement effects, increasing the load-bearing capacity of the arch surface by approximately 20%, thereby providing a theoretical basis for the reinforcement of wooden arch bridge frameworks.
Genome characterization of Shewanella algae in Hainan Province, China
Authors: Wang Licheng , Chen Shaojin , Xing Mei , Dong Lingzhi , Zhu Huaxiong , Lin Yujin , Li Jinyi , Sun Tuo , Zhu Xiong , Wang Xiaoxia
Published: October 2024

Shewanella algae is an emerging marine zoonotic pathogen. In this study, we first reported the Shewanella algae infections in patients and animals in Hainan Province, China. Currently, there is still relatively little known about the whole-genome characteristics of Shewanella algae in most tropical regions, including in southern China. Here, we sequenced the 62 Shewanella algae strains isolated from Hainan Province and combined with the whole genomes sequences of 144 Shewanella algae genomes from public databases to analyze genomic features. Phylogenetic analysis revealed that Shewanella algae is widely distributed in the marine environments of both temperate and tropical countries, exhibiting close phylogenetic relationships with genomes isolated from patients, animals, and plants. Thereby confirming that exposure to marine environments is a risk factor for Shewanella algae infections. Average nucleotide identity analysis indicated that the clonally identical genomes could be isolated from patients with different sample types at different times. Pan-genome analysis identified a total of 21,909 genes, including 1,563 core genes, 8,292 strain-specific genes, and 12,054 accessory genes. Multiple putative virulence-associated genes were identified, encompassing 14 categories and 16 subcategories, with 171 distinct virulence factors. Three different plasmid replicon types were detected in 33 genomes. Eleven classes of antibiotic resistance genes and 352 integrons were identified. Antimicrobial susceptibility testing revealed a high resistance rate to imipenem and colistin among the strains studied, with 5 strains exhibiting multidrug resistance. However, they were all sensitive to amikacin, minocycline, and tigecycline. Our findings clarify the genomic characteristics and population structure of Shewanella algae in Hainan Province. The results offer insights into the genetic basis of pathogenicity in Shewanella algae and enhance our understanding of its global phylogeography.
How the arts heal: a review of the neural mechanisms behind the therapeutic effects of creative arts on mental and physical health
Authors: Barnett Kelly Sarah , Vasiu Fabian
Published: October 2024

Background

The creative arts have long been known for their therapeutic potential. These modalities, which include dance, painting, and music, among others, appear to be effective in enhancing emotional expression and alleviating adverse physiological and psychological effects. Engagement in creative arts can be pursued as a personal hobby, in a classroom setting, or through a formal therapeutic intervention with a qualified therapist. Engagement can be active (i.e., creating) or passive (i.e., viewing, listening). Regardless of the modality and manner of engagement, the mechanisms explaining the therapeutic efficacy of creative arts remain poorly understood.

Objective

This study aims to systematically review research investigating the neurological mechanisms activated during active or passive engagement in creative arts, with a specific emphasis on the roles of the medial prefrontal cortex (mPFC) and the amygdala in emotional regulation (ER) and creative behaviors. The review seeks to provide preliminary evidence for the possible existence of common neural mechanisms underlying both phenomena, which could inform the development of targeted therapeutic interventions leveraging creative arts for ER.

Methods

A systematic review was conducted following the Cochrane Collaboration guideline and PRISMA standards to identify studies examining the neurological mechanisms underlying creative activities.

Results

A total of six out of 85 records meet the inclusion criteria, with all being basic research studies. Preliminary findings suggest that active and passive engagement with creative arts consistently activate neural circuits implicated in adaptive emotional regulation, including the mPFC and amygdala. These activations mirror the neural pathways engaged in effective ER strategies, suggesting the possible existence of shared mechanisms between creative expression and emotional processing.

Conclusion

The evidence underscores the potential of creative arts as a complementary therapeutic strategy alongside conventional care and other evidence-based mind-body modalities. By elucidating the shared neural mechanisms between creative arts engagement and ER, this review contributes to the theoretical and practical understanding of the role of creative arts in mental health. Future research is recommended to further explore these neural correlations and their implications for therapeutic practice.
Intrafamilial neurological phenotypic variability due to either biallelic or monoallelic pathogenic variants in CACNA1A
Authors: Mammadova Dilbar , Kraus Cornelia , Leis Thomas , Popp Bernt , Zweier Christiane , Reis Andre , Trollmann Regina
Published: October 2024

Pathogenic heterozygous variants in CACNA1A are associated with familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6, and more recently, neurodevelopmental disorders. We describe a severe, early-onset phenotype including severe muscular hypotonia, early-onset epileptic seizures, apnoea, optic atrophy and dysphagia in three siblings carrying compound heterozygous frameshift variants in CACNA1A. Two male patients died at the age of 5 or 14 months of suspected SIDS or severe developmental epileptic encephalopathy (DEE) with refractory seizures and apnoea. A male child (index patient) developed severe early-onset DEE including seizures and ictal apnoea at the age of 4 weeks. Another male child developed generalized epilepsy and mild intellectual impairment in late infancy, and his mother and his maternal uncle were identified as carriers of a known CACNA1A pathogenic variant [c.2602delG heterozygous, p. (Ala868Profs*24)] with a diagnosis of episodic ataxia type 2. This maternal pathogenic variant c.2602delG was detected in the index patient and child 2. Trio-Exome sequencing identified an additional heterozygous pathogenic variant in the CACNA1A gene, c.5476delC, p.(His1826Thrfs*30) in the index patient and child 2, which was inherited from the asymptomatic father. In conclusion, the novel compound heterozygosity for two frameshift pathogenic variants, maternally [c.2602delG, p.(Ala868Profs*24)] and paternally [c.5476delC, p.(His1826Thrfs*3)] is associated with a severe phenotype of early-onset DEE. This observation highlights the necessity of additional analyses to clarify unusual phenotypes even if a pathogenic variant has already been identified, and expands the clinical spectrum of CACNA1A-related disorders.