bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling human social security during war
Authors: Bazhenova Olena , Varnalii Zakharii , Cheberyako Oksana , Mykytiuk Oksana
Published: October 2024

This paper explores the impact of economic and social policy on the life expectancy at birth as it determines the human social security in the country, reflecting the level of life support, well-being, social protection and self-preservation, as well as the level of education and self-development. We identified a certain “trap of social insecurity”, when a low level of income in the country leads to the degradation of human capital, a decrease in life expectancy due to the lack of adequate social protection that may ultimately lead to the slowdown in economic development. This mechanism of maintaining social insecurity significantly accelerates during military conflicts. From the cluster analysis, we can conclude that hybrid wars do not have a noticeable effect on the average life expectancy of the population. The empirical results of the panel VAR model showed slight response of life expectancy to economic and social policy shocks in Armenia, Azerbaijan, Georgia, Moldova and Ukraine – countries that are the victims of either hybrid wars or full-scale hostilities on the territory of the former USSR. The most significant effect on life expectancy is exerted by the growth of gross domestic product per capita. Current health expenditure per capita shocks have a small positive effect on life expectancy in the short run. On the other hand, unemployment and the factor of hybrid wars and military conflicts have a slight negative impact in the short term. In the long run, all the above impacts are leveled off. At the same time, the results of decomposition of the variance of the forecast errors of life expectancy at birth showed that its volatility is largely explained by the inherent fluctuations of this indicator. The variation of gross domestic product per capita explains about 9% of the variation in life expectancy at birth in the selected countries, unemployment – slightly more than 2%.
Interval-valued intuitionistic fuzzy pattern recognition model for assessment of social cohesion
Authors: Imanov Gorkhmaz , Aliyev Asif
Published: October 2024

Social cohesion is defined as the potential of a society to sustain the well-being, eliminate inequality, ensure the rights for every citizen, respect for dignity, the opportunities for human development and realization, and engagement of all individuals in the democratic system. There exist numerous researches in this direction differing in the method, structure and number of indicators constituting Social Cohesion Index (SCI). In the present study, we developed an approach based on interval-valued intuitionistic fuzzy tools for the assessment of SCI. In the adoption of the structure of SCI, we relied on the UN methodology. The advantages of the proposed approach are in taking into account the uncertainty caused by crisp input data and classical computation techniques. The issues addressed in the research encompass the effect of indicators on the overall SCI, computation of the weights of indicators and sub-indices, producing the aggregated index and assessing its level through fuzzy pattern recognition tools. The approach proposed in the current work can be a substantial advance in the methodology of SCI calculations.
Optimizing Program Management in Healthcare: Leveraging AI And Data Science for Enhanced Decision-Making and Patient Outcomes
Authors:   Technical Program Manager, United States, Anand Royana
Published: October 2024

The healthcare industry is rapidly evolving with the integration of artificial intelligence (AI) and data science. This paper explores how these technologies can optimize program management in healthcare, enhancing decision-making processes and improving patient outcomes. We examine current challenges in healthcare program management, the role of AI and data science in addressing these challenges, and case studies that illustrate successful applications. Finally, we discuss future trends and provide recommendations for healthcare organizations seeking to leverage AI and data science effectively
Partition function approach to non-Gaussian likelihoods: macrocanonical partitions and replicating Markov-chains
Authors: Herzog Maximilian Philipp , von Campe Heinrich , Kuntz Rebecca Maria , Röver Lennart , Schäfer Björn Malte
Published: October 2024

Monte-Carlo techniques are standard numerical tools for exploring non-Gaussian and multivariate likelihoods. Many variants of the original Metropolis-Hastings algorithm have been proposed to increase the sampling efficiency. Motivated by Ensemble Monte Carlo we allow the number of Markov chains to vary by exchanging particles with a reservoir, controlled by a parameter analogous to a chemical potential μ, which effectively establishes a random process that samples microstates from a macrocanonical instead of a canonical ensemble. In this paper, we develop the theory of macrocanonical sampling for statistical inference on the basis of Bayesian macrocanonical partition functions, thereby bringing to light the relations between information-theoretical quantities and thermodynamic properties. Furthermore, we propose an algorithm for macrocanonical sampling, 𝙰𝚟𝚊𝚕𝚊𝚗𝚌𝚑𝚎 𝚂𝚊𝚖𝚙𝚕𝚒𝚗𝚐, and apply it to various toy problems as well as the likelihood on the cosmological parameters Ωm and w on the basis of data from the supernova distance redshift relation.
MAPEAMENTO GEOMORFOLÓGICO DA BACIA HIDROGRÁFICA DO RIACHO DO COITÉ - ITIÚBA-BA
Authors: Silva Emerson Santos da , Souza Sirius Oliveira
Published: October 2024

As bacias hidrográficas têm passado por alterações, sobretudo de origem antrópica, que rompem com a dinâmica de seus elementos hidrogeomorfológicas. Neste viés, a Cartografia Geomorfológica constitui uma das formas de análise dos ambientes naturais, incluindo as bacias hidrográficas, pois propicia possibilidades de representação do relevo. Deste modo, este trabalho tem por objetivo propor o mapeamento geomorfológico da bacia do riacho do Coité, município de Itiúba, Estado da Bahia (BA), no nordeste do Brasil, como ferramenta de auxílio ao uso e ocupação da terra, com base na metodologia proposta pelo IBGE (2009). A metodologia do trabalho consistiu na aquisição das fotografias aéreas e realização da estereoscopia digital, o georreferenciamento e a vetorização das feições do relevo, cuja integração dos dados foi realizada em ambiente de Sistema de Informação Geográfica (SIG) com uso do software QGIS (versão 3.10.14). No que tange aos resultados, identificou-se o predomínio de formas e processos atuantes relacionadas aos Modelados de Aplainamento, referente ao pedimento, Modelados de Dissecação, representado pelos relevos residuais da Serra de Itiúba, e Modelados de acumulação, referente as planícies aluviais. Esta pesquisa ressalta a importância do ordenamento territorial e conservação destes ambientes e de novos trabalhos que visem estudar o semiárido nordestino.
Tiếp cận giáo dục đại học và ảnh hưởng đến vốn con người ở Việt Nam
Authors: Nguyễn Đăng Núi
Published: October 2024

Bài viết phân tích tác động của tiếp cận giáo dục đại học đến chỉ số vốn con người tại Việt Nam. Sử dụng dữ liệu từ Khảo sát mức sống dân cư (VHLSS) của Tổng cục Thống kê, nghiên cứu khẳng định tiếp cận giáo dục đại học, thu nhập và sức khỏe có ảnh hưởng tích cực đến vốn con người, trong khi các yếu tố như dân tộc thiểu số và khu vực nông thôn có tác động tiêu cực. Mô hình hồi quy tuyến tính đa biến kết hợp với phương pháp thay thế lặp và Bootstrap được sử dụng để đảm bảo tính chính xác và đáng tin cậy của các ước lượng. Các khuyến nghị chính sách tập trung vào việc mở rộng cơ hội tiếp cận giáo dục đại học và cải thiện cơ sở hạ tầng dịch vụ công để đảm bảo phát triển đồng đều vốn con người.
Stay or Leave: Investigating Factors Impact Crowd-Based Workers’ Platform-Based Justice Perceptions and Turnover Intentions
Authors: Song Xiaochuan
Published: October 2024

Crowdsourcing has emerged as a transformative business model, harnessing collective intelligence to tackle complex tasks efficiently. However, the impact of crowd-based platforms on workers’ justice perceptions is still understudied. This research delves into organizational justice perceptions among crowd-based workers, focusing on platform features that influence these perceptions as well as workers’ subsequent turnover intentions. Drawing on data collected from 364 workers across multiple platforms, findings indicate that equitable compensation policies, participative evaluation, interactive and considerate communication, and rule-based evaluation can enhance procedural, distributive, and interactional justice perceptions, which in turn, significantly reduce turnover intentions. Moreover, media richness moderates part of these relationships, strengthening the mitigating effects of justice perceptions on turnover intentions. The study contributes to understanding the dynamics of organizational justice in crowdsourcing contexts and provides insights for platform management strategies to enhance worker retention.
Discretionary Accrual in the Knowledge-Based Economy
Authors: Hsu Pei-Hui , Jan Ching-Lih , Shima Kim
Published: October 2024

The modern economy transit from manufacturing to knowledge-based industries that are dependent on investments in R&D, advertising, and employee talents. These investments and much of the value that they generate cannot be capitalized as assets. As these intangible assets are off-balance-sheet, a firm’s book value might be low. When book value fails to present a firm’s true value, we stipulate that management has incentive to manage its earnings to convey information that is not reflected in the balance sheet. We find that firms with negative book value and in the New Economy use more discretionary accruals.
EVALUATING HIGHER EDUCATION WEBSITE QUALITY USING WEBQUAL 4.0 AND IMPORTANCE PERFORMANCE ANALYSIS (IPA)
Authors: Murdoko Wiji , Jatnika Ihsan
Published: October 2024

LLDikti Region III is a unit operating under the Ministry of Education, Culture, Research, and Technology, responsible for promoting the enhancement of higher education quality in Jakarta. One of the media used by LLDikti Region III to serve stakeholders is through its website; therefore, the quality of services on the website must be continuously enhanced. The aim of this research is to determine whether the LLDikti Region III website meets user expectations, measured using the Webqual 4.0 method and Importance-Performance Analysis (IPA). Usability, information quality, and service interaction quality that will be used to evaluate the quality of this website. The respondents consist of members of the academic community from universities within the LLDikti Region III. Data was collected through an online questionnaire using stratified sampling techniques with 165 respondents. The results of this study show that 54.9% of the website's quality affects user satisfaction, while the remainder is influenced by variables not tested in this study. Based on the analysis conducted using the IPA method, several indicators in quadrant I still require significant attention, as they are considered important by users but have low performance. From these findings, the researcher suggests developing the website in areas where performance is low, particularly for indicators in quadrant I.
Dialectics, Mathematics and the Cavaillès-Hyppolite Encounter
Authors: Nilsson Alice
Published: October 2024

This essay utilises Suzanne Bachelard's essay ‘Forme et Contenu’ as an entry point to sketch out the possibility (or impossibility) of a dialectic of mathemata following the work of Jean Cavaillès and Jean Hyppolite. Firstly, I outline what Bachelard sees as a ‘dialectic’ of form and content in the history of abstract algebra, highlighting a parallel between Bachelard's reading of algebra and Hyppolite reading of the relation of the human subject to logos. Secondly, I move towards Jean Hyppolite's discussion of Lautman in ‘Mathematical Thought’ which allows for a revealing of convergences between the work of Hyppolite and Cavaillès. I conclude by noting that the similarities between Cavaillès and Hyppolite – despite possible protestations by Hyppolite – go against Hegel's understanding of mathematics, leading to the possibility of opening up a ‘Hegelian mathematics against Hegel’.
Peningkatan Kemampuan Komunikasi Orang Tua-Anak pada Keluarga Penerima Manfaat Program Keluarga Harapan Kelurahan Banjarsari Kota Metro
Authors: Prihantika Ita , Pratama Moch. Johan , Aprilia Hani Damayanti , Utami Nurul
Published: October 2024

Pandemi Covid-19 tidak hanya berdampak pada kesehatan jasmani, namun juga kesehatan psikologis. Pandemi Covid-19, salah satunya berdampak pada berbagai pelanggaran terhadap hak-hak anak yang dilakukan oleh orang tua. Lurah Banjarsari mengungkapkan bahwa kegiatan anak-anak dalam pembelajaran daring belum optimal, terjadi salah asuh (kekerasan verbal) sehingga pemanfaatan waktu luang pada kegiatan yang tidak bermanfaat. Kegiatan PKM ini ditujukan secara khusus ditujukan untuk meningkatkan keterampilan utamanya para ibu dalam berkomunikasi dengan anak untuk menjaga kesehatan mental ibu dalam pola pengasuhan melalui pendekatan responsive dan positive parenting. Sasaran kegiatan ini yaitu keluarga penerima PKH yang akan menjadi agen perubahan di masyarakat. Hasilnya pengabdian ini: (1) terjadi perubahan secara kognitif yaitu terjadi peningkatan rata-rata sebesar 0,56 (normal); (2) kesediaan peserta pengabdian untuk membentuk komunitas peduli kesehatan mental pada kelompok Keluarga Penerima Manfaat PKH di Kelurahan Banjarsari.
Pengelolaan Sampah Berkelanjutan melalui Pendampingan Pembuatan Pupuk Kompos dari Sampah Rumah Tangga di Desa Cileles Kecamatan Jatinangor Kabupaten Sumedang
Authors: Nooraini Afni
Published: October 2024

Persoalan sampah masih menjadi pekerjaan rumah yang belum terselesaikan sampai saat ini di tiap daerah, termasuk di Desa Cileles Kabupaten Sumedang. Desa Cileles belum melakukan pengelolaan sampah organik secara optimal. Sehingga, penulis melakukan kegiatan Pengabdian kepada Masyarakat (PkM) di Desa Cileles terkait pendampingan pembuatan pupuk kompos dari sampah rumah tangga yaitu sampah organik kepada masyarakat di Desa Cileles. Tujuan dilakukan PkM ini adalah untuk meningkatkan edukasi masyarakat terkait pengelolaan sampah, masyarakat lebih mandiri dalam mengelola sampah rumah tangga, mengurangi volume sampah di TPA Cibeureum dan meningkatkan perekonomian masyarakat. Metode yang dilakukan dalam PkM ini yaitu sosialisasi dan praktikum secara langsung pembuatan pupuk kompos dari sampah rumah tangga. Hasil PkM adalah masyarakat memahami pengelolaan sampah secara berkelanjutan dan mampu membuat pupuk kompos dari sampah rumah tangganya sendiri.
Pendampingan Optimalisasi Penggunaan Aset untuk Kesejahteraan Masyarakat Desa di Wilayah Kecamatan Sungai Raya
Authors: Sumarno Dwi Agus , Nurhadi Nurhadi , Seran Silverius Tey
Published: October 2024

Tujuan kegiatan pengabdian ini adalah meningkatkan pengetahuan dan pengalaman pemerintah desa di Kecamatan Sungai Raya, Kabupaten Kubu Raya, supaya pemerintah desa dapat memanfaatkan potensi desa dengan lebih baik melalui pengelolaan aset desa untuk meningkatkan kesejahteraan masyarakat desa.. Untuk berikutnya, hasil pengoptimalan aset desa tersebut dapat dijadikan pertimbangan dalam pengembangan Kawasan perdesaan di wilayah Kecamatan Sungai Raya dengan memanfaatkan aset desa berupa sumber daya alam dan aset fisik lainnya, serta mendatangkan pendapatan bagi masyarakat. Kegiatan yang dilakukan berbentuk Forum Group Discussion (FGD), pelatihan dan serta dengan pendampingan dalam rangka Optimalisasi Aset Desa serta peningkatan kapasitas kelembagaan kelompok desa maupun masyarakat yakni: Perangkat Desa, Badan Usaha Milik Desa (Bumdesa), dan Masyarakat setempat. Peserta yang terlibat dalam kegiatan ini direncanakan berjumlah 20 orang yang merupakan perangkat desa di wilayah Kecamatan Sungai Raya, Kabupaten Kubu Raya. Metode yang digunakan dalam kegiatan ini di antaranya: kegiatan Ceramah dan tanya jawab tentang peraturan pengelolaan aset desa, Memberikan pelatihan teknis pengisian aplikasi pencatatan aset desa dalam bentuk Pemberdayaan, serta Pendampingan pengendalian aset desa. Secara khusus kegiatan pengabdian ini telah mengarah pada beberapa capaian tujuan di antaranya yakni: terbangunnya komitmen di antara aparatur desa dalam pengoptimalan pengelolaan aset desa di setiap desa Kecamatan Sungai Raya, di antaranya yakni (1) optimalisasi Sumber Daya Alam yang tersedia (SDA), (2) potensi hasil bumi, dan (3) pemanfaatan teknologi. Desa – desa di Kecamatan Sungai Raya belum optimal dalam pengelolaan suatu aset atau kekayaan milik desa untuk keberlangsungan desa. Untuk itu, kehadiran Tim PkM IPDN membantu dan mendampingi pemerintah desa dalam mengoptimalkan aset desa yang dimiliki.
FORMULASI SEDIAAN GEL EKSTRAK DAUN SUKUN (Artocarpus altilis) SEBAGAI TERAPI LUKA SAYAT PADA KELINCI NEW ZEALAND WHITE
Authors: Raharjo Danang , Ika Dwi Ningrum  , Listyani Tiara Ajeng
Published: October 2024

Breadfruit leaf (Artocarpus altilis) is a type of plant that has a single to oval leaf from the Moraceae family. There are secondary metabolites in breadfruit leaves (Artocarpus altilis), namely flavonoids, tannins, and saponins which are efficacious as a treatment for the wound healing process. This study aims to determine whether breadfruit leaf extract (Artocarpus altilis) can be formulated into a gel preparation and to determine the maximum concentration of breadfruit leaf extract (Artocarpus altilis) in wound healing. This study was an experimental study to determine the maximum concentration in healing cuts with varying concentrations of 6.25%, 12.5%, and 25% tested on 5 male rabbits with 3 treatment groups. Wound healing data were analyzed using One Way ANOVA (Analysis of Varian) and the physical evaluation of the gel preparation was analyzed descriptively. The results showed that breadfruit leaf extract (Artocarpus altilis) could be formulated into gel preparations and fulfilled the physical evaluation test for gel preparations. Statistical test results had a significant effect on wound healing in rabbits p=0.001 (p<0.05) and the maximum concentration in wound healing was a concentration of 25% with a healing time of 11 days.
Is social media causing the spike in mental ill-health, self-harm and suicidal ideation in young people and are age restrictions the answer?
Authors: Robinson Jo , La Sala Louise
Published: October 2024

This commentary piece explores the question ‘is social media causing the increase in mental ill-health, self-harm and suicidal ideation in young people and if so, age restrictions are the answer?’ Whilst there is no question that rates of mental ill-health, self-harm and suicidal ideation are increasing in young people, questions certainly remain regarding the role of social media and, in turn, whether blanket age restriction will help solve these problems. In this piece we draw on the findings from two Lancet Commissions which highlight that the factors contributing to mental ill-health, self-harm and suicide are complex and include a range of social determinants and individual factors, of which social media is likely only one [1,2]. We also note that the relationship between social media use and mental health, self-harm and suicide, is poorly understood, with most of the evidence correlational at best. Indeed, our own research identifies that in addition to the potential for harm social media can provide a range of benefits, including social connection and access to help and information, often in the absence of professional help [3]. When it comes to the question of age restrictions, there is no evidence to support blanket restrictions, and in fact the potential for unintended harmful consequences exists, leading us to conclude that if we really want to tackle the current youth mental health crisis, we need a much more comprehensive and evidence-based approach.
Development of nanocomposite hydrogel using citrate-containing amorphous calcium phosphate and gelatin methacrylate
Authors: Indurkar Abhishek , Rubenis Kristaps , Boccaccini Aldo R. , Locs Janis
Published: October 2024

Nanocomposite hydrogels are suitable in bone tissue engineering due to their resemblance with the extracellular matrix, ability to match complex geometries, and ability to provide a framework for cell attachment and proliferation. The nanocomposite hydrogel comprises organic and inorganic counterparts. Gelatin methacrylate (GELMA) is an extensively used organic biomaterial in tissue engineering due to its excellent biocompatibility, biodegradability, and bioactivity. The photo-crosslinking of GELMA presents a challenge when aiming to create thicker nanocomposite hydrogels due to opacity induced by fillers, which obstructs the penetration of ultraviolet (UV) light. Therefore, using a chemical crosslinking approach, we have developed nanocomposite GELMA hydrogel in this study by incorporating citrate-containing amorphous calcium phosphate (ACP_CIT). Ammonium persulfate (APS) and Tetramethylethylenediamine (TEMED) were deployed to crosslink the methacrylate group of GELMA. The oscillatory shear tests have confirmed that crosslinking enhances both storage (G′) and loss modulus (G″) of GELMA. Subsequently, incorporation of ACP_CIT in GELMA hydrogel shows further enhancement in G′ and G″ values. In vitro analysis of the developed hydrogels revealed that chemical crosslinking and incorporation of ACP_CIT do not compromise the cytocompatibility of the GELMA. Hence, for developing nanocomposite GELMA hydrogels employing APS/TEMED crosslinking emerges as a promising alternative to photo-crosslinking.
The induction of bone formation by 3D-printed PLGA microsphere scaffolds in a calvarial orthotopic mouse model: a pilot study
Authors: Klar Roland M. , Cox James C. , Houchen Claire J. , Raja Naren , Bouloussa Houssam , Lohfeld Stefan
Published: October 2024

Polymeric biodegradable microspheres are readily utilized to support targeted drug delivery for various diseases clinically. 3D printed tissue engineering scaffolds from polymer filaments with embedded microspheres or nanoparticles, as well as bulk microsphere scaffolds, have been investigated for regenerative medicine and tissue engineering. However, 3D printed scaffolds consisting only of a homogenous microsphere size with an optimized architecture that includes a unique micro- and macroporosity, have been challenging to produce and hence, have not been assessed in the literature yet. Utilizing our recently established 3D-MultiCompositional Microsphere-Adaptive Printing (3D-McMap) method, the present study evaluated the effectiveness of 3D-printed poly (lactic-co-glycolic acid) (PLGA) microsphere scaffolds, consisting of microsphere sizes 50, 100, or 200 μm, on the induction of bone formation when implanted in the calvarial murine regeneration model. Our results showed that PLGA microsphere scaffolds possess unique properties that support bone regeneration by supporting osteoconduction and stimulating, in our opinion, true spontaneous osteoinduction. The study demonstrated that PLGA microsphere-based scaffolds support bone growth in the absence of additional growth factors and promote osteogenesis primarily via their unique geometric configuration. The larger the microspheres were, the greater de novo bone formation was. This proves that bone tissue engineering scaffolds 3D printed from microspheres, enabled by the 3D-McMap method, are superior over bulk material printed scaffolds, as they possess the unique capability of spontaneous induction of new bone formation. With the addition of encapsulated modulatory bone-forming biomolecules they can substantially improve the spatiotemporal control of tissue morphogenesis, potentially leading to new innovative clinical tissue repair therapies that regenerate bone in large defects correctly and fully.
Harnessing the potential of deep eutectic solvents in biocatalysis: design strategies using CO2 to formate reduction as a case study
Authors: Logarušić Marijan , Šubar Karla , Nikolić Maja , Jurinjak Tušek Ana , Damjanović Anja , Radović Mia , Radojčić Redovniković Ivana , Žnidaršič-Plazl Polona , Kroutil Wolfgang , Cvjetko Bubalo Marina
Published: October 2024

Introduction

Deep eutectic solvents (DESs) have emerged as green solvents with versatile applications, demonstrating significant potential in biocatalysis. They often increase the solubility of poorly water-soluble substrates, serve as smart co-substrates, modulate enzyme stereoselectivity, and potentially improve enzyme activity and stability. Despite these advantages, screening for an optimal DES and determining the appropriate water content for a given biocatalytic reaction remains a complex and time-consuming process, posing a significant challenge.

Methods

This paper discusses the rational design of DES tailored to a given biocatalytic system through a combination of experimental screening and computational tools, guided by performance targets defined by solvent properties and process constraints. The efficacy of this approach is demonstrated by the reduction of CO2 to formate catalyzed by NADH-dependent formate dehydrogenase (FDH). By systematically analyzing FDH activity and stability, NADH stability (both long-term and short-term stability after solvent saturation with CO2), and CO2 solubility in initially selected glycerol-based DESs, we were able to skillfully guide the DES screening process.

Results and discussion

Considering trade-offs between experimentally determined performance metrics of DESs, 20% solution of choline chloride:glycerol in phosphate buffer (ChCl:Gly80%B) was identified as the most promising solvent system for a given reaction. Using ChCl:Gly as a co-solvent resulted in an almost 15-fold increase in FDH half-life compared to the reference buffer and stabilized the coenzyme after the addition of CO2. Moreover, the 20% addition of ChCl:Gly to the buffer improved the volumetric productivity of FDH-catalyzed CO2 reduction in a batch system compared to the reference buffer. The exceptional stability of the enzyme in this co-solvent system shows great potential for application in continuous operation, which can significantly improve process productivity. Additionally, based on easily measurable physicochemical solvent properties and molecular descriptors derived from COSMO-RS, QSAR models were developed, which successfully predicted enzyme activity and stability, as well as coenzyme stability in selected solvent systems with DESs.
Solid-phase electrochemiluminescence immunosensing platform based on bipolar nanochannel array film for sensitive detection of carbohydrate antigen 125
Authors: Lu Shaolong , Wu Jiayi , Luo Tao , Liu Junjie , Xi Fengna , Zhang Wenhao
Published: October 2024

Development of simple solid-phase electrochemiluminescence (ECL) immunosensor with convenient fabrication for high-performance detection of tumor biomarkers is crucial. Herein, a solid-phase ECL immunoassay was constructed based on a bipolar silica nanochannel film (bp-SNA) modified electrode for highly sensitive detection of carbohydrate antigen 125 (CA 125). Inexpensive and readily available indium tin oxide (ITO) electrode was used as the supporting electrode for the growth of bp-SNA. bp-SNA consists of a bilayer SNA film with different functional groups and charge properties, including negatively charged inner layer SNA (n-SNA) and positively charged outer layer SNA (p-SNA). The nanochannels of bp-SNA were used for the immobilization of ECL emitter tris(bipyridine)ruthenium(II), while the outer surface was utilized for constructing the immunorecognition interface. Due to the dual electrostatic interaction composed of electrostatic attraction from n-SNA and electrostatic repulsion from p-SNA, ECL emitter could be stably confined within bp-SNA, providing stable and high ECL signals to the modified electrode. After amino groups on the outer surface of bp-SNA were derivatized with aldehyde groups, recognition antibodies could be covalently immobilized, and an immunosensor was obtained after blocking nonspecific sites. When CA 125 binds to the antibodies on the recognition interface, the formed complex reduces the diffusion of the co-reactant tripropylamine (TPrA) to the supporting electrode, decreasing the ECL signal. Based on this mechanism, the constructed immunosensor can achieve sensitive ECL detection of CA 125. The linear detection range is from 0.01 to 100 U/mL, with a detection limit of 4.7 mU/mL. CA 125 detection in serum is also achieved. The construction immunosensor has advantages including simple and convenient fabrication, high stability of the immobilized emitter, and high selectivity, making it suitable for CA 125 detection.
An equation for estimating low-density lipoprotein-triglyceride content and its use for cardiovascular disease risk stratification
Authors: Wolska Anna , Sampson Maureen , Zubirán Rafael , Meeusen Jeff W. , Donato Leslie J. , Jaffe Allan S. , Remaley Alan T.
Published: October 2024

Background

The triglyceride (TG) content of low-density lipoprotein (LDL-TG) has been shown to be more predictive of atherosclerotic cardiovascular disease (ASCVD) events than the cholesterol content of LDL (LDL-C). The goal of our study was to develop an equation for estimating LDL-TG (eLDL-TG) based on the standard lipid panel and to compare it to estimated LDL-C as an ASCVD risk biomarker.

Methods

Using least-square regression analysis, the following eLDL-TG equation was developed: eLDL-TG=TG38.5+NonHDL-C5.75+9.75TGNonHDL-C+244HDL-C−2.95. LDL-TG was measured by the β-quantification (BQ) reference method (N = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and eLDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) (N = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) (N = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study (N = 14,632).

Results

eLDL-TG showed better ASCVD risk stratification of UKB participants than LDL-C (Wilcoxon Chi-Square: 2,099.6 vs. 418.7, respectively). Receiving-operating characteristics analysis revealed that eLDL-TG had a stronger association with ASCVD events than LDL-C (AUC: 0.596 vs. 0.542, respectively) and other conventional lipid markers. Similar findings were found in ARIC. Discordance analysis in UKB showed that the group with low LDL-C/high eLDL-TG had a similar risk as the high LDL-C/high eLDL-TG group. Furthermore, these same two groups with the highest eLDL-TG levels and the highest ASCVD event rate also had higher mean levels of systolic blood pressure, Body Mass Index, hemoglobin A1C, and C-reactive protein than the two lower eLDL-TG groups. Using eLDL-TG > 44.6 mg/dl (80th percentile) as a cut-point leads to a hazard ratio of 1.32 (95% CI, 1.29–1.36) for ASCVD events, which remained significant after adjustment for LDL-C and apoB. Furthemore, using eLDL-TG as a risk-enhancer test leads to reclassification of 50% more high-risk individuals than current lipid-enhancer test rules.

Conclusions

Like LDL-C, LDL-TG can also be calculated from the results of the standard lipid panel. Compared to estimated LDL-C, eLDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.
Recent advances in positron emission tomography for detecting early fibrosis after myocardial infarction
Authors: Wu Qiuyan , Song Jialin , Liu Wenyan , Li Li , Li Sijin
Published: October 2024

Cardiac remodeling after myocardial infarction is one of the key factors affecting patient prognosis. Myocardial fibrosis is an important pathological link of adverse ventricular remodeling after myocardial infarction, and early fibrosis is reversible. Timely detection and intervention can effectively prevent its progression to irreversible ventricular remodeling. Although imaging modalities such as CMR and echocardiography can identify fibrosis, their sensitivity and specificity are limited, and they cannot detect early fibrosis or its activity level. Positron emission tomography (PET) allows non-invasive visualization of cellular and subcellular processes and can monitor and quantify molecules and proteins in the fibrotic pathway. It is valuable in assessing the extent of early myocardial fibrosis progression, selecting appropriate treatments, evaluating response to therapy, and determining the prognosis. In this article, we present a brief overview of mechanisms underlying myocardial fibrosis following myocardial infarction and several routine imaging techniques currently available for assessing fibrosis. Then, we focus on the application of PET molecular imaging in detecting fibrosis after myocardial infarction.
Alternating carnivore and Neanderthal activities at Escoural Cave: insights from the taphonomic and machine learning analysis of leporid remains
Authors: Cobo-Sánchez Lucía , Rufà Anna , Cascalheira João
Published: October 2024

Exploring the varied subsistence strategies and cave occupation patterns of Neanderthals is key to understanding their complex behaviors and ecological adaptations. Small game consumption, in particular, is considered a relevant indicator of their behavioral complexity. Rabbit assemblages from Pleistocene cave sites provide valuable insights into Neanderthal interactions with small prey and potential competition with carnivores. Here, we present the first detailed taphonomic analysis of faunal remains from Escoural Cave (Portugal), where a European rabbit (Oryctolagus cuniculus) assemblage was found alongside Middle Paleolithic stone tools and some macromammal remains. This study combines traditional zooarchaeological and taphonomic analysis of the rabbit remains with multivariate statistics and machine learning methods to establish the origin of the accumulation, and the implications for Neanderthal subsistence and cave use. Results from the taphonomic analysis show no evidence of human consumption but abundant evidence of small terrestrial carnivore activity, primarily from lynxes. This could indicate a sequential occurrence of Neanderthal and carnivore activities in the cave, with Neanderthal activities likely related to something other than rabbit consumption. Our study contributes to characterizing Iberian carnivore fossil accumulations and differentiating between faunal assemblages accumulated by carnivores and those by hominins. Additionally, we show that the use of machine learning analysis provides a robust and objective method for identifying and classifying taphonomic signatures, enhancing the accuracy and reliability of our interpretations. Future work will focus on analyzing additional faunal collections from both past and new excavations at Escoural, to test whether carnivores and Neanderthals focused on different prey types and how they shared the cave space.
Field experiments and main understanding of shale oil hydraulic fracturing
Authors: Zhao Mengyun
Published: October 2024

To understand the key processes of hydraulic fracturing in shale oil reservoirs, such as artificial fracture initiation and extension, proppant transportation and settlement, and the influencing factors of post-fracture production, many hydraulic fracturing field tests have been conducted in the United States. Examples include the ConocoPhillips tests and the National Hydraulic Fracturing Experiment. The results have promoted the innovation and development of fracturing technology. A good correlation exists between lithological changes and the roughness of artificial fractures. Although numerous artificial cracks are created, the number that can provide oil and gas seepage is relatively small, determined by the effectiveness of these cracks. The settlement of proppants in actual geological formations involves factors such as geology, lithology, fractures, and stress. The pressure data indicate that when the reservoir pressure drops below the bubble point pressure, the decline in production sharply increases. The key variables affecting shale oil well production include the horizontal well position, well spacing, horizontal section length, and sand addition intensity. These technologies are suitable for the adaptive process of China’s terrestrial shale oil fracturing, promoting the development and rapid increase of shale oil production.
Dysregulation of the 3β-hydroxysteroid dehydrogenase type 2 enzyme and steroid hormone biosynthesis in chronic kidney disease
Authors: Zuo Yiyi , Zha Dongqing , Zhang Yue , Yang Wan , Jiang Jie , Wang Kangning , Zhang Runze , Chen Ziyi , He Qing
Published: October 2024

Introduction

Chronic kidney disease (CKD) presents a critical global health challenge, marked by the progressive decline of renal function. This study explores the role of the 3β-hydroxysteroid dehydrogenase type 2 enzyme (HSD3B2) and the steroid hormone biosynthesis pathway in CKD pathogenesis and progression.

Methods

Using an adenine-induced CKD mouse model, we conducted an untargeted metabolomic analysis of plasma samples to identify key metabolite alterations associated with CKD. Immunohistochemistry, Western blotting, and qPCR analyses were performed to confirm HSD3B2 expression in both human and mouse tissues. Additionally, Nephroseq and Human Protein Atlas data were utilized to assess the correlation between HSD3B2 and kidney function. Functional studies were conducted on HK2 cells with HSD3B2 knockdown to evaluate the impact on cell proliferation and apoptosis.

Results

Metabolic characteristics revealed significant shifts in CKD, with 61 metabolites increased and 65 metabolites decreased, highlighting the disruption in steroid hormone biosynthesis pathways influenced by HSD3B2. A detailed examination of seven key metabolites underscored the enzyme's central role. HSD3B2 exhibited a strong correlation with kidney function, supported by data from Nephroseq and the Human Protein Atlas. Immunohistochemistry, Western blotting, and qPCR analyses confirmed a drastic reduction in HSD3B2 expression in CKD-affected kidneys. Suppressed proliferation and increased apoptosis rates in HSD3B2 knocked down HK2 cells further demonstrated the enzyme's significance in regulating renal pathophysiology.

Discussion

These findings underscore the potential of HSD3B2 as a clinical diagnostic and therapeutic target in CKD. While further studies are warranted to fully elucidate the mechanisms, our results provide valuable insights into the intricate interplay between steroid hormone biosynthesis and CKD. This offers a promising avenue for precision medicine approaches and personalized treatment strategies.
Immunological characteristics of bronchoalveolar lavage fluid and blood across connective tissue disease-associated interstitial lung diseases
Authors: Hirano Aiko , Sakashita Aki , Fujii Wataru , Baßler Kevin , Tsuji Taisuke , Kadoya Masatoshi , Omoto Atsushi , Hiraoka Noriya , Imabayashi Tatsuya , Kaneko Yoshiko , Sofue Hideaki , Maehara Yosuke , Seno Takahiro , Wada Makoto , Kohno Masataka , Fukuda Wataru , Yamada Kei , Takayama Koichi , Kawahito Yutaka
Published: October 2024

Interstitial lung disease (ILD) is a serious complication of connective tissue diseases (CTDs). The heterogeneity of ILDs reflects differences in pathogenesis among diseases. This study aimed to clarify the characteristics of CTD-ILDs via a detailed analysis of the bronchoalveolar lavage fluid (BALF) and blood immune cells. BALF and blood samples were collected from 39 Japanese patients with newly diagnosed ILD: five patients with Sjögren’s syndrome (SS), eight patients with dermatomyositis (DM), six patients with rheumatoid arthritis (RA), six patients with systemic sclerosis, four patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, and 10 patients with idiopathic interstitial pneumonia. We performed single-cell RNA sequencing to analyze the gene expression profiles in these patients’ immune cells. In patients with SS, B cells in the BALF were increased and genes associated with the innate and acquired immunity were enriched in both the BALF and blood. In contrast, patients with DM showed an upregulation of genes associated with viral infection in both the BALF and blood. In patients with RA, neutrophils in the BALF tended to increase, and their gene expression patterns changed towards inflammation. These disease-specific characteristics may help us understand the pathogenesis for each disease and discover potential biomarkers.
Bayesian metamodeling of early T-cell antigen receptor signaling accounts for its nanoscale activation patterns
Authors: Neve-Oz Yair , Sherman Eilon , Raveh Barak
Published: October 2024

T cells respond swiftly, specifically, sensitively, and robustly to cognate antigens presented on the surface of antigen presenting cells. Existing microscopic models capture various aspects of early T-cell antigen receptor (TCR) signaling at the molecular level. However, none of these models account for the totality of the data, impeding our understanding of early T-cell activation. Here, we study early TCR signaling using Bayesian metamodeling, an approach for systematically integrating multiple partial models into a metamodel of a complex system. We inform the partial models using multiple published super-resolution microscopy datasets. Collectively, these datasets describe the spatiotemporal organization, activity, interactions, and dynamics of TCR, CD45 and Lck signaling molecules in the early-forming immune synapse, and the concurrent membrane alterations. The resulting metamodel accounts for a distinct nanoscale dynamic pattern that could not be accounted for by any of the partial models on their own: a ring of phosphorylated TCR molecules, enriched at the periphery of early T cell contacts and confined by a proximal ring of CD45 molecules. The metamodel suggests this pattern results from limited activity range for the Lck molecules, acting as signaling messengers between kinetically-segregated TCR and CD45 molecules. We assessed the potential effect of Lck activity range on TCR phosphorylation and robust T cell activation for various pMHC:TCR association strengths, in the specific setting of an initial contact. We also inspected the impact of localized Lck inhibition via Csk recruitment to pTCRs, and that of splicing isoforms of CD45 on kinetic segregation. Due to the inherent scalability and adaptability of integrating independent partial models via Bayesian metamodeling, this approach can elucidate additional aspects of cell signaling and decision making.
Single-cell RNA sequencing uncovers molecular mechanisms of intravenous immunoglobulin plus methylprednisolone in Kawasaki disease: attenuated monocyte-driven inflammation and improved NK cell cytotoxicity
Authors: Yang Minna , Chen Yeshi , Feng Chenhui , Zhang Mingming , Wang Hongmao , Zheng Yang , Li Xiaohui
Published: October 2024

Introduction

Intravenous immunoglobulin (IVIG) plus methylprednisolone as initial intensive therapy or additional therapy in Kawasaki disease (KD) has been used in clinical practice. However, its molecular and cellular mechanism is unclear.

Methods

We performed single-cell analysis on 14 peripheral blood mononuclear cell (PBMC) samples obtained from 7 KD patients who received either IVIG monotherapy or IVIG plus methylprednisolone therapy. This encompassed 4 samples from KD patients collected before and after IVIG treatment, as well as 3 samples from KD patients before and after IVIG plus methylprednisolone therapy.

Results

Both IVIG monotherapy and IVIG plus methylprednisolone therapy can increase lymphocyte counts (e.g. CD4+T, CD8+T, and gdT cells) to address lymphopenia. They can also decrease monocyte counts and repress the expression of S100A12, NLRP3, and genes associated with immune-cell migration in monocytes. IVIG combined with methylprednisolone downregulates more monocyte-driven inflammatory pathways than IVIG alone. Additionally, this combination uniquely enhances NK cell cytotoxicity by modulating receptor homeostasis, while significantly upregulating interferon-related genes in CD4+ T cells, CD8+ T cells, and B cells, particularly type I interferons.

Conclusion

The combination of IVIG with methylprednisolone attenuated monocyte-driven inflammation and improved NK cell cytotoxicity which might provide clues for pediatricians to consider treatment options for children with KD. Whether the monocyte-driven hyperinflammatory state and NK cell function can be indicators for the clinical choice of IVIG with methylprednisolone therapy in KD needs further investigation.
Daikenchuto, a Japanese herbal medicine, ameliorates experimental colitis in a murine model by inducing secretory leukocyte protease inhibitor and modulating the gut microbiota
Authors: Ozaka Sotaro , Sonoda Akira , Kudo Yoko , Ito Kanako , Kamiyama Naganori , Sachi Nozomi , Chalalai Thanyakorn , Kagoshima Yomei , Soga Yasuhiro , Ekronarongchai Supanuch , Ariki Shimpei , Mizukami Kazuhiro , Ishizawa Shiori , Nishiyama Mitsue , Murakami Kazunari , Takeda Kiyoshi , Kobayashi Takashi
Published: October 2024

Background

Inflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD.

Methods

Experimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs).

Results

Oral administration of DKT increased the number of butyrate-producing bacteria, such as Parabacteroides, Allobaculum, and Akkermansia, enhanced the levels of short-chain fatty acids, including butyrate, in the colon, induced SLPI expression, and ameliorated DSS-induced colitis in WT mice. We found that mouse colon carcinoma cell line treatment with either DKT or butyrate significantly enhanced the expression of SLPI. Moreover, supplementation of DKT protected the intestinal epithelial barrier with augmented expression of TJPs in WT mice, but not in KO mice. Finally, the composition of the gut microbiota was changed by DKT in WT mice, but not in KO mice, suggesting that DKT alters the colonic bacterial community in an SLPI-dependent manner.

Conclusion

These results indicate that DKT exerts anti-inflammatory effects on the intestinal epithelial barrier by SLPI induction, due, at least in part, to increased butyrate-producing bacteria and enhanced butyrate levels in the colon. These results provide insight into the mechanism of the therapeutic effects of DKT on IBD.