bluuebunny/crossref_metadata_2025 huggingface dataset:
Edukasi Faktor Risiko Kecacingan Dan Perilaku Hidup Bersih dan Sehat (PHBS) di Sekolah Pesisir Jambula
Authors: Armaijn Liasari , Darmayanti Dewi , Nurhidayat Rochmat , Tamsil Fauziah Auliah
Published: November 2024

Infeksi cacing yang ditularkan melalui tanah (Soil Transmitted Helminthiases/STH) diperkirakan telah menginfeksi 1,5 milyar orang (24%) dari populasi penduduk dunia. Penularan terjadi akibat kotoran manusia yang mencemari tanah pada daerah dengan sanitasi yang buruk. Anak sekolah dasar merupakan kelompok yang paling berisiko menderita kecacingan karena faktor anak tidak mencuci tangan sebelum makan dan sesudah Buang Air Besar (BAB), kebersihan kuku, jajan sembarangan dan perilaku BAB Sembarangan (BABS). Kecacingan dapat mengganggu kecerdasan dan gizi anak sehingga menjadi salah satu penyebab stunting atau gangguan pertumbuhan anak. Salah satu upaya pencegahan adalah melalui edukasi tentang faktor-faktor penyebab kecacingan dan Perilaku Hidup Bersih dan Sehat (PHBS) pada siswa sekolah dasar. Tujuan dari kegiatan ini adalah untuk meningkatkan pengetahuan dan derajat kesehatan pada siswa sekolah dasar di pesisir Jambula, sehingga membantu menurunkan angka kesakitan dan mencegah terjadinya kecacingan pada siswa anak sekolah dasar. Metode pengabdian ini dilakukan dengan edukasi dan simulasi PHBS pada 39 orang siswa SDN 65 Jambula. Setelah kegiatan pengabdian ini didapatkan peningkatan pengetahuan pada 31 orang sehingga disimpulkan bahwa masih dibutuhkan peningkatan pengetahuan guna mencegah perkembangan kecacingan.
Khitanan Massal sebagai Upaya Pencegahan Penyakit Infeksi pada Masyarakat Pesisir Jailolo
Authors: Nachrawi Tuthanurany , Toka Wahyunita Do , Rizky Hadiputra Narendra Agung , Yusuf Wahda
Published: November 2024

Program pengbadian kepada masyarakat ini bertujuan untuk memberikan pelayanan sirkumsisi kepda masyarakat di Kecamatan Jailolo, Halmahera Barat, Provinsi Maluku Utara. Kegiatan ini dilaksanakan pada 9-10 Mei 2024 serta melibatkan 86 peserta. Proses kegiatan dimulai dari publikasi melalui media sosial untuk menjaring peserta. Selanjutnya, persiapan dilakukan dengan berkoordinasi bersama pemerintah daerah dan Puskesmas Jailolo serta memastikan ketersediaan alat dan obat-obatan yang diperlukan. Pada hari pelaksanaan, peserta mendaftar di meja registrasi, diikuti dengan anamnesis dan pemeriksaan fisik. Sirkumsisi dilakukan dengan prosedur yang memenuhi standar kebersihan dan keamanan disertai edukasi mengenai perawatan luka kepada orang tua atau wali. Setelah tindakan, pasien diberikan obat-obatan berupa antibiotik dan anti-inflamasi, serta dipantau selama 30 menit untuk mengantisipasi perdarahan. Pemantauan lanjutan dilakukan hingga 48 jam pasca tindakan, kemudian diteruskan oleh Puskesmas Jailolo untuk perawatan lanjutan. Kegiatan ini bertujuan untuk meningkatkan kesehatan masyarakat dengan menyediakan akses sirkumsisi yang aman dan berkualitas, serta meningkatkan kesadaran akan pentingnya menjaga kebersihan organ genitalia.
Madencilik Faaliyetlerinde Halkın Katılımı: Sürdürülebilir Kalkınma Ve Kanada Maden Hukuku Perspektifi
Authors: Üstün Gül
Published: November 2024

Madencilik, ekonomik kalkınmaya önemli katkılar sağlarken, çevresel etkileri ve yerel
toplulukları nasıl etkilediği konularında endişelere neden olmaktadır. Bu bağlamda,
sürdürülebilir kalkınmanın sağlanması için madencilik faaliyetlerinin doğru bir şekilde
yönetilmesi gerekmektedir. Halkın katılımı, madencilik faaliyetlerinin düzenlenmesinde
demokratik değerlere dayalı bir zemin oluşturabilir. Yerel toplulukların madencilik
projelerine dahil olması, endişelerini paylaşmalarına olanak tanıyarak çözümlere katkı sağlar.
Bu katılımın sağlanması sürdürülebilir kalkınma hedeflerinin sağlanmasına ve maden
faaliyetinin sürdürülebilirliğinin sağlanmasına yardımcı olacaktır.
Madencilik sektöründe önemli bir yere sahip Kanada uygulamasında, çevresel etki
değerlendirmesi haricinde katılım ilkesi dikkate alınmakta olup, özellikle Britanya
Kolombiyası Yüksek Mahkemesinin 2023 yılında tesis ettiği karar bu konuda referans
alınacak niteliktedir.
O perspectivă asupra municipalităților și orașelor digitale și verzi
Authors: Drăgoi Andreea Emanuela , Dumitrescu George Cornel
Published: November 2024

Publicația este concepută ca o bază de cunoștințe interdisciplinară care cuprinde fundamentele, temele comune și provocările relevante pentru politica locală, digitalizarea la nivelul comunelor și orașelor și temele transformării verzi. Principalele grupuri țintă ale acestei publicații sunt cadrele didactice și cercetătorii, studenții universităților în administrație publică, științe politice și domenii conexe, precum și profesioniștii deja activi în organismele de autoguvernare ale comunelor sau orașelor. Experți din diverse universități și instituții de cercetare contribuie, prin intermediul acestei publicații, la îmbogățirea discuțiilor științifice, abordând probleme urgente și relevante legate de transformarea digitală și verde, cu un accent pe nivelul de guvernare comunal.
Postage Stamps Commemorating Afghanistan's Independence Day, 1920–2019: An Analysis and Interpretation
Authors: Kłagisz Mateusz M.P.
Published: November 2024

This article focuses on the description and analysis of postage stamps printed in Afghanistan to commemorate the anniversary of Independence Day. The study covers a period of one hundred years, from 1920 to 2019. Presented chronologically, the analysis identifies various symbols that are connected to the idea of independence and examines the relationships between these symbols and the dynamics of changes on the domestic political scene. The findings suggest a deliberate decision-making process in the selection of symbols, driven by specific ideological and political objectives, although the question regarding the factual influence of the stamp-oriented policy still needs to be researched. The article concludes with statistical data on the frequency of use of individual symbols and provides several examples of the postage stamps analyzed here.
The Impact of Political and Cultural Alterations on Crown Designs in the Herat School Paintings of the Timurid Period
Authors: Saravani Fahimeh , Mohammadi Zekrollah , Sarhaddi-Dadian Hossein
Published: November 2024

A crown or headwear was considered one of the most important parts of clothing in the past. More than any other article of clothing, it expressed one’s social position and status. As a symbol of royalty in Iran, the design of crowns evolved over different historical periods. At times, it was used as a symbol to show power and authority. At others, it was as a symbol of the tyranny of mighty kings, and sometimes a symbol of luxury and aristocratic life. The Timurid period, with all of its political and social turbulence, is considered one of the most brilliant periods of painting, where new details and subjects appeared. This article investigates the role of crowns and headdresses with a historical descriptive method based on the existing library sources. It shows how the design of the crown in the paintings of the Timurid period was mostly influenced by cultural and religious factors. Timurid artists of the Herat school did not stick to the historical facts. Instead they sought to present an ideal image of the king, following the standards of the era, displaying slight differences in each period and reign.
The effect of working fluid and compressibility on the optimal solidity of axial turbine cascades
Authors: Tosto Francesco , Colonna Piero , Pini Matteo
Published: November 2024

The blade solidity, namely the blade chord-to-pitch ratio, largely affects the fluid-dynamic performance of turbomachinery and its cost. For turbo-machines operating with air or steam, the optimal value of the solidity which maximizes the efficiency is estimated with empirical correlations such as the ones proposed by Zweifel (1945) and Traupel (1966). However, if the turbomachine operates with unconventional fluids, the accuracy of these correlations is questionable. Examples of such fluids are the organic compounds (e.g., hydrocarbons, siloxanes) used in organic Rankine cycle (ORC) power systems. This study concerns an investigation on how the working fluid, its thermodynamic state, and flow compressibility influence the optimum pitch-to-chord ratio of turbine stages. A first principle reduced-order model (ROM) for the computation of profile losses was developed for this purpose. The ROM results are compared with those obtained from numerical simulations of the flow over two axial turbine cascade geometries. The influence of both the working fluid, the flow compressibility, and the solidity value on both the boundary layer state at the blade trailing edge and the base pressure are evaluated. Models to compute mixing and passage losses in the compressible regime as a function of the axial solidity are proposed and discussed. Results show that the value of the optimal solidity of turbine cascades significantly increases with the flow compressibility, and mildly increases if the fluid is in the dense vapor state. Moreover, the optimal solidity value is strongly affected by the mixing process occurring downstream of the blade trailing edge. Therefore, currently available models for its estimation, which are solely based on the minimization of the profile losses, are inaccurate.
Approaches to reforming the simplified taxation system under the conditions of implementation of the National Revenue Strategy until 2030
Authors:   West Ukrainian National University, Krysovatyy Andriy , Valihura Volodymyr ,   West Ukrainian National University
Published: November 2024

Introduction. Subjects of small and medium-sized enterprises in global fiscal practice can be taxed either under the general tax system or through simplified tax regimes. The application of such taxation regimes is determined by a number of their advantages and is established at certain stages of the socio-economic development of the state. Problem Statement. In the conditions of Ukraine's European integration and a critical shortage of financial resources, there is an urgent need to reform the simplified taxation system in Ukraine. The National Revenue Strategy until 2030 (hereinafter - the Strategy) outlines the reasons and main directions of reform. Its main objective, in this regard, is to establish incentives for business entities to transition from a simplified to a general taxation system. Purpose.To substantiate the approaches to the development and operation of a simplified taxation system, and to form proposals for its design in Ukraine in line with the implementation of the Strategy. Methods. The research employed a variety of general scientific and specialized methods, including logical analysis, synthesis, induction and deduction, description, theoretical generalization, abstract-logical reasoning, critical analysis, comparison, and expert evaluation. Results. Based on the analysis of the negative and positive aspects of the operation of the simplified taxation system in Ukraine, the expediency of its preservation with the elimination of negative aspects and taking into account the needs of the socio-economic development of the state is substantiated. Key areas and approaches to the design of a simplified taxation system in Ukraine are determined. Proposals have been made to define individual elements of the simplified system in the context of the implementation of the Strategy. Conclusions. The study of the methodological foundations of the design of certain spheres of simplified taxation regimes reveals the existence of several alternatives in the selection of approaches to their formation. These approaches are influenced by the macroeconomic situation in the state and the choice of tasks to be achieved when introducing or reforming the simplified regime. The authors outlined proposals for the design of a simplified taxation system in Ukraine, highlighting key areas and evaluating the extent to which these proposals are reflected in the Strategy.
Methodological approaches to research and formation of institutional support for climate financing
Authors:   SESE “The Academy of Financial Management”, Shcherbakova Olena
Published: November 2024

Introduction. At the core of any scientific research lies the process of cognition, which necessitates clarification of the conceptual approach in accordance with the chosen methodology. The desired outcomes are determined not only by the initial theoretical stance of the researcher but also by a well-founded formulation of the problem and a specification of the directions for scientific inquiry. Thus, proper scientific cognition and the selection of specific general and special methods require an adequate theoretical and practical understanding of reality, necessitating a sophisticated methodology for scientific research. Problem Statement. Preventing, countering, and adapting to the negative impacts of climate change for the socio-economic development of countries and the deterioration of the environment require the establishment of effective institutional support for climate financing, aimed at mitigating these issues. To implement such measures through climate financing, a well-grounded methodology is essential for both research and the formation of institutional support for climate financial flows. Purpose. To define methodological approaches to the study and formation of institutional support for climate financing. Methods. A systemic approach was applied, along with monographic, historical, economic-statistical methods, and methods of comparative and expert analysis. Results. The significance of the methodology of scientific cognition has been established. Methodological approaches to the study and formation of institutional support for climate financing have been outlined, along with their components and the methodological arsenal for addressing the identified issues. Conclusions. To conduct a comprehensive study and establish institutional support for climate financing, advanced methodological approaches are required. These will enable a thorough understanding of the essence, varieties, functions, components, and instruments of such financing, facilitating the development of adequate institutional support to enhance the effectiveness of prevention, counteraction, and mitigation of the negative impacts of climate change and adaptation to these changes.
Critical and diverse role of alarmin cytokines in parasitic infections
Authors: Xing Zhou , Liu Suiyi , He Xing
Published: November 2024

Alarmin cytokines including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) function as danger signals to trigger host immunity in response to tissue injury caused by pathogenic factors such as parasitic infections. Parasitic diseases also provide an excellent context to study their functions and mechanisms. Numerous studies have indicated that alarmin cytokine released by non-immune cells such as epithelial and stromal cells induce the hosts to initiate a type 2 immunity that drives parasite expulsion but also host pathology such as tissue injury and fibrosis. By contrast, alarmin cytokines especially IL-33 derived from immune cells such as dendritic cells may elicit an immuno-suppressive milieu that promotes host tolerance to parasites. Additionally, the role of alarmin cytokines in parasite infections is reported to depend on species of parasites, cellular source of alarmin cytokines, and immune microenvironment, all of which is relevant to the parasitic sites or organs. This narrative review aims to provide information on the crucial and diverse role of alarmin cytokines in parasitic infections involved in different organs including intestine, lung, liver and brain.
Association of oxidative balance score with hyperuricemia and gout: NHANES 2009-2018
Authors: He Yiting , Chen Xiaojing , Ma Zeming , Wang Jingsa , Lin Kun
Published: November 2024

Introduction

Oxidative stress plays a crucial role in the development and progression of hyperuricemia/gout. This study aims to explore the relationship between the Oxidative Balance Score (OBS) and hyperuricemia/gout.

Methods

The study utilized complete data from adult participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2009 to 2018. OBS, composed of scores for 20 dietary and lifestyle factors, served as the exposure variable. Multivariable linear regression model was applied to evaluate the association between OBS and uric acid (UA). Multivariable logistic regression, subgroup analyses, and restricted cubic spline (RCS) regression were conducted to explore the relationship between OBS and hyperuricemia/gout.

Results

A total of 18,998 participants were included. In the fully adjusted model, compared to the lowest quartile, the highest quartiles of OBS, dietary OBS, and lifestyle OBS were negatively correlated with UA (β=-0.31 (-0.36,-0.25), β=-0.18 (-0.24,-0.12), and β=-0.64 (-0.69,-0.59), respectively) and hyperuricemia (OR=0.63 (0.55,0.71), OR=0.76 (0.67,0.86), OR=0.37 (0.33,0.42), respectively). Moreover, the highest quartiles of OBS and lifestyle OBS exhibited a negative correlation with gout (OR=0.72(0.58,0.91), OR=0.54 (0.43,0.67), respectively). Subgroup analyses revealed differences in the negative association between OBS and hyperuricemia concerning hypertension (p for interaction =0.002) and diabetes (p for interaction= 0.004), while gender-related disparities were observed in the negative association between OBS and gout (p for interaction =0.008). RCS analysis demonstrated a linear negative association between hyperuricemia and OBS (p for non-linearity >0.05), while gout exhibited a non-linear negative association (p for non-linearity<0.05).

Conclusion

The study found that a higher OBS was associated with a decreased risk of developing hyperuricemia/gout, underscoring its potential in the prevention and management of these conditions.
The combination of metformin and high glucose increased longevity of Caenorhabditis elegans a DAF-16/FOXO-independent manner: cancer/diabetic model via C. elegans
Authors: Berk Şeyda , Cetin Ali , Özdemir Özgür Ülkü , Pektaş Ayşe Nur , Yurtcu Nazan , Dastan Sevgi Durna
Published: November 2024

Introduction

Sedentary lifestyles and diets with high glycemic indexes are considered to be contributing factors to the development of obesity, type 2 diabetes in humans. Metformin, a biguanide medication commonly used to treat type 2 diabetes, has been observed to be associated with longevity; however, the molecular mechanisms underlying this observation are still unknown.

Methods

The effects of metformin and high glucose, which have important roles in aging-related disease such as diabetes and cancer, were studied in lin-35 worms because they are associated with cancer-associated pRb function in mammals and have a tumour suppressor property.

Results and Discussion

According to our results, the negative effect of high glucose on egg production of lin-35 worms was greater than that of N2 worms. High glucose shortened lifespan and increased body length and width in individuals of both strains. Metformin treatment alone extended the lifespan of N2 and lin-35 worms by reducing fertilization efficiency. However, when metformin was administered in the presence of high glucose, the lifespan of lin-35 worms was clearly longer compared to N2 worms. Additionally, we conclude that glucose and metformin in lin35 worms can extend life expectancy through a DAF-16/FOXO-independent mechanism. Furthermore, the results of this study will provide a new perspective on extending mammalian lifespan through the model organism C. elegans.
Identification of novel markers for neuroblastoma immunoclustering using machine learning
Authors: Zhang Longguo , Li Huixin , Sun Fangyan , Wu Qiuping , Jin Leigang , Xu Aimin , Chen Jiarui , Yang Ranyao
Published: November 2024

Background

Due to the unique heterogeneity of neuroblastoma, its treatment and prognosis are closely related to the biological behavior of the tumor. However, the effect of the tumor immune microenvironment on neuroblastoma needs to be investigated, and there is a lack of biomarkers to reflect the condition of the tumor immune microenvironment.

Methods

The GEO Database was used to download transcriptome data (both training dataset and test dataset) on neuroblastoma. Immunity scores were calculated for each sample using ssGSEA, and hierarchical clustering was used to categorize the samples into high and low immunity groups. Subsequently, the differences in clinicopathological characteristics and treatment between the different groups were examined. Three machine learning algorithms (LASSO, SVM-RFE, and Random Forest) were used to screen biomarkers and synthesize their function in neuroblastoma.

Results

In the training set, there were 362 samples in the immunity_L group and 136 samples in the immunity_H group, with differences in age, MYCN status, etc. Additionally, the tumor microenvironment can also affect the therapeutic response of neuroblastoma. Six characteristic genes (BATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM) were identified by machine learning, and these genes are associated with multiple immune-related pathways and immune cells in neuroblastoma.

Conclusions

BATF, CXCR3, GIMAP5, GPR18, ISG20, and IGHM may serve as biomarkers that reflect the conditions of the immune microenvironment of neuroblastoma and hold promise in guiding neuroblastoma treatment.
A comprehensive review of immune checkpoint inhibitor-related diabetes mellitus: incidence, clinical features, management, and prognosis
Authors: Zhou Lin , Yang Shuhui , Li Youtao , Xue Cheng , Wan Renping
Published: November 2024

Immune checkpoint inhibitor-related diabetes mellitus (ICI-DM) is a rare complication that medical oncologists seldom encounter in routine practice. The sporadic nature and intrinsic complexity of ICI-DM make it challenging to analyze comprehensively in experimental settings. In this review, we examine phase 3 clinical trials on ICIs and published case reports of ICI-DM, aiming to summarize its incidence, clinical features, management, and prognosis. Phase 3 clinical trials reveal that the incidence of ICI-DM is higher with combination therapies, such as anti-PD-1 and anti-CTLA-4 or anti-PD-L1, compared to anti-PD-1 monotherapy. ICI-DM typically presents as severe hyperglycemia with a fulminant onset and is often associated with diabetic ketoacidosis, accompanied by unexpectedly low HbA1c and C-peptide levels. ICI-DM shares similarities with classic type 1 diabetes, particularly in terms of autoimmunity and genetic predisposition. This includes a high prevalence of islet autoantibodies and susceptibility to certain HLA haplotypes, often with concurrent endocrine gland dysfunction. This suggests that genetic susceptibility and exposure to ICIs may both be necessary for triggering islet autoimmunity and inducing ICI-DM. Notably, patients with positive islet autoantibodies, such as glutamic acid decarboxylase antibody and islet-associated antigen 2 antibody, tend to experience rapid onset of ICI-DM after ICI exposure. Although patients with ICI-DM generally show a high objective response rate to immunotherapy, a significant proportion also face the need to permanently discontinued treatment. Further research is urgently needed to determine whether permanent discontinuation of immunotherapy is necessary and whether this discontinuation negatively impacts overall survival.
Prognostic value of EMT-related genes and immune cell infiltration in thyroid carcinoma
Authors: Wu Shuping , Liu Yu , Zeng Yu , Ruan Xianhui , Tao Mei , Lin Wenrong , Liu Chang , Chen Hongbin , Liu Hui , Wu Yu
Published: November 2024

Background

The Epithelial–Mesenchymal Transition (EMT) is a very important process involved in cancer invasion and metastasis. Additionally, the Cathepsin K (CTSK) gene is closely related to the degradation of the extracellular matrix, which is a critical component of the EMT. The purpose of this study was to determine the relationships between EMT-related genes and immune cell infiltration and their prognostic value in Thyroid carcinoma (THCA). The effect of the CTSK gene on the aggressive biological features of THCA was assessed.

Methods

Within the framework of the present study, the THCA cohort was analyzed in detail based on data obtained from The TCGA database in the context of the EMT. The TCGA-THCA cohort was then divided into two groups, namely, high- and low-risk groups, based on the calculated EMT scores. Finally, based on the findings from the Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm, LASSO regression analysis, and Kaplan−Meier plotter, we selected five genes (CTSK, C3ORF80, FBLN2, PRELP and SRPX2) associated with patient prognosis. Furthermore, this study examined the presence of various immune cells within the THCA samples using three distinct algorithms, namely ssGSEA, xCell, and MCPcounter. Additional studies have been conducted to establish the roles of CTSK in THCA cell proliferation and migration using various assays, such as CCK8, colony formation, EdU proliferation, Transwell migration and wound healing assays. Additionally, the involvement of CTSK in the regulation of various EMT-related markers was confirmed using Western blot analysis.

Results

Based on EMT scores, TCGA-THCA patients were further divided into two groups, and the study revealed that patients in the high-risk group had a worse prognosis than those in the low-risk group. Among the five genes linked to the prognostic value of EMT (CTSK, C3ORF80, FBLN2, PRELP, and SRPX2), CTSK exhibited notably elevated expression in the high-risk cohort. This group also exhibited pronounced immune cell infiltration, with a marked correlation observed between CTSK expression and the levels of macrophages, MDSCs, and various T-cell subtypes. Furthermore, in vitro studies demonstrated that reducing CTSK expression led to significant reductions in THCA cell viability; clonogenic, proliferative, motility and migratory capacities; and the expression of key EMT-related proteins, including N-cadherin, vimentin, slug, and snail.

Conclusion

Our results suggest that the expression of CTSK, a gene associated with the EMT, may be associated with THCA onset and progression and thus may serve as a promising prognostic biomarker.
Probiotics in piglet: from gut health to pathogen defense mechanisms
Authors: Jiang Zipeng , Yang Mingzhi , Su Weifa , Mei Liang , Li Yuqi , Guo Yuguang , Li Yangyuan , Liang Weifan , Yang Bo , Huang Zhiyi , Wang Yizhen
Published: November 2024

Various problems and obstacles are encountered during pig farming, especially the weaning phase when switching from liquid to solid feed. Infection by pathogenic bacteria causes damage to the intestinal barrier function of piglets, disrupts the balance of the intestinal microbiota, and destroys the chemical, mechanical, and immune barriers of the intestinal tract, which is one of the main causes of gut inflammation or gut diseases in piglets. The traditional method is to add antibiotics to piglet diets to prevent bacterial infections. However, long-term overuse of antibiotics leads to bacterial resistance and residues in animal products, threatening human health and causing gut microbiota dysbiosis. In this context, finding alternatives to antibiotics to maintain pre- and post-weaning gut health in piglets and prevent pathogenic bacterial infections becomes a real emergency. The utilization of probiotics in piglet nutrition has emerged as a pivotal strategy to promote gut health and defend against pathogenic infections, offering a sustainable alternative to traditional antibiotic usage. This review introduces recent findings that underscore the multifaceted roles of probiotics in enhancing piglet welfare, from fortifying the gut barrier to mitigating the impacts of common bacterial pathogens. Meanwhile, this study introduces the functions of probiotics from different perspectives: positive effects of probiotics on piglet gut health, protecting piglets against pathogen infection, and the mechanisms of probiotics in preventing pathogenic bacteria.
Gut microbiome and metabolomics in systemic sclerosis: feature, link and mechanisms
Authors: Yao Qicen , Tan Wenfeng , Bai Feihu
Published: November 2024

Systemic sclerosis (SSc) is a rare and highly heterogeneous chronic autoimmune disease characterized by multi-organ and tissue fibrosis, often accompanied by a poor prognosis and high mortality rates. The primary pathogenic mechanisms of SSc are considered to involve tissue fibrosis, autoimmune dysfunction, and microvascular abnormalities. Recent studies have shed light on the gut microbiota (GM) and metabolites in SSc patients, revealing their association with gastrointestinal symptoms and disease phenotypes. However, further elucidation is needed on the specific mechanisms underlying the interactions between GM, metabolites, and the immune system and their roles in the pathogenesis of SSc. This review outlines the characteristics of GM and metabolites in SSc patients, exploring their interrelationships and analyzing their correlations with the clinical phenotypes of SSc. The findings indicate that while the α-diversity of GM in SSc patients resembles that of healthy individuals, notable differences exist in the β-diversity and the abundance of specific bacterial genera, which are closely linked to gastrointestinal symptoms. Moreover, alterations in the levels of amino acids and lipid metabolites in SSc patients are prominently observed and significantly associated with clinical phenotypes. Furthermore, this review delves into the potential immunopathological mechanisms of GM and metabolites in SSc, emphasizing the critical role of interactions between GM, metabolites, and the immune system in comprehending the immunopathological processes of SSc. These insights may offer new scientific evidence for the development of future treatment strategies.
Mechanisms of autophagy and their implications in dermatological disorders
Authors: Xue Shenghao , Lin Yumeng , Chen Haoran , Yang Zhengyu , Zha Junting , Jiang Xuan , Han Zhongyu , Wang Ke
Published: November 2024

Autophagy is a highly conserved cellular self-digestive process that underlies the maintenance of cellular homeostasis. Autophagy is classified into three types: macrophage, chaperone-mediated autophagy (CMA) and microphagy, which maintain cellular homeostasis through different mechanisms. Altered autophagy regulation affects the progression of various skin diseases, including psoriasis (PA), systemic lupus erythematosus (SLE), vitiligo, atopic dermatitis (AD), alopecia areata (AA) and systemic sclerosis (SSc). In this review, we review the existing literature focusing on three mechanisms of autophagy, namely macrophage, chaperone-mediated autophagy and microphagy, as well as the roles of autophagy in the above six dermatological disorders in order to aid in further studies in the future.
A dual-purpose humanized mouse model for testing antiviral strategies against both SIV and HIV
Authors: Barnett Ella , Kaginkar Snehal , Schmitt Kimberly , Remling-Mulder Leila , Akkina Ramesh
Published: November 2024

Nonhuman primate (NHP) models employing simian/simian-human immunodeficiency viruses (SIV/SHIVs) played a major role in the study of HIV pathogenesis, latency, and cure studies in a preclinical setting. However, it took many years to arrive at the current effective triple drug ARV regimen against SIV due to the genetic differences with that of HIVs. Since new combinations of drugs will be used in the evolving HIV cure studies, a small animal model would be ideal to determine their efficacy against the commonly used SIVs such as SIVmac239 to triage ineffective drugs prior to their application in NHPs. We recently determined that humanized mice (hu-mice) with a transplanted human immune system are permissive to SIVmac strains in addition to HIVs. Based on this novel finding, here we evaluated the utility of this dual-purpose hu-mouse model to test different ART regimens against SIVmac239. Infected mice showing chronic viremia were treated with a combination anti-retroviral treatment (cART) regimen consisting of emtricitabine/elvitegravir/tenofovir disoproxil fumarate (FTC/EVG/TDF). Full viral suppression was seen for several weeks in SIVmac239-infected and treated mice similar to that seen with HIV-1 BaL virus used as a control. However, viral rebound was eventually observed in SIVmac239 infected mice during the treatment period, suggesting viral escape compared to HIV-1 BaL with which viral suppression was fully sustained. Next, a cART regimen consisting of emtricitabine/bictegravir/tenofovir alafenamide fumarate (FTC/BIC/TAF) was similarly evaluated. Our results showed that this ARV regimen was fully effective in rapidly suppressing both SIVmac239 and HIV-1 BaL. Complete viral suppression was maintained until treatment interruption after which viral loads rebounded. These findings highlight the utility of humanized mice for in vivo screening of new combinations of ARV compounds against various SIVs prior to employing them in NHPs. In addition to identifying new effective cART regimens against SIVs, this model would also be amenable to evaluating immunotherapeutic strategies using broadly neutralizing antibodies, LRAs and novel therapeutics in comparative cure studies of SIV and HIV.
Impact of submarine volcanic versus hydrothermal activity onto the strontium and lithium isotopic signatures of the water column (TONGA)
Authors: Chavagnac Valérie , Destrigneville Christine , Boulart Cédric , Taillandier Vincent , Vigier Nathalie , Guieu Cecile , Bonnet Sophie
Published: November 2024

During the TONGA cruise (2019), seawater samples were collected to assess the effect of volcanic eruption versus submarine hydrothermal system on the water column. For this purpose, two locations were investigated, the first one located directly under the influence of the New Late’iki island (eruption in October 2019), and the second one showing ongoing submarine hydrothermal activity. At both locations, the total strontium (TSr) and lithium (TLi) concentrations vary between 94.4 and 152.3 µmol/L and 13.2 and 203.5 µmol/L, respectively. When combined, TSr and TLi concentrations of all samples in the water column are higher than those of the oligotrophic water. Both volcanic eruption and submarine hydrothermal activity (e.g. volcanic ashes, particles, gas condensate) can deliver substantial amount of TSr and TLi to the water column. The distribution of TSr versus TLi evidences linear trends either with a negative or positive slope. The negative correlation is observed in the water column at both sites, directly under the influence of the eruption and in the vicinity of the volcano with hydrothermal activity. The positive TSr versus TLi correlation is observed at site under submarine hydrothermal influence and is in line with black smokers related hydrothermal plumes. The 87Sr/86Sr ratios vary between 0.709147 and 0.709210 and δ7Li values vary between +10.1 and +37.6 ‰. While 92% of the measured 87Sr/86Sr ratios are in line with the mean value of oligotrophic waters, once combined with the δ7Li values, only 20% of them remains within this field. The wide range of δ7Li values decreases from sea-surface down to ~140 mbsl, before increasing at greater depth, while defining different linear trend according to the dissolved inorganic carbon concentrations. The variability of δ7Li values reflect hydrothermal contribution, mineral–seawater interaction and potentially biology–environment interaction. In the particular geological setting of the study, where both hydrothermal and volcanic activities were at play, disentangling both contributions on water column implies a combined use of elemental and isotopic signatures of Sr and Li tracers.
Distinct responses of diatom- and flagellate-dominated Antarctic phytoplankton communities to altered iron and light supply
Authors: Camoying Marianne , Koch Florian , Stimpfle Jasmin , Pausch Franziska , Hassler Christel , Trimborn Scarlett
Published: November 2024

Primary production in the Southern Ocean is strongly influenced by the availability of light and iron (Fe). To examine the response of two distinct natural Antarctic phytoplankton communities (diatom vs. flagellates) to increasing light and Fe availability, we conducted two shipboard incubation experiments during late summer and exposed each community to increasing light intensities (30, 80, and 150 µmol photons m−2 s−1) with or without Fe amendment. Our results show clearly that both communities were Fe-limited since Fe addition resulted in higher particulate organic carbon (POC) production rates. The magnitude of the Fe-dependent increase in POC production, however, varied between the two stations being higher in the diatom-dominated community relative to the flagellate-dominated community. This differential response to increasing Fe supply could be attributed to the higher Fe requirement of the flagellate-dominated assemblage relative to the diatom-dominated assemblage. Irrespective of Fe availability, light also strongly stimulated the POC production of both communities between low and medium light supply (30 versus 80 µmol photons m−2 s−1), indicating that both assemblages were light-limited in situ. However, since POC production of both communities did not increase further at the highest light intensity (150 µmol photons m−2 s−1) even under high Fe supply, this suggests that light supply was saturated or that other conditions must be fulfilled (e.g., availability of trace metals other than Fe) in order for the communities to benefit from the higher light and Fe conditions.
High frequency radar error classification and prediction based on K-means methods
Authors: Wang Zhaoyi , Drevillon Marie , De Mey-Frémaux Pierre , Remy Elisabeth , Ayoub Nadia , Wang Dakui , Levier Bruno
Published: November 2024

This study aims to characterize the high frequency radar and numerically simulated low-frequency filtered currents in the south-eastern Bay of Biscay (study area) using a K-means classification algorithm based on an improved Euclidean Distance calculation method that does not take missing values. The errors between observations and simulations was estimated and predicted based on this classification method. Results indicate that predominantly eastward (northward) currents over the Spanish (French) continental shelf/slope in winter and more variable currents in the west and south-west in summer. The model classification results for circulation characteristics are in relatively good agreement with HF radar results, especially for currents on the Spanish (French) shelf/slope. In addition, the probabilistic relationship between observed and modeled currents was explored, obtaining the probability of occurrence of modeled current groups when each group of observed currents occurs. Finally, predictions of model and observed current errors were made based on the classification results, and it was found that the predictions based on the classification of all data had the smallest errors, with a 17% improvement over the unclassified control experiment. This study provides a foundation for subsequent model error testing, forecast product improvement and data assimilation.
Application of metabolomics approach to investigate the flavor substance differences between triploid and diploid oysters (Crassostrea angulata)
Authors: Chen Duo , Zheng Zewen , Zhou Ziquan , Song Yuxin , Chen Zhi , Lin Gang , Xue Ting
Published: November 2024

Oysters, particularly Portuguese oyster (Crassostrea angulata), are highly valued for their nutritional and flavor qualities, making them important in global aquaculture. Triploid oysters have gained attention for maintaining higher meat quality year-round compared to diploids, but there is limited research on how ploidy affects their biochemical and flavor profiles. This study uses a non-targeted metabolomics approach, including gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), to investigate flavor substance differences between triploid and diploid C. angulata. A total of 13 volatile compounds were identified in diploid oysters, while 28 were found in triploids. Significant upregulation of inosine, guanosine, L-aspartic acid, and taurine in triploids contributes to their enhanced flavor profile. Additionally, triploids showed higher nicotinamide concentrations, while diploids had increased 25-hydroxycholesterol. These findings highlight the advantages of triploid oysters in aquaculture for improved flavor and nutrition, supporting their potential for year-round production.
Development and evaluation of ibuprofen-loaded chitosan nanoparticles for pulmonary therapy
Authors: Olvera Rodríguez I. , Mora-Muñoz J. M. , Pérez V. , Campos-Guillén J. , Gallegos-Reyes M. A. , García-Solís P. , Álvarez López A. , Vallejo Becerra V. , Rodríguez-Morales J. A. , Rodríguez-Méndez A. J. , Guzmán Martínez C.
Published: November 2024

Lung injuries are increasingly prevalent due to various diseases causing alveolar damage, potentially leading to respiratory disorders. This study employed an incubation method to develop nano-encapsulated ibuprofen within a chitosan matrix for targeted pulmonary therapy. The encapsulation was successful without altering the molecular structure of chitosan, and a 500 mg dose was identified as optimal through lung tissue cell viability and histological analysis. The controlled release mechanism of this formulation ensures targeted delivery to the lungs, reducing inflammation and promoting alveolar regeneration. This approach highlights the importance of dose optimization and presents a promising strategy to enhance the efficacy and safety of pulmonary treatments.
Total baseline tumor size predicts survival among patients with advanced small-cell lung cancer receiving chemotherapy plus programmed death-ligand 1 inhibitor as first-line therapy: a multicenter retrospective observational study
Authors: Tanaka Anna , Teranishi Shuhei , Kajita Yukihito , Hirose Tomofumi , Kaneko Ayami , Sairenji Yu , Kawashima Hidetoshi , Yumoto Kentaro , Tsukahara Toshinori , Miura Kenji , Kobayashi Nobuaki , Yamamoto Masaki , Nishihira Ryuichi , Kudo Makoto , Miyazawa Naoki , Nishikawa Masanori , Kaneko Takeshi
Published: November 2024

Introduction

Total baseline tumor size (BTS) is a prognostic factor for programmed death 1 and programmed death-ligand 1 (PD-L1) inhibitor treatments. However, the prognostic value of total BTS for patients with small-cell lung cancer (SCLC) who receive chemotherapy plus PD-L1 inhibitor remains unknown. Thus, in this study, we aimed to determine whether total BTS is associated with prognosis in patients with SCLC who receive chemotherapy plus PD-L1 inhibitor as first-line therapy.

Methods

This study included patients with extensive-stage SCLC or post-chemoradiotherapy recurrence of limited-stage SCLC who received chemotherapy plus PD-L1 inhibitor as first-line therapy from August 2019 to December 2022. The two lesions with the largest diameter among the measurable lesions in each organ were selected from up to five organs (maximum of 10 lesions), and the sum of all diameters was defined as total BTS. The patients were divided into two groups, large or small, with total BTS using X-tile software. Median survival was analyzed using the Kaplan–Meier method, and the groups were compared using the log-rank test. Univariate and multivariate analyses examined the association between total BTS and prognosis.

Results

Fifty patients were included; 14% had large total BTS (>183.2 mm) and 86% had small total BTS (≤183.2 mm). The median observation period was 10.5 months. The large total BTS group showed significantly worse overall survival than the small total BTS group (median: 26.8 months vs. 5.7 months, P = 0.0003). The multivariate analysis indicated that large total BTS was an independent negative predictor of overall survival (hazard ratio: 7.14, 95% confidence interval: 1.89–26.96).

Discussion

Total BTS is a potentially useful prognostic factor for patients with advanced SCLC who receive chemotherapy plus PD-L1 inhibitor as first-line therapy.
Multidisciplinary Canadian consensus on the multimodal management of high-risk and radioactive iodine-refractory thyroid carcinoma
Authors: Ezzat Shereen , Pasternak Jesse D. , Rajaraman Murali , Abdel-Rahman Omar , Boucher Andrée , Chau Nicole G. , Chen Shirley , Gill Sabrina , Hyrcza Martin D. , Lamond Nathan , Massicotte Marie-Hélène , Winquist Eric , Mete Ozgur
Published: November 2024

Most follicular cell-derived differentiated thyroid carcinomas are regarded as low-risk neoplasms prompting conservative therapeutic management. Here, we provide consensus recommendations reached by a multidisciplinary group of endocrinologists, medical oncologists, pathologists, radiation oncology specialists, a surgeon and a medication reimbursement specialist, addressing more challenging forms of this malignancy, focused on radioactive iodine (RAI)-resistant or -refractory differentiated thyroid carcinoma (RAIRTC). In this document we highlight clinical, radiographic, and molecular features providing the basis for these management plans. We distinguish differentiated thyroid cancers associated with more aggressive behavior from thyroid cancers manifesting as poorly differentiated and/or anaplastic carcinomas. Treatment algorithms based on risk-benefit assessments of different multimodal therapy approaches are also discussed. Given the scarcity of data supporting management of this rare yet aggressive disease entity, these consensus recommendations provide much needed guidance for multidisciplinary teams to optimally manage RAIRTC.
The causal nexus between diverse smoking statuses, potential therapeutic targets, and NSCLC: insights from Mendelian randomization and mediation analysis
Authors: Cao Zhenghua , Zhao Shengkun , Wu Tong , Ding Huan , Tian Zhiyu , Sun Feng , Feng Zhuo , Hu Shaodan , Shi Li
Published: November 2024

Objective

Lung cancer, the most prevalent malignancy, is typically diagnosed at an advanced stage. Smoking is a pivotal risk factor for NSCLC, yet the impact of various smoking statuses on NSCLC remains unclear. Thus, this study aims to explore whether different smoking statuses can causally influence NSCLC through effects on predictive targets, offering a novel perspective for NSCLC treatment.

Methods

Employing dual-sample MR, MVMR, and TSMR approaches, we assessed the causal relationships between 13 distinct smoking statuses and NSCLC, using predicted potential therapeutic targets as mediators to further elucidate the causal interplay among them.

Results

Among the 13 smoking statuses, current tobacco smoking, exposure to tobacco smoke outside the home, past tobacco smoking, and never smoked demonstrated causal relationships with NSCLC. MVMR analysis reveals that Current tobacco smoking is an independent risk factor for NSCLC. Utilizing NCAPD2, IL11RA, and MLC1 as mediators, IL11RA (22.2%) was found to potentially mediate the relationship between past tobacco smoking and NSCLC.

Conclusion

This study, integrating bioinformatics and MR analysis, identified three potential predictive targets as mediators to investigate the causal relationships between different smoking statuses and NSCLC through potential therapeutic targets, providing new insights for the treatment and prevention of NSCLC.