bluuebunny/crossref_metadata_2025 huggingface dataset:
Змінні шпиндельні головки обробних центрів із модернізованими сполучними елементами
Authors: Кроль О.С. , Цанков П.
Published: September 2024

Розглянуто процес 3D моделювання приводу головного руху обробного центру (ОЦ) зі змінними формоутворюючими шпиндельними головками та модифікованими зубчастими муфтами. Представлені тривимірні моделі формотворчих вузлів ОЦ, призначених для різних технологічних операцій методами свердління, фрезерування та розточування складних корпусних деталей. Показано ефективність використання нових функціоналів: граничного представлення геометрії B-rep та тривимірної операції «Вирізання», адаптованих для побудови 3D моделей корпусних деталей приводу та шпиндельних головок. Використано модуль розрахунків механічних передач Компас Gears, в якому реалізуються геометричне моделювання та розрахунки на міцність циліндричних і конічних зубчастих передач та зубчастих муфт в процесі 3D моделювання. Зазначено, що при застосуванні тривимірної операції побудови зубчастих вінців методом імітації зубофрезерування досягається підвищення швидкості профілювання робочих поверхонь зубчастого зачеплення. Висунуто ідею вдосконалення конструкції зубчастих муфт за критерієм мінімізації навантажувальної здатності, які використовуються для з’єднання валів приводу оброблювального центру з валами вертикальної, довбальної та кутової шпиндельними головками. Запропоновано заміну класичного циліндричного профілю робочої поверхні зуба внутрішнім конічним зачепленням зубів з круговим профілем. Зроблено аналітичний розрахунок основних геометричних характеристик модифікованого профілю зачеплення зубів зубчастих муфт. Введений коефіцієнт довжини зубів стосовно стандартної та модифікованої конструкцій, як критерій оцінки рівня згинальних напруг у зоні контакту. Обґрунтовано припущення, що отримані розрахункові значення коефіцієнта форми зуба для випадку евольвентного зачеплення мало відрізняються при розгляді кругового профілю модифікованої муфти в межах робочої висоти витка на ділильному діаметрі. Відзначено вплив коефіцієнта форми зубів на зниження рівня контактної напруги. Реалізовано експериментальний розрахунок комплексного коефіцієнта зниження напруги для модифікованої конструкції зубчастої муфти.
Consentimiento informado en práctica médica y en investigación clínica
Authors: Velastegui Hernández Rita Elizabeth , Tagua Moyolema Ana Elizabeth , Barrionuevo Torres Viviana Estefania , Sogso Chano Christian Vicente , Vargas Ortiz Bryan Nicolás , Velastegui Hernández Rommel Santiago
Published: September 2024

Introducción. El consentimiento informado es un pilar fundamental en la práctica médica y la investigación clínica, evolucionando de un modelo paternalista a uno que enfatiza la autonomía del paciente y la toma de decisiones compartida. A lo largo del tiempo, la importancia de garantizar que los pacientes y participantes en estudios clínicos comprendan plenamente los procedimientos, riesgos y beneficios ha sido reconocida como esencial para proteger sus derechos y asegurar un trato ético. Objetivo. El objetivo de este artículo es realizar una revisión de la literatura sobre el consentimiento informado en la práctica médica y en la investigación clínica, identificando los avances, desafíos y consideraciones éticas asociadas, con el fin de proporcionar una comprensión integral y actualizada de su estado actual y su aplicación en diferentes contextos. Metodología. La metodología de la revisión se basó en una búsqueda sistemática de estudios en bases de datos académicas como PubMed, Scopus, y Web of Science. Se incluyeron artículos que abordaran el consentimiento informado en contextos médicos y de investigación clínica, publicados en los últimos diez años. Los estudios seleccionados fueron evaluados críticamente para identificar sesgos y extraer temas relevantes, como la comprensión del consentimiento por parte de los pacientes, las barreras culturales y la influencia de las innovaciones tecnológicas. Resultados. Los resultados de la revisión revelaron que, a pesar de los avances en la conceptualización del consentimiento informado, persisten desafíos significativos en su implementación. Estos incluyen la comprensión limitada por parte de los pacientes y participantes, barreras de comunicación, y diferencias culturales que complican el proceso de consentimiento. Se destaca la necesidad de herramientas tecnológicas y formación continua para los profesionales, así como la adaptación cultural del proceso de consentimiento para mejorar su eficacia y respetar los derechos de los individuos. Conclusión. El consentimiento informado en práctica médica y en investigación clínica es una piedra angular, su importancia no puede ser subestimada, porque en la medicina y la investigación continúan evolucionando, también debe hacerlo la práctica del consentimiento informado, adaptándose a nuevas tecnologías, desafíos éticos y las necesidades cambiantes de los pacientes y participantes. Área de estudio general: Medicina. Área de estudio específica: Bioética y ética médica. Tipo de estudio:  Artículos originales.
FGD Pengembangan Data Warehouse Pemerintah Kota Tarakan sebagai Upaya Mendukung Analisis Data
Authors: Syaddam Syaddam
Published: September 2024

Satu Data Indonesia merupakan inisiatif pemerintah Indonesia dalam menyediakan data berkualitas yang kredibel, akuntabel, dan terkini. Urgensi implementasi SDI masih dihadapi oleh banyak tantangan, seperti standar data yang tidak terpenuhi, tidak konsistennya data dan distribusi data yang sulit diakses, serta kurangnya koordinasi antara pemilik data. Untuk mengatasi masalah tersebut diperlukan pendekatan manajemen basis data secara komprehensif melalui penggunaan data warehouse untuk mendukung proses pengambilan keputusan. Dalam memastikan efektivitas pembangunan data warehouse untuk mendukung Satu Data Indonesia dibutuhkan Focus Group Discussion yang melibatkan para pemangku kepentingan terkait. FGD bertujuan untuk menjalin kesepakatan kerja (SPK) dengan para Pimpinan instansi perangkat daerah di Kota Tarakan guna mencapai hasil optimal dalam pengembangan sistem database. Metode Ceramah dan Diskusi digunakan dalam kegiatan FGD sebagai upaya pengembangan data warehouse. Kegiatan Pengabdian Masyarakat ini dilakukan oleh Dosen Politeknik Bisnis Kaltara telah berjalan sesuai rencana dengan diskusi interaktif dan partisipasi peserta yang sangat aktif.
Pelatihan Pembuatan Pupuk Organik dari Feses Sapi di PT Sanjaya Farm Bandar Lampung
Authors: Styawati Styawati , Samsugi Selamet , Indraningtyas Lathifa , Agustian Rezi Dwi , Saputra Dian Tri , Asyad Chafidz
Published: September 2024

Penggunaan pupuk kimia secara berlebihan dalam sektor pertanian telah menyebabkan masalah lingkungan seperti penurunan kesuburan tanah dan pencemaran air tanah. Pupuk kimia, yang diproduksi melalui proses industri, menggabungkan unsur hara seperti nitrogen, fosfor, dan kalium untuk kebutuhan tanaman. Sementara itu, limbah peternakan, terutama feses sapi, sering tidak dimanfaatkan dengan optimal dan dapat menjadi sumber polusi. PT Sanjaya Farm, sebuah perusahaan peternakan di Bandar Lampung, telah memanfaatkan feses sapi sebagai bahan dasar pembuatan pupuk organik, meskipun masih memerlukan peningkatan keterampilan bagi pekerja dan anggota kelompok peternak Sepakat Makmur Bersama dalam pengolahan limbah tersebut. Untuk itu, tim PKM dari Universitas Teknokrat Indonesia bekerja sama dengan dosen Universitas Lampung mengadakan pelatihan pembuatan pupuk organik dari feses sapi di PT Sanjaya Farm pada 13 Juli 2024. Pelatihan ini bertujuan meningkatkan pengetahuan dan keterampilan karyawan PT Sanjaya Farm dan kelompok peternak Sepakat Makmur Bersama dalam mengelola limbah peternakan secara efektif dan ramah lingkungan. Pelatihan yang dilakukan berhasil meningkatkan pemahaman dan keterampilan peserta terkait pembuatan pupuk organik dari feses sapi. Hal ini dibuktikan dengan hasil kuesioner yang diisi oleh peserta pelatihan sebelum pelaksanaan pelatihan dan sesudah pelaksanaan pelatihan. Berdasarkan hasil kuesioner tersebut, terdapat peningkatan pengetahuan sebesar 45,71%, hal ini menunjukkan bahwa pelatihan yang dilakukan berhasil meningkatkan pemahaman peserta tentang pembuatan pupuk organik dari feses sapi.
THE RELEASE OF PERSONS SENTENCED TO FORCED LABOR IN CONNECTION WITH THE ESTABLISHMENT OF DISABILITY
Authors: Shcherbakova Daria Sergeevna
Published: September 2024

When considering various aspects of the release of convicts from serving forced labor in connection with the recognition of the latter as disabled persons of groups I and II, insufficient legal regulation was revealed. The author focuses on such areas for improving legislation as securing the substantive right to the type of early release under study and the procedural basis for considering the issue by the court; the rights of a legal representative of a disabled person to file a petition and the powers (duties) of the administration of the correctional center to send a submission to the court for release; the possibility of bringing a released disabled person to criminal responsibility and punishment in case of failure to undergo a re-examination. The article determines the expediency of prohibiting the assignment of forced labor to persons with disabilities.
Kamu Denetçiliği Kurumu’nun kamu personel rejimi konusunda almış olduğu tavsiye kararlarını ChatGPT değerlendirebilir mi?
Authors: Akman Elvettin , Aksu Duygu , Can Yağmur
Published: September 2024

Kamu Denetçiliği Kurumu, daha yaygın bilinen adıyla Ombudsmanlık, toplumda şeffaflık ve adalet ilkesinin korunması adına denetim mekanizmasında önemli rol üstlenen bir kurum olarak değerlendirilmektedir. Bu kurum, vatandaşların kamu hizmetlerinden adil bir şekilde yararlanmasını sağlamak için önemli bir denetim aracı olarak işlev görmektedir. Özellikle, kamu personel rejimi konusunda aldığı tavsiye kararlarıyla dikkat çekmektedir. Bu kararlar, kamu kurumlarının personel politikalarını denetleyerek adaletin sağlanmasına katkıda bulunmaktadır. Kurumun yeni nesil teknolojilerden faydalanması, karar alma süreçlerinin etkinliğini artırabileceği sorusu akla gelmektedir. Örneğin, yapay zekâ teknolojisi, büyük veri setlerini hızlı ve objektif bir şekilde analiz ederek karar alma süreçlerine katkı sağlayabilir. Yapay zekâ tabanlı uygulamalar arasında yer alan ChatGPT de bu tavsiye kararlarının değerlendirilmesinde önemli bir araç olabilir. Bu teknolojilerin kullanımı, kurumun kararlarını daha kapsamlı ve etkili bir şekilde değerlendirmesine olanak tanıyabilir. Kamu Denetçiliği Kurumu tarafından alınan tavsiye kararlarının değerlendirilmesinde, ChatGPT gibi yapay zekâ tabanlı geliştirilen uygulamaların kullanımının kurum tarafından alınan tavsiye kararlarının etkinliğini ve verimliliğini artırabilir. Bu çalışma da yapay zekâ teknolojilerinden biri olan ChatGPT’nin Kamu Denetçiliği Kurumunun kararlarının değerlendirilmesindeki potansiyelini incelemeyi ve bu teknolojinin potansiyelini tartışmayı amaçlamaktadır.
Identification and validation of ferroptosis-related biomarkers in intervertebral disc degeneration
Authors: Li Chenglong , Fei Chengshuo , Le Shiyong , Lai Zhongming , Yan Bo , Wang Liang , Zhang Zhongmin
Published: September 2024

Introduction

Ferroptosis plays a significant role in intervertebral disc degeneration (IDD). Understanding the key genes regulating ferroptosis in IDD could reveal fundamental mechanisms of the disease, potentially leading to new diagnostic and therapeutic targets.

Methods

Public datasets (GSE23130 and GSE70362) and the FerrDb database were analyzed to identify ferroptosis-related genes (DE-FRGs) involved in IDD. Single-cell RNA sequencing data (GSE199866) was used to validate the specific roles and expression patterns of these genes. Immunohistochemistry and Western blot analyses were subsequently conducted in both clinical samples and mouse models to assess protein expression levels across different tissues.

Results

The analysis identified seven DE-FRGs, including MT1G, CA9, AKR1C1, AKR1C2, DUSP1, CIRBP, and KLHL24, with their expression patterns confirmed by single-cell RNA sequencing. Immunohistochemistry and Western blot analysis further revealed that MT1G, CA9, AKR1C1, AKR1C2, DUSP1, and KLHL24 exhibited differential expression during the progression of IDD. Additionally, the study highlighted the potential immune-modulatory functions of these genes within the IDD microenvironment.

Discussion

Our study elucidates the critical role of ferroptosis in IDD and identifies specific genes, such as MT1G and CA9, as potential targets for diagnosis and therapy. These findings offer new insights into the molecular mechanisms underlying IDD and present promising avenues for future research and clinical applications.
A topic model analysis of students' gendered expectations using surveyed critiques of lecturers
Authors: Kim Fiona , Johnston Emma L. , Fan Yanan
Published: September 2024

Student evaluations of teaching (SET) have been examined over the years to better understand the student experience, with an increasing portion of literature exploring the presence of implicit bias in SET surveys against minority gender and ethnic lecturers. This study explores free-text comments made by students from a large public university in Australia over the period 2010–2016, using a semi-supervised statistical approach. Data were collected via surveys administered online at the end of each course to every student officially enrolled in that course via the learning management system, and completion of the surveys was voluntary. We build a probabilistic topic model which incorporates student and lecturer characteristics into the topic formation process. We make statistical inference on the effects of gender and cultural or language backgrounds based on the topic and word prevalence probabilities. The results showed clear separation of topics discussed between male and female lecturers. From a gendered perspective, our topic analyses have found that students are significantly more likely to critique female lecturers to improve on structural aspects of the course, as well as aspects of time management and control of the lecturing environment. In comparison, male lecturers were significantly more likely to be critiqued on specific aspects related to lecture delivery. Lecturers from non-English speaking backgrounds were more likely to be both critiqued and praised for the clarity of their delivery.
Genetic support of causal association between lipid and glucose metabolism and stress urinary incontinence in women: a bidirectional Mendelian randomization and multivariable-adjusted study
Authors: Xiang Nanyan , Su Shiqi , Yang Yong , Luo Yurui , Fu Tingting , Wang Le , Lin Yifei , Huang Jin
Published: September 2024

Background

Stress urinary incontinence (SUI) is a common condition characterized by urethral sphincter failure and urine leakage. Its prevalence in women is higher than in men, and estimates of crude prevalence rates vary widely due to factors such as research methodologies, study populations, and underreporting by patients. This variability hinders research and impacts patient diagnosis, treatment, and quality of life. The complex etiology of SUI is not fully understood, and previous studies have primarily focused on non-invasive indicators. While emerging observational research suggests a correlation between SUI in women and abnormalities in lipid and blood metabolism, the underlying biological mechanisms and causal relationships require further investigation. This study aims to explore the causalities between SUI in women and lipid and blood metabolism.

Methods

Using bidirectional univariate Mendelian randomization (MR), we investigated the causal association between SUI liability in women (case/control = 5,924/399,509) from UK Biobank and lipid and glucose metabolism, indicated by total cholesterol (TC, N = 61,166), low-density lipoproteins (LDL, N = 58,381), high-density lipoproteins (HDL, N = 60,812), triglycerides (TG, N = 60,027), fasting glucose (FG, N = 19,745), and fasting insulin (FI, N = 38,238) from ENGAGE consortium. To account for potential confounding effects, multivariable MR (MVMR) analyses were performed, adjusting for body mass index (BMI) and separately among lipid and glucose metabolism.

Results

We found that increased genetically proxied TC, LDL, and HDL levels were associated with an elevated risk of SUI in women (OR: 1.090–1.117, all P < 0.05), These associations were further supported by MVMR analyses with adjustment for BMI (OR: 1.087–1.114, all P < 0.05). Conversely, increased FG and FI were associated with reduced SUI reliability in women (OR: 0.731–0.815, all P < 0.05). When adjusting among lipid and glucose metabolism, only HDL and FI demonstrated causal effects. Reverse MR analyses provided no genetic evidence supporting the causal effect of SUI in women on lipid and blood metabolism (all P > 0.05).

Conclusions

Our results reported that increased TC, LDL, and HDL are linked to higher SUI susceptibility in women, while higher FG and FI levels have a protective effect. In overweight/obese women with metabolic abnormalities, the positive associations between TC, LDL, and HDL levels and SUI indicate a higher risk.
Case Series: ATRX Variants in Four Patients with Metastatic Pheochromocytoma
Authors: Cortez Briana N. , Kuo Mickey J. M. , Jha Abhishek , Patel Mayank , Carrasquillo Jorge A. , Prodanov Tamara , Charles Kailah M. , Talvacchio Sara , Derkyi Alberta , Lin Frank I. , Taïeb David , Del Rivero Jaydira , Pacak Karel
Published: September 2024

Few reports have highlighted the rare presence of somatic ATRX variants in clinically aggressive, metastatic pheochromocytoma/paraganglioma (PCC/PGL); however, none have addressed detailed clinical presentation (including biochemistry and imaging) and management of these patients. Here, we address these clinical features and management based on four PCC patients with somatic ATRX variants from our National Institutes of Health PCC/PGL cohort. A total of 192 patients underwent exome sequencing (germline, somatic, or both), and four males were found to have somatic ATRX variants (with additional somatic VHL and FH oncogenic variants in patients 2 and 4, respectively). Per-lesion and per-patient comparisons were performed among functional imaging scans performed at the NIH. Biochemical phenotype and response to systemic treatment were evaluated. This mini-series supports prior studies showing aggressive/metastatic PCC in patients with somatic ATRX variants, as all developed widespread metastatic disease. All four PCC patients presented with noradrenergic biochemical phenotype, and some with significant elevation in 3-methoxytyramine. 18F-FDOPA PET/CT was found to be the superior functional imaging modality, with 100% lesion detection rate when compared to that of 68Ga-DOTATATE, 18F-FDG, 18F-FDA, and 123I-MIBG scans. While patients did not respond to chemotherapy or tyrosine kinase inhibitors, they responded to targeted radiotherapy using high-specific-activity 131I-MIBG (Azedra®) or 177Lu-DOTATATE (Lutathera®).
Identifying new biomarkers and potential therapeutic targets for breast cancer through the integration of human plasma proteomics: a Mendelian randomization study and colocalization analysis
Authors: Song Jingshuang , Yang Huawei
Published: September 2024

Background

The proteome is a crucial reservoir of targets for cancer treatment. While some targeted therapies have been developed, there are still significant challenges in early diagnosis and treatment, highlighting the need to identify new biomarkers and therapeutic targets for breast cancer. Therefore, we conducted a comprehensive proteome-wide Mendelian randomization (MR) study to identify novel biomarkers and potential therapeutic targets for breast cancer.

Methods

Protein quantitative trait locus (pQTL) data were extracted from two published plasma proteome-wide association studies. Genetic variants associated with breast cancer were obtained from the Breast Cancer Association Consortium, which included 133,384 cases and 113,789 controls, and the Finnish cohort study, comprising 18,786 cases and 182,927 controls. We employed summary-based MR and colocalization methods to identify potential drug targets for breast cancer, which were subsequently validated using a two-sample MR approach. Finally, a protein-protein interaction (PPI) network was constructed to detect interactions between the identified proteins and existing cancer drug targets.

Results

Gene-predicted levels of ten proteins were associated with breast cancer risk. Decreased levels of CASP8, DDX58, CPNE1, ULK3, PARK7, and BTN2A1, as well as increased levels of TNFRSF9, TNXB, DNPH1, and TLR1, were linked to an elevated risk of breast cancer. Among these, CASP8 and DDX58 were supported by tier-one evidence, while CPNE1, ULK3, PARK7, and TNFRSF9 received tier-two evidence support. The remaining proteins, TNXB, BTN2A1, DNPH1, and TLR1, were supported by tier-three evidence. CASP8, DDX58, CPNE1, ULK3, PARK7, and TNFRSF9 have already been identified as targets in drug development and potential therapeutic targets for breast cancer treatment. Additionally, ULK3 showed promise as a prognostic biomarker for breast cancer.

Conclusions

The present study identified several novel potential drug targets and biomarkers for breast cancer, providing new insights into its diagnosis and treatment. The integration of PPI and druggability evaluations enhances the prioritization of these therapeutic targets, paving the way for future drug development efforts.
Strategic management of nano-fertilizers for sustainable rice yield, grain quality, and soil health
Authors: Sahoo Bignyan Ranjan , Dash Ashish Kumar , Mohapatra Kiran Kumar , Mohanty Shraddha , Sahu Suman G. , Sahoo Bidwan Ranjan , Prusty Meenakhi , Priyadarshini Elora
Published: September 2024

Conventional fertilizers, although widely available, are relatively low in nutrient use efficiency and cause serious environmental concerns like eutrophication, greenhouse gas (GHG) emissions, nitrate poisoning, and soil pollution. With this in mind, a randomized block design (RBD) experiment was conducted in an experimental field taking 10 treatments and 3 replications to investigate the effects of integrated approaches of nano-formulated DAP fertilizer applications on rice growth, yield, and nutrient use efficiency over conventional approaches. The result revealed that plant height, panicle length, number of tillers hill−1, total number of grain panicle−1, and root length were maximum in T10 treatment (50% of the soil test recommended doses (STD) for N and P + seedling root dipping (SRD) with nano DAP at 5 mL L−1 + twice foliar sprays (FS) with nano DAP at 4 mL L−1 at 25 and 45 DAT (date after transplanting). The highest mean grain yields (4.12 and 4.05 Mg ha−1) and nutrient uptake were recorded in the T2 treatment (100% STD), but this was at par with T10 treatment. The highest benefit–cost ratio (2.26) was recorded in T10, which was 3.5% higher than T2. N and P agronomic use efficiency (AUE) ranged from 7.5% to 31.5% and 15% to 63%, and recovery efficiency (RE) ranged from 30% to 94.2% and 11.2% to 90.4%. The highest nutrient use efficiency was recorded with T10, followed by T9, and lowest in T4. Post-harvest soil pH and available N and P were significantly highest in T10. Soil MBC, MBN, MBP, urease, and phosphatase activity were found significantly higher in T2, followed by T10. The integrated application of 50% STD for N and P + SRD with nano DAP at 5 mL L-1 + twice FS with nano DAP at 4 mL L−1 at 25 and 45 DAT application can be a suitable substitute for conventional DAP and urea for rice in climate-smart agriculture as it possibly reduces environmental pollution while undisturbing crop yield over the 100% STD.
Signaling pathways and targeted therapy for rosacea
Authors: Yang Fengjuan , Wang Lian , Song Deyu , Zhang Lu , Wang Xiaoyun , Du Dan , Jiang Xian
Published: September 2024

Rosacea is a chronic skin inflammatory disease with a global prevalence ranging from 1% to 20%. It is characterized by facial erythema, telangiectasia, papules, pustules, and ocular manifestations. Its pathogenesis involves a complex interplay of genetic, environmental, immune, microbial, and neurovascular factors. Recent studies have advanced our understanding of its molecular basis, focusing on toll-like receptor (TLR) 2 pathways, LL37 expression, mammalian target of rapamycin (mTOR) activation, interleukin (IL)-17 signaling, transient receptor potential vanilloid (TRPV) functions, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. LL37-associated signaling pathways, particularly involving TLR2 and mTORC1, are critical in the pathogenesis of rosacea. LL37 interacts with signaling molecules such as extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear factor kappa B (NF-κB), inflammasomes, C-X-C motif chemokine ligand 8 (CXCL8), mas-related G-protein-coupled receptor X2 (MRGPRX2)-TRPV4, and vascular endothelial growth factor (VEGF). This interaction activates macrophages, neutrophils, mast cells, and vascular endothelial cells, leading to cytokine release including tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β, C motif chemokine ligand (CCL) 5, CXCL9, and CXCL10. These processes contribute to immune response modulation, inflammation, and angiogenesis in rosacea pathophysiology. The IL-17 signaling pathway also plays a crucial role in rosacea, affecting angiogenesis and the production of inflammatory cytokines. In addition, recent insights into the JAK/STAT pathways have revealed their integral role in inflammatory and angiogenic mechanisms associated with rosacea. Rosacea treatment currently focuses on symptom management, with emerging insights into these molecular pathways providing more targeted and effective therapies. Biological agents targeting specific cytokines, IL-17 inhibitors, JAK inhibitors, and VEGF antagonists are promising for future rosacea therapy, aiming for enhanced efficacy and fewer side effects. This review provides a comprehensive overview of the current knowledge regarding signaling pathways in rosacea and potential targeted therapeutic strategies.
New progress in pediatric allergic rhinitis
Authors: Cheng Miao , Dai Qianqian , Liu Zhi , Wang Yulin , Zhou Cuiyun
Published: September 2024

The prevalence of allergic rhinitis (AR) in children is steadily increasing, and its onset is closely associated with genetic factors, living environment, and exposure to allergens. In recent years, an increasing number of diagnostic methods have been employed to assist in diagnosing AR. In addition to pharmaceutical treatments, personalized approaches such as environmental control and allergen-specific immunotherapy are gradually gaining popularity. In this article, we reviewed recent research on the etiology, diagnostic classification, treatment methods, and health management of AR in children. These insights will benefit the implementation of personalized diagnosis and treatment for children with AR, promoting health management strategies that improve symptoms and quality of life.
Identification of novel biomarkers, shared molecular signatures and immune cell infiltration in heart and kidney failure by transcriptomics
Authors: Long Qingqing , Zhang Xinlong , Ren Fangyuan , Wu Xinyu , Wang Ze-Mu
Published: September 2024

Introduction

Heart failure (HF) and kidney failure (KF) are closely related conditions that often coexist, posing a complex clinical challenge. Understanding the shared mechanisms between these two conditions is crucial for developing effective therapies.

Methods

This study employed transcriptomic analysis to unveil molecular signatures and novel biomarkers for both HF and KF. A total of 2869 shared differentially expressed genes (DEGs) were identified in patients with HF and KF compared to healthy controls. Functional enrichment analysis was performed to explore the common mechanisms underlying these conditions. A protein-protein interaction (PPI) network was constructed, and machine learning algorithms, including Random Forest (RF), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), were used to identify key signature genes. These genes were further analyzed using Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA), with their diagnostic values validated in both training and validation sets. Molecular docking studies were conducted. Additionally, immune cell infiltration and correlation analyses were performed to assess the relationship between immune responses and the identified biomarkers.

Results

The functional enrichment analysis indicated that the common mechanisms are associated with cellular homeostasis, cell communication, cellular replication, inflammation, and extracellular matrix (ECM) production, with the PI3K-Akt signaling pathway being notably enriched. The PPI network revealed two key protein clusters related to the cell cycle and inflammation. CDK2 and CCND1 were identified as signature genes for both HF and KF. Their diagnostic value was validated in both training and validation sets. Additionally, docking studies with CDK2 and CCND1 were performed to evaluate potential drug candidates. Immune cell infiltration and correlation analyses highlighted the immune microenvironment, and that CDK2 and CCND1 are associated with immune responses in HF and KF.

Discussion

This study identifies CDK2 and CCND1 as novel biomarkers linking cell cycle regulation and inflammation in heart and kidney failure. These findings offer new insights into the molecular mechanisms of HF and KF and present potential targets for diagnosis and therapy.
Efficacy and safety of chemoradiotherapy plus immune checkpoint inhibitors for the treatment of locally advanced cervical cancer: a systematic review and meta-analysis
Authors: Zhao Zhihong , Ruan Jian , Fang Minjie , Liu Jingwen , Liao Guixiang
Published: September 2024

Background

Radiotherapy plus concurrent chemotherapy is a standard method for treating locally advanced cervical cancer (LACC). Immune checkpoint inhibitors (ICIs) are widely applied in the treatment of recurrent cervical cancer, metastatic cervical cancer or LACC. The efficacy and safety of radiotherapy plus immunotherapy for LACC require further investigation. The objective of this review and meta-analysis was to analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with ICIs for treating LACC on the basis of the results of randomized controlled trials (RCTs).

Methods

We comprehensively searched electronic databases to identify RCTs that focused on CCRT plus ICIs for LACC treatment. The outcomes included the objective response rate (ORR) and progression-free survival (PFS), overall survival (OS) and adverse events (AEs). A standard method for systematic review and meta-analysis was used. Review Manager 5.4 was used for data combination and analyses.

Results

Three RCTs involving 1882 participants with LACC were identified and included in the systematic review and meta-analysis. CCRT plus ICIs improved the rates of PFS (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: CI: 0.64, 0.91, P = 0.002) and OS (HR: 0.7695% CI (95% CI 0.58–0.99, P = 0.04) in patients with LACC. Compared with the control group, the CCRT plus immunotherapy group had an increased ORR (OR: 1.37, 95% CI: 1.02,1.85, P=0.04). The two methods had similar rates (HR=1.99, 95% CI: 0.99, 1.43; P=0.07) of treatment-related grade 3 or higher AEs. The CCRT plus immunotherapy group had a higher rate than did the control group (HR: 2.68, 95% CI: 1.38, 5.21; P=0.004) in terms of any grade immunotherapy-related AEs.

Conclusions

CCRT plus ICIs is efficacious and safe for the management of LACC. The addition of ICIs to CCRT improved the rates of PFS and OS in patients with LACC. The adverse effects of immunotherapy-related AEs should be strictly examined and managed in a timely manner.
Comprehensive analysis of stearoyl-coenzyme A desaturase in prostate adenocarcinoma: insights into gene expression, immune microenvironment and tumor progression
Authors: Wang Jie , Ying Liang , Xiong He , Zhou Duan-Rui , Wang Yi-Xuan , Che Hui-Lian , Zhong Zhang-Feng , Wu Guo-Sheng , Ge Yun-Jun
Published: September 2024

Prostate adenocarcinoma (PRAD) is a prevalent global malignancy which depends more on lipid metabolism for tumor progression compared to other cancer types. Although Stearoyl-coenzyme A desaturase (SCD) is documented to regulate lipid metabolism in multiple cancers, landscape analysis of its implications in PRAD are still missing at present. Here, we conducted an analysis of diverse cancer datasets revealing elevated SCD expression in the PRAD cohort at both mRNA and protein levels. Interestingly, the elevated expression was associated with SCD promoter hypermethylation and genetic alterations, notably the L134V mutation. Integration of comprehensive tumor immunological and genomic data revealed a robust positive correlation between SCD expression levels and the abundance of CD8+ T cells and macrophages. Further analyses identified significant associations between SCD expression and various immune markers in tumor microenvironment. Single-cell transcriptomic profiling unveiled differential SCD expression patterns across distinct cell types within the prostate tumor microenvironment. The Gene Ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that SCD enriched pathways were primarily related to lipid biosynthesis, cholesterol biosynthesis, endoplasmic reticulum membrane functions, and various metabolic pathways. Gene Set Enrichment Analysis highlighted the involvement of elevated SCD expression in crucial cellular processes, including the cell cycle and biosynthesis of cofactors pathways. In functional studies, SCD overexpression promoted the proliferation, metastasis and invasion of prostate cancer cells, whereas downregulation inhibits these processes. This study provides comprehensive insights into the multifaceted roles of SCD in PRAD pathogenesis, underscoring its potential as both a therapeutic target and prognostic biomarker.
An evolutionarily conserved function of C-reactive protein is to prevent the formation of amyloid fibrils
Authors: Agrawal Alok , Pathak Asmita , Ngwa Donald N. , Thirumalai Avinash , Armstrong Peter B. , Singh Sanjay K.
Published: September 2024

C-reactive protein (CRP) binds to phosphocholine (PCh)-containing substances and subsequently activates the complement system to eliminate the ligand. The PCh-binding function of CRP has been conserved throughout evolution from arthropods to humans. Human CRP, in its structurally altered conformation at acidic pH, also binds to amyloid-β (Aβ) and prevents the formation of Aβ fibrils. It is unknown whether the Aβ-binding function of CRP has also been evolutionarily conserved. The aim of this study was to determine whether CRP isolated from American horseshoe crab Limulus polyphemus was also anti-amyloidogenic and whether this function required structural alteration of Limulus CRP (Li-CRP). Two CRP species Li-CRP-I and Li-CRP-II were purified from hemolymph by employing PCh-affinity chromatography and phosphoethanolamine-affinity chromatography, respectively. Both Li-CRP-I and Li-CRP-II bound to immobilized Aβ at physiological pH. Unlike human CRP, Li-CRP did not require any changes in its overall structure to bind to Aβ. Both Li-CRP-I and Li-CRP-II bound to Aβ in the fluid phase also and prevented the fibrillation of Aβ. Additionally, ion-exchange chromatography of purified Li-CRP indicated that a variety of Li-CRP molecules of different subunit compositions were present in Limulus hemolymph, raising the possibility that the presence of various Li-CRP species in hemolymph facilitates the recognition of a range of proteins with differing amyloidogenicity. We conclude that the binding of CRP to Aβ is an ancient function of CRP. In invertebrates, the Aβ-binding function of CRP can protect the host from toxicity caused by amyloidogenic and pathogenic proteins. In humans, the Aβ-binding function of CRP can protect against inflammatory diseases in which the host proteins are ectopically deposited on either host cells or foreign cells in an inflammatory milieu since immobilized proteins may expose Aβ-like structures after deposition at places where they are not supposed to be.
Urolithin A alleviates cell senescence by inhibiting ferroptosis and enhances corneal epithelial wound healing
Authors: Guo Xiao-Xiao , Chang Xue-Jiao , Pu Qi , Li Ao-Ling , Li Jing , Li Xin-Yu
Published: September 2024

Purpose

To analyze the therapeutic effect and mechanism of Urolithin A (UA) on delayed corneal epithelial wound healing.

Methods

The C57BL/6 mice were continuously exposed to hyperosmotic stress (HS) for 7 days followed by the removal of central corneal epithelium to establish a delayed corneal epithelial wound healing model in vivo. In vitro, the human corneal epithelial cell line (HCE-T) was also incubated under HS. UA was administered in vivo and in vitro to study its effects on corneal epithelial cells. Senescence-associated β-galactosidase (SA-β-gal) staining was performed to detect the level of cell senescence. Transcriptome sequencing (RNA-seq) was conducted to elucidate the molecular mechanism underlying the effect of UA on corneal epithelial repair. Additionally, the expression of senescence-related and ferroptosis-related genes and the levels of lipid peroxides (LPO) and malondialdehyde (MDA) were measured.

Results

Hyperosmotic stress (HS) significantly increased the proportion of SA-β-gal staining positive cells in corneal epithelial cells and upregulated the expression of p16 and p21 (p < 0.0001). Topical application of UA decreased the accumulation of senescent cells in corneal epithelial wounds and promoted epithelial wound healing. The results of RNA-seq of HS-induced corneal epithelial cells showed that the ferroptosis pathway was significantly dysregulated. Further investigation revealed that UA decreased the level of oxidative stress in HCE-T cells, including the levels of LPO and MDA (p < 0.05). Inhibition of ferroptosis significantly prevented cellular senescence in HS-induced HCE-T cells.

Conclusion

In this study, UA promoted HS-induced delayed epithelial wound healing by reducing the senescence of corneal epithelial cells through the inhibition of ferroptosis.
Analysis of soft rot Pectobacteriaceae population diversity in US potato growing regions between 2015 and 2022
Authors: Ma Xing , Zhang Xiuyan , Stodghill Paul , Rioux Renee , Shrestha Smita , Babler Brooke , Rivedal Hannah , Frost Kenneth , Hao Jianjun , Secor Gary , Swingle Bryan
Published: September 2024

Introduction

Soft rot Pectobacteriaceae (SRP) bacteria are globally dispersed pathogens that cause significant economic loss in potato and other crops. Our understanding of the SRP species diversity has expanded in recent years due to advances and adoption of whole-genome sequence technologies. There are currently 34 recognized SRP species that belong to the Dickeya and Pectobacterium genera.

Methods

We used whole-genome sequencing based analysis to describe the current distribution and epidemiology of SRP isolated from diseased potato samples obtained from commercial potato cropping systems in the United States. Our primary objectives in the present study were to: (1) identify the species of these SRP isolates recovered from potato samples across 14 states in the US, (2) describe the variation among SRP isolates from various US locations and track their temporal changes, and (3) evaluate the evolutionary relationships among these SRP isolates to deduce their source. We collected 118 SRP strains from diseased potato plants and tubers in 14 states between 2015 and 2022.

Results

We identified three Dickeya and eight Pectobacterium species from diseased potato samples. Dickeya dianthicola, Pectobacterium parmentieri, P. carotovorum, and P. versatile appeared to be the predominant species, constituting 83% of the isolates. Furthermore, all D. dianthicola strains studied here as well as 90% of US D. dianthicola isolates sequenced to date exhibit significant clonality.

Discussion

The prevalence of this specific group of D. dianthicola, temporally and geographically, aligns with the occurrence of blackleg and soft rot outbreaks in the northeastern US after 2014. The genomic diversity observed in P. parmentieri implies multiple introductions to the US from at least four distinct sources, earlier than the arrival of the predominant group of D. dianthicola. In contrast, P. carotovorum and P. versatile appear to be widespread, long-term endemic strains in the US.
Functional analysis of microorganisms and metabolites in the cecum of different sheep populations and their effects on production traits
Authors: Meng Quanlu , Tang Zhixiong , Yang Feifei , Shi Jinping , Liu Ting , Cheng Shuru
Published: September 2024

The purpose of this study was to investigate the effects of intestinal microbiota on the growth and production performance of different groups of sheep, focusing on the role of cecal microbiota in regulating intestinal function, enhancing digestion and absorption, and improving feed utilization. The production performance of MG × STH (Mongolia × Small Tailed Han) F1 hybrids and purebred STH (Small Tailed Han) sheep by measuring various factors, including enzyme activities and VFAs (volatile fatty acids), to analyze changes in cecal fermentation parameters across different sheep groups. Metagenomic and metabolomic sequencing combined with bioinformatics to analyze the cecal contents of the two sheep populations. The study findings indicated that the MG × STH F1 hybrids outperformed the purebred STH in terms of body weight, height, oblique body length, and VFAs (p < 0.05). Additionally, the MG × STH F1 higher levels of protease and cellulase in the cecum compared to the purebred sheep (p < 0.05). Metagenomic analysis identified 4,034 different microorganisms at the species level. Five differential organisms (Akkermansiaceae bacterium, Escherichia coli, unclassified p Firmicutes, Streptococcus equinus, Methanobrevibacter millerae) positively regulated sheep performance. Metabolomics identified 822 differential metabolites indoleacetaldehyde, 2-aminobenzoic acid, phenyl-Alanine, enol-phenylpyruvate and n-acetylserotonin were associated with improved performance of sheep. The combined results from the metagenomic and metabolomic studies suggest a positive correlation between specific microbes and metabolites and the performance of the sheep. In conclusion, the MG × STH F1 hybrids demonstrated superior growth performance compared to the purebred STH sheep. The identified microorganisms and metabolites have promising roles in positively regulating sheep growth and can be considered key targets for enhancing sheep performance.
In silico analysis of secreted effectorome of the rubber tree pathogen Rigidoporus microporus highlights its potential virulence proteins
Authors: Longsaward Rawit , Viboonjun Unchera , Wen Zilan , Asiegbu Fred O.
Published: September 2024

Rigidoporus microporus, the causative agent of the white root rot disease of rubber trees, poses a significant threat to natural rubber production worldwide. Understanding the molecular mechanisms facilitating its pathogenicity would be crucial for developing effective disease management strategies. The pathogen secretes effector proteins, which play pivotal roles in modulating host immune responses and infection. In this study, in silico analyses identified 357 putative secreted effector proteins from the R. microporus genome. These were then integrated into previous RNA-seq data obtained in response to rubber tree latex exposure. Annotation of putative effectors suggested the abundance of proteins in several families associated with the virulence of R. microporus, especially hydrophobin proteins and glycoside hydrolase (GH) proteins. The contribution of secreted effectors to fungal pathogenicity was discussed, particularly in response to rubber tree latex exposure. Some unknown highly expressed effectors were predicted for the protein structures, revealing their similarity to aminopeptidase, ubiquitin ligase, spherulin, and thaumatin protein. This integrative study further elucidates the molecular mechanism of R. microporus pathogenesis and offers alternative targets for developing control strategies for managing white root rot disease in rubber plantations.
Subthreshold amyloid deposition, cerebral small vessel disease, and functional brain network disruption in delayed cognitive decline after stroke
Authors: Lim Jae-Sung , Lee Jae-Joong , Kim Geon Ha , Kim Hang-Rai , Shin Dong Woo , Lee Keon-Joo , Baek Min Jae , Ko Eunvin , Kim Beom Joon , Kim SangYun , Ryu Wi-Sun , Chung Jinyong , Kim Dong-Eog , Gorelick Philip B. , Woo Choong-Wan , Bae Hee-Joon
Published: September 2024

Background

Although its incidence is relatively low, delayed-onset post-stroke cognitive decline (PSCD) may offer valuable insights into the “vascular contributions to cognitive impairment and dementia,” particularly concerning the roles of vascular and neurodegenerative mechanisms. We postulated that the functional segregation observed during post-stroke compensation could be disrupted by underlying amyloid pathology or cerebral small vessel disease (cSVD), leading to delayed-onset PSCD.

Methods

Using a prospective stroke registry, we identified patients who displayed normal cognitive function at baseline evaluation within a year post-stroke and received at least one subsequent assessment. Patients suspected of pre-stroke cognitive decline were excluded. Decliners [defined by a decrease of ≥3 Mini-Mental State Examination (MMSE) points annually or an absolute drop of ≥5 points between evaluations, confirmed with detailed neuropsychological tests] were compared with age- and stroke severity-matched non-decliners. Index-stroke MRI, resting-state functional MRI, and 18F-florbetaben PET were used to identify cSVD, functional network attributes, and amyloid deposits, respectively. PET data from age-, sex-, education-, and apolipoprotein E-matched stroke-free controls within a community-dwelling cohort were used to benchmark amyloid deposition.

Results

Among 208 eligible patients, 11 decliners and 10 matched non-decliners were identified over an average follow-up of 5.7 years. No significant differences in cSVD markers were noted between the groups, except for white matter hyperintensities (WMHs), which were strongly linked with MMSE scores among decliners (rho = −0.85, p < 0.01). Only one decliner was amyloid-positive, yet subthreshold PET standardized uptake value ratios (SUVR) in amyloid-negative decliners inversely correlated with final MMSE scores (rho = −0.67, p = 0.04). Decliners exhibited disrupted modular structures and more intermingled canonical networks compared to non-decliners. Notably, the somato-motor network’s system segregation corresponded with the decliners’ final MMSE (rho = 0.67, p = 0.03) and was associated with WMH volume and amyloid SUVR.

Conclusion

Disruptions in modular structures, system segregation, and inter-network communication in the brain may be the pathophysiological underpinnings of delayed-onset PSCD. WMHs and subthreshold amyloid deposition could contribute to these disruptions in functional brain networks. Given the limited number of patients and potential residual confounding, our results should be considered hypothesis-generating and need replication in larger cohorts in the future.