bluuebunny/crossref_metadata_2025 huggingface dataset:
Causas da redução das taxas de imunização entre crianças no município de Cascavel e suas implicâncias na saúde pública do Brasil na prevenção de doenças
Authors: Fernandes Paola Tolotti , Lima Urielly Tayná da Silva , Scherer Eduarda Elsenbach , Batistello Maria Eduarda de Quadros , Cerutti Naila
Published: May 2024

Introdução: A vacinação é fundamental para prevenir doenças graves e sua propagação. Apesar do amplo Programa Nacional de Imunizações (PNI) no Brasil, as taxas de vacinação infantil têm caído, aumentando o risco de ressurgimento de doenças erradicadas. É crucial promover a conscientização sobre a importância da vacinação e causa dessa redução para garantir a proteção de toda a população. Objetivo: Estabelecer quais as causas da redução da taxa de imunizações entre crianças até os 12 anos no município de Cascavel e analisar quais as implicações futuras na saúde pública geral do Brasil. Métodos:  Estudo do tipo transversal quantitativo e qualitativo, com o foco em levantar dados mediante aplicação de um questionário pela plataforma Google Forms®, voltado aos pais ou tutores de crianças dos 0 aos 12 anos, independe do sexo e de diferentes regiões do município de Cascavel. Resultados: Foram analisadas 160 respostas ao questionário. Dessas 160 respostas, 100% dos tutores haviam vacinado seus filhos, porém dos 59 que foram questionados, 60,3% alegam que algum conhecido já deixou de imunizar as crianças sob seus cuidados. Vale ressaltar que apesar 86% dos colaboradores já terem buscado informação sobre vacinação e 95% considerarem elas verdadeiramente eficazes, 46,3% já sentiu algum tipo de insegurança em relação aos imunizantes e 70% já leu e reconheceu algum tipo de fake news, disseminadas principalmente pelas redes sociais como demonstra a pesquisa. Conclusão: Com este estudo, conclui-se que apesar do amplo conhecimento disponível em relação aos imunizantes ainda existe hesitação em relação a vacinação, desencadeada de forma prevalente pelas fake news como também pela falta de conhecimento, medo e insegurança acerca de seus efeitos colaterais.
PENDAMPINGAN PENERAPAN METODE KAUNY DALAM PEMBELAJARAN AL-QURAN PADA LEMBAGA PENDIDIKAN
Authors: Shaharoh Almas Syafa , Irham Irham , Mulyadi Acep , Rohayah Aulia
Published: May 2024

The implementation of this community service focuses on increasing the enthusiasm for reading and memorizing the Qur'an through the Qur'an learning process using the Kauny method so that children feel comfortable, happy and relaxed in learning the Qur'an in terms of getting used to reading and then getting used to memorizing the Qur'an. The author conducted two stages of writing methods of socialization and beginner training in the process of learning the Qur'an using the Kauny method. The findings of this study are by applying the Kauny method to TPQ children in Wibawamulya village makes them enthusiastic in memorizing, not easily bored and saturated because of the nature of learning that is not monotonous. And in each lesson there is a story that describes the verse being studied, making it easier for children to imagine and explore the verse and its meaning through movement. This is able to sharpen their brain power in the memorization process.
SOSIALISASI LITERASI DAN LEMBAGA KEUANGAN SYARIAH PADA MASYARAKAT DESA SUKABUNGAH
Authors: Aulia Salwa Afronisa , Maemunah Umi Khana , Putra Purnama , Tirtajaya Mas Deden
Published: May 2024

This community service activity aims to educate the public about sharia finance. The main target of this sharia financial literacy socialization activity is the community in Sukabungah Village, Bojongmangu District, Bekasi Regency. The activities were carried out in the form of seminars by the community service implementation team at Islamic University 45 Bekasi. from the results of observations and interviews, the existence of Bank Emok (Lentenir) in Sukabungah Village still exists today, this is proven by the fact that 60% of the community is ensnared by loan sharks and even online loans (pinjol) this occurs because of the lack of understanding of the people of Sukabungah Village regarding sharia finance. . Therefore, in Community Service activities, the service team plans to carry out outreach through seminars related to sharia finance. After holding sharia finance socialization activities through seminars, the Sukabungah village community gained new knowledge about sharia finance, thereby increasing knowledge and information about sharia finance, managing and managing finances well and being aware of the negative effects of using loan sharks and interest-bearing loans.
EDUKASI DAMPAK PERNIKAHAN DINI DI DESA RIDOMANAH
Authors: Damayanti Ema , Ash Shabah Musyaffa Amin , Suprihatin Suprihatin
Published: May 2024

Early marriage is a marriage that is carried out by early childhood or has not reached the age allowed for marriage. In law, marriage is allowed when you reach the age of 19 years. However, there are still many people who practice early marriage, especially rural communities. Early marriage has many impacts, one of which is the failure of child growth and development or stunting. In this community service, the goal is to prevent early childhood marriage and stunting in Ridomanah village. In this activity, the subject is students of SMPN 2 Cibarusah, the implementation method is community education with socialization of the impact of early marriage. Based on the percentage of pre-test and post-test results, student knowledge has increased significantly, from 64.20% to 85.40%.  This socialization activity on the impact of early marriage at SMPN 2 Cibarusah is quite effective and successful in increasing students' knowledge about the impact of early marriage.
Untangling Systemic Mastocytosis: An Update on Challenges in the Diagnosis and Treatment of Myeloid Neoplasms with Systemic Mastocytosis
Authors: Solary Eric , Rossignol Julien , Reiter Andreas , Radia Deepti
Published: May 2024

This symposium was held on the first day of the 2023 European Hematology Association (EHA) Congress, held in Frankfurt, Germany. The main objective of the symposium was to gather experts from the field to raise awareness of the challenges in diagnosing and treating systemic mastocytosis (SM) with an associated haematologic neoplasm (AHN). Presentations focused on optimising the diagnosis of the SM component and recognising the different types of myeloid AHN. The expert panel considered the clinical management of SM-AHN, and how and when to prioritise the various disease components.

The overarching message from the symposium was that diagnosis of SM-AHN is challenging, and SM is often missed in patients with a myeloid neoplasm, such as chronic myelomonocytic leukaemia (CMML), myelodysplastic/myeloproliferative neoplasm (MDS/MPN), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN), as well as AHN being missed in patients with SM. Identification of a SM-AHN through serum tryptase and/or molecular testing for KITD816V mutation in peripheral blood in a patient with a previous diagnosis of a myeloid neoplasm allows potentially efficacious targeted treatment with KIT inhibitors, such as midostaurin and avapritinib. Although SM-AHN is associated with a poor prognosis, a correct diagnosis and detailed understanding of an individual’s disease can help to guide optimal treatment decisions, including when to prioritise SM treatment over AHN treatment, and vice versa.
Special issue on methods in visual politics and protest
Authors: Özkula Suay Melisa , Schlussel Hadas , Divon Tom , Slavnić Danka Ninković
Published: May 2024

This special issue forms the second part of a double issue on methods in visual politics and protest. It draws together five articles that provide new pathways for deconstructing visual political narratives and offers reflexive and nuanced accounts for researching visual data and information shared on social media platforms (here: TikTok, Instagram, Twitter/X, Facebook). They do so through the application of feminist mixed methods (femmix), cross-platform analysis, and context-aware, comparative, and triangulated approaches. Taken together, the double issue offers a substantive compendium of articles exploring the latest methodological developments in visual politics and protest.
A sono-responsive antibacterial nanosystem co-loaded with metformin and bone morphogenetic protein-2 for mitigation of inflammation and bone loss in experimental peri-implantitis
Authors: Hu Bo , Qiao Wang , Cao Yang , Fu Xiaoming , Song Jinlin
Published: May 2024

Background

Dental implants have become an increasingly popular option for replacing missing teeth, and the prevalence of peri-implantitis has also increased, which is expected to become a public health problem worldwide and cause high economic and health burdens. This scenario highlights the need for new therapeutic options to treat peri-implantitis.

Methods

In this study, we proposed a novel sono-responsive antibacterial nanosystem co-loaded with metformin (Met) and bone morphogenetic protein-2 (BMP-2) to promote efficacy in treating peri-implantitis. We introduced the zeolitic imidazolate framework-8 (ZIF-8) as a carrier for hematoporphyrin monomethyl ether (HMME) to enhance the antibacterial effect of sonodynamic antibacterial therapy and tested its reactive oxygen species (ROS) production efficiency and bactericidal effect in vitro. Afterward, HMME-loaded ZIF-8, BMP-2-loaded polylactic acid-glycolic acid (PLGA), and Met were incorporated into gelatin methacryloyl (GelMA) hydrogels to form HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels, and the biocompatibility of which was determined in vitro and in vivo. A bacterial-induced peri-implantitis model in the maxilla of rats was established to detect the effects of the composite hydrogels with adjunctive use of ultrasound on regulating inflammation and promoting bone tissue repair in vivo.

Results

The results indicated that HMME@ZIF-8 with ultrasound stimulation demonstrated more better ROS production efficiency and antimicrobial efficacy. The composite hydrogels had good biocompatibility. Ultrasound-assisted application of the composite hydrogels reduced the release of the inflammatory factors IL-6 and TNF-α and reduced bone loss around the implant in rats with bacterial-induced peri-implantitis.

Conclusion

Our observations suggest that HMME@ZIF-8 may be a new good sonosensitizer material for sonodynamic antibacterial therapy. The use of HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels in combination with ultrasound can provide a novel option for treating peri-implantitis in the future.
Involvement of N4BP2L1, PLEKHA4, and BEGAIN genes in breast cancer and muscle cell development
Authors: Dastsooz Hassan , Anselmi Francesca , Lauria Andrea , Cicconetti Chiara , Proserpio Valentina , Mohammadisoleimani Elham , Firoozi Zahra , Mansoori Yaser , Haghi-Aminjan Hamed , Caizzi Livia , Oliviero Salvatore
Published: May 2024

Patients with breast cancer show altered expression of genes within the pectoralis major skeletal muscle cells of the breast. Through analyses of The Cancer Genome Atlas (TCGA)-breast cancer (BRCA), we identified three previously uncharacterized putative novel tumor suppressor genes expressed in normal muscle cells, whose expression was downregulated in breast tumors. We found that NEDD4 binding protein 2-like 1 (N4BP2L1), pleckstrin homology domain-containing family A member 4 (PLEKHA4), and brain-enriched guanylate kinase-associated protein (BEGAIN) that are normally highly expressed in breast myoepithelial cells and smooth muscle cells were significantly downregulated in breast tumor tissues of a cohort of 50 patients with this cancer. Our data revealed that the low expression of PLEKHA4 in patients with menopause below 50 years correlated with a higher risk of breast cancer. Moreover, we identified N4BP2L1 and BEGAIN as potential biomarkers of HER2-positive breast cancer. Furthermore, low BEGAIN expression in breast cancer patients with blood fat, heart problems, and diabetes correlated with a higher risk of this cancer. In addition, protein and RNA expression analysis of TCGA-BRCA revealed N4BP2L1 as a promising diagnostic protein biomarker in breast cancer. In addition, the in silico data of scRNA-seq showed high expression of these genes in several cell types of normal breast tissue, including breast myoepithelial cells and smooth muscle cells. Thus, our results suggest their possible tumor-suppressive function in breast cancer and muscle development.
Population-wide impact of a pragmatic program to identify and manage individuals at high-risk of cardiovascular disease: a cluster randomized trial in 120 villages from Northern China
Authors: Chen Siyu , Yan Lijing L. , Feng Xiangxian , Zhang Jianxin , Zhang Yuhong , Zhang Ruijuan , Zhou Bo , Wu Yangfeng
Published: May 2024

Objectives

To explore the population-wide impacts of an evidence-based high-risk strategy for prevention of cardiovascular diseases in resource-poor populations.

Methods

A cluster randomized controlled trial was conducted among 120 villages in rural China, with 60 on intervention and 60 on usual care as controls, for 2 years. The intervention emphasized training village doctors to identify high-risk individuals and administering standardized treatments focusing on hypertension management. A random sample of 20 men aged ≥50 years and 20 women aged ≥60 years was drawn from each village before randomization for the baseline survey, and another independent random sample with the same age and sex distribution was drawn at 2 years for the post-intervention survey. The primary outcome was the population mean systolic blood pressure (SBP). Secondary outcomes included the proportions of patients who received regular primary care, antihypertensive medications, aspirin, or lifestyle advice.

Results

A total of 5,654 high cardiovascular risk individuals were identified and managed by village doctors in intervention villages for 15 months on average, with mean SBP lowered by 19.8 mmHg and the proportion with blood pressure under control increased from 22.1% to 72.7%. The primary analysis of the two independent samples (5,050 and 4,887 participants each) showed that population-wide mean SBP in intervention villages did not differ from that in control villages at 2 years (mean difference = 1.0 mmHg, 95% CI: −2.19, 4.26; P = 0.528), though almost all secondary outcomes concerning primary care indicators significantly increased in intervention villages.

Conclusions

In our study, the pragmatic cardiovascular risk management program targeting on high-risk individuals significantly improved the quality of primary care. However, its impact on population blood pressure level and the burden of hypertension-related diseases appeared very limited.

Clinical Trial Registration

ClinicalTrial.gov identifier, NCT01259700.
Case Report: Asymptomatic SARS-COV2 infection triggering recurrent Takotsubo syndrome
Authors: Dall’Ara Gianni , Compagnone Miriam , Carletti Roberto , Piciucchi Sara , Gardini Elisa , Galvani Marcello
Published: May 2024

Takotsubo syndrome (TTS) is a rare disease mimicking acute coronary syndrome, often triggered by physical or emotional stress, and characterized by transient left ventricular dysfunction. Recurrences are described in about 5% of cases and may have different clinical and imaging patterns. In the present report, SARS-COV-2 infection, even in the absence of symptoms and overt emotional stress, seems correlated with recurrence of TTS, due to the absence of other recognized triggers. The hypothesis is that in predisposed patients, events like catecholamine-induced myocyte injury, direct viral damage, cytokine storm, immune-mediated damage, and procoagulant state, all possibly induced by the infection, may elicit endothelial dysfunction as substrate for TTS onset.
Comprehensive machine learning models for predicting therapeutic targets in type 2 diabetes utilizing molecular and biochemical features in rats
Authors: Matboli Marwa , Al-Amodi Hiba S. , Khaled Abdelrahman , Khaled Radwa , Roushdy Marian M. S. , Ali Marwa , Diab Gouda Ibrahim , Elnagar Mahmoud Fawzy , Elmansy Rasha A. , TAhmed Hagir H. , Ahmed Enshrah M. E. , Elzoghby Doaa M. A. , M.Kamel Hala F. , Farag Mohamed F. , ELsawi Hind A. , Farid Laila M. , Abouelkhair Mariam B. , Habib Eman K. , Fikry Heba , Saleh Lobna A. , Aboughaleb Ibrahim H.
Published: May 2024

Introduction

With the increasing prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need to discover effective therapeutic targets for this complex condition. Coding and non-coding RNAs, with traditional biochemical parameters, have shown promise as viable targets for therapy. Machine learning (ML) techniques have emerged as powerful tools for predicting drug responses.

Method

In this study, we developed an ML-based model to identify the most influential features for drug response in the treatment of type 2 diabetes using three medicinal plant-based drugs (Rosavin, Caffeic acid, and Isorhamnetin), and a probiotics drug (Z-biotic), at different doses. A hundred rats were randomly assigned to ten groups, including a normal group, a streptozotocin-induced diabetic group, and eight treated groups. Serum samples were collected for biochemical analysis, while liver tissues (L) and adipose tissues (A) underwent histopathological examination and molecular biomarker extraction using quantitative PCR. Utilizing five machine learning algorithms, we integrated 32 molecular features and 12 biochemical features to select the most predictive targets for each model and the combined model.

Results and discussion

Our results indicated that high doses of the selected drugs effectively mitigated liver inflammation, reduced insulin resistance, and improved lipid profiles and renal function biomarkers. The machine learning model identified 13 molecular features, 10 biochemical features, and 20 combined features with an accuracy of 80% and AUC (0.894, 0.93, and 0.896), respectively. This study presents an ML model that accurately identifies effective therapeutic targets implicated in the molecular pathways associated with T2DM pathogenesis.
The metabolic characteristics and changes of chondrocytes in vivo and in vitro in osteoarthritis
Authors: Adam Miradj Siddick , Zhuang Huangming , Ren Xunshan , Zhang Yuelong , Zhou Panghu
Published: May 2024

Osteoarthritis (OA) is an intricate pathological condition that primarily affects the entire synovial joint, especially the hip, hand, and knee joints. This results in inflammation in the synovium and osteochondral injuries, ultimately causing functional limitations and joint dysfunction. The key mechanism responsible for maintaining articular cartilage function is chondrocyte metabolism, which involves energy generation through glycolysis, oxidative phosphorylation, and other metabolic pathways. Some studies have shown that chondrocytes in OA exhibit increased glycolytic activity, leading to elevated lactate production and decreased cartilage matrix synthesis. In OA cartilage, chondrocytes display alterations in mitochondrial activity, such as decreased ATP generation and increased oxidative stress, which can contribute to cartilage deterioration. Chondrocyte metabolism also involves anabolic processes for extracellular matrix substrate production and energy generation. During OA, chondrocytes undergo considerable metabolic changes in different aspects, leading to articular cartilage homeostasis deterioration. Numerous studies have been carried out to provide tangible therapies for OA by using various models in vivo and in vitro targeting chondrocyte metabolism, although there are still certain limitations. With growing evidence indicating the essential role of chondrocyte metabolism in disease etiology, this literature review explores the metabolic characteristics and changes of chondrocytes in the presence of OA, both in vivo and in vitro. To provide insight into the complex metabolic reprogramming crucial in chondrocytes during OA progression, we investigate the dynamic interaction between metabolic pathways, such as glycolysis, lipid metabolism, and mitochondrial function. In addition, this review highlights prospective future research directions for novel approaches to diagnosis and treatment. Adopting a multifaceted strategy, our review aims to offer a comprehensive understanding of the metabolic intricacies within chondrocytes in OA, with the ultimate goal of identifying therapeutic targets capable of modulating chondrocyte metabolism for the treatment of OA.
Exploring the impact of demand and supply-side interventions on energy decarbonization of freight transportation: a research based on G20 nations
Authors: Zhang Boyuan
Published: May 2024

Through quantitative modeling, the study established a dynamic supply and demand system from freight demand, renewable energy production, alternative new energy, renewable energy consumption and carbon dioxide emissions to assess the impact of demand-side and supply-side changes on energy decarbonization. The results indicate that adjusting the freight volumes of railway and aviation, renewable energy electricity supply, and the use of alternative new energy sources have varying degrees of impact on decarbonization in transportation. Through interventions on the demand side of freight volumes, CO2 emissions from transportation decrease to levels below those before the intervention-induced fluctuations, while consumption of renewable energy increases to levels above those before the adjustment.
Genome-wide association analysis of the resistance to infectious hematopoietic necrosis virus in two rainbow trout aquaculture lines confirms oligogenic architecture with several moderate effect quantitative trait loci
Authors: Palti Yniv , Vallejo Roger L. , Purcell Maureen K. , Gao Guangtu , Shewbridge Kristy L. , Long Roseanna L. , Setzke Christopher , Fragomeni Breno O. , Cheng Hao , Martin Kyle E. , Naish Kerry A.
Published: May 2024

Infectious hematopoietic necrosis (IHN) is a disease of salmonid fish that is caused by the IHN virus (IHNV), which can cause substantial mortality and economic losses in rainbow trout aquaculture and fisheries enhancement hatchery programs. In a previous study on a commercial rainbow trout breeding line that has undergone selection, we found that genetic resistance to IHNV is controlled by the oligogenic inheritance of several moderate and many small effect quantitative trait loci (QTL). Here we used genome wide association analyses in two different commercial aquaculture lines that were naïve to previous exposure to IHNV to determine whether QTL were shared across lines, and to investigate whether there were major effect loci that were still segregating in the naïve lines. A total of 1,859 and 1,768 offspring from two commercial aquaculture strains were phenotyped for resistance to IHNV and genotyped with the rainbow trout Axiom 57K SNP array. Moderate heritability values (0.15–0.25) were estimated. Two statistical methods were used for genome wide association analyses in the two populations. No major QTL were detected despite the naïve status of the two lines. Further, our analyses confirmed an oligogenic architecture for genetic resistance to IHNV in rainbow trout. Overall, 17 QTL with notable effect (≥1.9% of the additive genetic variance) were detected in at least one of the two rainbow trout lines with at least one of the two statistical methods. Five of those QTL were mapped to overlapping or adjacent chromosomal regions in both lines, suggesting that some loci may be shared across commercial lines. Although some of the loci detected in this GWAS merit further investigation to better understand the biological basis of IHNV disease resistance across populations, the overall genetic architecture of IHNV resistance in the two rainbow trout lines suggests that genomic selection may be a more effective strategy for genetic improvement in this trait.
Treatment patterns in a real-world cohort of patients with Wilson disease in the United States
Authors: Medici Valentina , Kebede Nehemiah , Stephens Jennifer , Kunjappu Mary , Vierling John M.
Published: May 2024

Background

Wilson disease (WD) is a rare and potentially fatal genetic disorder caused by accumulation of toxic levels of copper. Current treatments include chelating agents and/or zinc. We characterized real-world US treatment patterns in patients with WD.

Methods

This retrospective, observational medical chart review utilized deidentified clinical data, including treatment patterns, abstracted from patient medical charts between 01/2012 and 06/2017. Line of therapy was assessed based on disease presentation and aggregated. Index treatment was defined as the first line of therapy, followed by second line of therapy and third line of therapy. Results were summarized using descriptive statistics.

Results

A total of 225 patients were included (mean [SD] age at diagnosis: 24.7 [9.8] years). Initial disease presentation was both neurologic/psychiatric and hepatic in 52.9%, followed by neurologic/psychiatric (20.0%), hepatic (16.9%), and asymptomatic (10.2%). Median (first and third quartiles) duration of follow-up from diagnosis was 39.5 (33.8–60.4) months. The most common first line of therapy was penicillamine monotherapy in 45.5%, followed by trientine monotherapy (26.1%) and chelator/zinc combination therapy (21.2%). A total of 167/222 (75.2%) patients remained on first line of therapy during the follow-up period. Of the 13.5% who switched to second line of therapy, most changed to trientine monotherapy (53.3%). All those who switched to third line of therapy transitioned to zinc monotherapy (100.0%). Unexpectedly, 11.3% discontinued first line of therapy without transitioning to a subsequent therapy. The primary rationale for index monotherapy selection was improved efficacy (61.6%). Most discontinuations were due to side effects/tolerability (40.8%). Treatment patterns varied by initial disease presentation, practice setting, physician specialty, and geographic location.

Conclusion

These results demonstrate a lack of consensus in the US regarding first-line treatment for patients with WD. Evidence-based treatment pathways informed by high-quality clinical trials for improved health outcomes are needed.
Exclusion and the growth of AI technology: a trade-theoretic analysis
Authors: Hazari Bharat , Mohan Vijay
Published: May 2024

This study provides a four-good general equilibrium framework with international trade for assessing the impact of the advancement of automation and artificial intelligence (A&AI) on the welfare of a group of agents who are excluded from both owning productive assets, such as capital and land, as well as consuming digital output (digital exclusion). We show that, depending on the magnitude of the factor intensities, the accumulation of A&AI capital may negatively affect the income of the excluded group, who provide unskilled labor, or the owners of land. In doing so, we bring out the conflict of interests that may arise between the owners of A&AI capital and other groups within society, which has implications for the pressure that exists to slow down the adoption of A&AI in an economy.
Association of specific ACE2 and TMPRSS2 variants with circulatory cytokines of COVID-19 Emirati patients
Authors: Elemam Noha M. , Bouzid Amal , Alsafar Habiba , Ahmed Samrein BM , Hafezi Shirin , Venkatachalam Thenmozhi , Eldohaji Leen , Al Hamidi Tasneem , Gerges Peter Habib , Halabi Nour , Hadj-Kacem Hassen , Talaat Iman M. , Taneera Jalal , Sulaiman Nabil , Maghazachi Azzam A. , Hamid Qutayba , Hamoudi Rifat , Saber-Ayad Maha
Published: May 2024

Introduction

The COVID-19 pandemic represented one of the most significant challenges to researchers and healthcare providers. Several factors determine the disease severity, whereas none alone can explain the tremendous variability. The Single nucleotide variants (SNVs) in angiotensin-converting enzyme-2 (ACE2) and transmembrane serine protease type-2 (TMPRSS2) genes affect the virus entry and are considered possible risk factors for COVID-19.

Methods

We compiled a panel of gene variants from both genes and used in-silico analysis to predict their significance. We performed biological validation to assess their capacity to alter the ACE2 interaction with the virus spike protein. Subsequently, we conducted a retrospective comparative genome analysis on those variants in the Emirati patients with different disease severity (total of 96) along with 69 healthy control subjects.

Results

Our results showed that the Emirati population lacks the variants that were previously reported as associated with disease severity, whereas a new variant in ACE2 “Chr X:g.15584534” was associated with disease severity specifically among female patients. In-silico analysis revealed that the new variant can determine the ACE2 gene transcription. Several cytokines (GM-CSF and IL-6) and chemokines (MCP-1/CCL2, IL-8/CXCL8, and IP-10/CXCL10) were markedly increased in COVID-19 patients with a significant correlation with disease severity. The newly reported genetic variant of ACE2 showed a positive correlation with CD40L, IL-1β, IL-2, IL-15, and IL-17A in COVID-19 patients.

Conclusion

Whereas COVID-19 represents now a past pandemic, our study underscores the importance of genetic factors specific to a population, which can influence both the susceptibility to viral infections and the level of severity; subsequently expected required preparedness in different areas of the world.
Evaluation of the causal effects of immune cells on ischemic stroke: a Mendelian randomization study
Authors: Wang Kunyu , Zhang Beilin , Li Min , Duan Hanying , Jiang Zhuoya , Gao Su , Chen Jing , Fang Shaokuan
Published: May 2024

Background

Ischemic stroke (IS) is a cerebrovascular disease caused by various factors, and its etiology remains inadequately understood. The role of immune system dysfunction in IS has been increasingly recognized. Our objective was to evaluate whether circulating immune cells causally impact IS risk.

Methods

We conducted two-sample Mendelian randomization analyses to evaluate the causal effects of 731 immune cell traits on IS, utilizing publicly available genome-wide association studies (GWAS) summary statistics for 731 immune cell traits as exposure data, and two GWAS statistics for IS as outcome data. A set of sensitivity analyses, including Cochran’s Q test, I2 statistics, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out sensitivity analyses, were performed to assess the robustness of the results. Additionally, meta-analyses were conducted to combine the results from the two different IS datasets. Finally, we extracted instrumental variables of immune cell traits with causal effects on IS in both IS datasets for SNP annotation.

Results

A total of 41 and 35 immune cell traits were identified to have significant causal effects on IS based on two different IS datasets, respectively. Among them, the immune cell trait CD62L- plasmacytoid Dendritic Cell AC and CD4+ CD8dim T cell%leukocyte respectively served as risk factor and protective element in both IS datasets. The robustness of the causal effects was confirmed through the sensitivity analyses. The results of the meta-analyses further support the causal effects of CD62L- plasmacytoid Dendritic Cell AC (pooled OR=1.030, 95%CI: 1.011–1.049, P=0.002) and CD4+ CD8dim T cell%leukocyte (pooled OR=0.959, 95%CI: 0.935–0.984, P=0.001). Based on these two immune cell traits, 33 genes that may be related to the causal effects were mapped.

Conclusions

Our study demonstrated the potential causal effects of circulating immune cells on IS, providing valuable insights for future studies aimed at preventing IS.
Cost-effectiveness of treating relapsed or refractory 3L+ follicular lymphoma with axicabtagene ciloleucel vs mosunetuzumab in the United States
Authors: Oluwole Olalekan O. , Ray Markqayne D. , Zur Richard M. , Ferrufino Cheryl P. , Doble Brett , Patel Anik R. , Bilir S. Pinar
Published: May 2024

Introduction

Novel therapies for 3L+ relapsed/refractory (r/r) follicular lymphoma (FL) have been approved recently by the US Food and Drug Administration including anti-CD19 CAR-T therapies such as axicabtagene ciloleucel (axi-cel) and CD20 × CD3 T-cell-engaging bispecific monoclonal antibodies such as mosunetuzumab (mosun). The objective of this study was to assess the cost-effectiveness of axi-cel compared to mosun in 3L+ r/r FL patients from a US third-party payer perspective.

Methods

A three-state (progression-free, progressed disease, and death) partitioned-survival model was used to compare two treatments over a lifetime horizon in a hypothetical cohort of US adults (age ≥18) receiving 3L+ treatment for r/r FL. ZUMA-5 and GO29781 trial data were used to inform progression-free survival (PFS) and overall survival (OS). Mosun survival was modeled via hazard ratios (HRs) applied to axi-cel survival curves. The PFS HR value was estimated via a matching-adjusted indirect comparison (MAIC) based on mosun pseudo-individual patient data and adjusted axi-cel data to account for trial populations differences. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analyses (PSA) were conducted. Scenario analyses included: 1) the mosun HRs were applied to the weighted (adjusted) ZUMA-5 24-month data to most exactly reflect the MAIC, 2) mosun HR values were applied to axi-cel 48-month follow-up data, and 3) recent axi-cel health state utility values in diffuse large B-cell lymphoma patients.

Results

The analysis estimated increases of 1.82 LY and 1.89 QALY for axi-cel compared to mosun. PFS for axi-cel patients was 6.42 LY vs. 1.60 LY for mosun. Increase of $257,113 in the progression-free state was driven by one-time axi-cel treatment costs. Total incremental costs for axi-cel were $204,377, resulting in an ICER of $108,307/QALY gained. The OWSA led to ICERs ranging from $240,255 to $75,624, with all but two parameters falling below $150,000/QALY. In the PSA, axi-cel had an 64% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively.

Discussion

This study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.
Immunomodulation by glucocorticoid-induced leucine zipper in macrophages: enhanced phagocytosis, protection from pyroptosis, and altered mitochondrial function
Authors: Legroux Thierry M. , Schymik Hanna S. , Gasparoni Gilles , Mohammadi Saeed , Walter Jörn , Libert Claude , Diesel Britta , Hoppstädter Jessica , Kiemer Alexandra K.
Published: May 2024

Glucocorticoids, which have long served as fundamental therapeutics for diverse inflammatory conditions, are still widely used, despite associated side effects limiting their long-term use. Among their key mediators is glucocorticoid-induced leucine zipper (GILZ), recognized for its anti-inflammatory and immunosuppressive properties. Here, we explore the immunomodulatory effects of GILZ in macrophages through transcriptomic analysis and functional assays. Bulk RNA sequencing of GILZ knockout and GILZ-overexpressing macrophages revealed significant alterations in gene expression profiles, particularly impacting pathways associated with the inflammatory response, phagocytosis, cell death, mitochondrial function, and extracellular structure organization activity. GILZ-overexpression enhances phagocytic and antibacterial activity against Salmonella typhimurium and Escherichia coli, potentially mediated by increased nitric oxide production. In addition, GILZ protects macrophages from pyroptotic cell death, as indicated by a reduced production of reactive oxygen species (ROS) in GILZ transgenic macrophages. In contrast, GILZ KO macrophages produced more ROS, suggesting a regulatory role of GILZ in ROS-dependent pathways. Additionally, GILZ overexpression leads to decreased mitochondrial respiration and heightened matrix metalloproteinase activity, suggesting its involvement in tissue remodeling processes. These findings underscore the multifaceted role of GILZ in modulating macrophage functions and its potential as a therapeutic target for inflammatory disorders, offering insights into the development of novel therapeutic strategies aimed at optimizing the benefits of glucocorticoid therapy while minimizing adverse effects.
Serum ASGR2 level: an efficacy biomarker for balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension
Authors: Xu Wei-Jie , Wang Shang , Zhao Qian-Hao , Xu Jia-Yi , Hu Xiao-Yi , Gong Su-Gang , He Jing , Qiu Hong-Ling , Luo Ci-Jun , Xu Jian , Li Hui-Ting , Li Ze-Pu , Wang Lan , Shi Yu , Zhao Ya-Lin , Jiang Rong
Published: May 2024

Background

This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Methods

Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters.

Results

Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05).

Conclusion

Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.
A qualitative assessment of community perceptions and practices towards schistosomiasis prior to introduction of a potential novel treatment option for preschool-age children in Kenya
Authors: Masaku Janet , Gachohi John M. , Sinkeet Alice , Maghanga Mary , Wakesho Florence , Omondi Wyckliff , Reigl Lisa Sophie , Lange Isabelle L. , Winkler Andrea S. , Njenga Sammy M. , Amuyunzu-Nyamongo Mary
Published: May 2024

Background

Over 50 million preschool-age children (PSAC) in Africa need treatment for schistosomiasis but are excluded due to lack of a suitable child-friendly medication. The Paediatric Praziquantel Consortium has developed a novel paediatric formulation for PSAC. In advance of its roll-out, we conducted a social science study to draw lessons to inform implementation.

Methods

We conducted a cross-sectional study in eight villages in two purposively selected highly endemic Kenyan counties (Homa Bay and Kwale). We conducted 17 in-depth interviews with community opinion leaders and 21 with parents/guardians of PSAC. Twelve focus group discussions with parents/guardians of PSAC were also held. The aim was to assess their knowledge, perceptions, practices and willingness to participate in the medication’s roll-out for schistosomiasis. Thematic data analysis was performed.

Results

Most participants had heard of schistosomiasis and perceived it to be a serious disease whose treatment should be prioritised. Others felt it was a common disease that should not cause concern. Some people believed schistosomiasis was caused by witchcraft while others regarded it as a sexually transmitted infection. In addition, some practices like poor human waste disposal and water contact were thought to contribute to continued transmission of the disease.

Conclusion

Community members know and perceive schistosomiasis to be serious, but misinformation about its cause is prevalent. The study suggests the need for increased awareness creation to change the perceptions of communities in relation to schistosomiasis prevention and control. Community sensitisation should be prioritised in advance of medication roll-out.
Inhibition of TRPA1-like alleviated unfolded protein response and apoptosis by regulating cytoplasmic Ca2+ in Yesso scallop Patinopecten yessoensis under high temperature stress
Authors: Ma Xiaoxue , Gu Wenfei , Yang Chuanyan , He Zhaoyu , Fan Hongmei , Wang Lingling , Song Linsheng
Published: May 2024

Transient receptor potential ankyrin subtype 1 (TRPA1) is a nonselective cation channel protein typically forms ion channels that regulate intracellular calcium homeostasis, and can be induced by temperature and various chemicals. In the present study, the involvement of PyTRPA1-like in regulating unfolded protein response (UPR) and apoptosis in Yesso Scallop Patinopecten yessoensis under high temperature stress was investigated. The mRNA transcripts of PyTRPA1-like were detected in haemocytes and all the examined tissues with the highest expression level in mantle. After TRPA1 activator (allyl-isothiocyanate, AITC) and high temperature (25°C) treatment, the expression level of PyTRPA1-like mRNA and the Ca2+ content in haemocytes increased significantly (p < 0.05) at 3 h, and then recovered to the normal level at 12 h, and the expression level of PyGRP78, PyIRE1, PyATF6β, PyPERK and PyCaspase-3 mRNA in haemocytes, and Caspase-3 activity and apoptosis rate were also significantly upregulated (p < 0.05). After TRPA1 antagonist (HC-030031) and high temperature (25°C) treatment, the intracellular Ca2+ content, the transcripts of PyGRP78, PyIRE1 and PyCaspase-3 in haemocytes, as well as the Caspase-3 activity and apoptosis rate decreased significantly compared to the control group (p < 0.05), while the Ca2+ distribution in haemocytes showed no difference with that in control group. These results collectively suggest that PyTRPA1-like plays important roles in regulating UPR and apoptosis by mediating calcium influx under high temperature stress in scallop P. yessoensis.
Efficacy and safety of topical clobetasol propionate in comparison with alternative treatments in oral lichen planus: an updated systematic review and meta-analysis
Authors: Zheng Tao , Liu ChengYong , Wang YeTong , Zhou Rong , Wu Dan , Tan Jin , Zhu KeKe
Published: May 2024

Background

Oral lichen planus (OLP) is a relatively common chronic T cell-mediated disease characterized by pain and inflammation. Clobetasol propionate (CLO) is the first-line drug in the treatment of OLP. The meta-analysis aimed to evaluate the efficacy and safety of CLO for treating patients with OLP.

Methods

PubMed, Embase and Web of Science were systematically searched from the database inception date up to August 2023. There were no restrictions on language or date of publication. The outcomes of our interest were as follows: improvement of clinical signs and/or symptoms, total lesion size, relapse and adverse events.

Results

A total of 17 RCTs evaluating the effects of CLO were included in this study. The results revealed no significant difference in the clinical score (WMD = 0.14, 95% CI: −0.39, 0.66; p = 0.609) and pain score (WMD = 0.17, 95% CI: −0.44, 0.79; p = 0.582) between CLO and other treatments. However, clinical resolution (RR = 1.61, 95% CI: 1.17, 2.22; p = 0.003) and symptoms improvement (RR = 1.80, 95% CI: 1.17, 2.77; p = 0.008) were significantly different between CLO and other treatments. Moreover, there was a significant reduction in the total lesion size with CLO treatment (WMD = -0.58, 95% CI: −1.03, −0.13; p = 0.011). In addition, CLO showed no statistical incidence of adverse events (RR = 1.46, 95% CI: 0.86, 2.50; p = 0.161) and relapse (RR = 1.56, 95% CI: 0.66, 3.71; p = 0.314) than other therapies.

Conclusion

This systematic review and meta-analysis of 17 randomized clinical trials supported the long-term application of CLO as an effective regimen in OLP patients.
The prognostic value of Dickkopf-3 (Dkk3), TGFB1 and ECM-1 in prostate cancer
Authors: Al Shareef Zainab , Hachim Mahmood Y. , Bouzid Amal , Talaat Iman M. , Al-Rawi Natheer , Hamoudi Rifat , Hachim Ibrahim Y.
Published: May 2024

Prostate cancer (PCa) is considered one of the most common cancers worldwide. Despite advances in patient diagnosis, management, and risk stratification, 10%–20% of patients progress to castration-resistant disease. Our previous report highlighted a protective role of Dickkopf-3 (DKK3) in PCa stroma. This role was proposed to be mediated through opposing extracellular matrix protein 1 (ECM-1) and TGF-β signalling activity. However, a detailed analysis of the prognostic value of DKK3, ECM-1 and members of the TGF-β signalling pathway in PCa was not thoroughly investigated. In this study, we explored the prognostic value of DKK3, ECM-1 and TGFB1 using a bioinformatical approach through analysis of large publicly available datasets from The Cancer Genome Atlas Program (TGCA) and Pan-Cancer Atlas databases. Our results showed a significant gradual loss of DKK3 expression with PCa progression (p < 0.0001) associated with increased DNA methylation in its promoter region (p < 1.63E-12). In contrast, patients with metastatic lesions showed significantly higher levels of TGFB1 expression compared to primary tumours (p < 0.00001). Our results also showed a marginal association between more advanced tumour stage presented as positive lymph node involvement and low DKK3 mRNA expression (p = 0.082). However, while ECM1 showed no association with tumour stage (p = 0.773), high TGFB1 expression showed a significant association with more advanced stage presented as advanced T3 stage compared to patients with low TGFB1 mRNA expression (p < 0.001). Interestingly, while ECM1 showed no significant association with patient outcome, patients with high DKK3 mRNA expression showed a significant association with favourable outcomes presented as prolonged disease-specific (p = 0.0266), progression-free survival (p = 0.047) and disease-free (p = 0.05). In contrast, high TGFB1 mRNA expression showed a significant association with poor patient outcomes presented as shortened progression-free (p = 0.00032) and disease-free survival (p = 0.0433). Moreover, DKK3, TGFB1 and ECM1 have acted as immune-associated genes in the PCa tumour microenvironment. In conclusion, our findings showed a distinct prognostic value for this three-gene signature in PCa. While both DKK3 and TGFB1 showed a potential role as a clinical marker for PCa stratification, ECM1 showed no significant association with the majority of clinicopathological parameters, which reduce its clinical significance as a reliable prognostic marker.