bluuebunny/crossref_metadata_2025 huggingface dataset:
SEJARAH MITIGASI BENCANA ERUPSI DI LERENG TIMUR GUNUNG KELUD, 2008-2015
Authors: Rohmah Utia Binti Yuhanni'ur , Ridhoi Ronald
Published: August 2024

The eruption of Mount Kelud in 2014 showed deviations in eruption characteristics and unpredictability of lava flow direction, and the most severely affected locations were due to volcanic materials. The incident led to the analysis of the eruption and disaster mitigation on the eastern slope of Mount Kelud. In the preparatory process, the authors used a material environmental history approach, integrating Bankoff’s concept of co-volcanic societies and the community’s perception of living harmoniously with hazards in Pandansari Village. This study applied historical research methods, including topic selection, heuristics, source criticism, interpretation, and historiography. The data sources were activity reports, newspapers, photos, maps, and interviews. Findings revealed that the 2014 eruption of Gunung Kelud had a significant impact on Pandansari Village, damaging infrastructures and agricultural land. In addition, this study highlighted the subsequent development of a more systematic disaster mitigation approach implemented by the local community and government in response to the threat of volcanic eruptions.
Countering the Western Canon: Other Ways of Knowing about Journalism and Media
Authors: Masri Mohd Shazani
Published: August 2024

A book review on "Countering the Western Canon: Other Ways of Knowing about Journalism and Media" by Ahmad Murad Merican.
Burnout Among Critical Care Respiratory Therapists A Cross-Sectional Study
Authors: Patterson Shawn
Published: August 2024

Background: This study aims to investigate burnout among critical care respiratory therapists. Burnout syndrome, characterized by fatigue, cynicism, and reduced professional efficacy, is prevalent in high-stress careers such as healthcare. While extensive research has examined burnout among physicians and nurses, there needs to be more understanding of its prevalence and impact among respiratory therapists in critical care settings. This cross-sectional study seeks to fill this gap and provide insights into the burnout experienced by this specific healthcare professional group. Methods: The study used a cross-sectional design, a survey approach was used to gather data, and the research focused on assessing the presence of burnout and burnout syndrome (BOS) among critical care respiratory therapists. The participants were critical care respiratory therapists working in healthcare settings. This method allowed for the collection of information on the prevalence of burnout in this specific healthcare clinician group. The survey-based approach provided a practical and efficient method for examining the impact of burnout on critical care respiratory therapists. Results: The study examined burnout levels among 591 respiratory therapists (RCPs) and found high levels of emotional exhaustion (EE) with an average score of 32.85 and depersonalization (DP) with an average score of 12.28. These scores indicate high levels of burnout and correlate with the reported burnout level of 88.54%. These findings suggest that RCPs experience significant burnout, as noted in the Maslach Burnout Index (MBI) values, highlighting the need for interventions to address burnout in this specialized clinical group.
Overcoming treatment resistance in cholangiocarcinoma: current strategies, challenges, and prospects
Authors: Wang Jiayi , Liu Siyan , Cao Yi , Chen Yong
Published: August 2024

Significant advancements in our understanding and clinical treatment of cholangiocarcinoma (CCA) have been achieved over the past 5 years. Groundbreaking studies have illuminated the immune landscape and pathological characteristics of the tumor microenvironment in CCA. The development of immune- and metabolism-based classification systems has enabled a nuanced exploration of the tumor microenvironment and the origins of CCA, facilitating a detailed understanding of tumor progression modulation. Despite these insights, targeted therapies have not yet yielded satisfactory clinical results, highlighting the urgent need for innovative therapeutic strategies. This review delineates the complexity and heterogeneity of CCA, examines the current landscape of therapeutic strategies and clinical trials, and delves into the resistance mechanisms underlying targeted therapies. Finally, from a single-cell and spatial transcriptomic perspective, we address the challenge of therapy resistance, discussing emerging mechanisms and potential strategies to overcome this barrier and enhance treatment efficacy.
Three-dimensional cell culture conditions promoted the Mesenchymal-Amoeboid Transition in the Triple-Negative Breast Cancer cell line MDA-MB-231
Authors: Rodríguez-Cruz Daniela , Boquet-Pujadas Aleix , López-Muñoz Eunice , Rincón-Heredia Ruth , Paredes-Díaz Rodolfo , Flores-Fortis Mauricio , Olivo-Marin Jean-Christophe , Guillén Nancy , Aguilar-Rojas Arturo
Published: August 2024

Introduction

Breast cancer (BC) is the leading cause of death among women, primarily due to its potential for metastasis. As BC progresses, the extracellular matrix (ECM) produces more type-I collagen, resulting in increased stiffness. This alteration influences cellular behaviors such as migration, invasion, and metastasis. Specifically, cancer cells undergo changes in gene expression that initially promote an epithelial-to-mesenchymal transition (EMT) and subsequently, a transition from a mesenchymal to an amoeboid (MAT) migration mode. In this way, cancer cells can migrate more easily through the stiffer microenvironment. Despite their importance, understanding MATs remains challenging due to the difficulty of replicating in vitro the conditions for cell migration that are observed in vivo.

Methods

To address this challenge, we developed a three-dimensional (3D) growth system that replicates the different matrix properties observed during the progression of a breast tumor. We used this model to study the migration and invasion of the Triple-Negative BC (TNBC) cell line MDA-MB-231, which is particularly subject to metastasis.

Results

Our results indicate that denser collagen matrices present a reduction in porosity, collagen fiber size, and collagen fiber orientation, which are associated with the transition of cells to a rounder morphology with bleb-like protrusions. We quantified how this transition is associated with a more persistent migration, an enhanced invasion capacity, and a reduced secretion of matrix metalloproteinases.

Discussion

Our findings suggest that the proposed 3D growth conditions (especially those with high collagen concentrations) mimic key features of MATs, providing a new platform to study the physiology of migratory transitions and their role in BC progression.
Numerical evaluation of methanol synthesis in catalytic wall-coated microreactors: scale-up and performance analysis of planar and monolithic designs
Authors: Silva João Lameu da , Santana Harrson Silva , Hodapp Maximilian Joachim
Published: August 2024

Methanol is one of the most important primary chemical compounds, being an interesting alternative for portable energy applications and also acting as a molecular platform for the synthesis of a wide range of commodities and high-added-value products. Traditionally, methanol is obtained by catalytic hydrogenation using synthesis gas (CO/CO2/H2) in fixed-bed reactors (FBRs), which require large reaction volumes and are limited by heat and mass transfer. Wall-coated microreactor technology (MRT) offers a promising alternative to traditional fixed-bed reactors. Despite their potential, industrial-scale adoption of microreactors faces challenges related to scale-up. This article aimed to assess methanol synthesis in wall-coated microreactors (planar, or MRP, and monolithic, or MRM) through numerical performance evaluation, using a fixed-bed reactor as a reference. A pre-analysis of carbon conversion into methanol from experimental data provided insightful conclusions about recommended operating parameters, suggested as 50 bar, 250°C, a CO2 ratio of 0.3–0.4, a gas hourly space velocity (GHSV) of 6,000–8,000 mL/g.h, and a stoichiometric hydrogen/carbon ratio of 2–4. The numerical model, coupling chemical kinetics into fluid dynamics, demonstrated good agreement with experimental data. Subsequently, a design of experiments identified optimal operating conditions for methanol synthesis (250°C, 50 bar, CO2 ratio = 0.32, GHSV = 7,595 mL/g.h, hydrogen/carbon ratio = 2.4) in an FBR. The MRP and MRM presented equivalent performance with the FBR after adjusting the surface catalytic loading. In particular, the MRP showed a potential feature for scale-up due to the decreased pressure drop. A reactor block with 10 parallelized channels was designed and evaluated by changing GHSV between 5,000 and 50,000 mL/g.h and varying surface catalytic loading from 0.04 to 0.12 kg/m2. Despite the formation of recirculation zones in the conical region, the flow distribution remained satisfactory, ensuring virtually uniform methanol production among units, providing increased operational flow, and maintaining the microscale efficiency with a relatively low pressure drop. The present article provides a comprehensive analysis of the fundamental interplay between kinetic effects, mass transfer phenomena, and reactor design in methanol synthesis by applying MRT concepts, offering important insights for performance optimization and scale-up of wall-coated microreactors.
Risk estimation for recurrent cardiovascular events using the SMART-REACH model and direct inpatient cost profiling in Indonesian ASCVD patients: a large-scale multicenter study
Authors: Dwiputra Bambang , Desandri Dwita Rian , Hartopo Anggoro Budi , Juzar Dafsah Arifa , Alkatiri Amir Aziz , Zuhdi Naufal , Ramadhan Putra Andito , Kenconosari Bernadhet Daisy , Phowira Jason , Widyantoro Bambang
Published: August 2024

Introduction

With atherosclerotic cardiovascular disease (ASCVD) cases increasing in Indonesia, there is a growing need to identify high-risk patients for recurrent cardiovascular events. Risk stratification could guide optimal secondary preventive therapy. Understanding the ASCVD direct inpatient costs could further provide insight in reducing the economic burden that comes with Indonesia's high number ASCVD cases. However, there is a significant gap in Indonesian large-scale research on both of these valuable data. Employing the SMART-REACH model, we can profile the risk of recurrent cardiovascular events in Indonesian ASCVD patients.

Objectives

Utilize the SMART-REACH model to estimate 10-year and lifetime risk of cardiovascular events in Indonesian ASCVD patients and describe the direct inpatient cost of ASCVD.

Methods

This descriptive cross-sectional study gathered data from 3,209 ASCVD patients aged 45–80 from two major cardiovascular centers using purposive sampling. Participants were patients admitted between January 2020 and March 2023 with ST-elevated myocardial infarct (STEMI), non-ST-elevated myocardial infarct (NSTEMI), and chronic coronary syndrome (CCS) requiring elective percutaneous coronary intervention (PCI). The SMART-REACH risk estimation model required clinical data upon admission, laboratory results within the first 24 h of admission, and cardiovascular medication prescribed upon discharge. The SMART-REACH model is a Fine and Gray competing risk model incorporating cardiovascular risk factors that estimates individual 10-year and lifetime risk for recurrent cardiovascular events which includes myocardial infarction, stroke, or vascular death. Direct inpatient cost profiling totaled all medical expenses incurred from ASCVD diagnosis admission to discharge. Results were reported descriptively with subgroup analyses.

Results

The cohorts (mean age 60.15 ± 8.6 years) were predominantly male [n = 2,537 (79.1%)], hypertensive [n = 2,267 (70.6%)], and diagnosed with STEMI [n = 1,732 (54%)]. The SMART-REACH model calculated a mean 10-year risk of 30.2% (95% CI 29.7–30.6) and a lifetime risk of 62.5% (95% CI 62.1–62.9). The direct inpatient cost of ASCVD patients includes a median 3,033 USD, with highest median costs in the STEMI subgroup (3,270 USD).

Conclusions

A significant number of Indonesian ASCVD patients exhibited notably high 10-year and lifetime risks of experiencing a major cardiovascular event. Combined with the direct inpatient cost, therapy optimization is crucially needed to mitigate these risks and further cost burden.
Mathematical modelling for gravity waves interactions coupled with localized water vapor and ozone in the atmosphere
Authors: Almohaimeed Ahmed S.
Published: August 2024

In the atmosphere, the interrelationship between dynamics and chemistry results in mutual influence and interaction. The behavior of internal gravity waves is influenced by the thermal effects caused by chemical components present in the atmosphere. In this investigation, the equations determining gravity waves are coupled with those characterizing the behavior of ozone and water vapor. To investigate the coupled equations, numerical analyses are conducted, and the resulting numerical results are presented. Internal gravity waves have been observed to influence the distribution of ozone and water vapor within the Earth’s atmosphere. It has been demonstrated, based on our findings, that wave fluctuations play a significant role in exerting a substantial effect. In addition, it has been observed that the influence of ozone and water vapor-induced heating on gravity waves is significant, particularly near the critical level where the mean flow induced by gravity waves plays a significant role.
Investigating mechanical and inflammatory pathological mechanisms in osteoarthritis using MSC-derived osteocyte-like cells in 3D
Authors: Gilbert Sophie J. , Jones Ryan , Egan Ben J. , Bonnet Cleo Selina , Evans Sam L. , Mason Deborah J.
Published: August 2024

Introduction

Changes to bone physiology play a central role in the development of osteoarthritis with the mechanosensing osteocyte releasing factors that drive disease progression. This study developed a humanised in vitro model to detect osteocyte responses to either interleukin-6, a driver of degeneration and bone remodelling in animal and human joint injury, or mechanical loading, to mimic osteoarthritis stimuli in joints.

Methods

Human MSC cells (Y201) were differentiated in 3-dimensional type I collagen gels in osteogenic media and osteocyte phenotype assessed by RTqPCR and immunostaining. Gels were subjected to a single pathophysiological load or stimulated with interleukin-6 with unloaded or unstimulated cells as controls. RNA was extracted 1-hour post-load and assessed by RNAseq. Markers of pain, bone remodelling, and inflammation were quantified by RT-qPCR and ELISA.

Results

Y201 cells embedded within 3D collagen gels assumed dendritic morphology and expressed mature osteocytes markers. Mechanical loading of the osteocyte model regulated 7564 genes (Padj p<0.05, 3026 down, 4538 up). 93% of the osteocyte transcriptome signature was expressed in the model with 38% of these genes mechanically regulated. Mechanically loaded osteocytes regulated 26% of gene ontology pathways linked to OA pain, 40% reflecting bone remodelling and 27% representing inflammation. Load regulated genes associated with osteopetrosis, osteoporosis and osteoarthritis. 42% of effector genes in a genome-wide association study meta-analysis were mechanically regulated by osteocytes with 10 genes representing potential druggable targets. Interleukin-6 stimulation of osteocytes at concentrations reported in human synovial fluids from patients with OA or following knee injury, regulated similar readouts to mechanical loading including markers of pain, bone remodelling, and inflammation.

Discussion

We have developed a reproducible model of human osteocyte like cells that express >90% of the genes in the osteocyte transcriptome signature. Mechanical loading and inflammatory stimulation regulated genes and proteins implicated in osteoarthritis symptoms of pain as well as inflammation and degeneration underlying disease progression. Nearly half of the genes classified as ‘effectors’ in GWAS were mechanically regulated in this model. This model will be useful in identifying new mechanisms underlying bone and joint pathologies and testing drugs targeting those mechanisms.
Mixing nuclear and conventional fossil fuel units within the baseload of PP using the CPLEX Optimizer
Authors: Al-Qahtani Abdullah M. , Al-Shaalan Abdullah M. , Al-Masry Waheed A. , Hussein Farh Hassan M.
Published: August 2024

The future electric loads in the Kingdom of Saudi Arabia (KSA) are increasing significantly, particularly in the Eastern Province of the KSA. These high-rise loads are primarily driven by the operational needs of the Saudi Arabian oil company Aramco, including oil refineries, and the infrastructures of the Saudi Basic Industries Corporation (SABIC) factories. This study aims to construct a nuclear power plant in that area to supplement and support the baseload currently covered by conventional generation units powered by fossil fuels within the Saudi Electricity Company (SEC) operations. The objective function is to minimize the operational costs of the power systems to the greatest extent possible. This paper describes a case study conducted using the IBM CPLEX Optimizer software to compare the operational costs of KSA’s power systems for a 24-h period. Two scenarios were considered and addressed: the first scenario without the inclusion of a nuclear power plant (NPP) and the second scenario with the inclusion of the NPP. The unit commitment problem was modeled for both scenarios. The obtained results revealed that the second scenario, which involved the penetration of the NPP, offered an optimal economic solution for operating KSA’s power systems. By employing the CPLEX Optimizer software and analyzing the unit commitment problem, this study provides valuable insights into the economic advantages of integrating the NPP into the power systems of the Kingdom of Saudi Arabia. The NPP shows viability in terms of minimizing the operational costs to 32.10 $/MWh compared to the first scenario where the operational costs were 42.10 $/MWh and resulted in almost 24% reduction in operational costs. In addition, the NPP is deemed as an optimal technology to contribute to the net zero goal by 2060, where it can reduce the reliance on fossil fuel power plants and contribute to the reduction of CO2 emissions.
Epigenetic dysregulated long non-coding RNAs in renal cell carcinoma based on multi-omics data and their influence on target drugs sensibility
Authors: Wang Jiawei , Dou Pingnan , Sun Yunwen , Zheng Jie , Wu Guanwei , Liu Heqian , Tao Lingsong
Published: August 2024

Purpose

Epigenetic modifications play a crucial role in cancer development, and our study utilized public data to analyze which leads to the discovery of significant epigenetic abnormalities in lncRNAs, offering valuable insights into prognosis and treatment strategies for renal carcinoma.

Methods

Public data were obtained from the Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) database. The analysis of the online public data was all completed in R software.

Results

We discovered a great number of epigenetic abnormalities of lncRNA in renal cancer, which is achieved by comparing the following modification and methylation of histone region changes on the promoter and enhancer of lncRNA: H3K27ac, H3K4me1, H3K4me3. As a result, 12 specific epigenetic disorders of lncRNA genes in renal cancer were identified. Finally, based on this lncRNA, we investigated the prognosis of renal cancer samples, among which 8 lncRNA can be seen as markers of prognosis in renal cancer, which had great prediction ability for ccRCC prognosis. Meanwhile, high risk score may pose response better to axitinib and nilotinib, but not sorafenib or sunitinib. Beyond, we observed an elevated level of risk score in immunotherapy non-responders. Further, biological enrichment and immuno-infiltration analysis was conducted to investigate the fundamental differences between patients categorized as high or low risk.

Conclusion

Our research improves the understanding in the function of epigenetic dysregulated long non-coding RNAs in renal carcinoma.
Ethiopian women's tokophobia of childbirth and its predictors: a systematic review and meta-analysis
Authors: Assimamaw Nega Tezera , Gonete Almaz Tefera , Angaw Dessie Abebaw , Techane Masresha Asmare , Kelkay Mengistu Mekonnen , Terefe Bewuketu
Published: August 2024

Background

Fear of childbirth is recognized as a growing problem in developing countries, including Ethiopia. The impact of this fear on women's reproductive choices and decisions is significant. Therefore, the systematic review and meta-analysis will help to consolidate the existing research on childbirth-related fear in Ethiopia. Synthesizing the findings and providing a pooled prevalence estimate, can contribute to a better understanding of the scale of the problem in the country.

Objective

This systematic review and meta-analysis assessed the pooled prevalence of childbirth-related fear and its associated factors among pregnant mothers in Ethiopia.

Methods

PubMed, Google Scholar, and African Journals Online were searched for included articles. A weighted inverse-variance random-effects model was used to estimate the prevalence of childbirth-related fear. Variations in the pooled estimates of the prevalence were adjusted through subgroup analysis according to the specific region where the study was conducted. Funnel plot and Egger's regression test were used to check for publication bias. STATA version 14 statistical software was used for meta-analysis.

Results

A total of 2,015 pregnant mothers were included. The combined prevalence of fear of childbirth among pregnant mothers was found to be 21% (95% CI: 19–22; I2 = 0.00%, p value < 0.001). Based on the subgroup analysis, the prevalence of fear of childbirth among pregnant mothers was 24% in SNNPRs, 25% in Oromia, and 11% in Addis Ababa.

Conclusion

The findings of the meta-analysis indicating a high prevalence of fear of childbirth among pregnant mothers in Ethiopia and identifying associated risk factors highlight the importance of addressing this issue within the healthcare system. Integrating prevention-based services for mothers with childbirth fears into the antenatal care model could be a valuable approach to support women and mitigate the impact of fear on their reproductive experiences.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/#myprospero, identifier [CRD42023411103].
The granulocyte colony-stimulating factor produced during Streptococcus suis infection controls neutrophil recruitment in the blood without affecting bacterial clearance
Authors: Bleuzé Marêva , Lehoux Mélanie , Auger Jean-Philippe , Gottschalk Marcelo , Segura Mariela
Published: August 2024

Streptococcus suis causes diseases in pigs and has emerged as a zoonotic agent. When infected, the host develops an exacerbated inflammation that can lead to septic shock and meningitis. Although neutrophils greatly infiltrate the lesions, their dynamics during S. suis infection remain poorly described. Moreover, very few studies reported on the production and role of a key factor in the regulation of neutrophils: the colony-stimulating granulocyte factor (G-CSF). In this study, we characterized the G-CSF-neutrophil axis in the pathogenesis of S. suis induced disease. Using a mouse model of S. suis infection, we first evaluated the recruitment of neutrophils and their activation profile by flow cytometry. We found that infection provokes a massive neutrophil recruitment from the bone marrow to the blood and spleen. In both compartments, neutrophils displayed multiple activation markers. In parallel, we observed high systemic levels of G-CSF, with a peak of production coinciding with that of neutrophil recruitment. We then neutralized the effects of G-CSF and highlighted its role in the release of neutrophils from the bone marrow to the blood. However, it did not affect bacteremia nor the cytokine storm induced by S. suis. In conclusion, systemic G-CSF induces the release of neutrophils from the bone marrow to the blood, but its role in inflammation or bacterial clearance seems to be compensated by unknown factors. A better understanding of the role of neutrophils and inflammatory mediators could lead to better strategies for controlling the infection caused by S. suis.
Contribution of microglia/macrophage to the pathogenesis of TMEV infection in the central nervous system
Authors: Zhang Qianye , Sun Wei , Zheng Mingxiao , Zhang Ning
Published: August 2024

The infection of the central nervous system (CNS) with neurotropic viruses induces neuroinflammation and an immune response, which is associated with the development of neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). The activation of both innate and adaptive immune responses, involving microglia, macrophages, and T and B cells, while required for efficient viral control within the CNS, is also associated with neuropathology. Under pathological events, such as CNS viral infection, microglia/macrophage undergo a reactive response, leading to the infiltration of immune cells from the periphery into the brain, disrupting CNS homeostasis and contributing to the pathogenesis of disease. The Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelination disease (TMEV-IDD), which serves as a mouse model of MS. This murine model made significant contributions to our understanding of the pathophysiology of MS following subsequent to infection. Microglia/macrophages could be activated into two different states, classic activated state (M1 state) and alternative activated state (M2 state) during TMEV infection. M1 possesses the capacity to initiate inflammatory response and secretes pro-inflammatory cytokines, and M2-liked microglia/macrophages are anti-inflammatory characterized by the secretion of anti-inflammatory cytokines. This review aims to discuss the roles of microglia/macrophages M1/M2-liked polarization during TMEV infection, and explore the potential therapeutic effect of balancing M1/M2-liked polarization of microglia/macrophages on MS.
Senescence-related genes and proteins in the development of Alzheimer’s disease: evidence from transcriptomic and Mendelian randomization analysis
Authors: Liu Ying , Chen Jiao
Published: August 2024

Purpose

Alzheimer’s disease (AD) is a common neurodegenerative disease, which can lead to cognitive impairment and dementia. Since AD is tightly associated with aging and cellular senescence, objective of this study was to investigate the association between senescence-related genes and proteins (SRGs and SRPs) and the development of AD.

Design

The whole study was based on transcriptomic analysis of control and AD brain tissues and Mendelian randomization (MR) analysis.

Methods

For transcriptomic analysis, GSE5281 dataset from GEO database contains the transcriptomic data of human brain tissues (n = 161) from control group and AD patients. The expression of SRGs in control and AD brain tissues were compared by Student’s t test. For MR analysis, the instrumental single-nucleotide polymorphisms (SNPs) associated with 110 SRPs were filtered and selected from a large genome-wide association study (GWAS) for plasma proteome. The causality between plasma levels of SRPs and AD was explored using GWAS data of AD from Lambert et al. (17,008 cases and 37,154 controls) and further validated by using data from FinnGen consortium (6,489 patients and 170,489 controls). MR estimate was performed using the inverse-variance weighted (IVW) method and the heterogeneity and pleiotropy of results were tested.

Results

Transcriptomic analysis identified 36 up-regulated (including PLAUR) and 8 down-regulated SRGs in AD brain tissues. In addition, the MR results at both discovery and validation stages supported the causality between plasma levels of PLAUR (IVW-p = 3.04E-2, odds ratio [OR] = 1.15), CD55 (IVW-p = 1.56E-3, OR = 0.86), and SERPINE2 (IVW-p = 2.74E-2, OR = 0.91) and the risk of AD.

Conclusion

Our findings identified that PLAUR, as an SRG, may take part in the development of AD and found that high plasma levels of PLAUR was associated with increased risk of AD, indicating that this gene was a risk factor for this disease and providing the rationale of existing drugs or new preventative and therapeutic strategies.
Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
Authors: Xie Yijun , Xiao Di , Li Duo , Peng Mei , Peng Wei , Duan Huaxin , Yang Xiaoping
Published: August 2024

Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.
Fully-automated production of [68Ga]Ga-Trivehexin for clinical application and its biodistribution in healthy volunteers
Authors: Wang Binchen , Jiang Yaqun , Zhu Jiaxu , Wu Huiqin , Wu Jianyuan , Li Ling , Huang Jianying , Xiao Zhiwei , He Yong
Published: August 2024

Background

The αvβ6-integrin targeting trimeric ligand [68Ga]Ga-Trivehexin has emerged as a promising candidate for clinical application due to its clinical imaging potentials in various malignant cancers. Our objective was to develop a simplified and reproducible module-based automated synthesis protocol to expand its availability in clinical application.

Methods

The pH value and the precursor load of radiolabeling were explored using an iQS-TS fully-automated module. Radiochemical purity was evaluated by radio-HPLC and radio-TLC. The ethanol content, radionuclide purity and identity, bacterial endotoxins, sterility, and stability of the final product [68Ga]Ga-Trivehexin were all tested. Biodistribution of [68Ga]Ga-Trivehexin in healthy volunteers was also conducted.

Results

The synthesis was explored and established using fully-automated module with outstanding radiochemical purity (>99%). Considering molar activity and economic costs, a pH of 3.6 and precursor dose of 30 μg were determined to be optimal. All relevant quality control parameters were tested and met the requirement of European Pharmacopoeia. In vitro stability test and imaging in healthy volunteer indicated the practical significance in clinical routines.

Conclusions

A fully-automated synthesis protocol for [68Ga]Ga-Trivehexin using the iQS-TS synthesis module was achieved and conformed to the clinical quality standards.

Clinical trial registration

ClinicalTrials.gov, NCT05835570. Registered 28 April 2023, https://www.clinicaltrials.gov/study/NCT05835570.
Optimization of culture conditions for endophytic bacteria in mangrove plants and isolation and identification of bacteriocin
Authors: Peng Jinju , Xie Xingpeng , Fan Tingli , Ma Haotian , Li Yang , Luo Shuaishuai , Yu Mengbo , Ding Yuexia , Ma Yi
Published: August 2024

Introduction: The antibacterial protein PAG14 was extracted from a metabolite of Bacillus G14 isolated from mangrove plants.

Methods: In this study, Pseudomonas aeruginosa, Pasteurell multocide, Enterobacter aerogenes, and Enterococcus faecalis were used as indicator bacteria to screen endophytes that exhibited antibacterial activity. The endophyte culture conditions were optimized to enhance productivity. Subsequently, the culture supernatant was salted using ammonium sulfate, followed by purification using dextran gel chromatography and ion exchange column techniques. Finally, the structures of antibacterial proteins were identified using mass spectrometry.

Results and Discussion: The optimal culture conditions for Bacillus G14 were 2% mannitol, 0.5% fish peptone, 0.05% KH2PO4 + 0.05% K2HPO4 + 0.025% MnSO4·H2O. The antibacterial substances exhibited stability within the temperature range of 30–40°C and pH range of 5.0–7.0, while displaying sensitivity toward enzymes. The antibacterial activity decreased as the duration of UV irradiation increased. The antibacterial protein PAG14, isolated from the culture broth of Bacillus G14 through purification using dextran gel and ion-exchange columns, was identified as a class III bacteriocin using LC-MS/MS, similar to Lysozyme C. These findings serve as a theoretical foundation for the investigation and application of bacteriocins in food products.
Selective inhibitor of sodium-calcium exchanger, SEA0400, affects NMDA receptor currents and abolishes their calcium-dependent block by tricyclic antidepressants
Authors: Boikov Sergei I. , Karelina Tatiana V. , Sibarov Dmitry A. , Antonov Sergei M.
Published: August 2024

The open-channel block of N-methyl-D-aspartate receptors (NMDARs) and their calcium-dependent desensitization (CDD) represent conventional mechanisms of glutamatergic synapse regulation. In neurotrauma, neurodegeneration, and neuropathic pain the clinical benefits of cure with memantine, ketamine, Mg2+, and some tricyclic antidepressants are often attributed to NMDAR open-channel block, while possible involvement of NMDAR CDD in the therapy is not well established. Here the effects of selective high-affinity sodium-calcium exchanger (NCX) isoform 1 inhibitor, SEA0400, on NMDA-activated whole-cell currents and their block by amitriptyline, desipramine and clomipramine recorded by patch-clamp technique in cortical neurons of primary culture were studied. We demonstrated that in the presence of extracellular Ca2+, 50 nM SEA0400 caused a reversible decrease of the steady-state amplitude of NMDAR currents, whereas loading neurons with BAPTA or the removal of extracellular Ca2+ abolished the effect. The decrease did not exceed 30% of the amplitude and did not depend on membrane voltage. The external Mg2+ block and 50 nM SEA0400 inhibition of currents were additive, suggesting their independent modes of action. In the presence of Ca2+ SEA0400 speeded up the decay of NMDAR currents to the steady state determined by CDD. The measured IC50 value of 27 nM for SEA0400-induced inhibition coincides with that for NCX1. Presumably, SEA0400 effects are induced by an enhancement of NMDAR CDD through the inhibition of Ca2+ extrusion by NCX1. SEA0400, in addition, at nanomolar concentrations could interfere with Ca2+-dependent effect of tricyclic antidepressants. In the presence of 50 nM SEA0400, the IC50s for NMDAR inhibition by amitriptyline and desipramine increased by about 20 folds, as the Ca2+-dependent NMDAR inhibition disappeared. This observation highlights NCX1 involvement in amitriptyline and desipramine effects on NMDARs and unmasks competitive relationships between SEA0400 and these antidepressants. Neither amitriptyline nor desipramine could affect NCX3. The open-channel block of NMDARs by these substances was not affected by SEA0400. In agreement, SEA0400 did not change the IC50 for clomipramine, which acts as a pure NMDAR open-channel blocker. Thus, NCX seems to represent a promising molecular target to treat neurological disorders, because of the ability to modulate NMDARs by decreasing the open probability through the enhancement of their CDD.
Research on the identification method of cable insulation defects based on Markov transition fields and transformer networks
Authors: Zhao Ning , Fang Yongyi , Wang Siying , Li Qian , Wang Xiaonan , Feng Chi
Published: August 2024

Identifying cable insulation defects is crucial for preventing system failures and ensuring the reliability of electrical infrastructure. This paper introduces a novel method leveraging the Markov transition field (MTF) and Transformer network to improve the precision of cable insulation defect identification and enhance the algorithm's noise resistance. Firstly, the algorithm performs modal transformation on the time series data acquired by the ultrasonic probe through MTF, generating corresponding images. Following this, the image data are input into a pre-trained Transformer network to achieve automated feature extraction. Subsequently, a multi-head attention mechanism is introduced, which assigns weights to the features extracted by the Transformer network, thereby emphasizing the most critical information for the identification task. Finally, more accurate defect identification is achieved based on the weighted features. The results demonstrate that this method achieves higher accuracy and stronger noise resistance compared to traditional image processing and recognition methods, making it a robust solution for cable insulation defect identification.
Unveiling mungbean yellow mosaic virus: molecular insights and infectivity validation in mung bean (Vigna radiata) via infectious clones
Authors: Balasubramaniam Madhumitha , Thangavel Tamilnayagan , Aiyanathan Karupiah Eraivan Arutkani , Rathnasamy Sakthi Ambothi , Rajagopalan Veera Ranjani , Subbarayalu Mohankumar , Natesan Senthil , Kanagarajan Selvaraju , Muthurajan Raveendran , Manickam Sudha
Published: August 2024

Yellow mosaic disease (YMD) with typical symptoms of alternating bright yellow to green patches associated with stunting, downward cupping, and wrinkling has been observed in mung bean on agricultural farms in Coimbatore, Tamil Nadu, India. PCR using gene-specific primers indicated the presence of the yellow mosaic virus in symptomatic plants. Rolling circle amplification (RCA) followed by restriction digestion detected ~2.7 kb of DNA-A and DNA-B, allowing the identification of a bipartite genome. The full-length genome sequences were deposited in NCBI GenBank with the accession numbers MK317961 (DNA-A) and MK317962 (DNA-B). Sequence analysis of DNA-A showed the highest sequence identity of 98.39% to the DNA-A of mungbean yellow mosaic virus (MYMV)-Vigna radiata (MW736047), while DNA-B exhibited the highest level of identity (98.21%) to the MYMV-Vigna aconitifolia isolate (DQ865203) reported from Tamil Nadu. Recombinant analysis revealed distinct evidence of recombinant breakpoints of DNA-A within the region encoding the open reading frame (ORF) AC2 (transcription activation protein), with the major parent identified as MYMV-PA1 (KC9111717) and the potential minor parent as MYMV-Namakkal (DQ86520.1). Interestingly, a recombination event in the common region (CR) of DNA-B, which encodes the nuclear shuttle protein and the movement protein, was detected. MYMIV-M120 (FM202447) and MYMV-Vigna (AJ132574) were identified as the event’s major and minor parents, respectively. This large variation in DNA-B led us to suspect a recombination in DNA-B. Dimeric MYMV infectious clones were constructed, and the infectivity was confirmed through agroinoculation. In future prospects, unless relying on screening using whiteflies, breeders and plant pathologists can readily use this agroinoculation procedure to identify resistant and susceptible cultivars to YMD.
The state of biosafety across China's CDC microbiology laboratories: insights from a nationwide survey (2021–2023)
Authors: Niu Peihua , Sun Zhenlu , Zhang Ruiqing , Zhao Yiming , Tian Fengyu , Cheng Ping , Zheng Hongmei , Guo Jianqiang , Zhang Meng , Ma Xuejun , Wang Ji
Published: August 2024

Background

The COVID-19 pandemic underscored the critical importance of biosafety in microbiology laboratories worldwide. In response, China has ramped up its efforts to enhance biosafety measures within its Centers for Disease Control and Prevention (CDC) laboratories. This study provides the first comprehensive assessment of biosafety practices across provincial, city, and county levels of CDC microbiology laboratories in China.

Methods

We conducted a nationwide cross-sectional survey from 2021 to 2023, targeting staff from microbiology laboratories within CDCs at all administrative levels in China. Stratified sampling was employed to select respondents, ensuring a representative mix across different CDC hierarchies, job titles, and academic qualifications. The survey encompassed questions on biosafety training, the presence of BSL-2 and BSL-3 laboratories, adherence to general biosafety guidelines, and management practices regarding specimens, reagents, and consumables. Statistical analysis was performed to identify significant differences in biosafety practices among different CDC levels.

Results

A total of 990 valid responses were received, highlighting a nearly universal presence (98.69%) of BSL-2 laboratories and a significant yet varied presence of BSL-3 laboratories across the CDC network. The survey revealed high levels of biosafety training (98.69%) and adherence to biosafety protocols. However, challenges remain in the consistent application of certain safety practices, especially at lower administrative levels. Notable differences in the management of specimens, reagents, and consumables point to areas for improvement in ensuring biosecurity.

Conclusion

Our findings indicate a robust foundation of biosafety practices within CDC microbiology laboratories in China, reflecting significant advancements in the wake of the Biosecurity Law's implementation. Nevertheless, the variability in adherence to specific protocols underscores the need for ongoing training, resources allocation, and policy refinement to enhance biosafety standards uniformly across all levels. This study's insights are crucial for guiding future improvements in laboratory biosafety, not just in China but potentially in other countries enhancing their public health infrastructures.
Recent advances in minimally invasive biomarkers of OSCC: from generalized to personalized approach
Authors: Suri Smriti , Boora Geeta S. , Kaur Rajandeep , Chauhan Anshika , Ghoshal Sushmita , Pal Arnab
Published: August 2024

Oral cancer is the 6th most common type of cancer worldwide, and oral squamous cell carcinoma (OSCC) accounts for >90% of oral cancers. It is a major health problem, particularly in low- and middle-income countries (LMICs), due to both its high incidence and significant mortality and morbidity. Despite being a global burden, and even with the significant advancement in the management of OSCC, the overall outcome of the disease is still abysmal. With the advent of time, advanced diagnostic and treatment approaches have come into practice, but the burden of the disease has not improved significantly. Major reasons attributed to the poor outcome are delay in diagnosis, locoregional recurrence and resistance to the currently available treatment regimen. In this review, we have highlighted the existing challenges in the diagnosis and have emphasized the advancements in minimally invasive biomarkers. Additionally, the importance of collaborative multidimensional approaches involving clinicians and researchers has been discussed, as well as the need to redefine and establish better utility and management of existing diagnostic and treatment protocols along with the minimally invasive/non-invasive biomarkers.
Community-centered instrumentation and monitoring of nature-based solutions for urban stormwater control
Authors: O’Brien Colleen M. , Mossman Malcolm , Chamberlain Lucas , Jenkins Jennifer , Watson John , Wilson Ryan , Williams-Clark Drew , Singer Alec , Riggio Kara , Gallet Danielle , Miller William M. , Packman Aaron I.
Published: August 2024

Climate change is increasing the frequency and severity of extreme precipitation events, requiring new ways of managing stormwater, particularly in urban areas. Nature-based solutions (NBS) have become increasingly popular to provide distributed stormwater storage while supporting urban biodiversity and access to nature. However, long-term monitoring of the hydrological performance of NBS is limited. To date most literature has focused on monitoring methodologies for specific sites and types of NBS, use of remote sensing and modeling for large-scale assessments, or measuring benefits of NBS for urban heat mitigation. More comprehensive and consistent measurement strategies are needed to understand the effects of distributed NBS on urban hydrology at the regional scale, and improve the design, maintenance, and adoption for community-centered stormwater management. To address these gaps, we review available literature on measurement methods, summarize these methods and provide specific recommendations for instrumentation and in situ monitoring of common types and scales of urban NBS. Based on our findings on performance monitoring for individual NBS sites, we extend recommendations for consistent hydrological assessment of distributed NBS at regional scale and the efficacy of NBS in reducing community flooding impacts. These recommendations are particularly applicable for municipalities, researchers and community-based organizations who are now leading the planning and implementation of community-centered NBS systems in many areas.
Neurosurgery training camp for medical student: experience of the Turkish neurosugery academy and Bursa Uludag University
Authors: Unal H. Setenay , Aydin Mevlut Okan , Bilgic Esma , Eser Pınar , Alper Zuleyha , Taskapılıoğlu M. Ozgur , İlker Kafa M. , Kocaeli Hasan , Dogan Seref , Yılmazlar Selcuk , Bekar Ahmet , Sekerci Zeki , Aksoy Kaya
Published: August 2024

Introduction

To highlight the importance of hands-on experiences and mentorship in shaping the future workforce of specialized medical professionals via a Neurosurgery Training Camp.

Methods

Responses of the questionnaire regarding the Neurosurgery Training Camp organized by Bursa Uludag University's Faculty of Medicine and the Turkish Neurosurgery Academy were reviewed retrospectively. A one-day program was organized to introduce neurosurgery to medical students. During the camp, the students participated in interactive presentations delivered by faculty members, had lunch together, became acquainted with neurosurgical tools and technologies, and performed interventions. With pre and postworkshop questionnaire, student's expectations and thoughts about camp was evaluated.

Results

Forty-one students from 10 medical schools, spanning every year of study, attended the camp. Approximately 39% of the attendees (n = 16) were women and 61% (n = 25) were men. The post-workshop survey results demonstrated that 73% of the students (n = 30) were inclined to pursue a career in neurosurgery after the camp, 21.9% (n = 9) remained undecided, and 4.8% (n = 2) chose not to pursue neurosurgery. Feedback from the post-workshop questionnaire highlighted that all students perceived the camp as beneficial in providing insights into their future careers and aiding in making a decision regarding their career paths.

Discussion

The neurosurgical training camp effectively inspired and educated medical students about the discipline of neurosurgery. Furthermore, the camp effectively altered the career aspirations and perceptions of neurosurgery among the participating students.