bluuebunny/crossref_metadata_2025 huggingface dataset:
Trustworthiness in the Media Industry and its Significance for the Strategic Programme Planning of Moving Image Providers in Germany
Authors: Jenne M.A. Timo , Joachim Prof. Dr. Eigler,
Published: October 2024

This paper examines the evolving landscape of strategic program planning in Germany's media industry, focusing on the integral role of trustworthiness for linear TV broadcasters and streaming service providers. In media convergence and dynamic market structures, we analyze how trustworthiness is cultivated and leveraged as a strategic asset in program planning decisions. Conduct a comprehensive literature review, we delve into the resource-based view to understand trustworthiness as a rare and inimitable resource, crucial for sustaining competitive advantage in the rapidly changing media sector. The study compares and contrasts the strategic approaches of linear broadcasters and streaming service providers, highlighting their distinct and converging tactics in response to shifting audience preferences and technological advancements. We also explore the impact of brand identity on trust establishment, and how programming strategies are influenced by the audience's evolving consumption patterns. The findings illuminate the nuanced interplay between program planning and trustworthiness, offering insights into future trends and underscoring the need for adaptable, audience-centric strategies to pursue sustainable market success in the media industry.
Study of Two-phase Flow and Heat Transfer Characteristics of Double Fulcrum Counter-rotating Bearing Chamber
Authors:   Northwestern Polytechnical University, Zhu Zetao , Lyu Yaguo ,   Northwestern Polytechnical University, Cao Yitao ,   Northwestern Polytechnical University, Liu Zhenxia ,   Northwestern Polytechnical University
Published: October 2024

The counter-rotation of dual rotors presents significant advantages in mitigating the gyroscopic effects inherent in aircraft engines. In this paper, a numerical investigation was conducted to analyze the flow and heat transfer characteristics within the double fulcrum bearing chamber using the CLSVOF method. Upon comparing the flow field characteristics within the bearing chamber under differing rotational directions of the high and low-pressure shafts, further investigation explored the impact of rotational speeds and bilateral oil flow rates on the flow and heat transfer characteristics of the bearing chamber. The results indicate that under counter-rotation, significant flow vortices are generated within the double fulcrum bearing chamber, causing opposing directions of wall streamlines, and thereby rendering the complexity of the flow dynamics. With increasing counter-rotating speed or speed ratio, the volume fraction of oil on the wall increases while the oil film thickness decreases. The oil film speed significantly increases. When the bilateral oil supply or oil flow rate ratio is higher, both the volume fraction of oil on the wall and the oil film thickness increase, but the increase in oil film speed is relatively small. Increasing the rotation speed and oil flow rate can enhance the wall heat transfer coefficient.
An experimental study of the deposition on plates with different film-cooling hole shapes
Authors:   School of Power and Energy, Northwesten Polytechnical University, Liu Zhengang , Zhang Yixuan ,   School of Power and Energy, Northwesten Polytechnical University, Liu Zhenxia ,   School of Power and Energy, Northwesten Polytechnical University
Published: October 2024

The deposition of particles, such as sands, dusts and volcanic ashes, on turbines could reduce the aerodynamic and cooling performance of turbines. To investigate the effect of film-cooling with different hole shapes on the deposition, an experiment at about ambient temperature is designed, in which the test models are plates but with different film-cooling hole shapes and a kind of wax is atomized as the particles. The results show that for the blowing-ratio 3.0, the conical filmcooling hole could reduce the deposition rate 83% than the cylindrical film-cooling hole, and the covering-slot (CONSOLE) film-cooling hole could reduce the deposition rate 69%, although most deposition forms near the film-cooling holes for all film-cooling holes shapes. The film-cooling efficiency of the plate with the conical hole could be improved by up to 13% than cylindrical film-cooling hole, and the CONSOLE film-cooling hole could be improved by up to 21%. For the cylindrical film-cooling, at 2D ~ 15D after the film-cooling holes, the average cooling efficiency in the spanwise direction is improved after the experiment, and the maximum is increased by about 1.8% at X / D=6. From 15D to the tail, the average efficiency in the spanwise direction decreases by about 1.3% after the experiment. The average cooling efficiency of the conical hole is reduced by about 0.12% after the experiment, and the CONSOLE film hole structure has no obvious change. This study may be helpful for developing the technology of reducing the deposition and its harm on turbines.
The Effect of Chemical Kinetic Mechanisms on the Flame Transfer Function
Authors:   Trinity College Dublin, Thomas Cillian , Spence Stephen ,   Trinity College Dublin, Stuart Charles ,   Trinity College Dublin, Jella Sandeep ,   Siemens Energy Canada Ltd, Füri Marc ,   Siemens Energy Canada Ltd, Bourque Gilles ,   McGill University
Published: October 2024

This paper reports the investigation of the effect of chemical kinetic mechanisms on the thermoacoustic behaviour of a premixed combustor test rig. This was done by exploring the flame transfer function (FTF) of three chemical kinetic mechanisms; a global (6 species, 2 reaction) mechanism, a reduced (19 species, 55 reaction) mechanism and a detailed (53 species, 325 reaction) mechanism. Chemistry was computed using a tabulated chemistry approach, and FTF’s were computed using a large eddy simulation (LES) along with a system identification method (SI). The LES results of each of the 3 chemical mechanisms were quite similar for mean results, but the dynamic (and hence thermoacoustic) results depended significantly on the chosen chemical mechanism. Despite this, the global and detailed mechanisms showed similar FTF results, which indicated that significant computational savings may be achieved in the pre-processing step of pre-tabulation provided that the global mechanism can compute the unit impulse response (UIR) with sufficient accuracy. These computational savings will allow rapid assessment and optimization of future clean energy systems.
Experimental Characterisation of a Novel Double Scroll Wastegate Connection Valve Design for Turbochargers
Authors:   Imperial College London, Ale Pablo , Freytag Oskar ,   Imperial College London, Noon Chris ,   Imperial College London, Martinez-Botas Ricardo F ,   Imperial College London, Yasuaki Jinnai ,   Mitsubishi Heavy Industries
Published: October 2024

The automotive sector is going through a major transition. Despite the rapid onset of electric mobility, developing simple and effective solutions to improve turbocharger performance remains an important task. The present work aims to do so by developing a novel wastegate design methodology which allows scroll connection to take place for doubleentry turbines. The design presented seeks to isolate both turbine inlets when the engine operates at low RPM, achieving high torque, while increasing the flow between the two inlets when the engine operates at high RPM, reducing the back pressure and, thus, the pumping losses. The novel turbine involves cutting back the wall that divides the two wastegate channels, allowing the cross-flow to be regulated. The research aims to capture the performance of the proposed new concept experimentally. To characterise the cross-flow behaviour, a novel test rig was developed using an innovative “scroll-bypass” method to isolate the wastegate from the rotor. The approach has been verified as feasible through preliminary CFD and allows for calculating cross-flows and wastegate mass flows at different operating conditions. The paper describes the new wastegate characterisation strategy and presents the results for 3 different configurations of the cutting-back wall.
The Effect of Self-Efficacy and Family Support toward Self-Confidence of Accounting and Financial Institution Students
Authors: Nur'aini Anisa , Wibawa Eka Ary , Fahrul Rijal
Published: October 2024

Self-confidence is one of the essential skills that students still lack. This research aims to know the effect of: 1) Self-Efficacy on Self-Confidence, 2) Family Support on Self-Confidence, and 3) Self-Efficacy and Family Support simultaneously on the self-confidence of grade XI and XII students of Accounting and Financial Institution of SMK N 1 Pengasih Academic Year 2023/2024. This research is ex post facto research with a quantitative approach. This research was conducted at SMK N 1 Pengasih with a sample of 105 students in class XI and XII Accounting and Financial Institution. The results of this research showed that: 1) There is a positive and significant effect of self-efficacy on students' self-confidence by 32,1%. 2) There is a positive and significant effect of family support on students' self-confidence by 6,5%. 3) There is a positive and significant effect of self-efficacy and family support simultaneously on students' self-confidence by 36.%.
The Relationship of Academic Burnout and Internet Addiction in Academic Achievement: The Mediating Role of Optimism in Students
Authors: Novian Candra Kurniawan Candra , Khusnul Khotimah  , Zerina Nurkhamamah
Published: October 2024

For students, academic achievement is significant. In addition to providing motivation, academic achievement also makes it easier for students to continue to the next level of education. However, academic burnout and internet addiction sometimes prevent them from achieving academic achievement. Therefore, this study examined the relationship between academic burnout and internet addiction. This study also includes optimism as an intervention variable. The research method used in this study is quantitative with explanatory type. The population in this study were ninth-grade students at SMP Negeri 11 Malang, with a sample of 72 students using the Slovin formula. Data were collected using a questionnaire, which was then distributed to respondents. One hundred fifteen respondents were obtained, and the results were then analyzed using partial least squares with the help of the SMART-PLS application. Direct and indirect results, such as overall academic burnout, hurt academic achievement and optimism. However, positive results were shown for internet addiction on academic achievement and optimism. This finding implies that excessive tasks and responsibilities lead to burnout and decreased academic performance. However, internet addiction in students can have a positive impact if used as a relevant learning resource.
Allah Mencari Manusia Berdosa: Sebuah Analisa Sastra Teks Kejadian 3:8-19
Authors: Kristiawan Ragil
Published: October 2024

Genesis chapter 3 narrates the entry of sin into the world and its consequence, original sin, for all of humanity. Amid this darkness, there is a glimmer of hope in the narrative, as God actively seeks out sinful humanity. This study aims to examine God's response to humankind after the fall into sin. Utilizing a qualitative literature study method, this research conducts a literary analysis of Genesis 3:8-19. The analysis includes translating the BHS text, constructing the text’s structure, character analysis, literary structure, and examining the dramatic flow of the text. The literary analysis yields three key findings. First, it is God who takes the initiative to seek out humanity after the fall into sin. God’s role as the protagonist in this narrative serves as key evidence of His desire to communicate with and save fallen humanity. The context of the fall and God's initiative to approach humanity underscores His pivotal role as the protagonist in this story. Second, while God seeks out sinners, His discipline still applies to those who violate His commands. This is clearly reflected in the dramatic structure intentionally crafted by the biblical author. Third, God takes the initiative to provide a solution to the problem of sin. The enmity established by God between the serpent and the offspring of the woman indicates His effort to deliver humanity from the bondage of sin.
Prinsip Dasar Kualitas Seorang Pengajar Kristen di Gereja Menurut 1 Timotius 4:6-8
Authors: Baskoro Paulus Kunto , Matulessy Yosua Yosia
Published: October 2024

Since the beginning, Christian education has come from the church, the church has become the center or center of Christian religious education so that Christian education in the church should be taken seriously, quality and quality should be improved. The church in the modern era needs qualified teaching staff. The quality of a teacher can be reviewed in the letter 1 Timothy 4:6-8 which is the topic of discussion in this article. By using a qualitative method and an interpretive approach (interpretative design) the author observes the text of 1 Timothy 4:6-8 with the principle of hermeneutic interpretation to reveal and explain the basic principles regarding the quality of Christian teachers in the church. The results found are that the quality of Christian teachers must have knowledge of the scriptures (intellectual) as a basis for teaching and have a good spiritual life (spiritual).
Dielectrophoretic capture of Escherichia coli and boar sperms using ULSI-fabricated three-dimensional protruding TiN nano-electrode arrays
Authors: Lu Hua-Jung , Liao I-Hsuan , Lien Chun-Lung , Shiau Jeng-Huei , Shen Ching-Fen , Chou Kuan-Ru , Cheng Chao-Min
Published: October 2024

Object

In recent years, dielectrophoresis has become widely recognized as a highly suitable method for creating good tools for particle separation, with significant successes achieved in a variety of areas.

Method

Expanding upon this, we adopted a semiconductor CMOS process, instead of a MEMS process, which allowed for the following: 1) wire insulation to mitigate Joule heat and prevent thermal fluctuation interference with the dielectrophoretic force; 2) isolation of harmful materials from biological samples, making the chip biocompatible; and, 3) the ability to employ nano-electrodes capable of generating a stronger electric field than conventional electrodes, thus allowing chip capture at lower voltages. Additionally, our chip is scalable, enabling multiplied throughput based on sample processing requirements.

Results and Dissusion

These features make our chip more widely applicable and suitable for capturing bacteria and sperm. In this study, we focused on optimizing the parameters of dielectrophoresis and employed 3-D protruding TiN nano-electrode arrays to facilitate the capture of Escherichia coli and boar sperms. The experimental data demonstrates that the capture efficiency of this chip for E. coli was approximately 79.25% ± 2.66%, and the highest capture efficiency for sperms was approximately 39.2% ± 3.9%.
Unraveling the intricate link between cell death and neuroinflammation using Drosophila as a model
Authors: Rai Pooja , Bergmann Andreas
Published: October 2024

Protein aggregation is a common pathological occurrence in neurodegenerative diseases. This often leads to neuroinflammation, which exacerbates the aggregation and progression of diseases like Parkinson’s and Alzheimer’s. Here, we focus on immune responses and neurotoxicity in a Parkinson’s disease model in Drosophila. Mutations in the SNCA gene that encodes the alpha (α)-Synuclein protein have been linked to familial Parkinson’s disease, disrupting autophagy regulation in neuronal cells and promoting the formation of Lewy bodies, a hallmark of Parkinson’s pathology. This results in the loss of dopaminergic neurons, manifesting as movement disorders. α-Synuclein aggregation triggers innate immune responses by activating microglial cells, leading to phagocytic activity and the expression of neuroprotective antimicrobial peptides (AMPs). However, sustained AMP expression or chronic inflammation resulting from inadequate microglial phagocytosis can induce neuronal toxicity and apoptosis, leading to severe dopaminergic neuron loss. This review underscores the mechanistic connection between immune response pathways and α-Synuclein-mediated neurodegeneration using Drosophila models. Furthermore, we extensively explore factors influencing neuroinflammation and key immune signaling pathways implicated in neurodegenerative diseases, particularly Parkinson’s disease. Given the limited success of traditional treatments, recent research has focused on therapies targeting inflammatory signaling pathways. Some of these approaches have shown promising results in animal models and clinical trials. We provide an overview of current therapeutic strategies showing potential in treating neurodegenerative diseases, offering new avenues for future research and treatment development.
Recombinant adenoviruses expressing HPV16/18 E7 upregulate the HDAC6 and DNMT3B genes in C33A cells
Authors: Shao Yunting , Shah Pir Tariq , Su Qisheng , Li Shanhu , Huang Fang , Wang Jun , Wang Peng , Wu Chengjun
Published: October 2024

Objective

High-risk human papillomavirus (HPV) is a carcinogenic virus associated with nearly all cases of cervical cancer, as well as an increasing number of anal and oral cancers. The two carcinogenic proteins of HPV, E6 and E7, can immortalize keratinocytes and are essential for HPV-related cellular transformation. Currently, the global regulatory effects of these oncogenic proteins on the host proteome are not fully understood, and further exploration of the functions and carcinogenic mechanisms of E6 and E7 proteins is needed.

Methods

We used a previously established platform in our laboratory for constructing recombinant adenoviral plasmids expressing the HPV16 E7 gene to further construct recombinant virus particles expressing HPV16/18 E6, E7, and both E6 and E7 genes. These recombinant viruses were used to infect C33A cells to achieve sustained expression of the HPV16/18 E6/E7 genes. Subsequently, total RNA was extracted and RNA-Seq technology was employed for transcriptome sequencing to identify differentially expressed genes associated with HPV infection in cervical cancer.

Results

RNA-Seq analysis revealed that overexpression of the HPV16/18 E6/E7 genes upregulated GP6, CD36, HDAC6, ESPL1, and DNMT3B among the differentially expressed genes (DEGs) associated with cervical cancer. Spearman correlation analysis revealed a statistically significant correlation between the HDAC6 and DNMT3B genes and key pathways, including DNA replication, tumor proliferation signature, G2M checkpoint, p53 pathways, and PI3K/AKT/mTOR signaling pathways. Further, qRT-PCR and Western blot analyses indicated that both HPV16/18 E7 can upregulate the expression of HDAC6 and DNMT3B, genes associated with HPV infection-related cervical cancer.

Conclusion

The successful expression of HPV16/18 E6/E7 in cells indicates that the recombinant viruses retain the replication and infection capabilities of Ad4. Furthermore, the recombinant viruses expressing HPV16/18 E7 can upregulate the HDAC6 and DNMT3B genes involved in cervical cancer pathways, thereby influencing the cell cycle. Additionally, HDAC6 and DNMT3B are emerging as important therapeutic targets for cancer. This study lays the foundation for further exploration of the oncogenic mechanisms of HPV E6/E7 and may provide new directions for the treatment of HPV-related cancers.
Causal association between common rheumatic diseases and arrhythmia: a Mendelian randomization study
Authors: Zhang Yuchen , Tang Ling , Zhang Ke , Meng Xinai , Liu Tian , Chen Yanjia , Huang Xingfu
Published: October 2024

Background

Observational studies have suggested a link between rheumatic diseases and arrhythmias. However, these studies have been limited by confounding factors and reverse causality, leaving the causal relationship between rheumatic diseases and arrhythmias uncertain. This study addresses this inquiry using genetic evidence.

Methods

Selected single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) data were employed as instrumental variables. Inverse variance weighting (IVW), MR-Egger regression, and the weighted median method were utilized in the two-sample Mendelian randomization analysis. Horizontal pleiotropy was identified and rectified through the MR-PRESSO test and MR-Egger regression. The stability and reliability of the Mendelian randomization results were appraised using the remain-one method, Cochran Q-test, and funnel plot. Odds ratios (OR) were utilized to assess the causal relationship between six rheumatic diseases and five types of arrhythmias.

Results

The Inverse Variance Weighted (IVW) method indicated a significant association between rheumatoid arthritis (RA) and an elevated risk of right bundle branch block (RBBB) (OR: 1.10, 95% CI: 1.02–1.18, p = 0.009). Additionally, gout was significantly correlated with an augmented risk of RBBB (OR: 1.28, 95% CI: 1.09–1.51, p = 0.003). Conversely, dermatomyositis (DM) exhibited a negative association with the risk of atrioventricular block (AVB) (OR: 0.94, 95% CI: 0.90–0.99, p = 0.020). No significant associations were observed between other rheumatic diseases and arrhythmias.

Conclusion

A two-sample Mendelian Randomization (MR) study provides data indicating that in European populations, a genetically predicted gout or rheumatoid arthritis (RA) may increase the incidence of right bundle branch block (RBBB). To clarify and investigate the processes behind these causal links, more research is necessary. Because racial genetic variability exists, care should be used when interpreting our findings.
Differential expression of cardiometabolic and inflammation markers and signaling pathways between overweight/obese Qatari adults with high and low plasma salivary α-amylase activity
Authors: Khalifa Olfa , Al-Akl Neyla S. , Arredouani Abdelilah
Published: October 2024

Background

The relationship between salivary α-amylase activity (sAAa) and susceptibility to cardiovascular disorders lacks a definitive consensus in available studies. To fill this knowledge gap, the present study endeavors to investigate this association among overweight/obese otherwise healthy Qatari adults. The study specifically categorizes participants based on their sAAa into high and low subgroups, aiming to provide a more comprehensive understanding of the potential link between sAAa levels and cardiovascular and inflammation markers in this population.

Methods

Plasma samples of 264 Qatari overweight/obese (Ow/Ob) participants were used to quantify the sAAa and to profile the proteins germane to cardiovascular, cardiometabolic, metabolism, and organ damage in low sAAa (LsAAa) and high sAAa (HsAAa) subjects using the Olink technology. Comprehensive statistical tools as well as chemometric and enrichments analyses were used to identify differentially expressed proteins (DEPs) and their associated signaling pathways and cellular functions.

Results

A total of ten DEPs were detected, among them five were upregulated (QPCT, LCN2, PON2, DPP7, CRKL) while five were down regulated in the LsAAa subgroup compared to the HsAAa subgroup (ARG1, CTSH, SERPINB6, OSMR, ALDH3A). Functional enrichment analysis highlighted several relevant signaling pathways and cellular functions enriched in the DEPs, including myocardial dysfunction, disorder of blood pressure, myocardial infraction, apoptosis of cardiomyocytes, hypertension, chronic inflammatory disorder, immunes-mediated inflammatory disease, inflammatory response, activation of leukocytes and activation of phagocytes.

Conclusion

Our study unveils substantial alterations within numerous canonical pathways and cellular or molecular functions that bear relevance to cardiometabolic disorders among Ow/Ob Qatari adults exhibiting LsAAa and HsAAa in the plasma. A more comprehensive exploration of these proteins and their associated pathways and functions offers the prospect of elucidating the mechanistic underpinnings inherent in the documented relationship between sAAa and metabolic disorders.
Parallel and scalable AI in HPC systems for CFD applications and beyond
Authors: Sarma Rakesh , Inanc Eray , Aach Marcel , Lintermann Andreas
Published: October 2024

This manuscript presents the library AI4HPC with its architecture and components. The library enables large-scale trainings of AI models on High-Performance Computing systems. It addresses challenges in handling non-uniform datasets through data manipulation routines, model complexity through specialized ML architectures, scalability through extensive code optimizations that augment performance, HyperParameter Optimization (HPO), and performance monitoring. The scalability of the library is demonstrated by strong scaling experiments on up to 3,664 Graphical Processing Units (GPUs) resulting in a scaling efficiency of 96%, using the performance on 1 node as baseline. Furthermore, code optimizations and communication/computation bottlenecks are discussed for training a neural network on an actuated Turbulent Boundary Layer (TBL) simulation dataset (8.3 TB) on the HPC system JURECA at the Jülich Supercomputing Centre. The distributed training approach significantly influences the accuracy, which can be drastically compromised by varying mini-batch sizes. Therefore, AI4HPC implements learning rate scaling and adaptive summation algorithms, which are tested and evaluated in this work. For the TBL use case, results scaled up to 64 workers are shown. A further increase in the number of workers causes an additional overhead due to too small dataset samples per worker. Finally, the library is applied for the reconstruction of TBL flows with a convolutional autoencoder-based architecture and a diffusion model. In case of the autoencoder, a modal decomposition shows that the network provides accurate reconstructions of the underlying field and achieves a mean drag prediction error of ≈5%. With the diffusion model, a reconstruction error of ≈4% is achieved when super-resolution is applied to 5-fold coarsened velocity fields. The AI4HPC library is agnostic to the underlying network and can be adapted across various scientific and technical disciplines.
Prognostic significance of fludeoxyglucose positron emission tomography delta radiomics following bridging therapy in patients with large B-cell lymphoma undergoing CAR T-cell therapy
Authors: Ladbury Colton , Hao Claire , Watkins William Tyler , Sampath Sagus , Wong Jeffrey , Amini Arya , Sokolov Karen , Yeh Jekwon , Al Feghali Karine A. , de Jong Dorine , Maniyedath Arjun , Shirvani Shervin , Nikolaenko Liana , Mei Matthew , Herrera Alex , Popplewell Leslie , Budde Lihua Elizabeth , Dandapani Savita
Published: October 2024

Purpose/objective(s)

Bridging radiation therapy (bRT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). It is unknown how the extent of cytoreduction during bRT impacts outcomes.

Materials/methods

We retrospectively reviewed patients with LBCL treated with bRT followed by CAR T-cell therapy. Metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), SUVmean, and total lesion glycolysis (TLG) were extracted from F18-fluorodeoxyglucose positron emission tomography (PET) scans acquired prior to bRT and between completion of bRT and CAR T-cell infusion. Delta radiomics based on changes of these values were then calculated. The association between delta radiomics and oncologic outcomes [progression-free survival (PFS), freedom from distant progression (FFDP), and local control (LC)] were then examined.

Results

Thirty-three sites across 23 patients with LBCL were irradiated. All metabolically active disease was treated in 10 patients. Following bRT, median overall decreases (including unirradiated sites) in MTV, SUVmax, SUVmean, and TLG were 22.2 cc (63.1%), 8.9 (36.8%), 3.4 (31.1%), and 297.9 cc (75.8%), respectively. Median decreases in MTV, SUVmax, SUVmean, and TLG in irradiated sites were 15.6 cc (91.1%), 17.0 (74.6%), 6.8 (55.3%), and 157.0 cc (94.6%), respectively. Median follow-up was 15.2 months. A decrease in SUVmax of at least 54% was associated with improved PFS (24-month PFS: 83.3% vs. 28.1%; p = 0.037) and FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). A decrease in MTV of at least 90% was associated with improved FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). LC was improved in sites with decreases in SUVmax of at least 71% (24-month LC: 100% vs. 72.7%; p < 0.001). Decreases of MTV by at least 90% (100% vs. 53.3%; p = 0.038) and TLG by at least 95% (100% vs. 56.3%; p = 0.067) were associated with an improved complete response rate.

Conclusion

bRT led to substantial reductions in MTV, SUVmax, SUVmean, and TLG. The relative extent of these decreases correlated with improved outcomes after CAR T-cell infusion. Prospective cohorts should validate the value of interim PET following bRT for quantifying changes in disease burden and associated prognosis.
Cluster of differentiation-44 as a novel biomarker of lupus nephritis and its role in kidney inflammation and fibrosis
Authors: Wong Caleb C.Y. , Gao Lucy Y. , Xu Yuesong , Chau Mel K.M. , Zhang Danting , Yap Desmond Y.H. , Ying Shirley K.Y. , Lee Cheuk Kwong , Yung Susan , Chan Tak Mao
Published: October 2024

Introduction

CD44 is a transmembrane glycoprotein implicated in tissue inflammation and fibrosis. We investigated its role in kidney inflammation and fibrosis in a murine model of lupus nephritis (LN), and the clinico-pathological association of serum CD44 level in patients with biopsy-proven Class III/IV ± V LN.

Methods

NZB/W F1 mice were treated with control IgG or anti-CD44 monoclonal antibody for 4 weeks and disease parameters assessed. Serum CD44 level in LN patients was determined by ELISA. Control groups included healthy subjects and patients with non-renal SLE or non-lupus renal disease.

Results

CD44 expression was absent in the normal kidney, but it was expressed in proximal and distal tubular epithelial cells and infiltrating cells in renal biopsies from patients with active proliferative LN. ScRNA-Seq datasets confirmed that CD44 was predominantly expressed in tubular cells and all immune cells identified in LN patients including tissue resident, inflammatory and phagocytic macrophages, Treg cells, effector and central memory CD4+ T cells, resident memory CD8+ T cells and naïve and activated B cells. Treatment of NZB/W F1 mice with anti-CD44 antibody preserved kidney histology and reduced proteinuria, tubulo-interstitial infiltration of CD3+, CD4+ and CD19+ immune cells, and mediators of kidney fibrosis compared to Control mice. Longitudinal studies showed that serum CD44 level increased prior to clinical renal flare by 4.5 months and the level decreased after treatment. ROC curve analysis showed that CD44 level distinguished patients with active LN from healthy subjects and patients with quiescent LN, active non-renal lupus, and non-lupus CKD (ROC AUC of 0.99, 0.96, 0.99 and 0.99 respectively). CD44 level correlated with leukocyte infiltration and interstitial inflammation scores in active LN kidney biopsies.

Discussion

Our findings suggest that CD44 plays a pathogenic role in renal parenchymal inflammation and fibrosis in active LN and monitoring CD44 may facilitate early diagnosis of flare.
TNF-α inhibitors for type 1 diabetes: exploring the path to a pivotal clinical trial
Authors: Bazile Cassandra , Abdel Malik Magdy M. , Ackeifi Courtney , Anderson Randy L. , Beck Roy W. , Donath Marc Y. , Dutta Sanjoy , Hedrick Joseph A. , Karpen Stephen R. , Kay Thomas W. H. , Marder Thomas , Marinac Marjana , McVean Jennifer , Meyer Robert , Pettus Jeremy , Quattrin Teresa , Verstegen Ruud H. J. , Vieth Joshua A. , Latres Esther
Published: October 2024

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. This destruction leads to chronic hyperglycemia, necessitating lifelong insulin therapy to manage blood glucose levels. Typically diagnosed in children and young adults, T1D can, however, occur at any age. Ongoing research aims to uncover the precise mechanisms underlying T1D and to develop potential interventions. These include efforts to modulate the immune system, regenerate β-cells, and create advanced insulin delivery systems. Emerging therapies, such as closed-loop insulin pumps, stem cell-derived β-cell replacement and disease-modifying therapies (DMTs), offer hope for improving the quality of life for individuals with T1D and potentially moving towards a cure. Currently, there are no disease-modifying therapies approved for stage 3 T1D. Preserving β-cell function in stage 3 T1D is associated with better clinical outcomes, including lower HbA1c and decreased risk of hypoglycemia, neuropathy, and retinopathy. Tumor Necrosis Factor alpha (TNF-α) inhibitors have demonstrated efficacy at preserving β-cell function by measurement of C-peptide in two clinical trials in people with stage 3 T1D. However, TNF-α inhibitors have yet to be evaluated in a pivotal trial for T1D. To address the promising clinical findings of TNF-α inhibitors in T1D, Breakthrough T1D convened a panel of key opinion leaders (KOLs) in the field. The workshop aimed to outline an optimal clinical path for moving TNF-α inhibitors to a pivotal clinical trial in T1D. Here, we summarize the evidence for the beneficial use of TNF-α inhibitors in T1D and considerations for strategies collectively identified to advance TNF-α inhibitors beyond phase 2 clinical studies for stage 3 T1D.
Emergence and evolution of mosaic penA-60 and penA-237 alleles in a Neisseria gonorrhoeae core genogroup that was historically susceptible to extended spectrum cephalosporins
Authors: Thomas IV Jesse C. , Cartee John C. , Hebrank Katherine , St. Cyr Sancta B. , Schlanger Karen , Raphael Brian H. , Kersh Ellen N. , Joseph Sandeep J.
Published: October 2024

Introduction

Neisseria gonorrhoeae (Ng) has successively developed resistance to all previously recommended antimicrobial therapies, with ceftriaxone being the last option for monotherapy of gonorrhea. Global emergence and international spread of the FC428 clone derived mosaic penA-60 allele, associated with highlevel ceftriaxone minimum inhibitory concentrations (MICs) in non FC428 clone Ng lineages, has become an increasing concern. The penA-60 allele carrying Ng was first identified in the U.S. in Las Vegas, Nevada (2019; GCWGS-102723), with a multi-locus sequence type (MLST)-1901 strain, in a non FC428 clone Ng lineage, which is associated with a historically ceftriaxone susceptible core genogroup. Later in 2022, an allele genetically similar to penA-60, mosaic penA-237, was identified in the UK (H22-722) and France (F92) with high-level ceftriaxone MICs and both belonged to MLST-1901.

Methods

In this study, we assessed phylogenomic relatedness and antimicrobial resistance (AMR) determinant profiles of these three isolates with high-level ceftriaxone MICs among a global collection of 2,104 genomes belonging to the MLST-1901 core genome cluster group 31, which includes strains separated by a locus threshold of 200 or fewer differences (Ng_cgc_200). Recombination events in and around the penA coding region were catalogued and potential sources of inter species recombinant DNA were also inferred.

Results

The global population structure of MLST-1901 core genogroup falls into 4 major lineages. Isolates GCWGS-10723, F92, and H22-722 clustered within Lineage 1, which was dominated by non-mosaic penA-5 alleles. These three isolates formed a clade within Lineage 1 that consisted of isolates from North America and southeast Asia. Neisseria subflava and Neisseria sicca were identified as likely progenitors of two independent recombination events that may have led to the generation of mosaic penA-60 and penA-237, within a possible non-mosaic penA-5 background.

Discussions

Our study suggests that there are multiple evolutionary pathways that could generate concerning mosaic penA alleles via homologous recombination of historically susceptible Ng lineages with Neisseria commensals. Enhanced surveillance of gonococcal strains and Neisseria commensals is crucial for understanding of the evolution of AMR, particularly in less-studied regions (e.g., Asia), where high-level ceftriaxone MICs and multi-drug resistance are more prevalent.
Variations in the structure and function of the soil fungal communities in the traditional cropping systems from Madeira Island
Authors: Oliveira Maria Cristina O. , Alves Artur , Fidalgo Cátia , de Freitas José G. R. , Pinheiro de Carvalho Miguel A. A.
Published: October 2024

Agricultural soils are responsible for ecological functions and services that include primary production of food, fiber and fuel, nutrient cycling, carbon cycling and storage, water infiltration and purification, among others. Fungi are important drivers of most of those ecosystem services. Given the importance of fungi in agricultural soils, in this study, we aimed to characterize and analyse the changes of the soil fungal communities of three cropping systems from Madeira Island, where family farming is predominant, and investigate the response of fungi and its functional groups to soil physicochemical properties. To achieve that, we sequenced amplicons targeting the internal transcribed spacer 1 (ITS1) of the rRNA region, to analyse soil samples from 18 agrosystems: 6 vineyards (V), 6 banana plantations (B) and 6 vegetable plantations (H). Our results showed that alpha diversity indices of fungal communities are similar in the three cropping systems, but fungal composition and functional aspects varied among them, with more pronounced differences in B. Ascomycota, Basidiomycota, and Mortierellomycota were the main phyla found in the three cropping systems. Agaricomycetes and Sordariomycetes are the predominant classes in B, representing 23.8 and 22.4%, respectively, while Sordariomycetes (27.9%) followed by Eurotiomycetes (12.3%) were the predominant classes in V and Sordariomycetes (39.2%) followed by Tremellomycetes (8.9%) in the H. Saprotrophs are the fungal group showing higher relative abundance in the three cropping systems, followed by plant pathogens. Regarding symbionts, endophytes were highly observed in B, while mycorrhizal fungi was predominant in V and H. The structure of fungal communities was mainly correlated with soil content of P, K, N, Fe, and Cu. In addition, we identified bioindicators for each cropping system, which means that cultivated crops are also drivers of functional groups and the composition of communities. Overall, the three cropping systems favored diversity and growth of taxa that play important roles in soil, which highlights the importance of conservative management practices to maintain a healthy and resilient agrosystem.
Synergistic co-evolution of rhizosphere bacteria in response to acidification amelioration strategies: impacts on the alleviation of tobacco wilt and underlying mechanisms
Authors: Bian-hong Zhang , Li-na Tang , Ri-kun Li , Rui-xin Pan , Lin-dong You , Xiao-yan Chen , Kai-wen Yang , Wen-xiong Lin , Jin-wen Huang
Published: October 2024

Soil acidification represents a severe threat to tobacco cultivation regions in South China, exacerbating bacterial wilt caused by Ralstonia solanacearum. The comprehension of the underlying mechanisms that facilitate the restoration of rhizosphere microbial communities in “healthy soils” is imperative for ecologically managing tobacco bacterial wilt. This study focuses on acidified tobacco soils that have been subjected to continuous cultivation for 20 years. The experimental treatments included lime (L), biochar (B), and a combination of lime and biochar (L+B), in addition to a control group (CK). Utilizing rhizosphere biology and niche theory, we assessed disease suppression effects, changes in soil properties, and the co-evolution of the rhizosphere bacterial community. Each treatment significantly reduced tobacco bacterial wilt by 16.67% to 20.14% compared to the control group (CK) (p < 0.05) and increased yield by 7.86% to 27.46% (p < 0.05). The biochar treatment (B) proved to be the most effective, followed by the lime-biochar combination (L+B). The key factors controlling wilt were identified through random forest regression analysis as an increase in soil pH and exchangeable bases, along with a decrease in exchangeable acidity. However, lime treatment alone led to an increase in soil bulk density and a decrease in available nutrients, whereas both biochar and lime-biochar treatments significantly improved these parameters (p < 0.05). No significant correlation was found between the abundance of Ralstonia and wilt incidence. Nonetheless, all treatments significantly expanded the ecological niche breadth and average variation degree (AVD), enhanced positive interactions and cohesion within the community, and intensified negative interactions involving Ralstonia. This study suggests that optimizing community niches and enhancing pathogen antagonism are key mechanisms for mitigating tobacco wilt in acidified soils. It recommends using lime-biochar mixtures as soil amendments due to their potential ecological and economic benefits. This study offers valuable insights for disease control strategies and presents a novel perspective for research on Solanaceous crops.
Sequence analysis of the GP5 protein of porcine reproductive and respiratory syndrome virus in Vietnam from 2007 to 2023
Authors: Li Gan , Li Yilong , He Cuihua , Liu Xiyu , Lv Chen , Liu Kexin , Yu Xingang , Zhao Mengmeng
Published: October 2024

Introduction

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent 13 of porcine reproductive and respiratory syndrome (PRRS), which is one of the most economically 14 devastating viruses in the Vietnamese swine industry.

Methods

With a view toward determining the 15 genetic variation among PRRSV strains in Vietnam, we examined 271 PRRSV GP5 protein 16 sequences obtained from strains isolated in Vietnam from 2007 to 2023, for which we constructed 17 phylogenetic trees. Additionally, a collection of 52 PRRSV-1 strains and 80 PRRSV-2 strains 18 isolated in different years were specifically selected for nucleotide and amino acid homology analysis 19 and amino acid sequence alignment.

Results

The results revealed 76.1%–100.0% nucleotide and 20 75.2%–100.0% amino acid homologies for the PRRSV-1 GP5 gene, and 81.8%–100.0% nucleotide 21 and 81.1%–100.0% amino acid homologies for the PRRSV-2 GP5 gene. Amino acid mutation sites 22 in PRRSV-2 were found to be primarily distributed in the signal peptide region, antigenic sites, two 23 T-cell antigen regions, two highly variable regions (HVRs), and in the vicinity of the neutralizing 24 epitope, with a deletion mutation occurring in the neutralizing epitope, whereas amino acid mutations 25 in the PRRSV-1 sequences were found to occur predominantly in two T-cell epitopes. Genetic 26 analysis revealed that PRRSV-1 strains in Vietnam are of subtype 1 (Global), whereas PRRSV-2 27 strains are categorized into sublineages L1A, L5A, and L8E, with L8E being the predominantly 28 prevalent strain at present. Recombination analyses indicated that no significant recombination 29 events have occurred in any of the assessed 271 Vietnamese PRRSV strains.

Discussion

Our 30 analyses of 271 Vietnamese PRRSV strains have yielded valuable insights regarding the 31 epidemiological trends and genetic dynamics of PRRSV in Vietnam, and will provide a theoretical 32 basis for formulating prevention and control measures for PRRS and the development of PRRS 33 vaccines.
Endoplasmic reticulum stress alters myelin associated protein expression and extracellular vesicle composition in human oligodendrocytes
Authors: Evalt Ethan D. , Govindaraj Saranraj , Jones Madison T. , Ozsoy Nesve , Chen Han , Russell Ashley E.
Published: October 2024

Myelination of the central nervous system is mediated by specialized glial cells called oligodendrocytes (OLs). Multiple sclerosis (MS) is characterized by loss of myelination and subsequent clinical symptoms that can severely impact the quality of life and mobility of those affected by the disease. The major protein components of myelin sheaths are synthesized in the endoplasmic reticulum (ER), and ER stress has been observed in patients with MS. Extracellular vesicles (EVs) have been shown to carry bioactive cargo and have the potential to be utilized as noninvasive biomarkers for various diseases. In the current study, we sought to determine how ER stress in OLs affected the production of key myelination proteins and EV release and composition. To achieve this, tunicamycin was used to induce ER stress in a human oligodendroglioma cell line and changes in myelination protein expression and markers of autophagy were assessed. EVs were also separated from the conditioned cell culture media through size exclusion chromatography and characterized. Significant reductions in the expression of myelination proteins and alterations to autophagosome formation were observed in cells undergoing ER stress. EVs released from these cells were slightly smaller relative to controls, and had strong expression of LC3B. We also observed significant upregulation of miR-29a-3p in ER stress EVs when compared to controls. Taken together, these data suggest that ER stress negatively impacts production of key myelination proteins and induces cells to release EVs that may function to preemptively activate autophagic pathways in neighboring cells.
Profiling genetic variants in cardiovascular disease genes among a Heterogeneous cohort of Mendelian conditions patients and electronic health records
Authors: Akawi Nadia , Al Mansoori Ghadeera , Al Zaabi Anwar , Badics Andrea , Al Dhaheri Noura , Al Shamsi Aisha , Al Tenaiji Amal , Alzohily Bashar , Almesmari Fatmah S. A. , Al Hammadi Hamad , Al Dhahouri Nahid , Irshaid Manal , Kizhakkedath Praseetha , Al Shibli Fatema , Tabouni Mohammed , Allam Mushal , Baydoun Ibrahim , Alblooshi Hiba , Ali Bassam R. , Foo Roger S. , Al Jasmi Fatma
Published: October 2024

Introduction

This study addresses the rising cardiovascular disease (CVD) rates in the United Arab Emirates (UAE) by investigating the occurrence and impact of genetic variants in CVD-related genes.

Methods

We collected all genes linked to heritable CVD from public and diagnostic databases and mapped them to their corresponding biological processes and molecular pathways. We then evaluated the types and burden of genetic variants within these genes in 343 individuals from the Emirati Mendelian Study Cohort and 3,007 national electronic health records.

Results

We identified a total of 735 genes associated with heritable CVD, covering a range of cardiovascular conditions. Enrichment analysis revealed key biological processes and pathways, including Apelin, FoxO, and Ras signaling, that are implicated across all forms of heritable CVD. Analysis of a UAE cohort of 3,350 individuals showed a predominance of rare and unique CVD variants specific to the population. The study found a significant burden of pathogenic variants in families with CVD within the Emirati Mendelian cohort and re-assessed the pathogenicity of 693 variants from national health records, leading to the discovery of new CVD-causing variants.

Discussion

This study underscores the importance of continuously updating our understanding of genes and pathways related to CVD. It also highlights the significant underrepresentation of the UAE population in public databases and clinical literature on CVD genetics, offering valuable insights that can inform future research and intervention strategies.