bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioformulation of Bacillus proteolyticus MITWPUB1 and its biosurfactant to control the growth of phytopathogen Sclerotium rolfsii for the crop Brassica juncea var local, as a sustainable approach
Authors: Mukadam Humaira , Gaikwad Shikha V. , Kutty Nithya N. , Gaikwad Vikrant D.
Published: April 2024

Bacillus proteolyticus MITWPUB1 is a potential producer of biosurfactants (BSs), and the organism is also found to be a producer of plant growth promoting traits, such as hydrogen cyanide and indole acetic acid (IAA), and a solubilizer of phosphate. The BSs were reportedly a blend of two classes, namely glycolipids and lipopeptides, as found by thin layer chromatography and Fourier-transform infrared spectroscopy analysis. Furthermore, semi-targeted metabolite profiling via liquid chromatography mass spectroscopy revealed the presence of phospholipids, lipopeptides, polyamines, IAA derivatives, and carotenoids. The BS showed dose-dependent antagonistic activity against Sclerotium rolfsii; scanning electron microscopy showed the effects of the BS on S. rolfsii in terms of mycelial deformations and reduced branching patterns. In vitro studies showed that the application of B. proteolyticus MITWPUB1 and its biosurfactant to seeds of Brassica juncea var local enhanced the seed germination rate. However, sawdust-carrier-based bioformulation with B. proteolyticus MITWPUB1 and its BS showed increased growth parameters for B. juncea var L. This study highlights a unique bioformulation combination that controls the growth of the phytopathogen S. rolfsii and enhances the plant growth of B. juncea var L. Bacillus proteolyticus MITWPUB1 was also shown for the first time to be a prominent BS producer with the ability to control the growth of the phytopathogen S. rolfsii.
Qualitative and quantitative chemical analysis of Leptadenia hastata: exploring a traditional african medicinal plant
Authors: Zhang Jiangsheng , Nan Yi , Su Jie , Jibril Aminu Usman , Lv Guiyuan
Published: April 2024

Leptadenia hastata (Pers.) Decne is a commonly used food source and prescribed as a traditional African medicine for treatment of various diseases, such as diabetes, skin disorders, wounds, and ulcers. However, quality control has become a bottleneck restricting the therapeutic development and utilization of this plant. In this study, a reliable method for qualitative and quantitative determination of components in Leptadenia hastata was established. The components of L. hastata were profiled using ultra-high performance liquid chromatography coupled with quadruple time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS). Subsequently, an ultra-high performance tandem diode array detector (UHPLC-DAD)-based method was used for simultaneous quantitative analysis of five major constituents in six batches of L. hastata samples. As a result, 35 compounds were tentatively identified. The quantities of the five constituents (vicenin-Ⅱ, orientin, schaftoside, chrysin 6-C-arabinoside 8-C-glucoside, chrysin 6-C-glucoside 8-C-arabinoside) were determined as 124.8–156.9 μg/g, 170.5–216.0 μg/g, 61.31–93.73 μg/g, 85.13–119.3 μg/g and 99.82–129.4 μg/g, respectively. This method offers a successful strategy for precise and effective evaluation of the constituents of L. hastata, providing a robust foundation for holistic quality assessment of medicinal plants.
Yeast species in the respiratory samples of COVID-19 patients; molecular tracking of Candida auris
Authors: Rouhi Faezeh , Soltani Sajedeh , Sadeghi Somayeh , Nasri Elahe , Hosseini Mahnaz , Ghafel Safiyeh , Aboutalebian Shima , Fakhim Hamed , Mirhendi Hossein
Published: April 2024

Introduction

Although the existence of Candida species in the respiratory tract is often considered commensal, it is crucial to recognize the significance of Candida colonization in immunocompromised or COVID-19 patients. The emergence of Candida auris as an emerging pathogen further emphasizes the importance of monitoring yeast infection/colonization, particularly in COVID-19 patients.

Methods

In this study, respiratory samples mainly from COVID-19 patients, primarily those suspected of having a fungal infection, were cultured on Sabouraud dextrose agar plates and the yeast colonies were identified using a two-step multiplex PCR method. The samples suspected of C. auris underwent specific nested PCR followed by sequence analysis.

Results

A total of 199 respiratory samples were collected from 73 women and 126 men, ranging in age from 1.6 to 88 years. Among the patients, 141 had COVID-19, 32 had cancer, 5 were hospitalized in ICU, 2 had chronic obstructive pulmonary disease)COPD(, and others were patients with combination diseases. From these samples, a total of 334 yeast strains were identified. C. albicans (n=132, 39.52%) was the most common species, followed by C. tropicalis (n=67, 20%), C. glabrata (n=56, 16.76%), C. krusei (n=18, 5.4%), C. parapsilosis (n=17, 5.08%), Saccharomyces cerevisiae (n=10, 3%), C. kefyr (n=9, 2.6%), C. dubliniensis (n=7, 2.1%), C. lusitaniae (n=5, 1.5%), C. auris (n=3, 0.9%), C. guilliermondii (n=2, 0.6%), C. rugosa (n=1, 0.3%), C. intermedia (n=1, 0.3%), and Trichosporon spp. (n=1, 0.3%). C. auris was detected in a patient in ICU and two COVID-19 patients. While its presence was confirmed through sequence analysis, our extensive efforts to isolate C. auris were unsuccessful.

Conclusion

While C. albicans colonization remains prevalent, our study found no evidence of Candida lung infection. Since the role of Candida colonization in airway secretions remains ambiguous due to limited research, further studies are imperative to shed light on this matter.
Uncovering specific taxonomic and functional alteration of gut microbiota in chronic kidney disease through 16S rRNA data
Authors: Zhang Yangyang , Zhong Weicong , Liu Wenting , Wang Xiaohua , Lin Gan , Lin Jiawen , Fang Junxuan , Mou Xiangyu , Jiang Shan , Huang Jiayuan , Zhao Wenjing , Zheng Zhihua
Published: April 2024

Introduction

Chronic kidney disease (CKD) is worldwide healthcare burden with growing incidence and death rate. Emerging evidence demonstrated the compositional and functional differences of gut microbiota in patients with CKD. As such, gut microbial features can be developed as diagnostic biomarkers and potential therapeutic target for CKD.

Methods

To eliminate the outcome bias arising from factors such as geographical distribution, sequencing platform, and data analysis techniques, we conducted a comprehensive analysis of the microbial differences between patients with CKD and healthy individuals based on multiple samples worldwide. A total of 980 samples from six references across three nations were incorporated from the PubMed, Web of Science, and GMrepo databases. The obtained 16S rRNA microbiome data were subjected to DADA2 processing, QIIME2 and PICRUSt2 analyses.

Results

The gut microbiota of patients with CKD differs significantly from that of healthy controls (HC), with a substantial decrease in the microbial diversity among the CKD group. Moreover, a significantly reduced abundance of bacteria Faecalibacterium prausnitzii (F. prausnitzii) was detected in the CKD group through linear discriminant analysis effect size (LEfSe) analysis, which may be associated with the alleviating effects against CKD. Notably, we identified CKD-depleted F. prausnitzii demonstrated a significant negative correlation with three pathways based on predictive functional analysis, suggesting its potential role in regulating systemic acidbase disturbance and pro-oxidant metabolism.

Discussion

Our findings demonstrated notable alterations of gut microbiota in CKD patients. Specific gut-beneficial microbiota, especially F. prausnitzii, may be developed as a preventive and therapeutic tool for CKD clinical management.
Insights into the molecular phylogeny and morphology of three novel Dothiora species, along with a worldwide checklist of Dothiora
Authors: Senwanna Chanokned , Hongsanan Sinang , Khuna Surapong , Kumla Jaturong , Yarasheva Manzura , Gafforov Yusufjon , Abdurazakov Aziz , Suwannarach Nakarin
Published: April 2024

Most species of Dothiora are known from the dead parts of various host plants as saprobic fungi in terrestrial habitats occurring in tropical and temperate regions. In the present study, samples of Dothiora were collected from dead twigs and branches of Capparis spinosa, Rhaponticum repens, and an unknown angiosperm plant from the Tashkent and Jizzakh regions of Uzbekistan. Multi-gene phylogenetic analyses based on a combined ITS, LSU, SSU, TEF1, and TUB2 sequence data revealed their taxonomic positions within the Dothideaceae. Three new species of Dothiora, namely, Dothiora capparis, Dothiora rhapontici, and Dothiora uzbekistanica were proposed by molecular and morphological data. Likewise, the phylogenetic relationship and morphology of Dothiora are discussed. In addition, we provide a list of accepted Dothiora species, including host information, distribution, morphology descriptions, and availability of sequence data, to enhance the current knowledge of the diversity within Dothiora.
Understanding L2 generalist teachers' motivation for teaching EFL in China's rural elementary schools
Authors: Sun Wei , Shi Hong
Published: April 2024

In the context of global mandates for English as a Foreign Language (EFL) education, rural regions face significant hurdles in delivering high-quality language instruction. Generalist teachers in these areas often lack specialized training in EFL, yet are tasked with its instruction. Referred to as L2 generalists, these educators hold a pivotal role in EFL education. However, a notable gap exists in understanding the motivation propelling generalist teachers to undertake EFL instruction, particularly within Chinese rural primary schools, where various challenges persist. Grounded in self-discrepancy theory and possible selves theory, this study examined the way L2 generalist teachers' teaching motivation linked to their various self-concepts as well as their responses to various challenges when delivering EFL teaching in rural elementary schools in China. The study uncovered that the alignment between L2 generalist teachers' ought selves (i.e., the selves that they believe they should be) and ideal selves (i.e., the selves they aspire to become) acted as motivating factors, guiding their active involvement in EFL teaching. However, challenges such as a lack of professionalization and high contextual expectations led to a discrepancy between their actual selves (i.e., the selves they perceive themselves to currently be) and their ought/ideal selves, diminishing their teaching motivation. Furthermore, the presence of ambiguous and conflicting school policies further complicated matters, confusing generalist teachers and eroding their motivation for teaching. Despite experiencing a decline in motivation for EFL teaching, their commitment to their students fostered consistency between their ideal and ought selves, inspiring them to innovate pedagogical strategies within their capabilities. The study's findings hold significance for policymakers and teacher educators, highlighting the necessity of implementing strategies to enhance the professional growth of rural L2 generalist teachers.
Transcriptional profiles associated with coronary artery disease in type 2 diabetes mellitus
Authors: Nevado Jose B. , Cutiongco-de la Paz Eva Maria C. , Paz-Pacheco Elizabeth T. , Jasul Gabriel V. , Aman Aimee Yvonne Criselle L. , Deguit Christian Deo T. , San Pedro Jana Victoria B. , Francisco Mark David G.
Published: April 2024

Background

Coronary artery disease (CAD) is a common complication of Type 2 diabetes mellitus (T2DM). Understanding the pathogenesis of this complication is essential in both diagnosis and management. Thus, this study aimed to characterize the presence of CAD in T2DM using molecular markers and pathway analyses.

Methods

The study is a sex- and age-frequency matched case-control design comparing 23 unrelated adult Filipinos with T2DM-CAD to 23 controls (DM with CAD). Healthy controls served as a reference. Total RNA from peripheral blood mononuclear cells (PBMCs) underwent whole transcriptomic profiling using the Illumina HumanHT-12 v4.0 expression beadchip. Differential gene expression with gene ontogeny analyses was performed, with supporting correlational analyses using weighted correlation network analysis (WGCNA).

Results

The study observed that 458 genes were differentially expressed between T2DM with and without CAD (FDR<0.05). The 5 top genes the transcription factor 3 (TCF3), allograft inflammatory factor 1 (AIF1), nuclear factor, interleukin 3 regulated (NFIL3), paired immunoglobulin-like type 2 receptor alpha (PILRA), and cytoskeleton-associated protein 4 (CKAP4) with AUCs >89%. Pathway analyses show differences in innate immunity activity, which centers on the myelocytic (neutrophilic/monocytic) theme. SNP-module analyses point to a possible causal dysfunction in innate immunity that triggers the CAD injury in T2DM.

Conclusion

The study findings indicate the involvement of innate immunity in the development of T2DM-CAD, and potential immunity markers can reflect the occurrence of this injury. Further studies can verify the mechanistic hypothesis and use of the markers.
Exploration beyond osteoarthritis: the association and mechanism of its related comorbidities
Authors: Li Bo , Yang Zhenguo , Li Yang , Zhang Jiuchao , Li Chengen , Lv Naishan
Published: April 2024

Osteoarthritis is the most prevalent age-related degenerative joint disease and a leading cause of pain and disability in aged people. Its etiology is multifaceted, involving factors such as biomechanics, pro-inflammatory mediators, genetics, and metabolism. Beyond its evident impact on joint functionality and the erosion of patients’ quality of life, OA exhibits symbiotic relationships with various systemic diseases, giving rise to various complications. This review reveals OA’s extensive impact, encompassing osteoporosis, sarcopenia, cardiovascular diseases, diabetes mellitus, neurological disorders, mental health, and even cancer. Shared inflammatory processes, genetic factors, and lifestyle elements link OA to these systemic conditions. Consequently, recognizing these connections and addressing them offers opportunities to enhance patient care and reduce the burden of associated diseases, emphasizing the need for a holistic approach to managing OA and its complications.
Dissecting the shared genetic architecture between Alzheimer’s disease and frailty: a cross-trait meta-analyses of genome-wide association studies
Authors: Enduru Nitesh , Fernandes Brisa S. , Zhao Zhongming
Published: April 2024

Introduction: Frailty is the most common medical condition affecting the aging population, and its prevalence increases in the population aged 65 or more. Frailty is commonly diagnosed using the frailty index (FI) or frailty phenotype (FP) assessments. Observational studies have indicated the association of frailty with Alzheimer’s disease (AD). However, the shared genetic and biological mechanism of these comorbidity has not been studied.

Methods: To assess the genetic relationship between AD and frailty, we examined it at single nucleotide polymorphism (SNP), gene, and pathway levels.

Results: Overall, 16 genome-wide significant loci (15 unique loci) (pmeta-analysis < 5 × 10−8) and 22 genes (21 unique genes) were identified between AD and frailty using cross-trait meta-analysis. The 8 shared loci implicated 11 genes: CLRN1-AS1, CRHR1, FERMT2, GRK4, LINC01929, LRFN2, MADD, RP11-368P15.1, RP11-166N6.2, RNA5SP459, and ZNF652 between AD and FI, and 8 shared loci between AD and FFS implicated 11 genes: AFF3, C1QTNF4, CLEC16A, FAM180B, FBXL19, GRK4, LINC01104, MAD1L1, RGS12, ZDHHC5, and ZNF521. The loci 4p16.3 (GRK4) was identified in both meta-analyses. The colocalization analysis supported the results of our meta-analysis in these loci. The gene-based analysis revealed 80 genes between AD and frailty, and 4 genes were initially identified in our meta-analyses: C1QTNF4, CRHR1, MAD1L1, and RGS12. The pathway analysis showed enrichment for lipoprotein particle plasma, amyloid fibril formation, protein kinase regulator, and tau protein binding.

Conclusion: Overall, our results provide new insights into the genetics of AD and frailty, suggesting the existence of non-causal shared genetic mechanisms between these conditions.
Use of whole-genome sequence data for fine mapping and genomic prediction of sea louse resistance in Atlantic salmon
Authors: Onabanjo Olumide , Meuwissen Theo , Aslam Muhammad Luqman , Schmitt Armin Otto , Dagnachew Binyam
Published: April 2024

Sea louse (Lepeophtheirus salmonis) infestation of Atlantic salmon (Salmo salar) is a significant challenge in aquaculture. Over the years, this parasite has developed immunity to medicinal control compounds, and non-medicinal control methods have been proven to be stressful, hence the need to study the genomic architecture of salmon resistance to sea lice. Thus, this research used whole-genome sequence (WGS) data to study the genetic basis of the trait since most research using fewer SNPs did not identify significant quantitative trait loci. Mowi Genetics AS provided the genotype (50 k SNPs) and phenotype data for this research after conducting a sea lice challenge test on 3,185 salmon smolts belonging to 191 full-sib families. The 50 k SNP genotype was imputed to WGS using the information from 197 closely related individuals with sequence data. The WGS and 50 k SNPs of the challenged population were then used to estimate genetic parameters, perform a genome-wide association study (GWAS), predict genomic breeding values, and estimate its accuracy for host resistance to sea lice. The heritability of host resistance to sea lice was estimated to be 0.21 and 0.22, while the accuracy of genomic prediction was estimated to be 0.65 and 0.64 for array and WGS data, respectively. In addition, the association test using both array and WGS data did not identify any marker associated with sea lice resistance at the genome-wide level. We conclude that sea lice resistance is a polygenic trait that is moderately heritable. The genomic predictions using medium-density SNP genotyping array were equally good or better than those based on WGS data.
A novel cis-regulatory element regulates αD and αA-globin gene expression in chicken erythroid cells
Authors: Cortés-Fernández de Lara Josué , Núñez-Martínez Hober Nelson , Tapia-Urzúa Gustavo , Garza-Manero Sylvia , Peralta-Alvarez Carlos Alberto , Furlan-Magaril Mayra , González-Buendía Edgar , Escamilla-Del-Arenal Martín , Casasola Andrea , Guerrero Georgina , Recillas-Targa Felix
Published: April 2024

Background

Cis-regulatory elements (CREs) play crucial roles in regulating gene expression during erythroid cell differentiation. Genome-wide erythroid-specific CREs have not been characterized in chicken erythroid cells, which is an organism model used to study epigenetic regulation during erythropoiesis.

Methods

Analysis of public genome-wide accessibility (ATAC-seq) maps, along with transcription factor (TF) motif analysis, CTCF, and RNA Pol II occupancy, as well as transcriptome analysis in fibroblasts and erythroid HD3 cells, were used to characterize erythroid-specific CREs. An α-globin CRE was identified, and its regulatory activity was validated in vitro and in vivo by luciferase activity and genome-editing assays in HD3 cells, respectively. Additionally, circular chromosome conformation capture (UMI-4C) assays were used to distinguish its role in structuring the α-globin domain in erythroid chicken cells.

Results

Erythroid-specific CREs displayed occupancy by erythroid TF binding motifs, CTCF, and RNA Pol II, as well as an association with genes involved in hematopoiesis and cell differentiation. An α-globin CRE, referred to as CRE-2, was identified as exhibiting enhancer activity over αD and αA genes in vitro and in vivo. Induction of terminal erythroid differentiation showed that α-globin CRE-2 is required for the induction of αD and αA. Analysis of TF binding motifs at α-globin CRE-2 shows apparent regulation mediated by GATA-1, YY1, and CTCF binding.

Conclusion

Our findings demonstrate that cell-specific CREs constitute a key mechanism that contributes to the fine-tuning gene regulation of erythroid cell differentiation and provide insights into the annotation and characterization of CREs in chicken cells.
ChestBioX-Gen: contextual biomedical report generation from chest X-ray images using BioGPT and co-attention mechanism
Authors: Ouis Mohammed Yasser , Akhloufi Moulay A.
Published: April 2024

Efficient and accurate radiology reporting is critical in modern healthcare for timely diagnosis and patient care. In this paper, we present a novel deep learning approach that leverages BioGPT and co-attention mechanisms for automatic chest X-ray report generation. Our model, termed “ChestBioX-Gen” is designed to bridge the gap between medical images and textual reports. BioGPT, a biological language model, contributes its contextual understanding to the task, while the co-attention mechanism efficiently aligns relevant regions of the image with textual descriptions. This collaborative combination enables ChestBioX-Gen to generate coherent and contextually accurate reports that embed complex medical findings. Our model not only reduces the burden on radiologists but also enhances the consistency and quality of reports. By automating the report generation process, ChestBioX-Gen contributes to faster diagnoses and improved patient care. Quantitative evaluations, measured through BLEU-N and Rouge-L metrics, demonstrate the model's proficiency in producing clinically relevant reports with scores of 0.6685, 0.6247, 0.5689, 0.4806, and 0.7742 on BLUE 1, 2, 3, 4, and Rouge-L, respectively. In conclusion, the integration of BioGPT and co-attention mechanisms in ChestBioX-Gen represents an advancement in AI-driven medical image analysis. As radiology reporting plays a critical role in healthcare, our model holds the potential to revolutionize how medical insights are extracted and communicated, ultimately benefiting both radiologists and patients.
The non-pathogenic protozoon Leishmania tarentolae interferes with the activation of NLRP3 inflammasome in human cells: new perspectives in the control of inflammation
Authors: La Rosa Francesca , Varotto-Boccazzi Ilaria , Saresella Marina , Marventano Ivana , Cattaneo Giulia Maria , Hernis Ambra , Piancone Federica , Otranto Domenico , Epis Sara , Bandi Claudio , Clerici Mario
Published: April 2024

Background

Innate immune responses against infectious agents can act as triggers of inflammatory diseases. On the other hand, various pathogens have developed mechanisms for the evasion of the immune response, based on an inhibition of innate immunity and inflammatory responses. Inflammatory diseases could thus be controlled through the administration of pathogens or pathogen-derived molecules, capable of interfering with the mechanisms at the basis of inflammation. In this framework, the NLRP3 inflammasome is an important component in innate antimicrobial responses and a major player in the inflammatory disease. Parasites of the genus Leishmania are master manipulators of innate immune mechanisms, and different species have been shown to inhibit inflammasome formation. However, the exploitation of pathogenic Leishmania species as blockers of NLRP3-based inflammatory diseases poses safety concerns.

Methods

To circumvent safety issues associated with pathogenic parasites, we focused on Leishmania tarentolae, a species of Leishmania that is not infectious to humans. Because NLRP3 typically develops in macrophages, in response to the detection and engulfment microorganisms, we performed our experiments on a monocyte-macrophage cell line (THP-1), either wild type or knockout for ASC, a key component of NLRP3 formation, with determination of cytokines and other markers of inflammation.

Results

L. tarentolae was shown to possess the capability of dampening the formation of NLRP3 inflammasome and the consequent expression of pro-inflammatory molecules, with minor differences compared to effects of pathogenic Leishmania species.

Conclusion

The non-pathogenic L. tarentolae appears a promising pro-biotic microbe with anti-inflammatory properties or a source of immune modulating cellular fractions or molecules, capable of interfering with the formation of the NLRP3 inflammasome.
Fine-scale hunting strategies in Australian fur seals
Authors: Salzeri Perla , Luque Sebastián P. , Arnould John P. Y.
Published: April 2024

Introduction

Knowledge of the hunting strategies of top predators can provide insights into the cost-benefit trade-offs of their foraging activities. Air-breathing marine predators are constrained in their foraging activities due to their metabolic expenditure at depth being supported by limited body oxygen stores. Understanding how these species adapt their behaviours to maximise foraging success is of importance in view of the anticipated alterations to marine ecosystems in response to global change. The Australian fur seal (Arctocephalus pusillus doriferus), the largest fur seal species, has a distribution restricted to south-eastern Australia, which is one of the fastest warming oceanic regions and where the abundance, distribution and diversity of prey species is expected to change in coming decades.

Methods

In the present study, combined IMU (acceleration, magnetometer, gyroscope), depth and GPS data logger information was used to reconstruct 3-dimensional tracks during diving, assess energy expenditure and quantify prey capture events in adult female Australian fur seals during benthic foraging.

Results

The results revealed that individuals ascended at steeper pitches (to reduce transit time), remained for shorter durations and travelled shorter distances at the surface, and then descended at steeper pitches on subsequent dives after predatory events on the seafloor. Higher travel speeds and more directional changes during searching for prey along the seafloor, while requiring greater energy expenditure, were associated with more prey captures. Interestingly, individuals did not display conventional Area Restricted Search, with the heading between dives not influenced by prey encounters.

Discussion

Together, these results suggest Australian fur seals undertake rapid searching along the seafloor to surprise cryptic prey and, if prey is encountered, undertake rapid surfacing (to reload body oxygen stores) and return to nearby seafloor habitat with a similar but undisturbed prey field.
Model-based performance study of an industrial single spool gas turbine 9EA-GT by changing the inlet guide vane angle and modifying the compressor map
Authors: Alblawi Adel
Published: April 2024

In this article, an industrial gas turbine engine with a single spool (single spool 9EA-GT) is discussed, and a thermodynamic model for computing steady-state performance is presented. In addition, a novel component map production method for investigating a gas turbine engine (GTE) is developed for a different compressor and turbine by downloading from the GasTurb 12 tool and scaling to the compressor and turbine’s design points. A system of controlling engine flow capacitance by changing inlet guide vanes (IGVs) is presented. Adjusting the controllable IGV blades can optimize all the engine units by continuously correcting the compressor features map. The airflow via the compressor, which in turn controls the airflow throughout the entire system, is managed by IGVs. The computations for steady-state performance involve two models: steady-state behavior at engine startup (from 65% to 100% speed, without load) and steady-state behavior while loading (continuous speed of 100%). In this model, the challenges brought by the lack of understanding of stage-by-stage performance are resolved by building artificial machine maps using suitable scaling methods to generalized maps derived from the previous research and validating them with experimental observations from real power plants. The engine performance simulation utilizing the maps is carried out using MATLAB. Assessment results are found to be in good agreement with the actual performance data. During a steady start, the control system used in this study decreased the fuel consumption, exhaust gas mass flow rate, and compressor-driven power for the GTE by 9.5%, 19.3%, and 37.5%, respectively, and those variables decreased by 1%, 12.2%, and 19.7%, respectively, when loading the engine.
Neuroanatomical correlates of distracted straight driving performance: a driving simulator MRI study across the lifespan
Authors: Guan Dylan X. , Churchill Nathan W. , Fischer Corinne E. , Graham Simon J. , Schweizer Tom A.
Published: April 2024

Background

Driving is the preferred mode of transportation for adults across the healthy age span. However, motor vehicle crashes are among the leading causes of injury and death, especially for older adults, and under distracted driving conditions. Understanding the neuroanatomical basis of driving may inform interventions that minimize crashes. This exploratory study examined the neuroanatomical correlates of undistracted and distracted simulated straight driving.

Methods

One-hundred-and-thirty-eight participants (40.6% female) aged 17–85 years old (mean and SD = 58.1 ± 19.9 years) performed a simulated driving task involving straight driving and turns at intersections in a city environment using a steering wheel and foot pedals. During some straight driving segments, participants responded to auditory questions to simulate distracted driving. Anatomical T1-weighted MRI was used to quantify grey matter volume and cortical thickness for five brain regions: the middle frontal gyrus (MFG), precentral gyrus (PG), superior temporal cortex (STC), posterior parietal cortex (PPC), and cerebellum. Partial correlations controlling for age and sex were used to explore relationships between neuroanatomical measures and straight driving behavior, including speed, acceleration, lane position, heading angle, and time speeding or off-center. Effects of interest were noted at an unadjusted p-value threshold of 0.05.

Results

Distracted driving was associated with changes in most measures of straight driving performance. Greater volume and cortical thickness in the PPC and cerebellum were associated with reduced variability in lane position and heading angle during distracted straight driving. Cortical thickness of the MFG, PG, PPC, and STC were associated with speed and acceleration, often in an age-dependent manner.

Conclusion

Posterior regions were correlated with lane maintenance whereas anterior and posterior regions were correlated with speed and acceleration, especially during distracted driving. The regions involved and their role in straight driving may change with age, particularly during distracted driving as observed in older adults. Further studies should investigate the relationship between distracted driving and the aging brain to inform driving interventions.
Practical tool to identify Spasticity-Plus Syndrome amongst patients with multiple sclerosis. Algorithm development based on a conjoint analysis
Authors: Fernández Fernández Óscar , Costa-Frossard Lucienne , Martínez Ginés Maria Luisa , Montero Escribano Paloma , Prieto González José María , Ramió-Torrentà Lluís , Aladro Yolanda , Alonso Torres Ana , Álvarez Rodríguez Elena , Labiano-Fontcuberta Andrés , Landete Pascual Lamberto , Miralles Martínez Ambrosio , Moral Torres Ester , Oliva-Nacarino Pedro
Published: April 2024

Introduction

The Spasticity-Plus Syndrome (SPS) in multiple sclerosis (MS) refers to a combination of spasticity and other signs/symptoms such as spasms, cramps, bladder dysfunction, tremor, sleep disorder, pain, and fatigue. The main purpose is to develop a user-friendly tool that could help neurologists to detect SPS in MS patients as soon as possible.

Methods

A survey research based on a conjoint analysis approach was used. An orthogonal factorial design was employed to form 12 patient profiles combining, at random, the eight principal SPS signs/symptoms. Expert neurologists evaluated in a survey and a logistic regression model determined the weight of each SPS sign/symptom, classifying profiles as SPS or not.

Results

72 neurologists participated in the survey answering the conjoint exercise. Logistic regression results of the survey showed the relative contribution of each sign/symptom to the classification as SPS. Spasticity was the most influential sign, followed by spasms, tremor, cramps, and bladder dysfunction. The goodness of fit of the model was appropriate (AUC = 0.816). Concordance between the experts’ evaluation vs. model estimation showed strong Pearson’s (r = 0.936) and Spearman’s (r = 0.893) correlation coefficients. The application of the algorithm provides with a probability of showing SPS and the following ranges are proposed to interpret the results: high (> 60%), moderate (30–60%), or low (< 30%) probability of SPS.

Discussion

This study offers an algorithmic tool to help healthcare professionals to identify SPS in MS patients. The use of this tool could simplify the management of SPS, reducing side effects related with polypharmacotherapy.
Single-voxel delay map from long-axial field-of-view PET scans
Authors: Nielsen Frederik Bay , Lindberg Ulrich , Bordallo Heloisa N. , Johnbeck Camilla Bardram , Law Ian , Fischer Barbara Malene , Andersen Flemming Littrup , Andersen Thomas Lund
Published: April 2024

Objective

We present an algorithm to estimate the delay between a tissue time-activity curve and a blood input curve at a single-voxel level tested on whole-body data from a long-axial field-of-view scanner with tracers of different noise characteristics.

Methods

Whole-body scans of 15 patients divided equally among three tracers, namely [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, which were used in development and testing of the algorithm. Delay times were estimated by fitting the cumulatively summed input function and tissue time-activity curve with special considerations for noise. To evaluate the performance of the algorithm, it was compared against two other algorithms also commonly applied in delay estimation: name cross-correlation and a one-tissue compartment model with incorporated delay. All algorithms were tested on both synthetic time-activity curves produced with the one-tissue compartment model with increasing levels of noise and delays between the tissue activity curve and the blood input curve. Whole-body delay maps were also calculated for each of the three tracers with data acquired on a long-axial field-of-view scanner with high time resolution.

Results

Our proposed model performs better for low signal-to-noise ratio time-activity curves compared to both cross-correlation and the one-tissue compartment models for non-[15O]H2O tracers. Testing on synthetically produced time-activity curves showed only a small and even residual delay, while the one-tissue compartment model with included delay showed varying residual delays.

Conclusion

The algorithm is robust to noise and proves applicable on a range of tracers as tested on [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, and hence is a viable option offering the ability for delay correction across various organs and tracers in use with kinetic modeling.
The coexistence of myosteatosis and the creatinine/cystatin C ratio are determinants of outcomes in cholangiocarcinoma patients undergoing curative surgery
Authors: Liu Yan , Zhang Jingli , Song Guanghui , Ding Xueli , Sun Hui , Zhou Jianrui , Jing Xue
Published: April 2024

Background

Myosteatosis is a well-established predictor of poor prognosis in many types of cancer, and a decreased Creatinine/Cystatin C ratio (CCR) is a known indicator of unfavorable outcomes in patients with metabolic disorders and cancer. Despite this knowledge, the significance of concurrent CCR and myosteatosis in predicting the prognosis of patients with cholangiocarcinoma (CCA) who undergo radical surgery remains uncertain.

Method

Data from 757 patients with cholangiocarcinoma who underwent the first radical resection in the Affiliated Hospital of Qingdao University from January 2017 to March 2022 were collected. According to the inclusion and exclusion criteria, 149 patients were finally included in the retrospective study cohort. Various clinicopathological, serological, and radiological data were collected at admission. Myosteatosis was evaluated using sliceOmatic software on computed tomography (CT) images. The study used receiver operating characteristic (ROC) curve analysis to determine the critical value of CCR, which predicts overall survival (OS) based on the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were employed to identify the risk factors associated with OS and RFS confidently.

Results

The group identified as the myosteatosis cohort consisted of 79 patients with an average age of 64.3 ± 7.8 years. The ROC curve analysis revealed an optimal critical CCR value of 10.834. A low CCR ≤ 10.834 and myosteatosis were found to be associated with poor OS and RFS outcomes (P = 0.022; P = 0.017; P = 0.038; P = 0.030 respectively). Moreover, patients with myosteatosis and a CCR ≤ 10.834 had the worst OS and RFS outcomes (P = 0.035; P = 0.027).

Conclusion

After radical excision in CCA patients, the presence of myosteatosis and CCR had a negative correlation with prognosis. A more accurate prediction of OS and RFS was possible by combining CCR and myosteatosis, compared to CCR alone.
The use of technology in cancer prehabilitation: a systematic review
Authors: Tay San San , Zhang Fuquan , Neo Edmund Jin Rui
Published: April 2024

Aim

This review aimed to evaluate the effectiveness and feasibility of cancer prehabilitation programs delivered through technological enablers compared to conventional face-to-face interventions.

Methods

A systematic review was conducted, searching PubMed, Embase, and CINAHL for studies published from inception to February 6, 2024. Studies were included if they involved adult cancer patients in primary research, utilized technology for prehabilitation, and assessed functional, psychological, and quality of life outcomes.

Results

Sixteen studies were included, encompassing wearables, apps, teleprehabilitation, and virtual reality. All studies reported feasibility, but challenges included technical issues, lack of supervision, and non-compliance. Effectiveness depended on intervention rigor and technology type. Wearables offered objective monitoring but faced compliance issues. Videoconferencing provided supervision and could mitigate compliance concerns. Multimodal programs and intervention-specific outcome measures were recommended.

Conclusion

Technology-based prehabilitation programs seem feasible, but effectiveness depends on intervention design and technology employed. Future research should focus on developing robust evidence to guide clinical practice and explore the potential of integrated technological solutions.

Systematic review registration

PROSPERO, identifier CRD42022376028.
An invasion front gene expression signature for higher-risk patient selection in stage IIA MSS colon cancer
Authors: Budinská Eva , Čarnogurská Martina , Ivković Tina Catela , Macháčková Táňa , Boudná Marie , Pifková Lucie , Slabý Ondřej , Bencsiková Beatrix , Popovici Vlad
Published: April 2024

Stage II colon cancer (CC) encompasses a heterogeneous group of patients with diverse survival experiences: 87% to 58% 5-year relative survival rates for stages IIA and IIC, respectively. While stage IIA patients are usually spared the adjuvant chemotherapy, some of them relapse and may benefit from it; thus, their timely identification is crucial. Current gene expression signatures did not specifically target this group nor did they find their place in clinical practice. Since processes at invasion front have also been linked to tumor progression, we hypothesize that aside from bulk tumor features, focusing on the invasion front may provide additional clues for this stratification. A retrospective matched case-control collection of 39 stage IIA microsatellite-stable (MSS) untreated CCs was analyzed to identify prognostic gene expression-based signatures. The endpoint was defined as relapse within 5 years vs. no relapse for at least 6 years. From the same tumors, three different classifiers (bulk tumor, invasion front, and constrained baseline on bulk tumor) were developed and their performance estimated. The baseline classifier, while the weakest, was validated in two independent data sets. The best performing signature was based on invasion front profiles [area under the receiver operating curve (AUC) = 0.931 (0.815–1.0)] and contained genes associated with KRAS pathway activation, apical junction complex, and heme metabolism. Its combination with bulk tumor classifier further improved the accuracy of the predictions.
Case report: A case of recurrent cervical cancer with bronchial and esophageal metastases presenting with hemoptysis and dysphagia
Authors: Yu Xiao , Dong Shixiang , Wang Wenjie , Sun Xin , Wang Yankui , Yu Fengsheng
Published: April 2024

Background

The treatment outcomes and prognosis for recurrent cervical cancer are generally poor, with a 5-year survival rate of only 10%–20%.

Case presentation

In this case, the patient is a young woman who experienced a recurrence 5 years after the initial treatment of cervical cancer. Her primary symptoms were hemoptysis and dysphagia, indicative of hilar and mediastinal lymph node metastases, with further involvement of the bronchus and esophagus. Additionally, the patient also presented with tumor-associated dermatomyositis. Following combined treatment with albumin-bound paclitaxel, carboplatin, bevacizumab, and cadonilimab, the patient’s tumor was effectively controlled.
Tofacitinib to prevent anti-drug antibody formation against LMB-100 immunotoxin in patients with advanced mesothelin-expressing cancers
Authors: Skorupan Nebojsa , Peer Cody J. , Zhang Xianyu , Choo-Wosoba Hyoyoung , Ahmad Mehwish I. , Lee Min-Jung , Rastogi Shraddha , Sato Nahoko , Yu Yunkai , Pegna Guillaume Joe , Steinberg Seth M. , Kalsi Shelley S. , Cao Liang , Figg William D. , Trepel Jane B. , Pastan Ira , FitzGerald David , Alewine Christine
Published: April 2024

Background

LMB-100 is a mesothelin (MSLN)-targeting recombinant immunotoxin (iTox) carrying a Pseudomonas exotoxin A payload that has shown promise against solid tumors, however, efficacy is limited by the development of neutralizing anti-drug antibodies (ADAs). Tofacitinib is an oral Janus Kinase (JAK) inhibitor that prevented ADA formation against iTox in preclinical studies.

Methods

A phase 1 trial testing LMB-100 and tofacitinib in patients with MSLN-expressing cancers (pancreatic adenocarcinoma, n=13; cholangiocarcinoma, n=1; appendiceal carcinoma, n=1; cystadenocarcinoma, n=1) was performed to assess safety and to determine if tofacitinib impacted ADA formation. Participants were treated for up to 3 cycles with LMB-100 as a 30-minute infusion on days 4, 6, and 8 at two dose levels (100 and 140 µg/kg) while oral tofacitinib was administered for the first 10 days of the cycle (10 mg BID). Peripheral blood was collected for analysis of ADA levels, serum cytokines and circulating immune subsets.

Results

The study was closed early due to occurrence of drug-induced pericarditis in 2 patients. Pericarditis with the combination was not reproducible in a transgenic murine model containing human MSLN. Two of 4 patients receiving all 3 cycles of treatment maintained effective LMB-100 levels, an unusual occurrence. Sustained increases in systemic IL-10 and TNF-α were seen, a phenomenon not observed in prior LMB-100 studies. A decrease in activated T cell subsets and an increase in circulating immunosuppressive myeloid populations occurred. No radiologic decreases in tumor volume were observed.

Discussion

Further testing of tofacitinib to prevent ADA formation is recommended in applicable non-malignant disease settings.

Clinical trial registration

https://www.clinicaltrials.gov/study/NCT04034238.
Da-Cheng-Qi decoction improves severe acute pancreatitis capillary leakage syndrome by regulating tight junction-associated proteins
Authors: Tu Jiamin , Jiang Yinping , Tu Lei , Chen Yafeng , Pan Liyun , Fan Xinjuan , Tian Jiyun , Li Jianguo , Wang Xinji , Fu Honghao , Xu Bing , Feng Dianxu
Published: April 2024

Background and aims:

To investigate mechanisms underlying the effects of Da-Cheng-Qi decoction (DCQD) on severe acute pancreatitis (SAP) capillary leakage syndrome.

Methods:

In this study, a SAP rat model was established using retrograde perfusion of 5% sodium taurocholate into the biliopancreatic duct. The study included three randomized groups: control, SAP (modeling), and DCQD (via gavage at 2 h pre-modeling and 2 and 4 h post-modeling). HPLC was used to analyzed major components of DCQD. Pathological changes and capillary permeability in the rat pancreatic tissues were examined. mRNA levels of claudin 5, occludin, zonula occludin-1 (ZO-1), and junctional adhesion molecules (JAM-C) were assessed using qRT-PCR. Tight junction-associated protein expression was evaluated using immunofluorescence and Western blot analyses. Human umbilical vein endothelial cells (HUVECs) were used to investigate the mechanism m of DCQD.

Results:

Serum levels of amylase, TNF–α, IL-1β, IL-2, and IL-6 were higher in the SAP group compared to the DCQD group (p < 0.05). DCQD treatment significantly attenuated rat pancreas damage (p < 0.05) and reduced tissue capillary permeability compared to the SAP group (p < 0.05). Claudin 5, occludin, and ZO-1 expression in the rat tissues was upregulated, but JAM-C was downregulated by DCQD treatment (p < 0.05). HUVEC permeability was improved by DCQD in a dose-time-dependent manner compared to the SAP group (p < 0.05). DCQD also upregulated claudin 5, occludin, and ZO-1 expression in vitro (p < 0.05).

Conclusion:

DCQD can improve capillary permeability in both in vivo and in vitro models of SAP by upregulating expression of claudin 5, occludin, and ZO-1, but not JAM-C.
Synthesis and biological evaluation of the novel chrysin prodrug for non-alcoholic fatty liver disease treatment
Authors: Zhang Ruiming , Gao Chuanyue , Hu Mingxing , Wang Xingxing , Li Shuoyuan , An Zhenmei , Yang Xifei , Xie Yongmei
Published: April 2024

Background: Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that has been reported as a potential treatment for non-alcoholic fatty liver disease (NAFLD). However, extensive phase II metabolism and poor aqueous solubility led to a decrease in the chrysin concentration in the blood after oral administration, limiting its pharmacological development in vivo.

Methods: In the present study, we synthesized a novel chrysin derivative prodrug (C-1) to address this issue. We introduced a hydrophilic prodrug group at the 7-position hydroxyl group, which is prone to phase II metabolism, to improve water solubility and mask the metabolic site. Further, we evaluated the ameliorative effects of C-1 on NAFLD in vitro and in vivo by NAFLD model cells and db/db mice.

Results:In vitro studies indicated that C-1 has the ability to ameliorate lipid accumulation, cellular damage, and oxidative stress in NAFLD model cells. In vivo experiments showed that oral administration of C-1 at a high dose (69.3 mg/kg) effectively ameliorated hyperlipidemia and liver injury and reduced body weight and liver weight in db/db mice, in addition to alleviating insulin resistance. Proteomic analysis showed that C-1 altered the protein expression profile in the liver and particularly improved the expression of proteins associated with catabolism and metabolism. Furthermore, in our preliminary pharmacokinetic study, C-1 showed favorable pharmacokinetic properties and significantly improved the oral bioavailability of chrysin.

Conclusion: Our data demonstrated that C-1 may be a promising agent for NAFLD therapy.