bluuebunny/crossref_metadata_2025 huggingface dataset:
Counteracting effects of nutrient composition (Si:N) on export flux under artificial upwelling
Authors: Baumann Moritz , Goldenberg Silvan Urs , Taucher Jan , Fernández-Méndez Mar , Ortiz Joaquin , Haussmann Jacqueline , Riebesell Ulf
Published: July 2023

To keep global warming below 1.5°C, technologies that remove carbon from the atmosphere will be needed. Ocean artificial upwelling of nutrient-rich water stimulates primary productivity and could enhance the biological carbon pump for natural CO2 removal. Its potential may depend on the Si availability in the upwelled water, which regulates the abundance of diatoms that are key carbon exporters. In a mesocosm experiment, we tested the effect of nutrient composition (Si relative to N) in artificially upwelled waters on export quantity and quality in a subtropical oligotrophic environment. Upwelling led to a doubling of exported particulate matter and increased C:N ratios to well beyond Redfield (9.5 to 11.1). High Si availability stimulated this carbon over-consumption further, resulting in a temporary ~5-fold increase in POC export and ~30% increase in C:N ratios compared to Si-scarce upwelling. Whilst the biogenic Si ballast of the export flux increased more than 3.5-fold over the Si:N gradient, these heavier particles did not sink faster. On the contrary, sinking velocity decreased considerably under high Si:N, most likely due to reduced particle size. Respiration rates remained similar across all treatments indicating that biogenic Si did not protect particles against microbial degradation. Si availability thus influenced key processes of the biological carbon pump in counteracting ways by increasing the export magnitude and associated C:N ratios but decreasing the efficiency of carbon transfer to depth. These opposing effects need to be considered when evaluating the potential of artificial upwelling as negative emission technology.
Field investigation on the impact of vehicle traffic on the vibration of ancient seawalls in Qiantang River
Authors: Zhu Shenming , Tu Xiaobing , Hu Min , Shi Li , Zhou Lei
Published: July 2023

To investigate the vibrational impact of vehicular traffic on the ancient Qiantang River seawall, on-site measurements of the seawall’s pulsation and forced vibrations under different vehicle speeds and axle loads were conducted. The acquired data were analyzed in the time domain, frequency domain, and 1/3 octave bands, revealing the time-frequency vibrational characteristics of the ancient seawall structure. The results indicate that the characteristic frequencies of the ancient seawall are 3 Hz and 10 Hz, with the primary frequency band of the structural vibrations induced by vehicular traffic ranging from 0 to 30 Hz. Vehicle traffic primarily caused vertical vibrations in the seawall structure, with along-dike horizontal vibrations being significantly higher than cross-dike vibrations. Based on the measurement results, an empirical relationship between the peak vibration velocity of the ancient seawall and variations in vehicle speed and axle load was established. It was found that, compared to axle load, increased vehicle speed had a more pronounced amplification effect on the structural vibrations of the ancient seawall. To ensure the vibrational safety of the ancient seawall relics, maximum vehicle speeds for different loading conditions of tri-axle trucks were provided based on vibration limits: for an axle load of 10 t, speeds should be below 34 km/h; for 11.52 t, below 24 km/h; for 13.04 t, below 20 km/h; and for 14.56 t, below 15 km/h.
Case report: Hepatic inflammatory pseudotumor-like follicular dendritic cell sarcoma: a rare case and review of the literature
Authors: Yan Shuai , Yue Zhiqiang , Zhang Peng , Yuan Liuxia , Wang Huixuan , Yin Fei , Ju Linglin , Chen Lin , Cai Weihua , Ni Yi , Wu Jinzhu
Published: July 2023

Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare subtype of follicular dendritic cell sarcoma (FDCS) that primarily occurs in the liver and spleen. The etiology of IPT-like FDCS is unknown, and it has nonspecific clinical manifestations, imaging performance and laboratory test results. Recently, a patient with IPT-like FDCS was admitted to our hospital because of abdominal distension and anemia. Over the past 3 years, the patient has been followed up after a liver mass was found in a physical examination. The lesion gradually enlarged and caused compression symptoms. In November 2022, a tumor with a diameter of approximately 20 cm was found in the right posterior lobe of the liver after abdominal enhanced Magnetic resonance imaging (MRI) in our hospital. Liver tumor biopsy before the operation revealed a large number of hyperplastic plasma cells and a small number of spindle cells, and the spindle cells were atypical. After a complete examination, the patient underwent liver resection. Pathology after surgery confirmed liver IPT-like FDCS.
Risk factors of emergency cesarean section in pregnant women with severe placenta accreta spectrum: a retrospective cohort study
Authors: Zhao Hu , Li Xin , Yang Shuqi , Liu Tianjiao , Zhan Jun , Zou Juan , Lin Changsheng , Li Yalan , Du Na , Xiao Xue
Published: July 2023

Introduction

Placenta accreta spectrum (PAS) may cause enormous and potentially life-threatening hemorrhage in the intrapartum and postpartum periods in emergency cesarean section. How to reduce the occurrence of emergency cesarean section in patients with severe PAS is the key to reducing the adverse outcomes of them. This study aimed to investigate the impact of emergency cesarean section on the perioperative outcomes of pregnant women with PAS and neonates, and also aimed to explore the risk factors of emergency cesarean section in pregnant women with PAS.

Materials and methods

A retrospective investigation was conducted among 163 pregnant women with severe PAS. Of these, 72 were subjected to emergency cesarean sections. Data on the perioperative characteristics of the mothers and neonates were collected. Multivariable linear regression analysis was used to detect associations between maternal and perioperative characteristics and volume of intraoperative bleeding. Binary logical regression was used to analyze the association between maternal preoperative characteristics and emergency cesarean section. Linear regression analysis is used to analyze the relationship between gestational age and emergency cesarean section.

Results

The risks of emergency cesarean section increase 98, 112, 124, and 62% when the pregnant women with PAS accompanied by GHD, ICP, more prior cesarean deliveries and more severe PAS type, respectively. Noteworthy, the risk of emergency cesarean section decreases 5% when pre-pregnancy BMI increases 1 kg/m2 (OR: 0.95; CI: 0.82, 0.98; p = 0.038). Moreover, there is no significant linear correlation between emergency cesarean section and gestational age.

Conclusion

GHD, ICP, multiple prior cesarean deliveries and severe PAS type may all increase the risk of emergency cesarean section for pregnant women with PAS, while high pre-pregnancy BMI may be a protective factor due to less activity level. For pregnant women with severe PAS accompanied by these high risk factors, more adequate maternal and fetal monitoring should be carried out in the third trimester to reduce the risk of emergency cesarean section.
Microcirculation-guided resuscitation in sepsis: the next frontier?
Authors: Damiani Elisa , Carsetti Andrea , Casarotta Erika , Domizi Roberta , Scorcella Claudia , Donati Abele , Adrario Erica
Published: July 2023

Microcirculatory dysfunction plays a key role in the pathogenesis of tissue dysoxia and organ failure in sepsis. Sublingual videomicroscopy techniques enable the real-time non-invasive assessment of microvascular blood flow. Alterations in sublingual microvascular perfusion were detected during sepsis and are associated with poor outcome. More importantly, sublingual videomicroscopy allowed to explore the effects of commonly applied resuscitative treatments in septic shock, such as fluids, vasopressors and inotropes, and showed that the optimization of macro-hemodynamic parameters may not be accompanied by an improvement in microvascular perfusion. This loss of “hemodynamic coherence,” i.e., the concordance between the response of the macrocirculation and the microcirculation, advocates for the integration of microvascular monitoring in the management of septic patients. Nonetheless, important barriers remain for a widespread use of sublingual videomicroscopy in the clinical practice. In this review, we discuss the actual limitations of this technique and future developments that may allow an easier and faster evaluation of the microcirculation at the bedside, and propose a role for sublingual microvascular monitoring in guiding and titrating resuscitative therapies in sepsis.
Susceptibility and plant immune control—a case of mycorrhizal strategy for plant colonization, symbiosis, and plant immune suppression
Authors: Enebe Matthew Chekwube , Erasmus Mariana
Published: July 2023

Plants and microbes (mycorrhizal fungi to be precise) have evolved together over the past millions of years into an association that is mutualist. The plants supply the fungi with photosynthates and shelter, while the fungi reciprocate by enhancing nutrient and water uptake by the plants as well as, in some cases, control of soil-borne pathogens, but this fungi–plant association is not always beneficial. We argue that mycorrhizal fungi, despite contributing to plant nutrition, equally increase plant susceptibility to pathogens and herbivorous pests' infestation. Understanding of mycorrhizal fungi strategies for suppressing plant immunity, the phytohormones involved and the signaling pathways that aid them will enable the harnessing of tripartite (consisting of three biological systems)—plant–mycorrhizal fungi–microbe interactions for promoting sustainable production of crops.
EVMP: enhancing machine learning models for synthetic promoter strength prediction by Extended Vision Mutant Priority framework
Authors: Yang Weiqin , Li Dexin , Huang Ranran
Published: July 2023

Introduction

In metabolic engineering and synthetic biology applications, promoters with appropriate strengths are critical. However, it is time-consuming and laborious to annotate promoter strength by experiments. Nowadays, constructing mutation-based synthetic promoter libraries that span multiple orders of magnitude of promoter strength is receiving increasing attention. A number of machine learning (ML) methods are applied to synthetic promoter strength prediction, but existing models are limited by the excessive proximity between synthetic promoters.

Methods

In order to enhance ML models to better predict the synthetic promoter strength, we propose EVMP(Extended Vision Mutant Priority), a universal framework which utilize mutation information more effectively. In EVMP, synthetic promoters are equivalently transformed into base promoter and corresponding k-mer mutations, which are input into BaseEncoder and VarEncoder, respectively. EVMP also provides optional data augmentation, which generates multiple copies of the data by selecting different base promoters for the same synthetic promoter.

Results

In Trc synthetic promoter library, EVMP was applied to multiple ML models and the model effect was enhanced to varying extents, up to 61.30% (MAE), while the SOTA(state-of-the-art) record was improved by 15.25% (MAE) and 4.03% (R2). Data augmentation based on multiple base promoters further improved the model performance by 17.95% (MAE) and 7.25% (R2) compared with non-EVMP SOTA record.

Discussion

In further study, extended vision (or k-mer) is shown to be essential for EVMP. We also found that EVMP can alleviate the over-smoothing phenomenon, which may contributes to its effectiveness. Our work suggests that EVMP can highlight the mutation information of synthetic promoters and significantly improve the prediction accuracy of strength. The source code is publicly available on GitHub: https://github.com/Tiny-Snow/EVMP.
A bibliometric analysis of the global impact of metaproteomics research
Authors: Ascandari AbdulAziz , Aminu Suleiman , Safdi Nour El Houda , El Allali Achraf , Daoud Rachid
Published: July 2023

Background

Metaproteomics is a subfield in meta-omics that is used to characterize the proteome of a microbial community. Despite its importance and the plethora of publications in different research area, scientists struggle to fully comprehend its functional impact on the study of microbiomes. In this study, bibliometric analyses are used to evaluate the current state of metaproteomic research globally as well as evaluate the specific contribution of Africa to this burgeoning research area. In this study, we use bibliometric analyses to evaluate the current state of metaproteomic research globally, identify research frontiers and hotspots, and further predict future trends in metaproteomics. The specific contribution of Africa to this research area was evaluated.

Methods

Relevant documents from 2004 to 2022 were extracted from the Scopus database. The documents were subjected to bibliometric analyses and visualization using VOS viewer and Biblioshiny package in R. Factors such as the trends in publication, country and institutional cooperation networks, leading scientific journals, author’s productivity, and keywords analyses were conducted. The African publications were ranked using Field-Weighted Citation Impact (FWCI) scores.

Results

A total of 1,138 documents were included and the number of publications increased drastically from 2004 to 2022 with more publications (170) reported in 2021. In terms of publishers, Frontiers in Microbiology had the highest number of total publications (62). The United States of America (USA), Germany, China, and Canada, together with other European countries were the most productive. Institution-wise, the Helmholtz Zentrum für Umweltforschung, Germany had more publications while Max Plank Institute had the highest total collaborative link strength. Jehmlich N. was the most productive author whereas Hettich RL had the highest h-index of 63. Regarding Africa, only 2.2% of the overall publications were from the continent with more publication outputs from South Africa. More than half of the publications from the continent had an FWCI score ≥ 1.

Conclusion

The scientific outputs of metaproteomics are rapidly evolving with developed countries leading the way. Although Africa showed prospects for future progress, this could only be accelerated by providing funding, increased collaborations, and mentorship programs.
Understanding structure-guided variant effect predictions using 3D convolutional neural networks
Authors: Ramakrishnan Gayatri , Baakman Coos , Heijl Stephan , Vroling Bas , van Horck Ragna , Hiraki Jeffrey , Xue Li C. , Huynen Martijn A.
Published: July 2023

Predicting pathogenicity of missense variants in molecular diagnostics remains a challenge despite the available wealth of data, such as evolutionary information, and the wealth of tools to integrate that data. We describe DeepRank-Mut, a configurable framework designed to extract and learn from physicochemically relevant features of amino acids surrounding missense variants in 3D space. For each variant, various atomic and residue-level features are extracted from its structural environment, including sequence conservation scores of the surrounding amino acids, and stored in multi-channel 3D voxel grids which are then used to train a 3D convolutional neural network (3D-CNN). The resultant model gives a probabilistic estimate of whether a given input variant is disease-causing or benign. We find that the performance of our 3D-CNN model, on independent test datasets, is comparable to other widely used resources which also combine sequence and structural features. Based on the 10-fold cross-validation experiments, we achieve an average accuracy of 0.77 on the independent test datasets. We discuss the contribution of the variant neighborhood in the model’s predictive power, in addition to the impact of individual features on the model’s performance. Two key features: evolutionary information of residues in the variant neighborhood and their solvent accessibilities were observed to influence the predictions. We also highlight how predictions are impacted by the underlying disease mechanisms of missense mutations and offer insights into understanding these to improve pathogenicity predictions. Our study presents aspects to take into consideration when adopting deep learning approaches for protein structure-guided pathogenicity predictions.
Differences of spinal cord gadolinium enhancement features of neuromyelitis optica spectrum disorder and long-segment degenerative cervical myelopathy
Authors: Sun Xingwen , Zhao Qiang , Zhang Lihua , Yuan Huishu
Published: July 2023

Objectives

Neuromyelitis optica spectrum disorder (NMOSD) and long-segment degenerative cervical myelopathy (DCM) may have a similar appearance on MRI. This study aimed to identify the differences in spinal cord gadolinium enhancement features between NMOSD and long-segment DCM.

Methods

Spinal cord gadolinium enhancement of 27 NMOSD patients and 30 long-segment DCM patients were retrospectively analyzed. Enhancements were evaluated for their number, length, location on the sagittal images, distribution on the axial images, and form on the sagittal images. The Wilcoxon rank sum test was performed to compare numerical variables. The Pearson chi-squared test was performed to compare categorical variables.

Results

The median number of enhanced lesions (p < 0.05), the median length of the enhancements (p < 0.05), and the location of enhancement on sagittal images (p < 0.05) of NMOSD patients and long-segment DCM patients showed significant differences. The axial distribution of enhancements did not show a significant difference between NMOSD and long-segment DCM patients (p = 0.115). On the sagittal images, linear and ring-formed enhancements were observed in 10 (27.0%) and 17 (63.0%) NMOSD patients, respectively. The enhancements in long-segment DCM patients had a transverse band or pancake-like appearance in 15 (50%) patients and an irregular flake-like appearance with a longitudinally oriented long axis in 15 patients (50%).

Conclusion

By analyzing the number, length, location, and form of the gadolinium enhancements, NMOSD and long-segment DCM could be well-differentiated.
High frequency of cerebrospinal fluid autoantibodies in patients with seizures or epilepsies of unknown etiology
Authors: Schulz Paulina , Lütt Alva , Stöcker Winfried , Teegen Bianca , Holtkamp Martin , Prüss Harald
Published: July 2023

Introduction

The increasing identification of specific autoantibodies against brain structures allows further refinement of the group of autoimmune-associated epilepsies and affects diagnostic and therapeutic algorithms. The early etiological allocation of a first seizure is particularly challenging, and the contribution of cerebrospinal fluid (CSF) analysis is not fully understood.

Methods

In this retrospective study with a mean of 7.8 years follow-up involving 39 well-characterized patients with the initial diagnosis of new-onset seizure or epilepsy of unknown etiology and 24 controls, we determined the frequency of autoantibodies to brain proteins in CSF/serum pairs using cell-based assays and unbiased immunofluorescence staining of unfixed murine brain sections.

Results

Autoantibodies were detected in the CSF of 30.8% of patients. Underlying antigens involved glial fibrillary acidic protein (GFAP) and N-methyl-D-aspartate (NMDA) receptors, but also a range of yet undetermined epitopes on neurons, glial and vascular cells. While antibody-positive patients had higher frequencies of cancer, they did not differ from antibody-negative patients with respect to seizure type, electroencephalography (EEG) and cranial magnetic resonance imaging (cMRI) findings, neuropsychiatric comorbidities or pre-existing autoimmune diseases. In 5.1% of patients with seizures or epilepsy of initially presumed unknown etiology, mostly CSF findings resulted in etiological reallocation as autoimmune-associated epilepy.

Discussion

These findings strengthen the potential role for routine CSF analysis. Further studies are needed to understand the autoantibody contribution to etiologically unclear epilepsies, including determining the antigenic targets of underlying autoantibodies.
Cortical activation during imagined walking for people with lower limb loss: a pilot study
Authors: Hunter Susan W. , Motala Aysha , Cronin Alicia E. , Bartha Robert , Viana Ricardo , Payne Michael W.
Published: July 2023

Each year in Canada, a substantial number of adults undergo limb amputation, with lower limb amputation (LLA) the most prevalent. Enhancing walking ability is crucial for optimizing rehabilitation outcomes, promoting participation, and facilitating community reintegration. Overcoming challenges during the acute post-amputation phase and sub-acute rehabilitation necessitates alternative approaches, such as motor imagery and mental practice, to maximize rehabilitation success. However, the current evidence on activation patterns using motor imagery in individuals with LLA is limited. The primary objective was to assess the feasibility of observing brain activation during imagined walking in individuals with LLA utilizing 3T functional magnetic resonance imaging (fMRI). Eight individuals with LLA and 11 control subjects participated. Consistent with representations of the lower limbs, both control and amputee groups demonstrated bilateral activation in the medial surface of the primary motor and somatosensory cortices. However, individuals with lower limb amputations exhibited significantly greater activation during imagined walking, particularly in frontal regions and the medial surface of the primary motor and supplementary motor cortices. Furthermore, the volume of activation in the bilateral primary motor cortices was higher for participants with amputations compared to controls. The protocol developed in this study establishes a foundation for evaluating the effects of a gait training program that incorporates mental imagery alongside conventional rehabilitation practices, in contrast to standard care alone. This pilot investigation holds potential to enhance our understanding of brain plasticity in individuals with LLA and pave the way for more effective rehabilitation strategies to optimize functional recovery and community reintegration.
Train duration and inter-train interval determine the direction and intensity of high-frequency rTMS after-effects
Authors: Jin Jingna , Wang Xin , Wang He , Li Ying , Liu Zhipeng , Yin Tao
Published: July 2023

Background and objective

It has been proved that repetitive transcranial magnetic stimulation (rTMS) triggers the modulation of homeostatic metaplasticity, which causes the effect of rTMS to disappear or even reverse, and a certain length of interval between rTMS trains might break the modulation of homeostatic metaplasticity. However, it remains unknown whether the effects of high-frequency rTMS can be modulated by homeostatic metaplasticity by lengthening the train duration and whether homeostatic metaplasticity can be broken by prolonging the inter-train interval.

Methods

In this study, 15 subjects participated in two experiments including different rTMS protocols targeting the motor cortex. In the first experiment, high-frequency rTMS protocols with different train durations (2 s and 5 s) and an inter-train interval of 25 s were adopted. In the second experiment, high-frequency rTMS protocols with a train duration of 5 s and different inter-train intervals (50 s and 100 s) were adopted. A sham protocol was also included. Changes of motor evoked potential amplitude acquired from electromyography, power spectral density, and intra-region and inter-region functional connectivity acquired from electroencephalography in the resting state before and after each rTMS protocol were evaluated.

Results

High-frequency rTMS with 2 s train duration and 25 s inter-train interval increased cortex excitability and the power spectral density of bilateral central regions in the alpha frequency band and enhanced the functional connectivity between central regions and other brain regions. When the train duration was prolonged to 5 s, the after-effects of high-frequency rTMS disappeared. The after-effects of rTMS with 5 s train duration and 100 s inter-train interval were the same as those of rTMS with 2 s train duration and 25 s inter-train interval.

Conclusion

Our results indicated that train duration and inter-train interval could induce the homeostatic metaplasticiy and determine the direction of intensity of rTMS after-effects, and should certainly be taken into account when performing rTMS in both research and clinical practice.
Risk factors for agitation in home-cared older adults with dementia: evidence from 640 elders in East China
Authors: Liu Jiaxin , Lin Taoyu , Liu Guanjun , Dong Xiaoxin , Min Rui
Published: July 2023

Background

Agitation is common among older adults with dementia, negatively affecting their quality of life and their caregivers’. Since home care remains the dominant approach for older adults, this study investigates the risk factors for agitation in older adults with dementia in China.

Methods

We perform a cross-sectional study of home-cared older adults with dementia in Ningbo, China, using 2020 data. We use a self-made questionnaire to investigate the risks of agitated behavior and its related factors. We perform descriptive, univariate, and regression analyses.

Findings

We address 640 older Chinese adults; 42.8% of the sample exhibits one or more agitated behaviors. We find that basic health issues, such as activities of daily living (ADL), family support issues, such as Zarit Burden Interview (ZBI) scale and Family APGAR Questionnaire (APGAR), and behavioral awareness issues, such as fall and scald, significantly influence the occurrence of agitation behaviors (p < 0.05). Older adults with severe ADL disorder (b = 6.835, β = 0.196, p < 0.001), ZBI score of 67.00–88.0 (b = 10.212, β = 0.248, p = 0.005), severe APGAR disorder (b = 3.699, β = 0.100, p = 0.012) and a history of fall (b = 9.311, β = 0.199, P = <0.001) or scald (b = 9.288, β = 0.125, p = 0.002) are more likely to exhibit agitated behaviors.

Interpretation

Agitated behavior in home-cared older adults with dementia are diverse and related to mental state, family support, and behavioral awareness issues. Caregivers, often family members, should be attentive to the needs of dementia patients and take active and effective measures to improve their quality of life. They should be aware of the causes and triggers of agitated behavior and take steps to reduce its occurrence.
CDC42—A promising immune-related target in glioma
Authors: Jiang Tao , Wang Xianwei , Huang Jiaming , Chen Dong
Published: July 2023

Glioma is the worst prognostic neoplasm in the central nervous system. A polarity-regulating GTPase in cells, known as cell division cycle 42 (CdC42), has been proven to have its overactivation tightly connected to high tumor malignancy. The RNA-seq and protein expression of CDC42 in tumor and comparison tissues were analyzed based on the online tools; CDC42 was remarkably boosted in tumor tissues compared to normal controls. A total of 600 patients in the analysis set from The Cancer Genome Atlas (TCGA) database and 657 patients in the validation set from the Chinese Glioma Genome Atlas (CGGA) database were adopted. The expression of CDC42 in clinical features and biological functions of glioma was analyzed, including differential expression analysis, survival analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune infiltration analysis. The enrichment of CDC42 was shown to be strongly associated with poor prognosis and terrible clinical indexes of glioma, including higher World Health Organization scale grade, wild-type isocitrate dehydrogenase 1 expression, O6-methylguanine-DNA methyltransferase non-methylated status, and 1p19q non-codeletion status (p < 0.0001). Functional enrichment analysis showed that CDC42 was highly correlated with immune and inflammatory responses in glioma. Additionally, the concentration extent of CDC42 was closely related to immune infiltration, immune checkpoints, and regulatory T (Treg) cell markers (CD4, CD25, and CD127). All evidence suggested that CDC42 may be a potential target for glioma immunotherapy.
Leptospermum extract (QV0) suppresses pleural mesothelioma tumor growth in vitro and in vivo by mitochondrial dysfunction associated apoptosis
Authors: Shi Huaikai , Zhang Le , Yu Ta-Kun , Zhuang Ling , Ke Helen , Johnson Ben , Rath Emma , Lee Kenneth , Klebe Sonja , Kao Steven , Qin Karl Lijun , Pham Hong Ngoc Thuy , Vuong Quan , Cheng Yuen Yee
Published: July 2023

Pleural mesothelioma (PM) is a highly aggressive, fast-growing asbestos-induced cancer with limited effective treatments. There has been interest in using naturally occurring anticancer agents derived from plant materials for the treatment of PM. However, it is unclear if an aqueous extract from Leptospermum polygalifolium (QV0) has activity against PM. Here we investigated the anti-cancer properties of QV0 and Defender® (QV0 dietary formula) in vitro and in vivo, respectively. QV0 suppressed the growth of eight PM cell lines in a dose-dependent manner, effective at concentrations as low as 0.02% w/v (equivalent to 0.2 mg/ml). This response was found to be associated with inhibited cell migration, proliferation, and colony formation but without evident cell cycle alteration. We observed mitochondrial dysfunction post-QV0 treatment, as evidenced by significantly decreased basal and maximal oxygen consumption rates. Ten SCID mice were treated with 0.25 mg/g Defender® daily and exhibited reduced tumor size over 30 days, which was associated with an average extension of seven days of mouse life. There was no evidence of liver toxicity or increased blood glucose post-treatment in animals treated with Defender®. Significantly enhanced tumor apoptosis was observed in the Defender®-treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender® were detected in HPLC analysis. To the best of our knowledge, this study constitutes the first demonstration of an improved host survival (without adverse effects) response in a QV0-treated PM mouse model, associated with evident inhibition of PM cell growth and mitochondrial dysfunction-related enhancement of tumor apoptosis.
Profiling of miRNAs and their interfering targets in peripheral blood mononuclear cells from patients with chronic myeloid leukaemia
Authors: Wu Sheng-Cheng , Lai Shiue-Wei , Lu Xin-Jie , Lai Hsing-Fan , Chen Yu-Guang , Chen Po-Huang , Ho Ching-Liang , Wu Yi-Ying , Chiu Yi-Lin
Published: July 2023

Introduction

MicroRNAs may be implicated in the acquisition of drug resistance in chronic myeloid leukemia as they regulate the expression of not only BCR-ABL1 but also genes associated with the activation of drug transfer proteins or essential signaling pathways.

Methods

To understand the impact of specifically expressed miRNAs in chronic myeloid leukemia and their target genes, we collected peripheral blood mononuclear cells (PBMC) from patients diagnosed with chronic myeloid leukemia (CML) and healthy donors to determine whole miRNA expression by small RNA sequencing and screened out 31 differentially expressed microRNAs (DE-miRNAs) with high expression. With the utilization of miRNA set enrichment analysis tools, we present here a comprehensive analysis of the relevance of DE-miRNAs to disease and biological function. Furthermore, the literature-based miRNA-target gene database was used to analyze the overall target genes of the DE-miRNAs and to define their associated biological responses. We further integrated DE-miRNA target genes to identify CML miRNA targeted gene signature singscore (CMTGSS) and used gene-set enrichment analysis (GSEA) to analyze the correlation between CMTGSS and Hallmark gene-sets in PBMC samples from clinical CML patients. Finally, the association of CMTGSS stratification with multiple CML cell lineage gene sets was validated in PBMC samples from CML patients using GSEA.

Results

Although individual miRNAs have been reported to have varying degrees of impact on CML, overall, our results show that abnormally upregulated miRNAs are associated with apoptosis and aberrantly downregulated miRNAs are associated with cell cycle. The clinical database shows that our defined DE-miRNAs are associated with the prognosis of CML patients. CMTGSS-based stratification analysis presented a tendency for miRNAs to affect cell differentiation in the blood microenvironment.

Conclusion

Collectively, this study defined differentially expressed miRNAs by miRNA sequencing from clinical samples and comprehensively analyzed the biological functions of the differential miRNAs in association with the target genes. The analysis of the enrichment of specific myeloid differentiated cells and immune cells also suggests the magnitude and potential targets of differentially expressed miRNAs in the clinical setting. It helps us to make links between the different results obtained from the multi-faceted studies to provide more potential research directions.
A five-collagen-based risk model in lung adenocarcinoma: prognostic significance and immune landscape
Authors: Dong Lingjun , Fu Linhai , Zhu Ting , Wu Yuanlin , Li Zhupeng , Ding Jianyi , Zhang Jiandong , Wang Xiang , Zhao Junjun , Yu Guangmao
Published: July 2023

As part of the tumor microenvironment (TME), collagen plays a significant role in cancer fibrosis formation. However, the collagen family expression profile and clinical features in lung adenocarcinoma (LUAD) are poorly understood. The objective of the present work was to investigate the expression pattern of genes from the collagen family in LUAD and to develop a predictive signature based on collagen family. The Cancer Genome Atlas (TCGA) samples were used as the training set, and five additional cohort samples obtained from the Gene Expression Omnibus (GEO) database were used as the validation set. A predictive model based on five collagen genes, including COL1A1, COL4A3, COL5A1, COL11A1, and COL22A1, was created by analyzing samples from the TCGA cohort using LASSO Cox analysis and univariate/multivariable Cox regression. Using Collagen-Risk scores, LUAD patients were then divided into high- and low-risk groups. KM survival analysis showed that collagen signature presented a robust prognostic power. GO and KEGG analyses confirmed that collagen signature was associated with extracellular matrix organization, ECM-receptor interaction, PI3K-Akts and AGE-RAGE signaling activation. High-risk patients exhibited a considerable activation of the p53 pathway and cell cycle, according to GSEA analysis. The Collage-Risk model showed unique features in immune cell infiltration and tumor-associated macrophage (TAM) polarization of the TME. Additionally, we deeply revealed the association of collagen signature with immune checkpoints (ICPs), tumor mutation burden (TMB), and tumor purity. We first constructed a reliable prognostic model based on TME principal component—collagen, which would enable clinicians to treat patients with LUAD more individually.
Copper metabolism and hepatocellular carcinoma: current insights
Authors: Zhou Cheng , Yang Jinqiu , Liu Tong , Jia Ran , Yang Lin , Sun Pengfei , Zhao Wenxia
Published: July 2023

Copper is an essential trace element that acts as a cofactor in various enzyme active sites in the human body. It participates in numerous life activities, including lipid metabolism, energy metabolism, and neurotransmitter synthesis. The proposal of “Cuproptosis” has made copper metabolism-related pathways a research hotspot in the field of tumor therapy, which has attracted great attention. This review discusses the biological processes of copper uptake, transport, and storage in human cells. It highlights the mechanisms by which copper metabolism affects hepatocellular carcinogenesis and metastasis, including autophagy, apoptosis, vascular invasion, cuproptosis, and ferroptosis. Additionally, it summarizes the current clinical applications of copper metabolism-related drugs in antitumor therapy.
Salivary glands adenoid cystic carcinoma: a molecular profile update and potential implications
Authors: da Silva Fernanda Jardim , Carvalho de Azevedo Juscelino , Ralph Ana Carolina Lima , Pinheiro João de Jesus Viana , Freitas Vanessa Morais , Calcagno Danielle Queiroz
Published: July 2023

Adenoid cystic carcinoma (ACC) is an aggressive tumor with a high propensity for distant metastasis and perineural invasion. This tumor is more commonly found in regions of the head and neck, mainly the salivary glands. In general, the primary treatment modality for ACC is surgical resection and, in some cases, postoperative radiotherapy. However, no effective systemic treatment is available for patients with advanced disease. Furthermore, this tumor type is characterized by recurrent molecular alterations, especially rearrangements involving the MYB, MYBL1, and NFIB genes. In addition, they also reported copy number alterations (CNAs) that impact genes. One of them is C-KIT, mutations that affect signaling pathways such as NOTCH, PI3KCA, and PTEN, as well as alterations in chromatin remodeling genes. The identification of new molecular targets enables the development of specific therapies. Despite ongoing investigations into immunotherapy, tyrosine kinase inhibitors, and anti-angiogenics, no systemic therapy is approved by the FDA for ACC. In this review, we report the genetic and cytogenetic findings on head and neck ACC, highlighting possible targets for therapeutic interventions.
Spinal cord stimulation for refractory pericarditis: a case report and a review of the mechanism of action
Authors: Elsliger Simon , Saucier Jacob , Schneider Andre , El Helou Antonios
Published: July 2023

Background and objectives

In recent years, spinal cord stimulation (SCS) has emerged as a promising management option for chronic pain of multiple etiologies. While its effectiveness has been strongly suggested in many patients, the exact mechanism of action of SCS is incompletely understood. This article reviews the leading mechanisms underlying the analgesic and cardiovascular effects of SCS and reports its novel benefits in a case of recurrent pericarditis.

Literature review

Throughout history, the analgesic properties of SCS were thought to arise via stimulation of the spinothalamic tract. Although this mechanism has been thoroughly reported, new research and patient outcomes from SCS have revealed various additional properties that cannot be fully explained by this mechanism alone. Evidence suggests that SCS enhances calcitonin gene-related peptide release and modulates inflammatory cytokine secretion, sympathetic tone, and inhibitory neurotransmitter secretion. These distinct mechanisms likely collectively contribute to the therapeutic effects of SCS on the cardiovascular system and pain management.

Case report

We report the case of a 48-year-old male patient with recurrent pericarditis, characterized by refractory angina-like pain and reduced left ventricular ejection fraction (LVEF). After 1 year of having a spinal cord stimulator implanted, the patient is free from pain and narcotics, with a reduction of 428 mg equivalent dose of morphine. The patient's LVEF increased from 40% to 45% without changes to his previous medical treatment. This is the first reported case of refractory pericarditis managed with spinal cord stimulation.

Conclusion

Recognizing the improved pain management, reduced narcotic usage, and improved LVEF in our patient following SCS is critical to paving the way toward a complete understanding of the mechanism of action of SCS. This case reveals the therapeutic potential of SCS for cardiovascular pathologies other than refractory angina pectoris.
Identification of five novel variants of ADAR1 in dyschromatosis symmetrica hereditaria by next-generation sequencing
Authors: Ma Qian , Che Lingyi , Chen Yibing , Gu Zhuoyu
Published: July 2023

Background

Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant inherited pigmentary dermatosis characterized by a mixture of hyperpigmented and hypopigmented freckles on the dorsal aspect of the distal extremities. To date, pathogenic mutations causing DSH have been identified in the adenosine deaminase acting on RNA1 gene (ADAR1), which is mapped to chromosome 1q21.

Objective

The present study aimed to investigate the underlying pathological mechanism in 14 patients with DSH from five unrelated Chinese families. Next-generation sequencing (NGS) and direct sequencing were performed on a proband with DSH to identify causative mutations. All coding, adjacent intronic, and 5′- and 3′-untranslated regions ofADAR1were screened, and variants were identified.

Result

These mutations consisted of three missense mutations (NM_001025107: c.716G>A, NM_001111.5: c.3384G>C, and NM_001111.5: c.3385T>G), one nonsense mutation (NM_001111.5:c.511G>T), and one splice-site mutation (NM_001111.5: c.2080-1G>T) located in exon 2, exon 14, and the adjacent intronic region according to recommended Human Genome Variation Society (HGVS) nomenclature. Moreover, using polymerase chain reaction and Sanger sequencing, we identified five novelADAR1variants, which can be predicted to be pathogenic by in silico genome sequence analysis. Among the mutations, the missense mutations had no significant effect on the spatial structure of the protein, while the stop codon introduced by the nonsense mutation truncated the protein.

Conclusion

Our results highlighted that the advent of NGS has facilitated high-throughput screening for the identification of disease-causing mutations with high accuracy, stability, and specificity. Five novel genetic mutations were found in five unrelated families, thereby extending the pathogenic mutational spectrum ofADAR1in DSH and providing new insights into this complex genetic disorder.
Emerging roles of microRNAs in septic cardiomyopathy
Authors: Wu Mingyan , Li Guangdong , Wang Wenjun , Ren Hongsheng
Published: July 2023

As one of the serious complications of sepsis, septic cardiomyopathy has gained more and more attention, because of its high morbidity and mortality. With the in-depth study of septic cardiomyopathy, several methods have been adopted clinically but have poor therapeutic effects due to failure to find precise therapeutic targets. In recent years, microRNAs have been found to be related to the pathogenesis, diagnosis, and treatment of septic cardiomyopathy via regulating immunity and programmed cell death. This paper reviews the role of microRNAs in septic cardiomyopathy, aiming to provide new targets for the diagnosis and treatment of septic cardiomyopathy.
Comparative transcriptomics reveals the role of altered energy metabolism in the establishment of single-cell C4 photosynthesis in Bienertia sinuspersici
Authors: Han Sang-Yun , Kim Woe-Yeon , Kim Jung Sun , Hwang Inhwan
Published: July 2023

Single-cell C4 photosynthesis (SCC4) in terrestrial plants without Kranz anatomy involves three steps: initial CO2 fixation in the cytosol, CO2 release in mitochondria, and a second CO2 fixation in central chloroplasts. Here, we investigated how the large number of mechanisms underlying these processes, which occur in three different compartments, are orchestrated in a coordinated manner to establish the C4 pathway in Bienertia sinuspersici, a SCC4 plant. Leaves were subjected to transcriptome analysis at three different developmental stages. Functional enrichment analysis revealed that SCC4 cycle genes are coexpressed with genes regulating cyclic electron flow and amino/organic acid metabolism, two key processes required for the production of energy molecules in C3 plants. Comparative gene expression profiling of B. sinuspersici and three other species (Suaeda aralocaspica, Amaranthus hypochondriacus, and Arabidopsis thaliana) showed that the direction of metabolic flux was determined via an alteration in energy supply in peripheral chloroplasts and mitochondria via regulation of gene expression in the direction of the C4 cycle. Based on these results, we propose that the redox homeostasis of energy molecules via energy metabolism regulation is key to the establishment of the SCC4 pathway in B. sinuspersici.
Hsf transcription factor gene family in peanut (Arachis hypogaea L.): genome-wide characterization and expression analysis under drought and salt stresses
Authors: Wang Qi , Zhang Zhenbiao , Guo Cun , Zhao Xiaobo , Li Zhiyuan , Mou Yifei , Sun Quanxi , Wang Juan , Yuan Cuiling , Li Chunjuan , Cong Ping , Shan Shihua
Published: July 2023

Heat shock transcription factors (Hsfs) play important roles in plant developmental regulations and various stress responses. In present study, 46 Hsf genes in peanut (AhHsf) were identified and analyzed. The 46 AhHsf genes were classed into three groups (A, B, and C) and 14 subgroups (A1-A9, B1-B4, and C1) together with their Arabidopsis homologs according to phylogenetic analyses, and 46 AhHsf genes unequally located on 17 chromosomes. Gene structure and protein motif analysis revealed that members from the same subgroup possessed similar exon/intron and motif organization, further supporting the results of phylogenetic analyses. Gene duplication events were found in peanut Hsf gene family via syntenic analysis, which were important in Hsf gene family expansion in peanut. The expression of AhHsf genes were detected in different tissues using published data, implying that AhHsf genes may differ in function. In addition, several AhHsf genes (AhHsf5, AhHsf11, AhHsf20, AhHsf24, AhHsf30, AhHsf35) were induced by drought and salt stresses. Furthermore, the stress-induced member AhHsf20 was found to be located in nucleus. Notably, overexpression of AhHsf20 was able to enhance salt tolerance. These results from this study may provide valuable information for further functional analysis of peanut Hsf genes.
The relationship between sleep disturbance and obsessive– compulsive symptoms: the mediation of repetitive negative thinking and the moderation of experiential avoidance
Authors: Zhao Xudong , Shen Liao , Pei Yufei , Wu Xiaojun , Zhou Ningning
Published: July 2023

Background

Studies have found that sleep disturbance is associated with obsessive–compulsive symptoms. This study aimed to elaborate on the mediating and moderating mechanisms between these two variables. We hypothesized that repetitive negative thinking plays a mediating role in the relationship between sleep disturbance and obsessive–compulsive symptoms, and experiential avoidance plays a moderating role.

Method

This study included 639 Chinese adults. A questionnaire survey was used to assess sleep quality, obsessive–compulsive symptoms, experiential avoidance, repetitive negative thinking, and depression symptoms. A moderated mediation model was established.

Results

After controlling for depressive symptoms, repetitive negative thinking partially mediated the positive correlation between sleep disturbance and obsessive–compulsive symptoms. This indirect relationship was significant in individuals with lower experiential avoidance levels. Particularly, the relationship between sleep disturbance and repetitive negative thinking was significant among individuals with lower experiential avoidance levels, but not among individuals with higher experiential avoidance levels.

Conclusion

This study demonstrated that repetitive negative thinking partially mediated the impact of sleep disturbance on obsessive–compulsive symptoms. The findings suggest that when providing support to individuals with sleep disturbance and obsessive–compulsive symptoms, assessing their level of experiential avoidance is necessary for performing targeted interventions. Individuals with low experiential avoidance may benefit from a clinical intervention targeting repetitive negative thinking to improve sleep quality and obsessive–compulsive symptoms.