bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance experiment of ultra high temperature cementing slurry system
Authors: Zou Qiang , Chen Xu , Zhong Shiming , Yi Dan , Liu Liankai
Published: April 2024

Introduction: The escalating pursuit of oil and gas reserves in China has led to increasingly deep and ultra-deep well drilling, encountering extreme temperatures that challenge the heat resistance capabilities of cement slurries. This study addresses the critical need for high-performance cement slurries capable of withstanding ultra-high temperatures during drilling and completion operations.

Methods: A novel ultrahigh temperature conventional density (UHTE) cement slurry was formulated by incorporating high-temperature-resistant additives, namely DRF-1S and DRH-2L. An indoor testing framework was established to assess the slurry’s performance across various parameters: Evaluating the slurry’s ability to maintain uniform consistency over time. Measuring the amount of free water separated from the slurry under simulated downhole conditions. Assessing the slurry’s transition from fluid to solid state over time. Determining the compressive strength and other mechanical attributes after curing at elevated temperatures.

Results: The experimental findings revealed the following: An optimal silica sand dosage of 50% was found to enhance the overall performance of the UHTE cement slurry. The developed UHTE cement system, fortified with DRF-1S and DRH-2L, demonstrated effective functionality within a temperature range of 180°C to 210°C, representing a significant advancement in high-temperature resistance. The slurry maintained API water loss below 100 mL, ensuring minimal fluid loss during placement. Adjusted thickening time allowed for adequate pumping and placement without premature setting. Settlement stability was maintained below 0.04 g/cm3, indicating excellent homogeneity and stability. Incorporation of the anti-decay material DRB-3S ensured a 28-day compressive strength exceeding 50 MPa at 210°C, signifying robust structural integrity under extreme thermal conditions.

Discussion: This research provides a robust foundation for the practical application of UHTE cementing technology in ultra-high temperature environments. The successful development of the UHTE cement slurry system, characterized by its superior temperature resistance, controlled water loss, optimized thickening behavior, and exceptional mechanical properties, paves the way for field trials and further enhancements. Future work will involve testing the effectiveness of the new additive combination under actual downhole conditions and refining the formulation to develop an even more advanced UHTE cementing additive. These advancements will contribute to enhanced wellbore integrity, improved drilling efficiency, and increased safety in deep and ultra-deep oil and gas exploration endeavors in China.
Periodic limb movements in patients with suspected obstructive sleep apnea without comorbid conditions
Authors: Seifen Christopher , Herrmann Moritz , Pordzik Johannes , Matthias Christoph , Gouveris Haralampos
Published: April 2024

Background

Periodic limb movement disorder (PLMD) and obstructive sleep apnea (OSA) are overlapping clinical syndromes with common risk factors. However, current literature has failed to establish a clear pathophysiological link between them. Thus, little is known about periodic limb movements (PLM) in otherwise healthy patients with suspected OSA.

Methods

We performed a retrospective analysis of 112 patients (age: 44.5 ± 12.0 years, 14.3% female) with suspected OSA who underwent full night polysomnography for the first time. Patients with chronic diseases of any kind, recent infections, malignancies, or daily or regular use of any type of medication were excluded. Group comparisons were made based on the severity of OSA (using the apnea hypopnea index, AHI) or the periodic limb movement index (PLMI).

Results

Both, PLMI and the total number of periodic limb movements during sleep (PLMS), showed a significant increase in patients with severe OSA. In addition, AHI and apnea index (AI) were significantly higher in patients with PLMI >15/h, with a similar trend for hypopnea index (HI) (p < 0.001, p < 0.001, and p > 0.05, respectively). PLMI was significantly positive correlated with AHI, AI, and HI (r = 0.392, p < 0.001; r = 0.361, p < 0.001; and r = 0.212, p < 0.05, respectively). Patients with PLMI >15/h were significantly older (p < 0.001). There was no significant association between body mass index (BMI) and PLMI >15/h.

Conclusion

We found a significant association between the severity of OSA and PLM in our study population with suspected OSA but without other comorbidities. PLMI and PLMS were significantly increased in patients with severe OSA. Future prospective studies with larger collectives should verify the presented results and should include mechanistic aspects in their evaluation.
SpoIVA is an essential morphogenetic protein for the formation of heat- and lysozyme-resistant spores in Clostridium sporogenes NBRC 14293
Authors: Kuwana Ritsuko , Dupuy Bruno , Martin-Verstraete Isabelle , Takamatsu Hiromu
Published: April 2024

Clostridium sporogenes is an anaerobic spore-forming bacterium genetically related to Clostridium botulinum but lacks toxin genes. The sporulation mechanism and spore structures of anaerobic bacteria, including C. sporogenes, have not been comprehensively analyzed. Based on 16S rRNA gene analysis, it has been determined that C. sporogenes NBRC 14293 belongs to C. botulinum Group I. Moreover, SpoIVA is highly conserved in Bacillus and Clostridium species. Therefore, the aim of the present study is to investigate the mechanism of spore formation in C. sporogenes by performing a functional analysis of spoIVA encoding SpoIVA, a protein involved in the early development of the spore coat and cortex in Bacillus subtilis. Inactivation of spoIVA in C. sporogenes resulted in the loss of resistance of sporulating cells to lysozyme and heat treatments. Phase-contrast microscopy indicated that the inactivation of spoIVA caused the development of abnormal forespores and production of only a few immature spores. In the spoIVA mutant, abnormal swirl structures were detected in the mother cell using both phase-contrast and transmission electron microscopy. These swirls were stained with auramine O, pararosaniline hydrochloride, and 2-(4-aminophenyl)benzothiazole to examine the surface of mature spores of the wild-type strain. We found that the spore coat and exosporium proteins were misassembled and that they accumulated in the mother cells of the mutant. The results of this study indicate that SpoIVA is a spore morphogenetic protein, providing novel insights into spore morphogenesis in C. sporogenes.
The characteristics of intratumoral microbial community reflect the development of lung adenocarcinoma
Authors: Su Yanfang , Li Shiyu , Sang Die , Zhang Yurong
Published: April 2024

Introduction

An increasing number of studies have demonstrated the pivotal role of microbiota changes in the onset, progression, diagnosis, treatment, and prognosis of lung adenocarcinoma (LUAD). However, a comprehensive analysis of intratumoral microbiome variation across distinct LUAD stages has not been performed. The aim of this study was to identify the microbial markers that significantly vary during tumor stage of LUAD.

Methods

Here, we used the cancer genome atlas (TCGA) database to comprehensively compare and analyze the differences in microbial composition between 267 patients with early and 224 patients with advanced LUAD. In order to determine the best biomarkers, we used the random forest (RF) model and found that the microbial markers have a certain ability in predicting the stage of LUAD.

Results

We found that there were certain differences in the microbiome of patients with LUAD at different stages, especially in the tumor tissues of patients with advanced LUAD, whose co-abundance network was significantly more complex. We also found that five bacterial biomarkers (Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, Loktanella, and Serratia) were correlated with LUAD stage, among which Pseudoalteromonas, Luteibacter, Caldicellulosiruptor, and Serratia were significantly overexpressed in patients with advanced LUAD. In particular, after integrating the biomarkers of mRNA, we achieved an area under the curve (AUC) of 0.70.

Discussion

Our study revealed the microbial profile of patients with LUAD and the intrinsic pathogenic mechanism between the microbiome and the disease, and established a multi-omics model to determine LUAD tumor stage.
Unraveling the dynamic transcriptomic changes during the dimorphic transition of Talaromyces marneffei through time-course analysis
Authors: Du Minghao , Tao Changyu , Hu Xueyan , Zhang Yun , Kan Jun , Wang Juan , Yang Ence
Published: April 2024

Introduction

Systemic dimorphic fungi pose a significant public health challenge, causing over one million new infections annually. The dimorphic transition between saprophytic mycelia and pathogenic yeasts is strongly associated with the pathogenesis of dimorphic fungi. However, despite the dynamic nature of dimorphic transition, the current omics studies focused on dimorphic transition primarily employ static strategies, partly due to the lack of suitable dynamic analytical methods.

Methods

We conducted time-course transcriptional profiling during the dimorphic transition of Talaromyces marneffei, a model organism for thermally dimorphic fungi. To capture non-uniform and nonlinear transcriptional changes, we developed DyGAM-NS (dynamic optimized generalized additive model with natural cubic smoothing). The performance of DyGAM-NS was evaluated by comparison with seven other commonly used time-course analysis methods. Based on dimorphic transition induced genes (DTIGs) identified by DyGAM-NS, cluster analysis was utilized to discern distinct gene expression patterns throughout dimorphic transitions of T. marneffei. Simultaneously, a gene expression regulatory network was constructed to probe pivotal regulatory elements governing the dimorphic transitions.

Results

By using DyGAM-NS, model, we identified 5,223 DTIGs of T. marneffei. Notably, the DyGAM-NS model showcases performance on par with or superior to other commonly used models, achieving the highest F1 score in our assessment. Moreover, the DyGAM-NS model also demonstrates potential in predicting gene expression levels throughout temporal processes. The cluster analysis of DTIGs suggests divergent gene expression patterns between mycelium-to-yeast and yeast-to-mycelium transitions, indicating the asymmetrical nature of two transition directions. Additionally, leveraging the identified DTIGs, we constructed a regulatory network for the dimorphic transition and identified two zinc finger-containing transcription factors that potentially regulate dimorphic transition in T. marneffei.

Discussion

Our study elucidates the dynamic transcriptional profile changes during the dimorphic transition of T. marneffei. Furthermore, it offers a novel perspective for unraveling the underlying mechanisms of fungal dimorphism, emphasizing the importance of dynamic analytical methods in understanding complex biological processes.
Characterization and potential lipid-lowering effects of lactic acid bacteria isolated from cats
Authors: Liang Shukun , Kang Yanhua , Zhao Ya , Sun Jintao , Wang Xiumin , Tao Hui , Wang Zhenlong , Wang Jinquan , Zhong Yougang , Han Bing
Published: April 2024

Introduction

This study aimed to study the characterization and the potential lipid-lowering effects of new isolated lactic acid bacteria from the feces of healthy adult cats.

Methods

We collected 85 cat fecal samples, isolated, screening lactic acid bacteria strains from samples, and investigated their in vitro and in vivo biological properties.

Results

A total of 221 lactic acid bacteria strains were isolated from 85 cat fecal samples. Sixteen strains with calcium dissolution rings greater than 1 mm were identified and selected for further characterization. Three lactic acid bacteria strains, Lactobacillus plantarum L-27-2, Pediococcus lactis L-14-1, and Enterococcus faecium, were identified as showing the most promising rates of cholesterol degradation (greater than 20%) and bacteriostatic radius (over 15 mm). These three strains exhibited robust growth and adherence to epithelial cells, along with adaptability to low pH (greater than 70%) and high bile salt conditions (greater than 60%), and remarkable cholesterol degradation and anti-pathogen activity. Sixteen mice were fed a high-fat diet (HFD) from 4 to 8 weeks of age, while a control group of the same size received a normal diet (ND). At 8 weeks of age, serum, feces and adipose tissue were collected. The results showed that, compared with mice fed an HFD diet alone, all mice fed an HFD diet plus lactic acid bacteria could decrease weight gain. P < 0.05 and the pathological changes of adipose tissue were alleviated. In addition, mice fed L-14-1 and F203 showed abdominal fat accumulation decreased (P < 0.05). Mice fed L-27-2 showed serum and liver triglyceride (TG) decreased (P < 0.05) and mice fed F203 showed serum high density lipoprotein cholesterol (HDL-C) increased (P < 0.01). mice fed L-27-2 and L-14-1 showed inflammatory cytokines (IL-6) was decreased (P < 0.01) Analysis of the fecal microbiota of mice fed these three lactic acid bacteria strains revealed alterations in the gut microbial community. There were common changes in intestinal microbes in mice fed these three lactic acid bacteria: (1) Bacteroides decreased; (2) Myxococcus increased; (3) Lachnoclostridium decreased. The microbes mentioned are all part of the core intestinal flora.

Discussion

This study provided three potential lactic acid bacteria for alleviating animal obesity and inflammation.
Integrated transcriptome and metabolome profiling reveals mechanisms underlying the infection of Cytospora mali in “Jin Hong” branches
Authors: Zhao Jing , Guo Yuan , Li Zhengnan , Shi Yajun , Sun Pingping
Published: April 2024

Introduction

Valsa canker, caused by Cytospora mali, is a destructive disease in apple production. However, the mechanism by which apple defend against C. mali infection remains unclear.

Methods

In this study, the integrative transcriptional and metabolic analysis were used to investigate the responses of the ‘Jin Hong’ apple branches to the invasion of C. mali.

Results and Discussion

Results showed that the differentially expressed genes were mainly enriched in the pathways of carbon metabolism, photosynthesis-antenna proteins, and biosynthesis of amino acids pathways. Additionally, the differentially accumulated metabolites were significantly enriched in aminoacyl-tRNA biosynthesis, fructose and mannose metabolism, and alanine, aspartate, and glutamate metabolism pathways. Conjoint analysis revealed that C. mali infection significantly altered 5 metabolic pathways, 8 highly relevant metabolites and 15 genes of apples. Among which the transcription factors WRKY and basic domain leucine zipper transcription family were induced, the α-linolenic acid and betaine were significantly accumulated in C. mali infected apple stems. This work presents an overview of the changes in gene expression and metabolic profiles in apple under the inoculation of C. mali, which may help to further screen out the mechanism of plant-pathogen interaction at the molecular level.
Exploration of the causal associations between circulating inflammatory proteins, immune cells, and neuromyelitis optica spectrum disorder: a bidirectional Mendelian randomization study and mediation analysis
Authors: Chen Zhiqing , Guo Yujin , Sun Huaiyu , Zhang Wuqiong , Hou Shuai , Guo Yu , Ma Xiaohui , Meng Hongmei
Published: April 2024

Background

An increasing body of research has demonstrated a robust correlation between circulating inflammatory proteins and neuromyelitis optica spectrum disorders (NMOSD). However, whether this association is causal or whether immune cells act as mediators currently remains unclear.

Methods

We employed bidirectional two-sample Mendelian randomization (TSMR) analysis to examine the potential causal association between circulating inflammatory proteins, immune cells, and NMOSD using data from genome-wide association studies (GWAS). Five different methods for Mendelian randomization analyses were applied, with the inverse variance-weighted (IVW) method being the primary approach. Sensitivity analyses were further performed to assess the presence of horizontal pleiotropy and heterogeneity in the results. Finally, a two-step Mendelian randomization (MR) design was employed to examine the potential mediating effects of immune cells.

Results

A notable causal relationship was observed between three circulating inflammatory proteins (CSF-1, IL-24, and TNFRSF9) and genetically predicted NMOSD. Furthermore, two immune cell phenotypes, genetically predicted CD8 on naive CD8+ T cells, and Hematopoietic Stem Cell Absolute Count were negatively and positively associated with genetically predicted NMOSD, respectively, although they did not appear to function as mediators.

Conclusion

Circulating inflammatory proteins and immune cells are causally associated with NMOSD. Immune cells do not appear to mediate the pathway linking circulating inflammatory proteins to NMOSD.
Magnetic resonance-guided focused ultrasound unilateral thalamotomy for medically refractory essential tremor: 3-year follow-up data
Authors: Tamburin Stefano , Paio Fabio , Bovi Tommaso , Bulgarelli Giorgia , Longhi Michele , Foroni Roberto , Mantovani Elisa , Polloniato Paolo Maria , Tagliamonte Micaela , Zivelonghi Emanuele , Zucchella Chiara , Cavedon Carlo , Nicolato Antonio , Petralia Benedetto , Sala Francesco , Bonetti Bruno , Tinazzi Michele , Montemezzi Stefania , Ricciardi Giuseppe Kenneth
Published: April 2024

Introduction

Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy of the ventralis intermediate (Vim) nucleus is an “incisionless” treatment for medically refractory essential tremor (ET). We present data on 49 consecutive cases of MRgFUS Vim thalamotomy followed-up for 3 years and review the literature on studies with longer follow-up data.

Methods

A retrospective chart review of patients who underwent MRgFUS thalamotomy (January 2018–December 2020) at our institution was performed. Clinical Rating Scale for Tremor (CRST) and Quality of Life in Essential Tremor (QUEST) scores were obtained pre-operatively and at each follow-up with an assessment of side effects. Patients had post-operative magnetic resonance imaging within 24 h and at 1 month to figure out lesion location, size, and extent. The results of studies with follow-up ≥3 years were summarized through a literature review.

Results

The CRST total (baseline: 58.6 ± 17.1, 3-year: 40.8 ± 18.0) and subscale scores (A + B, baseline: 23.5 ± 6.3, 3-year: 12.8 ± 7.9; C, baseline: 12.7 ± 4.3, 3-year: 5.8 ± 3.9) and the QUEST score (baseline: 38.0 ± 14.8, 3-year: 18.7 ± 13.3) showed significant improvement that was stable during the 3-year follow-up. Three patients reported tremor recurrence and two were satisfactorily retreated. Side effects were reported by 44% of patients (severe: 4%, mild and transient: 40%). The improvement in tremor and quality of life in our cohort was consistent with the literature.

Conclusion

We confirmed the effectiveness and safety of MRgFUS Vim thalamotomy in medically refractory ET up to 3 years.
Patients with chronic ankle instability exhibit increased sensorimotor cortex activation and correlation with poorer lateral balance control ability during single-leg stance: a FNIRS study
Authors: Liu Na , Yang Chen , Song Qipeng , Yang Fengying , Chen Yan
Published: April 2024

Introduction

Chronic Ankle Instability (CAI) is a musculoskeletal condition that evolves from acute ankle sprains, and its underlying mechanisms have yet to reach a consensus. Mounting evidence suggests that neuroplastic changes in the brain following ankle injuries play a pivotal role in the development of CAI. Balance deficits are a significant risk factor associated with CAI, yet there is a scarcity of evidence regarding the sensorimotor cortical plasticity related to balance control in affected individuals. This study aims to evaluate the differences in cortical activity and balance abilities between patients with CAI and uninjured individuals during a single-leg stance, as well as the correlation between these factors, in order to elucidate the neurophysiological alterations in balance control among patients with CAI.

Methods

The study enrolled 24 patients with CAI and 24 uninjured participants. During single-leg stance, cortical activity was measured using a functional near-infrared spectroscopy (fNIRS) system, which included assessments of the pre-motor cortex (PMC), supplementary motor area (SMA), primary motor cortex (M1), and primary somatosensory cortex (S1). Concurrently, balance parameters were tested utilizing a three-dimensional force platform.

Results

Independent sample t-tests revealed that, compared with the uninjured individuals, the patients with CAI exhibited a significant increase in the changes of oxyhemoglobin concentration (ΔHbO) during single-leg stance within the left S1 at Channel 5 (t = 2.101, p = 0.041, Cohen’s d = 0.607), left M1 at Channel 6 (t = 2.363, p = 0.022, Cohen’s d = 0.682), right M1 at Channel 15 (t = 2.273, p = 0.029, Cohen’s d = 0.656), and right PMC/SMA at Channel 11 (t = 2.467, p = 0.018, Cohen’s d = 0.712). Additionally, the center of pressure root mean square (COP-RMS) in the mediolateral (ML) direction was significantly greater (t = 2.630, p = 0.012, Cohen’s d = 0.759) in the patients with CAI. Furthermore, a moderate positive correlation was found between ML direction COP-RMS and ΔHbO2 in the M1 (r = 0.436; p = 0.033) and PMC/SMA (r = 0.488, p = 0.016), as well as between anteroposterior (AP) direction COP-RMS and ΔHbO in the M1 (r = 0.483, p = 0.017).

Conclusion

Patients with CAI demonstrate increased cortical activation in the bilateral M1, ipsilateral PMC/SMA, and contralateral S1. This suggests that patients with CAI may require additional brain resources to maintain balance during single-leg stance, representing a compensatory mechanism to uphold task performance amidst diminished lateral balance ability in the ankle joint.
EBV and multiple sclerosis: expression of LMP2A in MS patients
Authors: Agostini Simone , Mancuso Roberta , Caputo Domenico , Rovaris Marco , Clerici Mario
Published: April 2024

Several evidences, including increased serum titers of Epstein–Barr virus (EBV)-specific antibodies and the presence of EBV DNA in brain of patients suggest a possible role of this virus in the pathogenesis of Multiple Sclerosis (MS), a chronic neurodegenerative disease with an unknown etiopathology. Aim of the present study is to verify if the expression of LMP2A and EBNA-1, two EBV genes, is altered in MS patients. EBV viral load, LMP2A and EBNA-1 gene expression and EBNA-1 antibodies titers were evaluated in blood of EBV-seropositive MS patients (n = 57; 31 relapsing remitting –RRMS- and 26 progressive -PMS-patients) and age- and sex-matched healthy controls (HC, n = 49). Results showed that EBNA-1 and VCA antibodies titers are significantly augmented in MS patients compared to HC (p < 0.05 for both antibodies); detection of EBV DNA was more frequent as well in MS patients compared to HC, although without reaching statistical significance. Regarding viral gene expression, LMP2A was significantly more frequently detected and more expressed in MS patients compared to HC (p < 0.005) whereas no differences were observed for EBNA-1. Considering patients alone, EBNA-1 was significantly more frequent in PMS compared to RRMS (p < 0.05), whereas no differences were observed for LMP2A. Increased expression of the LMP2A latency-associated gene in MS patients supports the hypothesis that EBV plays a role in disease etiopathology.
Advances in aqueous humor proteomics for biomarker discovery and disease mechanisms exploration: a spotlight on primary open angle glaucoma
Authors: Beutgen Vanessa M. , Graumann Johannes
Published: April 2024

Altered protein levels in the aqueous humor (AH) may be a valuable source of novel biomarkers in neurodegenerative retinal disease. The proximity of this body fluid to the disease focus, and its corresponding enrichment for tissue specific proteins, renders it an excellent matrix to study underlying molecular mechanisms. Novel proteomic methods accordingly hold large potential for insight into pathologies based on the composition of the AH proteome, including primary open angle glaucoma (POAG). Recent mass spectrometry-based studies use novel approaches to tackle the challenges arising from the combination of low available sample volume and protein concentration, thereby increasing proteome coverage. But despite significant improvements in mass spectrometry (MS), a different class of proteomic technologies is poised to majorly impact the analysis of ocular biofluids. Affinity proteomic workflows, having become available commercially recently, have started to complement data obtained by MS and likely will grow into a crucial tool for ophthalmological biomarker research. This review highlights corresponding approaches in proteome analysis of aqueous humor and discusses recent findings on alterations of the AH proteome in POAG.
Efficiency of moderately hypofractionated radiotherapy in NSCLC cell model
Authors: Lüdeking Marcus , Stemwedel Katharina , Ramachandran Dhanya , Grosche Sinja , Christiansen Hans , Merten Roland , Henkenberens Christoph , Bogdanova Natalia V.
Published: April 2024

Background

The current standard of radiotherapy for inoperable locally advanced NSCLCs with single fraction doses of 2.0 Gy, results in poor outcomes. Several fractionation schedules have been explored that developed over the past decades to increasingly more hypofractionated treatments. Moderate hypofractionated radiotherapy, as an alternative treatment, has gained clinical importance due to shorter duration and higher patient convenience. However, clinical trials show controversial results, adding to the need for pre-clinical radiobiological studies of this schedule.

Methods

We examined in comparative analysis the efficiency of moderate hypofractionation and normofractionation in four different NSCLC cell lines and fibroblasts using several molecular-biological approaches. Cells were daily irradiated with 24x2.75 Gy (moderate hypofractionation) or with 30x2 Gy (normofractionation), imitating the clinical situation. Proliferation and growth rate via direct counting of cell numbers, MTT assay and measurements of DNA-synthesizing cells (EdU assay), DNA repair efficiency via immunocytochemical staining of residual γH2AX/53BP1 foci and cell surviving via clonogenic assay (CSA) were experimentally evaluated.

Results

Overall, the four tumor cell lines and fibroblasts showed different sensitivity to both radiation regimes, indicating cell specificity of the effect. The absolute cell numbers and the CSA revealed significant differences between schedules (P < 0.0001 for all employed cell lines and both assays) with a stronger effect of moderate hypofractionation.

Conclusion

Our results provide evidence for the similar effectiveness and toxicity of both regimes, with some favorable evidence towards a moderate hypofractionation. This indicates that increasing the dose per fraction may improve patient survival and therapy outcomes.
Drug-eluting beads transcatheter arterial chemoembolization combined with systemic therapy versus systemic therapy alone as first-line treatment for unresectable colorectal liver metastases
Authors: Wang Fuquan , Chen Lei , Bin Chai , Cao Yanyan , Wang Jihua , Zhou Guofeng , Zheng Chuansheng
Published: April 2024

Purpose

The purpose of this retrospective study was to compare the therapeutic efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with systemic therapy to systemic therapy alone as first-line treatment for unresectable patients with colorectal liver metastases (CRLM).

Methods

From December 2017 to December 2022, patients with unresectable CRLM who received systemic therapy with or without DEB-TACE as first-line treatment were included in the study. The primary endpoint was progression-free survival (PFS). Secondary endpoints were tumor response, conversion rate and adverse events.

Results

Ninety-eight patients were enrolled in this study, including 46 patients who received systemic therapy combined with DEB-TACE (DEB-TACE group) and 52 patients who received systemic therapy alone (control group). The median PFS was elevated in the DEB-TACE group compared with the control group (12.1 months vs 8.4 months, p = 0.008). The disease control rate was increased in the DEB-TACE group compared with the control group (87.0% vs 67.3%, p = 0.022). Overall response rates (39.1% vs 25.0%; p = 0.133) and conversion rate to liver resection (33.8% vs 25.0%; p = 0.290) were no different between the two groups. The multivariate analysis showed that treatment options, size of liver metastasis, number of liver metastasis, synchronous metastases, and extrahepatic metastases were independent prognostic factor of PFS. Further subgroup analyses illustrated that PFS was beneficial with the DEB-TACE group in patients with age ≥ 60, male, left colon, synchronous metastases, bilobar, number of liver metastasis > 5, extrahepatic metastases, non-extrahepatic metastases, CEA level < 5 (ng/ml), and KRAS wild-type. No grade 4 or 5 toxicities related to DEB-TACE procedures were observed.

Conclusion

In patients with unresectable CRLM, systemic chemotherapy with DEB-TACE as first-line treatment may improve progression-free survival and disease control rate outcomes over systemic chemotherapy alone with manageable safety profile.
Plasma IGFBP-3 and IGFBP-5 levels are decreased during acute manic episodes in bipolar disorder patients
Authors: Fernández-Pereira Carlos , Penedo Maria Aránzazu , Alonso-Núñez Adrián , Rivera-Baltanás Tania , Viéitez Irene , Prieto-González José María , Vilariño-Vilariño María Isabel , Olivares José Manuel , Ortolano Saida , Agís-Balboa Roberto Carlos
Published: April 2024

Introduction: Bipolar disorder (BD) is a recurrent and disabling psychiatric disorder related to low-grade peripheral inflammation and altered levels of the members of the insulin-like growth factor (IGF) family. The aim of this study was to evaluate the plasma levels of IGF-2, insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, IGFBP-5, IGFBP-7, and inflammatory markers such as tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1β (MIP-1β).

Methods: We used the Young Mania Rating Scale (YMRS) to determine the severity of the symptomatology, while proteins were measured by enzyme-linked immunosorbent assay (ELISA). We included 20 patients with BD who suffered a manic episode and 20 controls. Some BD patients (n = 10) were evaluated after a period (17 ± 8 days) of pharmacological treatment.

Results: No statistical difference was found in IGF-2, IGFBP-1, IGFBP-7, TNF-α, and MIP-1β levels. However, IGFBP-3 and IGFBP-5 levels were found to be statistically decreased in BD patients. Conversely, the MCP-1 level was significantly increased in BD patients, but their levels were normalized after treatment. Intriguingly, only IGFBP-1 levels were significantly decreased after treatment. No significant correlation was found between the YMRS and any of the proteins studied either before or after treatment or between IGF proteins and inflammatory markers.

Discussion: To some extent, IGFBP-3 and IGFBP-5 might be further explored as potential indicators of treatment responsiveness or diagnosis biomarkers in BD.
Establishment of a prognostic risk model for osteosarcoma and mechanistic investigation
Authors: Jiang Hongyuan , Zhao Xuliang , Zang Jinhui , Wang Ruijiao , Gao Jiake , Chen Jinli , Yu Tengbo
Published: April 2024

Objective: To investigate the immune mechanism of osteosarcoma (OS)-specific markers to mitigate bone destruction in the aggressive OS, prone to recurrence and metastasis.

Methods: Gene expression patterns from the Gene Expression Omnibus (GEO) database (GSE126209) were analyzed using weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) analysis, least absolute shrinkage and selection operator (LASSO) modeling, and survival analysis to identify charged multivesicular body protein 4C (CHMP4C). Subsequently, its role in regulating the immune system and immune cell infiltration was explored. CHMP4C expression and signaling molecules in OS were assessed in osteosarcoma cell lines (MG63, U2OS, HOS) and hFOB1.19 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The impact of CHMP4C upregulation and interference on OS-related signaling molecules in MG63 cells was studied. Functional validation of CHMP4C in MG63 OS cells was confirmed through cell counting Kit-8 (CCK-8), transwell, and colony formation assays. In vivo experiments were conducted using Specific Pathogen Free (SPF)-grade male BALB/C nude mice for OS xenograft studies.

Results: Based on the gene expression profiles analysis of six osteosarcoma samples and six normal tissue samples, we identified 1,511 upregulated DEGs and 5,678 downregulated DEGs in normal tissue samples. A significant positive correlation between the “yellow-green” module and OS was found through WGCNA analysis. Expression levels of CHMP4C, phosphorylated Glycogen Synthase Kinase 3β (p-GSK3β), and β-catenin were notably higher in U2OS, HOS, and MG63 OS cells than in hFOB1.19 human osteoblasts. Overexpressing CHMP4C in MG63 OS cells upregulated CHMP4C, p-GSK3β, and β-catenin while downregulating GSK3β, leading to increased proliferation and migration of MG63 cells. Conversely, interrupting CHMP4C had the opposite effect. High expression of CHMP4C significantly accelerated the growth of OS in nude mice, resulting in substantial upregulation of CHMP4C, p-GSK3β, and β-catenin expression and suppression of Glycogen Synthase Kinase 3β (GSK3β) expression in OS tissues.

Conclusion: CHMP4C may serve as a specific immunomodulatory gene for OS. Its activation of the Wnt/β-catenin signaling pathway, mainly by increasing the phosphorylation echelon of GSK3β, promotes the invasion and spread of OS.
β-delayed multiple-particle emitters minibeam radiation therapy: first dosimetric evaluation with Monte Carlo simulations
Authors: Corvino Angela , Schneider Tim , Prezado Yolanda
Published: April 2024

Radiation therapy, one of the most effective methods for cancer treatment, is still limited by the tolerances of normal tissues surrounding the tumor. Innovative techniques like spatially fractionated radiation therapy (SFRT) have been shown to increase normal tissue dose resistance. Heavy ions also offer high-dose conformity and increased relative biological effectiveness (RBE) when compared to protons and X-rays. The alliance of heavy ions and spatial fractionation of the dose has the potential to further increase the therapeutic index for difficult-to-treat cases today. In particular, the use of β-delayed multiple-particle emitters might further improve treatment response, as it holds the potential to increase high linear energy transfer (LET) decay products in the valleys of SFRT (low-dose regions) at the end of the range. To verify this hypothesis, this study compares β-delayed multiple-particle emitters (8Li, 9C, 31Ar) with their respective stable isotopes (7Li, 12C, 40Ar) to determine possible benefits of β-delayed multiple-particle emitters minibeam radiation therapy (β-MBRT). Monte Carlo simulations were performed using the GATE toolkit to assess the dose distributions of each ion. RBE-weighted dose distributions were calculated and used for the aforementioned comparison. No significant differences were found among carbon isotopes. In contrast, 8Li and 31Ar exhibited improved RBE-weighted dose distributions with an approximately 12–20% increase in the Bragg-peak-to-entrance dose ratio (BEDR) for both peaks and valleys, which favors tissue sparing. Additionally, 8Li and 31Ar exhibited a lower peak-to-valley dose ratio (PVDR) in normal tissues and higher PVDR in the tumor than 7Li and 40Ar. Biological experiments are needed to conclude whether the differences observed make β-delayed multiple-particle emitters advantageous for MBRT.
Exploring the interplay of trunk and shoulder rotation strength: a cross-sport analysis
Authors: Hank Mikulas , Miratsky Petr , Ford Kevin R. , Clarup Christian , Imal Osman , Verbruggen Ferdia Fallon , Zahalka Frantisek , Maly Tomas
Published: April 2024

Introduction: Trunk and shoulder strength are consistently shown to be involved in performance limitations, as well as contributing to stability, power output, and reducing the risk of injury. Although their biomechanical interaction is a critical aspect for athletes, there is limited research on the relationship between trunk and shoulder strength in sports where upper body mechanics are critical for optimal performance.

Purpose: This study examined the differences and relationships between trunk rotational strength and shoulder rotational strength among athletes participating in mixed martial arts (MMA), tennis, swimming, and baseball.

Methods: Maximal voluntary contraction tests were performed to evaluate strength of 39 professional adult male athletes from disciplines of MMA (n = 6), tennis (n = 11), swimming (n = 11) and baseball (n = 11). Peak force data were used in sports comparison and relationship analysis between trunk and shoulder rotation strength parameters.

Results: The findings revealed a complex and significant relationship between trunk and shoulder strength, with unique patterns for each athletic discipline. Tennis players exhibited a strong correlation between trunk bilateral differences and internal shoulder rotation, while other disciplines demonstrated a more balanced use of trunk asymmetry. Swimmers displayed the best interactions between trunk and shoulder overall, emphasizing the aquatic environment’s biomechanical demands. In MMA, the strongest correlation was between shoulder internal and external rotation with the trunk, mainly due to the number of defensive movements in addition to offensive ones. Baseball pitchers showed a significant correlation between internal/external shoulder rotation strength ratio and trunk asymmetry.

Conclusion: While no differences in peak force variables were found, unique relationships between trunk and shoulder rotational performance were discovered. The results suggest a long-term sport-specific adaptation of the trunk-shoulder interaction in sports that require upper limb power movements. It seems, that the relationship between the various parameters of trunk and shoulder was influenced by the movement stereotype of each sport. Therefore, recognition of sport-specific interactions is critical to the development of effective training programs that enhance performance and potentially reduce injury risk in different sports. Researchers and practitioners should focus on longitudinally monitoring fluctuations in TRS and SRS relationships throughout each sport season and examining potential associations with injury incidence.
Effects on growth performance and immunity of Monopterus albus after high temperature stress
Authors: Mao Yifan , Lv Weiwei , Huang Weiwei , Yuan Quan , Yang Hang , Zhou Wenzong , Li Mingyou
Published: April 2024

To investigate the impact of the effect of high temperature stimulation on Monopterus albus larvae after a certain period of time, five experimental groups were established at different temperatures. Then, the M. albus under high temperature stress was fed at 30°C for 70 days. After that, the growth index of the M. albus was counted and analyzed. In terms of growth index, high temperature stress had significant effects on FCR, FBW, WGR, and SGR of M. albus (p < 0.05). The SR increased after being stimulated by temperature (p < 0.1). The study revealed that liver cells of M. albus were harmed by elevated temperatures of 36°C and 38°C. In the experimental group, the activities of digestive enzymes changed in the same trend, reaching the highest point in the 32°C group and then decreasing, and the AMS activity in the 38°C group was significantly different from that in the 30°C group (p < 0.05). The activities of antioxidase in liver reached the highest at 34°C, which was significantly different from those at 30°C (p < 0.05). In addition, the expression levels of TLR1, C3, TNF-α, and other genes increased in the experimental group, reaching the highest point at 34°C, and the expression level of the IL-1β gene reached the highest point at 32°C, which was significantly different from that at 30°C (p < 0.05). However, the expression level of the IRAK3 gene decreased in the experimental group and reached its lowest point at 34°C (p < 0.05). The expression level of the HSP90α gene increased with the highest temperature stimulus and reached its highest point at 38°C (p < 0.05). In the α diversity index of intestinal microorganisms in the experimental group, the observed species, Shannon, and Chao1 indexes in the 34°C group were the highest (p < 0.05), and β diversity analysis revealed that the intestinal microbial community in the experimental group was separated after high temperature stimulation. At the phylum level, the three dominant flora are Proteus, Firmicutes, and Bacteroides. Bacteroides and Macrococcus abundance increased at the genus level, but Vibrio and Aeromonas abundance decreased. To sum up, appropriate high-temperature stress can enhance the immunity and adaptability of M. albus. These results show that the high temperature stimulation of 32°C–34°C is beneficial to the industrial culture of M. albus.
Do aluminum (Al)-hyperaccumulator and phosphorus (P)-solubilising species assist neighbouring plants sensitive to Al toxicity and P deficiency?
Authors: Delgado M. , Barra P. J. , Berrios G. , Mora M. L. , Durán P. , Valentine A. , Reyes-Díaz M.
Published: April 2024

We aimed to evaluate the facilitation effects of an aluminum (Al) hyperaccumulator species bearing cluster roots, Gevuina avellana, on the seedling growth and performance of an Al-intolerant and phosphorus (P)-deficient-sensitive plant, Vaccinium corymbosum. For this, seedlings of G. avellana and V. corymbosum were grown alone or together as follows: i) two G. avellana seedlings, ii) one G. avellana + one V. corymbosum and iii) two V. corymbosum, in soil supplemented with Al (as Al2(SO4)3) and in the control (without Al supplementation). We determined relative growth rate (RGR), photosynthetic rate, chlorophyll concentration, lipid peroxidation and Al and nutrient concentration [Nitrogen (N), P, potassium (K), calcium (Ca), magnesium (Mg), sodium (Na), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), and sulfur (S)] in leaves and roots of both species. The results showed that, in general, G. avellana did not assist V. corymbosum to enhance its RGR nor reduce its Al uptake. However, G. avellana assisted V. corymbosum in enhanced N acquisition and, consequently, to increase its chlorophyll concentration and photosynthetic rate. Besides, V. corymbosum had lower lipid peroxidation in leaves when grown in the soil with high Al supplementation in association with G. avellana. Our results suggest a facilitating effect of G. avellana to V. corymbosum when grown in soils with high Al concentration, by enhancing chlorophyll concentrations and photosynthetic rate, and decreasing the oxidative damage to lipids.
Tissue and cellular localization of condensed tannins in poplar roots and potential association with nitrogen uptake
Authors: Westley Rebecca , Ma Dawei , Hawkins Barbara J. , Constabel C. Peter
Published: April 2024

Condensed tannins are common in vegetative tissues of woody plants, including in roots. In hybrid poplar (Populus tremula x alba; also known as P. x canescens) CT assays indicated they were most concentrated in younger white roots and at the root tip. Furthermore, CT-specific staining of embedded tissue sections demonstrated accumulation in root cap cells and adjacent epidermal cells, as well as a more sporadic presence in cortex cells. In older, brown roots as well as roots with secondary growth (cork zone), CT concentration was significantly lower. The insoluble fraction of CTs was greatest in the cork zone. To determine if CT accumulation correlates with nutrient uptake in poplar roots, a microelectrode ion flux measurement (MIFE™) system was used to measure flux along the root axis. Greatest NH4+ uptake was measured near the root tip, but NO3- and Ca2+ did not vary along the root length. In agreement with earlier work, providing poplars with ample nitrogen led to higher accumulation of CTs across root zones. To test the functional importance of CTs in roots directly, CT-modified transgenic plants could be important tools.
Selenobacteria-mediated Se transformation and uptake involving the unique genetic code
Authors: Liao Qing , Li Ao-Mei , Xing Ying , Liang Pan-Xia , Jiang Ze-Pu , Liu Yong-Xian , Huang Dong-Liang
Published: April 2024

Selenium (Se) is a crucial micronutrient for human health. Plants are the primary source of Se for humans. Selenium in the soil serves as the primary source of Se for plants. The soil contains high total Se content in large areas in Guangxi, China. However, the available Se is low, hindering Se uptake by plants. Microorganisms play a pivotal role in the activation of Se in the soil, thereby enhancing its uptake by plants. In this study, selenobacteria were isolated from Se-rich soils in Guangxi. Then two selenobacteria strains, YLB1-6 and YLB2-1, representing the highest (30,000 μg/mL) and lowest (10,000 μg/mL) Se tolerance levels among the Se-tolerant bacteria, were selected for subsequent analysis. Although the two selenobacteria exhibited distinct effects, they can significantly transform Se species, resulting in a decrease in the soil residual Se (RES-Se) content while concurrently increasing the available Se (AVA-Se) content. Selenobacteria also enhance the transformation of Se valencies, with a significant increase observed in soluble Se6+ (SOL-Se6+). Additionally, selenobacteria can elevate the pH of acidic soil. Selenobacteria also promote the uptake of Se into plants. After treatment with YLB1-6 and YLB2-1, the Se content in the aboveground part of Chinese flowering cabbage increased by 1.96 times and 1.77 times, respectively, while the Se accumulation in the aboveground part of the plant significantly increased by 104.36% and 81.69%, respectively, compared to the control. Further whole-genome sequencing revealed the genetic difference between the two selenobacteria. Additionally, 46 and 38 candidate genes related to selenium utilization were identified from YLB1-6 and YLB2-1, respectively. This work accelerates our understanding of the potential molecular mechanism of Se biofortification by selenobacteria. It also provides microorganisms and gene targets for improving crop varieties or microorganisms to exploit the rich Se source in soil.