bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent development of polymer nanomicelles in the treatment of eye diseases
Authors: Cai Ruijun , Zhang Ling , Chi Hao
Published: August 2023

The eye, being one of the most intricate organs in the human body, hosts numerous anatomical barriers and clearance mechanisms. This highlights the importance of devising a secure and efficacious ocular medication delivery system. Over the past several decades, advancements have been made in the development of a nano-delivery platform based on polymeric micelles. These advancements encompass diverse innovations such as poloxamer, chitosan, hydrogel-encapsulated micelles, and contact lenses embedded with micelles. Such technological evolutions allow for sustained medication retention and facilitate enhanced permeation within the eye, thereby standing as the avant-garde in ocular medication technology. This review provides a comprehensive consolidation of ocular medications predicated on polymer nanomicelles from 2014 to 2023. Additionally, it explores the challenges they pose in clinical applications, a discussion intended to aid the design of future clinical research concerning ocular medication delivery formulations.
Umbilical cord mesenchymal stem cells for regenerative treatment of intervertebral disc degeneration
Authors: Huang Huagui , Liu Xin , Wang Jinzuo , Suo Moran , Zhang Jing , Sun Tianze , Zhang Wentao , Li Zhonghai
Published: August 2023

Intervertebral disc degeneration is thought to be a major contributor to low back pain, the etiology of which is complex and not yet fully understood. To compensate for the lack of drug and surgical treatment, mesenchymal stem cells have been proposed for regenerative treatment of intervertebral discs in recent years, and encouraging results have been achieved in related trials. Mesenchymal stem cells can be derived from different parts of the body, among which mesenchymal stem cells isolated from the fetal umbilical cord have excellent performance in terms of difficulty of acquisition, differentiation potential, immunogenicity and ethical risk. This makes it possible for umbilical cord derived mesenchymal stem cells to replace the most widely used bone marrow-derived and adipose tissue derived mesenchymal stem cells as the first choice for regenerating intervertebral discs. However, the survival of umbilical cord mesenchymal stem cells within the intervertebral disc is a major factor affecting their regenerative capacity. In recent years biomaterial scaffolds in tissue engineering have aided the survival of umbilical cord mesenchymal stem cells by mimicking the natural extracellular matrix. This seems to provide a new idea for the application of umbilical cord mesenchymal stem cells. This article reviews the structure of the intervertebral disc, disc degeneration, and the strengths and weaknesses of common treatment methods. We focus on the cell source, cell characteristics, mechanism of action and related experiments to summarize the umbilical cord mesenchymal stem cells and explore the feasibility of tissue engineering technology of umbilical cord mesenchymal stem cells. Hoping to provide new ideas for the treatment of disc degeneration.
Colchicine efficacy comparison at varying time points in the peri-operative period for coronary artery disease: a systematic review and meta-analysis of randomized controlled trials
Authors: Wei Zhi-Yang , Lai Jun-Yu , Li Ya-Ting , Yu Xiao-Yan , Liu Yan-Hong , Hu Jing-Xuan , Gao Bei-Bei , Wu Jian-Guang
Published: August 2023

Objectives

Over the years, it has been found that colchicine offers substantial benefits in secondary prevention in patients with coronary artery disease (CAD). We studied the effects of colchicine timing because there are no guidelines about when to provide it during the perioperative period for patients with CAD.

Methods

Up to January 1, 2023, seven electronic literature databases were screened (including three English databases and four Chinese databases). Randomized controlled trials included only treatment with colchicine in the perioperative period of CAD. The Cochrane Evaluation Tool was used to judge the risk of bias in research. Statistical analysis was performed by Stata 16.0 software.

Results

We evaluated twelve studies that found colchicine to be effective in decreasing the occurrence of major adverse cardiac events (MACEs) (p < 0.00001), but it also raised the rate of adverse events (p = 0.001). Subgroup analysis showed the same benefit in lowering the incidence of MACE with continuous administration of a total daily dose of 0.5 mg postoperatively while minimizing drug-related side effects in the patients (p = 0.03). When it comes to preventing surgical stroke occurrences, postoperative administration is more effective (p = 0.006). While the effect of simultaneous preoperative and postoperative administration was marginally greater than other periods in reducing postoperative hs-CRP levels (p = 0.02).

Conclusion

Colchicine, a traditional anti-inflammatory drug, also reduces the risk of MACE by reducing inflammation after PCI. Administration at different periods had no significant effect on decreasing the occurrence of MACE, but when administered postoperatively, we advise continuous administration with a total daily dose of 0.5 mg to obtain the same benefit while minimizing the drug's side effects. Postoperative administration is the better measure to prevent postoperative stroke events. Due to the effective anti-inflammatory effect of colchicine, we recommend its use as early as possible in the perioperative period and its continued use at low doses in the postoperative period.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316751, identifier CRD42022316751.
Baseline fibroblast growth factor 23 is associated with long-term mortality in ST-elevation myocardial infarction—results from the augsburg myocardial infarction registry
Authors: Schmitz Timo , Wein Bastian , Heier Margit , Peters Annette , Meisinger Christa , Linseisen Jakob
Published: August 2023

Background

The aim of this study was to investigate the association between inflammatory plasma protein concentrations and long-term mortality in patients with ST-elevation myocardial infarction (STEMI).

Methods

For 343 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 inflammatory plasma proteins were measured at the index event using the OLINK inflammation panel. In multivariable-adjusted Cox regression models, the association between each plasma protein and all-cause long-term mortality was investigated. Median follow-up time was 7.6 (IQR: 2.4) years. For plasma protein that showed a strong association with long-term mortality, a 5-year survival ROC analysis was performed.

Results

One plasma protein, namely Fibroblast Growth Factor 23 (FGF-23), was particularly well associated with long-term mortality in the multivariable-adjusted Cox model with an FDR-adjusted p-value of <0.001 and a Hazard Ratio (HR) of 1.57 [95% CI: 1.29–1.91]. In the 5-years ROC analysis, an AUC of 0.6903 [95% CI: 0.594–0.781] was estimated for FGF-23. All other plasma protein didńt show strong associations, each marker with FDR-adjusted p-values >0.05 in the multivariable-adjusted Cox models.

Conclusions

FGF-23 is independently associated with long-term mortality after STEMI and might play an important role in the response to myocardial injury. The results suggest FGF-23 to be a useful marker in the long-term treatment of STEMI patients and a potential target for drug development.
Direct solar FTIR measurements of CO2 and HCl in the plume of Popocatépetl Volcano, Mexico
Authors: Stremme Wolfgang , Grutter Michel , Baylón Jorge , Taquet Noemie , Bezanilla Alejandro , Plaza-Medina Eddy , Schiavo Benedetto , Rivera Claudia , Blumenstock Thomas , Hase Frank
Published: August 2023

Volcanic CO2 emissions inventories have great importance in the understanding of the geological carbon cycle. Volcanoes provide the primary pathway for solid-earth volatiles to reach the Earth’s atmosphere and have the potential to significantly contribute to the carbon-climate feedback. Volcanic carbon emissions (both passive and eruptive degassing) included in inventories, largely stem from patchy surface measurements that suffer from difficulties in removing the atmospheric background. With a 27-year-long ongoing open-vent eruption, Popocatépetl ranks as one of the highest permanent volcanic CO2 emitters worldwide and provides an excellent natural laboratory to design and experiment with new remote sensing methods for volcanic gas emission measurements. Since October 2012, infrared spectra at different spectral regions have been recorded with a solar occultation FTIR spectrometer. The near-infrared spectra allow for high precision measurements of CO2 and HCl columns. Under favorable conditions, the continuous observations during sunrise allow the reconstruction of a plume cross-section of HCl and the estimation of the emission flux using wind data. Despite that the detection of CO2 is more challenging, on April 26th, 2015 we captured a volcanic plume under favourable wind conditions which allowed us to reconstruct from this particular event a CO2 emission rate of 116.10 ± 17.2 kg/s. The volcanic HCl emission on this event was the highest detected during the 2012-2016 period. An annual average CO2 emission estimate of (41.2 ± 16.7) kg/s ((1.30 ± 0.53) Tg/yr) could be determined from a statistical treatment of the detected CO2 and HCl columns in the IR spectra, and their corresponding molecular ratios, during this period. A total of 25 events were used to derive a mean CO2/HCl molecule ratio of 11.4 ± 4.4 and an average HCl emission rate of (3.0 ± 0.3) kg/s could be determined. The CO2 emissions of Popocatépetl were found to be around 0.32% of the total anthropogenic CO2 emissions reported in the country and 3.6% of those corresponding to the Mexico City Metropolitan Area (MCMA). CO2 emissions from the Popocatépetl volcano can be considered to play a negligible role in the global CO2 budget, but should be taken into account.
Hypoparathyroidism, deafness and renal dysplasia syndrome caused by a GATA3 splice site mutation leading to the activation of a cryptic splice site
Authors: Gonçalves Catarina I. , Carriço Josianne N. , Omar Omneya M. , Abdalla Ebtesam , Lemos Manuel C.
Published: August 2023

The HDR syndrome is a rare autosomal dominant disorder characterised by Hypoparathyroidism, Deafness, and Renal dysplasia, and is caused by inactivating heterozygous germline mutations in the GATA3 gene. We report an 11-year-old girl with HDR syndrome caused by a heterozygous mutation located at the splice acceptor site of exon 5 of the GATA3 gene (NM_001002295.2: c.925-1G>T). Functional studies using a minigene assay showed that this splice site mutation abolished the normal splicing of the GATA3 pre-mRNA and led to the use of a cryptic splice acceptor site, resulting in the loss of the first seven nucleotides (TCTGCAG) of exon 5 in the GATA3 mRNA. These findings increase the understanding of the mechanisms by which GATA3 splicing mutations can cause HDR syndrome.
Inter-industrial embodied carbon transfers in a developed subnational region: a case study of Guangdong Province, China
Authors: Liu Wei , Ji Junping , Liu Xin
Published: August 2023

The close production and consumption relationship between industries leads to the embodied CO2 transfer among industrial sectors along with the exchange of products. Thus, grasping the situation of embodied carbon transfers from the demand side is of great significance for better reducing a country or region’s CO2 emissions. This study investigates the embodied carbon transfers in Guangdong Province from 2002 to 2017 from the industrial dimension by applying a hypothetical extraction method. An enhanced generalized RAS method was utilized to predict the intersectoral carbon transfers in 2025 and 2030. The results show that, from 2002 to 2017, the average proportion of carbon emission output of 72.11% made the production and supply of electricity and heat sector the main CO2 emission transfer exporter, while the other service and construction sectors were the leading importers. Moreover, the embodied carbon transfers between these three sectors are the main carbon transfer paths. By 2025, the other service sectors will become the largest embodied carbon importers, surpassing the construction sector. Therefore, it is necessary to control the consumption demand of other service and construction sectors on the demand side to reduce carbon emissions driven by demand.
Accuracy and inter-cloud precision of low-cost mobile LiDAR technology in estimating soil disturbance in forest operations
Authors: Forkuo Gabriel Osei , Borz Stelian Alexandru
Published: August 2023

Forest operations can cause long-term soil disturbance, leading to environmental and economic losses. Mobile LiDAR technology has become increasingly popular in forest management for mapping and monitoring disturbances. Low-cost mobile LiDAR technology, in particular, has attracted significant attention due to its potential cost-effectiveness, ease of use, and ability to capture high-resolution data. The LiDAR technology, which is integrated in the iPhone 13–14 Pro Max series, has the potential to provide high accuracy and precision data at a low cost, but there are still questions on how this will perform in comparison to professional scanners. In this study, an iPhone 13 Pro Max equipped with SiteScape and 3D Scanner apps, and the GeoSlam Zeb Revo scanner were used to collect and generate point cloud datasets for comparison in four plots showing variability in soil disturbance and local topography. The data obtained from the LiDAR devices were analyzed in CloudCompare using the Iterative Closest Point (ICP) and Least Square Plane (LSP) methods of cloud-to-cloud comparisons (C2C) to estimate the accuracy and intercloud precision of the LiDAR technology. The results showed that the low-cost mobile LiDAR technology was able to provide accurate and precise data for estimating soil disturbance using both the ICP and LSP methods. Taking as a reference the point clouds collected with the Zeb Revo scanner, the accuracy of data derived with SiteScape and 3D Scanner apps varied from RMS = 0.016 to 0.035 m, and from RMS = 0.017 to 0.025 m, respectively. This was comparable to the precision or repeatability of the professional LiDAR instrument, Zeb Revo (RMS = 0.019–0.023 m). The intercloud precision of the data generated with SiteScape and 3D Scanner apps varied from RMS = 0.015 to 0.017 m and from RMS = 0.012 to 0.014 m, respectively, and were comparable to the precision of Zeb Revo measurements (RMS = 0.019–0.023 m). Overall, the use of low-cost mobile LiDAR technology fits well to the requirements to map and monitor soil disturbances and it provides a cost-effective and efficient way to gather high resolution data, which can assist the sustainable forest management practices.
Extracellular Vesicles-mediated recombinant IL-10 protects against ascending infection-associated preterm birth by reducing fetal inflammatory response
Authors: Kammala Ananth Kumar , Mosebarger Angela , Radnaa Enkhtuya , Rowlinson Emma , Vora Natasha , Fortunato Stephen J. , Sharma Surendra , Safarzadeh Melody , Menon Ramkumar
Published: August 2023

Background

Fetal inflammatory response mediated by the influx of immune cells and activation of pro-inflammatory transcription factor NF-κB in feto-maternal uterine tissues is the major determinant of infection-associated preterm birth (PTB, live births < 37 weeks of gestation).

Objective

To reduce the incidence of PTB by minimizing inflammation, extracellular vesicles (EVs) were electroporetically engineered to contain anti-inflammatory cytokine interleukin (IL)-10 (eIL-10), and their efficacy was tested in an ascending model of infection (vaginal administration of E. coli) induced PTB in mouse models.

Study design

EVs (size: 30-170 nm) derived from HEK293T cells were electroporated with recombinant IL-10 at 500 volts and 125 Ω, and 6 pulses to generate eIL-10. eIL-10 structural characters (electron microscopy, nanoparticle tracking analysis, ExoView [size and cargo content] and functional properties (co-treatment of macrophage cells with LPS and eIL-10) were assessed. To test efficacy, CD1 mice were vaginally inoculated with E. coli (1010CFU) and subsequently treated with either PBS, eIL-10 (500ng) or Gentamicin (10mg/kg) or a combination of eIL-10+gentamicin. Fetal inflammatory response in maternal and fetal tissues after the infection or treatment were conducted by suspension Cytometer Time of Flight (CyTOF) using a transgenic mouse model that express red fluorescent TdTomato (mT+) in fetal cells.

Results

Engineered EVs were structurally and functionally stable and showed reduced proinflammatory cytokine production from LPS challenged macrophage cells in vitro. Maternal administration of eIL-10 (10 µg/kg body weight) crossed feto-maternal barriers to delay E. coli-induced PTB to deliver live pups at term. Delay in PTB was associated with reduced feto-maternal uterine inflammation (immune cell infiltration and histologic chorioamnionitis, NF-κB activation, and proinflammatory cytokine production).

Conclusions

eIL-10 administration was safe, stable, specific, delayed PTB by over 72 hrs and delivered live pups. The delivery of drugs using EVs overcomes the limitations of in-utero fetal interventions. Protecting IL-10 in EVs eliminates the need for the amniotic administration of recombinant IL-10 for its efficacy.
The off-target effects of AID in carcinogenesis
Authors: Jiao Junna , Lv Zhuangwei , Wang Yurong , Fan Liye , Yang Angang
Published: August 2023

Activation-induced cytidine deaminase (AID) plays a crucial role in promoting B cell diversification through somatic hypermutation (SHM) and class switch recombination (CSR). While AID is primarily associated with the physiological function of humoral immune response, it has also been linked to the initiation and progression of lymphomas. Abnormalities in AID have been shown to disrupt gene networks and signaling pathways in both B-cell and T-cell lineage lymphoblastic leukemia, although the full extent of its role in carcinogenesis remains unclear. This review proposes an alternative role for AID and explores its off-target effects in regulating tumorigenesis. In this review, we first provide an overview of the physiological function of AID and its regulation. AID plays a crucial role in promoting B cell diversification through SHM and CSR. We then discuss the off-target effects of AID, which includes inducing mutations of non-Igs, epigenetic modification, and the alternative role as a cofactor. We also explore the networks that keep AID in line. Furthermore, we summarize the off-target effects of AID in autoimmune diseases and hematological neoplasms. Finally, we assess the off-target effects of AID in solid tumors. The primary focus of this review is to understand how and when AID targets specific gene loci and how this affects carcinogenesis. Overall, this review aims to provide a comprehensive understanding of the physiological and off-target effects of AID, which will contribute to the development of novel therapeutic strategies for autoimmune diseases, hematological neoplasms, and solid tumors.
Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy
Authors: Zheng Zhuangzhuang , Su Jing , Bao Xueying , Wang Huanhuan , Bian Chenbin , Zhao Qin , Jiang Xin
Published: August 2023

Radiotherapy (RT) is an effective treatment option for cancer patients, which induces the production of reactive oxygen species (ROS) and causes oxidative stress (OS), leading to the death of tumor cells. OS not only causes apoptosis, autophagy and ferroptosis, but also affects tumor immune response. The combination of RT and immunotherapy has revolutionized the management of various cancers. In this process, OS caused by ROS plays a critical role. Specifically, RT-induced ROS can promote the release of tumor-associated antigens (TAAs), regulate the infiltration and differentiation of immune cells, manipulate the expression of immune checkpoints, and change the tumor immune microenvironment (TME). In this review, we briefly summarize several ways in which IR induces tumor cell death and discuss the interrelationship between RT-induced OS and antitumor immunity, with a focus on the interaction of ferroptosis with immunogenic death. We also summarize the potential mechanisms by which ROS regulates immune checkpoint expression, immune cells activity, and differentiation. In addition, we conclude the therapeutic opportunity improving radiotherapy in combination with immunotherapy by regulating OS, which may be beneficial for clinical treatment.
Saccharomyces boulardii CNCM I-745 supplementation during and after antibiotic treatment positively influences the bacterial gut microbiota
Authors: Spatz Madeleine , Wang Yazhou , Lapiere Alexia , Da Costa Gregory , Michaudel Chloé , Danne Camille , Michel Marie-Laure , Langella Philippe , Sokol Harry , Richard Mathias L.
Published: August 2023

Introduction

Antibiotic effects on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the mycobiota, the fungal part of the microbiota and how the length of administration influences both microbiota. Here, we examined the effect of antibiotics (ATB) on the composition of bacterial and fungal microbiota and how the administration of Saccharomyces boulardii CNCM I-745 influences both microbiota.

Methods

In order to get closer to the human microbiota, the mice used in this study were subjected to fecal microbiota transfer (FMT) using human feces and subsequently called human microbiotaassociated (HMA) mice. These mice were then treated with amoxicillinclavulanate antibiotics and supplemented with S. boulardii during and after ATB treatment to understand the effect of the yeast probiotic on both bacterial and fungal microbiota. Bacterial and fungal microbiota analyses were done using 16S and ITS2 rRNA amplicon-based sequencing.

Results

We showed that the administration of S. boulardii during ATB treatment had very limited effect on the fungal populations on the long term, once the yeast probiotic has been cleared from the gut. Concerning bacterial microbiota, S. boulardii administration allowed a better recovery of bacterial populations after the end of the ATB treatment period. Additionally, 16S and ITS2 rRNA sequence analysis revealed that 7 additional days of S. boulardii administration (17 days in total) enhanced the return of the initial bacterial equilibrium.

Discussion

In this study, we provide a comprehensive analysis of how probiotic yeast administration can influence the fungal and bacterial microbiota in a model of broad-spectrum antibiotherapy.
Functional analysis of CTLA4 promoter variant and its possible implication in colorectal cancer immunotherapy
Authors: Angulo-Aguado Mariana , Orjuela-Amarillo Sarah , Mora-Jácome Julián Francisco , Córdoba Lea Paloma , Gallego-Ortiz Antonio , Gaviria-Sabogal Cristian Camilo , Contreras Nora , Figueroa Carlos , Ortega-Recalde Oscar , Morel Adrien , Fonseca-Mendoza Dora Janeth
Published: August 2023

Background

Colorectal cancer (CRC) is a prevalent cancer, ranking as the third most common. Recent advances in our understanding of the molecular causes of this disease have highlighted the crucial role of tumor immune evasion in its initiation and progression. CTLA4, a receptor that acts as a negative regulator of T cell responses, plays a pivotal role in this process, and genetic variations in CTLA4 have been linked to CRC susceptibility, prognosis, and response to therapy.

Methods

We conducted a case-control study involving 98 CRC patients and 424 controls. We genotyped the CTLA4 c.-319C > T variant (rs5742909) and performed an association analysis by comparing allele frequencies between the patients and controls. To assess the potential functional impact of this variant, we first performed an In Silico analysis of transcription factor binding sites using Genomatix. Finally, to validate our findings, we conducted a luciferase reporter gene assay using different cell lines and an electrophoretic mobility shift assay (EMSA).

Results

The case-control association analysis revealed a significant association between CTLA4 c.-319C > T and CRC susceptibility (p = 0.023; OR 1.89; 95% CI = 1.11–3.23). Genomatix analysis identified LEF1 and TCF7 transcription factors as specific binders to CTLA4 c.-319C. The reporter gene assay demonstrated notable differences in luciferase activity between the c.-319 C and T alleles in COS-7, HCT116, and Jurkat cell lines. EMSA analysis showed differences in TCF7 interaction with the CTLA4 C and T alleles.

Conclusion

CTLA4 c.-319C > T is associated with CRC susceptibility. Based on our functional validation results, we proposed that CTLA4 c.-319C > T alters gene expression at the transcriptional level, triggering a stronger negative regulation of T-cells and immune tumoral evasion.
Four-dimensional computed tomography detects dynamic three-dimensional pathologies of the wrist in patients with calcium pyrophosphate deposition disease
Authors: Ulas Sevtap Tugce , Pochandke Louise , Ohrndorf Sarah , Diekhoff Torsten , Ziegeler Katharina
Published: August 2023

Objectives

Crystal deposits in ligaments of the wrist are typical findings in patients with calcium pyrophosphate deposition (CPPD) disease. CPPD crystals trigger inflammation and ultimately result in ligament tears with scapholunate (SL) advanced collapse (SLAC). This study aimed to investigate carpal instabilities in patients with CPPD using four-dimensional computed tomography (4D-CT) of the wrist.

Methods

This IRB-approved prospective feasibility study investigated patients with CPPD of the hand. All patients underwent a static 3D-CT and two dynamic 4D-CT in ulnar- and radial abduction and in supination and pronation movements to analyze instabilities of the SL region and of the distal radioulnar joint (DRUJ). Two independent readers scored the images for the presence of SL ligament and triangular fibrocartilage complex (TFCC) calcifications. Furthermore, the readers assessed the dynamic images for SL and DRUJ instabilities. Descriptive analyses were performed. Inter-rater reliability was assessed using Cohen’s kappa (κ).

Results

Nine patients were included. SL ligament calcifications and instabilities were found in all patients. Of these, dynamic SL instability was detected in 77.8% of the patients, while 22.2% had a SLAC wrist. TFCC calcifications were found in 87.5% of the patients. Four patients had DRUJ instability (50%). No patient showed DRUJ instability without the presence of TFCC calcifications. Agreement between readers for calcifications was excellent (κ = 1) and almost perfect (κ = 0.89) for instabilities.

Conclusion

This study provides the first evidence of relevant dynamic carpal instability in CPPD patients using advanced imaging techniques with 4D-CT, offering unique insights into wrist biomechanics.
Enhancing plant defense using rhizobacteria in processing tomatoes: a bioprospecting approach to overcoming Early Blight and Alternaria toxins
Authors: Bellotti Gabriele , Guerrieri Maria Chiara , Giorni Paola , Bulla Giulia , Fiorini Andrea , Bertuzzi Terenzio , Antinori Maria Elena , Puglisi Edoardo
Published: August 2023

Plant growth-promoting rhizobacteria (PGPR) with antagonistic activity toward plant pathogenic fungi are valuable candidates for the development of novel plant protection products based on biocontrol activity. The very first step in the formulation of such products is to screen the potential effectiveness of the selected microorganism(s). In this study, non-pathogenic rhizobacteria were isolated from the rhizosphere of tomato plants and evaluated for their biocontrol activity against three species of mycotoxin-producing Alternaria. The assessment of their biocontrol potential involved investigating both fungal biomass and Alternaria toxin reduction. A ranking system developed allowed for the identification of the 12 best-performing strains among the initial 85 isolates. Several rhizobacteria showed a significant reduction in fungal biomass (up to 76%) and/or mycotoxin production (up to 99.7%). Moreover, the same isolates also demonstrated plant growth-promoting (PGP) traits such as siderophore or IAA production, inorganic phosphate solubilization, and nitrogen fixation, confirming the multifaceted properties of PGPRs. Bacillus species, particularly B. amyloliquefaciens and two strains of B. subtilis, showed the highest efficacy in reducing fungal biomass and were also effective in lowering mycotoxin production. Isolates such as Enterobacter ludwigii, Enterobacter asburiae, Serratia nematodiphila, Pantoea agglomerans, and Kosakonia cowanii showed moderate efficacy. Results suggest that by leveraging the diverse capabilities of different microbial strains, a consortium-based approach would provide a broader spectrum of effectiveness, thereby signaling a more encouraging resolution for sustainable agriculture and addressing the multifaceted nature of crop-related biotic challenges.
Rare phylotypes in stone, stool, and urine microbiomes are associated with urinary stone disease
Authors: Suryavanshi Mangesh , Agudelo Jose , Miller Aaron
Published: August 2023

Introduction: In complex microbial communities, the importance of microbial species at very low abundance levels and their prevalence for overall community structure and function is increasingly being recognized. Clinical microbiome studies on urinary stone disease (USD) have indicated that both the gut and urinary tract microbiota are associated with the onset of the disease and that kidney stones them-selves harbor a complex, yet consistent and viable, microbiome. However, how rare phylotypes contribute to this association remains unclear. Delineating the contribution of rare and common phylotypes to urinary stone disease is important for the development of bacteriotherapies to promote urologic health.

Methods: The objectives of the current report were to conduct a metaanalysis of 16S rRNA datasets derived from the kidney stone, stool, and urine samples of participants with or without urinary stone disease. To delineate the impact of rare and common phylotypes, metaanalyses were conducted by first separating rare and common taxa determined by both the frequency and abundance of amplicon sequence variants.

Results: Consistent with previous analyses, we found that gut, upper urinary, and lower urinary tract microbiomes were all unique. Rare phylotypes comprised the majority of species observed in all sample types, with kidney stones exhibiting the greatest bias toward rarity, followed by urine and stool. Both rare and common fractions contributed significantly to the differences observed between sample types and health disparity. Furthermore, the rare and common fractions were taxonomically unique across all sample types. A total of 222 and 320 unique rare phylotypes from urine and stool samples were found to be significantly associated with USD. A co-occurrence correlation analysis revealed that rare phylotypes are most important for microbiome structure in stones, followed by urine and stool.

Discussion: Collectively, the results indicate that rare phylotypes may be important for the pathophysiology of USD, particularly in the kidney stone matrix, which is inherently a very low microbial biomass niche that can have implications for the diagnosis and treatment of kidney stones. Further studies are needed to investigate the functional significance of rare phylotypes in kidney stone pathogenesis.
Emerging role of exosome-derived non-coding RNAs in tumor-associated angiogenesis of tumor microenvironment
Authors: Duan Sai-Li , Fu Wei-Jie , Jiang Ying-Ke , Peng Lu-Shan , Ousmane Diabate , Zhang Zhe-Jia , Wang Jun-Pu
Published: August 2023

The tumor microenvironment (TME) is an intricate ecosystem that is actively involved in various stages of cancer occurrence and development. Some characteristics of tumor biological behavior, such as proliferation, migration, invasion, inhibition of apoptosis, immune escape, angiogenesis, and metabolic reprogramming, are affected by TME. Studies have shown that non-coding RNAs, especially long-chain non-coding RNAs and microRNAs in cancer-derived exosomes, facilitate intercellular communication as a mechanism for regulating angiogenesis. They stimulate tumor growth, as well as angiogenesis, metastasis, and reprogramming of the TME. Exploring the relationship between exogenous non-coding RNAs and tumor-associated endothelial cells, as well as their role in angiogenesis, clinicians will gain new insights into treatment as a result.
Multiple cross-frequency coupling analysis of resting-state EEG in patients with mild cognitive impairment and Alzheimer’s disease
Authors: Chen Xi , Li Yingjie , Li Renren , Yuan Xiao , Liu Meng , Zhang Wei , Li Yunxia
Published: August 2023

Introduction

Electroencephalographic (EEG) abnormalities are seen in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) with characteristic features of cognitive impairment. The most common findings of EEG features in AD and MCI patients are increased relative power of slow oscillations (delta and theta rhythms) and decreased relative power of fast oscillations (alpha, beta and gamma rhythms). However, impairments in cognitive processes in AD and MCI are not sufficiently reflected by brain oscillatory activity in a particular frequency band. MCI patients are at high risk of progressing to AD. Cross-frequency coupling (CFC), which refers to coupling between different frequency bands, is a crucial tool for comprehending changes in brain oscillations and cognitive performance. CFC features exhibit some specificity in patients with AD and MCI, but a comparison between CFC features in individuals with these disorders is still lacking. The aim of this study was to explore changes in CFC properties in MCI and AD and to explore the relationship between CFC properties and multiple types of cognitive functional performance.

Methods

We recorded resting-state EEG (rsEEG) signals in 46 MCI patients, 43 AD patients, and 43 cognitively healthy controls (HCs) and analyzed the changes in CFC as well as the relationship between CFC and scores on clinical tests of cognitive function.

Results and discussion

Multiple couplings between low-frequency oscillations and high-frequency oscillations were found to be significantly enhanced in AD patients compared to those of HCs and MCI, while delta-gamma as well as theta-gamma couplings in the right temporal and parietal lobes were significantly enhanced in MCI patients compared to HCs. Moreover, theta-gamma coupling in the right temporal lobe tended to be stronger in MCI patients than in HCs, and it was stronger in AD than in MCI. Multiple CFC properties were found to correlate significantly with various cognitive domains, especially the memory function domain. Overall, these findings suggest that AD and MCI patients must use more neural resources to maintain a resting brain state and that alterations in theta-gamma coupling in the temporal lobe become progressively obvious during disease progression and are likely to be a valuable indicator of MCI and AD pathology.
Therapeutic and prognostic features in myasthenia gravis patients followed in a tertiary neuromuscular diseases center in Turkey
Authors: Yaman Aylin , Kurtuluş Aydın Fatma
Published: August 2023

Introduction

In this study, we aim to evaluate the treatment responses and prognostic characteristics of Myasthenia Gravis (MG) patients followed in a tertiary neuromuscular diseases center in Turkey.

Methods

One hundred seventy four MG patients (between years 2011 and 2022) in Antalya, Turkey were diagnosed, and evaluated on a classification of MG was based on Myasthenia. Gravis Foundation of America (MGFA) clinical classification. Exclusion of other possible diseases in the differential diagnosis and support by beneficial response to treatment with acetylcholinesterase inhibitors were also taken into consideration.

Results

Mean age of participants was 54.86 (SD = 14.856; min-max = 22–84). Ninety (51.7%) were female. MG was more common in women under the age of 65 (58%) and in men over the age of 65 (64%). Generalized MG was seen in 75.3% of the patients. Anti-AChR positivities were detected in 52.3%, Anti-MuSK positivity in 4.6%, and seronegativity in 22.4%. Thymoma was detected in nearly 9.8% and thymectomy was performed in 28.7 percent. Most of the patients (57.5%) were using corticosteroids. Azathioprine was used by 39% and mycophenolate mofetil by 10.3% of patients. Mortality was higher and disease was more severe in late-onset (>50 years) MG patients (especially in the COVID-19 pandemic). Eight patients (four women, four men, mean age 75.5 years) died during follow-up. None of them died due to myasthenic worsening, two died due to malignancy and two due to infection. During the COVID pandemic, 16 patients (9.2%) had COVID infection. Four patients died due to COVID-19 infection, these four patients had serious comorbidities, and three of them were elderly (>75 years).

Conclusion

In conclusion, MG is more common in women between the ages of 20–40 and in men over the age of 65. The use of corticosteroids was more common under the age of 50, and the use of non-steroidal immunosuppressant agents was more common over the age of 50. Thymectomy is still an important supportive treatment approach in anti-AChR positive and seronegative generalized patients under 50 years of age. IVIG and plasmapheresis are effective treatments during acute exacerbations and bridging periods of treatments. Specific treatments are needed especially for resistant group of patients.
FcRN receptor antagonists in the management of myasthenia gravis
Authors: Bhandari Vinaya , Bril Vera
Published: August 2023

Myasthenia gravis (MG) is an autoimmune disorder characterized by autoantibodies specifically directed against proteins located within the postsynaptic membrane of the neuromuscular junction. These pathogenic autoantibodies can be reduced by therapies such as plasma exchange, IVIG infusions and other immunosuppressive agents. However, there are significant side effects associated with most of these therapies. Since there is a better understanding of the molecular structure and the biological properties of the neonatal Fc receptors (FcRn), it possesses an attractive profile in treating myasthenia gravis. FcRn receptors prevent the catabolism of IgG by impeding their lysosomal degradation and facilitating their extracellular release at physiological pH, consequently extending the IgG half-life. Thus, the catabolism of IgG can be enhanced by blocking the FcRn, leading to outcomes similar to those achieved through plasma exchange with no significant safety concerns. The available studies suggest that FcRn holds promise as a versatile therapeutic intervention, capable of delivering beneficial outcomes in patients with distinct characteristics and varying degrees of MG severity. Efgartigimod is already approved for the treatment of generalized MG, rozanolixizumab is under review by health authorities, and phase 3 trials of nipocalimab and batoclimab are underway. Here, we will review the available data on FcRn therapeutic agents in the management of MG.
Effects of oral intake fruit or fruit extract on skin aging in healthy adults: a systematic review and Meta-analysis of randomized controlled trials
Authors: Li Haoying , Wang Lu , Feng Jinhong , Jiang Lijuan , Wu Jingping
Published: August 2023

Background

In recent years, oral various fruits or supplements of fruits natural extracts have been reported to have significant anti-aging effects on the skin (1, 2), However, despite many studies on this topic, there is often no clear evidence to support their efficacy and safety. In this paper, we present a comprehensive review and Meta-analysis of the evidence for the safety and efficacy of oral fruits and fruits extracts in improving skin aging.

Methods

Four databases, Pubmed, Embase, Web of Science, and Cochrane Library (CENTRAL), were searched for relevant literature from 2000–01 to 2023–03. Seven randomized controlled trials (RCTs) of fruit intake or fruit extracts associated with anti-skin aging were screened for Meta-analysis.

Results

Compared to placebo, oral intake of fruit or fruit extracts showed significant statistical differences in skin hydration and transepidermal water loss (TEWL), with a significant improvement in skin hydration and a significant decrease in TEWL. No significant statistical difference was observed in minimal erythema dose (MED), overall skin elasticity (R2), or wrinkle depth, and no evidence of significant improvement in skin condition was observed.

Conclusion

Meta-analysis results suggest that consume administration of fruits or fruit extracts significantly enhances skin hydration and reduces transcutaneous water loss, but there is insufficient evidence to support other outcome recommendations, including minimal erythema dose (MED), overall skin elasticity(R2), and wrinkle depth.

Systematic Review Registration

PROSPERO (york.ac.uk), identifier CRD42023410382.
A deep learning approach for automatic tumor delineation in stereotactic radiotherapy for non-small cell lung cancer using diagnostic PET-CT and planning CT
Authors: Yu Xuyao , He Lian , Wang Yuwen , Dong Yang , Song Yongchun , Yuan Zhiyong , Yan Ziye , Wang Wei
Published: August 2023

Introduction

Accurate delineation of tumor targets is crucial for stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). This study aims to develop a deep learning-based segmentation approach to accurately and efficiently delineate NSCLC targets using diagnostic PET-CT and SBRT planning CT (pCT).

Methods

The diagnostic PET was registered to pCT using the transform matrix from registering diagnostic CT to the pCT. We proposed a 3D-UNet-based segmentation method to segment NSCLC tumor targets on dual-modality PET-pCT images. This network contained squeeze-and-excitation and Residual blocks in each convolutional block to perform dynamic channel-wise feature recalibration. Furthermore, up-sampling paths were added to supplement low-resolution features to the model and also to compute the overall loss function. The dice similarity coefficient (DSC), precision, recall, and the average symmetric surface distances were used to assess the performance of the proposed approach on 86 pairs of diagnostic PET and pCT images. The proposed model using dual-modality images was compared with both conventional 3D-UNet architecture and single-modality image input.

Results

The average DSC of the proposed model with both PET and pCT images was 0.844, compared to 0.795 and 0.827, when using 3D-UNet and nnUnet. It also outperformed using either pCT or PET alone with the same network, which had DSC of 0.823 and 0.732, respectively.

Discussion

Therefore, our proposed segmentation approach is able to outperform the current 3D-UNet network with diagnostic PET and pCT images. The integration of two image modalities helps improve segmentation accuracy.
Proposing new early detection indicators for pancreatic cancer: Combining machine learning and neural networks for serum miRNA-based diagnostic model
Authors: Chi Hao , Chen Haiqing , Wang Rui , Zhang Jieying , Jiang Lai , Zhang Shengke , Jiang Chenglu , Huang Jinbang , Quan Xiaomin , Liu Yunfei , Zhang Qinhong , Yang Guanhu
Published: August 2023

Background

Pancreatic cancer (PC) is a lethal malignancy that ranks seventh in terms of global cancer-related mortality. Despite advancements in treatment, the five-year survival rate remains low, emphasizing the urgent need for reliable early detection methods. MicroRNAs (miRNAs), a group of non-coding RNAs involved in critical gene regulatory mechanisms, have garnered significant attention as potential diagnostic and prognostic biomarkers for pancreatic cancer (PC). Their suitability stems from their accessibility and stability in blood, making them particularly appealing for clinical applications.

Methods

In this study, we analyzed serum miRNA expression profiles from three independent PC datasets obtained from the Gene Expression Omnibus (GEO) database. To identify serum miRNAs associated with PC incidence, we employed three machine learning algorithms: Support Vector Machine-Recursive Feature Elimination (SVM-RFE), Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest. We developed an artificial neural network model to assess the accuracy of the identified PC-related serum miRNAs (PCRSMs) and create a nomogram. These findings were further validated through qPCR experiments. Additionally, patient samples with PC were classified using the consensus clustering method.

Results

Our analysis revealed three PCRSMs, namely hsa-miR-4648, hsa-miR-125b-1-3p, and hsa-miR-3201, using the three machine learning algorithms. The artificial neural network model demonstrated high accuracy in distinguishing between normal and pancreatic cancer samples, with verification and training groups exhibiting AUC values of 0.935 and 0.926, respectively. We also utilized the consensus clustering method to classify PC samples into two optimal subtypes. Furthermore, our investigation into the expression of PCRSMs unveiled a significant negative correlation between the expression of hsa-miR-125b-1-3p and age.

Conclusion

Our study introduces a novel artificial neural network model for early diagnosis of pancreatic cancer, carrying significant clinical implications. Furthermore, our findings provide valuable insights into the pathogenesis of pancreatic cancer and offer potential avenues for drug screening, personalized treatment, and immunotherapy against this lethal disease.
Distribution of transpulmonary pressure during one-lung ventilation in pigs at different body positions
Authors: Wittenstein Jakob , Scharffenberg Martin , Yang Xiuli , Bluth Thomas , Kiss Thomas , Schultz Marcus J. , Rocco Patricia R. M. , Pelosi Paolo , Gama de Abreu Marcelo , Huhle Robert
Published: August 2023

Background. Global and regional transpulmonary pressure (PL) during one-lung ventilation (OLV) is poorly characterized. We hypothesized that global and regional PL and driving PL (ΔPL) increase during protective low tidal volume OLV compared to two-lung ventilation (TLV), and vary with body position.

Methods. In sixteen anesthetized juvenile pigs, intra-pleural pressure sensors were placed in ventral, dorsal, and caudal zones of the left hemithorax by video-assisted thoracoscopy. A right thoracotomy was performed and lipopolysaccharide administered intravenously to mimic the inflammatory response due to thoracic surgery. Animals were ventilated in a volume-controlled mode with a tidal volume (VT) of 6 mL kg−1 during TLV and of 5 mL kg−1 during OLV and a positive end-expiratory pressure (PEEP) of 5 cmH2O. Global and local transpulmonary pressures were calculated. Lung instability was defined as end-expiratory PL<2.9 cmH2O according to previous investigations. Variables were acquired during TLV (TLVsupine), left lung ventilation in supine (OLVsupine), semilateral (OLVsemilateral), lateral (OLVlateral) and prone (OLVprone) positions randomized according to Latin-square sequence. Effects of position were tested using repeated measures ANOVA.

Results. End-expiratory PL and ΔPL were higher during OLVsupine than TLVsupine. During OLV, regional end-inspiratory PL and ΔPL did not differ significantly among body positions. Yet, end-expiratory PL was lower in semilateral (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and lateral (ventral: 1.9 ± 3.3 cmH2O; caudal: 2.7 ± 1.7 cmH2O) compared to supine (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and prone position (ventral: 1.7 ± 2.5 cmH2O; caudal: 3.3 ± 1.6 cmH2O), mainly in ventral (p ≤ 0.001) and caudal (p = 0.007) regions. Lung instability was detected more often in semilateral (26 out of 48 measurements; p = 0.012) and lateral (29 out of 48 measurements, p < 0.001) as compared to supine position (15 out of 48 measurements), and more often in lateral as compared to prone position (19 out of 48 measurements, p = 0.027).

Conclusion. Compared to TLV, OLV increased lung stress. Body position did not affect stress of the ventilated lung during OLV, but lung stability was lowest in semilateral and lateral decubitus position.