bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of cuproptosis-related lncRNAs associated with pancreatic cancer immune microenvironment based on single-cell
Authors: Sun Yimeng , Yao Lin , Man Changfeng , Gao Zhenjun , He Rong , Fan Yu
Published: September 2023

Background

Cuproptosis, a novel mode of cell death associated with the tricarboxylic acid (TCA) cycle, is relevant to the development of cancer. However, the impact of single-cell-based Cuproptosis-associated lncRNAs on the Tumor immune microenvironment (TIME) of Pancreatic adenocarcinoma (PAAD) and its potential value for individualized immunotherapy has not been clarified.

Methods

14 immune-related CRGs were screened by exploring the interaction between differentially expressed Immune-Related Genes (IRGs) and Cuproptosis-Related Genes (CRGs) in PAAD. Next, the expression amount and expression distribution of CRGs in single-cell samples were analyzed by focusing on 7-CRGs with significant expressions. On the one hand, MAP2K2, SOD1, and VEGFA, which were significantly differentially expressed between PAAD sites and normal tissues adjacent to them, were subjected to immunohistochemical validation and immune landscape analysis. On the other hand, from these 7-CRGs, prognostic signatures of lncRNAs were established by co-expression and LASSO-COX regression analysis, and their prognostic value and immune relevance were assessed. In addition, this study not only validated the hub CRGs and the lncRNAs constituting the signature in a PAAD animal model treated with immunotherapy-based combination therapy using immunohistochemistry and qRT-PCR but also explored the potential value of the combination of targeted, chemotherapy and immunotherapy.

Results

Based on the screening of 7-CRGs significantly expressed in a PAAD single-cell cohort and their co-expressed Cuproptosis-Related lncRNAs (CRIs), this study constructed a prognostic signature of 4-CRIs named CIR-score. A Nomogram integrating the CIR-score and clinical risk factors was constructed on this basis to predict the individualized survival of patients. Moreover, high and low-risk groups classified according to the median of signatures exhibited significant differences in clinical prognosis, immune landscape, bioenrichment, tumor burden, and drug sensitivity. And the immunohistochemical and qRT-PCR results of different mouse PAAD treatment strategies were consistent with the trend of inter-group variability in drug sensitivity of hub CRGs and CIR-score. The combination of immunotherapy, targeted therapy, and chemotherapy exhibited a better tumor suppression effect.

Conclusion

CIR-score, as a Cuproptosis-related TIME-specific prognostic signature based on PAAD single cells, not only predicts the prognosis and immune landscape of PAAD patients but also provides a new strategy for individualized immunotherapy-based combination therapy.
In-depth characterization of NK cell markers from CML patients who discontinued tyrosine kinase inhibitor therapy
Authors: Sanchez María Belén , Vasconcelos Cordoba Bianca , Pavlovsky Carolina , Moiraghi Beatriz , Varela Ana , Custidiano Rosario , Fernandez Isolda , Freitas María Josefina , Ventriglia María Verónica , Bendek Georgina , Mariano Romina , Mela Osorio María José , Pavlovsky Miguel Arturo , García de Labanca Ana , Foncuberta Cecilia , Giere Isabel , Vera Masiel , Juni Mariana , Mordoh José , Sanchez Avalos Julio Cesar , Levy Estrella Mariel , Bianchini Michele
Published: September 2023

Introduction

Treatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase is considered a safe option if suitable molecular monitoring is available. However, the question arises as to which factors can contribute to the maintenance of TFR, and immunologic surveillance of the remaining leukemic cells is believed to be one of them. Argentina Stop Trial is an open-label, single-arm, multicenter trial assessing TFR after tyrosine kinase inhibitors interruption, that after more than 4 years showed a successful TFR rate of 63%.

Methods

In this context, we set up an immunological study by flow cytometry in order to analyze specific NK cell subsets from peripheral blood patient samples both at the time of discontinuation as well as during the subsequent months.

Results

At the time of discontinuation, patients show a mature NK cell phenotype, probably associated to TKI treatment. However, 3 months after discontinuation, significant changes in several NK cell receptors occurred. Patients with a higher proportion of CD56dim NK and PD-1+ NK cells showed better chances of survival. More interestingly, non-relapsing patients also presented a subpopulation of NK cells with features associated with the expansion after cytomegalovirus infection (expression of CD57+NKG2C+), and higher proportion of NKp30 and NKp46 natural cytotoxicity receptors, which resulted in greater degranulation and associated with better survival (p<0.0001).

Discussion

This NK cell subset could have a protective role in patients who do not relapse, thus further characterization could be useful for patients in sustained deep molecular response.
Precision in treatment evaluation: importance of minimal clinically important differences (MCIDs) of outcome measures for autoimmune blistering diseases
Authors: Tseng Henry , Stone Corey , Murrell Dédée F.
Published: September 2023

Autoimmune blistering diseases (AIBDs) comprise a group of rare conditions marked by autoantibodies that specifically target intercellular adhesion molecules. Despite the progress made in comprehending the disease and the increasing number of treatment options available, there is still no definitive cure for AIBDs such as pemphigus, and it continues to have a devastating impact on those affected. The challenges in achieving new approved therapies for AIBDs are complex and multifaceted. One significant obstacle was the prior lack of validated and standardized outcome measures, which are crucial for ensuring precise comparisons between new and traditional therapies. This gap in knowledge has prompted the development of minimal clinically important differences (MCIDs), which enable efficient and reliable comparison of therapeutic outcomes between trials. MCID is defined as the minimum difference in an outcome measure that indicates a clinically significant improvement/deterioration in disease severity. Additionally, MCIDs provide a patient-centered approach to evaluating treatment efficacy, by considering whether patients experience a subjective improvement in their symptoms. Therefore, this literature review will examine the derivation and significance of MCIDs for various scoring systems in AIBDs.
Extracellular vesicles in hematological malignancies: EV-dence for reshaping the tumoral microenvironment
Authors: Van Morckhoven David , Dubois Nathan , Bron Dominique , Meuleman Nathalie , Lagneaux Laurence , Stamatopoulos Basile
Published: September 2023

Following their discovery at the end of the 20th century, extracellular vesicles (EVs) ranging from 50-1,000 nm have proven to be paramount in the progression of many cancers, including hematological malignancies. EVs are a heterogeneous group of cell-derived membranous structures that include small EVs (commonly called exosomes) and large EVs (microparticles). They have been demonstrated to participate in multiple physiological and pathological processes by allowing exchange of biological material (including among others proteins, DNA and RNA) between cells. They are therefore a crucial way of intercellular communication. In this context, malignant cells can release these extracellular vesicles that can influence their microenvironment, induce the formation of a tumorigenic niche, and prepare and establish distant niches facilitating metastasis by significantly impacting the phenotypes of surrounding cells and turning them toward supportive roles. In addition, EVs are also able to manipulate the immune response and to establish an immunosuppressive microenvironment. This in turn allows for ideal conditions for heightened chemoresistance and increased disease burden. Here, we review the latest findings and reports studying the effects and therapeutic potential of extracellular vesicles in various hematological malignancies. The study of extracellular vesicles remains in its infancy; however, rapid advances in the analysis of these vesicles in the context of disease allow us to envision prospects to improve the detection and treatment of hematological malignancies.
Bridging soil biogeochemistry and microbial communities (archaea and bacteria) in tropical seagrass meadows
Authors: Nóbrega Gabriel Nuto , de Andrade Pedro Avelino Maia , Queiroz Hermano Melo , Pereira Arthur Prudêncio de Araújo , Copertino Margareth da Silva , Gorman Daniel , Zhuang Wen , Song Jinming , Andreote Fernando Dini , Otero Xosé Luis , Ferreira Tiago Osório
Published: September 2023

Introduction

Seagrass meadows are among the most valuable ecosystems, providing numerous ecosystem services and functions. Despite its importance, there is a lack of knowledge about soil’s biogeochemical process variability, which can control microbiological communities. Thus, this study aimed to evaluate whether seagrass meadows in different geo-environments exhibit varying Fe and sulfate reduction intensities, shaping distinct archaea and bacteria communities.

Methods

Soil samples were collected in seagrass meadows under contrasting climatic, geological, vegetational and hydrological settings along the Brazilian coast (e.g., Semiarid Coast - SC, Southeastern Granitic Coast – GC, and Southern Quaternary Coast - QC). The soils were characterized by particle size, pH, redox potential (Eh), total organic C and total N content, acid-volatile sulfides (AVS), and simultaneously extracted Fe. Furthermore, a solid-phase Fe fractionation was performed to characterize the decomposition pathways in these soils, and the shifts in the microbial community along this spatial variation were analyzed using denaturing gradient gel electrophoresis.

Results

The studied soils presented a sandy texture (values ranging from 74 ± 11.8 to 80.5 ± 6.4%) caused by energetic hydrodynamic conditions. The pH values were circumneutral, while redox conditions presented significant distinction among the studied sites, ranging from anoxic to oxic (values ranging from -63 to +334 mV). The degree of pyritization (DOP) ranged from< 10% to values higher than 80%, highly influenced by rhizospheric oxidation, and higher AVS content was recorded for sites with lower DOP (i.e., GC and QC).

Discussions

Thus, biogeochemical processes in the seagrass soils present a wide variation in response to the geo-environmental settings. Plants influence the soil’s geochemical and microbiological communities, retaining fine particles, promoting rhizosphere oxidation, and inducing anoxic conditions controlling the Fe and S forms. Moreover, the same plant species can result in distinct soil conditions and microbial communities due to geoenvironmental settings.
Assessment of the current status and effectiveness of area-based conservation measures banning trawling activities in the Adriatic Sea
Authors: Ferrà Carmen , Scarcella Giuseppe
Published: September 2023

The marine environment is highly stressed by anthropogenic pressures, among which fisheries, and in particular bottom trawling, are one of the main sources of impact. Area-based conservation measures can help conserve and restore ecosystems and population structures and therefore constitute a key tool to the achievement of the 14th Sustainable Development Goal, preservation of the ocean. The purpose of this paper is to provide an assessment of the compliance of area-based conservation measures. The Adriatic Sea has been selected as a case study area, as one of the most intensively trawled areas in the world where different countries share its resources and consequently different management strategies are put in place. We present a review of the marine managed areas established in the Adriatic Sea in 2019, providing information on their characteristics, temporal variabilities, and scopes. Through the processing of Automatic Identification System (AIS) data, the monthly bottom fishing activity performed within each area was inferred and the intensity was assessed. Thus, the effectiveness of trawling bans was evaluated. We demonstrated that full respect of the prohibition was effective in 73% of the areas, while trawling activity was recorded with different intensities in 149 out of 549 managed areas.
Diagnostic accuracy of perfusion-weighted phase-resolved functional lung magnetic resonance imaging in patients with chronic pulmonary embolism
Authors: Duan Jianghui , Xie Sheng , Sun Hongliang , An Jing , Li Huan , Li Ling , Grimm Robert , Voskrebenzev Andreas , Vogel-Claussen Jens
Published: September 2023

Purpose

This study aimed to evaluate the diagnostic performance of perfusion-weighted phase-resolved functional lung (PW-PREFUL) magnetic resonance imaging (MRI) in patients with chronic pulmonary embolism (CPE).

Materials and methods

This study included 86 patients with suspected chronic thromboembolic pulmonary hypertension (CTEPH), who underwent PREFUL MRI and ventilation/perfusion (V/Q) single-photon emission computed tomography/computed tomography (SPECT/CT). PREFUL MRI was performed at 1.5 T using a balanced steady-state free precession sequence during free breathing. Color-coded PW images and quantitative parameters were obtained by postprocessing. Meanwhile, V/Q SPECT/CT imaging was performed as a reference standard. Hypoperfused areas in the lungs were scored for each lobe and segment using V/Q SPECT/CT images and PW-PREFUL MR images, respectively. Normalized perfusion (QN) and perfusion defect percentage (QDP) were calculated for all slices. For intra- and interobserver variability, the MRI images were analyzed 2 months after the first analysis by the same radiologist and another radiologist (11 years of lung MRI experience) blinded to the results of the first reader.

Results

Of the 86 enrolled patients, 77 met the inclusion criteria (36 diagnosed with CPE using V/Q SPECT/CT and 41 diagnosed with non-CPE etiology). For the PW-PREFUL MRI, the sensitivity, specificity, accuracy, and positive and negative predictive values for the diagnosis of CPE were 97, 95, 96, 95, and 98% at the patient level; 91, 94, 93, 91, and 94% at the lobe level, and 85, 94, 92, 88, and 94% at the segment level, respectively. The detection of segmental and subsegmental hypoperfusion using PW-PREFUL MRI revealed a moderate agreement with V/Q SPECT/CT (κ = 0.65; 95% confidence interval: 0.61–0.68). The quantitative results indicated that the QN was lower in the CPE group than in the non-CPE group [median score (interquartile range, IQR) 6.3 (2.8–9.2) vs. 13.0 (8.8–16.7), p < 0.001], and the QDP was higher [median score (IQR) 33.8 (15.7–51.7) vs. 2.2 (1.4–2.9), p < 0.001].

Conclusion

PREFUL MRI could be an alternative test to detect CPE without requiring breath-hold, contrast agents, or ionizing radiation.
Role of Legionella pneumophila outer membrane vesicles in host-pathogen interaction
Authors: Ayesha Ayesha , Chow Franklin Wang-Ngai , Leung Polly Hang-Mei
Published: September 2023

Legionella pneumophila is an opportunistic intracellular pathogen that inhabits artificial water systems and can be transmitted to human hosts by contaminated aerosols. Upon inhalation, it colonizes and grows inside the alveolar macrophages and causes Legionnaires’ disease. To effectively control and manage Legionnaires’ disease, a deep understanding of the host-pathogen interaction is crucial. Bacterial extracellular vesicles, particularly outer membrane vesicles (OMVs) have emerged as mediators of intercellular communication between bacteria and host cells. These OMVs carry a diverse cargo, including proteins, toxins, virulence factors, and nucleic acids. OMVs play a pivotal role in disease pathogenesis by helping bacteria in colonization, delivering virulence factors into host cells, and modulating host immune responses. This review highlights the role of OMVs in the context of host-pathogen interaction shedding light on the pathogenesis of L. pneumophila. Understanding the functions of OMVs and their cargo provides valuable insights into potential therapeutic targets and interventions for combating Legionnaires’ disease.
Differential features of early childhood motor skill development and working memory processing: evidence from fNIRS
Authors: Zheng Quanliang , Chi Aiping , Shi Bing , Wang Yimin , Ma Qing , Zhou Fang , Guo Xianmei , Zhou Menghan , Lin Bowei , Ning Ke
Published: September 2023

Objective

The study investigated the differential characteristics associated with motor skill development and working memory processing during early childhood, thereby providing insights for understanding motor learning and cognitive development in young children.

Methods

In total, 101 preschool children (age: 4–6 years) were recruited for this study. The motor skill development level and the working memory capacity of the children were assessed using the MOBAK Motor Development Assessment Scale and a block task paradigm, respectively. Functional near-infrared spectroscopy brain imaging technology was used to monitor hemodynamic signals in the prefrontal cortex (PFC) of the children while they completed different memory tasks. MATLAB software and the Homer2 plugin were used to calculate the oxygenated hemoglobin (Oxy-Hb) concentration in relevant brain regions during the tasks.

Results

(1) The low motor skill group exhibited significantly lower accuracy during the three-memory load condition than during the two-memory load condition. Under both two-memory and three-memory load conditions, the high motor skill group exhibited significantly higher accuracy than the low motor skill group. (2) Significant differences in the Oxy-Hb concentration were observed in the left dorsolateral PFC (L-DLPFC), and right and left triangular part of the Broca’s area (R-PTBA and L-PTBA, respectively) between the two memory difficulty levels for the high motor skill group. The Oxy-Hb concentration was significantly higher during the three-memory load condition than during the two-memory load condition. Under the two-memory load condition, the high motor skill group exhibited significantly higher Oxy-Hb concentration in the L-DLPFC and L-PTBA regions than in the low motor skill group. Under the three-memory load condition, the high motor skill group exhibited significantly higher Oxy-Hb concentration in the L-DLPFC, R-PTBA, and L-PTBA regions than the low motor skill group.

Conclusion

A close association was observed between the motor skill levels and working memory in young children, with higher motor skill levels being associated with more pronounced brain activation patterns during working memory tasks.
Orally administered low-molecular weight agaro-oligosaccharides are absorbed into the plasma of healthy humans
Authors: Shirai Ikuya , Iwasaki Yu , Karasawa Koji , Shigemura Yasutaka , Katayama Shigeru
Published: September 2023

Agaro-oligosaccharides (AOSs) are known to have biological activities, such as anti-inflammatory, anti-tumor, and anti-obesity effects. Although existing evidence suggests the presence of AOSs in peripheral tissues after oral administration, whether AOSs permeate into the blood circulation remains unknown. Thus, we hypothesized that AOSs with low-molecular weight can permeate the human gastrointestinal tract. To test this hypothesis, the time course of absorption was examined by analyzing plasma samples before and 1, 2, and 4 h after ingestion. Analysis was performed using liquid chromatography/mass spectrometry after labeling with p-aminobenzoic ethyl ester. Our results showed that the plasma concentration of agarobiose (Abi) was higher than that of agarotetraose (Ate); however, agarohexaose was not detected. Additionally, plasma levels of Abi and Ate were proportional to the dose. These results suggest that permeation efficiency is dependent on the molecular weight and that the systemic absorption of Abi via the gastrointestinal tract is better than that of Ate. These findings will contribute to a better understanding of the bioactivity of orally administered AOSs in peripheral tissues.
Revolutionizing anti-cancer drug discovery against breast cancer and lung cancer by modification of natural genistein: an advanced computational and drug design approach
Authors: Akash Shopnil , Bibi Shabana , Biswas Partha , Mukerjee Nobendu , Khan Dhrubo Ahmed , Hasan Md. Nazmul , Sultana Nazneen Ahmeda , Hosen Md. Eram , Jardan Yousef A. Bin , Nafidi Hiba-Allah , Bourhia Mohammed
Published: September 2023

Breast and lung cancer are two of the most lethal forms of cancer, responsible for a disproportionately high number of deaths worldwide. Both doctors and cancer patients express alarm about the rising incidence of the disease globally. Although targeted treatment has achieved enormous advancements, it is not without its drawbacks. Numerous medicines and chemotherapeutic drugs have been authorized by the FDA; nevertheless, they can be quite costly and often fall short of completely curing the condition. Therefore, this investigation has been conducted to identify a potential medication against breast and lung cancer through structural modification of genistein. Genistein is the active compound in Glycyrrhiza glabra (licorice), and it exhibits solid anticancer efficiency against various cancers, including breast cancer, lung cancer, and brain cancer. Hence, the design of its analogs with the interchange of five functional groups—COOH, NH2 and OCH3, Benzene, and NH-CH2-CH2-OH—have been employed to enhance affinities compared to primary genistein. Additionally, advanced computational studies such as PASS prediction, molecular docking, ADMET, and molecular dynamics simulation were conducted. Firstly, the PASS prediction spectrum was analyzed, revealing that the designed genistein analogs exhibit improved antineoplastic activity. In the prediction data, breast and lung cancer were selected as primary targets. Subsequently, other computational investigations were gradually conducted. The mentioned compounds have shown acceptable results for in silico ADME, AMES toxicity, and hepatotoxicity estimations, which are fundamental for their oral medication. It is noteworthy that the initial binding affinity was only −8.7 kcal/mol against the breast cancer targeted protein (PDB ID: 3HB5). However, after the modification of the functional group, when calculating the binding affinities, it becomes apparent that the binding affinities increase gradually, reaching a maximum of −11.0 and −10.0 kcal/mol. Similarly, the initial binding affinity was only −8.0 kcal/mol against lung cancer (PDB ID: 2P85), but after the addition of binding affinity, it reached −9.5 kcal/mol. Finally, a molecular dynamics simulation was conducted to study the molecular models over 100 ns and examine the stability of the docked complexes. The results indicate that the selected complexes remain highly stable throughout the 100-ns molecular dynamics simulation runs, displaying strong correlations with the binding of targeted ligands within the active site of the selected protein. It is important to further investigate and proceed to clinical or wet lab experiments to determine the practical value of the proposed compounds.
Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model
Authors: McLean Dalton T. , Meudt Jennifer J. , Lopez Rivera Loren D. , Schomberg Dominic T. , Pavelec Derek M. , Duellman Tyler T. , Buehler Darya G. , Schwartz Patrick B. , Graham Melissa , Lee Laura M. , Graff Keri D. , Reichert Jamie L. , Bon-Durant Sandra S. , Konsitzke Charles M. , Ronnekleiv-Kelly Sean M. , Shanmuganayagam Dhanansayan , Rubinstein C. Dustin
Published: September 2023

Neurofibromatosis Type 1 (NF1) is one of the most common genetically inherited disorders that affects 1 in 3000 children annually. Clinical manifestations vary widely but nearly always include the development of cutaneous, plexiform and diffuse neurofibromas that are managed over many years. Recent single-cell transcriptomics profiling efforts of neurofibromas have begun to reveal cell signaling processes. However, the cell signaling networks in mature, non-cutaneous neurofibromas remain unexplored. Here, we present insights into the cellular composition and signaling within mature neurofibromas, contrasting with normal adjacent tissue, in a porcine model of NF1 using single-cell RNA sequencing (scRNA-seq) analysis and histopathological characterization. These neurofibromas exhibited classic diffuse-type histologic morphology and expected patterns of S100, SOX10, GFAP, and CD34 immunohistochemistry. The porcine mature neurofibromas closely resemble human neurofibromas histologically and contain all known cellular components of their human counterparts. The scRNA-seq confirmed the presence of all expected cell types within these neurofibromas and identified novel populations of fibroblasts and immune cells, which may contribute to the tumor microenvironment by suppressing inflammation, promoting M2 macrophage polarization, increasing fibrosis, and driving the proliferation of Schwann cells. Notably, we identified tumor-associated IDO1+/CD274+ (PD-L1)+ dendritic cells, which represent the first such observation in any NF1 animal model and suggest the role of the upregulation of immune checkpoints in mature neurofibromas. Finally, we observed that cell types in the tumor microenvironment are poised to promote immune evasion, extracellular matrix reconstruction, and nerve regeneration.
Morphological features of the photoplethysmographic signal: a new approach to characterize the microcirculatory response to photobiomodulation
Authors: Ovadia-Blechman Zehava , Hauptman Yermiyahu , Rabin Neta , Wiezman Gal , Hoffer Oshrit , Gertz S. David , Gavish Benjamin , Gavish Lilach
Published: September 2023

Introduction and Objectives: Advanced analysis of the morphological features of the photoplethysmographic (PPG) waveform may provide greater understanding of mechanisms of action of photobiomodulation (PBM). Photobiomodulation is a non-ionizing, red to near-infrared irradiation shown to induce peripheral vasodilatation, promote wound healing, and reduce pain. Using laser Doppler flowmetry combined with thermal imaging we found previously in a clinical study that PBM stimulates microcirculatory blood flow and that baseline palm skin temperature determines, at least in part, why some individuals respond favorably to PBM while others do not. “Responders” (n = 12) had a skin temperature range of 33°C–37.5°C, while “non-responders” (n = 8) had “cold” or “hot” skin temperature (<33°C or >37.5°C respectively). The continuous PPG signals recorded from the index fingers of both hands in the original clinical study were subjected to advanced post-acquisitional analysis in the current study, aiming to identify morphological features that may improve the accuracy of discrimination between potential responders and non-responders to PBM.

Methods: The PPG signals were detrended by subtracting the lower envelope from the raw signal. The Root Mean Square (RMS) and Entropy features were extracted as were two additional morphological features -- Smoothness and number of local extrema per PPG beat (#Extrema). These describe the signal jaggedness and were developed specifically for this study. The Wilcoxon test was used for paired comparisons. Correlations were determined by the Spearman correlation test (rs).

Results: The PPG waveforms of responders to PBM had increased amplitude and decreased jaggedness (Baseline vs. 10’ post-irradiation: Entropy, 5.0 ± 1.3 vs. 3.9 ± 1.1, p = 0.012; #Extrema, 4.0 ± 1.1 vs. 3.0 ± 1.6, p = 0.009; RMS, 1.6 ± 0.9 vs. 2.3 ± 1.2, p = 0.004; Smoothness, 0.10 ± 0.05 vs. 0.19 ± 0.16, p = 0.016). In addition, unilateral irradiation resulted in a bilateral response, although the response of the contralateral, non-irradiated hand was shorter in duration and lower in magnitude. Although subjects with ‘cold,’ or ‘hot,’ baseline skin temperature appeared to have morphologically distinct PPG waveforms, representing vasoconstriction and vasodilatation, these were not affected by PBM irradiation.

Conclusion: This pilot study indicates that post-acquisitional analysis of morphological features of the PPG waveform provides new measures for the exploration of microcirculation responsiveness to PBM.
2-NBDG Uptake in Gossypium hirsutum in vitro ovules: exploring tissue-specific accumulation and its impact on hexokinase-mediated glycolysis regulation
Authors: Shamshoum Melina , Kuperman Ofir Aharon , Shadmi Sapir Korman , Itkin Maxim , Malitsky Sergey , Natalio Filipe
Published: September 2023

Fluorescent glucose derivatives are valuable tools as glucose analogs in plant research to explore metabolic pathways, study enzyme activity, and investigate cellular processes related to glucose metabolism and sugar transport. They allow visualization and tracking of glucose uptake, its utilization, and distribution within plant cells and tissues. This study investigates the phenotypic and metabolic impact of the exogenously fed glucose derivative, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose) (2-NBDG) on the fibers of Gossypium hirsutum (Upland cotton) ovule in vitro cultures. The presence of 2-NBDG in the culture medium did not lead to macroscopic morphological alterations in ovule and fiber development or to the acquisition of fluorescence or yellow coloration. Confocal laser scanning microscope imaging and chromatographic analysis of cotton ovules’ outer rim cross-sections showed that the 2-NBDG is transported from the extracellular space and accumulated inside some outer integument cells, epidermal cells, and fertilized epidermal cells (fibers), but is not incorporated into the cell walls. Untargeted metabolic profiling of the fibers revealed significant changes in the relative levels of metabolites involved in glycolysis and upregulation of alternative energy-related pathways. To provide biochemical and structural evidence for the observed downregulation of glycolysis pathways in the fibers containing 2-NBDG, kinetics analysis and docking simulations were performed on hexokinase from G. hirsutum (GhHxk). Notably, the catalytic activity of heterologously expressed recombinant active GhHxk exhibited a five-fold decrease in reaction rates compared to D-glucose. Furthermore, GhHxk exhibited a linear kinetic behavior in the presence of 2-NBDG instead of the Michaelis-Menten kinetics found for D-glucose. Docking simulations suggested that 2-NBDG interacts with a distinct binding site of GhHxk9, possibly inducing a conformational change. These results highlight the importance of considering fluorescent glucose derivatives as ready-to-use analogs for tracking glucose-related biological processes. However, a direct comparison between their mode of action and its extrapolation into biochemical considerations should go beyond microscopic inspection and include complementary analytical techniques.
Genomic selection to improve husk tightness based on genomic molecular markers in maize
Authors: Liu Yuncan , Ao Man , Lu Ming , Zheng Shubo , Zhu Fangbo , Ruan Yanye , Guan Yixin , Zhang Ao , Cui Zhenhai
Published: September 2023

Introduction

The husk tightness (HTI) in maize plays a crucial role in regulating the water content of ears during the maturity stage, thereby influencing the quality of mechanical grain harvesting in China. Genomic selection (GS), which employs molecular markers, offers a promising approach for identifying and selecting inbred lines with the desired HTI trait in maize breeding. However, the effectiveness of GS is contingent upon various factors, including the genetic architecture of breeding populations, sequencing platforms, and statistical models.

Methods

An association panel of maize inbred lines was grown across three sites over two years, divided into four subgroups. GS analysis for HTI prediction was performed using marker data from three sequencing platforms and six marker densities with six statistical methods.

Results

The findings indicate that a loosely attached husk can aid in the dissipation of water from kernels in temperate maize germplasms across most environments but not nessarily for tropical-origin maize. Considering the balance between GS prediction accuracy and breeding cost, the optimal prediction strategy is the rrBLUP model, the 50K sequencing platform, a 30% proportion of the test population, and a marker density of r2=0.1. Additionally, selecting a specific SS subgroup for sampling the testing set significantly enhances the predictive capacity for husk tightness.

Discussion

The determination of the optimal GS prediction strategy for HTI provides an economically feasible reference for the practice of molecular breeding. It also serves as a reference method for GS breeding of other agronomic traits.
Ecosystem multifunctionality, maximum height, and biodiversity of shrub communities affected by precipitation fluctuations in Northwest China
Authors: Du Lan , Tian Shengchuan , Sun Jing , Zhang Bin , Mu Xiao-Han , Tang Lisong , Zheng Xinjun , Li Yan
Published: September 2023

Introduction

Dryland ecosystems face serious threats from climate change. Establishing the spatial pattern of ecosystem multifunctionality, maximum height and the correlation of biodiversity patterns with climate change is important for understanding changes in complex ecosystem processes. However, the understanding of their relationships across large spatial areas remains limited in drylands.

Methods

Accordingly, this study examined the spatial patterns of ecosystem multifunctionality, maximum height and considered a set of potential environmental drivers by investigating natural shrub communities in Northwest China.

Results

We found that the ecosystem multifunctionality (EMF) and maximum height of shrub communities were both affected by longitude, which was positively correlated with the precipitation gradient. Specifically, the EMF was driven by high precipitation seasonality, and the maximum height was driven by high precipitation stability during the growing season. Among the multiple biodiversity predictors, species beta diversity (SD-beta) is the most common in determining EMF, although this relationship is weak.

Discussion

Unlike tree life form, we did not observe biodiversity-maximum height relationships in shrub communities. Based on these results, we suggest that more attention should be paid to the climatical fluctuations mediated biodiversity mechanisms, which are tightly correlated with ecosystem’s service capacity and resistance capacity under a rapid climate change scenario in the future.
High executive functioning is associated with reduced posttraumatic stress after trauma exposure among male U.S. military personnel
Authors: Liu Sabrina R. , Moore Tyler M. , Gur Ruben C. , Nievergelt Caroline , Baker Dewleen G. , Risbrough Victoria , Acheson Dean T.
Published: September 2023

Introduction

Evidence suggests that executive function (EF) may play a key role in development of PTSD, possibly influenced by factors such as trauma type and timing. Since EF can be improved through intervention, it may be an important target for promoting resilience to trauma exposure. However, more research is needed to understand the relation between trauma exposure, EF, and PTSD. The goal of this study was to improve understanding of EF as a potential antecedent or protective factor for the development of PTSD among military personnel.

Method

In a cohort of U.S. Marines and Navy personnel (N = 1,373), the current study tested the association between exposure to traumatic events (pre-deployment and during deployment) and PTSD severity, and whether EF moderated these associations. Three types of pre-deployment trauma exposure were examined: cumulative exposure, which included total number of events participants endorsed as having happened to them, witnessed, or learned about; direct exposure, which included total number of events participants endorsed as having happened to them; and interpersonal exposure, which included total number of interpersonally traumatic events participants’ endorsed. EF was measured using the Penn Computerized Neurocognitive Battery.

Results

EF was associated with less PTSD symptom severity at pre-deployment, even when adjusting for trauma exposure, alcohol use, traumatic brain injury, and number of years in the military. EF also moderated the relation between cumulative trauma exposure and interpersonal trauma exposure and PTSD, with higher EF linked to a 20 and 33% reduction in expected point increase in PTSD symptoms with cumulative and interpersonal trauma exposure, respectively. Finally, higher pre-deployment EF was associated with reduced PTSD symptom severity at post-deployment, independent of deployment-related trauma exposure and adjusting for pre-deployment PTSD.

Conclusion

Our results suggest that EF plays a significant, if small role in the development of PTSD symptoms after trauma exposure among military personnel. These findings provide important considerations for future research and intervention and prevention, specifically, incorporating a focus on improving EF in PTSD treatment.
Perception and willingness toward various immunization routes for COVID-19 vaccines: a cross-sectional survey in China
Authors: Wang Haohang , Cui Mingting , Li Shunran , Wu Fan , Jiang Shiqiang , Chen Hongbiao , Yuan Jianhui , Sun Caijun
Published: September 2023

Background

To date, most vaccines, including the COVID-19 vaccine, are mainly administered by intramuscular injection, which might lead to vaccine hesitancy in some populations due to needle fear. Alternatively, needle-free immunization technology is extensively developed to improve the efficacy and acceptance of vaccination. However, there is no study to report the perception and willingness toward various immunization routes of the COVID-19 vaccine in the general population.

Methods

A cross-sectional survey was conducted nationwide using an online questionnaire. Bivariate analyses were undertaken to assess variable associations among the participants who reported a hesitancy to receive the COVID-19 booster vaccination. Multivariable logistic regression with a backward step-wise approach was used to analyze the predicted factors associated with the willingness to receive the COVID-19 booster vaccination.

Results

A total of 3,244 valid respondents were included in this survey, and 63.2% of participants thought they had a good understanding of intramuscular injection, but only 20.7, 9.2, 9.4, and 6.0% of participants had a self-perceived good understanding of inhalation vaccine, nasal spray vaccine, oral vaccine, and microneedle patch vaccine. Correspondingly, there was high acceptance for intramuscular injection (76.5%), followed by oral inhalation (64.4%) and nasal spray (43.0%). Those participants who were only willing to receive an intramuscular vaccine had less vaccine knowledge (OR = 0.78; 95% CI: 0.65–0.94) than those who were willing to receive a needle-free vaccine (OR = 1.97; 95% CI: 1.52–2.57). Some factors were found to be associated with vaccine hesitancy toward booster COVID-19 vaccination.

Conclusion

Needle-free vaccination is a promising technology for the next generation of vaccines, but we found that intramuscular injection was still the most acceptable immunization route in this survey. One major reason might be that most people lack knowledge about needle-free vaccination. We should strengthen the publicity of needle-free vaccination technology, and thus improve the acceptance and coverage of vaccination in different populations.
Psychological assessment of AI-based decision support systems: tool development and expected benefits
Authors: Buschmeyer Katharina , Hatfield Sarah , Zenner Julie
Published: September 2023

This study aimed to develop an evaluation tool that assesses the use of AI-based decision support systems (DSSs) in professional practice from a human-centered perspective. Following the International Organization for Standardization, this perspective aims to ensure that the use of interactive technologies improves users' psychological load experience and behavior, e.g., in the form of reduced stress experience or increased performance. Concomitantly, this perspective attempts to proactively prevent or detect and correct the potential negative effects of these technologies on user load, such as impaired satisfaction and engagement, as early as possible. Based on this perspective, we developed and validated a questionnaire instrument, the Psychological Assessment of AI-based DSSs (PAAI), for the user-centered evaluation of the use of AI-based DSSs in practice. In particular, the instrument considers central design characteristics of AI-based DSSs and the corresponding work situation, which have a significant impact on users' psychological load. The instrument was tested in two independent studies. In Study 1, N = 223 individuals were recruited. Based on the results of item and scale analyses and an exploratory factor analysis, the newly developed instrument was refined, and the final version was tested using a confirmatory factor analysis. Findings showed acceptable-to-good fit indices, confirming the factorial validity of the PAAI. This was confirmed in a second study, which had N = 471 participants. Again, the CFA yielded acceptable-to-good fit indices. The validity was further confirmed using convergent and criterion validity analyses.
Integrating geographic data and the SCS-CN method with LSTM networks for enhanced runoff forecasting in a complex mountain basin
Authors: Merizalde María José , Muñoz Paul , Corzo Gerald , Muñoz David F. , Samaniego Esteban , Célleri Rolando
Published: September 2023

Introduction

In complex mountain basins, hydrological forecasting poses a formidable challenge due to the intricacies of runoff generation processes and the limitations of available data. This study explores the enhancement of short-term runoff forecasting models through the utilization of long short-term memory (LSTM) networks.

Methods

To achieve this, we employed feature engineering (FE) strategies, focusing on geographic data and the Soil Conservation Service Curve Number (SCS-CN) method. Our investigation was conducted in a 3,390 km2 basin, employing the GSMaP-NRT satellite precipitation product (SPP) to develop forecasting models with lead times of 1, 6, and 11 h. These lead times were selected to address the needs of near-real-time forecasting, flash flood prediction, and basin concentration time assessment, respectively.

Results and discussion

Our findings demonstrate an improvement in the efficiency of LSTM forecasting models across all lead times, as indicated by Nash-Sutcliffe efficiency values of 0.93 (1 h), 0.77 (6 h), and 0.67 (11 h). Notably, these results are on par with studies relying on ground-based precipitation data. This methodology not only showcases the potential for advanced data-driven runoff models but also underscores the importance of incorporating available geographic information into precipitation-ungauged hydrological systems. The insights derived from this study offer valuable tools for hydrologists and researchers seeking to enhance the accuracy of hydrological forecasting in complex mountain basins.
Concordance analysis of cerebrospinal fluid with the tumor tissue for integrated diagnosis in gliomas based on next-generation sequencing
Authors: Wang Qiang , Liang Qiujin , Wei Wuting , Niu Wenhao , Liang Chong , Wang Xiaoliang , Wang Xiaoxuan , Pan Hao
Published: September 2023

Purpose: The driver mutations of gliomas have been identified in cerebrospinal fluid (CSF). Here we compared the concordance between CSF and tumor tissue for integrated diagnosis in gliomas using next-generation sequencing (NGS) to evaluate the feasibility of CSF detection in gliomas.

Patients and methods: 27 paired CSF/tumor tissues of glioma patients were sequenced by a customized gene panel based on NGS. All CSF samples were collected through lumbar puncture before surgery. Integrated diagnosis was made by analysis of histology and tumor DNA molecular pathology according to the 2021 WHO classification of the central nervous system tumors.

Results: A total of 24 patients had detectable circulating tumor DNA (ctDNA) and 22 had at least one somatic mutation or chromosome alteration in CSF. The ctDNA levels varied significantly across different ages, Ki-67 index, magnetic resonance imaging signal and glioma subtypes (p < 0.05). The concordance between integrated ctDNA diagnosis and the final diagnosis came up to 91.6% (Kappa, 0.800). We reclassified the clinical diagnosis of 3 patients based on the results of CSF ctDNA sequencing, and 4 patients were reassessed depending on tumor DNA. Interestingly, a rare IDH1 R132C was identified in CSF ctDNA, but not in the corresponding tumor sample.

Conclusion: This study demonstrates a high concordance between integrated ctDNA diagnosis and the final diagnosis of gliomas, highlighting the practicability of NGS based detection of mutations of CSF in assisting integrated diagnosis of gliomas, especially glioblastoma.
Design and Experiment of a Multi-DOF Shaker Based on Rotationally Symmetric Stewart Platforms with an Insensitive Condition Number
Authors: Liang Chao , Li Weipeng , Huang Hai , Zheng Yan
Published: September 2023

This study proposes a method for designing a class of rotationally symmetric Stewart platforms (RSSPs) with an insensitive condition number (ICN), which is used to minimize the condition number to achieve a high accuracy for a multi-degree-of-freedom (multi-DOF) shaker. Considering the rotational symmetry of RSSPs, an analytical relationship between the architecture parameters and transfer coefficients is first established. Then, the decoupling conditions of the RSSPs are derived, and the transfer coefficient formulas are simplified by the given decoupling conditions and iso-length assumption. Following further analyses and discussions, the ICN condition and analytical form of the condition number are provided. The area of the ICN (AICN) is, subsequently, derived to evaluate the insensitivity of the condition number. To validate the effectiveness of the method, a design example (ICN-RSSP), along with a numerical analysis, is implemented, and, finally, a multi-DOF shaker is developed. The results of the numerical analysis show a smaller condition number and a larger AICN than those of the RSSP, for comparison. And the experiment results of the multi-DOF shaker show a high accuracy of vibration waveform reproduction. The method can reduce the condition number of RSSPs, improve the insensitivity, and further improve the accuracy of the multi-DOF shaker.
Selection of Design Scheme for an Ultrahigh-Pressure Hydrostatic Extrusion Cylinder
Authors: Yang Jian , Zhang Lei , Zhang Jun , Wang Hao , Zhang Dong , Luo Yuanxin , Wang Yongqin
Published: September 2023

In this study, the mechanical models of a multilayer combined extrusion cylinder and a steel-wire-winding extrusion cylinder were established and compared using a finite element simulation and existing experimental cases. This work provides theoretical support for the selection of an ultrahigh-pressure extrusion cylinder. Comparative analysis of an ultrahigh-pressure extrusion structure was carried out. The mathematical optimization model is established based on the mechanical model, and the ultimate bearing capacities of the schemes are compared. Additionally, the winding mode and the number of core layers of the extrusion cylinder are compared and analyzed, which provides a theoretical basis for the parameter design of the steel-wire-winding ultrahigh-pressure extrusion cylinder. This work holds good theoretical significance and practical value for the promotion and application of ultrahigh-pressure hydrostatic extrusion technology.