bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell RNA sequencing reveals distinct tumor microenvironment of ground glass nodules and solid nodules in lung adenocarcinoma
Authors: Huang Xiaofeng , Lu Zhimeng , Jiang Xuewei , Zhang Zhe , Yan Kun , Yu Guiping
Published: September 2023

Introduction: Lung adenocarcinoma (LUAD) is the most prevalent lung cancer. LUAD presents as ground glass nodules (GGN) and solid nodules (SN) in imaging studies. GGN is an early type of LUAD with good prognosis. However, SN exhibits a more malignant behavior than GGN, including worse pathological staging and tumor prognosis. The mechanism leading to the different malignancy levels of GGN and SN remains elusive.

Methods: Three patients with GGN and three patients with SN diagnosed with early LUAD were enrolled. The tumor samples were digested to a single-cell suspension and analyzed using 10× Genomic Single-cell ribonucleic acid sequences (scRNA-seq) techniques.

Results: A total of 15,902 cells were obtained and classified into nine major types. The tumor microenvironment (TME) was subsequently described in detail. ScRNA-seq revealed that ribosome-related pathways and cell adhesion played similar but distinct roles in the two groups. SN also had more active cell proliferation, enriched cell cycle regulatory pathways, and severe inflammatory responses.

Conclusion: We observed changes in the cellular composition and transcriptomic profile of GGN and SN. The study improved the understanding of the underlying mechanisms of lung carcinogenesis and contributed to lung cancer prevention and treatment.
A comparative analysis of gene and protein expression in chronic and acute models of photoreceptor degeneration in adult zebrafish
Authors: Kramer Ashley C. , Carthage Justin , Berry Yasmeen , Gurdziel Katherine , Cook Tiffany A. , Thummel Ryan
Published: September 2023

Background: Adult zebrafish are capable of photoreceptor (PR) regeneration following acute phototoxic lesion (AL). We developed a chronic low light (CLL) exposure model that more accurately reflects chronic PR degeneration observed in many human retinal diseases.

Methods: Here, we characterize the morphological and transcriptomic changes associated with acute and chronic models of PR degeneration at 8 time-points over a 28-day window using immunohistochemistry and 3′mRNA-seq.

Results: We first observed a differential sensitivity of rod and cone PRs to CLL. Next, we found no evidence for Müller glia (MG) gliosis or regenerative cell-cycle re-entry in the CLL model, which is in contrast to the robust gliosis and proliferative response from resident MG in the AL model. Differential responses of microglia between the models was also observed. Transcriptomic comparisons between the models revealed gene-specific networks of PR regeneration and degeneration, including genes that are activated under conditions of chronic PR stress. Finally, we showed that CLL is at least partially reversible, allowing for rod and cone outer segment outgrowth and replacement of rod cell nuclei via an apparent upregulation of the existing rod neurogenesis mechanism.

Discussion: Collectively, these data provide a direct comparison of the morphological and transcriptomic PR degeneration and regeneration models in zebrafish.
Determination of chemical constituent yields in e-cigarette aerosol using partial and whole pod collections, a comparative analysis
Authors: Jameson J. Brian , Wang Jiaming , Bailey Patrick C. , Oldham Michael J. , Smith Cameron R. , Jeong Lena N. , Cook David K. , Bates Austin L. , Ullah Sifat , Pennington Alexander S. C. , Gillman I. Gene
Published: September 2023

Literature reports the chemical constituent yields of electronic nicotine delivery systems (ENDS) aerosol collected using a range of aerosol collection strategies. The number of puffs to deplete an ENDS product varies widely, but collections often consist of data from the first 50–100 puffs. However, it is not clear whether these discrete puff blocks are representative of constituent yields over the life of a pod. We aimed to assess the effect of differing aerosol collection strategies on reported yields for select chemical constituents in the aerosol of closed pod-based ENDS products. Constituents analyzed were chosen to reflect important classes of compounds from the Final Premarket Tobacco Product Application Guidance. Yields were normalized to total device mass loss (DML). Collection strategies that consisted of partial pod collection were valid for determining yields of constituents whose DML normalized yields were consistent for the duration of pod life. These included primary aerosol constituents, such as propylene glycol, glycerol, and nicotine, and whole pod yields could be determined from initial puff blocks. However, changes were observed in the yields of some metals, some carbonyl compounds, and glycidol over pod life in a chemical constituent and product dependent manner. These results suggest that collection strategies consisting of initial puff block collections require validation per chemical constituent/product and are not appropriate for chemical constituents with variable yields over pod life. Whole pod collection increased sensitivity and accuracy in determining metal, carbonyl, and glycidol yields compared to puff block-based collection methodologies for all products tested.
Advancement of regulating cellular signaling pathways in NSCLC target therapy via nanodrug
Authors: Li Wenqiang , Li Mei , Huang Qian , He Xiaoyu , Shen Chen , Hou Xiaoming , Xue Fulai , Deng Zhiping , Luo Yao
Published: September 2023

Lung cancer (LC) is one of the leading causes of high cancer-associated mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common type of LC. The mechanisms of NSCLC evolution involve the alterations of multiple complex signaling pathways. Even with advances in biological understanding, early diagnosis, therapy, and mechanisms of drug resistance, many dilemmas still need to face in NSCLC treatments. However, many efforts have been made to explore the pathological changes of tumor cells based on specific molecular signals for drug therapy and targeted delivery. Nano-delivery has great potential in the diagnosis and treatment of tumors. In recent years, many studies have focused on different combinations of drugs and nanoparticles (NPs) to constitute nano-based drug delivery systems (NDDS), which deliver drugs regulating specific molecular signaling pathways in tumor cells, and most of them have positive implications. This review summarized the recent advances of therapeutic targets discovered in signaling pathways in NSCLC as well as the related NDDS, and presented the future prospects and challenges.
A lytic phage to control multidrug-resistant avian pathogenic Escherichia coli (APEC) infection
Authors: Yao Lan , Bao Yinli , Hu Jiangang , Zhang Beibei , Wang Zhiyang , Wang Xinyu , Guo Weiqi , Wang Di , Qi Jingjing , Tian Mingxing , Bao Yanqing , Li Haihua , Wang Shaohui
Published: September 2023

The inappropriate use of antibiotics has led to the emergence of multidrug-resistant strains. Bacteriophages (phages) have gained renewed attention as promising alternatives or supplements to antibiotics. In this study, a lytic avian pathogenic Escherichia coli (APEC) phage designated as PEC9 was isolated and purified from chicken farm feces samples. The morphology, genomic information, optimal multiplicity of infection (MOI), one-step growth curve, thermal stability, pH stability, in vitro antibacterial ability and biofilm formation inhibition ability of the phage were determined. Subsequently, the therapeutic effects of the phages were investigated in the mice model. The results showed that PEC9 was a member of the siphovirus-like by electron microscopy observation. Biological characterization revealed that it could lyse two serotypes of E. coli, including O1 (9/20) and O2 (6/20). The optimal multiplicity of infection (MOI) of phage PEC9 was 0.1. Phage PEC9 had a latent period of 20 min and a burst period of 40 min, with an average burst size of 68 plaque-forming units (PFUs)/cell. It maintained good lytic activity at pH 3-11 and 4-50°C and could efficiently inhibit the bacterial planktonic cell growth and biofilm formation, and reduce bacterial counts within the biofilm, when the MOI was 0.01, 0.1, and 1, respectively. Whole-genome sequencing showed that PEC9 was a dsDNA virus with a genome of 44379 bp and GC content of 54.39%. The genome contains 56 putative ORFs and no toxin, virulence, or resistance-related genes were detected. Phylogenetic tree analysis showed that PEC9 is closely related to E. coli phages vB_EcoS_Zar3M, vB_EcoS_PTXU06, SECphi18, ZCEC10, and ZCEC11, but most of these phages exhibit different gene arrangement. The phage PEC9 could successfully protect mice against APEC infection, including improved survival rate, reduced bacterial loads, and organ lesions. To conclude, our results suggest that phage PEC9 may be a promising candidate that can be used as an alternative to antibiotics in the control of APEC infection.
Fecal microbiota transplantation inhibited neuroinflammation of traumatic brain injury in mice via regulating the gut–brain axis
Authors: Hu Xuezhen , Jin Hangqi , Yuan Shushu , Ye Tao , Chen Zhibo , Kong Yu , Liu Jiaming , Xu Kaihong , Sun Jing
Published: September 2023

Introduction

Recent studies have highlighted the vital role of gut microbiota in traumatic brain injury (TBI). Fecal microbiota transplantation (FMT) is an effective means of regulating the microbiota–gut–brain axis, while the beneficial effect and potential mechanisms of FMT against TBI remain unclear. Here, we elucidated the anti-neuroinflammatory effect and possible mechanism of FMT against TBI in mice via regulating the microbiota–gut–brain axis.

Methods

The TBI mouse model was established by heavy object falling impact and then treated with FMT. The neurological deficits, neuropathological change, synaptic damage, microglia activation, and neuroinflammatory cytokine production were assessed, and the intestinal pathological change and gut microbiota composition were also evaluated. Moreover, the population of Treg cells in the spleen was measured.

Results

Our results showed that FMT treatment significantly alleviated neurological deficits and neuropathological changes and improved synaptic damage by increasing the levels of the synaptic plasticity-related protein such as postsynaptic density protein 95 (PSD-95) and synapsin I in the TBI mice model. Moreover, FMT could inhibit the activation of microglia and reduce the production of the inflammatory cytokine TNF-α, alleviating the inflammatory response of TBI mice. Meanwhile, FMT treatment could attenuate intestinal histopathologic changes and gut microbiota dysbiosis and increase the Treg cell population in TBI mice.

Conclusion

These findings elucidated that FMT treatment effectively suppressed the TBI-induced neuroinflammation via regulating the gut microbiota–gut–brain axis, and its mechanism was involved in the regulation of peripheral immune cells, which implied a novel strategy against TBI.
In-silico enhanced animal study of pulmonary artery pressure sensors: assessing hemodynamics using computational fluid dynamics
Authors: Brüning Jan , Yevtushenko Pavlo , Schlief Adriano , Jochum Tobias , van Gijzen Livia , Meine Sonja , Romberg Jan , Kuehne Titus , Arndt Andreas , Goubergrits Leonid
Published: September 2023

To assess whether in-silico models can be used to predict the risk of thrombus formation in pulmonary artery pressure sensors (PAPS), a chronic animal study using pigs was conducted. Computed tomography (CT) data was acquired before and immediately after implantation, as well as one and three months after the implantation. Devices were implanted into 10 pigs, each one in the left and right pulmonary artery (PA), to reduce the required number of animal experiments. The implantation procedure aimed at facilitating optimal and non-optimal positioning of the devices to increase chances of thrombus formation. Eight devices were positioned non-optimally. Three devices were positioned in the main PA instead of the left and right PA. Pre-interventional PA geometries were reconstructed from the respective CT images, and the devices were virtually implanted at the exact sites and orientations indicated by the follow-up CT after one month. Transient intra-arterial hemodynamics were calculated using computational fluid dynamics. Volume flow rates were modelled specifically matching the animals body weights. Wall shear stresses (WSS) and oscillatory shear indices (OSI) before and after device implantation were compared. Simulations revealed no relevant changes in any investigated hemodynamic parameters due to device implantation. Even in cases, where devices were implanted in a non-optimal manner, no marked differences in hemodynamic parameters compared to devices implanted in an optimal position were found. Before implantation time and surface-averaged WSS was 2.35±0.47 Pa, whereas OSI was 0.08±0.17, respectively. Areas affected by low WSS magnitudes were 2.5±2.7 cm2, whereas the areas affected by high OSI were 18.1±6.3 cm2. After device implantation, WSS and OSI were 2.45±0.49 Pa and 0.08±0.16, respectively. Surface areas affected by low WSS and high OSI were 2.9±2.7 cm2, and 18.4±6.1 cm2, respectively. This in-silico study indicates that no clinically relevant differences in intra-arterial hemodynamics are occurring after device implantation, even at non-optimal positioning of the sensor. Simultaneously, no embolic events were observed, suggesting that the risk for thrombus formation after device implantation is low and independent of the sensor position.
The propylitic alteration in the Ponce Enriquez Gold Mining district, Azuay province, Ecuador: genetic constraints from a mineral chemistry and fluid inclusions study
Authors: Fulignati Paolo , Mulas Maurizio , Villalta Echeverria Michelle Del Pilar , Fornasaro Silvia , Larreta Erwin , Mendoza Arteaga Pierina Lisbeth , Menoscal Menoscal Melanie Annabela , Romero-Crespo Paola , Gioncada Anna
Published: September 2023

Wide areas of the Southern sector of Ecuador are characterized by Cretaceous mafic volcanic rocks, pervasively altered by a propylitic mineralogical assemblage with epidote, chlorite, and quartz with minor titanite, illite and prehnite. These propylitically altered rocks host significant gold mineralization in veins, deeply exploited in the last decades. Porphyry Au-Cu deposits also occur in the area. This work focuses on the study of this propylitic alteration to assess the genetic conditions and the relation with the distance from the porphyry system, through the chemical composition of the secondary minerals (particularly trace elements in epidote and chlorite) and fluid inclusion data. The aim is to improve knowledge of the trace element geochemistry of secondary minerals in propylitic alteration and their relationship to the causative porphyry systems. The results of this work indicate that alteration affecting the rocks of the Pallatanga Fm. can be related to the propylitic hydrothermal alteration halo of porphyry copper deposits. Fluid inclusion investigation in quartz veins associated with epidote and chlorite evidenced at least two pulses of hydrothermal fluids characterized by temperature around 345°C for the first one and around 305°C for the second one. The salinity of the fluids is always low (around 1.5 wt% NaClequiv.) suggesting a dominantly meteoric component. Evidence of boiling processes have not been observed. We hypothesize that the hydrothermally altered “green rocks” of the Ponce Enriquez Mining District could be envisaged as the propylitic halo of the Miocene hornblende-bearing Au-Cu porphyry deposits of Gaby-Papa Grande, and discuss the epidote and chlorite trace element composition in this scenario. The results help improving the general knowledge of the propylitically altered rocks in southern Ecuador and add new data for the use of trace element chemistry of epidote and chlorite in mineral exploration elsewhere.
Association of alpha-aminoadipic acid with cardiometabolic risk factors in healthy and high-risk individuals
Authors: Desine Stacy , Gabriel Curtis L. , Smith Holly M. , Antonetti Olivia R. , Wang Chuan , Calcutt M. Wade , Doran Amanda C. , Silver Heidi J. , Nair Sangeeta , Terry James G. , Carr John Jeffrey , Linton MacRae F. , Brown Jonathan D. , Koethe John R. , Ferguson Jane F.
Published: September 2023

Introduction

Plasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease.

Methods

We measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort.

Results and discussion

We observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P<0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts, where high 2-AAA associated with low HDL cholesterol (P<0.001) and high triglycerides (P<0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P<0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P<0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P<0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations.
A network pharmacology and molecular docking approach to reveal the mechanism of Chaihu Anxin Capsule in depression
Authors: Yang Lin , Zhao Yan , Qu Ruochen , Fu Yan , Zhou Chunhua , Yu Jing
Published: September 2023

Introduction

As one of the most frequently diagnosed mental disorders, depression is expected to become the most common disease worldwide by 2030. Previous studies have shown that Chaihu Anxin Capsule has powerful antidepressant effects. However, its mechanisms are not fully understood. The aim of our research is to reveal the mechanisms of Chaihu Anxin Capsule in treating depression.

Methods

Information about the ingredients of the herb was gathered using the TCMSP. Genes associated with antidepressants were gathered from the GeneCards database. An “herbal-ingredient-target” network was constructed and analyzed using Cytoscape software. The PPI network of the antidepressant targets of Chaihu Anxin Capsule was constructed using the STRING database. KEGG pathway and GO enrichment were used to analyze the antidepressant targets. Molecular docking technology was used to confirm the capacity of the primary active ingredients of Chaihu Anxin Capsule to bind to central targets using AutoDock Vina and PyMOL software.

Results

Network analysis showed that five targets might be therapeutic targets of Chaihu Anxin Capsule in depression, namely, JUN, IL6, AKT1, TP53, and STAT3. The gene enrichment analysis implied that Chaihu Anxin Capsule benefits patients with depression by modulating pathways related to lipids and atherosclerosis and the AGE-RAGE signaling pathway in diabetic complications. Molecular docking analyses revealed that JUN, IL6, AKT1, TP53, and STAT3 had good affinities for quercetin, beta-sitosterol and kaempferol.

Conclusion

According to the bioinformatics data, the antidepressant effects of Chaihu Anxin Capsule may be primarily linked to cholesterol and atherosclerosis as well as the AGE-RAGE signaling pathway in diabetic complications. These results emphasize that the expected therapeutic targets may be possible indicators for antidepressant activity.
Research on energy sharing between distribution network and multiple systems based on the mixed game strategy and water-electric-gas integrated energy complementation
Authors: Shi Zhihan , Han Weisong , Zhang Guangming , Zhu Mingxiang , Bai Zhiqing , Lv Xiaodong
Published: September 2023

Introduction: It is significant for energy sharing to study the complementary utilization of multiple energy sources, such as water, electricity and gas, and the interaction among multiple stakeholders.

Methods: We propose a research on energy sharing between distribution network and multiple systems based on the mixed game strategy and water-electric-gas integrated energy complementation. Firstly, this paper describes the relationship and functions of all stakeholders under the research framework, and establishes the mathematical model of each unit in the water-electric-gas complementary IES. Secondly, the internal roles are layered based on the relationship between stakeholders in the system. Then a non-cooperative game model for the distribution network operator and multiple subsystems is established according to the theory of Stackelberg game, and a cooperative game model for multiple subsystems is further established based on the theory of Nash bargaining. In the next step, the complexity of the problem is analyzed, followed by the description of the specific algorithm and process of solving the model.

Results: Finally, the results of example analysis show that the model proposed in this paper not only balances the interests of stakeholders at the upper and lower layers of the system, but also allocates the interests of multiple subsystems at the lower layer.

Discussion: Thus effectively improving the energy utilization of the system.
MBMethPred: a computational framework for the accurate classification of childhood medulloblastoma subgroups using data integration and AI-based approaches
Authors: Sharif Rahmani Edris , Lawarde Ankita , Lingasamy Prakash , Moreno Sergio Vela , Salumets Andres , Modhukur Vijayachitra
Published: September 2023

Childhood medulloblastoma is a malignant form of brain tumor that is widely classified into four subgroups based on molecular and genetic characteristics. Accurate classification of these subgroups is crucial for appropriate treatment, monitoring plans, and targeted therapies. However, misclassification between groups 3 and 4 is common. To address this issue, an AI-based R package called MBMethPred was developed based on DNA methylation and gene expression profiles of 763 medulloblastoma samples to classify subgroups using machine learning and neural network models. The developed prediction models achieved a classification accuracy of over 96% for subgroup classification by using 399 CpGs as prediction biomarkers. We also assessed the prognostic relevance of prediction biomarkers using survival analysis. Furthermore, we identified subgroup-specific drivers of medulloblastoma using functional enrichment analysis, Shapley values, and gene network analysis. In particular, the genes involved in the nervous system development process have the potential to separate medulloblastoma subgroups with 99% accuracy. Notably, our analysis identified 16 genes that were specifically significant for subgroup classification, including EP300, CXCR4, WNT4, ZIC4, MEIS1, SLC8A1, NFASC, ASCL2, KIF5C, SYNGAP1, SEMA4F, ROR1, DPYSL4, ARTN, RTN4RL1, and TLX2. Our findings contribute to enhanced survival outcomes for patients with medulloblastoma. Continued research and validation efforts are needed to further refine and expand the utility of our approach in other cancer types, advancing personalized medicine in pediatric oncology.
Preclinical studies performed in appropriate models could help identify optimal timing of combined chemotherapy and immunotherapy
Authors: Berckmans Yani , Ceusters Jolien , Vankerckhoven Ann , Wouters Roxanne , Riva Matteo , Coosemans An
Published: September 2023

Immune checkpoint inhibitors (ICI) have been revolutionary in the field of cancer therapy. However, their success is limited to specific indications and cancer types. Recently, the combination treatment of ICI and chemotherapy has gained more attention to overcome this limitation. Unfortunately, many clinical trials testing these combinations have provided limited success. This can partly be attributed to an inadequate choice of preclinical models and the lack of scientific rationale to select the most effective immune-oncological combination. In this review, we have analyzed the existing preclinical evidence on this topic, which is only limitedly available. Furthermore, this preclinical data indicates that besides the selection of a specific drug and dose, also the sequence or order of the combination treatment influences the study outcome. Therefore, we conclude that the success of clinical combination trials could be enhanced by improving the preclinical set up, in order to identify the optimal treatment combination and schedule to enhance the anti-tumor immunity.
Integrated microRNA-mRNA analysis provides new insights into gonad coloration in the sea urchin Strongylocentrotus intermedius
Authors: Wu Boqiong , Jiao Renhe , Cui Dongyao , Zhao Tanjun , Song Jian , Zhan Yaoyao , Chang Yaqing
Published: September 2023

Comparative microRNA (miRNA) and mRNA transcriptome analyses were performed on Strongylocentrotus intermedius of the same sex with significant gonadal color differences. The results indicated that 1) the color of female gonads was generally superior to that of males. 2) Comparative and integrated miRNA and mRNA transcriptome analyses identified differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) in female and male individuals with significant gonadal color differences. Common and sex-specific DEGs and “DEM-DEG” pairs involved in carotenoid absorption, accumulation, and transformation were identified as candidates correlated with gonad coloration in S. intermedius. Collectively, the results from this study have enriched our knowledge of the process of sea urchin gonad coloration and should provide additional clues for increasing the gonad quality of commercial sea urchins from molecular and metabolic aspects.
Intraoperative application of regional cerebral oxygen saturation monitoring for geriatric patients in China: a survey
Authors: Zhang Jie , Shen Haiyan , Wang Huiping , Xiao Feng , Deng Lu , Chen Xiang , Xie Yongqiu
Published: September 2023

Background

Regional cerebral oxygen saturation (rSO2) monitoring is a real-time and non-invasive technique for estimating the balance of regional cerebral oxygen supply and consumption. Despite the growing popularity of this monitoring technique, data regarding outcome benefits remain sparse and contradictory. This study was conducted to explore the popularity and understanding of cerebral oxygen saturation monitoring during anesthesia in geriatric patients.

Methods

An online self-report questionnaire was distributed in March 2021 to various hospitals in China for dissemination to anesthesiologists. Questions surveyed cerebral oximetry equipment and utilization, demographics, and clinical practice of participants.

Results

In total, 447 anesthesiologists responded. Of these, 301 (67.3%) respondents reported that their hospitals were equipped with cerebral oximetry, which 274 anesthesiologists use during anesthesia. A high percentage of anesthesiologists chose to monitor rSO2 during cardiac surgery (77.4%, n = 212) and neurosurgery (40.5%, n = 111). Most anesthesiologists agreed that a 30% reduction from the rSO2 baseline requires intervention to avoid cerebral ischemia, mainly via elevating arterial pressure and fraction of inspired oxygen (FiO2). Of those without cerebral oximetry, 138 of 146 (94.5%) anesthesiologists were willing to monitor rSO2. In addition, 291 respondents believed that cerebral oxygen monitoring would help prevent postoperative cognitive dysfunction.

Conclusion

Our survey indicated that the prevalence of cerebral oximetry remains relatively low, while almost all anesthesiologists expressed their willingness to use rSO2 monitoring in geriatric anesthesia. Heterogeneity in clinical practice was identified, indicating relevant knowledge gaps that should encourage further clinical research to optimize treatment.
Impact of breastfeeding and other early-life factors on the development of the oral microbiome
Authors: Arishi Roaa A. , Lai Ching T. , Geddes Donna T. , Stinson Lisa F.
Published: September 2023

The oral cavity is home to the second most diverse microbiome in the human body. This community contributes to both oral and systemic health. Acquisition and development of the oral microbiome is a dynamic process that occurs over early life; however, data regarding longitudinal assembly of the infant oral microbiome is scarce. While numerous factors have been associated with the composition of the infant oral microbiome, early feeding practices (breastfeeding and the introduction of solids) appear to be the strongest determinants of the infant oral microbiome. In the present review, we draw together data on the maternal, infant, and environmental factors linked to the composition of the infant oral microbiome, with a focus on early nutrition. Given evidence that breastfeeding powerfully shapes the infant oral microbiome, the review explores potential mechanisms through which human milk components, including microbes, metabolites, oligosaccharides, and antimicrobial proteins, may interact with and shape the infant oral microbiome. Infancy is a unique period for the oral microbiome. By enhancing our understanding of oral microbiome assembly in early life, we may better support both oral and systemic health throughout the lifespan.
The variation characteristics of fecal microbiota in remission UC patients with anxiety and depression
Authors: Xu Lingyun , Li Yingchao , He Yingli
Published: September 2023

Background

Ulcerative colitis (UC) patients with relapsed disease are most likely to suffer from anxiety and depression. Increasing data indicates that psychological issues can change the composition of intestinal flora. Thus, we aim to seek the variation of intestinal microbiota composition in remission UC patients with anxiety and depression in Northwest China.

Results

In this study, 45 UC patients in remission were enrolled. The incidence of anxiety was 33.3%, and the prevalence of depression was 22.2%. There was no statistical difference in the alpha diversity of fecal microbiota, while beta diversity had a significant difference between the anxiety group and the non-anxiety group and the depression group and the non-depression group. Species composition analysis results showed that the ratio of Bifidobacterium and Lactobacilales significantly decreased. At the same time, the proportion of Escherichia-Shigella and Proteus_mirabilis increased in the anxiety group, and the ratio of Faecalibacterium and Bifidobacterium significantly decreased. In contrast, Escherichia-Shigella increased in the depression group at the gene levels.

Conclusion

Anxiety and depression still exist in UC patients even in the remission period. We first identify that the proportion of probiotics decreases while the proportion of pathogens increases in UC patients with anxiety and depression. These findings may provide a new pathophysiological mechanism for the recurrence of disease caused by impaired psychological function and a new method for the treatment strategy of UC patients with psychological issues.
An integrated transcriptomic and metabolic phenotype analysis to uncover the metabolic characteristics of a genetically engineered Candida utilis strain expressing δ-zein gene
Authors: He Qiburi , Gong Gaowa , Wan Tingting , Hu He , Yu Peng
Published: September 2023

Introduction

Candida utilis (C. utilis) has been extensively utilized as human food or animal feed additives. With its ability to support heterologous gene expression, C. utilis proves to be a valuable platform for the synthesis of proteins and metabolites that possess both high nutritional and economic value. However, there remains a dearth of research focused on the characteristics of C. utilis through genomic, transcriptomic and metabolic approaches.

Methods

With the aim of unraveling the molecular mechanism and genetic basis governing the biological process of C. utilis, we embarked on a de novo sequencing endeavor to acquire comprehensive sequence data. In addition, an integrated transcriptomic and metabolic phenotype analysis was performed to compare the wild-type C. utilis (WT) with a genetically engineered strain of C. utilis that harbors the heterologous δ-zein gene (RCT).

Results

δ-zein is a protein rich in methionine found in the endosperm of maize. The integrated analysis of transcriptomic and metabolic phenotypes uncovered significant metabolic diversity between the WT and RCT C. utilis. A total of 252 differentially expressed genes were identified, primarily associated with ribosome function, peroxisome activity, arginine and proline metabolism, carbon metabolism, and fatty acid degradation. In the experimental setup using PM1, PM2, and PM4 plates, a total of 284 growth conditions were tested. A comparison between the WT and RCT C. utilis demonstrated significant increases in the utilization of certain carbon source substrates by RCT. Gelatin and glycogen were found to be significantly utilized to a greater extent by RCT compared to WT. Additionally, in terms of sulfur source substrates, RCT exhibited significantly increased utilization of O-Phospho-L-Tyrosine and L-Methionine Sulfone when compared to WT.

Discussion

The introduction of δ-zein gene into C. utilis may lead to significant changes in the metabolic substrates and metabolic pathways, but does not weaken the activity of the strain. Our study provides new insights into the transcriptomic and metabolic characteristics of the genetically engineered C. utilis strain harboring δ-zein gene, which has the potential to advance the utilization of C. utilis as an efficient protein feed in agricultural applications.
Impact of e-ASPECTS software on the performance of physicians compared to a consensus ground truth: a multi-reader, multi-case study
Authors: Kobeissi Hassan , Kallmes David F. , Benson John , Nagelschneider Alex , Madhavan Ajay , Messina Steven A. , Schwartz Kara , Campeau Norbert , Carr Carrie M. , Nasr Deena M. , Braksick Sherri , Scharf Eugene L. , Klaas James , Woodhead Zoe Victoria Joan , Harston George , Briggs James , Joly Olivier , Gerry Stephen , Kuhn Anna L. , Kostas Angelos A. , Nael Kambiz , AbdalKader Mohamad , Kadirvel Ramanathan , Brinjikji Waleed
Published: September 2023

Background

The Alberta Stroke Program Early CT Score (ASPECTS) is used to quantify the extent of injury to the brain following acute ischemic stroke (AIS) and to inform treatment decisions. The e-ASPECTS software uses artificial intelligence methods to automatically process non-contrast CT (NCCT) brain scans from patients with AIS affecting the middle cerebral artery (MCA) territory and generate an ASPECTS. This study aimed to evaluate the impact of e-ASPECTS (Brainomix, Oxford, UK) on the performance of US physicians compared to a consensus ground truth.

Methods

The study used a multi-reader, multi-case design. A total of 10 US board-certified physicians (neurologists and neuroradiologists) scored 54 NCCT brain scans of patients with AIS affecting the MCA territory. Each reader scored each scan on two occasions: once with and once without reference to the e-ASPECTS software, in random order. Agreement with a reference standard (expert consensus read with reference to follow-up imaging) was evaluated with and without software support.

Results

A comparison of the area under the curve (AUC) for each reader showed a significant improvement from 0.81 to 0.83 (p = 0.028) with the support of the e-ASPECTS tool. The agreement of reader ASPECTS scoring with the reference standard was improved with e-ASPECTS compared to unassisted reading of scans: Cohen's kappa improved from 0.60 to 0.65, and the case-based weighted Kappa improved from 0.70 to 0.81.

Conclusion

Decision support with the e-ASPECTS software significantly improves the accuracy of ASPECTS scoring, even by expert US neurologists and neuroradiologists.
Stem cells as potential therapeutics for hearing loss
Authors: Fang Qiaojun , Wei Yongjie , Zhang Yuhua , Cao Wei , Yan Lin , Kong Mengdie , Zhu Yongjun , Xu Yan , Guo Lingna , Zhang Lei , Wang Weiqing , Yu Yafeng , Sun Jingwu , Yang Jianming
Published: September 2023

Hearing impairment is a global health problem. Stem cell therapy has become a cutting-edge approach to tissue regeneration. In this review, the recent advances in stem cell therapy for hearing loss have been discussed. Nanomaterials can modulate the stem cell microenvironment to augment the therapeutic effects further. The potential of combining nanomaterials with stem cells for repairing and regenerating damaged inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) has also been discussed. Stem cell-derived exosomes can contribute to the repair and regeneration of damaged tissue, and the research progress on exosome-based hearing loss treatment has been summarized as well. Despite stem cell therapy’s technical and practical limitations, the findings reported so far are promising and warrant further investigation for eventual clinical translation.
Case Report: ASXL1, RUNX1, and IDH1 mutation in tyrosine kinase-independent resistant chronic myeloid leukemia progressing to chronic myelomonocytic leukemia-like accelerated phase
Authors: Oyogoa Emmanuella , Streich Lukas , Raess Philipp W. , Braun Theodore
Published: September 2023

Although the majority of patients with chronic myeloid leukemia (CML) enjoy an excellent prognosis tyrosine kinase inhibitor (TKI) therapy, resistance remains a significant clinical problem. Resistance can arise from mutations in the kinase domain of ABL preventing drug binding, or due to ill-defined kinase-independent mechanisms. In this case report, we describe the case of a 27-year-old woman with a long-standing history of chronic phase (CP) CML who developed kinase-independent resistance with mutations in ASXL1 and RUNX1. As a consequence of uncontrolled disease, she progressed to a chronic myelomonocytic leukemia-like (CMML) accelerated phase (AP) disease with the acquisition of a mutation in IDH1. This disease progression was associated with the development of an inflammatory serositis, a phenomenon that has been described in CMML but not in AP-CML. This case presents key features of kinase-independent resistance with insight into potential mechanisms, highlights management challenges, and describes a novel systemic inflammatory response that occurred in this patient upon disease progression.
Role of cytokine in malignant T-cell metabolism and subsequent alternation in T-cell tumor microenvironment
Authors: Yadav Megha , Uikey Blessi N. , Rathore Shantnu Singh , Gupta Priyanka , Kashyap Diksha , Kumar Chanchal , Shukla Dhananjay , Vijayamahantesh  , Chandel Arvind Singh , Ahirwar Bharti , Singh Ashish Kumar , Suman Shashi Shekhar , Priyadarshi Amit , Amit Ajay
Published: September 2023

T cells are an important component of adaptive immunity and T-cell-derived lymphomas are very complex due to many functional sub-types and functional elasticity of T-cells. As with other tumors, tissues specific factors are crucial in the development of T-cell lymphomas. In addition to neoplastic cells, T- cell lymphomas consist of a tumor micro-environment composed of normal cells and stroma. Numerous studies established the qualitative and quantitative differences between the tumor microenvironment and normal cell surroundings. Interaction between the various component of the tumor microenvironment is crucial since tumor cells can change the microenvironment and vice versa. In normal T-cell development, T-cells must respond to various stimulants deferentially and during these courses of adaptation. T-cells undergo various metabolic alterations. From the stage of quiescence to attention of fully active form T-cells undergoes various stage in terms of metabolic activity. Predominantly quiescent T-cells have ATP-generating metabolism while during the proliferative stage, their metabolism tilted towards the growth-promoting pathways. In addition to this, a functionally different subset of T-cells requires to activate the different metabolic pathways, and consequently, this regulation of the metabolic pathway control activation and function of T-cells. So, it is obvious that dynamic, and well-regulated metabolic pathways are important for the normal functioning of T-cells and their interaction with the microenvironment. There are various cell signaling mechanisms of metabolism are involved in this regulation and more and more studies have suggested the involvement of additional signaling in the development of the overall metabolic phenotype of T cells. These important signaling mediators include cytokines and hormones. The impact and role of these mediators especially the cytokines on the interplay between T-cell metabolism and the interaction of T-cells with their micro-environments in the context of T-cells lymphomas are discussed in this review article.
The prevalence and outcomes of hyponatremia in children with COVID-19 and multisystem inflammatory syndrome in children (MIS-C)
Authors: Dalal Neal , Pfaff Mairead , Silver Layne , Glater-Welt Lily , Sethna Christine , Singer Pamela , Castellanos-Reyes Laura , Basalely Abby
Published: September 2023

Introduction

To assess the prevalence of hyponatremia among pediatric patients with coronavirus disease 2019 (COVID-19) and Multisystem Inflammatory Syndrome in Children (MIS-C) and determine if pediatric hyponatremia was associated with an increased length of stay, higher rates of mechanical ventilation, and/or elevated inflammatory markers on admission as compared to eunatremic patients.

Methods

Electronic health records were retrospectively analyzed for 168 children less than 18 years old with COVID-19 or MIS-C who were admitted to pediatric units within the Northwell Health system. The primary exposure was hyponatremic status (serum sodium <135 mEq/L) and the primary outcomes were length of stay, mechanical ventilation usage and increased inflammatory markers.

Results

Of the 168 children in the study cohort, 95 (56%) were admitted for COVID-19 and 73 (43.5%) for MIS-C. Overall, 60 (35.7%) patients presented with hyponatremia on admission. Patients with hyponatremia had higher rates of intensive care unit admission when compared to eunatremic patients (32/60 [53.3%] vs. 39/108 [36.1%], p = 0.030). In regression models, hyponatremia was not significantly associated with increased length of stay or mechanical ventilation rates. After adjustment for relevant confounders, hyponatremia remained associated with an increased square root CRP (β = 1.79: 95% CI: 0.22–3.36) and lower albumin levels (β = −0.22: 95% CI: −0.42–−0.01).

Conclusion

Hyponatremia is common in pediatric COVID-19 and MIS-C. Hyponatremia was associated with a lower albumin and higher square root CRP levels. This may suggest an association of inflammation with lower serum sodium levels.
Invasive alien plants are phylogenetically distinct from other alien species across spatial and taxonomic scales in China
Authors: Banerjee Achyut Kumar , Tan Fengxiao , Feng Hui , Liang Xinru , Wang Jiakai , Yin Minghui , Peng Hao , Lin Yuting , Zhang Nannan , Huang Yelin
Published: September 2023

Introduction

Phylogenetic relatedness is one of the important factors in the community assembly process. Here, we aimed to understand the large-scale phylogenetic relationship between alien plant species at different stages of the invasion process and how these relationships change in response to the environmental filtering process at multiple spatial scales and different phylogenetic extents.

Methods

We identified the alien species in three invasion stages, namely invasive, naturalized, and introduced, in China. The occurrence records of the species were used to quantify two abundance-based phylogenetic metrics [the net relatedness index (NRI) and the nearest taxon index (NTI)] from a highly resolved phylogenetic tree. The metrics were compared between the three categories of alien species. Generalized linear models were used to test the effect of climate on the phylogenetic pattern. All analyses were conducted at four spatial scales and for three major angiosperm families.

Results

We observed significantly higher NRI and NTI values at finer spatial scales, indicating the formation of more clustered assemblages of phylogenetically closely related species in response to the environmental filtering process. Positive NTI values for the invasive and naturalized aliens suggested that the presence of a close relative in the community may help the successful naturalization and invasion of the introduced alien species. In the two-dimensional phylogenetic space, the invasive species communities significantly differed from the naturalized and introduced species, indicating that established alien species need to be phylogenetically different to become invasive. Positive phylogenetic measures for the invasive aliens across the spatial scales suggested that the presence of invasive aliens could facilitate the establishment of other invasive species. Phylogenetic relatedness was more influenced by temperature than precipitation, especially at a finer spatial scale. With decreased temperature, the invasive species showed a more clustered assemblage, indicating conservatism of their phylogenetic niche. The phylogenetic pattern was different at the family level, although there was a consistent tendency across families to form more clustered assemblages.

Discussion

Overall, our study showed that the community assemblage became more clustered with the progression of the invasion process. The phylogenetic measures varied at spatial and taxonomic scales, thereby highlighting the importance of assessing phylogenetic patterns at different gradients of the community assembly process.
When shapes are more than shapes: perceptual, developmental, and neurophysiological basis for attributions of animacy and theory of mind
Authors: Torabian Sajjad , Grossman Emily D.
Published: September 2023

Among a variety of entities in their environment, what do humans consider alive or animate and how does this attribution of animacy promote development of more abstract levels of mentalizing? By decontextualizing the environment of bodily features, we review how physical movements give rise to perceived animacy in Heider-Simmel style animations. We discuss the developmental course of how perceived animacy shapes our interpretation of the social world, and specifically discuss when and how children transition from perceiving actions as goal-directed to attributing behaviors to unobservable mental states. This transition from a teleological stance, asserting a goal-oriented interpretation to an agent's actions, to a mentalistic stance allows older children to reason about more complex actions guided by hidden beliefs. The acquisition of these more complex cognitive behaviors happens developmentally at the same time neural systems for social cognition are coming online in young children. We review perceptual, developmental, and neural evidence to identify the joint cognitive and neural changes associated with when children begin to mentalize and how this ability is instantiated in the brain.