bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel hypoxia- and lactate metabolism-related prognostic signature to characterize the immune landscape and predict immunotherapy response in osteosarcoma
Authors: Wang Yizhuo , Wang Xin , Liu Yang , Xu Jiayuan , Zhu Jiyuan , Zheng Yufu , Qi Quan
Published: November 2024

Background

Immunotherapy has shown considerable promise in cancer treatment, yet only a minority of osteosarcoma patients derive benefits from this approach. Hypoxia and lactate metabolism are two predominant characteristics of the tumor microenvironment. These features are crucial for molding the immune landscape and thus have the potential to act as predictive indicators for immunotherapy response.

Methods

Prognostic modeled genes were identified through univariate and multivariate Cox regression as well as LASSO regression analyses. The tumor microenvironment was evaluated using ESTIMATE, CIBERSORT, and ImmuCellAI analyses. Tide prediction and expression of immune checkpoints, MHC molecules, chemokines, interleukins, interferons, receptors, and other cytokines were utilized to estimate immunotherapy efficacy. Single-cell analysis was performed to demonstrate the expression of modeled genes among various immune cell types. Experimental validation was carried out to verify the expression and functions of SFXN4 and SQOR.

Results

A potent signature was constructed with 8 genes related to hypoxia and lactate metabolism, including MAFF, COL5A2, FAM162A, SQOR, UQCRB, SFXN4, PFKFB2 and COX6A2. A nomogram incorporating risk scores and other clinical features demonstrated excellent predictive capacity. Osteosarcoma patients with high-risk scores exhibited poor prognosis and more “cold” tumor characteristics. According to the ESTIMATE algorithm, these patients displayed lower immune, stromal, and ESTIMATE scores, partially attributed to inadequate infiltration of key immunocytes. The Ciborsort analysis similarly indicated that high-risk individuals had diminished infiltration of critical anti-tumor immune cells such as Cytotoxic T cells, CD4+ T cells, and NK cells. The low expression levels of certain immune checkpoints, MHC molecules, chemokines, interleukins, interferons, receptors, and other cytokines in high-risk cases suggested their unsatisfactory responses to immune treatment. Tide prediction further demonstrated that fewer individuals classified as high risk may exhibit sensitivity to immune checkpoint inhibitor therapy. Notably, SFXN4 was found to be highly expressed in osteosarcoma tissues and cells; it promoted the growth, migration, and invasion of osteosarcoma cells, while SQOR had the opposite effect.

Conclusion

Our research has developed a robust hypoxia- and lactate metabolism-related gene signature, providing a solid theoretical foundation for prognosis prediction, classification of “cold” and “hot” tumors, accessing immunotherapy response, and directing personalized treatment for osteosarcoma.
A case report of severe drug-induced immune hemolytic anemia caused by piperacillin
Authors: Zhao Hong , Chen Jian , Ou Guojin
Published: November 2024

Piperacillin is a beta-lactamase inhibitor frequently used in the treatment of urinary tract infections. It is a broad-spectrum antibiotic with strong antibacterial action against Pseudomonas aeruginosa and Enterobacter, especially extended-spectrum beta-lactamase-producing Enterobacteria and Enterococcus. Side effects of piperacillin include allergic reactions, rashes such as urticaria, leukopenia, interstitial nephritis, asthma attacks, serological reactions, candida infection, and bleeding with more severe reactions resulting in anaphylactic shock. Anemia and hemolytic anemia are rare adverse reactions to piperacillin, with an incidence of 0.01–0.10%. We report herein the case of a severe postoperative immune hemolytic reaction to piperacillin. Fortunately, we quickly recognized and identified the drug reaction caused by piperacillin, immediately stopped the use of piperacillin, and performed a blood transfusion. The patient recovered and was subsequently discharged from the hospital.
Determination of immunogenicity of an inactivated ND-vaccine developed experimentally with Newcastle disease virus (Genotype VII.2) local isolates of Bangladesh
Authors: Haque Mohammad Aynul , Haque Md. Enamul , Parvin Mst. Kohinoor , Kamal Md. Mostofa , Islam Tanbin Rubaiya , Sadekuzzaman Mohammad , Islam Md. Ariful , Khatun Mst. Minara , Hossain Muhammad Tofazzal , Uddin Mohammad Asir , Nahar Sham Soun , Khasruzzaman A. K. M. , Islam Md. Alimul
Published: November 2024

Background

Newcastle disease virus (NDV) genotype VII severely affects poultry, causing respiratory and neurological symptoms with a high rate of morbidity and mortality. The research aimed to develop an inactivated ND vaccine using local isolates (Genotype VII.2) and assess its immunogenicity compared to other commercial live ND vaccines.

Methods

An inactivated vaccine using a candidate NDV (GenBank: OR924274.1) was developed according to WOAH guidelines following inactivation, sterility, purity, and safety tests. The birds were vaccinated through subcutaneous (SC) and intramuscular (IM) routes using three doses (0.25, 0.5, and 1.0 ml/bird). Immunogenicity and protective potentiality of the experimentally developed inactivated ND vaccine and live commercial ND vaccine (intra-ocularly/IO) were compared by challenge studies using three vaccination schedules: killed-followed-killed, live-followed-killed, and live-followed-live.

Results

The birds vaccinated with 1.0 ml/bird SC showed higher antibody titers compared to those of IM-vaccinated groups. Birds vaccinated with the live-followed-killed commercial ND vaccines had slightly higher antibody titers compared to those vaccinated with killed-followed-killed and live-followed-live vaccines. Birds vaccinated with the killed-followed-killed ND vaccine showed a higher protection rate (100%) compared to live-followed-killed (83±5.77%) and live-followed-live (57±5.77%) vaccines. Birds vaccinated with killed-followed-killed group showed a slower decline rate of antibody titers than other groups. This regimen provided significantly better immunity, highlighting its potential in controlling ND outbreaks in Bangladesh's poultry.

Conclusion

The study found that the inactivated ND vaccine, developed with the locally circulating isolate of genotype-VII.2 of NDV, might play an important role in effective control and management of ND in the commercial poultry population in Bangladesh.
Association of artificial intelligence-based immunoscore with the efficacy of chemoimmunotherapy in patients with advanced non-squamous non-small cell lung cancer: a multicentre retrospective study
Authors: Liu Jiaqing , Sun Dongchen , Xu Shuoyu , Shen Jiayi , Ma Wenjuan , Zhou Huaqiang , Ma Yuxiang , Zhang Yaxiong , Fang Wenfeng , Zhao Yuanyuan , Hong Shaodong , Zhan Jianhua , Hou Xue , Zhao Hongyun , Huang Yan , He Bingdou , Yang Yunpeng , Zhang Li
Published: November 2024

Purpose

Currently, chemoimmunotherapy is effective only in a subset of patients with advanced non-squamous non-small cell lung cancer. Robust biomarkers for predicting the efficacy of chemoimmunotherapy would be useful to identify patients who would benefit from chemoimmunotherapy. The primary objective of our study was to develop an artificial intelligence-based immunoscore and to evaluate the value of patho-immunoscore in predicting clinical outcomes in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

Methods

We have developed an artificial intelligence–powered immunoscore analyzer based on 1,333 whole-slide images from TCGA-LUAD. The predictive efficacy of the model was further validated in the CPTAC-LUAD cohort and the biomarker cohort of the ORIENT-11 study, a randomized, double-blind, phase 3 study. Finally, the clinical significance of the patho-immunoscore was evaluated using the ORIENT-11 study cohort.

Results

Our immunoscore analyzer achieved good accuracy in all the three cohort mentioned above (TCGA-LUAD, mean AUC: 0.783; ORIENT-11 cohort, AUC: 0.741; CPTAC-LUAD cohort, AUC: 0.769). In the 259 patients treated with chemoimmunotherapy, those with high patho-immunoscore (n = 146) showed significantly longer median progression-free survival than those with low patho-immunoscore (n = 113) (13.8 months vs 7.13 months, hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.38 – 0.73; p < 0.001). In contrast, no significant difference was observed in patients who were treated with chemotherapy only (5.07 months vs 5.07 months, HR: 1.04, 95% CI: 0.71 – 1.54; p = 0.83). Similar trends were observed in overall survival.

Conclusion

Our study indicates that AI-powered immunoscore applied on LUAD digital slides can serve as a biomarker for survival outcomes in patients with advanced non-squamous NSCLC who received chemoimmunotherapy. This methodology could be applied to other cancers and facilitate cancer immunotherapy.
CAR-T cell therapy for hepatocellular carcinoma: current trends and challenges
Authors: Zhou Yexin , Wei Shanshan , Xu Menghui , Wu Xinhui , Dou Wenbo , Li Huakang , Zhang Zhonglin , Zhang Shuo
Published: November 2024

Hepatocellular carcinoma (HCC) ranks among the most prevalent cancers worldwide, highlighting the urgent need for improved diagnostic and therapeutic methodologies. The standard treatment regimen generally involves surgical intervention followed by systemic therapies; however, the median survival rates for patients remain unsatisfactory. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a pivotal advancement in cancer treatment. Both clinical and preclinical studies emphasize the notable efficacy of CAR T cells in targeting HCC. Various molecules, such as GPC3, c-Met, and NKG2D, show significant promise as potential immunotherapeutic targets in liver cancer. Despite this, employing CAR T cells to treat solid tumors like HCC poses considerable challenges within the discipline. Numerous innovations have significant potential to enhance the efficacy of CAR T-cell therapy for HCC, including improvements in T cell trafficking, strategies to counteract the immunosuppressive tumor microenvironment, and enhanced safety protocols. Ongoing efforts to discover therapeutic targets for CAR T cells highlight the need for the development of more practical manufacturing strategies for CAR-modified cells. This review synthesizes recent findings and clinical advancements in the use of CAR T-cell therapies for HCC treatment. We elucidate the therapeutic benefits of CAR T cells in HCC and identify the primary barriers to their broader application. Our analysis aims to provide a comprehensive overview of the current status and future prospects of CAR T-cell immunotherapy for HCC.
Mechanisms and treatment of atherosclerosis: focus on macrophages
Authors: Zhang LingNa , Li JiaWei , Kou YuShun , Shen LuFan , Wang Hong , Wang YiYuan , Ma Ruiling , Wu Tao , Yang Xin , Gu YuanHui , Yi Lin
Published: November 2024

Macrophages are the basic mediators and coordinators of various types of chronic inflammation and play a crucial role in the formation and development of atherosclerosis (AS). In the complex microenvironment of atherosclerotic plaques, macrophages of different sources are exposed to different signal stimuli and thus polarized into various subpopulations. Various types of macrophages with predominantly M1 and M2 phenotypes also play different regulatory roles in the initiation and progression of AS. Lipid-lowering drugs, mainly statins, are widely used in clinical practice, but the adverse reactions are obvious and there is a lack of personalized treatment. Emerging targeted macrophage and Traditional Chinese medicine (TCM)-related therapies can regulate the cellular microenvironment, inhibit the polarization of M1 macrophages, and promote the activation of M2 macrophages, providing new ideas for the prevention and treatment of AS.
Case Report: Crosstalk between systemic lupus erythematosus and sickle cell syndromes—two cases from eastern India
Authors: Das Dhriti Sundar
Published: November 2024

Autoimmune diseases and sickle cell abnormalities have been reported to share some common pathogenic pathways. Here, we describe two cases of individuals with sickle cell trait (SCT) who presented with antibodies to antinuclear antigens and clinical features consistent with systemic lupus erythematosus (SLE). These patients were from the eastern state of India, i.e., Odisha. Both patients had documented sickle cell trait and tested positive for anti-double-stranded DNA antibodies. They presented with lupus nephritis without any obvious features of sickle cell hemoglobinopathies. Crosstalk between SLE and SCT may explain this association, which needs validation in future large-scale studies.
Comparative analysis of climate-induced habitat shift of economically significant species with diverse ecological preferences in the Northwest Pacific
Authors: Dong Wanchuan , Bai Xinlu , Zhao Linlin , Dong Hao , Liu Changdong
Published: November 2024

The Northwest Pacific Ocean is the most productive fishing ground in the Pacific Ocean, with a continuous rise in water temperature since 1990. We developed stacked species distribution models (SSDMs) to estimate the impacts of climate change on the distribution dynamics of economically significant species under three climate change scenarios for the periods 2040-2060 and 2080-2100. Overall, water temperature is the most important factor in shaping the distribution patterns of species, followed by water depth. The predictive results indicate that all the species show a northward migration in the future, and the migration distance varies greatly among species. Most pelagic species will expand their habitats under climate change, implying their stronger adaptability than benthic species. Tropical fishes are more adaptable to climate change than species in other climate zones. Though limitations existed, our study provided baseline information for designing a climate-adaptive, dynamic fishery management strategy for maintaining sustainable fisheries.
Potential diagnostic markers and therapeutic targets for non-alcoholic fatty liver disease and ulcerative colitis based on bioinformatics analysis and machine learning
Authors: Luo Zheng , Huang Cong , Chen Jilan , Chen Yunhui , Yang Hongya , Wu Qiaofeng , Lu Fating , Zhang Tian E.
Published: November 2024

Background

Non-alcoholic fatty liver disease (NAFLD) and ulcerative colitis (UC) are two common health issues that have gained significant global attention. Previous studies have suggested a possible connection between NAFLD and UC, but the underlying pathophysiology remains unclear. This study investigates common genes, underlying pathogenesis mechanisms, identification of diagnostic markers applicable to both conditions, and exploration of potential therapeutic targets shared by NAFLD and UC.

Methods

We obtained datasets for NAFLD and UC from the GEO database. The DEGs in the GSE89632 dataset of the NAFLD and GSE87466 of the UC dataset were analyzed. WGCNA, a powerful tool for identifying modules of highly correlated genes, was employed for both datasets. The DEGs of NAFLD and UC and the modular genes were then intersected to obtain shared genes. Functional enrichment analysis was conducted on these shared genes. Next, we utilize the STRING database to establish a PPI network. To enhance visualization, we employ Cytoscape software. Subsequently, the Cytohubba algorithm within Cytoscape was used to identify central genes. Diagnostic biomarkers were initially screened using LASSO regression and SVM methods. The diagnostic value of ROC curve analysis was assessed to detect diagnostic genes in both training and validation sets for NAFLD and UC. A nomogram was also developed to evaluate diagnostic efficacy. Additionally, we used the CIBERSORT algorithm to explore immune infiltration patterns in both NAFLD and UC samples. Finally, we investigated the correlation between hub gene expression, diagnostic gene expression, and immune infiltration levels.

Results

We identified 34 shared genes that were found to be associated with both NAFLD and UC. These genes were subjected to enrichment analysis, which revealed significant enrichment in several pathways, including the IL-17 signaling pathway, Rheumatoid arthritis, and Chagas disease. One optimal candidate gene was selected through LASSO regression and SVM: CCL2. The ROC curve confirmed the presence of CCL2 in both the NAFLD and UC training sets and other validation sets. This finding was further validated using a nomogram in the validation set. Additionally, the expression levels of CCL2 for NAFLD and UC showed a significant correlation with immune cell infiltration.

Conclusion

This study identified a gene (CCL2) as a biomarker for NAFLD and UC, which may actively participate in the progression of NAFLD and UC. This discovery holds significant implications for understanding the progression of these diseases and potentially developing more effective diagnostic and treatment strategies.
Gut dysbiosis mediates the association between antibiotic exposure and chronic disease
Authors: Guarner Francisco , Bustos Fernandez Luis , Cruchet Sylvia , Damião Adérson , Maruy Saito Aldo , Riveros Lopez Juan Pablo , Rodrigues Silva Luciana , Valdovinos Diaz Miguel Angel
Published: November 2024

Antibiotics are safe, effective drugs and continue to save millions of lives and prevent long-term illness worldwide. A large body of epidemiological, interventional and experimental evidence shows that exposure to antibiotics has long-term negative effects on human health. We reviewed the literature data on the links between antibiotic exposure, gut dysbiosis, and chronic disease (notably with regard to the “developmental origins of health and disease” (“DOHaD”) approach). Molecular biology studies show that the systemic administration of antibiotic to infants has a rapid onset but also often a long-lasting impact on the microbial composition of the gut. Along with other environmental factors (e.g., an unhealthy “Western” diet and sedentary behavior), antibiotics induce gut dysbiosis, which can be defined as the disruption of a previously stable, functionally complete microbiota. Gut dysbiosis many harmful long-term effects on health. Associations between early-life exposure to antibiotics have been reported for chronic diseases, including inflammatory bowel disease, celiac disease, some cancers, metabolic diseases (obesity and type 2 diabetes), allergic diseases, autoimmune disorders, atherosclerosis, arthritis, and neurodevelopmental, neurodegenerative and other neurological diseases. In mechanistic terms, gut dysbiosis influences chronic disease through direct effects on mucosal immune and inflammatory pathways, plus a wide array of direct or indirect effects of short-chain fatty acids, the enteric nervous system, peristaltic motility, the production of hormones and neurotransmitters, and the loss of intestinal barrier integrity (notably with leakage of the pro-inflammatory endotoxin lipopolysaccharide into the circulation). To mitigate dysbiosis, the administration of probiotics in patients with chronic disease is often (but not always) associated with positive effects on clinical markers (e.g., disease scores) and biomarkers of inflammation and immune activation. Meta-analyses are complicated by differences in probiotic composition, dose level, and treatment duration, and large, randomized, controlled clinical trials are lacking in many disease areas. In view of the critical importance of deciding whether or not to prescribe antibiotics (especially to children), we suggest that the DOHaD concept can be logically extended to “gastrointestinal origins of health and disease” (“GOHaD”) or even “microbiotic origins of health and disease” (“MOHaD”).
BreCML: identifying breast cancer cell state in scRNA-seq via machine learning
Authors: Ke Shanbao , Huang Yuxuan , Wang Dong , Jiang Qiang , Luo Zhangyang , Li Baiyu , Yan Danfang , Zhou Jianwei
Published: November 2024

Breast cancer is a prevalent malignancy and one of the leading causes of cancer-related mortality among women worldwide. This disease typically manifests through the abnormal proliferation and dissemination of malignant cells within breast tissue. Current diagnostic and therapeutic strategies face significant challenges in accurately identifying and localizing specific subtypes of breast cancer. In this study, we developed a novel machine learning-based predictor, BreCML, designed to accurately classify subpopulations of breast cancer cells and their associated marker genes. BreCML exhibits outstanding predictive performance, achieving an accuracy of 98.92% on the training dataset. Utilizing the XGBoost algorithm, BreCML demonstrates superior accuracy (98.67%), precision (99.15%), recall (99.49%), and F1-score (99.79%) on the test dataset. Through the application of machine learning and feature selection techniques, BreCML successfully identified new key genes. This predictor not only serves as a powerful tool for assessing breast cancer cellular status but also offers a rapid and efficient means to uncover potential biomarkers, providing critical insights for precision medicine and therapeutic strategies.
Changes in clinical features and seasonal variations of Crohn’s disease at diagnosis: a 10-year observational study in China
Authors: Deng Jun , Lu Yi , Liu Tao , Zhang Min , Yao Jia-yin , Zhi Min
Published: November 2024

Background and aims

The clinical aspects of Crohn’s disease (CD) at diagnosis determine its therapy and management. The onset of CD follows a seasonal pattern. We aimed to analyze changes in the clinical features and seasonal variations of newly CD patients over the last decade.

Methods

CD patients were divided into cohort 1 (2012–2016) and cohort 2 (2017–2021). The clinical characteristics were collected and the trends according to the year and season of diagnosis were analyzed.

Results

A total of 2038 patients were included. Cohort 1 had a considerably greater proportion of diarrhea, fever, hematochezia, weight loss and extraintestinal manifestations. The levels of platelet and C-reactive protein were higher in cohort 2 patients, but the opposite was true for albumin levels (p<0.05). The rate of increased eosinophils, increased gangliocyte and abundant lymphoplasmacytic infiltrate significantly decreased over the years. Patients with granulomas were diagnosed with CD at an earlier age (p = 0.006). Cohort 1 patients used more conventional drugs, while cohort 2 patients apply more biologics (p<0.05). The diagnosis occurred more frequently in summer and less frequently in winter. Patients diagnosed in winter had notably higher BMI, lower frequency of perianal disease and lowest incidence of asthenia and weight loss.

Conclusion

The clinical phenotype, laboratory and pathological characteristics of CD has changed over time in China. The diagnosis of CD tends to have a seasonal trend with the highest incidence in summer. CD patients diagnosed in winter appear to have a milder form of the disease.
Association between duration of phenoxybenzamine use and postoperative delirium in suspected adrenal pheochromocytoma: a retrospective cohort study
Authors: Wang Qunying , Huang Fusen , Wei Ke , Wang Jingjie , Zhu Xin , Xiong Qiuju , Liu Dan
Published: November 2024

Background

At present, the available evidence regarding the relationship between duration of phenoxybenzamine use and postoperative delirium is inadequate in suspected adrenal pheochromocytoma.

Objective

To understand how changes in the duration of phenoxybenzamine use may affect postoperative delirium. The secondary objective of this study is to explore how the duration of phenoxybenzamine use may jointly influence postoperative delirium together with other interacting variables.

Methods

We conducted a retrospective cohort study involving 527 participants with a preoperative diagnosis of suspected pheochromocytoma. CT characteristics, preoperative preparation, intraoperative infusion, estimated bleeding, use of intraoperative vasoactive drugs, and outcomes were obtained from all participants. Logistic regression and interaction effects were utilized to substantiate the research objectives.

Results

A total of 108 (20.5%) developed postoperative delirium, which was seen in 37 (18.0%) in the pheochromocytoma group and 71 (22.0%) in the non-pheochromocytoma group. The incidence of postoperative delirium showed no statistically significant differences in the two groups. A positive association between the duration of phenoxybenzamine use and the risk of postoperative delirium was observed (OR = 1.05, 95%CI = 1.03–1.08, p < 0.01), independent of confounders. The relationship between the duration of phenoxybenzamine use and postoperative delirium differed according to the presence or absence of pheochromocytoma, suggesting an interactive effect (p < 0.05).

Conclusion

This study highlights the influence of inappropriate duration of phenoxybenzamine use on the risk of incident postoperative delirium, independent of confounders. The effect of duration of phenoxybenzamine use causes a further increase in the risk of postoperative delirium, especially in non-pheochromocytomas.
Revealing the metabolic potential and environmental adaptation of nematophagous fungus, Purpureocillium lilacinum, derived from hadal sediment
Authors: Li Yongqi , Zhang Changhao , Zhong Maosheng , Hu Shenao , Cui Yukun , Fang Jiasong , Yu Xi
Published: November 2024

The extreme environment shapes fungi in deep-sea sediments with novel metabolic capabilities. The ubiquity of fungi in deep-sea habitats supports their significant roles in these ecosystems. However, there is limited research on the metabolic activities and adaptive mechanisms of filamentous fungi in deep-sea ecosystems. In this study, we investigated the biological activities, including antibacterial, antitumor and nematicidal activity of Purpureocillium lilacinum FDZ8Y1, isolated from sediments of the Mariana Trench. A key feature of P. lilacinum FDZ8Y1 was its tolerance to high hydrostatic pressure (HHP), up to 110 MPa. We showed that HHP affected its vegetative growth, development, and production of secondary metabolites, indicating the potential for discovering novel natural products from hadal fungi. Whole-genome sequencing of P. lilacinum FDZ8Y1 revealed the metabolic potential of this piezotolerant fungus in carbon (carbohydrate metabolism), nitrogen (assimilatory nitrate reduction and protein degradation) and sulfur cycling processes (assimilatory sulfate reduction). Transcriptomic analysis under elevated HHP showed that P. lilacinum FDZ8Y1 may activate several metabolic pathways and stress proteins to cope with HHP, including fatty acid metabolism, the antioxidant defense system, the biosynthetic pathway for secondary metabolites, extracellular enzymes and membrane transporters. This study provides valuable insights into the metabolic potential and adaptation mechanisms of hadal fungi to the challenging conditions of the hadal environment.
Comparative study of endophytic bacterial strains from non-host crops for enhancing plant growth and managing early blight in tomato
Authors: Kukreti Aditya , Siddabasappa Chethana Bangi , Krishnareddy Prasannakumar Muthakapalli , Devanna Pramesh , Basavapatna Subbanna Yashavanth , Channappa Manjunatha , Reddy Namburi Karunakar , Hashem Abeer , Alsayed Mashail Fahad , Abd_Allah Elsayed Fathi
Published: November 2024

Bacillus pseudomycoides, Paenibacillus polymyxa, and B. velezensis are potent bacterial endophytes, which typically exhibit host-specific interactions. However, comparative studies of these endophytes in vitro and in planta in non-host crops are lacking. Therefore, in this study, we evaluated the potential of endophytes B. pseudomycoides strain HP3d, P. polymyxa strain PGSS1, B. velezensis strain A6, and P42, isolated from various crop ecosystems in promoting plant growth and inducing systemic resistance against early blight disease in tomato. In vitro, endophytes exhibited 44.44–55.56% and 37.50–87.50% inhibition of Alternaria solani in dual culture and volatilome bioassay, respectively. In the glasshouse, individual and combined applications via seed treatment (ST), seedling dip (SD), and foliar spray (FS) significantly enhanced shoot growth (23.63–57.61%), root growth (43.27–118.23%), number of leaves (77.52–93.58%), number of shoots (33.42–45.28%) and root dry matter (42.17–43.86%), reducing early blight (PDI) by 70.95–76.12% compared to uninoculated control. Enzymatic activities, including such as polyphenol oxidase (30–40 fold), peroxidase (65.00–75.00 fold), superoxide dismutase (34.20–37.20 fold) and phenylalanine ammonia-lyase (44.44–45.56 fold) were elevated post-inoculation in endophytes treated tomato plants challenged with A. solani compared to control treated only with A. solani and declined after the fifth day. The total chlorophyll content declined from the 0th to the 10th day, but endophyte treated plants exhibited lesser reductions (2.03–2.09) than uninoculated control. Field trials confirmed the glasshouse findings, showing reduced early blight and improved growth parameters in tomato where the ST + SD + FS combination emerged as the most effective treatment for all endophytes showing 1.06–1.88 fold increase in fruit yield per plant and 28.92–32.52% decrease in PDI compared to untreated control. Thus, the study highlights the broad-spectrum potential of these strains in promoting plant growth and controlling early blight in tomato, demonstrating non-host specificity. These endophytes offer eco-friendly alternatives to chemical pesticides, supporting sustainable agriculture. Their success in field trials suggests the potential for commercialization and large-scale use across diverse crops and pave the way for further interdisciplinary research to optimize their application in integrated pest management strategies.
Somatosensory integration in robot-assisted motor restoration post-stroke
Authors: Lin Legeng , Qing Wanyi , Zheng Zijian , Poon Waisang , Guo Song , Zhang Shaomin , Hu Xiaoling
Published: November 2024

Disruption of somatosensorimotor integration (SMI) after stroke is a significant obstacle to achieving precise motor restoration. Integrating somatosensory input into motor relearning to reconstruct SMI is critical during stroke rehabilitation. However, current robotic approaches focus primarily on precise control of repetitive movements and rarely effectively engage and modulate somatosensory responses, which impedes motor rehabilitation that relies on SMI. This article discusses how to effectively regulate somatosensory feedback from target muscles through peripheral and central neuromodulatory stimulations based on quantitatively measured somatosensory responses in real time during robot-assisted rehabilitation after stroke. Further development of standardized recording protocols and diagnostic databases of quantitative neuroimaging features in response to post-stroke somatosensory stimulations for real-time precise detection, and optimized combinations of peripheral somatosensory stimulations with robot assistance and central nervous neuromodulation are needed to enhance the recruitment of targeted ascending neuromuscular pathways in robot-assisted training, aiming to achieve precise muscle control and integrated somatosensorimotor functions, thereby improving long-term neurorehabilitation after stroke.
Supplementation with inulin reverses cognitive flexibility alterations and modulates the gut microbiota in high-fat-fed mice
Authors: González-Velázquez Gabriela , Aguirre-Garrido José Félix , Oros-Pantoja Rigoberto , Salinas-Velarde Isidro Daniel , Contreras Irazú , Estrada José Antonio , Soto-Piña Alexandra Estela
Published: November 2024

Introduction

Alterations in cognitive performance are associated with inadequate nutritional states and diet composition. Prebiotics, such as inulin, are substances that can modulate the gut microbiome and, consequently, brain function by producing metabolites such as short-chain fatty acids (SCFAs). This study aimed to evaluate the effect of supplementation with inulin on cognitive flexibility, body composition, and gut microbiota in a murine model exposed to a high-fat (HF) diet.

Methods

CD1 mice were divided into five groups: control fed a standard diet (C), high-fat diet (HF), inulin (I), high-fat diet with inulin (HFI), and manipulation control (M). Dietary supplementation was administered for 6 weeks. Cognitive flexibility was assessed using the Attentional Set-Shifting Test (AST). In addition, body composition was measured via electrical bioimpedance and adipose tissue compartments of each mouse were removed and weighed. Finally, gut microbiota metataxonomic was analyzed through metataxonomic bacterial 16S rRNA sequencing.

Results

We observed that HF group required more AST trials than the C, HFI, and I groups in the compound discrimination (CD) and extra-dimensional (ED) stages. Notably, the HFI group required fewer trials than the HF group in the ED stage (p = 0.0187). No significant differences in overall body composition were observed between the groups. However, the percentage of gonadal and peritoneal adipose tissue was significantly higher in the HF and I groups compared to the C group. Statistically significant differences in alpha diversity for gut microbiota were observed using the Shannon, Simpson, and Chao1 indices. The I group showed a decrease in bacterial diversity compared to the HF group. While no differences were observed between groups in the phyla Bacillota and Bacteroidotes, Clostridium bacteria represented a lower proportion of sequences in the I group compared to the C group. Additionally, Lactobacillus represented a lower proportion of sequences in the HF group compared to the C and I groups.

Discussion

These findings suggest that supplementation with inulin could be a useful approach to mitigate the negative effects of an HF diet on cognitive flexibility and modulate gut microbiota composition.
Intravenous thrombolysis and risk of early-onset post-stroke depression: a propensity score matched cohort study
Authors: Lu Jieyi , Zhang Lulu , Zhang Yi , Mao Huawu , Fang Qi
Published: November 2024

Background

Depression is common in stroke survivors and affects their recovery and quality of life (QoL). Intravenous thrombolysis (IVT) can improve post-stroke outcomes but the impact on early-onset post-stroke depression (PSD) is unclear. This was evaluated by comparing depression symptoms between patients with acute ischemic stroke (AIS) with vs. without IVT.

Methods

This retrospective cohort study included 633 patients with AIS. The 17-item Hamilton Depression Rating Scale was used to evaluate depression in patients 14–21 days after stroke onset. Propensity score matching was used to minimize intervention bias between the two groups.

Results

Of the 633 patients, 120 (19.0%) received IVT and 513 (81%) did not. Before matching, the prevalence of early-onset PSD was lower in the IVT group than in the non-IVT group (18.3% vs. 29.2%, p < 0.05). In the multivariate logistic regression analysis, the risk of early-onset PSD was significantly lower in the IVT group than in the non-IVT group [odds ratio (OR) = 0.48; 95% confidence interval: 0.28–0.83]. The results were stable after adjusting for potential confounders by inverse probability of treatment weighting and using a pairwise algorithm based on propensity scores (ORs between 0.44 and 0.61, all p < 0.05); were robust to unmeasured confounding as assessed by E-value analysis; and were consistent in subgroup analyses.

Conclusion

IVT is associated with a reduced risk of early-onset PSD and can improve the QoL of patients with AIS during post-stroke recovery.
Case report: A novel transcutaneous electrical nerve stimulation improves dysesthesias and motor behaviors after transverse myelitis
Authors: Nishi Yuki , Ikuno Koki , Minamikawa Yuji , Osumi Michihiro , Morioka Shu
Published: November 2024

Purpose

Transverse myelitis (TM)-associated dysesthesia is diverse and frequently resistant to treatment. This study explored the comprehensive effects of a novel transcutaneous electrical nerve stimulation (TENS) approach tailored to an individual’s specific dysesthesia profile in a patient with TM.

Patient and method

A 52-year-old woman with severe dysesthesias in the left C8 sensory area caused by TM underwent an A-B-A-B-A design intervention. The baseline (phase A) and intervention (phase B) phases were both 7 days. Tingling and allodynia were scored on an 11-point numerical rating scale pre-, post-, and 1 h post-treatment. Upper limb activities during daily living were assessed using a wrist-worn accelerometer. The intervention phase consisted of 60-min sessions of TENS two times daily. Furthermore, the intervention and carry-over effects of TENS were evaluated using Tau-U and Bayesian unknown change point models.

Results

The effects of TENS resulted in the immediate improvement in tingling, allodynia, and upper limb activity. Long-term effects of TENS affected tingling and upper limb activity; however, no impacts on allodynia were observed.

Conclusion

This novel TENS approach shows promise as an effective treatment, even in rare and treatment-resistant dysesthesia associated with TM.
Bibliometric and visualized analysis of 2014–2024 publications on therapy for diabetic peripheral neuropathy
Authors: Fu Baitian , Luo Ning , Zeng Yichen , Chen Yutian , Wie Low Je , Fang Jianqiao
Published: November 2024

Background

This research aimed to examine the global developing patterns in the treatment of diabetic peripheral neuropathy (DPN) using a bibliometric analysis of published literature.

Methods

We extracted publication data from papers published between 2014 and 2024 using a specific topic search in the “Web of Science Core Collection” (WoSCC) database. Various metrics, such as the number of papers, citations, authors, countries, institutions, and references, were collected for analysis. To further explore the data, CiteSpace was employed to examine co-citation patterns among authors, identify collaborative efforts between countries and institutions, and uncover emerging trends using burst keywords and reference analysis.

Results

The study encompassed 2,488 publications that exhibited an increasing trend in annual output. Notably, the journal PAIN, the United States, the Pfizer institution, and the author Feldman, EvaL emerged as the most prolific contributors to this research domain. The term “placebo-controlled trial” was the most prominent burst keyword from 2014 to 2017, whereas “spinal cord stimulation” held this distinction in the recent 5-year span. Furthermore, the publication titled “Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis-2015” demonstrated the highest burst in terms of references.

Conclusion

This study is the first to objectively reveal the current hotspots and trends in DPN treatment. The results indicate that drug therapy remains the primary first-line treatment for DPN and that future research on DPN treatment will likely focus on “spinal cord stimulation” and “pain management.” These findings provide valuable insights into DPN treatment.
Cognotoxemia: endotoxemia and gender predict changes in working memory performance in healthy adults
Authors: McDonnell Sally C. , Graham-Engeland Jennifer E. , Sliwinski Martin J. , Engeland Christopher G. , Knight Erik L.
Published: November 2024

Introduction

Examining the contribution of peripheral systems to cognitive function under healthy circumstances may improve our understanding of the systems that confer risk or resilience in diseased states. Endotoxemia—a pro-inflammatory response to the translocation of bacteria that reside in the gut on other sources (e.g., respiratory tract; infection) into the blood—was hypothesized to relate to worsened cognitive functioning. Gender was explored as a moderator.

Methods

A sample of 162 healthy adults (25–65 years old) provided plasma, from which a measure of endotoxemia was determined [i.e., the ratio of lipopolysaccharide binding protein (LBP) to soluble cluster of differentiation 14 receptors (sCD14)]. Participants performed an array of laboratory and ambulatory cognitive tasks at three timepoints, each separated by 9 months. Two sets of multilevel models were used: Prospective models, linking endotoxemia at baseline with changes in cognition across time, and coupling models, which examine correlations of endotoxemia with cognition across time.

Results

A prospective model indicated lower levels of endotoxemia at baseline predicted improvements in working memory across the three timepoints; higher levels were associated with no change in cognitive performance. Gender was not found to modulate this finding. Interestingly, a coupling analysis of endotoxemia and gender across time showed that in men, those with higher endotoxemia performed better at the working memory task overall; in women, working memory performance was similar regardless of endotoxemia level.

Conclusion

This work provides initial evidence that endotoxemia may be associated with a dampening of improvement in working memory, improvement consistent with practice effects, which should be expected in a sample of healthy, relatively young adults. The findings also provide preliminary evidence that, at least for men, higher degrees of endotoxemia are not inherently negative, and may link with short term positive outcomes for working memory.
Exploring the role of Cdk5 on striatal synaptic plasticity in a 3-NP-induced model of early stages of Huntington’s disease
Authors: Hernández-Echeagaray Elizabeth , Miranda-Barrientos Jorge A. , Nieto-Mendoza Elizabeth , Torres-Cruz Francisco Miguel
Published: November 2024

Impaired mitochondrial function has been associated with the onset of neurodegenerative diseases. Specifically, certain mitochondrial toxins, such as 3-nitropropionic acid (3-NP), initiate cellular changes within the striatum that closely resemble the pathology observed in Huntington’s disease (HD). Among the pivotal signaling molecules contributing to neurodegeneration, cyclin-dependent kinase 5 (Cdk5) stands out. In particular, Cdk5 has been implicated not only in cellular pathology but also in the modulation of synaptic plasticity. Given its widespread presence in the striatum, this study seeks to elucidate the potential role of Cdk5 in the induction of corticostriatal synaptic plasticity in murine striatal cells subjected to subchronic doses of 3-NP in vivo, aiming to mimic the early stages of HD. Immunostaining analyses revealed an increase in Cdk5 in tissues from animals treated with 3-NP, without a significant change in protein levels. Regarding striatal plasticity, long-term depression (LTD) was induced in both control and 3-NP cells when recorded in voltage clamp mode. The Cdk5 inhibitor roscovitine-reduced LTD in most cells. A minority subset of cells exhibited long-term potentiation (LTP) generation in the presence of roscovitine. The inhibitor of D1 receptors SCH23390 prevented LTP in three of nine cells, implying that MSN cells lacking D1/PKA activation were capable of LTP induction when Cdk5 was also blocked. Nevertheless, the co-administration of H89, a PKA inhibitor, along with roscovitine, prevented the generation of any type of plasticity in all recorded cells. These findings show the impact of 3-NP treatment on striatal plasticity and suggest that Cdk5 during early neurodegeneration may attenuate signaling pathways that lead neurons to increase their activity.
Can ChatGPT help patients understand radiopharmaceutical extravasations?
Authors: Alvarez Madeleine
Published: November 2024

A previously published paper in the official journal of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) concluded that the artificial intelligence chatbot ChatGPT may offer an adequate substitute for nuclear medicine staff informational counseling to patients in an investigated setting of 18F-FDG PET/CT. To ensure consistency with the previous paper, the author and a team of experts followed a similar methodology and evaluated whether ChatGPT could adequately offer a substitute for nuclear medicine staff informational counseling to patients regarding radiopharmaceutical extravasations. We asked ChatGPT fifteen questions regarding radiopharmaceutical extravasations. Each question or prompt was queried three times. Using the same evaluation criteria as the previously published paper, the ChatGPT responses were evaluated by two nuclear medicine trained physicians and one nuclear medicine physicist for appropriateness and helpfulness. These evaluators found ChatGPT responses to be either highly appropriate or quite appropriate in 100% of questions and very helpful or quite helpful in 93% of questions. The interobserver agreement among the evaluators, assessed using the Intraclass Correlation Coefficient (ICC), was found to be 0.72, indicating good overall agreement. The evaluators also rated the inconsistency across the three ChatGPT responses for each question and found irrelevant or minor inconsistencies in 87% of questions and some differences relevant to main content in the other 13% of the questions. One physician evaluated the quality of the references listed by ChatGPT as the source material it used in generating its responses. The reference check revealed no AI hallucinations. The evaluator concluded that ChatGPT used fully validated references (appropriate, identifiable, and accessible) to generate responses for eleven of the fifteen questions and used generally available medical and ethical guidelines to generate responses for four questions. Based on these results we concluded that ChatGPT may be a reliable resource for patients interested in radiopharmaceutical extravasations. However, these validated and verified ChatGPT responses differed significantly from official positions and public comments regarding radiopharmaceutical extravasations made by the SNMMI and nuclear medicine staff. Since patients are increasingly relying on the internet for information about their medical procedures, the differences need to be addressed.
Decreasing the carbon footprint of food through public procurement—A case study from the municipality of Härnösand
Authors: Kjellberg Mari , Skoglund Wilhelm , Haller Henrik
Published: November 2024

Eating habits are among the strongest drivers of negative environmental impact. Public procurement has been suggested as an efficient lever to catalyze changes within the food system. This study examines alternative purchase processes that may decrease the carbon footprint of publicly procured food through a case study of a municipality in the Northern part of Sweden. The GHG emissions associated with the current food service in the case study were 2.2 kg CO2e per kg food and must be reduced by 40.9% by 2030 to comply with the Paris Agreement; 76% of the emissions derive from food of animal origin (44% from unprocessed red meat). Three alternative diet scenarios, “zero red meat,” “−50% red meat,” and “flexitarian free from red meat,” were explored. Only 6% of the total purchased food kilograms were altered, yet the cutback of meat caused GHG emissions reductions turned out to be as high as 44%. The Swedish Law on Public Procurement, deficient infrastructure, unsustainable food culture, and local politicians' reluctance to change were mentioned as the main obstacles to materializing necessary changes in the food procurement system. The respondents also pointed out essential policy changes at the national and municipal levels.