bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the immune response to Mycobacterium tuberculosis: a comprehensive narrative review and implications in disease relapse
Authors: Rahman Fatima 
Published: November 2024

IntroductionTuberculosis remains the leading cause of death from infectious diseases among adults worldwide. To date, an overarching review of the immune response to Mtb in humans has not been fully elucidated, with innate immunity remaining poorly understood due to historic focus on adaptive immunity. Specifically, there is a major gap concerning the contribution of the immune system to overall bacterial clearance, particularly residual bacteria. This review aims to describe the time course of interactions between the host immune system and Mtb, from the start of the infection to the development of the adaptive response. Concordantly, we aim to crystallize the pathogenic effects and immunoevasive mechanisms of Mtb. The translational value of animal data is also discussed.MethodsThe literature search was conducted in the PubMed, ScienceDirect, and Google Scholar databases, which included reported research from 1990 until 2024. A total of 190 publications were selected and screened, of which 108 were used for abstraction and 86 were used for data extraction. Graphical summaries were created using the narrative information (i.e., recruitment, recognition, and response) to generate clear visual representations of the immune response at the cellular and molecular levels.ResultsThe key cellular players included airway epithelial cells, alveolar epithelial cells, neutrophils, natural killer cells, macrophages, dendritic cells, T cells, and granulomatous lesions; the prominent molecular players included IFN-γ, TNF-α, and IL-10. The paper also sheds light on the immune response to residual bacteria and applications of the data.DiscussionWe provide a comprehensive characterization of the key immune players that are implicated in pulmonary tuberculosis, in line with the organs or compartments in which mycobacteria reside, offering a broad vignette of the immune response to Mtb and how it responds to residual bacteria. Ultimately, the data presented could provide immunological insights to help establish optimized criteria for identifying efficacious treatment regimens and durations for relapse prevention in the modeling and simulation space and wider fields.
Effect of hypoxia-induced mIL15 expression on expansion and memory progenitor stem-like TILs in vitro
Authors: Sun Zhen , Xu Aotian , Wu Zhaojun , Lan Xiaohao , Gao Ganchen , Guo Bin , Yu Zhongjie , Shao Lin , Wu Hao , Lv Min , Wang Yongjie , Zhao Yi , Wang Bin 
Published: November 2024

IntroductionThe adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) has proven clinically beneficial in patients with non-small cell lung cancer refractory to checkpoint blockade immunotherapy, which has prompted interest in TIL-adoptive cell transfer. The transgenic expression of IL15 can promote the expansion, survival, and function of T cells ex vivo and in vivo and enhance their anti-tumor activity. The effect of expressing mIL15 regulated by hypoxia in the tumor microenvironment on the expansion, survival, and stem-like properties of TILs has not been explored.MethodsUsing TILs expanded from the tumor tissues of lung cancer patients, TILs with or without mIL15 expression (TIL-mIL15 or UN-TIL) were generated by lentiviral transduction. To reflect the advantages of mTIL15, the cells were divided into groups with IL2 (TIL-mIL15+IL2) or without IL2 (TIL-mIL15-IL2).ResultsCompared to UN-TIL cells, mIL15 expression had a similar capacity for promoting TIL proliferation and maintaining cell viability. Our experimental findings indicate that, compared to UN-TIL and TIL-mIL15+IL2 cells, the expression of mIL15 in TIL-mIL15-IL2 cells promoted the formation of stem-like TILs (CD8+CD39-CD69-) and led to significant decreases in the proportion and absolute number of terminally differentiated TILs (CD8+CD39+CD69+). RNA-Seq data revealed that in TIL-mIL15-IL2 cells, the expression of genes related to T cell differentiation and effector function, including PRDM1, ID2, EOMES, IFNG, GZMB, and TNF, were significantly decreased, whereas the expression of the memory stem-like T cell marker TCF7 was significantly increased. Furthermore, compared to UN-TIL and TIL-mIL15+IL2 cells, TIL-mIL15-IL2 cells showed significantly lower expression levels of inhibitory receptors LAG3, TIGIT, and TIM3, which was consistent with the RNA-Seq results.DiscussionThis study demonstrates the superior persistence of TIL-mIL15-IL2 cells, which may serve as a novel treatment strategy for lung cancer patients.
TLR7 rs179008 (A/T) and TLR7 rs3853839 (C/G) polymorphisms are associated with variations in IFN-α levels in HTLV-1 infection
Authors: Santana Emmanuelle Giuliana Mendes , Ferreira Fabiane dos Santos , Brito Wandrey Roberto dos Santos , Lopes Felipe Teixeira , de Lima Aline Cecy Rocha , Neto Gabriel dos Santos Pereira , Amoras Ednelza da Silva Graça , Lima Sandra Souza , da Costa Carlos Araujo , Souza Maísa Silva , Ishak Ricardo , Cayres-Vallinoto Izaura Maria Vieira , Vallinoto Antonio Carlos Rosário , Queiroz Maria Alice Freitas 
Published: November 2024

IntroductionTLR7 detects the presence of single-stranded RNA (ssRNA) viruses, including human T-lymphotropic virus 1 (HTLV-1), and triggers antiviral and inflammatory responses that are responsible for infection control. Genetic variations in the TLR7 gene may alter cytokine production and influence the course of HTLV-1 infection. In the present study, the associations of TLR7 gene polymorphisms with HTLV-1-related symptoms, receptor expression levels, IFN-α and TNF-α levels and the proviral load were investigated.MethodsBlood samples from 159 individuals with HTLV-1 infection (66 with inflammatory diseases and 93 asymptomatic individuals) and 159 controls were collected. The genotyping of polymorphisms, TLR7 gene expression analysis and the quantification of the proviral load were performed by real-time PCR, and cytokine measurement was performed by enzyme-linked immunosorbent assay (ELISA).ResultsCarriers of the polymorphic allele for TLR7 rs179008 (A/T) had lower levels of IFN-α, while carriers of the polymorphic allele for TLR7 rs3853839 (C/G) had higher levels of TLR7 and IFN-α expression. The polymorphisms were not associated with symptoms of diseases related to HTLV-1 infection. The combination of A/G alleles for the TLR7 rs179008 (A/T) and TLR7 rs3853839 (C/G) polymorphisms was associated with increased IFN-α levels and a decreased proviral load.DiscussionAlthough the polymorphisms did not influence the presence of symptoms of diseases caused by HTLV-1, carriers of the wild-type alleles for TLR7 rs179008 (A/T) and the polymorphism for TLR7 rs3853839 (C/G) appears to have a stronger antiviral response and increased infection control.
Dynamics of cytokine and antibody responses in community versus hospital SARS-CoV-2 infections
Authors: Singh Tulika , Macintyre Andrew N. , Burke Thomas W. , Anderson Jack , Petzold Elizabeth , Stover Erica L. , French Matthew J. , Oguin Thomas H. , Demarco Todd , McClain Micah T. , Ko Emily R. , Park Lawrence P. , Denny Thomas , Sempowski Gregory D. , Woods Christopher W. 
Published: November 2024

IntroductionDysregulated host cytokine responses to SARS-CoV-2 infection are a primary cause of progression to severe disease, whereas early neutralizing antibody responses are considered protective. However, there are gaps in understanding the early temporal dynamics of these immune responses, and the profile of productive immune responses generated by non-hospitalized people with mild infections in the community.MethodsHere we conducted a prospective cohort study of people with suspected infections/exposures in the US state of North Carolina, before vaccine availability. We recruited participants not only in hospitals/clinics, but also in their homes. With serial sampling, we compared virologic and immunologic factors in 258 community cases versus 114 hospital cases of COVID-19 to define factors associated with severity.ResultsWe found that high early neutralizing antibodies were associated with lower nasal viral load, but not protection from hospitalization. Cytokine responses were evaluated in 125 cases, with subsets at first versus second week of illness to assess for time-dependent trajectories. The hospital group demonstrated a higher magnitude of serum IL-6, IL-1R antagonist, IP-10, and MIG; prolonged upregulation of IL-17; and lesser downregulation of GROα, IL-1R antagonist, and MCP1, in comparison to the community group suggesting that these factors may contribute to immunopathology. In the second week of illness, 2-fold increases in IL-6, IL-1R antagonist, and IP-10 were associated with 2.2, 1.8, and 10-fold higher odds of hospitalization respectively, whereas a 2-fold increase in IL-10 was associated with 63% reduction in odds of hospitalization (p&lt;0.05). Moreover, antibody responses at 3-6 months post mild SARS-CoV-2 infections in the community revealed long-lasting antiviral IgM and IgA antibodies as well as a stable set point of neutralizing antibodies that were not waning.DiscussionOur data provide valuable temporal cytokine benchmarks to track the progression of immunopathology in COVID-19 patients and guide improvements in immunotherapies.
Prediction of acute myeloid leukemia prognosis based on autophagy features and characterization of its immune microenvironment
Authors: Zhu Chaoqun , Feng Xiangyan , Tong Lanxin , Mu Peizheng , Wang Fei , Quan Wei , Dong Yucui , Zhu Xiao 
Published: November 2024

BackgroundAutophagy promotes the survival of acute myeloid leukemia (AML) cells by removing damaged organelles and proteins and protecting them from stress-induced apoptosis. Although many studies have identified candidate autophagy genes associated with AML prognosis, there are still great challenges in predicting the survival prognosis of AML patients. Therefore, it is necessary to identify more novel autophagy gene markers to improve the prognosis of AML by utilizing information at the molecular level.MethodsIn this study, the Random Forest, SVM and XGBoost algorithms were utilized to identify autophagy genes linked to prognosis, respectively. Subsequently, six autophagy genes (TSC2, CALCOCO2, BAG3, UBQLN4, ULK1 and DAPK1) that were significantly associated with patients’ overall survival (OS) were identified using Lasso-Cox regression analysis. A prediction model incorporating these autophagy genes was then developed. In addition, the immunological microenvironment analysis of autophagy genes was performed in this study. ResultsThe experimental results showed that the predictive model had good predictive ability. After adjusting for clinicopathologic parameters, this feature proved an independent prognostic predictor and was validated in an external AML sample set. Analysis of differentially expressed genes in patients in the high-risk and low-risk groups showed that these genes were enriched in immune-related pathways such as humoral immune response, T cell differentiation in thymus and lymphocyte differentiation. Then immune infiltration analysis of autophagy genes in patients showed that the cellular abundance of T cells CD4+ memory activated, NK cells activated and T cells CD4+ in the high-risk group was significantly lower than that in the low-risk group.ConclusionThis study systematically analyzed autophagy-related genes (ARGs) and developed prognostic predictors related to OS for patients with AML, thus more accurately assessing the prognosis of AML patients. This not only helps to improve the prognostic assessment and therapeutic outcome of patients, but may also provide new help for future research and clinical applications.
Compost mediates the recruitment of core bacterial communities in alfalfa roots to enhance their productivity potential in saline-sodic soils
Authors: Wei Tian-Jiao , Li Guang , Cui Yan-Ru , Xie Jiao , Teng Xing , Wang Yan-Jing , Li Zhong-He , Guan Fa-Chun , Liang Zheng-Wei 
Published: November 2024

IntroductionComposting is one of the effective environmental protection and sustainable measures for improving soil quality and increasing crop yield. However, due to the special physical and chemical properties of saline-sodic soil and the complex rhizosphere microecological environment, the potential mechanism of regulating plant growth after applying compost in saline-sodic soil remains elusive.MethodsHere, we investigated the effects of different compost addition rates (0, 5, 15, 25%) on plant growth traits, soil chemical properties, and rhizosphere bacterial community structure.ResultsThe results showed that compost promoted the accumulation of plant biomass and root growth, increased soil nutrients, and enhanced the diversity and complexity of the rhizosphere bacterial communities. Moreover, the enriched core bacterial ASVs (Amplicon Sequence Variants) in compost treatment could be reshaped, mainly including dominant genera, such as Pseudomonas, Devosia, Novosphingobium, Flavobacterium, and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium. The functions of these ASVs were energy resources and nitrogen cycle functions, suggesting the roles of these ASVs in improving plant root nutrient resource acquisition for alfalfa growth. The contents of available potassium, available phosphorus, total nitrogen, and organic carbon of the soil surrounding the roots, the root length, root surface area, root volume, and root tips affected the abundance of the core bacterial ASVs, and the soil chemical properties contributed more to the effect of plant biomass.DiscussionOverall, our study strengthens the understanding of the potentially important taxa structure and function of plant rhizosphere bacteria communities, and provides an important reference for developing agricultural microbiome engineering techniques to improve root nutrient uptake and increase plant productivity in saline-sodic soils.
Higher soluble TREM-1 levels are associated with cognitive impairment after acute ischemic stroke
Authors: Chen Zhuo , Yi Xin , Fu Wei , Wu Yong , Zhong Xingju , Fan Chaoli , Jiang Yu , Zhou Qi , Peng Jie , Liao Jieyu , You Zhike , Tan Jingyu 
Published: November 2024

Background and purposeTriggering receptor expressed on myeloid cells-1 (TREM-1) was reported to be critical for mediating the neurological function after stroke, while the impact of soluble TREM-1 (sTREM-1) on cognitive impairment after ischemic stroke is unclear. We aimed to explore the association between sTREM-1 and post-stroke cognitive impairment (PSCI).MethodsWe prospectively recruited consecutive ischemic stroke patients who admitted hospital within 7 days of onset. Serum sTREM-1 concentrations were measured after admission. Cognitive function was assessed at 90 days follow-up using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). PSCI was defined as a MMSE score of &lt;27 or a MoCA score &lt; 26.ResultsA total of 291 patients (mean age, 66.6 years; 46.0% female) were enrolled for this study. Among these participants, the median sTREM-1 concentrations were 289.4 pg/mL. According to the MoCA score, 153 (52.6%) patients experienced PSCI at 3 months. After adjustment for confounding risk factors by multivariate regression analysis, patients with sTREM-1 levels in the fourth quartile were more likely to have increased risk 3-month PSCI (as compared with the first quartile, odds ratio 12.22, 95% confidence intervals, 5.20–28.71, P = 0.001). Restricted cubic spline further confirmed a dose-dependent relationship between sTREM-1 levels and PSCI (P = 0.003 for linearity). Similar significant findings were observed when the cognitive impairment was diagnosed according to the MMSE criterion.ConclusionOur study revealed that higher serum sTREM-1 levels at admission were associated with increased risk of 3-month PSCI.
Prognostic value of thrombocytopenia during hospitalizations in intracerebral hemorrhage patients
Authors: Feng Hao , Luo Xiaoquan , Fu Anhui , Wang Ruoran , Qiao Fei 
Published: November 2024

BackgroundThe thrombocytopenia influences prognoses of critically ill patients. There are few studies exploring the prognostic value of thrombocytopenia among ICH patients. We perform this study to explore the correlation between thrombocytopenia at different timepoints of hospitalizations and mortality of ICH.MethodsICH patients recorded in the Medical Information Mart for Intensive Care-III were selected for this observational study. The thrombocytopenia, defined as platelet &lt;150 × 109/L, was divided into three categories: baseline thrombocytopenia (thrombocytopenia occurred at admission), acquired thrombocytopenia (thrombocytopenia developed since the second day after admission), multiple thrombocytopenia (baseline thrombocytopenia + acquired thrombocytopenia). The main outcome in this study was the 30-day mortality of ICH patients. The univariate and multivariate logistic regression was sequentially performed to discover risk factors of mortality and confirm the correlation between thrombocytopenia groups and mortality of ICH.Results66.5% of 902 ICH patients did not experience the thrombocytopenia since admission. 2.2, 14.5 and 16.7% ICH patients showed the baseline thrombocytopenia, acquired thrombocytopenia initial and multiple thrombocytopenia, respectively. The GCS did not show significant difference between thrombocytopenia groups (p = 0.118). The multiple thrombocytopenia group had the highest incidence of mechanical ventilation (p = 0.041), mortality (p &lt; 0.001), and the longest length of ICU stay (p &lt; 0.001), length of hospital stay (p &lt; 0.001). The multivariate logistic regression found age (p &lt; 0.001), GCS (p &lt; 0.001), glucose (p = 0.013), mechanical ventilation (p = 0.002) was correlated with the mortality of ICH patients. Only the multiple thrombocytopenia group showed significant influence on the mortality of ICH (p = 0.002) in the multivariate logistic regression.ConclusionSingle initial thrombocytopenia at admission dose not influence the mortality of ICH patients. ICH patients experiencing both initial thrombocytopenia and acquired thrombocytopenia have significantly higher mortality risk. The blood platelet level of ICH patients should be monitored continuously during hospitalizations to detect the thrombocytopenia and identify the high risk of poor prognosis.
Italian standardization of the BPSD-SINDEM scale for the assessment of neuropsychiatric symptoms in persons with dementia
Authors: Pozzi Federico Emanuele , D'Antonio Fabrizia , Zuffi Marta , Pelati Oriana , Vernè Davide , Panigutti Massimiliano , Alberoni Margherita , Di Maggio Maria Grazia , Costa Alfredo ,   Sindem BPSD Study Group, Tremolizzo Lucio , Farina Elisabetta 
Published: November 2024

IntroductionBehavioral and Psychological Symptoms of Dementia (BPSD) are a heterogeneous set of psychological reactions and abnormal behaviors in people with dementia (PwD). Current assessment tools, like the Neuropsychiatric Inventory (NPI), only rely on caregiver assessment of BPSD and are therefore prone to bias.Materials and methodsA multidisciplinary team developed the BPSD-SINDEM scale as a three-part instrument, with two questionnaires administered to the caregiver (evaluating BPSD extent and caregiver distress) and a clinician-rated observational scale. This first instrument was tested on a sample of 33 dyads of PwD and their caregivers, and the results were qualitatively appraised in order to revise the tool through a modified Delphi method. During this phase, the wording of the questions was slightly changed, and the distress scale was changed into a coping scale based on the high correlation between extent and distress (r = 0.94). The final version consisted of three 17-item subscales, evaluating BPSD extent and caregiver coping, and the unchanged clinician-rated observational scale.ResultsThis tool was quantitatively validated in a sample of 208 dyads. It demonstrated good concurrent validity, with the extent subscale correlating positively with NPI scores (r = 0.64, p &lt; 0.001) and the coping subscale inversely correlating with NPI distress (r = −0.20, p = 0.004). Diagnosis (Lewy body dementia and frontotemporal dementia), medication (antidepressants and antipsychotics), caregiver, and PwD age predicted BPSD burden on the BPSD-SINDEM scale. Caregiver coping was influenced by diagnosis (Alzheimer’s and Lewy body dementia) and benzodiazepine.DiscussionThe BPSD-SINDEM scale offers a more comprehensive approach compared to NPI, by combining caregiver ratings with clinician observations. The design of the scale allows for rapid administration in diverse clinical contexts, with the potential to enhance the understanding and management of BPSD.
Evaluation of motor fluctuations in Parkinson’s disease: electronic vs. conventional paper diaries
Authors: Asai Kanako , Kawahara Sayo , Shirahata Emi , Iwasaki Kimihiro , Nakai Hikoichiro , Kajiyama Yuta , Taniguchi Seira , Ge Lindun , Kakuda Keita , Kimura Yasuyoshi , Miyahara Tadashi , Ueda Hiroki R. , Ikenaka Kensuke , Mochizuki Hideki 
Published: November 2024

BackgroundPaper symptom diaries are a common tool for assessing motor fluctuations in Parkinson’s disease (PD) patients, but there are concerns about inaccuracies in the assessment of motor fluctuation due to recall bias and poor compliance. We, therefore, developed an electronic diary with reminder and real-time recording functions.Objectives and methodsTo evaluate the effectiveness of the electronic diary, we compared compliance and motor fluctuation assessment with a paper diary. Nineteen PD patients were recruited and recorded paper diaries every 30 min from 8 am to 8 pm for 7 days, followed by 7 days of electronic diary recording using a smartphone and smartwatch. Prior to the recording period, the Parkinson’s Disease Questionnaire (PDQ)-39 and the Movement Disorders Society-sponsored Unified Parkinson’s Disease Rating Scale-Revised (MDS-UPDRS) 1, 2, 3, 4 were measured. Patients completed a patient questionnaire on the usability of the diaries after the recording period.ResultsTotal reported time was significantly longer in paper diaries, but there was no significant difference in the number of entries (paper 115 [71–147] vs. electronic 109 [93–116], p = 0.77). There was a significant correlation between paper and electronic diaries with respect to motor status. ON time rate recorded in the electronic diary was significantly correlated with PDQ-39, MDS-UPDRS 1, 2, and 4, while MDS-UPDRS 1 was only correlated with ON time rate in the paper diary. The usability of our electronic diary was found to be satisfactory based on the results of patient questionnaire.ConclusionElectronic diaries are useful tools that more accurately reflect PD motor fluctuations.