bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA sequencing reveals Immune Education promotes T cell survival in mice subjected to the cecal ligation and puncture sepsis model
Authors: Ham Steven D. , Abraham Mabel N. , Deutschman Clifford S. , Taylor Matthew D. 
Published: March 2024

BackgroundIndividual T cell responses vary significantly based on the microenvironment present at the time of immune response and on prior induced T cell memory. While the cecal ligation and puncture (CLP) model is the most commonly used murine sepsis model, the contribution of diverse T cell responses has not been explored. We defined T cell subset responses to CLP using single-cell RNA sequencing and examined the effects of prior induced T cell memory (Immune Education) on these responses. We hypothesized that Immune Education prior to CLP would alter T cell responses at the single cell level at a single, early post-CLP time point.MethodsSplenic T cells were isolated from C57BL/6 mice. Four cohorts were studied: Control, Immune-Educated, CLP, and Immune-Educated CLP. At age 8 weeks, Immune-Educated and Immune-Educated CLP mice received anti-CD3ϵ antibody; Control and CLP mice were administered an isotype control. CLP (two punctures with a 22-gauge needle) was performed at 12-13 weeks of life. Mice were sacrificed at baseline or 24-hours post-CLP. Unsupervised clustering of the transcriptome library identified six distinct T cell subsets: quiescent naïve CD4+, primed naïve CD4+, memory CD4+, naïve CD8+, activated CD8+, and CD8+ cytotoxic T cell subsets. T cell subset specific gene set enrichment analysis and Hurdle analysis for differentially expressed genes (DEGs) were performed.ResultsT cell responses to CLP were not uniform – subsets of activated and suppressed T cells were identified. Immune Education augmented specific T cell subsets and led to genomic signatures favoring T cell survival in unoperated and CLP mice. Additionally, the combination of Immune Education and CLP effected the expression of genes related to T cell activity in ways that differed from CLP alone. Validating our finding that IL7R pathway markers were upregulated in Immune-Educated CLP mice, we found that Immune Education increased T cell surface IL7R expression in post-CLP mice.ConclusionImmune Education enhanced the expression of genes associated with T cell survival in unoperated and CLP mice. Induction of memory T cell compartments via Immune Education combined with CLP may increase the model’s concordance to human sepsis.
Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme
Authors: Zemtsovski Jan D. , Tumpara Srinu , Schmidt Sonja , Vijayan Vijith , Klos Andreas , Laudeley Robert , Held Julia , Immenschuh Stephan , Wurm Florian M. , Welte Tobias , Haller Hermann , Janciauskiene Sabina , Shushakova Nelli 
Published: March 2024

BackgroundExcessive inflammation, hemolysis, and accumulation of labile heme play an essential role in the pathophysiology of multi-organ dysfunction syndrome (MODS) in sepsis. Alpha1-antitrypsin (AAT), an acute phase protein with heme binding capacity, is one of the essential modulators of host responses to inflammation. In this study, we evaluate the putative protective effect of AAT against MODS and mortality in a mouse model of polymicrobial abdominal sepsis.MethodsPolymicrobial abdominal sepsis was induced in C57BL/6N mice by cecal ligation and puncture (CLP). Immediately after CLP surgery, mice were treated intraperitoneally with three different forms of human AAT—plasma-derived native (nAAT), oxidized nAAT (oxAAT), or recombinant AAT (recAAT)—or were injected with vehicle. Sham-operated mice served as controls. Mouse survival, bacterial load, kidney and liver function, immune cell profiles, cytokines/chemokines, and free (labile) heme levels were assessed. In parallel, in vitro experiments were carried out with resident peritoneal macrophages (MPMΦ) and mouse peritoneal mesothelial cells (MPMC).ResultsAll AAT preparations used reduced mortality in septic mice. Treatment with AAT significantly reduced plasma lactate dehydrogenase and s-creatinine levels, vascular leakage, and systemic inflammation. Specifically, AAT reduced intraperitoneal accumulation of free heme, production of cytokines/chemokines, and neutrophil infiltration into the peritoneal cavity compared to septic mice not treated with AAT. In vitro experiments performed using MPMC and primary MPMΦ confirmed that AAT not only significantly decreases lipopolysaccharide (LPS)-induced pro-inflammatory cell activation but also prevents the enhancement of cellular responses to LPS by free heme. In addition, AAT inhibits cell death caused by free heme in vitro.ConclusionData from the septic CLP mouse model suggest that intraperitoneal AAT treatment alone is sufficient to improve sepsis-associated organ dysfunctions, preserve endothelial barrier function, and reduce mortality, likely by preventing hyper-inflammatory responses and by neutralizing free heme.
Comparative transcriptomics and proteomics analysis of the symbiotic germination of Paphiopedilum barbigerum with Epulorhiza sp. FQXY019
Authors: Tian Fan , Wang Juncai , Ding Fangjun , Wang Lianhui , Yang Yanbing , Bai Xinxiang , Tan Chengjiang , Liao Xiaofeng 
Published: March 2024

IntroductionPaphiopedilum barbigerum is currently the rarest and most endangered species of orchids in China and has significant ornamental value. The mature seeds of P. barbigerum are difficult to germinate owing to the absence of an endosperm and are highly dependent on mycorrhizal fungi for germination and subsequent development. However, little is known about the regulation mechanisms of symbiosis and symbiotic germination of P. barbigerum seeds.MethodsHerein, transcriptomics and proteomics were used to explore the changes in the P. barbigerum seeds after inoculation with (FQXY019 treatment group) or without (control group) Epulorhiza sp. FQXY019 at 90 days after germination.ResultsTranscriptome sequencing revealed that a total of 10,961 differentially expressed genes (DEGs; 2,599 upregulated and 8,402 downregulated) were identified in the control and FQXY019 treatment groups. These DEGs were mainly involved in carbohydrate, fatty acid, and amino acid metabolism. Furthermore, the expression levels of candidate DEGs related to nodulin, Ca2+ signaling, and plant lectins were significantly affected in P. barbigerum in the FQXY019 treatment groups. Subsequently, tandem mass tag-based quantitative proteomics was performed to recognize the differentially expressed proteins (DEPs), and a total of 537 DEPs (220 upregulated and 317 downregulated) were identified that were enriched in processes including photosynthesis, photosynthesis-antenna proteins, and fatty acid biosynthesis and metabolism.DiscussionThis study provides novel insight on the mechanisms underlying the in vitro seed germination and protocorm development of P. barbigerum by using a compatible fungal symbiont and will benefit the reintroduction and mycorrhizal symbiotic germination of endangered orchids.
Spectral exponent assessment and neurofilament light chain: a comprehensive approach to describe recovery patterns in stroke
Authors: Lanzone Jacopo , Zulueta Aida , Boscarino Marilisa , Gallotta Matteo , Argentieri Maria Rosaria , Viganò Alessandro , Sarasso Simone , Colombo Michele A. , D’Ambrosio Sasha , Lunetta Christian , Parati Eugenio 
Published: March 2024

IntroductionUnderstanding the residual recovery potential in stroke patients is crucial for tailoring effective neurorehabilitation programs. We propose using EEG and plasmatic Neurofilament light chain (NfL) levels as a model to depict longitudinal patterns of stroke recovery.MethodsWe enrolled 13 patients (4 female, mean age 74.7 ± 8.8) who underwent stroke in the previous month and were hospitalized for 2-months rehabilitation. Patients underwent blood withdrawal, clinical evaluation and high-definition EEG at T1 (first week of rehabilitation) and at T2 (53 ± 10 days after). We assessed the levels of NfL and we analyzed the EEG signal extracting Spectral Exponent (SE) values. We compared our variables between the two timepoint and between cortical and non-cortical strokes.ResultsWe found a significant difference in the symmetry of SE values between cortical and non-cortical stroke at both T1 (p = 0.005) and T2 (p = 0.01). SE in the affected hemisphere showed significantly steeper values at T1 when compared with T2 (p = 0.001). EEG measures were consistently related to clinical scores, while NfL at T1 was related to the volume of ischemic lesions (r = 0.75; p = 0.003). Additionally, the combined use of NfL and SE indicated varying trends in longitudinal clinical recovery.ConclusionWe present proof of concept of a promising approach for the characterization of different recovery patterns in stroke patients.
Greater white matter degeneration and lower structural connectivity in non-amnestic vs. amnestic Alzheimer’s disease
Authors: Phillips Jeffrey S. , Adluru Nagesh , Chung Moo K. , Radhakrishnan Hamsanandini , Olm Christopher A. , Cook Philip A. , Gee James C. , Cousins Katheryn A. Q. , Arezoumandan Sanaz , Wolk David A. , McMillan Corey T. , Grossman Murray , Irwin David J. 
Published: March 2024

IntroductionMultimodal evidence indicates Alzheimer’s disease (AD) is characterized by early white matter (WM) changes that precede overt cognitive impairment. WM changes have overwhelmingly been investigated in typical, amnestic mild cognitive impairment and AD; fewer studies have addressed WM change in atypical, non-amnestic syndromes. We hypothesized each non-amnestic AD syndrome would exhibit WM differences from amnestic and other non-amnestic syndromes.Materials and methodsParticipants included 45 cognitively normal (CN) individuals; 41 amnestic AD patients; and 67 patients with non-amnestic AD syndromes including logopenic-variant primary progressive aphasia (lvPPA, n = 32), posterior cortical atrophy (PCA, n = 17), behavioral variant AD (bvAD, n = 10), and corticobasal syndrome (CBS, n = 8). All had T1-weighted MRI and 30-direction diffusion-weighted imaging (DWI). We performed whole-brain deterministic tractography between 148 cortical and subcortical regions; connection strength was quantified by tractwise mean generalized fractional anisotropy. Regression models assessed effects of group and phenotype as well as associations with grey matter volume. Topological analyses assessed differences in persistent homology (numbers of graph components and cycles). Additionally, we tested associations of topological metrics with global cognition, disease duration, and DWI microstructural metrics.ResultsBoth amnestic and non-amnestic patients exhibited lower WM connection strength than CN participants in corpus callosum, cingulum, and inferior and superior longitudinal fasciculi. Overall, non-amnestic patients had more WM disease than amnestic patients. LvPPA patients had left-lateralized WM degeneration; PCA patients had reductions in connections to bilateral posterior parietal, occipital, and temporal areas. Topological analysis showed the non-amnestic but not the amnestic group had more connected components than controls, indicating persistently lower connectivity. Longer disease duration and cognitive impairment were associated with more connected components and fewer cycles in individuals’ brain graphs.DiscussionWe have previously reported syndromic differences in GM degeneration and tau accumulation between AD syndromes; here we find corresponding differences in WM tracts connecting syndrome-specific epicenters. Determining the reasons for selective WM degeneration in non-amnestic AD is a research priority that will require integration of knowledge from neuroimaging, biomarker, autopsy, and functional genetic studies. Furthermore, longitudinal studies to determine the chronology of WM vs. GM degeneration will be key to assessing evidence for WM-mediated tau spread.
Effects of hyperbaric oxygen therapy on autistic behaviors and GRIN2B gene expression in valproic acid-exposed rats
Authors: Mohtaj Khorassani Yalda , Moghimi Ali , Khakzad Mohammad Reza , Fereidoni Masoud , Hassani Delaram , Torbati Gah Javad 
Published: March 2024

IntroductionAutism is a complex neurodevelopmental condition characterized by deficits in social interaction, communication, and restricted repetitive behaviors. Hyperbaric oxygen therapy (HBOT) has emerged as a potential treatment for autism, although its effects on behavior and gene expression are not well understood. The GRIN2B gene, known for its involvement in encoding a glutamate receptor subunit crucial for neuron communication and associated with autism, was a focus of this study.MethodsUsing a rat model induced by prenatal exposure to valproic acid, we examined the impact of HBOT on autism-like behaviors and GRIN2B gene expression. Male Wistar rats were categorized into four groups: control, VPA (valproic acid-exposed), VPA+HBOT [2 atmosphere absolute (ATA)], and VPA+HBOT (2.5 ATA). The rats underwent several behavioral tests to assess social behavior, anxiety, stereotype and exploratory behaviors, and learning. Following the behavioral tests, the HBOT groups received 15 sessions of HBOT at pressures of 2 and 2.5 (ATA), and their behaviors were re-evaluated. Subsequently, real-time PCR was employed to measure GRIN2B gene expression in the frontal lobe.ResultsOur results indicated that HBOT significantly increased social interaction and exploratory behaviors in VPA-exposed rats, alongside elevated GRIN2B gene expression in their frontal lobe.DiscussionOur findings imply that HBOT might have a potential role in ameliorating autism-related behaviors in the VPA rat model of autism through potential modulation of GRIN2B gene expression. However, additional research is essential to fully comprehend the underlying mechanisms and refine the HBOT protocol for optimizing its effectiveness in improving autism-related symptoms.
Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study
Authors: Shi Chao , Chen Jie , He Siying , Zhang Yingying , Zhang Yanyue , Yu Lisha 
Published: March 2024

BackgroundMultiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism.MethodsTo investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis (n = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran’s Q statistics were utilized to gauge the heterogeneity of the instrumental variables.ResultsThe results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74–0.95, p = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01–1.36, p = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88–0.99, p = 0.02), Holdemania (OR = 0.89, 95% CI 0.81–0.99, p = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02–1.26, p = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01–1.41, p = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84–0.99, p = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy.ConclusionThe findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms.
Association of multiple serum minerals and vitamins with metabolic dysfunction-associated fatty liver disease in US adults: National Health and Nutrition Examination Survey 2017–2018
Authors: Guo Peisen , Yu Jiahui 
Published: March 2024

BackgroundDespite the rapid increase in the global prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), there are no approved therapeutic drugs for MAFLD yet. Nutrient supplementation might mitigate the risk of MAFLD. It is more typical for individuals to consume multiple nutrients simultaneously. However, the studies exploring the combined effects of multiple nutrients on MAFLD are limited. This study aimed to investigate the relationship between both individual nutrients and their combined influence on the risk of MAFLD.MethodsData were obtained from National Health and Nutrition Examination Survey (NHANES), and 18 types of nutrients were considered in this study. Logistic regression analysis was performed to evaluate the correlation between single nutrients and the risk of MAFLD. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to pinpoint the most relevant nutrient associated with the risk of MAFLD. Subsequently, both Weighted Quantile Sum (WQS) regression and Quantile g-computation (Qgcomp) were used to assess the combined effects of multiple nutrients on the risk of MAFLD.ResultsA total of 3,069 participants were included in this study. LASSO regression analysis showed that Se, α-tocopherol, and γ-tocopherol exhibited a positive association with the risk of MAFLD. In contrast, the serum levels of Co, P, α-cryptoxanthin, LZ, and trans-β-carotene were inversely associated with the prevalence of MAFLD. When Se and two types of vitamin E were excluded, the WQS index showed a significant inverse relationship between the remaining 15 nutrients and the risk of MAFLD; α-cryptoxanthin showed the most substantial contribution. Similarly, Qgcomp suggested that the combined effects of these 15 nutrients were associated with a lower risk of MAFLD, with α-cryptoxanthin possessing the most significant negative weights.ConclusionThis study suggested that the complex nutrients with either a low proportion of Se, α-tocopherol, and γ-tocopherol or without them should be recommended for patients with MAFLD to reduce its risk.
The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia
Authors: Muhammad Muhammad , Saifo Maher , Aljamali Majd , Alali Mousa , Ghanem Khaled M. 
Published: March 2024

IntroductionPolymorphisms in NUDT15 may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the NUDT15 (c.415C&gt;T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL).MethodsThis is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The NUDT15 genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated.ResultsA total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with NUDT15 (c.415C&gt;T; rs116855232) CT genotype, and 1 patient (1.08%) with NUDT15 TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (P=0.009). Early onset leukopenia was significantly associated with the NUDT15 polymorphism (OR: 6.16, 95% CI: 1.11-34.18, P=0.037). There was no association between the NUDT15 genotype and hepatotoxicity.ConclusionApproximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in NUDT15 rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the NUDT15 genotype in pediatric patients with ALL.
Assessment of knowledge and perceptions of human papillomavirus vaccine and its determinants among women who have eligible daughters in Debre Berhan City, Ethiopia: a cross-sectional study
Authors: Tsige Abate Wondesen , Ayenew Kassahun Dires , Ayele Siraye Genzeb 
Published: March 2024

IntroductionGlobally, cervical cancer(CC) is the second most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women. Human papillomavirus (HPV) infection is the leading cause of CC. Persistent infection with HPV accounts for 90% of all CC cases. The human papillomavirus vaccine has the great potential to prevent HPV-related infections for millions of women and men. The current study aimed to assess knowledge and perceptions towards the HPV vaccine and its determinants among women who have eligible daughters in Debre Berhan City, Ethiopia.MethodsA cross-sectional study was conducted from April 2, 2023, to May 15, 2023. A multistage sampling procedure was used to recruit 607 women participants. Descriptive statistics were used to summarize socio-demographic data. Univariable and multivariable binary logistic regression analyses were performed to measure the associations between the dependent and independent variables. A p-value of &lt;0.05 was considered statistically significant.ResultsMore than three-fourths of the participants, 479 individuals (80%) were currently married, and 243(40.1%) had a diploma or higher education level. Of 456(75.12) participants reported, they had information about cervical cancer. For 449(73.9%) of the participants, television was the main evidence. The majority of 352(59.99%) participants knew the HPV vaccine could be offered to a female child aged 9-14 years old. Only 215(35.4%) participants think the HPV vaccine was safe and effective. Women who had a degree and above educational level were about 9 times more likely to have good knowledge about the HPV vaccine than study participants who did not read and write (AOR=9.21; 95% CI=2.82-12.16; p=0.004). Women who did not have information about the HPV vaccine before this study were about 80% less likely to have a positive perception of the HPV vaccine than participants who had earlier information about the HPV vaccine (AOR=0.8; 95%CI=0.63-0.49; P=003).ConclusionWomen had poor knowledge and perceptions about the HPV vaccine. Maternal marital status, age, and having information about the HPV vaccine were the only predictors of women’s knowledge of the HPV vaccine.