bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum metabolomic profiles in BALB/c mice induced by Babesia microti infection
Authors: Shen Liang , Wang Chunhua , Wang Ruilin , Hu Xue , Liao Shiying , Liu Wentong , Du Aoling , Ji Shengwei , Galon Eloiza May , Li Hang , Xuan Xuenan , Xiao Juan , Liu Mingming 
Published: April 2023

IntroductionThe protozoan parasite Babesia microti is the primary cause of human babesiosis. This parasite invades and multiplies inside red blood cells (RBCs), and infections differ significantly based on the age and immune competency of the host. The aim of this study was to investigate the use of serum metabolic profiling to identify systemic metabolic variations between B. microti-infected mice and noninfected controls.MethodsA serum metabolomics analysis of BALB/c mice that had been intraperitoneally injected with 107B. microti-infected RBCs was performed. Serum samples from the early infected group (2 days postinfection), the acutely infected group (9 days postinfection), and the noninfected group were collected and evaluated using a liquid chromatography−mass spectrometry (LC−MS) platform. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) identified metabolomic profiles that differentiated the B. microti-infected and noninfected groups.ResultsOur results confirm that the serum metabolome is significantly influenced by acute B. microti infection and show that infection results in dysregulation of metabolic pathways and perturbation of metabolites. Acutely infected mice displayed perturbations in metabolites associated with taurine and hypotaurine metabolism, histidine metabolism, and arachidonic acid metabolism. Taurocholic acid, anserine, and arachidonic acid may be potential candidates as serological biomarkers for diagnosing B. microti infection at the acute stage. These metabolites could be further examined for their role in disease complexity.DiscussionOur findings demonstrate that the acute stage of B. microti infection induces abnormalities in the metabolites present in mouse serum and provide new insight into the mechanisms involved in systemic metabolic changes that occur during B. microti infection.
Characterization of post-vaccination SARS-CoV-2 T cell subtypes in patients with different hematologic malignancies and treatments
Authors: Pfannes Roald , Pierzchalski Arkadiusz , Maddalon Ambra , Simion Alexandra , Zouboulis Christos C. , Behre Gerhard , Zenclussen Ana Claudia , Westphal Sabine , Fest Stefan , Herberth Gunda 
Published: April 2023

BackgroundTo evaluate the benefits of SARS-CoV-2 vaccination in cancer patients it is relevant to understand the adaptive immune response elicited after vaccination. Patients affected by hematologic malignancies are frequently immune-compromised and show a decreased seroconversion rate compared to other cancer patients or controls. Therefore, vaccine-induced cellular immune responses in these patients might have an important protective role and need a detailed evaluation.MethodsCertain T cell subtypes (CD4, CD8, Tfh, γδT), including cell functionality as indicated by cytokine secretion (IFN, TNF) and expression of activation markers (CD69, CD154) were assessed via multi-parameter flow cytometry in hematologic malignancy patients (N=12) and healthy controls (N=12) after a second SARS-CoV-2 vaccine dose. The PBMC of post-vaccination samples were stimulated with a spike-peptide pool (S-Peptides) of SARS-CoV-2, with CD3/CD28, with a pool of peptides from the cytomegalovirus, Epstein-Barr virus and influenza A virus (CEF-Peptides) or left unstimulated. Furthermore, the concentration of spike-specific antibodies has been analyzed in patients.ResultsOur results indicate that hematologic malignancy patients developed a robust cellular immune response to SARS-CoV-2 vaccination comparable to that of healthy controls, and for certain T cell subtypes even higher. The most reactive T cells to SARS-CoV-2 spike peptides belonged to the CD4 and Tfh cell compartment, being median (IQR), 3.39 (1.41-5.92) and 2.12 (0.55-4.14) as a percentage of IFN- and TNF-producing Tfh cells in patients. In this regard, the immunomodulatory treatment of patients before the vaccination period seems important as it was strongly associated with a higher percentage of activated CD4 and Tfh cells. SARS-CoV-2- and CEF-specific T cell responses significantly correlated with each other. Compared to lymphoma patients, myeloma patients had an increased percentage of SARS-CoV-2-specific Tfh cells. T-SNE analysis revealed higher frequencies of γδT cells in patients compared to controls, especially in myeloma patients. In general, after vaccination, SARS-CoV-2-specific T cells were also detectable in patients without seroconversion.ConclusionHematologic malignancy patients are capable of developing a SARS-CoV-2-specific CD4 and Tfh cellular immune response after vaccination, and certain immunomodulatory therapies in the period before vaccination might increase the antigen-specific immune response. A proper response to recall antigens (e.g., CEF-Peptides) reflects immune cellular functionality and might be predictive for generating a newly induced antigen-specific immune response as is expected after SARS-CoV-2 vaccination.
PepSim: T-cell cross-reactivity prediction via comparison of peptide sequence and peptide-HLA structure
Authors: Hall-Swan Sarah , Slone Jared , Rigo Mauricio M. , Antunes Dinler A. , Lizée Gregory , Kavraki Lydia E. 
Published: April 2023

IntroductionPeptide-HLA class I (pHLA) complexes on the surface of tumor cells can be targeted by cytotoxic T-cells to eliminate tumors, and this is one of the bases for T-cell-based immunotherapies. However, there exist cases where therapeutic T-cells directed towards tumor pHLA complexes may also recognize pHLAs from healthy normal cells. The process where the same T-cell clone recognizes more than one pHLA is referred to as T-cell cross-reactivity and this process is driven mainly by features that make pHLAs similar to each other. T-cell cross-reactivity prediction is critical for designing T-cell-based cancer immunotherapies that are both effective and safe.MethodsHere we present PepSim, a novel score to predict T-cell cross-reactivity based on the structural and biochemical similarity of pHLAs.Results and discussionWe show our method can accurately separate cross-reactive from non-crossreactive pHLAs in a diverse set of datasets including cancer, viral, and self-peptides. PepSim can be generalized to work on any dataset of class I peptide-HLAs and is freely available as a web server at pepsim.kavrakilab.org.
Immune desert in MMR-deficient tumors predicts poor responsiveness of immune checkpoint inhibition
Authors: Zheng Guoxing , Lu Yingsi , Yang Zheng , Chen Hong , Liang Qian , Zhu Qingqing , Li Yan , Xiao Xing , He Zhuzhen , Zhu Yifan , Li Bo , Huang Leilei , Dong Nan , Hu Shuang , Pan Yihang , Zhang Changhua , Zhu Chengming 
Published: April 2023

BackgroundAlthough many efforts have been devoted to identify biomarkers to predict the responsiveness of immune checkpoint inhibitors, including expression of programmed death-ligand 1 (PD-L1) and major histocompatibility complex (MHC) I, microsatellite instability (MSI), mismatch repair (MMR) defect, tumor mutation burden (TMB), tertiary lymphoid structures (TLSs), and several transcriptional signatures, the sensitivity of these indicators remains to be further improved.Materials and methodsHere, we integrated T-cell spatial distribution and intratumor transcriptional signals in predicting the response to immune checkpoint therapy in MMR-deficient tumors including tumors of Lynch syndrome (LS).ResultsIn both cohorts, MMR-deficient tumors displayed personalized tumor immune signatures, including inflamed, immune excluded, and immune desert, which were not only individual-specific but also organ-specific. Furthermore, the immune desert tumor exhibited a more malignant phenotype characterized by low differentiation adenocarcinoma, larger tumor sizes, and higher metastasis rate. Moreover, the tumor immune signatures associated with distinct populations of infiltrating immune cells were comparable to TLSs and more sensitive than transcriptional signature gene expression profiles (GEPs) in immunotherapy prediction. Surprisingly, the tumor immune signatures might arise from the somatic mutations. Notably, patients with MMR deficiency had benefited from the typing of immune signatures and later immune checkpoint inhibition.ConclusionOur findings suggest that compared to PD-L1 expression, MMR, TMB, and GEPs, characterization of the tumor immune signatures in MMR-deficient tumors improves the efficiency of predicting the responsiveness of immune checkpoint inhibition.
Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection
Authors: Antar Annukka A. R. , Yu Tong , Demko Zoe O , Hu Chen , Tornheim Jeffrey A. , Blair Paul W. , Thomas David L. , Manabe Yukari C. 
Published: April 2023

IntroductionThe incidence of long COVID is substantial, even in people with mild to moderate acute COVID-19. The role of early viral kinetics in the subsequent development of long COVID is largely unknown, especially in individuals who were not hospitalized for acute COVID-19.MethodsSeventy-three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS-CoV-2 RT-PCR test, and mid-turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS-CoV-2 using RT-PCR and additional SARS-CoV-2 test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long COVID symptoms at 1-, 3-, 6-, 12-, and 18-months post-COVID-19 diagnosis. Time from acute COVID-19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90+ days from acute COVID-19 symptom onset.ResultsSelf-reported brain fog and muscle pain at 90+ days after acute COVID-19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID-19 onset with adjustment for age, sex, BMI ≥ 25, and COVID vaccination status prior to COVID-19 (brain fog: aRR 0.46, 95% CI 0.22-0.95; muscle pain: aRR 0.28, 95% CI 0.08-0.94). Participants reporting higher severity brain fog or muscle pain at 90+ days after acute COVID-19 onset were less likely to have cleared SARS-CoV-2 RNA within 28 days. The acute viral RNA decay trajectories of participants who did and did not later go on to experience brain fog 90+ days after acute COVID-19 onset were distinct.DiscussionThis work indicates that at least two long COVID symptoms - brain fog and muscle pain – at 90+ days from acute COVID-19 onset are specifically associated with prolonged time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute COVID-19. This finding provides evidence that delayed immune clearance of SARS-CoV-2 antigen or greater amount or duration of viral antigen burden in the upper respiratory tract during acute COVID-19 are directly linked to long COVID. This work suggests that host-pathogen interactions during the first few weeks after acute COVID-19 onset have an impact on long COVID risk months later.
Inactivated ostreid herpesvirus-1 induces an innate immune response in the Pacific oyster, Crassostrea gigas, hemocytes
Authors: Delisle Lizenn , Rolton Anne , Vignier Julien 
Published: April 2023

Infectious diseases are a major constraint to the expansion of shellfish production worldwide. Pacific oyster mortality syndrome (POMS), a polymicrobial disease triggered by the Ostreid herpesvirus-1 (OsHV-1), has devastated the global Pacific oyster (Crassostrea gigas) aquaculture industry. Recent ground-breaking research revealed that C. gigas possess an immune memory, capable of adaption, which improves the immune response upon a second exposure to a pathogen. This paradigm shift opens the door for developing ‘vaccines’ to improve shellfish survival during disease outbreaks. In the present study, we developed an in-vitro assay using hemocytes – the main effectors of the C. gigas immune system – collected from juvenile oysters susceptible to OsHV-1. The potency of multiple antigen preparations (e.g., chemically and physically inactivated OsHV-1, viral DNA, and protein extracts) to stimulate an immune response in hemocytes was evaluated using flow cytometry and droplet digital PCR to measure immune-related subcellular functions and gene expression, respectively. The immune response to the different antigens was benchmarked against that of hemocytes treated with Poly (I:C). We identified 10 antigen preparations capable of inducing immune stimulation in hemocytes (ROS production and positively expressed immune- related genes) after 1 h of exposure, without causing cytotoxicity. These findings are significant, as they evidence the potential for priming the innate immunity of oysters using viral antigens, which may enable cost-effective therapeutic treatment to mitigate OsHV-1/POMS. Further testing of these antigen preparations using an in-vivo infection model is essential to validate promising candidate pseudo-vaccines.
The inflammatory injury in the striatal microglia-dopaminergic-neuron crosstalk involved in Tourette syndrome development
Authors: Wang Xueming , Liu Xiumei , Chen Liangliang , Zhang Xiaoling 
Published: April 2023

BackgroundTourette syndrome (TS) is associated with immunological dysfunction. The DA system is closely related to TS development, or behavioral stereotypes. Previous evidence suggested that hyper-M1-polarized microglia may exist in the brains of TS individuals. However, the role of microglia in TS and their interaction with dopaminergic neurons is unclear. In this study, we applied iminodipropionitrile (IDPN) to establish a TS model and focused on the inflammatory injury in the striatal microglia-dopaminergic-neuron crosstalk.MethodsMale Sprague–Dawley rats were intraperitoneally injected with IDPN for seven consecutive days. Stereotypic behavior was observed to verify the TS model. Striatal microglia activation was evaluated based on different markers and expressions of inflammatory factors. The striatal dopaminergic neurons were purified and co-cultured with different microglia groups, and dopamine-associated markers were assessed.ResultsFirst, there was pathological damage to striatal dopaminergic neurons in TS rats, as indicated by decreased expression of TH, DAT, and PITX3. Next, the TS group showed a trend of increased Iba-1 positive cells and elevated levels of inflammatory factors TNF-α and IL-6, as well as an enhanced M1-polarization marker (iNOS) and an attenuated M2-polarization marker (Arg-1). Finally, in the co-culture experiment, IL-4-treated microglia could upregulate the expression of TH, DAT, and PITX3 in striatal dopaminergic neurons vs LPS-treated microglia. Similarly, the TS group (microglia from TS rats) caused a decreased expression of TH, DAT, and PITX3 compared with the Sham group (microglia from control rats) in the dopaminergic neurons.ConclusionIn the striatum of TS rats, microglia activation is M1 hyperpolarized, which transmits inflammatory injury to striatal dopaminergic neurons and disrupts normal dopamine signaling.
Clinical-pathological features and muscle imaging findings in 36 Chinese patients with rimmed vacuolar myopathies: case series study and review of literature
Authors: Wei Xiao-jing , Sun Hui , Miao Jing , Qiu Ru-qing , Jiang Zong-zhi , Ma Zhen-wei , Sun Wei , Yu Xue-fan 
Published: April 2023

IntroductionRimmed vacuolar myopathies (RVMs) are a group of genetically heterogeneous diseases that share histopathological characteristics on muscle biopsy, including the aberrant accumulation of autophagic vacuoles. However, the presence of non-coding sequences and structural mutations, some of which remain undetectable, confound the identification of pathogenic mutations responsible for RVMs. Therefore, we assessed the clinical profiles and muscle magnetic resonance imaging (MRI) changes in 36 Chinese patients with RVMs, emphasizing the role of muscle MRI in disease identification and differential diagnosis to propose a comprehensive literature-based imaging pattern to facilitate improved diagnostic workup.MethodsAll patients presented with rimmed vacuoles with varying degrees of muscular dystrophic changes and underwent a comprehensive evaluation using clinical, morphological, muscle MRI and molecular genetic analysis. We assessed muscle changes in the Chinese RVMs and provided an overview of the RVMs, focusing on the patterns of muscle involvement on MRI.ResultsA total of 36 patients, including 24 with confirmed distal myopathy and 12 with limb-girdle phenotype, had autophagic vacuoles with RVMs. Hierarchical clustering of patients according to the predominant effect of the distal or proximal lower limbs revealed that most patients with RVMs could be distinguished. GNE myopathy was the most prevalent form of RVMs observed in this study. Moreover, MRI helped identify the causative genes in some diseases (e.g., desminopathy and hereditary myopathy with early respiratory failure) and confirmed the pathogenicity of a novel mutation (e.g., adult-onset proximal rimmed vacuolar titinopathy) detected using next-generation sequencing.DiscussionCollectively, our findings expand our knowledge of the genetic spectrum of RVMs in China and suggest that muscle imaging should be an integral part of assisting genetic testing and avoiding misdiagnosis in the diagnostic workup of RVM.
MRI characteristics of lumbosacral dural arteriovenous fistulas
Authors: Zhu Jinyu , Zhu Wangshu , Li Minghua , Wei Xiaoer , Chen Zheyi , Li Yuehua 
Published: April 2023

Background and purposeSpinal dural arteriovenous fistulas located in the lumbosacral region are rare and present with nonspecific clinical signs. The purpose of this study was to find out the specific radiologic features of these fistulas.MethodsWe retrospectively reviewed the clinical and radiological data of 38 patients diagnosed with lumbosacral spinal dural arteriovenous fistulas in our institution from September 2016 to September 2021. All patients underwent time-resolved contrast-enhanced three-dimensional MRA and DSA examinations, and were treated with either endovascular or neurosurgical strategies.ResultsMost of the patients (89.5%) had motor or sensory disorders in both lower limbs as the first symptoms. On MRA, the dilated filum terminale vein or radicular vein was seen in 23/30 (76.7%) patients with lumbar spinal dural arteriovenous fistulas and 8/8 (100%) patients with sacral spinal dural arteriovenous fistulas. T2W intramedullary abnormally high signal intensity areas were found in all lumbosacral spinal dural arteriovenous fistula patients, with involvement of the conus present in 35/38 (92.1%) patients. The “missing piece sign” in the intramedullary enhancement area was seen in 29/38 (76.3%) patients.ConclusionDilatation of the filum terminale vein or radicular vein is powerful evidence for diagnosis of lumbosacral spinal dural arteriovenous fistulas, especially for sacral spinal dural arteriovenous fistulas. T2W intramedullary hyperintensity in the thoracic spinal cord and conus, and the missing-piece sign could be indicative of lumbosacral spinal dural arteriovenous fistula.
Is repetitive systemic corticosteroid therapy effective for idiopathic sudden sensorineural hearing loss? a retrospective study
Authors: Yamamoto Kengo , Kurioka Takaomi , Ohki Motofumi , Sano Hajime , Yamashita Taku 
Published: April 2023

IntroductionSome idiopathic sudden sensorineural hearing loss (ISSHL) cases experience repetitive systemic corticosteroid treatment, but studies focusing on repetitive systemic corticosteroid administration have not been reported. Thus, we investigated the clinical characteristics and usefulness of repetitive systemic corticosteroid treatment in ISSHL cases.MethodsWe reviewed the medical records of 103 patients who received corticosteroids only in our hospital (single-treatment group), and 46 patients who presented at our hospital after receiving corticosteroids in a nearby clinic and were subsequently treated with corticosteroids again in our hospital (repetitive-treatment group). Clinical backgrounds, hearing thresholds, and hearing prognosis were assessed.ResultsThe final hearing outcomes were not different between the two groups. Further, in the repetitive-treatment group, statistical differences were found between the good and poor prognosis groups in the number of days to start corticosteroid administration (p = 0.03), the dose of corticosteroid (p = 0.02), and the duration of corticosteroid administration (p = 0.02) at the previous facility. Multivariate analysis revealed a significant difference in the dose of corticosteroids administered by the previous clinic (p = 0.004).ConclusionThe repetitive systemic corticosteroid administration might play a supplementary role in hearing improvement, and initial sufficient corticosteroid administration would lead to good hearing outcomes in an early phase of ISSHL.
Effects of 12 weeks of Tai Chi on neuromuscular responses and postural control in elderly patients with sarcopenia: a randomized controlled trial
Authors: Huang Dunbing , Ke Xiaohua , Jiang Cai , Song Wei , Feng Jing , Zhou Huiting , Zhang Rui , Zhang Anren , Lan Fujun 
Published: April 2023

ObjectiveTo explore the effect of 12 weeks of Tai Chi on neuromuscular responses and postural control in elderly patients with sarcopenia.MethodsOne hundred and twenty-four elderly patients with sarcopenia from ZheJiang Hospital and surrounding communities were selected, however, 64 were later disqualified. Sixty elderly patients with sarcopenia were randomly assigned to the Tai Chi group (n = 30) and the control group (n = 30). Both groups received 45-min health education sessions once every 2 weeks for 12 weeks, and the Tai Chi group engaged in 40-min simplified eight-style Tai Chi exercise sessions 3 times per week for 12 weeks. Two assessors who had received professional training and were unaware of the intervention allocation assessed the subjects within 3 days prior to the intervention and within 3 days after completion of the intervention. They chose the unstable platform provided by the dynamic stability test module in ProKin 254 to evaluate the patient’s postural control ability. Meanwhile, surface EMG was utilized to assess the neuromuscular response during this period.ResultsAfter 12 weeks of intervention, the Tai Chi group showed a significant decrease in neuromuscular response times of the rectus femoris, semitendinosus, anterior tibialis, and gastrocnemius and overall stability index (OSI) compared to before the intervention (p &lt; 0.05), while there was no significant difference in the control group for these indicators before and after intervention (p &gt; 0.05). In addition, these indicators in the Tai Chi group were significantly lower than those in the control group (p &lt; 0.05). The changes in neuromuscular response times of the rectus femoris, semitendinosus, anterior tibialis, and gastrocnemius were positively correlated with the changes in OSI (p &lt; 0.05) in the Tai Chi group, but there were no significant correlations between changes in neuromuscular response times of the aforementioned muscles and changes in OSI in the control group (p &lt; 0.05).ConclusionTwelve-weeks of Tai Chi exercise can improve the neuromuscular response of the lower extremities in elderly patients with sarcopenia, shorten their neuromuscular response time when balance is endangered, enhance their dynamic posture control ability, and ultimately reduce the risk of falls.