bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid cell MHC I expression drives CD8+ T cell activation in nonalcoholic steatohepatitis
Authors: Adams Victoria R. , Collins Leonard B. , Williams Taufika Islam , Holmes Jennifer , Hess Paul , Atkins Hannah M. , Scheidemantle Grace , Liu Xiaojing , Lodge Mareca , Johnson Aaron J. , Kennedy Arion 
Published: January 2024

Background &amp; aimsActivated CD8+ T cells are elevated in Nonalcoholic steatohepatitis (NASH) and are important for driving fibrosis and inflammation. Despite this, mechanisms of CD8+ T cell activation in NASH are largely limited. Specific CD8+ T cell subsets may become activated through metabolic signals or cytokines. However, studies in NASH have not evaluated the impact of antigen presentation or the involvement of specific antigens. Therefore, we determined if activated CD8+ T cells are dependent on MHC class I expression in NASH to regulate fibrosis and inflammation.MethodsWe used H2Kb and H2Db deficient (MHC I KO), Kb transgenic mice, and myeloid cell Kb deficient mice (LysM Kb KO) to investigate how MHC class I impacts CD8+ T cell function and NASH. Flow cytometry, gene expression, and histology were used to examine hepatic inflammation and fibrosis. The hepatic class I immunopeptidome was evaluated by mass spectrometry.ResultsIn NASH, MHC class I isoform H2Kb was upregulated in myeloid cells. MHC I KO demonstrated protective effects against NASH-induced inflammation and fibrosis. Kb mice exhibited increased fibrosis in the absence of H2Db while LysM Kb KO mice showed protection against fibrosis but not inflammation. H2Kb restricted peptides identified a unique NASH peptide Ncf2 capable of CD8+ T cell activation in vitro. The Ncf2 peptide was not detected during fibrosis resolution.ConclusionThese results suggest that activated hepatic CD8+ T cells are dependent on myeloid cell MHC class I expression in diet induced NASH to promote inflammation and fibrosis. Additionally, our studies suggest a role of NADPH oxidase in the production of Ncf2 peptide generation.
Immunogenicity and reactogenicity of repeated intradermal mRNA COVID-19 vaccines administered as a second booster dose in a Thai geriatric population
Authors: Assantachai Prasert , Niyomnaitham Suvimol , Toh Zheng Quan , Thammasalee Monthira , Pengsorn Napaporn , Monklang Wiyachatr , Licciardi Paul V. , Chokephaibulkit Kulkanya 
Published: January 2024

BackgroundGeriatric populations are at an increased risk of severe presentations, hospitalization, and loss of life from COVID-19. Few studies have explored vaccination regimens in adults &gt;65 years old. Repeated booster vaccination is required for high-risk populations as COVID-19 vaccine efficacy is short-lived. We compared the immunogenicity and reactogenicity of second intradermal (ID) COVID-19 booster vaccination with second intramuscular (IM) vaccination in older adults.MethodsThis single-center, open-labeled, prospective, cohort study conducted at Siriraj Hospital enrolled older adults ≥65 years old who previously received a first booster (third dose) mRNA vaccine (mRNA-1273 or BNT162b2) via ID or IM administration. Participants were allocated to receive a second booster of the same vaccine type and route as their first booster 16–17 weeks thereafter. Anti-SARS-CoV-2 receptor binding domain IgG and neutralizing antibody titers against Wuhan and Omicron subvariants (BA.1, BA.2, and BA.4/5) were measured 2 weeks after vaccination.ResultsOf 91 enrolled participants, 72.5% were women, with a median age of 75 years. Forty-nine participants (53.8%) received a second ID booster, and 42 (46.2%) received a second IM booster. Two weeks after the second booster, all groups generated anamnestic IgG antibody responses that were 5.41- to 10.00-fold higher than at baseline. Overall, higher antibody GMTs against Wuhan and Omicron subvariants were observed in IM compared with ID regimens. ID mRNA-1273 induced similar GMTs to IM BNT162b2 2 weeks after the second booster against Wuhan (486.77 [321.48, 737.05] vs. 472.63 [291.24, 767.01], respectively; p = 0.072). Higher GMTs against Omicron BA.1 (GMR [95% CI], 1.71 [1.39, 2.11]; p = 0.023), BA.2 (1.34 [1.11, 1.62]; p = 0.845), and BA.4/5 (1.10 [0.92, 1.33]; p = 0.531) were seen in all groups at 2 weeks after the second booster compared with 2–4 weeks after the first booster. Both local and systemic AEs were less frequent after the second than after the first booster, regardless of administrative route and vaccine type. Local AEs were significantly more frequent in ID mRNA-1273 arms than their respective BNT162b2 arms 2 weeks after the second booster (ID-mRNA-1273 vs. ID-BNT162b2: p ≤ 0.001).ConclusionRepeated fractional ID vaccination may be an alternative booster vaccination strategy for geriatric populations.
Rational use of eculizumab in secondary atypical hemolytic uremic syndrome
Authors: Cordero Lucía , Cavero Teresa , Gutiérrez Eduardo , Trujillo Hernando , Sandino Justo , Auñón Pilar , Rivero Marta , Morales Enrique 
Published: January 2024

BackgroundSecondary atypical hemolytic uremic syndrome (secondary aHUS) is a heterogeneous group of thrombotic microangiopathies (TMA) associated with various underlying conditions. Unlike primary aHUS, there is still no hard evidence on the efficacy of complement blockade in secondary aHUS, since the two main series that investigated this subject showed discrepant results. Our work aims to reassess the efficacy of eculizumab in treating secondary aHUS.MethodsObservational, retrospective, single-center study, in which we analyzed the hematological and renal evolution of 23 patients diagnosed with secondary aHUS who received treatment with eculizumab and compared them with a control cohort of 14 patients. Complete renal response was defined as the recovery of renal function before the event, partial renal response as a recovery of 50% of lost glomerular filtration rate, and hematological response as normalization of hemoglobin and platelets.ResultsWe found no statistically significant differences in baseline characteristics or disease severity between both groups. After a median of 5 doses of eculizumab, the group of patients who received complement blockade presented a significant difference in renal response (complete in 52.3% of patients and partial in 23.8%) compared to the control cohort (complete response 14.3% and partial of 14.3%). Rates of hematological remission were similar in both groups (90.9% in the eculizumab cohort and 85.7% in the control cohort).ConclusionEarly and short-term use of eculizumab in patients with secondary aHUS could be an effective and safe therapeutic option, assuring better renal recovery compared to patients who do not receive complement blockade.
Single cell sequencing revealed the mechanism of CRYAB in glioma and its diagnostic and prognostic value
Authors: Cai Hua-Bao , Zhao Meng-Yu , Li Xin-Han , Li Yu-Qing , Yu Tian-Hang , Wang Cun-Zhi , Wang Li-Na , Xu Wan-Yan , Liang Bo , Cai Yong-Ping , Zhang Fang , Hong Wen-Ming 
Published: January 2024

BackgroundWe explored the characteristics of single-cell differentiation data in glioblastoma and established prognostic markers based on CRYAB to predict the prognosis of glioblastoma patients. Aberrant expression of CRYAB is associated with invasive behavior in various tumors, including glioblastoma. However, the specific role and mechanisms of CRYAB in glioblastoma are still unclear.MethodsWe assessed RNA-seq and microarray data from TCGA and GEO databases, combined with scRNA-seq data on glioma patients from GEO. Utilizing the Seurat R package, we identified distinct survival-related gene clusters in the scRNA-seq data. Prognostic pivotal genes were discovered through single-factor Cox analysis, and a prognostic model was established using LASSO and stepwise regression algorithms. Moreover, we investigated the predictive potential of these genes in the immune microenvironment and their applicability in immunotherapy. Finally, in vitro experiments confirmed the functional significance of the high-risk gene CRYAB.ResultsBy analyzing the ScRNA-seq data, we identified 28 cell clusters representing seven cell types. After dimensionality reduction and clustering analysis, we obtained four subpopulations within the oligodendrocyte lineage based on their differentiation trajectory. Using CRYAB as a marker gene for the terminal-stage subpopulation, we found that its expression was associated with poor prognosis. In vitro experiments demonstrated that knocking out CRYAB in U87 and LN229 cells reduced cell viability, proliferation, and invasiveness.ConclusionThe risk model based on CRYAB holds promise in accurately predicting glioblastoma. A comprehensive study of the specific mechanisms of CRYAB in glioblastoma would contribute to understanding its response to immunotherapy. Targeting the CRYAB gene may be beneficial for glioblastoma patients.
An innovative gene expression modulating strategy by converting nucleic acids into HNC therapeutics using carrier-free nanoparticles
Authors: Liu Heyuan , Huang Yinong , Li Zongfang , Han Suxia , Liu Tianya , Zhao Qian 
Published: January 2024

BackgroundCell fate and microenvironmental changes resulting from aberrant expression of specific proteins in tumors are one of the major causes of inadequate anti-tumor immune response and poor prognosis in head and neck cancer (HNC). Eukaryotic initiation factor 3C (eIF3c) has emerged as a promising therapeutic target for HNC due to its ability to regulate protein expression levels in tumor cells, but its drug development is difficult to achieve by targeting traditional protein-protein interactions. siRNA has emerged as a highly promising modality for drug development targeting eIF3c, while its application is hindered by challenges pertaining to inadequate stability and insufficient concentration specifically within tumor sites.MethodWe employed a method to convert flexible siRNAs into stable and biologically active infinite Auric-sulfhydryl coordination supramolecular siRNAs (IacsRNAs). Through coordinated self-assembly, we successfully transformed eIF3C siRNAs into the carrier-free HNC nanotherapeutic agent Iacs-eif3c-RNA. The efficacy of this agent was evaluated in vivo using HNC xenograft models, demonstrating promising antitumor effects.ResultsIacs-eif3c-RNA demonstrated the ability to overcome the pharmacological obstacle associated with targeting eIF3C, resulting in a significant reduction in eIF3C expression within tumor tissues, as well as effective tumor cell proliferating suppression and apoptosis promotion. In comparison to monotherapy utilizing the chemotherapeutic agent cisplatin, Iacs-eif3c-RNA exhibited superior anti-tumor efficacy and favorable biosafety.ConclusionThe utilization of Iacs-eif3c-RNA as a carrier-free nanotherapeutic agent presents a promising and innovative approach for addressing HNC treating challenges. Moreover, this strategy demonstrates potential for the translation of therapeutic siRNAs into clinical drugs, extending its applicability to the treatment of other cancers and various diseases.
Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient’s global assessment of disease activity in rheumatoid arthritis
Authors: Arntz Onno J. , Thurlings Rogier M. , Blaney Davidson Esmeralda N. , Jansen Pascal W. T. C. , Vermeulen Michiel , Koenders Marije I. , van der Kraan Peter M. , van de Loo Fons A. J. 
Published: January 2024

BackgroundRheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial inflammation and cartilage/bone damage. Intercellular messengers such as IL-1 and TNF play a crucial role in the pathophysiology of RA but have limited diagnostic and prognostic values. Therefore, we assessed whether the protein content of the recently discovered extracellular vesicles (EVs), which have gained attention in the pathogenesis of RA, correlates with disease activity parameters in RA patients.MethodsWe identified and quantified proteins in plasma-derived EVs (pEVs), isolated by size exclusion chromatography from 17 RA patients by mass spectrophotometry (MS). Quantified protein levels were correlated with laboratory and clinical parameters and the patient’s own global assessment of their disease activity (PGA-VAS). In a second MS run, the pEV proteins of nine other RA patients were quantified and compared to those from nine healthy controls (HC).ResultsNo differences were observed in the concentration, size, and protein content of pEVs from RA patients. Proteomics revealed &gt;95% overlapping proteins in RA-pEVs, compared to HC-pEVs (data are available via ProteomeXchange with identifier PXD046058). Remarkably, in both runs, the level of far more RA-pEV proteins correlated positively to PGA-VAS than to either clinical or laboratory parameters. Interestingly, all observed PGA-VAS positively correlated RA-pEV proteins were associated with the actin-cytoskeleton linker proteins, ezrin, and moesin.ConclusionOur observation suggests that PGA-VAS (loss of vitality) may have a different underlying pathological mechanism in RA, possibly related to enhanced muscle actin-cytoskeleton activity. Furthermore, our study contributes to the growing awareness and evidence that pEVs contain valuable biomarkers for diseases, with added value for RA patients.
Resurgence of influenza A after SARS-CoV-2 omicron wave and comparative analysis of hospitalized children with COVID-19 and influenza A virus infection
Authors: Lin Fen , Chen Man-Tong , Zhang Lin , Wu Min , Xie He , Guan Ze-Xiang , Yang Zhe , Cai Zhong-Xian , Wen Jin-Zhou , Yang Li-Ye 
Published: January 2024

ContextThe highly infectious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused large-scale transmission from Dec 2022 to Feb 2023 in China. After this event, a remarkable surge of influenza A (Flu A) occurred from March to May 2023, especially in pediatric patients.ObjectivesThis study aimed to investigate the differences between pediatric patients infected with COVID-19 Omicron and Flu A virus.MethodsA total of 1,063 hospitalized children who admitted into two tertiary general hospital of Guangdong province of China were included. Medical records were compared retrospectively in these patients during the pandemic periods of SARS-CoV-2 omicron and Flu A.ResultsA total of 592 Patients with Flu A were mostly preschool and school-aged (&gt;3y, 76.0%), they showed higher ratio of high fever (≥39°C), cough, rhinorrhea, and vomiting than patients with SARS-CoV-2 omicron. Most of the 471 Omicron patients were young children (0–3y, 74.5%) and had more poor appetite and dyspnea symptom. Benign acute children myositis (BACM) was only observed in patients with Flu A, and a significant male predominance. Multisystem inflammatory syndrome in children (MIS-C) was only found in patients with SARS-CoV-2 Omicron. Compared to the SARS-CoV-2 Omicron group, for both age groups (0–3 years and &gt; 3 years), the Flu A group showed significantly reduced lymphocyte (Lym) counts (P &lt; 0.001), and elevated levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatinine kinase-MB (CK-MB) in laboratory indexes (all P &lt; 0.001). Additionally, it was found that more children hospitalized with COVID-19 had increased C-reactive protein (CRP) levels compared to those with Flu A.ConclusionInfluenza A infections have notably surged in children, coinciding with the relaxation of COVID-19 related social restrictions. During the epidemic periods of Omicron and Flu A virus infection, different clinical and laboratory characteristics were observed in hospitalized children.
Fecal and oral microbiome analysis of snakes from China reveals a novel natural emerging disease reservoir
Authors: Hu Xiaoliang , Yang Lu , Zhang Yue , Yang Manman , Li Jiayi , Fan Yuping , Guo Peng , Tian Zhige 
Published: January 2024

IntroductionThe gastrointestinal tract and oral cavity of animal species harbor complex microbial communities, the composition of which is indicative of the behavior, co-evolution, diet, and immune system of the host.MethodsThis study investigated the microbial composition in snakes from varying altitudinal ranges by assessing the fecal and oral bacterial communities in Protobothrops mucrosquamatus, Elaphe dione, and Gloydius angusticeps from Sichuan Province, China, using metagenomic sequencing.Results and discussionIt was revealed that Bacteroidetes, Proteobacteria, Firmicutes, and Fusobacteria were the core microbial phyla in fecal samples across all three species, while Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes were the core microbial phyla in oral samples across all three species. Notably, the dominance of Armatimonadetes was documented for the first time in the feces of all three species. Comparative analysis of the microbiomes of the three species indicated distinct microbiological profiles between snakes living at low- and high-altitude regions. Furthermore, 12 to 17 and 22 to 31 bacterial pathogens were detected in the oral and fecal samples, respectively, suggesting that snakes may serve as a novel reservoir for emerging diseases. Overall, this study provides a comparative analysis of the fecal and oral microbiomes in three snake species. Future investigations are anticipated to further elucidate the influence of age, genetics, behavior, diet, environment, ecology, and evolution on the gut and oral microbial communities of snakes.
Bi-sinusoidal light stimulation reveals an enhanced response power and reduced phase coherence at the visual cortex in migraine
Authors: van den Hoek Thomas C. , Perenboom Matthijs J. L. , Terwindt Gisela M. , Tolner Else A. , van de Ruit Mark 
Published: January 2024

IntroductionMigraine is associated with enhanced visual sensitivity during and outside attacks. Processing of visual information is a highly non-linear process involving complex interactions across (sub)cortical networks. In this exploratory study, we combined electroencephalography with bi-sinusoidal light stimulation to assess non-linear features of visual processing in participants with migraine.MethodsTwenty participants with migraine (10 with aura, 10 without aura) and ten non-headache controls were measured (outside attacks). Participants received bi-sinusoidal 13 + 23 Hz red light visual stimulation. Electroencephalography spectral power and multi-spectral phase coherence were compared between groups at the driving stimulation frequencies together with multiples and combinations of these frequencies (harmonic and intermodulation frequencies) caused by non-linearities.ResultsOnly at the driving frequency of 13 Hz higher spectral power was found in migraine with aura participants compared with those with migraine without aura and controls. Differences in phase coherence were present for 2nd, 4th, and 5th-order non-linearities in those with migraine (migraine with and without aura) compared with controls. Bi-sinusoidal light stimulation revealed evident non-linearities in the brain’s electroencephalography response up to the 5th order with reduced phase coherence for higher order interactions in interictal participants with migraine.DiscussionInsight into interictal non-linear visual processing may help understand brain dynamics underlying migraine attack susceptibility. Future research is needed to determine the clinical value of the results.
Mental states in caregivers toward people with Alzheimer’s disease at different stages
Authors: Li Bei , Jin Haiqiang , Yan Guiying , Zhang Chen , Chen Siwei , Wang Yue , Wang Ting , Wan Qiaoqin , Wei Zhimin , Sun Yongan 
Published: January 2024

IntroductionCaring for people with Alzheimer’s disease (AD) is burdensome, especially when family members act as caregivers. This multicenter survey first aimed to investigate caregivers’ mental states as well as its influencing factors in caring for people with different severities of AD in China.MethodsPeople with AD and their caregivers from 30 provincial regions in mainland China were enrolled from October 2020 to December 2020 to be surveyed for caregivers’ mental states and living conditions, as well as caregivers’ attitudes toward treatment and caring. Logistic regression was used to explore the factors that influence the positive and negative states of caregivers who care for people with different stages of AD.ResultsA total of 1,966 valid questionnaires were analyzed (mild AD: 795, moderate AD: 521, severe AD: 650). A total of 73.6% of caregivers maintained normal states (mild group: 71.9%, moderate group: 73.9%, severe group: 75.2%; X2 = 2.023, p = 0.364), and the proportions of caregivers with positive and negative states were 26.3% (mild group: 38.4%, moderate group: 24.6%, severe group: 13.1%; X2 = 119.000, p &lt; 0.001) and 36.5% (mild group: 25.2%, moderate group: 36.9%, severe group: 50.2%; X2 = 96.417, p &lt; 0.001), respectively. The major factors that both influenced caregivers’ positive and negative states were the severity of AD, perceived efficacy of treatment, safety issues after AD dementia diagnosis and perceived social support (p &lt; 0.005), while neuropsychiatric symptoms causing stress in caregivers (p &lt; 0.001) only affected the negative states of caregivers. The results of further analysis according to disease severity showed that safety issues after AD dementia diagnosis (p &lt; 0.005) only made significant differences in the mild-to-moderate group.ConclusionTo reduce negative states and promote positive states among caregivers, flexible and sensitive caregiving support could be built on caregivers’ demands in caring for people with different stages of AD. The support of emotion, social functioning and nursing skills is one of the significant ways for health workers to enhance caregivers’ competency.
Gunshot-related nerve injuries of the upper extremities: clinical, electromyographic, and ultrasound features in 22 patients
Authors: Shields Lisa B. E. , Iyer Vasudeva G. , Zhang Yi Ping , Shields Christopher B. 
Published: January 2024

ObjectivesGunshot wounds of the upper extremities may cause permanent neurovascular injuries, leading to significant morbidity, chronic pain, functional loss, and disability. While there are many reports on the incidence and intraoperative findings in gunshot-related nerve injuries (GSNI) sustained during wars, there is a paucity of details pertaining to GSNI of the upper extremities in civilians. The goal of this paper is to provide the clinical, electrodiagnostic (EDX), and ultrasound (US) findings in 22 patients with GSNI of the upper extremities.MethodsThis is a retrospective study of patients referred for EDX studies to evaluate the presence of nerve injury after sustaining GSWs to the upper extremities. All patients underwent EDX studies, and 16 patients had US evaluations. Numerous metrics were documented including presenting symptoms, neurological abnormalities, EDX findings, and US features.ResultsThe forearm was the most frequent location of injury (8 [36%] patients). The ulnar nerve was the most common injured nerve (10 [45%] patients), followed by the brachial plexus (7 [32%] patients). All patients complained of muscle weakness; the most frequently affected muscles were the first dorsal interosseous (FDI) (14 [64%] patients) and abductor pollicis brevis (APB) (11 [50%] patients). Muscle atrophy was noted in 19 (86%) patients, 15 of whom had atrophy of the FDI. Axonotmesis was the type of nerve injury in all patients based on EDX studies. Of the 16 patients who underwent US studies, a neuroma in continuity was noted in 4 (25%) patients and neurotmesis in 1 (6.2%) patient. Eleven (69%) patients had enlarged and/or hypoechoic nerves.ConclusionsAxonotmesis of the ulnar nerve was the most common finding among patients sustaining gunshot injuries to the upper extremities. EDX and US studies provide valuable insight into the underlying pathophysiology and guidance for management of patients with GSNI of the upper extremities.