bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chrysanthemum sporopollenin: A novel vaccine delivery system for nasal mucosal immunity
Authors: Liu Jun , Yan Xiao-Dan , Li Xian-Qiang , Du Yu-Hao , Zhu Li-Li , Ye Tian-Tian , Cao Ze-Ying , Dong Zhe-Wen , Li Shu-Tao , Xu Xue , Bai Wei , Li Dan , Zhang Ji-Wen , Wang Shu-Jun , Li Shan-Hu , Sun Jin , Yin Xian-Zhen 
Published: February 2023

ObjectiveMucosal immunization was an effective defender against pathogens. Nasal vaccines could activate both systemic and mucosal immunity to trigger protective immune responses. However, due to the weak immunogenicity of nasal vaccines and the lack of appropriate antigen carriers, very few nasal vaccines have been clinically approved for human use, which was a major barrier to the development of nasal vaccines. Plant-derived adjuvants are promising candidates for vaccine delivery systems due to their relatively safe immunogenic properties. In particular, the distinctive structure of pollen was beneficial to the stability and retention of antigen in the nasal mucosa.MethodsHerein, a novel wild-type chrysanthemum sporopollenin vaccine delivery system loaded with a w/o/w emulsion containing squalane and protein antigen was fabricated. The unique internal cavities and the rigid external walls within the sporopollenin skeleton construction could preserve and stabilize the inner proteins. The external morphological characteristics were suitable for nasal mucosal administration with high adhesion and retention.ResultsSecretory IgA antibodies in the nasal mucosa can be induced by the w/o/w emulsion with the chrysanthemum sporopollenin vaccine delivery system. Moreover, the nasal adjuvants produce a stronger humoral response (IgA and IgG) compared to squalene emulsion adjuvant. Mucosal adjuvant benefited primarily from prolongation of antigens in the nasal cavity, improvement of antigen penetration in the submucosa and promotion of CD8+ T cells in spleen.DisccusionBased on effective delivering both the adjuvant and the antigen, the increase of protein antigen stability and the realization of mucosal retention, the chrysanthemum sporopollenin vaccine delivery system has the potential to be a promising adjuvant platform. This work provide a novel idea for the fabrication of protein-mucosal delivery vaccine.
Comparing serum ferritin levels during COVID-19 infection and recovery period in pediatric patients with transfusion-dependent thalassemia, a single-center study
Authors: Marhaeni Wulandewi , Felicia Fabiola Vania , Sumadi Jap Arvin Leonard , Hartoyo Edi , Andayani Pudji 
Published: February 2023

BackgroundFerritin has been recognized as a predictor of severity among Coronavirus-19 disease (COVID-19) patients. Studies have shown higher levels of ferritin in patients with COVID-19 than in healthy children. Patients with transfusion-dependent thalassemia (TDT) basically have high ferritin level due to iron overload. It is uncertain whether serum ferritin level in these patients is associated with COVID-19 infection.ObjectiveTo evaluate ferritin levels in TDT with COVID-19 before, during, and after the course of infection.MethodsThis retrospective study enrolled all TDT children with COVID-19 infection that were hospitalized in Ulin General Hospital Banjarmasin during the COVID-19 pandemic (March 2020 to June 2022). Data were collected from medical records.ResultsThere were 14 patients included in this study, 5 patients had mild symptoms and 9 patients were asymptomatic. The mean of hemoglobin level upon admission was 8.1 ± 3 g/dL and serum ferritin level were 5148.5 ± 2651.8 ng/mL. The average serum ferritin level during COVID-19 infection was 2373.2 ng/mL higher than before infection and then decreased by 952.4 ng/mL after infection. We found no association of increasing serum ferritin with patients’ symptoms (p= 0.27). The severity of anemia also was not correlated with the presentation of COVID-19 infection (p= 0.902).ConclusionSerum ferritin levels in TDT children may not reflect disease severity or predict poor outcomes during COVID-19 infection. However, the presence of other co-morbid conditions/confounders warrants cautious interpretation.
Contaminants from a former Croatian coal sludge dictate the structure of microbiota in the estuarine (Raša Bay) sediment and soil
Authors: Zhang Weiting , Mo Qianyun , Huang Zaixing , Sabar Muhammad Adnan , Medunić Gordana , Ivošević Tatjana , He Huan , Urynowicz Michael , Liu Fang-Jing , Guo Hongguang , Haider Rizwan , Ali Muhammad Ishtiaq , Jamal Asif 
Published: February 2023

IntroductionCroatian superhigh-organic-sulfur Raša coal had been mined for nearly 400 years. The release of hazardous trace elements (HTEs) and toxic organic pollutants (TOPs) into the local environment by coal mining, preparation, and combustion activities has resulted in pollution.MethodsIn this study, the diversity and composition of microbial communities in estuarine sediment and soil samples as well as community function responses to the pollutants were investigated.ResultsThe results showed that PAH degradation does occur following 60 years of natural attenuation, the location is still heavily polluted by polycyclic aromatic hydrocarbons (PAHs) and HTEs. Microbial analyses have shown that high concentrations of PAHs have reduced the diversity and abundance of microbial communities. The pollution exerted an adverse, long-term impact on the microbial community structure and function in the brackish aquatic ecosystem. Microorganisms associated with the degradation of PAHs and sulfur-containing compounds have been enriched although the diversity and abundance of the microbial community have reduced. Fungi which are believed to be the main PAH degrader may play an important role initially, but the activity remains lower thereafter. It is the high concentrations of coal-derived PAHs, rather than HTEs, that have reduced the diversity and abundance of microbial communities and shaped the structure of the local microbiota.DiscussionThis study could provide a basis for the monitoring and restoration of ecosystems impacted by coal mining activities considering the expected decommission of a large number of coal plants on a global scale in the coming years due to growing global climate change concerns.
Detection of Klebsiella pneumonia DNA and ESBL positive strains by PCR-based CRISPR-LbCas12a system
Authors: Wang Shang , Wang Shan , Tang Ying , Peng Guoyu , Hao Tongyu , Wu Xincheng , Wei Jiehong , Qiu Xinying , Zhou Dewang , Zhu Shimao , Li Yuqing , Wu Song 
Published: February 2023

IntroductionKlebsiella pneumonia (K. pneumonia) is a Gram-negative bacterium that opportunistically causes nosocomial infections in the lung, bloodstream, and urinary tract. Extended-spectrum β-Lactamases (ESBLs)-expressed K. pneumonia strains are widely reported to cause antibiotic resistance and therapy failure. Therefore, early identification of K. pneumonia, especially ESBL-positive strains, is essential in preventing severe infections. However, clinical detection of K. pneumonia requires a time-consuming process in agar disk diffusion. Nucleic acid detection, like qPCR, is precise but requires expensive equipment. Recent research reveals that collateral cleavage activity of CRISPR-LbCas12a has been applied in nucleic acid detection, and the unique testing model can accommodate various testing models.MethodsThis study established a system that combined PCR with CRISPR-LbCas12a targeting the K. pneumoniae system. Additionally, this study summarized the antibiotic-resistant information of the past five years’ K. pneumoniae clinic cases in Luohu Hospital and found that the ESBL-positive strains were growing. This study then designs a crRNA that targets SHV to detect ESBL-resistant K. pneumoniae. This work is to detect K. pneumoniae and ESBL-positive strains’ nucleic acid using CRISPR-Cas12 technology. We compared PCR-LbCas12 workflow with PCR and qPCR techniques.Results and DiscussionThis system showed excellent detection specificity and sensitivity in both bench work and clinical samples. Due to its advantages, its application can meet different detection requirements in health centers where qPCR is not accessible. The antibiotic-resistant information is valuable for further research.
Age of first exposure to soccer heading: Associations with cognitive, clinical, and imaging outcomes in the Einstein Soccer Study
Authors: Charney Molly F. , Ye Kenny Q. , Fleysher Roman , DeMessie Bluyé , Stewart Walter F. , Zimmerman Molly E. , Kim Mimi , Lipton Richard B. , Lipton Michael L. 
Published: February 2023

IntroductionThe objective of this study is to assess the role of age at first exposure (AFE) to soccer heading as a predictor of known adverse associations of recent and longer-term heading with brain microstructure, cognitive, and behavioral features among adult amateur soccer players.MethodsThe sample included 276 active amateur soccer players (196 male and 81 female) aged 18–53 years old. AFE to soccer heading was treated as a binary variable, dichotomized at ≤ 10 years vs. &gt;10 years old, based on a recently promulgated US Soccer policy, which bans heading for athletes ages 10 and under.ResultsWe found that soccer players who began heading at age 10 or younger performed better on tests of working memory (p = 0.03) and verbal learning (p = 0.02), while accounting for duration of heading exposure, education, sex, and verbal intelligence. No difference in brain microstructure or behavioral measures was observed between the two exposure groups.DiscussionThe findings indicate that, among adult amateur soccer players, AFE to heading before age 10 compared to later start of heading, is not associated with adverse outcomes, and may be associated with better cognitive performance in young adulthood. Cumulative heading exposure across the lifespan, rather than early life exposure, may drive risk for adverse effects and should be the focus of future longitudinal studies to inform approaches to enhance player safety.
Ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease: A systematic review and critical appraisal
Authors: Bohnen Jeffrey L. B. , Albin Roger L. , Bohnen Nicolaas I. 
Published: February 2023

BackgroundThere is increasing interest in therapeutic ketosis as a potential therapy for neurodegenerative disorders–in particular, mild cognitive impairment (MCI), Alzheimer's disease (AD), and Parkinson's disease (PD)–following a proof-of-concept study in Parkinson's disease published in 2005.MethodsTo provide an objective assessment of emerging clinical evidence and targeted recommendations for future research, we reviewed clinical trials involving ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease reported since 2005. Levels of clinical evidence were systematically reviewed using the American Academy of Neurology criteria for rating therapeutic trials.Results10 AD, 3 MCI, and 5 PD therapeutic ketogenic trials were identified. Respective grades of clinical evidence were objectively assessed using the American Academy of Neurology criteria for rating therapeutic trials. We found class “B” evidence (probably effective) for cognitive improvement in subjects with mild cognitive impairment and subjects with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele (APOε4-). We found class “U” evidence (unproven) for cognitive stabilization in individuals with mild-to-moderate Alzheimer's disease positive for the apolipoprotein ε4 allele (APOε4+). We found class “C” evidence (possibly effective) for improvement of non-motor features and class “U” evidence (unproven) for motor features in individuals with Parkinson's disease. The number of trials in Parkinson's disease is very small with best evidence that acute supplementation holds promise for improving exercise endurance.ConclusionsLimitations of the literature to date include the range of ketogenic interventions currently assessed in the literature (i.e., primarily diet or medium-chain triglyceride interventions), with fewer studies using more potent formulations (e.g., exogenous ketone esters). Collectively, the strongest evidence to date exists for cognitive improvement in individuals with mild cognitive impairment and in individuals with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele. Larger-scale, pivotal trials are justified in these populations. Further research is required to optimize the utilization of ketogenic interventions in differing clinical contexts and to better characterize the response to therapeutic ketosis in patients who are positive for the apolipoprotein ε4 allele, as modified interventions may be necessary.
Association between dietary calcium and depression among American adults: National health and nutrition examination survey
Authors: Shen Xia , Gu Xue , Liu Yuan-Yuan , Yang Long , Zheng Meng , Jiang Lei 
Published: February 2023

BackgroundThere is only limited evidence for an association between calcium (Ca) and depression, and the relationship was inconsistent. Therefore, the aim of this study was to assess the relationship between dietary Ca and the risk of depressive symptoms in individuals over the age of 18 in the US.MethodsWe extracted 14,971 participants from the US National Health and Nutrition Examination Survey (NHANES) 2007–2016 to probe their associations. Dietary Ca intake was measured through 24 h dietary recall method. Patients with the Patient Health Questionnaire-9 (PHQ-9) ≥ 10 scores were believed to have depressive symptoms. The association between dietary Ca and depressive symptoms was investigated using multivariate logistic regression, sensitivity analysis, and restricted cubic spline regression.ResultsIn this study, 7.6% (1,144/14,971) of them had depressive symptoms. After adjusting for sex, age, race, poverty to income ratio (PIR), marital status, education, body mass index (BMI), caffeine intake, carbohydrates intake, total energy intake, smoking status, alcohol consumption, physical activity, diabetes, hypertension, severe cardiovascular disease (CVD), cancer, serum vitamin D, serum Ca, and Ca supplement, the adjusted ORs value [95% confidence interval (CI)] of depression for the lowest category (Q1 ≤ 534 mg/day) vs. Q2–Q4 of Ca intake were 0.83 (0.69–0.99), 0.97 (0.65–0.95), and 0.80 (0.63–0.98) with the p for trend (p = 0.014). The relationship between dietary Ca intake and depressive symptoms was linear (non-linear p = 0.148). None of the interactions were significant except among races (p for interaction = 0.001).ConclusionAssociation between dietary Ca and the prevalence of depressive symptoms in US adults. And Ca intake was negatively associated with the risk of depressive symptoms. As Ca intake increased, the prevalence of depressive symptoms decreased.
Acanthopanax trifoliatus (L.) Merr polysaccharides ameliorates hyperglycemia by regulating hepatic glycogen metabolism in type 2 diabetic mice
Authors: Lin Yuzi , Pan Jinghua , Liu Yue , Yang Huiwen , Wu Guoyu , Pan Yufang 
Published: February 2023

IntroductionDrug monotherapy was inadequate in controlling blood glucose levels and other comorbidities. An agent that selectively tunes multiple targets was regarded as a new therapeutic strategy for type 2 diabetes. Acanthopanax trifoliatus (L.) Merr polysaccharide (ATMP) is a bio-macromolecule isolated from Acanthopanax trifoliatus (L.) Merr and has therapeutic potential for diabetes management due to its anti-hyperglycemia activity.MethodsType 2 diabetes mellitus was induced in mice using streptozotocin, and 40 and 80 mg/kg ATMP was administered daily via the intragastric route for 8 weeks. Food intake, water intake, and body weight were recorded. The fasting blood glucose (FBG), fasting insulin (FINS) and an oral glucose tolerance test (OGTT) were performed. Histological changes in the liver and pancreas were analyzed by H&amp;E staining. The mRNA and the protein levels of key factors involved in glycogen synthesis, glycogenolysis, and gluconeogenesis were measured by quantitative real time PCR and Western blotting.ResultsIn this study, we found that ATMP could effectively improve glucose tolerance and alleviate insulin resistance by promoting insulin secretion and inhibiting glucagon secretion. In addition, ATMP decreases glycogen synthesis by inhibiting PI3K/Akt/GSK3β signaling, reduces glycogenolysis via suppressing cAMP/PKA signaling, and suppresses liver gluconeogenesis by activating AMPK signaling.ConclusionTogether, ATMP has the potential to be developed as a new multitargets therapeutics for type 2 diabetes.
Efficacy and safety of anti-PD-1 antibody plus chemoradiotherapy in locally advanced esophageal squamous cancer
Authors: Ma Ji , Yao Nan , Lu Jiaying , Qu Wanxi , Cui Li , Yuan Shiwang , Li Na , Tong Shaodong , Qin Zhaohui , Yao Yuanhu 
Published: February 2023

ObjectiveTo compare effects and adverse events of anti-programmed cell death protein 1 (anti-PD-1) antibody combined with chemoradiotherapy (CRT) and CRT alone as the initial treatment in locally advanced esophageal squamous cell carcinoma (ESCC).MethodsWe retrospectively reviewed locally advanced ESCC patients who received Anti-PD-1+CRT as initial treatment at 3 institutions. Primary outcomes of interest were progression-free survival (PFS) and overall survival (OS); secondary outcomes were objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and treatment-related adverse events (AEs) including immune-related adverse events (irAEs).ResultsAt data cutoff, 81 patients were included (30 Anti-PD-1+CRT, 51 CRT). Median follow-up was 31.4 months. Anti-PD-1+CRT resulted in significant improvements in PFS (median, 18.6 vs. 11.8 months, HR 0.48 [95% CI, 0.29–0.80], P = 0.008), and OS (median, 27.7 vs. 17.4 months, HR 0.37 [95% CI, 0.22–0.63], P = 0.002), compared with CRT in ESCC. The ORR and DCR of patients treated with Anti-PD-1+CRT were also significantly higher than those treated with CRT (80.0% vs. 56.9%, P = 0.034), (100% vs. 82.4%, P = 0.023), respectively. Anti-PD-1+CRT had better durable response compared with CRT, with DoR (median,17.3 vs. 11.1 months, P = 0.022). Treatment-related adverse event incidence was similar between the two groups (any Grade, 93.3% vs. 92.2%; ≥Grade 3, 50.0% vs. 33.3%).ConclusionAnti-PD-1 plus chemoradiotherapy demonstrated promising antitumor activity and was well tolerated in locally advanced ESCC.
Metabolomic biomarkers for the diagnosis and post-transplant outcomes of AFP negative hepatocellular carcinoma
Authors: Lin Zuyuan , Li Huigang , He Chiyu , Yang Modan , Chen Hao , Yang Xinyu , Zhuo Jianyong , Shen Wei , Hu Zhihang , Pan Linhui , Wei Xuyong , Lu Di , Zheng Shusen , Xu Xiao 
Published: February 2023

BackgroundEarly diagnosis for α-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) remains a critical problem. Metabolomics is prevalently involved in the identification of novel biomarkers. This study aims to identify new and effective markers for AFP negative HCC.MethodsIn total, 147 patients undergoing liver transplantation were enrolled from our hospital, including liver cirrhosis patients (LC, n=25), AFP negative HCC patients (NEG, n=44) and HCC patients with AFP over 20 ng/mL (POS, n=78). 52 Healthy volunteers (HC) were also recruited in this study. Metabolomic profiling was performed on the plasma of those patients and healthy volunteers to select candidate metabolomic biomarkers. A novel diagnostic model for AFP negative HCC was established based on Random forest analysis, and prognostic biomarkers were also identified.Results15 differential metabolites were identified being able to distinguish NEG group from both LC and HC group. Random forest analysis and subsequent Logistic regression analysis showed that PC(16:0/16:0), PC(18:2/18:2) and SM(d18:1/18:1) are independent risk factor for AFP negative HCC. A three-marker model of Metabolites-Score was established for the diagnosis of AFP negative HCC patients with an area under the time-dependent receiver operating characteristic curve (AUROC) of 0.913, and a nomogram was then established as well. When the cut-off value of the score was set at 1.2895, the sensitivity and specificity for the model were 0.727 and 0.92, respectively. This model was also applicable to distinguish HCC from cirrhosis. Notably, the Metabolites-Score was not correlated to tumor or body nutrition parameters, but difference of the score was statistically significant between different neutrophil-lymphocyte ratio (NLR) groups (≤5 vs. &gt;5, P=0.012). Moreover, MG(18:2/0:0/0:0) was the only prognostic biomarker among 15 metabolites, which is significantly associated with tumor-free survival of AFP negative HCC patients (HR=1.160, 95%CI 1.012-1.330, P=0.033).ConclusionThe established three-marker model and nomogram based on metabolomic profiling can be potential non-invasive tool for the diagnosis of AFP negative HCC. The level of MG(18:2/0:0/0:0) exhibits good prognosis prediction performance for AFP negative HCC.
Risk stratification of postoperative cardiopulmonary toxicity after trimodality therapy for esophageal cancer
Authors: Kowalchuk Roman O. , Spears Grant M. , Morris Lindsay K. , Owen Dawn , Yoon Harry H. , Jethwa Krishan , Chuong Michael D. , Ferris Matthew J. , Haddock Michael G. , Hallemeier Christopher L. , Wigle Dennis , Lin Steven H. , Merrell Kenneth W. 
Published: February 2023

Purpose/objectivePostoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes.Materials/methodsPatients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. CPTTB was derived from total perioperative toxicity burden (Lin et al. JCO 2020). To develop a CPTTB risk score predictive for major CPTTB, recursive partitioning analysis was used.ResultsFrom 3 institutions, 571 patients were included. Patients were treated with 3D (37%), IMRT (44%), and proton therapy (19%). 61 patients had major CPTTB (score ≥ 70). Increasing CPTTB was predictive of decreased OS (p&lt;0.001), lengthier post-esophagectomy length of stay (LOS, p&lt;0.001), and death or readmission within 60 days of surgery (DR60, p&lt;0.001). Major CPTTB was also predictive of decreased OS (hazard ratio = 1.70, 95% confidence interval: 1.17-2.47, p=0.005). The RPA-based risk score included: age ≥ 65, grade ≥ 2 nausea or esophagitis attributed to chemoradiation, and grade ≥ 3 hematologic toxicity attributed to chemoradiation. Patients treated with 3D radiotherapy had inferior OS (p=0.010) and increased major CPTTB (18.5% vs. 6.1%, p&lt;0.001).ConclusionCPTTB predicts for OS, LOS, and DR60. Patients with 3D radiotherapy or age ≥ 65 years and chemoradiation toxicity are at highest risk for major CPTTB, predicting for higher short and long-term morbidity and mortality. Strategies to optimize medical management and reduce toxicity from chemoradiation should be strongly considered.