bluuebunny/crossref_metadata_2025_split huggingface dataset:
Third SARS-CoV-2 vaccination and breakthrough infections enhance humoral and cellular immunity against variants of concern
Authors: Ruhl Louisa , Kühne Jenny F. , Beushausen Kerstin , Keil Jana , Christoph Stella , Sauer Jasper , Falk Christine S. 
Published: March 2023

IntroductionSARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections.MethodsPeripheral blood samples of n=20 individuals were analyzed in the time course of three SARS-CoV-2 vaccinations and/or breakthrough infection. S1-, RBD-, S2- and N-specific IgG antibodies were quantified using Luminex-based multiplex assays and electrochemiluminescence multiplex assays for surrogate neutralization in plasma. Changes in cellular immune components were determined via flow cytometry of whole blood samples.ResultsAll individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron BA.1 independently of age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to the appearance of new variant-specific antibodies.DiscussionIn conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants, and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.
Elevated LDL-C, high blood pressure, and low peak V̇O2 associate with platelet mitochondria function in children—The Arkansas Active Kids Study
Authors: Diaz Eva C. , Adams Sean H. , Weber Judith L. , Cotter Matthew , Børsheim Elisabet 
Published: March 2023

Purpose: To evaluate the association of platelet (PL) mitochondria respiration with markers of cardiovascular health in children ages 7–10 years.Methods: PL mitochondrial respiration (n = 91) was assessed by high resolution respirometry (HRR): Routine (R) respiration, complex (C) I linked respiration (CI), and maximal uncoupled electron transport capacity of CII (CIIE) were measured. The respiratory control ratio (RCR) was calculated as the ratio of maximal oxidative phosphorylation capacity of CI and CI leak respiration (PCI/LCI). Peak V.O2 (incremental bike test) and body composition (dual-energy X-ray absorptiometry) were measured. Multiple generalized linear regression analysis was used to model the association of measures by HRR with variables of interest: adiposity, low-density lipoprotein (LDL-C) and triglyceride (TG) status (normal vs. elevated) HOMA2-IR, blood pressure status (normal vs. high), and demographics.Results: R and CI-linked respiration positively associated with adiposity, high blood pressure (HBP), and peak V.O2. R and CI-linked respiration had inverse association with age and elevated LDL-C. CIIE was higher in children with elevated LDL-C (log-β = −0.54, p = 0.010). HBP and peak V.O2 interacted in relation to RCR (log-β = −0.01, p = 0.028). Specifically, RCR was lowest among children with HBP and low aerobic capacity (i.e., mean peak V.O2 -1SD). HOMA2-IR did not associate with measures of PL mitochondria respiration.Conclusion: In PL, R and CI-linked mitochondrial respiration directly associate with adiposity, peak V.O2 and HBP. Elevated LDL-C associates with lower CI-linked respiration which is compensated by increasing CII respiration. PL bioenergetics phenotypes in children associate with whole-body metabolic health status.
A preliminary study of diffusion tensor imaging in root entry zone of primary trigeminal neuralgia
Authors: Wang Yiwen , Wang Danni , Wu Yingwei , Zhu Ce , Wei Wenbin , Li Yao , Li Lingzhi , Chen Wantao , Chen Minjie 
Published: March 2023

ObjectivePrimary Trigeminal Neuralgia (PTN) is a common and refractory neurological disease. Conventional vascular compression theory could not completely explain the etiology and pathogenesis of PTN. This study used diffusion tensor imaging (DTI) to demonstrate the microstructural changes of root entry zone (REZ) region in PTN patients.Materials and methodsDTI sequences was performed on PTN patients and healthy controls (HCs). Clinical data included affected side, disease course and visual analogue scale (VAS) were collected. Quantitative DTI variables such as FA, MD, AD and RD of the root entry/Exit zone (REZ) were measured and compared in PTN/HCs, affected/unaffected side, and pre/post operation groups. The PCoA was established to conduct overall differences between PTN group and the HCs.ResultsA total of 17 patients with PTN (mean age 59.29 ± 8.53; 5 men) and 34 HCs (mean age 57.70 ± 6.37; 10 men) were included. Lower FA value of the affected side of PTN group was observed compared to the unaffected side and the HCs (p = 0.001), whereas the values of MD, AD and RD were significantly increased (p &lt; 0.001). Moreover, the decrease of FA value was recovered post operation. PCoA results of the comprehensive indexes can significantly distinguish PTN group from HCs (r = 0.500, p &lt; 0.001).ConclusionQuantitative variables derived from DTI in REZ had significantly different profiles between PTN patients and HCs, which were associated with VAS situation and the disease course of PTN. The comprehensive index established on DTI variables were of great potential to reveal the microstructure changes in PTN patients and predict the therapeutic effect.
An in vitro model of drug-resistant seizures for selecting clinically effective antiseizure medications in Febrile Infection-Related Epilepsy Syndrome
Authors: Cerovic Milica , Di Nunzio Martina , Craparotta Ilaria , Vezzani Annamaria 
Published: March 2023

IntroductionFIRES is a rare epileptic encephalopathy induced by acute unremitting seizures that occur suddenly in healthy children or young adults after a febrile illness in the preceding 2 weeks. This condition results in high mortality, neurological disability, and drug-resistant epilepsy. The development of new therapeutics is hampered by the lack of validated experimental models. Our goal was to address this unmet need by providing a simple tool for rapid throughput screening of new therapies that target pathological inflammatory mechanisms in FIRES. The model was not intended to mimic the etiopathogenesis of FIRES which is still unknown, but to reproduce salient features of its clinical presentation such as the age, the cytokine storm and the refractoriness of epileptic activity to antiseizure medications (ASMs).MethodsWe refined an in vitro model of mouse hippocampal/temporal cortex acute slices where drug-resistant epileptic activity is induced by zero Mg2+/100 μM 4-aminopirydine. Clinical evidence suggests that acute unremitting seizures in FIRES are promoted by neuroinflammation triggered in the brain by the preceding infection. We mimicked this inflammatory component by exposing slices for 30 min to 10 μg/ml lipopolysaccharide (LPS).ResultsLPS induced a sustained neuroinflammatory response, as shown by increased mRNA levels of IL-1β, CXCL1 (IL-8), TNF, and increased IL-1β/IL-1Ra ratio. Epileptiform activity was exacerbated by neuroinflammation, also displaying increased resistance to maximal therapeutic concentrations of midazolam (100 μM), phenytoin (50 μM), sodium valproate (800 μM), and phenobarbital (100 μM). Treatment of LPS-exposed slices with two immunomodulatory drugs, a mouse anti-IL-6 receptor antibody (100 μM) corresponding to tocilizumab in humans, or anakinra (1.3 μM) which blocks the IL-1 receptor type 1, delayed the onset of epileptiform events and strongly reduced the ASM-resistant epileptiform activity evoked by neuroinflammation. These drugs were shown to reduce ASM-refractory seizures in FIRES patients.DiscussionThe neuroinflammatory component and the pharmacological responsiveness of epileptiform events provide a proof-of-concept validation of this in vitro model for the rapid selection of new treatments for acute ASM-refractory seizures in FIRES.
Effect of switching to erenumab in non-responders to a CGRP ligand antibody treatment in migraine: A real-world cohort study
Authors: Overeem Lucas Hendrik , Lange Kristin Sophie , Fitzek Mira Pauline , Siebert Anke , Steinicke Maureen , Triller Paul , Hong Ja Bin , Reuter Uwe , Raffaelli Bianca 
Published: March 2023

BackgroundTherapeutic options for migraine prevention in non-responders to monoclonal antibodies (mAbs) targeting Calcitonin Gene-Related Peptide (CGRP) and its receptor are often limited. Real-world data have shown that non-responders to the CGRP-receptor mAb erenumab may benefit from switching to a CGRP ligand mAb. However, it remains unclear whether, vice versa, erenumab is effective in non-responders to CGRP ligand mAbs. In this study, we aim to assess the efficacy of erenumab in patients who have previously failed a CGRP ligand mAb.MethodsThis monocentric retrospective cohort study included patients with episodic or chronic migraine in whom a non-response (&lt; 30% reduction of monthly headache days during month 3 of treatment compared to baseline) to the CGRP ligand mAbs galcanezumab or fremanezumab led to a switch to erenumab, and who had received at least 3 administrations of erenumab. Monthly headache days were retrieved from headache diaries to assess the ≥30% responder rates and the absolute reduction of monthly headache days at 3 and 6 months of treatment with erenumab in this cohort.ResultsFrom May 2019 to July 2022, we identified 20 patients who completed 3 months of treatment with erenumab after non-response to a CGRP ligand mAb. Fourteen patients continued treatment for ≥6 months. The ≥30% responder rate was 35% at 3 months, and 45% at 6 months of treatment with erenumab, respectively. Monthly headache days were reduced from 18.6 ± 5.9 during baseline by 4.1 ± 3.1 days during month 3, and by 7.0 ± 4.8 days during month 6 compared to the month before treatment with erenumab (p&lt; 0.001, respectively). Responders and non-responders to erenumab did not differ with respect to demographic or headache characteristics.ConclusionSwitching to erenumab in non-responders to a CGRP ligand mAb might be beneficial in a subgroup of resistant patients, with increasing responder rates after 6 months of treatment. Larger prospective studies should aim to predict which subgroup of patients benefit from a switch.
Effects of relative humidity, surface area and production route on hydrogen yields from water on the surface of plutonium dioxide
Authors: Webb Kevin , Gregson Colin , Holt Josh , McLuckie Bliss , Orr Robin , Sims Howard , Woodhead David , Hobbs Jeff , Steele Helen , Currell Fred , Jones Luke , Pimblott Simon , Taylor Robin 
Published: March 2023

Over 60 samples of plutonium dioxide (PuO2) powders of varying provenance have been exposed to humid atmospheres and the hydrogen (H2) generation rates measured by gas chromatography. The effects of relative humidity (RH), specific surface area (SSA), plutonium isotopic composition (absorbed dose), and overlying atmosphere have been investigated for ‘as received’ PuO2 powders from the United Kingdom’s Thorp and Magnox reprocessing plants, high surface area powder produced in the laboratory and Magnox PuO2 that was recalcined at 800, 900 or 950°C. Hydrogen generation was shown to be susceptible to subtle influences with the most consistent results observed at 95% RH. However, it was shown that the measured (net) hydrogen decreases with decreasing RH and with atmosphere in the order: Air &gt; argon &gt; nitrogen. There was no clear effect of SSA, apart from with the highest SSA samples (∼40 m2.g−1) but these powders also have very different morphology, porosity, and carbon content to the rest. The results presented substantially enhance the growing body of literature on the factors that determine hydrogen and gas generation from PuO2 that has significant implications for long term safe storage of plutonium globally.
Neurological impairment and malnutrition in children: The role of home enteral nutrition in real life
Authors: Diamanti Antonella , Capriati Teresa , Mosca Antonella , Trovato Chiara Maria , Laureti Francesca , Mazzoli Bianca , Bolasco Giulia , Caldaro Tamara , De Peppo Francesco , Staccioli Susanna , Papa Raffaele Edo , Cerchiari Antonella , De Angelis Paola , Maggiore Giuseppe 
Published: March 2023

ObjectiveRecent decades have brought an increased survival of children with Neurologic Impairment (NI) but malnutrition and digestive comorbidity remain important challenges to face. We designed the present study to assess the course of nutritional status following standardized Home Enteral Nutrition (HEN) program and to evaluate impact of changing mode of feeding, as a part of overall multidisciplinary management, on digestive co-morbidity as Gastro-Esophageal Reflux Disease (GERD), Oropharyngeal Dysphagia (OPD), constipation and airway aspiration.MethodsWe performed a retrospective analysis on NI children entered into Institutional HEN program due to NI disorders between January 2011 and 2019. Demographic, anthropometric characteristics (BMI z-score and weight for age z-score) and symptoms (GERD, OPD constipation and airway aspiration) were collected at the enrolment and during the follow up.ResultsWe enrolled 402 patients (median age: 39 months); overall survival was 97%. Nutritional status was significantly improved by HEN; in particular growth profile significantly changed within the first 2 years following HEN beginning; GERD and airways aspirations decreased after HEN beginning. Constipation and OPD remained unchanged over time.ConclusionsMalnutrition and digestive complaints are distinctive features of NI children. Nutritional status improve after 2 years from the beginning of standardized nutritional interventions. Overall multidisciplinary care, including standardized HEN protocols, seems to also impact on GERD and airway aspirations, which can decrease over time. It is possible that constipation and OPD, unchanged over time, are more dependent on underlying diseases than on overall treatments.
Immune microenvironment and clinical feature analyses based on a prognostic model in lymph node-positive breast cancer
Authors: Lu Nannan , Fu Changfang , Zhang Lei , You Yangyang , Li Xiang , Zhang Qian , Wang Pin , Han Xinghua 
Published: March 2023

BackgroundIf lymph node metastasis occurs in breast cancer patients, the disease can progress rapidly. Based on the infiltrative immune cells of breast cancer patients with lymph node positivity, we constructed the LNPRS for selecting prognostic predictors.MethodsThe LNPRS was established and the predictive value of the LNPRS was verified by independent testing cohorts. A nomogram was also established to confirm the therapeutic guidance significance of the LNPRS. The correlation of the LNPRS with tumor mutation burden, immune microenvironment score, immune checkpoints, the proportion of tumor-infiltrating immune cells, and GSEA and GSVA enrichment pathways were also evaluated.ResultsIn the training cohort, the overall survival of breast cancer patients who had high LNPRS was shorter than that of patients who had low LNPRS (7.98 years versus 20.42 years, P-value&lt; 8.16E-11). The AUC values for 5-, 10-, and 15-years were 0.787, 0.739, and 0.800, respectively. The ability to predict prognosis for the LNPRS was also tested in 3 independent testing cohorts. Furthermore, the predictive value of the LNPRS for chemotherapy and immunotherapy was also proven. The GSEA and GSVA showed that the LNPRS was closely related to the activation of T and B lymphocytes and IFN-γ secretion. Moreover, breast cancer patients with low LNPRS had higher TME scores than those with high LNPRS.ConclusionWe can conclude that the LNPRS is a robust prognostic biomarker in breast cancer patients with positive lymph nodes and may be helpful for patients to make a clinical decision.
The combination of radiomics features and VASARI standard to predict glioma grade
Authors: You Wei , Mao Yitao , Jiao Xiao , Wang Dongcui , Liu Jianling , Lei Peng , Liao Weihua 
Published: March 2023

Background and PurposeRadiomics features and The Visually AcceSAble Rembrandt Images (VASARI) standard appear to be quantitative and qualitative evaluations utilized to determine glioma grade. This study developed a preoperative model to predict glioma grade and improve the efficacy of clinical strategies by combining these two assessment methods.Materials and MethodsPatients diagnosed with glioma between March 2017 and September 2018 who underwent surgery and histopathology were enrolled in this study. A total of 3840 radiomic features were calculated; however, using the least absolute shrinkage and selection operator (LASSO) method, only 16 features were chosen to generate a radiomic signature. Three predictive models were developed using radiomic features and VASARI standard. The performance and validity of models were evaluated using decision curve analysis and 10-fold nested cross-validation.ResultsOur study included 102 patients: 35 with low-grade glioma (LGG) and 67 with high-grade glioma (HGG). Model 1 utilized both radiomics and the VASARI standard, which included radiomic signatures, proportion of edema, and deep white matter invasion. Models 2 and 3 were constructed with radiomics or VASARI, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.937 and 0.831, respectively, which was less than that of Model 1, with an AUC of 0.966.ConclusionThe combination of radiomics features and the VASARI standard is a robust model for predicting glioma grades.
Circulating tumor cells in peripheral blood as a diagnostic biomarker of breast cancer: A meta-analysis
Authors: Jin Tao , Chen Yao , Chen Qing-Yan , Xiong Yang , Yang Ji-Qiao 
Published: March 2023

PurposeStudies have reported that breast cancer (BC) patients’ circulating tumor cells (CTCs) have varying results for their diagnostic role. Thus, we conducted a meta-analysis to systematically assess the accuracy of CTCs in the diagnosis of BC.MethodsA meta-analysis was conducted to evaluate the overall accuracy of CTC detection. A pooled analysis of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) was used to measure diagnostic accuracy. In addition, the area under the summary receiver operating characteristic curve (AUC) was used to discriminate BC from non-BC. An analysis of the threshold effect was calculated using the Spearman correlation coefficient. We calculated the Q and I2 statistics to determine whether the studies were heterogeneous. Sensitivity analysis was performed by removing studies one by one. Publication bias was assessed by Deeks’ funnel plot asymmetry test.ResultsStudies from the PubMed, Cochrane Library, Embase, Web of Science, Wanfang, Vip, and CNKI databases were collected for diagnosing BC from January 2000 to April March 2023. Finally, 8 publications were retrieved in total containing 2014 cases involved in the study. Based on a random-effects model, it was found that the pooled SEN was 0.69 (0.55 - 0.80), SPE was 0.93 (0.60 - 0.99), PLR was 9.5 (1.4 - 65.9), NLR was 0.33 (0.23 - 0.48), DOR was 29 (4 - 205) and the AUC of the summary receiver operating characteristic (SROC) curve was 0.81 (0.77 - 0.84). Some heterogeneity was found in the article, but there was no threshold effect to account for it (P = 0.27). Deek’s funnel plot asymmetry test indicated that no publication bias was observed in this meta-analysis (P = 0.52).ConclusionThe results of this meta-analysis confirmed that CTCs were an important component of noninvasive methods of confirming BC with SEN of 0.69 (0.55 - 0.80), SPE of 0.93 (0.60 - 0.99) and AUC of 0.81 (0.77 - 0.84).
Clinical practice guidelines for neonatal hypoxic-ischemic encephalopathy: A systematic review using the appraisal of guidelines for research and evaluation (AGREE) II instrument
Authors: Amer Yasser S. , Anabrees Jasim , Abdelmawla Mohamed , Abdalgader Ayman , Almazroei Asmaa , Alhifzi Ibrahim , AlOnazi Abdullah Hawash , Sabr Yasser , Hneiny Layal , El-Malky Ahmed , Alshalawi Ayesha , Alayoubi Ahmed , Chaudhry Iftikhar A. , Elkhateeb Omar 
Published: March 2023

Background and ObjectiveTo systematically review, critically appraise the quality of recent clinical practice guidelines (CPGs) for neonatal hypoxic ischemic encephalopathy (HIE), and map their recommendations.Data SourcesCPG databases (GIN, ECRI, NICE, SIGN, DynaMed), Bibliographic databases (PubMed, Embase, CINAHL), and related specialized professional societies (e.g., AAP, CPS, BAPM, RCPCH, and SNS).Study SelectionOriginal de-novo developed evidence-based CPGs for HIE, group authorship, Arabic or English languages, and international or national scope. The systematic review was drafted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and Johnston et al methodological guide.Data ExtractionQuality assessment of the included HIE CPGs by the Appraisal of Guidelines for REsearch &amp; Evaluation II (AGREE II) Instrument and report their characteristics, AGREE II ratings, and recommendationsData SynthesisOur search retrieved 2,489 citations, of which two recent HIE CPGs were eligible and appraised: Canadian Paediatric Society (CPS) and Queensland Maternity and Neonatal Services (QMN). The overall assessment of the QMN CPG was superior (83%). Domain 1 (Scope &amp; Purpose) scored (47%, 63%), Domain 2 (Stakeholder Involvement) (72%, 39%), Domain 3 (Rigour of Development) (48%, 43%), Domain 4 (Clarity &amp; Presentation) (100%, 96%), Domain 5 (Applicability) (59%, 9%), and Domain 6 (Editorial Independence) (67%, 17%) for the QMN and CPS CPGs respectively. All appraisers recommended the QMN CPG for use in practice.ConclusionThe methodological quality of the QMN CPG was superior with the relevant recommendations for its use in neonatal practice.Limitationslimited to Arabic and English languages.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=258291, identifier: CRD42021258291.