bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary intakes and nutritional issues in inborn errors of immunity: a systematic review
Authors: Freer Macey , Bhatia Rani , Preece Kahn , Pursey Kirrilly M. 
Published: September 2024

IntroductionInborn errors of immunity (IEI) are characterized by an inherited dysregulation or absence of immune system components that can manifest clinically in complications that predispose an individual to feeding difficulties or impaired swallowing, digestion, and absorption. Treatment side-effects or altered requirements may further impair nutritional status. While adequate nutrition is necessary for optimal growth and immune function, little is known about nutritional intakes in IEI, and best practice nutrition guidelines are limited. This review aimed to synthesize current evidence on the dietary intakes, anthropometry and nutritional biochemistry in individuals with an IEI.MethodsA systematic review of literature published from database inception to March 2023 was conducted in accordance with the PRISMA guidelines. Articles eligible for inclusion reported anthropometric, biochemical, or dietary intake-related measures in pediatric or adult patients with a diagnosed IEI. Identified articles were screened for eligibility; data was synthesized descriptively.ResultsA total of 4488 studies were retrieved of which 34 were included. Across studies, 2894 IEI individuals were included (age range 4 weeks to 83y), predominantly focusing on ataxia telangiectasia (AT) and common variable immunodeficiency (CVID). A significant association between inadequate energy intakes and IEI was identified (n=6 studies); however, there was significant variability in adequacy of macro- and micronutrients across studies. Patients with IEI were at risk of malnutrition (range 30% to 70%); although anthropometric assessment measures were not consistent across studies. Biochemical assessments found patients were also at risk of micronutrient deficiencies including vitamin D.DiscussionThis review identified few studies assessing dietary intakes, anthropometry and nutritional biochemistry in patients with IEI, with considerable heterogeneity across studies. Future longitudinal studies using consistent validated dietary assessment tools and anthropometric measures in diverse IEI patient populations are needed. This review reinforces the need for dietetic input in people with an IEI and the development evidence-based clinical practice guidelines for people with an IEI.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412365.
Development of human innate immune responses in a humanized mouse model expressing four human myelopoiesis transgenes
Authors: Stocks Hannah , De Leeuw Elisabeth , Lambrecht Bart N. , Vandekerckhove Linos , van Loo Geert , Wullaert Andy 
Published: September 2024

BackgroundDysregulated innate immune responses underlie multiple inflammatory diseases, but clinical translation of preclinical innate immunity research in mice is hampered by the difficulty of studying human inflammatory reactions in an in vivo context. We therefore sought to establish in vivo human inflammatory responses in NSG-QUAD mice that express four human myelopoiesis transgenes to improve engraftment of a human innate immune system.MethodsWe reconstituted NSG-QUAD mice with human hematopoietic stem and progenitor cells (HSPCs), after which we evaluated human myeloid cell development and subsequent human responses to systemic and local lipopolysaccharide (LPS) challenges.ResultsNSG-QUAD mice already displayed engraftment of human monocytes, dendritic cells and granulocytes in peripheral blood, spleen and liver at 6 weeks after HSPC reconstitution, in which both classical, intermediate and non-classical monocytes were present. These huNSG-QUAD mice responded to intraperitoneal and intranasal LPS challenges with production of NF-κB-dependent human cytokines, a human type I interferon response, as well as inflammasome-mediated production of human IL-1β and IL-18. The latter were specifically abrogated by the NLRP3 inhibitor MCC950, while LPS-induced human monocyte death was not altered. Besides providing proof-of-principle for small molecule testing of human inflammatory reactions in huNSG-QUAD mice, this observation suggests that LPS-induced in vivo release of human NLRP3 inflammasome-generated cytokines occurs in a cell death-independent manner.ConclusionHuNSG-QUAD mice are competent for the NF-κB, interferon and inflammasome effectors of human innate immunity, and can thus be utilized to investigate signaling mechanisms and pharmacological targeting of human inflammatory responses in an in vivo setting.
Dysregulated C1q and CD47 in the aging monkey brain: association with myelin damage, microglia reactivity, and cognitive decline
Authors: DeVries Sarah A. , Dimovasili Christina , Medalla Maria , Moore Tara L. , Rosene Douglas L. 
Published: September 2024

Normal aging, though lacking widespread neurodegeneration, is nevertheless characterized by cognitive impairment in learning, memory, and executive function. The aged brain is spared from neuron loss, but white matter is lost and damage to myelin sheaths accumulates. This myelin damage is strongly associated with cognitive impairment. Although the cause of the myelin damage is not known, microglia dysregulation is a likely contributor. Immunologic proteins interact with microglial receptors to modulate microglia-mediated phagocytosis, which mediates myelin damage clearance and turn-over. Two such proteins, “eat me” signal C1q and “don’t eat me” signal CD47, act in opposition with microglia. Both C1q and CD47 have been implicated in Multiple Sclerosis, a demyelinating disease, but whether they play a role in age-related myelin pathology is currently unknown. The present study investigates C1q and CD47 in relation to age-related myelin degeneration using multilabel immunofluorescence, RNAscope, and confocal microscopy in the cingulum bundle of male and female rhesus monkeys across the lifespan. Our findings showed significant age-related elevation in C1q localized to myelin basic protein, and this increase is associated with more severe cognitive impairment. In contrast, CD47 localization to myelin decreased in middle age and oligodendrocyte expression of CD47 RNA decreased with age. Lastly, microglia reactivity increased with age in association with the changes in C1q and CD47. Together, these results suggest disruption in the balance of “eat me” and “don’t eat me” signals during normal aging, biasing microglia toward increased reactivity and phagocytosis of myelin, resulting in cognitive deficits.
The influence of CRS and ICANS on the efficacy of anti-CD19 CAR-T treatment for B-cell acute lymphoblastic leukemia
Authors: Ma Yuhan , Zhou Hongyuan , Zhang Jiaoli , Zhang Qing , Li Yujie , Xie Ruiyang , Zhang Bingpei , Shen Ziyuan , Li Ping , Liang Aibin , Zhou Keshu , Han Lu , Hu Yongxian , Xu Kailin , Sang Wei , Wang Xiangmin 
Published: September 2024

BackgroundChimeric antigen receptor T-cell (CAR-T) therapy has offered new opportunities for patients with relapsed/refractory B-cell lymphoblastic leukemia (r/r B-ALL). However, cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are the two most common toxicities following CAR-T cell therapy. At present, whether the occurrence of CRS and ICANS will impact CAR-T activity remains unknown; this affects the therapeutic efficacy of CAR-T.MethodsIn this multicenter retrospective study, we enrolled 93 patients with r/r B-ALL receiving anti-CD19 CAR-T cell therapy at four medical centers. We evaluated their complete response (CR) rates, minimal residual disease (MRD)-negative CR rates, and survival outcomes.ResultsAmong the included patients, 76 (81.7%) developed CRS and 16 (5.3%) developed ICANS. Fifteen patients experienced concurrent CRS and ICANS. However, no significant differences were noted in CR or MRD-negative CR rates between patients with and without CRS/ICANS. Furthermore, no significant difference was noted in leukemia-free survival (LFS) (p = 0.869 for CRS and p = 0.276 for ICANS) or overall survival (OS) (p = 0.677 for CRS and p = 0.326 for ICANS) between patients with and without CRS/ICANS. Similarly, patients with concurrent CRS and ICANS exhibited no differences in OS and LFS when compared with other patients. Multivariate analysis showed that the development of CRS and ICANS was not associated with any difference in OS and LFS.ConclusionPatients with CRS/ICANS experience similar clinical outcomes compared with those without CRS/ICANS following anti-CD19 CAR-T therapy.
Umbilical cord blood stem cells as third-party adjuvant infusions in human leukocyte antigen antibody-positive patients undergoing haploidentical hematopoietic stem cell transplantation
Authors: Wang Yuying , Zhao Yiou , Fang Xiaosheng , Yuan Dai , Ding Mei , Lu Kang , Qu Huiting , Wang Na , Lv Xiao , Li Peipei , Zhen Changqing , Xu Hongzhi , Jiang Yujie 
Published: September 2024

IntroductionGraft failure (GF) or poor graft function (PGF) remain critical obstacles in haploidentical hematopoietic stem cell transplantation (haplo-HSCT), especially in recipients with HLA antibodies. Here, we performed a retrospective cohort study to investigate the efficacy and safety of the use of unrelated umbilical cord blood stem cells (UCBs) as a third-party adjuvant infusion in patients with HLA-antibodies undergoing haplo-HSCT.MethodsA total of 90 patients were divided into three groups: 17 patients in Group A (with positive HLA antibodies and who received UCB infusion), 36 patients in Group B (with positive HLA antibodies without UCB infusion), and 37 patients in Group C (without HLA antibody or UCB infusion).ResultsThe median age of patients included in Groups A, B, and C was 43 (IQR, 27 - 49.5), 33 (IQR, 20 - 48.75), and 30 (IQR, 18 - 46.5) years, respectively. All but one patient in Group B achieved granulocyte recovery within 28 days after transplantation. The median time to granulocyte engraftment were all 12 days for patients in Groups A, B, and C, respectively. All the patients in Group A achieved 100% donor chimerism without UCB engraftment. There were no significant differences in granulocyte or platelet engraftment time between the three groups. There were 1, 5, and 0 patients in Groups A, B, and C, respectively, who developed PGF. The cumulative incidence rates for any grade of acute graft-versus-host disease (aGVHD) were comparable among the three groups. Patients in Group B presented a greater incidence of cGVHD than did those in Group A (P = 0.002) and Group C (P = 0.006). Patients in Group A presented more limited and milder cGVHD than those in Group C (P &lt; 0.0001). The 1-year relapse-free survival (RFS) was 70.6% (95% CI, 0.47 - 0.87), 55.6% (95% CI, 0.40 - 0.70), and 77.9% (95% CI, 0.63 - 0.89) in Groups A, B, and C, respectively.DiscussionOur results indicated that patients who were positive for HLA antibodies were at a greater risk of developing GF/PGF. Co-infusion with UCBs was safe and improved engraftment, cGVHD, and improved the 1-year RFS to some extent.
Lanadelumab in a kidney transplant patient with hereditary angioedema due to C1-inhibitor deficiency and high cardiovascular risk - a case report
Authors: Gidaro Antonio , La Cava Leyla , Donadoni Mattia , Popescu Janu Valentina , Cogliati Chiara , Brucato Antonio Luca , Zanichelli Andrea , Cancian Mauro , Bizzi Emanuele 
Published: September 2024

IntroductionCardiovascular pathologies represent the first cause of death in uremic patients and are among the leading causes of mortality in patients with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH). Before 2020, the most common treatment for long-term prophylaxis in HAE-C1INH patients in Italy was attenuated androgen, which may increase cardiovascular risk by multiple mechanisms.Case descriptionWe present a case report of a 56-year-old patient with HAE-C1INH type I affected by IgA nephropathy with severe kidney impairment. The patient experienced a first kidney transplant and, after late rejection, underwent a second kidney transplant. Further comorbidities included obesity, hypertensive cardiomyopathy, HCV liver disease, and dyslipidemia. His prophylactic therapy to prevent angioedema attacks had consisted of attenuated androgens for about 40 years. Since 2020, new modern targeted therapy for LTP, particularly lanadelumab, has shown promising results. The majority of patients with attenuated androgens have been successfully switched to lanadelumab, including our patient. Since introducing lanadelumab (300 mg subcutaneously every two weeks; after a six-month attack-free period, the dosing interval of lanadelumab was extended to four weeks), the patient has not experienced any acute HAE attack and did not report any adverse events. Moreover, we observed decreased total cholesterol, C-LDL, and body mass index, reducing the Matsushita et al. score for ten years of cardiovascular risk from 13.2% to 9.3%.Conclusionlanadelumab is effective and safe in preventing hereditary angioedema attacks, as well as in reducing cardiovascular risk in an immunosuppressed patient with significant comorbidities. The successful outcomes of this case highlight the potential of lanadelumab as a promising prophylactic therapy.
Promoting coping competence for psychological stressors in nursing training: a controlled pedagogical intervention
Authors: Warwas Julia , Krebs Philine , Vorpahl Wiebke , Weyland Ulrike , Wilczek Larissa , Seeber Susan , Wittmann Eveline 
Published: September 2024

BackgroundMultiple stressors as well as health-and quality-impairing effects of strain in the nursing profession require the systematic acquisition of competence in dealing with these demands, starting at the stage of initial vocational training. This study investigates whether an instructional design, which merges didactic principles of nursing education with concepts and training measures from stress psychology, promotes the acquisition of stress coping competence more effectively than regular teaching on the relevant curricular field at nursing schools.MethodsThe quasi-experimental study design, based on the Solomon four-group plan, included 332 trainees in Germany. The assessment of stress coping competence at the beginning and at the end of the intervention provided a video-stimulated situational judgment test covering nursing-specific stressful situations. All were validated by field experts. Complementing group comparisons, regression analyses examined intervention effects at the individual level while controlling for other predictors of learning success.ResultsThe highest solution rates for the two basic dimensions of stress coping competence, i.e., (1) situation assessment and (2) strategy selection and justification, occurred in the treatment classes without a pretest. At the individual level, treatment effects were confirmed for the first dimension. Students with a migration background showed lower competence gains than other students.ConclusionThe instructional design and the competence test provide valuable foundations for promoting and for diagnosing coping skills. Nevertheless, subsequent studies should examine adaptive support for different learner groups. Furthermore, additional observational phases should focus on the deliberate practice of acquired coping strategies in the practical training settings of nursing education.
Development of prognostic models for advanced multiple hepatocellular carcinoma based on Cox regression, deep learning and machine learning algorithms
Authors: Shen Jie , Zhou Yu , Pei Junpeng , Yang Dashuai , Zhao Kailiang , Ding Youming 
Published: September 2024

BackgroundMost patients with multiple hepatocellular carcinoma (MHCC) are at advanced stage once diagnosed, so that clinical treatment and decision-making are quite tricky. The AJCC-TNM system cannot accurately determine prognosis, our study aimed to identify prognostic factors for MHCC and to develop a prognostic model to quantify the risk and survival probability of patients.MethodsEligible patients with HCC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and then prognostic models were built using Cox regression, machine learning (ML), and deep learning (DL) algorithms. The model’s performance was evaluated using C-index, receiver operating characteristic curve, Brier score and decision curve analysis, respectively, and the best model was interpreted using SHapley additive explanations (SHAP) interpretability technique.ResultsA total of eight variables were included in the follow-up study, our analysis identified that the gradient boosted machine (GBM) model was the best prognostic model for advanced MHCC. In particular, the GBM model in the training cohort had a C-index of 0.73, a Brier score of 0.124, with area under the curve (AUC) values above 0.78 at the first, third, and fifth year. Importantly, the model also performed well in test cohort. The Kaplan–Meier (K-M) survival analysis demonstrated that the newly developed risk stratification system could well differentiate the prognosis of patients.ConclusionOf the ML models, GBM model could predict the prognosis of advanced MHCC patients most accurately.
Research trends between childhood obesity and gut microbiota: a bibliometric analysis (2002–2023)
Authors: Wang Mengping , Zhang Zhen , Liu Yuxuan , Jian Enlin , Ye Peng , Jiang Hongjie , Yu Xiaoping , Cai Peiling 
Published: September 2024

BackgroundIn recent years, the prevalence of childhood obesity has escalated alarmingly, posing significant threats to the physical and mental well-being of children, with an elevated likelihood of persisting into adulthood. Notably, recent investigations have uncovered a profound association between intestinal microbiota, a crucial component of the internal milieu, and childhood obesity. Disturbances in intestinal microbiota and their by-products are now understood to be profoundly intertwined with the evolutionary pathway of childhood obesity. Bibliometric analysis offers a deep understanding of the current research landscape, so we apply it to a review of the emerging trends and patterns between childhood obesity and gut microbiota.Materials and methodsWe conducted a rigorous and extensive search of the Web of Science (WoS) Core Collection database, spanning the years from 1900 to 2023, to analyze scholarly articles pertaining to childhood obesity and gut microbiota. Utilizing VOSviewer, CiteSpace, the R package “bibliometrix,” and the online bibliometric analysis platform (https://bibliometric.com/), we delved into the intricate details of research hotspots, academic collaborations, and emerging trends within this domain.ResultsThe exhaustive search encompassed the globe, uncovering a cumulative total of 1,384 pertinent studies originating from 429 nations. The results were compelling, revealing a profound influence exerted by the United States and China in this specific field of research. Furthermore, it was observed that the volume of scholarly works pertaining to childhood obesity and gut microbiota is steadily growing year on year. The current hot topics in this field include “abuse,” “maltreatment,” “adverse childhood experiences,” “students,” and “food addiction”.ConclusionThis comprehensive review offers a meticulous exploration of the evolving trends and emerging research agendas pertaining to childhood obesity and gut microbiota over the past two decades. It strives to equip researchers with a thorough understanding of the key nations, institutions, journals, and potential collaborators in these specialized fields. Additionally, it sheds light on the current frontiers of research and strategic avenues for further exploration, thus serving as an invaluable resource for scholars delving deeper into the intricacies of childhood obesity and the gut microbiome.
Iron overload regulates cognitive function in rats with minimal hepatic encephalopathy by inducing an increase in frontal butyrylcholinesterase activity
Authors: Lan Hua , Yang Xuhong , Wang Minxing , Wang Minglei , Huang Xueying , Wang Xiaodong 
Published: September 2024

Background and aimsThis study aimed to investigate the effect of iron overload on acetylcholinesterase activity in the frontal lobe tissue of rats with minimal hepatic encephalopathy (MHE) and its relation to cognitive ability. By elucidating the potential mechanisms of cognitive impairment, this study may offer insights into novel therapeutic targets for MHE.Materials and methodsTwelve Sprague-Dawley rats were purchased and randomly assigned to either the experimental or control group with six rats in each group. Following the induction of MHE, the Morris Water Maze (MWM) was utilized to assess spatial orientation and memory capacity. Subsequently, Magnetic Resonance Imaging (MRI) scans were performed to capture Quantitative Susceptibility Mapping (QSM) images of all rats' heads.ResultsCompared to the control group rats, the MHE model rats showed significantly reduced learning and memory capabilities as well as spatial orientation abilities (P &lt; 0.05). Furthermore, the susceptibility values in the frontal lobe tissue of MHE model rats was significantly higher than that of the control group rats (P &lt; 0.05), and the corresponding BuChE activity in the frontal lobe extract of model rats was significantly increased while BuChE activity in the peripheral blood serum was significantly decreased compared to the control group rats (P &lt; 0.05). Meanwhile, our findings indicate a significant positive correlation between latency period and BuChE activity with susceptibility values in the MHE group.ConclusionThe changes in BuChE activity in frontal lobe extract may be related to changes in spatial orientation and behavioral changes in MHE, and iron overload in the frontal lobe tissue may regulate changes in BuChE activity, BuChE levels appear to be iron-dependent.
Causal associations of white blood cell count and sudden sensorineural hearing loss: a bidirectional and multivariable Mendelian randomization study
Authors: Zhang Ling , Chen Jialei , Zhong Shixun , Luo Jing , Tang Ping 
Published: September 2024

BackgroundNumerous compelling observational studies have demonstrated a plausible correlation between the white blood cell count and the susceptibility to sudden sensorineural hearing loss (SSNHL). Nevertheless, the exact causal relationship between these two factors remains ambiguous. The objective of our study was to assess the causal impact of white blood cell count on sudden sensorineural hearing loss through the implementation of a bidirectional and multivariable Mendelian randomization (MR) methodology.MethodsGenetic data pertaining to white blood cell count were acquired from the Blood Cell Consortium, encompassing a total of 563,946 subjects. Concurrently, summary data on sudden sensorineural hearing loss were sourced from a Genome-Wide Association Study (GWAS), involving 196,592 participants, comprising 1,491 cases and 195,101 controls. The primary method employed for MR analysis was the Inverse Variance Weighted method (IVW), while sensitivity analysis utilized the Weighted Median method, MR-Egger method, and MR-PRESSO method.ResultsIn IVW method, genetically predicted elevated lymphocyte cell count demonstrates an effective reduction in the risk of sudden sensorineural hearing loss (odds ratio = 0.747, 95% CI = 0.565–0.987, p = 0.04). These findings remain consistent in multivariate MR analysis, even after adjusting for monocyte cell count and neutrophil cell count levels (odds ratio = 0.929, 95% CI = 0.867–0.995, p = 0.036). However, there is no discernible evidence supporting a direct causal relationship between monocyte cell count and neutrophil cell count levels and the occurrence of SSNHL.ConclusionWithin the normal range, higher lymphocyte cell count levels exhibit a potential protective effect against SSNHL. Meanwhile, no direct causal relationship are identified between monocyte cell count and neutrophil cell count levels and the risk of SSNHL.