bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary Immunodeficiency in Children With Autoimmune Cytopenias: Retrospective 154-Patient Cohort
Authors: Westermann-Clark Emma , Meehan Cristina Adelia , Meyer Anna K. , Dasso Joseph F. , Amre Devendra , Ellison Maryssa , Patel Bhumika , Betensky Marisol , Hauk Charles Isaac , Mayer Jennifer , Metts Jonathan , Leiding Jennifer W. , Sriaroon Panida , Kumar Ambuj , Ayala Irmel , Walter Jolan E. 
Published: April 2021

BackgroundPrimary immunodeficiency is common among patients with autoimmune cytopenia.ObjectiveThe purpose of this study is to retrospectively identify key clinical features and biomarkers of primary immunodeficiency (PID) in pediatric patients with autoimmune cytopenias (AIC) so as to facilitate early diagnosis and targeted therapy.MethodsElectronic medical records at a pediatric tertiary care center were reviewed. We selected 154 patients with both AIC and PID (n=17), or AIC alone (n=137) for inclusion in two cohorts. Immunoglobulin levels, vaccine titers, lymphocyte subsets (T, B and NK cells), autoantibodies, clinical characteristics, and response to treatment were recorded.ResultsClinical features associated with AIC-PID included splenomegaly, short stature, and recurrent or chronic infections. PID patients were more likely to have autoimmune hemolytic anemia (AIHA) or Evans syndrome than AIC-only patients. The AIC-PID group was also distinguished by low T cells (CD3 and CD8), low immunoglobulins (IgG and IgA), and higher prevalence of autoantibodies to red blood cells, platelets or neutrophils. AIC diagnosis preceded PID diagnosis by 3 years on average, except among those with partial DiGeorge syndrome. AIC-PID patients were more likely to fail first-line treatment.ConclusionsAIC patients, especially those with Evans syndrome or AIHA, should be evaluated for PID. Lymphocyte subsets and immune globulins serve as a rapid screen for underlying PID. Early detection of patients with comorbid PID and AIC may improve treatment outcomes. Prospective studies are needed to confirm the diagnostic clues identified and to guide targeted therapy.
Rhinovirus C Infection Induces Type 2 Innate Lymphoid Cell Expansion and Eosinophilic Airway Inflammation
Authors: Rajput Charu , Han Mingyuan , Ishikawa Tomoko , Lei Jing , Goldsmith Adam M. , Jazaeri Seyedehzarifeh , Stroupe Claudia C. , Bentley J. Kelley , Hershenson Marc B. 
Published: April 2021

Rhinovirus C (RV-C) infection is associated with severe asthma exacerbations. Since type 2 inflammation is an important disease mechanism in asthma, we hypothesized that RV-C infection, in contrast to RV-A, preferentially stimulates type 2 inflammation, leading to exacerbated eosinophilic inflammation. To test this, we developed a mouse model of RV-C15 airways disease. RV-C15 was generated from the full-length cDNA clone and grown in HeLa-E8 cells expressing human CDHR3. BALB/c mice were inoculated intranasally with 5 x 106 ePFU RV-C15, RV-A1B or sham. Mice inoculated with RV-C15 showed lung viral titers of 1 x 105 TCID50 units 24 h after infection, with levels declining thereafter. IFN-α, β, γ and λ2 mRNAs peaked 24-72 hrs post-infection. Immunofluorescence verified colocalization of RV-C15, CDHR3 and acetyl-α-tubulin in mouse ciliated airway epithelial cells. Compared to RV-A1B, mice infected with RV-C15 demonstrated higher bronchoalveolar eosinophils, mRNA expression of IL-5, IL-13, IL-25, Muc5ac and Gob5/Clca, protein production of IL-5, IL-13, IL-25, IL-33 and TSLP, and expansion of type 2 innate lymphoid cells. Analogous results were found in mice treated with house dust mite before infection, including increased airway responsiveness. In contrast to Rorafl/fl littermates, RV-C-infected Rorafl/flIl7rcre mice deficient in ILC2s failed to show eosinophilic inflammation or mRNA expression of IL-13, Muc5ac and Muc5b. We conclude that, compared to RV-A1B, RV-C15 infection induces ILC2-dependent type 2 airway inflammation, providing insight into the mechanism of RV-C-induced asthma exacerbations.
Factors Predicting the Presence of Maternal Cells in Cord Blood and Associated Changes in Immune Cell Composition
Authors: Haddad Marina El , Karlmark Karlin R. , Donato Xavier-Côme , Martin Gabriel V. , Bretelle Florence , Lesavre Nathalie , Cocallemen Jean-François , Martin Marielle , Picard Christophe , Roudier Jean , Desbriere Raoul , Lambert Nathalie C. 
Published: April 2021

BackgroundCord blood (CB) samples are increasingly used as a source of hematopoietic stem cells in transplantation settings. Maternal cells have been detected in CB samples and their presence is associated with a better graft outcome. However, we still do not know what influences the presence of maternal microchimerism (MMc) in CB samples and whether their presence influences CB hematopoietic cell composition.Patients and MethodsHere we test whether genetic, biological, anthropometric and/or obstetrical parameters influence the frequency and/or quantity of maternal Mc in CB samples from 55 healthy primigravid women. Mc was evaluated by targeting non-shared, non-inherited Human Leukocyte Antigen (HLA)-specific real-time quantitative PCR in whole blood and four cell subsets (T, B lymphocytes, granulocytes and/or hematopoietic progenitor cells). Furthermore CB samples were analyzed for their cell composition by flow cytometry and categorized according to their microchimeric status.ResultsMMc was present in 55% of CB samples in at least one cell subset or whole blood, with levels reaching up to 0.3% of hematopoietic progenitor cells. Two factors were predictive of the presence of MMc in CB samples: high concentrations of maternal serological Pregnancy-Associated-Protein-A at first trimester of pregnancy (p=0.018) and feto-maternal HLA-A and/or –DR compatibility (p=0.009 and p=0.01 respectively). Finally, CB samples positive for MMc were significantly enriched in CD56+ cells compared to CB negative for MMc.ConclusionsWe have identified two factors, measurable at early pregnancy, predicting the presence of maternal cells in CB samples at delivery. We have shown that MMc in CB samples could have an influence on the hematopoietic composition of fetal cells. CD56 is the phenotypic marker of natural killer cells (NK) and NK cells are known to be the main effector for graft versus leukemia reactions early after hematopoietic stem cell transplantation. These results emphasize the importance of MMc investigation for CB banking strategies.
The Synergistic Effects of Polysaccharides and Ginsenosides From American Ginseng (Panax quinquefolius L.) Ameliorating Cyclophosphamide-Induced Intestinal Immune Disorders and Gut Barrier Dysfunctions Based on Microbiome-Metabolomics Analysis
Authors: Zhou Rongrong , He Dan , Xie Jing , Zhou Qingyijun , Zeng Hongliang , Li Hongmei , Huang Luqi 
Published: April 2021

Cyclophosphamide (CTX), used in cancer chemotherapy, a high dose of which would cause immunosuppressive effect and intestinal mucosa damage. American ginseng (Panax quinquefolius L.) has a long history of functional food use for immunological disorder, colitis, cancer, and so on. This study aimed to illustrate the underlying mechanism of American ginseng’s immunomodulatory effect in CTX-induced mice. In this study, all groups of American ginseng (American ginseng polysaccharide [AGP], American ginseng ginsenoside [AGG], co-treated with American ginseng polysaccharide and ginsenoside [AGP_AGG]) have relieve the immune disorder by reversing the lymphocyte subsets ratio in spleen and peripheral blood, as well as stimulating CD4+T cells and IgA-secreting cells in small intestine. These three treatment groups, especially AGP_AGG co-treated group recovered the intestine morphology that up-regulated villus height (VH)/crypt depth (CD) ratio, areas of mucins expression, quantity of goblet cells, and expression of tight junction proteins (ZO-1, occludin). Importantly, the microbiome-metabolomics analysis was applied in this study to illustrate the possible immuno-modulating mechanism. The synergistic effect of polysaccharides and ginsenosides (AGP_AGG group) restored the gut microbiota composition and increased various beneficial mucosa-associated bacterial taxa Clostridiales, Bifidobacterium, and Lachnospiraceae, while decreased harmful bacteria Escherichia-Shigella and Peptococcaceae. Also, AGP_AGG group altered various fecal metabolites such as uric acid, xanthurenic acid, acylcarnitine, 9,10-DHOME, 13-HDoHE, LysoPE15:0, LysoPC 16:0, LysoPI 18:0, and so on, that associated with immunometabolism or protective effect of gut barrier. These results suggest AG, particularly co-treated of polysaccharide and ginsenoside may be used as immunostimulants targeting microbiome-metabolomics axis to prevent CTX-induced side effects in cancer patients.
Thrombotic Events in COVID-19 Are Associated With a Lower Use of Prophylactic Anticoagulation Before Hospitalization and Followed by Decreases in Platelet Reactivity
Authors: Clark Chantal C. , Jukema Bernard N. , Barendrecht Arjan D. , Spanjaard Judith S. , Jorritsma Nikita K. N. , Smits Simone , de Maat Steven , Seinen Cor W. , Verhoef Sandra , Parr Naomi M. J. , Sebastian Silvie A. E. , Koekman Arnold C. , van Wesel Annet C. W. , van Goor Harriet M. R. , Spijkerman Roy , Bongers Suzanne H. , van der Vries Erhard , Nierkens Stefan , Boes Marianne , Koenderman Leo , Kaasjager Karin A. H. , Maas Coen 
Published: April 2021

Background: Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and a high incidence of thrombotic event(s) (TE).Objectives: To study platelet reactivity in hospitalized COVID-19 patients and determine a possible association with the clinical outcomes thrombosis and all-cause mortality.Methods: Seventy nine hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality.Results: The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not develop a TE [median age of 55 vs. 70 years; adjusted odds ratio (AOR) = 0.96 per 1 year of age, 95% confidence interval (CI) 0.92–1.00; p = 0.041]. Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a thrombotic complication than patients that were not (18 vs. 54%; AOR = 0.19, 95% CI 0.04–0.84; p = 0.029). Conversely, having asthma strongly increased the risk on TE development (AOR = 6.2, 95% CI 1.15–33.7; p = 0.034). No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients (n = 79) and COVID-19 negative hospitalized control patients (n = 21), nor between COVID-19 positive survivors or non-survivors. However, patients showed decreased platelet reactivity in response to TRAP-6 following TE development.Conclusion: We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation.
The Incidence of Stroke in Indigenous Populations of Countries With a Very High Human Development Index: A Systematic Review Protocol
Authors: Balabanski Anna H. , Dos Santos Angela , Woods John A. , Thrift Amanda G. , Kleinig Timothy J. , Suchy-Dicey Astrid , Siri Susanna Ragnhild , Boden-Albala Bernadette , Krishnamurthi Rita , Feigin Valery L. , Buchwald Dedra , Ranta Annemarei , Mienna Christina S. , Zavaleta Carol , Churilov Leonid , Burchill Luke , Zion Deborah , Longstreth W. T. , Tirschwell David L. , Anand Sonia , Parsons Mark W. , Brown Alex , Warne Donald K. , Harwood Matire , Katzenellenbogen Judith M. 
Published: April 2021

Background and Aims: Despite known Indigenous health and socioeconomic disadvantage in countries with a Very High Human Development Index, data on the incidence of stroke in these populations are sparse. With oversight from an Indigenous Advisory Board, we will undertake a systematic review of the incidence of stroke in Indigenous populations of developed countries or regions, with comparisons between Indigenous and non-Indigenous populations of the same region, though not between different Indigenous populations.Methods: Using PubMed, OVID-EMBASE, and Global Health databases, we will examine population-based incidence studies of stroke in Indigenous adult populations of developed countries published 1990-current, without language restriction. Non-peer-reviewed sources, studies including &lt;10 Indigenous People, or with insufficient data to determine incidence, will be excluded. Two reviewers will independently validate the search strategies, screen titles and abstracts, and record reasons for rejection. Relevant articles will undergo full-text screening, with standard data extracted for all studies included. Quality assessment will include Sudlow and Warlow's criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and the CONSIDER checklist for Indigenous research.Results: Primary outcomes include crude, age-specific and/or age-standardized incidence of stroke. Secondary outcomes include overall stroke rates, incidence rate ratio and case-fatality. Results will be synthesized in figures and tables, describing data sources, populations, methodology, and findings. Within-population meta-analysis will be performed if, and where, methodologically sound and comparable studies allow this.Conclusion: We will undertake the first systematic review assessing disparities in stroke incidence in Indigenous populations of developed countries. Data outputs will be disseminated to relevant Indigenous stakeholders to inform public health and policy research.
Impact of Intensive Gait Training With and Without Electromechanical Assistance in the Chronic Phase After Stroke–A Multi-Arm Randomized Controlled Trial With a 6 and 12 Months Follow Up
Authors: Palmcrantz Susanne , Wall Anneli , Vreede Katarina Skough , Lindberg Påvel , Danielsson Anna , Sunnerhagen Katharina S. , Häger Charlotte K. , Borg Jörgen 
Published: April 2021

Introduction:Movement related impairments and limitations in walking are common long-term after stroke. This multi-arm randomized controlled trial explored the impact of training with an electromechanically assisted gait training (EAGT) system, i.e., the Hybrid Assistive Limb®(HAL), when integrated with conventional rehabilitation focused on gait and mobility.Material and Methods:Participants, aged 18–70 years with lower extremity paresis but able to walk with manual support or supervision 1–10 years after stroke, were randomized to (A) HAL-training on a treadmill, combined with conventional rehabilitation interventions (HAL-group), or (B) conventional rehabilitation interventions only (Conventional group), 3 days/week for 6 weeks, or (C) no intervention (Control group). Participants in the Control group were interviewed weekly regarding their scheduled training. Primary outcome was endurance in walking quantified by the 6 Minute Walk Test (6MWT). A rater blinded to treatment allocation performed assessments pre- and post-intervention and at follow-ups at 6 and 12 months. Baseline assessment included the National Institute of Health Stroke Scale (NIHSS) and the Modified Ranking Scale (MRS). Secondary outcomes included the Fugl Meyer Assessment- Lower Extremity, 10 Meter Walk Test, Berg Balance Scale (BBS), Barthel Index (BI) and perceived mobility with the Stroke Impact Scale.Results:A total of 48 participants completed the intervention period. The HAL-group walked twice as far as the Conventional group during the intervention. Post-intervention, both groups exhibited improved 6 MWT results, while the Control group had declined. A significant improvement was only found in the Conventional group and when compared to the Control group (Tukey HSDp= 0.022), and not between the HAL group and Conventional group (Tukey HSDp= 0.258) or the HAL- group and the Control group (Tukey HSDp= 0.447). There was also a significant decline in the Conventional group from post-intervention to 6 months follow up (p= 0.043). The best fitting model to predict outcome included initial balance (BBS), followed by stroke severity (NIHSS), and dependence in activity and participation (BI and MRS).Conclusion:Intensive conventional gait training induced significant improvements long-term after stroke while integrating treadmill based EAGT had no additional value in this study sample. The results may support cost effective evidence-based interventions for gait training long-term after stroke and further development of EAGT.Trial registration:Published onclinicaltrials.gov(NCT02545088) August 24, 2015.
Computed-Tomography-Based Radiomics Model for Predicting the Malignant Potential of Gastrointestinal Stromal Tumors Preoperatively: A Multi-Classifier and Multicenter Study
Authors: Wang Minhong , Feng Zhan , Zhou Lixiang , Zhang Liang , Hao Xiaojun , Zhai Jian 
Published: April 2021

Background: Our goal was to establish and verify a radiomics risk grading model for gastrointestinal stromal tumors (GISTs) and to identify the optimal algorithm for risk stratification.Methods: We conducted a retrospective analysis of 324 patients with GISTs, the presence of which was confirmed by surgical pathology. Patients were treated at three different hospitals. A training cohort of 180 patients was collected from the largest center, while an external validation cohort of 144 patients was collected from the other two centers. To extract radiomics features, regions of interest (ROIs) were outlined layer by layer along the edge of the tumor contour on CT images of the arterial and portal venous phases. The dimensionality of radiomic features was reduced, and the top 10 features with importance value above 5 were selected before modeling. The training cohort used three classifiers [logistic regression, support vector machine (SVM), and random forest] to establish three GIST risk stratification prediction models. The receiver operating characteristic curve (ROC) was used to compare model performance, which was validated by external data.Results: In the training cohort, the average area under the curve (AUC) was 0.84 ± 0.07 of the logistic regression, 0.88 ± 0.06 of the random forest, and 0.81 ± 0.08 of the SVM. In the external validation cohort, the AUC was 0.85 of the logistic regression, 0.90 of the random forest, and 0.80 of the SVM. The random forest model performed the best in both the training and the external validation cohorts and could be generalized.Conclusion: Based on CT radiomics, there are multiple machine-learning models that can predict the risk of GISTs. Among them, the random forest algorithm had the highest prediction efficiency and could be readily generalizable. Through external validation data, we assume that the random forest model may be used as an effective tool to guide preoperative clinical decision-making.
Laparoscopic vs. Open Repeat Hepatectomy for Recurrent Liver Tumors: A Propensity Score–Matched Study and Meta-Analysis
Authors: Chen Jia-Feng , Fu Xiu-Tao , Gao Zheng , Shi Ying-Hong , Tang Zheng , Liu Wei-Ren , Zhang Xin , Gao Qiang , Ding Guang-Yu , Song Kang , Wang Xiao-Ying , Zhou Jian , Fan Jia , Ding Zhen-Bin 
Published: April 2021

Background: It remains unclear whether the short-term benefits of laparoscopic repeat hepatectomy (LRH) accrue to patients with recurrent liver tumors. The present study aimed to report our own center's experience and perform a meta-analysis to evaluate the safety and feasibility of LRH in comparison with open repeat hepatectomy (ORH) for treating recurrent liver tumors.Patients and Methods: A propensity score–matched study was performed including 426 patients receiving LRH or ORH for recurrent hepatocellular carcinoma between January 2017 and December 2018. Surgical outcomes and perioperative inflammation-based markers, including monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune–inflammation index were collected from medical records and analyzed. Additionally, a systematic literature review was performed to identify relevant studies in PubMed, EMBASE, Web of Science, and Cochrane library databases up to October 1, 2020. Information including patient demographics, pathologic characteristics, and short-term outcomes was extracted and analyzed using random- or fixed-effects models.Results: Of 68 LRHs, 57 were matched with an ORH finally. Our study demonstrated that LRH was significantly associated with less intraoperative blood loss (50 vs. 100 mL; P &lt; 0.001), lower rate of hepatic inflow occlusion (10.52 vs. 33.3%; P = 0.003), and shorter postoperative hospital stay (5 vs. 6 days; P = 0.001) after 1:1 propensity score matching. The operation time, rate of blood transfusion, and postoperative complications were similar between the two groups. Moreover, all four inflammation-based markers were significantly lower in LRH group on postoperative day 1. In the meta-analysis, a total of 12 studies comprising 1,315 patients receiving repeat hepatectomy met the selection criteria. Similar to our own study, the meta-analysis showed shorter hospital stay [standard mean difference (SMD) = −0.51, 95% confidence interval (CI) = −0.79 to −0.22, P &lt; 0.001], less intraoperative blood loss (SMD = −0.79, 95% CI = −1.11 to −0.47, P &lt; 0.001), and lower rate of major postoperative complications [odds ratio (OR) = 0.35, 95% CI = 0.19–0.66, P = 0.001] in the LRH group. There was no difference in the field of overall postoperative complication and operation time between LRH and ORH groups.Conclusion: Compared with ORH, LRH results in relatively better surgical outcomes and faster postoperative recovery. It could be considered a feasible and effective option for the treatment of recurrent liver tumors.
A Combined Prediction Model for Lymph Node Metastasis Based on a Molecular Panel and Clinicopathological Factors in Oral Squamous Cell Carcinoma
Authors: Wang Shu , Li Tiancheng , Liu Huan , Wei Wei , Yang Yang , Wang Chong , Li Bo , Han Zhengxue , Feng Zhien 
Published: April 2021

ObjectiveLymph node metastasis is the most important factor influencing the prognosis of oral squamous cell carcinoma (OSCC) patients. However, there is no proper method for predicting lymph node metastasis. This study aimed to construct and validate a preoperative prediction model for lymph node metastasis and guide personalized neck management based on the gene expression profile and clinicopathological parameters of OSCC.MethodsBased on a previous study of related genes in OSCC, the mRNA expression of candidate genes was evaluated by real-time PCR in OSCC specimens. In this retrospective study, the gene expression profile and clinicopathological parameters of 112 OSCC patients were combined to construct the best prediction model for lymph node metastasis of OSCC. The model was validated with 95 OSCC samples in this study. Logistic regression analysis was used. The area under the curve (AUC) ultimately determined the diagnostic value of the prediction model.ResultsThe two genes CDKN2A + PLAU were closely related to lymph node metastasis of oral squamous cell carcinoma. The model with the combination of CDKN2A, PLAU, T stage and pathological grade was the best in predicting lymph node metastasis (AUC = 0.807, 95% CI: 0.713-0.881, P=0.0001). The prediction model had a specificity of 96% and sensitivity of 72.73% for stage T1 and T2 OSCC (AUC = 0.855, 95% CI: 0.697-0.949, P=0.0001).ConclusionsHigh expression of CDKN2A and PLAU was associated with lymph node metastasis in OSCC. The prediction model including CDKN2A, PLAU, T stage and pathological grade can be used as the best diagnostic model for lymph node metastasis in OSCC.