bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunologic Biomarkers in Peripheral Blood of Persons With Tuberculosis and Advanced HIV
Authors: Queiroz Artur T. L. , Araújo-Pereira Mariana , Barreto-Duarte Beatriz , Gomes-Silva Adriano , Costa Allyson G. , Andrade Alice M. S. , Miguez-Pinto João Pedro , Spener-Gomes Renata , Souza Alexandra B. , Benjamin Aline , Sant’Anna Flavia , Figueiredo Marina C. , Mave Vidya , Salgame Padmini , Ellner Jerrold J. , Sterling Timothy R. , Cordeiro-dos-Santos Marcelo , Andrade Bruno B. , Rolla Valeria C. 
Published: June 2022

IntroductionTuberculosis (TB) is a common opportunistic infection among people living with HIV. Diagnostic tests such as culture, Xpert-MTB-RIF, and ULTRA have low sensitivity in paucibacillary TB disease; a blood biomarker could improve TB diagnostic capabilities. We assessed soluble factors to identify biomarkers associated with TB among persons with advanced HIV.MethodsA case-control (1:1) study was conducted, with participants from Rio de Janeiro and Manaus, Brazil. People living with HIV presenting with CD4 count ≤100 cells/mm3 were eligible to participate. Cases had culture-confirmed TB (N=15) (positive for Mycobacterium tuberculosis [Mtb]); controls had HIV-infection only (N=15). Study visits included baseline, month 2 and end of TB therapy, during which samples of peripheral blood were obtained. A panel containing 29 biomarkers including cytokines, chemokines and growth factors was utilized to assess candidate biomarkers using Luminex technology in cryopreserved EDTA plasma samples. We used neural network analysis, based on machine learning, to identify biomarkers (single or in combination) that best distinguished cases from controls. Additional multi-dimensional analyses provided detailed profiling of the systemic inflammatory environment in cases and controls.ResultsMedian CD4 count and HIV-1 RNA load values were similar between groups at all timepoints. Persons with TB had lower body mass index (BMI) (median=19.6, Interquartile Range [IQR]=18.6-22.3) than controls (23.7; IQR: 21.8 = 25.5, p=0.004). TB coinfection was also associated with increased frequency of other comorbidities. The overall profile of plasma cytokines, chemokines and growth factors were distinct between the study groups at all timepoints. Plasma concentrations of IL-15 and IL-10 were on average lower in TB cases than in controls. When used in combination, such markers were able to discriminate between TB cases and controls with the highest degree of accuracy at each study timepoint.ConclusionAmong persons with advanced HIV, plasma concentrations of IL-15 and IL-10 can be used in combination to identify TB disease regardless of time on anti-TB treatment.
Changes Within H3K4me3-Marked Histone Reveal Molecular Background of Neutrophil Functional Plasticity
Authors: Piatek Paweł , Namiecinska Magdalena , Lewkowicz Natalia , Kulińska-Michalska Małgorzata , Jabłonowski Zbigniew , Matysiak Mariola , Dulska Justyna , Michlewska Sylwia , Wieczorek Marek , Lewkowicz Przemysław 
Published: June 2022

Neutrophils are a heterogenous population capable of both antimicrobial functions and suppressor ones, however, no specific pattern of transcription factors controlling this plasticity has been identified. We observed rapid changes in the neutrophil status after stimulation with LPS, pre-activating concentration of TNF-α, or IL-10. Chromatin immunoprecipitation sequencing (ChIP-Seq) analysis of histone H3K4me3 allowed us to identify various transcriptional start sites (TSSs) associated with plasticity and heterogeneity of human neutrophils. Gene Ontology analysis demonstrated great variation within target genes responsible for neutrophil activation, cytokine production, apoptosis, histone remodelling as well as NF-κB transcription factor pathways. These data allowed us to assign specific target genes positioned by H3K4me3-marked histone with a different pattern of gene expression related to NF-κB pathways, apoptosis, and a specific profile of cytokines/chemokines/growth factors realised by neutrophils stimulated by LPS, IL-10, or TNF-α. We discovered IL-10-induced apoptotic neutrophils being transcriptionally active cells capable of switching the profile of cytokines/chemokines/growth factors desired in resolving inflammation via non-canonical NF-κB pathway with simultaneous inhibition of canonical NF-κB pathway. As apoptotic/suppressive neutrophils induced by IL-10 via positioning genes within H3K4me3-marked histone were transcriptionally active, newly described DNA binding sites can be considered as potential targets for immunotherapy.Graphical AbstractH3K4me3 histone ChIP-Seq analysis reveals molecular drivers critical for switching neutrophils from their pro- to anti-inflammatory properties.
Melting Antarctic Sea Ice Is Yielding Adverse Effects on a Short-Lived Squid Species in the Antarctic Adjacent Waters
Authors: Liu Hewei , Yu Wei , Chen Xinjun 
Published: June 2022

Variation in Antarctic sea ice strongly impacts marine ecosystem and fisheries. In this study, Antarctic sea ice extent (SIE) was used as an indicator to characterize the Antarctic sea ice variation, and its impact on habitat pattern of Argentine shortfin squid Illex argentinus, a climate-sensitive squid species extensively distributed in the Antarctic adjacent waters, was assessed using the habitat suitability index (HSI) modeling approach. The HSI model was established on the basis of the fisheries data and sea water temperature at critical depths of 50, 100, and 200 m in the high-sea fishing ground of the Southwest Atlantic Ocean from January to April during 1979–2017. Results showed that a significantly positive correlation was found between SIE and the areas of suitable habitat of I. argentinus. The years with high and low SIE were selected and divided into two groups from 1979 to 2017. Generally, the year group with high SIE yielded warmer sea water temperature at different depths; consequently, the suitable habitats enlarged; and the optimal temperature isotherm for I. argentinus moved northward, resulting in a northward movement of suitable habitats. On the contrary, the situation in the year group with low SIE was opposite. Our findings suggest that the melting Antarctic sea ice is yielding adverse effects on I. argentinus habitat in the Southwest Atlantic Ocean by affecting the sea water temperature at three critical depths.
Development and Implementation of the AIDA International Registry for Patients With Undifferentiated Systemic AutoInflammatory Diseases
Authors: Della Casa Francesca , Vitale Antonio , Lopalco Giuseppe , Ruscitti Piero , Ciccia Francesco , Emmi Giacomo , Cattalini Marco , Wiesik-Szewczyk Ewa , Maggio Maria Cristina , Ogunjimi Benson , Sfikakis Petros P. , Tufan Abdurrahman , Al-Mayouf Sulaiman M. , Del Giudice Emanuela , Aragona Emma , La Torre Francesco , Sota Jurgen , Colella Sergio , Di Cola Ilenia , Iacono Daniela , Mattioli Irene , Jahnz-Rózyk Karina , Joos Rik , Laskari Katerina , Gaggiano Carla , Abbruzzese Anna , Cipriani Paola , Rozza Gelsomina , AlSaleem Alhanouf , Yildirim Derya , Tarsia Maria , Ragab Gaafar , Ricci Francesca , Cardinale Fabio , Korzeniowska Marcelina , Frassi Micol , Caggiano Valeria , Saad Moustafa Ali , Pereira Rosa Maria , Berlengiero Virginia , Gentileschi Stefano , Guerriero Silvana , Giani Teresa , Gelardi Viviana , Iannone Florenzo , Giardini Henrique Ayres Mayrink , Almaghlouth Ibrahim A. , Kardas Riza Can , Ait-Idir Djouher , Frediani Bruno , Balistreri Alberto , Fabiani Claudia , Rigante Donato , Cantarini Luca 
Published: June 2022

ObjectiveThis paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs).MethodsThis is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research. The instrument is endowed with flexibility, and it could change over time according to the scientific acquisitions and potentially communicate with other similar tools; this platform ensures security, data quality and data governance.ResultsThe focus of the AIDA project is connecting physicians and researchers from all over the world to shed a new light on heterogeneous rare diseases. Since its birth, 110 centers from 23 countries and 4 continents have joined the AIDA project. Fifty-four centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 179 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry is collecting baseline and follow-up data using 3,769 fields organized into 23 instruments, which include demographics, history, symptoms, trigger/risk factors, therapies, and healthcare information access for USAIDs patients.ConclusionsThe development of the AIDA International Registry for USAIDs patients will facilitate the online collection of real standardized data, connecting a worldwide group of researchers: the Registry constitutes an international multicentre observational groundwork aimed at increasing the patient cohort of USAIDs in order to improve our knowledge of this peculiar cluster of autoinflammatory diseases. NCT 05200715 available at https://clinicaltrials.gov/.
An Intelligent Diagnostic System for Thyroid-Associated Ophthalmopathy Based on Facial Images
Authors: Huang Xiao , Ju Lie , Li Jian , He Linfeng , Tong Fei , Liu Siyu , Li Pan , Zhang Yun , Wang Xin , Yang Zhiwen , Xiong Jianhao , Wang Lin , Zhao Xin , He Wanji , Huang Yelin , Ge Zongyuan , Yao Xuan , Yang Weihua , Wei Ruili 
Published: June 2022

BackgroundThyroid-associated ophthalmopathy (TAO) is one of the most common orbital diseases that seriously threatens visual function and significantly affects patients’ appearances, rendering them unable to work. This study established an intelligent diagnostic system for TAO based on facial images.MethodsPatient images and data were obtained from medical records of patients with TAO who visited Shanghai Changzheng Hospital from 2013 to 2018. Eyelid retraction, ocular dyskinesia, conjunctival congestion, and other signs were noted on the images. Patients were classified according to the types, stages, and grades of TAO based on the diagnostic criteria. The diagnostic system consisted of multiple task-specific models.ResultsThe intelligent diagnostic system accurately diagnosed TAO in three stages. The built-in models pre-processed the facial images and diagnosed multiple TAO signs, with average areas under the receiver operating characteristic curves exceeding 0.85 (F1 score &gt;0.80).ConclusionThe intelligent diagnostic system introduced in this study accurately identified several common signs of TAO.
Associations of Sleep Disorders With Depressive Symptoms in Early and Prodromal Parkinson’s Disease
Authors: Ma Jiangnan , Dou Kaixin , Liu Ruize , Liao Yajin , Yuan Zengqiang , Xie Anmu 
Published: June 2022

BackgroundNon-motor symptoms, including sleep disorders and depression, are common in Parkinson’s disease (PD). The purpose of our study is to explore the effect of sleep disorders, including the probable rapid eye movement (REM) sleep behavior disorder (pRBD) and the daytime sleepiness, on depressive symptoms in patients with early and prodromal PD.MethodsA total of 683 participants who obtained from the Parkinson Progression Markers Initiative (PPMI) were included, consisting of 423 individuals with early PD, 64 individuals with prodromal PD, and 196 healthy controls (HCs), who were followed up to 5 years from baseline. Multiple linear regression models and linear mixed-effects models were conducted to explore the relationship between sleep disorders and depression at baseline and longitudinally, respectively. Multiple linear regression models were used to further investigate the association between the change rates of daytime sleepiness score and depression-related score. Mediation analyses were also performed.ResultsAt baseline analysis, individuals with early and prodromal PD, who had higher RBD screening questionnaire (RBDSQ) score, or who were considered as pRBD, or who manifested specific behaviors of RBD (things falling down when sleep or disturbance of sleep), showed significantly the higher score of depression-related questionnaires. Our 5-year follow-up study showed that sleep disorders, including pRBD and daytime sleepiness, were associated with the increased depressive-related score in individuals with early and prodromal PD. Interestingly, we also found that the increased possibilities of daytime sleepiness were associated with depressive-related score. Finally, mediation analysis demonstrated that the relationship between RBD and depressive symptoms was partially mediated by autonomic symptoms, such as postural hypertension, salivation, dysphagia, and constipation.ConclusionOur study shows that sleep disorders, including pRBD and daytime sleepiness, are associated with depression at baseline and longitudinally, which is partially mediated by the autonomic dysfunction in early and prodromal PD, with an implication that sleep management is of great value for disease surveillance.
SAA1 Expression as a Potential Prognostic Marker of the Tumor Microenvironment in Glioblastoma
Authors: Cao Kangxi , Jiang Xingyu , Wang Baishun , Ni Zhaohui , Chen Yan 
Published: June 2022

BackgroundGlioblastoma (GBM) is the most common primary brain malignant tumor, and patients with GBM have a poor prognosis. The tumor microenvironment (TME) is connected to tumorigenesis and prognosis. However, the TME-related genes and therapeutic targets in GBM are yet to be identified. Thus, the presented study aimed to identify TME-related biomarkers in GBM and develop a novel target for the treatment of the disease.MethodsESTIMATE computational methods were utilized to estimate the amounts of stromal and immune components in 697 patients with glioma from the Cancer Genome Atlas database. Then, the protein–protein interaction network and univariate Cox regression analyzed the differentially expressed genes. Serum amyloid A1 (SAA1) was determined to be a predictive factor. SAA1 expression was statistically significant in GBM compared to the normal samples and other glioma subtypes and negatively associated with survival. Independent prognostic analysis identified SAA1 as a TME-related prognostic factor. Furthermore, Western blot analysis showed that SAA1 is upregulated in GBM, which was confirmed by the external validation in the Chinese Glioma Genome Atlas. The gene set enrichment analysis in GBM revealed enrichment of immune-related activities in the SAA1 high-expression group, while mitosis and cell cycle were enriched in the low-expression group. CIBERSORT analysis of the tumor-infiltrating immune cell proportion revealed that M2 macrophages, neutrophils, activated mast cells, resting mast cells, and regulatory T cells were correlated with SAA1 expression. Finally, immune checkpoint genes, tumor mutation burden, and drug sensitivity were also analyzed between the high- and low-expression groups.ConclusionSAA1 could be a distinctive gene between GBM and other subtype gliomas, and thus a novel biomarker for estimating the survival and TME status. The altered expression level shifts the primary function of SAA1 from cell cycle and mitosis to immune activity. High expression of SAA1 is associated with poor survival and upregulates the expression of LAIR1 and TNFSF14, thereby deeming it as the drug sensitivity indicator for XAV939, TGX-221, and lapatinib in GBM immune therapy.
A Radiomics Nomogram for Classifying Hematoma Entities in Acute Spontaneous Intracerebral Hemorrhage on Non-contrast-Enhanced Computed Tomography
Authors: Wang Jia , Xiong Xing , Ye Jing , Yang Yang , He Jie , Liu Juan , Yin Yi-Li 
Published: June 2022

AimTo develop and validate a radiomics nomogram on non-contrast-enhanced computed tomography (NECT) for classifying hematoma entities in patients with acute spontaneous intracerebral hemorrhage (ICH).Materials and MethodsOne hundred and thirty-five patients with acute intraparenchymal hematomas and baseline NECT scans were retrospectively analyzed, i.e., 52 patients with vascular malformation-related hemorrhage (VMH) and 83 patients with primary intracerebral hemorrhage (PICH). The patients were divided into training and validation cohorts in a 7:3 ratio with a random seed. After extracting the radiomics features of hematomas from baseline NECT, the least absolute shrinkage and selection operator (LASSO) regression was applied to select features and construct the radiomics signature. Multivariate logistic regression analysis was used to determine the independent clinical-radiological risk factors, and a clinical model was constructed. A predictive radiomics nomogram was generated by incorporating radiomics signature and clinical-radiological risk factors. Nomogram performance was assessed in the training cohort and tested in the validation cohort. The capability of models was compared by calibration, discrimination, and clinical benefit.ResultsSix features were selected to establish radiomics signature via LASSO regression. The clinical model was constructed with the combination of age [odds ratio (OR): 6.731; 95% confidence interval (CI): 2.209–20.508] and hemorrhage location (OR: 0.089; 95% CI: 0.028–0.281). Radiomics nomogram [area under the curve (AUC), 0.912 and 0.919] that incorporated age, location, and radiomics signature outperformed the clinical model (AUC, 0.816 and 0.779) and signature (AUC, 0.857 and 0.810) in the training cohort and validation cohorts, respectively. Good calibration and clinical benefit of nomogram were achieved in the training and validation cohorts.ConclusionNon-contrast-enhanced computed tomography-based radiomics nomogram can predict the individualized risk of VMH in patients with acute ICH.
Opportunities and Limitations of a Gaze-Contingent Display to Simulate Visual Field Loss in Driving Simulator Studies
Authors: Biebl Bianca , Arcidiacono Elena , Kacianka Severin , Rieger Jochem W. , Bengler Klaus 
Published: June 2022

BackgroundResearch on task performance under visual field loss is often limited due to small and heterogenous samples. Simulations of visual impairments hold the potential to account for many of those challenges. Digitally altered pictures, glasses, and contact lenses with partial occlusions have been used in the past. One of the most promising methods is the use of a gaze-contingent display that occludes parts of the visual field according to the current gaze position. In this study, the gaze-contingent paradigm was implemented in a static driving simulator to simulate visual field loss and to evaluate parallels in the resulting driving and gaze behavior in comparison to patients.MethodsThe sample comprised 15 participants without visual impairment. All the subjects performed three drives: with full vision, simulated left-sided homonymous hemianopia, and simulated right-sided homonymous hemianopia, respectively. During each drive, the participants drove through an urban environment where they had to maneuver through intersections by crossing straight ahead, turning left, and turning right.ResultsThe subjects reported reduced safety and increased workload levels during simulated visual field loss, which was reflected in reduced lane position stability and greater absence of large gaze movements. Initial compensatory strategies could be found concerning a dislocated gaze position and a distorted fixation ratio toward the blind side, which was more pronounced for right-sided visual field loss. During left-sided visual field loss, the participants showed a smaller horizontal range of gaze positions, longer fixation durations, and smaller saccadic amplitudes compared to right-sided homonymous hemianopia and, more distinctively, compared to normal vision.ConclusionThe results largely mirror reports from driving and visual search tasks under simulated and pathological homonymous hemianopia concerning driving and scanning challenges, initially adopted compensatory strategies, and driving safety. This supports the notion that gaze-contingent displays can be a useful addendum to driving simulator research with visual impairments if the results are interpreted considering methodological limitations and inherent differences to the pathological impairment.
Long-Term Azithromycin Treatment in Pediatric Primary Ciliary Dyskinesia: A Retrospective Study
Authors: Guan Yuhong , Zhang Xiang , Yang Haiming , Xu Hui , Zhao Shunying 
Published: June 2022

ObjectivesPrimary ciliary dyskinesia (PCD) is a rare genetic disease mainly involved in lung dysfunction. PCD patient outcomes after azithromycin (AZM) treatment have rarely been reported. This study was aimed to assess AZM treatment effects on disease progression of pediatric PCD patients.Study DesignThis retrospective follow-up study involved PCD patients diagnosed from 2009 to 2021. Changes of clinical outcomes, pulmonary function, and chest computed tomography findings were compared between untreated and AZM-treated patients.ResultsOf 71 enrolled patients (median follow-up duration of 3.1 years), 34 received AZM (AZM-treated group) and 37 received no AZM (AZM-untreated group). At diagnosis, no significant intergroup differences in age, sex, height, weight, number of respiratory exacerbations, and FEV1% and FVC% predicted values were found, although FEF25–75% predicted was lower in AZM-treated group. Between treatment initiation and follow-up, patients in AZM-treated group had less respiratory exacerbations than that of AZM-untreated group (mean ± SD, 1.4 ± 0.8 vs. 3.0 ± 2.1, times/year P = 0.001) and fewer AZM-treated group patients exhibited exercise intolerance. Increases above baseline of AZM-treated FEV1% and FVC% predicted values exceeded that of AZM-untreated group, but intergroup differences were insignificant (FEV1% predicted: (median, IQR) 5.3 [−13.4, 9.4] vs. 1.8 [−12.1, 9.5], P = 0.477; FVC% predicted: (median, IQR) 6.7 [−7.6, 18.8] vs. 1.6 [−5.6, 7.6], P = 0.328).ConclusionLong-term AZM treatment can reduce respiratory infection frequency and may maintain pulmonary diseases stable in pediatric PCD patients with worse lung function.
Body Structural Description Impairment in Complex Regional Pain Syndrome Type I
Authors: Biran Iftah , Book Andrea , Aviram Liron , Bregman Noa , Bahagali Einat , Tripto Assaf 
Published: June 2022

BackgroundComplex Regional Pain Syndrome (CRPS) is a clinical syndrome composed of chronic pain, motor impairment, and autonomic dysfunction, usually affecting a limb. Although CRPS seems to be a peripheral disorder, it is accompanied by parietal alterations leading to body schema impairments (the online representations of the body). Impairments to body structural description (the topographical bodily map) were not assessed systematically in CRPS. A patient we encountered with severe disruption to her bodily structural description led us to study this domain further.AimsTo document aberrant body structural description in subjects with CRPS using an object assembly task.MethodsBody Schema Study: 6 subjects with CRPS-I and six age and sex-matched healthy controls completed visual puzzles taken from WAIS-III and WAIS-R. The puzzles were either related to the human body or non-human body objects. Mann–Whitney U-tests were performed to compare groups’ performances.ResultsThe CRPS group received relatively lower scores compared to controls for human body objects (u = 3, p &lt; 0.05), whereas the non-human object scoring did not reveal significant differences between groups (u = 9, p &gt; 0.05).ConclusionCRPS subjects suffer from impaired body structural description, taking the form of body parts disassembly and body parts discontinuity. This impairment can serve as a nidus for aberrant psychological representation of the body.