bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dengue induces iNOS expression and nitric oxide synthesis in platelets through IL-1R
Authors: Pinheiro Mariana Brandi Mendonça , Rozini Stephane Vicente , Quirino-Teixeira Anna Cecíllia , Barbosa-Lima Giselle , Lopes Juliana F. , Sacramento Carolina Q. , Bozza Fernando A. , Bozza Patrícia T. , Hottz Eugenio D. 
Published: December 2022

IntroductionDengue is an arthropod-born disease caused by dengue virus (DENV), that may manifest as a mild illness or severe form, characterized by hemorrhagic fever and shock. Nitric oxide (NO) is a vasodilator signaling molecule and an inhibitor of platelet aggregation known to be increased in platelets from dengue patients. However, the mechanisms underlying NO synthesis by platelets during dengue are not yet elucidated. IL-1β is a pro-inflammatory cytokine able to induce iNOS expression in leukocytes and present in dengue patients at high levels. Nevertheless, the role of IL-1β in platelet activation, especially regarding iNOS expression, are not clear.MethodsWe prospectively followed a cohort of 28 dengue-infected patients to study NO synthesis in platelets and its relationship with disease outcomes. We used in vitro infection and stimulation models to gain insights on the mechanisms.Results and DiscussionWe confirmed that platelets from dengue patients express iNOS and produce higher levels of NO during the acute phase compared to healthy volunteers, returning to normal levels after recovery. Platelet NO production during acute dengue infection was associated with the presence of warning signs, hypoalbuminemia and hemorrhagic manifestations, suggesting a role in dengue pathophysiology. By investigating the mechanisms, we evidenced increased iNOS expression in platelets stimulated with dengue patients´ plasma, indicating induction by circulating inflammatory mediators. We then investigated possible factors able to induce platelet iNOS expression and observed higher levels of IL-1β in plasma from patients with dengue, which were correlated with NO production by platelets. Since platelets can synthesize and respond to IL-1β, we investigated whether IL-1β induces iNOS expression and NO synthesis in platelets. We observed that recombinant human IL-1β enhanced iNOS expression and dose-dependently increased NO synthesis by platelets. Finally, platelet infection with DENV in vitro induced iNOS expression and NO production, besides the secretion of both IL-1α and IL-1β. Importantly, treatment with IL-1 receptor antagonist or a combination of anti-IL-1α and anti-IL-1β antibodies prevented DENV-induced iNOS expression and NO synthesis. Our data show that DENV induces iNOS expression and NO production in platelets through mechanisms depending on IL-1 receptor signaling.
Circulatory levels of alarmins in patients with non-segmental vitiligo: Potential biomarkers for disease diagnosis and activity/severity assessment
Authors: He Kaiqiao , Wu Wei , Wang Xinju , Dai Wei , Wang Sijia , Li Chunying , Li Shuli 
Published: December 2022

BackgroundNon-segmental vitiligo (NSV) is an autoimmune skin disorder that is difficult to determine disease activity/severity and thus to treat. Alarmins have emerged as promising biomarkers in various diseases, so further confirmation of their potential roles in NSV would be of considerable value. With the present work, we aimed to determine the serum levels of alarmins in patients with NSV, correlate these alarmins with disease activity and severity, and analyze the predictive value of the combination of these markers.Methods104 NSV patients and 56 healthy controls were enrolled at the Xijing Hospital of Fourth Military Medical University between September 1, 2018, and June 30, 2019. The serum levels of alarmins (including IL-33, IL-1α, S100A9, S100A12, S100B, and HMGB1) were measured with enzyme-linked immunosorbent assays. The predictive performance of these biomarkers was evaluated with the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and other representative statistics.ResultsA total of 104 patients with NSV (mean [SD] age, 34.2 [13.0] years; 62 [59.6%] male) and 56 healthy controls (mean [SD] age, 34.8 [13.5] years; 34 [60.7%] male) were enrolled. For vitiligo diagnosis, S100B had the highest sensitivity (92.31%), whereas HMGB1 had the highest specificity (85.71%); the combination of IL-1α, S100B, S100A9, and HMGB1 increased the AUC value to 0.925, with a sensitivity of 87.50% and a specificity of 85.71%. Multivariate logistic regression analysis showed S100B (OR, 1.019; 95% CI, 1.002-1.038; P =0.03), S100A9 (OR, 1.002; 95% CI, 1.001-1.003; P&lt;0.001), and HMGB1 (OR, 1.915; 95% CI, 1.186-3.091; P =0.008) were significantly associated with vitiligo activity. S100A9 had the highest accuracy in discriminating patients at the active stage from the stable stage, with an AUC value of 0.827. The combination of these alarmins had an AUC value of 0.860 to assess disease activity, with a sensitivity of 90.00% and a specificity of 72.97%. Furthermore, S100B (r=0.61, P &lt;0.001), S100A9 (r=0.33, P &lt;0.001), and HMGB1 (r = 0.51, P &lt;0.001) levels were positively correlated with the affected body surface area (BSA) in NSV patients.ConclusionsSerum S100B, S100A9, and HMGB1 might be biomarkers for diagnosing and assessing the activity/severity of NSV, either used alone or in combination.
Inequalities in glycemic and multifactorial cardiovascular control of type 2 diabetes: The Heart Healthy Hoods study
Authors: Ares-Blanco Sara , Polentinos-Castro Elena , Rodríguez-Cabrera Francisco , Gullón Pedro , Franco Manuel , del Cura-González Isabel 
Published: December 2022

AimThis study aimed to analyze glycemic control and multifactorial cardiovascular control targets in people with type 2 diabetes (T2DM) in primary care according to sex and socioeconomic status (SES).Materials and methodsThis is an observational, cross-sectional, and multicenter study. We analyzed all the patients with T2DMM aged between 40 and 75 years in Madrid city (113,265) through electronic health records from 01 August 2017 to 31 July 2018. SES was defined by an area-level socioeconomic index stratified by quintiles (1st quintile: more affluent).OutcomesOutcomes included glycemic control (HbA1c ≤ 7%), 3-factor cardiovascular control [HbA1c ≤ 7%, blood pressure (BP), &lt; 140/90 mmHg, LDL &lt; 100 mg/ml] and 4-factor control [HbA1c ≤ 7%, blood pressure (BP) &lt; 140/90 mmHg, LDL &lt; 100 mg/ml, and BMI &lt; 30 kg/m2]. Multilevel logistic regression models analyzed factors associated with suboptimal glycemic control.ResultsIn total 43.2% were women. Glycemic control was achieved by 63% of patients (women: 64.2% vs. men: 62.4%). Being more deprived was associated with suboptimal glycemic control (OR: 1.20, 95% CI: 1.10–1.32); however, sex was not related (OR: 0.97, 95% CI: 0.94–1.01). The optimal 3-factor control target was reached by 10.3% of patients (women: 9.3% vs. men: 11.2%), especially those in the 5th quintile of SES. The 4-factor control was achieved by 6.6% of the sample. In the 3-factor control target, being women was related to the suboptimal 3-factor control target (OR: 1.26, 95% CI: 1.19– 1.34) but only belonging to SES 4th quintile was related to the unachieved target (OR: 1.47, 95% CI: 1.04–2.07).ConclusionSuboptimal glycemic control was associated with being less affluent and suboptimal 3-factor control target was associated with being women.
Effects of nonsocial and circumscribed interest images on neural mechanisms of emotion regulation in autistic adults
Authors: Antezana Ligia , Coffman Marika C. , DiCriscio Antoinette Sabatino , Richey John A. 
Published: December 2022

IntroductionEmotion dysregulation is commonly reported among autistic individuals. Prior work investigating the neurofunctional mechanisms of emotion regulation (ER) in autistic adults has illustrated alterations in dorsolateral prefrontal cortex (dlPFC) activity, as well as concurrent atypical patterns of activation in subcortical regions related to affect during cognitive reappraisal of social images. Whereas most research examining ER in autism has focused on regulation of negative emotions, the effects of regulating positive emotions has been generally understudied. This is surprising given the relevance of positive motivational states to understanding circumscribed interests (CI) in autism.MethodsAccordingly, the purpose of this study was to use fMRI with simultaneous eye-tracking and pupillometry to investigate the neural mechanisms of ER during passive viewing and cognitive reappraisal of a standardized set of nonsocial images and personalized (self-selected) CI images.ResultsThe autistic group demonstrated comparatively reduced modulation of posterior cingulate cortex (PCC) activation during cognitive reappraisal of CI images compared to viewing of CI, although no eye-tracking/pupillometry differences emerged between-groups. Further, the autistic group demonstrated increased PCC connectivity with left lateral occipital and right supramarginal areas when engaging in cognitive reappraisal vs. viewing CI.DiscussionIn autistic adults, CI may be differentially modulated via PCC. Considering the documented role of the PCC as a core hub of the default mode network, we further postulate that ER of CI could potentially be related to self-referential cognition.
Automatic detection of abnormal hand gestures in patients with radial, ulnar, or median nerve injury using hand pose estimation
Authors: Gu Fanbin , Fan Jingyuan , Cai Chengfeng , Wang Zhaoyang , Liu Xiaolin , Yang Jiantao , Zhu Qingtang 
Published: December 2022

BackgroundRadial, ulnar, or median nerve injuries are common peripheral nerve injuries. They usually present specific abnormal signs on the hands as evidence for hand surgeons to diagnose. However, without specialized knowledge, it is difficult for primary healthcare providers to recognize the clinical meaning and the potential nerve injuries through the abnormalities, often leading to misdiagnosis. Developing technologies for automatically detecting abnormal hand gestures would assist general medical service practitioners with an early diagnosis and treatment.MethodsBased on expert experience, we selected three hand gestures with predetermined features and rules as three independent binary classification tasks for abnormal gesture detection. Images from patients with unilateral radial, ulnar, or median nerve injuries and healthy volunteers were obtained using a smartphone. The landmark coordinates were extracted using Google MediaPipe Hands to calculate the features. The receiver operating characteristic curve was employed for feature selection. We compared the performance of rule-based models with logistic regression, support vector machine and of random forest machine learning models by evaluating the accuracy, sensitivity, and specificity.ResultsThe study included 1,344 images, twenty-two patients, and thirty-four volunteers. In rule-based models, eight features were finally selected. The accuracy, sensitivity, and specificity were (1) 98.2, 91.7, and 99.0% for radial nerve injury detection; (2) 97.3, 83.3, and 99.0% for ulnar nerve injury detection; and (3) 96.4, 87.5, and 97.1% for median nerve injury detection, respectively. All machine learning models had accuracy above 95% and sensitivity ranging from 37.5 to 100%.ConclusionOur study provides a helpful tool for detecting abnormal gestures in radial, ulnar, or median nerve injuries with satisfying accuracy, sensitivity, and specificity. It confirms that hand pose estimation could automatically analyze and detect the abnormalities from images of these patients. It has the potential to be a simple and convenient screening method for primary healthcare and telemedicine application.
Task-based functional MRI challenges in clinical neuroscience: Choice of the best head motion correction approach in multiple sclerosis
Authors: Soares Júlia F. , Abreu Rodolfo , Lima Ana Cláudia , Sousa Lívia , Batista Sónia , Castelo-Branco Miguel , Duarte João Valente 
Published: December 2022

IntroductionFunctional MRI (fMRI) is commonly used for understanding brain organization and connectivity abnormalities in neurological conditions, and in particular in multiple sclerosis (MS). However, head motion degrades fMRI data quality and influences all image-derived metrics. Persistent controversies regarding the best correction strategy motivates a systematic comparison, including methods such as scrubbing and volume interpolation, to find optimal correction models, particularly in studies with clinical populations prone to characterize by high motion. Moreover, strategies for correction of motion effects gain more relevance in task-based designs, which are less explored compared to resting-state, have usually lower sample sizes, and may have a crucial role in describing the functioning of the brain and highlighting specific connectivity changes.MethodsWe acquired fMRI data from 17 early MS patients and 14 matched healthy controls (HC) during performance of a visual task, characterized motion in both groups, and quantitatively compared the most used and easy to implement methods for correction of motion effects. We compared task-activation metrics obtained from: (i) models containing 6 or 24 motion parameters (MPs) as nuisance regressors; (ii) models containing nuisance regressors for 6 or 24 MPs and motion outliers (scrubbing) detected with Framewise Displacement or Derivative or root mean square VARiance over voxelS; and (iii) models with 6 or 24 MPs and motion outliers corrected through volume interpolation. To our knowledge, volume interpolation has not been systematically compared with scrubbing, nor investigated in task fMRI clinical studies in MS.ResultsNo differences in motion were found between groups, suggesting that recently diagnosed MS patients may not present problematic motion. In general, models with 6 MPs perform better than models with 24 MPs, suggesting the 6 MPs as the best trade-off between correction of motion effects and preservation of valuable information. Parsimonious models with 6 MPs and volume interpolation were the best combination for correcting motion in both groups, surpassing the scrubbing methods. A joint analysis regardless of the group further highlighted the value of volume interpolation.DiscussionVolume interpolation of motion outliers is an easy to implement technique, which may be an alternative to other methods and may improve the accuracy of fMRI analyses, crucially in clinical studies in MS and other neurological populations.
Interaural speech asymmetry predicts bilateral speech intelligibility but not listening effort in adults with bilateral cochlear implants
Authors: Burg Emily A. , Thakkar Tanvi D. , Litovsky Ruth Y. 
Published: December 2022

IntroductionBilateral cochlear implants (BiCIs) can facilitate improved speech intelligibility in noise and sound localization abilities compared to a unilateral implant in individuals with bilateral severe to profound hearing loss. Still, many individuals with BiCIs do not benefit from binaural hearing to the same extent that normal hearing (NH) listeners do. For example, binaural redundancy, a speech intelligibility benefit derived from having access to duplicate copies of a signal, is highly variable among BiCI users. Additionally, patients with hearing loss commonly report elevated listening effort compared to NH listeners. There is some evidence to suggest that BiCIs may reduce listening effort compared to a unilateral CI, but the limited existing literature has not shown this consistently. Critically, no studies to date have investigated this question using pupillometry to quantify listening effort, where large pupil sizes indicate high effort and small pupil sizes indicate low effort. Thus, the present study aimed to build on existing literature by investigating the potential benefits of BiCIs for both speech intelligibility and listening effort.MethodsTwelve BiCI adults were tested in three listening conditions: Better Ear, Poorer Ear, and Bilateral. Stimuli were IEEE sentences presented from a loudspeaker at 0° azimuth in quiet. Participants were asked to repeat back the sentences, and responses were scored by an experimenter while changes in pupil dilation were measured.ResultsOn average, participants demonstrated similar speech intelligibility in the Better Ear and Bilateral conditions, and significantly worse speech intelligibility in the Poorer Ear condition. Despite similar speech intelligibility in the Better Ear and Bilateral conditions, pupil dilation was significantly larger in the Bilateral condition.DiscussionThese results suggest that the BiCI users tested in this study did not demonstrate binaural redundancy in quiet. The large interaural speech asymmetries demonstrated by participants may have precluded them from obtaining binaural redundancy, as shown by the inverse relationship between the two variables. Further, participants did not obtain a release from effort when listening with two ears versus their better ear only. Instead, results indicate that bilateral listening elicited increased effort compared to better ear listening, which may be due to poor integration of asymmetric inputs.
Characteristic cerebral perfusion pattern in neuronal intranuclear inclusion disease
Authors: Tai Hong-Fei , Hua Tian-Tian , Zhang Zai-Qiang , Duan Yun-Yun , Zhuo Zhi-Zheng , Wang An , Zhou Yi , Liu Shao-Cheng , Lv Shan 
Published: December 2022

BackgroundNeuronal intranuclear inclusion disease (NIID), which pathogenesis remains largely unclear, is a neurodegenerative disease caused by GGC repeat expansion in NOTCH2NLC gene. As case studies have reported dynamic cortical perfusion changes in NIID, this study aimed to explore the cerebral perfusion pattern in NIID patients.Materials and methodsA total of 38 NIID patients and 34 healthy controls (HCs) were recruited, and 2 NIID patients who had had episodic symptoms within 2 months were excluded. Data on demographic characteristics and clinical features were collected. All participants underwent three-dimensional pseudo-continuous arterial spin labeling perfusion magnetic resonance imaging (MRI) scanning. Voxel-based comparisons of cerebral blood flow (CBF) were conducted.ResultsNIID patients showed decreased perfusion in the cortex but increased perfusion in the deep brain regions compared with HCs. The regions with significant hypoperfusion were distributed in the bilateral frontal, temporal, parietal, and occipital gyri, with the left frontal gyrus being the most prominent. The regions with significant hyperperfusion included the bilateral basal ganglia, midbrain, pons, para-hippocampal, and parts of the bilateral cerebellum, fusiform, lingual, rectus, orbital, and cingulum anterior gyri, which were adjacent to the midline (all FDR-corrected p &lt;0.05). When comparing the mean CBF value of the whole brain, no significant differences were observed between NIID patients and HCs (28.81 ± 10.1 vs. 27.99 ± 5.68 ml/100 g*min, p = 0.666). Voxel-based analysis showed no significant difference in cerebral perfusion between NIID patients with and without episodic symptoms. The perfusion within the bilateral middle frontal and anterior cingulate gyri showed positive correlations with MMSE and MoCA scores using age, sex, and education as covariates (p &lt;0.005 uncorrected).ConclusionNIID patients exhibited characteristic cortical hypoperfusion and deep brain hyperperfusion. The perfusion in the bilateral frontal lobe and cingulate gyrus was correlated with the severity of cognitive dysfunction. Cerebral perfusion change may be involved in NIID pathophysiology and serve as a potential indicator for monitoring NIID severity and progression.
Protective effects and potential mechanisms of fermented egg-milk peptides on the damaged intestinal barrier
Authors: Lyu Siwen , Yang Qi , Duan Xuehui , Liu Xuanting , Du Zhiyang , Shang Xiaomin , Xu Menglei , Liu Jingbo , Pan Fengguang , Zhang Ting 
Published: December 2022

IntroductionFermented egg-milk peptides (FEMPs) could enhance the colon-intestinal barrier and upgrade the expression of zonula occludens-1 and mucin 2. Besides, the underlying biological mechanism and the targets FEMPs could regulate were analyzed in our study.MethodsHerein, the immunofluorescence technique and western blot were utilized to evaluate the repair of the intestinal barrier. Network pharmacology analysis and bioinformatics methods were performed to investigate the targets and pathways affected by FEMPs.Results and discussionAnimal experiments showed that FEMPs could restore intestinal damage and enhance the expression of two key proteins. The pharmacological results revealed that FEMPs could regulate targets related to kinase activity, such as AKT, CASP, RAF, and GSK. The above targets could interact with each other. GO analysis indicated that the targets regulated by FEMPs could participate in the kinase activity of the metabolic process. KEGG enrichment revealed that the core targets were enriched in pathways related to cell apoptosis and other important procedures. Molecular docking demonstrated that FEMPs could bind to the key target AKT via hydrogen bond interactions. Our study combined the experiment in vivo with the method in silico and investigated the interaction between peptides and targets in a pattern of multi-targets and multi-pathways, which offered a new perspective on the functional validation and potential application of bioactive peptides.
Case report: Two unique cases of co-existing primary brain tumors of glial origin in opposite hemispheres
Authors: Singhal Ishan , Coss Dylan , Mueller Wade , Straza Michael , Krucoff Max Ostrinsky , Santos-Pinheiro Fernando 
Published: December 2022

BackgroundPrimary CNS tumors are rare. Coexistence of two glial tumors of different histological origins in the same patient is even rarer. Here we describe two unique cases of coexisting distinct glial tumors in opposite hemispheres.CasesPatient 1 is a 38-year-old male who presented with a seizure in February/2016. MRI showed a left parietal and a right frontal infiltrating nonenhancing lesions. Both lesions were resected revealing an oligodendroglioma WHO grade-2 and an astrocytoma WHO grade-2. Patient 2 is a 34-year-old male who presented with a seizure in November/2021. MRI showed a left frontal and a right mesial temporal lobe infiltrating nonenhancing lesions. Both lesions were resected revealing an oligodendroglioma WHO grade-2 and a diffuse low-grade glioma, MAPK pathway-altered (BRAF V600E-mutant). Patient 1 underwent adjuvant treatment. Both patients are without recurrence to date.DiscussionTwo histologically distinct glial tumors may coexist, especially when they are non-contiguous. Pathological confirmation of each lesion is imperative for appropriate management. We highlight the different management of gliomas based on the new CNS WHO 2021 classification compared to its 2016 version, based on NCCN guidelines. Although more molecular markers are being incorporated into glioma classification, their clinical impact of it is yet to be determined.