Serum NfL and EGFR/NfL ratio mRNAs as biomarkers for phenotype and disease severity of myelin oligodendrocyte glycoprotein IgG-associated disease.

Background and purpose: Myelin oligodendrocyte glycoprotein (MOG) IgG is frequently elevated in pediatric patients with acquired demyelinating syndrome (ADS). However, no specific biomarkers exist for phenotype classification, symptom severity, prognosis, and treatment guidance of MOG-IgG-associated disease (MOGAD). This study evaluated neurofilament light chain (NfL) and endothelial growth factor receptor (EGFR) mRNA expression levels in serum and cerebrospinal fluid (CSF) as potential biomarkers for MOGAD in Chinese children. Methods: This was a cross-sectional and single-center study. We enrolled 22 consecutive pediatric patients hospitalized with MOGAD and 20 control pediatric patients hospitalized for noninflammatory neurological diseases in Hebei Children's Hospital. Serum and CSF were collected from MOGAD patients within 3 days before immunotherapy. The mRNA levels of NfL and EGFR in serum and CSF were measured by real-time polymerase chain reaction (qPCR), and the EGFR/NfL ratio mRNA was calculated. These measurement values were then compared between disease groups and among MOGAD phenotypes. In addition, the correlations between the mRNAs of three markers (NfL, EGFR, EGFR/NfL ratio), extended disability status scale (EDSS) scores, and clinical phenotypes were analyzed. Results: Serum and CSF NfL mRNA levels were significantly higher of acute-stage MOGAD patients than those of control patients (p< 0.05 and p< 0.01, respectively), while the mRNA levels of serum EGFR and EGFR/NfL ratio were significantly lower of MOGAD patients than those of controls (p < 0.05, p < 0.0001). Serum NfL mRNA was significantly correlated with mRNA of serum EGFR (r =0.480, p < 0.05). Serum and CSF NfL mRNA levels in MOGAD patients with the ADEM-like phenotype were also significantly higher than those in control patients (p < 0.01, p < 0.01) and optic neuritis (ON) phenotype (p < 0.05, p < 0.05). Both mRNAs of NfL in CSF and EGFR/NfL ratio in serum were correlated with EDSS scores (p < 0.05, r = 0.424; p < 0.05, r= -0.521). Conclusion: The mRNA levels of elevated NfL in serum and CSF as well as lower EGFR and EGFR/NfL ratio in serum could help distinguish acute-phase MOGAD. Higher mRNA levels of NfL in serum and CSF of MOGAD patients help distinguish ADEM-like phenotype. In addition, serum EGFR/NfL mRNA ratio is indicative of disease severity in pediatric patients with MOGAD. Further investigations are warranted to elucidate the pathological mechanisms underlying these associations.

A Nomogram for Predicting the Risk of Deep Vein Thrombosis in Patients With Acute Ischemic Stroke During the COVID-19.

Deep vein thrombosis (DVT) is an important complication of stroke. As coronavirus disease 2019 (COVID-19) enters the stage of persistent and long-term management, the clinical management of DVT in stroke patients may require adjustment. The present study evaluated whether there was an increased risk of DVT in stroke patients during the COVID-19 period. Furthermore, we analyzed the possible risk factors and developed an easy-to-use nomogram to predict DVT in stroke patients during the long-term management of COVID-19. A total of 7087 stroke patients during the COVID-19 period and 14,174 patients with age, sex, and National Institutes of Health Stroke Scale (NIHSS) scores matched before the period from four centers were included. The incidence of DVT in stroke patients during the COVID-19 period (20.5%) was significantly higher than that before this period (15.9%, P < .001). Age, body mass index, smoking, D-dimer, physical activity level, NIHSS score, and intermittent pneumatic compression were significant predictors of DVT during the COVID-19 period (P < .05). A nomogram was constructed; internal and external validations showed high accuracy, and decision curve analysis showed excellent clinical applicability. This nomogram could evaluate the risk of DVT after stroke and assist in its early prevention during the long-term management of COVID-19.

Event-related potentials in response to early terminated and completed sequential decision-making.

The process of outcome evaluation effectively navigates subsequent choices in humans. However, it is largely unclear how people evaluate decision outcomes in a sequential scenario, as well as the neural mechanisms underlying this process. To address this research gap, the study employed a sequential decision task in which participants were required to make a series of choices in each trial, with the option to terminate their choices. Based on participants' decisions, two outcome patterns were classified: the "reached" condition and the "unreached" condition, and the event-related potentials (ERPs) were recorded. Further, in the unreached condition, we investigated how the distance (i.e., the position interval between the actual outcome and potential outcome) modulated outcome evaluation. Behavioral data showed a higher emotion rating when people got a reward rather than a loss (i.e., the reached condition), while the opposite was true in the unreached condition. ERP results showed a larger feedback-related negativity (FRN), a smaller P3, and a larger late positive potential (LPP) when people got a loss compared to a reward. Importantly, a hierarchical processing pattern was found in the unreached condition: people processed separately the potential outcome and the distance at the early stage, manifested in the FRN amplitude; subsequently, the brain focused on the distance-a lower distance elicited an enhanced P3 amplitude. Finally, the potential outcome and distance were processed interactively in the LPP amplitude. Overall, these findings shed light on the neural underpinnings of outcome evaluation in sequential decision-making.

Spatiotemporal variations of heavy metal historical accumulation records and their influencing mechanisms in the Yangtze River Estuary.

Complex transformations of heavy metals in the mega-river-estuary continuum limit our understanding of their pollution history. This study investigated sedimentary compositions of heavy metals, major elements, total organic carbon, grain size, and radionuclides to study spatiotemporal variations in heavy metal accumulation patterns and their controlling mechanisms in four sediment cores (E1-E4) from the Yangtze River Estuary (YRE). Results show that only E3 in the distal YRE front mirrors well the heavy metal pollution history due to its continuous deposition in a stable sedimentary environment, while E1 and E2 record the influence of riverine and estuarine projects and processes apparently. E1 in the proximal YRE front registers intense human disturbance through sediment dredging and dumping activities to produce a thick layer of abnormal low 210Pbex and minor heavy metal concentrations. E2 in the intermediate YRE front demonstrates the recently increasing influence of reduced sediment discharge by its upcore coarsening trend with decreased heavy metal concentrations. Flood and storm events left different imprints in core sediments of E2 and E3 by their coarse stratal units with fewer heavy metal concentrations. The source analysis indicates that heavy metals in estuarine sediments mainly come from natural processes but are significantly affected by human activities. A direct linkage of the heavy metal accumulation history with the socioeconomic development in recent decades is found by a comparison study of core data from the tidal river to the estuary, albeit with a remarkable spatiotemporal difference, which is jointly determined by grain size, offshore distance, hydrodynamic condition, depositional status, and sedimentation rate besides estuarine processes. This warns us to carefully interpret the heavy metal history from single or sparse core data in a mega estuary system with intense natural forces and human disturbances analogous to the YRE.

Diagnosis by Endoscopic Ultrasonography-Guided Sampling through the Lower Gastrointestinal Tract.

Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) is very safe and has a high diagnostic rate for upper gastrointestinal lesions, especially pancreatic lesions, but its application in the lower gastrointestinal tract has rarely been reported. Due to the tortuous course of the colorectum, with the sigmoid colon particularly prone to perforation, most endoscopists are reluctant to perform lateral-sector endoscopic ultrasound scanning without a water-bag protection for the puncture. The ultrasonic endoscopy and flexible puncture needle techniques recently introduced into clinical practice have made ultrasound-guided puncture safer and more convenient. In addition, endoscopists have carefully tested various protective measures to improve the safety of the lower gastrointestinal puncture, substantially increasing its clinical feasibility. In this article, we review the iterations of endoscopic ultrasound equipment introduced in recent years and the many ingenious ideas proposed by endoscopists regarding lower gastrointestinal puncture.

Development of Irinotecan Liposome Armed with Dual-Target Anti-Epidermal Growth Factor Receptor and Anti-Fibroblast Activation Protein-Specific Antibody for Pancreatic Cancer Treatment.

Pancreatic cancer is one of the most common causes of death in Taiwan. Previous studies have shown that more than 90% of pancreatic cancer cells presented epidermal growth factor receptor (EGFR) cell marker, and this marker is thought to be important as it is related to activation of cancer cell proliferation, angiogenesis, and cancer progression. Moreover, tumor-associated fibroblasts were involved in tumor proliferation and progression. In this study, we fabricated an anti-EGFR and anti-fibroblast activation protein bispecific antibody-targeted liposomal irinotecan (BS-LipoIRI), which could specifically bind to pancreatic cancer cells and tumor-associated fibroblasts. The drug encapsulation efficiency of BS-LipoIRI was 80.95%, and the drug loading was 8.41%. We proved that both pancreatic cancer cells and fibroblasts could be targeted by BS-LipoIRI, which showed better cellular uptake efficacy compared to LipoIRI. Furthermore, an in vivo mouse tumor test indicated that BS-LipoIRI could inhibit pancreatic cancer growth up to 46.2% compared to phosphate-buffered saline control, suggesting that BS-LipoIRI could be useful in clinical cancer treatment.

Comparisons make faces more attractive: An ERP study.

Facial attractiveness judgment largely depends on the characteristics of the facial structure and the personality of the observer. However, little is known about the influence of contextual variations on facial attractiveness. In this electroencephalogram study, participants judged the attractiveness of faces presented individually or in pairs with either a higher-attractive face (HAF) or lower-attractive face (LAF). The attractiveness judgment rating of the target face was significantly higher when presented in pairs with HAFs or LAFs than when presented individually and was accompanied by a larger late positive complex. These results suggest that contextual faces enhance the attractiveness judgment of target faces. Microstate analyses revealed that the global field power (GFP) of state 3 was significantly correlated with the attractiveness judgment in the HAF condition whereas the GFP of state 2 was significantly correlated with the attractiveness judgment in the LAF condition. Interestingly, the GFP of state 2 mediated the relationship between narcissism and facial attractiveness judgment in the context of LAFs. Source location analyses showed that states 3 and 2 activated the superior and middle frontal gyrus, which are involved in emotion processing. Our findings suggest that facial attractiveness can be enhanced by contextual comparison with other faces, subject to personality of the observer.

Neural dynamics and coupling underlying uncertain anticipatory conflicts in anxious individuals.

Anticipation plays an important role in cognitive control and related psychiatric disorders such as anxiety. However, anticipation processing of conflicts in anxious individuals and the underlying brain mechanisms remain unknown. Using a newly designed cue-flanker task, we observed faster responses to congruent flankers with certain cues in individuals with high trait anxiety (HTA) than those with low trait anxiety (LTA). Microstate analyses revealed less occurrence of cue-evoked microstates in HTA than LTA. Importantly, the less occurrence of specific state was correlated to the larger flanker effect in HTA, suggesting that deficient conflict control in anxiety is associated with abnormal vigilance-related dynamic processing during anticipation. Delta-beta coupling at anticipation stage mediated the association between the level of anxiety and reaction time in conflict processing with uncertain cues in HTA, suggesting the mediatory role of delta-beta coupling in anticipatory conflict processing of anxious individuals. These results suggest hyperactive anticipatory processing of goal-relevant information for the upcoming conflict in anxious individuals. Our findings provide neurocognitive evidence for altered anticipatory cognitive control in anxious individuals and have important implications for diagnosis and treatment of anxiety-related disorders.

Ultrasonic optic nerve sheath diameter could improve the prognosis of acute ischemic stroke in the intensive care unit.

Objectives: Stroke patients with high intracranial pressure (ICP) may have poor prognosis. Non-invasive ultrasonic optic nerve sheath diameter (ONSD) could evaluate increased ICP. To investigate whether ONSD is valuable for prognosis of patients with acute ischemic stroke (AIS). Methods: AIS receiving intensive care were recruited with the Glasgow Coma Scale (GCS) score. Patients in group A underwent ultrasonic ONSD to assess ICP voluntarily, whereas group B without ONSD. Patients were followed up at discharge and once a week for 3 months with Glasgow Outcome Scale (GOS) score (four to five scores indicated good prognosis and one to three scores indicated poor prognosis). Results: Forty-nine patients were included. GCS scores did not differ significantly between groups A (26 patients) and B (8 ± 3 vs. 7 ± 3, p < 0.05). In group A, ONSD was 5.01 ± 0.48 mm, which correlated with GCS score (p < 0.05). At discharge, the GOS score was higher in group A than in group B (3.35 ± 1.35 vs. 2.57 ± 1.121, p = 0.034). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 13.0%, p = 0.006). At discharge and after 3 months of follow-up, ONSD at admission was correlated with the GOS score in group A (r = -0.648 [p < 0.05] and -0.731 [p < 0.05], respectively). After 3 months of follow-up, the GOS score was higher in group A than group B (3.00 ± 1.673 vs. 2.04 ± 1.430, p < 0.05). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 21.2%, p = 0.039). The Kaplan-Meier curve showed a higher rate of good prognosis in group A than in group B. ONSD (p < 0.05) was an independent predictor of poor prognosis. Conclusion: Non-invasive ultrasonic ONSD could be useful in improving the prognosis of patients with AIS receiving intensive care.

[Effects of two common acellular methods on the physicochemical properties of dermal acellular matrix].

At present, acellular matrix is an effective replacement material for the treatment of skin damage, but there are few systematic evaluation studies on its performance. The experimental group of this study used two decellularization methods to prepare the matrix: one was the acellular matrix which sterilized with peracetic acid first (0.2% PAA/4% ethanol solution) and then treated with hypertonic saline (group A), the other was 0.05% trypsin/EDTA decellularization after γ irradiation (group B); and the control group was soaked in PBS (Group C). Then physical properties and chemical composition of the three groups were detected. Hematoxylin eosin (HE) staining showed that the acellular effect of group B was good. The porosity of group A and B were both above 84.9%. In group A, the compressive modulus of elasticity was (9.94 ± 3.81) MPa, and the compressive modulus of elasticity was (12.59 ± 5.50) MPa in group B. There was no significant difference between group A or B and group C. The total content of collagen in acellular matrix of group A and B was significantly lower than that of group C (1. 662 ± 0.229) mg/g, but there was no significant difference in the ratio of collagen Ⅰ/Ⅲ between group B and group C. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that there was no significant difference in microstructure. Qualitative detection of fibronectin and elastin in each group was basically consistent with that in group C. Therefore, acellular matrix of group B had better performance as scaffold material. The experimental results show that the acellular matrix prepared by γ-ray sterilization and decellularization of 0.05% Trypsin enzyme/EDTA could be used for the construction of tissue-engineered skin. It could also provide reference for the preparation and mounting of heterogeneous dermal acellular matrix. It was also could be used for electrostatic spinning or three-dimensional printed tissue engineered skin scaffold which could provide physical and chemical parameters for it.

Underestimated heavy metal pollution of the Minjiang River, SE China: Evidence from spatial and seasonal monitoring of suspended-load sediments.

Previous assessments on rivers in SE China with highly developed economy and enormous population indicate diverse and relatively low particulate heavy metal pollution levels. However, the controlling mechanisms for heavy metal enrichment and transport remain enigmatic. Here, we target a mesoscale mountainous river, the Minjiang River, and obtain grain size, mineralogical and heavy metal concentration (Pb, Cd, Cr, Mn, Mo, Zn, V, Co, Ni, Cu) data from seasonal suspended particulate matter (SPM) near the river mouth, riverbed sediments and SPM samples from mainstream and major tributaries of the river. The results indicate that SPM samples have higher particulate heavy metal concentrations than riverbed sediments collected in pairs. Heavy metal concentrations of Cd, Zn, Cr, V, Co, Ni and Cu are higher in upstream SPM samples than those in downstream regions, whereas Pb, Mn and Mo concentrations don't show this spatial variation. Most heavy metals (e.g., Pb and Zn) show high concentrations in flood seasons and relatively low concentrations in dry seasons, revealing a hydrologic control. However, Cr and Mn show high concentrations in some dry season samples, suggesting incidental anthropogenic input events. The SPM-based pollution assessments using enrichment factor, geoaccumulation index and potential ecological risk index demonstrate that the Minjiang River is moderately to strongly polluted by particulate Pb, Cd, Mo and Zn contaminations and most particulate heavy metals have moderate to considerable potential ecological risks. We contend that transport and discharge of particulate heavy metals by the Minjiang River are controlled by both natural and anthropogenic forcings and the pollution levels are worse than previously known. Our findings suggest that particulate heavy metal discharge by subtropical mountainous rivers is related to sediment types and hydrologic characteristics. Therefore, high-spatiotemporal-resolution investigations on river SPM samples are highly recommended to better evaluate particulate heavy metal pollution levels and aquatic environmental conditions.

Primary vocal cord aspergillosis caused by Aspergillus fumigatus and molecular identification of the isolate.

This is a case of vocal cord aspergillosis in a 36-year-old woman whose chief complaint was progressive hoarseness and vocal fatigue of one month duration. These symptoms followed the use of systemic administration of penicillin, cefotaxime natrium and dexamethasone to treat her rhinitis and asthma. Fiberoptic laryngoscopy revealed whitish plaques involving both vocal cords. Microscopic examination of KOH preparations and histopathology studies of tissue revealed dichotomously branching, hyaline, septate hyphae. Morphological and molecular biological identification of the fungal growth in cultures inoculated with clinical specimens from the patient indicated that the etiologic agent was Aspergillus fumigatus. The patient was cured with oral itraconazole without any side effects.