Unlocking the age-old secrets of reward and substance use.

Although substance use is widespread across the lifespan from early adolescence to older adulthood, the prevalence of substance use disorder (SUD) differs between age groups. These age differences in SUD rates necessitate an investigation into how age moderates reward sensitivity, and consequently influences the risks and consequences related to substance use. This theoretical review integrates evidence from the literature to address the dynamic interplay between age and reward in the context of substance use. Overall, increasing evidence demonstrates that age moderates reward sensitivity and underlying reward system neurobiology. Reward sensitivity undergoes a non-linear trajectory across the lifespan. Low levels of reward sensitivity are associated with childhood and late adulthood. In contrast, high levels are associated with early to late adolescence, followed by a decline in the twenties. These fluctuations in reward sensitivity across the lifespan contribute to complex associations with substance use. This lends support to adolescence and young adulthood as vulnerable periods for the risk of subsequent SUD. More empirical research is needed to investigate reward sensitivity during SUD maintenance and recovery. Future research should also involve larger sample sizes and encompass a broader range of age groups, including older adults.

Characterization of the DUF868 gene family in Nicotiana and functional analysis of NtDUF868-E5 involved in pigment metabolism.

Domains of unknown function (DUF) proteins represent a large group of uncharacterized protein families. The DUF868 gene family in Nicotiana has not yet been described. In the present study, we identified 12, 11, and 25 DUF868 family members in the genome of Nicotiana sylvestris, N. tomentosiformis, and N. tabacum, respectively. Based on phylogenetic analysis, these were categorized into five groups (A-E). Within each group, the gene structures, motifs, and tertiary structures showed high similarity. NtDUF868 family expansion during evolution was mainly driven by segmental duplication events. MicroRNA (miRNA) target site prediction identified 12 miRNA members that target 16 NtDUF868 family genes. The promoters of these genes contain cis-regulatory elements responsive to light, phytohormones, and abiotic stresses. Expression profiling revealed their tissue- and stage-specific expression patterns. RNA-sequencing and quantitative reverse transcription PCR revealed that the NtDUF868 family genes are potentially involved in the response to abiotic and biotic stresses, particularly drought and hormone stresses, and in the resistance to black shank and bacterial wilt. We generated transformed plants using NtDUF868-E5 overexpression and gene-editing vectors. NtDUF868-E5 overexpression resulted in enhanced tobacco plant growth and development, leading to increased leaf photosynthetic capacity and higher chlorophyll and carotenoid contents. This study provided a comprehensive genome-wide analysis of the DUF868 gene family, shedding light on their potential roles in plant growth and stress responses.

Design and performance of an ultrahigh vacuum spectroscopic-imaging scanning tunneling microscope with a hybrid vibration isolation system.

A spectroscopic imaging-scanning tunneling microscope (SI-STM) allows for the atomic scale visualization of the surface electronic and magnetic structure of novel quantum materials with a high energy resolution. To achieve the optimal performance, a low vibration facility is required. Here, we describe the design and performance of an ultrahigh vacuum STM system supported by a hybrid vibration isolation system that consists of a pneumatic passive and a piezoelectric active vibration isolation stage. We present the detailed vibrational noise analysis of the hybrid vibration isolation system, which shows that the vibration level can be suppressed below 10-8 m/sec/√Hz for most frequencies up to 100 Hz. Combined with a rigid STM design, vibrational noise can be successfully removed from the tunneling current. We demonstrate the performance of our STM system by taking high resolution spectroscopic maps and topographic images on several quantum materials. Our results establish a new strategy to achieve an effective vibration isolation system for high-resolution STM and other scanning probe microscopies to investigate the nanoscale quantum phenomena.

Construction and characterization of an infectious cDNA clone of human rhinovirus A89.

Rhinoviruses (RVs) are major causes of the common cold and are related to severe respiratory tract diseases, leading to a considerable economic burden and impacts on public health. Available and stable viral resources of rhinoviruses for laboratory use are important for promoting studies on rhinoviruses and further vaccine or therapeutic drug development. Reverse genetic technology can be useful to produce rhinoviruses and will help to promote studies on their pathogenesis and virulence. In this study, rhinovirus A89, an RV-A species that has been found to be highly involved in hospitalization triggered by RV infections, was selected to construct an infectious clone based on its sequence as a representative. The viral mRNA produced by a T7 RNA transcript system was transfected into H1-HeLa cells, and the rescued RV-A89 viruses were harvested and confirmed by sequencing. The rescued RV-A89 induced a similar cytopathic effect (CPE) and shared almost identical growth kinetics curves with parental RV-A89. Moreover, 9A7, a prescreened monoclonal antibody against the parental RV-A89, had a good and specific reaction with the rescued RV-A89, and further characterization showed almost the same morphology and protein composition of both viruses; thus, recombinant RV-A89 with similar biological characterization and virulence to the parental virus was obtained. In summary, the infectious clone of RV-A89 was successfully established, and the development of reverse genetic technology for rhinovirus will provide a framework for further studies on rhinoviruses.

Evaluation of the efficiency, trueness, and clinical application of novel artificial intelligence design for dental crown prostheses.

OBJECTIVE: The unique structure of human teeth limits dental repair to custom-made solutions. The production process requires a lot of time and manpower. At present, artificial intelligence (AI) has begun to be used in the medical field and improve efficiency. This study attempted to design a variety of dental restorations using AI and evaluate their clinical applicability. METHODS: Using inlay and crown restoration types commonly used in dental standard models, we compared differences in artificial wax-up carving (wax-up), artificial digital designs (digital) and AI designs (AI). The AI system was designed using computer calculations, and the other two methods were designed by humans. Restorations were made by 3D printing resin material. Image evaluations were compared with cone beam computed tomography (CBCT) by calculating the root mean squared error. RESULTS: Surface truth results showed that AI (68.4 µm) and digital-designed crowns (51.0 µm) had better reproducibility. Using AI for the crown reduced the time spent by 400% (compared to digital) and 900% (compared to wax-up). Optical microscopic and CBCT images showed that AI and digital designs had close margin gaps (p < 0.05). The margin gap of the crown showed that the wax-up group was 4.1 and 4.3 times greater than those of the AI and digital crowns, respectively. Therefore, the utilization of artificial intelligence can assist in the production of dental restorations, thereby enhancing both production efficiency and accuracy. SIGNIFICANCE: It is expected that the development of AI can contribute to the reproducibility, efficiency, and goodness of fit of dental restorations.

Investigating the virulence of coxsackievirus B6 strains and antiviral treatments in a neonatal murine model.

Coxsackievirus B6 (CVB6), a member of the human enterovirus family, is associated with severe diseases such as myocarditis in children. However, to date, only a limited number of CVB6 strains have been identified, and their characterization in animal models has been lacking. To address this gap, in this study, a neonatal murine model of CVB6 infection was established to compare the replication and virulence of three infectious-clone-derived CVB6 strains in vivo. The results showed that following challenge with a lethal dose of CVB6 strains, the neonatal mice rapidly exhibited a series of clinical signs, such as weight loss, limb paralysis, and death. For the two high-virulence CVB6 strains, histological examination revealed myocyte necrosis in skeletal and cardiac muscle, and immunohistochemistry confirmed the expression of CVB6 viral protein in these tissues. Real-time PCR assay also revealed higher viral loads in the skeletal and cardiac muscle than in other tissues at different time points post infection. Furthermore, the protective effect of passive immunization with antisera and a neutralizing monoclonal antibody against CVB6 infection was evaluated in the neonatal mouse model. This study should provide insights into the pathogenesis of CVB6 and facilitate further research in the development of vaccines and antivirals against CVBs.

Comparative analysis of codon usage patterns of Plasmodium helical interspersed subtelomeric (PHIST) proteins.

Background: Plasmodium falciparum is a protozoan parasite that causes the most severe form of malaria in humans worldwide, which is predominantly found in sub-Saharan Africa, where it is responsible for the majority of malaria-related deaths. Plasmodium helical interspersed subtelomeric (PHIST) proteins are a family of proteins, with a conserved PHIST domain, which are typically located at the subtelomeric regions of the Plasmodium falciparum chromosomes and play crucial roles in the interaction between the parasite and its human host, such as cytoadherence, immune evasion, and host cell remodeling. However, the specific utilization of synonymous codons by PHIST proteins in Plasmodium falciparum is still unknown. Methods: Codon usage bias (CUB) refers to the unequal usage of synonymous codons during translation, resulting in over- or underrepresentation of certain nucleotide patterns. This imbalance in CUB can impact various cellular processes, including protein expression levels and genetic variation. To investigate this, the CUB of 88 PHIST protein coding sequences (CDSs) from 5 subgroups were analyzed in this study. Results: The results showed that both codon base composition and relative synonymous codon usage (RSCU) analysis identified a higher occurrence of AT-ended codons (AGA and UUA) in PHIST proteins of Plasmodium falciparum. The average effective number of codons (ENC) for these PHIST proteins was 36.69, indicating a weak codon preference among them, as it was greater than 35. Additionally, the correlation analysis among codon base composition (GC1, GC2, GC3, GCs), codon adaptation index (CAI), codon bias index (CBI), frequency of optimal codons (FOP), ENC, general average hydropathicity (GRAVY), aromaticity (AROMO), length of synonymous codons (L_sym), and length of amino acids (L_aa) revealed the influence of base composition and codon usage indices on codon usage bias, with GC1 having a significant impact in this study. Furthermore, the neutrality plot analysis, PR2-bias plot analysis, and ENC-GC3 plot analysis provided additional evidence that natural selection plays a crucial role in determining codon bias in PHIST proteins. Conclusion: In conclusion, this study has enhanced our understanding of the characteristics of codon usage and genetic evolution in PHIST proteins, thereby providing data foundation for further research on antimalarial drugs or vaccines.

Spectral Cross-Domain Neural Network With Soft-Adaptive Threshold Spectral Enhancement.

Electrocardiography (ECG) signals can be considered as multivariable time series (TS). The state-of-the-art ECG data classification approaches, based on either feature engineering or deep learning techniques, treat separately spectral and time domains in machine learning systems. No spectral-time domain communication mechanism inside the classifier model can be found in current approaches, leading to difficulties in identifying complex ECG forms. In this article, we proposed a novel deep learning model named spectral cross-domain neural network (SCDNN) with a new block called soft-adaptive threshold spectral enhancement (SATSE), to simultaneously reveal the key information embedded in spectral and time domains inside the neural network. More precisely, the domain-cross information is captured by a general convolutional neural network (CNN) backbone, and different information sources are merged by a self-adaptive mechanism to mine the connection between time and spectral domains. In SATSE, the knowledge from time and spectral domains is extracted via the fast Fourier transformation (FFT) with soft trainable thresholds in modified sigmoid functions. The proposed SCDNN is tested with several classification tasks implemented on the public ECG databases PTB-XL and CPSC2018. SCDNN outperforms the state-of-the-art approaches with a low computational cost regarding a variety of metrics in all classification tasks on both databases, by finding appropriate domains from the infinite spectral mapping. The convergence of the trainable thresholds in the spectral domain is also numerically investigated in this article. The robust performance of SCDNN provides a new perspective to exploit knowledge across deep learning models from time and spectral domains. The code repository can be found: https://github.com/DL-WG/SCDNN-TS.

Downregulation of VEGFR2 signaling by cedrol abrogates VEGF­driven angiogenesis and proliferation of glioblastoma cells through AKT/P70S6K and MAPK/ERK1/2 pathways.

Cedrol is a sesquiterpene alcohol isolated from Cedrus atlantica, which has been traditionally used in aromatherapy and has anticancer, antibacterial and antihyperalgesic effects. One characteristic of glioblastoma (GB) is the overexpression of vascular endothelial growth factor (VEGF), which induces a high degree of angiogenesis. Although previous studies have reported that cedrol inhibits GB growth by inducing DNA damage, cell cycle arrest and apoptosis, its role in angiogenesis remains unclear. The aim of the present study was to investigate the effects of cedrol on VEGF-induced angiogenesis of human umbilical vein endothelial cells (HUVECs). HUVECs were treated with 0-112 µM cedrol and 20 ng/ml VEGF for 0-24 h, and then anti-angiogenic activation of cedrol was determined by MTT assay, wound healing assay, Boyden chamber assay, tube formation assay, semi-quantitative reverse transcription-PCR and western blotting. These results demonstrated that cedrol treatment inhibited VEGF-induced cell proliferation, migration and invasion in HUVECs. Furthermore, cedrol prevented VEGF and DBTRG-05MG GB cells from inducing capillary-like tube formation in HUVECs and decreased the number of branch points formed. Moreover, cedrol downregulated the phosphorylation of VEGF receptor 2 (VEGFR2) and the expression levels of its downstream mediators AKT, ERK, VCAM-1, ICAM-1 and MMP-9 in HUVECs and DBTRG-05MG cells. Taken together, these results demonstrated that cedrol exerts anti-angiogenic effects by blocking VEGFR2 signaling, and thus could be developed into health products or therapeutic agents for the prevention or treatment of cancer and angiogenesis-related diseases in the future.

Mortality Evaluation and Life Expectancy Prediction of Patients with Hepatocellular Carcinoma with Data Mining.

BACKGROUND: The complexity of systemic variables and comorbidities makes it difficult to determine the best treatment for patients with hepatocellular carcinoma (HCC). It is impossible to perform a multidimensional evaluation of every patient, but the development of guidelines based on analyses of said complexities would be the next best option. Whereas conventional statistics are often inadequate for developing multivariate predictive models, data mining has proven more capable. Patients, methods and findings: Clinical profiles and treatment responses of 537 patients diagnosed with Barcelona Clinic Liver Cancer stages B and C from 2009 to 2019 were retrospectively analyzed using 4 decision tree algorithms. A combination of 19 treatments, 7 biomarkers, and 4 states of hepatitis was tested to determine which combinations would result in survival times greater than a year in duration. Just 2 of the algorithms produced complete models through single trees, which made them only the ones suitable for clinical judgement. A combination of alpha fetoprotein ≤210.5 mcg/L, glutamic oxaloacetic transaminase ≤1.13 µkat/L, and total bilirubin ≤ 0.0283 mmol/L was shown to be a good predictor of survival >1 year, and the most effective treatments for such patients were radio-frequency ablation (RFA) and transarterial chemoembolization (TACE) with radiation therapy (RT). In patients without this combination, the best treatments were RFA, TACE with RT and targeted drug therapy, and TACE with targeted drug therapy and immunotherapy. The main limitation of this study was its small sample. With a small sample size, we may have developed a less reliable model system, failing to produce any clinically important results or outcomes. CONCLUSION: Data mining can produce models to help clinicians predict survival time at the time of initial HCC diagnosis and then choose the most suitable treatment.

Sensitivity and Specificity of US and CT as Diagnostic Tools for Pediatric Lateral Neck Abscesses.

OBJECTIVE: Ultrasound (US) and computed tomography (CT) are commonly used in the diagnosis of pediatric neck abscesses. The objective of this study is to determine the sensitivity and specificity of US and CT in the diagnosis of pediatric lateral neck abscesses, with a secondary objective of evaluating the association of specific clinical features with a positive US or CT scan. STUDY DESIGN: Retrospective review of pediatric patients admitted to a tertiary care center from January 1, 2011, to December 31, 2020, with neck abscesses. SETTING: Tertiary care center. METHODS: The sensitivity and specificity of US and CT were calculated by comparing imaging performed within 24 h of incision and drainage (I&D). Multiple regression was used to evaluate the association of clinical features with a true positive US or CT. RESULTS: There were 171 patients included in this study, with a median age of 1.5 years (interquartile range [IQR]: 1-5 years). I&D was done in 156 patients (91.2%), while 15 (8.8%) were treated with antibiotics. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US were 69.5%, 80%, 96.6%, and 24.2%. The sensitivity, specificity, PPV, and NPV of neck CT were 95.5%, 80%, 95.5%, and 57.1%. Length of symptoms, skin erythema, and fluctuance were not significantly associated with a positive US (F(3, 82) = 0.24, p = .9, R2 = 0.01) or CT scan (F(3, 30) = 0.84, p = .5, R2 = 0.08). CONCLUSION: Neck US has a low sensitivity for diagnosing pediatric neck abscesses, when compared to CT, but remains a useful initial investigation given its high PPV. Clinicians should have a low threshold for pursuing CT if there is a high suspicion of abscess formation. LEVEL OF EVIDENCE: Level 4.

Intelligent metasurface system for automatic tracking of moving targets and wireless communications based on computer vision.

The fifth-generation (5G) wireless communication has an urgent need for target tracking. Digital programmable metasurface (DPM) may offer an intelligent and efficient solution owing to its powerful and flexible controls of electromagnetic waves and advantages of lower cost, less complexity and smaller size than the traditional antenna array. Here, we report an intelligent metasurface system to perform target tracking and wireless communications, in which computer vision integrated with a convolutional neural network (CNN) is used to automatically detect the locations of moving targets, and the dual-polarized DPM integrated with a pre-trained artificial neural network (ANN) serves to realize the smart beam tracking and wireless communications. Three groups of experiments are conducted for demonstrating the intelligent system: detection and identification of moving targets, detection of radio-frequency signals, and real-time wireless communications. The proposed method sets the stage for an integrated implementation of target identification, radio environment tracking, and wireless communications. This strategy opens up an avenue for intelligent wireless networks and self-adaptive systems.

Early Amnestic Mild Cognitive Impairment Is Associated with Reduced Total Cerebral Blood Flow with no Brain Tissue Loss.

BACKGROUND: Lower cerebral blood flow (CBF) and excessive brain atrophy are linked to Alzheimer's disease (AD). It is still undetermined whether reduced CBF precedes or follows brain tissue loss. OBJECTIVE: We compared total CBF (tCBF), global cerebral perfusion (GCP), and volumes of AD-prone regions between cognitively normal (CN) and early amnestic mild cognitive impairment (aMCI) and tested their associations with cognitive performance to assess their predictive value for differentiation between CN and early aMCI. METHODS: A total of 74 participants (mean age 69.9±6.2 years, 47 females) were classified into two groups: 50 CN and 24 aMCI, of whom 88% were early aMCI. tCBF, GCP, and global and regional brain volumetry were measured using phase-contrast and T1-weighted MRI. Neuropsychological tests tapping global cognition and four cognitive domains (memory, executive function, language, and visuospatial) were administered. Comparisons and associations were investigated using analyses of covariance (ANCOVA) and linear regression analyses, respectively. RESULTS: Women had significantly higher GCP than men. Both, tCBF and GCP were significantly reduced in aMCI compared with CN, while differences in volumes of cerebral gray matter, white matter, and AD-prone regions were not significant. tCBF and GCP were significantly associated with global cognition (standardized beta (stß) = 0.324 and stß= 0.326) and with memory scores (stß≥0.297 and stß≥0.264) across all participants. Associations of tCBF and GCP with memory scores were also significant in CN (stß= 0.327 and stß= 0.284) and in aMCI (stß= 0.627 and stß= 0.485). CONCLUSION: Reduced tCBF and GCP are sensitive biomarkers of early aMCI that likely precede brain tissue loss.

Development and validation of a nomogram model for predicting the risk of gallstone recurrence after gallbladder-preserving surgery.

BACKGROUND: The high incidence of gallstone recurrence was a major concern for laparoscopic gallbladder-preserving surgery. This study aimed to investigate the risk factors for gallstone recurrence after gallbladder-preserving surgery and to establish an individualized nomogram model to predict the risk of gallstone recurrence. METHODS: The clinicopathological and follow-up data of 183 patients who were initially diagnosed with gallstones and treated with gallbladder-preserving surgery at our hospital from January 2012 to January 2019 were retrospectively collected. The independent predictive factors for gallstone recurrence following gallbladder-preserving surgery were identified by multivariate logistic regression analysis. A nomogram model for the prediction of gallstone recurrence was constructed based on the selected variables. The C-index, receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive power of the nomogram model for gallstone recurrence. RESULTS: During the follow-up period, a total of 65 patients experienced gallstone recurrence, and the recurrence rate was 35.5%. Multivariate logistic regression analysis revealed that the course of gallstones > 2 years [odds ratio (OR) = 2.567, 95% confidence interval (CI): 1.270-5.187, P = 0.009], symptomatic gallstones (OR = 2.589, 95% CI: 1.059-6.329, P = 0.037), multiple gallstones (OR = 2.436, 95% CI: 1.133-5.237, P = 0.023), history of acute cholecystitis (OR = 2.778, 95% CI: 1.178-6.549, P = 0.020) and a greasy diet (OR = 2.319, 95% CI: 1.186-4.535, P = 0.014) were independent risk factors for gallstone recurrence after gallbladder-preserving surgery. A nomogram model for predicting the recurrence of gallstones was established based on the above five variables. The results showed that the C-index of the nomogram model was 0.692, suggesting it was valuable to predict gallstone recurrence. Moreover, the calibration curve showed good consistency between the predicted probability and actual probability. CONCLUSIONS: The nomogram model for the prediction of gallstone recurrence might help clinicians develop a proper treatment strategy for patients with gallstones. Gallbladder-preserving surgery should be cautiously considered for patients with high recurrence risks.

Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.

SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

Effect of Whey Protein Supplementation in Postmenopausal Women: A Systematic Review and Meta-Analysis.

(1) Background: Whey protein (WP) in combination with resistance training (RT) is beneficial in improving sarcopenic obesity and its damaging effects in older adults, while the difference between men and women should be considered while interpreting results. This review aims to investigate WP's efficacy on postmenopausal women with or without RT; (2) Material and Methods: We searched electronic databases including PubMed, EMBASE, and the Cochrane Library from inception to August 2021 for randomized controlled trials that included comparison groups to evaluate WP's efficacy in women aged 55 years and above. The outcomes included body composition, muscular strength, functional capacity, and dietary intake. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to estimate the effect of WP. We also performed subgroup analysis with or without RT; (3) Results: We included 14 studies in the systematic review and 10 studies in the meta-analysis. Subgroup analyses showed RT was a major confounder for muscle strength, lean mass, and dietary protein intake (PI). In the RT subgroup, WP supplementation had a significant positive effect on biceps curl strength (BC) (SMD: 0.6805, 95% CI: 0.176, 1.185, I2: 0%), and lower limb lean-mass (LLLM) (SMD: 1.103, 95% CI: 0.632, 1.574, I2: 14%). In the subgroup without RT, a significant negative effect on PI (SMD: -0.4225, 95% CI: -0.774, -0.071, I2: 47%) was observed, while no significant effect on muscle strength or lean mass was revealed. WP supplementation did not show a significantly different effect on fat mass or body weight loss in both the subgroups; (4) Conclusions: In postmenopausal women, WP supplementation only in combination with RT enhances BC and LLLM compared to placebo controls. Without RT, WP has no significant benefit on muscle strength or lean mass.

Blood-Brain Barrier Disruption in Preclinical Mouse Models of Stroke Can Be an Experimental Artifact Caused by Craniectomy.

The pathophysiological features of ischemia-related blood-brain barrier (BBB) disruption are widely studied using preclinical stroke models. However, in many of these models, craniectomy is required to confirm arterial occlusion via laser Doppler flowmetry or to enable direct ligation of the cerebral artery. In the present study, mice were used to construct a distal middle cerebral artery occlusion (dMCAO) model, a preclinical stroke model that requires craniectomy to enable direct ligation of the cerebral artery, or were subjected to craniectomy alone. dMCAO but not craniectomy caused neurodegeneration and cerebral infarction, but both procedures induced an appreciable increase in BBB permeability to Evans blue dye, fluorescein, and endogenous albumin but not to 10 kDa dextran-FITC, leading to cerebral edema. Using rats, we further showed that BBB disruption induced by craniectomy with no evidence of dural tearing was comparable to that induced by craniectomy involving tearing of the dura. In conclusion, our data demonstrated that craniectomy can be a major contributor to BBB disruption and cerebral edema in preclinical stroke models. The implications of this experimental artifact for translational stroke research and preclinical data interpretation are discussed.

Zusammenhang zwischen bullösem Pemphigoid und psychiatrischen Erkrankungen: Eine systematische Übersicht und Metaanalyse.

HINTERGRUND UND ZIELE: Trotz des wohlbekannten Zusammenhangs zwischen bullösem Pemphigoid (BP) und neurologischen Erkrankungen ist der Zusammenhang zwischen BP und psychiatrischen Erkrankungen nach wie vor ungeklärt. In dieser Studie war es unser Ziel, den Zusammenhang zwischen BP und verschiedenen psychischen Störungen zu untersuchen. PATIENTEN UND METHODEN: Die Datenbanken PubMed, Embase und Cochrane Library wurden bis zum 30. Mai 2021 hinsichtlich der Identifizierung geeigneter Kohorten- und Fall-Kontroll-Studien durchsucht. Anschließend wurden Metaanalysen der rohen Schätzwerte sowie der bereinigten Schätzwerte der Odds-Ratio (OR) für Fall-Kontroll-Studien und der Hazard-Ratio (HR) für Kohortenstudien durchgeführt. ERGEBNISSE: Es wurden 16 Studien mit 637 285 Patienten in die qualitative Synthese eingeschlossen. In der Metaanalyse der bereinigten Schätzwerte für Fall-Kontroll-Studien zeigten Patienten mit BP eine signifikant höhere Prävalenz psychischer Störungen (OR 1,77, 95 %-Konfidenzintervall (KI) 1,07-2,92) und Schizophrenie (OR 2,63, 95 %-KI 2,03-3,39). Hinsichtlich der Analyse der bereinigten Schätzwerte für Kohortenstudien stellte BP kein signifikant höheres Risiko für Depression (HR 1,09, 95 %-KI 0,94-1,26) und Schizophrenie (HR 1,35, 95 %-KI 0,76-2,39) dar. SCHLUSSFOLGERUNGEN: Bei psychiatrischen Erkrankungen, insbesondere Schizophrenie, besteht ein signifikant höheres Risiko, dass sie einem BP vorausgehen.

Development of a rapid neutralization testing system for Rhinovirus C15 based on the enzyme-linked immunospot assay.

Human Rhinoviruses (RVs) are dominant pathogens causing a wide range of respiratory tract diseases, posing a huge threat to public health worldwide. Viruses belonging to the RV-C species are more likely to cause severe illnesses and are strongly associated with asthma onset or exacerbations than RV-A or RV-B. Rapid and sensitive detection of neutralizing antibodies (NAbs) against RV-C can promote the development of vaccines and antiviral drugs and help in the diagnosis of viral infection. In this study, a rapid neutralization testing system for RV-C15, based on an enzyme-linked immunospot assay (Nt-ELISPOT) was developed. A monoclonal antibody (MAb), named 9F9, with high binding efficacy for RV-C15 conjugated to horseradish peroxidase (HRP), was used to detect RV-C15-infected cells at a concentration of 2 µg/ml. The optimal infectious dose of RV-C15 was set at 1 × 104 TCID50/well and the cells were fixed with 0.5% formaldehyde diluted in PBS after incubation for 20 h. Compared with the traditional cytopathic effect (CPE)-based neutralization assay (Nt-CPE), Nt-ELISPOT significantly shortened the detection period and showed good consistency with the detection of neutralizing titers of both sera and NAbs. Using Nt-ELISPOT, three anti-RV-C15 NAbs were obtained with IC50 values of 0.16, 0.27, and 11.8 µg/ml, respectively. Moreover, 64 human serum samples collected from a wide range of age groups were tested for NAb against RV-C15 by Nt-ELISPOT. The total seroprevalence was 48.4% (31/64) and the positive rate was lowest in the group under 6 years old. Thus, the Nt-ELISPOT established in this study can be used as a high-throughput and rapid neutralization assay for the screening of NAbs and for seroepidemiological investigation against RV-C15.

Association between bullous pemphigoid and psychiatric disorders: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Despite the well-established association between bullous pemphigoid (BP) and neurological diseases, the association between BP and psychiatric disorders remains unclear. In this study, we aimed to investigate the association between BP and various psychiatric disorders. PATIENTS AND METHODS: PubMed, Embase, and Cochrane Library databases were searched for the identification of eligible cohort and case-control studies until May 30, 2021. Meta-analyses of crude estimates and adjusted estimates of odds ratio (OR) for case-control studies and hazard ratio (HR) cohort studies were then conducted. RESULTS: Sixteen studies involving 637,285 patients were included for the qualitative synthesis. In the meta-analysis of adjusted estimates for case-control studies, patients with BP exhibited a significantly higher prevalence of psychiatric disorders (OR 1.77, 95 % confidence interval (CI) 1.07-2.92) and schizophrenia (OR 2.63, 95 % CI 2.03-3.39). Regarding the analysis of adjusted estimates of cohort studies, BP presented no significantly higher risk of depression (HR 1.09, 95 % CI 0.94-1.26) and schizophrenia (HR 1.35, 95 % CI 0.76-2.39). CONCLUSIONS: Psychiatric disorders, especially schizophrenia, have a significantly higher risk of preceding BP.