Preventive and therapeutic effects of a super-multivalent sialylated filamentous bacteriophage against the influenza virus.

The resurgence of influenza viruses as a significant global threat emphasizes the urgent need for innovative antiviral strategies beyond existing treatments. Here, we present the development and evaluation of a novel super-multivalent sialyllactosylated filamentous phage, termed t-6SLPhage, as a potent entry blocker for influenza A viruses. Structural variations in sialyllactosyl ligands, including linkage type, valency, net charge, and spacer length, were systematically explored to identify optimal binding characteristics against target hemagglutinins and influenza viruses. The selected SLPhage equipped with optimal ligands, exhibited exceptional inhibitory potency in in vitro infection inhibition assays. Furthermore, in vivo studies demonstrated its efficacy as both a preventive and therapeutic intervention, even when administered post-exposure at 2 days post-infection, under 4 lethal dose 50% conditions. Remarkably, co-administration with oseltamivir revealed a synergistic effect, suggesting potential combination therapies to enhance efficacy and mitigate resistance. Our findings highlight the efficacy and safety of sialylated filamentous bacteriophages as promising influenza inhibitors. Moreover, the versatility of M13 phages for surface modifications offers avenues for further engineering to enhance therapeutic and preventive performance.

Neural correlates of anhedonia in young adults with subthreshold depression: A graph theory approach for cortical-subcortical structural covariance.

BACKGROUND: Anhedonia is an enduring symptom of subthreshold depression (StD) and predict later onset of major depressive disorder (MDD). Brain structural covariance describes the inter-regional distribution of morphological changes compared to healthy controls (HC) and reflects brain maturation and disease progression. We investigated neural correlates of anhedonia from the structural covariance. METHODS: T1-weighted brain magnetic resonance images were acquired from 79 young adults (26 StD, 30 MDD, and 23 HC). Intra-individual structural covariance networks of 68 cortical surface area (CSAs), 68 cortical thicknesses (CTs), and 14 subcortical volumes were constructed. Group-level hubs and principal edges were defined using the global and regional graph metrics, compared between groups, and examined for the association with anhedonia severity. RESULTS: Global network metrics were comparable among the StD, MDD, and HC. StD exhibited lower centralities of left pallidal volume than HC. StD showed higher centralities than HC in the CSAs of right rostral anterior cingulate cortex (ACC) and pars triangularis, and in the CT of left pars orbitalis. Less anhedonia was associated with higher centralities of left pallidum and right amygdala, higher edge betweenness centralities in the structural covariance (EBSC) of left postcentral gyrus-parahippocampal gyrus and LIPL-right amygdala. More anhedonia was associated with higher centralities of left inferior parietal lobule (LIPL), left postcentral gyrus, left caudal ACC, and higher EBSC of LIPL-left postcentral gyrus, LIPL-right lateral occipital gyrus, and left caudal ACC-parahippocampal gyrus. LIMITATIONS: This study has a cross-sectional design. CONCLUSIONS: Structural covariance of brain morphologies within the salience and limbic networks, and among the salience-limbic-default mode-somatomotor-visual networks, are possible neural correlates of anhedonia in depression.

Decreased Serum Cocaine- and Amphetamine-Regulated Transcript Level in Internet Gaming Disorder.

OBJECTIVE: Vulnerability to internet gaming disorder (IGD) has increased as internet gaming continues to grow. Cocaine- and amphetamine-regulated transcript (CART) is a hormone that plays a role in reward, anxiety, and stress. The purpose of this study was to identify the role of CART in the pathophysiology of IGD. METHODS: The serum CART levels were measured by enzyme-linked immunosorbent assay, and the associations of the serum CART level with psychological variables were analyzed in patients with IGD (n=31) and healthy controls (HC) (n=42). RESULTS: The serum CART level was significantly lower in the IGD than HC group. The IGD group scored significantly higher than the HC group on the psychological domains of depression, anxiety, the reward response in the Behavioral Activation System and Behavioral Inhibition System. There were no significant correlations between serum CART level and other psychological variables in the IGD group. CONCLUSION: Our results indicate that a decrease in the expression of the serum CART level is associated with the vulnerability of developing IGD. This study supports the possibility that CART is a biomarker in the pathophysiology of IGD.

Therapeutic Potential of Mangosteen Pericarp Extract-Loaded Liposomes against Superficial Skin Infection Caused by Staphylococcus pseudintermedius in a Murine Model.

α-mangostin (α-MG) demonstrates antibacterial activity against Staphylococcus species. Therefore, this study aimed to explore the antibacterial activity of α-MG-rich mangosteen pericarp extract (MPE)-loaded liposomes against Staphylococcus isolates from companion animal skin diseases in vitro and evaluated their therapeutic potential in a murine model of superficial skin infection caused by S. pseudintermedius. α-MG-rich extract was purified from mangosteen pericarp and then complexed with γ-cyclodextrin (γ-CD), forming the inclusion complexes. Nanoliposomes containing MPE and γ-CD complexes were prepared by adding lecithin and casein. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of MPE-loaded liposomes were determined using agar dilution and broth microdilution methods. The therapeutic potential of MPE-loaded liposomes was evaluated in vivo on tape-stripped skin lesions infected with S. pseudintermedius. Purified MPE and MPE-loaded liposomes contained 402.43 mg/g and 18.18 mg/g α-MG, respectively. MPE-loaded liposomes showed antibacterial activity against clinical Staphylococcus isolates in vitro but did not show antibacterial activity against Gram-negative bacterial isolates. MPE-loaded liposomes demonstrated consistent MICs and MBCs against Staphylococcus isolates. These liposomes significantly reduced bacterial numbers and lesional sizes in a superficial skin infection model. Moreover, they reconstructed the epidermal barrier in skin lesions. The therapeutic concentrations of MPE-loaded liposomes did not induce cytotoxicity in canine progenitor epidermal keratinocyte cells. In conclusion, MPE-loaded liposomes hold promise for the development of a prospective topical formulation to treat superficial pyoderma in companion animals.

Topological abnormalities of the morphometric similarity network of the cerebral cortex in schizophrenia.

A morphometric similarity (MS) network can be constructed using multiple magnetic resonance imaging parameters of each cortical region. An MS network can be used to assess the similarity between cortical regions. Although MS networks can detect microstructural alterations and capture connections between histologically similar cortical areas, the influence of schizophrenia on the topological characteristics of MS networks remains unclear. We obtained T1- and diffusion-weighted images of 239 healthy controls and 190 individuals with schizophrenia to construct the MS network. Group comparisons of the mean MS of the cortical regions and subnetworks were performed. The strengths of the connections between the cortical regions and the global and nodal network indices were compared between the groups. Clinical associations with the network indices were tested using Spearman's rho. Compared with healthy controls, individuals with schizophrenia had significant group differences in the mean MS of several cortical regions and subnetworks. Individuals with schizophrenia had both superior and inferior strengths of connections between cortical regions compared with those of healthy controls. We observed regional abnormalities of the MS network in individuals with schizophrenia regarding lower centrality values of the pars opercularis, superior frontal, and superior temporal areas. Specific nodal network measures of the right pars opercularis and left superior temporal areas were associated with illness duration in individuals with schizophrenia. We identified regional abnormalities of the MS network in schizophrenia with the left superior temporal area possibly being a key region in topological organization and cortical connections.

[MR Imaging Features of Pediatric Bone Marrow]. / 소아 골수의 MR 영상 소견.

MRI plays a crucial role in bone marrow (BM) assessment, and has very high sensitivity in diagnosing marrow disorders. However, for radiologists who may not frequently encounter pediatric imaging, distinguishing pathologic BM lesion from normal BM can be challenging. Conditions involving the BM in pediatric patients, such as leukemia and metastatic neuroblastoma, often manifest with diverse musculoskeletal symptoms and may be diagnosed using musculoskeletal MRI examinations. Accurate interpretation of pediatric MRI requires not only an understanding of the normal composition of BM but also an awareness of agerelated developmental changes in the marrow and familiarity with conditions that commonly involve pediatric BM. We aim to describe the composition of normal BM and outline the normal and abnormal MRI findings in pediatric BM. Additionally, we aim to present clinical cases of malignant BM disorders including leukemia, neuroblastoma metastasis, and other malignant BM disorders.

Superb Microvascular Imaging in Pediatric Focal Nodular Hyperplasia.

OBJECTIVE: To investigate superb microvascular imaging (SMI), a novel Doppler ultrasound technique that can visualize low-velocity microvascular flow, for assessing pediatric focal nodular hyperplasia (FNH). PATIENTS AND METHODS: Nine FNH lesions in 6 patients were enrolled. On SMI and color Doppler imaging (CDI), intralesional vascularity was assessed visually and categorized as typical spoke-wheel pattern (central vessel radiating from the center to the periphery), multifocal spoke-wheel pattern, and nonspecific pattern. We compared the vascular features of the lesions between SMI and CDI and evaluated vascular patterns according to lesion size. RESULTS: In terms of vascularity pattern, the typical spoke-wheel pattern of FNH was noted more frequently on SMI (67%) than on CDI (11%; P < 0.05). In addition, a multifocal spoke-wheel pattern was noted in all remaining lesions (33%) on SMI. On the contrary, a nonspecific vascular pattern was detected in the majority (78%) of CDI. Regarding the lesion size and vascularity on SMI, the typical spoke-wheel pattern was seen more frequently in the small FNH group than in the large FNH group. The intralesional vascular signal was detected more frequently on SMI (100%) than on CDI (89%). CONCLUSION: SMI is feasible in evaluating FNH in children and has a greater ability to demonstrate the spoke-wheel pattern than CDI.

[Malrotation and Midgut Volvulus in Children: Diagnostic Approach, Imaging Findings, and Pitfalls]. / 소아의 ìž¥íšŒì „ì´ìƒê³¼ ì¤‘ìž¥ì—¼ì „: ì§„ë‹¨ì  ì ‘ê·¼, 영상 소견 및 í•¨ì •ë“¤.

Malrotation and midgut volvulus are surgical emergencies that commonly occur within the first month of life. The classic symptom is acute bilious vomiting, while nonspecific symptoms such as recurrent abdominal pain may be present in older children. Malrotation can be associated with duodenal obstruction caused by an abnormal peritoneal fibrous band or congenital anomalies, such as an annular pancreas or a preduodenal portal vein. Volvulus can lead to bowel ischemia and a life-threatening condition, thus prompt and accurate diagnosis is crucial. Diagnosis can be made through upper gastrointestinal series, ultrasonography, and CT, with ultrasonography being preferred as a screening tool due to its rapid and accurate diagnosis, without radiation exposure, in children. This pictorial essay discusses the key imaging findings and diagnostic approaches for malrotation and midgut volvulus, as well as diagnostic pitfalls based on actual cases.

Multimodal-based machine learning approach to classify features of internet gaming disorder and alcohol use disorder: A sensor-level and source-level resting-state electroencephalography activity and neuropsychological study.

OBJECTIVES: Addictions have recently been classified as substance use disorder (SUD) and behavioral addiction (BA), but the concept of BA is still debatable. Therefore, it is necessary to conduct further neuroscientific research to understand the mechanisms of BA to the same extent as SUD. The present study used machine learning (ML) algorithms to investigate the neuropsychological and neurophysiological aspects of addictions in individuals with internet gaming disorder (IGD) and alcohol use disorder (AUD). METHODS: We developed three models for distinguishing individuals with IGD from those with AUD, individuals with IGD from healthy controls (HCs), and individuals with AUD from HCs using ML algorithms, including L1-norm support vector machine, random forest, and L1-norm logistic regression (LR). Three distinct feature sets were used for model training: a unimodal-electroencephalography (EEG) feature set combined with sensor- and source-level feature; a unimodal-neuropsychological feature (NF) set included sex, age, depression, anxiety, impulsivity, and general cognitive function, and a multimodal (EEG + NF) feature set. RESULTS: The LR model with the multimodal feature set used for the classification of IGD and AUD outperformed the other models (accuracy: 0.712). The important features selected by the model highlighted that the IGD group had differential delta and beta source connectivity between right intrahemispheric regions and distinct sensor-level EEG activities. Among the NFs, sex and age were the important features for good model performance. CONCLUSIONS: Using ML techniques, we demonstrated the neurophysiological and neuropsychological similarities and differences between IGD (a BA) and AUD (a SUD).

Preoperative imaging findings to predict 2-year native liver survival after the Kasai procedure in patients with biliary atresia.

OBJECTIVES: To investigate the feasibility of using preoperative imaging indices to predict 2-year native liver survival after the Kasai procedure in patients with biliary atresia (BA). MATERIALS AND METHODS: The retrospective review included 190 BA patients who underwent the Kasai procedure between 2000 and 2020, with preoperative US and/or MRI, excluding cases with less than 2-year follow-up period. Multivariable logistic regression analysis was performed to identify imaging indices to predict 2-year native liver survival. Kasai failure was defined as the need for liver transplantation or death within 2 years of the Kasai procedure. RESULTS: Of the 90 patients included, all had preoperative US, and 61 also had MRI. Kasai failure occurred in 52% (47/90). Preoperative US identified gallbladder length (OR 0.40, 95% CI 0.17-0.95, p = 0.039; cutoff 1.6 cm, AUC 67.66) and biliary cysts (OR 24.64, 95% CI 1.97-308.08, p = 0.013) as significant Kasai failure predictors, with a combined accuracy of 73% (60/82). For patients having both preoperative US and MRI, significant predictors were hepatic artery diameter (OR 6.75, 95% CI 1.31-34.88, p = 0.023; cutoff 2 mm, AUC 73.83) and biliary cysts (OR 23.89, 95% CI 1.43-398.82, p = 0.027) on US, and gallbladder length (OR 0.25, 95% CI 0.08-0.76, p = 0.014; cutoff 1.2 cm, AUC 74.72) and spleen size (OR 2.53, 95% CI 1.02-6.29, p = 0.045; cutoff 6.9 cm, AUC 73.72) on MRI, with a combined accuracy of 85% (52/61). CONCLUSION: Preoperative US and/or MRI enhance the 2-year native liver survival prediction in BA patients after the Kasai procedure. CLINICAL RELEVANCE STATEMENT: BA patients with hepatic artery diameter > 2 mm (US), gallbladder length < 1.6 cm (US) or < 1.2 cm (MRI), spleen size > 6.9 cm (MRI), and absence of biliary cysts (US/MRI) have a decreased likelihood of 2-year native liver survival. KEY POINTS: • Preoperative US and/or MRI can predict the probability of achieving 2-year native liver survival following the Kasai procedure. • Combining US and MRI improved the accuracy to 85% for predicting 2-year native liver survival in BA patients. • The hepatic artery diameter > 2 mm (US), gallbladder length < 1.6 cm (US) or < 1.2 cm (MRI), spleen size > 6.9 cm (MRI), and no biliary cysts (US/MRI) are significant predictors of Kasai failure in patients with biliary atresia.

Diffusion-Weighted MR Imaging of the Thymus in Children with Non-Thymic Neoplasms.

Purpose: To investigate the diffusion-weighted imaging (DWI) findings and apparent diffusion coefficient (ADC) value of the thymus in children under the age of 13 who have non-thymic neoplasms. Materials and Methods: From January 2021 to April 2023, a single-center retrospective study analyzed consecutive 191 thoracic MRI scans with DWI from 67 children (<13 years) with non-thymic neoplasms. The scans were categorized based on the presence of restricted diffusion on DWI. We analyzed the demographics, laboratory data, and MR findings of the thymus. Statistical differences were assessed using generalized estimating equations. Results: Forty-five percent (86/191) of the scans exhibited restricted diffusion in the thymus: multifocal (n = 65; 76%), focal (n = 19; 22%), and diffuse (n = 2; 2%) patterns. The restricted diffusion group demonstrated higher absolute lymphocyte counts, more prominent thymus sizes, and higher frequency of off-treatment status compared to the unrestricted diffusion group (p>0.05). The mean ADC value across all 191 scans was 1.80 × 10-3 mm2/s. No significant difference was observed in the ADC value related to restricted diffusion patterns, the MRI vendors, or the age at the time of the scan. Conclusions: Restricted diffusion was observed in 45% of the thymus in children with non-thymic neoplasms, with a mean ADC value of 1.80 × 10-3 mm2/s. Recognizing the DWI findings can prevent unnecessary invasive procedures, alleviating concerns for patients and families.

Clinical and Imaging Features of Cystic Fibrosis in Korean Children.

Cystic fibrosis (CF) is a fatal hereditary disorder that primarily affects Caucasians and is rare in Asian populations, including Koreans. Diagnosing CF is often challenging and delayed owing to its rarity and its overlapping features with non-CF diseases, ultimately affecting the patient prognosis. Radiologists can provide initial clues for clinically unsuspected cases and play a crucial role in establishing an early childhood diagnosis. This pictorial essay reviews the clinical and imaging features of genetically confirmed CF in Korean children and increases awareness of this rare disease, thereby facilitating early diagnosis.

Regional brain activity of resting-state fMRI and auditory oddball ERP with multimodal approach in individuals with internet gaming disorder.

Background and aims: Resting-state brain activity may be associated with the ability to perform tasks; however, a multimodal approach involving resting-state functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) has not been widely used to investigate addictive disorders. Methods: We explored resting-state fMRI and auditory oddball ERP values from 26 with internet gaming disorder (IGD) patients and 27 age- and intelligence quotient-matched healthy controls (HCs). To assess the characteristics of resting-state fMRI, we calculated regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional amplitude of low-frequency fluctuation (fALFF); we also calculated the P3 component of the ERPs. Results: Compared with HCs, the individuals with IGD exhibited significant decreases in ReHo and fALFF values in the left inferior occipital gyrus, increased ReHo and ALFF values in the right precuneus, increased ALFF in the left superior frontal gyrus, and lower P3 amplitudes in the midline centro-parietal area during the auditory ERP task. Furthermore, the regional activity of resting-state fMRI in the right inferior temporal gyrus and the occipital regions were positively correlated with the P3 amplitudes in IGD patients, whereas ReHo values of the left hippocampus and the right amygdala were negatively correlated with P3. Discussion and conclusions: Our results suggest that IGD patients have difficulty interacting effectively with cognitive function and sensory processing, although its interpretations need some cautions. The findings in this study will broaden the overall understanding of the neurobiological mechanisms that underlie IGD pathophysiology.

Facial Expressions Track Depressive Symptoms in Old Age.

Facial expressions play a crucial role in the diagnosis of mental illnesses characterized by mood changes. The Facial Action Coding System (FACS) is a comprehensive framework that systematically categorizes and captures even subtle changes in facial appearance, enabling the examination of emotional expressions. In this study, we investigated the association between facial expressions and depressive symptoms in a sample of 59 older adults without cognitive impairment. Utilizing the FACS and the Korean version of the Beck Depression Inventory-II, we analyzed both "posed" and "spontaneous" facial expressions across six basic emotions: happiness, sadness, fear, anger, surprise, and disgust. Through principal component analysis, we summarized 17 action units across these emotion conditions. Subsequently, multiple regression analyses were performed to identify specific facial expression features that explain depressive symptoms. Our findings revealed several distinct features of posed and spontaneous facial expressions. Specifically, among older adults with higher depressive symptoms, a posed face exhibited a downward and inward pull at the corner of the mouth, indicative of sadness. In contrast, a spontaneous face displayed raised and narrowed inner brows, which was associated with more severe depressive symptoms in older adults. These findings suggest that facial expressions can provide valuable insights into assessing depressive symptoms in older adults.

Oncolytic Virus Engineering and Utilizations: Cancer Immunotherapy Perspective.

Oncolytic viruses have positively impacted cancer immunotherapy over the past 20 years. Both natural and genetically modified viruses have shown promising results in treating various cancers. Various regulatory authorities worldwide have approved four commercial oncolytic viruses, and more are being developed to overcome this limitation and obtain better anti-tumor responses in clinical trials at various stages. Faster advancements in translating research into the commercialization of cancer immunotherapy and a comprehensive understanding of the modification strategies will widen the current knowledge of future technologies related to the development of oncolytic viruses. In this review, we discuss the strategies of virus engineering and the progress of clinical trials to achieve virotherapeutics.

Filter-Free, Harmless, and Single-Wavelength Far UV-C Germicidal Light for Reducing Airborne Pathogenic Viral Infection.

Germicidal lamps that primarily emit 254 nm ultraviolet (UV) radiation have been effectively utilized for surface sterilization, but they cannot be used on human skin and eyes due to their harmful and genotoxic activity. Recent reports have shown that far UV-C light (207-222 nm) can efficiently kill pathogens with potentially no harm to exposed human tissues. However, these methods still require additional filtering and/or further protective equipment. In this study, we demonstrate a filter-free, harmless, and single-wavelength far UV-C 207 nm germicidal light source that can be used to inactivate different respiratory viruses. It can be exploited as a safe and effective disinfection tool for various airborne viruses. We successfully developed a single-wavelength far UV-C source that produces an exact wavelength of 207 nm. We examined its safety on human skin and corneal cell lines, as well as its effects on inactivating different airborne viruses, such as coronavirus, adenovirus, and vaccinia virus. We expect that our far UV-C lamps can be safely and conveniently used to reduce COVID-19 infections and protect both our living spaces and hospitals from the threat of contamination by possible new or mutant viruses.

Imaging of Umbilical Venous Catheter-Related Hepatic Complications in Neonates.

An umbilical venous catheter (UVC) is commonly placed for central venous access in preterm or critically ill full-term neonates to provide total parenteral nutrition (TPN) and medication. However, UVCs can result in complications, including infection, portal vein thrombosis, and hepatic tissue injury. The inadvertent administration of hypertonic fluid through a malpositioned UVC can also cause hepatic parenchymal damage with mass-like fluid collection that simulates a tumorous condition during imaging. Ultrasonography and radiographic examinations play an essential role in detecting UVC-related complications. This pictorial essay aims to present the imaging findings of UVC-related hepatic complications in neonates.

Engineered Phage-Based Cancer Vaccines: Current Advances and Future Directions.

Bacteriophages have emerged as versatile tools in the field of bioengineering, with enormous potential in tissue engineering, vaccine development, and immunotherapy. The genetic makeup of phages can be harnessed for the development of novel DNA vaccines and antigen display systems, as they can provide a highly organized and repetitive presentation of antigens to immune cells. Bacteriophages have opened new possibilities for the targeting of specific molecular determinants of cancer cells. Phages can be used as anticancer agents and carriers of imaging molecules and therapeutics. In this review, we explored the role of bacteriophages and bacteriophage engineering in targeted cancer therapy. The question of how the engineered bacteriophages can interact with the biological and immunological systems is emphasized to comprehend the underlying mechanism of phage use in cancer immunotherapy. The effectiveness of phage display technology in identifying high-affinity ligands for substrates, such as cancer cells and tumor-associated molecules, and the emerging field of phage engineering and its potential in the development of effective cancer treatments are discussed. We also highlight phage usage in clinical trials as well as the related patents. This review provides a new insight into engineered phage-based cancer vaccines.

Resting-state heart rate variability, level of stress and resilience in internet gaming disorder and alcohol use disorder.

Stress and resilience are involved in the pathophysiology of addictive disorders, and heart rate variability (HRV) is an index of an individual's global capability to regulate psychological responses. In this study, we aimed to identify transdiagnostic and disorder-specific markers in people with addictive disorders by analyzing resting-state HRV and associations with the levels of stress and resilience. We compared relevant data between patients with internet gaming disorder (IGD) and/or alcohol use disorder (AUD) and healthy controls (HCs). In all, 163 adults aged 18-35 years (53 with IGD, 49 with AUD, 61 HCs) participated. The levels of stress and resilience were measured using the Psychosocial Wellbeing Index and the Connor-Davidson Resilience Scale, respectively. The HRV was obtained from each participant during a 5 min resting-state. The IGD and AUD patients exhibited increased levels of stress and decreased resilience compared to the HCs. Patients with either addictive disorder exhibited a lower standard deviation of the normal-to-normal beat interval (SDNN) index [SDNNi] compared to HCs even after adjusting for clinical variables such as depression, anxiety, and impulsivity. In multiple comparison tests among the three groups, the AUD group had lower HRV than HCs, but no differences were observed among the groups after adjusting for the clinical variables. The HRV indices were correlated with the levels of stress, resilience, and disease severity. In conclusion, IGD and AUD patients exhibit lower HRV as indicated by the SDNNi compared to HCs, revealing their vulnerability to stress as well as a common transdiagnostic marker of addiction.