Search

Introduction: The calcaneus is the most commonly fractured tarsal bone. Diagnosis is often challenging due to subtle radiographic changes and requires timely identification to prevent complications, including subtalar arthritis, neurovascular injury, malunion, osteomyelitis, and compartment syndrome. Treatment varies based on fracture type, with non-surgical methods for non-displaced stress fractures and surgical interventions for displaced or intra-articular fractures., Methods: This study utilized the Wisdom in Diagnostic Imaging Simulation (WIDI SIM) platform, an emergency imaging simulation designed to assess radiology resident preparedness for independent call. During an 8-hour simulation, residents were tested on 65 cases across various imaging modalities of varying complexity, including normal studies. A single, unique case of calcaneal fracture was included within the simulation in four separate years of testing. Cases were assessed using a standardized grading rubric by subspecialty radiology faculty, with errors subsequently classified by type., Results: A total of 1279 residents were tested in five separate years on the findings of calcaneal fractures of 5 different patients. Analysis revealed a consistent pattern of missed diagnoses across all training years, primarily attributed to observational errors. There was limited improvement with training progression as all training years exhibited similar average performance levels., Conclusions: Calcaneal fractures pose a diagnostic challenge due to their frequent subtle radiographic findings, especially in stress fractures. Simulation-based evaluations using WIDI SIM highlighted challenges in radiology residents' proficiency in diagnosing calcaneal fractures. Addressing these challenges through targeted education and exposure to diverse cases is essential to improve diagnostic accuracy and reduce complications with calcaneal fractures., (© 2024. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Deep learning has become the de facto method for medical image segmentation, with 3D segmentation models excelling in capturing complex 3D structures and 2D models offering high computational efficiency. However, segmenting 2.5D images, characterized by high in-plane resolution but lower through-plane resolution, presents significant challenges. While applying 2D models to individual slices of a 2.5D image is feasible, it fails to capture the spatial relationships between slices. On the other hand, 3D models face challenges such as resolution inconsistencies in 2.5D images, along with computational complexity and susceptibility to overfitting when trained with limited data. In this context, 2.5D models, which capture inter-slice correlations using only 2D neural networks, emerge as a promising solution due to their reduced computational demand and simplicity in implementation. In this paper, we introduce CSA-Net, a flexible 2.5D segmentation model capable of processing 2.5D images with an arbitrary number of slices. CSA-Net features an innovative Cross-Slice Attention (CSA) module that effectively captures 3D spatial information by learning long-range dependencies between the center slice (for segmentation) and its neighboring slices. Moreover, CSA-Net utilizes the self-attention mechanism to learn correlations among pixels within the center slice. We evaluated CSA-Net on three 2.5D segmentation tasks: (1) multi-class brain MR image segmentation, (2) binary prostate MR image segmentation, and (3) multi-class prostate MR image segmentation. CSA-Net outperformed leading 2D, 2.5D, and 3D segmentation methods across all three tasks, achieving average Dice coefficients and HD95 values of 0.897 and 1.40 mm for the brain dataset, 0.921 and 1.06 mm for the prostate dataset, and 0.659 and 2.70 mm for the ProstateX dataset, demonstrating its efficacy and superiority. Our code is publicly available at: https://github.com/mirthAI/CSA-Net., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Suppurative retropharyngeal lymphadenitis is a retropharyngeal space infection almost exclusively seen in the young (4-8 years old) pediatric population. It can be misdiagnosed as a retropharyngeal abscess, leading to unnecessary invasive treatment procedures. This retrospective study aims to assess radiology residents' ability to independently identify CT imaging findings and make a definitive diagnosis of suppurative retropharyngeal lymphadenitis in a simulated call environment., Materials and Methods: The Wisdom in Diagnostic Imaging Emergent/Critical Care Radiology Simulation (WIDI SIM) is a computer-aided emergency imaging simulation proven to be a reliable method for assessing resident preparedness for independent radiology call. The simulation included 65 cases across various imaging modalities of varying complexity, including normal studies, with one case specifically targeting suppurative retropharyngeal adenitis identification. Residents' free text responses were manually scored by faculty members using a standardized grading rubric, with errors subsequently classified by type., Results: A total of 543 radiology residents were tested in three separate years on the imaging findings of suppurative retropharyngeal lymphadenitis using the Wisdom in Diagnostic Imaging simulation web-based testing platform. Suppurative retropharyngeal lymphadenitis was consistently underdiagnosed by radiology residents being tested for call readiness irrespective of the numbers of years in training. On average, only 3.5% of radiology residents were able to correctly identify suppurative retropharyngeal lymphadenitis on a contrast-enhanced computed tomography (CT)., Conclusions: Our findings underscore a potential gap in radiology residency training related to the accurate identification of suppurative retropharyngeal lymphadenitis, highlighting the potential need for enhanced educational efforts in this area., (© 2024. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

This study explores the potential of CSF-1R inhibitors as therapeutic agents for neurodegenerative diseases. CSF-1R, a receptor tyrosine kinase primarily expressed in macrophage lineages, plays a pivotal role in regulating various cellular processes. Recent research highlights the significance of CSF-1R inhibition in mitigating neuroinflammation, particularly in Alzheimer's disease, where microglial overactivation contributes to neurodegeneration. The research reveals a series of N-(5-amido-2-methylphenyl)-5-methylisoxazole-3-carboxamide CSF-1R inhibitors, where compounds 7d, 7e, and 9a exhibit outstanding inhibitory activities and selectivity, with IC 50 values of 33, 31, and 64 nM, respectively. These most promising compounds in this series were profiled for cellular potency and subjected to in vitro pharmacokinetic profiling. These inhibitors exhibit minimal cytotoxicity, even at higher concentrations, and possess promising blood-brain barrier permeability, making them potential candidates for central nervous system diseases. The investigation into the in vitro ADME properties, including plasma and microsomal stability, reveals that these CSF-1R inhibitors maintain their structural integrity and plasma concentration. This resilience positions them for further development as therapeutic agents for neurodegenerative diseases., Competing Interests: Declaration of Competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Jung-Mi Hah reports financial support was provided by National Research Foundation., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Preterm infants bypass the crucial in utero period of brain development and are at increased risk of malnutrition. We aimed to determine if their nutritional status is associated with brain tissue volumes at term equivalent age (TEA), applying recently published malnutrition guidelines for preterm infants. We performed a single center retrospective chart review of 198 infants < 30 weeks' gestation between 2018 and 2021. We primarily analyzed the relationship between the manually obtained neonatal MR-based brain tissue volumes with the maximum weight and length z-score. Significant positive linear associations between brain tissue volumes at TEA and weight and length z-scores were found ( p < 0.05). Recommended nutrient intake for preterm infants is not routinely achieved despite efforts to optimize nutrition. Neonatal MR-based brain tissue volumes of preterm infants could serve as objective, quantitative and reproducible surrogate parameters of early brain development. Nutrition is a modifiable factor affecting neurodevelopment and these results could perhaps be used as reference data for future timely nutritional interventions to promote optimal brain volume.

In this study, we investigated the physicochemical and antioxidative properties of the traditional Korean confectionery, Yanggaeng, when various amounts of tempeh powder (TP) were added. We replaced a portion of the white bean paste in Yanggaeng with TP at percentages of 0% (CON), 2% (TP2), 4% (TP4), and 6% (TP6) by total weight. The proximate composition results showed that TP6 exhibited the highest crude ash and crude protein contents, but its moisture content and carbohydrate content were the lowest compared to the CON. Tempeh addition altered the colorimetric properties by increasing the L* value, b* value, and browning index; however, tempeh addition did not alter the a* value. The results also showed that tempeh addition gradually decreased the pH of Yanggaeng. The Brix value was the highest in TP2; in TP4 and TP6, the Brix value gradually decreased, and these formulations exhibited lower Brix values than the CON. Furthermore, tempeh addition gradually induced antioxidative capacities, as evidenced by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities. The results of this study demonstrate that the addition of tempeh to Yanggaeng alters its physicochemical properties and antioxidative capacity., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (© 2023 The Korean Society of Food Science and Nutrition.)

In this study, an impedance biosensor capable of real-time monitoring of the growth and drug reactions using NIH/3T3 cells was fabricated through a semiconductor process. With the fabricated impedance biosensor, the cell growth and drug reaction states are monitored in real-time, showing the validness of the developed biosensor. By using the developed impedance biosensor, we have investigated the capacitance contribution of NIH/3T3 cells existing on electrodes and between electrodes. To compare the capacitance value contributions of the cells on and between electrodes, wide- and narrow-gap electrode patterns are manufactured with 3.7 and 0.3 mm electrode gap spacings, respectively. From the detailed analysis, the capacitance contributions of NIH/3T3 cells existing on electrodes are estimated around less than 20 percent compared to the cells existing between electrodes. In other words, a minimized electrode area with maximized electrode spacing is the promising impedance biosensor design guide for accurate cell capacitance measurements.

Background: The timing-related deficits in individuals with attention deficit hyperactivity disorder (ADHD) contribute to the symptom-related difficulties and cognitive impairments. Current assessment and training measurement only target specific aspects of the timing ability, highlighting the need for more advanced tools to address timing deficits in ADHD. The aim of this study is to develop and validate a rhythm-based assessment and training (RAT) program, which intends to provide a comprehensive understanding of and enhancement to the time-related abilities of children with ADHD, thereby demonstrating its clinical efficacy., Methods: We will use randomized crossover trials in this study, with participants being randomly assigned to either start with the RAT and then proceed to cognitive training or start with cognitive training and then proceed to the RAT. Both groups will undergo pre- and post- evaluations. The evaluation will be administered immediately before and after the 4-week training period using diagnostic questionnaires, cognitive evaluation tools, and resting electroencephalography (EEG) measurements. Notably, EEG measurements will be conducted concurrently with the RAT evaluations., Discussion: This study develops and evaluates the feasibility and effectiveness of a RAT while using EEG measurements to elucidate the underlying therapeutic mechanism of auditory rhythm at varying levels of complexity. The study will investigate the potential of RAT as a supplementary or alternative approach for managing ADHD. The multifaceted data collected will yield valuable insights to customize training agendas based on individual developmental stages and prognoses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shin, Lee, Kang, Kim and Jeong.)

JNK3 is a key factor driving the pathophysiology of neuronal apoptosis. Since demonstrating the therapeutic potential of JNK3 inhibitors in Alzheimer's disease, we aimed to broaden their chemical diversity for drug development. In continuation with our previous research, a series of compounds with the tetrahydrocyclopenta[d]imidazole scaffold as a core moiety was developed as JNK3 inhibitors based on in silico modeling analysis. The biochemical kinase assay results revealed that the JNK3 inhibitory effects and isoform selectivity of the compounds developed in this study were significantly higher than that of previously developed inhibitors. In particular, the IC 50 values of compounds 18c, 19c, 22b, and 26c, which exhibited excelled isoform selectivity, against JNK3 were 0.716, 0.564, 0.379, and 0.779 nM, respectively, which were more potent than those of any known JNK3 inhibitors. Additionally, compounds 18c, 18c, 22b, and 22c effectively protected the neuronal cells against amyloid beta-induced apoptosis. Docking studies indicated that the tetrahydrocyclopenta[d]imidazole scaffold retained all the optimal interactions. Meanwhile, BBB PAMPA and ADME prediction suggested that the tested compounds had a favorable BBB permeability and pharmacokinetic profile. Therefore, the tetrahydrocyclopenta[d]imidazole scaffold is a promising candidate for developing JNK3 inhibitors. In particular, compound 22b is a potential starting point for the preclinical optimization of novel JNK3 inhibitors., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jung-Mi Hah reports financial support was provided by National Research Foundation., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Despite innumerable efforts to develop effective therapeutics, it is difficult to achieve breakthrough treatments for Alzheimer's disease (AD), and the main reason is probably the absence of a clear target. Here, we reveal c-Jun N-terminal kinase 3 (JNK3), a protein kinase explicitly expressed in the brain and involved in neuronal apoptosis, with a view toward providing effective treatment for AD. For many years, we have worked on JNK3 inhibitors and have discovered 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile-based JNK3 inhibitors with superb potency (IC 50  < 1.0 nM) and excellent selectivity over other protein kinases including isoforms JNK1 (>300 fold) and JNK2 (∼10 fold). Based on in vitro biological activity and DMPK properties, the lead compounds were selected for further in vivo studies. We confirmed that repeat administration of JNK3 inhibitors improved cognitive memory in APP/PS1 and the 3xTg mouse model. Overall, our results show that JNK3 could be a potential target protein for AD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jung-Mi Hah reports financial support was provided by National Research Foundation., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Fms-like tyrosine kinase 3 (FLT3) has been verified as a therapeutic target for acute myeloid leukaemia (AML). In this study, we report a series of 2-(1 H -indazol-6-yl)-1 H -benzo[d]imidazol-5-yl benzamide and phenyl urea derivatives as potent FLT3 inhibitors based on the structural optimisation of previous FLT3 inhibitors. Derivatives were synthesised as benzamide 8a - k , 8n - z , and phenyl urea 8l - m , with various substituents. The most potent inhibitor, 8r , demonstrated strong inhibitory activity against FLT3 and FLT3 mutants with a nanomolar IC 50 and high selectivity profiles over 42 protein kinases. In addition, these type II FLT3 inhibitors were more potent against FLT3 mutants correlated with drug resistance. Overall, we provide a theoretical basis for the structural optimisation of novel benzimidazole analogues to develop strong inhibitors against FLT3 mutants for AML therapeutics.

Background: The present study aimed to develop a rat model for mechanical allodynia after traumatic brain injury (TBI) and to investigate the expression of brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid (CSF) using this model., Methods: A total of 180 rats were randomly allocated into three groups: a control group (group C), a sham-operated group (group S), and a controlled cortical impact induced TBI group (group T), 60 in each group. Von Frey test was performed to evaluate mechanical withdrawal thresholds. An enzyme-linked immunosorbent assay was performed to quantify BDNF level in CSF., Results: The 50% withdrawal thresholds of group T were lower than those of group C and group S at all measuring points except for the preoperative period (P = 0.026, <0.001, and <0.001 for POD1, POD7, and POD14, respectively). The BDNF level of group T was higher than those of group C and group S at POD1 (P = 0.005)., Conclusion: Upregulation of the BDNF expression in CSF was observed in rats who developed mechanical allodynia on the day after TBI. Based on our findings, to elucidate the relationship between TBI-induced neuropathic pain and BDNF expression in CSF, further research should be carried out through a multifaceted approach to a broad spectrum of pain behavior models., Competing Interests: Prof. Dr. Wangseok Do reports grants from National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT), during the conduct of the study. Dr Soeun Jeon reports grants from National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT), during the conduct of the study. Dr Chang-Min You reports grants from National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT), during the conduct of the study. Dr Dahyun Kang reports grants from National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT), during the conduct of the study. Dr Jiyoon Lee reports grants from Pusan National University Hospital, grants from Korean government, during the conduct of the study. The authors report no conflicts of interest in this work., (© 2022 Do et al.)

Background: An airway-associated fire in an operating room can have devastating consequences for patients. Breathing circuit warmers (BCWs) are widely used to provide heated and humidified anesthetic gases and eventually prevent hypothermia during general anesthesia. Herein, we describe a case of a BCW-related airway fire., Case Presentation: In this case, an electrical short within a BCW wire caused a fire inside the circuit. Simultaneously, the fire was extinguished, ventilation was stopped, and the endotracheal tube was disconnected from the BCW. The patient was exposed to the fire for less than 10 s, resulting in burns to the trachea and bronchi. Immediately after airway burn, bronchoscopy showed no edema or narrowing except for soot in the trachea and both main bronchus. After the inhalation burn event, prophylactic antibiotics, bronchodilator, mucolytics nebulizer, and corticosteroid nebulizer were started. On bronchoscopy 3 days after the inhalation burn, mucosal erythematous edema was observed and the inflammatory reaction worsened. The inflammatory reaction showed aggravation for up to 2 weeks, and then gradually recovered, and the epithelium and mucous membrane of the upper respiratory tract returned to normal after 4 weeks. Eventually, the patient recovered without long-term complications and was successfully discharged., Conclusions: This is the first report of a fire caused by BCW. We wanted to share our experience of how we responded to an airway-related fire in an OR and treated the patient. It cannot be overemphasized that the electrical medical appliance associated with the airways are fatal to the patient in the event of a fire, so caution should always be exercised., (© 2021. The Author(s).)

Capacitive biosensors are manufactured on glass slides using the semiconductor process to monitor cell growth and cell-drug interactions in real time. Capacitance signals are continuously monitored for each 10 min interval during a 48 h period, with the variations of frequency from 1 kHz to 1 MHz. The capacitance values showed a gradual increase with the increase in NIH 3T3 cell numbers. After 48 h of growth, 6.67 μg/mL puromycin is injected for the monitoring of the cell-drug interaction. The capacitance values rapidly increased during a period of about 10 h, reflecting the rapid increase in the cell numbers. In this study, we monitored the state of cells and the cell-drug interactions using the developed capacitive biosensor. Additionally, we monitored the state of cell behavior using a JuLi TM Br&FL microscope. The monitoring of cell state by means of a capacitive biosensor is more sensitive than confluence measuring using a JuLi TM Br&FL microscope image. The developed capacitive biosensor could be applied in a wide range of bio-medical areas; for example, non-destructive real-time cell growth and cell-drug interaction monitoring.

Siderophore-mimicking macrocyclic peptoids were synthesized. Peptoid 3 with intramolecular hydrogen bonds showed an optimally arranged primary coordination sphere leading to a stable catecholate-iron complex. The tris(catecholato) structure of 3-Fe(iii) was determined with UV-vis, fluorescence, and EPR spectroscopies and DFT calculations. The iron binding affinity was comparable to that of deferoxamine, with enhanced stability upon air exposure.

The modulation of conformational flexibility in antimicrobial peptides (AMPs) has been investigated as a strategy to improve their efficacy against bacterial pathogens while reducing their toxicity. Here, we synthesized a library of helicity-modulated antimicrobial peptoids by the position-specific incorporation of helix-inducing monomers. The peptoids displayed minimal variations in hydrophobicity, which permitted the specific assessment of the effect of conformational differences on antimicrobial activity and selectivity. Among the moderately helical peptoids, the most dramatic increase in selectivity was observed in peptoid 17 , providing more than a 20-fold increase compared to fully helical peptoid 1 . Peptoid 17 had potent broad-spectrum antimicrobial activity that included clinically isolated multi-drug-resistant pathogens. Compared to pexiganan AMP, 17 showed superior metabolic stability, which could potentially reduce the dosage needed, alleviating toxicity. Dye-uptake assays and high-resolution imaging revealed that the antimicrobial activity of 17 was, as with many AMPs, mainly due to membrane disruption. However, the high selectivity of 17 reflected its unique conformational characteristics, with differential interactions between bacterial and erythrocyte membranes. Our results suggest a way to distinguish different membrane compositions solely by helicity modulation, thereby improving the selectivity toward bacterial cells with the maintenance of potent and broad-spectrum activity.

Peptoids are peptidomimetic polymers that are resistant to proteolysis and less prone to immune responses; thus, they can provide a practical alternative to peptides. Among the various therapeutic applications that have been explored, cationic amphipathic peptoids have demonstrated broad-spectrum antibacterial activity, including activity towards drug-resistant bacterial strains. While their potency and activity spectrum can be manipulated by sequence variations, bacterial selectivity and systemic toxicity need to be improved for further clinical development. To this aim, we incorporated various hydrophobic or cationic residues to improve the selectivity of the previously developed antibacterial peptoid 1. The analogs with hydrophobic residues demonstrated non-specific cytotoxicity, while those with an additional cationic residue showed improved selectivity and comparable antibacterial activity. Specifically, compared to 1, peptoid 7 showed much lower hemolysis and cytotoxicity, while maintaining the antibacterial activity. Therefore, we believe that peptoid 7 has the potential to serve as a promising alternative to current antimicrobial therapies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways. Recent studies demonstrated that PD-L1 expression is significantly correlated to the mutation status of EGFR, and activation of EGFR signaling can also induce the expression of PD-L1. However, the real linker between PD-L1 and EGFR signaling remains to be revealed. Our previous study revealed that the Hippo pathway effector YAP confers EGFR-TKI resistance in lung adenocarcinoma, and inhibition of YAP restores sensitivity to EGFR-TKIs. Thus, we examined whether PD-L1 is relevant, in terms of conferring EGFR-TKI resistance and whether YAP directly regulates the expression of PD-L1 in this context. First, we compared the expression levels of PD-L1 and YAP between EGFR-TKI-resistant PC9 cells and the parental PC9 adenocarcinoma cells. The expression levels of both YAP and PD-L1 were markedly higher in the EGFR-TKI-resistant cells compared to the parental cells, suggesting differential expression pattern between two cell types. YAP knockdown significantly decreased the expression of PD-L1 in the EGFR-TKI-resistant cells, while YAP overexpression increased the expression of PD-L1 in the parental PC9 cells. Then, our results revealed that YAP regulates the transcription of PD-L1, and the YAP/TEAD complex binds to the PD-L1 promoter. Surprisingly, knockdown of PD-L1 was sufficient to decrease cell proliferation and wound healing in the EGFR-TKI-resistant PC9 cells. These data suggest a PD1-independent oncogenic function of PD-L1. The Hippo effector YAP plays a crucial role in linking the PD-L1 and EGFR-TKI resistance by directly regulating the expression of PD-L1 in lung cancer. Targeting PD-L1 directly or via YAP could provide an effective therapeutic strategy for EGFR-TKI-resistant lung adenocarcinoma., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of Interest: None.