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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. [ABSTRACT FROM AUTHOR]

In this study, we reviewed smog chamber systems and methodologies used in secondary organic aerosol (SOA) formation studies. Many important chambers across the world have been reviewed, including 18 American, 24 European, and 8 Asian chambers. The characteristics of the chambers (location, reactor size, wall materials, and light sources), measurement systems (popular equipment and working principles), and methodologies (SOA yield calculation and wall-loss correction) are summarized. This review discussed key experimental parameters such as surface-to-volume ratio (S/V), temperature, relative humidity, light intensity, and wall effect that influence the results of the experiment, and how the methodologies have evolved for more accurate simulation of atmospheric processes. In addition, this review identifies the sources of uncertainties in finding SOA yields that are originated from experimental systems and methodologies used in previous studies. The intensity of the installed artificial lights (photolysis rate of NO2 varied from 0.1/min to 0.40/min), SOA density assumption (varied from 1 g/cm3 to 1.45 g/cm3), wall-loss management, and background contaminants were identified as important sources of uncertainty. The methodologies developed in previous studies to minimize those uncertainties are also discussed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The late-stage functionalization of a biomimetic foldamer such as a peptoid is a useful tool to achieve structural diversity. Herein, a facile method for the synthesis of triazole- or tetrazole-containing peptoids using post-synthetic modifications has been reported. On a resin-bound peptoid with a chloroalkyl side chain(s), substitution with nucleophiles (azide or cyanide) and the subsequent [3 + 2]-cycloaddition reaction were optimized. Peptoids with azide, triazole, and tetrazole functional groups could be readily synthesized and could potentially be utilized further for orthogonal bioconjugation or metal recognition. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Since a display panel comprises multiple layered components, defects may occur within different layers through manufacturing processes. Traditional visual inspection systems with a 2D camera cannot identify the occurrence location among layers. Several 3D imaging technologies, such as CT, TSOM, and MRI, suffer from slow performance and a large form factor. In this work, we propose a novel visual inspection method to detect defects on a display panel using light-field 3D imaging. Without powering the target display panel, we first acquire the high-resolution depth information of defects located inside the transparent layers. We then convert the depth information to the object coordinate system to estimate the physical locations of defects. We automatically classify the types of defects and their layer locations along the depth axis in multiple transparent layers of the display panel. Lastly, our experimental results validate that our method can successfully detect and classify various display defects. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Tetrahydrocyclopenta[d]imidazole-based JNK3 inhibitor was designed and synthesized. • Subnanomolar IC 50 s on JNK3 were observed in these analogs with isoform selectivity. • Compound 22b exhibited superb potency of 0.379 nM, outperforming any JNK3 inhibitor. • In silico study indicated the scaffold have 4 important H-bonds in the active site. • JNK3 inhibitors showed neuroprotective effect against Aβ induced cellular apoptosis. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • N -(5-amido-2-methylphenyl)-5-methylisoxazole-3-carboxamide derivatives were designed as CSF1R inhibitors. • Nanomolar inhibitory effect against CSF1R were observed in the compounds 7d and 9a havng c-Kit inhibitory effects. • Compounds 7d and 9a exhibited excellent kinase selectivity and cellular effect. • Compounds 7d and 9a exhibited strong BBB permeability, good MS and PS, making them potential anti-neuroinflammation agents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-1 H -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. [Display omitted] • 2-Aryl-1-pyrimidinyl-1 H -imidazole-yl acetonitrile were designed as JNK3 inhibitors. • Compound 15d exhibited superb potency of 1 nM and excellent isoform selectivity. • Compound 15g exhibited potency of 4 nM and good oral pharmacokinetic profile. • JNK3 inhibitors showed neuroprotective effect against Aβ induced cellular apoptosis. • Administration of 15d / 15g improved cognitive function of AD mice in havioral test. [ABSTRACT FROM AUTHOR]