Optical nanomaterial-based detection of biomarkers in liquid biopsy.

Liquid biopsy, which is a minimally invasive procedure as an alternative to tissue biopsy, has been introduced as a new diagnostic/prognostic measure. By screening disease-related markers from the blood or other biofluids, it promises early diagnosis, timely prognostication, and effective treatment of the diseases. However, there will be a long way until its realization due to its conceptual and practical challenges. The biomarkers detected by liquid biopsy, such as circulating tumor cell (CTC) and circulating tumor DNA (ctDNA), are extraordinarily rare and often obscured by an abundance of normal cellular components, necessitating ultra-sensitive and accurate detection methods for the advancement of liquid biopsy techniques. Optical biosensors based on nanomaterials open an important opportunity in liquid biopsy because of their enhanced sensing performance with simple and practical properties. In this review article, we summarized recent innovations in optical nanomaterials to demonstrate the sensitive detection of protein, peptide, ctDNA, miRNA, exosome, and CTCs. Each study prepares the optical nanomaterials with a tailored design to enhance the sensing performance and to meet the requirements of each biomarker. The unique optical characteristics of metallic nanoparticles (NPs), quantum dots, upconversion NPs, silica NPs, polymeric NPs, and carbon nanomaterials are exploited for sensitive detection mechanisms. These recent advances in liquid biopsy using optical nanomaterials give us an opportunity to overcome challenging issues and provide a resource for understanding the unknown characteristics of the biomarkers as well as the mechanism of the disease.

Effect of resuscitative endovascular balloon occlusion of the aorta in nontraumatic out-of-hospital cardiac arrest: a multinational, multicenter, randomized, controlled trial.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a significant public health issue worldwide and is associated with low survival rates and poor neurological outcomes. The generation of optimal coronary perfusion pressure (CPP) via high-quality chest compressions is a key factor in enhancing survival rates. However, it is often challenging to provide adequate CPP in real-world cardiopulmonary resuscitation (CPR) scenarios. Based on animal studies and human trials on improving CPP in patients with nontraumatic OHCA, resuscitative endovascular balloon occlusion of the aorta (REBOA) is a promising technique in these cases. This study aims to investigate the benefits of REBOA adjunct to CPR compared with conventional CPR for the clinical management of nontraumatic OHCA. METHODS: This is a parallel-group, randomized, controlled, multinational trial that will be conducted at two urban academic tertiary hospitals in Korea and Taiwan. Patients aged 20-80 years presenting with witnessed OHCA will be enrolled in this study. Eligible participants must fulfill the inclusion criteria, and written informed consent should be collected from their legal representatives. Patients will be randomly assigned to the intervention (REBOA-CPR) or control (conventional CPR) group. The intervention group will receive REBOA and standard advanced cardiovascular life support (ACLS). Meanwhile, the control group will receive ACLS based on the 2020 American Heart Association guidelines. The primary outcome is the return of spontaneous circulation (ROSC). The secondary outcomes include sustained ROSC, survival to admission, survival to discharge, neurological outcome, and hemodynamic changes. DISCUSSION: Our upcoming trial can provide essential evidence regarding the efficacy of REBOA, a mechanical method for enhancing CPP, in OHCA resuscitation. Our study aims to determine whether REBOA can improve treatment strategies for patients with nontraumatic OHCA based on clinical outcomes, thereby potentially providing valuable insights and guiding further advancements in this critical public health area. TRIAL REGISTRATION: ClinicalTrials.gov NCT06031623. Registered on September 9, 2023.

The Magnitude of Change in Serum Phosphate Concentration Is Associated with Mortality in Patients with Severe Trauma.

PURPOSE: Previous studies have suggested that serum phosphate concentration is a prognostic factor in critically ill patients. However, the association between changes in serum phosphate levels and prognosis of patients with trauma remains unclear. MATERIALS AND METHODS: This study included patients with severe trauma who were treated at the emergency department. Delta phosphate (Δ phosphate) was defined as the difference between serum phosphate concentrations measured at baseline and after 24 hours from the initial measurement. Patients were divided into five groups according to their Δ phosphate levels: group I (Δ phosphate <-2 mg/dL), group II (Δ phosphate -2 to -0.5 mg/dL), group III (Δ phosphate -0.5 to 0.5 mg/dL), group IV (Δ phosphate 0.5 to 2 mg/dL), and group V (Δ phosphate ≥2 mg/dL). RESULTS: Overall, 1905 patients with severe trauma were included in the analysis. The 30-day mortality was the lowest in group III and tended to increase in groups with a larger Δ phosphate in both the positive and negative directions (group I: 13.7%, group II: 6.8%, group III: 4.6%, group IV: 6.6%, and group V: 26.8%). In multivariable analysis with group III as the reference group, the odds ratios (ORs) of mortality were statistically significant in group IV [OR, 1.92; 95% confidence interval (CI), 1.05-3.56] and group V (OR, 5.28; 95% CI, 2.47-11.24). CONCLUSION: An increase in serum phosphate concentrations 24 hours after the initial measurement could be considered as an independent prognostic factor in patients with severe trauma.

The first record of leucism in the Rhabdophis tigrinus (Boie, 1826) (Squamata, Colubridae) in South Korea.

Leucism, in which pigmentation is lost over part or the entire body of an animal, has a range of possible genetic causes. Here, we report leucism in an individual tiger keelback (Rhabdophis tigrinus) found on Jeung Island, Shinan-gun, Jeollanam-do, South Korea, during a survey of the distribution of reptiles in the area. The individual was observed sunbathing in the bushes next to a pond. This individual exhibited ecdysis, thus it considered that have normal feeding activity. Our report represents the first observation of leucism in R. tigrinus, and thus, further analysis is needed of this phenotype to more clearly understand its impact on the species and its natural history.

Enhancement mechanism of quantum yield in core/shell/shell quantum dots of ZnS-AgIn5S8/ZnIn2S4/ZnS.

To achieve a high quantum yield (QY) of nanomaterials suitable for optical applications, we improved the optical properties of AgIn5S8 (AIS) quantum dots (QDs) by employing an alloyed-core/inner-shell/outer-shell (ZAIS/ZIS/ZnS) structure. We also investigated the mechanism of optical transitions to clarify the improvement of QYs. In AIS, the low-energy absorption near the band edge region is attributed to the weakly allowed band gap transition, which gains oscillator strength through state intermixing and electron-phonon coupling. The main photoluminescence is also ascribed to the weakly allowed band gap transition with characteristics of self-trapped excitonic emission. With alloying/shelling processes, the weakly allowed transition is enhanced by the evolution of the electronic structures in the alloyed core, which improves the band gap emission. In shelled structures, the nonradiative process is reduced by the reconstructed lattice and passivated surface, ultimately leading to a high QY of 85% in ZAIS/ZIS/ZnS. These findings provide new insights into the optical transitions of AIS because they challenge previous conclusions. In addition, our work elucidates the mechanism behind the enhancement of QY accomplished through alloying/shelling processes, providing strategies to optimize nontoxic QDs for various applications using a green chemistry approach.

Integrated proteogenomic characterization of glioblastoma evolution.

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.

Clinical and molecular predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia: A retrospective cohort study.

BACKGROUND/PURPOSE: To investigate the virulence profiles and identify clinical and microbiological predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii (A. baumannii) bacteremia. METHODS: This retrospective cohort study enrolled adult patients with carbapenem-resistant A. baumannii (CRAB). Multivariate logistic regression was used to identify the predictors of 30-day mortality. All isolates were subjected to real-time polymerase chain reaction for virulence factors and genotyped using multilocus sequence typing. RESULTS: Among the 153 patients with CRAB bacteremia, 66 % received appropriate definitive antibiotic therapy. The in-hospital and 30-day mortality rates were 58.3 and 23.5 %, respectively. Ultimately, we enrolled 125 patients with CRAB bacteremia in the analysis, excluding early mortality cases. All CRAB isolates carried blaOXA-23 and blaOXA-51. The clinical strains belonged to 10 sequence types (STs), and the major genotypes were ST191, ST195, ST451, and ST784. The distribution of virulence factors included surface adhesion (Ata, 84.8 %; ChoP, 7.2 %), biofilm formation (OmpA, 76.8 %), killing of host cells (AbeD, 99.2 %), toxins (LipA, 99.2 %), and conjugation (BfmR, 90.4 %). In multivariate logistic regression analysis, hemodialysis due to acute kidney injury and moderate to severe thrombocytopenia were significant risk factors associated with 30-day mortality. However, microbiological factors were not significant predictors. CONCLUSIONS: Clinical factors such as hemodialysis due to acute renal injury and moderate to severe thrombocytopenia have a greater influence on mortality in CRAB bacteremia compared with microbiological factors.

Population-level call properties of endangered Dryophytes suweonensissensu lato (Anura: Amphibia) in South Korea.

Calling is one of the unique amphibian characteristics that facilitates social communication and shows individuality; however, it also makes them vulnerable to predators. Researchers use amphibian call properties to study their population status, ecology, and behavior. This research scope has recently broadened to species identification and taxonomy. Dryophytes flaviventris has been separated from the endangered anuran species, D. suweonensis, based on small variations in genetic, morphometric, and temporal call properties observed in South Korea. The Chilgap Mountain (CM) was considered as the potential geographic barrier for the speciation. However, it initiated taxonomic debates as CM has been hardly used and is considered a potential barrier for other species. The calls of populations from both sides are also apparently similar. Thus, to verify the differences in call properties among populations of D. suweonensis sensu lato (s.l.; both of the species), we sampled and analyzed call data from five localities covering its distribution range, including the southern (S) and northern (N) parts of CM. We found significant differences in many call properties among populations; however, no specific pattern was observed. Some geographically close populations, such as Iksan (S), Wanju (S), and Gunsan (S), had significant differences, whereas many distant populations, such as Pyeongtaek (N) and Wanju (S), had no significant differences. Considering the goal of this study was only to observe the call properties, we cautiously conclude that the differences are at the population level rather than the species level. Our study indicates the necessity of further investigation into the specific status of D. flaviventris using robust integrated taxonomic approaches, including genetic and morphological parameters from a broader array of localities.

Impact of an Emergency Department Isolation Policy for Patients With Suspected COVID-19 on Door-to-Electrocardiography Time and Clinical Outcomes in Patients With Acute Myocardial Infarction.

BACKGROUND: Rapid electrocardiography diagnosis within 10 minutes of presentation is critical for acute myocardial infarction (AMI) patients in the emergency department (ED). However, the coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the emergency care system. Screening for COVID-19 symptoms and implementing isolation policies in EDs may delay the door-to-electrocardiography (DTE) time. METHODS: We conducted a cross-sectional study of 1,458 AMI patients who presented to a single ED in South Korea from January 2019 to December 2021. We used multivariate logistic regression analysis to assess the impact of COVID-19 pandemic and ED isolation policies on DTE time and clinical outcomes. RESULTS: We found that the mean DTE time increased significantly from 5.5 to 11.9 minutes (P < 0.01) in ST segment elevation myocardial infarction (STEMI) patients and 22.3 to 26.7 minutes (P < 0.01) in non-ST segment elevation myocardial infarction (NSTEMI) patients. Isolated patients had a longer mean DTE time compared to non-isolated patients in both STEMI (9.2 vs. 24.4 minutes) and NSTEMI (22.4 vs. 61.7 minutes) groups (P < 0.01). The adjusted odds ratio (aOR) for the effect of COVID-19 duration on DTE ≥ 10 minutes was 1.93 (95% confidence interval [CI], 1.51-2.47), and the aOR for isolation status was 5.62 (95% CI, 3.54-8.93) in all patients. We did not find a significant association between in-hospital mortality and the duration of COVID-19 (aOR, 0.9; 95% CI, 0.52-1.56) or isolation status (aOR, 1.62; 95% CI, 0.71-3.68). CONCLUSION: Our study showed that ED screening or isolation policies in response to the COVID-19 pandemic could lead to delays in DTE time. Timely evaluation and treatment of emergency patients during pandemics are essential to prevent potential delays that may impact their clinical outcomes.

Molecular and virulence characteristics of carbapenem-resistant Acinetobacter baumannii isolates: a prospective cohort study.

This study aimed to characterize the molecular features and virulence profiles of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. Clinical CRAB isolates were obtained from blood cultures of adult patients with CRAB bacteremia, collected between July 2015 and July 2021 at a Korean hospital. Real-time polymerase chain reaction was used to detect 13 virulence genes, genotyping was conducted via multilocus sequence typing (MLST), and a Tenebrio molitor infection model was selected for survival analysis. Herein, 170 patients, from whom CRAB isolates were collected, showed the in-hospital mortality rate of 57.6%. All 170 clinical CRAB isolates harbored blaOXA-23 and blaOXA-51. MLST genotyping identified 11 CRAB sequence types (STs), of which ST191 was predominant (25.7%). Virulence genes were distributed as follows: basD, 58.9%; espA, 15.9%; bap, 92.4%; and ompA, 77.1%. In the T. molitor model, ST195 showed a significantly higher mortality rate (73.3% vs. 66.7%, p = 0.015) than the other groups. Our findings provide insights into the microbiological features of CRAB blood isolates associated with high mortality. We suggest a potential framework for using a T. molitor infection model to characterize CRAB virulence. Further research is warranted to elucidate the mechanisms by which virulence improves clinical outcomes.

Delayed arrival of advanced life support adversely affects the neurological outcome in a multi-tier emergency response system.

AIM: Prehospital management of out-of-hospital cardiac arrest (OHCA) is based on basic life support, with the addition of advanced life support (ALS) if possible. This study aimed to investigate the effect of delayed arrival of ALS on neurological outcomes of patients with OHCA at hospital discharge. METHODS: This was a retrospective study of a registry of patients with OHCA. A multi-tier emergency response system was established in the study area. ALS was initiated when the second-arrival team arrived at the scene. A restricted cubic spline curve was used to investigate the relationship between the response time interval of the second-arrival team and neurological outcomes at hospital discharge. Multivariable logistic regression analysis was performed to assess the independent association between the response time interval of the second-arrival team and neurological outcomes of patients at hospital discharge. RESULTS: A total of 3186 adult OHCA patients who received ALS at the scene were included in the final analysis. A restricted cubic spline curve showed that a long response time interval of the second-arrival team was correlated with a high likelihood of poor neurological outcomes. Meanwhile, multivariable logistic regression analysis showed that a long response time interval of the second-arrival team was independently associated with poor neurological outcomes (odds ratio, 1.10; 95% confidence interval, 1.03-1.17). CONCLUSION: In a multi-tiered prehospital emergency response system, the delayed arrival of ALS was associated with poor neurological outcomes at hospital discharge.

Recent Trends in Lateral Flow Immunoassays with Optical Nanoparticles.

Rapid, accurate, and convenient diagnosis is essential for effective disease management. Various detection methods, such as enzyme-linked immunosorbent assay, have been extensively used, with lateral flow immunoassay (LFIA) recently emerging as a major diagnostic tool. Nanoparticles (NPs) with characteristic optical properties are used as probes for LFIA, and researchers have presented various types of optical NPs with modified optical properties. Herein, we review the literature on LFIA with optical NPs for the detection of specific targets in the context of diagnostics.

Lower limb muscle matters in patients with hypoxic brain injury following out-of-hospital cardiac arrest.

BACKGROUND: There are conflicting results regarding the association between body mass index and the prognosis of cardiac arrest patients. We investigated the association of the composition and distribution of muscle and fat with neurologic outcomes at hospital discharge in successfully resuscitated out-of-hospital cardiac arrest (OHCA) patients. METHODS: This prospective, single-centre, observational study involved adult OHCA patients, conducted between April 2019 and June 2021. The ratio of total skeletal muscle, upper limb muscle, lower limb muscle, and total fat to body weight was measured using InBody S10, a bioimpedance analyser, after achieving the return of spontaneous circulation. Restricted cubic spline curves with four knots were used to examine the relationship between total skeletal muscle, upper limb muscle, and lower limb muscle relative to total body weight and neurologic outcome at discharge. Multivariable logistic regression analysis was performed to assess an independent association. RESULTS: A total of 66 patients were enrolled in the study. The proportion of total muscle and lower limb muscle positively correlated with the possibility of having a good neurologic outcome. The proportion of lower limb muscle showed an independent association in the multivariable analysis (adjusted odds ratio, 2.29; 95% confidence interval, 1.06-13.98), and its optimal cut-off value calculated through receiver operating characteristic curve analysis was 23.1%, which can predict a good neurological outcome. CONCLUSIONS: A higher proportion of lower limb muscle to body weight was independently associated with the probability of having a good neurologic outcome in OHCA patients.

Usability testing of a blind intubation device for intubation novices: a randomized crossover simulation study.

OBJECTIVE: A new blind intubation device (BID) has been developed for endotracheal intubation. This study aimed to test the usability of the BID in comparison to direct laryngoscopy (DL) and video laryngoscopy (VL) with inexperienced healthcare providers for endotracheal intubation. METHODS: This was a randomized crossover simulation study. Participants who had conducted fewer than five live intubation sessions were included in the study. The manikin simulation was conducted using a Laerdal trainer airway manikin. Participants performed intubation using all three devices, DL, VL, and BID. The primary outcome was intubation success rate in the first pass the secondary outcome was intubation time to first ventilation, and the tertiary outcome was dental injury. RESULTS: A total of 45 healthcare workers who were novices in intubation participated in this study, including 13 physicians (interns), 14 emergency medical technicians, and 18 nurses. The intubation success rates in the first pass with BID, DL, and VL were 93.3%, 91.1%, and 97.8%, respectively (P=0.53). The intubation times to first ventilation with BID, DL, and VL were 13.15±6.16, 19.07±7.71, and 17.31±6.57 seconds, respectively (P<0.01). The proportions of dental injuries associated with BID, DL, and VL were 0% for physicians; 28.6%, 14.3%, and 0%, respectively for emergency medical technicians; and 27.8%, 11.1%, and 16.7%, respectively for nurses. CONCLUSION: We performed a pilot study to test the usability of the new BID. There was no significant difference in intubation success rate in the first pass among BID, DL, and VL. The intubation time to first ventilation was shorter with the BID compared to DL and VL.

Passive monitoring by smart toilets for precision health.

Smart toilets are a key tool for enabling precision health monitoring in the home, but such passive monitoring has ethical considerations.

Confirmation of the local establishment of alien invasive turtle, Pseudemys peninsularis, in South Korea, using eggshell DNA.

Alien invasive species are posing conservation challenges worldwide. Pet trade, one of the many ways, is worsening the situation. Especially, pet turtles have been released into nature due to their longer life span and peoples' religious and traditional beliefs. In addition, unwanted and undesired pets are also released. While information on the successful local establishment and subsequent dispersal into new habitats is required to designate an invasive and ecosystem-disturbing species, alien freshwater turtle nests have always been hard to find and identify in nature. Because one should identify nests by the eggs, which do not always guide properly, as adults abandon the sites quickly. We thought the recent advancement in DNA technology may help improve the situation. We studied Pseudemys peninsularis, one of the most traded freshwater turtle pet species, which has already been reported from a wide range of wild areas in South Korea. Yet, it is not designated as ecosystem-disturbing species due to a lack of adequate information on their local reproduction and establishment. We conducted surveys and found two nests in Jeonpyeongje Neighborhood Park, Maewol-dong, Seo-gu, Gwangju. We developed the methodology for extracting DNA from the eggshells and successfully identified the nests by phylogenetic analysis and verified through egg characteristics and morphological features of artificially hatched juveniles. This was the first successful initiative to extract DNA from freshwater turtle eggshells. We believe it will help future researchers identify the alien invasive turtle nests and develop their control and management policies. In addition, our study also included comparative descriptions and schematic diagrams of the eggs of eight freshwater turtles, including a native and three ecosystem-disturbing species, from South Korea. We urged an immediate designation of P. peninsularis as an ecosystem-disturbing species considering its local establishment, distribution range, and potential negative impact on native ecosystems.

Synthesis and Applications of Optical Materials.

As optical materials have shown outstanding physical and chemical characteristics in the bio, medical, electronics, energy and related fields of studies, the potential benefits of using these materials have been widely recognized [...].

Hydrogel-based thermosensor using peptide nucleic acid and PEGylated graphene oxide.

Developing a ready-to-use miniaturized thermosensor is a great challenge due to its individual use on a large scale for daily business such as food industry and healthcare. Herein, a polyethylene glycol (PEG)-modified graphene oxide (GO)-based hydrogel thermosensor was established with a fluorescent dye-labeled peptide nucleic acid (F-PNA). The size-tunable hydrogel with high water content and sufficient solidity allowed free movement of the oligonucleotides through the pores and improved usability for handling the sensor. In the PEG-GO hydrogel, the DNA/F-PNA duplex could be denatured by increasing the temperature, followed by selective PNA capture on the PEG-GO. Using this principle, the PEG-GO hydrogel exhibited a change in the fluorescence signal of F-PNA in a temperature-dependent manner, allowing real-time visualization of temperature on a large scale. The temperature detection range of this system can be adjusted by designing the PNA strands based on the melting temperature of the DNAzyme/PNA duplex. Its sensing specificity and detection range could be increased and broadened by observing multi-color detection using PNA probes labeled with different fluorescent dyes of different lengths in a single hydrogel. In addition, the hydrogel platform is easy to store for long time periods via dehydration and can be restored with the addition of water, allowing easy transport, storage, and use of the thermosensor in everyday life.

Efficient Analysis of Small Molecules via Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (LDI-TOF MS) Using Gold Nanoshells with Nanogaps.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a commonly used technique for analyzing large biomolecules. However, the utilization of organic matrices limits the small-molecule analysis because of the interferences in the low-mass region and the reproducibility issues. To overcome these limitations, a surface-assisted laser desorption/ionization (SALDI), which utilizes nanostructured metallic surfaces, has been developed. Herein, a novel approach for SALDI-MS was proposed using silica@gold core-shell hybrid materials with a nanogap-rich shell (SiO2@Au NGS), which is an emerging material due to its excellent heat-generating capabilities. The gold shell thickness was controlled by adjusting the concentration of gold precursor for the growth of gold nanoparticles. SALDI-MS measurements were performed on a layer formed by drop-casting a mixture of SiO2@Au NGS and analytes. At the optimized process, the gold shell thickness was observed to be 17.2 nm, which showed the highest absorbance. Based on the enhanced SALDI capability, SiO2@Au NGS was utilized to detect various small molecules, including amino acids, sugars, and flavonoids, and the ionization softness was confirmed with a survival yield upon fragmentation. The limits of detection, reproducibility, and salt tolerance of SiO2@Au NGS demonstrate its potential as an effective and reliable SALDI material for small-molecule analyses.