Poly(ß-amino ester) polymer library with monomer variation for mRNA delivery.

Non-viral vectors for mRNA delivery primarily include lipid nanoparticles (LNPs) and polymers. While LNPs are known for their high mRNA delivery efficiency, they can induce excessive immune responses and cause off-target effects, potentially leading to side effects. In this study, we aimed to explore polymer-based mRNA delivery systems as a viable alternative to LNPs, focusing on their mRNA delivery efficiency and potential application in mRNA vaccines. We created a library of poly(ß-amino ester) (PBAE) polymers by combining various amine monomers and acrylate monomers. Through screening this polymer library, we identified specific polymer nanoparticles (PNPs) that demonstrated high mRNA expression efficiency, with sustained mRNA expression for up to two weeks. Furthermore, the PNPs showed mRNA expression only at the injection site and did not exhibit liver toxicity. Additionally, when assessing immune activation, the PNPs significantly induced T-cell immune activation and were effective in the plaque reduction neutralization test. These results suggest that polymer-based mRNA delivery systems not only hold potential for use in mRNA vaccines but also show promise for therapeutic applications.

Shock indices are associated with in-hospital mortality among patients with septic shock and normal left ventricular ejection fraction.

BACKGROUND: The understanding of shock indices in patients with septic shock is limited, and their values may vary depending on cardiac function. METHODS: This prospective cohort study was conducted across 20 university-affiliated hospitals (21 intensive care units [ICUs]). Adult patients (≥19 years) with septic shock admitted to the ICUs during a 29-month period were included. The shock index (SI), diastolic shock index (DSI), modified shock index (MSI), and age shock index (Age-SI) were calculated at sepsis recognition (time zero) and ICU admission. Left ventricular (LV) function was categorized as either normal LV ejection fraction (LVEF ≥ 50%) or decreased LVEF (<50%). RESULTS: Among the 1,194 patients with septic shock, 392 (32.8%) who underwent echocardiography within 24 h of time zero were included in the final analysis (normal LVEF: n = 246; decreased LVEF: n = 146). In patients with normal LVEF, only survivors demonstrated significant improvement in SI, DSI, MSI, and Age-SI values from time zero to ICU admission; however, no notable improvements were found in all patients with decreased LVEF. The completion of vasopressor or fluid bundle components was significantly associated with improved indices in patients with normal LVEF, but not in those with decreased LVEF. In multivariable analysis, each of the four indices at ICU admission was significantly associated with in-hospital mortality (P < 0.05) among patients with normal LVEF; however, discrimination power was better in the indices for patients with lower lactate levels (≤ 4.0 mmol/L), compared to those with higher lactate levels. CONCLUSIONS: The SI, DSI, MSI, and Age-SI at ICU admission were significantly associated with in-hospital mortality in patients with septic shock and normal LVEF, which was not found in those with decreased LVEF. Our study emphasizes the importance of interpreting shock indices in the context of LV function in septic shock.

Early Prediction of Mortality for Septic Patients Visiting Emergency Room Based on Explainable Machine Learning: A Real-World Multicenter Study.

BACKGROUND: Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department. METHODS: This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO2/FIO2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine). The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley's additive explanations (SHAP). RESULTS: Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756-0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626-0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results. CONCLUSION: Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.

Impact of sepsis on Eastern Cooperative Oncology Group performance status among fully ambulatory patients: a prospective nationwide multicenter cohort.

Background: Investigations of the impact of sepsis on the Eastern Cooperative Oncology Group performance status (ECOG PS) of fully ambulatory patients are scarce. Methods: This is a retrospective analysis of prospectively collected nationwide data on septic patients recruited from 19 hospitals of the Korean Sepsis Alliance between August 2019 and December 2020. Adult septic patients with good ECOG PS (i.e., 0 or 1) before sepsis were enrolled in this study. The change in ECOG PS and the prevalence of disability (ECOG PS ≥2) at hospital discharge were recorded. Results: Of the 4,145 septic patients, 1,735 (41.9%) patients who had ECOG PS of 0 or 1 before sepsis and eventually survived to discharge were selected. After treatment for sepsis, the ECOG PS deteriorated in 514 (29.6%) patients; 376 (21.7%) patients had poor ECOG PS (i.e., ≥2) at hospital discharge. The proportion of patients with poor ECOG PS at hospital discharge increased with increases in the initial sequential organ failure assessment (SOFA) score and lactate level. Furthermore, poor ECOG PS at hospital discharge was found in young patients (aged <65 years, 17.4%), those with no history of cancer (18.2%) or with low comorbidities [Charlson comorbidity index (CCI) ≤2; 13.6%], and those without septic shock (19.9%). In multivariable analysis, age, solid cancer, immunocompromised condition, SOFA score, mechanical ventilation, and use of inappropriate empirical antibiotics (odds ratio: 1.786; 95% confidence interval: 1.151-2.771) were significant risk factors for poor ECOG PS. Conclusions: One in five septic patients who were fully ambulatory before sepsis were not functionally independent at hospital discharge. Incomplete functional recovery was also seen in a substantial proportion of younger patients, those with low comorbidities, and those without septic shock. However, the adequacy of empirical antibiotics may improve the functional status in such patients.

Pancreatic serous cystic neoplasm mimicking intraductal papillary mucinous neoplasm: Two case reports and literature review.

RATIONALE: Serous cystic neoplasms (SCNs) are treated as benign lesions. It is widely known that SCN rarely have a connection with the main pancreatic duct (MPD), which helps differentiate them from other cystic lesions, such as intraductal papillary mucinous neoplasm (IPMN). However, very rare cases where the SCN appears connected to the MPD cause diagnostic confusion. PATIENT CONCERNS: We present 2 patients with SCN (1 male, 54, and 1 female, 42). Both patients were asymptomatic, without abnormal laboratory results. DIAGNOSIS: In both cases, abdominopelvic computed tomography and pancreatic magnetic resonance imaging scans revealed a multilobulated cystic lesion in communication with the MPD. Since the size of each patient's lesion was >3 cm and there was connectivity with the MPD, it was strongly suspected to be a branch duct-type IPMN with worrisome features rather than SCN and surgical intervention was considered. INTERVENTIONS: Both neoplasms were misdiagnosed as IPMN due to appearing connected with the MPD on radiologic imaging. Surgery was performed. OUTCOMES: A final diagnosis of microcystic serous cystadenoma of the pancreas without connectivity of MPD was confirmed in both patients. LESSONS: An unnecessary surgery was performed due to atypical radiologic features in which the pancreatic duct seems to be connected to the pancreatic cystic lesion on magnetic resonance imaging, leading to misdiagnosis of SCN as IPMN. Particular attention should be paid to interpretation of clinicoradiologic findings of pancreatic cystic lesions, especially to the decision of surgical intervention. Also, awareness of presence of the atypical radiologic features of SCN may broaden the knowledge base of radiologists. LESSONS: An unnecessary surgery was performed due to atypical radiologic features in which the pancreatic duct seems to be connected to the pancreatic cystic lesion on magnetic resonance imaging, leading to misdiagnosis of SCN as IPMN. Particular attention should be paid to interpretation of clinicoradiologic findings of pancreatic cystic lesions, especially to the decision of surgical intervention. Also, awareness of presence of the atypical radiologic features of SCN may broaden the knowledge base of radiologists.

HYPOTENSION AT THE TIME OF SEPSIS RECOGNITION IS NOT ASSOCIATED WITH INCREASED MORTALITY IN SEPSIS PATIENTS WITH NORMAL LACTATE LEVELS.

ABSTRACT: Background and Objective: Although sepsis is heterogeneous, data on sepsis patients with normal lactate levels are very limited. We explored whether hypotension at the time of sepsis recognition (i.e., time zero) was significant in terms of survival when lactate levels were normal in sepsis patients. Patients and Design: This was a prospective multicenter observational study conducted in 19 hospitals (20 intensive care units [ICUs]). Adult sepsis patients with normal lactate levels (≤2 mmol/L) admitted to ICUs were divided by the mean arterial pressure at time zero into hypotensive (<65 mm Hg) and nonhypotensive groups (≥65 mm Hg). Measurements and Results: Of 2,032 patients with sepsis (not septic shock), 617 with normal lactate levels were included in the analysis. The hypotensive group (n = 237) was characterized by higher rates of abdominal or urinary infections, and bacteremia, whereas the nonhypotensive group (n = 380) was characterized by higher rates of pulmonary infections and systemic inflammatory response. However, the Simplified Acute Physiology Score 3 and Sequential Organ Failure Assessment score (excluding the cardiovascular score) were not different between the groups. During sepsis resuscitation, the rates of antibiotic administration within 1, 3, and 6 h of time zero were higher in the hypotensive than nonhypotensive group ( P < 0.05 for all time points), and the amounts of pre-ICU fluids given were also higher in the hypotensive group. However, despite a higher rate of vasopressor use in the hypotensive group, ICU and in-hospital mortality rates were not different between the groups (12.7% vs. 13.9% [ P = 0.648] and 19.4% vs. 22.4% [ P = 0.382], respectively). In multivariable analysis, the use of appropriate antibiotics and early lactate measurement were significant risk factors for in-hospital mortality. Conclusions: In sepsis patients with normal lactate levels, neither hypotension nor vasopressor use adversely impacted the hospital outcome. Our results emphasize the importance of early interventions and appropriate use of antibiotics regardless of whether a patient is or is not hypotensive.

An explanatory model of quality of life in high-risk pregnant women in Korea: a structural equation model.

PURPOSE: This study aimed to develop and validate a structural model for the quality of life (QoL) among high-risk pregnant women, based on Roy's adaptation model. METHODS: This cross-sectional study collected data from 333 first-time mothers diagnosed with a high-risk pregnancy in two obstetrics and gynecology clinics in Cheonan, Korea, or participating in an online community, between October 20, 2021 and February 20, 2022. Structured questionnaires measured QoL, contextual stimuli (uncertainty), coping (adaptive or maladaptive), and adaptation mode (fatigue, state anxiety, antenatal depression, maternal identity, and marital adjustment). RESULTS: The mean age of the respondents was 35.29±3.72 years, ranging from 26 to 45 years. The most common high-risk pregnancy diagnosis was gestational diabetes (26.1%). followed by preterm labor (21.6%). QoL was higher than average (18.63±3.80). Above-moderate mean scores were obtained for all domains (psychological/baby, 19.03; socioeconomic, 19.00; relational/spouse-partner, 20.99; relational/family-friends, 19.18; and health and functioning, 16.18). The final model explained 51% of variance in QoL in high-risk pregnant women, with acceptable overall model fit. Adaptation mode (ß=-.81, p=.034) and maladaptive coping (ß=.46 p=.043) directly affected QoL, and uncertainty (ß=-. 21, p=.004), adaptive coping (ß=.36 p=.026), and maladaptive coping (ß=-.56 p=.023) indirectly affected QoL. CONCLUSION: It is essential to develop nursing interventions aimed at enhancing appropriate coping strategies to improve QoL in high-risk pregnant women. By reinforcing adaptive coping strategies and mitigating maladaptive coping, these interventions can contribute to better maternal and fetal outcomes and improve the overall well-being of high-risk pregnant women.

Immunostimulation of tumor microenvironment by targeting tumor-associated macrophages with hypoxia-responsive nanocomplex for enhanced anti-tumor therapy.

Tumor-associated macrophages (TAMs), which dampen the therapeutic efficacy of cancer immunotherapy, are the key players in the immunosuppressive tumor microenvironment (TME). Therefore, reprogramming TAMs into tumoricidal M1 macrophages possesses considerable potential as a novel immunotherapy. However, the low bioavailability of polarization agents and limited accumulation of TAMs restrict their anti-tumor efficacy. In this study, we developed a polymer-based hypoxia-responsive nanocomplex to target TAMs in hypoxia for enhanced cancer immunotherapy. We synthesized a hypoxia-cleavable polymer poly(ethylene glycol)-azo-poly(l-lysine) (PEG-azo-PLL) and formulated a nanocomplex by simple mixing PEG-azo-PLL and poly(I:C). By mimicking in vitro hypoxia conditions, PEG-azo-PLL/poly(I:C) complexes could transform the physicochemical properties to enhance the delivery efficiency of poly(I:C) to tumor hypoxia, where M2-like TAMs are accumulated. Furthermore, PEG-azo-PLL/poly(I:C) could successfully reduce the population of M2-like TAMs in hypoxic tumors and promoted infiltration of CD8+ T cells in vivo, resulting in the favorable conversion of immunosuppressive TME. Finally, PEG-azo-PLL/poly(I:C) could elicit a significant in vivo anti-tumor effect in B16F10-bearing mice in addition to a prolonged survival time, demonstrating that the hypoxia-responsive nanocomplex PEG-azo-PLL/poly(I:C) is a promising approach for TAM reprogramming immunotherapy for solid tumors.

The Impact of Antepartum Depression and Postpartum Depression on Exclusive Breastfeeding: A Systematic Review and Meta-Analysis.

The aim of this study was to systematically review the impact of antepartum depression on exclusive breastfeeding. A total of 15 studies were included in the review and 12 studies were used for the meta-analysis. The mean values of antepartum depression indicated that women who breastfed exclusively between 3 and 6 months had less antepartum depression symptoms (Mean Difference = -0.55, 95% CI = -0.76 to -0.35). The analysis also showed that the existence of antepartum depression was negatively related to continuing exclusive breastfeeding for longer than 3 months postpartum as well as for 8 weeks postpartum (OR = 0.48, 95% CI = 0.26-0.88 and OR = 0.83, 95% CI = 0.75-0.91, respectively). The cumulative evidence is conclusive that antepartum depressive symptoms are negatively associated with exclusive breastfeeding, particularly between 3 and 6 months postpartum. This review supports the necessity of screening and follow-up for depression throughout the perinatal period to promote exclusive breastfeeding for 6 months.

Failure of High-Flow Nasal Cannula Therapy in Pneumonia and Non-Pneumonia Sepsis Patients: A Prospective Cohort Study.

Despite the increasing use of high-flow nasal cannulas (HFNCs) to treat critically ill patients, data on their effectiveness for sepsis patients remains very limited. We studied a prospective cohort of sepsis patients from the Korean Sepsis Registry (18 intensive care units (ICUs)). Patients started on HFNC therapy for hypoxemia within the first three ICU days were enrolled. HFNC failure was defined as intubation or ICU death, and the primary outcome was early HFNC failure occurring within 72 h of HFNC initiation. Of 901 patients with sepsis admitted to the ICU, 206 who received HFNC therapy were finally included (117 with pneumonia vs. 89 with non-pneumonia sepsis; median age, 71.0 (63.0-78.0) years; PaO2/FiO2 ratio, 160.2 (107.9-228.2) mm Hg; septic shock, n = 81 (39.3%)). During HFNC therapy, 72 (35.0%) patients were intubated and 51 (24.8%) died. HFNC failure developed in 95 (46.1%) patients, and among them, early failure rate was 85.3% (81/95). On multivariate analysis, an immunocompromised state (odds ratio (OR) = 2.730), use of a combination of antibiotics (OR = 0.219), and the PaO2/FiO2 ratio (OR = 0.308) were significantly associated with early HFNC failure in pneumonia sepsis patients. However, in non-pneumonia sepsis patients, lactate levels (OR = 1.532) were significantly associated with early HFNC failure. In conclusion, a high proportion of sepsis patients experience HFNC failure, usually within 72 h after therapy initiation, which emphasizes the importance of close monitoring. Furthermore, unlike in pneumonia sepsis, organ failure (i.e., lactate) might serve as a prognostic marker in non-pneumonia sepsis (i.e., type IV respiratory failure).

Mesothelial cyst of the spleen mimicking a metastasis: a case report.

Mesothelial cyst of the spleen is a developmental disorder. Previous reports have elaborated on the radiological features of splenic mesothelial cysts as being unilocular with a smooth and well-defined margin. However, due to its rarity, it is unclear whether these characteristics are representative and specific for the diagnosis of mesothelial cysts. Herein, this case report presents an atypical case of splenic mesothelial cyst mimicking a malignant tumour, especially splenic metastasis in a 66-year-old woman with ascending colon cancer. Due to an overlapping imaging finding of hypodense splenic lesions, and considering the clinical history, a mesothelial cyst that developed as a multilocular hypodense mass from an ill-defined small nodule was inevitably misdiagnosed as metastasis. Although rare, it is important to consider the possibility of mesothelial cyst in a patient with multilocular hypodense lesions of the spleen.

Validation of the Korean version of the Perinatal Infant Care Social Support scale: a methodological study.

Purpose: The purpose of this study was to develop and test the validity and reliability of the Korean version of the Perinatal Infant Care Social Support (K-PICSS) for postpartum mothers. Methods: This study used a cross-sectional design. The K-PICSS was developed through forward-backward translation. Online survey data were collected from 284 Korean mothers with infants 1-2 months of age. The 19-item K-PICSS consists of functional and structural domains. The functional domain of social support measures infant care practices of postpartum mothers. Exploratory factor analysis (EFA) and known-group comparison were used to verify the construct validity of the K-PICSS. Social support and postpartum depression were also measured to test criterion validity. Psychometric testing was not applicable to the structural social support domain. Results: The average age of mothers was 32.76±3.34 years, and they had been married for 38.45±29.48 months. Construct validity was supported by the results of EFA, which confirmed a three-factor structure of the scale (informational support, supporting presence, and practical support). Significant correlations of the K-PICSS with social support (r=.71, p<.001) and depression (r=-.40, p<.001) were found. The K-PICSS showed reliable internal consistency, with Cronbach's α values of .90 overall and .82-.83 in the three subscales. The vast majority of respondents reported that their husband or their parents were their main sources of support for infant care. Conclusion: This study demonstrates that the K-PICSS has satisfactory construct validity and reliability to measure infant care social support in Korea.

Transformation of Colloidal Quantum Dot: From Intraband Transition to Localized Surface Plasmon Resonance.

An increase in the carrier density of semiconductor nanocrystals can gradually change the origin of the optical property from the excitonic transition to the localized surface plasmon resonances. Here, we present the evolution of the electronic transition of self-doped Ag2Se colloidal quantum dots, from the intraband transition to the localized surface plasmon resonances along with a splitting of the intraband transition (1Pe-1Se). The minimum fwhm of the split intraband transition is only 23.7 meV, which is exceptionally narrow compared to that of metal oxide nanocrystals showing LSPRs, inferring that the electron-electron scattering is significantly suppressed due to the smaller carrier density. The splitting of the intraband transition mainly results from the asymmetrical crystal structure of the tetragonal Ag2Se CQDs and becomes distinct when the nanocrystal changes its crystal structure from the cubic to tetragonal structure. Maximizing the discrete energy levels in the quantum dot along with mixing with plasmonic characters may provide opportunities to fully harness merits of both the quantum confinement effect and localized surface plasmon resonance characters.

Cesium Lead Bromide Quantum Dot Light-Emitting Field-Effect Transistors.

Solution-processable perovskite quantum dots are considered as promising optical materials for light-emitting optoelectronics. Light-emitting field-effect transistors (LEFETs) that can be operated under a relatively lower potential with a high energy conversion efficiency are yet to be realized with perovskite quantum dots. Here, we present the CsPbBr3 quantum dot-based LEFET. Surprisingly, unipolar transport characteristics with strong electroluminescence were observed at the interface of the CsPbBr3 QD-LEFET along with an exceptionally wide recombination zone of 80 µm, an order of magnitude larger than that of organic/polymer LEFETs. Based on the systematic analysis for the electroluminescence of the CsPbBr3 NC-LEFET, we revealed that the increased diffusion length determined by the majority carrier mobility and the lifetime well explains the remarkably wide recombination zone. Furthermore, it was found that the energy-level matching and transport geometry of the heterostructure also determine the charge distribution and recombination, substantially affecting the performance of the CsPbBr3 QD LEFET.

Multifunctional Self-Doped Nanocrystal Thin-Film Transistor Sensors.

Self-doping in nanocrystals allows accessing higher quantum states. The electrons occupying the lowest energy state of the conduction band form a metastable state that is very sensitive to the electrostatic potential of the surface. Here, we demonstrate that the high charge sensitivity of the self-doped HgSe colloidal quantum dot solid can be used for sensing three different targets with different phases through self-doped HgSe nanocrystal/ZnO thin-film transistors: the environmental gases (CO2 gas, NO gas, and H2S gas); mid-IR photon; and biothiol (l-cysteine) molecules. The self-doped quantum dot solid detects the targets through different mechanisms. The physisorption of the CO2 gas and the NO gas molecules, and the mid-IR photodetection show reversible processes, whereas the chemisorption of l-cysteine biothiol and H2S gas molecules shows irreversible processes. Considering the quenching of mid-IR intraband photoluminescence of the HgSe colloidal quantum dot solid by the vibrational mode of the CO2 gas molecule, sensing the CO2 gas could be involved in the electronic-to-vibrational energy transfer. The target molecules are quantitatively analyzed, and the limits of detection for CO2 and l-cysteine are 250 ppm and 10 nM, respectively, which are comparable to the performance of commercial detectors.