G protein ß subunits regulate Cav3.3 T-type channel activity and current kinetics via interaction with the Cav3.3 C-terminus.

Ca2+ influx through Cav3.3 T-type channel plays crucial roles in neuronal excitability and is subject to regulation by various signaling molecules. However, our understanding of the partners of Cav3.3 and the related regulatory pathways remains largely limited. To address this quest, we employed the rat Cav3.3 C-terminus as bait in yeast-two-hybrid screenings of a cDNA library, identifying rat Gß2 as an interaction partner. Subsequent assays revealed that the interaction of Gß2 subunit was specific to the Cav3.3 C-terminus. Through systematic dissection of the C-terminus, we pinpointed a 22 amino acid sequence (amino acids 1789-1810) as the Gß2 interaction site. Coexpression studies of rat Cav3.3 with various Gßγ compositions were conducted in HEK-293 cells. Patch clamp recordings revealed that coexpression of Gß2γ2 reduced Cav3.3 current density and accelerated inactivation kinetics. Interestingly, the effects were not unique to Gß2γ2, but were mimicked by Gß2 alone as well as other Gßγ dimers, with similar potencies. Deletion of the Gß2 interaction site abolished the effects of Gß2γ2. Importantly, these Gß2 effects were reproduced in human Cav3.3. Overall, our findings provide evidence that Gß(γ) complexes inhibit Cav3.3 channel activity and accelerate the inactivation kinetics through the Gß interaction with the Cav3.3 C-terminus.

Haplosporidium nelsoni and Perkinsus marinus occurrence in waters of Great Bay Estuary, New Hampshire.

In Great Bay Estuary, New Hampshire, USA, Haplosporidium nelsoni and Perkinsus marinus are 2 active pathogens of the eastern oyster Crassostrea virginica (Gmelin), that cause MSX (multinucleated sphere with unknown affinity 'X') and dermo mortalities, respectively. Whereas studies have quantified infection intensities in oyster populations and determined whether these parasites exist in certain planktonic organisms, no studies thus far have examined both infectious agents simultaneously in water associated with areas that do and do not have oyster populations. As in other estuaries, both organisms are present in estuarine waters throughout the Bay, especially during June through November, when oysters are most active. Waters associated with oyster habitats had higher, more variable DNA concentrations from these pathogenic organisms than waters at a non-oyster site. This finding allows for enhanced understanding of disease-causing organisms in New England estuaries, where oyster restoration is a priority.

The effects of music therapy on labor pain, childbirth experience, and self-esteem during epidural labor analgesia in primiparas: a non-randomized experimental study.

PURPOSE: This non-randomized study was performed to evaluate the effects of music therapy on labor pain, the childbirth experience, and self-esteem in women during vaginal delivery. METHODS: In total, 136 primiparous women over 37 weeks of gestation receiving epidural analgesia during vaginal delivery were recruited via convenience sampling. To minimize diffusion effects, data from the control group (n=71) were collected first (April 2020 to March 2021), followed by data from the music group (n=65; April 2021 to May 2022). Participants in the music group listened to classical music during labor, while the control group was offered usual care (no music). Labor pain was measured using a numeric rating scale (NRS), and self-esteem and childbirth experience were collected using self-report questionnaires. Data were analyzed using the independent t-test, chi-square test and Cronbach's α coefficients. RESULTS: The overall pain level (NRS) at baseline was 0 in both groups. Mothers in the music therapy group had lower levels of latent pain (t=1.95, p=.005), active pain (t=3.69, p<.001) and transition-phase pain (t=7.07, p<.001) than the control group. A significant difference was observed between the two groups, and the music therapy group expressed more positive perceptions of the childbirth experience (t=-1.36, p=.018). For self-esteem, the experimental group's score was slightly higher, but without a statistically significant difference from the control group. CONCLUSION: Using music therapy during labor decreased labor pain and improved the childbirth experience. Music therapy can be clinically recommended as a non-pharmacological, safe, and easy method for nursing care in labor. Clinical trail number: KCT008561.

Mass Spectrometry and Pharmacological Approaches to Measuring Cooption and Reciprocal Activation of Receptor Tyrosine Kinases.

Receptor tyrosine kinases (RTKs) can show extensive crosstalk, directly and indirectly. Elucidating RTK crosstalk remains an important goal in the clinical combination of anti-cancer therapies. Here, we present mass spectrometry and pharmacological approaches showing the hepatocyte growth factor receptor (MET)-promoting tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) and other membrane receptors in MET-amplified H1993 NSCLC cells. Conversely, in H292 wt-EGFR NSCLC cells, EGFR promotes the tyrosine phosphorylation of MET. Reciprocal regulation of the EGFR and insulin receptor (IR) was observed in the GEO CRC cells, where inhibition of the EGFR drives tyrosine phosphorylation of the insulin receptor. Similarly, in platelet-derived growth factor receptor (PDGFR)-amplified H1703 NSCLC cells, inhibition of the EGFR promotes the tyrosine phosphorylation of the PDGFR. These RTK interactions are used to illustrate basic principles applicable to other RTK signaling networks. More specifically, we focus on two types of RTK interaction: (1) co-option of one RTK by another and (2) reciprocal activation of one receptor following the inhibition of a distinct receptor.

Understanding Early COPD.

Whereas COPD is currently defined as the presence of spirometric obstruction, the pathologic changes in individuals at risk including chronic mucus hypersecretion and emphysema have been recognized for centuries. At the same time, we have struggled to define criteria that would help us identify patients at an early stage, prior to the development of pulmonary function abnormality. The concept of GOLD 0 was introduced in the hopes that symptoms would help to identify those at greatest risk for progression. While symptoms are a risk factor, in particular chronic bronchitis, the term was abandoned as the majority of individuals at risk who progress to COPD do not have symptoms. Since then, the related terms pre-COPD and early COPD have been introduced. They are similar in that the term pre-COPD identifies individuals based on symptoms, physiologic, or radiographic abnormality that do not meet criteria for COPD but are clearly at risk. The term early COPD extends that concept further, focusing on individuals who have early physiologic or radiographic abnormality but at the same time are young, thereby excluding those with late mild disease who may be less likely to progress. Whereas individuals with early COPD are now being recruited for observational studies, we are still challenged with determining the best way to identify patients at risk who should undergo additional testing as well as developing specific therapies for patients with early-stage disease.

Comparison of chitosan and gelatin-based films and application to antimicrobial coatings enriched with grapefruit seed extract for cherry tomato preservation.

Bio-based single, composite, and bilayer edible films were developed based on chitosan and gelatin, including grapefruit seed extract (GSE) as an antimicrobial agent. The physicochemical and antimicrobial properties of films were analyzed, and it was found that compounding and laminating two polymers could enhance their physicochemical properties. The composite film was strong, endurable, and flexible compared with the single ones. In addition, the composite and bilayer films had lower water vapor permeability than the single ones. Edible films and coatings with GSE presented a greater bactericidal effect than the inactive ones. In addition, the hardness, weight, and color changes of the coated cherry tomatoes during 7-day storage did not differ, whereas a bacterial reduction against Salmonella Typhimurium was revealed. Taken together, composite and bilayer films with CH and GL and enriched with GSE were developed for food packaging applications, and it showed improved mechanical, water barrier, and antimicrobial properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01254-9.

Corticosteroid outcome may be dependent of duration of use in severe COVID-19.

BACKGROUND/AIMS: For patients hospitalized with coronavirus disease 2019 (COVID-19) who require supplemental oxygen, the evidence of the optimal duration of corticosteroid is limited. This study aims to identify whether long-term use of corticosteroids is associated with decreased mortality. METHODS: Between February 10, 2020 and October 31, 2021, we analyzed consecutive hospitalized patients with COVID-19 with severe hypoxemia. The patients were divided into short-term (≤ 14 days) and long-term (> 14 days) corticosteroid users. The primary outcome was 60-day mortality. We performed propensity score (PS) analysis to mitigate the effect of confounders and conducted Kaplan-Meier curve analysis. RESULTS: There were 141 (52%) short-term users and 130 (48%) long-term corticosteroid users. The median age was 68 years and the median PaO2/FiO2 at admission was 158. Of the patients, 40.6% required high-flow nasal cannula, 48.3% required mechanical ventilation, and 11.1% required extracorporeal membrane oxygenation. The overall 60-day mortality rate was 23.2%, and that of patients with hospital-acquired pneumonia (HAP) was 22.9%. The Kaplan-Meier curve for 60- day survival in the PS-matched cohort showed that corticosteroid for > 14 days was associated with decreased mortality (p = 0.0033). There were no significant differences in bacteremia and HAP between the groups. An adjusted odds ratio for the risk of 60-day mortality in short-term users was 5.53 (95% confidence interval, 1.90-18.26; p = 0.003). CONCLUSION: For patients with severe COVID-19, long-term use of corticosteroids was associated with decreased mortality, with no increase in nosocomial complications. Corticosteroid use for > 14 days can benefit patients with severe COVID-19.

Development of a Soil Moisture Prediction Model Based on Recurrent Neural Network Long Short-Term Memory (RNN-LSTM) in Soybean Cultivation.

Due to climate change, soil moisture may increase, and outflows could become more frequent, which will have a considerable impact on crop growth. Crops are affected by soil moisture; thus, soil moisture prediction is necessary for irrigating at an appropriate time according to weather changes. Therefore, the aim of this study is to develop a future soil moisture (SM) prediction model to determine whether to conduct irrigation according to changes in soil moisture due to weather conditions. Sensors were used to measure soil moisture and soil temperature at a depth of 10 cm, 20 cm, and 30 cm from the topsoil. The combination of optimal variables was investigated using soil moisture and soil temperature at depths between 10 cm and 30 cm and weather data as input variables. The recurrent neural network long short-term memory (RNN-LSTM) models for predicting SM was developed using time series data. The loss and the coefficient of determination (R2) values were used as indicators for evaluating the model performance and two verification datasets were used to test various conditions. The best model performance for 10 cm depth was an R2 of 0.999, a loss of 0.022, and a validation loss of 0.105, and the best results for 20 cm and 30 cm depths were an R2 of 0.999, a loss of 0.016, and a validation loss of 0.098 and an R2 of 0.956, a loss of 0.057, and a validation loss of 2.883, respectively. The RNN-LSTM model was used to confirm the SM predictability in soybean arable land and could be applied to supply the appropriate moisture needed for crop growth. The results of this study show that a soil moisture prediction model based on time-series weather data can help determine the appropriate amount of irrigation required for crop cultivation.

Development of an implantable collamer lens sizing model: a retrospective study using ANTERION swept-source optical coherence tomography and a literature review.

BACKGROUND: Optimal sizing for phakic intraocular lens (EVO-ICL with KS-AquaPort) implantation plays an important role in preventing postoperative complications. We aimed to formulate optimal lens sizing using ocular biometric parameters measured with a Heidelberg anterior segment optical coherence tomography (AS-OCT) device. METHODS: We retrospectively analyzed 892 eyes of 471 healthy subjects treated with an intraocular collamer lens (ICL) and assigned them to either the development (80%) or validation (20%) set. We built vault prediction models using the development set via classic linear regression methods as well as partial least squares and least absolute shrinkage and selection operator (LASSO) regression techniques. We evaluated prediction abilities based on the Bayesian information criterion (BIC) to select the best prediction model. The performance was measured using Pearson's correlation coefficient and the mean squared error (MAE) between the achieved and predicted results. RESULTS: Measurements of aqueous depth (AQD), anterior chamber volume, anterior chamber angle (ACA) distance, spur-to-spur distance, crystalline lens thickness (LT), and white-to-white distance from ANTERION were highly associated with the ICL vault. The LASSO model using the AQD, ACA distance, and LT showed the best BIC results for postoperative ICL vault prediction. In the validation dataset, the LASSO model showed the strongest correlation (r = 0.582, P < 0.001) and the lowest MAE (104.7 µm). CONCLUSION: This is the first study to develop a postoperative ICL vault prediction and lens-sizing model based on the ANTERION. As the measurements from ANTERION and other AS-OCT devices are not interchangeable, ANTERION may be used for optimal ICL sizing using our formula. Because our model was developed based on the East Asian population, further studies are needed to explore the role of this prediction model in different populations.

Clinical outcomes of and risk factors for secondary infection in patients with severe COVID-19: a multicenter cohort study in South Korea.

BACKGROUND/AIMS: Secondary infection with influenza virus occurs in critically ill patients and is associated with substantial morbidity and mortality; however, there is limited information about it in patients with severe coronavirus disease 2019 (COVID-19). Thus, we investigated the clinical outcomes of and risk factors for secondary infections in patients with severe COVID-19. METHODS: This study included patients with severe COVID-19 who were admitted to seven hospitals in South Korea between February 2020 to February 2021. Multivariate logistic regression analyses were performed to assess factors associated with the risk of secondary infections. RESULTS: Of the 348 included patients, 104 (29.9%) had at least one infection. There was no statistically significant difference in the 28-day mortality (17.3% vs. 12.3%, p = 0.214), but in-hospital mortality was higher (29.8% vs. 15.2%, p = 0.002) in the infected group than in the non-infected group. The risk factors for secondary infection were a high frailty scale (odds ratio [OR], 1.314; 95% confidence interval [CI], 1.123 to 1.538; p = 0.001), steroid use (OR, 3.110; 95% CI, 1.164 to 8.309; p = 0.024), and the application of mechanical ventilation (OR, 4.653; 95% CI, 2.533 to 8.547; p < 0.001). CONCLUSION: In-hospital mortality was more than doubled in patients with severe COVID-19 and secondary infections. A high frailty scale, the use of steroids and application of mechanical ventilation were risk factors for secondary infection.

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Implementation of higher dose (HD) thromboprophylaxis has been considered in patients infected with coronavirus disease 2019 (COVID-19). Our aim was to compare HD to standard dose (SD) thromboprophylaxis in COVID-19 patients. The protocol is registered on PROSPERO (CRD42021284808). We searched for randomised controlled studies (CENTRAL, Embase, Medline and medRxviv) that compared HD to SD anticoagulation in COVID-19 and analysed outcomes such as mortality, thrombotic events, bleedings, and disease progression. The statistical analyses were made using the random effects model. Fourteen articles were included (6253 patients). HD compared with SD showed no difference in mortality (OR 0.83 [95% CI 0.54−1.28]). The use of HD was associated with a decreased risk of thrombosis (OR 0.58 [95% CI 0.44−0.76]), although with an increased risk of major bleeding (OR 1.64 [95% CI 1.25−2.16]). The cohort with D-dimer < 1 mg/mL showed no effect (OR 1.19 [95% CI 0.67−2.11]), but in the case of D-dimer > 1 mg/mL, a tendency of lower risk in the HD group was observed (OR 0.56 [95% CI 0.31−1.00]). The need for intubation in moderately ill patients showed a nonsignificant lower likelihood in the HD group (OR 0.82 [95% CI 0.63−1.08]). We cannot advocate for HD in all COVID-19 patients, although it shows some nonsignificant benefits on disease progression in those with elevated D-dimer who do not need ICU admission.

In-hospital mortality prediction using frailty scale and severity score in elderly patients with severe COVID-19.

BACKGROUND: Elderly patients with coronavirus disease 2019 (COVID-19) have a high disease severity and mortality. However, the use of the frailty scale and severity score to predict in-hospital mortality in the elderly is not well established. Therefore, in this study, we investigated the use of these scores in COVID-19 cases in the elderly. METHODS: This multicenter retrospective study included severe COVID-19 patients admitted to seven hospitals in Republic of Korea from February 2020 to February 2021. We evaluated patients' Acute Physiology and Chronic Health Evaluation (APACHE) II score; confusion, urea nitrogen, respiratory rate, blood pressure, 65 years of age and older (CURB-65) score; modified early warning score (MEWS); Sequential Organ Failure Assessment (SOFA) score; clinical frailty scale (CFS) score; and Charlson comorbidity index (CCI). We evaluated the predictive value using receiver operating characteristic (ROC) curve analysis. RESULTS: The study included 318 elderly patients with severe COVID-19 of whom 237 (74.5%) were survivors and 81 (25.5%) were non-survivors. The non-survivor group was older and had more comorbidities than the survivor group. The CFS, CCI, APACHE II, SOFA, CURB-65, and MEWS scores were higher in the non-survivor group than in the survivor group. When analyzed using the ROC curve, SOFA score showed the best performance in predicting the prognosis of elderly patients (area under the curve=0.766, P<0.001). CFS and SOFA scores were associated with in-hospital mortality in the multivariate analysis. CONCLUSIONS: The SOFA score is an efficient tool for assessing in-hospital mortality in elderly patients with severe COVID-19.

Physical and Chemical Compatibilization Treatment with Modified Aminosilanes for Aluminum/Polyamide Adhesion.

Metal/polymer bilayer composites feature high strength-to-weight ratios and low manufacturing costs despite the weak interfacial adhesion between their components. In this study, aluminum surfaces were modified to generate microporous architectures and hydroxyl moieties by various physical and chemical treatments, including thermal, plasma, anodizing, and hexafluorozirconic acid treatments to overcome the weak interfacial adhesion. The maximum shear strength of the obtained metal/polymer bilayer composites was achieved by anodizing treatment, whereas all treatment methods substantially improved the material toughness. In addition, modified compatibilizing agents with tailorable hydroxyl moieties were applied to enhance the interfacial adhesion using aminoethylaminopropyl trimethoxysilane (AEAPS) and modified AEAPS as a coupling agent. AEAPS modified by monoepoxide (glycidol) produced the strongest positive effect on the composite mechanical properties. These findings can be useful in a myriad of metal/polymer multilayer composites.

Clinical Experiences of High-Risk Pulmonary Thromboembolism Receiving Extracorporeal Membrane Oxygenation in Single Institution.

BACKGROUND: The main cause of death in pulmonary embolism (PE) is right-heart failure due to acute pressure overload. In this sense, extracorporeal membrane oxygenation (ECMO) might be useful in maintaining hemodynamic stability and improving organ perfusion. Some previous studies have reported ECMO as a bridge to reperfusion therapy of PE. However, little is known about the patients that benefit from ECMO. METHODS: Patients who underwent ECMO due to pulmonary thromboembolism at a single university-affiliated hospital between January 2010 and December 2018 were retrospectively reviewed. RESULTS: During the study period, nine patients received ECMO in high-risk PE. The median age of the patients was 60 years (range, 22-76 years), and six (66.7%) were male. All nine patients had cardiac arrests, of which three occurred outside the hospital. All the patients received mechanical support with veno-arterial ECMO, and the median ECMO duration was 1.1 days (range, 0.2-14.0 days). ECMO with anticoagulation alone was performed in six (66.7%), and ECMO with reperfusion therapy was done in three (33.3%). The 30-day mortality rate was 77.8%. The median time taken from the first cardiac arrest to initiation of ECMO was 31 minutes (range, 30-32 minutes) in survivors (n=2) and 65 minutes (range, 33-482 minutes) in non-survivors (n=7). CONCLUSION: High-risk PE with cardiac arrest has a high mortality rate despite aggressive management with ECMO and reperfusion therapy. Early decision to start ECMO and its rapid initiation might help save those with cardiac arrest in high-risk PE.

ROX index and SpO2/FiO2 ratio for predicting high-flow nasal cannula failure in hypoxemic COVID-19 patients: A multicenter retrospective study.

BACKGROUND: The ratio of oxygen saturation (ROX) index, defined as the ratio of oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate, can help identify patients with hypoxemic respiratory failure at high risk for intubation following high-flow nasal cannula (HFNC) initiation; however, whether it is effective for predicting intubation in coronavirus disease 2019 (COVID-19) patients receiving HFNC remains unknown. Moreover, the SpO2/FiO2 ratio has been assessed as a prognostic marker for acute hypoxemic respiratory failure. This study aimed to determine the utility of the ROX index and the SpO2/FiO2 ratio as predictors of failure in COVID-19 patients who received HFNC. METHODS: This multicenter study was conducted in seven university-affiliated hospitals in Korea. Data of consecutive hospitalized patients diagnosed with COVID-19 between February 10, 2020 and February 28, 2021 were retrospectively reviewed. We calculated the ROX index and the SpO2/FiO2 ratio at 1 h, 4 h, and 12 h after HFNC initiation. The primary outcome was HFNC failure defined as the need for subsequent intubation despite HFNC application. The receiver operating characteristic curve analysis was used to evaluate discrimination of prediction models for HFNC failure. RESULTS: Of 1,565 hospitalized COVID-19 patients, 133 who received HFNC were analyzed. Among them, 63 patients (47.4%) were successfully weaned from HFNC, and 70 (52.6%) were intubated. Among patients with HFNC failure, 32 (45.7%) died. The SpO2/FiO2 ratio at 1 h after HFNC initiation was an important predictor of HFNC failure (AUC 0.762 [0.679-0.846]). The AUCs of SpO2/FiO2 ratio at 4 h and ROX indices at 1 h and 4 h were 0.733 (0.640-0.826), 0.697 (0.597-0.798), and 0.682 (0.583-0.781), respectively. Multivariable analysis showed that the patients aged ≥70 years are 3.4 times more likely to experience HFNC failure than those aged <70 years (HR 3.367 [1.358-8.349], p = 0.009). The SpO2/FiO2 ratio (HR 0.983 [0.972-0.994], p = 0.003) at 1 h was significantly associated with HFNC failure. CONCLUSIONS: The SpO2/FiO2 ratio following HFNC initiation was an acceptable predictor of HFNC failure. The SpO2/FiO2 ratio may be a good prognostic marker for predicting intubation in COVID-9 patients receiving HFNC.

Lower Driving Pressure and Neuromuscular Blocker Use Are Associated With Decreased Mortality in Patients With COVID-19 ARDS.

BACKGROUND: The impact of mechanical ventilation parameters and management on outcomes of patients with coronavirus disease 2019 (COVID-19) ARDS is unclear. METHODS: This multi-center observational study enrolled consecutive mechanically ventilated patients with COVID-19 ARDS admitted to one of 7 Korean ICUs between February 1, 2020-February 28, 2021. Patients who were age < 17 y or had missing ventilation parameters for the first 4 d of mechanical ventilation were excluded. Multivariate logistic regression was used to identify which strategies or ventilation parameters that were independently associated with ICU mortality. RESULTS: Overall, 129 subjects (males, 60%) with a median (interquartile range) age of 69 (62-78) y were included. Neuromuscular blocker (NMB) use and prone positioning were applied to 76% and 16% of subjects, respectively. The ICU mortality rate was 37%. In the multivariate analysis, higher dynamic driving pressure (ΔP) values during the first 4 d of mechanical ventilation were associated with increased mortality (adjusted odds ratio 1.16 [95% CI 1.00-1.33], P = .046). NMB use was associated with decreased mortality (adjusted odds ratio 0.27 [95% CI 0.09-0.81], P = .02). The median tidal volume values during the first 4 d of mechanical ventilation and the ICU mortality rate were significantly lower in the NMB group than in the no NMB group. However, subjects who received NMB for ≥ 6 d (vs < 6 d) had higher ICU mortality rate. CONCLUSIONS: In subjects with COVID-19 ARDS receiving mechanical ventilation, ΔP during the first 4 d of mechanical ventilation was independently associated with mortality. The short-term use of NMB facilitated lung-protective ventilation and was independently associated with decreased mortality.

Comparison of Clinical Characteristics and Outcomes of Younger and Elderly Patients with Severe COVID-19 in Korea: A Retrospective Multicenter Study.

Old age is associated with disease severity and poor prognosis among coronavirus disease 2019 (COVID-19) cases; however, characteristics of elderly patients with severe COVID-19 are limited. We aimed to assess the clinical characteristics and outcomes of patients hospitalized with severe COVID-19 at tertiary care centers in South Korea. This retrospective multicenter study included patients with severe COVID-19 who were admitted at seven hospitals in South Korea from 2 February 2020 to 28 February 2021. The Cox regression analyses were performed to assess factors associated with the in-hospital mortality. Of 488 patients with severe COVID-19, 318 (65.2%) were elderly (≥65 years). The older patient group had more underlying diseases and a higher severity score than the younger patient group. The older patient group had a higher in-hospital mortality rate than the younger patient group (25.5% versus 4.7%, p-value < 0.001). The in-hospital mortality risk factors among patients with severe COVID-19 included age, acute physiology and chronic health evaluation II score, presence of diabetes and chronic obstructive lung disease, high white blood cell count, low neutrophil-lymphocyte ratio and platelet count, do-not-resuscitate order, and treatment with invasive mechanical ventilation. In addition to old age, disease severity and examination results must be considered in treatment decision-making.

Late Failure of High-Flow Nasal Cannula May Be Associated with High Mortality in COVID-19 Patients: A Multicenter Retrospective Study in the Republic of Korea.

The aim of this study was to determine whether the late failure of high-flow nasal cannula (HFNC) is associated with mortality in patients with coronavirus disease 2019 (COVID-19). This multicenter study included seven university-affiliated hospitals in the Republic of Korea. We collected the data of patients hospitalized with COVID-19 between 10 February 2020 and 28 February 2021. Failure of HFNC was defined as the need for mechanical ventilation despite HFNC application. According to the time of intubation, HFNC failure was divided into early failure (within 48 h) and late failure (after 48 h). During the study period, 157 patients received HFNC and 133 were eligible. Among them, 70 received mechanical ventilation. The median time from HFNC initiation to intubation of the early failure group was 4.1 h (interquartile range [IQR]: 1.1-13.5 h), and that of the late failure group was 70.9 h (IQR: 54.4-145.4 h). Although the ratio of pulse oximetry/fraction of inspired oxygen (ROX index) within 24 h of HFNC initiation tended to be lower in the early failure group than in the late failure group, the ROX index before two hours of intubation was significantly lower in the late failure group (odds ratio [OR], 5.74 [IQR: 4.58-6.98] vs. 4.80 [IQR: 3.67-5.97], p = 0.040). The late failure of HFNC may be associated with high mortality in COVID-19 patients with acute respiratory failure.

Rapid Tumor Targeting of Renal-Clearable ZW800-1 Conjugate for Efficient Photothermal Cancer Therapy.

The combination of near-infrared (NIR) fluorophores and photothermal therapy (PTT) provides a new opportunity for safe and effective cancer treatment. However, the precise molecular design of functional NIR fluorophores with desired properties, such as high tumor targetability and low nonspecific uptake, remains challenging. In this study, a renal-clearable NIR fluorophore conjugate with high tumor targetability was developed for efficient photothermal cancer therapy. The isoniazid (INH)-ZW800-1 conjugate (INH-ZW) was synthesized by conjugating an antibiotic drug, INH, with a well-known zwitterionic NIR fluorophore, ZW800-1, to improve in vivo performance and fluorescence-guided cancer phototherapy. INH-ZW not only showed rapid tumor accumulation without nonspecific tissue/organ uptake within 1 h after the injection but also generated thermal energy to induce cancer cell death under NIR laser irradiation. Compared with previously reported ZW800-1 conjugates, INH-ZW preserved the ideal biodistribution of ZW800-1 and facilitated improved tumor targeting and PTT. Together, these results demonstrate that the INH-ZW conjugate has great potential to serve as an effective PTT agent capable of rapid tumor targeting and high renal clearance, with excellent photothermal efficacy.

Bioinspired Camellia japonica carbon dots with high near-infrared absorbance for efficient photothermal cancer therapy.

Since carbon dots (CDs) exhibit excellent biocompatibility, low cytotoxicity, near-infrared (NIR) absorbance, and superior photostability, many types of CDs are considered as powerful candidates for photothermal therapy (PTT) applications. However, the development of a desirable CD is still difficult due to insufficient photothermal conversion, thus resulting in the use of high laser power densities at a high dose of CDs for the PTT effect. Herein, bioinspired sulfur-doped CDs (S-CDs) with strong NIR absorbance were prepared from Camellia japonica flowers via a facile hydrothermal method for enhancing the photothermal conversion efficiency. The as-prepared S-CDs exhibited various advantages including cost-effective preparation, good water-solubility, high biocompatibility, intense NIR absorption, and excellent photothermal effect with robust photostability. Most importantly, the optimal low dose of S-CDs (45 µg mL-1) successfully led to efficient PTT performance with a high photothermal conversion efficiency (55.4%) under moderate laser power (808 nm, 1.1 W cm-2) for safe and effective cancer therapy.