High-level production of keratinocyte growth factor 2 in Escherichia coli.

Recombinant human keratinocyte growth factor 2 (KGF-2), also known as repifermin, is used in various therapeutic applications. However, KGF-2 production has not been optimized for facilitating large-scale production. Therefore, we attempted to attain high-level production of bioactive KGF-2. KGF-2 was fused with 6HFh8 (6HFh8-KGF-2) at the tobacco etch virus protease cleavage site. The 6HFh8-KGF-2 was expressed in Escherichia coli with high expression levels of approximately 33% and 20% of soluble protein in flask culture and 5 L fermentation, respectively. 6HFh8-KGF-2 was purified via nickel affinity chromatography. To maintain a stable form of KGF-2, the conditions of the cleavage reaction were optimized based on the isoelectric point. KGF-2 was purified via ion-exchange chromatography to high purity (>99%) with an optimal purification yield (91%). Circular dichroism spectroscopy demonstrated that purified KGF-2 had a secondary structure and thermal stability similar to that of commercial KGF-2. Bioactivity assays indicated that purified KGF-2 could induce MCF-7 cell proliferation in the same manner as commercial KGF-2. These results demonstrate that bioactive KGF-2 was overexpressed in E. coli and purified to high quality. Our findings indicated that bioactive KGF-2 can be produced in large quantities in E. coli.

Production of a 135-residue long N-truncated human keratinocyte growth factor 1 in Escherichia coli.

BACKGROUND: Palifermin (trade name Kepivance®) is an amino-terminally truncated recombinant human keratinocyte growth factor 1 (KGF-1) with 140 residues that has been produced using Escherichia coli to prevent and treat oral mucositis following radiation or chemotherapy. In this study, an amino-terminally shortened KGF-1 variant with 135 residues was produced and purified in E. coli, and its cell proliferation activity was evaluated. RESULTS: We expressed soluble KGF-1 fused to thioredoxin (TRX) in the cytoplasmic fraction of E. coli to improve its production yield. However, three N-truncated forms (KGF-1 with 140, 138, and 135 residues) were observed after the removal of the TRX protein from the fusion form by cleavage of the human enterokinase light chain C112S (hEKL C112S). The shortest KGF-1 variant, with 135 residues, was expressed by fusion with TRX via the hEKL cleavage site in E. coli and purified at high purity (> 99%). Circular dichroism spectroscopy shows that purified KGF-1135 had a structure similar to that of the KGF-1140 as a random coiled form, and MCF-7 cell proliferation assays demonstrate its biological activity. CONCLUSIONS: We identified variations in N-terminus-truncated KGF-1 and selected the most stable form. Furthermore, by a simple two-step purification, highly purified KGF-1135 was obtained that showed biological activity. These results demonstrate that KGF-1135 may be considered an alternative protein to KGF-1.

Impact of COVID-19 on Out-of-Hospital Cardiac Arrest in Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global public health crisis that has had a significant impact on emergency medical services (EMS). Several studies have reported an increase in the incidence of out-of-hospital cardiac arrest (OHCA) and a decreased survival due to COVID-19, which has been limited to a short period or has been reported in some regions. This study aimed to investigate the effect of COVID-19 on OHCA patients using a nationwide database. METHODS: We included adult OHCA patients treated by EMS providers from January 19, 2019 to January 20, 2021. The years before and after the first confirmed case in Korea were set as the non-COVID-19 and COVID-19 periods, respectively. The main exposure of interest was the COVID-19 period, and the primary outcome was prehospital return of spontaneous circulation (ROSC). Other OHCA variables were compared before and after the COVID-19 pandemic and analyzed. We performed a multivariable logistic regression analysis to understand the independent effect of the COVID-19 period on prehospital ROSC. RESULTS: The final analysis included 51,921 eligible patients, including 25,355 (48.8%) during the non-COVID-19 period and 26,566 (51.2%) during the COVID-19 period. Prehospital ROSC deteriorated during the COVID-19 period (10.2% vs. 11.1%, P = 0.001). In the main analysis, the adjusted odds ratios (AORs) for prehospital ROSC showed no significant differences between the COVID-19 and non-COVID-19 periods (AOR [95% confidence interval], 1.02 [0.96-1.09]). CONCLUSION: This study found that the proportion of prehospital ROSC was lower during the COVID-19 period than during the non-COVID-19 period; however, there was no statistical significance when adjusting for potential confounders. Continuous efforts are needed to restore the broken chain of survival in the prehospital phase and increase the survival rate of OHCA patients.

The Impact of the COVID-19 Outbreak on Emergency Medical Service: An Analysis of Patient Transportations and Time Intervals.

BACKGROUND: This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on the Emergency Medical Service (EMS) system in South Korea. The study focused on the differences in EMS time intervals following the COVID-19 outbreak, particularly for patients with fever. METHODS: A retrospective analysis of EMS patient transportation data from 2017 to 2022 was conducted using the national EMS database. RESULTS: Starting from the year 2020, coinciding with the COVID-19 outbreak, all EMS time intervals experienced an increase. For the years 2017 to 2022, the mean response time interval values were 8.6, 8.6, 8.6, 10.2, 12.8, and 11.4 minutes, and the mean scene time interval values were 7.1, 7.2, 7.4, 9.0, 9.8, and 10.9 minutes. The mean transport time interval (TTI) values were 12.1, 12.3, 12.4, 14.2, 16.9, and 16.2 minutes, and the mean turnaround time interval values were 27.6, 27.9, 28.7, 35.2, 42.0, and 43.1 minutes. Fever (≥ 37.5°C) patients experienced more pronounced prolongations in EMS time intervals compared to non-fever patients and had a higher probability of being non-transported. The mean differences in TTI between fever and non-fever patients were 0.8, 0.8, 0.8, 4.3, 4.8, and 3.2 minutes, respectively, from 2017 to 2022. Furthermore, the odds ratios for fever patients being transported to the emergency department were 2.7, 2.9, 2.8, 1.1, 0.8, and 0.7, respectively, from 2017 to 2022. CONCLUSION: The study findings highlight the significant impact of the COVID-19 outbreak on the EMS system and emphasize the importance of ongoing monitoring to evaluate the burden on the EMS system.

Effective production of human growth factors in Escherichia coli by fusing with small protein 6HFh8.

BACKGROUND: Growth factors (GFs) are signaling proteins that affect cellular processes such as growth, proliferation, and differentiation. GFs are used as cosmeceuticals, exerting anti-wrinkle, anti-aging, and whitening effects, and also as pharmaceuticals to treat wounds, growth failure, and oral mucositis. However, in mammalian and bacterial cells, low productivity and expression in inclusion bodies, respectively, of GFs does not satisfy the consumer demand. Here, we aimed to develop a bacterial expression system that produces high yields of soluble GFs that can be purified in their native forms. RESULTS: We present Fh8, an 8-kDa peptide from Fasciola hepatica with an N-terminal hexa-histidine (6HFh8), as a fusion partner for enhanced human GF production in recombinant Escherichia coli. The fusion partner harboring a tobacco etch virus (TEV) protease cleavage site was fused to the N-terminus of 10 human GFs: acidic and basic fibroblast growth factors (aFGF and bFGF, respectively), epidermal growth factor (EGF), human growth hormone (hGH), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor 165 (VEGF165), keratinocyte growth factor 1 (KGF-1), placental growth factor (PGF), stem cell factor (SCF), and tissue inhibitor of metalloproteinase 1 (TIMP-1). The fusion proteins were expressed in E. coli under the control of T7 promoter at three temperatures (25 °C, 30 °C, and 37 °C). All individual fusion proteins, except for SCF and TIMP-1, were successfully overexpressed in cytoplasmic soluble form at more than one temperature. Further, the original aFGF, IGF-1, EGF, and VEGF165 proteins were cleaved from the fusion partner by TEV protease. Five-liter fed-batch fermentation approaches for the 6HFh8-aFGF (lacking disulfide bonds) and 6HFh8-VEGF165 (a cysteine-rich protein) were devised to obtain the target protein at concentrations of 9.7 g/l and 3.4 g/l, respectively. The two GFs were successfully highly purified (> 99% purity). Furthermore, they exerted similar cell proliferative effects as those of their commercial equivalents. CONCLUSIONS: We demonstrated that 6HFh8-GF fusion proteins could be overexpressed on a g/l scale in the cytoplasm of E. coli, with the GFs subsequently highly purified and maintaining their biological activity. Hence, the small protein 6HFh8 can be used for efficient mass-production of various GFs.

Identification of novel immunogenic proteins against Streptococcus parauberis in a zebrafish model by reverse vaccinology.

Streptococcus parauberis is the major infectious agent of streptococcosis in the olive flounder (Paralichthys olivaceus), causing serious economic damage. In this study, we identified potential vaccine candidates against S. parauberis by reverse vaccinology. In total, the 2 out of 21 proteins were identified as vaccine candidates from two available S. parauberis genomes. The membrane-anchored protein SEC10/PgrA and the metal ABC transporter substrate-binding lipoprotein mtsA were potent antigenic proteins based on western blotting with mouse-derived antiserum against whole bacteria of S. parauberis serotypes I and II. In particular, metal ABC transporter substrate-binding lipoprotein (mtsA) showed similar protective immunity to that of whole-cell bacterins against S. parauberis in a zebrafish model. These results suggest that mtsA may be considered as a novel candidate in the development of vaccines against S. parauberis.

Target Temperature Management May Not Improve Clinical Outcomes of Extracorporeal Cardiopulmonary Resuscitation.

PURPOSE: Target temperature management (TTM) and extracorporeal cardiopulmonary resuscitation (ECPR) have been established as important interventions during cardiopulmonary arrest. However, the impact of combined TTM and ECPR on clinical outcomes has not been studied in detail. METHODS: We reviewed the records of 245 patients who received extracorporeal life support (ECLS) between January 2012 and June 2015. Exclusion criteria were as follows: Extracorporeal life support performed for reasons other than cardiac arrest, age less than 18 years, and death within 24 hours. A total of 101 patients were finally included in the study. Twenty-five patients underwent TTM, and 76 patients did not. RESULTS: The patients' mean age was 55 ± 16.7 years. The mean cardiac arrest time was 44.6 ± 33.5 minutes. There were 84 patients whose cardiac arrest was due to a cardiac cause (83.2%) and 79 patients with in-hospital cardiac arrest (78.2%). There was a significant difference in average body temperature during the first 24 hours following ECPR (33.4°C vs 35.6°C; P = .001). The overall favorable neurological outcome rate was 34% and hospital survival rate was 47%. There was no difference in favorable neurological outcomes and hospital survival between the TTM and non-TTM groups (P = .91 and .84, respectively). On multivariate analysis of neurological outcomes and hospital survival, TTM was not a significant prognostic factor. CONCLUSION: We did not observe any benefits of TTM in patients undergoing ECPR. Natural hypothermia or normothermia related to ECLS may explain this result. Further research is needed to understand the role of TTM in ECPR.

High-level production of N-terminal pro-brain natriuretic peptide, as a calibrant of heart failure diagnosis, in Escherichia coli.

Heart failure (HF) is a coronary disease that affects people worldwide and has a high mortality rate. N-terminal pro-brain natriuretic peptide (NT-proBNP) has been proven to be a useful and accurate biomarker for diagnosing systolic HF. Here, we report a strategy for the high-level production of recombinant (r)NT-proBNP in Escherichia coli. An Fh8 tag with six histidines was fused to the N terminus of NT-proBNP along with the recognition site of tobacco etch virus (TEV) protease; the 6HFh8-NT-proBNP fusion peptide was expressed in flask cultures of E. coli in almost completely soluble form. The peptide was purified by HisTrap affinity chromatography, and the N-terminal tag was cleaved by TEV protease. After a second round of HisTrap affinity chromatography to remove the TEV protease and N-terminal tag, rNT-proBNP was isolated with high purity (≥ 98%) by carboxymethyl cation exchange chromatography. The final yield of purified rNT-proBNP (97.5 mg/l of bacterial culture; 3.25 mg/g of wet cell) was 55-fold higher than that reported in previous studies (0.5-1.75 mg/l of bacterial culture). Furthermore, the high cell density E. coli fed-batch culture enabled high-level production of rNT-proBNP in the order of grams per liter. The purified rNT-proBNP was detected by enzyme-linked immunosorbent assay and chemiluminescence enzyme immunoassay using commercial monoclonal antibodies recognizing different epitopes, showing a linear dose-response relationship in the range of tested concentrations (slope = 3.58 and r2 = 0.995). These results demonstrate the efficiency of our process for mass producing (gram-to-liter level) rNT-proBNP with acceptable analytical performance.

Enhanced Hydrogen Production by Co-cultures of Hydrogenase and Nitrogenase in Escherichia coli.

Rhodobacter sphaeroides is a bacterium that can produce hydrogen by interaction with hydrogenase and nitrogenase. We report a hydrogen production system using co-cultivation of hydrogenase in liquid medium and immobilized nitrogenase in Escherichia coli. The recombinant plasmid has been constructed to analyze the effect of hydrogen production on the expression of hupSL hydrogenase and nifHDK nitrogenase isolated from R. sphaeroides. All recombinant E. coli strains were cultured anaerobically, and cells for nitrogenase were immobilized in agar gel, whereas cells for hydrogenase were supplemented on the nitrogenase agar gel. The hupSL hydrogenase has been observed to enhance hydrogen production and hydrogenase activity under co-culture with nifHDK nitrogenase. The maximum hydrogen production has been obtained at an agar gel concentration and a cell concentration for co-culture of 2 % and 6.4 × 10(8) CFU. Thus, co-culture of hupSL hydrogenase and nifHDK nitrogenase provides a promising route for enhancing the hydrogen production and hydrogenase activity.

Predictors of Default from Treatment for Tuberculosis: a Single Center Case-Control Study in Korea.

Default from tuberculosis (TB) treatment could exacerbate the disease and result in the emergence of drug resistance. This study identified the risk factors for default from TB treatment in Korea. This single-center case-control study analyzed 46 default cases and 100 controls. Default was defined as interrupting treatment for 2 or more consecutive months. The reasons for default were mainly incorrect perception or information about TB (41.3%) and experience of adverse events due to TB drugs (41.3%). In univariate analysis, low income (< 2,000 US dollars/month, 88.1% vs. 68.4%, P = 0.015), absence of TB stigma (4.3% vs. 61.3%, P < 0.001), treatment by a non-pulmonologist (74.1% vs. 25.9%, P < 0.001), history of previous treatment (37.0% vs. 19.0%, P = 0.019), former defaulter (15.2% vs. 2.0%, P = 0.005), and combined extrapulmonary TB (54.3% vs. 34.0%, P = 0.020) were significant risk factors for default. In multivariate analysis, the absence of TB stigma (adjusted odd ratio [aOR]: 46.299, 95% confidence interval [CI]: 8.078-265.365, P < 0.001), treatment by a non-pulmonologist (aOR: 14.567, 95% CI: 3.260-65.089, P < 0.001), former defaulters (aOR: 33.226, 95% CI: 2.658-415.309, P = 0.007), and low income (aOR: 5.246, 95% CI: 1.249-22.029, P = 0.024) were independent predictors of default from TB treatment. In conclusion, patients with absence of disease stigma, treated by a non-pulmonologist, who were former defaulters, and with low income should be carefully monitored during TB treatment in Korea to avoid treatment default.

The effect of CbbR-binding affinity to the upstream of cbbF and cfxB on the metabolic effector in Rhodobacter sphaeroides.

Rhodobacter sphaeroides is a non-sulfur photosynthetic bacterium that possesses two cbb operons, cbb I and cbb II , encoding enzymes involved in the Calvin-Bensom-Bassham reductive pentose phosphate pathway of carbon dioxide fixation. In the present study, a number of molecules have been identified that have the ability to alter the in vivo DNA-binding properties of CbbR protein in R. sphaeroides. The CbbR-binding sites on the cbb operon in R. sphaeroides were characterized by chromatin immunoprecipitation (ChIP) assay. The ChIP assay indicated that the CbbR protein binds specifically to the upstream regions cbbF in cbb I operon and cfxB in cbb II operon. The change in the binding of CbbR to the upstream of cbbF and cfxB in the presence of RuBP, fructose 1,6-bisphosphate, NADPH, KH2PO4 was observed under anaerobic, aerobic, aerobic light-dark, and aerobic dark conditions, respectively. From these results, the role of different co-inducer molecules in influencing the interactions of CbbR with the binding site within cbb operon has been ascertained. The biosynthetic intermediates and other potential metabolic effectors have been observed to play an important role in the regulatory mechanism.

Comparison of Dual-Dispatch Protocols on Return of Spontaneous Circulation in Patients with Out-of-Hospital Cardiac Arrest: A Nationwide Observational Study.

Objective: In South Korea, the National Fire Agency (NFA) conducted a pilot project on the advanced life support (ALS) protocol, including epinephrine administration, to improve the survival rate of out-of hospital cardiac arrest (OHCA). Therefore, this study aimed to evaluate the effect of the ALS protocol of NFA on prehospital return of spontaneous circulation (PROSC) in patients with OHCA. Methods: This study was conducted on patients with adult-presumed cardiac arrest between January and December 2020. The main factor of interest was ambulance type according to the ALS protocol, which was divided into dedicated ALS(DA), smartphone-based ALS(SALS), and non-dedicated ALS(Non-DA), and the main analysis factor was PROSC. Multivariate logistic regression analysis was performed. Results: During the study period, a total of 18,031 adult patients with OHCA were treated by the emergency medical service (EMS), including 7,520 (41.71 %) DA, 2,622 (14.54 %) SALS, and 7,889 (43.75 %) Non-DA. The prehospital ROSC ratio was 13.19% for the DA, 11.17% for the SALS, and 7.91% for the Non-DA ambulance (P < 0.01). Compared with that of the DA group, the odds ratio (95% confidence interval [CI]) for PROSC ratio in the SALS and Non-DA groups were 0.97 (0.82-1.15) and 0.57 (0.50-0.65), respectively. It was shown that the PROSC ratio of the DA group was higher than that of the Non-DA group and was not lower than that of the SALS group. Conclusion: ALS protocol intervention was associated with difference in PROSC rates. Therefore, continuous efforts on the systemic implementation of the ALS protocol to improve OHCA outcomes are necessary.

Mechanically robust superamphiphobic aluminum surface with nanopore-embedded microtexture.

A simple fabrication technique was developed for preparing a mechanically robust superamphiphobic surface on an aluminum (Al) plate. Dual geometric architectures with micro- and nanoscale structures were formed on the surface of the Al plate by a combination of simple chemical etching and anodization. This proposed methodology involves (1) fabrication of irregular microscale plateaus on the surface of the Al plate, (2) formation of nanopores, and (3) fluorination. Wettability measurements indicated that the fabricated Al surface became super-repellent toward a broad range of liquids with surface tension in the range 27.5-72 mN/m. By varying the anodization time, we measured and compared the effects of morphological change on the wettability. The adhesion property and mechanical durability of the fabricated superamphiphobic Al surface were evaluated by the Scotch tape and hardness tests, respectively. The results showed that the fabricated Al surface retained mechanical robustness because the down-directed surface made by nanopores on the microtextured surface was durable enough even after high force was applied. Almost no damage of the film was observed, and the surface still exhibited superamphiphobicity after the tests. The fabricated superamphiphobic surface also remained stable after long-term storage. The simple and time-saving fabrication technique can be extended to any large-area three-dimensional surface, making it potentially suitable for large-scale industrial fabrications of mechanically robust superamphiphobic surfaces.

A practical approach to Sasang constitutional diagnosis using vocal features.

BACKGROUND: Sasang constitutional medicine (SCM) is a type of tailored medicine that divides human beings into four Sasang constitutional (SC) types. Diagnosis of SC types is crucial to proper treatment in SCM. Voice characteristics have been used as an essential clue for diagnosing SC types. In the past, many studies tried to extract quantitative vocal features to make diagnosis models; however, these studies were flawed by limited data collected from one or a few sites, long recording time, and low accuracy. We propose a practical diagnosis model having only a few variables, which decreases model complexity. This in turn, makes our model appropriate for clinical applications. METHODS: A total of 2,341 participants' voice recordings were used in making a SC classification model and to test the generalization ability of the model. Although the voice data consisted of five vowels and two repeated sentences per participant, we used only the sentence part for our study. A total of 21 features were extracted, and an advanced feature selection method-the least absolute shrinkage and selection operator (LASSO)-was applied to reduce the number of variables for classifier learning. A SC classification model was developed using multinomial logistic regression via LASSO. RESULTS: We compared the proposed classification model to the previous study, which used both sentences and five vowels from the same patient's group. The classification accuracies for the test set were 47.9% and 40.4% for male and female, respectively. Our result showed that the proposed method was superior to the previous study in that it required shorter voice recordings, is more applicable to practical use, and had better generalization performance. CONCLUSIONS: We proposed a practical SC classification method and showed that our model having fewer variables outperformed the model having many variables in the generalization test. We attempted to reduce the number of variables in two ways: 1) the initial number of candidate features was decreased by considering shorter voice recording, and 2) LASSO was introduced for reducing model complexity. The proposed method is suitable for an actual clinical environment. Moreover, we expect it to yield more stable results because of the model's simplicity.

Study of a vocal feature selection method and vocal properties for discriminating four constitution types.

The voice has been used to classify the four constitution types, and to recognize a subject's health condition by extracting meaningful physical quantities, in traditional Korean medicine. In this paper, we propose a method of selecting the reliable variables from various voice features, such as frequency derivative features, frequency band ratios, and intensity, from vowels and a sentence. Further, we suggest a process to extract independent variables by eliminating explanatory variables and reducing their correlation and remove outlying data to enable reliable discriminant analysis. Moreover, the suitable division of data for analysis, according to the gender and age of subjects, is discussed. Finally, the vocal features are applied to a discriminant analysis to classify each constitution type. This method of voice classification can be widely used in the u-Healthcare system of personalized medicine and for improving diagnostic accuracy.

Biological Influence of Pulmonary Disease Conditions Induced by Particulate Matter on Microfluidic Lung Chips.

Particulate matter (PM10)-induced respiratory illnesses are difficult to investigate in trans-well culture systems. Microphysiological systems offer the capacity to mimic these phenomena to analyze any possible hazards that PM10 exposure poses to respiratory system of Humans. This study proposes an on-chip healthy human lung distal airway model that efficiently reconstitutes in vivo-like environmental conditions in a microfluidic device. The lung-on-chip model comprises a TEER sensor chip and portable microscope for continuous monitoring. To determine the efficacy of our model, we assessed the response to exposure to three PM environmental conditions (mild, average, and severe) and analyzed the relevant in vivo physiological and toxicological data using the airway model. Our results revealed significant increases in the levels of the IL-13, IL-6, and MUC5AC pathological biomarkers, which indicate increased incidences of on-chip asthma and chronic obstructive pulmonary disease conditions. Overall, we deduced that this model will facilitate the identification of potential therapeutics and the prevention of chronic life-threatening toxicities and pandemics such as COVID-19. The proposed system provides basic data for producing an improved in organ-on-chip technology. Supplementary Information: The online version contains supplementary material available at 10.1007/s13206-022-00068-x.

The number and level of first-contact emergency medical services crew and clinical outcomes in out-of-hospital cardiac arrest with dual dispatch response.

OBJECTIVE: This study aimed to evaluate the association between the number and level of emergency medical technicians (EMTs) in the first-contact emergency medical services (EMS) unit and the clinical outcomes of out-of-hospital cardiac arrest (OHCA) with a dual dispatch response. METHODS: Adult nontraumatic EMS-treated OHCAs between 2015 and 2018 in a nationwide database, were enrolled. The main exposure was the number and certification level of first-contact EMS crew: three versus two members, proportion of EMT intermediate level (EMT-I) over 50% versus under or equal to 50%. Good neurologic recovery was selected as the primary outcome. Multilevel multivariable logistic regression analysis was conducted to calculate adjusted odds ratios and confidence intervals. RESULTS: A total of 26,867 patients were enrolled and analyzed. Good neurologic recovery was different across the study groups: 5.4% in the two-member crews, 7.2% in the three-member crews, 5.9% in the low EMT-I proportion crews, and 6.8% in the high EMT-I proportion crews. In the main analysis, statistically significant differences for favorable outcomes were found between the three-member and two-member crews, and the high EMT-I proportion and low EMT-I proportion crews; for good neurologic recovery, adjusted odds ratios (95% confidence interval) were 1.23 (1.06-1.43) for three-member crews, and 1.28 (1.17-1.40) for a high EMT-I proportion. CONCLUSION: The higher number and level of first-contact EMS crew was associated with better neurologic recovery in adult nontraumatic OHCA with a dual-dispatched EMS response.

SperoPredictor: An Integrated Machine Learning and Molecular Docking-Based Drug Repurposing Framework With Use Case of COVID-19.

The global spread of the SARS coronavirus 2 (SARS-CoV-2), its manifestation in human hosts as a contagious disease, and its variants have induced a pandemic resulting in the deaths of over 6,000,000 people. Extensive efforts have been devoted to drug research to cure and refrain the spread of COVID-19, but only one drug has received FDA approval yet. Traditional drug discovery is inefficient, costly, and unable to react to pandemic threats. Drug repurposing represents an effective strategy for drug discovery and reduces the time and cost compared to de novo drug discovery. In this study, a generic drug repurposing framework (SperoPredictor) has been developed which systematically integrates the various types of drugs and disease data and takes the advantage of machine learning (Random Forest, Tree Ensemble, and Gradient Boosted Trees) to repurpose potential drug candidates against any disease of interest. Drug and disease data for FDA-approved drugs (n = 2,865), containing four drug features and three disease features, were collected from chemical and biological databases and integrated with the form of drug-disease association tables. The resulting dataset was split into 70% for training, 15% for testing, and the remaining 15% for validation. The testing and validation accuracies of the models were 99.3% for Random Forest and 99.03% for Tree Ensemble. In practice, SperoPredictor identified 25 potential drug candidates against 6 human host-target proteomes identified from a systematic review of journals. Literature-based validation indicated 12 of 25 predicted drugs (48%) have been already used for COVID-19 followed by molecular docking and re-docking which indicated 4 of 13 drugs (30%) as potential candidates against COVID-19 to be pre-clinically and clinically validated. Finally, SperoPredictor results illustrated the ability of the platform to be rapidly deployed to repurpose the drugs as a rapid response to emergent situations (like COVID-19 and other pandemics).

Optical properties of Si microwires combined with nanoneedles for flexible thin film photovoltaics.

A combined wire structure, made up of longer periodic Si microwires and short nanoneedles, was prepared to enhance light absorption using one-step plasma etching via lithographical patterning. The combined wire array exhibited light absorption of up to ~97.6% from 300 to 1100 nm without an anti-reflection coating. These combined wire arrays on a Si substrate were embedded into a transparent polymer. A large-scale wire-embedded soft film was then obtained by peeling the polymer-embedded wire portion from the substrate. Optically attractive features were present in these soft films, making them suitable for use in flexible silicon solar cell applications.

Intractable Coronary Spasm Requiring Percutaneous Coronary Intervention after Coronary Artery Bypass Grafting in a Patient with Moyamoya Disease.

Moyamoya disease (MMD) is characterized by progressive steno-occlusive lesions of the distal or proximal branch of the internal carotid arteries, and cerebrovascular symptoms are its major complications. Extracranial vascular involvement including the coronary artery has been reported, and some case reports have described variant angina or myocardial infarction. However, no report has yet described a case of myocardial infarction after coronary artery bypass grafting (CABG). Here, we present a patient with MMD who suffered cardiac arrest caused by myocardial infarction due to a coronary spasm after offpump CABG and who was discharged successfully after treatment with a veno-arterial extracorporeal membrane oxygenator and percutaneous coronary intervention.