Artificial intelligence-enabled quantitative phase imaging methods for life sciences.

Quantitative phase imaging, integrated with artificial intelligence, allows for the rapid and label-free investigation of the physiology and pathology of biological systems. This review presents the principles of various two-dimensional and three-dimensional label-free phase imaging techniques that exploit refractive index as an intrinsic optical imaging contrast. In particular, we discuss artificial intelligence-based analysis methodologies for biomedical studies including image enhancement, segmentation of cellular or subcellular structures, classification of types of biological samples and image translation to furnish subcellular and histochemical information from label-free phase images. We also discuss the advantages and challenges of artificial intelligence-enabled quantitative phase imaging analyses, summarize recent notable applications in the life sciences, and cover the potential of this field for basic and industrial research in the life sciences.

Synthesis of 2,3-Benzotropones via Palladium(II)-Catalyzed Aerobic Dehydrogenation from 1-Benzosuberones and Sequential Diels-Alder Reaction to Yield Benzobicyclo[3.2.2]nonenones.

An approach to 2,3-benzotropone from 1-benzosuberone via palladium(II)-catalyzed aerobic dehydrogenation was developed. This method first provided a catalytic route to various 2,3-benzotropones from their corresponding 1-benzosuberones in good yields. In addition, the reaction could be applied to a one-pot Diels-Alder reaction with maleimide, providing a complex benzobicyclo[3.2.2]nonenone in ≤90% yield. Kinetic analysis supporting our proposed mechanism was also performed, underscoring the robustness of the developed synthetic pathway.

Understanding experiences of cancer-related fatigue in patients with lung cancer after their cancer treatment: a qualitative content analysis.

PURPOSE: Cancer-related fatigue (CRF) is an important symptom affecting the quality of life of patients with lung cancer. However, research on the characteristics of CRF in lung cancer and their relationship to cancer treatment is limited. We aimed to explore the unique features of CRF in patients with lung cancer, and investigate the influencing factors. METHODS: Semi-structured interviews were conducted with 21 adult patients with lung cancer until data saturation was reached. The collected data were analyzed using qualitative content analysis. An inductive coding process and deductive content analysis incorporating the established CRF domains were employed. Patient data from electronic medical records were used for data triangulation. RESULTS: The analysis revealed five themes of CRF: (1) energy depletion, the double burden of illness and treatment, and daily life impediments; (2) feeling down and anxious; (3) neurovascular disturbances and changes in sensory perception; (4) cognitive impairment; and (5) personal and social isolation. CRF tended to improve over time, except for persistent emotional fatigue beyond 6 months. Patients who underwent surgery followed by adjuvant cancer treatment exhibited the most diverse CRF symptoms. The concurrent chemoradiation therapy group experienced significant physical fatigue, whereas the radiosurgery group reported distinct emotional fatigue. Certain factors, such as exercise, can serve as both alleviating and aggravating factors for CRF. CONCLUSION: Tailored interventions that take into account the multidimensional symptoms of CRF and patient characteristics are crucial. These findings will guide healthcare professionals when implementing patient-centered symptom management and patient education.

Long-term label-free assessments of individual bacteria using three-dimensional quantitative phase imaging and hydrogel-based immobilization.

Three-dimensional (3D) quantitative phase imaging (QPI) enables long-term label-free tomographic imaging and quantitative analysis of live individual bacteria. However, the Brownian motion or motility of bacteria in a liquid medium produces motion artifacts during 3D measurements and hinders precise cell imaging and analysis. Meanwhile, existing cell immobilization methods produce noisy backgrounds and even alter cellular physiology. Here, we introduce a protocol that utilizes hydrogels for high-quality 3D QPI of live bacteria maintaining bacterial physiology. We demonstrate long-term high-resolution quantitative imaging and analysis of individual bacteria, including measuring the biophysical parameters of bacteria and responses to antibiotic treatments.

Quantification of structural heterogeneity in H&E stained clear cell renal cell carcinoma using refractive index tomography.

Clear cell renal cell carcinoma (ccRCC) is a common histopathological subtype of renal cancer and is notorious for its poor prognosis. Its accurate diagnosis by histopathology, which relies on manual microscopic inspection of stained slides, is challenging. Here, we present a correlative approach to utilize stained images and refractive index (RI) tomography and demonstrate quantitative assessments of the structural heterogeneities of ccRCC slides obtained from human patients. Machine-learning-assisted segmentation of nuclei and cytoplasm enabled the quantification at the subcellular level. Compared to benign regions, malignant regions exhibited a considerable increase in structural heterogeneities. The results demonstrate that RI tomography provides quantitative information in synergy with stained images on the structural heterogeneities in ccRCC.

Hybrid Method Incorporating a Rule-Based Approach and Deep Learning for Prescription Error Prediction.

INTRODUCTION: Recently, automated detection has been a new approach to address the risks posed by prescribing errors. This study focused on prescription errors and utilized real medical data to supplement the Drug Utilization Review (DUR)-based rules, the current prescription error detection method. We developed a new hybrid method through artificial intelligence for prescription error prediction by utilizing actual detection accuracy improvement to reduce 'warning fatigue' for doctors and improve medical care quality. OBJECT: This study was conducted in the Department of Pediatrics, targeting children sensitive to drugs to develop a prescription error detection system. Based on the DUR prescription history, 15,281 patient-level observations of children from Konyang University Hospital (KYUH)'s common data model (CDM) and DUR were collected and analyzed retrospectively. METHOD: Among the CDM data, inspection information was interlocked with DUR and reflected as standard information for model development; this included outpatient prescriptions from January 1 to December 31, 2018. Through consultation with pediatric clinicians, rule definitions and model development were conducted for 35 drugs, with 137,802 normal and 1609 prescription errors. RESULTS: We developed a novel hybrid method of error detection in the form of an advanced rule-based deep neural network (ARDNN), which showed the expected performance (precision: 72.86, recall: 81.01, F1 score: 76.72) and reduced alarm pop-up alert fatigue to below 10%. We also created an ARDNN-based comprehensive dashboard that allows doctors to monitor prescription errors with alarm pop-ups when prescribing medications. CONCLUSION: These results can advance the existing rule-based model by developing a prescription error detection model using deep learning. This method can improve overall medical efficiency and service quality by reducing doctors' fatigue.

Synthesis of Xanthones via Copper(II)-Catalyzed Dehydrogenative Cyclization and Successive Aromatization in a One-Step Sequence.

In this study, an unprecedented approach to the xanthone scaffold from cyclohexyl(2-hydroxyphenyl)methanone via dehydrogenative cyclization and a successive aromatization cascade is reported. This methodology affords a novel route to the privileged structure with a wide substrate scope (a total of 29 compounds, ≤96% yield) in a highly atom-economic manner.

Syntheses of 1H-Indoles, Quinolines, and 6-Membered Aromatic N-Heterocycle-Fused Scaffolds via Palladium(II)-Catalyzed Aerobic Dehydrogenation under Alkoxide-Free Conditions.

Aromatic N-heterocycle-fused scaffolds such as indoles and quinolines are important core structures found in various bioactive natural products and synthetic compounds. Recently, various dehydrogenation methods with the help of alkoxides, known to significantly promote dihydro- or tetrahydro-heterocycles to be oxidized, were developed for the heterocycle synthesis. However, these approaches are sometimes unsuitable due to resulting undesired side reactions such as reductive dehalogenation. Herein, expedient syntheses of 1H-indoles, quinolines, and 6-membered N-heterocycle-fused scaffolds from their hydrogenated forms through palladium(II)-catalyzed aerobic dehydrogenation under alkoxide-free conditions are reported. A total of 48 compounds were successfully synthesized with a wide range of functional groups including halogens (up to 99% yield). These methodologies provide facile routes for various privileged structures possessing aromatic N-heterocycles without the help of alkoxides, in highly efficient manners.

Synthesis of meta-(Indol-3-yl)phenols from Indoles and Cyclohexenone via Palladium(II)-Catalyzed Oxidative Heck Reaction and Dehydrogenative Aromatization in a One-Step Sequence.

Facile construction of a meta-(indol-3-yl)phenol framework with a wide substrate scope (a total of 25 compounds) via a palladium(II)-catalyzed oxidative Heck reaction and dehydrogenative aromatization in a one-step sequence is reported. This methodology affords a novel route for the privileged structures that are challenging to access via a direct link between indole and phenol, in a highly efficient and atom-economical manner.

Divergent synthesis of flavones and flavanones from 2'-hydroxydihydrochalcones via palladium(ii)-catalyzed oxidative cyclization.

Divergent and versatile synthetic routes to flavones and flavanones via efficient Pd(ii) catalysis are disclosed. These Pd(ii) catalyses expediently provide a variety of flavones and flavanones from 2'-hydroxydihydrochalcones as common intermediates, depending on oxidants and additives, via discriminate oxidative cyclization sequences involving dehydrogenation, respectively, in a highly atom-economic manner.

School Refusal Successfully Treated With Divalproex.

Divalproex was successfully used in a 7-year-old boy suffering from treatment-refractory school refusal complicated with a mood disturbance and anxiety. Divalproex had demonstrated a rapid effect in reducing school anxiety and improving school attendance after multiple failures of other agents. Divalproex may be an effective agent for treating school refusal in children with emotional and/or behavior disturbances.

Isolation of endothelial progenitor cells from cord blood and induction of differentiation by ex vivo expansion.

Endothelial progenitor cells (EPCs) have been reported to possess the capacity to colonize vascular grafts and hold promise for therapeutic neovascularization. However, limited quantities of EPCs have been the major factor impeding effective research on vasculoangiogenesis. In this study, cytokine and culture conditions necessary for the provision of large quantities of endothelial cells (ECs) were investigated. Cord blood was collected from 18 normal full-term deliveries and CD34+ cells were isolated by MACS system (Miltenyi Biotech, Bergish-Gladbach, Germany). To evaluate the effect of cytokines, CD34+ cells were cultured with various cytokine combinations, such as stem cell factor (SCF), flt3-ligand (FL), and thrombopoietin (TPO) with vascular endothelial growth factor (VEGF), interleukin-1 beta , fibroblast growth factor-basic (FGF-b) as basic cytokines. The quantities of non-adherent and adherent cells were the greatest with SCF, FL and TPO. The addition of TPO to all other cytokines significantly increased the number of non-adherent and adherent cells (p< 0.05, Wilcoxon rank sum test). After four weeks of culture, adherent cells expressed endothelial specific markers such as KDR, CD31 and CD62E. Typical morphology of ECs was observed during culture, such as cord-like structure and cobblestone appearance, suggesting that the adherent cells were consistent with ECs. In this study, the experimental conditions that optimize the production of ECs for therapeutic neovascularization were described. And it was possibly suggested that TPO plays a major role in differentiation from EPCs to ECs.

Induction of burst suppression or coma using intravenous anesthetics in refractory status epilepticus.

General anesthetic-induced coma therapy has been recommended for the treatment of refractory status epilepticus (RSE). However, the influence of electroencephalographic (EEG) burst suppression (BS) on outcomes still remains unclear. This study investigated the impact of intravenous anesthetic-induced BS on the prognosis of RSE using a retrospective analysis of all consecutive adult patients who received intravenous anesthetic treatment for RSE at the Seoul National University Hospital between January 2006 and June 2011. Twenty-two of the 111 episodes of RSE were enrolled in this study. Of the 22 RSE patients, 12 (54.5%) were women and 18 (81.4%) exhibited generalized convulsive status epilepticus. Sixteen patients (72.7%) were classified as having acute symptomatic etiology, including three patients with anoxic encephalopathy, and others with remote symptomatic etiology. Only two patients (9.1%) had a favorable Status Epilepticus Severity Score (0-2) at admission. All patients received midazolam (MDZ) as a primary intravenous anesthetic drug for RSE treatment; three (13.6%) received MDZ and propofol, and one (4.5%) received MDZ and pentobarbital. The rates of mortality and poor outcome at discharge were 13.6% (n=3) and 54.5% (n=12), respectively. While BS was achieved in six (27.5%) patients, it was not associated with mortality or poor outcome. Induced BS was associated with prolonged hospital stay in subgroup analysis when excluding anoxic encephalopathy. Our results suggest that induction of BS for treating RSE did not affect mortality or outcome at discharge and may lead to an increased length of hospital stay.