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BACKGROUND AND AIMS: A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision-making related to periprocedural prophylaxis selection and post-procedural monitoring. METHODS: Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a one-month period. RESULTS: A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on twenty PEP risk factors and 5 prophylactic interventions (rectal non-steroidal anti-inflammatory drugs [NSAID], aggressive hydration, combined rectal NSAID and aggressive hydration, pancreatic duct [PD] stenting, and combined rectal NSAID and PD stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. CONCLUSIONS: This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended post-procedure monitoring.
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In the phase diagram of binary liquid mixtures, a miscibility gap is found with the concomitant liquid-liquid phase separation, wherein temperature is a key parameter in modulating the phase behavior. This includes critical temperatures such as the lower critical solution temperature (LCST) and upper critical solution temperature (UCST). Using a comprehensive approach including molecular dynamics (MD) simulation, graph theoretical analysis and spatial inhomogeneity measurement in an LCST-type mixture, we attempt to establish the relationship between the molecular aggregation pattern and phase behavior in TEA-water mixtures. At lower temperatures of binary liquid mixtures, TEA molecules tend to aggregate while simultaneously interacting with water forming a homogeneous solution. As the temperature increases, these TEA aggregates tend to self-associate by minimizing the interaction with water, which facilitates formation of two distinct liquid phases in the binary liquid. The spatial distribution analysis also reveals that the TEA aggregates compatible with water promote uniform distribution of water molecules, maintaining a homogeneous solution, while the water-incompatible ones generate isolation of water H-bond aggregates, leading to liquid-liquid phase separation in the binary system. This current study on temperature-induced molecular aggregation behavior is anticipated to contribute to a critical understanding of the phase behavior in binary liquid mixtures, including UCST, LCST, and reentrant phase behavior.
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Ketyl radicals are synthetically versatile reactive species, but their applications have been hampered by harsh generation conditions employing highly reducing metals. Recently, the pyridine-boryl radical received wide attention as a promising organic reductant because of its mildness as well as convenience in handling. While probing the utility of the pyridine-boryl radical, our group observed facile pinacol coupling reactivity that had not been known at that time. This serendipitous finding was successfully rendered into a practical synthesis of tetraaryl-1,2-diols in up to 99% yield within 1 h. Subsequently, upon examinations of various reaction manifolds, a diastereoselective ketyl-olefin cyclization was accomplished to produce cycloalkanols such as trans-2-alkyl-1-indanols. Compared to the previous methods, the stereocontrolling ability was considerably enhanced by taking advantage of the structurally modifiable boryl group that would be present near the bond-forming site. In this full account, our synthetic efforts with the O-boryl ketyl radicals are disclosed in detail, covering the discovery, optimization, scope expansion, and mechanistic analysis, including density functional theory (DFT) calculations.
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TLR7/8 agonists are versatile immune stimulators capable of treating various diseases such as viral infections, autoimmune, and cancer. Despite the structural similarity of TLR7/8, their immune stimulation mechanisms and time-course responses significantly differ. In this study, a new series of TLR7-selective agonists was synthesized utilizing the economical building block 2,6-dichloropurine. Compound 27b showed the most potent activity on hTLR7 with an EC50 of 17.53 nM and demonstrated high hTLR7 selectivity (224 folds against TLR8). 27b effectively stimulated the secretion of proinflammatory cytokines in mouse macrophages and enhanced intranasal vaccine efficacy against influenza A virus in vivo. Assessment of humoral and mucosal antibody titers confirmed that 27b elevates IgG and IgA levels, protecting against both homologous and heterologous influenza viral infections. These findings suggest that 27b is a promising candidate as a vaccine adjuvant to prevent viral infections or as a robust immunomodulator with prolonged activity for treating immune-suppressed diseases.
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Administración Intranasal , Diseño de Fármacos , Vacunas contra la Influenza , Purinas , Receptor Toll-Like 7 , Receptor Toll-Like 7/agonistas , Animales , Ratones , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Purinas/farmacología , Purinas/química , Adyuvantes de Vacunas/farmacología , Adyuvantes de Vacunas/química , Relación Estructura-Actividad , Ratones Endogámicos BALB C , Femenino , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Citocinas/metabolismo , Células RAW 264.7 , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/síntesis química , Adyuvantes Inmunológicos/químicaRESUMEN
Whereas the conventional anti-dihalogenation of alkenes is a valuable synthetic tool with highly predictable stereospecificity, the restricted reaction mechanism makes it challenging to alter the diastereochemical course into the complementary syn-dihalogenation process. Only a few notable achievements were made recently by inverting one of the stereocenters after anti-addition using a carefully designed reagent system. Here, we report a conceptually distinctive strategy for the simultaneous double electrophilic activation of the two alkene carbons from the same side. Then, the resulting vicinal leaving groups can be displaced iteratively by nucleophilic halides to complete the syn-dihalogenation. For this purpose, thianthrenium dication is employed, and all possible combinations of chlorine and bromine are added onto internal alkenes successfully, particularly resulting in the syn-dibromination and the regiodivergent syn-bromochlorination.
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Despite recent studies indicating a significant correlation between somatosensory deficits and rehabilitation outcomes, how prevailing somatosensory deficits affect stroke survivors' ability to correct their movements and recover overall remains unclear. To explore how major deficits in somatosensory systems impede stroke survivors' motor correction to various external loads, we conducted a study with 13 chronic stroke survivors who had hemiparesis. An inertial, elastic, or viscous load, which was designed to impose perturbing forces with various force profiles, was introduced unexpectedly during the reaching task using a programmable haptic robot. Participants' proprioception and cutaneous sensation were also assessed using passive movement detection, finger-to-nose, mirror, repositioning, and Weinstein pressure tests. These measures were then analyzed to determine whether the somatosensory measures significantly correlated with the estimated reaching performance parameters, such as initial directional error, positional deviation, velocity deviations, and speed of motor correction were measured. Of 13 participants, 5 had impaired proprioception, as they could not recognize the passive movement of their elbow joint, and they kept showing larger initial directional errors even after the familiarization block. Such continuously found inaccurate initial movement direction might be correlated with the inability to develop the spatial body map especially for calculating the initial joint torques when starting the reaching movement. Regardless of whether proprioception was impaired or not, all participants could show the stabilized, constant reaching movement trajectories. This highlights the role of proprioception especially in the execution of a planned movement at the early stage of reaching movement.
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With the improvement in life quality, the increased focus on health has expedited the rapid development of portable preventative-health-monitoring devices. As one of the most attractive sensing technologies, triboelectric nanogenerators (TENGs) are playing a more and more important role in wearable electronics, machinery condition monitoring, and Internet of Things (IoT) sensors. TENGs possess many advantages, such as ease of fabrication, cost-effectiveness, flexibility, material-selection variety, and the ability to collect low-frequency motion, offering a novel way to achieve health monitoring for human beings in various aspects. In this short review, we initially present the working modes of TENGs based on their applications in health monitoring. Subsequently, the applications of TENG-based preventive health monitoring are demonstrated for different abnormal conditions of human beings, including fall-down detection, respiration monitoring, fatigue monitoring, and arterial pulse monitoring for cardiovascular disease. Finally, the discussion summarizes the current limitations and future perspectives. This short review encapsulates the latest and most influential works on preventive health monitoring utilizing the triboelectric effect for human beings and provides hints and evidence for future research trends.
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Undifferentiated carcinoma of the pancreas (UPC) is a rare, aggressive pancreatic cancer subtype. In addition, there is limited data on optimal management and patients tend to present with unresectable disease. This highlights the need to explore non-surgical treatments, such as chemotherapy and radiotherapy. In 2017, a 40-year-old male was diagnosed with UPC, presenting with a 6 cm mass in the pancreas, encasing the major arteries, indicative of a locally advanced stage. Histopathology confirmed UPC with osteoclast-like giant cells. After nine cycles of modified FOLFIRINOX chemotherapy and concurrent chemoradiotherapy, treatment was stopped in 2018 because of his declining health. Remarkably, despite the cessation of treatment, by 2023, the tumor had shrunk to 3.5 cm with no metabolic activity indicated by FDG-PET/CT. This six-year survival and response to non-surgical treatment highlight potential new avenues for managing unresectable pancreatic cancer, underscoring the need for further comprehensive studies to evaluate these therapeutic strategies.
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Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Adulto , Humanos , Masculino , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sobrevivientes , Supervivientes de CáncerRESUMEN
Recently, video-based action recognition methods using convolutional neural networks (CNNs) achieve remarkable recognition performance. However, there is still lack of understanding about the generalization mechanism of action recognition models. In this paper, we suggest that action recognition models rely on the motion information less than expected, and thus they are robust to randomization of frame orders. Furthermore, we find that motion monotonicity remaining after randomization also contributes to such robustness. Based on this observation, we develop a novel defense method using temporal shuffling of input videos against adversarial attacks for action recognition models. Another observation enabling our defense method is that adversarial perturbations on videos are sensitive to temporal destruction. To the best of our knowledge, this is the first attempt to design a defense method without additional training for 3D CNN-based video action recognition models.
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Generalización Psicológica , Conocimiento , Movimiento (Física) , Redes Neurales de la Computación , Reconocimiento en PsicologíaRESUMEN
BACKGROUND AND AIM: Colorectal cancer (CRC) was the fourth most common cancer in Republic of Korea in 2019. It has a gradually increasing mortality rate, indicating the importance of screening for CRC. Among the various CRC screening test, fecal immunochemical test (FIT) is a simple yet most commonly used. Neverthelss, there have been only few long-term studies on subjects with FIT-positive. Therefore, in this study, we aimed to investigate the risk factors for CRC in FIT-positive patients using the National Health Insurance Service Bigdata database. METHODS: Among 1 737 633 individuals with a FIT screening result for CRC in 2009, 101 143 (5.82%) were confirmed to be FIT positive. The CRC incidence over 10 years (up to 2018) of these participants was investigated using the National Cancer Registry. RESULTS: Out of the 101 143 FIT-positive participants, 4395 (4.35%) were diagnosed with CRC. The FIT-positive patients who underwent a second round of screening showed a 5-year cumulative CRC incidence of approximately 1.25%, whereas those who did not showed an incidence of approximately 3.75%. Among the FIT-positive patients, the CRC incidence in the non-compliance group for the second round of screening was 2.8 times higher than that in the compliance group. CONCLUSIONS: In FIT-positive participants, non-compliance with the second round of screening was identified as a major risk factor for CRC development. It is necessary to establish appropriate strategies for managing risk factors for CRC in FIT-positive patients to increase the rate of compliance with the second round of CRC screening.
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Neoplasias Colorrectales , Detección Precoz del Cáncer , Humanos , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Factores de Riesgo , Programas Nacionales de Salud , Tamizaje Masivo , Heces , Sangre OcultaRESUMEN
Osmolytes, small organic compounds, play a key role in modulating the protein stability in aqueous solutions, but the operating mechanism of the osmolyte remains inconclusive. Here, we attempt to clarify the mode of osmolyte action by quantitatively estimating the microheterogeneity of osmolyte-water mixtures with the aid of molecular dynamics simulation, graph theoretical analysis, and spatial distribution measurement in the four osmolyte solutions of trimethylamine-N-oxide (TMAO), tetramethylurea (TMU), dimethyl sulfoxide, and urea. TMAO, acting as a protecting osmolyte, tends to remain isolated with no formation of osmolyte aggregates while preferentially interacting with water, but there is a strong aggregation propensity in the denaturant TMU solution, characterized by favored hydrophobic interactions between TMU molecules. Taken together, the mechanism of osmolyte action on protein stability is proposed as a comprehensive one that encompasses the direct interactions between osmolytes and proteins and indirect interactions through the regulation of water properties in the osmolyte-water mixtures.
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Metilaminas , Agua , Agua/química , Metilaminas/química , Simulación de Dinámica Molecular , Proteínas , Urea/química , SolucionesRESUMEN
Simultaneous multiple displacements of organic molecules can lead to a large structural reconstruction with increased complexity that would be difficult to access otherwise. Whereas double displacement such as olefin metathesis is well-established, higher-order versions remain much more challenging, because of their intrinsic thermodynamic disadvantages. Here, we describe a newly discovered relayed heteroatom group transfer process between bisthioesters and triaminophosphines as an unusual example of a formal triple displacement. Through the oxygen/nitrogen exchange between the two simple starting materials, in addition to the 1,2-sulfur migration of a putative carbene intermediate, an organized relocation of the O/S/N groups proceeded to give a variety of α,α-disulfenylamides with excellent efficiency under ambient conditions. The experimental and computational mechanistic studies revealed the sequence of the relayed group shifts via an α,α-disulfenyl phosphonium enolate intermediate as well as the dual role of triaminophosphine as both an oxygen acceptor and a nitrogen donor.
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Background: During COVID-19, nursing students experienced variations in on-site clinical practice, such as a combination of on-site and non-face-to-face clinical practice. Although on-site clinical practice is critical for increasing nurses' clinical self-efficacy and developing professional nursing values, there is a lack of knowledge that reflects the current clinical practice environment. Aim: To examine the relationship between on-site clinical practice, nursing professional values, and nursing clinical self-efficacy during the COVID-19 pandemic. Methods: This study is a cross-sectional correlational study design. Demographic characteristics, on-site clinical practice, nursing professional values, and nursing clinical self-efficacy were assessed using an online survey from October 3, 2022, to November 6, 2022. Data were analyzed using descriptive statistics, ANOVA, t-test, Pearson's correlation coefficient, and multiple regression. Results: Of the 86 participants, 18 (20.9%) were male and 68 (79.1%) were female. The duration of the participants' average participation in on-site clinical practice was 39.67 days (61.04%). Nursing professional values significantly influenced clinical self-efficacy (ß=0.379, p<0.001). However, on-site clinical practice was not significantly related to clinical self-efficacy (ß=0.051, p=0.611). In terms of nursing clinical self-efficacy, measuring blood glucose had the highest score. On the other hand, establishing and maintaining intravenous catheters had the lowest scores. Conclusion: Nursing students' professional values were significantly associated with nursing clinical self-efficacy; however, the extent of involvement in on-site clinical practice during the pandemic did not have a significant impact on nursing clinical self-efficacy. Given that this study focused on a single university, it is imperative to replicate this research using diverse samples in the future. In addition, there is a need to establish a range of teaching and learning approaches for clinical practice, including simulation, online learning, and the use of state-of-the-art technology for faculty-student feedback strategies, in anticipation of the need for alternative practices.
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BACKGROUND/AIMS: This study aimed to evaluate the prevalence and natural progression of subepithelial lesions (SELs) in the upper gastrointestinal (UGI) tract. METHODS: The medical records of patients with UGI SELs who underwent endoscopic screening at eight university hospitals between January and December 2010 were retrospectively investigated. The follow-up evaluations were performed until December 2016. RESULTS: UGI SELs were found in 1,044 of the 65,233 participants screened (endoscopic prevalence, 1.60%; the total number of lesions, 1,062; mean age, 55.1±11.2 years; men, 53.6%). The median follow-up period was 48 (range, 8-74) months. SELs were most frequently found in the stomach (63.8%) and had a mean size of 9.9±6.1 mm. Endoscopic ultrasonography (EUS) was performed in 293 patients (28.1%). The most common lesions were leiomyomas, followed by gastrointestinal stromal tumors (GISTs), and ectopic pancreas. The proportions of SELs with malignant potential according to size were 3% (<1 cm), 22% (1-2 cm), 27% (2-3 cm), and 38% (≥3 cm). In gastric SELs larger than 1 cm, resections were performed in 20 patients because of an increase in size, of which 12 were found to be GISTs. CONCLUSION: The prevalence of UGI SELs was 1.60%. Further, 23% of gastric SELs ≥1 cm were precancerous lesions, most followed by EUS and clinical decisions without initial pathological confirmation.
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Quantum light emitters capable of generating single photons with circular polarization and non-classical statistics could enable non-reciprocal single-photon devices and deterministic spin-photon interfaces for quantum networks. To date, the emission of such chiral quantum light relies on the application of intense external magnetic fields, electrical/optical injection of spin-polarized carriers/excitons or coupling with complex photonic metastructures. Here we report the creation of free-space chiral quantum light emitters via the nanoindentation of monolayer WSe2/NiPS3 heterostructures at zero external magnetic field. These quantum light emitters emit with a high degree of circular polarization (0.89) and single-photon purity (95%), independent of pump laser polarization. Scanning diamond nitrogen-vacancy microscopy and temperature-dependent magneto-photoluminescence studies reveal that the chiral quantum light emission arises from magnetic proximity interactions between localized excitons in the WSe2 monolayer and the out-of-plane magnetization of defects in the antiferromagnetic order of NiPS3, both of which are co-localized by strain fields associated with the nanoscale indentations.
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Organoazide rearrangement constitutes versatile synthetic strategies but typically requires an extremely strong acid and/or a high reaction temperature. Our group recently discovered the remarkable accelerating effect of the geminal fluorine substituent that enables the facile rearrangement of azides into imidoyl fluorides without the aid of acid under much milder reaction conditions. The role of geminal fluorine was elucidated by both experimental and computational investigations. This new reactivity led to the development of a practical one-step tandem preparative method for potentially useful and bench-stable imidoyl fluorides from a wide range of structurally diverse geminal chlorofluorides. Our additional efforts to expand the reaction scope regarding the migrating group, halogen, and carbonyl function are described, and the synthetic utility of the imidoyl fluoride products was demonstrated in hopes of promoting the use of this under-appreciated functional group in the synthetic organic community.
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Transition metal dichalcogenide heterostructures provide a versatile platform to explore electronic and excitonic phases. As the excitation density exceeds the critical Mott density, interlayer excitons are ionized into an electron-hole plasma phase. The transport of the highly non-equilibrium plasma is relevant for high-power optoelectronic devices but has not been carefully investigated previously. Here, we employ spatially resolved pump-probe microscopy to investigate the spatial-temporal dynamics of interlayer excitons and hot-plasma phase in a MoSe2/WSe2 twisted bilayer. At the excitation density of â¼1014 cm-2, well exceeding the Mott density, we find a surprisingly rapid initial expansion of hot plasma to a few microns away from the excitation source within â¼0.2 ps. Microscopic theory reveals that this rapid expansion is mainly driven by Fermi pressure and Coulomb repulsion, while the hot carrier effect has only a minor effect in the plasma phase.
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This study experimentally investigated the evaporation and wetting transition behavior of fakir droplets on five different microstructured surfaces. Diamond-like carbon was introduced as the substrate, and the influence of varying the width, height, and pitch of the micropillars was assessed. The experimental results showed that the interfacial properties of the surfaces change the evaporation behavior and the starting point of the wetting transition. An important result of this study is the demonstration of a slippery superhydrophobic surface with low depinning force that suppresses the transition from the Cassie-Baxter state to the Wenzel state for microdroplets less than 0.37 mm in diameter, without employing large pillar height or multiscale roughness. By selecting an appropriate pillar pitch and employing tapered micropillars with small pillar widths, the solid-liquid contact at the three-phase contact line was reduced and low depinning forces were obtained. The underlying mechanism by which slippery superhydrophobic surfaces suppress wetting transitions is also discussed. The accuracy of the theoretical models for predicting the critical transition parameters was assessed, and a numerical model was developed in the surface evolver to compute the penetration of the droplet bottom meniscus within the micropillars.