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Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CLNR) and renal clearance (CLR) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CLNR, and CLR) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance (CLCR). Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.
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Polyhydroxyalkanoate (PHA) is an environmental alternative to petroleum-based plastics because of its biodegradability. The polymer properties of PHA have been improved by the incorporation of different monomers. Traditionally, the monomer composition of PHA has been analyzed using gas chromatography (GC) and nuclear magnetic resonance (NMR), providing accurate monomer composition. However, sequential analysis of the thermal properties of PHA using differential scanning calorimetry (DSC) remains necessary, providing crucial insights into its thermal characteristics. To shorten the monomer composition and thermal property analysis, we directly applied DSC to the analysis of the obtained PHA film and observed a high correlation (r2 = 0.98) between melting enthalpy and the 3-hydroxyhexanoate (3-HHx) mole fraction in the polymer. A higher 3-HHx fraction resulted in a lower melting enthalpy as 3-HHx provided the polymer with higher flexibility. Based on this, we selected the poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(3HB-co-3HHx)) producing strain from Cupriavidus strains that newly screened and transformed with vectors containing P(3HB-co-3HHx) biosynthetic genes, achieving an average error rate below 1.8% between GC and DSC results. Cupriavidus sp. BK2 showed a high 3-HHx mole fraction, up to 10.38 mol%, with Tm (â) = 171.5 and ΔH of Tm (J/g) = 48.0, simultaneously detected via DSC. This study is an example of the expansion of DSC for PHA analysis from polymer science to microbial engineering.
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Anti-PD immunotherapy is currently under investigation in anaplastic thyroid carcinoma (ATC). Tumor cell surface PD-L1 expression is considered predictive of therapeutic response. Although papillary thyroid carcinoma has been widely studied for PD-L1 expression, there are limited data on ATC. In this retrospective multi-institutional study involving 9 centers across Asia, 179 ATCs were assessed for PD-L1 expression using the SP263 (Ventana) clone. A tumor proportion score (TPS) ≥1% was required to consider a case PD-L1-positive. PD-L1 expression was compared with the histological patterns, the type of specimen (small or large), tumor molecular profile (BRAF V600E and TERT promoter mutation status), and patient outcome. PD-L1 expression in any co-existent differentiated thyroid carcinoma (DTC) was evaluated separately and compared with ATC. Most ATCs (73.2%) were PD-L1-positive. The median TPS among positive cases was 36% (IQR 11% to 75%; range 1% to 99%). A high expression (TPS ≥ 50%) was noted in 30.7%. PD-L1-negative cases were more likely to be small specimens (P=0.01). A negative result on small samples, hence, may not preclude expression elsewhere. ATCs having epithelioid and pleomorphic histological patterns were more likely to be PD-L1-positive with higher TPS than sarcomatoid (P<0.01). DTCs were more frequently negative and had lower TPS than ATC (P<0.01). Such PD-L1 conversion from DTC-negative to ATC-positive was documented in 71% of cases with co-existent DTC. BRAF V600E, but not TERT promoter mutations, correlated significantly with PD-L1-positivity rate (P=0.039), reinforcing the potential of combining anti-PD and anti-BRAF V600E drugs. PD-L1 expression, however, did not impact the patient outcome.
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In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
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Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.
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Tecido Adiposo , Regeneração Óssea , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteogênese , Engenharia Tecidual , Alicerces Teciduais , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Tecido Adiposo/citologia , Animais , Transplante de Células-Tronco Mesenquimais/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Diferenciação CelularRESUMO
Recent studies have shown that novel antibody-drug conjugates (ADCs) can improve clinical outcomes in patients with HER2-low breast cancers. This study aimed to investigate alteration of HER2 status during breast cancer progression with an emphasis on HER2-low status. Using 386 paired samples of primary and recurrent breast cancers, HER2 discordance rate between primary and matched recurrent samples, the relationships between HER2 discordance and clinicopathological characteristics and clinical outcomes of the patients were analyzed. HER2 discordance rate between primary breast cancer and first recurrence was 25.9% (κ = 0.586) with mostly zero-to-low (10.6%) or low-to-zero (9.3%) conversion. There was no significant difference in the discordant rates according to type or location of the recurrence. Of 70 cases with a second recurrence, HER2 discordance rate between the primary tumor and the second recurrence was 27.1% (κ = 0.554). HER2 discordance was associated with lower HER2 level, lymphovascular invasion, and progesterone receptor positivity of the primary tumor. In further analyses, HER2-zero-to-low conversion was associated with lymph node metastasis and hormone receptor (HR) positivity, whereas HER2-low-to-zero conversion was associated with HR negativity and triple-negative subtype. In survival analyses, HER2 discordance was associated with decreased overall survival of patients in the HR-positive group but not in the HR-negative group. Furthermore, patients with HER2-low-to-zero converted tumors showed worse overall survival compared with those with HER2-low concordant tumors. In conclusion, HER2 status changes during breast cancer progression in significant proportions, mostly between zero and low status. As HER2 instability increases during progression and affects clinical outcome, HER2 status needs to be reevaluated in recurrent settings.
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Neoplasias da Mama , Progressão da Doença , Recidiva Local de Neoplasia , Receptor ErbB-2 , Humanos , Receptor ErbB-2/metabolismo , Feminino , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Adulto , Idoso , Recidiva Local de Neoplasia/metabolismo , Biomarcadores Tumorais/metabolismo , Idoso de 80 Anos ou maisRESUMO
Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected. We now report Red2Flpe-SCON: a mosaic knockout system that uses multicolor reporters to label both mutant and wild-type cells. We develop the Red2Flpe mouse line for red clone-specific Flpe expression, as well as the FRT-based SCON (Short Conditional IntrON) method to facilitate tunable conditional mosaic knockouts in mice. We use the Red2Flpe-SCON method to study Sox2 mutant clonal analysis in the esophageal epithelium of adult mice which reveal that the stem cell gene, Sox2, is less essential for adult stem cell maintenance itself, but rather for stem cell proliferation and differentiation.
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Proteínas Luminescentes , Camundongos Knockout , Proteína Vermelha Fluorescente , Fatores de Transcrição SOXB1 , Animais , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Camundongos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mosaicismo , Diferenciação Celular , Proliferação de Células/genética , Esôfago/metabolismo , Esôfago/patologia , Linhagem da Célula/genética , Íntrons/genética , Feminino , MasculinoRESUMO
COVID-19-motivated social distancing made online concerts common practice in 2020 and 2021, with millions logging into streaming sites to see their favorite artists perform in realtime. For some fans, watching alone at home may have been enough, but concert-concurrent surges of social media activity suggest many virtual performance attendees are doing more. To understand why fans would turn their attention from these precious performance streams to social media, we explored Twitter engagement during four live streamed concerts performed by the Kpop group BTS in 2021. In public Tweets sampled by either concert hashtag or a predefined stream of users and keywords, we evaluated patterns in posting rates in relation to concert program events and investigated the content patterns in 1,200 Tweets sampled from four ranges of popularity (number of Retweets during the concert). Across concerts, short "Shout" Tweets surged at the start of songs, while the rate of retweets often fell during musical performances and shot up when BTS was off stage. Content analysis on the subsample found the materials most widely shared were informational or featured concert visuals, mimicking how fans use their phones at in-person concerts. Most original posts received few Retweets and were more personal and expressive of admiration for the performers. Comparison between the samples (concert hashtag vs. stream) also suggests users were strategic in using or omitting official concert hashtags with the strongest differences in the most widely disseminated content. Postings on Twitter during these performances seemed principally directed to fellow fans and audience members, by individuals choosing to share their own excitement and check in with others. By leveraging their existing social media networks, these concert attendees constructed a collective and interactive concert space, connecting with friends and strangers in the crowd and helping each other capture a richer experience than any broadcasting platform currently supports.
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As the biopharmaceutical industry continues to mature in its cost-effectiveness and productivity, many companies have begun employing larger-scale biomanufacturing and bioprocessing protocols. While many of these protocols require cells with anchorage-independent growth, it remains challenging to induce the necessary suspension adaptations in many different cell types. In addition, although transfection efficiency is an important consideration for all cells, especially for therapeutic protein production, cells in suspension are generally more difficult to transfect than adherent cells. Thus, much of the biomanufacturing industry is focused on the development of new human cell lines with properties that can support more efficient biopharmaceutical production. With this in mind, we identified a set of "Adherent-to-Suspension Transition" (AST) factors, IKZF1, BTG2 and KLF1, the expression of which induces adherent cells to acquire anchorage-independent growth. Working from the HEK293A cell line, we established 293-AST cells and 293-AST-TetR cells for inducible and reversible reprogramming of anchorage dependency. Surprisingly, we found that the AST-TetR system induces the necessary suspension adaptations with an accompanying increase in transfection efficiency and protein expression rate. Our AST-TetR system therefore represents a novel technological platform for the development of cell lines used for generating therapeutic proteins.
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Proteínas Recombinantes , Humanos , Células HEK293 , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Adesão Celular/genética , Transfecção/métodos , Técnicas de Cultura de Células/métodosRESUMO
PURPOSE: This study investigated the relationship between allergic diseases, general anxiety disorder, and depressive symptoms among Korean adolescents. METHODS: A secondary analysis was conducted on the findings of the 18th Korea Youth Risk Behavior Survey (2022). The study included 51,850 adolescents and analyzed the relationships among allergic diseases, general anxiety disorder, and depressive symptoms using complex samples logistic regression analysis. RESULTS: Among the Korean adolescents, 12.7% experienced general anxiety disorder, while 28.7% experienced depressive symptoms. The prevalence of allergic diseases was 5.7% for asthma, 36.3% for allergic rhinitis, and 22.2% for atopic dermatitis. General anxiety disorder was associated with asthma and allergic rhinitis but not atopic dermatitis. Depressive symptoms were associated asthma, allergic rhinitis, and atopic dermatitis. CONCLUSION: Examining the correlation among allergic diseases, general anxiety disorder, and depressive symptoms in adolescents underscores the need for implementing suitable strategies. Moreover, when addressing general anxiety disorder and depressive symptoms in adolescents, it becomes crucial to consider the presence of allergic diseases.
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Efficient photovoltaic devices must be efficient light emitters to reach the thermodynamic efficiency limit. Here, we present a promising prospect of perovskite photovoltaics as bright emitters by harnessing the significant benefits of photon recycling, which can be practically achieved by suppressing interfacial quenching. We have achieved radiative and stable perovskite photovoltaic devices by the design of a multiple quantum well structure with long (â¼3 nm) organic spacers with oleylammonium molecules at perovskite top interfaces. Our L-site exchange process (L: barrier molecule cation) enables the formation of stable interfacial structures with moderate conductivity despite the thick barriers. Compared to popular short (â¼1 nm) Ls, our approach results in enhanced radiation efficiency through the recursive process of photon recycling. This leads to the realization of radiative perovskite photovoltaics with both high photovoltaic efficiency (in-lab 26.0%, certified to 25.2%) and electroluminescence quantum efficiency (19.7 % at peak, 17.8% at 1-sun equivalent condition). Furthermore, the stable crystallinity of oleylammonium-based quantum wells enables our devices to maintain high efficiencies for over 1000 h of operation and >2 years of storage.
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The elucidation of the pathophysiology underlying various diseases necessitates the development of research platforms that faithfully mimic in vivo conditions. Traditional model systems such as two-dimensional cell cultures and animal models have proven inadequate in capturing the complexities of human disease modeling. However, recent strides in organoid culture systems have opened up new avenues for comprehending gastric stem cell homeostasis and associated diseases, notably gastric cancer. Given the significance of gastric cancer, a thorough understanding of its pathophysiology and molecular underpinnings is imperative. To this end, the utilization of patient-derived organoid libraries emerges as a remarkable platform, as it faithfully mirrors patient-specific characteristics, including mutation profiles and drug sensitivities. Furthermore, genetic manipulation of gastric organoids facilitates the exploration of molecular mechanisms underlying gastric cancer development. This review provides a comprehensive overview of recent advancements in various adult stem cell-derived gastric organoid models and their diverse applications.
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PURPOSE: The tumor immune microenvironment can change after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC). We aimed to investigate the effects of NAC on PD-L1 (SP142) status and its clinical significance in TNBC. METHODS: Paired samples of biopsy and resection specimens were collected from 182 patients with TNBC before and after NAC. PD-L1 (SP142) expression in immune cells in pre- and post-NAC breast cancer samples and the changes between them were analyzed, along with their relationships with the clinicopathological features and clinical outcomes of the patients. RESULTS: Of the 182 patients, 61 (33.5%) achieved pathologic complete response (pCR) after NAC. PD-L1 (SP142) positivity, defined as immune cell staining in ≥ 1% of tumor area, was a predictor for pCR. PD-L1-positive immune cells significantly increased after NAC (2.8% to 5.2% on average) in 109 patients with measurable residual disease. Alteration of PD-L1 status was observed in 24 (22.0%) of the 109 patients with measurable residual tumors after NAC, and all PD-L1 status-converted patients, except one, revealed negative-to-positive conversion. Regarding chemotherapeutic agents, the use of platinum agents was associated with a significant increase in PD-L1-positive immune cells after NAC. In survival analyses, a positive PD-L1 status after NAC and increase of PD-L1-positive immune cells after NAC were associated with better recurrence-free survival of the patients. CONCLUSION: PD-L1 (SP142) status changes after NAC, mostly as a positive conversion. As PD-L1 (SP142) status can convey prognostic and predictive information, it needs to be tested before and after NAC.
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Antígeno B7-H1 , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Antígeno B7-H1/metabolismo , Feminino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Quimioterapia Adjuvante/métodos , Estadiamento de Neoplasias , Relevância ClínicaRESUMO
The anticancer therapeutic effects of usnic acid (UA), a lichen secondary metabolite, have been demonstrated in vitro and in vivo. However, the mechanism underlying the anticancer effect of UA remains to be clarified. In this study, the target protein of UA was identified using a UA-linker-Affi-Gel molecule, which showed that UA binds to the 14-3-3 protein. UA binds to 14-3-3, causing the degradation of proteasomal and autophagosomal proteins. The interaction of UA with 14-3-3 isoforms modulated cell invasion, cell cycle progression, aerobic glycolysis, mitochondrial biogenesis, and the Akt/mTOR, JNK, STAT3, NF-κB, and AP-1 signaling pathways in colorectal cancer. A peptide inhibitor of 14-3-3 blocked or regressed the activity of UA and inhibited its effects. The results suggest that UA binds to 14-3-3 isoforms and suppresses cancer progression by affecting 14-3-3 targets and phosphorylated proteins.
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COVID-19 has made working from home routine for many. People who have had to maintain their productivity, particularly in physically and/or socially unacceptable home-working situations, experienced one of the pandemic's disadvantages. The experience can vary substantially among individuals as well as by country. This study presents the results of a comparative study of the Netherlands and Korea. Working from home was not uncommon in the Netherlands before the pandemic; however, in Korea, employers adopted working from home from its start, and that increased rapidly. An online survey enabled us to compare the physical and social conditions of current home workspaces in both countries, to understand how well-equipped they were to support people who had to work from home. We studied the changes in productivity and physical/mental health before and during COVID-19, to learn how people coped with working from home in both countries. Contrary to expectations, Koreans showed better scores than people in the Netherlands, in terms of changes in health and productivity. This article discusses various aspects of that result, such as satisfaction with home workspace, housing type, job position and prior experience, compulsoriness, and frequency of working from home. Relieving stress and concentration appeared to be the most important dimensions of telecommuters' satisfaction with working from home environments in both countries. The results are the basis for suggesting the development of strategies for a desirable WFH environment, considering different background contexts, experiences and cultures.
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COVID-19 , Pandemias , Humanos , Países Baixos/epidemiologia , COVID-19/epidemiologia , República da Coreia/epidemiologia , Capacidades de EnfrentamentoRESUMO
BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low status has recently gained attention because of the potential therapeutic benefits of antibody-drug conjugates (ADCs) in breast cancer patients. We aimed to investigate the concordance of HER2 status between core needle biopsy (CNB) and subsequent surgical resection specimens focusing on the HER2-low status. METHODS: This retrospective study was conducted in 1,387 patients with invasive breast cancer whose HER2 status was evaluated in both CNB and surgical resection specimens. The discordance rates between CNB and surgical resection specimens and the clinicopathological features associated with HER2 status discordance were analyzed. RESULTS: The overall concordance rates of HER2 status between CNB and surgical resection specimens were 99.0% (κ = 0.925) for two-group classification (negative vs. positive) and 78.5% (κ = 0.587) for three-group classification (zero vs. low vs. positive). The largest discordance occurred in CNB-HER2-zero cases with 42.8% of them reclassified as HER2-low in surgical resection. HER2 discordance was associated with lower histologic grade, tumor multiplicity, and luminal A subtype. In multivariate analysis, tumor multiplicity and estrogen receptor (ER) positivity were independent predictive factors for HER2-zero to low conversion. CONCLUSIONS: Incorporation of HER2-low category in HER2 status interpretation reduces the concordance rate between CNB and surgical resection specimens. Tumor multiplicity and ER positivity are predictive factors for conversion from HER2-zero to HER2-low status. Therefore, HER2 status should be re-evaluated in resection specimens when considering ADCs in tumors exhibiting multiplicity and ER positivity.
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Neoplasias da Mama , Receptor ErbB-2 , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Feminino , Biópsia com Agulha de Grande Calibre , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Receptores de Estrogênio/metabolismoRESUMO
Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.
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Myocardial infarction (MI) is a common cardiovascular disease, the early diagnosis of which is essential for effective treatment and reduced mortality. Therefore, novel methods are required for automatic screening or early diagnosis of MI, and many studies have proposed diverse conventional methods for its detection. In this study, we aimed to develop a sleep-myocardial infarction (sleepMI) algorithm for automatic screening of MI based on nocturnal electrocardiography (ECG) findings from diagnostic polysomnography (PSG) data using artificial intelligence (AI) models. The proposed sleepMI algorithm was designed using representation and ensemble learning methods and optimized via dropout and batch normalization. In the sleepMI algorithm, a deep convolutional neural network and light gradient boost machine (LightGBM) models were mixed to obtain robust and stable performance for screening MI from nocturnal ECG findings. The nocturnal ECG signal was extracted from 2,691 participants (2,331 healthy individuals and 360 patients with MI) from the PSG data of the second follow-up stage of the Sleep Heart Health Study. The nocturnal ECG signal was extracted 3 h after sleep onset and segmented at 30-s intervals for each participant. All ECG datasets were divided into training, validation, and test sets consisting of 574,729, 143,683, and 718,412 segments, respectively. The proposed sleepMI model exhibited very high performance with precision, recall, and F1-score of 99.38%, 99.38%, and 99.38%, respectively. The total mean accuracy for automatic screening of MI using a nocturnal single-lead ECG was 99.387%. MI events can be detected using conventional 12-lead ECG signals and polysomnographic ECG recordings using our model.
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This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.
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Neoplasias Pulmonares , Nanopartículas Metálicas , Humanos , Raios X , Ouro/farmacologia , Simulação por Computador , Método de Monte CarloRESUMO
(1) Background: Unruptured intracranial aneurysm (UIA) occurs in 1-2% of the population and is being increasingly detected. Patients with UIA are treated with close observation, endovascular coiling or surgical clipping. The proportion of endovascular coiling has been rising. However, complications such as cerebral infarction (CI), intracranial hemorrhage (ICRH), and death remain crucial issues after coil treatment. (2) Methods: We analyzed the incidence and risk factors of complications after the use of coil in patients with UIA based on the patients' characteristics. We utilized the Health Insurance Review and Assessment (HIRA) database. Patients treated with coils for UIA between 1 January 2015 and 1 December 2021 were retrospectively analyzed. (3) Results: Of the total 35,140 patients, 1062 developed ICRH, of whom 87 died, with a mortality rate of 8.2%. Meanwhile, 749 patients developed CI, of whom 29 died, with a mortality rate of 3.9%. The overall mortality rate was 1.8%. In a univariate analysis of the risk factors, older age, males, a higher Charlson Comorbidity Index (CCI) score, and diabetes increase the risk of CI. Meanwhile, males with higher CCI scores and hemiplegia or paraplegia show increased ICRH risk. Older age, males and metastatic solid tumors relate to increased mortality risk. (4) Conclusions: This study is significant in that the complications based on the patient's underlying medical condition were analyzed.