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In recent years, visible light-induced reactions of diazo compounds have attracted increasing attention in organic synthesis, leading to improvement of existing reactions, as well as to the discovery of unprecedented transformations. Thus, photochemical or photocatalytic generation of both carbenes and radicals provide milder tools toward these key intermediates for many valuable transformations. However, the vast majority of the transformations represent new reactivity modes of diazo compounds, which are achieved by the photochemical decomposition of diazo compounds and photoredox catalysis. In particular, the use of a redox-active photocatalysts opens the avenue to a plethora of radical reactions. The application of these methods to diazo compounds led to discovery of transformations inaccessible by the classical reactivity associated with carbenes and metal carbenes. In most cases, diazo compounds act as radical sources but can also serve as radical acceptors. Importantly, the described processes operate under mild, practical conditions. This Review describes this subfield of diazo compound chemistry, particularly focusing on recent advancements.
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Reactive oxygen species (ROS) induces necroptotic and ferroptosis in melanoma cells. Salidroside (SAL) regulates ROS in normal cells and inhibits melanoma cell proliferation. This study used human malignant melanoma cells treated with SAL either alone or in combination with ROS scavenger (NAC) or ferroptosis inducer (Erastin). Through cell viability, wound healing assays, and a Seahorse analyze found that SAL inhibited cell proliferation, migration, extracellular acidification rate, and oxygen consumption rate. Metabolic flux analysis, complexes I, II, III, and IV activity of the mitochondrial respiratory chain assays, mitochondrial membrane potential assay, mitochondrial ROS, and transmission electron microscope revealed that SAL induced mitochondrial dysfunction and ultrastructural damage. Assessment of malondialdehyde, lipid ROS, iron content measurement, and Western blot analysis showed that SAL activated lipid peroxidation and promoted ferroptosis in A-375 cells. These effects were abolished after NAC treatment. Additionally, SAL and Erastin both inhibited cell proliferation and promoted cell death; SAL increased the Erastin sensitivity of cells while NAC antagonized it. In xenograft mice, SAL inhibited melanoma growth and promoted ROS-dependent ferroptosis. SAL induced mitochondrial dysfunction and ferroptosis to block melanoma progression through ROS production, which offers a scientific foundation for conducting SAL pharmacological research in the management of melanoma.
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Proliferación Celular , Ferroptosis , Glucósidos , Melanoma , Mitocondrias , Fenoles , Especies Reactivas de Oxígeno , Ferroptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Humanos , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Melanoma/patología , Fenoles/farmacología , Glucósidos/farmacología , Animales , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proliferación Celular/efectos de los fármacos , Ratones , Línea Celular Tumoral , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacosRESUMEN
High-throughput synthesis and screening of chemical libraries play pivotal roles in drug discovery. Click chemistry has emerged as a powerful strategy for constructing highly modular chemical libraries. However, the development of new click reactions and unlocking new clickable building blocks remain exceedingly challenging. Herein, we describe a double-click strategy that enables the sequential ligations of widely available carboxylic acids and amines with fluorosulfuryl isocyanate (FSO2NCO) via a modular amidation/SuFEx (sulfur-fluoride exchange) process. This method provides facile access to chemical libraries of N-fluorosulfonyl amides (RCONHSO2F) and N-acylsulfamides (RCONHSO2NR'R'') in near-quantitative yields under simple and practical conditions. The robustness and efficiency of this double click strategy is showcased by the facile construction of chemical libraries in 96-well microtiter plates from a large number of carboxylic acids and amines. Preliminary biological activity screening reveals that some compounds exhibit high antimicrobial activities against Gram-positive bacterium S. aureus and drug-resistant MRSA (MIC up to 6.25â µg â mL-1). These results provide compelling evidence for the potential application of modular click chemistry library as an enabling technology in high-throughput medicinal chemistry.
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Rosacea is a chronic inflammatory skin disease whose late manifestations have not yet been clearly reported in animal models. The objective of this study is to describe the skin lesions and major histopathological changes in a rosacea-like phenotype in mice induced by prolonged LL-37 administration and furthermore, to assess the potential of long-term LL-37 administration in inducing irreversible rosacea-like skin lesion models. Balb/c mice were continuously injected intradermally with LL-37 every 12 h to induce a rosacea-like phenotype. After LL-37 injections were administered for 20 consecutive days, the area of rosacea-like lesions gradually expanded in the first 13 days, then entered a stable phase. Haematoxylin and eosin (H&E) and Van Gieson's staining showed a high degree of inflammatory cell aggregation, thickening of the epidermis and dermis, and collagen deposition in large quantities. The results of immunofluorescence staining and Western blotting showed that the expression of α-SMA, TNF-α, vimentin, and COL1 in the skin of mice was significantly upregulated. Short-term LL-37 administration induced rosacea-like lesions that only featured the aggregation of inflammatory factors and thickening of the epidermis, whereas no collagen hyperplasia was observed, and a full recovery was noticed. However, rosacea-like skin lesions induced by long-term LL-37 administration did not completely recover. Our study compares rosacea-like lesions induced by short-term versus long-term LL-37 administration, and the results suggest that irreversible rosacea-like lesions can be induced by long-term LL-37 administration.
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BACKGROUND: NOTCH mutations (NOTCHmut ) are recognized as major oncogenic drivers associated with controversial clinical impact on T-cell acute lymphoblastic leukemia (T-ALL), whereas their clinical value on acute myeloid leukemia (AML) is poorly defined. METHODS: A study involving 878 consecutive newly diagnosed patients with AML was undertaken in an institution with available clinical data to unravel the impact of NOTCHmut on prognosis. RESULTS: In the study, NOTCHmut were discovered in 3.6% (32/878) of included patients with AML and composed substitution-missense, frameshift mutation, substitution-nonsense, and insertion-in frame. These mutations were more commonly associated with low platelet (29 vs 42 × 109 /L, p = .024) count and coexisted with BCOR/BCORL1 (15.6% vs 3.2%, p = .001), DNMT3A (28.1% vs 12.5%, p = .021), and MPL (9.4% vs 0.8%, p = .004) mutations compared with NOTCH wild-type (NOTCHwt ). No significant difference was observed in treatment responses between NOTCHmut and NOTCHwt . The presence of NOTCHmut was associated with worse overall survival ([OS], 1 year-OS: 68.0% vs 84.2%; 3 year-OS: 48.3% vs 59.6%; p = .059) and relapse-free survival ([RFS], 1 year-RFS: 78.3% vs 85.4%; 3 year-RFS: 54.5% vs 76.9%; p = .018), especially within the European Leukemia Net 2017 intermediate-risk group. Furthermore, allogeneic hematopoietic stem cell transplantation might abrogate the dismal impact of NOTCHmut on RFS. In multivariate analysis, NOTCHmut were found to be an independent factor negatively influencing RFS (hazard ratio, 2.153; 95% CI, 1.166-3.975; p = .014). CONCLUSION: This study suggests that NOTCHmut may serve as an indicator for poor prognosis of AML. PLAIN LANGUAGE SUMMARY: Although NOTCH mutations (NOTCHmut ) are well studied in T-cell acute lymphoblastic leukemia (T-ALL), less is known about their incidence and prognostic implications in acute myeloid leukemia (AML). A total of 878 newly diagnosed patients with AML was retrospectively analyzed; it was found that the frequency of NOTCHmut was relatively low but was associated with an adverse prognosis.
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Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Estudios Retrospectivos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutación , PronósticoRESUMEN
A novel metal-organic framework (MOF)-on-MOF dual enzyme-mimic nanozyme was designed as enhanced cascade signal amplification for the colorimetric and chemiluminescent (CL) dual-mode aptasensing. The MOF-on-MOF hybrid is composed of MOF-818 with catechol oxidase-like activity and iron porphyrin MOF [PMOF(Fe)] with peroxidase-like activity, called MOF-818@PMOF(Fe). MOF-818 can catalyze the 3,5-di-tert-butylcatechol substrate and produce H2O2 in situ. Subsequently, PMOF(Fe) catalyzes H2O2 to produce reactive oxygen species, which oxidize 3,3',5,5'-tetramethylbenzidine or luminol to produce color or luminescence. Thanks to the nano-proximity effect and the confinement effect, the efficiency of the biomimetic cascade catalysis is greatly improved, which in turn generates enhanced colorimetric and CL signals. Taking the detection of chlopyrifos as an example, the prepared dual enzyme-mimic MOF nanozyme is combined with the aptamer with specific recognition ability to develop a colorimetric/CL dual-mode aptasensor for highly sensitive and selective detection of chlorpyrifos. The proposed MOF-on-MOF dual nanozyme-enhanced cascade system may provide a new pathway for the further development of a biomimetic cascade sensing platform.
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Estructuras Metalorgánicas , Colorimetría , Peróxido de Hidrógeno , Peroxidasas/metabolismo , CatálisisRESUMEN
Conditioning therapy is an essential procedure prior to hematopoietic stem cell transplant (HSCT), imposing a great impact on the outcomes of recipients. We performed a prospective randomized controlled trial to assess the outcome of HSCT recipients with myeloid malignancies after receiving the conditioning therapy consisting of modified BUCY (mBUCY), N-acetyl-L-cysteine (NAC), and decitabine. Enrolled patients were randomly allocated to either Arm A (decitabine, day -12 to -10; NAC, day -9 to +30; mBUCY, day -9 to -2), or Arm B (mBUCY regimen followed by stem cells infusion). Seventy-six patients in Arm A and 78 patients in Arm B were finally evaluated. The results showed platelet recovery accelerate in Arm A, with more patients achieving a platelet count of ≥50 × 109 /L than Arm B at day +30 and +60 (p = .004 and .043, respectively). The cumulative incidence of relapse is 11.8% (95% CI 0.06-0.22) in Arm A, and 24.4% (95% CI 0.16-0.35) in Arm B (p = .048). The estimated 3-year overall survival rate was 86.4% (±4.4%) and 79.9% (±4.7%) in 2 arms, respectively (p = .155). EFS at 3 years was 79.2% (±4.9%) in Arm A and 60.0% (±5.9%) in Arm B (p = .007). Intracellular reactive oxygen species (ROS) level was found to be reversely correlated with platelet recovery, and fewer patients in Arm A displayed excessive ROS within hematopoietic progenitor cells compared to Arm B. In conclusion, the addition of decitabine and NAC to mBUCY is a feasible and promising conditioning therapy for myeloid malignancies patients.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trastornos Mieloproliferativos , Neoplasias , Humanos , Decitabina , Acetilcisteína/uso terapéutico , Busulfano , Estudios Prospectivos , Especies Reactivas de Oxígeno , Trastornos Mieloproliferativos/complicaciones , Trasplante de Células Madre Hematopoyéticas/métodos , Terapia Conductista , Neoplasias/complicaciones , Acondicionamiento Pretrasplante/efectos adversos , Leucemia Mieloide Aguda/terapia , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Regulatory variants in gene expression serve as bridges linking genetic variation and phenotypic plasticity. Environmental conditions typically influence the effects of regulatory variants on phenotypic plasticity; however, such genotype-by-environment interactions (G × E) are poorly understood. This study aimed to investigate the genetic basis of G × E in estuarine oyster (Crassostrea ariakensis), which is an important model animal for studying environmental adaption owing to its high plasticity and large intraspecific divergence. Genome-wide mapping of expression quantitative trait loci (eQTLs) for 23 environmental adaptive genes was performed for 256 estuarine oysters. We identified 1194 eQTL single nucleotide polymorphisms (eSNPs), including 433 cis-eSNPs in four genes and 722 trans-eSNPs in eight genes. The expression variation explanation of cis-eSNPs (9.95%) was significantly higher than that of trans-eSNPs (9.15%). We specifically showed cis- and trans-eSNPs with high linkage disequilibrium (LD) for Traf7, Slc6a5, Ggt, and Dap3. For example, we identified a cis-regulatory LD block containing 68 cis-eSNP and a trans-regulatory LD block, including 20 trans-eSNPs in Traf7. A high proportion (85%) of 40 vital eSNPs exhibited significant G × E effects. We identified crossing and nonparallel interactions of G × E, with the tag cis-eSNPs of Baat and Slc6a5 as representatives. Our results indicated that cis-eQTLs are highly conserved. This study provides insights into the understanding of adaptive evolutionary mechanisms and phenotypic response prediction to variable environments, as well as the genetic improvement for superior adaptive traits for genetic resource conservation and aquaculture.
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Bacillus subtilis as microbial fertilizers contribute to avoiding the harmful effects of traditional agricultural fertilizers and pesticides. However, there are many restrictions on the practical application of fertilizers. In this study, microbial biochar formulations (BCMs) were prepared by loading biochar with B. subtilis SL-44. Pot experiments were conducted to evaluate the effects of the BCMs on soil fertility, Fusarium wilt control, and radish plant growth. The application of BCMs dramatically improved soil properties and favored plant growth. Compared with SL-44 and biochar treatments, the BCMs treatments increased radish plant physical-chemical properties and activities of several enzymes in the soil. What's more, Fusarium wilt incidence had decreased by 59.88%. In addition, the BCMs treatments exhibited a significant increase in the abundance of bacterial genera in the rhizosphere soil of radish. Therefore, this study demonstrated that BCMs may be an eco-friendly strategy for improving soil fertility, reducing Fusarium wilt, and promoting radish plant growth.
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Fusarium , Raphanus , Suelo/química , Bacillus subtilis , Fertilizantes/análisis , Microbiología del Suelo , RizosferaRESUMEN
OBJECTIVE: To establish a scientific foundation for focused stroke prevention and treatment efforts by comprehending the risk variables connected to carotid plaque formation in adults over 40 who are at high risk of stroke in Yubei District, Chongqing, China. METHODS: By comparing the differences in carotid plaque formation between people of different ages, smoking, blood pressure levels, low-density lipoprotein levels, and glycosylated hemoglobin levels, questionnaires and physical exams were performed on a random sample of permanent residents aged 40 years in three communities in Yubei District, Chongqing, China. The goal was to investigate the risk factors associated with carotid plaque formation in the population. RESULTS: The incidence of carotid plaque gradually increased in the study population as age, blood pressure, low-density lipoprotein, and glycosylated hemoglobin levels increased. The difference in carotid plaque formation between people of different ages, smoking, blood pressure levels, low-density lipoprotein levels, and glycosylated hemoglobin levels was statistically significant (p<0.05). The findings of the multifactorial logistic regression analysis revealed that there was a tendency for the risk of developing carotid plaque to rise with age; the risk of developing carotid plaque in hypertensive patients was (OR=1.41,95% CI: 1.03-1.93); the population of smokers was (OR=2.01,95%CI:1.33-3.05); the low-density lipoprotein cholesterol borderline increased group was (OR=1.94,95%CI:1.03-3.66); the low-density lipoprotein cholesterol elevated group was (OR=2.71,95%CI: 1.26-5.84); glycosylated hemoglobin elevated group was (OR=1.40,95%CI: 1.01-1.94) (p<0.05). CONCLUSION: Age, smoking, blood pressure, low-density lipoprotein, and glycosylated hemoglobin are all associated with carotid plaque formation in those over 40 who are at high risk of stroke. As a result, health education for residents needs to be strengthened to raise knowledge of carotid plaque prevention.
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Placa Aterosclerótica , Accidente Cerebrovascular , Adulto , Humanos , Hemoglobina Glucada , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Factores de Riesgo , Placa Aterosclerótica/epidemiología , Colesterol , LDL-Colesterol , China/epidemiologíaRESUMEN
In recent years, laser engraving has received widespread attention as a convenient, efficient, and programmable method which has enabled high-quality porous graphene to be obtained from various precursors. Laser engraving is often used to fabricate the dielectric layer with a microstructure for capacitive pressure sensors; however, the usual choice of electrodes remains poorly flexible metal electrodes, which greatly limit the overall flexibility of the sensors. In this work, we propose a flexible capacitive pressure sensor made entirely of thermoplastic polyurethane (TPU) and laser-induced graphene (LIG) derived from wood. The capacitive pressure sensor consisted of a flexible LIG/TPU electrode (LTE), an LIG/TPU electrode with a microhole array, and a dielectric layer of TPU with microcone array molded from a laser-engraved hole array on wood, which provided high sensitivity (0.11 kPa-1), an ultrawide pressure detection range (20 Pa to 1.4 MPa), a fast response (~300 ms), and good stability (>4000 cycles, at 0-35 kPa). We believe that our research makes a significant contribution to the literature, because the easy availability of the materials derived from wood and the overall consistent flexibility meet the requirements of flexible electronic devices.
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Palladium hydrides are traditionally employed in hydrofunctionalization (i.e. monofunctionalization) of conjugated dienes and enynes, owning to its facile protic hydropalladation of electron-rich (or neutral) unsaturated bonds. Herein, we report a mild PdH-catalyzed difunctionalization of conjugated dienes and enynes. This protocol is enabled by the chemoselectivity switch of the initial hydropalladation step achieved by visible light enhancement of hydricity of PdH species. This method allows for cascade annulation of dienes and enynes with various easily available and abundant substrates, such as acrylic acids, acrylic amides, and Baylis-Hillman adducts, toward a wide range of alkenyl or alkynyl lactones, lactams, and tetrahydrofurans. This protocol also provides an easy access to complex spiro-fused tricyclic frameworks.
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We report the first palladium hydride enabled hydroalkenylation of strained molecules. This new mild protocol proceeds via a regio- and chemoselective hydropalladation step, followed by a photoinduced radical alkyl Heck reaction. This methodology represents a new reactivity mode for strained molecules and opens new avenues for photoinduced palladium catalysis. The reaction is compatible with a wide range of functional groups and can be applied to complex structures, delivering a diverse array of highly valuable and modifiable alkenylated cyclobutanes and cyclopropanes. A hydroalkenylation/diastereoselective rearrangement cascade toward a cyclopentene scaffold has also been demonstrated.
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Ciclobutanos , Paladio , Paladio/química , Estereoisomerismo , CatálisisRESUMEN
Superhard materials are among the most scarce functional inorganic solids in existence. Indeed, recent research suggested that less than 0.1% of all known materials are likely to have a Vickers hardness ≥40 GPa. Here, an anomaly detection framework is created to treat these materials as rare occurrences by encoding and reconstructing the input composition and crystal structure information without supervision. The resulting model can quantitatively identify outliers from "normal" behaving materials, leading to the discovery of materials with exceptional properties such as a superhard response. Moreover, examining the difference between the encoded and decoded crystal structure provides fundamental insights into the crystal-chemical origin of hardness. The presented methodology is ultimately generalizable, enabling the design of other outlier materials with rare and unexpected physical properties.
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Dureza , Compuestos InorgánicosRESUMEN
Genetic variation and phenotypic plasticity are both important to adaptive evolution. However, how they act together on particular traits remains poorly understood. Here, we integrated phenotypic, genomic, and transcriptomic data from two allopatric but closely related congeneric oyster species, Crassostrea angulata from southern/warm environments and Crassostrea gigas from northern/cold environments, to investigate the roles of genetic divergence and plasticity in thermal adaptation. Reciprocal transplantation experiments showed that both species had higher fitness in their native habitats than in nonnative environments, indicating strong adaptive divergence. The southern species evolved higher transcriptional plasticity, and the plasticity was adaptive, suggesting that increased plasticity is important for thermal adaptation to warm climates. Genome-wide comparisons between the two species revealed that genes under selection tended to respond to environmental changes and showed higher sequence divergence in noncoding regions. All genes under selection and related to energy metabolism exhibited habitat-specific expression with genes involved in ATP production and lipid catabolism highly expressed in warm/southern habitats, and genes involved in ATP consumption and lipid synthesis were highly expressed in cold/northern habitats. The gene for acyl-CoA desaturase, a key enzyme for lipid synthesis, showed strong selective sweep in the upstream noncoding region and lower transcription in the southern species. These results were further supported by the lower free fatty acid (FFA) but higher ATP content in southern species and habitat, pointing to significance of ATP/FFA trade-off. Our findings provide evidence that noncoding variation and transcriptional plasticity play important roles in shaping energy metabolism for thermal adaptation in oysters.
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Crassostrea , Aclimatación/genética , Adaptación Fisiológica/genética , Animales , Crassostrea/genética , Metabolismo Energético/genética , GenomaRESUMEN
BACKGROUND: Interleukin (IL)-7 signaling through CD127 is impaired in lymphocytes in cancers and chronic infections, resulting in CD8+ T cell exhaustion. The mechanisms underlying CD8+ T cell responses to IL-7 in melanoma remain not completely elucidated. We previously showed reduced IL-7 level in melanoma patients. Thus, the aim of this study was to investigate the effect of IL-7 regulation on CD127 expression and CD8+ T cell responses in melanoma. METHODS: Healthy controls and primary cutaneous melanoma patients were enrolled. Membrane-bound CD127 (mCD127) expression on CD8+ T cells was determined by flow cytometry. Soluble CD127 (sCD127) protein level was measured by ELISA. Total CD127 and sCD127 mRNA level was measured by real-time PCR. CD8+ T cells were stimulated with recombinant human IL-7, along with signaling pathway inhibitors. CD8+ T cells were co-cultured with melanoma cell line, and the cytotoxicity of CD8+ T cells was assessed by measurement of lactate dehydrogenase expression. RESULTS: Plasma sCD127 was lower in melanoma patients compared with controls. The percentage of CD8+ T cells expressing mCD127 was higher, while sCD127 mRNA level was lower in peripheral and tumor-infiltrating CD8+ T cells from melanoma patients. There was no significant difference of total CD127 mRNA expression in CD8+ T cells between groups. IL-7 stimulation enhanced total CD127 and sCD127 mRNA expression and sCD127 release by CD8+ T cells. However, mCD127 mRNA expression on CD8+ T cells was not affected. This process was mainly mediated by phosphatidylinositol 3-kinase (PI3K) pathway. CD8+ T cells from melanoma patients exhibited decreased cytotoxicity. IL-7 stimulation promoted CD8+ T cell cytotoxicity, while inhibition of PI3K dampened IL-7-induced elevation of CD8+ T cell cytotoxicity. CONCLUSION: The current data suggested that insufficient IL-7 secretion might contribute to CD8+ T cell exhaustion and CD127 dysregulation in patients with primary cutaneous melanoma.
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Subunidad alfa del Receptor de Interleucina-7/metabolismo , Melanoma , Neoplasias Cutáneas , Linfocitos T CD8-positivos , Humanos , Interleucina-7/metabolismo , Melanoma/metabolismo , Fosfatidilinositol 3-Quinasas , ARN Mensajero/metabolismo , Neoplasias Cutáneas/metabolismo , Melanoma Cutáneo MalignoRESUMEN
Previous studies on deep learning (DL) applications in pathology have focused on pathologist-versus-algorithm comparisons. However, DL will not replace the breadth and contextual knowledge of pathologists; rather, only through their combination may the benefits of DL be achieved. A fully crossed multireader multicase study was conducted to evaluate DL assistance with pathologists' diagnosis of gastric cancer. A total of 110 whole-slide images (WSI) (50 malignant and 60 benign) were interpreted by 16 board-certified pathologists with or without DL assistance, with a washout period between sessions. DL-assisted pathologists achieved a higher area under receiver operating characteristic curve (ROC-AUC) (0.911 vs. 0.863, P = 0.003) than unassisted in interpreting the 110 WSIs. Pathologists with DL assistance demonstrated higher sensitivity in detection of gastric cancer than without (90.63% vs. 82.75%, P = 0.010). No significant difference was observed in specificity with or without deep learning assistance (78.23% vs. 79.90%, P = 0.468). The average review time per WSI was shortened with DL assistance than without (22.68 vs. 26.37 second, P = 0.033). Our results demonstrated that DL assistance indeed improved pathologists' accuracy and efficiency in gastric cancer diagnosis and further boosted the acceptance of this new technique.
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Aprendizaje Profundo , Neoplasias Gástricas , Algoritmos , Humanos , Patólogos , Curva ROC , Neoplasias Gástricas/diagnósticoRESUMEN
Allogeneic hematopoietic stem cell transplantation is the only curative therapy for patients with myelodysplastic syndrome. Transplantation-associated thrombotic microangiopathy (TA-TMA) remains a cause of death after transplantation. This study assessed the risk factors of TA-TMA and established a prediction model for this complication. We launched a real-world study from 303 MDS patients after allo-HSCT from Dec 1, 2007, to Jun 1, 2018. Logistic regression was used to analyze risk factors and to establish a nomogram. The accuracy of the model was assessed by C-index and calibration curve. TA-TMA class was associated with an over twofold increase in the risk of death (HR 2.66, 95% CI 1.39-5.09, p = 0.003). Stage III or IV acute graft-versus-host disease (aGVHD) (OR: 6.17, 95% CI: 2.19-17.18, p < 0.001) and occurrence time of aGVHD were the risk factors for TA-TMA. Next, we put these two variants and the other three variants into the prediction model via multivariate Lasso regression. In order to quantify the contribution of each factor, a nomogram was generated and displayed (C index of 0.783). TA-TMA predicts worsened outcomes of overall survival. A cross-validated multivariate score including aGVHD occurrence showed excellent concordance and efficacy of predicting TA-TMA in HSCT patients.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Microangiopatías Trombóticas , Enfermedad Injerto contra Huésped/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/terapia , Estudios Retrospectivos , Factores de Riesgo , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/etiologíaRESUMEN
Background: Machine learning methods showed excellent predictive ability in a wide range of fields. For the survival of head and neck squamous cell carcinoma (HNSC), its multi-omics influence is crucial. This study attempts to establish a variety of machine learning multi-omics models to predict the survival of HNSC and find the most suitable machine learning prediction method. Methods: The HNSC clinical data and multi-omics data were downloaded from the TCGA database. The important variables were screened by the LASSO algorithm. We used a total of 12 supervised machine learning models to predict the outcome of HNSC survival and compared the results. In vitro qPCR was performed to verify core genes predicted by the random forest algorithm. Results: For omics of HNSC, the results of the twelve models showed that the performance of multi-omics was better than each single-omic alone. Results were presented, which showed that the Bayesian network(BN) model (area under the curve [AUC] 0.8250, F1 score=0.7917) and random forest(RF) model (area under the curve [AUC] 0.8002,F1 score=0.7839) played good prediction performance in HNSC multi-omics data. The results of in vitro qPCR were consistent with the RF algorithm. Conclusion: Machine learning methods could better forecast the survival outcome of HNSC. Meanwhile, this study found that the BN model and the RF model were the most superior. Moreover, the forecast result of multi-omics was better than single-omic alone in HNSC.
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BACKGROUND: In the student-centered modern teaching environment of higher education, the affective domain was of great value to the overall development of medical students and the sustainable development of medical education. However, in the teaching practice of the medical specialty in Our country, there are still a lot of phenomena that pay attention to knowledge teaching but neglect affective education. Compared with affective domain, teachers tended to focus on the learning of specialized knowledge and skills. This paper investigated the attitudes and evaluations of teachers and students of medical school on affective education, analyzed the current situation and problems of teaching in the affective educauion of medical professions, and explored the path of combining the affective field and medical profession from the perspective of medical teachers. METHODS: A questionnaire survey was conducted among medical teachers and students across the country. Using the self-appointed teacher scale and the student scale to obtain their ratings of all dimensions of teaching in the affective field through a free online tool called "WenJuanXing". Descriptive statistics and multiple regression analysis methods were used to analyze the data to explore the obstacles in affective education and the factors affecting the outcome of affective education. RESULTS: A total of 523 medical teachers and 3268 medical students were surveyed, according to the results of questionnaire data analysis, there are differences in the needs of senior and lower grade students in various dimensions of affective education, and the current Chinese medical teachers carrying out affective education are facing unclear positioning and interpretation of affective education goals, lack of affective experience in teaching methods, lack of affective education evaluation norms, lack of continuity and progressivity of affective cultivation, and school organizational mechanisms need to be improved. CONCLUSIONS: This paper had some suggestions aimed at the above problem. Firstly, It is necessary to strengthen the construction of the organizational mechanism of medical universities, provide them with guarantees and training according to the characteristics of teachers of different teaching ages, and comprehensively improve teachers' affective literacy from the inside out. Secondly, teachers should design clear progressive goals and content systems of affective education, constructing an evaluation system of affective education in the experiential teaching method.