Artificial intelligence (AI) has contributed substantially to the resolution of a variety of biomedical problems, including cancer, over the past decade. Deep learning, a subfield of AI that is ...highly flexible and supports automatic feature extraction, is increasingly being applied in various areas of both basic and clinical cancer research. In this review, we describe numerous recent examples of the application of AI in oncology, including cases in which deep learning has efficiently solved problems that were previously thought to be unsolvable, and we address obstacles that must be overcome before such application can become more widespread. We also highlight resources and datasets that can help harness the power of AI for cancer research. The development of innovative approaches to and applications of AI will yield important insights in oncology in the coming decade.
Artificial intelligence (AI) has contributed substantially to the resolution of a variety of biomedical problems, including cancer, over the past decade. In this review, we describe numerous recent examples of the application of AI in oncology, including cases in which deep learning has efficiently solved problems that were previously thought to be unsolvable, and we address obstacles that must be overcome before such application can become more widespread.
Glucose metabolism is remodeled in cancer, but the global pattern of cancer-specific metabolic changes remains unclear. Here we show, using the comprehensive measurement of metabolic enzymes by ...large-scale targeted proteomics, that the metabolism both carbon and nitrogen is altered during the malignant progression of cancer. The fate of glutamine nitrogen is shifted from the anaplerotic pathway into the TCA cycle to nucleotide biosynthesis, with this shift being controlled by glutaminase (GLS1) and phosphoribosyl pyrophosphate amidotransferase (PPAT). Interventions to reduce the PPAT/GLS1 ratio suppresses tumor growth of many types of cancer. A meta-analysis reveals that PPAT shows the strongest correlation with malignancy among all metabolic enzymes, in particular in neuroendocrine cancer including small cell lung cancer (SCLC). PPAT depletion suppresses the growth of SCLC lines. A shift in glutamine fate may thus be required for malignant progression of cancer, with modulation of nitrogen metabolism being a potential approach to SCLC treatment.
We will introduce and outline some points regarding the diagnosis and treatment of non-dissecting thoracic aortic aneurysms from JCS/JSCS/JATS/JSVS 2020 Guideline on Diagnosis and Treatment of Aortic ...Aneurysm and Aortic Dissection.
Plants would be more vulnerable to water stress and thereafter rewatering or a cycled water environmental change, which occur more frequently under climatic change conditions in terms of the ...prediction scenarios. Effects of water stress on plants alone have been well-documented in many reports. However, the combined responses to drought and rewatering and its mechanism are relatively scant. As we known, plant growth, photosynthesis and stomatal aperture may be limited under water deficit, which would be regulated by physical and chemical signals. Under severe drought, while peroxidation may be provoked, the relevant antioxidant metabolism would be involved to annihilate the damage of reactive oxygen species. As rewatering, the recoveries of plant growth and photosynthesis would appear immediately through growing new plant parts, re-opening the stomata, and decreasing peroxidation; the recovery extents (reversely: pre-drought limitation) due to rewatering strongly depend on pre-drought intensity, duration and species. Understanding how plants response to episodic drought and watering pulse and the underlying mechanism is remarkably helpful to implement vegetation management practices in climatic changing.
We reviewed the results of endovascular aneurysm repair in patients from the Japanese Committee for Stentgraft Management registry to determine the significance of persistent type II endoleak ...(p-T2EL) and the risk of late adverse events, including aneurysm sac enlargement.
The prospectively captured medical records of 17 099 patients <75 years of age who underwent endovascular aneurysm repair for abdominal aortic aneurysm from 2006 to 2015 were reviewed. Patients were divided into 2 groups (with or without p-T2EL) and compared to examine the correlation between p-T2EL and the occurrence of aneurysm sac enlargement after endovascular aneurysm repair.
Of the patients, 4957 (29.0%) had p-T2EL and 12 142 (71.0%) had no p-T2EL (non-T2EL). Mean age was significantly higher (
<0.001), and there were fewer men (
<0.001) in the p-T2EL group. Among comorbidities, hypertension (
=0.019) and chronic kidney disease (
=0.040) were more prevalent and respiratory disorders were less prevalent (
<0.001) in the p-T2EL group. From each group, 4957 patients were matched according to propensity score to adjust for differences in patient characteristics. The cumulative incidence rates of abdominal aortic aneurysm-related mortality (p-T2EL: 52 of 4957 1.0% versus non-T2EL: 21 of 12 142 0.2%), rupture (p-T2EL: 38 of 4957 0.8% versus non-T2EL: 13 of 12 142 0.1%), sac enlargement (≥5 mm; p-T2EL: 1359 of 4957 27.4% versus non-T2EL: 332 of 12 142 2.7%), and reintervention (p-T2EL: 739 of 4957 14.9% versus non-T2EL: 91 of 12 142 0.7%) were significantly higher in the p-T2EL than the nonpT2EL group (
<0.001). Propensity score matching yielded higher estimated incremental risk, including abdominal aortic aneurysm-related mortality, rupture, sac enlargement (≥5 mm), and reintervention for p-T2EL (
<0.001). Cox regression analysis revealed older age (
=0.010), proximal neck diameter (
=0.003), and chronic kidney disease (
<0.001) as independent positive predictors and male sex as an independent negative predictor (
=0.015) of sac enlargement.
The Japanese Committee for Stentgraft Management registry data show a correlation between p-T2EL and late adverse events, including aneurysm sac enlargement, reintervention, rupture, and abdominal aortic aneurysm-related mortality after endovascular aneurysm repair. Besides p-T2EL, older age, female sex, chronic kidney disease, and dilated proximal neck were associated with sac enlargement.
Although the relationship between grassland productivity and soil water status has been extensively researched, the responses of plant growth and photosynthetic physiological processes to long-term ...drought and rewatering are not fully understood. Here, the perennial grass (Leymus chinensis), predominantly distributed in the Euro-Asia steppe, was used as an experimental plant for an irrigation manipulation experiment involving five soil moisture levels 75-80, 60-75, 50-60, 35-50, and 25-35% of soil relative water content (SRWC), i.e. the ratio between present soil moisture and field capacity to examine the effects of soil drought and rewatering on plant biomass, relative growth rate (RGR), and photosynthetic potential. The recovery of plant biomass following rewatering was lower for the plants that had experienced previous drought compared with the controls; the extent of recovery was proportional to the intensity of soil drought. However, the plant RGR, leaf photosynthesis, and light use potential were markedly stimulated by the previous drought, depending on drought intensity, whereas stomatal conductance (gs) achieved only partial recovery. The results indicated that gs may be responsible for regulating actual photosynthetic efficiency. It is assumed that the new plant growth and photosynthetic potential enhanced by pre-drought following rewatering may try to overcompensate the great loss of the plant's net primary production due to the pre-drought effect. The present results highlight the episodic effects of drought on grass growth and photosynthesis. This study will assist in understanding how degraded ecosystems can potentially cope with climate change.
Abstract Objectives This study sought to clarify the incidence and predictors of hypoattenuated leaflet thickening (HALT) and mid-term outcomes after transcatheter aortic valve replacement. ...Background HALT detected on multidetector computed tomography (MDCT) scanning raised concerns about possible subclinical leaflet thrombosis. Methods We studied 70 of 100 consecutive patients from a single-center registry who underwent implantation with the Edwards SAPIEN-XT device. MDCT results, echocardiographic data, and laboratory findings obtained at the 6-month and 1-year follow-ups were analyzed. Results Of 70 patients, MDCT scans revealed HALT in 1 patient (1.4%) at discharge, 7 (10.0%) at 6 months, and 10 (14.3%) at 1 year post–transcatheter aortic valve replacement cumulatively. The degree of leaflet immobility correlated with the HALT area on 4-dimensional MDCT (r = 0.68) on the basis of data from 10 patients. HALT was associated with male sex (70% vs. 25%; p = 0.008) and larger sinus of Valsalva (31.0 ± 2.0 mm vs. 28.6 ± 2.6 mm; p = 0.005). HALT was found in 3 of 49 patients with a 23-mm bioprosthesis and in 7 of 21 patients with a 26-mm bioprosthesis (6.1% vs. 33.3%; p = 0.006). D-dimer levels were significantly increased in the HALT group at the 6-month (2.3 μg/ml interquartile range (IQR): 2.1 to 6.1 μg/ml vs. 1.1 μg/ml IQR: 0.8 to 2.2 μg/ml; p = 0.002) and 1-year (2.7 μg/ml IQR: 1.7 to 4.8 μg/ml vs. 1.2 μg/ml IQR: 0.9 to 2.1 μg/ml; p = 0.006) follow-ups, despite no differences at discharge. The pressure gradient was decreased in the HALT group at the 1-year follow-up (8.3 ± 0.8 mm Hg vs. 11.1 ± 4.9 mm Hg; p = 0.005). After detecting HALT, additional anticoagulation therapy was not administered. Clinical outcomes, including all-cause mortality (0% vs. 1.7%; p = 1.00) and stroke (0% vs. 0%; p = 1.00), were similar between the groups. Conclusions HALT with reduced leaflet motion was not rare but usually subclinical. Valve hemodynamics and mid-term outcomes were uneventful even without additional anticoagulant therapy in our limited number of cases. Male sex, larger sinus and bioprosthesis size, and elevated D-dimer levels during follow-up were associated with this phenomenon.
The chloroplast NAD(P)H dehydrogenase (NDH) complex is involved in photosystem I (PSI) cyclic and chlororespiratory electron transport in higher plants. Although biochemical and genetic evidence for ...its subunit composition has accumulated, it is not enough to explain the complexes putative activity of NAD(P)H-dependent plastoquinone reduction. We analyzed the NDH complex by using blue native PAGE and found that it interacts with PSI to form a novel supercomplex. Mutants lacking NdhL and NdhM accumulated a pigment-protein complex with a slightly lower molecular mass than that of the NDH-PSI supercomplex; this may be an intermediate supercomplex including PSI. This intermediate is unstable in mutants lacking NdhB, NdhD, or NdhF, implying that it includes some NDH subunits. Analysis of thylakoid membrane complexes using sucrose density gradient centrifugation supported the presence of the NDH-PSI supercomplex in vivo. Although the NDH complex exists as a monomer in etioplasts, it interacts with PSI to form a supercomplex within 48 h during chloroplast development.
Acute aortic dissection (AAD) is a life-threatening vascular disease without effective pharmaceutical therapy. Matrix metalloproteinases (MMPs) are implicated in the development of chronic vascular ...diseases including aneurysm, but the key effectors and mechanism of action remain unknown. To define further the role of MMPs in AAD, we screened circulating MMPs in AAD patients, and then generated a novel mouse model for AAD to characterize the mechanism of action.
MMP9 and angiotensin II were elevated significantly in blood samples from AAD patients than in those from the patients with nonruptured chronic aortic aneurysm or healthy volunteers. Based on the findings, we established a novel AAD model by infusing angiotensin II to immature mice that had been received a lysyl oxidase inhibitor, β-aminopropionitrile monofumarate. AAD was developed successfully in the thoracic aorta by angiotensin II administration to β-aminopropionitrile monofumarate-treated wild-type mice, with an incidence of 20%, 80%, and 100% after 6, 12, and 24 hours, respectively. Neutrophil infiltrations were observed in the intima of the thoracic aorta, and the overexpression of MMP9 in the aorta was demonstrated by reverse transcription polymerase chain reaction, gelatin zymography, and immunohistochemistry. The incidence of AAD was reduced significantly by 40% following the administration of an MMP inhibitor and was almost blocked completely in MMP(-/-) mice without any influence on neutrophil infiltration. Neutrophil depletion by injection of anti-granulocyte-differentiation antigen-1 (anti-Gr-1) antibody also significantly decreased the incidence of AAD.
These data suggest that AAD is initiated by neutrophils that have infiltrated the aortic intima and released MMP9 in response to angiotensin II.
Warming, watering and elevated atmospheric CO₂-concentration effects have been extensively studied separately; however, their combined impact on plants is not well understood. In the current ...research, we examined plant growth and physiological responses of three dominant species from the Eurasian Steppe with different functional traits to a combination of elevated CO₂, high temperature, and four simulated precipitation patterns. Elevated CO₂ stimulated plant growth by 10.8–41.7 % for a C₃ leguminous shrub, Caragana microphylla, and by 33.2–52.3 % for a C₃ grass, Stipa grandis, across all temperature and watering treatments. Elevated CO₂, however, did not affect plant biomass of a C₄ grass, Cleistogenes squarrosa, under normal or increased precipitation, whereas a 20.0–69.7 % stimulation of growth occurred with elevated CO₂ under drought conditions. Plant growth was enhanced in the C₃ shrub and the C₄ grass by warming under normal precipitation, but declined drastically with severe drought. The effects of elevated CO₂ on leaf traits, biomass allocation and photosynthetic potential were remarkably species-dependent. Suppression of photosynthetic activity, and enhancement of cell peroxidation by a combination of warming and severe drought, were partly alleviated by elevated CO₂. The relationships between plant functional traits and physiological activities and their responses to climate change were discussed. The present results suggested that the response to CO₂ enrichment may strongly depend on the response of specific species under varying patterns of precipitation, with or without warming, highlighting that individual species and multifactor dependencies must be considered in a projection of terrestrial ecosystem response to climatic change.
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