Synthetic Data as Validation

This study leverages synthetic data as a validation set to reduce overfitting and ease the selection of the best model in AI development. While synthetic data have been used for augmenting the training set, we find that synthetic data can also significantly diversify the validation set, offering marked advantages in domains like healthcare, where data are typically limited, sensitive, and from out-domain sources (i.e., hospitals). In this study, we illustrate the effectiveness of synthetic data for early cancer detection in computed tomography (CT) volumes, where synthetic tumors are generated and superimposed onto healthy organs, thereby creating an extensive dataset for rigorous validation. Using synthetic data as validation can improve AI robustness in both in-domain and out-domain test sets. Furthermore, we establish a new continual learning framework that continuously trains AI models on a stream of out-domain data with synthetic tumors. The AI model trained and validated in dynamically expanding synthetic data can consistently outperform models trained and validated exclusively on real-world data. Specifically, the DSC score for liver tumor segmentation improves from 26.7% (95% CI: 22.6%-30.9%) to 34.5% (30.8%-38.2%) when evaluated on an in-domain dataset and from 31.1% (26.0%-36.2%) to 35.4% (32.1%-38.7%) on an out-domain dataset. Importantly, the performance gain is particularly significant in identifying very tiny liver tumors (radius < 5mm) in CT volumes, with Sensitivity improving from 33.1% to 55.4% on an in-domain dataset and 33.9% to 52.3% on an out-domain dataset, justifying the efficacy in early detection of cancer. The application of synthetic data, from both training and validation perspectives, underlines a promising avenue to enhance AI robustness when dealing with data from varying domains

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro

BACKGROUND: Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. METHODS: Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants’ surfaces were observed with electron microscope. RESULTS: The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a “nest-shaped” way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day’s release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. CONCLUSIONS: Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was an ideal drug delivery system for the antibiotics. Biocompatibility tests demonstrated that the INH-PLLA implant did not have cytotoxicity. The multilayer donut-shaped tablet provided a new constant slow release method after an initial burst for the topical application of the antibiotic

Label-Free Liver Tumor Segmentation

We demonstrate that AI models can accurately segment liver tumors without the need for manual annotation by using synthetic tumors in CT scans. Our synthetic tumors have two intriguing advantages: (I) realistic in shape and texture, which even medical professionals can confuse with real tumors; (II) effective for training AI models, which can perform liver tumor segmentation similarly to the model trained on real tumors -- this result is exciting because no existing work, using synthetic tumors only, has thus far reached a similar or even close performance to real tumors. This result also implies that manual efforts for annotating tumors voxel by voxel (which took years to create) can be significantly reduced in the future. Moreover, our synthetic tumors can automatically generate many examples of small (or even tiny) synthetic tumors and have the potential to improve the success rate of detecting small liver tumors, which is critical for detecting the early stages of cancer. In addition to enriching the training data, our synthesizing strategy also enables us to rigorously assess the AI robustness.Comment: CVPR 202

Overexpression of the Wheat (Triticum aestivum L.) TaPEPKR2 Gene Enhances Heat and Dehydration Tolerance in Both Wheat and Arabidopsis

Wheat (Triticum aestivum L.) yield and quality are adversely affected by heat, drought, or the combination of these two stresses in many regions of the world. A phosphoenolpyruvate carboxylase kinase-related kinase gene, TaPEPKR2, was identified from our previous heat stress-responsive transcriptome analysis of heat susceptible and tolerant wheat cultivars. Based on the wheat cultivar Chinese Spring genome sequence, TaPEPKR2 was mapped to chromosome 5B. Expression analysis revealed that TaPEPKR2 was induced by heat and polyethylene glycol treatment. To analyze the function of TaPEPKR2 in wheat, we transformed it into the wheat cultivar Liaochun10, and observed that the transgenic lines exhibited enhanced heat and dehydration stress tolerance. To examine whether TaPEPKR2 exhibits the same function in dicotyledonous plants, we transformed it into Arabidopsis, and found that its overexpression functionally enhanced tolerance to heat and dehydration stresses. Our results imply that TaPEPKR2 plays an important role in both heat and dehydration stress tolerance, and could be utilized as a candidate gene in transgenic breeding

Genome-wide identification and expression profiling of auxin response factor (ARF) gene family in maize

<p>Abstract</p> <p>Background</p> <p>Auxin signaling is vital for plant growth and development, and plays important role in apical dominance, tropic response, lateral root formation, vascular differentiation, embryo patterning and shoot elongation. Auxin Response Factors (ARFs) are the transcription factors that regulate the expression of auxin responsive genes. The <it>ARF </it>genes are represented by a large multigene family in plants. The first draft of full maize genome assembly has recently been released, however, to our knowledge, the <it>ARF </it>gene family from maize (<it>ZmARF </it>genes) has not been characterized in detail.</p> <p>Results</p> <p>In this study, 31 maize (<it>Zea mays </it>L.) genes that encode ARF proteins were identified in maize genome. It was shown that maize <it>ARF </it>genes fall into related sister pairs and chromosomal mapping revealed that duplication of <it>ZmARFs </it>was associated with the chromosomal block duplications. As expected, duplication of some <it>ZmARFs </it>showed a conserved intron/exon structure, whereas some others were more divergent, suggesting the possibility of functional diversification for these genes. Out of these 31 <it>ZmARF </it>genes, 14 possess auxin-responsive element in their promoter region, among which 7 appear to show small or negligible response to exogenous auxin. The 18 <it>ZmARF </it>genes were predicted to be the potential targets of small RNAs. Transgenic analysis revealed that increased miR167 level could cause degradation of transcripts of six potential targets (<it>ZmARF3</it>, <it>9</it>, <it>16</it>, <it>18</it>, <it>22 </it>and <it>30</it>). The expressions of maize <it>ARF </it>genes are responsive to exogenous auxin treatment. Dynamic expression patterns of <it>ZmARF </it>genes were observed in different stages of embryo development.</p> <p>Conclusions</p> <p>Maize <it>ARF </it>gene family is expanded (31 genes) as compared to <it>Arabidopsis </it>(23 genes) and rice (25 genes). The expression of these genes in maize is regulated by auxin and small RNAs. Dynamic expression patterns of <it>ZmARF </it>genes in embryo at different stages were detected which suggest that maize <it>ARF </it>genes may be involved in seed development and germination.</p

Neuroprotective effect of TAT-14-3-3ε fusion protein against cerebral ischemia/reperfusion injury in rats.

Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB) due to its large size. A protein transduction domain (PTD) of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R) model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP), which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA) inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic activation