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Conventional deep learning (DL) algorithm requires full supervision of annotating the region of interest (ROI) that is laborious and often biased. We aimed to develop a weakly-supervised DL algorithm that diagnosis breast cancer at ultrasound without image annotation. Weakly-supervised DL algorithms were implemented with three networks (VGG16, ResNet34, and GoogLeNet) and trained using 1000 unannotated US images (500 benign and 500 malignant masses). Two sets of 200 images (100 benign and 100 malignant masses) were used for internal and external validation sets. For comparison with fully-supervised algorithms, ROI annotation was performed manually and automatically. Diagnostic performances were calculated as the area under the receiver operating characteristic curve (AUC). Using the class activation map, we determined how accurately the weakly-supervised DL algorithms localized the breast masses. For internal validation sets, the weakly-supervised DL algorithms achieved excellent diagnostic performances, with AUC values of 0.92–0.96, which were not statistically different (all Ps > 0.05) from those of fully-supervised DL algorithms with either manual or automated ROI annotation (AUC, 0.92–0.96). For external validation sets, the weakly-supervised DL algorithms achieved AUC values of 0.86–0.90, which were not statistically different (Ps > 0.05) or higher (P = 0.04, VGG16 with automated ROI annotation) from those of fully-supervised DL algorithms (AUC, 0.84–0.92). In internal and external validation sets, weakly-supervised algorithms could localize 100% of malignant masses, except for ResNet34 (98%). The weakly-supervised DL algorithms developed in the present study were feasible for US diagnosis of breast cancer with well-performing localization and differential diagnosis. [ABSTRACT FROM AUTHOR]

Conventionally, apnea–hypopnea index (AHI) is used to define and categorize the severity of obstructive sleep apnea. However, routine polysomnography (PSG) includes multiple parameters for assessing the severity of obstructive sleep apnea. The goal of this study is to identify and categorize obstructive sleep apnea phenotypes using unsupervised learning methods from routine PSG data. We identified four clusters from 4,603 patients by using 29 PSG variable and arranged according to their mean AHI. Cluster 1, spontaneous arousal (mean AHI = 8.52/h); cluster 2, poor sleep and periodic limb movements (mean AHI = 12.16/h); cluster 3, hypopnea (mean AHI = 38.60/h); and cluster 4, hypoxia (mean AHI = 69.66/h). Conventional obstructive sleep apnea classification based on apnea–hypopnea index severity showed no significant difference in cardiovascular or cerebrovascular mortality (Log rank P = 0.331), while 4 clusters showed an overall significant difference (Log rank P = 0.009). The risk of cardiovascular or cerebrovascular mortality was significantly increased in cluster 2 (hazard ratio = 6.460, 95% confidence interval 1.734–24.073) and cluster 4 (hazard ratio = 4.844, 95% confidence interval 1.300–18.047) compared to cluster 1, which demonstrated the lowest mortality. After adjustment for age, sex, body mass index, and underlying medical condition, only cluster 4 showed significantly increased risk of mortality compared to cluster 1 (hazard ratio = 7.580, 95% confidence interval 2.104–34.620). Phenotyping based on numerous PSG parameters gives additional information on patients' risk evaluation. Physicians should be aware of PSG features for further understanding the pathophysiology and personalized treatment. [ABSTRACT FROM AUTHOR]

Activated macrophages show increased expression of vimentin, an intermediate filament protein. Macrophages secrete vimentin into extracellular space; however, the functions of extracellular vimentin and the process of vimentin secretion are not clearly defined. We found that oxidized low-density lipoproteins (oxLDL) via CD36 induced vimentin secretion in macrophages. We also revealed that extracellular vimentin induced macrophages to release inflammatory cytokines and augmented oxLDL-induced release of TNF-α and IL-6. Extracellular vimentin activated NF-κB signaling via phosphorylation of focal adhesion kinase (p-FAK) and IκB kinase (p-IκK). Extracellular vimentin also amplified the oxLDL-induced p-IκK increase and IκB decrease. Vimentin-induced TNF-α release was not dependent on Dectin-1, which is known to bind vimentin. We measured serum vimentin concentrations and found that patients with atherosclerotic coronary artery disease had higher levels of serum vimentin than normal subjects. Circulating oxLDL and vimentin concentrations showed a high degree of correlation. In mouse experiments, vimentin concentration was higher in the sera of apoE null mice with western diet–induced atherosclerosis than in the sera of chow diet–fed apoE null mice without atherosclerosis. We concluded that vimentin is secreted by oxLDL/CD36 interaction in macrophages and extracellular vimentin promotes macrophage release of pro-inflammatory cytokines. This may contribute to atherosclerotic inflammation and based on our analysis of serum vimentin, we suggest serum vimentin as a predictive marker for atherosclerosis. Key messages: OxLDL via CD36 induces secretion of vimentin, a cytoskeletal protein in macrophages. Extracellular vimentin induces macrophages to release proinflammatory cytokines such as tumor necrotizing factor-alpha (TNF-α) and this process is mediated by activation of focal adhesion kinase (FAK) and NF-ƙB signaling. Serum concentrations of vimentin in coronary artery disease patients are higher than that in control group. Vimentin concentration is strongly correlated with oxLDL concentration in serum. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of training radiology residents on breast ultrasonography (US) according to the Breast Imaging Reporting And Data System (BI-RADS) and the factors that influence the training effect.Methods: This multicenter, prospective study was approved by eight institutional review boards. From September 2013 to July 2014, 248 breast masses in 227 women were included for US image acquisition. Representative B-mode and video images of the breast masses were recorded, among which 54 cases were included in the education set and 66 in the test set. Sixty-one radiology residents scheduled for breast imaging training individually reviewed the test set, immediately before, 1 month after, and 6 months after training. Diagnostic performances and US descriptors of the residents were evaluated and compared against those of expert radiologists.Results: Agreements between residents and experienced radiologists showed improvement after training, while agreements between post-training and post-6-month training descriptors did not show significant differences (all p > 0.05, respectively). Sensitivity, negative predictive value (NPV), and AUC were significantly improved for residents post-training and post-6-month training (all p < 0.05), while approximating the performances of expert radiologists except for AUC (0.836, 0.840, and 0.908, respectively, p < 0.05). Low levels of pre-training AUC, total number of breast US examinations, and the number of sessions per week that residents were involved in were factors influencing the improvement of AUC.Conclusion: Training using education material dedicated for breast US imaging effectively improved the diagnostic performances of radiology residents and agreements with experienced radiologists on US BI-RADS features.Key Points: • Agreements on lesion descriptors between residents and experienced radiologists showed improvement after training, regardless of test point. • Sensitivity, NPV, and AUC were significantly improved for residents in post-training and post-6-month training (all p < 0.05). • Low levels of pre-training AUC, total number of breast US examinations, and the number of sessions per week that residents were involved in were factors influencing the improvement of AUC. [ABSTRACT FROM AUTHOR]

Obesity is generally caused by quantitative changes in adipocyte differentiation and fat metabolism. Only a few studies have been determined the effect of red beans extract on obesity and plasma cholesterol concentration. We have been studied the functional activities of red-bean extracts including anti-oxidative effect against DNA and cell damages. Histological study including micro CT analysis showed that the accumulation of fat in hepatocytes and intestines was significantly decreased in red bean extract treated group. In addition, plasma cholesterol and triglyceride levels were decreased in blood samples. In addition, it was confirmed that the red bean extract inhibited the expression of PPARγ, Fabp4 and RETN genes, which regulate total adipocyte differentiation and lipid metabolism. Red bean extract inhibits the expressions of transcription factors associated with adipocyte differentiation in a dose-dependent manner, thereby inhibiting fat accumulation and decreasing blood lipid levels in obese mice induced by high fat diet. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer with lymphoid stroma (GCLS) is pathologically characterized by poorly developed tubular structures with a prominent lymphocytic infiltration. Its clinical and prognostic features differ in patients positive and negative for Epstein-Barr virus (EBV) infection. This study analyzed the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and the density of tumor-infiltrating lymphocytes (TILs) including CD3+ and CD8+ T cells, as well as their prognostic significance in patients with GCLS.Methods: The study included 58 patients with GCLS (29 EBV+ and 29 EBV−) who underwent curative resection. Expression of CD3, CD8, PD-1, and PD-L1 in tumor cells and TILs was analyzed using a quantitative multispectral imaging system (Opal™), with these results validated by immuno-histochemical assays for PD-L1 on whole slide sections.Results: The proportion of tumors overexpressing PD-L1 (31.0 vs. 0%, P = 0.002), TIL density (4548 vs. 2631/mm2, P < 0.001), and intra-tumoral CD8+ T-cell density (2650 vs. 1060/mm2, P < 0.001) were significantly higher in EBV+ than in EBV− GCLS. In addition, CD8+/CD3+ T-cell ratio was higher in EBV+ than in EBV− GCLS (55.3 vs. 35.8%, P < 0.001). Lower TIL density, defined as < 1350/mm2, was a significant negative factor of survival.Conclusions: Despite histopathological similarity, quantitative multispectral imaging revealed differences in the tumor immune micro-environment between EBV+ and EBV− GCLS, indicating that the underlying pathogenesis differs in these two disease entities. TIL density may be a prognostic marker in patients with GCLS. [ABSTRACT FROM AUTHOR]

Fibromatosis refers to an extra-abdominal desmoid tumor or aggressive fibromatosis. Breast fibromatosis can develop in association with the capsule around a breast implant, although reports of cases of fibromatosis associated with breast implants are rare. As the demand for breast augmentation has increased, it is important to understand the diseases associated with breast implants. In the present report, we describe a case of breast fibromatosis that developed adjacent to a breast implant and demonstrated a relatively well-defined border even though it invaded the surrounding structures. We also explore the specific imaging features for diagnosing breast fibromatosis in association with implants by reviewing previous literature. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is often complicated by coronary artery lesions (CALs), including aneurysms. Because of the complications associated with KD, this disorder is the leading cause of acquired heart disease in children from developed countries. To identify genetic loci that confer a higher risk of developing CALs, we performed a case-control association study using previous genome-wide association study data for samples from KD cases only (n=186) by grouping KD patients without CALs (control: n=123) vs KD patients with extremely large aneurysms (diameter>5 mm) (case: n=17). Twelve loci with one or more sequence variants were found to be significantly associated with CALs (P<1 × 10−5). Of these, an SNP (rs17136627) in the potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 (KCNN2) at 5q22.3 was validated in 32 KD patients with large aneurysms (diameter>5 mm) and 191 KD patients without CALs (odds ratio (OR)=12.6, Pcombined=1.96 × 10−8). This result indicates that the KCNN2 gene can have an important role in the development of coronary artery aneurysms in KD. [ABSTRACT FROM AUTHOR]

Height is a highly heritable trait that involves multiple genetic loci. To identify causal variants that influence stature, we sequenced whole exomes of four children with idiopathic short stature. Ninety-five nonsynonymous single-nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants. We performed association analysis in 740 cohort individuals and identified 11 nsSNPs in 10 loci ( DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN, FAM59A, and NINL) associated with adult height ( P < 0.05), including five novel loci. Of these, two nsSNPs ( TSSC4 and KIF18A loci) were significant at P < 0.05 in the replication study ( n = 1,000) and five ( ZBTB38, FAM154A, TSSC4, KIF18A, and FAM59A loci) were significant at P < 0.01 in the combined analysis ( n = 1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height variation. This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate and compare the diagnostic performances of the deep convolutional neural network (CNN) and expert radiologists for differentiating thyroid nodules on ultrasonography (US), and to validate the results in multicenter data sets. This multicenter retrospective study collected 15,375 US images of thyroid nodules for algorithm development (n = 13,560, Severance Hospital, SH training set), the internal test (n = 634, SH test set), and the external test (n = 781, Samsung Medical Center, SMC set; n = 200, CHA Bundang Medical Center, CBMC set; n = 200, Kyung Hee University Hospital, KUH set). Two individual CNNs and two classification ensembles (CNNE1 and CNNE2) were tested to differentiate malignant and benign thyroid nodules. CNNs demonstrated high area under the curves (AUCs) to diagnose malignant thyroid nodules (0.898–0.937 for the internal test set and 0.821–0.885 for the external test sets). AUC was significantly higher for CNNE2 than radiologists in the SH test set (0.932 vs. 0.840, P < 0.001). AUC was not significantly different between CNNE2 and radiologists in the external test sets (P = 0.113, 0.126, and 0.690). CNN showed diagnostic performances comparable to expert radiologists for differentiating thyroid nodules on US in both the internal and external test sets. [ABSTRACT FROM AUTHOR]

The original version of this article, published on 07 January 2019, unfortunately contained a mistake. [ABSTRACT FROM AUTHOR]

Microgravity in space impacts human health. In particular, thyroid cancer, which has a high incidence rate, has been the subject of numerous studies with respect to microgravity. However, most studies have focused on Western follicular thyroid cancer cell lines, while data regarding the effects of microgravity on Asian cell lines are lacking. Therefore, we aimed to investigate the effect of simulated ground-based microgravity on two Korean thyroid cancer cell lines, namely SNU-790 and SNU-80. We found that both cell lines formed multicellular spheroids under simulated microgravity. Gene expression analysis revealed that in SNU-790 cells, histone-related genes were upregulated and microRNA-related genes were downregulated. Meanwhile, in SNU-80 cells, genes related to the cellular response to hypoxia were downregulated. These findings contribute to a better understanding of the effects of microgravity on thyroid cancer cells. Further validation studies and clinical significance analyses are needed to fully understand the implications of these findings. [ABSTRACT FROM AUTHOR]

We study whether deep neural network based algorithm can filter out mammography phantom images that will pass or fail. With 543 phantom images generated from a mammography unit, we created VGG16 based phantom shape scoring models (multi-and binary-class classifiers). Using these models we designed filtering algorithms that can filter failed or passed phantom images. 61 phantom images obtained from two different medical institutions were used for external validation. The performances of the scoring models show an F1-score of 0.69 (95% confidence interval (CI) 0.65, 0.72) for multi-class classifiers and an F1-score of 0.93 (95% CI 0.92, 0.95) and area under the receiver operating characteristic curve of 0.97 (95% CI 0.96, 0.98) for binary-class classifiers. A total of 42 of the 61 phantom images (69%) were filtered by the filtering algorithms without further need for assessment from a human observer. This study demonstrated the potential to reduce the human workload from mammographic phantom interpretation using the deep neural network based algorithm. [ABSTRACT FROM AUTHOR]

Enterococcus faecalis, a gram-positive bacterium, is among the most common nosocomial pathogens due to its limited susceptibility to antibiotics and its reservoir of the genes coding for virulence factors. Bacterial enzymes such as kinases and phosphorylases play important roles in diverse functions of a bacterial cell and, thus, are potential antibacterial drug targets. In Gram-positive bacteria, HPr Kinase/Phosphorylase (HPrK/P), a bifunctional enzyme is involved in the regulation of carbon catabolite repression by phosphorylating/dephosphorylating the histidine-containing phosphocarrier protein (HPr) at Ser46 residue. Deficiencies in HPrK/P function leads to severe defects in bacterial growth. This study aimed at identifying novel inhibitors of E. faecalis HPrK/P from a commercial compound library using structure-based virtual screening. The hit molecules were purchased and their effect on enzyme activity and growth of resistant E. faecalis was evaluated in vitro. Furthermore, docking and molecular dynamics simulations were performed to study the interactions of the hit compounds with HPrK/P. Among the identified hit molecules, two compounds inhibited the phosphorylation of HPr as well as significantly reduced the growth of resistant E. faecalis in vitro. These identified potential HPrK/P inhibitors open new research avenues towards the development of novel antimicrobials against resistant Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

Background: Mini-screws are widely used as temporary anchorages in orthodontic treatment, but have the disadvantage of showing a high failure rate of about 10%. Therefore, orthodontic mini-screws should have high biocompatibility and retention. Previous studies have demonstrated that the retention of mini-screws can be improved by imparting bioactivity to the surface. The method for imparting bioactivity proposed in this paper is to sequentially perform anodization, periodic pre-calcification, and heat treatments with a Ti–6Al–4V ELI alloy mini-screw. Materials and methods: A TiO2 nanotube-structured layer was formed on the surface of the Ti–6Al–4V ELI alloy mini-screw through anodization in which a voltage of 20 V was applied to a glycerol solution containing 20 wt% H2O and 1.4 wt% NH4F for 60 min. Fine granular calcium phosphate precipitates of HA and octacalcium phosphate were generated as clusters on the surface through the cyclic pre-calcification and heat treatments. The cyclic pre-calcification treatment is a process of immersion in a 0.05 M NaH2PO4 solution and a saturated Ca(OH)2 solution at 90 °C for 1 min each. Results: It was confirmed that the densely structured protrusions were precipitated, and Ca and P concentrations, which bind and concentrate endogenous bone morphogenetic proteins, increased on the surface after simulated body fluid (SBF) immersion test. In addition, the removal torque of the mini-screw fixed into rabbit tibias for 4 weeks was measured to be 8.70 ± 2.60 N cm. Conclusions: A noteworthy point in this paper is that the Ca and P concentrations, which provide a scaffold suitable for endogenous bone formation, further increased over time after SBF immersion of the APH group specimens. The other point is that our mini-screws have a significantly higher removal torque compared to untreated mini-screws. These results represent that the mini-screw proposed in this paper can be used as a mini-screw for orthodontics. [ABSTRACT FROM AUTHOR]

Background and Aims: The influence of direct-acting antivirals (DAAs) on chronic hepatitis C (CHC)-related hepatocellular carcinoma (HCC) remains controversial. We investigated the effect of eradicating CHC using DAAs on treatment outcomes in patients with CHC-related HCC treated with transarterial chemoembolization (TACE). Methods: This nationwide, multi-center, retrospective study recruited patients with CHC-related HCC treated with TACE as the first-line anti-cancer treatment, and who achieved a sustained virological response (SVR) using DAAs (DAA group) between 2006 and 2017. Patients achieving an SVR following interferon-based treatment (IFN group) and those without treatment (control group) were also recruited for comparison. Results: A total of 425 patients were eligible for the study. Of these, 356 (83.8%), 26 (6.1%), and 43 (10.1%) were allocated to the control, IFN, and DAA groups, respectively. A multivariate analysis showed that liver cirrhosis, segmental portal vein thrombosis, and larger maximal tumor size independently predicted an increased risk of progression (all p < 0.05), whereas, the DAA group (vs. IFN and control groups) independently predicted a reduced risk of progression (hazard ratio (HR) = 0.630, 95% confidence interval 0.411–0.966, p = 0.034). The cumulative incidence rate of HCC progression in the DAA group was significantly lower than that in the IFN and control groups (p = 0.033, log-rank test). In addition, the DAA group (vs. IFN and control groups) was independently associated with a reduced risk of mortality (p = 0.042). Conclusions: DAA treatment provided significantly prolonged progression-free survival in patients with CHC-related HCC treated with TACE compared to that in patients administered IFN or no treatment. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) of the flaviviridae family, is the cause of emerging infections characterized by fever, Guillain-Barré syndrome (GBS) in adults and microcephaly in newborns. There exists an urgent unmet clinical need for anti-ZIKV drugs for the treatment of infected individuals. In the current work, we aimed at the promising virus drug target, ZIKV NS3 protease and constructed a Pharmacophore Anchor (PA) model for the active site. The PA model reveals a total of 12 anchors (E, H, V) mapped across the active site subpockets. We further identified five of these anchors to be critical core anchors (CEH1, CH3, CH7, CV1, CV3) conserved across flaviviral proteases. The ZIKV protease PA model was then applied in anchor-enhanced virtual screening yielding 14 potential antiviral candidates, which were tested by in vitro assays. We discovered FDA drugs Asunaprevir and Simeprevir to have potent anti-ZIKV activities with EC50 values 4.7 µM and 0.4 µM, inhibiting the viral protease with IC50 values 6.0 µM and 2.6 µM respectively. Additionally, the PA model anchors aided in the exploration of inhibitor binding mechanisms. In conclusion, our PA model serves as a promising guide map for ZIKV protease targeted drug discovery and the identified 'previr' FDA drugs are promising for anti-ZIKV treatments. [ABSTRACT FROM AUTHOR]

Common wild rice (Oryza rufipogon Griff.) is invaluable genetic resource for rice resistance breeding. Whole-genome re-sequencing was conducted to systematically analyze the variations in two new inbred lines (Huaye 3 and Huaye 4) developed from a common wild rice. A total of 4,841,127 SNPs, 1,170,479 InDels, 24,080 structural variations (SVs), and 298 copy number variations (CNVs) were identified in three materials. Approximately 16.24 and 5.64% of the total SNPs and InDels of Huaye 3 and Huaye 4 were located in genic regions, respectively. Together, 12,486 and 15,925 large-effect SNPs, and 12,417 and 14,513 large-effect InDels, which affect the integrity of the encoded protein, were identified in Huaye 3 and Huaye 4, respectively. The distribution map of 194 and 245 NBS-LRR encoding homologs was constructed across 12 rice chromosomes. Further, GO enrichment analysis of the homologs with identical genotype variations in Huaye 3 and Huaye 4 revealed 67, 82, and 58 homologs involved in cell death, response to stress, and both terms, respectively. Comparative analysis displayed that 550 out of 652 SNPs and 129 out of 147 InDels were present in a widely used blast-susceptible rice variety (LTH). Protein-protein interaction analysis revealed a strong interaction between NBS-LRR candidates and several known R genes. One homolog of disease resistance protein (RPM1) was involved in the plant-pathogen interaction pathway. Artificial inoculation of disease/insect displayed resistance phenotypes against rice blast and brown planthopper in two lines. The results will provide allele-specific markers for rice molecular breeding. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expansion of hematopoietic stem/progenitor cells (HSPCs) from umbilical cord blood using extracellular matrix (ECM) protein-coated three-dimensional hierarchical scaffolds. Results: The expansion of HSPCs was evaluated through total nucleated cell (TNC) expansion, immuno-phenotypic analysis, and clonogenic ability. After 7 days of culture, three-dimensional cultures with fibronectin-coated scaffolds achieved the highest fold increase in TNCs (164 ± 6.9 fold) and the highest CD45CD34 (35 %) and CD34CD38 (32 %) ratios. Conclusion: Three-dimensional hierarchical scaffolds were coated with ECM protein to simulate a biomimetic environment or niche, and had a significant effect on the expansion potential of HSPCs without changing their phenotype. [ABSTRACT FROM AUTHOR]

Abstract Background  Kawasaki disease (KD) is an acute vasculitis syndrome of unknown etiology that frequently affects small to medium size arteries. C-C chemokine receptor 5 (CCR5) is a chemokine receptor that binds C-C chemokines. This study investigated the association of the CCR5 (−2135C/T) polymorphism with KD in Korean children. Methods  The study population consisted 189 Korean children with KD and 194 Korean children with congenital heart disease (CHD). CCR5 (−2135C/T) polymorphism genotypes were determined using the single-base extension method. Results  The allele frequencies of the CCR5 (−2135C/T) polymorphism differed significantly between CHD children and KD children (−2135T/T, 16.75% vs. 30.05%, aOR 2.14, 95% CI 1.31–3.51). The tested laboratory parameters differed significantly between the KD and CHD groups. The development of coronary artery aneurysm in KD patients was not associated with the CCR5 polymorphism. Conclusions  Our findings suggest that the T allele at the CCR5 (−2135C/T) polymorphism might be associated with the development of KD in Korean children but does not appear to be associated with the development of coronary artery aneurysm. [ABSTRACT FROM AUTHOR]

Cultivated tomato, Solanum lycopersicum, is one of the most common fruits in the global food industry. Together with the wild tomato Solanum pennellii, it is widely used for developing better cultivars. MicroRNAs affect mRNA regulation, inhibiting its translation and/or promoting its degradation. Important proteins involved in these processes are ARGONAUTE and DICER. This study aimed to identify and characterize the genes involved in the miRNA processing pathway, miRNA molecules and target genes in both species. We validated the presence of pathway genes and miRNA in different NGS libraries and 6 miRNA families using quantitative RT-PCR. We identified 71 putative proteins in S. lycopersicum and 108 in S. pennellii likely involved in small RNAs processing. Of these, 29 and 32 participate in miRNA processing pathways, respectively. We identified 343 mature miRNAs, 226 pre-miRNAs in 87 families, including 192 miRNAs, which were not previously identified, belonging to 38 new families in S. lycopersicum. In S. pennellii, we found 388 mature miRNAs and 234 pre-miRNAs contained in 85 families. All miRNAs found in S. pennellii were unpublished, being identified for the first time in our study. Furthermore, we identified 2471 and 3462 different miRNA target in S. lycopersicum and S. pennellii, respectively. [ABSTRACT FROM AUTHOR]