Tumor volume doubling time estimated from digital breast tomosynthesis mammograms distinguishes invasive breast cancers from benign lesions.

OBJECTIVES: The aim of this study was to determine whether lesion size metrics on consecutive screening mammograms could predict malignant invasive carcinoma versus benign lesion outcome. METHODS: We retrospectively reviewed suspicious screen-detected lesions confirmed by biopsy to be invasive breast cancers or benign that were visible on current and in-retrospect prior screening mammograms performed with digital breast tomosynthesis from 2017 to 2020. Four experienced radiologists recorded mammogram dates, breast density, lesion type, lesion diameter, and morphology on current and prior exams. We used logistic regression models to evaluate the association of invasive breast cancer outcome with lesion size metrics such as maximum dimension, average dimension, volume, and tumor volume doubling time (TVDT). RESULTS: Twenty-eight patients with invasive ductal carcinoma or invasive lobular carcinoma and 40 patients with benign lesions were identified. The mean TVDT was significantly shorter for invasive breast cancers compared to benign lesions (0.84 vs. 2.5 years; p = 0.0025). Patients with a TVDT of less than 1 year were shown to have an odds ratio of invasive cancer of 6.33 (95% confidence interval, 2.18-18.43). Logistic regression adjusted for age, lesion maximum dimension, and lesion volume demonstrated that shorter TVDT was the size variable significantly associated with invasive cancer outcome. CONCLUSION: Invasive breast cancers detected on current and in-retrospect prior screening mammograms are associated with shorter TVDT compared to benign lesions. If confirmed to be sufficiently predictive of benignity in larger studies, lesions visible on mammograms which in comparison to prior exams have longer TVDTs could potentially avoid additional imaging and/or biopsy. KEY POINTS: • We propose tumor volume doubling time as a measure to distinguish benign from invasive breast cancer lesions. • Logistic regression results summarized the utility of the odds ratio in retrospective clinical mammography data.

Impact of Coronavirus Disease 2019 Restrictions on Retinal Detachment: A Multicenter Experience.

In this retrospective, multicenter study of 261 eyes (259 patients), patients who underwent rhegmatogenous retinal detachment repair during the coronavirus disease 2019 (COVID-19) post-lockdown period experienced an additional 22-day delay, leading to significantly more epiretinal membrane and proliferative vitreoretinopathy and lower single-surgery anatomic success rates. During lockdown, perfluoropropane gas was used more commonly, and pneumatic retinopexy was used more commonly in COVID-19-positive patients.

Mentorship Interest in Breast Imaging: Survey Results From the Society of Breast Imaging.

OBJECTIVE: This study assessed mentorship interest within the breast radiologist community to guide development of a mentorship program through the Society of Breast Imaging (SBI). METHODS: A 19-question survey developed by the SBI mentorship committee was distributed electronically to its members March 16, 2021, to May 7, 2021, to gauge interest in forming a society-sponsored mentorship program. Responses were analyzed, with subgroups compared using chi-square analysis. RESULTS: There was an 18% response rate (598/3277), and 65% (381/588) professed interest in an SBI-sponsored mentorship. Respondents were evenly distributed between academic (241/586, 41%) and private practice (242/586, 41%). Most were breast imaging fellowship-trained (355/593, 60%) and identified as female (420/596, 70%). For practice years, 50% (293/586) were late career (11+ years) with the remainder early-mid career (201/586, 34%) or trainees (92/586, 16%). For mentorship content areas, work/life balance was the most popular choice (275/395, 70%) followed by leadership (234/395, 59%). Most respondents were not currently mentors (279/377, 74%) or mentees (284/337, 84%). Those interested in a mentorship relationship were statistically younger (<45 years old, 234/381, 61% vs 31/207, 15%, P < 0.00001), female (289/381, 76% vs 123/207, 59%, P = 0.00003), academics (189/381, 50% vs 48/207, 23%, P < 0.00001), identified as a racial/ethnic minority (138/381, 64% vs 121/297, 15%, P < 0.00001), and fellowship-trained (262/381, 69% vs 88/207, 43%, P < 0.00001). CONCLUSION: There is demand, especially among the society's young and minority members, for an SBI-sponsored mentorship program. Work/life balance and leadership were the most popular choices for guidance.

Breast Density Legislation Impact on Breast Cancer Screening and Risk Assessment.

OBJECTIVE: To evaluate breast density notification legislation (BDNL) on breast imaging practice patterns, risk assessment, and supplemental screening. METHODS: A 20-question anonymous web-based survey was administered to practicing Society of Breast Imaging radiologists in the U.S. between February and April 2021 regarding breast cancer risk assessment, supplemental screening, and density measurements. Results were compared between facilities with and without BDNL using the two-sided Fisher's exact test. RESULTS: One hundred and ninety-seven radiologists from 41 U.S. states, with (187/197, 95%) or without (10/197, 5%) BDNL, responded. Fifty-seven percent (113/197) performed breast cancer risk assessment, and 93% (183/197) offered supplemental screening for women with dense breasts. Between facilities with or without BDNL, there was no significant difference in whether risk assessment was (P = 0.19) or was not performed (P = 0.20). There was no significant difference in supplemental screening types (P > 0.05) between BDNL and non-BDNL facilities. Thirty-five percent (69/197) of facilities offered no supplemental screening studies, and 25% (49/197) had no future plans to offer supplemental screening. A statistically significant greater proportion of non-BDNL facilities offered no supplemental screening (P < 0.03) and had no plans to offer supplemental screening compared to BDNL facilities (P < 0.02). CONCLUSION: Facilities in BDNL states often offer supplemental screening compared to facilities in non-BDNL states. Compared to BDNL facilities, a statistically significant proportion of non-BDNL facilities had no supplemental screening nor plans for implementation. Our data suggest that upcoming federal BDNL will impact how supplemental screening is addressed in currently non-BDNL states.

Cancer DEIso: An integrative analysis platform for investigating differentially expressed gene-level and isoform-level human cancer markers.

Transcript isoforms regulated by alternative splicing can substantially impact carcinogenesis, leading to a need to obtain clues for both gene differential expression and malfunctions of isoform distributions in cancer studies. The Cancer Genome Atlas (TCGA) project was launched in 2008 to collect cancer-related genome mutation raw data from the population. While many repositories tried to add insights into the raw data in TCGA, no existing database provides both comprehensive gene-level and isoform-level cancer stage marker investigation and survival analysis. We constructed Cancer DEIso to facilitate in-depth analyses for both gene-level and isoform-level human cancer studies. Patient RNA-seq data, sample sheets, patient clinical data, and human genome datasets were collected and processed in Cancer DEIso. And four functions to search differentially expressed genes/isoforms between cancer stages were implemented: (i) Search potential gene/isoform markers for a specified cancer type and its two stages; (ii) Search potentially induced cancer types and stages for a gene/isoform; (iii) Expression survival analysis on a given gene/isoform for some cancer; (iv) Gene/isoform stage expression comparison visualization. As an example, we demonstrate that Cancer DEIso can indicate potential colorectal cancer isoform diagnostic markers that are not easily detected when only gene-level expressions are considered. Cancer DEIso is available at http://cosbi4.ee.ncku.edu.tw/DEIso/.

A tool for analyzing and visualizing ribo-seq data at the isoform level.

BACKGROUND: Translational regulation is one important aspect of gene expression regulation. Dysregulation of translation results in abnormal cell physiology and leads to diseases. Ribosome profiling (RP), also called ribo-seq, is a powerful experimental technique to study translational regulation. It can capture a snapshot of translation by deep sequencing of ribosome-protected mRNA fragments. Many ribosome profiling data processing tools have been developed. However, almost all tools analyze ribosome profiling data at the gene level. Since different isoforms of a gene may produce different proteins with distinct biological functions, it is advantageous to analyze ribosome profiling data at the isoform level. To meet this need, previously we developed a pipeline to analyze 610 public human ribosome profiling data at the isoform level and constructed HRPDviewer database. RESULTS: To allow other researchers to use our pipeline as well, here we implement our pipeline as an easy-to-use software tool called RPiso. Compared to Ribomap (a widely used tool which provides isoform-level ribosome profiling analyses), our RPiso (1) estimates isoform abundance more accurately, (2) supports analyses on more species, and (3) provides a web-based viewer for interactively visualizing ribosome profiling data on the selected mRNA isoforms. CONCLUSIONS: In this study, we developed RPiso software tool ( http://cosbi7.ee.ncku.edu.tw/RPiso/ ) to provide isoform-level ribosome profiling analyses. RPiso is very easy to install and execute. RPiso also provides a web-based viewer for interactively visualizing ribosome profiling data on the selected mRNA isoforms. We believe that RPiso is a useful tool for researchers to analyze and visualize their own ribosome profiling data at the isoform level.

Extracellular Vesicle miR-200c Enhances Gefitinib Sensitivity in Heterogeneous EGFR-Mutant NSCLC.

Intratumoral heterogeneity in epidermal growth factor receptor (EGFR)-mutant mutant non-small-cell lung cancer (NSCLC) explains the mixed responses to EGFR-tyrosine kinase inhibitors (TKIs). However, some studies showed tumors with low abundances of EGFR mutation still respond to EGFR-TKI, and the mechanism remained undetermined. Extracellular vesicles (EVs) can transmit antiapoptotic signals between drug-resistant and drug-sensitive cells. Herein, we profiled EVs from EGFR-mutant cells to identify a novel mechanism explaining why heterogenous EGFR-mutant NSCLC patients still respond to EGFR-TKIs. We first demonstrated that the EVs from EGFR-mutant changes the wild-type cells' sensitivity to gefitinib by adding EV directly or coculturing EGFR wild-type (CL1-5) cells and EGFR-mutant (PC9) cells. In animal studies, only the combined treatment of PC9 EV and gefitinib delayed the tumor growth of CL1-5 cells. MicroRNA analysis comparing EV miRNAs from PC9 cells to those from CL1-5 cells showed that mir200 family members are most abundant in PC9 EVs. Furthermore, mir200a and mir200c were found upregulated in plasma EVs from good responders to EGFR-TKIs. Finally, the transfection of CL1-5 cells with miR200c inactivates downstream signaling pathways of EGFR, the EMT pathway, and enhances gefitinib sensitivity. Overall, our results suggest that in heterogeneous EGFR-mutant NSCLC, tumor cells transmit EV miRNAs that may affect sensitivity to EGFR-TKIs and provide potential prognostic biomarkers for EGFR-mutant NSCLC.

Relationships between Follicle-Stimulating Hormone and Adiponectin in Postmenopausal Women.

Beyond fertility, follicle-stimulating hormone (FSH) may exert action on adipocytes, which are the major source of adiponectin and leptin, linking to insulin resistance. Therefore, we evaluated the relationships between FSH and adipocyte-derived hormones. This cross-sectional study enrolled postmenopausal women aged 40-65 years. The variables measured in this study included clinical parameters, fasting levels of sex hormones, glucose, insulin, and adipokines. A total of 261 women without breast cancer, 88 women with breast cancer receiving tamoxifen, and 59 women with breast cancer receiving additional gonadotropin-releasing hormone analogs were enrolled in this study. Significant differences in the levels of adiponectin, leptin, and FSH were observed between the non-breast cancer group and the breast cancer groups. Spearman's rank test revealed significant associations of FSH with either body mass index (BMI) or homeostatic model assessment of insulin resistance (HOMA-IR) values in the non-breast cancer group. After adjusting for BMI, age, and menopause duration, FSH levels were significantly associated with adiponectin (p < 0.001) and the leptin-to-adiponectin ratio (p = 0.008) in the non-breast cancer group, but they were only significantly associated with adiponectin (p = 0.001) in the breast cancer group receiving tamoxifen. Our data show that FSH levels are independently associated with adiponectin levels in postmenopausal women, suggesting that adiponectin may link FSH to metabolic relationships in postmenopausal female.

Dissecting efficiency of a 5' rapid amplification of cDNA ends (5'-RACE) approach for profiling T-cell receptor beta repertoire.

Deep sequencing of T-cell receptor (TCR) genes is powerful at profiling immune repertoire. To prepare a TCR sequencing library, multiplex polymerase chain reaction (mPCR) is widely applied and is highly efficient. That is, most mPCR products contain the region critical for antigen recognition, which also indicates regular V(D)J recombination. Multiplex PCR, however, may suffer from primer bias. A promising alternative is 5'-RACE, which avoids primer bias by applying only one primer pair. In 5'-RACE data, however, non-regular V(D)J recombination (e.g., TCR sequences without a V gene segment) has been observed and the frequency varies (30-80%) between studies. This suggests that the cause of or how to reduce non-regular TCR sequences is not yet well known by the science community. Although it is possible to speculate the cause by comparing the 5'-RACE protocols, careful experimental confirmation is needed and such a systematic study is still not available. Here, we examined the 5'-RACE protocol of a commercial kit and demonstrated how a modification increased the fraction of regular TCR-ß sequences to >85%. We also found a strong linear correlation between the fraction of short DNA fragments and the percentage of non-regular TCR-ß sequences, indicating that the presence of short DNA fragments in the library was the main cause of non-regular TCR-ß sequences. Therefore, thorough removal of short DNA fragments from a 5'-RACE library is the key to high data efficiency. We highly recommend conducting a fragment length analysis before sequencing, and the fraction of short DNA fragments can be used to estimate the percentage of non-regular TCR sequences. As deep sequencing of TCR genes is still relatively expensive, good quality control should be valuable.

TIAM2S Mediates Serotonin Homeostasis and Provokes a Pro-Inflammatory Immune Microenvironment Permissive for Colorectal Tumorigenesis.

The short isoform of human TIAM2 has been shown to promote proliferation and invasion in various cancer cells. However, the roles of TIAM2S in immune cells in relation to tumor development have not been investigated. To characterize the effects of TIAM2S, we generated TIAM2S-overexpressing mouse lines and found that aged TIAM2S-transgenic (TIAM2S-TG) developed significantly higher occurrence of lymphocytic infiltration and tumorigenesis in various organs, including colon. In addition, TIAM2S-TG is more sensitized to AOM-induced colon tumor development, suggesting a priming effect toward tumorigenesis. In the light of our recent findings that TIAM2S functions as a novel regulator of cellular serotonin level, we found that serotonin, in addition to Cox2, is a unique inflammation marker presented in the colonic lesion sites in the aged TG animals. Furthermore, our results demonstrated that ectopic TIAM2S altered immunity via the expansion of T lymphocytes; this was especially pronounced in CD8+ T cells in combination with CXCL13/BCA-1 pro-inflammatory chemokine in the serum of TIAM2S-TG mice. Consequently, T lymphocytes and B cells were recruited to the lesion sites and stimulated IL-23/IL17A expression to form the tertiary lymphoid organs. Collectively, our research suggests that TIAM2S provokes a pro-inflammatory immune microenvironment permissive to colorectal tumorigenesis through the serotonin-induced immunomodulatory effects.

Eyelid retraction discomfort with cotton-tipped applicator, unimanual and speculum intravitreal injection techniques: Eyelid retraction technique randomized comparison trial (Eyelid RETRACT).

Purpose: The aim of this study was to test the discomfort experienced during intravitreal injections with eyelid retraction between an eyelid speculum, cotton-tipped applicator (CTA), and unimanual eyelid retraction techniques. Methods: In total, 99 patients receiving intravitreal bevacizumab were enrolled into this prospective study. Participants were randomized to one of the three methods, given subconjunctival 2% lidocaine and then injected in the superior temporal quadrant. Immediately after the procedure, each patient was given a visual analog scale (VAS) to rate their discomfort. Results: The mean pain scores for eyelid retraction with unimanual, CTA, and speculum groups were 0.788 (standard deviation [SD] 0.70, 95% confidence interval [CI] 0.448-1.128), 0.945 (SD 1.28, 95% CI 0.600-1.291), and 1.561 (SD 1.28, 95% CI 1.210-1.912), respectively. A one-way analysis of variance (ANOVA) test revealed a significant difference between the groups (P = 0.006). Post hoc analysis also revealed a difference in mean pain scores between the speculum and both the CTA and the unimanual methods. Conclusion: Our study shows that the unimanual and CTA methods for eyelid retraction are significantly less painful for patients compared to the speculum method. Patient comfort is of the utmost importance as intravitreal injections are performed millions of times a year with most patients requiring multiple injections.

mRNAsi Index: Machine Learning in Mining Lung Adenocarcinoma Stem Cell Biomarkers.

Cancer stem cells (CSCs), characterized by self-renewal and unlimited proliferation, lead to therapeutic resistance in lung cancer. In this study, we aimed to investigate the expressions of stem cell-related genes in lung adenocarcinoma (LUAD). The stemness index based on mRNA expression (mRNAsi) was utilized to analyze LUAD cases in the Cancer Genome Atlas (TCGA). First, mRNAsi was analyzed with differential expressions, survival analysis, clinical stages, and gender in LUADs. Then, the weighted gene co-expression network analysis was performed to discover modules of stemness and key genes. The interplay among the key genes was explored at the transcription and protein levels. The enrichment analysis was performed to annotate the function and pathways of the key genes. The expression levels of key genes were validated in a pan-cancer scale. The pathological stage associated gene expression level and survival probability were also validated. The Gene Expression Omnibus (GEO) database was additionally used for validation. The mRNAsi was significantly upregulated in cancer cases. In general, the mRNAsi score increases according to clinical stages and differs in gender significantly. Lower mRNAsi groups had a better overall survival in major LUADs, within five years. The distinguished modules and key genes were selected according to the correlations to the mRNAsi. Thirteen key genes (CCNB1, BUB1, BUB1B, CDC20, PLK1, TTK, CDC45, ESPL1, CCNA2, MCM6, ORC1, MCM2, and CHEK1) were enriched from the cell cycle Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, relating to cell proliferation Gene Ontology (GO) terms, as well. Eight of the thirteen genes have been reported to be associated with the CSC characteristics. However, all of them have been previously ignored in LUADs. Their expression increased according to the pathological stages of LUAD, and these genes were clearly upregulated in pan-cancers. In the GEO database, only the tumor necrosis factor receptor associated factor-interacting protein (TRAIP) from the blue module was matched with the stemness microarray data. These key genes were found to have strong correlations as a whole, and could be used as therapeutic targets in the treatment of LUAD, by inhibiting the stemness features.

Readability Assessment of Online Uveitis Patient Education Materials.

Purpose: To evaluate the readability of online uveitis patient education materials. Methods: A Google search in November 2016 was completed using search term "uveitis" and "uveitis inflammation." The top 50 websites with patient-centered information were selected and analyzed for readability using the Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES), Gunning FOG Index (GFI), and Simple Measure of Gobbledygook (SMOG). Statistical analysis was performed with two-tailed t-tests. Results: The mean word count of the top 50 websites was 1162.7 words, and averaged 16.2 words per sentence. For these websites, the mean FRES was 38.0 (range 4-66, SD = 12.0), mean FKGL was 12.3 (range 6.8-19, SD = 2.4), mean SMOG score was 14.4 (range 9.8-19, SD = 1.8), and the mean Gunning FOG index was 14.0 (range 8.6-19, SD = 2.0). Conclusions: The majority of online patient directed uveitis materials are at a higher reading level than that of the average American adult.

HRPDviewer: human ribosome profiling data viewer.

Translational regulation plays an important role in protein synthesis. Dysregulation of translation causes abnormal cell physiology and leads to diseases such as inflammatory disorders and cancers. An emerging technique, called ribosome profiling (ribo-seq), was developed to capture a snapshot of translation. It is based on deep sequencing of ribosome-protected mRNA fragments. A lot of ribo-seq data have been generated in various studies, so databases are needed for depositing and visualizing the published ribo-seq data. Nowadays, GWIPS-viz, RPFdb and TranslatomeDB are the three largest databases developed for this purpose. However, two challenges remain to be addressed. First, GWIPS-viz and RPFdb databases align the published ribo-seq data to the genome. Since ribo-seq data aim to reveal the actively translated mRNA transcripts, there are advantages of aligning ribo-req data to the transcriptome over the genome. Second, TranslatomeDB does not provide any visualization and the other two databases only provide visualization of the ribo-seq data around a specific genomic location, while simultaneous visualization of the ribo-seq data on multiple mRNA transcripts produced from the same gene or different genes is desired. To address these two challenges, we developed the Human Ribosome Profiling Data viewer (HRPDviewer). HRPDviewer (i) contains 610 published human ribo-seq datasets from Gene Expression Omnibus, (ii) aligns the ribo-seq data to the transcriptome and (iii) provides visualization of the ribo-seq data on the selected mRNA transcripts. Using HRPDviewer, researchers can compare the ribosome binding patterns of multiple mRNA transcripts from the same gene or different genes to gain an accurate understanding of protein synthesis in human cells. We believe that HRPDviewer is a useful resource for researchers to study translational regulation in human.Database URL: http://cosbi4.ee.ncku.edu.tw/HRPDviewer/ or http://cosbi5.ee.ncku.edu.tw/HRPDviewer/.

Intravenous Drug Use-Associated Scopulariopsis Endophthalmitis Treated with Systemic and Intravitreal Voriconazole.

PURPOSE: To report a case of intravenous (i.v.) heroin use-associated endogenous endophthalmitis caused by Scopulariopsis fungal species, and its response to intravitreal and oral voriconazole treatments. PATIENT: A 21-year-old-female with chronic hepatitis C and i.v. heroin use presented with subacute decreased vision to hand motion in her left eye. RESULTS: Endogenous fungal endophthalmitis caused by Scopulariopsis was confirmed by vitreous biopsy. The patient improved clinically after vitrectomy with intravitreal voriconazole and 3 weeks of oral voriconazole. The final vision was 20/60 after 6 months. CONCLUSIONS: Scopulariopsis is a rare cause of endophthalmitis, and is often difficult to treat due to its resistance to commonly used antifungals. This case is the first report of Scopulariopsis endophthalmitis secondary to i.v. drug use.

Structured Reporting of Multiphasic CT for Hepatocellular Carcinoma: Effect on Staging and Suitability for Transplant.

OBJECTIVE: The purpose of this study is to evaluate whether use of a standardized radiology report template would improve the ability of liver transplant surgeons to diagnose stage T2 hepatocellular carcinoma (HCC) and determine patient suitability to undergo orthotopic liver transplant (OLT). MATERIALS AND METHODS: In this retrospective study, a standardized template was devised, and its use was mandated for reporting of liver CT findings for patients with cirrhosis and HCC. Two surgeons analyzed 200 reports (100 before and 100 after template implementation) for descriptions of cirrhosis, portal hypertension, lesion enhancement characteristics, tumor thrombus, portal and superior mesenteric vein patency, and Organ Procurement Transplantation Network (OPTN) class. Ability to determine Milan criteria and surgeon satisfaction were also assessed. Data obtained before and after template implementation were statistically analyzed using the Cochran-Mantel-Haenszel test. RESULTS: Template implementation increased the percentage of reports documenting the presence or absence of portal hypertension (74% to 88% for surgeon 1 and 86% to 87% for surgeon 2; p = 0.042); lesion number (76% to 88% for surgeon 2 [no change for surgeon 1]; p = 0.038), size (95% to 96% for surgeon 1 and 82% to 93% for surgeon 2; p = 0.03), and enhancement (93% to 94% for surgeon 1 and 80% to 91% for surgeon 2; p = 0.049); presence of tumor thrombus (10% to 57% for surgeon 1 and 31% to 63% for surgeon 2; p < 0.001); and OPTN class (8% to 82% for surgeon 1 and 2% to 81% for surgeon 2; p < 0.001). The surgeons were significantly more able to determine the presence of T2 disease and qualification for exception points after implementation of the template (increasing from 80% to 94%; p = 0.025). Satisfaction with reports also improved (p < 0.0001). CONCLUSION: The reporting template improved determination of patient suitability to undergo transplant according to the Milan criteria.

CSmiRTar: Condition-Specific microRNA targets database.

MicroRNAs (miRNAs) are functional RNA molecules which play important roles in the post-transcriptional regulation. miRNAs regulate their target genes by repressing translation or inducing degradation of the target genes' mRNAs. Many databases have been constructed to provide computationally predicted miRNA targets. However, they cannot provide the miRNA targets expressed in a specific tissue and related to a specific disease at the same time. Moreover, they cannot provide the common targets of multiple miRNAs and the common miRNAs of multiple genes at the same time. To solve these two problems, we construct a database called CSmiRTar (Condition-Specific miRNA Targets). CSmiRTar collects computationally predicted targets of 2588 human miRNAs and 1945 mouse miRNAs from four most widely used miRNA target prediction databases (miRDB, TargetScan, microRNA.org and DIANA-microT) and implements functional filters which allows users to search (i) a miRNA's targets expressed in a specific tissue or/and related to a specific disease, (ii) multiple miRNAs' common targets expressed in a specific tissue or/and related to a specific disease, (iii) a gene's miRNAs related to a specific disease, and (iv) multiple genes' common miRNAs related to a specific disease. We believe that CSmiRTar will be a useful database for biologists to study the molecular mechanisms of post-transcriptional regulation in human or mouse. CSmiRTar is available at http://cosbi.ee.ncku.edu.tw/CSmiRTar/ or http://cosbi4.ee.ncku.edu.tw/CSmiRTar/.

Medroxyprogesterone acetate drives M2 macrophage differentiation toward a phenotype of decidual macrophage.

M1 macrophage differentiation plays a crucial role in enhanced inflammation during pregnancy, which may lead to pregnancy complications. Therefore, modulation of macrophage differentiation toward the M2 phenotype is desirable to ensure a successful pregnancy. Medroxyprogesterone acetate (MPA) is a potent progestin with an anti-inflammatory property, but its effect on macrophage differentiation is unknown. This study aimed to examine whether MPA can induce an M2 macrophage differentiation by using the human monocytes cell line THP-1 or primary monocytes. THP-1 cells were primed with phorbol-12-myristate-13 acetate (PMA) to initiate macrophage differentiation. By incubating with MPA, the cells (denoted as MPA-pTHP-1) underwent M2 macrophage differentiation with downregulations of CD11c, IL-1ß and TNF-α, and upregulations of CD163 and IL-10; while cells incubated with progesterone (P4) did not show the M2 phenotype. Primary monocytes treated with MPA also had the same M2 phenotype. Moreover, M1 macrophages derived from IFN-γ/LPS-treated THP-1 cells, which had high levels of IL-1b and iNOS, and low levels of IL-10 and IDO, were reversed to the M2 phenotype by the MPA treatment. We also found that the MPA-pTHP-1 promoted the decidualization of endometrial stromal cells and the invasion of trophoblast cells. To mimic conditions of exposure to various pathogens, MPA-pTHP-1 cells were stimulated by different types of TLR ligands. We found they produced lower levels of IL-1ß and TNF-α, as well as a higher level of IL-10, compared to untreated cells. Finally, we found the level of phosphorylated ERK in the MPA-pTHP-1 cells was increased, but its IL-10 production was suppressed by either the progesterone/glucocorticoid antagonist (Mifepristone) or MEK inhibitor (U0126). Taken together, MPA could drive monocyte differentiation toward an M2 phenotype that mimics decidual macrophages. This finding holds great potential to combat chronic endometrial inflammation.

Translational upregulation of Aurora-A by hnRNP Q1 contributes to cell proliferation and tumorigenesis in colorectal cancer.

By using RNA-immunoprecipitation assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnRNP Q1 can upregulate Aurora-A protein, but not alter the mRNA level, through enhancing the translational efficiency of Aurora-A mRNA, either in a cap-dependent or -independent manner, by interacting with the 5'-UTR of Aurora-A mRNA through its RNA-binding domains (RBDs) 2 and 3. By ribosomal profiling assay further confirmed the translational regulation of Aurora-A mRNA by hnRNP Q1. Overexpression of hnRNP Q1 promotes cell proliferation and tumor growth. HnRNP Q1/ΔRBD23-truncated mutant, which loses the binding ability and translational regulation of Aurora-A mRNA, has no effect on promoting tumor growth. The expression level of hnRNP Q1 is positively correlated with Aurora-A in colorectal cancer. Taken together, our data indicate that hnRNP Q1 is a novel trans-acting factor that binds to Aurora-A mRNA 5'-UTRs and regulates its translation, which increases cell proliferation and contributes to tumorigenesis in colorectal cancer.