Development of a Predictive Model for Optimization of Embryo Transfer Timing Using Blood-Based microRNA Expression Profile.

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.

Identification of a Common Epitope in Nucleocapsid Proteins of Euro-America Orthotospoviruses and Its Application for Tagging Proteins.

The NSs protein and the nucleocapsid protein (NP) of orthotospoviruses are the major targets for serological detection and diagnosis. A common epitope of KFTMHNQIF in the NSs proteins of Asia orthotospoviruses has been applied as an epitope tag (nss-tag) for monitoring recombinant proteins. In this study, a monoclonal antibody TNP MAb against the tomato spotted wilt virus (TSWV) NP that reacts with TSWV-serogroup members of Euro-America orthotospoviruses was produced. By truncation and deletion analyses of TSWV NP, the common epitope of KGKEYA was identified and designated as the np sequence. The np sequence was successfully utilized as an epitope tag (np-tag) to monitor various proteins, including the green fluorescence protein, the coat protein of the zucchini yellow mosaic virus, and the dust mite chimeric allergen Dp25, in a bacterial expression system. The np-tag was also applied to investigate the protein-protein interaction in immunoprecipitation. In addition, when the np-tag and the nss-tag were simultaneously attached at different termini of the expressed recombinant proteins, they reacted with the corresponding MAbs with high sensitivity. Here, we demonstrated that the np sequence and TNP MAb can be effectively applied for tagging and detecting proteins and can be coupled with the nss-tag to form a novel epitope-tagging system for investigating protein-protein interactions.

2020 Consensus Statement of the Taiwan Hypertension Society and the Taiwan Society of Cardiology on Home Blood Pressure Monitoring for the Management of Arterial Hypertension.

To facilitate the applications of home blood pressure (HBP) monitoring in clinical settings, the Taiwan Hypertension Society and the Taiwan Society of Cardiology jointly put forward the Consensus Statement on HBP monitoring according to up-to-date scientific evidence by convening a series of expert meetings and compiling opinions from the members of these two societies. In this Consensus Statement as well as recent international guidelines for management of arterial hypertension, HBP monitoring has been implemented in diagnostic confirmation of hypertension, identification of hypertension phenotypes, guidance of anti-hypertensive treatment, and detection of hypotensive events. HBP should be obtained by repetitive measurements based on the " 722 " principle, which is referred to duplicate blood pressure readings taken per occasion, twice daily, over seven consecutive days. The " 722" principle of HBP monitoring should be applied in clinical settings, including confirmation of hypertension diagnosis, 2 weeks after adjustment of antihypertensive medications, and at least every 3 months in well-controlled hypertensive patients. A good reproducibility of HBP monitoring could be achieved by individuals carefully following the instructions before and during HBP measurement, by using validated BP devices with an upper arm cuff. Corresponding to office BP thresholds of 140/90 and 130/80 mmHg, the thresholds (or targets) of HBP are 135/85 and 130/80 mmHg, respectively. HBP-based hypertension management strategies including bedtime dosing (for uncontrolled morning hypertension), shifting to drugs with longer-acting antihypertensive effect (for uncontrolled evening hypertension), and adding another antihypertensive drug (for uncontrolled morning and evening hypertension) should be considered. Only with the support from medical caregivers, paramedical team, or tele- monitoring, HBP monitoring could reliably improve the control of hypertension.

Suppression of Propionibacterium acnes-stimulated proinflammatory cytokines by Chinese bayberry extracts and its active constituent myricetin in human sebocytes in vitro.

Myrica rubra Sieb. et Zucc. (Myricaceae), known as Chinese bayberry, is traditionally used as folk medicine in Asian countries. The interaction of Propionibacterium acnes signalling with sebocytes is considered important in the pathogenesis of acne. In the present study, extracts and active compounds of Chinese bayberry were used to determine chemical antioxidant activity and anti-inflammatory effects in P. acnes-stimulated human SZ95 sebocytes. A high-performance liquid chromatography with electrochemical detection system was used to analyse the phenolic composition of bayberry extracts. Accordingly, the flavonols, myricitrin and myricetin, were found to be abundant in the unhydrolysed and hydrolysed extracts of Chinese bayberry fruits, respectively. The anthocyanin cyanidin-3-glucoside was also predominantly found in the unhydrolysed extracts. Quantification of human inflammatory cytokines indicated that cell-free extracts of P. acnes stimulated IL-8 and IL-6 production, which was inhibited by myricetin, rather than its glycoside or anthocyanin. Myricetin also exhibited inhibitory effects in P. acnes-stimulated gene expression of Toll-like receptor (TLR) 2 and protein phosphorylation of p70 S6 kinase. In conclusion, myricetin shows a suppressive effect on P. acnes-induced cytokine production through regulation of the TLR and mammalian target of rapamycin pathways. Myricetin goes beyond previous research findings to potentially modulate inflammatory signalling in human sebocytes. These results will be valuable in developing anti-inflammatory agents against skin acne.

In-Hospital Implementation of Evidence-Based Medications is Associated with Improved Survival in Diabetic Patients with Acute Coronary Syndrome - Data from TSOC ACS-DM Registry.

BACKGROUND: Patients with acute coronary syndrome (ACS) and diabetes mellitus (DM) receive less aggressive treatment and have worse outcomes in Taiwan. We sought to explore whether the current practices of prescribing guideline-directed medical therapy (GDMT) for ACS and clinical outcomes have improved over time. METHODS: A total of 1534 consecutive diabetic patients with ACS were enrolled between 2013 and 2015 from 27 hospitals in the nationwide registry initiated by the Taiwan Society of Cardiology (the TSOC ACS-DM Registry). Baseline and clinical demographics, treatment, and clinical outcomes were compared to those of 1000 ACS patients with DM recruited in the Taiwan ACS-full spectrum (ACS-FS) Registry, which was performed between 2008 and 2010. RESULTS: Compared to the DM patients in the Taiwan ACS-FS Registry, even though reperfusion therapy was carried out in significantly fewer patients, the primary percutaneous coronary intervention (PCI) rate for ST-segment elevation myocardial infarction (STEMI) and the prescription rates of GDMT for ACS including P2Y12 inhibitors, renin-angiotensin blockers, beta-blockers, and statins were significantly higher in those in the TSOC ACS-DM Registry. Moreover, significant reductions in 1-year mortality, recurrent nonfatal MI and stroke were observed compared to those of the DM patients in the Taiwan ACS-FS Registry. Multivariate analysis identified reperfusion therapy in combination with GDMT as a strong predictor of better 1-year outcomes [hazard ratio (95% confidence interval) = 0.54 (0.33-0.89)]. CONCLUSIONS: Marked improvements in performing primary PCI for STEMI and prescribing GDMT for ACS were observed over time in Taiwan. This was associated with improved 1-year event-free survival in the diabetic patients with ACS.

In-Hospital Tele-ECG Triage and Interventional Cardiologist Activation of the Infarct Team for STEMI Patients is Associated with Improved Late Clinical Outcomes.

BACKGROUND: Due to recent advances, door-to-balloon time (D2BT) has been reduced significantly for patients with ST-segment elevation myocardial infarction (STEMI). However, whether this reduction can be translated into a concrete mortality or morbidity benefit is still the subject of controversy. We conducted a before-and-after study to determine the impact of in-hospital tele-electrocardiography (ECG) triage and interventional cardiologist activation of the infarct team on D2BT and long-term clinical outcomes in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: A total of 272 consecutive patients with acute STEMI undergoing PPCI were enrolled in our study, comprising 102 tele-ECG patients and 170 conventional triage patients. Major adverse cardiovascular and cerebral vascular events (MACCE), including death, recurrent nonfatal MI, nonfatal stroke, and angina-driven target vessel revascularization were recorded during a 3-year follow-up. RESULTS: The median D2BT of the tele-ECG group was significantly shorter than control group (79 minutes vs. 109 minutes, p < 0.001). The tele-ECG triage group had a higher percentage of patients reaching the D2BT goal (< 90 minutes) (78% vs. 55%; p < 0.001). The MACCE rate was significantly lower in the Tele-ECG versus the control group (23.5% vs. 38.2%, p = 0.012). Tele-ECG group had a lower mortality rate which did not reached statistical significance (2% vs. 5.9%, p = 0.102). In multivariable Cox proportional hazards analyses, the implementation of tele-ECG triage (HR = 0.43, p = 0.003) and the presence of moderate or severe mitral regurgitation at presentation (HR = 1.87, p = 0.029) were discovered as independently associated with MACCE. CONCLUSIONS: In-hospital tele-ECG triage and interventional cardiologist activation can shorten D2BT and is associated with improved late clinical outcomes during a 3-year follow-up in STEMI patients undergoing PPCI.

Organic ultraviolet filters regulate hyaluronan metabolism in human epidermal keratinocytes through the phosphatidylinositol 3-kinase pathway.

Chronic exposure of skin to ultraviolet (UV) radiation is responsible for skin ageing, which includes degradation of the epidermal and dermal layers. Filtering UV light is key in the sunscreen industry. We studied the effects of organic UV filters on hyaluronan (HA) metabolism and skin hydration in human HaCaT keratinocytes. The gene expression of HA receptors, HA synthase (HAS), hyaluronidase (HYAL), and water channel aquaporin 3 (AQP3) was evaluated by quantitative RT-PCR. The state of oxidative stress was determined by measuring the intracellular levels of reactive oxygen species (ROS). The results showed that five organic UV filters reduced the extracellular contents of HA, and a phosphatidylinositol 3-kinase (PI3K) inhibitor partially restored the decreased HA levels after octinoxate, octocrylene, and oxybenzone treatment. The expression levels of HA receptors, including cluster of differentiation 44 (CD44), receptor for hyaluronic acid-mediated motility (RHAMM), and toll-like receptors (TLRs), were determined. Avobenzone, octinoxate, oxybenzone, and padimate O exerted inhibitory effects on RHAMM expression. Oxybenzone led to a significant increase in CD44 and AQP3 expression. Both octinoxate and octocrylene increased TLR4 expression but decreased ROS accumulation by activating the PI3K pathway. However, the organic UV filters differentially regulated the mRNA expression of HAS and HYAL. Taken together, these results suggest that certain organic UV filters regulate HA metabolism in human keratinocytes in a PI3K pathway-dependent manner.

The optical research progress of nanophosphors composed of transition elements in the fourth period of near-infrared windows I and II for deep-tissue theranostics.

Research in the field of nano-optics is advancing by leaps and bounds, among which near-infrared (NIR) light optics have attracted much attention. NIR light has a longer wavelength than visible light, such that it can avoid shielding caused by biological tissues. This advantage has driven its importance and practicality in human treatment applications and has attracted significant attention from researchers in academia and industry. In the broad spectrum of infrared light wavelengths, the most noticeable ones are the NIR biological window I of 700-900 nm and window II of 1000-1700 nm. Luminescent materials can effectively cover the NIR biological window with different doping strategies. These doped elements are mostly transition elements with multielectron orbitals. Several nanomaterials based on narrow-spectrum lanthanides have been developed to correspond to biological applications of different wavelengths. However, this review explicitly introduces the absorption and reflection/luminescence interactions between NIR light and biological tissues independently. Unlike the adjustment of the wavelength of the lanthanide series, this review analyzes the NIR optical properties of the fourth-period element ions in transition elements (such as Cr3+ and Ni2+). These elements have a broadband wavelength of NIR light emission and higher quantum efficiency, corresponding to the absorption and emission spectrum and photobiological absorption of different NIR windows for therapeutic diagnosis. Finally, this review lists and explores other broadband NIR phosphors and has tried to discover the possibility of non-invasive precision medicine in the future.

Molecular evolution of a viral non-coding sequence under the selective pressure of amiRNA-mediated silencing.

Plant microRNAs (miRNA) guide cleavage of target mRNAs by DICER-like proteins, thereby reducing mRNA abundance. Native precursor miRNAs can be redesigned to target RNAs of interest, and one application of such artificial microRNA (amiRNA) technology is to generate plants resistant to pathogenic viruses. Transgenic Arabidopsis plants expressing amiRNAs designed to target the genome of two unrelated viruses were resistant, in a highly specific manner, to the appropriate virus. Here, we pursued two different goals. First, we confirmed that the 21-nt target site of viral RNAs is both necessary and sufficient for resistance. Second, we studied the evolutionary stability of amiRNA-mediated resistance against a genetically plastic RNA virus, TuMV. To dissociate selective pressures acting upon protein function from those acting at the RNA level, we constructed a chimeric TuMV harboring a 21-nt, amiRNA target site in a non-essential region. In the first set of experiments designed to assess the likelihood of resistance breakdown, we explored the effect of single nucleotide mutation within the target 21-nt on the ability of mutant viruses to successfully infect amiRNA-expressing plants. We found non-equivalency of the target nucleotides, which can be divided into three categories depending on their impact in virus pathogenicity. In the second set of experiments, we investigated the evolution of the virus mutants in amiRNA-expressing plants. The most common outcome was the deletion of the target. However, when the 21-nt target was retained, viruses accumulated additional substitutions on it, further reducing the binding/cleavage ability of the amiRNA. The pattern of substitutions within the viral target was largely dominated by G to A and C to U transitions.

Transradial approach in myocardial infarction.

OBJECTIVE: This study investigates the feasibility, efficacy, and safety of routine primary percutaneous coronary intervention via transradial approach in patients with acute ST-elevation myocardial infarction. METHODS AND RESULTS: From 2005 to 2007,122 consecutive patients with acute ST-elevation myocardial infarction within 12 hours, including those experiencing cardiogenic shock, were eligible for primary transradial PCI if the radial artery pulse could be felt. Efficacy, safety, and major adverse cardiac events regarding mortality, recurrent non-fatal myocardial infarction, and revascularization were recorded. Eighty-five of 122 patients underwent transradial PCI, and 37 had transfemoral PCI. Older women, haemodynamic instability, and the presence of severe chronic kidney disease (stages 4 and 5) or end-stage renal disease were significantly related to choice of transfemoral approach (P < 0.05). Glycoprotein IIb/IIIa inhibitors were used more often in patients who underwent transradial PCI than in those who underwent transfemoral PCI (37% vs 16%; P = 0.043). The incidence of major bleeding complications requiring blood transfusion was significantly higher in the transfemoral group (P = 0.004). A similar procedural success rate was achieved in both groups (P = 0.737). During follow-up of 580 days, the total major adverse cardiac events were similar in both groups (P = 0.299). CONCLUSIONS: Routine transradial primary PCI can be safely and successfully performed on up to 70% of acute ST-elevation myocardial infarction patients and, compared with transfemoral approach, is associated with a significantly reduced rate of major bleeding complications.

Discriminating mutations of HC-Pro of zucchini yellow mosaic virus with differential effects on small RNA pathways involved in viral pathogenicity and symptom development.

Helper component-proteinase (HC-Pro), the gene-silencing suppressor of Potyvirus spp., interferes with microRNA (miRNA) and short-interfering RNA (siRNA) pathways. Our previous studies showed that three mutations of highly conserved amino acids of HC-Pro, R(180)I (mutation A), F(205)L (B), and E(396)N (C), of Zucchini yellow mosaic virus (ZYMV) affect symptom severity and viral pathogenicity. The mutant ZYMV GAC (ZGAC) with double mutations, R(180)I/E(396)N, induces transient leaf mottling in host plants followed by recovery. This mutant confers complete cross protection against subsequent infection by the parental ZYMV (ZG) strain. Here, we sought to obtain molecular evidence on the roles of the three highly conserved amino acids of HC-Pro in miRNA and siRNA pathways using transgenic Arabidopsis plants expressing comparable levels of wild-type and mutant HC-Pro proteins. We demonstrated that amino acid residues 180, 205, and 396 of HC-Pro are critical for suppression of miRNA, trans-acting siRNA (ta-siRNA), and virus-induced gene silencing (VIGS) pathways but not for sense-post transcriptional gene silencing (s-PTGS). Because the HC-Pro double mutant (R(180)I/E(396)N) does not interfere with miRNA and ta-siRNA pathways, the ZGAC mutant virus elicits only attenuated symptoms. Furthermore, the recovery seen on ZGAC-infected plants likely results from the weak VIGS suppression by the HC-Pro double AC mutant. Thus, through manipulating these three conserved amino acids on HC-Pro, symptom severity of diseases caused by Potyvirus spp. can be modulated to generate useful cross protectants for field application. Although some of our mutated HC-Pro proteins do not interfere with miRNA and ta-siRNA pathways, they still retain the ability to suppress s-PTGS.

Recovery of left ventricular dysfunction after sacubitril/valsartan: predictors and management.

BACKGROUND: Literature describing recovery of left ventricular (LV) function post sacubitril/valsartan treatment and the optimal management of heart failure (HF) patients receiving sacubitril/valsartan remain sparse. METHODS: We recruited 437 consecutive chronic HF patients with baseline left ventricular ejection fraction (LVEF) less than 40%, who were treated with sacubitril/valsartan. All patients underwent routine echocardiographic measurement. RESULTS: During treatment period, recovery of LVEF to 50% or greater was observed in 77 (17.6%) patients. After multivariate analysis, recovery of LV dysfunction was associated with non-ischemic etiology of HF, smaller baseline LV end-diastolic diameter (LVEDD), and higher initial dosage of sacubitril/valsartan. Compared to those without recovery of LV dysfunction, death from cardiovascular causes or first unplanned hospitalization for HF (CVD/HFH) were significantly lower in patients with LVEF recovery [11.7% vs. 24.4%, hazard ratio (HR) 0.42, p = 0.014]. Among patients with recovery of LVEF, 51 patients continued to receive the same dosage of sacubitril/valsartan had higher LVEF and were less likely to have deterioration of LVEF than the other 26 patients who received either tapering dose of sacubitril/valsartan or switching from sacubitril/valsartan to renin-angiotensin-system blockers (LVEF 56.4 ± 5.3% vs. 45.0 ± 12.8%, p < 0.001; ΔLVEF 1.2 ± 5.1% vs. -9.3 ± 12.0%, p < 0.001). CVD/HFH occurred more frequently in the taper group than the maintenance group (23.1% vs. 5.9%, HR 0.22, p = 0.035). CONCLUSIONS: Non-ischemic etiology of HF, smaller baseline LVEDD, and higher initial dosage of sacubitril/valsartan could predict better recovery of LV function. Among patients with functional recovery, tapering sacubitril/valsartan dose was associated with deterioration of recovered heart function and had less favorable prognosis during follow-up.

Prescription patterns of diabetes medications influencing clinical outcomes of heart failure patients with reduced ejection fraction.

AIMS: We collected the different prescription patterns of diabetes medications in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and analysed the impact of different prescription patterns on clinical outcomes. METHODS AND RESULTS: Consecutive diabetic patients with HFrEF from a heart failure referral centre were retrospectively analysed between 2015 and 2016. Exclusion criteria include being lost to follow-up, not receiving diabetes medications, and having severe renal impairment with a glomerular filtration rate < 30 mL/min/1.73 m2 . Prescription of diabetes medications and the respective clinical outcomes were collected between 2016 and 2018. Among 381 patients (mean age, 64.8 ± 12.8 years; 71.9% male; mean left ventricular ejection fraction, 27.6 ± 7.0%; mean body mass index, 26.1 ± 4.7 kg/m2 ), the prescription rates of sodium-glucose co-transporter 2 inhibitor (SGLT2i) increased from 10.3% in 2016 to 17.6% in 2017 and 26.5% in 2018 (P < 0.001); the prescription rates of metformin, sulfonylurea, insulin, and dipeptidyl peptidase-4 inhibitors did not change significantly over time. The prescription rates of metformin and SGLT2i were significantly higher in patients managed by cardiologists than non-cardiologists (in 2018, 71.1% vs. 44.2% for metformin, 45.4% vs. 9.9% for SGLT2i, both P < 0.001). During the study period, annualized event rates of cardiovascular death or first unplanned HF hospitalization were 19.0 per 100 patient-years. After a multivariate analysis, prescriptions of metformin {odds ratio (OR): 0.49 [95% confidence interval (CI) 0.27-0.51], P < 0.001} and SGLT2i [OR: 0.52 (95% CI 0.28-0.98), P = 0.042] were independently associated with lower annualized event rates of cardiovascular death or unplanned HF hospitalization. CONCLUSIONS: Prescription patterns of diabetes medications in diabetics with HFrEF were diverse among different specialists. Prescriptions of metformin and SGLT2i were associated with favourable clinical outcomes. Our finding indicates the importance of awareness of beneficial effect of different classes of diabetes medications and collaboration between specialists in the management of diabetic HFrEF patients.

RING1 E3 ligase localizes to plasma membrane lipid rafts to trigger FB1-induced programmed cell death in Arabidopsis.

Ubiquitination plays important roles in plant development, including programmed cell death. Here, we characterize a novel membrane-bound RING motif protein, encoded by RING1, that is expressed at a low level in all Arabidopsis tissues but can be upregulated by fumonisin B1 (FB1) treatment and pathogen infection. RING1 displays E3 ubiquitin ligase activity in vitro, which is dependent on the integrity of the RING motif. GFP fusion protein localization and cell fractionation experiments show that this E3 ligase is associated with the lipid rafts of plasma membranes. Knock-down of RING1 transcripts using artificial microRNA (amiR-R1(159)) leads to FB1 hyposensitivity, but overexpression of RING1 confers hypersensitivity. Additionally, expression of the pathogenesis-related 1 (PR-1) gene is lower and delayed in amiR-R1(159) plants compared with wild-type and RING1-overexpressing plants. The FB1 hyposensitivity of amiR-R1(159) plants can be rescued by expression of cleavage-resistant RING1mut transcripts. Our results suggest that RING1 acts as a signal from the plasma membrane lipid rafts to trigger the FB1-induced plant programmed cell death pathway.

Expression of artificial microRNAs in transgenic Arabidopsis thaliana confers virus resistance.

Plant microRNAs (miRNAs) regulate the abundance of target mRNAs by guiding their cleavage at the sequence complementary region. We have modified an Arabidopsis thaliana miR159 precursor to express artificial miRNAs (amiRNAs) targeting viral mRNA sequences encoding two gene silencing suppressors, P69 of turnip yellow mosaic virus (TYMV) and HC-Pro of turnip mosaic virus (TuMV). Production of these amiRNAs requires A. thaliana DICER-like protein 1. Transgenic A. thaliana plants expressing amiR-P69(159) and amiR-HC-Pro(159) are specifically resistant to TYMV and TuMV, respectively. Expression of amiR-TuCP(159) targeting TuMV coat protein sequences also confers specific TuMV resistance. However, transgenic plants that express both amiR-P69(159) and amiR-HC-Pro(159) from a dimeric pre-amiR-P69(159)/amiR-HC-Pro(159) transgene are resistant to both viruses. The virus resistance trait is displayed at the cell level and is hereditable. More important, the resistance trait is maintained at 15 degrees C, a temperature that compromises small interfering RNA-mediated gene silencing. The amiRNA-mediated approach should have broad applicability for engineering multiple virus resistance in crop plants.

Relationship Between Body Mass Index, Antidiabetic Agents, and Midterm Mortality in Patients With Both Type 2 Diabetes Mellitus and Acute Coronary Syndrome.

Background The aim of this study was to determine the influence of various antidiabetic therapies on the relationship between body mass index and all-cause mortality in patients with diabetes mellitus and acute coronary syndrome. Methods and Results This was a prospective, observational study comprising 1193 patients diagnosed with type 2 diabetes mellitus and acute coronary syndrome. The patients were stratified into 4 body mass index categories, and their mortality rates were compared using time-dependent Cox regression analysis using normal weight (body mass index, 18.5-23.9) as the reference. Subsequently, the influence of antidiabetic therapies on the association between BMI and mortality were analyzed. Seventy-four patients (6.2%) died over 2 years of follow-up. The mortality rate was lowest in the class I obese group (3.35%) and highest in the normal-weight group (9.67%). After adjusting for covariates, class I obesity paradoxically remained significantly protective against mortality compared with normal weight (hazard ratio, 0.141; P=0.049); interaction term analysis showed that insulin therapy influenced this "obesity paradox" ( P=0.045). When the patients were stratified by insulin use, the protective effect of obesity disappeared in the insulin-treated patients but persisted in the non-insulin-treated patients. Conclusions In patients with type 2 diabetes mellitus and acute coronary syndrome, the relationship between body mass index and mortality rate is U-shaped, with class I obesity representing the nadir and normal weight the peak. The protective effect of obesity disappeared in patients treated with insulin.

A single amino acid of niapro of papaya ringspot virus determines host specificity for infection of papaya.

Most strains of Papaya ringspot virus (PRSV) belong to type W, causing severe loss on cucurbits worldwide, or type P, devastating papaya in tropical areas. While the host range of PRSV W is limited to plants of the families Chenopodiaceae and Cucuribitaceae, PRSV P, in addition, infects plants of the family Caricaceae (papaya family). To investigate one or more viral genetic determinants for papaya infection, recombinant viruses were constructed between PRSV P-YK and PRSV W-CI. Host reactions to recombinant viruses indicated that the viral genomic region covering the C-terminal region (142 residues) of NIaVPg, full NIaPro, and N-terminal region (18 residues) of NIb, is critical for papaya infection. Sequence analysis of this region revealed residue variations at position 176 of NIaVPg and positions 27 and 205 of NIaPro between type P and W viruses. Host reactions to the constructed mutants indicated that the amino acid Lys27 of NIaPro determines the host-specificity of PRSV for papaya infection. Predicted three-dimensional structures of NIaPros of parental viruses suggested that Lys27 does not affect the protease activity of NIaPro. Recovery of the infected plants from certain papaya-infecting mutants implied involvement of other viral factors for enhancing virulence and adaptation of PRSV on papaya.

MADS-Box Gene Classification in Angiosperms by Clustering and Machine Learning Approaches.

The MADS-box gene family is an important transcription factor family involved in floral organogenesis. The previously proposed ABCDE model suggests that different floral organ identities are controlled by various combinations of classes of MADS-box genes. The five-class ABCDE model cannot cover all the species of angiosperms, especially the orchid. Thus, we developed a two-stage approach for MADS-box gene classification to advance the study of floral organogenesis of angiosperms. First, eight classes of reference datasets (A, AGL6, B12, B34, BPI, C, D, and E) were curated and clustered by phylogenetic analysis and unsupervised learning, and they were confirmed by the literature. Second, feature selection and multiple prediction models were curated according to sequence similarity and the characteristics of the MADS-box gene domain using support vector machines. Compared with the BindN and COILS features, the local BLAST model yielded the best accuracy. For performance evaluation, the accuracy of Phalaenopsis aphrodite MADS-box gene classification was 93.3%, which is higher than 86.7% of our previous classification prediction tool, iMADS. Phylogenetic tree construction - the most common method for gene classification yields classification errors and is time-consuming for analysis of massive, multi-species, or incomplete sequences. In this regard, our new system can also confirm the classification errors of all the random selection that were incorrectly classified by phylogenetic tree analysis. Our model constitutes a reliable and efficient MADS-box gene classification system for angiosperms.

Coronary revascularization in a patient with immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by premature platelet destruction mediated by autoantibodies. We report a 71-year-old ITP patient with concomitant acute coronary syndrome. Cardiac catheterization was performed through the right radial artery and premedicated with immunoglobulin. Left anterior descending artery was stented, followed by clopidogrel treatment for 7 weeks without major bleeding complication. The patient has been observed for 2 years without clinical restenosis. We suggest that stent implantation is a safe treatment in this special condition. Treatment should be individualized, but it is still a challenge to balance bleeding and thrombosis complication.

The temporal trends of incidence, treatment, and in-hospital mortality of acute myocardial infarction over 15years in a Taiwanese population.

BACKGROUND: The study was conducted to examine the nationwide temporal trends of incidence, treatment, and short-term outcomes for acute myocardial infarction (AMI) over a 15-year period in Taiwan. METHODS: We identified patients who were hospitalized for incident AMI between 1997 and 2011 from the inpatient medical claim dataset of the National Health Insurance Research Database. Age- and sex-adjusted incidence and in-hospital mortality rates were calculated for AMI, and separately for ST-segment elevation and non-ST-segment elevation myocardial infarction (STEMI and NSTEMI). RESULTS: A total of 144,634 patients were identified. The incidence rates (per 100,000 population) of AMI increased from 30 in 1997 to 42 in 2011, which was mainly driven by the increase of NSTEMI. The in-hospital mortality rate after AMI decreased from 9.1% in 1997 to 6.5% in 2011, which was also driven by the case mortality rate for NSTEMI. Although the in-hospital mortality rates significantly decreased from 7.3% to 5.1% between 1997 and 2003 for STEMI, it did not change significantly from 2004 to 2011. Moreover, AMI patients undergoing revascularization treatment, particularly PCI, was the most important independent predictor for improved in-hospital survival. CONCLUSION: The results of this study demonstrated a recent dramatic increase in the incidence rates and a decrease in short-term mortality in patients with NSTEMI; while the incidence and in-hospital morality of STEMI only modestly changed over time in Taiwan. Further quality improvement approaches for AMI prevention and treatment to favorably affect the incidence and outcomes from both major types of AMI are highly recommended.