Association between triglyceride glucose-body mass index and long-term adverse outcomes of heart failure patients with coronary heart disease.

BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI) is recognized as a reliable surrogate for evaluating insulin resistance and an effective predictor of cardiovascular disease. However, the link between TyG-BMI index and adverse outcomes in heart failure (HF) patients remains unclear. This study examines the correlation of the TyG-BMI index with long-term adverse outcomes in HF patients with coronary heart disease (CHD). METHODS: This single-center, prospective cohort study included 823 HF patients with CHD. The TyG-BMI index was calculated as follows: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. To explore the association between the TyG-BMI index and the occurrences of all-cause mortality and HF rehospitalization, we utilized multivariate Cox regression models and restricted cubic splines with threshold analysis. RESULTS: Over a follow-up period of 9.4 years, 425 patients died, and 484 were rehospitalized due to HF. Threshold analysis revealed a significant reverse "J"-shaped relationship between the TyG-BMI index and all-cause mortality, indicating a decreased risk of all-cause mortality with higher TyG-BMI index values below 240.0 (adjusted model: HR 0.90, 95% CI 0.86-0.93; Log-likelihood ratio p = 0.003). A distinct "U"-shaped nonlinear relationship was observed with HF rehospitalization, with the inflection point at 228.56 (adjusted model: below: HR 0.95, 95% CI 0.91-0.98; above: HR 1.08, 95% CI 1.03-1.13; Log-likelihood ratio p < 0.001). CONCLUSIONS: This study reveals a nonlinear association between the TyG-BMI index and both all-cause mortality and HF rehospitalization in HF patients with CHD, positioning the TyG-BMI index as a significant prognostic marker in this population.

Association between age, gender, and oral traumatic ulcerative lesions: a retrospective study.

BACKGROUND: Oral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies. METHODS: A total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL. RESULTS: The study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL. CONCLUSION: The clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.

Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

Diagnostic Performance of Angiography-Derived Quantitative Flow Ratio in Complex Coronary Lesions.

BACKGROUND: Quantitative flow ratio derived from computed tomography angiography (CT-QFR) and invasive coronary angiography (Murray law-based quantitative flow ratio [µQFR]) are novel approaches enabling rapid computation of fractional flow reserve without the use of pressure guidewires and vasodilators. However, the feasibility and diagnostic performance of both CT-QFR and µQFR in evaluating complex coronary lesions remain unclear. METHODS: Between September 2014 and September 2021, 240 patients with 30% to 90% coronary diameter stenosis who underwent both coronary computed tomography angiography and invasive coronary angiography with fractional flow reserve within 60 days were retrospectively enrolled. The diagnostic performance of CT-QFR and µQFR in detecting functional ischemia among all lesions, especially complex coronary lesions, was analyzed using fractional flow reserve as the reference standard. RESULTS: CT-QFR and µQFR analyses were performed on 309 and 289 vessels, respectively. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for CT-QFR in all lesions at the per-vessel level were 91% (with a 95% CI of 84%-96%), 92% (95% CI, 88%-95%), 83% (95% CI, 75%-90%), 96% (95% CI, 93%-98%), and 92% (95% CI, 88%-95%), with values for µQFR of 90% (95% CI, 81%-95%), 97% (95% CI, 93%-99%), 92% (95% CI, 84%-97%), 96% (95% CI, 92%-98%), and 94% (95% CI, 91%-97%), respectively. Among bifurcation, tandem, and moderate-to-severe calcified lesions, the diagnostic values of CT-QFR and µQFR showed great correlation and agreement with those of invasive fractional flow reserve, achieving an area under the receiver operating characteristic curve exceeding 0.9 for each complex lesion at the vessel level. Furthermore, the accuracies of CT-QFR and µQFR in the gray zone were 85% and 84%, respectively. CONCLUSIONS: Angiography-derived quantitative flow ratio (CT-QFR and µQFR) demonstrated remarkable diagnostic performance in complex coronary lesions, indicating its pivotal role in the management of patients with coronary artery disease.

Hemodynamic Effects of Tortuosity and Stenosis in Superficial Temporal Artery-Middle Cerebral Artery Bypass for Moyamoya Disease.

BACKGROUND: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass surgery has been widely adopted in treating moyamoya disease (MMD). Geometric variations including high tortuosity and stenosis exist in many cases, but the hemodynamic effects have not been comprehensively evaluated. We aim to evaluate the hemodynamic effects of bypass geometry variations based on patient-specific data. METHODS: In total, 17 patients with MMD who underwent STA-MCA bypass surgery with highly tortuous bypass geometry were included. For each patient, the original 3-dimensional structure of STA-MCA bypass was reconstructed from clinical imaging data. The bypass structure was virtually improved by removing the tortuosity and stenosis. Computational fluid dynamics simulation was performed on both bypass structures under identical patient-specific condition. The simulated hemodynamic parameters of the bypass and its distal branches were compared between the original and virtually improved bypass geometries in all cases using paired t-test or Wilcoxon signed-rank test. The changes of hemodynamic parameters were compared between the cases with and without mild-to-moderate stenosis (44.0-70.3% in diameter) in the bypass using t-test or Mann-Whitney U test. RESULTS: The virtual improvement of bypass geometry significantly increased the flow rate of the bypass and its distal branches (P < 0.05) and decreased the transcranial flow resistance (P < 0.05). The hemodynamic changes in cases with stenosis removal were significantly greater than those without stenosis (P < 0.05). CONCLUSIONS: High tortuosity and stenosis can significantly change the hemodynamics of STA-MCA bypass, and the optimization of bypass geometry deserves further consideration.

Phantom study of a self-shielded X-ray bone age assessment instrument against scattered radiation in children.

Hand-wrist radiography is the most common and accurate method for evaluating children's bone age. To reduce the scattered radiation of radiosensitive organs in bone age assessment, we designed a small X-ray instrument with radioprotection function by adding metal enclosure for X-ray shielding. We used a phantom operator to compare the scattered radiation doses received by sensitive organs under three different protection scenarios (proposed instrument, radiation personal protective equipment, no protection). The proposed instrument showed greater reduction in the mean dose of a single exposure compared with radiation personal protective equipment especially on the left side which was proximal to the X-ray machine (≥80.0% in eye and thyroid, ≥99.9% in breast and gonad). The proposed instrument provides a new pathway towards more convenient and efficient radioprotection.

Advancements in LAM-based diagnostic kit for tuberculosis detection: enhancing TB diagnosis in HIV-negative individuals.

Objective: The purpose of this study was to investigate the diagnostic value of urine lipoarabinomannan (LAM) detection based on chemiluminescence assay for pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in HIV-negative individuals. Methods: A total of 215 patients and 37 healthy individuals were included according to inclusion and exclusion criteria, including 173 cases of PTB and 42 cases of EPTB. Sputum smears, sputum culture, TB-RNA, GeneXpert, and urine LAM results were obtained from all patients before treatment. Using the composite reference standard as the reference, the diagnostic performance of these methods for PTB and EPTB was evaluated, and the diagnostic performance and cost-effectiveness of different combinations were analyzed. Results: In PTB, LAM exhibited the highest sensitivity (55.49%), followed by GeneXpert (44.51%). In EPTB, LAM also had the highest sensitivity (40.48%), followed by GeneXpert (33.33%). When combined with one method, LAM combined with GeneXpert showed the highest sensitivity for both PTB (68.79%) and EPTB (61.9%). When combined with two methods, culture, GeneXpert, and LAM showed the highest sensitivity for both PTB (73.99%) and EPTB (69.05%). In terms of cost-effectiveness analysis, the price of LAM was significantly lower than that of GeneXpert ($129.82 vs. $275.79 in PTB and 275.79 vs. 502.33 in EPTB). Among all combinations, the combination of LAM and sputum smear had the lowest cost, with prices of $124.94 for PTB and $263.72 for EPTB. Conclusion: Urine LAM detection based on chemiluminescence assay can be used as an adjunct diagnostic tool for PTB and EPTB in HIV-negative individuals. This facilitates expanding the current application of urine LAM from solely HIV-positive populations to the general population. LAM detection can overcome the limitations of obtaining clinical samples, and its ease of sample acquisition will be beneficial for its broader application in a larger scope. For economically better-off areas, we recommend using a combination of LAM + GeneXpert+culture for higher sensitivity; for economically disadvantaged areas, LAM + smear microscopy combination can provide a quick and accurate diagnosis of tuberculosis at a lower cost.

Baseline neurologic deficit and efficacy of remote ischemic conditioning after acute ischemic stroke: A post hoc analysis of RICAMIS.

RICAMIS (ClinicalTrials.gov Identifier: NCT03740971) trial has demonstrated efficacy of remote ischemic conditioning (RIC) in acute ischemic stroke, but whether baseline NIHSS score can affect outcomes in stroke remains unclear. We conducted a post hoc analysis of RICAMIS to investigate the issue. Patients included in RICAMIS were divided into three groups based on baseline NIHSS score. The primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0-1. Compared with patients receiving usual care, we investigated association of RIC effect with outcomes in each group and interaction between RIC effect and stroke severity. Among 1776 patients, 1255 were assigned into NIHSS score 6-8 group, 402 into NIHSS score 9-12 group, and 119 into NIHSS score 13-16 group. A higher proportion of primary outcome was found associated with RIC in NIHSS score 9-12 group (adjusted risk difference [RD], 14.6 â€‹%; 95 â€‹% CI, 5.0 â€‹%-24.2 â€‹%; P â€‹= â€‹0.003), but no significant association was found in NIHSS score 6-8 group (adjusted RD, 2.3 â€‹%; 95 â€‹% CI, -2.5 â€‹%-7.2 â€‹%; P â€‹= â€‹0.34), or in NIHSS score 13-16 group (adjusted RD, 9.7 â€‹%; 95 â€‹% CI, -7.5 â€‹%-26.9 â€‹%; P â€‹= â€‹0.27). There was a significant interaction between RIC effect and stroke severity when analysis was performed between NIHSS score 6-8 and 9-12 groups (P â€‹= â€‹0.04), but not between NIHSS score 9-12 and 13-16 groups (P â€‹= â€‹0.57). Current study firstly reported patients with NIHSS score 9-12 may get more benefit from RIC after stroke with respect to excellent functional outcome at 90 days.

Hepatocyte growth factor is protective in early stage but bone-destructive in late stage of experimental periodontitis.

BACKGROUND AND OBJECTIVE: Clinical studies found high levels of hepatocyte growth factor (HGF) expression in patients with periodontitis. Studies suggest that HGF plays an important role in periodontitis, is involved in inflammation, and modulates alveolar bone integrity in periodontitis. This study aims to investigate the effects and mechanisms of HGF in the progression of experimental periodontitis. METHODS: We used silk thread ligation to induce periodontitis in HGF-overexpressing transgenic (HGF-Tg) and wild-type C57BL/6J mice. The effects of HGF overexpression on alveolar bone destruction were assessed by microcomputed tomography imaging at baseline and on days 7, 14, 21, and 28. We analyzed the cytokines (IL-6 and TNF-α) and lymphocytes in periodontitis tissues by enzyme-linked immunosorbent assay and flow cytometry. The effects of HGF on alveolar bone destruction were further tested by quantifying the systemic bone metabolism markers CTXI and PINP and by RNA sequencing for the signaling pathways involved in bone destruction. Western blotting and immunohistochemistry were performed to further elucidate the involved signaling pathways. RESULTS: We found that experimental periodontitis increased HGF production in periodontitis tissues; however, the effects of HGF overexpression were inconsistent with disease progression. In the early stage of periodontitis, periodontal inflammation and alveolar bone destruction were significantly lower in HGF-Tg mice than in wild-type mice. In the late stage, HGF-Tg mice showed higher inflammatory responses and progressively aggravated bone destruction with continued stimulation of inflammation. We identified the IL-17/RANKL/TRAF6 pathway as a signaling pathway involved in the HGF effects on the progression of periodontitis. CONCLUSION: HGF plays divergent effects in the progression of experimental periodontitis and accelerates osteoclastic activity and bone destruction in the late stage of inflammation.

Tumor cell SPTBN1 inhibits M2 polarization of macrophages by suppressing CXCL1 expression.

Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, and the M2-type TAMs can promote tumor growth, invasion and angiogenesis, and suppress antitumor immune responses. It has been reported that spectrin beta, non-erythrocytic 1 (SPTBN1) may inhibit the infiltration of macrophages in Sptbn1+/-  mouse liver, but whether tumor SPTBN1 affects TAMs polarization remains unclear. This study investigated the effect and mechanism of tumor cell SPTBN1 on polarization and migration of TAMs in hepatoma and breast cancer. By analyzing tumor immune databases, we found a negative correlation between SPTBN1 and abundance of macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. By reverse transcription-quantitative real-time PCR assays and cell migration assays, the migration and M2 polarization of macrophages were enhanced by the culture medium from hepatocellular carcinoma cell line PLC/PRF/5, SNU449, and breast cancer cell line MDA-MB-231 with SPTBN1 suppression, which could be reversed by CXCL1 neutralizing antibody MAB275. Meanwhile, the ability of migration and colony formation of PLC/PRF/5, SNU449, and MDA-MB-231 cells were promoted when coculture with M2 macrophages. We also found that SPTBN1 regulated CXCL1 through p65 by cytoplasmic-nuclear protein isolation experiments and ChIP-qPCR. Our data suggest that tumor cell SPTBN1 inhibits migration and M2-type polarization of TAMs by reducing the expression and secretion of CXCL1 via inhibiting p65 nuclear localization.

BACH1 controls hepatic insulin signaling and glucose homeostasis in mice.

Hepatic insulin resistance is central to the metabolic syndrome. Here we investigate the role of BTB and CNC homology 1 (BACH1) in hepatic insulin signaling. BACH1 is elevated in the hepatocytes of individuals with obesity and patients with non-alcoholic fatty liver disease (NAFLD). Hepatocyte-specific Bach1 deletion in male mice on a high-fat diet (HFD) ameliorates hyperglycemia and insulin resistance, improves glucose homeostasis, and protects against steatosis, whereas hepatic overexpression of Bach1 in male mice leads to the opposite phenotype. BACH1 directly interacts with the protein-tyrosine phosphatase 1B (PTP1B) and the insulin receptor ß (IR-ß), and loss of BACH1 reduces the interaction between PTP1B and IR-ß upon insulin stimulation and enhances insulin signaling in hepatocytes. Inhibition of PTP1B significantly attenuates BACH1-mediated suppression of insulin signaling in HFD-fed male mice. Hepatic BACH1 knockdown ameliorates hyperglycemia and improves insulin sensitivity in diabetic male mice. These results demonstrate a critical function for hepatic BACH1 in the regulation of insulin signaling and glucose homeostasis.

Hydrogenation of levulinic acid to γ-valerolactone over hydrophobic Ru@HCP catalysts.

This study introduces an efficient strategy for promoting the synthesis of γ-valerolactone (GVL) via levulinic acid (LA) hydrogenation. A series of hyper-crosslinked porous polymer (HCP) supported Ru catalysts with different monomers were prepared. The wettabilities were controlled by the surface functional groups. The hydrophobic catalysts showed much higher activity than the hydrophilic ones in the hydrogenation of LA to GVL, highly possible due to the substrate enrichment. Further insight showed that the reaction proceeded through the 4-HVA route. These results illustrated the importance of surface wettability in bio-based molecule upgrading, which is beneficial for catalyst design.

BACH1 regulates the differentiation of vascular smooth muscle cells from human embryonic stem cells via CARM1-mediated methylation of H3R17.

The role of BACH1 in the process of vascular smooth muscle cell (VSMC) differentiation from human embryonic stem cells (hESCs) remains unknown. Here, we find that the loss of BACH1 in hESCs attenuates the expression of VSMC marker genes, whereas overexpression of BACH1 after mesoderm induction increases the expression of VSMC markers during in vitro hESC-VSMC differentiation. Mechanistically, BACH1 binds directly to coactivator-associated arginine methyltransferase 1 (CARM1) during in vitro hESC-VSMC differentiation, and this interaction is mediated by the BACH1 bZIP domain. BACH1 recruits CARM1 to VSMC marker gene promoters and promotes VSMC marker expression by increasing H3R17me2 modification, thus facilitating in vitro VSMC differentiation from hESCs after the mesoderm induction. The increased expression of VSMC marker genes by BACH1 overexpression is partially abolished by inhibition of CARM1 or the H3R17me2 inhibitor TBBD in hESC-derived cells. These findings highlight the critical role of BACH1 in hESC differentiation into VSMCs by CARM1-mediated methylation of H3R17.

α-SMA+ cancer-associated fibroblasts increased tumor enhancement ratio on contrast-enhanced multidetector-row computed tomography in stages I-III colon cancer.

BACKGROUND AND AIM: Our prior research revealed that the tumor enhancement ratio (TER) on triphasic abdominal contrast-enhanced MDCT (CE-MDCT) scans was a prognostic factor for patients with stages I-III colon cancer. Building upon this finding, the present study aims to investigate the proteomic changes in colon cancer patients with varying TER values. METHODS: TER was analyzed on preoperative triphasic CE-MDCT scans of 160 stages I-III colon cancer patients. The survival outcomes of those in the low-TER and high-TER groups were compared. Proteomic analysis on colon cancer tissues was performed by mass spectrometry (MS) and verified by immune-histological chemistry (IHC) assays. In vivo, mouse xenograft models were employed to test the function of target proteins identified through the MS. CE-MDCT scans were conducted on mice xenografts, and the TER values were compared. RESULTS: Patients in the high-TER group had a significantly worse prognosis than those in the low-TER group. Proteomic analysis of colon cancer tissues revealed 153 differentially expressed proteins between the two groups. A correlation between TER and the abundance of α-SMA protein in tumor tissue was observed. IHC assays further confirmed that α-SMA protein expression was significantly increased in high-TER colon cancer, predominantly in cancer-associated fibroblasts (CAFs) within the cancer stroma. Moreover, CAFs promoted the growth of CRC xenografts in vivo and increased TER. CONCLUSIONS: Our study identified the distinct protein changes in colon cancer with low and high TER for the first time. The presence of CAFs may promote the growth of colon cancer and contribute to an increased TER.

Dietary exposure to sulfamethazine alters fish intestinal homeostasis and promotes resistance gene transfer.

The present study was undertaken to explore the effects of sulfamethazine (SMZ) dietary exposure on the enrichment of the intestine microbial structure, and antibiotic resistance gene (ARGs) transmission in marine medaka, with respect to antibiotic dose, duration, and sex. In male fish, a dietary exposure of 10 µg/L SMZ led to a heightened SMZ enrichment in the intestine, whereas metabolite (N-SMZ) levels were elevated at a higher exposure concentration (100 µg/L). Conversely, female fish exhibited stable levels of accumulation and metabolic rates across the exposure period. The composition of intestinal microorganisms revealed that exposure duration exerted a greater impact on the abundance and diversity of gut microbes, and microbial responses to SMZ varied across exposure time points. The expansion of Bacteroidetes and Ruegeria likely stimulated SMZ metabolism and contributed to the more balanced level of SMZ and N-SMZ observed in females. In males, short-term SMZ stress resulted in a disruption of intestinal homeostasis, while the rise in the abundance of the Fusobacteria and Propionigeniuma suggested a potential enhancement in intestinal anti-inflammatory capacity over time. Overall, female medaka exhibited greater adaptability to SMZ, and males appear to experience prolonged effects due to SMZ. A total of 11 ARGs and 5 mobile genetic elements (MGEs) were identified. Ruegeria is the main carrier of two types of MGEs (IS1247, ISSm2-Xanthob), and may serve as an indicator of ARG transmission. Therefore, it is rational to consider some fish breeding areas in natural waters as potential "reservoirs" of antibiotic resistance. This research will provide a valuable reference for the transmission of drug resistance along the food chain.

Banxia Xiexin decoction: A review on phytochemical, pharmacological, clinical and pharmacokinetic investigations.

Banxia Xiexin decoction (BXD), a famous traditional Chinese prescription constituted by Pinelliae Rhizoma, Zingiberis Rhizoma, Scutellariae Radix, Coptidis Rhizoma, Ginseng Radix et Rhizoma, Jujubae Fructus and Glycyrrhizae Radix et Rhizoma Praeparata Cum Mell, has notable characteristics of acrid-opening, bitter down-bearing and sweet-tonification, interfering with tumors, gastrointestinal diseases, central nervous system diseases and much more. Based on the wide clinical applications, current investigations of BXD focused on several aspects: chemical analysis to explore the underlying substrates responsible for the therapeutic effects; basic studies on pharmacological actions of the whole prescription or of those representative ingredients to demonstrate the intriguing molecular targets for specific pathological processes; pharmacokinetic feature studies of single or all components of BXD to reveal the chemical basis and synergistic actions contributing to the pharmacological and clinically therapeutic effects. In this review, we summarized the main achievements of phytochemical, pharmacological, clinical and pharmacokinetic profiles of BXD and its herbal or pharmacologically active chemicals, as well as discussions of our understanding which further reveals the significance of BXD clinically.

[Retracted] Functional characterization of the nitrogen permease regulator­like­2 candidate tumor suppressor gene in colorectal cancer cell lines.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the microscopic images shown in Fig. 1C on p. 3489 and the invasion assay images shown in Fig. 5 on p. 3491 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes. Moreover, unexpected similarities were identified comparing between a pair of the flow cytometric assay data panels in Fig. 4 on p. 3490, considering that these data were intended to show the results from differently performed experiments. Owing to the fact that the contentious data in the above article had already been published, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 12: 3487­3493, 2015; DOI: 10.3892/mmr.2015.3881].

Comparison of concentration and extraction workflows for qPCR quantification of intI1 and vanA in untreated wastewater.

Quantitative polymerase chain reaction (qPCR) measurement of antibiotic resistance genes (ARGs) in untreated municipal wastewater may prove useful in combating the antimicrobial resistance crisis. However, harmonizing and optimizing qPCR-based workflows is essential to facilitate comparisons across studies, and includes achieving highly-effective ARG capture through efficient concentration and extraction procedures. In the current study, combinations of sample volume, membrane types and DNA extraction kits within filtration and centrifugation-based workflows were used to quantify 16S ribosomal RNA (16S rRNA), class 1 integron-integrase gene (intI1) and an ARG encoding resistance to vancomycin (vanA) in untreated wastewater sampled from three wastewater treatment plants (WWTPs). Highly abundant 16S rRNA and intI1 were detected in 100 % of samples from all three WWTPs using both 2 and 20 mL sample volumes, while lower prevalence vanA was only detected when using the 20 mL volume. When filtering 2 mL of wastewater, workflows with 0.20-/0.40-µm polycarbonate (PC) membranes generally yielded greater concentrations of the three targets than workflows with 0.22-/0.45-µm mixed cellulose ester (MCE) membranes. The improved performance was diminished when the sample volume was increased to 20 mL. Consistently greater concentrations of 16S rRNA, intI1 and vanA were yielded by filtration-based workflows using PC membranes combined with a DNeasy PowerWater (DPW) Kit, regardless of the sample volume used, and centrifugation-based workflows with DNeasy Blood & Tissue Kit for 2-mL wastewater extractions. Within the filtration-based workflows, the DPW kit yielded more detection and quantifiable results for less abundant vanA than the DNeasy PowerSoil Pro Kit and FastDNA™ SPIN Kit for Soil. These findings indicate that the performance of qPCR-based workflows for surveillance of ARGs in wastewater varies across targets, sample volumes, concentration methods and extraction kits. Workflows must be carefully considered and validated considering the target ARGs to be monitored.

MRI-based risk stratification for recurrent ischemic stroke in embolic stroke of undetermined source.

OBJECTIVE: Leukoaraiosis and other brain MRI-assessed parameters were shown to be associated with recurrent stroke in this population. We aimed to develop an MRI-based predictive tool for risk stratification of ESUS patients. METHODS: We retrospectively assessed consecutive patients who were diagnosed with ESUS and underwent brain MRI and performed a multivariable analysis with the outcome of recurrent stroke/TIA. Based on the coefficient of each covariate, we generated an integer-based point scoring system. The discrimination and calibration of the score were assessed using the area under the receiver operator characteristic curve, net reclassification improvement, integrated discrimination improvement, calibration curve, and decision curve analysis. Also, we compared the new score with a previously published score (ALM score). RESULTS: Among 176 patients followed for an overall period of 902.3 patient-years (median of 74 months), there were 39 recurrent ischemic stroke/TIAs (4.32 per 100 patient-years). Fazekas score (HR: 1.26, 95% CI: 1.03-1.54), enlarged perivascular space (EPVS) (HR: 2.76, 95% CI: 1.12-6.17), NIHSS at admission (HR: 1.11, 95% CI: 1.02-1.18), and infarct subtypes (HR: 2.88, 95% CI: 1.34-6.17) were associated with recurrent stroke/TIA. Accordingly, a score (FENS score) was developed with AUC-ROC values of 0.863, 0.788, and 0.858 for 1, 3, and 5 years, respectively. These were significantly better than the AUC-ROC of ALM score (0.635, 0.695, and 0.705, respectively). The FENS score exhibited better calibration and discrimination ability than the ALM score (Hosmer-Lemeshow test χ2 : 4.402, p = 0.819). CONCLUSION: The MRI-based FENS score can provide excellent predictive performance for recurrent stroke/TIA and may assist in risk stratification of ESUS patients.