A YOLO-based AI system for classifying calcifications on spot magnification mammograms.

OBJECTIVES: Use of an AI system based on deep learning to investigate whether the system can aid in distinguishing malignant from benign calcifications on spot magnification mammograms, thus potentially reducing unnecessary biopsies. METHODS: In this retrospective study, we included public and in-house datasets with annotations for the calcifications on both craniocaudal and mediolateral oblique vies, or both craniocaudal and mediolateral views of each case of mammograms. All the lesions had pathological results for correlation. Our system comprised an algorithm based on You Only Look Once (YOLO) named adaptive multiscale decision fusion module. The algorithm was pre-trained on a public dataset, Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM), then re-trained and tested on the in-house dataset of spot magnification mammograms. The performance of the system was investigated by receiver operating characteristic (ROC) analysis. RESULTS: We included 1872 images from 753 calcification cases (414 benign and 339 malignant) from CBIS-DDSM. From the in-house dataset, 636 cases (432 benign and 204 malignant) with 1269 spot magnification mammograms were included, with all lesions being recommended for biopsy by radiologists. The area under the ROC curve for our system on the in-house testing dataset was 0.888 (95% CI 0.868-0.908), with a sensitivity of 88.4% (95% CI 86.9-8.99%), specificity of 80.8% (95% CI 77.6-84%), and an accuracy of 84.6% (95% CI 81.8-87.4%) at the optimal cutoff value. Using the system with two views of spot magnification mammograms, 80.8% benign biopsies could be avoided. CONCLUSION: The AI system showed good accuracy for classification of calcifications on spot magnification mammograms which were all categorized as suspicious by radiologists, thereby potentially reducing unnecessary biopsies.

Creating a Medical Imaging Workflow Based on FHIR, DICOMweb, and SVG.

This paper proposes a web-based workflow scheme for the organization of medical images using FHIR and DICOM servers equipped with standard RESTful APIs. In our integrated workflow, the client systems (including order placer, scheduler, imaging modality, viewer, and report creator) use standard FHIR and DICOMweb APIs. The proposed scheme also facilitates the creation of reports formatted as standard FHIR resources. This paper leverages W3C Scalable Vector Graphics (SVG) to record the image graphic annotations, and encapsulates the SVG image annotation in FHIR observation. FHIR DiagnosticReports and Observations are used to encapsulate reports, findings, and annotations, thereby facilitating the implementation and integration of the scheme within existing structures. The proposed scheme also provides the potential to make it possible to convert results of Computer Aided Detection/Diagnosis from medical images into FHIR DiagnosticReports and Observations to be stored on a FHIR server. The resulting web-based solution uses FHIR XML and/or JSON data to record and exchange information related to imaging workflow. It can also be used to store imaging reports, findings, and annotations linked to the images using the DICOM WADO-RS protocol. As a result, it is possible to integrate all information that is created in medical imaging workflow. Finally, the proposed scheme is easily integrated with other FHIR systems.

Temperature-Resolved Cryo-EM Uncovers Structural Bases of Temperature-Dependent Enzyme Functions.

Protein functions are temperature-dependent, but protein structures are usually solved at a single (often low) temperature because of limitations on the conditions of crystal growth or protein vitrification. Here we demonstrate the feasibility of solving cryo-EM structures of proteins vitrified at high temperatures, solve 12 structures of an archaeal ketol-acid reductoisomerase (KARI) vitrified at 4-70 °C, and show that structures of both the Mg2+ form (KARI:2Mg2+) and its ternary complex (KARI:2Mg2+:NADH:inhibitor) are temperature-dependent in correlation with the temperature dependence of enzyme activity. Furthermore, structural analyses led to dissection of the induced-fit mechanism into ligand-induced and temperature-induced effects and to capture of temperature-resolved intermediates of the temperature-induced conformational change. The results also suggest that it is preferable to solve cryo-EM structures of protein complexes at functional temperatures. These studies should greatly expand the landscapes of protein structure-function relationships and enhance the mechanistic analysis of enzymatic functions.

Use of Cryo-EM To Uncover Structural Bases of pH Effect and Cofactor Bispecificity of Ketol-Acid Reductoisomerase.

While cryo-EM is revolutionizing structural biology, its impact on enzymology is yet to be fully demonstrated. The ketol-acid reductoisomerase (KARI) catalyzes conversion of (2 S)-acetolactate or (2 S)-aceto-2-hydroxybutyrate to 2,3-dihydroxy-3-alkylbutyrate. We found that KARI from archaea Sulfolobus solfataricus (Sso-KARI) is unusual in being a dodecamer, bispecific to NADH and NADPH, and losing activity above pH 7.8. While crystals were obtainable only at pH 8.5, cryo-EM structures were solved at pH 7.5 and 8.5 for Sso-KARI:2Mg2+. The results showed that the distances of the two catalytic Mg2+ ions are lengthened in both structures at pH 8.5. We next solved cryo-EM structures of two Sso-KARI complexes, with NADH+inhibitor and NADPH+inhibitor at pH 7.5, which indicate that the bispecificity can be attributed to a unique asparagine at the cofactor binding loop. Unexpectedly, Sso-KARI also differs from other KARI enzymes in lacking "induced-fit", reflecting structural rigidity. Thus, cryo-EM is powerful for structural and mechanistic enzymology.

Therapeutic Effects of Monoclonal Antibody against Dengue Virus NS1 in a STAT1 Knockout Mouse Model of Dengue Infection.

Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti-DENV NS1 Ab-mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein. Passive immunization of DENV-infected mice with polyclonal anti-DJ NS1 Abs reduced viral Ag expression at skin inoculation sites and shortened DENV-induced prolonged bleeding time. We also investigated the therapeutic effects of anti-NS1 mAb. One mAb designated 2E8 does not recognize the C-terminal region of DENV NS1 in which host-cross-reactive epitopes reside. Moreover, mAb 2E8 recognizes NS1 of all four DENV serotypes. We also found that mAb 2E8 caused complement-mediated lysis in DENV-infected cells. In mouse model studies, treatment with mAb 2E8 shortened DENV-induced prolonged bleeding time and reduced viral Ag expression in the skin. Importantly, mAb 2E8 provided therapeutic effects against all four serotypes of DENV. We further found that mAb administration to mice as late as 1 d prior to severe bleeding still reduced prolonged bleeding time and hemorrhage. Therefore, administration with a single dose of mAb 2E8 can protect mice against DENV infection and pathological effects, suggesting that NS1-specific mAb may be a therapeutic option against dengue disease.

Unenhanced multidetector computed tomography findings in acute central pulmonary embolism.

BACKGROUND: Computed tomography pulmonary angiography (CTPA) is the gold standard for the diagnosis of pulmonary embolism (PE). However, contrast is contraindicated in some patients. The purpose of this study was to determine the diagnostic accuracy of unenhanced multidetector CT (MDCT) for diagnosis of central PE using CTPA as the gold standard. METHODS: The records of patients with suspected PE seen between 2010 and 2013 were retrospectively reviewed. Inclusion criteria were an acute, central PE confirmed by CTPA and non-enhanced MDCT before contrast injection. Patients with a PE ruled out by CTPA served as a control group. MDCT findings studied were high-attenuation emboli in pulmonary artery (PA), main PA dilatation > 33.2 mm, and peripheral wedge-shaped consolidation. Receiver operating characteristic (ROC) analysis was used to determine the sensitivity and specificity of unenhanced MDCT to detect PE. Wells score of all patients were calculated using data extracted from medical records prior to imaging analysis. RESULTS: Thirty-two patients with a PE confirmed by CTPA and 32 with a PE ruled out by CTPA were included. Among the three main MDCT findings, high-attenuation emboli in the PA showed best diagnostic performance (Sensitivity 72.9%; Specificity 100%), followed by main PA dilatation > 33.2 mm (sensitivity 46.9%; specificity 90.6%), and peripheral wedge-shaped consolidation (sensitivity 43.8%; specificity 78.1%). Given any one or more positive findings on unenhanced MDCT, the sensitivity was 96.9% and specificity was 71.9% for a diagnosis of PE in patients. The area under the curve (AUC) of a composite measure of unenhanced MDCT findings (0.909) was significantly higher than that of the Wells score (0.688), indicating unenhanced MDCT was reliable for detecting PE than Wells score. CONCLUSIONS: Unenhanced MDCT is an alternative for the diagnosis of acute central PE when CTPA is not available.

Crystal Structure Analysis of the Repair of Iron Centers Protein YtfE and Its Interaction with NO.

Molecular mechanisms underlying the repair of nitrosylated [Fe-S] clusters by the microbial protein YtfE remain poorly understood. The X-ray crystal structure of YtfE, in combination with EPR, magnetic circular dichroism (MCD), UV, and (17) O-labeling electron spin echo envelope modulation measurements, show that each iron of the oxo-bridged Fe(II) -Fe(III) diiron core is coordinatively unsaturated with each iron bound to two bridging carboxylates and two terminal histidines in addition to an oxo-bridge. Structural analysis reveals that there are two solvent-accessible tunnels, both of which converge to the diiron center and are critical for capturing substrates. The reactivity of the reduced-form Fe(II) -Fe(II) YtfE toward nitric oxide demonstrates that the prerequisite for N2 O production requires the two iron sites to be nitrosylated simultaneously. Specifically, the nitrosylation of the two iron sites prior to their reductive coupling to produce N2 O is cooperative. This result suggests that, in addition to any repair of iron centers (RIC) activity, YtfE acts as an NO-trapping scavenger to promote the NO to N2 O transformation under low NO flux, which precedes nitrosative stress.

The association of infrared imaging findings of the breast with prognosis in breast cancer patients: an observational cohort study.

BACKGROUND: To evaluate whether infrared (IR) imaging findings are associated with prognosis in patients with invasive breast carcinomas. METHODS: This study was approved by the institutional review board of the research ethics committee of our hospital, and all participants gave written informed consent. From March 2005 to June 2007, we enrolled 143 patients with invasive breast cancer that underwent preoperative IR imaging. We used five IR signs to interpret breast IR imaging. Cox proportional hazards model was used to evaluate the effect of IR signs on long-term mortality. RESULTS: During a median follow-up of 2451 days (6.7 years), 31 patients died. Based on the Cox Proportional Hazards Model, IR1 sign (the temperature of cancer site minus that of the contralateral mirror imaging site) was positively associated with mortality in the univariate analysis (overall mortality hazard ratio [HR], 2.29; p = 0.03; disease-specific mortality HR, 2.57; p = 0.04) as well as the multivariate analysis after controlling for clinicopathological factors (overall mortality HR, 3.85; p = 0.01; disease-specific mortality HR, 3.91, p = 0.02). In patients with clinical stage I and II disease, IR1 was also positively associated with mortality (overall mortality HR, 3.76; p = 0.03; disease-specific mortality HR, 4.59; p = 0.03). Among patients with node-negative disease, IR1 and IR5 (asymmetrical thermographic pattern) were associated with mortality (p = 0.04 for both IR1 and IR5, chi-squared test). CONCLUSION: Breast IR findings are associated with mortality in patients with invasive breast carcinomas. The association remained in patients with node-negative disease. TRIAL REGISTRATION: NCT00166998 .

Vanderwaltozyma polyspora possesses two glycyl-tRNA synthetase genes: one constitutive and one inducible.

Aminoacyl-tRNA synthetases are housekeeping enzymes essential for protein synthesis. We herein present evidence that the yeast Vanderwaltozyma polyspora possesses two paralogous glycyl-tRNA synthetase (GlyRS) genes-GRS1 and GRS2. Paradoxically, GRS1 provided functions in both the cytoplasm and mitochondria, while GRS2 was essentially silent under normal growth conditions. Expression of GRS2 could be activated by stresses such as high pH or ethanol and most effectively by high temperature. The expressed GlyRS2 protein was exclusively found in the cytoplasm and more stable under heat-shock conditions (37°C) than under normal growth conditions (30°C) in vivo. In addition, GRS2 effectively rescued the cytoplasmic defect of a Saccharomyces cerevisiae GRS1 knockout strain when expressed from a constitutive promoter. Moreover, the purified GlyRS2 enzyme was fairly active at both 30°C and 37°C in glycylation of yeast tRNA in vitro. However, unexpectedly, the purified GlyRS2 enzyme was practically inactive at temperature above 40°C in vitro. Our study suggests that GRS2 is an inducible gene that acts under stress conditions where GlyRS1 may be insufficient, unavailable, or rendered inactive.

Optical properties associated with strain relaxations in thick InGaN epitaxial films.

Structural and optical properties of thick InGaN layers with strain and composition inhomogeneities are investigated. High resolution x-ray diffractions (XRD) and reciprocal space mapping (RSM) along an asymmetric axis reveal that the In composition inhomogeneity is accompanied by strain relaxations during the growth of thick InGaN layers. According to the structural analysis, the commonly observed double photoluminescence (PL) peaks have been confirmed to be associated with the strain relaxation in thick InGaN films. Temperature-dependent PL measurements further indicate that the relaxed phase in InGaN films exhibits better emission efficiency than the strained phase. Recombination dynamics reveal that the carrier localization effect is more pronounced in the relaxed phase due to the compositional pulling effect. The correlations between emission efficiency and localization effect in thick InGaN films are discussed.

Dual dimeric interactions in the nucleic acid-binding protein Sac10b lead to multiple bridging of double-stranded DNA.

Nucleoid-associated proteins play a crucial role in the compaction and regulation of genetic material across organisms. The Sac10b family, also known as Alba, comprises widely distributed and highly conserved nucleoid-associated proteins found in archaea. Sac10b is identified as the first 10 kDa DNA-binding protein in the thermoacidophile Sulfolobus acidocaldarius. Here, we present the crystal structures of two homologous proteins, Sac10b1 and Sac10b2, as well as the Sac10b1 mutant F59A, determined at a resolution of 1.4-2.0 Å. Electron microscopic images reveal the DNA-bridging capabilities of both Sac10b1 and Sac10b2, albeit to varying extents. Analyses of crystal packing and electron microscopic results suggest that Sac10b1 facilitates cooperative DNA binding, forming extensive bridged filaments via the conserved R58 and F59 residues at the dimer-dimer interface. Substitutions at R58 or F59 of Sac10b1 attenuate end-to-end association, resulting in non-cooperative DNA binding, and formation of small, bridged DNA segments in a way similar to Sac10b2. Analytical ultracentrifuge and circular dichroism confirm the presence of thermostable, acid-tolerant dimers in both Sac10b1 and Sac10b2. These findings attest to the functional role of Sac10b in organizing and stabilizing chromosomal DNA through distinct bridging interactions, particularly under extreme growth conditions.

Mapping RNA exit channel on transcribing RNA polymerase II by FRET analysis.

A simple genetic tag-based labeling method that permits specific attachment of a fluorescence probe near the C terminus of virtually any subunit of a protein complex is implemented. Its immediate application to yeast RNA polymerase II (pol II) enables us to test various hypotheses of RNA exit channel by using fluorescence resonance energy transfer (FRET) analysis. The donor dye is labeled on a site near subunit Rpb3 or Rpb4, and the acceptor dye is attached to the 5' end of RNA transcript in the pol II elongation complex. Both in-gel and single-molecule FRET analysis show that the growing RNA is leading toward Rpb4, not Rpb3, supporting the notion that RNA exits through the proposed channel 1. Distance constraints derived from our FRET results, in conjunction with triangulation, reveal the exit track of RNA transcript on core pol II by identifying amino acids in the vicinity of the 5' end of RNA and show that the extending RNA forms contacts with the Rpb7 subunit. The significance of RNA exit route in promoter escape and that in cotranscriptional mRNA processing is discussed.

Radiomics for the Prediction of Response to Antifibrotic Treatment in Patients with Idiopathic Pulmonary Fibrosis: A Pilot Study.

Antifibrotic therapy has changed the treatment paradigm for idiopathic pulmonary fibrosis (IPF); however, a subset of patients still experienced rapid disease progression despite treatment. This study aimed to determine whether CT-based radiomic features can predict therapeutic response to antifibrotic agents. In this retrospective study, 35 patients with IPF on antifibrotic treatment enrolled from two centers were divided into training (n = 26) and external validation (n = 9) sets. Clinical and pulmonary function data were collected. The patients were categorized into stable disease (SD) and progressive disease (PD) groups based on functional or radiologic criteria. From pretreatment non-enhanced high-resolution CT (HRCT) images, twenty-six radiomic features were extracted through whole-lung texture analysis, and six parenchymal patterns were quantified using dedicated imaging platforms. The predictive factors for PD were determined via univariate and multivariate logistic regression analyses. In the training set (SD/PD: 12/14), univariate analysis identified eight radiomic features and ground-glass opacity percentage (GGO%) as potential predicators of PD. However, multivariate analysis found that the single independent predictor was the sum entropy (accuracy, 80.77%; AUC, 0.75). The combined sum entropy-GGO% model improved the predictive performance in the training set (accuracy, 88.46%; AUC, 0.77). The overall accuracy of the combined model in the validation set (SD/PD: 7/2) was 66.67%. Our preliminary results demonstrated that radiomic features based on pretreatment HRCT could predict the response of patients with IPF to antifibrotic treatment.

Mineralocorticoid Receptor Antagonists Mitigate Mitral Regurgitation-Induced Myocardial Dysfunction.

Mitral regurgitation (MR), the disruption of the mitral valve, contributes to heart failure (HF). Under conditions of volume overload, excess mineralocorticoids promote cardiac fibrosis. The mineralocorticoid receptor antagonist spironolactone is a potassium-sparing diuretic and a guideline-recommended therapy for HF, but whether it can ameliorate degenerative MR remains unknown. Herein, we investigate the efficacy of spironolactone in improving cardiac remodeling in MR-induced HF compared with that of a loop diuretic, furosemide. Using a novel and mini-invasive technique, we established a rat model of MR. We treated the rats with spironolactone or furosemide for twelve weeks. The levels of cardiac fibrosis, apoptosis, and stress-associated proteins were then measured. In parallel, we compared the cardiac remodeling of 165 patients with degenerative MR receiving either spironolactone or furosemide. Echocardiography was performed at baseline and at six months. In MR rats treated with spironolactone, left ventricular function-especially when strained-and the pressure volume relationship significantly improved compared to those of rats treated with furosemide. Spironolactone treatment demonstrated significant attenuation of cardiac fibrosis and apoptosis in left ventricular tissue compared to furosemide. Further, spironolactone suppressed the expression of apoptosis-, NADPH oxidase 4 (NOX4)- and inducible nitric oxide synthase (iNOS)-associated proteins. Similarly, compared with MR patients receiving furosemide those prescribed spironolactone demonstrated a trend toward reduction in MR severity and showed improvement in left ventricular function. Collectively, MR-induced cardiovascular dysfunction, including fibrosis and apoptosis, was effectively attenuated by spironolactone treatment. Our findings suggest a potential therapeutic option for degenerative MR-induced HF.

Elastases from inflammatory and dendritic cells mediate ultrafine carbon black induced acute lung destruction in mice.

CONTEXT: Exposure to ultrafine particles (<100 nm in diameter) is postulated to cause chronic obstructive pulmonary disease (COPD). However, the mechanism remains to be elucidated. OBJECTIVE: We aimed to evaluate whether ultrafine particle exposure causes the infiltration of inflammatory and dendritic cells (DCs) with increased elastase activity, contributing to lung parenchymal destruction. MATERIALS AND METHODS: C57BL/6 male mice were intratracheally instilled with 300 µg ultrafine carbon black (ufCB; 14 nm in diameter), and sacrificed at 1, 3, 7 and 14 d post-exposure. Differential cell counts, elastase activities, and desmosine and hydroxyproline in bronchoalveolar (BAL) fluid were determined. Immunofluorescent staining and flow cytometry analysis determined the cell origin of macrophage metalloelastase (MMP-12). Anti-neutrophil antibody was applied to assess the contribution of elastase in ufCB induced lung destruction. RESULTS: ufCB exposure led to significant increases in neutrophils, mononuclear cells and total proteins in BAL fluid. Desmosine and hydroxyproline were significantly increased in the ufCB group. Elastase activities were found to be significantly elevated, with both neutrophil elastase and MMP-12 peaking at 3 d post-exposure. Flow cytometry analysis demonstrated that pulmonary infiltrations of MMP-12 positive DCs, including Langerhans cells-derived DCs, occurred at 3 d and 7 d, while macrophage infiltration was obvious starting at 1 d. Anti-neutrophil antibody significantly reduced neutrophil elastase activity and prevented the increases in BAL desmosine and hydroxyproline following ufCB exposure. CONCLUSION: For the first time we demonstrate the infiltration of Langerhans and myeloid dendritic cells, and show that elastase production contributes to pulmonary destruction following exposure to ultrafine particles.

Preparation of High-Temperature Sample Grids for Cryo-EM.

The sample grids for cryo-electron microscopy (cryo-EM) experiments are usually prepared at a temperature optimal for the storage of biological samples, mostly at 4 °C and occasionally at room temperature. Recently, we discovered that the protein structure solved at low temperature may not be functionally relevant, particularly for proteins from thermophilic archaea. A procedure was developed to prepare protein samples at higher temperatures (up to 70 °C) for cryo-EM analysis. We showed that the structures from samples prepared at higher temperatures are functionally relevant and temperature dependent. Here we describe a detailed protocol for preparing sample grids at high temperature, using 55 °C as an example. The experiment made use of a vitrification apparatus modified using an additional centrifuge tube, and samples were incubated at 55 °C. The detailed procedures were fine-tuned to minimize vapor condensation and obtain a thin layer of ice on the grid. Examples of successful and unsuccessful experiments are provided.

Myocardial Infarction and Azygos Vein Thrombosis After ChAdOx1 nCoV-19 Vaccination in a Hemodialysis Patient.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after vaccination of Oxford-AstraZeneca coronavirus disease 2019 (COVID-19) vaccine (AZD1222) or Janssen COVID-19 vaccine. It makes a rare complication of thrombosis at common and/or uncommon organs with thrombocytopenia after COVID-19 vaccination four to 28 days later and most patients were younger than 60 years of age. We reported the case of a 75-year-old female with end-stage renal disease who received regular hemodialysis. She received Oxford-AstraZeneca COVID-19 vaccination eight days ago and then she suffered from intermittent chest tightness and epigastric pain with tarry stool passage for two days. Severe thrombocytopenia with elevated D-dimer value was noted and computed tomography of the chest showed azygos vein thrombosis. Elevated cardiac enzyme with ST-T change in 12-lead electrocardiogram was also noted. For positive anti-platelet factor 4 antibodies, VITT with myocardial infarction and azygos vein thrombosis was diagnosed.

Dapagliflozin Improves Cardiac Hemodynamics and Mitigates Arrhythmogenesis in Mitral Regurgitation-Induced Myocardial Dysfunction.

Background Mitral regurgitation (MR) is a major contributor for heart failure (HF) and atrial fibrillation. Despite the advancement of MR surgeries, an effective medical therapy to mitigate MR progression is lacking. Sodium glucose cotransporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality but the mechanism is unclear. We hypothesized that dapagliflozin (DAPA), a sodium glucose cotransporter 2 inhibitor, can improve cardiac hemodynamics in MR-induced HF. Methods and Results Using a novel, mini-invasive technique, we established a MR model in rats, in which MR induced left heart dilatation and functional decline. Half of the rats were randomized to be administered with DAPA at 10 mg/kg per day for 6 weeks. After evaluation of electrocardiography and echocardiography, hemodynamic studies were performed, followed by postmortem tissue analyses. Results showed that DAPA partially rescued MR-induced impairment including partial restoration of left ventricular ejection fraction and end-systolic pressure volume relationship. Despite no significant changes in electrocardiography at rest, rats treated with DAPA exhibited lower inducibility and decreased duration of pacing-induced atrial fibrillation. DAPA also significantly attenuated cardiac fibrosis, cardiac expression of apoptosis, and endoplasmic reticulum stress-associated proteins. Conclusions DAPA was able to suppress cardiac fibrosis and endoplasmic reticulum stress and improve hemodynamics in an MR-induced HF rat model. The demonstrated DAPA effect on the heart and its association with key molecular contributors in eliciting its cardio-protective function, provides a plausible point of DAPA as a potential strategy for MR-induced HF.

Rapid Fabrication of Biocomposites by Encapsulating Enzymes into Zn-MOF-74 via a Mild Water-Based Approach.

A zinc-based metal organic framework, Zn-MOF-74, which has a unique one-dimensional (1D) channel and nanoscale aperture size, was rapidly obtained in 10 min using a de novo mild water-based system at room temperature, which is an example of green and sustainable chemistry. First, catalase (CAT) enzyme was encapsulated into Zn-MOF-74 (denoted as CAT@Zn-MOF-74), and comparative assays of biocatalysis, size-selective protection, and framework-confined effects were investigated. Electron microscopy and powder X-ray diffraction were used for characterization, while electrophoresis and confocal microscopy confirmed the immobilization of CAT molecules inside the single hexagonal MOF crystals at loading of ∼15 wt %. Furthermore, the CAT@Zn-MOF-74 hybrid was exposed to a denaturing reagent (urea) and proteolytic conditions (proteinase K) to evaluate its efficacy. The encapsulated CAT maintained its catalytic activity in the decomposition of hydrogen peroxide (H2O2), even when exposed to 0.05 M urea and proteinase K, yielding an apparent observed rate constant (kobs) of 6.0 × 10-2 and 6.6 × 10-2 s-1, respectively. In contrast, free CAT exhibited sharply decreased activity under these conditions. Additionally, the bioactivity of CAT@Zn-MOF-74 for H2O2 decomposition was over three times better than that of the biocomposites based on zeolitic imidazolate framework 90 (ZIF-90) owing to the nanometer-scaled apertures, 1D channel, and less confinement effects in Zn-MOF-74 crystallites. To demonstrate the general applicability of this strategy, another enzyme, α-chymotrypsin (CHT), was also encapsulated in Zn-MOF-74 (denoted as CHT@Zn-MOF-74) for action against a substrate larger than H2O2. In particular, CHT@Zn-MOF-74 demonstrated a biological function in the hydrolysis of l-phenylalanine p-nitroanilide (HPNA), the activity of ZIF-90-encapsulated CHT was undetectable due to aperture size limitations. Thus, we not only present a rapid eco-friendly approach for Zn-MOF-74 synthesis but also demonstrate the broader feasibility of enzyme encapsulation in MOFs, which may help to meet the increasing demand for their industrial applications.

Evaluation of the diagnostic performance of infrared imaging of the breast: a preliminary study.

BACKGROUND: The study was conducted to investigate the diagnostic performance of infrared (IR) imaging of the breast using an interpretive model derived from a scoring system. METHODS: The study was approved by the Institutional Review Board of our hospital. A total of 276 women (mean age = 50.8 years, SD 11.8) with suspicious findings on mammograms or ultrasound received IR imaging of the breast before excisional biopsy. The interpreting radiologists scored the lesions using a scoring system that combines five IR signs. The ROC (receiver operating characteristic) curve and AUC (area under the ROC curve) were analyzed by the univariate logistic regression model for each IR sign and an age-adjusted multivariate logistic regression model including 5 IR signs. The cut-off values and corresponding sensitivity, specificity, Youden's Index (Index = sensitivity+specificity-1), positive predictive value (PPV), negative predictive value (NPV) were estimated from the age-adjusted multivariate model. The most optimal cut-off value was determined by the one with highest Youden's Index. RESULTS: For the univariate model, the AUC of the ROC curve from five IR signs ranged from 0.557 to 0.701, and the AUC of the ROC from the age-adjusted multivariate model was 0.828. From the ROC derived from the multivariate model, the sensitivity of the most optimal cut-off value would be 72.4% with the corresponding specificity 76.6% (Youden's Index = 0.49), PPV 81.3% and NPV 66.4%. CONCLUSIONS: We established an interpretive age-adjusted multivariate model for IR imaging of the breast. The cut-off values and the corresponding sensitivity and specificity can be inferred from the model in a subpopulation for diagnostic purpose. TRIAL REGISTRATION: NCT00166998.