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ABSTRACTThis study aimed to investigate the application of ultrasound attenuation imaging (ATI) and shear wave elastography (SWE) in the examination of patients with metabolism-related fatty liver disease (MAFLD). A total of 210 patients were retrospectively selected and divided into MAFLD group (n=84) and no MAFLD group (n=126). ROC curve was used to analyze the diagnostic efficacy of ATI value and SWE value for MAFLD. The MAFLD groups were divided into mild group (n=39), moderate group (n=28) and severe group (n=17). Spearman correlation was used to analyze the relationship between ATI values, SWE values and the severity of MAFLD. Waist circumference, BMI, ALT, AST, TG, CHOL, ATI and SWE in MAFLD group were higher than those in non-MAFLD group (P<0.05). ROC analysis showed that the AUC of ATI value in the diagnosis of MAFLD was 0.837 and the sensitivity, specificity and cutoff values were 83.46%, 70.35% and 0.63 dB/cm/MHZ. Waist circumference and BMI were significantly lower in the mild MAFLD group than in the moderate MAFLD group (P<0.05) and ALT, AST, TG, CHOL, ATI and SWE levels gradually increased with the severity of MAFLD (P<0.05). Correlation analysis showed that ATI was positively correlated with MAFLD severity (r=0.553, P<0.001, 95% CI=0.384~0.686) and SWE was significantly positively correlated with MAFLD severity (r=0.606, P<0.001, 95% CI=0.450~0.726). Both ATI and SWE are effective in the diagnosis and evaluation of MAFLD, but ATI is more effective in the diagnosis and SWE.

Antimony (Sb) isotopic fractionation is frequently used as a proxy for biogeochemical processes in nature. However, to date, little is known about Sb isotope fractionation in biologically driven reactions. In this study, Pseudomonassp. J1 was selected for Sb isotope fractionation experiments with varying initial Sb concentration gradients (50–200 μM) at pH 7.2 and 30 °C. Compared to the initial Sb(III) reservoir (δ123Sb = 0.03 ± 0.01 ∼ 0.06 ± 0.01‰), lighter isotopes were preferentially oxidized to Sb(V). Relatively constant isotope enrichment factors (ε) of −0.62 ± 0.06 and −0.58 ± 0.02‰ were observed for the initial Sb concentrations ranging between 50 and 200 μM during the first 22 days. Therefore, the Sb concentration has a limited influence on Sb isotope fractionation during Sb(III) oxidation that can be described by a kinetically dominated Rayleigh fractionation model. Due to the decrease in the Sb-oxidation rate by Pseudomonassp. J1, observed for the initial Sb concentration of 200 μM, Sb isotope fractionation shifted toward isotopic equilibrium after 22 days, with slightly heavy Sb(V) after 68 days. These findings provide the prospect of using Sb isotopes as an environmental tracer in the Sb biogeochemical cycle.

To address the challenges associated with initial point selection and to enhance the speed of analysis in ellipsometry data interpretation, this study introduces a novel algorithm based on whale optimisation. The algorithm is designed to accurately determine samples' thickness and refractive index across transparent wavelength ranges. Comparative analysis demonstrates that the Psi and Delta spectra generated by the proposed algorithm align more closely with those obtained through the traditional transfer matrix method (TMM), underscoring the algorithm's improved accuracy. Furthermore, the algorithm's efficacy is validated by the excellent agreement between the properties of the established sample model (thickness and refractive index) and those acquired by transfer matrix data. This validation confirms the utility of the proposed algorithm in fitting ellipsometry data, establishing it as a robust tool for extracting essential fitting parameters of samples with enhanced precision and efficiency.

Multi-dimensional performance evaluation is crucial for blockchain systems as it enables appropriate blockchain choosing for a given scenario and helps to pinpoint the bottleneck module of a blockchain system to optimize its performance. However, the existing evaluation frameworks for blockchain suffer from low system generality, inefficient workload execution, and incomprehensible evaluation metrics. In order to overcome their limitations, we design and implement the Generalized and Fine-grained Blockchain Evaluation (GFBE) framework. Specifically, we abstract 3 types of Universal Evaluation Interface (UEI) via the dynamic proxying approach to enable generalized evaluation of heterogeneous blockchain systems. Through the design of Lua-based workloads plugin with high flexibility and reusability, GFBE improves the efficiency of workload execution. To achieve comprehensive measurement, we define 15 key performance metrics across hierarchical layers of blockchain architecture. We also implement and deploy GFBE on 16 machines each with 8 CPUs and 16GB RAM, and evaluate three open-source blockchain systems namely Ethereum, ChainMaker, and Haihe smart chain. The experimental results demonstrate that GFBE efficiently and accurately measure 15 key performance metrics such as Contract Execution Efficiency at the contract layer, Consensus Agreement Time Ratio at the consensus layer, and State Query Time at the data layer. Compared with state-of-the-art frameworks such as BLOCKBENCH, Log-based, and Caliper, GFBE distinguishes itself as the only framework that encompasses the appealing features of universal interface, reusable workload, and all-layer metrics.

Recent decades have seen the remarkable development of China in medical accessibility and quality index, and the application of a number of new advanced cardiovascular technologies benefits more patients. However, according to the Annual Report on Cardiovascular Health and Diseases in China published in this article, which was organized and summarized by National Center for Cardiovascular Diseases, there is still a huge population living with risk factors of cardiovascular diseases (CVD), and the morbidity and mortality of CVD are increasing. It is estimated that there are around 330 million patients suffering from CVD currently, including 245 million of hypertension, 13 million of stroke, 45.3 million of peripheral artery disease, 11.39 million of coronary heart disease (CHD), 8.9 million of heart failure, 5 million of pulmonary heart disease, 4.87 million of atrial fibrillation, 2.5 million of rheumatic heart disease, and 2 million of congenital heart disease. Tobacco use, diet and nutrition factors, physical activity, overweight and obesity, and psychological factors are what affect cardiovascular health, while hypertension, dyslipidemia, diabetes, chronic kidney disease, metabolic syndrome, and air pollution are the risk factors for CVD. In this article, in addition to risk factors for CVD, we also report the epidemiological trends of CVD, including CHD, cerebrovascular disease, arrhythmias, valvular heart disease, congenital heart disease, cardiomyopathy, heart failure, pulmonary vascular disease and venous thromboembolism, and aortic and peripheral artery diseases, as well as the basic research and medical device development in CVD. In a word, China has entered a new stage of transforming from high-speed development focusing on scale growth to high-quality development emphasizing on strategic and key technological development to curb the trend of increasing incidence and mortality of CVD.

Emerging evidence shows that dietary oligosaccharides are important prebiotics that can improve intestinal flora, while dietary polyphenols can act directly on intestinal cells. However, information about their synergistic effects on gut health is still limited. In this study, alginate oligosaccharide (AOS) and cyanidin-3-O-glucoside (C3G) were selected as a common marine plant oligosaccharide and terrestrial plant polyphenol, respectively, to study their effects on intestinal health. The results show that, in comparison to their individual applications, the combination of AOS and C3G (mass ratio, 3:1) displayed a stronger ability to up-regulate the expression of tight junction proteins, while enhanced intestinal epithelial barrier was also observed and levels of mucin-2 and β-defensins were simultaneously increased in the intestinal mucus. Interestingly, the secretion of immunoglobulin A and immune-related cytokines were approximately doubled by the AOS + C3G mixture. In addition, the AOS + C3G mixture was found to be more conducive to the positive transformation of intestinal flora, which stimulated the growth of beneficial bacteria Akkermansia, Lachnospiraceaeand Feacalibaculumwhile inhibiting the growth of harmful bacteria Helicobacterand Turicibacter. The data generated herein thus suggests that dietary oligosaccharides and dietary polyphenols may be more beneficial to intestinal health when applied in combination than their individual effects alone.

Introduction: Lupus nephritis (LN) treatment aims to control and prevent flares and irreversible kidney damage. Around 30% of patients are unresponsive to treatment; however, real-world LN treatment patterns have not been reported. Objectives of this retrospective cohort study (GSK 209758) were to quantify the time to switching/re-initiating induction therapy in patients with LN initiating immunosuppressant therapy and conversion from induction to maintenance immunosuppressant therapy, and to assess corticosteroid use. Methods: Patients with LN initiating induction or maintenance immunosuppressant therapy were identified using claims data. Patients were followed up from the index date (immunosuppressant initiation date) until treatment discontinuation, death, disenrollment, administrative censoring, or the end of follow-up period. The cumulative incidence of switching/re-initiating induction therapy and conversion to maintenance therapy was estimated using outpatient pharmacy claims and procedure codes. Corticosteroid use was estimated using pharmacy claims; a mean daily dose of ≥ 7.5 mg/day was considered high. Results: In total, 5000 patients with LN contributed 5516 treatment episodes (induction cohort, N= 372; maintenance cohort, N= 5144). In the induction cohort, the cumulative incidence (95% confidence interval) of switching between induction therapies was 24.6% (20.1–30.0) at 12 months, while 59.6% (52.4–66.1) of patients converted to maintenance therapy at 12 months. In the maintenance cohort, 21.2% (19.9–22.5) re-initiated induction therapy at 12 months. Oral corticosteroid use decreased during the follow-up in both cohorts, but 21.5% of patients remained on a high dose at 12 months in the induction cohort, while 15.8% in the maintenance cohort were taking a high dose at 24 months. Conclusions: Around a quarter of patients with LN initiating immunosuppressant therapy switched within 12 months, while a fifth re-initiated induction therapy within 12 months. Use of high corticosteroid doses were observed during 24 months of follow-up. These data suggest that many patients do not respond to existing standard LN therapies.

Although Convolutional Neural Networks (CNNs) have achieved large successes on image data, the attributes of point cloud data, such as its irregular format and sparse 3D distribution, prevent CNNs from being applied to point cloud data directly. Although considerable works, e.g., Pointnet-like methods, Transformer, and graph methods, have been adopted to process point clouds, these works can not consume spatial information directly like CNNs, leading to the loss of spatial information. Our Continuous Volumetric Convolution Network (CVCN), featuring a novel self-learning continuous convolution kernel, is proposed to address this problem. The continuous convolution kernel omits the manually defined kernel function and the manually set positions of kernel points, which brings convenience and flexibility. Moreover, CVCN hybridizes continuous convolutions with traditional CNNs to eliminate the time-consuming Farthest Point Sampling algorithm. Compared with the state-of-the-art works, competitive results have been achieved on point cloud classification and segmentation tasks.

Background: Primary thyroid lymphoma (PTL) is a rare malignant disorder, and ultrasound plays an important role in PTL diagnosis and follow-up surveillance. Prediction of refractory/relapse events in PTL patients is an essential issue, yet no ultrasonic PTL features have been discovered to be related to refractory/local relapse events. Methods: From January 2008 to September 2022, newly diagnosed PTL patients in our center who underwent standard first-line treatment and received an ultrasound examination before treatment were enrolled. Data regarding patients’ clinical and sonographic features, as well as their therapeutic responses were collected. Subjects with an ideal prognosis were compared to those with refractory/relapse events. Results: In total, 37 PTL patients were analyzed, including 26 with diffuse large B-cell lymphoma, 2 with follicular lymphoma and 9 with mucosa-associated lymphoid tissue lymphoma. During the median follow-up of 25 months, 30 patients obtained a complete response, 4 were refractory patients, and 3 experienced local relapse. No significant difference was detected in the baseline clinical characteristics between patients with an ideal prognosis and those with refractory/local relapse events. In terms of sonographic features, however, an event-free survival (EFS) curve comparison revealed that patients with bilobar enlargement (defined as an anterior-posterior diameter > 2.5 cm on both sides of thyroid lobes) had a poorer EFS than those without (P&lt; 0.0001), and patients with diffuse type had a poorer EFS than those with mixed/nodular types (P= 0.043). No significant difference was observed in EFS between patients with or without signs of suspicious cervical lymph node metastasis, rich blood signal distribution or symptoms of trachea compression. Conclusions: PTL patients with an anterior-posterior diameter > 2.5 cm for both thyroid lobes or PTL patients of the diffuse ultrasound type could be prone to refractory/local relapse events.

In this paper, we will give a sufficient condition for the self-amalgamation of a handlebody to be strongly irreducible.

The goal of this study was to investigate the clinical characteristics, prognostic variables, and survival of patients with primary mediastinal diffuse large B cell lymphoma (PMBCL) in the rituximab era. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PMBCL patients diagnosed between 2000 and 2019. The Kaplan–Meier (K-M) technique and log-rank test were used to assess overall survival (OS) and disease-specific survival (DSS). The independent prognostic variables for OS and DSS were identified using univariate and multivariate Cox regression analysis. Nomograms were created to predict survival prospects according to identified prognostic indicators. Totally, 841 patients were enrolled with PMBCL. One-year, 5-year, and 10-year OS rates were 93.99%, 85.04%, and 81.76%, and the corresponding DSS rates were 95.27%, 87.37%, and 85.98%. The results of multivariate Cox regression analysis demonstrated that age, years of diagnosis, Ann arbor staging, and chemotherapy were independent prognostic factors for survival. Nomograms designed exclusively for PMBCL were created to forecast the likelihood of 1-year, 5-year, and 10-year OS and DSS, respectively. The Harrell concordance index (C-index) for the nomograms predictions of OS and DSS were 0.704 and 0.733, respectively, which showed the established model harboring powerful and accurate performance. The present study revealed that incidence of PMBCL has been consistently rising over the last 20 years. Simultaneously, survival rates have improved tremendously. Rituximab based immunochemotherapy has emerged as an effective treatment option, leading to enhanced OS and DSS outcomes. Furthermore, the nomograms specifically developed for PMBCL have demonstrated robustness and accuracy in forecasting OS and DSS rates at 1, 5, and 10 years. These predictive tools can be valuable for clinicians in accurately estimating prognosis and establishing personalized treatment plans and follow-up protocols.

Background: The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. Based on ultrasound features, many MTC cases without suspicious characteristics are not categorized as high risk for malignancy. This study was designed to comprehensively investigate the ultrasonic features of MTC on ultrasound and help identify thyroid nodules with a high risk of MTC. Methods: Between 2017 and 2023, we retrospectively reviewed 116 consecutive thyroid nodules with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as “ultrasound-high suspicious” (h-MTC) and “ultrasound-low suspicious” (l-MTC). Using the same database, a tumour size- and risk evaluation-matched control group comprising 62 lesions was randomly selected to compare the vascularity features of l-MTC disease. Results: We identified 85 h-MTC nodules (73.3%) and 31 l-MTC nodules (26.7%). For patients with l-MTC disease, 22/31 (71.0%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity in the l-MTC group than in the benign nodule group (23/31, 74.2% vs. 5/59, 4.8%, P &lt; 0.001). We also showed that more CHAMMAS IV patterns (central blood flow greater than perinodular flow) (87.1% vs. 32.3%, P &lt; 0.001)) and CHEN IV patterns (penetrating vascularity) (100% vs. 25.8%, P &lt; 0.001) were found in l-MTC than benign nodules. Conclusions: Vascularity features can help differentiate l-MTC from benign nodules; moreover, we report a novel sonographic vascularity pattern of l-MTC disease, penetrating branching vascularity. The utilization of vascularity features will help to identify MTC among nodules with low-intermediate suspicion by ultrasound risk classification to ensure appropriate clinical management.

In this work, an alkaline phosphatase (ALP) biosensor was established based on G-quadruplex/N-methylmesoporphyrin IX (G4/NMM) and p-nitrophenol (PNP). Because the absorption of PNP was close to the excitation wavelength of G4/ NMM, PNP could reduce the fluorescence of G4/NMM. Meanwhile, PNP was the hydrolysis product of p-nitrophenylphosphate (PNPP) by ALP. Therefore, ALP could be detected. This ALP biosensor had a linear analytical range from 2.5 to 25 U/L a the detection limit of 0.81 U/L. Moreover, it showed a satisfactory selectivity and recovery rates.

Traditional methods of seed viability evaluation based on germination or detecting physiological indicators have several disadvantages, such as time consumption, seed destruction, and skill requirements et al. In this study, a nondestructive method based on surface desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI–MS) was developed to evaluate radish [Raphanus sativus(L.) Domin] seed viability by detecting the sinapine that leakage from the interior of the seed to the coat. The signal intensity of the detected sinapine in seed coat by DAPCI–MS was significantly negatively correlated with the seed viability. One seed could be analyzed in an average of 4.4 s. We establish a new method to test radish seed viability based on DAPCI‐MS. This is a highly sensitive and high‐throughput method for detection without sample pretreatment. In addition, this study also provides new insights into the evaluation of seed viability in other plants.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin’s lymphoma (HL) or non-Hodgkin’s lymphoma (NHL), and it is also used as first-line clinical consolidation option for some aggressive NHL subtypes. Conditioning regimen prior to ASCT is one of the essential factors related with clinical outcomes post transplant. The conditioning regimen of carmustine, etoposide, cytarabine, and melphalan (BEAM) traditionally is considered the standard of care for patients with lymphoma who are eligible for transplantation. Replacement of carmustine with bendamustine (BeEAM) was described as an alternative conditioning regimen in the autograft setting for patients with lymphoma. Several studies have reported inconsistent clinical outcomes comparing BeEAM and BEAM. Therefore, in the lack of well-designed prospective comparative studies, the comparison of BeEAM versus BEAM is based on retrospective trials. To compare the clinical outcomes between BeEAM and BEAM, we performed a meta-analysis of 10 studies which compared the outcomes between BeEAM and BEAM in patients autografted for lymphoma disease (HL or NHL). We searched article titles and compared transplantation with BeEAM versus BEAM in MEDLINE (PubMed), Cochrane library, and EMBASE database. Here, we report the results of nine main endpoints in our meta-analysis comparing BeEAM and BEAM, including neutrophil engraftment (NE), platelet engraftment (PE), overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse rate (RR), grade 3 mucositis, renal toxicity, and cardiotoxicity. We discovered that the BeEAM regimen was associated with a slightly better PFS [pooled odds ratio (OR) of 0.70, 95% confidence interval (CI), 0.52–0.94, P= 0.02], lower RR (0.49, 95% CI, 0.31–0.76, P= 0.002), higher mucositis (3.43, 95% CI, 2.29–5.16, P= 0.001), renal toxicity (4.49, 95% CI, 2.68–7.51, P= 0.001), and cardiotoxicity (1.88, 95% CI, 1.03–3.40, P= 0.03). We also discovered that the two groups had equivalent NE (pooled WMD –0.64, 95% CI, –1.46 to 0.18, P= 0.13), PE (pooled WMD –0.3, 95% CI, –1.68 to 2.28, P= 0.77), OS (0.73, 95% CI, 0.52–1.01, P= 0.07), and NRM (1.51, 95% CI, 0.76–2.98, P= 0.24). The results of this meta-analysis show that the BeEAM regimen is a viable alternative to BEAM. More prospective comparisons between BeEAM and BEAM are required.

Although radiotherapy is a general oncology treatment and is often synergistically applied with surgery and chemotherapy, it can cause side effects during and after treatment. Gold nanoparticles were studied as a potential material to enhance radiation to induce damage in cancer cells. However, few studies have been conducted to examine the effects of gold nanofilm on cell impairment under X-ray treatment. This paper describes a microfabrication-based single-cell array platform to evaluate DNA damage induced by enhanced X-ray radiation on gold nanofilm patches (GNFPs). Cancer cells were patterned on GNFPs of different diameters and thicknesses, where each cell was attached on one GNFP. The end-point DNA damage induced by X-ray was examined in situ at the single-cell level using a halo assay. The preliminary data demonstrated that the enhancement of DNA damage was significantly related to the area and thickness of the GNFP. This platform may be hopefully used to establish the mathematical relationships among DNA damage, X-ray dosage, and thickness and area of the GNFP, and further contribute to radiation dosage screening for personalized radiotherapy.

Objective: The objective of this study was to describe the capture-recapture method used by the Philadelphia Department of Public Health to enhance surveillance of perinatal hepatitis B virus (HBV), report on results and limitations of the process, and determine why some HBV-positive mother-infant pairs were not initially identified by Philadelphia’s Perinatal Hepatitis B Prevention Program (PHBPP).Methods: We performed capture-recapture retrospectively for births in 2008 and 2009 in Philadelphia and prospectively for births from 2010 to 2014 by independently matching annual birth certificate data to PHBPP and HBV surveillance data. We compared the number of HBV-positive mother-infant pairs identified each year to the point estimates and lower-limit estimates calculated by the Centers for Disease Control and Prevention for the Philadelphia PHBPP.Results: Of 156 605 pregnancy outcomes identified between 2008 and 2014, we found 1549 HBV-positive mother-infant pairs. Of 705 pairs that were initially determined, 358 (50.7%) were confirmed to be previously unidentified HBV-positive pairs. Reasons for failing to identify these mother-infant pairs prior to capture-recapture included internal administrative issues (n = 191, 53.4%), HBV testing and reporting issues (n = 92, 25.7%), and being lost to follow-up (n = 75, 20.9%). Each year that capture-recapture was used, the number of pairs identified by the Philadelphia PHBPP exceeded the Centers for Disease Control and Prevention’s lower-limit estimates for HBV-positive mother-infant pairs.Conclusions: Capture-recapture was useful for identifying HBV-positive pregnant women for Philadelphia’s PHBPP and for highlighting inadequacies in health department protocols and HBV testing during pregnancy. Other health departments with access to similar data sources and staff members with the necessary technical skills can adapt this method.

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Objective: Parathyroid carcinoma (PC) and atypical parathyroid tumor (APT) are rare parathyroid disorders carrying the risk of recurrence of varying degrees. This study aims to explore the value of 2D-shear wave elastography (SWE) in the discrimination of PC/APT among suspicious parathyroid lesions. Methods and materials: In this prospective study, patients with primary hyperparathyroidism and suspicious parathyroid lesions on ultrasonography (US) were recruited. All the lesions were assessed by SWE before surgery. The velocity (m/s), Young’s modulus (Kpa), and elastogram of SWE were compared between pathologically proven parathyroid carcinoma or atypical parathyroid tumor (Group1) and parathyroid adenoma (Group2). All the SWE parameters were displayed at the setting of 50 or 70 kPa. Correlations between SWE and the lesion size as well as biochemical parameters were analyzed. Results: 36 target lesions were enrolled for analysis. The mean shear wave velocity (SWV) between the two groups was 2.4 m/s vs 1.9 m/s, respectively, while the mean Young’s modulus was 11.1 kPa vs 18.2 kPa, respectively. The cut-off values are 2.35 m/s and 17.05 kPa correspondingly. The sensitivity and specificity of the selecting cut-off values were 0.56 vs 0.63 and 0.95 vs 1.0 (area under the curve [AUC]: 0.813 vs 0.852 [95% confidence interval (CI): 0.669–0.956 vs 0.720–0.983]; p&lt;  0.001, p&lt;  0.001; respectively). In contrast, the max SWV and Young’s modulus showed a better sensitivity of 0.75 and 0.81, respectively. The “colored lesion” and “stiff rim” patterns on the elastogram are more indicated in parathyroid carcinoma and atypical parathyroid tumor, whereas the negative elastogram prevails in parathyroid adenoma. The SWV and Young’s modulus of the parathyroid lesions were independent of the tumor size, but the max SWV and Young’s modulus slightly correlated with serum parathyroid hormone concentration (PTH) (r = 0.398, p= 0.016; r = 0.396, p= 0.017). Conclusions: 2D-shear wave elastography plays a useful role in the preoperative assessment of parathyroid lesions with suspicious malignancy. The mean SWV and Young’s modulus are advised as the favored diagnostic parameter with the best AUC and excellent specificities, while the max SWV and Young’s modulus are more sensitive to distinguish the PC and APT compared with other parameters.

In this paper, the gauge equivalence between the modified Landau–Lifshitz equation and the perturbed defocusing nonlinear Schrödinger equation is proved from the perspective of geometry of given curvature condition. By using the gauge equivalence and the soliton perturbation theory of defocusing nonlinear Schrödinger equation, the first-order approximate 1-soliton solution to the modified Landau–Lifshitz equation is given. [ABSTRACT FROM AUTHOR]

IMPORTANCE: Fluoroquinolones are the most commonly prescribed antibiotic class in the outpatient setting. Recent reports have implicated an association between oral fluoroquinolones and an increased risk of uveitis. OBJECTIVE: To determine the hazard of uveitis with oral fluoroquinolone use. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted using medical claims data from a large national US insurer (N = 4 387 651). Cohorts from ambulatory care centers across the United States were created including every new user of an oral fluoroquinolone or β-lactam antibiotic prescription with at least 24 months of data prior to the date of the prescription from January 1, 2000, to January 30, 2013. Exclusion criteria consisted of any previous diagnosis of uveitis or a uveitis-associated systemic illness. Participants were censored for a new diagnosis of a uveitis-associated systemic illness, the end of an observation period, use of the other class of antibiotic, or removal from the insurance plan. Data analysis was performed from January 2 through March 15, 2015. MAIN OUTCOMES AND MEASURES: The hazard of a uveitis diagnosis after a fluoroquinolone prescription compared with a β-lactam prescription using multivariate regression with Cox proportional hazards models. RESULTS: Of the 4 387 651 patients in the database, 843 854 individuals receiving a fluoroquinolone and 3 543 797 patients receiving a β-lactam were included in the analysis. After controlling for age, race, and sex using multivariate analysis, no hazard for developing uveitis at the 30-, 60-, or 90-day observation windows was seen (hazard ratio [HR] range, 0.96; 95% CI, 0.82-1.13; to 1.05; 95% CI, 0.95-1.16; P > .38 for all comparisons). The 365-day observation period showed a small increase in the HR for the fluoroquinolone cohort (1.11; 95% CI, 1.05-1.17; P &lt; .001). Moxifloxacin produced an increased hazard for uveitis at every time point (HR range, 1.47-1.75; 95% CI, 1.27-2.37; P &lt; .001 for all comparisons). Secondary analysis demonstrated a similar hazard at 365 days for a later diagnosis of a uveitis-associated systemic illness after fluoroquinolone use (HR range, 1.46-1.96; 95% CI, 1.42-2.07; P &lt; .001 for all comparisons). CONCLUSIONS AND RELEVANCE: These data do not support an association between oral fluoroquinolone use and uveitis. Instead, this study shows an association between oral fluoroquinolone use and the risk for uveitis-associated systemic illnesses, which is a possible source of bias that could explain the findings of previous studies.

Hemophilia A is an inherited X-linked recessive bleeding disorder caused by coagulant factor VIII (FVIII) deficiency. The conventional treatment involves the administration of recombinant human FVIII (rhFVIII) preparations. In this study, the mammary gland ‘bioreactor’ is designed to specifically and efficiently express a foreign protein hFVIII in the mammary glands of transgenic mice. We constructed a P1A3-hFVIIIBD vector directed by the mammary gland-specific P1A3 promoter, and transiently transfected HC11 cells and mouse mammary glands with P1A3-hFVIIIBD or CMV-hFVIIIBD vectors directed by a ubiquitous cytomegalovirus (CMV) promoter, respectively. We also generated P1A3-hFVIIIBD and CMV-hFVIIIBD transgenic mice by microinjection, respectively. Our data indicated that both vectors effectively expressed hFVIIIBD in HC11 cells at the transcription level, and hFVIIIBD protein was efficiently expressed in mouse milk after the injection of the hFVIIIBD vectors into mouse mammary glands during lactation. In both CMV-hFVIIIBD and P1A3-hFVIIIBD transgenic mice, hFVIIIBD proteins were efficiently expressed in the mammary glands at the mRNA and protein levels. No significant difference was observed in hFVIIIBD levels between the CMV-hFVIIIBD and P1A3-hFVIIIBD transgenic mice (P > 0.05). However, the activity of hFVIII in CMV-directed transgenic mice was slightly higher than that in P1A3-directed transgenic mice (P < 0.05). While hFVIIIBD was present in multiple organs in CMV-hFVIIIBD mice, P1A3-hFVIIIBD mice showed negligible hFVIIIBD expression in organs other than the mammary glands. This study demonstrated that the mammary gland-specific P1A3-hFVIIIBD vector was more suitable for the generation of hFVIIIBD mammary gland bioreactor.

IMPORTANCE: Current draft guidelines set forth by the US Food and Drug Administration for compounded or repackaged medications would greatly limit the availability and use of bevacizumab by ophthalmologists across the country. Little evidence beyond highly publicized case reports exists for or against the need for additional regulation of compounded bevacizumab. OBJECTIVE: To determine whether the distribution of bevacizumab through compounding pharmacies increases the risk for endophthalmitis compared with the distribution of single-use vials of ranibizumab from the manufacturer. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using medical claims data from ambulatory care centers across the United States that were submitted to a large, national US insurer. Cohorts were created using information on 530 382 intravitreal injections administered from January 1, 2005, through December 31, 2012. Any individual from this data set who received an intravitreal injection of bevacizumab or ranibizumab (n=383 810) and had at least 6 months of data before and 1 month after the injection was eligible. After exclusions (any previous diagnosis of endophthalmitis, multiple injected drugs given on the index day, or intraocular surgery within 15 days of the injection or between the injection and a diagnosis of endophthalmitis), our analysis involved 383 810 intravitreal injections given to 58 612 patients. Data collection and analysis occurred from February 16 through April 7, 2015. MAIN OUTCOMES AND MEASURES: The odds of developing endophthalmitis after an intravitreal injection of bevacizumab compared with ranibizumab. RESULTS: In total, 296 565 injections of bevacizumab were given to 51 116 patients and 87 245 injections of ranibizumab were given to 7496 patients. We found 71 cases of endophthalmitis (49 in the bevacizumab cohort and 22 in the ranibizumab cohort) for an endophthalmitis rate of 0.017% (95% CI, 0.012%-0.021%; 1 case per 6061 injections) for bevacizumab and 0.025% (95% CI, 0.015%-0.036%; 1 case per 3968 injections) for ranibizumab. After controlling for age, race, sex, injection-related diagnosis, and year of injection, we found no significant association with development of endophthalmitis after a bevacizumab injection compared with ranibizumab (odds ratio, 0.66 [95% CI, 0.39-1.09]; P = .11). CONCLUSIONS AND RELEVANCE: The results of this study suggest bevacizumab as currently used across the United States does not increase the risk for endophthalmitis; therefore, additional regulations on the use of repackaged bevacizumab may be unnecessary.

A challenge of X-ray radiation therapy is that high dose X-rays at therapeutic conditions damage normal cells. This paper describes the use of gold nanoparticle-loaded multilayer microdisks to enhance X-ray radiation therapy, where each microdisk contains over 105radiosensitizing nanoparticles. The microdisks are attached on cell membranes through electrostatic interaction. Upon X-ray irradiation, more photoelectrons and Auger electrons are generated in the vicinity of the nanoparticles, which cause water ionization and lead to the formation of free radicals that damage the DNA of adjacent cancer cells. By attaching a large amount of gold nanoparticles on cancer cells, the total X-ray dose required for DNA damage and cell killing can be reduced. Due to their controllable structure and composition, multilayer microdisks can be a viable choice for enhanced radiation therapy with nanoparticles.

We introduce a class of partially coherent temporal/spatial sources, optical coherence gratings/lattices that have a Gaussian intensity profile and statistically stationary/homogeneous, periodic temporal/spatial coherence properties. We show that temporal coherence gratings generate partially coherent pulses with periodic spectra, whereas spatial coherence lattices yield far-zone output in the form of periodic lattices of highly directional beams.

There is an urgent need to develop taggants that can be used to identify objects, prevent fraud, and deter counterfeiting with high reliability, high capacity, and minimal effort. This paper describes a new multilayer covert taggant based on phase change nanoparticles (metals and eutectic alloys). A panel of selected nanoparticles with different melting temperatures have been added in matrix materials together with fluorescent dye and printed on substrates to form micro-/macrofeatures that contain thermal, fluorescence signature, and structural components. The multilayer taggants can greatly enhance security level for many commercial and forensic applications by their extremely large labeling capacity, coding readiness, and covertness.

This article describes a low cost method of generating silicon nanowire arrays that have similar structure and light trapping ability as moth-eye for matrix-free laser desorption/ionization mass spectrometry analysis of small molecules without matrix peak interference. The nanowire array is produced by combining low cost nanosphere lithography and metal nanoparticle-assisted chemical etching of silicon. Owing to their excellent light trapping ability over broad spectral range, silicon nanowire arrays can absorb incoming laser light efficiently, and convert laser energy to heat, which allows efficient desorption/ionization of intact peptide/proteins without matrix. Compared to existing matrix-free substrate such as porous silicon substrates, the biomimic silicon nanowire arrays are better in terms of lower laser energy, structural tunability, and low spatial resistance.

Three-dimensional (3D) ordered assemblies of semiconductive micro/nanowires are made by match-stick assembly of fibrous building blocks (FBBs). A glass tube filled with powders of starting material is processed drawn into centimeter-long, micrometer-diameter FBBs with controlled diameter and spacing. By repeating a draw-cut-stack process, the diameter and spacing of filling material can be programmably reduced from millimeters to hundreds of nanometers. The FBBs are densely packed into 3D ordered structures such that wires in one layer are at defined angle (?) relative to those in the adjacent layers, where ? is between 0 and 180°. The electrical measurements at bundled wires and single wire level confirm semiconducting behavior of wires. By directly manipulating microscale FBBs, the method allows high yield production of 3D ordered micro/nanowires with controlled position and orientation, enabling the construction of a new class of micro/nanomaterials.

Abstract: Objective: To demonstrate the alterations of Protein Kinase Cɛ (PKCɛ) and components of its signaling complexes after treatment with fosinopril and carvedilol and analyze potential molecular mechanisms of the two drugs for cardiac hypertrophy and heart failure. Methods: Pressure-overload cardiac hypertrophy (POH) was developed in 8-week-old male Sprague Dawley rats by abdominal aortic banding. The rats were divided into three groups at the age of 20 weeks: POH without failure group, reversed POH with drugs group, and POH with failure group on high diet. Western Blot analysis, co-immunoprecipitation and proteomic analysis were performed in ventricular tissues of rat hearts. Results: Increased PKCɛ was found during POH. PKCɛ decreased during transition from POH to heart failure (HF). However, increased PKCɛ inclined to recover to normal levels after treatment with both drugs. There were differential proteins in PKCɛ complexes during the different stages of POH. The two significant PKCɛ-binding proteins, MAD1 and Lyn A, were only present in PKCɛ complex during reversing POH with drugs. Conclusion: Chronic administration of carvedilol and fosinopril could reverse the development of POH and delay the appearance of HF, partly by regulating PKCɛ level and its signaling complex. MAD1 and Lyn A may be important proteins participating in the reversing process.

Hemophagocytic lymphohistiocytosis (HLH) is a rare fatal clinical syndrome characterized by a hyperinflammatory condition caused by aberrantly activated macrophages and cytotoxic T cells, resulting in a cytokine storm and organ impairment. Lymphoma, especially B-cell lymphoma in Japan, is a common trigger of secondary HLH. In China, however, most cases of HLH secondary to lymphoma occur in patients with T-cell/natural killer-cell lymphoma or Hodgkin`s lymphoma; HLH is relatively uncommon in patients with B-cell non-Hodgkin’s lymphoma. We herein describe a man with diffuse large B-cell lymphoma (DLBCL) and secondary HLH who was successfully treated by R-CHOP-E chemotherapy. All symptoms resolved and laboratory indications of HLH normalized, and complete remission of the lymphoma was achieved. This rare case highlights not only the possibility of HLH secondary to DLBCL but also the importance of early initiation of R-CHOP-E chemotherapy.

Haploidentical hematopoietic stem cell transplantation (Haplo-SCT) and umbilical cord blood transplantation (UCBT) are two important alternatives when a matched sibling donor is unavailable. Several studies have reported inconsistent clinical outcomes comparing Haplo-SCT and UCBT. Therefore, it is necessary to synthesize the existing evidence regarding outcomes of stem cell transplantations comparing Haplo-SCT with UCBT. We searched article titles that compared transplantation with Haplo-SCT and UCBT in MEDLINE (PubMed), Cochrane library, and EMBASE database. To compare clinical outcomes between Haplo-SCT and UCBT, we performed a meta-analysis of 12 studies and reported the pooled odds ratios (ORs) of 6 end points including overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), relapse rate (RR), acute graft-versus-host disease (aGVHD), and chronic graft-versus-host disease (cGVHD). We found that Haplo-SCT was associated with a significantly superior OS (pooled OR of 0.74, 95% confidence interval [CI] 0.68 to 0.80) and PFS (0.77, 95% CI 0.72 to 0.83), as well as a lower NRM (0.72, 95% CI 0.64 to 0.80) and aGVHD (0.87, 95% CI 0.77 to 0.98) compared to the UCBT group. We also found a significantly increased risk of cGVHD in Haplo-SCT group (1.40, 95% CI 1.22 to 1.62). In terms of RR, Haplo-SCT was comparable to UCBT (0.91, 95% CI 0.79 to 1.05). Results of this meta-analysis demonstrate that Haplo-SCT results in better clinical outcomes compared to UCBT in terms of OS, PFS, TRM, and aGVHD, but is inferior to UCBT in terms of increased cGVHD risk. Further prospective comparisons between Haplo-SCT and UCBT are needed.

Li: CARsgen Therapeutics Co. Ltd: Employment, Equity Ownership. Xiao:CARsgen Therapeutics Co. Ltd: Employment. WANG:CARsgen Therapeutics Co. Ltd: Employment. Yuan:CARsgen Therapeutics Co. Ltd: Employment. Ma:CARsgen Therapeutics Co. Ltd: Employment.

Inflammatory mechanisms are important in stroke risk, and genetic variation in components of the inflammatory response has been implicated as risk factors for stroke. We tested the inflammatory gene polymorphisms and their association with ischemic stroke in Chinese Han population.

Whether imatinib mesylate (IM)-based combinatory regimens could be an option for overcoming limitations of IM in treating chronic myeloid leukemia (CML), e.g., resistance developed by leukemic cells, unsatisfactory efficacy on patients at accelerated and blastic phases, and potential cardiotoxity, warrants further investigation. Here we report that the proteasome inhibitors, Bortezomib (BOR) and PSI, significantly potentiate proliferation/growth inhibition and enhance apoptotic effects of IM on K562 cells, CD34+ cells from CML patients, and BCR-ABL-expressing murine hematopoietic progenitor cells. BOR and PSI potentiate IM-triggered activation of caspases and inactivation of BCR-ABL oncoprotein, while caspase inhibitor blocks the apoptotic effect and reverse BCR-ABL inactivation. BOR/IM and PSI/IM combinations also attenuate DNA binding activity of NFκB. Intriguingly, low dose BOR/IM combination yields potent effects on inhibition of tumor growth, induction of apoptosis in leukemic cells, and inactivation of BCR-ABL oncoprotein, and does not cause weight loss or cardiotoxicity in null mice injected with K562 cells as compared to animals treated with IM at high doses. These results suggest a clinical trial to test the efficacy of IM/BOR combination in treating CML.