Trimodal Multiplexed Lateral Flow Test Strips Assisted with a Portable Microfluidic Centrifugation Device.

During the COVID-19 pandemic, the use of lateral flow assays (LFAs) expanded significantly, offering testing beyond traditional health care. Their appeal lies in the ease of use, affordability, and quick results. However, LFAs often have lower sensitivity and specificity compared with ELISA and PCR tests. Efforts to improve LFAs have increased detection times and complexity, limiting their use in large-scale point-of-care settings. To address this, we propose a novel approach using probes that generate multiple signals to enhance the sensitivity and selectivity. This concept also allows multiplexed LFAs to detect multiple analytes concurrently. We developed a trimodal probe that integrates fluorescence, color, and magnetism into a single nanohybrid. The strong plasmonic absorption and high fluorescence of Au nanoparticles and polymer dots enable qualitative and semiquantitative diagnosis, while the magnetic signal facilitates accurate quantitative measurements. As proof-of-concept targets, we selected CYFRA 21-1 and CA15-3, biomarkers for lung and breast cancer, respectively. This trimodal LFA demonstrated a remarkable detection limit of 0.26 ng/mL for CYFRA 21-1 and 2.8 U/mL for CA15-3. To the best of our knowledge, this is the first platform of a trimodal LFA with multiplexing ability. The platform's accuracy and reliability were validated using clinical serum samples, showing excellent consistency with electrochemiluminescence immunoassay results. This universal concept can be applied to other targets, paving the way for the next-generation LFAs.

Rational Design of Asymmetric Polymethines to Attain NIR(II) Bioimaging at >1100 nm.

Organic molecules having emission in the NIR(II) region are emergent and receiving enormous attention. Unfortunately, attaining accountable organic emission intensity around the NIR(II) region is hampered by the dominant internal conversion operated by the energy gap law, where the emission energy gap and the associated internal reorganization energy λint play key roles. Up to the current stage, the majority of the reported organic NIR(II) emitters belong to those polymethines terminated by two symmetric chromophores. Such a design has proved to have a small λint that greatly suppresses the internal conversion. However, the imposition of symmetric chromophores is stringent, limiting further development of organic NIR(II) dyes in diversity and versatility. Here, we propose a new concept where as far as the emissive state of the any asymmetric polymethines contains more or less equally transition density between two terminated chromophores, λint can be as small as that of the symmetric polymethines. To prove the concept, we synthesize a series of new polymethines terminated by xanthen-9-yl-benzoic acid and 2,4-diphenylthiopyrylium derivatives, yielding AJBF1112 and AEBF1119 that reveal emission peak wavelength at 1112 and 1119 nm, respectively. The quantum yield is higher than all synthesized symmetric polymethines of 2,4-diphenylthiopyrylium derivatives (SC1162, 1182, 1185, and 1230) in this study. λint were calculated to be as small as 6.2 and 7.3 kcal/mol for AJBF1112 and AEBF1119, respectively, proving the concept. AEBF1119 was further prepared as a polymer dot to demonstrate its in vitro specific cellular imaging and in vivo tumor/bone targeting in the NIR(II) region.

Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data.

BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

[Reducing Abnormal Culture Rates of Digestive Endoscopy in a Health Management Center].

BACKGROUND: Endoscopic evaluation plays an indispensable role in medical treatments designed to prevent, diagnose, and cure gastrointestinal disease. Surveillance culture monitoring may be useful in monitoring the outcome of reprocessing. PURPOSE: In this project, microbiologic surveillance cultures were employed to improve the quality of flexible endoscope disinfection. RESOLUTION: This project, implemented from February 1st, 2018 to February 28th, 2019, used several approaches to improve the positive culture rate. We redesigned and implemented the standard operating procedures for endoscope reprocessing, established an in-service training course, provided education materials on reprocessing, and installed a storage cabinet that custom-built to accommodate the endoscope. RESULTS: The positive culture rate was reduced from 5.8% to 0%. CONCLUSIONS: Endoscopy culturing is a useful method to assess the effectiveness of standard reprocessing procedures. The development of guidelines and skill practices should follow current, evidence-based practice and infection prevention principles, and related documents should be organized. We suggest regularly deploying quality-improvement techniques to improve performance and service delivery.

Complete genome sequences of two novel dicistroviruses detected in yellow crazy ants (Anoplolepis gracilipes).

We report two novel RNA viruses from yellow crazy ants, (Anoplolepis gracilipes) detected using next-generation sequencing. The complete genome sequences of the two viruses were 10,662 and 8,238 nucleotides in length, respectively, with both possessing two open reading frames with three conserved protein domains. The genome organization is characteristic of members of the genus Triatovirus in the family Dicistroviridae. The two novel viruses were tentatively named "Anoplolepis gracilipes virus 1" and "Anoplolepis gracilipes virus 2" (AgrV-1 and AgrV-2). Phylogenetic analyses based on amino acid sequences of the non-structural polyprotein (ORF1) suggest that the two viruses are triatovirus-like viruses. This is the first report on the discovery of novel triatovirus-like viruses in yellow crazy ants with a description of their genome structure (two ORFs and conserved domains of RNA helicase, RNA-dependent RNA polymerase, and capsid protein), complete sequences, and viral prevalence across the Asia-Pacific region.

Combining analysis of multi-parametric MR images into a convolutional neural network: Precise target delineation for vestibular schwannoma treatment planning.

Manual delineation of vestibular schwannoma (VS) by magnetic resonance (MR) imaging is required for diagnosis, radiosurgery dose planning, and follow-up tumor volume measurement. A rapid and objective automatic segmentation method is required, but problems have been encountered due to the low through-plane resolution of standard VS MR scan protocols and because some patients have non-homogeneous cystic areas within their tumors. In this study, we retrospectively collected multi-parametric MR images from 516 patients with VS; these were extracted from the Gamma Knife radiosurgery planning system and consisted of T1-weighted (T1W), T2-weighted (T2W), and T1W with contrast (T1W + C) images. We developed an end-to-end deep-learning-based method via an automatic preprocessing pipeline. A two-pathway U-Net model involving two sizes of convolution kernel (i.e., 3 × 3 × 1 and 1 × 1 × 3) was used to extract the in-plane and through-plane features of the anisotropic MR images. A single-pathway model that adopted the same architecture as the two-pathway model, but used a kernel size of 3 × 3 × 3, was also developed for comparison purposes. In addition, we used multi-parametric MR images with different image contrasts as the model training input in order to effectively segment tumors with solid as well as cystic parts. The results of the automatic segmentation demonstrated that (1) the two-pathway model outperformed single-pathway model in terms of dice scores (0.90 ± 0.05 versus 0.87 ± 0.07); both of them having been trained using the T1W, T1W + C and T2W anisotropic MR images, (2) the optimal single-parametric two-pathway model (dice score: 0.88 ± 0.06) was then trained using the T1W + C images, and (3) the two-pathway models trained using bi-parametric (T1W + C and T2W) and tri-parametric (T1W, T2W, and T1W + C) images outperformed the model trained using the single-parametric (T1W + C) images (dice scores: 0.89 ± 0.05 and 0.90 ± 0.05, respectively, larger than 0.88 ± 0.06) because it showed improved segmentation of the non-homogeneous parts of the tumors. The proposed two-pathway U-Net model outperformed the single-pathway U-Net model when segmenting VS using anisotropic MR images. The multi-parametric models effectively improved on the defective segmentation obtained using the single-parametric models by separating the non-homogeneous tumors into their solid and cystic parts.

Synthesis and magnetic characterization of a dinuclear complex of low-coordinate iron(II).

Low-coordinate ions possess exciting magnetic, optical, and reactive properties that may afford novel material physics. Hence, it is important to test both synthetic methods for realizing extended solids of such ions as well as the properties of smaller molecular fragments of envisioned future materials. Herein, we report the synthesis and characterization of a new dinuclear Fe species, [{(Me3Si2)2N}Fe{µ-p-{HN(SiMe3)}(C6Me4){N(SiMe3)}}2Fe{N(SiMe3)2}] (1), formed through a transamination reaction between [Fe{N(SiMe3)2}2]2 and the bulky diamine p-{HN(SiMe3)}2(C6Me4) (L). The Fe centers of this dimer assume a pseudo-trigonal-planar, three-coordinate conformation in 1, bridged by two aromatic diamines. Single-crystal X-ray diffraction, IR spectroscopy, and Mössbauer spectroscopy enable the assignment of both Fe centers as the 2+ oxidation state. Magnetic studies show that 1 displays a weak antiferromagnetic exchange interaction (J = -2.33 cm-1) and moderate zero-field splitting (D = 7.51 cm-1). Importantly, these studies demonstrate the viability of using transamination to bridge high-spin low-coordinate metal ions and hence the technique may, in the future, produce new extended structures.

Comparing the Staging/Restaging Performance of 68Ga-Labeled Prostate-Specific Membrane Antigen and 18F-Choline PET/CT in Prostate Cancer: A Systematic Review and Meta-analysis.

PURPOSE: PET/CT using prostate-specific membrane antigen (PSMA) and choline radiotracers is widely used for diagnosis of prostate cancer. However, the roles of and differences in diagnostic performance between these 2 radiotracers for prostate cancer are unclear. The aim of this study was to compare the staging and restaging performance of Ga-labeled PSMA and F-choline PET/CT imaging in prostate cancer. METHODS: A comprehensive search was performed in PubMed for studies reporting the staging performance of Ga-PSMA and F-choline PET/CT in prostate cancer from the inception of the database to October 1, 2018, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Thirty-five studies were included in this systematic review and meta-analysis. Pooled estimates of patient- and lesion-based sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) for Ga-PSMA and F-choline PET/CT were calculated alongside 95% confidence intervals. Summary receiver operating characteristic curves were plotted, and the area under the summary receiver operating characteristic curve (AUC) was determined alongside the Q* index. RESULTS: The patient-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of Ga-PSMA PET/CT for staging in prostate cancer (13 studies) were 0.92, 0.94, 7.91, 0.14, 79.04, and 0.96, respectively, whereas those of F-choline PET/CT (16 studies) were 0.93, 0.83, 4.98, 0.10, 68.27, and 0.95. The lesion-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of Ga-PSMA PET/CT for staging in prostate cancer (9 studies) were 0.83, 0.95, 23.30, 0.17, 153.58, and 0.94, respectively, and those of F-choline PET/CT (4 studies) were 0.81, 0.92, 8.59, 0.20, 44.82, and 0.98. In both patient- and lesion-based imaging, there was no statistically significant difference in the abilities of detecting or excluding prostate cancer between Ga-PSMA PET/CT and F-choline PET/CT. CONCLUSIONS: For staging and restaging performance in patients with prostate cancer, there was no significant difference between Ga-PSMA PET/CT and F-choline PET/CT. Ga-PSMA PET/CT and F-choline PET/CT have demonstrated high diagnostic performance for accurate staging and restaging in patients with prostate cancer, and thus both should be considered for staging in this disease.

Sintered dicalcium pyrophosphate treatment attenuates estrogen deficiency-associated disc degeneration in ovariectomized rats.

BACKGROUND: Estrogen deficiency is associated with musculoskeletal disorders. Sintered dicalcium pyrophosphate (SDCP) is a novel antiosteoporotic agent. In this study, we examined its use for restoration of bone quality and attenuation of disc degeneration in ovariectomy rats. METHODS: Sixty female Sprague Dawley rats were randomly divided into 3 groups, namely sham group undergoing sham surgery, ovariectomy (OVX) group receiving an equivalent volume of isotonic sodium chloride solution, and OVX/SDCP group orally administered with 0.25 mg/mL SDCP. Animals were sacrificed at 3 and 6 months post ovariectomy and lumbar vertebrae and intervertebral discs were harvested. Bone mineral density, micro-computed tomography analysis, and biomechanical testing were performed to assess bone quality. Histological analysis with hematoxylin and eosin, Alcian blue, and Masson's trichrome stain were conducted to determine disc degeneration. Immunohistochemistry and real-time PCR were carried out to measure the expressions of aggrecan, type I collagen, type II collagen, and MMP-1, MMP-3, and MMP-13. RESULTS: SDCP improved bone quality as observed by the results of increased bone mineral density and stiffness in OVX rats. The improvement in disc degeneration induced by estrogen withdrawal was associated with reduced gene expressions of MMPs and increased production of collagen type II. CONCLUSION: SDCP prevents osteoporosis and ameliorates disc degeneration in OVX rats. It represents a favorable therapeutic agent for osteoporotic and osteoarthritic conditions in clinical practice.

Staging/restaging performance of F18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in breast cancer: A review and meta-analysis.

PURPOSE: This systematic review and meta-analysis was performed to assess the staging/restaging performance of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) in breast cancer. METHODS: A comprehensive search was performed in PubMed databases for studies reporting the staging performance of F18-FDG PET/MRI in breast cancer from the inception of these databases to January 29, 2018. Eight studies were included in this systematic review and meta-analysis. Pooled estimates of patient- and lesion-based sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of F18-FDG PET/MRI were calculated alongside 95% confidence intervals (CIs). A summary receiver operating characteristic curve (SROC) was plotted and the area under the SROC curve (AUC) was determined alongside the Q* index. RESULTS: The patient-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of F18-FDG PET/MRI for staging in breast cancer were 0.98 (95% CI, 0.95-0.99), 0.87 (95% CI, 0.76-0.95), 4.59 (95% CI, 1.91-11.05), 0.03 (95% CI, 0.01-0.09), 203.07 (95% CI, 50.33-819.38), and 0.99, respectively. The lesion-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of F18-FDG PET/MRI for staging in breast cancer were 0.91 (95% CI, 0.88-0.94), 0.95 (95% CI, 0.92-0.97), 11.28 (95% CI, 4.25-29.96), 0.07 (95% CI, 0.02-0.22), 286.46 (95% CI, 64.15-1279.17), and 0.99, respectively. The overall diagnostic accuracies (Q* index) of the staging performance of F18-FDG PET/MRI in breast cancer were 0.96 (patient-based analysis) and 0.95 (lesion-based analysis). CONCLUSION: F18-FDG PET/MRI has excellent diagnostic staging/restaging performance in patients with breast cancer, and thus should be considered for staging of patients with breast cancer.