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Background: Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer‐related death in the United States. However, early response assessment using the current approach of measuring changes in tumor size on computed tomography (CT) or MRI is challenging. Purpose: To investigate the feasibility of hyperpolarized (HP) [1‐13C]pyruvate MRI to quantify metabolism in the normal appearing pancreas and PDA, and to assess changes in PDA metabolism following systemic chemotherapy. Study Type: Prospective. Subjects: Six patients (65.0 ± 7.6 years, 2 females) with locally advanced or metastatic PDA enrolled prior to starting a new line of systemic chemotherapy. Field Strength/Sequence: 3‐T, T1‐weighted gradient echo, metabolite‐selective 13C echoplanar imaging. Assessment: Time‐resolved HP [1‐13C]pyruvate data were acquired before (N = 6) and 4‐weeks after (N = 3) treatment initiation. Pyruvate metabolism, as quantified by pharmacokinetic modeling and metabolite area‐under‐the‐curve ratios, was assessed in manually segmented PDA and normal appearing pancreas ROIs (N = 5). The change in tumor metabolism before and 4‐weeks after treatment initiation was assessed in primary PDA (N = 2) and liver metastases (N = 1), and was compared to objective tumor response defined by response evaluation criteria in solid tumors (RECIST) on subsequent CTs. Statistical Tests: Descriptive tests (mean ± standard deviation), model fit error for pharmacokinetic rate constants. Results: Primary PDA showed reduced alanine‐to‐lactate ratios when compared to normal pancreas, due to increased lactate‐to‐pyruvate or reduced alanine‐to‐pyruvate ratios. Of the three patients who received HP [1‐13C]pyruvate MRI before and 4‐weeks after treatment initiation, one patient had a primary tumor with early metabolic response (increase in alanine‐to‐lactate) and subsequent partial response according to RECIST, one patient had a primary tumor with relatively stable metabolism and subsequent stable disease by RECIST, and one patient had metastatic PDA with increase in lactate‐to‐pyruvate of the liver metastases and corresponding progressive disease according to RECIST. Data Conclusion: Altered pyruvate metabolism with increased lactate or reduced alanine was observed in the primary tumor. Early metabolic response assessed at 4‐weeks after treatment initiation correlated with subsequent objective tumor response assessed using RECIST. Level of Evidence: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: Blood transfusion (BT) may be associated with an increased risk of thromboembolism. The associations between transfusion reactions (TRs) during BTs and potential risk factors for the development of thromboembolism in patients underwent blood transfusion have not been analyzed. Therefore, this study aimed to compare risk factors associated with the development of venous thromboembolism (VTE) or pulmonary embolism (PE) between patients underwent blood transfusion with and without TRs. Study Designs and Methods: The retrospective study was conducted between April 1, 2017, and March 31, 2020, at a medical center in Taiwan. Blood‐transfused patients were grouped into two cohorts as follows: those who experienced TRs and those who did not experience TRs. Both cohorts were subjected to follow‐up until March 31, 2021. The endpoints for both groups were the occurrence of VTE or PE or the date of March 31, 2021. To investigate between‐cohort risk differences, a Kaplan–Meier survival analysis and multiple Cox proportional hazard model was used. Results: A total of 10,759 patients underwent 59,385 transfusion procedures, with 703 patients in the TR group, and 10,056 patients in the non‐TR group. The risk of VTE or PE was twice as high in the TR group than in the non‐TR group (adjusted hazard ratio 2.53, 95% confidence interval 1.49–4.29, p =.001). Meanwhile, age, female sex, transfusion frequency increment, and being nondiabetic was associated with an increased risk of developing thromboembolism. Conclusion: TRs are associated with increased long‐term thromboembolism risk in patients underwent blood transfusion. It is imperative for clinicians to acknowledge this and maintain rigorous follow‐up. [ABSTRACT FROM AUTHOR]

Paclitaxel induces multipolar spindles at clinically relevant doses but does not substantially increase mitotic indices. Paclitaxel's anti-cancer effects are hypothesized to occur by promoting chromosome mis-segregation on multipolar spindles leading to apoptosis, necrosis and cyclic-GMP-AMP Synthase–Stimulator of Interferon Genes (cGAS-STING) pathway activation in daughter cells, leading to secretion of type I interferon (IFN) and immunogenic cell death. Eribulin and vinorelbine have also been reported to cause increases in multipolar spindles in cancer cells. Recently, suppression of Anaphase-Promoting Complex/Cyclosome–Cell Division Cycle 20 (APC/C-CDC20) activity using CRISPR/Cas9 mutagenesis has been reported to increase sensitivity to Kinesin Family 18a (KIF18a) inhibition, which functions to suppress multipolar mitotic spindles in cancer cells. We propose that a way to enhance the effectiveness of anti-cancer agents that increase multipolar spindles is by suppressing the APC/C-CDC20 to delay, but not block, anaphase entry. Delaying anaphase entry in genomically unstable cells may enhance multipolar spindle-induced cell death. In genomically stable healthy human cells, delayed anaphase entry may suppress the level of multipolar spindles induced by anti-cancer drugs and lower mitotic cytotoxicity. We outline specific combinations of molecules to investigate that may achieve the goal of enhancing the effectiveness of anti-cancer agents. [ABSTRACT FROM AUTHOR]

Purpose: Improving the quality and maintaining the fidelity of large coverage abdominal hyperpolarized (HP) 13C MRI studies with a patch based global–local higher‐order singular value decomposition (GL‐HOVSD) spatiotemporal denoising approach. Methods: Denoising performance was first evaluated using the simulated [1‐13C]pyruvate dynamics at different noise levels to determine optimal kglobal and klocal parameters. The GL‐HOSVD spatiotemporal denoising method with the optimized parameters was then applied to two HP [1‐13C]pyruvate EPI abdominal human cohorts (n = 7 healthy volunteers and n = 8 pancreatic cancer patients). Results: The parameterization of kglobal = 0.2 and klocal = 0.9 denoises abdominal HP data while retaining image fidelity when evaluated by RMSE. The kPX (conversion rate of pyruvate‐to‐metabolite, X = lactate or alanine) difference was shown to be <20% with respect to ground‐truth metabolic conversion rates when there is adequate SNR (SNRAUC > 5) for downstream metabolites. In both human cohorts, there was a greater than nine‐fold gain in peak [1‐13C]pyruvate, [1‐13C]lactate, and [1‐13C]alanine apparent SNRAUC. The improvement in metabolite SNR enabled a more robust quantification of kPL and kPA. After denoising, we observed a 2.1 ± 0.4 and 4.8 ± 2.5‐fold increase in the number of voxels reliably fit across abdominal FOVs for kPL and kPA quantification maps. Conclusion: Spatiotemporal denoising greatly improves visualization of low SNR metabolites particularly [1‐13C]alanine and quantification of [1‐13C]pyruvate metabolism in large FOV HP 13C MRI studies of the human abdomen. [ABSTRACT FROM AUTHOR]

Understanding drought evolution and its driving factors is crucial for effective water resource management and forecasting. This study enhances the analysis of drought probability by constructing bivariate distributions, providing a more realistic perspective than single-characteristic approaches. Additionally, a meteorological drought migration model is established to explore spatiotemporal paths and related characteristics of major drought events in the Choushui River alluvial fan. The results reveal a significant increase in the probability of southward-moving drought events after 1981. Before 1981, drought paths were diverse, while after 1981, these paths became remarkably similar, following a trajectory from north to south. This is primarily attributed to the higher rainfall in the northern region of the Choushui River alluvial fan from February to April, leading to a consistent southward movement of drought centroids. This study proposes that climate change is a primary factor influencing changes in the spatiotemporal paths of drought. It implies that changes in rainfall patterns and climate conditions can be discerned through the meteorological drought migration model. As a result, it provides the potential for simplifying drought-monitoring methods. These research findings provide further insight into the dynamic process of drought in the Choushui River alluvial fan and serve as valuable references for future water resource management. [ABSTRACT FROM AUTHOR]

Introduction: The healthy heart has remarkable metabolic flexibility that permits rapid switching between mitochondrial glucose oxidation and fatty acid oxidation to generate ATP. Loss of metabolic flexibility has been implicated in the genesis of contractile dysfunction seen in cardiomyopathy. Metabolic flexibility has been imaged in experimental models, using hyperpolarized (HP) [2‐13C]pyruvate MRI, which enables interrogation of metabolites that reflect tricarboxylic acid (TCA) cycle flux in cardiac myocytes. This study aimed to develop methods, demonstrate feasibility for [2‐13C]pyruvate MRI in the human heart for the first time, and assess cardiac metabolic flexibility. Methods: Good manufacturing practice [2‐13C]pyruvic acid was polarized in a 5 T polarizer for 2.5–3 h. Following dissolution, quality control parameters of HP pyruvate met all safety and sterility criteria for pharmacy release, prior to administration to study subjects. Three healthy subjects each received two HP injections and MR scans, first under fasting conditions, followed by oral glucose load. A 5 cm axial slab‐selective spectroscopy approach was prescribed over the left ventricle and acquired at 3 s intervals on a 3 T clinical MRI scanner. Results: The study protocol, which included HP substrate injection, MR scanning, and oral glucose load, was performed safely without adverse events. Key downstream metabolites of [2‐13C]pyruvate metabolism in cardiac myocytes include the glycolytic derivative [2‐13C]lactate, TCA‐associated metabolite [5‐13C]glutamate, and [1‐13C]acetylcarnitine, catalyzed by carnitine acetyltransferase (CAT). After glucose load, 13C‐labeling of lactate, glutamate, and acetylcarnitine from 13C‐pyruvate increased by an average of 39.3%, 29.5%, and 114% respectively in the three subjects, which could result from increases in lactate dehydrogenase, pyruvate dehydrogenase, and CAT enzyme activity as well as TCA cycle flux (glucose oxidation). Conclusions: HP [2‐13C]pyruvate imaging is safe and permits noninvasive assessment of TCA cycle intermediates and the acetyl buffer, acetylcarnitine, which is not possible using HP [1‐13C]pyruvate. Cardiac metabolite measurement in the fasting/fed states provides information on cardiac metabolic flexibility and the acetylcarnitine pool. [ABSTRACT FROM AUTHOR]

Simple Summary: Dynamic hyperpolarized carbon-13 (HP-13C) MRI is a novel molecular imaging technique that allows for real-time in vivo imaging of glycolysis and oxidative phosphorylation using [1-13C]pyruvate as a non-radioactive and non-toxic metabolic probe. While HP-13C MRI has recently demonstrated the potential to capture Warburg-related metabolic dysregulation in patients with progressive/treatment-naïve high-grade gliomas, further improvement in methodologies is still necessary to help monitor disease status and evaluate early predictors of therapeutic response. To this end, a multimodal 1H/HP-13C MRI protocol was implemented in this study, which incorporated advanced brain tumor MR acquisitions and improved HP-13C metabolic imaging methodologies for the serial monitoring of patients with glioma over the course of clinical treatment. This study aimed to implement a multimodal 1H/HP-13C imaging protocol to augment the serial monitoring of patients with glioma, while simultaneously pursuing methods for improving the robustness of HP-13C metabolic data. A total of 100 1H/HP [1-13C]-pyruvate MR examinations (104 HP-13C datasets) were acquired from 42 patients according to the comprehensive multimodal glioma imaging protocol. Serial data coverage, accuracy of frequency reference, and acquisition delay were evaluated using a mixed-effects model to account for multiple exams per patient. Serial atlas-based HP-13C MRI demonstrated consistency in volumetric coverage measured by inter-exam dice coefficients (0.977 ± 0.008, mean ± SD; four patients/11 exams). The atlas-derived prescription provided significantly improved data quality compared to manually prescribed acquisitions (n = 26/78; p = 0.04). The water-based method for referencing [1-13C]-pyruvate center frequency significantly reduced off-resonance excitation relative to the coil-embedded [13C]-urea phantom (4.1 ± 3.7 Hz vs. 9.9 ± 10.7 Hz; p = 0.0007). Significantly improved capture of tracer inflow was achieved with the 2-s versus 5-s HP-13C MRI acquisition delay (p = 0.007). This study demonstrated the implementation of a comprehensive multimodal 1H/HP-13C MR protocol emphasizing the monitoring of steady-state/dynamic metabolism in patients with glioma. [ABSTRACT FROM AUTHOR]

A same-brand bottled food sold by competing retailers may be produced in different countries. This investigation offers an empirically-based view of how consumers evaluate a bi-national bottled food product which carries a brand associated with a developed country but is manufactured in a developing country, as opposed to its home-country-made variants; and also seeks to identify extrinsic product cues which may moderate their responses. Results show that perceived quality erodes because of an off-putting COM image, while a short shelf life improves its evaluation. Such effect, however, is limited to small-size and glass packaging. In addition, shoppers' product quality perceptions raise their willingness to pay. [ABSTRACT FROM AUTHOR]

Background and Objectives: Treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) must deal with immunosuppression, as well as infections associated with a compromised immune system, such as tuberculosis (TB). Our aim was to examine the risk of incidental TB after diagnosis of AAV. Materials and Methods: This retrospective population-based cohort study was based on the data from the National Health Insurance Research Database in Taiwan. Patients with newly diagnosed granulomatous polyangiitis or microscopic polyangiitis were identified between 1 January 2000 and 31 December 2012. The primary outcome was risk of incidental TB. Cox proportional hazard models were used to evaluate the association between AAV and incidental TB. Results: A total of 2257 patients with AAV and a propensity-score matched cohort of 9028 patients were studied. Overall, patients with AAV were at a 1.48× higher risk of contracting incidental TB than the patients in the matched cohort (adjusted HR 1.48; 95% confidence interval [CI], 1.02–2.15). Note that the highest risk of contracting incidental TB was in the first two years following a diagnosis of AAV, with a nearly 1-fold increase in risk (adjusted HR, 1.91; 95% CI, 1.01–3.60). Female AAV patients were 3.24× more likely than females without AAV to develop TB (adjusted HR 3.24; 95% CI, 1.85–5.67). Conclusions: Patients with AAV exhibit a 48% elevated TB risk, notably, a 91% increase within the first two years postdiagnosis. Female AAV patients face a 3.24 times higher TB risk compared to females without AAV. This study is limited by potential misclassification and overestimation of AAV cases. Clinicians should closely monitor TB risk in AAV patients, especially in females and the initial two years following diagnosis. [ABSTRACT FROM AUTHOR]

A universal health insurance program such as the National Health Insurance in Taiwan offers a wide coverage and increased access to healthcare services. Despite its ongoing efforts to enhance healthcare accessibility, differences in health for people living in urban and resource-deprived areas remain substantial. To investigate the longitudinal impact of the healthcare system and other potential structural drivers such as education and economic development on geographical disparities in health, we designed a panel study with longitudinal open secondary data, covering all 368 townships in Taiwan between 2013 and 2017. Our findings indicated higher mortality rates in the mountainous and rural areas near the east and south regions of the island in both years. Multivariate analyses showed an increase in the density of primary care physicians (PCP) was associated with lower all-cause mortality (β = − 0.72, p < 0.0001) and cardiovascular disease mortality (β = − 0.41, p < 0.0001). Effect of PCP is evident, but merely focusing on access to healthcare is still not enough. Additional measures are warranted to address the health disparities existing between urban and underprivileged areas. [ABSTRACT FROM AUTHOR]

A universal health insurance program such as the National Health Insurance in Taiwan offers a wide coverage and increased access to healthcare services. Despite its ongoing efforts to enhance healthcare accessibility, differences in health for people living in urban and resource-deprived areas remain substantial. To investigate the longitudinal impact of the healthcare system and other potential structural drivers such as education and economic development on geographical disparities in health, we designed a panel study with longitudinal open secondary data, covering all 368 townships in Taiwan between 2013 and 2017. Our findings indicated higher mortality rates in the mountainous and rural areas near the east and south regions of the island in both years. Multivariate analyses showed an increase in the density of primary care physicians (PCP) was associated with lower all-cause mortality (β = − 0.72, p < 0.0001) and cardiovascular disease mortality (β = − 0.41, p < 0.0001). Effect of PCP is evident, but merely focusing on access to healthcare is still not enough. Additional measures are warranted to address the health disparities existing between urban and underprivileged areas. [ABSTRACT FROM AUTHOR]

The development of civilization and the preservation of environmental ecosystems are strongly dependent on water resources. Typically, an insufficient supply of surface water resources for domestic, industrial, and agricultural needs is supplemented with groundwater resources. However, groundwater is a natural resource that must accumulate over many years and cannot be recovered after a short period of recharge. Therefore, the long-term management of groundwater resources is an important issue for sustainable development. The accurate prediction of groundwater levels is the first step in evaluating total water resources and their allocation. However, in the process of data collection, data may be lost due to various factors. Filling in missing data is a main problem that any research field must address. It is well known that to maintain data integrity, one effective approach is missing value imputation (MVI). In addition, it has been demonstrated that machine learning may be a better tool. Therefore, the main purpose of this study was to utilize a generative adversarial network (GAN) that consists of a generative model and a discriminative model for imputation. Although the GAN could not capture the groundwater level endpoints in every section, the overall simulation performance was still excellent to some extent. Our results show that the GAN can improve the accuracy of water resource evaluations. In the current study, two interdisciplinary deep learning methods, univariate and Seq2val (sequence-to-value), were used for groundwater level estimation. In addition to addressing the significance of the parameter conditions, the advantages and disadvantages of these two models in hydrological simulations were also discussed and compared. Regarding parameter selection, the simulation results for univariate analysis were better than those for Seq2val analysis. Finally, univariate was employed to examine the limits of the models in long-term water level simulations. Our results suggest that the accuracy of CNNs is better, while LSTM is better for the simulation of multistep prediction. Therefore, the interdisciplinary deep learning approach may be beneficial for providing a better evaluation of water resources. [ABSTRACT FROM AUTHOR]

China and Taiwan (so‐called Greater China) are representative of two of the fastest‐growing economies in the Pacific Rim region. This study uses Taiwanese high‐tech firms as sample and explores whether boards of directors attempt to avoid opportunistic reductions in research and development (R&D) investments by CEOs. This study considers a scenario in which high‐tech firms face a small earnings decline or a small loss but their CEOs could opportunistically cut R&D investments to improve financial results. The focus of this study is to examine how corporate control (whether or not a firm is controlled by a family) and market competition affect the relationship between R&D investments and CEO compensation schemes. Overall, we find that the stock‐based incentive compensation is more effective than the cash compensation in deterring managerial opportunism. In non‐family firms, we find there exists a positive significant relationship between changes in R&D expenditures and changes in CEO stock‐based compensation when a firm is faced with a small earnings decline or a small loss. Specifically, compared to family firms, the boards of directors of non‐family firms face more severe agency problems (as a result of the separation of ownership and control) and therefore tend to significantly adjust the incentive components in CEO compensation schemes to deter managerial opportunism. Regarding the effect of market competition, we find that incentives to adjust compensation plan to remove CEOs from opportunistically reducing discretionary R&D investments are greater in firms facing more intense market competition. [ABSTRACT FROM AUTHOR]

Colorism—systematic intragroup discrimination based on skin color—uniquely affects African American women. Using a sequential mixed methods design, this study explored perceptions of colorism and sun-related behavior among African American women in college. Study 1, which included 14 in-depth interviews, revealed perceptions that lighter skin is mostly preferred among African American women and that this preference can influence sun-related behavior. Study 2 featured a self-administered questionnaire (n = 187) based on interview commentary. Findings indicated an internalized status quo: Participants deemed colorism prevalent among African Americans and believed that preferences for lighter skin influenced daily life, including sun avoidance. Personal skin color preferences were less clear than participants' perceptions of others' preferences. Results pinpointed a possible connection between colorism and sun-related behavior, unveiling interrelationships among internalized beliefs, subjective norms, and behavior. Understanding colorism's entrenched role and the social context of sun-related decisions extends colorism research from the psychosocial realm to the behavioral. Implications can increase practitioners' awareness of colorism, enabling interventions to promote appropriate health education and wellbeing among African American women. [ABSTRACT FROM AUTHOR]

Purpose: Model‐constrained reconstruction with Fourier‐based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1‐13C]‐pyruvate. Methods: The MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single‐channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity of reconstructed metabolite time series. Results: All three data sets showed successful reconstruction using MoReFUn. In simulation and retrospective phantom data, the restored time series of pyruvate and lactate maintained the image details, and the mean square residual error of the accelerated reconstruction increased only slightly (< 10%) at a reduction factor up to 8. In prostate data, the quantitative estimation of the conversion‐rate constant of pyruvate to lactate was achieved with high accuracy of less than 10% error at a reduction factor of 2 compared with the conversion rate derived from unaccelerated data. Conclusion: The MoReFUn technique can be used as an effective and reliable imaging acceleration method for metabolic imaging using hyperpolarized [1‐13C]‐pyruvate. [ABSTRACT FROM AUTHOR]

Background: Research investigating differences in the overall stroke risk between individuals with and without immune thrombocytopenia (ITP) is lacking. Methods: This real-world study used the National Health Insurance Research Database (NHIRD). Risk of stroke was compared between 13,085 individuals with ITP enrolled between 1 January 2000 and 31 December 2015 and a control cohort of 52,340 individuals without ITP (1:4 ratio propensity score–matched by age, sex, index year, relevant comorbidities, and medications). Sub-distribution hazards models were used to estimate adjusted sub-distribution hazard ratio (SHR) and 95% confidence intervals (CIs), with the non-ITP group as the control group. Results: Of the 65,425 participants, 13,085 had ITP, 63.3% were women, and the mean age was 52.59 years. The risk of both ischemic and hemorrhagic stroke was 1.14 times (adjusted SHR 1.14, 95% CI, 1.07–1.22) and 1.93 times (adjusted SHR 1.93, 95% CI, 1.70–2.20) higher in the ITP group than in controls. Patients with ITP in the 20- to 29-year subgroup had a higher risk of new-onset stroke (adjusted SHR, 4.06 (95% CI, 2.72–6.07), p value for interaction <0.01) than those aged 20–29 years without ITP. Individuals with severe ITP with splenectomy had a 1.79 times higher overall stroke risk than those without. Conclusions: ITP is associated with increased risk of both ischemic and hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Owing to active orogenic movement and the monsoon climate, rainfall-induced landslide disasters often occur in Taiwan. Hence, hillslope hydrology and stability have received considerable research attention. However, it remains difficult to accurately estimate the duration and consequences of hillslope instability induced by hillslope hydrology. Research on hillslope hydrology and stability is complicated by spatial heterogeneity, hydrological processes operating at various scales, spatiotemporal evolution, and geomorphological properties. Recent advances in critical zone science have provided an approach to extend geoscience studies. The "deep coupling" concept is essential for integrating physical, chemical, and biological processes on various spatiotemporal scales and for providing a macro and unified framework for evaluating internal properties and processes. Critical zone science and hillslope hydrology and stability both depend on interdisciplinary perspectives and approaches, monitoring strategies, and model analysis of integrating and coupling processes. They both share the characteristics of spatial heterogeneity, continuous evolution, and relevance to ecosystem services. To address the challenges related to hillslope hydrology and stability in Taiwan, we reviewed the progress in, relevance between, and common challenges to hillslope hydrology, stability, and critical zone science. We then presented a process-based integrated monitoring strategy, an interdisciplinary perspective, and a coupling analysis framework and model. The aim of this study was to promote the advancement of research on hillslope stability and hydrology in Taiwan. [ABSTRACT FROM AUTHOR]

Baseflow is among the most important components of streamflow. It is the main source of streamflow from groundwater systems in the dry season and also plays an important role as a water resource in the ecological environment and for human activities. In recent years, because of climate change, the number of dry season days in Taiwan has increased, and the wet season has been delayed, resulting in fewer rainy days and increased precipitation intensity. In addition, the spatial distribution of rainfall is uneven, and rivers are short and fast-flowing. Taiwan has become a country with abundant rainfall but insufficient water resources; therefore, the assessment of baseflow is important. This study selected eight basins with distinct wet and dry seasons in southern Taiwan as the study area. The baseflow characteristics and their relationships with climate features were assessed using time series analysis, baseflow attribution analysis, and wavelet analysis. The results showed that baseflow has an increasing trend; both precipitation and evapotranspiration have a significant positive correlation with baseflow, and the impact of precipitation is greater than that of evaporation. Sensitivity analysis showed that baseflow increases with increasing evaporation and precipitation; this behavior is related to the concentration of precipitation and evaporation in the wet season. Baseflow attribution analysis showed that the contribution of climate change to baseflow (75.0%) was larger than that of human activities (−2.9%), indicating that climate change was the main factor in the increase in baseflow. Wavelet analysis showed that both the El Niño–Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) are correlated with baseflow, where the PDO is more strongly correlated than the ENSO. The main timescales of the ENSO and PDO are a 4–8-year band and an 8-year band, respectively. The ENSO may have a timescale above the 8-year band, and the PDO exhibits periodic correlation changes at a 1-year band. [ABSTRACT FROM AUTHOR]

Purpose: To develop techniques and establish a workflow using hyperpolarized carbon‐13 (13C) MRI and the pyruvate‐to‐lactate conversion rate (kPL) biomarker to guide MR‐transrectal ultrasound fusion prostate biopsies. Methods: The integrated multiparametric MRI (mpMRI) exam consisted of a 1‐min hyperpolarized 13C‐pyruvate EPI acquisition added to a conventional prostate mpMRI exam. Maps of kPL values were calculated, uploaded to a picture archiving and communication system and targeting platform, and displayed as color overlays on T2‐weighted anatomic images. Abdominal radiologists identified 13C research biopsy targets based on the general recommendation of focal lesions with kPL >0.02(s−1), and created a targeting report for each study. Urologists conducted transrectal ultrasound‐guided MR fusion biopsies, including the standard 1H–mpMRI targets as well as 12–14 core systematic biopsies informed by the research 13C‐kPL targets. All biopsy results were included in the final pathology report and calculated toward clinical risk. Results: This study demonstrated the safety and technical feasibility of integrating hyperpolarized 13C metabolic targeting into routine 1H–mpMRI and transrectal ultrasound fusion biopsy workflows, evaluated via 5 men (median age 71 years, prostate‐specific antigen 8.4 ng/mL, Cancer of the Prostate Risk Assessment score 2) on active surveillance undergoing integrated scan and subsequent biopsies. No adverse event was reported. Median turnaround time was less than 3 days from scan to 13C‐kPL targeting, and scan‐to‐biopsy time was 2 weeks. Median number of 13C targets was 1 (range: 1–2) per patient, measuring 1.0 cm (range: 0.6–1.9) in diameter, with a median kPL of 0.0319 s−1 (range: 0.0198–0.0410). Conclusions: This proof‐of‐concept work demonstrated the safety and feasibility of integrating hyperpolarized 13C MR biomarkers to the standard mpMRI workflow to guide MR‐transrectal ultrasound fusion biopsies. [ABSTRACT FROM AUTHOR]

A lab-fabricated ocean bottom seismometer was modified and deployed terrestrially to detect low-frequency (<10 Hz) ground vibrations produced by debris flows. A frequency–response test of the new seismometer revealed that it can detect seismic signals at frequencies of 0.3–120 Hz. Its seismic ground motion detection ability was investigated by comparing its measurements of seismic signals produced by rockfalls with those of a geophone. Two new seismometers were deployed at the Aiyuzi Stream, Nantou County, Taiwan, in September 2012. Seismic signals produced by two local earthquakes, two teleseisms, and three debris flows detected by the seismometer in 2013 and 2014 were discussed. The seismic signal frequencies of the local earthquakes and teleseisms (both approximately 1800 km apart) were 0.3–30 and <1 Hz, respectively. Moreover, seismometer measurements revealed that seismic signals generated by debris flows can have minimum frequencies as low as 2 Hz. Time-matched CCD camera images revealed that debris flow surge fronts with larger rocks have lower minimum frequencies. Finally, because the seismometer can detect low-frequency seismic waves with low spatial decay rates, it was able to detect one debris flow approximately 3 min and 40 s before it arrived. [ABSTRACT FROM AUTHOR]

Background: Patients with idiopathic minimal change nephrotic syndrome (MCNS) undergoing immunosuppressive therapy are susceptible to infectious complications. Study specifically focusing on adult population's infectious complications is lacking. Methods: We retrospectively collected 101 adult patients with biopsy‐proven idiopathic MCNS and analysed for the infectious complications. Published literatures were also reviewed aiming to evaluate the feasibility of prophylactic antibiotic treatment. Results: Infectious complications developed in 17 of 101 (16.8%) patients, with pneumonia (n = 4), cellulitis/fasciitis (n = 4) and urinary tract infection (UTI) (n = 4) being the dominant diseases, and Gram‐negative bacilli the main cause. AKI stage ≥2 (Hazard ratio = 6.1; 95% CI: 1.2–31.9, p = 0.031) and non‐remission by treatment (Hazard ratio = 4.4; 95% CI: 1.2–15.6, p =.023) were the two independent risk factors relevant to developing infectious complications. Review of 16 published literatures and our data showed that even no prophylactic antibiotic therapy, only one case of Pneumocystis jirovecii pneumonia developed among the 1787 accumulative cases of MCNS. In contrast, 16 (44%) of acute flare cases were reported among the 36 patients with positive hepatitis B surface antigen that did not receive antiviral prophylactic therapy. Conclusions: Advanced acute kidney injury and non‐remission by treatment are the risk factors toward developing infectious complications in adult MCNS undergoing immunosuppressive therapy. It appears unnecessary to use prophylactic antibiotic for Pneumocystis jirovecii pneumonia or other bacterial infections, while screening and prophylactic therapy for hepatitis B and latent tuberculosis are critical for patients in prevalent area. Summary at a Glance: Advanced acute kidney injury and poor treatment response are independent risk factors relevant to developing infectious complications in adult patients with idiopathic minimal change nephrotic syndrome. It appears unnecessary to use prophylactic antibiotic for Pneumocystis jirovecii pneumonia or other bacterial infections, while screening and prophylactic therapy for hepatitis B and latent tuberculosis are critical for patients in prevalent area. [ABSTRACT FROM AUTHOR]

Background: Hyperpolarized 13C MRI quantitatively measures enzyme‐catalyzed metabolism in cancer and metabolic diseases. Whole‐abdomen imaging will permit dynamic metabolic imaging of several abdominal organs simultaneously in healthy and diseased subjects. Purpose: Image hyperpolarized [1‐13C]pyruvate and products in the abdomens of healthy volunteers, overcoming challenges of motion, magnetic field variations, and spatial coverage. Compare hyperpolarized [1‐13C]pyruvate metabolism across abdominal organs of healthy volunteers. Study Type: Prospective technical development. Subjects: A total of 13 healthy volunteers (8 male), 21–64 years (median 36). Field Strength/Sequence: A 3 T. Proton: T1‐weighted spoiled gradient echo, T2‐weighted single‐shot fast spin echo, multiecho fat/water imaging. Carbon‐13: echo‐planar spectroscopic imaging, metabolite‐specific echo‐planar imaging. Assessment: Transmit magnetic field was measured. Variations in main magnetic field (ΔB0) determined using multiecho proton acquisitions were compared to carbon‐13 acquisitions. Changes in ΔB0 were measured after localized shimming. Improvements in metabolite signal‐to‐noise ratio were calculated. Whole‐organ regions of interests were drawn over the liver, spleen, pancreas, and kidneys by a single investigator. Metabolite signals, time‐to‐peak, decay times, and mean first‐order rate constants for pyruvate‐to‐lactate (kPL) and alanine (kPA) conversion were measured in each organ. Statistical Tests: Linear regression, one‐sample Kolmogorov–Smirnov tests, paired t‐tests, one‐way ANOVA, Tukey's multiple comparisons tests. P ≤ 0.05 considered statistically significant. Results: Proton ΔB0 maps correlated with carbon‐13 ΔB0 maps (slope = 0.93, y‐intercept = −2.88, R2 = 0.73). Localized shimming resulted in mean frequency offset within ±25 Hz for all organs. Metabolite SNR significantly increased after denoising. Mean kPL and kPA were highest in liver, followed by pancreas, spleen, and kidneys (all comparisons with liver were significant). Data Conclusion: Whole‐abdomen coverage with hyperpolarized carbon‐13 MRI was feasible despite technical challenges. Multiecho gradient echo 1H acquisitions accurately predicted chemical shifts observed using carbon‐13 spectroscopy. Carbon‐13 acquisitions benefited from local shimming. Metabolite energetics in the abdomen compiled for healthy volunteers can be used to design larger clinical trials in patients with metabolic diseases. Evidence Level: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease accompanied with severe itching and skin lesions. Current studies have demonstrated that probiotics can exert an immunomodulatory effect, improve epithelial barrier function, and normalize the composition of gut microbiota. Thus, the aim of this study was to investigate the effect of probiotics on the immune balance of AD in vivo. We first screened two lactic acid bacteria strains, which were Lactococcus lactis subsp. cremoris MP01 and Lactobacillus paracasei subsp. paracasei MP02, from 10 strains isolated from traditional fermented milk with inflammation regulating activities in vitro. In the house dust mite (HDM) extraction-induced AD mouse model, mice were assigned randomly to four groups: control group (PC), HDM-induced AD group (NC), HDM-induced AD mice with administration of a mixture of heat-killed MP01 and MP02 at a low concentration (LD), and high concentration (HD) groups. Compared with the NC group, the probiotic treatments could relieve the AD symptoms. Moreover, the LD group significantly decreased total and HDM-specific IgE concentration. These results indicated that a combination of heat-killed MP01 and MP02 strains modulated the proportion of IL4+CD4+ T cells and IFNγ+CD4+ T cells in the spleen of HDM extraction-induced AD mice. In conclusion, administration of the heat-killed MP01 and MP02 mixtures appeared to relieve the classic AD signs, decrease serum IgE concentration, and rebalance the population of Th1/Th2 cells in HDM extraction-induced AD mice. The immunomodulatory activities of a combination of heat-killed MP01 and MP02 provided a potential new therapeutic strategy against AD. [ABSTRACT FROM AUTHOR]

This study investigates the impact of international diversification on the lag effect of R&D performance for implementing an international diversification strategy. The study uses the sales base amount and the number of countries, respectively, to explain the depth and breadth of international diversification. The results suggest that the higher the level of international diversification, the more profound the positive impact of the international diversification on the R&D activities‐derived operating performance. The study also confirms that companies with broader international diversification have a higher positive R&D lag effect. The empirical results are robust to the problem of endogeneity. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to develop and demonstrate the in vivo feasibility of a 3D stack‐of‐spiral balanced steady‐state free precession(3D‐bSSFP) urea sequence, interleaved with a metabolite‐specific gradient echo (GRE) sequence for pyruvate and metabolic products, for improving the SNR and spatial resolution of the first hyperpolarized 13C‐MRI human study with injection of co‐hyperpolarized [1‐13C]pyruvate and [13C,15N2]urea. Methods: A metabolite‐specific bSSFP urea imaging sequence was designed using a urea‐specific excitation pulse, optimized TR, and 3D stack‐of‐spiral readouts. Simulations and phantom studies were performed to validate the spectral response of the sequence. The image quality of urea data acquired by the 3D‐bSSFP sequence and the 2D‐GRE sequence was evaluated with 2 identical injections of co‐hyperpolarized [1‐13C]pyruvate and [13C,15N2]urea formula in a rat. Subsequently, the feasibility of the acquisition strategy was validated in a prostate cancer patient. Results: Simulations and phantom studies demonstrated that 3D‐bSSFP sequence achieved urea‐only excitation, while minimally perturbing other metabolites (<1%). An animal study demonstrated that compared to GRE, bSSFP sequence provided an ∼2.5‐fold improvement in SNR without perturbing urea or pyruvate kinetics, and bSSFP approach with a shorter spiral readout reduced blurring artifacts caused by J‐coupling of [13C,15N2]urea. The human study demonstrated the in vivo feasibility and data quality of the acquisition strategy. Conclusion: The 3D‐bSSFP urea sequence with a stack‐of‐spiral acquisition demonstrated significantly increased SNR and image quality for [13C,15N2]urea in co‐hyperpolarized [1‐13C]pyruvate and [13C,15N2]urea imaging studies. This work lays the foundation for future human studies to achieve high‐quality and high‐SNR metabolism and perfusion images. [ABSTRACT FROM AUTHOR]

Research investigating incident malignancy risk in erythropoiesis‐stimulating agent (ESA) users with chronic kidney disease (CKD) is lacking. We aimed to compare the incident cancer risk between ESA and non‐ESA users with CKD or end‐stage renal disease (ESRD). In this retrospective cohort study, all adults newly diagnosed with CKD or ESRD between 2000 and 2012 were enrolled. The study population included 98,748 patients. After case–control matching, 7115 patients were included. The defined daily dose (DDD) of ESA was used as the unit for measuring the amount of ESA prescribed. The primary outcome was the risk of incident malignancy. The secondary outcomes were incident malignancy risk in different tertiles of cumulative ESA doses and the risk of different types of cancers. The risk of incident malignancy was 1.84 times higher with ESA treatment than without ESA treatment (hazard ratio, 1.84; 95% confidence interval, 1.43–2.36; p < 0.001). The malignancy risk was positively correlated with the cumulative dose of ESA (p‐for‐trend = 0.001) and a significant difference in the high annual cumulative DDD cohort (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.76–3.25; p < 0.001). The risk of genitourinary malignancy was 12.55 times higher with ESA treatment than without ESA treatment (HR, 12.55; 95% CI, 5.78–27.24; p < 0.001). ESA usage is associated with an increased risk of malignancy, particularly genitourinary cancers, in patients with CKD or ESRD. Clinicians should be aware of the occurrence of malignancy, and keep ESA dosage as low as possible. [ABSTRACT FROM AUTHOR]

Due to its advantages of high customization and rapid production, metal laser melting manufacturing (MAM) has been widely applied in the medical industry, manufacturing, aerospace and boutique industries in recent years. However, defects during the selective laser melting (SLM) manufacturing process can result from thermal stress or hardware failure during the selective laser melting (SLM) manufacturing process. To improve the product's quality, the use of defect detection during manufacturing is necessary. This study uses the process images recorded by powder bed fusion equipment to develop a detection method, which is based on the convolutional neural network. This uses three powder-spreading defect types: powder uneven, powder uncovered and recoater scratches. This study uses a two-stage convolutional neural network (CNN) model to finish the detection and segmentation of defects. The first stage uses the EfficientNet B7 to classify the images with/without defects, and then to locate the defects by evaluating three different instance segmentation networks in second stage. Experimental results show that the accuracy and Dice measurement of Mask-R-CNN network with ResNet 152 backbone can reach 0.9272 and 0.9438. The computational time of an image only takes approximately 0.2197 sec. The used CNN model meets the requirements of the early detected defects, regarding the SLM manufacturing process. [ABSTRACT FROM AUTHOR]

Foot orthotics are recommended for the treatment of hallux valgus. The effects of customized foot orthoses (FOs) designed with both medial longitudinal and transverse arch supports are poorly understood, however. This study aimed to investigate the immediate effect of customized FOs on the plantar pressure and contact area in patients with symptomatic hallux valgus. We recruited 18 patients with a mean hallux valgus angle of 27.3 ± 11.1°. Plantar pressure while walking with FOs or flat insoles (FIs) was monitored with a wireless in-shoe plantar pressure-sensing system. Peak pressure (PP), peak force (PF), pressure-time integral (PTI), force-time integral (FTI), and contact area with FOs and FIs were compared. The PF, PTI, and FTI of the midfoot were significantly higher (p < 0.05), and the PP and PTI of the rearfoot were significantly lower (p < 0.05) with the FOs than the FIs. The FOs significantly increased the contact area of the midfoot and rearfoot (p < 0.05) and reduced the contact area of the forefoot (p < 0.05). These results suggest that customized FOs redistribute plantar pressure and the contact area of the midfoot and rearfoot, improving the functional support of the midfoot for patients with hallux valgus. [ABSTRACT FROM AUTHOR]

The identification of the electromagnetic (EM) counterpart candidate ZTF19abanrhr to the binary black hole merger GW190521 opens the possibility to infer cosmological parameters from this standard siren with a uniquely identified host galaxy. The distant merger allows for cosmological inference beyond the Hubble constant. Here, we show that the three-dimensional spatial location of ZTF19abanrhr calculated from the EM data remains consistent with the latest sky localization of GW190521 provided by the LIGO-Virgo Collaboration. If ZTF19abanrhr is associated with the GW190521 merger, and assuming a flat w CDM model, we find that |$H_0=48^{+23}_{-10}\, \mathrm{km} \, \mathrm{s}^{-1}\, \mathrm{Mpc}^{-1}$|⁠ , |$\Omega _m=0.35^{+0.41}_{-0.26}$|⁠ , and |$w_0=-1.31^{+0.61}_{-0.48}$| (median and |$68{{\ \rm per\ cent}}$| credible interval). If we use the Hubble constant value inferred from another gravitational-wave event, GW170817, as a prior for our analysis, together with assumption of a flat ΛCDM and the model-independent constraint on the physical matter density ωm from Planck, we find |$H_0=68.9^{+8.7}_{-6.0}\, \mathrm{km} \, \mathrm{s}^{-1}\, \mathrm{Mpc}^{-1}$|⁠. [ABSTRACT FROM AUTHOR]

The frequency of droughts and floods is increasing due to the extreme climate. Therefore, water resource planning, allocation, and disaster prevention have become increasingly important. One of the most important kinds of hydrological data in water resources planning and management is discharge. The general way to measure the water depth and discharge is to use the Acoustic Doppler Current Profiler (ADCP), a semi-intrusive instrument. This method would involve many human resources and pose severe hazards by floods and extreme events. In recent years, it has become mainstream to measure hydrological data with nonintrusive methods such as the Large-Scale Particle Image Velocimetry (LSPIV), which is used to measure the surface velocity of rivers and estimate the discharge. However, the unknown water depth is an obstacle for this technique. In this study, a method combined with LSPIV to estimate the bathymetry was proposed. The experiments combining the LSPIV technique and the continuity equation to obtain the bed elevation were conducted in a 27 m long and 1 m wide flume. The flow conditions in the experiments were ensured to be within uniform and subcritical flow, and thermoplastic rubber particles were used as the tracking particles for the velocity measurement. The two-dimensional bathymetry was estimated from the depth-averaged velocity and the continuity equation with the leapfrog scheme in a predefined grid under the constraints of Courant–Friedrichs–Lewy (CFL). The LSPIV results were verified using Acoustic Doppler Velocimetry (ADV) measurements, and the bed elevation data of this study were verified using conventional point gauge measurements. The results indicate that the proposed method effectively estimated the variation of the bed elevation, especially in the shallow water level, with an average accuracy of 90.8%. The experimental results also showed that it is feasible to combine the nonintrusive imaging technique with the numerical calculation in solving the water depth and bed elevation. [ABSTRACT FROM AUTHOR]

The Wide-Field Infrared Transient Explorer (WINTER) is a new 1 deg2 seeing-limited time-domain survey instrument designed for dedicated near-infrared follow-up of kilonovae from binary neutron star (BNS) and neutron star–black hole mergers. WINTER will observe in the near-infrared Y, J, and short-H bands (0.9–1.7 μm, to JAB = 21 mag) on a dedicated 1 m telescope at Palomar Observatory. To date, most prompt kilonova follow-up has been in optical wavelengths; however, near-infrared emission fades more slowly and depends less on geometry and viewing angle than optical emission. We present an end-to-end simulation of a follow-up campaign during the fourth observing run (O4) of the LIGO, Virgo, and KAGRA interferometers, including simulating 625 BNS mergers, their detection in gravitational waves, low-latency and full parameter estimation skymaps, and a suite of kilonova lightcurves from two different model grids. We predict up to five new kilonovae independently discovered by WINTER during O4, given a realistic BNS merger rate. Using a larger grid of kilonova parameters, we find that kilonova emission is ≈2 times longer lived and red kilonovae are detected ≈1.5 times further in the infrared than in the optical. For 90% localization areas smaller than 150 (450) deg2, WINTER will be sensitive to more than 10% of the kilonova model grid out to 350 (200) Mpc. We develop a generalized toolkit to create an optimal BNS follow-up strategy with any electromagnetic telescope and present WINTER's observing strategy with this framework. This toolkit, all simulated gravitational-wave events, and skymaps are made available for use by the community. [ABSTRACT FROM AUTHOR]

The science objectives of the LISA mission have been defined under the implicit assumption of a 4-years continuous data stream. Based on the performance of LISA Pathfinder, it is now expected that LISA will have a duty cycle of ≈ 0.75 , which would reduce the effective span of usable data to 3 years. This paper reports the results of a study by the LISA Science Group, which was charged with assessing the additional science return of increasing the mission lifetime. We explore various observational scenarios to assess the impact of mission duration on the main science objectives of the mission. We find that the science investigations most affected by mission duration concern the search for seed black holes at cosmic dawn, as well as the study of stellar-origin black holes and of their formation channels via multi-band and multi-messenger observations. We conclude that an extension to 6 years of mission operations is recommended. [ABSTRACT FROM AUTHOR]

Purpose: To develop a novel post‐processing pipeline for hyperpolarized (HP) 13C MRSI that integrates tensor denoising and B1+ correction to measure pyruvate‐to‐lactate conversion rates (kPL) in patients with liver tumors. Methods: Seven HP 13C MR scans of progressing liver tumors were acquired using a custom 13C surface transmit/receive coil and the echo‐planar spectroscopic imaging (EPSI) data analysis included B0 correction, tensor rank truncation, and zero‐ and first‐order phase corrections to recover metabolite signals that would otherwise be obscured by spectral noise as well as a correction for inhomogeneous transmit (B1+) using a B1+ map aligned to the coil position for each patient scan. Processed HP data and corrected flip angles were analyzed with an inputless two‐site exchange model to calculate kPL. Results: Denoising averages SNR increases of pyruvate, lactate, and alanine were 37.4‐, 34.0‐, and 20.1‐fold, respectively, with lactate and alanine dynamics most noticeably recovered and better defined. In agreement with Monte Carlo simulations, over‐flipped regions underestimated kPL and under‐flipped regions overestimated kPL. B1+ correction addressed this issue. Conclusion: The new HP 13C EPSI post‐processing pipeline integrated tensor denoising and B1+ correction to measure kPL in patients with liver tumors. These technical developments not only recovered metabolite signals in voxels that did not receive the prescribed flip angle, but also increased the extent and accuracy of kPL estimations throughout the tumor and adjacent regions including normal‐appearing tissue and additional lesions. [ABSTRACT FROM AUTHOR]

Purpose: To improve hyperpolarized 13C (HP‐13C) MRI by image denoising with a new approach, patch‐based higher‐order singular value decomposition (HOSVD). Methods: The benefit of using a patch‐based HOSVD method to denoise dynamic HP‐13C MR imaging data was investigated. Image quality and the accuracy of quantitative analyses following denoising were evaluated first using simulated data of [1‐13C]pyruvate and its metabolic product, [1‐13C]lactate, and compared the results to a global HOSVD method. The patch‐based HOSVD method was then applied to healthy volunteer HP [1‐13C]pyruvate EPI studies. Voxel‐wise kinetic modeling was performed on both non‐denoised and denoised data to compare the number of voxels quantifiable based on SNR criteria and fitting error. Results: Simulation results demonstrated an 8‐fold increase in the calculated SNR of [1‐13C]pyruvate and [1‐13C]lactate with the patch‐based HOSVD denoising. The voxel‐wise quantification of kPL (pyruvate‐to‐lactate conversion rate) showed a 9‐fold decrease in standard errors for the fitted kPL after denoising. The patch‐based denoising performed superior to the global denoising in recovering kPL information. In volunteer data sets, [1‐13C]lactate and [13C]bicarbonate signals became distinguishable from noise across captured time points with over a 5‐fold apparent SNR gain. This resulted in >3‐fold increase in the number of voxels quantifiable for mapping kPB (pyruvate‐to‐bicarbonate conversion rate) and whole brain coverage for mapping kPL. Conclusions: Sensitivity enhancement provided by this denoising significantly improved quantification of metabolite dynamics and could benefit future studies by improving image quality, enabling higher spatial resolution, and facilitating the extraction of metabolic information for clinical research. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus is common in patients undergoing dialysis. However, the association between anti-diabetic drug use and survival outcomes is rarely discussed. We aimed to investigate whether continued anti-diabetic medication use affects the survival of diabetic dialysis patients and whether different hypoglycemic drug use influences prognosis. Methods: Using a nationwide database, we enrolled patients with incident end-stage renal disease under maintenance dialysis during 2011–2015 into the pre-existing diabetes dialysis (PDD), incident diabetes after dialysis (IDD), and non-diabetic dialysis (NDD) groups. The PDD group was further subclassified into patients who continued (PDD-M) and discontinued (PDD-NM) anti-diabetic drug use after dialysis. Results: A total of 5249 dialysis patients were examined. The PDD-NM group displayed a significantly higher mortality rate than the IDD, PDD-M, and NDD groups (log-rank test P < 0.001). The PDD-M group had a significantly lower risk of death, regardless of insulin (P < 0.001) or oral hypoglycemic agent (OHA) (P < 0.001) use. Initial insulin administration or OHA had no statistically significant effect on overall mortality in the IDD group. But OHA use had better survival trends than insulin administration for the older (P = 0.02) and male subgroups (P = 0.05). Conclusions: For dialysis patients with diabetes, continuous administration of anti-diabetic drugs after dialysis and choice of medication may affect outcomes. [ABSTRACT FROM AUTHOR]

User-item interactions in social media provide a rich dataset for wide applications such as viral marketing and recommender systems. Post retweeting behaviors and venue check-in events by users are the most representative. While existing studies predict items' rise and fall, i.e., tweet popularity and venue closure detection, using hand-crafted features, this paper aims at exploring feature representation learning to improve prediction performance. We target at two essential time-series classification tasks on social media, including Shutdown Risk Prediction (SRP) of venues and Tweet Popularity Prediction (TPP) of posts. We study how feature representation learning of items can benefit both SRP and TPP tasks. The main idea is to learn item embedding vectors as features in item-item graphs constructed from time series of check-in events and retweeting behaviors. The learned features are used together with manually-defined features to enlarge the representation capability. In the TPP task, we also propose a pattern-aware self-exciting point process (PSEISMIC) model to generate time-series features. Experiments conducted on Instagram, Foursquare, and Twitter datasets exhibit promising performance of jointly utilizing learned and extracted features in both tasks. PSEISMIC can also further boost TPP accuracy. The major contribution of this work is three-fold. First, we propose to jointly deal with SRP and TPP under the same framework of feature extraction and learning. Second, we show that feature presentation learning of items can benefit these two prediction tasks with time series data. Third, by incorporating time series patterns, the proposed PSEISMIC further improves the performance of popularity prediction. [ABSTRACT FROM AUTHOR]

Abstract Based on the expanding set of applications for hyperpolarized carbon‐13 (HP‐13C) MRI, this work aims to communicate standardized methodology implemented at the University of California, San Francisco, as a primer for conducting reproducible metabolic imaging studies of the prostate and brain. Current state‐of‐the‐art HP‐13C acquisition, data processing/reconstruction and kinetic modeling approaches utilized in patient studies are presented together with the rationale underpinning their usage. Organized around spectroscopic and imaging‐based methods, this guide provides an extensible framework for handling a variety of HP‐13C applications, which derives from two examples with dynamic acquisitions: 3D echo‐planar spectroscopic imaging of the human prostate and frequency‐specific 2D multislice echo‐planar imaging of the human brain. Details of sequence‐specific parameters and processing techniques contained in these examples should enable investigators to effectively tailor studies around individual‐use cases. Given the importance of clinical integration in improving the utility of HP exams, practical aspects of standardizing data formats for reconstruction, analysis and visualization are also addressed alongside open‐source software packages that enhance institutional interoperability and validation of methodology. To facilitate the adoption and further development of this methodology, example datasets and analysis pipelines have been made available in the supporting information. [ABSTRACT FROM AUTHOR]

The emergence of carbapenem-resistant Enterobacterales (CRE) has become a major public health concern. Moreover, its colonization among residents of long-term care facilities (LTCFs) is associated with subsequent infections and mortality. To further explore the various aspects concerning CRE in LTCFs, we conducted a literature review on CRE colonization and/or infections in long-term care facilities. The prevalence and incidence of CRE acquisition among residents of LTCFs, especially in California, central Italy, Spain, Japan, and Taiwan, were determined. There was a significant predominance of CRE in LTCFs, especially in high-acuity LTCFs with mechanical ventilation, and thus may serve as outbreak centers. The prevalence rate of CRE in LTCFs was significantly higher than that in acute care settings and the community, which indicated that LTCFs are a vital reservoir for CRE. The detailed species and genomic analyses of CRE among LTCFs reported that Klebsiella pneumoniae is the primary species in the LTCFs in the United States, Spain, and Taiwan. KPC-2-containing K. pneumoniae strains with sequence type 258 is the most common sequence type of KPC-producing K. pneumoniae in the LTCFs in the United States. IMP-11- and IMP-6-producing CRE were commonly reported among LTCFs in Japan. OXA-48 was the predominant carbapenemase among LTCFs in Spain. Multiple risk factors associated with the increased risk for CRE acquisition in LTCFs were found, such as comorbidities, immunosuppressive status, dependent functional status, usage of gastrointestinal devices or indwelling catheters, mechanical ventilation, prior antibiotic exposures, and previous culture reports. A high CRE acquisition rate and prolonged CRE carriage duration after colonization were found among residents in LTCFs. Moreover, the patients from LTCFs who were colonized or infected with CRE had poor clinical outcomes, with a mortality rate of up to 75% in infected patients. Infection prevention and control measures to reduce CRE in LTCFs is important, and could possibly be controlled via active surveillance, contact precautions, cohort staffing, daily chlorhexidine bathing, healthcare-worker education, and hand-hygiene adherence. [ABSTRACT FROM AUTHOR]

Background and Objective: Systematic reviews and meta-analyses of direct oral anticoagulants (DOACs) for patients with chronic kidney disease (CKD) or dialysis patients are lacking. We aimed to compare the efficacy and safety of DOACs and warfarin in patients with CKD requiring anticoagulation therapy. Methods: We performed a systematic review and meta-analysis of six randomized controlled trials and 19 observational studies, with the inclusion criteria being a comparative study between DOACs and warfarin in patients with CKD or dialysis patients from database inception until August 2020. The efficacy outcomes were stroke, systemic embolism (SE), or venous thromboembolism (VTE), and the safety outcome was major bleeding. Results: Compared with warfarin, DOACs significantly reduced the risk of stroke/SE/VTE by 22% (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64–0.95) and major bleeding by 17% (HR = 0.83, 95% CI 0.71–0.97). On comparing factor Xa inhibitors and dabigatran with warfarin separately, factor Xa inhibitors significantly reduced the risk of stroke/SE/VTE (HR = 0.78, 95% CI 0.62–0.98) and major bleeding (HR = 0.76, 95% CI 0.64–0.91) overall in patients. Comparing each DOACs with warfarin separately, apixaban was associated with a significantly better risk reduction of stroke/SE/VTE (25% risk reduction) and major bleeding (35% risk reduction) than warfarin. Compared with warfarin, DOACs significantly reduced the risk of stroke, SE, or VTE by 19% (HR = 0.81, 95% CI 0.68–0.97) in patients with CKD stage 3 and significantly lowered the risk of major bleeding by 31% (HR = 0.69, 95% CI 0.56–0.85) in patients with CKD stages 4–5. Conclusions: In pooled, analyzed randomized controlled trials and observational studies, DOACs were associated with better efficacy in early CKD, as well as similar efficacy and safety outcomes to warfarin in patients with CKD stages 4–5 or dialysis patients. The results of patients with CKD stages 4–5 and dialysis patients were from observational studies. Well-designed randomized controlled trials focused on DOAC use in patients with CKD and dialysis patients are needed. PROSPERO register number: CRD42020150599, 6 February, 2020. [ABSTRACT FROM AUTHOR]

We present quantities which characterize the sensitivity of gravitational-wave observatories to sources at cosmological distances. In particular, we introduce and generalize the horizon, range, response, and reach distances. These quantities incorporate a number of important effects, including cosmologically well-defined distances and volumes, cosmological redshift, cosmological time dilation, and rate density evolution. In addition, these quantities incorporate unique aspects of gravitational wave detectors, such as the variable sky sensitivity of the detectors and the scaling of the sensitivity with inverse distance. An online calculator (https://users.rcc.uchicago.edu/~dholz/gwc/) and python notebook (https://github.com/hsinyuc/distancetool) to determine GW distances are available. We provide answers to the question: 'How far can gravitational-wave detectors hear?' [ABSTRACT FROM AUTHOR]

MRI with hyperpolarized carbon‐13 agents has created a new type of noninvasive, in vivo metabolic imaging that can be applied in cell, animal, and human studies. The use of 13C‐labeled agents, primarily [1‐13C]pyruvate, enables monitoring of key metabolic pathways with the ability to image substrate and products based on their chemical shift. Over 10 sites worldwide are now performing human studies with this new approach for studies of cancer, heart disease, liver disease, and kidney disease. Hyperpolarized metabolic imaging studies must be performed within several minutes following creation of the hyperpolarized agent due to irreversible decay of the net magnetization back to equilibrium, so fast imaging methods are critical. The imaging methods must include multiple metabolites, separated based on their chemical shift, which are also undergoing rapid metabolic conversion (via label exchange), further exacerbating the challenges of fast imaging. This review describes the state‐of‐the‐art in fast imaging methods for hyperpolarized metabolic imaging. This includes the approach and tradeoffs between three major categories of fast imaging methods—fast spectroscopic imaging, model‐based strategies, and metabolite specific imaging—as well additional options of parallel imaging, compressed sensing, tailored RF flip angles, refocused imaging methods, and calibration methods that can improve the scan coverage, speed, signal‐to‐noise ratio (SNR), resolution, and/or robustness of these studies. To date, these approaches have produced extremely promising initial human imaging results. Improvements to fast hyperpolarized metabolic imaging methods will provide better coverage, SNR, resolution, and reproducibility for future human imaging studies. Level of Evidence: 5 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

Background: Early detection and treatment of Gram-negative bacteria (GNB), major causative pathogens of sepsis (a potentially fatal condition caused by the body's response to an infection), may benefit a patient's outcome, since the mortality rate increases by 5-10% for each hour of delayed therapy. Unfortunately, GNB diagnosis is based on bacterial culture, which is time consuming. Therefore, an economic and effective GNB (defined as a positive blood, sputum, or urine culture) infection detection tool in the emergency department (ED) is warranted.Methods: We conducted a retrospective cohort study in the ED of a university-affiliated medical center between January 01, 2014 and December 31, 2017. The inclusion criteria were as follows: (1) age ≥ 18; (2) clinical suspicion of bacterial infection; (3) bacterial culture from blood, sputum, or urine ordered and obtained in the ED. Descriptive statistics was performed on patient demographic characteristics, vital signs, laboratory data, infection sites, cultured microorganisms, and clinical outcomes. The accuracy of vital signs to predict GNB infection was identified via univariate logistic regression and receiver operating characteristic (ROC) curve analysis.Results: A total of 797 patients were included in this study; the mean age was 71.8 years and 51.3% were male. The odds ratios of patients with body temperature ≥ 38.5 °C, heart rate ≥ 110 beats per minute, respiratory rate ≥ 20 breaths per minute, and Glasgow coma scale (GCS) < 14, in predicting GNB infection were found to be 2.3, 1.4, 1.9, and 1.6, respectively. The area under the curve values for ROC analysis of these measures were 0.70, 0.68, 0.69, and 0.67, respectively.Conclusion: The four physiological parameters were rapid and reliable independent predictors for detection of GNB infection. [ABSTRACT FROM AUTHOR]

Purpose: With the initiation of human hyperpolarized 13C (HP‐13C) trials at multiple sites and the development of improved acquisition methods, there is an imminent need to maximally extract diagnostic information to facilitate clinical interpretation. This study aims to improve human HP‐13C MR spectroscopic imaging through means of Tensor Rank truncation‐Image enhancement (TRI) and optimal receiver combination (ORC). Methods: A data‐driven processing framework for dynamic HP 13C MR spectroscopic imaging (MRSI) was developed. Using patient data sets acquired with both multichannel arrays and single‐element receivers from the brain, abdomen, and pelvis, we examined the theory and application of TRI, as well as 2 ORC techniques: whitened singular value decomposition (WSVD) and first‐point phasing. Optimal conditions for TRI were derived based on bias‐variance trade‐off. Results: TRI and ORC techniques together provided a 63‐fold mean apparent signal‐to‐noise ratio (aSNR) gain for receiver arrays and a 31‐fold gain for single‐element configurations, which particularly improved quantification of the lower‐SNR‐[13C]bicarbonate and [1‐13C]alanine signals that were otherwise not detectable in many cases. Substantial SNR enhancements were observed for data sets that were acquired even with suboptimal experimental conditions, including delayed (114 s) injection (8× aSNR gain solely by TRI), or from challenging anatomy or geometry, as in the case of a pediatric patient with brainstem tumor (597× using combined TRI and WSVD). Improved correlation between elevated pyruvate‐to‐lactate conversion, biopsy‐confirmed cancer, and mp‐MRI lesions demonstrated that TRI recovered quantitative diagnostic information. Conclusion: Overall, this combined approach was effective across imaging targets and receiver configurations and could greatly benefit ongoing and future HP 13C MRI research through major aSNR improvements. [ABSTRACT FROM AUTHOR]

Cephalic arch stenosis (CAS) is a common cause of AV dialysis access failure and is notoriously difficult to treat with conventional venoplasty. Although stent graft (SG) placement has improved patency rate, they are prone to stent failure caused by edge stenosis. We investigate the effect of SG diameter relative to cephalic vein on patency rate among hemodialysis patients with dysfunctional arteriovenous access caused by CAS. We identified 22 patients with recalcitrant cephalic arch stenosis or post-venoplasty vessel rupture and received SG placement. Patients were divided into two groups based on the stent-to-vessel diameter (S/V) ratio: undersized group, < 1; and apposed group, 1–1.2. Outcomes were assessed through follow-up angiography. S/V ratio was significant smaller in the undersized patient group (p < 0.001). Placement of undersized SG demonstrated higher primary stent (p = 0.001) and access patency rates (p = 0.021) and a reduced number of post-treatment reinterventions per access year (p = 0.021). A decreased number of lateral edge stenosis was noted in undersized SG (p = 0.005). Increased S/V ratio was significantly associated with lateral edge stenosis (OR = 5.19; p = 0.027). Undersized SG is associated with higher primary stent and access patency rate, and decreased number of post-SG interventions, and are suggested in the treatment of cephalic arch stenosis. [ABSTRACT FROM AUTHOR]