Deep learning based linear energy transfer calculation for proton therapy.

Objective.This study aims to address the limitations of traditional methods for calculating linear energy transfer (LET), a critical component in assessing relative biological effectiveness (RBE). Currently, Monte Carlo (MC) simulation, the gold-standard for accuracy, is resource-intensive and slow for dose optimization, while the speedier analytical approximation has compromised accuracy. Our objective was to prototype a deep-learning-based model for calculating dose-averaged LET (LETd) using patient anatomy and dose-to-water (DW) data, facilitating real-time biological dose evaluation and LET optimization within proton treatment planning systems.Approach. 275 4-field prostate proton Stereotactic Body Radiotherapy plans were analyzed, rendering a total of 1100 fields. Those were randomly split into 880, 110, and 110 fields for training, validation, and testing. A 3D Cascaded UNet model, along with data processing and inference pipelines, was developed to generate patient-specific LETddistributions from CT images and DW. The accuracy of the LETdof the test dataset was evaluated against MC-generated ground truth through voxel-based mean absolute error (MAE) and gamma analysis.Main results.The proposed model accurately inferred LETddistributions for each proton field in the test dataset. A single-field LETdcalculation took around 100 ms with trained models running on a NVidia A100 GPU. The selected model yielded an average MAE of 0.94 ± 0.14 MeV cm-1and a gamma passing rate of 97.4% ± 1.3% when applied to the test dataset, with the largest discrepancy at the edge of fields where the dose gradient was the largest and counting statistics was the lowest.Significance.This study demonstrates that deep-learning-based models can efficiently calculate LETdwith high accuracy as a fast-forward approach. The model shows great potential to be utilized for optimizing the RBE of proton treatment plans. Future efforts will focus on enhancing the model's performance and evaluating its adaptability to different clinical scenarios.

Proton versus photon craniospinal irradiation for adult medulloblastoma: A dosimetric, toxicity, and exploratory cost analysis.

Background: This study aimed to determine whether proton craniospinal irradiation (CSI) decreased the dose to normal tissue and resulted in less toxicity than photon CSI for adult patients. Methods: This single-institution retrospective analyzed differences in radiation doses, acute toxicity, and cost between proton and CSI for adult medulloblastoma patients. Results: Of 39 total patients, 20 were treated with photon CSI prior to 2015, and 19 were treated with proton CSI thereafter. Median age was 28 years (range 18-66). The molecular subtype was most commonly sonic hedgehog (68%). Patients most commonly received 36 Gy CSI in 20 fractions with a boost to 54-55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to cochleae, lacrimal glands, lens, parotid glands, pharyngeal constrictors, esophagus, lungs, liver, and skin (all P < .001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% versus 35%, P = .044) and decreased median weight loss during radiation (+1.0 versus -2.8 kg, P = .011). Weight loss was associated with acute hospitalization (P = .009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At the last follow-up, 5 photon patients had died (2 of progressive disease, 3 without recurrence ages 41-63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free. Conclusions: This study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment.

Comprehensive assessment of resources for prevention and control of chronic and non-communicable diseases in China: a cross-sectional study.

OBJECTIVE: This study aims to comprehensively evaluate the resources for prevention and control of chronic and non-communicable diseases (NCDs) in China to provide a reference basis for optimising the resource allocation for prevention and control of NCDs. METHODS: China Chronic Disease and Risk Factor Surveillance sites and National Demonstration Areas for Integrated Chronic and Non-communicable Disease Prevention and Control (NCDDA) were selected as investigation objects. In December 2021, the district (or county) resource allocation for NCD prevention and control was investigated through the NCDDA management information system. According to the index system of NCD prevention and control, 31 indicators of 6 dimensions were collected, and the weighted technique for order preference by similarity to an ideal solution, weighted rank-sum ratio and fuzzy comprehensive evaluation methods were used for comprehensive evaluation of resources for prevention and control of NCDs. RESULTS: The 653 districts (or counties) in this study cover 22.96% of China's districts (or counties). The top three weights were full-time staff for NCD prevention and control (0.1066), the amount of funds for NCD prevention and control (0.0967), and the coverage rate of districts (or counties) establishing chronic obstructive pulmonary disease surveillance information system (0.0886). The comprehensive evaluation results for the resources for prevention and control of NCDs by the three methods were basically the same. The results of fuzzy comprehensive evaluation showed that the resource allocation in urban areas (0.9268) was better than that in rural areas (0.3257), the one in eastern region (0.9016) was better than that in central (0.3844) and western regions (0.3868), and the one in NCDDA (0.9625) was better than that in non-NCDDA (0.2901). CONCLUSION: The resources in China for NCD prevention and control differ among different regions, which should be taken into account in future policymaking and resource allocation.

Differences in Insurance Coverage for Individuals With Schizophrenia After Implementation of the Patient Protection and Affordable Care Act.

This cross-sectional study uses Medical Expenditure Panel Survey data to assess differences in insurance coverage for individuals with schizophrenia before vs after implementation of the Patient Protection and Affordable Care Act (ACA).

Clinical Benefit of Therapeutic Drug Monitoring in Colorectal Cancer Patients Who Received Fluorouracil-Based Chemotherapy.

BACKGROUND The impact of therapeutic drug management (TDM) on reducing toxicity and improving efficacy in colorectal cancer (CRC) patients receiving fluorouracil-based chemotherapy is still unclear. MATERIAL AND METHODS A total of 207 patients (Study Group n=54, Historical Group n=153) with metastatic colorectal cancer were enrolled. All of them received 6 administrations of the 5-FU based regimens. Initial 5-FU dosing of all patients was calculated using body surface area (BSA). In the Study Group, individual exposure during each cycle was measured using a nanoparticle immunoassay, and the 5-FU blood concentration was calculated using the area under the curve (AUC). We adjusted the 5-FU infusion dose of the next cycle based on the AUC data of the previous cycle to achieve the target of 20-30 mg×h/L. RESULTS In the fourth cycle, patients in the target concentration range (AUC mean, 26.3 mg×h/L; Median, 28 mg×h/L; Range, 14-38 mg×h/L; CV, 22.4%) accounted for 46.8% of all patients, which were more than the ones in the first cycle (P<0.001). 5-FU TDM significantly reduced the toxicity of chemotherapy and improved its efficacy. The Study Group (30/289) showed a lower percentage of severe adverse events than that in the Historical Group (185/447) (P<0.001). The incidences of complete response and partial response in the Study Group were higher than those in the Historical Group (P=0.032). CONCLUSIONS TDM in colorectal cancer can reduce toxicity, improve efficacy and clinical outcome, and can be routinely used in 5-FU-based chemotherapy.

Multifunctional Near-Infrared Fluorescent Probes with Different Ring-Structure Trigger Groups for Cell Health Monitoring and In Vivo Esterase Activity Detection.

A series of multifunctional ratiometric near-infrared fluorescent probes (CYOH-3, CYOH-4, CYOH-5, and CYOH-6) for esterase detection are designed by gradually changing the deflection of the plane twist in the molecule. These probes are composed of different ring-structure trigger groups (from three-membered ring to six-membered ring) and the same luminescent group CYOH. These probes show maximum absorption at ∼585 nm and a fluorescence emission peak at ∼655 ± 5 nm. In the presence of esterase, the probes were hydrolyzed to expose the fluorophore CYOH (λabs = 690 nm, λem = 710 ± 5 nm), thus exhibiting ratiometric near-infrared fluorescence. The probe CYOH-6 has lower plane deflection angle and better ratiometric (R = I710±5nm/I657±4nm) fluorescence properties than probes CYOH-3, CYOH-4, and CYOH-5. CYOH-6 (six-membered ring) has been successfully used to target esterase in mitochondria and distinguish between dead cells (esterase inactivation) and live cells. In addition, CYOH-6 has been well used for monitoring of esterase activity in zebrafish and mice, which proves that these probes have good prospects for clinical biomedical applications.

Porous Gold Nanocages: High Atom Utilization for Thiolated Aptamer Immobilization to Well Balance the Simplicity, Sensitivity, and Cost of Disposable Aptasensors.

Gold nanostructures such as nanospheres, nanorods, or nanowires have been extensively used for electrode surface modification because they not only can increase the overall electroactive surface but can also provide anchoring sites for thiolated aptamers through facile Au-S covalent bonds. However, all of those gold nanostructures used are solid and only the outer surface is attractive. In the aim to reduce the usage of precious gold, in this paper, porous gold nanocages (AuNCs) with both inner and outer walls for effective aptamer immobilization have been electrostatically adhered on a screen-printed carbon electrode (SPCE), to develop a highly sensitive aptasensor in a truly label-free manner. Specifically, the thiolated aptamers specific for aflatoxin B1 (AFB1) were chosen as the model aptamer and covalently bound to the inner and outer surface of AuNCs using Au-S chemistry. Exposing the sensing interface to targets could initiate the formation of the aptamer/target complex, resulting in an increased interfacial electron transfer resistance on the SPCE. Under optimal conditions, this aptasensor could detect AFB1 in a wide range of 0.1 pg mL-1 to 100 ng mL-1 with a high linear fit and has an ultralow detection limit of 0.03 pg mL-1 (S/N = 3). The developed aptasensor has remarkable merits such as simpler operation, more cost-effective, more sensitive, and less reagent consumption. We therefore provided a universal strategy to well balance the simplicity, sensitivity, and cost of disposable aptasensors for a large population of targets having specific aptamer strands.

Leaders' Expressed Humility and Followers' Feedback Seeking: The Mediating Effects of Perceived Image Cost and Moderating Effects of Power Distance Orientation.

We developed and tested a model to identify the role of leaders' expressed humility on employees' feedback-seeking processes. The data used in our study was from a sample of 248 employees and 57 of their immediate supervisors. The results revealed that: (1) leader's expressed humility positively related to employees' feedback seeking mediated by employees' perceived image cost; and (2) power distance orientation moderated the relationship between leader's expressed humility and employees' perceived image costs, such that the relationship was stronger when the power distance orientation was lower rather than higher. The results offer new insight into potential managerial practices that aim at stimulating feedback seeking. We conclude with a discussion for future research.

Spectral Similarity Assessment Based on a Spectrum Reflectance-Absorption Index and Simplified Curve Patterns for Hyperspectral Remote Sensing.

Hyperspectral images possess properties such as rich spectral information, narrow bandwidth, and large numbers of bands. Finding effective methods to retrieve land features from an image by using similarity assessment indices with specific spectral characteristics is an important research question. This paper reports a novel hyperspectral image similarity assessment index based on spectral curve patterns and a reflection-absorption index. First, some spectral reflection-absorption features are extracted to restrict the subsequent curve simplification. Then, the improved Douglas-Peucker algorithm is employed to simplify all spectral curves without setting the thresholds. Finally, the simplified curves with the feature points are matched, and the similarities among the spectral curves are calculated using the matched points. The Airborne Visible Infrared Imaging Spectrometer (AVIRIS) and Reflective Optics System Imaging Spectrometer (ROSIS) hyperspectral image datasets are then selected to test the effect of the proposed index. The practical experiments indicate that the proposed index can achieve higher precision and fewer points than the traditional spectral information divergence and spectral angle match.

[Impact of Phosphogypsum Wastes on the Wheat Growth and CO2 Emissions and Evaluation of Economic-environmental Benefit].

Phosphogypsum is a phosphorus chemical waste which has not been managed and reused well, resultantly, causing environmental pollution and land-occupation. Phosphogypsum wastes were used as a soil amendment to assess the effect on wheat growth, yield and CO2 emissions from winter wheat fields. Its economic and environmental benefits were analyzed at the same time. The results showed that wheat yield was increased by 37.71% in the treatment of phosphogypsum of 2 100 kg x hm(-2). Compared with the control treatment, throughout the wheat growing season, CO2 emission was accumulatively reduced by 3% in the treatment of phosphogypsum waste of 1050 kg x hm(-2), while reduced by 8% , 10% , and 6% during the jointing stage, heading date and filling period of wheat, respectively; while CO2 emission was accumulatively reduced by 7% in the treatment of phosphogypsum waste of 2 100 kg x hm(-2) throughout the wheat growing season, as reduced by 11% , 4% , and 12% during the reviving wintering stage, heading date and filling period of wheat, respectively. It was better for CO2 emission reduction in the treatment of a larger amount of phosphogypsum waste. In the case of application of phosphogypsum waste residue within a certain range, the emission intensity of CO2 ( CO2 emissions of per unit of fresh weight or CO2 emissions of per unit of yield) , spike length, fresh weight and yield showed a significantly negative correlation--the longer the ear length, the greater fresh weight and yield and the lower the CO2 emissions intensity. As to the carbon trading, phosphogypsum utilization was of high economic and environmental benefits. Compared with the control, the ratio of input to output changed from 1: 8.3 to 1: 10.7, which in the same situation of investment the output could be increased by 28.92% ; phosphogypsum as a greenhouse gas reducing agent in the wheat field, it could decrease the cost and increase the environmental benefit totally about 290 yuan per unit of ton. The results demonstrated phosphogypsum wastes could obviously decrease the CO2 emission from field soil and had a great potential to control agricultural greenhouse gases. Hopefully it has an important application perspective for the low-carbon, ecological and sustainable agricultural development.

Epidemiology and Clinical Correlates of AKI in Chinese Hospitalized Adults.

BACKGROUND AND OBJECTIVES: Comprehensive epidemiologic data on AKI are particularly lacking in Asian countries. This study sought to assess the epidemiology and clinical correlates of AKI among hospitalized adults in China. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a multicenter retrospective cohort study of 659,945 hospitalized adults from a wide range of clinical settings in nine regional central hospitals across China in 2013. AKI was defined and staged according to Kidney Disease Improving Global Outcomes criteria. The incidence of AKI in the cohort was estimated using a novel two-step approach with adjustment for the frequency of serum creatinine tests and other potential confounders. Risk factor profiles for hospital-acquired (HA) and community-acquired (CA) AKI were examined. The in-hospital outcomes of AKI, including mortality, renal recovery, length of stay, and daily cost, were assessed. RESULTS: The incidence of CA-AKI and HA-AKI was 2.5% and 9.1%, respectively, giving rise to an overall incidence of 11.6%. Although the risk profiles for CA-AKI and HA-AKI differed, preexisting CKD was a major risk factor for both, contributing to 20% of risk in CA-AKI and 12% of risk in HA-AKI. About 40% of AKI cases were possibly drug-related and 16% may have been induced by Chinese traditional medicines or remedies. The in-hospital mortality of AKI was 8.8%. The risk of in-hospital death was higher among patients with more severe AKI. Preexisting CKD and need for intensive care unit admission were associated with higher death risk in patients at any stage of AKI. Transiency of AKI did not modify the risk of in-hospital death. AKI was associated with longer length of stay and higher daily costs, even after adjustment for confounders. CONCLUSION: AKI is common in hospitalized adults in China and is associated with significantly higher in-hospital mortality and resource utilization.

A facile label-free colorimetric aptasensor for acetamiprid based on the peroxidase-like activity of hemin-functionalized reduced graphene oxide.

A facile aptasensor has been developed for the colorimetric detection of acetamiprid by using the hemin-functionalized reduced graphene oxide (hemin-rGO) composites. The as-prepared hemin-rGO composites possessed both the ability of rGO to physically adsorb the aptamers and the peroxidase-like activity of hemin that could catalyse 3,3,5,5-tetramethylbenzidine (TMB) in the presence of H2O2, to produce a solution with blue color. The well-dispersed hemin-rGO composites coagulated completely at the proper salt concentration; however, the coagulation of hemin-rGO was vanished when abundant aptamers were adsorbed on its surface because the attached negatively charged DNA backbone increased individual hemin-rGO electrostatic repulsion. In the detection scheme, acetamiprid with different concentrations was firstly incubated with the same amount of aptamer. The more acetamiprid in the tested solution, the less free aptamers were absorbed on the hemin-rGO surface, making the composites coagulate to a higher degree in the presence of the optimum NaCl concentration. As a consequence, the content of hemin-rGO in the supernatant was decreased after centrifugation, which catalysed oxidation of TMB in the presence of H2O2 to produce light blue color with a low absorbance. The color variation relavant to the acetamiprid concentration can be judged by the naked eyes and easily monitored by the inexpensive UV-vis spectrometer. Such designed aptasensor displayed a linear response for acetamiprid in the range from 100nM to 10µM with a detection limit of 40nM (S/N=3). This colorimetric aptasensing platform offers great advantages including the simple operation process, low-cost portable instrument, and user-friendly applications.

The US healthcare workforce and the labor market effect on healthcare spending and health outcomes.

The healthcare sector was one of the few sectors of the US economy that created new positions in spite of the recent economic downturn. Economic contractions are associated with worsening morbidity and mortality, declining private health insurance coverage, and budgetary pressure on public health programs. This study examines the causes of healthcare employment growth and workforce composition in the US and evaluates the labor market's impact on healthcare spending and health outcomes. Data are collected for 50 states and the District of Columbia from 1999-2009. Labor market and healthcare workforce data are obtained from the Bureau of Labor Statistics. Mortality and health status data are collected from the Centers for Disease Control and Prevention's Vital Statistics program and Behavioral Risk Factor Surveillance System. Healthcare spending data are derived from the Centers for Medicare and Medicaid Services. Dynamic panel data regression models, with instrumental variables, are used to examine the effect of the labor market on healthcare spending, morbidity, and mortality. Regression analysis is also performed to model the effects of healthcare spending on the healthcare workforce composition. All statistical tests are based on a two-sided [Formula: see text] significance of [Formula: see text] .05. Analyses are performed with STATA and SAS. The labor force participation rate shows a more robust effect on healthcare spending, morbidity, and mortality than the unemployment rate. Study results also show that declining labor force participation negatively impacts overall health status ([Formula: see text] .01), and mortality for males ([Formula: see text] .05) and females ([Formula: see text] .001), aged 16-64. Further, the Medicaid and Medicare spending share increases as labor force participation declines ([Formula: see text] .001); whereas, the private healthcare spending share decreases ([Formula: see text] .001). Public and private healthcare spending also has a differing effect on healthcare occupational employment per 100,000 people. Private healthcare spending positively impacts primary care physician employment ([Formula: see text] .001); whereas, Medicare spending drives up employment of physician assistants, registered nurses, and personal care attendants ([Formula: see text] .001). Medicaid and Medicare spending has a negative effect on surgeon employment ([Formula: see text] .05); the effect of private healthcare spending is positive but not statistically significant. Labor force participation, as opposed to unemployment, is a better proxy for measuring the effect of the economic environment on healthcare spending and health outcomes. Further, during economic contractions, Medicaid and Medicare's share of overall healthcare spending increases with meaningful effects on the configuration of state healthcare workforces and subsequently, provision of care for populations at-risk for worsening morbidity and mortality.

Neural mechanisms underlying the cost of task switching: an ERP study.

BACKGROUND: When switching from one task to a new one, reaction times are prolonged. This phenomenon is called switch cost (SC). Researchers have recently used several kinds of task-switching paradigms to uncover neural mechanisms underlying the SC. Task-set reconfiguration and passive dissipation of a previously relevant task-set have been reported to contribute to the cost of task switching. METHODOLOGY/PRINCIPAL FINDINGS: An unpredictable cued task-switching paradigm was used, during which subjects were instructed to switch between a color and an orientation discrimination task. Electroencephalography (EEG) and behavioral measures were recorded in 14 subjects. Response-stimulus interval (RSI) and cue-stimulus interval (CSI) were manipulated with short and long intervals, respectively. Switch trials delayed reaction times (RTs) and increased error rates compared with repeat trials. The SC of RTs was smaller in the long CSI condition. For cue-locked waveforms, switch trials generated a larger parietal positive event-related potential (ERP), and a larger slow parietal positivity compared with repeat trials in the short and long CSI condition. Neural SC of cue-related ERP positivity was smaller in the long RSI condition. For stimulus-locked waveforms, a larger switch-related central negative ERP component was observed, and the neural SC of the ERP negativity was smaller in the long CSI. Results of standardized low resolution electromagnetic tomography (sLORETA) for both ERP positivity and negativity showed that switch trials evoked larger activation than repeat trials in dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC). CONCLUSIONS/SIGNIFICANCE: The results provide evidence that both RSI and CSI modulate the neural activities in the process of task-switching, but that these have a differential role during task-set reconfiguration and passive dissipation of a previously relevant task-set.

SELDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of a boosting decision tree model for diagnosis of pancreatic cancer.

AIM: New technologies for the early detection of pancreatic cancer (PC) are urgently needed. The aim of the present study was to screen for the potential protein biomarkers in serum using proteomic fingerprint technology. METHODS: Magnetic beads combined with surface-enhanced laser desorption/ionization (SELDI) TOF MS were used to profile and compare the protein spectra of serum samples from 85 patients with pancreatic cancer, 50 patients with acute-on-chronic pancreatitis and 98 healthy blood donors. Proteomic patterns associated with pancreatic cancer were identified with Biomarker Patterns Software. RESULTS: A total of 37 differential m/z peaks were identified that were related to PC (P<0.01). A tree model of biomarkers was constructed with the software based on the three biomarkers (7762 Da, 8560 Da, 11654 Da), this showing excellent separation between pancreatic cancer and non-cancer., with a sensitivity of 93.3% and a specificity of 95.6%. Blind test data showed a sensitivity of 88% and a specificity of 91.4%. CONCLUSIONS: The results suggested that serum biomarkers for pancreatic cancer can be detected using SELDI-TOF-MS combined with magnetic beads. Application of combined biomarkers may provide a powerful and reliable diagnostic method for pancreatic cancer with a high sensitivity and specificity.