Development and Initial Evaluation of a Cost-Effective Force Sensor for Ureteroscopic Application.

Purpose: Retrograde intrarenal surgery is the gold-standard treatment for most kidney stones. During ureteroscopy, ureteral access sheath insertion at forces greater than 8.0 Newtons (N) risks high-grade ureteral injury. To monitor force, our institution utilizes a unique, Bluetooth-equipped device (i.e., the University of California-Irvine Force Sensor). Given the unique nature of the force sensor, we sought to develop an inexpensive and accessible force sensor based on Boyle's law and the specific amount of force required to compress an occluded 1.0 mL syringe. Materials and Methods: We evaluated three brands of 1.0 mL syringes. After setting the plunger at 1.0 mL, the syringe was occluded, and the syringe plunger was compressed. The syringe volume was recorded when the applied force on the plunger reached 4.0 N, 6.0 N, and 8.0 N. Multiple trials were performed to assess reliability and reproducibility. A method for applying this clinically was also developed. Results: The precise force thresholds identified for a 1.0 mL Luer-Lok™ Syringe (Becton Dickinson, Franklin Lakes, NJ) were 0.30 mL for 4.00 N, 0.20 mL for 6.00 N, and 0.15 mL for 8.00 N. The 1.0 mL Tuberculin Syringe and 1.0 mL Luer Slip Syringe were less precise, but compression from 1.0 to 0.40 mL, 0.25 mL, and 0.20 mL corresponded to force sensor readings that did not exceed 4.00 N, 6.00 N, and 8.00 N, respectively. Conclusions: Based on volume changes, 4.00 N, 6.00 N, and 8.00 N of force can be reliably and reproducibly achieved using an occluded 1.0 mL syringe.

In vivo assessment of dual-function submicron textured nitric oxide releasing catheters in a 7-day rabbit model.

Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. Herein, a dualfunction submicron textured nitric oxide (NO)-releasing catheter was developed. The hemocompatibility and antithrombotic activity of vascular catheters were evaluated in both 20 h in vitro blood loop and 7 d in vivo rabbit model. Surface characterization assessments via atomic force microscopy show the durability of the submicron pattern after incorporation of NO donor S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-doped catheters exhibited prolonged and controlled NO release mimicking the levels released by endothelium. Fabricated catheters showed cytocompatibility when evaluated against BJ human fibroblast cell lines. After 20h in vitro evaluation of catheters in a blood loop, textured-NO catheters exhibited a 13-times reduction in surface thrombus formation compared to the control catheters, which had 83% of the total area covered by clots. After the 7 d in vivo rabbit model, analysis on the catheter surface was examined via scanning electron microscopy, where significant reduction of platelet adhesion, fibrin mesh, and thrombi can be observed on the NO-releasing textured surfaces. Moreover, compared to relative controls, a 63% reduction in the degree of thrombus formation within the jugular vein was observed. Decreased levels of fibrotic tissue decomposition on the jugular vein and reduced platelet adhesion and thrombus formation on the texture of the NO-releasing catheter surface are indications of mitigated foreign body response. This study demonstrated a biocompatible and robust dual-functioning textured NO PU catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. STATEMENT OF SIGNIFICANCE: Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. This study demonstrated a robust, biocompatible, dual-functioning textured nitric oxide (NO) polyurethane catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. The fabricated catheters exhibited prolonged and controlled NO release that mimics endothelium levels. After the 7 d in vivo model, a significant reduction in platelet adhesion, fibrin mesh, and thrombi was observed on the NO-releasing textured catheters, along with decreased levels of fibrotic tissue decomposition on the jugular vein. Results illustrate that NO-textured catheter surface mitigates foreign body response.

Analysis of standard unit carbon emission and cost assessment of the changing building envelope over material production phase.

It is undeniable that the material production stage is crucial to the whole life cycle of structures. This study proposes the window-to-envelope ratio (WER) based on standard units to determine the inherent relationship between changes in door and window areas and carbon emissions, presuming six distinct types of engineering practices for various buildings are selected. It was concluded that larger door and window areas would result in more embodied carbon emissions. Additionally, as the size of windows and doors increases, the costs and embodied carbon of prefabricated and cast-in-place construction become more comparable. According to the analysis, when the building scale is larger and the door and window opening area is also larger, prefabrication has more potential for saving carbon than cast-in-place building, but with a cost of approximately 10-20% higher. Considering the perspective of consumers, producers, and markets, this study revealed a costing assessment methodology based on standard units for prefabricated structures. In this methodology, producers choose and create various residential layouts based on the distinctive requirements of consumers, while tracking the trends in carbon emissions and production costs. This assessment method tries to create a favorable atmosphere for moral market activity and offers an acceptable solution for the trade-off between environmental and economic factors throughout the material production phase of the building.

An Analysis of Incident Reports Related to Electronic Medication Management: How They Change Over Time.

OBJECTIVE: Electronic medication management (EMM) systems have been shown to introduce new patient safety risks that were not possible, or unlikely to occur, with the use of paper charts. Our aim was to examine the factors that contribute to EMM-related incidents and how these incidents change over time with ongoing EMM use. METHODS: Incidents reported at 3 hospitals between January 1, 2010, and December 31, 2019, were extracted using a keyword search and then screened to identify EMM-related reports. Data contained in EMM-related incident reports were then classified as unsafe acts made by users and the latent conditions contributing to each incident. RESULTS: In our sample, 444 incident reports were determined to be EMM related. Commission errors were the most frequent unsafe act reported by users (n = 298), whereas workarounds were reported in only 13 reports. User latent conditions (n = 207) were described in the highest number of incident reports, followed by conditions related to the organization (n = 200) and EMM design (n = 184). Over time, user unfamiliarity with the system remained a key contributor to reported incidents. Although fewer articles to electronic transfer errors were reported over time, incident reports related to the transfer of information between different computerized systems increased as hospitals adopted more clinical information systems. CONCLUSIONS: Electronic medication management-related incidents continue to occur years after EMM implementation and are driven by design, user, and organizational conditions. Although factors contribute to reported incidents in varying degrees over time, some factors are persistent and highlight the importance of continuously improving the EMM system and its use.

Assessment of land use change of ecological green wedge and cooling island effect: A case study of Wuhan, China.

The construction of urban ecological green wedges, which can mitigate the heat island effect through cooling and ventilation effects, is an important way to enhance the adaptation of cities to climate change. Dynamic monitoring and periodic assessment of both the conservation status and cooling effect of ecological green wedges is a key to ensure the heat mitigation benefits. Based on multi-source remote sensing data, we systematically analyzed the land use changes of six ecological green wedges in Wuhan in 2013 and 2020 using the methods of Markov transfer matrix, land use dynamics, and comprehensive index of land use degree, and evaluated the changes in surface temperature of the ecological green wedges and their cooling island effect. Results showed that the ecological green wedges in Wuhan generally had a large amount of construction land encroaching on ecological land from 2013 to 2020, with the water decreased the most. With the continuous deterioration of ecological green wedges, their land surface temperatures showed rising trends, together with significant weakening trends in cooling island effects. Among all the six wedges, the Dadonghu, Tangxun, and Wuhu exhibited relatively better ecological conservation, slighter land use change and lower overall development degree. Qinglinghu and Houguanhu demonstrated average levels of conservation. Fuhe experienced the most severe change under the significant influence of the westward policy of Wuhan City, with the proportion of water decreasing by 7.1%, warming up by 3.00 ℃, and the largest reduction in cooling distance for the cooling island effect, amounting to about 210 m. The results provided scientific evidence for the urban heat island mitigation-oriented planning and management of ecological green wedges for Wuhan City.

Suspended sediment dynamics and the related environmental risk assessment in a sensitive water area.

Suspended sediment (SS) is a natural component of aquatic environments. It is characterized by the adsorption of pollutants, and its physical properties can affect water volume quality. In this study, SS dynamics were simulated using a 2D hydrodynamic model in the Nanji Mountain Nature Reserve (NNR), and the fluxes of pollutants caused by SS were calculated to assess the biological risks during the wet (May-August) and dry (November-March) seasons. High spatial and temporal variability in SS load within the NNR was found in this study. The average SS load in the reserve increased and then decreased during the year, and the SS input from Ganjiang significantly affected the SS load in the NNR (p < 0.01). The SS load uptrend in the NNR occurred later than that of Ganjiang during the wet season because of the SS sedimentation in the NNR. And the suspension of SS in the NNR during the dry season resulted in a later SS load downtrend compared to Ganjiang. High SS load from Ganjiang during the wet season was responsible for the high nutrient and microplastic fluxes in the NNR, which were 8.38 and 10.61 times higher than those in the dry season, respectively. And the pollutant fluxes during the wet season were almost all from Ganjiang. In contrast, higher waterbird diversity and population during the dry season is the main reason for the increased biological risk of contaminants. Therefore, monitoring and managing SS and its contamination concentrations in rivers entering the lake is helpful for the protection of ecologically sensitive areas and key species in the lake.

Reliability of the Montreal Cognitive Assessment in people with stroke.

This study examined the relative and absolute reliability of the Taiwanese version of the MoCA (MoCA-T) in people with stroke. The study recruited 114 individuals who were at least 3 months after the onset of a first-ever unilateral stroke. The MoCA-T was administered twice, at a 6-week interval, to all participants. The relative reliability was assessed using the intraclass correlation coefficient (ICC), and the absolute reliability was assessed using standard error of measurement (SEM), the smallest real difference (SRD), the SRD percentage, and the Bland-Altman method. The ICC analysis showed the MoCA-T was highly reliable (ICC = 0.85). The absolute reliability was between an acceptable and excellent level, where the SEM and the SRD at the 95% confidence interval were 1.38 and 3.83, respectively. The Bland-Altman analyses showed no systematic bias between repeated measurements. The range of the 95% limits of agreement was narrow, indicating a high level of stability over time. These findings suggest that the MoCA-T has high agreement between repeated measurements without systematic bias. The threshold to detect real change stands between an acceptable and excellent level. The MoCA-T is a reliable tool for cognitive screening in stroke rehabilitation.

Quality of life after brain injury-overall scale, Japanese version: assessment of reliability and validity.

This study analyzed the linguistic and psychometric validation of the Japanese version of the Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) consisting of six items which cover several TBI-relevant domains. We hypothesized that the Japanese version has good reliability, convergent validity, and divergent validity, compared with its long version, the 37-item QOLIBRI. The QOLIBRI-OS Japanese version was forward and back-translated from the English version. In total, 129 individuals participated in this study after experiencing a traumatic brain injury and attending clinics, rehabilitation centers, and support centers in Japan. The structure of the QOLIBRI-OS was investigated by confirmatory factor analyses and compared with the QOLIBRI. Only one factor was extracted, and a model with one underlying factor had a good fit. The QOLIBRI-OS showed good-to-excellent internal consistency and test-retest reliability. The QOLIBRI-OS was positively correlated with the QOLIBRI, Short Form Health Survey-36 version 2, and Glasgow Outcome Scale Extended, and negatively correlated with the Hospital Anxiety and Depression Scale. The results suggest that the QOLIBRI-OS Japanese version is a reliable and valid tool for assessing disease-specific health-related QOL in individuals after traumatic brain injury in Japan.

Evaluation of Appropriate Conditions for Efficient Simultaneous Determination of US EPA and EU Priority Polycyclic Aromatic Hydrocarbons in Various Food Categories and Assessment of Their Consumption Risk.

The QuEChERS (quick, easy, cheap, effective, rugged and safe) conditions were optimized for efficient determination of the U.S. Environmental Protection Agency (US EPA) and European Union (EU) priority polycyclic aromatic hydrocarbons (PAHs) for the categories of grains, tuber & starchy vegetables, soy beans and products, fish & seafood, and poultry & meat, including raw materials and their corresponding products. The PAHs were analyzed using ultrahigh-performance liquid chromatography with temperature-controlled fluorescence detection and gas chromatography with tandem mass spectrometry. The established conditions had good accuracy, repeatability, and precision. Environmental pollution and processing methods influence the level of PAHs in samples. The low molecular weight PAHs were present in all raw materials, and processing increased high and low molecular weight PAHs in the products. The excess cancer risk for consumption of PAHs in cooked samples was mostly acceptable; a small number of samples might be of slight concern in certain age groups.

Trends of Hepatocellular Carcinoma (HCC) Inpatients Mortality and Financial Burden From 2011 to 2017: A Nationwide Analysis.

INTRODUCTION: Liver cancer, including Hepatocellular carcinoma (HCC) is the seventh most common tumor worldwide. Previously, the financial burden of HCC in the United States between 2002 and 2011 was noted to be continuously increasing. This study aims to evaluate temporal trends of hospitalizations due to HCC. METHOD: This is a retrospective analysis utilizing the National Inpatient Sample (NIS) database. All subjects admitted between 2011 and 2017 with a diagnosis of HCC were identified. The primary trend characteristics were in-hospital mortality, hospital charges, and length of stay. RESULTS: An increase in hospitalization from 67,779 (0.18%) admissions in 2011 to 84,580 (0.23%) admissions in 2017( P <0.05) was noted. Most patients were 45 to 64 years old (median 50%), predominantly men (median 68%) ( P <0.05). The primary health care payer was Medicare (Median 49%) and Medicaid (Median 18%) ( P <0.05). The most common geographical location was the south (Median 36%) ( P <0.05). Most patients were admitted to large hospitals (Median 62%) in urban areas ( P <0.05). The median inpatient mortality was estimated to be 9% in 2017 ( P <0.05), which has decreased from 10%( P <0.05) in 2011. The total charges per admission have increased steadily from $58,406 in 2011 to $78,791 in 2017 ( P <0.05). The median length of stay has increased from 5.79 (SD 6.93) in 2011 to 6.07 (SD 8.3) in 2017( P <0.05). The most common mortality risk factor was sepsis, Acute renal failure, and GI hemorrhage. CONCLUSION: HCC-related admissions continue to be on the rise. HCC mortality has decreased across the years with earlier diagnoses and advances in therapy. However, we observed a significant increase in financial burden on health care with increasing in-hospital costs, a finding that needs to be verified in prospective trials.

Assessment of Heart Rate Monitoring During Exercise With Smart Wristbands and a Heart Rhythm Patch: Validation and Comparison Study.

BACKGROUND: The integration of wearable devices into fitness routines, particularly in military settings, necessitates a rigorous assessment of their accuracy. This study evaluates the precision of heart rate measurements by locally manufactured wristbands, increasingly used in military academies, to inform future device selection for military training activities. OBJECTIVE: This research aims to assess the reliability of heart rate monitoring in chest straps versus wearable wristbands. METHODS: Data on heart rate and acceleration were collected using the Q-Band Q-69 smart wristband (Mobile Action Technology Inc) and compared against the Zephyr Bioharness standard measuring device. The Lin concordance correlation coefficient, Pearson product moment correlation coefficient, and intraclass correlation coefficient were used for reliability analysis. RESULTS: Participants from a Northern Taiwanese medical school were enrolled (January 1-June 31, 2021). The Q-Band Q-69 demonstrated that the mean absolute percentage error (MAPE) of women was observed to be 13.35 (SD 13.47). Comparatively, men exhibited a lower MAPE of 8.54 (SD 10.49). The walking state MAPE was 7.79 for women and 10.65 for men. The wristband's accuracy generally remained below 10% MAPE in other activities. Pearson product moment correlation coefficient analysis indicated gender-based performance differences, with overall coefficients of 0.625 for women and 0.808 for men, varying across walking, running, and cooldown phases. CONCLUSIONS: This study highlights significant gender and activity-dependent variations in the accuracy of the MobileAction Q-Band Q-69 smart wristband. Reduced accuracy was notably observed during running. Occasional extreme errors point to the necessity of caution in relying on such devices for exercise monitoring. The findings emphasize the limitations and potential inaccuracies of wearable technology, especially in high-intensity physical activities.

Digital economy: an effective path for promoting residents' health in China.

The primary prerequisite for socioeconomic growth is good health, hence promoting residents' health is a vital objective of public policies. It is yet up for debate whether or not the digital economy (DE), which will be crucial to future economic growth, will eventually result in improvements in residents' health. Utilizing the China Family Panel Studies (CFPS) data in 2020, we explore how the DE affects residents' health. The findings reveal that residents' health is greatly enhanced by the DE. The eastern region sees a more dramatic improvement in residents' health as a result of the DE. Additionally, the DE can improve residents' health through the promotion of regional green development. The study's findings add to our knowledge of how the DE impacts residents' health while also offering recommendations for achieving universal health.

Network pharmacology‒based analysis of marine cyanobacteria derived bioactive compounds for application to Alzheimer's disease.

In recent years, the Alzheimer's disease (AD) epidemic has become one of the largest global healthcare crises. Besides, the available systemic therapies for AD are still inadequate. Due to the insufficient therapeutic options, new treatment strategies are urgently needed to achieve a satisfactory therapeutic effect. Marine bio-resources have been accepted as one of the most economically viable and sustainable sources with potential applications for drug discovery and development. In this study, a marine cyanobacteria-Synechococcus sp. XM-24 was selected as the object of research, to systematically investigate its therapeutic potential mechanisms for AD. The major active compounds derived from the Synechococcus sp. biomass were identified via pyrolysis-gas chromatography-mass spectrometry (GC-MS), and 22 compounds were identified in this strain. The most abundant chemical compounds was (E)-octadec-11-enoic acid, with the peak area of 30.6%. Follow by tridecanoic acid, 12-methyl- and hexadecanoic acid, with a peak area of 23.26% and 18.23%, respectively. GC-MS analysis also identified indolizine, isoquinoline, 3,4-dihydro- and Phthalazine, 1-methyl-, as well as alkene and alkane from the strain. After the chemical toxicity test, 10 compounds were finally collected to do the further analysis. Then, network pharmacology and molecular docking were adopted to systematically study the potential anti-AD mechanism of these compounds. Based on the analysis, the 10 Synechococcus-derived active compounds could interact with 128 related anti-AD targets. Among them, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA) and mitogen-activated protein kinase 3 (MAPK3) were the major targets. Furthermore, the compounds N-capric acid isopropyl ester, (E)-octadec-11-enoic acid, and 2H-Pyran-2,4(3H)-dione, dihydro-6-methyl- obtained higher degrees in the compounds-intersection targets network analysis, indicating these compounds may play more important role in the process of anti-AD. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these active compounds exert the anti-AD effects mainly through PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction and ras signaling pathway. Our study identified Synechococcus-derived bioactive compounds have the potential for application to AD by targeting multiple targets and related pathways, which will provide a foundation for future research on applications of marine cyanobacteria in the functional drug industry.

Human Poisoning with Chlorpyrifos and Cypermethrin Pesticide Mixture: Assessment of Clinical Outcome of Cases Admitted in a Tertiary Care Hospital in Taiwan.

Background and Purpose: There is an overall paucity of data regarding the human toxicity of chlorpyrifos and cypermethrin pesticide mixture. Both organophosphate and pyrethroid insecticides are metabolized by carboxylesterases. Thus, its pesticide combination, organophosphates may boost the toxicity of pyrethroids via inhibited its detoxification by carboxylesterases. This study examined the clinical course, laboratory tests, and outcomes of patients with chlorpyrifos, cypermethrin or their pesticide mixture poisoning, and to determine what association, if any, might exist between these findings. Patients and Methods: Between 2000 and 2021, 121 patients poisoned with chlorpyrifos, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. Patients were categorized as chlorpyrifos (n=82), cypermethrin (n=27) or chlorpyrifos and cypermethrin (n=12) groups. Demographic, clinical, laboratory and mortality data were collected for analysis. Results: The patients experienced a broad range of clinical symptoms, including aspiration pneumonia (44.6%), salivation (42.5%), acute respiratory failure (41.3%), acute kidney injury (13.9%), seizures (7.5%), hypotension (2.6%), etc. Leukocytosis (12,700±6600 /uL) and elevated serum C-reactive protein level (36.8±50.4 mg/L) were common. The acute respiratory failure rate was 41.3%, comprising 48.8% in chlorpyrifos, 11.1% in cypermethrin as well as 58.3% in chlorpyrifos and cypermethrin poisoning. Patients with chlorpyrifos and cypermethrin pesticide mixture poisoning suffered higher rates of acute respiratory failure (P=0.001) and salivation (P=0.001), but lower Glasgow Coma Scale score (P=0.011) and serum cholinesterase level (P<0.001) than other groups. A total of 17 (14.0%) patients expired. The mortality rate was 14.0%, including 17.1% in chlorpyrifos, 3.7% in cypermethrin as well as 16.7% in chlorpyrifos and cypermethrin poisoning. No significant differences in mortality rate were noted (P=0.214). Conclusion: Chlorpyrifos pesticide accounted for the major toxicity of the pesticide mixture. While the data show a higher rate of respiratory failure in the chlorpyrifos and cypermethrin pesticide mixture group than others, other measures of toxicity such as mortality and length of stay were not increased.

Highly reproducible and cost-effective one-pot organoid differentiation using a novel platform based on PF-127 triggered spheroid assembly.

Organoid technology offers sophisticatedin vitrohuman models for basic research and drug development. However, low batch-to-batch reproducibility and high cost due to laborious procedures and materials prevent organoid culture standardization for automation and high-throughput applications. Here, using a novel platform based on the findings that Pluronic F-127 (PF-127) could trigger highly uniform spheroid assembly through a mechanism different from plate coating, we develop a one-pot organoid differentiation strategy. Using our strategy, we successfully generate cortical, nephron, hepatic, and lung organoids with improved reproducibility compared to previous methods while reducing the original costs by 80%-95%. In addition, we adapt our platform to microfluidic chips allowing automated culture. We showcase that our platform can be applied to tissue-specific screening, such as drug toxicity and transfection reagents testing. Finally, we generateNEAT1knockout tissue-specific organoids and showNEAT1modulates multiple signaling pathways fine-tuning the differentiation of nephron and hepatic organoids and suppresses immune responses in cortical organoids. In summary, our strategy provides a powerful platform for advancing organoid research and studying human development and diseases.

Automatic segmentation of the female pelvic floor muscles on MRI for pelvic floor function assessment.

Background: Pelvic organ prolapse (POP) is a pelvic floor dysfunction disease which affects females. The volume of pelvic floor muscle, especially the levator ani muscle (LAM), is an important indicator of pelvic floor function. However, muscle volume measurements depend on manual segmentation, which is clinically time-consuming. In this work, we present an efficient automatic segmentation model of pelvic floor muscles with magnetic resonance imaging (MRI) based on DenseUnet, to achieve muscle volume calculation and provide a reference for the assessment of pelvic floor function. Methods: A total of 49 female pelvic floor magnetic resonance (MR) series were retrospectively enrolled from the First Affiliated Hospital of Army Military Medical University between 2013 and 2021, including 21 normal participants and 28 patients with stage 1-4 POP. The LAM, internal obturator muscle (IOM), and external anal sphincter (EAS) were manually segmented. An improved DenseUnet was proposed for automatic segmentation of these 3 muscles. The Dice similarity coefficient (DSC), Hausdorff distance (HD), and average symmetrical surface distance (ASSD) were used to evaluate segmentation results. The segmentation performance of the improved DenseUnet was compared with those of standard DenseUnet, ResUnet, Unet++, and Unet. Results: The improved DenseUnet showed a good performance. The average DSC and standard deviation of the LAM, IOM, and EAS was 0.758±0.151, 0.716±0.173, and 0.810±0.147, respectively. The average HD was 22.41, 19.00, and 36.01 mm, respectively; and the average ASSD was 3.66, 3.80, and 5.23 mm, respectively. The average DSC and standard deviation of the normal group and POP group was 0.779±0.166 and 0.757±0.154, respectively. There was no significant difference between the muscle volume of the improved DenseUnet and manual segmentation (all P values >0.05). The average total segmentation time for 1 case was 10.18 s on our setup, which is much lower than the manual segmentation time of 45 minutes. Conclusions: The improved DenseUnet segments the pelvic floor muscles in MRI quickly and efficiently, with good precision and faster speed than those of manual segmentation. This can assist doctors in quickly segmenting pelvic floor muscles, calculating muscle volume, and further evaluating pelvic floor function.

Optimizing Precision Medicine for Breast Cancer Brain Metastases with Functional Drug Response Assessment.

The development of novel therapies for brain metastases is an unmet need. Brain metastases may have unique molecular features that could be explored as therapeutic targets. A better understanding of the drug sensitivity of live cells coupled to molecular analyses will lead to a rational prioritization of therapeutic candidates. We evaluated the molecular profiles of 12 breast cancer brain metastases (BCBM) and matched primary breast tumors to identify potential therapeutic targets. We established six novel patient-derived xenograft (PDX) from BCBM from patients undergoing clinically indicated surgical resection of BCBM and used the PDXs as a drug screening platform to interrogate potential molecular targets. Many of the alterations were conserved in brain metastases compared with the matched primary. We observed differential expressions in the immune-related and metabolism pathways. The PDXs from BCBM captured the potentially targetable molecular alterations in the source brain metastases tumor. The alterations in the PI3K pathway were the most predictive for drug efficacy in the PDXs. The PDXs were also treated with a panel of over 350 drugs and demonstrated high sensitivity to histone deacetylase and proteasome inhibitors. Our study revealed significant differences between the paired BCBM and primary breast tumors with the pathways involved in metabolisms and immune functions. While molecular targeted drug therapy based on genomic profiling of tumors is currently evaluated in clinical trials for patients with brain metastases, a functional precision medicine strategy may complement such an approach by expanding potential therapeutic options, even for BCBM without known targetable molecular alterations. Significance: Examining genomic alterations and differentially expressed pathways in brain metastases may inform future therapeutic strategies. This study supports genomically-guided therapy for BCBM and further investigation into incorporating real-time functional evaluation will increase confidence in efficacy estimations during drug development and predictive biomarker assessment for BCBM.

Association between vehicle ownership and disparities in mortality after myocardial infarction.

Background: Access to reliable transportation is fundamental in the management of chronic disease. The purpose of this study was to investigate the association between vehicle ownership at the neighborhood-level and long-term mortality after myocardial infarction (MI). Methods: This is a retrospective observational study evaluating adult patients admitted for MI between January 1st, 2006, and December 31st, 2016. Neighborhoods were defined by census tract and household vehicle ownership data was obtained from the American Community Survey courtesy of the University of California, Los Angeles Center for Neighborhood Knowledge. Patients were divided into 2 groups: those living in neighborhoods with higher vehicle ownership, and those living in neighborhoods with lower vehicle ownership. The cutoff of 4.34% of households reporting not owning a vehicle was used to define a neighborhood as one with "higher" vs "lower" vehicle ownership as this was the median value for the cohort. The association between vehicle ownership and all-cause mortality after MI was assessed using Cox proportional hazards regression models. Results: A total of 30,126 patients were included (age 68.1 +/- 13.5 years, 63.2% male). After adjusting for age, sex, race/ethnicity, and medical comorbidities, lower vehicle ownership was associated with increased all-cause mortality after MI (hazard ratio [HR] 1.10; 95% confidence interval [CI] 1.06-1.14; p<0.001). This finding remained significant after adjusting for median household income (HR 1.06; 95% CI 1.02-1.10; p = 0.007). Upon comparison of White and Black patients living in neighborhoods with lower vehicle ownership; Black patients were found to have an increased all-cause mortality after MI (HR 1.21, 95% CI 1.13-1.30, p<0.001), a difference which remained significant after adjusting for income (HR 1.20; 95% CI 1.12-1.29; p<0.001). There was no significant difference in mortality between White and Black patients living in neighborhoods with higher vehicle ownership. Conclusion: Lower vehicle ownership was associated with increased mortality after MI. Black patients living in neighborhoods with lower vehicle ownership had a higher mortality after MI than White patients living in similar neighborhoods but Black patients living in neighborhoods with higher vehicle ownership had no worse mortality than their White counterparts. This study highlights the importance of transportation in determining health status after MI.

Assessment of various conditions for the simultaneous determination of US EPA and EU priority PAHs in coffee samples and their PAHs consumption risk.

The optimal conditions for simultaneous determination of the U.S. Environmental Protection Agency (US EPA) and European Union (EU) priority polycyclic aromatic hydrocarbons (PAHs) in coffee beans and coffee brews were developed. The QuEChERS (quick, easy, cheap, effective, rugged and safe) technology combined with high performance liquid chromatography - temperature-controlled fluorescence detection and gas chromatography - tandem mass spectrometry were used in the investigation. PAHs could be determined in commercially available green coffee beans (possibly caused by environmental contamination), and their PAHs content increased with the degree of roasting. Coffee beans brewed with the coffee machine released more PAHs into their brews than those brewed with the drip bag. The PAHs consumption risk of the brewed coffee samples was not high due to their low PAH level. Nevertheless, the methods of roasting and brewing and the amount of drinking could still be considered to reduce the intake of PAHs.

Comprehensive Assessment of the Clinical Risk Factors of Postoperative Adverse Events and Survival in Patients With Non-small-cell Lung Cancer.

BACKGROUND/AIM: Postoperative adverse events are associated with poor clinical outcomes and survival in patients with non-small-cell lung cancer (NSCLC) treated with curative operation. However, comprehensive evaluation of the clinical characteristics associated with postoperative adverse events and survival outcomes is lacking. PATIENTS AND METHODS: A retrospective study that evaluated patients with NSCLC who underwent curative surgery between 2008 and 2019 was conducted in a medical center. The baseline characteristics, five-item modified frailty index, sarcopenia, inflammatory biomarkers, surgical approach, postoperative adverse events, and survival were statistically analyzed. RESULTS: Patients with a history of smoking and preoperative sarcopenia were at a higher risk of developing postoperative pulmonary complications. Smoking, frailty, and traditional open thoracotomy (OT) were associated with infections, and sarcopenia was identified as a risk factor for major complications. Advanced tumor stage, high neutrophil-to-lymphocyte ratio, OT, major complications, and infections were identified as risk factors for overall and disease-free survival. CONCLUSION: Pre-treatment sarcopenia was found to be a predictor of major complications. Infections and major complications were associated with survival outcomes in patients with NSCLC.