Using Discrete Event Simulation to Design and Assess an AI-aided Workflow for Same-day Diagnostic Testing of Women Undergoing Breast Screening.

The process of patients waiting for diagnostic examinations after an abnormal screening mammogram is inefficient and anxiety-inducing. Artificial intelligence (AI)-aided interpretation of screening mammography could reduce the number of recalls after screening. We proposed a same-day diagnostic workup to alleviate patient anxiety by employing an AI-aided interpretation to reduce unnecessary diagnostic testing after an abnormal screening mammogram. However, the potential unintended consequences of introducing this workflow in a high-volume breast imaging center are unknown. Using discrete event simulation, we observed that implementing the AI-aided screening mammogram interpretation and same-day diagnostic workflow would reduce daily patient volume by 4%, increase the time a patient would be at the clinic by 24%, and increase waiting times by 13-31%. We discuss how changing the hours of operation and introducing new imaging equipment and personnel may alleviate these negative impacts.

Factors Associated With Nonadherence to Lung Cancer Screening Across Multiple Screening Time Points.

Importance: Screening with low-dose computed tomography (CT) has been shown to reduce mortality from lung cancer in randomized clinical trials in which the rate of adherence to follow-up recommendations was over 90%; however, adherence to Lung Computed Tomography Screening Reporting & Data System (Lung-RADS) recommendations has been low in practice. Identifying patients who are at risk of being nonadherent to screening recommendations may enable personalized outreach to improve overall screening adherence. Objective: To identify factors associated with patient nonadherence to Lung-RADS recommendations across multiple screening time points. Design, Setting, and Participants: This cohort study was conducted at a single US academic medical center across 10 geographically distributed sites where lung cancer screening is offered. The study enrolled individuals who underwent low-dose CT screening for lung cancer between July 31, 2013, and November 30, 2021. Exposures: Low-dose CT screening for lung cancer. Main Outcomes and Measures: The main outcome was nonadherence to follow-up recommendations for lung cancer screening, defined as failing to complete a recommended or more invasive follow-up examination (ie, diagnostic dose CT, positron emission tomography-CT, or tissue sampling vs low-dose CT) within 15 months (Lung-RADS score, 1 or 2), 9 months (Lung-RADS score, 3), 5 months (Lung-RADS score, 4A), or 3 months (Lung-RADS score, 4B/X). Multivariable logistic regression was used to identify factors associated with patient nonadherence to baseline Lung-RADS recommendations. A generalized estimating equations model was used to assess whether the pattern of longitudinal Lung-RADS scores was associated with patient nonadherence over time. Results: Among 1979 included patients, 1111 (56.1%) were aged 65 years or older at baseline screening (mean [SD] age, 65.3 [6.6] years), and 1176 (59.4%) were male. The odds of being nonadherent were lower among patients with a baseline Lung-RADS score of 1 or 2 vs 3 (adjusted odds ratio [AOR], 0.35; 95% CI, 0.25-0.50), 4A (AOR, 0.21; 95% CI, 0.13-0.33), or 4B/X, (AOR, 0.10; 95% CI, 0.05-0.19); with a postgraduate vs college degree (AOR, 0.70; 95% CI, 0.53-0.92); with a family history of lung cancer vs no family history (AOR, 0.74; 95% CI, 0.59-0.93); with a high age-adjusted Charlson Comorbidity Index score (≥4) vs a low score (0 or 1) (AOR, 0.67; 95% CI, 0.46-0.98); in the high vs low income category (AOR, 0.79; 95% CI, 0.65-0.98); and referred by physicians from pulmonary or thoracic-related departments vs another department (AOR, 0.56; 95% CI, 0.44-0.73). Among 830 eligible patients who had completed at least 2 screening examinations, the adjusted odds of being nonadherent to Lung-RADS recommendations at the following screening were increased in patients with consecutive Lung-RADS scores of 1 to 2 (AOR, 1.38; 95% CI, 1.12-1.69). Conclusions and Relevance: In this retrospective cohort study, patients with consecutive negative lung cancer screening results were more likely to be nonadherent with follow-up recommendations. These individuals are potential candidates for tailored outreach to improve adherence to recommended annual lung cancer screening.

Turn-on fluorescent capsule for selective fluoride detection and water purification.

It has been a long-standing challenge to develop organic molecular capsules for selective anion binding in water. Here, selective recognition of aqueous fluoride was achieved through triple protonation of a hemicryptophane (L), which is composed of a fluorescent cyclotriveratrylene (CTV) cap and tris(2-aminoethyl)amine (tren) as the anion binding site. Fluoride encapsulation by [3H-L]3+ was evidenced by 1H NMR, 19F NMR, LC-MS, and X-ray crystallography. In addition, [3H-L]3+ exhibited a 'turn-on' fluorescence signal (λ em = 324 nm) upon fluoride addition. An apparent association constant K A = (7.5 ± 0.4) × 104 M-1 and a detection limit of 570 nM fluoride were extracted from the fluorescence titration experiments in citrate buffer at pH 4.1. To the best of our knowledge, [3H-L]3+ is the first example of a metal-free molecular capsule that reports on fluoride binding in purely aqueous solutions with a fluorescence response. Finally, the protonated capsule was supported on silica gel, which enabled adsorptive removal of stoichiometric fluoride from water and highlights real-world applications of this organic host-guest chemistry.

Counteranions at Peripheral Sites Tune Guest Affinity for a Protonated Hemicryptophane.

The affinity of small molecules for biomolecular cavities is tuned through a combination of primary and secondary interactions. It has been challenging to mimic these features in organic synthetic host molecules, however, where the cavities tend to be highly symmetric and nonpolar, and less amenable to chemical manipulation. Here, a host molecule composed of a TREN ligand and cyclotriveratrylene moiety was investigated. Size-matched polar guests were encapsulated within the cavity via triple protonation of the TREN moiety with various sulfonic acids. X-ray crystallography confirmed guest encapsulation and identified three methanesulfonates, p-toluenesulfonates, or 2-naphthalenesulfonates hydrogen-bonded with H3TREN at the periphery of the cavity. These structurally diverse counteranions were shown by 1H NMR spectroscopy to differentially regulate guest access at the three portals, and to undergo competitive displacement in solution. This work reveals "counteranion tuning" to be a simple and powerful strategy for modulating host-guest affinity, as applied here in a TREN-hemicryptophane.

Capturing Demographic, Health-Related, and Psychosocial Variables in a Standardized Manner: Towards Improving Cancer Screening Adherence.

Determining factors influencing patient participation in and adherence to cancer screening recommendations is key to successful cancer screening programs. However, the collection of variables necessary to anticipate patient behavior in cancer screening has not been systematically examined. Using lung cancer screening as a representative example, we conducted an exploratory analysis to characterize the current representations of 18 demographic, health-related, and psychosocial variables collected as part of a conceptual model to understand factors for lung cancer screening participation and adherence. Our analysis revealed a lack of standardization in controlled terminologies and common data elements for these variables. For example, only eight (44%) demographic and health-related variables were recorded consistently in the electronic health record. Multiple survey instruments could collect the remaining variables but were highly inconsistent in how variables were represented. This analysis suggests opportunities to establish standardized data formats for psychological, cognitive, social, and environmental variables to improve data collection.

Patient Adherence to Lung CT Screening Reporting & Data System-Recommended Screening Intervals in the United States: A Systematic Review and Meta-Analysis.

Lung cancer screening (LCS) is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS). Nevertheless, patient adherence to recommended intervals varies, potentially diminishing benefit from screening. We conducted a systematic review and meta-analysis of patient adherence to Lung-RADS-recommended screening intervals. We systematically searched MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and major radiology and oncology conference archives between April 28, 2014, and December 17, 2020. Eligible studies mentioned patient adherence to the recommendations of Lung-RADS. The review protocol was registered with PROSPERO (CRD42020189326). We identified 24 eligible studies for qualitative summary, of which 21 were suitable for meta-analysis. The pooled adherence rate was 57% (95% confidence interval: 46%-69%) for defined adherence (e.g., an annual incidence screen was performed within 15 mo) among 6689 patients and 65% (95% confidence interval: 55%-75%) for anytime adherence among 5085 patients. Large heterogeneity in adherence rates between studies was observed (I2 = 99% for defined adherence, I2 = 98% for anytime adherence). Heterogeneous adherence rates were associated with Lung-RADS scores, with significantly higher adherence rates among Lung-RADS 3 to 4 than Lung-RADS 1 to 2 (p < 0.05). Patient adherence to Lung-RADS-recommended screening intervals is suboptimal across clinical LCS programs in the United States, especially among patients with results of Lung-RADS categories 1 to 2. To improve adherence rates, future research may focus on implementing tailored interventions after identifying barriers to LCS. We also propose a minimum standardized set of data elements for future pooled analyses of LCS adherence on the basis of our findings.

Monomeric Cryptophane with Record-High Xe Affinity Gives Insights into Aggregation-Dependent Sensing.

Cryptophane host molecules provide ultrasensitive contrast agents for 129Xe NMR/MRI. To investigate key features of cryptophane-Xe sensing behavior, we designed a novel water-soluble cryptophane with a pendant hydrophobic adamantyl moiety, which has good affinity for a model receptor, beta-cyclodextrin (ß-CD). Adamantyl-functionalized cryptophane-A (AFCA) was synthesized and characterized for Xe affinity, 129Xe NMR signal, and aggregation state at varying AFCA and ß-CD concentrations. The Xe-AFCA association constant was determined by fluorescence quenching, KA = 114,000 ± 5000 M-1 at 293 K, which is the highest reported affinity for a cryptophane host in phosphate-buffered saline (pH 7.2). No hyperpolarized (hp) 129Xe NMR peak corresponding to AFCA-bound Xe was directly observed at high (100 µM) AFCA concentration, where small cryptophane aggregates were observed, and was only detected at low (15 µM) AFCA concentration, where the sensor remained fully monomeric in solution. Additionally, we observed no change in the chemical shift of AFCA-encapsulated 129Xe after ß-CD binding to the adamantyl moiety and a concomitant lack of change in the size distribution of the complex, suggesting that a change in the aggregation state is necessary to elicit a 129Xe NMR chemical shift in cryptophane-based sensing. These results aid in further elucidating the recently discovered aggregation phenomenon, highlight limitations of cryptophane-based Xe sensing, and offer insights into the design of monomeric, high-affinity Xe sensors.

EDICNet: An end-to-end detection and interpretable malignancy classification network for pulmonary nodules in computed tomography.

We present an interpretable end-to-end computer-aided detection and diagnosis tool for pulmonary nodules on computed tomography (CT) using deep learning-based methods. The proposed network consists of a nodule detector and a nodule malignancy classifier. We used RetinaNet to train a nodule detector using 7,607 slices containing 4,234 nodule annotations and validated it using 2,323 slices containing 1,454 nodule annotations drawn from the LIDC-IDRI dataset. The average precision for the nodule class in the validation set reached 0.24 at an intersection over union (IoU) of 0.5. The trained nodule detector was externally validated using a UCLA dataset. We then used a hierarchical semantic convolutional neural network (HSCNN) to classify whether a nodule was benign or malignant and generate semantic (radiologist-interpretable) features (e.g., mean diameter, consistency, margin), training the model on 149 cases with diagnostic CTs collected from the same UCLA dataset. A total of 149 nodule-centered patches from the UCLA dataset were used to train the HSCNN. Using 5-fold cross validation and data augmentation, the mean AUC and mean accuracy in the validation set for predicting nodule malignancy achieved 0.89 and 0.74, respectively. Meanwhile, the mean accuracy for predicting nodule mean diameter, consistency, and margin were 0.59, 0.74, and 0.75, respectively. We have developed an initial end-to-end pipeline that automatically detects nodules ≥ 5 mm on CT studies and labels identified nodules with radiologist-interpreted features automatically.

Nitrogen and Sulfur Co-Doped Graphene-Like Carbon from Industrial Dye Wastewater for Use as a High-Performance Supercapacitor Electrode.

Nitrogen and sulfur co-doped graphene-like carbon (N,S-GLC) is successfully prepared in a one-step hydrothermal reaction of glucose with industrial dye wastewater followed by chemical activation. The nitrogen and sulfur are sourced entirely from the industrial wastewater. The process not only provides an alternative way of treating industry wastewater, but also offers a green route for recovering energy from the waste in the form of chemicals. The resultant N,S-GLC shows a good degree of graphitization, a high specific surface area (1734 m2 g-1), and moderate heteroatom doping (N: 2.1 at%, S: 0.7 at%). The N,S-GLC electrode displays high specific capacitance of 275 F g-1 at a current density of 0.5 A g-1 with a retention of 65.4% at 20 A g-1 in 6 m KOH. Moreover, the assembled symmetrical supercapacitor cell shows a capacitance of 38 F g-1 at a current density of 0.5 A g-1, which is equivalent to an energy density of 6.4 Wh kg-1 at a power density of 275.0 W kg-1. This approach provides an alternative and sustainable way of fabricating heteroatom-doped graphene-like carbon materials for use in high-performance supercapacitors.

The Expression of Calprotectin and Factors in TLR4/NF-κB/MyD88 Pathway in Patients with Idiopathic Acute Anterior Uveitis.

Purpose: The purpose of the article is to investigate the contribution of calprotectin and factors in toll-like receptor 4/nuclear factor-κB/myeloid differentiation factor 88 (TLR4/NF-κB/MyD88) pathway in patients with idiopathic acute anterior uveitis (IAAU). Methods: In total, 72 patients with IAAU and 56 healthy individuals were enrolled. Serum calprotectin, TLR-4, and MyD88 were determined. Best-corrected visual acuity, uveitis activity grading, and macular thickness measured by optical coherence tomography were performed. Results: Serum calprotectin, TLR4, and MyD88 levels were higher in IAAU group than those in healthy individuals. Serum calprotectin level was positively correlated with uveitis activity grading and macular thickness. Receiver operating characteristic curve analysis showed serum calprotectin had larger area under curve than serum TLR4 and MyD88. Conclusions: The calprotectin and TLR4/NF-κB/MyD88 signal might contribute to the pathogenesis of IAAU and serum calprotectin might be a specific biomarker for the measurement of ocular inflammation in IAAU.

Dual Functions of Cyclometalated Iridium(III) Complexes: Anti-Metastasis and Lysosome-Damaged Photodynamic Therapy.

Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can effectively inhibit several cancerous processes, including cell migration, invasion, colony formation, and angiogenesis. Interestingly, they show a much higher singlet oxygen quantum yield in an acidic solution than in a neutral solution. Upon irradiation at 425 nm with low energy (1.2 J cm-2), they can induce apoptosis through lysosomal damage, evaluation of reactive oxygen species level, and activation of caspase-3/7. The highest phototoxicity index is >476, with almost no dark cytotoxicity observed for Ir4. Ir4 can also inhibit tumor growth effectively in nude mice in vivo after photodynamic therapy. An in vitro assay against 70 kinases indicates that maternal embryonic leucine zipper kinase (MELK), PIK3CA, and AMPK are the possible molecular targets. The half maximal inhibitory concentration of Ir4 toward MELK is 1.27 µM. Our study demonstrates that these Ir(III) complexes are promising anticancer agents with dual functions, including metastasis inhibition and lysosome-damaged photodynamic therapy.

A phosphorescent rhenium(I) histone deacetylase inhibitor: mitochondrial targeting and paraptosis induction.

In this report, we designed a histone deacetylase-targeted phosphorescent Re(I) complex ReLMito. Colocalization studies suggested that ReLMito could specially localize to mitochondria. We also demonstrated that ReLMito could induce paraptosis in cancer cells. These features endowed the complex with potential to induce and monitor mitochondrial morphological changes during the paraptosis simultaneously.

Strong fluorescence of poly(N-vinylpyrrolidone) and its oxidized hydrolyzate.

Discovering fluorescence of existing compounds, which are generally regarded as non-fluorescent, is of important academic and technical significance. This article reports the fluorescence of common compounds containing pyrrolidone ring(s) and their oxidized hydrolyzates. Poly(N-vinylpyrrolidone) (PVP), polymerized from a very weak fluorescent monomer N-vinyl-2-pyrrolidone (NVP), exhibits strong intrinsic fluorescence. Moreover, the fluorescence of its "hydrolyzate" is dramatically enhanced by about 1000 times. The "hydrolyzate" of N-methyl-pyrrolidone (NMP) also exhibits significantly enhanced fluorescence. By studying the chemical structures and fluorescence of the hydrolyzates, the enhanced fluorescence is attributed to the formation of secondary amine oxide. The much stronger fluorescence of the polymers compared to the corresponding small molecular compounds is ascribed to the "aggregation-induced emission" (AIE) effect of the luminophores. PVP and its oxidized hydrolyzate also show some phenomena different to the common AIE effect. The fluorescence of PVP and its oxidized hydrolyzate shows stimuli response to metal ions and pH values. This study introduces novel fluorescent materials for various potential applications.

Thermal conductivity measurements for small molecule organic solid materials using modulated differential scanning calorimetry (MDSC) and data corrections for sample porosity.

A method for measuring the thermal conductivity (k) of small molecule organic solid materials using modulated differential scanning calorimetry (MDSC) is demonstrated. Sample preparation required powder consolidation, unavoidably introducing air voids into compacts. Supporting equations for the technique were modified to include a porosity term (epsilon), and the theoretical quadratic relationship between k and epsilon was confirmed by experimental measurements for 18 representative materials. Zero-porosity extrapolation was used to approximate values of "true" thermal conductivity for non-porous solids (k(epsilon=0)). Zero-porosity-extrapolated values ranged from 0.1273W/(Km) to 0.3472W/(Km) for all materials, consistent with expected values of k for non-porous organic polymers.

Informatic calibration of a materials properties database for predictive assessment of mechanically activated disordering potential for small molecule organic solids.

The potential for small molecule organic crystalline materials to become disordered as a result of high shear mechanical processing was investigated. A data-driven model was generated from a database of critical materials properties, which were expected to correlate with the potential of a small molecule organic crystalline solid to become fully disordered by the application of mechanical energy. The model was compared with a previously published disordering model based on fundamental thermodynamic relationships. Samples of 23 crystalline solids were subjected to extensive comminution under controlled temperature conditions; powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) were used to confirm disordering. Logistic regression was used to investigate the significance of each materials property with respect to the prediction of disordering potential. Seven materials properties (glass transition temperature, melting temperature, heat of fusion, crystallographic density, Young's modulus, molar volume and attachment energy) were identified as having a significant correlation with the potential for material disordering. Stepwise multivariate logistic regression was used to further assess the correlation between disordering potential and each of the seven properties. A linear probability model based on two materials properties (glass transition temperature and molar volume) was developed for the prediction of disordering potential.