Colon Age: A Metric for Whether and How to Screen Male Veterans for Early-Onset Colorectal Cancer.

We aimed to develop a metric for estimating risk for early-onset colorectal cancer (EOCRC) to help decide whether and how to screen persons < age 50. We used risk prediction models derived and validated on male veterans to calculate the RRs for six scenarios: one low-risk scenario (no risk factors present), four intermediate risk scenarios (some risk factors present), and one high-risk scenario (all risk factors present) for three age groups (35-39, 40-44, and 45-49 years). For each scenario, we estimated absolute colorectal cancer risk using Surveillance Epidemiology and End Results colorectal cancer incidence rates and each scenario's RR. We identified the current Surveillance Epidemiology and End Results 5-year age group to which the revised estimate was closest and refer to the midpoint of this group as the "colon age." When the revised estimate equals or exceeds that for 50- to 54-year-olds and for 70- to 74-year-olds, respective recommendations were made for (any) colorectal cancer screening and screening with colonoscopy. Among the scenarios, there was inconsistency between the two models for the 35 to 39 and 40 to 44 age groups, with only the 15-variable model recommending screening for the higher-risk 35- to 39-year-olds. Both models recommended screening for some intermediate risk and high-risk 40- to 44-year-olds. The models were well aligned on whether and how to screen most 45- to 49-year-olds. Using risk factors for EOCRC with colorectal cancer incidence rates, "colon age" may be useful for shared decision-making about whether and how to screen male veterans <50 years. For 45- to 49-year-olds, the 7-variable model may be preferred by patients, providers, and health systems. Prevention Relevance: A new metric known as "colon age" expresses risk of EOCRC based on biological risk and may be useful for providers to explain and for patients to understand colorectal cancer risk when considering whether and how to be screened for colorectal cancer prior to age 45 or 50.

Measuring Heat Dissipation and Entropic Potential in Battery Cathodes Made with Conjugated and Conventional Polymer Binders Using Operando Calorimetry.

This study explores the influence of electronic and ionic conductivities on the behavior of conjugated polymer binders through the measurement of entropic potential and heat generation in an operating lithium-ion battery. Specifically, the traditional poly(vinylidene fluoride) (PVDF) binder in LiNi0.8Co0.15Al0.05O2 (NCA) cathode electrodes was replaced with semiconducting polymer binders based on poly(3,4-propylenedioxythiophene). Two conjugated polymers were explored: one is a homopolymer with all aliphatic side chains, and the other is a copolymer with both aliphatic and ethylene oxide side chains. We have shown previously that both polymers have high electronic conductivity in the potential range of NCA redox, but the copolymer has a higher ionic conductivity and a slightly lower electronic conductivity. Entropic potential measurements during battery cycling revealed consistent trends during delithiation for all of the binders, indicating that the binders did not modify the expected NCA solid solution deintercalation process. The entropic signature of polymer doping to form the conductive state could be clearly observed at potentials below NCA oxidation, however. Operando isothermal calorimetric measurements showed that the conductive binders resulted in less Joule heating compared to PVDF and that the net electrical energy was entirely dissipated as heat. In a comparison of the two conjugated polymer binders, the heat dissipation was lower for the homopolymer binder at lower C-rates, suggesting that electronic conductivity rather than ionic conductivity was the most important for reducing Joule heating at lower rates, but that ionic conductivity became more important at higher rates.

Colon Age: A Metric for Whether and How to Screen Male Veterans for Early-Onset Colorectal Cancer.

We aimed to develop a metric for estimating risk for early-onset colorectal cancer (EOCRC) to help decide whether and how to screen persons < age 50. We used risk prediction models derived and validated on male Veterans to calculate the relative risks (RRs) for 6 scenarios: one low-risk scenario (no risk factors present), four intermediate risk scenarios (some factors present), and one high-risk scenario (all factors present) for three age groups (35-39, 40-44, and 45-49 years). For each scenario, we estimated absolute CRC risk using SEER CRC incidence rates and each scenario's RR. We identified the current SEER 5-year age group to which the revised estimate was closest and refer to the midpoint of this group as the "colon age". When the revised estimate was ≥ that for 50-54-year-olds and for 70-74-year-olds, respective recommendations were made for (any) CRC screening and screening with colonoscopy. Among the scenarios, there was inconsistency between the two models for the 35-39 and 40-44 age groups, with only the 15-variable model recommending screening for the higher-risk 35-to-39-year-olds. Both models recommended screening for some intermediate risk and high-risk 40-44-year-olds. The models were well-aligned on whether and how to screen most 45-49-year-olds. Using risk factors for EOCRC with CRC incidence rates, "colon age" may be useful for shared decision making about whether and how to screen male Veterans < 50 years. For 45-49-year-olds, the 7-variable model may be preferred by patients, providers, and health systems.

Broadening Eligibility Criteria and Diversity among Patients for Cancer Clinical Trials.

BACKGROUND: Certain populations have been historically underrepresented in clinical trials. Broadening eligibility criteria is one approach to inclusive clinical research and achieving enrollment goals. How broadened trial eligibility criteria affect the diversity of eligible participants is unknown. METHODS: Using a nationwide electronic health record-derived deidentified database, we identified a retrospective cohort of patients diagnosed with 22 cancer types between April 1, 2013 and December 31, 2022 who received systemic therapy (N=235,234) for cancer. We evaluated strict versus broadened eligibility criteria using performance status and liver, kidney, and hematologic function around first line of therapy. We performed logistic regression to estimate odds ratios for exclusion by strict criteria and their association with measures of patient diversity, including sex, age, race or ethnicity, and area-level socioeconomic status (SES); estimated the impact of broadening criteria on the number and distribution of eligible patients; and performed Cox regression to estimate hazard ratios for real-world overall survival (rwOS) comparing patients meeting strict versus broadened criteria. RESULTS: When applying common strict cutoffs for eligibility criteria to patients with complete data and weighting each cancer type equally, 48% of patients were eligible for clinical trials. Female (odds ratio, 1.30; 95% confidence interval [CI], 1.25 to 1.35), older (age 75+ vs. 18 to 49 years old: odds ratio, 3.04; 95% CI, 2.85 to 3.24), Latinx (odds ratio, 1.46; 95% CI, 1.39 to 1.54), non-Latinx Black (odds ratio, 1.11; 95% CI, 1.06 to 1.16), and lower-SES patients were more likely to be excluded using strict eligibility criteria. Broadening criteria increased the number of eligible patients by 78%, with the strongest impact for older, female, non-Latinx Black, and lower-SES patients. Patients who met only broadened criteria had worse rwOS versus those with strict criteria (hazard ratio, 1.31; 95% CI, 1.27 to 1.34). CONCLUSIONS: Data-driven evaluation of clinical trial eligibility criteria may optimize the eligibility of certain historically underrepresented groups and promote access to more inclusive trials. (Sponsored by Flatiron Health.).

Control of Properties through Hydrogen Bonding Interactions in Conjugated Polymers.

Molecular design is crucial for endowing conjugated polymers (CPs) with unique properties and enhanced electronic performance. Introducing Hydrogen-bonding (H-bonding) into CPs has been a broadly exploited, yet still emerging strategy capable of tuning a range of properties encompassing solubility, crystallinity, electronic properties, solid-state morphology, and stability, as well as mechanical properties and self-healing properties. Different H-bonding groups can be utilized to tailor CPs properties based on the applications of interest. This review provides an overview of classes of H-bonding CPs (assorted by the different H-bond functional groups), the synthetic methods to introduce the corresponding H-bond functional groups and the impact of H-bonding in CPs on corresponding electronic and materials properties. Recent advances in addressing the trade-off between electronic performance and mechanical durability are also highlighted. Furthermore, insights into future directions and prospects for H-bonded CPs are discussed.

Defining Pathologic Upstaging in cT1b Esophageal Cancer: Should We Consider Neoadjuvant Therapy?

INTRODUCTION: Neoadjuvant chemoradiation therapy (NCRT) for cT1b esophageal cancer is not recommended despite the risk of pathologic upstaging with increased depth of penetration. We aimed to (1) define the rate of and factors associated with pathologic upstaging, (2) describe current trends in treatments, and (3) compare overall survival (OS) with and without NCRT for surgically resected cT1b lesions. METHODS: We used the 2020 National Cancer Database to identify patients with cT1b N0 esophageal cancer with or without pathologic upstaging who underwent removal of their tumor. We built multivariable logistic regression models to assess factors associated with pathologic upstaging. Survival was compared using log-rank analysis and modeled using multivariable Cox proportional hazards regressions. RESULTS: Out of 1106 patients with cT1b esophageal cancer, 17.3% (N = 191) had pathologic upstaging. A higher tumor grade (P = 0.002), greater tumor size (P < 0.001), and presence of lympho-vascular invasion (P < 0.001) were associated with pathologic upstaging. 8.0% (N = 114) of patients were treated with NCRT. Five-y OS was 49.4% for patients who received NCRT compared to 67.2% for upfront esophagectomy (P < 0.05). Pathologic upstaging was associated with decreased OS (pathologic upstaging 43.7% versus no pathologic upstaging 67.7%) (hazard ratio 2.12 [95% confidence interval, 1.70-2.65; P < 0.001]). Compared to esophagectomy, endoscopic local tumor excision was associated with a decreased OS (hazard ratio 1.50 [95% confidence interval, 1.19-1.89; P = 0.001]). CONCLUSIONS: Pathologic upstaging of cT1b lesions is associated with decreased OS. Esophagectomy is associated with a survival benefit over endoscopic local tumor excision for these lesions. NCRT is not associated with an increase in OS in cT1b lesions compared to upfront esophagectomy.

Relating Structure to Properties in Non-Conjugated Pendant Electroactive Polymers.

Non-conjugated pendant electroactive polymers (NCPEPs) are an emerging class of polymers that offer the potential of combining the desirable optoelectronic properties of conjugated polymers with the superior synthetic methodologies and stability of traditional non-conjugated polymers. Despite an increasing number of studies focused on NCPEPs, particularly on understanding fundamental structure-property relationships, no attempts have been made to provide an overview on established relationships to date. This review showcases selected reports on NCPEP homopolymers and copolymers that demonstrate how optical, electronic, and physical properties of the polymers are affected by tuning of key structural variables such as the chemical structure of the polymer backbone, molecular weight, tacticity, spacer length, the nature of the pendant group, and in the case of copolymers the ratios between different comonomers and between individual polymer blocks. Correlation of structural features with improved π-stacking and enhanced charge carrier mobility serve as the primary figures of merit in evaluating impact on NCPEP properties. While this review is not intended to serve as a comprehensive summary of all reports on tuning of structural parameters in NCPEPs, it highlights relevant established structure-property relationships that can serve as a guideline for more targeted design of novel NCPEPs in the future.

Vascularization of the adult mouse lung grafted onto the chick chorioallantoic membrane.

In the later stages of angiogenesis, the vascular sprout transitions into a functional vessel by fusing with a target vessel. Although this process appears to routinely occur in embryonic tissue, the biologic rules for sprout fusion and lumenization in adult regenerating tissue are unknown. To investigate this process, we grafted portions of the regenerating post-pneumonectomy lung onto the chick chorioallantoic membrane (CAM). Grafts from all 4 lobes of the post-pneumonectomy right lung demonstrated peri-graft angiogenesis as reflected by fluorescent plasma markers; however, fluorescent microsphere perfusion primarily occurred in the lobe of the lung that is the dominant site of post-pneumonectomy angiogenesis-namely, the cardiac lobe. Vascularization of the cardiac lobe grafts was confirmed by active tissue growth (p < .05). Functional vascular connections between the cardiac lobe and the CAM vascular network were demonstrated by confocal fluorescence microscopy as well as corrosion casting and scanning electron microscopy (SEM). Bulk transcriptional profiling of the cardiac lobe demonstrated the enhanced expression of many genes relative to alveolar epithelial cell (CD11b-/CD31-) control cells, but only the upregulation of Ereg and Fgf6 compared to the less well-vascularized right upper lobe. The growth of actively regenerating non-neoplastic adult tissue on the CAM demonstrates that functional lumenization can occur between species (mouse and chick) and across the developmental spectrum (adult and embryo).

Berry Curvature and Bulk-Boundary Correspondence from Transport Measurement for Photonic Chern Bands.

Berry curvature is a fundamental element to characterize topological quantum physics, while a full measurement of Berry curvature in momentum space was not reported for topological states. Here we achieve two-dimensional Berry curvature reconstruction in a photonic quantum anomalous Hall system via Hall transport measurement of a momentum-resolved wave packet. Integrating measured Berry curvature over the two-dimensional Brillouin zone, we obtain Chern numbers corresponding to -1 and 0. Further, we identify bulk-boundary correspondence by measuring topology-linked chiral edge states at the boundary. The full topological characterization of photonic Chern bands from Berry curvature, Chern number, and edge transport measurements enables our photonic system to serve as a versatile platform for further in-depth study of novel topological physics.

Device-Independent Quantum Key Distribution Based on the Mermin-Peres Magic Square Game.

Device-independent quantum key distribution (DIQKD) is information-theoretically secure against adversaries who possess a scalable quantum computer and who have supplied malicious key-establishment systems; however, the DIQKD key rate is currently too low. Consequently, we devise a DIQKD scheme based on the quantum nonlocal Mermin-Peres magic square game: our scheme asymptotically delivers DIQKD against collective attacks, even with noise. Our scheme outperforms DIQKD using the Clauser-Horne-Shimony-Holt game with respect to the number of game rounds, albeit not number of entangled pairs, provided that both state visibility and detection efficiency are high enough.

Room Temperature Synthesis of a Well-Defined Conjugated Polymer Using Direct Arylation Polymerization (DArP).

While a major improvement to the sustainability of conjugated polymer synthesis, traditional direct arylation polymerization (DArP) still requires high temperatures (typically >100 °C), necessitating a significant energy input requirement. Performing DArP at reduced or ambient temperatures would represent an improvement to the sustainability of the reaction. Here we describe the first report of a well-defined conjugated polymer synthesized by DArP at room temperature. Previous efforts toward room temperature DArP relied on the use of a near-stoichiometric silver reagent, an expensive coinage metal, which makes the reaction less cost-effective and sustainable. Here, room temperature polymerizations of 3,4-ethylenedioxythiophene (EDOT) and 9,9-dioctyl-2,7-diiodofluorene were optimized and provided molar mass (Mn) up to 11 kg/mol PEDOTF, and performing the reaction at the standard ambient temperature of 25 °C provided Mn up to 15 kg/mol. Model studies using other C-H monomers of varying electron density copolymerized with 9,9-dioctyl-2,7-diiodofluorene provided insight into the scope of the room temperature polymerization, suggesting that performing room temperature DArP is highly dependent on the electron richness of the C-H monomer.

Observation of dark edge states in parity-time-symmetric quantum dynamics.

Topological edge states arise in non-Hermitian parity-time ([Formula: see text])-symmetric systems, and manifest themselves as bright or dark edge states, depending on the imaginary components of their eigenenergies. As the spatial probabilities of dark edge states are suppressed during the non-unitary dynamics, it is a challenge to observe them experimentally. Here we report the experimental detection of dark edge states in photonic quantum walks with spontaneously broken [Formula: see text] symmetry, thus providing a complete description of the topological phenomena therein. We experimentally confirm that the global Berry phase in [Formula: see text]-symmetric quantum-walk dynamics unambiguously defines topological invariants of the system in both the [Formula: see text]-symmetry-unbroken and -broken regimes. Our results establish a unified framework for characterizing topology in [Formula: see text]-symmetric quantum-walk dynamics, and provide a useful method to observe topological phenomena in [Formula: see text]-symmetric non-Hermitian systems in general.

Waitlist and Transplant Outcomes in Organ Donation After Circulatory Death: Trends in the United States.

OBJECTIVES: To summarize waitlist and transplant outcomes in kidney, liver, lung, and heart transplantation using organ donation after circulatory death (DCD). BACKGROUND: DCD has expanded the donor pool for solid organ transplantation, most recently for heart transplantation. METHODS: The United Network for Organ Sharing registry was used to identify adult transplant candidates and recipients in the most recent allocation policy eras for kidney, liver, lung, and heart transplantation. Transplant candidates and recipients were grouped by acceptance criteria for DCD versus brain-dead donors [donation after brain death (DBD)] only and DCD versus DBD transplant, respectively. Propensity matching and competing-risks regression was used to model waitlist outcomes. Survival was modeled using propensity matching and Kaplan-Meier and Cox regression analysis. RESULTS: DCD transplant volumes have increased significantly across all organs. Liver candidates listed for DCD organs were more likely to undergo transplantation compared with propensity-matched candidates listed for DBD only, and heart and liver transplant candidates listed for DCD were less likely to experience death or clinical deterioration requiring waitlist inactivation. Propensity-matched DCD recipients demonstrated an increased mortality risk up to 5 years after liver and kidney transplantation and up to 3 years after lung transplantation compared with DBD. There was no difference in 1-year mortality between DCD and DBD heart transplantation. CONCLUSIONS: DCD continues to expand access to transplantation and improves waitlist outcomes for liver and heart transplant candidates. Despite an increased risk for mortality with DCD kidney, liver, and lung transplantation, survival with DCD transplant remains acceptable.

Pyroglutamic acidosis caused by the combination of two common medicines prescribed in everyday practice.

We present the case of a 71-year-old female treated for infective endocarditis with flucloxacillin and paracetamol. Her clinical course became complicated by a blood-gas demonstrating a raised anion gap metabolic acidosis. The patient was diagnosed with pyroglutamic metabolic acidosis. This is a rare interaction between high dose flucloxacillin and paracetamol, and is an important complication to recognize.

High-Performance Intrinsically Stretchable Polymer Solar Cell with Record Efficiency and Stretchability Enabled by Thymine-Functionalized Terpolymer.

Designing new polymer semiconductors for intrinsically stretchable polymer solar cells (IS-PSCs) with high power conversion efficiency (PCE) and durability is critical for wearable electronics applications. Nearly all high-performance PSCs are constructed using fully conjugated polymer donors (PD) and small-molecule acceptors (SMA). However, a successful molecular design of PDs for high-performance and mechanically durable IS-PSCs without sacrificing conjugation has not been realized. In this study, we design a novel thymine side chain terminated 6,7-difluoro-quinoxaline (Q-Thy) monomer and synthesize a series of fully conjugated PDs (PM7-Thy5, PM7-Thy10, PM7-Thy20) featuring Q-Thy. The Q-Thy units capable of inducing dimerizable hydrogen bonding enable strong intermolecular PD assembly and highly efficient and mechanically robust PSCs. The PM7-Thy10:SMA blend demonstrates a combination of high PCE (>17%) in rigid devices and excellent stretchability (crack-onset value >13.5%). More importantly, PM7-Thy10-based IS-PSCs show an unprecedented combination of PCE (13.7%) and ultrahigh mechanical durability (maintaining 80% of initial PCE after 43% strain), illustrating the promising potential for commercialization in wearable applications.

Ten-year update: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-42 randomized trial: extended letrozole therapy in early-stage breast cancer.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project B-42 trial evaluated extended letrozole therapy (ELT) in postmenopausal breast cancer patients who were disease free after 5 years of aromatase inhibitor (AI)-based therapy. Seven-year results demonstrated a nonstatistically significant trend in disease-free survival (DFS) in favor of ELT. We present 10-year outcome results. METHODS: In this double-blind, phase III trial, patients with stage I-IIIA hormone receptor-positive breast cancer, disease free after 5 years of an AI or tamoxifen followed by an AI, were randomly assigned to 5 years of letrozole or placebo. Primary endpoint was DFS, defined as time from random assignment to breast cancer recurrence, second primary malignancy, or death. All statistical tests are 2-sided. RESULTS: Between September 2006 and January 2010, 3966 patients were randomly assigned (letrozole: 1983; placebo: 1983). Median follow-up time for 3923 patients included in efficacy analyses was 10.3 years. There was statistically significant improvement in DFS in favor of letrozole compared with placebo (hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.74 to 0.96; P = .01; 10-year DFS: placebo = 72.6%, letrozole = 75.9%, absolute difference = 3.3%). There was no difference in the effect of letrozole on overall survival (HR = 0.97, 95% CI = 0.82 to 1.15; P = .74). Letrozole statistically significantly reduced breast cancer-free interval events (HR = 0.75, 95% CI = 0.62 to 0.91; P = .003; absolute difference in cumulative incidence = 2.7%) and distant recurrences (HR = 0.72, 95% CI = 0.55 to 0.92; P = .01; absolute difference = 1.8%). The rates of osteoporotic fractures and arterial thrombotic events did not differ between treatment groups. CONCLUSIONS: The beneficial effect of ELT on DFS persisted at 10 years. Letrozole also improved breast cancer-free interval and distant recurrences without improving overall survival. Careful assessment of potential risks and benefits is necessary for selecting appropriate candidates for ELT.