Nanosized DNA Hydrogel Functionalized with a DNAzyme Tetrahedron for Highly Efficient Gene Silencing.

DNAzymes are DNA oligonucleotides that have catalytic activity without the assistance of protein enzymes. In particular, RNA-cleaving DNAzymes were considered as ideal candidates for gene therapy due to their unique characteristics. Nevertheless, efforts to use DNAzyme as a gene therapeutic agent are limited by issues such as their low physiological stability in serum and intracellular delivery efficiency. In this study, we developed a nanosized synthetic DNA hydrogel functionalized with a DNAzyme tetrahedron (TDz Dgel) to overcome these limitations. We observed remarkable improvement in the gene-silencing effect as well as intracellular uptake without the support of gene transfection reagents using TDz Dgel. The improved catalytic activity of the DNAzyme resulted from the combination of the cell-penetrating DNA tetrahedron structure and high stability of DNA hydrogel. We envision that this approach will become a convenient and efficient strategy for gene-silencing therapy using DNAzyme in the future.

Oxidative and carbonyl stress induced AMD and Codonopsis lanceolata ameliorates AMD via controlling oxidative and carbonyl stress.

Age-related macular degeneration (AMD) is one of the leading causes of blindness. AMD is currently incurable; the best solution is to prevent its occurrence. To develop drugs for AMD, it is crucial to have a model system that mimics the symptoms and mechanisms in patients. It is most important to develop safer and more effective anti-AMD drug. In this study, the dose of A2E and the intensity of blue light were evaluated to establish an appropriate atrophic in vitro model of AMD and anti-AMD effect and therapeutic mechanism of Codonopsis lanceolata. The experimental groups included a control group an AMD group treated with A2E and blue light, a lutein group treated with 25 µM lutein after AMD induction, and three groups treated with different doses of C. lanceolata (10, 20, and 50 µg/mL) after AMD induction. Intrinsic apoptotic pathway (Bcl-2 family), anti-oxidative system (Keap1/Nrf2/HO-1 antioxidant response element), and anti-carbonyl effect (4-hydroxynonenal [4-HNE]) were evaluated using immunofluorescence, MTT, TUNEL, FACS, and western blotting analyses. A2E accumulation in the cytoplasm of ARPE-19 cells depending on the dose of A2E. Cell viability of ARPE-19 cells according to the dose of A2E and/or blue light intensity. The population of apoptotic or necrotic cells increased based on the A2E dose and blue light intensity. Codonopsis lanceolata dose-dependently prevented cell death which was induced by A2E and blue light. The antiapoptotic effect of that was caused by activating Keap1/Nrf2/HO-1 pathway, suppressing 4-HNE, and modulating Bcl-2 family proteins like increase of antiapoptotic proteins such as Bcl-2 and Bcl-XL and decrease of proapoptotic protein such as Bim. Based on these findings, 30 µM A2E and 20 mW/cm2 blue light on adult retinal pigment epithelium-19 cells was an appropriate condition for AMD model and C. lanceolata shows promise as an anti-AMD agent.

Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial.

BACKGROUND: Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis. METHODS: Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the proportion of time covered (PTC) by screening. All patients were included in intention-to-screen analyses. RESULTS: All 2872 participants (median age 61.3 years; 32.3% women) were included in intention-to-screen analyses. Screening process completion was observed in 6.6% (95% CI: 5.3% to 7.9%) of patients randomised to outreach and 3.3% (95% CI: 2.4% to 4.3%) of those randomised to usual care (OR 2.05, 95% CI: 1.44 to 2.92). The intervention increased HCC screening process completion across most subgroups including age, sex, race and ethnicity, Child-Turcotte-Pugh class and health system. PTC was also significantly higher in the outreach arm than usual care (mean 37.5% vs 28.2%; RR 1.33, 95% CI: 1.31 to 1.35). Despite screening underuse, most HCC in both arms were detected at an early stage. CONCLUSION: Mailed outreach plus navigation significantly increased HCC screening process completion versus usual care in patients with cirrhosis, with a consistent effect across most examined subgroups. However, screening completion remained suboptimal in both arms, underscoring a need for more intensive interventions. TRIAL REGISTRATION NUMBER: NCT02582918.

Sex Differences Persist After Treatment With Ivacaftor in People With Cystic Fibrosis.

BACKGROUND: Historically, studies show that female patients with cystic fibrosis (CF) have worse pulmonary outcomes than male patients, including decreased life expectancy. It is unknown whether this disparity persists in the new era of highly effective modulator therapies. Ivacaftor has been available in the United States for > 10 years, allowing for the opportunity to understand the impact this therapy may have on sex disparities in CF. We hypothesized that female patients will continue to show worse outcomes because we suspect that the disparity is not driven solely by ion channel dysfunction. RESEARCH QUESTION: Does a difference in outcomes between male and female patients persist after the initiation of ivacaftor in people with CF? STUDY DESIGN AND METHODS: We conducted a retrospective cohort study using the CF Foundation Patient Registry comparing changes in pulmonary exacerbation rate, lung function (FEV1 % predicted), and presence of Pseudomonas aeruginosa among male patients vs female patients before and after initiation of treatment with the highly effective modulator ivacaftor. RESULTS: The cohort comprised 1,900 people with CF who were treated with ivacaftor between 2010 and 2017; 928 patients (48.84%) were male and 972 patients (51.16%) were female with a mean age of 33.09 years. Male patients showed a significant decrease in pulmonary exacerbations after ivacaftor treatment (from 0.38 to 0.34; adjusted rate ratio, 0.89; P = .028), whereas female patients did not (from 0.48 to 0.45; adjusted rate ratio, 0.95; P = .174). FEV1 % predicted similarly decreased in both male and female patients before vs after ivacaftor treatment. P aeruginosa prevalence decreased to a similar extent in both male and female patients after ivacaftor treatment. INTERPRETATION: Our findings demonstrate that sex disparities in CF persist in those treated with ivacaftor because of differences in pulmonary exacerbations. More research is needed to determine the specific pathophysiologic drivers of this disparity.

Concentrations of dehydroepiandrosterone-sulphate (DHEA-S) in people with cystic fibrosis on and off elexacaftor-tezacaftor-ivacaftor.

BACKGROUND: Levels of sulfated Dehydroepiandrosterone (DHEA-S) are unknown in people with Cystic Fibrosis (pwCF). DHEA-S is reported to have an inverse association with inflammation and warrants evaluation in pwCF. METHODS: We compared differences in DHEA-S and other hormones between pwCF (n = 180) and without CF (n = 180) and DHEA-S association with percent predicted forced expiratory volume in one second (ppFEV1). We also evaluated DHEA-S levels in people with CF on elexacaftor-tezacaftor-ivacaftor (ETI) (n = 145). RESULTS: PwCF (not on ETI) had lower DHEA-S levels compared to healthy non-CF controls. DHEA-S levels in individuals with CF on ETI were similar to those without CF. Lower DHEA-S levels were associated with lower ppFEV1. CONCLUSIONS: PwCF (not on ETI) have lower levels of DHEA-S than people without CF or people with CF on ETI. Additional studies are needed to investigate the impact of DHEA-S on the health of pwCF and mechanisms involved.

Beyond the Diagnosis: Evaluation of Quality-of-Life Measures and Family Functioning in SLC6A1-Related Neurodevelopmental Disorder.

BACKGROUND: SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD) is a rare genetic disorder linked to autism spectrum disorder, epilepsy, and developmental delay. In preparation for future clinical trials, understanding how the disorder impacts patients and their families is critically important. Quality-of-life (QoL) measures capture the overall disease experience of patients. This study presents QOL findings from our SLC6A1-NDD clinical trial readiness study and the Simons Searchlight SLC6A1-NDD registry. METHODS: We compiled QoL data from participants with SLC6A1-NDD enrolled in our clinical trial readiness study (n = 20) and the Simons Searchlight registry (n = 32). We assessed the distribution of scores on the Quality-of-Life Inventory-Disability (QI Disability), Quality of Life of Childhood Epilepsy (QOLCE-55), and Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM) administered to caregivers. RESULTS: In our cohort of 52 participants, the mean QI Disability total score was 73 ± 12.3, the QOLCE-55 mean total score was 49 ± 17.1, and the mean total PedsQL score was 51 ± 17.6. Longitudinal QoL scores for a subset of participants (n = 7) demonstrated a reduction in the Family Relationship domain of PedsQL-FIM (Δ-10.0, P = 0.035). Bootstrap resampling of total scores displays nonoverlapping 95% confidence intervals for the 10th, 50th, and 90th percentiles on all three measures. CONCLUSIONS: This is the first study to investigate QoL measures for SLC6A1-NDD. Findings suggest that scores within the 10th percentile's confidence interval could be clinically significant, referring to QI-Disability scores of <61, QOLCE-55 scores of <46, and PedsQL-FIM scores of <42. Future validation studies are needed.

An expanded chronic care management approach to multiple chronic conditions in Hispanics using community health workers as community extenders in the Rio Grande Valley of Texas.

INTRODUCTION: The synergistic negative effects of type 2 diabetes (T2DM) and hypertension increases all-cause mortality and the medical complexity of management, which disproportionately impact Hispanics who face barriers to healthcare access. The Salud y Vida intervention was delivered to Hispanic adults living along the Texas-Mexico Border with comorbid poorly controlled T2DM and hypertension. The Salud y Vida multicomponent intervention incorporated community health workers (CHWs) into an expanded chronic care management model to deliver home-based follow-up visits and provided community-based diabetes self-management education. METHODS: We conducted multivariable longitudinal analysis to examine the longitudinal intervention effect on reducing systolic and diastolic blood pressure among 3806 participants enrolled between 2013 and 2019. Participants were compared according to their program participation as either higher (≥ 10 combined educational classes and CHW visits) or lower engagement (<10 encounters). Data was collected between 2013 and 2020. RESULTS: Baseline mean systolic and diastolic blood pressure were 138 and 81 mmHg respectively. There were overall improvements in systolic (-6.49; 95% CI = [-7.13, -5.85]; p < 0.001) and diastolic blood pressure (-3.97; 95% CI = [-4.37, -3.56]; p < 0.001). The higher engagement group had greater systolic blood pressure reduction at 3 months (adjusted mean difference = -1.8 mmHg; 95% CI = [-3.2, -0.3]; p = 0.016) and at 15 month follow-up (adjusted mean difference = -2.3 mmHg; 95% CI = [-4.2, -0.39]; p = 0.0225) compared to the lower engagement group. CONCLUSION: This intervention, tested and delivered in a real-world setting, provides an example of how CHW integration into an expanded chronic care model can improve blood pressure outcomes for individuals with co-morbidities.

Dynamic Hyperspectral Holography Enabled by Inverse-Designed Metasurfaces with Oblique Helicoidal Cholesterics.

Metasurfaces are flat arrays of nanostructures that allow exquisite control of phase and amplitude of incident light. Although metasurfaces offer new active element for both fundamental science and applications, the challenge still remains to overcome their low information capacity and passive nature. Here, by integrating an inverse-designed-metasurface with oblique helicoidal cholesteric liquid crystal (ChOH), simultaneous spatial and spectral tunable metasurfaces with a high information capacity for dynamic hyperspectral holography, are demonstrated. The inverse design facilitates a single-phase map encoding of ten independent holographic images at different wavelengths. ChOH provides precise spectral modulation with narrow bandwidth and wide tunable regime in response to programmed stimuli, thus enabling dynamic switching of the multicolor holography. The results provide simple and generalizable principles for the rational design of interactive metasurfaces that will find numerous applications, including security platform.

Risk of Obstructive Sleep Apnea, Chronic Dizziness, and Sleep Duration.

BACKGROUND: Although it is recommended that obstructive sleep apnea (OSA) be screened for using a validated self-report questionnaire in patients experiencing dizziness, there is still a lack of research on the relationship between high risk of OSA and chronic dizziness. OBJECTIVES: The study aimed to examine the relationship between the high risk of OSA and chronic dizziness and investigate how this relationship is affected by sleep duration. METHODS: This cross-sectional study used data from the 8th Korea National Health and Nutrition Examination Survey (2019-2021). Adults aged 40 years or older were included and divided into two groups using the STOP-Bang Questionnaire (SBQ): a high-risk group for OSA or not. Complex samples logistic regression analyses were performed to examine the odds ratios of chronic dizziness based on the national population estimates. RESULTS: Our findings showed that individuals in the high-risk group for OSA were significantly more likely to experience chronic dizziness. Specifically, among subgroups based on sleep duration, the high-risk group for OSA with a short sleep duration of ≤5 hours demonstrated the highest odds of chronic dizziness, showing a significantly 2.48-fold increased likelihood compared to the non-high risk for OSA with a sleep duration of 5-9 hours. DISCUSSION: The SBQ can be beneficial when other causes do not explain chronic dizziness, helping to rule in the possibility of OSA. Educating individuals suspected of having OSA or who have been diagnosed with OSA about the importance of adequate sleep duration may help reduce the risk of chronic dizziness.

Association of in-line digestive enzyme cartridge with enteral feeds on improvement in anthropometrics among pediatric patients with cystic fibrosis.

BACKGROUND: Approximately 85% of patients with cystic fibrosis (CF) have exocrine pancreatic insufficiency (EPI) with 10% requiring supplemental nighttime enteral tube feedings. Administration of pancreatic enzyme replacement therapy (PERT) with nighttime feedings is fraught with challenges. RELiZORB (Alcresta Therapeutics, Inc), an in-line lipase cartridge, delivers PERT continuously with enteral feedings. Outcomes related to the use of this in-line lipase cartridge are lesser known. This project evaluated anthropometrics related to in-line lipase cartridge use among pediatric patients with CF already receiving oral PERT therapy prior to nighttime enteral feedings. METHODS: Retrospective chart review was performed on 29 patients with CF and EPI receiving supplemental tube feedings and utilizing in-line lipase cartridge for a continuous 12 month period between 2015 and 2019. Anthropometrics were evaluated 12 months before and after initiation of in-line lipase cartridge. RESULTS: Compared with mean height z score at 6-months pre-in-line lipase cartridge, mean height z score at 6-months post-in-line-lipase cartridge (adjusted mean difference [AMD] = 0.2540; 95% CI = [0.0487, 0.4592]; P = 0.0153) and mean height z score at 12-months post-in-line lipase cartridge (AMD = 0.2684; 95% CI = [0.0203, 0.5166]; P = 0.0340) were significantly higher. Mean weight z score at 12-months post-in-line-lipase-cartridge neared statistical significance compared with 6-months pre-in-line lipase cartridge (AMD = 0.2816; 95% CI = [-0.0003, 0.5634]; P = 0.0502) when excluding seven patients with advanced lung disease (forced expiratory volume in the first second of expiration of 40%). Weight-for-length or body mass index did not significantly differ compared with pre-in-line lipase cartridge. CONCLUSION: Use of in-line lipase cartridge with enteral feeds improved anthropometrics, especially height, in pediatric patients with CF.

Associations of Ambulatory Blood Pressure Measurements With High-Sensitivity Troponin and Natriuretic Peptide Levels in SPRINT.

BACKGROUND: Nighttime blood pressure (BP) has greater prognostic importance for cardiovascular disease (CVD) than daytime BP, but less is known about nighttime and daytime BP associations with measures of subclinical CVD. METHODS: Among 897 Systolic Blood Pressure Intervention Trial Study (SPRINT) participants with 24-hour ambulatory BP monitoring obtained near the 27-month study visit, 849 (95%) had N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) measured at the 24-month study visit. Multivariable linear regression analyses were performed to evaluate the associations of nighttime and daytime BP with cardiac biomarker levels. RESULTS: The mean age was 69 ±â€…12 years, 28% were African American, and mean nighttime and daytime SBP were 121 ±â€…16 mm Hg and 132 ±â€…14 mm Hg, respectively. In multivariable models, compared with the lowest tertile of nighttime systolic BP, the highest tertile was associated with 48% higher NT-proBNP levels (adjusted geometric mean ratio [GMR] = 1.48, 95% CI: 1.22, 1.79), and 19% higher hs-cTnT levels (adjusted GMR = 1.19, 95% CI: 1.07, 1.32). In contrast, the highest vs. lowest tertile of daytime systolic BP was not associated with NT-proBNP (adjusted GMR = 1.09, 95% CI: 0.88, 1.34), but was associated with 16% higher hs-cTnT levels (adjusted GMR = 1.16, 95% CI: 1.04, 1.30). Similar results were observed using diastolic BP. CONCLUSIONS: In SPRINT, both higher nighttime and daytime BP were independently associated with higher hs-cTnT levels, but only higher nighttime BP was associated with higher NT-proBNP levels.

Intramedullary Positive Tissue Culture Increases the Risk of Reinfection Following One-Stage Septic Revision Total Knee Arthroplasty.

BACKGROUND: Intraoperative acquisition of representative tissue samples is essential during revision arthroplasty of the infected total knee arthroplasty (TKA). While the number of intraoperative tissue samples needed to identify the organism is well described in the literature, there is still a paucity of evidence regarding the location of positive intraoperative samples and their correlation to postoperative outcomes. METHODS: There were forty-two patients who had septic failure following one-stage revision TKA for periprosthetic joint infection who were identified between January 2009 and December 2017. They were matched to a control group of patients who had successful one-stage revision TKA without septic failure. The location of positive intraoperative tissue samples was categorized as: 1) soft tissue; 2) interface between bone and prosthesis; and 3) intramedullary (IM). Chi-square, Student's t-, and Wilcoxon Mann-Whitney U-tests were used as appropriate. Univariate and multivariate logistic regression analyses were performed to evaluate predictors of septic failure. RESULTS: Weight > 100 kilograms (P = .033), higher Charlson Comorbidity Index (P < .001), and positive IM cultures (P < .001) were associated with a higher risk of reinfection after one-stage revision TKA. A positive IM sample carried a nearly five-fold increase in odds of reinfection (odds ratio 4.86, 95% confidence interval 1.85 to 12.78, P = .001). CONCLUSIONS: A positive IM culture sample is significantly associated with septic failure after one-stage exchange for periprosthetic joint infection of the knee. Patients who had positive IM cultures may benefit from longer postoperative antibiotic therapy for the treatment of one-stage exchange arthroplasty to minimize the risk of reinfection.

Framework for dual-energy-like chest radiography image synthesis from single-energy computed tomography based on cycle-consistent generative adversarial network.

BACKGROUND: Dual-energy (DE) chest radiography (CXR) enables the selective imaging of two relevant materials, namely, soft tissue and bone structures, to better characterize various chest pathologies (i.e., lung nodule, bony lesions, etc.) and potentially improve CXR-based diagnosis. Recently, deep-learning-based image synthesis techniques have attracted considerable attention as alternatives to existing DE methods (i.e., dual-exposure-based and sandwich-detector-based methods) because software-based bone-only and bone-suppression images in CXR could be useful. PURPOSE: The objective of this study was to develop a new framework for DE-like CXR image synthesis from single-energy computed tomography (CT) based on a cycle-consistent generative adversarial network. METHODS: The core techniques of the proposed framework are divided into three categories: (1) data configuration from the generation of pseudo CXR from single energy CT, (2) learning of the developed network architecture using pseudo CXR and pseudo-DE imaging using a single-energy CT, and (3) inference of the trained network on real single-energy CXR. We performed a visual inspection and comparative evaluation using various metrics and introduced a figure of image quality (FIQ) to consider the effects of our framework on the spatial resolution and noise in terms of a single index through various test cases. RESULTS: Our results indicate that the proposed framework is effective and exhibits potential synthetic imaging ability for two relevant materials: soft tissue and bone structures. Its effectiveness was validated, and its ability to overcome the limitations associated with DE imaging techniques (e.g., increase in exposure dose owing to the requirement of two acquisitions, and emphasis on noise characteristics) via an artificial intelligence technique was presented. CONCLUSIONS: The developed framework addresses X-ray dose issues in the field of radiation imaging and enables pseudo-DE imaging with single exposure.

Financial Burden of Hepatocellular Carcinoma Screening in Patients With Cirrhosis.

BACKGROUND: The overall value of hepatocellular carcinoma screening is defined by the balance of benefits and harms. Studies have only reported physical harms with none describing financial harms. METHODS: We conducted a multicenter pragmatic randomized clinical trial of hepatocellular carcinoma screening outreach among 2872 patients with cirrhosis from March 2018 to April 2021. Patients with positive or indeterminate results and matched patients with negative results completed surveys at baseline and at follow-up measuring financial harms via Cancer Self-Administered Questionnaire and financial burden via Comprehensive Score for Financial Toxicity Functional Assessment of Chronic Illness Therapy. Univariable and multivariable longitudinal regression analyses were performed to compare changes in financial harms across groups: true positive, true negative, false positive, and indeterminate. Semistructured interviews were conducted in a subset of patients, sampled by center and test result. RESULTS: Of 311 patients who completed at least 1 follow-up survey (75% response rate), 37 had true positive, 133 true negative, 64 false positive, and 77 indeterminate results. Financial harms increased in true positive and false positive patients with no significant changes noted among those with true negative or indeterminate results. At follow-up, 21.8% of patients reported moderate-severe financial burden, which was not significantly associated with test results. Semistructured interviews revealed variation in the frequency and severity of financial harms based on test results, with increased harm in those with false positive results. CONCLUSIONS: Financial harms of hepatocellular carcinoma screening vary by test result and can pose a barrier that must be considered when determining the optimal screening program.

Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis.

BACKGROUND AND AIMS: The value of HCC surveillance is determined by the balance between benefits and harms; however, no studies have enumerated psychological harms. APPROACH AND RESULTS: We fielded surveys measuring psychological harms to patients with cirrhosis in a multicenter randomized trial of HCC surveillance outreach. All patients with positive or indeterminate surveillance results and matched patients with negative results were invited to complete surveys measuring (1) depression through the Patient Health Questionnaire-ninth version, (2) anxiety through State-Trait Anxiety Inventory, (3) HCC-specific worry through Psychological Consequences Questionnaire, and (4) decisional regret. Patients were classified into 4 groups: true positive (TP), false positive (FP), indeterminate, and true negative (TN). Multivariable longitudinal regression analysis using the generalized estimating equation method was performed to compare the means of measures across groups. We conducted 89 semistructured interviews in a subset of patients stratified by health system and test results. Of 2872 patients in the trial, 311 completed 1+ follow-up survey (63 FP, 77 indeterminate, 38 TP, and 133 TN). Moderate depression decreased in TN patients, increased in TP, and had intermittent but mild increases in those with FP and indeterminate results. High anxiety temporarily increased in patients with TP results but resolved over time and was stable in those with FP and indeterminate results. Decisional regret was low and did not differ across groups. In semistructured interviews, patients reported apprehension, anxiety, emotional distress, and coping related to HCC surveillance. CONCLUSIONS: Psychological harms of HCC surveillance appear mild but differ by test result. Future research should determine the impact of psychological harms on the value of HCC surveillance programs.

Sex differences in outcomes of people with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: There is a well described sex-disparity in outcomes of individuals with cystic fibrosis (CF), with females faring worse than males. Given the dramatic improvement in overall health of people with CF using CF transmembrane conductance regulator (CFTR) modulator therapy, elexacaftor/tezacaftor/ivacaftor (ETI), the sex-disparity in CF warrants re-examination. METHODS: We evaluated the effects of ETI use by sex prior to versus after initiation of ETI by pulmonary exacerbations (PEx), percent predicted forced expiratory volume in one second (ppFEV1), presence of Pseudomonas aeruginosa in sputum cultures, and body mass index (BMI). We used univariate and multivariable longitudinal regression adjusting for key confounders, such as age, race, CFTR modulator taken prior to ETI and baseline ppFEV1. RESULTS: We included 251 individuals started on ETI between January 2014 to September 2022. We collected data for a mean of 5.45 years pre-ETI and 2.38 years post-ETI. We found the adjusted presence of PEx decreased more in males than females pre- to post-ETI with the odds of having a PEx in males being 0.57 (43% reduction) versus females 0.75 (25% reduction) (p = 0.049). We found no statistical difference by sex for ppFEV1, presence of Pseudomonas aeruginosa or BMI pre- to post-ETI by sex. CONCLUSION: After treatment with ETI, there was a greater decline in PEx in males versus females. Long-term impact of ETI by sex is still unknown, but we will need to seek ways to effectively tailor care for individuals with CF and consider pharmacokinetic studies of ETI comparing males to females.

Thermophysical properties and bonding with composite resin of premixed mineral trioxide aggregate for use as base material.

Dental bases require low thermal conductivity and good mechanical properties, such as bonding with composite resins. This study aims to elucidate the physicochemical properties of premixed mineral trioxide aggregate (MTA) for its suitability as a dental base and to explore the optimal adhesive strategy with composite resin. The thermal conductivity and compressive strength of this premixed MTA are 0.12 W/(m•K) and 93.76 MPa, respectively, Which are deemed adequate for its application as dental base. When bonded to composite resin, the use of 37% phosphoric acid etching before applying the Clearfil SE bond significantly reduced the bonding strength between composite resin and premixed MTA. This was because the compressive strength and Vickers hardness of premixed MTA decreased, and tricalcium silicate was dissolved from the surface during acid etching. Therefore, it is recommended to avoid using 37% phosphoric acid etching when bonding premixed MTA and composite resin as a dental base.

Accelerated Single Li-Ion Transport in Solid Electrolytes for Lithium-Sulfur Batteries: Poly(Arylene Ether Sulfone) Grafted with Pyrrolidinium-Terminated Poly(Ethylene Glycol).

Polymeric solid electrolytes have attracted tremendous interest in high-safety and high-energy capacity lithium-sulfur (Li─S) batteries. There is, however, still a dilemma to concurrently attain high Li-ion conductivity and high mechanical strength that effectively suppress the Li-dendrite growth. Accordingly, a rapidly Li-ion conducting solid electrolyte is prepared by grafting pyrrolidinium cation (PYR+)-functionalized poly(ethylene glycol) onto the poly(arylene ether sulfone) backbone (PAES-g-2PEGPYR). The PYR+ groups effectively immobilize anions of Li-salts in Li-conductive PEGPYR domains phase-separated from PAES matrix to enhance the single-ion conduction. The tailored PAES-g-2PEGPYR membrane shows a high Li-ion transference number of 0.601 and superior ionic conductivity of 1.38 mS cm-1 in the flexible solid state with the tensile strength of 1.0 MPa and Young's modulus of 1.5 MPa. Moreover, this PAES-g-2PEGPYR membrane exhibits a high oxidation potential (5.5 V) and high thermal stability up to 200 (C. The Li/PAES-g-2PEGPYR/Li cell stably operates for 1000 h without any short circuit, and the rechargeable Li/PAES-g-2PEGPYR/S cell discharges a capacity of 1004.7 mAh g-1 at C/5 with the excellent rate capability and the prominent cycling performance of 95.3% retention after 200 cycles.

Quantification of collagen content and stromal cellularity within reactive stroma is predictive of prostate cancer biochemical recurrence and specific death.

Semiquantitative reactive stromal grading has been shown to be a predictor of biochemical recurrence and prostate cancer (PCa) specific death. It has been extensively validated. In this study we tested novel technologies to introduce quantitative measures of host response, in particular collagen content and stromal cellularity. We use 3 large retrospective cohorts, the Baylor College of Medicine cohort, the Brady cohort and the Pound cohort. Slides were stained and digitized using image deconvolution and analyzed using image segmentation and image analyses. PicroSirius red stain histochemical stains were used for collagen quantification. Area of cancer and stroma were measured independently, without regard to quality of stroma. Cellularity, in each compartment, was measured using image deconvolution, image segmentation and image analysis. Two biomarkers were tested in 3 independent cohorts with two endpoints, biochemical recurrence and prostate cancer specific death. Stromal cellularity (qCollCell) and stromal collagen area (qCollArea) are independently predictive biochemical recurrence in the Hopkins Brady cohort, particularly in Gleason 6-7 patients. Multivariate analysis demonstrated that increased stroma cellularity (qCollCell) was a significant predictor of PCa specific death, when compared to an established model of PCa, in the Baylor cohort. Stromal collagen (qCollArea) independently predicts PCa-specific death in the Hopkins Pound cohort. The introduction of a computerized quantitative test of the host response increases the probability that this test will be reproducible in other cohorts. The ability to improve prediction of prostate cancer specific death might lie in the study of the host and its response.

Tunable Radiative Cooling by Mechanochromic Electrospun Micro-Nanofiber Matrix.

Radiative thermoregulation has been regarded as an energy-efficient method for thermal management. In this study, the development of a mechanoresponsive polydimethylsiloxane (PDMS) micro-nanofiber matrix capable of both sub-ambient radiative cooling and solar heating is presented, achieved through a core-shell electrospinning technique. The electrospun PDMS micro-nanofibers, with diameters comparable to the solar wavelengths, exhibit excellent solar reflectivity (≈93%) while preserving its pristine high infrared (IR) emissivity. As a result, the electrospun PDMS radiative cooler (EPRC) successfully demonstrated sub-ambient radiative cooling performance (≈3.8°C) during the daytime. Furthermore, the exceptional resilient property of PDMS facilitated the reversible alteration of the structural morphology created by the fiber-based matrix under mechanical force, resulting in the modulation of solar reflectivity (≈80%). The precise modulation of solar reflectivity enabled reversibly switchable multi-step radiative thermoregulation, offering enhanced flexibility in addressing varying thermal environments even in maintaining the desired temperature. The findings of this work offer a promising approach toward dynamic radiative thermoregulation, which holds significant potential for addressing global climate change concerns and energy shortage.