Designing macroscopic, 3D porous conductive materials with high mechanical strength is of great importance in many fields, including energy storage, catalysis, etc. This study reports a novel ...approach to fabricate polyaniline‐coated 3D carbon x‐aerogels, a special type of aerogels with mechanically strong, highly cross‐linked structure that allows the originally brittle aerogels machinable. This approach is accomplished by introducing a small amount of graphene into the sol–gel process of resorcinol and formaldehyde, followed by physical activation and subsequent cross‐linking with polyaniline via electropolymerization. The resulting x‐aerogels are not only porous and conductive, but also mechanically robust with high compressibility and fast recovery. The strong combination of these properties makes the x‐aerogels promising for high performance supercapacitors that are designed to provide additional functionality for wearable and portable electronics. Such multi‐functionality leads to a significant increase in electrochemical performance, in particular high volumetric capacitance, which results from the more densely packed electroactive structure in three dimensions. More importantly, monoliths of carbon x‐aerogels are machinable into thin slices without losing their properties, thus enabling effective integration into devices with different sizes and shapes.
Strong, machinable carbon aerogels are reported, developed to be not only porous and conductive, but also mechanically robust with high compressibility and fast recovery. The synergistic combination of these properties makes the aerogels promising for high performance supercapacitors that are designed to provide additional functionality for wearable and portable electronics.
Recurrent gene fusions, such as ROS1 fusions, are oncogenic drivers of various cancers, including non-small-cell lung cancer (NSCLC). Up to 36% of patients with ROS1 fusion-positive NSCLC have brain ...metastases at the diagnosis of advanced disease. Entrectinib is a ROS1 inhibitor that has been designed to effectively penetrate and remain in the CNS. We explored the use of entrectinib in patients with locally advanced or metastatic ROS1 fusion-positive NSCLC.
We did an integrated analysis of three ongoing phase 1 or 2 trials of entrectinib (ALKA-372-001, STARTRK-1, and STARTRK-2). The efficacy-evaluable population included adult patients (aged ≥18 years) with locally advanced or metastatic ROS1 fusion-positive NSCLC who received entrectinib at a dose of at least 600 mg orally once per day, with at least 12 months' follow-up. All patients had an Eastern Cooperative Oncology Group performance status of 0–2, and previous cancer treatment (except for ROS1 inhibitors) was allowed. The primary endpoints were the proportion of patients with an objective response (complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1) and duration of response, and were evaluated by blinded independent central review. The safety-evaluable population for the safety analysis included all patients with ROS1 fusion-positive NSCLC in the three trials who received at least one dose of entrectinib (irrespective of dose or duration of follow-up). These ongoing studies are registered with ClinicalTrials.gov, NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012–000148–88 (ALKA-372-001).
Patients were enrolled in ALKA-372-001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018), 41 (77%; 95% CI 64–88) of 53 patients in the efficacy-evaluable population had an objective response. Median follow-up was 15·5 monhts (IQR 13·4–20·2). Median duration of response was 24·6 months (95% CI 11·4–34·8). In the safety-evaluable population, 79 (59%) of 134 patients had grade 1 or 2 treatment-related adverse events. 46 (34%) of 134 patients had grade 3 or 4 treatment-related adverse events, with the most common being weight increase (ten 8%) and neutropenia (five 4%). 15 (11%) patients had serious treatment-related adverse events, the most common of which were nervous system disorders (four 3%) and cardiac disorders (three 2%). No treatment-related deaths occurred.
Entrectinib is active with durable disease control in patients with ROS1 fusion-positive NSCLC, and is well tolerated with a manageable safety profile, making it amenable to long-term dosing in these patients. These data highlight the need to routinely test for ROS1 fusions to broaden therapeutic options for patients with ROS1 fusion-positive NSCLC.
Ignyta/F Hoffmann-La Roche.
Background & Aims Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced ...remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial. Methods We performed a parallel study of patients with active UC without infectious diarrhea. Participants were examined by flexible sigmoidoscopy when the study began and then were randomly assigned to groups that received FMT (50 mL, via enema, from healthy anonymous donors; n = 38) or placebo (50 mL water enema; n = 37) once weekly for 6 weeks. Patients, clinicians, and investigators were blinded to the groups. The primary outcome was remission of UC, defined as a Mayo score ≤2 with an endoscopic Mayo score of 0, at week 7. Patients provided stool samples when the study began and during each week of FMT for microbiome analysis. The trial was stopped early for futility by the Data Monitoring and Safety Committee, but all patients already enrolled in the trial were allowed to complete the study. Results Seventy patients completed the trial (3 dropped out from the placebo group and 2 from the FMT group). Nine patients who received FMT (24%) and 2 who received placebo (5%) were in remission at 7 weeks (a statistically significant difference in risk of 17%; 95% confidence interval, 2%−33%). There was no significant difference in adverse events between groups. Seven of the 9 patients in remission after FMT received fecal material from a single donor. Three of the 4 patients with UC ≤1 year entered remission, compared with 6 of 34 of those with UC >1 year ( P = .04, Fisher’s exact test). Stool from patients receiving FMT had greater microbial diversity, compared with baseline, than that of patients given the placebo ( P = .02, Mann-Whitney U test). Conclusions FMT induces remission in a significantly greater percentage of patients with active UC than placebo, with no difference in adverse events. Fecal donor and time of UC appear to affect outcomes. ClinicalTrials.gov Number: NCT01545908.
We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The number of ...pan-genes in these diverse genomes exceeds 103,000, with approximately a third found across all genotypes. The results demonstrate that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres revealed additional variation in major cytological landmarks. We show that combining structural variation with single-nucleotide polymorphisms can improve the power of quantitative mapping studies. We also document variation at the level of DNA methylation and demonstrate that unmethylated regions are enriched for cis-regulatory elements that contribute to phenotypic variation.
A "top-down" and scalable approach for processing carbon fiber cloth (CFC) into flexible and all-carbon electrodes with remarkable areal capacity and cyclic stability was developed. CFC is ...commercially available in large quantities but its use as an electrode material in supercapacitors is not satisfactory. The approach demonstrated in this work is based on the sequential treatment of CFC with KOH activation and high temperature annealing that can effectively improve its specific surface area to a remarkable 2780 m(2) g(-1) while at the same time achieving a good electrical conductivity of 320 S m(-1) without sacrificing its intrinsic mechanical strength and flexibility. The processed CFC can be directly used as an electrode for supercapacitors without any binders, conductive additives and current collectors while avoiding elaborate electrode processing steps to deliver a specific capacitance of ∼0.5 F cm(-2) and ∼197 F g(-1) with remarkable rate performance and excellent cyclic stability. The properties of these processed CFCs are comparable or better than graphene and carbon nanotube based electrodes. We further demonstrate symmetric solid-state supercapacitors based on these processed CFCs with very good flexibility. This "top-down" and scalable approach can be readily applied to other types of commercially available carbon materials and therefore can have a substantial significance for high performance supercapacitor devices.
IMPORTANCE: Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated ...clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention. OBJECTIVE: To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada. INTERVENTIONS: Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema. MAIN OUTCOMES AND MEASURES: The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%. RESULTS: A total of 219 patients (n = 108 in the frozen FMT group and n = 111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n = 91, fresh FMT: n = 87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, −1.6% 95% CI, –10.5% to ∞; P = .01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% 95% CI, –5.2% to ∞; P < .001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups. CONCLUSIONS AND RELEVANCE: Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01398969
Abstract Objective To determine the false-negative rate of a surgical sentinel lymph node (SLN) mapping algorithm that incorporates more than just removing SLNs in detecting metastatic endometrial ...cancer. Methods A prospective database of all patients who underwent lymphatic mapping for endometrial cancer was reviewed. Cervical injection of blue dye was used in all cases. The surgical algorithm is as follows: 1) peritoneal and serosal evaluation and washings; 2) retroperitoneal evaluation including excision of all mapped SLNs and suspicious nodes regardless of mapping; and 3) if there is no mapping on a hemi-pelvis, a side-specific pelvic, common iliac, and interiliac lymph node dissection (LND) is performed. Paraaortic LND is performed at the attendings' discretion. The algorithm was retrospectively applied. Results From 9/2005 to 4/2011, 498 patients received a blue dye cervical injection for SLN mapping. At least one LN was removed in 95% of cases (474/498); at least one SLN was identified in 81% (401/498). SLN correctly diagnosed 40/47 patients with nodal metastases who had at least one SLN mapped, resulting in a 15% false-negative rate. After applying the algorithm, the false-negative rate dropped to 2%. Only one patient, whose LN spread would not have been caught by the algorithm, had an isolated positive right paraaortic LN with a negative ipsilateral SLN and pelvic LND. Conclusions Satisfactory SLN mapping in endometrial cancer requires adherence to a surgical SLN algorithm and goes beyond just the removal of blue SLNs. Removal of any suspicious node along with side-specific lymphadenectomy for failed mapping are an integral part of this algorithm. Further validation of the false-negative rate of this algorithm is necessary.
Asian American, Native Hawaiian, and Pacific Islander (AANHPI) patient populations are often defined as one monolithic group in medical research despite cultural, socioeconomic, and clinical ...heterogeneity. Although the general AANHPI population is underrepresented in reception of postmastectomy breast reconstruction, existing literature has not characterized the disaggregation of such rates for AANHPI ethnic subgroups.
Patients who underwent mastectomy were identified in the 2007 to 2020 registries within the Surveillance, Epidemiology and End Results database. Patients were stratified by race and ethnicity, and additional demographic and oncologic variables were collected. Multivariate binary logistic regression was conducted to assess for reception of postmastectomy immediate breast reconstruction (p < 0.05).
Among 33,422 AANHPI patients who underwent mastectomy, South Asian patients were associated with the highest breast reconstruction rates (33%) and Melanesians with the lowest (15%). Overall, AANHPI patients were associated with a lower breast reconstruction rate than non-Hispanic Whites (27% vs. 35%; p < 0.001). This difference increased from 6.4% in 2007 to 10% in 2020. After controlling for demographic and oncologic covariates, all AANHPI ethnic subgroups predicted a lower likelihood of breast reconstruction than non-Hispanic Whites (p < 0.001). Odds ratios for reconstruction ranged from 0.17 95% confidence interval (95% CI), 0.11–0.27 for Melanesian patients to 0.45 (95% CI, 0.42–0.48) for South Asian patients.
Disparities in the receipt of immediate breast reconstruction exist within the AANHPI patient population in the United States. This analysis supported the need for disaggregation in plastic surgery research for improved knowledge and targeted interventions.
Asian patient populations continue to be underrepresented in both plastic surgery research and rates of breast reconstruction. Better elucidation of reconstruction in Asian women may help guide ...patient-directed counseling. This study investigates the differential effect of body mass index (BMI), a well-known risk factor, for Asian patients in outcomes after breast reconstruction.
Asian and White breast reconstruction patients were identified by CPT code in the National Surgical Quality Improvement Program. Within each cohort, BMI was converted into percentile ranks for standardized comparisons between cohorts. The effects of BMI on occurrence of complications for Asian and White patients were then quantified with multivariate logistic regression models.
The final cohort included 86,514 White patients and 4813 Asian patients, of which 9876 (11%) and 424 (8.8%) experienced at least one postoperative complication. The average BMI of White patients who experienced complications was 29.2 ± 6.3 kg/m2, a higher average than that of Asian patients, 25.6 ± 4.8 kg/m2. Higher BMI percentile was a significant predictor of increased risk of complications in White patients (OR: 1.005, 95% CI: 1.004–1.006, p < 0.001). In Asian patients, however, BMI percentile was not a significant predictor of postoperative complications (OR: 1.001, 95% CI: 0.997–1.005, p = 0.62). BMI percentile significantly predicted risk of unplanned reoperation in both cohorts (p < 0.001 and p = 0.029, respectively).
Whereas BMI is a direct predictor of complications in White populations, this effect is held more inconsistently for Asian patients. Such trends can guide more informed interpretations of BMI in current risk algorithms.
Efforts are underway for development of crops with improved levels of provitamin A carotenoids to help combat dietary vitamin A deficiency. As a global staple crop with considerable variation in ...kernel carotenoid composition, maize (Zea mays L.) could have a widespread impact. We performed a genome-wide association study (GWAS) of quantified seed carotenoids across a panel of maize inbreds ranging from light yellow to dark orange in grain color to identify some of the key genes controlling maize grain carotenoid composition. Significant associations at the genome-wide level were detected within the coding regions of zep1 and lut1, carotenoid biosynthetic genes not previously shown to impact grain carotenoid composition in association studies, as well as within previously associated lcyE and crtRB1 genes. We leveraged existing biochemical and genomic information to identify 58 a priori candidate genes relevant to the biosynthesis and retention of carotenoids in maize to test in a pathway-level analysis. This revealed dxs2 and lut5, genes not previously associated with kernel carotenoids. In genomic prediction models, use of markers that targeted a small set of quantitative trait loci associated with carotenoid levels in prior linkage studies were as effective as genome-wide markers for predicting carotenoid traits. Based on GWAS, pathway-level analysis, and genomic prediction studies, we outline a flexible strategy involving use of a small number of genes that can be selected for rapid conversion of elite white grain germplasm, with minimal amounts of carotenoids, to orange grain versions containing high levels of provitamin A.
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