Dual-Channel-Ion Conductor Membrane for Low-Energy Lithium Extraction.

The development of energy-efficient and environmentally friendly lithium extraction techniques is essential to meet the growing global demand for lithium-ion batteries. In this work, a dual-channel ion conductor membrane was designed for a concentration-driven lithium-selective ion diffusion process. The membrane was based on a porous lithium-ion conductor, and its pores were modified with an anion-exchange polymer. Thus, the sintered lithium-ion conductors provided highly selective cation transport channels, and the functionalized nanopores with positive charges enabled the complementary permeation of anions to balance the transmembrane charges. As a result, the dual-channel membrane realized an ultrahigh Li+/Na+ selectivity of ∼1389 with a competitive Li+ flux of 21.6 mmol·m-2·h-1 in a diffusion process of the LiCl/NaCl binary solution, which was capable of further maintaining the high selectivity over 7 days of testing. Therefore, this work demonstrates the great potential of the dual-channel membrane design for high-performing lithium extraction from aqueous resources with low energy consumption and minimal environmental impact.

Thermoresponsive Poly(N-isopropylacrylamide) Grafted from Cellulose Nanofibers via Silver-Promoted Decarboxylative Radical Polymerization.

A family of thermoresponsive poly(N-isopropylacrylamide) [PNIPAM]-grafted cellulose nanofibers (CNFs) was synthesized via a novel silver-promoted decarboxylative polymerization approach. This method relies on the oxidative decarboxylation of carboxylic acid groups to initiate free radicals on the surface of CNFs. The polymerization reaction employs relatively mild reaction conditions and can be performed in a one-step, one-pot fashion. This rapid reaction forms a C─C bond between CNF and PNIPAM, along with the formation of free polymer in solution. The degree of functionalization (DF) and the amount of PNIPAM grafted can be controlled by the Ag concentration in the reaction. Similar to native bulk PNIPAM, PNIPAM-grafted CNFs (PNIPAM-g-CNFs) show remarkable thermoresponsive properties, albeit exhibiting a slight hysteresis between the heating and cooling stages. Grafting PNIPAM from CNFs changes its cloud point from about 32 to 36 °C, influenced by the hydrophilic nature of CNFs. Unlike physical blending, covalently tethering PNIPAM transforms the originally inert CNFs into thermosensitive biomaterials. The Ag concentration used does not significantly change the cloud point of PNIPAM-g-CNFs, while the cloud point slightly decreases with fiber concentration. Rheological studies demonstrated the sol-gel transition of PNIPAM-g-CNFs and revealed that the storage modulus (G') above cloud point increases with the amount of PNIPAM grafted. The novel chemistry developed paves the way for the polymerization of any vinyl monomer from the surface of CNFs and carbohydrates. This study validates a novel approach to graft PNIPAM from CNFs for the synthesis of new thermoresponsive and transparent hydrogels for a wide range of applications.

A Phase II Trial of Alisertib (MLN8237) in Salvage Malignant Mesothelioma.

LESSONS LEARNED: Treatment with the Aurora kinase A inhibitor yields often durable disease control, but limited tumor regression, in heavily pretreated patients with unresectable malignant pleural or peritoneal mesothelioma. In a limited sample size, MYC copy-number gain or gene amplification, a candidate predictive biomarker for alisertib, did not correlate with improved response numbers or patient outcomes. BACKGROUND: Malignant mesothelioma is an aggressive disease for which few effective therapies are available. The Aurora family kinases are critical for mitotic fidelity and highly expressed in mesothelioma, wherein their inhibition leads to growth arrest in vitro. We evaluated the efficacy of alisertib, an Aurora A kinase inhibitor, in relapsed malignant mesothelioma. METHODS: Twenty-six patients with previously treated, unresectable pleural or peritoneal mesothelioma were enrolled on a single-arm, single-institution phase II trial of alisertib at a dosage of 50 mg twice daily for 7 of every 21 days. The primary endpoint was 4-month disease control rate. Secondary endpoints included overall response rate, progression free survival, overall survival, safety/toxicity, and correlation of endpoints with MYC copy number. RESULTS: Of the 25 evaluable patients treated on study, 8 (32%) experienced 4-month disease control, surpassing the futility endpoint. There were no confirmed partial or complete responses. Median progression-free and overall survival were 2.8 months and 6.3 months, respectively. No associations between MYC copy number and outcomes were observed. CONCLUSION: Alisertib has modest activity in this unselected malignant mesothelioma population. Several patients achieved durable disease control. Although the study did meet its prespecified futility endpoint, the sponsor elected to close the trial at the interim analysis.

Development of a Paper-Based Microfluidic System for a Continuous High-Flow-Rate Fluid Manipulation.

The current study describes the development of a disposable paper-based microfluidic system, which unlike its predecessors that are only capable of processing a small amount of fluid, can continuously process the fluid at a high flow rate of up to 1.5 mL/min. The fabrication procedure was clean-room-free and robust, involving the use of a CO2 laser to engrave the microchannels on a paper substrate, followed by alkenyl ketene dimer treatment to hydrophobize the paper and lamination. The microchannel down to a minimum depth of ∼80 µm with an average roughness of ∼8 µm was engraved on the substrate. As a proof of concept, the applicability of this system to enrich the microparticles based on the inertial focusing mechanism was tested. This new generation of paper-based microfluidic system can be potentially used for the diagnostic applications where the analyte is low in quantity and processing a large volume of fluid sample is required.

Vertically Aligned Gold Nanowires as Stretchable and Wearable Epidermal Ion-Selective Electrode for Noninvasive Multiplexed Sweat Analysis.

The noninvasive continuous analysis of human sweat is of great significance for improved healthcare diagnostics and treatment in the future, for which a wearable potentiometry-based ion-selective electrode (ISE) has attracted increasing attention, particularly involving ion detection. Note that traditional solid-state ISE electrodes are rigid ion-to-electron transducers that are not conformal to soft human skin and cannot function under stretched states. Here, we demonstrated that vertically aligned mushroom-like gold nanowires (v-AuNW) could serve as stretchable and wearable ion-to-electron transducers for multiplexed, in situ potentiometric analysis of pH, Na+, and K+ in sweat. By modifying v-AuNW electrodes with polyaniline, Na ionophore X, and a valinomycin-based selective membrane, we could specifically detect pH, Na+, and K+, respectively, with high selectivity, reproducibility, and stability. Importantly, the electrochemical performance could be maintained even under 30% strain and during stretch-release cycles without the need of extrinsic structural design. Furthermore, our stretchable v-AuNW ISEs could be seamlessly integrated with a flexible printed circuit board, enabling wireless on-body detection of pH, Na+, and K+ with fast response and negligible cross-talk, indicating considerable promise for noninvasive wearable sweat analysis.

Applying Artificial Intelligence to Address the Knowledge Gaps in Cancer Care.

BACKGROUND: Rapid advances in science challenge the timely adoption of evidence-based care in community settings. To bridge the gap between what is possible and what is practiced, we researched approaches to developing an artificial intelligence (AI) application that can provide real-time patient-specific decision support. MATERIALS AND METHODS: The Oncology Expert Advisor (OEA) was designed to simulate peer-to-peer consultation with three core functions: patient history summarization, treatment options recommendation, and management advisory. Machine-learning algorithms were trained to construct a dynamic summary of patients cancer history and to suggest approved therapy or investigative trial options. All patient data used were retrospectively accrued. Ground truth was established for approximately 1,000 unique patients. The full Medline database of more than 23 million published abstracts was used as the literature corpus. RESULTS: OEA's accuracies of searching disparate sources within electronic medical records to extract complex clinical concepts from unstructured text documents varied, with F1 scores of 90%-96% for non-time-dependent concepts (e.g., diagnosis) and F1 scores of 63%-65% for time-dependent concepts (e.g., therapy history timeline). Based on constructed patient profiles, OEA suggests approved therapy options linked to supporting evidence (99.9% recall; 88% precision), and screens for eligible clinical trials on ClinicalTrials.gov (97.9% recall; 96.9% precision). CONCLUSION: Our results demonstrated technical feasibility of an AI-powered application to construct longitudinal patient profiles in context and to suggest evidence-based treatment and trial options. Our experience highlighted the necessity of collaboration across clinical and AI domains, and the requirement of clinical expertise throughout the process, from design to training to testing. IMPLICATIONS FOR PRACTICE: Artificial intelligence (AI)-powered digital advisors such as the Oncology Expert Advisor have the potential to augment the capacity and update the knowledge base of practicing oncologists. By constructing dynamic patient profiles from disparate data sources and organizing and vetting vast literature for relevance to a specific patient, such AI applications could empower oncologists to consider all therapy options based on the latest scientific evidence for their patients, and help them spend less time on information "hunting and gathering" and more time with the patients. However, realization of this will require not only AI technology maturation but also active participation and leadership by clincial experts.

Randomized-controlled phase II trial of salvage chemotherapy after immunization with a TP53-transfected dendritic cell-based vaccine (Ad.p53-DC) in patients with recurrent small cell lung cancer.

Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Vaccine was administered every 2 weeks (3 times), and all patients were to receive paclitaxel at progression. Our primary endpoint was overall response rate (ORR) to paclitaxel. The study was not designed to detect overall response rate differences between arms. Of 69 patients enrolled (performance status 0/1, median age 62 years), 55 were treated in stage 1 (18 in arm A, 20 in arm B, and 17 in arm C) and 14 in stage 2 (arm C only), per 2-stage Simon Minimax design. The vaccine was safe, with mostly grade 1/2 toxicities, although 1 arm-B patient experienced grade 3 fatigue and 8 arm-C patients experienced grade 3 toxicities. Positive immune responses were obtained in 20% of arm B (95% confidence interval [CI], 5.3-48.6) and 43.3% of arm C (95% CI 23.9-65.1). The ORRs to the second-line chemotherapy (including paclitaxel) were 15.4% (95% CI 2.7-46.3), 16.7% (95% CI 2.9-49.1), and 23.8% (95% CI 9.1-47.5) for arms A, B, and C, with no survival differences between arms. Although our vaccine failed to improve ORRs to the second-line chemotherapy, its safety profile and therapeutic immune potential remain. Combinations with the other immunotherapeutic agents are reasonable options.

Assessment of baseline symptom burden in treatment-naïve patients with lung cancer: an observational study.

BACKGROUND: Patients with newly diagnosed lung cancer who have not yet begun treatment may already be experiencing major symptoms produced by their disease. Understanding the symptomatic effects of cancer treatment requires knowledge of pretreatment symptoms (both severity and interference with daily activities). We assessed pretreatment symptom severity, interference, and quality of life (QOL) in treatment-naïve patients with lung cancer and report factors that correlated with symptom severity. METHODS: This was a retrospective analysis of data collected at initial intake. Symptoms/interference were rated on the MD Anderson Symptom Inventory (MDASI) between 30 days prediagnosis and 45 days postdiagnosis. We examined symptom severity by disease stage and differences in severity by histology. Linear regression analyses identified significant predictors of severe pain and dyspnea. RESULTS: Of 460 eligible patients, 256 (62%) had adenocarcinoma, 30 (7%) had small cell carcinoma, and 100 (24%) had squamous cell carcinoma; > 30% reported moderate-to-severe (rated ≥ 5, 0-10 scale) pretreatment symptoms. The most-severe were fatigue, disturbed sleep, distress, pain, dyspnea, sadness, and drowsiness. Symptoms affected work, enjoyment of life, and general activity (interference) and physical well-being (QOL) the most. Patients with advanced disease (n = 289, 63%) had more-severe symptoms. Cancer stage was associated with pain severity; both histology and cancer stage were associated with severe dyspnea. CONCLUSION: One third of lung cancer patients were symptomatic at initial presentation. Quantification of pretreatment symptom burden can inform patient-specific palliative therapy and differentiate disease-related symptoms from treatment-related toxicities. Poorly controlled symptoms could negatively affect treatment adherence and therapeutic outcomes.

Long-term safety and survival with gefitinib in select patients with advanced non-small cell lung cancer: Results from the US IRESSA Clinical Access Program (ICAP).

BACKGROUND: This is the first report of long-term (>10 years) safety, tolerability, and survival data on patients with non-small cell lung cancer (NSCLC) who received treatment with gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. METHODS: Patients with advanced NSCLC (N = 191) who entered the IRESSA Clinical Access Program (ICAP) (June 2011 to January 2013) and had previously obtained a clinical benefit from gefitinib therapy (including patients who had received gefitinib since 2001) were analyzed for adverse events (AEs). A subset of patients (n = 79) underwent retrospective chart review to capture demographic, safety, and survival data. RESULTS: Seventy-five of 191 patients (39%) remained on long-term gefitinib therapy as of September 2016. Overall, serious AEs (SAEs) were reported in 64 patients (34%), the majority of which were attributed to underlying disease or comorbidities; only 3 patients (1.6%) had SAEs that were considered as possibly gefitinib-related. In the retrospective chart review cohort, 70% of patients were women; 58% were former smokers, and 30% were never-smokers; 56% were diagnosed with adenocarcinoma, and 13% were diagnosed with squamous carcinoma. Although EGFR mutational status was tested in only 17 patients (22%), it was assumed that most tumors were EGFR-mutation-positive. The median duration of gefitinib therapy was 11.1 years (7.8 years before and 3.5 years during ICAP), with 10-year and 15-year survival rates of 86% and 59%, respectively, from the initiation of therapy. CONCLUSIONS: A subset of long-term NSCLC survivors who were receiving gefitinib had an excellent long-term safety profile. Although it is assumed that most of these patients' tumors harbor EGFR mutations, molecular studies of available tumor specimens are planned to uncover the features that predict long-term survival. Cancer 2018;124:2407-14. © 2018 American Cancer Society.

Vertical Gold Nanowires Stretchable Electrochemical Electrodes.

Conventional electrodes produced from gold or glassy carbon are outstanding electrochemical platforms for biosensing applications due to their chemical inertness and wide electrochemical window, but are intrinsically rigid and planar in nature. Hence, it is challenging to seamlessly integrate them with soft and curvilinear biological tissues for real-time wearable or implantable electronics. In this work, we demonstrate that vertically gold nanowires (v-AuNWs) possess an enokitake-like structure, with the nanoparticle (head) on one side and nanowires (tail) on the opposite side of the structure, and can serve as intrinsically stretchable, electrochemical electrodes due to the stronger nanowire-elastomer bonding forces preventing from interfacial delamination under strains. The exposed head side of the electrode comprising v-AuNWs can achieve a detection limit for H2O2 of 80 µM, with a linear range of 0.2-10.4 mM at 20% strain, with a reasonably high sensitivity using chronoamperometry. This excellent electrochemical performance in the elongated state, in conjunction with low-cost wet-chemistry fabrication, demonstrates that v-AuNWs electrodes may become a next-generation sensing platform for conformally integrated, in vivo biodiagnostics.

Atomistic insights into the adsorption and stimuli-responsive behavior of poly(N-isopropylacrylamide)-graphene hybrid systems.

Non-covalent functionalization of graphene materials with responsive polymers is a promising approach for synthesizing new, hybrid composites with improved dispersibility and functional properties. However, the interplay between various components of the hybrid systems, their structural configurations, and stimuli-responsive behavior are not yet well understood at the atomic level. Here, we investigate the temperature-responsive behavior of physisorbed poly(N-isopropylacrylamide) (PNIPAM) on to graphene (G) and graphene oxide (GO) sheets in aqueous solution using large scale molecular dynamics simulations. It was observed that PNIPAM can be spontaneously anchored to the surfaces of both G and GO at 290 K with a macromolecular coil shape. However, the configuration of PNIPAM on G is markedly different in comparison with that on GO, leading to its distinct thermoresponsive behavior. Specifically, the adsorption on G gives rise to an increase in the temperature of the coil-to-globule transition when compared to the native polymer, the origin of which can be interpreted in terms of the interactions and the solvation behavior. The results obtained here are of significance to the design and manipulation of graphene-based stimuli-responsive hybrid systems with optimal functional properties.

Functionalized Boron Nitride Nanosheets: A Thermally Rearranged Polymer Nanocomposite Membrane for Hydrogen Separation.

Amino functionalized boron nitride nanosheets (FBN) were incorporated into a crosslinked, thermally rearranged polyimide (XTR) to fabricate FBN-XTR nanocomposite membrane. The FBN-XTR membrane exhibited a small decrease in H2 permeability but demonstrated a remarkably increased H2 gas selectivity over other gases, compared with XTR. The XTR membrane heat-treated at 425 °C had a H2 permeability of 210 Barrers and a H2 /CH4 separation factor of 24.1, whereas the nanocomposite membrane with 1 wt % FBN exhibited a H2 permeability of 110 Barrers and H2 /CH4 separation factor of 275, an order of magnitude greater. At 1 wt % FBN loading, the FBN-XTR membrane showed three times higher tensile strength and 60 % higher elongation than pristine XTR membrane. In addition, FBN-XTR was found to be able to be readily processed into thin-film membranes for practical H2 separation applications.

Impact of the timing of hepatitis B virus identification and anti-hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy.

BACKGROUND: Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]-positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg-negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. METHODS: Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. RESULTS: There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. CONCLUSIONS: Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients receiving chemotherapy. Cancer 2017;123:3367-76. © 2017 American Cancer Society.

Renewable Green Platform Chemicals for Polymers.

n/a.

Robust Thermoresponsive Polymer Composite Membrane with Switchable Superhydrophilicity and Superhydrophobicity for Efficient Oil-Water Separation.

Herein, we report for the first time on the fabrication of a robust, thermoresponsive polymer membrane produced by the combination of an elastic polyurethane (TPU) microfiber web and poly(N-isopropylacrylamide) (PNIPAM). PNIPAM hydrogel is evenly coated on the surface of TPU microfibers, and thus, the wettability of TPU-PNIPAM membrane is amplified by taking advantage of the hierarchical structure and increased surface roughness. The TPU-PNIPAM membrane possesses switchable superhydrophilicity and superhydrophobicity as the temperature of membrane changes from 25 to 45 °C. The composite membrane is shown successfully able to separate a 1 wt % oil-in-water emulsion and 1 wt % water-in-oil emulsion at 25 and 45 °C, respectively, with a high separation efficiency of ≥99.26%. Furthermore, the composite membranes show excellent mechanical properties, and they are highly flexible and mechanically tough. The smart composite membranes reported here have shown great potential for further development for practical high-efficiency oil-water separations.

Characterization, localization and temporal expression of crustacean hyperglycemic hormone (CHH) in the behaviorally rhythmic peracarid crustaceans, Eurydice pulchra (Leach) and Talitrus saltator (Montagu).

Crustacean hyperglycemic hormone (CHH) has been extensively studied in decapod crustaceans where it is known to exert pleiotropic effects, including regulation of blood glucose levels. Hyperglycemia in decapods seems to be temporally gated to coincide with periods of activity, under circadian clock control. Here, we used gene cloning, in situ hybridization and immunohistochemistry to describe the characterization and localization of CHH in two peracarid crustaceans, Eurydice pulchra and Talitrus saltator. We also exploited the robust behavioral rhythmicity of these species to test the hypothesis that CHH mRNA expression would resonate with their circatidal (12.4h) and circadian (24h) behavioral phenotypes. We show that both species express a single CHH transcript in the cerebral ganglia, encoding peptides featuring all expected, conserved characteristics of other CHHs. E. pulchra preproCHH is an amidated 73 amino acid peptide N-terminally flanked by a short, 18 amino acid precursor related peptide (CPRP) whilst the T. saltator prohormone is also amidated but 72 amino acids in length and has a 56 residue CPRP. The localization of both was mapped by immunohistochemistry to the protocerebrum with axon tracts leading to the sinus gland and into the tritocerebrum, with striking similarities to terrestrial isopod species. We substantiated the cellular position of CHH immunoreactive cells by in situ hybridization. Although both species showed robust activity rhythms, neither exhibited rhythmic transcriptional activity indicating that CHH transcription is not likely to be under clock control. These data make a contribution to the inventory of CHHs that is currently lacking for non-decapod species.

A Versatile Iron-Tannin-Framework Ink Coating Strategy to Fabricate Biomass-Derived Iron Carbide/Fe-N-Carbon Catalysts for Efficient Oxygen Reduction.

The conversion of biomass into valuable carbon composites as efficient non-precious metal oxygen-reduction electrocatalysts is attractive for the development of commercially viable polymer electrolyte membrane fuel-cell technology. Herein, a versatile iron-tannin-framework ink coating strategy is developed to fabricate cellulose-derived Fe3 C/Fe-N-C catalysts using commercial filter paper, tissue, or cotton as a carbon source, an iron-tannin framework as an iron source, and dicyandiamide as a nitrogen source. The oxygen reduction performance of the resultant Fe3C/Fe-N-C catalysts shows a high onset potential (i.e. 0.98 V vs the reversible hydrogen electrode (RHE)), and large kinetic current density normalized to both geometric electrode area and mass of catalysts (6.4 mA cm(-2) and 32 mA mg(-1) at 0.80 V vs RHE) in alkaline condition. This method can even be used to prepare efficient catalysts using waste carbon sources, such as used polyurethane foam.

A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin.

PURPOSE: LY2090314 (LY) is a glycogen synthase kinase 3 inhibitor with preclinical efficacy in xenograft models when combined with platinum regimens. A first-in-human phase 1 dose-escalation study evaluated the combination of LY with pemetrexed/carboplatin. PATIENTS AND METHODS: Forty-one patients with advanced solid tumors received single-dose LY monotherapy lead-in and 37 patients received LY (10-120 mg) plus pemetrexed/carboplatin (500 mg/m(2) and 5-6 AUC, respectively) across 8 dose levels every 21 days. Primary objective was maximum tolerated dose (MTD) determination; secondary endpoints included safety, antitumor activity, pharmacokinetics, and beta-catenin pharmacodynamics. RESULTS: MTD of LY with pemetrexed/carboplatin was 40 mg. Eleven dose-limiting toxicities (DLTs) occurred in ten patients. DLTs during LY monotherapy occurred at ≥ 40 mg: grade 2 visual disturbance (n = 1) and grade 3/4 peri-infusional thoracic pain during or shortly post infusion (n = 4; chest, upper abdominal, and back pain). Ranitidine was added after de-escalation to 80 mg LY to minimize peri-infusional thoracic pain. Following LY with pemetrexed/carboplatin therapy, DLTs included grade 3/4 thrombocytopenia (n = 4) and grade 4 neutropenia (n = 1). Best overall response by RECIST included 5 confirmed partial responses (non-small cell lung cancer [n = 3], mesothelioma, and breast cancer) and 19 patients having stable disease. Systemic LY exposure was approximately linear over dose range studied. Transient upregulation of beta-catenin measured in peripheral blood mononuclear cells (PBMCs) occurred at 40 mg LY. CONCLUSIONS: The initial safety profile of LY2090314 was established. MTD LY dose with pemetrexed/carboplatin is 40 mg IV every 3 weeks plus ranitidine. Efficacy of LY plus pemetrexed/carboplatin requires confirmation in randomized trials.

Photodegradable Gelatin-Based Hydrogels Prepared by Bioorthogonal Click Chemistry for Cell Encapsulation and Release.

In this study, we present a method for the fabrication of in situ forming gelatin and poly(ethylene glycol)-based hydrogels utilizing bioorthogonal, strain-promoted alkyne-azide cycloaddition as the cross-linking reaction. By incorporating nitrobenzyl moieties within the network structure, these hydrogels can be designed to be degradable upon irradiation with low intensity UV light, allowing precise photopatterning. Fibroblast cells encapsulated within these hydrogels were viable at 14 days and could be readily harvested using a light trigger. Potential applications of this new class of injectable hydrogel include its use as a 3D culturing platform that allows the capture and release of cells, as well as light-triggered cell delivery in regenerative medicine.

Biodegradability of Poly-3-hydroxybutyrate/Bacterial Cellulose Composites under Aerobic Conditions, Measured via Evolution of Carbon Dioxide and Spectroscopic and Diffraction Methods.

Poly-3-hydroxybutyrate (PHB) and bacterial cellulose (BC) are both natural polymeric materials that have the potential to replace traditional, nonrenewable polymers. In particular, the nanofibrillar form of bacterial cellulose makes it an effective reinforcement for PHB. Neat PHB, bacterial cellulose, and a composite of PHB/BC produced with 10 wt % cellulose were composted under accelerated aerobic test conditions, with biodegradability measured by the carbon dioxide evolution method, in conjunction with spectroscopic and diffraction methods to assess crystallinity changes during the biodegradation process. The PHB/BC composite biodegraded at a greater rate and extent than that of PHB alone, reaching 80% degradation after 30 days, whereas PHB did not reach this level of degradation until close to 50 days of composting. The relative crystallinity of PHB and PHB in the PHB/BC composite was found to increase in the initial weeks of degradation, with degradation occurring primarily in the amorphous region of the material and some recrystallization of the amorphous PHB. Small angle X-ray scattering indicates that the change in PHB crystallinity is accompanied by a change in morphology of semicrystalline lamellae. The increased rate of biodegradability suggests that these materials could be applicable to single-use applications and could rapidly biodegrade in compost on disposal.